Left ventricular geometry and electrocardiographic criteria in assessing left ventricular hypertrophy in sickle cell anemia patients.

BACKGROUND: Left ventricular hypertrophy (LVH) is recognized as a cardiovascular risk factor and is a known consequence of sickle cell anemia (SCA). Abnormal left ventricular geometric patterns have been described but the determinants have not been well elucidated. METHOD: Electrocardiography (ECG) and Echocardiography (ECHO) was done on subjects with SCA and hemoglobin A(HBA). Those with systemic hypertension were excluded. Voltages, durations, and intervals were measured as appropriate and recorded in a standard proforma. Analysis was made using a standard statistical software. RESULTS: Eighty four people with SCA and 91 with HBA were recruited as cases and controls respectively. Subjects with SCA have more abnormal LV geometric patterns than those with HBA(p=0.000). Eccentric LVH(p=0.000) was more in SCA subjects while concentric LVH(p=0.054) and concentric remodeling(p=0.319) were not. Forty-one and fifty-two subjects with SCA and HBA respectively did ECGs. . Subjects with eccentric LVH had lower hip circumference, higher left atrial diameter, right atrial area, higher sokolow-lyon voltage sum, stroke volume and cardiac output. The Sokolow-Lyon voltage criteria at the traditional cut off point was not different between those with and without eccentric LVH. However, Sokolow-Lyon voltage criteria at a cut-off of ≥4.7mV detected eccentric LVH with a sensitivity of 60% and specificity of 83.3%.While Sokolow-Lyon voltage sum, stroke volume, right atrial area, and left atrial diameter correlated positively, pulse rate and hip circumference correlated inversely with eccentric LVH. Sokolow Lyon voltage sum was the independent determinant of eccentric LVH in this study. CONCLUSION: Sickle cell anemia predisposes to abnormal LV geometric patterns, especially eccentric LVH. There may be a need to review the electrocardiographic cut off points for defining eccentric LVH in the SCA populace.

Impact of relative systemic hypertension on the heart in sickle cell anaemia.

Sickle cell anaemia (SCA) is associated with macrovascular complications at relatively normal blood pressures. This has led to the development of the term 'relative systemic hypertension' (RSH). The electrocardiography (ECG) and echocardiography (ECHO) findings in these people has not been well highlighted. Patients with SCA in steady state were consecutively recruited. History, physical examination, ECG and ECHO information were obtained from all participants after informed consent was obtained. Eighty-three people were recruited in all- 15 of which had RSH, giving a prevalence of 18.1%. Those with RSH had higher packed cell volumes (PCV), smaller right atria area, lower tricuspid regurgitant velocities, lower incidence of early satiety, longer QTc and higher frequency of a history of vaso-occlusive crises. The indices of right and left ventricular function were normal in both groups. Right atrial area was the only significant determinant of RSH in this study. RSH is associated with higher PCV, longer QTc and smaller right atrial area in SCA patients. More studies to evaluate sympathetic output in SCA with RSH is required.

Sickle Cell Disease Clinical Trials and Phenotypes.

Sickle cell disease, one of the world's most common genetic disorders is prevalent in sub-Saharan Africa. The trans-Atlantic slave trade accounted for the gene movement from Africa to the Caribbean and United States of America and lately, migration has resulted in the introduction of the gene to the United Kingdom and other parts of Europe. Different haplotypes exist, however the differences in these haplotypes are not sufficient to explain the different clinical variations within the same region or different settings.

Associations of α-thalassemia and BCL11A with stroke in Nigerian, United States, and United Kingdom sickle cell anemia cohorts.

Alpha-thalassemia and the BCL11A rs1427407 T allele are commonly observed in sickle cell anemia (SCA) patients and are associated with reduced hemolysis and higher hemoglobin F levels, respectively. We investigated whether a high-risk genetic profile, defined as SCA patients who did not inherit either α-thalassemia or the BCL11A rs1427407 T allele, had stronger associations with clinical and laboratory variables than the individual genetic components in the University of Ibadan cohort (n=249). We then replicated our findings in SCA cohorts from the University of Illinois at Chicago (UIC)(n=260) and Walk-Treatment of Pulmonary Hypertension and Sickle cell disease with Sildenafil Therapy (Walk-PHaSST)(n=387). High-risk was associated with higher reticulocytes (15.0% vs. 7.8%, P=0.08) and stroke history (6% vs. 1%, P=0.02) than standard risk patients and these associations were more significant than the individual genetic components in the University of Ibadan cohort. These findings were replicated in high-risk patients from UIC and Walk-PHaSST for reticulocytes (UIC: 13.5% vs. 11.8%, P=0.03; Walk-PHaSST: 9.6% vs. 8.2%, P=0.0003) and stroke history (UIC: 32% vs. 22%, P=0.07; Walk-PHaSST: 14% vs. 7%, P=0.01). On combined analysis, high-risk had strong associations with increased markers of hemolysis (hemoglobin ß= -0.29, 95%CI: -0.50 to -0.09; P=0.006; reticulocyte% ß=2.29, 95%CI: 1.31 to 3.25; P=1x10-5) and stroke history (OR=2.0, 95%CI: 1.3 to 3.0; P=0.0002), but no association with frequent vaso-occlusive crises (≥3/year). A high-risk genetic profile is associated with increased hemolysis and stroke history in three independent cohorts. This profile may help identify patients to prioritize for hydroxyurea and for closer monitoring strategies for stroke.

Factors Associated With Waiting Time for Breast Cancer Treatment in a Teaching Hospital in Ghana.

Background Breast cancer is the leading cause of cancer-related mortality among women in Ghana. Data are limited on the predictors of poor outcomes in breast cancer patients in low-income countries; however, prolonged waiting time has been implicated. Among breast cancer patients who received treatment at Korle Bu Teaching Hospital, this study evaluated duration and factors that influenced waiting time from first presentation to start of definitive treatment. Method We conducted a hospital-based retrospective study of 205 breast cancer patients starting definitive treatment at Korle Bu Teaching Hospital between May and December 2013. We used descriptive statistics to summarize patient characteristics. Mann-Whitney U and Kruskal-Wallis tests and Spearman rank correlation were performed to examine the patients, health system, and health worker factors associated with median waiting time. Poisson regression was used to examine the determinants of waiting time. Results The mean age of the patients was 51.1 ± 11.8 years. The median waiting time was 5 weeks. The determinants of waiting time were level of education, age, income, marital status, ethnicity, disease stage, health insurance status, study sites, time interval between when biopsy was requested and when results were received and receipt of adequate information from health workers. Conclusion A prolonged waiting time to treatment occurs for breast cancer patients in Ghana, particularly for older patients, those with minimal or no education, with lower income, single patients, those with late disease, those who are insured, and who did not receive adequate information from the health workers. Time to obtain biopsy reports should be shortened. Patients and providers need education on timely treatment to improve prognosis.

Vitamin D levels are low in adult patients with sickle cell disease in Jamaica and West Africa.

BACKGROUND: Patients with sickle cell disease in the USA have been noted to have lower levels of vitamin D - measured as 25-hydroxyvitamin D (25(OH)D) - compared to controls. Average serum 25(OH)D levels are also substantially lower in African Americans than whites, while population distributions of 25(OH)D among Jamaicans of African descent and West Africans are the same as among USA whites. The purpose of this study was to examine whether adult patients with sickle cell disease living in tropical regions had reduced 25(OH)D relative to the general population. METHODS: We analyzed serum 25(OH)D in stored samples collected from studies in Jamaica and West Africa of adult patients with sickle cell disease and adult population controls. RESULTS: In samples of 20 Jamaicans and 50 West Africans with sickle cell disease mean values of 25(OH)D were 37% and 39% lower than controls, respectively. Metabolic abnormalities in the absorption and conversion pathways are possible causes for the consistent relative deficiency of 25(OH)D in sickle cell disease. CONCLUSIONS: Low 25(OH)D levels in tropical Africa where the burden of sickle cell disease is highest, deserve further investigation, and a randomized trial is warranted to address efficacy of supplementation.

Comparison of patients from Nigeria and the USA highlights modifiable risk factors for sickle cell anemia complications.

To identify factors that affect manifestations of sickle cell anemia we compared patients 11-30 years of age from University of Ibadan, Ibadan, Oyo, Nigeria (n = 214) and University of Illinois at Chicago, Chicago, IL, USA (n = 209). Paralleling findings in the general populations of the two countries, the Chicago patients were more often overweight or obese as defined by the Centers for Disease Control and Prevention (Atlanta, GA, USA) guidelines, and more often had elevated blood pressure (BP) as defined by the National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD, USA guidelines. The Ibadan patients did not receive the pneumococcal vaccine or hydroxyurea (HU) therapy as frequently as the Chicago patients. Consistent with lower rates of elevated BP and increased body mass index (BMI), stroke history was less frequent in the Ibadan patients ≥18 years old. Furthermore, in combined analyses, systolic and diastolic BP directly correlated with BMI, and elevated weight status independently associated with history of stroke. Our findings are consistent with the possibility that higher values for BMI and BP in Chicago sickle cell anemia patients may contribute to an increased risk of stroke and highlights the need for measures to reduce these risk factors. On the other hand, lower pneumococcal vaccination and HU therapy rates in Ibadan patients highlights the need for more improved vaccination coverage and for studies to define the role of HU therapy in Africa.

Level of awareness of mammography among women attending outpatient clinics in a teaching hospital in Ibadan, South-West Nigeria.

BACKGROUND: Mammography has been used in developed countries with considerable success but very little is known about this imaging modality in low resource settings. This study examined the level of awareness of mammography and determined factors influencing the level of awareness. METHODS: We conducted a hospital based cross sectional study to investigate the level of awareness of mammography among 818 randomly selected women attending the General Outpatient clinics (GOP) of the University College Hospital (UCH), Ibadan, Nigeria. Independent predictors of level of awareness of mammography were identified using multiple logistic regression analysis. RESULTS: The proportion of women who ever heard of mammography was 5%, and they demonstrated poor knowledge of the procedure. Those with primary or secondary levels of education were about three times less likely to be aware of mammography when compared with those with tertiary level of education (OR = 0.3, 95% CI, 0.12 - 0.73). Also, participation in community breast cancer prevention activities (OR = 3.4, 95% CI, 1.39 - 8.36), and previous clinical breast examination (OR = 2.34, 95% CI, 1.10 - 4.96) independently predicted mammography awareness. Newspapers and magazines appeared to be the most important sources of information about mammography screening. CONCLUSION: The level of awareness of mammography is poor among women attending outpatient clinics in the studied population. Interventions promoting awareness of this screening procedure should give particular attention to the illiterate and older women while clinicians performing breast examinations should utilize the opportunity to inform women about the mammography procedure. Promotion of educational articles on breast cancer and its screening methods via media remains vital for the literate.

Prevalence of hepatitis B and C seropositivity in a Nigerian cohort of HIV-infected patients.

INTRODUCTION: The clinical and public health implications of the convergence of the human immunodeficiency virus (HIV) epidemic and chronic viral hepatitis in sub-Saharan Africa are poorly understood. This study was designed to determine the seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV), and the impact of co-infection on baseline serum alanine transaminase (ALT), CD4+ T lymphocyte (CD4) count, and plasma HIV-RNA (viral load) in a cohort of HIV-infected Nigerians. METHODS: A retrospective study was conducted, on eligible treatment-naive patients who presented between August 2004 and February 2007 to the University College Hospital (UCH), Ibadan, Nigeria. Demographic data and pre-treatment laboratory results (hepatitis B surface antigen (HBsAg), HCV antibodies (anti-HCV), ALT, CD4 count and viral load) were retrieved from the medical records. Fisher's exact, two sample t-tests, and the Wilcoxon rank sum tests were used to compare groups. A logistic regression model was fitted to explore characteristics associated with co-infection status. RESULTS: A total of 1779 HIV-infected patients (male: female ratio, 1:2) met inclusion criteria. HBsAg was present in 11.9%, anti-HCV in 4.8% and both markers in 1%. HBsAg was more common among males than females (15.4% vs 10.1%, respectively p = 0.001) while anti-HCV was detected in a similar proportion of males and females (5.3% versus 4.6%, respectively p = 0.559). HIV-infected patients with anti-HCV alone had a lower mean baseline CD4 count compared to those without anti-HCV or HBsAg (197 cells/mm3 vs 247 cells/mm3, respectively p = 0.008). Serum ALT was higher among patients with HBsAg compared to those without HBsAg or anti-HCV (43 International Units (IU) vs. 39 IU, respectively p = 0.015). Male gender was associated with HBV co-infection on logistic regression (OR1.786; 95% CI, 1.306-2.443; p < 0.005). CONCLUSION: More HIV-infected females than males presented for care in this cohort. We identified a relatively high prevalence of HBV and HCV co-infection in general, and a higher rate of HBV co-infection among males than females. Pre-treatment CD4 count was significantly lower among those with HCV co-infection, while ALT was slightly higher among those with HBV co-infection. Triple infection with HIV, HBV and HCV was present in a small but significant proportion of patients. These findings underscore the importance of testing for HBV and HCV in all HIV-infected persons in our setting.

Varying apparent rate constant: determination of uptake and release of protons during tetramer-dimer dissociation in human hemoglobin A.

The effect of association-dissociation on the sulphydryl reactivity of human hemoglobin A is reported. The reactivity of CysF9(93)beta towards the sulphydryl reagent, 5,5'-dithiobis(2-nitrobenzoate), is higher at lower concentrations of hemoglobin at all pH values. This is because hemoglobin dimers have higher sulphydryl reactivity than tetramers and it is known that the proportion of dimers increases as the hemoglobin concentration decreases. This study takes advantage of this observation to determine the tetramer-dimer dissociation constant, K(4,2), of hemoglobin A and subsequently the proton uptake and the proton release during this process. The concentration dependence profiles of the apparent second-order rate constants, k(app), show that (between 2 and 20 microM heme) k(app) decreases with increasing hemoglobin concentration. Above 30 M heme k(app) remains fairly constant for all hemoglobin derivatives (oxy, carbonmonoxy and aquomethemoglobin) used. The pH dependence of the negative logarithm of tetramer-dimer dissociation constant, pK(4,2), for oxy- (and for carbonmonoxy-) hemoglobin exhibits a biphasic character with a maximum near pH 7.4 (and 6.6). For aquomethemoglobin, pK(4,20 decreases with increasing pH. The tetramer-dimer dissociation of human oxyhemoglobin A at an ionic strength of 200 mM uptakes 0.87 +/- 0.09 mole of protons between pH 6.2 to 7.4 phase and releases 0.84 0.09 mole of protons between pH 7.4 and 9.0 phase. Under a similar condition carbonmonoxyhemoglobin uptakes 0.54 +/- 0.05 mole of protons between pH 5.8 and 6.6 phase and releases 0.48 +/- 0.05 mole of protons between pH 6.6 and 9.0 phase. Aquomethemoglobin has only a single phase, it releases 0.39 +/- 0.05 mole of protons during tetramer-dimer dissociation.