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Biomedical subjects

A Lister

Publications and source records attributed to A Lister.

14 recordsLinked to original sources
PubMed1998

Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study.

Rituximab, a chimeric monoclonal antibody that binds specifically to the CD20 antigen, induced objective responses in 50% of patients with low-grade or follicular B-cell lymphoma. Because most nonfollicular B-cell lymphomas also express the CD20 antigen, we conducted a phase II study to evaluate the efficacy and tolerability of this new agent in patients with more aggressive types of lymphoma. Patients with diffuse large B-cell lymphoma (DLCL), mantle cell lymphoma (MCL), or other intermediate- or high-grade B-cell lymphomas according to the Working Formulation were included in this prospective randomized phase II study if they were in first or second relapse, if they were refractory to initial therapy, if they progressed after a partial response to initial therapy, or if they were elderly (age >60 years) and not previously treated. The patients received 8 weekly infusions of rituximab at the dose of 375 mg/m2 in arm A or one infusion of 375 mg/m2 followed by 7 weekly infusions of 500 mg/m2 in arm B. Patients were evaluated 2 months after the last rituximab infusion. Fifty-four patients were randomized from 9 centers in Europe and Australia (28 in arm A and 26 in arm B). A total of 5 complete responses (CR) and 12 partial responses (PR) were observed among the 54 enrolled patients, with no difference between the two doses. In an intent-to-treat analysis, the CR rate was 9% (CI95%, 3% to 20%) and the PR rate was 22% (CI95%, 12% to 36%), for an overall response rate of 31% (CI95%, 20% to 46%). An analysis of prognostic factors showed that response rates were lower in patients with refractory disease, patients with lymphoma not classified as DLCL, and patients with a tumor larger than 5 cm in diameter. DLCL and MCL patients had response rates of 37% and 33%, respectively. The median time to progression exceeded 246 days for the 17 responding patients. The most frequently reported adverse events were related to an infusion syndrome and were mild: 19% of the patients had a grade 3 related adverse event, slightly more in arm B, and only 1 patient had a grade 4 related adverse event in arm A. Two patients (3.7%) withdrew from treatment because of severe adverse events, one patient in each arm. In this first trial of rituximab in DLCL and MCL, patients experienced a significant clinical activity with a low toxicity. Rituximab has significant activity in DLCL and MCL patients and should be tested in combination with chemotherapy in such patients.

Adult↗
PubMed1997

Absence of toxicity of oats in patients with dermatitis herpetiformis.

BACKGROUND: People with gluten sensitivity should avoid foods containing wheat, rye, and barley, but there has been debate about whether they should avoid oats. Although patients with celiac disease have recently been shown to tolerate oats, less is known about the effects of oats on patients with dermatitis herpetiformis. METHODS: We studied seven men and three women (mean age, 58 years) with biopsy-confirmed dermatitis herpetiformis. They had followed a strict gluten-free diet for a mean of 15.8 years, which controlled their rash and enteropathy. The patients added oats that were not contaminated with gluten to their diets for 12 weeks (mean [+/-SD] daily intake, 62.5+/-10.8 g). RESULTS: None of the patients had any adverse effects. Serologic tests for antigliadin, antireticulin, and antiendomysial antibodies were negative before oats were introduced into the diet and after they were discontinued. Villous architecture remained normal: the mean (+/-SE) ratio of the height of villi to the depth of crypts was 3.59+/-0.11 before the diet and 3.71+/-0.09 afterward (normal, 3 to 5), and the mean enterocyte heights were 31.36+/-0.58 microm and 31.75+/-44 microm, respectively (normal range, 29 to 34). Duodenal intraepithelial lymphocyte counts all remained within normal limits (mean, 13.8+/-1.03 per 100 enterocytes before the diet and 14.2+/-1.2 per 100 enterocytes afterward; normal range, 10 to 30). Dermal IgA showed no significant changes. CONCLUSIONS: Patients with dermatitis herpetiformis can include moderate amounts of oats in their gluten-free diets without deleterious effects to the skin or intestine.

Adult↗
PubMed1995

Mortality of copper cadmium alloy workers with special reference to lung cancer and non-malignant diseases of the respiratory system, 1946-92.

OBJECTIVES: To identify and quantify any relations between occupational exposure to cadmium oxide fume and mortalities from lung cancer and from chronic non-malignant diseases of the respiratory system. METHODS: The mortality experience of 347 copper cadmium alloy workers, 624 workers employed in the vicinity of copper cadmium alloy work (vicinity workers), and 521 iron and brass foundry workers (all men) was investigated for the period 1946-92. All subjects were first employed in these types of work in the period 1922-78 and for a minimum period of one year at one of two participating factories. Two analytical approaches were used, indirect standardisation and Poisson regression. RESULTS: Compared with the general population of England and Wales, mortality from lung cancer among copper cadmium alloy workers was close to expectation (observed deaths 18, expected deaths 17.8, standardised mortality ratio (SMR) 101, 95% confidence interval (95% CI) 60 to 159). A significant excess was shown for lung cancer among vicinity workers but not among iron and brass foundry workers (vicinity workers: observed 55, expected 34.3, SMR 160, 95% CI 121 to 209, P < 0.01; iron and brass foundry workers: observed 19, expected 17.8, SMR 107, 95% CI 64 to 167). Increased SMRs for non-malignant diseases of the respiratory system were shown for each of the three groups (alloy workers: observed 54, expected 23.5, SMR 230, 95% CI 172 to 300, P < 0.001; vicinity workers: observed 71, expected 43.0, SMR 165, 95% CI 129 to 208, P < 0.001; iron and brass foundry workers: observed 34, expected 17.1, SMR 199, 95% CI 137 to 278, P < 0.01). Work histories of the copper cadmium alloy workers were combined with independent assessments of cadmium exposures over time to develop individual estimates of cumulative exposure to cadmium; this being a time dependent variable. Poisson regression was used to investigate risks of lung cancer and risks of chronic non-malignant diseases of the respiratory system in relation to three levels of cumulative cadmium exposure (< 1600, 1600-4799, > or = 4800 micrograms.m-3.y). After adjustment for age, year of starting alloy work, factory, and time from starting alloy work, there was a significant positive trend (P < 0.01) between cumulative exposure to cadmium and risks of mortality from chronic non-malignant diseases of the respiratory system. Relative to a risk of unity for the lowest exposure category, risks were 4.54 (95% CI 1.96 to 10.51) for the middle exposure category and 4.74 (95% CI 1.81 to 12.43) for the highest exposure category. There was a non-significant negative trend between cumulative cadmium exposure and risks of mortality from lung cancer. Relative to a risk of unity for the lowest exposure category, risks were 0.85 (95% CI 0.27 to 2.68) for the middle exposure category and 0.81 (95% CI 0.18 to 3.73) for the highest exposure category. Similar findings were obtained when adjustment was made for age only. CONCLUSIONS: The findings are consistent with the hypothesis that exposure to cadmium oxide fume increases risks of mortality from chronic non-malignant diseases of the respiratory system. The findings do not support the hypothesis that exposure to cadmium oxide fume increases risks of mortality for lung cancer.

Alloys↗
PubMed1994

Resistance to cytosine arabinoside in acute leukemia: the significance of mutations in CTP synthetase.

The molecular events which confer cellular resistance to cytotoxic drugs such as cytosine arabinoside (ara-C) are poorly understood. Nevertheless, in a proportion of patients with acute leukemia, such events will be responsible for the failure of therapy. Mutations which cause ara-C resistance in a chinese hamster ovary (CHO) cell model have been identified as regulatory base substitutions, occurring in specific sites of the gene coding for an enzyme critical in pyrimidine metabolism, CTP synthetase (CTPs). These cells have elevated dCTP pools, a feature common to biochemical studies of other ara-C resistant leukemic cells. A 94% homology exists between the hamster and human ctps genes. In this study, similar mutations were sought in samples taken from 36 patients, with recurrent or resistant acute leukemia. No mutations were identified in the regions indicated by the CHO model using techniques capable of detecting mutations only if present in more than 10% of the cells studied. Thus, mutations in these sites within the human ctps gene do not appear to be a major mechanism of resistance to ara-C in acute leukemia. Further studies should be directed towards developing more sensitive methods of detection, and these then applied both to CTPs and to other enzymes involved in pyrimidine metabolism.

Acute Disease↗
PubMed1983

Homogeneously staining regions and tumorigenicity.

A homogeneously staining region (HSR), a chromosome abnormality associated with gene amplification, was found to increase in length coincident with an enhancement in tumorigenicity when cells from a human retinoblastoma cell line were serially passaged in athymic (nu/nu) mice.

Animals↗