Methotrexate (MTX) plus ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis

This placebo-controlled, randomized, multicenter trial compared the effects of MTX plus UDCA to UDCA alone on the course of primary biliary cirrhosis (PBC). Two hundred and sixty five AMA positive patients without ascites, variceal bleeding, or encephalopathy; a serum bilirubin less than 3 mg/dL; serum albumin 3 g/dL or greater, who had taken UDCA 15 mg/kg daily for at least 6 months, were stratified by Ludwig's histological staging and then randomized to MTX 15 mg/m2 body surface area (maximum dose 20 mg) once a week while continuing on UDCA. The median time from randomization to closure of the study was 7.6 years (range: 4.6-8.8 years). Treatment failure was defined as death without liver transplantation; transplantation; variceal bleeding; development of ascites, encephalopathy, or varices; a doubling of serum bilirubin to 2.5 mg/dL or greater; a fall in serum albumin to 2.5 g/dL or less; histological progression by at least two stages or to cirrhosis. Patients were continued on treatment despite failure of treatment, unless transplantation ensued, drug toxicity necessitated withdrawal, or the patient developed a cancer. There were no significant differences in these parameters nor to the time of development of treatment failures observed for patients taking UDCA plus MTX, or UDCA plus placebo. The trial was conducted with a stopping rule, and was stopped early by the National Institutes of Health at the advice of our Data Safety Monitoring Board for reasons of futility. In conclusion, methotrexate when added to UDCA for a median period of 7.6 years had no effect on the course of PBC treated with UDCA alone.     

Comparison of creatine kinase elevation and outcome of comparison of percutaneous coronary intervention for saphenous vein graft in-stent restenosis versus de novo stenosis

Percutaneous coronary intervention of saphenous vein grafts is associated with distal embolization. We aimed to compare potential differences in patients undergoing percutaneous coronary intervention for in-stent restenosis with de novo saphenous vein graft lesions. Myocardial necrosis was associated with higher mortality regardless of lesion type.     

Induction of congenital hydrocephalus with mumps virus in rhesus monkeys.

Rhesus monkey fetuses were inoculated intracerebrally with wild-type mumps virus near the beginning of the last third of the gestation period. Within three days after inoculation, mumps virus was isolated from many fetal tissues. Thirteen animals receiving virus were delivered at term. Five of these showed slight to severe hydrocephalus. Hydrocephalus was most prominent in the posterior horns of the lateral ventricles, but other lesions occurred at various levels of the ventricular system. Virus was isolated from three animals at one day of age (two months after inoculation). However, mumps virus was not recovered from one-month-old monkeys. The recovery of mumps virus from newborn rhesus monkeys two months after inoculation suggests that attempts should be made to document similar persistence of the virus in humans. Furthermore, this model indicates that mumps virus infection in humans may result in hydrocephalus.     

Myocardial salvage after failed coronary angioplasty

Patients undergoing coronary angioplasty have a 2% to 7% risk of requiring emergency coronary artery bypass graft surgery for impending infarction. These patients provide a unique model of early reperfusion because the exact time of compromise to blood flow and the composition of the reperfusion solution are known. However, the amount of myocardium salvaged is unknown. Between December 1981 and September 1985, 859 patients underwent coronary angioplasty. Forty-two patients had emergency surgery for objective evidence of impending infarction. Five patients died. Thirty-six patients were contacted for follow-up; 21 (58%) of 36 had a radionuclide ventriculogram performed at a mean of 39 +/- 13 months after surgery. These radionuclide studies were compared with the patient's preangioplasty contrast ventriculogram. One patient had a myocardial infarction 3 years after surgery. Eleven (55%) of the remaining 20 patients had a normal radionuclide ventriculogram at follow-up study (ejection fraction 65 +/- 9%). Five (25%) of the 20 patients had a depressed ejection fraction (46 +/- 4%) with wall motion abnormalities, but these were unchanged from the preangioplasty studies. Four patients (20%) had a significant decrease in ejection fraction over baseline (37 +/- 10%) with new wall motion abnormalities. In conclusion: 1) there is an 80% chance that left ventricular function will be unchanged at 3 year follow-up study in patients surviving emergency bypass grafting for failed angioplasty; 2) these data suggest that early revascularization for impending infarction in this setting is associated with a good late outcome; and 3) this patient group offers a unique opportunity to study the effects of early reperfusion in a human model.     

Percutaneous transluminal coronary angioplasty (PTCA) in the elderly patient: Experience in the national heart, lung, and blood institute PTCA registry

Because CABG results in a significantly higher morbidity and prolonged hospitalization in the older patient group, PTCA is an attractive alternative for providing myocardial revascularization in the small group of older patients with appropriate lesions for dilation. This analysis of the results of PTCA in 370. older patients in the NHLBI PTCA Registry reveals that PTCA can be performed with acceptably low mortality and morbidity. Therefore, PTCA may offer an alternative to CABG in the highly selected symptomatic older patient.     

Peroxidase-H2O2-halide system: Cytotoxic effect on mammalian tumor cells

Myeloperoxidase, H2O2, and a halide constitute a potent antimicrobial system. A cytotoxic effect of this system on a line of mouse ascitic lymphoma cells (LSTRA) is demonstrated here using four different assay systems: 51Cr release, trypan blue exclusion, inhibition of glucose C-1 oxidation, and loss of oncogenicity for mice. Deletion of each component of the system, preheating the peroxidase, or addition of azide, cyanide, or catalase abolished the cytotoxicity. Myeloperoxidase was effective with either chloride or iodide as the halide, while lastoperoxidase was effective with iodide but not chloride. The iodinated thyroid hormones, triiodothyronine and thyroxine, could substitute for the halide, and H2O2 could be replaced by a peroxide- generating enzyme system such as glucose and glucose oxidase or by H2O2 producing bacteria such as pneumococci or streptococci. The possibility is raised that the peroxidases of inflammatory cells and certain biologic fluids may affect tumor initiation or growth in vivo.