Hereditary Hemolytic Disease Secondary to Glucose-6-Phosphate Dehydrogenase Deficiency: Report of Three Cases with Special Emphasis on ATP Metabolism

1. Three cases of hereditary hemolytic disease secondary to G-6-PD deficiency are described. Two of the cases were first cousins of Scotch-Irish-English descent and the mode of inheritance was believed to be sex-linked.The third case was of Turkish origin; no family studies were availale.

2. The mothers, who were heterozygous for G-6-PD deficiency, showed onlyminimal expression of the defect, which was manifested by a slightly decreasedred cell survival in both mothers and an abnormal methemoglobin reductiontest in one of them.

3. All three cases showed a more pronounced fall in erythrocyte ATP afterincubation with phenylhydrazine than that observed in primaquine-sensitiveNegroes whose red cells were less deficient in G-6-PD.

4. It is suggested that the inability of the G-6-PD-deficient erythrocyte tomaintain adequate levels of ATP may be an important factor in the pathogenesis of the hemolytic process.

Submitted on August 26, 1963 Accepted on October 24, 1963     

The pulmonary bioprosthetic heart valve: its unsuitability for use as an aortic valve replacement

BACKGROUND AND AIM OF THE STUDY: The porcine pulmonary bioprosthetic heart valve represents an alternative means of aortic valve replacement (AVR), though knowledge of its biomechanical function and characteristics is limited. The valve has potential advantages over the aortic bioprosthesis; notably, it lacks the muscular shelf of the right coronary cusp of the latter bioprosthesis. The study aim was to investigate the suitability of the porcine pulmonary bioprosthetic valve for AVR. METHODS: Porcine pulmonary and aortic roots were zero pressure-fixed with 0.5% buffered glutaraldehyde, characterized, and compared with fresh porcine pulmonary and aortic roots. The in-vitro analysis included assessment of mechanical properties, hydrodynamic function, geometry of the pulmonary root, and durability. RESULTS: The fixed pulmonary roots and fresh aortic roots were similar in certain aspects of mechanical response, notably leaflets in the radial direction and the root wall. The fixed pulmonary root was slightly more compliant than the fixed aortic root, and this led to an improvement in forward flow hydrodynamic function. The reverse flow hydrodynamic function of the pulmonary roots was poor; fresh pulmonary roots exhibited a trivial closed valve regurgitant volume. On fixation, this characteristic was aggravated, leading to a gross closed valve regurgitant volume in 50% of all fixed pulmonary roots. The cause of leakage was identified as a prolapsed anterior leaflet. Durability of the fixed pulmonary root was also inferior to that of the fixed aortic root; three fixed pulmonary roots subjected to accelerated fatigue testing showed signs of leaflet macroscopic damage. CONCLUSION: Overall, the performance of the porcine pulmonary bioprosthesis was far inferior to that of the currently used porcine aortic bioprosthesis. Hence, the porcine pulmonary bioprosthetic valve was deemed unsuitable for AVR.     

Brown adipose tissue in patients with phaeochromocytoma

Intra-abdominal adipose tissue was obtained at laparotomy from three subjects with high circulating noradrenaline concentrations in the presence of phaeochromocytoma. Light and electron microscopy confirmed typical brown adipose tissue, both adjacent to, and in one case distant from, the tumour. Biochemically, in terms of high cytochrome-C oxidase activity, mitochondrial GDP-binding, GDP-inhibitable uncoupled mitochondrial respiration, and specific concentration of uncoupling protein (mean 31 +/- 7 micrograms/mg mitochondrial protein) the tissue possessed all the unique features of thermogenically active brown adipose tissue. These findings are contrasted with low results obtained from a case with Cushing's disease, and the significantly lower results (mean 2.5 +/- 1.8 micrograms/mg) in a group of control adults (P less than 0.02). In the presence of high circulating noradrenaline concentrations, the intra-abdominal fat of human adults, including the omental fat, which is brown adipose tissue in infancy, becomes reactivated and may be contributing to the weight loss which is typically seen with phaeochromocytoma. Human adult brown adipose tissue thus has the biochemical potential for the thermogenic activity required in order to contribute to the regulation of energy balance and body weight.     

Increased sympathetic nervous activity and the effects of its inhibition with clonidine in alcoholic cirrhosis.

OBJECTIVE: To study disturbances in sympathetic nervous system function in patients with alcoholic cirrhosis and the effect of clonidine on such disturbances. DESIGN: Cross-sectional physiologic and neurochemical evaluation of patients with cirrhosis and of healthy controls; an uncontrolled trial of intravenous clonidine in the cirrhotic patients. PATIENTS: Forty-four hospitalized patients with biopsy-proven alcoholic cirrhosis and 31 healthy controls. INTERVENTIONS: Intravenous clonidine. MAIN OUTCOME MEASURES: Radiotracer-derived measures of norepinephrine release to plasma, central hemodynamics, wedge hepatic vein pressure, and measures of renal function. MAIN RESULTS: In patients with cirrhosis, clonidine reduced previously elevated norepinephrine overflow rates for the whole body, kidneys, and hepatomesenteric circulation. This sympathetic inhibition was accompanied by the following potentially clinically beneficial effects: the lowering of renal vascular resistance (median reduction, 24%; 95% CI, 14% to 31%), the elevation of glomerular filtration rate (median increase, 27%; CI, 14% to 39%), and the reduction of portal venous pressure (median reduction, 25%; CI, 18% to 32%). The norepinephrine and hemodynamic responses to graded clonidine dosing (1, 2, and 3 micrograms/kg body weight intravenously) indicated that the sympathetic outflow to the hepatomesenteric circulation was more sensitive to pharmacologic suppression with clonidine than was the sympathetic outflow to the systemic circulation. CONCLUSIONS: The sympathetic nerves to the kidneys, heart, and hepatomesenteric circulation are stimulated in patients with cirrhosis. Clonidine inhibits these activated sympathetic outflows differentially, which could possibly provide a basis for the selective pharmacologic treatment of portal hypertension in patients with cirrhosis.     

Suppression of ongoing experimental allergic encephalomyelitis in DA rats by novel peptide drug,structural part of human myelin basic protein 46–62

Previously, we demonstrated that autoantibodies (AAb) in multiple sclerosis (MS) reveal site-specific binding and cleavage toward myelin basic protein (MBP) epitope library. We have found several fragments of MBP immunodominant in terms of AAb binding. Here, we applied these peptides to DA rats with induced protracted relapsing experimental allergic encephalomyelitis (EAE) most closely related to MS. DA rats with EAE induced by syngenic spinal cord homogenate in complete Freund's adjuvant were treated by nasal route with human MBP 46–62, 81–102, 124–139, 147–170, and Copaxone®. MBP 124–139 and 147–170 displayed only mild therapeutic effects but MBP 46–62 significantly reduced EAE, reflected by lower clinical scores and shorter EAE duration compared to controls.