The Neuropeptide Substance P is Elevated in Sickle Cell Disease and is a Marker of Severity of Vaso-occlusive Crisis.

Background: Acute episode of pain is the most frequent symptom for which patients with sickle cell disease (SCD) seek medical attention. The neuropeptide Substance P (SP) has been suggested as a possible aetiologic factor. This study compared the serum levels of SP in SCD subjects in painful vaso-occlusive crisis with those in steady state and normal HbAA subjects.

Late presentation of chronic myeloid leukaemia patients in a low-income country: the prognostic implications and impact on treatment outcome.

Background: In Nigeria, since 2002, Imatinib mesylate (glivec) has been available freely to chronic myeloid leukaemia (CML) patients but only at a tertiary health care centre in the southwestern part of the country. Despite this, it is not readily accessible to many patients due to the distance and other challenges including low socioeconomic status and political problems, preventing timely access to specialist care. This study evaluated the effect of the baseline characteristics on the prognostic implication and treatment outcome of CML patients in Nigeria.

Assessment of hypoxemia among young adults with sickle cell anaemia in steady state in southwestern Nigeria: a crosssectional study.

Objectives: Hypoxia is a known feature of sickle cell anaemia (SCA) which results from chronic anaemia and recurrent vaso-occlusive crisis (VOC) which can cause tissue ischaemia that leads to an end organ damage. The hallmark of SCA is chronic anaemia and recurrent vaso-occlusive crisis. The aim of this study is to compare the oxygen saturation of sickle cell anaemic individuals with the normal haemoglobin type (Hb AA) control and also to determine the prevalence of hypoxemia among SCA.

A 5-year review of research ethics applications in a tertiary health and educational institution in Nigeria.

Background: African contribution to global research output is said to be low. Poor funding and poor skills in grant writing have been suggested as important factors for this situation.

Objectives: Applications for research ethics clearance in a hospital were reviewed to have an overview of the planned studies and the proportion of them that attracted national and international funding.

Trough plasma nevirapine levels, immunologic and virologic responses in composite CYP2B6*6/*18 HIV-infected adult Nigerian patients.

The influence of composite CYP2B6*6/*18 genotype on trough plasma nevirapine levels, HIV RNA levels (virologic response) and CD4+ T lymphocyte and absolute lymphocyte counts (immunologic response) of HIV-infected patients were evaluated. Patients with records of trough plasma nevirapine levels, CD4+ T lymphocyte, absolute lymphocyte and viral load counts at baseline and months 6 and 12 after initiation of nevirapine-based antiretroviral therapy combinations were retrospectively analysed. Participants were from a cohort of 150 patients previously genotyped and with measured plasma nevirapine levels.

Distribution of Transcript Variants in Nigerians with Chronic Myeloid Leukemia.

The distribution of transcript variants e13a2 ("b2a2") and e14a2 ("b3a2") in Nigerians with chronic myeloid leukemia (CML) had not been previously studied. In addition, there is paucity of data on the impact of transcript variants on clinical presentation and survival in CML patients in Nigeria. The transcript variants were analyzed in 230 Imatinib-treated CML patients at diagnosis.

Influence of selected polymorphisms in disposition genes on lumefantrine pharmacokinetics when coadministered with efavirenz.

Background: Coadministration of artemether-lumefantrine and efavirenz has been shown to result in significant interactions. The influence of functional genetic polymorphisms in selected CYPs on the magnitude of this interaction was investigated in pregnant and nonpregnant adults.

Method: A standard 3-day regimen of artemether-lumefantrine was administered to each patient on steady-state efavirenz-based antiretroviral therapy (ART).

Association between Endothelial Dysfunction, Biomarkers of Renal Function, and Disease Severity in Sickle Cell Disease.

Background: Endothelial dysfunction (ED), as ascertained by brachial artery flow-mediated dilation (FMD), is a known feature of sickle cell disease (SCD), which is present both in crisis and in steady state. The assessment of FMD was introduced to examine the vasodilator function. Our objective was to establish the relationship between ED determined by FMD, biomarkers of renal dysfunction, and biomarkers of disease severity in SCD subjects asymptomatic of renal disease.

Differential Impact of Nevirapine on Artemether-Lumefantrine Pharmacokinetics in Individuals Stratified by c.516G>T Genotypes.

There is an increased recognition of the need to identify and quantify the impact of genetic polymorphisms on drug-drug interactions. This study investigated the pharmacogenetics of the pharmacokinetic drug-drug interaction between nevirapine and artemether-lumefantrine in HIV-positive and HIV-negative adult Nigerian subjects. Thirty each of HIV-infected patients on nevirapine-based antiretroviral therapy and HIV-negative volunteers without clinical malaria, but with predetermined c.

Portal hypertension evolving from sickled hepatopathy: Could hepatic venous Doppler ultrasound be beneficial in its evaluation?

Purpose: Sickle cell intrahepatic cholestasis involves sickling within hepatic sinusoids leading to vascular stasis and localized hypoxia resulting in ballooning of the hepatocytes causing a direct back pressure effect with resultant intracanalicular cholestasis. Vascular stasis may ultimately lead to portal hypertension. We proposed to document findings suggestive of portal hypertension evolving from hepatopathy in steady-state sickle cell disease (SCD) patients using hepatic venous Doppler ultrasound.

Intima-media thickness of the common carotid arteries as a marker of retinopathy and nephropathy in sickle cell disease.

Purpose: This study was conducted to test the hypothesis that the carotid intima-media thickness (CIMT) is higher in patients with sickle cell disease (SCD) than in the normal population, and to determine the relationships of the CIMT with central retinal artery (CRA) and renal artery Doppler indices.

Methods: Forty-four confirmed steady-state SCD patients aged 16 years and above were recruited consecutively. The Doppler velocimetric indices of their right renal artery and both CRAs were obtained.

CYP2B6*6 Genotype Specific Differences in Artemether-Lumefantrine Disposition in Healthy Volunteers.

Cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of the antimalarial drugs artemether and lumefantrine. Here we investigated the effect of CYP2B6*6 on the plasma pharmacokinetics of artemether, lumefantrine, and their metabolites in healthy volunteers. Thirty healthy and previously genotyped adult volunteers-15 noncarriers (CYP2B6*1/*1) and 15 homozygote carriers (CYP2B6*6/*6)-selected from a cohort of 150 subjects from the Ilorin metropolitan area were administered the complete 3-day course of artemether and lumefantrine (80 and 480 mg twice daily, respectively).

The Inflammatory Response to Surgery in Sickle Cell Disease Patients Undergoing Cholecystectomy.

Background And Objectives: Patients with sickle cell anemia (SCA) may have elevated inflammatory markers in health, and this may be heightened after open operations. The inflammatory response of patients with SCA after minimally invasive surgeries has not been fully explored.

Patients And Methods: Consecutive patients with SCA and with hemoglobin AA (HbAA) undergoing laparoscopic cholecystectomy for acute cholecystitis were recruited into the study.

Doppler ultrasonographic evaluation of celiac and mesenteric arteries in subjects with sickle cell disease.

Vasculopathy, as occurring in sickle cell disease (SCD), can affect celiac and mesenteric arteries and result in stenosis, with elevated peak systolic velocity (PSV) on Doppler ultrasonography. In six subjects with confirmed SCD in steady state, routine Doppler ultrasonographic examination discovered features of celiac artery (CA) or superior mesenteric artery (SMA) stenosis with CA PSV >200 cm/s (median = 222.8 cm/s; range = 201.

Pharmacogenetics of artemether-lumefantrine influence on nevirapine disposition: Clinically significant drug-drug interaction?

Aims: In this study the influence of first-line antimalarial drug artemether-lumefantrine on the pharmacokinetics of the antiretroviral drug nevirapine was investigated in the context of selected single nucleotide polymorphisms (SNPs) in a cohort of adult HIV-infected Nigerian patients.

Methods: This was a two-period, single sequence crossover study. In stage 1, 150 HIV-infected patients receiving nevirapine-based antiretroviral regimens were enrolled and genotyped for seven SNPs.

Intima-media thickness of the common femoral artery as a marker of leg ulceration in sickle cell disease patients.

Leg ulceration is a debilitating chronic complication of sickle cell disease (SCD) the pathogenesis of which is yet to be fully elucidated. We hypothesized that SCD patients with histories of previous leg ulcers would have intima hyperplasia of the common femoral artery (CFA). We enrolled 44 SCD patients and 33 age-matched and sex-matched controls with hemoglobin AA.

Challenges to Care and Medication Adherence of Patients With Chronic Myeloid Leukemia in a Resource Limited Setting: A Qualitative Study.

The factors related to care of patients with chronic myeloid leukemia (CML) often affects treatment outcome. We examined adherence to medication and other challenges to care in our patients on treatment of CML. This qualitative study involved in-depth interviews of 20 patients with CML receiving free imatinib (Glivec) from the Glivec International Patients' Assistance Program.

Inter-individual variation in imatinib disposition: any role for prevalent variants of CYP1A2, CYP2C8, CYP2C9, and CYP3A5 in Nigerian CML patients?

Imatinib has been successful in the management of chronic myeloid leukemia (CML) but some patients experience adverse reactions or develop resistance to its use. The roles of some polymorphisms in genes encoding enzymes critical for the biotransformation of imatinib have been previously examined. This study, hence, evaluated some other unstudied functionally significant polymorphisms in CYP1A2, CYP2C8, CYP2C9, and CYP3A5.

Population Pharmacokinetics of Imatinib in Nigerians With Chronic Myeloid Leukemia: Clinical Implications for Dosing and Resistance.

Imatinib, a tyrosine kinase inhibitor, is the drug of choice for the treatment of chronic myeloid leukemia in Nigeria. Several studies have established interindividual and interpopulation variations in imatinib disposition although no pharmacokinetic study have been conducted in an African population since the introduction of the drug. This study explored a population pharmacokinetic approach to investigate the disposition of imatinib in Nigerians and examined the involvement of some covariates including genetic factors in the variability of the drug disposition with a view to optimize the use of the drug in this population.

Hepatobiliary Ultrasonographic Abnormalities in Adult Patients with Sickle Cell Anaemia in Steady State in Ile-Ife, Nigeria.

Background: Sickle cell anaemia (SCA) is associated with structural manifestations in the hepatobiliary axis. This study aimed to investigate the hepatobiliary ultrasonographic abnormalities in adult patients with sickle cell anaemia in steady state attending the Haematology clinic of a federal tertiary health institution in Ile-Ife, Nigeria.

Material/methods: Basic demographic data as well as right upper abdominal quadrant ultrasonography of 50 consecutive sickle cell anaemia patients were compared with those of 50 age- and sex-matched subjects with HbAA as controls.

Prevalence and Correlates of Peripheral Arterial Disease in Nigerians with Type 2 Diabetes.

. Peripheral arterial disease (PAD) is a major risk factor for nonhealing foot ulcers in people with diabetes. A number of traditional risk factors have been reported to be associated with PAD; however, there may be a need to consider nontraditional risk factors especially in some vulnerable populations.

Influence of CYP3A5*3 and ABCB1 C3435T on clinical outcomes and trough plasma concentrations of imatinib in Nigerians with chronic myeloid leukaemia.

What Is Known And Objective: Imatinib mesylate is the first-line drug for the treatment of Philadelphia/bcr-abl positive chronic myeloid leukaemia (CML). It is known to be metabolized mostly by CYP3A4 and CYP3A5 isoforms while its efflux is mediated by the transporters ABCB1 and ABCG2. Genetic polymorphism of some of these enzymes and transporters have been linked with inter-individual variations in the pharmacokinetics of the drug.

Chronic Myeloid Leukemia in Nigerian Patients: Anemia is an Independent Predictor of Overall Survival.

Objectives: The advent of the tyrosine kinase inhibitors has markedly changed the prognostic outlook for patients with Ph(+) and/or BCR-ABL1 (+) chronic myeloid leukemia (CML). This study was designed to assess the overall survival (OS) of Nigerian patients with CML receiving imatinib therapy and to identify the significant predictors of OS.

Methods: All patients with CML receiving imatinib from July 2003 to June 2013 were studied.