Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies of human immunodeficiency virus type 1 (HIV-1) encephalitis have shown that in addition to well established white matter damage, the neocortex shows thinning, loss of large neurons and dendritic damage. In order to identify neuronal populations affected in HIV encephalitis and to determine how neuronal damage relates to the severity of HIV infection within the nervous system, we quantified parvalbumin (PV+) and neurofilament (NF+) immunoreactive neurons in the frontal cortex and hippocampus. We found that in the neocortex, the density of NF+ and PV+ neurons was independent of severity of HIV encephalitis, and therefore changes in these neuronal subsets did not account for previously reported neuronal loss. However, neuritic processes of PV+ neurons were fragmented, atrophic and in some cases distended. In contrast to the frontal cortex, there was a trend toward decreased density of PV+ neurons in the hippocampus which only reached significance in the CA3 layer where there was a 50-90% decrease in PV+ neurons. This decrease was closely correlated with the severity of HIV encephalitis. Double-label immunocytochemical analysis confirmed neuritic damage to interneurons. These results suggest that HIV encephalitis differentially involves specific subpopulations of neurons. Since direct HIV infection of neuronal cells was not detected, damage to PV+ cells and fibers may be indirectly mediated by cytokines released by HIV-infected microglia.
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PMID:Selective neuronal vulnerability in HIV encephalitis. 148 89

RU-486 or mifepristone is best known as an antiprogestin and an abortifacient, but it has broad medical applicability. The drug is also a potent blocker of corticosteroid receptors, and it has shown promise in the treatment of breast cancer, inoperable meningioma, and cushing's disease. Cushing's is a model for the symptomatology of aging which may involve enhanced response to corticosteroid. RU-486 has reversed the osteoporosis, thinning of skin, muscle atrophy, obesity, adult onset diabetes, depression, hypertension, and immunosuppression associated with this disease. RU-486 may be of value in aiding cervical dilation, lactation, and the treatment of endometriosis. In addition, breast, bowel, kidney tumors, hepatomas, endometrial cancer, and fibrosarcomas can show corticosteroid dependency, suggesting that RU-486 may have clinical value against inoperable tumors. In a preliminary 1987 phase I study, in estrogen-positive, chemotherapy-refractory breast cancer patients in Montpelier, France, Ru-486 produced objective tumor regression (6 of 22) that was prolonged (3 months) in 4 patients. Clinical relief of bone pain was observed in 7 of 23 patients with a decline in carcinoembryonic antigen (CEA) tumor makers in 8 patients. Growing in vitro data also show that RU-486 can directly inhibit breast cancer cell proliferation. RU-486 has application for HIV infection, based on data that there is a serum factor in AIDS patients that enhances corticosteroid lympholysis. IN addition, the immune restorative action of RU-486 suggests that it could counteract the immunosuppression seen in aging, in cancer, or in viral or stress-related disease, which has recently focused clinical attention on its potential in the treatment of senile dementia and depression. Scientific conferences and workshops are needed to alert scientists, physicians, and the public to the potential medical benefits of this drug.
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PMID:RU 486: how abortion politics have impacted on a potentially useful drug of broad medical application. 150 96

Clinical and pathological evidence of subcortical central nervous system (CNS) damage is observed commonly in patients with human immunodeficiency virus (HIV) encephalitis. Whether other CNS regions are also affected has not been well studied. We report neocortical damage in patients with HIV encephalitis. Using quantitative techniques, we demonstrate statistically significant thinning of the neocortex, with a loss of large cortical neurons. Qualitative and quantitative assessments of neocortical neuropil reveal a loss of synaptic density and vacuolation of dendritic processes. Failure to demonstrate an association of these changes with the presence of HIV antigens suggests that neocortical damage may be an indirect effect of HIV infection of the CNS.
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PMID:Neocortical damage during HIV infection. 190 52

Acquired immunodeficiency syndrome (AIDS) is a systemic illness affecting multiple organs, including the heart. Left ventricular (LV) diastolic dysfunction has been reported as the first echocardiographically detectable abnormality in several cardiovascular disorders. We tested the hypothesis that Human Immunodeficiency Virus (HIV) carriers have LV diastolic impairment when studied early in the clinical course of the infection. Doppler echocardiographic and computerized time-motion parameters of LV diastolic function were obtained in 51 HIV patients and in 25 age- and sex-matched healthy controls. The HIV population consisted of 28 totally asymptomatic subjects and 23 patients with incipient AIDS. As compared to controls, the HIV group had similar heart rate, blood pressure level, LV dimensions and fractional shortening, but increased isovolumetric relaxation time (P = 0.03), early filling duration (P < 0.001) and decreased early mitral flow peak velocity (E) (P = 0.02) and EF slope (P < 0.001). HIV patients also showed lower values for posterior wall thinning (PWT, P < 0.01) and peak lengthening velocity of the posterior wall (PVL, P < 0.05), and a trend to a decreased peak rate of LV enlargement in diastole (D+, P = 0.05). Doppler-derived parameters of diastolic function were significantly altered in the asymptomatic HIV group vs controls. The LV diastolic indices were similar in symptomatic and asymptomatic HIV patients except for PWT, which was lower in the symptomatic HIV group (P = 0.04). Since mild and focal wall motion abnormalities were detected in 11 HIV carriers (22%), comparison of LV diastolic indexes between HIV patients and controls was also performed in two subgroups; these included asymptomatic (n = 26) and symptomatic (n = 14) patients with normal contractile state. The two subgroups had abnormalities of diastolic function similar to those of the HIV group as a whole, but with somewhat lower levels of statistical significance. Our data strongly suggest that there is myocardial involvement at the early stage of HIV infection; however, its impact on the clinical course of the disease remains to be clarified.
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PMID:Left ventricular diastolic function in asymptomatic and symptomatic human immunodeficiency virus carriers: an echocardiographic study. 773 24

Until recently, some behaviors were viewed as entailing a high risk of HIV infection, but HIV is now considered a great risk for the female population in general. The number of HIV infected women is increasing rapidly even in areas such as Mexico and South America where women form a minority of AIDS patients. Most women infected with HIV and other sexually transmitted diseases (STDs) are sexually active and at risk of pregnancy. Some STDs, notably those producing genital ulcers, increase the risk of HIV infection. It is not yet known whether STDs not producing ulcers also increase the risk. There is controversy over the extent to which specific contraceptive methods increase or perhaps reduce the risk of HIV infection. Some unconfirmed assumptions are that the cervical ectopy produced by oral contraceptives (OCs) results in affected zones more vulnerable to trauma and thus perhaps to HIV infection, and that combined OCs by reducing menstrual bleeding also reduce risk of infection. OCs containing only progestins may increase the risk of transmission by inducing irregular bleeding, thickening the cervical mucus, and thinning the vaginal epithelium. Injectables may increase risk by increasing bleeding, thinning the vaginal epithelium, or through use of contaminated needles in application. IUDs may increase menstrual bleeding and are not advisable in any event for women at high risk of other STDS. Condoms and spermicides offer some protection against STDs, but are not highly effective contraceptives. The interrelations between risk of pregnancy and of disease are a great and largely unresolved problem in women's reproductive health. Few family planning services are able to address prevention of STDs and especially AIDS adequately. Methodological and logistical problems impede study of the interrelations between contraception and STDs, and resources are limited. Studies of commercial sex workers in different countries have offered a partial solution. Women's lack of power to negotiate successfully concerning sexual relations and their lack of access to a means of preventing STDs under their own control are factors in their vulnerability. Improved reproductive health of women will require development of new products to control disease, structural changes in health services, and continued research.
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PMID:[Contraceptives, HIV, and other sexually transmitted diseases]. 789 58

The current literature on the transmission of HIV and the use of oral contraceptives (OCs), injectables, IUDs, spermicides, and the female condom was reviewed. Some of the methodological difficulties involved study design (observational studies, cross-sectional, case control, and prospective studies) and confounding factors (age, marital status, sexual partners). The impact of OC use on HIV transmission is likely to be minor, but some factors contributing to transmission include cervical ectropion, which enhances HIV transmission. Nevertheless, in a 1990 Nairobi study of 4404 women no such association was detected. Sexually transmitted diseases (STDs) have been risk factors in HIV transmission. OCs that decrease irregular bleeding may protect against HIV. Progestin-only pills could act on the risk of HIV transmission by thickening cervical mucus and thinning the vaginal epithelial layer. 21 epidemiological studies were identified on the use of OCs and transmission. Except for a 1990 Nairobi study among prostitutes none of them reported a significant association between OC use and HIV seropositivity. Injectables (Depo Provera) could theoretically increase HIV transmission, but no such conclusive evidence has surfaced. Increased risk of transmission or seropositivity has been reported with IUD use, but this needs confirmation by prospective studies. Among spermicides the nonoxynol-9 sponge slightly increased HIV seroconversion in 139 sex workers in Nairobi in a 1992 study. However, this trial was contradicted by other prospective studies conducted in Cameroon and Zambia. Nonoxynol-9 kills HIV but also damages the cervical and vaginal mucosa enhancing HIV transmission. In 1992 in vitro activity in 26 out of 131 other spermicides screened inhibited HIV. The female condom was tested in 104 women in a 1993 prospective study in the US and no recurrences of trichomonas occurred in 20 women who used it consistently over a 6-week period. More prospective epidemiological studies are needed, and the risk of HIV infection should be part of counseling on contraceptives.
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PMID:Contraceptive methods and the transmission of HIV: implications for family planning. 820 68

The microvasculature of the cerebral cortex in AIDS brains was investigated by means of stereology at the light and electron microscopic levels. Stereologic parameters for microvessels were determined in formalin-fixed autopsy tissue of 24 AIDS patients and of 35 age- and sex-matched controls. At the light microscopic level these encompassed the measurement of the diameter, volume fraction, surface area density, and length density; at the electron microscopic level profile area, perimeter, diameter of capillaries, endothelial cells, pericytes, and basal lamina as well as the mean thickness of the basal lamina were measured. In AIDS brains a significant increase in the diameter of cortical vessels was noted. The surface area density (Sv) and volume fraction (Vv) of microvessels were likewise significantly increased in AIDS brains. No changes were noted for the length density (Lv) which also indicates that no changes in the number of vessels occur in HIV-1 infection. Ultrastructural thinning of the basal lamina was a consistent finding. Vacuoles occurred in the basal lamina of capillaries and increased in number and size in AIDS brains. Using morphometric methods, significant changes of cortical vessels are detectable at the light and electron microscopic level. These changes most probably represent the morphological substrate of an altered blood-brain-barrier in AIDS brains and may account for the reported hypoperfusion demonstrated in SPECT analyses.
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PMID:Vascular changes in the cerebral cortex in HIV-1 infection: I. A morphometric investigation by light and electron microscopy. 893 85

In three patients, a 36-year-old HIV seropositive homosexual man and two women aged 35 and 59 years who had acquired HIV infection through heterosexual contact, signs of lipodystrophy developed after prolonged anti-HIV triple therapy. The observed syndrome is seen after prolonged use of HIV protease inhibitors: it is characterized by peripheral fat wasting, central fat accumulation, hyperlipidaemia and insulin resistance. Typically the subcutaneous fatty tissue disappears resulting in prominent zygomata, veins and muscles and thinning of extremities and buttocks. In addition to abdominal fat accumulation, there have been reports on the occurrence of a dorsocervical fat pad, the so-called buffalo hump. Lipodystrophy caused by protease inhibitors is a risk factor for cardiovascular disease. Recognition of the syndrome is essential for adequate follow-up and possible treatment.
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PMID:[Lipodystrophy and 'buffalo hump' during treatment with HIV protease inhibitors]. 1006 60

Lipodystrophies, characterized by reduction of subcutaneous fat over part or all of the body surface, are uncommon. Their causes are unknown. Recently, lipodystrophy has been reported in human immunodeficiency virus (HIV)-infected patients taking protease inhibitors, which have been recommended since 1996 as standard therapy for HIV disease in combination with nucleoside analogues. In these cases, lipodystrophy consists of an association of peripheral lipoatrophy with central adiposity. We report four HIV-infected men on protease inhibitors who developed a disfiguring lipodystrophy. In three of them, the protease inhibitor was administered for a mean duration of 21.5 months (range 19-23) with good immunological and virological responses. Patient 4 had been treated for 2 years with successive combinations of protease inhibitors with nucleoside analogues without success. The four patients progressively developed an increase in abdominal girth associated with fat wasting of the face and legs. Two of them had recurrent paronychia of the great toes. Triglyceride levels were moderately increased in all patients, and one had a slightly increased cholesterol level. One patient had elevated glucose and insulin plasma levels during a glucose tolerance test. In two patients, a deep biopsy taken from the thigh showed thinning of the subcutaneous fat without other morphological changes. Computed tomographic scans of the face and abdomen confirmed the loss of almost all subcutaneous fat of the cheek and temporal regions, and abdominal perivisceral fat accumulation. For patients 1-3, the protease inhibitor was replaced by a non-nucleoside reverse transcriptase inhibitor. Nine months later, dysmorphic changes had not regressed, but lipid abnormalities had returned to normal and the paronychia had disappeared.
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PMID:Lipodystrophy associated with protease inhibitors. 1073 57

(1) Disturbing changes in body fat distribution started to be described in 1997 in HIV-infected patients treated with antiretroviral drugs, with fat accumulation at various levels of the trunk, and thinning of the limbs, buttocks and face. (2) The vast majority of cases occurred in patients on HIV protease inhibitors. (3) The long-term clinical consequences are unknown.
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PMID:Fat distribution and HIV protease inhibitors. 1084 64


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