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Biomedical subjects

B Levin

Publications and source records attributed to B Levin.

At least 55 records · Page 3Linked to original sources

Modulating effects of calcium in animal models of colon carcinogenesis and short-term studies in subjects at increased risk for colon cancer.

A substantive amount of evidence from animal models supports the hypothesis that dietary fat is an etiological factor in colon cancer. Although various theories account for possible mechanisms, it is clear that under the influence of a basic colonic pH, fatty acids and bile acids may become highly surfactant in the colon, causing cell loss and compensatory hyperproliferation. Calcium likely reduces lipid damage in the colon by complexing with fat to form mineral-fat complexes or soaps. It has been shown in an increasing number of animal experiments that calcium has the ability to inhibit colon cancer. In limited studies in man, the colonic hyperproliferation associated with increased risk for colon cancer has been reversed for short periods by administration of supplemental dietary calcium. Taken together the available evidence suggests that increases in the daily intake of calcium in the diet may provide a means of colorectal-cancer control.

Animals

Caffeine and spontaneous abortion of known karyotype.

We tested associations of caffeine from beverages with spontaneous abortions of known karyotype. Spontaneous abortions (cases) were classified as chromosomally normal (n = 510) or chromosomally aberrant (n = 389) and, within the latter category, by type of aberration (237 trisomies, 54 monosomies X, 49 triploidies, 49 others). Controls registered for prenatal care before 22 weeks gestation and delivered at 28 weeks or later (n = 1,423). Caffeine intake in the perifertilization period did not differ among case groups and controls. For the highest category, 225+ mg/day, odds ratios (OR), adjusted for payment group and maternal age, were 1.0 for chromosomally normal cases, 0.9 for trisomies, 1.6 for monosomies X, and 0.8 for triploidies. Caffeine intake during pregnancy was tested for associations with chromosomally normal loss using the chromosomally aberrant cases to provide a robust comparison group. Although the proportion of subjects with intake of 225+ mg/day of caffeine intake in the perifertilization period does not influence the risk of chromosomally normal loss or trisomy. For monosomy X and triploidy, no strong associations were observed, but numbers were insufficient to rule out moderate effects. For caffeine intake during pregnancy, we found little evidence to support an influence on chromosomally normal loss.

Abortion, Spontaneous

Marijuana and spontaneous abortion of known karyotype.

We tested whether marijuana use in the 2 months before the last menstrual period and during pregnancy affects the risk of spontaneous abortions of known karyotype. Spontaneous abortions (cases) were defined as chromosomally normal (n = 567) or chromosomally aberrant (n = 393) and, within the latter, by type of aberration (212 trisomies, 71 monosomies X, 49 triploidies, 61 others). Controls were women with prenatal care before 22 weeks gestation and delivering at 28 weeks or later (n = 2042). In comparison with controls, adjusted odds (OR) of reported marijuana use in chromosomally normal cases were 1.1 (95% confidence interval (CI) 0.7, 1.5) and in chromosomally aberrant cases combined 1.2 (95% CI 0.7, 1.9). With respect to specific aberrations, use in the perifertilisation period did not differ significantly from that in controls for trisomies (adjusted OR = 0.8, 95% CI 0.4, 1.8), monosomies X (adjusted OR = 1.8, 95% CI 0.7, 4.3), and triploidies (adjusted OR = 1.3, 95% CI 0.4, 4.5). Comparison of karyotype groups with each other yielded similar results. Our data do not support causal associations of marijuana use, at the levels represented in our sample, with either chromosomally normal or trisomic spontaneous abortion. With monosomy X and triploidy, no statistically significant associations were detected although numbers were insufficient to rule out moderate effects.

Abortion, Spontaneous

Liver transplantation. Experience with 100 cases.

Between March 1988 and November 1989, 100 liver transplants were performed on 90 patients at Pacific Presbyterian (now California Pacific) Medical Center in San Francisco. The immunosuppressive regimen was a combination of prophylactic Minnesota antilymphocyte globulin, cyclosporine, and low-dose corticosteroids. Rejections were treated with OKT3, a monoclonal antibody, or corticosteroids. Of the 100 transplants, 32 were done on 30 children, 18 of whom weighed less than 10 kg and 9 of whom received livers that had been surgically reduced in size to fit the recipient. The overall patient survival at 2 years was 85%. Of 100 liver transplants, treatment was given for 80 (80%) for at least 1 episode of rejection. At least 1 episode of serious infection occurred in 34 of the 60 adult patients and 25 of the 30 children. Of the entire group, 2% had hepatic artery thrombosis, and 12% had biliary complications that necessitated reoperation. The quality of life has been good, with a follow-up from 1 to almost 3 years (mean = 22 months). Comparing these data with those of other published series shows a decreased incidence of surgical complications and a lower rate of fungal and viral infections. We attribute this to the reduction of steroid dosage during convalescence without jeopardizing patient or graft survival.

Adolescent

Cancer of the colon and rectum.

Colorectal cancer remains a significant medical illness and a leading cause of death in the geriatric population. Improvements in management include postoperative surgical adjuvant therapy for colonic cancer and postoperative chemotherapy and radiation for rectal cancer. Some advancement in the diagnostic and screening aspects has occurred. Management decisions in the older patients should follow the same principles as those in the younger age group, although preoperative medical evaluation is especially necessary to evaluate risk and optimize surgical, chemotherapeutic, and palliative outcomes. The best treatment for colon cancer, as for any malignancy, remains prevention. Therefore, additional efforts should focus on developing new and improved screening modalities (especially in the high-risk groups) to identify and remove premalignant lesions as well as to detect early-stage, and therefore potentially curable, large-bowel cancer.

Adenoma

Surveillance of patients with chronic ulcerative colitis. WHO Collaborating Centre for the Prevention of Colorectal Cancer.

In chronic ulcerative colitis, the object of surveillance is prevention of cancer or at least prevention of death from cancer by diagnosis at an early curable stage or by detection at a pre-malignant phase. Patients must be informed about their cancer risk as well as the limitations of endoscopic surveillance and the availability of surgical alternatives. Physicians must bear in mind the risks, benefits and costs of surveillance procedures. Patients at greatest risk of cancer for whom endoscopic surveillance is warranted are those with extensive colitis of greater than 8 years duration. Colonoscopy should be performed every 1 to 2 years at which time multiple biopsies are obtained from every 10-12 cm of normal-appearing mucosa. Targeted biopsies should also be obtained from areas where the surface appears raised as a broad-based polyp, low irregular plaque or villiform elevation, or from an unusual ulcer, particularly one with raised edges, or from a stricture. Typical inflammatory polyps need not be sampled. Colectomy is recommended in the presence of multifocal high-grade dysplasia if confirmed by an experienced pathologist. The identification of a mass lesion associated with any degree of overlying dysplasia is also a generally accepted indication for colectomy, while persistent low-grade dysplasia without a mass is somewhat more controversial. Recently introduced biomarkers may replace or supplement dysplasia in surveillance programmes as well as provide new information about malignant transformation.

Algorithms

Use of an unsaturated fatty acid auxotroph of Saccharomyces cerevisiae to modify the lipid composition and function of mitochondrial membranes.

KD115 (ol1), an unsaturated fatty acid auxotroph of S. cerevisiae, was grown in a semi-synthetic medium supplemented with 3.3 x 10(-4) M palmitoleic (cis 16:1) or palmitelaidic (trans 16:1) acids. The parent strain S288C was studied as a control. The lipid composition (fatty acids, neutral lipids, and phospholipids), respiratory activity (O2 consumption), and ultrastructure were compared in mutant yeast grown with each unsaturated fatty acid supplement. The fatty acid supplement represented 70-80% of the yeast fatty acids. Yeast grown in trans 16:1 contained more squalene, a higher ratio of phosphatidylethanolamine (PE) to phosphatidylcholine (PC), and had 10-20% of the respiratory activity compared to the same yeast grown in cis 16:1. The mitochondrial morphology of yeast in each growth supplement was notably different. The use of mixtures of cis and trans 16:1 in different proportions revealed that the PE/PC ratio, the squalene content, the respiratory defect, and the mitochondrial morphology were all similarly dependent on the fraction of trans 16:1 in the mixtures. As little as 10-20% of cis 16:1 in the mixture was sufficient to abrogate the physiological effects of trans 16:1 on each of the parameters noted above. The combined effects of high content of trans unsaturated fatty acid and the altered phospholipid composition seem to account for the decrease in lipid fluidity, the defective structure and function of the mitochondrial membrane.

Fatty Acids

Oncogene activation in esophageal cancer.

We used molecular biology techniques to study the genetic events associated with the development of human esophageal cancer. Point mutations of the p53 tumor suppressor gene were detected in one of 10 squamous cell and one of 14 adenocarcinomas of the esophagus, a frequency that implicates this gene in tumorigenesis. However, the finding of p53 mutations in Barrett's epithelium adjacent to adenocarcinomas may have clinical implications for p53 as a premalignant marker for esophageal cancer.

Adenocarcinoma

Comparison of the adaptation of acrylic resin cured by microwave energy and conventional water bath.

Acrylic resin record bases made from three commercial resins were processed by water bath curing and by microwave energy. The adaptation of the record bases to a standard cast was measured to determine if there were any statistically significant differences in the fit that could be attributed to the differences in curing methods and the brands of resin. The results indicated a small statistically significant difference in favor of the water bath cure overall, but clinically there were no appreciable differences in the adaptation of the record bases with either curing method or the resins used. The adaptation of artificial dentures made from acrylic resin is clinically acceptable with either microwave curing or the water bath method.

Acrylic Resins

A phase II trial of tamoxifen in hepatocellular carcinoma.

Because prolonged estrogen therapy can initiate hepatic adenomas, and estrogen receptors (ER) are found in 33% of hepatocellular carcinomas, a Phase II study of antiestrogen therapy was initiated in patients with hepatocellular carcinoma. Tamoxifen (20 mg twice a day) was administered to 33 patients who had biopsy proven and measurable hepatocellular carcinoma and who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. No patient had a complete or partial antitumor response; eight patients had stable disease ranging from 5 to 13 months. The median survival time for all patients was 6 months from the initiation of tamoxifen therapy. Four patients have continuing long-term survival of 18+, 22+, and 39+ months.

Adult

The unilateral wavy clavicle.

14 patients are recorded in whom one clavicle has a wavy shape not related to trauma or to a known congenital anomaly. Since the affected clavicle is more often the right, it is suggested that this alteration may be related to the effect of subclavian artery pulsations, such as cause congenial pseudarthrosis of the clavicle.

Adult

Paternal age and trisomy among spontaneous abortions.

The relationship of paternal age to specific types of trisomy and to chromosomally normal loss was investigated in data drawn from a case-control study of spontaneous abortions. Differences in paternal age between karyotype groups and controls delivering after 28 weeks gestation were tested using an urn model analysis which adjusted, by regression, for maternal age and, by stratification, for the effects of design variables (payment status, phase of study) and demographic factors (language, ethnicity). The magnitude of paternal age differences was estimated using least squares regression analysis. For chromosomally normal cases there was no association with paternal age. Among the fourteen trisomy categories examined, four (7, 9, 18, 21) showed increased paternal age (greater than or equal to 1 year above expectation), three (13, 20, 22) showed decreased paternal age and the rest, including the most common, trisomy 16, showed negligible differences. Only the association with trisomy 22 was statistically significant (P = 0.012), with a predicted reduction in paternal age of 2.1 years (95% CI -4.9, -0.5 years). This association did not vary with maternal age, payment status, phase of study, language or ethnicity. Because previous observations are extensive, the relation of paternal age to trisomy 21 was examined further. The overall association was not significant (beta = 0.8 years; 95% CI -0.8, 2.4 years). Moreover, there was evidence that the magnitude and direction of paternal age associations vary significantly within the sample, although not between subgroups defined on the basis of payment, phase of study, language or ethnicity. With respect to maternal age, the trend is towards a greater paternal age difference for trisomy 21 losses in younger women (P = 0.058). Given the number of tests performed, the finding for trisomy 22 and reduced paternal age could be due to chance. Among trisomy types, the direction of paternal age associations was not consistent for chromosomes grouped according to characteristics that might relate to the probability of nondisjunction, such as size, arm ratio, or nucleolar organizer region content, or to the potential viability of the trisomy. Thus, neither on statistical nor biological grounds do the data provide compelling evidence of paternal age effects on the trisomies found among spontaneous abortions, or on chromosomally normal losses.

Abortion, Spontaneous

Phase II study of tallysomycin S10b in patients with advanced colorectal cancer.

A total of 16 patients with histologically confirmed colorectal cancer were entered into this phase II trial, designed to evaluate the efficacy and safety of tallysomycin S10b. The compound was given i.v. weekly at a dose of 2.5 mg/m2 by push injection. Pulmonary toxicity was the most significant side effect; it was observed in three patients and required treatment discontinuation in one. Skin lesions occurred in three patients. Other side effects were mild and their relationship to drug administration was ill-defined. No responses were observed in this group of patients, most of whom had received prior therapy.

Adenocarcinoma

Evaluation of continuous-infusion alpha-difluoromethylornithine therapy for colorectal carcinoma.

A total of 32 evaluable patients with measurable advanced colorectal carcinoma were treated with continuous-infusion alpha-difluoromethylornithine (DFMO) at a median daily dose of 8 g/m2 (range, 6-14 g/m2). DFMO was infused over 24 h daily for 28 days, followed by a rest period of 7 days. Of the 32 patients, 14 had received no prior chemotherapy. A total of 65 courses was given, with the median being 2 (range, 1-9 courses). None of the patients achieved a partial or complete response; however, 3 patients achieved a minor response and 14 had stable disease. The frequent toxic effects of DFMO included thrombocytopenia (which was dose-limiting), malaise, nausea, vomiting, reversible hearing loss, and diarrhea. Our data suggest that continuous-infusion DFMO therapy is feasible and results in only mild gastrointestinal toxicity. Although DFMO proved to be ineffective as a single agent in this trial, it could probably best be used in combination with cytotoxic agents known to enhance its antitumor activity in a preclinical setting.

Carcinoma