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Biomedical subjects

M Voss

Publications and source records attributed to M Voss.

At least 19 recordsLinked to original sources

Cortical correlates of TMS-induced phantom hand movements revealed with concurrent TMS-fMRI.

We studied an amputee patient who experiences a conscious sense of movement (SoM) in her phantom hand, without significant activity in remaining muscles, when transcranial magnetic stimulation (TMS) is applied at appropriate intensity over the corresponding sector of contralateral motor cortex. We used the novel methodological combination of TMS during fMRI to reveal the neural correlates of her phantom SoM. A critical contrast concerned trials at intermediate TMS intensities: low enough not to produce overt activity in remaining muscles; but high enough to produce a phantom SoM on approximately half such trials. Comparing trials with versus without a phantom SoM reported phenomenally, for the same intermediate TMS intensities, factored out any non-specific TMS effects on brain activity to reveal neural correlates of the phantom SoM itself. Areas activated included primary motor cortex, dorsal premotor cortex, anterior intraparietal sulcus, and caudal supplementary motor area, regions that are also involved in some hand movement illusions and motor imagery in normals. This adds support to proposals that a conscious sense of movement for the hand can be conveyed by activity within corresponding motor-related cortical structures.

Adult↗

Transcranial magnetic and electrical stimulation compared: does TES activate intracortical neuronal circuits?

OBJECTIVE: To determine whether, and under which conditions, transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) can activate similar neuronal structures of the human motor cortex, as indicated by electromyographic recordings. METHODS: Focal TMS was performed on three subjects inducing a postero-anterior directed current (p-a), TES with postero-anteriorly (p-a) and latero-medially (l-m) oriented electrodes. We analyzed the onset latencies and amplitudes (single-pulse) and intracortical inhibition and excitation (paired-pulse). RESULTS: TMS p-a and TES p-a produced muscle responses with the same onset latency, while TES l-m led to 1.4-1.9 ms shorter latencies. Paired-pulse TMS p-a and TES p-a induced inhibition at short inter-stimulus intervals (ISI) (maximum: 2-3 ms) and facilitation at longer ISIs (maximum: 10 ms). No inhibition but a strong facilitation was obtained from paired-pulse TES l-m (ISIs 1-5 ms). CONCLUSIONS: Our findings support the hypothesis, that current direction is the most relevant factor in determining the mode of activation for both TMS and TES: TMS p-a and TES p-a are likely to activate the corticospinal neurons indirectly. In contrast, TES l-m may preferentially activate the corticospinal fibres directly, distant of the neuronal body. SIGNIFICANCE: TES is a suitable tool to induce intracortical inhibition and excitation.

Adult↗

A cortico-cortical mechanism mediating object-driven grasp in humans.

Humans and other primates demonstrate an exquisite ability to precisely shape their hand when reaching out to grasp an object. Here we used a recently developed transcranial magnetic stimulation paradigm to examine how information about an object's geometric properties is transformed into specific motor programs. Pairs of transcranial magnetic stimulation pulses were delivered at precise intervals to detect changes in the excitability of cortico-cortical inputs to motor cortex when subjects prepared to grasp different objects. We show that at least 600 ms before movement, there is an enhancement in the excitability of these inputs to the corticospinal neurons projecting from motor cortex to the specific muscles that will be used for the grasp. These changes were object- and muscle-specific, and the degree of modulation in the inputs was correlated with the pattern of muscular activity used later by individual subjects to grasp the objects. In a number of control experiments, we demonstrated that no change in excitability was observed during object presentation alone, under conditions in which subjects imagined grasping the object, or before movements involving the same muscles but without an object. This finding demonstrates a cortico-cortical mechanism subserving the transformation from the geometrical properties of an object to the outputs from motor cortex before grasp that is specific for object-driven movements.

Adult↗

Pharmacogenomic assessment of treatment options in gestational diabetes.

Gene expression profiles offer a multidimensional view of metabolic diseases, typically characterized by a single parameter, and can provide a basis for choosing between therapies yielding a common clinical end point. We applied such an approach in gestational diabetes mellitus (GDM). Gene expression was examined in four maternal tissues and placentas from normal patients and euglycemic GDM patients, undergoing elective Cesarean sections at term, treated either by diet or diet plus insulin. Deviations from normal were 11-fold greater for the patients treated by diet, alone, than for patients treated by diet plus insulin. Assuming the achievement of a "normal" gene expression profile, in addition to euglycemia, is a desirable outcome of treatment, insulin treatment appears to have a beneficial effect in the treatment of GDM. Subsequently, we utilized the expression data to identify serum biomarkers that provide ways to monitor the benefits of insulin treatment in GDM.

Adipose Tissue↗

Myocardial cytokine gene expression is higher in aortic stenosis than in idiopathic dilated cardiomyopathy.

OBJECTIVE: To investigate cytokine gene expression in patients with aortic valve stenosis (AS) and with idiopathic dilated cardiomyopathy (DCM), and to correlate wall stress with myocardial proinflammatory cytokine gene expression. METHODS: Human left ventricular (LV) myocardial biopsies were obtained for subsequent reverse transcription polymerase chain reaction of tumour necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and IL-6 mRNA. The study population consisted of 24 patients with AS and 10 patients with idiopathic DCM. RESULTS: Patients with AS had a larger ejection fraction (56 (5) v 37 (4)%, p < 0.01), smaller LV end diastolic volumes (146 (11) v 267 (21) ml, p < 0.01), and lower end systolic wall stress (44 (7) v 112 (11) kdyn/cm2, p < 0.001). Upregulation of TNFalpha, IL-1beta, and IL-6 gene expression was detected in both groups. However, TNFalpha gene expression was significantly higher in AS than in DCM (p = 0.009). No correlation was found between haemodynamic parameters and TNFalpha gene expression. In patients with AS there was a strong inverse relation between circulating TNFalpha and TNFalpha gene expression (r = -0.685, p = 0.014), between circulating TNFalpha and IL-1beta gene expression (r = -0.664, p = 0.018), and between soluble TNF receptor 2 and TNFalpha gene expression (r = -0.685, p = 0.020). Myocardial gene expression of TNFalpha was significantly higher in patients with well compensated AS than in patients with decompensated AS (p = 0.017). Similarly, patients with decompensated DCM were characterised by significantly lower TNFalpha gene expression than were patients with well compensated DCM (p = 0.011). CONCLUSION: TNFalpha gene expression is significantly higher in patients with pressure overload than in normal hearts, in patients with idiopathic DCM, and in patients with compensated versus decompensated heart failure. Secondly, in patients with AS proinflammatory cytokine gene expression did not affect systolic performance. The higher TNFalpha gene expression in patients with compensated heart failure suggests that cytokine gene expression has an adaptive role in the early phase of LV remodelling.

Aged↗

[Chronic eosinophilic pneumonia].

HISTORY AND ADMISSION FINDINGS: A 43-year-old woman (patient 1) and a 58-year-old man (patient 2) presented with fever, nocturnal perspiration, dry cough, dyspnoea and general weakness. These symptoms had been present for several months. Repeated courses of antibiotic treatment as outpatients had failed. On admission their general condition was unremarkable. INVESTIGATIONS: The differential blood count revealed marked eosinophilia of 35% and 27%, respectively, and raised infection parameters. Results of laboratory tests were unremarkable. Conventional radiological films and CT of the thorax showed infiltrates, especially in the periphery. In both patients bronchoscopy revealed moderately severe bronchitis. Broncho-alveolar lavage and the peripheral blood count showed marked eosinophilia of 61% and 54%, respectively. Biopsies did not reveal necrosis, fungal infection, parasites, granulomas or vasculitis. DIAGNOSIS, TREATMENT AND COURSE: The described findings indicated a chronic eosinophilic pneumonia (CEP) in both patients. Treatment was initiated with high steroid dosage, namely 60 mg prednisolone equivalent daily, gradually reducing with improvement. The symptoms rapidly lessened and the radiological changes regressed after ca. 14 days. Intermittent recurrences were noted in both patients on reduction or termination, respectively, of the steroid treatment which had lasted for several months. CONCLUSIONS: CEP is an important disease to be considered in the differential diagnosis of unclear pulmonary infiltrates associated with an increased eosinophilia in both peripheral blood and the lungs. In some cases it may be necessary to continue steroid treatment over long periods, even years, to bring the pulmonary changes of CEP under control.

Adult↗

Thromboembolic disease and air travel in pregnancy: a survey of advice given by obstetricians.

The objective of this study was to document the awareness of risk and the nature of advice given by obstetricians to pregnant women who intend to travel by air and to compare the results with the advice given in an opinion paper of the Royal College of Obstetricians and Gynaecologists. The results were based on a self-completed questionnaire. All registered members of the Royal College of Obstetricians and Gynaecologists comprising 1349 individuals, obtained from a list provided by the RCOG, were invited to participate. An anonymous postal questionnaire was completed by the individuals before publication of the opinion paper of the RCOG. A total of 862 (62%) questionnaires returned, and 690 (51%) were available for analysis; 67% of obstetricians regard flying as being safe throughout pregnancy, 33% only in the 2nd and 3rd trimester. Nearly all obstetricians advised on simple prophylactic measures such as mobilisation, fluid intake and leg exercise. Fifty-three per cent would advise the use of prophylactic aspirin (75 mg), 49% the use of compression stockings; 4% recommended heparinisation; 44% believed this advice to be applicable only for the 2nd and 3rd trimester, while the RCOG emphasises that the risk of developing venous thromboembolism begins in the 1st trimester. Obstetricians as well as other health professionals need to be made aware that advice on air travel in pregnancy needs to start in the 1st trimester. Further research is needed to explore the relevance of the duration of flight when considering the application of thromboprophylactic measures as well as the value and choice of pharmacological treatment such as aspirin and heparin.

Aircraft↗

Lack of telomerase activity in human mesenchymal stem cells.

Telomerase activity and telomere maintenance have been associated with immortality in tumor and embryonic stem cells. Whereas most normal somatic cells are telomerase negative, low levels of this enzyme have been found in adult stem cells from the skin, gut and the hematopoietic system. Here, we show that telomerase activity is not detectable in human mesenchymal stem cells (hMSCs), which have the phenotype SH2+, SH3+, SH4+, CD29+, CD44+, CD14-, CD34- and CD45-, and have the capacity to differentiate into adipocytes, chondrocytes and osteoblasts. These data suggest that hMSCs have a different telomere biology compared to other adult stem cells. Alternatively, true mesenchymal stem cells might be a very rare subpopulation that have a detection level that is below the sensitivity of the TRAP assay.

Antigens, CD↗

Procalcitonin is a valuable prognostic marker in cardiac surgery but not specific for infection.

BACKGROUND: The prognostic value of elevated serum levels of procalcitonin (PCT) in patients early after cardiac surgery on cardiopulmonary bypass (CPB) remains unclear. In a prospective study, we investigated whether PCT is useful as a prognostic marker in cardiac surgery with respect to mortality, complications and infections, and whether PCT is a specific marker for occurrence of infections. METHODS: Within 8 months, a subset of 80 high-risk patients (APACHE II-score: 25.1 +/- 4.7 (mean +/- SD)) out of a consecutive cohort of 776 patients was investigated. Demographic data, operative data and clinical endpoints (mortality, infection, severe complication) were documented. Serum levels of PCT were analyzed preoperatively and at postoperative day 1. RESULTS: Hospital mortality in this high-risk group was 21.3 %, infections occurred in 33.8 % and complications in 58.8 % of the patients. Preoperative PCT was normal in all patients. Postoperative PCT was increased in non-survivors compared to survivors (34.3 +/- 7.0 ng/ml vs. 15.9 +/- 4.9 ng/ml; p < 0.05), in patients with severe complications (30.3 +/- 6.7 ng/ml vs. 5.5 +/- 1.4 ng/ml; p < 0.05) and in patients with infections (38.4 +/- 11.3 ng/ml vs. 10.8 +/- 1.6 ng/ml; p < 0.05). Area under receiver operating characteristic curve for PCT as predictor of mortality, infections and complications was 0.772 (95 %-confidence-interval (CI): 0.651 - 0.894), 0.720 (95 %-CI: 0.603 - 0.837) and 0.861 (95 %-CI: 0.779 - 0.943), respectively. PCT was not different with infectious compared to non-infectious complications. CONCLUSIONS: High levels of PCT are associated with mortality, infections, and severe complications early after cardiac surgery using cardiopulmonary bypass and therefore provide a valuable prognostic marker. However, PCT does not discriminate between infectious and non-infectious complications.

Aged↗

Autoantibodies in sera of pancreatic cancer patients identify recombination factor Rad51 as a tumour-associated antigen.

PURPOSE: The recombination factor Rad51 is highly expressed in human pancreatic adenocarcinoma. In this study we asked whether high-level expression of Rad51 antigen stimulates a B-cell response leading to Rad51-specific autoantibodies in human pancreatic cancer patients. METHODS: Sera of patients suffering from pancreatic cancer (57) as well as sera of healthy donors (86) were screened for Rad51 autoantibodies by Western-blot analysis. Rad51 over-expressing cell lines were used as antigen source. RESULTS: Four out of 57 (7%) sera tested were found positive for Rad51 autoantibodies of IgG subclass, while all 86 control sera were negative. CONCLUSION: This observation identifies Rad51 as a tumour-associated antigen in pancreatic adenocarcinoma. Since high-level expression of Rad51 is restricted to tumour cells, Rad51 is also a tumour-specific antigen. Further analyses should reveal whether Rad51 might also function as a tumour-specific transplantation antigen (TSTA) and whether it might serve as a target for new immunotherapeutical approaches.

Adenocarcinoma↗

Influence of photoperiod on the behavioral response to olfactory stimulation in the snail Helix pomatia L.

An ethanol vapor concentration of 1.6 mmol/l was used to test the diurnal variations of the olfactory response in two groups of snails, which were adapted to different light-dark cycles. The results revealed that the olfactory sensitivity to stimulation with ethanol was significantly increased during the day-time, which corresponds to the scotophase of the light-dark cycle, to which the animals had been adapted (chi2-test, P < 0.01).

Animals↗

Electrophysiological responses to thermal stimuli in peripheral nerves of the African giant snail, Archachatina marginata S.

In Archachatina marginata S. the activity of 264 single units of the lip nerves and the tentacle nerve was recorded during thermal stimulation of the lip region. 17.8% of all fibres responded with an increase in neuronal activity to temperature changes in the range from 12 to 36 degrees C. The amount of fibres responding to peripheral warm or cold stimuli varied between the investigated nerves. In the tentacle nerve (N. olfactorius) 30.5% of the neurons responded either to peripheral warming or cooling. In the three lip nerves N. labialis internus, N. labialis externus, and N. labialis medianus 20, 17, and 9.5%, respectively, proved to be thermoresponsive. Additional behavioural tests revealed that the thermopreferendum of Archachatina marginata S. is in the broad range between 13 and 32 degrees C.

Journal Article↗

High-performance liquid chromatography/fluorescence detection of S-methylglutathione formed by glutathione-S-transferase T1 in vitro.

Glutathione-S-transferase T1 (GSTT1-1) is a major isoenzyme for the biotransformation of halomethanes. The enzyme activity is located, among other places, in human liver and erythrocytes and is subject to a genetic polymorphism. Metabolism of the halomethanes via GSTT1-1 yields S-methylglutathione (MeSG). A new HPLC assay for the enzymatic formation of MeSG was developed. The glutathione conjugate was derivatized with 9-fluorenylmethyl chloroformate, followed by reverse-phase HPLC with gradient elution and fluorescence detection. The limit of detection was as low as about 39 pmol MeSG on-column. Including derivatization and HPLC analysis, samples could be run at 42-min intervals, thus enabling a high sample throughput. The entire method was validated for analyte recovery (78.2%) and for variations in detector response with replicated injections (11.8%) and with analyses on each of 11 consecutive days (15.2%) with erythrocyte lysate incubations as the matrix. The time-, protein-, and substrate-dependences of the enzymatic catalysis with the model substrates methyl bromide (MeBr) and methyl chloride (MeCl) were studied. Due to its strong electrophilic character, MeBr caused a high level of spontaneous MeSG formation from glutathione in a protein-free medium and a substrate-trapping side reaction in the presence of proteins. Therefore, enzymatic MeSG formation rates may only be determined with MeBr concentrations of at least 3000 ppm in the presence of limited amounts of protein (e.g. 100 microl erythrocyte lysate). In contrast, MeCl showed a lower alkylating potential allowing enzymatic catalysis to be the dominant reaction in incubations with 10,000 ppm MeCl and 2 ml erythrocyte lysate.

Chromatography, High Pressure Liquid↗

Diagnostic dilemmas in abdominal tuberculosis in children.

The authors review 45 pediatric patients with intra-abdominal tuberculosis (ATB) treated between May 1990 and April 1998. The diagnosis was confirmed histologically or by positive culture for Mycobacterium tuberculosis. Clinical presentation was with an abdominal mass (12), subacute obstruction (11), ascites (5), mass and ascites (4), peritonitis (4), and 9 unusual presentations. Mantoux tests were positive in 68% of patients tested. There were radiologic features suggestive of pulmonary TB in 29 patients (64%); abnormal abdominal radiographs were recorded in 21 (47%). Lymphadenopathy was noted on abdominal ultrasound in 23 of 30 patients (77%) and on computed tomography scan in a further 3 of 8 patients investigated. Ascitic fluid adenosine deaminase (ADA) levels were greater than 30 IU/l in 3 of 4 patients (75%), suggesting ATB. All 28 patients screened for human immunodeficiency virus were negative. A surgical procedure was performed in 39 patients. 29 (74%) had an elective diagnostic laparotomy for tissue diagnosis. One (3.4%) developed a postoperative intra-abdominal abscess. Ten (26%) presented with complications requiring surgical intervention including perforated viscus, segmental bowel resection, strictureplasty, adhesiolysis, or ileostomy. One of the latter died due to sepsis after having complications of persistent intestinal obstruction and cecal perforation. The authors recommend an aggressive approach to patients with suspected ATB in order to obtain an early definitive diagnosis, prevent complications, and reduce morbidity and mortality. They emphasize the importance of tissue diagnosis and confirmation by culture.

Abdominal Abscess↗

[Risk assessment of mitral valve surgery combined with myocardial revascularization].

INTRODUCTION AND OBJECTIVES: Patients with combined mitral valve operation and coronary artery surgery represent a high risk group. The aim of this retrospective study was to evaluate which factors affect early and late postoperative results in this particular group of considered high risk patients. PATIENTS AND METHOD. Between 1984 and 1997, 264 patients (mean age: 63 +/- 7.3 years) underwent mitral valve surgery (199 patients; 75% mitral valve replacement, 25% mitral valve repair) in combination with coronary revascularization (mean 2.4 +/- 1.3 grafts). Follow-up comprised a mean of 69 +/- 42 months and was 98.3% complete. RESULTS: Early mortality was 10.6% (28/264). Ischemic mitral regurgitation operated on in emergent status, moderate to severe reduced left ventricular function and advanced age (> 60 years) were independently associated with early hospital mortality (p < 0.05). Ischemic etiology of mitral valve disease (emergency and elective operations), severity of mitral regurgitation and New York Heart Association (NYHA) functional class IV were related to early hospital mortality, only with univariate statistics. Actuarial survival was 86, 69 and 48% at 1, 5 and 10 years, respectively. The preoperative NYHA functional class was the only variable independently related to late survival. Eighty-five percent of the surviving patients were in NYHA functional class I and II. CONCLUSIONS: Mitral valve operation combined with coronary artery bypass grafting is associated with a high early hospital mortality. Independent risk factors of early mortality are emergency operation of ischemic mitral valve disease, reduced left ventricular function and advanced age. Long term survival is independently influenced only by preoperative NYHA functional class IV.

Adult↗

The dependence of thermopreferendum in Helix pomatia L. on air temperature.

Behavioural tests with 192 specimen of the roman garden snail Helix pomatia L. were performed in order to clarify whether the thermopreferendum of this pulmonate is influenced not only by the temperature of the substratum but also by air temperature. For this purpose, the snails were exposed to a horizontal temperature gradient of the substratum at different air temperatures between 10 and 30 degrees C. The results show that the selection of substratum temperature depends on the air temperature: the lower the air temperature, the lower is the temperature of the substratum preferred by the snails. Obviously, the animals tend to keep the difference between air temperature and temperature of the substratum as small as possible. This behaviour might be a mechanism to reduce the temperature gradient in the snail's body and to adjust the metabolic rate to cardiac output.

Journal Article↗

Combined mitral valve and coronary artery surgery: ischemic versus non-ischemic mitral valve disease.

OBJECTIVES: Mitral valve combined with coronary artery surgery is associated with a higher hospital mortality than each operation in particular. Controversy exists regarding the predictive value of ischemic mitral valve disease (MVD) on outcome. METHODS: Between 1984 and 1997, 262 patients underwent mitral valve operations (replacement, n = 198; repair, n = 64) in combination with coronary revascularization. The etiology of MVD was secondary to ischemic heart disease (group I) in 82 (31%) patients, and non-ischemic (group II) in 180 (69%) patients (rheumatic, 139 patients (53%); degenerative, 41 patients (16%)). Both groups were similar in age, cardiac risk factors and pulmonary artery pressure. Patients of group I had significantly more severe coronary artery disease, more often an impaired left ventricle and myocardial infarction, and were in a worse functional condition. The mean number of bypass grafts was significantly higher in group I. The follow-up was 98% (230/234 patients). RESULTS: With 19.5%, the hospital mortality was significantly increased in group I compared with 6.7% in group II (P = 0.002; overall, 10.7%). Mitral valve repair or replacement had no influence on early outcome, although mitral valve repair was performed more often in group I (37 versus 19%). The survival (valve-related event-free survival) after discharge from hospital in the 1st, 5th and 10th year was 94 (94%), 70 (66%) and 53% (35%) in group I and 96 (95%), 79 (76%) and 54% (41%) in group II, respectively. The long-term functional capacity was equally good in both groups (New York Heart Association mean, 1.86 versus 1.72). CONCLUSIONS: Patients with ischemic MVD are in a worse cardiac condition with significantly higher hospital mortality than patients with non-ischemic MVD and coronary artery bypass grafting. Once discharged from hospital, both groups have comparable long-term outcomes, with the best results in patients with degenerative MVD.

Aged↗

Virulence-associated genes in avian pathogenic Escherichia coli (APEC) isolated from internal organs of poultry having died from colibacillosis.

Escherichia coli infections are responsible for significant losses in the poultry industry in many parts of the world. The pathogenesis and the role of virulence factors are not yet totally elucidated. We, therefore, examined 150 E. coli strains isolated from visceral organs of poultry having died from colibacillosis for the presence of virulence-associated genes by PCR. The E. coli strains were investigated for the presence of a total of 17 virulence-associated genes described for diarrheagenic (stx1/2, eae, hlyEHEC, estl, eltI, astA, cdtb), septicemic (hlyA, papC, cnf1/2, fyuA, irp2) and avian pathogenic E. coli (APEC; iucD, tsh, fimC, and hlyE as well as stx2f). Seven genes were significantly distributed among APEC strains, while most of the other investigated genes could be demonstrated only sporadically or not at all. FimC (Type I fimbriae) was detected with the highest prevalence in 92.7% of the isolates. Most of the strains harboring iucD (88.7%) also gave positive results for tsh (85.3%). Genes fyuA (ferric yersiniabactin uptake) (66.0%) and irp2 (iron-repressible protein) (68.0%), necessary for Yersinia to acquire iron in the mouse infection model, were regularly detected in combination. Moreover, we found papC (pyelonephritis-associated pili) in 30.0% and astA (enteroaggregative heat stable toxin) in 17.3% of the field strains. A significant amount of strains (57.3%) harbored a combination of iucD, tsh, fimC, fyuA and irp2 virulence-associated genes, presumably rendering these strains particularly virulent. These findings provide novel insights into the presence and distribution of virulence-associated genes in avian pathogenic E. coli field strains, which will help to more comprehensively characterize APEC in future epidemiological studies. It is assumed that the existence of two iron acquisition systems points towards their important role in virulence. Furthermore, we suggest that characterization of the respective phenotypes in infection models will provide substantial information to better understand the pathogenesis of colibacillosis in poultry.

Animals↗