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Biomedical subjects

M Orth

Publications and source records attributed to M Orth.

At least 37 records · Page 2Linked to original sources

[Acute severe asthma in older adults].

The underlying causes of acute severe or life threatening asthma are infections with respiratory viruses or Mycoplasma pneumoniae, rather than bacterial infections. In addition, exposure to various agents such as allergens, non-specific irritants or drugs, and inadequate long-term treatment may be responsible. High flow oxygen therapy, high dose topic beta(2)-agonists and systemic glucocorticosteroids should be used as baseline therapy in outpatients. In hospital, intravenous therapy-eventually including sedatives-can be administered under controlled or intensive care conditions. In patients with increasing respiratory pump weakness and alveolar hypoventilation, non-invasive and/or invasive mechanical ventilation may be required. In ventilated asthma patients permissive hypercarbia has been shown to reduce complications such as pneumothorax. Bronchoscopy and bronchial lavage are recommended for patients ventilated with increasing pressures or when atelectasis occurs.

Acute Disease↗

The cortical silent period: intrinsic variability and relation to the waveform of the transcranial magnetic stimulation pulse.

OBJECTIVE: To assess the variability of the duration of the contralateral cortical silent period (CSP) between individuals and to assess the effect of different transcranial magnetic stimulation (TMS) pulse waveforms. METHODS: In Expt. 1, CSP duration, and the motor-evoked potential (MEP) amplitude and area were measured in the first dorsal interosseous muscle (FDI) of 11 subjects on 3 separate occasions using a TMS intensity of 150% active motor threshold (AMT). In Expt. 2, the stimulation intensity was varied between 100% AMT and 150% AMT. In both sets of experiments, 3 types of TMS pulse were used: monophasic posterior-anterior (PA) induced current in the brain, monophasic anterior-posterior induced current (AP), and biphasic PA/AP stimulation. RESULTS: Experiment 1: Between-subject variation in CSP duration was high. In addition, the duration after PA stimulation was significantly shorter than after AP or PA/AP stimulation. However, there was a good correlation between CSP duration and the area, or amplitude, of the MEP. This meant that calculating the ratio of duration/amplitude or duration/area reduced intersubject variability and eliminated differences between TMS pulses. Experiment 2: increasing stimulation intensity increased the mean value of all parameters, but with significantly lower values for PA than other forms of stimulation. The ratios of duration/amplitude or duration/area did not differ between current flow directions and were relatively constant for intensities 130-150% AMT. CONCLUSIONS: Between-subject variation in the duration of the CSP is high. A given intensity of stimulation (expressed in %AMT) produces a shorter CSP for PA stimulation than for AP or PA/AP stimulation. SIGNIFICANCE: If the ratio (CSP duration)/(MEP size) is calculated, then intersubject variability is reduced, and TMS pulse type differences are eliminated.

Adult↗

G209A mutant alpha synuclein expression specifically enhances dopamine induced oxidative damage.

Alpha synuclein protein may play an important role in familial and sporadic Parkinson's disease pathology. We have induced G209A mutant or wild-type alpha-synuclein expression in stable HEK293 cell models to determine if this influences markers of oxidative stress and damage under normal conditions or in the presence of dopamine or paraquat. Induced wild-type or mutant alpha-synuclein expression alone had no effect upon levels of oxidative stress or damage, as measured by glutathione levels or aconitase activity. Both wild-type and mutant alpha-synuclein expression decreased the oxidative damage induced by paraquat, although the protection was less marked with mutant alpha-synuclein expression. This suggests that alpha-synuclein expression may either have anti-oxidant properties or may upregulate cellular antioxidant levels, a function that was diminished by the G209A mutation. However, mutant but not wild-type alpha-synuclein expression specifically enhanced dopamine associated oxidative damage. Non-expressing cells treated with reserpine to inhibit the vesicular monoamine compartmentalisation produced similar results. However, consistent with the hypothesis that mutant alpha-synuclein disrupts vesicular dopamine compartmentalization, this effect was diminished in cells expressing mutant alpha-synuclein. This may result in increased dopamine metabolism and cause selective oxidative damage to dopaminergic cells.

Aconitate Hydratase↗

[Does nCPAP-therapy change the lung function of patients with obstructive sleep apnea syndrome?].

BACKGROUND: nCPAP-therapy is standard for patients with obstructive sleep apnea syndrome (OSAS). This study investigated, if nCPAP changed the patients lung function. PATIENTS AND METHODS: Lung function of 228 OSAS patients without co-prevalent lung disease, who received nCPAP for the first time, was examined (whole body plethysmography, spirometry, and blood gas analysis). After 1, 2, and 3 years the results of the re-examined patients were compared with their individual starting results. RESULTS: The results of the patients in the basic and in the follow-up examinations was within standard range. During reexamination, an improvement of inspiratory vital capacity was registered repetitively, especially in smokers. On the other hand, MEF 50 decreased within the first two years and FEV (1) %VC, but not FEV (1), decreased after 2 and 3 years of reexamination. CONCLUSIONS: Neither obstructive nor restrictive lung diseases were diagnosed under nCPAP-therapy within three years. This study with a retrospective design showed significant improvements of vital capacity (VC) in patients with OSAS, especially in smokers, under nCPAP-therapy. This increase can be explained by an effect of practice in the examination and by recruitment of formerly hypoventilated lung areas. As MEF 50 and FEV (1) %VC depend on VC, the decrease of both parameters may be caused by the increase of VC. In summary, nCPAP did not cause negative effects of lung function in the investigated patients over a period of 3 years.

Continuous Positive Airway Pressure↗

Non-invasive ventilation in chronic obstructive pulmonary disease.

Non-invasive ventilation (NIV) via nasal or full face mask can be applied in respiratory failure due to chronic obstructive pulmonary disease (COPD) both in the acute and long-term settings. In acute exacerbation of COPD with respiratory failure it may be considered as a standard treatment. There is strong evidence that NIV might reduce intubation, complication, and mortality rate in patients with acute hypercapnia (PaCO(2) >45 mmHg). The method is cost effective and reduces hospital stay. NIV might be also useful in the weaning of COPD patients from invasive ventilation. On the other hand, for severe stable disease the data concerning a positive effect of NIV are less convincing. Preliminary evidence suggests that NIV improves gas exchange, sleep quality and quality of life and might reduce the need for hospitalization. Especially, COPD patients with substantial chronic hypercapnia (PaCO(2) >55 mmHg) and/or nocturnal hypoventilation, and those with repeated exacerbations may profit from NIV. In any case, NIV is a very valuable and effective tool in the non-pharmacological treatment of COPD. Every clinician who is involved in the management of COPD patients with respiratory insufficiency should be able to apply this technique.

Humans↗

Alpha-synuclein expression in HEK293 cells enhances the mitochondrial sensitivity to rotenone.

Mitochondrial dysfunction has been implicated in the aetiology of sporadic Parkinson's disease but its role in the disease mechanism is not clear. We have investigated the short term effect of G209A mutant or wild-type alpha-synuclein expression upon mitochondrial function using stable inducible cell models. Mitochondrial respiratory chain activities and membrane potential were normal suggesting that increased wild-type or mutant alpha-synuclein expression did not directly affect these parameters. However, both wild-type and mutant G209A alpha-synuclein expression enhanced the fall in mitochondrial membrane potential induced by the complex I inhibitor rotenone. This suggests an indirect interaction between alpha-synuclein expression and mitochondrial function which could render the mitochondria more vulnerable to inhibition by potential endogenous or exogenous factors found in dopaminergic neurones.

Cell Line↗

Effect of acid maltase deficiency on the endosomal/lysosomal system and glucose transporter 4.

Membrane bound glycogen storage in muscle is characteristic for the lysosomal storage disorder acid maltase (acid alpha-glucosidase) deficiency while in phosphofructokinase and phosphorylase deficiency, glycogen is stored free in the cytoplasm. Using immunohistochemistry, we examined whether acid maltase deficiency had an effect on early endosomes, recycling endosomes and trans-Golgi network, vesicle systems linked to lysosomes. Vacuolated glycogen containing fibres stained intensely for the lysosomal marker lysosomal-membrane-protein-1 within fibres and at the sarcolemma. There was a similar increase in immunoreactivity for markers of early endosomes (rab5), recycling endosomes (transferrin receptor) and the trans-Golgi network. In acid maltase deficiency, but not in normal muscle or other glycogenoses, staining for the insulin responsive glucose transporter 4 was markedly increased and partially co-localised with all vesicular markers. Our results suggest an effect of acid maltase deficiency extending to various vesicle systems linked to lysosomes. The enzyme defect may also affect the homoeostasis of receptors cycling through these organelles such as glucose transporter 4.

Adult↗

The variability of intracortical inhibition and facilitation.

OBJECTIVE: To assess the variability of transcranial magnetic stimulation paired pulse measurements of cortical excitability between subjects, between sessions and within subjects within sessions. METHODS: In experiment 1, intracortical inhibition and facilitation were assessed with a fixed conditioning stimulus intensity (CSI) of 80% of active motor threshold (AMT) whereas in experiment 2, the effect of different CSIs (60-110% of AMT) was investigated. RESULTS: Experiment 1 revealed that subjects differed significantly in the degree of inhibition and facilitation. Between sessions the variability was substantial as predicted by high within session variability. Experiment 2 allowed determination of individual thresholds for inhibition and facilitation. These thresholds were the best predictor of the amount of inhibition or facilitation at a given CSI. Across subjects we observed a high correlation of the threshold for inhibition (expressed in terms of maximum stimulator output) with AMT (r=0.93). Results for facilitation were more variable. CONCLUSIONS: The variability was high if a single CSI was used to compare the percent intracortical inhibition or facilitation between subjects, or between sessions. Much less variable was the threshold for intracortical inhibition/facilitation, which was highly correlated to AMT. We suggest that the ratio of CSI:AMT is a robust and useful additional measure of the integrity of neuronal circuits underlying intracortical inhibition/facilitation.

Adult↗

Inclusion formation in Huntington's disease R6/2 mouse muscle cultures.

Huntington's disease (HD) is an autosomal dominant disorder caused by an expansion in the number of glutamine repeats in the N-terminal region of the huntingtin protein. Nuclear and cytoplasmic aggregates of the N-terminal portion of huntingtin have been found in the brains of HD patients and the brains and non-neuronal tissues of the R6/2 HD transgenic mouse. We have cultured myoblasts and myotubes from transgenic R6/2 mice and littermate controls to investigate the formation of these inclusions in post mitotic cells. Huntingtin immunoreactivity was intense in differentiating, desmin positive myoblasts and myotubes from both control and R6/2 mice suggesting that it may play a role in myotube differentiation. Following differentiation huntingtin and ubiquitin positive aggregates were observed in R6/2 but not control cultures. After 3 weeks in differentiation medium cytoplasmic huntingtin and ubiquitin immunoreactive aggregates were observed in non-myotube cells, while nuclear huntingtin aggregates were seen in a proportion of myotubes after 6 weeks. Growth in the absence of serum resulted in a marked increase in the number of R6/2 myotubes containing nuclear inclusions after 6 weeks demonstrating that environmental factors influenced huntingtin aggregate formation in these cells. Consequently, cultured myotubes from R6/2 mice may be a useful post mitotic cell culture model to study both the biochemical consequences of huntingtin aggregates and the factors that may influence aggregate formation.

Animals↗

[Virtual multislice-CT-bronchoscopy as a diagnostic tool in patients with endobronchial tumors: case report of a carcinoid tumor].

BACKGROUND: Bronchial carcinoids are rare neuroendocrine tumors of the lung. Diagnosis is established by computed tomography (CT) and bronchoscopy-guided biopsy. Imaging features of carcinoids are highly characteristic including contrast enhancement and central intraluminal growth. Multislice-CT generated three-dimensional virtual bronchoscopy enables non-invasive and detailed view of the tracheobronchial system. CASE REPORT: A 70-year-old male with known silicosis and chronic cough with hemoptysis showed hypertransparency of the left lung on conventional images. Axial CT scans revealed a solid tumor in the left lower lobe. Virtual CT-bronchoscopy based on surface rendering depicted an intraluminal mass occluding the bronchus of the anterobasal segment that was confirmed by conventional endoscopy. Conventional and virtual bronchoscopy showed almost identical imaging features. Histopathological evaluation of the bioptic specimen revealed a typical carcinoid tumor. The patient successfully underwent resection of the left lower lobe with mediastinal lymphadenectomy. CONCLUSIONS: Virtual Multislice-CT-bronchoscopy can add important information about an intraluminal tumor and its relation to surrounding structures. Further studies have to be undertaken to evaluate the potentials of this promising method as a tool to determine endoluminal growth in tumorous lung lesions.

Aged↗

[Accidents caused by sleepiness--prediction by neurophysiologic/psychologic testing and simulated driving studies].

Daytime sleepiness is a leading symptom of various diseases, and is an important cause of accidents at the workplace and on the road. For the evaluation of accident frequency, the medical history, neurophysiological and neuropsychological tests, and driving simulator performance are applied. The present paper describes these different methods, and assesses their value in predicting accidents. In the last resort, no single test suffices to evaluate the accident risk of patients suffering from daytime sleepiness--rather, a combination of the methods described is needed, in particular when an expert opinion on a patient's ability to drive is required. To date, no controlled studies have been done to compare the predictive value of the methods considered herein. Our results suggest that the nearness of driving simulation to reality makes it a suitable additional test method, in particular for the monitoring of results under treatment.

Accidents, Traffic↗

Tuberculous involvement of the oesophagus with oesophagobroncheal fistula.

Tuberculous involvement of the oesophagus is a rare disease. Even if it is suspected, diagnosis is often difficult though dysphagia and chest pain are the most common symptoms without any other specific signs of tuberculosis. The diagnosis is based on oesophagography, oesophagoscopy, bronchoscopy, and computed tomographic scan. Suspected tuberculosis can be confirmed with histology, smear, and culture. The two most common differential diagnoses are Crohn's disease and carcinoma. The case is reported of a female patient with tuberculous involvement of the oesophagus, who developed an oesophagobroncheal fistula during steroid treatment started for suspicion of Crohn's disease. The patient was immunocompromised due to treatment with azathioprine that she was receiving for multiple sclerosis. The fistula was successfully treated by antituberculous chemotherapy alone.

Adult↗

[Estimation of accident risk in obstructive sleep apnea syndrome (OSAS) by driving simulation].

Abstract. Patients with obstructive sleep apnea syndrome (OSAS) have an accident rate between two and seven times higher than normals. Investigations on accident frequency are based on case history, insurancy reports, and driving simulator investigations. The present controlled study was planned to test whether an increased accident risk could be demonstrated in patients with OSAS before and on CPAP (continuous positive airway pressure)-therapy using the driving simulator C.A.R. Driving simulator performance was investigated in 31 patients with polysomnographically confirmed OSAS (apnea-hypopnea-index 24.8 +/- 21.5/h) before, 2 and 42 days after initiation of CPAP and was compared to 10 healthy controls in whom OSAS was excluded by polysomnography. Driving simulator performance was significantly worse in OSAS as compared to normals especially in terms of accident frequency (OSAS: 2.7 +/- 2.0, controls: 1.3 +/- 1.5, p < 0.05) and concentration faults (OSAS: 12.4 +/- 5.1, controls: 7.1 +/- 3.2, p < 0.01). On CPAP accident frequency (OSAS before therapy: 12.4 +/- 5.1, 2 days CPAP: 1.5 +/- 1.4, p < 0.01; 42 days CPAP: 0.9 +/- 1.3, p < 0.001) and frequency of concentration faults (OSAS before therapy: 12.4 +/- 5.1, 2 days CPAP: 6.5 +/- 3.9, p < 0.001; 42 days CPAP: 4.9 +/- 3.3, p < 0.001) could be lowered significantly both in the short and medium term of therapy. The driving simulator C.A.R. is an adequate tool for the evaluation of an increased accident risk in OSAS-patients and demonstrates the efficiency of CPAP-therapy.

Accidents, Traffic↗

[Inflammatory pseudopapilloma after recurring aspiration of fruit stones as rare differential diagnosis of bronchogenic cancer].

We present the case of a 51-year old man with drug-resistant pneumonia in the upper right lobe, weight loss and a 50-pack year history of cigarette smoking who underwent bronchoscopy. By clinical and radiological findings bronchogenic cancer was assumed. Fiberbronchoscopy showed an exophytic tumor-like mass obliterating the right upper lobe. Biopsies revealed an epithelial pseudopapillomatous tumor with multiple mucosal dysplasia and metaplasia. A second bronchoscopy in order to remove the lesion revealed a foreign body embedded in the tissue which could be removed easily. The foreign body proved to be a cherry stone, after its removal pneumonia resolved completely. In the same patient this lesion was recurrent one year later after aspiration of a grape seed. We present this case to emphasize the relationship between foreign body aspiration and inflammatory pseudopapilloma as a sequela of the inflammatory insult provoked by foreign bodies. Bronchoscopy is mandatory and may obviate misdiagnosis and thoracotomy. The use of inhaled and systemic steroids can be used to facilitate successful endoscopic extraction.

Carcinoma, Bronchogenic↗

Investigations of the dynamic behaviour of the composition of combined sewage using on-line analyzers.

Continuously analyzing sensors today permit the recording of the dynamic behaviour pattern of pollutants in combined sewage through physical parameters. This report presents the results of such measurements. They were done in a storm water tank which is equipped with a combined sewage overflow and located at the end of a 360 ha catchment area. The results show that by using a combination of sensors for dissolved solids (using UV absorption) and of sensors for particulate solids (using scattered light measurement), reliable information on the composition of the combined sewage can be obtained. A statistical relationship between these two parameters and the chemical oxygen demand was established. The analyzing methods presented permit the real-time control of sewer systems on the basis of the pollution carried in the combined sewage. Through the information on the actual concentration of primary pollutants provided by on-line analysis, heavily polluted streams can be retained selectively in storm water tanks or directed to the treatment plant. However, due to the adverse conditions in a sewer system operational disturbances and stringent maintenance requirements are still an impediment to long-term operation.

Computer Systems↗

Surgery required to verify atypical mycobacterial infections.

To estimate the incidence and distribution of nontuberculuous mycobacterial surgery, a retrospective case record study of 42 children operated for cervicofacial atypical mycobacterial infections in Oslo from 1990 to 2000 was performed. Mean age at diagnosis was 41 months and mean duration of the disease was 40 weeks from symptom onset to remission. All presented with localized and unilateral disease without increased hematological parameters. The majority of children had one lesion localized in the submandibular region characterized by changes in the overlying skin color, but without necrosis or fistula formation. Children below three significantly more often presented with only one lesion and the referring physician more frequently suspected neoplasm and bacterial adenitis than reactive adenopathy in this group. Compared to older children, there was a tendency for shorter symptom duration prior to outpatient treatment (mean 4 and 13 weeks for children up to 3 and above 3 years, respectively, t=-1.6, P=0.11). Furthermore, mycobacterial cultures and histopathology from surgical specimens was needed to diagnose the disease correctly. Fine-needle aspiration biopsy was unsuccessful in 27% (n=8) of the patients, due to non-cooperative patients (n=2) or inconclusive material (n=6), and mycobacterial growth was not obtained in any of the samples. Intradermal mycobacteria skin testing yielded 29% (n=10) false negatives. Although mycobacteria was correctly diagnosed in the remaining patients, correct specimen was found in only 31% (n=11) of the 25 cases.

Child↗

Orthonitridoborate ions [BN3]6- in oxonitridosilicate cages: synthesis, crystal structure, and magnetic properties of Ba4Pr7[Si12N23O][BN3], Ba4Nd7[Si12N23O][BN3], and Ba4Sm7[Si12N23O][BN3].

The isotypic title compounds Ba4Pr7[Si12N23O][BN3], Ba4Nd7[Si12N23O][BN3], and Ba4Sm7[Si12N23O][BN3] were prepared by reaction of Pr, Nd, or Sm, with barium, BaCO3, Si(NH)2, and poly(boron amide imide) in nitrogen atmosphere in tungsten crucibles using a radiofrequency furnace at temperatures up to 1650 C. They were obtained as main products (approximately 70%) embedded in a very hard glass matrix in the form of intense dark green (Pr), orange-brown (Sm), or dark red (Nd) large single crystals, respectively. The stoichiometric composition of Ba4Sm7[Si12N23O][BN3] was verified by a quantitative elemental analysis. According to the single-crystal X-ray structure determinations (Ba4Ln7[Si12N23][BN3], Z= , P6 with Ln = Pr: a = 1225.7(1), c = 544.83(9) pm, R1 = 0.013, wR2 = 0.030; Ln = Nd: a = 1222.6(1), c = 544.6(1) pm, R1 = 0.017, wR2 = .039; Ln = Sm: a = 1215.97(5), c = 542.80(5) pm, R1 = 0.047, wR2 = 0.099) all three compounds are built up by a framework structure [Si12N23O]23- of corner-sharing SiX4 tetrahedrons (X = O, N). The oxygen atoms are randomly distributed over the X positions. The trigonal-planar orthonitridoborate ions [BN3]6- and also the Ln(3)3+ are situated in hexagonal cages of the framework (bond lengths Si-(N/O) 169-179 pm for Ln=Pr). The remaining Ba2+ and Ln3- ions are positioned in channels of the large-pored network. The trigonal-planar [BN3]6- ions have a B-N distance of 147.1(6) pm (for Ln = Pr). Temperature-dependent susceptibility measurements for Ba4Nd7[Si12N23O][BN3] revealed Curie-Weiss behavior above 60 K with an experimental magnetic moment of muexp = 3.36(5) microB/Nd. The deviation from Curie-Weiss behavior below 60 K may be attributed to crystal field splitting of the J = 9/2 ground state of the Nd3+ ions. No magnetic ordering is evident down to 4.2 K.

Journal Article↗