Detergent altered alkaline phosphatase patterns of liver disease

A procedure has been described whereby the high molecular weight alkaline phosphatase (slow-moving) isoenzyme may be studied by means of polyacrylamide gel electrophoresis. By treatment of sera containing this isoenzyme with some detergents of the nonionic Triton octylphenoxyethanol series, the high molecular weight alkaline phosphatase isoenzyme is altered so that its electrophoretic mobility more closely resembles that of the usual alklaine phosphatase isoenzymes. The high molecular weight isoenzyme is thought to be associated with phosphatidyl choline and/or liproproteins. The detergent action is to dissociated the alkaline phosphatase from its lipid carrier. It is thought that these lipid-alkaline phosphatase complexes are associated with liver cell fragments. The detergent altered slow-moving alkaline phosphatase may migrate as a single band, from two to four new bands, or as several new bands. Liver, bone and intestinal alkaline phosphatase isoenzymes are unaffected by detergent action.     

Characterization of human uveal melanoma cells by phosphorus 31 nuclear magnetic resonance spectroscopy

We performed experiments to determine the potential usefulness of nuclear magnetic resonance spectra in the diagnosis and follow-up of ocular melanoma. High-resolution phosphorus 31 nuclear magnetic resonance spectra at 109.3 MHz were obtained for human uveal melanoma, Greene hamster melanoma, and normal human diploid fibroblast cells. Phosphate metabolites were identified and their concentrations were shown to vary among the different cell lines. Uveal melanoma cells contain unusually high concentrations of the phospholipid metabolite phosphorylcholine and the phosphodiesters glycerol 3-phosphoryl choline and glycerol 3-phosphoryl ethanolamine. Baseline data are thus provided for studies of the effect of various treatment modalities on uveal melanoma. These initial results suggest that the data provided by high-resolution phosphorus 31 nuclear magnetic resonance spectra can provide useful diagnostic and follow-up data with respect to ocular melanoma.     

Lessons from falling coronary heart disease mortality in the United States

The marked decline in coronary heart disease mortality in the United States since the late 1960s is most likely due in large part to successful efforts at primary prevention, attributable in turn to improved eating habits, better control of blood pressure and a reduction in smoking. Another part of the decline can probably be explained by an improvement in prognosis. It remains to be established if there has been a reduction in morbidity as well as mortality. There are other countries which have experienced declines, though of a lesser degree, while several countries have recorded increases in coronary heart disease mortality. These downward and upward turns, in general, are likewise compatible with the theory that they are caused by corresponding favourable or unfavourable changes in life styles.     

The effect of nicotine extraction filters on pulse rate and vasomotor activity: A methodological note

Smoking cigarettes through high- or low-nicotine extraction filters produced cardiovascular changes similar to those produced by smoking high- and low-nicotine cigarettes. The methodological implications of these findings are discussed.     

Morphometric measurement of tumor volume and per cent of gland involvement as predictors of pathological stage in clinical stage B prostate cancer

Although tumor volume is an important factor in predicting prognosis in carcinoma of the prostate, direct and accurate estimation of tumor volume is not practical clinically at present because the tumor may not always be palpable (stage A) and when palpable it is difficult to estimate volume in 3 dimensions. For this reason the clinical staging of prostate cancer currently is based on estimations of the per cent of gland involved with tumor: in stage A by per cent of tissue involved with cancer and in stage B by digital palpation (less than 1 lobe, 1 lobe and 2 lobes). In stage A prostate cancer the per cent of the specimen involved with tumor and the volume of tumor have been shown to correlate with tumor progression. Our study was designed to determine if either or both of these morphometric factors would be good predictors of pathological stage in stage B prostate cancer. We analyzed 56 step-sectioned radical prostatectomy specimens: 28 without capsular penetration, 15 with capsular penetration only and 13 with seminal vesicle involvement. The per cent of gland involved with tumor (correlation coefficient 0.67, p less than 0.001) and tumor volume (correlation coefficient 0.55, p less than 0.001) correlated well with pathological stage. Stepwise linear regression showed that the combination of the per cent of gland involved with tumor and the total Gleason grade was statistically the best predictor of pathological stage.     

High-dose combination alkylating agent therapy with autologous bone marrow rescue for refractory solid tumors

Twenty-six adults, ages 27 to 60, with refractory metastatic solid tumors were treated with high-dose cyclophosphamide (Cy) + carmustine (BCNU) at one of three escalating dose schedules followed by autologous bone marrow transplantation (ABMT). Toxicity was severe and dose-related, with the maximum tolerated dose for the combination determined to be Cy 160 mg/kg and BCNU 900 mg/m2. Median time to WBC recovery (greater than or equal to 1,000/microL) was 13 days post-ABMT (range, nine to 22 days) and to a platelet count of greater than or equal to 50,000/microL, 22 days (range, 13 to 83 days). Sixteen of 20 evaluable patients (80%) responded to therapy with at least 50% reduction in measurable tumor, and three patients achieved complete remission (CR). Responders included eight of nine evaluable patients with breast carcinoma, two of five with melanoma, two of two with sarcoma, and four of four with colon carcinoma. Response durations were short (median, 4 months), even for complete responders, and relapses generally occurred at sites of previous metastases. In order for this approach to have a more significant impact on overall survival, it may need to be applied earlier in the natural history of the malignancy.     

Trabecular precipitates and elevated intraocular pressure following argon laser trabeculoplasty

Two patients with pseudoexfoliation glaucoma underwent argon laser trabeculoplasty for control of intraocular pressure. Within 1 month both patients developed elevated intraocular pressure associated with many large inflammatory precipitates on the trabecular meshwork detected only by gonioscopy. Treatment with topical steroids for 7 to 10 days resolved these precipitates and lowered the intraocular pressure. We believe our patients had severe trabeculitis occurring as a late reaction to argon laser trabeculoplasty. An increase in intraocular pressure following trabeculoplasty warrants careful gonioscopic examination; in fact we recommend routine gonioscopy for all patients after laser treatment.     

The effect of donor-specific blood transfusion, cyclosporine, and dietary prostaglandin precursors on rat cardiac allograft survival. II. Effectiveness of a 24-hour induction period with DST and CsA in inducing long-term graft survival

We investigated the effect of donor-specific transfusion given 24 hours pretransplant, a short course of low-dose cyclosporine, and dietary enrichment with the prostaglandin precursor linoleic acid (LA) to see which of the modalities could act synergistically on cardiac allograft survival in a stringent animal model. ACI male rats (RT1a) were used as blood and heart donors, and Lewis male rats (RT1l) were used as recipients. DST alone (1 ml) given 24 hr pretransplant or LA alone started 24 hr pretransplant and given daily p.o. until rejection prolonged cardiac allograft survival slightly but significantly, from 6 to 8 days. CsA alone started at the time of transplant at a dose of 5 mg/kg/day s.c. and given daily for 14 days prolonged cardiac survival to 11.8 days. However, when CsA was started 24 hr pretransplant and continued for two weeks, there was a significantly prolonged allograft survival to 55 days. CsA given together with DST 24 hr pretransplant and continued for two weeks posttransplant significantly prolonged cardiac allograft survival to 80 days and resulted in permanent tolerance in some animals. The addition of LA to a DST and CSA treatment regimen did not further improve allograft survival. CsA blood levels were determined in a separate group of Lewis rats. Three dosages of CsA were administered s.c. for 2 weeks: 2.5 mg/kg/day, 5 mg/kg/day, and 10 mg/kg/day. One injection of the three CsA doses did not achieve what are considered therapeutic levels in man. After 5 days, all three doses of CsA achieved significant blood levels. Significant blood levels were still present one week, but not 3 weeks after CsA was stopped. We conclude that DST given 24 hr before transplant and a 2-week course of low-dose CsA started one day pretransplant have strong synergism in inducing long-term graft survival in this rat model. Linoleic acid started 24 hr pretransplant, together with DST and CsA, did not contribute significantly to graft survival compared with the group given CsA and DST alone. Prolonged heart allograft survival was not due to persistently high CsA levels after the drug was discontinued.