Biomedical subjects

W Müller

Publications and source records attributed to W Müller.

At least 109 records · Page 6Linked to original sources

PubMed2001

Body position-dependent changes in cerebral hemodynamics during apnea in preterm infants.

The objective of the present study was to evaluate sleeping position-dependent effects on cerebral hemodynamics during apnea in preterm infants. To this end, polygraphic studies were performed on 15 stable preterm infants lying prone and lying supine. Changes in cerebral blood volume (DeltaCBV) and in cerebral hemoglobin oxygenation ((Delta)cHbD) in association with apnea were measured by near infrared spectroscopy. For comparison, apnea in the prone position was matched for duration to apnea in the supine position. A total number of 98 pairs of apnea were compared. The mean duration of apnea was 8.2+/-3 s. In both positions there was a predominance of decrease in CBV and cHbD in association with apnea. The mean decrease of cHbD (-1.57+/-1.82 micromol/l) and of CBV (-0.120+/-0.137 ml/100g brain) in the supine position was significantly pronounced compared to prone position (DeltacHbD: -1.18+/-1.77 micromol/l, DeltaCBV: -0.080+/-0.095 ml/100 g brain). The degree of DeltaCBV and DeltaHbD did not correlate with postconceptional or postnatal age (r2<0.01). In both positions there was a similar small decrease of SaO2 in association with apnea. In the supine position heart rate decreased slightly during apnea, whereas in the prone position no change in heart rate could be observed. The present study revealed a position-dependent different impact of apnea on cerebral hemodynamics. With regard to cerebral blood volume and oxygenation in association with apnea no negative effects of prone sleeping position could be observed in preterm infants.

Apnea↗

PubMed2001

A high-resolution phantom for MRI.

Assessment of spatial resolution is an important step to test the performance of new sequence techniques-especially ultrafast techniques with dedicated k-space trajectories or interpolation algorithms. Measurement of the modulation transfer function (MTF) is a rather difficult procedure, but using suitable resolution phantoms allows a simple visual evaluation of spatial resolution. In contrast to commonly used test objects with a very restricted number of resolution patterns we developed a phantom containing resolution patterns from 0.1 to 1.5 mm in steps of 0.1 mm. One resolution pattern consists of five parallel Plexiglas strips with the distance of the strips being equal to their thickness. Together with a Plexiglas cuboid the resolution patterns are mounted on a Plexiglas plate on the bottom of the cylindrical phantom. An aqueous solution of manganese chloride is used to fill the phantom. High resolution cross sections (pixel size: 50 microm) through the resolution patterns were measured to confirm the correct dimensions of the phantom. To verify the appropriateness of the 0.1 and 0.2 mm stacks micro-CT images with a pixel size of 25 microm were acquired additionally for both patterns. Besides visual inspection evaluation of the profile function of signal intensity across the stacks demonstrates that the resolution patterns are sufficiently correct. T(1)-weighted SE sequences with slightly different pixel sizes as well as T(1)- and T(2*)- weighted gradient echo sequences were applied to demonstrate some possible applications of this phantom. In conclusion, the proposed phantom is well suited to assess the spatial resolution qualitatively (i.e., visually) and quantitatively over a wide range in steps of 0.1 mm.

Humans↗

PubMed2001

The reliability of immunohistochemistry as a prescreening method for the diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC)--results of an international collaborative study.

Hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is an autosomal dominant condition accounting for 2-5% of all colorectal carcinomas as well as a small subset of endometrial, upper urinary tract and other gastrointestinal cancers. An assay to detect the underlying defect in HNPCC, inactivation of a DNA mismatch repair enzyme, would be useful in identifying HNPCC probands. Monoclonal antibodies against hMLH1 and hMSH2, two DNA mismatch repair proteins which account for most HNPCC cancers, are commercially available. This study sought to investigate the potential utility of these antibodies in determining the expression status of these proteins in paraffin-embedded formalin-fixed tissue and to identify key technical protocol components associated with successful staining. A set of 20 colorectal carcinoma cases of known hMLH1 and hMSH2 mutation and expression status underwent immunoperoxidase staining at multiple institutions, each of which used their own technical protocol. Staining for hMSH2 was successful in most laboratories while staining for hMLH1 proved problematic in multiple labs. However, a significant minority of laboratories demonstrated excellent results including high discriminatory power with both monoclonal antibodies. These laboratories appropriately identified hMLH1 or hMSH2 inactivation with high sensitivity and specificity. The key protocol point associated with successful staining was an antigen retrieval step involving heat treatment and either EDTA or citrate buffer. This study demonstrates the potential utility of immunohistochemistry in detecting HNPCC probands and identifies key technical components for successful staining.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Prediction of the outcome of genetic testing in HNPCC kindreds using the revised Amsterdam criteria and immunohistochemistry.

BACKGROUND AND AIMS: Hereditary non-polyposis colorectal cancer (HNPCC) may be caused by mutations in the mismatch repair (MMR) genes MLH1, MSH2 or MSH6. Family history (Amsterdam criteria) has traditionally been used to select patients for mutation testing. It has been demonstrated that germline mutations in the MMR genes are associated with lack of the corresponding gene product as assessed with immunohistochemistry (IHC) in tumour specimens. The aim of the study was to assess the value of the Amsterdam criteria II and IHC in predicting germline mutations. METHODS: Fifty-six families that were previously tested for MLH1, MSH2 and MSH6 mutations were selected for this study. All pedigrees were extended and verified and the families were scored according to the original (I) and the revised Amsterdam criteria (II). The probabilities for MLH1 and MSH2 mutations were calculated by logistic regression. In addition, all available tumour material from indexed family members was examined by IHC for the presence of the three gene products. RESULTS: Three out of seven (39%) families where the mutation could be identified complied with the Amsterdam criteria I, while all seven (100%) met the Amsterdam criteria II. All families carrying a MLH1 or MSH2 mutation had > 15% calculated probability of finding a mutation. Tumours from all seven mutation carriers lacked the immunohistochemical expression of the corresponding MMR gene. CONCLUSION: The results indicate that the Amsterdam criteria II in combination with immunohistochemistry of the mismatch repair proteins in tumours may be a cost-effective approach to select families for mutation analysis.

Adaptor Proteins, Signal Transducing↗

PubMed2001

[Intrathoracic goiter--a rare mediastinal tumor].

Intrathoracic, totally ectopic goiters are rare, but have to be considered as a diagnostic possibility in all mediastinal masses. The displacement of the thyroid tissue inferiorly in connection with the embryogenesis of the heart and the large vessels explains the aetiology of the disease. Ectopic goiters are often asymtomatic or oligosymptomatic. They may be classified into two groups according to their location in the anterior or posterior mediastinum. The diagnostic procedures include standard X-ray and CT scan imaging, eventually combined with radionuclide scintigraphy. Once the diagnosis of a intrathoracic goiter is obtained the treatment is surgical (unknown dignity, risk of compression or other symptoms). The approach of choice is through a median sternotomy in case of a anterior location and a posterolateral thoracotomy in case of a posterior location. We discuss the diagnostic and therapeutic approach in 2 patients with mediastinal goiters--one located in the anterior and one in the posterior mediastinum.

Adult↗

PubMed2001

Clostridium perfringens toxin types in hooded seals in the Greenland Sea, determined by PCR and ELISA.

Very little is known about the occurrence of Clostridium perfringens and of diseases caused by this anaerobic bacterium in marine mammals, especially those that are free-living. During a scientific expedition to the Greenland Sea (West Ice) in spring 1999, faeces samples from 70 hooded seals (Cystophora cristata) were taken to isolate C. perfiringens. Subsequently, PCR analysis of the isolates was performed with oligonucleotide primers of the genes encoding the four major lethal toxins (alpha, beta, epsilon and iota) for classification of toxin type and of the genes encoding C. perfringens beta2-toxin and enterotoxin for further subclassification. In addition, a commercial ELISA kit for detection of C. perfringens alpha, beta- and epsilon-toxin was used. C. perfingens was isolated in samples from 38 (54.3%) hooded seals. All isolates were C. perfringens toxin type A (alpha-toxin positive). This is the first report on the occurrence of C. perfringens in this arctic marine mammal species. Myositis and enterotoxemia caused by C. perfrigens were described in other marine mammals and it may be assumed that the pathogenesis of an outbreak of disease is similar to that encountered in terrestrial animals. Although there is some controversy surrounding the enteropathogenicity and virulence of alpha-toxin (concerning enterotoxemia), this study suggests that a possible outbreak of enterotoxemia caused by C. perfringens type A in hooded seals may, however, not be excluded.

Animals↗

PubMed2001

Three cases of C-ANCA-positive vasculitis treated with immunoadsorption: possible benefit in early treatment.

Wegener's granulomatosis is a vasculitic disease predominantly affecting the upper respiratory tract, lungs, and kidneys. Three patients with Wegener's granulomatosis and rapidly progressive glomerulonephritis were treated with an intensified regimen of immunoadsorption (IA) (Excorim or Therasorb) in addition to cyclophosphamide (CYC) and methylprednisolone (PRE). Patient A had been in remission under oral CYC/PRE. The first exacerbation was treated successfully with 4 IA treatments without changing medication. Patient B experienced 3 flares within 1 year, which were treated with 28 IA (3-7 IAs/course), intravenous CYC after each course, and PRE. A fall of creatinine levels from 120 to 190 micromol/L to 100 micromol/L was noted after IA and before administration of CYC. Patient C presented in uremia. Autoantibodies were eliminated by 11 IA treatments parallel to CYC/PRE therapy. They remained within a normal range for >1 year's follow-up; however, kidney function did not return. In conclusion, the observations in Patients A and B suggest a beneficial therapeutic effect of early IA in WG.

Adult↗

PubMed2001

[Technical errors in the application of Graf's hip sonography method].

AIM: The aim of the study is to point out possible examination errors because of a titled transducer, and to analyse their sources. METHODS: The results obtained by experienced examiners using the correct examination technique were compared to results obtained under defined deviations from the standard. With the use of a computer model the course taken by the ultrasound waves in the neonatal hip was simulated and the sonographic image reconstructed. RESULTS: Twisted as well as tilted positions of the transducer lead to significant errors in alpha, the acetabular roof angle. This is in accordance with the computer model predictions. Caudo-cranially tilted probes lead to false-positive, therapeutically relevant incorrect diagnoses. CONCLUSION: The computer simulation predicts a high degree of accuracy of hip sonography in Graf's technique under standard conditions. The effectiveness of sonographic infant hip screening largely depends on the ability to adhere to the standardized approach, minimizing possible errors. A mechanical transducer guide prevents tilting errors by reducing the degrees of variability in positioning the transducer.

Artifacts↗

PubMed2001

[Technique of endoscopic subfascial CO2 insufflation-dissection of perforator veins].

Endoscopic subfascial dissection of perforating veins (ESDP) represents a new additional technique for treatment of greater saphenous system varicosities. We present a modification of ESDP, entitled endoscopic subfascial insufflation-dissection of perforating veins (ESIDP). In ESIDP CO2-insufflation induced enlargement of subfascial space (subfascial pneumocave) facilitates identification and dissection of perforating veins. From 1.1.1998 to 1.7.2000, 150 procedures of ESIDP have been conducted in 127 patients (90 females, 37 males). Identification of incompetent perforating and superficial veins and assessment of deep veins were performed preoperatively using duplex sonography. In addition to a description of the surgical technique, we present an overview about indications for ESIDP and possible ESIDP-related postoperative complications.

Carbon Dioxide↗

PubMed2001

Effect of tilting on cerebral hemodynamics in preterm and term infants.

Tilting is known to cause changes in hemodynamics due to hydrostatic pressure. The present study is an analysis of changes in cerebral hemodynamics measured by near infrared spectroscopy (NIRS) following tilting up and down in preterm and term infants. A significantly different effect of tilting up in comparison to tilting down on total hemoglobin in preterm infants and on the 'hemoglobin oxygenation index' in preterm and term infants was observed. In preterm infants, tilting up and down had a significantly different effect on cerebral blood volume (CBV), with an increase after tilting down and a decrease after tilting up. In term infants, tilting had no significant effect on CBV comparing these two procedures. We think that NIRS provides a good method to measure cerebral hemodynamics following tilting, whereby different reactions in infants of different postconceptional age can be observed.

Blood Volume↗

PubMed2001

Expression of tissue factor in high-grade carotid artery stenosis: association with plaque destabilization.

BACKGROUND AND PURPOSE: The procoagulant protein tissue factor (TF) has been implicated in thromboembolic complications associated with advanced atherosclerosis. In this study, we investigated whether TF expression in high-grade stenoses of the internal carotid artery (ICA) is associated with clinical features of plaque destabilization and addressed the relationship between TF expression and plaque inflammation. METHODS: In 36 consecutive patients undergoing surgery for high-grade ICA stenosis, clinical evidence of plaque instability was provided by the recent occurrence of ischemic symptoms attributable to the stenosis and the detection of cerebral microembolism by means of transcranial Doppler ultrasound monitoring of the ipsilateral middle cerebral artery. Endarterectomy specimens were stained immunocytochemically for TF expression as well as macrophage (CD68) and T cell (CD3) infiltration. RESULTS: Morphologically, TF immunoreactivity was codistributed with plaque inflammation and predominantly localized to CD68+ macrophages. Accordingly, statistical analysis revealed a significant association of TF expression with plaque infiltration by macrophages (P<0.0001) and T cells (P=0.013). Plaques extensively stained for TF (median of TF+ total section area >40% in semiquantitative assessment) were more frequent in symptomatic (12/27) than in asymptomatic patients (1/9). Conversely, plaques exhibiting little TF expression (median of TF+ section area <20%) were more frequent in asymptomatic (3/9) than in symptomatic (1/27) patients (P=0.016). Likewise, we found a highly significant association of TF expression with the occurrence of cerebral microembolism (P=0.008). CONCLUSIONS: Induction of TF at sites of plaque inflammation may play an important role in the destabilization of high-grade ICA stenosis.

Carotid Artery, Internal↗

PubMed2001

Fibromyalgia treatment with intravenous tropisetron administration.

A prospective, randomized, placebo-controlled, multicenter, double-blind trial in fibromyalgia patients demonstrated that peroral daily treatment with 5 mg tropisetron for 10 days produced a significant reduction in pain and other symptoms. The aim of the present study was to determine whether intravenous administration of 2 mg tropisetron daily for a limited period of time would produce quicker and more favorable results. In the first cohort 18 fibromyalgia patients received a single intravenous injection of 2 mg tropisetron. In the second cohort 24 fibromyalgia patients were treated with 2 mg intravenous tropisetron daily for 5 days. Pain intensity was measured with the visual analog scale and the pain score. Pain at tender and control points (dolorimeter) as well as 17 ancillary symptoms before and after treatment were evaluated. Pain intensity was followed-up by means of a patient diary until recurrence. Dolorimetry revealed that a single intravenous injection of 2 mg tropisetron significantly reduced pain and enhanced pain threshold. These effects, however, lasted for only a few days. Of 18 patients in the first cohort, only three showed no response to therapy. Of the 24 patients in the second cohort, 23 showed pain reduction when 2 mg tropisetron was administered daily for 5 days. Pain relief lasted for 2 weeks to 2 months in 20 of these patients. Two patients stopped filling in the pain diary. Twelve ancillary symptoms such as sleep disturbances, fatigue, morning stiffness were also significantly improved by the latter treatment. In the global assessment 16 out of 24 patients showed significant improvement and seven showed slight improvement. Only one patient experienced no improvement. Tolerability was good. In conclusion, intravenous injection of 2 mg of the 5-hydroxytryptamine3 receptor antagonist tropisetron once daily for 5 days produced a longer-lasting therapeutic effect on fibromyalgia symptoms than did peroral daily treatment with 5 mg of this drug. The results achieved are currently being evaluated in a randomized, placebo-controlled, double-blind trial.

Adult↗

PubMed2001

Apolipoprotein E and beta A4-amyloid: signals and effects.

In humans, the apolipoprotein E gene (APOE) is polymorphic with the alleles APOE epsilon 2, 3 and 4 coding for apolipoproteins (Apo) E2, 3 and 4. Apart from age, the APOE epsilon 4 allele represents the most important risk factor in sporadic Alzheimer's disease (AD). Compared to APOE epsilon 3 homozygotes, the histopathological onset of tau pathology is found 1-2 decades earlier but progresses with the same speed. ApoE dose-dependently and specifically increases free intraneuronal calcium levels in the order ApoE4 > ApoE3 > ApoE2. This effect is amplified in the presence of beta A4-peptide. The ApoE effects on calcium are not affected by the blockade of action potentials with tetrodotoxin, or by inhibition of common ApoE binding sites. The calcium channel involved has been identified as a P/Q-type-like channel. Brain tissue ApoE levels differ with respect to APOE alleles and Braak-stage for Alzheimer-histopathology. The production of ApoE in astrocytes is controlled by several receptor/effector systems such as adrenoceptors and cAMP. In the presence of beta A4-peptide fragments, astrocytes stop their synthesis of ApoE resulting in a massive reduction in the bioavailability of ApoE. In the periphery, ApoE directs cholesterol transport and thereby influences its cellular concentrations. In neurons, changes in the concentration of cholesterol influence the phosphorylation status of the microtubule-associated protein tau at sites known to be altered in AD.

Alleles↗

PubMed2001

Short-term treatment of primary fibromyalgia with the 5-HT3-receptor antagonist tropisetron. Results of a randomized, double-blind, placebo-controlled multicenter trial in 418 patients.

We investigated the efficacy and tolerability of short-term treatment with tropisetron, a selective, competitive 5-HT3-receptor antagonist in fibromyalgia. The trial was designed as a prospective, multicenter, double-blind, parallel-group, dose-finding study. We randomly assigned 418 patients suffering from primary fibromyalgia to receive either placebo, 5 mg, 10 mg or 15 mg tropisetron once daily for 10 days. Clinical response was measured by changes in pain score, visual analog scale, tender point count and ancillary symptoms. Responders were prospectively defined as patients showing a 35% or higher reduction in pain score. Treatment with 5 mg tropisetron resulted in a significantly higher response rate (39.2%) than placebo (26.2%) (p < 0.05). In the visual analog scale, the group administered 5 mg tropisetron showed a significant improvement (p < 0.05) and the group administered 10 mg tropisetron showed a nonsignificant clinical benefit. The number of painful tender points was significantly reduced (p = 0.002) in the 5 mg tropisetron group. Regarding ancillary symptoms, the 5 mg tropisetron group showed a significant improvement (p < 0.05) in sleep and dizziness. The patients' overall assessment of efficacy was significantly higher for 5 mg (p = 0.016) and 10 mg (p = 0.002) tropisetron than for placebo. The safety and tolerability of tropisetron was good; gastrointestinal tract symptoms were the most frequently reported adverse events. Short-term treatment of fibromyalgia patients with 5 mg tropisetron for 10 days proved to be efficacious and well tolerated. In this study a bell-shaped dose-response curve was seen.

Adolescent↗

PubMed2000

Size exclusion chromatography does not require pores.

Separation of macromolecules on the basis of their molecular weight by size exclusion chromatography has long been considered to be caused by the geometry-dependent partition of macromolecules between a continuous phase and the porous interior of a gel or cross-linked bead. The volume of a pore accessible to a solute is limited by its relative dimensions, so larger molecules will have access to a smaller volume and will remain in a bead for a shorter time than smaller solutes. Our recent alternate picture proposes that the partition coefficient can be calculated from a thermodynamic model for the free energy of mixing of the solute with the gel phase. Size-dependent exclusion caused by the unfavorable entropy of mixing associated with the partition is predicted; the magnitude of the effect is modified by enthalpic interactions between the solute and the gel phase. This concept is extended here to describe the partition of macromolecules into a layer of terminally attached polymer chains grafted onto a solid bead. Both simple mean field and self-consistent field theory calculations predict size-dependent entropic exclusion. Experimental results obtained with neutral polymer chains grafted onto solid polystyrene latex beads confirm the predictions.

Chromatography↗

PubMed2000

Mice reconstituted with DNA polymerase beta-deficient fetal liver cells are able to mount a T cell-dependent immune response and mutate their Ig genes normally.

The ubiquitously expressed, error-prone DNA polymerase beta (polbeta) plays a role in base excision repair, and the involvement of this molecule in the nonhomologous end joining (NHEJ) process of DNA repair has recently been demonstrated in yeast. Polbeta-deficient mice are not viable, and studies on conditional mutants revealed a competitive disadvantage of polbeta(-/-) vs. wild-type cells. We show here that polbeta-deficient mice survive up to day 18.5 postcoitum, but die perinatally; a circumstance that allowed the investigation of a potential role of polbeta in lymphocyte development by transfer of fetal liver cells (FLC) derived from polbeta(-/-) embryos into lethally irradiated hosts. FLC transfers using mutant cells lead to an almost normal reconstitution of the lymphocyte compartment, indicating that polbeta-deficiency does not prevent V(D)J recombination, which is known to employ factors of the NHEJ pathway. Mice reconstituted with polbeta(-/-) FLC mount a normal T cell-dependent immune response against the hapten (4-hydroxy-3-nitrophenyl) acetyl (NP). Moreover, germinal center B cells from NP-immunized reconstituted mice show normal levels and patterns of somatic point mutations in their rearranged antibody genes, demonstrating that polbeta is not critically involved in somatic hypermutation.

Animals↗

PubMed2000

Rhinosurgical therapy planning via endonasal airflow simulation.

Nowadays, Computational Fluid Dynamics (CFD) methods play an important part in the production process of the automotive industry. Progress in recent years has made possible highly sophisticated airflow-simulation models that are used in engineering for optimization and verification of aerodynamics. The key purpose of the Simulation Tool for Airflow in the human Nose (STAN), developed at the Darmstadt University of Technology in cooperation with the University Hospital in Greifswald, is to use these techniques to support the rhinosurgeon in diagnosis and planning of therapy (Frühauf T, Mlynski G. Simulation and visualization of the air flow in the human nose. Proceedings of the First World Congress on Computational Medicine, Austin, Texas, 1994). A system has been developed that realizes a three-dimensional (3D) reconstruction of the endonasal cavities based on computer tomography (CT) scans. This semiautomatic reconstruction method requires minimal manual intervention. The surface model is used to create an unstructured 3D volume mesh suitable for finite volume simulations. In this way, an individual simulation based on patient-specific data can be realized. At the University Hospital in Greifswald, experimental investigations and measurements are made in nasal models to verify the simulation result. The goal of this project is to investigate individual nasal complaints and to detect respiratory disorders. The surgeon should be able to simulate the disordered respiration before performing a surgical procedure, and thereby increase the effectiveness of surgical planning.

Computer Simulation↗

PubMed2000

Common cytokine receptor gamma chain (gammac)-deficient B cells persist in T cell-deficient gammac-mice and respond to a T-independent antigen.

Defects in the common cytokine receptor gamma chain (gammac) in man result in X-linked severe combined immunodeficiency disease (SCIDX1) characterized by an absence of alphabeta T cells, gammadelta T cells and NK cells, with the presence of circulating B cells. Mice made deficient for gammac lack gammadelta T cells and NK cells, but in contrast to SCIDX1 patients have appreciable numbers of alphabeta T cells, while B cells are reduced about tenfold in numbers and disappear with age. Here we show that when gammac- mice are rendered T cell deficient, B cell numbers are still reduced but the age-dependent loss of B cells does not occur. The peripheral B cells which persisted in gammac-/ nude and gammac-/TCRbeta-/- mice were able to respond to mitogen stimulation in vitro and to mount antigen-specific T-independent Ig responses in vivo. These results demonstrate that gammac- B cells are functionally competent and suggest that residual alphabeta T cells are implicated in the B cell loss in gammac mice. The gammac-/nude and gammac-/TCRbeta-/- mice provide new models to dissect the role of gammac-dependent receptors during murine B cell differentiation.

Animals↗