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Biomedical subjects

M Orth

Publications and source records attributed to M Orth.

At least 19 recordsLinked to original sources
PubMed2007

[Pulmonary diseases and heart function].

The most severe cardiac sequel to lung disease is the load on the right ventricle due to pulmonary hypertension with the development of a cor pulmonale. This is characterized by hypertrophy and/or dilatation of the right ventricle because of a primary impairment of lung function and/or lung structure. The most important pathomechanisms for the development of pulmonary hypertension are vessel obliteration, mechanical lesions, primary vascular or extra-vascular inflammation and hypoxic vasoconstriction. Chronic obstructive pulmonary disease (COPD) is one of the most important reasons for chronic cor pulmonale. A further very common reason is obstructive sleep apnea syndrome, especially if combined with a COPD. In this case, the prevalence of cor pulmonale can reach 80%. The development of a chronic cor pulmonale is the most striking negative prognostic factor for these patients. Only 30% of COPD patients with cor pulmonale survive longer than 5 years, and only early detection of the disturbances to respiration which might potentially lead to cor pulmonale and their subsequent therapy are able to improve the patient's prognosis. Furthermore, pulmonary diseases may also have an impact on the left heart side in terms of an impairment of left heart function or by inducing severe arrhythmias . Thus, lung diseases may have both a significant impact on right and left heart performance.

Arrhythmias, Cardiac↗
PubMed2006

Cortical excitability predicts seizures in acutely drug-reduced temporal lobe epilepsy patients.

OBJECTIVE: To test the hypothesis that cortical excitability changes prior to seizures, using transcranial magnetic brain stimulation (TMS). METHODS: We studied 18 patients with unilateral temporal lobe epilepsy (TLE) twice using TMS: prior to (day 1) and following (day 3) reduction of antiepileptic drugs in a monitored inpatient setting. Short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF) were measured. Time since most recent seizure prior to day 1, and time until next seizure after day 3, were recorded. RESULTS: On day 1, prior to antiepileptic drug withdrawal, there were no correlations with recent or next seizures. On day 3, patients who had seizures in the subsequent 48 hours had weaker SICI and ICF in the hemisphere ipsilateral to seizure onset, vs patients who did not have seizures in the next 48 hours (p = 0.033). Additionally on day 3, there was a strong correlation between the difference between ICF and SICI in the ipsilateral hemisphere and time to next seizure (p < 0.001). CONCLUSIONS: Change in cortical excitability, measured with transcranial magnetic brain stimulation, may reflect a long-lasting and widespread pre-ictal state.

Acute Disease↗
PubMed2006

Beck Depression Inventory is a useful screening tool for major depressive disorder in Gilles de la Tourette syndrome.

This study determined the prevalence of and factors associated with comorbid major depressive disorder (MDD) in patients with Gilles de la Tourette syndrome (GTS). How a simple self-report instrument, the Beck Depression Inventory (BDI), correlates with clinical assessment of comorbid MDD in this population was assessed. In a continuous sample of 114 adult patients with GTS, assessed clinically using the Diagnostic and Statistical Manual of Mental Disorders-IV criteria, 26 (23%) patients met criteria for MDD; more severe tics as measured with the Yale Global Tic Severity Scale, conduct disorder in childhood or higher age at the time of assessment were associated with MDD. The BDI score had a high negative predictive value for diagnosis of MDD, but a low positive predictive value. Using the BDI as a screening tool for comorbid MDD in patients with GTS is suggested.

Adult↗
PubMed2006

[Long-term compliance of cpap-therapy--update, predictors and interventions].

CPAP (continuous positive airway pressure) is the therapy of choice for obstructive sleep apnea syndrome (OSAS). About 70 % of patients on CPAP use their device for at least 70 % of nights with an application-time of at least 4 hours per night. Severity of breathing disorder respectively disturbance of sleep architecture, degree of daytime sleepiness and patients' satisfaction with diagnostic and therapeutic procedures are good predictors of long-term CPAP-compliance. CPAP-compliance can be increased by intensive patient education. Alternative devices like for example Bilevel or auto-CPAP respectively cannot augment CPAP compliance.

Continuous Positive Airway Pressure↗
PubMed2006

[Cognitive deficits in patients with chronic obstructive pulmonary disease (COPD)].

INTRODUCTION: Patients with COPD present with impairments of their cognitive performance. The present study compares intelligence and memory performance as well as different aspects of attention in COPD patients and healthy controls. Additionally, potential factors influencing daytime performance are analyzed. PATIENTS AND METHODS: Neuropsychological testing was performed in 32 patients with COPD and 10 normal controls. The following aspects were evaluated: memory, intelligence, simple, selective and divided attention, sustained attention under stress and under monotonous conditions. RESULTS: There were no differences between COPD patients and normals with regard to divided attention, vigilance and memory. Patients with COPD demonstrated significantly worse results in terms of intelligence (p < 0.01) as well as simple (p < 0.01), selective (p < 0.05) and sustained attention (p < 0.01). No correlation existed between the severity of the disease (lung function, blood gas analysis, nocturnal oxygen saturation) and neuropsychological findings. Merely a relationship between memory function and slow-wave sleep or REM sleep was demonstrated. CONCLUSION: Impairments of cognitive performance in patients with COPD cannot be predicted on the basis of the severity of the disease. Therefore neuropsychological testing is recommended, especially when impairment of daytime function has to be quantified.

Adult↗
PubMed2006

Friedrich Nietzsche's mental illness--general paralysis of the insane vs. frontotemporal dementia.

OBJECTIVE: For a long time it was thought that Nietzsche suffered from general paralysis of the insane (GPI). However, this diagnosis has been questioned recently, and alternative diagnoses have been proposed. METHOD: We have charted Friedrich Nietzsche's final fatal illness, and viewed the differential diagnosis in the light of recent neurological understandings of dementia syndromes. RESULTS: It is unclear that Nietzsche ever had syphilis. He lacked progressive motor and other neurological features of a progressive syphilitic central nervous system (CNS) infection and lived at least 12 years following the onset of his CNS signs, which would be extremely rare for patients with untreated GPI. Finally, his flourish of productivity in 1888 would be quite uncharacteristic of GPI, but in keeping with reports of burgeoning creativity at some point in the progression of frontotemporal dementia (FTD). CONCLUSION: We suggest that Nietzsche did not have GPI, but died from a chronic dementia, namely FTD.

Dementia↗
PubMed2005

[Driving simulator performance in patients with obstructive sleep apnea syndrome: what consequences for driving capability?].

BACKGROUND AND OBJECTIVE: Patients with obstructive sleep apnea (OSA) have an increased accident risk. The German Society of Sleep Research and Sleep Medicine (DGSM) recommends for patients with OSA and daytime sleepiness that their driving ability should be re-established 6 weeks after the initiation of CPAP (continuous positive airway pressure), with documentation of therapeutic effects on daytime symptoms and performance. The present study was conducted to investigate whether an improvement of driving ability can be documented in neuropsychological tests and a simulated driving situation 14 days after the initiation of CPAP. PATIENTS AND METHODS: Driving simulation and neuropsychological tests of vigilance were conducted in 36 patients (36 males, aged 54 9 years) with OSAS before and 2 (n=23), 14 (n=18) and 42 days (n=17) after initiation of CPAP. RESULTS: Vigilance tests showed only slight changes under CPAP. Frequency of accidents during driving simulation was reduced after 14 days of CPAP, but a statistically remarkable decrease was achieved only on day 42. In contrast, concentration faults were reduced after 2 and 14 days of CPAP. CONCLUSIONS: In OSA-patients improvement of daytime performance in a simulated driving situation can be documented 14 days after initiation of CPAP. There is need for investigating larger cohorts of patients so that current recommendations for driving licensing can be modified and permission to drive can be given earlier.

Automobile Driving↗
PubMed2005

Halothane and propofol differentially affect electroencephalographic responses to noxious stimulation.

BACKGROUND: Anaesthetics blunt neuronal responses to noxious stimulation, including effects on electroencephalographic (EEG) responses. It is unclear how anaesthetics differ in their ability to modulate noxious stimulation-evoked EEG activation. We investigated the actions of propofol and halothane on EEG responses to noxious stimuli, including repetitive electrical C-fibre stimulation, which normally evokes neuronal wind-up. METHODS: Rats were anaesthetized with halothane (n=8) or propofol (n=8), at 0.8x or 1.2x the amount required to produce immobility in response to tail clamping [minimum alveolar concentration (MAC) for halothane and median effective dose (ED(50)) for propofol]. We recorded EEG responses to repetitive electrical stimulus trains (delivered to the tail at 0.1, 1 and 3 Hz) as well as supramaximal noxious tail stimulation (clamp; 50 Hz electrical stimulus, each for 30 s). RESULTS: Under halothane anaesthesia, noxious stimuli evoked an EEG activation response manifested by increased spectral edge frequency (SEF) and median edge frequency (MEF). At 0.8 MAC halothane, the tail clamp increased the MEF from approximately 6 to approximately 8.5 Hz, and the SEF from approximately 25.5 to approximately 27 Hz. At both 0.8 and 1.2 MAC halothane, similar patterns of EEG activation were observed with the 1 Hz, 3 Hz and tetanic stimulus trains, but not with 0.1 Hz stimulation, which does not evoke wind-up. Under propofol anaesthesia, noxious stimuli were generally ineffective in causing EEG activation. At 0.8 ED(50) propofol, only the tail clamp and 1 Hz stimuli increased MEF ( approximately 8 to approximately 10-10.5 Hz). At the higher propofol infusion rate (1.2 ED(50)) the repetitive electrical stimuli did not evoke an EEG response, but the tetanic stimulus and the tail clamp paradoxically decreased SEF (from approximately 23 to approximately 21.5 Hz). CONCLUSIONS: Propofol has a more significant blunting effect on EEG responses to noxious stimulation compared with halothane.

Anesthetics, Inhalation↗
PubMed2005

Soluble adhesion molecules in Gilles de la Tourette's syndrome.

To investigate the immune-mediated response in TS, and its relationship with streptococcal infection, we measured serum levels of soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in patients with TS, compared to healthy and diseased controls. Soluble VCAM-1 and sE-selectin were significantly elevated in children and adults with TS, and sVCAM-1 was higher among anti-basal ganglia antibodies (ABGA)-positive adults with TS. No correlation of adhesion molecule levels to clinical severity or anti-streptococcal antibodies was observed. Children with Sydenham's chorea and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) showed an increased level of sICAM-1, but not sVCAM-1 and sE-selectin. These results provide initial evidence for a role of adhesion molecules and systemic inflammation in TS, and support the hypothesis of an ongoing immune-mediated process in this condition.

Adolescent↗
PubMed2005

Excitability of motor cortex inhibitory circuits in Tourette syndrome before and after single dose nicotine.

The pathophysiology underlying the involuntary tics of Gilles de la Tourette syndrome (GTS) remains unknown. Here we used transcranial magnetic stimulation (TMS) to examine the excitability of two different inhibitory systems in the human motor cortex: short interval intracortical inhibition (SICI) and short interval afferent inhibition (SAI) in 10 healthy non-smoking controls and eight untreated non-smoking patients with GTS. Compared with the healthy control group, both SICI (measured at a range of conditioning intensities) and SAI were reduced in patients. This is consistent with the suggestion that reduced excitability of cortical inhibition is one factor that contributes to the difficulty that patients have in suppressing involuntary tics. In addition, the reduced SAI indicates that impaired intracortical inhibition may not be limited to the motor cortex but also involves circuits linking sensory input and motor output. A single dose of nicotine reduced tic severity as assessed by blind video scoring in the majority of patients. In addition, it abolished the difference between patients and controls in SICI and SAI. There was no effect of nicotine, and no difference between controls and patients in measures of motor or SICI threshold. This indicates that cholinergic input can modulate the efficiency of SICI and SAI differently in GTS and healthy controls.

Adult↗
PubMed2005

Caffeine has no effect on measures of cortical excitability.

OBJECTIVE: To assess the effect of caffeine on motor thresholds, short interval intra-cortical inhibition (SICI), intra-cortical facilitation (ICF) and cortical silent periods in a placebo controlled double-blinded trial. METHODS: In eleven healthy non-smoking subjects the following parameters were measured using transcranial magnetic stimulation (TMS): motor thresholds (rest, RMT and active, AMT), SICI and ICF at different conditioning stimulus intensities (60, 70, 80, 90% AMT), cortical silent periods at 130, 150 and 175% AMT, and size of motor evoked potential at rest at 110, 125 and 150% RMT. Measurements were repeated after one cup of decaffeinated coffee. On another day, measurements were obtained before and after one cup of decaffeinated coffee that contained caffeine (3 mg/kg bodyweight). Caffeine concentrations were measured in serum before and after experiments. Experiments were conducted and data were evaluated blinded to the experimental condition. RESULTS: The results of repeated measurements of all parameters were similar comparing experiments on each day, or when comparing the caffeine arm of the study with the placebo arm. CONCLUSIONS: Caffeine in a concentration similar to that in a strong cup of coffee does not have a major effect on TMS measures of motor cortex excitability. SIGNIFICANCE: In healthy controls, the design of TMS experiments that investigate the parameters assessed in this TMS study does not need to control for caffeine.

Adult↗
PubMed2005

Activity of sirolimus in patients with myelodysplastic syndrome--results of a pilot study.

The pathophysiology of the myelodysplastic syndromes (MDS) involves disturbed regulation of angiogenesis, apoptosis, proliferation and differentiation as well as immune surveillance. Increasing data suggest that sirolimus might affect these pathways positively, thus being of possible therapeutic benefit in patients with this disease. Nineteen patients (n = 19) with a median age of 72 years (range 54-80 years) diagnosed with MDS received sirolimus orally with a target blood concentration of 3-12 ng/ml. Sirolimus was administered for a median of 3.7 months (range 0.3-11 months). Three patients [1 x refractory anaemia with excess blasts (RAEB)-2, 1 x RAEB-1, 1 x refractory cytopenia with multilineage dysplasia] showed either a major (1 x platelet, 1 x neutrophil) or a minor (1 x erythroid, 2 x platelet) haematological response according to International Working Group criteria. Major side-effects were hyperlipidaemia (n = 4), stomatitis (n = 3), thrombocytopenia (n = 2) and urinary tract infection (n = 1). These data suggest that sirolimus has activity in a subset of patients with more advanced MDS.

Administration, Oral↗
PubMed2005

Characterization of matrix metalloproteinases in denervated muscle.

In a nerve crush model of denervation, we examined muscle matrix metalloproteinase (MMP) expression, localization and activity. In normal muscle, MMP mRNA levels were low, and immunohistochemically MMPs were distributed around the muscle fibre with MMPs-3, -7 and -9 also staining at the neuromuscular junction. Seven days after nerve crush, muscle MMP immunoreactivity, especially MMP-12 and MMP-14, became irregularly distributed. At 20 days reinnervation of the muscle was observed, and some restitution of the normal pattern of immunoreactivity was noted concomitant with a higher level of MMP mRNA expression. In situ zymography showed that MMP activity was very weak in normal muscle whereas it was increased up to 40 days following denervation. Our results suggest that MMPs in muscle are involved in the tissue changes following denervation. Further experiments are required to test the hypothesis that MMP inhibition may be beneficial in protecting muscle from excessive remodelling following denervation and therefore improve reinnervation.

Animals↗
PubMed2005

ALS-IgG-induced selective motor neurone apoptosis in rat mixed primary spinal cord cultures.

There is evidence that in sporadic amyotrophic lateral sclerosis (ALS) immunological mechanisms may be involved in the pathophysiology of the disease. We tested whether purified IgG from ALS patients induce cell death in rat mixed primary spinal cord cultures and compared this with the effect of IgG purified from patients with Guillain-Barré syndrome (GBS) or from healthy donors. Treatment with ALS-IgG increases caspase-3 apoptosis when compared with control IgG or with GBS-IgG, but does not induce death by necrosis. Because ALS is characterized by the selective loss of motor neurones, we next assessed the differential effect of ALS-IgG on motor neurones or astrocytes. We showed, semiquantitatively, that motor neurones are more susceptible to apoptosis when cultures were treated with ALS-IgG compared with control-IgG. In conclusion, we have demonstrated in primary spinal cord cultures that IgG from patients with ALS induces apoptosis selectively in motor neurones, and that the caspase-3 pathway is involved. This suggests that immunological mechanisms may contribute to the selective loss of motor neurones in ALS.

Adolescent↗
PubMed2005

Mirtazapine increases cortical excitability in healthy controls and epilepsy patients with major depression.

BACKGROUND: Epilepsy is often complicated by depression requiring antidepressant treatment. Such treatment might be proconvulsive. OBJECTIVE: To examine the effects of the noradrenergic and specific serotonergic antidepressant mirtazapine on motor cortex excitability in epilepsy patients with depression and in healthy controls, using transcranial magnetic stimulation (TMS). METHODS: Seven clinically depressed epilepsy patients treated with anticonvulsant drugs and six healthy volunteers were studied. Before intake of mirtazapine and 24 hours afterwards (and also three weeks afterwards in the patients), the active and resting motor threshold (AMT, RMT), the size of the motor evoked potential (MEP), the cortical silent period (SP), and intracortical inhibition/facilitation and intracortical facilitatory I wave interactions were determined using single and paired pulse TMS. RESULTS: At baseline, AMT and RMT were higher (p = 0.049 and p = 0.04, respectively) and the ratio SP duration/MEP area greater in patients (p = 0.041). In patients but not in healthy subjects AMT was lower 24 hours after intake of mirtazapine (p = 0.028). Mirtazapine had no significant effect on the MEP size, duration of the SP, or the ratio of SP duration to MEP size in patients. The duration of the SP was longer (p = 0.037) but the ratio of SP duration to MEP size remained similar in healthy subjects after mirtazapine. There were no significant differences in paired pulse measures between the two groups either at baseline or after mirtazapine. CONCLUSIONS: Mirtazapine increased neuronal excitability of pyramidal tract axons in an activated state in both healthy controls and epilepsy patients with major depression.

Adult↗
PubMed2005

Driving simulator and neuropsychological [corrected] testing in OSAS before and under CPAP therapy.

Patients with obstructive sleep apnoea syndrome (OSAS) have an increased car accident rate. Investigations on accident frequency are based on case history, insurance reports and driving simulator studies. The present study combines neuropsychological testing of different attention aspects engaged in driving a car and driving simulation to evaluate a suitable instrument for assessing therapeutic effects of continuous positive airway pressure (CPAP). Driving simulator investigation and neuropsychological testing of alertness, vigilance and divided attention were performed in 31 patients with polysomnographically confirmed OSAS (apnoea-hypopnoea index 24.8+/-21.5.h(-1)) before, and 2 and 42 days after initiation of CPAP. Divided attention and alertness improved significantly during CPAP, whereas vigilance remained unchanged. However, accident frequency (OSAS before therapy: 2.7+/-2.0; 2 days after CPAP: 1.5+/-1.4; 42 days after CPAP: 0.9+/-1.3) and frequency of concentration faults (OSAS before therapy: 12.4+/-5.1; 2 days after CPAP: 6.5+/-3.9; 42 days after CPAP: 4.9+/-3.3) decreased in the simulated driving situation after 2 and 42 days of therapy. There was no relation between accident frequency, concentration faults and daytime sleepiness, as measured by the Epworth Sleepiness Scale, and polysomnographic or neuropsychological findings, respectively. In conclusion, the present results suggest that driving simulation is a possible benchmark parameter of driving performance in obstructive sleep apnoea syndrome patients.

Accidents, Traffic↗
PubMed2004

Subthreshold rTMS over pre-motor cortex has no effect on tics in patients with Gilles de la Tourette syndrome.

OBJECTIVE: A previous study showed no effect of 1Hz repetitive transcranial magnetic stimulation (rTMS) on tics in Gilles de la Tourette Syndrome (GTS). We modified the rTMS protocol in order to investigate some of the possible methodological reasons for the negative outcome in that study. METHODS: In a single blinded placebo-controlled cross-over study in five GTS patients without obsessive compulsive disorder we probed whether longer trains (1800 stimuli) of 1 Hz pre-motor cortex rTMS at 80% of active motor threshold and application to both hemispheres can improve tics in GTS. This was measured with the Yale Global Tic severity rating scale, the MOVES self-rating scale and video analysis. RESULTS: We found no significant effect of either left pre-motor cortex stimulation alone, or left pre-motor followed by right pre-motor cortex stimulation. CONCLUSIONS: These results suggest that the rTMS protocol used in this study is not useful for the treatment of tics in GTS. SIGNIFICANCE: rTMS protocols need to be modified substantially in order to explore their potential for the treatment of tics in GTS.

Adult↗