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)

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

There have been reports of adrenal failure in patients treated with suramin, an agent that has recently been used as therapy for acquired immune deficiency syndrome. We conducted this study to assess the effect of suramin on adrenal function and structure in a primate, the cynomolgus monkey. Five male monkeys were treated with suramin (800 mg/m2, im) once a week, for 5 weeks. Five other animals (controls) received saline. The treated animals had progressive elevations of plasma ACTH (P less than 0.05) and PRA (P less than 0.02) and decreased serum cortisol responses 30 min after the administration of synthetic ACTH (P less than 0.05) compared to controls. There was disruption of the architecture of the adrenal cortex, a diffuse inflammatory cell infiltrate, and thinning of the zona glomerulosa and zona fasciculata in the suramin-treated animals. We conclude that suramin is toxic to adrenal cortical tissue and might be useful in treating conditions with adrenal cortical hyperfunction, such as adrenal cortical carcinoma and Cushing's syndrome.
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PMID:Effects of suramin on the function and structure of the adrenal cortex in the cynomolgus monkey. 303 53

Few data are available about cardiac involvement in AIDS. We examined 102 consecutive patients with AIDS diagnosed clinically and serologically (Walter Reed Stage 5 and 6), by means of TM and cross-sectional echocardiography with the aim of detecting cardiac abnormalities. None of the patients had overt clinical signs of heart failure. Fifty-five (54%) patients showed persistent tachycardia, diminished left ventricular (LV) wall thickness (mean 7.6 +/- 0.2 mm) and decreased percentage LV fractional shortening (27 +/- 5). In 42 (41%) there was a globular and poorly contracting LV. Thirty-nine (38%) patients had pericardial effusion which was moderate in 30 and small in nine. In four patients, valvular endocarditic vegetation was shown--on the tricuspid valve in three, on the aortic valve in one: all of them were drug addicts; in three (2.9%) patients a cardiac mass was found which proved to be a localization of Kaposi's sarcoma in two. Twenty-five (24.5%) patients died; necropsy showed cardiac chamber dilation, and thin LV walls in 18. On microscopic examination, myocardial fibrosis and lymphocyte infiltration with cell necrosis were observed. We conclude that cardiac abnormalities are common in AIDS. Impairment in LV contractility as assessed from fractional shortening appears to be the most common echocardiographic finding, followed by LV wall thinning, pericardial effusion and eventually by LV cavity dilation. This evolution is suggestive of myocardial damage and supports the hypothesis that dilated cardiomyopathy may be a cardiac complication of AIDS.
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PMID:Echocardiography detects myocardial damage in AIDS: prospective study in 102 patients. 318 Nov 75

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

A case of proximal subungual onychomycosis due to Microsporum canis in a 36-year-old woman is presented. The onychomycosis involved the left thumb and the little fingernails, with thinning of the nail plate and crumbling of the nail plate surface. A milky-white discoloration of the proximal portion of the left thumbnail was also evident. A 2-mm longitudinal nail biopsy showed a large number of fungal elements in the whole length of the nail plate. Fungal hyphae were more numerous in the ventral nail plate and produced detachment of the superficial nail plate. The nail bed was not invaded by fungal elements and was devoid of inflammatory changes. Proximal subungual onychomycosis is uncommon in immunocompetent individuals but has frequently been described in patients with AIDS. In our patient, in whom the proximal subungual onychomycosis was due to M. canis, there were no clinical or biochemical signs of immunodeficiency. Oral treatment with terbinafine, 250 mg/daily for 2 months, produced clinical and mycological cure.
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PMID:Proximal subungual onychomycosis due to Microsporum canis. 874 10

In human immunodeficiency virus 1 (HIV-1)-infected patients, a hypoperfusion is seen by SPECT analyses in different brain regions but a specific pattern for the predominance of a specific brain region has not been found. The vessels of the cerebral cortex of the frontal, temporal, parietal, and occipital lobes of acquired immunodeficiency syndrome (AIDS) brains and control brains were analyzed by immunohistochemistry and lectin histochemistry. Immunohistochemistry was performed for collagen IV, laminin (basal lamina), and factor VIII (endothelial cell) and lectin histochemistry [Ricinus communis agglutinin (RCA-I), Ulex europaeus agglutinin (UEA-I), wheatgerm agglutinin (WGA) and soybean agglutinin (SBA)] was used to study changes of glycoproteins in the endothelial cell membrane. Vessels were counted in the gray and white matter, and their staining intensity for the different antibodies and lectins was rated using a three-point scale. Immunoreactivity for collagen IV was reduced in AIDS brains, which may be related to thinning of the basal lamina of cerebral vessels, as has previously been shown by electron microscopy. Lectin histochemistry with SBA, UEA-I and WGA indicated loss of glycoproteins in the membrane of endothelial cells. The data from the present study show morphological changes of the endothelial cells and of the basal lamina in the brain of individuals with AIDS, and might represent the morphological sequelae of a disturbed blood-brain barrier, or may account for the hypoperfusion seen in SPECT analyses.
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PMID:Vascular changes in the cerebral cortex in HIV-1 infection. II. An immunohistochemical and lectinhistochemical investigation. 881 Nov 23

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

The objective of this study was to determine whether progestin-only contraceptives induce thinning of the vaginal epithelium in nonhuman primates. Eight intact rhesus monkeys (four per group) were treated with either a single intramuscular injection of 30 mg of Depo-Provera or a subcutaneous insertion of Norplant-II (2 x 75 mg rods; day 0). Norplant-II rods were removed 90 days after insertion. Vaginal biopsies were obtained during a pretreatment menstrual cycle and following treatment on days 10, 30, 60, 118, and 146. Formalin-fixed vaginal biopsies were evaluated for epithelial thickness and the degree of keratinization. The circulating levels of estradiol, progesterone, medroxyprogesterone acetate (MPA), or levonorgestrel (LNG) were monitored throughout the study by specific radioimmunoassays. Circulating levels of estradiol and progesterone confirmed the stage of the menstrual cycle in which pretreatment biopsies were obtained. Following treatment with Depo-Provera, serum levels of MPA increased to 2.3 +/- 0.6 ng/ml (x +/- SE, n = 4) within 24 hr. Serum levels of MPA were maximal on day 14 (5.5 +/- 0.9 ng/ml), dropped below 1 ng/ml by day 50, and were nondetectable by day 70. Circulating levels of LNG were elevated 24 hr after insertion of Norplant-II (5.8 +/- 3.0 ng/ml), peaked on day 2 (7.6 +/- 4.2 ng/ml), remained between 1.4 and 6.2 ng/ml from days 14 to 90, and were nondetectable by day 118, the first serum sample after removal of Norplant-II. There were no significant differences (p > 0.05) in the epithelial thickness (microm), number of epithelial cell layers, or type of epithelium present in vaginal biopsies obtained during the follicular or luteal phases of the pretreatment menstrual cycle. Conversely, a pronounced effect of progestin treatment was observed on the vaginal epithelium. There were no significant differences (p > 0.05) between the two progestin treatment groups, but a significant effect (p < 0.05) over time was observed (two-way ANOVA). Compared with pretreatment menstrual cycle controls, the vaginal epithelial thickness was decreased (p < 0.05) by day 30 or 60 following Norplant-II insertion or Depo-Provera injection, respectively. The number of epithelial cell layers was also decreased (p < 0.05) on days 30 and/or 60 in progestin-treated monkeys compared with pretreatment control cycles. Following removal of Norplant-II or metabolic excretion of MPA, the vaginal epithellium regenerated and the thickness was no longer different (p > 0.05) from the pretreatment control cycle. These data demonstrate that progestin-only contraceptives induced thinning of the vaginal epithelium in rhesus monkeys, and this effect was rapidly reversible following physical or metabolic removal of the progestin.
AIDS Res Hum Retroviruses 1998 Apr
PMID:Effects of two progestin-only contraceptives, Depo-Provera and Norplant-II, on the vaginal epithelium of rhesus monkeys. 958 96

Zidovudine (AZT) is currently used to treat human immunodeficiency virus (HIV)-positive women during pregnancy to prevent the prenatal transmission of HIV type 1 (HIV-1). However, AZT not only inhibits HIV replication but also affects the DNA polymerases of human cells; hence AZT is not recommended during the first trimester of pregnancy. The lung is a unique organ because it continues to grow and develop throughout fetal life. Using a human fetal lung organ culture system, we sought to determine the effect of AZT on morphogenesis and epithelial cytodifferentiation of developing alveoli. Lung tissues from three fetuses, 14-15 weeks gestational age, were grown in culture for 24 hours (day 0). AZT at a concentration of either 0.4, 4.0, 8.0, or 40.0 mumol/L was added on days 1, 5, and 10 of growth. The cultures were interrupted on days 6 and 15 and examined by light and electron microscopy for alveolar saccular development, interstitial thinning, and epithelial cell differentiation. On day 6 of growth the treated cultures demonstrated fewer alveolar saccules and a thicker, more cellular interstitium compared to the controls. After 15 days of growth the cultures treated with 0.4 mumol/L of AZT appeared structurally similar to the controls. The cultures treated with AZT concentrations of 4.0 to 40.0 mumol/L appeared unchanged from day 6, implying arrested maturation of the culture. However, epithelial cell differentiation was unaffected. We conclude that AZT at concentrations of 4.0 mumol/L and greater affects the structural development of the human fetal lung in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Pediatr AIDS HIV Infect 1995 Apr
PMID:Effect of zidovudine on human fetal lung development. 1136 85


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