Educational status and differences in left ventricular mass and ejection fraction - The role of BMI and parameters related to the metabolic syndrome: A longitudinal analysis from the population-based CARLA cohort.

BACKGROUND AND AIMS: Higher ventricular mass has been reported in non-white US-Americans with low educational status and in socially isolated people. To assess the impact of education on cardiac mass and function in the general population and to identify mediators. METHODS AND RESULTS: Data from a German population-based sample were used (CARLA cohort, n = 1779 at baseline, n = 1436 at the four-year follow-up). Ventricular mass indexed on height (LVMI) and ejection fraction, using Teichholz's formula (EFTZ), were measured. Education was assessed using the ISCED classification. Mediator analyses were performed using the R-macro 'mediation' to compute the average direct effect and the average causal mediated effect after confounder adjustment. Sensitivity analyses for unobserved confounders were performed. Considered mediators were BMI, waist-to-hip ratio, HbA1c, and systolic and diastolic blood pressures. We found differences in LVMI and EFTZ, both at baseline and follow-up, between educational levels in women (lowest vs highest educational level: 15.6 g, 95% CI: -25.7, -5.6), but not in men. Similarly, women (lowest vs highest educational level at baseline: 3.3%, 95% CI: 0.8-5.7), but not men, of higher educational levels had a higher EFTZ of comparable magnitude at baseline and follow-up. Of the considered mediators, BMI explained 55.9% at baseline and 54.1% at follow-up of the educational effect, while other potential mediators had no significant effect. Relations remained constant between baseline and follow-up. CONCLUSIONS: Women with low educational levels tend to have a higher ventricular mass and lower EF, which can be explained by a higher BMI in this group.

Educational level and chronic inflammation in the elderly--the role of obesity: results from the population-based CARLA study.

This study aimed to assess the mediating role of anthropometric parameters in the relation of education and inflammation in the elderly. Cross-sectional data from the population-based CARdio-vascular Disease, Living and Ageing in Halle study were used after excluding subjects with a plasma level of high-sensitive C-reactive protein (hsCRP) above 10 mg L(-1) (916 men/760 women remaining). Education was categorized in accordance with International Standard Classification of Education. As inflammation parameters, the soluble tumour necrosis factor type 1 (sTNF-R1), hsCRP and interleukin 6 (IL-6) were taken into account. Anthropometric parameters were the body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHeR). We used covariate adjusted mixed models to assess associations. Effect measures were the natural indirect effect (NIE), controlled direct effect and total effect (TE). Education was associated with sTNF-R1, hsCRP and IL-6 in men, and sTNF-R1 and hsCRP in women. Anthropometric parameters correlated with all inflammation parameters after covariate adjustment. BMI and WHeR were strong mediators of educational differences in sTNF-R1 (percentage of NIE of TE: 28% in men; 33% in women) and hsCRP (percentage of NIE of TE: 35% in men; 52% in women), while WHR was the weakest mediator. General obesity mediates roughly one-third of the association of education with chronic inflammation in the elderly.

Inflammation and echocardiographic parameters of ventricular hypertrophy in a cohort with preserved cardiac function.

OBJECTIVE: To investigate the association between inflammation and selective echocardiographic parameters (EP) characteristic for ventricular hypertrophy in cross-sectional and longitudinal population-based analyses. METHODS: Baseline (711 men, 659 women: 45-83 years) and 4-year follow-up data (622 men, 540 women) of the prospective, population-based CARdio-vascular disease, Living and Ageing in Halle (CARLA)study after exclusion of participants with cardiacvascular diseases were analysed. Inflammation parameters: soluble tumour necrosis factor receptor 1 (sTNF-R1), high-sensitivity C reactive protein (hsCRP) and interleukin 6 (IL-6). EPs: left ventricular mass (LVM), left atrial systolic dimension (LADS), interventricular septum diameter (IVSD), posterior wall dimension (PWD), left ventricular diastolic diameter (LVDD), ejection fraction according to Teichholz (EF). For the longitudinal analyses baseline to follow-up differences were considered. Effect sizes were determined by using multiple linear regression and mixed models. Missing values were replaced by means of multiple imputations. RESULTS: Men had higher sTNF-R1 levels; means of hsCRP and IL-6 were similar in men and women. In multiple regression models, sTNF-R1 was associated with LADS (1.4 mm/1000 pg/mL sTNF-R1, 95% CI 0.6 to 2.1) in men. Respecting confounder hsCRP was associated with LVM (5.2 g/10 mg/L hsCRP, 95% CI 1.6 to 8.8), IVSD (0.2 mm/10 mg/L hsCRP, 95% CI 0 to 0.3) and PWD (0.2 mm/10 mg/L hsCRP, 95% CI 0.1 to 0.3) in women, while there were no relevant effects in analysis of IL-6 in both sexes. The baseline to follow-up change in EPs was not relevantly associated with sTNF-R1, hsCRP or IL-6. CONCLUSIONS: STNF-R1, hsCRP and IL-6 were inadequate predictors for structural changes of the heart at follow-up, while weak cross-sectional associations are restricted to certain EPs and depend on sex.

Validation of the German Diabetes Risk Score within a population-based representative cohort.

AIM: To validate the German Diabetes Risk Score within the population-based cohort of the Cardiovascular Disease - Living and Ageing in Halle (CARLA) study. METHODS: The sample included 582 women and 719 men, aged 45-83 years, who did not have diabetes at baseline. The individual risk of every participant was calculated using the German Diabetes Risk Score, which was modified for 4 years of follow-up. Predicted probabilities and observed outcomes were compared using Hosmer-Lemeshow goodness-of-fit tests and receiver-operator characteristic analyses. Changes in prediction power were investigated by expanding the German Diabetes Risk Score to include metabolic variables and by subgroup analyses. RESULTS: We found 58 cases of incident diabetes. The median 4-year probability of developing diabetes based on the German Diabetes Risk Score was 6.5%. The observed and predicted probabilities of developing diabetes were similar, although estimation was imprecise owing to the small number of cases, and the Hosmer-Lemeshow test returned a poor correlation (chi-squared = 55.3; P = 5.8*10⁻¹²). The area under the receiver-operator characteristic curve (AUC) was 0.70 (95% CI 0.64-0.77), and after excluding participants ≥66 years old, the AUC increased to 0.77 (95% CI 0.70-0.84). Consideration of glycaemic diagnostic variables, in addition to self-reported diabetes, reduced the AUC to 0.65 (95% CI 0.58-0.71). A new model that included the German Diabetes Risk Score and blood glucose concentration (AUC 0.81; 95% CI 0.76-0.86) or HbA(1c) concentration (AUC 0.84; 95% CI 0.80-0.91) was found to peform better. CONCLUSIONS: Application of the German Diabetes Risk Score in the CARLA cohort did not reproduce the findings in the European Prospective Investigation into Cancer and Nutrition (EPIC) Potsdam study, which may be explained by cohort differences and model overfit in the latter; however, a high score does provide an indication of increased risk of diabetes.

Acute myocardial infarction and cardiogenic shock: prognostic impact of cytokines: INF-γ, TNF-α, MIP-1ß, G-CSF, and MCP-1ß.

BACKGROUND: The IABP SHOCK trial was designed as a morbidity-based randomized controlled trial to determine the effect of intraaortic balloon pulsation (IABP) in patients with infarct-related cardiogenic shock (CS). The primary endpoint was the change in the APACHE II score over a 4-day period. The prospective hypothesis was that adding IABP therapy to "standard care" would reduce CS-triggered multiorgan dysfunction syndrome (MODS). The primary endpoint showed no difference between conventionally managed cardiogenic shock patients and those with additional IABP support. In an inflammatory marker substudy, we analyzed the prognostic value of the cytokines interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-1ß (MIP-1ß), granulocyte-colony stimulating factor (G-CSF), and monocyte chemoattractant protein-1ß (MCP-1ß). We also investigated the influence of IABP support, age, and gender on cytokine levels. DESIGN: The inflammatory marker substudy of the prospective, randomized, controlled, open label IABP SHOCK Trial (ClinicalTrials.gov ID NCT00469248). MATERIALS AND METHODS: A prospective, randomized, single-center study in a 12-bed intensive care unit at a university hospital was performed. A total of 40 consecutive patients were enrolled. The observational period was 96 h. RESULTS: The investigated cytokines showed a significant contribution in the prediction of mortality. Initial (on admission) and maximal cytokine levels during the observational period showed a similar predictive power. Patients with elevated levels of pro- and antiinflammatory cytokines had a higher risk of dying. The maximal level measured over the observation period in the hospital was also suited to identify the survivors. Close correlations between maximal cytokine levels resulted in the choice of only one independent marker (MIP-1ß) into the multivariate model (OR 1.024, 95% CI 1.005-1.043). Initial cytokine levels were also suitable to predict the survivors; the risk of death significantly increases with increasing IFN-γ level (OR 1.119, 95% CI 1.005-1.246). Cytokine levels were not affected by the presence of IABP support. Age (< 75 or > 75 years) and gender did not have a clinically relevant effect on INF-γ, TNF-α, MIP-1ß, G-CSF, and MCP-1 in CS patients. CONCLUSION: The inflammatory response in patients with myocardial infarction complicated by CS, as reflected by the inflammatory markers INF-γ, TNF-α, MIP-1ß, G-CSF, and MCP-1ß, have been shown to be of prognostic value in estimating clinical outcome.

[A cohort study investigating risk factors for cardiovascular disease in an urban elderly East-German population (CARLA study)]. / Kohortenstudie zu Risikofaktoren für Herz-Kreislauf-Krankheiten in einer urbanen älteren ostdeutschen Allgemeinbevölkerung (CARLA-Studie).

The CARLA study (Cardiovascular Disease, Living and Ageing in Halle) is a population-based cohort study of the elderly general population of the city of Halle (Saale) aged 45-83 years. The aim is to investigate established cardiovascular risk factors and a reduced heart rate variability (HRV) as indicator of autonomous dysfunction. In total, 1779 probands (812 women and 967 men) were investigated at baseline. Of those, 1436 participants were re-examined at a 4-years follow-up. The corresponding response rates were 64.1% in the baseline and 92% in the follow-up investigation. In the cross-sectional analysis a clear decrease was found in all parameters of HRV with increasing age, but no consistent associations to cardiovascular classical risk factors and diseases could be shown. Compared to other German cohorts a striking risk constellation was found consisting of high prevalence of hypertension, frequent occurrence of central overweight (measured by waist-hip ratio) and high prevalence of diabetes mellitus. These findings will be further scrutinized in the ongoing analyses of the 4-year follow-up and the 10-years follow-up which will start in 2012.

["Without any practical relevance?": 3 years of student evaluation of an interdisciplinary curriculum for prevention and health promotion in undergraduate medical education]. / "Ohne jede Relevanz für die Praxis?": Studentische Evaluation des Querschnittsfaches Prävention und Gesundheitsförderung im Medizinstudium über 3 Jahre.

BACKGROUND: The topic "prevention and health promotion" (Q10) was introduced into the medical training in Germany by the new medical licensing regulations in 2004. For the conception of an effective curriculum in the context of quality assurance, a continuous evaluation by the target group is necessary. Of importance are particularly the subjective success in learning and its interdependence to invested time, achievement expenditure and perceived relevance of the topics. METHODS: Medical students (N=660) of the fifth academic years of 2007-2009 at the Martin-Luther-University Halle-Wittenberg were asked about their opinion after completing their Q10 curriculums by means of a standardised questionnaires. Emphasis of the questioning was placed on self estimates about success in learning, expenditure of time, evaluation of instruction elements, perceived relevance of prevention topics and the motivation for further occupation with the topic field. The collection instruments covered multiple choice questions, decimal number data and 5-point Likert scales. RESULTS: 510 questionnaires (77% return) could be evaluated. The curriculum "prevention and health promotion" was continuously evaluated over 3 years with increasingly indicated performance requirements and expenditure of time regarding instruction elements and success in learning. The invested time in lecture visits correlated positively with relevance-attribution (r=0.16, p<0.01) and subjective success in learning (r=0.29, p<0.001). The strongest correlations regarding subjective success in learning were shown in the evaluation of the instruction elements (r=0.65, p<0.001), perceived relevance of the topic (r=0.42, p<0.001) and motivation (r=0.45, p<0.001). CONCLUSIONS: Self-estimated success in learning within the interdisciplinary field of prevention and health promotion can be fostered by elucidating the relevance of the topic. Increasing requirements and expenditure of time for the preparation of performance records seem to be a less effective stimulus for successes in learning as the promotion of the lecture visit. The selection of suitable teaching and testing formats for prevention and health should orient itself - apart from objective success measurement - also on student evaluations.

[Prognostic Relevance of the Metastatic Localisation in Patients with Stage IV NSCLC - Results of a Prospective Epidemiological Study]. / Prognostische Relevanz der Metastasenlokalisation bei nicht kleinzelligem Bronchialkarzinom im Tumorstadium IV - Ergebnisse einer prospektiven epidemiologischen Studie.

Patients with non-small cell lung cancer (NSCLC) frequently suffer from stage IV disease at the time of presentation. Survival of these patients is disadvantageous although they may benefit from chemotherapy. The main purpose of this investigation was to evaluate the prognostic relevance of the metastatic localisation in unselected patients. The second purpose was to evaluate the impact of clinical characteristics on the kind of decision-making in patients with stage IV NSCLC in an epidemiological manner.[nl]Clinical data as well as survival of 336 patients with stage IV NSCLC were analysed. The recruitment period was 3? years, mean follow-up was 24 months. This investigation was part of the HALLUCA studies which were sponsored by the German Ministry of Health.[nl]Localisation-dependent median and 1-year survivals were significantly different and varied between 2.2 months and 4.7 % (liver metastases) and 11.0 months and 44.5 % (lung metastases). The different survival remained significant in the multivariate analyses with age, performance status, treatment and histology as co variables. The chemotherapy rate of all patients with stage IV NSCLC was 39 %. Patients with liver, bone and multiple metastases received less often chemotherapy compared to patients with other metastases although the performance status was not different to the other groups.[nl]Although there are some limitations in this investigation, these epidemiological data demonstrate the prognostic heterogeneity of stage IV NSCLC patients which should be considered for stratification in controlled clinical trials. Regional treatment decision-making is different from guidelines and controlled clinical trials. Further regionally orientated trials are necessary to improve the transformation from clinical trials to regional medical care.

Course of Crohn's disease prior to establishment of the diagnosis.

BACKGROUND: The course of Crohn's disease prior to the establishment of the diagnosis is widely unknown. Therefore, we instigated a survey amongst newly diagnosed patients. PATIENTS AND METHODS: Patients diagnosed with CD less than 12 months before enrollment were included. Data on demography, social status, time interval to diagnosis, symptoms, and health care service use were collected in a retrospective, web-based, census. Patients were contacted in cooperation with two organizations: a German patients' organization (Deutsche Morbus Crohn/Colitis ulcerosa Vereinigung e.V. [DCCV]) and a professional organization of German gastroenterologists (Berufsverband der Niedergelassenen Gastroenterologen Deutschlands e.V. [bng]). Study participation was anonymous by use of a transaction number. RESULTS: The median interval period between onset of first symptoms and diagnosis was 13 months. During this time, participants reported having five doctor consultations on average, with 44% of them having a mean of 1.5 hospitalizations. 65% were unfit for work with a 14 day median (2 to 480 days) due to their symptoms. A mean (+/-SD) of 8.6 (+/-7.1) diagnostic tests were performed before the diagnosis was established. Overall health state was judged as temporarily bad or very bad by 84% of the participants. Age at diagnosis, characteristic symptoms, and localization of the disease for the participants did not differ from previously reported international data. DISCUSSION: This web-based survey shows a substantial time interval of over one year until diagnosis of Crohn's disease amongst the study participants. This period is characterized by both psychological stress and impaired ability to work.

Concomitant traumas influence prognosis in melanomas of the nail apparatus.

BACKGROUND: In nail apparatus melanomas (NAM), the role of standard melanoma prognostic factors is under discussion. The prognostic influence of traumas to the clinically apparent tumour has not been sufficiently examined. OBJECTIVES: To estimate the influence of traumas against the background of standard prognostic factors on the course of NAM. METHODS: In 33 patients (20 women, 13 men, median age 65.0 years) with NAM (median tumour thickness 3.5 mm), we retrospectively examined a detailed history of trauma to the affected extremity at first presentation. Histological or other standard prognostic factors and follow-up were studied prospectively using a standardized protocol. RESULTS: Of 33 patients, 21 had suffered injury to the clinically apparent melanoma primary between 4 and 72 months prior to definitive surgical treatment (diagnostic biopsy up to 3 months ahead of excision of the melanoma was not considered). Eight of these patients had undergone inadequate therapy procedures. In Kaplan-Meier analysis, trauma to the clinically apparent tumour and tumour thickness were found to be significant prognostic factors for recurrence-free survival, and trauma to the clinically apparent tumour, Clark level and tumour thickness were significant prognosis predictors for overall survival. In Cox's proportional hazards model, trauma to the clinically apparent tumour was found to be a significant and independent risk factor with regard to overall survival (hazard ratio 5.39; P = 0.029). An influence of trauma on the primary pathogenesis of NAM could not be confirmed. Only three patients reported trauma prior to the onset of tumour. CONCLUSIONS: From our data, trauma to the clinically apparent tumour might be a considerable risk factor in NAM. The diagnosis of NAM should be considered in lesions of the nail apparatus and further deterioration of the prognosis due to inadequate therapeutic attempts or injury to the NAM should be avoided.

Chemotherapy for advanced gastric cancer.

BACKGROUND: Gastric cancer currently ranks second in global cancer mortality. Most patients are either diagnosed at an advanced stage, or develop a relapse after apparently curative operation. Apart from supportive measures, systemic chemotherapy is the only treatment option available in this situation. OBJECTIVES: To assess the effect of chemotherapy versus best supportive care, combination versus single agent chemotherapy and different combination chemotherapy regimens in advanced gastric cancer. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE and EMBASE up to February 2004 and reference lists of articles. We also contacted pharmaceutical companies as well as national and international experts. SELECTION CRITERIA: Randomised controlled trials on systemic intravenous chemotherapy versus best supportive care, combination versus single agent chemotherapy and different combination chemotherapies in advanced gastric cancer. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. A third investigator was consulted in case of disagreements. We contacted study authors to obtain missing information. MAIN RESULTS: Chemotherapy versus best supportive care consistently demonstrated a significant benefit in terms of overall survival in favour of the group receiving chemotherapy (Hazard Ratios (HR) 0.39; 95% confidence intervals (CI) 0.28 to 0.52). Combination versus single-agent chemotherapy provides evidence for a survival benefit in favour of combination chemotherapy (HR 0.85; 95% CI 0.76 to 0.96). Numbers included in these comparisons were 184 and 1338 participants respectively. This benefit is achieved at the price of increased toxicity in the combination chemotherapy arms. When comparing 5-FU/cisplatin-containing combination therapy regimens with anthracyclines versus those without anthracyclines (HR 0.77; 95% CI 0.62 to 0.95 based on 501 participants) and 5-FU/anthracycline-containing combinations with cisplatin versus those without cisplatin (HR 0.83; 95% CI 0.76 to 0.91 based on 1147 participants), there was a significant survival benefit for regimens including 5-FU, anthracyclines and cisplatin. AUTHORS' CONCLUSIONS: Chemotherapy significantly improves survival in comparison to best supportive care. In addition, combination chemotherapy improves survival compared to single-agent 5-FU, but the effect size is much smaller. Among the combination chemotherapy regimens studied, best survival results are achieved with regimens containing 5-FU, anthracyclines and cisplatin. In this category, ECF (epirubicin, cisplatin and continuous infusion 5-FU) is tolerated best.

High-dose therapy for patients with primary multifocal and early relapsed Ewing's tumors: results of two consecutive regimens assessing the role of total-body irradiation.

PURPOSE: Risk stratification of metastatic and relapsed Ewing's tumors (ETs) has been a matter of debate during the last decade. Patients with bone or bone marrow metastases or early or multiple relapses constitute the worst risk group in ET and have a poorer prognosis than patients with primary lung metastases or late relapses. In this article, the results of the present Meta European Intergroup Cooperative Ewing Sarcoma Study (MetaEICESS) (tandem melphalan/etoposide [TandemME]) were compared with the result of the previous study (hyper melphalan/etoposide [HyperME]), both at 5 years, in a patient population within the same high-risk stratum to determine toxicity. PATIENTS AND METHODS: Among 54 eligible patients, 26 were treated according to the HyperME protocol, and 28 were treated according to TandemME protocol. Patients received six cycles of the Cooperative Ewing Sarcoma Study treatment in HyperME and six cycles of the EICESS treatment in TandemME as induction chemotherapy. Patients also received involved-compartment irradiation for local intensification and myeloablative systemic intensification consolidation with hyperfractionated total-body irradiation (TBI) combined with melphalan/etoposide in HyperME or two times the melphalan/etoposide in TandemME followed by autologous stem-cell transplantation. RESULTS: The event-free survival (EFS) rate +/- SD in HyperME and TandemME was 22% +/- 8% and 29% +/- 9%, respectively. The dead of complication rate was 23% in HyperME and 4% in TandemME. CONCLUSION: TandemME offers a decent, albeit still not satisfactory, rate of long-term remissions in most advanced ETs (AETs), with short-term treatment and acceptable toxicity. TBI was not required to maintain EFS level in this setting but was associated with a high rate of toxic death. Future prospective studies in unselected patients are warranted to evaluate high-dose therapy in an unselected group of patients with AET.

Effects of short-term treatment with diclofenac-colestyramine on renal function and urinary prostanoid excretion in patients with type-2 diabetes.

OBJECTIVE: To determine the effect of short-term administration of diclofenac-colestyramine on glomerular filtration rate (GFR), renal plasma flow (RPF) and urinary excretion of prostanoids in patients with type-2 diabetes without and with impaired renal function. METHODS: In the randomised, single-blind, placebo-controlled, two-period crossover study, 32 patients with type-2 diabetes (group 1: 16 patients without impaired renal function, creatinine clearance > or =80 ml/min and group 2: 16 patients with impaired renal function, creatinine clearance 30-79 ml/min) received 140 mg diclofenac-colestyramine (corresponding to 75 mg diclofenac sodium) or placebo twice a day on days 1 and 2 and once on day 3 with a wash-out period of 6 days between the two periods. GFR was assessed using both measurement of creatinine clearance and calculation of inulin clearance and RPF was assessed using calculation of para-aminohippurate (PAH) clearance after the short-term administration on day 3. Urinary excretion of prostanoids (PGE(2), PGE-M, 6-keto-PGF(1alpha), 2,3-dinor-6-keto-PGF(1alpha), TxB(2), 2,3-dinor-TxB(2) and 11-dehydro-TxB(2)) were measured before and after drug intake. RESULTS: Comparison with placebo showed no effect of diclofenac-colestyramine on creatinine, inulin or PAH clearance ( P>0.05) in patients with type-2 diabetes either without or with impaired renal function. The differences in creatinine, inulin and PAH clearance between the two groups of patients were not influenced by diclofenac-colestyramine. Urinary excretion of PGE(2), PGE-M, 6-keto-PGF(1alpha), 2,3-dinor-6-keto-PGF(1alpha), TxB(2), 2,3-dinor-TxB(2) ( P=1.89) and 11-dehydro-TxB(2) was significantly reduced by diclofenac-colestyramine. CONCLUSION: These results indicate that proven non-specific cyclooxygenase inhibition by short-term administration of diclofenac-colestyramine did not affect renal haemodynamic function (GFR, RPF) in patients with type-2 diabetes either without or with impaired renal function.

Study of Health In Pomerania (SHIP): a health examination survey in an east German region: objectives and design.

OBJECTIVES: The reason for the Study of Health in Pomerania (SHIP) is the lack of epidemiological studies with a broad range of health indicators. Furthermore, in Germany there is a need for studies that take into account the particular situation of life after the reunification. One objective of SHIP is to provide prevalence estimates on a broad range of diseases, risk and health factors for a defined region in the former GDR. METHODS: A sample of 7008 women and men aged 20 to 79 years in a north-east region of Germany, 4900 expected participants. The sample was drawn in two steps: First, 32 communities in the region were selected. Second, within the communities a simple random sample was drawn from residence registries, stratified by gender and age. The data collection and instruments include four parts: oral health examination, medical examination, health-related interview, and a health- and risk-factor-related questionnaire. The oral health examination includes the teeth, periodontium, oral mucosa, craniomandibular system, and prosthodontics. The medical examination includes blood pressure measurements, electrocardiography, echocardiography, carotid, thyroid and liver ultrasounds, neurological screening, blood and urine sampling. The computer-aided health-related interview includes cardiovascular symptoms, utilisation of medical services, health-related behaviours, and socioeconomic variables. The self-administered questionnaire comprises housing conditions, social network, work conditions, subjective well-being and individual consequences from the German reunification.

Screening for high-grade cervical intra-epithelial neoplasia and cancer by testing for high-risk HPV, routine cytology or colposcopy.

The validity of testing for high-risk types of human papillomavirus (HPV) in cervical cancer prevention programs is undetermined. We compared the performance on primary screening of HPV DNA testing, cytology and colposcopy in detecting cervical intra-epithelial neoplasia (CIN) grade 2 or 3 or cancer. A cohort of 4,761 women, median age 35 years, was screened by routine cytology, routine colposcopy and testing for high-risk HPV by a PCR-based method. Within an 8-month period, women with abnormal findings on cytology or screening colposcopy or in whom high-risk HPV types were detected were referred for colposcopy and biopsy. Women negative on all initial screening tests were followed by a second screening examination. To correct for work-up bias, the true prevalence of CIN 2 or 3 or cancer was estimated by projection from histologically verified subgroups. Cervical biopsies were taken in 364 women (7.6%), of whom 114 (2.4%) showed CIN 2 (n = 34) or CIN 3 (n = 71) or cancer (n = 9). High-risk HPV testing achieved bias-corrected performance measures of 89.4% sensitivity, 93.9% specificity, 35.8% positive predictive value and 99.6% negative predictive value. Bias-corrected rates of true- and false-positives by high-risk HPV testing compared to cytology (colposcopy) were about 4.5 (6.7) and 19.1 (7.4) times higher, respectively. The quality of routine cytology was controlled by computer-assisted review, and the observed number of true-positives more than doubled after adding automated review results. In middle-aged women, testing for high-risk HPV types, particularly when negative, may be used to increase the screening interval in programs for secondary prevention of cervical cancer.

Occupational risk factors for renal cell carcinoma: agent-specific results from a case-control study in Germany. MURC Study Group. Multicenter urothelial and renal cancer study.

BACKGROUND: This case-control study was conducted to estimate the renal cell cancer (RCC) risk for exposure to occupation-related agents, besides other suspected risk factors. METHODS: In a population-based multicentre study, 935 incident RCC cases and 4298 controls matched for region, sex, and age were interviewed between 1991 and 1995 for their occupational history and lifestyle habits. Agent-specific exposure was expert-rated with two job-exposure matrices and a job task-exposure matrix. Conditional logistic regression was used to calculate smoking adjusted odds ratios (OR). RESULTS: Very long exposures in the chemical, rubber, and printing industries were associated with risk for RCC. Males considered as 'substantially exposed to organic solvents' showed a significant excess risk (OR = 1.6, 95% CI : 1.1-2.3). In females substantial exposure to solvents was also a significant risk factor (OR = 2.1, 95% CI : 1.0-4.4). Excess risks were shown for high exposure to cadmium (OR = 1.4, 95% CI : 1.1-1.8, in men, OR = 2.5, 95% CI : 1.2-5.3 in women), for substantial exposure to lead (OR = 1.5, 95% CI : 1.0-2.3, in men, OR = 2.6, 95% CI : 1.2-5.5, in women) and to solder fumes (OR = 1.5, 95% CI : 1.0-2.4, in men). In females, an excess risk for the task 'soldering, welding, milling' was found (OR = 3.0, 95% CI : 1.1-7.8). Exposure to paints, mineral oils, cutting fluids, benzene, polycyclic aromatic hydrocarbons, and asbestos showed an association with RCC development. CONCLUSIONS: Our results indicate that substantial exposure to metals and solvents may be nephrocarcinogenic. There is evidence for a gender-specific susceptibility of the kidneys.

Occupational risk factors for urothelial carcinoma: agent-specific results from a case-control study in Germany. MURC Study Group. Multicenter Urothelial and Renal Cancer.

BACKGROUND: This multicentre population-based case-control study was conducted to estimate the urothelial cancer risk for occupational exposure to aromatic amines, polycyclic aromatic hydrocarbons (PAH), and chlorinated hydrocarbons besides other suspected risk factors. METHODS: In a population-based multicentre study, 1035 incident urothelial cancer cases and 4298 controls matched for region, sex, and age were interviewed between 1991 and 1995 for their occupational history and lifestyle habits. Exposure to the agents under study was self-assessed as well as expert-rated with two job-exposure matrices and a job task-exposure matrix. Conditional logistic regression was used to calculate smoking adjusted odds ratios (OR) and to control for study centre and age. RESULTS: Urothelial cancer risk following exposure to aromatic amines was only slightly elevated. Among males, substantial exposures to PAH as well as to chlorinated solvents and their corresponding occupational settings were associated with significantly elevated risks after adjustment for smoking (PAH exposure, assessed with a job-exposure matrix: OR = 1.6, 95% CI: 1.1-2.3, exposure to chlorinated solvents, assessed with a job task-exposure matrix: OR = 1.8, 95% CI: 1.2-2.6). Metal degreasing showed an elevated urothelial cancer risk among males (OR = 2.3, 95% CI: 1.4-3.8). In females also, exposure to chlorinated solvents indicated a urothelial cancer risk. Because of small numbers the risk evaluation for females should be treated with caution. CONCLUSIONS: Occupational exposure to aromatic amines could not be shown to be as strong a risk factor for urothelial carcinomas as in the past. A possible explanation for this finding is the reduction in exposure over the last 50 years. Our results strengthen the evidence that PAH may have a carcinogenic potential for the urothelium. Furthermore, our results indicate a urothelial cancer risk for the use of chlorinated solvents.

Differential expression of heat shock proteins 70-1 and 70-2 mRNA after ischemia-reperfusion injury of rat kidney.

Ischemia-reperfusion injury in the kidney is known to cause induction of the inducible form of the 70 kDa heat shock protein HSP70i (or HSP72). However, knowledge of the expressional regulation of the two coding genes for HSP70i - HSP70-1 gene and HSP70-2 gene - is very limited. We investigated the time course of HSP70-1 and -2 mRNA expression and its relation to cellular ATP levels in the renal cortex after different periods of unilateral warm renal ischemia (10-60 min) and reperfusion (up to 60 min) in 10-week-old male Wistar rats. Immediately after ischemia there was a significant induction of both HSP70i genes. While HSP70-1 expression constantly increased (up to 4-fold) during reperfusion, even to a higher extent with prolongation of ischemia, HSP70-2 mRNA - which was generally expressed at a far lower level than HSP70-1 mRNA - was strongly induced (3-fold) during reperfusion only after brief periods (10 min) of ischemia. Cellular ATP levels rapidly dropped to 5% with ischemia and the pattern of recovery during reperfusion significantly depended on the duration of the ischemic period, thus showing a good relation with the heat shock (protein) gene expression. We conclude that HSP70-2 is the more sensitive gene with a lower activation threshold by mild injury, while the HSP70-1 gene mediates the major response of heat shock protein induction after severe injury.

Impact of CYP2E1 genotype in renal cell and urothelial cancer patients.

Genetic polymorphisms of enzymes involved in carcinogen metabolism have been found to influence susceptibility to cancer. Ethanol-inducible CYP2E1 is an enzyme of major toxicological interest because it metabolizes several drugs, precarcinogens and solvents to reactive metabolites. In the present study, we investigated the cytochrome P450 2E1 genetic polymorphism in renal cell/urothelial cancer patients from two German regions, Jena and Halle, different with respect to their environmental pollution degree in comparison with healthy controls from the same regions. DNA of peripheral white blood cells was isolated both from 224 renal cell/urothelial cancer patients and 304 controls. We focussed on polymorphisms in the promoter region and intron 6 of the CYP2E1 gene. The polymorphisms were identified as RFLP's by amplification of the appropriate DNA fragment and subsequent digestion with the restriction enzymes PstI, RsaI and DraI. In Jena as well as in Halle, the frequency distributions of the PstI/RsaI, DraI and combined DraI + PstI/RsaI genotypes showed no significant differences between controls and renal cell/urothelial cancer patients. We did not find significant differences between Jena and Halle. 86.2% of all subjects with a homozygote PstI/RsaI genotype also carried a heterozygote DraI genotype, whereas 5.1% of the subjects with a heterozygote PstI/RsaI genotype also carried a heterozygote DraI genotype. Renal cell cancer as well as urothelial cancer risk was not elevated in patients with heterozygote DraI, PstI/RsaI and combined DraI + PstI/RsaI genotypes (odds ratios slightly insignificantly increased). Interestingly enough, an association between these polymorphisms and renal cell cancer risk was found in the female subgroup but not in the male subgroup. The basis of these sex-specifically increased risks are different frequencies concerning heterozygote and homozygote genotypes in controls and cancer patients. In controls, the heterozygote genotype frequency was lower in females than in males. In renal cell cancer patients, the results were quite the contrary. Summing up, our results demonstrate an lack between CYP2E1 genetic polymorphism and renal cell/urothelial cancer risk.