Biomedical subjects
Publications and source records attributed to M Walter.
Esophageal perforations are rare but most often caused by instrumental lesions during endoscopy. We describe a cases of the iatrogen esophageal perforation accompanied with perforation of the pericardium. Chest radiograph with Gastrografin swallow revealed the perforation. The principles of operative treatment and the postoperative course are demonstrated.
A novel prokaryotic expression vector pGEX-6T was designed for high-level expression of recombinant fusion protein with a histidine-hexapeptide and glutathione-S-transferase at its N-terminus and the recombinant human preproinsulin at its C-terminus. Efficiency of expression was investigated in the Escherichia coli strain CAG456. The synthesized protein was sequestered in an insoluble form in inclusion bodies and was purified to homogeneity by one-step affinity chromatography based on the specific complex formation of the histidine-hexapeptide and a chelating matrix which was charged with Ni2+ ions. The antigenic nature of the purified recombinant preproinsulin fusion protein was evaluated by ELISA screening for insulin autoantibodies in selected sera from patients with recent-onset type 1 (insulin-dependent) diabetes mellitus classified by the existence of additional autoantibodies reactive against glutamic acid decarboxylase. 14% of the tested sera (n = 43) contained insulin autoantibodies which strongly recognized the recombinant human preproinsulin. Comparable measurements with both recombinant human preproinsulin and mature insulin suggested that the observed autoantigenicity of preproinsulin was mediated by the C-peptide or/and signal peptide.
Sry is expressed at higher levels in the adult testis, where no function has been determined, than in the genital ridge, its critical site of action. cDNA and 5' RACE clones isolated from testis or from Sry-transfected cell lines have an unusual structure, with 3' sequences located in a 5' position. RNAase protection assays and reverse transcription polymerase chain reactions confirmed that these unusual RNA molecules represent the most abundant transcript in testis. Furthermore, oligonucleotide hybridization and RNAase H digestion proved that these Sry RNA molecules are circular. Similar transcripts were detected in the testes of mice with Mus musculus musculus, Mus musculus domesticus, and Mus spretus Sry genes. The circular RNA is found in the cytoplasm but is not substantially bound to polysomes. We suggest that the circles arise from normal splicing processes as a consequence of the unusual genomic structure surrounding the Sry locus in the mouse.
We have studied a controlled-release formulation containing metoprolol 100 mg and hydrochlorothiazide 12.5 mg. We compared the pharmacokinetics of both substances and the pharmacodynamics of metoprolol with those of a conventional combination tablet. The controlled-release formulation gave less variable plasma metoprolol concentrations, Cmax 138 nmol.l-1 and Cmin 74 nmol.l-1, whereas for the conventional formulation the mean Cmax of metoprolol was 629 nmol.l-1 and the Cmin 20 nmol.l-1. Despite lower relative systemic availability (68%) for metoprolol from the controlled-release formulation and a smaller AUC, metoprolol from the controlled-release formulation produced a greater total effect, calculated as the area under the curve of the effect on exercise heart rate vs. time (303 vs. 259%.h; P < 0.05). Hydrochlorothiazide was rapidly absorbed from both formulations and the plasma concentration profiles were almost superimposable. Controlled-release metoprolol with hydrochlorothiazide combines effective beta 1-adrenoceptor blockade for 24 h without affecting the pharmacokinetics of hydrochlorothiazide.
Sagittal condylar path angles and the position of the lower dental arch in relation to the hinge axis were recorded in 101 edentulous patients wearing new complete dentures. The procedure was based on the method described by Gerber. From the results radii of fictitious compensating curves adjusted for non-anatomical teeth were derived. These compensating curves can be put into the practice of denture construction by using spherical templates in tooth arrangement. Required template radii were found to range from 70mm to 550mm (median 110mm).
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Centrosomes are undetectable in unfertilized sea urchin eggs, and normally the sperm introduces the cell's microtubule-organizing center (MTOC) at fertilization. However, artificial activation or parthenogenesis triggers microtubule assembly in the unfertilized egg, and this study explores the reappearance and behavior of the maternal centrosome. During activation with A23187 or ammonia, microtubules appear first at the cortex; centrosomal antigen is detected diffusely throughout the entire cytoplasm. Later, the centrosome becomes more distinct and organizes a radial microtubule shell, and eventually a compact centrosome at the egg center organizes a monaster. In these activated eggs, centrosomes undergo cycles of compaction and decompaction in synchrony with the chromatin, which also undergoes cycles of condensation and decondensation. Parthenogenetic activation with heavy water (50% D2O) or the microtubule-stabilizing drug taxol (10 microM) induces numerous centrosomal foci in the unfertilized sea urchin egg. Within 15 min after incubation in D2O, numerous fine centrosomal foci are detected, and they organize a connected network of numerous asters which fill the entire egg. Taxol induces over 100 centrosomal foci by 15 min after treatment, which organize a corresponding number of asters. The centrosomal material in either D2O- or taxol-treated eggs aggregates with time to form fewer but denser foci, resulting in fewer and larger asters. Fertilization of eggs pretreated with either D2O or taxol shows that the paternal centrosome is dominant over the maternal centrosome. The centrosomal material gradually becomes associated with the enlarged sperm aster. These experiments demonstrate that maternal centrosomal material is present in the unfertilized egg, likely as dispersed undetectable material, which can be activated without paternal contributions. At fertilization, paternal centrosomes become dominant over the maternal centrosomal material.
Spieghelian hernia is a rare rupture of the abdominal wall along the linea semilunaris. Due to the fact that the rupture is overlain by the aponeurosis of M. externus abdominis, it is often not recognized in its early stage. In most cases the rupture neck is mostly very narrow and in 24.1% of all cases an incarceration of intestinal parts has ensued which may even lead to the development of an acute abdomen. The first choice therapy will consist in an operative support including the reposition of the hernial content and a possible resection of ischaemic organs as well as removal and sealing of the hernia. Because of the rarity of this sickness we report on a patient in our clinic who was operated as an emergency.
An experimental study on a new biologic vascular graft for reconstruction of small diameter arteries was carried out in 50 sheep. A follow-up period of two years let us conclude that the new vascular prosthesis may be "re-utilized" by the host. Infection and aneurysmatic degeneration could not be observed. An early occlusion of the graft occurred in only one case, due to technical reasons.
We have analyzed the translocation of hepatitis B virus (HBV) precore (PC) proteins by using Xenopus oocytes injected with a synthetic PC mRNA. The PC region is a 29-amino-acid sequence that precedes the 21.5-kDa HBV capsid or core (C) protein (p21.5) and directs the secretion of core-related proteins. The first 19 PC amino acids provide a signal peptide that is cleaved with the resultant translocation of a 22.5-kDa species (p22.5), in which the last 10 PC residues precede the complete p21.5 C polypeptide. Most p22.5 is matured to 16-20 kDa species by carboxyl-terminal proteolytic cleavage prior to secretion. Here we show that some four unexpected PC proteins of 24 to 25 kDa are produced in addition to the secretion products described above. Protease protection and membrane cosedimentation experiments reveal that all PC proteins behave as expected for proteins that are translocated into the lumen of the endoplasmic reticulum except for the single largest PC protein (p25), which is not translocated. Like p21.5, p25 is a phosphoprotein that localizes to the oocyte cytosol and nucleus, and protease digestion studies suggest that the two molecules have similar two-domain structures. Radiosequencing of immobilized p25 demonstrates that it contains the intact PC signal peptide and represents the unprocessed translation product of the entire PC/C locus. Thus, while many HBV PC protein molecules are correctly targeted to intracellular membranes and translocated, a significant fraction of these molecules can evade translocation and processing.
Clinical ergotism as seen today results almost exclusively from the intake of ergotamine tartrate in the treatment of migraine headache. Vasospasm of peripheral arteries is the leading clinical picture. Besides the formation of collaterals and a secondary thrombosis, the vasospasm is one of the specific findings in arteriography. Early diagnosis and withdrawal of the medication makes complete restitution possible. In all other cases intraarterial or intravenous infusion of sodium nitroprusside has turned out to be the most effective therapy. Balloon dilatation or operative intervention are an alternative therapy in those cases, where amputation of the limbs seems to be necessary.
The compartment syndrome, a well known complication in traumatized patients, is not taken enough notice of in the literature of vascular surgery despite it's obviously important pathophysiological context. Considering arterial occlusive disease the ischemia as well as the reperfusion can increase the compartmental volume respectively the tissue pressure. The subfascial pressure measurement should not lead to a false certainty, since no critical pressure values exist that can serve as a general criterion for diagnosis and treatment. The "thought about it" may be the first step to a clinical diagnosis and subsequent therapy. Decompression of all four compartments at the lower leg by the technique of Matsen represents the therapy of choice for the compartment syndrome of the lower leg.
A total of 37 patients was provided with complete dentures according to the calotte system. Two groups were formed with regard to the arrangement of the anterior teeth. After a mean period of wear amounting to 13 months different positions of the mandible were recorded in 21 patients under the guidance of a central bearing point and in occlusion. Patients with an arrangement of the anterior teeth free of interferences in excursive movements exhibited a significantly lower distance habitual occlusion/retruded position than subjects with an overlap limiting sagittal freedom. Therefore, an arrangement of the anterior teeth integrated into the calotte complex respectively free of interferences in eccentric positions is to be preferred.
Studies in severe chronic stable heart failure (HF) indicate that pulmonary resistance might remain unchanged during exercise and could subsequently contribute to limitation in exercise capacity of these patients. We assessed the possible role of the exercise decreases in mixed venous oxygen tension on this phenomenon in fifteen patients with chronic congestive heart failure (N.Y.H.A. functional classes II to IV) who underwent a symptom-limited treadmill exercise test with hemodynamic monitoring as well as repeated arterial and mixed venous blood gas analysis. For all patients there was an increase in cardiac output (from 3.7 +/- 0.2 to 6.7 +/- 0.5 l/min, p less than 0.001) and pulmonary wedge pressure (from 16 +/- 2 to 31 +/- 3 mm Hg, p less than 0.001) along with exercise with highly significant decrease in total systemic resistance and no significant (from 25.6 +/- 1.5 to 15.8 +/- 1.0 U, p less than 0.001) changes in pulmonary vascular resistances. Arterial blood oxygen tension increased from 86 +/- 3 to 99 +/- 3 mm Hg (p less than 0.001) and mixed venous oxygen tension (PvO2) decreased from 33 +/- 1 to 22 +/- 1 mm Hg (p less than 0.001). Changes in pulmonary vascular resistance during exercise were inversely related to changes in PvO2 (r = -0.61; p less than 0.05). We conclude that the observed decrease in PvO2 might be a determinant of unchanged pulmonary vascular resistance during treadmill-exercise test in severe heart failure patients.
In spite of the revolutionary innovations concerning diagnostic and intensive care techniques as well as better understanding of tumour biology during the last decade, rates of resection and long-term survival in bronchogenic carcinoma could not be improved. Nevertheless there is no reason for therapeutic nihilism. On the contrary all efforts are to be done in investigation on practicable, suitable, and supportable screening programmes to improve the patients outcome.
ApoA-I and apoC-II are eluted in two isoforms and apoC-III2 is eluted in three isoforms by reversed phase high performance liquid chromatography (HPLC). The structural basis of these nongenetic heterogeneities was unravelled using HPLC of proteolytic peptides and time-of-flight secondary ion mass spectrometry (TOF-SIMS). In apoA-I, the chromatographic microheterogeneity was caused by the formation of methionine sulfoxides (MetSO). However, only residues Met112 and Met148 were found oxidized, whereas Met86 was unaffected and also resistant towards artificial oxidation. To assess whether and to what extent amino acid substitutions in apoA-I might affect methionine sulfoxidation, the tryptic peptides of 13 different mutant apoA-I proteins from 24 heterozygous apoA-I variant carriers were analyzed by HPLC. In normal apoA-I, the ratios MetSO112/Met112 and MetSO148/Met148 were highly variable. By contrast, the relative ratio of oxidation of methionine residues 112 and 148 was constant. The amino acid changes Lys107----Met, Lys107----O, Glu139----Gly, Glu147----Val, and Pro165----Arg resulted in the preferential oxidation of Met112, and Asp103----Asn resulted in a preferential oxidation of Met148; whereas Pro3----Arg, Pro3----His, Pro4----Arg, Asp89----Glu, Ala158----Asp, Glu198----Lys, and Asp213----Gly had no impact. ApoC-II and apoC-III isoforms differed by the oxidation of the two methionine residues in these proteins. Whereas in apoC-II both methionine residues were oxidized in parallel, in apoC-III the two methionine residues differed in their susceptibility towards oxidation. We conclude that the formation of MetSO depends on the molecular microenvironment within a protein.
During the past 20 years 17 patients with abdominal-aortic-intestinal fistulas have been operated in our department. Hospital-letality accounted till 1986 with 75%. Since then we preferred direct reconstruction by implantation of a vascular graft, covered by omentum in primary fistulas. Hospital letality could be reduced by this management to 0% in primary fistulas by a total survival rate of 67%.
In an experimental study on sheeps a new biologic vascular graft was implanted, 30 x in carotidal, 30 x in aortal position. Only one early occlusion of the graft, due to technical reasons, could be observed. Without aneurysmatic degeneration all graft were in function at the time of harvesting the samples. Morphologically a "revitalisation" of the grafts could be proved.