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J Winkler

Publications and source records attributed to J Winkler.

At least 37 records · Page 2Linked to original sources
PubMed2004

[Correlation of TEI Index and invasive parameters of rightheart function in PAH].

BACKGROUND: The reduction of right ventricular function characterizes patients with severe pulmonary hypertension (PAH). Monitoring right ventricular function therefore is important. Echocardiography is the method of choice for this purpose. The so called Tei-Index seems to be an adequate diagnostic tool with prognostic relevance. We here compared Tei-Index with parameters of right heart catheterization in patients with PAH. PATIENTS AND METHODS: Tei-Index was calculated in 42 patients from the sum of isovolumetric contraction time and relaxation time divided by ejection time. A right heart catheter was performed the same day and pulmonary arterial mean pressure (PAPm) as well as pulmonary arterial resistance (PAR), central venous saturation (SVO (2)), central venous pressure (ZVD) stroke volume (SV) and right ventricular ejection fraction (RVEF) were recorded. RESULTS: Correlation were observed between in each case Tei-Index and RVEF (r = - 0.72; p < 0.001), SV (r = - 0.52; p < 0.001), ZVD (r = 0.65; p < 0.001) and SVO (2) (r = - 0.58; p < 0.001). Tei-index did not correlate with PAPm and PAR. CONCLUSION: Correlations of Tei-Index with parameters of right ventricular function derived from right heart catheterization support the usefulness of 2D-doppler echocardiography for monitoring right heart function in PAH patients.

Blood Pressure↗
PubMed2004

Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial hypertension.

It has been proposed that targeted treatments should be combined for patients with idiopathic pulmonary arterial hypertension (IPAH) responding insufficiently to monotherapy. This study followed the clinical course of nine patients with severe IPAH, in whom the endothelin receptor antagonist bosentan caused transient clinical improvement, eventually followed by a decline in exercise tolerance, who received adjunct treatment with the phospodiesterase-5-inhibitor sildenafil. Measurements included the 6-min walk distance (6MWD) and cardiopulmonary exercise testing (CPET). The 6MWD at baseline was 346+/-66 m and improved to 403+/-80 m 3 months after introduction of bosentan treatment. However, this effect was not sustained and, after an interval of 11+/-5 months, the walk distance had declined to 277+/-80 m. At this point, sildenafil was added to bosentan. Three months later, the 6MWD had increased to 392+/-61 m and the patients remained stable throughout the median follow-up of 9 months (range 6-12). Measurement of the maximum oxygen uptake during CPET confirmed these results. The combination of bosentan and sildenafil was well tolerated by all patients. These preliminary data suggest that combining bosentan and sildenafil may be safe and effective in patients with idiopathic pulmonary arterial hypertension.

Adult↗
PubMed2004

Population pharmacokinetics of methylprednisolone in accident victims with spinal cord injury.

OBJECTIVE: High-dose methylprednisolone (MP) is used to treat acute spinal cord injury (ASCI). The objective of the present study was to determine the pharmacokinetics of the pro-drug methylprednisolone hemisuccinate (MPHS) and MP in accident victims with ASCI. METHODS: The patients (n = 26) were treated with a bolus intravenous loading dose of 30 mg/kg MPHS within 2 h after injury and this was followed by a maintenance infusion of 5.4 mg/kg/h up to 24 h. Blood, CSF and saliva samples were collected up to 48 h after the initial dose and the samples were analyzed by HPLC. Concentration-time data of MPHS and MP were analyzed using population pharmacokinetic analysis with NONMEM software. RESULTS: MPHS and MP could be monitored in plasma and CSF. MP but not MPHS was present in saliva. High variability was seen in the MPHS levels in CSF. The pharmacokinetics of the pro-drug and the metabolite were adequately described by a 2-compartment model with exponential distribution models assigned to the interindividual and the residual variability. At steady state, the average measured MP concentration in plasma was 12.3+/-7.0 microg/ml and 1.74+/-0.85 microg/ml in CSF. The CSF levels of MP could be modeled as a part of the peripheral compartment. CONCLUSION: This study demonstrated that CSF concentrations of MP were sufficiently high after i.v. administration and reflected the concentrations of unbound drug in plasma. Salivary levels of MP were about 32% of the plasma level and may serve as an easily accessible body fluid for drug level monitoring.

Accidents↗
PubMed2004

Clinical spectrum of muscle-eye-brain disease: from the typical presentation to severe autistic features.

Muscle-eye-brain disease (MEB) is an autosomal recessive congenital muscular dystrophy with ocular abnormalities and type II lissencephaly. MEB is caused by mutations in the protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase (POMGnT1) gene on chromosome 1q33. POMGnT1 is a glycosylation enzyme that participates in the synthesis of O-mannosyl glycan. The disease is characterized by altered glycosylation of alpha-dystroglycan. The clinical spectrum of MEB phenotype and POMGnT1 mutations are significantly expanded. We would like to present two cases with MEB disease with POMGnT1 mutations, whose clinical picture shows heterogeneity. The patient with R442H mutation had the classical form of the disease although the one with IVS17-2A-->G homozygous mutation had severe autistic features as the dominating presenting sign. These two cases represent different spectrums of one disorder. To the best of our knowledge, autistic features and stereotypical movements have not been included thus far as a part of broad and heterogeneous MEB spectrum.

Adolescent↗
PubMed2003

"Motor circuit" gray matter changes in idiopathic cervical dystonia.

BACKGROUND: Idiopathic cervical dystonia (ICD), the most common adult-onset focal dystonia, is clinically characterized by involuntary uni- or bilateral contractions of head and neck musculature. One crucial criterion for the diagnosis of ICD is normal results on MRI of the brain. OBJECTIVE: To test the hypothesis whether subtle brain structure changes occur in ICD. METHODS: Using voxel-based morphometry, the authors compared the brain structure of 10 patients with ICD with that of 10 healthy sex- and age-matched controls using high-resolution MRI. RESULTS: Patients with ICD showed an increase in gray matter density bilaterally in the motor cortex and in the cerebellar flocculus and unilaterally in the right globus pallidus internus. In addition, a decrease in gray matter density was observed in the right caudal supplementary motor area as well as in the right dorsal lateral prefrontal and visual cortex. CONCLUSIONS: These results demonstrate for the first time in vivo subtle morphologic alterations in ICD. These data challenge the principal concept that patients with ICD have no brain structure abnormalities and that this movement disorder is solely due to abnormal cerebral function.

Adult↗
PubMed2003

ARX mutations in X-linked lissencephaly with abnormal genitalia.

X-linked lissencephaly with abnormal genitalia (XLAG) is a distinct form of lissencephaly associated with absent corpus callosum. Recently, forms of syndromic and nonspecific X-linked mental retardation have been found to be associated with mutations in the Aristaless-related homeobox gene ARX. The authors assessed ARX as a candidate gene for XLAG in a genetic analysis of neuronal migration disorders and found two different point mutations in two XLAG pedigrees affecting the homeodomain of the protein, confirming that ARX is a causative gene for XLAG.

Abnormalities, Multiple↗
PubMed2003

Molecular genetic investigations in the CCM1 gene in sporadic cerebral cavernomas.

OBJECTIVE: Cerebral cavernous malformations (CCM) occur in familial and sporadic forms that cannot be distinguished by phenotype. Mutations in Krit1, a gene located at the CCM1 locus on chromosome 7q21, account for the majority of familial CCM cases. The authors investigated the role that mutations at the CCM1 locus play in sporadic cavernomas and the prevalence of occult familial forms among symptomatic cavernomas. METHODS: The authors screened the DNA of cavernomas and adjacent normal brain tissue of 72 consecutive patients treated at the Neurosurgical Department/Ludwig-Maximilian University for mutations in Krit1. Eight of the patients had been suspected to have a mutation at CCM1, as they showed multiple cavernomas or clinically familial forms. RESULTS: None of the patients showed a mutation at the CCM1 site, either in cavernomas or in normal brain tissue. CONCLUSION: Mutations in Krit1 are seldom a cause of sporadic cavernomas.

Adolescent↗
PubMed2003

Somatic mosaicism and variable penetrance in doublecortin-associated migration disorders.

X-linked isolated lissencephaly sequence (XLIS) and subcortical band heterotopia (SBH) are allelic disorders caused by mutations in the doublecortin (DCX) gene. This genetic analysis of seven families revealed four novel mutations in the DCX gene. The authors detected a high rate of somatic mosaicism in male and female patients with variable penetrance of bilateral SBH including nonpenetrance in a heterozygous woman. In addition, the authors implemented prenatal diagnosis in a family with SBH/XLIS.

Adult↗
PubMed2003

[Retinal photoablation with the Erbium:YAG laser. Initial experimental results for traction-free removal of tissue].

BACKGROUND: To investigate the potential of an Er:YAG laser for precise and traction-free removal of retinal layers in vitro. MATERIAL AND METHODS: Retinal ablation in porcine retinal explants was performed using a free running Er:YAG laser focused either into a low-OH quartz fiber or a sapphire fiber. The explants were treated under air or perfluorodecaline (PFD). The ablation depth was evaluated by optical coherence tomography (OCT) and histology sections. RESULTS: A radiant exposure of 5.0 J/cm(2) under air and PFD resulted in complete transsection of the neurosensory retina. Between 3.5 and 2.0 J/cm(2) the ablation depth and the defect patterns varied markedly and adjacent thermal zones areas were seen. Below 2.0 J/cm(2) no defects could be created in air, whereas under PFD the ablation extended into the ganglion cell layer. Ablations using a sapphire fiber and 2.0 J/cm(2) showed a significantly higher reproducibility of ablation depth, and homogeneous defect patterns limited to the nerve fiber layer could be produced without thermal damage. CONCLUSIONS: The Er:YAG laser system with a low-OH quartz fiber allowed ablation of inner retinal layers in vitro, but revealed a variable ablation depth and low reproducibility.However, a sapphire fiber showed markedly improved results. Therefore its use during vitreoretinal surgery seems possible not only as a cutting device but also as a tool for the ablation of fine retinal structures.

Animals↗
PubMed2003

[Nosocomial pneumonias in haematological malignancies in the medical intensive care unit].

30 patients with malignant haematological disorders and nosocomial pneumonia, treated during a three-year period in the medical intensive care unit (ICU) of a university hospital, were studied in retrospect. Twelve patients had received bone marrow or peripheral stem cell transplantations 90 +/- 143 (10 - 546) days prior to ICU admission. Six of these received cyclosporin A. 19 of 30 patients were on corticosteroids and 20 had received courses of chemotherapy within a period of one month prior to ICU admission. Patients presented with signs of pulmonary infection and respiratory failure. In 24 patients the likely causative pathogen for pneumonia could be identified. Gram-negative bacteria (n = 17) were in the majority, lead by Pseudomonas, Enterobacter, and Klebsiella species. Gram-positive bacteria (n = 5) were Streptococcus and Staphylococcus species. Infections with Chlamydiae species were diagnosed in two cases. Fungal infections were caused by Candida (n = 8) or Aspergillus species (n = 3) and viral infections by Cytomegalovirus (n = 6). Infections with more than one pathogen were common. Ten patients had pneumonia associated with signs of diffuse pulmonary parenchymal damage of varying degree. 26 patients received mechanical ventilation for 7 +/- 9 (1 - 32) days. The duration of stay in the ICU was 11 +/- 10 (1 - 43) days. 26 of the 30 patients (87 %) died. Patients with haematological malignancies and nosocomial pneumonias have despite medical intensive care treatment a poor prognosis with substantial mortality.

Adult↗
PubMed2002

Different expression of endothelin in the bronchoalveolar lavage in patients with pulmonary diseases.

Endothelin (ET) is a broncho- and vasoconstrictive cytokine, but it also possesses proinflammatory and mitogenic activity. It is suggested to be involved in the pathogenesis of fibrotic lung diseases. We analyzed the concentration of ET 1 in the bronchoalveolar lavage (BAL) fluid in 95 patients with different lung diseases, among them 41 patients with interstitial lung diseases (13 fibrosing alveolitis in systemic sclerosis (FASS), 9 idiopathic pulmonary fibrosis (IFP), 8 sarcoidosis (S), 6 occupational lung disease (OLD), 5 other alveolitidies A), 27 patients with pneumonia, and 8 patients with chronic obstructive pulmonary disease (COPD). A heterogeneous group of 19 patients served as controls. The median ET concentration was 3.3 pg/ml. Significantly higher concentration was found in patients with FASS (5.8 pg/ml), IPF (5.0 pg/ml), and S (5.1 pg/ml) compared with OLD (2.8 pg/ml), A (1.9 pg/ml), COPD (1.5 pg/ml), and the control group (2.5 pg/ml). In pneumonia, the elevated ET concentration (4.1 pg/ml) was accompanied by a high alveolocapillary leakage. When normalized to BAL albumin concentration, only FASS presented with significantly elevated ET/albumin in the BAL compared with the control group (134.5 vs. 56.l pg/mg, p < 0.05). There were no correlations between ET and BAL differential cell count or pulmonary function tests. In current smokers, ET in BALF was significantly higher compared with non- or ex-smokers (3.9 vs. 2.0 pg/ml, p < 0.01), but not so the ET/albumin ratio (65.0 vs. 62.5 pg/mg). In summary, ET in the BAL is differentially expressed in distinct inflammatory and interstitial lung disease. Consistently high concentrations are found in FASS and elevated ET concentration could be discussed in IPF, sarcoidosis, and pneumonia. ET concentration in BAL is influenced by current smoking habits.

Adult↗
PubMed2002

Influence of acid-citrate-dextrose anticoagulant on blood quality in retransfusion systems after total knee arthroplasty.

The influence of acid-citrate-dextrose (ACD) anticoagulant on the blood quality was assessed in this prospective, randomized, controlled study. The clinical consequences with regard to retransfusion of drainage blood following total knee arthroplasty were evaluated. After total knee arthroplasty, retransfusion was performed utilizing a "SureTrans" retransfusion system in 81 patients. In 42 of them, blood was collected adding an ACD anticoagulant (group A), while in the remaining 39 patients blood was collected without any additives (group B). Blood losses were retransfused over a 6-h period after attaching the retransfusion system to the patient of either group. Blood samples of the 6-h blood collection were taken and analysed for several blood quality parameters. Significant differences were found in the platelet count (61,200+/-16,700 microl(-1) in group A versus 70,100+/-21,600 microl(-1) in group B, p=0.042), the lactate concentration (4.09+/-0.86 mmol/l vs 4.82+/-0.83 mmol/l, p<0.001), the pH (6.96+/-0.10 vs 7.18+/-0.06, p<0.001), as well as the protein content (5.44+/-0.57 g/dl vs 5.85+/-0.43 g/dl, p<0.001). These observed significant differences were, however, of no clinical relevance to the patients' treatment. Hemoglobin concentration, hematocrit, mean corpuscular volume (MCV), erythrocyte count, leukocyte count, concentration of free hemoglobin in the blood plasma (fHb), potassium concentration, lactate dehydrogenase (LDH), serotonin concentration, triglyceride concentration, free fatty acid concentration, and interleukin-6 concentration did not differ significantly. This study indicates that the blood quality in retransfusion systems is not substantially influenced by adding ACD anticoagulant.

Aged↗
PubMed2002

[Acupuncture in diseases of the locomotor system. Status of research and clinical applications].

Acupuncture has been used for over 2000 years for a wide variety of complaints with minimal side effects. Based on the experience in Chinese medicine and the anticipated positive effects, acupuncture has been widely accepted in Western medicine as well. Some clinical evidence supports the efficacy of acupuncture treatment, but randomized controlled trials have been conducted for only a few of all possible locomotive disorder indications, and the results have been equivocal. Other indications have not yet been systematically studied, and application is based on clinical experience and consensus among practitioners. One of the outcomes on which consensus appears to exist is that 10-20 sessions are generally necessary, and that initial improvement can be expected to occur by the 10th treatment. Rigorous trials should be conducted to improve clinical validity and provide scientific proof of the efficacy of acupuncture. Clinical trials like the German Acupuncture Trials (gerac), funded by the German health insurance companies, have been launched with the aim of furthering knowledge in this area.

Acupuncture Therapy↗
PubMed2002

[Acupuncture in the treatment of locomotive disorders - status of research and situation regarding clinical application].

Acupuncture has been used for over 2000 years for a wide variety of complaints with minimal side effects. Based on the experience in Chinese medicine and the anticipated positive effects, acupuncture has been widely accepted in Western medicine as well. Some clinical evidence supports the efficacy of acupuncture treatment, but randomized controlled trials have been conducted for only a few of all possible locomotive disorder indications, and the results have been equivocal. Other indications have not yet been systematically studied, and application is based on clinical experience and consensus among practitioners. One of the outcomes on which consensus appears to exist is that 10-20 sessions are generally necessary, and that initial improvement can be expected to occur by the 10th treatment. Rigorous trials should be conducted to improve clinical validity and provide scientific proof of the efficacy of acupuncture. Clinical trials like the German Acupuncture Trials (gerac), funded by the German health insurance companies, have been launched with the aim of furthering knowledge in this area.

Acupuncture Therapy↗
PubMed2002

Preweaning enrichment has no lasting effects on adult hippocampal neurogenesis in four-month-old mice.

Since both living in an enriched environment and physical activity stimulate hippocampal neurogenesis in adult mice, we endeavored to examine whether pre-weaning enrichment, a sensory enrichment paradigm with very limited physical activity, had similar effects on neurogenesis later in life. Mice were removed from the dams for periods of increasing length from post-natal day 7 to 21, and exposed to a variety of sensory stimuli. At the age of 4 months, significant differences could be found between previously enriched and nonenriched animals when spontaneous activity was monitored. Enriched mice moved longer distances, and spent more time in a defined center zone of the open field. Adult neurogenesis was examined by labeling proliferating cells in the dentate gyrus with bromodeoxyuridine (BrdU). Cell proliferation, survival of the newborn cells, and net neurogenesis were similar in both groups. Volumetric measurements and stereological assessment of total granule cell counts revealed no difference in size of the dentate gyrus between both groups. Thus, in contrast to postweaning enrichment, preweaning enrichment had no lasting measurable effect on adult neurogenesis. One of the parameters responsible for this effect might be the lack of physical activity in preweaning enrichment. As physical activity is an integral part of postweaning enrichment, it might be a necessary factor to elicit a neurogenic response to environmental stimuli. The result could also imply that baseline adult hippocampal neurogenesis is independent of the changes induced by preweaning enrichment and might not contribute to the sustained types of plasticity seen in enriched animals.

Animals↗
PubMed2002

BALF N-acetylglucosaminidase and beta-galactosidase activities in idiopathic pulmonary fibrosis.

The lysosomal enzymes N-acetylglucosaminidase (N-ACGA) and beta-galactosidase (beta-gal) are involved in cellular collagen metabolism and may, therefore, be markers of fibrosis in idiopathic interstitial pneumonias, such as idiopathic pulmonary fibrosis (IPF). N-ACGA and beta-gal were analyzed in the bronchoalveolar lavage fluid (BALF) of patients with the histologic pattern of usual interstitial pneumonia (UIP, n=10) and controls (n=9). Cellular distribution in BALF as well as the concentration of TGF-beta a well-known mediator of fibroblast matrix deposition were correlated to the enzyme activities in both groups of patients. We found that both, N-ACGA (UIP: 25.2 nmol/l s +/- 3.4; controls: 73 nmol/l s +/- 1.3) and beta-gal (UIP: 4.7 nmol/l s +/- 0.5; controls: 2.4 nmol/l s +/- 0.3) were elevated significantly in BALF of patients with IPF compared to that of control patients (P<0.003). This increase was paralleled by an increase in neutrophils (IPF: 17.9% +/- 21.8; controls: 5.4% +/- 6.3; P=0.03) and eosinophils (IPF: 2.0% +/- 1.5; controls: 0.2% +/- 0.45; P=0.002) in BALF fluid. In addition, N-ACGA activity correlated closely with lung function (FVC, TLC, and DLCO), transforming growth factor-beta (TGF-beta) in BALF (r=0.77, P=0.008) and activated lymphocytes (r=0.66, P=0.0021). Our findings suggest that measurement of lysosomal enzymes such as N-ACGA may represent a useful indicator of fibrotic activity in IPF.

Acetylglucosaminidase↗