Biomedical subjects

H Schmidt

Publications and source records attributed to H Schmidt.

At least 19 recordsLinked to original sources

PubMed2007

[Clinical experience with the hygienic reprocessing of rigid endoscopes lacking a working channel with reference to practicability in clinical routine].

BACKGROUND: Contaminated medical products may be vectors for infections. A safe disinfection method for the optical instruments used by ENT specialists is undoubtedly needed. So far, a standard method that sufficiently covers the risk of infection for patients and medical staff alike, while serving the need of practicability in daily routine, has not been established. PATIENTS AND METHODS: In the ENT departments of the Mannheim and Kaiserslautern hospitals, a study on the practicability of disinfection rigid optical instruments lacking working channels was conducted using cleaning and disinfection automats. A total of 735 patients were examined (Hopkins 30 degrees and 70 degrees) and the endoscopes subsequently sterilized using a cleaning and disinfection automat. RESULTS: Each cleaning cycle took about 40 min. Examining 70-100 patients a day, a minimum of eight 70 degrees Hopkins endoscopes would be needed. CONCLUSION: The sterilization of medical products such as endoscopes is the best practice, but certain hindrances, such as loss of time and costs involved, complicate its general application.

Endoscopes, Gastrointestinal↗

PubMed2007

The partial 5-hydroxytryptamine1A receptor agonist buspirone does not antagonize morphine-induced respiratory depression in humans.

Based on experiments in rats, serotonin receptor 5-hydroxytryptamine (5-HT)(1A) agonists have been proposed as a potential therapeutic strategy for the selective treatment of opioid-induced respiratory depression. We investigated the clinical applicability of this principle in healthy volunteers. Twelve subjects received 0.43 mg/kg morphine (30 mg for 70 kg body weight) administered intravenously (i.v.) over approximately 2 h. At the start of the morphine infusion, they received in a randomized, double-blind cross-over design 60 mg p.o. buspirone or placebo. Respiratory depression (hypercapnic challenge) and pain (electrical stimuli: 5 Hz sinus 0-20 mA; chemical stimuli: 200 ms gaseous CO(2) pulses applied to the nasal mucosa) were assessed at baseline, at the end of the morphine infusion, and a third time after antagonizing the opioid effects by i.v. administration of 2 mg naloxone. The linear relationship between the minute ventilation and the CO(2) concentration in the inspired air of 1.07+/-0.27 l/mm Hg CO(2) at baseline conditions became shallower (0.45+/-0.23 l/mm Hg CO(2)) after morphine administration (P<0.001), indicating respiratory depression, which was significantly reversed by naloxone (0.95+/-0.43 l/mm Hg CO(2); P=0.001). Co-administration of buspirone had no effect on morphine-induced respiratory depression (slope 0.45+/-0.23 l/mm Hg CO(2) under morphine plus placebo versus 0.38+/-0.25 l/mm Hg CO(2) under morphine plus buspirone; P=0.7). Significant morphine-induced analgesia was observed in both pain models and was reversed by naloxone but unaffected by buspirone. Buspirone significantly increased the nausea induced by morphine (P=0.011). Oral co-administration of a high dose of the clinically available 5-HT(1A) agonist buspirone cannot be advised as a remedy for opioid-induced respiratory depression. This is indicated by its lack of anti-respiratory depressive effects and by the buspirone-associated increase of morphine-induced nausea.

Adult↗

PubMed2006

Clinical and anti-inflammatory effects of treating endotoxin-challenged pigs with meloxicam.

The clinical and anti-inflammatory effects of a single treatment of 0.4 mg meloxicam/kg bodyweight on pigs that had been challenged with Escherichia coli endotoxin were investigated. Significantly lower total clinical scores were recorded in pigs treated with meloxicam than in pigs treated with a placebo. Significantly higher mean serum concentrations of thromboxane B(2) were also recorded in pigs treated with a placebo for up to 24 hours after the challenge. The serum concentrations of acute phase proteins and specific antibody titres to E coli lipopolysaccharide were unaffected by the meloxicam. The meloxicam treatment was well tolerated.

Acute-Phase Proteins↗

PubMed2006

Expression of the stem cell self-renewal gene Hiwi and risk of tumour-related death in patients with soft-tissue sarcoma.

Self-renewal is considered as a common property of stem cells. Dysregulation of stem cell self-renewal is likely a requirement for the development of cancer. Hiwi, the human Piwi gene, encodes a protein responsible for stem cell self-renewal. In this study, we investigated the expression of Hiwi at the RNA level by real-time quantitative PCR in 65 primary soft-tissue sarcomas (STS) and ascertained its impact on prognosis for STS patients. In a multivariate Cox's proportional hazards regression model, we found that an increased expression of Hiwi mRNA is a significant negative prognostic factor for patients with STS (P=0.017; relative risk 4.6, 95% confidence interval (CI) 1.3-16.1) compared to medium expression of Hiwi transcript. However, a low expression of Hiwi transcript is correlated with a 2.4-fold (CI 0.7-8.0) increased risk, but this effect was not significant (P=0.17). Altogether, high-level expression of Hiwi mRNA identifies STS patients at high risk of tumour-related death. This is the first report showing a correlation between expression of a gene involved in stem cell self-renewal and prognosis of cancer patients.

Adult↗

PubMed2006

Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplication.

Codeine is an analgesic drug acting on mu-opiate receptors predominantly via its metabolite morphine, which is formed almost exclusively by the genetically polymorphic enzyme cytochrome P450 2D6 (CYP2D6). Whereas it is known that individuals lacking CYP2D6 activity (poor metabolizers, PM) suffer from poor analgesia from codeine, ultra-fast metabolizers (UM) due to the CYP2D6 gene duplication may experience exaggerated and even potentially dangerous opioidergic effects and no systematical study has been performed so far on this question. A single dose of 30 mg codeine was administered to 12 UM of CYP2D6 substrates carrying a CYP2D6 gene duplication, 11 extensive metabolizers (EM) and three PM. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism methods and a single-base primer extension method for characterization of the gene-duplication alleles. Pharmacokinetics was measured over 24 h after drug intake and codeine and its metabolites in plasma and urine were analyzed by liquid chromatography with tandem mass spectrometry. Significant differences between the EM and UM groups were detected in areas under the plasma concentration versus time curves (AUCs) of morphine with a median (range) AUC of 11 (5-17) microg h l(-1) in EMs and 16 (10-24) microg h l(-1) in UM (P=0.02). In urine collected over 12 h, the metabolic ratios of the codeine+codeine-6-glucuronide divided by the sum of morphine+its glucuronides metabolites were 11 (6-17) in EMs and 9 (6-16) in UM (P=0.05). Ten of the 11 CYP2D6 UMs felt sedation (91%) compared to six (50%) of the 12 EMs (P=0.03). CYP2D6 genotypes predicting ultrarapid metabolism resulted in about 50% higher plasma concentrations of morphine and its glucuronides compared with the EM. No severe adverse effects were seen in the UMs in our study most likely because we used for safety reasons a low dose of only 30 mg. It might be good if physicians would know about the CYP2D6 duplication genotype of their patients before administering codeine.

Administration, Oral↗

PubMed2006

APOE epsilon variation in multiple sclerosis susceptibility and disease severity: some answers.

BACKGROUND: Previous studies have examined the role of APOE variation in multiple sclerosis (MS), but have lacked the statistical power to detect modest genetic influences on risk and disease severity. The meta- and pooled analyses presented here utilize the largest collection, to date, of MS cases, controls, and families genotyped for the APOE epsilon polymorphism. METHODS: Studies of MS and APOE were identified by searches of PubMed, Biosis, Web of Science, Cochrane Review, and Embase. When possible, authors were contacted for individual genotype data. Meta-analyses of MS case-control data and family-based analyses were performed to assess the association of APOE epsilon genotype with disease risk. Pooled analyses of MS cases were also performed to assess the influence of APOE epsilon genotype on disease severity. RESULTS: A total of 22 studies (3,299 MS cases and 2,532 controls) were available for meta-analysis. No effect of epsilon2 or epsilon4 status on MS risk was observed (summary OR 1.14, 95% CI 0.96-1.34 and OR 0.89, 95% CI 0.78-1.01). Results obtained from analyses of APOE genotypes in 1,279 MS families were also negative (p = 0.61). Finally, results from pooled analyses of 4,048 MS cases also argue strongly that APOE epsilon status does not distinguish a relapsing-remitting from primary progressive disease course, or influence disease severity, as measured by the Expanded Disability Status Scale and disease duration. CONCLUSION: Overall, these findings do not support a role for APOE in multiple sclerosis, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype-phenotype relationships.

Alleles↗

PubMed2006

Cyclopamine increases the cytotoxic effects of paclitaxel and radiation but not cisplatin and gemcitabine in Hedgehog expressing pancreatic cancer cells.

INTRODUCTION: The hedgehog signaling pathway (Hh) is frequently over expressed in pancreatic adenocarcinomas. We studied the potential cytotoxic interactions between cyclopamine, a Hh pathway inhibitor and paclitaxel, cisplatin, gemcitabine and ionizing radiation (IR). METHODS: In vitro clonogenic survival analysis was performed with cyclopamine alone or cyclopamine in combination with paclitaxel, gemcitabine, cisplatin and IR in Hh expressing human pancreatic tumor cells and Hh non-expressing colon cancer cells. Relative cytotoxicity was assessed in combination treatment compared with exposure to single agents. Assays of apoptosis (annexin V) were performed in the presence of cyclopamine, chemotherapeutic agents, and IR. RESULTS: We report that cyclopamine increased the cytotoxic effects of paclitaxel and IR in Hh expressing pancreatic carcinoma cells. These effects were not observed in Hh non-expressing cells. Cyclopamine did not significantly increase killing by cisplatin or gemcitabine in Hh expressing pancreatic cancer cells. CONCLUSIONS: These data suggest strategies to combine Hh inhibitors with radiotherapy and chemotherapeutic agents, specifically paclitaxel and related compounds in the treatment of pancreatic cancer.

Antineoplastic Agents↗

PubMed2006

Nitrogen diffusion in amorphous silicon nitride isotope multilayers probed by neutron reflectometry.

Amorphous silicon nitride is a model system for a covalently bound amorphous solid with a low atomic mobility where reasonable values of self-diffusivities are still lacking. We used neutron reflectometry on isotope enriched Si3 14N4/Si3 15N4 multilayers to determine nitrogen self-diffusivities ranging from 10(-24) to 10(-21) m2/s between 950 and 1250 degrees C. Time dependent diffusivities observed at 1150 degrees C indicate the presence of structural relaxation. For long annealing times (relaxed state) the diffusivities follow an Arrhenius law with an activation enthalpy of (3.6 +/- 0.4) eV. The results are indicative of a direct diffusion mechanism without the involvement of thermal point defects.

Journal Article↗

PubMed2006

Lack of association of lobar intracerebral hemorrhage with apolipoprotein E genotype in an unselected population.

BACKGROUND: Both the upsilon2 and upsilon4 alleles of the apolipoprotein E gene (APOE) have been reported to be overrepresented in lobar intracerebral hemorrhage and to be associated with cerebral amyloid angiopathy (CAA). These studies were performed primarily on the North American population and investigated in partly selected patient cohorts. METHODS: 193 consecutive patients suffering from primary intracerebral hemorrhage (ICH) were included in our study. The localization of the ICH, i.e. cortico-subcortical, deep white matter, basal ganglia, brainstem and cerebellum, was put in relation to the APOE genotype and vascular risk factors. In 101 of these patients, the APOE genotype was also correlated to the presence and distribution of microbleeds and other microangiopathy-related damage, as shown by magnetic resonance imaging (MRI). RESULTS: We found neither an association of a specific APOE genotype with ICH localization nor with microangiopathy-related MRI findings. CONCLUSIONS: In our study of an unselected Central European population, the APOE genotype was not confirmed as a candidate for providing additional diagnostic and potentially prognostic information in patients with ICH.

Aged↗

PubMed2006

Atrial fibrillation - patients at high risk for cerebral embolism.

OBJECTIVE: Patients with atrial fibrillation (AF) have a risk of cerebral embolism. Echocardiographic parameters elevate this risk significantly. However, there is little knowledge about the long-term fate and the rate of clinically silent cerebral embolism under continued oral anticoagulation. The aims of our study were to assess prognosis of patients with AF and determine a high risk group with an increased risk of cerebral embolism under oral anticoagulation. METHODS: Consecutive patients with persistent or permanent AF and left atrial (LA) thrombi, dense spontaneous echo contrast (SEC) and/or reduced LA appendage peak emptying velocities (LAAv) were included in the study (N = 128). Patients with AF and without echocardiographic risk factors (N = 114) served as controls. All patients were examined with transesophageal echocardiography, cranial magnetic resonance imaging and clinically during a period of three years. RESULTS: During the three-year follow-up period 6 (5%) of the high risk patients had cerebral embolism with neurological deficits. 4 (3%) patients died due to embolic events and 17 (13%) patients had silent embolism as documented on MRI. In the control group 8 (7%) patients had embolic events (n = 1 clinically apparent and n = 7 silent embolism) documented on MRI, one was clinically apparent. Study patients with an event had more commonly previous thromboembolism (p < 0.0001). CONCLUSIONS: Patients with peristent or permanent AF and LA thrombi, dense SEC or reduced LAAv have an explicitly increased risk of cerebral embolism (21%) despite oral anticoagulation. Previous thromboembolic event is another important predictor for an event.

Atrial Fibrillation↗

PubMed2006

[Therapy for sleep-related breathing disorders using positive airway pressure. Data from an HNO sleep laboratory].

BACKGROUND: Computer-assisted cardiopulmonary polysomnography is generally required to differentiate common snoring from serious sleep-related breathing disorders (SRBD) such as sleep apnea. METHODS: This study investigates data from 2,683 diagnostic and therapeutic cardiopulmonary polysomnographies of 1,087 patients over the period 2003-2004. Indications and efficacy of therapy using positive airway pressure (PAP) in SRBD are analyzed as well as alternative procedures. RESULTS: Of the 1,087 patients, 260 (23.9%) needed PAP therapy. In 61% of the patients CPAP-therapy was applied, 19% needed Bi-PAP-ST and 10% Bi-PAP-S-therapy. A total of 91 patients (8.4%) were treated with alternative procedures, partially combined with positive airway pressure. In 760 patients (69.9%) PAP-therapy was controlled or SRBD was excluded. CONCLUSION: There are no generally accepted guidelines for the therapy of SRBD. Indications for conservative and/or surgical procedures in the treatment have to be determined individually, depending on polysomnographic findings, subjective discomfort and physical comorbidities of the patients.

Adolescent↗

PubMed2006

Tissue distribution of cefquinome after intramammary and "systemic" administration in the isolated perfused bovine udder.

Mammary glands taken at slaughter from healthy lactating cows were perfused in vitro with warmed and gassed Tyrode solution. Cefquinome (88.8mg cefquinome sulphate per 8mL) was administered by the intramammary route to all quarters and/or "systemically" via the perfusion fluid at concentrations similar to those measured in plasma following intramuscular administration of 1mg cefquinome per kg body weight. Samples of the perfusate were taken over a 6-h period and from the regional lymph nodes after 6h. Using a scalpel, sections of glandular tissue - at different distances from and vertical to the teat right up to the udder base - were gathered from four quarters each per route of administration at 2, 4 and 6h. The cefquinome content of the tissue samples was analysed by high performance liquid chromatography with diode array detection and of the perfusate samples by bioassay. After intramammary administration, the concentration of cefquinome in the glandular tissue decreased exponentially with increasing distance from the teat. The addition of cefquinome to the perfusion fluid produced a mean concentration of 0.2-0.5microg/g at all glandular tissue sites. Combined intramammary and systemic treatment ensured that concentrations exceeded the MIC(90) values of the most common mastitis pathogens in all areas of the udder by 2h post-administration. There was considerable variability in the tissue concentrations of cefquinome, particularly after intramammary administration. These results suggest that for the treatment of acute mastitis a combination of both intramammary and systemic administration is likely to be advantageous in order to rapidly produce maximum cefquinome concentrations in all regions of the udder.

Animals↗

PubMed2006

Deterministic modelling and stochastic simulation of biochemical pathways using MATLAB.

The analysis of complex biochemical networks is conducted in two popular conceptual frameworks for modelling. The deterministic approach requires the solution of ordinary differential equations (ODEs, reaction rate equations) with concentrations as continuous state variables. The stochastic approach involves the simulation of differential-difference equations (chemical master equations, CMEs) with probabilities as variables. This is to generate counts of molecules for chemical species as realisations of random variables drawn from the probability distribution described by the CMEs. Although there are numerous tools available, many of them free, the modelling and simulation environment MATLAB is widely used in the physical and engineering sciences. We describe a collection of MATLAB functions to construct and solve ODEs for deterministic simulation and to implement realisations of CMEs for stochastic simulation using advanced MATLAB coding (Release 14). The program was successfully applied to pathway models from the literature for both cases. The results were compared to implementations using alternative tools for dynamic modelling and simulation of biochemical networks. The aim is to provide a concise set of MATLAB functions that encourage the experimentation with systems biology models. All the script files are available from www.sbi.uni-rostock.de/ publications_matlab-paper.html.

Biochemistry↗

PubMed2006

Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience.

Acute hepatitis B progresses to liver failure with the need of liver transplantation in about 1% of cases. We treated patients with severe acute or fulminant hepatitis B with lamivudine in an attempt to prevent hepatitis B virus (HBV) reinfection after potential liver transplantation. Since September 2000, 17 patients with severe acute or fulminant HBV infection were treated with 100 or 150 mg lamivudine daily once we had evidence for a severe course as indicated by an INR >2.0. These were compared to a historic control from our unit and to external patients. Fourteen of the 17 patients (82.4%) survived with full recovery without liver transplantation. All these 14 individuals cleared HBsAg on lamivudine within less than 6 months. Twelve patients recovered quickly as indicated by a normalized prothrombin time within 1 week while two patients had a more prolonged course. None of the patients showed an adverse event. Three patients requiring transplantation despite lamivudine therapy had more advanced disease on admission, of whom one had additionally ingested paracetamol (acetaminophen) while the second was already HBV-DNA negative by polymerase chain reaction on admission. The lamivudine treated patients had significant higher frequency of survival without liver transplantation 82.4 vs 20% (4/20) in the historic control (P < 0.001). Similar data were derived from external centres using lamivudine (15/20, 75%). Lamivudine is safe in patients with severe acute or fulminant hepatitis B, leading to fast recovery with the potential to prevent liver failure and liver transplantation when administered early enough.

Adult↗

PubMed2006

A case of cerebral Whipple's disease initially presenting with isolated focal myoclonus.

Neurological manifestations in Whipple's disease are highly variable and tend to occur at later stages of the disease. However, isolated, focal neurological symptoms are reported to be rare. Here we describe the successful treatment of a case of cerebral Whipple's disease initially presenting solely with isolated myoclonic jerks of the left hand and forearm evolving to a segmental myoclonus at a later stage. Additionally, we present - to our knowledge - a novel treatment by administration of immunomodulatory therapy (IVIg) in addition to established antibiotics.

Adult↗

PubMed2006

Paternal and maternal lineages in the Balkans show a homogeneous landscape over linguistic barriers, except for the isolated Aromuns.

The Balkan Peninsula is a complex cultural mosaic comprising populations speaking languages from several branches of the Indo-European family and Altaic, as well as culturally-defined minorities such as the Aromuns who speak a Romance language. The current cultural and linguistic landscape is a palimpsest in which different peoples have contributed their cultures in a historical succession. We have sought to find any evidence of genetic stratification related to those cultural layers by typing both mtDNA and Y chromosomes, in Albanians, Romanians, Macedonians, Greeks, and five Aromun populations. We have paid special attention to the Aromuns, and sought to test genetically various hypotheses on their origins. MtDNA and Y-chromosome haplogroup frequencies in the Balkans were found to be similar to those elsewhere in Europe. MtDNA sequences and Y-chromosome STR haplotypes revealed decreased variation in some Aromun populations. Variation within Aromun populations was the primary source of genetic differentiation. Y-chromosome haplotypes tended to be shared across Aromuns, but not across non-Aromun populations. These results point to a possible common origin of the Aromuns, with drift acting to differentiate the separate Aromun communities. The homogeneity of Balkan populations prevented testing for the origin of the Aromuns, although a significant Roman contribution can be ruled out.

Chromosomes, Human, Y↗

PubMed2006

Bacterial vaginosis in a cohort of Danish pregnant women: prevalence and relationship with preterm delivery, low birthweight and perinatal infections.

OBJECTIVE: To determine the prevalence of bacterial vaginosis (BV) in the second trimester of pregnancy in a Danish population using the Schmidt criteria and to examine whether BV was associated with subsequent preterm delivery, low birthweight or perinatal infections. DESIGN: Prospective cohort study. SETTING: Department of Obstetrics and Gynaecology at a University Hospital, Denmark. POPULATION: Three thousand five hundred and forty pregnant women aged 18 years or more. METHODS: A smear from the vagina was obtained from all women, air-dried and stored for subsequent diagnosis of BV. After rehydration with isotonic saline, the smear was examined in a phase-contrast microscope at 400x, and the numbers of lactobacilli morphotypes and small bacterial morphotypes were counted. A score for BV was calculated according to the method described by Schmidt. The outcome of pregnancy from 20 weeks of gestation was examined in the 3262 singleton pregnant women who were included in this study before 20 weeks of gestation. The relationship between BV and adverse outcome of pregnancy was examined by univariate and multivariate analyses. MAIN OUTCOME MEASURES: Prevalence of BV, preterm delivery (<37 weeks), low birthweight (<2500 g), preterm delivery of a low-birthweight infant and clinical chorioamnionitis. RESULTS: The prevalence of BV was 16%, and the rate of preterm delivery was 5.2% in the study population of 3262 singleton pregnant women who were included before 20 weeks of gestation. Mean birthweight was significantly lower in infants of women with BV than in infants of women without BV (3408 versus 3511 g, P < 0.01). Univariate analyses showed that BV was marginally associated with preterm delivery but significantly associated with low birthweight, preterm delivery of a low birthweight infant, indicated preterm delivery and clinical chorioamnionitis. Multivariate analyses, which adjusted for previous miscarriage, previous preterm delivery, previous conisation, smoking, gestational diabetes, fetal death and preterm premature rupture of membranes, showed that BV was significantly associated with low birthweight (OR 1.95, 95% CI 1.3-2.9), preterm delivery of a low-birthweight infant (OR 2.5, 95% CI 1.6-3.9), indicated preterm delivery (OR 2.4, 95% CI 1.4-4.1) and clinical chorioamnionitis (OR 2.7, 95% CI 1.4-5.1). CONCLUSIONS: The prevalence of BV determined using the Schmidt criteria in the early second trimester of pregnancy was similar to that found in similar studies. The presence of BV before 20 weeks of gestation was an independent risk factor for delivery of an infant with low birthweight, preterm delivery of a low-birthweight infant, indicated preterm delivery and clinical chorioamnionitis.

Cohort Studies↗

PubMed2006

Sleep disorders are long-term sequelae of both bacterial and viral meningitis.

BACKGROUND: Many bacterial meningitis patients experience neurological or neuropsychological sequelae, predominantly deficits in short-term memory, learning, and attention. Neuropsychological symptoms after viral meningitis are observed less frequently. Sleep disturbance has been reported after both viral and bacterial meningitis. OBJECTIVES: To examine systematically the frequency and extent of sleep disturbance in meningitis patients. METHODS: Eighty six viral or bacterial meningitis (onset of acute disease at least 1 year previously) patients were examined using two standardised questionnaires (Schlaffragebogen B and the Pittsburgh Sleep Quality Index, PSQI) in conjunction with a standardised neurological examination, and compared to a control group of 42 healthy age-matched volunteers. RESULTS: Patients after both viral and bacterial meningitis described their sleep as reduced in quality and less restful than that of healthy control subjects; both patient groups had a pathological mean PSQI total score. Impaired sleep scores after meningitis were not correlated to either the Glasgow Coma Scale or the Glasgow Outcome Scale. Moreover, no relationship between residual neurological dysfunction or depressivity and sleep quality was observed. CONCLUSIONS: Impaired sleep is a long-term consequence of meningitis. Additional, so far undetermined, factors other than the severity of concomitant neurological deficits are responsible for the development of this sequela.

Acute Disease↗