Reducing the costs of surgical correction of congenitally malformed hearts in developing countries

A large number of patients in developing countries require surgical correction of congenitally malformed hearts. Unfortunately, only a limited number of centres offer these patients surgery at an affordable cost. In this review, we discuss the problems in managing these patients, with an emphasis on reduction of costs, so that the maximum number of patients can benefit. It is apparent that containing costs requires a multipronged approach, which begins with timely referral, and continues with early surgical correction and adequate postoperative care carried out in a scientific manner. Indigenization, innovation, training of manpower, and building a team, are essential to cut the costs, and to improve the quality of care.     

Multiple saccular aortic aneurysms following the arterial switch operation

We report a 3‐month‐old male presenting with multiple aortic aneurysms arising de novo 2 months following the arterial switch operation. Successful repair of the aneurysms was performed under total circulatory arrest and at seven years follow‐up, the patient has no recurrence.     

Prevalence of hypertension among Indian adults: Results from the great India blood pressure survey

ObjectiveHypertension is the most important risk factor for cardiovascular morbidity and mortality. There is limited data on hypertension prevalence in India. This study was conducted to estimate the prevalence of hypertension among Indian adults.MethodsA national level survey was conducted with fixed one-day blood pressure measurement camps across 24 states and union territories of India. Hypertension was defined as systolic blood pressure (BP) ≥140 mmHg or a diastolic BP ≥90 mmHg or on treatment for hypertension. The prevalence was age- and gender-standardized according to the 2011 census population of India.ResultsBlood pressure was recorded for 180,335 participants (33.2% women; mean age 40.6 ± 14.9 years). Among them, 8,898 (4.9%), 99,791 (55.3%), 35,694 (11.9%), 23,084 (12.8%), 9,989 (5.5%), and 2,878 (1.6%) participants were of the age group 18–19, 20–44, 45–54, 55–64, 65–74, and ≥ 75 years, respectively. Overall prevalence of hypertension was 30.7% (95% confidence interval [CI]: 30.5, 30.9) and the prevalence among women was 23.7% (95% CI: 23.3, 24). Prevalence adjusted for 2011 census population and the WHO reference population was 29.7% and 32.8%, respectively.ConclusionThere is a high prevalence of hypertension, with almost one in every three Indian adult affected.     

Impact of CYP2D6, CYP3A5, CYP2C9 and CYP2C19 polymorphisms on tamoxifen pharmacokinetics in Asian breast cancer patients

AIM

To investigate the impact of genetic polymorphisms in CYP2D6, CYP3A5, CYP2C9 and CYP2C19 on the pharmacokinetics of tamoxifen and its metabolites in Asian breast cancer patients.

METHODS

A total of 165 Asian breast cancer patients receiving 20 mg tamoxifen daily and 228 healthy Asian subjects (Chinese, Malay and Indian; n = 76 each) were recruited. The steady-state plasma concentrations of tamoxifen and its metabolites were quantified using high-performance liquid chromatography. The CYP2D6 polymorphisms were genotyped using the INFINITI™ CYP450 2D6I assay, while the polymorphisms in CYP3A5, CYP2C9 and CYP2C19 were determined via direct sequencing.

RESULTS

The polymorphisms, CYP2D6*5 and *10, were significantly associated with lower endoxifen and higher N-desmethyltamoxifen (NDM) concentrations. Patients who were *1/*1 carriers exhibited 2.4- to 2.6-fold higher endoxifen concentrations and 1.9- to 2.1-fold lower NDM concentrations than either *10/*10 or *5/*10 carriers (P < 0.001). Similarly, the endoxifen concentrations were found to be 1.8- to 2.6-times higher in *1/*5 or *1/*10 carriers compared with *10/*10 and *5/*10 carriers (P≤ 0.001). Similar relationships were observed between the CYP2D6 polymorphisms and metabolic ratios of tamoxifen and its metabolites. No significant associations were observed with regards to the polymorphisms in CYP3A5, CYP2C9 and CYP2C19.

CONCLUSIONS

The present study in Asian breast cancer patients showed that CYP2D6*5/*10 and *10/*10 genotypes are associated with significantly lower concentrations of the active metabolite of tamoxifen, endoxifen. Identifying such patients before the start of treatment may be useful in optimizing therapy with tamoxifen. The role of CYP3A5, CYP2C9 and CYP2C19 seem to be minor.     

Probing glucocorticoid-dependent osteogenesis in rat and chick cells in vitro by specific blockade of osteoblastic differentiation with progesterone and RU38486

Glucocorticoids and sex-steroids can modulate osteogenesis in vivo and in vitro. Although the effects of glucocorticoids on bone cells in vitro have been described in detail, the role of sex-steroids is not as well defined. We examined whether sex-steroids influence bone metabolism indirectly by regulating glucocorticoid effects on bone. Interactions of the sex-steroid progesterone or its analog RU38486 with the glucocorticoid dexamethasone (dex) were studied in functional assays of osteogenesis. Three osteoblastic models were evaluated:(1) the rat bone marrow stromal cell (RBMC) nodule system; (2) the chick periosteal osteogenesis (CPO) model; and (3) ROS 17/2.8 cells. RU38486, progesterone, and unlabelled dex competitively inhibited ³H-dex uptake by ROS 17/2.8 cells as well as its (³H-dex) binding to cytosol preps. Both RU38486 and progesterone inhibited dex-induced increases in alkaline phosphatase in CPO cultures, in RBMC cultures, and in ROS 17/2.8 cells. Dex-induced decreases in cell proliferation in ROS 17/2.8 cells were reversed by RU38486 but dex-induced increases in proliferation in the CPO model were not affected. In CPO cultures, dex-induced increases in collagen synthesis were inhibited completely by RU38486 and progesterone, Dex-dependent nodule formation in the RBMC was blocked by RU38486. Both RU38486 and dex mediated reduction of calcium uptake in the CPO model but did not affect mineralized tissue area. The data indicate that RU38486 and progesterone competitively inhibit dex-mediated stimulation of osteogenesis in vitro; this inhibition is exerted on early but not late stage differentiation events of osteoprogenitor cells. © 1995 Wiley-Liss, Inc.     

Use of extracorporeal membrane oxygenator support to salvage an infant with anomalous left coronary artery from pulmonary artery

Anomalous left coronary artery from pulmonary artery (ALCAPA) is a congenital acyanotic heart disease where the left coronary artery (LCA) arises from the pulmonary artery. This results in the LCA receiving blood supply from the low-pressure right ventricle having minimal extractable oxygen. The oxygen delivery to the left ventricle (LV) is severely hampered causing severe hypoxic LV dysfunction early in life. Early surgery prior to serious, irreversible LV dysfunction is the key to survival. Children with ALCAPA usually present in their first few weeks of life, with severe LV dysfunction. After surgical correction of the defect, the myocardium may not recover early from the presurgery myocardial dysfunction. We describe a case where extracorporeal membrane oxygenator was utilized as a means of ventricular support during this critical postoperative period resulting in a favorable outcome.     

Thyroid hormone supplementation following open-heart surgery in children

In patients undergoing open-heart surgery, abnormalities in thyroid hormone levels have been observed even in the absence of primary thyroid disease. These abnormal changes in thyroid hormone level and function have been found to be sufficient to affect myocardial performance and postoperative recovery. In the intensive care unit, postoperatively, it has been found that features such as low cardiac output, left ventricular dysfunction and prolonged ventilator support were associated with hypothyroidism. We reviewed the available literature on the effect of thyroid hormone supplementation in paediatric patients undergoing open-heart surgery under cardiopulmonary bypass and concluded that children after complex congenital cardiac surgery are at risk of developing a clinically significant hypothyroid state in the early postoperative period. In the literature where the effects of supplementation of thyroxine were studied, beneficial effects were observed in terms of reduced mechanical ventilation time, reduced inotropic support and intensive care unit stay, rapid achievement of negative fluid balance and early recovery. Supplementation with thyroid hormones enables a smoother postoperative recovery and is beneficial. The total duration of this therapy is, however, unclear.