Hyperuricaemia does not impair cardiovascular function in healthy adults.

OBJECTIVE: To investigate the possibility that uric acid (UA) can impair endothelial function, an important surrogate for atherosclerosis. DESIGN: UA was administered locally or systemically to healthy adult men and women in a series of randomised placebo controlled studies. This temporarily raised serum UA concentrations, so that the potential effects of hyperuricaemia on mechanisms of cardiovascular disease could be studied. MAIN OUTCOME MEASURES: The effects of UA administration on basal blood flow and responses to locally administered acetylcholine, sodium nitroprusside, and L-N(G)-monomethylarginine were studied in the forearm vascular bed with venous occlusion plethysmography. The effects of hyperuricaemia on systemic vascular resistance, large artery compliance, and baroreflex sensitivity were examined by validated non-invasive techniques. RESULTS: UA administration caused a twofold increase in serum concentrations. However, there were no acute effects on haemodynamic variables, basal forearm blood flow, or nitric oxide dependent endothelial function. CONCLUSION: Unlike other risk factors associated with endothelial dysfunction, acute exposure to high concentrations of UA does not impair cardiovascular function in healthy men. These findings do not support a causal link between hyperuricaemia and atherosclerosis.

Ichthyosiform erythroderma and cardiomyopathy: report of two cases and review of the literature.

We report two children with ichthyosiform erythroderma who at the ages of 9 weeks and 8 years, respectively, developed dilated cardiomyopathy, which was fatal in one and required heart transplantation in the other. A link between these conditions is considered likely, either as a primary genetic syndrome or secondary to micronutrient deficiency and/or infection. Owing to its insidious onset, cardiomyopathy may be overlooked, or symptoms attributed to the other conditions such as severe infections and failure to thrive that are common in these patients. We therefore recommend that children with congenital erythroderma are monitored closely, clinically and with echocardiography, for cardiomyopathy.

Percutaneous transhepatic dual chamber pacing in children with Fontan circulation.

Permanent pacing is often required following the Fontan operation and is usually performed epicardially as there is no direct access to the ventricle from the systemic veins. Dual chamber endocardial pacing was achieved by the transhepatic approach in two children with Fontan circulation. The patients were a 7 year old boy with left atrial isomerism, single ventricle with pulmonary stenosis, interrupted inferior vena caval vein with azygous continuation, and direct drainage of the hepatic veins to the right sided atrium, and a 6 year old girl with tricuspid atresia. This approach to endocardial pacemaker implantation is potentially of considerable value in patients who do not have direct access to the ventricle from the systemic veins.

Heart transplantation for Barth syndrome.

Barth syndrome is an X-linked recessive disorder comprising dilated cardiomyopathy, muscular hypotonia, and cyclical neutropenia. Affected children usually die during infancy as a consequence of septicemia, cardiac failure, or both. We report a patient with Barth syndrome who underwent successful heart transplantation.

Percutaneous transluminal balloon angioplasty of abdominal aortic coarctation in an infant.

Abdominal aortic coarctation is rare in children. We report successful percutaneous transluminal balloon angioplasty of an abdominal aortic coarctation in an infant who presented with heart failure.

Heart transplantation for dilated cardiomyopathy.

Between 1988 and 1994, 23 patients underwent heart transplantation for dilated cardiomyopathy. The age of the 13 boys and 10 girls was from 8 months to 16 years (mean 7.1 years). Selection criteria included failure to thrive despite maximal antifailure treatment and/or intravenous inotrope dependence. The aetiology of cardiomyopathy was idiopathic (n = 13), congenital (n = 3), anthracycline induced (n = 4), Barth's syndrome (n = 1), and maternal systemic lupus erythematosus (n = 2). The waiting period of heart transplantation ranged from one day to 147 days (mean 22 days). Maintenance immunosuppression included cyclosporin, azathioprine, and prednisolone. Follow up after transplantation was from one month to 62 months (median 27 months) with a mean actuarial survival of 95% at one year and 87% at three years. Four patients developed coronary artery disease, one of whom died as a consequence 15 months after heart transplantation. Heart transplantation has emerged as an acceptable therapeutic option, at least in the short term, for patients with dilated cardiomyopathy.

In vitro enhancement of adriamycin cytotoxicity in human myeloid leukemia cells exposed to verapamil.

The natural resistance of human chronic myeloid leukemia cells to adriamycin (ADR) was overcome by using the cell membrane modulator verapamil (VRP). The studies were done in vitro. [3H] thymidine incorporation inhibition was used as a measure of cytotoxicity. The results clearly show an increase in the effectiveness of ADR when used along with VRP, which may be due to the changes in the cell membrane brought about by VRP.

Circulating immune complexes in chronic myeloid leukemia: studies on 37 K protein antigen.

The 37 K protein, earlier found to be present in 3.75% PEG-precipitates from sera of untreated patients with CML, was further characterized. Gel filtration at neutral pH resolved the PEG-precipitate into a non-IgG containing protein peak-I and a IgG containing peak-II. Immunoprecipitation of peak-II with antihuman IgG antiglobulin and subsequent 2D-SDS-PAGE analysis of the immunoprecipitate revealed the presence of 37 K protein in peak-II confirming its association with IgG. 125I-37 K protein was found to interact with antibodies isolated from autologous and allogenic CML-CIC samples but not with similarly isolated antibodies from normal subject, and patients with AML, ALL, MF, and HD. Peptide maps generated by tryptic digestion of 37 K protein (from five different CML patients) were found to be identical. Specific interaction of 37 K protein with the autologous and allogenic antibodies and identity of peptide maps lead to the conclusion that the 37 K protein is a CML-associated antigen appearing in CIC.

Circulating immune complexes in chronic myeloid leukemia: turbidimetric measurement and two-dimensional electrophoretic analysis.

A 3.75% polyethylene glycol -6000 mediated turbidimetric method was used for the estimation of levels of circulating immune complexes (CIC) in sera of normal human subjects and patients with chronic myeloid leukemia (CML). In terms of equivalents of heat-aggregated gamma globulin (eq.HAGG mg/ml serum), the mean levels of CIC were: 5.69 mg/ml (SD 4.78) in 81 normal human subjects; 22.63 mg/ml (SD 9.86) in 52 untreated CML patients; 7.61 mg/ml (SD 5.74) in 54 CML patients in remission; and 21.70 mg/ml (SD 8.15) in 18 CML patients in relapse. High CIC levels, thus, showed a significant association with the pretreatment -- and relapse -- status of the disease (p less than 0.001 and p less than 0.001, respectively). Though the levels decreased during remission, they were still significantly above the mean level in the controls (p less than 0.05). The CIC level-disease status relationship was clearly evident in the serial studies on 19 CML patients who donated serum samples prior to treatment as well as during remission. Two-dimensional electrophoretic analysis of the CIC samples revealed the presence of a polypeptide (mol. wt approx. 37,000 and pI approx. 5.8) in 10 out of 18 CIC samples from the untreated CML patients. Such a moiety was not detected in six CIC samples from normal subjects. The association of this polypeptide with CML gains support from the observation that in 5 CML patients, this moiety was present in the CIC samples obtained prior to treatment but absent in the samples subsequently obtained during remission.