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Biomedical subjects

B Levin

Publications and source records attributed to B Levin.

At least 127 records · Page 7Linked to original sources
PubMed1995

Cigarette smoking and alcohol consumption as risk factors for colorectal adenomatous polyps.

BACKGROUND: Results of epidemiologic studies suggest that there is limited evidence for the association between cigarette smoking and risk of colorectal cancer. Cigarette smoking has been shown to increase the risk of colorectal adenomatous polyps, which are recognized as precursors of colorectal cancer, while few studies have examined the association between alcohol consumption and the development of adenomatous polyps. PURPOSE: We examined the association between cigarette smoking, alcohol consumption, and the presence of colorectal adenomatous polyps. METHODS: Analyses were based on data from a case-control study of dietary and other lifestyle factors for colorectal adenomatous polyps. We assessed the risk of adenomatous polyps associated with total number of years of smoking, number of cigarettes smoked per day, and pack-years of smoking for past and current smokers separately. We also assessed the joint association between cigarette smoking and alcohol consumption on the risk of adenomatous polyps. RESULTS: Current smokers who smoked more than 20 pack-years were at significantly higher risk of adenomatous polyps compared with never smokers (odds ratio [OR] = 2.56; 95% confidence interval [CI] = 1.28-5.14). Past smokers also had an increased risk of having adenomatous polyps, but no clear trend was observed for pack-years of smoking. Alcohol consumption was positively associated with risk of adenomatous polyps. Compared with nondrinkers, the strongest risk was observed for individuals who consumed 2.31-9.46 g alcohol per day (OR = 2.23; 95% CI = 1.29-3.83), and a decrease in risk was observed for individuals who consumed 9.47-67.36 g alcohol per day (OR = 1.63; 95% CI = 0.92-2.88). Among current smokers, a joint effect was observed for individuals who smoked and drank compared with those who never smoked and were not current drinkers (OR = 4.21; 95% CI = 1.88-9.41). For past smokers, a significant joint effect of smoking and current alcohol consumption was also observed, but the risk was not as strong as that for current smokers (OR = 2.61; 95% CI = 1.40-4.87). CONCLUSIONS: These data provide further evidence of the positive association between cigarette smoking and the development of colorectal adenomatous polyps. The combination of cigarette smoking and alcohol consumption increased the risk of adenomatous polyps. IMPLICATIONS: Future research should focus on the understanding of the role of cigarette smoking and alcohol consumption as these two factors relate to the evolution of colorectal adenomatous polyps and subsequent carcinogenesis.

Adenomatous Polyposis Coli↗
PubMed1995

bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis.

Apoptosis or programmed cell death represents a mechanism by which cells possessing DNA damage can be deleted. The bcl-2 proto-oncogene is a known inhibitor of apoptosis that may allow the accumulation and propagation of cells containing genetic alterations. To determine if and when the bcl-2 gene is activated during colorectal tumorigenesis and its relationship to p53, we analyzed normal mucosa, hyperplastic and dysplastic epithelial polyps, and carcinomas for the expression of these markers using immunohistochemistry. Whereas bcl-2 staining was restricted to basal epithelial cells in normal and hyperplastic mucosa, bcl-2 expression was detected in parabasal and superficial regions in dysplastic polyps and carcinomas. An inverse correlation was found between bcl-2 and p53 expression in adenomas, suggesting that these markers may regulate a common cell death pathway. Furthermore, carcinomas with a high percentage of bcl-2-positive cells were significantly more likely to have low rates of spontaneous apoptosis, as determined histologically, than those cancers with low or absent bcl-2 expression. Abnormal activation of the bcl-2 gene appears to be an early event in colorectal tumorigenesis that can inhibit apoptosis in vivo and may facilitate tumor progression.

Adenocarcinoma↗
PubMed1995

Consensus statement: octreotide dose titration in secretory diarrhea. Diarrhea Management Consensus Development Panel.

Octreotide is an effective therapeutic option in controlling secretory diarrhea of varied etiology. However, marked patient-to-patient differences in the antidiarrheal effects necessitate titration of octreotide dose in individual patients to achieve optimal symptom control. A consensus development panel established guidelines for octreotide dose titration in patients with secretory diarrhea. Overall, the panel recommended an aggressive approach in selecting the initial octreotide dose and in making subsequent dose escalations in patients with secretory diarrhea due to gastrointestinal tumors (eg, carcinoids, VIPomas), AIDS, dumping syndrome, short bowel syndrome, radiotherapy, or chemotherapy. To avoid hypoglycemia in patients with diabetes mellitus-associated secretory diarrhea, the panel recommended a low initial octreotide dose and a conservative titration regimen with close monitoring a blood glucose levels. The end point of therapy should focus on a reduction in diarrhea (frequency of bowel movements or stool volume) rather than normalization of hormonal profile. Overall, octreotide is well tolerated; principal side effects are transient injection site pain and gastrointestinal discomfort. For many patients with secretory diarrhea, octreotide therapy is expected to improve the overall health and quality of life and in the long run will lessen health care costs.

Carcinoid Tumor↗
PubMed1995

Hypericin as an inactivator of infectious viruses in blood components.

BACKGROUND: Hypericin is a potent virucidal agent with activity against a broad range of enveloped viruses and retroviruses. The effective virucidal activity emanates from a combination of photodynamic and lipophilic properties. Hypericin binds cell membranes (and, by inference, virus membranes) and crosslinks virus capsid proteins. This action results in a loss of infectivity and an inability to retrieve the reverse transcriptase enzymatic activity from the virion. STUDY DESIGN AND METHODS: Since hypericin is devoid of adverse action in most blood components and blood analyses, it is investigated as an additive with potential to inactivate infective viruses in blood components intended for transfusion. RESULTS: Complete inactivation of 10(6) tissue culture-infective doses of human immunodeficiency virus was obtained in whole blood and in diluted packed red cells after illumination with fluorescent light for 1 hour. Loss of viral infectivity to cultured CEM cells has been monitored by use of a detection assay for human immunodeficiency virus p55 in enzyme-linked immunosorbent assay and cytopathic assays. In physiologic media, hypericin interacts with albumin and lipoproteins, retaining the virucidal activity in bound form. The molecule is negatively charged and forms organic and inorganic monobasic salts (ion pairs) in physiologic pH. Various ion pairs differ in virucidal efficacy. CONCLUSION: The apparent transfusibility of hypericin, taken together with the efficacy of the virucidal activity, the broad range of enveloped viruses affected, and the absence of adverse effects on stored red cells, may render hypericin useful for inactivation of infectious viruses in red cells.

Anthracenes↗
PubMed1995

Phase II trial of isotretinoin and recombinant interferon alfa-2a in metastatic colorectal carcinoma.

Phase II trials of the novel biologic combination isotretinoin (13-cis-retinoic aid) plus recombinant interferon alfa-2a have demonstrated this combination's major activity against advanced squamous cell carcinoma of the skin and cervix. Because this combination has had limited study in other tumors, we initiated a phase II trial of this regimen in patients with metastatic colorectal adenocarcinoma. Sixteen patients with measurable metastatic colon carcinoma who had received no previous chemotherapy were entered on the trial. Patients received recombinant interferon alfa-2a, 6 million units a day subcutaneously, and isotretinoin, 1 mg/kg per day orally in two divided doses. Patients were evaluated for response after 8 weeks of treatment and then continued on therapy until progressive disease was documented. We did not observe complete or partial responses. Two patients experienced minor responses in measurable pulmonary metastases lasting 12 and 8 weeks. Grade 3-4 toxic reactions included fatigue (5 patients), granulocytopenia (6 patients), neurotoxicity (2 patients), and elevated serum triglyceride levels (2 patients). Although this combination has demonstrated significant activity in squamous cell carcinomas of the skin and cervix, our results suggest that it has little therapeutic activity against advanced colorectal adenocarcinomas.

Adenocarcinoma↗
PubMed1995

The role of dietary factors and chemoprevention in gastrointestinal malignancy.

Environmental factors, particularly pertaining to the diet, are of importance in the pathogenesis of gastrointestinal neoplasia. Increasingly sophisticated studies have begun to elucidate some of the mechanisms responsible for both the deleterious and protective effects of compounds ingested or smoked (such as tobacco). The new and developing field of chemoprevention holds great promise for the possibility of averting neoplasia by interfering with the metabolism of carcinogens, reducing their binding to the target cell, or even by suppressing the initiated cell.

Antioxidants↗
PubMed1995

Cancers of the stomach and the duodenum.

Gastric cancer remains the seventh most common cause of cancer death in the United States, and it is the most prevalent in populous areas, such as south China, Japan, and Korea. Duodenal cancers are rare; adenocarcinomas are the most common variety. We examine recent findings concerning pathogenesis, diagnosis, and management of gastric and duodenal malignancies.

Adenocarcinoma↗
PubMed1994

Nonsteroidal antiinflammatory drugs and human cancer. Report of an interdisciplinary research workshop.

BACKGROUND: Since the 1970s, work in several disciplines (toxicology, pharmacology, clinical medicine, epidemiology) increasingly has suggested that aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) may reduce the occurrence or progression of colorectal cancers and polyps and perhaps of other gastrointestinal tumors. The potential application of these findings for chemoprevention of such cancers in man now deserves serious consideration. METHODS: An interdisciplinary workshop was held by the American Cancer Society in March 1994 to review the current knowledge of NSAIDs and cancer and to seek a consensus on future research directions, particularly concerning the possibility of randomized prevention trials in human populations. RESULTS: A wide-ranging review was conducted of past and current research regarding (1) NSAIDs' effects in experimental animal cancer models; (2) clinic experience in NSAID treatment, particularly in familial polyposis; (3) pharmacologic studies regarding the enzymatic and metabolic actions of NSAIDs; and (4) epidemiologic observations on the relationship of aspirin/NSAID usage to colorectal cancer occurrence in human populations. CONCLUSIONS: Combined evidence from different research disciplines strongly supports the notion that aspirin and other NSAIDs act to prevent the development or progression of certain human gastrointestinal cancers, especially colorectal cancer. Consequently, the workshop recommended that randomized prevention trials be undertaken. For various logistic reasons, such trials probably should focus on NSAID effects on the occurrence and progression of colorectal polyps rather than on carcinoma itself. Continued research also is needed to clarify further the pharmacologic, clinical, and epidemiologic nature of NSAIDs' influences on human carcinogenesis.

Animals↗
PubMed1994

Evidence that protein kinase C-alpha activation is a critical event in phorbol ester-induced multiple drug resistance in human colon cancer cells.

We previously designed and characterized an in vitro model of the intrinsic drug resistance of human colon cancer. The human colonic epithelium is chronically exposed to endogenous protein kinase C (PKC) stimulatory factors, and our model demonstrated that activation of PKC induces resistance to multiple anticancer drugs in the metastatic human colon cancer cell line KM12L4a. PKC is an isozyme family with ten members, eight of which are phorbol ester-responsive. In this report, we show that thymeleatoxin (Tx), a daphnane tumor promoter that selectively activates the phorbol ester-responsive isozymes cPKC-alpha, -beta 1, -beta 2, and -gamma, was just as effective in inducing drug resistance in KM12L4a cells as phorbol dibutyrate, a potent activator of all phorbol ester-responsive PKC isozymes. The induction of resistance by Tx was associated with a reduction in cytotoxic drug accumulation in KM12L4a cells. We demonstrated by immunoblot analysis and hydroxylapatite chromatography that KM12L4a cells express active cPKC-alpha but not cPKC-beta 1, -beta 2, or gamma. Our results provide strong evidence that phorbol-ester activation of cPKC-alpha is sufficient for the induction of resistance observed in KM12L4a cells. The possibility that endogenous PKC activators may induce intrinsic drug resistance in clinical colon cancer by an analogous mechanism is strongly suggested by our detection of active cPKC-alpha in surgical specimens of human colon carcinomas.

Colonic Neoplasms↗
PubMed1994

Gastric mucosal injury after hepatic arterial infusion chemotherapy with floxuridine. A clinical and pathologic study.

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) of liver metastases of colon cancer with an implantable pump is associated with liver and gastrointestinal complications. METHODS: The authors retrospectively studied the clinical features and gastric histopathology of nine patients who received HAIC and had gastritis develop and in whom biopsy specimens were available. RESULTS: Gastritis was heralded in these patients by epigastric pain and tenderness, nausea, vomiting, weakness, and anorexia. In seven patients, 18 gastric ulcers were endoscopically detected. Mucosal damage developed despite prophylactic antiulcer therapy and healed only upon cessation of HAIC. These observations suggest that the predominant drug given, floxuridine, was the responsible toxic agent. Seventeen biopsy specimens were reviewed, and all exhibited varied histologic evidence of inflammation, reactive glandular changes, and cell necrosis. These mucosal changes were present even in tissues obtained from patients without ulcers. In addition, floxuridine-induced glandular atypia was noted in eight biopsy samples from six patients. The crowded glands were distorted and lined by large cells that included bizarre forms with pleomorphic nuclei. CONCLUSIONS: Gastric injury in HAIC appeared analogous to the general features encountered in reactive gastritis resulting from chemical irritants. The glandular atypia is peculiar to HAIC, and although the changes were morphologically alarming, in this clinical situation care should be exercised not to interpret floxuridine-induced atypia as carcinoma.

Adult↗
PubMed1994

Characteristics of a hypothetical group of hospital controls for a case-control study.

In case-control studies in which cases are ascertained from hospitals, controls are frequently chosen from among patients with other diseases at the same hospitals. This study was undertaken to examine the extent to which a hospital control group is representative of the population to which inferences are made. A hypothetical hospital control group was assembled consisting of 233 men and women aged 40-74 years who were surgical inpatients at the two hospitals in Otsego County, New York, in 1990. The characteristics of this group were compared with the characteristics of 15,563 men and women aged 40-74 years who participated in a privately conducted health census in the same county in 1989 with the use of health-related data collected in the census. In this rural setting, only small differences were found between the hospital control group and the census population on most of the measures considered, including demographic characteristics, certain health behaviors, and the prevalence of common conditions. However, the female hospital controls were more likely to be overweight than the females enumerated in the census, and the men were more likely to have ever smoked cigarettes. These differences were large enough to lead to different interpretations about the strength of the associations between these variables and case-control status.

Adult↗
PubMed1994

Posterior temporal epilepsy: electroclinical features.

In the course of evaluating children with posterior temporal lobe epilepsy with subdural electrodes, we observed that their seizures commonly arose from basal rather than convexity foci and that they followed a stereotyped clinical sequence. Seizures characteristically began with behavioral arrest that coincided with basal temporal seizure discharges and progressed to motor signs as the seizure activity spread to the ipsilateral cortical convexity. Behavioral automatisms were observed in approximately half the patients, but were never the first or most prominent ictal manifestation. Focal lesions were identified preoperatively in 7 patients. We performed tailored temporal lobe resections in 14 patients, 10 (71%) of whom were seizure free (N = 9) or had occasional auras (N = 1) at a mean follow-up of 2 years. These findings suggest that in childhood, posterior temporal seizures frequently arise from basal cortex and have a consistent and recognizable ictal and electrographic semiology. In medically refractory patients, tailored temporal resection is an effective therapy.

Adolescent↗
PubMed1994

Clinical pharmacology and tissue disposition studies of 131I-labeled anticolorectal carcinoma human monoclonal antibody LiCO 16.88.

Antibody LiCO 16.88 is a human IgM recognizing a 30- to 45-kDa intracytoplasmic antigen present in human adenocarcinoma cells. An 8-mg sample of antibody labeled with 5 mCi 131I was co-administered i.v. with 120 mg (three patients), 240 mg (three patients) or 480 mg (four patients) unlabeled antibody as a 4-h infusion. The plasma half-life was 24 +/- 1.2 h and the immediate apparent volume of distribution was 5.2 +/- 0.2 l at the 28-mg dose level. The plasma half-lives and the cumulative urinary excretion of radiolabel did not seem to vary significantly with increasing doses of unlabeled antibody. However, both the volume of distribution and the clearance rate from plasma increased significantly with increasing antibody dose. Uptake of antibody into tumor tissues obtained during laparotomy 8-9 days after administration varied between 0.00002% ID/g and 0.00127% ID/g. In five of seven patients, the tumor content of antibody was higher than that in adjacent normal tissue. Tumor-to-normal tissue ratios ranged from 0.8 to 10 (mean = 3.8 +/- 1.0). In general, the higher radioactivity(cpm)/g tumor was confirmed by both immunoperoxidase and autoradiography. Antibody 16.88 localizes in tumors after administration and may be considered for use in radioimmunotherapy trials.

Antibodies, Monoclonal↗
PubMed1994

Phase II trial of docetaxel (Taxotere) in metastatic colorectal carcinoma.

BACKGROUND: Docetaxel (Taxotere) is prepared from a noncytotoxic precursor extracted from the needles of the Taxus baccata. Preclinical investigations have demonstrated that docetaxel is very active in colon adenocarcinoma murine models. Phase I studies revealed granulocytopenia to be the dose-limiting toxicity. Initial clinical trials also demonstrated docetaxel's activity in ovarian, breast, and non-small cell lung cancer. Because of this encouraging preclinical and clinical activity, we initiated a phase II study of docetaxel in patients with metastatic colorectal carcinoma. PATIENTS AND METHODS: Docetaxel, 100 mg/m2, was administered as a 1-hour intravenous infusion every 21 days. Nineteen patients were entered on the trial. All patients had measurable disease and had not received prior chemotherapy for metastatic disease. RESULTS: No complete or partial responses were observed. Granulocytopenia was the dose-limiting toxic effect. Seventeen patients had grade 4 granulocytopenia; 8 of these patients received antibiotics for neutropenic fevers. Twelve patients experienced hypersensitivity reactions, and 15 patients experienced cutaneous toxic reactions. One patient demonstrated evidence of fluid retention. CONCLUSIONS: Administered at the stated dose and schedule, docetaxel has little activity against metastatic colorectal carcinomas. The toxicity profile, consisting of granulocytopenia, hypersensitivity reactions, cutaneous reactions, and edema, has been previously described in patients receiving docetaxel.

Adenocarcinoma↗
PubMed1994

Phase II trial of edatrexate in patients with advanced hepatocellular carcinoma.

BACKGROUND: The methotrexate analogue edatrexate (10-ethyl-10-deaza-aminopterin, or 10-EDAM) has demonstrated greater activity than methotrexate has against murine tumors and human tumor xenografts. Phase II trials of edatrexate have already demonstrated its activity against breast, lung, and head and neck carcinomas. A phase II trial of edatrexate was conducted in patients with advanced hepatocellular carcinoma. PATIENTS AND METHODS: Seventeen patients with previously untreated unresectable hepatocellular carcinoma were enrolled on the study. Edatrexate, 80 mg/m2 weekly for 5 weeks, was administered intravenously. The treatment course was repeated every 6 weeks. Tumor response was evaluated by computerized tomographic scan after 2 courses. RESULTS: No complete or partial responses were observed in this trial. Two minor responses, each lasting less than 12 weeks, were observed. Twelve patients had elevated serum alpha-fetoprotein (AFP) levels at entry into the study; 4 of the 12 patients experienced a > or = 25% decrease in the level of this tumor marker; 3 of the 4 had a > 50% reduction in AFP level. Grade 3 and 4 toxic effects were granulocytopenia, thrombocytopenia, anemia, oral mucositis, skin reactions, fatigue, anorexia, and diarrhea. CONCLUSIONS: Edatrexate administered at this dose and schedule appears to have little therapeutic efficacy against advanced hepatocellular carcinoma.

Adult↗