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Biomedical subjects

B Levin

Publications and source records attributed to B Levin.

At least 37 records · Page 2Linked to original sources
PubMed1992

A pilot clinical trial of the cholecystokinin receptor antagonist MK-329 in patients with advanced pancreatic cancer.

MK-329 is a nonpeptidal, highly specific cholecystokinin (CCK) receptor antagonist, with affinity for pancreatic and gallbladder CCK receptors similar to CCK itself. MK-329 and its progenitor, asperlicin, can inhibit the growth of CCK receptor-positive human pancreatic cancer in athymic mice. Based on these activities and the ability of MK-329 to transiently increase food intake and enhance morphine analgesia in murine models, we conducted an open trial of MK-329 in 18 patients with advanced pancreatic cancer in whom the CCK receptor status of the tumors was unknown. Tumor response, pain control, and nutritional parameters (hunger rating, caloric intake, body weight, and anthropometrics) were serially assessed. The results of the study failed to demonstrate any impact of MK-329 on tumor progression, pain, or nutrition. Toxicity was mild and limited to nausea, vomiting, diarrhea, and abdominal cramps, with 17 of 18 patients able to tolerate treatment. While a role for MK-329 in the management of patients with advanced pancreatic cancer cannot be supported by the results of this trial, additional studies of this agent in patients with known CCK receptor-positive tumors, at escalated doses, and possibly in conjunction with other growth antagonists, appear warranted.

Adenocarcinoma↗
PubMed1992

Trisomy and age at menopause: predicted associations given a link with rate of oocyte atresia.

The association of trisomy with advancing maternal chronological age suggests that some aspect of physiological aging is accelerated in women with trisomic pregnancies. This paper develops a quantitative theoretical model based on the hypothesis that trisomy risk is primarily a function of the size of the oocyte pool and, in particular, that risk is increased in women with accelerated rates of oocyte atresia and hence smaller pools at given chronological ages. Since the rate of oocyte atresia is a determinant of age at menopause, this hypothesis leads to the prediction that women who have had trisomic pregnancies reach menopause earlier than women who have not. We used data relating chronological age to oocyte number, trisomy and menopause to deduce the distribution of oocyte atresia rates in all women and in women with trisomic pregnancies. Given certain simplifying assumptions, we predict that associations between trisomy and age at menopause will vary with a woman's age at the time of trisomy such that trisomies at 34-43 years will be associated with a 1-3.4 year earlier onset of menopause, while trisomies at younger or older ages will have no or little association with age at menopause. This model, while vulnerable to the uncertainties that attend its assumptions, provides a testable prediction that permits separation of one aspect of physiological age from chronological age.

Aging↗
PubMed1992

Phase II evaluation of iproplatin in patients with advanced gastric and pancreatic cancer.

A total of 48 patients with measurable advanced gastric adenocarcinoma (n = 16) or adenocarcinoma of the exocrine pancreas (n = 32) were prospectively treated with iproplatin at a starting dose of 270 mg/m2 intravenously over 2 hours. The dose was repeated every 28 days, and dose escalations or reductions were made on the basis of toxicity in the preceding course. No patient with gastric carcinoma achieved either a complete or partial response. One partial response and two complete responses were seen with pancreatic adenocarcinoma for an overall response rate of 10%. One patient has remained free of disease for more than 2 years. The major toxicities were granulocytopenia, thrombocytopenia, nausea, vomiting, and diarrhea. All toxicities were reversible upon discontinuation of the drug. On the basis of this trial, we conclude that iproplatin has no substantive activity in advanced gastric or pancreatic carcinomas.

Adenocarcinoma↗
PubMed1991

A quantitative model suggests immune memory involves the colocalization of B and Th cells.

A prominent and essential feature of the humoral immune response of vertebrates is immunologic memory: the ability to recall previous exposure to antigen. We present a mathematical model of the growth and interactions of the major cell populations involved in the humoral immune response. Our analysis of this model predicts that the formation of a dynamic association between small numbers of antigen-specific B and Th cells, "colocalization", is sufficient to account for memory and the kinetics of the secondary response--neither specifically differentiated Th or B memory cells nor networks of antigen and anti-idiotypes are required. The colocalization hypothesis explains a number of existing experimental observations and can be tested by straightforward experiments which we describe.

Animals↗
PubMed1991

Childhood obsessive-compulsive disorder and cingulate epilepsy.

There are no reports of an association between obsessive-compulsive disorder and cingulate epilepsy in childhood. We report the behavioral, cognitive, and EEG findings in a young girl with medically resistant seizures and severe obsessive-compulsive symptomatology. Her scalp EEG and neuropsychological test scores suggested right frontal lobe dysfunction. The intractability of her seizures and progressive intellectual and psychosocial deterioration prompted evaluation for excisional surgery. Intracranial EEG recording demonstrated a focal seizure origin in the right anterior cingulate gyrus. Cingulotomy resulted in freedom from seizures and significant improvement in her obsessive-compulsive symptoms.

Brain Mapping↗
PubMed1991

Resectable gastric carcinoma. An evaluation of preoperative and postoperative chemotherapy.

Patients with locoregional gastric carcinoma often die because of the low rates of curative resection and frequent appearance of distant metastases (mainly peritoneal and hepatic). To evaluate the feasibility of preoperative and postoperative chemotherapy, 25 consecutive previously untreated patients with potentially resectable locoregional gastric carcinoma received two preoperative and three postoperative courses of etoposide, 5-fluorouracil, and cisplatin (EFP). Ninety-eight courses (median, five courses; range, two to five courses) were administered. Six patients had major responses to EFP. Eighteen patients (72%) had curative resections, and three specimens (12%) contained only microscopic carcinoma. At a median follow-up of 25 months, the median survival of 25 patients was 15 months (range, 4 to 32+ months). Peritoneal carcinomatosis was the most common indication of failure. One patient died of postoperative complications, but there were no deaths due to chemotherapy. EFP-induced toxic reactions were moderate. Preoperative and postoperative chemotherapy for locoregional gastric carcinoma is feasible, and additional studies to develop regimens that could result in 5% to 10% complete pathologic responses may be warranted.

Adenocarcinoma↗
PubMed1991

p53 gene mutations in Barrett's epithelium and esophageal cancer.

Genomic DNA was extracted from archival pathology specimens comprising 10 squamous and 14 adenocarcinomas, including 7 with Barrett's epithelium adjacent to tumor, and corresponding normal esophagus from the resection margin. The polymerase chain reaction was used to amplify selected exons of p53 which were analyzed for mutations using single-strand conformation polymorphism analysis. Mutations were localized to exon 8 for 1 adenocarcinoma and to exon 5 for 1 squamous tumor and 4 of 7 Barrett's specimens. Sequencing confirmed mutations at codons 273 (CGT----CAT; adenocarcinoma) and 176 (TGC----TTC; squamous) and in Barrett's epithelium at codons 152 (CCG----CTG), 155 (ACC----GCC) and 175 (CGC----CAC). Specimens of Barrett's epithelium from separate sites had identical p53 mutations suggesting a clonal origin. Cancers arising in mutant epithelium did not have mutations corresponding to those found in the Barrett's specimens suggesting that other events are required for tumorigenesis.

Adenocarcinoma↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗