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Biomedical subjects

R Behrens

Publications and source records attributed to R Behrens.

At least 19 recordsLinked to original sources
PubMed2006

Gemcitabine, oxaliplatin and weekly high-dose 5-FU as 24-h infusion in chemonaive patients with advanced or metastatic pancreatic adenocarcinoma: a multicenter phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).

BACKGROUND: Combinations of gemcitabine-oxaliplatin, gemcitabine-5-fluorouracil (5-FU) and 5-FU-oxaliplatin have synergistic activity and nonoverlapping adverse effect profiles. This trial assessed efficacy and safety of the triple combination gemcitabine-oxaliplatin and infusional 5-FU in patients with locally advanced (n=11) or metastatic (n=32) pancreatic adenocarcinoma. PATIENTS AND METHODS: A total of 43 eligible patients were treated with intravenous infusions of gemcitabine (900 mg/m2 over 30 min), followed by oxaliplatin (65 mg/m2 over 2 h) and 5-FU (1500 mg/m2 over 24 h) on days 1 and 8 of a 21-day cycle. RESULTS: Among all 43 patients, the tumor response rate was 19% [95% confidence interval 7% to 30%]. Nine patients were nonassessable for response because they did not complete the first two cycles of chemotherapy due to rapid disease progression, early death or treatment refusal. One patient was lost to follow-up. Median time to progression and overall survival were 5.7 and 7.5 months. Principal grade III/IV toxic effects were leucopenia in 11 (2%), thrombocytopenia in 13 (2%), nausea in 13 (0%), anorexia 16 (7%) and sensory neuropathy in 18 (0%) of patients. Unexpected cardiotoxicity was observed in this trial. CONCLUSION: Response rates and survival of the three-drug combination compare favorably with single-agent gemcitabine, but do not exceed results for doublets.

Adenocarcinoma↗
PubMed2006

How to type test the coefficient of variation of an indication.

Type tests are common methods to verify whether an instrument is suitable for a specific measuring task or not. In several countries, the type test is legally required and if failed the respective instrument cannot be used for legal measurements and, therefore, will not be bought by many customers. One important quantity is the coefficient of variation of the indication, which shall not exceed a given acceptance limit. In order to keep the amount of required measurements manageable, the coefficient of variation is estimated at one or a few test conditions from a limited number of measurements. The current test procedure requires that the measured coefficients of variation shall not exceed the respective acceptance limit at all test conditions. This paper demonstrates that the current test procedure has the unwanted tendency to reject instruments which should pass the test. Based on this realisation, the authors modified the test procedure to achieve proper results. The changes do not require further measurements, only the data evaluation has been optimised.

Data Interpretation, Statistical↗
PubMed2006

Pharmacokinetics and pharmacodynamic action of budesonide in children with Crohn's disease.

BACKGROUND: Budesonide is effective as initial therapy of mild to moderate Crohn's disease in adults. Superior tolerability to conventional corticosteroids might be attributed to extensive first-pass metabolism of budesonide by cytochrome P450 3A. AIM: To evaluate biotransformation and pharmacodynamic action of budesonide in children. METHODS: Drug disposition and effects on endogenous cortisol were evaluated in 12 children with Crohn's disease (5-15 years) after first intake of 3 mg budesonide (single dose), and again after 1 week of thrice daily dosing (steady-state). The parent drug and cytochrome P450 3A-dependent metabolites were analysed in blood and urine. RESULTS: Pharmacokinetic parameters of budesonide following single-dose administration (e.g. AUC(0-infinity) 7.7+/-5.1 h ng/mL, C(max) 1.8+/-1.2 ng/mL) did not change upon multiple dosing. Overall systemic elimination of budesonide reflected by clearance and half-life was not different between children and adults. After 1 week of treatment reversible adrenal suppression was observed - most pronounced in children aged below 12 years. CONCLUSIONS: Disposition of oral budesonide appears to be similar between children and adults, but the doctor has to be aware of an increased risk for adrenal suppression in paediatric patients.

Administration, Oral↗
PubMed2002

Imported Falciparum malaria in Europe: sentinel surveillance data from the European network on surveillance of imported infectious diseases.

Malaria continues to have a high morbidity rate associated among European travelers. Thorough recording of epidemiological and clinical aspects of imported malaria has been helpful in the detection of new outbreaks and areas of developing drug resistance. Sentinel surveillance of data collected prospectively since 1999 has begun within TropNetEurop, a European network focusing on imported infectious diseases. TropNetEurop appears to cover approximately 10% of all patients with malaria seen in Europe. Reports of 1659 immigrants and European patients with Plasmodium falciparum malaria were analyzed for epidemiological information and data on clinical features. Regional data were quite diverse, reflecting local patterns of immigration and international travel. By far, the most infections were imported from West Africa. Europeans had more clinical complications; consequently, all deaths occurred in this group. Compared with European standards, the mortality rate was low (0.6% in Europeans). Data from TropNetEurop member sites can contribute to our understanding of the epidemiological and clinical findings regarding imported falciparum malaria.

Adolescent↗
PubMed2002

A TLD-based few-channel spectrometer for mixed photon, electron, and ion fields with high fluence rates.

A few-channel spectrometer for mixed photon, electron and ion radiation fields has been developed. It consists of a front layer of an etched-track detector foil for detecting protons and ions, a stack of PMMA with thermoluminescent detectors at different depths for gaining spectral information about electrons, and a stack of metallic filters with increasing cut-off photon energies, interspersed with thermoluminescent detectors for gaining spectral information about photons. From the reading of the TL detectors the spectral fluence of the electrons (400 keV to 9 MeV) and photons (20 keV to 2 MeV) can be determined by an unfolding procedure. The spectrometer can be used in pulsed radiation fields with extremely high momentary values of the fluence rate. Design and calibration of the spectrometer are described.

Electrons↗
PubMed2001

Presynaptic Ca2+-activated K+ channels in glutamatergic hippocampal terminals and their role in spike repolarization and regulation of transmitter release.

Large-conductance Ca(2+)-activated K(+) channels (BK, also called Maxi-K or Slo channels) are widespread in the vertebrate nervous system, but their functional roles in synaptic transmission in the mammalian brain are largely unknown. By combining electrophysiology and immunogold cytochemistry, we demonstrate the existence of functional BK channels in presynaptic terminals in the hippocampus and compare their functional roles in somata and terminals of CA3 pyramidal cells. Double-labeling immunogold analysis with BK channel and glutamate receptor antibodies indicated that BK channels are targeted to the presynaptic membrane facing the synaptic cleft in terminals of Schaffer collaterals in stratum radiatum. Whole-cell, intracellular, and field-potential recordings from CA1 pyramidal cells showed that the presynaptic BK channels are activated by calcium influx and can contribute to repolarization of the presynaptic action potential (AP) and negative feedback control of Ca(2+) influx and transmitter release. This was observed in the presence of 4-aminopyridine (4-AP, 40-100 microm), which broadened the presynaptic compound action potential. In contrast, the presynaptic BK channels did not contribute significantly to regulation of action potentials or transmitter release under basal experimental conditions, i.e., without 4-AP, even at high stimulation frequencies. This is unlike the situation in the parent cell bodies (CA3 pyramidal cells), where BK channels contribute strongly to action potential repolarization. These results indicate that the functional role of BK channels depends on their subcellular localization.

4-Aminopyridine↗
PubMed2001

Mev X rays and photoneutrons from femtosecond laser-produced plasmas.

We demonstrate a novel method to monitor the total angular distribution of the spectrum of hard x-ray emission from a plasma generated with femtosecond laser pulses with an intensity of 5 x 10(18) W/cm2 on a solid target. Measured and calculated angular distributions of x rays show a pronounced anisotropy for MeV photon energies. We complemented the spectral information by demonstrating a (gamma,n) nuclear reaction with a tabletop laser system.

Journal Article↗
PubMed2001

Balloon dilation is preferable to bougienage in children with esophageal atresia.

BACKGROUND AND STUDY AIMS: Esophageal strictures are a common problem after surgical repair in children with esophageal atresia. The traditional procedure in these patients is dilation using bougie dilators, usually controlled fluoroscopically or endoscopically. Nowadays, an alternative technique is balloon-catheter dilation. The aim of this study was to report our experience with pneumatic balloon dilation and to compare this method with previously performed bougienage with regard to efficacy. PATIENTS AND METHODS: Over 16 years, 34 patients who developed symptomatic strictures were encountered at our institution. In the first 9 years 12 patients underwent 178 bougienages (group C). In the last 7 years six patients who had undergone 202 previous bougienages (group B), and 16 patients who had undergone no bougienages (group A), underwent 52 dilations. The dilation was carried out under intravenous sedation using a combination of midazolam and etomidate. The balloon was placed in the stricture endoscopically and the procedure was performed under fluoroscopic and endoscopic control. RESULTS: In all patients the dilation was effective and involved minimal trauma. The strictures required 1 to 7 procedures (median 2) over a maximum of 18 months (median 3 months) for a good treatment result. The complications observed were two perforations, one of them with pneumothorax (both treated conservatively), and two compressions of the trachea (interruption of the procedure, but efficient dilation was eventually achieved). The method was more effective than bougienage (1 to 60 bougienages were required per patient, median 9). CONCLUSIONS: Compared with traditional bougienage, balloon dilation of esophageal strictures is less traumatic and more effective. Complications are rare and can be managed conservatively. In our opinion this procedure is the appropriate treatment for strictures, even in very small infants, after repair of esophageal atresia.

Catheterization↗
PubMed2000

Fission yeast retrotransposon Tf1 integration is targeted to 5' ends of open reading frames.

Target site selection of transposable elements is usually not random but involves some specificity for a DNA sequence or a DNA binding host factor. We have investigated the target site selection of the long terminal repeat-containing retrotransposon Tf1 from the fission yeast Schizosaccharomyces pombe. By monitoring induced transposition events we found that Tf1 integration sites were distributed throughout the genome. Mapping these insertions revealed that Tf1 did not integrate into open reading frames, but occurred preferentially in longer intergenic regions with integration biased towards a region 100-420 bp upstream of the translation start site. Northern blot analysis showed that transcription of genes adjacent to Tf1 insertions was not significantly changed.

Binding Sites↗
PubMed2000

hKCNMB3 and hKCNMB4, cloning and characterization of two members of the large-conductance calcium-activated potassium channel beta subunit family.

We cloned two beta subunits of large-conductance calcium-activated potassium (BK) channels, hKCNMB3 (BKbeta1) and hKCNMB4 (BKbeta4). Profiling mRNA expression showed that hKCNMB3 expression is enriched in testis and hKCNMB4 expression is very prominent in brain. We coexpressed BK channel alpha (BKalpha) and BKbeta4 subunits in vitro in CHO cells. We compared BKalpha/beta4 mediated currents with those of smooth muscle BKalpha/beta1 channels. BKbeta4 slowed activation kinetics more significantly, led to a steeper apparent calcium sensitivity, and shifted the voltage range of BK current activation to more negative potentials than BKbeta1. BKalpha/beta4 channels were not blocked by 100 nM charybdotoxin or iberiotoxin, and were activated by 17beta-estradiol.

Amino Acid Sequence↗
PubMed2000

Pharmacokinetics of orally administered omeprazole in children. International Pediatric Omeprazole Pharmacokinetic Group.

OBJECTIVES: The aim of this study was to examine the pharmacokinetics of orally administered omeprazole in children. METHODS: Plasma concentrations of omeprazole were measured at steady state over a 6-h period after administration of the drug. Patients were a subset of those in a multicenter study to determine the dose, safety, efficacy, and tolerability of omeprazole in the treatment of erosive reflux esophagitis in children. Children were 1-16 yr of age, with erosive esophagitis and pathological acid reflux on 24 h-intraesophageal pH study. The "healing dose" of omeprazole was that at which subsequent intraesophageal pH study normalized. Children remained on this dose for 3 months, and during this period the pharmacokinetics were measured. RESULTS: A total of 57 children were enrolled in the overall healing phase of the study. Pharmacokinetic study was optional for subjects and was performed in 25 of the 57 enrolled. The doses of omeprazole required were substantially higher doses per kilogram of body weight than in adults. Values of the pharmacokinetic parameters of omeprazole were generally within the ranges previously reported in adults. However, the plasma levels, area under the plasma concentration versus time curve (AUC), plasma half-life (t(1/2)), and maximal plasma concentration (Cmax), were lower in the younger age group, when the AUC and Cmax were normalized to a dose of 1 mg/kg. Furthermore, within the group as a whole, these values showed a gradation from lowest in the children 1-6 yr of age to higher in the older age groups. CONCLUSIONS: The pharmacokinetics of omeprazole in children showed a trend toward higher metabolic capacity with decreasing age, being highest at 1-6 yr of age. This may explain the need for higher doses of omeprazole on a per kilogram basis, not only in children overall compared with adults but, in many cases, particularly in younger children.

Administration, Oral↗
PubMed1999

Late manifestation of Indian childhood cirrhosis in a 3-year-old German girl.

UNLABELLED: We report on a 3.8-year-old German girl who presented with signs of subacute liver failure based on a 4-month history. Investigations done before admission excluded infectious, metabolic and immunological diseases. Laboratory findings were increased values of aminotransferases, hyperbilirubinaemia, hyperammonaemia and deteriorated plasmatic coagulation. Caeruloplasmin and serum copper concentrations were normal; however, urinary copper excretion was elevated (80 microg/l). Liver biopsy showed a micronodular liver cirrhosis and an extremely high liver copper concentration (1400 microg/g dry weight). Epidemiological investigations revealed an elevated copper concentration (8645 microg/l, normal: <2000) and a low pH value (6.3) of the drinking water supplied by copper pipes. The girl had been exposed to copper-contaminated drinking water since the age of 2 years. CONCLUSION: Laboratory, histopathological findings and a proven chronic copper intoxication lead to the diagnosis of Indian childhood cirrhosis in a German girl. Whereas this disease is mostly described in patients with increased copper intake in infancy, our patient developed toxic liver cirrhosis with relatively late copper exposure. Indian childhood cirrhosis should be considered in the differential diagnosis of early childhood liver cirrhosis.

Child, Preschool↗
PubMed1999

Dual versus triple therapy of Helicobacter pylori infection: results of a multicentre trial.

OBJECTIVE: To compare dual therapy (omeprazole and amoxicillin) with triple therapy (omeprazole, amoxicillin, and clarithromycin) in the treatment of Helicobacter pylori infection. The efficacy of 1 mg/kg/day omeprazole was randomly compared with 2 mg/kg/day. STUDY DESIGN: 252 patients (median age, 11.0 years; range, 3-18) presenting with chronic abdominal pain underwent endoscopy and a 13C-urea breath test. Gastric biopsy specimens were taken for histological examination and for the rapid urease test. Patients were treated for two weeks: group A (n = 63) received amoxicillin (50 mg/kg; maximum, 2 g/day), group B (n = 73) received amoxicillin and clarithromycin (20 mg/kg; maximum, 1 g/day). Both groups were randomly treated with either 1 or 2 mg/kg omeprazole (maximum, 80 mg/day). Diagnostic procedures were repeated four weeks after the end of treatment. RESULTS: 11 patients were excluded; 136 patients were H pylori positive (56%), 105 of whom were re-examined after treatment. Helicobacter pylori was eradicated in 52% of group A and 83% of group B. The dose of omeprazole had no influence on the eradication rate. Specificity and sensitivity of the rapid urease test were 94% and 93%, respectively. Specificity and sensitivity of the 13C-urea breath test were 93% and 95%, respectively. CONCLUSIONS: Dual therapy can no longer be recommended. Triple therapy is more effective than dual therapy in the eradication of H pylori infection. The lower dose of 1 mg/kg omeprazole was as effective as 2 mg/kg.

Adolescent↗
PubMed1999

Another case of achalasia-microcephaly syndrome.

The first German patient with achalasia-microcephaly syndrome is described. The mother was exposed to the anti-malarial drug Mefloquine during the first 8 weeks of pregnancy.

Abnormalities, Drug-Induced↗
PubMed1998

[Eosinophil cationic protein in a 39-year-old patient with Churg-Strauss syndrome].

HISTORY AND CLINICAL FINDINGS: A 39-year-old woman in good health suddenly developed painful paraesthesia and incomplete paresis of all four limbs. Furthermore, arterial hypertension and tachycardia were found. The patient reported a history of chronic allergic rhinitis for 10 years and asthma one year. INVESTIGATIONS: Laboratory data showed an increased leucocyte count with a substantial increase in eosinophils in peripheral blood as well as in bone marrow. Nonspecific inflammatory markers such as erythrocyte sedimentation rate, C-reactive protein, fibrinogen as well as eosinophil cationic protein (ECP) were also increased. Histological investigations of a skin-muscle biopsy of the quadriceps revealed necrotizing vasculitis with extravascular granulomata and histiocytic giant cells. DIAGNOSIS, TREATMENT AND COURSE: Based on the diagnosis of Churg-Strauss syndrome treatment with methylprednisolone (500 mg every second day) was started, but was found to be ineffective after 10 days. Symptoms responded well to a subsequent course of 150 mg cyclophosphamide combined with 50 mg prednisolone per day. Pareses and pain were significantly reduced and all qualitative nerve functions returned to normal within two weeks of treatment. Laboratory parameters, especially the ECP, were similarly normalized. CONCLUSION: Churg-Strauss syndrome should be considered in the differential diagnosis of unexplained polyneuropathy. Determination of ECP may not only help in the diagnosis but does also facilitate monitoring of treatment and of further course of the disease.

Adult↗