Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
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Ethiopia is a country of 45 million people in northeast Africa. With a stagnant, agriculture-based economy and a per capita gross national product of $110 in 1984, it is one of the world's poorest nations. 70% of the children are mildly to severely malnourished, and 25.7% of children born alive die before the age of 5. Life expectancy is 41 years. The population is growing at the rate of 2.9%/year, but only 2% of the people use birth control. After the 1974 revolution, the socialist government nationalized land and created 20,000 peasant associations and kebeles (urban dwellers' associations), which are the units of local government. The government has set ambitious goals for development in all sectors, including health, but famine, near famine, forced resettlement programs, and civil war have prevented any real progress from being made. The government's approach to health care is based on an emphasis on primary health care and expansion of rural health services, but the Ministry of Health is allocated only 3.5% of the national budget. Ethiopia has 3 medical schools -- at Addis Ababa, Gondar, and the Jimma Institute of Health Sciences. Physicians are government employees but also engage in private practice. A major problem is that a large proportion of medical graduates emigrate. Ethiopia has 87 hospitals with 11,296 beds, which comes to 1 bed per 3734 people. There are 1949 health stations and 141 health centers, but many have no physician, and attrition among health workers is high due to lack of ministerial support. Health care is often dispensed legally or illegally by pharmacists. Overall, there is 1 physician for 57,876 people, but in the southwest and west central Ethiopia 1 physician serves between 200,000 and 300,000 people. In rural areas, where 90% of the population lives, 85% live at least 3 days by foot from a rural health unit. Immunization of 1-year olds against tuberculosis, diphtheria-pertussis-tetanus, poliomyelitis, and measles is 11, 6, 6, and 12% respectively. Infectious diseases dominate the medical scene in Ethiopia. In 1984, tuberculosis accounted for 11.2% of hospital admissions and 12.2% of deaths. The leading cause of childhood mortality in 1984 was diarrhea (45%). Malaria, trypanosomiasis, schistosomiasis, leishmaniasis, and meningococcal meningitis are endemic. Intestinal parasitism is rampant, and the nationwide prevalence of leprosy is 3/1000. Venereal diseases were the 9th most common cause of hospital outpatient visits in 1984, but AIDS is rare. The leading noninfectious diseases are rheumatic and syphilitic heart disease, hypertension, diabetes mellitus, hepatoma, and elephantiasis. Ethiopia has the highest number of cases of nonfilarial elephantiasis -- an estimated 350,000 cases -- in the world. Aside from a large influx of money, the most necessary changes to improve the health system are lowering the salaries of doctors and nurses, reorienting physician training toward primary health care, increasing the quality of existing health services, more efficient management, and better coordination between the Ministry of Health and the voluntary organizations.
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PMID:Health and medical care in Ethiopia. 271 Jan 85

Eight deaths that occurred during Upjohn-sponsored clinical trials of topical minoxidil and two deaths in subjects who used extemporaneous formulations of the drug are summarized. Of the eight patients in clinical trials, five had cardiovascular abnormalities and two had acquired immunodeficiency syndrome-related pneumonia. One patient died of a self-inflicted gunshot wound. One of the subjects who was using extemporaneous topical minoxidil had hypertension and arteriosclerotic disease and the other died of a myocardial infarction. There is little likelihood of significant adverse effects attributable to topical minoxidil because of its low systemic absorption. The evidence suggests that these deaths were the result of causes other than use of the drug.
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PMID:Deaths occurring during clinical studies of topical minoxidil. 354 8

A series of 24 consecutive patients presenting with a fundus picture characterized by a predominance of cotton-wool spots, or a single cotton-wool spot, is reported. Excluded were patients with known diabetes mellitus. Etiologic conditions found included previously undiagnosed diabetes mellitus in five patients, systemic hypertension in five patients, cardiac valvular disease in two patients, radiation retinopathy in two patients, and severe carotid artery obstruction in two patients. Dermatomyositis, systemic lupus erythematosus, polyarteritis nodosa, leukemia, AIDS, Purtscher's retinopathy, metastatic carcinoma, intravenous drug abuse, partial central retinal artery obstruction, and giant cell arteritis were each found in one patient. In only one patient did a systemic workup fail to reveal an underlying cause. The presence of even one cotton-wool spot in an otherwise normal fundus necessitates an investigation to ascertain systemic etiologic factors.
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PMID:Cotton-wool spots. 386 24

Between 1975 and 1983 health care expenditures in Ghana dropped to a low point as a consequence of the structural readjustment program instituted by the World Bank. During 1975-76 only 15% of available funds were spent on primary health care (PHC), which was officially introduced in the late 1970s. PHC made up 20-25% of the health care expenditures by 1991 with about 25% of health personnel engaged in PHC. 2/3 of health care delivery covered urban areas when 60% of the population lived in the countryside. The district of Ejisu-Juaben in the Ashanti region had high morbidity. Tetanus, polio, whooping-cough, and diphtheria had been brought under control, but measles, diarrhea, and malnutrition were still widespread among children under 5 years old. Malaria, bilharzia, intestinal parasites, respiratory infections, hepatitis, anemia, hypertension, and vitamin A deficiency were also grave problems. AIDS was on the rise. Child mortality amounted to 130/1000 live births and maternal mortality to 1400/100,000 cases. The medical structure of the district comprises 10 health posts (6 governmental and 4 mission). Only 72 villages and 120,000 people are cared for. Each post has a mobile team. In 1993 a new community-based health care program began funded by Save the Children Netherlands. In 60 villages a village health committee existed but they were substandard. They were either reactivated or new committees were set up. Training activities were also started in prenatal care, delivery, care of malnutrition and diarrhea, hygiene, and sanitation. Two years later safe motherhood indicators had improved; postnatal care increased from 16% to 49%; medical deliveries increased from 27% to 37%; the share of families with contraceptive acceptance increased from 7% to 21%; and tetanus vaccination among mothers was estimated to have increased from 27% to 86%.
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PMID:[Primary health care in Ghana: no pay no cure?]. 750 Oct 68

Human anti-CD4 IgG antibodies from 3 HIV-1-infected patients were affinity purified and shown to inhibit HIV-1 binding and infection of HBP-T cells. Lymphocytes from patient A, whose anti-CD4 inhibited HIV-1 binding by 68% and infection by 72%, were cultured and transformed with EBV. A human monoclonal antiidiotype antibody against anti-HIV-1 gp120 (2B) was produced, which inhibited infection of HBP-T cells by 68% at 1 microgram/ml. Mice were immunized with 2B to determine whether this anti-CD4 could be an internal image antiidiotype against anti-HIV-1 gp 120 (Ab1). Two mice produced antisera reactive with rgp120 on ELISA, whereas immunization with normal IgG produced minimal reactivity compared to unreactive normal mouse sera. However, immunoblot competition studies in which affinity-purified anti-HIV-1 gp120 (Ab1) bound to the gp120 band on nitrocellulose strips in the presence of 2B demonstrated enhancement of signal (i.e., binding of Ab2 to Ab1), rather than inhibition of Ab1 binding. Thus 2B is not an internal image of the paratope of anti-HIV-1 gp120 but yet it is capable of inducing an antibody against rgp120. This indicates that the anti-CD4 (Ab2) does bind to the binding site of Ab1, but not as a complete internal image. These data indicate the production of a human monoclonal antiidiotype antibody that inhibits binding of HIV-1 to CD4 and induces the production of antibody against HIV-1 gp120, without being an internal image antiidiotype (Ab2 beta).
AIDS Res Hum Retroviruses 1995 Apr
PMID:Production of a human anti-CD4 monoclonal antibody with antiidiotype to anti-HIV type 1 glycoprotein 120. 763 65

The aspartic proteinases are an important family of enzymes associated with several pathological conditions such as hypertension (renin), gastric ulcers (pepsin), neoplastic disease (cathepsins D and E), and AIDS (HIV proteinase). Studies of inhibitor binding are therefore of great importance for design of novel inhibitors for potential therapeutic applications. Numerous X-ray analyses have shown that transition-state isostere inhibitors of aspartic proteinases bind in similar extended conformations in the active-site cleft of the target enzyme. Upon comparison of 21 endothiapepsin inhibitor complexes, the hydrogen bond lengths were found to be shortest where the isostere (P1-P'1) interacts with the enzyme's catalytic aspartate pair. Hydrogen bonds with good geometry also occur at P'2, and more so at P3, where a conserved water molecule is involved in the interactions. Weaker interactions also occur at P2, where the side-chain conformations of the inhibitors appear to be more variable than at the more tightly held positions. At P2 and, to a lesser extent, P3, the side-chain conformations depend intriguingly on interactions with spatially adjacent side chains, namely P'1 and P1, respectively. The tight binding at P1-P'1, P3, and P'2 is also reflected in the larger number of van der Waals contacts and the large decreases in solvent-accessible area at these positions, as well as their low temperature factors. Our analysis substantiates earlier proposals for the locations of protons in the transition-state complex. Aspartate 32 is probably ionized in the complexes, its charge being stabilized by 1, or sometimes 2, hydrogen bonds from the transition-state analogues at P1. The detailed comparison also indicates that the P1 and P2 residues of substrate in the ES complex may be strained by the extensive binding interactions at P3, P'1, and P'2 in a manner that would facilitate hydrolysis of the scissile peptide bond.
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PMID:A structural comparison of 21 inhibitor complexes of the aspartic proteinase from Endothia parasitica. 770 59

Epoetin alfa is a recombinant form of the principal hormone responsible for erythrogenesis, erythropoietin. Already an established treatment for anaemia associated with renal failure, epoetin alfa may also be used to correct anaemia in other patient groups. The drug increases the capacity for autologous blood donation in patients scheduled to undergo surgery and attenuates the decrease in haematocrit often seen in untreated autologous donors. However, transfusion requirements did not significantly decrease in many trials. Epoetin alfa also accelerates red blood cell recovery after allogeneic--but not autologous--bone marrow transplant. Limited data in patients with adult rheumatoid arthritis suggest that while epoetin alfa increases haematocrit/haemoglobin levels, overall clinical rheumatological status may not improve. However, the drug did improve quality of life in a small cohort of children with juvenile rheumatoid arthritis in addition to correcting anaemia. Response rates to treatment with epoetin alfa in patients with anaemia associated with cancer range between 32 and 85%. Anaemia associated with cancer chemotherapy also responds well to treatment with the drug as does anaemia associated with zidovudine therapy in patients with acquired immune deficiency syndrome (AIDS). Studies evaluating the use of epoetin alfa as treatment for anaemia of prematurity have used different methodologies and dosages, making overall analysis difficult. Nevertheless, it appears that high dosages are necessary for response. Results from 1 study suggest that treatment with epoetin alfa appears to be more costly than transfusional support in this application; the relevance of this finding is questionable, however, given that the aim of treatment with epoetin alfa is elimination of transfusion requirements. The incidence of many adverse events associated with epoetin alfa treatment in patients with renal failure (hypertension, seizures and thromboembolic events) has been minimal in patients without renal failure. Adverse events occurred at a similar rate in placebo and epoetin alfa recipients in placebo-controlled trials evaluating the use of the drug as treatment for anaemia in patients with cancer receiving chemotherapy or patients with AIDS receiving zidovudine. In summary, epoetin alfa is an effective alternative to blood transfusion, reducing anaemia and producing consequent improvements in quality of life in many nonrenal applications. It was more effective than placebo in a number of double-blind trials and may be particularly useful as treatment for anaemia associated with other drugs such as cisplatin and zidovudine.
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PMID:Epoetin alfa. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in nonrenal applications. 772 31

Heroin-associated nephropathy (HAN), a complication of intravenous heroin abuse, was initially recognized at Kings County Hospital in Brooklyn, NY, in the early 1970s. Our recent experience indicates that after a steady incidence of new cases of HAN throughout the mid-1980s, a sharp decrease in incidence of new cases occurred starting in 1989. We sought to explore possible explanations for what amounts to disappearance of a previously prevalent disease. By means of retrospective analysis of a hospital-specific registry of new cases of end-stage renal disease (ESRD) at Kings County Hospital in Brooklyn, incidence curves from 1981 through 1993 for new cases of HAN, diabetes-induced renal disease, and human immunodeficiency virus-associated nephropathy were constructed. From hospital computer records, the number of admissions directly related to opioid abuse were extracted and charted. Unpublished surveillance records of the New York State Office of Alcoholism and Substance Abuse Services as well as reports from the New York City Department of Health, Office of AIDS Surveillance and the US Department of Justice Drug Enforcement Administration were used to determine the pattern of change in the prevalence of heroin abuse. Additionally, we used analysis of "street" heroin by the Drug Enforcement Administration to draw curves detailing drug cost and purity in New York City. There were no new cases of ESRD due to HAN for the years 1991 through 1993. The rates for new cases of ESRD due to diabetes and hypertension remained relatively constant throughout this interval.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Disappearance of uremia due to heroin-associated nephropathy. 774 21

A certain number of HIV-infected patients (about 17% in our series) manifest symptoms of cortisol resistance--weakness, weight loss, hypertension, chronic fatigue and intense mucocutaneous melanosis--symptoms which are also typical of Addison's disease. The diagnosis of cortisol resistance is determined through the increased plasma and urinary cortisol values and limited increases in ACTH values. Compared with patients with primary glucocorticoid resistance, AIDS patients have no symptoms of mineral-corticoid or androgen excess, only of glucocorticoid deficiency at target tissues. Mononuclear leukocytes from these patients show receptor changes which consist of an increased receptor number and decreased receptor affinity for glucocorticoids. They also show defective glucocorticoid-induced inhibition of [3H]thymidine incorporation. Glucocorticoid-resistant AIDS patients have a characteristic persistent increase in interferon-alpha production. The inverse correlation between plasma values of interferon-alpha and the receptor affinity for glucocorticoids clearly suggests that interferon production is regulated by the glucocorticoid receptor: the smaller the glucocorticoid effect on lymphocyte cells is, the greater interferon production is. Owing to the antiviral effect of interferon-alpha, it is possible that glucocorticoid-resistant AIDS patients have greater defences against viral infection than other AIDS patients. As interferon-alpha is melanogenetic, its increased production may also explain the intense skin pigmentation found in patients with the glucocorticoid-resistance syndrome.
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PMID:The syndrome of acquired glucocorticoid resistance in HIV infection. 781 Dec 21

Forty patients (34 males and 6 females) with neurological complaints/manifestations and with a past history of multiple sexual partners attending the Government Rajaji Hospital, Madurai, India between April 1992 and October 1992 were investigated for neurosyphilis. Metabolic disorders, hypertension, ischaemic heart disease, arrhythmias and trauma were excluded. Seven males (17.5%) were found to have neurosyphilis. The youngest was 26 years old and the oldest was 47. All were married and of low socioeconomic background. Meningovascular syphilis was the predominant presentation (6:1). Associated cardiovascular involvement was noticed in one of the cases. There was no associated HIV infection in these cases. The incidence is higher than previous reports from this centre.
Int J STD AIDS
PMID:Prevalence of neurosyphilis at Government Rajaji Hospital, Madurai, India. 794 62


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