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Biomedical subjects

B Levin

Publications and source records attributed to B Levin.

At least 109 records · Page 6Linked to original sources
PubMed1996

Cell kinetic analysis of intact rat colonic crypts by confocal microscopy and immunofluorescence.

BACKGROUND & AIMS: Precise quantitative and spatial analysis of cell cycle-related biomarkers in colonic crypts is often vital for studies of colon carcinogenesis and cancer prevention. To overcome the limitations of histology, confocal laser microscopy of microdissected whole crypts was used to quantitate S phase and mitotic cells. METHODS: Microdissected distal colonic crypts were studied in a modified rat starvation refeeding model. S phase cells were labeled in vivo with 5-bromodeoxyuridine. Mitotic cells were labeled with MPM2 (antibody to mitosis-specific epitope) and also assessed for chromatin morphology with propidium iodide. Sequential optical crypt sections, produced by confocal microscopy, were digitally imaged. S phase labeling indices per whole crypt were also compared with those derived by conventional immunohistochemistry. RESULTS: S phase and mitotic cells were clearly discriminated without background staining. The labeled S phase cell number and fraction per whole crypt were significantly decreased with starvation and increased with refeeding. Variability in the labeling index between whole crypts analyzed by confocal microscopy was significantly smaller than between histological crypt sections. Consequently, the intervention contributed to 92.2% of the total variability of the labeling index in whole crypts but only to 59% of the variability in histological sections. CONCLUSIONS: Major limitations of histology are overcome by crypt microdissection and confocal microscopic analysis. The total crypt cell population as well as labeled M phase and S phase cells can be imaged, localized, and quantitated with improved precision.

Animals↗
PubMed1996

Mutations of p53 in Barrett's esophagus and Barrett's cancer: a prospective study of ninety-eight cases.

We had previously identified p53 mutations in Barrett's esophagus and therefore began a multiinstitutional study to determine their significance as a marker for malignancy. Ninety-eight patients from four institutions were studied. Forty-eight patients (37 men and 11 women, mean age 56.2 years) had Barrett's esophagus with metaplasia or dysplasia but no evidence of malignancy at a mean follow-up of 2.2 years. Barrett's esophagus was classified as metaplasia with no evidence of dysplasia in 32 patients, as low-grade dysplasia in 13, and as high-grade dysplasia in three. The other 50 patients (46 men and four women, mean age 60.2 years) had adenocarcinoma arising in Barrett's esophagus. Tissues from normal stomach or esophagus, tumor, and Barrett's esophagus were obtained for deoxyribonucleic acid analysis by endoscopic biopsy from patients with Barrett's esophagus or cancer or during operations on some patients with Barrett's cancer. Exons 5 through 9 of the p53 gene were studied for mutations by single-strand conformational polymorphism analysis after polymerase chain reaction amplification. Mutations detected by single-strand conformational polymorphism analysis were confirmed by deoxyribonucleic acid sequencing. None of the tissue samples from patients with Barrett's esophagus alone and no dysplasia or low-grade dysplasia had any p53 mutations, but one of the three patients with high-grade dysplasia and no evidence of invasive malignancy did have a p53 mutation. Of the 50 patients with Barrett's cancer, however, 23 (46%) had p53 mutations in Barrett's epithelium, tumors, or both. Twenty of these patients had p53 mutations in the tumor only (n = 16) or in both tumor and Barrett's epithelium (n = 4), suggesting that the mutation plays a direct role in carcinogenesis. Mutations in Barrett's epithelium were found in one patient in the group without malignancy and in seven patients with cancer (one with no dysplasia, two with low-grade dysplasia, and five with high-grade dysplasia). In three patients with cancer, mutations occurred only in Barrett's epithelium, suggesting that such mutations may also be a marker for genomic instability. Mutations were predominantly found in exons 5, 7, and 8, and transitions from guanine to adenine were the most frequent changes. Mutations of p53 are clearly involved in the pathogenesis of Barrett's cancer for a subset of patients (46%), and the fact that we could detect mutations in premalignant Barrett's epithelium supports the hypothesis that p53 mutations may be a useful marker for patients at increased risk for development of invasive cancer.

Adenocarcinoma↗
PubMed1996

Association of diet and colorectal adenomatous polyps: dietary fiber, calcium, and total fat.

We conducted a case-control study to investigate the relation between dietary fiber, calcium, and total fat and the risk of colorectal adenomatous polyps. We used a food frequency questionnaire to assess the usual diet for 157 cases and 480 controls. In multivariate analyses, dietary fiber was inversely associated with risk of adenomatous polyps. The odds ratio (OR) for individuals in the highest vs the lowest quartile was 0.5 [95% confidence interval (CI) = 0.3-0.9]. We found an inverse association between dietary calcium and risk of adenomatous polyps, but the protective effect was present only for individuals in the fourth vs the first quartile (OR = 0.7; 95% CI = 0.3-1.3). Intake of total fat was positively associated with risk of adenomatous polyps, but we saw no consistent trend. Calcium intake appeared to modify the effect of total fat intake on the risk of adenomatous polyps.

Adenomatous Polyps↗
PubMed1996

Preoperative clinical, EEG, and imaging findings do not predict seizure outcome following temporal lobectomy in childhood.

Although certain clinical, electroencephalographic (EEG), magnetic resonance imaging (MRI), and pathologic findings in adults with intractable temporal lobe epilepsy predict seizure outcome following temporal lobectomy, predictors of seizure outcome have not been studied systematically in pediatric temporal lobectomy series. We retrospectively analyzed preoperative clinical, EEG, and neuroimaging findings with reference to seizure outcome (seizure free or non-seizure free) in 33 children (mean age, 9.3 years) who underwent tailored temporal lobe resections for intractable temporal lobe epilepsy. Trends were apparent with (1) younger age at seizure onset, younger age at surgery, shorter duration of epilepsy, localized unilateral temporal lesions on MRI, and right-sided surgery more frequently associated with a seizure-free outcome, and (2) significant prior history, daily preoperative seizures, generalized motor seizures, mental retardation, and localized unilateral temporal epileptiform EEG activity more frequently associated with a non-seizure-free outcome. However, none of these findings, alone or in combination, correlated with postoperative seizure status at a statistically significant level. Submitting the four variables generally considered to be most predictive of favorable outcome (ie, normal intelligence, unilateral ictal and interictal EEG discharges, and focal temporal MRI lesion) to a multiple-cutoff procedure did not predict seizure freedom. Our data indicate that predictors of outcome of temporal lobectomy in adults may not apply in children, perhaps due to inherent neurobiologic differences in the etiology and expression of temporal lobe epilepsy, and should therefore not be used as sole determinants of surgical candidacy in children.

Adolescent↗
PubMed1996

Screening for Colorectal Cancer.

Colorectal cancer is a major cause of morbidity and mortality in the United States. Early detection of the disease at an asymptomatic stage by screening holds promise for lowering the incidence of colorectal cancer deaths, yet compliance with screening guidelines is poor. Evidence in support of the use of screening techniques for colorectal cancer is accumulating, however, and screening for this disease with fecal occult blood tests and flexible sigmoidoscopy can increase the likelihood of early detection, can decrease mortality and morbidity, and can be cost effective.

Journal Article↗
PubMed1996

Factors associated with emergency department visits by children with asthma: implications for health education.

OBJECTIVES: This study investigated the relationship between psychosocial and behavioral factors and the frequency of emergency department visits for childhood asthma. METHODS: Data obtained from a survey of parents of 445 children who were being treated for asthma in the emergency room of a large urban hospital were examined. RESULTS: Factors associated with high emergency department use included the child's being of younger age, a greater number of days with symptoms of asthma, a higher number of asthma medicines prescribed, a prior hospitalization for asthma, a lower level of parental confidence in the efficacy of medicines, and a failure to use a criterion for deciding to seek emergency care. CONCLUSIONS: Younger children with asthma and children with previous hospitalization for asthma are at high risk for using emergency care. Families who use the emergency department frequently need to be further educated in the inflammatory nature of the disease, in the efficacy of proper use of medicine, in the need for ongoing care, and in criteria to distinguish those symptoms that can be handled at home from those requiring emergency care.

Age Factors↗
PubMed1996

Clinical and prophylactic trials with assured new treatment for those at greater risk: I. A design proposal.

OBJECTIVES: The accepted sine qua non for estimating the difference in efficacy between a new and a standard treatment is a randomized controlled clinical trial. Yet in some situations it is either practically or ethically impossible to conduct such a trial. For example, patients who are desperately ill may decline to participate when they learn they may not receive the new treatment, especially when that treatment is readily available outside the experimental protocol. Likewise, in a prophylactic trial of a promising vaccine, recruitment of persons at greater risk may falter or fail. Our objective is to demonstrate that a rigorous comparison of treatments may still be attainable. METHODS: The features of a controlled clinical or prophylactic trial are reviewed from the perspectives of Food and Drug Administration regulations, ethical considerations, and practical problems. RESULTS: An explicit risk-based allocation method of design and analysis is proposed, one guaranteeing that all subjects at greater risk will receive the new treatment. CONCLUSIONS: Under certain conditions, a risk-based allocation trial can furnish consistent estimates of both standard and experimental treatment effects for those at greater risk while avoiding certain difficulties caused by randomized treatment allocation.

Control Groups↗
PubMed1996

Clinical and prophylactic trials with assured new treatment for those at greater risk: II. Examples.

OBJECTIVES: The preceding article proposed an assured treatment design that would address certain difficulties in recruiting persons who are at greater risk into randomized clinical trials. The purpose of this article is to illustrate the statistical validity of the design in a practical setting. METHODS: Three actual randomized clinical trials were considered as case studies; in each, the data that would have been obtained under assured allocation were identified. Then, with only these data, together with a reasonable choice of model describing the response of subjects under standard treatment as a function of initial severity, the treatment effect was estimated for the subjects at greater risk. The estimates were compared with conventional estimates for the sicker patients randomized in the original trials. RESULTS: In each case, the estimates produced in the assured treatment trial were close to those observed in the randomized trial. CONCLUSIONS: Risk-based allocation trials deserve serious consideration when randomized clinical trials are difficult or impossible to execute. The proposed designs and analyses would allow physicians to offer persons at greater risk assurance that they would receive the new treatment, while researchers would retain the ability to draw valid statistical conclusions about treatment efficacy.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Treatment for breast cancer and blood levels of chlorinated hydrocarbons.

Small studies have examined, with conflicting results, whether breast cancer risk is increased among women exposed to high levels of chlorinated hydrocarbons, as measured in breast fat tissue or peripheral blood collected prior to treatment (pretreatment blood). For a population-based, case-control study, collection of pretreatment blood is a labor-intensive effort. An alternative is to collect blood from cases at interview, as is done for controls, after breast cancer treatment has commenced (posttreatment blood). It is unknown whether treatment affects blood levels of the organochlorines 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) or polychlorinated biphenyls (PCBs). The purpose of this study was to determine whether pretreatment versus posttreatment blood samples yielded significantly different estimates of cumulative exposure to DDE and PCBs among newly diagnosed breast cancer patients. Two-ml blood samples were collected prior to and after treatment for breast cancer from 22 nonfasting women, ages 45-87 years, newly diagnosed with invasive disease. Treatment was defined as major surgery (mastectomy or node removal), radiation, hormones (tamoxifen), or chemotherapy. Pretreatment and posttreatment blood samples were assayed for DDE and PCBs in blinded, matched pairs. The reported concentrations (volume basis) were adjusted for estimated total plasma lipids. For DDE, mean differences in unadjusted [0.99 ng/ml; 95% confidence interval (CI), -0.36 to 2.34 ng/ml] and lipid-adjusted (0.05 microgram/g lipid; 95% CI, -0.04 to 0.13 microgram/g lipid) levels were small. For PCBs, the unadjusted (0.68 ng/ml; 95% CI, 0.05 to 1.30 ng/ml) and adjusted (0.070 microgram/g lipid; 95% CI, -0.009 to 0.149 microgram/g lipid) mean differences were of borderline statistical significance. The mean percent change in lipid-adjusted organochlorine levels did not vary substantially between treatment groups, except for those patients receiving chemotherapy [n = 5; 15.8% (DDE), 29.4% (PCBs)]. Adjusted mean differences also increased with increasing time between the pretreatment and posttreatment blood draws. In multiple regression models that included treatment, age, race, stage, and time between blood draws, only chemotherapy appeared to predict the percent change in adjusted pretreatment and posttreatment levels of DDE or PCBs (P = 0.10 and 0.06, respectively). Posttreatment blood samples drawn within 3 months of pretreatment samples, with the exception of those drawn after the commencement of chemotherapy, provide similar measures of DDE body burden levels among breast cancer cases. The use of blood samples collected after treatment, rather than before treatment, for characterizing PCB levels may lead to misclassification of exposure.

Aged↗
PubMed1996

Phase I trial of sulindac plus 5-fluorouracil and levamisole: potential adjuvant therapy for colon carcinoma.

Epidemiological studies indicate that nonsteroidal anti-inflammatory agents may reduce colorectal cancer incidence and mortality. Moreover, sulindac has been shown to attenuate the growth and progression of colonic neoplasms in an experimental model of colon carcinoma and in patients with familial adenomatous polyposis. To determine whether sulindac (300 mg/day) would increase toxicity associated with 5-fluorouracil (5-FU) and levamisole, 15 patients with advanced colorectal cancer were treated. Median treatment duration was 3 (range, 0.6-6.0) months, and median age was 56 years (33% >/= 60 years). All patients had failed prior 5-FU-based therapy, had measurable disease, and were evaluable for toxicity. Grade III/IV granulocytopenia occurred in four patients; three patients had received prior pelvic irradiation resulting in a predisposition to myelosuppression. Two patients developed grade III anemia, and occult gastrointestinal bleeding was suspected in one. No other grade II or greater gastrointestinal or other nonhematological toxicity occurred. One patient had a partial response, 3 patients had disease stabilization, and 10 patients progressed on study. Our results indicate that sulindac does not significantly increase short-term toxicity associated with 5-FU and levamisole. To determine whether sulindac increases the efficacy of adjuvant chemotherapy, we propose a phase III randomized trial in patients with lymph node-positive colon cancer.

Adult↗
PubMed1995

Randomized phase III study of 5-fluorouracil plus high dose folinic acid versus 5-fluorouracil plus folinic acid plus methyl-lomustine for patients with advanced colorectal cancer.

BACKGROUND: Metastatic colorectal cancer is generally incurable. The most active regimen available, 5-fluorouracil (5-FU) and folinic acid (Leucovorin), produces response rates of approximately 25% to 30%. Methyl-lomustine is a nitrosourea with modest activity against colorectal cancer. A randomized trial was undertaken to evaluate the impact the addition of methyl-lomustine would have on response, duration of survival, and survival rates in patients with advanced colorectal cancer. METHODS: The methyl-lomustine/5-FU/Leucovorin (MFL) regimen consisted of methyl-lomustine (110 mg/m2), administered on Day 1 of each 8-week cycle with six weekly boluses of 5-FU (600 mg/m2), and Leucovorin (500 mg/m2). The FL treatment arm consisted of the administration of 5-FU and Leucovorin as described above. Patients were evaluated for response and toxicity after each 8-week cycle. RESULTS: Of 319 patients included in this trial, 297 (93.1%) had disease evaluable for response and toxicity: 145 received MFL, and 152 received FL. In this trial, 526 courses of MFL and 529 courses of FL were administered. Methyl-lomustine/5-FU/Leucovorin treatment resulted in 4 complete and 30 partial responses (response rate, 21.9%), and FL treatment resulted in 9 complete and 33 partial responses (response rate, 26.4%). There was no significant difference in median survival duration between patients in the two arms (MFL = 48 weeks, FL = 51 weeks). However, MFL was significantly more toxic with greater myelosuppression than was FL (Grade 3-4 neutropenia: MFL = 56 patients, FL = 27 patients, P < 0.001; Grade 3-4 thrombocytopenia: MFL = 49 patients, FL = 2 patients, P < 0.001; Grade 3-4 anemia: MFL = 15 patients, FL = 6 patients, P < 0.001; and more prolonged median duration of granulocytopenia: MFL = 9 days, FL = 7 days, P < 0.001; and thrombocytopenia: MFL = 14 days, FL = 7.5 days, P < 0.001). CONCLUSION: Because the addition of methyl-lomustine in the MFL schedule markedly increased the toxicity of the regimen and because the FL regimen was as effective as MFL, the authors recommend that Leucovorin and 5-FU remain the treatment choice for treating patients with metastatic colorectal cancer.

Adult↗
PubMed1995

Preoperative infusional chemoradiation therapy for stage T3 rectal cancer.

PURPOSE: To evaluate preoperative infusional chemoradiation for patients with operable rectal cancer. METHODS AND MATERIALS: Preoperative chemoradiation therapy using infusional 5-fluorouracil (5-FU), (300 mg/m2/day) together with daily irradiation (45 Gy/25 fractions/5 weeks) was administered to 77 patients with clinically Stage T3 rectal cancer. Endoscopic ultrasound confirmed the digital rectal exam in 63 patients. Surgery was performed approximately 6 weeks after the completion of chemoradiation therapy and included 25 abdominoperineal resections and 52 anal-sphincter-preserving procedures. RESULTS: Posttreatment tumor stages were T1-2, N0 in 35%, T3 N0 in 25%, and T1-3, N1 in 11%; 29% had no evidence of tumor. Local tumor control after chemoradiation was seen in 96% (74 out of 77); 2 patients had recurrent disease at the anastomosis site and were treated successfully with abdominoperineal resection. Overall, pelvic control was obtained in 99% (76 out of 77). The survival after chemoradiation was higher in patients without node involvement than in those having node involvement (p = n.s.). More patients with pathologic complete responses or only microscopic foci survived than did patients who had gross residual tumor (p = 0.07). The actuarial survival rate was 83% at 3 years; the median follow-up was 27 months, with a range of 3 to 68 months. Acute, perioperative, and late complications were not more numerous or more severe with chemoradiation therapy than with traditional radiation therapy (XRT) alone. CONCLUSIONS: Excellent treatment response allowed two-thirds of the patients to have an anal-sphincter-sparing procedure. Gross residual disease in the resected specimen indicates a poor prognosis, and therapies specifically targeting these patients may improve survival further.

Adenocarcinoma↗
PubMed1995

Cigarette smoking and spontaneous abortion of known karyotype. Precise data but uncertain inferences.

Data from the first phase (1974-1979) of this New York City case-control study showed that 1) cigarette smoking during pregnancy was associated positively with chromosomally normal spontaneous abortion and 2) both past and current smoking were associated inversely with trisomic loss in women under age 30 years and positively in older women. The authors used data from two subsequent study phases (1979-1982 and 1982-1986) to test the stability of these associations over time and the homogeneity between payment groups (private vs. public). Spontaneous abortions (cases) were classified as chromosomally normal (n = 1,388), trisomic (n = 557), or other chromosomally aberrant (n = 409). Controls (n = 4,165) were women who had registered for prenatal care before 22 weeks' gestation and delivered at 28 weeks or later. For chromosomally normal loss, later data gave modest support to prior observations. In the total sample, current smoking (defined as smoking during the month of the last menstrual period) of 14 or more cigarettes per day was increased among chromosomally normal cases in comparison with controls (adjusted odds ratio (OR) = 1.3, 95% confidence interval (CI) 1.1-1.7) and in comparison with other aberrant cases (adjusted OR = 1.2, 95% CI 0.8-1.8). Stronger associations in public patients than in private patients (adjusted odds ratios of 1.4-1.5 versus 0.8-0.9, respectively) might indicate either a mediating effect of social disadvantage or a chance fluctuation. For trisomic loss, later data did not support prior observations. Associations between trisomy and past or current smoking did not vary significantly with age in either payment group; assuming no effect modification of age, adjusted odds ratios for smoking in relation to trisomy were 0.9-1.0.

Abortion, Spontaneous↗