Frequent RASSF1A promoter hypermethylation and K-ras mutations in pancreatic carcinoma

Recently, we have characterized the Ras association domain family 1A gene (RASSF1A) at the segment 3p21.3, which is frequently lost in variety of human cancers and epigenetically inactivated in many types of primary tumors, such as lung, breast, kidney, prostate and thyroid carcinomas. Here, we investigated the methylation status of the RASSF1A CpG island promoter in the pathogenesis of pancreatic cancer. RASSF1A hypermethylation was detected in 29 out of 45 (64%) primary adenocarcinomas, in 10 out of 12 (83%) endocrine tumors and in eight out of 18 (44%) pancreatitis samples. In seven out of eight pancreas cancer cell lines, RASSF1A was silenced and was retranscribed after treatment with 5-aza-2'-deoxycytidine. Additionally, we analysed the aberrant methylation frequency of cell cycle inhibitor p16(INK4a) and K-ras gene mutations in the pancreatic samples. p16 inactivation was detected in 43% of adenocarcinomas, in 17% of neuroendocrine tumors, in 18% of pancreatitis and in 63% of pancreas cancer cell lines. K-ras mutations were detected in 16 out of 45 (36%) primary adenocarcinomas. Pancreatic adenocarcinomas with K-ras mutation have significantly less RASSF1A methylation and vice versa (P=0.001, chi(2) test). In conclusion, our data indicate that inactivation of the RASSF1A gene is a frequent event in pancreatic cancer and suggest an inverse correlation between RASSF1A silencing and K-ras activation.     

Absolute dosimetry in a d(14 MeV) + Be fast neutron beam

Since 1978, the Universit?tsklinikum in Essen operates a d(14 MeV) + Be fast neutron beam for patient treatment. Dosimetric studies were performed in a rectangular 40 x 40 mm2 neutron/photon field using a transportable water calorimeter, which had been developed at the Physikalisch-Technische Bundesanstalt. The water calorimeter allowed small dosimeters to be directly calibrated in units of absorbed dose-to-water in a cylindrical phantom of 50 mm in diameter. Also, the twin detector method was applied in order to determine the photon and the neutron dose separately. By making use of a calibrated ionization chamber, the absorbed dose-to-water calibration in the cylindrical water phantom was transferred to a water phantom, a cube 300 mm on a side. Experiments and Monte Carlo calculations covering the neutron producing target, the collimator and the influence of the water calorimeter on the spectral neutron fluence at the measurement position allow the relative uncertainty of the absorbed dose-to-water determination to be reduced to 2.6% (1 SD). This direct absorbed dose-to-water determination by calorimetry has shown that the treatment planning system underestimates the physical dose to tissue by 9%. For clinical purposes, the statement of the prescribed dose had to be increased by 9% in order that the absolute absorbed dose remains constant and that the same biological endpoints are reached.     

Ranitidin und Cimetidin in der Prophylaxe der Streßulcus-Blutung: Eine prospektive Multicenter-Vergleichsstudie

Zusammenfassung In einer multizentrisch durchgeführten prospektiven Einfachblind-Studie wurde die Wirksamkeit des H₂-Blockers Ranitidin mit der von Cimetidin in der Prophylaxe streßbedingter Blutungen aus dem oberen Gastrointestinaltrakt verglichen. An dieser Studie nahmen insgesamt 380 Patienten teil. In randomisierter Anordnung erhielten 192 Patienten 4 × 50 mg Ranitidin i.v. bzw. 2 × 150 mg oral. 180 Patienten wurde 4 × 400 mg Cimetidin i.v. bzw: 1000 mg oral verabreicht. 5 Patienten unter Ranitidin (2,6%) und 12 Patienten unter Cimetidin (6,4 %) entwickelten eine obere gastrointestinale Blutung, die eindeutig oder möglicherweise auf Streßläsionen zurückzuführen war. Dieser Unterschied war nicht statistisch signifikant. Streßläsionen konnten bei 11,8 % in der Ranitidin- und bei 18,3 % in der Cimetidin-Gruppe endoskopisch nachgewiesen werden (nicht signifikant). Unter Ranitidin wurden Übelkeit, Erbrechen und Tachykardie (n = 4) und unter Cimetidin Cholestase und zentralnervöse Symptome (n = 10) registriert. Ranitidin ist somit in der Prophylaxe der Streßulcus-Blutung vergleichbar wirksam wie Cimetidin.

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Ranitidine and cimetidine in stress ulcer prophylaxis: A comparative multicentre study

Summary In a multicentre single-blind study, ranitidine was compared to cimetidine as prophylactic treatment against stress-induced upper gastrointestinal bleeding in seriously ill patients in the intensive care unit (ICU). 380 patients entered the study. 192 patients were treated with ranitidine 50 mg q.i.d. as i.v. bolus followed by 150mg orally twice daily. 188 patients received cimetidine 400 mg q.i.d. intravenously and 1,000 mg daily orally in divided doses. Five patients in the ranitidine group (2.6%) and 12 in the cimetidine group (6.4%) developed gastrointestinal bleeding definitely or possibly due to stress lesions. This difference was not significant. The incidence of stress erosions or ulcerations developing during the study was 11.8 % for the ranitidine group and 18.3% for the cimetidine group (non-significant difference). Adverse events in the ranitidine group were nausea, tachycardia or vomiting in 4 patients. 5 cimetidine-treated patients developed cholestasis, and 5 additional central nervous system problems. The high degree of efficacy of both drugs compared very favourably with the high incidence of stress ulceration and hemorrhage in similar untreated populations.

Vorläufige Ergebnisse sind in der Zeitschrift Intensivmedizin derzeit im Druck     

Der Stellenwert der konventionellen Röntgendiagnostik nach Schüller sowie der Computer- tomographie des Felsenbeins bei der präoperativen Diagnostik des Tübinger implantierbaren Kochleaverstärkers

Zusammenfassung Kürzlich wurden ein Mikrofon und ein Wandler eines intramastoidal implantierbaren Kochleaverst?rkers (CAI) zur H?rrehabilitation bei cochle?rer Schwerh?rigkeit vorgestellt. Dieses System besteht aus einem implantierbaren Mikrofon und einem implantierbaren piezoelektrischen Wandler. Es wurde bei Patienten akut implantiert. Die für eine zukünftige Indikationsstellung wichtigen Fragen lauten: 1. ob die Mastoidh?hle eines jeweiligen Patienten ausreichend Platz für ein CAI bietet und 2. ob eine pr?operative bildgebende Diagnostik pr?diktive Parameter zur Implantationseignung liefern kann. An 50 menschlichen Felsenbeinen haben wir computertomografische (CT-)Aufnahmen und R?ntgenaufnahmen nach Schüller durchgeführt und die Daten mit den Ergebnissen anschlie?ender Probeimplantationen verglichen. Unsere Ergebnisse zeigen, da? der Grad der mittels R?ntgenaufnahme nach Schüller ermittelten Pneumatisation der Warzenfortsatzzellen und der Zygomatikuszellen sowie die computertomographisch ermittelte Distanz zwischen Sinus sigmoideus und hinterer Geh?rgangswand im CT wichtige Parameter zur pr?operativen Beurteilung der Implantierbarkeit sind.      

Stomach tolerance of indomethacin derivatives: an endoscopic comparative study in healthy probands

The effect of 5 days' treatment with indomethacin, acemethacin and proglumethacin on the gastroduodenal mucosa was endoscopically evaluated in healthy volunteers. In a randomised double-blind crossover system 16 subjects received 50 mg t.i.d. indomethacin and 60 mg t.i.d. acemethacin, and a further 16 volunteers received 50 mg t.i.d. indomethacin and 150 mg t.i.d. proglumethacin. After 5 days both proglumethacin and acemethacin caused significantly less gastroduodenal lesions than indomethacin. Possible reasons for the apparently better gastro-duodenal tolerability of both indomethacin derivatives are discussed.     

Pharmacokinetics and tolerability of telenzepine in patients with compensated liver cirrhosis

Pharmacokinetics and Tolerability of Telenzepine in Patients with Chronic Liver Diseases. The pharmacokinetics and tolerability of the new selective muscarinic M1-antagonist telenzepine (BY 803; CAS 80880-90-6) were studied in 10 patients with compensated liver cirrhosis who were treated over 4 weeks with 3 mg at night. 3 mg telenzepine was well tolerated. There was no deterioration of laboratory parameters during the 4 weeks treatment course. Following a single oral dose of 3 mg telenzepine the mean maximal plasma level (cmax) averaged 5.7 (1.9-10.1) ng/ml. After repeated dosing 3 patients displayed different kinetic behaviour resulting in higher values of AUC on day 14/15 in comparison to day 1/2. tmax and cmax remained unchanged. It can be concluded that even in patients with compensated liver cirrhosis no significant accumulation of the compound will occur.     

Brain damage in preterm newborns: biological response modification as a strategy to reduce disabilities

Substances that promote the growth and maturation of oligodendrocytes and their precursors might protect against white matter injury. We suggest that neuroprotection can also be provided by such modulators of fetal and neonatal inflammatory responses as antiinflammatory cytokines, cytokine-binding proteins, and cytokine-receptor blockers. We briefly describe inflammatory responses in the fetus and newborn and show how they might contribute to brain damage. We conclude with the possibility that so-called biological response modifiers, which are drugs that modulate these inflammatory responses, might reduce the risk of brain damage and disabilities.     

Experimental modeling of the blood vessels magnetic embolization

The embolization of blood vessels is used on a large scale: the method is applied in different diseases, in the ablation of organs, but especially in tumor necrosis. The embolization can be also magnetic, if the embolus is obtained through the deposit in the vessel of magnetic nano or microparticles in the presence of an external magnetic field. The objective of our study was the modeling of the magnetic embolization using amorphous magnetic microspheres that have strong magnetic properties and are biocompatible. Experimental tests were made in order to observe the building of the magnetic embolus inside a thin spiral tube and to determine the influence of some parameters on the efficiency of occlusions: the dimensions of magnetic microspheres (1-300 mm), the debit of the liquid (4.66 - 16.5 ml/min), the viscosity of the carrier liquid (1.007 - 7.34 cSt), the direction and the intensity of the external magnetic field (340 - 600 Gs), the shape of the tube and the linear length of the deposit (5 - 50 mm). Under pre-established experimental conditions the efficiencies of occlusions were between 67% and 100%.