Inhibition of lymphocyte transformation by disrupted murine oncornavirus.

Freeze-thaw preparations of banded Rauscher murine leukemia virus markedly suppressed the in vitro cellular-mediated blastogenic response of murine splenic lymphocytes to phytohemagglutinin-P and to allogeneic cells in two-way mixed-leukocyte reaction. Suppression was shown not to be due to cytotoxicity or to virus-mitogen binding. It is suggested that a virion envelope component interferes with cellular-mediated immunity by altering cell recognition sites.     

A study of the effects of isaxonine on vincristine-induced peripheral neuropathy in man and regeneration following peripheral nerve crush in the rat.

Administration of isaxonine (6 mg/kg powdered diet) had no effect on regeneration following sciatic nerve crush in the rat. In 10 patients undergoing treatment with vincristine (1.4 mg/m2 twice monthly) development of peripheral neuropathy was quantitated by neurological symptoms, signs and electrophysiological tests. Five also received isaxonine (1.5 g daily). All patients developed evidence of neuropathy, but in none was it severe. The three lowest disability scores were obtained in isaxonine treated patients, but the highest score was also in an isaxonine treated patient. The equivocal findings in this small study could not be amplified because the drug was withdrawn from clinical use on account of its hepatotoxicity.     

Interruption of the aortic arch: experience in 17 infants

Between April, 1965, and August, 1982, 17 children ranging in age from 2 days to 4 years were identified as having interruption of the aortic arch and operated on at our institution. There were eight type A interruptions, eight type B interruptions, and one type C interruption. Associated intracardiac anomalies were present in all but 3 patients. These 3 children, who all had type A interruption, underwent repair by mobilization of the aorta and end-to-end reconstruction. The other 14 children had initial palliative operations. The 2 patients in Group 1 had type A interruption with associated ventricular septal defect (VSD), and underwent subclavian artery-aorta anastomosis. In Group 2, the palliative procedure consisted of placement of a Dacron tube graft in 1 patient with type A interruption and associated VSD, and placement of a polytetrafluoroethylene (PTFE) graft, division of the patent ductus arteriosus, and banding of the pulmonary arteries in 11 patients--2 with type A, 8 with type B, and 1 with type C interruption. Ten children (71%) survived initial palliation, 1 of the 2 in Group 1 and 9 of the 12 in Group 2. In Group 2, 5 children had interruption of the aortic arch (4, type B; 1, type C) with associated VSD; among the 4 who survived palliation, 3 subsequently have had successful closure of the VSD and 1 is awaiting closure. Among the patients who had palliative procedures, there are 6 long-term survivors (43%). In the total series, there are 9 long-term survivors (53%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of recurrent or advanced uterine sarcoma. A randomized trial of doxorubicin versus doxorubicin and cyclophosphamide (a phase III trial of the Gynecologic Oncology Group)

Recurrent or metastatic uterine sarcoma represents an ominous and aggressive form of malignant disease. In an attempt to define a beneficial treatment program, we compared treatment with doxorubicin (A) 60 mg/m2 versus a combination of doxorubicin 60 mg/m2 and cyclophosphamide 500 mg/m (CA), each regimen given every 3 weeks. Of 132 patients entered on study, 104 were eligible; 50 received A and 54 CA. Pretreatment characteristics were similar, and no patient had received prior chemotherapy. The proportion of complete responses (CR) + partial responses (PR) for measurable disease patients was 5 of 26 (19%) for both A and CA. Multivariate analysis done on progression-free interval (PFI) and survival (S) showed CA to be of no benefit over A (PFI, P = 0.22; S, P = 0.55). For both A and CA patients, measurable disease (PFI, P = 0.002; S, P = 0.02, respectively), performance status (PFI, P = 0.004; S, P = 0.0002; respectively), and sites of residual disease (PFI, P = 0.008; S, P = 0.003, respectively) were detected as prognostic variables. Conversely, histologic type, age, and recurrence status (primary versus recurrent at entry) were not prognostic indicators. These data indicate no significant benefit of CA versus A alone in patients with uterine sarcoma.     

The renal toxicity of cadmium metallothionein: Morphometric and X-ray microanalytical studies

This report describes changes in the renal lysosome system of rabbits during a tubular nephropathy produced by a single intravenous injection of cadmium metallothionein at dosages of 0, 0.1, 0.2, or 0.4 mg of Cd/kg body weight. Pronounced light microscopic and ultrastructural changes in renal tubule cells which consisted of necrosis and sloughing were observed at the highest dose. Ultrastructural morphometry and X-ray microanalysis of tubule cells were evaluated in relation to renal function and tissue cadmium levels in the same animals. The most pronounced ultrastructural change in tubule cells of treated animals at all dosages was a highly significant dose-related increase in the volume density of lysosomes which were shown by X-ray microanalysis to contain cadmium. Minor changes were observed in the volume densities of tubule cell mitochondria, nuclei, and vacuoles. The findings were associated with dose-related increases in serum creatinine concentrations and decreases in urine creatinine concentrations. The above data are discussed in relation to tissue concentrations of cadmium and the role of lysosomes in renal tubular nephropathy produced by metal-binding proteins.     

Positron Emission Tomography in the Study of Aging and Senile Dementia

¹⁸F-2-deoxy-2-fluoro-D-glucose (¹⁸FDG) is a positron emitting tracer for rate of glucose utilization in brain. When used in conjunction with positron emission tomography (PET), the PET-FDG technique permits in vivo quantitation of regional brain metabolism in man. We have applied this technique to the study of regional brain function in normal aging and senile dementia. Preliminary results for 7 patients with senile dementia of the Alzheimer's type (SDAT) and 3 elderly normal subjects indicated a large, statistically significant (p < 0.01) diminution in rate of glucose utilization in SDAT. Furthermore, the degree of diminution in metabolic activity in SDAT was highly correlated with objective measures of degree of cognitive impairment. These results demonstrate the feasibility and potential utility of the PET-FDG technique for studying regional brain function in normal aging and dementia.     

Transient toxicity of 2-deoxy-2-[18F]fluoro-D-glucose in mammalian cells: concise communication

The kinetics of uptake and toxicity of the positron emitter F-18 have been examined in a cultured cell line. 2-Deoxy-2[18F]fluoro-D-glucose (18FDG) concentrated rapidly within Chinese hamster V79 cells, and the uptake was linear with the extracellular radioactive concentrations. Whereas 18FDG synthesized 2 hr before the incubation did not appear to be toxic, that synthesized 5 hr previously was highly toxic. Toxicity was transient and independent of both the extracellular/intracellular radioactive concentration and the energy released from the decay of fluorine-18. Similarly synthesized nonradioactive FDG and Na 18F were not toxic under comparable experimental conditions. We conclude that this transient toxicity is due to an unidentified chemical species that is cytocidal following intracellular localization. These toxic levels are not likely to be achieved in the clinical use of 18FDG due to dilution factors that are orders of magnitude greater than those used in these in vitro studies.