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1.
J Antimicrob Chemother ; 76(3): 718-721, 2021 02 11.
Article in English | MEDLINE | ID: mdl-33241266

ABSTRACT

BACKGROUND: The use of rifamycin antibiotics for TB prevention carries a risk of detrimental drug-drug interactions with concomitantly used ART. OBJECTIVES: To evaluate the interaction of the antiretroviral drug nevirapine in combination with 4 weeks of daily rifapentine and isoniazid for TB prevention in people living with HIV. METHODS: Participants were individuals enrolled in the BRIEF-TB study receiving nevirapine and randomized to the rifapentine/isoniazid arm of the study. Participants provided sparse pharmacokinetic (PK) sampling at baseline and weeks 2 and 4 for trough nevirapine determination. Nevirapine apparent oral clearance (CL/F) was estimated and the geometric mean ratio (GMR) of CL/F prior to and during rifapentine/isoniazid was calculated. RESULTS: Seventy-eight participants had evaluable PK data: 61 (78%) female, 51 (65%) black non-Hispanic and median (range) age of 40 (13-66) years. Median (IQR) nevirapine trough concentrations were: week 0, 7322 (5266-9302) ng/mL; week 2, 5537 (3552-8462) ng/mL; and week 4, 5388 (3516-8243) ng/mL. Sixty out of 78 participants (77%) had nevirapine concentrations ≥3000 ng/mL at both week 2 and 4. Median (IQR) nevirapine CL/F values were: week 0 pre-rifapentine/isoniazid, 2.03 (1.58-2.58) L/h; and during rifapentine/isoniazid, 2.62 (1.81-3.42) L/h. The GMR (90% CI) for nevirapine CL/F was 1.30 (1.26-1.33). CONCLUSIONS: The CL/F of nevirapine significantly increased with concomitant rifapentine/isoniazid. The decrease in nevirapine trough concentrations during rifapentine/isoniazid therapy suggests induction of nevirapine metabolism, consistent with known rifapentine effects. The magnitude of this drug-drug interaction suggests daily rifapentine/isoniazid for TB prevention should not be co-administered with nevirapine-containing ART.


Subject(s)
Anti-HIV Agents , HIV Infections , Adolescent , Adult , Aged , Anti-HIV Agents/therapeutic use , Antitubercular Agents/therapeutic use , Female , HIV Infections/drug therapy , HIV Infections/prevention & control , Humans , Isoniazid/therapeutic use , Male , Middle Aged , Nevirapine/therapeutic use , Rifampin/analogs & derivatives , Young Adult
2.
Afr. j. health prof. educ ; 9(3): 138-143, 2017.
Article in English | AIM (Africa) | ID: biblio-1256941

ABSTRACT

Background. The University of Zimbabwe College of Health Sciences (UZCHS), Harare, which has a long tradition of community-based education (CBE), has not been evaluated since 1991. An innovative approach was used to evaluate the programme during 2015.Objectives. To evaluate the CBE programme, using a peer-review model of evaluation and simultaneously introducing and orientating participating colleagues from other medical schools in southern Africa to this review process.Methods. An international team of medical educators, convened through the Medical Education Partnership Initiative, worked collaboratively to modify an existing peer-review assessment method. Data collection took the form of pre-visit surveys, on-site and field-visit interviews with key informants, a review of supporting documentation and a post-review visit.Results. All 5 years of the medical education curriculum at UZCHS included some form of CBE that ranged from community exposure in the 1st year to district hospital-based clinical rotations during the clinical years. Several strengths, including the diversity of community-based activities and the availability of a large teaching platform, were identified. However, despite the expression of satisfaction with the programme, the majority of students indicated that they do not plan to work in rural areas in Zimbabwe. Several key recommendations were offered, central to which was strengthening the academic co-ordination of the programme and curriculum renewal in the context of the overall MB ChB curriculum.Conclusion. This evaluation demonstrated the value of peer review to bring a multidimensional, objective assessment to a CBE programme


Subject(s)
Curriculum , Peer Review , Students, Medical , Universities , Zimbabwe
3.
J Neurovirol ; 22(4): 472-8, 2016 08.
Article in English | MEDLINE | ID: mdl-26733457

ABSTRACT

Infrastructure for conducting neurological research in resource-limited settings (RLS) is limited. The lack of neurological and neuropsychological (NP) assessment and normative data needed for clinical interpretation impedes research and clinical care. Here, we report on ACTG 5271, which provided neurological training of clinical site personnel and collected neurocognitive normative comparison data in diverse settings. At ten sites in seven RLS countries, we provided training for NP assessments. We collected normative comparison data on HIV- participants from Brazil (n = 240), India (n = 480), Malawi (n = 481), Peru (n = 239), South Africa (480), Thailand (n = 240), and Zimbabwe (n = 240). Participants had a negative HIV test within 30 days before standardized NP exams were administered at baseline and 770 at 6 months. Participants were enrolled in eight strata, gender (female and male), education (<10 and ≥10 years), and age (<35 and ≥35 years). Of 2400 enrolled, 770 completed the 6-month follow-up. As expected, significant between-country differences were evident in all the neurocognitive test scores (p < 0.0001). There was variation between the age, gender, and education strata on the neurocognitive tests. Age and education were important variables for all tests; older participants had poorer performance, and those with higher education had better performance. Women had better performance on verbal learning/memory and speed of processing tests, while men performed better on motor tests. This study provides the necessary neurocognitive normative data needed to build infrastructure for future neurological and neurocognitive studies in diverse RLS. These normative data are a much-needed resource for both clinicians and researchers.


Subject(s)
Clinical Trials as Topic , Cognition/physiology , Health Personnel/education , Mental Status and Dementia Tests , Adult , Africa , Age Factors , Asia , Cognitive Dysfunction/complications , Cognitive Dysfunction/psychology , Developing Countries/economics , Educational Status , Female , HIV Infections/complications , HIV Infections/psychology , Healthy Volunteers , Humans , Male , Middle Aged , Reference Values , Sex Factors , South America , Verbal Learning/physiology
4.
BMC Health Serv Res ; 15: 527, 2015 Nov 28.
Article in English | MEDLINE | ID: mdl-26615587

ABSTRACT

BACKGROUND: Decentralization of ART services scaled up significantly with the country wide roll out of option B plus in Uganda. Little work has been undertaken to examine population level access to HIV care particularly in hard to reach areas in rural Africa. Most work on ART scale up has been done at health facility level which omits people not accessing healthcare in the community. This study describes health service usage, particularly HIV testing and care in 2/6 parishes of Lapono sub-county of northern Uganda, prior to introduction of ART services in Lira Kato Health Centre (a local lower-level health centre III), as part of ART decentralization. METHODS: Household and individual questionnaires were administered to household members (aged 15-59 years). Logit random effects models were used to test for differences in proportions (allowing for clustering within villages). RESULTS: 2124 adults from 1351 households were interviewed (755 [36%] males, 1369 [64 %] females). 2051 (97%) participants reported seeking care locally for fever, most on foot and over half at Lira Kato Health Centre. 574 (76%) men and 1156 (84%) women reported ever-testing for HIV (P < 0.001 for difference); 34/574 (6%) men and 102/1156 (9%) women reported testing positive (P = 0.04). 818/850 (96%) women who had given birth in the last 5 years had attended antenatal care in their last pregnancy: 7 women were already diagnosed with HIV (3 on ART) and 790 (97%) reported being tested for HIV (34 tested newly positive). 124/136 (91%) HIV-positive adults were in HIV-care, 123/136 (90 %) were taking cotrimoxazole and 74/136 (54%) were on ART. Of adults in HIV-care, most were seen at Kalongo hospital (n = 87), Patongo Health Centre (n = 7) or Lira Kato Health Centre (n = 23; no ART services). 58/87, 5/7 and 20/23 individuals walked to Kalongo hospital (56 km round-trip, District Health Office information), Patongo Health Centre (76 km round-trip, District Health Office information) and Lira Kato Health Centre (local) respectively. 8 HIV-infected children were reported; only 2 were diagnosed aged <24 months: 7/8 were in HIV-care including 3 on ART. CONCLUSIONS: Higher proportions of women compared to men reported ever-testing for HIV and testing HIV-positive, similar to other surveys. HIV-infected men and women travelled considerable distances for ART services. Children appeared to be under-accessing testing and referral for treatment. Decentralization of ART services to a local health facility would decrease travel time and transport costs, making care and treatment more easily accessible.


Subject(s)
Anti-Retroviral Agents , HIV Infections/diagnosis , Health Services/statistics & numerical data , Politics , Rural Population , Adolescent , Adult , Africa , Female , Humans , Legislation, Drug , Male , Middle Aged , Pregnancy , Prenatal Care , Surveys and Questionnaires , Travel/economics , Uganda , Young Adult
5.
S Afr Med J ; 105(5): 384-8, 2015 Jun 05.
Article in English | MEDLINE | ID: mdl-26242684

ABSTRACT

BACKGROUND: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain significant causes of morbidity and mortality in resource-limited settings. In Zimbabwe ARF/RHD characteristics have not been systematically documented. OBJECTIVES: To document cases of ARF/RHD among children presenting at referral hospitals in Harare, Zimbabwe, determine their clinical and echocardiographic characteristics, and identify opportunities for improving care. METHODS: A cross-sectional survey was carried out in which consecutive children aged 1 - 12 years presenting with ARF/RHD according to the 2002/3 World Health Organization modified Jones criteria were enrolled. RESULTS: Out of 2 601 admissions and 1 026 outpatient visits over 10 months, 50 children were recruited, including 31 inpatients with ARF/RHD and 19 outpatients with chronic RHD. Among inpatients, 9 had ARF only, 7 recurrent ARF with RHD, and 15 RHD only. The commonest valve lesions were mitral regurgitation (26/31) and aortic regurgitation (11/31). The commonest reason for admission was cardiac failure (22/31). The proportion of ARF/RHD cases among inpatients aged 1 - 12 years was 11.9/1 000. Of the 22 with RHD, 14 (63.6%) presented de novo and 1 had bacterial endocarditis. Among the outpatients, 15 had cardiac failure while echocardiographic findings included mitral regurgitation (18/19) and aortic regurgitation (5/19). At presentation, 18/26 known cases were on oral penicillin prophylaxis and 7 on injectable penicillin. Of those on secondary prophylaxis, 68.0% reported taking it regularly. CONCLUSION: ARF/RHD remains a major problem and cause of hospital admissions in Harare, Zimbabwe. Children often present late with established RHD and cardiac failure. With the majority on oral penicillin, secondary prophylaxis was suboptimal in a resource-limited setting unable to offer valve replacement surgery.


Subject(s)
Referral and Consultation , Rheumatic Fever/epidemiology , Rheumatic Heart Disease/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Incidence , Infant , Male , Retrospective Studies , Zimbabwe/epidemiology
6.
HIV Clin Trials ; 15(6): 246-60, 2014.
Article in English | MEDLINE | ID: mdl-25433664

ABSTRACT

BACKGROUND: Convenient dosing, potency, and low toxicity support use of tenofovir disoproxil fumarate (TDF) as preferred nucleotide reverse transcriptase inhibitor (NRTI) for HIV-1 treatment. However, renal and metabolic safety of TDF compared to other NRTIs has not been well described in resource-limited settings. METHODS: This was a secondary analysis examining the occurrence of renal abnormalities (RAs) and renal and metabolic serious non-AIDS-defining events (SNADEs) through study follow-up between participants randomized to zidovudine (ZDV)/lamivudine/ efavirenz and TDF/emtricitabine/efavirenz treatment arms within A5175/PEARLS trial. Exact logistic regression explored associations between baseline covariates and RAs. Response profile longitudinal analysis compared creatinine clearance (CrCl) over time between NRTI groups. RESULTS: Twenty-one of 1,045 participants developed RAs through 192 weeks follow-up; there were 15 out of 21 in the TDF arm (P = .08). Age 41 years or older (odds ratio [OR], 3.35; 95% CI, 1.1-13.1), his- tory of diabetes (OR, 10.7; 95% CI, 2.1-55), and lower baseline CrCl (OR, 3.1 per 25 mL/min decline; 95% CI, 1.7-5.8) were associated with development of RAs. Renal SNADEs occurred in 42 participants; 33 were urinary tract infections and 4 were renal failure/insufficiency; one event was attributed to TDF. Significantly lower CrCl values were maintained among patients receiving TDF compared to ZDV (repeated measures analysis, P = .05), however worsening CrCl from baseline was not observed with TDF exposure over time. Metabolic SNADEs were rare, but were higher in the ZDV arm (20 vs 3; P < .001). CONCLUSIONS: TDF is associated with lower serious metabolic toxicities but not higher risk of RAs, serious renal events, or worsening CrCl over time compared to ZDV in this randomized multinational study.


Subject(s)
Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV-1 , Kidney Diseases/chemically induced , Metabolic Diseases/chemically induced , Adult , Anti-HIV Agents/administration & dosage , Drug Therapy, Combination , Female , Humans , Logistic Models , Male , Middle Aged
7.
Clin Infect Dis ; 55(6): 868-76, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22661489

ABSTRACT

BACKGROUND: AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings. METHODS: Participants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine, and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations. RESULTS: The median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP test scores improved (P < .05) with the exception of semantic verbal fluency. No differences in neurological and neuropsychological functioning between treatment regimens were detected (P > .10). Significant country effects were noted on all NP tests and neurological outcomes (P < .01). CONCLUSIONS: The study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization -recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and reduce neurological dysfunction. CLINICAL TRIALS REGISTRATION: NCT00096824.


Subject(s)
AIDS Dementia Complex/epidemiology , AIDS Dementia Complex/prevention & control , Acquired Immunodeficiency Syndrome/complications , Acquired Immunodeficiency Syndrome/drug therapy , Anti-Retroviral Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , Acquired Immunodeficiency Syndrome/virology , Adult , Female , HIV-1/pathogenicity , Humans , Male , Neurologic Examination , Psychological Tests , Treatment Outcome
8.
Trop Med Int Health ; 17(5): 584-94, 2012 May.
Article in English | MEDLINE | ID: mdl-22463596

ABSTRACT

OBJECTIVES: To describe associations between different summaries of adherence in the first year on antiretroviral therapy (ART) and the subsequent risk of mortality, to identify patients at high risk because of early adherence behaviour. METHODS: We previously described an approach where adherence behaviour at successive clinic visits during the first year on ART was seen as a Markov chain (MC), and the individually estimated transition probabilities between 'good', 'poor' and 'non-response' adherence states were used to classify HIV-infected adults in the DART trial into subgroups with similar behaviour. The impact of this classification and classifications based on traditional 'averaged' measures [mean drug possession ratio (DPR) and self-reported adherence] were compared in terms of their impact on longer-term mortality over the 2-5 years on ART using Cox proportional hazards models. RESULTS: Of 2960 participants in follow-up after 1 year on ART, 29% had never missed pills in the last month and 11% had 100% DPR throughout the first year. The poorest adherers by self-reported measures were more likely to have only none/primary education (P < 0.01). Being in the poorest adherence subgroup by MC and DPR was independently associated with increased mortality [HR = 1.57 (95% CI 1.02, 2.42); 1.82 (1.32, 2.51) respectively]. CONCLUSIONS: Classification based on dynamic adherence behaviour is associated with mortality independently of DPR. The classifications could be useful in understanding adherence, targeting focused interventions and improving longer-term adherence to therapy.


Subject(s)
Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , HIV Infections/drug therapy , Patient Compliance/statistics & numerical data , Adult , Female , Follow-Up Studies , HIV Infections/immunology , Humans , Male , Markov Chains , Proportional Hazards Models , Surveys and Questionnaires , Treatment Outcome , Uganda , Zimbabwe
9.
Lancet ; 375(9722): 1278-86, 2010 Apr 10.
Article in English | MEDLINE | ID: mdl-20347483

ABSTRACT

BACKGROUND: Co-trimoxazole prophylaxis can reduce mortality from untreated HIV infection in Africa; whether benefits occur alongside combination antiretroviral therapy (ART) is unclear. We estimated the effect of prophylaxis after ART initiation in adults. METHODS: Participants in our observational analysis were from the DART randomised trial of management strategies in HIV-infected, symptomatic, previously untreated African adults starting triple-drug ART with CD4 counts lower than 200 cells per muL. Co-trimoxazole prophylaxis was not routinely used or randomly allocated, but was variably prescribed by clinicians. We estimated effects on clinical outcomes, CD4 cell count, and body-mass index (BMI) using marginal structural models to adjust for time-dependent confounding by indication. DART was registered, number ISRCTN13968779. FINDINGS: 3179 participants contributed 14 214 years of follow-up (8128 [57%] person-years on co-trimoxazole). Time-dependent predictors of co-trimoxazole use were current CD4 cell count, haemoglobin concentration, BMI, and previous WHO stage 3 or 4 events on ART. Present prophylaxis significantly reduced mortality (odds ratio 0.65, 95% CI 0.50-0.85; p=0.001). Mortality risk reduction on ART was substantial to 12 weeks (0.41, 0.27-0.65), sustained from 12-72 weeks (0.56, 0.37-0.86), but not evident subsequently (0.96, 0.63-1.45; heterogeneity p=0.02). Variation in mortality reduction was not accounted for by time on co-trimoxazole or current CD4 cell count. Prophylaxis reduced frequency of malaria (0.74, 0.63-0.88; p=0.0005), an effect that was maintained with time, but we observed no effect on new WHO stage 4 events (0.86, 0.69-1.07; p=0.17), CD4 cell count (difference vs non-users, -3 cells per muL [-12 to 6]; p=0.50), or BMI (difference vs non-users, -0.04 kg/m(2) [-0.20 to 0.13); p=0.68]. INTERPRETATION: Our results reinforce WHO guidelines and provide strong motivation for provision of co-trimoxazole prophylaxis for at least 72 weeks for all adults starting combination ART in Africa. FUNDING: UK Medical Research Council, the UK Department for International Development, the Rockefeller Foundation, GlaxoSmithKline, Gilead Sciences, Boehringer-Ingelheim, and Abbott Laboratories.


Subject(s)
AIDS-Related Opportunistic Infections/prevention & control , Anti-Infective Agents/administration & dosage , Anti-Retroviral Agents/administration & dosage , CD4 Lymphocyte Count , HIV Infections/immunology , Trimethoprim, Sulfamethoxazole Drug Combination/administration & dosage , Adult , Drug Administration Schedule , Drug Combinations , Drug Therapy, Combination , HIV Infections/drug therapy , HIV Infections/mortality , Humans , Randomized Controlled Trials as Topic , Uganda , Zimbabwe
10.
Lancet ; 375(9709): 123-31, 2010 Jan 09.
Article in English | MEDLINE | ID: mdl-20004464

ABSTRACT

BACKGROUND: HIV antiretroviral therapy (ART) is often managed without routine laboratory monitoring in Africa; however, the effect of this approach is unknown. This trial investigated whether routine toxicity and efficacy monitoring of HIV-infected patients receiving ART had an important long-term effect on clinical outcomes in Africa. METHODS: In this open, non-inferiority trial in three centres in Uganda and one in Zimbabwe, 3321 symptomatic, ART-naive, HIV-infected adults with CD4 counts less than 200 cells per microL starting ART were randomly assigned to laboratory and clinical monitoring (LCM; n=1659) or clinically driven monitoring (CDM; n=1662) by a computer-generated list. Haematology, biochemistry, and CD4-cell counts were done every 12 weeks. In the LCM group, results were available to clinicians; in the CDM group, results (apart from CD4-cell count) could be requested if clinically indicated and grade 4 toxicities were available. Participants switched to second-line ART after new or recurrent WHO stage 4 events in both groups, or CD4 count less than 100 cells per microL (LCM only). Co-primary endpoints were new WHO stage 4 HIV events or death, and serious adverse events. Non-inferiority was defined as the upper 95% confidence limit for the hazard ratio (HR) for new WHO stage 4 events or death being no greater than 1.18. Analyses were by intention to treat. This study is registered, number ISRCTN13968779. FINDINGS: Two participants assigned to CDM and three to LCM were excluded from analyses. 5-year survival was 87% (95% CI 85-88) in the CDM group and 90% (88-91) in the LCM group, and 122 (7%) and 112 (7%) participants, respectively, were lost to follow-up over median 4.9 years' follow-up. 459 (28%) participants receiving CDM versus 356 (21%) LCM had a new WHO stage 4 event or died (6.94 [95% CI 6.33-7.60] vs 5.24 [4.72-5.81] per 100 person-years; absolute difference 1.70 per 100 person-years [0.87-2.54]; HR 1.31 [1.14-1.51]; p=0.0001). Differences in disease progression occurred from the third year on ART, whereas higher rates of switch to second-line treatment occurred in LCM from the second year. 283 (17%) participants receiving CDM versus 260 (16%) LCM had a new serious adverse event (HR 1.12 [0.94-1.32]; p=0.19), with anaemia the most common (76 vs 61 cases). INTERPRETATION: ART can be delivered safely without routine laboratory monitoring for toxic effects, but differences in disease progression suggest a role for monitoring of CD4-cell count from the second year of ART to guide the switch to second-line treatment. FUNDING: UK Medical Research Council, the UK Department for International Development, the Rockefeller Foundation, GlaxoSmithKline, Gilead Sciences, Boehringer-Ingelheim, and Abbott Laboratories.


Subject(s)
Anti-Retroviral Agents/therapeutic use , Drug Monitoring , HIV Infections/drug therapy , Adenine/analogs & derivatives , Adenine/therapeutic use , Adolescent , Adult , Africa/epidemiology , Aged , Anemia/epidemiology , CD4 Lymphocyte Count , Creatinine/analysis , Dideoxynucleosides/therapeutic use , Disease Progression , Female , Glomerular Filtration Rate , HIV Infections/classification , HIV Infections/mortality , HIV-1/genetics , HIV-Associated Lipodystrophy Syndrome/epidemiology , Hemoglobins/analysis , Humans , Lamivudine/therapeutic use , Male , Middle Aged , Neutropenia/epidemiology , Neutrophils/metabolism , Nevirapine/therapeutic use , Organophosphonates/therapeutic use , RNA, Viral/metabolism , Tenofovir , Urea/analysis , Viral Load , Zidovudine/therapeutic use
11.
12.
J Urol ; 172(5 Pt 1): 1925, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15540756
13.
Cent Afr J Med ; 50(3-4): 24-9, 2004.
Article in English | MEDLINE | ID: mdl-15490713

ABSTRACT

OBJECTIVE: The main aim of the study was to determine the prevalence of metabolic syndrome disorders and their interrelations in black Zimbabwean type 2 diabetic patients. STUDY DESIGN: Prospective cross sectional study. SETTING: Outpatient diabetic clinics at Harare and Parirenyatwa tertiary hospitals. MAIN OUTCOME MEASURES: We recruited 109 adult diabetic subjects attending a tertiary hospital Diabetic Clinic. Anthropometric and metabolic parameters were measured by standard methods. Eighty percent of the patients were hypertensive, 32% dyslipidaemic, 32% obese, 50% hyperinsulinaemic, 61% had poor glycaemic control and 43% of the participants had the metabolic syndrome. The means of BMI and triglycerides were significantly different in hyperinsulinaemic versus non-hyperinsulinaemic patients (p < 0.001 and 0.041 respectively), and diastolic blood pressure was significantly raised in the obese group (p = 0.043). The following significant associations were observed, hyperinsulinaemia with the metabolic syndrome (odds ratio = 3.9, p < 0.001) as well with obesity (odds ratio = 4.8, p < 0.001), however, only a weak association was observed between hypertension and hyperinsulinaemia (odds ratio = 2.5, p = 0.064). Patients exhibiting three metabolic disorders (dyslipidaemia, hypertension and obesity) were five times more likely to be hyperinsulinaemic (p = 0.025) and hypertensive patients were almost three times more likely to be hyperinsulinaemic. CONCLUSION: In comparison to their counterparts from certain ethnic groups, this urban diabetic population is also burdened with a variety of metabolic disorders which are risk factors for coronary artery disease. In this population, hyperinsulinaemia has a relatively weak association with hypertension and the relationship between obesity versus diastolic blood pressure as well as hypertriglyceridaemia versus serum insulin levels requires further investigation.


Subject(s)
Diabetes Mellitus, Type 2/complications , Metabolic Syndrome/epidemiology , Urban Health/statistics & numerical data , Black People/statistics & numerical data , Cross-Sectional Studies , Diabetes Mellitus, Type 2/ethnology , Female , Humans , Male , Metabolic Syndrome/complications , Metabolic Syndrome/ethnology , Middle Aged , Outpatient Clinics, Hospital/statistics & numerical data , Prevalence , Prospective Studies , Risk Factors , Zimbabwe/epidemiology
14.
Urology ; 60(1): 125-9, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12100937

ABSTRACT

OBJECTIVES: To evaluate the screening patterns of primary care physicians with regard to erectile dysfunction (ED). METHODS: A prospective study was performed using an institutional review board-approved Sexual Health Inventory for Men questionnaire of male patients presenting to a university-based urology clinic. The data were compiled and analyzed with descriptive statistics using Statistical Package for Social Sciences, version 10.0, software. RESULTS: Of 140 patients, 102 completed and returned the survey. Of these patients, 93% were white. Twenty-five percent were between the ages of 40 and 50 years, 20% were between the ages of 51 and 60 years, and 24% were between the ages of 60 and 70 years. The average number of risk factors for ED identified in the patient population was 2.1. Fifty-six percent of patients had a Sexual Health Inventory for Men score of 21 or less, indicative of an element of ED. Eighty-three percent had primary care physicians; 23% of patients with a primary care physician were screened for ED. Of those screened, 58% of patients initiated the discussion with their physician. CONCLUSIONS: Screening for ED, using the Sexual Health Inventory for Men instrument, should be performed on patients with any identifiable risk factor. Screening is appropriate because effective treatment of ED is available and because ED can be associated with occult cardiac disease.


Subject(s)
Erectile Dysfunction/diagnosis , Adult , Age Factors , Aged , Cardiovascular Diseases/epidemiology , Comorbidity , Erectile Dysfunction/epidemiology , Health Status , Humans , Male , Mass Screening/standards , Medical History Taking/statistics & numerical data , Middle Aged , Primary Health Care/statistics & numerical data , Quality Control , Risk Factors , Surveys and Questionnaires
15.
Tex Heart Inst J ; 28(1): 47-52, 2001.
Article in English | MEDLINE | ID: mdl-11330742

ABSTRACT

Severe mitral valve regurgitation due to systemic lupus erythematosus is a rare cause of valvular heart disease, necessitating valve surgery. Currently, there are 36 case reports in the world medical literature of mitral valve replacement or repair in patients who have lupus. The current trend in mitral valve surgery is toward anatomic valve repair. In patients who have systemic lupus erythematosus, however, valve repair often leads to repeat surgery and valve replacement. We report the cases of 5 patients with lupus and severe mitral valve regurgitation who underwent mitral valve surgery. In 3 of these patients, replacement with a mechanical prosthetic mitral valve was performed with good long-term results. In the other 2 patients, mitral valve repair was performed, but only 1 of the repairs was successful. The 2nd patient required subsequent replacement with a mechanical valve. To our knowledge, this report of 5 patients is the largest series of mitral valve surgery in patients with lupus. These results, along with a review of the literature, suggest the superiority of mechanical prosthetic valve replacement to repair in patients who have systemic lupus erythematosus.


Subject(s)
Heart Valve Prosthesis Implantation , Lupus Erythematosus, Systemic/surgery , Mitral Valve Insufficiency/surgery , Mitral Valve/surgery , Postoperative Complications/surgery , Adult , Female , Follow-Up Studies , Humans , Middle Aged , Reoperation , Treatment Outcome
16.
Clin Infect Dis ; 32(8): 1235-6, 2001 Apr 15.
Article in English | MEDLINE | ID: mdl-11283816

ABSTRACT

Cryptococcus neoformans is associated with as much as 45% of meningitis in patients admitted for hospital care in Zimbabwe, and it is an important opportunistic infection in patients infected with the human immunodeficiency virus. Cases of cryptococcosis presenting as a spinal cord syndrome have been reported from Zimbabwe and South Africa, but these were all cases of Cryptococcus vertebral osteomyelitis. We describe 3 unusual patients who presented with a myelitis-like syndrome without vertebral osteomyelitis.


Subject(s)
AIDS-Related Opportunistic Infections/physiopathology , Cryptococcosis/physiopathology , Myelitis/physiopathology , AIDS-Related Opportunistic Infections/drug therapy , Adult , Cryptococcosis/drug therapy , Cryptococcus neoformans , Female , Humans , Male , Myelitis/drug therapy , Syndrome
17.
J Clin Virol ; 20(3): 99-109, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11166656

ABSTRACT

BACKGROUND: in response to a variety of stimuli, phagocytes release large quantities of reactive oxygen species (ROS), which are essential for bacterial killing. However, excessive ROS production not appropriately compensated by antioxidant molecules can lead to oxidative stress, which may also play an important role in pathogenesis of HIV infection. In fact, ROS participate in chronic inflammation, HIV replication and the apoptosis of cells of the immune system. OBJECTIVE AND STUDY DESIGN: we used flow cytometry to study, in whole blood, the activation and redox status of polymorphonuclear neutrophils (PMN) and monocytes at different stages of the disease. RESULTS: we showed that neutrophils and monocytes from HIV-infected patients spontaneously produced increased amounts of H2O2. This increased H2O2 production was associated with alterations of adhesion molecules expression at the cell surface, which also reflected basal activation of phagocytes from the HIV-infected patients. In monocytes, basal H2O2 production correlated with viral load. This increased ROS production was associated with changes in the expression of the antiapoptotic/antioxidant compounds Bcl-2 and thioredoxin along the course of the disease. This modulation could result from a dual regulation by oxidative stress and could explain at least in part why monocyte numbers remain relatively stable throughout the disease. Monocytes expressed a normal maximal capacity to produce ROS in optimal conditions of stimulation. In contrast, after ex vivo priming with TNFalpha or IL-8, neutrophils showed a decreased H2O2 production in response to bacterial N-formyl peptides. This latter impairment correlated with the decrease in CD4+ lymphocyte numbers and with IL-8 and IL-6 plasma levels. CONCLUSIONS: the increased basal ROS production by phagocytes could participate to the oxidative injury which has been implicated in the pathophysiology of HIV infection. In addition, the decreased priming of H2O2 production by neutrophils could contribute to the increased susceptibility of HIV-infected patients to bacterial infections.


Subject(s)
HIV Seropositivity/immunology , HIV-1 , Monocytes/metabolism , Neutrophils/metabolism , Oxidative Stress , Actins/blood , Adult , Cytokines/blood , Flow Cytometry , HIV Seropositivity/blood , Humans , Hydrogen Peroxide/blood , L-Selectin/blood , Lipopolysaccharide Receptors/blood , Macrophage-1 Antigen/blood , Neutrophil Activation , Oxidation-Reduction , Proto-Oncogene Proteins c-bcl-2/blood , Reactive Oxygen Species/metabolism , Thioredoxins/blood
18.
J Immunol ; 166(2): 1206-13, 2001 Jan 15.
Article in English | MEDLINE | ID: mdl-11145703

ABSTRACT

Generation of superoxide anion by the multiprotein complex NADPH phagocyte oxidase is accompanied by extensive phosphorylation of its 47-kDa protein component, p47(phox), a major cytosolic component of this oxidase. Protein kinase C zeta (PKC zeta), an atypical PKC isoform expressed abundantly in human polymorphonuclear leukocytes (PMN), translocates to the PMN plasma membrane upon stimulation by the chemoattractant fMLP. We investigated the role of PKC zeta in p47(phox) phosphorylation and in superoxide anion production by human PMN. In vitro incubation of recombinant p47(phox) with recombinant PKC zeta induced a time- and concentration-dependent phosphorylation of p47(phox) with an apparent K(m) value of 2 microM. Phosphopeptide mapping analysis of p47(phox) showed that PKC zeta phosphorylated fewer selective sites in comparison to "conventional" PKCs. Serine 303/304 and serine 315 were identified as targets of PKC zeta by site-directed mutagenesis. Stimulation of PMN by fMLP induced a rapid and sustained plasma membrane translocation of PKC zeta that correlated to that of p47(phox). A cell-permeant-specific peptide antagonist of PKC zeta inhibited both fMLP-induced phosphorylation of p47(phox) and its membrane translocation. The antagonist also inhibited the fMLP-induced production of oxidant (IC(50) of 10 microM), but not that induced by PMA. The inhibition of PKC zeta expression in HL-60 neutrophil-like cells using antisense oligonucleotides (5 and 10 microM) inhibited fMLP-promoted oxidant production (27 and 50%, respectively), but not that induced by PMA. In conclusion, p47(phox) is a substrate for PKC zeta and participates in the signaling cascade between fMLP receptors and NADPH oxidase activation.


Subject(s)
N-Formylmethionine Leucyl-Phenylalanine/pharmacology , NADPH Oxidases/blood , Neutrophils/enzymology , Phosphoproteins/blood , Protein Kinase C/blood , Respiratory Burst , Amino Acid Sequence , Cell Fractionation , Cell Membrane/metabolism , Enzyme Activation/genetics , Enzyme Activation/immunology , Enzyme Inhibitors/pharmacology , HL-60 Cells , Humans , Isoenzymes/antagonists & inhibitors , Isoenzymes/blood , Isoenzymes/genetics , Molecular Sequence Data , N-Formylmethionine Leucyl-Phenylalanine/blood , Neutrophil Activation/immunology , Neutrophils/metabolism , Peptide Mapping , Peptides/pharmacology , Phosphopeptides/blood , Phosphorylation , Protein Kinase C/antagonists & inhibitors , Protein Kinase C/genetics , RNA, Antisense/pharmacology , Respiratory Burst/immunology , Signal Transduction/genetics , Signal Transduction/immunology
20.
AIDS ; 14(10): 1401-7, 2000 Jul 07.
Article in English | MEDLINE | ID: mdl-10930155

ABSTRACT

OBJECTIVE: To determine the causative organisms and characteristics of patients presenting with features of meningitis. DESIGN: A prospective cross-sectional study. SETTING: Two tertiary university-affiliated hospitals in Harare, Zimbabwe. PATIENTS: Four-hundred and six patients clinically suspected to have meningitis. MAIN OUTCOME MEASURES: Causative organisms of meningitis; clinical and cerebrospinal fluid characteristics. RESULTS: Four-hundred and six predominantly adult (95% were aged > or = 18 years) patients were suspected to have meningitis. Of the 200 patients confirmed to have meningitis, 89 (45%) had cryptococcal meningitis (CM), 54 (27%) had mononuclear meningitis (MM), 31 (16%) had pyogenic meningitis (PM), 24 (12%) had tuberculous meningitis (TBM) and 2 (1%) had undefined meningitis. HIV seropositivity was 100% in CM, 83% in MM, 81% in PM and 88% in TBM patients. In-hospital mortality rate was 38.8% for CM, 34.9% for MM, 68% for PM and 66.7% for TBM. HIV seropositivity was 80% in the 206 patients not found to have meningitis. CONCLUSIONS: All patients suspected to have meningitis had a high HIV sero positivity irrespective of whether they were later confirmed to have meningitis or not. CM was the most common type of meningitis seen. In-hospital mortality was high irrespective of the cause of meningitis.


Subject(s)
HIV Infections/complications , Meningitis/complications , AIDS-Related Opportunistic Infections/cerebrospinal fluid , AIDS-Related Opportunistic Infections/complications , AIDS-Related Opportunistic Infections/immunology , Adolescent , Adult , Aged , CD4 Lymphocyte Count , Child , Cross-Sectional Studies , Female , HIV Infections/immunology , Humans , Male , Meningitis/cerebrospinal fluid , Meningitis/etiology , Meningitis, Cryptococcal/complications , Middle Aged , Prospective Studies , Tuberculosis, Meningeal/complications , Zimbabwe
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