Gene/Protein Disease Symptom Drug Enzyme Compound
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This report examines health care costs in the panel of one HMO physician in relation to enrollee health status. High cost enrollees, 15% of the practice panel, accounted for 64% of total costs. For all 722 patients included in the study, the components of costs were: ambulatory visits, 40% of total costs; impatient care, 31%; pharmacy services, 10%; radiology services, 5%; and laboratory services, 4%. Patients with severe physical disease (8% of all enrollees) accounted for about one-third of total costs, while those with moderate physical disease (27% of all enrollees) accounted for an additional one-third. Patients treated for 12 chronic conditions accounted for almost two-thirds of total costs. These conditions were (in order of the contribution of patients with each condition to total costs): hypertension, cancer, abdominal pain, heart disease, diabetes, back pain, headache, depression, arthritis, chronic obstructive pulmonary disease, fatigue, and anxiety. Enrollees treated for one or more of these 12 conditions (37% of the practice panel) accounted for 61% of the high cost enrollees and 63% of total costs. Controlling health care costs will require cost effective systems of care for these common chronic conditions. At present, HMOs typically rely on individual providers to manage these common chronic conditions on a case by case basis, rather than organizing clinic-and HMO-wide systems of care. HMO research and quality improvement programs aimed at improving cost effectiveness might productively focus on how practice teams, clinics and the delivery system as a whole could improve the management of the common chronic conditions which affect high cost enrollees.
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PMID:High cost HMO enrollees. Analysis of one physician's panel. 1011 59

Coexisting diseases may have unforeseen yet clinically significant effects on patients' well-being. Both generic and disease-specific measures are frequently used to assess health-related quality of life (QOL). The present study assessed the effects of comorbidity on the results of QOL measures through an analysis of longitudinal data from 3 double-masked, randomized, placebo-controlled clinical trials dealing with heartburn, asthma, and ulcer. Patients were assigned to subgroups by comorbidity status: those with no comorbid diseases and those whose principal disease was heartburn, asthma, or ulcer and whose comorbid condition was chronic obstructive pulmonary disease, asthma, or chronic bronchitis; hypertension; migraine, coronary artery disease, or varicose veins; chronic gastrointestinal conditions; arthritis or back pain; diabetes; or depression. Multivariate analysis of covariance was used to test the study hypotheses. The study results suggest that comorbid conditions significantly and extensively affect patients' scores on generic QOL measures and estimation of treatment effect, whereas their influence on disease-specific QOL scores and estimation of treatment effect is considerably smaller. Further, the most important comorbidities in the 3 trial populations were arthritis or back pain and depression, which respectively accounted for 17% and 5% of the patient population. These findings have significant practical implications for the estimation of true treatment effects, control of comorbidity effects, and design of QOL trials.
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PMID:Effects of comorbidity on health-related quality-of-life scores: an analysis of clinical trial data. 1021 40

Skin diseases such as acne are sometimes thought of as unimportant, even trivial, when compared with diseases of other organ systems. To address this point directly, validated generic questionnaires were used to assess morbidity in acne patients and compare it with morbidity in patients with other chronic diseases. For 111 acne patients referred to a dermatologist, quality of life was measured using the Dermatology Life Quality Index, Rosenberg's measure of self-esteem, a version of the General Health Questionnaire (GHQ-28) and the Short Form 36 (SF-36). Clinical severity was measured using the Leeds Acne Grade. Population quality of life data for the SF-36 instrument were available from a random sample of adult local residents (n = 9334) some of whom reported a variety of long-standing disabling diseases. All quality of life instruments showed substantial deficits for acne patients that correlated with each other but not with clinically assessed acne severity. The acne patients (a relatively severely affected group) reported levels of social, psychological and emotional problems that were as great as those reported by patients with chronic disabling asthma, epilepsy, diabetes, back pain or arthritis. Acne is not a trivial disease in comparison with other chronic conditions. This should be recognized in the allocation of health care resources.
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PMID:The quality of life in acne: a comparison with general medical conditions using generic questionnaires. 1023 19

A case of pyogenic infectious spondylitis associated with diabetes was reported. The patient experienced focal back pain 2 weeks after amputation of her left foot due to diabetic gangrene. Magnetic resonance imaging of the lumbar spine revealed decreased T1-weighted signals of Th11 and Th12 vertebral bodies and prevertebral masses, and these lesions were also detected as high signal intensities in T2-weighted magnetic resonance imaging. The images were consistent with a diagnosis of pyogenic infectious spondylitis and the patient responded to treatment with broad-spectrum antibiotics. Percutaneous drainage of the abscesses was also needed. Early magnetic resonance imaging examination was particularly helpful in the accurate diagnosis and treatment of this rare disorder.
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PMID:Pyogenic infectious spondylitis in a patient with diabetes: case report. 1041 61

Pancreatic and biliary carcinomas remain a challenge to clinicians and investigators, as diagnosis is rarely achieved while the tumor is still in a curative stage. Clinical symptoms and signs of these neoplasias are non-specific and heterogeneous. We review the clinical presentation of these tumors, with an emphasis on their pathophysiology and relationship with survival. Abdominal pain is the most common presenting complaint in pancreatic and biliary tract carcinomas, regardless of their size; although severe back pain usually indicates neural compromise, and is associated with a short survival. Jaundice may also be an early sign, in fact, pancreatic tumors that present as painless jaundice have been ascribed, a relatively more favorable prognosis. Weight loss is a common finding in most patients, being usually associated with malabsorption. These neoplasias may also present as diabetes, as an acute pancreatitis episode, with venous thrombosis or malignant thrombophlebitis, as a gastrointestinal hemorrhage, with mental disturbances, or skin manifestations.
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PMID:Vagaries of clinical presentation of pancreatic and biliary tract cancer. 1043 92

The diagnosis of pancreatic cancer usually depends upon symptoms; consequently it is late when there is no chance for cure. At this point, pain, anorexia, early satiety, sleep problems and weight loss are present. Back pain also may be prominent, which predicts unresectability and shortened survival after resection. However, earlier recognition of symptoms of pancreatic cancer might improve early detection of the cancer. For example, 25% of patients have symptoms compatible with upper abdominal disease up to 6 months prior to diagnosis and 15% of patients may seek medical attention more than 6 months prior to diagnosis. These symptoms erroneously may be attributed to problems such as irritable syndrome. Symptoms, however, may be less common. For example a quarter of patients with pancreatic cancer may have no pain at diagnosis, and half, particularly those with pancreatic head tumors, may have little pain compared with patients with body-tail tumors. However, if the tumor is suspected because of predisposing conditions, earlier diagnosis may be possible. These conditions include diseases such as chronic pancreatitis, intraductal papillary mucinous tumor (IPMT), and recent onset of diabetes mellitus, particularly if the diabetes occurs during or beyond the sixth decade. In addition inherited syndromes also are associated with an increased risk of pancreatic cancer including familial pancreatic cancer, hereditary pancreatitis, familial adenomatous polyposis syndrome (FAP) and familial atypical multiple mole melanoma (FAMMM) syndrome (hereditary dysplastic nevus syndrome). Of these conditions, recent onset of diabetes may be the best clue and should be included in a clinical profile of patients prior to the onset of symptoms to identify a high-risk group to apply screening strategies for detection of early disease. Contrary to a clinical aphorism that pancreatic cancer patients are elderly, lean and recently may have developed diabetes, we found that patients who develop pancreatic cancer are overweight prior to onset of symptoms compared to controls (body mass index, 28 vs 25). Forty percent had the diagnosis of diabetes made at the time of diagnosis of pancreatic cancer and more patients with a resectable tumor had diabetes (58%) compared to patients with locally unresectable or metastatic disease (37%). Perhaps, screening overweight persons who have new-onset diabetes may lead to a diagnosis of asymptomatic, early, resectable pancreatic cancer.
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PMID:Pancreatic cancer: clinical presentation, pitfalls and early clues. 1043 7

A 44-year-old woman who weighed 130 kg (height 158 cm, BMI 52) with a complicated psychiatric history was referred for obesity surgery because of severe sleep apnea, obesity hypoventilation syndrome with frequent pneumonias, arterial hypertension, diabetes mellitus, polyarthralgia and back pain, venous insufficiency, dysmenorrhea, severe heartburn, and incisional hernia. From childhood until 1983, she had undergone 106 operations, mainly for septic/pyemic and intra-abdominal abscesses, 86 of them under general anesthesia. In the 4 years before undergoing bariatric surgery, she had gained 40 kg, nonoperative attempts at weight reduction had failed. Some months before obesity surgery she could fall asleep while standing, and she noticed an entire loss of capacity for work. Respiratory disturbance index measured during sleep by Mesam-4 device was 68 events per hour. Preoperative controlled positive airway pressure (C-PAP) therapy was used. Vital indications for weight reduction were established. Bariatric surgical steps included six operations: (1) vertical banded gastroplasty (VBG); (2) relaparotomy with suspicion of peritonitis, no complications found; (3) hernioplasty simultaneously with panniculectomy; (4) revision and removal of additional flap because of marginal skin necrosis; (5) bilateral thigh dermatolipectomy simultaneously with right-side saphenectomy; and (6) removal of intramammary abscess. Twenty-four months after VBG, she had lost 39 kg (56.5 % EWL) and was doing rather well. Obesity-related diseases except back pain were relieved.
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PMID:Successful bariatric surgery in a patient who underwent more than 100 various operations. 1048 18

We describe ten cases of aortitis due to Salmonella that were treated at the University of Toronto-affiliated Hospitals between 1978 and 1997. Predisposing conditions included hypertension, diabetes mellitus, and myelodysplastic syndrome. Main presenting symptoms were fever and abdominal and back pain. The most frequent site involved was the abdominal aorta, followed by the thoracic aorta. All but one patient were treated with intravenous bactericidal antibiotics; seven also underwent surgery, four with axillobifemoral grafts and three with in situ grafts. Four of seven patients died within 1 month of the surgical procedure (three patients with in situ grafts and one patient with axillobifemoral graft). We also reviewed the pathogenesis, clinical and laboratory characteristics, and treatment of 140 cases of aortitis due to Salmonella reported in the literature since 1948. The use of bactericidal antibiotics, together with early surgical intervention and long-term suppressive antibiotic therapy, has led to improved survival.
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PMID:Aortitis due to Salmonella: report of 10 cases and comprehensive review of the literature. 1058 4

We report a patient with a dissecting aortic aneurysm associated with polymyalgia rheumatica (PMR). The patient is a 55-year-old Japanese man without a history of hypertension, diabetes mellitus and syphilis. He was admitted to an emergency hospital because of severe back pain, and was diagnosed as having a dissecting aneurysm of the descending aorta. After the admission, he began to notice severe muscle pain in his bilateral shoulder. Although his back pain gradually improved, his muscle pain progressively worsened, and his lower extremities were also involved. Then, he was introduced to our hospital. On neurological examination, he was alert and oriented. His cranial nerves were all intact. There was no muscle weakness nor sensory disturbance. Laboratory studies revealed that his erhythrocyte sedimentation rate was extremely high without elevation of the serum level of creatine phoshpokinase, rheumatoid factors and c-reactive protein. He was diagnosed as having PMR, and oral administration of prednisolone++ was started. Within several days, his muscle pain dramatically disappeared. As is known, there is a close relationship between PMR and temporal arteritis of giant cell arteritis. In general, PMR is a benign disease and responds well to steroid therapy, and prevalence of the giant cell arteritis is low in Japanese people. However, it should be kept in mind that the dissecting aneurysm is a relevant, severe complication of PMR because arteritis can be latently present in PMR.
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PMID:[The dissecting aortic aneurysm associated with polymyalgia rheumatica: a case report]. 1065 1

Angiotensin II receptor blockers (ARBs) represent a new class of effective and well tolerated orally active antihypertensive agents. Recent clinical trials have shown the added benefits of ARBs in hypertensive patients (reduction in left ventricular hypertrophy, improvement in diastolic function, decrease in ventricular arrhythmias, reduction in microalbuminuria, and improvement in renal function), and cardioprotective effect in patients with heart failure. Several large long-term studies are in progress to assess the beneficial effects of ARBs on cardiac hypertrophy, renal function, and cardiovascular and cerebrovascular morbidity and mortality in hypertensive patients with or without diabetes mellitus, and the value of these drugs in patients with heart disease and diabetic nephropathy. The ARBs specifically block the interaction of angiotensin II at the AT1 receptor, thereby relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume, and decreasing cellular hypertrophy. These agents exert their blood pressure-lowering effect mainly by reducing peripheral vascular resistance usually without a rise in heart rate. Most of the commercially available ARBs control blood pressure for 24 h after once daily dosing. Sustained efficacy of blood pressure control, without any evidence of tachyphylaxis, has been demonstrated after long-term administration (3 years) of some of the ARBs. The efficacy of ARBs is similar to that of thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors or calcium channel blockers in patients with similar degree of hypertension. Higher daily doses, dietary salt restriction, and concomitant diuretic or ACE inhibitor administration amplify the antihypertensive effect of ARBs. The ARBs have a low incidence of adverse effects (headache, upper respiratory infection, back pain, muscle cramps, fatigue and dizziness), even in the elderly patients. After the approval of losartan, five other ARBs (candesartan cilexetil, eprosartan, irbesartan, telmisartan, and valsartan) and three combinations with hydrochlorothiazide (irbesartan, losartan and valsartan) have been approved as antihypertensive agents, and some 28 compounds are in various stages of development. The ARBs are non-peptide compounds with varied structures; some (candesartan, losartan, irbesartan, and valsartan) have a common tetrazolo-biphenyl structure. Except for irbesartan, all active ARBs have a carboxylic acid group. Candesartan cilexetil is a prodrug, while losartan has a metabolite (EXP3174) which is more active than the parent drug. No other metabolites of ARBs contribute significantly to the antihypertensive effect. The variation in the molecular structure of the ARBs results in differences in the binding affinity to the receptor and pharmacokinetic profiles. The differences observed in lipid solubility, absorption/distribution, plasma protein binding, bioavailability, biotransformation, plasma half-life, and systemic elimination influence the time of onset, duration of action, and efficacy of the ARBs. On the basis of the daily mg dose, the antihypertensive potency of the ARBs follows the sequence: candesartan cilexetil > telmisartan approximately = losartan > irbesartan approximately = valsartan > eprosartan. After oral administration, the ARBs are rapidly absorbed (time for peak plasma levels = 0.5-4 h) but they have a wide range of bioavailability (from a low of 13% for eprosartan to a high of 60-80% for irbesartan); food does not influence the bioavailability, except for valsartan (a reduction of 40-50%) and eprosartan (increase). A limited dose-peak plasma levels/areas under the plasma level-time curve proportionality is observed for some of the ARBs. Most of these drugs have high plasma protein binding (95-100%); irbesartan has the lowest binding among the group (90%). The steady-state volumes of distribution vary from a low of 9 L (candesartan) to a high of 500 L (telmisartan). (ABSTRACT TRUNCATE
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PMID:Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. 1085 85


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