Showing papers by "Bethesda Hospital published in 2003"

Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial.

Abstract: . Wulffele MG, Kooy A, Lehert P, Bets D, Ogterop JC, Borger van der Burg B, Donker AJM, Stehouwer CDA (Bethesda General Hospital, Hoogeveen, The Netherlands; University of Mons, Mons, Belgium; Merck Nederland B.V., Amsterdam; Deaconesses’ Hospital, Meppel; Aleida Kramer Hospital, Coevorden; and Vrije Universiteit Medical Centre, Amsterdam; The Netherlands). Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med 2003; 254: 455–463. Objective. Metformin is a key treatment option in type 2 diabetes. However, metformin may decrease vitamin B12 levels and increase levels of homo-cysteine, a cardiovascular risk factor. We investigated whether 16 weeks of treatment with metformin affects serum concentrations of homo-cysteine, folate and vitamin B12 in subjects with type 2 diabetes treated with insulin. Design. Placebo-controlled, randomized trial. Measurements: at baseline and 16 weeks later. Setting. This trial was conducted in the outpatient clinics of three general hospitals in The Netherlands. Subjects. A total of 745 patients with type 2 diabetes, treated with insulin and not known with a contraindication for the use of metformin, were approached; 390 gave informed consent and entered the study. Thirty-seven subjects dropped out (12 placebo and 25 metformin users). Intervention. Addition of metformin or placebo to insulin therapy. Primary outcome parameters. Serum homocysteine, folate, vitamin B12, indices of glycaemic control and body weight. Results. Amongst those who completed 16 weeks of treatment, metformin use, as compared with placebo, was associated with an increase in homocysteine of 4% (0.2 to 8; P = 0.039) and with decreases in folate [−7% (−1.4 to −13); P = 0.024] and vitamin B12 [−14% (−4.2 to −24); P < 0.0001]. In addition, the increase in homocysteine could be explained by the decreases in folate and vitamin B12. Conclusion. In patients with type 2 diabetes, 16 weeks of treatment with metformin reduces levels of folate and vitamin B12, which results in a modest increase in homocysteine. The clinical significance of these findings remains to be investigated.

First-line gemcitabine with cisplatin or epirubicin in advanced non-small-cell lung cancer: a phase III trial

Abstract: The purpose of our study was to compare progression-free survival and quality of life (QOL) after cisplatin–gemcitabine (CG) or epirubicin–gemcitabine (EG) in chemotherapy-naive patients with unresectable non-small-cell lung cancer. Patients (n=240) were randomised to receive gemcitabine 1125 mg m−2 (days 1 and 8) plus either cisplatin 80 mg m−2 (day 2) or epirubicin 100 mg m−2 (day 1) every 3 weeks for a maximum of five cycles. Eligible patients had normal organ functions and Eastern Cooperative Oncology Group performance status ⩽2. QOL was measured with European Organisation for Research and Treatment of Cancer QLQ-C30 and LC13 questionnaires. There were no significant differences in median progression-free survival (CG 26 weeks, EG 23 weeks), median overall survival (CG 43 weeks, EG 36 weeks), or tumour response rates (CG 46%, EG 36%). Toxicity was mainly haematologic. In the EG arm granulocytopenia occurred more frequently, leading to more febrile neutropenia. Also, elevation of serum transaminases, mucositis, fever, and decline in LVEF were more common in the EG arm. In the CG arm, more patients experienced elevated serum creatinine levels, sensory neuropathy, nausea, and vomiting. Global QOL was not different in both arms. Progression-free survival, overall survival, response rate, and QOL were not different between both arms; however, overall toxicity was more severe in the EG arm.

Molecular patchwork: Chromosomal recombination between two Helicobacter pylori strains during natural colonization

Abstract: Genetic analysis of two Helicobacter pylori strains isolated from a single gastric biopsy showed evidence of extensive horizontal gene transfer. Several large recombinations were identified in the rdxA gene, which is involved in metronidazole resistance.

Extensive hepatic replacement due to liver metastases has no effect on 5-fluorouracil pharmacokinetics.

Abstract: Purpose. The influence of liver metastases on the pharmacokinetics of 5-fluorouracil (5-FU) and its metabolite 5,6-dihydrofluorouracil (DHFU) was studied in patients with liver metastases from gastrointestinal cancer (n=16) and compared with a control group of patients with nonmetastatic gastrointestinal cancer (n=18). Methods. Patients were assigned to two different groups based on the presence of liver metastases. The percentage of hepatic replacement was determined with CT and ultrasonography and classified as 50% of the total liver volume. Chemotherapy consisted of leucovorin 20 mg/m2 per day plus 5-FU 425 mg/m2 per day, both for 5 days. Blood sampling was carried out on the first day of the first chemotherapy cycle. 5-FU and DHFU were quantified in plasma by HPLC. A four-compartment parent drug-metabolite model with nonlinear Michaelis-Menten elimination from the central compartment of the parent drug (5-FU) was applied to describe 5-FU and DHFU pharmacokinetics. Results. No effect of liver metastases on 5-FU clearance was observed. The effects of 18 covariables on pharmacokinetic parameters were also studied in a univariate correlation analysis. Body surface area was positively correlated with the distribution volume of 5-FU in the central compartment and with Vmax (r=0.65 and r=0.54, respectively). Conclusions. There is no need for dose adjustment of 5-FU as a standard procedure in patients with liver metastases and mild to moderate elevations in liver function tests.

Dyspepsia management in primary care.

Abstract: Background: Dyspepsia is common in western society. Prompt endoscopy is imperative in all patients with sinister symptoms or if symptoms first appear after the age of 50-55 years, but the optimal management of younger patients with uncomplicated dyspepsia is still open to debate. Methods: The literature on the management of uncomplicated dyspepsia is reviewed and a personal view is presented. Results: Strategies based on non-invasive detection of Helicobacter pylori are probably the most cost-effective. Currently (H. pylori prevalence 30%-40%), a 'test and treat' approach using a non-invasive test to detect H. pylori is likely to be the most efficient first step. If the patient is H. pylori-negative or if symptoms persist after successful H. pylori eradication, empirical treatment with an anti-secretory drug is justified. Endoscopy is reserved for those patients in whom this approach fails. If the prevalence of H. pylori decreases, the positive predictive value of any non-invasive H. pylori test will become too low. A 'test and scope' approach in which a positive test can be confirmed by two or more biopsy-based tests is then more appropriate. At a very low prevalence of H. Pylori in the dyspeptic population, non-invasive testing for H. pylori loses its significance and empirical treatment with an antisecretory drug becomes a rational first step. Conclusions: The optimal approach to management of uncomplicated dyspepsia is dependent on the prevalence of H. pylori among the dyspeptic population. At the current prevalence rate, 'test and treat', followed by acid suppressive treatment in the case of persisting symptoms, is the most appropriate strategy.

The Use of a Diagnostic Database in Clinical Oncogenetics

Abstract: In addition to a relatively small number of well known hereditary cancer syndromes, hundreds of presumed or proven hereditary disorders have been observed to manifest cancer as a characteristic feature or as a possible complication. The recognition of these disorders may be of great importance for the medical management of the families involved. Specialized databases, like the Familial Cancer Database (FaCD, http://www.facd.info), may be helpful in the making of differential diagnoses and offer advantages compared with traditional textbooks and on-line literature searches. Based on our own experience and interviews with the other Dutch family cancer clinics, we expect that in similar clinics, computer-assisted differential diagnosis will be primarily used in helping to decide whether or not cancer patients and families should be referred to family cancer clinics for further study and counseling. FaCD has been developed as a tool for experts. As general practitioners and other health professionals with non-expert knowledge of cancer genetics are under increasing pressure to advise on genetic risks, it should be encouraged that other software is developed to support them in interpreting family histories of cancer.

Mechanisms of death in the early postoperative period following coronary artery bypass grafting for acquired heart disease. A clinicopathological study of 32 cases.

Abstract: A retrospective cardiopathological and clinical study was conducted in order to determine causes of perioperative death following coronary artery bypass grafting (CABG). Between January 1992 and June 1995, a total of 5749 CABG procedures were performed at the Heart Center Duisburg (Germany). Following the procedures, 218 patients died in hospital (mortality rate 3.8%). Fifty-eight were autopsied at the Institute of Pathology, Bethesda Hospital, Duisburg, and 32 autopsied cases were amenable to our study. Basis for selection was accessibility of clinical and morphological data and a postoperative death within 30 days. In each case, morphological analysis of the heart and an evaluation of surgical and clinical data were performed in order to draw a conclusion on the mechanism of death. Using criteria defined by us, the following causes of death were determined: (1) surgical complications (43%); (2) severe coronary artery disease with incomplete revascularization (41%); (3) congestive heart failure (13%); (4) non-cardiac complications (3%). Criteria defined in this study may be useful in evaluations of causes of death after open heart surgery and may help to compare results in future series. Determination of the cause of death is important for the cardiac surgeon to reconsider indications and quality of surgical procedure.