Partial hypoxanthine-guanine phosphoribosyltransferase deficiency presenting as acute renal failure

Hyperuricemia and secondary urate nephropathy are uncommon in the paediatric setting outside of tumour lysis syndrome. We describe the case of a 12-year-old boy who presented at 3 years of age with acute renal failure. The cause of this remained unknown until the development of uric acid renal calculi 9 years later. This, and the availability of the previously unknown family history, provided the subsequent diagnosis of partial hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. Detailed family history is important for early detection of this heterogeneous group of disorders. Early treatment may minimise long-term renal morbidity and mortality from renal insufficiency.     

Role of O6-alkylguanine-DNA alkyltransferase in protecting against 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-induced long-term toxicities

O6-alkylguanine-DNA alkyltransferase (AGT) protects from the mutagenic and toxic lesions induced by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), and in many tumors, AGT overexpression provides a means of resistance. To circumvent this, O6-benzylguanine, an inactivator of AGT, has been developed and is currently in clinical development with BCNU; however, the potential long-term toxicities associated with this treatment are unknown. With the inactivation of AGT by O6-benzylguanine, a higher number of toxic and mutagenic O6-alkylguanine lesions introduced by methylating or chloroethylating agents would be expected. In this study, cohorts of mice were treated with vehicle, O6-benzylguanine (30 mg/kg), BCNU alone (low dose of 15 mg/kg or high dose of 50 mg/kg), or O6-benzylguanine (30 mg/kg) plus BCNU (15 mg/kg) and followed for 12 months post-treatment. Mice treated with O6-benzylguanine plus BCNU or high-dose BCNU died significantly earlier (p < 0.0001) than mice in the other three cohorts with a median survival of 8.3 (O6-benzylguanine plus BCNU) and 7.9 months (high-dose BCNU). Histopathologic sections of tissues revealed that the most common morphological diagnosis in animals treated with O6-benzylguanine plus BCNU (15 mg/kg) or BCNU (50 mg/kg) was cytomegaly in the lung with greater severity observed in mice receiving the combination O6-benzylguanine plus BCNU. Four of five mice analyzed in this cohort had alveolar histiocytosis, with one also having alveolar edema. In contrast, liver and kidney toxicity was only observed in mice treated with BCNU (50 mg/kg). These results suggest that O6-benzylguanine enhances long-term pulmonary toxicity associated with BCNU in mice.     

Cardiovascular response in Anemia

Objective: To study the functional consequences of nutritional anemia by evaluating the exercise performance in these children.Methods: The study was conducted on 30 each of anemic and normal children of both sexes aged between 7 and 14 years. Relevant history was taken, and detailed examination was done. These children were classified according to severity of anemia based on hemoglobin estimation as mild (10–11.9 g/dl), moderate (7–9.9 g/dl) and normal (>12g/dl). Children with severe anemia (Hb <7g/dl), heart disease, non-nutritional anemia, acute febrile or respiratory illness were excluded. The subjects were tested on Mortara X Scribe colour stress treadmill using the modified Bruce protocol. Continuous computerised electrocardiographic analysis was done. The parameters studied included heart rate, systolic blood pressure, double product (DP = HRxSBP), ECG changes, metabolic equivalents (METS) and exercise duration. The end point of the test was a HR of 170/min (non-fatigue group) or inability to perform further (fatigue group). Statistical analysis was done by appropriate tests.Results: Fifteen children each with mild and moderate anemia and 30 age-matched controls were enrolled in the study. There was no significant difference in the resting HR, exercise duration or DP between the cases and controls. Thirty-one children reached the target HR (non-fatigue group). The end-point HR was significantly lesser among the anemic children in the fatigue group (P 0.04). The percent gain of SBP, at peak exercise (P 0.0007) and recovery SBP as percent of resting SBP (p 0.006) were significantly more in the anemic children, more so in the mildly anemic ones. Lesser METS was achieved by anemics as compared to controls (P 0.04). ECG changes occurred significantly more often in anemic children, 53.8% of those with changes being moderately anemic, the main abnormality being ST depression. None developed arrhythmia during exercise testing.Conclusion: The cardiovascular response to physical exercise is compromised in children with nutritional anemia and hence these children may never attain their full potential in various school activities. Prevention of anemia should be a priority in school going children     

Responding to the threat of chronic diseases in India

At the present stage of India's health transition, chronic diseases contribute to an estimated 53% of deaths and 44% of disability-adjusted life-years lost. Cardiovascular diseases and diabetes are highly prevalent in urban areas. Tobacco-related cancers account for a large proportion of all cancers. Tobacco consumption, in diverse smoked and smokeless forms, is common, especially among the poor and rural population segments. Hypertension and dyslipidaemia, although common, are inadequately detected and treated. Demographic and socioeconomic factors are hastening the health transition, with sharp escalation of chronic disease burdens expected over the next 20 years. A national cancer control programme, initiated in 1975, has established 13 registries and increased the capacity for treatment. A comprehensive law for tobacco control was enacted in 2003. An integrated national programme for the prevention and control of cardiovascular diseases and diabetes is under development. There is a need to increase resource allocation, coordinate multisectoral policy interventions, and enhance the engagement of the health system in activities related to chronic disease prevention and control.     

Pseudoaneurysm of homograft placed in right ventricular outflow tract

Pseudoaneurysm of the right ventricular outflow tract after homograft placement is an infrequent complication after intracardiac repair for tetralogy of Fallot. We report two cases of pseudoaneurysm of right ventricular outflow tract after homograft placement for surgical repair of tetralogy of Fallot with pulmonary atresia.     

PneumoADIP: an example of translational research to accelerate pneumococcal vaccination in developing countries

Historically, the introduction of new vaccines in developing countries has been delayed due to lack of a coordinated effort to address both demand and supply issues. The introduction of vaccines in developing countries has been plagued by a vicious cycle of uncertain demand leading to limited supply, which keeps prices relatively high and, in turn, further increases the uncertainty of demand. The Pneumococcal Vaccines Accelerated Development and Introduction Plan (PneumoADIP) is an innovative approach designed to overcome this vicious cycle and to help assure an affordable, sustainable supply of new pneumococcal vaccines for developing countries. Translational research will play an important role in achieving the goals of PneumoADIP by establishing the burden of pneumococcal disease and the value of pneumococcal vaccines at global and country levels. If successful, PneumoADIP will reduce the uncertainty of demand, allow appropriate planning of supply, and achieve adequate and affordable availability of product for the introduction of pneumococcal vaccines. This model may provide a useful example and valuable lessons for how a successful public-private partnership can improve global health.