Cardiac autonomic dysfunction in survivors of acute lymphoblastic leukemia in childhood

Lower levels of baseline ventilatory function have consistently been associated with increased risk of cardiovascular mortality in prospective studies, but the underlying mechanisms are not known. Increased risk of coronary heart disease is associated with higher serum insulin levels. This report examines the relationship between ventilatory function and indirect measures of insulin resistance. Cross-sectional data from 922 nondiabetic participants in the Normative Aging Study were analysed using multiple linear regression models with adjustment for potential confounders. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were examined in relation to indicators of insulin resistance, i.e. fasting insulin and the fasting insulin resistance index (FIRI). Diabetics were excluded because impaired insulin secretion interferes with the validity of these as measures of insulin resistance. Fasting insulin and FIRI were negatively correlated with FVC and FEV1 (all p< 0.001). These associations persisted after adjusting for potential confounders including age, height, body mass index, waist to hip circumference ratio, physical activity, alcohol intake and smoking in separate multiple linear regression models, for both insulin (all p< or =0.0008) and FIRI (all p< or =0.0001). Negative cross-sectional associations between ventilatory function and indirect measures of insulin resistance were found in nondiabetic males. Insulin resistance may contribute to the previously unexplained association between ventilatory function impairment and cardiovascular mortality. Mechanisms underlying the relationship between insulin resistance and decreased ventilatory function remain to be elucidated.     

Long-term follow-up after subtotal parathyroidectomy in patients with renal failure

OBJECTIVES/HYPOTHESIS: The most appropriate type of surgery for hyperparathyroidism secondary to renal failure remains controversial. We report a 5-year experience of patients with hyperparathyroidism secondary to end-stage renal disease who underwent subtotal parathyroidectomy. We believe that this is the procedure of choice, offering several advantages over total parathyroidectomy with and without reimplantation. STUDY DESIGN: Retrospective review. METHODS: Review of 14 consecutive renal failure patients who underwent subtotal parathyroidectomy by one surgeon (A.K.) was performed. Follow-up ranged from 4 to 54 months. All patients were receiving chronic maintenance dialysis. All patients came to surgery with clinical symptoms of parathyroid bone disease, elevated serum calcium levels (10.1-12.4 mg/dL), and intact parathyroid hormone levels (619-4160 pg/mL), despite maximal medical therapy. At exploration four glands were identified in all patients and three and a half were removed. RESULTS: All patients experienced symptomatic relief postoperatively with normalization or near-normalization of serum calcium concentration and intact parathyroid hormone concentrations. One patient developed recurrent disease 4 months after surgery, and on re-exploration a supernumerary substernal gland was identified. A second patient developed recurrent symptoms 4 years after surgery and at the time of this writing was awaiting re-exploration. CONCLUSIONS: All patients had either resolution of or marked improvement in their subjective complaints. There have been no cases of permanent hypoparathyroidism. We believe that subtotal parathyroidectomy is the best procedure for patients with refractory symptoms of secondary hyperparathyroidism.     

The contribution of noncatalytic phosphate-binding subsites to the mechanism of bovine pancreatic ribonuclease A

The enzymatic catalysis of polymeric substrates such as proteins, polysaccharides or nucleic acids requires precise alignment between the enzyme and the substrate regions flanking the region occupying the active site. In the case of ribonucleases, enzyme-substrate binding may be directed by electrostatic interactions between the phosphate groups of the RNA molecule and basic amino acid residues on the enzyme. Specific interactions between the nitrogenated bases and particular amino acids in the active site or adjacent positions may also take place. The substrate-binding subsites of ribonuclease A have been characterized by structural and kinetic studies. In addition to the active site (p1), the role of other noncatalytic phosphate-binding subsites in the correct alignment of the polymeric substrate has been proposed. p2 and p0 have been described as phosphate-binding subsites that bind the phosphate group adjacent to the 3' side and 5' side, respectively, of the phosphate in the active site. In both cases, basic amino acids (Lys-7 and Arg-10 in p2, and Lys-66 in p0) are involved in binding. However, these binding sites play different roles in the catalytic process of ribonuclease A. The electrostatic interactions in p2 are important both in catalysis and in the endonuclease activity of the enzyme, whilst the p0 electrostatic interaction contributes only to binding of the RNA.     

Selective loss of [3H]kainic acid and [3H]AMPA binding in layer VI of frontal cortex in Huntington's disease

Excitatory amino acid neurotoxicity has been proposed to cause the neostriatal neuronal degeneration of Huntington's disease (HD); N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and kainate receptors have been hypothesized to play important roles in this process. We have recently reported a loss of neurons in layer VI of the cerebral cortex in HD. Using quantitative autoradiographic methods, we have now measured NMDA, AMPA, and kainate receptor binding in the frontal cerebral cortex of the brains of controls and individuals with HD. We find no change in NMDA receptor binding but a selective decrease in kainate and AMPA receptor binding in layer VI. These data suggest that cerebral cortical neurons possessing kainate or AMPA receptors may be selectively vulnerable in individuals with HD.     

Action of pure ethanol and some alcoholic beverages on the gastric mucosa in healthy humans: a descriptive endoscopic study

A method for the simultaneous determination of residues of 17 beta-trenbolone and 17 beta, 19-nortestosterone and their epimers in animal tissues is described, involving immunoaffinity chromatography clean-up and high-performance liquid chromatography with dual-wavelength UV detection. The method has been validated at 2 micrograms/kg in pig and cattle liver and corned beef with recoveries of 41% upwards. The method has been applied to the determination of incurred residues of 19-nortestosterone and trenbolone. Various alternative extraction steps for incurred trenbolone have been investigated, including direct extraction, protease digestion, heating and ultrasonic probe treatment. Glucuronidase digestion has been shown to be the most effective method for this analyte.     

Extragenital donovanosis of the foot

Kartagener's syndrome (KS) usually includes mirror-image dextrocardia. The incidence of congenital heart disease in KS is comparable with that in the general population. This paper reports on a case of Kartagener's syndrome associated with dextrocardia, corrected transposition of the great arteries (I,D,D), ventricular septal defect, and valvar pulmonary stenosis in an 8-year-old girl.