Cardiac output and regional hemodynamics during recurrent seizures in rats.

Altered cardiovascular function in status epilepticus may contribute to mortality and morbidity in patients. We investigated changes in cardiac output and regional hemodynamics during 2 h of recurrent PTZ-induced seizures in anesthetized, paralyzed rats using radioactive microspheres, thermodilution methods, and the pulsed Doppler technique. Cardiac output fell 30-60% during recurrent seizures in 17 of 27 animals. The fall in cardiac output was sudden in onset and occurred primarily in association with seizures accompanied by prolonged increases in MABP but no change in central venous pressure. Total peripheral resistance (TPR) rose during early seizures in association with vasoconstriction of renal and certain splanchnic vascular beds. Ictal increases in TPR became attenuated during late seizures, due to failure of renal and splanchnic beds to constrict. Therefore, derangements in both cardiac and vascular function occur during late seizures. These derangements may contribute to both cerebral hypoperfusion and sudden death in status epilepticus.

Histochemical evaluation of energy metabolism in rat glioma.

The key enzymes of oxidative phosphorylation and glycolysis were evaluated histochemically in rat-implanted C6 gliomas using spot densitometry. Hexokinase, the initial enzyme for the glycolysis pathway, was 40% higher within tumour than the contralateral cerebral cortex. A similar increase within tumours for 2-deoxyglucose was observed by autoradiography. Glucose-6-phosphate dehydrogenase (G6PDH), which is the first enzyme in the pentose phosphate pathway, shunting glucose towards nucleic acid synthesis, was more than 300% higher in gliomas compared with the normal cortex. In contrast, enzymes in the energy producing tricarboxylic acid cycle (succinate-, isocitrate-, and malate-dehydrogenase) and in the electron-transport system (cytochrome c oxidase) were significantly reduced in tumour (58% less than the contralateral cortex). Lactate dehydrogenase activity, which converts pyruvate to lactate, was 50% higher within tumour. Significant reductions of enzymatic activities also occurred in non-neoplastic tissue in ipsilateral hemisphere, with larger tumours. Some enzymes showed heterogeneous activity within tumours, especially G6PDH. These results suggest that: (1) energy production is more dependent on lactate production than on oxidative phosphorylation in C6 glioma, and (2) a significant part of the increased glucose utilization in glioma cells is due to increased activity of the pentose phosphate shunt for increased DNA synthesis, and not energy production.

Tumor-associated neurological dysfunction prevented by lazaroids in rats.

The efficacy of U-74006F and U-78517F in the treatment of blood-tumor barrier permeability and tumor-associated neurological dysfunction was evaluated in a brain-tumor model in rats. U-74006F is a 21-aminosteroid and U-78517F is a 2-methylamino chroman. Rats with stereotactically implanted Walker 256 tumors were treated with methylprednisolone, U-74006F, U-78517F, or vehicle (0.05 N HCl) on Days 6 through 10 following implantation. Neurological function and vascular permeability were assessed on Day 10. Methylprednisolone and U-74006F were equally effective at preventing neurological dysfunction compared to the control group (p less than 0.01); U-78517F was slightly less effective than U-74006F and methylprednisolone but was significantly better than vehicle in preventing neurological dysfunction. Delivery of methylprednisolone resulted in a significant decrease in tumor vascular permeability (p less than 0.006) while U-74006F and U-78517F had no effect on permeability. This suggests that U-74006F and U-78517F prevented tumor-associated neurological dysfunction by a mechanism other than decreasing permeability in tumor capillaries, and that U-74006F or U-78517F could prove useful in the treatment of brain tumors.

Novel 21-aminosteroids prevent tumour associated neurological dysfunction.

The efficacy of the potent lipid peroxidation inhibitors U-74006F and U-78517F in the treatment of blood-tumour barrier permeability and tumour associated neurological dysfunction was evaluated. Rats with stereotactically implanted Walker 256 tumours were treated with methylprednisolone (MP), U-74006F, U-78517F, or vehicle. (0.05 N HCl) on days 6 through 10 following implantation. Neurologic function and vascular permeability was assessed on day 10. U-74006F and MP were equally effective at preventing neurologic dysfunction compared to control (p less than 0.01). U-78517F was slightly less effective than U-74006F and MP but was significantly better than vehicle in preventing neurological dysfunction. MP resulted in a significant decrease in tumour vascular permeability (p less than 0.006) while the lipid peroxidation inhibitors had no effect on permeability.

DMSO potentiates aminonucleoside of puromycin nephrosis in rats.

Dimethyl sulphoxide (DMSO), 3 g/kg body weight, administered daily by the intraperitoneal route, potentiated the proteinuria and formation of tubular casts in aminonucleoside of puromycin (PA) induced nephrosis in Sprague-Dawley rats. The effect was evident at 4 as well as 8-9 days following PA administration. In the absence of PA, DMSO did not induce proteinuria or cast formation. The mechanism by which DMSO enhanced proteinuria and cast formation is not known.

Mebendazole therapy of whipworm infestation: a clinical trial.

Mebendazole, a new broad-spectrum oral anthelmintic for nematodes, was given to patients harboring whipworm in a hospital for the mentally retarded. A three-day regimen (100 mg twice a day) dewormed 75% of the subjects, a five-day regimen cured 95%. The remaining patients excreted strikingly lesser amounts of the parasites' eggs after therapy. No untoward effects were noted clinically. It is the drug of choice in mixed worm infestations.

Experience with a simplification of the petroff method for laboratory diagnosis of mycobacteria in sputum.

In the original Petroff procedure sputum is digested with NaOH and the centrifuged deposit neutralized with HCl before culturing. A modification in which digestion is arrested by dilution with water and the sediment is seeded on buffered media is simpler, quicker, safer and in our hands seems to give a greater number of positive smears and cultures for mycobacteria with less overgrowth by contaminants. The usefulness of regular smear examinations for excluding tuberculosis in nonspecific chest complaints is questioned.