Search PubMed⌕ Search

Biomedical subjects

B Levin

Publications and source records attributed to B Levin.

At least 217 records · Page 12Linked to original sources
PubMed1989

Mechanisms of combined effects of gamma-interferon and 5-fluorouracil on human colon cancers implanted into nude mice.

The purpose of these studies was to determine the possible mechanisms responsible for the therapeutic effects of systemic administration of 5-fluorouracil (FUra) and gamma-interferon on disseminated human colon cancer. We used several human carcinoma cell lines that were established from different surgical specimens. Some lines were selected in nude mice for increased metastatic potential, and one line was selected in vitro for resistance to human recombinant gamma-interferon (r-IFN-gamma). In initial in vitro studies, FUra was cytostatic against all the human cell lines but did not produce cytolysis in any of the lines tested. The two r-IFN-gamma were species specific for both antitumor and immunomodulatory effects. Human r-IFN-gamma produced cytostatic and cytolytic effects against sensitive human colon carcinoma cells but did not activate tumoricidal properties in mouse macrophages. In contrast, mouse r-IFN-gamma had no direct cytotoxic effects against any of the human colon carcinoma lines but did activate tumoricidal properties in mouse macrophages. Human colon carcinoma cells (sensitive or resistant to human r-IFN-gamma) were implanted into the spleens of nude mice. Three days later, we began treatments with FUra and human or mouse r-IFN-gamma. In all experiments, the combination of FUra with mouse r-IFN-gamma produced the best therapeutic effects against growth of the cells in the spleen and in the liver. Because the mouse r-IFN-gamma is devoid of direct antitumor effects (against human tumor cells) but is a potent macrophage activator, these results suggest that the antitumor effects were due to direct antitumor effects of FUra and to activation of host defense mechanisms by the r-IFN-gamma.

Animals↗
PubMed1989

Predominant left hemisphere metabolic dysfunction in dementia.

Thirty-one patients with probable Alzheimer's disease and 11 patients with memory disorders, attributable to multiple cerebral infarctions, were studied using 18-F-fluorodeoxyglucose-positron emission tomography scans. Asymmetry in cerebral glucose metabolism within these diagnostic groups was assessed by comparison with the metabolic rates obtained in age-equivalent healthy control subjects. A significantly greater number of individuals in both patient groups exhibited predominant left rather than right hemisphere hypometabolism. In addition, for patients with Alzheimer's disease, the degree of asymmetry was not related to either the severity or duration of dementia. These findings could be explained by greater susceptibility of the left hemisphere to degenerative or ischemic brain disease, by a specific sampling effect, or most likely, by greater metabolic deficits resulting from left rather than right hemisphere impairment.

Brain↗
PubMed1989

Phase II study of adriamycin with sequential methotrexate and 5-fluorouracil (AMF) in gastric carcinoma.

The purpose of this study was to evaluate the response rate, methotrexate plasma levels, and toxicity of a three-drug regimen in patients with gastric carcinoma. A total of 37 patients with advanced measurable adenocarcinoma of the stomach were treated with Adriamycin, methotrexate, and 5-fluorouracil (AMF). Adriamycin and methotrexate were given as i.v. infusions on day 1; 24 h following methotrexate administration, patients received an i.v. infusion of 5-fluorouracil concomitantly with oral leukovorin factor (given over 48 h). Methotrexate levels were monitored regularly in all patients, and courses were repeated every 3 weeks. The median dose levels per course were 50 mg/m2 (range, 40-60 mg/m2) for Adriamycin, 1,000 mg/m2 (range, 650-1,250 mg/m2) for 5-fluorouracil, and 500 mg/m2 (range, 160-625 mg/m2) for methotrexate. Of 36 evaluable patients, 8 (22%) achieved an objective response, including 1 complete remission. Stable disease was noted in 11 patients and a minor tumor regression occurred in 1. The median survival duration of all patients was 6 months (range, 2-31+ months). AMF was well tolerated; toxicities were mild to moderate, most frequently involving nausea and vomiting, mucositis, and neutropenia with or without fever. There was no death directly attributable to chemotherapy. Although the AMF regimen used a well-documented preclinical concept of synergism between methotrexate and 5-fluorouracil, response and survival results suggest a modest activity of this combination in patients with gastric cancer. Better preclinical models are necessary for the development of effective combination chemotherapy.

Adenocarcinoma↗
PubMed1989

The use of microwave energy for processing acrylic resins.

Test strips of five different resins were processed with (1) microwaves by using a kitchen-type microwave oven, and (2) a conventional water bath. The strips were tested for hardness, porosity, and transverse strength. The results showed no significant difference between resin strips cured by either method. Maxillary dentures were waxed on stone casts of an aluminum model in another study. The dentures were processed with the same five resins, half by using microwave energy and the remainder with the water bath. The adaptation of the processed dentures to the aluminum cast was measured with feeler gauges. The results showed no statistically significant differences between dentures cured by either method. These studies demonstrated that the important physical characteristics of microwave-cured resin are approximately the same as resin cured in a conventional water bath. Curing dentures by microwave energy has the advantages of reduced curing time, ease, and cleanliness.

Acrylic Resins↗
PubMed1989

Effect of crossover on the statistical power of randomized studies.

Randomized studies involving long-term follow-up are vulnerable to the effects of unplanned crossover. In surgical studies, such crossover usually occurs when control patients become more symptomatic and undergo operation. In several large studies of coronary bypass grafting, crossover ranged from 25% to 38%. The most common way of dealing with this problem is to apply the "intention-to-treat" principle, which analyzes such crossovers with their originally assigned groups. Besides the logical problem of counting a control patient who actually undergoes operation as "nonsurgical," a more subtle problem arises in terms of statistical power. When statistical power is low, a truly effective treatment may be mistakenly labeled as no better than control, causing a potentially valuable form of therapy to be ignored or discarded. This analysis demonstrates that crossover may have a profound effect on the statistical power of randomized studies and presents a method for predicting the effect of such crossover on statistical power.

Coronary Artery Bypass↗
PubMed1989

Studies of the mechanisms of action of the antiretroviral agents hypericin and pseudohypericin.

Administration of the aromatic polycyclic dione compounds hypericin or pseudohypericin to experimental animals provides protection from disease induced by retroviruses that give rise to acute, as well as slowly progressive, diseases. For example, survival from Friend virus-induced leukemia is significantly prolonged by both compounds, with hypericin showing the greater potency. Viremia induced by LP-BM5 murine immunodeficiency virus is markedly suppressed after infrequent dosage of either substance. These compounds affect the retroviral infection and replication cycle at least at two different points: (i) Assembly or processing of intact virions from infected cells was shown to be affected by hypericin. Electron microscopy of hypericin-treated, virus-producing cells revealed the production of particles containing immature or abnormally assembled cores, suggesting the compounds may interfere with processing of gag-encoded precursor polyproteins. The released virions contain no detectable activity of reverse transcriptase. (ii) Hypericin and pseudohypericin also directly inactivate mature and properly assembled retroviruses as determined by assays for reverse transcriptase and infectivity. Accumulating data from our laboratories suggest that these compounds inhibit retroviruses by unconventional mechanisms and that the potential therapeutic value of hypericin and pseudohypericin should be explored in diseases such as AIDS.

Animals↗
PubMed1989

Disease by design.

Explore the source record for details and available documents.

Hospitalization↗
PubMed1989

Treatment of advanced colorectal cancer.

This article delineates the current status of clinical research into the chemotherapeutic treatment of advanced colorectal cancer. The data reviewed indicate that, despite an extensive series of trials, no new agents with significant activity have been identified. The most active single agent remains 5-fluorouracil (5-FU); efforts to enhance or modulate the activity of this drug with methotrexate, cisplatin, folinic acid, and N-(phosphonacetyl)-L-aspartic acid (PALA) are described. Of these approaches, combinations of 5-FU and folinic acid have been the most successful. Two recently reported studies suggest that patient survival is improved by this combination compared with 5-FU alone. Specialized applications of chemotherapy are also reviewed. Included is a description of the results of a recently conducted randomized trial of hepatic intra-arterial 5-fluorodeoxyuridine (FUDR) versus FUDR administered systemically. This study confirmed the improved response rate for patients receiving intra-arterially administered fluoropyrimidines but failed to substantiate a survival advantage over patients receiving intravenous therapy. Finally, newly evolving therapies such as hepatic-arterial chemoembolization, the use of new intra-arterial drugs, and high-dose systemic chemotherapy are reviewed. Directions for further clinical and basic scientific research are outlined.

Antineoplastic Agents↗
PubMed1989

Phase I and II studies of the combination of recombinant human interferon-gamma and 5-fluorouracil in patients with advanced colorectal carcinoma.

Based on the in vitro and in vivo data suggesting synergistic cytolysis by the combination of 5-fluorouracil and interferon-gamma against a variety of malignant cell lines including a human colon carcinoma cell line (HT-29), we initiated studies in patients with advanced colon or rectal carcinoma. Forty-six patients received 5-fluorouracil as an intravenous injection on days 1-5 and recombinant human interferon-gamma as an intramuscular injection on days 1-14, followed by a rest period of 14 days; courses were repeated every 28 days. In the phase I study, cohorts of two patients received a stepwise dose level increase to achieve the maximum tolerated dose (MTD), at which a total of six patients were studied. The dose levels constituting the MTD were as follows: 5-fluorouracil (500 g/m2/day) and recombinant gamma-interferon (0.5 mg/m2/day). Four patients achieved a partial response in the phase I study. In the phase II study, 30 patients received therapy at the MTD. Among 29 evaluable patients in the phase II study, two patients achieved a partial response. Common toxicities included malaise, fever, anorexia, nausea and vomiting, and diarrhea. Transient severe myelosuppression was common but did not result in significant morbidity. Our data suggest that the combination of 5-fluorouracil and recombinant gamma-interferon did not have the same antitumor effect in patients as it had in the preclinical experiments.

Adenocarcinoma↗
PubMed1989

Systemic and regional therapy of advanced islet cell tumors.

Asymptomatic patients with islet cell tumors should be observed every 3 to 6 months. Once symptomatic, many therapeutic choices exist. First choice would be symptomatic management resulting in minimum side effects. More aggressive approaches include systemic therapy with cytotoxic or biologic agents. Vascular occlusion provides useful palliation of liver metastases.

Adenoma, Islet Cell↗
PubMed1989

Chemoprevention of colon cancer.

Animal tumor experiments and epidemiologic studies suggest that several agents may be of potential value in blocking the development of colon adenomas and carcinoma. Recent laboratory investigations have demonstrated several intermediate markers that are altered in the colonic epithelium of high-risk individuals and that can be modulated by several possible chemopreventive agents. Calcium and ascorbic acid are two agents that have been investigated in preliminary studies. Although the results have not been striking, these studies have pointed up methodologic issues that must be addressed and will contribute greatly to the design of the next generation of trials. Given the advances in the elucidation of the carcinogenic processes in colon cancer, it is reasonable to hope that the next decade of research will discover chemoprevention strategies that will protect individuals from the development of the most common tumor in Western society.

Adenoma↗
PubMed1988

Phase II study of fludarabine phosphate in patients with advanced colorectal carcinoma.

For phase II studies in patients with solid tumors, the National Cancer Institute recommended that the starting dose of fludarabine phosphate be 20 mg/m2/day as a short intravenous infusion for 5 days every 21 days. Twenty-one patients with untreated, advanced, measurable colorectal carcinoma received fludarabine phosphate as a 30-minute infusion at a median dose of 25 mg/m2/day (range 15-35 mg/m2/day) for 5 consecutive days repeated every three weeks. Antitumor response was evaluated following two courses of therapy. No patient achieved complete or partial response. Minor regression of lung metastases occurred for less than 12 weeks in one patient. Therapy was generally well tolerated. Frequent toxicities included lymphopenia, mild nausea and vomiting, mucositis, and anorexia. One patient died of sepsis, bleeding, and progressive disease while she was severely myelosuppressed. Neurotoxicity was not observed in any patient. Fludarabine phosphate at this schedule and dose range is inactive against colorectal carcinoma.

Adult↗
PubMed1988

Acute leukemia occurring after radiotherapy and chemotherapy with a nitrosourea, PCNU.

Secondary acute leukemias can occur in patients who have been treated with chemotherapy. Several reports have shown that treatment with nitrosoureas can result in secondary leukemia, but this is the first report implicating the investigational drug PCNU as a cause. This case is unique because of the cytogenetic findings, the short latency period between the chemotherapy and the diagnosis of leukemia, and the successful treatment of the leukemia with high-dose cytarabine (ara-C).

Adenocarcinoma↗
PubMed1988

Sample size determination in studies with matched pairs.

Two modifications are made in Schlesselman's procedure for determining the total number of pairs to be studied in a case-control study with matching. One is to take account of the use of the continuity correction in the McNemar test statistic, and the other is to incorporate a measure of the degree of association induced by the matching variables between a case's exposure status and that of his or her matched control. The result of both modifications is to increase the required number of pairs above the number produced by Schlesselman's procedure.

Epidemiologic Methods↗
PubMed1988

Clinical and immunological studies of cadaveric renal transplant recipients given total-lymphoid irradiation and maintained on low-dose prednisone.

Twenty-five recipients of cadaveric renal transplants were given total lymphoid irradiation (TLI), perioperative antithymocyte globulin, and low-dose prednisone as the sole maintenance immunosuppressive drug. Nine patients were diabetic, and follow-up was between 19 and 37 months. One-year graft and patient survival was 76% and 87%, respectively, Serious complications included four deaths from cardiovascular disorders, and two deaths from viral infections. Studies of peripheral blood T cell subsets showed a prolonged reduction in the absolute number of helper (Leu-3+) cells, and a rapid recovery of cytotoxic/suppressor (Leu-2+) cells. Analysis of the latter subset, using the monoclonal antibody 9.3, showed that the ratio of suppressor/cytotoxic cells was approximately 10:1. The normal ratio is 1:1. The mean mixed leukocyte reaction remained below 30% of the pre-TLI value for 6 months, and approached 80% at two years. Similar kinetics were observed in the proliferative response to mitogens. The results show that maintenance immunosuppressive drug therapy can be reduced after TLI as compared with conventional drug regimens that use prednisone in combination with cyclosporine and/or azathioprine.

Adult↗
PubMed1988

Ifosfamide and mesna: marginally active in patients with advanced carcinoma of the pancreas.

Ifosfamide, an analogue of cyclophosphamide, has therapeutic activity against a wide variety of human malignancies. In a phase II trial in carcinoma of the pancreas, we treated 31 patients who had not received prior chemotherapy with a median ifosfamide dose of 2 g/m2/d (range, 1.5 to 2 g/m2/d) administered intravenously (IV) over one hour for five consecutive days every 3 weeks. 2-mercaptoethane sulphonate (mesna), an acrolein antagonist with known uroendothelial protective properties, was administered IV at a dose of 400 mg/m2 over 15 minutes before the daily dose of ifosfamide and repeated every four hours for two additional doses. Among 30 evaluable patients, one patient achieved a complete remission (26+ months) and another patient had a partial remission (4 months). The median duration of survival of all patients from the start of ifosfamide therapy was only 3 months (range, 1 to 26+ months). Treatments were generally well tolerated. The most common toxic effects included granulocytopenia, nausea and vomiting, malaise, anorexia, and mild hematuria. Mesna offers an adequate protection against uroendothelial injury caused by ifosfamide. Despite the previously reported response rate of greater than 20% at the same or lower doses of ifosfamide in other studies, our data suggest that ifosfamide is only marginally active against cancer of the pancreas and appears to be of minimal value in the treatment of patients with this tumor.

Adult↗