Adverse drug reactions of Highly Active Antiretroviral Therapy (HAART) in HIV infected patients at the General Hospital, Douala, Cameroon: A cross sectional study

Background: The use of highly active antiretroviral therapy (HAART) as the main option for management of people living with Human Immunedeficiency virus (HIV) is associated with decrease morbidity and mortality. This is due to its effectiveness in inhibiting viral replication. However thiseffectiveness is not without adverse drug effects which in many settings are not monitored. Methods: A cross sectional clinical chart review ofadult Cameroonian patients on HAART between 2003 and 2009 at the Douala General Hospital was done in search of reported HAART-associatedAdverse Drug effects (ADRs). The prevalence of ADR defined as the proportion of the study population with ADR was determined and stratified by age, sex, weight and HAART regimen.Results: Sixty-six (19.5%) of the 339 patients on HAART reported ADRs. Among those who reported ADRs, 29.6% were on D4T-3TC-EFV, 29.3% on D4T-3TC-NVP, 16% on AZT-3TC-EFV and 10.8% on AZT-3TC-NVP. Peripheral Neuropathy was the most common ADR and represented 21.2% of all ADRs. Patients on D4T containing regimens were more likely to develop ADR (OR = 3.5, 95% CI 1.5 –9.8, p<0.01) and 56.1% of all ADRs were associated to D4T. Hospital admissions were for patients with severe anaemia, no fatal cases of ADRs were recorded. Conclusion: HAART-associated ADRs are common and therefore should be actively looked for by caregivers so as to ameliorate the quality of life of HIV patients on treatment.Key words: Adverse drug reaction, HAART, HI

Adiponectin levels and its relation with insulin secretion and insulin sensitivity in a group of sub-Saharan African women with polycystic ovary syndrome.

Low levels of adiponectin have been reported in Polycystic Ovary Syndrome (PCOS). In sub-Saharan Africa, little data are available on the topic. We aimed to investigate the levels of adiponectin and its relation with insulin secretion and insulin sensitivity in women with PCOS in Yaoundé, Cameroon. A comparative cross-sectional study was conducted in 32 women presenting PCOS and 32 controls matched for age and Body Mass Index. For each participant, adiponectin levels were measured. We estimated insulin sensitivity using Homeostasis model index (HOMA-IR) and insulin secretion with C-peptide levels. Women with PCOS had higher insulin secretion levels than controls (C-peptide: 4.98 ± 3.83 vs 3.25 ± 1.62 mUI/l; p = 0.02). Also, the HOMA-IR index was higher compared to that of women without PCOS (1.15 ± 0.90 vs 0.77 ± 0.38; p = 0.03) suggesting greater insulin resistance. The median [25th-75th percentile] values of adiponectin concentrations were similar between the two groups (22.68 [21.72-23.41] μg/ml vs 22.03 [21.40-22.93] μg/ml; p = 0.1). There was no association between insulin sensitivity and adiponectin levels in the PCOS group. PCOS is not associated with changes in adiponectin in a population of sub-Saharan African women. Further studies are needed to shed more light on this condition

Fasting insulin sensitivity indices are not better than routine clinical variables at predicting insulin sensitivity among Black Africans: a clamp study in sub-Saharan Africans

BACKGROUND: We aimed to evaluate the predictive utility of common fasting insulin sensitivity indices, and non-laboratory surrogates [BMI, waist circumference (WC) and waist-to-height ratio (WHtR)] in sub-Saharan Africans without diabetes. METHODS: We measured fasting glucose and insulin, and glucose uptake during 80/mU/m2/min euglycemic clamp in 87 Cameroonians (51 men) aged (SD) 34.6 (11.4) years. We derived insulin sensitivity indices including HOMA-IR, quantitative insulin sensitivity check index (QUICKI), fasting insulin resistance index (FIRI) and glucose-to-insulin ratio (GIR). Indices and clinical predictors were compared to clamp using correlation tests, robust linear regressions and agreement of classification by sex-specific thirds. RESULTS: The mean insulin sensitivity was M =10.5+/-3.2mg/kg/min. Classification across thirds of insulin sensitivity by clamp matched with non-laboratory surrogates in 30-48% of participants, and with fasting indices in 27-51%, with kappa statistics ranging from 0.10 to 0.26. Fasting indices correlated significantly with clamp (/r/=0.23-0.30), with GIR performing less well than fasting insulin and HOMA-IR (both p <0.02). BMI, WC and WHtR were equal or superior to fasting indices (/r/=0.38-0.43). Combinations of fasting indices and clinical predictors explained 25-27% of variation in clamp values. CONCLUSION: Fasting insulin sensitivity indices are modest predictors of insulin sensitivity measured by euglycemic clamp, and do not perform better than clinical surrogates in this population

Human Herpesvirus 8 (HHV8) Sequentially Shapes the NK Cell Repertoire during the Course of Asymptomatic Infection and Kaposi Sarcoma

The contribution of innate immunity to immunosurveillance of the oncogenic Human Herpes Virus 8 (HHV8) has not been studied in depth. We investigated NK cell phenotype and function in 70 HHV8-infected subjects, either asymptomatic carriers or having developed Kaposi's sarcoma (KS). Our results revealed substantial alterations of the NK cell receptor repertoire in healthy HHV8 carriers, with reduced expression of NKp30, NKp46 and CD161 receptors. In addition, down-modulation of the activating NKG2D receptor, associated with impaired NK-cell lytic capacity, was observed in patients with active KS. Resolution of KS after treatment was accompanied with restoration of NKG2D levels and NK cell activity. HHV8-latently infected endothelial cells overexpressed ligands of several NK cell receptors, including NKG2D ligands. The strong expression of NKG2D ligands by tumor cells was confirmed in situ by immunohistochemical staining of KS biopsies. However, no tumor-infiltrating NK cells were detected, suggesting a defect in NK cell homing or survival in the KS microenvironment. Among the known KS-derived immunoregulatory factors, we identified prostaglandin E2 (PGE2) as a critical element responsible for the down-modulation of NKG2D expression on resting NK cells. Moreover, PGE2 prevented up-regulation of the NKG2D and NKp30 receptors on IL-15-activated NK cells, and inhibited the IL-15-induced proliferation and survival of NK cells. Altogether, our observations are consistent with distinct immunoevasion mechanisms that allow HHV8 to escape NK cell responses stepwise, first at early stages of infection to facilitate the maintenance of viral latency, and later to promote tumor cell growth through suppression of NKG2D-mediated functions. Importantly, our results provide additional support to the use of PGE2 inhibitors as an attractive approach to treat aggressive KS, as they could restore activation and survival of tumoricidal NK cells

Selection of the appropriate method for the assessment of insulin resistance

Insulin resistance is one of the major aggravating factors for metabolic syndrome. There are many methods available for estimation of insulin resistance which range from complex techniques down to simple indices. For all methods of assessing insulin resistance it is essential that their validity and reliability is established before using them as investigations. The reference techniques of hyperinsulinaemic euglycaemic clamp and its alternative the frequently sampled intravenous glucose tolerance test are the most reliable methods available for estimating insulin resistance. However, many simple methods, from which indices can be derived, have been assessed and validated e.g. homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI). Given the increasing number of simple indices of IR it may be difficult for clinicians and researchers to select the most appropriate index for their studies. This review therefore provides guidelines and advices which must be considered before proceeding with a study

Impact of diabetes mellitus on clinical presentation and prognosis of pancreatic cancer.

International audienceINTRODUCTION: The aim of this study was to investigate possible effects of diabetes mellitus on clinical manifestations and prognosis of pancreatic cancer (PC). PATIENTS AND METHODS: We retrospectively reviewed the clinical files of 122 patients with PC, and divided them into two groups: those with diabetes (56 patients) and those without diabetes (66 patients). The two groups were then compared for demographic profiles, clinical manifestations of PC, features of the tumor and fatal outcomes. RESULTS: Mean age, sex distribution, body mass index at cancer diagnosis, prevalence of hypertension, dyslipidemia, weight loss, abdominal pain, lumbar pain, signs of dyspepsia, and size, and histological features of the tumor were similar between the two groups. The cancer was located in the head of the pancreas in 50% of those with diabetes, and 80% of those without diabetes (P=0.04). The median survival time was similar. CONCLUSIONS: Clinical features, tumor size and prognosis of PC are similar in people with and without diabetes. Having diabetes does not seem to contribute to earlier diagnosis of PC