Comparative Study of the Antibacterial Activity of N, N-Diethylamido Substituted p-Toluenesulfonamides to their α-Toluenesulfonamide Counterparts.

Reaction of p-toluenesulfonyl chloride with amino acids gave sulfonamides p-T1a-k which upon amidation afforded p-T2a-k. Similarly, treatment involving α-toluenesulfonyl chloride and amino acids afforded the sulfonamides α-T1a-k. These two classes of sulfonamides were synthetically modified at their COOH end position to achieve N,N-diethylamido substituted p-toluenesulfonamides p-T2a-k and α-toluenesulfonamides α-T2a-k, respectively. The chemical structures of the compounds were validated with IR, Mass spectra, NMR as well as elemental analytical data. Both classes of compounds were screened against Escherichia coli and Staphylococcus aureus and their activity werecompared. It was remarkable to note that the α-toluene sulfonamides α-T2a-k were more active than their p-toluenesulfonamide counterparts p-T2a-k. Compound 1-(benzylsulfonyl)-N,N-diethylpyrrolidine-2-carboxamide α-T2a was the most potent antibacterial compound on S. aureus with MIC value of 3.12 µg mL(-1) while N,N-Diethyl-3-phenyl-2-(phenylmethylsulfonamide) propanamide α-T2j emerged as the best antibacterial motif against E. coli with MIC value of 12.5 µg mL(-1). Hence, these compounds especially the α-toluenesulfonamide core structural templates are good candidates for further study for future drug discovery.

Determinants and perception of cardiovascular risk factors among secondary school teachers in Oyo state Nigeria.

BACKGROUND: Cardiovascular diseases (CVD) are common. They constitute an increasing cause of morbidity and mortality. Knowledge of the risk factors may lead to attitudinal change with consequent reduction in prevalence. Secondary school teachers constitute a large literate workforce that has direct influence on students and indirectly on their parents and guardians. OBJECTIVE: The aim of this study is to investigate the knowledge of cardiovascular risk factors among secondary school teachers in Oyo State, Nigeria and also the determinants of such knowledge. METHODS: Three hundred and fifty eight secondary school teachers from the Akinyele local government of Oyo State Nigeria completed a questionnaire seeking such information as which diseases constitute CVD and also identify risk factors for CVD. The determinants of such knowledge were investigated by the log likehood ratio using logistic regression. Two hundred and fifteen civil servants matched for age, sex and qualifications were enrolled as controls. RESULTS: Of the 358 teachers, 12.3% were current smokers, 32.1% drank alcohol. More of the civil servant controls patronized fast food joints. Over 80% of the teachers performed exercise regularly, majority being 'walking' (66.2%). Hypertension (84.5%) and heart attack (87.6%) were the most correctly identified CVD. The least correctly identified was peripheral vascular disease (18.6%). The longer the years of teaching, specialization in pure science and being male the more likely the knowledge of sedentary living as a risk factor. Other variables that reached statistical significance include knowledge of stress, smoking and advanced age. CONCLUSION: Generally the knowledge of the teachers is inadequate about CVD and the risk factors. Qualification in pure science and years of teaching did not radically affect this knowledge. The knowledge base of the teachers needs to be improved.

Effect of systemic hypertension on right ventricular morphology and function: an echocardiographic study.

BACKGROUND: Hypertension is an important cardiovascular risk factor worldwide. It is associated with left ventricular hypertrophy (LVH). Both diastolic and systolic dysfunction may occur in hypertensive heart disease. The ventricles are structurally and functionally interdependent on each other. This was an echocardiographic study intended to describe the impact of left ventricular pressure overload and hypertrophy due to hypertension on right ventricular morphology and function. METHODS: One hundred subjects with systemic hypertension and 50 age- and gender-matched normotensive control subjects were used for this study. Two-dimensional (2-D), M-mode and Doppler echocardiographic studies were done to evaluate the structure and function of both ventricles. Data analysis was done using the SPSS 16.0 (Chicago, Ill). Statistical significance was taken as p < 0.05. RESULTS: Age and gender were comparable between the two groups. Hypertensive subjects had significantly increased left ventricular end-diastolic dimensions, posterior wall thickness, interventricular septal thickness, left atrial dimensions and left ventricular mass and index. The mitral valve E/A ratio was reduced among hypertensive subjects when compared to normal controls (1.15 ± 0.75 vs 1.44 ± 0.31, respectively; p < 0.05). A similar pattern was found in the tricuspid E/A ratio (1.14 ± 0.36 vs 1.29 ± 0.30, respectively; p < 0.05). Hypertensive subjects also had reduced right ventricular internal dimensions (20.7 ± 8.0 vs 23.1 ± 3.1 mm, respectively; p < 0.001) but similar peak pulmonary systolic velocity. The mitral e/a ratio correlated well with the tricuspid e/a ratio. CONCLUSION: Systemic hypertension is associated with right ventricular morphological and functional abnormalities. Right ventricular diastolic dysfunction may be an early clue to hypertensive heart disease.

Correlates of cardiac autonomic neuropathy in Nigerian patients with type 2 diabetes mellitus.

Cardiac Autonomic Neuropathy (CAN) contributes significantly to increased cardiovascular morbidity and mortality in type2 diabetic patients. This manuscript aims to study the prevalence of CAN in T2DM patients in our environment and identify factors that correlate with and predict development of CAN. This is with the intention to prevent and intervene in these factors. One hundred and eight (108) T2DM patients were screened and investigated by the standard six non-invasive tests including heart rate variability, QTc and Valsalva manouvre. Patients who had abnormality in more than 2 of the tests were adjudged to have CAN. They were statistically compared with those without CAN. Thirty- seven (34.2%) patients had CAN. The commonest abnormality was in heart rate response to standing (76.9%) There was no significant difference in the mean age and sex of those with CAN and those without. Though significantly more males had CAN, when sex was entered into the logistic regression it did not correlate with CAN. Poor short-term glycaemic control as demonstrated by fasting blood glucose (130.87 + 56.1 vs 94.24 + 48.9 mg%, p < 0.05); serum creatinine (1.23 + 0.52 vs 0.86 + 0.39 mg%, p<0.05), presence of hypertension and first degree family history were significantly more in patients with CAN. There was more than 2-fold increased risk of developing CAN when serum creatinine was greater than 1.5 mg% (OR 2.013, 95% CI 0.543-2.657) and when FBG was more than 120 mg% (OR 2.106, 95% CI 0.834-2.897). CAN is common in our patients with T2DM. It is more prevalent in those with hypertension, first degree family history and renal damage. Poor short-time glycaemic control was also a contributory factor.

A clinical study of pattern and factors affecting outcome in Nigerian patients with advanced heart failure.

BACKGROUND: Advanced heart failure (AHF) accounts for about 25% of all cases of heart failure in Nigeria and is associated with a high mortality rate. OBJECTIVE: To undertake a clinical study of the pattern and outcome of AHF in our hospitalised patients and to determine the parameters associated with mortality and survival in these patients. METHOD: Eighty-two patients with AHF were studied between January 2003 and December 2005. Baseline blood chemistry and haemodynamics were determined. A congestion score, including orthopnoea, elevated jugular venous pressure, oedema, ascites and loud P2, was derived as well as a low perfusion score. Mortality was computed and risk estimated using the Pearson coefficient and log-ranking test. Cox regression analysis was used to identify the predictors of survival. RESULTS: AHF accounted for 43.6% of all hospitalised heart failure patients, with a total mortality of 67.1%. Hypertension was the commonest cause of AHF. The parameters associated with increased mortality rates included age (r = 0.671; p = 0.02), presence of atrial fibrillation (r = 0.532; p = 0.045) and estimated glomerular filtration rate (r = -0.486, p = 0.04). The majority of patients (54.8%) were in the 'wet and cold' congestion category. The congestion score correlated with mortality. The indices of survival included lower age, lower systolic blood pressure, being literate and lower congestion score. CONCLUSION: AHF was common in our cohorts of hospitalised heart failure patients and it was associated with a high mortality rate.

Effects and outcome of haemodialysis on QT intervals and QT dispersion in patients with chronic kidney disease.

Cardiovascular complications and sudden cardiac death are common in patients with chronic kidney disease and those on haemodialysis. This is often associated with prolonged QT(c) and QT(c) dispersion intervals. Forty-two patients on haemodialysis were compared with 45 control subjects to study the effect of haemodialysis on these ECG parameters and to compare mortality rates of those with excessively prolonged QT(c) and QT(c) dispersion. Maximum QT(cd), QT(d) and QT(c) dispersion increased with dialysis although these did not reach statistical significance. The maximum QT(c) was longer than 440 ms in 71.4% of patients post-dialysis, with a mortality rate of 73.3%. This was not statistically different from a mortality of 66.7% for those patients with maximum QT(c) less than 440 ms. Some (40.4%) of the patients had a QT(c) dispersion longer than 80 ms; the mortality rate of these (70.5%) was not statistically different from 68.0% for those with shorter QT(c) dispersion. Arrhythmia was rare in all cases. Patients with left ventricular hypertrophy (LVH) had the longest QT(c) dispersion and a statistically higher mortality rate. The in-hospital mortality in our patients was high (69.0%) but this might have been related to late presentation and limited facilities and not necessarily to acute cardiovascular complications of prolonged QT(c) dispersion.

Comparison of the effects of arm position and support on blood pressure in hypertensive and normotensive subjects.

One hundred and twenty-three hypertensive patients were compared with 120 normotensive subjects, to study the effect of arm position and arm support on blood pressure (BP). The BP tended to increase from the sitting to the standing position in both groups, except when subjects were standing with the arm held out perpendicular to the body, in which case the BP decreased. The lowest standing recordings were observed when the elbow was slightly flexed and supported at this position. The highest BP was observed in the standing position with the arm hanging at the side. Differences in the systolic BP between those with the arm hanging and when it was perpendicular to the torso, or flexed and supported at the elbow were 7.45 mmHg in hypertensives (p = 0.002) and 16.35 mmHg in normotensives (p < 0.0001). Similar figures for diastolic BP were 7.84 mmHg for hypertensives (p < 0.0001) and 9.81 mmHg for normotensives (p < 0.0001). Failure to support the arm at the elbow, even when it was positioned perpendicularly to the torso, led to an increase of 4.87/4.81 mmHg in hypertensives and 7.61/2.83 mmHg in normotensives. Arm position and arm support affect the accuracy of BP measurements. The effect of arm position is more than that of arm support, although they are additive, and more in normotensives. Healthcare providers should adhere to recommended guidelines for BP measurement.

Cardiovascular risk factors in type 2 diabetic Nigerians with clinical diabetic nephropathy.

This study aimed to assess the distribution of cardiovascular risk factors among subjects with type 2 clinical diabetic nephropathy, since in diabetic subjects, the excess mortality in cardiovascular events is primarily related to nephropathy. The study group consisted of 162 subjects with type 2 diabetes mellitus and persistent proteinuria, and the control group was 80 type 2 diabetic subjects without nephropathy. In the study group there were 81 male and 81 female subjects whose mean age was 53.4 +/- 6.3 years. There was no significant consumption of alcohol and cigarette use in the population. The mean waist-hip ratio (WHR) was 0.97 and 0.96 in male and female subjects, respectively. The mean body mass index (BMI) of the subjects was 25.5 +/- 5.2 (males: 24.4 +/- 4.3, females: 27.2 +/- 5.5). A total of 106 subjects, made up of 45 male (27.8%) and 61 female (37.7%) subjects, were hypertensive as compared with 16 controls (20%). There was a significant difference in systolic blood pressure (p < 0.05) between the obese and non-obese subjects. One hundred and thirty three subjects (82.1%) had serum total cholesterol below 200 mg% as compared with 74 (92.5% ) in the control. Seventy-eight subjects (48.1%) had left ventricular hypertrophy. Males had a higher tendency of developing left ventricular hypertrophy (p = 0.04). Stroke and peripheral vascular disease respectively occurred more commonly in type 2 diabetes mellitus subjects with nephropathy [7 (4%) and 44 (27.2%)] compared to type 2 diabetic subjects without nephropathy [0 (0% ) and 9 (11.3% )] (p < 0.05). We found that there is a high prevalence of cardiovascular risk factors among Nigerian subjects with clinical diabetic nephropathy.

Pattern of occurrence of microalbuminuria among dippers and non-dippers (essential hypertensives) in a Nigerian university teaching hospital.

OBJECTIVES: Hypertensives who fail to manifest the normal circadian nocturnal fall in blood pressure have a higher incidence of cardiovascular complications, early glomerular injury and microalbuminuria. This study aims to quantify the proportion of dippers and non-dippers among the essential hypertensive population, and determine the frequency of occurrence of micro-albuminuria among them. MATERIALS AND METHODS: Early morning urine specimens were taken from 50 patients with essential hypertension and 20 healthy, normotensive subjects. Combined negative results from albustic strip testing and sulfosalicylic acid tests were taken as excluding microalbuminuria. While collecting urine for 24-hour urinary protein and creatinine clearance, hourly blood pressure readings were recorded. Readings obtained between 07:00 and 23:00 were taken as daytime blood pressure readings, whereas readings obtained between 23:00 and 07:00 were considered night-time blood pressure. Dippers were considered to be those patients in whom the difference between mean daytime systolic/diastolic blood pressure and mean night-time systolic/diastolic blood pressure was 10/5mm Hg or more. RESULTS: Thirty-six (72%) and 14 (28%) patients with essential hypertension fulfilled the criteria for dippers and non-dippers, respectively. The night-time systolic and diastolic blood pressures were significantly higher in non-dippers than in dippers (P < 0.05). The mean daytime systolic and diastolic blood pressures were not different between these two groups. Twenty-nine out of 36 (80.6%) urinary specimens from dippers were without microalbuminuria, against six out of 14 (42.9%) specimens from non-dippers, p < 0.05. Eighteen out of 20 controls (90%) were without microalbuminuria. CONCLUSION: This study demonstrated that about 28% of the local essential hypertensive population was non-dippers and 57.1% of these had microalbuminuria with the attendant cardiovascular and renal risks.

Ability of Nigerian hypertensive patients to perceive changes in their blood pressure.

The objective of this study was to examine the ability of hypertensive patients to predict correctly when their blood pressure (BP) was elevated, and the symptoms they felt when such changes occurred. We also sought to determine whether literacy levels or the number of years that a patient had been diagnosed as hypertensive had a correlation with whether a patient was a predictor and whether he was an accurate predictor. One hundred and seventy-seven patients were studies, of which 101 (57.1%) claimed they could tell when their BP was elevated. Only 45 (44.5%) of the predictors were right in their prediction. Although being literate and longer time of being hypertensive was found to be likely to make a patient a predictor, neither of these variables was likely to make a predictor accurate. Predictors were also likely to be younger than non-predictors. The symptoms the patients were likely to complain about as denoting a rise in BP included headache (20.4%), weakness/tiredness (20.4%) and palpitation (18.5%). The study has shown that the majority of predictors were not accurate and so hypertensive patients should be counseled not to depend on how they feel but to visit physicians regularly for BP checks.

Spectrum and outcome of clinical diseases in adults living with AIDS at the Ogun State University Teaching Hospital.

OBJECTIVES: To evaluate the changing frequency of HIV/AIDS amongst medical admissions as well as the spectrum and outcome of clinical diseases among these patients. DESIGN: Retrospective study. SETTING: Tertiary hospital in Nigeria. PARTICIPANTS: Two hundred and six People Living With AIDS (PLWA) admitted at the medical wards during the period 1992 to 2002. INTERVENTION: Treatment was symptomatic in all patients and where appropriate, specific treatment was administered for indicator diseases. Highly Active Anti-retroviral Therapy (HAART) was not used. MAIN OUTCOME MEASURES: Mortality within six months of diagnosis. RESULTS: PLWA constituted 4.2% of all medical admissions. The frequency increased from 0% in 1992 to 7.6% in 2001, and dropped to 5% by the year 2002. Seventy patients (34%) died within six months of diagnosis. RESULTS: This study has demonstrated an increasing frequency of HIV/AIDS amongst our medical in-patients from none in 1992 to 7.6% in 2001, and thereafter, a decline in 2002. We suspect that this decline could be a reflection of the health education on HIV, its increasing awareness and the widespread utilisation of effective control measures. Furthermore, the administration of highly active anti retroviral therapy (HAART) to a segment of PLWA in Sagamu by the community medicine department could be contributory. CONCLUSION: A community based study would be needed to assess the efficacy or otherwise of these current control measures. The advent of saliva and urine tests for HIV detection would ease specimen collection and increase compliance and participation at the community level.

Selective ortho and benzylic functionalization of secondary and tertiary p-tolylsulfonamides. Ipso-bromo desilylation and Suzuki cross-coupling reactions.

Kinetic vs thermodynamic deprotonation studies on secondary and tertiary sulfonamides 1 and 2 using n-BuLi have been carried out. While both 1 and 2 show kinetic ortho-metalation, thermodynamic conditions lead to ortho and benzylic deprotonation, respectively (Figures 1 and 2). Metalation of 1 using the n-BuLi/KOtBu superbase led to regioselective benzylic metalation (Figure 4); LDA deprotonation was also briefly explored. Application of the developed conditions allows the synthesis of diverse sulfonamide products 5a-e, 6a-e, 7a,b, and 8a-e. Ipso-bromo desilylation reactions afford sulfonamides 9a,b while Suzuki cross-coupling reactions furnish biaryl sulfonamides 11a-c.

Pattern and outcome of medical admissions at the Ogun State University Teaching Hospital, Sagamu--a three year review.

This is a three-year retrospective study of the pattern and outcome of acute medical admissions at the Ogun State University Teaching Hospital, Sagamu. Our findings showed that there were 1,938 admissions over the study period of which 1,044 (54%) were females and 894 (46%) were males. The ages of the patients ranged between 12 to 86 years with a mean of 49 +/- 1.7 years. The age range was 14 to 80 years for males with a mean of 47 +/- 6.1 years and 12 to 86 years for females with a mean of 49 +/- 4.5 years. The length of stay was between 5 to 25 days with a mean of 15 +/- 0.5 days. There were 16 patients per bed per year with a turn around of 8 days and bed occupancy of 65% 194 (10%) patients discharged themselves against medical advice and there were 488 (25%) deaths. The interval between admission and death ranged between 4 to 7 days with a mean of 5.5 +/- 0.07 days. Indications for admissions were infectious diseases (38%), neurological disorders (19.6%) gastro-intestinal disorders (11%), genito-urinary tract disorders (10.2%) endocrine disorder (10%), cardiovascular disorders (9.9%), respiratory disorders (6.4%) and haematological disorders (4.9%). Tuberculosis accounted for 10% of total medical admissions and was the commonest disease entity responsible for medical admissions. Acquired immuno deficiency syndrome (AIDS) constituted 1.8% of medical admissions. Mortality was highest for infections accounting for 32% of deaths while malaria accounted for the lowest. The reasons for the relative frequency and mortality are adduced. The study recommends improvement of preventive strategies towards communicable diseases in the community and encourages better admission policy, provision of appropriate facilities and manpower to improve the hospital services.