Biomedical subjects

M Müller

Publications and source records attributed to M Müller.

At least 37 records · Page 2Linked to original sources

PubMed2006

5-aminosalicylic acid release from a new controlled-release mesalazine formulation during gastrointestinal transit in healthy volunteers.

BACKGROUND: Mesalazine (5-aminosalicylic acid, 5-ASA) containing formulations represent a cornerstone in the treatment of inflammatory bowel diseases. A novel formulation with an Eudragit L/S mixture coating has been developed to provide selective release of 5-ASA to the ileo-caecal region and the colon. AIM: To determine the release of 5-ASA during the gastrointestinal transit. METHODS: A single oral dose of mesalazine EC 500 mg gastroresistant tablets (Asamax) was administered to eight healthy male volunteers. Gastrointestinal transit and tablet disintegration were monitored by scintigraphy. 5-ASA release was verified by assessing plasma pharmacokinetics. RESULTS: Initial tablet disintegration was observed 5.65 +/- 0.86 h after dosing, corresponding to the detection of 5-ASA in plasma. This occurred in the ileo-caecal region in three subjects and the ascending colon in the remaining five. The relative percentage of 5-ASA absorption was more pronounced in the ascending colon (41 +/- 27.4%) than the ileo-caecal region (6.6 +/- 9.2%). CONCLUSION: This mesalazine EC gastroresistant tablets release locally active 5-ASA specifically in the ileo-caecal region and the ascending colon.

Administration, Oral↗

PubMed2006

Nanostructured niobium oxide coatings influence osteoblast adhesion.

The interaction of osteoblasts was correlated to the roughness of nanosized surface structures of Nb(2)O(5) coatings on polished CP titanium grade 2. Nb(2)O(5) sol-gel coatings were selected as a model surface to study the interaction of osteoblasts with nanosized surface structures. The surface roughness was quantified by determination of the average surface finish (Ra number) by means of atomic force microscopy. Surface topographies with Ra = 7, 15, and 40 nm were adjusted by means of the annealing process parameters (time and temperature) within a sol-gel coating procedure. The observed osteoblast migration was fastest on smooth surfaces with Ra = 7 nm. The adhesion strength, spreading area, and collagen-I synthesis showed the best results on an intermediate roughness of Ra = 15 nm. The surface roughness of Ra = 40 nm was rather peaked and reduced the speed of cell reactions belonging to the adhesion process.

3T3 Cells↗

PubMed2006

[Helical computed tomography in penetrating injury to the torso. Diagnostic value in emergent use].

BACKGROUND: Nontherapeutic laparotomy and thoracotomy rates in penetrating torso trauma remain high. The aim of this study was to define the value of helical computed tomography (CT) in this emergency situation. MATERIAL AND METHODS: Retrospectively, we studied 11 hemodynamically stable patients with penetrating injury to the torso admitted to our trauma center over a 3-year period who underwent intravenous contrasted helical CT immediately after admission. A positive CT scan was defined as showing any evidence of intrathoracal or intra-abdominal injury necessitating immediate operation. Patients with positive CT underwent laparotomy and/or thoracotomy. Patients with negative CT were observed. RESULTS: Eleven consecutive patients were studied: nine male, two female; mean age 39 years (range 19-62). Nine stab wounds and two shotgun wounds were seen. Seven patients had positive helical CT findings, and four patients were negative. All patients with positive CT findings were operated on; those with negative scans recovered uneventfully. This imaging method accurately predicted whether thoracotomy or laparotomy was needed in 10/11 cases. CONCLUSION: In penetrating torso trauma, helical CT can clarify the need for thoracotomy or laparotomy vs nonoperative treatment.

Abdominal Injuries↗

PubMed2006

[Postoperative CT-controlled results of renewed osteosynthesis using screw fixation for acute scaphoid fractures].

BACKGROUND: Currently screw fixation of the scaphoid is a well-established method to treat unstable scaphoid fractures. PATIENTS AND METHODS: Between June 1995 and December 2000, 68 patients with an unstable acute scaphoid fracture were treated with screw fixation; 46 patients were reexamined on an average 35 months postoperatively. Range of motion and grip strength (Jamar dynamometer) were measured. The total data rating resulted from the Krimmer wrist score. RESULTS: The subjective results were evaluated with the DASH questionnaire. The average postoperative pain score was documented with a visual analogous pain scale from zero to 100 (VAS 0-100). X-rays as well as computed tomography were performed postoperatively. The average range of motion was 124 degrees for extension/flexion (92% of the opposite site), 57 degrees for radial/ulnarduction (=90%), and 177 degrees for pronation/supination (=98%). Postoperative strength was 47 kg (=90% of the opposite site). The postoperative pain score was 13 (0-100) after stress and 2 during resting conditions. Bony consolidation was reached in 44 cases. The Krimmer wrist score demonstrated a very good result in 39 cases, a good result in 5 cases, and a satisfactory result in 3 cases. The average DASH score was 8.3 points. CONCLUSIONS: The results demonstrate the reliability of internal screw fixation as treatment for acute scaphoid fractures. Functional results as well as subjective satisfaction of the patients are very good. Postoperative CT scans help to evaluate exact bony consolidation, position of the screw, and postoperative morphology of the scaphoid.

Adolescent↗

PubMed2006

[Norian SRS augmentation in revision of acetabular cup of total hip arthroplasty. A follow up of six patients].

This article reports on bony acetabular reconstruction combined with load-bearing cementation of the acetabular components in revision hip arthroplasty. In six cases bone defects were filled with osteoconductive cement Norian SRS--if needed after cancellous bone grafting. Thereupon the primary load stable cementation of an acetabular reconstruction ring or an acetabular basket was done in combination with cementation of an inlay. Patients were examined according to the scores of Harris and Merle d'Aubigné. The patient's satisfaction was used as another criterion and X-rays were taken upon consent. Four of five patients included in the evaluation achieved good or excellent results.

Acetabulum↗

PubMed2006

[Preventing malrotation during intramedullary nailing of femoral fractures].

BACKGROUND: The problem of preventing malrotation after closed intramedullary nailing of femoral shaft fractures has not been solved yet. As clinical tests and radiologic criteria for intraoperative use provide little accuracy, the theoretical basis for a C-arm-based measurement of the femoral antetorsion was analysed. METHODS: The directions of femoral neck axis and condylar axis can be identified by the radiologic views "knee joint, lateral view" and "hip joint, axial view". The rotation of the C-arm in relation to a horizontal axis to achieve these views can be measured in degrees. Theoretically, the difference between these rotation angles could be used to calculate the antetorsion. Intact plastic femora (Sawbone) and a femoral shaft fracture model were used to research optical and geometrical phenomena that influence a direct measuring technique. RESULTS: Several geometrical phenomena were observed, making direct measurement with arithmetic corrective factors not recommendable. For practical reasons, a data table was created, correlating the difference between the two C-arm angles with true antetorsion. In an interobserver trial with 18 trauma surgeons, the method proved to achieve high accuracy with a maximum interobserver variation of 5 degrees. CONCLUSIONS: The method is easily reproducible, reliable and can be recommended to every surgeon. Due to the wide range of physiological antetorsion angles in different individuals, fair results can be expected controlling the rotation with standard value tables, and excellent results can be expected using bilateral measurement.

Femoral Fractures↗

PubMed2006

[A complication during kyphoplasty. Cement penetration through the azygos vein into the superior vena cava].

A 59-year-old woman had a nontraumatic osteoporotic fracture of the seventh thoracic vertebral body. Despite correct operative technique, in the course of kyphoplasty cement was dislocated through the segment vein into the azygos vein and from there into the superior vena cava. The patient was free of cardiopulmonary symptoms throughout. Oral anticoagulation was administered for 3 months to prevent thromboembolism, and regular clinical and echocardiographic follow-up examinations were also performed during this period.

Bone Cements↗

PubMed2006

pH dependence and protein selectivity of poly(ethyleneimine)/poly(acrylic acid) multilayers studied by in situ ATR-FTIR spectroscopy.

The selective interaction between polyelectrolyte multilayers (PEM) consecutively adsorbed from poly(ethyleneimine) (PEI) and poly(acrylic acid) (PAC) and a binary mixture containing concanavalin A (COA) and lysozyme (LYZ) based on electrostatic interaction is reported. The composition and structure of the PEM and the uptake of proteins were analyzed by in situ attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy, and the morphology and thickness were characterized by atomic force microscopy (AFM) and ellipsometry. The PEM dissociation degree and charge state and the protein adsorption were shown to be highly dependent on the outermost layer type and the pH in solution. High protein uptake was obtained under electrostatically attractive conditions. This was used to bind selectively one protein from a binary mixture of LYZ/COA. In detail it could be demonstrated that six-layered PEM-6 at pH = 7.3 showed a preferential sorption of positively charged LYZ, while at PEM-5 and pH = 7.3 negatively charged COA could be selectively bound. No protein sorption from the binary mixture was observed at pH = 4.0 for both PEM, when COA, LYZ, and the outermost PEI layer of PEM-5 were positively charged or the outermost PAC layer of PEM-6 was neutral. Furthermore, from factor analysis of the spectral data the higher selectivity was found for PEM-5 compared to PEM-6. Increasing the ionic strength revealed a drastic decrease in the selectivity of both PEM. Evidence was found that the proteins were predominantly bound at the surface and to a minor extent in the bulk phase of PEM. These results suggest possible working regimes and application fields of PEI/PAC multilayer assemblies related to the preparative separation of binary and multicomponent protein mixtures (biofluids, food) as well as to the design of selective protein-resistant surfaces.

Acrylic Resins↗

PubMed2006

[Laparoscopic pancreatic resection].

UNLABELLED: Over a long time laparascopy for pancreatic diseases was performed only as staging laparoscopy in order to find hidden metastasis. The laparoscopic pyloric preserving duodeno-pancreatectomy showed many problems and could not establish. Laparoscopic distal resection of pancreas is much more feasible due to lack of intestinal anastomoses. Anyway there is only few literature about laparoscopic left pancreatic resection found. We demonstrate our experiences in four cases of the last months. RESULTS: In all four cases laparoscopic distal pancreatic resection was performed for tumor. In three cases the resection of the spleen was necessary. In another case we performed a laparoscopic hemifundoplicaton (DOR) for GERD in the same session. Histologic examination showed a neuroendocrine carcinoma, a serous-microcystic adenoma, a low differentiated ductal adenocarcinoma and an intraductal papillary-mucinous tumor of borderline type. Postoperative stay was between eight and ten days. There was no patient suffering from intra- or postoperative complications. CONCLUSION: Laparoscopic resection of distal pancreas shows the common benefit of minimal invasive surgery for the early postoperative period and is an attractive alternative for treatment of benign and semimalign pancreatic tumors.

Adenoma↗

PubMed2006

[Laparoscopic Dor-hemifundoplication for therapy of gastroesophageal reflux disease].

INTRODUCTION: Gastroesophageal reflux disease is a major health problem in western industrial nations. Several prospective randomized studies showed the operative therapy of GERD superior to a steady medication with omeprazole regarding recurrence rate as well as rate of side effects. The today most performed 360 degrees fundoplication (Nissen-Rossetti) leads in 10-30% to a persisting postoperative dysphagia. We prefer the anterior semifundoplication by Dor. Aim of our study is to find out if our results are comparable to current literature and to open procedure. PATIENTS: Between 1.1.03 and 30.6.05 one operator performed on 100 consecutive patients (57 female, 43 male) between 29 and 86 years of age an anterior Dor-semifundoplication with posterior hiatal repair. In 37 cases we performed a cholecystectomy simultaneously, on two patients a sigmoid resection and in one case a left pancreatic resection. 52 Patients were re-evaluated after six months (median follow up nine months). RESULTS: Median operation time was 71 min (30-250 min). The learning curve showed a time reduction of initially 102 to 40 min in the last 10 cases. Blood loss was between 10 and 300 ml (median 40 ml). No conversion was necessary). As intraoperative complication in one case the right pleural cavity was opened. Postoperative complications were found to be wound infection in one case and urinary tract infection in another. Postoperative stay was four days (2-19 d) and eight days respectively for patients after sigmoid resection or left pancreatic resection. After median follow up of nine months 45 of 52 re-evaluated patients (86%) were free of reflux symptoms, 47 (90%) were pleased or very pleased with the result of the operation. Four patients felt at least a reduction of preoperative symptoms. CONCLUSION: The anterior Dor semifundoplication is a technically easy and low risk procedure, which has a lower side effect rate than the 360 degrees operation and will heal 90% of the patients from their reflux disease.

Adult↗

PubMed2006

[Extent of lymphnode dissection with minimally invasive esophageal resection].

UNLABELLED: Esophageal resection is still today associated with a high morbidity and mortality. Minimally invasive procedures show a significantly lower rate of such complications and therefore might also be associated with a lower surgical risk. However, publications till date contain little or no data on the extent of lymph node dissection. The aim of our study was to evaluate the morbidity and mortality rate of minimally invasive esophageal resection. MATERIAL AND METHODS: In the last two years, we carried out 25 minimally invasive esophageal resections on five women and 20 men with a median age of 63 years (range 41-74 years). All data were accrued prospectively. RESULTS: Nine patients were operated upon transhiatally and 12 combined laparocopic-thoracoscopic. On four patients, a thoracotomy was necessary. The average surgical time for the transhiatal approach was calculated at 164 minutes (range 150-180 min) and for the combined laparoscopic-thoracoscopic procedure 285 minutes (240-360 min). The thoracoscopic esophageal resection itself lasted 105 minutes on average; the last five resections each lasting 70 minutes. A median of 24,5 lymph nodes (19-26) was calculated in the laparoscopic-thoracoscopic technique. The transhiatal procedure revealed a median of 14 lymph nodes (12-17). Postoperatively, we had three cases of anastomotic and two cases of bronchial leakages, most probably associated with the use of monopolar current; complications no longer seen since usage of the HARMONIC ACE for surgical preparation. There was no 30 day letality. CONCLUSION: Our experience with 25 successful minimally invasive esophageal resections shows that with increasing experience and better surgical equipment, the extent of lymph node dissection does not differ from open procedure.

Adenocarcinoma↗

PubMed2006

Gastrointestinal transit, release and plasma pharmacokinetics of a new oral budesonide formulation.

AIMS: The aims of the study were to: (1) evaluate the gastrointestinal transit, release and absorption of budesonide from tablets with a new multimatrix formulation (MMX) designed to release the drug throughout the whole colon, and (2) assess the influence of food on budesonide bioavailability. METHODS: Two phase I studies, each comprising 12 healthy males, were performed. Gastrointestinal transit of (153)Sm-labelled tablets containing 9 mg budesonide was evaluated by means of pharmaco-scintigraphy. The effect of food was tested by comparing plasma pharmacokinetics after intake of a high fat and high calorie breakfast with fasting controls. RESULTS: (153)Sm-labelled tablets reached the ascending colon after a mean +/- SD 9.8 +/- 6.9 h. Initial tablet disintegration was observed in the ileum in 42% and the ascending and transverse colon in 33% of subjects. Ninety-six per cent of the dose was absorbed into the systemic circulation during passage through the whole colon including the sigmoid. Food significantly decreased C(max) values from 1429 +/- 1014 to 1040 +/- 601 pg mL(-1) (P = 0.028) and AUC values from 14 814 +/- 11 254 to 13 486 +/- 9369 pg h(-1) mL(-1) (P = 0.008). Mean residence time and t(max) increased by 12-29%. There was no drug accumulation after 1 week of once daily oral administration of budesomide. CONCLUSIONS: MMX-budesonide tablets appear suitable for targeted colonic drug delivery. Transit parameters and low systemic bioavailability warrant further studies with the new formulation.

Absorption↗

PubMed2006

Induction of early murine cytomegalovirus infection by different reporter gene-associated recombinant viruses.

Murine cytomegalovirus (MCMV) has provided useful models for acute, chronic and latent CMV infection because of its similarities in structure and biology with human CMV. We report the induction of acute MCMV hepatitis with different bacterial artificial chromosome (BAC)-cloned virus constructs [MCMV-SEAP which includes the gene for secreted alkaline phosphatase (SEAP) under Rous sarcoma virus (RSV)-promoter control, MCMV-GFP which includes the gene for enhanced green fluorescent protein (eGFP) under HCMV-ie promoter control, MCMV-HBs includes the gene for hepatitis B surface antigen (HBsAg) under simian virus (SV)40-promoter control and the DeltaMC95.21 virus in which the m152 gene was deleted and substituted by the reporter gene lacZ] in order to elucidate the histopathological changes together with different reporter-gene products in the liver tissue and the effect of the deletion of a certain gene. All the virus constructs induced a similar mild acute hepatitis which had its climax from days 3 to 5 post-infection in immunocompetent mice. In situ, the reporter-gene products beta-galactosidase and secreted alkaline phosphatase could be visualized in relation to the inflammatory changes. The composition of the invading cell populations did not change even in the absence of the m152 gene. Additionally discrete inflammatory changes were seen in kidney and serosa while the other organs were not involved. This model helps us understand the immunological and histopathological mechanisms of the CMV-induced hepatitis, which plays an important role especially in the immunocompromised patient. The morphological changes can be analysed while the respective reporter gene product is expressed by the virus construct.

Acute Disease↗

PubMed2006

Biosynthetic gene cluster for the polyenoyltetramic acid alpha-lipomycin.

The gram-positive bacterium Streptomyces aureofaciens Tü117 produces the acyclic polyene antibiotic alpha-lipomycin. The entire biosynthetic gene cluster (lip gene cluster) was cloned and characterized. DNA sequence analysis of a 74-kb region revealed the presence of 28 complete open reading frames (ORFs), 22 of them belonging to the biosynthetic gene cluster. Central to the cluster is a polyketide synthase locus that encodes an eight-module system comprised of four multifunctional proteins. In addition, one ORF shows homology to those for nonribosomal peptide synthetases, indicating that alpha-lipomycin belongs to the classification of hybrid peptide-polyketide natural products. Furthermore, the lip cluster includes genes responsible for the formation and attachment of d-digitoxose as well as ORFs that resemble those for putative regulatory and export functions. We generated biosynthetic mutants by insertional gene inactivation. By analysis of culture extracts of these mutants, we could prove that, indeed, the genes involved in the biosynthesis of lipomycin had been cloned, and additionally we gained insight into an unusual biosynthesis pathway.

Anti-Bacterial Agents↗

PubMed2006

Concomitant down-regulation of SPRY1 and SPRY2 in prostate carcinoma.

Sprouty proteins encoded by the SPRY genes act as modulators and feedback inhibitors of signalling by epidermal growth factor (EGF) and fibroblast growth factor (FGF). Overactivity of EGF and FGF signalling common in prostate cancer might therefore be exacerbated by Sprouty down-regulation. Indeed, down-regulation of SPRY1 and SPRY2 expression has been independently reported. We found both genes modestly down-regulated by microarray expression analysis of microdissected prostate cancers and by quantitative RT-PCR in macrodissected specimens compared with benign tissues. Importantly, the decreases paralleled each other and expression levels of both genes were significantly lower in cancers that recurred within the average follow-up period of 32 months. In contrast to a previous report, no hypermethylation was found to accompany down-regulation of SPRY2 in cancer tissues and cell lines. We additionally investigated the expression of an SPRY1 alternative transcript presumed to be specific for fetal tissues and found its expression moderately well correlated with expression of the standard transcript through diverse tissues and cell lines. The present study confirms and extends previous reports by demonstrating concomitant down-regulation and a significant association with recurrence of SPRY genes.

Cell Line, Tumor↗

PubMed2006

Plasma pharmacokinetics of desmopressin following sublingual administration: an exploratory dose-escalation study in healthy male volunteers.

OBJECTIVE: Desmopressin is usually administered intranasally in the treatment of central diabetes insipidus or nocturnal enuresis. The sublingual administration of desmopressin is expected to be an alternative to the intranasal route with advantages to children and to patients with allergic rhinitis or chronic rhinosinusitis. Therefore, the present study was carried out to explore the time-versus-concentration profile of desmopressin in plasma after sublingual administration to healthy volunteers. SUBJECTS AND METHODS: A total of 16 healthy male volunteers were enrolled in this open, exploratory, 1-period, randomized, dose-escalation study. Volunteers received a single sublingual dose of either 20, 40, 80, 160, 240 or 320 microg of desmopressin acetate. Desmopressin plasma concentrations were measured over a 12-hour period using a validated radioimmunoassay method. Safety and tolerability were assessed simultaneously. RESULTS: Plasma concentrations of desmopressin were below the lower limit of quantification (LLOQ) of 5 pg/ml for doses lower than 80 microg. For the doses of 160 - 320 microg the time-versus-concentration profiles were higher than the LLOQ. The area under the curve from 0 - 12 h (AUC0-12h) was 54.66 +/- 25.92 pg x h/ml after the 160 microg dose, 104.38 +/- 79.10 pg x h/ml following the 240 microg dose and 133.18 +/- 181.84 pg x h/ml following the 320 microg dose. Given the data from previous experiments, the time-versus-concentration profile of desmopressin in plasma after a sublingual dose of 240 microg appeared to be in the range of previously published data on an intranasal dose of 20 microg. Sublingual administration of desmopressin proved to be safe and was well tolerated by all volunteers. CONCLUSION: A very high inter-individual variability in desmopressin plasma concentrations was detected after sublingual administration. A sublingual dose of 240 microg of desmopressin appeared to result in a pharmacokinetic profile comparable to 20 microg administered intranasally. These data, however, need to be verified in a separate well-designed prospective clinical study.

Administration, Oral↗

PubMed2006

[Case report: mast cell leukosis in a neonatal calf].

Multicentric mast cell tumours in a newborn Fleckvieh-calf are described. The calf showed clearly pronounced lesions over the whole body. The lesions were multiple raised, cutaneous, greyisch-red and partially ulcerated. It died three hours after birth. Pathohistological examinations resulted in multiple mast cell tumours within the dermis. In addition multifocal to diffuse mast cell aggregations were observed in several internal organs including the lymph nodes and the bone marrow. No evidence for the presence of bovine leukemia virus was found by both investigating a lymph node homogenate of the calf and a blood sample of the mother cow. In this paper the pathomorphology of this rare disease is described, a possible cause is discussed and a short review of the available literature is presented.

Animals↗

PubMed2005

Phonon modes at the 2H-NbSe2 surface observed by grazing incidence inelastic x-ray scattering.

We have determined the dispersion of acoustic and optical surface phonon modes 2H-NbSe2 at the by inelastic x-ray scattering under grazing incidence conditions. Already, at room temperature, an anomaly is observed close to the charge density wave -vector position located at about one-third along the Gamma-M direction of the Brillouin zone. Our results indicate that the anomaly for the surface mode occurs at a lower energy than that measured in bulk sensitive geometry in the same experiment, showing evidence of a modified behavior in the uppermost layers. We demonstrate that inelastic x-ray scattering in grazing incidence conditions provides a unique tool to selectively study either surface or bulk lattice dynamics in a single experiment.

Journal Article↗