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Biomedical subjects

D Wilkinson

Publications and source records attributed to D Wilkinson.

At least 181 records · Page 10Linked to original sources
PubMed1997

Cerebral noradrenaline spillover and its relation to muscle sympathetic nervous activity in healthy human subjects.

Studies using internal jugular vein blood sampling in human subjects have demonstrated the release of noradrenaline from the brain and have provided a link between central nervous system noradrenergic neuronal activity and renal, cardiac and total body sympathetic activity. The aim of this study was to further categorise the dependence of regional sympathetic nervous function on central nervous system noradrenergic neuronal processes by combining measures of internal jugular venous noradrenaline spillover, as an indicator of brain noradrenaline release, and cerebral blood flow scans with measures of the overall integrated neuronal firing rate for the body as a whole, the spillover of noradrenaline into the coronary sinus and with measurements of resting muscle sympathetic nerve activity. Positive veno-arterial plasma noradrenaline gradients were found across the brain, with the plasma concentration being 17 +/- 3% (p < 0.01) greater in the internal jugular vein. Linear regression analysis revealed a significant relationship between the degree of muscle sympathetic nerve activity and the spillover of noradrenaline from subcortical brain regions (y = 0.1 x + 16.0; r = 0.81, p < 0.02). The rate of spillover of noradrenaline for the body as a whole also bore a significant association with the rate of subcortical noradrenaline spillover (y = 0.01x + 2.33; r = 0.71, p < 0.05). Cortical noradrenaline spillover was not related to any of the sympathetic nervous system parameters measured in this study. The demonstration of a direct relationship between the rate of peroneal nerve firing and the spillover of noradrenaline from subcortical brain regions provides further support for the concept of central nervous system noradrenergic cell groups behaving in a sympathoexcitatory role.

Adult↗
PubMed1997

Cochliobolic acid, a novel metabolite produced by Cochliobolus lunatus, inhibits binding of TGF-alpha to the EGF receptor in a SPA assay.

Cochliobolic acid (1), a novel biologically active natural product, is produced by submerged fermentation of Cochliobolus lunatus. Compound 1 was determined to be a novel polyketide possessing a substituted tetrahydrofuran ring, a conjugated polyene chain and a 1,2-diketone moiety, by interpretation of NMR, MS, and UV/vis spectroscopic data. Compound 1 inhibits the binding of TGF-alpha to the EGF receptor of the human epidermal cell line A431 in a SPA assay with an IC50 of 1.6 microM.

Chemical Phenomena↗
PubMed1997

Epidemiology of syphilis in pregnancy in rural South Africa: opportunities for control.

The paper describes the epidemiology, risk factors and impact on pregnancy outcome of syphilis in pregnant women in rural South Africa. Prevalence was determined from laboratory records. A case-control study of 200 women (50 cases with syphilis) was done to investigate possible risk factors. To determine the impact on pregnancy outcome, and to evaluate the effect of treatment, a retrospective cohort was constructed. Overall prevalence of syphilis was 6.5%; it was highest in the urban antenatal clinic (9%). The odds ratios for syphilis in women gravidity 3-5 compared to gravidity 6 was 3.2 and 2.3 compared to women with gravidity 2 or less. For women with a previous birth, those with a previous perinatal death were 3.2 times more likely to have syphilis after adjusting for other risk factors. Pregnancy outcome was available for 187 women. The adjusted odds ratio of an adverse pregnancy outcome in women with syphilis was 11.8. All still births occurred in women with syphilis. The prevalence of syphilis is high in this rural area and screening should be applied to all women. Although screening was comprehensive, less than half of the detected cases were fully treated and a poor perinatal outcome ensued. On-site testing for syphilis at the time of booking would allow treatment to start immediately.

Adolescent↗
PubMed1997

Coping with Africa's increasing tuberculosis burden: are community supervisors an essential component of the DOT strategy? Directly observed therapy.

Tuberculosis incidence in Africa is increasing dramatically and fragile health systems are struggling to cope. Potential coping capacity may lie within affected communities but this capacity needs to be harnessed if tuberculosis is to be controlled. Since 1991 all patients with tuberculosis in Hlabisa health district, South Africa have been eligible for community-based directly observed therapy (DOT). Patients are supervised either by a health worker (HW) in a village clinic, or in the community by a community health worker (CHW) or a volunteer lay person (VLP). Tuberculosis incidence increased from 312 cases in 1991 to 1250 cases in 1996. By December 1995, 2622 (87%) of 3006 patients had received DOT, supervised mainly by VLP (56%) but also by HW (28%) and CHW (16%). The proportion supervised by HW fell from 46% in 1991 to 26% in 1995 (P < 0.0001). More patients supervised by VLP (85%) and CHW (88%) than by HW (79%, P = 0.0008) completed treatment. Case-holding by HW declined more between 1991 and 1995 (84% to 71%, P = 0.02) than did case-holding by both CHW (95% to 90%. P = 0.7) and VLP (88% to 84%, P = 0.4). Mortality was similar (4-6%) and stable over time, irrespective of the supervisor. High tuberculosis treatment completion rates are achievable and sustainable for several years in resource-poor settings despite a massively increased case load if community resources are harnessed. Patients may be more effectively supervised by voluntary lay people than by health workers under these circumstances, without being placed at increased risk. These findings suggest that community supervisors may be an essential component of any DOT strategy.

Antitubercular Agents↗
PubMed1997

Molecular epidemiology and transmission dynamics of Mycobacterium tuberculosis in rural Africa.

The relative contribution of reactivated and recently acquired tuberculosis to the disease burden in developing countries is unknown, as are the settings within which most transmission occurs. In an attempt to answer these questions, we combined molecular techniques (restriction fragment length polymorphism analysis) and conventional epidemiology (risk factor analysis and contact tracing) to study 246 consecutive cases of smear-positive tuberculosis in rural South Africa. We estimate that 29-43% of the cases were recently acquired, as they were clustered. We were unable to identify firm transmission links between 73% of clustered cases. Our findings suggest that most smear-positive tuberculosis in rural Africa is both recently acquired and casually transmitted. Tuberculosis control may depend more on promoting early presentation, rapid diagnosis and vaccine development than on chemotherapy.

Adult↗
PubMed1997

Reducing perinatal mortality in developing countries.

The perinatal mortality rate (PNMR) is a key health status indicator. It is multifactorial in aetiology and is significantly influenced by the quality of health care. While there is an ethical imperative to act to improve quality of care when deficiencies are apparent, the lack of controls--when an interventions is applied to an entire service--makes it difficult to infer a causal relationship between the intervention and any subsequent change in PNMR. However, by specifically measuring avoidable perinatal deaths (those due to error or omission on the part of the health service), this limitation is partially overcome, and the impact of the intervention can be more rigorously evaluated. This paper reports the impact of perinatal audit in a rural African health district between 1991 and 1995. A total of 21,112 consecutive births were studied: the average number of deliveries increased by 31% from 325 to 424 per month. The PNMR (birth weight > or = 1000g) in 1991 was 27/1000, increased to 42/1000 in 1992, and fell steadily to 26/1000 in 1995 (40% reduction; p = 0.002). The proportion of avoidable deaths fell from 19% in 1991 to zero in the second half of 1995 (p = 0.0008). While factors associated with perinatal mortality are many, complex, and interrelated, this report suggests that mortality can be reduced significantly in resource-poor settings by improving quality of health care. Including the measurement of avoidable deaths in perinatal audit allows the impact of interventions to be more rigorously assessed than by simple measuring the PNMR.

Africa↗
PubMed1997

On-site HIV testing in resource-poor settings: is one rapid test enough?

OBJECTIVE: To determine the feasibility, accuracy and cost-effectiveness of a rapid, on-site, HIV testing strategy in a rural hospital, and to assess its impact on test turnaround time and the proportion of patients post-test counselled. DESIGN: Prospective comparison of two testing strategies [double rapid test on-site versus central enzyme-linked immunosorbent assay (ELISA)-based testing], and an economic evaluation. SETTING: Hlabisa Hospital, a rural South African district hospital. PATIENTS: A total of 454 consecutive adult inpatients requiring and consenting to HIV testing as part of their clinical management. MAIN OUTCOME MEASURES: Concordance between rapid tests, and between the rapid and ELISA strategies, test turnaround time, proportion of patients post-test counselled, and cost-effectiveness. RESULTS: HIV seroprevalence was 49.6%. Both rapid tests were concordant in all patients [one-sided 95% confidence interval (CI) of probability, 99.3-100]. The rapid strategy was 100% sensitive (95% CI, 97.9-100) and 99.6% specific (95% CI, 97.2-100) compared with the ELISA strategy. The mean interval between ordering a test and post-test counselling fell from 21 days prior to the introduction of the rapid test strategy to 4.6 days after its introduction (P < 0.00001). The proportion of patients post-test counselled increased to 96% from 17% after the introduction of the rapid test strategy (P < 0.00001). By using a double rapid test strategy the cost per patient post-test counselled was almost halved to US$ 11. Accuracy of the rapid strategy was not substantially increased by performing two tests. CONCLUSION: In high prevalence, resource-poor settings, rapid, on-site HIV testing is feasible, accurate and highly cost-effective, substantially increasing the number of patients post-test counselled. A single rapid test may be sufficient.

AIDS Serodiagnosis↗
PubMed1997

Tampon sampling for diagnosis of bacterial vaginosis: a potentially useful way to detect genital infections?

Genital tract infections are important causes of ill health in developing countries, but diagnosis is difficult. Bacterial vaginosis (BV) was correctly diagnosed by using a vaginal specimen obtained by tampon sampling in 22 of 24 women (91.6%) for whom BV was diagnosed by Gram staining. The yield for other vaginal infections was higher (28% for Trichomonas vaginalis and 32.7% for Candida albicans) than it was for cervical infections (0% for Neisseria gonorrhoeae and 30% for Chlamydia trachomatis). Tampon sampling was acceptable to patients and may facilitate diagnosis of genital infections in developing countries.

Bacterial Infections↗
PubMed1997

Promiscuous use of CC and CXC chemokine receptors in cell-to-cell fusion mediated by a human immunodeficiency virus type 2 envelope protein.

The CC chemokine receptors CCR5, CCR2, and CCR3 and the CXC chemokine receptor CXCR4 have been implicated as CD4-associated cofactors in the entry of primary and cell line-adapted human immunodeficiency virus type 1 (HIV-1) strains. CXCR4 is also a receptor for T-cell-line-adapted, CD4-independent strains of HIV-2. With the exception of this latter example, little has been reported on the entry cofactors used by HIV-2 strains. Here we show that a CD4-dependent, T-cell-line-adapted HIV-2 strain uses CXCR4 and, to a lesser extent, CCR3 for fusion with and infectious entry into cells. In a cell-to-cell fusion assay, the envelope protein of this virus can utilize a wider repertoire of chemokine receptors to induce fusion. These include CCR1, CCR2, CCR3, CCR4, CCR5, CXCR2, and CXCR4. Kinetic analysis indicated that cell lines expressing the receptors that support infection, CXCR4 and CCR3, form syncytia more rapidly than do cell lines expressing the other receptors. Nevertheless, although less efficient, fusion with CXCR2 expressing cells was specific, since it was inhibited by antibodies against CXCR2. The extensive use of chemokine receptors in cell-to-cell fusion has implications for understanding the molecular basis of CD4-chemokine receptor-induced lentivirus fusion and may have relevance for syncytium formation and the direct cell-to-cell transfer of virus in vivo.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Inhibition of human immunodeficiency virus fusion by a monoclonal antibody to a coreceptor (CXCR4) is both cell type and virus strain dependent.

CXCR4 (also termed fusin, LESTR, or HUMSTR) is a member of the G-protein-coupled chemokine receptor family with seven membrane-spanning domains. CXCR4 acts as a coreceptor for syncytium-inducing human immunodeficiency virus type 1 (HIV-1) strains, conferring entry into CD4+ cells. We show here that a novel mouse monoclonal antibody (12G5) that recognizes CXCR4 blocked cell-to-cell fusion and cell free-virus infection of CXCR4+ CD4+ RD rhabdomyosarcoma cells by seven HIV-1 and HIV-2 strains that had various cell tropisms for different CD4+ human cell types. Yet the majority of the members of the same virus panel resisted 12G5 inhibition on T-cell lines. When inhibition was observed on these cell types, it was both cell type and virus strain dependent. In at least one situation, 12G5 failed to block LAI infection of cells expressing CXCR4 as the only available coreceptor. Our observations suggest that CXCR4 could be processed or presented differently depending on the cell type, allowing some strains to evade 12G5 inhibition. Alternatively, since several of the viruses could infect certain CXCR4- CD4+ cell lines, it is conceivable that alternative coreceptors are active, enabling individual HIV strains to choose between compatible coreceptors during entry into cells. Moreover, the strain dependency of 12G5 inhibition implies that the interaction of different HIVs with CXCR4 varies.

Animals↗
PubMed1997

CD4-independent infection by human immunodeficiency virus type 2 strain ROD/B: the role of the N-terminal domain of CXCR-4 in fusion and entry.

The human immunodeficiency virus type 2 (HIV-2) strain ROD/B can efficiently use the 7tm chemokine receptor CXCR-4 as a primary receptor to enter CD4-negative cells. We have stably expressed CXCR-4 on mink lung Mv-1-lu and feline kidney CCC cells (normally restrictive to HIV entry) and have shown efficient fusion, entry, and replication of ROD/B. Mutation of the two N-linked glycosylation sites on CXCR-4 (N11-->I, and N176-->Q) or pretreatment of CCC or Mv-1-lu cells expressing wild-type CXCR-4 with the glycosylation inhibitor tunicamycin increased fusion and entry by ROD/B. Deletion of portions of the N terminus of CXCR-4 resulted in a 3- to 10-fold decrease in cell-free infection by ROD/B and complete inhibition of cell-cell fusion by both ROD/B and another HIV-2 strain, CBL23. These data suggest that the N-terminal domain of CXCR-4 is involved in but is not essential for the efficient fusion of ROD/B with CD4-negative cells. Deletion of the C-terminal (intracellular) domain of CXCR-4 did not significantly affect entry by ROD/B, indicating that intracellular signalling through this domain does not play a significant role in entry by HIV-2.

Amino Acid Sequence↗
PubMed1997

Family planning services in developing countries: an opportunity to treat asymptomatic and unrecognised genital tract infections?

OBJECTIVE: To determine the prevalence of asymptomatic and unrecognised genital tract infections among women attending a family planning clinic in rural South Africa. METHODS: 189 consecutive women had genital samples taken to diagnose infection with Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Candida albicans, Treponema pallidum, and HIV, and to diagnose bacterial vaginosis. RESULTS: Mean age was 25 years; 155 (82%) were unmarried, 156 (83%) were currently using contraception, and 41 (22%) reported having an STD treated in the preceding 12 months. Although none volunteered abnormal urogenital symptoms, 74 (39%) had at least one elicited by direct questioning. 119 women (63%) had at least one genital infection: N gonorrhoeae (eight; 4%), C trachomatis (14; 8%), T vaginalis (26; 14%), C albicans (56; 30%), active syphilis (15; 8%), HIV (44; 24%), and bacterial vaginosis (29; 15%). 49 women (26%) had multiple infections. Most infections (71; 60%) were asymptomatic. Symptomatic women failed to recognise and report their symptoms, and routine services failed to detect the infections. CONCLUSION: Prevalence of genital tract infection is high among these women, most infections are asymptomatic, and symptomatic infections are frequently not recognised. Women attending family planning clinics in such settings should be screened for syphilis and offered testing for HIV infection. Strategies to detect and treat other genital infections need to be developed.

Adult↗
PubMed1997

Histopathology services in a rural African hospital: how audit can improve service.

Audit is about doing things right. We undertook a detailed audit of the histopathological service at a rural district hospital in Africa because delays in obtaining biopsy results had been noted by clinicians. A wide range of serious pathology was found in the 100 consecutive biopsies reviewed. It took 26 days on average from the time a biopsy was taken to the time the result was returned to the clinician, and most of this delay was administrative in nature, occurring after the pathologist had reviewed the specimen at the regional laboratory. Because of these delays, only 22% of patients biopsied were ever informed of their results. By performing this audit, reporting the results, and acting against the problems discovered, the service rapidly improved. This study illustrates the importance of simple, routine audit in district hospitals in developing countries.

Biopsy↗