Non-compartmental and population pharmacokinetic analysis of dapsone in healthy NIGERIANS: A pilot study.

Dapsone is employed for both non-dermatological and dermatological indications but with non-existent population pharmacokinetics (popPK) data in Nigerians. This study was therefore designed to develop a popPK model in Nigerians. Non-compartmental analysis and nonlinear mixed effects modelling were utilized for data analysis.

Structure-based computational design of novel covalent binders for the treatment of sickle cell disease.

The quest in finding an everlasting panacea to the pernicious impact of sickle cell disease (SCD) in the society hit a turn of success since the recent discovery of a small molecule reversible covalent inhibitor, Voxelotor. A drug that primarily promotes the stability of oxygenated hemoglobin and inhibit the polymerization of HbS by enhancing hemoglobin's affinity for oxygen has opened a new frontier in drug discovery and development. Despite eminent efforts made to reproduce small molecules with better therapeutic targets, none has been successful.

The Effect of Alpha Thalassemia, HbF and HbC on Haematological Parameters of Sickle Cell Disease Patients in Ibadan, Nigeria.

Background: Sickle cell disease is a protean disease with limited data on Nigeria's phenotypic and genetic variants. This study was conducted to provide baseline data on these variants by characterising the existing forms of sickle cell disease and correlating these with basic haematological parameters.

Methods: Adult and paediatric patients with SCD were recruited from a tertiary health centre in Nigeria.

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium.

Diagnostic Accuracy of HemotypeSC as a Point-of-Care Testing Device for Sickle Cell Disease: Findings from a Southwestern State in Nigeria and Implications for Patient Care in Resource-Poor Settings of sub-Saharan Africa.

This study aimed to determine the performance of a rapid, point-of-care testing device (HemotypeSC)™ for diagnosing sickle cell disease (SCD) relative to 2 commonly-used methods compared to DNA polymerase chain reaction (PCR) as the reference standard. The diagnostic performance of (HemotypeSC)™ in diagnosing SCD and determining various other Hb genotypes relative to high performance liquid chromatography (HPLC) and cellulose acetate Hb electrophoresis in alkaline buffer (CAE) was investigated among 156 participants aged 4 to 23 years in Ekiti, Southwest Nigeria. PCR was considered as the reference method/gold standard.

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC).

Haematological indices of sickle cell patients with chronic leg ulcers on compression therapy.

Background: Recurrent chronic leg ulcers and its are morbidities associated with sickle cell anaemia (SCA). Compression therapy increases the rate of healing of these ulcers and also decreases the rate of recurrence.

Objective: This study evaluated the haematological parameters of patients with SCA and chronic leg ulcers placed on high compression bandaging to provide data for improved ulcer management and prevention.

N-acetyltransferase 2 enzyme genotype-phenotype discordances in both HIV-negative and HIV-positive Nigerians.

Background: The N-acetyltransferase 2 (NAT2) enzyme has been understudied in Nigerians including genotype-phenotype association studies.

Objective: The aim of this study was NAT2 haplotype identification and genotype-phenotype investigations in HIV-positive and HIV-negative Nigerians.

Patients And Methods: Phenotypes included self-reported sulphonamide hypersensitivity survey, experimental and computational NAT2 phenotyping.

Author Correction: Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features.

The original version of this Article contained an error in the author affiliations. The affiliation of Kevin P. White with Tempus Labs, Inc.

Inherited Breast Cancer in Nigerian Women.

Purpose: Among Nigerian women, breast cancer is diagnosed at later stages, is more frequently triple-negative disease, and is far more frequently fatal than in Europe or the United States. We evaluated the contribution of an inherited predisposition to breast cancer in this population.

Patients And Methods: Cases were 1,136 women with invasive breast cancer (mean age at diagnosis, 47.

Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry.

Genome-wide association studies have identified approximately 100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Because of different patterns of linkage disequilibrium, many of these genetic markers may not represent signals in populations of African ancestry. We tested 74 breast cancer risk variants and conducted fine-mapping of these susceptibility regions in 6,522 breast cancer cases and 7,643 controls of African ancestry from three genetic consortia (AABC, AMBER, and ROOT).

Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer.

Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina’s HumanOmni2.

Phenotyping and genotyping of CYP2C19 using comparative metabolism of proguanil in sickle-cell disease patients and healthy controls in Nigeria.

Polymorphic expression of metabolic enzymes have been identified as one of the key factors responsible for the interindividual/ethnic/racial variability in drug metabolism and effect. In Nigeria, there is a disproportionately high incidence of sickle-cell disease (SCD), a condition characterized by painful crisis frequently triggered by malaria. Proguanil, a substrate of the polymorphic CYP2C19, is a chemoprophylactic antimalarial drug widely used among SCD patients in Nigeria.

Significant Pharmacokinetic Interactions Between Quinine and Ampicillin-Cloxacillin Combination.

Introduction: The co-existence of malaria with bacterial infections is common in the tropics, hence the concurrent use of antimalarials and antibiotics.

Objective: This study aimed to investigate the effect on pharmacokinetics and antimicrobial activity of co-administration of quinine and combined ampicillin-cloxacillin.

Methods: In total, 14 healthy adults received single oral doses of ampicillin-cloxacillin combination alone and with quinine in a randomized crossover manner.

Use of Web-based training for quality improvement between a field immunohistochemistry laboratory in Nigeria and its United States-based partner institution.

The importance of hormone receptor status in assigning treatment and the potential use of human epidermal growth factor receptor 2 (HER2)-targeted therapy have made it beneficial for laboratories to improve detection techniques. Because interlaboratory variability in immunohistochemistry (IHC) tests may also affect studies of breast cancer subtypes in different countries, we undertook a Web-based quality improvement training and a comparative study of accuracy of immunohistochemical tests of breast cancer biomarkers between a well-established laboratory in the United States (University of Chicago) and a field laboratory in Ibadan, Nigeria. Two hundred and thirty-two breast tumor blocks were evaluated for estrogen receptors (ERs), progesterone receptors (PRs), and HER2 status at both laboratories using tissue microarray technique.

Neo-adjuvant capecitabine chemotherapy in women with newly diagnosed locally advanced breast cancer in a resource-poor setting (Nigeria): efficacy and safety in a phase II feasibility study.

The majority of clinical trials of neo-adjuvant therapy for breast cancer have been conducted in resource-rich countries. We chose Nigeria, a resource-poor country, as the major site for a phase II feasibility open-label multicenter clinical trial designed to evaluate the efficacy, safety, and tolerability of neo-adjuvant capecitabine in locally advanced breast cancer (LABC). Planned treatment consisted of 24 weeks of capecitabine at a dose of 1,000 mg/m(2) twice daily (2,000 mg/m(2) total per day).

Fine mapping of breast cancer genome-wide association studies loci in women of African ancestry identifies novel susceptibility markers.

Numerous single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified by genome-wide association studies (GWAS). However, these SNPs were primarily discovered and validated in women of European and Asian ancestry. Because linkage disequilibrium is ancestry-dependent and heterogeneous among racial/ethnic populations, we evaluated common genetic variants at 22 GWAS-identified breast cancer susceptibility loci in a pooled sample of 1502 breast cancer cases and 1378 controls of African ancestry.

High prevalence of BRCA1 and BRCA2 mutations in unselected Nigerian breast cancer patients.

Inherited mutations in the BRCA1 and BRCA2 genes are the strongest genetic predictors of breast cancer and are the primary causes of familial breast/ovarian cancer syndrome. The frequency, spectrum and penetrance of mutant BRCA1/BRCA2 alleles have been determined for several populations, but little information is available for populations of African ancestry, who suffer a disproportionate burden of early onset breast cancer. We have performed complete sequence analysis of all BRCA1 and BRCA2 exons and intron-exon boundaries for 434 Nigerian breast cancer patients from the University College Hospital in Ibadan, Nigeria.

Establishment of a standing ethics/institutional review board in a nigerian university: a blueprint for developing countries.

AN ETHICS/INSTITUTIONAL REVIEW BOARD (IRB) was established according to International standards at the University of Ibadan in Nigeria. To achieve this, a private-public partnership was developed to support a review of prevailing practice and the development of necessary infrastructure for an effective IRB. An internationally registered and well-constituted IRB with a federal-wide assurance (FWA) from the National Institute of Health in the United States was established within a year.