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Biomedical subjects

I Wolff

Publications and source records attributed to I Wolff.

At least 19 recordsLinked to original sources
PubMed2001

Frequency of HPRT mutants in humans exposed to vinyl chloride via an environmental accident.

The mutant frequency (MF) in the hypoxanthine-guanine-phosphoribosyl-transferase (HPRT) locus of peripheral blood T-lymphocytes was measured in a population environmentally exposed to vinyl chloride - a toxic and carcinogenic substance through an accidental release into the atmosphere. It was compared to MF in a control group of unexposed individuals. Both groups were re-investigated in a follow-up study, 2 years later. No significant difference could be observed in MF between exposed and controls either at the accident nor in the follow-up study. Approximately the same mean HPRT mutant frequencies were observed for both groups in T-lymphocytes from blood samples obtained shortly after the accident and from the follow-up blood samples. Both groups showed a higher mean MF in the re-investigation samples which is most probably due to the significantly lower average cloning efficiency (CE) under non-selective conditions and because of the inverse relationship between CE and MF. The exposed population showed a higher mean T-cell CE at the initial blood sampling as compared to the control group. The concurrent cytogenetic analyses of peripheral lymphocytes showed a significant increase in cells with aberrations in the exposed population. Clastogenic but not mutagenic activity of vinyl chloride was observed in our study.

Adult↗
PubMed2000

Phase I and pharmacological study of weekly administration of the polyamine synthesis inhibitor SAM 486A (CGP 48 664) in patients with solid tumors. European Organization for Research and Treatment of Cancer Early Clinical Studies Group.

A single-agent dose-escalating Phase I and pharmacological study of the polyamine synthesis inhibitor SAM 486A was performed. A dosing regimen of four weekly infusions followed by 2 weeks off therapy was studied. Fifty patients were entered into the study. Dose levels studied were 1.25, 2.5, 5, 8, 16, 32, 48, 70, 110, 170, 270, and 325 mg/m2/week. Pharmacokinetic sampling was done on day 1, and trough samples were taken weekly during the first treatment cycle. Pharmacodynamic sampling was done on days 1 and 22. At 325 mg/m2/week, dose-limiting toxicity was seen (one patient each with grade 4 febrile neutropenia, grade 3 neurotoxicity, and grade 3 hypotension with syncope and T-wave inversions on electrocardiogram). The recommended dose for further testing was set at 270 mg/m2/week. Infusion time was increased from 10 to 180 min due to facial paresthesias and flushing and somnolence. Drug exposure increased linearly with dose. Mean +/- SD t1,2 at 70-325 mg/m2 doses was 61.4+/-26.2 h, with a large volume of distribution at steady state. In peripheral blood leukocytes, a clear relationship between dose and inhibitory effect on S-adenosylmethionine decarboxylase or changes in intracellular polyamine pools was not recorded. SAM 486A can be administered safely using a dosing regimen of four weekly infusions followed by 2 weeks off therapy. The recommended dose for Phase II studies using this regimen is 270 mg/m2/week.

Adult↗
PubMed1999

The effect of exercise training programs on bone mass: a meta-analysis of published controlled trials in pre- and postmenopausal women.

With the aging of the population, the medical and social costs of skeletal fragility leading to fractures will cause an immense burden on society unless effective prophylactic and therapeutic regimens can be developed. Exercise is suggested as a possible regimen against involutional bone loss. The purpose of the present meta-analysis is to address a quantitative review of the randomized controlled trials (RCTs) and nonrandomized controlled trials (CTs) on the effects of exercise training programs on bone mass, measured as bone mineral density (BMD) or bone mineral content (BMC), of the lumbar spine (LS) and the femoral neck (FN) in pre- and postmenopausal women. The literature from 1966 through December 1996 was searched for published RCTs and CTs. Study treatment effect is defined as the difference between percentage change in bone mass per year in the training group and the control group. Overall treatment effects (OTs) with the 95% confidence intervals of these study treatment effects were calculated using inverse-variance weighting. Of the 62 articles identified, 25 met the inclusion criteria and were maintained for further analyses. The weighted OTs for the RCTs showed very consistently that the exercise training programs prevented or reversed almost 1% of bone loss per year in both LS and FN for both pre- and postmenopausal women. The two OTs that could be calculated for strength training programs did not reach significance. The OTs for the CTs were almost twice as high as those for the RCTs, which gives an indication of the confounding introduced by the nonrandom allocation of the subjects to groups.

Adult↗
PubMed1999

Physical work capacity after 7 wk of wheelchair training: effect of intensity in able-bodied subjects.

PURPOSE: The purpose of this study was to study the effects of a 7-wk wheelchair training program on physical work capacity in able-bodied subjects. Effects of training intensities of 50 and 70% heart rate (HR) reserve (HRR) were studied for different subject groups. METHODS: Twenty-seven able-bodied male subjects participated in this study. They were randomly divided into a control group (N = 8), a 50%-intensity group (N = 9), and a 70%-intensity group (N = 10). The 50%- and the 70%-intensity groups received a 7-wk wheelchair training program: three times a week, one-half hour wheelchair exercise on a motor driven treadmill at an average intensity of 50 and 70% of the HRR, respectively. Before and after the training period, parameters for physical work capacity (maximal isometric strength (Fiso), sprint power (P30), maximal power output (POmax) and peak oxygen uptake (VO2peak)), and submaximal performance (mechanical efficiency, HR) at 20 and 40% of the estimated POmax (ME20, ME40; HR20, HR40) were obtained during tests on a stationary wheelchair ergometer. RESULTS: A two-factor ANOVA for repeated measures on the within-subjects factor "pre-post tests," the between-subject factor training (50% and 70% training vs control) and the interaction term showed that the 50%-intensity group significantly increased on P30 and POmax compared with the control group. The 70% intensity group significantly increased on P30, POmax and VO2peak compared with the control group (P < 0.05). The 70% group did not show significantly higher increases in P30 and POmax over training than the 50% intensity. No significant effects were found for the Fiso and the parameters at submaximal PO. CONCLUSIONS: The wheelchair training at both intensities can have favorable effects on maximal physical work capacity in able-bodied subjects, and possibly also on mechanical efficiency at submaximal power output. Effects are seen in parameters for both aerobic and anaerobic work capacities. Although training at 70% intensity was more effective than the 50% intensity, training at 50% HRR may initially be more appropriate in untrained individuals, such as novice wheelchair users at the start of their rehabilitation, to prevent fatigue and enhance motivation.

Adult↗
PubMed1996

EO9 phase II study in advanced breast, gastric, pancreatic and colorectal carcinoma by the EORTC Early Clinical Studies Group.

In a phase II trial, the activity of EO9, a new bioreductive alkylating agent, was assessed. EO9 was used as second-line chemotherapy in breast cancer patients and as first-line chemotherapy for patients with gastric, pancreatic and colorectal cancer. EO9 was given as a 5 min i.v. infusion at a weekly dose of 12 mg/m2. 92 patients were entered; 22 with breast cancer, 26 with colon cancer, 24 with pancreatic cancer and 20 with gastric cancer. In general, the drug was well tolerated with nausea and vomiting occurring in 26.42 and 13.3% of courses, respectively. Reversible proteinuria was the main toxicity occurring in 45% of courses. Antitumour activity was not observed. At this dose and schedule, EO9 is not an active drug in the type of tumour studied.

Adult↗
PubMed1996

Phase I clinical and pharmacokinetic study of carzelesin (U-80244) given daily for five consecutive days.

Carzelesin (U-80244), one of the synthetic DNA minor groove binding cyclopropylpyrroloindole analogues, was selected for clinical development because of its high potency, promising antitumor activity in murine solid tumors and leukemia, and significant therapeutic efficacy against colon and rhabdomyosarcoma xenografts. In this Phase I study, carzelesin was given daily for 5 consecutive days to (a) determine the maximum tolerable dose (MTD) and the pattern of toxicity of this schedule; (b) define the pharmacokinetic profile of the parent, as was done for the intermediate compound U-76073 and the DNA-reactive agent U-76074; and (c) document any antitumor activity observed. Carzelesin was given as a 10-min infusion with a constant-rate infusion pump. Treatment was repeated every 4 weeks or when blood counts had recovered to normal values. The starting dose of 12 microgram/m2/day was escalated by 20-30% increments until the MTD (defined as the dose leading to grade 4 hematological or grade 3 nonhematological toxicity in at least two of six patients) was reached. Pharmacokinetic studies were planned on days 1 and 5 of the first cycle in at least two patients per dose level. Plasma levels of carzelesin, U-76073, and U-76074 were determined by high-performance liquid chromatography with UV detection and a detection limit of 0.5 ng/ml. Twenty-five patients were entered in the study, and 56 cycles were evaluable for hematological toxicity. Subsequent dose levels evaluated were 24, 30, 35, and 40 microgram/m2. Both neutropenia and thrombocytopenia were dose limiting and cumulative, with a high interpatient variability. Neutropenia occurred earlier (median time to neutrophil nadir and recovery, 15 and 29 days, respectively) than thrombocytopenia (median time to platelet nadir and recovery, 25 and >/=26 days, respectively); there were delays of treatment because of persisting thrombocytopenia in all patients treated at the MTD. At the MTD, the peak plasma concentrations of carzelesin were achieved at the end of the infusion and were higher than those found cytotoxic in vitro against tumor cell lines. Carzelesin was detectable up to a maximum of 1 h after the infusion. Smaller amounts of U-76073 were detectable for a maximum of 30 min only at the MTD, whereas U-76074 was never found. An 8-month partial remission was reported in one previously untreated patient with hepatocellular carcinoma at 40 microgram/m2. The MTD was fixed at 40 microgram/m2 daily; 35 and 30 microgram/m2 are the daily doses recommended for Phase II studies in good- and poor-risk patients. The daily regimen for 5 days seems to offer no advantage over the single intermittent schedule that has been selected for the Phase II program in Europe.

Adult↗
PubMed1995

Phase II studies of docetaxel in the treatment of various solid tumours. EORTC Early Clinical Trials Group and the EORTC Soft Tissue and Bone Sarcoma Group.

Docetaxel has been evaluated in six tumour types in a total of 189 patients entered into phase II studies. Treatment consisted of a 1 h intravenous infusion of docetaxel 100 mg/m2 repeated every 3 weeks. No premedication was administered for possible hypersensitivity reactions. Docetaxel was found to be effective as first-line chemotherapy for head and neck cancer (response rate 44%) gastric cancer (23%) and melanoma (14%) and as second-line chemotherapy for soft tissue sarcomas (21%; 95% confidence interval: 7.5%-43.7%). The results in colorectal and renal cancer were disappointing, with response rates of less than 10%. The most frequent adverse effects were alopecia (81%), grade III-IV leukocytopenia of short duration (66%) and skin reactions (52%). Hypersensitivity reactions were mild and occurred in 26% of patients. Docetaxel is an important new drug in the treatment of solid tumours.

Antineoplastic Agents, Phytogenic↗
PubMed1994

Docetaxel (Taxotere) in advanced malignant melanoma: a phase II study of the EORTC Early Clinical Trials Group.

The antitumour activity of docetaxel was investigated in patients with advanced malignant melanoma. Docetaxel, 100 mg/m2, intravenous, over 60 min, was administered every 3 weeks. Response evaluation was performed after two cycles. No prophylactic treatment with steroids or antihistamines was given. 38 patients were included, 36 were eligible and evaluable for toxicity and 30 patients were evaluable for response. The main haematological toxicity was neutropenia [17 patients with common toxicity criteria (CTC) grade 4 and 11 CTC grade 3] with nadir after 5-8 days and rapid recovery. The most frequent non-haematological toxicity was generalised alopecia (83% of the patients). Asthenia, malaise and fatigue were also seen in 58%. Skin toxicity was also frequent. Hypersensitivity reactions (erythematous rash, urticaria, blood pressure changes and tachycardia), seen in 42% of the patients, were mild to moderate. Oedema was registered in one fifth of the patients and developed after four or more treatment cycles. The overall response rate in the evaluable patients was 17% (five partial responders). We conclude that docetaxel has activity in advanced malignant melanoma.

Adult↗
PubMed1994

Gemcitabine in patients with advanced malignant melanoma or gastric cancer: phase II studies of the EORTC Early Clinical Trials Group.

BACKGROUND: Gemcitabine is a water-soluble analogue of deoxycytidine which has shown significant antitumour activity in a broad panel of slow-growing murine and human carcinomas. Objective responses have been reported in early clinical studies in breast, head and neck, non-small cell lung cancer patients. The weekly schedule was selected for disease-oriented phase II studies because of its better tolerability as compared to daily or twice-weekly schemes. PATIENTS AND METHODS: Gemcitabine (1000 mg/m2) was given as a 30 min. infusion, weekly for three consecutive weeks, followed by one-week rest, every 4 weeks. Twenty-nine patients with locally advanced/metastatic gastric cancer and 39 patients with metastatic malignant melanoma entered the study. No prior chemotherapy for advanced disease had been given in all cases. RESULTS: Among 26 evaluable patients with gastric cancer, 1 partial response (PR) of 9 months (4%), 11 no change (NC) and 14 tumour progression (PD) were observed. Of 33 evaluable patients with malignant melanoma, 1 patient achieved a PR for 10 months (3%), 2 had NC and 30 PD. Toxicity was similar in the two groups with moderate myelosuppression, mainly neutropenia, mild to moderate nausea and vomiting in 70% of patients and fatigue grade 1-2 in 50%. CONCLUSIONS: At the tested schedule gemcitabine has no relevant antitumour activity in previously untreated patients with advanced malignant melanoma or gastric cancer.

Adenocarcinoma↗
PubMed1992

Health hazards in the semiconductor industry. A review.

The development of semiconductor production has been accompanied by an increased use of toxic production materials and an increased release of potential toxic wastes, which are harmful to health and environment. This paper gives an overview of occupational health hazards resulting from production materials in the microelectronics industry and from waste products originating as gases from plasma etching processes in photolithography during semiconductor production. The paper proposes methods for using experimental toxicology to investigate the occupational risks from complex mixtures of chemicals in the semiconductor industry.

Hazardous Substances↗
PubMed1990

Allergic and nonallergic rhinitis: their characterization in a tropical environment.

The differences between allergic and non-allergic rhinitis were evaluated in 127 individuals from tropical urban region of Venezuela. The study design had historic data obtained regarding exacerbation of initial symptoms on exposure to common precipitants, physical examination, nasal cytology, immunodiagnostic test, routine laboratory test (fresh stool test, white cell count and urine test) and sinus x-rays. Forty nine patients were diagnosed as having allergic rhinitis (AR), 10 as probably having AR, 13 had infectious rhinitis, 4 had mixed components, 1 as non-allergic non-eosinophilic rhinitis, and 50 had no evidence of immunological nasal respiratory allergy and were taken as controls. The associated findings with allergic rhinitis were: conjunctivitis 62%, sinusitis 23%, and bronchial asthma 24%. Our results support a significative prevalence of allergic rhinitis in this particular group, with similar symptom patterns to that of industrialized countries.

Adolescent↗
PubMed1981

Isolation of dominant suppressor mutations for position-effect variegation in Drosophila melanogaster.

Dominant suppressor mutations for position-effect variegation have been isolated by using a strongly variegated line carrying the wm4 chromosome (wm4h) and the dominant enhancer mutant En(var)c101. The use of an effective genetic test system made it possible to isolate more than 100 strongly dominant suppressor mutations for position-effect variegation. This suggests that the phenomenon of position-effect variegation is characterised by a complex genetic basis. The significance of the isolated mutants to genetic dissection of structural and regulatory functions of the eukaryotic chromosome is discussed.

Animals↗
PubMed1980

[Drug distribution during convulsive seizure in comparison with narcosis].

3 min after simultaneous i.v. administration of phenazone (200 mg/kg) and of pentetrazole (50 mg/kg) or of phenazone and of the convulsively active S-(+)-1-methyl-5-phenyl-5-propyl barbituric acid = (+)-MPPB (75 mg/kg), respectively, phenazone concentrations in liver, spleen and fat tissue of rats are lower, in brain tissue, however, it is higher than those of the control (rats receiving phenazone only); the distribution pattern of (+)-MPPB between the tissues corresponds to that of phenazone after simultaneous administration of pentetrazole. In rats anaesthetized by hexobarbital (35 mg/kg) or by the anaesthetically active R-(-)- 1-methyl-5-phenyl-5-propyl barbituric acid = (-)-MPPB (75 mg/kg), respectively, phenazone tissue distribution is at the same time (3 min) not different from that of the control; the tissue distribution pattern of (-)-MPPB corresponds to that of phenazone after simultaneous administration of hexobarbital. Following pretreatment with diazepam, reserpine and phenoxybenzamine, respectively, the tissue distribution pattern of (+)-MPPB, in the rats approaches that of (-)-MPPB. The distribution of (-)-MPPB in the tissues corresponds to that of (+)-MPPB, if the animals receive simultaneously pentetrazole or are electrically stimulated, respectively, to cause a convulsive seizure.

Adipose Tissue↗