Gene/Protein Disease Symptom Drug Enzyme Compound
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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several necropsy reports have suggested that cerebral vascular disease (CVD) is more frequent in HIV positive patients than in HIV negative individuals of the same age, although clinical signs are rare. We describe three patients for whom CVD was the clinical manifestation that led to diagnoses of HIV infection. The patients were two men and a woman aged 29, 52 and 66, respectively, with differing risk factors for CVD: smoking (3), blood hypertension (2), endocarditis (1) and free protein S deficiency (1). The risk factors for HIV infection were also different. The CVD diagnoses were confirmed by computed tomography, which revealed lacunar infarction in two cases with favorable outcomes and embolia-like infarction with subarachnoid hemorrhage in the third patient, who died a few days later. CD4 levels varied (50, 130 and 689/mm3). Our observations lead us to the following conclusions: 1) CVD can be a first clinical manifestation of HIV infection and the disease that allows seropositivity to be diagnosed. Although CVD usually presents in advanced stages of HIV infection, it can also occur in seropositive patients who do not meet the criteria for AIDS. 2) The classical risk factors for vascular disease probably play a dominant role in the etiology of CVD in such patients, alongside systemic complications related to the virus; the direct role of HIV remains to be determined. 3) AIDS should be considered and ruled out in patients with CVD who are at risk for HIV infection, even in older patients with vascular risk factors.
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PMID:[Cerebrovascular disease as a form of presentation of HIV infection]. 900 48

Biochemical and clinical markers are critical for efficient development of new molecular entities. Biologic markers of drug effect, sometimes referred to as "surrogate" markers, are used when such clinical outcome measures as survival are substantially delayed relative to predictive biochemical changes or clinical effects of the new molecular entity. Biologic markers have generally been used for early-phase decision-making studies and accelerated regulatory approvals for much-needed drugs to treat cancer and acquired immune deficiency syndrome (AIDS). The rationale for these two uses of biologic markers is different and therefore the foundation required for establishing and validating each may be different. The theoretical foundation required for a marker that will be used to justify the regulatory approval of a treatment for a life-threatening disease should be greater than the required for an early decision-making study with an angiotensin II antagonist that will be used to treat mild to moderate hypertension. Use of CD4 counts as "surrogate markers" for prolonged survival was inappropriate. In contrast, changes in angiotensin-II concentrations and other renin-angiotensin system biochemical markers, observed for the first time in a study in humans, with a purported angiotensin-II receptor antagonist indicate that the new molecular entity is working as hoped. This is a good decision-making tool, because theory indicates that these changes should lead to reduced blood pressure, which is a predictive "surrogate" for reduction in subsequent cardiovascular events. Surrogate, biologic markers should be used only if they have a rational theoretical basis, are proven in preclinical or clinical experience, and are measured with validated methods. Different validation-acceptance criteria for decision-making markers compared with markers used for regulatory approval must be prospectively acknowledged and delineated.
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PMID:Selecting and validating biologic markers for drug development. 915 68

The major women's health issues in the English-speaking Caribbean (e.g., sexually transmitted diseases [STDs], domestic violence, abortion, adolescent pregnancy, cancer, hypertension, and diabetes) now resemble those in the US. In the Caribbean, however, these health problems are rooted in unique cultural, socioeconomic, and environmental contexts that affect their resolution. For example, as a result of poverty and their low social status, women in the Caribbean are relatively powerless in sexual decision making and disadvantaged in terms of protecting themselves against AIDS, other STDs, and unwanted pregnancy. Caribbean-trained physicians directly influence the quality of women's health in the West Indies. Their medical school education affects their diagnostic and interpersonal skills in clinical practice and the ethical values that form the basis of policy making. The University of West Indies (UWI) Faculty of Medicine trains students from 20 English-speaking Caribbean islands at 3 campuses. During 1990-91, 438 male and 350 female medical students were enrolled. The relatively high female enrollment reflects the fact that Caribbean doctors are poorly paid and not highly esteemed, making the field more open to women. However, only 3 of the 31 full professors in the UWI medical faculty are women. Gender bias further hinders the ability of female physicians to form the professional relationships necessary for advancement. Medical education should include training on interpersonal skills, gender issues, and biomedical ethics. More female role models in medical education and female policy makers would substantially alter the scope and effectiveness of reproductive health programs.
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PMID:Medical education, women's status, and medical issues' effect on women's health in the Caribbean. 928 64

The development and evaluation of new drugs often rely on surrogacy. An intermediate outcome becomes a surrogate outcome if it fulfils certain criteria, it should be easier to measure compared with the clinical outcome, a statistical relationship should exist between the clinical outcome and the surrogate outcome, a relation should exist allowing prediction of the degree of clinical effect based on the measured effect on the surrogate outcome. Development and authorization of drugs today often rely on so-called surrogate outcomes. Is this use sound? The validity of such outcomes has been reviewed in different therapeutic areas: hypertension, venous thromboembolism, AIDS, osteoporosis, hepatitis C. Based on this review, a pragmatic strategy is proposed which allows for the validation and proper use of surrogate outcomes.
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PMID:[Clinical evaluation: from intermediate to surrogate criteria]. 943 78

In this article, we describe pulmonary hypertension in two men (31 and 43 years of age) with human immunodeficiency virus (HIV) infection who were examined at Mayo Clinic Rochester. Among 88 reported cases (including the two current ones) of HIV- or acquired immunodeficiency syndrome (AIDS)-associated pulmonary hypertension, 61% were male; the age range was 2 to 56 years (mean, 32). Dyspnea was the usual initial symptom. Of the 74 patients in whom pulmonary artery pressure was recorded or calculated by echocardiography, systolic pressures ranged from 49 to 118 mm Hg (mean, 68). Of the 33 cases in which lung tissue was evaluated microscopically, 28 (85%) were of the plexogenic variant of pulmonary arterial hypertension. Of the other five cases examined histologically, three consisted of thrombotic pulmonary arteriopathy (one was due to recurrent thromboembolism, and the other two were due to in situ thrombosis), and two were of pulmonary venoocclusive disease. No correlation existed between either CD4 counts or a history of pulmonary infections and the development of pulmonary hypertension. In 15 of the 88 patients (17%), confounding factors for hypertensive pulmonary vascular disease were present, including coexisting liver disease in 13 and coagulation abnormalities in 2. In 83% of the patients, the development of pulmonary hypertension seems to have been related primarily to the chronic HIV infection. Pulmonary hypertension was more rapidly progressive in patients with HIV or AIDS than in those with primary pulmonary hypertension; the reported time intervals between onset of symptoms and diagnosis were 6 months and 30 months, respectively. The 1-year survival rate for patients with HIV and pulmonary hypertension was 51%, based on the follow-up data compiled from the 63 patients in whom it was described; this compares with a 1-year survival rate of 68% for patients with primary pulmonary hypertension. Death was considered a direct consequence of pulmonary hypertension in 29 (76%) of the 38 fatal cases.
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PMID:Human immunodeficiency virus infection and pulmonary hypertension: two new cases and a review of 86 reported cases. 944 76

Hemodialysis vascular access-related problems account for most hospitalizations in chronic hemodialysis patients. Although some co-morbid risk factors for early fistula failures have been described, a great deal of unknown exists as to why access survival is favorable in some patients. In this longitudinal study, fistulae patency and thrombosis episodes were monitored from placement date in three groups of end-stage renal disease (ESRD) patients who have been on dialysis for > or =90 days. Thirty-six patients (29 male; 80%) with a mean age of 42+/-2 years were monitored. The groups consisted of eight patients with biopsy-confirmed focal segmental glomeruloscierosis (FSGS), 13 with acquired immunodeficiency syndrome-related nephropathy (human immunodeficiency virus [HIV]), and 15 with hypertensive ESRD (hypertensive nephrosclerosis [HTN]) who served as controls. Diabetics and patients aged > or =64 years were excluded. Twenty-five of 36 (69%) fistulae were prosthetic (AVG), while 11 (31%) were native (AVF). The FSGS group was more likely to have an AVG (87.5%), while 54% of the HIV group had an AVG. The thrombosis event rate was significantly greater among the FSGS patients (3/patient-year) than the HIV (0.15/patient-year) and HTN (0.5/patient-year) patients (P < 0.0001 and P < 0.002, respectively). The mean thrombosis-free duration for both AVG and AVF among the HIV and HTN groups were 318.5+/-17 days and 311.7+/-22.5 days, respectively. These were significantly greater than in the FSGS group (26.5+/-7 days; P < 0.0001). The cumulative 1-year patency rate for AVG among the HIV and HTN groups was 85% and 65%, respectively, while that of the FSGS group was 0%. Kaplan-Meier hazard analysis showed that all groups were at risk of access thrombosis as time progressed, but the FSGS group had the highest risk of access thrombosis, which began from the date of placement and increased exponentially with time. The increased thrombosis rate among the patients in the FSGS group correlated with their weight (R = 0.8, P = 0.003) and pre-ESRD 24-hour urinary protein excretion (R = 0.9, P = 0.001). The HIV status appeared to confer enhanced hemodialysis access survival. This may be related to the high rate of native fistulae placement and favorable vascular reactivity to shear stress. Accelerated atherosclerosis and small caliber vessels may be responsible for the poor fistulae outcome among the FSGS group. More studies will be necessary to further explore these findings.
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PMID:Hemodialysis vascular access: variable thrombus-free survival in three subpopulations of black patients. 946 95

The decision to use any pharmacologic intervention inevitably rests on balancing the efficacy and safety of the intervention. The advent of the acquired immunodeficiency syndrome epidemic greatly increased awareness of transfusion-related illnesses and focused attention on methods to prevent the need for blood and blood products. This has led, especially in the last decade, to increased use of drugs to help reduce perioperative bleeding. This chapter focuses on the lysine analogues and aprotinin as the serine protease inhibitor currently available in clinical practice. Both groups of compounds have recently shown promise in reducing surgical bleeding. However, the reader will notice that none of these agents are new; they have all been available for more than 30 years. What is new is their use in preventing bleeding. We therefore have considerable knowledge regarding the safety of these compounds. The first part of this review will compare the actions of these two types of agents on the processes related to thrombosis, hemostasis, and fibrinolysis. This is followed by a comparison of the efficacy of each intervention and any dose-response relationship. This section highlights the reported reduction in postoperative bleeding with both classes of agent. There is, however, no obvious or consistent reduction in the transfusion of blood and blood products in patients given lysine analogues. In contrast, there is a consistent reduction in the need for blood transfusions in patients given aprotinin therapy. The next major section will discuss the evidence to suggest that these drugs may, because of their known effects on the processes related to inflammation, hemostasis, and cellular repair, contribute to an improvement or worsening of outcome after cardiac operations. In particular, this section focuses on the antiinflammatory actions and modifications in vascular tone associated with aprotinin therapy. These effects may be related to improved outcome in patients by reducing the incidence of permanent neurologic deficit or stroke after heart operations, as well as inhibiting pulmonary vascular hyperreactivity and hypertension in susceptible individuals. Finally, this brief review discusses the safety issues that have been raised in regard to each of these classes of agents, specifically problems associated with abnormal renal function, hypersensitivity reactions, and thrombotic complications.
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PMID:Aprotinin versus lysine analogues: the debate continues. 956 97

In this article, as part of an evaluation of the future of medical education in California, we characterize the distribution of disease and injury in California; identify major factors that affect the epidemiology of disease and injury in California, and project the burden of disease and injury for California's population to the year 2007. Our goal is to elucidate the major causes of illness and disability at present and in the near future in order to focus state resources on the interventions likely to have the greatest impact. Data from various governmental agencies were utilized; the base year, 1993, is the most recent year with sufficient information available when this report was prepared. Several major risk factors have decreased, including smoking (30% decline from 1984 to 1993) and drinking and driving. However, hypertension prevalence has not changed, and overweight has increased dramatically. Poverty continues to burden about 15% of Californians, with poverty highest among children. During 1993, 220,271 Californians died, with 3 major causes accounting for 61% of these deaths: coronary heart disease (31%), cancer (23%), and stroke (7%). In terms of potential years of life lost (years lost before age 65), the most important causes of death in 1993 were unintentional injury (756 years lost/100,000 population), cancer (632 years), and the acquired immunodeficiency syndrome (AIDS; 491 years). Mortality rates were highest among blacks and lowest among Asians. Overall mortality in California has been declining for decades; in just 1 decade, from 1980 to 1991, mortality declined from 780 to 680 deaths per 100,000 population. Several major causes of death have declined, including coronary heart disease, stroke, unintentional injury, cirrhosis, and suicide, while others have increased, for example, chronic obstructive lung disease and diabetes mellitus. Death from AIDS increased dramatically in the past decade, but is leveling off, and death from cancer is beginning to decline. Rates for overall mortality and morbidity, and for most specific conditions, should continue to decline. A projected 28% population increase by 2007 will yield a corresponding increase in the absolute level of disease cases and death; a disproportionate increase in younger and older groups will yield increased conditions affecting young (unintentional injury, AIDS) and older (heart disease, cancer, stroke, diabetes mellitus) people. Californians should experience overall improved health in coming years, reaping benefits of reduced environmental and behavioral risk factors as well as improved medical treatment and rehabilitation. Coordinated strategies for health promotion, disease prevention, delivery of medical treatment, and rehabilitation are needed to maintain and improve present levels of health across the life span.
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PMID:Disease and injury in California with projections to the year 2007. Implications for medical education. 961 96

Postmortem examination of the lungs of a patient with advanced AIDS who had developed pulmonary arterial hypertension late in the course of the illness demonstrated extensive cytomegalovirus (CMV) infection in endothelial cells of the lung microvasculature. Enlarged CMV-infected endothelial cells were present in virtually all histologic sections of the lungs, protruded into and compromised the lumens of the small vessels they lined, and were estimated by image cytometry of immunohistochemically stained sections to comprise 0.8% of the total lung tissue volume. Comparison with experimental microvascular embolization studies suggests that this amount of compromise of the microvascular luminal area of the lung is sufficient to elevate pulmonary arterial pressure significantly. Pathologic features in this case differed from both the plexogenic arteriopathy seen in previously reported cases of AIDS-associated primary pulmonary hypertension and the usual form of CMV pneumonitis in AIDS in which alveolar epithelial cells are the predominant site of infection.
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PMID:Microvascular cytomegalovirus endothelialitis of the lung: a possible cause of secondary pulmonary hypertension in a patient with AIDS. 967 94

We report 8 patients with the acquired immunodeficiency syndrome (AIDS) and intracerebral haemorrhage. There were 7 men and 1 woman (mean age 37.2 years) with a mean CD4 count of 81.2/mm3. Alcohol abuse was recorded in 7 patients, intravenous drug use in 4, homosexual activity in 2, thrombocytopaenia in 1 and severe hypertension in 1. There were 5 lobar and 3 deep haemorrhages. Potential aetiologies of intracerebral haemorrhage included cerebral toxoplasmosis (n = 2), thrombocytopenia (n = 2), hypertension (n = 1) and cerebral tuberculosis (n = 1). Data of these patients were compared with those of 30 AIDS inpatients without brain haemorrhage matched by age and sex and no statistically significant differences in risk factors for AIDS except for alcohol abuse (> 80 g/day) (p = 0.045) were found. Causes of brain haemorrhage in AIDS patients are heterogeneous. The relationship between both conditions may be explained by the effect of several predisposing factors to stroke in association with AIDS-related complications. Intracerebral haemorrhage is a late and serious complication of AIDS (mortality 62.5%). The frequency of intracerebral haemorrhage in AIDS (1.0%) is higher than that expected in a general population of young adults.
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PMID:Intracerebral haemorrhage in AIDS. 968 62


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