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Biomedical subjects

R Meier

Publications and source records attributed to R Meier.

At least 55 records · Page 3Linked to original sources
PubMed1999

Treatment of acute nonvariceal upper gastrointestinal hemorrhage.

Hospitalization for nonvariceal upper gastrointestinal hemorrhage (UGIH) is still common with an incidence of 100/100,000 adults/year. Mortality rates range between 8 and 14%. The most common etiologies of acute UGIH are gastric and duodenal ulcers which are associated with older age, Helicobacter pylori gastritis and nonsteroidal anti-inflammatory drugs. Approximately 70% of UGIH stop spontaneously, 10% bleed continuously and about 20% rebleed in the first 24-72 h. Mortality and the probability of rebleeding have been related to the ulcers' stigmata (Forrest) and to a variety of clinical findings (hematemesis, low initial hemoglobin, signs of shock, coagulopathy and liver disease). It is well established that only patients with continued bleeding or with a risk of rebleeding benefit from endoscopic or medical treatment. Endoscopic treatment (including heater probe, bipolar electrocoagulation, laser and injection therapy) control active bleeding in up to 90% and reduce significantly the rates of further bleeding, the need for blood transfusions, hospital costs and emergency surgery. Medical treatment is still controversial although positive results for somatostatin and octreotide have been found. A meta-analysis including 1,829 patients from 14 randomized trials showed the relative risk for continued bleeding or rebleeding of 0.53 (95% CI, 0.43-0.63) in favor of somatostatin and octreotide. Interventional endoscopy is the first line of treatment for UGIH. Somatostatin and its analogue octreotide may be a useful adjunct to endoscopic management or alternative when endoscopy is unsuccessful, contraindicated or unavailable.

Acute Disease↗
PubMed1999

A comparison of single fraction radiosurgery tumor control and toxicity in the treatment of basal and nonbasal meningiomas.

Between July 1993 and October 1997, 107 patients with 118 meningiomas were treated with Gamma Knife radiosurgery (GKRS). The most frequent site of tumor origin was the skull base (54%). The mean tumor diameter and volume were 2.5 cm and 9.4 cm3, respectively. The mean dose to the tumor periphery was 17 Gy, prescribed to a mean iso-dose of 47%. At a mean follow-up of 28 months, tumor control for basal and nonbasal meningiomas was 80%. Deteriorating peritumoral edema associated with symptoms was observed in 1 of 49 (2%) skull-base tumors and in 4 of 39 (10%) non-basal tumors, without associated tumor growth. (p=0.l5 and 0.234 respectively, z-test). Stereotactic radiosurgery can achieve acceptable tumor control with low morbidity in the treatment of most meningiomas. However, when the tumor is nonbasal, the potential morbidity from peritumoral edema should be recognized and other treatment options considered, such as adjuvant surgery, partial fractionated irradiation or stereotactic radiotherapy.

Adolescent↗
PubMed1999

Is carbon dioxide (CO2) a useful short acting anaesthetic for small laboratory animals?

The anaesthetic effect of carbon dioxide (CO2) was investigated under predetermined exposure times in rats, mice and guinea pigs with admixture of 20% of oxygen (O2), and with 20% of ambient air in rats. In rats first symptoms (median) were detectable between 7 and 9.5 s, the induction time (median) varied between 16 and 20.5 s and the surgical tolerance (median) was 40 s (after 60 s of exposure) and 53.5 s (after 120 s of exposure) to 80% CO2/20% O2. When O2 was replaced by ambient air, a surgical tolerance of 53.5 s (after 60 s of exposure) and 77 s (after 120 s of exposure) was measured. In mice the induction time to 80% CO2/20% O2 was 10 s and the surgical tolerance 19.5 s (after 120 s of exposure). Guinea pigs showed an induction period of 20 s and a surgical tolerance of 50 s (after 30 s of exposure) to 80% CO2/O2. Recovery was short and smooth in all species. This method of general anaesthesia seems to be suitable for short and painful interventions, mainly in rats, but also in guinea pigs.

Anesthesia, Inhalation↗
PubMed1999

The Domestic/International Gastroenterology Surveillance Study (DIGEST): design, subjects and methods.

BACKGROUND: The Domestic/International Gastroenterology Surveillance Study (DIGEST) was designed to examine the 3-month prevalence of upper gastrointestinal (GI) symptoms internationally and the impact of these symptoms on healthcare usage and quality of life. METHODS: The study sample was derived from the urban, adult (> or = 18 years) population of Canada, Italy, Japan, The Netherlands, Switzerland, the USA and the Nordic countries (Denmark, Finland, Norway and Sweden). Subjects were randomly recruited on a house-to-house basis in all countries except the USA and Italy, where telephone recruitment was carried out. Participants were interviewed in their own homes (house-to-house recruitment) or at a central location (telephone recruitment). The DIGEST questionnaire consisted of two sections. The first was a newly developed questionnaire consisting of 27 questions examining the prevalence, frequency and severity of upper GI symptoms, and their impact on healthcare use and daily activities. It also examined a number of demographic and socioeconomic variables. This part of the questionnaire was evaluated and pilot-tested before commencement of the survey. The second part of the questionnaire consisted of the local language version of the Psychological General Well-Being Index (PGWBI), a validated generic quality-of-life scale. Following completion of the survey, subjects with upper GI symptoms were classified on the basis of their most bothersome symptom into three symptom groups: gastro-oesophageal reflux-like, ulcer-like or dysmotility-like. CONCLUSIONS: Rigorous design, standardization of interview techniques and prior evaluation of the DIGEST questionnaire, provided a firm foundation for reliable data collection, analysis and interpretation.

Adult↗
PubMed1999

Neoadjuvant Androgen Ablation Combined with External-Beam Radiation Therapy and Permanent Interstitial Brachytherapy Boost in Localized Prostate Cancer.

Androgen ablation therapy has been combined with permanent interstitial brachytherapy in order to downsize the gland prior to seed implantation. It also has been employed in an attempt to improve the effectiveness of therapy in patients with a poor prognosis. We report on 50 patients consecutively treated and prospectively followed. All received neoadjuvant hormonal therapy (NHT) and 45 Gy of external-beam therapy to a limited pelvic field, followed by permanent implantation of (125)I or (103)Pd seeds. The median follow-up is 42.1 months (range 9.0-90.8 months). The prostate specific antigen (PSA) progression-free survival rate (<1.0 ng/mL) was 76% at 5 years (Kaplan-Meier method). Local control was achieved in 100% of the patients and distant disease-free survival in 85%. High-risk patients treated contemporaneously with these patients, who received external-beam radiation and a seed boost without NHT, had a 62% rate of 5-year PSA progression-free survival. Although the modest improvement in PSA progression-free survival is not statistically significant at 5 years (P = 0.5), the patients treated with NHT in addition to combined radiotherapy presented with significantly higher serum PSA concentrations (mean 21.0 ng/mL; median 17.0 ng/mL) than those treated with combination radiotherapy alone (mean 15.6 ng/mL; median 10.6 ng/mL) and thus had a worse prognosis.

Journal Article↗
PubMed1998

Inactivation and dephosphorylation of protein kinase Balpha (PKBalpha) promoted by hyperosmotic stress.

To study the role of protein kinase B (PKB) in response to cellular stress, we examined PKBalpha activity following different stress treatments. Hyperosmotic but not chemical stress resulted in inactivation of PKBalpha and prevented activation by pervanadate and mitogens. Hyperosmotic shock did not affect the MAP kinase pathway, suggesting that this inhibitory effect was specific for PKB. Our data further indicate that downregulation occurs via dephosphorylation of Thr308 and Ser473, the major regulatory phosphorylation sites of PKBalpha. Indeed, calyculin A, which inhibits protein phosphatases 1 and 2A, effectively blocked hyperosmotic stress-mediated inactivation (dephosphorylation) of PKBalpha. High osmolarity did not affect phosphatidylinositol 3-kinase activity but led to a marked increase in PI(3,4,5)P3 and a decrease in PI(3,4)P2 formation after pervanadate stimulation, suggesting that hyperosmotic stress has an inhibitory effect on a phosphatidylinositol 5-phosphatase which converts PI(3,4,5)P3 into PI(3,4)P2. Immunofluorescence studies revealed that membrane translocation, a prerequisite for PKB activation, was not affected by hyperosmotic stress. Our results indicate that hyperosmotic stress can act at two levels: (i) inhibition of phosphorylation of Thr308 and Ser473 by upstream kinases and (ii) by promoting rapid dephosphorylation of these regulatory sites.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed1998

[Difficulties in differentiation between Crohn disease and ulcerative colitis].

We report on the medical history of a 44 year old woman, who has been diagnosed to suffer from ulcerative colitis, first diagnosed in 1991. Until 1994, when she had finally a colectomy, recurrent episodes occurred under full medical treatment. After colectomy the diagnosis had to be revised as histology revealed Crohn's disease. Only a few months after surgery a new episode of Crohns disease developed including the occurrence of an anal fistula.

Adult↗
PubMed1998

[Validation of the "Digest Questionnaire" for consistency and reproducibility with reference to upper abdominal symptoms].

"Digest" is a international effort to record the prevalence of digestive symptoms in the general population. The international questionnaire was tested in German translation for reliability and reproducibility. The questionnaire consists of 14 symptoms, which were investigated by standardized questions. Each symptom was described in 3 dimensions: frequency, severity and impact on daily activities. 127 successive patients referred for upper gastrointestinal endoscopy were interviewed twice by a young assistant and by an experienced gastroenterologist before the diagnostic work-up. A further 72 volunteers served as a control group. In these volunteers no upper gastrointestinal endoscopy was performed. Reliability and reproducibility were calculated by the Spearman rank test. The most frequent diagnoses were: organic diseases (oesophagitis [28], gastric ulcer/erosive gastritis [32] and duodenal ulcer [18]); functional diseases (dyspepsia [32] and irritable bowel syndrome [14]). Reproducibility was satisfactory by accepted standards (p > 0.7). Reliability was very good, with r-values for each symptom between p 0.96-0.99. The impact on daily activities was highest in the case of heart-burn or localized upper gastrointestinal pain, and lowest in the case of belching and fullness. The questionnaire can be easily administered by the non-specialist and the results discriminate well between functional/organic diseases and healthy people, thanks to excellent reproducibility and reliability.

Activities of Daily Living↗
PubMed1998

Deuterium in comet C/1995 O1 (Hale-Bopp): detection of DCN.

Deuterated hydrogen cyanide (DCN) was detected in a comet, C/1995 O1 (Hale-Bopp), with the use of the James Clerk Maxwell Telescope on Mauna Kea, Hawaii. The inferred deuterium/hydrogen (D/H) ratio in hydrogen cyanide (HCN) is (D/H)HCN = (2.3 +/- 0.4) x 10(-3). This ratio is higher than the D/H ratio found in cometary water and supports the interstellar origin of cometary ices. The observed values of D/H in water and HCN imply a kinetic temperature >/=30 +/- 10 K in the fragment of interstellar cloud that formed the solar system.

Deuterium↗
PubMed1998

A determination of the HDO/H2O ratio in comet C/1995 O1 (Hale-Bopp).

Deuterated water (HDO) was detected in comet C/1995 O1 (Hale-Bopp) with the use of the James Clerk Maxwell Telescope on Mauna Kea, Hawaii. The inferred D/H ratio in Hale-Bopp's water is (3.3 +/- 0.8) x 10(-4). This result is consistent with in situ measurements of comet P/Halley and the value found in C/1996 B2 (Hyakutake). This D/H ratio, higher than that in terrestrial water and more than 10 times the value for protosolar H2, implies that comets cannot be the only source for the oceans on Earth.

Deuterium Oxide↗
PubMed1998

Nerve growth factor promotes activation of the alpha, beta and gamma isoforms of protein kinase B in PC12 pheochromocytoma cells.

The activation of phosphatidylinositol (PtdIns) 3-kinase is considered to be a key event occurring after stimulation of cells with growth factors. The proto-oncogenic protein kinase B (PKB; also known as RAC protein kinase or Akt) has recently been shown to be a downstream target of PtdIns 3-kinase and may be involved in cell survival. We therefore asked whether stimulation of neuronal cells with nerve growth factor (NGF), on which certain types of neurons are dependent for survival, causes activation of PKB. Stimulation of serum-starved PC12 rat pheochromocytoma cells with NGF caused an increase of up to 14-fold in PKB activity. This activation was detected within 1 min of stimulation and occurred at NGF concentrations that are consistent with TrkA-mediated signaling. PKB activation was accompanied by a decrease in electrophoretic mobility of the kinase, which is characteristic of phosphorylation. Both PKB activation and mobility changes were prevented by wortmannin, indicating the upstream involvement of PtdIns 3-kinase in these events. Analyses employing isoform-specific antibodies for immunoprecipitation suggested that all three isoforms of PKB (alpha, beta and gamma) are activated in response to NGF. G-protein-coupled-receptor agonists, lysophosphatidic acid (lyso-PtdH) and thrombin, which induce rapid neurite retraction, neither stimulated PKB activity, nor affected NGF-induced or insulin-induced kinase activation. Wortmannin treatment did not prevent neurite retraction induced by lyso-PtdH or thrombin. These data suggest that PtdIns 3-kinase and PKB are not involved in cytoskeletal changes mediated by the small GTPase Rho.

Androstadienes↗
PubMed1998

Phylogeny of fungus-growing ants (Tribe Attini) based on mtDNA sequence and morphology.

We examined the phylogenetic relationships among taxa of attine or "fungus-growing" ants (Tribe Attini) using parsimony analyses of molecular and morphological data. We sequenced a region of mitochondrial DNA from 13 taxa of attines and from one closely related outgroup species, Wasmannia auropunctata. Our study sequence included the 3' end of the cytochrome c oxidase subunit I (CO I) locus (183 to 198 total sites; 91 informative sites), an intergenic spacer region of variable size (0 to 152 sites), the tRNA leucine locus (65 to 74 sites), and the 5' end of the cytochrome c oxidase subunit II (co II) locus (292 total sites; 140 informative sites). The inferred relationships among the attine taxa based on an unweighted analysis of the nucleotide sequence data closely matched the relationships inferred from an analysis of larval morphological characters from 11 of the taxa. In fact, the inferred relationships were completely congruent among the protein parsimony analysis of amino acid data, the morphology analysis, and "total evidence" analysis combining the amino acid and morphology data. The congruent conclusions we obtained from two independent data sets increases our confidence in the reliability of our analyses.

Animals↗
PubMed1998

Effects of a partially hydrolyzed guar gum on intestinal absorption of carbohydrate, protein and fat: a double-blind controlled study in volunteers.

UNLABELLED: Some dietary fibres have been shown to affect the rate of absorption of dietary carbohydrate, protein and fat as well as exocrine pancreatic function. The aim of the study was to examine the effect of partially hydrolysed guar gum (BENEFIBER), on normal absorption of glucose, amino acid (arginine) and fat. In addition hepatic, pancreatic, renal and haematological side effects were evaluated. METHODS: A double blind, randomized and cross-over design was used. Each subject served as its own control. Ten healthy male volunteers participated in the study. Each subject was randomly assigned to two different dietary regimes for a period of 7 days each. The study was repeated with the other diet for another 7-day period after an interval of at least 1 week. In one study period the subjects took liquid formula diet without fibre and during the other study period they took the same diet with fibre. RESULTS: The results of the study demonstrated that BENEFIBER did apparently not interfere with the normal absorption of glucose, amino acid and fat. In keeping with these observations, insulin release and exocrine pancreatic function were not affected. Haematological, renal and hepatic toxicity were not observed in association with BENEFIBER consumption. CONCLUSION: We conclude that BENEFIBER is a safe source of soluble fibre.

Adult↗
PubMed1998

Effect of transdermal application of nicotine on colonic transit in healthy nonsmoking volunteers.

The radio-opaque marker technique (ROMT) is a safe and noninvasive method to determine total colonic (TCTT) and segmental colonic transit times (SCTT). Previous results have shown that smoking volunteers had significantly longer TCTT than nonsmokers, but the underlying mechanism was not clear. We investigated the effect of transdermal nicotine application in two different doses in a non-blind randomized experiment involving three distinct phases. In phase 1 baseline transit times were determined with an abdominal X-ray after a 6-day period of marker ingestion and again after the following bowel movement to study the influence of a bowel movement just before the X-ray. TCTT was nearly twice as high before than after defaecation (42.6 h vs. 25.1 h, P < 0.05). The main acceleration was found in the rectosigmoid (RS) (18.6 h vs 7.1 h, P < 0.05) with no significant changes in right (RC) and left colon (LC). In phase 2 and 3 nicotine was applied in two doses of 17.5 mg day-1 and 35 mg day-1 in random order. Both doses resulted in a significant decrease of TCTT compared to the predefaecation baseline (42.6 h vs 32.2 h/28.2 h, respectively, P < 0.05). Again the main effect was located in the RS (18.6 h vs 9.9 h/7.6 h, P < 0.05). Short-term application nicotine results in a decrease of TCTT which is due to an accelerated transit in the RS.

Administration, Cutaneous↗
PubMed1997

Role of translocation in the activation and function of protein kinase B.

We have investigated the role of subcellular localization in the regulation of protein kinase B (PKB) activation. The myristoylation/palmitylation motif from the Lck tyrosine kinase was attached to the N terminus of protein kinase B to alter its subcellular location. Myristoylated/palmitylated (m/p)-PKBalpha was associated with the plasma membrane of transfected cells, whereas the wild-type kinase was mostly cytosolic. The activity of m/p-PKBalpha was 60-fold higher compared with the unstimulated wild-type enzyme, and could not be stimulated further by growth factors or phosphatase inhibitors. In vivo 32P labeling and mutagenesis demonstrated that m/p-PKBalpha activity was due to phosphorylation on Thr308 and Ser473, that are normally induced on PKB following stimulation of the cells with insulin or insulin-like growth factor-1 (IGF-1). A dominant negative form of phosphoinositide 3-kinase (PI3-K) did not affect m/p-PKBalpha activity. The pleckstrin homology (PH) domain of m/p-PKBalpha was not required for its activation or phosphorylation on Thr308 and Ser473, suggesting that this domain may serve as a membrane-targeting module. Consistent with this view, PKBalpha was translocated to the plasma membrane within minutes after stimulation with IGF-1. This translocation required the PH domain and was sensitive to wortmannin. Our results indicate that PI3-K activity is required for translocation of PKB to the plasma membrane, where its activation occurs through phosphorylation of the same sites that are induced by insulin or IGF-1. Following activation the kinase detached from the membrane and translocated to the nucleus.

Amino Acid Substitution↗