Digoxin intoxication: arrhythmogenic or antiarrhythmic?
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Biomedical subjects
Publications and source records attributed to S Arvanitakis.
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OBJECTIVE: Current mortality (M(1)) in hemodynamic subgroups of patients with acute myocardial infarction (AMI) was compared to that observed 30 years ago (M(0)), when hemodynamic classification was established. The prognostic value of oxyhemodynamic indexes in predicting M(1) for patients receiving right heart catheterization (RHC) was investigated. PATIENTS AND METHODS: We assigned 393 patients with AMI (mean age, 72 +/- 10 years) to four Killip categories. A fiberoptic reflectance catheter was inserted in the pulmonary artery (PA) in 136 patients. Cardiac index (CI), PA wedge pressure (PWP), PA mixed venous blood oxygen saturation (SvO(2)), oxygen extraction ratio (O(2)ER), and normalized CI (NCI; CI/O(2)ER) were measured. Catheterized patients were classified into four Forrester groups, and M(1) and M(0) were compared. Survivors (group S) were compared to nonsurvivors (group NS), and the prognostic value of oxyhemodynamic parameters in predicting M(1) was estimated. RESULTS: A significant decline in total mortality was observed (M(1) of 8% vs M(0) of 34%; p < 0.0001). In catheterized patients, total M(1) was also decreased (M(1) of 15% vs M(0) of 26%; p < 0.05). Compared with group S, group NS had lower (mean +/- SD) CI (1.8 +/- 0.4 L/min/m(2) vs 2.4 +/- 0.6 L/min/m(2); p < 0.01), SvO(2) (46.1 +/- 10.6% vs 59.9 +/- 10.0%; p < 0.01), NCI (4.2 +/- 1.4 vs 7.4 +/- 4.1 L/min/m(2); p < 0.01), and higher PWP (22.7 +/- 6.8 mm Hg vs 14. 4 +/- 4.7 mm Hg; p < 0.01). NCI presented the best sensitivity (81%), specificity (78%), and predictive value (40%), in predicting M(1). CONCLUSIONS: The historical AMI hemodynamic classification has lost its semiquantitative value, since mortality has decreased. RHC does not compromise the outcome. NCI has a high prognostic value in predicting early mortality.
The relative frequency of the delta F508 mutation in the Greek population is 54.1%; this is similar to that reported in other Southern European populations and contrasts with the considerably higher frequencies encountered in Northern Europe and North America. The low frequency is in agreement with the linkage disequilibrium already reported between cystic fibrosis and haplotype B in this country. In contrast to the common association of pancreatic insufficiency with the homozygous delta F508 genotype, the present study revealed two homozygous children with no evidence of pancreatic failure.
The effect of plasma or serum from homozygotes and heterozygotes for the cystic fibrosis (CF) gene on the active uptake of 3-0-14C-methyl-D-glucose (3-0-14C-MDG) by rat jejunal epithelium was studied. Furthermore, the role of the polyamine, spermidine, and its products of metabolic degradation on glucose transport were investigated, and a relationship to the pathogenesis of membrane dysfunction in cystic fibrosis was postulated. Glucose transport in everted rat jejunal rings was used in the study. Results were expressed as 3-0-14C-MDG concentration ratio between the intracellular (ICF) and the extracellular fluid spaces (ECF) of the jejunal rings at the end of a 60 min incubation period. The mean ratio obtained from incubations of the rat jejunal rings in medium consisting of Krebs-Ringer-bicarbonate buffer and the labeled sugar was considered as 100% uptake. When plasma or serum, with or without spermidine, was mixed with the medium in a volume ratio of 1:3, a decrease in the active uptake of 3-0-14C-MDG was observed, expressed as percent inhibition. Percent inhibition of 3-0-14C-MDG uptake obtained when the rat jejunal rings were incubated in normal plasma was compared to that obtained with plasma from cystic fibrosis genotypes. It was found that: 1) plasma from 25 homozygous children had greater inhibitory effect on glucose uptake than plasma from 26 normal children; 2) plasma from 9 heterozygous women had greater inhibitory effect than that from 6 normal women; 3) the inhibitory effect of plasma from 3 homozygous children was not influenced by dialysis; 4) the inhibitory effects of paired plasma and serum samples from 9 homozygotes were comparable; 5) spermidine added to the incubating electrolyte solution did not affect glucose transport; 6) the addition of spermidine to reaction mixtures containing normal plasma potentiated the inhibitory effect; and 7) mixing and incubation of fresh bovine serum with reaction mixtures containing plasma from homozygotes decreased the inhibitory effect. The predominant inhibitory effect of plasma or serum from homozygotes and heterozygotes for the CF gene appears to be related to a nondialyzeable molecule(s). It does not seem to reflect the presence of high plasma glucose levels in cystic fibrosis nor to be the result of competitive inhibition between sugars. It does not seem to be the result of sodium or other electrolyte differences. A similar inhibitory effect is acquired by normal plasma after the addition of spermidine. On the other hand, plasma from CF homozygotes loses its inhibitory effect after incubation with fresh bovine serum. These findings may indicate that products of metabolic degradation of spermidine are responsible for the inhibitory effect of glucose transport and suggest the possibility of a role in abnormal polyamine metabolism in the pathogenesis of cystic fibrosis.