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Biomedical subjects

M Heiden

Publications and source records attributed to M Heiden.

At least 19 recordsLinked to original sources

Characterization of a laboratory model of computer mouse use - applications for studying risk factors for musculoskeletal disorders.

In the present study, we assessed the wrist kinetics (range of motion, mean position, velocity and mean power frequency in radial/ulnar deviation, flexion/extension, and pronation/supination) associated with performing a mouse-operated computerized task involving painting rectangles on a computer screen. Furthermore, we evaluated the effects of the painting task on subjective perception of fatigue and wrist position sense. The results showed that the painting task required constrained wrist movements, and repetitive movements of about the same magnitude as those performed in mouse-operated design tasks. In addition, the painting task induced a perception of muscle fatigue in the upper extremity (Borg CR-scale: 3.5, p<0.001) and caused a reduction in the position sense accuracy of the wrist (error before: 4.6 degrees , error after: 5.6 degrees , p<0.05). This standardized painting task appears suitable for studying relevant risk factors, and therefore it offers a potential for investigating the pathophysiological mechanisms behind musculoskeletal disorders related to computer mouse use.

Adult↗

Are quality differences responsible for different adverse reactions reported for SD-plasma from USA and Europe?

Thromboembolic adverse reactions reported after transfusion of SD-plasma in the United States (US) prompted us to perform a comparative study with SD-plasma from the US and the European (EU) market. In SD-plasma from US, residual tri-N-butyl phosphate was found, and citrate concentrations were lower than in EU-plasma. Except for substantial losses of FV, FVIII and antiplasmin found for all SD-plasmas, clotting factor activities were mainly retained. However, for SD-plasma from US, markedly elevated concentrations of lipoprotein (a) [Lp(a)], fibrin monomer and a particularly high degree of complement activation (C3a des-Arg) were observed. Furthermore, pronounced differences were found for protein S. Although SD-plasma pools from US contained nearly normal concentrations of free and bound protein S antigen, protein S activities were almost completely absent. In contrast to this, SD-plasma from EU showed a moderate loss of both protein S activity and free antigen. Antitrypsin inhibitor activities were much more diminished in SD-plasma from US than from EU. In view of a possible thrombogenicity of SD-plasma from US, the loss of protein S and elevated Lp(a) concentrations could be of significance. The very high levels of C3a des-Arg in US plasma could possibly have an additional effect, through priming platelet activation after transfusion.

Blood Coagulation Factors↗

Effects of time pressure and precision demands during computer mouse work on muscle oxygenation and position sense.

The present study investigated the effects of time pressure and precision demands during computer mouse work on muscle oxygenation and position sense in the upper extremity. Twenty-four healthy subjects (12 males and 12 females) performed a 45-min standardized mouse-operated computer task on two occasions. The task consisted of painting rectangles that were presented on the screen. On one occasion, time pressure and precision demands were imposed (more demanding task, MDT), whereas, on the other occasion, no such restraints were added (less demanding task, LDT). The order of the two task versions was randomized. Tissue oxygen saturation in the trapezius and extensor carpi radialis muscles was recorded throughout, and the position-matching ability of the wrist was measured before and after the tasks. In addition, measurements of autonomic nervous system reactivity and subjective ratings of tenseness and physical fatigue were obtained. Performance was measured in terms of the number of rectangles that were painted during the task. During MDT, oxygen saturation in extensor carpi radialis decreased (P < 0.05) compared to LDT. These data were paralleled by increased electrodermal activity (P < 0.05), skin blood flow (P < 0.05), ratings of tenseness and fatigue (P < 0.01), and increased performance (P < 0.01) during MDT. Females exhibited lower oxygen saturation than males, during rest as well as during the computer tasks (P < 0.01). Wrist repositioning error increased following LDT as compared to MDT (P < 0.05). In conclusion, computer mouse work under time pressure and precision demands caused a decrease in forearm muscle oxygenation, but did not affect wrist position sense accuracy. We attribute our changes in oxygenation more to increased oxygen consumption as a result of enhanced performance, than to vasoconstriction.

Adult↗

[Report on Notifications pursuant to Section 21 German Transfusion Act for 2001 and 2002].

The report pursuant to Section 21 German Transfusion Act is based on data referring to 4.53 and 4.66 million allogeneous whole blood donations and 1.35 and 1.89 million apheresis donations respectively for the years 2001 and 2002. Since 2000, the quantity of plasma for fractionation from apheresis has doubled to approx. 1 million litres in 2002. At the same time, the number of private apheresis facilities has also increased. The data on plasma for fractionation (both from whole blood and from apheresis) have shown a sharp increase for both report periods, mainly due to the rise in the quantity of plasma from apheresis. In spite of this, the quantity for plasma for fractionation available to the German market declined by 43% during the report period, due to increasing export figures. The data on the manufacture of blood components are reliable, since the notifications are almost complete. In 2001, 4.32 million transfusion units of erythrocyte concentrates, the most important product derived from whole blood donations, were manufactured, compared with 4.45 million in 2002, out of these, slightly less than 77 percent were manufactured in the blood donations services of the Red Cross. The consumption values reported were clearly below the figures for the manufacture, with 3.2 million transfusion units in 2001 and 3.5 million in 2002. However, some facilities of the health service did not meet the requirement to notify their figures. As far as the data on manufacture, imports and exports of plasma derivatives are concerned, further improvements are required because of the complexity of the matter and the various implications to be taken into account. However, a statement on the supply situation cannot be yet made anyway, due to the missing notifications on the consumption figures.

Blood Component Removal↗

Plasma quality after whole-blood filtration depends on storage temperature and filter type.

The study evaluated the quality of plasma obtained after whole-blood filtration with four different polyester filters and one polyurethane filter. The activities of coagulation factors and proteinase inhibitors were not or only negligibly affected by filtration, in all experiments. Filtration did not increase markers of clotting and fibrinolysis. Only a strong neutrophil and complement activation was observed, which depended on the type of filter and whole-blood storage conditions. However, as neutrophil elastase-specific degradation products did not increase and the complement-derived anaphylatoxin C3a was found in its inactivated form, C3a-desArg, these filtration-dependent changes apparently have little impact on the therapeutic quality of whole-blood-filtered fresh frozen plasma for transfusion.

Antithrombins↗

[Additive retrobulbar anesthesia in surgery of retinal detachment with general anesthesia. Reduced postoperative pain and stress response].

BACKGROUND: It has recently been shown that the pain occurring after retinal detachment surgery can be reduced by combined general and retrobulbar anesthesia. This study investigated the effect of retrobulbar anesthesia on the intra- and postoperative stress response and on postoperative pain, vigilance, nausea and vomiting. PATIENTS AND METHODS: In this prospective randomized study, 45 patients were enrolled where scleral buckling surgery for retinal detachment had been performed under general anesthesia. Bupivacain 0.5% (4 ml) was injected retrobulbarly in group I (n = 15) before surgery (preoperative) and in group II (n = 15) after surgery (postoperative), group III did not receive retrobulbar anesthesia. At different times during and after surgery, blood pressure, cortisol and glucose levels, time in the recovery unit, vigilance score, nausea and vomiting were measured and the pain score was determined. The dosages of intraoperative opioid analgetics and of postoperative pain medication were documented. RESULTS: Retrobulbar anesthesia reduces postoperative pain. Intra- and postoperative endogenous stress responses in groups I and II were reduced and the plasma levels of cortisol and glucose in group I were lower than in group II. In group I, nausea, dosages of intraoperative opioid analgetics and postoperative pain medication were reduced, the vigilance was increased and time in the recovery unit was shortened. CONCLUSIONS: The data show that combined local and general anesthesia has several advantages over general anesthesia alone, especially when the retrobulbar injection is given before retinal detachment surgery.

Aged↗

Transition from suspension to adherent growth is accompanied by tissue factor expression and matrix metalloproteinase secretion in a small cell lung cancer cell line.

Small cell lung cancer (SCLC) is a very malignant tumor known to grow aggressively and to metastasize early. It is well established that metastasis generally involves both tumor cell adhesion and proteolytic degradation of the extracellular matrix. However, SCLC cells cultured in vitro, such as the classic SCLC cell line NCI-H69, grow in floating aggregates and express only negligible proteolytic activity. In this report, we show that NCI-H69 cells can be selected for adherent growth. In contrast to parental suspension cells, the adherent cells were found to express tissue factor as well as gelatinolytic activity, attributable to matrix metalloproteinases 2 and 9. Such a switch of tumor cell characteristics, if it could occur in SCLC patients, might add to the understanding of the steps involved in the spreading of this highly metastatic type of lung cancer.

Carcinoma, Small Cell↗

Intramuscular pressure and electromyographic responses of the vastus lateralis muscle during repeated maximal isokinetic knee extensions.

The purpose of the study was to investigate changes in intramuscular pressure (IMP) (maximal during contraction - peak IMP, and between contraction, relaxation IMP - RxIMP) and surface electromyographic activity (EMG) parameters [mean frequency of the power spectrum (fmean), and signal amplitude, root mean square (RMS)] throughout 100 repetitive isokinetic contractions for six healthy subjects. Parameters were recorded simultaneously from the vastus lateralis muscle during maximal knee extension. Regression analyses revealed significant decreases for peak IMP and fmean, and an increase in RxIMP; RMS, however, did not change. All parameters demonstrated trends of change throughout the contractions that were non-linear. Details and inter relations for RxIMP and fmean were highlighted to express intramuscular fluid accumulation and fatigue development, respectively. Individual regression analyses for RxIMP revealed significant positive correlations for all subjects (range of r=0.62 to 0.89). At group level, mean RxIMP increased from 6.0 mmHg for the 1st contraction to 14.0 mmHg for the 100th contraction. For fmean, individual regressions were significantly negative for all subjects (r=-0.75 to -0.89). Fmean decreased from 89.2 Hz for the 1st contraction to 63.3 Hz for the 100th contraction. When the data were delineated between the fatigue (contractions 1-40) and endurance phases (41-100), the slopes of increase for RxIMP, and of decrease for fmean were significantly greater during the fatigue phase. RxIMP throughout the 100 contractions correlated negatively with fmean for each subject (r=-0.54 to -0.78); when delineated, the correlation between parameters was significantly greater for the fatigue as compared with the endurance phase. Relaxation IMP trends are mainly attributed to intramuscular water accumulations during repetitive contractions. In spite of consistent correlations between RxIMP and fmean a causal association could not be established. It may be suggested that a common factor occurring during the fatiguing process governs changes in RxIMP and fmean.

Adult↗

Tyrosine hydroxylase polymorphism and phenotypic heterogeneity in bipolar affective disorder: a multicenter association study.

Tyrosine hydroxylase (TH), the rate-limiting enzyme in the metabolism of catecholamines, is considered a candidate gene in bipolar affective disorder (BPAD) and has been the subject of numerous linkage and association studies. Taken together, most results do not support a major gene effect for the TH gene in BPAD. Genetic and phenotypic heterogeneity may partially explain the difficulty of confirming the exact role of this gene using both association and linkage methods. Four hundred one BPAD patients and 401 unrelated matched controls were recruited within a European collaborative project (BIOMED1 project in the area of brain research, European Community grant number CT 92-1217, project leader: J. Mendlewicz) involving 14 centers for a case-control association study with a tetranucleotide polymorphism in the TH gene. Patients and controls were carefully matched for geographical origin. Phenotypic heterogeneity was considered and subgroup analyses were performed with relevant variables: age at onset, family history, and diagnostic stability. No association was observed in the total sample or for subgroups according to age at onset (n = 172), family history alone (n = 159), or high degree of diagnostic stability and a positive family history (n = 131). The results of this association study do not confirm the possible implication of TH polymorphism in the susceptibility to BPAD.

Adult↗

European Collaborative Project on Affective Disorders: interactions between genetic and psychosocial vulnerability factors.

Despite strong evidence provided by genetic epidemiology of genetic involvement in the aetiology of bipolar and unipolar affective disorders, the exact nature of the predisposing gene(s) is still being investigated through linkage and association studies. The interaction of susceptibility genes and environmental factors in these diseases is also of fundamental importance and requires proper investigation. Interesting theories have recently been proposed examining the possible role of various chromosomal regions, candidate genes and mutations in affective disorders. Reliable multicentre-based methodology is currently being employed to examine these theories, with attention given to statistical analysis and the statistical power of the sample. The present article describes the European Collaborative Project on Affective Disorders (ECPAD) 'Interactions between genetic and psychosocial vulnerability factors', involving 15 European centres. A description is given of the association and family samples collected for the project and also the methodology used to analyse interactions in the gene-psychosocial environment. This material provides a powerful tool in the search for susceptibility genes in affective disorders and takes into account non-genetic aetiological factors.

Adolescent↗

Proteins of cytosol and amniotic fluid increase the voltage dependence of human type-1 porin.

Heat-stable proteins from human and porcine cytosol and human amniotic fluid were found to increase the voltage dependence of human type-1 porin reconstituted in planar phospholipid bilayers. Purification processes revealed that these regulatory molecules were characterized by anionic charge and apparent molecular weights of between 23 and 64 kDa. The human cytosol proteins exerted inhibitory activity only when added to the compartment with applied negative potential. The observed increase in voltage dependence of porin was due to the presence of specific proteins in cytosol and amniotic fluid, since human cerebral spinal fluid in comparable amounts had no significant effect on the channel properties. Furthermore, other anionic proteins and polypeptides investigated demonstrated no inhibitory activity, indicating that anionic charge alone could not mimic the molecular properties of the regulatory proteins. With respect to the well-documented expression of porin in the plasma membrane of various cells and species, the presented data give first clues for a biochemical regulation of the channel in this compartment.

Amniotic Fluid↗

The role of inflammatory cells and their proteases in extravascular fibrinolysis.

Extravascular fibrin formation and dissolution is a pivotal event in numerous inflammatory and malignant diseases. In inflammatory cells such as monocytes/macrophages, neutrophil granulocytes appear to interact intimately with hemostasis and regulate the activity of the cascade systems of coagulation and fibrinolysis. Proteases such as neutrophil elastase are thought to influence components of hemostasis, and furthermore provide an alternative pathway of fibrinolysis. Histological, experimental, and clinical data suggest that extravascular fibrinolysis, mediated both by the plasmin system and by proteases like neutrophil elastase, is a prominent finding in various diseases such as lung cancer, chronic inflammatory bowel disease, vasculitis and connective tissue disease, bacterial sepsis, and septic shock.

Endopeptidases↗

Channel active mammalian porin, purified from crude membrane fractions of human B lymphocytes or bovine skeletal muscle, reversibly binds the stilbene-disulfonate group of the chloride channel blocker DIDS.

Two new aspects of mammalian porin are presented. First, by affinity chromatography we show that channel active human or bovine porin reversibly bind the stilbene-disulfonate group of the chloride channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS). The procedure is suitable for further purification of porin after enrichment by ion exchange chromatography and shows a yield of 24.3%. The data support our recent proposal that VDAC forms part of the ORDIC channel complex which is affected in cystic fibrosis. Second, a purification scheme for mammalian porin is given starting with direct solubilisation of ground bovine skeletal muscle to avoid breaking up tissue. About 130 mg of channel active "Porin 31BM" are enriched from 946 g muscle tissue. Concerning its apparent molecular mass, primary structure, channel activity, channel conductance and voltage dependence the molecule shows high similarity to human porin. "Porin 31BM" is furthermore labelled by antibodies raised against human B lymphocyte derived "Porin 31HL".

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Comparison of low molecular weight heparins and unfractionated heparin after successive subcutaneous administration. A randomized controlled study in healthy volunteers.

The biological response to 4 different heparins after successive subcutaneous administration once daily for 5 days at a dose used for primary prophylaxis of deep vein thrombosis was investigated in a randomized cross-over study in 12 volunteers. Three different preparations of low molecular weight heparins (LMWH) were administered, 10,000 U unfractionated heparin (UFH) was used as a control. The anticoagulant properties in terms of anti-Xa activities, as measured by a chromogenic substrate assay or Heptest, showed high interindividual variations with peak levels 2 to 4 h following injections. There was a significantly higher increase of anti-Xa activities 3 h after administration at day 5, when compared with day 1, for two LMWH's, suggesting an accumulation of the anticoagulatory effect. The anticoagulant activity, especially when measured by Heptest, was significantly influenced by the body weight. This could be observed for all LMWH's. For the assessment of anticoagulant activity in LMWH-treated individuals, the chromogenic substrate assay and Heptest revealed maximal correlation (r = 0.51), while in UFH-treated individuals, peak correlation (r = 0.75) was observed between the partial thromboplastin time and thrombin clotting time. The chromogenic substrate method was the most sensitive anti-Xa assay, showing also the smallest interindividual variation. No significant influence of heparins neither on platelet count and function nor on fibrinolysis were recognized. Enhanced lipolytic activities were not observed. There was an increase of alanine aminotransferases induced by UFH as well as LMWH's, which, however, was most pronounced after UFH.

Adult↗

Half-life of single-chain urokinase-type plasminogen activator (scu-PA) and two-chain urokinase-type plasminogen activator (tcu-PA) in patients with acute myocardial infarction.

The pharmacokinetics of urokinase (two-chain urokinase-type plasminogen activator, tcu-PA) and single-chain urokinase-type plasminogen activator (scu-PA) were studied in 20 patients with acute myocardial infarction (AMI). Ten consecutive patients received 2.5 million units tcu-PA by bolus injection within 5 min during the first 6 h after AMI (group I). Ten further consecutive patients received 250,000 U tcu-PA within 5 min, followed by 4.5 million U scu-PA by intravenous infusion over 40 min (group II). An enzyme immunoassay was developed for urokinase antigen determinations, and a fibrin plate assay for determinations of fibrinolytic activity was applied. Using a 3-compartment model, in group I 98% of urokinase antigen were cleared with a half-life of 60.8 min. After scu-PA, urokinase antigen was cleared with half-lives (area under the curve in parentheses) of 6.9 min (74.8%), 26.5 min (23.6%), and 329.7 min (2.2%). The half-disappearance times of fibrinolytic activity were 18 and 8 min in group I and II, respectively. A more pronounced decrease of plasminogen was observed after tcu-PA.

Half-Life↗

Hirudin--a potential stabilizing factor for platelet preservation in transfusion.

The influence of additional hirudin in low doses on platelet and coagulation parameters was studied in platelet concentrates (PC) prepared by cytapheresis using citrate-dextrose solution formula A. The in vitro release of platelet factor 4 and beta-thromboglobulin was markedly lowered and morphological platelet alterations, as assessed by platelet size studies were considerably less accentuated in the presence of hirudin over a 5-day storage period; this suggests a possibly protecting effect on platelet function. No clear activation of the coagulation and fibrinolysis system was evident during PC storage with and without hirudin since thrombin-antithrombin III complexes and D-dimers did not markedly change.

Blood Coagulation↗