[Risk factors for urothelial carcinoma: drinking measures, smoking and other life style-related risk factors--results of the Berlin Urothelial Study (BUS)]. / Risikofaktoren für das Urothelkarzinom: Trinkmenge, Rauchen und andere lebensstilbezogene Risikofaktoren--Ergebnisse der Berliner Urothelstudie (BUS).

With the exception of smoking and several occupational exposures there is little knowledge about risk factors for urothelial cancer. A case control study in the area of former West Berlin was performed from 1990-1995 to investigate the role of several lifestyle risk factors, such as smoking, drinking behaviour and regular intake of analgesics and laxatives. The study includes 647 hospital-based incident cases with bladder cancer (n = 571), renal pelvis cancer (n = 51), and ureter cancer (n = 25), and 647 population-based controls which were matched individually by sex and age. Data analyses were carried out using standard methods for case control studies (conditional multiple logistic regression analysis). Odds ratios (OR) and 95% confidence intervals (CI) were applied as effect parameter. Statistically significantly increased odds ratios were observed for current smoking (OR: 3.46, 95% CI: 2.50-4.78), previous but now abandoned smoking (OR: 1.51, 95% CI: 1.09-2.81), and for regular intake of laxatives (OR: 2.52, 95% CI: 1.56-4.09). Furthermore, an increased risk for urothelial cancer was observed for daily consumption of three and more litres of cold drinks (OR: 2.65 95% CI: 1.12-6.24). The results underline that lifestyle factors other than smoking may contribute to a higher risk of urothelial cancer.

Outcome of patients with ventricular assist devices and acute renal failure requiring renal replacement therapy.

The significance of acute renal failure (ARF) for patients treated with a ventricular assist device (VAD) is uncertain. There is little information on the outcome of patients who require renal replacement therapy during treatment with a VAD. A retrospective review was undertaken to evaluate the impact of renal failure requiring renal replacement therapy on such patients. Studied were 227 patients who were supplied with a VAD at the German Heart Institute Berlin. Fifty-five patients required renal replacement therapy during treatment with a VAD. These were compared with patients not needing renal replacement therapy (ARF and non-ARF groups). Significant differences for the end points of survival, heart transplantation, and discharge from hospital were observed in patients with ARF (p < 0.01). Survival was then analyzed according to indications for treatment with a VAD (bridge to transplantation or cardiac recovery after cardiotomy, transplantation, myocardial infarction, myocarditis, and endocarditis). Survival for bridge-to-transplantation patients was clearly influenced in a negative way by ARF (p < 0.01). For cardiac recovery patients, only a small difference in survival was observed (p = 0.05). We conclude that ARF is a negative predictor for bridge-to-transplantation patients. For cardiac recovery patients the impact of ARF on survival is marginally significant.

Urothelial cancer at different tumour sites: role of smoking and habitual intake of analgesics and laxatives. Results of the Berlin Urothelial Cancer Study.

BACKGROUND: In Germany about 20000 new cases of urothelial cancer (UC) and about 7500 deaths from bladder cancer alone occur each year. Among the manifold risk factors, little research has been done on the role of smoking and the habitual intake of analgesics and laxatives-practices that are common in parts of the German population. The aim of this study is to define the proportion of risk derived from these preventable habits for the development of UC at its different sites. Subjects and methods. A case-control study in the area of the former West Berlin was performed from 1990 to 1995 including all newly diagnosed incident cases of UC from the eight hospitals of the study area. Study subjects and population-based controls individually matched by age (+/-2 years) and sex were evaluated by a standardized face-to-face interview about the lifelong exposure to cigarette smoking, analgesics, and laxatives. Adjusted risk analysis was carried out for the main exposure variables in relation to the different sites of UC in the bladder, ureter, and renal pelvis. RESULTS: Six hundred and forty-seven cases of UC (571 bladder, 25 ureter, and 51 renal pelvis) and an identical number of controls were included in the analysis (response rate in cases, 84.6%; in controls, 70.2%). Smoking increased the risk of bladder cancer (BC) by an odds ratio (OR) of 3.22 (95% confidence interval (CI) 2.29-4.52), that of ureter (URC) or renal pelvis cancer (RPC) together by OR 6.20 (95% CI 2.04-18.81), and that of RPC alone by OR 5.91 (95% CI 1.47-23.66). Ex-smoking was associated with an increased risk for BC (OR 1.55, 95% CI 1.10-2.19). Intake of more than 1 kg of phenacetin in analgesic mixtures was associated with an OR of 5.28 for RPC (intake of > or = 1 kg paracetamol, OR 3.27; > or = 1 kg pyrazolones, 1.12) and 0.75 for BC (not significant). Laxatives significantly increased the risk of BC (OR 2.14, 95% CI 1.26-3.63) and RPC/URC (OR 9.62, 95% CI 1. 01-91.24) in both sexes. CONCLUSION: Habitual risks from smoking and intake of laxatives significantly contribute to the development of UC, especially of the renal pelvis and ureter cancer. Intake of at least 1 kg of analgesic substances (anilides, pyrazolones) as calculated from this study base is associated with increased but not significant risks for RPC. These data underline that restrictive and educational measurements focusing on common habits would have a strong impact on preventing UC in Germany.

[Analgesics and laxatives as risk factors for cancer in the efferent urinary tract--results of the Berlin Urothelial Carcinoma Study]. / Analgetika und Laxantien als Risikofaktoren für Krebs der ableitenden Harnwege--Ergebnisse der Berliner Urothelkarzinom-Studie (BUS).

A retrospective case-control study (1990-1995), the Berlin Urothelial Cancer Study (BUS), examined analgesics and laxatives as risks for the induction of urothelial cancer in renal pelvis, ureter and bladder. Especially for renal pelvis cancer could observe substance and dose specific risk of compound analgesics. The analgesic substances Phenacetin, Paracetamol, Acetylsalicylic acid (ASA) and Pyrazolones were assessed. Besides a risk of contact laxatives (chemical or anthranoide ingredients) for urothelial cancer was found, not yet described. The highest risk shows the anthranoide plant Senna. Thus this study confirms the risk of specific analgesic ingredients and found an evidence for a new risk of contact laxatives. As both, analgesics and contact laxatives, are typical OTC--("Over the counter") products, a severe controlling is demanded and for laxatives further studies are needed.

Future evolution of the ESRD patient population--a perspective for the year 2000.

Renal replacement therapy of the next decade in Europe will be strongly influenced by certain epidemiological developments, which can be observed in some parts of the world since several years. The overall incidence rates of new patients will rise up to 300 pmp per year, the prevalence rates of patients on treatment will exceed 1000 pmp in some European countries as well as in Japan and in the USA. This is due to a more than proportional increase in the acceptance rates for people older than 65, mostly patients with type II diabetes and hypertensive nephropathy. In Europe, the proportion of patients with NIDDM and diabetic nephropathy shows marked regional differences, which may be more or less important for the development of the whole patient population. Since diabetes as well as hypertensive disease are conditions with high risks for non-renal complications, one cannot expect important improvements in patient survival in spite of technical developments in dialysis therapy.

[Chronic use of analgesics]. / Daten zum chronischen Schmerzmittelgebrauch.

Quantitative aspects of longterm analgesic intake are presented, based on a case-control-study on the relation between regular analgesic intake and endstage renal failure in the area of West Berlin (1984-86). Lifetime analgesic consumption of more than 1000 persons were investigated. A total of 285 longterm analgesic users (185 cases = 35.8%; 100 controls = 19.3%) were detected. An odd ratio of 2.44 (95% CI: 1.77-3.39) was computed. Regular analgesic intake was defined as an intake of at least 15 analgesic doses per month continuously over a period of at least 12 months. 90% of the regular users preferred mixed analgesics compounds, in most cases with the psychotropic additive caffeine.

[Oncogenic hypophosphatemic osteomalacia]. / Onkogene hypophosphatätmische Osteomalazie.

In the courses of six years a severe hypophosphataemic osteomalacia, painful motor impairment and multiple rib fractures developed in a 51-year-old man. The symptoms gradually improved within one year under treatment with 3 micrograms daily of 1,25-dihydroxycholecalciferol, 3 g phosphorus and 3 g calcium, and biochemical parameters and the bone scintigram became normal. Ultimately, computed tomography, scintigraphy and digital subtraction angiography revealed a highly vascularized tumour in the condylar aspect of the right femur, and it was chiselled out. Histologically it was a mesenchymal phosphaturic tumour of haemangiopericytoma type of questionable benignity. After the operation the patient was symptom-free for some weeks without any drug treatment, but the latter was then resumed because of renewed bone pain. By now, two years later, he is essentially without pain and has full mobility. However, repeat scintigraphy and angiography revealed renewed tumour growth in the right femoral condyle.

Regular analgesic intake and the risk of end-stage renal failure.

The strength of the association between regular analgesic intake (RAI) and end-stage renal failure (EF) has been insufficiently established until now. A case-control study was conducted to estimate the relative risks (RR) of EF after RAI (defined as consumption of 15 or more analgesic doses per month for a continuous period of at least 1 year) for cumulative drug intake, single-ingredient analgesics, combinations, and specific compounds. The case group included all patients with EF undergoing renal replacement therapy in the area of West Berlin (1984-1986, n = 921). Control subjects, matched to cases by sex, age, and nationality, were selected from a group of patients in outpatient clinics. Matching was possible for 517 cases. The RR of EF after RAI of any analgesic was 2.44 (95% confidence interval: 1.77-3.39) and after RAI of combination drugs 2.65 (95% confidence interval 1.91-3.67). No significant increase was found, however, after RAI of single-ingredient analgesics. The RR after RAI of combination drugs and for the most preferred analgesic ingredients (phenacetin, paracetamol, acetylsalicylic acid, phenazones, caffeine) increased with dose. Furthermore, a dose-time-related RR after RAI of the longest used preparation was found. Thus, the results clearly show an increased RR of EF after RAI related to both dose and exposure time of mixed analgesic compounds, but not for the use of only single-ingredient analgesics.

Effect of dialyzer membranes on in vitro generation of eicosanoids.

Eicosanoids are potent substances released from blood cells after contact with foreign materials. Eicosanoid generation, in addition to complement fragment formation, may be a valuable indicator of the biocompatibility of dialyzer membranes. In the present in vitro study, eicosanoid generation induced by several different flat dialyzer membranes [polyacrylonitrile (PAN), cuprammonium cellulose (CC), and polycarbonate (PC)] was evaluated and compared using blood from non-uremic healthy volunteers. Generation of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) was greatest with PC followed by PAN and CC. The formation of C3a des arg with PAN was less than with either CC or PC. Our results suggest that dialyzer membranes affect complement activation and eicosanoid generation differently; biocompatibility as expressed by a low level of complement fragment formation does not necessarily translate into biocompatibility when considering eicosanoid generation.

[Analgesic consumption in the Federal Republic of Germany. The extent and the risk groups]. / Analgetika-Verbrauch in der Bundesrepublik Deutschland. Ausmass und Risikogruppen.

An analysis of still unpublished sales statistics shows that during 1976-1983 the annual sales of all analgesic package units remained relatively stable (about 115 million units per year), while the consumption of large packings mostly preferred by analgesic abusers increased from 8.13 to 11.28 million (units of 100 tablets). The annual per capita consumption of analgesic substances (1983) was 18.2 g. Among these, drugs containing salicylate and phenazone headed the list, whereas phenacetin consumption is increasingly on the downgrade (0.87 g per capita). 95% of all analgesics are used outside of the clinics. Furthermore, 80% of them are purchased on the prescription-free market. High consumption of analgesics can be assumed in 5% of the normal population. Analgesic abuse is more prevalent in women, especially in some industrial areas.

The analgesic problem in the Federal Republic of Germany: analgesic consumption, frequency of analgesic nephropathy and regional differences.

The recent withdrawal of phenacetin from the pharmaceutical market in the FRG has stimulated the discussion of the extent of analgesic abuse and analgesic nephropathy (AN). Data from wholesale statistics, given here, revealed in the FRG population a high yearly per-capita consumption of analgesics (18.2 g), mostly used in mixed compounds. According to standardized data, the FRG ranks first among the north European countries. We suggest that the prevalence data given from the EDTA-registry (4.6% of the endstage renal population) underestimates the real extent of AN. AN in the FRG shows a north-to-south decline and is most prevalent in northern areas and West Berlin. It is assumed that the analgesic dilemma in the FRG is identical to the dilemma in Switzerland and Belgium.

Amelioration of postischemic acute renal failure by prostacyclin analogue (iloprost): long-term studies with chronically instrumented conscious dogs.

The potential therapeutic value of the chemically stable carbacyclin analogue iloprost on the course of postischemic acute renal failure was studied in six conscious chronically instrumented dogs and compared with five controls. Immediately after temporary ischemia (180-min cessation of blood flow by inflation of a pneumatic cuff), the investigational group PC received a continuous intraaortal infusion of iloprost (50 ng X min-1 X kg-1) over a period of seven days, whereas the control group C received 0.9% saline. The glomerular filtration rate [( 51Cr]EDTA clearance, endogenous creatinine clearance) was less decreased in the prostacyclin analogue group than in the control group [3rd day, 18 +/- 2.5 vs. 12 +/- 1 ml X min-1 (p less than 0.05); 7th day, 23 +/- 3 vs. 12 +/- 2 ml X min-1 (p less than 0.05)]. On day 1, renal blood flow (electromagnetic flow probe) was markedly lower in the control group (129 +/- 29 ml X min-1) than in the PC group (212 +/- 29 ml X min-1; p less than 0.05), even exceeding baseline levels in the latter group. Accordingly, the excessive rise in renal vascular resistance in the control group (+136%) was abolished in the PC group (-32%; p less than 0.01). Nitrogen retention was also markedly improved. Osmolar clearance was markedly lower in the control group (0.58 +/- 0.2 ml X min-1) than in the PC group (1.41 +/- 0.17 ml X min-1; p less than 0.05). It is suggested that the beneficial effect of iloprost is mediated by preservation of renal perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)