E. G. Hahn

The Virtual Family—development of surface-based anatomical models of two adults and two children for dosimetric simulations

The objective of this study was to develop anatomically correct whole body human models of an adult male (34 years old), an adult female (26 years old) and two children (an 11-year-old girl and a six-year-old boy) for the optimized evaluation of electromagnetic exposure. These four models are referred to as the Virtual Family. They are based on high resolution magnetic resonance (MR) images of healthy volunteers. More than 80 different tissue types were distinguished during the segmentation. To improve the accuracy and the effectiveness of the segmentation, a novel semi-automated tool was used to analyze and segment the data. All tissues and organs were reconstructed as three-dimensional (3D) unstructured triangulated surface objects, yielding high precision images of individual features of the body. This greatly enhances the meshing flexibility and the accuracy with respect to thin tissue layers and small organs in comparison with the traditional voxel-based representation of anatomical models. Conformal computational techniques were also applied. The techniques and tools developed in this study can be used to more effectively develop future models and further improve the accuracy of the models for various applications. For research purposes, the four models are provided for free to the scientific community.

The Effect of Continuous Positive Airway Pressure Treatment on Insulin Sensitivity in Patients with Obstructive Sleep Apnoea Syndrome and Type 2 Diabetes

Background: The obstructive sleep apnoea syndrome (OSA) is a frequent condition, as well as type 2 diabetes mellitus. Both diseases are characterized by insulin resistance. Objectives: The aim of this study was to establish whether OSA is an independent risk factor for increased insulin resistance in diabetics. For this purpose, we tested the hypothesis that the insulin sensitivity in patients with type 2 diabetes and OSA can be improved by 2 days or 3 months of continuous positive airway pressure (CPAP) treatment. Methods: In 9 obese patients with type 2 diabetes and OSA [apnoea/hypopnoea index 43.1 ± 21.3; body mass index (BMI) 37.3 ± 5.6 kg/m2] and good glycaemic control on oral antidiabetics or on diet alone (HbA1c 6.4 ± 0.7%), the insulin sensitivity index (ISI) was established by euglycaemic hyperinsulinaemic clamp tests at baseline, after 2 days and after 3 months of effective CPAP treatment. Results: ISI was unchanged after 2 days of CPAP treatment, but was significantly improved after 3 months (4.38 ± 2.94 vs. 2.74 ± 2.25 at baseline; p = 0.021), without any significant changes in BMI. Glycaemic control was unaffected after 3 months (HbA1c 6.3 ± 0.6%; not significant). Fasting leptin levels showed no significant changes. Conclusions: These results indicate that OSA itself is an independent risk factor for insulin resistance. This effect may be explained by the elevated sympathetic activity in OSA.

Incidence and costs of adverse drug reactions during hospitalisation: computerised monitoring versus stimulated spontaneous reporting.

AbstractObjective: To implement a computer-based adverse drug reaction monitoring system and compare its results with those of stimulated spontaneous reporting, and to assess the excess lengths of stay and costs of patients with verified adverse drug reactions. Design: A prospective cohort study was used to assess the efficacy of computer-based monitoring, and case-matching was used to assess excess length of stay and costs. Setting: This was a study of all patients admitted to a medical ward of a university hospital in Germany between June and December 1997. Patients and participants: 379 patients were included, most of whom had infectious, gastrointestinal or liver diseases, or sleep apnoea syndrome. Patients admitted because of adverse drug reactions were excluded. Methods: All automatically generated laboratory signals and reports were evaluated by a team consisting of a clinical pharmacologist, a clinician and a pharmacist for their likelihood of being an adverse drug reaction. They were classified by severity and causality. For verified adverse drug reactions, control patients with similar primary diagnosis, age, gender and time of admission but without adverse drug reactions were matched to the cases in order to assess the excess length of hospitalisation caused by an adverse drug reaction. Results: Adverse drug reactions were detected in 12% of patients by the computer-based monitoring system and stimulated spontaneous reporting together (46 adverse reactions in 45 patients) during 1718 treatment days. Computer-based monitoring identified adverse drug reactions in 34 cases, and stimulated spontaneous reporting in 17 cases. Only 5 adverse drug reactions were detected by both methods. The relative sensitivity of computer-based monitoring was 74% (relative specificity 75%), and that of stimulated spontaneous reporting was 37% (relative specificity 98%). All 3 serious adverse drug reactions were detected by computer-based monitoring, but only 2 out of the 3 were detected by stimulated spontaneous reporting. The percentage of automatically generated laboratory signals associated with an adverse drug reaction (positive predictive value) was 13%. The mean excess length of stay was 3.5 days per adverse drug reaction. 48% of adverse reactions were predictable and detected solely by computer-based monitoring. Therefore, the potential for savings on this ward from the introduction of computer-based monitoring can be calculated as EUR56 200/year (

The histone-deacetylase inhibitor Trichostatin A blocks proliferation and triggers apoptotic programs in hepatoma cells

US59 600/year) [1999 values]. Conclusion: Computer monitoring is an effective method for improving the detection of adverse drug reactions in inpatients. The excess length of stay and costs caused by adverse drug reactions are substantial and might be considerably reduced by earlier detection.

Diagnostic accuracy of forceps biopsy versus polypectomy for gastric polyps: a prospective multicentre study

BACKGROUND/AIMS Effective treatment for hepatocellular carcinoma is urgently needed. The histone-deacetylase inhibitor Trichostatin A (TSA) was shown to induce apoptosis in non-hepatic cells at submicromolar concentrations. However, the effect of TSA on hepatoma cells is unknown. METHODS The hepatoma cells HepG2, MH1C1, Hepa1-6 and Hep1B as well as human fibroblasts (control cells) were exposed to TSA (10(-6) to 10(-9)M). Cell proliferation was assessed by measuring DNA-synthesis and cell numbers. Apoptosis was quantified by flow cytometry and by the TdT-mediated dUTP nick-end labeling method. Expression patterns of cell cycle- and/or apoptosis-associated p27, p21(cip/waf), bax, bcl-2, cyclin A and (pro)-caspase 3 were studied using quantitative Western blotting. Activation of caspase 3 was analyzed via a colorimetric assay. RESULTS 10(-6)M TSA inhibited DNA-synthesis by 46% (HepG2) to 64% (MH1C1) after 24h, inducing a G(2)/M-phase arrest and apoptosis. TSA increased activation of caspase 3 and expression of cyclin A, p2l(cip/waf), bax and (pro)-caspase 3, while bcl-2 was downregulated. Human fibroblasts remained unaffected. CONCLUSIONS TSA inhibits hepatoma cell growth in vitro, which are otherwise particularly resistant to chemotherapy. Its anti-proliferative activity is paralleled by a comparable rate of apoptosis. TSA may be a promising agent for treatment of hepatocellular carcinoma in vivo.

Cocarcinogenic effects of alcohol in hepatocarcinogenesis

Aims: To determine whether an adequate histological diagnosis of gastric polyps can be attained on the basis of forceps biopsy. Patients and methods: In a prospective multicentre study, 194 patients with 222 endoscopically removable gastric polyps (≥5 mm) underwent forceps biopsy and complete polypectomy. Patients with fundic gland polyps and polyposis syndrome were not included. Specimens were evaluated by primary and reference pathologists, and the complication rate of gastric polypectomy was also determined. Results: Of the 222 polyps, histological examination of the polypectomy specimens revealed tumour-like lesions in 77% (10% focal foveolar hyperplasia, 59% hyperplastic polyps, 4% inflammatory fibroid polyps, 4% other polyps) and neoplasia in 19% (10% tubular adenoma, 2% tubulovillous adenoma, 1% high grade intraepithelial neoplasia, 6% adenocarcinoma). When biopsy results were compared, complete agreement was found in 124 cases (55.8%) and, in an additional 77 cases (34.7%), the clinically important differentiation between tumour-like lesions and neoplasia was possible. However, relevant differences were found by the reference pathologist in six cases (2.7%), the most common reason being failure of biopsy to reveal foci of carcinoma in hyperplastic polyps. Bleeding was observed after polypectomy in 16 patients (7.2%), in 15 of whom it was managed conservatively. Conclusions: We recommend complete removal by an experienced endoscopist of all epithelial gastric polyps larger than 5 mm after thorough individualised risk-benefit analysis.

Antigastric autoantibodies in Helicobacter pylori infection: implications of histological and clinical parameters of gastritis

Alcohol is a major aetiological factor in hepatocarcinogenesis but our understanding of its importance as a modulating factor is just beginning to emerge. In the present review, a number of possible cofactors and mechanisms are discussed by which alcohol may enhance the development of hepatoma. These include dietary or environmental carcinogens ingested along with alcoholic beverages, alcoholic cirrhosis as a precancerous condition, and the effects of alcohol metabolism.

Readmissions and adverse drug reactions in internal medicine: the economic impact

Background—It has recently been shown that humoral antigastric autoreactivities occur in a substantial number ofHelicobacter pylori infected patients. Aims—To analyse the relevance of such antigastric autoantibodies for histological and serological parameters of the infection as well as for the clinical course. Methods—Gastric biopsy samples and sera from 126 patients with upper abdominal complaints were investigated for evidence of H pylori infection using histology and serology. Autoantibodies against epitopes in human gastric mucosa were detected by immunohistochemical techniques. Histological and clinical findings of all patients were then correlated with the detection of antigastric autoantibodies. Results—H pylori infection was significantly associated with antigastric autoantibodies reactive with the luminal membrane of the foveolar epithelium and with canalicular structures within parietal cells. The presence of the latter autoantibodies was significantly correlated with the severity of body gastritis, gastric mucosa atrophy, elevated fasting gastrin concentrations, and a decreased ratio of serum pepsinogen I:II. Furthermore the presence of anticanalicular autoantibodies was associated with a greater than twofold reduced prevalence for duodenal ulcer. Conclusion—The data indicate that antigastric autoantibodies play a role in the pathogenesis and outcome of H pylori gastritis, in particular in the development of gastric mucosal atrophy.

Health-related quality of life of patients with multiple organ dysfunction: Individual changes and comparison with normative population

Background.  Recent studies show that nearly half of the hospitalized patients are readmitted within 6 months from discharge. No data exist about the relationship between adverse drug reactions (ADRs) and readmittance to a department of internal medicine.

Pentoxifylline downregulates profibrogenic cytokines and procollagen I expression in rat secondary biliary fibrosis.

ObjectiveTo determine health-related quality of life in medical intensive care patients with multiple organ dysfunction. DesignProspective, observational study. SettingA 12-bed, noncoronary, medical intensive care unit of a university hospital. PatientsBetween June 1998 and May 1999, 318 consecutively admitted adult patients with an intensive care unit stay of >24 hrs were studied. Measurements and Main ResultsHealth-related quality of life was assessed using a generic instrument, the Medical Outcomes Study Short Form-36 Health Survey, at admission and at 6-month follow-up. Patients who developed multiple organ dysfunction (n = 170) consumed 85% of the therapeutic activity provided in the intensive care unit. Compared with age- and sex-adjusted general population controls, multiple organ dysfunction patients had a worse preadmission health-related quality of life than other intensive care unit patients, predominantly due to a higher burden of comorbid disease. In a multivariate analysis, multiple organ dysfunction was the only variable independently associated with deteriorated physical health domains at follow-up (odds ratio, 4.4; 95% confidence interval, 1.3–14.6;p = .015), but it had no impact on dimensions of mental health. Analyzing the impact of different organ system failures, respiratory failure (odds ratio, 4.1; 95% confidence interval, 1.6–10.3;p = .002) and acute renal failure (odds ratio, 3.3; 95% confidence interval, 1.0–11.5;p = .05) increased the risk of deteriorated physical health at follow-up. No impact of the various organ system failures on mental health was noted. At 6-month follow-up, 83–90% of survivors had regained their previous health-related quality of life, and 94% were living at home with their families. ConclusionsThis study has shown that preadmission health-related quality of life of our medical, noncoronary patients was substantially reduced compared with a matched general population. This demonstrates the need to take prehospitalization health-related quality of life into account when examining the outcomes of intensive care unit survivors. Multiple organ dysfunction was the major determinant of poor physical health at follow-up, but it had no impact on mental health domains.