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Biomedical subjects

H Thoma

Publications and source records attributed to H Thoma.

At least 19 recordsLinked to original sources

The combined dexamethasone-CRH test before and after repetitive transcranial magnetic stimulation (rTMS) in major depression.

BACKGROUND: Hypothalamic-pituitary-adrenocortical (HPA) dysregulation assessed by the combined dexamethasone corticotropin releasing hormone test (DEX/CRH test) has been demonstrated to normalize after successful antidepressant pharmacotherapy. Here, we investigated whether repetitive transcranial magnetic stimulation (rTMS) also leads to a normalization of HPA system activity in depressed patients. METHODS: Thirty-seven medication free patients suffering from a major depressive episode (DSM-IV) underwent a DEX/CRH test before and after 13 daily sessions of left prefrontal rTMS in an open trial. RESULTS: There was an overshoot of CRH-induced cortisol release that was not affected by rTMS treatment. Postdexamethasone cortisol levels prior to CRH challenge decreased in responders after rTMS treatment, whereas no change of CRH-induced adrenocorticotropic hormone (ACTH) and cortisol release in responders or nonresponders was observed. CONCLUSIONS: The persisting HPA system hyperactivity after rTMS suggests a high risk for relapse and therefore argues for an immediate maintenance therapy in patients responding to this treatment.

Adult↗

Computerized generation of circadian sensor modal days with continuous glucose monitoring for comparison of various insulin regimens based on insulin glargine in type 1 diabetes.

AIM: Our aims were (1) to design and standardize a statistical approach for data reduction in continuous glucose monitoring, allowing comparison of circadian glycemic patterns in therapeutic subcohorts of patients with type 1 diabetes, and (2) to investigate the applicability of this approach for CGMS assessment in clinical study of basal insulin replacement quality with various timings of basal injections (pre-breakfast, dinner, bedtime) of a new insulin analog. METHODS: Prospective randomized three-arm parallel study with switch over after 6 months for another 3 months of free choice injection time point (options pre-breakfast, pre-dinner and bedtime) of the new insulin analog in 16 type 1 diabetic subjects on functional insulin treatment (FIT: basal, prandial and correctional dosages). CGMS was used at the end of each follow up period of a clinical study. Representative daily profiles were off-line computed as "circadian sensor modal days" for each insulin regimen consisting of consecutive means of hourly glucose values. RESULTS: Although the overall quality of glycemic control (HbAIC) for different regimens did not reach statistical differences, CGMS displayed slightly divergent maximal swings in the course of glycemia (p=0.04-0.08) and allowed--with delineated data reduction procedure--a reliable between treatment comparison. CONCLUSION: Off-line computation of "hourly circadian sensor modal days" for data reduction can be effectively used with CGMS for description of circadian glycemic patterns in type 1 diabetes.

Adult↗

Internal exposure to polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs) of Bavarian chimney sweeps.

This study was carried out to evaluate the internal exposure to polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs) of chimney sweeps in Bavaria compared to a control group without occupational exposure. The PCDD/PCDF concentrations in the blood fat of 227 chimney sweeps were compared with the concentrations in samples from 60 controls. Using an internal standard containing 17 (13)C(12)-labeled PCDD/F congeners, the samples were cleaned up after fat elution using standard methods. The statistical analysis was adjusted to account for demographic differences, dietary habits, smoking status, and both occupational and nonoccupational contact with chlorinated hydrocarbons. Detailed information on the type of heating in the households swept, the length of time the chimney sweeps had carried out the profession (min 34, med 195, max 466 months) and the protective measures employed, were used to examine the influence of the working conditions specific to chimney sweeps on the internal PCDD/PCDF exposure. The correlation between blood-fat PCB concentrations as well as urinary chlorophenol concentrations and the exposure to PCDDs/PCDFs was evaluated. The sum of PCDD/PCDF components in chimney sweeps, expressed by International Toxic Equivalents (I-TEQ), was significantly increased compared to the control group (median: 26.36 versus 20.75 pg I-TEQ/g blood fat). For 37 chimney sweeps (16.3%) the sum of PCDDs/PCDFs exceeded the 95th percentile of the control group, i.e., 38.23 pg I-TEQ/g blood fat. Multiple regression analysis revealed that in addition to occupation, the variables age, district, and proximity to a waste incineration plant seem to have an effect on the internal PCDD/PCDF exposure. An additional influence on the internal exposure could not be determined for any of the special aspects of the work. We identified no high correlations between the concentrations of PCBs and chlorophenols and PCDDs/PCDFs. This study revealed significantly higher internal exposure to PCDDs/PCDFs in chimney sweeps than in the control group. The differences are small and within the range of the internal exposure to PCDDs/PCDFs in blood found in the general population in Germany since 1989. Further investigations in to PCDD/PCDF-related diseases in these study groups were not carried out.

Adult↗

Functional and biological test of a 20 channel implantable stimulator in sheep in view of functional electrical stimulation walking for spinal cord injured persons.

A newly developed implantable stimulator with 20 output channels, mainly intended for the stimulation of lower extremities in paraplegics, was implanted in 6 sheep over a time period of 26 weeks. Five epineural electrodes each were used to contact various nerves at different locations to elicit hip and knee extension and flexion and to make carrousel and selective stimulation possible. Different electrode application strategies in view of paraplegic standing and walking were investigated. Additional implanted electrodes allowed M-wave monitoring for selectivity investigations in 3 sheep. Stimulator, electrode leads, and electrodes proved to be reliable. Selective stimulation with electrodes placed on the trunk of the sciatic nerve could be demonstrated but with bad reproducibility. Histological investigation of the tissues surrounding electrodes and leads showed the expected stable foreign body response. Strong hip and knee extension could be gained in all cases while only weak flexion forces could be elicited in most cases. Muscle biopsies showed that daily stimulation for 8 h at threshold level caused an increase in muscle Type I fibers and a decrease in Type IIc fibers. Implants and electrodes fulfill the most important functional and biological criteria for their clinical application for paraplegic walking. The intention to provide selective flexion functions via epineural stimulation could not be demonstrated sufficiently in this animal model.

Animals↗

Application of a purge and trap TDS-GC/MS procedure for the determination of emissions from flame retarded polymers.

Emissions of volatile organic compounds (VOCs) from different thermoplastic polymers used in electrotechnical applications were investigated using a purge and trap procedure that involved adsorption on Tenax GR. Results were compared to those for an operating TV set monitored in a test chamber. The analyses were in both cases carried out using thermodesorption gas chromatography with mass spectrometric detection (TDS-GC/MS). Substances identified were monomers, volatile additives, or related compounds. Special attention was given to the detection of halogenated compounds. Their origin was studied using reference samples and synthetic standards.

Air Pollutants↗

Effects of the metal type and the roughness of the die wall on the expended work for tablet ejection.

The aim of the present work was to obtain an impression about the consequences for the tableting process when dies of different quality are used. Two hard metal dies and one die made from tool steel, each with a distinct roughness of the die wall, were compared by compacting dry-blended powder mixtures on an eccentric tablet press. The feasibility of the tableting process was assessed by quantifying the ejection force and the work expended by the lower punch during a first phase of the ejection process. With decreasing amounts of lubricant, abrupt permanent impacts were observed leading to conditions at which an ejection was no longer possible. This observation did not depend on the roughness of the die wall used or on the compaction pressure, but strongly depended on the metal type of the die used and on the tested formulation. For the tool steel no difference was found in this respect between the two tested formulations (0.5% versus 2% silica aerogel). In either case, a concentration of 0.3% magnesium stearate was sufficient; however, a concentration of 0.2% magnesium stearate was not sufficient. For both hard metal dies, concentrations of 0.3% (0.5% silica aerogel) and 0.5% magnesium stearate (2% silica aerogel) were definitely not sufficient. Within the ranges above a minimum lubrication, the ejection force and the ejection work increased with the degree of the die wall roughness on a scale comparable to that of the tested formulation factors. In particular, if changes of the die tooling are likely to occur in the life cycle of a product, it is highly recommended that the quality of the dies be considered in the development phase.

Chemistry, Pharmaceutical↗

Psychopathological changes preceding motor symptoms in Huntington's disease: a report on four cases.

Neurodegenerative disorders often exhibit "classical" psychiatric symptoms as an initial presentation of the disease. Here we present four patients with different psychopathological abnormalities who were later diagnosed as having Huntington's disease. The range of symptoms covered affective and psychotic symptoms, antisocial behavior, cognitive problems reminiscent of dementia and suicidal idealisation. The pattern of progress of neuronal degeneration may be helpful in explaining the antecedent manifestation of psychiatric symptoms.

Adult↗

Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS.

In previous studies, fast repetitive transcranial magnetic stimulation (rTMS) with a frequency > 1 Hz demonstrated substantial antidepressant effects compared to sham rTMS. However, it is not clear whether fast rTMS is superior to slow rTMS (frequency < or = 1 Hz) which is safe at therapeutically promising higher intensities. The aim of this double-blind study was to compare the action of fast, slow and sham rTMS. Eighteen patients with pharmacotherapy-resistant major depression were randomized to receive fast (10 Hz), slow (0.3 Hz) or sham rTMS with 250 stimuli/day for 5 successive days. rTMS was applied at 90% motor threshold intensity to the left dorsolateral prefrontal cortex. Scores on the Hamilton Depression Rating Scale (HDRS), but not on the Montgomery-Asberg Depression Rating Scale (MADRS), showed a statistically significant time x group interaction with a reduction of 19% after slow rTMS. However, the effect was clinically marginal and not reflected by self-rating scores. Verbal memory and reaction performance were not impaired after rTMS, and there was even a statistically significant time x group interaction with improvement of verbal memory performance after fast rTMS. In conclusion, this study further supported the safety of rTMS but does not show any clinically meaningful antidepressant efficacy of rTMS at 250 daily stimuli over 5 days in pharmacotherapy-refractory major depression.

Adult↗

Establishment of a simple cleanup procedure and bioassay for determining 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalents of environmental samples.

The study was aimed at establishing a bioassay for the determination of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalents (TEQs) in environmental samples. Specifically, development of a rapid cleanup procedure adapted to the needs of the bioassay and simplification of the measurement of its endpoint, the induction of 7-ethoxyresorufin O-deethylase (EROD) in rat H4IIEC3/T hepatoma cells, were desired. The results indicate that a single "sandwich" column suffices to remove substances that may interfere with the bioassay from extracts of various environmental matrices such as sewage sludge, compost, soil, sediment, fly ash, tissue filter dust, and fire residue. The cumbersome conventional in vitro assay for EROD activity on cells exposed to the test material in culture plates could readily be replaced by a simple assay on intact cells grown and treated in 96-well microtiter plates. TEQ values obtained from the bioassays were consistently higher than those derived from chemical analysis of dibenzo-p-dioxins/furans and biphenyls by a factor of 1.5-3.0 depending on the matrix used. The results indicate that this bioassay, which combines a simple cleanup and a rapid procedure for measuring biological effects, offers a cost- and time-effective alternative to chemical analysis when screening large numbers of samples from complex environmental matrices.

Animals↗

[Present status and future aspects of the respiratory pacemaker].

Under certain conditions, phrenic pacing is a rare but most effective and attractive alternative for long-term ventilation. General indications concern diseases of the breathing center, for example Undine's disease (loss of CO2 sensitivity) in infants and high cervical spinal cord lesions in the level of C0 to C3. Despite of the advantage of physiologic respiration mode (no positive air pressure) compared to long-term ventilation, the phrenic pacemaker enables high life quality for the patients due to possibilities of closing of tracheostoma (Vienna system), an optimum in mobility and high cost effectiveness. International research and development in this area concerns 1. nerve transposition of an innervated nerve to a denervating phrenic nerve, 2. additional stimulation of thoracal muscles for inspiration, 3. additional stimulation of expiration, 4. endoscopic operative positioning of the electrodes, 5. development of a pacer with sensor input for an individual respiration rhythm (controlled by the vocal cord) and 6. development of a fully implantable system Improvements of the present pacemaker system may lead to enlargement of indications, for example use in patients with severe nocturnal arrhythmias in respiration.

Adult↗

Useful applications and limits of battery powered implants in functional electrical stimulations.

Battery powered stimulation implants have been well-known for a long time as heart pacemakers. In the last few years, fully implantable stimulators have been used in the field of functional electrical stimulation (FES) for applications like dynamic cardiomyoplasty and electro-stimulated graciloplasty for fecal incontinence. The error rate of battery powered implants is significantly smaller than that for conventional stimulator systems, and the quality of life for the patients is increased because the need for an external power and control unit is eliminated. The use of battery powered implants is limited by the complexity of the stimulation control strategies and the battery capacity. Therefore, applications like the stimulation of lower extremities for walking, cochlea stimulation, or direct muscle stimulation cannot be supported. The improvement of implantable batteries, microcontrollers, and ultralow power products is ongoing. In the future, battery powered implants will also meet the requirements of complex applications. Systems for restoration of hand and breathing functions after spinal cord injury can be the next field of use for battery powered implants. For these purposes, we developed a battery powered multichannel implant with a sufficient life span for phrenic pacing. The problems during development and the limits of this system are described in this paper.

Cardiomyoplasty↗

Computer aided adjustment of the phrenic pacemaker: automatic functions, documentation, and quality control.

Electrical stimulation of the phrenic nerves of patients with complete ventilatory insufficiency with the Vienna respiratory pacemaker has been in clinical use since 1983. During the adjustment of stimulation parameters with this device, the following problems have occurred: for some measurements like the recruitment curve, series of complete inspiration cycles have to be stimulated, which causes the danger of muscle fatigue for unconditioned patients. The documentation is completed predominantly by hand, taking time and increasing the possibility of error. As a first step to solve these problems, we developed a new stimulation and measurement system. It consists of a PC with data acquisition hardware, the necessary sensors, and amplifier circuitry. The implanted stimulator is controlled via the parallel interface. The new system offers some advantages: computer control shortens the time for measurement and documentation, and the stress on the patient and the risk of error is reduced; synchronized measurement makes it possible to use single stimulation pulses instead of bursts and ramps to reduce diaphragm fatigue; digital signal processing improves measurement results and reproducibility; and help functions and self tests are provided, together with a graphical user interface. We used sensors for air flow, diaphragm EMG, and acceleration, on up to 8 channels simultaneously. Combined sample rates of up to 100 kS/s were possible. The system could be adapted for other uses involving functional electrical stimulation with our implantable nerve stimulators. Using this equipment saves a lot of effort, and the adjustment process can be focused on improved stimulation results and better performance for the patient. Current research is studying implementation of automatic functions like acquisition of stimulation thresholds. This could result in a predominantly automated adjustment of the phrenic pacemaker and even in a closed-loop controlled system in the future.

Computer Simulation↗

Monitoring set-up for selection of parameters for detection of hypoglycaemia in diabetic patients.

Recurrent severe hypoglycaemia is often an unsolved problem in diabetic patients under intensified insulin treatment. As no reliable long-term stable blood glucose sensor has yet been developed, registration of other body function changes could help to detect severe hypoglycaemia. A measuring system is described, capable on the one hand of recording EEG, heart rate, peripheral pulse, skin temperature, respiratory movements, skin impedance and arterial blood pressure, and capable of registering plasma glucose, counter-regulatory hormones, symptoms and cognitive performance under experimental conditions during hypoglycaemia, on the other. In a clinical study involving both insulin-induced hypoglycaemia in healthy subjects and insulin-dependent diabetic patients, the practical value and the character of changes of the recorded parameters are investigated. Currently insensitivity to hypoglycaemia, impracticability, complexity or susceptibility to artefacts make use of most parameters unsuitable for hypoglycaemia prevention. It is believed, however, that future efforts could result in indirect registration of hypoglycaemia, including a qualified combination of different parameters, individual adaptation in accordance with particular responses of individual patients, together with new measuring and sensor techniques.

Adult↗

[Does long-term hospitalization modify cardiovascular morbidity in schizophrenic patients?].

Cardiovascular risk factors, electrocardiographic findings and preexisting diseases of the cardiovascular system were recorded in 90 schizophrenic patients (mean age 62.6 yrs., mean duration of hospitalisation 28.6 yrs.). The obtained data were compared with a group of depressive inpatients matched for age and sex and with corresponding data of the german population. Although among the schizophrenic patients heavy cigarette-smoking was significantly more frequent, hints for a myocardial infarction in history were found in only 3 of these patients and, in contrast, in 7 depressive patients. Systolic and diastolic blood pressure did not differ among depressive and schizophrenic subjects with mean levels in both groups being lower than in the corresponding age of the general population. Total cholesterol levels were lowest in the schizophrenics; in the depressive patients, however, lower than in the general population. There was a continual increase of cholesterol with progressive age in depressive subjects and in the general population. An adverse tendency was found in the long-term-hospitalized schizophrenics of both genders. In male schizophrenics a significant negative correlation between the duration of hospitalisation and both serum cholesterol and diastolic blood pressure could be observed. This may explain cardiovascular mortality rates in these patients which are not elevated in spite of heavy smoking and lack of movement.

Adult↗

Vienna phrenic pacemaker--experience with diaphragm pacing in children.

Eight children, five boys and three girls, aging from 2 to 13 years (M = 9 +/- 3) were treated with the "Vienna phrenic pacemaker". Indication for implantation was central alveolar hypoventilation syndrome (CAH) in one case and total ventilatory insufficiency due to high cervical cord or brain stem lesion (SCI) in seven cases. Four electrodes were applied to each phrenic nerve via sternotomy. Both hemidiaphragms were paced synchronously with increasing duty cycles to condition the diaphragms for continuous electrophrenic respiration (EPR). EPR could be performed successfully in all children but one. Four children could achieve chronical EPR, one is in conditioning period. Two patients could not be discharged from hospital due to parental neglect and died after two and three years of intermittent stimulation. Six children could be discharged from hospital, two of them died after one and four years of chronic pacing. In one case tracheotomy could be closed definitively. Ventilatory insufficiency due to CAH and SCI can be treated even in children with diaphragm pacing, provided the indication for implantation, containing medical and social aspects, was made correctly. Diaphragm pacing probably will not lengthen life of severely injured children but it can increase the quality of their life and therefore should be preferred to positive pressure mechanical ventilation.

Adolescent↗

EEG topography during insulin-induced hypoglycemia in patients with insulin-dependent diabetes mellitus.

A group of young patients with insulin-dependent diabetes mellitus (n = 14; 8 men, 6 women; 33.1 +/- 8.9 years) were examined by topographic EEG mapping under normoglycemic and hypoglycemic conditions (glucose levels after intravenous insulin injection down to 32.6 +/- 7.6 mg/dl). From the clinical aspect, 7 of them had a good and 7 had a poor awareness of hypoglycemia. During hypoglycemia, a decrease in alpha activity (p < 0.05), an increase in delta (p < 0.05), and especially in theta activity (p < 0.05) were found. The most sensitive parameter was the alpha/theta ratio. In the range of slight hypoglycemia (50-60 mg/dl) the increase in delta and theta activity showed a topographic maximum in lateral frontal regions. During deep hypoglycemia there was a topographic maximum of slow frequencies in posterior parts of the brain (centrotemporal to parieto-occipital regions). The differences between the group with good and with poor awareness of hypoglycemia were most pronounced during slight hypoglycemia in C3, C4, and Pz (p < 0.05). At lower glucose levels group distinction was no longer possible. These EEG changes correspond to a temporary organic brain syndrome.

Adult↗