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Biomedical subjects

P Schüler

Publications and source records attributed to P Schüler.

At least 19 recordsLinked to original sources

Efficacy and safety of high-dose cabergoline in Parkinson's disease.

OBJECTIVES: To assess the efficacy and safety of high-dose (up to 20 mg/day) cabergoline in Parkinson's disease (PD) patients with motor fluctuations and/or dyskinesias. MATERIALS AND METHODS: Thirty-four PD patients had cabergoline up-titrated and their levodopa (L-dopa) reduced over a maximum of 20 weeks, followed by at least 6 weeks steady cabergoline dosing. Primary endpoint was change in mean hyperkinesia intensity at the final visit (week 26). RESULTS: Mean (+/- SD) cabergoline was increased from 6.43 +/- 2.66 to 12.78 +/- 5.67 mg/day and mean L-dopa reduced from 606.6 +/- 263.9 to 370.6 +/- 192.5 mg/day. A significant reduction (P < 0.001) in mean hyperkinesia intensity occurred from baseline (day 0) to week 26. Improvements in 'on with dyskinesias', mean dystonia intensity (P < 0.05), time spent in 'severe off' condition, severity of 'off' periods as well as clinical/patient global impression, and health-related quality of life were observed. Twenty-four drug-related adverse events were recorded of which four were regarded as serious. CONCLUSION: High-dose cabergoline was well tolerated and provided significant improvements in the Parkinson symptomatology and a reduced requirement for L-dopa.

Adolescent↗

Microcirculation and excretory function of the liver under conditions of carbon dioxide pneumoperitoneum.

BACKGROUND: To date, the effects of increased abdominal pressure, as given during carbon dioxide (CO(2)) pneumoperitoneum, on hepatic microcirculation and biliary excretion are unknown. METHODS: Using a custom-made peritoneal cavity chamber, we performed intravital microscopy of the left liver lobe under conditions of CO(2) pneumoperitoneum in a rat model. In addition, biliary excretion was assessed. RESULTS: The establishment of a CO(2) pneumoperitoneum of 4 or 8 mmHg resulted in sinusoidal perfusion failure that was more pronounced in the periportal regions than in the midzonal and pericentral regions of the liver acinus. Biliary excretion was considerably reduced at an intraabdominal pressure of 8 mmHg. Leukocyte-endothelial cell interactions increased significantly in both hepatic sinusoids and postsinusoidal venules. CONCLUSION: Alterations in hepatic microcirculation and liver function must be taken into consideration in any kind of laparoscopic surgery and may be of particular clinical relevance in patients with liver pathology.

Animals↗

Ampicillin + sulbactam vs clindamycin +/- cephalosporin for the treatment of aspiration pneumonia and primary lung abscess.

Aspiration pneumonia, necrotising pneumonia and primary lung abscess are complications arising from the aspiration of infectious material from the oral cavity or stomach. There is limited information on optimal antibacterial therapeutic regimens. Patients with pulmonary infection following aspiration (n = 95) were included in a prospective, open, randomised, comparative multicentre trial to compare the safety, clinical and bacteriological efficacy of ampicillin + sulbactam vs. clindamycin +/- cephalosporin. Treated patients (n = 70) received sequential antibiotic therapy with either ampicillin + sulbactam (n = 37) or clindamycin (n = 33), with or without a second- or third-generation cephalosporin, administered until the complete resolution of clinical and radiological abnormalities. Definite or presumptive pathogens were isolated from 58 patients. Mean duration of therapy was 22.7 days for ampicillin + sulbactam and 24.1 days for clindamycin. In patients treated with ampicillin + sulbactam, the clinical response was 73.0% at the end of therapy and 67.5% 7-14 days after therapy. For clindamycin, the rates were 66.7% and 63.5%, respectively. Bacteriological response was similar in both treatment arms. Nine patients died (12.9%), with a Simplified Acute Physiology Score of > 30 points being the only significant predictive factor for therapeutic failure. Ampicillin + sulbactam and clindamycin +/- cephalosporin were both well-tolerated and proved equally effective in the treatment of aspiration pneumonia and lung abscess.

Adolescent↗

Effect of laparotomy and CO(2) pneumoperitoneum on tumor growth of human colon carcinoma and expression pattern of tumor-associated proteins in the SCID mouse.

BACKGROUND AND AIMS: The impact of laparoscopy on tumor progression is still unclear. This study investigated the effect of CO(2) pneumoperitoneum on the intra-abdominal growth of human colon carcinoma independently of the effect of the immune system. METHODS: SCID mice underwent either median laparotomy or laparoscopy. Human colon carcinoma cells were implanted into the upper abdomen. The control group was not operated on following cell injection. Tumor growth and the protein expression pattern of proliferation marker Ki67, cell-cell adhesion molecules E-cadherin, alpha- and beta-catenin, and cell-extracellular matrix adhesion molecules CD44 v5 and v6 in tumor tissue were analyzed on postoperative day 14. RESULTS: Total tumor volume in the laparoscopy group significantly exceeded that in the laparotomy group. Immunohistochemistry revealed reduced expression of alpha-catenin and elevated expression on beta-catenin and CD44 v5 in the tumor tissue of the laparoscopy group. CONCLUSION: The expression pattern of proteins associated with tumor progression and the increase in tumor growth suggest an increased risk of laparoscopy at least for the growth of advanced human colon carcinoma.

Animals↗

A peritoneal cavity chamber for intravital microscopy of the liver under conditions of pneumoperitoneum.

BACKGROUND: Intravital microscopy allows direct visualization of the hepatic microvasculature. We report on a novel application of this technique using a chamber model that simulates the conditions of pneumoperitoneum. METHODS: For this purpose, we designed a peritoneal cavity chamber for rats. In the present study, we evaluated the technical procedure without any induction of increased intraabdominal pressure to assess undisturbed hepatic microcirculation. Intravital microscopy of the liver was performed in 12 rats. Animals that underwent the same operative procedure without the chamber served as controls (n = 12). RESULTS: Hepatic sinusoidal perfusion rate, leukocyte-endothelial cell interaction, and bile flow showed no significant differences between the groups. Operating time was longer in the chamber group. CONCLUSION: The peritoneal cavity chamber is an attractive approach for the study of hepatic microvascular, cellular, and molecular mechanisms that are important to our understanding of the potential harmful effects of laparoscopy on hepatic circulation and liver function.

Animals↗

Prognostic factors influencing surgical management and outcome of gastrointestinal stromal tumours.

BACKGROUND: The purpose of this study was to review surgical experience with gastrointestinal stromal tumours (GISTs) at a single tertiary university hospital, and to identify morphological and genetic prognostic markers of tumour progression. METHODS: Forty-eight GISTs from 39 patients were reviewed retrospectively. The prognostic significance of DNA copy number changes, measured by comparative genomic hybridization (CGH), and morphological markers in low-risk and high-risk tumours were investigated. RESULTS: Significantly more patients died from disease after incomplete tumour resection than after complete primary resection (P = 0.020). Tumour size of 5 cm or greater, mitotic count of 2 or more, and proliferative activity greater than 10 per cent were significantly associated with a shorter recurrence-free survival (P = 0.020, P = 0.001 and P = 0.002 respectively). Patients with low-risk tumours had a significantly better outcome than those with high-risk GISTs, both in terms of overall and recurrence-free survival (P < or = 0.001). CGH performed on 16 tumours revealed fewer DNA sequence copy number changes in low-risk than in high-risk GISTs. Non-progressive GISTs contained significantly fewer genetic alterations than recurrent or metastatic tumours (P < 0.001). Only tumours with more than five changes showed disease progression. CONCLUSION: Complete surgical resection is the most important means of cure for GISTs. DNA copy number changes are related to the behaviour of these tumours and may serve as additional prognostic markers.

Adult↗

[Analgesic effect of the selective noradrenaline reuptake inhibitor reboxetine].

BACKGROUND: Reboxetine is a selective noradrenaline reuptake inhibitor (NARI). As noradrenaline plays a relevant role in antinociceptive mechanisms, the hypothesis was investigated in this study whether reboxetine has analgetic efficacy. METHODS: Twenty-four healthy volunteers were investigated in a crossover design. Reboxetine (2 x 2 mg) or placebo were given for 5 days with the "crossover" following a one-day washout in between. The primary end-points were the N1 and P2 amplitudes of laser evoked somatosensory potentials (laser SEP) of vertex EEG. In addition, visual analogue scales (VAS, 100 mm) were used. RESULTS: Reboxetine showed a higher analgesic potency than placebo, with a statistically significant superiority in capsaicinirritated skin--in the objective tests (laser SEP, P < 0.0001 for N1 and P = 0.0002 for P2) as well as in the subjective pain measurements (VAS, P < 0.0003). Besides pain, the subjective feelings of burning and itching were lower with reboxetine than with the placebo. CONCLUSIONS: The hypothesis that a selective noradrenergic substance could be of analgesic efficacy was proven the first time experimentally. Reboxetine reduced the N1 and the P2 components of the laser SEP, which speaks for central and peripheral mechanisms of action.

Adolescent↗

Treatment of idiopathic restless legs syndrome (RLS) with the D2-agonist cabergoline--an open clinical trial.

STUDY OBJECTIVES: To define the effective dose of cabergoline and to evaluate the tolerability and efficacy of cabergoline in patients with restless legs syndrome (RLS). DESIGN: Treatment of idiopathic RLS patients with cabergoline in a 12-week open label trial. Patients on levodopa therapy were allowed to either stop levodopa prior to study entry or to continue, taper or discontinue levodopa during the study. Efficacy parameters were assessed by polysomnography and subjective ratings at baseline and at week 12. Primary efficacy parameters were the number of PLM and total sleep time. SETTING: Dept. of Neurology, Sleep Disorders Center PATIENTS: Nine patients with moderate to severe RLS (age 38.1 to 64.3 years, mean 54.1 years) who had experienced insufficient benefit under levodopa therapy and/or in part developed daytime augmentation participated. At study entry five patients were still under levodopa therapy (400-800 mg). INTERVENTIONS: Up-titration of cabergoline (single evening dose) until RLS symptoms clearly improved. Initial comedication with domperidone 20 mg t.i.d. MEASUREMENTS AND RESULTS: At the endpoint all patients were on cabergoline monotherapy (mean dosage 2.1 mg, range 1 to 4 mg). Domperidone was stopped in all patients due to good tolerability. Polysomnographic data showed a significant reduction of the number of periodic leg movements (PLM) (195.8+/-109.1 (baseline) vs. 26.4+/-40.2 (12 weeks cabergoline monotherapy; p=0.002), PLM arousals (51.7+/-42.3 vs. 6.4+/-11.2; p=0.017) and PLM awakenings (10.4+/-7.8 vs. 1.0+/-1.7; p=0.001). Total sleep time was prolonged (302.7+/-50.7 vs. 379.4+/-59.8 min; p=0.018), sleep latency shortened (42.4+/-49.1 vs. 16.3+/-22.8 min; p=0.214) and sleep efficiency increased (63.1+/-10.5 vs. 79.1+/-12.5%; p=0.017). All patients reported a impressive relief or became free of RLS symptoms. CONCLUSION: Cabergoline is effective and well tolerated in restless legs syndrome especially in patients with severe RLS and those who developed augmentation under levodopa therapy.

Adult↗

[Ictal syncopes. Cardiac sympathetic innervation disorder as the etiology?].

We report 3 cases of an ictal sinus arrest. All patients suffered from temporal lobe epilepsy (TLE). Seizures were monitored with simultaneous video-eeg during preoperative epilepsy diagnosis. One patient with cortical dysplasia, who frequently suffered from long lasting syncopes, had a nearly completely missing cardiac sympathetic innervation in MIBG-SPECT (=Meta-Iodide-Benzyle-Guanidine-single-photon-emission tomography). Cardiac investigation including long-term ECG and echocardiography had shown normal findings. After epilepsy surgery the syncopal events in all patients disappeared. A dominant parasympathetic ictal stimulus following excitation of the reticular formation might cause the ictal bradycardia and sinus arrest. A missing sympathetic innervation, possibly occurring as fehlbildung together with cortical dysplasia, which makes autoregulation impossible, might then be the explanation for sudden cardiac ictal death.

Adult↗

Penetration of sparfloxacin and ciprofloxacin into alveolar macrophages, epithelial lining fluid, and polymorphonuclear leucocytes.

Sparfloxacin (SPX), a novel fluoroquinolone with a broad spectrum of antibacterial activity, has been shown, in vitro, to be more effective against common pulmonary pathogens, particularly Streptococcus pneumoniae, Mycoplasma pneumoniae and some intracellular organisms, than ciprofloxacin (CPX). The objective of this open, comparative, randomized study in two parallel groups was to assess the serum concentrations and penetration of SPX and CPX into alveolar macrophages (AMs), epithelial lining fluid (ELF), and peripheral polymorphonuclear leucocytes (PMNs). Patients received either a single oral dose of SPX, 400 mg (16 patients), or CPX, 500 mg (15 patients), at various times before a routine diagnostic bronchoscopy was performed. Antibiotic concentrations were determined by using a microbiological assay. The median serum elimination half-lives were 17.3 h for SPX and 5.3 h for CPX. Peak levels (median+/-68% confidence range) of CPX were attained in AMs (7.6+/-1.7 mg x L(-1)) at 5 h after admission, and in both ELF (2.13+/-0.91 mg x L(-1)) and PMNs (9.1+/-6.2 mg x L(-1)) at 2.5 h after administration. SPX achieved comparable peak levels in PMNs (median+/-68% range, 9.4+/-1.1 mg x L(-1) at 5 h), but peak concentrations attained in AMs and ELF (35.1+/-15.4 and 32.2+/-28.2 mg x L(-1), respectively, at 24 h) were several times higher than those of CPX. SPX demonstrated substantially greater accumulation in all three sites than did CPX (peak site to serum ratios of 11.0+/-4.3, 65.5+/-28.4 and 63.0+/-66 versus 4.94+/-0.64, 10.6+/-3.7 and 10.6+/-3.7 for PMNs, AMs and ELF, respectively). The results indicate, that sparfloxacin has a long elimination half-life and that it achieves higher concentrations in alveolar macrophages and epithelial lining fluid than ciprofloxacin. Site concentrations of sparfloxacin greatly exceeded the minimal inhibitory concentrations of common respiratory pathogens.

Anti-Infective Agents↗

Probable Creutzfeldt-Jakob disease after a cadaveric dural graft.

A 26-year old female who had received a cervical cadaveric dural graft 7 years earlier developed psychotic behavior and generalized myoclonic jerks. Following rapid deterioration and appearance of high-charge sharp periodic waves on electroencephalography she died within two months. We believe that this patient is the first German who acquired Creutzfeldt-Jakob disease by dural implant.

Adult↗

Chemosensory event-related potentials in patients with temporal lobe epilepsy.

We investigated chemosensory functions in patients with temporal lobe epilepsy (TLE) to discover whether olfactory and trigeminal stimuli applied either ipsilaterally or contralaterally to the epileptic focus are processed differently. Twenty-two patients were investigated, 12 of whom had epilepsy with a focus located in left temporal lobe (LTL). The remaining 10 patients had a right temporal lobe (RTL) focus. Input from the trigeminal system was examined by use of CO2; input from the olfactory system was evaluated with vanillin and hydrogen sulfide as stimuli. Chemosensory function was assessed by evaluation of chemosensory event-related potentials (CSERP) and the patients' verbal reports in an odor identification test. In both groups of patients, prolonged CSERP latencies were noted after stimulation of the left nostril with CO2 as compared with stimulation of the right nostril. In contrast, a different pattern emerged for olfactory stimuli. After right-sided olfactory stimulation, latencies were prolonged in patients with right-sided epileptical foci. Similarly, when the left nostril was stimulated in patients with a left-sided focus, CSERP latencies were prolonged. Thus, neocortical processing of olfactory, but not trigeminally mediated information evidently is affected by functional lesions of the temporal lobe. After olfactory stimulation in patients with a right-sided focus, the distribution of amplitudes was different from normal. Moreover, analyses showed nonoverlapping 95% confidence intervals (CI) for latency N1 when vanillin was applied to the right nostril. These results indicate that RTL may play a different role in processing of olfactory information as compared with LTL.

Adult↗

Magnetic source localization and morphological changes in temporal lobe epilepsy: comparison of MEG/EEG, ECoG and volumetric MRI in presurgical evaluation of operated patients.

Is MEG source analysis able to precisely locate the primary focal epileptic activity? 22 patients with pharmacoresistant temporal lobe epilepsy were recorded during presurgical evaluation simultaneously with multichannel MEG/EEG and invasive (subdural) electrodes to evaluate the increase of information gained by MEG concerning the localization of focal epileptic activity and lesions. With this systematic study it should become clearer how often MEG can establish a diagnostic bridge between function and morphology. In addition, MEG localization accuracy of focal epileptic activity was to be validated empirically by invasive EEG recordings and postsurgical outcome. Spikes in the MEG were used for magnetic source localization, and the result was combined with magnetic resonance imaging (MRI). All patients definitely suffered from temporal lobe epilepsy and revealed a structural abnormality in MRI. 17 patients with lesions in the temporal lobe were operated meanwhile and became markedly improved or seizure free. In 7 of 8 patients with a tumor and validated operation outcome, a very close correlation of the 3D-magnetic source localization and the border of the tumor in the brain was found (distance less than 10 mm). In 8 of 9 patients with a temporal/hippocampal atrophy and validated operation outcome, dipoles of epileptiform activity were located within the atrophic lobe.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

[Anxiety attacks and epileptic seizures. Determining similarities based on a case report].

A patient suffering from panic attacks without any other clinical signs of epilepsy showed epileptic-form activity in sleep-deprivation EEG. After therapy with carbamazepine, the intensity and number of the panic attacks dropped significantly, whereas therapy with a tricyclic antidepressant had had no effect. Thus, even isolated panic attacks may have an epileptogenic background and should be taken into account in differential diagnosis.

Adult↗

Brain-stem lesions in the course of a presurgical re-evaluation by foramen-ovale electrodes in temporal lobe epilepsy.

Two of 4 patients who were re-evaluated by means of foramen-ovale electrodes in the course of presurgical monitoring suffered a brain-stem lesion. Only 1 of these 2 patients already had a temporal resection. None of 55 patients who underwent this procedure for the first time had such a complication. We conclude that this electrode technique is not indicated to evaluate patients a second time, even if no surgical resection has been performed between the 2 recording sessions.

Brain Diseases↗