Research Topics: Health Condition

PNEUMONIA

PNEUMONIA   Introduction Pneumonia is an acute infection of the alveolar spaces of the lungs. The term includes any inflammatory condition of the lung in which some or all of the alveoli are filled with fluid and blood cells.             The patient experienced bacterial pneumonia. This is a common type of pneumonia, caused most frequently by pneumococci. This disease begins with infection in the alveoli; the pulmonary membrane becomes inflamed and highly porous so that fluid and even red and white blood cells leak out of the blood into the alveoli. Thus, the infected alveoli become progressively filled with fluid and cells, and the infection spreads by extension of bacteria from alveolus to alveolus. Eventually, large areas of the lungs, sometimes whole lobes or even a whole lung, become “consolidated,” which means that they are filled with fluid and cellular debris ( 2000).             The patient had a history of acute febrile illness associated with chill, chest pain and cough, especially with expectoration of viscid, rusty sputum which is practically diagnostic of pneumonia itself. The diagnosis is confirmed after physical examination of the patient discloses tachycardia, tachypnea, cyanosis, and signs of consolidation.   Cellular Pathophysiology             Pneumococci reach the lungs via the respiratory passages. They lodge in the alveoli, proliferate, and initiate an inflammatory process that begins with an outpouring of protein-rich fluid into the alveolar spaces. This fluid acts as a culture medium for the pneumococci and as a vehicle for their spread to other alveoli, segments (lobules), and lobes (1998).             Pathologically, the early stage of pneumonia (the first 12 to 48 hours) is called red hepatization because of the liver-like, reddish appearance of the consolidated lung that results from the characteristic widespread dilation of pulmonary blood vessels and the extravasation of erythrocytes into the alveoli ( 1998).             A few hours after the pulmonary capillaries dilate and the edema fluid pours into the alveoli, polymorphonuclear leukocytes enter the alveolar spaces, rapidly fill the alveoli, and consolidate the lung (grey hepatization). Surface phagocytosis occurs, without antibodies, by leukocytic trapping of the bacteria against an alveolar wall or another leukocyte; the process is more active when large numbers of leukocytes are present ( 1998). Tissue sections show few pneumococi in the consolidated lung, but many in the advancing margin of the lesion where edema fluid is abundant and leukocytes are sparse (1994).             The macrophage reaction occurs next, as large mononuclear cells enter the alveoli, engulf any remaining pneumococci, and phagocytized the cellular debris of the exudate. This process continues until resolution is complete, which is indicated by physical examination and x-ray evidence that the lungs are clear (1994).             The pathogenesis of other bacterial pneumonias resembles that of pneumococcal infections, but abscess formation may occur when infection is caused by organisms that destroy pulmonary tissue.   Systemic Pathophysiology             The patient who has pneumonia would experience a sudden, with a shaking chill, sharp pain in the involved hemothorax on the onset. Along with this are the appearance of cough with early sputum production, fever, and headache. All these symptoms are usually present as an effect of the cellular events that took place: red hepatization, grey hepatization, surface phagocytosis, and macrophage reaction.             All these cellular events lead to changes in the gas exchange functions of the lungs. In pneumonia, the gas exchange functions of the lungs change in different stages of the disease. In the early stages, the pneumonia process might well be localized to only one lung, with alveolar ventilation reduced while blood flow through the lung continues normally (2001). This results in two major pulmonary abnormalities: (1) reduction in the total available surface area of the respiratory membrane and (2) decreased ventilation-perfusion ratio. Both these effects cause hypoxemia (low blood oxygen) and hypercapnia (high blood carbon dioxide).             Human Pathophysiology             The effect of the resulting decreased ventilation-perfusion ratio in the patient with pneumonia is that the blood passing through the aerated lung becomes 97 per cent saturated with oxygen, whereas that passing through the unaerated lung is about 60 per cent saturated, causing the mean saturation of the blood in the left heart and in the aorta to be about 78 per cent, which is far below normal ( 2000).             Oxygen is one of the most necessary nutrients in the body. Whenever the availability of oxygen to the tissues decreases, such as in pneumonia, the blood flow through the tissues increases markedly.             Pneumococcal pneumonia is the most common bacterial pneumonia; many of its features are similar to those of pneumonia caused by other organisms. The disease is generally sporadic. Healthy carriers are usually responsible for the infection of others, but there is no practical way to identify carriers and eliminate the organisms (1998).   Credit:ivythesis.typepad.com

PNEUMONIA

PNEUMONIA Introduction Pneumonia is an acute infection of the alveolar spaces of the lungs. The term includes any inflammatory condi...

PROSTATE CANCER

PROSTATE CANCER   Prostate Cancer Incidence, Diagnosis and Staging               Cancer of the prostate gland is a common cause of death, accounting for about 2 to 3 percent of all male deaths (2000). Adenocarcinoma of the prostate accounts for the majority of malignancies in men over age 65. The etiology is unknown. Sarcoma of the prostate is rarely found in children. Undifferentiated prostatic carcinoma and squamous cell carcinoma of the prostate probably represent variants of adult adenocarcinoma and are less responsive to the usual measures of control.             Prostate cancer is also the most common cancer among men in the United Kingdom and the second most common cause of cancer-related deaths. In 1999, 20,842 new cases of prostate cancer were registered in the UK, giving a crude incidence rate of 75 cases per 100,000 men. Overall, 1 in 6 new cases of male cancers were prostate cancer and 9,491 men died from the disease. Prostate cancer accounts for 1 in 8 of all male cancer deaths (2002).             The usual prostatic malignancy is glandular, not unlike the histologic configuration of normal prostate. Frequent mitoses, stromal invasion, and involvement of perineural lymphatics constitute the principal histologic criteria of diagnosis.             Prostatic carcinoma is generally slowly progressive and may cause no symptoms. Late in the course of the disease, symptoms of bladder outlet obstruction, hematuria, and pyuria may appear. Matastases to the pelvis and lumbar spine may cause bone pain.             Stony hard induration of the prostate raises the suspicion of prostatic malignancy and must be distinguished from granulomatous prostatitis, prostatic tuberculosis, prostatic calculi, and other more unusual prostatic diseases. The firm and nodularly irregular prostate is pathognomonic of prostatic carcinoma, later exhibiting extension of induration and fixation of the gland to the rectum and the lateral pelvic walls.             There is a blood test for a protein called PSA, which can help to detect prostate cancer - but it needs to be used along with other tests to make a definite diagnosis. Prostatic carcinoma must be suspected on the basis of rectal findings. A solitary firm prostatic nodule should be biopsied immediately, preferably by open surgery to permit radical prostatectomy if indicated.             The more extensive processes may be defined by needle biopsy, either transrectally or transperineally. An elevated serum acid phosphatase indicates a large local tumor or metastases. Prostatic carcinoma produces osteoblastic bony metastases, and their radiographic demonstration in the presence of a stony hard prostate is diagnostic of cancer. Aspiration of bone marrow and demonstration of prostatic cellular configuration in metastatic cells confirm a diagnosis of incurable disease.   Risk Factors Associated with Prostate Cancer   Many men are unaware they even have prostate cancer, it develops from cells within the prostate gland but it is usually very slow growing. However, in some cases, it may grow more quickly and spread to other parts of the body. Age is a risk factor – as it is rare to find prostate cancer in men under 50 (2002). About 9 per cent of prostate cancer cases are diagnosed in men in their 50s, 30 per cent in men in their 60s and 40 per cent in men in their 70s. But having an elderly relative with prostate cancer is not uncommon and does not increase a person’s own risk.             Three risk factors for prostate cancer are associated with an increased likelihood of developing aggressive prostate cancer or dying of the disease. People with high levels of the acid-labile subunit (ALS) glycoprotein that regulates the bioavailability of the hormone insulin-like growth factor 1 (IGF-1) may have an increased risk for prostate cancer and its aggressive forms. Low plasma levels of vitamin D appear to significantly increase the risk of aggressive prostate cancer, especially in patients with a particular polymorphism of the vitamin D receptor (2005). The major risks are increasing age, especially past 50, a family history of the cancer, having a high-fat refined ‘Westernised’ diet and being of African or African-Caribbean origin (2006). Knowing more about the risks won’t stop a person from getting prostate cancer, but it will increase their chances of spotting it as early as possible and getting it successfully treated.   Treatment Options – with reference to available guidelines               Once cancer of the prostate gland does occur, the cancerous cells are usually stimulated to more rapid growth by testosterone and are inhibited by removal of both testes so that testosterone cannot be formed ( 2000). Also, prostatic cancer can be usually can be inhibited by administration of estrogens.             Early and localized prostatic carcinoma may be cured by radical perineal or retropubic prostatectomy. Extensive local disease or metastases may preclude surgical cure, in which case diagnostic confirmation should be followed by hormonal control, irradiation, or both. The treatment of choice is bilateral orchiectomy accompanied by estrogens.             Failure to respond to the hormone, or reactivation of disease, may be controlled with bilateral surgical adrenalectomy or “medical adrenalectomy.” Irradiation may provide prompt relief of pain from bony metastases refractory to other treatment and may be efficacious in control of local disease as well; long-term regression and possible cure of prostatic carcinoma have been observed in some cases treated by radiotherapy.             Even some patients who have prostatic cancer that has already metastasized to almost all bones of the body can be successfully treated for a few months to years bye removal of the testes, by estrogen therapy, or both; after this therapy the metastases usually diminish in size and the bones partially heal (2000). This treatment does not stop the cancer but does slow it and sometimes greatly diminishes the severe bone pain.   External Beam Radiotherapy Technique               Radiotherapy is the treatment of disease with radiation, especially by selective irradiation with x-rays or other ionizing radiation and by ingestion of radioisotopes. It is also called as radiation therapy. Long-term control of prostate cancer can be achieved in a relatively high-risk patient population using interstitial brachytherapy in combination with external beam radiation therapy (2003). External beam radiation has proven successful in the treatment of localized prostate cancer and is associated with a success rate comparable to surgery for patients with localized prostate cancer. The survival rate for patients with localized prostate cancer, stages A and B, treated with external beam radiation is similar to that for age-adjusted cohorts without prostate cancer (1996). External radiation generally is delivered in a daily dose of 180 cGy to 200 cGy for a period of 6 to 7 weeks (total dose 6200 cGy to 7400 cGy). Potential complications include impotence, incontinence, cystitis, urethral strictures, prostatitis, diarrhea, edema of the lower extremities and bone marrow suppression. Patients also may become physically tired, and they should be instructed to get as much rest as possible during their course of treatment. It is not uncommon for erythema to develop and for the skin to become red or dry in the area of treatment. Affected skin should be exposed to the air as much as possible and patients should be instructed to avoid wearing tight clothing. Patients also must be instructed not to use creams or lotions on affected skin without their doctor’s approval (1996).   Support Mechanisms Available to these Patients within the Radiotherapy Department               Acute radiation sickness usually follows therapeutic irradiation. It is characterized by nausea, vomiting, diarrhea, anorexia, headache, malaise, and tachycardia of varying severity. The discomfort subsides within a few hours or days. Nutrition management of the client with cancer focuses on maximizing intake of nutrients and fluids ( 2004).             Psychological interventions are also available for prostate cancer patients who underwent radiotherapy. These are usually handled by nurses. Response to this intervention has been very positive from both nurses and patients, nurses feel that they are better equipped to help patients emotionally and patients feel better able to cope with what can be a very traumatic time ( 2005).       Credit:ivythesis.typepad.com

PROSTATE CANCER

PROSTATE CANCER Prostate Cancer Incidence, Diagnosis and Staging Cancer of the prostate gland is a common cause of de...

WHAT IS CO-MORBIDITY?

WHAT IS CO-MORBIDITY?   It is the presence of coexisting or additional diseases with reference to an initial diagnosis. It describes the effect of all other diseases an individual patient might have other than the primary disease of interest. The term “co-morbidity” has been used to describe the overlap of illnesses which tend to occur together.  “Co” means together or jointly. “Morbidity” refers to disease.  Co-morbidity simply means diseases which occur simultaneously.  According to (1986), “co-morbidity by linking all the various syndromes to a common causal factor – toxicity within the body.  As the body seeks to eliminate toxins, the internal pollution affects various organs producing a variety of symptoms diagnosed as separate illnesses.” Harris, M.,  (2001). Writing labs and the Hollywood connection. However, co-morbidity was also defined as two or more medical conditions that occur at the same time. From a psychiatric point of view, co-morbidity are also called dual diagnosis since the existence of a psychiatric order such as depression, anxiety and  psychotic condition with a chemical dependence disorder, such as chronic alcohol, cannabis, cocaine dependence, etc. goes together. It implies that the illnesses a person may get or feeling are equal though it is not. For instance, one illness can be easily treated while the other one is more severe or even fatal, and one may be mutable. . It also defines each of these disorders as caused by another medical condition which would include the chemical dependencies. This sets the stage for the whole issue of co-morbidity. Unfortunately, alcohol misuse has become a growing problem to all the people who are having co-morbidities. According to the surveys it suggests that the misuse of alcohol or other drugs is a common cause of physical and mental health problems of the people. The alcohol abuse has clear and profound effects on the health and well-being of the people in all aspects of life. Many different organ systems can be damaged by misuse. It has negative effects on self-esteem, coping skills, and interpersonal relationships, which can add to other losses that are common in the stages of life. Also, alcohol and substance when misuse can cause serious illness, worsen other medical conditions, interfere with needed medications, and greatly decrease overall quality of life. Like alcohol, the substance particularly drugs when misuse can bring havoc to one’s life. The problem of misusing the drug substances is seen in people at different ages, genders, races and nationality.  The inappropriate use of prescription or over-the-counter medications are examples of misused drugs It include sedatives, hypnotics, pain relievers, diet aids, decongestants, and a wide variety of over-the-counter medications. The medical problems from misuse also include mental changes, kidney disease, liver disease, injuries from falls and worst, leads to co-morbidity. (2006). Substance Abuse. Since the co-morbidity has gained its popularity in mental health professionals there is a gradual decline of their  role in the field of chemical dependency that connects to non-psychiatric interventions for treating the chemically dependent person. Co-morbidity must be scientifically approached with an open awareness that the co-morbid condition can be induced by drugs, alcohol and genes. Once a mental health professional found out that the patient is having a dual diagnosis for instance, that particular patient will be treated first with what is the more serious illness he had. Consequently, co-morbidity conditions are treated simultaneously but not equally. People who are experiencing the psychiatric disorder were treated and follow-up care is recommended, but nothing other than detoxification for the alcohol abuse. There was no consideration given to the possibility of alcohol dependence or the need for abstinence. There was also no consideration that alcohol might be inducing or worsening the mental disorder. The research indicates that between the half of 100 percent of bipolar patients are addicted to alcohol or drugs. And the other half percentage of patients with anxiety disorders who have co-morbid alcohol syndromes, and 50-90 percent of schizophrenics have a substance-related disorder. Co-morbidity indicates that there is no induction of one illness by another. The studies show that the use of alcohol or drugs in this case may significantly worsen the mental disorder. It does not require an extended period of abstinence or the development of a recovery program to determine if actual co-morbidity exists over time. According to (1998), “the solution to the issue of co-morbidity involves taking both forks in the road and treating each condition simultaneously, but with the awareness that the psychiatric condition may disappear if it has been induced by drugs or alcohol. If the psychiatric condition and chemical dependency are truly co-morbid and equal, they will be treated simultaneously, with abstinence from drugs and alcohol, a recovery program and appropriate mental health interventions”. Thus, it is very essential to consider co-morbidity illnesses determine that one illness is not induced or taken by the other. This can be recognized by talking or interacting to the person involved with collateral evidence, such as family members, to know whether the psychiatric illness occurred after the use of drugs or alcohol. Furthermore, if drugs or alcohol have induced the psychiatric disorder, then the course of psychiatric treatment should be directed toward an appropriate recovery program and abstinence before assuming the primacy of the mental disorder. It is also very important to monitor the use of alcohol and drugs in the person who are being treated for psychiatric conditions, knowing that substance abuse may induce relapses or worsen the mental disorder, especially those of schizophrenia or bipolar disorder. Otherwise, if the alcohol use is not controlled, the person involved will relapse frequently, have increasing symptoms and require expensive hospitalization. These primary psychiatric patients can be directed to abstinence-based recovery programs that are able to accept symptoms of mental disorders. Co-morbidity. Alternate Methods Of Treatment.   Credit:ivythesis.typepad.com

WHAT IS CO-MORBIDITY?

WHAT IS CO-MORBIDITY? It is the presence of coexisting or additional diseases with reference to an initial diagnosis. It describes ...

CUSHING’S SYNDROME

CUSHING’S SYNDROME   1. Description of the disorder The clinical picture produced by prolonged increases in plasma glucocorticoids was described Harvey Cushing, and is called Cushing’s syndrome. It may be (adrenocorticotropic hormone) ACTH-independent or ACTH-dependent. The causes of ACTH-independent Cushing’s syndrome include glucocorticoid-secreting adrenal tumors and prolonged administration of exogenous glucocorticoids for diseases such as rheumatoid arthritis. The causes of ACTH-dependent Cushing’s syndrome include ACTH-secreting tumors of the anterior pituitary gland and tumors of other organs, usually the lungs, that secrete ACTH (ectopic ACTH syndrome) or CRH (2001). Suprarenal cortical hyperplasia is the most common cause of Cushing’s syndrome, the clinical manifestations of which include moon-shaped face, truncal obesity, abnormal hairiness (hirsutism), and hypertension; if the syndrome occurs later in life, it may result from an adenoma or carcinoma of the cortex (Snell). The increased adrenal hormone production of Cushing’s syndrome is responsible for the round or moon face with red cheeks that is characteristic of Cushing’s syndrome (2003).   2. Anatomy             Patients with Cushing’s syndrome are protein-depleted as a result of excess protein catabolism. The skin and subcutaneous tissues are therefore thin, and the muscles are poorly developed. Wounds heal poorly, and minor injuries cause bruises and eccymoses. The hair is thin and scraggly. Many patients with the disease have some increase in facial hair and acne, but this is caused by the increased secretion of adrenal androgens and often accompanies the increase in glucocorticoid secretion (2001). Excessive hair growth may be present in the mustache and sideburn areas and on the chin (2003).             Body fat is redistributed in a characteristic way. The extremities are thin, but fat collects in the abdominal wall, face, and upper back, where it produces a “buffalo hump.” As the thin skin of the abdomen is stretched by the increased subcutaneous fat depots, the subdermal tissues rupture to form prominent reddish-purple striae. These scars are seen normally whenever there is a rapid stretching of skin (e.g. around the breasts of girls at puberty or in the abdominal wall during pregnancy), but in normal individuals, the striae are usually inconspicuous and lack the intense purplish color (2001).             Cushing’s syndrome is characterized biochemically by excess production of glucocorticoids and clinically by central obesity, moon face, buffalo hump, diabetes mellitus, osteoporosis, hypertension, plethora, hirsutism, amenorrhea, acne, weakness and emotional liability ( 1998).   3. Target group             Cushing’s syndrome is relatively rare and most commonly affects adults aged 20 to 50. An estimated 10 to 15 of every million people are affected each year.   4. Diagnostic testing             The full blown symptom complex of Cushing’s syndrome constitutes a not easily missed clinical syndrome. The differential diagnosis of the major categories of Cushing’s syndrome are dexamethasone suppression tests and plasma ACTH levels.             Tests to confirm high cortisol levels include cortisol and urine tests, dexamethasone suppression test and tests fro serial serum cortisol levels. Tests to determine the cause includes ACTH tests, cranial MRI or cranial CT scan which may show anterior pituitary tumor, and abdominal CT which may show adrenal mass. General findings for Cushing’s syndrome include elevated glucose test, low potassium test and elevated white blood cell count.   5. Health promotion strategies             Treatment of Cushing’s syndrome depends on the cause of excess cortisol. If the cause is long-term use of a medication being used to treat another disorder, the physician may reduce the dosage until symptoms are under control. Surgery or radiotherapy may be used to treat pituitary adenomas. Surgery, radiotherapy, chemotherapy, immunotherapy, or a combination of these may be used to treat ectopic ACTH syndrome. The aim of surgical treatment is to cure hypercortisolism by removing the tumor while minimizing the chance of endocrine deficiency or long-term dependence on medications. Tumor removal may lead to full recovery, but there is a chance of recurrence. Survival for people with ectopic tumors depends upon the overall outcome associated with the particular tumor type. Untreated, Cushing’s syndrome can lead to death.   6. Follow up             If ACTH secretion cannot be easily decreased by the usual treatments for Cushing’s syndrome, the only satisfactory treatment is usually bilateral partial (or even total) adrenalectomy. The patient may need steroid replacement therapy after surgery because they may no longer be producing sufficient amounts of cortisol in the adrenal glands. Administration of adrenal steroids will make up for any insufficiency that develops.   7. Long term care The various forms of Cushing’s syndrome are eminently treatable however the condition usually requires long-term care and follow up. Some patients may require life long steroid replacement therapy. As previously stated, Cushing’s syndrome is potentially fatal if left untreated.           Credit:ivythesis.typepad.com

CUSHING’S SYNDROME

CUSHING’S SYNDROME 1. Description of the disorder The clinical picture produced by prolonged increases in plasma glucocorticoids wa...

Encephalitis

Encephalitis is an acute inflammatory disease of the brain due to direct viral invasion or to hypersensitivity initiated by a virus or other foreign protein. If the same disorder affects the spinal cord structures as well as the brain, it is now called an encephalomyelitis.             Virus infection may cause encephalitis as a primary manifestation or as a secondary complication. Viruses causing primary encephalitis may be epidemic (arbo-, polio-, echo-, and coxsackie viruses) or sporadic (herpes simplex, herpes zoster).             Most cases of encephalitis occur as a complication of viral infection and are considered to have an immunologic mechanism. Very rarely, encephalitis or other encephalopathies occur as a late consequence of viral infections.             Viral central nervous system (CNS) infections must be differentiated from nonviral and noninfectious causes, but the major diagnostic problem is differentiation from acute or partially treated bacterial meningitis. Diagnosis is usually based on the cerebrospinal fluid (CSF) characteristics, including normal glucose and failure to grow bacteria on culture. Even under ideal circumstances, viruses causing aseptic meningitis and encephalitis are identified in fewer than half the cases.             Viruses are occasionally isolated directly from the CSF or from other tissues. A precise diagnosis, however, usually requires the use of paired serums documenting the rise in antibodies. Since many forms of encephalitis and aseptic meningitis have important public health implications, serum should be drawn and preserved whenever the diagnosis of encephalitis or aseptic meningitis of uncertain etiology is first suspected.             Physical examination is not very helpful, as the findings do not usually point to a specific etiology. Focality, in particular, is almost always-although not uniformly–present in herpes simplex infections, but also can suggest other diseases (2006).             Although herpes simplex encephalitis is clinically similar to other viral encephalitides, repeated seizures occurring early in the course, and localizing signs indicating temporal or frontal lobe involvement, strongly suggest herpes simplex as the cause. The virus is rarely present in the CSF, and serologic tests are not sufficient to implicate herpes simplex virus since antibody levels normally fluctuate even in healthy persons. Diagnosis is certain only upon demonstration of the virus (by recovery of the virus or immunologic techniques) in cerebral tissue obtained by brain biopsy or at a postmortem examination.             The staged approach begins with first-line testing for the most likely causes. It is recommended that cerebrospinal fluid (CSF) polymerase chain reaction (PCR) be used for testing for herpes simplex virus and enterovirus (2006).             In first-line testing, it should also include evaluation of symptomatic body sites and, if suggested clinically or by epidemiologic history, tests for exposure-related pathogens requiring specific treatments, such as tuberculosis (2006).             If the first line testing does not produce a diagnosis, a second line of testing should be engaged. This would include Epstein-Barr serology; Mycoplasma pneumoniae CSF and throat PCR; testing for animal-related pathogens for which there have been relevant exposures; and tests for vectorborne pathogens, such as West Nile virus and other arborviruses, and for Lyme disease, if the epidemiology suggests possible exposures ( 2006).             As a third line, recommended tests for miscellaneous pathogens if they fit the clinical context, include tests such as parvovirus PCR and serology; human immunodeficiency virus PCR and serology; and tests for other specific exposure-related pathogens (2006).             In one study, researchers discovered that T-cells produce a protein, interferon-[gamma], which can clear the virus in neurons located in the spinal cord and brain stem, but not in neurons located in the cerebral cortex ( 2002). During the experiments, researchers observed that, using interferon-[gamma], CD4 and CD8 T-cells both successfully cleared the virus in the neurons from the spinal cord and brain stem. The neurons in the brain cortex, however, did not react to the interferon-[gamma] in the same manner. This result indicated a site-specific response among neurons to the clearance mechanism. In addition, the researchers observed that another protein produced by the T-cells, tumor necrosis factor [alpha], was unable to clear the virus from the central nervous system.   Credit:ivythesis.typepad.com

Encephalitis

Encephalitis is an acute inflammatory disease of the brain due to direct viral invasion or to hypersensitivity initiated by a...

ATAXIA TELANGIECTASIA

ATAXIA TELANGIECTASIA               Ataxia Telangiectasia (AT) is an autosomal recessive hereditary progressive neurodegenerative and multisystem disease characterized by cerebellar ataxia, telangiectasias, recurrent sinopulmonary infections, and variable immunologic defects. Its diagnosis is obvious when ataxia and telangiectasia are both present. However, the diagnosis can be made upon the onset of ataxia and before the appearance of telangiectasia if confirmed by laboratory tests. Early diagnosis is important for genetic counseling, appropriate care, and avoidance of unnecessary tests (1998).               Serum IgA is low to absent in 60 to 80% of cases; less common B cell defects include low to absent secretory IgA, increased catabolism of serum IgA, development of anti-IgA, and deficiency of serum IgE. Evidence of impaired T cell function includes periodic lymphopenia, a decreased response to delayed hypersensitivity tests and to in vitro tests of lymphocyte function, and thymus abnormalities (small gland; decreased lymphocytes; absence of Hassall’s corpuscles).               Both neurologic symptoms and evidence of immunodeficiency are variable in onset. Ataxia usually develops at about the time when patients begin to walk but may be delayed until the age of four years. Its progression leads to severe disability. Speech becomes slurred, choreoathetoid movements and opthalmoplegia occur, and muscle weakness usually progresses to muscle atrophy.               Telangiectasias develop between 1 and 6 years of age, most prominently on the bulbar conjunctiva, ears, antecubital and popliteal fossas, and sides of the nose. The recurrent sinopulmonary infections, which result from the immunologic deficits, lead to recurrent pneumonia, bronchiectasis, and chronic obstructive and restrictive lung disease.               Endocrine abnormalities may occur, including gonadal dysgenesis, testicular atrophy, and an unusual form of diabetes mellitus characterized by marked hyperglycemia, resistance to ketosis, absence of glycosuria, and a marked plasma insulin response to glucose or tulbutamide.               The incidence of cancer is increased, most often as lymphosarcoma but also including Hodgkin’s disease, leukemia, gastric adenocarcinoma, cerebellar medulloblastoma, reticulum cell carcinoma, and frontal lobe glioma.               Prognosis is usually poor, with death occurring from chronic sinopulmonary infections or malignancy. However, the progressively and severely handicapped patients may survive into their 30s.               Proper diagnosis of the hereditary disorder AT can be done when only the ataxia or staggering balance problems have appeared but not the telangiecatasia with its characteristic dilation of capillaries on the ears, faces, and eyes. The name of the disorder itself is an impediment to early diagnosis, as it includes both symptoms. A serum alpha-fetoprotein test done on all children who have a lasting ataxia would identify the AT earlier and allow treatment and counseling (1998).               Although it is difficult to reconstruct all the factors that lead physicians to a correct diagnosis of AT, we hypothesize that physicians rely on telangiectasia to make this diagnosis and do not consider AT until telngiectasia appear. This may be attributable to the fact that AT is a rare cause of ataxia and/or the physician’s unfamiliarity with laboratory methods that may support a diagnosis at an earlier stage of the disease. Furthermore, affected children may not seem to deteriorate in function until the early school years so that the diagnosis of a static condition seems reasonable for a time. Our experience with AT suggests that the name, although a concise and memorable label for the disorder, is also a barrier to early diagnosis ( 1998).               Laboratory tests that may help support a diagnosis of AT include measurement of serum AFP levels and examination of the karyotype. AFP is a human fetal serum protein found at levels less than 10 ng/mL in children more than the age of 1 year. Rising levels of AFP in young children are distinctly unusual, and characteristic of patients with AT or certain rare tumors. Increased frequency of spontaneous- and x-irradiation-induced chromosomal breaks are also associated with the diagnosis of AT. Recent identification of the gene responsible for AT (ATM) may improve diagnosis and reveal a wider spectrum of the disease. However, the large size of the ATM gene and the finding that most pathogenic mutations are unique make genetic evaluation of the individual patient highly labor intensive and genetic diagnosis more specific than sensitive (1998).               Although the AT is diagnosed based on clinical presentation as is presented in the first few paragraphs, it is sometimes necessary to perform a cytological test to confirm diagnosis. This is done by demonstrating that cells from patients are sensitive to irradiation (IR). This procedure is done by irradiating blood lymphocytes, or skin fibroblast cells from AT patients followed by monitoring frequencies of CAs in metaphase cells relative to frequencies of CAs found in cells from normal, control individuals. In a typical analysis four cells sampled are generated: untreated AT sample, irradiated AT sample, untreated normal sample, and irradiated normal sample.               As the analysis is performed in a way that the person analyzing the samples is not aware of which sample is which, there is no chance for the experiment to be manually manipulated by the researchers in order to come up with the desired results.               The irradiated normal sample showed a total of 12 chromosomal aberrations. The irradiated AT sample on the other hand had a total of 35 chromosomal aberrations. The untreated AT sample had a total of 6 chromosomal aberrations.               The frequency of chromosomal aberrations induced by radiation in each of the samples was found to be similar in the cells irradiated. A similar frequency was recorded also in the cells of genetically or AT defective individuals. However, the incidence of aberrations in specific chromosomes of normal and genetically defective or AT individuals differed and the frequency was found to be higher in the latter group. From the data it is evident that the response of chromosomes of AT patients was significantly different compared to those of healthy individuals.               The radiosensitivity of individual chromosomes and the location of the radiation-induced chromosomal break points are found to be genetically controlled. There exists an intra and interchromosomal variation in the production of radiation-induced chromosomal aberrations.   A delay in the diagnosis of AT may compromise care of the patient and other family members. Early diagnosis of AT alerts the physician to possible immunodeficiency and the need to limit exposure to ultraviolet light and diagnostic radiographs. Early diagnosis also allows the opportunity for genetic counseling because parents are at risk for having other children with AT. Timely diagnosis identifies heterozygous parents who may have an increased risk for cancer or complications from cancer therapy.   Finally early diagnosis can avoid further costly and unnecessary tests. Many of our patients have had one, if not multiple, neuroimaging studies. In contrast, the cost of determining serum AFP levels is low. On a macroeconomic level, routine determination of AFP for all pediatric patients with chronic ataxia may be cost-effective. AFP measurements are certainly cost-effective in the evaluation of young children with progressive ataxia. In summary, the diagnosis of AT is often delayed, but can be made earlier with readily available and inexpensive laboratory studies. The delay is costly for the patient, family, and society ( 1998).       Credit:ivythesis.typepad.com

ATAXIA TELANGIECTASIA

ATAXIA TELANGIECTASIA Ataxia Telangiectasia (AT) is an autosomal recessive hereditary progressive neurodegenerative and ...

Osteoarthritis is a chronic, degenerative disease associated with joint pain and loss of joint function. Evaluate the evidence to discuss in physiological terms why osteoarthritis results in chronic pain.

Osteoarthritis is a chronic, degenerative disease associated with joint pain and loss of joint function. Evaluate the evidence to discuss in physiological terms why osteoarthritis results in chronic pain.   Introduction             The most common form of arthritis is osteoarthritis (2004), also called degenerative joint disease. The latter name is especially appropriate because this form of arthritis which appears with advancing years, is not primarily an inflammatory process as are most of the others but is due to degenerative changes in the cartilaginous portions of joints and in bones. It is characterized by degenerative loss of articular cartilage that lines and lubricates the joints, subchondral bony sclerosis, and cartilage and bone proliferation at the joint margins with subsequent osteophyte formation. The ends of the bones within the joint are thus left unprotected, leading to pain and stiffness. It is also called “wear-and-tear” arthritis. Over the years, there is a softening, fraying, and eventual breakdown of the cartilage. As the disease progresses, the exposed bone thickens and extra bone tissue, called bone spurs, grows around the margins of the eroded cartilage. The bone spurs protrude into the joint cavity. Patients complain of stiffness on arising that lessens with activity, and the affected joints may make a crunching noise (crepitus) when moved. The joints most commonly affected are those of the fingers, the cervical and lumbar joints of the spine, and the large, weight-bearing joints of the lower limbs (2004). Clearly, an important factor is wear and tear. Hence it is more apt to appear in weight-bearing joints of persons who are overweight, or in joints which have been damaged by some other form of arthritis, injuries or congenital defects.             The course of osteoarthritis is usually slow, but it is rarely crippling. In most cases, its symptoms are controllable with a mild analgesic such as aspirin, moderate activity to maintain joint mobility, and rest when the joint becomes very painful ( 2004). The pattern of spread is additive; however, only one joint may be involved. It is slowly progressive, with temporary exacerbations after periods of overuse ( 2003). Few data are available on the incidence of osteoarthritis because of the problems of defining it and how to determine its onset. It afflicts millions around the world. However, only a small fraction of this number is significantly incapacitated. The prevalence of osteoarthritis increases indefinitely with age, because the condition is not reversible. Men are affected more often than women among those 45 years and below, whereas women are affected more frequently among those 55 years and above (2003).   Etiology and Incidence             The cause is unknown, but genetic, metabolic, endocrine, biochemical, and hydrolytic enzyme factors have been suggested. Abnormal biochemical stresses may lead to chondrocyte damage and proteolytic enzyme release resulting in articular cartilage degeneration. Osteoarthritis may also be secondary to chronic trauma or underlying joint disease.             Aging is the single most important factor in the development of osteoarthritis. Virtually all persons over the age of 50 have at least traces of this condition. However, it should be pointed out that some aged individuals have little evidence of it, whereas other, relatively young, persons may develop widely disseminated incapacitating arthritis (1998).             Osteoarthritis is an insidious disease that is usually first noticed as a slight stiffness or decreased mobility in the affected joints. It is generally believed that faulty posture, obesity and occupational stress all predispose to the development of the condition. As the patient ages, the pain, stiffness and limited motion become more marked. There are no constitutional signs of an inflammatory disease, and the joints rarely have local evidence of inflammation. Usually, the disorder is slowly progressive over the remaining years of life ( 1998). A small number of the cases of osteoarthritis are due to mutations in the COL1A genes. In various types of arthritis, proteoglycans may act as autoantigens, thus contributing to the pathologic features of these conditions. The amount of chondroitin sulfate in cartilage diminishes with age, whereas the amounts of keratin sulfate and hyaluronic acid increase. These changes may contribute to the development of osteoarthritis (2000).   Pathology             Osteoarthritis is a non-inflammatory disease of joints characterized by deterioration and erosion of articular cartilage and by the formation of new bone at the articular margins sometimes producing so-called spurs (1998).  Osteoarthritis may occur as a monoarticular or polyarticular involvement. The large joints of the body and the spine are principally affected. The principal anatomic alterations are degeneration of the cartilage rather than inflammation of the synovia.             With the destruction of the articular cartilage, the underlying bone is exposed. The subarticular bone becomes thickened because of either compression or new bone formation. The marrow spaces in this region are often filled with fibrous tissue and small islands of cartilage that are either driven in by traumatic injury or are formed from the endosteum or connective tissue in the marrow spaces. At the same time, small islands of cartilage, which later become ossified, project above the surface of the articular cartilage, usually about its margins, to produce the characteristic bony spurs of osteoarthritis. When large spurs project from opposing bones, they may come into contact with each other to cause pain and limitation of motion (1998). Grossly, the cartilage becomes yellow-white and soft. Fibrillation, pitting, and ulcers are found in superficial cartilage layers. Marginal osteophytes form. Histologically, fissuring and fibrillation are prominent. Degenerating chondrocytes and reactive clonal chondrocyte proliferation are present. Subchondral bone is thickened; cyst formation occurs. Synovitis is mild to moderate.   Symptoms and Signs             Onset is usually gradual and localized to one or a few joints. The main symptoms are pain aggravated by motion or the pressure of weight, stiffness after inactivity, and limitation of motion (1998). Pain is greatest after exercise. Stiffness or fibrosis commonly follows inactivity but is usually of short duration. Joint motion is limited in severe cases. Tenderness and crepitus or grating are present. Joint enlargement is present due to proliferative chondrocyte reactions in cartilage and bone. Synovial effusion may occur. Deformity and subluxation are late findings. Constitutional symptoms and extra-articular manifestations are absent.             The specific clinical picture varies with the joints involved. Enlargement of the terminal interphalangeal joints, called Heberden’s nodes (Koestler & Myers, 2002), is common; painful gelatinous cysts may also be present. Women are affected by this form of disease ten times as often as men. Similar deformities may develop at the proximal interphalangeal joints (Bouchard’s nodes). Disease of the first carpometacarpal joint causes pain and limitation of use of the thumb. Knee involvement produces pain, swelling and instability. Osteoarthritis of the hip causes local pain and a limp (Snell, 2000. Spinal osteoarthritis is common; severe degenerative changes may occur without symptoms. Osteoarthritic changes are most common in the midcervical and lower lumbar areas of maximal spinal motion. Compression of contiguous neurologic structures by large osteophytes or a degenerated disc may cause severe radicular pain. Vascular insufficiency syndromes may follow compromise of cervical vascular structures.   Physiology of Pain             Many, if not most, ailments of the body cause pain. The sense organs for pain are the naked nerve endings found in almost every tissue of the body. Pain has been classified into two major types: fast pain and slow pain. Fast pain is felt within about 0.1 second after a pain stimulus is applied, whereas slow pain begins only after 1 second or more and then increases slowly over many seconds and sometimes even minutes (2000). Fast pain is also described in many alternative names, such as sharp pain, pricking pain, electric pain and acute pain. Acute pain is generally the result of a specific injury and can be clearly explained in terms of where we feel it in the body. This type of pain is felt when a needle is stuck into the skin, when the skin is cut with a knife, or when the skin is acutely burned. It is also felt when the pain is subjected to electric shock. Fast, sharp pain is not felt in most deeper tissues of the body.             Slow pain also goes by multiple additional names, such as slow burning pain, aching pain, throbbing pain, nauseous pain, and chronic pain. This type of pain is usually associated with tissue destruction. It can lead to prolonged, unbearable suffering. It can occur both in skin and in almost any deep tissue or organ. Chronic pain is the other type of pain which is so called because it can continue for months or years and even trigger additional health problems such as depression and lead to lifestyle changes in attempts to remedy the situation. It is pain that has not responded to traditional medical interventions, or one for which a medical “cure” is not available (2002).             Osteoarthritis or joint inflammation is a type of slow or chronic pain. Pain of musculoskeletal origin – as the case of osteoarthritis – largely results from overstimulation of nerve endings. The nerve endings may be stimulated by inflammatory substances that are produced by damaged cells and released from the surrounding capillary network. The resulting sensitization results to a lower pain threshold so that even a mild stimulus like pressure and joint motion are interpreted as pain. The pain receptors, also called nociceptors, in the skin and other tissues are all free nerve endings. They are widespread in the superficial layers of the skin as well as in certain internal tissues, such as the joint surfaces. Most other deep tissues are not extensively supplied with pain endings but are sparsely supplied; nevertheless, any widespread tissue damage can still summate to cause the slow-chronic-aching type of pain in most of these areas (2000).             Pain can be elicited by multiple types of stimuli. They are classified as mechanical, thermal, and chemical pain stimuli. Slow pain can be elicited by all three types. Some chemicals that excite the chemical type of pain are bradykinin, serotonin, histamine, potassium ions, acids, acetylcholine, and proteolytic enzymes. In addition, prostaglandins and substance P enhance the sensitivity of pain endings but do not directly excite them. The chemical substances are especially important in stimulating the slow, chronic type of pain that occurs after tissue injury.             In contrast to most other sensory receptors of the body, the pain receptors adapt very little and sometimes not at all. In fact, under some conditions, the excitation of the pain fibers becomes progressively greater, especially so for slow-aching-nauseous pain, as the pain stimulus continues. This increase in sensitivity of pain receptors is called hyperalgesia (2000).             One can readily understand the importance of this failure of pain receptors to adapt, because it allows the pain to keep the person apprised of a tissue-damaging stimulus as long as it persists (2000).             The average person first begins to perceive pain when the skin is heated above 45°C. This is also the temperature at which the tissues begin to be damaged by heat; indeed, the tissues are eventually destroyed if the temperature remains above this level indefinitely. The intensity of pain is also closely correlated with the rate of tissue damage from other causes as well as from heat – bacterial infection, tissue ischemia, tissue contusion, and so forth.             Even though all pain receptors are free nerve endings, these endings use two separate pathways for transmitting pain signals into the central nervous system. The two pathways mainly correspond to the two types of pain, a fast-sharp pain pathway and a slow-chronic pain pathway (2000).             The slow-chronic type of pain is mostly elicited by chemical types of pain stimuli but also at times by persisting mechanical or thermal stimuli (2000). Pain impulses are transmitted to the central nervous system by two fiber systems. The nociceptor system responsible for the pain felt in osteoarthritis consists of unmyelinated (2001) C fibers 0.4-1.2 µm in diameter. This slow-chronic pain is transmitted in the peripheral nerves to the spinal cord by the type C fibers at velocities between 0.5 and 2 m/sec. These roots are found in the lateral division of the dorsal roots and are often called dorsal root C fibers (2001). A separate peripheral pain type A delta fiber also carries the fast-sharp pain stimuli.             Because of this dual system of pain innervation, a sudden painful stimulus often gives a double pain sensation: a fast-sharp pain that is transmitted to the brain by the A fiber pathway followed a second or so later by a slow pain that is transmitted by the C fiber pathway.             The sharp pain apprises the person rapidly of a damaging influence and, therefore, plays an important role in making the person react immediately to remove himself or herself from the stimulus. The slow pain tends to become greater over time. This sensation eventually gives one the intolerable suffering of long-continued pain and makes the person continue to try to relieve the cause of pain.             On entering the spinal cord from the dorsal spinal roots, the pain fibers terminate on neurons in the dorsal horns. Here again, there are two systems for processing the pain signals on their way to the brain (2001).             On entering the spinal cord, the pain signals take two pathways to the brain, through (1) the neospinothalamic tract and (2) the paleospinothalamic tract. The neospinothalamic tract is the pain pathway for fast or acute pain (2000).             The paleospinothalamic pathway is an older system and transmits pain mainly from the peripheral slow-chronic type C pain fibers, although it does transmit some signals from type A fibers as well. In this pathway, the peripheral fibers terminate almost entirely in laminae II and III of the dorsal horns, which together are called substantia gelatinosa (2000).  The synaptic junctions between the peripheral nociceptor fibers and the dorsal horn cells in the spinal cord are the sites of considerable plasticity. For this reason, the dorsal horn has been called a gate, where pain impulses can be “gated” or modified ( 2001).             Most of the signals then pass through one or more additional short fiber neurons within the dorsal horns themselves before entering mainly lamina V, also in the dorsal horn. Here the last neuron in the series gives rise to long axons that mostly join the fibers from the fast pain pathway, passing first through the anterior commissure to the opposite side of the cord, then upward to the brain in the anterolateral pathway.             Research experiments suggest that the type C pain fiber terminals entering the spinal cord secrete both glutamate transmitter and substance P transmitter. The glutamate transmitter acts instantaneously and lasts for only a few milliseconds. Conversely, substance P is released much more slowly, building up in concentration over a period of seconds or even minutes (2000).             The slow-chronic paleospinothalamic pathway terminates widely in the brain stem. Only one tenth to one fourth of the fibers pass all the way to the thalamus. Instead, they terminate principally in one of the three areas: (1) the reticular nuclei of the medulla, pons, and mesencephalon; (2) the tectal area of the mesencephalon deep to the superior and inferior colliculi; or (3) the periaqueductal gray region surrounding the aqueduct of Sylvius (2000).             These lower regions of the brain appear to be important in the appreciation of the suffering types of pain because animals with their brains sectioned above the mesencephalon to block any pain signals reaching the cerebrum still evince undeniable evidence of suffering when any part of the body is traumatized.             From the brain stem pain areas, multiple short-fiber neurons relay pain signals upward into the intralaminar and ventrolateral nuclei of the thalamus and into certain portions of the hypothalamus and other adjacent regions of the basal brain (2000).             Localization of pain transmitted in the paleospinothalamic pathway is poor. For instance, the slow-chronic type of pain can usually be localized only to a major part of the body, such as to one arm or leg but not to a specific point on the arm or leg. This is in keeping with the multisynaptic, diffuse connectivity of this pathway. It explains why patients often have serious difficulty in localizing the source of some chronic types of pain. A simplified diagram of the pain pathway in osteoarthritis is provided below:     Complete removal of the somatic sensory areas of the cerebral cortex does not destroy an animal’s ability to perceive pain. Therefore, it is likely that pain impulses entering the brain stem reticular formation, the thalamus, and other lower centers can cause conscious perception of pain. This does not mean that the cerebral cortex has nothing to do with normal pain appreciation; indeed, electrical stimulation of the cortical somatosensory areas causes a human being to perceive mild pain in about 3 per cant of the pints stimulated. It is believed that the cortex plays an important role in interpreting the quality of pain, even though pain perception might be principally a function of lower centers (2000).             It has been suggested that pain is chemically mediated and that stimuli which provoke it have in common the ability to liberate a chemical agent that stimulates the nerve endings. The chemical agent might be Adenosine Triphosphate (ATP). ATP opens ligand-gated channels on sensory neurons via P2X receptors (2001).   Analysis and discussion             Volumes of printed articles and books already stress the pain that is felt in osteoarthritis. However, there is only limited information regarding the physiologic pathway of the pain in osteoarthritis. Literature regarding the specific events that occur inside the body in the transmission of pain in osteoarthritis is very limited. Most articles or journals offer only a brief overview on the pain felt but do not dig deeper into the pain pathway itself. Most information regarding the pathway of pain is found in physiology books. Many websites offer information on pain. But it deals mostly with the cause of pain, its description and its management. There are though a small number of websites that provide sufficient understanding on the pathway of pain.  provided a very detailed pathway of pain which results from tissue destruction – which is the case for osteoarthritis. Although the discussion in their book is not specific to the pain in osteoarthritis alone, it generally applies to pain that is felt from tissue destruction or that which is felt from any deep tissue or organ.  also provided that specific chemical agents can trigger the pain in osteoarthritis that will set off the pain transmission through the pathway. Although the literature regarding the pain pathway of osteoarthritis is very limited, the books and other sources used for this research offered relevant and useful information in understanding the pain pathway. The information offered in the books is already accepted and held true in the entire medical field.             Summarization and Conclusion The chronic (persistent) pain experienced by individuals with osteoarthritis may be caused by the ongoing tissue damage. Osteoarthritis dries out the protective and lubricating properties of the cartilage which in turn starts to soften and crack.  As a result, abnormal bone hardening can occur in the body’s effort to repair itself, fluid can build up in pockets around the affected bone, and as the cartilage wears away, the bony spurs rub together causing pain. Repetitive activation of nociceptors can sensitize the paleospinothalamic neural pathway and produce the pain felt in osteoarthritis. Credit:ivythesis.typepad.com

Osteoarthritis is a chronic, degenerative disease associated with joint pain and loss of joint function. Evaluate the evidence to discuss in physiological terms why osteoarthritis results in chronic pain.

Osteoarthritis is a chronic, degenerative disease associated with joint pain and loss of joint function. Evaluate the evidence to discuss...