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Biomedical subjects

M Wimmer

Publications and source records attributed to M Wimmer.

At least 19 recordsLinked to original sources

Orientation of the acetabular component. A comparison of five navigation systems with conventional surgical technique.

We compared the orientation of the acetabular component obtained by a conventional manual technique with that using five different navigation systems. Three surgeons carried out five implantations of an acetabular component with each navigation system, as well as manually, using an anatomical model. The orientation of the acetabular component, including inclination and anteversion, and its position was determined using a co-ordinate measuring machine. The variation of the orientation of the acetabular component was higher in the conventional group compared with the navigated group. One experienced surgeon took significantly less time for the procedure. However, his placement of the component was no better than that of the less experienced surgeons. Significantly better inclination and anteversion (p < 0.001 for both) were obtained using navigation. These parameters were not significantly different between the surgeons when using the conventional technique (p = 0.966). The use of computer navigation helps a surgeon to orientate the acetabular component with less variation regarding inclination and anteversion.

Acetabulum↗

Glutamate-associated plasticity in the ventral tegmental area is necessary for conditioning environmental stimuli with morphine.

We sought to determine if plasticity in the ventral tegmental area (VTA) of the midbrain is involved in learning to associate morphine exposure with a specific environment. For this, we tested whether activation of glutamate receptors and protein kinase A is needed for the acquisition and expression of a morphine-conditioned place preference (CPP). Rats received bilateral microinjections of either the NMDA antagonist AP5 (0.48 nmol/0.3 microl), the AMPA antagonist CNQX (0.21 nmol/0.3 microl), or vehicle into the VTA prior to each of three morphine-conditioning sessions. Both the AMPA and NMDA receptor antagonists blocked the development of morphine CPP when given into the VTA but not when given outside the VTA. In similar studies the protein kinase A (PKA) inhibitor, Rp-cAMPS (13 nmol/0.3 microl), blocked the acquisition of morphine CPP when given into the VTA immediately after morphine conditioning. In separate experiments, glutamate antagonists, or Rp-cAMPS, immediately prior to the preference test blocked the expression of morphine CPP when microinjected into the VTA. These data indicate that the VTA is an important site for synaptic modifications involved in the learning and memory of environmental cues predicting reward, and that glutamate input and PKA activation are crucial to this process.

2-Amino-5-phosphonovalerate↗

Protein tyrosine phosphatase 1B is located with glucagon vesicles, and its concentration is inversely correlated with the rate of glucagon secretion of INR1G9 cells.

High concentrations of protein tyrosine phosphatase (PTP) were found with secretory vesicles of glucagon-producing INR1G9 cells by electron microscopic immunocytochemistry, using a polyclonal antiserum specific for the PTP1B/T-cell (TC)PTP subfamily of PTP. Since TCPTP protein and mRNA were below the detection limit in the cells but significant amounts of PTP1B and mRNA were recognised by a specific monoclonal antibody and a mRNA probe we conclude, that the PTP associated with the vesicles is PTP1B. Only reverse transcriptase (RT)-PCR with primers specific for PTP1B yielded a product of the expected nucleotide sequence. Thus, we conclude that the PTP associated with the vesicles is PTP1B. The presence of vanadate for 48 h attenuated PTP1B expression and caused reduction of steady-state levels of the phosphatase. These conditions also led to a continuing increase in the steady-state rate of glucagon release by the cells. This rate and tyrosine phosphatase levels showed an inverse relationship, suggesting a suppressive role of PTP1B on the regulated secretion of glucagon by INR1G9 cells.

Animals↗

Beta-myosin heavy chain gene mutations and hypertrophic cardiomyopathy in Austrian children.

Hypertrophic cardiomyopathy occurs in two variants, either as an autosomal dominant familial disorder or as a sporadic disease without familial involvement. Different genes coding sarcomeric proteins of the heart have been identified as causing hypertrophic cardiomyopathy. Missense mutations in the cardiac beta-myosin heavy chain gene are found in 30% of all cases of familial hypertrophic cardiomyopathy. We screened the beta-myosin heavy chain gene of children of nine Austrian families with hypertrophic cardiomyopathy (referred to as group A) and of seven children with sporadic hypertrophic cardiomyopathy (referred to as group B). We were able to find two previously described (V606M, R453C) and two unknown missense mutations (V406M, R663H) in group A. Additionally, in two children of group B we could identify one already known missense mutation, R249Q as well as one previously unknown missense mutation, M877K. The genetically affected children of group A developed no or only mild clinical symptoms, whereas the children of group B with genetically confirmed sporadic hypertrophic cardiomyopathy showed manifest left ventricular hypertrophy and clinical symptoms including chest pain and dyspnoea. Clinical symptoms among the adults of group A, suffering from familial hypertrophic cardiomyopathy, varied significantly. We therefore believe V406M to be a more malignant missense mutation, probably linked with sudden death in the affected family, than R663H, which seems to be more benign causing late-onset hypertrophic cardiomyopathy and mild clinical symptoms in the affected family members.

Adolescent↗

[Comparison of the annual data of 2 stroke units in neurological clinics of acute hospitals].

The Stroke Unit concept of the German Neurological Society differs from its precedents in Scandinavia or the United Kingdom. Hallmarks of the German concept are very early onset of diagnosis and treatment, continuous surveillance of vital functions by bedside monitors and specialized care by a multiprofessional team. This comparison of two Stroke Units in Minden and Munich-Harlaching, working according to the new German concept, shows broad similarities in admission intervals, diagnostic procedures, treatment modalities and short term prognosis, with an exceedingly low in-hospital mortality of 3.4-5.6% and a high proportion of patients (64-69%) leaving the hospital with Barthel scores above 70. Ongoing studies will show how this kind of Stroke Unit treatment compares to general wards.

Aged↗

In vitro activities of linezolid alone and in combination with amoxicillin, clarithromycin, and metronidazole against Helicobacter pylori.

Linezolid was tested against 70 strains of Helicobacter pylori by the agar dilution method. The MIC range and MICs at which 50 and 90% of strains were inhibited were 8 to 64, 16, and 32 microgram/ml, respectively. With minimum and maximum fractional inhibitory concentration summation values of 0.31 and 2.50, respectively, the combination of linezolid with amoxicillin, clarithromycin, or metronidazole showed either partial synergy or indifference for the majority of strains.

Acetamides↗

A non-receptor-type protein phosphotyrosine phosphatase is enriched in secretory vesicles of glucagon - and pancreatic polypeptide - secreting cells of the endocrine pancreas.

The secretory vesicles of some cells of the islets of Langerhans of the pancreas contain high amounts of immunoreactive tyrosine phosphatase of the PTP1B/TCPTP subfamily. The cells are located in the peripheral parts of the islets and were identified as glucagon- and pancreatic polypeptide-forming cells. The tyrosine phosphatase is also enriched in some of the somatostatin-producing cells but is not elevated either in insulin-producing B-cells or in the exocrine pancreas. Virtually the same patterns were found in pancretic tissues of rats, guinea pigs, pigs, and mice. High levels of detergent-soluble tyrosine phosphatase were measured in the particular fraction of pancreatic islets with a substrate preferred by PTP1B/TCPTP-type protein tyrosine phosphatases.

Animals↗

Nemaline myopathy and cardiomyopathy.

A case report is presented in which a 4-year-old male is diagnosed with hypertrophic cardiomyopathy, respiratory distress, muscle hypotonia, and psychomotor retardation. Electron microscopic study of skeletal muscle biopsy revealed pathologic changes typical of congenital nemaline myopathy, and biochemical analysis revealed a disorder of mitochondrial fatty acid oxidation. Therefore a previously undescribed combination of a structural and metabolic myopathy is reported.

Acyl-CoA Dehydrogenase↗

Famotidine versus omeprazole in combination with clarithromycin and metronidazole for eradication of Helicobacter pylori--a randomized, controlled trial.

BACKGROUND: One-week low-dose triple therapy is currently considered the gold standard regimen for treatment of Helicobacter pylori infection. However, the mechanisms involved in the synergy between antibiotics and proton pump inhibitors are controversial. AIMS: To test the hypothesis that acid suppression represents the crucial mechanism by which the antibacterial activity of antibiotics can be enhanced, and to assess the impact of primary resistance on treatment outcome. METHODS: One hundred and twenty patients with H. pylori infection and duodenal ulcer, gastric ulcer or non-ulcer dyspepsia were randomly assigned to a 1 week course of either famotidine 80 mg b.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (FCM group; n = 60) or omeprazole 20 mg o.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (OCM group; n = 60). Gastroscopy was performed at baseline and 5 weeks after completion of treatment. H. pylori status was assessed by biopsy urease test, histology and culture. RESULTS: In the intention-to-treat analysis, eradication of H. pylori was achieved in 47 of 60 patients (78%; 95% CI: 66-88%) in the FCM group, compared to 44 of 60 patients (73%; 95% CI: 60-84%) in the OCM group (N.S.). Using per protocol analysis, eradication therapy was successful in 47 of 52 patients (90%; 95% CI: 79-97%) treated with FCM and 44 of 57 patients (77%; 95% CI: 64-87%) treated with OCM (N.S.). Primary metronidazole resistance was present in 27% and primary clarithromycin resistance in 8% of strains. Overall per protocol eradication rates in strains susceptible to both antibiotics and strains with isolated metronidazole resistance were 93% and 84%, respectively. No patient with clarithromycin resistance responded to treatment. CONCLUSIONS: High-dose famotidine and omeprazole, combined with clarithromycin and metronidazole, are equally effective for eradication of H. pylori. In 1-week low-dose triple therapy, metronidazole resistance has no major impact on eradication rates whereas clarithromycin resistance is associated with a poor treatment outcome.

Adult↗

IgG subclass reactivity to human cardiac myosin in cardiomyopathy patients is indicative of a Th1-like autoimmune disease.

Studies performed in mice together with the demonstration of increased levels of heart-specific autoantibodies, cytokines and cytokine receptors in sera from cardiomyopathy (CMP) patients argued for a pathogenic role of autoimmune mechanisms in CMP. This study was designed to analyse the presence of IgG anti-heart antibodies in sera from patients suffering from hypertrophic and dilatative forms of CMP as well as from patients with ischaemic heart disease and healthy individuals. Patients' sera were analysed for IgG reactivity to Western-blotted extracts prepared from human epithelial and endothelial cells, heart and skeletal muscle specimens as well as from Streptococcus pyogenes. The IgG subclass (IgG1-4) reactivity to purified human cardiac myosin was analysed by ELISA. While sera from CMP patients and healthy individuals displayed comparable IgG reactivity to a variety of human proteins, cardiac myosin represented the prominent antigen detected strongly and preferentially by sera from CMP patients. Pronounced IgG anti-cardiac myosin reactivity was frequently found in sera from patients with dilatative CMP and reduced ventricular function. ELISA analyses revealed a prominent IgG2/IgG3 anti-cardiac myosin reactivity in CMP sera, indicating a preferential Th1-like immune response. Elevated anti-cytomegalovirus, anti-enterovirus IgG titres as well as IgG reactivity to nitrocellulose-blotted S. pyogenes proteins were also frequently observed in the group of CMP patients. If further work can support the hypothesis that autoreactivity to cardiac myosin represents a pathogenic factor in CMP, specific immunomodulation of this Th1- towards a Th2-like immune response may represent a promising therapeutic strategy for CMP.

Adolescent↗

Pediatric cardiac extracorporeal membrane oxygenation in congenital heart disease: the cardiologist's view.

There is no doubt that extracorporeal membrane oxygenation (ECMO) as a powerful therapeutic modality in critically ill newborn infants and older children with congenital heart disease has implications for the pediatric cardiologist. His responsibilities as consultant in the intensive care unit include screening for unsuspected cyanotic heart disease in neonatal candidates referred for ECMO and appraisal of surgical repair in postcardiotomy patients as well as assessment of postoperative hemodynamics and detection of complications during perfusion. A close cooperation between intensive care specialists and other appropriate specialists (pediatric cardiologists, cardiac surgeons, and anesthesiologists) is required for the process of decision making prior to initiation of postoperative ECMO in the individual patient with congenital heart disease. Long-term survival, morbidity, cerebrovascular complications, and neurodevelopmental sequelae of these near miss children remain a critical issue. Furthermore, there is a strong need for professional psychosocial support of affected parents, both in the hospital and after discharge.

Brain Diseases↗

Extracorporeal life support in pediatric patients with heart failure.

The prognosis of patients with end-stage heart failure presenting with acute clinical deterioration is poor. Extracorporeal membrane oxygenation (ECMO), however, can provide univentricular and biventricular cardiac support which has led to the extended application of ECMO to infants and children. With improving results, indications and modalities of mechanical support have changed, and mechanical bridge to cardiac transplantation will offer extended survival for selected patients. The purpose of this article is to provide comprehensive data of pediatric cardiac support and to discuss the central role of echocardiography in the estimation of cardiac performance during mechanical support. As a conclusion, one can predict that the encouraging results of today will lead to further technological developments, which will create individual technical solutions of different clinical applications.

Cardiomyopathies↗

[Clinical diagnosis and stroke subtypes].

Sudden focal neurological symptoms are caused by stroke in 95%, either ischemic or hemorrhagic. Diagnosis and onset of treatment has to be rapid because the tolerance of the brain tissue to ischemia is lower than in any other tissue. First priority has stabilization of vital parameters such as maintenance of high blood pressure, rehydration, oxygen supply and correction of hyper-/hypoglycemia. Of equal importance is the prompt imaging of the brain to differentiate bleeding, complete brain infarction and early ischemic signs--only the latter permitting recanalization procedures by thrombolysis in a narrow time window of three hours. Distinct etiological diagnosis by Duplex scanning and echocardiography usually follows. This information determines the stroke subtype and the choice of secondary prevention measures.

Brain Ischemia↗

Ascaris suum: protein phosphotyrosine phosphatases in oocytes and developing stages.

Protein tyrosine phosphatases were analyzed in oocytes of Ascaris suum. Phosphatases dephosphorylating modified acidic lysozyme were present in high-molecular-weight form (M(r) > 600,000) and as a 50- to 55-kDa protein in the soluble fraction. The low-molecular-weight form of the phosphatase cross-reacted with an antiserum raised against human T-cell protein tyrosine phosphatase and was not distinguishable from the 50- to 55-kDa protein tyrosine phosphatase previously described in the muscular layer of the adult worms (B. Schmid et al. 1996, Molecular and Biochemical Parasitology 77, 183-192). The low-molecular-weight form was also present on immunoblots of high-molecular-weight protein tyrosine phosphatase preparations after denaturing electrophoresis. The same or a similar form of the tyrosine phosphatase was also found in detergent extracts from the pelletal fraction. In addition, another tyrosine phosphatase of 180 kDa molecular mass that dephosphorylated myelin basic protein was also found in extracts from the soluble compartment as well as in detergent extracts from the pelletal fraction. It showed no cross-reactivity with antisera raised against soluble mammalian phosphatases and was resistant to inhibition by vanadate. While the activities of the myelin basic protein-dephosphorylating protein phosphatase remained fairly constant during early development of the oocytes, the activity of the enzyme dephosphorylating modified lysozyme in the pelletal fraction decreased to less than 10% of the initial activity between days 3 and 28 of incubation. Immunocytochemical studies of unfertilized and developing Ascaris eggs revealed association of protein tyrosine kinase and protein tyrosine phosphatase with the egg shell, in addition to their presence in the neighborhood of mitochondria. The amount of enzyme changed with the stage of development. In the larval stage (21 days) protein tyrosine kinase had increased in the chitin layer of the shell and in the nuclei while the relative amount of tyrosine phosphatase decreased in accordance with the biochemical data.

Animals↗

Detection of Helicobacter pylori in stool specimens by PCR and antigen enzyme immunoassay.

A highly sensitive seminested PCR assay to detect Helicobacter pylori DNA in feces was developed. PCR with stool specimens and a novel antigen enzyme immunoassay (EIA) for H. pylori detection in feces were evaluated as diagnostic tools and in follow-up with samples from 63 infected and 37 noninfected persons. Infected individuals received eradication therapy followed by endoscopic follow-up 35 days after the start of treatment. At that time, a second stool specimen was obtained from 55 of these patients. Before eradication, the sensitivity of PCR was 93.7% and that of EIA 88.9%. Specificities were 100 and 94.6%, respectively. Of the 55 follow-up specimens, 41 originated from patients from whom H. pylori had been eradicated. Of these, 21 were still positive by PCR and 13 were positive by EIA, indicating that 1 month may be too short a period for follow-up evaluation of stool specimens by these tests.

Adult↗

[Aortic coarctation--long-term follow-up in adults].

Surgical repair of coarctation of the aorta has been performed since 1945. Although surgical techniques have improved, problems such as restenosis and aneurysm at the operation site or hypertensive cardiovascular disease, still remain. To evaluate the long-term results after surgical repair of coarctation, 41 patients, 25 male and 16 female patients (mean age: 28 +/- 11 years, range 14-57 years), were studied 16 +/- 8 years after surgery (range 3-44 years). Mean age at surgery was 12 +/- 9 years (range 0.5-35 years). In 24 patients resection and end-to-end anastomosis had been performed, patch graft aortoplasty in nine patients, tube interposition graft in seven patients and one patient had undergone the subclavian flap technique. All patients were assessed by exact physical examination, the resting arm-to-leg systolic pressure gradient was measured by Doppler sonography, a bicycle exercise test and an echocardiogram were performed. Twenty-one patients reported postoperative symptoms such as dizziness (n = 12), headache (n = 3), cold legs (n = 10) and/or dyspnea (n = 8). In two patients the resting arm-to-leg pressure gradient was greater than 30 mm Hg, in two patients it was greater than 20 mm Hg. Gradient calculated by Doppler echocardiography ranged from 0 to 80 mm Hg (21 +/- 17 mm Hg) and showed poor correlation with the arm-to-leg pressure difference. The mean functional capacity was 89 +/- 18% (range 42-110%). In 18 patients exercise-induced hypertension was found, while in only eight patients arterial hypertension had already been known. To evaluate the morphology of the aorta MRI was performed in 28 patients. No aneurysm was found. In five patients a minimal lumen diameter as small as 9-11 mm was measured. Patients were divided into two groups according to their age at operation, group I: < 9 years (n = 19) and group II: > 9 years (n = 22). Resting blood pressure was significantly higher in group II (135 +/- 27 mm Hg vs 114 +/- 20 mm Hg, p < 0.009), anti-hypertensive medication (43% vs 11%, p < 0.04) and symptoms were more frequent in these patients (15/22 vs 6/19, p < 0.04). However at time of follow-up examination the age of patients of group II was significantly higher (33 +/- 12 vs 22 +/- 5 years, p < 0.0005). Between these two groups there was no difference in follow-up time and results of echocardiography or stress test. In conclusion, despite good long-term results after surgical repair of coarctation of the aorta, patients should be followed on a regular basis primarily in order to recognize systemic hypertension as early as possible and to improve the long-term outcome in these patients by antihypertensive treatment.

Adolescent↗

Myoadenylate deaminase deficiency, hypertrophic cardiomyopathy and gigantism syndrome.

We report a 20-year-old man with gigantism syndrome, hypertrophic cardiomyopathy, muscle weakness, exercise intolerance, and severe psychomotor retardation since childhood. Histochemical and biochemical analysis of skeletal muscle biopsy revealed myoadenylate deaminase deficiency; molecular genetic analysis confirmed the diagnosis of primary (inherited) myoadenylate deaminase deficiency. Plasma, urine, and muscle carnitine concentrations were reduced. L-Carnitine treatment led to gradual improvement in exercise tolerance and cognitive performance; plasma and tissue carnitine levels returned to normal, and echocardiographic evidence of left ventricular hypertrophy disappeared. The combination of inherited myoadenylate deaminase deficiency, gigantism syndrome and carnitine deficiency has not previously been described.

AMP Deaminase↗