Prevalence of antiretroviral resistance in a South London cohort of treatment-naive HIV-1-infected patients.
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Biomedical subjects
Publications and source records attributed to M Zuckerman.
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A number of traditional remedies used in South Africa contain pyrrolizidine alkaloids, some of which are hepatotoxic. We investigated the effect on human HuH-7 cells of Senecio latifolius DC., a plant that is a component of some traditional remedies and which is known to contain toxic pyrrolizidine alkaloids. Cells were also treated with extracts of a standard pyrrolizidine, retrorsine. The changes in the gross morphology of the cells were studied using light microscopy after haematoxylin and eosin staining. The cytoskeleton was investigated using fluorescence-labelled anti-beta-tubulin antibody and the nuclear organisation was studied using fluorescence-labelled antinuclear antibodies. The plant extracts gave rise to dose-dependent gross morphological changes. At high doses, we observed necrosis and at lower doses, destruction of the cytoskeleton, nuclear fragmentation and apoptosis. Doses of less than the equivalent of 330 ng/ml retrorsine led to multinucleated cells with failure in spindle formation and clumping of nuclear chromatin. This latter finding suggests that chronic low-dose treatment with such traditional remedies could give rise to teratogenic and/or carcinogenic effects.
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BACKGROUND: Individuals undergoing therapeutic immunosuppression are at risk of severe varicella-zoster virus (VZV) infection, particularly those without evidence of previous infection. METHODS: Eleven children, median age 10 months (range 5.5 months to 7 years and 9 months) received one dose of varicella vaccine (Varilrix, SmithKline Beecham plc, UK) before liver transplantation (median interval 95 days, range 40-289 days). The serological response to varicella vaccine was evaluated retrospectively and matched with the outcome and management of any subsequent exposures to VZV. RESULTS: Three children responded postimmunization, six children showed no response, and in two children the outcome was difficult to interpret having received blood products. Four children required varicella-zoster immunoglobulin prophylaxis posttransplantation, two of whom developed mild chickenpox. CONCLUSIONS: Only 3 of 11 children developed a clear antibody response to varicella vaccine. Administration of varicella vaccine did not affect the management of subsequent VZV exposures.
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Inaccurate quantification of plasma HIV RNA concentration may be detrimental to patient care, yet little is known about how reproducible results are within and between laboratories. Each week between January and April 1998 a different laboratory represented at the Public Health Laboratory Service HIV Diagnosis Forum sent aliquots of the same anti-HIV positive plasma specimen by First Class Mail to the other 12 laboratories and to itself. Aliquots were frozen on receipt and examined in the next assay run. At the end of the 13 week period each laboratory reported their findings and provided further information about the specimen that they had dispatched. The correlation of results between laboratories and between the four different assay kits used was generally satisfactory. HIV RNA concentrations determined by the Roche Monitor and AcuGen kits were higher, and by the Chiron Quantiplex v 2.0 kit lower, than average. The Chiron Quantiplex gave the most reproducible concentrations. Nine 'below detection limit' results occurred, associated with three specimens. One specimen gave a below detection limit result in every one of six laboratories using the Organon Teknika Nuclisens HIV-1 QT kit, and was found to contain viral RNA of HIV-1 clade G. Another below detection limit result was probably due to technical error, and the remaining two to assay insensitivity. The findings suggested that an unsustained change in HIV RNA of <log(10)1.00 may not be a reliable basis for modifying treatment. This study confirms the need for performance assessment and for conservative interpretation of isolated changes in the estimate of HIV RNA concentration. Parallel testing of consecutive specimens from individual patients, though expensive, probably offers the best indication of significant change in the HIV RNA concentration.
In a study carried out in two hospitals in South Africa the authors identified 20 children suffering from hepatic veno-occlusive disease thought to be caused by the administration of traditional remedies. The predominant clinical presentation was ascites of various degrees and hepatomegaly. There was a high morbidity and mortality in the young infants, and in those cases who survived and were followed up the clinical pattern was one of progression to cirrhosis and portal hypertension. Pyrrolizidine alkaloid poisoning is one of the causes of the veno-occlusive disease. Therefore there is a need for objective confirmation of this. In four of our cases an on-admission urine specimen was available and in all of these a simple colorimetric screening test confirmed the presence of pyrrolizidine alkaloids. The other cases were admitted from peripheral hospitals and clinics and urine was not obtained until after 72 h, a time at which the levels of pyrrolizidines in urine were below the limit of sensitivity of the screening test. The screening method is helpful for the detection of acute ingestion of pyrrolizidines in large amounts, but is not sufficiently sensitive for the detection of chronic ingestion of smaller amounts. Nevertheless, in those patients who have hepatomegaly and ascites a positive finding of pyrrolizidines is important and may remove the necessity for expensive and invasive investigative measures.
The first part of this article describes a study of the relationships between personality and risk-taking in six areas: smoking, drinking, drugs, sex, driving, and gambling. The participants, 260 college students, were given self-report measures of risky behaviors in each of the six areas and the Zuckerman-Kuhlman five-factor personality questionnaire. Generalized risk-taking (across all six areas) was related to scales for impulsive sensation seeking, aggression, and sociability, but not to scales for neuroticism or activity. Gender differences on risk-taking were mediated by differences on impulsive sensation seeking. The second part discusses biological traits associated with both risk-taking and personality, particularly sensation seeking, such as the D4 dopamine receptor gene. the enzyme monoamine oxidase, and augmenting or reducing of the cortical evoked potential. Comparative studies show relationships between biological markers shared with other species and correlated behaviors similar to sensation seeking in humans. A biosocial model of the traits underlying risk-taking is presented.
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Poisoning with impila (Callilepis laureola) is a recurring phenomenon in South Africa. Cases of poisoning with other plants which contain atractyloside also occur in Europe and the Americas. Since poisoning leads to rapid death from renal and/or hepatic failure, it is suspected that many cases are undiagnosed; this is especially so in South Africa, where patients may die without reaching hospital and do not often admit to ingestion of a traditional remedy. We have developed a thin layer chromatographic method for the detection of impila constituents in urine. We describe the clinical symptoms and the application of the screening method to diagnosis in the case of a mother and child, who both showed symptoms of impila poisoning; the mother died but the child survived. This method is rapid and may be used for the definitive diagnosis in cases of poisoning with atractyloside-containing plants.
Self-handicappers erect impediments to performance to protect their self-esteem. The impediments may interfere with the ability to do well and, as such, may result in poor adjustment. Using a longitudinal design, the present studies examined prospective effects of self-handicapping on coping, academic performance, and several adjustment-related variables (e.g., self-esteem). It was found that, compared to low self-handicappers, high self-handicappers reported higher usage of coping strategies implying withdrawal and negative focus. High self-handicappers performed less well academically, an effect that was mediated in part by poor study habits. Finally, high self-handicapping resulted in poorer adjustment over time, and poorer adjustment resulted in higher self-handicapping over time. These relations are consistent with the idea of a vicious cycle in which self-handicapping and poor adjustment reinforce one another.
Toxicity related to traditional medicines is becoming more widely recognized as these remedies become popular in developed countries. Accidental herbal toxicity occurs not only as a result of a lack of pharmaceutic quality control in harvesting and preparation but also because herbal remedies are believed to be harmless. Although there is a huge amount of data available documenting the pharmacologically active ingredients of many plants, it is seldom helpful to the toxicologist in an acute situation. Current analytic methods such as high-performance liquid chromatography, gas chromatography--mass spectrometry, and immunoassays can provide identification of the toxin in those few cases in which the history or symptoms give a clear lead, but broad screening methods remain to be developed. In most cases of plant poisoning, treatment continues to be only of symptoms, with few specific antidotes available. It is important that toxicologists in the West be alert to the possibility of encountering poisoning in patients due to traditional African remedies.
A study of 185 psychiatric patients with anxiety, mood, and schizophrenic disorders and 185 matched nonpatient controls investigated the effectiveness of the affect trait scales of the revised Multiple Affect Adjective Check List (MAACL-R) in differentiating the three disorders. Univariate and multivariate analyses supported the usefulness of the affect in global and specific diagnostic classifications. The strongest discriminant function described a general dysphoria dimension (Depression plus Anxiety minus Positive Affect) which differentiated the anxiety and mood disorder groups from schizophrenic patients and nonpatient controls. A second discriminant function best differentiated the anxiety from mood disorder groups and was defined by relatively higher anxiety and normal sensation seeking scores among anxiety disorders and relatively higher depression and lower sensation seeking among mood disorders. Schizophrenic disorders could not be reliably distinguished from the other groups by negative affect scales, although they scored lower on positive affect than normals. It was concluded that the MAACL-R was valid in making both global and specific diagnostic classifications.
BACKGROUND: Hepatitis B virus infection originating from hepatitis B surface antigen-negative, hepatitis B core antibody (anti-HBc)-positive organ donors has been documented, and anti-HBc-positive donors have been excluded as liver donors. We assessed the prevalence of anti-HBc in UK organ donors and followed up recipients of organs from anti-HBc-positive donors for serological evidence of posttransplantation hepatitis B virus infection. METHODS: Serum samples from 400 hepatitis B surface antigen-negative organ donors were tested for anti-HBc. RESULTS: Only five (1.25%) of 20 sera in which anti-HBc was initially detected were confirmed as anti-HBc positive on further testing. Posttransplantation serum samples from four recipients of confirmed anti-HBc-positive organs showed no evidence of de novo hepatitis B infection. CONCLUSIONS: The poor specificity of some anti-HBc immunoassays was confirmed and suggests that donor exclusion on the basis of a single anti-HBc-positive result may result in the inappropriate loss of organs.
OBJECTIVE: To investigate the relation between increased fetal nuchal translucency thickness at 10-14 weeks of gestation and maternal-fetal infection. DESIGN: Prospective study. SETTING: Harris Birthright Research Centre for Fetal Medicine. POPULATION: Four hundred and twenty-six chromosomally normal pregnancies with increased fetal nuchal translucency thickness at 10-14 weeks of gestation and 63 with 'unexplained' second or third trimester fetal nuchal oedema or hydrops. METHODS: Maternal serum infection screening and investigations for fetal infection in those with evidence of recent maternal infection. MAIN OUTCOME MEASURES: Maternal and fetal infection. RESULTS: Evidence of recent maternal infection was present in six of the 426 pregnancies (1.4%) with increased fetal nuchal translucency thickness at 10-14 weeks, but in all cases a healthy infant was born with no evidence of infection. In contrast, 'unexplained' second or third-trimester fetal hydrops was associated with maternal infection in six of the pregnancies (9.5%) and in all cases there was evidence of fetal infection. CONCLUSIONS: Maternal-fetal infection is one of the causes of second or third trimester nuchal oedema or fetal hydrops. In contrast, the presence of increased nuchal translucency in the first trimester is not a marker of either maternal or fetal infection.
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C.R. Colvin, J. Block, and D.C. Funder (1995) calculated a self-enhancement index-the discrepancy between favorability of participants' self-ratings and favorability of others' ratings of the participants. They found that the index was negatively correlated with psychological adjustment. However, the discrepancy between self- and other-ratings cannot add to the variance accounted for once self-ratings and other-ratings are controlled for. Consequently, the index cannot properly be used to examine how self-enhancement influences adjustment. An appropriate test for the self-enhancement effect is the interaction between favorability of self- and other-ratings.