Efficacy, Safety and Tolerability of Valsartan and Hydrochlorothiazide Compared to Valsartan and Amlodipine in Stage 2 Hypertension

Background: Hypertension is a growing medical and public health issue. The United States and European treatment guidelines have been issued to attain smooth control of hypertension in various categories of patients. It is a need of time to unveil safe combination therapies in various populations. Objectives: (i) To determine the efficacy of valsartan and hydrochlorothiazide versus valsartan and amlodipine (ii) To determine the safety and tolerability of both combinations. Materials & Methods: This experimental study was conducted at Shalamar Hospital Lahore. 126 patients with stage 2 hypertension were recruited from the medical outdoor of Shalamar Hospital Lahore after getting informed consent. In group A, 63 patients were given valsartan and hydrochlorothiazide. In group B, 63 patients were given valsartan and amlodipine. Blood pressure (BP) of both study groups was recorded on day zero, 2nd, 4th, and 8th weeks and the readings were entered on a Proforma. The efficacy of drug combinations was accessed in both groups by recording the change in mean systolic blood pressure (MSBP) and mean diastolic blood pressure (MDBP). The safety and tolerability of the drug combinations were assessed in terms of side effects and laboratory findings. Results: In group A, there was a 39±7mmzHg and 18±1mmHg decrease in MSBP and MDBP, respectively, from baseline BP. In group B, there was a 26.7±4mmHg and 14±2 mmHg decrease in MSBP and MDBP, respectively, from baseline BP. Both combinations were safe, and no significant difference in the efficacy of both combinations was observed after 8-week of treatment. Conclusion: Both combinations are effective for control of BP, but the valsartan and hydrochlorothiazide combination (group A) appears to have better tolerability and greater effect in decreasing BP as compared to the combination of valsartan and amlodipine (group B), although this difference is not statistically significant.  

Expression of Mismatch Repair Proteins in Colorectal Cancer at Aga Khan University Hospital, Nairobi

Introduction: Microsatellite instability is one of three molecular pathways described in the pathogenesis of colorectal carcinoma. The presence of microsatellite instability in patients with colorectal cancer has implications for prognosis and family counselling. Deficiency in mismatch repair genes leads to microsatellite instability and this can be reliably demonstrated in formalin fixed paraffin embedded tissue by methods, which include immunohistochemistry for the detection of mismatch repair proteins. Local data show a disproportionately large number of younger patients with colorectal cancer compared to that documented in Caucasians. Colorectal cancer in younger ages is often attributed to deficient mismatch repair. The objective of this study therefore, was to determine the proportion of colorectal cancers associated with the microsatellite instability pathway through detection of the mismatch repair proteins on immunohistochemistry. Materials and Methods: This was a retrospective study of 80 colorectal adenocarcinoma resection specimens received over a three-year period from January 2009 to January 2012. The mismatch repair gene mutation expression was analysed by immunohistochemical staining for products of mismatch repair genes. Associated clinical and pathologic characteristics were reviewed and documented. Results: The proportion of deficient mismatch colorectal cancer in the study was 19.4% [95% CI 11.7%-30.4%].There was a significant but weak association between mismatch repair gene protein expression and tumour grade, and tumour infiltrating lymphocytes (tumour grade Cramer’s V=0.263, p=0.031; tumour infiltrating lymphocytes Cramer’s V=0.246, p=0.044). Mismatch repair gene protein expression outcome showed significant but moderately strong association with the anatomic site of tumour, and tumour histological type (anatomic site Cramer’s V=0.469, p=0.001, tumour histological type Cramer’s V=0.469, p=0.001,). Conclusions: The study provides preliminary data of the contribution of the deficient mismatch repair molecular pathway of colorectal cancer in Kenya.