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Biomedical subjects

M Orth

Publications and source records attributed to M Orth.

At least 55 records · Page 3Linked to original sources
PubMed2001

Mitochondria and degenerative disorders.

In mammalian cells, mitochondria provide energy from aerobic metabolism. They play an important regulatory role in apoptosis, produce and detoxify free radicals, and serve as a cellular calcium buffer. Neurodegenerative disorders involving mitochondria can be divided into those caused by oxidative phosphorylation (OXPHOS) abnormalities either due to mitochondrial DNA (mtDNA) abnormalities, e.g., chronic external ophthalmoplegia, or due to nuclear mutations of OXPHOS proteins, e.g., complex I and II associated with Leigh syndrome. There are diseases caused by nuclear genes encoding non-OXPHOS mitochondrial proteins, such as frataxin in Friedreich ataxia (which is likely to play an important role in mitochondrial-cytosolic iron cycling), paraplegin (possibly a mitochondrial ATP-dependent zinc metalloprotease of the AAA-ATPases in hereditary spastic paraparesis), and possibly Wilson disease protein (an abnormal copper transporting ATP-dependent P-type ATPase associated with Wilson disease). Huntingon disease is an example of diseases with OXPHOS defects associated with mutations of nuclear genes encoding non-mitochondrial proteins such as huntingtin. There are also disorders with evidence of mitochondrial involvement that cannot as yet be assigned. These include Parkinson disease (where a complex I defect is described and free radicals are generated from dopamine metabolism), amyotrophic lateral sclerosis, and Alzheimer disease, where there is evidence to suggest mitochondrial involvement perhaps secondary to other abnormalities.

Adenosine Triphosphatases↗
PubMed2001

Shed L-selectin (sCD62L) load in trauma patients.

BACKGROUND: Low circulating plasma concentrations of the leukocyte adhesion molecule L-selectin (sCD62L) were found to be associated with an increased risk for subsequent lung failure and case fatality after severe trauma. The objective of this study was to determine the robustness of soluble L-selectin, correcting for a broad spectrum of physiological variables. METHODS: Patients with suspected multiple and/or trunk injuries were enrolled into this study over a 1-year period. Plasma samples were obtained on hospital presentation, and circulating soluble L-selectin was measured with a commercially available ELISA kit. Study records comprised all relevant clinical and laboratory data. Thirty-day survival rate, subsequent acute lung failure, and nosocomial pneumonia were defined as study endpoints. Statistical analysis was performed using multivariate logistic regression models. RESULTS: Seventy patients with a mean age of 35.51 years (range, 10-87 years) and a mean ISS score of 36.61 (95% CI, 31.08-42.14) entered the study. Eleven patients died, leading to an attributable mortality of 15.70%. L-Selectin levels did not differ between survivors and nonsurvivors. Five patients progressed to acute lung injury, whereas 11 patients developed hospital-acquired pneumonia. Lower L-selectin levels indicated patients at risk for lung injury with a relative odds estimated at 4.43 (P = 0.017). Statistical significance diminished in the multivariate model. In contrast, plasma concentrations of circulating sCD62L were significantly decreased in patients developing nosocomial pneumonia (P = 0.023), with a twofold increased relative odds (OR, 1.96; 95% CI, 0.51-7.50). No effect modification was observed by the included covariables. CONCLUSIONS: The results of this study highlight the independent predictive value of initially decreased soluble L-selectin levels for the identification of patients susceptible to subsequent respiratory complications after severe trauma.

Adolescent↗
PubMed2001

[Obstructive sleep apnea syndrome: a cardiovascular risk factor?].

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is frequently associated with cardiovascular disease. We investigated endothelium-dependent and endothelium-independent nitric oxide-mediated vasodilatory function in normotensive patients with OSAS using the hand vein compliance technique. PATIENTS AND METHODS: Dose-response curves to the endothelium-dependent vasodilator bradykinin were obtained in 23 male subjects with OSAS and 12 male control subjects of comparable age, height, and weight. RESULTS: Mean (+/- SD) maximum dilation (Emax) to bradykinin was significantly lower in OSAS patients than in controls (59.8 +/- 26.0 vs. 94.8 +/- 9.5%, p < 0.0001). Mean vasodilation with nitroglycerin was not diminished in the OSAS group (90.7 +/- 30.5 vs. 100.3 +/- 12.9% in controls; n.s.). In 11 OSAS patients, a follow-up investigation was performed after at least 2 months of treatment with nasal continuous positive airway pressure (CPAP): Emax to bradykinin rose from 54.5 +/- 19.2% to 111.5 +/- 25.1% after treatment (p < 0.001). Mean vasodilation to nitroglycerin was unchanged. CONCLUSIONS: These results suggest that endothelium-dependent nitric oxide-mediated vasodilation is impaired in patients with OSAS due to an impaired function in the endothelial cells. This impairment is reversible with CPAP treatment.

Bradykinin↗
PubMed2001

An improved method for the rapid assessment of persisting chylomicron remnant concentrations.

Persisting chylomicron remnant concentrations have been linked to premature atherosclerosis. The analysis of persisting chylomicron remnant concentrations by an oral triglyceride tolerance test, however, is time-consuming for the study subjects and requires large resources in the laboratory. Therefore, only small numbers of subjects have been studied in the past. We describe major improvements of the testing procedure in regard of composition of the fatty meal, of patient testing, and measurement of postprandial remnants. Shifting the time of the (ready-to-use) fatty drink from the morning hours to bedtime was well accepted by the study subjects and allowed the analysis of blood samples drawn at the morning with minimal impact on the participants' time and with minimal interferences by confounding factors (e.g. smoking, additional food intake, physical activity). Chylomicron remnants were measured by fluorometry of the supernatant after ultracentrifugation. This procedure was sensitive, was specific for chylomicron remnants, and was easy to perform. The biological validity of the improved procedure was evaluated by studying type III hyperlipoproteinemia patients and normolipemic apolipoprotein (Apo) E2 homozygotes. In conclusion, this improved test permits the rapid testing for persisting chylomicron remnants in the clinical routine and in large epidemiological studies.

Adult↗
PubMed2001

Respiratory monitoring in neuromuscular disease - capnography as an additional tool?

Daytime complaints like fatigue, sleepiness and cognitive dysfunction in neuromuscular disease can be due to nocturnal hypercapnia and hypoxemia. Daytime respiratory diagnostics does not reflect sleep disordered breathing. Nocturnal pulse oxymetry and capnography were performed in 11 patients (15-75 years old) with different slowly progressive neuromuscular diseases. Only four patients complained of dyspnea. Pulmonary function was abnormal in three patients. Blood gas samples showed a hypoxemia in three patients. Pulse oxymetry results were pathological in six patients. Nine patients presented abnormal capnographies. According to these results either nocturnal oxygen application was initiated or ventilatory parameters were modified. Daytime symptoms and muscular strength improved markedly. Capnography and pulse oxymetry should be performed during the course of neuromuscular disease to detect respiratory insufficiency. Capnography seems to be a more sensitive indicator for respiratory impairment especially when artificial ventilation has been initiated.

Adolescent↗
PubMed2001

[The impact of different definitions of hypoxemia on the relation between awake pulmonary pressure and hypoxemia during sleep in patients with COPD].

BACKGROUND: Sleep related hypoxemia (SRH) in chronic obstructive pulmonary disease (COPD) can be easily detected by pulse-oximetry and may contribute to the development of pulmonary hypertension (PH). Since several parameters for the quantification of SRH are in use, we investigated which of these parameters has the strongest relation to the awake pulmonary arterial pressure (PAP) and is able to distinguish between patients without and with PH. PATIENTS AND METHODS: 44 COPD-patients (awake PaO2 > or = 60 mm Hg) were investigated. PAP at rest (PAP; pathological threshold > 20 mm Hg) and under physical exercise (PAPB; p.t. > 28 mm Hg) were determined during daytime by Swan-Ganz-catheter. To quantify the degree of SRH the following parameters of nocturnal pulse-oximetry were used: mean nocturnal oxygen saturation (SaO2 m; p.t. < 90%), nadir SaO2 (SaO2 min; p.t. < 85%), and mean time of SaO2 < or = 90% in relation to total time of registration (t90; p.t. > 30%). Linear correlations and regressions as Chi 2-respectively Fisher-test were used for statistical analysis (p < 0.05). RESULTS: Generally there was only a weak relation between PAP and SRH. The best linear correlation at rest respectively under physical exercise was found between PAP and SaO2 min (r = -0.529 resp. -0.541, p < 0.001). Using the above defined thresholds for PAP and SaO2 patients could be most precisely separated into those without and with PH using SaO2 min with a threshold for the pathological range of < 85% (p = 0.030 resp. 0.002). t90 with a threshold > 30%, however, had a much worse selectivity (p = 0.487 resp. 0.057). CONCLUSIONS: In COPD-patients with SRH the closest relation can be found between nadir SaO2 and PAP resp. PAPB. Furthermore nadir SaO2 (< 85%) could more precisely separate patients into those without and with pulmonary hypertension than t90. The overall weak relation between nocturnal oxygenation and pulmonary hypertension shows, however, that other factors such as daytime PaO2, hypercapnia or emphysema are involved in the development of pulmonary hypertension in COPD.

Blood Pressure↗
PubMed2001

Daily access to pasture turnout prevents loss of mineral in the third metacarpus of Arabian weanlings.

Seventeen Arabian weanlings were used to determine the influence of housing on third metacarpal bone mass. Animals were separated into three treatment groups: Pasture (n = 6), Stall (n = 5), and Partial-Pasture (n = 6). Radiographs of the left third metacarpus were taken every 28 d to determine radiographic bone aluminum equivalence (RBAE). Serum was collected every 14 d and analyzed for osteocalcin, carboxyterminal telopeptide of type I collagen (ICTP), and keratan sulfate. Hip and wither height, BW, and cannon circumference were measured every 28 d. Lateral RBAE in the pastured group increased linearly from d 0 to d 56 (P = 0.001). In the Pasture group, total RBAE increased from d 0 to 56 (P = 0.05) and medial RBAE tended to increase from d 0 to d 28 (P = 0.06). The Partial Pasture group increased from d 0 to 56 in medial (P = 0.02) and tended to increase in total RBAE (P = 0.08). Although the Stall group demonstrated an increase in total RBAE from d 0 to 56 (P = 0.04), the Partial Pasture group tended to have greater total RBAE than the Stall group at d 28 (P = 0.08), and the Pasture group had greater lateral RBAE at d 28 (P = 0.005) and 56 (P = 0.007) than did the Stall group. At d 28, medial RBAE was greater in the Pasture (P = 0.003) and Partial Pasture (P = 0.05) groups than in the Stall group. Pasture and Stall groups tended to decrease in osteocalcin (P = 0.06), whereas Partial Pasture weanlings decreased (P = 0.01) from d 0 to 56. All treatment groups decreased from d 0 to 56 in ICTP (P < 0.01). Pastured weanlings decreased from d 0 to 42 in serum keratin sulfate (P < 0.05), whereas the Stall group decreased from d 0 to 56 (P = 0.05). All treatment groups increased in wither height (P < or = 0.01), hip height (P < or = 0.001), and BW (P < or = 0.01). Both the Pasture and Partial Pasture weanlings demonstrated greater cannon circumference than Stall weanlings on d 28 (P < or = 0.05) and 56 (P < or = 0.005). These data demonstrate that pasture rearing or 12-h daily turnout is beneficial to maintaining and increasing bone mineral content in weanling Arabian horses.

Animal Nutritional Physiological Phenomena↗
PubMed2000

Expression of mutant alpha-synuclein causes increased susceptibility to dopamine toxicity.

Mutations of the alpha-synuclein gene have been identified in autosomal dominant Parkinson's disease (PD). Transgenic mice overexpressing wild-type human alpha-synuclein develop motor impairments, intraneuronal inclusions and loss of dopaminergic terminals in the striatum. To study the mechanism of action through which mutant alpha-synuclein toxicity is mediated, we have generated stable, inducible cell models expressing wild-type or PD-associated mutant (G209A) alpha-synuclein in human-derived HEK293 cells. Increased expression of either wild-type or mutant alpha-synuclein resulted in the formation of cytoplasmic aggregates which were associated with the vesicular (including monoaminergic) compartment. Expression of mutant alpha-synuclein induced a significant increase in sensitivity to dopamine toxicity compared with the wild-type protein expression. These results provide an explanation for the preferential dopaminergic neuronal degeneration seen in both the PD G209A mutant alpha-synuclein families and suggest that similar mechanisms may underlie or contribute to cell death in sporadic PD.

Blotting, Western↗
PubMed2000

Postprandial chylomicrons and VLDLs in severe hypertriacylglycerolemia are lowered more effectively than are chylomicron remnants after treatment with n-3 fatty acids.

BACKGROUND: n-3 Fatty acids lower plasma triacylglycerols not only in the fasting state but also in the postprandial state. However, it is not known whether chylomicrons, chylomicron remnants, and VLDLs are all affected equally or whether some lipoprotein species are lowered preferentially. OBJECTIVE: Lipoproteins, including large and small chylomicron remnants, were determined specifically with the aid of a newly developed method involving a combination of size-exclusion chromatography and fluorometric determination of retinyl palmitate, which served as a marker for exogenous fat. DESIGN: Twelve hypertriacylglycerolemic men were treated for 6 wk with 4 capsules containing 85% fish-oil concentrate/d; each capsule contained 850 mg n-3 fatty acid ethyl esters (49.1% eicosapentaenoic acid by wt and 32.2% docosahexaenoic acid by wt). Oral-fat-tolerance tests were performed before and after the treatment. Blood samples were drawn in the fasting state and until 8 h postprandially. RESULTS: Treatment with n-3 fatty acids reduced the fasting VLDL-triacylglycerol concentration by 44% (P < 0.05) and postprandial chylomicrons and VLDLs at 4, 6, and 8 h (P < 0.05) by 49-64% and 36-43%, respectively. Chylomicron remnants were reduced only in the late postprandial phase: large chylomicron remnants by 19% at 6 h and by 43% at 8 h (P < 0.05) and small chylomicron remnants by 31% at 8 h (P < 0.05). CONCLUSION: n-3 Fatty acids effectively lower chylomicrons and VLDLs, but their effect on chylomicron remnants was observed only in the late postprandial phase.

Adult↗
PubMed2000

[Enantiomeric monoterpenes in ether oil from Achillea millefolium s. I.--a taxonomically useful marker?].

The Achillea millefolium complex is a group of taxonomically hardly separable species. Yarrow has the tendency to hybridize and to vary in phenotype. An obvious characterization of the species or hybrids is not just important for the taxonomical distinction but also for a reliable assessment of herbal drug quality. Most of the Achillea plants are still gathered from natural populations. According to the variation in phenotype, mixtures with Achillea species, which contain allergy setting compounds, often cannot be determined. Morphometric investigations exclusively do not replace a further chemical characterization. Therefore we tried to assess the composition of the chiral monoterpenes alpha-pinene, beta-pinene and sabinene. They were selected because of their frequency in the essential oil of Achillea species. By method of M.C.S.S. (Moving Capillary Stream Switching) the differentiation of stereoisomeres succeeded directly from the essential oil, which was distilled or extracted by headspace trapping at room temperature. The enantiomeric distribution neither depends on the method of extraction, nor on the habitat or the developmental stage of Yarrow. Since the compositions of enantiomeres from several Achillea species and their hybrides are of different pattern, it seemed to represent an additional marker. Though investigations of all species within the Achillea millefolium group and possibly of further chiral compounds are necessary to ensure these results.

Bicyclic Monoterpenes↗
PubMed1999

Hemostatic factors in hypertriglyceridemic men: effects of a fatty meal before and after triglyceride-lowering treatment with etofibrate.

The aims of this double-blind study were to examine whether in hypertriglyceridemic men the ingestion of a standardized fatty meal alters hemostasis negatively and whether triglyceride-lowering treatment with etofibrate for 6 weeks alters fasting and postprandial hemostasis positively, thus reversing the potential negative effects of a fatty meal on postprandial hemostasis. To answer these questions, we measured markers of hemostasis immediately before a standardized fatty meal, and 4, 6, 8, and 10 hours after the meal in 21 hypertriglyceridemic men both before and after treatment with etofibrate. We found that the concentration of plasmin alpha2antiplasmin complex markedly increased for at least 10 hours after the fatty meal, but that the activation of factor XII and the concentration of prothrombin activation fragment1+2 decreased after the fatty meal. These results on factor XII contradict reported in vitro data. Triglyceride-lowering treatment with etofibrate in 10 of these men for 6 weeks increased fasting and postprandial protein C and plasminogen and also slightly decreased the activation of fXII; however, it did not reverse the postprandial increase of PAP or change the decrease of prothrombin activation fragment1+2. Our findings indicate that postprandial lipoproteins alter markers of hemostasis positively in an antithrombotic and profibrinolytic direction. In addition, triglyceride-lowering treatment with etofibrate only slightly improves markers of fasting and postprandial hemostasis in an antithrombotic and profibrinolytic direction.

Clofibric Acid↗
PubMed1999

Expression of human apolipoprotein E3 or E4 in the brains of Apoe-/- mice: isoform-specific effects on neurodegeneration.

Apolipoprotein (apo) E isoforms are key determinants of susceptibility to Alzheimer's disease. The apoE4 isoform is the major known genetic risk factor for this disease and is also associated with poor outcome after acute head trauma or stroke. To test the hypothesis that apoE3, but not apoE4, protects against age-related and excitotoxin-induced neurodegeneration, we analyzed apoE knockout (Apoe-/-) mice expressing similar levels of human apoE3 or apoE4 in the brain under control of the neuron-specific enolase promoter. Neuronal apoE expression was widespread in the brains of these mice. Kainic acid-challenged wild-type or Apoe-/- mice had a significant loss of synaptophysin-positive presynaptic terminals and microtubule-associated protein 2-positive neuronal dendrites in the neocortex and hippocampus, and a disruption of neurofilament-positive axons in the hippocampus. Expression of apoE3, but not of apoE4, protected against this excitotoxin-induced neuronal damage. ApoE3, but not apoE4, also protected against the age-dependent neurodegeneration seen in Apoe-/- mice. These differences in the effects of apoE isoforms on neuronal integrity may relate to the increased risk of Alzheimer's disease and to the poor outcome after head trauma and stroke associated with apoE4 in humans.

Aging↗
PubMed1999

Effects of a frequent apolipoprotein E isoform, ApoE4Freiburg (Leu28-->Pro), on lipoproteins and the prevalence of coronary artery disease in whites.

Different isoforms of apoE modulate the concentrations of plasma lipoproteins and the risk for atherosclerosis. A novel apoE isoform, apoE4Freiburg, was detected in plasma by isoelectric focusing because its isoelectric point is slightly more acidic than that of apoE4. ApoE4Freiburg results from a base exchange in the APOE4 gene that causes the replacement of a leucine by a proline at position 28. Analysis of the allelic frequencies in whites in southwestern Germany revealed that this isoform is frequent among control subjects (10:4264 alleles) and is even more frequent in patients with coronary artery disease (21:2874 alleles; P=0.004; adjusted odds ratio, 3.09; 95% confidence interval, 1.20 to 7.97). ApoE4Freiburg affects serum lipoproteins by lowering cholesterol, apoB, and apoA-I compared with apoE4 (P<0.05). Our 4 apoE4Freiburg homozygotes suffered from various phenotypes of hyperlipoproteinemia (types IIa, IIb, IV, and V). In vitro binding studies excluded a binding defect of apoE4Freiburg, and in vivo studies excluded an abnormal accumulation of chylomicron remnants. ApoE4Freiburg and apoE4 accumulated to a similar extent in triglyceride-rich lipoproteins. HDLs, however, contained about 40% less apoE4Freiburg than apoE4. In conclusion, our data indicate that apoE4Freiburg exerts its possible atherogenic properties by affecting the metabolism of triglyceride-rich lipoproteins and HDL.

Adult↗
PubMed1999

[Intermittent positive pressure ventilation after sternectomy].

BACKGROUND: The indication for intermittent positive pressure ventilation (IPPV) is the symptomatic hypercapnic ventilatory insufficiency. Beside the improvement of life quality and extension of life time the aim of IPPV is a reduction of the secondary effects of chronic hypoventilation in order to stabilize the symptoms. PATIENTS AND METHODS: We examined 2 patients after sternectomy because of osteomyelitis who developed a symptomatic ventilatory insufficiency together with recurrent dys- and atelectasis and pneumonia, resistant against to antibiotic treatment. After initiation of IPPV the patients turned to a clinically stable condition. The nocturnal oxygen saturation improved as well as the daytime blood gas analysis. In these patients the indication for IPPV was not only the symptomatic hypercapnic ventilatory insufficiency but also the prophylaxis of recurrent dys- and atelectasis and pneumonia. Antibiotic therapy after sternectomy is often not successful, therefore in case of recurrent infections in patients with unstable thorax the early initiation of IPPV seems to be useful.

Aged↗