Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Retinitis por Citomegalovirus/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Adulto , Recuento de Linfocito CD4 , Retinitis por Citomegalovirus/complicaciones , Retinitis por Citomegalovirus/epidemiología , Retinitis por Citomegalovirus/inmunología , Femenino , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana EdadRESUMEN
SAR studies directed towards the optimization of 2-azetidinone cholesterol absorption inhibitors led to the discovery of 11a, the most potent cholesterol absorption inhibitor yet identified.
Asunto(s)
Anticolesterolemiantes/química , Anticolesterolemiantes/farmacología , Azetidinas/farmacología , Colesterol/metabolismo , Animales , Azetidinas/química , Colesterol/sangre , Cricetinae , Hígado/efectos de los fármacos , Hígado/metabolismo , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Relación Estructura-ActividadRESUMEN
The asymmetric synthesis of a glucuronide conjugate of the 2-azetidinone cholesterol absorption inhibitor Sch 48461 was accomplished to confirm the structure of a metabolite isolated from in vivo sources. Key features of this article include the asymmetric synthesis of 2-azetidinones by Evan's chiral oxazolidinone methodology and glucuronide formation by a Mitsunobu protocol.
Asunto(s)
Anticolesterolemiantes/farmacología , Azetidinas/farmacología , Carbohidratos/química , Animales , Anticolesterolemiantes/química , Azetidinas/química , Cricetinae , Estructura MolecularRESUMEN
Metabolism initiated SAR studies led to the discovery of a new class of potent 2-azetidinone cholesterol absorption inhibitors. These studies found that a heteroatom at the para position of the C-4 phenyl ring is not a requirement for cholesterol absorption inhibition as was suggested by earlier findings. Substitution of Ph-linker-COOR for PhOMe at the C-4 position enhanced cholesterol absorption inhibition.
Asunto(s)
Anticolesterolemiantes/química , Anticolesterolemiantes/farmacología , Azetidinas/química , Azetidinas/farmacología , Colesterol/metabolismo , Animales , Colesterol/sangre , Cricetinae , Hígado/efectos de los fármacos , Hígado/metabolismo , Relación Estructura-ActividadRESUMEN
A series of azetidinone cholesterol absorption inhibitors related to SCH 48461 ((-)-6) has been prepared, and compounds were evaluated for their ability to inhibit hepatic cholesteryl ester formation in a cholesterol-fed hamster model. Although originally designed as acyl CoA: cholesterol acyltransferase (ACAT) inhibitors, comparison of in vivo potency with in vitro activity in a microsomal ACAT assay indicates no correlation between activity in these two models. The molecular mechanism by which these compounds inhibit cholesterol absorption is unknown. Despite this limitation, examination of the in vivo activity of a range of compounds has revealed clear structure-activity relationships consistent with a well-defined molecular target. The details of these structure-activity relationships and their implications on the nature of the putative pharmacophore are discussed.
Asunto(s)
Anticolesterolemiantes/química , Colesterol/metabolismo , Absorción , Animales , Azetidinas/química , Ésteres del Colesterol/biosíntesis , Cricetinae , Enlace de Hidrógeno , Hígado/metabolismo , Masculino , Mesocricetus , Microsomas Hepáticos/enzimología , Conformación Molecular , Estructura Molecular , Ratas , Esterol O-Aciltransferasa/antagonistas & inhibidores , Relación Estructura-ActividadRESUMEN
Conformational restriction of previously disclosed acyclic (diphenylethyl)diphenylacetamides led to the discovery of several potent inhibitors of acyl CoA:cholesterol acyltransferase (ACAT). cis-[2-(4-Hydroxyphenyl)-1-indanyl]diphenylacetamide (4a) was the most potent ACAT inhibitor identified (IC50 = 0.04 microM in an in vitro rat hepatic microsomal ACAT assay, ED50 = 0.72 mg/kg/day in cholesterol-fed hamster.
Asunto(s)
Inhibidores Enzimáticos/síntesis química , Esterol O-Aciltransferasa/antagonistas & inhibidores , Animales , Cricetinae , Inhibidores Enzimáticos/farmacología , Microsomas Hepáticos/enzimología , Ratas , Relación Estructura-ActividadRESUMEN
Following blunt abdominal trauma, patients still may be actively bleed ing, despite seeming hemodynamically stable. By detecting extravasation of contrast-enhanced blood in the absence of any other evidence to support solid visceral injury as the source, computed tomography (CT) scanning was able to indicate ongoing hemorrhage in two patients, thought most likely of mesenteric origin. This information influenced the decision for intervention, which in these two cases was laparotomy, where bleeding torn mesenteric vessels were confirmed.
Asunto(s)
Traumatismos Abdominales/complicaciones , Hemoperitoneo/diagnóstico por imagen , Mesenterio/lesiones , Tomografía Computarizada por Rayos X , Heridas no Penetrantes/complicaciones , Adulto , Femenino , Hemoperitoneo/etiología , Hemoperitoneo/cirugía , Humanos , MasculinoRESUMEN
Two aspects of the role of women in the AIDS epidemic are discussed. Firstly, the role of women in the epidemic and secondly how does HIV/AIDS affect women. Currently it is estimated that over four million women are infected with HIV and more attention is increasingly being paid to this group. Women have been functionally socialized in a dual role, namely that of care giver and service provider. The generally low status of women in the developing world needs to be corrected by empowering women to deal with the epidemic through education and equal social and sexual status to men. Epidemiological data concerning women and HIV/AIDS are presented and the possible effect of HIV/AIDS on women is discussed. Candidiasis, pelvic inflammatory diseases and cervical neoplastic lesions require further attention. Finally, a number of recommendations, including human rights, are presented to enable women worldwide successfully to cope with the HIV epidemic.
PIP: International and South African data indicate that increasing numbers of women are becoming infected with the HIV and developing AIDS worldwide. It is estimated that over 4 million women are currently infected with the HIV virus. HIV/AIDS is known to affect women in several ways: 1) women of reproductive age are the fastest growing segment of the population to be infected; 2) both estrogen and progesterone affect the immune system and therefore may influence the natural history of HIV infection; 3) the rate of CD4 cell loss is faster in HIV-positive than in HIV-negative pregnant women and infected homosexual men. HIV appears to affect profoundly the frequency of development, the degree of severity, and the rate of progression of cervical neoplastic lesions. Candidiasis, pelvic inflammatory diseases, and cervical neoplastic lesions and their possible effects on HIV/AIDS in women require further attention. In order to enable women worldwide to successfully cope with the HIV/AIDS epidemic, the author recommends: 1) universal human rights for all women must be accepted and reinforced; 2) female-controlled methods to protect against HIV transmission to women should be developed; 3) community empowerment of women to deal with the HIV/AIDS problem must be implemented; and 4) long-term studies in women must be implemented to determine the natural history and course of HIV infection and the efficacy of drugs. Because of the possibility of termination of pregnancy and early recognition of pediatric HIV infection, antenatal HIV testing of all women, with consent, should be seriously considered. South African women must mobilize themselves, their resources and talents, and rise in solidarity and declare war against AIDS.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/prevención & control , Países en Desarrollo , Identidad de Género , Salud de la Mujer , Derechos de la Mujer , Adaptación Psicológica , Cuidadores , Escolaridad , Femenino , Humanos , Poder Psicológico , Factores SexualesRESUMEN
Even in the definitive textbook on vulvar conditions edited by Ridley no description of neuroma of the vulva exists, although neural tumors and neurofibroma are considered. The medical literature covering the past 25 years records only one case of terminal fiber neuroma in an episiotomy scar and one neuroma of the clitoris. The latter occurred in a patient with neurofibromatosis. This report documents a symptomatic neuroma of the labia minora considered to be the result of a vulval injury. It is postulated that dyspareunia related to episiotomy may be associated with disorganized proliferation of proximal nerve stumps. Because of the rarity and lack of expertise on management of vulval neuroma, we suggest that the International Society for the Study of Vulvar Disease (ISSVD) further investigate this condition.
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Neuroma , Neoplasias de la Vulva , Adulto , Femenino , Estudios de Seguimiento , Humanos , Neuroma/diagnóstico , Neuroma/etiología , Neuroma/patología , Neuroma/cirugía , Vulva/lesiones , Neoplasias de la Vulva/diagnóstico , Neoplasias de la Vulva/etiología , Neoplasias de la Vulva/patología , Neoplasias de la Vulva/cirugíaRESUMEN
The prevalence of anti-HCV was studied in a cohort of 2,072 South Africans. The results were compared in selected recently collected sera and in stored sera. The serum ALT and anti-HBc were also studied as surrogate markers in this population. The following groups were tested: (a) 498 urban, black blood donors (b) 500 white blood donors (c) 500 Asian blood donors (d) 216 rural hospitalized patients (e) 358 rural mineworkers. Sera found positive by the original ELISA were retested, and reproducibly positive tests in rural black men (group d) were confirmed both by recombinant immunoblot assay and by a second ELISA. An anti-HCV prevalence of 1.2%, 0.8%, and 0.6% in urban blacks, Asians, and whites was found. Antibodies to hepatitis B core antigen were found in 42.9%, 3.4%, and 1.2% of black, Asian, and white donors, respectively; 76% of donors positive for anti-HCV were anti-HBc negative. In rural African men, 17% of stored serum samples and 9.2% of recently collected serum samples were positive for anti-HCV. In this cohort 3.84% were positive by all three assays. These results suggest that the prevalence of anti-HCV in low and high-risk South African urban blood donors is comparable to high and low prevalence areas in Europe, the United States, and Japan, but indicates a relatively high degree of exposure to hepatitis C in rural African men. The reactivity of stored, frozen sera in this population requires further investigation. In South African urban blood donors, surrogate marker testing will not expedite HCV screening.
Asunto(s)
Alanina Transaminasa/sangre , Anticuerpos Antihepatitis/análisis , Antígenos del Núcleo de la Hepatitis B/inmunología , Hepatitis C/epidemiología , Hepatitis C/inmunología , Adulto , Donantes de Sangre , Estudios de Cohortes , Etnicidad , Humanos , Masculino , Sudáfrica/epidemiología , Población Urbana , Población BlancaRESUMEN
Tests were carried out on 198 patients with inherited coagulation disorders attending haemophilia clinics of Johannesburg and Baragwanath Hospitals for the prevalence of antibodies to the human immunodeficiency virus (HIV). This cohort of patients has been treated with locally produced (South African) blood products from volunteer donors, except for a 15-month period in 1982-1984 when, owing to a shortage of locally produced material, an imported large donor-pool US factor VIII concentrate was used. Not all patients received this material. Of the haemophilia A patients who received the imported factor VIII concentrate, 85% were seropositive, while only 3% of the patients who received locally produced small donor-pool products were seropositive. No factor VIII-deficient patients have seroconverted while using small donor-pool products, since the introduction of routine screening of blood donations and strict exclusion criteria of donors. However, despite testing of blood products, 3 patients receiving locally produced factor IX concentrate (4,000 donors) seroconverted in 1988, having previously been HIV-negative. Factors influencing the choice of blood products to be used, especially in South Africa, are discussed.
Asunto(s)
Seropositividad para VIH/epidemiología , Hemofilia A/terapia , Reacción a la Transfusión , Adolescente , Adulto , Anciano , Trastornos de la Coagulación Sanguínea/terapia , Niño , Preescolar , Factor IX/administración & dosificación , Factor VIII/administración & dosificación , Humanos , Lactante , Persona de Mediana Edad , Prevalencia , Protrombina/administración & dosificación , Sudáfrica/epidemiologíaRESUMEN
Infections can cause autoantibody production. The purpose of this study was to determine the prevalence of autoantibodies in patients with chronic mycobacterial infections. Sera from 41 leprosy patients and from 49 untreated and 73 treated tuberculosis (TB) patients were tested for the presence of rheumatoid factor, antinuclear factor, and several other autoantibodies. The rheumatoid factor, measured by the Rheuma Tec RF latex test, was positive in 2.4% of the leprosy patients and 2.7% of the treated TB patients but absent in the untreated TB group. The titers ranged from 40 to 160 international units. Positivity was dependent upon the technique utilized, and existed in 21% of untreated TB group and 4% of the treated TB patients when using the Rheuma-Wellcotest technique. The antinuclear antibody was positive in 7.3% of the leprosy group, 6.1% of the untreated TB group, and 15% of the treated TB patients (p = 0.0125). Antinuclear antibody positivity correlated with the duration of treatment of the TB patients (p = 0.025). The antinuclear antibody titers were low and gave no specific pattern on staining. No patient had antibodies against native deoxyribonucleic acid, ribonuclear protein, Ro (SS-A) or La (SS-B) antigens. Due to their low prevalence and frequency in these chronic infections, these autoantibodies should not lead to confusion in distinguishing these conditions from the connective tissue diseases.
Asunto(s)
Anticuerpos Antinucleares/sangre , Lepra/inmunología , Factor Reumatoide/sangre , Tuberculosis Pulmonar/inmunología , Adulto , Población Negra , Femenino , Humanos , Lepra/epidemiología , Lepra/etnología , Masculino , Persona de Mediana Edad , Prevalencia , Sudáfrica/epidemiología , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/etnologíaRESUMEN
A survey conducted in rural southern African black subjects indicated that dietary iron overload remains a major health problem. A full blood count, erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding capacity, ferritin, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and serological screening for hepatitis B and human immunodeficiency virus (HIV) infections were carried out in 370 subjects (214 inpatients and 156 ambulatory Mozambican refugees). The fact that the geometric mean (SD range) serum ferritin concentration was much higher in the male hospital patients than in subjects living in the community [1,581 micrograms/l (421-5,944 micrograms/l) and 448 micrograms/l (103-1,945 micrograms/l) respectively] suggested that dietary iron overload was not the only factor raising the serum ferritin concentration. The major additional factor appeared to be inflammation, since the geometric mean (SD range) serum CRP was significantly higher in male hospital patients [21 mg/l (8-53 mg/l)] than in subjects in the community [3 mg/l (1-5 mg)]. Alcohol ingestion, as judged by history and by serum GGT concentrations, was also associated with significantly raised serum ferritin concentrations. This finding was ascribed to the fact that traditional brews are not only associated with alcohol-induced hepatic damage but are also a very rich source of highly bio-available iron. The role of iron overload in the genesis of the raised serum ferritin concentrations are confirmed in the diagnostic liver biopsy study. The majority of biopsies showed heavy siderosis, with varying degrees of hepatic damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Negro o Afroamericano , Hierro/envenenamiento , Adolescente , Adulto , Anciano , Consumo de Bebidas Alcohólicas , Población Negra , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Dieta , Femenino , Ferritinas/sangre , Humanos , Masculino , Persona de Mediana Edad , Población Rural , Sudáfrica , gamma-Glutamiltransferasa/sangreRESUMEN
A review of human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) in South Africa between 1982 -1988 is presented. One hundred and sixty-six cases of AIDS have been seen in South Africa so far, with a mortality rate of 59.2%. There has been a predicted and alarming increase in the number of cases of AIDS in the black population. A total of 1857 HIV antibody-positive sera have been tested by various laboratories in the RSA, but this figure excludes sera found to be positive in the mining industry. The HIV-positive and AIDS cases include members of all population groups. A number of surveillance studies are presented. These revealed that beyond the groups at high risk for HIV infection the prevalence of this infection is still very low. Of an estimated 710,000 blood donors tested, 244 were positive for HIV-1 antibodies. Although 1 case of HIV-2 infection was detected in South Africa, this does not constitute a problem at present. No evidence of infection with HIV-1 was detected in southern and central African sera taken between 1970 and 1974. In the absence of a vaccine and specific treatment a change of sexual behavior to one of safer sex practices through education is the only means we have of containing the spread of the epidemic.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/epidemiología , Seropositividad para VIH/epidemiología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Negro o Afroamericano , Bisexualidad , Población Negra , Atención Odontológica , Femenino , Hemofilia A/complicaciones , Homosexualidad , Humanos , Masculino , Embarazo , Sarcoma de Kaposi/complicaciones , Sudáfrica/epidemiología , Trastornos Relacionados con Sustancias/complicaciones , Población BlancaRESUMEN
Acquired immunodeficiency syndrome (AIDS) is considered to be the major health threat of the 20th century. The only way to contain the spread of AIDS is by prevention of infection in the first place. This task is essentially one of education. Because the South African Institute for Medical Research is traditionally associated with the prevention of infectious diseases, an AIDS Centre was established to promote education. As part of the launching of the Centre in January 1988, a series of four 1-day courses was held for different target groups. Attendance rates were high and all participants completed a pre- and post-test questionnaire designed to evaluate the effectiveness of the courses and identify existing level of knowledge, present needs and possible future demands. Collected data were examined by correlation analysis, the chi-square test and the t-test. Results generally showed improved changes in knowledge and attitudes about AIDS, and pointed the way forward for future education interventions in the community.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/prevención & control , Educación Continua , Educación en Salud/métodos , Técnicos Medios en Salud/educación , Educación Médica Continua/métodos , Estudios de Evaluación como Asunto , Centros de Información , Psicología/educación , Servicio Social/educación , Sudáfrica , Encuestas y CuestionariosRESUMEN
Ninety-two patients with SLE, 36 black and 56 white, were studied prospectively for photosensitivity and anti-Ro (SS-A) and anti-La (SS-B) antibodies. Photosensitivity was found in 19% of black patients, compared to 71% of white patients (p = 0.001). Anti-Ro antibodies were found in 69% of black and 54% of white patients (p = 0.013). Photosensitivity was present in 87% of Ro-positive white patients and in 54% of Ro-negative white patients (p = 0.007). However, in black patients with SLE there was a strong negative association: 4% of Ro-positive patients were photosensitive while 55% of Ro-negatives were photosensitive (p = 0.001). This suggests that black SLE patients may possess a factor which 'blocks' photosensitivity, perhaps by preventing local tissue damage caused by the interaction of Ro antibodies and ultraviolet light.
Asunto(s)
Anticuerpos Antinucleares/análisis , Lupus Eritematoso Sistémico/inmunología , Trastornos por Fotosensibilidad/etiología , Población Negra , Humanos , Lupus Eritematoso Sistémico/complicaciones , Población BlancaRESUMEN
Chronic hepatitis B infection is an important cause of cirrhosis and subsequent hepatocellular carcinoma in South Africa. The disease can now be prevented by vaccination, but second-generation genetically engineered vaccines still necessitate planned allotment. We have tested 29,312 black southern African mineworkers for hepatitis B surface antigen (HBsAg) to indirectly ascertain the relative prevalence of hepatitis B infection in diverse linguistic and ethnic groups. The overall prevalence of HBsAg in this cohort of predominantly rural men was 9.9%, but the prevalence in men from different regions varied from 5.5% to 14%. The relative prevalence in 200 magisterial districts was ranked; these percentage prevalences ranged from 0% to 17%. A significantly lower mean prevalence was detected in Southern Sotho subjects than in those from coastal districts (Nguni). Based on these data, we believe that there are perhaps 2 million hepatitis B carriers in South Africa. The collected data in this report could provide a basis for a broad-based vaccine campaign whereby hepatitis B vaccine could be targeted to high-priority districts initially. This strategy could rapidly reduce the critical mass of carriers, and hasten control of the disease.
Asunto(s)
Hepatitis B/epidemiología , Hepatitis Crónica/epidemiología , Vacunas contra Hepatitis Viral , Adolescente , Adulto , África Austral , Negro o Afroamericano , Anciano , Población Negra , Hepatitis B/prevención & control , Vacunas contra Hepatitis B , Hepatitis Crónica/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Minería , VacunaciónRESUMEN
Although hepatitis B infection is endemic in southern Africa, a changing epidemiology of the disease has recently been documented in the region. The authors surveyed migrant southern African male mineworkers during 1986 to establish the prevalence of chronic hepatitis B and D (delta) infection in their areas of origin. Hepatitis B surface antigen (HBsAg) was tested in 29,312 adult male mineworkers from 18 geographic regions, encompassing the diverse tribal and linguistic groups in the region, as well as in expatriate mineworkers from neighboring southern African countries. The same cohort was also tested for antibody to human immunodeficiency virus (HIV). Selected hepatitis B carriers were also tested for hepatitis B virus deoxyribonucleic acid (DNA), antibody to hepatitis D (anti-HD), and alpha-fetoprotein. The overall prevalence of HBsAg in this survey was 9.9%. However, the prevalence varied from 5.5% to 14% in different ethnic groups. A minority of carriers (4.9%) had replicative hepatitis B infection and were hepatitis B virus DNA-positive. Only 0.6% of tested carriers were anti-HD-positive. Alpha-fetoprotein determinations were abnormal in 1.2% of hepatitis B-positive men. These data show that although chronic hepatitis B infection remains widespread in southern Africa, carrier rates vary significantly from region to region. In contrast, hepatitis D co-infection remains extremely uncommon. These baseline seroprevalence data also establish that HIV infection was, in 1986, a rare infection in the indigenous population of South Africa.