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A detailed description of the pharmacological treatments used in Alzheimer’s disease

Introduction

The nervous system is involved in the transmission of signals for communication and for coordination of body systems. The principle cell of the nervous system is a neuron, the neuron components are a cell body, dendrites, axon, synaptic terminals and myelin sheath (not always). The cell body component of the neuron integrates signals and coordinates metabolic activities. Dendrites are the branched projections of a neuron that act to conduct the electrochemical stimulation. The axon in the neuron conducts the signal and the synaptic terminals transmit the signals. The myelin sheath is the coating on some neurons that that acts as an insulator to speed the conduction of nerve impulses, usually around only the axon of a neuron.

The transmission of a nerve impulse along a neuron from one end to the other occurs as a result of chemical changes across the membrane of the neuron. The membrane of an unstimulated neuron is polarized—that is, there is a difference in electrical charge between the outside and inside of the membrane. The inside is negative with respect to the outside. Such polarization is established by maintaining an excess of sodium ions (Na+) on the outside and an excess of potassium ions (K+) on the inside. Na+/K+ pumps in the membrane actively restore the ions to the appropriate side.

Other ions, such as large, negatively charged proteins and nucleic acids, reside within the cell. It is these large, negatively charged ions that contribute to the overall negative charge on the inside of the cell membrane as compared to the outside. In addition to crossing the membrane through leakage channels, ions may also cross through gated channels. Gated channels open in response to neurotransmitters, changes in membrane potential, or other stimuli. The following events characterize the transmission of a nerve impulse.

Resting potential: The resting potential describes the unstimulated, polarized state of a neuron.

Graded potential: A graded potential is a change in the resting potential. A graded potential occurs when the stimulus causes Na+ or K+ gated channels to open. Na+ channels open, positive sodium ions enter, and the membrane depolarizes (becomes more positive).

If the stimulus opens K+ channels, then positive potassium ions exit across the membrane and the membrane hyperpolarizes (becomes more negative).

Action potential: An action potential is capable of traveling long distances. If a depolarizing graded potential is sufficiently large, Na+ channels in the trigger zone open. In response, Na+ on the outside of the membrane becomes depolarized (as in a graded potential).

Repolarization: In response to the inflow of Na+, K+ channels open, this time allowing K+ on the inside to rush out of the cell. The movement of K+ out of the cell causes repolarization by restoring the original membrane polarization. Soon after the K+ gates open, the Na+ gates close.

Hyperpolarization: This is when K+ channels closes and more K+ has moved out of the cell. As a result, the membrane becomes hyperpolarized.

Refractory period: The membrane is polarized, but the Na+ and K+ are on the wrong sides of the membrane. During this refractory period, the axon will not respond to a new stimulus. To re-establish the original distribution of these ions, the Na+ and K+ are returned to their resting potential location by Na+/K+ pumps in the cell membrane. Once these ions are returned to their resting potential the neuron is ready for another stimulus.

Transmission of Nerve Impulses between Neurons:

The nerve impulse (action potential) travels down the presynaptic axon towards the synapse, where it activates voltage-gated calcium channels leading to calcium influx, which triggers the simultaneous release of neurotransmitter molecules from many synaptic vesicles by fusing the membranes of the vesicles to that of the nerve terminal. The neurotransmitter molecules diffuse across the synaptic cleft, bind briefly to receptors on the postsynaptic neuron to activate them, causing physiological responses that may be excitatory or inhibitory depending on the receptor.

The central nervous system (CNS) is that part of the nervous system that consists of the brain and spinal cord. The central nervous system is one of the two major divisions of the nervous system. The other is the peripheral nervous system (PNS) which is outside the brain and spinal cord.

The peripheral nervous system (PNS) connects the central nervous system (CNS) to sensory organs (such as the eye and ear), other organs of the body, muscles, blood vessels and glands.

The hippocampus is one of the first regions of the brain to suffer damage; memory problems and disorientation appear among the first symptoms. Damage to the hippocampus can also result from oxygen starvation (hypoxia), encephalitis, or medial temporal lobe epilepsy. People with extensive, bilateral hippocampal damage may experience anterograde amnesia—the inability to form or retain new memories.

Cholinesterase is a family of enzymes that catalyze the hydrolysis of the neurotransmitter acetylcholine into choline and acetic acid, a reaction necessary to allow a cholinergic neuron to return to its resting state after activation.

Cholinesterase inhibitors work by increasing levels of acetylcholine, a chemical messenger involved in memory, judgment and other thought processes. Certain brain cells release acetylcholine, which helps deliver messages to other cells. After a message reaches the receiving cell, various other chemicals, including an enzyme called acetylcholinesterase, break acetylcholine down so it can be recycled.

Alzheimer’s disease (AD) is a slowly progressive disease of the brain that is characterized by impairment of memory and eventually by disturbances in reasoning, planning, language, and perception. Alzheimer’s disease is a result from an increase in the production of beta-amyloid protein in the brain that leads to nerve cell death. The only way to know for certain that someone has AD is to examine a sample of their brain tissue after death. The following changes are more common in the brain tissue of people with AD: Neurofibrillary tangles which are twisted fragments of protein within nerve cells that clog up the cell. Another change which is common in brain tissue of a patient with AD is neuritic plaques (containing beta-amyloid protein) mentioned above. This results in abnormal clusters of dead and dying nerve cells, other brain cells, and aberrant protein deposits. When nerve cells are destroyed, there is a decrease in the chemicals/electrical signal that helps nerve cells send messages to one another, which are called neurotransmitters. As a result, areas of the brain that normally work together become disconnected.

The probability of having Alzheimer’s disease increases substantially after the age of 70 and may affect around 50% of persons over the age of 85. However Alzheimer’s disease is not a normal part of aging and is not something that certainly happens in later life, many people live to over 100 years of age and never develop Alzheimer’s disease.

Fig 1 (http://www.alz.org/brain/images/09a.jpg)

In fig 1 above is a view of how massive cell loss changes the whole brain in advanced Alzheimer’s disease. This illustration shows a crosswise “slice” through the middle of the brain between the ears. In the Alzheimer’s brain, the cortex shrivels up, damaging areas involved in thinking, planning and remembering. Shrinkage is especially severe in the hippocampus, an area of the cortex that plays a key role in formation of new memories. The ventricles spaces grow larger.

The risks factors implicated in Alzheimer’s disease are age, ApoE4, Down’s syndrome, head injury, low education and also family history i.e. genes. The main risk factor for Alzheimer’s disease is increased age. As a population ages, the frequency of Alzheimer’s disease continues to increase. Studies show that 10% of people over 65 years of age and 50% of those over 85 years of age have Alzheimer’s disease. There are also genetic risk factors for Alzheimer’s disease. Most patients develop Alzheimer’s disease after age 70. However, 2%-5% of patients develop the disease in the fourth or fifth decade of life (40s or 50s). At least half of these early onset patients have inherited gene mutations associated with their Alzheimer’s disease. Also a child of a patient with early onset Alzheimer’s disease who has one of these gene mutations has a 50% risk of developing Alzheimer’s disease. Other risk factors for Alzheimer’s disease include high blood pressure (hypertension), coronary artery disease, diabetes, and possibly elevated blood cholesterol. Individuals who have completed less than eight years of education also have an increased risk for Alzheimer’s disease. These factors increase the risk of Alzheimer’s disease, but this does not mean Alzheimer’s disease is necessarily expected in persons with these factors.

The onset of Alzheimer’s disease is usually gradual, and it is slowly progressive. Problems of memory, particularly for recent events (short-term memory) are common early in the course of Alzheimer’s disease. Mild personality changes, such as less spontaneity, apathy, and a tendency to withdraw from social interactions, may occur early in the illness. As the disease progresses, problems in abstract thinking and in other intellectual functions develop. Further disturbances in behaviour and appearance may also be seen at this point, such as agitation, irritability and a deteriorating ability to dress appropriately. Later in the course of the disorder, affected individuals may become confused or disoriented. Eventually, patients will be unable to engage in conversation, become erratic in mood, uncooperative, and lose bladder and bowel control. In late stages of the disease, persons may become totally incapable of caring for themselves, and a result of this could be death. Those who develop the disorder later in life more often die from other illnesses (i.e. heart disease).

Fig 2 – Deaths from Alzheimer’s disease: (http://www.alz.org/downloads/Facts_Figures_2011.pdf)

From Fig 2 Alzheimer’s disease is the sixth-leading cause of death in the country and the only cause of death among the top 10 in the United States that cannot be prevented, cured or even slowed. From the data in the graph, death rates have declined for most major diseases while deaths from Alzheimer’s disease have risen 66 percent during the same period.

Unfortunately, there is no cure for AD. However there are goals in treating AD, these goals are to slow the progression of the disease (although this is difficult to do), manage behaviour problems, confusion, sleep problems, and agitation, modify the home environment and support family members and other caregivers.

Cholinesterase blockers are one of the main treatments of AD. Cholinesterase inhibitors are prescribed to treat symptoms related to memory, thinking, language, judgment and other thought processes. The different cholinesterase inhibitors are Donepezil, Rivastigmine, Galanthamine, Tacrine and Memantine. The three main drugs currently licensed for the treatment of AD are Donepezil, Rivastigmine and Galanthamine.

Donepezil is the generic name and the brand name is Aricept. Donepezil is approved at all stages of Alzheimer’s disease. However the side effects of this drug are nausea, vomiting, loss of appetite and increased frequency of bowel movements. Galanthamine, brand name Razadyne, is approved for the mild to moderate stages of AD. The side effects of Galanthamine are nausea, vomiting, loss of appetite and increased frequency of bowel movements. Memantine (brand name Namenda), is approved for moderate to severe stages of AD, The side effects of this drug are headache, constipation, confusion and dizziness. Rivastigmine (brand name Exelon), approved for mild to moderate Alzheimer’s, the side effects of Rivastigmine are nausea, vomiting, loss of appetite and increased frequency of bowel movements. Tacrine (also known as Cognex), this was the first cholinesterase inhibitor and was approved in 1993 but is rarely prescribed today; this is because of associated side effects which include possible liver damage.

Cholinesterase inhibitors work by increasing levels of acetylcholine, a chemical messenger involved in memory, judgment and other thought processes. Certain brain cells release acetylcholine, which helps deliver messages to other cells. After a message reaches the receiving cell, various other chemicals, including an enzyme called acetylcholinesterase, break acetylcholine down so it can be recycled.

But Alzheimer’s disease damages or destroys cells that produce and use acetylcholine, thereby reducing the amount available to carry messages. A cholinesterase inhibitor slows the breakdown of acetylcholine by blocking the activity of acetylcholinesterase. By maintaining acetylcholine levels, the drug may help compensate for the loss of functioning brain cells.

The benefits of cholinesterase inhibitors are that people taking the cholinesterase inhibitor medications performed better on memory and thinking tests than those taking a placebo, or inactive substance. In terms of overall effect, most experts believe cholinesterase inhibitors may delay or slow worsening of symptoms for about six months to a year; although some people may benefit more dramatically or for a longer time.

Namenda is approved to treat moderate-to-severe Alzheimer’s disease. Namenda works by a different mechanism than other Alzheimer’s treatments; it is thought to play a protective role in the brain by regulating the activity of a different brain chemical called glutamate. Glutamate also plays a role in learning and memory. Brain cells in people with Alzheimer’s disease release too much glutamate (Alzheimer’s Association 2007). Namenda helps regulate glutamate activity. Namenda works by blocking the receptors for the neurotransmitter glutamate. It is believed that glutamate plays an important role in the neural pathways associated with learning and memory. In brain disorders such as Alzheimer’s disease, overexcitation of neurons produced by abnormal levels of glutamate may be associated with neuronal cell dysfunction (resulting in cognitive and memory deficits) and eventual cell death (leading to deterioration and collapse of intellectual functioning). By selectively blocking a type of glutamate receptor (NMDA receptor) while allowing for normal neurotransmission, Namenda may help reduce the excitotoxic effects associated with abnormal transmission of glutamate. (psychatlanta.com)

Namenda may have increased benefit when used with Aricept, Exelon, Razadyne, or Cognex. Memantine, a voltagegated and uncompetitive NMDA antagonist with moderate affinity, can protect neurons from excitotoxicity. It was approved for treatment of the patients with moderate to severe AD. (Alzheimer’s Association 2007)

A growing body of evidence suggest that drugs indicated for other conditions may also possess preventive efficacy for AD. Among the most promising are antioxidants, nonsteroidal, statins, certain anti hypertensive agents, alcohol, fish oil and possibly estrogen. Antioxidants have been recommended for prevention of dementia. The use of natural antioxidants may inhibit damage to the muscarinic receptors caused by free radicals, possibly by preventing or treating AD. High dietary intake of vitamins C and E lower the risk of AD. Estrogen is a weak antioxidant, it is biologically plausible that hormone replacement therapy (HRT) could protect against AD (Zandi PP et al 2002). AD is more likely to develop in a person with atherosclerotic cerebrovascular disease (Postiglione 1995). Antiatheroscleotic pharmacotherapies are used to treat atherosclerotic cerebrovascular disease, which then prevents AD from occurring (John B et al 2004). Folic acid is a AD preventer and is effective against AD. Folic acid is effective because it reduces homocysteine concentration, increased levels of homocysteine concentration increases the risk of AD. Statins is very effective at reducing the risk of AD. Statins reduce the risk of AD by reducing the cholesterol levels by interfering with the activity of enzyme. Moderate take of alcohol and intake of N-3 fatty acids reduces the risk of AD. Studies have shown that intake of N-3 fatty acids and weekly consumption of fish can decrease the risk of AD by 60 %.

Pharmacological treatments of Alzheimer’s disease are limited. Recent observational studies have shown that use of non-steroidal anti-inflammatory drugs (NSAIDs) may protect against the development of the disease, possibly through their anti-inflammatory properties.(Mahyar et al 2007)

The results from research which has been carried out has been varied. Caffeine can be used as a treatment in Alzheimer’s disease (Chuanhai et al 2009). Caffeine causes most of its biological effects via antagonizing all types of adenosine receptors (ARs), as does adenosine, exerts effects on neurons and glial cells of all brain areas. In consequence, caffeine, when acting as an AR antagonist, is doing the opposite of activation of adenosine receptors due to removal of endogenous adenosinergic tonus. Caffeine, through antagonism of ARs, affects brain functions such as sleep, cognition, learning, and memory, and modifies brain dysfunctions and diseases i.e. Alzheimer’s disease. (Gary W et al 2009).

Studies shows that people that take regular supplements decrease the risk of AD. Many people take folate (vitamin B9), vitamin B12, and vitamin E. However, there is no strong evidence that taking these vitamins prevents AD or slows the disease once it occurs. Recent studies have shown that people believe that the herb ginkgo biloba prevents or slows the development of dementia. However, high-quality studies have failed to show that this herb lowers the chance of developing dementia. Treatment of ancillary symptoms of Alzheimer disease has improved as well. Techniques have evolved to treat depression, sleeplessness, agitation, paranoia. Also family support is a cure in its own why which gives the patient a feel good feeling to overcome AD.

References

Volume 20, Supplement 1, 2010 – “Therapeutic Opportunities for Caffeine in Alzheimer’s Disease and Other Neurodegenerative Diseases” (Guest Editors: Alexandre de Mendonca and Rodrigo A. Cunha) Pages 3-15

Volume 20, Number 3, June 2010 – Special Issue “Basics of Alzheimer’s Disease Prevention” (Editor: Jack de la Torre) Pages 687-688

Supplement 3, November 2010 – “Anesthetics and Alzheimer’s Disease” (Guest Editors: Pravat K. Mandal and Vincenzo Fodale) – November 2010 Pages 1-3

Recommendations for the diagnosis and management of Alzheimer’s disease and other disorders associated with dementia: EFNS guideline

Volume 14, Issue 1, pages 1–26, January 2007, From mild cognitive impairment to prodromal Alzheimer disease: A nosological evolution J.L. Molinuevo, C. Valls-Pedret, L. Rami, Volume 1, Issue 3, June 2010, Pages 146-154

G. Waldemar; B. Dubois; M. Emre; J. Georges; I. G. McKeith ; M. Rossor; P. Scheltens; P. Tariska; B. Winblad, Article first published online: 9 JAN 2007, European Journal of Neurology

Mahyar Etminan et al 2003,Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer’s disease: systematic review and meta-analysis of observational studies doi: 10.1136/bmj.327.7407.128, BMJ. 2003 July 19; 327(7407): 128.

Gary W Arendash, Takashi Mori, Chuanhai Cao, Malgorzata Mamcarz, Melissa Runfeldt, Alexander Dickson, Kavon Rezai-Zadeh, Jun Tan, Bruce A Citron, Xiaoyang Lin, Valentina Echeverria, and Huntington Potter. Caffeine Reverses Cognitive Impairment and Decreases Brain Amyloid-%u03B2 Levels in Aged Alzheimer’s Disease Mice. Journal of Alzheimer’s Disease, Volume 17:3 (July 2009)

Chuanhai Cao, John R Cirrito, Xiaoyang Lin, Lilly Wang, Deborah K Verges, Alexander Dickson, Malgorzata Mamcarz, Chi Zhang, Takashi Mori, Gary W Arendash, David M Holzman, and Huntington Potter. Caffeine Suppresses Amyloid-%u03B2 Levels in Plasma and Brain of Alzheimer’s Disease Transgenic Mice. Journal of Alzheimer’s Disease, Volume 17:3 (July 2009)

John B. Standridge MD (2004) Pharmacotherapeutic approaches to the prevention of Alzheimer’s disease, Department of Family Medicine, University of Tennessee Health Science Center College of Medicine, Chattanooga Unit, Chattanooga, Tennessee, USA.

Zandi PP et al (2002 Nov 6), Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study, JAMA. 288(17):2123-9.

Postiglione A, Napoli C, (1995 Aug 6), Curr Opin Lipidol. Hyperlipidaemia and atherosclerotic cerebrovascular disease. (4):236-42

http://www.alz.org/national/documents/topicsheet_treatments.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC165707/?tool=pubmed

http://www.webmd.com/alzheimers/guide/treatment-overview

http://www.ant.org.tw/Mag_Files/19-4/B.19-4ra.pdf

http://www.ncbi.nlm.nih.gov/pubmed/21213151

http://www.alz.org/downloads/Facts_Figures_2011.pdf

http://www.cliffsnotes.com/study_guide/Transmission-of-Nerve-Impulses.topicArticleId-22032,articleId-21935.html

http://www.psychatlanta.com/documents/namenda.pdf

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Zinc finger nuclease technology and its potential for modelling and treating disease

Introduction

Methods to introduce site specific, stable modifications in complex genomes hold great potential, not only for the study of gene function but also for biotechnological and therapeutic applications (Sollu et al., 2010). A promising new approach is based on zinc-finger nucleases (ZFNs), artificially constructed endonucleases that are designed to make a double strand break in a pre-determined genomic target sequence. This can then be followed by the generation of desired modifications during subsequent DNA repair.

ZFNs are engineered to contain a DNA binding domain, composed of zinc finger proteins, and a non-specific endonuclease domain derived from the FokI restriction enzyme (Urnov et al., 2010). The zinc finger protein region provides a ZFN with the ability to bind to a discrete base sequence. Each zinc finger domain consists of ? 30 amino acids which fold into a ??? structure, this is stabilised by chelation of a zinc ion by the conserved Cys2-His2 residues (Durai et al., 2005). Each domain recognises and binds to approximately 3bp of DNA. Binding to longer sequences is achieved by linking several of these zinc fingers in tandem to form zinc finger proteins. As the catalytic FokI domain must dimerise to induce a double strand break (Vanamee et al., 2001), two different ZFN subunits are designed that bind the sequence of interest in the opposite orientation and with the correct spacing. The combined target sequence is sufficient in length to be statistically unique, even in complex genomes (Sollu et al., 2010) (figure 1).

ZFNs have been proven to work successfully in Arabidopsis thaliana (Zhang et al., 2010), Caenorhabditis elegans, Drosophila melanogaster (Carroll et al., 2008), zebrafish (Doyon et al., 2008), rats (Mashimo et al., 2010) and human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) (Zou et al., 2009).

Mechanisms of DNA double strand break repair

All eukaryotic cells have effective mechanisms to repair double strand breaks in DNA. The two primary repair pathways are non-homologous end joining (NHEJ) and homologous directed repair (HDR) (Jackson and Bartek, 2009). These highly conserved pathways can be exploited to generate a defined genetic outcome across a wide range of cell types (Urnov et al., 2010).

In NHEJ, the two broken ends are simply ligated back together. If the double strand break is complex, creating ends that are not compatible then repair by NHEJ will be mutagenic; the repaired DNA will contain small insertions or deletions at the site of the break, resulting in gene inactivation (Durai et al., 2005). If a double stranded oligonucleotide is provided with overhangs (sticky ends) complementary to those left by the ZFNs, it will be ligated into the chromosome, this approach can be used to add tags to endogenous genes. Alternately, two simultaneous double strand breaks made on the same chromosome can lead to a deletion of the entire intervening stretch (Lee et al., 2010) (figure 2).

The other major repair pathway is HDR, a form of homologous recombination that faithfully copies the genetic information from a DNA molecule of related sequence. In HDR the 5? ends of the double strand break are resected to generate 3? single stranded tails, allowing strand invasion by donor DNA, which serves as a template for DNA replication (Durai et al., 2005). In normal double strand break repairs the DNA donor is the sister-chromatid, therefore the template is identical to the damaged DNA, resulting in a perfect form of repair. In gene targeting an exogenous donor DNA template is provided (usually an episomal or linear extrachromosomal donor) in combination to the ZFNs. If the donor DNA specifies solely a single nucleotide change, such as a restriction fragment length polymorphism (RFLP) encoding a novel allele, this will result in gene correction, that subtly edits the endogenous allele (Urnov et al., 2005). HDR can also be used for the addition of genes, if the donor provided carries an open reading frame (ORF), a transgene or even multiple trasngenes at the position corresponding to the site of the break, the sequence will be transferred to the chromosome (Moehle et al., 2007) (figure 2).

Figure 2 | Types of genome editing made possible using ZFNs. The two primary repair pathways: non-homologous end joining (NHEJ) and homologous directed repair (HDR) with the different outcomes that can result from the introduction of a site specific DNA double strand break. Adapted from (Urnov et al., 2010).

Gene edition using ZFNs – gene disruption and gene correction

The simplest means of gene editing is gene disruption, which takes advantage of errors introduced during DNA repair to disrupt or abolish the function of a gene or genomic region. Gene knockout (KO) is an affective tool for analysing gene function and generating model animals that recapitulate genetic disorders. Using ZFN technology, Mashimo et al., 2010 created knockout rats with X-linked Server Combined Immunodeficiency (X-SCID). They injected mRNAs encoding ZFNs designed to target the rat interleukin 2 receptor gamma (II2rg) locus, where orthologous human and mouse mutations cause X-SCID, into the pronucleus of fertilised rat oocytes. They found that the offspring carried a variety of deletion/insertion mutations, most of which were expressed as frameshift or splicing errors, resulting in no or very little expression of II2rg mRNA. The ZFN modified founders faithfully transmitted their genetic changes to the next generation along with the SCID phenotype (Mashimo et al., 2010). The X-SCID rats generated in studies such as this can be valuable in vivo tools for pre-clinical testing during drug development or gene therapy as well as model systems for examining the treatment of xenotransplanted malignancies.

Another approach, gene correction allows the transfer of single nucleotide changes from a DNA donor to the chromosome following a ZFN induced double strand break. Urnov et al., 2005 designed ZFNs directed against the X-linked SCID mutation hotspot in the interleukin-2 receptor-? (IL2R?) gene. Using the ZFNs on K562 cell lines, they found that ~20% of the population carried a modification at the endogenous loci and about 7% of the cells were homozygous for the donor specified genotype, which was accurately reflected at the mRNA and protein levels. The modified cells were found to be stable for extended periods in cell culture while transcriptionally and translationally manifesting their new genotype (Urnov et al., 2005).

Gene addition

Transgenesis of human cells is used in functional genomics, proteomics and protein structure-function studies, and is routinely accomplished by random integration combined with drug selection. Expression of a randomly integrated transgene can be unpredictable and tends to be unstable over time due to epigenetic effects (DeKelver et al., 2010). The precisely placed double strand break induced by ZFNs can stimulate integration of long DNA stretches into a predetermined genomic location, resulting in site-specific gene addition. Moehle et al., 2007 introduced ZFNs directed against the interleukin-2 receptor-? (IL2R?) gene (exon 5), in combination with a DNA donor carrying a 12bp tag and a 900bp open reading frame (ORF), flanked by locus specific homology arms into HEK293 cells. After 72 hours, ~5% of the chromatids had acquired the transgene between the ZFN recognition sites (Moehle et al., 2007).

ZFNs have also been used in human EPCs and iPSC to efficiently target a drug resistance marker to a specific gene. Hockemeyer et al., 2009, used ZFNs specific for the OCT4 (POU5F1) locus and a donor constructs containing a splice acceptor (SA) followed by an enhanced green fluorescent protein (eGFP)-2A-puromycin cassette. They reported expression of two proteins, a fusion protein comprising the first 132 amino acids of human OCT4 fused to eGFP (OCT4EX1-eGFP) and puromycin N-acetyltransferase, both under the control of the endogenous OCT4 promoter, therefore generating reporter cells which can monitor the pluripotent state of human ESCs (Hockemeyer et al., 2009).

Therapeutic applications of ZFNs

Site specific manipulation of the genome by ZFNs has revolutionised biology and holds great promise for molecular medicine (Lombardo et al., 2007). For example a corrected allele of a disease causing gene could be curative in several monogenetic diseases. Alternatively, the knockout of a gene encoding a virus receptor could be shown to eliminate rather than merely reduce infection.

ZFN mediated gene disruption is the first ZFN based approach that has been taken to clinical trails, specifically for the treatment of glioblastoma (NCT01082926) and HIV (NCT00842634 and NCT01044654). In glioblastoma phase I clinical trials, the glucocorticoid receptor gene is disrupted by ZFNs as part of a T cell based cancer immunotherapy (Urnov et al., 2010). In the HIV trials, ZFNs targeting the chemokine (C-C motif) receptor type 5 (CCR5) gene have been delivered via adenoviral vector to isolated T cells from subjects. The CCR5 protein is required for certain common types of HIV infection to enter into and infect T cells. The ZFN mediated CCR5 knockout T cells then are returned to the subject. (Perez et al., 2008). An advantage of using ZFN technology is that it creates a fully penetrant, heritable gene knockout that will persist for the lifetime of that cell and its progeny, therefore removing the need for persistent therapeutic exposure.

Limitations of ZFNs

A potential limitation of the ZFN targeting approach is off-target DNA breaks induced at related sequences elsewhere in the genome, which may cause unpredictable genotoxic. To overcome this, ZFNs can be designed to with longer DNA recognition sites such as 12bp-18bp, which upon dimerisation of the FokI nuclease domain will recognise a 24bp-23bp sequence (such sites are rare even in complex genomes). This alongside bioinformatic tools such as SELEX (systematic evolution of ligands by exponential enrichment) can be used determine the specificity for a ZFN DNA binding domain and generate a rank order of potential off-target site with highest similarity (Tuerk et al., 1990). Another challenge when designing ZFNs is the choice delivery system (DNA, RNA or viral), the ideal method has proven to be dependent on cell type. Lombardo et al., 2007 found that integrase-defective lentiviral vectors (IDLV) support functional delivery of both ZFNs and donor DNA templates to a variety of cell types, including haematopoietic progenitors and embryonic stem cells (Lombardo et al., 2007).

Aside from the various limitations, ZFN technology has allowed site specific genome editing to become established in human cells and a number of model organisms, opening the door to a powerful range of new experimental and therapeutic possibilities.

References

Carroll, D., Beumer, K. J., Morton, J. J., Bozas, A. and Trautman, J. K. (2008) ‘Gene targeting in Drosophila and Caenorhabditis elegans with zinc-finger nucleases’, Methods Mol Biol, 435, pp. 63-77.

DeKelver, R. C., Choi, V. M., Moehle, E. A., Paschon, D. E., Hockemeyer, D., Meijsing, S. H., Sancak, Y., Cui, X., Steine, E. J., Miller, J. C., Tam, P., Bartsevich, V. V., Meng, X., Rupniewski, I., Gopalan, S. M., Sun, H. C., Pitz, K. J., Rock, J. M., Zhang, L., Davis, G. D., Rebar, E. J., Cheeseman, I. M., Yamamoto, K. R., Sabatini, D. M., Jaenisch, R., Gregory, P. D. and Urnov, F. D. (2010) ‘Functional genomics, proteomics, and regulatory DNA analysis in isogenic settings using zinc finger nuclease-driven transgenesis into a safe harbor locus in the human genome’, Genome Res, 20, (8), pp. 1133-42.

Doyon, Y., McCammon, J. M., Miller, J. C., Faraji, F., Ngo, C., Katibah, G. E., Amora, R., Hocking, T. D., Zhang, L., Rebar, E. J., Gregory, P. D., Urnov, F. D. and Amacher, S. L. (2008) ‘Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases’, Nat Biotechnol, 26, (6), pp. 702-8.

Durai, S., Mani, M., Kandavelou, K., Wu, J., Porteus, M. H. and Chandrasegaran, S. (2005) ‘Zinc finger nucleases: custom-designed molecular scissors for genome engineering of plant and mammalian cells’, Nucleic Acids Res, 33, (18), pp. 5978-90.

Hockemeyer, D., Soldner, F., Beard, C., Gao, Q., Mitalipova, M., DeKelver, R. C., Katibah, G. E., Amora, R., Boydston, E. A., Zeitler, B., Meng, X., Miller, J. C., Zhang, L., Rebar, E. J., Gregory, P. D., Urnov, F. D. and Jaenisch, R. (2009) ‘Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases’, Nat Biotechnol, 27, (9), pp. 851-7.

Jackson, S. P. and Bartek, J. (2009) ‘The DNA-damage response in human biology and disease’, Nature, 461, (7267), pp. 1071-8.

Lee, H. J., Kim, E. and Kim, J. S. (2010) ‘Targeted chromosomal deletions in human cells using zinc finger nucleases’, Genome Res, 20, (1), pp. 81-9.

Lombardo, A., Genovese, P., Beausejour, C. M., Colleoni, S., Lee, Y. L., Kim, K. A., Ando, D., Urnov, F. D., Galli, C., Gregory, P. D., Holmes, M. C. and Naldini, L. (2007) ‘Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery’, Nat Biotechnol, 25, (11), pp. 1298-306.

Mashimo, T., Takizawa, A., Voigt, B., Yoshimi, K., Hiai, H., Kuramoto, T. and Serikawa, T. (2010) ‘Generation of knockout rats with X-linked severe combined immunodeficiency (X-SCID) using zinc-finger nucleases’, PLoS One, 5, (1), pp. e8870.

Moehle, E. A., Rock, J. M., Lee, Y. L., Jouvenot, Y., DeKelver, R. C., Gregory, P. D., Urnov, F. D. and Holmes, M. C. (2007) ‘Targeted gene addition into a specified location in the human genome using designed zinc finger nucleases’, Proc Natl Acad Sci U S A, 104, (9), pp. 3055-60.

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Free Essays

Norovirus and gastrointestinal disease

Introduction

Norovirus is currently recognized as the most important non-bacterial pathogen causing gastroenteritis. It is believed that majority of gastroenteritis that occur throughout the globe is attributed to Norovirus. Norovirus was first recognised through immunoelectron microscopy (IEM) in 1972. However, it is only over the past decade that Norovirus has been of great interest to the basic scientists, virologists, epidemiologists and public health experts. There is no doubt that outbreaks or epidemics of Norovirus in the coming years will challenge the medical community to the limit. Globalisation has created a single, very mobile mega-population of people on earth in which more viruses can thrive, and, a highly infectious illness caused by Norovirus can spread rapidly, thus creating epidemics or even pandemics. The potential breakthrough in the development of Norovirus vaccine with the development of effective antigenic viral-like particles (VLP), and the recognition that Norovirus evolves with antigenic drift will pose exciting challenges to all stakeholders. The other challenges or obstacles which we face include understanding the pathogenesis of the Norovirus in the gastrointestinal tract and identifying the site in the gastrointestinal tract which the virus replicates. This knowledge will hopefully allow the development of targeted antiviral therapy and thus prevent manifestation of severe clinical symptoms.

This is a review of this very exciting, virus and I have chosen to amalgamate the current literatures into the following topics:

Virology- Classification and structure
Biology- Replication and infectivity
Epidemiology- Geographic and temporal distribution
Transmission
Clinical features
Pathogenesis
Immunity
Prevention and control
Recent knowledge on contamination/sanitation and personal hygiene
Vaccine development
Treatments- Current and future
Health impact of Norovirus outbreaks in the coming era

Virology

Classification

Although Norovirus was first viewed in 1972, it was not until 1990 when it was classified. Classification of Norovirus could finally be performed due to the successful cloning of the viral genome (1). Molecular cloning and characterisation of Norovirus genome allowed this virus to be classified as a member of Caliciviridae family and it is known as a Group B Biodefense Pathogen. Caliciviruses are small (27-40nm), non-enveloped, icosahedral particles with single-stranded RNA of positive polarity. The name calicivirus comes from the Latin word calyx, meaning “cup” or “goblet”, which describes the cup-shaped depression, as observed under electron microscopy. Although they share similar features to that of the picornaviruses, caliciviruses are distinguished from their counterpart by having a larger genome and having distinctive spikes on the surface. Another example of calicivirus is the Hepatitis E virus (2). Currently, there are a few serotypes of Norovirus which were successfully identified through immunoelectron microscopy (IEM) and enzyme-linked immunosorbent essay (ELISA), which are represented by Norwalk virus (NV), Hawaii virus (HV), Snow Mountain agent (SMA), Desert Shield virus (DSV) and Southampton virus. (1).

Currently, there are five main genogroups of Norovirus being identified (GI, GII, GIII, GIV and GV). Noroviruses, which can be found in humans, are from three genogroups (GI, GII and GIV). However, those that are commonly isolated in cases of acute gastroenteritis in humans belong only to two genogroups (GI and GII), which can then be further divided into genetic cluster or genotypes (i.e GI.1, GII.15, GIV.2 etc). There are now, at least 25 genotypes of Norovirus which were successfully identified, with the prototype Norwalk virus being labelled as GI.1 (Genogroup I, genotype 1) (3) and present within this genotype are numerous subtypes. The presence of this diversity of Norovirus strains are mainly due to both the accumulation of point mutations associated with error-prone RNA replication and to recombination between two related viruses (4, 5). Genogroup I (GI) includes76 Norwalk virus, Desert Shield virus and Southampton virus and Genogroup II (GII), includes Bristol virus, Lordsdale virus, Toronto virus, Mexico virus, Hawaii virus and Snow Mountain virus. Norwalk virus (NV), Snow Mountain virus (SMV), and Hawaii virus (HV) are the prototype strains of genotypes GI.1, GII.2, and GII.1 and are the causative agents of an estimated 5%, 8%, and 7% of Norovirus outbreaks, respectively (6). Genogroups III and V (GIII and GV) have only been identified in animals.

Structure

Through structural studies and visualisation of Norovirus by electron microscopy, it is now proven that the Norovirus is composed of 90 dimers of the major capsid protein VP1 and one or two copies of the minor structural protein VP2 (7) which recognizes the histo-blood group antigens, which are regarded as receptors and host-susceptibility factors for infection (3).

Figure 1. Structure of Norwalk Virus and Genome

Non-enveloped, T=3 icosahedral symmetry, about 23-40 nm in diameter. Each virus particle is composed of 180 molecules of VP1 proteins which form 90-arch-like capsomers at all the local and strict twofold axes surrounding the hollows. The proteins in the capsid then folds into two main domains which are, the shell (S) domain and the protruding (P) domain, which contains two further subdomains, P1 and P2. The protruding, P domain functions to increase the stability of the capsid by increasing the intermolecular contacts between the dimeric subunits, thus, leading to speculation that it may control the size of the capsid. However, the S domain contains all the necessary protein requirements to initiate the assembly of the capsid (8).

Norovirus has single stranded RNA genome and is predicted to contain three open reading frames (ORF) (9). The Norovirus genome is linear and contains approximately 7600 nucleotides (nt) (Southampton virus-7708nt, Lordsdale virus- 7555nt) (10). The ORF1 (a polyprotein that contains sequence of amino acid which shows much similarity to that of Picornaviruses) is predicted to encode the capsid protein. ORF1 may be cleaved by 3CL proteases into 6 proteins (11). ORF2 and ORF3 are not shown in the diagram. However, until now, it is not known whether these ORF would be translated or what the function of its translated protein would be.

In a recent study, Norovirus- like particles was viewed under atomic force microscopy. Scientist exposed the Norovirus-like particles in environments with PH ranging from 2 to 10. This range of pH values represents the pH of the natural environment in which Norovirus thrives. The study revealed that the Norovirus-like particles were resistant to indentation of measure of <300 bar at acidic and neutral pH. However, when the Norovirus-like particles were subjected to same indentation at a pH of 10, the capsid failed to regenerate and was irreversibly destroyed (12). All these studies which are still at an early stage will pave the way for further understanding of Norovirus.

Biology

Norovirus Replication Strategy

Progress on understanding the basic mechanisms of virus replication has been far slower due to the inability to cultivate virus in the laboratory. Therefore, the replication strategy of this virus remains speculative and is presumed that its replication cycle is of a similar manner to that of picornaviruses (2). As in the picornaviruses, the viral particle will bind to the cell surface receptors. This will result in a conformational change in the viral capsid proteins, and thus, releasing myristic acid (a common saturated fatty acid). This acid then helps in forming a pore in the cell membrane of the host cell and through this tiny hole; the RNA of the virus is injected (101). Once inside the cell, the RNA unwinds and the positive strand RNA genome is replicated through a double-stranded RNA intermediate which is formed using viral RDRP (RNA-Dependent RNA polymerase). Translation by host cell ribosomes is not initiated by the usual 5? G cap; instead it is initiated by IRES (Internal Ribosome Entry Site). The viral replication cycle is short and it takes approximately 8 hours to complete one cycle of replication. Within 30 minutes after initial infection, cell protein synthesis – essentially the macromolecular synthesis of cell is “shut off”. Over the next one to two hours there is a loss of margination of chromatin and homogeneity in the nucleus. This is followed by synthesis of the viral proteins. Subsequently, a vacuole appears in the cytoplasm close to the nucleus and this vacuole gradually starts to coalace covering the whole cell. After 3 hour time, the cell plasma membrane becomes permeable and at 4–6 hours the virus particles assemble, and occasionally could be seen in the cytoplasm. At about 8 hours, the dead cell lyses and releases the viral particles (101).

Infectivity of Norovirus

Studies of the stability and hardiness of Norovirus have been done by experimental infection on humans. As Norovirus is the most important cause of food and waterborne disease, it is not unexpected that it is resistant to inactivation by treatment with chlorine concentrations which is usually used in drinking water (1). Norovirus can retain its infectivity even after:- i) exposure to pH2.7 for 3 hours at room temperature, ii) treatment with 20% ether at 4°C for 24 hours, or iii) incubation at 60°C for 30 min (13). Norovirus can also retain infectivity after freezing (14).

Recent reports have shown that through current sensitive antigen detection methods, Norovirus excretion was detected in >90% of ill volunteers. Viral shedding peaks 1-3 days after onset of symptoms, and studies have shown that the viral antigen may be shed for up to 56 days. Shedding of virus can occur in asymptomatic individuals and it can be prolonged in immunocompromised people. Also, antigen shedding can precede illness (15hr after infection and before symptomatic illness) (15).

Epidemiology

The successful cloning and expression of the Norovirus genome has led to the development of new assays which has allowed various epidemiological studies to be performed. Recent epidemiological studies have indicated that the infection with Norovirus is much more widespread than previously recognised (16).

Geographic and Temporal Distribution

Norovirus is highly infectious and can be spread easily from one person to another and is the leading cause of epidemic gastroenteritis in both the developed and developing countries. However, this epidemic gastroenteritis is usually mild, thus, differentiating it from infantile gastroenteritis (which is mainly caused by Rotavirus), which is a much more severe, and often life threatening diarrheal illness in infants and young children. Incidence of infection by Norovirus has been detected in all continents, and therefore, it has a global distribution. It has been quoted that in the United States, more than 90% of the outbreaks of gastroenteritis in the community, for which the cause was previously unknown, can now be attributed to Norovirus (2). Infection by Norovirus do occur all year round, however, its incidence is markedly increased during cold weather months (17). Outbreaks typically occur in group settings such as cruise ships, schools, camps hospitals and nursing home where people gather in confined areas (2) and target a number of high risk populations, particularly young children and the elderly, travellers, soldiers and immunocompromised patients or those who are recipient of organ transplant. Every year, up to 1 million people in the UK are thought to be infected by Norovirus (18). If the Norovirus is brought into the hospital environment by someone incubating the infection, then it can easily spread to vulnerable hospital patients and also to staff. It is known to cause large outbreaks of infection in hospital which results in a lot of patients and staff being affected leading to closure of wards in order to prevent further spread. This has posed a huge problem on care provision. Hospitals, therefore, have very strict policies in place to control the spread of Norovirus which will be discussed later.

Transmission

Humans are believed to be the only host of the human Norovirus. Norovirus is transmitted mainly by the fecal-oral route. However, it can also be transmitted through infected vomitus (3) and there is currently increasing evidence that it can be transmitted through airbourne or fomite transmission (19 & 20). The infection of Norovirus is enhanced by several features which facilitate their spread. First, it has a low infection dose (approximately 18 to 1000 viral particles) (21) which allow the virus to spread through droplets, person-to-person contact and through environmental contamination. Secondly, excretion of virus in stools continued for several weeks even after recovery, thus, increases the risk of secondary spread which is a particular concern among food handlers and family members (22). Thirdly, the virus is resistant to a wide range of temperatures, chemicals and pH. The virus is able to persist on environmental surfaces and contaminated objects eg in swimming pools, contaminated drinking water, ice, bakery products and also in raw oysters, fruits and vegetables which are eaten uncooked and cold foods (celery, melon, vermicelli, sandwiches and cold cooked ham) (3). Fourthly, due to the fact that there is a great diversity of Norovirus strains and the lack of long term immunity, it can result in occurrence of repeated infection throughout life. Finally, the Norovirus genome can also undergo mutations, which causes antigenic shift and recombination, which result in evolution of new strains of Norovirus which are capable of infecting hosts. Asymptomatic infections do occur, and such person may be the carriers of some outbreaks. In recent time, there is an increased in outbreaks in military camps and with the elderly who are staying in nursing or shelter homes, and also in hospital settings (19 & 20). These infections can be catastrophic because of high secondary attack rates, and such outbreaks can last for several months (18).

Clinical features

An unresolved problem related to transmission of Norovirus is how long an affected individual can stay infectious. Firstly, the incubation period of the virus is 10-51 hours. The main symptoms are sudden onset of vomiting (more common in children) and abdominal cramps (in 37-45% of the cases) followed by watery diarrhoea (more common in adults). The stools usually do not contain any blood or mucus and asymptomatic infection do occur in approximately 1/3 of the population. The duration of symptomatic illness lasts between 1-3 days (28-60 hr) but can last longer (4-6 days) in nosocomial outbreaks (3) and among children younger than 11 years of age (22). In 15% of patients, it lasts longer than 3 days. The illness also lasts longer in immunocompromised patients and in people with chronic illnesses (3). In immunocompetent adults, the course of Norovirus infection is rapid, with an incubation period of 24–48 hours and resolution of symptoms within 12–72 hours (23). The infection is usually less severe compared to other diarrheal infection. However, it can lead to dehydration and requires hospitalization, especially among children with an age of <5 yrs and adults, >65 yrs. Fatalities have been reported in relation to outbreaks of gastroenteritis among the elderly in nursing homes (24) and in the United Kingdom, there is an estimate of about 80 deaths from Norovirus every year among people who are older than 64 years of age (25). However, there are usually no long term effects of Norovirus infection and majority of patients recovers fully.

Pathogenesis

Because of the failure to cultivate the Norovirus in laboratory properly, our knowledge regarding the pathogenesis of Norovirus come mainly from physical, histological and biochemical studies on infected volunteers who took part in surveys. Proximal intestinal biopsy specimens were taken from ill volunteers and histological changes were compared to healthy individuals. Ill volunteers showed broadening and blunting of intestinal villi, crypt cell hyperplasia, cytoplasmic vacuolization and infiltration of polymorphonuclear and mononuclear cells into the lamina propria but the mucosa itself remaining intact. No histological changes were seen in the gastric fundus or in antrum or colonic mucosa (26). The extent of small intestine involvement remains unknown because studies have only examined the proximal small intestine, and the site of replication of the virus has yet to be identified. Studies have shown that small intestinal brush border enzymatic activity (alkaline phosphatase, sucrase and trehalase) were reduced, resulting to steatorrhea (lipids in stools) and transient carbohydrate malabsorption (27). Jejunal adenylate cyclase activity was not elevated (28) and changes in gastric secretion of hydrochloric acid (HCL), pepsin and intrinsic factor have been linked to these histological changes. In addition, gastric emptying was delayed and the reduced gastric motility may result in nausea and vomiting associated with this gastroenteritis.

The binding specificity of Norovirus is based on the histo-blood group antigens. These histo-blood group antigens are complex carbohydrates (oligosaccharides) linked to proteins or lipids and are located on the mucosal epithelial of the digestive tracts and are present as free oligosaccharides in saliva and milk (29). The three major families of histo-blood group antigens- ABO, Lewis and secretor families- are involved in the binding of Norovirus (29). Different Norovirus genotypes have different affinity for ABO antigens. For example, GI Norovirus has a higher affinity for blood group antigens A and O whereas GII Norovirus has a higher affinity for blood group antigens A and B (30). The P2 domain on the viral capsid plays a key role in the binding of these Norovirus to the histo-blood group antigens (31).

Prevention and control

Outbreaks of Norovirus can result in loss of income and significant morbidity because of frequent secondary transmission of the disease. Places which are more prone to Norovirus outbreaks and are of particular concern are normally places with a closed environment such as hospitals, nursing homes, ships and planes. Because Norovirus is highly infectious and spreads easily, and can be spread via asymptomatic individuals, the prevention of Norovirus outbreaks has become a major obstacle and poses a challenge for us. Norovirus can begin with a single common source of contaminated food (i.e. raw oysters, fruits and vegetables) and can rapidly spread like wildfire through person-to-person contact. Stopping an outbreak of Norovirus requires herculean efforts to sterilise and clean the environment (eg. on cruise ships, camp sites, nursing home, hospital wards or disaster sites), and even then, the epidemics will only subside once the viral pool have been totally eradicated (32,33).

No specific methods are available for complete prevention of Norovirus infection or illness due the agent being extremely contagious. Therefore, control efforts are targeted and focused on identifying the source and the subsequent removal of that source (eg, an infected food handler, contaminated water supply or even contaminated food supply, which is often the case with fruits and shellfish- in particular, oysters) which will then reduce the chance of the virus spreading (34). It is advised that ill food handlers should not be able to retain to their job and that strict personal hygiene be enforced among food handlers as they are one of the main causes of outbreaks. However, even under these strict regulations, both measures have shown limited success. The key to stopping the continuous spread of outbreaks is by preventing the secondary spread of the virus which spread through person-to person contact and from contaminated environmental surfaces which normally occur in cruise ships and other institutions. The fact that asymptomatic infection can occur and that the antigen can still be shed 2-3 weeks after exposure need to be kept in mind to facilitate the managing of outbreaks. Methods to manage the outbreak of Norovirus infection will probably improve in the near future as new tests are being carried out in epidemiological research of virus transmission.

Recent knowledge on contamination, sanitation and personal hygiene

In an outbreak, whether in a hospital or other environment, various methods can be enforced to reduce the spread of Norovirus infection. It is also important to note that Norovirus gastroenteritis, which is highly contagious tend to spread in crowded areas and may be difficult to control, therefore, below, are just a few techniques which can help in controlling this spread.

Proper hand washing techniques and washing hands with soap and water is the key to preventing Norovirus from spreading. Note that, alcohol hand gel does not kill the virus entirely, but it may still be useful in areas where water is inaccessible. Also, the efficacy of the alcohol based sanitizers depends on the alcohol type and concentrations as well as the amount of viral particles present (35).

* Medical staff and aid workers should clean their hands prior to and after touching any patient but it is particularly important that staffs wash their hands with soap and water after attending to a Norovirus patient to prevent the infection from spreading from one patient to another patient via their hands. Staffs should also be educated about the importance of personal hygiene and about the importance of washing hands.

* Visiting relatives of patients in hospitals should also wash their hands with soap and water after visiting a ward which has Norovirus and they should not interact with other patients other than the person they have come to visit.

* Staff and visitors should wash their hands before handling food and after visiting the toilet. Hand washing facilities should also be provided especially in high risk areas which are prone to Norovirus infection, such as bathrooms, eating areas, diaper-changing areas and even day care centres.

* Proper hand washing techniques (eg. Rub palm to palm with fingers interlaced and rub back of each hand with palm of the other hand with fingers interlaced) should also be advised and encouraged.

* Strict personal hygiene among food handlers and aid workers should be enforced to prevent outbreaks of Norovirus.

2. Isolating patients with the virus.

*Patients with Norovirus must immediately be isolated from non-infected patient until their symptoms subside. The infected patient should be placed in a single room, but if there are a few cases of infection on the ward, infected patients should then be nursed in a dedicated bay. If there are a large number of cases, the ward should be close to new admissions. Visiting should also be restricted to prevent visitors getting the infection and thus, preventing the subsequent secondary infection of the disease.

3. Cleaning.

*Enhanced cleaning using bleach-containing products are needed to eradicate Norovirus from the environment. Vomit and diarrhoea must be cleaned up immediately and general ward cleaning must be increased. Alcohol based surface disinfectants are usually insufficient. Waste should also be dumped properly in the allocated bins.

*Aggressive environmental sanitization by cleaning with proper surface disinfectants and sterilisation of bathroom surfaces, bedding and lines are also essential to decrease secondary spread (32).

* Studies have shown that when bleaching agent is used on feline caliciviruses, it can inactivate the activity of the virus. Also, the effect of the bleaching agent is superior compared to that of ammonium compounds or phenols (36).

4. Symptomatic people must stay away from hospital.

*Staff and visitors who develop symptoms must not come into the hospital and they must remain away from the hospital until they have been free of symptoms for 48-72 hours. Staff must be cleared by occupational health before returning to work.

Immunity and Vaccine Developed

To develop future vaccines for the prevention of Norovirus infection, the nature of the immunity to Norovirus is of particular importance. In an early study of immunity of the human response system to Norovirus illness, some volunteers who became ill after being exposed to the virus had partial immunity to the disease upon exposure 6 to 14 weeks later, but lost the immunity 27 to 42 months later (37). However, recent studies have shown that these early finding may be inaccurate, since the dose required to infect 50% of volunteers is as low as 18 infectious particles, whereas the dose used in the early study was more than 105 time higher (21). Immunity developed from exposure to a lower dose of Norovirus might be greater and more cross-reactive than immunity against a much higher dose. Therefore, studies on this possibility are still on going.

The high incidence of illness caused by Norovirus infections especially among both the young and the elderly have led to some investigations to consider the potential role of vaccines in helping to regulate this infection. The vaccine should be designated towards specific target groups, such as infants (as part of their routine schedule for childhood immunization), the elderly, food handlers, military personnel, travellers, health care workers and nurses in day-care centres (3). The development of vaccines could also play a role in helping to reduce the number of childhood mortality and controlling diarrheal disease in infants. In a recent study, it is noted that 15% of hospitalization of children for diarrhoea in India and 31% in Peru were associated with Norovirus infection (38) and these percentages may be contributing greatly towards the estimated 1.6 million children who die each year from diarrhoea. Nevertheless, recent breakthrough in research has successfully produced Norovirus-like particles (NVLP). These particles have almost identical characteristics to the original Norovirus as it has resistant properties towards acidic pH and is also heat-stable. When these particles are given orally or intranasally to human, it can produce an antigenic effect, stimulating the production of anti-Norovirus antibodies (B and T cell responses) within the human body (39). Therefore, these particles are now being studied, hoping that it could be used as a platform and lead us to discovering a cure one day.

However, there are many obstacles towards the development of a vaccine for Norovirus. Firstly, there is certainly a lack of understanding of the physiology of the virus due to the failure to cultivate them in laboratories. Thirdly, there is limited understanding on why individuals cannot develop long term immunity towards the virus. Furthermore, the virus can also withstand a wide range of temperatures and pH thus increasing their survivability. Also, the virus has multiple routes of transmission, and finally, the Norovirus strain is rapidly evolving and mutating, thus, posing a major challenge for us in developing a vaccine, which is much similar to the situation to that of the influenza viruses. Similar to that of the influenza virus, the Norovirus can accumulate point mutation in the outer capsid wall which may result in unique immunoglobulin binding sites (18). Therefore, this antigenic drift will result in the formation of new strains of Norovirus and will require the reformation of the vaccines annually (39). Epidemic surveillance using recent updated epidemiological data will allow the identification of predominant strains and identifying a reference vaccine strain each year, similar to the situation of that of the influenza virus (38). Studies on the testing of vaccines are still at an early stage and much work still has to be done.

Treatment

As discussed above, the symptoms caused by Norovirus are generally mild and self-limited and resolves itself. Currently, there is still no specific treatment for a Norovirus infection apart from letting the infection run its course. Individuals who come down with Norovirus illness do not necessarily need to visit a doctor. Instead, the individual should stay home, to prevent the illness from passing to other people in a community, take paracetamol when necessary to relieve any symptoms or fever and most importantly, oral rehydration, by drinking plenty of water to replace the fluid lost through diarrhoea and vomiting. If an individual is having problems to retain fluids, he/she should try to take in small sips more frequently to ensure one is rehydrated. Rehydration solution can also be consumed to restore all the salts and minerals which were lost during diarrhoea and vomiting. This rehydration solution normally comes in powder form which can then be added with water for drinking. For individuals who are suffering from severe dehydration, immediate hospitalization is necessary. Fluids should then be given directly into the body by a naso-gastric tube or intravenously. Antimotility agents such as Loperamide may be useful in helping to regulate diarrhoea in individuals with severe symptoms. Opioids are also useful in regulation of diarrhoea by reducing peristalsis. Anti-emetics such as Chlorpromazine, Acepromazine and Metoclopramide may be useful in helping to control vomiting by inhibiting the D2, Dopamine receptors which are found on the chemical trigger zone of the brain. Individuals suffering from Norovirus illness are advised to consume a light diet of foods that are easily digested, such as soup, rice, pasta and bread, but babies should be given their normal feed throughout (102). It has been shown that interferon and ribavirin can effectively inhibit the replication of Norovirus in replicon-bearing cells (40), but their potential therapeutic value needs to be further investigated. Currently, there are still no anti-viral medications to treat Norovirus. Future research to locate the site of the gastrointestinal tract where the virus replicates may result in development of more specific antiviral therapies targeting the viral replication process. The drugs stated above are only used to control symptoms of Norovirus infection. However, due to the continuous advancement of the field of medicine, all these may change, and once the virus can successfully be propagated in laboratories, studies on them can be conducted which may finally lead us to a cure for Norovirus.

Health impact of Norovirus outbreaks in the coming era

Norovirus would be with mankind for years to come and even though a vaccine is in the process of being developed, it will require a few more years for it to be perfected. In this era of globalisation, travelling has become a norm in our lives. Every year, it is estimated that approximately 1 billion people travel around the globe for various purposes. Travellers may include tourists, business people, soldiers, refugees, migrants etc. Therefore, from a virus perspective, there will be a linkage of people all around the world with plenty of susceptible individuals which can be infected. For example, through air travel, the virus can be passed on from one continent to another, within a couple of days, and this can result in a pandemic.

Currently, travel industry has increased by leaps and bounds. Planned vacations are almost the norm for everyone. Travellers especially vacationers inflicted with Norovirus will almost certainly ruined their travelling plans. On cruise ships or other confined environments, outbreaks of Norovirus can literally bring all leisure activities to a standstill.

As global warming continues to be abated, natural disasters like hurricanes, typhoon, and floods appear to be common events. Congregation of people in crowded relief centres, like what happened during the Katrina Hurricane disaster, will form fertile ground for Norovirus to spread. Failure to control the outbreaks will compound the calamites (disasters) and disrupt relief effort.

Lastly, as the world is rapidly greying especially in the developed countries, many old aged people will be housed in nursing homes. These confined homes are again sitting duck for Norovirus to strike. As the morbidity and mortality of old people are much worse in Norovirus infection, outbreaks could prove disastrous to these cohorts of greying population.

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Cannon RO, Poliner JR, Hirschhorn RB, Rodeheaver DC, Silverman PR, Brown EA, Talbot GH, Stine SE, Monroe SS, Dennis DT and Glass RI. A multistate outbreak of Norwalk virus gastroenteritis associated with consumption of commercial ice. J. Infect Dis. 1991; 164:860-863.
Graham DY, Jiang X, Tanaka T, Opekun AR, Madore HP, Estes MK. Norwalk virus infection of volunteers: new insights based on improves assays. J. Infect. Dis 1994; 170:34-43.
Inouye SK, Yamashita SY, Yoshikawa M, Kato N, Okabe N. Surveillance of viral gastroenteritis in Japan: paediatric cases and outbreak incidents. J. Infect. Dis 2000;181:S270-74.
Adler JL, and Zickl R. Winter vomiting disease. J. Infect. Dis. 1969;119:668-73.
Nilsson M, Hedlund KO, Thorhagen M, et al. Evolution of human caliciviruses RNA in vivo: accumulation of mutations in the protruding P2 domain of the capsid leads to structural changes and possibly a new phenotype. J. VIrol 2003;77(24):13117-24. [PubMed:14645568]
Caul EO. Small round structured viruses: airbourne transmission and hospital control. Lancet 1994; 343:1240-41.
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Teunis PF, Moe CL, Liu P, et al. Norwalk virus: how infectious is itJ Med Virol 2008;80:1468-76.
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Estes MK, Prasad BV, Atmar RL. Noroviruses everywhere: has something changedCurr. Opin. Infect. Dis. 2006;19:467-474.
Mattner F, Sohr D, Heim A, Gastmeier P, Vennema H, Koopmamns M. Risk groups for clinical complications of Norovirus infections: an outbreak investigation. Clin Microbiol Infect 2006;12:69-74.
Harris JP, Edmunds WJ, Pebody R, Brown DW, Lopman BA. Deaths from Norovirus among the elderly, England and Wales. Emerg Infect Dis 2008; 14:1546-52.
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Agus SG, Dolin R, Wyatt RG, Tousimis AJ, Northrup RS. Acute infectious nonbacterial gastroenteritis: intestinal histopathology: histologic and enzymatic alterations during illness produced by Norwalk agent in man. Ann Intern Med 1973;79:18-25.
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Yee EL, Palacio H, Atmar RL, Shah U, Kilborn C, Faul M, Gavagan TE, Feigin RD, Versalovic J, Neil, FH, Panlilio AL, Miller M, Spahr J and Glass RI. Widespread outbreak of Norovirus Gastroenteritis among evacuees of Hurricane Katrina residing in a Large “Megalshelter” in Houston, Texas: lessons learned for prevention. C Dis Cont. 2007;44:1032-39.
Widdowson MA, Cramer EH, Hadley L, et al. Outbreaks of acute gastroenteritis on cruise ships and on land: identification of a predominating circulating strain of Norovirus- United States, 2002. J Infect Dis 2004;190:27-36. [Erratum, J Infect Dis 2004;190:2198.]
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Websites

Richard H.Replication of Polio, Rhino and other Picornaviruses [Internet]. Available from: http://www.pathmicro.med.sc.edu/virol/polio.htm
Treating norovirus infection [Internet]. Available from: http://www.nhs.uk/Conditions/Norovirus/Pages/Treatment.aspx

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Free Essays

Examine how Valvular heart valve disease has caused a major problem worldwide

Introduction:

Valvular heart valve disease caused a major problem worldwide, result in increasing rate of morbidity and mortality (Rashid et al., 2004). Each of the four valves of heart can be affected by dysfunction (Mol et al., 2009). The common solution is the replacement of diseased valves either mechanical or bioprostheses. However, they are associated with shortcoming. Patients with mechanical valves are associated with long term of anticoagulation therapy which leads in higher risk of complications (Hjortnaes et al., 2009). Bioprosthetic valves are less durable, enable to grow and repair and lead to calcification. Moreover, they are associated with reoperation especially with young patients. None of these valves are capable to restore native valves functions.

To overcome replacement shortage of heart valve, in the mid of 1980s in the USA, tissue engineering concept was proposed as alternative solution and has the capability to produce autologous heart valves (Matsumura, 2003).

Definition:

Tissue engineering of heart valves is “manipulation of biological molecules and cells for the purpose of creating new structures capable of metabolic activity”. (Vesely, 2005).

Approaches:

Worldwide, two main approaches have been used to achieve the desirable and clinical needs of heart valves; regeneration and repopulation (Vesely, 2005).

In the first approach, decellularized xenograft (ECM proteins; collagen or fibrin) or allograft served as valve biological scaffold, mixed with autologous cells (myofibroblast and endothelial) has been seeded in vitro (Mendelson and Schoen, 2006), (Neuenschwander, 2004).

However, limitations of this approach are; the construct lack the ability to grow, long term mechanical properties could alter physical properties of the native valves and a possibility of disease transmission (Neuenschwander, 2004). Moreover, inflammatory reaction due to ECM proteins used may deteriorate the scaffold result in biomechanical damage (Mendelson and Schoen, 2006).

A biodegradable synthetic scaffold is the traditional approach in which cells of a specific phenotype are transplanted onto a bioresorbable scaffold in the shape of heart valves (Vesely, 2005).These biocompatible materials offer several advantages; Due to degradation products, they have neither side effects nor immunogenic reactions. They are harmless and easy to handle. At the site of implantation, the remaining autologous living structures after complete biodegradation of the scaffolds have the ability to remodel, to adapt and to grow (Neuenschwander, 2004).

The danger of the transmission of new infections and immunogenic reactions is minor as a result of utilization of autologous cells which lead to identical bioengineered tissues to host cells (Neuenschwander, 2004).

Extracellular matrix material is formed by the cells after attachment and the polymer scaffold degrades (Fuchs et al., 2001).

As shown in (Shinoka et al., 1995) mixed cell population of endothelial cells and from ovine arteries were isolated and separated from each other by fluorescence-activated cell sorting. An acetylated low-density lipoprotein marker was used to label endothelial cells. Myofibroblasts were seeded onto polyglycolic acid scaffolds which then seeded with endothelial cells. Before new tissues being regenerated, the degrading scaffold cannot tolerate pressures of the left ventricle (Vesely, 2005). Therefore, the constructs were implanted in sheep in place of the native right posterior leaflet of the pulmonary valve. This approach results in trivial pulmonary regurgitation in autografts but moderate in allografts and doesn’t show stenosis (Shinoka et al., 1995).

Repopulation is the less popular approach. Complex structure (collagen) is fabricated by manipulating biological molecules. Prior to implanting, cleaning off the porcine aortic valve from cells is required, and leaving intact the connective tissue matrix. Then, the acellular matrix of the patients’ cells is repopulated, stimulated and thus result in creating a living tissue resemble to the native tissue (Vesely, 2005).

Cellular sources:

In tissue engineered valve applications, mesenchymal stem cells and differentiated tissue-specific cells (including circulating endothelial progenitor cells or smooth muscle cells) are the two main types used. They are harvested from either patients or experimental animals (Vesely, 2005). Stem cells along with the appropriate matrix are expected to provide a broader source of either autologous or allogenic cell lines once differentiated to the proper end point. Thus, they are beneficial for therapeutic use in the cardiovascular field (Vesely, 2005).

Animals’ tissues such as canine and pigs are conducting in a research with variability in successful implantation. Mesenchymal stem cells for TE of ECM scaffolds have been obtained from canine tissues. Also, due to presence of type 1 and IV collagen and fibronectin, ECM from pig’s tissues showed ability to grow to a single layer (Rashid et al., 2004).

In most approaches, veins (saphenous vein) or peripheral arteries (radial artery, mammary artery) are efficient sources of cells. Mixed vascular cell populations give rise to myofibroblast and endothelial cells lines. myofibroplasts derived from arteries show decreased proliferation in monolayer culture and ECM formation when cultivated on three dimensional structure compared to cells obtained from veins (Neuenschwander, 2004).

Another promising alternative source of heart valves can be derived from progenitor cells derived from peripheral blood and bone marrow cells (mesenchymal stem cells). MSC can be differentiated into different tissues, are easy to obtain, shows high proliferating capacity in vitro and faster growing than vascular derived cells.

They produce well developed ECM after cultivation under bio-mimetic conditions (Neuenschwander, 2004).

Biomaterials:

There are two principal choices of scaffold; naturally or synthetic polymeric scaffolds. Exogenous ECM scaffolds are required to provide mechanical support until the target newly tissue is formed and become stable. Designing is based on the target cells population needed to implant at the injury or diseased sites. In vivo, they are degraded alongside the implanted functionally tissues grow and organize their matrix structure (Kim et al., 2010).

Non-toxic, biodegradable and biocompatible scaffolds serve as a temporary matrix for the seeded cells due to their own a highly porous microstructure that supply nutrients required for growth and necessary for waste removal. They possess structural integrity to withstand in vitro and in vivo loading. The most widely used in HVE are polyglycolic acid (PGA), polylactic acid (PLA) and their copolymers (PGLA). PGA is highly resorbable, linear, a highly crystalline and have a high melting point. PLA reduce the rate of hydrolysis and have limited water uptake. In all of that, to facilitate tissue growth, growth factors are integrated in the scaffold. However, a number of disadvantages must be overcome; slow or incomplete degradation that cause inflammation, limited nutrients and oxygen delivery to deep cells and fibrosis (scar) occupied the space formed after scaffold degradation (Mendelson and Schoen, 2006).

Natural scaffold composed of decellularized xenograft or allograft tissue or ECM components such as collagen or fibrin (Mendelson and Schoen, 2006). Fibrin gel scaffold can be designed into a valve structure to form a biodegradable, autologous scaffold. Blood is the source of fibrin gel and mould into autologous manner to work against immunogenicity. Seeding cells into fibrin scaffold results in good tissue development with viable fibroblast. However, fibrin scaffold would lack mechanical strength (Knight, 2004). Furthermore, in a process similar to the contraction of a wound healing, cells entrapped in collagen gels compact the gel, improve their property and increase density (Mendelson and Schoen, 2006). But, any scaffold made from collagen alone would like to degenerate very quickly due to in vivo forces affected heart valves (Knight, 2004). Moreover, hyaluronan is a glycosaminoglycan polymer with a repeating disaccharide structure and being used as biocompatible material ECM scaffold. It imparts viscoelastic properties and applies pressure that gives tissues compressive resistance (Vesely, 2005).

Sterilization methods:

Several methods are used to sterile materials utilized in process of seeding and tissue harvesting. 1) Dry heat sterilization in which items are placed in an oven for one hour at 160T to be sterilized by dry heat. 2) Moist heat sterilization is used to autoclave objects and solutions not suitable for dry heat sterilization for 20 minutes at 121 T, 15 pounds per square inch (psi). 3) 0.2ptm filters are used to sterilize solutions not suitable for autoclaving (Knight, 2004).

Pre-clinical trials:

Animal model is an essential part of biomedical research to approve tissue engineered devices by FDA in order to carry on clinical trials. Using animal tissues as sources relies on many factors; cost, ethical considerations, availability and the nature of the tested tissue. In Zilla study (Zilla et al., 1994), baboons were used to study the proliferation of seeding (endothelial cells) EC on polytetrafluoroethylene (PTFE) grafts. Compared to the control of unseeded graft, seeded graft showed persistent confluent EC layer through time with the aid of fibrin glue enriched with RGD (Zilla et al., 1994).

Due to similar anatomy and physiology to that of humans, pigs have been used widely for experimental study. Also, they are cooperative without general anesthesia. They are capable of rabid growth so limiting the time required for TE construct (Rashid et al., 2004).

Biodegradable polyglycolic acid (PGA) scaffold was treated by sodium hydroxide and modified seeded bovine SMC and EC were used by Niklason and co-workers in after 24 days of implantation in swine model.

Ovine and caprine are also models to study TE due to large size and easy access to the carotid artery in the long neck. They can be used for long term study because adult animal can’t grow (Rashid et al., 2004). In a number of researches, sheep model was used widely but ordained for failure as a result of exuberant fibrotic response to implants (Vesely, 2005). Compared to humans, implants grow rapidly with fibrotic tissue in sheep (Schoen, 2011).

In preclinical testing, the choice of animal model is a challenge owing to immunologic considerations (Mendelson and Schoen, 2006).

Biomechanical culture:

Various parameters determine the optimal conditioning protocols; the scaffold, the magnitude and types of mechanical cues, the sensitivity of cell to the used scaffolds. Bioreactors in TEHV have been developed to improve tissue formation, organization and functions and to stimulate dynamic mechanical of the TEHV. Moreover, to mimic native excitation-contraction coupling, electrical stimulation has been used. Additionally, to mimic the diastolic phase of the cardiac cycle, a diastolic pulse duplicator bioreactor has been developed which result in dynamic tissue straining (Sacks et al., 2009).

Commercialized products:

In October 2000, CE Mark approved use of the CryoLife Synergraft. It was similar to decellularization matrix approach by removing cellular antigens using extraction and dissolution. It was expected to sound mechanically as acellular matrix. Unfortunately, complications related to stenosis, inflammation and valve rupture result in death and thus withdrew from the market (Vesely, 2005).

Challenges:

Till date, no EHV constructs have been commercialized. Before translation of the construct to patients, numerous steps must be considered and assured laboratory. For example; ethical issues, safety, efficacy and quality of the product should be evaluated. Additionally, medical devices interactions results such as; thrombosis, infection and inflammation will have to be accepted. There is a need to develop tools to monitor the fate of transplanted and endogenous cells, biomarkers to evaluate the patient’s variability to implantation. in all of that, suitable approach is required that ensure efficiency and safety (Schoen, 2011).

Conclusion:

Three main issues determine the success of tissue engineered heart valve; 1) sources of cells, 2) the (matrix) scaffold that serves as a guiding structure and determines the three dimensional shapes of tissue development and cell attachment and 3) the optimal culturing condition for cell growth. State of art of TEHV today is still on research, significant challenges must be solved before start in clinical application.

REFERENCES:
FUCHS, J. R., NASSERI, B. A. & VACANTI, J. P. 2001. Tissue engineering: a 21st century solution to surgical reconstruction. The Annals of thoracic surgery, 72, 577-591.

HJORTNAES, J., BOUTEN, C. V. C., VAN HERWERDEN, L. A., GRUNDEMAN, P. F. & KLUIN, J. 2009. Translating autologous heart valve tissue engineering from bench to bed. Tissue Engineering Part B: Reviews, 15, 307-317.

KIM, B. S., PARK, I. K., HOSHIBA, T., JIANG, H. L., CHOI, Y. J., AKAIKE, T. & CHO, C. S. 2010. Design of artificial extracellular matrices for tissue engineering. Progress in Polymer Science.

KNIGHT, R. L. 2004. Development of methods for the tissue engineering of cardiac valves using mesenchymal stem cells.

MATSUMURA, G. 2003. Successful application of tissue engineered vascular autografts: clinical experience. Biomaterials, 24, 2303-2308.

MENDELSON, K. & SCHOEN, F. J. 2006. Heart Valve Tissue Engineering: Concepts, Approaches, Progress, and Challenges. Annals of Biomedical Engineering, 34, 1799-1819.

MOL, A., SMITS, A. I. P. M., BOUTEN, C. V. C. & BAAIJENS, F. 2009. Tissue engineering of heart valves: advances and current challenges. Expert Review of Medical Devices, 6, 259-275.

NEUENSCHWANDER, S. 2004. Heart valve tissue engineering. Transplant Immunology, 12, 359-365.

RASHID, S. T., SALACINSKI, H. J., HAMILTON, G. & SEIFALIAN, A. M. 2004. The use of animal models in developing the discipline of cardiovascular tissue engineering: a review. Biomaterials, 25, 1627-1637.

SACKS, M. S., SCHOEN, F. J. & MAYER JR, J. E. 2009. Bioengineering challenges for heart valve tissue engineering. Annual Review of Biomedical Engineering, 11, 289-313.

SCHOEN, F. J. 2011. Heart valve tissue engineering: quo vadisCurrent Opinion in Biotechnology.

SHINOKA, T., BREUER, C. K., TANEL, R. E., ZUND, G., MIURA, T., MA, P. X., LANGER, R., VACANTI, J. P. & MAYER, J. E. 1995. Tissue engineering heart valves: valve leaflet replacement study in a lamb model. The Annals of thoracic surgery, 60, S513-S516.

VESELY, I. 2005. Heart valve tissue engineering. Circulation research, 97, 743.

ZILLA, P., PREISS, P., GROSCURGH, P., RoSEMEIER, F., DEUTSCH, M., ODELL, J., HEIDINGER, C., FASOL, R. & VON OPPELL, U. 1994. In vitro-lined endothelium: initial integrity and ultrastructural events. Surgery, 116, 524-534.

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Free Essays

Squamous cell carcinoma of the head and neck region: Pathophysiology & management of the disease

1.0. Introduction

Head and Neck cancer is increasingly becoming a very serious public health issue in the world, correlated with high incidence and mortality rates mainly in developing countries(Jeffries and Foulkes 2001). Deformities caused by the malignancy such as facial and neck injuries profoundly affect the individual’s social and emotional well being (Murphy et al. 2007).

1.1 Epidemiology:

90% of all head and neck cancers are squamous cell carcinomas (Peedell 2005). According to the statistical data (Figure 1) published in 2002 by cancer research UK, shows a considerable variation in the incidence of Head and neck squamous cell carcinomas (HNSCC) around the world. HNSCC accounts for 4% of all cancers in the UK, currently ranked as the sixth most common cancer type worldwide with 650,000 estimated new cases and 350,000 deaths per year (Argiris et al, 2008). According to recent epidemiological studies in the Indian sub continent, the condition has been reported to constitute 30% – 40% of all other malignancies (Bhattacharya et al. 2005). Cohort studies by Souhami and Tobias, (2005) have shown the malignancy to be more common in men than women by the ratio 3:1 indicating a higher male incidence than women (see Table 1).

Cancer siteIncidence rate (2007)Death rate (2008)
MaleFemalePeopleMaleFemalePeople
Nasopharyngeal167742418437121
Oral :LipMouthOropharyngealTongue3,5941911,0008121,0611,816816952725815,4102721,6951,0841,6421,153610265278343669112281072011,82221493385544
Larynx1,8443612,205685164849

Table 1: Showing the latest UK incidence and mortality rate of the squamous cell carcinomas of various head and neck regions adopted from cancer research UK on 15/04/2011. http://info.cancerresearchuk.org/prod_consump/groups/cr_common/@nre/@sta/documents/generalcontent/crukmig_1000ast-2735.pdf .

Figure1: Showing incidence of HNSCC in different countries in 2002. Adopted from Cancer Research UK on 15/04/2011/. http://info.cancerresearchuk.org/cancerstats/types/oral/incidence/

1.2 Aetiological factors of HNSCC:

A relatively diverse number of aetiological agents have been linked to the incidence of HNSCC. Epidemiological studies have shown an association of both environmental and genetic factors (Evans et al, 2006).

Environmental factors: Chronic tobacco smoking, excessive alcohol consumption, chewing betel nut, leaf and quid, inhalation of paint fumes, plastic by-products, wood dust and continual exposure to asbestos have all shown inductive activity in the cancer genesis (Mondal et al. 2003). Machado et al. (2010) stated that, increasing evidence shows association of Human Pappilloma virus (HPV) especially type 16 and 18 to the incidence of oropharyngeal carcinoma through the expression of E6 and E7 oncoprotein. A strong association of Epstein Barr Virus (EBV) to nasopharyngeal carcinoma has been shown by Goldenberg et al (2001) through in vivo studies.

Genetic factors: Substantial numbers of genetic factors have been identified to have an inductive effect to the genesis of HNSCC. Translocation in chromosome 8p24 is a very common event in the ontogenesis of HNSCC as it is involved in the amplification of MYC proto-oncogene (Nilanjana et al. 2005). According to mondal et al. (2003) allelic deletions in chromosome 11q21-24 and p13-15 have increasingly been linked to the incidence of SCC of the oral cavity, larynx and orofacial regions (Table 2.1). Nonetheless, increasing studies have emerged associating racial differences to incidences of particular HNSCC such as pharyngeal and oral cavity SCC (National cancer institute) (see Table 2.2).

Aetiological factors of HNSCC

Table 2.1: showing aetiological factors of head and neck cancer adopted from (Evans et al, 2006).

Table 2.2: showing the US incidence and death rate of oral and pharyngeal carcinoma in both males and females of different racial origins adopted from National cancer institute on 28/04/11. http://www.cancer.gov/cancertopics/types/throat

1.3 Clinical Signs and Symptoms of HNSCC

HNSCC presents distinct signs and symptoms depending on the primary sites of origin. Generally malignant ulcerations of the surface mucosa, enlargement of adjacent lymph nodes in particular regions may be detected. In the Oral cavity, unhealing sores or ulcer may be prominent, ear pain experienced on side of the lesion and indurate ulcer may be felt during palpation, whereas, in the larynx, continual hoarseness in the voice, ear pain emanates from outside the ear and difficulty breathing with a stridor. Symptoms in the nasal and paranasal sinuses include nasal obstruction, bloody nasal discharge and facial swelling accompanied with pain as well as diplopia (visual impairment). Patients with Nasopharyngeal carcinoma experience prominent obstruction of the nostrils and nasal blood discharge, neurological problems due to cranial nerve involvement, and possibility of deafness due to obstruction of the eustachain tube. (Rubin, 2001). Oropharyngeal tumours present symptoms at a later stage, a feeling of discomfort in the throat when swallowing and radiating pain to the ear is exhibited, a mass in the neck may be visible but at a much later stage. Hypopharyngeal carcinomas may present vague symptoms such as discomfort during swallowing which progresses to dysphagia, radiating pain to the ear, respiratory obstruction and hoarseness in the voice occurring at a later stage (Horwich 1995).

1.4 Anatomy of the head and neck

The head and neck is made up of complex structural organs subjected to distinctive roles. It contains four major intrinsic cavities; the oral cavity, nasal cavity, pharyngeal cavity and laryngeal cavity (See figure 2). The framework of these cavities is bony and cartilaginous to which muscles and connective tissues attach, covered by a lining of squamous epithelial cells (Johnson and Jacobson, 2006).

Figure 1.1: Showing the anatomy of the head and neck adapted from web calf : http://www.webcalf.com [Accessed on 06/04/11]

1.4.1Pharynx:

Consists of two distal sphincters that help to channel food and air to the right direction .The organ is divided into three anatomical parts. The Nasopharynx, an organ located behind the nasal cavity which extends from the base of the skull to the upper part of the soft palate below. Second is the oropharynx, situated behind the oral cavity including the soft palate, posterior third of the tongue, uvula, faucial pillars and tonsils. Thirdly, the hypopharynx located behind the larynx and extends from the floor of vallecula suclus above to the level of the lower border of the cricoid cartillage where it joins the eosophagus. (Souhami and Tobias, 2005).

Figure 1.2: showing the Normal Anatomy of pharynx adopted from clinic- clinic. http://www.clinic-clinic.com/images/pharynx.gif [accessed: 29/04/11]

1.4.2 Larynx:

Is an essential organ in speech production and also acts as a protective sphincter to keep the lower part of the respiratory tract free from any foreign bodies. The larynx extends from the epiglottis and valleculae superiorly to the lower border of the cricoid cartillage inferiorly (Johnson and Jacobson, 2006). It divides into three interrelated regions, the glottis (middle of the vocal cords separating the true and false vocal cords), supraglottis (above the vocal cords containing the epiglottis) and subglottis (below the vocal cords horizontal to the true vocal folds) (Souhami and Tobias, 2005). (See figure 2.2)

Figure 1.3: showing cross sectional diagram of larynx adapted from Wigston choir: http://www.wigstonchoir.org.uk/images/larynx.jpg [Accessed on 29/04/11].

1.4.3 Oral cavity:

Extends from the skin vermilion (line that separates between the lips and skin) junction of the lips to the soft and hard palates above and to the line of the papillae on the tongue below which includes the lips, two thirds of tongue, floor of mouth, hard palate, buccal mucosa and the lower alveolus(figure 2.3) (Neal & Hoskin, 2005).

Figure 1.4: showing the anatomical structure of oral cavity adapted from BlogSpot: http://learn-free-medical-transcription.blogspot.com/2009_02_24_archive.html [Accessed on 6/04/11]

1.4.4 The nasal cavity and paranasal sinuses:

The nasal cavity is a large air filled space behind the nose where air passes on the way to the throat. Paranasal sinus are four paired air filled areas that surround the nasal cavity in the cheeks above and between the eyes and behind the ethmoids ( maxillary sinuses, frontal sinuses, ethmoid sinuses and spenoid sinuses) (Dubey et al. 1999) ( see Figure 2.4)

Figure 1.5: showing a cross sectional view of the nasal cavity and paranasal sinuses adopted from Cancer research UK http://www.cancerhelp.org.uk/type/nasal-cancer/about/the-nasal-cavity-and-paranasal-sinuses. and Health all refer http://health.allrefer.com/health/foreign-body-in-the-nose-nasal-anatomy.html [Accessed on 29/04/11]

1.4.5 Types of HNSCC:

HNSCC are heterogeneous malignant tumours arising from previously mentioned structures of the head and neck region lined with squamous epithelial cells. The tumours are categorised according to the anatomical regions of origin such as the, larynx (laryngeal carcinoma, pharynx (pharyngeal carcinoma), oral cavity (carcinoma of oral cavity), nasal cavity (carcinoma of nasal cavity) and paranasal sinuses (carcinoma of paranasal sinuses) (Black et al) where they demonstrate significant biological and clinical neoplastic behaviours (Patmorea et al.2007).

Aims and Objectives:

Aim:

The aim of this project is critically analyse the Pathophysiology of head and neck squamous cell carcinoma and how the disease is managed.

Objectives:

Review different literature sources in order to provide a comprehensive analysis of the Pathophysiology and the management of HNSCC.

Explore different treatment procedures used in managing the disease.

2.0. Pathophysiology of Head and Neck Squamous cell carcinoma

The pathogenesis of HNSCC appears to evolve through complex multistage processes involving alteration of molecules that regulate cellular signalling pathways in DNA damage response, cell cycle arrest and apoptosis (Figueiredo et al, 2004). Chronic exposure to risk factors such as, carcinogenic agents in tobacco and alcohol or HPV through expression of transforming oncoprotein E6 and E7 has shown to have an alterative effect in the molecules, resulting in DNA mutation hence, uncontrolled cell proliferation. (Evans and Powell, 2010)

HPV: E6 oncoprotein gene targets P53 gene for degradation and therefore prevents controlled death of abnormal cells whereas E7 gene inactivates Rb (retinoblastoma) function which results in abnormal cell proliferation and disturbs the normal cell cycle regulation (Wang, 2007)

Carcinogens: Damage the DNA causing accumulation of DNA abnormalities within the cell, resulting in alteration of stem cell maturation, differentiation and disturbance in the regenerative processes, hence the appearance of malignant transformed cells (klonisch et al. 2008).

Persistent cell proliferation in the affected region results in a local mass of abnormal cells producing degradative enzymes in the presence of motility factors enabling the tumour cells to metastasize to adjacent or deeper tissues (Leemans et al.2010) and (Evans et al. 2003). (See flow diagram 1.6)

Normal cell Persistent genetic damageSomatic mutationInvasiveness VascularisationTumour formationMetastasis

Figure 1.6: Showing the development of metastasizing cancer adapted from Tobias et al, (2010).

2.1. Hypopharyngeal Carcinoma:

Carcinomas of the hypopharynx are very uncommon tumours, highly lethal and demonstrate a diffuse local spread and a natural history of early distant metastasis, hence a poor 5 year prognosis ranging between 10% – 20% (Nassar and Ibrahim, 2007). Alterative effect of carcinogens on the p53 gene in the mucosa causes premalignant mucosal lesions to develop into hyperproliferative lesions, acquiring the ability to metastasize and invade local structures, lymphatics then spreads to regional lymph nodes and invading vascular channels gaining access to other organs. (Chien et al, 2003) (see. figure 2.5). According to studies by Hattori et al, (2000), minimal association of p53 mutation and exposure to carcinogens has been linked in the incidence of second primary hypopharyngeal carcinomas.

Figure 1.7: showing the metastatic spread of hypopharyngeal carcinomas adopted from cancer clinical trials http://www.cancertrialshelp.org/blog/wp-content/uploads/2010/10/Throat-cancer-stage-4c.jpg [Accessed on 28/04/2011].

2.2. Oropharyngeal Squamous cell carcinoma (OPSCC):

Oropharyngeal carcinomas are usually seen as large primary tumours or post metastasis to regional lymph nodes but rarely seen at early stages with high incidences commonly seen in patients in their fifth or seventh decades (selek et al. 2004). Human Papillomavirus type 16 and 18 have been linked to the increased incidence of OPSCC. The virus affects the transitional epithelium of the upper aerodigestive tract, integrating the viral DNA into the host DNA. Also viral RNA and oncogenic proteins such as E6 and E7 facilitate in the disruption of vital tumour suppressor genes p53 and Rb which enables the tumour cells to proliferate and metastasize to different organs of the body (see fugure 2.6) (Van Monsjou et al. 2010). However according to Pezier and Patridge, (2011) HPV related OPSCC is associated with improved survival rate compared to non-HPV SCC because they show high sensitivity to chemotherapy and radiotherapy.

Figure 1.8: Showing the metastatic spread of oropharyngeal carcinomas adopted from cancer clinical trials. http://www.cancertrialshelp.org/blog/wp-content/uploads/2010/10/Throat-cancer-stage-4c.jpg [Accessed on 28/04/2011]

2.3. Laryngeal carcinoma:

Carcinogenesis is induced by DNA mutation as a result of exposure to carcinogenic substances leading to a progressive accumulation of genetic alterations in the normal epithelial cells lining the larynx, consequently leading to a selection of clonal population of transformed malignant cells in the region (Ha and Califano, 2002). The Extracellular matrix (ECM) provides a frame work or site which contributes to series of cellular events such as proliferation, adhesion, differentiation, regulating tissue repair and metastasis. Within the ECM are two proteogylcans with contradictory roles, versican and decorin. Versican directly or indirectly regulates cell adhesion, migration and proliferation whereas decorin effectively inhibits tumour cell growth through indirect inhibition of tumour cell growth factor receptors. However, during the progression of laryngeal carcinoma, both proteins undergo alteration resulting in a change to the structural composition of the interstitial ECM which aids in the metastatic spread of cancer through access to the lymphatics and systemic circulation, therefore presenting phenotypic laryngeal cancerous lesions (Skandalis et al. 2006).

2.4 Carcinoma of the Nasal cavity and paranasal sinuses

Nasal cavity and paranasal sinus carcinomas manifest similar clinical signs and symptoms strongly linked with exposure to occupational chemicals such as nickel and chromium dust (Cancer research UK). Carcinoma of the paranasal sinuses particularly in the maxillary region tend to be more common than that of the nasal cavity characteristically known for rapid growth and extensive local destruction (Shindo et al, 1990). It grows within the bony confines of the sinuses but rarely presents any symptoms until it metastasizes to adjacent regions (Mendhall and Pfister, 2008). According to Dubey et al (1999), the lethality and the poor prognosis of the malignancy is directly linked to the trivialised early presented signs and symptoms often confused with inflammatory conditions, hence it’s late diagnosis. Studies by Alos et al, (2009) proved that patients who are HPV positively associated with the condition carry a better prognosis than HPV negative patients.

3.0 Diagnosis of Head and Neck Squamous Cell Carcinomas

HNSSC may display vague signs and symptoms hence, early detection is very crucial in the disease diagnosis and management. It limits morbidity of treatment and increases the chances of cure (Haddad et al. 2008). A multidisciplinary diagnostic approach may be considered depending on the location or severity of the condition. Diagnostic procedures used may be categorised into three groups; Physical examination, laboratory diagnosis and imaging diagnostic techniques.

3.1 Physical examination

3.1.1 Inspection and palpation:

Inspection and palpation serve as the initial steps in the diagnosis of head and neck cancers especially oral cavity and oropharyngeal carcinomas for presence of any lump as a indication of lymph node involvement (Maurizio and Eckart 2010) (figures 1&2). The procedure also serves crucial in the prediction of metastasis in the affected sites (Martinez-Gimeno et al. 2010). However, as correctly stated by Hang and Hao (2002), in order assign suitable treatment, additional diagnostic techniques should be incorporated rather than palpation alone .

Figures 1.8 and 1.9: shows inspection and palpation of head and neck regions for suspected HNSCC patients adopted from a practical guide to clinical medicine. http://eglobalmed.com/core/PracticalGuideClinicalMedicine/medicine.ucsd.edu/clinicalmed/head.html. [Accessed on 29th/04/2011]

3.3 Imaging Diagnostic Techniques:

3.2.1 Laryngoscopy and Nasopharyngoscopy:

Laryngoscopy is either a direct or an indirect procedure using either a flexible laryngoscope incorporated with a thin fibre optic endoscope or a rigid laryngoscope embodied with a metal tube and angled lens inserted through the mouth to the site of infection (see figure 2.1) (de-Bree et al. 2008). The technique aids the physician to diagnose and asses lesion extension and vocal cord morbidity in patients suspected with hypopharyngeal and laryngeal carcinomas despite being the most difficult sites to examine (Marioni et al. 2005).

Nasopharyngoscopy analogously uses flexible and optical instruments with a long tube fitted with an eye piece, lenses and light source to detect any cancerous lesions such as swellings, bleeding in sites ranging from the nasal passage to the larynx (Mackie et al. 2000).

Figure 2.1: Showing rigid laryngoscope inserted through the mouth adopted from Nucleus medical media http://iv.nucleusinc.com/generateexhibit.php?ID=8128&ExhibitKeywordsRaw=&TL=&A=1029 [Accessed 28/04/2011]

3.2.2 Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) Scan:

The detailed anatomical pathological data obtained using CT and MRI scans makes the imaging procedures the prime methods of choice in diagnosing suspected or proven head and neck carcinomas for subsequent clinical management (Petrou and Mukherji 2008).

CT Scan:

One of the most preferred and frequently used diagnostic imaging tools for HNSCC. It uses x-ray beams in order to provide detailed and accurate images of the site under examination, indicating the extent and size of the tumour which may guide the radiologist in performing further test such as biopsy (Daisne et al. 2003).

MRI Scan:

A very reliable diagnostic technique which uses strong magnetic fields and radio waves to produce detailed thin sliced images of the affected region showing metastatic spread (Manavis et al. 2005). Generally preferred over CT scan and primarily used in diagnosing tumours confined in the oral cavity, but less often used than CT, except in cases where additional detail is required and no better non invasive methods available (Rumboldt et al 2006). However as stated by hoshikawa et al. (2009) the preceded imaging techniques have limited capabilities in assessing therapeutic effects of treatment therefore difficulty arises in detecting recurrent tumours at a early stage.

PET (Positron Emission Tomography) scan however, unlike CT and MRI has been shown to offer higher sensitivity for imaging of treated head and neck cancers (Rumboldt et al, 2006). The reason being as stated by Passero et al (2010), it assesses metabolic activity within the target lesion hence; it differentiates between normal and cancerous cells.

Figures 2.2 and 2.3: Showing diagnostic uses of CT and MRI scans adopted from magnet lab and health republic on 28/04/2011. http://www.magnet.fsu.edu/education/tutorials/magnetacademy/mri/ and http://healthrepublic.org/CtScan.html

3.3 Laboratory diagnosis.

3.3.1Biopsy:

Is a medical procedure that involves the removal of cells or tissues to determine presence or absence, size and extent of disease spread (Adoga et al, 2009).Tissue biopsy still remains to be an essential requirement in the establishing histological diagnosis and a means of guiding treatment. However, Rumboldt et al, (2006) states that, the procedure acts as a supplement to the preceded physical examination and radiological investigations. Techniques used include open excisional biopsy (OEB), Fine needle aspiration cytology (FNAC), core needle biopsy (CNB) and open surgery biopsy, although OEB and FNAC being the most commonly used methods (Pfeiffer et al. 2009) .

Figure 2.0: showing a biopsy sample taken from a lesion in the oropharynx, adopted from Medical images on 28th/04/2011. http://medicalimages.allrefer.com/large/oropharyngeal-biopsy [Accessed on 28th/04/2011]

4.0Staging of Head and Neck Squamous cell carcinomas

The aforementioned diagnostic procedures prove very crucial in tumour staging and determining factors in designating appropriate treatment regimens and assessing prognosis (Takes, 2004). The presence of tumours in distinct anatomical sites of the head and neck exhibiting diverse clinical behaviours, requires a rigorous staging system (Patel and Shah, 2006).TNM is the preferred and universally accepted staging system for malignant HNSCC designed to describe the anatomical extent of primary tumours (T), nodal involvement (N) and distant metastasis (M) (Van der Schroeff and Baatenburg de Jong, 2009) (Table 2.3). However according to manikantan et al( 2009), despite the system’s positive aspects, numerous controversial flaws have been acknowledged in the system and anticipating changes to improve it’s purpose.

TNM Staging

T – Primary tumor

Tis – Preinvasive cancer (carcinoma in situ)
T0 – No evidence of primary tumor
T1 – Tumor 2 cm or less in greatest dimension
T2 – Tumor larger than 2 cm but not larger than 4 cm
T3 – Tumor larger than 4 cm
T4 – Tumor with extension to bone, muscle, skin, antrum, neck
Tx – Minimum requirements to assess primary tumor cannot be met

N – Regional lymph nodes

N0 – No evidence of regional lymph node involvement
N1 – Evidence of involvement of a movable homolateral regional lymph node smaller than 3 cm
N2a – Evidence of involvement of a movable homolateral regional lymph node 3-6 cm
N2b – Evidence of involvement of multiple homolateral regional lymph nodes smaller than 6 cm
N2c – Evidence of involvement of contralateral or bilateral regional lymph nodes smaller than 6 cm
N3 – Any lymph node larger than 6 cm
Nx – Minimum requirements to assess the regional nodes cannot be met

M – Distant metastases

M0 – No evidence of distant metastases
M1 – Evidence of distant metastases
Mx – Minimum requirements to assess the presence of distant metastases cannot be met

Staging

Stage 1 – T1/N0/M0
Stage 2 – T2/N0/M0
Stage 3 – T3/N0/M0, T3/N1/M0
Stage 4 – Any T/N1/M0, any T/N0/M0, any T/N2/M0, any T/N3/M0, any T/any N/M1

Table 2.3: showing TNM staging procedure used for HNSCC adapted from e medicine http://emedicine.medscape.com/article/1289986-overview. [Accessed on 29th/03/11].

5.0 Clinical Management of Head and Neck Squamous cell Carcinomas.

The diverse non- specific clinical symptoms presented by HNSCC patients at different stages endow the management team with numerous challenges hence, multidisciplinary management teams including; medical and radiation oncologists, head and neck surgeons, pathologists, nuclear medicine physicians endeavour to work together to ensure optimal management of the malignancy. (Fanucchi et al, 2006). The adopted approach may entail using different treatment modalities depending on the staging of the tumour. Single modality treatment such as surgery, chemotherapy or radiotherapy is primarily used for early stage SCC whereas patients with the advanced locoregional malignancy may be treated with combined modalities based on expert opinion (Anthony et al. 2010) (See Flow chart)

5.1 Surgery:

Surgical intervention is the main treatment option commonly used for HNSCC despite the complications that may arise (Kerawala, 2010). Surgery is a very effective treatment procedure in eradicating or reducing tumour burden inspite it’s successful management being influenced by tumour staging which guides adjuvant treatment decisions. Significant effects however could be seen in early staged tumours (T1-T2) primarily in the tongue and other sites of the oral cavity (Scarpa, 2009). Studies by Goda et al (2011) have shown exceptional and durable local control of advanced tumours with adjuvant radiotherapy following surgery. Choe et al, (2010) has also highlighted adjuvant chemotherapy after surgery to be associated with a favourable outcome for locoregionally advanced HNSCC.However, recent studies by Takenori et al. (2011) indicated adjunctive therapy less effective in survival benefit compared to surgery alone. Kumar et al, (2005) in agreement stated that, because acute radiation effects are more severe in combined therapy than in single modality treatments.

5.2 Radiation therapy:

Radiotherapy and surgery serve as the main treatment modalities for HNSCC, however the role of radiotherapy is relatively complex as it can be delivered, with a curative intent to improve local region control post surgery or for palliative use. It results in high tumour control and cure rates for early stage tumours and by default the treatment choice for patients unfit for surgery (Argis et al, 2008). Radiation therapy renders the cell DNA unable to undergo normal mitotic mechanisms causing mitotic death and shrinkage of the tumour as well as preserving the organ involved (Donato et al, 2003). Although single modality radiotherapy can be used for locally advanced tumours, according to studies by Creak et al. (2005), a significant number of patients, post-radiotherapy of approximately 60-70Gy radiation dose showed tumour persistence and recurrence within weeks or months indicating poor tumour response to the therapy. However, combined postoperative administration of chemotherapy (cisplatin) and radiotherapy has shown decreased local and regional recurrence (Cooper et al, 2004)

Figure 2.1: Showing a view of radiotherapy machine adapted from med gadget http://medgadget.com/archives/2008/07/varians_rapidarc_radiation_delivery_system_goes_clinical.html [Accessed on 30th/04/11]

5.3 Chemotherapy:

Chemotherapy is significantly used in different treatment regimens for HNSCC patients particularly with locoregionally advanced tumours (see table 2.4) (Evans et al 2006). The role of chemotherapy varies depending on the stage of the disease, patients with metastatic, incurable locoregional HNSCC, chemotherapy is only palliative (relieving symptoms) whereas patients with potentially curable locoregional disease, chemotherapy acts as an integral component of multimodality treatment approach particularly when the tumour is unresectable and organ preservation is one the main goals of the therapy (Syrigos et al, 2009). A line of chemotherapeutic agents used include 5-flurouracil(5-FU), methotrexate, cisplatin, bleomycin and taxanes, however the standard regimen for HNSCC is combination of cisplatin with 5-FU, approved to induce a response rate of 70%- 88% for organ preservation and 40%-50% for locoregion recurrence (Bhide et al, 2000) . However, retrospective studies by Cruz et al. (2007) have shown a higher activity of new combination regimens with texanes compared to the standard treatment. Despite the enormous benefits, considerable measures aught to be taken such as follow up on patients to confirm presence of any end organ dysfunction as a result of the toxicity yielding side effects such as myelosuppression, neurotoxicity, pulmonary fibrosis, nephrotoxicity, and nausea. (Juneja and Lacey, 2009).

Role of chemotherapy in management of HNSCC

Types of chemotherapyRole

Single modality Curative intent
Neoadjuvant Given prior to loco-regional treatment (radiation or surgery) to reduce tumour burden.
Adjuvant Used following local treatment (surgical or radiation therapy) to minimise recurrence.
Salvage Used after recurrence of refractory tumour following previous treatment
Concomitant Chemotherapy administered simultaneously with radiation therapy to increase radiosensitivty

Table 2.4: showing types of chemotherapy with their roles in managing HNSCC adopted from Evans et al. 2006.

5.4 Combined therapy (chemotherapy and radiotherapy):

The complexity of treatment modalities relatively varies with advancement of the disease, hence the requirement of detailed, careful examination of the patient prior to selection of suitable combination therapy (see table 2.5) (Syrigos et al, 2009). According to Aldelstein (2003), after significant long- term functional deficits and radiation induced long- time toxicities following combination of surgery with radiation therapy. The emergence of chemoradiotherapy as a standard care procedure for HNSCC has proven advantageous in preserving both organ structure and function, therefore used in cases where surgical resection is suspected to cause huge functional and cosmetic defects especially in oropharyngeal carcinomas(see flow chart) (Nagraj et al. 2010). There’s however limited evidence regarding the survival benefit of the combined treatment modality in oral cavity SCC (Day et al. 2003).

Factors to consider prior to selection of combination therapy

Presence of severe co-morbidities and age-related frailty in patientUnderlying severe psychosocial problemsPresence of rapidly growing tumours with advanced nodal involvementLocation of the primary tumourGoals for the therapy (organs preservation, increase quality of life, reduction of metastasis)

Table 2.5: Shows vital factors to consider before selection of combination therapy, adapted from (Syrigos et al, 2009).

5.5 Non-invasive Management Procedures:

The delicacy of the involved regions after invasive treatment may subject the patient to physical and psychological complications (Paleri et al 2010). (Table 2.6) shows a multidisciplinary support management team with techniques which could be substituted or supplemented with the aforementioned management procedures in order to minimise the complications and maximise eradication (see Table 2.6) (Evans et al. 2006).

Clinical nurse specialistDietitianDental hygienist / DentistPsychotherapist / physiotherapistPalliative care teamSpeech and language therapist

Pain and management therapist

Table 2.6: showing different supportive team members in managing HNSCC adapted from Evans et al. (2006).

6.0 Prognosis:

Prognostic measures after treatment are essentially dependent on three factors; Staging, tumour site and modality of treatment (See table 2.5). Nonetheless, a good prospect of long term remission is generally seen in early tumours (T1-T2, N0-N1) ranging between 60 – 90% 5 year survival rates whereas patients at stage 4(T4) with no higher than 30% 5 year survival chance (Obe and Johnston, 2001)

Table 2.7: Showing a 5-year survival rate in different HNSCC adapted from Obe and Johnston (2001).

6.1 Follow up and prevention

Follow after treatment coupled to prognosis is a very essential aspect of patient management as it allows early detection of recurrent and second primary tumours (Joshi et al, 2009). Preventative measures however, are of the upmost importance in improving prognosis and reducing disease occurrence (chen-shuan et al. 2010). According to Silverman, (2001) early detection and patient education as well as the general public of the malignancy, is a crucial step in disease management. However, a questionnaire studies by Joshi et al, (2009) have shown little survival benefits achieved from patient follow ups.

7.0 New Research and Innovation:

A great deal of research has been endowed in developing better treatment procedures. The use of endoscopic laser surgery/ressection for conservatory benefits in areas such as larynx has provided good voice and adequate swallowing presservation. Innovative use of intensity modulation radiotherapy (IMRT) offering a better therapeutic index of radiotherapy reducing the risk of xerotosmia (chronic radiation toxicity) (Fanucchi et al, 2006). However, with hearing deficit still signifcant with IMRT due to high toxic doses, tomotherapy now allows tumours to be irradiated with great accuracy, using very high doses but with minimal effect on the neighbouring cells (Nguyen et al, 2011). Immunological innovations have also been proposed to deal with the immunological aspects of the disease such as immune surveillance. Immune therapy, in particular adoptive T Cell therapy, Dendritic cell therapy have shown promise as putative tumour specific therapy with clinical benefits (McKechnie et al, 2004). Finally, Incoporation of molecularly targeted agents have increasingly helped in directing appropriate treatment to locally advanced HNSCC therefore enhancing the effect of the treatment on the tumour. These include Epidermal growth factor inhibitors (EGFRI) and monoclonal antibody cetuximab (Mab Cetuximab) (Bernier, 2008)

8.0Conclusion:

The uncontrolled wide spread of HNSCC associated risk factors around the world particularly in developed countries has led the malignancy to pose a great threat to the population as whole despite the management land marks in place with new treatment procedures under review. Education is still of paramount importance to imbue the general public with the knowledge of the disease, understanding the associated risk factors so as to take precautionary/ preventative measures toprevent the condition.

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Critical Review of the pathogenicity of measles, the symptoms associated with the infection and how to prevent the potentially fatal disease.

Introduction

Measles is a contagious human disease that mainly affects children. The measles virus (MV) that causes this systemic infection is a single stranded ribonucleic acid virus belonging to the genus Morbillivirus in the Paramyxovirus family.(2,3) As transmission is via air droplets, initiation of the infection occurs in the respiratory tract, and spreads to other organs. MV affects the immune system leading to a prolonged state of immune suppression which can result in several complications involving the respiratory tract and the brain e.g. encephalitis.

Immunisation using a live attenuated vaccine is the main preventative of the infection. In 2000, the cases of infection of measles in Europe was rare due to vaccination, however in 2008 there was a total of 7,822 (5) with Switzerland having the highest incidence rate in Europe. (6) Measles are increasing in Ireland, with 320 cases reported within 8 months in 2009. (7) The objective of this assignment it to review the pathogenicity of measles, the symptoms associated with the infection and how to prevent this infectious and potentially fatal disease.

Infection and Spread

Infection is initiated in the respiratory tract. (8) The virus can then spread to the local secondary lymphoid tissues via dendritic cells of the lungs or the alveolar macrophages. (8) From here it can travel to the peripheral blood and spread via epithelial and endothelial cells to multiple organs. Research has suggested that in the later stages of the infection, the virus infects the epithelial cells of the respiratory tract facilitating in the spread of the virus. (9) But how does the virus invade its host?

MV is a non – segmented negative sense strand enveloped RNA virus that encodes 8 proteins: 6 structural proteins and 2 non-structural proteins. (8)

The first 3 structural proteins are combined within the RNA. The (N) nucleoprotein protects the genomic RNA by forming the ribonucleocapsid. The phosphoprotein (P) and large polymerase protein (L) are involved in viral replication. (4, 8)

The non- structural proteins C and V are responsible for the regulation of viral infection by interacting with cellular proteins. (11)

The F and H glycoproteins found on the surface of the virus envelope, are responsible for the initiation of infection to susceptible host cells. These transmembrane proteins allow the virus to fuse with the host cell, penetration of the virus into the host cell and haemolysis. (4) The F protein facilitates the spread of the virus from one cell to the other by inducing cell fusion. (4) Transcription occurs within the cell to create more negative sense RNA for assembly of new budding viruses (see figure 1). (10)

The matrix M protein is a non-glycosylated protein found in the inner lipid bilayer of the envelope. Its function is to connect the ribonucleoprotein complex to the envelope glycoproteins during viral assembly. (8)

The H protein of the virus surface is responsible for receptor binding. CD46 was the first identified receptor for MV and is present on all nucleated cells. (8) It was later discovered that the signalling lymphocyte activation molecule (SLAM) also known as CD150 has also been identified as receptor for MV. (3, 8) In fact the receptor binding of CD46 seems to be limited to attenuated vaccine strains rather than the wild type which seems to have better affinity for the CD 150 receptor. CD150 is expressed on many immune cells including lymphocytes, dendritic cells and macrophages and is a member of the CD2 subset of the Ig superfamily. (3, 8)

The structure of H protein of MV is well documented consisting of a globular head group composed of 6 anti-parallel B sheets. These are stabilised by two intra- monomeric disulphide bonds and partially covered with N-linked carbohydrates. (12) The binding regions for CD 46 and CD 150 (SLAM) are found adjacent to one another. (3)

It has been widely documented that CD150 is the initial receptor targeted by the H protein of the virus but little is known on the receptors involved in the infection of epithelial cells as these cells do not express CD150. (3) Tahara et al have resulted that “MV has the ability to infect both polarised epithelial and immune cells using distinctive receptor – binding sites on the H protein”. (3) His study used a CD150 negative human lung adenocarcinoma cell line (NCI-H358) to infect with the MV. The presence of the H protein was evident using monoclonal antibodies and suggesting that the H protein must have been using a different receptor binding site to infect the cells. (3)

The pathogenesis of MV, initiates an immune response. It triggers a cell-mediated immune response which involves the activation of TH1 and release of interferon ? and interleukin 2 (IL-2). (13) In the later part of the infection an antibody- mediated response provides long term protection against future infections. TH2 lymphocytes are produced as well as IL-4 which favours the induction of a humoral response which is important for long life protection against re-infection. (8, 13) However MV has the ability to dominate the immune system and use it to its advantage. The suppression of the immune system results in secondary bacterial and viral infection which attributes to the number of fatalities associated with Measles infection. Moss et al suggested that there are many mechanisms that develop to immune suppression following a MV infection. (14)

These include:

Lymphocyte Apoptosis
Impaired Lymphoproliferation
Immunomodulatory Cytokines (Increased IL-10 and IL-4)
IL-12 down regulation
Impaired Antigen Presentation of Dendritic cells

One of the clinical manifestations of MV is lymphopenia. This may be due to the reduction of CD4+ and CD8+ T lymphocytes. Increased surface expression of Fas (CD95) during acute measles suggests that unaffected T lymphocytes undergo apoptosis. (14) Abnormalities in the lymphocyte function are found during and after MV infection. The virus inhibits IL-2 dependent T lymphocyte survival and proliferation. This is in response to an impaired protein kinase B activation caused by the H and F proteins of the virus. (14)

In the acute phase of infection a T helper Type 1 (TH1) response is induced which shifts to T helper type 2 (TH2) in the later stage of infection which accounts for viral clearance and development of antibodies respectively. (8) The increased production of cytokines IL-10 and IL-4 in the TH2 response may be another mechanism for viral induced immunosuppression. IL-10 is an immunosuppressive cytokine which down-regulates the synthesis of cytokines and suppresses T cell proliferation and macrophage activation. (15) This prevents macrophage activation and TH 1 response to new infections. (8) As previously mentioned CD 46 is found on many immune cells including monocytes. As a result IL-12 produced by monocytes is downregulated. (16) IL-12 is essential for TH1 immune response. (15) The reduction in production of IL-12 favours TH2 and suppresses TH1 immunity. (17)

Dendritic cells play a critical role in the presentation of antigen to naive T lymphocytes. MV infection promotes maturation of dendritic cells but also alters its function (18) and mediates Fas induced apoptosis.

It is now established that the non-structural protein C and V produced by the P gene plays a role in immunosuppression by interfering with interferon ?/? signalling pathways. (8) These proteins of the MV inhibits phosphorylation of STAT 1 and STAT 2 which are transcription factors involved in the Interferon pathway. (14)

Symptoms

Clinical symptoms associated with measles include a fever and rash but a cough, coryza or conjunctivitis can also be seen. (9) It is after 10-14 days of infection that this characteristic rash is present and seems to be due to the individuals’ immune response to the virus. (8) The rash usually begins on the face and travels down to the extremities and can last for about 5 days before disappearing (4) Two thirds of patients show a white-marked enanthema on the buccal mucosa known as Koplik’s spot. (2) Koplik spots were first identified by Koplik in 1896 and are the pathognomonic of measles. (4, 5) Generally the resolution of the rash and fever begins after 7 to 10 days however the cough may persist for longer. (4) In many cases complication can occur resulting in infections of the respiratory tract and brain.

Pneumonia accompanying measles may be due to the MV or a secondary bacterial infection. (4) 60% of infants infected with measles, can die from pneumonia while older children (10 -14 years) death is associated with acute encephalitis. (4) It seems that viral infection of the CNS is a common feature of measles but only a proportion of patients will present with clinical symptoms.

Mild forms of measles have been observed due to passive immunity to the virus. Infants who have passively acquired antibodies to MV from the mother will present with some of the symptoms but depends on the degree of passive immunity that is achieved. (4) A study in China determined that mothers produced low levels of antibodies due to vaccination rather than natural infection. The outcome is reduced protection to the infant which can result in measles infection before the age of receiving a vaccine. (19)

Atypical measles is associated with patients who received a vaccine using a killed MV rather than live attenuated vaccine and subsequently was exposed to the wild-type measles virus. Patients present with a low or undetectable titre which drastically rises after a few days. (4) As the symptoms may vary to classic measles, it can be misdiagnosed. Atypical measles is more severe than classic measles. Research has shown that this may be due to the fact that the killed vaccine lacks the antigen to stimulate immune response by preventing the virus entering the cells. (4) It has been shown that the killed vaccine does not produces antibodies to the F proteins which facilitate cell entry and spread of the virus.

Immunocompromised patients present with severe measles due to their deficient cellular immunity. Secondary infections are often seen including pneumonia and encephalitis resembling SSPE. Malnourished children especially in the developing world can suffer from severe measles. This may be due to intense exposure due to crowding or the inability to produce a cell-mediated response due to malnutrition. (4)

Measles is regarded as an infection of childhood however adults do get infected and usually develop a severe form which can have complications. During pregnancy, an infected mother is not known to cause co-genital abnormalities to the foetus but may cause abortion or preterm delivery. (4)

Vaccines

The use of vaccines is the main preventative of Measles. The development of the first measles vaccine was in the 1960s. (20) Immunisation began with a inactivated (killed) vaccine, but resulted in short term protection and undeveloped immune system. (20) Immunisation with a live-attenuated vaccine can be administered as a monovaccine or in combination with mumps and rubella (MMR) or mumps, rubella and varicella virus (MMRV). (2) It is derived from a wild type of the virus known as Edmonston and processed through chicken cells. (8) In 1985, the measles virus was first introduced in Ireland, with the combination vaccine (MMR) emerging in 1988. (7) When the vaccine was first introduced in Ireland 9,903 cases of measles were reported. This dropped to 201 cases in 1987. (7) A two dose vaccine is essential for long lasting protection to the virus. (21)

There are occasions when passive immunisation is required using immunoglobulin which include immunocompromised patients such as HIV positive patients. (4)

Successful vaccination against infectious diseases depends on the vaccines ability to induce a protective response. Successful vaccination is dependent on the individuals’ human leukocyte antigen (HLA) haplotype which regulates the immune response. (22) There are two types of HLA proteins. The first, Class I consists of A,B and C alleles. These bind to CD8+ T lymphocytes. (23) Class II DR,DQ and DP alleles attach and present peptides to CD4+ T lymphocytes. (23)

The measles vaccine results in an iatrogenic attenuated measles infection. As mentioned previously, the C46 molecule serves as the receptor for the H protein of MV where it is broken down and presented to the immune system by the HLA system. (22) Studies have shown certain HLA alleles may impact differently on the responsiveness to the measles virus. (22)

For successful herd immunity to measles, most of the population needs to be immunised. However fears of the association of the MMR vaccine and autism have stopped parents from vaccinating their children. There is no scientific evidence to suggest any link with autism. (24)

Research has suggested that Vitamin A supplementation may help prevent Measles infection in infants prior to vaccination. (25)

Subacute Sclerosing Panencephalitis. (SSPE)

One of the persistent secondary infections of MV is subacute sclerosis panencephalitis (SSPE) which causes demyelination of the central nervous system (CNS). (13)

SSPE cannot occur without the presence of a direct measles and is found to be more prevalent in males than in females. (26) Research has shown that the earlier a patient is infected with MV the greater the risk of complications such as SSPE can occur. This is due to an immature immune system. (13)

Conclusion

The MV invades the neurons using the CD46 receptor and using its F protein. (13) There have been studies to suggest that another receptor CD9 aids entry into the cell. Once inside the cell the virus changes the machinery of the cells to avoid an immune response. It undergoes mutations of its own proteins to go unrecognised and reproduces within the neurons. (13) The virus can live as a “parasite” within the neurons for years. Finally it will damage the cell to an extent that apoptosis will occur and the immune system is triggered.

Onset of SSPE is usually 6 years after infection and clinical symptoms present as intellectual deterioration and behaviour abnormalities. Final stages include seizures, focal paralysis and death with akinetic mutism. (13)

There is no cure for this fatal disease only a preventative. Other fears related to the vaccine were that it may cause SSPE however there is no evidence to back this case.

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Free Essays

Can embryonic stem cells be used in the treatment of Parkinson’s disease?

Abstract:

Current treatments of Parkinson’s disease (PD) remain symptomatic, for example Levadopa, and results in a number of negative side effects after a foreseen period of time. However, investigations into using human embryonic stem (ES) cells to generate dopaminergic neurons hold huge potential for future treatments. Results show several patients gain an increased percentage of dopaminergic neural mass in the substantia nigra following transplantations of neural cell grafts into the striatum. This suggests that grafts can work, although other studies show some patients fail to show improvements. There is also the risk of the formation of teratomas and teratocarcinomas in post-operative subjects, due to the self-renewal characteristics of the stem cells. Despite a number of studies proving that using human embryonic stem cells could be a reliable method of treatment, there are still a number of issues unresolved. Since the majority of experiments have taken place on primates, it is unreliable to assume that the same results would occur in human trials. There are also a number of ethical issues such as destroying the ‘potential human life’ of an embryo which, in several cases, is limiting the research and progression of new methods of treatment.

Introduction

Parkinson’s disease is a progressive degenerative disease of the substantia nigra, resulting in the depletion of dopamine in the striatum and the formation of protein bundles known as lewy bodies (1); such depletion of dopamine results in motor symptoms of which patients with PD present with, including resting tremor (2, 3). At present, the most common form of treatment for PD is Levadopa; however, it is only given once symptomatic and is thought that its effectiveness decreases over time (1). Investigations into the treatment of PD involving the use of embryonic stem cells to generate dopaminergic neurons for transplantation into the brain is currently in progress and this review is going to look at the prospects and issues that the use of human embryonic stem cells may bring about. (4).

What are human embryonic stem cells?

Human ES cells are unspecialised and can differentiate into a range of cells via cell division, in this case the most important being dopaminergic neurons (5). Human ES cells are generated from the pre-implantation stage of an embryo, a blastocyst, and can multiply rapidly, generating large numbers of cells (5, 6). This suggests there could be enough to provide sufficient amounts of DA neurons for clinical procedures. ES cells are taken from the eggs that have been fertilised in vitro, provided by consented donors (7, 8).

How are human embryonic stem cells being used to generate dopaminergic neurons?

ES cells are being used to produce tyrosine hydroxylase positive neurons by culturing, expansion and differentiation (fig 1). ES cell colonies are selected individually and grown in agar plates allowing for embryoid bodies to develop. Embryoid bodies are then further cultured in a medium containing Fibroblast Growth Factor-2 (FGF-2) for seven days. A number of cell masses in rosette formations (figure 2b), resembling neural tube structures, were observed within the embryoid bodies (6).

Figure 1: Generating Dopaminergic neurons (12).

Neural precursors showed expression of ‘nestin and musashi’, markers for neural progenitor cells (4): they act as a form of labelling identifying specific cells (9): Without FGF-2, no rosettes of orderly formation grew (6). When spherical neural masses formed after 14 days (figure 2a), it was noted that they could develop and multiply for over 120 days, providing evidence that there would be vast numbers of cells available for treatment (4).14 days is a short period of time tells us how efficient this method of neuron generation is.

Figure 2: A – time in culture. B- ES cell colonies (10).

One study (10) found that the number of tyrosine hydroxylase-positive cells generated by neural masses was very small (5.4% +/- 1.8%) and to increase these figures, looked at the effects of growth factors and how they altered differentiation in culture. When FGF2 and FGF20 were present, percentages of TH+ cells increased by 18.6%; however, neither growth factors alone had such an effect. Once cultured in a differentiation medium, neural masses showed physiological characteristics of neurons providing evidence that differentiation was in progress. (4).

What evidence is there to suggest that human embryonic stem cells may be used as an alternative treatment for Parkinson’s disease?

Several studies (4, 5, 11) quote that human ES cells are able to successfully produce dopaminergic neurons and decrease the symptoms of PD when grafted into the brain. One study (10) experimented on a primate model with an induced form of PD and investigated as to whether the isolated TH+ neurons were able to function as dopaminergic neurons. The neurospheres grown from ES cells were grafted into the putamen of monkeys, only of which started to show signs of PD and whose conditions had deteriorated beyond a period of 12 weeks. After transplantation, the behaviour of the primates was observed and analysed using MRI scanning. 10 weeks following, neurological scores of the primates increased significantly in comparison to the control models. Having a control enables a clearer analysis to take place, and distinguish definite improvements in the primates’ behaviours.

A similar investigation (11) performed bilateral implants on 61 patients into the putamen. When looking at fluorodopa PET scans 12 months post-surgery, 85% of patients presented with neural mass growth and showed physiological improvements. However, one study (9) suggests that the outcome for each individual is not certain to gain the same result, because processes such as apoptosis are unable to be controlled, resulting in cell death within days after transplantation: this presents in scans as a lack of fluorodopa uptake, suggesting a range of cell survival. It is thought that if treated with neurotrophic factors before surgery, it could improve cell survival (11).

Comparing the two studies (10, 11), both results showed promising improvements, emphasising that although one study (10) was on primates, and the second (11) involved humans, both experiments gained a similar positive result. However, this point could be argued as the primate was induced with PD rather than developing the progressive disease naturally.

Analysis of more than one trial (11, 12) has indicated that the response to transplantation could show a positive correlation alongside the patients’ ability to successfully react to L-dopa prior to the operation, as well as the patients’ stage of disease. One study (12) presented that if a patient scored lower that 50 on the unified Parkinson’s scale before surgery, then they were more likely to gain a positive result from the transplant. Some may say that for the treatment to be appreciated, it shouldn’t matter what stage the patient is at when receiving the transplant, and that it should work at all stages of the disease, although as proven with diseases such as cancer, this is not always possible.

As well as increased F-dopa uptake, a studies on animals (13, 14) observed rotational behaviour in response to amphetamine before and after surgery. Results showed a decrease in the scores of the animals given the graft, whilst sham controls showed no improvement (figure 3). One study (13) was repeated on 4 occasions across a 9 week period and continued to show gradual reduction. This provides evidence that the graft was beginning to improve dopaminergic neuron function, as motor functions were showing significant improvements (14).

Figure 3: Rotational behaviour scores (13)

Another study (12) says that neurons generated from the cells of early aborted embryos are able to survive when transplanted into the striatum and recover the loss of function by 10-40%, by restoring dopamine production in the grafted area (15). However, such results may be unreliable in respect to human transplants as these studies were performed on rats and monkeys, of which the disease was induced by creating selective lesions. Such lesions are, therefore, in a different condition compared to natural lesions found in the brain of a patient with progressive PD (9).

Transplants are thought to have decreased the occurrence of dyskinesias, a side-effect of levodopa; however, this has mostly only been proven in rats and monkeys. In addition, a number of patients have been able to stop using levodopa completely, although this is not a regular occurrence. On the contrary, a number of subjects have been noted having developed off dyskinesias: 7-15% of grafted patients (5). It is thought that this is down to the fact that the neurons are unable to function properly; this could be due to the overproduction of dopamine in the striatum (12). If there are consequences after transplantation, of the same severity as previous to the transplant, is it worth performing the operation?

How are the generated neurons transplanted into the patientWhat are the issues with this?

Grafts are injected into the brain whilst under anesthesia (16) and, as with all surgery, poses risks such as haemorrhage and infection (15). To minimise this, the number of needle passes is kept to a minimum. This was demonstrated in more than one case (9, 11, 15) where the needles were passed through the front of the head, through to the putamen bilaterally using a total of 4 needles (figure 4). In one study (16), 8 needle passes were used, however, this had no detriment to the outcome of the transplants, both achieving regeneration. ES cells themselves also pose risks. With characteristics such as pluripotency and self-renewal, stem cells have the potential to form teritomas and teratocarcinomas which, at present, is one of the greatest risks; without knowing that they won’t form, transplatation of human ES cells will cease to be promising (17).

Figure 4: MRI and PET scans showing F-DOPA uptake and needle passes (8).

In order for this method to be successful, such characteristics of the cells need to be able to be controlled, and by doing so, will reduce the likelihood of teramtomas forming. Nonetheless, human ES cells maintain a normal karyotype and, therefore, these growths are not thought to be of the malignant variety (5). Despite this, there is evidence to suggest that teratomas formed from the transplantation of early or unspecified neurons into the brain, can lead to incomplete motor benefit in models of PD (18).

In the majority of studies, patients were given immunosuppressive therapy before surgery to prevent rejection. The drug Cyclosporin was given, however, the course of the treatment varied, fluctuating between 2 days to 2 weeks (8, 11, 19). In such cases, when the immunosuppressive medication was withdrawn post-operatively, there was no evidence of reduction in f-dopa uptake, suggesting that the graft was functioning properly (19). One study (9) claims that immunosuppressive treatment is not needed when the graft is kept within the same species.

What ethical issues are there with using human embryonic stem cells?

One question that will continue to be brought up in regards to embryos is ‘at what stage is the embryo a human life?’ One book (20)suggests that for research on an embryo to commence, informed consent must be given as many people believe that the blastocyst has the potential to be a human being. However, because an embryo is incompetent of doing so, then the research cannot take place and, if it did, then it is thought that it would be restricting the embryos right or potential to life. Despite this, the use of stem cells derived from blastocysts continues to take place (20).Opinions vary and many of those who object to the use of embryos are subject to religious views: it is not necessarily a personal opinion but a matter of principle as to who has the right to determine life or death.

One way of presenting the idea of using ES cells to those ethically opposed is by carrying out a benefit to risk ratio, weighing up the pros and cons of the situation. One argument (21) emphasises potential relief of symptoms, and the withdrawal of pharmacological treatment. It could not only benefit the subject, but also influence those affected indirectly by PD. Opposing to this are the risks of tumour formations and infection both during and after surgery, along with rejection by the immune system.

With ethical issues in mind, Parthenogenesis has provided an alternative way of deriving pluripotent stem cells without damaging embryos, preventing the destruction of potential life. Asexual reproduction of sex cells could be the route to generating vast amounts of pluripotent stem cells appropriate for transplantation, without the ethical issues that we face today (18).

Discussion:

Looking at the evidence provided, it is viable to conclude that the use of human ES cells to produce dopaminergic neurons for transplantation into the brain has potential for future treatments. However, at present, studies are unable to provide valid evidence that this alternative treatment is guaranteed to work on a world-wide basis, as there is yet to be a steady correlation of improved brain function post-operative. Alongside this, there will continue to be a number of ethical arguments against the idea with respect to using human embryos as the source of stem cells, although, as discussed previously, other methods of generating stem cells such as parthenogenesis could be the answer to this. A greater knowledge of how the cells are differentiating and having the ability to gain control of this would provide a much better prospect for the future pioneers of embryonic dopamine cell transplantation. With greater research and more promising results, the use of human ES cells to generate dopaminergic neurons could provide an effective method of treatment in the near future, which could lead to the successful restoration of normal brain function.

References:

(1) Schapira, A.V.H., 1991. Parkinson’s Disease. Science, Medicine and the future, 318, pp.311-314

(2) Chinta, S.J., Andersen, J.K., 2005. Cell focus in Dopaminergic Neurons. The International Journal of Biochemistry & Cell Biology, 37, pp. 942–946

(3) Zigmond, M.J., Burke, R.E., Pathophysiology of Parkinson’s disease. Neurpharmacology: the fifth generation of progress, 123, pp.1782

(4) Soo Cho, M., Lee, Y.E., Kim, J.Y., Chung, S., Cho, Y.H., Kim, D.S., Kang, S.M., Lee, H., Kim, M.H., Kim, J.H., Leem, J.W., Oh, S.K., Choi, Y.M., Hwang, D.Y., Chang, J.W., Kim, D.W., 2008. High Efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells. PNAS, 105, pp3392-3397

(5) Wainwright, S.P., 2005. Can stem cells cure Parkinson’s disaeaseEmbryonic steps toward a regenerative brain medicine. British Journal of Neuroscience nursing, 1(3), pp.110-115

(6) Zhang, S.C., Wernig, M., Duncan, I.D., Brustle, O., Thomson, J.A., 2001. In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nature, 19

(8) Mendez, I., Sanchez-Pernaute, R., Cooper, O., Vinuela, A., Ferrari, D., Bjorklund, L., Dagher, A., Isacson, O., 2005. Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson’s disease. Brain, 128, pp. 1498-1510

(9) Bjorklund, A,. Dunnett, S.B., Brundin, P., Stoessl, A.J., Freed, C.R., Breeze, R.E., Levivier, M., Peschanski, M., Studer, L., Barker, R., 2003. Neural transplantation for the treatment of Parkinson’s disease. The Lancet Neurology, 2, pp.437-445

(10) Takagi, Y., Takahashi, J., Saiki, H., Morizane, A., Hayashi, T., Kishi, Y., Fukuda, H., Okamoto, Y., Koyanagi, M., Ideguchi, M., Hayshi, H., Imazoto, T., Kawasaka, H., Suemori, H., Omachi, S., Iida, H., Itoh, N., Nakatsuji, N., Sasai, Y., Hashimoto, N., 2005. Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model. The Journal of Clinical Investigation, 115(1), pp.102-109

(11) Freed, C.R., Leehey, M.A., Zawada, M., Bjugstad, K., Thompson, L., Breeze, R.E., 2003. Do patients with Parkinson’s disease benefit from embryonic dopamine cell transplantationJ Neurol, 3, pp.44-46

(12) Isacson, O., 2003. The production and use of cells as therapeutic agents in neurodegenerative disease. The Lancet Neurology, 2, pp.417-424

(13) Bjorklund, L.M., Sanchez-Pernaute, R,. Chung, S., Anderson, T., Yin Ching Chen, I., McNaught, K.S.P, Brownell, A.L., Jenkins, B.G., Wahlestedt, C., Kim, K.S., Isacson, O., 2002. Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. PNAS, 99 (4), pp.2344-2349

(14) Kim, J.H., Auerbach, J.M., Rodriguez-Gomez, J.A., Velasco, I., Gavin, D., Lumelsky, N., Lee, S.H., Nguyen, J., Sanchez-Pernaute, R., Bankiewicz, K., McKay, R., 2002. Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature, 418, pp.50-56

(15) Freed, C.R., Greene, P.E., Breeze, R.E, Tsai, W.Y., DuMouchel, W., Kao, R., Dillon, S., Winfield, H., Culver, S., Trojanowski, J.Q., Eidelberg, D., Fahn, S., 2001. Transplantation of Embryonic dopamine neurons for severe Parkinson’s disease. The New England Journal of Medicine, 344 (10), pp.710-719

(16) Olanow, C.W., Goetz, C.G., Kordower, J.H., Stoessl, A.J., Sossi, V., Brin, M.F., Shannon, K.M., Nauert, M., Perl, D.P., Godbold, J., Freeman, T.B., 2003. Double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol, 54, pp.403-414

(17) Wu, D.C., Boyd, A.S., Wood, K.J., 2007. Embryonic stem cell transplantation: potential applicability in cell replacement therapy and regenerative medicine. Frontiers in Bioscience, 12, pp.4525-4535

(18) Sanchez-Pernaute, R., Lee, H., Patterson, M., Reske-Nielsen, C., Toshizaki, T., Sonntag, K.C., Studer, L., Isacson, O.,2008. Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson’s disease. Brain, 131, pp.2127-2139

(19) Piccini, P., Pavese, N., Hagell, P., Remier, J., Bjorklund, A., Oertel, W.H., Quinn, N.P., Brooks, D.J., Lindvall, O., 2005. Factors affecting the clinical outcome after neural transplantation in Parkinson’s disease. Brain, 128, pp.2977-2986

(20) Cusine, D.J., 1991. Experimentation: some legal aspects. Experiments on Embryos, (editors Anthony, D. Harris, J) pp.120. Routledge: London

(21) Master, Z., McLeod, M., Mendez, I,. 2007. Benefits, risks and ethical considerations in translation of stem cell research to clinical applications in Parkinson’s disease. Journal of Medical Ethics, 33, pp.169-173

Web References:

(7) National Institute of Health. Stem Cell Basics. [online] Available at: [Accessed 9th March 2011].

Figure References:

Title page: Available at: [Accessed 21st March 2011]

Figure 1 (12) – Isacson, O., 2003. The production and use of cells as therapeutic agents in neurodegenerative disease. The Lancet Neurology, 2, pp.417-424

Figure 2 (10) – Takagi, Y., Takahashi, J., Saiki, H., Morizane, A., Hayashi, T., Kishi, Y., Fukuda, H., Okamoto, Y., Koyanagi, M., Ideguchi, M., Hayshi, H., Imazoto, T., Kawasaka, H., Suemori, H., Omachi, S., Iida, H., Itoh, N., Nakatsuji, N., Sasai, Y., Hashimoto, N., 2005. Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model. The Journal of Clinical Investigation, 115(1), pp.102-109

Figure 3 (13) – Bjorklund, L.M., Sanchez-Pernaute, R,. Chung, S., Anderson, T., Yin Ching Chen, I., McNaught, K.S.P, Brownell, A.L., Jenkins, B.G., Wahlestedt, C., Kim, K.S., Isacson, O., 2002. Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. PNAS, 99 (4), pp.2344-2349

Figure 4 (8) – Mendez, I., Sanchez-Pernaute, R., Cooper, O., Vinuela, A., Ferrari, D., Bjorklund, L., Dagher, A., Isacson, O., 2005. Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson’s disease. Brain, 128, pp. 1498-1510

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Riluzole in the treatment of Lou Gehrig’s disease

Introduction

Lou Gehrig’s disease is often referred to as Amyotrophic lateral sclerosis (ALS), this is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Motor neurons come from the brain to the spinal cord and from the spinal cord to the muscles throughout the entire body. The progressive degeneration of the motor neurons in ALS would eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is also lost. With voluntary muscle action progressively affected, for this reason patients in the later stages of the disease may become totally paralyzed (Choi, 1988).

ALS is led to mean no muscle nourishment. When a muscle has no nourishment, it atrophies or wastes away hence the name. In addition to this, lateral shows the areas in a person’s spinal cord where part of the nerve cells that signal and control the muscles are located. As this area degenerates, it leads to scarring or hardening (sclerosis) in this particular region.

As motor neurons degenerate, this obviously means they can no longer send impulses to the muscle fibers that otherwise normally result in muscle movement. Early symptoms of ALS often include increasing muscle weakness, especially involving the arms and legs, speech, swallowing or breathing. When muscles no longer receive the messages from the motor neurons that they require to function, the muscles begin to atrophy (become smaller). Limbs begin to look thinner as muscle tissue atrophies (Choi, 1988).

Neurodegeneration is used mainly for diseases that are characterised by progressive loss of structure and function of neurons. There are many neurodegenerative diseases including amyotrophic lateral sclerosis that occurs as a result of neurodegenerative processes in selective areas. Several molecular studies have been designed both in animal models and in humans to determine the physiopathology of the disease in order to develop new approaches for neurodegeneration. ALS is a neurological disease of unknown origin which is characterised by a selective degeneration and death of upper and lower motor neurons this progresses to paralysis and death over a period of time.

ALS diagnosis is based on the El Escorial criteria carried out on mainly clinical and electrophysiological findings in four body regions. Also around 95% of ALS patients are sporadic whereas 5% are familial. In this particular group approximately 15% are caused by mutations in the SOD one gene that codes for the CuZn superoxide dismutase-1 (Bensimon, 1994). This is an enzyme that catalyzes the dismutation of superoxide to molecular oxygen and hydrogen peroxide. The symptoms and pathology of familial ALS patients with SOD1 mutations resemble those of patients with sporadic ALS. This suggests there are common mechanisms of neuron degeneration in both forms of the diseases. Several potential mechanisms of motor neuron degeneration in ALS have been projected. These include the involvement of environmental and genetic factors, autoimmune phenoma, increased oxidative stress, glutamate toxicity, viral infections, mitochondrial dysfunction and cytoskeletal abnormalities. This means that each mechanism involvedin the pathogenesis of ALS may represent a possible thjerapeutic approach to counteract neurodegeneration.

Glutamate is the primary excitatory neuro transmitter in the central nervous system which acts at both iono-tropic and metabotropic receptors, the primary ionotropic receptor classes being N-methyl-D-aspartic acid (NMDA) and (AMPA)/kainite. Extracellular glutamate levels are regulated by transporters, they have different transporter classes on neurons and on astrocytes, however most of the glutamate uptake appears to be mediated astrocytes. Excessive glutamate exposure is toxic to neurons which is most likely that is results from glutamate triggeredCa2+ entering the neurons. Also inhibitors of glutamate uptake can cause selective motor neuron damage in organotypic slice and in dissociated spinal cord culture models. This suggests that the increased extracellular glutamate concentration could add to motor neuron damage in ALS. Furthermore, observations of deficient glutamate transport capacity in affected regions of spinal cord and motor cortex show a likely reason for the rises in extracellular glutamate concentration.

The only drug proven to slow the process of human ALS is the anti-excitotoxic compound Riluzole, which is an anti-convulsant and a neuro-protective agent and specifically blocks sodium channels in their inactivated states. This inhibits the release of glutamate by inactivating voltage dependent Na+ channels that are on the glutamatergic nerve terminals as well as activating a G-protein dependant signal transduction process, this slows down disease progression and in turn increases the patient’s survival rate. In addition to this Riluzole can also block some of the postsynaptic effects of glutamate, this is done by non-competitive inhibition at NMDA and AMPA receptors. For this reason a non competitive modulator of AMPA glutamate receptors has been used in clinical trials in ALS patients (Barbeito, 1996).

Several studies showed that also the clearance of glutamate from neuromuscular synapases is slowed down in patients with ALS due to the loss of a glutamate transporter which is the excitatory amino acid transporter 2, this is of huge importance for synaptic glutamate re-uptake. A loss of high-affinity glutamate transport transport has been identified in specific brain regions and spinal cord of patients with ALS (Bensimon, 1996). From the above these results suggest that the defect in glutamate transport could be responsible for high elevations in extracellular glutamate.

These results have supported the use of cephalosporins in ALS because of their antiexcitatory properties, this is done by increasing EAAT2 promoter activity. Also for human studiesthird generation ceftriaxone has been selected because of its superior CNS penetration and long half life. From this ceftriaxone observed a considerable improvement of antioxidant oxidative stress status in ALS patients after treatment.

Riluzole treatment has been tested in trials which examine tracheostomy free survival rate, this included 974 riluzole treated patients. In respect to this the methodological quality of the experiment was acceptable and the trails were easily comparable. The results show that riluzole 100mg per day would provide benefits to the homogenous groups of patients with no evidence of heterogeneity. Also there was a 9% gain in the probability of surviving one year. Furthermore there was a small beneficial effect on both bulbar and limb functions but had no effect on muscle strength. Another significant effect which is represented in these results are a threefold increase in serum alanine transferase, this was more frequent in riluzole treated patients than the controls in the experiment (Wahl, 1997).

In conclusion Riluzole 100mg daily is fairly safe and most likely prolongs median surbival by around two to three months in patients with amyotrophic lacteral sclerosis. However more research needs to be done to treat Lou Gehrigs disease such as different therapeutic strategies and oxidative stress in ALS can be looked at in further depths.

References
Barbeito, L. Estevez, A. and Stutzmann, J. Peluffo, H. (1996) Riluzole promotes motoneuron survival by stimulating neurotrophic activity produced by spinal astrocyte monolayers, J. Neurotrauma, 13: 629.
Bensimon, G., Lacomblez, L., Meininger, V. (1994). A controlled trial of riluzole in amyotrophic lateral. sclerosis, New Engl. J. Med., 330 : 585–591.
Choi, D. (1988). Glutamate neurotoxicity and diseases to the nervous system. Neuron, 1: 523–634.
Bensimon, G. Guillet, P. Lacomblez, L. Leigh, P. Meininger,V. (1996). Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Lancet, 347: 1425–1431.
Mary, V. Wahl, F. Stutzmann, M. (1995). Effect of riluzole on quinolinate-induced neuronal damage in rats: comparison with blockers of glutamatergic neurotransmission. Neurosci Lett. 201: 92–96.
Wahl, F. Renou, E. Stutzmann, J. (1997). Riluzole reduces brain lesions and improves neurological function in rats after a traumatic brain injury. Brain Research, 756: 247–255.

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The role of ApoE and its isoforms in Alzheimer’s disease

Introduction

Research into the genetic causes of Alzheimer’s disease have progressed considerably and currently at least three different genes are known to be linked with AD pathogenesis. Of these the apolipoprotein gene E (APOE), an amino acid glycoprotein, is one of the main focus of research over the last decade or so and significant associations between one particular isoform of the gene and the onset of AD have been reported. This isomer, referred to as the ApoE 4 allele, has been implicated in AD pathogenesis while other forms of the gene the ApoE 2 and the ApoE 3 have been reported to have a protective effect against the onset of AD. Though research has confirmed this variable effect of the different forms of the ApoE gene, there is still a lack of concrete evidence as to the exact pathway and the mechanism by which ApoE 4 contributes to neurodegeneration in AD patients. A brief review of related research would provide us more insight into the various pathological actions of ApoE 4 and how these multiple factors could lead to a gradual cognitive decline which is symptomatic in Alzheimer’s patients.

The ApoE gene (Physiological Functions)

ApoE is an amino acid glycoprotein that is found mainly in the liver and the brain. In the brain, ApoE is predominantly secreted by the astrocytes. Two other forms of apolipoproteins namely ApoA-1 and ApoJ are also found in the brain. In vitro studies of these two genes have so far suggested that both of them exhibit a neuroprotective effect. Both these proteins bind to A? and therefore are thought to reduce A? aggregation in the brain which is a known marker of AD. However, in vivo studies have not replicated such results and so the protective roles of ApoA-1 and ApoJ are not yet clear. The ApoE supports cholesterol equilibrium by serving as a ligand during endocytosis of lipoprotein particles by LDL receptors. Research is divided in the opinion that the cholesterol released from ApoE mediated endocytosis process is actually used for improving the synaptic connections or the synaptic plasticity. Mice based in vivo studies have not attested to this synaptogenesis. (Kim et.al, 2009)

The ApoE isomers

Three single nucleotide polymorphisms of the ApoE gene are commonly identified in humans. These are the apoE2 (cys112, cys158), apoE3 (cys112, arg158), and apoE4 (arg112, arg158) respectively. (Kim et.al, 2009) The structural and functional aspects of the three isomers of ApoE are totally altered though they differ by only one or two amino acid positions. Studies have reported strong immune-reactivity of the human apoE4 gene on amyloid plagues and the apoE4 isomer has been associated with having a strongest risk factor for AD. Some studies such as (Bertram et al., 2007) and (Bertram et al., 2009) have attested to this role of the apoE4 isomer in AD. Bertram et al., 2009 for instance reported that people with a single copy of the apoE4 gene had a three fold increase in risk for AD, while the risk was 12 fold among those with a dual copy of the ApoE4 gene. The results from studies also suggest the possible role of some environmental factors as research based on some ethnic groups have revealed that the ApoE 4 gene does not have a significant effect on AD.

ApoE & A? Aggregation (Fibrillogenesis)

Several research studies have focused upon the potential role of ApoE 4 in causing A? aggregation and neuronal degeneration. This direct interaction between the ApoE 4 with beta amyloid is attributed in the pathogenesis of the disease. Therefore it was hypothesized that increased levels of ApoE 4 in the brain corresponded to increased formation and thickness of amyloid plaques. The findings from one comprehensive study by Tiraboschi et.al (2004) validated this hypothesis. The researchers in this study confirmed increased plaque density corresponding to increased levels of ApoE 4.

This positive association was again confirmed by a more recent study by Reiman et.al (2009). The researchers of this study used an amyloid detecting agent such as Pittsburgh compound B (PIB) along with positron emission tomography to detect the levels of fibrillar A? in the subjects. The researchers then correlated this information among individuals with varied genetic risks. The results from the study clearly revealed that ApoE 4 homozygotes had the highest risk (91%) for developing AD while ApoE 4 heterozygotes had a moderate risk of 47% and finally ApoE 4 non carriers had only 20% risk of having AD. Furthermore, the mean age of onset of AD was also vastly different with ApoE 4 homozygotes at 64, heterozygotes at 76 and 84 years of age among non carriers. This longitudinal study clearly provides positive evidence connecting the ApoE 4 gene with a high risk for AD. Thus there is enough evidence that ApoE 4 gene may aid in ?brillogenesis and consequent cognitive decline. (Reiman et.al 2009).

A? Clearance by ApoE

Some studies have shown that ApoE by binding with soluble A? promotes the cellular uptake and ingestion of the ApoE –A? complexby endocytosis. However, isomer specific results for this ApoE facilitated cellular uptake of A? are still awaited. Research has also focused on the possible clearance of A? from the brain via the blood brain barrier. However, there is growing evidence that ApoE 4 might actually hinder or reduce this clearance of A?. Deane et.al (2008), a study based on mice reported that the clearance rate of ApoE 4 –A? complex is much lower than that for the ApoE2 and ApoE 3 complexes. Other recent studies such as Bell et.al (2007) and Ito et.al (2007) that focused on studying the A? clearance in humans found that the clearance rate along the Blood Brain Barrier (BBB) was significantly lower for the ApoE 4 –A? complex compared to that of simple A? peptides. These studies offer enough evidence that ApoE 4 might actually increase the fibrillogenesis by directly affecting the A? metabolism in the brain. By reducing the clearance rate and promoting aggregation ApoE 4 gene definitely poses an increased risk factor for AD.

ApoE and Neuronal Inflammation

Several studies have reported that ApoE has marked anti inflammatory properties which explain the surge in their production in the aftermath of an injury. These studies hypothesize that ApoE is needed for maintaining the cholesterol homeostasis, and in particular for increasing the availability of cholesterol for neuronal repair and improving the synaptic plasticity subsequent to brain injury. (Slezak & Pfriege, 2003 ). However studies have also reported differences in neurite growth and synaptic plasticity post neuronal insult in animal studies based on the genotype. One transgenic mice study found that neuronal growth and synaptogenesis were markedly lower among ApoE 4 transgenic mice compared to ApoE3 transgenic mice. (White et.al, 2001) An extensive review of the neuroprotective effects of the various ApoE isomers by (Cambon et al, 2000) clearly showed differential effects between the isomers. Most of the studies reported that ApoE3 promoted synaptic plasticity and neurite growth. However similar positive results were not witnessed in the case of ApoE 4 alleles with some studies even reporting the negative effects of ApoE 4 on synaptic plasticity and neuronal growth. Colton et.al (2004) found that the anti-inflammatory effects vary drastically between the ApoE isomers. The researchers studied this variability in anti-inflammatory response triggered by the ApoE 3 and ApoE4 isomers by using in vivo experiment conducted on ApoE knockin mice. By studying Lipopolysaccharide (LPS) mediated inflammatory responses the researchers observed the differences between the isomers. The inflammatory response was much greater in the ApoE 4 knockin mice when compared to the ApoE3 Knockin mice. These studies suggest that the anti inflammatory response maybe less active in ApoE 4 and this might lead to neuronal damage as witnessed in AD patients.(Kim et.al, 2009)

Conclusion

The review of studies has revealed that the ApoE isomers have differential effects on the A? metabolism in the brain. While the ApoE 2 and ApoE 3 isomers have been reported for their protective effects the ApoE 4 allele clearly seems to contribute to the AD pathogenesis. Results from recent fibrillar PET imaging studies suggest a clear positive correlation between the ApoE 4 allele and the density of amyloid plaque formation. It is clear that by slowing down clearance of A? as well as contributing to its aggregation in the brain, the ApoE 4 allele increases the susceptibility of a person for AD. It is also possible that the ApoE 4 also lowers the protective function by increasing the neuronal inflammatory response and by hindering neurite growth. More studies are necessary to understand the complex relationship between ApoE and A? and the levels of different isomers of ApoE and their corresponding impact on Neuroinflammation and neurotoxicity, etc.

Bibliography

Jungsu Kim, Jacob M. Basak, & David M. Holtzman, (Aug 13th 2009), The Role of Apolipoprotein E in Alzheimer’s disease, Neuron 63.
Bertram, L., McQueen, M.B., Mullin, K., Blacker, D., and Tanzi, R.E. (2007) Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat. Genet. 39, 17–23.
Bertram, L., McQueen, M.B., Mullin, K., Blacker, D., and Tanzi, R.E. (2009). The AlzGene Database Alzheimer Research Forum available at,
Eric M. Reiman, Kewei Chen,&Xiaofen Liu et.al (Apr 2009), Fibrillar amyloid-? burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease, Proc Natl Acad Sci U S A. ; 106(16): 6820–6825.
Bell, R.D., Sagare, A.P., Friedman, & A.E., Bedi et.al (2007). Transport pathways for clearance of human Alzheimer’s amyloid beta-peptide and apolipoproteins E and J in the mouse central nervous system. J. Cereb. Blood Flow Metab. 27, 909–918.
Ito, S., Ohtsuki, S., Kamiie, J., Nezu, Y., and Terasaki, T. (2007). Cerebral clearance of human amyloid-beta peptide (1-40) across the blood-brain barrier is reduced by self-aggregation and formation of low-density lipoprotein receptor-related protein-1 ligand complexes. J. Neurochem. 103, 2482–2490

Part 2

Fibrillar amyloid-? burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease (Reiman et.al 2009)

This research study by Reiman et.al (2009) hypothesized that fibrillar amyloid accumulation is an early development in the onset of Alzheimer’s disease. The researchers further hypothesized that the fibrillar amyloid accumulation precedes any recognizable symptoms of cognitive decline. Amyloid plaques are a distinct feature of AD as observed from post mortem studies. Given the hypothesis that fibrillar A? accumulation is observed even in healthy, non symptomatic adults, the researchers intended to study the effect of fibrillar A? burden as a predictor of future onset of AD on adults with normal cognitive function using Ante mortem brain imaging studies.

For this study, the researchers used Pittsburgh Compound B (PiB), a radio ligand that binds only with the fibrillar A? species. Earlier studies have also used this PIB for imaging studies of live human brain to observe the formation of fibrillar A? in healthy adults. This study by the authors is aimed to extend the previous studies by providing a genetic risk analysis and to understand the predisposition to AD based on an individuals APOE genotype. The APOE genotypes were identified by using blood sample analysis. The researchers used fluorodeoxyglucose PET, volumetric MRI and neuropsychological tests. Fibrillar imaging was done using 3 dimensional HR+ scanner. The subjects of this study were all cognitively normal and late middle aged people representing a mixture of APOE genotypes. This was a longitudinal study and the subjects were assessed every 2 years.

The researchers observed that cerebral glucose metabolism levels of those subjects carrying dual copy of the ApoE 4 (homozygotes) was significantly lower than that of the heterozygotes and the non carriers. With the PiB Pet images the researchers compared and correlated the fibrillar burden with the genetic risk to understand the predisposition for AD between the various isomers. The average Pittsburgh(PiB) distribution volume rations(DVR), which is a measure of the fibrillar A? accumulation, was on increase in all the three different groups in the 2 years period. One of the homozygote subjects developed mild amnesia and her DVR was close to that of an AD patient. Overall of all the 28 subjects (8 homozygotes, 8 heterozygotes and 12 non carriers), the ROI measurements pertaining to the different brain regions such as temporal, parietal, posterior cingulate-precuneus, basal ganglia, etc, was the highest among the homozygotes.

The researchers used statistical analysis and found that the homozygotes had considerably higher ROI values when compared to the non carriers (P < .05) while the difference between the heterozygotes and the non carriers was not significant (.05 < P < .11). When correlated the APOE4 and Fibrillar A? burden was found to be significant among both homozygotes and heterozygotes compared with the non carriers. The study authors successfully found that even in cognitively normal individuals there is a positive correlation between ApoE 4 and fibrillar A?. The results from the study suggest that the ApoE 4 is clearly associated with increased A? aggregation and decreased A? clearance. The following PET map clearly indicates the various regions of the brain that are affected by A? accumulation.

Group A represents the homozygotes while group B and C represent the heterozygotes and non carriers respectively.

Longitudinal studies are very effective in following the growth of fibrillar A? accumulation as they provide a clear pattern of disease progression even in the asymptomatic stage. People who are in late middle age who are at risk for AD would greatly benefit from a prophylactic intervention based on the brain mapping study and their ApoE genotype. This study clearly contributes to our understanding that the ApoE 4 is directly involved in the A? interaction and the formation of Amyloid Plaques. By considering live brain images for the study the authors were able to clearly confirm the association between the ApoE 4 and A? fibrillar density and predict the increased susceptibility of people with that genotype.

This study has large implications for the treatment of AD. By proving that A? fibrillar formation precedes a perceivable cognitive decline, this study recommends early interventions particularly for people with ApoE 4 genotype, as the current A? modifying treatments would be more effective before extensive A? accumulation has occurred. The researchers advocate the use of brain imaging studies combined with genotype based risk assessment as a potentially powerful tool in preventive therapy for people who are at a genetically high risk for AD. One of the drawbacks of the study is the very small study sample. A large cohort based longitudinal study would have provided more conclusive confirmation of the study results.

Bibliography

Eric M. Reiman, Kewei Chen,&Xiaofen Liu et.al (Apr 2009), Fibrillar amyloid-? burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease, Proc Natl Acad Sci U S A. ; 106(16): 6820–6825.

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What does the study of brain injury and disease tell us about normal brain functioning?

Abstract

Although the study of injured and damaged brains dates back to the 19th century, the field of cognitive neuropsychology emerged in the 1960’s, and sought to explain the make up and architecture of normal and intact brains by exploring how the brain breaks down after illness or injury. This paper charts the history of cognitive architecture from inception to modernity, discussing techniques, strengths, shortcomings and modern applications. Although not without issue, it is suggested that imaging techniques such as fMRI will not only continue to expand our knowledge of normal brain functioning, but may have explanatory power in the field of mental disorder,

Introduction

Cognitive psychology is the scientific study of mental functions, and believes such functioning, or cognition, can be explored using the scientific method. It states that all individual components of mental functioning can be identified and understood. Such components are referred to as modules, and therefore any theory regarding the domains of cognition will be a theory of the modules of the system that create the cognitive performance, and a theory of the cognitive architecture of the system. One way in which brain modules and functional architecture can be understood is by studying the way in which the brain breaks down after illness or injury; the science of cognitive neuropsychology.

Main Body

Cognitive neuropsychology emerged as a distinct approach during the 1960’s, but has roots as far back as the 19th century. Pierre Paul Broca’s 1891 post-mortem study of aphasic patient ‘Tan’ who could not produce speech, despite understanding and following directions revealed damage to an area of the frontal lobe (now dubbed ‘Broca’s area’), and provided the first indication that areas of the brain may be specialised for language production.

Commonly cited as the first in the field of cognitive neuropsychology, the series of case studies of patient HM played a crucial role in identifying areas of the brain specific to memory functions (Scoville & Milner, 1957). In 1953, due to severe and untreatable epilepsy, HM had his medial temporal lobes surgically removed. Although successful in treating HM’s epilepsy, he was left with profound yet selective amnesia; specifically anterograde amnesia. Although his working and procedural memory remained intact, he could not commit new information to his long term memory. As the loss of brain matter was surgical, and the damaged areas could be precisely identified, the case of HM revolutionised the study of human memory. In the first, the loss of HM’s medial temporal lobes could be held responsible for his lack of memory, but more crucially, his ability to perform tasks that required recall from short-term and procedural memory, but inability to recall from the long-term memory suggested that different memory processes were mediated by different areas of the brain.

However, these early descriptions of neuropsychological syndromes depended solely on the presentation of neuropsychological deficits and post-mortem analysis. These shortcomings led to the development of the lesion method, the study of patients with lesions to the brain. This involved correlating knowledge of precise damage to the brain with knowledge of specific cognitive impairments.

Although lesion studies allowed for the pinpointing of trauma within the brain (unlike the study of already brain-damaged patients), a major problem was that scientists were unable to confidently claim that lesioned brains mediated cognitive processes identically to intact brains. These led modern theorists came to question the utility of using only damaged brains to explore psychological processes.

Contemporary neuropsychology drew on modern neuroimaging of intact brains to allow considerable developments in the understanding of brain-behaviour relationships. Advancements in techniques such as Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI) “led to an explosion in their application in the field of experimental psychology in general and cognitive psychology” (Page 2006; p.429), and the use of fMRI techniques has increased steadily since the outset of their routine use in the early 1990’s. This is for a number of reasons; firstly advances in fMRI techniques have improved their precision, thus the data they produce has become increasingly reliable whilst remaining non-invasive and safer than traditional methods of neuroimaging such as PET (Aue, Lavelle & Cacioppo, 2009). Secondly, they are of particular benefit in studies including human participants, as they allow for the investigation of psychological operations without relying upon verbal reports. This benefit is two-fold; fMRI add of objectivity, whereby verbal reports may be distorted, plus they allow for the investigation of operations to which participants have no verbal access (Aue, Lavelle & Cacioppo, 2009).

Critics of this approach point out that studies relying on imaging techniques are particularly susceptible to inferential errors. Brain activation in one area is inferred as indexing a particular psychological state without considering the antecedent circumstances to that particular activation (Aue, Lavelle & Cacioppo, 2009). Furthermore, some theorists claim that such approaches do not advance psychological theory. As Kilstrom (2006) stated:

“There does not appear to be any instance where neuroscientific findings have constrained social-psychological theory…To the contrary, it appears that precisely the reverse is true: psychological theory constrains the interpretation of neuropsychological and neuroscientific data.” (Kilstrom 2006: p.16)

Despite this, modern imaging techniques have remained the measure of choice in psychological studies of brain activity. Research has seemingly gone full circle to take exciting new directions in the field of cognitive neuropsychiatry. Although in its infancy, researchers have begun to re-apply imaging techniques to the study of disordered individuals. This has led to comprehension of previously misunderstood disorders of face recognition such as prosopagnosia and Capgras Syndrome, and better understanding of brain activity in individuals suffering from a range of mental health problems.

Conclusion

Much can be learnt about the cognitive architecture of the brain by applying findings from brain-injured patients to intact brains. Even the earliest conclusions drawn from case studies in the 19th century endure today. Over time, the sophistication of methods used in cognitive neuropsychology has increased greatly, leading to ever more concrete conclusions regarding the composition, activity and structure of the human brain.

References

Aue, T., Lavelle, L. & Cacioppo, J. (2009). Great expectations: What can fMRI research tell us about psychological phenomenaInternational Journal of Psychophysiology 12 1 – 7.

Broca, Paul. (1861). Nouvelle observation d’aphemie produite par une lesion de la moitie posterieure des deuxieme et troisieme circonvolution frontales gauches. Bulletin de la Societe Anatomique 36 398–407.

Kihlstrom, J.F., 2006. Does neuroscience constrain social–psychological theoryDialogue 21 16 – 17.

Page , M (2006 ). What can’t functional neuroimaging tell the cognitive psychologistCortex 42 (3). 428 – 433.

Scoville, W.B. & Milner, B. (1957). Loss of recent memory after bilateral hippocampal lesions. Journal of Neurology, Neurosurgery and Psychiatry 20 (1) 11 – 21.

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Non-Hodgkin’s Lymphoma Disease

Non- Hodgkin’s Lymphoma or NHLs are a heterogenous group of cancers that originate from the neoplastic growth of lymphoid tissue. As in CLL, the neoplastic cells are thought to arise from a single clone of lymphocytes; however, in NHL, the cells may vary morphologically. Most NHLs involve malignant B lymphocytes; only 5% involve T lymphocytes. In contrast to Hodgkin’s disease, the lymphoid tissues involved are largely infiltrated with malignant cells. The spread of these malignant lymphoid cells occurs unpredictably, and true localized disease is uncommon. Lymph nodes from multiple sites may be infiltrated, as may sites outside the lymphoid system (extra nodal tissue).

The incidence of NHL has increased dramatically over the past decade; it is now the fourth most common type of cancer diagnosed in the United States and the fifth most common cause of cancer death.  The incidence increases with each decade of life; the average age at diagnosis is 50 to 60 years old.

Although no common etiologic factor has been identified, there is an increased incidence of NHL in people with immunodeficiencies or autoimmune disorders, viral infections including Epstein- Barr virus and HIV, or exposure to pesticides, solvents, dyes, helicobacter pylori, human T cell leukemia, and hepatitis C virus. Researchers also say that obesity could be one of the risk factors of having Non- Hodgkin’s lymphoma and those whose occupation involves chemicals and herbicides.  Prognosis varies greatly among the various types of NHL. Long term survival more than 10 years is commonly achieved in low- grade, localized lymphomas. Even with aggressive disease forms, cure is possible in at least one third of patients who receive aggressive treatments.

Symptoms are highly variable, reflecting the diverse nature of these diseases. With early- stage disease, or with the types that are considered more indolent, symptoms may be virtually absent or very minor, and the illness typically is not diagnosed until it progresses to a later stage, when the patient is more symptomatic. At these stages III or IV, lymphadenopathy is noticeable. One third of patients have “B” symptoms like recurrent fever, drenching night sweats, and unintentional weight loss of 10% or more.

Non- Hodgkin’s lymphoma usually begins with the presence of one or more swollen lymph nodes on the side of the neck, collarbone, and under the arms. The most common sites for lymphadenopathy are the cervical, supraclavicular, and mediastinal nodes, involvement of the iliac or inguinal nodes or spleen is much less common. A mediastinal mass maybe seen on the chest x- ray; occasionally, the mass is large enough to compress the trachea and cause dyspnea.  Pruritus is common; it can be extremely distressing, and the cause is unknown. Approximately 20% of patients experience brief but severe pain after drinking alcohol.

All organs are vulnerable to invasion of NHL. The symptoms result from compression of organs by the tumor, such as cough and pulmonary effusion, jaundice from hepatic involvement or bile duct obstruction, abdominal pain from Splenomegaly or retroperitoneal adenopathy, or bone pain which is from skeletal involvement. Herpes zoster infections are common. A cluster of constitutional symptoms has important prognostic implications. A mild anemia is the most common hematologic finding. The WBC count may be elevated or decreased. The platelet count is suppressing hematopoiesis. The erythrocyte sedimentation rate or ESR and the serum copper level are used by some clinicians to assess disease activity.

The actual diagnosis of NHL is categorized into a highly complex classification system based on histopathology, immunophenotyping, and cytogenetic analyses of the malignant cells. The specific histopathologic type of the disease has important prognostic implications. Treatment also varies and is based on these features. Indolent or less aggressive types tend to have small cells and are distributed in a follicular pattern. Aggressive types tend to have large or immature cells distributed through the nodes in a diffuse pattern. Staging, also an important factor is typically based on data obtained from CT scans, bone marrow biopsies, and occasionally cerebrospinal fluid analysis.

The stage is based on the site of disease and its spread to other sites. For example, in stage 1 disease is highly localized and may respond well to localize therapy like radiation therapy. In contrast, stage IV disease is detected in at least one extra nodal site. Although low- grade lymphomas may not require treatment until the disease progresses to a later stage, historically they have also been relatively unresponsive to treatment in that most therapeutic modalities did not improve overall survival. More aggressive types of NHL like

Lymphoblastic lymphoma and Burkitt’s lymphoma require prompt initiation of chemotherapy; however, these types tend to be more responsive to treatments.

Treatment is based on the actual classification of disease, the stage of disease, prior treatment, and the patient’s ability to tolerate therapy. If the disease is not an aggressive form and is truly localized, radiation alone may be the treatment of choice. With aggressive types of NHL, aggressive combinations of chemotherapeutic agents are given even in early stages.

More intermediate radiation therapy for stage 1 and II disease. The biologic agent interferon has been approved for the treatment of follicular low- grade lymphomas, and an antibody to CD20, rituximab (Rituxan), has been effective in achieving partial responses in patients with recurrent low- grade lymphoma. Studies of this agent in combination with conventional chemotherapy have demonstrated an improvement in survival as well. Central nervous system involvement is also common with some aggressive forms of NHL; in this situation, cranial radiation or intrathecal chemotherapy is used in addition to systemic chemotherapy. Treatment after relapse is controversial.

Much is known about the long term effects of chemotherapy and radiation therapy, primarily from the large numbers of people who were cured of by these treatments. The various complications are immune dysfunction, herpes infections, pneumococcal sepsis, acute myeloid leukemia or AML, Myelodysplastic syndrome or MDS, solid tumors, thyroid cancer, thymic hyperplasia, hypothyroidism,

Pericarditis, cardiomyopathy, pneumonotis, avascular necrosis, growth retardation, infertility, impotence and dental caries.

Aside from radiation therapy and chemotherapy, there are also stem cell transplantation, biologic therapy and radio immunotherapy. To diagnose Non-

Hodgkin’s lymphoma with a patient, a nurse or a health care professional should do physical examination and anamnesis or a family history of the patient which could present the possibilities that he or she could have NHL.

Most of the care for patients with Non- Hodgkin’s disease is performed in the outpatient setting, unless complications occur like infection, respiratory compromise due to mediastinal mass. For patients who require treatment, chemotherapy and radiation therapy are most commonly used. Chemotherapy cause systemic side effects like myelosuppression, nausea, hair loss, risk for infection, whereas the side effects from radiation therapy are specific to the area being irradiated. For example, patients receiving abdominal radiation therapy may experience nausea and diarrhea but not hair loss. Regardless of the type of treatment, all patients may experience fatigue.

The risk of infection is significant in patients, not only from treatment related myelosuppression but also from the defective immune response that results from the disease itself. Patients need to be taught to minimize the risk for infection, to recognize signs of possible infection, and to contact the health care professional should such signs develops.

Many lymphomas can be cured with current treatments. However, as survival rates increase, the incidence of second malignancies, particularly AML or MDs, also increases. Therefore, survivors should be screened regularly for the development of second malignancies.

The nurse should instruct the patient to stay away from strenuous activities. He should always have the time to get adequate rest. And the nurse should encourage the patient to take medications religiously, increase fluid intake. The patient should be instructed to keep himself from any injuries and falls. The nurse should raise side rails if the patient it admitted in a hospital. The family should also be instructed to just keep on showing some support towards the patient. Hhould always rie and falls. he patient to take medications religiously, increase fluid intake. the  \uld always have the time to get adequate rest. an trenous . g NOn- could have NHL. amination and anamnesis or a family histor

Having Non-Hodgkin’s lymphoma is not that good. Patients are sometimes emotionally disturbed especially if they are working and they are the ones supporting their respective families. They would also think of the payments in the electricity, hospital bills and medication. Whenever patients asked something about his/ her condition, the health care professional should be able to answer it to help the patient alleviate worrying. The patient and his/ her family should be given support groups for counseling and for them to be able to express their emotions towards the current situation they are in.h care professional should be able to answer it to ent. ng whenever swollen lymphnodes are

References:

1 Cavalli, F. (1998). Rare syndromes in Hodgkin’s and Non- Hodgkin’s. Annals of Oncology. 9 (Suppl. 5), S109- S113.

2. Coiffer, B. (2002). Rituximab in the treatment of diffuse large B- cell lymphomas. Seminars in Oncology, 29 (1, Suppl. 2), 30- 35.

3. Porth, C. M. (2002). Pathophysiology: Concepts of altered health states (6th Ed.).            Philadelphia: Lippincott Williams & Wilkins.

4. Skeel, R. (Ed.). (1999). Handbook of Cancer Chemotherapy (5th Ed.).

Philadelphia: Lippincott Williams & Wilkins

5. Smeltzer, Suzanne, and Brenda G. Bare. Medical- Surgical Nursing. Lippincott Williams & Wilkins, 2004.

 

 

 

 

 

 

 

 

 

 

 

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Dementia: Alzheimer’s Disease and Social Care Diploma

Unit DEM 301 Understand the process and experience of dementia This unit provides you with the knowledge on the neurology of dementia including the causes, difficulties and needs of the person with dementia. This will help to support your understanding of how people may experience dementia. With the development of improved health care and healthier lifestyles, people are living longer. With an increase in an ageing population come age-related conditions such as dementia. Age is not the only cause of dementia as you will discover within this unit. In this unit you will learn about: ?? the neurology of dementia ?? he impact of recognition and diagnosis of dementia ?? how dementia care must be underpinned by a personcentred approach. 1 Level 3 Health & Social Care Diploma 1. Understand the neurology of dementia 1. 1 Causes of dementia The word ‘dementia’ is a term which describes a serious deterioration in mental functions, such as memory, language, orientation and judgement. However, the causes are still not yet fully understood. Research in this area is ongoing and to date a number of types of dementia and their causes have been identified. The brain is a complex organ and is divided up into different areas that control different functions within the ody. The brain contains around 100 billion cells. In dementia some of these cells stop working properly. The part of the brain that this occurs in will affect how that person thinks, remembers and communicates. Senile dementia is a term that refers to dementia in people aged over 65. It is not uncommon for people under the age of 65 to develop dementia. This is known as early onset dementia. Cerebral cortex Ventricles Healthy brain Hippocampus Cortical shrinkage Moderately enlarged ventricles Mild Alzheimer’s disease Dementia is a major health condition which affects over 820,000 people in the UK. Worldwide, more than 35 illion people are estimated to have dementia, with 4. 6 million new cases being diagnosed every year. Shrinking hippocampus Severe cortical shrinkage Severely enlarged ventricles Types and causes of dementia Alzheimer’s disease Many people ask if dementia and Alzheimer’s disease are the same thing. The short answer is no. Alzheimer’s disease is the most common cause of dementia. It is responsible for approximately two-thirds of dementia in older people. Dementia is a contentious topic, with many proponents wishing to enable rights and choices of individuals with dementia
Alzheimer’s is caused by nerve cells dying in certain areas of the brain. In addition to this, the connections between affected nerve cells deteriorate. As he disease progresses, it spreads and affects cells in other parts of the brain. The cause of the brain cells dying and the deterioration of the connectors is not fully known. 2 Severe Alzheimer’s disease Severe shrinkage of hippocampus Brain affected by dementia and unaffected brain. Vascular dementia Vascular dementia is a form of dementia caused by damage to the brain through deprivation of oxygenated blood. Oxygenated blood is carried around your body and brain through arteries. Deoxygenated blood is carried through your body in veins. It is these arteries and veins that make up part of your vascular system.

When an organ in your body is deprived of blood, that organ (or part of it) will die. This is what happens to the brain in vascular dementia. The conditions which can cause these problems are preventable and include high blood pressure, heart problems, diabetes and high cholesterol. When supporting people into leading a healthy lifestyle, it is important to bear this condition in mind, in the hopes of preventing the onset of vascular dementia. Understand dementia Rarer forms of dementia Creutzfeldt-Jakob disease (CJD) CJD is a form of dementia caused by prion disease. Prions are proteins which are found in mammals.

When these proteins cluster together in the brain, they cause brain cells to die. When these cells die they leave holes in the brain called spongiosis. Examining the brain under a microscope reveals the cells to appear spongelike. This damage to the brain causes neurological difficulties and dementia. There are four forms of CJD: • • • • sporadic familial iatrogenic variant. Although each of these conditions is very rare, their prognosis is extremely poor. The affected person’s life expectancy is radically reduced, with death occurring usually within 6 to 24 months from early diagnosis. The isease can take many years from the time it infects a person to it causing recognisable symptoms. The cause of Sporadic CJD is unknown and its onset is very fast. It affects people over the age of 50 and can cause death within a matter of months. Familial CJD is an inherited form of the disease. Its symptoms usually affect the person at an early age from 20 to 60 years. Death occurs between two and ten years of symptoms beginning. Iatrogenic CJD occurs as a result of contaminated blood or tissue entering the healthy person’s body. This can take place with corneal transplants, grafts or the use of growth hormones.

To prevent the risk of contamination, transplants are no longer taken from people known to have the disease and growth hormones are now developed artificially. Because prions cannot be destroyed using normal sterilisation procedures, any surgical instruments used on people with CJD are not used on other patients. The last form of CJD is known as Variant CJD. This form affects people at a younger age with the average age of death being 29 years. The average time the person is affected by this disease is 14 months. Variant CJD is caused by bovine spongiform encephalopathy (BSE) – a form of prion disease which affects cattle.

The person contracts this disease by eating infected beef products. Unit DEM 301 To reduce the risk greatly of infected beef products reaching the market, manufacturers now remove the animal’s brain and spinal cord from general sale. Functional skills Maths: Recording data This information can be used to record data in a chart and shows the use of working out averages for statistical purposes. Biswanger’s disease This is a form of vascular dementia in which damage occurs to the blood vessels in the deep white matter of the brain. It affects people over the age of 60 and is often as a result of long-term hypertension or high lood pressure. Dementia and learning disabilities Some people with learning disabilities are at risk of developing dementia in adult life. People with Down’s syndrome are at risk of developing Alzheimer’s disease. The risk of Alzheimer’s increases as the person gets older. It is estimated that over half of the people with Down’s syndrome will develop Alzheimer’s disease when they are in their 60s. Fronto-temporal dementia Fronto-temporal dementia is a rare form of dementia. It tends to affect younger people and is more common within men. The condition is caused by damage to the frontal lobe and/or the temporal parts of the brain.

These areas are responsible for the person’s behaviour, emotional responses and language skills. The condition includes those known as Pick’s disease, Frontal Lobe Degeneration and dementia associated with motor neurone disease. Dementia with Lewy Bodies (DLB) Lewy Bodies are tiny protein deposits which are found inside the nerve cells of the brain. These deposits alter the way the brain functions and can be found in people with either dementia or Parkinson’s disease. Approximately four per cent of the older population who have dementia are affected by DLB. This form of dementia has characteristics of both Alzheimer’s and

Parkinson’s disease. 3 Level 3 Health & Social Care Diploma 1. 2 Types of memory impairment commonly experienced with dementia Within humans, the term ‘memory’ refers to information stored in the brain. Apart from storage, it also includes the retention or keeping and recalling of that information. A person’s brain is extremely complex and can store, retain and recall many, many pieces of information for many, many years. The ease with which the person can remember information will vary depending on the subject, the person and their state of mind. If the information is unusual or interesting, they ay remember this more so than information which is uninteresting or mundane. Memory loss can be defined in different ways depending on the situation it is being used for and the type of memory which is lost. Memory loss can be the inability to retrieve information from the long-term memory. This type of memory loss usually happens when the person is distracted or is not fully concentrating when the memory is formed. Another form of memory loss is when new memories are stored within the brain replacing older memories. Think of your brain as a filing cabinet; there is only so much information you can store n it at any one time. To make room for new information, you will need to take out or discard some old information. This type of memory loss is normal and is experienced by everyone. Memory loss can also be described as the fading away of memories. This sort of memory loss can occur with telephone numbers, facts or people’s names if you have not used them for a while. Think back to when you were at school. You would have known the names of many of the students and teachers. Can you recall all of the students’ and teachers’ names now? You may barely remember what their faces looked like and you may be truggling to remember everyone’s names. This could be because you have not had any reason to remember this information. It is not something you have had to use on a regular basis. Memory loss due to the ageing process can be defined as being the shrinking of the hippocampus, which is responsible for the storage of long-term memories. The hippocampus is usually the first part of the brain which suffers damage, leading to Alzheimer’s disease. Hippocampus Location of the hippocampus. Case study Recognising normal memory loss Christine is 43 years old and is concerned about her memory. She is a very busy lady with a stressful job.

Christine is walking down the corridor at work heading to yet another meeting. She is going over in her mind what she needs to raise in the meeting and checking through her diary to see what time she needs to leave to get into town for her third meeting of the day. Carol, one of Christine’s colleagues, bumps into her and tells her that Mark has telephoned and would like to see Christine later today at 3. 15pm in the staff canteen. Christine says, ‘OK,’ and carries on to her meeting. 4 At 3. 30pm Christine is sat at her desk writing up the minutes from a meeting last week when the telephone rings.

It is Mark; he is in the staff canteen waiting for Christine and he is not very happy. He asks if she had received his message. This jogs her memory and she realises she should be in the staff canteen. She apologises and tells him she is on her way. 1. Explain in detail why you think Christine forgot about meeting Mark. 2. Why is it that Christine is able to remember what was discussed in a meeting a week ago, yet cannot remember what she was told earlier that day? Understand dementia Functional skills English: Writing; Reading In this unit there are a number of examples of case studies. These studies have all been laid out using a uitable format and attention has been paid to ensure that spelling, punctuation and grammar are accurate. You will need to use these skills when writing case studies in your place of work. You will need to read and understand both straightforward and complex texts, and use the information in an appropriate way. Within psychology, memory loss is usually defined as the inability to retrieve declarative memories from the long-term memory. An example of this could be amnesia. The person experiencing amnesia may not be able to remember facts or declarative memories, but they retain their procedural memory which is responsible or remembering skills such as riding a bicycle, reading or talking. People with dementia may experience short-term memory loss. Their ability to store, retain and recall information may be affected due to the damage of the cells within their brain. Short-term memory loss Short-term memory can differ from one person to another. Research has been carried out on this by asking subjects to remember numbers. A list of numbers is read out at approximately one per second. The subject is then asked to recall these numbers and on average it has shown that a person can remember seven consecutive numbers.

A person with dementia may have difficulties remembering things that happened only a short while ago. However, the same person may be able to remember things that happened many years ago. Other memory difficulties could include: • • • • • • a difficulty in recognising people or remembering their names the inability to find the right words for things or objects repeating conversations that they have already had asking the same question in a short space of time forgetting appointments or recent events misplacing items, forgetting where they have put things or where they are usually kept • • • • • • • • • •

Unit DEM 301 the inability to recall what they have had to eat or even forgetting they had eaten the loss of skills such as self-care, washing, dressing, putting clothes on in the wrong order, shopping and cooking the inability to judge time, thinking it is time to get up when it is the middle of the night forgetting where they live becoming unaware of their surroundings forgetting to take medication, possibly thinking they have already taken it forgetting their disabilities such as getting up to walk even though they are not able, which results in their falling an inability to have empathy which could make the erson appear selfish personality changes – if previously extrovert, they could become introverted and vice versa the loss of social etiquette including making thoughtless comments, being rude or exhibiting sexual behaviours in public. Initially people experiencing these memory losses may feel frustrated or angry with themselves. They are angry because they know that they have forgotten, and frustrated because they are unable to remember as they used to. Activity 1 Memory impairments Think about the people you support. What types of memory difficulties do they experience and how do you know about this? Functional skills

English: Speaking and listening Have a discussion with colleagues about the types of memory difficulties that people you are working with have. Ensure you take an active part in the discussion and that you show effective listening skills. It is important to keep in mind that no two people’s memories will be affected by dementia in the same way. The inappropriateness of their behaviours is caused by a physical change to the brain and therefore the person has no control over it. 5 Level 3 Health & Social Care Diploma 1. 3 How individuals process information with reference to the abilities and limitations of ndividuals with dementia The workings of the brain are very complex. As stated previously, the human brain is made up of around 100 billion cells. In the main these cells are called neurons. It may be easier to think of these neurons as switches which are either switched on or switched off. If the neuron is switched off it is resting; when it is switched on it fires electrical impulses along its body known as the axon. At the end of this axon there is a small part which releases a chemical. The chemical travels over a gap known as the synapse where it turns on another neuron. These chemicals are known as eurotransmitters. There are 60 identified chemicals involved in the brain’s activity. The following are some important neurotransmitters relating to the process of memory and associated functions. Dopamine The chemical dopamine is critical for controlling your body’s movements. If you do not have enough dopamine, you will not be able to move or control your movements very well. Dopamine also controls the flow of information from other areas of the brain, especially memory, attention and problem-solving tasks. Serotonin The chemical serotonin is the neurotransmitter enhanced by many antidepressants, such as Prozac, nd has become known as the ‘feel-good’ neurotransmitter. It has a profound effect on mood, anxiety and aggression. Acetylcholine (ACh) ACh controls activity in the areas of the brain that are connected with attention, learning and memory. People with Alzheimer’s tend to have low levels of ACh in their brain. Glutamate Glutamate is vital for making the links between neurons that are the centre of learning and long-term memory. Reading about these chemicals and what they do can help towards explaining how the person with dementia, 6 who has damage to these neurons, has difficulty with their memory.

Because the neurons are damaged or destroyed, they are not able to produce or transmit important chemicals which are required for the person to function fully. Nerve cell Synapse Axon Dendrite The amount of electricity the human brain produces when each of its neurons is firing is equivalent to a 60-watt light bulb. Left-sided and right-sided brain The collection of 100 billion cells or neurons in the brain is divided into two halves, known as hemispheres. The right side of the brain is responsible for putting information together – for example, information received from eyes. If you see a lady the information goes from our eyes to the right side of your brain, firing neurons, putting the information together so you are able to say, ‘I can see a lady. ’ The left side of the brain analyses information which is collected by the right side of the brain. It enables you to expand on what you see so you are able to say, ‘I know who that lady is, it’s my sister Michelle. ’ People with dementia who have damage to the neurons on the right side of the brain will have difficulty putting information together. They will be able to ‘see’ things, items or people, but will not be able to make the connection of what those things, items or people are.

People who have damage to the neurons on the left side of the brain tend to be affected by depression. They will have more organisational problems and will have problems using language. Understand dementia 1. 4 How other factors can cause changes in an individual’s condition that may not be attributable to dementia Experiencing a loss or reduction in memory does not always indicate a form of dementia. There are other health conditions which could affect somebody’s level of memory. These are often referred to as reversible dementias. The part of the brain that has become damaged will determine how the person will be affected.

Unit DEM 301 Drug and alcohol induced memory loss The effects of drug misuse including excess alcohol can cause damage to the neurons in the brain, resulting in neurological difficulties including memory disruptions. Myalgic Encephalomyelitis (ME) Conditions affecting memory ME, otherwise known as Chronic Fatigue Syndrome (CFS) or Post-Viral Fatigue Syndrome (PVFS) is a chronic, disabling neurological disorder. It is characterised by persistent fatigue and muscle pain. Symptoms can include cognitive problems such as loss of memory and concentration, recurrent sore throat and enlarged neck glands, disturbed sleep patterns and ersistent headaches. Brain injury Medication Injuries to the brain can be caused by external trauma such as a blow to the head, or internal factors such as a result of a stroke or aneurism. The level of brain injury can be anything from mild to severe. This can result in both short-term and long-term or permanent difficulties. Some prescription medications can have side effects which can affect somebody’s memory. Brain tumour A tumour of the brain can be benign (slow-growing, non-cancerous) or malignant (invasive, often growing rapidly and cancerous). sensation hearing movement speech, movement and sensory functions Parietal obe Frontal lobe Occipital lobe Temporal lobe Cerebellum hearing and vision Brain stem Parts of the brain and their primary functions. Diet Some foods can have an effect on a person’s memory. It is believed foods such as those containing vitamin C and sugars can have an effect on memory. Encephalitis Encephalitis is an inflammation of the brain, usually occurring as a result of viral infection. Huntington’s disease Huntington’s disease is a hereditary, neurodegenerative disorder of the central nervous system. It can cause emotional, intellectual and movement problems. The course of Huntington’s is characterised by involuntary ovement of the limbs, trunk and face, progressive loss of mental abilities, and the development of psychiatric problems. Huntington’s disease usually appears in middle age (30–50 years) but can develop in younger and older people. Hydrocephalus Hydrocephalus is usually associated with Spina Bifida and is caused by a build-up of cerebro-spinal fluid (CSF) in the brain. This condition can also be caused by infections such as meningitis, premature birth, head injury or stroke. Hydrocephalus can lead to problems with concentration, short-term memory, organisation and coordination. Lack of sleep/insomnia

People who have difficulty sleeping may experience various health problems including memory difficulties. 7 Level 3 Health & Social Care Diploma Lyme disease Lyme disease is an infectious disease caused by the bacterium Borrelia Burgdorferi. The disease is transmitted to humans through the bite of an infected tick. If left untreated, Lyme disease may affect a person’s memory. Multiple sclerosis (MS) MS occurs as the result of damage to myelin – the protective sheath surrounding nerve fibres of the central nervous system. This damage interferes with messages between the brain and other parts of the body.

Parkinson’s disease This is a progressive neurological condition, which can affect the person’s ability in talking, walking, swallowing, writing and memory. Stress Stress is the emotional and physical strain caused by your response to pressure from the outside world. Stress can affect your health in many ways, including memory difficulties. Stroke A stroke occurs because of a disruption to the blood supply to a particular area of the brain, causing damage to that area of the brain. 1. 5 Why the abilities and needs of an individual with dementia may fluctuate Each person may experience dementia in different ways.

There is no definitive direction or path that the condition will follow and there are no exact timescales in which the condition may progress. You have examined how the person’s condition will deteriorate over time, but during that time it can also fluctuate or come and go. Fluctuation of needs and abilities It is not fully known why somebody with dementia can have ‘good days’ and ‘bad days’. Part of the answer for this could be because we all have good and bad days. This very much depends on how we are feeling, how much sleep we have had, what activity we are doing and how much we want to do that activity. 8

When you are having a bad day, everything you do seems to go wrong. Could this be simply because you are feeling so negative? Can your attitude have an effect on the outcome? Think about this for a while. If you do not like doing something, it seems to take forever to get it over and done with. The time drags and your level of boredom or uninterest rises. On the other hand, when you are doing something you enjoy, the time rushes by so that before you know it the activity comes to an end. This theory could also relate to the person with dementia. If the person is doing something that is familiar to them, something that they have done many imes and have developed a routine for, the person may appear very confident and able to do it with ease. They may appear to show no signs of dementia. However, take the person out of their familiar surroundings and out of their routine, and their confusion will grow, causing their symptoms to be more obvious. Stress has been identified to have an effect on our memory. In the early stages of dementia, the person may be fully aware that they have forgotten where they have put things. This can cause their stress levels to rise, resulting in added memory difficulties, frustration and confusion.

In these earlier stages it is important for you as a care worker to give the person emotional support. Do not be tempted to take over what they are having difficulty with. Help them to calm down and think about what they are doing. The more the person becomes agitated, the greater their difficulties will become. As the condition progresses, the more support the person will require. This will include support with day-to-day activities. You can give support through reminding the person what they need to do. Do not overload them as this will increase their stress and therefore their symptoms. If the person asks you a question and epeats it several times within a short space of time, answer it as though it is the first time you have heard the question. Do not show your frustrations as this will only cause them to become upset when they see how their behaviour is affecting you. In the later stages, the person will become emotionally and physically frail. Their reliance on care will increase to the point where they are no longer able to care for themselves. They may lose their ability to eat, walk or speak, with only the occasional word being shouted or crying out. Understand dementia Unit DEM 301 2. Understand the impact of recognition and diagnosis f dementia 2. 1 The impact of early diagnosis and follow-up to diagnosis For most people, receiving the diagnosis of dementia is very distressing. It is also very upsetting for their family. Many people today still think of dementia as being a condition which causes people to go ‘mad’. It is these negative images that can add unnecessary distress to both the person and their family. funeral through the drawing up of a will. They can be encouraged and supported to sort out any bills and arrange for future bills to be paid for by direct debit so that important bills are not overlooked. The person may ind comfort in keeping busy during the initial stages and they may feel reassured that their future has been planned to meet their needs. If you are supporting somebody who is exhibiting any signs or symptoms of forgetfulness, confusion or the inability to find the right words when communicating, it is important that they see their GP. Diagnosis can be difficult to make in the early stages as the symptoms of dementia can develop slowly. They can also be similar to symptoms of other health conditions. The GP or health professional will be able to monitor any pattern of symptoms and undertake tests over a period of time o measure any changes in the person’s mental ability. A brain scan can help with diagnosis; this could be a CT scan or MRI. If a diagnosis is made, the person may be referred to a specialist for further treatment. Early diagnosis The early diagnosis of dementia is essential in order to: • • • rule out other conditions that may be treatable access advice, information and support allow the person with dementia and their family to plan and make arrangements for the future. Receiving an early diagnosis of dementia can help the person and their family to plan and prepare for the future. Although there is no cure at present, there are arious medications available which can help improve symptoms and, for some, slow down the progression of the disease. Early diagnosis can help the person to identify and access sources of advice and support for their condition. The early education of the person and their family can help them to develop a better understanding of what the future may hold. The person will have time to put their finances in order and to make wishes for their Discussing the future with the person can help with understanding and accepting. Following diagnosis, the person may want to live as independently as they can for as long as they can.

They may not appreciate someone taking over their life in these early stages where they are still able to care for themselves. To enable the person to remain as independent as possible, it may be an idea to encourage them to contact social services, if they have not already done so, to find out what support they could be entitled to. In order to aid their memory the person could place a list of important telephone numbers by their phone. This way they will always know where a telephone number is if they need it. Labels could be placed on cupboard doors to remind them of the contents. Notes could be placed n doors as a reminder to lock them. Lists could be put on a noticeboard of things to do and days to do them on, such as putting the rubbish out for the refuse collectors. 9 Level 3 Health & Social Care Diploma The most important thing to support the person with is in continuing to enjoy their life. Support them to continue with their hobbies or interests. One good activity which will help them in the future is the development of a life history book. Encourage and support them to collect together photographs of people who are important to them, events which hold important memories such as the birth of their first randchild, their wedding day or family holidays. Encourage the person to label each photograph clearly in the book so that they can look back at it at any time and be reminded of good memories. Early diagnosis can enable the early introduction of specialist services. The services may include: • • • • • • • • • • • • • family GPs – referring the person for further tests, reviewing medication district nurses health visitors community psychiatric nurses consultants memory clinics neurologists geriatricians neuropsychiatrists physiotherapists dieticians clinical psychologists speech and language therapists.

In the very early stages of dementia the person may have days or episodes of forgetfulness which could be put down to the person being off-colour or having an off day. These episodes may be masked by their ability to recall past events easily. They may be able to give a reason as to why they cannot remember what you have just said to them. They may say that the television was too loud and they did not hear you. They may even be adamant that you had not told them anything, giving rise to you questioning your own memory. The person may have difficulty understanding or following new ideas or regimes. To cover these ifficulties they may say that they preferred the old way, as it is not as confusing. They could hide occurrences of misplacing items, making out that someone has moved the item or someone has taken it. All of these events, happenings and reasons could be very genuine and indeed the person themselves may believe in what they are saying to be true. If they were all true, the person would be a very unlucky person to be experiencing all of these negative events. The likelihood of them all occurring to the same person in a short space of time would be rather remote. Recording all of these occurrences would enable you nd the team to build up a picture of the person’s mental and physical health. Recording times that they In many cases, the earlier the diagnosis and follow-up, the sooner the person can start regaining their life again. This is not to say that they will receive a cure – at this moment in time the only option open to people is acceptance and treatment in slowing down the progress of the condition. 2. 2 Recording possible signs or symptoms of dementia in line with agreed ways of working The health and well-being of a person should be monitored on a regular basis to ensure any resulting needs can be actioned without delay.

When monitoring somebody’s condition, it is important to record any findings in line with your organisation’s policies and procedures. 10 Misplacing items can be one of the first symptoms of dementia. Understand dementia needed reminding to do something or became confused or disorientated would enable you to look back and identify frequencies to ascertain if their memory is deteriorating. Involving the family When supporting somebody with dementia, it may be of immense benefit to involve the family. Encourage and support the family to keep a diary of the person’s symptoms. As a care worker, you may not see the erson as much as their family do and therefore they can help to give you a better picture of the person and their needs. The diary that the family compiles could help them and you to identify changes in the person that may be otherwise missed. The diary could also aid in monitoring any current interventions and the resulting benefits to the person. Unit DEM 301 Suggested monitoring and recording The person’s GP or neurologist may benefit from the information recorded in altering any medications or treatment the person receives. The following areas are those which it is important to monitor and record in the erson, as these will show what changes have occurred and over what period: • • • • • • • memory behaviour personality ability to cope with daily living skills care-giving strategies – have they worked? activities the person enjoys any medications they have taken that day (including prescriptions, over-the-counter and herbal remedies) with details of medication name, dosage, and when and how many taken daily. Case study Identifying dementia Geoffrey had been living in sheltered housing for a number of years following a stroke. His confidence in his own abilities since the stroke had been very low and he as often heard mumbling to himself. Geoffrey is visited every morning by the warden Leona to check that he is OK. Geoffrey always met Leona on his doorstep as he put out his empty milk bottle. One morning Geoffrey was not on his doorstep as usual, which concerned Leona. She rang his doorbell and waited. Geoffrey came to the door and greeted her with his usual smile. ‘Are you all right Geoff, you haven’t put out your empties? ’ she asked. Geoffrey nodded, scratched his head and replied, ‘I’m fine, I haven’t finished the bottle yet as I didn’t drink much yesterday. ’ ‘As long as you are all ight then,’ Leona replied, waving goodbye as she turned and walked away. The following day, once again Geoffrey was not on his doorstep. Leona rang the doorbell again and was greeted by Geoffrey still wearing the same clothes as he had on the previous day. ‘No milk bottles to put out again today? ’ she asked. Geoffrey agreed, saying he had decided to drink more water: ‘I’m cutting down on my cups of tea, getting a bit of a beer belly,’ he joked. Leona was a little concerned but then shrugged it off, believing Geoffrey was always getting his words mixed up, due to his age. As the weeks passed Geoffrey had days when he did ot put out any empty bottles, and then he would put out three or four at a time. Some days Geoffrey looked unwashed or unshaven, which was unlike him. Leona was concerned but on talking to Geoffrey she felt she was worrying about nothing. Geoffrey’s behaviour had been up and down for over 12 months when Leona announced she was changing her job and a new male warden, Patrick, would be taking over. Geoffrey did not take this news very well and he became agitated, blaming Leona for the death of his wife. Leona was very shocked by this, especially as Geoffrey had never been married. She mentioned this to Patrick during her andover and explained she thought something was not quite right but she could not quite put her finger on it. Patrick asked how long had this been going on for and then said he would take care of it. 1. After visiting each resident in the sheltered housing, what actions should Leona have taken? 2. What concerns would you have had regarding Geoffrey? 3. How would records of Leona’s visits to Geoffrey have been of benefit? 4. What actions should Patrick take now, especially regarding Geoffrey? 11 Level 3 Health & Social Care Diploma The diagnosis of dementia does not generally occur following the first visit to the GP.

Generally there is a process in which the person goes through in order to receive a definitive diagnosis. During this process it is vital that any potential signs of dementia are reported following your organisation’s policies and procedures, and in line with government guidelines. National Institute for Health and Clinical Excellence (NICE) NICE has devised detailed guidelines in supporting people with dementia. This also includes the early diagnosis of dementia. Within this guide it states that primary health care staff should consider referring people who display any signs of mild cognitive impairment (MCI) for ssessment. MCI is a relatively new term to describe those who show some difficulties with their memory but do not have dementia. Studies have shown that 50 per cent of people with MCI go on to develop dementia later in life. NICE also includes in its guidelines information regarding the diagnosis and assessment of dementia. It states that diagnosis should only be made following assessment to include: • • • • the person’s history a cognitive and mental state examination a physical examination a review of all medication including over-the-counter remedies. As a care worker, your input in reporting possible signs f dementia would go towards the person’s history. Your input can help them receive the care that they need, when they need it. It is for this reason that you should ensure timely reporting of any observations you make or concerns you may have. To report a concern, you must follow your organisation’s guidelines. If you are unsure of what these guidelines state, you should speak with your line manager as soon as possible to ensure your actions follow best practice for the person. In general terms, most reports are given to a designated member of staff. This may be your line manager, supervisor or manager.

Your verbal report should be factual and to the point. Try to avoid giving your own opinions. Although opinions can help to look 12 at and clarify various issues from differing viewpoints, they can also be unhelpful if used inappropriately. Once you have given a verbal report, you should back up what you have discussed with the appropriate person, by writing a written report. Again your written report should be factual and detail all of the actions you have taken. Some reports will have an increased impact if they are delivered in a certain way. For example, you may have been asked to monitor somebody over a set period of ime and report back your findings. Simply writing those findings down may not have the same effect as plotting your findings on a graph. A graph or chart will give a visual representation of your findings, which may give a better explanation as to the person’s mental state and any changes that have occurred. 10 Incidence of wandering 2. 3 Reporting possible signs of dementia within agreed ways of working 8 6 4 2 0 Week Reporting occurrences such as wandering can have a greater impact if plotted on a graph. Activity 2 Process of reporting Speak with your manager or line supervisor to identify our organisation’s policy and procedures on the process of reporting information. Functional skills English: Speaking and listening This discussion can be either formal or informal and can give you the opportunity to practise taking part in a one-to-one discussion. Understand dementia Reflect Imagine you, or someone you love, had just been given the news that you or they had dementia. Being honest, what would be your initial thoughts or feelings? Do you feel it is OK to feel or think this way? Is there anything you feel that society can do to help with the acceptance or understanding of dementia?

Unit DEM 301 2. 4 The possible impact of receiving a diagnosis of dementia on the individual and their family and friends Receiving news which you know will have a major impact on your future and those who are close to you can be very frightening and overwhelming. The person may feel very insecure at the time, despite possibly having family and friends around them. The impact on the person and their family and friends can vary; some may see it as a relief that the cause of their difficulties has been diagnosed, while others may be in disbelief, preferring not to acknowledge what they have been told.

Many older people fear becoming a burden on their family more than they fear death. 13 Level 3 Health & Social Care Diploma Feelings NICE requirements The person may be shocked on first hearing the diagnosis; this can often turn to denial. One theory on loss or grief shows that the process usually goes through five stages including: NICE guidelines state that following a diagnosis of dementia, health and social care professionals should provide the person and their family with written information regarding: 1. 2. 3. 4. 5. • denial anger bargaining depression acceptance. It is felt that the person may not necessarily go through ach stage in this particular order, and indeed can go backwards and forwards, repeating various stages a number of times before reaching and remaining at acceptance. The person may experience fear or the concern that they will lose control over their lives and their future. They may also fear becoming a burden on their family and friends. Some may feel guilty, blaming themselves, thinking that they could have prevented their condition happening. Whatever feelings the diagnosis creates in the person, you should encourage and support them to talk about their feelings. Some may not feel comfortable voicing heir feelings to their family and friends, preferring to talk with someone they do not know. The person’s family and friends should not be upset by this decision and should respect the wishes of their loved one. Initially the person may simply want to curl up and lock out the world around them. Family and friends need to be supportive in these situations. Telling the person to ‘get a grip’ or that what they are doing is silly is not going to be of any benefit – in fact, it will often make things worse. 14 • • • • • • • the signs and symptoms of dementia the course and prognosis of the condition treatments ocal care and support services support groups sources of financial and legal advice, and advocacy medico-legal issues, including driving local information sources, including libraries and voluntary organisations. Any advice and information given to the person and their family should be recorded in the person’s care notes. The confidentiality of the person should be respected if they decide they do not wish any information to be given to their family. Understand dementia Unit DEM 301 3. Understand how dementia care must be underpinned by a person-centred approach 3. 1 Person-centred and nonperson-centred approaches to ementia care It is important to remember that people with dementia are individuals first, with their condition of dementia coming second. They may also be mothers, fathers, brothers, sisters, sons or daughters. They may have led a fulfilling life before the condition of dementia took hold of their memories and personality. How could the care of any person be anything other than individual, specific to their needs, involving and respecting their views on how they want their care to be delivered? Person-centred care is a way of providing care with the person at the centre of everything you do. Another way f describing it is individualised care – care that is given to the person according to their needs, wishes, beliefs and preferences. One would hope that gone are the days when everyone in a care home got up at the same time, ate their breakfast at the same time, got washed and dressed at the same time, even going to the toilet at the same time. These regimented routines of care homes were devised for the benefits of the staff, not the people being supported. The day revolved around tasks, duties that had to be met, more often than not putting the people’s specific needs at the end of the priority list.

If you needed support, which type of care home would you choose? Earlier on in this unit we looked at how dementia can affect people and identified that no two people would necessarily follow the same process through the condition of dementia. This being the case should automatically exclude all people with dementia being treated in the same way. Studies have shown that a person-centred approach can help reduce agitation in the person with dementia. Agitation is often caused by the person’s frustration in not being able to express themselves. The expression could be one of sadness, pain, thirst, hunger or tiredness.

Other studies on a person-centred approach have shown that the person often remains living in their own home for longer. A person-centred approach can also ensure that the person does not endure the degrading, discriminatory and abusive practices which could otherwise occur. People and all those involved in their care should feel safe, feeling that they are a part of what is going on, receive continuity of care, have purposeful goals which they are supported to progress towards and have a feeling that they do matter. How does a person-centred approach benefit the person? As a care worker, you should identify the specific needs f the person with dementia. These needs could arise from their gender, ethnicity, age, religion and personal care. Other needs could also arise from their physical health or physical disability, any sensory impairment, communication difficulties, problems resulting from poor nutrition, poor oral health or learning disabilities. The person’s needs should be identified with input from the person, their family, friends and any other persons that may be important in that person’s life. Once the person’s care needs have been identified, plans should be made to draw up a support plan which will describe how those needs will be met.

As with the assessing of needs, the person must be at the centre of the support planning process. Nothing should be planned for them without them. 15 Level 3 Health & Social Care Diploma Case study The importance of a person-centred approach It is approaching lunch time but Mrs Lancaster is not really hungry. She would like a drink and would prefer to remain in her room as she is comfortable and her favourite television programme is about to start. Mrs Lancaster is not able to voice these preferences verbally, as she finds it very difficult to verbalise and so has given up trying. Tracy, one of the senior care workers, enters

Mrs Lancaster’s room and makes her jump, as Mrs Lancaster did not hear Tracy entering. ‘Come on then love, your dinner’s ready,’ Tracy tells Mrs Lancaster. She then promptly holds Mrs Lancaster under the arm and says, ‘Up you come chum. ’ Mrs Lancaster reels back in pain and cries out. Tracy responds saying, ‘Don’t be silly, now come on, your dinner’s going to get cold,’ again pulling up under Mrs Lancaster’s arm. Mrs Lancaster pulls away, which makes Tracy annoyed. She bends down and puts her face close to Mrs Lancaster’s and says, ‘I’ll leave you here to starve if you carry on like that. ’ Mrs Lancaster cannot take any more bullying or hreats from Tracy so she brings her head back and then sharply forward, head-butting Tracy. ‘You nasty woman, you ought to be locked up doing things like that! What have I ever done to you to deserve treatment like that? ’ Tracy shouts, leaving the room with a bloodied nose. 3. 2 Different techniques to meet the fluctuating abilities and needs of the individual with dementia people with dementia. Seize the challenge and look forward to the unexpected. As the saying goes, ‘variety is the spice of life’. 1. Explain six things in detail that could have possibly led to Mrs Lancaster head-butting Tracy. 2.

What should Tracy have done to prevent this occurrence? 3. Describe a way Mrs Lancaster could be supported to communicate in future. 4. Describe how her care could be given using a person-centred approach. Knowing the person Many people with dementia are able to live in their own homes for most of their lives with care being given to them by their families. It is important that the person is supported to recognise that the condition that they have is not the fault of anyone, especially not their own. When supporting the fluctuating needs and abilities of the person, it is very important that you recognise that hey are not responsible for the things that they do. It is not the person who is spitting out their food; it is the condition’s effects on the person’s ability to communicate which is preventing them from saying, ‘I don’t like that. ’ It is not the person who is constantly wandering around the environment; it is the condition that has taken away their spatial awareness. As a support worker, you must focus on the skills and abilities that the person has, rather than those that they have lost. Ensure that you are fully aware of and respect the person’s background, their history, likes and dislikes.

Be prepared for changes and adapt a flexible approach. No two days may be the same in supporting 16 By learning about each person’s history and background, you can design the care and support you provide around their specific needs. For example, the person may have been a sergeant major in the army, which could account for his shouting out his orders. The person may have experienced a traumatic event in their lives such as being trapped in a collapsed building, which could account for them becoming agitated and screaming when the lights are switched off in their bedroom at night. Without this background knowledge, nd more importantly understanding, the person who shouts his orders may be wrongly labelled as being noisy and dictatorial. The person who screams in the dark may be wrongly labelled as disruptive and attention-seeking. A person’s physical condition can be affected by their dementia. Their mobility may be reduced as may the person’s ability to maintain their own personal care or diet. Combining these factors can increase the person’s susceptibility to other illnesses such as chest infections or physical conditions such as pressure sores. Understand dementia Ensure the person’s support plan is kept as up to date s possible and shows alternative methods to use for various fluctuations in their support needs. Support other care workers by sharing proven practices. As a support worker, you may have identified triggers to somebody’s behaviour. Do not keep this information to yourself; inform other care staff and have it recorded in the person’s support plan. This would be the same for identifying any new method or way of supporting the person to meet their fluctuating needs. Provide a stable environment and suitable surroundings One of the main triggers resulting in somebody with dementia becoming agitated and confused is a change n their routine. Any changes to the person’s life or daily routine can cause them to become unsettled, which could lead to inappropriate behaviours. To ensure stability it is important to: • • • • have consistent, regular staff. Unfamiliar faces can cause the person great upset. Ensure they know the staff and ensure the same staff member provides care to the person in their own home maintain a familiar environment. It is an eventuality in everyone’s life that their surroundings will change at some point. This could simply be through redecoration or changes in furniture. Where possible, if decoration needs to be undertaken within the erson’s environment, try to make the new decor similar if not the same as it was previously. If relocation is required for the person, ensure this is minimised by confirming the suitability of the new location. This will save on the person needing to be relocated again due to the environment not being suitable for their needs ensure the person is in a non-stressful, constant and familiar environment establish a regular routine, regular physical activity and adequate exposure to light to improve any sleep disturbances. Specific strategic support People with dementia may behave in a way that is completely out of character.

Some of these behaviours can be disturbing to onlookers and especially the person’s family, seeing their loved one behaving in a way they have never seen before. The following are examples of the types of behaviours people with dementia may display. Unit DEM 301 Wandering People with dementia may tend to walk or wander apparently aimlessly for a variety of reasons. This could be because they are bored or they feel they need to escape or get out of the environment they are in. The person may simply need to use the bathroom but cannot remember where it is. On occasions this wandering may take them out of the house or even own the street. This could lead them into becoming ‘lost’ if they are unable to find their way back home. For most people, wandering may only be a short phase that they go through. And, although little comfort at the time, people with dementia often retain a good degree of road sense and are seldom involved in traffic accidents. To reduce incidents of wandering, promote physical activities to reduce the person’s boredom and to help use some pent-up energy. What dangers could wandering have for somebody? Incontinence Loss of bowel or bladder control usually occurs as the dementia progresses. Sometimes these accidents may appen because the person cannot remember where the bathroom is or cannot get there in time. If the person does become incontinent, you need to help them to maintain their dignity and respect by being understanding and reassuring. Incontinence pads, sheaths or catheters can be obtained to help keep the person free from unnecessary embarrassment and frustration. 17 Level 3 Health & Social Care Diploma Agitation Agitation can include behaviours such as sleeplessness, verbal or physical aggression and irritability. These types of behaviour often increase with the stages of dementia and can become quite severe.

Agitation may be triggered by a variety of factors including environmental factors, fear and tiredness. Most often agitation is triggered when the person feels as if they are no longer in control of the situation. You can help reduce episodes of agitation by reducing the intake of caffeine, sugar and processed foods. The reduction of noise or crowds can also help, as does the maintenance of the person’s routines. is a list for further reading which will help your knowledge and understanding further. Doing it well Meeting the needs of people with dementia • Know the person well, including their history and background. Keep their support plan up to date. • Provide a stable environment and suitable surroundings. • Ensure specific strategic support. • Improve your knowledge and understanding. Repetitive speech or actions It is a common occurrence with those who have dementia to repeat a word, statement, question or activity more than once in a short amount of time. This repetition can be frustrating and stressful to the care giver and their family. Repetition is often as a result of the person becoming anxious, bored, fearful or agitated. One way of reducing this is to provide them with reassurance. Alternative strategies could include isplaying reminders of activities around their home such as ‘Dinner is at 6:30pm’ or ‘Dave comes home at 5pm. ’ This may assist with reducing anxiety and uncertainty about anticipated events. Paranoia People with dementia may suddenly become suspicious, jealous or start accusing others of things. When this happens, the person will believe in what they are saying and therefore you should not try to argue or disagree with them. Stay calm and encourage the person to calm down. Ask them what is wrong and let them know that you are there to help them. Improve your knowledge and understanding Many organisations have helpful information on nderstanding and supporting people with dementia. Set yourself a goal to develop your practices through research, talking to people who are in the early stages of dementia or family and friends of those who have it. Learning about dementia from those who have firsthand experience is often more beneficial than reading a book, although books have the benefit of being portable and accessible at any time. At the end of this unit there 18 3. 3 How myths and stereotypes related to dementia may affect the individual and their carers Dealing with the difficulties that come with the diagnosis of dementia is not going to be made any asier with the myths and stereotypes that society has created. Within society, dementia is often seen as a condition that causes the person to require 24-hour care in a secure environment so they cannot get out and wander aimlessly. People who are newly diagnosed with the condition are sometimes disbelieved because they appear ‘normal’ and are dribbling or babbling. Some myths or falsehoods can create an unrealistic hope within the person or their family. Some of these untruths profess to offer cures or preventions. The following information can help you to identify fact from fiction. Q – Can using aluminium saucepans affect the risk of eveloping Alzheimer’s? A – No, there is no convincing evidence that cooking with aluminium saucepans increases the risk of developing Alzheimer’s. Q – Is it true that people who follow a healthy lifestyle reduce the risk of developing dementia? A – Yes. Research shows that people who enjoy a healthy lifestyle by eating a well-balanced diet, not smoking and taking regular exercise reduce their chances of developing dementia. Recent research has shown that being healthy in mid-life can help lower our risk of developing dementia as we age. Understand dementia Q – Can Ginkgo Biloba help people with dementia? A – No.

Unfortunately, the latest evidence shows that Ginkgo Biloba has no benefit for people with dementia. Q – Does eating meat have any connection with developing Alzheimer’s? A – There is no convincing proof that eating meat is linked to developing Alzheimer’s. Q – Do people who have dementia become childlike? A – No; it is very important to remember that people with dementia are adults and should be treated with the dignity and respect other adults receive. Many people, quite wrongly, have stereotypes when it comes to dementia. It is these stereotypes that can become the fear of reality for people newly diagnosed ith dementia. Sometimes it is the person’s own stereotyping of dementia that they have to face. Facing and resolving this can only occur with education and acceptance. Unit DEM 301 3. 4 Ways in which individuals and carers can be supported to overcome their fears Research has shown that many people fear the thought of developing a form of dementia. The worry of losing one’s identity, independence and mind for some is a greater fear than the fear of death. Worrying about a condition that you may not develop seems futile. Worrying about a condition which you have developed will not do your health much good.

Simply telling somebody who has received a diagnosis of dementia or their family not to worry is insufficient. Advising the person and their family to talk about their fears will help towards them overcoming any uncertainties. Ignoring the condition or pretending it is not happening is simply denial. To help all those involved to overcome worries for the future, the person and their family should be supported to learn the truth, what they can expect from the future. Activity 3 Understand the condition What’s in a name? The person and their family should be supported to develop a true understanding of the condition they are acing. Information can be obtained from GPs’ surgeries, health centres, libraries and the Internet. When obtaining information from books or the Internet, you need to ensure it is up to date and reliable. Internet sites run by organisations such as the Alzheimer’s Society or NHS Direct can be seen as reliable sites, as can educational sites such as those ending with . org. Some of the facts relating to dementia do not always make for easy reading; however, the person and family need to know what to expect. Skirting around these issues will not enable the preparation that may be required. This could lead to a bigger shock when it ctually happens, which would not do anybody any favours. Devise a simple questionnaire which you can either send out to colleagues or staff within your organisation, or give to your family and friends. Ask questions such as, ‘Give the first word that comes into your head when you hear the word “dementia”. ’ Include a few questions that relate to the myths around dementia to see if your colleagues or family know the truth or not. Compile the results from your questionnaire and discuss these with your assessor. People’s inappropriate views or opinions on dementia often arise from ignorance. For many, the only portrayal hey have of dementia is that which they see on television. Storylines shown in films are often of people in the advanced stages of dementia. If this is the only perspective you have, then there is no wonder why society looks at this condition in the way it does. If the individual newly diagnosed with dementia or their family has only ever known of dementia in this way, then their fears will understandably be heightened. Encourage future planning Once the person and their family are aware of how dementia may affect the future, they should be supported to think ahead and be ready for the changes that will follow.

The person and their family will need to prepare things not just materially but emotionally as well. At some point the person may require support with toileting and other personal care needs. They may not want their family attending to this sort of personal care, 19 Level 3 Health & Social Care Diploma preferring to have a care worker attend to their needs at home. There may come a point where the person is unable to stay in their own home due to the advancement of their condition. The fear of this eventuality can create a lot of worry for them. Supporting the person to plan for this can help allay those fears.

They and their family could be supported to identify a care home which the person may move into in the future. Simply knowing that this step has been arranged can help them feel a little easier, knowing that they will not be placing a burden on their family. Making life easier The person may have received a diagnosis of dementia because of their current memory difficulties. The family may worry that the person will not be able to cope very well at home, forgetting to take their medication, forgetting to lock doors and windows when going out and so on. These sorts of worries for the family will not necessarily lessen.

As each day passes they may worry. As each day passes the person’s condition may increase, making the family worry all the more until it becomes a vicious circle. To help reduce these fears, the person can be supported to remain as independent as possible at home with the use of notes, labels, lists – any memory joggers. The environment in which the person lives can be made safer – for example, installing grab rails or an emergency pull cord system. Making these minor changes to the person’s home may reduce the natural worries of the family with regards to their loved one’s safety. Dealing with the diagnosis of dementia is never going to e easy. Some people and their families may benefit from receiving counselling. This can often b

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Industrial Injuries and Occupational Diseases

MINISTRY OF EDUCATION AND SCIENCE OF THE REPUBLIC OF KAZAKHSTAN INTERNATIONAL UNIVERSITY OF INFORMATION TECHNOLOGIES Essay Industrial injuries and occupational diseases Checked by: Utepov T. Y. Done by: Gilmanov N. E. Alamty 2012 Industrial injuries and occupational disease. An industrial injury covers of two different forms: Accidents at work  and Occupational diseases. An accident is a physical or mental injury following an incident or exposure. The incident or exposure has to be sudden or last no more than 5 days.

An accident can be recognized as an industrial injury if the injury occurred due to your work or working conditions. In other words, there has to be causality between your work and the cause of the injury. If you accidentally get injured in the workplace, the injury is not necessarily caused by your work. Example: You get up from a chair and get a prolapsed disc. Occupational disease is a disease that is caused by the work or working condition. The disease may develop due to short- or long-tem exposures. For example your hearing reduced by working several years in noisy environment.

In this essay I want to focus on industrial injury and generally occupational disease. Common causes of industrial injuries like poor ergonomics, manual handling of heavy loads, misuse or failure of equipment, exposure to general hazards, inadequate safety training and clothing. They causes may damage human organs like spine, lungs, eyes, skeleton and skin. There are many methods of preventing or reducing industrial injuries, including anticipation of problems by risk assessment, safety training, control banding, personal protective equipment safety guards, mechanisms on machinery, and safety barriers.

In addition, past problems can be analyzed to find their root causes by using a technique called root cause analysis. According to definition, an occupational disease is a disease or disorder that is caused by the work or working conditions. This means that the disease must have developed due to exposures in the workplace and that the correlation between the exposures and the disease is well known in medical research. Or put in another way, it must not be likely, beyond reasonable doubt that the disease was caused by factors other than work. Examples of occupational diseases: Tennis elbow, Allergy, Hearing loss, Asthma, etc.

Also, there are several methods to preventing occupational disease organization must organize safety training, control banding, and provide personal protective equipment safety guards and mechanisms safety barriers. In addition it will be useful if all problems will be analyzed and found cause to solve it. Summing up, occupational diseases are widely known industrial injuries. Workers in every occupation can be faced with hazards in the workplace. Preventing work diseases and accidents must be the goal of occupational health and safety programmers. In order to provide safety and health organizations must possibly limit harm from hazards.

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Endometriosis

Endometriosis is a painful, chronic disease that affects at least 6. 3 million women and girls in the U. S. It occurs when tissue that lines the uterus is found outside the uterus, usually in the abdomen on the ovaries, fallopian tubes, and ligaments that support the uterus. The cells of endometriosis attach themselves to tissue outside the uterus and are called endometriosis implants. In endometriosis, displaced endometrial tissue continues to act as it normally would; it thickens, breaks down and bleeds with each cycle.

And because this displaced tissue has no way to exit your body, it becomes trapped. Surrounding tissue can become irritated, eventually developing sace tissue and adhesions. The cause of endometriosis is unknown. One theory is that the endometrial tissue is deposited in unusual locations by the backing up of menstrual flow into the fallopian tubes and the pelvic and abdominal cavity during menstruation; also called retrograde menstruation.

Another possibility is that areas lining the pelvic organs possess primitive cells that are able to grow into other forms of tissue, such as endometrial cells. Another cause of endometriosis might be the direct transfer of endometrial tissues during surgery and may even be seen in surgical scars. Transfer of endometrial cells via the bloodstream or lymphatic system is the most likely explanation for the rare cases of endometriosis that has develop in the brain and other organs distant form the pelvis.

Research by the Endometriosis Association revealed a startling link between dioxin exposure and the development of endometriosis. Endometriosis affects women in their reproductive years. The exact prevalence of endometriosis is not known, since many women may have the condition and have no symptoms at all. While most cases of endometriosis are diagnosed in women aged around 25-35 years old, endometriosis has been reported in girls as young as 11 years old.

Most women who have endometriosis, in fact, do not have symptoms; the most common symptoms are pain before and during periods, pain with sex, infertility, fatigue, painful urination during periods, and painful bowel movements during periods. Pelvic pain however depends partly on where the implants of endometriosis are located. Endometriosis can be one of the reasons for infertility for otherwise healthy couples. Endometriosis can be suspected based on symptoms of pelvic pain and findings during physical examinations in the doctor’s office.

Unfortunately, neither the symptoms nor the physical examinations can be relied upon to conclusively establish the diagnosis of endometriosis. Tests to check for physical clues of endometriosis include: Pelvic exam, ultrasound, and laparoscopy. Treatment for endometriosis is usually with medications or surgery. The approach you and your doctor choose will depend on your age, severity of symptoms, severity of disease and whether you want children in the future.

There are also hormonal therapies used to treat endometriosis like: hormonal contraceptives, Gonadotropin-releasing hormone, danazol, medroxyprogesterone, aromatase inhibitors, conservative surgery and hysterectomy. Endometriosis is more common in infertile, compared to fertile women. However, the condition usually does not fully prevent conception. Most women with endometriosis will still be able to conceive, especially those with mild to moderate endometriosis. It is estimated that up to 70% of women with mild and moderate endometriosis will conceive within three years without any specific treatment.

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Edward Jenner and Smallpox

Despite all of the controversy around vaccinations, vaccines have been around for nearly 200 years and are known to have saved millions of lives by preventing a person from infectious diseases through inoculation. The world’s first vaccine, the vaccination for smallpox was developed in 1796 by Edward Jenner, a doctor from England. Smallpox, which dates back to 1350 B. C. , is an infectious and contagious disease that plagued much of Europe and North American colonies during the 17th and 18th century. Smallpox claimed more than million deaths in Europe and Mexico before development of the vaccination.

Dr. Jenner’s scientific research and observations led to the eradication of smallpox in 1979. The purpose of this paper is to examine one of the greatest achievements in public health, the smallpox vaccination and the man responsible for it, Dr. Edward Jenner. This paper will also focus on the effects that the smallpox vaccination has had on public and community health and how the process of immunization from infectious diseases has saved millions of lives today. What is Smallpox Smallpox is an infectious and contagious disease, which is caused by the variola virus.

The virus, which has two forms, variola major and variola minor, was referred to as the speckled monster because of red, pustule, raised lesions that appeared on a person’s skin. Aside from the skin lesions, smallpox is characterized by typical flu symptoms such as fever, fatigue, muscle aches, malaise, and headache. Smallpox is an airborne transmitted infection, which multiplies itself in the lymph nodes while moving from cell to cell. A person is said to be contagious until the last lesion scab falls off. Whereas a cure for smallpox does not exist, the only form of prevention is vaccination (Barquet & Domingo, 1997).

Edward Jenner and His Developments Edward Jenner, who was born on May 17, 1749 in England, developed an interest in science and nature during his early years. He worked as an apprentice under George Harwicke, in which he developed the interest in cowpox. Jenner went to London at the age of 21 to become a student of John Hunter, the most prestigious surgeon in England, Here, Jenner learned that if a person had cowpox he or she could not contract smallpox (Stern, 2005). Through Jenner’s apprenticeship with Hunter, he began learning surgical techniques and the use of scientific methods and observation.

After publishing several scientific studies and learning through observations, Jenner’s interest in smallpox grew and it was at this point in which he developed his hypothesis; “Cowpox protected a person from the human disease smallpox” (Barquet & Domingo, 1997, p. 639). Developing the Smallpox Vaccine Sparked by the interest in his hypothesis and the overwhelming plague of smallpox, Jenner decided to perform an experiment to test his hypothesis. Jenner came into contact with Sarah Nelms, a dairymaid who had contracted cowpox through an infected cow.

To test his hypothesis, “Jenner extracted fluid from the pustules on Nelm’s hand and used that same fluid to inoculate an 8-year-old boy through two inch incisions on the boy’s arm” (Barquet & Domingo, 1997, p. 639). A few weeks later, Jenner injected fluid from a smallpox lesion into the arm of the same boy. This is known as variolation. The variolation did not produce a reaction and Jenner confirmed that the boy was protected against smallpox. As a result of Jenner’s studies, research, and observations, the smallpox vaccine was developed (Stefan, 2005).

The Effect of the Smallpox Vaccine on Public and Community Health Upon the publication of Jenner’s inquiry, skepticism arose as Jenner began a nationwide survey to support his findings. Other physicians began vaccinating through Jenner’s method and the theory was confirmed. Those who were previously infected with cowpox and received variolation did not find themselves stricken by smallpox. The vaccination era had begun as news of the inquiry spread to the United States where the method was tried and confirmed once again by Benjamin Waterhouse, a Harvard Medical School professor (Barquet & Domingo, 1997).

According to Barquet and Domingo (2005), “President Thomas Jefferson had 18 members of his family vaccinated and supported the theory that the vaccine preserves individuals from smallpox” (p. 640). President Jefferson later appointed Waterhouse as the “vaccine agent in the National Vaccine Institute, an organization to establish vaccination in the United States” (Barquet & Domingo, 1997, p. 640). Public and Community Health Today Several years after Jenner’s discovery, scientists had begun to develop new vaccines.

Protesting began as antivaccinationists believed that vaccinating violated a person’s privacy. In 1905, the United States Supreme court ruled that “The need to protect the public health through compulsory smallpox vaccination outweighed the individual’s right to privacy” (Stern & Markel, 2005, p. 617). The World Health Organization (WHO) certified the eradication of smallpox in 1979. As other vaccinations emerged, such as vaccines for polio, diphtheria, measles, mumps, and rubella, people commonly worried about the safety and efficacy of these vaccinations.

Today, many parents are under the impression that autism is linked to a preservative called thimerosal, which was used in many vaccinations such as DTP and Hepatitis B vaccines. Upon scientific studies, no connection was found. However, in 1999 the United States Food and Drug Administration stopped licensing vaccines that contained thimerosal (Stern & Markel, 2005). Conclusion The development of the smallpox vaccine and other immunizations are considered to be one of the greatest achievements in public health.

Disease prevention is a major necessity of public and community health. Through extensive research, scientific studies, and observation, Edward Jenner paved the way for the evolution of public health. To date, vaccinations have saved millions of lives by protecting people against polio, diphtheria, measles, mumps, rubella, and smallpox. Although many people are skeptical about the safety and efficacy of immunizations, choosing not to be immunized puts not only the individual at risk but also other people at risk of contracting an infectious disease.

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Legionnaire`s disease

Since the identification of Legionella two decades ago, a significant amount of information has accumulated concerning the microbiology, epidemiology, clinical manifestations, control, and therapy of infections caused by these organisms. The number of species in the genus Legionella has increased dramatically. Legionella is considered to be responsible for 2–13% of cases of community-acquired pneumonia requiring hospitalization (Brieman and Butler, 1998).

The various Legionella species can cause two distinct diseases: a severe form of pneumonia known as Legionnaire disease or a less serious, influenza-like illness known as Pontiac fever, which is generally recognized only during those outbreaks in which a cluster of cases of Legionella pneumonia sparks an epidemiologic investigation that uncovers these less serious infections.

Microbiology

The organism is a Gram-negative bacillus. There are currently 42 described species of Legionellae representing 64 serogroups in the family (Benson and Fields, 1998). Legionellaceae and the genus Legionella. The phenotypic characteristics of Legionellae are defined by growth requirements, and biochemical characteristics including fatty acid analysis and ubiquinone analysis, protein profiles, carbohydrate analysis, serology, monoclonal antibodies, and molecular techniques (DNA-DNA hybridization).

L. pneumophila is a facultative intracellular pathogen that invades and replicates within free-living protozoa (i.e. amoeba) and mammalian cells (Benson and Fields, 1998). Within natural environments, L. pneumophila can persist as a free-living microbe, but it replicates exclusively as an intracellullar parasite within amoeba. L. pneumophila causes Legionnaire’s disease by replication in alveolar macrophages and monocytes.

During infection the Legionnaire’s disease bacterium survives and multiplies within a specialized phagosome that is near neutral pH and does not fuse with host lysozymes. Studies show that the regulation of macrophage resistance versus susceptibility to infection is mediated by specific genetic mechanisms. The induction of cytokines by Legionella can activate immune cells, especially T helper cells. Activated macrophages restrict the growth of Legionella (Segal and Shuman, 1998)

Epidemiology

Cases can occur in clusters or sporadically from the community or in the hospital setting. The disease is much more common than previously appreciated with at least 13 000 cases estimated to occur per year in the United States (Brieman and Butler, 1998). There may also be local environmental factors that are important and still not well defined.

Although immunosuppressed patients and specifically transplant patients seem to have a higher risk of developing Legionnaire’s disease, there are many more non-immunosuppressed individuals in the community who may be infected with Legionella. nvestigations into community outbreaks still find cooling towers to be a source of the Legionella

Clinical manifestation

Luttichau et al(1998) investigated an outbreak of Pontiac fever in children and adults, caused by a contaminated whirlpool. The authors isolated L. pneumophila serogroup OLDA from one of the children and believe that this represents the first reported culture-confirmed case of Pontiac fever. The outbreak was characterized by a short incubation period, influenza-like symptoms, and rapid recoveries, all features typical of Pontiac fever.

The median incubation period for the children was shorter (43 h) than for the adults (70 h). The median duration of the illness was 87 h for the children versus 61 h for the adults. The most common symptoms noted by the adults were fever, dizziness, headache, cough, fatigue, arthralgia and abdominal pain. Ear pain and rash were more common in children.

Diagnosis

The diagnosis of Legionnaire’s disease remains troublesome in many hospitals. Serological studies are useful too late for the clinician and cultures must be incubated for at least 3 days. Legionella urinary antigen assays are useful early in clinical disease but the kits that are currently available only identify patients with disease caused by L. pneumophila serogroup 1. Recent improvements in the methodology for performing polymerase chain reaction on bronchoalveolar lavage solutions are encouraging (Chiba etal, 1998)

Treatment

Antimicrobial agents generally considered clinically effective for Legionella infections include macrolides, fluoroquinolones, tetracyclines, and rifampins. In a study several new antimicrobial agents with in-vitro activities against Legionellae that were found  better than those of erythromycin; included were a new rifampin-like drug, rifapentine, dalfopristin-quinupristin, and a new ketolide (HMR3647).

The advantages of the quinolone agents include bactericidal activity against Legionella and a prolonged post-antibiotic effect whereas erythromycin is only inhibitory. In an additional study using HL-60 cells to evaluate new macrolides, Stout et al (1998)documented that the most active inhibitors of L. pneumophila intracellular multiplication were (in order of activity) azithromycin, erythromycin, roxithromycin, dirithromycin and clarithromycin.

In a recent editorial, Edelstein (1998) suggested that azithromycin or one of the more active fluoroquinolones should be used in preference to erythromycin for the treatment of Legionnaire’s disease in immunocompromised patients, based on their greater in-vitro activity as well as their better pharmacodynamic properties. In addition to producing a potentially better outcome, these agents will often improve patient compliance because of fewer side-effects and the shorter duration of therapy.

Conclusion

Infections caused by Legionella spp. are a significant cause of morbidity and occasionally mortality. The projected number of cases of infection caused by Legionella spp. are much greater than those reported to CDC’s surveillance system, indicating both underdiagnosis and under-reporting.

Hopefully, new information concerning the molecular biology and pathogenesis will provide a better understanding of infection caused by these organisms. Recent studies suggest that the newer macrolides and newer fluoroquinolones are the optimal agents for these organisms.

References

1 Benson RF, Fields BS. Classification of the genus Legionella. Semin Respir Infect 1998; 13:90-99. A comprehensive update of the microbiology and tetonomy of Legionellae

2 Breiman RF, Butler JC. Legionnaire’s disease: clinical, epidemiological, and public health perspectives. Semin Respir Infect 1998; 13:84-89

3 Segal G, Shuman HA. How is the intracellular fate of the Legionella pneumophila phagosome determined? Trends Microbiol 1998; 6:253-255.

4 Luttichau HR, Vinther C, Uldum SA, Moller J, Faber M, Jensen J. An outbreak of Pontiac fever among children following use of a whirlpool. Clin Infect Dis 1998; 26:1374-1378.

5 Chiba Y, Okamoto H, Nagatomo A, Kunikare H, Watanabe . Legionnaire’s disease diagnosed by bronchoalveolar lavage. Int Med 1998; 37:153-156.

6 Stout JE, Arnold B, Yu VL. Activity of azithromycin, clarithromycin, roxithromycin, dirithromycin, quinupristin/dalfopristin and erythromycin against Legionella species by intracellular susceptibility testing in HL-60 cells. J Antimicrob Chemother 1998; 41:289-291

7 Edelstein PH. Antimicrobial chemotherapy for Legionnaire’s disease: time for a change. Ann Intern Med 1998; 129:328-330.

 

 

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Disease and Conditions of the Reproductive System

Unit Seven Workbook Assignment Chapter 12: Diseases and Conditions of the Reproductive System Assignment: For each scenario below, outline the appropriate patient teaching you would perform. First, review the “Guidelines for Patient-Teaching Exercises” found on page iv in the “Introduction”. 1. SYPHILIS A patient has been diagnosed with syphilis. The practice has printed instructions for patients diagnosed with this condition. The physician has instructed you to provide the patient with the printed information and to review it with her.

How do you approach this patient-teaching opportunity? First, I would sit down with the patient and read the printed instructions to the patient. I would emphasize the importance of finishing the coarse of medication, even if the symptoms improve. I would also urge the patient to inform all sexual partners so they can also seek treatment if needed. I would also instruct the patient to avoid all risk factors for STDs. Finally, I would ask the patient if they have any questions. 2. ORCHITIS A young male patient has just been diagnosed with orchitis.

The physician requests you provide the patient with the printed information concerning this condition. How do you approach this patient-teaching opportunity? ? First, I would sit down with the patient and read the printed instructions to the patient. I would emphasize the importance of finishing the entire coarse of antibiotics. Suggest comfort measures, such as scrotal support and the use of ice packs. Explain the importance of follow-up appointments for urologic care. Finally, I would ask the patient if they have any questions. 3.

PREMENSTRUAL SYNDROME (PMS) A female patient complains of typical premenstrual syndrome symptoms. The office has printed information for patient teaching about this condition. The physician requests you to provide the information sheets to the patient and review them with her. How do you approach this patient-teaching opportunity? First, I would sit down with the patient and read the printed instructions to the patient. Inform the patient that women benefit from stress-reduction program or counseling to better cope with the symptoms.

Assure th patient that 50% of menstruating women experience PMS in some form. Finally, ask the patient if they have any questions. 4. ENDOMETRIOSIS A young female patient has been complaining of intolerable menstrual cramps and other pelvic pain. The diagnosis of endometriosis has been made. The physician has written instructions for this condition. You are instructed to provide the patient with the printed material and review it with her. How do you approach this patient-teaching opportunity? ? First, I would sit down with the patient and read the printed instructions to the patient.

I would review with the patient the issues surrounding the disease and that it can progress or even regress over time. Discuss treatment options such as: hormonal contraception or surgery. Also have the patient take and finish the prescribed medication. Finally, I would ask the patient if they have any questions. 5. PREECLAMPSIA (TOXEMIA) A pregnant patient has been experiencing elevated blood pressure and sudden weight gain. She has been diagnosed with preeclampsia. The physician has printed instructions for this condition.

You are instructed to provide this information to the patient and her family. How do you approach this patient-teaching opportunity? I would teach the patient of early and regular prenatal care to monitor weight, blood pressure, and urinalysis. If the patient is pregnant and is considered at risk for eclampsia, teach the warning signs to report: sudden weight gain, edema, headache, and increased blood pressure. Early signs can be managed to help prevent hospitalization and the onset of complications. Finally, I would ask the patient if they have any questions.

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Pathogenic Parasite and Waterborne Diseases in Three Stations

Chapter 1 INTRODUCTION Background of the Study Rivers are the bodies of water bearing an immense biological importance. Though they contain only about 0. 0001% of the total amount of water in the world at any given time, rivers are vital carriers of water and nutrients to areas all around the earth, they are essential components of the hydrological cycle, for they act as drainage channels for surface water and they serve as habitat for various organisms (Hebert, 2011). With rapid increase of the country’s population and urbanization, bodies of water tremendously began to be polluted.

This event commenced the contamination of drinking water as well as the widespread occurrence of waterborne diseases. Waterborne diseases are often caused by parasites which are directly transmitted through consuming contaminated drinking water. Any water reserve, infested with pathogenic parasites, used in the preparation of food can be considered as a source of foodborne disease and could be easily transmitted through consumption of the same pathogenic parasites. These diseases commonly affect the digestive tract as well as the other vital parts of the body that may be fatal to anyone especially those who are immunocompromised (WHO, 2004).

Globally, waterborne diseases such as diarrhea accounts for 1. 5 million deaths annually according to the Centers for Disease Control and Prevention on its report in 2010. It is considered one of the most dangerous diseases that could be acquired in flowing water and is a major health problem for developing countries. Also, according to World Health Organization (WHO) on its report in 2004, diarrheal disease accounts for an estimated 4. 1% of the total Disability-adjusted Life Year (DALY) global burden of disease and is responsible for the deaths of 1. million people every year. It was estimated that 88% of that burden is attributable to unsafe water supply, sanitation and hygiene, and is mostly concentrated in children in developing countries. Over the time – from 2004 up to the present – , rapid increase in population, urbanization, and industrialization reduce the quality of Philippine waters, especially in densely populated areas and regions of industrial and agricultural activities. The discharge of domestic and industrial wastewater and agricultural runoff has caused extensive pollution of the receiving ater-bodies. This effluent is in the form of raw sewage, detergents, fertilizer, heavy metals, chemical products, oils, and even solid waste. Each of these pollutants has a different noxious effect that influences human livelihood and translates into economic costs. Access to clean and adequate water remains an acute seasonal problem in urban and coastal areas in the Philippines. The National Capital Region (Metro Manila), Central Luzon, Southern Tagalog, and Central Visayas are the four urban critical regions in terms of water quality and quantity.

The Government’s monitoring data indicates that just over a third or 36 percent of the country’s river systems are classified as sources of public water supply, up to 58 percent of groundwater sampled is contaminated with coliform and needs treatment, approximately 31 percent of illness monitored for a five-year period were caused by waterborne sources, and many areas are experiencing a shortage of water supply during the dry season. Nearly 2. 2 million metric tons of organic pollution are produced annually by domestic (48 percent), agricultural (37 percent), and industrial (15 percent) sectors.

In the four water-critical regions, water pollution is dominated by domestic and industrial sources. Untreated wastewater affects health by spreading disease-causing parasites, makes water unfit for drinking and recreational use, threatens biodiversity, and deteriorates overall quality of life. Known diseases caused by poor water include gastro-enteritis, diarrhea, typhoid, cholera, dysentery and hepatitis. The number of water-related health outbreaks including deaths reported in newspapers is going up.

However, awareness regarding the need for improved sanitation and water pollution control, reflected by the willingness-to-pay and connection to a sewerage system where they are easily available, is very low (Philippines: Environment Monitor, 2003; Greenpeace 2007). Davao City has been expanding and growing in terms of population, economy and industry. In this manner, more raw materials are being demanded by these different sectors and as a result destruction of the natural resources is inevitable. Davao river ranks number seven among the largest river basins in the Philippines.

This is largest of the city’s nine principal watersheds. The river is the main natural reservoir of the aquifer in the city’s jurisdiction. Its length is about 143 kilometers. It has received domestic and industrial wastewater. Since the sewage systems have not yet been fully developed, the garbage has been discharge into the river leading to a wide-scale contamination of Davao River (Pascua et. al. , 2011). At present, residents within Davao River unceasingly make use of the water for bathing and washing which may present various threats to them.

Some use the river for livelihood e. g. sand quarrying and fishing and for recreational activities. But they are blinded by the fact that they can be infected by pathogenic parasites that would eventually lead to waterborne diseases. This study aims to determine the level of pathogenic parasites in the water. Having everyone in the community know the specific parasites present in the selected stations of Davao River – Bankerohan, Bucana and Magallanes – would eventually lead to a more effective prevention and disease control among the residents of the community.

The goal of clean water for everyone has to be achieved in a growing population of a city. This study also aims to measure the level of waterborne diseases in Davao River. Through this study, we can help the people be oriented with the danger of using contaminated water from Davao River. Related Literature The importance of urban rivers and streams for urban ecology and quality of life in cities is an increasing concern worldwide. The present state of rivers is much dependent on the history and trends of the society in each country.

In many situations water quality is still unsatisfying. Restoration of urban rivers is challenging because of intensive land use, danger of flooding and impacts of human activities for water quality and for the ecology of rivers (Jormola, 2008). Today about 50% of the global population are living in urban areas, placing one-third of their inhabitants into slums, and creating huge challenges to their environment and sanitation. Poor sanitation, poor treatments of waste water, as well as catastrophic floods introduce pathogenic bacteria into rivers, infecting and killing many people.

The goal of clean water for everyone has to be achieved with a still growing human population and their rapid concentration in large cities, often megacities. How long introduced pathogens survive in rivers and what their niches are remain poorly known but essential to control waterborne diseases in megacities. Biofilms are often niches for various pathogens because they possess high resistances against environmental stress. They also facilitate gene transfers of antibiotic resistance genes which become an increasing health problem.

Beside biofilms, amoebae are carriers of pathogenic bacteria and niches for their survival (Abraham, 2011). The World Health Organization says that every year more than 3. 4 million people die as a result of water related diseases, making it the leading cause of disease and death around the world. Most of the victims are young children, the vast majority of whom die of illnesses caused by organisms that thrive in water sources contaminated by raw sewage (Berman, 2009). Waterborne Diseases Many illnesses, contaminants, and injuries can be water, sanitation, or hygiene-related.

Waterborne diseases are caused by organisms that are directly spread through water. Water-related illnesses can be acquired due to lack of water for good hygiene and lack of sanitation. It is important to know how these diseases and contaminants affect humans where they are found, and how to reduce the chance getting ill or suffering injury. This will allow individuals to make informed decisions about water, hygiene, and sanitation-related activities (CDC, 2012). Parasitic Organisms Parasites may be present in food or in water and can be identified as causes of waterborne illness.

They range in size, from tiny single-celled organisms to worms visible to the naked eye. Their lifecycle may also vary. While some parasites use a permanent host, others go through a series of developmental phases using different animal or human hosts. The illnesses they can cause range from mild discomfort to debilitating illness and possibly death (USDA, 2011). Parasites cause over 2 billion infections per year worldwide. In the immunocompromised host these infections generally represent reactivation of infection from donor or in the allograft recipient often long after the initial infection (Wiley, 2004).

Inland and coastal surface waters can be contaminated by human waterborne zoonotic enteropathogens such as Cryptosporidium parvum, Giardia lamblia, Encephalitozoon intestinalis, E. hellem and Enterocytozoon bieneusi (Graczyket et. al, 2008). The aquatic ecosystem harbors many kinds of organisms. Some of these organisms are parasitic protozoa such as Cryptosporidium spp. and Giardia spp. , which have recently been recognized as important causes of water and food-borne disease outbreaks associated with fecal contamination (Doron, 2000; Karanis et al. , 2006).

Cryptosporidium is a parasite commonly found in lakes and rivers, especially when the water is contaminated with sewage and animal wastes. There have been six major outbreaks of cryptosporidiosis in the United States as a result of contamination of drinking water. One major outbreak in Milwaukee in 1993 affected over 400,000 persons. Cryptosporidial infection can thus be transmitted from fecally contaminated food and water, from animal-person contact, and via person-person contact. The probability of transmission from just a small amount of contamination is fairly high, since a recent study has determined that the 50% infective dose of C. arvum is only 132 oocysts for healthy persons with no previous serological immunity to cryptosporidiosis (Hannahs, G. 1995). Cryptosporidium is very resistant to disinfection, and even a well-operated water treatment system cannot ensure that drinking water will be completely free of this parasite. Cryptosporidium has caused several large waterborne disease outbreaks of gastrointestinal illness, with symptoms that include diarrhea, nausea, and/or stomach cramps (Freedrinkingwater. com, 2009). Cryptosporidiosis, a common finding in pediatric patients hospitalized for diarrhea in urban Manila, Republic of the Philippines.

Urban areas, particularly in the developing countries, frequently experience severe overcrowding with concomitant diminished sanitation. This situation is conducive to the transmission of enteric pathogens. It would be reasonable to expect that cryptosporidium oocysts are readily passed from human-to-human, human-to-animal and animal-to-human hosts. In rural areas around the world, human cryptosporidiosis is putatively associated with close human-animal contact, as in the case of animal handlers and similar agricultural situations (Laxer, M. 2003).

Giardia lamblia is the protozoan parasite responsible for the disease Giardiasis. Symptoms of acute Giardiasis include diarrhea, nausea, weight loss, malabsorption, abdominal cramps, flatulence, and anemia. The mode of transmission of Giardia is through fecal to oral route or ingestion of cysts. A person can become infected after accidentally swallowing the parasite; but cannot become infected through contact with blood. You can become infected with Giardia lamblia if you swallow contaminated recreational water. Recreational water such as in swimming pools, hot tubs, jacuzzis, fountains, lakes, rivers, prings, ponds, or streams that can be contaminated with sewage or feces from humans or animals (Vdresearch. com, 2008). The prevalence of Giardia and Cryptosporidium among 3,456 diarrheic patients corrected from May 2004 to May 2005 in the Philippines was determined. Of 133 (3. 8%) positive samples, 69 (2. 0%) were positive for Giardia and 67 (1. 9%) for Cryptosporidium. Three samples had co-infection with Giardia and Cryptosporidium. Luzon had the highest positive samples (5. 0%) followed by Mindanao (4. 9%), then Visayas (2. 2%). Giardia was most prevalent in Mindanao (3. 6%) while Cryptosporidium was most prevalent in Luzon (3. %). The prevalence of Giardia (2. 0%) among pediatric patients (0-18 years) did not significantly differ from that (1. 9%) among adults (>18 years old). However, for Cryptosporidium, the prevalence (2. 9%) among pediatric patients was significantly higher compared to that (0. 2%) among adult patients. In the pediatric population, the highest percentage of patients with Giardia was the 5-9 year old age group, while that of Cryptosporidium was in the 0-4 year old group. The prevalence of Giardia, but not Cryptosporidium, was significantly higher in male than female adults (Natividad, F. 008). Amoebic dysentery (amoebiasis) which is the agent of Entamoeba histolytica is widely seen around the world. About 50 million people has become infected a year and eventually over 100,000 people lose their lives. Amoebiasis come into being in consequence of taken of quad-core mature cysts from water, foods, goods or hands by orally. E. histolytica trophozoites are placed into the colon mucosa and submucosa then forms a bloodymucus diarrhea table. It forms abscesses by moving through blood to liver, lungs, brain and other tissues (Kaya, O. 2011).

The infection is common in developing countries and predominantly affects individuals with poor socioeconomic conditions, nonhygienic practices, and malnutrition (Rivera, W. 1998). Related Studies Waterborne diseases are the most prevalent infectious diseases in the developing countries especially in new settlements along the river. Waterborne diseases occur worldwide, and outbreaks caused by the contamination of community water systems and accidental ingestion of recreational waters have the potential to cause disease in large numbers of consumers. Statistics on outbreaks linked to contaminated water have been vailable in the USA since 1920 (Craun 1986), and since 1971, the Centers for Disease Control (CDC), the US Environmental Protection Agency (USEPA), and the Council of State and Territorial Epidemiologists have maintained a collaborative surveillance system for collecting data pertaining to the occurrence and causes of outbreaks of waterborne disease (Barwick et al. 2000; Lee et al. 2002). In Europe during 1986–96, 277 outbreaks associated with drinking and recreational water were reported from 16 European countries (Kramer et al. 2001). At least 325 water-associated outbreaks of parasitic protozoan disease have been reported.

North American and European outbreaks accounted for 93% of all reports and nearly two-thirds of outbreaks occurred in North America. Over 30% of all outbreaks were documented from Europe, with the UK accounting for 24% of outbreaks, worldwide. Giardia duodenalis and Cryptosporidium parvum account for the majority of outbreaks (40. 6% and 165; 50. 8%, respectively), Entamoeba histolytica and Cyclospora cayetanensis have been the aetiological agents in nine (2. 8%) and six (1. 8%) outbreaks, respectively, while Toxoplasma gondii and Isospora belli have been responsible for three outbreaks each (0. %) and Blastocystis hominis for two outbreaks (0. 6%). Balantidium coli, the microsporidia, Acanthamoeba and Naegleria fowleri were responsible for one outbreak, each (0. 3%). Moreover, the occurrence of Giardia and Cryptosporidium (oo)cysts in recreational rivers from Malaysia was reported. It was carried out in water samples at two rivers, ‘Sungai Congkak’ and ‘Sungai Batu’, located in Selangor State. The occurrence of both Giardia lamblia and Cryptosporidium parvum (oo)cysts was higher in Sungai Congkak (50% or 15/30 and 10% or 3/30 respectively) than Sungai Batu (16% or 5/30 and 3. % or 1/30 respectively). The mean density of cysts/L was 0. 72 in Sungai Congkak and 0. 023 in Sungai Batu, and that of oocysts/L was 0. 023 in Sungai Congkak and 0. 0033 in Sungai Batu, showing that the occurrence of Giardia was higher and more frequent than Cryptosporidium in both rivers. On the other hand, the Giardia and Cryptosporidium (oo)cysts were more concentrated at the downstream station, followed by midstream and upstream stations which might be due to human factors where settlements and recreation areas were located around and between midstream and downstream stations.

Failure to meet basic human needs for water in China leads to waterborne diseases and preventable deaths, especially among children. The OECD Environmental Indicators in China report issued in July 2007 estimated 30,000 rural children die each year from diarrhea caused by polluted water (OECD, 2007). The World Health Organization reported an incidence of 108. 4 mortalities per 100,000 persons from diarrhea-related illness in China in 2002. In 2003, the National Statistics Office said diarrheal diseases ranked second among the top causes of morbidity in the Philippines with 615,692 cases recorded (World Bank, 2006).

Diarrhea is considered a major cause of morbidity, especially in developing countries. In the Philippines, it was the leading cause of morbidity for the years 2001 and 2003, and the second in 2002 (National Statistics Office, 2006). Common causes of diarrhea are infections due to protozoa. These causative agents are either foodborne or waterborne. Among enteric protozoa, Giardia lamblia (syn. G. intestinalis or G. duodenalis) and Cryptosporidium spp. are the most commonly reported causes of water-borne diarrhea outbreaks (Natividad et al,2008).

The protozoa G. lamblia was first reported in the Philippines in 1977 and since then has been identified as a common intestinal parasite. Studies done in Luzon, in various localities in the Visayas, and in the southern islands of Mindanao indicate wide distribution of Giardia in the Philippines. (Natividad et al, 2008). Stool examinations in the Philippines typically included the identification of the common etiologic agents of diarrheas such as G. lamblia and Cryptosporidium.

According to the most recent nationwide survey of Giardia and Cryptosporidium provides basic information on the prevalence of these enteric protozoa in the Philippines. (Buerano et al, 2008). The worsening water quality is related to incidence of waterborne diseases, and is likely to increase a negative impact of floods on human health. Example of this is an unusual flood that occurred in Marikina City, resulting in high mortality and morbidity rates due to gastroenteritis and other waterborne diseases (The Asian Disaster Preparedness Center, August 2008).

The pollution of the surface water in Agusan River could cause a variety of contagious diseases. Those diseases could outbreak through several routes such as: infection by parasites (such as schistosome), which inhabit in the water and drinking of and/or contact with the polluted water river that may cause dysentery and diarrhea (Lomboy, 2011). Instead of developing Davao River as an economic resource, it is currently being used as a central septic tank according to the Davao River Conservation Coordinating Committee.

A study conducted by the committee showed that about 11 drainage systems in the city are moving into the Davao River (Manila Bulletin Publishing Corp. , 2004). Currently, Davao River has become a dumping site for garbage, biological wastes, chemical wastes and other pollutants carried by the residents and even people just within the area (Pascua et. al. , 2011). Thus, areas near or within the urbanized populace such as Bankerohan, Magallanes and Bucana, are considered polluted and may be the source of detrimental effects to those who live nearby. Conceptual Framework

INDEPENDENT VARIABLEDEPENDENT VARIABLE Fig. 1 Conceptual Paradigm Showing the Relationship of Independent and Dependent Variables of the Study Presented in Fig. 1 above is the conceptual paradigm showing the independent variable, the pathogenic parasites and its levels on the three stations of Davao River namely Bankerohan, Magallanes and Bucana and is the subject of the study. The waterborne diseases and its levels would depend on what pathogenic parasites are found on the three stations of Davao River and is considered the dependent variable of the study.

Statement of the Problem This study specifically aims to answer the following questions: 1. What is the level of pathogenic parasites in the following stations of Davao River: 1. Bankerohan? 2. Magallanes? 3. Bucana? 2. Is there a significant difference among the levels of pathogenic parasites? 3. What is the level of waterborne diseases in the following stations of Davao River: 1. Bankerohan? 2. Magallanes? 3. Bucana? 4. Is there a significant difference among the levels of waterborne diseases? 5.

Is there a significant association between the level of pathogenic parasites and the level of waterborne diseases? Null Hypotheses 1. Hypothesis free 2. There is no significant difference among the levels of pathogenic parasites in the three stations of Davao River. 3. Hypothesis free 4. There is no significant difference among the levels of waterborne diseases in the three stations of Davao River. 5. There is no significant association between the level of pathogenic parasites and the level of waterborne diseases in the three stations of Davao River. Significance of the Study

The results of this study would provide advantages to various fields namely: Government – They would be able to implement policies and ordinances regarding proper waste management and the dos and don’ts regarding the use of water from the river. The affected residents within the area would be supported and information dissemination within the community would be implemented. Environmental Groups and Agencies – Having been aware on the situation of the 3 stations of Davao River, they would be able to provide solutions to lessen its contamination and prevent increase on water pollution.

Community – They would be given health awareness as well as the possible implementation of preventive measures and disease control. Teachers – This study would serve as an educational supplement and could be regarded as a learning material that could give additional knowledge to those who would desire to conduct a study related to pathogenic organisms found in urbanized rivers. Students – This study could serve as a reference material for further researches. Definition of Terms Davao River. It is one of the largest rivers in the Philippines and the largest in Davao Region.

It has a length of 143 kilometers. Salug River located in San Fernando, Bukidnon is its source and the mouth is located at the Davao Gulf. Bacteria. They are single-celled prokaryotic microscopic living organisms that could be pathogenic or likely to cause disease especially waterborne diseases since they could live in water and easily multiply. Parasite. It is an organism that lives in or on another organism (its host) and benefits by getting nutrients directly to its host. It is usually acquired through ingestion of contaminated food or water.

Waterborne disease. It is a disease acquired by drinking water contaminated at its source or in the distribution system, or by direct contact with environmental and recreational waters. It is a disease which results from infection with pathogenic microorganisms or chemical poisoning. Pathogenic microorganisms include viruses, bacteria, protozoans and helminthes. ———————– Waterborne diseases • Bucana • Magallanes • Bankerohan Pathogenic Parasites • Bucana • Magallanes • Bankerohan

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Latest Coral Disease

Coral disease is a disease found in coral that caused by an algae that grown in the reef tank. There are many identified coral diseases and its causes. One of which is white plague type II. White Plague Type II disease in corals is triggered by the direct contact of coral with macroalgae halimeda puntia. Nugues, claims that this disease causes the widespread death of corals that occur with heavy growth of macroalgae. Cited in Nugues. Et al; www.practicalfishing.co.uk. Macroalgae is said to be the responsible for many coral diseases that if not controlled, it will also lead to coral death. Other identified cause of coral disease is coral bleaching or white syndrome. With this disease, coral looked bleached which caused by the high sea temperature that led coral to eject the symbiotic algae that produce food for the coral.

Coral bleaching makes the coral weaker and more prone from attack of diseases. Extreme heat, due to global warming caused this coral bleaching because heat can trigger the virus in zooxanthellae, which is known for food production of corals. As the sea temperature becomes more heaters, more severe coral diseases are also expected to arise. This syndrome can treat and prevented if the sea temperature gets colder. Aside from warm temperature, overcrowding of corals also brings white syndrome. Researchers found out that the syndrome increases its rate from 1998, increased 20-fold in 2002, not just due to warm temperature but also because of overcrowding of corals. Researchers found out that corals can not breath and grow properly if they are closely tight with each other, and they are more prone to diseases. Widespread of disease easily occur if they are too close with each other.

There are also other five identified coral diseases and their causes aside from the diseases mention earlier. One is brown band. Dense population of single-celled organism called ciliates causes brown band. These ciliates are hairy organisms that eat the food of coral known as zooxanthellae, it appears as brown jelly that cause disease to corals. Second is black necrosing syndrome. Coral appears to be dead with this kind of disease. Black patches eat away the tissues of corals that leave in white skeleton. It is actually found out in many gorgonian corals in Northern Great Barrier Reef.

Third known disease is the pink spot. Pink spot is caused by the larval stage of the parasitic flatworm; which has three life stages that is parasitic on a mollusk, and affects the tissues of corals, which makes sensitive to predation by butterfly fish. However, healthy polyps regenerate from coral once the butterfly fish eats affected polyp. Fourth is Coral Tumor. These Tumors are formed by groups of polyps with increased growth rates. Corals affected with this disease appear to have spherical lumps raised about 4.5 cm from the surface of the coral. This tumor affects the reduction of function and growth of corals. There is a little known spread of numbers of this tumor and it is only monitored in Heron Island.

The fifth known disease of corals is black band disease. This disease is associated with cyanobacteria. Coral with black band disease looks healthy in front but dead and look white behind. This band can move across coral colony at rate of 44mm a day. Scientist first coral disease observed this disease last 1973. The sixth and last identified coral disease is the Skeletal Eroding Band. It is similar to black band disease. However, this disease produces a white skeleton speckled with empty black shells of the ciliate, which causes diseases that disrupt the process of secreting protective shells or loricae.

Work Cited:

Coral Diseases. www.altavista.com/coraldiseases

Latest Coral diseases. www.google.com

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The Argument on Obesity Being a Disease

Brad Ward English 152 Dr. Reiter 10/13/2011 The Argument on Obesity being a Disease Roughly, in the United States, there are 60 million people with the problem of obesity. Uniquely, this disease affects women in the United States more than men. Obesity is a problem because both men and women of all ages are exposed to a large amount of food in their everyday lives. He or she should lose weight because Obesity it can bring on a lot of health issues. This issue is a “big’’ problem in the U.

S and that issue is why some people say that they believe obesity is a disease and why another set of people that think a person chooses to live the lifestyle of obesity. One reason some people have problems with obesity is they live very convenient lives. “Does the family have clearly stated rules and are punishments logical consequences for rules that are broken (Kelly D. Brownell & John P. Foreyt)? ” Many people don’t have to exercise and do not eat healthily at all.

Most people take the easy way by taking elevators instead of climbing the stairs, or if they are hungry they go to a fast food restaurant instead of preparing a low fat meal at home. For example, in my family if nobody wants to cook, we usually go out and pick up something to eat, usually high calorie fast food. People today can also become so busy they don’t even attempt to exercise or eat health foods. The reason I know this is because I am busy almost every day. With school work, my job, and family duties I find little time for exercise or food preparation.

Eating healthily and staying fit is a lifestyle that everyone needs to switch over to so they can have more energy and also live longer. Most of the time it is not people’s choices that make them obese; it is either hereditary or a slow body metabolism. ‘’Obesity has become a highly contentious issue in part because the United States not only has one of the highest obesity rates in the world but has also led the industrial transformation of society to produce the ‘toxic environment’ now accepted by most governments as the problem” (WPT James S125). Obesity is so toxic that octors are finding obesity is liked with depression. ”We found that a self reported doctor diagnosis of depression was modestly associated with obesity, as well as significant genetic components to depression and obesity in female twins(Afari, Niloofar). ” Sometimes a certain gene in people’s bodies can cause them to be obese. For example, most of my family is big boned people. Some people have hypothyroidism or an underactive thyroid. This condition can make a person sluggish and out of energy so they will not be able to exercise or eat healthily.

With obesity, many restrictions follow, for example wearing certain sized clothing, or assigned particular seat on a bus, plane, or amusement park ride. If a person is obese they usually have a hard time to find clothes. For instance, most of time my dad goes to Shreveport to the Big & Tall men store. This is where he buys his shirts and pants at cheap price. This group of people feels that being obese is a lifestyle and that too much cost goes into providing the coverage for obesity.

But yet, people in the middle school system give Body /Mass index exams. “Doctors use the BMI mainly to categorize patients, into ‘overweight’ or ‘obese’, using either data from reference populations or drawing upon the U-shaped association between BMI and both, morbidity and mortality (Muller, M. J. ). ” So, why does the government not help do something for obesity? I believe that government is holding out on us and we can’t do anything about it unless we elect people that can fight on our behalf.

This is the one problem that gets to me because the government has the guts to sent all are jobs overseas but they are so skeptical about helping us as American to pay to “knockout” this obesity propbelm. Obesity can affect a lot of people’s health by causing diabetes, sleep disorders, heart complications, and breathing problems. For instance, a man named Joe who appeared on the TV show The Biggest Looser started the program weighing at 450 pounds and having to take medication for his health problems.

He stayed on the show for three weeks and he lost a whopping 215 pounds. Since he lost all of that weight he did have to take the medication anymore. If people worked on having the will power to exercise and eat healthily, they could have more energy and not feel exhausted. I know it is not always people’s fault for being obese but that does not mean they have to stay fat for the rest of their lives. All we need to is keep positive and Believe we can fight the better life.

If a person was to take their time and try it out they might get good results. Work cited (James, W. P. T. ). “WHO recognition of the global obesity epidemic. ” International Journal of Obesity 7 (2008): S125 (Kelly D. Brownell and John P. Foreyt). “Handbook of Eating Disorder” Basic Books, Inc. 513 (1986): 432 (Afari, Niloofar). ” Depression & Anxiety (1091-4269); Sep2010, Vol. 27 Issue 9, p799-806, 8p, 1 Diagram, 4 Charts (Muller, M. J. ). “Obesity Reviews; Aug2010, Vol. 11 Issue 8, p612-618, 7p, 2 Graphs

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Hemolytic Disease of the Newborn

Hemolytic Disease of the Newborn ————————————————- What is hemolytic disease of the newborn (HDN)? Hemolytic disease of the newborn is also called erythroblastosis fetalis. This condition occurs when there is an incompatibility between the blood types of the mother and baby. * “Hemolytic” means breaking down of red blood cells * “Erythroblastosis” refers to making of immature red blood cells * “Fetalis” refers to fetus ————————————————- What causes hemolytic disease of the newborn (HDN)?

HDN most frequently occurs when an Rh negative mother has a baby with an Rh positive father. When the baby’s Rh factor is positive, like the father’s, problems can develop if the baby’s red blood cells cross to the Rh negative mother. This usually happens at delivery when the placenta detaches. However, it may also happen anytime blood cells of the two circulations mix, such as during a miscarriage or abortion, with a fall, or during an invasive prenatal testing procedure (e. g. , an amniocentesis or chorionic villus sampling). The mother’s immune system sees the baby’s Rh positive red blood cells as “foreign. Just as when bacteria invade the body, the immune system responds by developing antibodies to fight and destroy these foreign cells. The mother’s immune system then keeps the antibodies in case the foreign cells appear again, even in a future pregnancy. The mother is now “Rh sensitized. ” In a first pregnancy, Rh sensitization is not likely. Usually, it only becomes a problem in a future pregnancy with another Rh positive baby. During that pregnancy, the mother’s antibodies cross the placenta to fight the Rh positive cells in the baby’s body.

As the antibodies destroy the red blood cells, the baby can become sick. This is called erythroblastosis fetalis during pregnancy. In the newborn, the condition is called hemolytic disease of the newborn. ————————————————- Who is affected by hemolytic disease of the newborn? Babies affected by HDN are usually in a mother’s second or higher pregnancy, after she has become sensitized with a first baby. HDN due to Rh incompatibility is about three times more likely in Caucasian babies than African-American babies. ———————————————— Why is hemolytic disease of the newborn a concern? When the mother’s antibodies attack the red blood cells, they are broken down and destroyed (hemolysis). This makes the baby anemic. Anemia is dangerous because it limits the ability of the blood to carry oxygen to the baby’s organs and tissues. As a result: * The baby’s body responds to the hemolysis by trying to make more red blood cells very quickly in the bone marrow and the liver and spleen. This causes these organs to get bigger.

The new red blood cells, called erythroblasts, are often immature and are not able to do the work of mature red blood cells. * As the red blood cells break down, a substance called bilirubin is formed. Babies are not easily able to get rid of the bilirubin and it can build up in the blood and other tissues and fluids of the baby’s body. This is called hyperbilirubinemia. Because bilirubin has a pigment or coloring, it causes a yellowing of the baby’s skin and tissues. This is called jaundice. Complications of hemolytic disease of the newborn can range from mild to severe.

The following are some of the problems that can result: During pregnancy: * Mild anemia, hyperbilirubinemia, and jaundice The placenta helps rid some of the bilirubin, but not all. * Severe anemia with enlargement of the liver and spleen  When these organs and the bone marrow cannot compensate for the fast destruction of red blood cells, severe anemia results and other organs are affected. * Hydrops fetalis This occurs as the baby’s organs are unable to handle the anemia. The heart begins to fail and large amounts of fluid build up in the baby’s tissues and organs.

A fetus with hydrops is at great risk of being stillborn. After birth: * Severe hyperbilirubinemia and jaundice The baby’s liver is unable to handle the large amount of bilirubin that results from red blood cell breakdown. The baby’s liver is enlarged and anemia continues. * Kernicterus Kernicterus is the most severe form of hyperbilirubinemia and results from the buildup of bilirubin in the brain. This can cause seizures, brain damage, deafness, and death. ————————————————- What are the symptoms of hemolytic disease of the newborn?

The following are the most common symptoms of hemolytic disease of the newborn. However, each baby may experience symptoms differently. During pregnancy symptoms may include: * With amniocentesis, the amniotic fluid may have a yellow coloring and contain bilirubin. * Ultrasound of the fetus shows enlarged liver, spleen, or heart and fluid buildup in the fetus’s abdomen. After birth, symptoms may include: * A pale coloring may be evident, due to anemia. * Jaundice, or yellow coloring of amniotic fluid, umbilical cord, skin, and eyes may be present.

The baby may not look yellow immediately after birth, but jaundice can develop quickly, usually within 24 to 36 hours. * The newborn may have an enlarged liver and spleen. * Babies with hydrops fetalis have severe edema (swelling) of the entire body and are extremely pale. They often have difficulty breathing. ————————————————- How is hemolytic disease of the newborn diagnosed? Because anemia, hyperbilirubinemia, and hydrops fetalis can occur with other diseases and conditions, the accurate diagnosis of HDN depends on determining if there is a blood group or blood type incompatibility.

Sometimes, the diagnosis can be made during pregnancy based on information from the following tests: * Testing for the presence of Rh positive antibodies in the mother’s blood * Ultrasound – to detect organ enlargement or fluid buildup in the fetus. Ultrasound is a diagnostic imaging technique which uses high-frequency sound waves and a computer to create images of blood vessels, tissues, and organs. Ultrasound is used to view internal organs as they function, and to assess blood flow through various vessels. * Amniocentesis – to measure the amount of bilirubin in the amniotic fluid.

Amniocentesis is a test performed to determine chromosomal and genetic disorders and certain birth defects. The test involves inserting a needle through the abdominal and uterine wall into the amniotic sac to retrieve a sample of amniotic fluid. * Sampling of some of the blood from the fetal umbilical cord during pregnancy to check for antibodies, bilirubin, and anemia in the fetus. Once a baby is born, diagnostic tests for HDN may include the following: * Testing of the baby’s umbilical cord blood for blood group, Rh factor, red blood cell count, and antibodies * Testing of the baby’s blood for bilirubin levels ———————————————— Treatment for hemolytic disease of the newborn Once HDN is diagnosed, treatment may be needed. Specific treatment for hemolytic disease of the newborn will be determined by your baby’s physician based on: * Your baby’s gestational age, overall health, and medical history * Extent of the disease * Your baby’s tolerance for specific medications, procedures, or therapies * Expectations for the course of the disease * Your opinion or preference During pregnancy, treatment for HDN may include: Intrauterine blood transfusion of red blood cells into the baby’s circulation  This is done by placing a needle through the mother’s uterus and into the abdominal cavity of the fetus or directly into the vein in the umbilical cord. It may be necessary to give a sedative medication to keep the baby from moving. Intrauterine transfusions may need to be repeated. * Early delivery if the fetus develops complications If the fetus has mature lungs, labor and delivery may be induced to prevent worsening of HDN. After birth, treatment may include: * Blood transfusions (for severe anemia) Intravenous fluids (for low blood pressure) * Help for respiratory distress using oxygen or a mechanical breathing machine * Exchange transfusion to replace the baby’s damaged blood with fresh blood  The exchange transfusion helps increase the red blood cell count and lower the levels of bilirubin. An exchange transfusion is done by alternating giving and withdrawing blood in small amounts through a vein or artery. Exchange transfusions may need to be repeated if the bilirubin levels remain high. ————————————————- Prevention of hemolytic disease of the newborn

Fortunately, HDN is a very preventable disease. Because of the advances in prenatal care, nearly all women with Rh negative blood are identified in early pregnancy by blood testing. If a mother is Rh negative and has not been sensitized, she is usually given a drug called Rh immunoglobulin (RhIg), also known as RhoGAM. This is a specially developed blood product that can prevent an Rh negative mother’s antibodies from being able to react to Rh positive cells. Many women are given RhoGAM around the 28th week of pregnancy. After the baby is born, a woman should receive a second dose of the drug within 72 hours.

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Lifestyle Diseases

Since the dawn of civilization, man’s physical attributes have always been in accordance with the work he was supposed to do. It has been proven that we were ape like before and had lots of body hair, which was then to protect us from cold. Eventually as time passed our physicality changed a lot, and we started to walk erect, but still we were built in such a way that we were fit for hunting and to endure other physical conditions. As centuries began to unfold, we started developing at a brisk pace and we have reached a stage of today, where we can get food by paying money for which we have to work, and that too doesn’t have to be necessarily a strenuous labor job. This change in lifestyle has brought about a lot of positivism and negativity in our lives.

Today we don’t have to strive for food nor fight wild animals, but today we have to work long hours, which how much ever tiring maybe aren’t strenuous to what we had to do earlier. This exact change has brought in the ‘lifestyle diseases’, which are responsible for maximum deaths in countries which are either developed or are in the brink of becoming developed. Today we have development in the field of medicine and the diseases of yester years are either extinct or they don’t possess a threat much. Since we don’t have much threat from infectious diseases as much as we had before, the life style diseases which mainly comprise of the following, affect us the most:

These diseases have been associated with the new way of life and come into the generic term of lifestyle diseases. Compared to the olden times, today obesity is a major problem which can be assessed by the following:

‘By 2001, almost 21 percent of adults were obese, representing a nearly 75 percent increase. Because these data are based on self-reported height and weight, obesity rates are most likely even higher than these estimates suggest. Results from the 1999 National Health and Nutrition Examination Survey, which collects data through clinical measurements, found that approximately 30 percent of U.S. adults are obese and an additional 34 percent are overweight and Even more alarming is the increase of those who are morbidly obese; that is, those who are 100 pounds or more overweight’ (Eileen Salinsky).

Obesity has been the root of many problems. Today children are always eating processed junk food and cola rather than salads and vegetables and milk. The pizzas and burgers how much ever scrumptious it is, cannot be considered as a main food and due to this reason not children but adults too tend to bloat up. An obese person is always at risk for heart diseases, diabetes and liver diseases. Being obese makes a person more inactive, this leads to other problems of muscles and joints. For obesity it is said that the more you eat the more you are eaten from inside. Today diseases like cancer have been one of the prime forces in eliminating mankind. There have been lots of deaths and amputations that have been accounted to cancer.

This diseases which was not much active in the olden times, is today’s prime diseases. Cancer has various forms, and if not it could have been prevented from maintaining a good staple diet. One thing that can be attributed from a lifestyle point of view is that in the west and developed countries, there has been a serious loss of staple food and required vegetables in the diet and there has been a major increase of meat and wine. Because of the use more technology cell phones have become a common thing amongst people, including teenagers, but one thing they do not know is using a cell phone over an hour increase the chances of having brain tumor as it emits high amount of radiation. Many people have contracted these tumors, but have failed to realize this that it was due to their lifestyle.

Heart Attacks and diabetes which also are lifestyle diseases are the worst in the group as they have killed more people than even one can imagine. The following will cement the fact about arteriosclerosis and diabetes: The WHO estimates that atherosclerosis (heart attacks and strokes) and diabetes (90% of the Type 2 variety) kill about 20 million people every year, more than are killed by war, famine, AIDS, tuberculosis and malaria combined, and more than might conceivably be killed in a single pandemic of bird flu. Bill Gates gives billions to trying to eliminate infectious disease but never mentions the really big killer, cardiovascular disease (CVD) in the form of atherosclerosis and hypertension or high blood pressure’ (Pandemic Lifestyle diseases 2007).

Life style diseases can be treated too, but it takes it toll on the individual, and for instances of heart and all major by pass operations have to performed, or for cancer chemotherapy or amputation of the part is required.

The best way is prevention of these diseases by changing our lifestyles. If we endorse certain amount of exercise and right amount of nutritious food then the chances of contracting these diseases go down by huge percentages. Fore mostly, it is very essential to keep a check on junk food and easy to make fried food. Apart from increasing cholesterol and obesity, these foods don’t help much. There has to be a steady intake of staple food with maintaining an equal balance of vegetables and meat. One has to make sure to complete a certain amount of exercise, be it a small run or doing exercises in the gym. This physical exercise will help increase the much needed blood circulation and in turn help people to live healthy.

The high amount of work loads only worsens the living environment, as tensions give rise to many diseases. Those working always on tight deadlines suffer the most from it. The only way to counter it is to take time out to relax and practice mind reliving techniques which can be attained via yoga or reiki. The lesser the tension the more an individual can live longer and enjoy life.  Alcohol and smoking, which are considered to be very normal in today’s times, are one of the worst ways of affecting our body.

Smoking contracts blood cells and can give lung cancer, along with dampening one’s stamina and appetite. Alcohol on the other hand makes one obese, addicted and also causes serious troubles in the liver and kidney region. If one can refrain from smoking and have very limited quantity of alcohol, then he reduces huge chances of getting diseases. The best part of lifestyle disease is it can be easily prevented with certain precautions. Everybody have to die in this world, but the choice of dying young due to lifestyle diseases or dying when you are old is a choice one has to make.

Works Cited:

1)   Eileen Salinsky, Principal Research Associate Wakina Scott, Research Associate “Obesity in America: A Growing Threat”, 11th July 2003, http://www.nhpf.org/pdfs_bp/BP_Obesity_7-03.pdf

2)  “Pandemic of Lifestyle Diseases”, 14th October 2007, http://www.panaceia-or-hygeia.com/

3)   http://naturalhealthperspective.com/home/civilization.html

4)  http://www.obesityinamerica.org/geographic.html

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Using Animals in Disease Research

Using Animals in Disease Research People all over the world have different opinions on whether animal testing is an ethical way to research drugs and treatments or not. Almost every medical advancement has involved using of animals including discovery of penicillin, organ transplantation, vaccines etc. Scientists should use animals in disease research because nowadays it is the only right way to develop drugs, treatments and cures for diseases and to be sure that new products are safe to use.

The first reason why animals should be used in lab testing is that it is the best way to do the research not on human beings but on something that is very similar to humans by chemistry, cell structure and organization. Only drug testing on animals will shows maximally closest result to what will happen in the human’s body. Perhaps we weren’t be able to cure even very common diseases in present-day medicine without using animals in researches. The second reason why scientists should use animals in their researches is that animal’s rights are still protected and they don’t feel pain during the testing.

According to Foundation for Biomedical Research, the Public Health Service Act, Federal laws, and Animal Welfare act controls the removal of pain. All animals used in procedures always relieved from pain by anesthesia. A well-treated animal provide more reliable scientific results, which is the goal of all researchers. The last reason why using animals in research is necessary is that human beings are more important than animals. Animals quickly reproduce itself and they have short life cycle that help scientists to study effects of the drugs on several generations. Also animals can be donors of organs for humans.

The society knows many facts in a last few years about transplanting of animal`s organs into human body. The opponents of using animals in disease research might say that scientists could discover drugs using alternative methods such as computer models. However, scientists should see the drug action in all system of living organism to be sure how it works. Using animals in lab testing and researches is necessary because alternative methods are currently not as reliable. Testing drugs and treatments on animals will someday help scientists find the cure for diseases like Alzheimer, AIDS, and cancer.

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Dutch Disease

(1. What is meant by the term? ) Introduction Over 50 years ago on 1960, when a sprawl bed of liquid gas was discovered in North Sea, Netherland overjoyed exploiting the natural resource and became a net exporter of gas. The demand for Dutch guilder in order to purchasing gas, rose and made it extremely strong. It left a lot of currency to a level the manufacturing export was no longer competitive. Later on 1970, when oil price soured by 4 times; UK was tempted to invest in North Sea oil industry in Scotland.

Soon after exporting the oil, UK encountered with a serious recession following labor strike. Firm workers demanded for higher wage because their disposal income has decreased which stemmed from the fall in expensive commodity demand. UK has become a net export of oil and Pound got appreciated. The rest of the industry left the market and firms started cutting their cost of human resources. Since then the term of “Dutch Disease” assign to those with heavy reliance on their supply of natural resources that downturn the non-resource aspect of economy.

The Export–oriented manufacturing system is divided to two parts; More competitive sector-normally energy sector- grow faster and further while the less competitive step back and the related employment fall substantially and in more serious crisis concludes to deindustrialization. Both mentioned event are correlated with exchange rate development. The term of “Dutch disease” for the first time came in an article in The Economist -1977 that described the case as a natural resource curse.

The name of Dutch Disease generally associated with a natural resource discovery, but it can be seen in any trade or investment activity that results in a large inflow of foreign currency, including a rise in natural resource prices, foreign aid, and foreign direct investment. The inflow of American treasures into Spain in 16th and gold discoveries in Australia in the 1850s are other two example of Dutch Disease diagnosis. By 1978, this story repeated in Iran. The oil price jumped and other local roduct like hand crafts, carpets, agricultural product, minerals, precious stones, Zofran, Pistachio became expensive and was not affordable for the neighbors and other importers to import. Such small industries never sustained in the market and some of them wiped out. Iran became the importer of rice, wheat, carpets. That took many jobs and money out of economy. Russia is likely to be another victim of this disease. Nearly 40% of GDP, 60% of export revenue and 60% of government revenue depends on oil and gas production. General perception of Russian economics, like other resource-rich countries, expects the symptom of disease.

Russia as one of the main oil producer can easily impact on oil price by reducing or increasing the amount of production. In both situations, their intake of money from oil exportation is huge. It strengthens the Ruble and impact the export revenue as a whole. Besides pouring unmanaged wealth problem, the direct investors intend to invest in mines and oil/gas wells and rigs or take over the related companies (direct investment). Moreover the related industry attracts the indirect investors to stock market to buy their shares.

These all concludes to CAD appreciation which is not what a commercial sector of an economy try to reach at. Since we are on another side of history, revolution against energy consumption and climate change got more serious, the countries that are too dependent on natural resource are being questioned more than before. Except for short-run effect of asymmetric growth on resource allocation and income distribution, we are better to think about long-run issue of not renewable resource depletion rate and future plan for rich-resource countries. 2. Detail and outline the channels that could cause such an effect) Dutch Disease Mechanism The underlying mechanism of the Dutch disease is that the real exchange rate of the resource- rich economy tends to appreciate strongly with the rise of the export revenues from the resource sector. In turn, the appreciation harms the economy’s exports from the manufacturing sector leading, over time, to de-industrialization . Regarding the pattern of history, the resource-rich countries manifest a short term prosper while others fallen behind due to: . Natural Resource discovery and exploitation 2. Increase in foreign currency 3. Foreign direct investment 4. Foreign aid 5. Natural resource price growth While at the mid-term they would experience: 1. Resource price artificially inflate the currency 2. Run up in commodity price 3. Losing price competition in market 4. Become weak in manufacturing sector 5. Become a net import of manufactured goods 6. Losing export power in goods other than natural resources 7. Leading to uneven economy

This is the mechanism in which non-resource industries get hurt by resource industry which proudly increases the wealth and spread the benefit unevenly across the country that accounts for hidden economy turmoil, which make manufacturing jobs, move to lower cost countries. Canada and Oil Sand Fever (3. Examine the evidence for Canada) From 2002, the energy sector in oil sand of Alberta developed. The total rise of world oil price covered all extra cost of oil sand refinery process and made it profitable to that level which triggered exploration, expansion, extraction and export of oil.

Obviously the nominal GDP per capita jumped and the Canadian exchange rate appreciated and the manufacturing sector has contracted. While the rise of the energy and commodity prices brings obvious benefits for Canada as a whole, it has raised also a lot of concerns of policy makers and economists. Tom Mulcair, the NDP leader, who is being accused of dividing the country against each other, named the oil sand of Canada the dirty oil. He said that the booming of oil industry in Saskatchewan province would hollow out other provinces’ economy.

He believes the oil exportation drive up the value of dollar and hurt manufacturing sector. The studies show that the appreciation of Canadian dollars relative to USD is driven by three factors. One of them is the strength of the CAD due to export oil, secondly the weakness of the USD, increase the appreciation of CAD, and the last factor is the booming of world energy price. Between 2002 to mid-2008 the price of oil and the other commodities got back to very low levels, however the manufacturing sector remained at the same weak status.

The Dutch phenomenon becomes a disease if the manufacturing sector does not come back when the resource boom is over. (4. Arguments for and against the preposition) Investigating the proposition that the country has experienced a period of Dutch disease, two conditions may need to be fulfilled. First, see if currency appreciation has driven up by the export oriented commodity prices. Second, see to what extend unemployment has been affected in the manufacturing sector. According to Krugman (1987), it becomes a disease when the manufacturing sector does not come back after the resource boom.

There are some contra verse arguments which claim that natural resource industries create jobs. Strong currency brings significant growth. While the food and energy security is so important in today’s world, there is no reason to blame these sectors for bad economy. Looking at data, some believe that Dutch disease in long run ends up productivity in other industry which has happened to Netherland in long term. (5. Government role to reduce the incident or mitigate the effect- foreign exchange intervention) “The gratification of wealth is not found in mere possession or in lavish expenditure, but in its wise application. – Miguel de Cervantes Saavedra Under transparently and wisely management, if government can diversify the manufacturing and export sectors to reduce dependency on the booming sector and make them less vulnerable to external shocks, such as a sudden drop in commodity prices and at the same time avoid dumping all export revenue in the economy and devote fund of energy revenue to enforce other part of the industry through privatization and restructuring, the economy would be more resilience and integrated.

In countries with temporary resource discovery, policymakers may want to protect the non-trade sectors through foreign exchange intervention that is, building up foreign exchange reserve through the sale of domestic currency to keep the foreign exchange value of the domestic currency lower to insulate the economy in condition the extra wealth spend wisely and to lead to inflation.

Nobody expect government to call for a slowing down of resource development, but it is expected that policymakers help to boost the innovation, investment in human resource and spend more on research and development which leads to higher productivity of skilled worker via retraining which should benefit the vulnerable sector. Developing the new energy infrastructural -pipe and rigs- intelligently and sustainably help peaking natural gas prices not being blamed for driving up inflation and driving down exports of manufacturing goods. In Russian, a few think that the national population must meets the domestic supply.

They claim that they are not that much depends on export revenue. Moreover they firmly believe that their non-oil industry is not that much big to get hurt from global competition and they would continue to develop the oil sector which is more competitive and they are good at. In Chad, after oil discovery on 2004, the Chadian government invested the income on developing crop production and feeding poor people at the same time. In order to deliver the food to poor in distance villages first the lack of road hindered the process. So the next object was to improve transportation infrastructural.

That was the example of successful policies for avoiding Dutch disease. Using the country’s huge income of oil and gas for public and rural household welfare and investing particularly in, for example, development of road and irrigation infrastructure and improving water access would adverse the affection of Dutch disease. “If revenue can create a serious opportunity for development and poverty reduction, it certainly is a good opportunity for corruption as well, feeding political claims and increasing the risk of conflict” (page 47) Exchange rate and Spending effect (6. ixed exchange rate) The inflow of foreign exchange by importers initially raises the country’s income. There are two policies how to spend the money. If the foreign currency is traded with foreign commodity and spend on import, the domestically product goods are remained unharmed. But suppose it is converted to local currency, this time the local productions get affected. If the central bank decided for a fixed nominal exchange rate, after conversion the currency, the money supply increases, the local demand increase and local production price rise which leads to higher real exchange rate.

If the exchange rate is flexible, the value of the domestic currency increases due to the increased supply of foreign currency, which again leads to higher real exchange rate, in this case through a rise in the nominal exchange rate rather than in domestic prices. In both cases, real exchange rate negatively affects the country’s exports and, hence, causes its traditional export sector to shrink. This entire process is called the “spending effect. ” •Corden, W. M. and J. P. Neary. 1982. Booming Sector and De-Industrialisation in a Small Open Economy.

The Economic Journal, 92 (368) pp. 825-848. •Coulombe, S. , R. Lamy and S. Rogers (2007). Adjustment in High Trade Exposed Manufacturing Employement in Canada, Industry Canada, Mimeo. •http://www. imf. org/external/pubs/ft/fandd/2003/03/ebra. htm •Ebrahim-zadeh, Christine (March 2003, Volume 40, Number 1). “Back to Basics – Dutch Disease: Too much wealth managed unwisely”. Finance and Development, A quarterly magazine of the IMF. IMF. •Corden and Neary . 1982. and Corden . 1984. •Stephanie Levy. 2001. “PUBLIC INVESTMENT TO REVERSE DUTCH DISEASE: THE CASE OF CHAD” •

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Lifestyle Disease

Definition of Lifestyle disease Lifestyle disease: A disease associated with the way a person or group of people lives. Lifestyle diseases include atherosclerosis, heart disease, and stroke; obesity and type 2 diabetes; and diseases associated with smoking and alcohol and drug abuse. Regular physical activity helps prevent obesity, heart disease, hypertension, diabetes, colon cancer, and premature mortality. ‘Lifestyle diseases’ such as heart disease, some cancers and diabetes, which are no longer a problem just in wealthy nations.

Globally 14. 2 million people between the ages of 30-69 years die prematurely each year from these diseases. These diseases have emerged as bigger killers than infectious or heridetary ones. Risk factors for these diseases include tobacco use, unhealthy diets and physical inactivity. Today we will take look at the most common lifestyle diseases that you need to take care. Some of the diseases which occur are due to the wrong lifestyle.

They are mainly due to the drugs, tobacco smoking and chewing, alcohol consumption, lack of physical activities, heavy junk food, over tension, no social life, lot of traveling, no specific eating habits and changes in eating hours, etc. It was observed that in many European countries in second half of the 20th century, people changed their food habits. They started consuming more and more meat, diary products, Alcoholic beverages; they had reduced the consumption of bread, potatoes, rice, and maize flour.

This reduced the intake of essential nutrients which were beneficial for the body at the same time they reduced doing physical exercises. This created an increase in ‘Cancer’ percentage amongst the masses. Due to large consumption of junk food and doing less exercises many started suffering from various heart aliments. Some of the common disorders and diseases amongst the masses due to wrong lifestyle are:- 1) Alzheimer’s 2) Asthma 3) Cancer 4) Type 2 diabetes 5) Heart disease 6) Chronic renal failure 7) Depression 8) Obesity

Lifestyle diseases are known as silent killers. Due to industrialization there was advancement in the life of the people according to that lifestyles changed, they started consuming junk food and did a very little physical activity. In the long run it started creating problems. Prior to 1940’s the main causes of deaths were Malaria, typhoid but after that due to changes in lifestyle more and more deaths occurred due to the Cancer, Heart attacks, Diabetes. Can we prevent these diseases? Yes, we can prevent those diseases by changing our lifestyle.

Following are the some important steps which can counter-attack the ill-effects of our wrong lifestyle: 1) Performing regular exercises. 2) Balance diet. 3) Reduction in unnecessary food consumption. 4) Avoiding junk food. 5) Proper eating times and habits. 6) Regularly doing yoga to refresh your mind and body. 7) Doing Meditation. 8) Sharing your thoughts with your friends Summary Wrong eating habits, less exercises, junk food are the main causes behind the deadly lifestyle diseases. More and more deaths are occurring due to this. Let’s change this and enjoy a healthy life.

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Biochemistry Fats, Diet, and Heart Disease

Biochemistry Fats, Diet, and Heart Disease ‘Fat’ can sometime be a word that gives people the chills when they hear about it. It is one of the three main sources of calories to our diet and a major part of ones dietary requirement. There are three kinds of fat: saturated, polyunsaturated and monounsaturated. The degree of saturation is dependent on the amount of double and triple bonds in the chemical makeup. Saturated fats are known to increase the body’s levels of serum (blood) cholesterol. Along with cholesterol, saturated fats can deposit on the inner walls of blood vessels; a condition known as atherosclerosis.

When the heart’s arteries become clogged with cholesterol and fats, blood flow can be restricted or totally blocked, leading to severe chest pain and heart attack. Polyunsaturated and monounsaturated fats actually have a cholesterol-lowering effect. By substituting polyunsaturated fats for the saturated fats in your diet, you can actually help control cholesterol levels. Too much dietary fat can also contribute to overweight. Being overweight can aggravate high blood pressure, place excess strain on your heart, and make it more difficult to stay active and physically fit, thus having a negative impact on your overall cardiovascular health.

For about three decades, health institutions like the American Heart Association, National Institutes of Health, World Health Organization, and others advised people to reduce dietary fat by limiting fat intake to fewer than 30 percent of daily calories. Their claim was that a low fat diet ultimately resulted in the reduction or elimination of risk for heart disease although; there wasn’t much evidence to support the notion of low-fat diets in the beginning.

In an article published in the Journal of the American Medical Association on February 8, 2006, in a 8th year Women’s Health Initiative Dietary Modification Trial, about 49,000 women with almost identical rates of heart attack, stroke, and other forms of cardiovascular disease were followed to see the effect of a low-fat diet and those not on the diet. Their results showed that women on the low-fat diet didn’t lose or gain any more weight than women who followed their usual diets. The important thing to note from these kinds of studies was the type of fat in the diet.

For example the Mediterrean style diet is high in fat but these fats are from plant sources such as olive oil, nuts and seeds which are low in saturated fat intake. The ‘Western” diet on the other hand has fats from animal sources which are usually saturated and produces a higher risk for heart disease. In conclusion, as research grows on diet and heart disease, it’s becoming clearer that looking at a single nutrient in isolation cannot tell us the whole story about a person’s heart disease risk. People eat foods, not nutrients, and they eat them in an overall dietary pattern.

The traditional Mediterranean Diet pattern, in contrast, appears to lower the risk of heart disease, stroke, and metabolic syndrome, a constellation of factors that increases the chances of developing heart disease and diabetes. So if you are concerned about heart health, pay attention to your overall diet, not just to the type of fat. Citation Barbara, H. (2006) et al. Low-fat dietary pattern and risk of cardiovascular disease. Journal of the American Medical Association. Retrieved from http://jama. ama-assn. org/content/29 5/6/655. full

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Kawasaki Disease

Acknowledgement This case study would not be possible without the guidance and the help of several individuals who are in one way or another contributed and extended their valuable assistance in the preparation and completion of this study. My outmost gratitude to Ms. Maria Donna Duron, the school directress of St. Augustine School of Nursing Espana for her genuine sincerity and encouragement. To my adviser Ms. Cecilia J. Sarte for her patiently supervising and assisting us with their knowledge, as we gradually go through the process of doing the case study itself, sincerest thanks. To my clinical instructor Mr.

Joey M. Cadano for all the help and valuable insight he had shared To my instructor Mr. Paolo M. Zabat and all the faculty staff for their moral support and untiring effort in encouraging us to finish our study. To my classmates and friends who gave their moral support and help all the way despite the busy schedules in preparing their own case study. To my family for supporting me all the way, providing me with everything I need financially and emotionally. Last but not the least, to our Almighty Father for his unceasing guidance and blessings, for constantly giving me hope, courage and patience.

Truly none of this is possible without you. ii Table of Contents TitlePage Number I. Acknowledgementii II. Objectiveiv III. Introduction a. Definition1 b. Incidence1 c. Etiology2 d. Manifestations and Complications2 IV. Anatomy and Physiology3 V. Pathophysiology6 VI. Patient’s Profile a. Biographical Data7 b. Chief Complaint7 c. History of Present Illness7 d. Medical History8 e. Family History8 VII. Laboratory Findings9 VIII. Physical Assessment11 IX. Nursing Care Plan15 X. Drug Study20 XI. Discharge Plan23 iii II. Objectives General:

The objective of my case study is to develop and acquire understanding, skills, and knowledge about the disease, and health promotion to prevent further complication on the condition of the patient. Specific: Nurse Centered ? Assess the patient’s overall health status ? Impart necessary health teachings to the patient ? Perform appropriate nursing care in conjunction with the condition of the patient ? Widen and enhance the student nurses’ knowledge and skills through additional research about the nature of the disease, its signs and symptoms, its pathophysiology, its diagnosis and treatment.

Patient Centered ? Know when to seek help from the health care providers whenever the signs and symptoms may appear ? Understand the occurrence of Kawasaki Disease ? Know what other complications may arise, if left untreated ? Gather information about the therapeutic regimen iv III. Introduction Definition Kawasaki Disease (mucocutaneous lymph node syndrome) is a form of vasculitis identified by an acute febrile illness with multiple systems affected. The cause is unknown, but autoimmunity, infection, and genetic predisposition are believed to be involved.

It affects mostly children between ages 3 months and 8 years; 80% are younger than age 5. It occurs more commonly in Japanese children or those of Japanese decent. It has seasonal epidemics, usually in late winter and early spring. It was first described in 1967 by Dr. Tomisaku Kawasaki in Japan. Kawasaki Disease mainly affects the blood vessels, including coronary arteries. Blood vessels throughout the body get inflamed, and the most serious that could happen is on the heart. If left untreated after 10 days, children may have a higher risk to develop heart problems.

Kawasaki Disease manifests in three phases: acute, subacute, and convalescent. The acute phase begins with the abrupt onset of high fever that is unresponsive to antibiotics and antipyretics. The child then develops the remaining diagnostic symptoms. During this stage the child is typically very irritable. The subacute phase begins with the resolution of the fever and lasts until all clinical signs of KD have disappeared. During this phase the child is at greatest risk for the development of coronary artery aneurysms. Echocardiograms are used to monitor myocardial and coronary artery status.

In the convalescent phase, all the clinical signs of KD have resolved, but the laboratory values have not returned to normal (6 to 8 weeks after onset). At the end of this stage the child has regained his or her usual temperament, energy and appetite. The cause of Kawasaki Disease is unknown, but it is thought to be immunologic abnormalities that include increased activation of helper T-cells and increased level of immune mediators and anti-bodies that destroy endothelial cells have been detected during the acute phase of the disease.

It has been hypothesized that some unknown antigen, possibly a common infectious agent, triggers the immune response in a genetically predisposed child. Incidence Epidemics of Kawasaki disease primarily occur in the late winter and spring, at 2- to 3-year intervals. Approximately 3000 children with Kawasaki disease are hospitalized annually in the United States. The approximate annual race-specific incidence per 100,000 children younger than 5 years is 32. 5 cases for Americans of Asian and Pacific Island descent, 16. 9 cases for non-Hispanic African Americans, 11. cases for Hispanics, and 9. 1 cases for whites. Although Kawasaki disease has been reported in children of all ethnic origins, it occurs most commonly in Asian children, especially those of Japanese descent. Rates are intermediate among blacks, Polynesians, and Filipinos and are lowest among whites. Manifestations and Complications Manifestations: ? Fever for at least 5 days ? Polymorphous rash ? Strawberry tongue ? Cervical lymphadenopathy Complications: ? Changes in the extremities ? Conjunctival infection ? Vasculitis IV. Anatomy and Physiology [pic]

Cardiovascular System Knowing the functions of the cardiovascular system and the parts of the body that are part of it is critical in understanding the physiology of the human body. With its complex pathways of veins, arteries, and capillaries, the cardiovascular system keeps life pumping through you. The heart, blood vessels, and blood help to transport vital nutrients throughout the body as well as remove metabolic waste. They also help to protect the body and regulate body temperature. The cardiovascular system consists of the heart, blood vessels, and blood.

This system has three main functions: ? Transport of nutrients, oxygen, and hormones to cells throughout the body and removal of metabolic wastes (carbon dioxide, nitrogenous wastes). ? Protection of the body by white blood cells, antibodies, and complement proteins that circulate in the blood and defend the body against foreign microbes and toxins. Clotting mechanisms are also present that protect the body from blood loss after injuries. ? Regulation of body temperature, fluid pH, and water content of cells. [pic] Lymphatic System

An important supplement to the cardiovascular system in helping to remove toxins from the body, the lymphatic system is also a crucial support of the immune system. Unlike blood, lymph only moves one way through your body, propelled by the action of nearby skeletal muscles. The lymph is pushed into the bloodstream for elimination. Appreciating the importance of the lymphatic system in filtering, recycling, and producing blood as well as filtering lymph, collecting excess fluids, and absorbing fat-soluble materials is necessary to the understanding of human physiology.

The lymphatic system consists of lymphatic vessels, a fluid called lymph, lymph nodes, the thymus, and the spleen. This system supplements and extends the cardiovascular system in the following ways: ? The lymphatic system collects excess fluids and plasma proteins from surrounding tissues (interstitial fluids) and returns them to the blood circulation. Because lymphatic capillaries are more porous than blood capillaries, they are able to collect fluids, plasma proteins, and blood cells that have escaped from the blood.

Within lymphatic vessels, this collected material forms a usually colorless fluid called lymph, which is transported to the right and left subclavian veins of the circulatory system. ? The lymphatic system absorbs lipids and fat-soluble materials from the digestive tract. ? The lymphatic system filters the lymph by destroying pathogens, inactivating toxins, and removing particulate matter. Lymph nodes, small bodies interspersed along lymphatic vessels, act as cleaning filters and as immune response centers that defend against infection. V.

Pathophysiology VI. Patient’s Profile Biographical Data Name: S. T. Age: 3 years old Gender:Male Address:Quezon City Birth date: January 14, 2010 Religion: Catholic Nationality:Filipino Informant: “Mother” Date of Admission:February 17, 2013 Admission Data Chief Complaint: “High Fever” Initial Diagnosis: Urinary Tract Infection Final Diagnosis: Kawasaki Disease Attending Physician: Dr. K. D. History of Present illness Patient’s present condition started 5 days prior to admission when patient have fever at 38. 5°C associated with rash from face to neck.

The patient was brought to Capitol Medical Center and diagnosed with UTI due to bacteria present in his urine. He was given paracetamol and antibiotics for the treatment. They allowed to go home. 4 days PTA, still with fever documented at 39. 5°C and rash. Swelling of face and lips are cracked. The mother noticed short, quick breathing. The patient was brought again to the hospital, strawberry tongue is noted upon physical examination. The patient was referred to Infectious Disease (ID) Specialist and confirmed having Kawasaki Disease upon conformatory and other laboratory finding.

Past Health History Patient’s mother verbalized that all needed immunizations since birth has been done to the patient. The patient has only experience stomach pain and minor health problems such as occasional cough, cold, and mild fever. Family History | |Mother |Father | |Hypertension |- |+ | |PTB – |- | |Cancer |- |- | |Allergies |- |- | VII. Laboratory Findings Urinalysis Report |Normal |Actual |Interpretations |Implication | |Color |Light or Pale yellow |Light Yellow |Normal |indicates good hydration and | | | | | |urine concen | | | | | |tration | |Character |Clear |Slightly Turbid |Abnormal |increase fluid intake | |Glucose |(-) |(-) |Normal |well hydrated | |Reaction |4. 6-8ph |6. ph |Normal |there is normal hydrogen ion | | | | | |concentration and extracellular| | | | | |fluid | | | | | | | | | | | | | | | | | | | |Specific Gravity |1. 010-1. 025 |1. 010 |Normal |the concentrating ability of | | | | |the kidney is normal | | | | | | | | | | | | | | | | | | | |PUS cell |0 |5-8 |Abnormal |indicates possible urinary | | | | | |tract infection | | | | | |Administer antibiotic as | | | | | |ordered | | | | | | | | | | | | | | | | | | | |Squamous |(-) |Few |Abnormal |increase fluid intake | | | | | | | |Bacteria |(-) |Few |Abnormal |increase fluid intake | | | | | |increase intake of Vitamin C | | | | | | | | | | | | | | | | | | | Hematology Report Laboratory/ Diagnostic |Results |Normal Values |Interpretation |Implication | |Procedures | | | | | |Hemoglobin |106 g/L |130-180 |decrease |Decresed hemoglobin leads | | | | | |to symptoms of anemia | |Hematocrit |0. 32 % |0. 40-0. 54 |decrease |Decreased hematocrit leads| | | | | |to symptoms of anemia | |WBC Count |20. 07 |5. 0-10. |increase |Increased WBC was due to | | | | | |presence of infection | |Coagulation Profile | | | | | |Platelet Count |605 |150-450 |increase |Increased PLT points to | | | | | |abnormal conditions of | | | | | |excess clotting | |Differential Count | | | | | |Neutrophil |65 % |50-70 % |normal |Within normal condition | |Lymphocytes |45 % |25-35 % |increase |Will lead to signs of | | | | | |viral infection | |Eosinophil |1 % |1-5 % |normal |Within normal condition | VIII. Physical Assessment |AREA/ REGION |METHOD USED |NORMAL FINDINGS |ACTUAL |INTERPRETATION/ ANALYSIS | | | | |FINDINGS | | | | | | | | |General Appearance | |>Temp: 36. 5-37. 2°C |> Temp: 39. 5°C |Not normal.

All this symptoms are | | | | | |present due to hyperthermia with | | | |>Resp. Rate: 20-30 cpm | |manifestations of increased respiratory| | |Inspection | |> Resp. Rate: 35cpm |rate and cardiac rate. Fundamentals of | | | |>Pulse Rate: 80-130 cpm | |Nursing, Kozier & Erbs 8th Edition, | | | | |> Pulse Rate: |pp. 529. | |Auscultation |> No Pallor |140bpm | | | | | | | | | | |> Without signs of fatigue |> Pallor | | | |Inspection | | | | | | |> No edema |> Fatigue | | | | | | |Accumulation of fluid in the | | | | | |extremities because of prolong staying | | | | |> Bipedal non- pitting edema |in bed, and excessive accumulation of | | |Palpation | | |fluid in the third spaces, edema | | | | | |developed. Fundamentals of Nursing, | | | | | |Kozier & Erbs 8th Edition, pp. 579. | | | | | | | | | | | | | | | | |Not normal due to excessive | | | | | |accumulation of fluid in the third | | | | | |spaces, edema developed.

Fundamentals | | | |> No edema | |of Nursing, Kozier & Erbs 8th Edition, | | | | | |pp. 579. | | | | |> With non- pitting edema | | |Skin | | | | | | |Palpation | | | | | | | | |Not normal.

Temperature exceeds the | | | | | |normal temperature because of the | | | | | |presence of infection that causes the | | | | | |skin to be warm. | | | | | | | | | | | |Not normal.

A skin lesion is an | | | |> Skin is mildly warm to | |alteration in a client’s normal skin | | | |touch |> Warm to touch |appearance. Fundamentals of Nursing, | | | | | |Kozier & Erbs 8th Edition, pp. 576. | | | | | | | | | | | |Not normal. Poor capillary refill | | | | | |results in poor oxygenation. | | | | | | | | |> Without peeling, must be | | | | | |soft and smooth |> Peeling (desquamation) palms |Not normal because there is increase | | | | |and soles |inflammation of the blood vessels | | | | | |causing it to be red in color. | |Inspection | | | | | | | | | | | | | | | | | | |> Capillary refill is less | | | | | |than 3 seconds |> With a capillary refill of 5 | | | | | seconds | | | | | | |Normal | | | |> No infection, swelling and| | | | |Palpation |moist lips | | | | | | |> Red mucous membranes in the | | | | | |mouth |Normal | | | | | | | |Mouth | | |> Dry lips | | | |Inspection | | | | | | | |> Cracked lips |Not normal due to infection. | | | | | |Fundamentals of Nursing, Kozier & Erbs | | | | |> Strawberry tongue noted |8th Edition, pp. 607 | | | |> Reactive/ responsive to | | | | | |noises |> Reacts to loud noises |Not normal.

Use of accessory muscle | | | | | |(abdominal muscle, trapezius muscle, | | | |> Symmetrical and patent | |and sternocleidomastoid muscle) and | | | | |> Symmetrical and patent |increased RR signifies fatigue and | | | | | |hyperthermia. | |Ears | |> Not palpable | |Fundamentals of Nursing, Kozier & Erbs | | | | |> Enlarged, palpable |8th Edition, pp. 548. | | | | | | | | | | | | |Nose | | | | | | |Inspection |> Breath sounds are resonant|>Breath sounds are resonant | | | | | | | | | | | |> Thorax is rounded | | |Lymph Nodes | |> thorax is rounded | | | | |Inspection | | | | | |Palpation |>normal RR 20-30cpm, |> RR 35cpm |> Not normal due to inflammation of the| | | | | |skin lesions | | | |> normal PR 80-130bpm | | | |Chest, Thorax and Lungs | | |>HR 140bpm | | | |Percussion |> no use of accessory | | | | | |muscles in breathing. | | | | | | |> Use of accessory muscle | | | |Inspection | |(abdominal muscle, trapezius | | | | | |muscle, and sternocleidomastoid |> Not normal due to process of the | | | |> Unblemished skin |muscle) |disease and infection.

Weakness is due | | |Palpation | | |to lack of energy needed to do normal | | | |> No tenderness; relaxed |> Presence of rash |activities. | | | |abdomen with smooth, | | | | | |consistent tension | |Not normal. Pain was caused by the | | | | |> Tenderness and |presence of bacteria in the urine. | | |> No restriction in |hypersensitivity | | | |Inspection |activities, no weakness and | | | | |Auscultation |alert | | | | | | | | | | | | | | | | | | |> Inability to tolerate | | |Abdomen | |> There should no pain felt |activities, weak in appearance, | | | | |when voiding |irritable and lethargic | | | |Inspection | | | | | |> Protein is not evident in | | | | | |the urine | | | | |Palpation | |> With difficulty in urination. | | | | | |Color of the urine is yellow | | | | |> Normal urine output is | |Not normal.

This is also caused by | | | |500-1000cc/day or equivalent| |accumulation of excessive fluid in the | |Musculoskeletal and | |to 20-25cc hr | |body | |neurolo- | | | | | |gical status |Inspection | | | | | | |> There should no edema, | | | | | |tenderness, or swelling | | | | | |present | | | | | | | |. |Genitourinary | | | | | | | | | | | | |Inspection | | | | | | | | | | | | | > Non-pitting edema on both feet| | | | | |noted | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |Lower Extremities | | | | | | | | | | | | |Inspection Palpation | | | | IX. Nursing Care Plan X. Drug Study XI. Discharge Plan Medication Patient is given discharge maintenance drug for 2 weeks of 120 mg of aspirin every day or 30 mg QID. Exercise/ Activity The patient can resume his usual activities as soon his condition become normal. There is no restriction with regard to physical activities as long as it is tolerable to the patient’s health status. Treatment Allow the child to rest for faster recovery. Since the patient is taking anti-platelet medications, precautionary measures are discussed to avoid bleeding tendency.

The patient is instructed to return to his attending physician within one week after date discharge for a follow up consultation. He is also required to have CBC, platelet count and ESR during that visit. Health Teaching Good hygiene is encouraged. Soft toothbrush are recommended. Petroleum jelly can be applied to dry cracked lips. Use mild soap in cleaning the skin and a mild lotion can be applied to protect skin from drying and peeling. Instill artificial tears to sooth conjunctiva as instructed. Outpatient Orders Remind the family on their follow-up check-up with their physician. Maintain good and safe environment to evaluate the progress of the treatment.

Diet Soft or pureed diet is advised when the child’s oral mucosa is still inflamed. Cool liquids like ice chips and ice pops can also be offered. Diet will return to usual when the child is able to tolerate it. Provide high protein diet to promote faster recover. Increase fluid intake to prevent dehydration. A Case Presentation of Kawasaki Disease In Partial Fulfilment of the requirement in Maternal and Child Nursing II A Compilation Presented to: St. Augustine School of Nursing Espana, Manila Presented By: Julie Anne G. Lumbera PN-4A Ms. Cecilia J. Sarte MCN II Instructor and Adviser Mr. Joey M. Cadano Clinical Instructor KAWASAKI DISEASE [pic]

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Cardiovascular Diseases

Cardiovascular disease Introduction Heart disease is No. 1 killer disease worldwide. It causes 12 million deaths annually. Thanks to the rising health awareness and government programmes this number significantly reduce during last 30 years. Coronary heart disease and cardiovascular disease Cardiovascular diseases are diseases of the heart (cardiac muscle?? ) or blood vessels (vasculature).

Cardiovascular disease (CVD) means all the diseases of the heart and circulation (blood vessels disease) including coronary heart disease (angina and heart attack) and stroke, as well as coronary and periphery blood vessels disease (problems with circulation). Diseases from this group are the biggest killer in Europe and USA, but developing and non-develop countries too. The final and most tragic consequence of different types of heart disease is heart attack with tragic consequences. Heart diseases are caused by atherosclerosis, a disease of arterial blood vessels resulted from atheroma i. . plaques accumulated (forming; sticking) on artery walls which makes the blood vessels nonelastic and narrowed and leads to decreased blood flow. For the atherosclerosis doctors very often use alternative name chronic cardiovascular disease. The opposite group acute heart disease made group of diseases which are dangerous for patients lives. Acute heart diseases include conditions or illnesses which usually have a rapid onset of symptoms and may resolve within days with or without treatment.

A condition or illness that is sudden or severe. On the other hand a condition or illness that arises slowly over days or weeks and may or may not resolve with treatment made a group of chronic heart disease. Both of them are caused by atheroma and the most known are next: a) Acute heart disease Heart attack is caused by lack of O2 in heart muscle cells. Very often it is caused by rupture of “hard plaques” patches which result in blood clots and partially or completely block blood flow and cause a heart attack.

When a fiber cap becomes thin, these “hard plaques” can suddenly rupture, spilling their contents, resulting in blood clots that partially or completely block blood flow and cause a heart attack http://www. authorstream. com/Presentation/nitin-35423-heart-diseases-science-technology-ppt-powerpoint/ Cholesterol glossary. http://www. mybwmc. org/library/28/000225 Stroke Stroke is death of brain cells caused by obstructed blood flow to parts of the brain. Since the level of LDL cholesterol is main cause of narrowed of blood vessels, it is necessary control it. If not treated properly, high LDL cholesterol can cause a stroke.

Cholesterol glossary. http://www. mybwmc. org/library/28/000225 b) Coronary heart disease Heart disease (coronary heart disease), When the plaque build up in th conorary arteries heart does not get sufficient blood, the condition is called coronary artery disease or coronary heart disease. Atherosclerosis is a disease of arterial blood vessels in which plaques form on artery walls. This is a consequence of different substances circulating in the bloodstream (inflammatory cells, proteins, cholesterol and calcium) sticking inside the vessel walls. Plaque patches influence on narrowing blood flow in the artery. ttp://www. bodybuilding. com/fun/gastelu5. htm Peripheral artery disease (reduced blood flow in the limbs, usually the legs Coronary plaque Coronary plaque is a term which use in practice as a synonym for atheroma or atherosclerosis. Patches of atheroma are formed from substances that circulate in the bloodstream. They consist of lipid, or fat, cores covered by collagen fiber caps which are sticking to the inside of the vessel walls. Over time plaque or patch of atheroma increases making an artery narrower and the blood flow through the artery is reducing.

We can see the changes in blood vessels caused by plaque in the Figure 1. Figure 1 Artery with the patches of atheroma – plaque Preventing Cardiovascular Diseases. Patient. co. uk. emis < www. patient. co. uk/health/Preventing-Cardiovascular-Diseases. htm> (March 13, 2013) http://medicineworld. org/blogs/heart/blog/permalinks/Jan-2006/coronary-plaque-detection-by-molecular-imaging. html> (March 13, 2013) Mature plaques typically consist of two main components: soft, lipid-rich atheromatous “gruel” and hard, collagen-rich sclerotic tissue.

Lipid-rich and soft plaques are more dangerous than collagen-rich and hard plaques because they are more unstable and rupture-prone and highly thrombogenic after disruption. Researchers have found that many people who have heart attacks do not have arteries narrowed by plaque. Many heart attacks are now known to be caused by soft or vulnerable plaques, located on an inflamed part of an artery. This plaque can burst, leading to the formation of a blood clot that can cause a heart attack. The 2009 issue of “The American Journal Pathology” edited explanation of those relations discovered by Olga Ovchinnikova and er colleagues. They found that inflammation results in the formation of soft (vulnerable) plaque which is filled with different cell types that promote blood clotting. This leads to a reduction of mature collagen, resulting in thinner caps that are more likely to rupture, even in the cases when total level of plaque isn’t extremely high. The authors advocate different viewpoints about relations between the plaque level and structure, i. e. its influence on heart attack. The first group claims that described types of blockages cause only about 30 percent of heart attacks.

On the other hand, some sources state that more than two-thirds of acute coronary events result from rupture of coronary plaques. However problems that plaque creates are extremely dangerous for people’s life and it is very important to prevent and monitor its appearance and changes. Graphs of vulnerable plaque and rupture of plaque which causes a heart attack is presented below. Figure 2 Vulnerable atherosclerotic plaques. Vulnerable atherosclerotic plaques. A. Atherosclerosis in a chronic disease that leads to plaque rupture and vascular occlusion. B.

Cross-section of a lethal coronary plaque rupture. Adapted from Heistad D. Unstable coronary-artery plaques. N Engl J Med. 2003. Atherosclerosis Modeling In-vitro. http://www. remedi. uzh. ch/research/disease. html Figure 3 Plaque Rupture and Heart attack http://hon. nucleusinc. com/generateexhibit. php? ID=30468&A=1027 Factors influencing plaque growth and stability Based on everything mentioned above and medical experience the conclusion about relations between heart attack and other cardiovascular disease and the level of plaque increasing are found.

The higher the level of plaque the higher risk of heart disease will be. The level of plaque will increase as the result of high level of cholesterol, type LDL, so called “bad cholesterol” in blood. When the level of LDL is normal, blood can pass in and out of the blood vessels without problems, but if it significantly increase particles of the blood will accumulate and sooner or later provoke trigger (cause) heart attack. Other very important factors influencing plaque level increasing are high blood pressure and cigarette smoking.

Both factors accelerate the plaque formation changing (damaging) artery walls and even more, helping cholesterol forming. Medical experience proved that plaque composition and vulnerability (hard or soft plaque) is more responsible for the conversion of a stable disease to a life-threatening condition than the plaque size. Except the plaque vulnerability the risk of plaque disruption is are consequence of rupture triggers (extrinsic forces). Soft plaque – lipid-rich one is more dangerous because of its instability and higher probability for rupture.

Even (IAKO) Although “hard plaque” that one having higher level of calcium influence on the blood vessels walls and their “hardness” experience show that heart attacks are mostly caused by soft plaque disruption. ??? Figure 4 Plaque rupture and its consequences in the form of heart diseases http://www. nature. com/nrg/journal/v7/n3/fig_tab/nrg1805_F2. html Risk factors of coronary heart disease Risk factors influencing cardiovascular disease we can group based on their stability into the three groups: a) Modifiable risk factors

In this group hypertension is the most dangerous risk factor for heart attacks, but even more for stroke. It is forming as the result of abnormal blood lipid levels which means high total cholesterol, high levels of triglycerides and high levels of low-density lipoprotein or low levels of high-density lipoprotein (HDL). Smoking, physical inactivity, Type 2 diabetes, and a diet full with saturated fats are risk factors strongly influencing the heart disease. All of them are treatable and patients (individuals) belonging into the different types of risk customers’ groups should avoid practice them. b) Non-modifiable risk factors

The factors from this group mostly are constant, like the case in gender or family history. Others are changing when time is passing, like age and lifestyle and personal habits. Older people have more chance to get heart attack and the man, especially those having “bad medical history”. Ration between man and woman are changing when women past the menopause. After that the level of risk is similar as the men’s one. As I’ve presented there is direct correlation between cardiovascular disease and condition and health of blood vessels, more precisely of developing atheroma, means level and structure of plaque in vessels.

On the other development of plaque and its level is directly influenced by level of cholesterol and some other elements which are connected with individual person and his/her life and genetic predispositions. As with the other diseases everybody has some risk of developing atheroma, but some risk factors increase the risk level for several categories. Those risk factors include: fn 12 •Fixed risk factors – factors that person cannot change: oA strong family history which means close relatives who developed heart disease or a stroke before they were 55 (for males) or 65 (for female). Severe baldness in men at the top of the head. oAn early menopause in women. oAge. Older people have more risk to develop atheroma. oEthnic group. Medical data show that people from different ethnic group have different risk for heart diseases. •Treatable or partly treatable risk factors include different health problems caused basically by the same causes as the: oHypertension (high blood pressure). oHigh cholesterol blood level. oHigh triglyceride (fat) blood level. oDiabetes. oKidney diseases causing diminished kidney function. All factors from this group have to be controlled and monitor.

Any kind of their complication probably will trigger more serious problems such as heart attack or stroke. •Lifestyle risk factors that can be prevented or changed. Actually these factors PRETHODE precede to those belonging to the second group. Except the genetic factors way of life and daily habits are the more responsible for different kind of heart diseases. Those factors are: oSmoking (Smoking cigarette increase blood pressure, decrease HDL; damages arteries and blood cells and increases heart attacks. Passive smoking is also a risk factor for cardiovascular disease ) oLack of physical activity. Obesity (People who are overweight (10-30% more than their normal body weight) have 2 to 6 times the risk of developing heart disease. ) oAn unhealthy diet and eating too much salt. oExcess alcohol. Looking on those three groups one can easily conclude that people with “bad predisposition” having high fixed risk factors have to think about their lifestyle risk factors even more, in order to try to decrease the second group of factors (treatable or partly treatable risk factors). On the other hand some of risks are more dangerous than the others; for example smoking increases risk for heart disease more than obesity.

And of course combination of two or more risk factors increases significantly the level of risks; older man (or woman) who smokes, without physical activity and with bad eating habits has more chance to get some of previously explained disease than the one who have “just one of bad habits”. The more risk factors someone has the greater is the likelihood that he/she will develop cardiovascular disease, unless taking action to modify his/her risk factors and working to prevent them compromising his/her heart health.

That doesn’t mean that people with “good genes” can be irresponsible and ZANEMARITI risk factors from other groups. With or without genetic predisposition modern life significantly increases a risk of heart disease for everybody. Hormones impact on lipids and other risk factors??? Different numbers of man and women died from heart attack initiated a lot of research about hormones’ influence on the risk factor and heart disease development. Number of men died from the heart attack outnumbered the number of women in pre-menopause period, but in the post-menopause data show completely opposite situation.

A percentage of women in post-menopause having heart disease and dying from heart attack increase dramatically and now outnumbered the men. ??? The main reasons for those changes are connected to the level of hormones and their influence on level and structure of cholesterol and consequently on risk factors and heart disease. As mentioned before total cholesterol actually is made of two different types of cholesterol: LDL – low density lipoprotein (LDL), so called bad cholesterol and high density lipoprotein (HDL).

High levels of LDL cholesterol lead to atherosclerosis increasing the risk of heart attack and ischemic stroke. HDL cholesterol reduces the risk of cardiovascular disease as it carries cholesterol away from the blood stream. http://www. walgreens. com/marketing/library/careguides/careguide. jsp? docid=000225=28=High%20Cholesterol Estrogen, a female hormone, raises HDL cholesterol levels, partially explaining the lower risk of cardiovascular disease seen in premenopausal women.

But after menopause (natural or surgical) when a level of estrogen significantly decreases total cholesterol rises, low density lipoprotein (LDL) cholesterol rises, and high density lipoprotein (HDL) cholesterol does not change or decreases slightly. This is the reason why negative hormones’ effect after menopause increasing more than proportionally. Some authors argue that even influence of estrogen on LDL and HDL level is proved it is yet unclear whether increase in risk is caused, at least partially, by increased level of androgen (the other of hormones belong to steroid as estrogen too), which is characteristics of menopause too.

This sexual dimorphism means a lower incidence in atherosclerotic diseases in premenopausal women, which subsequently rises in postmenopausal women to eventually equal that of men. These observations point towards estrogen and progesterone playing a lifetime protective role against CAD in women. As exogenous estrogen and estrogen plus progesterone preparations produce significant reductions in low-density lipoprotein (LDL) cholesterol levels and significant increases in high-density lipoprotein (HDL) cholesterol, this should in theory lower the risk of CAD.

UKLOPITI U ONO GORE Among estrogen’s positive effects on the heart are: •Reducing the LDL (“bad”) cholesterol in the blood. •Increasing the HDL (“good”) cholesterol in the blood. •Helping to keep blood vessels open. •Lowering blood pressure at night. •Reducing blood viscosity (how sticky the blood is), a property that may cause blood clots which could result in a heart attack or stroke. Estrogen’s effects on clotting are complicated, however, since there also is an increased risk for thromboembolism (a blood clot that blocks a vessel) in women taking estrogen. Possibly enhancing fibrinolysis, which is the body’s natural process for breaking down blood clots. Read more: http://ehealthmd. com/content/what-are-benefits-hrt#ixzz2NbWR3MxY http://ehealthmd. com/content/what-are-benefits-hrt#axzz2NbW1GJJN Nutrition guidelines As presented before three different groups of risk factor exist. Some of them people can change but the other are fixed, non-changeable because they caused by genetic heritage (??? ) influences. Controllable factors are connected to the lifestyle of person.

Lifestyle changes can prevent or slow the development of coronary plaque and heart disease. In order to prevent a disease development one have to keep track of his/her blood pressure and cholesterol levels. Choosing a heart-healthy diet is vital in controlling weight, which helps keep blood pressure and cholesterol levels down. Foods high in cholesterol and saturated fat should be avoided, and quitting smoking is imperative. Regular exercise and an increased overall activity level contribute to heart health and help reduce stress.

The risk of cardiovascular disease is possible to reduce following recommendation for lifestyle changing: Cessation of smoking and avoidance of second-hand smoke. Nutrition should ensure a healthy diet wiht total diet no more than 8% of saturated + trans fatty acids of total energy intake. All people, especially ones with high risk factors should lower alcohol consumption As the prevention physical activities are recommended – at least 30 minutes of moderate intensity physical activity per day or three days week (i. e. 150 mins/week minimum). ????

Currently practiced measures to prevent cardiovascular disease include: •A low-fat, high-fiber diet including whole grains and plenty of fresh fruit and vegetables (at least five portions a day)[29][30] •Tobacco cessation and avoidance of second-hand smoke;[29] •Limit alcohol consumption to the recommended daily limits;[29] consumption of 1-2 standard alcoholic drinks per day may reduce risk by 30%[31][32] However excessive alcohol intake increases the risk of cardiovascular disease. [33] •Lower blood pressures, if elevated, through the use of antihypertensive medications[citation needed]; •Decrease body fat (BMI) if overweight or obese;[34] Increase daily activity to 30 minutes of vigorous exercise per day at least five times per week;[29] •Decrease psychosocial stress. [35] Stress however plays a relatively minor role in hypertension. [36] Specific relaxation therapies are not supported by the evidence. [37] Routine counselling of adults to advise them to improve their diet and increase their physical activity has not been found to significantly alter behaviour, and thus is not recommended. [38] http://www. news-medical. net/health/What-is-Cardiovascular-Disease. aspx http://www. barnesandnoble. om/w/prevent-halt-and-reverse-heart-disease-joseph-piscatella/1100260037 Primary and secondary prevention of heart disease It is necessary start with prevention from heart disease as early as possible. Changes in the number of people killed by heart attack in developed countries show that prevention and awareness about this group of disease help to http://circ. ahajournals. org/content/123/20/2274/F2. expansion. html health plans must continue to drive cardiovascular care further along the continuum toward primary prevention of cardiovascular disease (CVD).

CVD risk factors should be managed not only after a coronary event has occurred, but also before the onset of such and event. Ideally, health lifestyles should be promoted with all patients so that risk factors for CVD never develop. In this way, CVD care can be moved from the inpatient setting to the outpatient setting. Sidney C. Smith Jr, MD. Focus on Cardiovascular Disease; A Word About the Quality of Care in Cardiovascular Disease. Director, Center for Cardiovascular Science and Medicine University of North Carolina at Chapel Hill. http://www. qualityprofiles. rg/leadership_series/cardiovascular_disease/cardiovascular_introduction. asp Key priorities for implementation Primary prevention of CVD •For the primary prevention of CVD in primary care, a systematic strategy should be used to identify people aged 40–74 who are likely to be at high risk •People should be prioritised on the basis of an estimate of their CVD risk before a full formal risk assessment. Their CVD risk should be estimated using CVD risk factors already recorded in primary care electronic medical records •Risk equations should be used to assess CVD risk People should be offered information about their absolute risk of CVD and about the absolute benefits and harms of an intervention over a 10-year period. This information should be in a form that: opresents individualised risk and benefit scenarios opresents the absolute risk of events numerically ouses appropriate diagrams and text (See www. npci. org. uk) •Before offering lipid modification therapy for primary prevention, all other modifiable CVD risk factors should be considered and their management optimised if possible.

Baseline blood tests and clinical assessment should be performed, and comorbidities and secondary causes of dyslipidaemia should be treated. Assessment should include: osmoking status oalcohol consumption oblood pressure (see ‘Hypertension’, NICE clinical guideline 34) obody mass index or other measure of obesity (see ‘Obesity’, NICE clinical guideline 43) ofasting total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides (if fasting levels are not already available) ofasting blood glucose orenal function oliver function (transaminases) thyroid-stimulating hormone (TSH) if dyslipidaemia is present •Statin therapy is recommended as part of the management strategy for the primary prevention of CVD for adults who have a 20% or greater 10-year risk of developing CVD. This level of risk should be estimated using an appropriate risk calculator, or by clinical assessment for people for whom an appropriate risk calculator is not available or appropriate (for example, older people, people with diabetes or people in high-risk ethnic groups) •Treatment for the primary prevention of CVD should be initiated with simvastatin 40 mg.

If there are potential drug interactions, or simvastatin 40 mg is contraindicated, a lower dose or alternative preparation such as pravastatin may be chosen. Secondary prevention of CVD •For secondary prevention, lipid modification therapy should be offered and should not be delayed by management of modifiable risk factors. Blood tests and clinical assessment should be performed, and comorbidities and secondary causes of dyslipidaemia should be treated.

Assessment should include: osmoking status oalcohol consumption oblood pressure (see ‘Hypertension’, NICE clinical guideline 34) obody mass index or other measure of obesity (see ‘Obesity’, NICE clinical guideline 43) ofasting total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides (if fasting levels are not already available) ofasting blood glucose orenal function oliver function (transaminases) othyroid-stimulating hormone (TSH) if dyslipidaemia is present. Statin therapy is recommended for adults with clinical evidence of CVD •People with acute coronary syndrome should be treated with a higher intensity statin. Any decision to offer a higher intensity statin should take into account the patient’s informed preference, comorbidities, multiple drug therapy, and the benefits and risks of treatment •Treatment for the secondary prevention of CVD should be initiated with simvastatin 40 mg. If there are potential drug interactions, or simvastatin 40 mg is contraindicated, a lower dose or alternative preparation such as pravastatin ay be chosen •In people taking statins for secondary prevention, consider increasing to simvastatin 80 mg or a drug of similar efficacy and acquisition cost if a total cholesterol of less than 4 mmol/litre or an LDL cholesterol of less than 2 mmol/litre is not attained. Any decision to offer a higher intensity statin should take into account informed preference, comorbidities, multiple drug therapy, and the benefit and risks of treatment http://www. eguidelines. co. uk/eguidelinesmain/guidelines/summaries/cardiovascular/nice_lipid_modification. php

How to lower the risk of cardiovascular disease The risk of cardiovascular disease is possible to reduce following recommendation for lifestyle changing: Cessation of smoking and avoidance of second-hand smoke. Nutrition should ensure a healthy diet wiht total diet no more than 8% of saturated + trans fatty acids of total energy intake. All people, especially ones with high risk factors should lower alcohol consumption As the prevention physical activities are recommended – at least 30 minutes of moderate intensity physical activity per day or three days week (i. . 150 mins/week minimum). Cessation of smoking The aim of this measure is complete cessation of smoking and avoidance of second-hand smoke. Patient and their families need to stop smoking. Those who are unable to quit may need professional help in form of counselling, behavioral therapy and even pharmacological therapy. Nicotine replacement therapy (NRT) is the first line choice of medication. Nutrition The aim of this measure is to ensure a healthy diet. Total diet should have no more than 8% (of total energy intake) of saturated + trans fatty acids.

All patients are advised to take approximately 1g Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) and more than 2g Alpha Linolenic Acid (ALA) daily. Diet should have vegetables, fruits and legumes, grain-based foods, moderate amounts of lean meats, poultry, fish and reduced fat dairy products. EPA and DHA can be obtained from oily fish and marine n-3 (fish oil) capsule supplements. Alcohol consumption All patients should be advised to lower alcohol consumption. Men should drink no more than 2 standard drinks per day and women no more than 1 standard drink per day. Physical activity

The aim of this measure is to raise physical activity and exercise to the recommended goal of at least 30 minutes of moderate intensity physical activity on most, if not all, days of the week (i. e. 150 mins/week minimum). Maintaining a healthy body weight The aim should be to achieve a waist measure of less than or equal to 94 cm in men and less than or equal to 80 cm in women. The body mass index (BMI) should be maintained at 18. 5–24. 9 kg/m2 Lowering blood cholesterol The aim of therapy should be to maintain blood cholesterol at: •Low density lipoprotein (LDL) at – less than 2. mmol/L •HDL – more than 1. 0 mmol/L •Triglyceride (TG) less than 1. 5 mmol/L The blood cholesterol can be maintained with the use of pharmacotherapy. Statins are commonly used lipid lowering drugs. Those with diabetes and atherosclerosis need stringent blood cholesterol control as well. Other lipid lowering drugs include fibrates like gemfibrosil, clofibrates etc, Ezetimiber and niacin. Lowering blood pressure High blood pressure is one of the important risk factors for cardiovascular disease. Those with coronary heart disease, diabetes, kidney disease or stroke need tight blood pressure control.

The aim should be a blood pressure of less than 130/80 mm of Hg. Diabetes and blood sugar control Those diagnosed with diabetes need stringent blood sugar control to prevent cardiovascular damage. HbA1c levels should be maintained at less than 7%. Other drugs to lower risk of cardiovascular disease Other drugs used to lower risk of cardiovascular diseases include: •Antiplatelet agents – this includes Aspirin and Clopidogrel. These drugs when given to patients with risk of heart attacks may prevent such attacks and events. •ACE inhibitors like Enalapril, Captopril, Lsinopril and

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Hauntington Disease

Huntington disease Name Institute Huntington Disease Introduction Shortage of information about Huntington disease (HD) and its non-clinical management inveigled me into a quest for journal articles about this comparatively rare illness. Having pored over scores of Journal of Clinical Nursing Issues, I stumbled across the article entitled “Exploring supportive care for individuals affected by Huntington disease and their family caregivers in a community setting”.

It immediately arrested my attention, as it touched upon the possible implications of HD for the affected persons, their family members (including those, who could inherit the illness genetically) and caregivers. This article is a collaborative work of the three authors from the University of Plymouth, namely Beverley Soltysiak, Penny Gardiner and Heather Skirton. It was published first on 10 July, 2008. Summary of the article

According to McDonald (2003), Huntington disease, formerly known as Huntington’s chorea, is a chronic neurodegenerative condition caused by a genetic mutation in the Huntingtin gene, situated on chromosome 4”. The article traverses implications and supportive care approaches to the individuals, who suffer from Huntington disease. Authors argue that different approaches should be applied to various age categories of the affected. The difference in symptoms may be subtle at first glance, but younger individuals, affected by the long-term conditions, find facilities for their senior counterparts unsuitable.

Important role in this regard belongs to the psychological aspects of the disease. People struck by HD tend to lead sedentary and recluse life. Huntington disease affects badly humans’ perception and cognition, renders their speech unintelligible, and makes them helpless to some extent in general. The far-reaching implications include unsteady gait and severe depressions, which sometimes result in strangers mistaking persons with HD for inebriates or drug abusers. It takes protracted periods of time and frenzied efforts of caregivers to jolt people ffected by Huntington disease out of the so-called “public alienation”. Authors argue that Huntington disease is debilitating in terms of its impact on the person’s physical condition, but they conclude that it is devouring person’s psychological strength even more eagerly. Sporadic outdoors activities lead to the development of the trait of standoffishness, which, in its turn, hinders the process of treatment. This illness is incurable, while affected people usually live no more than 30 years after the emergence of the first symptoms.

However, multifarious therapies and techniques aimed at helping patients to cope with the disease are employed (physiotherapy, occupational therapy, speech therapy). A multidisciplinary approach is utilized to make sure that complex care needs are met. Research focuses in part on interviewing the afflicted people in order to understand better how to help them to deal with the problems they face every day (anxiety disorders, animosity, petulance, apathy, and obsession). Depending on their willingness to cooperate, separate persons were interviewed individually or in groups.

It was found that participants with cognitive deficits or/and psychic disorders did not feel comfortable to communicate with impaired colleagues in groups, and consequently opted for individual interview or shunned it at all. The same specialists facilitated both group and individual interviews. “Data analysis was undertaken using inductive coding technique” (Miles & Huberman, 1994). Interviewers point out that it was a daunting task for them to conduct the research, because cognitive problems of people with Huntington disease barred interviewers from following their train of thought.

The heed was paid to the participants’ standpoint on the following themes: 1) Deciding whether to have genetic test; 2) Being given the lethal diagnosis; 3) Disclosure of information about the participant’s being diagnosed with HD; 4) Entering into serious relationship and having a child; 5) Making decisions about how to let children know of the genetic mutation; 6) Observing a family member suffer and wither from HD. Following the diagnosis of one individual, other family members are haunted by or preoccupied with the fear of having genetic mutation.

Some people prefer being oblivious to this possibility, while others, prompted by the desire to obtain confidence in future, eagerly agree to undergo a genetic test. In any event, propitious outcome of a genetic test has not proved to be a precondition for sunny disposition. It failed to provide them with a necessary degree of certainty, as those, who turned out to be healthy, started to monitor themselves vigilantly for the possible appearance of symptoms. Evaluation This article provides a comprehensive study of the implications of HD and the means to address the challenges that these implications entail.

The main emphasis is placed on those with HD; though, a good amount of attention is also paid to their family members, who are prone to inherit the genetic mutation, and caregivers. Bearing in mind brevity of this research and overall paucity of research into non-clinical management of HD, it would not be wise to grumble about certain details that authors failed to examine. However, I see it fit to note that more approaches of incorporating the afflicted people into the social milieu should have been developed, or at least, more thorough analysis of those listed should have been provided.

In terms of interest, I would give this article eight points out of ten. On the plus side, it is laced with excerpts from the interviews, which enable the readers to take a closer look at the problem. Moreover, authors managed to construe the material without abusing the buzzwords. This makes the article flow easily and renders it readable to a broad audience. Given the scarcity of knowledge about this area of health assessment, there are no slightest doubts that further research into this area should be carried out. Many gaps still are due to be filled. Some of the possible directions of research were mentioned above.

The information highlighted in this article would be of an utmost importance to the family members of people with HD and those, who take care of these people. Hospital staff could also defer to some advice put forward by Soltysiak et al. This article constitutes a precious groundwork for the researchers, who are interested in this particular area. Conclusion People affected by Huntington disease have to address a series of challenges in everyday life. It should be noted that neither these very people, nor their relatives, lead ordinary life after a family member has een diagnosed with HD. Huntington disease seriously undermines person’s physical and psychological well-being, with psychological effects having far greater scopes. Reluctance of the affected persons to engage in social activities exacerbated by their distorted vision of the world hampers the process of treatment. There is no efficient treatment at all; though, a number of therapies were developed to extenuate the implications. The problem is that at the same time as people with HD need outdoors activities to muster stamina, they also need to muster stamina to go outdoors.

By and large, individuals prone to HD feel frustrated at the lack of information about HD held by health professors. References MacDonald, M. E. , Gines, S. , Gusella, J. F. & Wheeler, V. C. (2003). Huntington’s disease. Neuromolecular Medicine, 4. Miles, M. , Huberman, A. (1994). Qualitative data analysis – an expanded sourcebook. (2nded. ). Thousand Oaks, CA: Sage Publications. Soltysiak, B. , Gardiner, P. , Skirton, H. (2008). Exploring supportive care for individuals affected by Huntington disease and their family caregivers in a community setting. Journal of Clinical Nursing, 17, 7b, 226-234.

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Stress, Dieting, and Periodontal Disease

Christine Dursunian Principles of Dental Hygiene II Professor Willis Research Paper Stress, dieting and periodontal disease and to compromised systemic health. Stress, dieting, cultural diversity, foundation of health and periodontal disease: The average person would never think that all four of these topics would coincide with one another. They do, each affecting the other as stepping stones towards periodontal disease. Periodontal disease, including periodontitis and gingivitis, are chronic, bacterial infections and inflammatory diseases affecting the periodontium (tissues that support the teeth).

Periodontal diseases are the most prevalent chronic diseases affecting children, adolescents, adults, and the elderly. The periodontium is a complex, highly specialized, shock-absorbing and pressure-sensing system consisting of four interrelated tissues supporting the teeth: cementum, periodontal ligament, alveolar bone and junctional and sulcular epithelia (1). Periodontal disease can affect one or many teeth. It can also lead to progressive bone loss around teeth, which can lead to loosening and possible loss of the teeth if left untreated.

There are many factors to periodontal disease that have been proven to be directly related to this growing disease, in certain populations and cultures that have been proven to stand out more than others. Through research and advanced studies with guidelines of evaluation, stress and dieting has been shown to be associated with periodontal disease(2). These additional factors involve diet, lifestyle, cultures, also including collective types of strains in ones everyday life. Periodontal disease is an infection of the tissues that support the teeth.

These infections are associated with specific pathogenic bacteria that colonize the subgingival area. When the teeth are being supported by the gingiva; the gingiva does not attach to the tooth firmly as one might think. Part of the tooth’s anatomy consists of a shallow v-shaped gaped called the sulcus which exists between the tooth and the gingiva. Periodontal disease affects this gap causing the tissue supporting the tooth to break down. Periodontal disease transitions through different levels to become what it is.

Research studies indicate that a specific set of guidelines during evaluation of the association of stress and periodontal disease are important. When proposing experimental approaches, specifically in psychosocial stress and periodontal disease; present studies and future experiments show the next six factors to be very useful. Periodontal disease is measured as unique disease outcome and should not be included in a composite index with other oral diseases(3). Validated instruments are assessed for stress, distress, and copying behaviors.

These helpful instruments, validated by prior studies, also on the population for each applied for research. Indications of compliance with oral health organization system should measure at-risk behaviors. Including oral health behaviors such as preventive dental visits, regulations of oral hygiene regimens, and an assessment of plaque, gingivitis, and other existing disease. By rigorously establishing psychosocial factors such as stress distress, and coping behaviors are true risk factors for periodontal disease case studies and case-control series generate hypotheses (4).

These hypotheses are over large cross-sectional and longitudinal epidemiological studies. Studies in which mechanisms of psychosocial stress or distress show the application of periodontal disease The necessity to show relationship and correlation of applying different assessments such as biochemical mediators of stress, immune functions, or neurological and endocrine alterations as well as behavioral changes are significant in these cases(5). Lastly are randomized controlled trial methodology, the intervention of studies using stress management to establish efficacy of modification of stress as modality of stress-associated disease.

Managing these controlled trials allows to reduce stress or distress. Periodontal disease has been associated for years with risk factors such as oral environment, age, female hormones, family factors, smoking and nicotine, and diseases associated with periodontal disease. When discussing oral environment the first issue that comes to mind is lack of oral hygiene. Lack of oral hygiene encourages bacterial buildup and plaque formation, which puts the oral cavity into a very susceptible position for periodontal disease.

Inadequate contoured restoration has also created rise to periodontal disease for its restorations of fillings and crowns. By poor dentistry the restorations help trap for debris and plaque because of its defect in contour. Anatomical tooth abnormalities are influential risk factors just as poor restorations would be, because of these abnormalities the teeth are not aligned in their natural state causing food particles to build up to the ladder of periodontal disease causing plaque and bacteria formation. Lastly would be the anatomy of the third molars, also known as the wisdom teeth.

This tooth especially is a known to be a major breeding ground for bacteria, by reason of its location and patients finding difficulty reaching posteriorly to the mouth while brushing. Other studies of this particular tooth show the unique tissues surrounding this molar region has been destructed of the plaque formation and the tissue becoming more sensitive when the third molar is impacted, meaning when the tooth is wedged between another tooth and the jaw. Next commonly associated risk factor with periodontal disease is age.

Another problem in aging, comes the increase of obtaining periodontal disease. Studies have shown that thirty percent of the adults in America have periodontal disease and mostly found in people over the age of seventy years old, eighty-six percent have periodontitis (6). Rare cases it has been shown for young adolescents who are subjected to this disease. Adding to this is family factors, periodontal disease often occurs to members of the same family. A mixture of factors belong to this title, such as intimacy, genetics and hygiene.

A considerably important factor is smoking and nicotine. Being the most significant factor, causing bone loss and gingival recession and inflammation by reducing the amount of oxygen present in the gingiva tissue. When nicotine combines with oral bacteria, the production levels expectations are greater. Lastly are diseases associated with periodontal disease, such as diabetes, type one and two, osteoporosis, herpes related gingivitis, human immunodeficiency virus associated with gingivitis, autoimmune disease (7).

Others diseases of genetic disorder are also at high risk for periodontitis. Contemporary conceptualization of the stress process supports the evaluation of stress at three levels. Stressors, moderating and mediating factors, and stress reactions. These three factors have emphasized the process and the unity stress can have on periodontal disease, including emotions and coping(8). These stress responses would be determined primarily by the process that makes personalized perception of a stress indicator or a threat to ones health.

The aim of each study is to unfold influential factors such as personality traits, coping strategies, and experimentation of referenced information (9). The resolution of all studies suggested that depression, stress, and salivary cortisol are important correlates of periodontal disease. Therefore, it is likely that periodontitis is related to immunologic and behavioral changes related to psychologic states. Salivary cortisol seemed to have different associations with periodontal disease, because of the outcomes in models involving stress compared to models involved with depression.

Periodontitis is indicated when addressing depression or stress. By strongly suggesting that stress, distress, and inadequate ways of handling difficult situations of coping are important risk indicators for periodontal disease. Furthermore, it is likely that systemic disease associated with periodontal disease such as diabetes, cardiovascular disease, preterm delivery and osteoporosis may share psychosocial stress as a common risk factor.

During these early beginnings of study and research, requirement for one to fully understand the molecular and cellular basis of the role of stress, and in turn these studies may lead to effective intervention strategies that minimize or negate stress as a contributor to periodontal disease. Research has also proven within certain limitations this systematic review showed a positive relationship between stress and psychosocial factors and periodontal disease.

However, caution should be used when interpreting this review because the different methodologies used in the included studies may have an impact on the results of the reports. The difficulties inherent is isolating the variable of stress, the lack of a reliable standardize  psychological analysis to quantify and define most psychiatric disturbances, the individual ability of patients to cope with negative life events, and the different types and clinical parameters used to determine periodontal tissue breakdown may cat as a confounding biases and cause result distortion at several stages. lthough a positive relationship was observed between stress and periodontal disease, further representative research is need to determine the impact of stress and psychological factors as risk factors for periodontal disease. Reference: Ng SKS, Leung WK. A community study on the relationship between stress, coping, affective dispositions and periodontal attachment loss. Community Dental Oral Epidemiol 2006; 24: 252-66 Page RC, Kornman KS. The pathogenesis of human periodontitis: an introduction. Periodontol 2000 1997; 14 9-11 Robert J. Genco, Alex W. Ho, Jeffrey Kopman, Sara G. Grossel, Robert G.

Dunford and Lisa A. Tedesco. Models to Evaluate the Role of Stress in Periodontal Disease. Department of Oral Biology, Periodontal Disease Research Center, School of Dental Medicine, State University of New York at Buffalo. Vol. 3, No 1, 288-302 July 1998. Amy E. Rosania, Kathryn G. Low, Cherly M. McCormick, and David A. Rosania. Stress, Depression, Cortisol, and Periodontal Disease. Department of Psychology, Bates College, Lewiston, ME. Volume 80, Number 2:260-266 February 2009. Breivik T, Thrane PS, Murison R, Gijermo P. Emotional stress effects on immunity, gingivitis, and periodontitis.

Eur J Oral Sci 1996; 104:327-334 Green LW, Tyron WW, Marks B, Juryun J. Periodontal disease as a function of life-events stress. J Human Stress 1986;12:32-6 Annsofi Johannsen, Gunnar Rylander, Birgitta Soder, and Marie Asberg. Dental Plaque, Gingival Inflammation, and Elevated Levels of Interleukin-6 and Cortisol in Gingival Crevicular Fluid From Women with stress-related Depression and Exhaustion. Volume 77 – November 8 2006; 77:1403-1409 Genco RJ, Ho AW, Grossi SG, Dunford RG, Tedesco LA. Relationship of stress distress and inadequate coping behaviors to periodontal disease.

J Periodontol 1999;70;711-23 Daiane C. Peruzzo, Bruno B. Benatti, Glaucia M. B. Ambrosano, Getullo R. Nogueria-Fiho, Enilson A. Sallum, Marcio Z. Casati, and Franciso H. Nociti Jr. A Systematic Review of Stress and Psychological Factors as Possible Risk Factors for Periodontal Disease. Volume 78- Number 8. 2007;78:1491-1504 Kaufman E, Lamster IB. Analysis of saliva for periodontal diagnosis- A review. J Clin Periodontal 2000; 27: 453-465 Arowojolu MO, Onyeaso CO, Dosumu EB, Idaboh GK. Effect on academic stress on periodontal health 2006;29:9-13