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Biomedical subjects

R Meier

Publications and source records attributed to R Meier.

At least 37 records · Page 2Linked to original sources
PubMed2001

Mesalazine 4 g daily given as prolonged-release granules twice daily and four times daily is at least as effective as prolonged-release tablets four times daily in patients with ulcerative colitis.

BACKGROUND: High doses of mesalazine usually result in an inconvenient dosage schedule and reduced compliance. The goal of this trial was to compare the effects of mesalazine 4 g daily given as prolonged-release granules in packets of 1 g with that of prolonged-release tablets of 0.5 g. METHODS: Two hundred twenty-seven patients with mild-to-moderate ulcerative colitis were randomized to treatment with two packets twice daily (Gr-b.i.d.), 1 packet four times daily (Gr-q.i.d.) or 2 tablets four times daily (Ta-q.i.d.) for 8 weeks. A disease activity index (ulcerative colitis disease activity index: UC-DAI) was calculated, and the granules were defined as noninferior to the tablets if the lower limit of the 95% CI for the differences was more than -1 UC-DAI score unit. RESULTS: Noninferiority of the granules compared with the tablets was demonstrated. The mean improvement in the UC-DAI in the treatment groups Gr-b.i.d., Gr-q.i.d., and Ta-q.i.d. were 3.2, 2.9, and 2.4, respectively; the proportion of complete responders in the three groups 39%, 37%, and 31%, respectively. There were no differences in side effects. CONCLUSION: Mesalazine 4 g daily given as prolonged-release granules twice and four times daily is at least as effective as prolonged-release tablets four times daily in patients with mild to moderate ulcerative colitis. The patients preferred the twice daily dosing.

Adolescent↗
PubMed2001

The use of silymarin in the treatment of liver diseases.

The high prevalence of liver diseases such as chronic hepatitis and cirrhosis underscores the need for efficient and cost-effective treatments. The potential benefit of silymarin (extracted from the seeds of Silybum marianum or milk thistle) in the treatment of liver diseases remains a controversial issue. Therefore, the objective of this review is to assess the clinical efficacy and safety of silymarin by application of systematic approach. 525 references were found in the databases, of which 84 papers were retained for closer examination and 36 were deemed suitable for detailed analysis. Silymarin has metabolic and cell-regulating effects at concentrations found in clinical conditions, namely carrier-mediated regulation of cell membrane permeability, inhibition of the 5-lipoxygenase pathway, scavenging of reactive oxygen species (ROS) of the R-OH type and action on DNA-expression, for example, via suppression of nuclear factor (NF)-kappaB. Pooled data from case record studies involving 452 patients with Amanita phalloides poisoning show a highly significant difference in mortality in favour of silibinin [the main isomer contained in silymarin] (mortality 9.8% vs 18.3% with standard treatment; p < 0.01). The available trials in patients with toxic (e.g. solvents) or iatrogenic (e.g. antispychotic or tacrine) liver diseases, which are mostly outdated and underpowered, do not enable any valid conclusions to be drawn on the value of silymarin. The exception is an improved clinical tolerance of tacrine. In spite of some positive results in patients with acute viral hepatitis, no formally valid conclusion can be drawn regarding the value of silymarin in the treatment of these infections. Although there were no clinical end-points in the four trials considered in patients with alcoholic liver disease, histological findings were reported as improved in two out of two trials, improvement of prothrombin time was significant (two trials pooled) and liver transaminase levels were consistently lower in the silymarin-treated groups. Therefore, silymarin may be of use as an adjuvant in the therapy of alcoholic liver disease. Analysis was performed on five trials with a total of 602 patients with liver cirrhosis. The evidence shows that, compared with placebo, silymarin produces a nonsignificant reduction of total mortality by -4.2% [odds ratio (OR) 0.75 (0.5 - 1.1)]; but that, on the other hand, the use of silymarin leads to a significant reduction in liver-related mortality of-7% [OR: 0.54 (0.3 - 0.9); p < 0.01]. An individual trial reported a reduction in the number of patients with encephalopathy of -8.7% (p = 0.06). In one study of patients with cirrhosis-related diabetes mellitus, the insulin requirement was reduced by -25% (p < 0.01). We conclude that available evidence suggests that silymarin may play a role in the therapy of (alcoholic) liver cirrhosis. Silymarin is has a good safety record and only rare case reports of gastrointestinal disturbances and allergic skin rashes have been published. This review does not aim to replace future prospective trials aiming to provide the 'final' evidence of the efficacy of silymarin.

Alcoholism↗
PubMed2000

Protein kinase B beta/Akt2 plays a specific role in muscle differentiation.

Insulin-like growth factors positively regulate muscle differentiation through activation of the phosphatidylinositol 3-kinase/protein kinase B (PKB/Akt) signaling pathway. Here, we compare the role of the two closely related alpha (Akt1) and beta (Akt2) isoforms of PKB in muscle differentiation. During differentiation of C2.7 or L6D2 myoblasts, PKBbeta was up-regulated whereas expression of PKBalpha was unaltered. Although the two isoforms were found active in both myoblasts and myotubes, cell fractionation experiments indicated that they displayed distinct subcellular localizations in differentiated cells with only PKBbeta localized in the nuclei. In a transactivation assay, PKBbeta (either wild-type or constitutively active) was more efficient than PKBalpha in activating muscle-specific gene expression. Moreover, microinjection of specific antibodies to PKBbeta inhibited differentiation of muscle cells, whereas control or anti-PKBalpha antibodies did not. On the other hand, microinjection of the anti-PKBalpha antibodies caused a block in cell cycle progression in both non muscle and muscle cells, whereas anti-PKBbeta antibodies had no effect. Taken together, these results show that PKBbeta plays a crucial role in the commitment of myoblasts to differentiation that cannot be substituted by PKBalpha.

Cell Differentiation↗
PubMed2000

Germline alterations in the cyclooxygenase-2 gene are not associated with the development of extracolonic manifestations in a large swiss familial adenomatous polyposis kindred.

Familial adenomatous polyposis (FAP) is an autosomal dominant condition leading to the development of multiple colorectal polyps and other features. Intrafamilial variation in phenotype is known to occur in FAP; despite carrying the same causing mutation in the APC gene, disease expression may considerably differ in affected individuals, likely due to the existence of modifier genes. Several lines of evidence suggest the cyclooxygenase-2 (COX-2) gene to be a candidate modifier in FAP. Since COX-2 appears to be expressed in tissues prone to be affected in FAP, it might influence the occurrence of extracolonic manifestations in this disorder. Herein, we investigated whether alterations in the COX-2 gene are involved in the development of extracolonic polyps and extragastrointestinal features. Mutational analysis using single-strand conformation polymorphism (SSCP) in 130 members of a FAP family displaying strong phenotype variation revealed 3 polymorphic sites within the coding region of the COX-2 gene. None of these allelic variants, however, segregated with a particular disease phenotype. In addition, expression analysis was performed in 31 family members with representative phenotypes. Neither of the two polymorphisms detected within the COX-2 promoter was associated with a given phenotype nor was there a significant difference in quality or quantity of COX-2 mRNA in lymphocytes as measured by reverse transcription- and real time quantitative reverse transcription PCR (RT-PCR and TaqMan). In conclusion, germline alterations in the COX-2 gene are unlikely to account for the development of extracolonic disease in FAP patients.

Adenomatous Polyposis Coli↗
PubMed2000

Magnetic splitting of valence states in ferromagnetic and antiferromagnetic lanthanide metals

The magnetic splitting of Delta(2) valence states in the heavy lanthanide metals Gd, Tb, Dy, and Ho was studied in epitaxial films by angle-resolved photoemission, revealing an essentially Stoner-like temperature dependence in all cases. It scales linearly with the 4f spin moment, even in the case of the helical antiferromagnet Ho. Such a behavior can be explained by a substantial localization of the corresponding wave function in the c direction. The helical magnetic structure was confirmed for the thin Ho films by in situ resonant magnetic x-ray diffraction.

Journal Article↗
PubMed2000

Partially hydrolyzed guar gum-supplemented oral rehydration solution in the treatment of acute diarrhea in children.

BACKGROUND: Partially hydrolyzed guar gum (Benefiber; Novartis Nutrition, Minneapolis, MN, U.S.A.) is fermented by colonic bacteria liberating short-chain fatty acids (SCFAs), which accelerate colonic absorption of salt and water. The purpose of this study was to evaluate the effect of Benefiber (BF)-supplemented World Health Organization Oral Rehydration Solution (WHO ORS) in the treatment of acute noncholera diarrhea in children. METHODS: A double-blind, randomized, controlled clinical trial was performed at ICDDR,B in 150 male children aged 4 to 18 months who had watery diarrhea of less than 48 hours' duration. After admission, children were assigned to receive either WHO ORS or BF-supplemented WHO ORS until recovery. Major outcome measures, such as duration of diarrhea and amount of stool output, were compared between the treatment groups. RESULTS: Patients receiving BF-supplemented WHO ORS had significantly reduced duration of diarrhea compared with the control group (mean +/- SD, 74 +/- 37 vs. 90 +/- 50 hours, P = 0.03). Survival analysis for duration of diarrhea also showed a reduction the BF-supplemented WHO ORS-treated group (P = 0.025, log rank test). There was also less stool output daily from days 2 through 7 in the patients treated with BF-supplemented WHO ORS compared with that in the children treated with WHO ORS; the reduction was significant on day 7 only. CONCLUSION: Benefiber added to standard WHO ORS substantially reduces the duration of diarrhea and modestly reduced stool output in acute noncholera diarrhea in young children, indicating its potential as a new antidiarrheal therapy for acute diarrhea in children.

Acute Disease↗
PubMed2000

Induction of artificial fat maldigestion by tetrahydrolipstatin assessed by the (13)C-hiolein breath test in healthy volunteers. A double-blind controlled pilot study.

BACKGROUND: (13)C-hiolein is a purified algal triglyceride which is synthesized with 98% of all carbon atoms of the molecule uniformly (13)C-labeled. Orlistat is the new name for tetrahydrolipstatin (THL), which is a specific and potent inhibitor of gastrointestinal lipases which induces artificial fat malabsorption in humans. The aim of the present study was to use the (13)C-hiolein breath test (HBT) to assess THL-induced fat malabsorption in healthy volunteers. METHODS: Eight healthy volunteers of normal body weight underwent 2 study periods of 4 days of diet with or without THL 120 mg t.i.d. On day 5, a HBT was performed. (13)CO(2) recovery in breath samples was measured over 24 h by isotope ratio mass spectrometry. RESULTS: The peak (13)CO(2) excretion occurred only after 5 h in both treatment groups with little difference during the first 4 h between the groups. THL potently reduced fat digestion and absorption with the most pronounced effect observed after 8 h: 1.1+/-0.2 vs. 2.3+/-0.3% dose in control experiments (p<0.05). The 24-hour cumulative (13)CO(2) excretion was also significantly reduced by THL: 14.9+/-2.2 vs. 28.4+/-4.1% dose in control experiments (p<0.05). In 6 of the 8 subjects, the cumulative (13)CO(2) excretion was lower with THL 120 mg t.i.d. than with placebo. CONCLUSION: The HBT well reflects THL-induced artificial fat maldigestion in healthy volunteers.

Adult↗
PubMed2000

Short-course androgen ablation combined with external-beam radiation therapy and low-dose-rate permanent brachytherapy in early-stage prostate cancer: a matched subset analysis.

BACKGROUND AND PURPOSE: In order to evaluate the effect of short-term androgen blockade on biochemical control rates for high-risk patients receiving a combination regimen of external-beam radiation therapy and low-dose-rate permanent seed implant brachytherapy, a retrospective matched subset analysis was performed. PATIENTS AND METHODS: Inclusion in the high-risk cohort required at least two of the following poor prognostic factors: serum prostate specific antigen (PSA) concentration > or = 10.0 ng/mL, Gleason score > or = 7, or clinical stage T(2c) or T(3a) disease. Twenty-one patients who underwent androgen ablation between June 1991 and December 1995 in addition to combined-modality radiation therapy qualified as high risk, as did 77 patients who underwent combined-radiation therapy only. There was no statistically significant difference between the two groups in terms of follow-up (mean 44.6 v 47.8 months, respectively), pretreatment PSA, clinical stage, biopsy Gleason score, or the presence of all three poor prognostic factors. RESULTS: The overall rates of freedom from biochemical failure at 5 years were 77% in the hormonally treated group and 58% in the nonhormonally treated group. The difference was not statistically significant by log rank test (P = 0.08). CONCLUSION: Longer follow-up with larger patient numbers is needed to define the role of adjuvant androgen ablation combined with radiation therapy.

Androgen Antagonists↗
PubMed1999

Effects of intradialytic parenteral nutrition in chronic haemodialysis patients with malnutrition: a pilot study.

BACKGROUND AND AIMS: Protein and calorie malnutrition is frequently observed in chronic haemodialysis (HD) patients. Recently it has been suggested that intradialytic nutritional support with amino acids may improve nutritional status and increase immunocompetence. The aim of this study was to evaluate the effects of intradialytic infusion of amino acids, lipids and glucose on body composition and other parameters of nutritional status in patients undergoing HD. METHODS: Seven patients with a mean age of 77 +/- 6 years (range, 60-86 years), a mean BMI of 20.1 +/- 2.8 (range, 16.1-24.4) and clinical signs of malnutrition participated in the study (mean time on HD, 51 +/- 36 months). HD was performed 12 hours per week with bicarbonate as a buffer and a polysulfon capillary dialyzer (F-60). During the 3-month period of intervention the patients received an intradialytic parenteral solution during the regular scheduled dialysis treatment, containing amino acids (12 g s/h), a glucose 15% solution (37.5 g/h) and a fat emulsion (12.5 g/h). RESULTS: (mean +/- SEM) Total calorie intake increased from 1550 +/- 63 to 2255 +/- 114 (kcal/24 h) p < 0.01, during the intervention period and body weight increased from 49.9 +/- 5.9 to 51.9 +/- 5.7 kg (p < 0.005). Fat mass and lean body mass (bioelectrical impedance analysis, BIA) increased from 13.2 +/- 2.6 to 14.2 +/- 2.6 (p < 0.02) and from 36.9 +/- 3.2 to 37.9 +/- 3.2 kg (p < 0.003), respectively. Plasma concentrations of albumin, total protein, transferrin, leptin IGF-I, IGFBP-3 and the protein catabolic rate remained unchanged. CONCLUSIONS: Supplementary intravenous intradialytic nutrition in chronic HD patients with malnutrition increased total body weight by effecting equivalent increases in lean body and fat masses.

Aged↗
PubMed1999

Cometary deuterium.

Deuterium fractionations in cometary ices provide important clues to the origin and evolution of comets. Mass spectrometers aboard spaceprobe Giotto revealed the first accurate D/H ratios in the water of Comet 1P/Halley. Ground-based observations of HDO in Comets C/1996 B2 (Hyakutake) and C/1995 O1 (Hale-Bopp), the detection of DCN in Comet Hale-Bopp, and upper limits for several other D-bearing molecules complement our limited sample of D/H measurements. On the basis of this data set all Oort cloud comets seem to exhibit a similar (D/H)H2O ratio in H2O, enriched by about a factor of two relative to terrestrial water and approximately one order of magnitude relative to the protosolar value. Oort cloud comets, and by inference also classical short-period comets derived from the Kuiper Belt cannot be the only source for the Earth's oceans. The cometary O/C ratio and dynamical reasons make it difficult to defend an early influx of icy planetesimals from the Jupiter zone to the early Earth. D/H measurements of OH groups in phyllosilicate rich meteorites suggest a mixture of cometary water and water adsorbed from the nebula by the rocky grains that formed the bulk of the Earth may be responsible for the terrestrial D/H. The D/H ratio in cometary HCN is 7 times higher than the value in cometary H2O. Species-dependent D-fractionations occur at low temperatures and low gas densities via ion-molecule or grain-surface reactions and cannot be explained by a pure solar nebula chemistry. It is plausible that cometary volatiles preserved the interstellar D fractionation. The observed D abundances set a lower limit to the formation temperature of (30 +/- 10) K. Similar numbers can he derived from the ortho-to-para ratio in cometary water, from the absence of neon in cometary ices and the presence of S2. Noble gases on Earth and Mars, and the relative abundance of cometary hydrocarbons place the comet formation temperature near 50 K. So far all cometary D/H measurements refer to bulk compositions, and it is conceivable that significant departures from the mean value could occur at the grain-size level. Strong isotope effects as a result of coma chemistry can be excluded for molecules H2O and HCN. A comparison of the cometary (D/H)H2O ratio with values found in the atmospheres of the outer planets is consistent with the long-held idea that the gas planets formed around icy cores with a high cometary D/H ratio and subsequently accumulated significant amounts of H2 from the solar nebula with a low protosolar D/H.

Deuterium↗
PubMed1999

The cardiac endothelin system in established pressure overload left ventricular hypertrophy.

In normal hearts, endothelin-1 (ET-1) has been shown to initiate myocyte growth and to modulate cardiac function. However, regulation of the various components of the system and the functional effects of ET-1 in established left ventricular hypertrophy (LVH) are less clear. We thus studied ET-1, ET(A) receptor, and endothelin converting enzyme (ECE-1) mRNA regulation as well as the effects of ET-1 on coronary resistance, LV contractility and relaxation in hypertrophied rat hearts. Cardiac pressure overload, secondary to banding of the ascending aorta, resulted in a transient increase of cardiac ET-1 and ET(A) receptor mRNAs that reached a maximum at 2 days (+75% and +40%, respectively, P<0.05, each). ET-1 mRNA levels reached a second peak at 84 days of pressure overload (+60%, P<0.05), at the later time point in conjunction with elevated ECE-1 mRNA levels (+20%, P<0.05). The functional implications of ET-1 were examined in a study of isolated perfused hearts. Both hearts with established LVH and sham control hearts responded to ET-1 perfusion (10(-1)] to 10(-9) M) with an increase of coronary perfusion pressure (CPP; +85+/-15 and +75+/-8 mm Hg; P<0.001 each) and a slight decrease of LV systolic pressure (LVP; -12+/-9 and -9+/-7 mm Hg; P = NS). In contrast, ET-1 increased LV end-diastolic pressure (LVEDP) only in LVH hearts (+22+/-7 mm Hg, P<0.05 versus baseline and +20+/-7 mm Hg, P<0.05 versus sham). Direct stimulation of protein kinase C mimicked the effects of ET-1, whereas inhibition of this kinase or the Na+ -H+ exchanger blunted the effects of ET-1 on CPP, LVP, and LVEDP. Interestingly, coadministration of the vasodilator and the nitric oxide (NO) donor nitroglycerin not only prevented the increase of CPP and LVEDP, but also uncovered a slight positive inotropic effect of ET-1 in LVH hearts. Thus, the cardiac expression of ET-1, ET(A), and ECE-1 mRNAs displays a distinct pattern during early and advanced cardiac pressure overload. Furthermore, ET-1 mediates a slight depression of systolic, and a profound depression of diastolic, functional parameters in hearts with established LVH, effects that appear to be secondary to ET-1-related coronary vasoconstriction. The data suggest a functional role of the endothelin system in hearts with established pressure overload hypertrophy.

Amiloride↗