Search PubMedSearch

Biomedical subjects

B Levin

Publications and source records attributed to B Levin.

At least 55 records · Page 3Linked to original sources

A method for the quantitation of hypericin, an antiviral agent, in biological fluids by high-performance liquid chromatography.

Hypericin, a polycyclic aromatic dianthroquinone, is a natural plant product with antiviral properties. We report here the development of a methodology for the extraction and quantitation of hypericin from plasma and biological fluids and the adaptation of a sensitive and selective method for detection of the compound by high-performance liquid chromatography. The methodology offers a rapid and specific means of monitoring drug blood levels in clinical and pharmacokinetic studies. The chromatographic procedure utilizes the substantial retentive properties of hypericin on reverse-phase media and detection by the strong visible absorbance maximum at 590 nm. Verification by the fluorescence spectral properties of hypericin in organic media can also be utilized. The assay is linear over a 3 log concentration range and hypericin is consistently recovered from murine, simian, and human plasma. The methodology was applied to assess the pharmacokinetic properties of hypericin in mice receiving a single bolus injection of 350 micrograms. A distribution half-life of 2.0 h and an elimination half-life of 38.5 h were calculated. We also discuss the limitations of direct analysis of hypericin by absorbance or fluorescence measurements.

Animals

Neuroanatomic differences between dyslexic and normal readers on magnetic resonance imaging scans.

The areas of six bilateral brain segments in the right and left hemispheres, on a horizontal brain section, and the area of subdivisions of the corpus callosum, on a midsagittal brain section, were measured on magnetic resonance images obtained from 21 dyslexic and 29 control subjects. In the entire group, the frontal half of the horizontal brain section showed asymmetry, with the right side being larger, whereas posteriorly only the occipital polar segment was asymmetrical, with the left side being larger. Dyslexic subjects exhibited asymmetry, with the right side greater than the left side, in contrast to the relatively symmetrical pattern that is normally observed in the midposterior segment that corresponds to the angular gyrus. In the corpus callosum, dyslexic subjects were found to have a larger splenium than nondyslexic subjects, and dyslexic female subjects were found to have a larger splenium than dyslexic male subjects. Because transcallosal pathways connecting the left and right angular gyrus regions traverse through the splenium of the corpus callosum, the above findings in dyslexic subjects suggest an anatomic abnormality in the angular gyrus region.

Adult

Endoscopic laser recanalization is effective for prevention and treatment of obstruction in sigmoid and rectal cancer.

Patients with obstructing cancers are ineligible for preoperative chemotherapy and radiation unless they undergo surgical diversion. Endoscopic laser therapy (ELT) may provide an alternative to colostomy for these patients. We retrospectively reviewed all patients with distal sigmoid and rectal carcinomas who underwent ELT from January 1988 through April 1990. The majority of patients were referred for palliation of advanced disease. Thirty-seven patients underwent 123 ELT sessions (median, 2.5; range, one to 18). In 84% of patients, patency was maintained during a median follow-up of 31.5 weeks (range, one to 123). Morbidity and mortality were 2.5% (3/123) and 5% (1/37), respectively. Sixty-two percent had radiotherapy, chemotherapy, and/or surgery concurrent with ELT. Endoscopic laser therapy can safely and effectively reestablish and maintain luminal patency in patients with obstructing distal cancers. In addition, ELT can enable the administration of preoperative adjuvant radiotherapy and chemotherapy.

Adenocarcinoma

Phase II study of intravenous 6-thioguanine in patients with advanced gastric carcinoma.

In a phase II study, 18 patients with advanced gastric carcinoma were treated with intravenous 6-thioguanine. A 30-minute infusion of 55 mg/m2 (starting dose) was administered once a day for 5 consecutive days, the courses being repeated every 5 weeks. A median of 2 courses (range, 1-4) was administered. Among the 18 patients, 17 having measurable cancer and optimum follow-up were fully assessable for response. None of the patients achieved a complete or partial response. One patient achieved a transient minor response (15 weeks) of the primary gastric carcinoma but the metastatic carcinoma was unchanged. One patient had no change in his measurable carcinoma, and the other 15 patients had progressive disease while receiving intravenous-6-thioguanine. Myelosuppression, although frequent, was mild to moderate at these doses and did not result in significant morbidity. Nonhematologic toxicities were also mild. Our data suggest that intravenous 6-thioguanine given at this schedule is ineffective in previously untreated patients with advanced gastric carcinoma.

Adult

Phase II study of amonafide in advanced pancreatic adenocarcinoma.

To determine the efficacy of amonafide in patients with advanced, measurable pancreatic adenocarcinoma, 15 patients previously untreated with chemotherapy were entered on a phase II trial. The starting dose was 400 mg/m2 administered daily over 1 hr for 5 consecutive days repeated every 3 weeks. Because of grade 4 myelosuppression observed in the initial 2 patients, the daily starting dose was decreased to 350 mg/m2. Of the 15 patients, 14 were evaluable. Amonafide failed to produce clinical responses in the doses and schedule employed. Grade 4 granulocytopenia was observed in 3 of 9 courses at 400 mg/m2, 3 of 12 courses at 350 mg/m2 and in 1 of 4 courses at 300 mg/m2. Grade 4 thrombocytopenia was observed in 3 courses at 400 mg/m2. Nonhematologic toxicities included mild nausea and vomiting and skin rashes.

Adenine

Phase II study of intravenous 6-thioguanine in patients with advanced carcinoma of the pancreas.

In a phase II study, 32 patients with advanced pancreatic carcinoma were treated with intravenous 6-thioguanine. A 30-min infusion of 55 mg/m2 (starting dose) was administered once a day for 5 consecutive days, the course being repeated every 5 weeks. A median of two courses (range, 1-10) was administered. Among the 32 patients, 30 having measurable cancer and optimum follow-up were fully assessable for response. One patient achieved a partial response of extensive liver metastases (12+ months), and another patient had a transient minor response (5 weeks). Cancer in 27 of 30 assessable patients progressed during intravenous 6-thioguanine treatment. Myelosuppression, although frequent, was mild to moderate at these doses and did not result in significant morbidity. Nonhematologic toxicities were also mild. Our data suggest that intravenous 6-thioguanine given at this schedule is ineffective in previously untreated patients with advanced carcinoma of the pancreas.

Adult

Introduction to special issue of Cognition on lexical and conceptual semantics.

It is the fate of those who dwell at the lower employments of life, to be rather driven by the fear of evil, than attracted by the prospect of good; to be exposed to censure, without hope of praise; to be disgraced by miscarriage, or punished for neglect, where success would have been without applause, and diligence without reward. Among these unhappy mortals is the writer of dictionaries ... (Preface, Samuel Johnson's Dictionary, 1755).

Cognition

Wiping the slate clean: a lexical semantic exploration.

This paper presents a case study in lexical semantic analysis aimed at uncovering syntactically relevant components of verb meaning. Our strategy is to investigate the nature of the lexical knowledge that a speaker of English possesses with respect to certain apparently semantically related verbs: a set of verbs that might as a first approximation be classed as verbs of removal. However, a closer examination of these apparently semantically related verbs reveals that their syntactic properties diverge. An exploration of the patterns of behavior of the verbs suggests that the initial class includes three linguistically significant subclasses. The components of meaning that are relevant to characterizing each subclass are identified by isolating those components of meaning that the members of each subclass share. The conclusion considers the implications of the meaning components identified in this study for a lexical semantic representation.

Cognition

Granulocytic sarcoma of the colon.

Granulocytic sarcoma is an extramedullary tumor consisting of immature cells of the granulocytic series known to occur in patients with myelodysplastic syndrome, chronic myelogenous leukemia, or acute myelogenous leukemia. This tumor may involve nodes, cervix, bone and periosteum, and infrequently the small intestine. Granulocytic sarcoma rarely occurs in the colon and has not been previously described endoscopically. We encountered a 73-year-old man with myelodysplastic syndrome who presented with fever, diarrhea, and abdominal pain. Colonoscopic evaluation (focal ulceration, friability, and nodularity) was compatible with Crohn's disease, although histology showed a dense myeloid cell infiltrate characteristic of granulocytic sarcoma. In patients with myelodysplastic syndrome or acute or chronic myelogenous leukemia presenting with diarrhea, abdominal pain, and/or fever, colonoscopy and biopsy are indicated to determine if the colon is affected by granulocytic sarcoma.

Aged

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