Assessment of Right Ventricular Systolic Function using Tricuspid Annular Plane Systolic Excursion (TAPSE) among HIV Patients on HAART and Its Relationship with Viral Load and CD4 Cell Count.

BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) has decreased the morbidity and mortality associated with HIV infection; however, this survival advantage is not free from complications. HIV patients are more likely to develop cardiovascular disease compared with the general population, and right ventricular systolic dysfunction is said to be associated with worse outcomes. We, therefore, sought to assess right ventricular systolic function using tricuspid annular plain systolic excursion (TAPSE) among HIV patients on HAART and its relationship with viral load and CD4 cell count. METHODS: The study was a cross-sectional conducted among HIV patients receiving HAART at the Federal Medical Centre, Nguru, Yobe State, Northeastern Nigeria. Right ventricular systolic function was assessed using tricuspid annular plane systolic excursion. RESULTS: One hundred and seven (107) subjects were recruited into the study comprising thirty-seven (34.6%) males and seventy (65.4%) females. The mean CD4 cell count and viral load of the studied patients were 612.65 ± 347.62 cells/µL and 315.44±271.11copies/mL, respectively. The distribution of RVSF according to CD4 cell count showed, fifteen (14.01%) patients with CD4 cell count less than 250 had reduced right ventricular systolic function (RVSF), 30 (28.03%) patients with CD4 cell count 250 - 500 had reduced RVSF, 1 (0.93%) patient with CD4 cell count 250 - 500 had normal RVSF, 47 (43.92%) patients with CD4 cell count 501 -1,000 had normal RVSF and 14(13.08%) patients with CD4 cell count greater than 1,000 had normal RVSF. Fourteen (13.08%) patients with undetectable viral load had normal RVSF, 47(43.92%) patients with viral load 50 - 1,500 had normal RVSF, 1(0.93%) patient with viral load 1,501 - 10,000 had normal RVSF, 30(28.03%) patients with viral load 1,501 - 10,000 had reduced RVSF and 15(14.01%) patients with viral load 10,000 - 50,000 had reduced RVSF. There was a positive and significant correlation between tricuspid annular plain systolic excursion with CD4 cell count and a negative but significant correlation HIV viral load. CONCLUSION: We therefore concluded that asymptomatic right ventricular systolic dysfunction exists among patients with HIV infection and there was positive and significant correlation between tricuspid annular plain systolic excursion with CD4 cells count and a negative but significant correlation HIV viral load.

CONTEXTE: L'introduction du traitement antirétroviral hautement actif (HAART) a réduit la morbidité et la mortalité associées à l'infection par le VIH; cependant, cet avantage de survie n'est pas exempt de complications. Les patients VIH ont plus de risques de développer des maladies cardiovasculaires par rapport à la population générale, et une dysfonction systolique ventriculaire droite est dite être associée à des résultats plus graves. Nous avons donc cherché à évaluer la fonction systolique ventriculaire droite à l'aide de l'excursion systolique du plan annulaire tricuspidien (TAPSE) chez les patients VIH sous HAART et sa relation avec la charge virale et le taux de lymphocytes CD4. MÉTHODES: L'étude était une étude transversale menée auprès de patients VIH recevant le HAART au Federal Medical Centre, Nguru, État de Yobe, dans le nord-est du Nigéria. La fonction systolique ventriculaire droite a été évaluée à l'aide de l'excursion systolique du plan annulaire tricuspidien. RÉSULTATS: Cent sept (107) sujets ont été recrutés dans l'étude, dont trente-sept (34,6%) hommes et soixante-dix (65,4%) femmes. Le taux moyen de lymphocytes CD4 et la charge virale des patients étudiés étaient respectivement de 612,65 ± 347,62 cellules/µL et 315,44 ± 271,11 copies/mL. La répartition de la fonction systolique ventriculaire droite selon le taux de lymphocytes CD4 a montré que quinze (14,01%) patients ayant un taux de lymphocytes CD4 inférieur à 250 présentaient une fonction systolique ventriculaire droite réduite, 30 (28,03%) patients ayant un taux de lymphocytes CD4 de 250 à 500 avaient une fonction systolique ventriculaire droite réduite, 1 (0,93%) patient ayant un taux de lymphocytes CD4 de 250 à 500 avait une fonction systolique ventriculaire droite normale, 47 (43,92%) patients ayant un taux de lymphocytes CD4 de 501 à 1 000 avaient une fonction systolique ventriculaire droite normale et 14 (13,08%) patients ayant un taux de lymphocytes CD4 supérieur à 1 000 avaient une fonction systolique ventriculaire droite normale. Quatorze (13,08%) patients avec une charge virale indétectable avaient une fonction systolique ventriculaire droite normale, 47 (43,92%) patients avec une charge virale de 50 à 1 500 avaient une fonction systolique ventriculaire droite normale, 1 (0,93%) patient avec une charge virale de 1 501 à 10 000 avait une fonction systolique ventriculaire droite normale, 30 (28,03%) patients avec une charge virale de 1 501 à 10 000 avaient une fonction systolique ventriculaire droite réduite et 15 (14,01%) patients avec une charge virale de 10 000 à 50 000 avaient une fonction systolique ventriculaire droite réduite. Il y avait une corrélation positive et significative entre l'excursion systolique du plan annulaire tricuspidien et le taux de lymphocytes CD4 et une corrélation négative mais significative avec la charge virale du VIH. CONCLUSION: Nous concluons donc qu'une dysfonction systolique ventriculaire droite asymptomatique existe chez les patients atteints d'une infection par le VIH et qu'il existe une corrélation positive et significative entre l'excursion systolique du plan annulaire tricuspidien et le taux de lymphocytes CD4, ainsi qu'une corrélation négative mais significative avec la charge virale du VIH. MOTS CLÉS: Fonction Systolique Ventriculaire Droite, Excursion Systolique du Plan Annulaire Tricuspidien (TAPSE), CD4, Charge Virale, VIH.

Prevalence of Doppler-Derived Left Ventricular Diastolic Dysfunction Among Newly Diagnosed Hypertensive Patients.

BACKGROUND: The initial sign of hypertensive heart disease (HHD) is left ventricular diastolic dysfunction (LVDD), which is caused by remodeling of the left ventricle and left atrium, resulting in impaired relaxation of the left ventricle. LVDD is also partly due to left ventricular hypertrophy (LVH). If left untreated, LVDD can progress to diastolic heart failure and systolic heart failure. In Western countries, the prevalence of LVDD in long-term hypertensive patients ranges from 40.3% to 60%, but it is more common among hypertensive Nigerians. Since systemic hypertension can be asymptomatic in the early stages, it is important to evaluate LVDD early and control blood pressure to slow down its progression. AIMS AND OBJECTIVES: The study aims to highlight the prevalence of LVDD and to determine the stages of LVDD among newly diagnosed hypertensive patients at the University of Maiduguri Teaching Hospital (UMTH). METHOD: The study design is a hospital-based, cross-sectional, observational study. The study population consists of 352 consecutive treatment Naïve hypertensive adult patients aged 18 years and above who presented to the Cardiology Clinic of UMTH from June 2019 to June 2021. The study used the diagnostic criteria for LVDD and LVH which were based on the American Society of Echocardiography and the European Association of Cardiovascular Imaging. RESULTS: A total of 352 newly diagnosed hypertensive patients were recruited, with a mean age of 50.9 ± 11.8 years, and 54.3% were female. The majority of patients (63.6%) were overweight or obese, with a mean body mass index (BMI) of 28.5 ± 4.6 kg/m2. The mean systolic blood pressure (SBP) was 155.7 ± 16.9 mmHg, and the mean diastolic blood pressure (DBP) was 92.8 ± 10.8 mmHg. LVDD was found in 58.5% of the patients, with stage 1 LVDD being the most common (42.6%), followed by stage 2 LVDD (15.9%). The prevalence of LVDD was significantly higher in females compared to males. Patients with LVDD were significantly older and had higher BMI, higher systolic and DBP, higher pulse pressure, higher LAVI, and higher LVMI compared to those without LVDD (P < 0.05). CONCLUSION: LVDD is highly prevalent among newly diagnosed hypertensive patients, with stage 1 being the most common. Female gender, older age, higher BMI, higher blood pressure, higher LAVI, and higher LVMI were significant predictors of LVDD. Early detection and appropriate management of LVDD may help to prevent adverse cardiovascular outcomes in hypertensive patients.

Echocardiographic Left Ventricular Hypertrophy and Geometric Patterns in Patients with Sickle Cell Anaemia.

BACKGROUND: Left ventricular hypertrophy (LVH) is a common complication in patients with sickle cell anaemia (SCA), and it has been associated with systolic and diastolic dysfunction, and sudden death. There is a wide variation in the reported prevalence of LVH in patients with SCA, partly due to the varying criteria applied, and the impact of small weight and body surface area (BSA) in SCA patients. We used four different criteria to determine echocardiographic LVH and geometric patterns in patients with steady-state SCA. Left ventricular hypertrophy was defined by LVM, LVM indexed to BSA, LVM indexed to height and LVM indexed to height2.7 using gender-specific reference values. Left ventricular geometry was determined using LVH and relative wall thickness. RESULTS: Eighty-two patients with steady-state SCA, aged 18years and above were studied from January 2018 to April 2018. The median [IQR] age of the patients was 23 [10] years. Forty-seven (57.3%) were females. The prevalence of LVH was highest when LVM was indexed to BSA (80.5%), followed by LVM indexed to height (73.2%). Comparable prevalences of 68.3% and 69.5% were observed using LVM and LVM indexed to height2.7, respectively. The prevalence of LVH was similar in males and females for all the criteria. CONCLUSION: The prevalence of LVH is high among patients with steady-state SCA irrespective of the criteria applied. The most prevalent geometric pattern was eccentric LVH. Indexing to BSA might result in over-estimation of LVH given the relatively small BSA in patients with SCA. Indexing to height 2.7 might give a more accurate estimate of LVH.

CONTEXTE: L'hypertrophie ventriculaire gauche (HVG) est une complication fréquente chez les patients atteints d'anémie falciforme (ACS), et elle a été associée à un dysfonctionnement systolique et diastolique, ainsi qu'à une mort subite. La prévalence de l'HVG chez les patients atteints d'anémie falciforme varie considérablement, en partie à cause des différents critères appliqués et de l'impact du petit poids et de la surface corporelle (BSA) des patients atteints d'anémie falciforme. Nous avons utilisé quatre critères différents pour déterminer l'HVG échocardiographique et les schémas géométriques chez les patients atteints d'ACS à l'état stable. L'hypertrophie ventriculaire gauche a été définie par la MVL, la MVL indexée sur la surface corporelle, la MVL indexée sur la taille et la MVL indexée sur la taille2,7 en utilisant des valeurs de référence spécifiques au sexe. La géométrie du ventricule gauche a été déterminée en utilisant l'HVG et l'épaisseur relative de la paroi. RÉSULTATS: Quatre-vingts deux patients atteints d'ACS à l'état stable, âgés de 18 ans et plus ont été étudiés de janvier 2018 à avril 2018. L'âge médian [IQR] des patients était de 23 [10] ans. Quarantesept (57,3 %) étaient des femmes. La prévalence de l'HVG était la plus élevée lorsque la MVL était indexée sur la BSA (80,5 %), suivie de la MVL indexée sur la taille (73,2 %). Une prévalence comparable de 68,3 % et 69,5 % a été observée en utilisant la MVL et la MVL indexée sur la taille2,7, respectivement. La prévalence de l'HVG est similaire chez les hommes et les femmes pour tous les critères. CONCLUSION: La prévalence de l'HVG est élevée chez les patients atteints d'ACS à l'état stable, quel que soit le critère appliqué. Le modèle géométrique le plus répandu est l'HVG excentrique. L'indexation à la BSA pourrait entraîner une surestimation de l'HVG étant donné la BSA relativement faible chez les patients atteints d'ACS. L'indexation à la taille 2,7 pourrait donner une estimation plus précise de l'HVG. Mots clés: Hypertrophie ventriculaire gauche; Géométrie ventriculaire gauche; Drépanocytose ; Échocardiographie.

Influence of systolic blood pressure on outcomes in Nigerians with peripartum cardiomyopathy.

Background: The relationship between blood pressure (BP) trajectories and outcomes in patients with peripartum cardiomyopathy (PPCM) is not clear. Aim: The study aimed to assess the clinical features and outcomes (all-cause mortality and unrecovered left ventricular [LV] systolic function) of PPCM patients grouped according to their baseline systolic BP (SBP). Patients and Methods: PPCM patients presenting to 14 tertiary hospitals in Nigeria were consecutively recruited between June 2017 and March 2018 and then followed up till March 2019. SBP at first presentation was used to categorize the patients into seven groups: <90, 90-99, 100-109, 110-119, 120-129, 130-139, and ≥140 mmHg. Unrecovered LV systolic function was defined as echocardiographic LV ejection fraction (LVEF) below 55% at the last profiling. Results: Two hundred and twenty-seven patients were recruited and followed up for a median of 18 months. Of these, 4.0% had <90 mmHg, 16.3% had 90-99 mmHg, 24.7% had 100-109 mmHg, 24.7% had 110-119 mmHg, 18.5% had 120-129 mmHg, 7.5% had 130-139 mmHg, and 4.4% had ≥140 mmHg of SBP at presentation. The highest frequency of all-cause mortality was recorded among patients with SBP ≤90 mmHg (30.8%) followed by those with 90-99 mmHg (20.5%) (P = 0.076), while unrecovered LV systolic function did not differ significantly between the groups (P = 0.659). In a Cox proportional regression model for all-cause mortality, SBP <90 mmHg had a hazard ratio (HR) of 4.00 (95% confidence interval [CI] 1.49-10.78, P = 0.006), LVEF had an HR of 0.94 (95% CI 0.91-0.98, P = 0.003, B = 0.06%), and use of angiotensin-converting enzyme or angiotensin receptor and/or ß-receptor blockers had an HR of 1.71 (95% CI 0.93-3.16, P = 0.085). However, SBP was not associated with LV function recovery. Conclusion: In our cohort of PPCM patients, one-fifth was hypotensive at presentation. SBP <90 mmHg at presentation was associated with a four-fold higher risk of all-cause mortality during a median follow-up of 18 months.

Impact of Climate Change on Management of Systemic Hypertension in North-Eastern Nigeria.

The impact of climate change on health, including changes in epidemiology and heat-related complications, has been variously reported in many parts of the world. Maiduguri, the capital of Borno state in north-eastern Nigeria, has been bearing the brunt of increasing temperatures over the past years, especially during the early months of the year building up to the commencement of the rainy season; with an average daily temperature forecasted to be around 40C. Patients with systemic hypertension and other forms of cardiovascular diseases are vulnerable to heat-related complications including dehydration, hypotension, and orthostatic hypotension (OH). This is particularly true in patients receiving various forms of antihypertensive medication, including diuretics. We present three cases of symptomatic OH occurring during the peak of heat season in Maiduguri among patients receiving various combinations of antihypertensive medication.L'impact du changement climatique sur la santé, y compris les changements dans l'épidémiologie et les complications liées à la chaleur, a été diversement rapporté dans de nombreuses régions du monde. Maiduguri, la capitale de l'État de Borno, dans le nord-est du Nigeria, a subi de plein fouet l'augmentation des températures au cours des dernières années, en particulier au cours des premiers mois de l'année, jusqu'au début de la saison des pluies. Les patients souffrant d'hypertension systémique et d'autres formes de maladies cardiovasculaires sont vulnérables aux complications liées à la chaleur, notamment la déshydratation, l'hypotension et l'hypotension orthostatique (OH). Cela est particulièrement vrai chez les patients recevant diverses formes de médicaments antihypertenseurs, notamment des diurétiques. Nous présentons trois cas d'OH symptomatique survenus pendant le pic de la saison chaude à Maiduguri chez des patients recevant diverses combinaisons de médicaments antihypertenseurs. Mots clés: Changement climatique, Hypertension, Agents antihypertenseurs, Hypotension orthostatique, Zone semiaride, Maiduguri, Nigeria.

Relationship between CD4 Cell Count, Viral Load and Left Ventricular Function among HIV-1 Infected Patients Asymptomatic for Cardiac Disease on HAART.

INTRODUCTION: Human immunodeficiency virus (HIV) infected patients are at increased risk for myocardial infarction and cardiomyopathy. Low CD4 cell count and high viral load were identified as independent risk factors for cardiac disease. Asymptomatic cardiac dysfunction has also been reported in HIV-infected individuals. METHODS: This was a cross-sectional study conducted among consecutive HIV patients who are asymptomatic for cardiac disease receiving highly active antiretroviral therapy (HAART) at the ART clinic of Federal Medical Centre Nguru, Yobe State Northeastern Nigeria. DATA ANALYSIS: Statistical analysis was done using SPSS version 21.0 (SPSS IBM) Chicago Illinois. Data were presented as mean ± standard deviation (SD) for continuous variables, while categorical variables were expressed as frequencies and proportions. Correlation and regression analyses were done to determine the relationship between CD4 cell count, viral load and left ventricular function. A p-value of d"0.05 was considered significant. RESULTS: Patients with high CD4 cells count (>500 cells/µL) were found to have preserved left ventricular systolic function while those with low CD4 cells count (500 cells/µL while those with low CD4 cell count (1500 copies/mL) were associated with reduced left ventricular systolic function and severe diastolic dysfunction. We therefore suggest that there is need for early evaluation of left ventricular function in HIV patients before developing symptoms of cardiac decompensation.

RÉSUMÉ: Les patients infectés par le virus de l'immunodéficience humaine (VIH) présentent un risque accru d'infarctus du myocarde et de cardiomyopathie. Un faible nombre de cellules CD4 et une charge virale élevée ont été identifiés comme des facteurs de risque indépendants de maladie cardiaque. Un dysfonctionnement cardiaque asymptomatique a également été rapporté chez des personnes infectées par le VIH. MÉTHODES: Il s'agissait d'une étude transversale menée auprès de patients VIH consécutifs asymptomatiques de maladie cardiaque recevant un traitement antirétroviral hautement actif (HAART) à la clinique ART du Federal Medical Center Nguru, dans l'État de Yobe, au nord-est du Nigéria. ANALYSE DES DONNÉES: L'analyse statistique a été effectuée à l'aide de SPSS version 21.0 (SPSS IBM) Chicago Illinois. Les données ont été présentées sous forme de moyenne ± écart-type (SD) pour les variables continues, tandis que les variables catégorielles ont été exprimées sous forme de fréquences et de proportions. Des analyses de corrélation et de régression ont été effectuées pour déterminer la relation entre le nombre de cellules CD4, la charge virale et la fonction ventriculaire gauche. Une valeur p de d"0,05 a été considérée comme significative. RÉSULTATS: Les patients avec un nombre élevé de cellules CD4 (> 500 cellules/µL) ont conservé la fonction systolique ventriculaire gauche tandis que ceux ayant un faible nombre de cellules CD4 (500 cellules/µL tandis que ceux ayant un faible nombre de cellules CD4 (1500 copies/mL) étaient associée à une fonction systolique ventriculaire gauche réduite et à un dysfonctionnement diastolique sévère. Nous suggérons donc qu'il est nécessaire d'évaluer précocement la fonction ventriculaire gauche chez les patients VIH avant de développer des symptômes de décompensation cardiaque. MOTS CLÉS: VIH, fonction ventriculaire gauche, numération des CD4 et charge virale.

Incidence, clinical characteristics, and risk factors of peripartum cardiomyopathy in Nigeria: results from the PEACE Registry.

AIMS: The aim of this study was to describe the incidence, clinical characteristics and risk factors of peripartum cardiomyopathy (PPCM) in Nigeria. METHODS AND RESULTS: The study was conducted in 22 hospitals in Nigeria, and PPCM patients were consecutively recruited between June 2017 and March 2018. To determine factors associated with PPCM, the patients were compared with apparently healthy women who recently delivered, as controls. Four hundred six patients were compared with 99 controls. The incidence and disease burden (based on the rate of consecutive recruitment of subjects) varied widely between the six geographical zones of Nigeria. From the North-West zone, 72.3% of the patients was recruited, where an incidence as high as 1 per 96 live births was obtained in a centre, while the disease was uncommon (7.6% of all recruited patients) in the South. Majority of the patients (76.6%) and controls (74.8%) (p = 0.694) were of Hausa-Fulani ethnic group. Atrial fibrillation, intracardiac thrombus, stroke, and right ventricular systolic dysfunction were found in 1.7%, 6.4%, 2.2%, and 54.9% of the patients, respectively. Lack of formal education (odds ratio [OR] 3.08, 95% confidence interval [1.71, 5.53]; P < 0.001), unemployment (OR: 3.28 [2.05, 5.24]; P < 0.001), underweight (OR: 13.43 [4.17, 43.21]; P < 0.001) and history of pre-eclampsia (OR: 9.01 [2.18, 37.75]; P = 0.002) emerged as independent PPCM risk factors using regression models. Customary hot baths (OR: 1.24 [0.80, 1.93]; P = 0.344), pap enriched with dried lake salt (OR: 1.20 [0.74, 1.94]; P = 0.451), and Hausa-Fulani ethnicity (OR: 1.11 [0.67, 1.84]; P = 0.698) did not achieve significance as PPCM risk factors. CONCLUSIONS: In Nigeria, the burden of PPCM was greatest in the North-West zone, which has the highest known incidence. PPCM was predicted by sociodemographic factors and pre-eclampsia, which should be considered in its control at population level. Postpartum customary birth practices and Hausa-Fulani ethnicity were not associated with PPCM in Nigeria.

Status of cardiac arrhythmia services in Africa in 2018: a PASCAR Sudden Cardiac Death Task Force report.

BACKGROUND: There is limited information on the availability of health services to treat cardiac arrhythmias in Africa. METHODS: The Pan-African Society of Cardiology (PASCAR) Sudden Cardiac Death Task Force conducted a survey of the burden of cardiac arrhythmias and related services over two months (15 October to 15 December) in 2017. An electronic questionnaire was completed by general cardiologists and electrophysiologists working in African countries. The questionnaire focused on availability of human resources, diagnostic tools and treatment modalities in each country. RESULTS: We received responses from physicians in 33 out of 55 (60%) African countries. Limited use of basic cardiovascular drugs such as anti-arrhythmics and anticoagulants prevails. Non-vitamin K-dependent oral anticoagulants (NOACs) are not widely used on the continent, even in North Africa. Six (18%) of the sub-Saharan African (SSA) countries do not have a registered cardiologist and about one-third do not have pacemaker services. The median pacemaker implantation rate was 2.66 per million population per country, which is 200-fold lower than in Europe. The density of pacemaker facilities and operators in Africa is quite low, with a median of 0.14 (0.03-6.36) centres and 0.10 (0.05-9.49) operators per million population. Less than half of the African countries have a functional catheter laboratory with only South Africa providing the full complement of services for cardiac arrhythmia in SSA. Overall, countries in North Africa have better coverage, leaving more than 110 million people in SSA without access to effective basic treatment for cardiac conduction disturbances. CONCLUSION: The lack of diagnostic and treatment services for cardiac arrhythmias is a common scenario in the majority of SSA countries, resulting in sub-optimal care and a subsequent high burden of premature cardiac death. There is a need to improve the standard of care by providing essential services such as cardiac pacemaker implantation.

Prevalence of overweight and obesity in Maiduguri, North-Eastern Nigeria.

BACKGROUND: The prevalence of obesity is on the increase worldwide including in many developing countries. There is no report on the magnitude of obesity among adults in Maiduguri, a major city in northeastern Nigeria. MATERIALS AND METHODS: We selected a sample of 1650 men and women aged 15 years and above resident in Gwange ward in Maiduguri metropolitan council using a multistage sampling technique. Height, weight, waist (WC) and hip circumferences w measured. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated. Data were analyzed using SPSS version13. The ethics committee of the University of Maiduguri Teaching Hospital approved the study and consent was sought individually from the participants before being enlisted. RESULTS: The mean (SD) age of the respondents was 36.2 (14.4) years, with a range of 15 to 70 years. The mean (SD) ages of the males and females were 34.9 4.3) and 38.9 (14.0) years, respectively, (p < 0.001). The overall crude prevalence rates of overweight and obesity were 27.1% and 17.1%, respectively. In men, 40.6% were either overweight or obese, while in women 51.9% were either overweight or obese. We observed the highest prevalence rates of overweight and obesity in the middle age group. There were more obese females than males (14.05 vs. 4.3%) among both young and elderly (12.1% vs. 10.5%) subjects. CONCLUSION: The prevalence of overweight and obesity is high in Maiduguri metropolis particularly among women. Concerted efforts should be made to curb the menace of increasing rate of obesity in the metropolis through public enlightenment on the risks associated with obesity and the benefits of adopting a healthy lifestyle.

Left ventricular geometry in Nigerians with type II diabetes mellitus.

BACKGROUND: Left ventricular hypertrophy is independently associated with increased incidence of cardiovascular disease, cardiovascular and all cause mortality. In a relatively healthy hypertensive adult population, type II diabetes is associated with higher left ventricular mass, concentric left ventricular geometry and lower myocardial function independent of age, sex, body size, and arterial blood pressure. OBJECTIVE: The study is to investigate left ventricular geometry in Nigerians with Type II Diabetes mellitus. METHODS: The study design was cross-sectional and it comprised 75 consecutive patients with type II diabetes mellitus with or without hypertension. Using a structured pre-evaluated questionnaire, the demographic and clinical data were obtained. All subjects had two dimensional (2D) and 2D derived M-mode echocardiography using Sonoline G60s Ultrasound imaging system with 4.2 MHZ transducer equipped with simultaneous ECG tracing. RESULTS: A total of 75 consecutive type II diabetic patients with or without hypertension were recruited into the study. There were 18 (24.0%) hypertensive-diabetic and 12 (16.0%) normotensive-diabetic males and Thirty-four (45.3%) hypertensive-diabetic and 11 (14.0%) normotensive-diabetic were females. Hypertensive-diabetic males had significantly higher left ventricular mass compared to normotensive-diabetic counterpart 207.05 +/- 41.5g and 156.00 +/- 27.1g P = 0.001. Similarly, left ventricular mass index was found to be higher in hypertensive-diabetic males than their normotensive-diabetic counterpart 114.50 +/- 29.2g/m2 and 92.28 +/- 20.5g/m2 P = 0.014. Hypertensive-diabetic female significantly had higher LVM compared to the normotensive-diabetics 196.06 +/- 41.5g and 161.54 +/- 31.6g P = 0.016. Left ventricular mass index was also found to be higher in hypertensive-diabetic female than their normotensive counterpart 118.52 +/- 27.8g/m2 and 95.75 +/- 23.0g/m2 P = 0.019. Hypertensive-diabetics had predominantly concentric left ventricular hypertrophy compared to the normotensive-diabetics 36 (69.2. %) and 5 (21.7%) P = 0.001. CONCLUSION: The study reported that hypertensive-diabetics have predominantly concentric left ventricular hypertrophy, higher left ventricular mass and left ventricular mass index compared to normotensive-diabetic. Female hypertensive-diabetic had predominantly concentric left ventricular hypertrophy, while male hypertensive-diabetic and normotensive-diabetic had predominantly concentric left ventricular remodelling.

Detergent-salt resistance of LAP2alpha in interphase nuclei and phosphorylation-dependent association with chromosomes early in nuclear assembly implies functions in nuclear structure dynamics.

Lamina-associated polypeptide (LAP) 2 of the inner nuclear membrane (now LAP2beta) and LAP2alpha are related proteins produced by alternative splicing, and contain a common 187 amino acid N-terminal domain. We show here that, unlike LAP2beta, LAP2alpha behaved like a nuclear non-membrane protein in subcellular fractionation studies and was localized throughout the nuclear interior in interphase cells. It co-fractionated with LAP2beta in nuclear lamina/matrix-enriched fractions upon extraction of nuclei with detergent, salt and nucleases. During metaphase LAP2alpha dissociated from chromosomes and became concentrated around the spindle poles. Furthermore, LAP2alpha was mitotically phosphorylated, and phosphorylation correlated with increased LAP2alpha solubility upon extraction of cells in physiological buffers. LAP2alpha relocated to distinct sites around chromosomes at early stages of nuclear reassembly and intermediarily co-localized with peripheral lamin B and intranuclear lamin A structures at telophase. During in vitro nuclear assembly LAP2alpha was dephosphorylated and assembled into insoluble chromatin-associated structures, and recombinant LAP2alpha was found to interact with chromosomes in vitro. Some LAP2alpha may also associate with membranes prior to chromatin attachment. Altogether the data suggest a role of LAP2alpha in post-mitotic nuclear assembly and in the dynamic structural organization of the nucleus.

Whole blood culture for measuring mitogen induced T cell proliferation provides superior correlations with disease state and T cell phenotype in asymptomatic HIV-infected subjects.

Proliferative responses to a panel of mitogens were compared in parallel for two sources of cells, whole blood (WB) and conventionally prepared peripheral blood mononuclear cells (PBMC), obtained from asymptomatic HIV seropositive and control subjects. Weak but statistically significant correlations of the proliferative responses were observed. Use of either lymphocyte source produced significant differences in the proliferative responses between the HIV seropositive and control subjects, but the use of WB was more powerful, with a smaller sample size being required to discriminate between the proliferative responses of the two study groups. Furthermore, proliferative responses using WB gave strong and highly significant correlations with a number of important changes in the surface marker phenotype of the lymphocyte populations in the HIV seropositive subjects including CD4, CD8, CD4:CD8 ratio and certain CD8 subsets, whereas strong correlations were not observed with the PBMC. The response of WB lymphocytes to staphylococcal enterotoxin B (SEB) was highly reproducible and provided the best discrimination between HIV-infected and control subjects. We conclude that the use of WB for measuring lymphoproliferation is easy, rapid, accurate, and discriminative for assessing and following the changes in immune function which occur in HIV seropositive subjects, applicable in the clinical as well as in the research setting.

Immunosuppression by glucocorticoids: inhibition of production of multiple lymphokines by in vivo administration of dexamethasone.

Glucocorticoids are extremely potent immunosuppressive agents, capable of directly affecting the function of lymphocytes. We studied the effect of in vivo dexamethasone (DEX) administration on anti-CD3-induced lymphocyte proliferation and lymphokine production in mice. To characterize the kinetics and dose responsiveness of lymphocytes to DEX, splenocytes from BALB/c mice that had received a single dose of DEX in vivo were cultured in vitro with suboptimal and optimal concentrations of anti-CD3 monoclonal antibody. Cell proliferation in response to suboptimal concentrations of anti-CD3 was decreased by DEX doses of > or = 30 mg/kg; much higher doses (> or = 200 mg/kg) were required to inhibit cell proliferation in response to optimal anti-CD3 stimulation. Inhibition of suboptimal anti-CD3-stimulated proliferation was evident within 4 hr after DEX administration, was maintained for at least 24 hr, and was no longer evident at 7 and 14 days. Lymphokine secretion induced by optimal doses of anti-CD3 in vitro was differentially affected by in vivo DEX treatment. IL-1 alpha, IL-4, IL-6, IL-10, and IFN-gamma levels were decreased by treatment with low doses of DEX (30 mg/kg), whereas higher doses were required to inhibit production of IL-2, IL-3, and TNF. GM-CSF (granulocyte-macrophage-colony stimulating factor) was least susceptible to DEX inhibition. Low-dose (30 mg/kg) DEX treatment significantly reduced anti-CD3-stimulated production of most lymphokines tested at 4 and 12 hr; by 24 hr the levels of most lymphokines had begun to return to control values. Hence, our data indicate that administration of a single dose of DEX (30 mg/kg for 4 hr) results in significant suppression of lymphokine production and cell proliferation that precedes any significant cell loss and can be used as a reversible model of immunosuppression.

Identification of anti-CD3 antibodies that do not modulate antigen but induce mitogenesis and block the mixed lymphocyte reaction.

Using a panel of anti-CD3-TCR monoclonal antibodies (OKT3 A-E), it appears possible to separate the ability to cause surface antigen modulation from inhibition of MLR or induction of mitosis. OKT3D, an antibody that recognizes the CD3 antigen at a site that can be differentiated from the epitopes recognized by other members of this panel by competition binding, does not cause antigen modulation when incubated with human T cells for up to 3 days. Despite this, OKT3D is mitogenic and is capable of blocking MLR. Two different isotypes were produced from the OKT3D clone, IgG1 and IgG2b. The IgG2b isotype of OKT3D blocked MLR even in individuals unable to respond mitogenically to this antibody. Use of members of this panel may now permit dissection of the types of signals delivered by the CD3-TCR complex inducing mitosis, receptor modulation, and other T-cell responses.

Use of monoclonal antibodies to identify thymopoietin in cultured human thymic epithelial cells.

Murine monoclonal antibodies (mAbs) were developed to discriminate thymopoietin, a human thymic hormone, and thysplenin, a closely related molecule found in spleen. Three of these recognized both native and synthetic thymopoietin as well as thysplenin. Together they define two non-overlapping epitopes which withstand sodium dodecyl sulfate denaturation and can be detected by western blotting. We used these three mAbs to demonstrate the production of thymopoietin by cultured thymic epithelial cells for up to several weeks. Three additional mAbs were selective for thysplenin. Highly specific mAbs will be useful for characterizing further these physiologically distinct polypeptides.

OKT3E, an anti-CD3 antibody that does not elicit side effects or antiidiotype responses in chimpanzees.

Chimpanzees were injected with OKT3 and two other anti-CD3 antibodies, OKT3D and OKT3E. Both of the new antibodies were of the mouse IgG2b isotype. Administration of the antibodies was identical to the clinical regimen used for OKT3 in humans: 5 mg i.v., daily for 10 consecutive days. All animals were monitored for fever during administration of the antibodies, and blood samples were taken throughout the treatment period for monitoring the effects of the antibodies on peripheral lymphocyte subsets and the appearance of circulating cytokines. OKT3 produced similar clinical effects to those observed in humans; fever (2/3), as well as elevations in cytokines were observed. As in humans, peripheral T cells were cleared with the first dose and remained absent or modulated of their T cell receptor molecules throughout treatment. OKT3D, IgG2b also produced fevers (2/3) and elevations of cytokines. Although it also cleared circulating T cells with the first dose and T cell counts remained low throughout treatment, remaining circulating T cells were coated with administered antibody and were able to reexpress the CD3 antigen. OKT3E, IgG2b produced no temperature elevations and no elevations in cytokines. Although it cleared the circulation of T cells with the first does, cells reappeared during treatment, modulated of their CD3 antigens or coated with the administered antibody. All three antibodies raised antimouse antibodies, and OKT3 and OKT3D also produced blocking antiidiotype antibodies. OKT3E treatment did not result in anti-OKT3E blocking antibodies.

Flow cytometric resonance energy transfer measurements support the association of a 95-kDa peptide termed T27 with the 55-kDa Tac peptide.

Two monoclonal antibodies (OKT27 and OKT27b) have been produced that react with distinct epitopes of a 95-kDa peptide. The T27 antigen is widely distributed, being expressed on B lymphocytes, monocytes, and adult T-leukemic cells but not on polymorphonuclear leukocytes or platelets. There was a low level of T27 expression on resting T cells that increased on T-cell activation. In preliminary studies, the OKT27b antibody coprecipitated a 55-kDa peptide, as well as the 95-kDa peptide, from the radiolabeled cells of the HuT 102B2 cell line. Preclearance with anti-Tac, a monoclonal antibody to the 55-kDa peptide of the multichain interleukin 2 receptor, removed the 55-kDa but not the 95-kDa peptide from subsequent OKT27b immunoprecipitates of HuT 102B2 extracts, suggesting the possibility that the T27 peptide was associated with the Tac peptide. However, the precipitation of the p55 Tac peptide by OKT27b was quite inconsistent. Thus, additional information was sought using a flow cytometric energy transfer technique to provide a physical estimation of the proximity between the Tac and the T27 peptides. The flow cytometric version of the fluorescence resonance energy transfer technique permits the determination of inter- and intramolecular distances at 2- to 10-nm levels on a cell-by-cell basis. Using this approach, there was a mean energy transfer of 7.3% with HuT 102B2 cells when fluorescein isothiocyanate anti-Tac served as the donor and tetramethylrhodamine isothiocyanate OKT27 served as the acceptor. In contrast, there was no energy transfer in comparable studies observed when fluorescein anti-Tac and rhodamine anti-transferrin receptor antibodies were used. These observations support the conclusion that there is a close nonrandom proximity in HuT 102B2 cells between the 95-kDa peptide identified by the OKT27 monoclonal antibody and the p55 Tac peptide of the multichain interleukin 2 receptor.

Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen.

Mature T cells segregate phenotypically into one of two classes: those that express the surface glycoprotein CD4, and those that express the glycoprotein CD8. The CD4 molecule is expressed primarily on helper T cells whereas CD8 is found on cytotoxic and suppressor cells. A more stringent association exists, however, between these T-cell subsets and the major histocompatibility complex (MHC) gene products recognized by their T-cell receptors (TCRs). CD8+ lymphocytes interact with targets expressing class I MHC gene products, whereas CD4+ cells interact with class II MHC-bearing targets. To explain this association, it has been proposed that these 'accessory' molecules bind to monomorphic regions of the MHC proteins on the target cell, CD4 to class II and CD8 to class I products. This binding could hold the T cell and its target together, thus improving the probability of the formation of the trimolecular antigen: MHC: TCR complex. Because the TCR on CD4+ cells binds antigen in association with class II MHC, it has been difficult to design experiments to detect the association of CD4 with a class II molecule. To address this issue, we devised a xenogeneic system in which human CD4 complementary DNA was transfected into the murine CD4-, CD8- T-cell hybridoma 3DT-52.5.8, the TCR of which recognizes the murine class I molecule H-2Dd. The murine H-2Dd-bearing target cell line, P815, was cotransfected with human class II HLA-DR alpha, beta and invariant chain cDNAs. Co-culture of the parental T-cell and P815 lines, or of one parental and one transfected line resulted in a low baseline response. In contrast, a substantial increase in response was observed when CD4+ 3DT-52.5.8 cells were co-cultured with HLA-DR+ P815 cells. This result strongly indicates that CD4:HLA-DR binding occurs in this system and that this interaction augments T-cell activation.

Null cell identification and characterization with OKT16: an anti-p40 monoclonal antibody.

A murine monoclonal antibody, OKT16, specific for human lymphocytes of T lineage, was isolated by standard immunization and hybridization techniques. The distribution of the antigen defined by OKT16 was similar to the antigen reactive with monoclonal antibodies 3A1 and WT1. This identity of antigen targets was confirmed in an enzyme-linked immunosorbent assay system and by sequential immunoprecipitation. Under reducing conditions, OKT16 reacted with an antigen of 40K daltons; however, under nonreducing conditions this antigen appeared as an 84K-dalton molecule, which suggests that the p40 antigen exists as a disulfide-linked dimer. By indirect immunofluorescence, OKT16 reacted with a greater fraction of nonrosetting, non-B (null) lymphocytes than with antibodies to other T cell-specific proteins. Two-color immunofluorescence demonstrated the coexpression of the T16 antigen and the C3bi receptor on most null cells. The T10 antigen (found on cortical thymocytes and activated peripheral T cells) was restricted to most T16-bearing null cells and expression of the Fc receptor for aggregated IgG (defined by monoclonal antibody 73.1) was restricted to a major subset of T16-bearing null cells. The T cell-specific markers defined by OKT8, OKT11, and OKT17, as well as the monocyte marker defined by OKM5, were expressed by smaller subsets of OKT16-reactive null cells. These studies support by phenotypic analysis the functional heterogeneity ascribed to null cells. The 40K-dalton T16 antigen has the most extensive null cell representation of all the T lineage markers described to date.

Thymopoietin radioreceptor assay utilizing lectin-purified glycoprotein from a biologically responsive T cell line.

Radiolabeled thymopoietin that was biologically active and of high specific activity was prepared by a novel technique involving protection of free amino groups, selective excision of the protected N-terminal prolyl group with post-proline cleaving enzyme, reaction of the newly exposed alpha-amino group with a highly radioiodinated compound, and deprotection and purification of the polypeptide. Binding of this radiolabeled thymopoietin was not demonstrable by conventional techniques with cells, cell membranes, or solubilized cell membranes, apparently due to the presence of active proteases in these preparations. A glycoprotein with thymopoietin binding properties was prepared by lectin purification from the detergent-solubilized membranes of CEM cells, a human T cell line that responds to thymopoietin in vitro with increases in intracellular cyclic GMP. Presumably this procedure separated the thymopoietin binding protein from membrane proteases, thus permitting the development of a radioreceptor assay. Evidence is presented that the thymopoietin binding protein represents a thymopoietin receptor that is probably related to the mediation of immunoregulatory actions of thymopoietin on a subset of peripheral T cells.