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Biomedical subjects

B Schmid

Publications and source records attributed to B Schmid.

At least 19 recordsLinked to original sources
PubMed2003

[Incompatibility reactions in the intensive care unit. Five years after the implementation of a simple "colour code system"].

In intensive care units (ICU) most of the drugs have to be administered by y-piece infusions or admixtures. Drug stability and compatibility are critical elements in the accurate and appropriate delivery of drug therapies to patients. Five years after the implementation of a simple "colour code system" in an attempt to minimize the number of incompatibilities, the situation has been re-examined. The clinical pharmacist collected 78 different medication regimes and the compatibility and incompatibilities were evaluated based on the available literature. Before initiating the "colour code system" in the ICU, 15% of the administered drugs were incompatible and afterwards the number decreased to 2%. This rate could be kept at 2%, even 5 years after the implementation of the system,without any further intervention. As a result of teamwork between nurses, doctors and clinical pharmacy a simple "colour system" was established to minimize incidences of drug incompatibility in the ICU. The system is highly accepted because the degree of uncertainty has been considerably reduced.

Color↗
PubMed2003

Effective number of breeders and maintenance of genetic diversity in the captive bearded vulture population.

We combined pedigree data with data derived from 14 microsatellite loci to investigate genetic diversity and its maintenance in the captive source population for the reintroduction of the bearded vulture into the Alps. We found the captive population to be genetically more variable than the largest natural population in Europe, both in terms of mean number of alleles per locus and mean observed and expected heterozygosity. Allelic diversity of the captive population was higher than, and mean heterozygosity measurements were comparable with the ones found in two large, extinct populations from Sardinia and the Alps represented by museum specimens. The amount of genetic variability recruited with the founders was still present in the captive population of the year 2000, mainly because the carriers of rare alleles were still alive. However, the decline in expected heterozygosity and the loss of alleles over generations in captivity was significant. Point estimates of effective population size, N(e), based on pedigree data and estimates of effective number of breeders, N(b), based on allele frequency changes, ranged from 20 to 30 and were significantly smaller than the census size. The results demonstrate that the amount of genetic variability in the captive bearded vulture population is comparable or even larger than the amount present in natural populations. However, the population is in danger to lose genetic variability over time because of genetic drift. Management strategies should therefore aim at preserving genetic variability by minimising kinship, and at increasing N(e) by recruiting additional founders and enhancing gene flow between the released, the captive and natural populations.

Alleles↗
PubMed2002

Busulfan, cyclophosphamide, and etoposide as high-dose conditioning regimen in patients with malignant lymphoma.

We investigated the efficacy and toxicity of the combination of busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP-16) as a preparative regimen prior to autologous hematopoietic stem cell transplantation (ASCT) in patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL). Fifty-three patients with recurrent ( n=30), refractory ( n=20), or high-risk ( n=3) lymphoma were enrolled. The 10 patients with HD and 43 with NHL (median age: 46 years, range: 18-64) received busulfan (16 mg/kg), cyclophosphamide (120 mg/kg), and etoposide (30 or 45 mg/kg) followed by ASCT. A total of 50 patients (94%) were consolidated in complete ( n=25) or partial ( n=25) remission, whereas 3 patients had chemoresistant disease before Bu/Cy/VP-16. Thirty-five patients (66%) had received prior radiotherapy (RT) excluding total body irradiation (TBI) as part of the conditioning regimen. The main nonhematological toxicities (grade II-IV according to the Bearman score) in 52 evaluable patients were mucositis (79%) and hepatic toxicity (15%). Severe veno-occlusive disease (VOD) occurred in three patients (5.8%) including one treatment-related death caused by VOD. Overall, treatment-related mortality was 3.8%. After a median follow-up for surviving patients of 21 months (range: 6-118), 20 patients (38%) are in continuous complete remission, 8 patients (15%) are alive in relapse, and 25 patients (47%) died. Probabilities of relapse, event-free survival, and overall survival at 3 years were 63% [95% confidence interval (CI): 48-79%], 31% (95% CI: 17-46%), and 43% (95% CI: 27-59%), respectively. In conclusion, Bu/Cy/VP-16 is an effective and well-tolerated conditioning regimen in patients with HD and NHL. Both toxicity and outcome were not significantly different in patients treated with 30 mg/kg and 45 mg/kg etoposide, respectively. The observed long-term results are even comparable to those published for other established high-dose protocols, including TBI-based regimens. However, further investigations are necessary to evaluate the value of Bu/Cy/VP-16 as a high-dose protocol for malignant lymphoma, especially in patients who have already received extensive RT.

Adolescent↗
PubMed2002

Cooperative action of ADMP- and BMP-mediated pathways in regulating cell fates in the zebrafish gastrula.

It was shown in Xenopus and chick that Spemann's organizer activity is regulated through the negative action of Anti-Dorsalizing Morphogenetic Protein (ADMP). We report the characterization and functional properties of admp in zebrafish. admp expression profile is consistent with a role in the organizer, including the tail organizer. We studied admp function through overexpression experiments, with the use of a dominant-negative form (TR-ADMP) and of an antisense morpholino-modified oligonucleotide. Our results indicate that the ADMP pathway causes the restriction of anterior and axial fates and that ADMP, BMP2b, and BMP7 pathways have distinct actions but cooperate in establishing proper dorso-ventral regionalization. This is shown by partial rescue of the dorsalized mutant snailhouse and of the ventralized mutant chordino, upon admp and tr-admp RNA injection, respectively. Moreover, ADMP and BMP7 probably form heterodimers as shown by the ability of TR-ADMP and BMP7 to antagonize each other. We observed that a MYC-tagged ADMP was secreted and detected in the extracellular space, suggesting that admp could act at a distance. Simultaneous local inhibition of bmp function at the blastoderm margin and impairment of ADMP secretion led to the induction of secondary head structures, confirming that the two pathways cooperatively regulate organizer formation and activity.

Amino Acid Sequence↗
PubMed2002

Allergologic exploration of germins and germin-like proteins, a new class of plant allergens.

BACKGROUND: Germins and the related germin-like proteins (GLPs) are glycoproteins expressed in many plants in response to biotic and abiotic stress. To test the potential impact of germins and GLPs, recombinant germin from Triticum aestivum (tGermin) and GLPs from Arabidopsis thaliana (tGLP), both produced in transformed tobacco plants, were used. METHODS: Sera from 82 patients with type I allergy to birch, grass or mugwort pollen and/or wheat were tested in immunoblot for IgE binding to tGermin and tGLP, and the IgE reactivity after chemical and enzymatic deglycosylation was analysed. The biological activity of tGermin and tGLP was determined in a histamine release assay and in skin prick testing (SPT). RESULTS: In an immunoblotting assay, 24 out of 82 tested sera (29.26%) from allergic patients showed IgE-binding to tGermin, and 18 of these sera (21.95%) displayed also IgE-binding to tGLP. The deglycosylation experiments indicated that glycan moieties contribute significantly to the IgE-binding of tGermin and tGLP. Both tGermins and tGLP induced specifically histamine release in an in vitro assay as well as in SPT. CONCLUSION: Our in vitro and in vivo findings demonstrate that germin and GLPs are capable to bind IgE most likely via carbohydrate determinants, and represent allergenic molecules.

Adult↗
PubMed2001

Biodiversity and ecosystem functioning: current knowledge and future challenges.

The ecological consequences of biodiversity loss have aroused considerable interest and controversy during the past decade. Major advances have been made in describing the relationship between species diversity and ecosystem processes, in identifying functionally important species, and in revealing underlying mechanisms. There is, however, uncertainty as to how results obtained in recent experiments scale up to landscape and regional levels and generalize across ecosystem types and processes. Larger numbers of species are probably needed to reduce temporal variability in ecosystem processes in changing environments. A major future challenge is to determine how biodiversity dynamics, ecosystem processes, and abiotic factors interact.

Animals↗
PubMed2001

Sensitization of resistant lymphoma cells to irradiation-induced apoptosis by the death ligand TRAIL.

A combination of antitumor approaches acting on different death pathways seems ideal for increasing therapeutic responses, especially when defined resistance mechanisms interfere with individual cellular processes. Apoptosis pathways triggered by ionizing radiation (XRT) and the death ligand TRAIL were analysed in Jurkat lymphoma cells. Both induced the activation of caspase-8, caspase-3, BID and mitochondrial potential loss. TRAIL induced apoptosis required caspase-8, whereas it was not essential for radiation induced apoptosis. The inhibition of mitochondrial damage by Bcl-2 abrogated XRT induced apoptosis and caspase activation, but only marginally attenuated TRAIL induced cell death. The combined treatment with TRAIL and XRT exerted additive apoptotic effects in control cells, whereas highly synergistic effects occurred in cells overexpressing Bcl-2. In addition, a strong effect of TRAIL on radiation induced clonogenic cell death was found. In conclusion, TRAIL seems to be of high potential value for a combination with ionizing radiation in tumor therapy.

Apoptosis↗
PubMed2001

Crystal structure of the Acidaminococcus fermentans 2-hydroxyglutaryl-CoA dehydratase component A.

Acidaminococcus fermentans degrades glutamate via the hydroxyglutarate pathway, which involves the syn-elimination of water from (R)-2-hydroxyglutaryl-CoA in a key reaction of the pathway. This anaerobic process is catalyzed by 2-hydroxyglutaryl-CoA dehydratase, an enzyme with two components (A and D) that reversibly associate during reaction cycles. Component A (CompA), a homodimeric protein of 2x27 kDa, contains a single, bridging [4Fe-4S] cluster and uses the hydrolysis of ATP to deliver an electron to the dehydratase component (CompD), where the electron is used catalytically. The structure of the extremely oxygen-sensitive CompA protein was solved by X-ray crystallography to 3 A resolution. The protein was found to be a member of the actin fold family, revealing a similar architecture and nucleotide-binding site. The key differences between CompA and other members of the actin fold family are: (i) the presence of a cluster binding segment, the "cluster helix"; (ii) the [4Fe-4S] cluster; and (iii) the location of the homodimer interface, which involves the bridging cluster. Possible reaction mechanisms are discussed in light of the close structural similarity to members of the actin-fold family and the functional similarity to the nitrogenase Fe- protein.

Actins↗
PubMed2001

Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo-controlled, double blind clinical trial.

This study assessed the clinical efficacy of a chemically standardized willow bark extract in the treatment of osteoarthritis. Willow bark extract, in a dose corresponding to 240 mg salicin/day, was compared with placebo in a 2-week, double-blind, randomized controlled trial. The primary outcome measure was the pain dimension of the WOMAC Osteoarthritis Index. Secondary outcome measures included the stiffness and physical function dimensions of the WOMAC, daily visual analogue scales (VAS) on pain and physical function, and final overall assessments by both patients and investigators. A total of 78 patients (39 willow bark extract, 39 placebo) participated in the trial. A statistically significant difference between the active treatment and the placebo group was observed in the WOMAC pain dimension (d = 6.5 mm, 95% C.I. = 0.2-12.7 mm, p = 0.047); the WOMAC pain score was reduced by 14% from the baseline level after 2 weeks of active treatment, compared with an increase of 2% in the placebo group. The patient diary VAS confirmed this result, and likewise the final overall assessments showed superiority of the willow bark extract over the placebo (patients' assessment, p = 0.0002; investigators' assessment, p = 0.0073). It is concluded that the willow bark extract showed a moderate analgesic effect in osteoarthritis and appeared to be well tolerated.

Adult↗
PubMed2001

Pharmacokinetics of salicin after oral administration of a standardised willow bark extract.

OBJECTIVE: To evaluate the pharmacokinetics of salicin and its major metabolites in humans after oral administration of a chemically standardised willow bark extract. METHODS: Willow bark extract corresponding to 240 mg salicin (1,360 mg, 838 micromol) was ingested by ten healthy volunteers in two equal doses at times 0 h and 3 h. Over a period of 24 h, urine and serum levels of salicylic acid and its metabolites, i.e. gentisic acid and salicyluric acid, were determined using reverse-phase high-performance liquid chromatography. Renal excretion rate, elimination half-life and total bioavailability of salicylates were calculated. RESULTS: Salicylic acid was the major metabolite of salicin detected in the serum (86% of total salicylates), besides salicyluric acid (10%) and gentisic acid (4%). Peak levels were reached within less than 2 h after oral administration. Renal elimination occurred predominantly in the form of salicyluric acid. Peak serum levels of salicylic acid were on average 1.2 mg/l, and the observed area under the serum concentration time curve (AUC) of salicylic acid was equivalent to that expected from an intake of 87 mg acetylsalicylic acid. CONCLUSION: Willow bark extract in the current therapeutic dose leads to much lower serum salicylate levels than observed after analgesic doses of synthetic salicylates. The formation of salicylic acid alone is therefore unlikely to explain analgesic or anti-rheumatic effects of willow bark.

Administration, Oral↗
PubMed2001

Pharmacokinetics of the R- and S-enantiomers of oxybutynin and N-desethyloxybutynin following oral and transdermal administration of the racemate in healthy volunteers.

PURPOSE: To characterize the enantiomers of oxybutynin (OXY) and N-desethyloxybutynin (DEO) following transdermal and oral administration. METHODS: OXY was administered either as a single transdermal system over a 96 h wear period or as a single 5 mg immediate-release tablet to 18 healthy male and female subjects in a randomized, open-label, two-way crossover design. Blood samples were collected for 108 h after application of the transdermal system and for 6 h after oral administration. Plasma concentrations of the R- and S-enantiomers of OXY and DEO were assayed by LC-MS/MS. Enantiomer in vitro skin flux was evaluated using human cadaver skin. RESULTS: In vitro skin flux studies demonstrated equal absorption of R and S- OXY. Plasma concentrations and pharmacokinetic parameters of the R-enantiomers of OXY and DEO were slightly lower than the S-enantiomers following transdermal OXY. The relative AUC values were S-OXY>S-DEO>R-OXY>R-DEO. The AUC ratios of DEO/ OXY were less than 1 for both the R- and S- enantiomers. Following oral dosing, plasma DEO concentrations greatly exceeded OXY resulting in relative AUC values of R-DEO>S-DEO>S-OXY>R-OXY. The mean AUC ratios of S- and R-DEO/OXY were 3.25 and 8.93, respectively. CONCLUSIONS: Stereoselective metabolism of OXY was evident following both transdermal and oral administration of OXY. The reduced pre-systemic metabolism of transdermally administered OXY compared to oral administration resulted in not only significantly lower DEO plasma concentrations, but also a different metabolite pattern. The differences between R-OXY and R-DEO following the two routes of administration support the potential for comparable clinical efficacy and reduced anticholinergic side-effects with transdermal treatment.

Administration, Cutaneous↗
PubMed2001

Transcriptional regulation of oxytocin receptor by interleukin-1beta and interleukin-6.

The up-regulation of oxytocin (OT) receptors in late pregnancy results principally from increased synthesis of messenger RNA. The 5'-flanking region of the human OT receptor gene contains several putative binding sites for nuclear factor-interleukin-6 (NF-IL6), also known as CAAT/enhancer binding protein-beta. This trans-acting factor modulates the expression of genes involved in acute inflammatory responses. Proinflammatory cytokines, such as IL-1beta or IL-6, have been implicated as mediators in both preterm and term labor, particularly in association with intrauterine infection. We hypothesized that IL-1beta and IL-6 induce OT receptor gene expression in human myometrial cells, and this is mediated by NF-IL6 and cognate response elements in the 5'-flanking region of the OT receptor gene. Contrary to the hypothesis, both IL-1beta and IL-6 treatment resulted in a significant decrease in OT receptor messenger RNA measured by ribonuclease protection analysis. Using electrophoretic mobility shift assay, we have shown that NF-IL6 is present at low levels that appear to be increased after treatment with either IL-1beta or IL-6. Using deletion analysis and functional transfection studies in HeLa cells, we demonstrated that the OT receptor gene promoter displays constitutive basal activity and is negatively regulated by both IL-1beta and IL-6. This suppressive ability of IL-1beta and IL-6 depends on the -1203/-722 region of the OT receptor promoter, which contains binding sites for NF-IL6, acute phase response element, and NF-kappaB. Our findings suggest a role for IL-1beta and IL-6 in the transcriptional regulation of the human OT receptor gene.

5' Untranslated Regions↗
PubMed2001

[Marginal fit of dental restorations and the periodontium in Swiss army recruits].

The present study analyzed the relationship between periodontal health adjacent to filled and unfilled tooth sites in young men (recruits). The status of oral health of 419 Swiss army recruits, aged 19 to 20 years was assessed by determining Plaque Index (PI), Retention Index (RI) and Gingival Index (GI) as well as Pocket Probing Depth (PPD) and Probing Attachment Loss (PAL). In addition, the level of alveolar bone was measured using digitized bite-wing radiographs with an enlargement of 4.5x. Filling margins were assessed and the distance between the alveolar bone crest and the cemento-enamel junction (CEJ) measured to the nearest one tenth of a millimeter. These data were compared with the clinical parameters. A total of 8'050 sites were examined. 765 or 9.5 of the sites in the posterior area were filled. 119 of them showed filling overhangs larger than 0.2 mm. Thus, 1.5 % of the examined sites had a significant overhanging margin. All clinical parameters had greater values at filled than at unfilled sites. The differences were statistically not significant. Even the sites with margins overhanging more than 0.8 mm (n=14) did not show significantly different parameters compared to unfilled sites. The comparison with a similar study involving recruits 11 years earlier assessed that the recruits of 1996 had less and smaller filling overhangs. This, in turn, means that, in Switzerland restorative dentistry in young males has been markedly improved during the 1980's and 1990's.

Adult↗
PubMed2000

Genetic analysis of melanophore development in zebrafish embryos.

Vertebrate pigment cells are derived from neural crest, a tissue that also forms most of the peripheral nervous system and a variety of ectomesenchymal cell types. Formation of pigment cells from multipotential neural crest cells involves a number of common developmental processes. Pigment cells must be specified; their migration, proliferation, and survival must be controlled and they must differentiate to the final pigment cell type. We previously reported a large set of embryonic mutations that affect pigment cell development from neural crest (R. N. Kelsh et al., 1996, Development 123, 369-389). Based on distinctions in pigment cell appearance between mutants, we proposed hypotheses as to the process of pigment cell development affected by each mutation. Here we describe the cloning and expression of an early zebrafish melanoblast marker, dopachrome tautomerase. We used this marker to test predictions about melanoblast number and pattern in mutant embryos, including embryos homozygous for mutations in the colourless, sparse, touchdown, sunbleached, punkt, blurred, fade out, weiss, sandy, and albino genes. We showed that in homozygous mutants for all loci except colourless and sparse, melanoblast number and pattern are normal. colourless mutants have a pronounced decrease in melanoblast cell number from the earliest stages and also show poor melanoblast differentiation and migration. Although sparse mutants show normal numbers of melanoblasts initially, their number is reduced later. Furthermore, their distribution indicates a defect in melanoblast dispersal. These observations permit us to refine our model of the genetic control of melanophore development in zebrafish embryos.

Amino Acid Sequence↗
PubMed2000

[Effectiveness and tolerance of standardized willow bark extract in arthrosis patients. Randomized, placebo controlled double-blind study].

OBJECTIVE: To assess the clinical efficacy of a chemically standardized willow bark extract in the treatment of osteoarthritis. METHODS: Willow bark extract, in a dose corresponding to 240 mg salicin/day, was compared to placebo in a 2-week, double-blind, randomized controlled trial. The primary outcome measure was the pain dimension of the WOMAC Osteoarthritis Index. Secondary outcome measures included the stiffness and physical function dimensions of the WOMAC, daily visual analogue scales (VAS) on pain and physical function, and final overall assessment by both patients and investigators. RESULTS: 78 patients (39 willow bark extract, 39 placebo) participated in the trial. A statistically significant difference between active treatment and placebo group was observed in the WOMAC pain dimension (d = 6.5 mm, 95% C.I. = 0.2-12.7 mm, p = 0.047); the WOMAC pain score was reduced by 14% from baseline level after two weeks of active treatment, compared to an increase of 2% in the placebo group. Patient diary VAS confirmed this result, and likewise the final overall assessments showed superiority of willow bark extract over placebo (patients assessment, p = 0.0002; investigators assessment, p = 0.0073). CONCLUSION: Willow bark extract shows a moderate analgesic effect in osteoarthritis.

Activities of Daily Living↗
PubMed2000

Nitroglycerin application during cesarean delivery: plasma levels, fetal/maternal ratio of nitroglycerin, and effects in newborns.

OBJECTIVE: We sought to investigate maternal and fetal nitroglycerin metabolization and to assess the clinical condition of neonates after intravenous nitroglycerin application during cesarean delivery. STUDY DESIGN: At the time of the uterine puncture incision, either 0. 25 mg or 0.5 mg nitroglycerin or a physiologic sodium chloride solution was administered as an intravenous bolus. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and in umbilical blood samples taken immediately after cord clamping. Arterial blood pressure, pulse rates, and Apgar scores were recorded for the neonates 1, 5, and 10 minutes after birth. RESULTS: Sixty-two patients were included in the pharmacokinetic study. Median maternal plasma levels 1 and 5 minutes after injection of 0.5 mg nitroglycerin were 80 and 3.2 ng/mL, respectively; median maternal plasma levels 1 and 5 minutes after injection of 0.25 mg nitroglycerin were 38 and 1.2 ng/mL, respectively. In the umbilical vein 1 minute after application of 0. 5 mg or 0.25 mg nitroglycerin, the plasma levels were 0.41 and 0.09 ng/mL, respectively, and in the umbilical artery they were 0.03 and 0.008 ng/mL, respectively. Circulatory parameters and Apgar scores in the neonates did not differ significantly from those found in the placebo group. CONCLUSION: The level of nitroglycerin in umbilical plasma was two to three orders of magnitude lower than that found in maternal plasma and clearly in a subtherapeutic range. There was no indication that prenatal application of nitroglycerin to facilitate obstetric management is hazardous for neonates.

Adolescent↗
PubMed2000

Equivalent genetic roles for bmp7/snailhouse and bmp2b/swirl in dorsoventral pattern formation.

A bone morphogenetic protein (BMP) signaling pathway acts in the establishment of the dorsoventral axis of the vertebrate embryo. Here we demonstrate the genetic requirement for two different Bmp ligand subclass genes for dorsoventral pattern formation of the zebrafish embryo. From the relative efficiencies observed in Bmp ligand rescue experiments, conserved chromosomal synteny, and isolation of the zebrafish bmp7 gene, we determined that the strongly dorsalized snailhouse mutant phenotype is caused by a mutation in the bmp7 gene. We show that the original snailhouse allele is a hypomorphic mutation and we identify a snailhouse/bmp7 null mutant. We demonstrate that the snailhouse/bmp7 null mutant phenotype is identical to the presumptive null mutant phenotype of the strongest dorsalized zebrafish mutant swirl/bmp2b, revealing equivalent genetic roles for these two Bmp ligands. Double mutant snailhouse/bmp7; swirl/bmp2b embryos do not exhibit additional or stronger dorsalized phenotypes, indicating that these Bmp ligands do not function redundantly in early embryonic development. Furthermore, overexpression experiments reveal that Bmp2b and Bmp7 synergize in the ventralization of wild-type embryos through a cell-autonomous mechanism, suggesting that Bmp2b/Bmp7 heterodimers may act in vivo to specify ventral cell fates in the zebrafish embryo.

Amino Acid Sequence↗