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Biomedical subjects

A B Weitberg

Publications and source records attributed to A B Weitberg.

At least 37 records · Page 2Linked to original sources
PubMed1989

Age as a predictor of diagnostic and initial treatment intensity in newly diagnosed breast cancer patients.

Newly diagnosed breast cancer patients (N = 494) aged 45-90 years were studied to determine if age was associated with appropriate diagnostic and prognostic evaluations, and initial definitive therapy. Women 75 years of age and older were less likely to receive an appropriate diagnostic evaluation than were younger women, but age was not associated with an appropriate prognostic evaluation. Older patients with local disease who were undergoing lumpectomy were less likely to receive follow-up radiation; older patients with regional disease undergoing mastectomy were less likely to receive adjuvant chemotherapy (including hormonal therapy). Physicians' attitudes about appropriateness of therapy appear to be the major determinant of what treatment is received.

Age Factors↗
PubMed1989

A phase I/II trial of 5-fluorouracil and etoposide in metastatic colorectal carcinoma.

Twenty-two patients with metastatic colorectal carcinoma were treated in a Phase I-II study of combination therapy with 5-fluorouracil (5-FU) and etoposide (VP-16). Treatment consisted of weekly intravenous VP-16, 100-120 mg/M2, followed by 5-FU, 400-480 mg/M2, in 28-day cycles. Myelosuppression was the dose-limiting toxicity with a mean nadir leukocyte count of 3,600/mm3 and a mean nadir thrombocyte count of 101,000/mm3. There were no episodes of sepsis or bleeding. The tolerable dose for this regimen is VP-16, 110 mg/M2, and 5-FU, 440 mg/M2, weekly. A total of 63 cycles of chemotherapy were given. Although 10 patients had stabilization of disease, no partial or complete responses were documented. We conclude that there is no clinical support for the in vitro synergy observed with this combination. Further trials of this combination using this schedule in colorectal carcinoma are not indicated.

Adenocarcinoma↗
PubMed1989

Non-ionizing electromagnetic radiation and cancer--is there a relationship?

A number of problems become evident when we attempt to assess the data in this review. We must first acknowledge the fact that EM radiation, as opposed to some chemical and physical pollutants which can be seen, tasted, or detected by odor, is in most situations not detected by human senses. This fact alone, however, does not prove or disprove the conjecture that EMR is a potential health hazard. The studies on the effects of EMR on cell systems, animals, and human subjects, report results which promote in some and reject in others the hypothesis that EMR in the ELF and microwave range is carcinogenic. Much of the criticism of the studies on human subjects centers around (1) quantifying exposure to EM Fields; (2) the epidemiologic-statistical methods used to gather, study, and interpret the data; and (3) lack of data studying co-carcinogens. Although there is no convincing evidence that EMR is carcinogenic, the uncertainty, in addition to the ubiquity of EMR, makes study of its possible health effects and its carcinogenic potential an essential part of future medical and epidemiologic research.

Animals↗
PubMed1989

The effect of alkaline phosphatase on platelet aggregation.

Elevated concentrations of alkaline phosphatase occur in a variety of diseases. The effect of alkaline phosphatase on platelet aggregation was tested. Adenosine diphosphate-induced aggregation was inhibited at the highest concentrations of alkaline phosphatase employed. Similar results were observed when epinephrine, collagen and arachidonic acid were used as aggregating agents. A dose-dependent inhibition of ristocetin-induced aggregation by alkaline phosphatase was observed. These results were confirmed using plasma from patients with cholestatic disease and elevated concentrations of alkaline phosphatase similar to those used in the in vitro studies. These data indicate that patients with significantly elevated levels of alkaline phosphatase may be predisposed to a thrombocytopathy.

Adenosine Diphosphate↗
PubMed1988

Phase I trial of the combination of 6-methylmercaptopurine riboside and 5-fluorouracil.

6-Methylmercaptopurine riboside (MMPR) and 5-fluorouracil (5-FU) were administered sequentially to 12 patients in a phase I clinical trial. Toxicities included mild nausea and vomiting, as well as reversible leukopenia and thrombocytopenia. Maximal accumulation of 6-methylmercaptopurine ribonucleoside 5'-monophosphate (MMPR-P), the active metabolite of MMPR, in patients' erythrocytes occurred between 2 and 6 h after the administration of MMPR and the degree of accumulation was dose-related. At 96 h after MMPR administration, MMPR-P was still detectable in patients' erythrocytes. Although no clinical responses were documented, a modified dosage schedule of these drugs should be pursued based on the pharmacokinetic data obtained.

Aged↗
PubMed1988

Effects of arachidonic acid and inhibitors of arachidonic acid metabolism on phagocyte-induced sister chromatid exchanges.

Stimulated human phagocytes produce toxic oxygen radicals which induce sister chromatid exchanges in cultured mammalian cells. Oxidative damage to membranes initiates lipid peroxidation chain reactions and stimulation of the arachidonic acid cascade. The products of these reactions may mediate the genetic toxicity of oxygen radicals. Arachidonic acid significantly augmented the number of sister chromatid exchanges in target cells exposed to stimulated phagocytes. This genetic damage was abrogated in radical-treated cells preincubated with inhibitors of the cyclooxygenase (indomethacin), lipoxygenase (nordihydroguaiaretic acid) or both (piroxicam) pathways.

Arachidonic Acids↗
PubMed1987

A phase I trial of continuous infusion cisplatin.

Treatment with continuous infusions of cisplatin results in increased filterable drug exposures as measured by the area under the curve (AUC) of nonprotein-bound plasma platinum levels. To determine the dose-limiting toxicity and optimal method of administration, 24 patients were treated with continuous infusions of cisplatin at a dose rate of 25 mg/M2/day in a limited Phase I trial. A total of 47 courses were given. Nine patients received 13 courses of 4 days duration, 19 received 29 courses of 5 days duration, and five received courses of 6 or 7 days duration. Dose-limiting toxicity was found to be leukopenia: 42% of patients receiving the 5-day treatment developed a nadir count of less than 3000 cells/mm3. Nausea and vomiting were easily controlled. Minimal nephrotoxicity occurred in five patients and was associated with daily volume expansion with 2 l of 0.9% NaCl solution in four patients. All other patients were given 3 l of daily volume expansion during treatment. Responses were seen in 6 of 22 evaluable patients (27%). It is concluded that continuous infusion cisplatin at a dose rate of 25 mg/M2/day can be given safely for 5 days as a single agent if concomitant volume expansion with at least 3 l of 0.9% NaCl solution is given daily. Phase III comparative trials with a conventional bolus and newer high-dose regimens for response and toxicity are indicated.

Adult↗
PubMed1987

Chloramine-induced sister-chromatid exchanges.

Nitrogen-chlorine (N-Cl) derivatives are a class of long-lived oxidants produced by stimulated phagocytes which may be important mediators of the inflammatory response. Because other phagocyte-generated oxidants cause genetic damage in cultured mammalian cells, we studied the ability of the synthetic N-Cl compound, chloramine T (Cl-T), to produce sister-chromatid exchanges (SCEs) in cultured Chinese hamster ovary (CHO) cells. CHO cells were incubated for 30 h with Cl-T (10(-8) M-10(-5) M) and genetic damage was analyzed utilizing the SCE assay. A significant (p less than 0.0005) dose-dependent increase in SCEs was observed. This effect was diminished when cells were treated concomitantly with methionine (10(-5) M), a thioether which reduces N-Cl back to the parent amine. Extracellularly-generated oxidants must traverse long distances before interacting with nuclear target molecules. Therefore, long-lived N-Cl derivatives may represent an important class of oxidants which mediate the process of carcinogenesis associated with chronic inflammatory states in vivo.

Animals↗
PubMed1987

Antioxidants inhibit the effect of vitamin C on oxygen radical-induced sister-chromatid exchanges.

The mechanism of vitamin C-induced sister-chromatid exchanges in cultured mammalian cells was studied. Chinese hamster ovary cells, when exposed to an enzymatic oxygen radical-generating system (xanthine oxidase plus hypoxanthine), develop increased numbers of sister-chromatid exchanges. Inclusion of ascorbate (greater than or equal to 0.1 mM) in these incubations resulted in an augmentation of this effect. Superoxide dismutase (100 microliter/ml) and catalase (220 microliter/ml) caused a significant reduction in the number of sister-chromatid exchanges induced by xanthine oxidase, hypoxanthine and vitamin C. Their heat-inactivated counterparts had no effect. These results confirm that vitamin C (greater than or equal to 0.1 mM) potentiates the genetic toxicity of oxygen radicals and that this effect is mediated by toxic oxygen intermediates.

Animals↗
PubMed1987

Effects of inhibitors of arachidonic acid metabolism and vitamin E on oxygen radical-induced sister chromatid exchanges.

Oxidative damage to membranes initiates lipid peroxidation chain reactions and stimulation of the arachidonic acid cascade. The products of these reactions may mediate the genetic toxicity of oxygen radicals. Arachidonic acid alone induced sister chromatid exchange (SCE) formation and significantly augmented the genetic damage observed with an oxygen radical-generating system. The number of SCEs was reduced significantly in oxygen radical-treated Chinese hamster ovary cells incubated with inhibitors of the cyclo-oxygenase and lipoxygenase pathways. Vitamin E, when combined with inhibitors of arachidonic acid metabolism, protected target cells completely from oxygen radical-induced genotoxicity. These data support the hypothesis that lipid peroxidation intermediates may be involved in the genesis of radical-generated genetic lesions.

Animals↗
PubMed1987

Continuous-infusion cisplatin and bolus 5-fluorouracil in colorectal carcinoma.

Twenty-one evaluable patients with metastatic colorectal carcinoma were treated with a combination of continuous-infusion cisplatin (25 mg/m2/day X 3 days) and bolus 5-fluorouracil (400 mg/m2/day X 3 days). Toxicity was minimal. Seven patients (33%) responded. All responses were observed among the 16 previously untreated patients (44%) and lasted a median of 30 weeks. The results indicate the need for phase III trials of this treatment.

Adult↗