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Biomedical subjects

W Schmitt

Publications and source records attributed to W Schmitt.

At least 37 records · Page 2Linked to original sources

[Schoenlein-Henoch purpura with intestinal involvement].

A 51-year-old male patient admitted to the hospital because of colic-like abdominal pain, paralytic ileus, anal bleeding and microhaematuria with proteinuria, developed an intestinal ischemia with a serum lactate level of 6.3 mmol/l. An occlusion of the large vessels was excluded angiographically. Perfusion disorders were detected both endoscopically and histologically in the upper gastrointestinal tract and in the terminal ileum. When after two days a palpable purpura appeared on the anterior of both feet, a vasculitis type Schoenlein-Henoch was suspected and treated with high doses of steroids, resulting in decreasing symptoms. From the point of admittance, a nephritic urinary sediment had been apparent, and the renal affliction developed into a nephrotic syndrome without notable reduction in the glomerular filtration rate. On the 13th day of treatment the patient-being on a reduced dose of steroids-suffered from a severe relapse; however, this responded favorably to an increase of the dosage. The kidneys required approximately one year for complete recovery. Based on this case, the Schoenlein-Henoch purpura syndrome and its differential diagnosis are presented, particularly with respect to gastrointestinal symptoms and in view of the pertinent literature.

Abdomen↗

Polymorphisms in the tumor necrosis factor genes in Wegener's granulomatosis.

Two known di-allelic polymorphisms in the tumor necrosis factor (TNF) genes were investigated in 35 patients suffering from Wegener's granulomatosis (WG) in comparison to 111 healthy controls. The first polymorphism lay in the promotor region of the TNF-alpha gene at position -308, the second in the first intron of the TNF-beta gene. For both polymorphisms we could not find any statistically significant differences in allele frequencies between patients and healthy individuals. In the patient group the TNF 2/2 phenotype was slightly elevated, however (WG 5.7% vs. normal 1.8%). Investigating the clinical course of the disease according to TNF polymorphisms, TNF 1/1 patients were found to have a higher mean disease extension index (DEI) than TNF 1/2 individuals (TNF 1/1 10.5 vs. TNF 1/2 9.4).

Granulomatosis with Polyangiitis↗

[Pancreaticoscopy: experiences, possibilities and limits].

Cholangioscopy in the mother-baby technique is well accepted and widespread these days. On the other hand, the peroral pancreaticoscopy (POPS) is still in the initial phase of development. In cases of doubtful stenoses, duct discontinuation, and radiolucent shadows during an endoscopic retrograde cholangiopancreatography (ERCP) the POPS can be carried out as a clarifying examination. Two variations of babyscopes are currently available. The ultra-thin endoscope allows only limited results due to the lack of tip control and irrigation. On the other hand, devices with an outer diameter of 3.2 mm and larger provide for a sufficient assessment of the duct mucosa. Biopsies can be taken through the working channel, and the probes for intracorporeal shock wave lithotripsy (ISWL) can be placed under visual control. We performed POPS on 9 patients with an average age of 60 years using a tip-controlled endoscope. In 8 of these cases a diagnostic or therapeutic advantage was gained. A 29-year old patient with alcohol-induced chronic pancreatitis and an occluding duct stone underwent electrohydraulic lithotrips (EHL). A 60-year-old patient with pancreatic duct stones underwent laser-induced shock wave lithotripsy (LISL) in 2 sessions. Afterwards remaining parts of the calculi were extracted. The importance of this method in diagnosis and therapy of pancreatic diseases remains to be established, as evaluation studies of any great extent are still to be done.

Adult↗

Pretreatment but not posttreatment with GYKI 52466 reduces functional deficits and neuronal damage after global ischemia in rats.

Glutamate antagonists have been shown to be neuroprotective in animal models of cerebral ischemia. Global cerebral ischemia in rats leads to selective neuronal damage in the hippocampus and striatum. Following ischemia a deficit in spatial learning and memory occurs. The aim of the present study was to investigate the potential neuroprotective effect of GYKI 52466, an antagonist at the non-N-methyl-D-aspartate receptor, with behavioural and histological measures of global ischemia in rats. Global ischemia was induced by four-vessel-occlusion (4VO) for 20 min in rats. GYKI 52466 (30 mg/kg i.p.) was administered either 20 min before induction of ischemia or immediately after onset of reperfusion. One week after surgery spatial learning was tested in the Morris water maze. After behavioural testing the animals were sacrificed and the neuronal damaged was assessed. GYKI 52466 reduced the increase in escape latency and in swim distance induced by 4VO when given before ischemia but not when applied after ischemia. Neuronal damage in the CA1 sector of the hippocampus produced by 4VO was significantly attenuated by pretreatment but not by posttreatment with GYKI 52466. Striatal neuronal damage was not affected by either treatment with GYKI 52466. GYKI 52466 had neuroprotective effects in a rat model of global cerebral ischemia. Pretreatment with GYKI 52466 protected rats against behavioural deficits and hippocampal neuronal damage induced by 4VO.

Animals↗

An improved TnMax mini-transposon system suitable for sequencing, shuttle mutagenesis and gene fusions.

A new collection of mini-transposons (mini-Tn) of the previously described TnMax series [Haas et al, Gene 130 (1993a) 23-31] has been constructed. The transposons (Tn) bear genes conferring resistance to either chloramphenicol (Cm) or kanamycin (Km). Each member of the new series (TnMax5-TnMax11) contains the general M13 forward (M13-FP) and reverse (M13-RP1) sequencing primers close to the inverted repeats (IR), facilitating the rapid and convenient determination of the DNA sequences flanking the transposon insertion site. Furthermore, the mini-Tn possess the infrequently occurring NotI sites, allowing the localization of genes on macro-restriction maps of bacterial species. Some derivatives contain promoterless trp-lacZ (TnMax11), xylE (TnMax10), phoA (TnMax6) or blaM (TnMax7, TnMax9) genes next to the IR, suitable for the generation of in vivo gene- and operon fusions to study gene regulation, protein export, or to determine the topology of proteins in bacterial membranes. A set of conjugative minimal plasmid vectors (pMin1, pMin2) are used to select for TnMax insertions into the cloned insert, rather than the vector sequences. Due to the small size of the mini-Tn, and a simple and efficient mutagenesis procedure, the TnMax system is a useful tool for targeting and sequencing of cloned genes in Escherichia coli, and especially for shuttle mutagenesis of bacterial species which cannot be targeted by direct transposition.

Base Sequence↗

The antioxidant LY 231617 ameliorates functional and morphological sequelae induced by global ischemia in rats.

In this study the effect of LY 231617, an antioxidant, on spatial learning deficit and on neuronal damage following transient cerebral ischemia was evaluated. Global ischemia was induced by four-vessel-occlusion (4VO) for 20 min in rats. LY 231617 (20 mg/kg i.p.) was administered after onset of reperfusion. One week after surgery spatial learning was tested in the Morris water maze. LY 231617 reduced the increase in escape latency and in swim distance induced by 4VO. Neuronal damage in the CAI sector of the hippocampus produced by 4VO was significantly attenuated by LY 231617. The present data demonstrate that posttreatment with LY 231617 exerts a protective effect on hippocampal neuronal damage and deficits in spatial learning induced by 4VO.

Animals↗

Cloning of the Helicobacter pylori recA gene and functional characterization of its product.

The RecA protein is a key enzyme involved in DNA recombination in bacteria. Using a polymerase chain reaction (PCR) amplification we cloned a recA homolog from Helicobacter pylori. The gene revealed an open reading frame (ORF) encoding a putative protein of 37.6 kDa showing closest homology to the Campylobacter jejuni RecA (75.5% identity). A putative ribosome binding site and a near-consensus sigma 70 promoter sequence was found upstream of recA. A second ORF, encoding a putative protein with N-terminal sequence homology to prokaryotic and eukaryotic enolases, is located directly downstream of recA. Compared to the wild-type strains, isogenic H. pylori recA deletion mutants of strains 69A and NCTC11637 displayed increased sensitivity to ultraviolet light and abolished general homologous recombination. The recombinant H. pylori RecA protein produced in Escherichia coli strain GC6 (recA-) was 38 kDa in size but inactive in DNA repair, whereas the corresponding protein in H. pylori 69A migrated at the greater apparent molecular weight of approx. 40 kDa in SDS-polyacrylamide gels. However, complementation of the H. pylori mutant using the cloned recA gene on a shuttle vector resulted in a RecA protein of the original size and fully restored the general functions of the enzyme. These data can be best explained by a modification of RecA in H. pylori which is crucial for its function. The potential modification seems not to occur when the protein is produced in E. coli, giving rise to a smaller but inactive protein.

Amino Acid Sequence↗

[Multicenter prospective study of the current status of treatment for bleeding ulcer in Germany].

The current state of ulcer treatment in Germany was analysed in a prospective multi-centre study. It was based on 1139 consecutive patients admitted to the participating hospitals because of upper gastrointestinal bleeding. The source of the bleeding was identified by diagnostic endoscopy in 1075 patients (94%), from a gastric and/or duodenal ulcer in 546 of them (mean age 62 +/- 18 years). Using Forrest's classification, 4% of patients were in bleeding stage Ia, 17% in stage Ib, 16% stage IIa, 30% stage IIb and 33% stage III. An attempt to arrest bleeding through the endoscope was made in 233 patients (43%): more often with tissue-preserving substances (epinephrine +/- NaCl in 36%, fibrin glue +/- epinephrine in 24%) than with tissue-damaging procedures (epinephrine + polidocanol +/- NaCl in 26%, epinephrine + thermocoagulation in 7%). Primary haemostasis was achieved in 219 patients (94%). There was a total of 66 recurrences of bleeding (12%), but the rate was 18% after endoscopic haemostasis. 64 patients (12%) required operative intervention, including initial emergency operations. Severe complications (infections, organic failure) occurred in 82 patients (16%). 114 of the 546 patients were in the high risk group (older than 60 years; high amount of bleeding). Their bleeding recurrence and mortality rates (27 and 22%, respectively) were significantly higher (P < 0.01) than those of the total group. Overall mortality rate was 11% (58 patients). The mortality rate depended on the severity of initial bleeding (26% for Forrest group Ia). After recurrent bleeding the mortality rate was 34% with conservative and 33% with operative treatment. 7% of all deaths were the direct result of bleeding. The following factors prognostically closely correlated with mortality rate: age of patient (P < 0.01); haemoglobin < 8 g/dl on admission (P < 0.05); initial severity of bleeding (Forrest group I; P < 0.05); and recurrence of bleeding (P < 0.001).

Age Factors↗

Double-blind trial of omeprazole and amoxicillin to cure Helicobacter pylori infection in patients with duodenal ulcers.

BACKGROUND/AIMS: Anti-Helicobacter pylori treatment with combinations of omeprazole and amoxicillin is a promising treatment option. The aim of this study was to investigate whether a daily omeprazole dose of 120 mg combined with amoxicillin would cure H. pylori infection at a rate comparable with that achieved with "triple therapy." METHODS: In a double-blind, randomized, controlled, and multicenter trial in Germany, 270 patients with an H. pylori-associated duodenal ulcer were treated with 40 mg omeprazole three times a day and 750 mg amoxicillin three times a day for the first 14 days (n = 139) followed by 20 mg omeprazole once daily until day 42 or with omeprazole plus 750 mg amoxicillin placebo three times a day for the same time period (n = 131). RESULTS: Cure rates of H. pylori infection were 91% in the omeprazole plus amoxicillin group, 0% in the omeprazole plus placebo group, and 89% and 0%, respectively, performing an intention-to-treat analysis. Cure of H. pylori infection in patients pretreated with omeprazole was only 58% compared with 95% in patients who were not. The cumulative 12-month relapse rates were 11.3% and 44% in the treatment groups and 1.6% in H. pylori-negative and 49% in H. pylori-positive patients. CONCLUSIONS: The combination of 120 mg omeprazole daily and 2.25 g amoxicillin daily with its H. pylori cure rate of around 90% is one of the best tolerated and most effective treatment regimens.

Adolescent↗

[Effect of nilvadipine on nifedipine-induced edema of the lower leg. Results of a double-blind randomized comparative study].

OBJECTIVE: Evaluation of the effects of nilvadipine on nifedipine-induced lower-leg edema. STUDY DESIGN: multicenter, randomized, double-blind study. PATIENTS: 61 outpatients suffering from essential hypertension with diastolic blood pressure adjusted to < or = 95 mmHg by nifedipine, and simultaneous lower-leg edema. MEDICATION: First phase: wash-out--placebo b.i.d.; Second phase: slow-release nifedipine 20 mg b.i.d.; Third phase: slow-release nifedipine 20 mg b.i.d. or nilvadipine 8 mg (mornings) and placebo (evenings). PARAMETERS: Lower leg volume, blood pressure, heart rate, weight, laboratory investigations, undesired effects, assessment of effectiveness and tolerability by the physician, subjective patient assessment. RESULTS: Patients treated with nilvadipine immediately following nifedipine therapy showed a significant decrease in lower-leg volume as compared with those continuing to receive nifedipine. In about half of the patients receiving nilvadipine, nifedipine-induced lower-leg edema disappeared completely. No differences were seen between the two substances in terms of effectiveness or tolerability.

Aged↗

[Angioimmunoblastic lymphadenopathy with dysproteinemia and sclerosing cholangitis].

A 28-year-old man with recurrent swelling of both upper eyelids was found to have increased values in several liver function tests (GOT 162 U/l, GPT 356 U/l, gamma-GT 643 U/l, bilirubin 3.0 mg/dl, alkaline phosphatase 925 U/l). Abdominal ultrasonography demonstrated lymph node enlargements up to 3 cm, dilated intra- and extrahepatic bile ducts, as well as a cyst of 3 cm size in the pancreatic tail. Endoscopic retrograde cholangiopancreatography and punch biopsy of the liver revealed sclerosing cholangitis. In addition to the eyelid swellings the patient also had protrusion of the left eyeball, blood eosinophilia (800/microliter) and marked increase in polyclonal IgG (6930 mg/dl) with lymphadenopathy suggesting the diagnosis of angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD, lymphogranulomatosis X), confirmed by lymphocyte surface marker analysis. However, histological examination of a lymph node was more suggestive of a T-zone lymphoma. Treatment with ursodeoxycholic acid (250 mg three times daily) and prednisolone (initially 2 mg/kg daily) quickly led to normal biochemical values and regression of the eye changes. In addition, treatment with interferon alpha-2b (initially 3 mill. U daily for 10 days) was begun. The abnormalities in the bile ducts disappeared 6 months later. The patient has been in full remission for 25 months (prednisolone dosage reduced to 12.5/7.5 mg alternating daily and interferon alpha-2b 3 mill. U three times weekly). This response makes AILD with secondary involvement of the bile ducts the most likely diagnosis.

Adult↗

Activated neutrophils express proteinase 3 on their plasma membrane in vitro and in vivo.

Apart from the diagnostic value of anti-neutrophil cytoplasmic antibodies (ANCA), their detailed characterization and that of their corresponding antigens have opened new ways for the exploration of the pathogenesis of primary systemic vasculitis. ANCA are now thought to play an important functional role via activation of phagocytic cells (e.g. polymorphonuclear neutrophils (PMN)). In this study we examined the mechanisms by which ANCA could gain access to proteinase 3 (PR3) in intact PMN, at two levels: ex vivo by analysing the presence of PR3 on the plasma membrane of PMN from patients with ANCA-associated vasculitis, and in vitro by stimulation of PMN using different cytokines, including recombinant tumour necrosis factor-alpha (rhTNF-alpha) and two forms of IL-8 (produced by monocytic and endothelial cells). Using immunocytochemical staining techniques (FACS and immunoelectronmicroscopy) PR3 has been detected on the plasma membrane of PMN from patients with active ANCA-associated vasculitis. However, this phenomenon is also seen in patients with sepsis who do not have ANCA. In addition, TNF-alpha and both forms of IL-8 act synergistically and induce a translocation of PR3 from the intragranular loci to the cell surface of PMN. These results provide strong evidence for the hypothesis that ANCA are directly pathogenic by binding to PR3 which is expressed on the cell surface of primed/activated PMN.

Antibodies, Antineutrophil Cytoplasmic↗

Genetic analysis of the Helicobacter pylori vacuolating cytotoxin: structural similarities with the IgA protease type of exported protein.

The human gastric bacterial pathogen Helicobacter pylori has been implicated in type B gastritis, peptic ulceration and gastric adenocarcinoma. Here we report on the cloning and genetic characterization of an H. pylori gene named vacA, which encodes the vacuolating cytotoxin VacA, a novel type of antigenic bacterial toxin that induces the formation of intracellular vacuoles in epithelial cells. The vacuolating cytotoxin activity is expressed by a subset of clinical isolates (Vac+), all of which produce the 87 kDa cytotoxin antigen, but strains which produce neither the activity nor the cytotoxin protein (Vac-) also carry the gene. Isogenic H. pylori mutants in vacA generated by transposon shuttle mutagenesis produce neither the VacA antigen nor a vacuolating activity in a cell culture model. The vacA gene itself encodes a precursor protein of 139.6 kDa consisting of a 33-amino acid signal sequence, the 87 kDa cytotoxin and a 50 kDa C-terminal domain with features typical of a bacterial outer membrane protein. The VacA precursor shows no significant primary sequence homology with any previously reported protein, but its structural organization closely resembles the IgA protease-type of exoprotein produced by pathogenic Neisseriae and Haemophilus species. Our current data support a model for secretion of the cytotoxin through the two bacterial membranes which involves the 50 kDa domain for outer membrane translocation with subsequent proteolytic cleavage and release of the mature 87 kDa cytotoxin into the extracellular environment.

Amino Acid Sequence↗

[Not Available].

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Germany↗

[Alpha-heavy chain disease--Mediterranean lymphoma].

For 6 months diarrhea and weight loss of 30 kg occurred in a 28 year old man from the Emirates. The endoscopic examination suggested a small intestinal lymphoma affecting the entire small intestine, which was confirmed by biopsies, immunohistochemistry, immunologic proof of monoclonal IgA-gammopathy in serum and urine. The patient acquired a malignant MALT-lymphoma of B-cell-type, a alpha-Heavy Chain Disease, synonym mediterranean lymphoma or immunoproliferative small intestinal disease (IPSID), stage A with transition in stage B. The patient was treated with ciprofloxacine in association with metronidazole with no influence of the course of the disease.

Adult↗