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Biomedical subjects

L Levin

Publications and source records attributed to L Levin.

At least 55 records · Page 3Linked to original sources
PubMed1998

Markers of cell proliferation in normal epithelia and dysplastic leukoplakias of the oral cavity.

The expression of several markers of epithelial cell proliferation was analyzed to establish baseline data for future chemoprevention studies of oral premalignant lesions. Punch biopsies (n = 60) from three different sites of oral mucosa (bucca, lateral tongue, and the floor of the mouth) were obtained from 20 normal donors of both sexes. After formaldehyde fixation and paraffin embedding, immunohistochemistry was used to detect the proliferation markers Mib-1, cyclin D1, and centromere-associated protein CENP-F. Analysis of sections stained for the three markers showed similar patterns, i.e., a low labeling index (LI) in the basal layer and a high LI in the parabasal layer at all three intraoral sites. No proliferative activity was seen above the parabasal layer (superficial layer). All sites showed similar Mib-1 LI values for the proliferative markers. The tongue epithelium exhibited higher parabasal LIs of cyclin D1 and CENP-F than did the other two sites. No significant differences were detected between smokers and nonsmokers. The data from normal mucosa were compared with those from low (n = 30)- and high (n = 17)-grade dysplastic leukoplakias. The Mib-1 LI showed a very significant change, with a 9-fold increase in the basal layer LI in dysplastic leukoplakias. Cyclin D1 and CENP-F showed similar trends with increments of up to 7-fold in the basal layer of high-grade dysplasia. Although the proliferative activity of the parabasal layer was similar in normal and leukoplakic epithelia, the superficial layer showed a significant increment in proliferative activity mainly in high-grade leukoplakia. These studies suggest that proliferation markers in the basal and superficial cells of premalignant lesions may serve as surrogate end point biomarkers for chemoprevention trials.

Antigens, Nuclear↗
PubMed1997

O6-Alkylguanine-DNA alkyltransferase in normal colon tissue and colon cancer.

O6-Alkylguanine-DNA alkyltransferase (AGT) is a DNA repair protein that reverses alkylation damage produced by chloroethylnitrosoureas and is a major determinant of cellular resistance to adjuvant chemotherapy with these drugs. AGT activity was measured in 119 samples from 69 patients, including normal, tumor, and diseased tissue, and 42 patients in which both normal and tumor tissue were assayed. The activity varied among individuals, but there was no statistically significant difference in average AGT activity among tumor, normal, and diseased tissue, or between men and women, or between young and old patients (< 70 or > 70 years). Few (3/49) tumor samples showed an absence of AGT activity (Mer- phenotype). The results indicate that nearly all colon cancers have significant AGT activity, and adjuvant chloroethylnitrosoureas chemotherapy must be modified, perhaps by the use of AGT biochemical modulators, to overcome this natural drug resistance.

Adolescent↗
PubMed1996

A profile of human immunodeficiency virus-infected adolescents receiving health care services at selected sites in the United States.

OBJECTIVE: To determine the demographic/clinical profile of human immunodeficiency virus (HIV)-infected adolescents in care at selected sites. METHODS: We mailed surveys requesting prevalence data from physicians in government-funded HIV research and care programs on HIV-infected youth (10-21 years) receiving care. RESULTS: A total of 49% responses yielded information on 978 subjects. Vertical, blood, and sexual were predominant transmission modes. Three-quarters were of an ethnic/racial minority; 50% were female. The earliest median CD4 count was 0.467 x 10(9)/liter (467/microliter). Percent asymptomatic varied by transmission: vertical (16%), blood products (40%), male-male sexual (67%) and female-male sexual (M:73%) (F:74%). Clinical indicated Pneumocystis carinii pneumonia prophylaxis was differentially prescribed: vertical (96%), blood (89%), and sexually (male-male-47%) (female-male: M: 36% and F: 56%). Of these youth 78% are not represented in national AIDS case data. CONCLUSIONS: Examination of numerator data from selected sites indicates three transmission-driven adolescent HIV epidemics with different characteristics. Minority youth are disproportionately represented; many vertically infected infants are surviving to adolescence; sexual activity is a significant transmission avenue. HIV-infected youth appear to enter care with considerable immunosuppression. Clinical profiles and treatment patterns appear to differ by transmission mode. Further study is needed on adolescent HIV disease progression and determinants of access to care and treatment.

Adolescent↗
PubMed1996

Refractory ceramic fiber exposure and pleural plaques.

Refractory ceramic fibers (RCF) are manmade vitreous fibers (MMVF) manufactured for high-temperature applications. Between 1987 and 1992, a retrospective cohort and nested case-control study evaluated chest radiographs from 652 workers involved in the manufacture of these fibers for plausibility of a causal relationship between exposure to RCF and chest-radiographic changes. The exposure-response relationship was modeled with three variables: years since first fiber production job, years in fiber production, and cumulative fiber exposure to date of study X-ray. The case-control study used a comprehensive characterization of possible asbestos exposure to investigate asbestos as the potential causative agent of chest-radiographic changes. Chest radiographs of 20 workers (3.1%) demonstrated 19 pleural plaques and one diffuse pleural thickening. Nine of 72 workers (12.5%) with more than 20 yr since their first fiber-production job had plaques (odds ratio [OR] = 9.5; 95% confidence interval [CI] = 1.9 to 48.2). Five of 19 workers with more than 20 yr in fiber-production work (26.3%) had plaques (OR = 22.3; 95% CI = 3.6 to 137.0). Similarly, adjusted ORs demonstrated a progressive relationship between cumulative fiber-months per milliliter (fiber-mo/ml) exposure and plaques. The case-control study confirmed that asbestos exposure did not account for the observed association between fiber exposure and plaques. A validity review of historical films demonstrated biologic plausibility for the association, since sufficient latency existed from the time of first RCF exposure to the development of plaques. There was no significant increase in parenchymal changes consistent with interstitial fibrosis.

Asbestosis↗
PubMed1995

The use of health risk assessment to estimate desirable sampling detection limits.

The inclusion of non-detected chemicals in a health risk assessment may lead, in some cases, to estimated risks that exceed regulatory thresholds, because one must use the detection limit or half of the detection limit. This study presents a methodology which will allow one to estimate appropriate detection limits by conducting a health risk assessment prior to the source sampling program. The advantages and shortcomings of various levels of detail in the risk assessment to determine those detection limits are discussed. The application of the methodology is demonstrated with a case study of the potential health effects of power plant stack emissions.

Environmental Monitoring↗
PubMed1995

Emotional response and corticoadrenal function in anterodorsal thalami nuclei lesioned rats.

In male and female rats, the effect of limbic anterodorsal thalami nuclei lesions (ADTN) on the emotional reactivity and their relationship with corticoadrenal function were studied. The emotional reactivity was evaluated by means of the open-field test and the corticoadrenal function by means of plasma anol adrenal corticosterone concentration. The results demonstrate that, on the 8th or 9th day after the lesion, the male rats show lack of habituation and the female ones, an increase in emotional reactivity. They also indicate that the lesion of ADTN does not affect the corticoadrenal response to exposure to novel situations.

Adrenal Cortex↗
PubMed1995

Crohn's disease and colorectal carcinoma: rectal cancer complicating longstanding active perianal disease.

OBJECTIVES: Reports of Crohn's disease (CD)-associated colorectal carcinoma are being cited in the medical literature with increasing frequency. Our aim was to identify subgroups of patients with risk factors that may account for this. METHODS: We reviewed the medical records of 16 patients with the simultaneous diagnosis of CD and colorectal carcinoma and, in addition, reviewed previously reported cases of CD-associated colorectal carcinoma. RESULTS: Eight male and eight female patients presented with 18 carcinomas: four right colon, four transverse, two descending colon, and eight rectal lesions. Median age at presentation was 48 yr. The mean duration of CD before presentation of carcinoma was 19.7 yr. Two lesions were discovered in strictured bowel segments. Two patients had multiple cancers. One had simultaneous cecal and left colon adenocarcinomas. The other underwent resection of a right colon lesion and 5 yr later presented with transverse colon carcinoma. Eight patients had rectal cancer; all were diagnosed preoperatively. Six of these patients had a history of severe perianal CD. Six had undergone multiple incision and drainage procedures for perirectal abscesses and fistulas. Two developed malignancies in defunctionalized rectal stumps. One of these patients presented with simultaneous squamous rectal carcinoma and papillary bile duct cholangiocarcinoma. CONCLUSIONS: Gastrointestinal malignancy in association with CD has been reported. Symptoms of chronic inflammatory disease may obscure clinical manifestations of occult malignancy and thereby delay diagnosis. Crohn's patients with long-standing anorectal or perianal disease and stricture may well warrant surveillance endoscopy and biopsy of involved areas with the hope of earlier detection and treatment of these rectal cancers.

Adult↗
PubMed1994

Effects of 3-month amino acid dialysis compared to dextrose dialysis in children on continuous ambulatory peritoneal dialysis.

OBJECTIVES: To compare the nutritional and biochemical effects of amino acid dialysis to dextrose dialysis in children receiving continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Prospective randomized crossover study. SETTING: Pediatric Nephrology Unit in a tertiary care, teaching hospital of the University of Toronto. PATIENTS: Seven children aged 0.7-16.5 years receiving CAPD. All patients had poor linear growth, with 5 patients showing evidence of energy deficit. INTERVENTIONS: Each patient received either amino acid or dextrose dialysate for 3 months, then crossed over to the alternate regimen for a subsequent 3 months. MAIN OUTCOME MEASURES: Nutritional and biochemical data were obtained on each patient during each dialysis regimen. RESULTS: Analysis of the patients' nutritional data showed comparable weight gain with both regimens but no significant improvement in lean body mass with either regimen. Appetite improved in most patients during amino acid dialysis. Biochemical data during amino acid dialysis showed a tendency to higher plasma potassium and urea levels with no clinical side effects or worsening of acidosis; however, there was a reduced anion gap and increased total plasma protein, due mostly to a rise in plasma albumin and a smaller increase in immunoglobulins. With the exception of tryptophan, fasting amino acid levels at the start and end of amino acid dialysis did not show any significant change. An interesting phenomenon of early blunting of the rise in amino acid levels, following a single amino acid dialysate exchange, was noticed at the end of the amino acid dialysis period. This newly described phenomenon could have been due to tolerance or hepatic enzyme induction. CONCLUSIONS: Overall amino acid dialysis was comparable to dextrose dialysis with no additional proven nutritional benefit, was equally effective in ultrafiltration and creatinine clearance, and produced no adverse clinical or biochemical effects.

Acid-Base Equilibrium↗
PubMed1993

Importance of multiagent chemotherapy regimens in ovarian carcinoma: dose intensity analysis.

BACKGROUND: In the previous meta-analysis of dose intensity (dosage) of chemotherapy in advanced ovarian cancer, we analyzed data on cyclophosphamide, altretamine (hexamethylmelamine), doxorubicin, and cisplatin. Only cisplatin showed statistically significant association of complete and partial clinical response with dose intensity. PURPOSE: This analysis updates the previous results and further characterizes response to cisplatin alone or in multiagent regimens. METHODS: We analyzed data from 18 regimens containing platinum (cisplatin or carboplatin) that were used in nine new randomized trials, in addition to data from the 60 groups of patients in our previous study in which responses were reported. Relative dose intensity was calculated as a fraction of the dosage of a drug in the standard regimen of cyclophosphamide, altretamine, doxorubicin, and platinum (CHAP). We performed single and multiple regression analyses to determine the relationship between disease outcome and relative dose intensity for cyclophosphamide, platinum, and doxorubicin alone or in combination. RESULTS: The association between outcome and dose intensity for platinum alone or in multiagent regimens was statistically significant. This association was of borderline significance for cyclophosphamide alone but was not significant for this drug in multiagent regimens. There were insufficient data to test the relationship for doxorubicin as a single agent, but in multiagent regimens, the relationship was borderline (P = .05). Multiagent regimens containing platinum produced greater response rates than platinum alone for any fixed, planned relative dose intensity for platinum. CONCLUSIONS: Our results support other published findings that use of cyclophosphamide and doxorubicin increases the efficacy of single-agent platinum. Relative dose intensity values for cyclophosphamide used alone were larger than those used in multiagent regimens, which might explain why the relationship between relative dose intensity and outcome for cyclophosphamide was not significant for use in multiagent regimens. Similarly, none of the multiagent regimens incorporated doxorubicin at a relative dose intensity for which the drug is found to be effective as a single agent. IMPLICATIONS: Prospective clinical trials are required to test the effect of higher relative dose intensity for doxorubicin and cyclophosphamide added to platinum in advanced ovarian cancer. An important element in the design of prospective trials will be to test for the relative importance of dose intensity versus total dose. This testing is best achieved in a three-arm study design such as that reported in adjuvant treatment of stage II breast cancer conducted by the Cancer and Leukemia Group B.

Altretamine↗
PubMed1993

Advanced ovarian cancer. An overview of multi-variate analyses of prognostic variables with special reference to the role of cytoreductive surgery.

BACKGROUND: Cytoreductive surgery is still widely believed to be a cornerstone in the management of advanced ovarian cancer. In the absence of data from prospective randomized trials, multi-variate analysis can assist in evaluating the role of optimal surgical cytoreduction relative to other possible prognostic variables. MATERIALS AND METHODS: Published analyses of prognostic variables have been reviewed and the consistency and reproducibility of variables have been considered. RESULTS: When reviewing the most recent literature it is obvious that there is a need to develop a consensus as to the most important patient characteristics which should be reported. Furthermore, these characteristics need to be standardized as do definitions such as toxicity, grading, and response criteria and duration. Subjective variables such as performance status, histological grading and typing, present a special problem as these lack reproducibility. The overview of multi-variate analyses for prognostic variables such as residual tumour size, tumour size prior to cytoreductive surgery, cisplatin therapy, grade, stage, histology, and performance status demonstrates that the impact of individual prognosticators depends on the indicators included in the analysis and that the importance of these variables could change as new technologies and treatments are introduced. CONCLUSIONS: The collection of a single data base including all known variables reported for each patient with appropriate attention to the careful evaluation of subjective indicators should be undertaken, with a view to establishing a prognostic index. This would allow the relative risk for individual patients to be assessed.

Clinical Trials as Topic↗
PubMed1993

Kidney cancer and hydrocarbon exposures among petroleum refinery workers.

To evaluate the hypothesis of increased kidney cancer risk after exposure to hydrocarbons, especially those present in gasoline, we conducted a case-control study in a cohort of approximately 100,000 male refinery workers from five petroleum companies. A review of 18,323 death certificates identified 102 kidney cancer cases, to each of whom four controls were matched by refinery location and decade of birth. Work histories, containing an average of 15.7 job assignments per subject, were found for 98% of the cases and 94% of the controls. To each job, industrial hygienists assigned semiquantitative ratings for the intensity and frequency of exposures to three hydrocarbon categories: nonaromatic liquid gasoline distillates, aromatic hydrocarbons, and the more volatile hydrocarbons. Ratings of "present" or "absent" were assigned for seven additional exposures: higher boiling hydrocarbons, polynuclear aromatic hydrocarbons, asbestos, chlorinated solvents, ionizing radiation, and lead. Each exposure had either no association or a weak association with kidney cancer. For the hydrocarbon category of principal a priori interest, the nonaromatic liquid gasoline distillates, the estimated relative risk (RR) for any exposure above refinery background was 1.0 (95% confidence interval [CI] 0.5-1.9). Analyses of cumulative exposures and of exposures in varying time periods before kidney cancer occurrence also produced null or near-null results. In an analysis of the longest job held by each subject (average duration 9.2 years or 40% of the refinery work history), three groups appeared to be at increased risk: laborers (RR = 1.9, 95% CI 1.0-3.9); workers in receipt, storage, and movements (RR = 2.5, 95% CI 0.9-6.6); and unit cleaners (RR = 2.3, 95% CI 0.5-9.9).

Carcinoma, Renal Cell↗
PubMed1993

Advanced ovarian cancer. Dose intensity.

BACKGROUND: The rationale for dose intensity is based on pre-clinical observations in experimental model systems of cancer as well as upon retrospective studies correlating the impact of dose intensity upon response rates and survival. MATERIALS AND METHODS: A review has been performed based on trials attempting to compare the effects of two different dose intensities of either cisplatin or carboplatin, combinations of cisplatin and carboplatin, combined platinum with additional agents, and high-dose chemotherapy, regimens requiring hematologic support. RESULTS: The early phase II trials suggested that there may be an important dose response range over clinically achievable platinum doses, but randomized trials have failed to consistently show a clinically significant improvement with high-dose therapy. Reasons for this may be differences in patient selection, that total dose is the most important factor, or that a more than two-fold increase in dose intensity is needed to detect differences in response and survival rates. Phase I and II studies indicate that high, but short lasting, response rates can be achieved with high-dose therapy with haematopoietic support in refractory patients, but the toxicity is substantial. Paclitaxel dose intensity is presently being studied in several trials. CONCLUSIONS: Future trials of dose intensity should be focused upon patients with small volume disease and drug sensitive tumours.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Two phase I studies of carboplatin dose escalation in chemotherapy-naive ovarian cancer patients supported with granulocyte-macrophage colony-stimulating factor.

Recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) may reduce myelosuppression and, thus, allow dose escalation of certain chemotherapeutic agents. We conducted two sequential phase I trials of escalating doses of carboplatin and a fixed dose and schedule of rHuGM-CSF in ovarian cancer patients who had not previously had chemotherapy, i.e., chemotherapy-naive patients. In the first trial, patients were assigned to regimens of increasing dose levels of carboplatin (starting at 400 mg/m2) and fixed doses and schedules of cyclophosphamide (600 mg/m2) and rHuGM-CSF (10 micrograms/kg given subcutaneously once daily on days 2-11). Chemotherapy was given every 3 weeks (regimen A). In the subsequent trial, the design was the same except that cyclophosphamide was omitted (regimen B). Fifteen patients received regimen A, and seven patients received regimen B. In regimen A, all three patients treated at the first dose level tolerated five cycles at full doses. Hematologic toxicity was dose limiting at the 600-mg/m2 dose level. When 500 mg/m2 carboplatin was given, six of eight patients tolerated three or four cycles at full doses before requiring dose reductions or treatment delays. In regimen B, doses could not be escalated above the first dose level (600 mg/m2) because of severe hematological toxicity. Nonhematological toxicity was tolerable and managed with acetaminophen, antihistamines, and/or nonsteroidal, anti-inflammatory medication. Compliance was excellent. We conclude that (a) rHuGM-CSF can be given safely and reliably to chemotherapy-naive ovarian cancer patients receiving these treatment regimens, (b) early and severe thrombocytopenia was a major problem with or without cyclophosphamide with doses of carboplatin at or above 600 mg/m2, and (c) 500 mg/m2 carboplatin administered every 3 weeks is the highest dose in regimen A that can be given safely in the outpatient setting.

Antineoplastic Combined Chemotherapy Protocols↗