Biomedical subjects
Publications and source records attributed to R Huber.
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OBJECTIVE: To identify factors, predicting which patients of a large German university hospital request for a consultation on complementary and alternative medicine (CAM). PATIENTS AND METHODS: 350 patients of 3 medical and a psychosomatic department of the University Hospital Freiburg were consecutively surveyed with respect to their coping strategies, health locus of control, anxiety, depression, and the request for a consultation on CAM. Predicting factors were identified via logistic regression models. RESULTS: The request for a CAM consultation was primarily determined by an active coping strategy (odds ratio 1.66, 95% confidence interval 1.27-2.17, p = 0.0002) and a low Karnofsky index (odds ratio 0.79, 95% confidence interval 0.62-0.99, p = 0.0417). Anxiety, depression or internal health locus of control correlated with each other but could not be proved as independent factors for the request for a CAM consultation. CONCLUSION: Patients of a university hospital with an active disease coping have a need for information about CAM.
BACKGROUND: Two examples of clinical research with mistletoe extracts were used to demonstrate essential difficulties in carrying out randomized and placebo-controlled trials. STUDY 1: In a randomized, placebo-controlled, double-blind study investigating the immunological effects of mistletoe extract, healthy subjects were asked to state whether, in their estimation, they had been treated with verum or a placebo. Due to the intrinsic effects of the mistletoe therapy--local inflammatory reactions at the injection site--100% of the subjects treated with verum and 77% of those treated with a placebo made a correct assessment of their therapy. Although double-blind trials are preferable from the methodological point of view--above all in QoL research--this study shows that double blinding is barely achievable when the investigated therapy has obvious (side) effects. STUDY 2: A prospective, randomized, multicenter study of a mistletoe therapy complementary to chemotherapy treatment of breast cancer had to be stopped after a period of 28 months, because it proved impossible to recruit more than 16 patients in six large study centers. With regard to this example and to other failed, GCP-compliant clinical trials on mistletoe therapy we describe which factors interfere with successful clinical trials. One important point, especially in the investigation of complementary cancer treatments, is that cancer patients are unwilling to have their treatment determined by randomization. Many cancer patients in Germany have their own point of view, as to whether a complementary treatment could be of benefit to them or not. Faced with a life-threatening disease they wish to determine this part of their treatment themselves. CONCLUSION: This background elucidates the need for improving the methodology of non-randomized trials to obtain objective and reliable results even in these fields of clinical research.
We demonstrate a novel compact femtosecond Ti:sapphire laser system operating at repetition rates from 10 kHz to 4 MHz. The scheme is based on the combination of a broadband cavity-dumped oscillator and a double-pass Ti:sapphire amplifier pumped by a low-noise cw solid-state laser. Amplified pulses with an extremely smooth spectrum, a duration of only 12 fs, and less than 0.25% rms fluctuation are generated in a beam with M2 < 1.2. A maximum pulse energy of 210 nJ and an average output power of as much as 720 mW are achieved. This output energy is sufficient to generate a stable continuum in a sapphire disk.
The transverse polarization of electrons emitted in the beta decay of polarized 8Li nuclei has been measured. For the time-reversal violating triple correlation parameter we find R=(0.9+/-2.2)x10(-3). This result is in agreement with the standard model and yields improved constraints on exotic tensor contributions to the weak interaction. Combined with other experimental results and using a model for the coupling constants, a new limit for the mass of a possible scalar leptoquark, m(LQ)>560 GeV/c(2) (90% C.L.), is obtained.
Antibodies may be viewed as adaptor molecules that provide a link between humoral and cellular defence mechanisms. Thus, when antigen-specific IgG antibodies form antigen/antibody immune complexes the effectively aggregated IgG can activate a wide range of effector systems. Multiple effector mechanisms result from cellular activation mediated through a family of IgG-Fc receptors differentially expressed on leucocytes. It is established that glycosylation of IgG-Fc is essential for recognition and activation of these ligands. IgG antibodies predominate in human serum and most therapeutic antibodies are of the IgG class. The IgG-Fc is a homodimer of N-linked glycopeptide chains comprised of two immunoglobulin domains (Cgamma2, Cgamma3) that dimerise via inter-heavy chain disulphide bridges at the N-terminal region and non-covalent interactions between the C-terminal Cgamma3 domains. The overall shape of the IgG-Fc is similar to that of a "horseshoe" with a majority of the internal space filled by the oligosaccharide chains, only attached through asparagine residues 297.To investigate the influence of individual sugar (monosaccharide) residues of the oligosaccharide on the structure and function of IgG-Fc we have compared the structure of "wild-type" glycosylated IgG1-Fc with that of four glycoforms bearing consecutively truncated oligosaccharides. Removal of terminal N-acetylglucosamine as well as mannose sugar residues resulted in the largest conformational changes in both the oligosaccharide and in the polypeptide loop containing the N-glycosylation site. The observed conformational changes in the Cgamma2 domain affect the interface between IgG-Fc fragments and FcgammaRs. Furthermore, we observed that the removal of sugar residues permits the mutual approach of Cgamma2 domains resulting in the generation of a "closed" conformation; in contrast to the "open" conformation which was observed for the fully galactosylated IgG-Fc, which may be optimal for FcgammaR binding. These data provide a structural rationale for the previously observed modulation of effector activities reported for this series of proteins.
Repetitive inhibition of oxidative phosphorylation is an established model of neurodegeneration. In contrast, a single mild treatment can be neuroprotective-chemical preconditioning. Repetitive chemical inhibition of oxidative phosphorylation may thus be a tool to study deterioration and improvement of cellular hypoxic tolerance and subsequent differential regulation of cellular responses in the same model. We investigated murine hippocampal function upon repetitive intraperitoneal injections of 3-nitropropionate (3-NP; 20 mg/kg body weight), an inhibitor of mitochondrial complex II. With a 2-day interval of repetitive in vivo treatment with 3-NP, posthypoxic recovery of population spike amplitude was below control. In contrast, even after nine in vivo treatments with 3-NP at 4-day intervals, an almost complete recovery of population spike amplitude was observed. Nerve growth factor (NGF) as assessed by ELISA and expression of beta-amyloid precursor protein (APP) mRNA increased upon nine treatments at 2-day intervals, but remained at control levels with 4-day intervals. In contrast, brain-derived neurotrophic factor (BDNF) as assessed by ELISA increased with the latter treatment. Expression of mRNA for adenosine-A1 and -A3 receptors and endothelial and neuronal nitric oxide synthase remained at control level for both treatment intervals. We conclude that the time interval between mild, subclinical repetitive inhibition of oxidative phosphorylation determines hippocampal neuronal impairment and integrity and modulates NGF and BDNF differently. Decreased hypoxic tolerance and increased APP expression upon repetitive inhibition of oxidative phosphorylation at short time intervals may thus trigger a vicious cycle and be a cofactor for neuronal dysfunction in cerebral hypoxia and neurodegenerative diseases.
OBJECTIVES: evaluation of urgent carotid artery surgery with new diagnostic techniques and changing surgical considerations at a university hospital. DESIGN, MATERIAL AND METHODS: prospective monitoring and assessment of outcome in 67 patients who underwent urgent carotid surgery because of symptomatic extracranial carotid artery involvement. Patients were examined via the stroke unit: duplex sonography was mandatory for diagnosis of extracranial carotid artery disease, as was proof of an open middle cerebral artery (MCA). Assessment of intracerebral damage followed CT or MR imaging procedures. Perioperative and surgical management was standardized. Neurological impairment was assessed pre-, postoperatively and at follow-up using the Rankin scale. "Urgent" was defined as "immediate" after the final diagnostic step had been performed. RESULTS: within a period of 26 months 67 symptomatic patients (58% stroke, 42% TIA) underwent urgent carotid surgery. Median time from admission to surgery was 2 days. In all but five cases flow through the ICA could technically be restored (93%). Thirty-day mortality was 3% and disease-related morbidity 13%. The one and two year survival rates were 92 and 90%, respectively. No ipsilateral recurrent stroke occurred during follow-up. CONCLUSIONS: clinical decision-making based on stratified diagnostic workup by means of extra- and intracranial as well as intracerebral hemodynamics using new imaging techniques may select patients who will benefit more from urgent surgery than from conservative management.
PURPOSE: To investigate the DNA-proportional distribution of radiation-induced chromosome aberrations for all chromosomes of a male and a female human karyotype. MATERIALS AND METHODS: Metaphases were prepared from whole blood cultures obtained from two healthy donors and set up after irradiation with 3 Gy 220 kV X-rays. Single whole-chromosome FISH painting simultaneously with pancentromeric DNA painting were performed separately for each chromosome of the human karyotype. One thousand exclusively first-division metaphases were analysed per chromosome and donor. After statistical analysis, the data obtained were compared with theoretically expected values. RESULTS: All aberration types (translocations, dicentrics) showed deviations from a DNA-proportional distribution. For both donors, chromosomes 2 and 3 exhibited significantly less and chromosome 4 more symmetrical translocations than expected. Chromosomes 15 and 22 showed more symmetrical translocations than predicted for one of the two donors. Less dicentrics than expected became apparent for chromosomes 2, 3 and 18, while more dicentrics were seen for chromosomes 15, 16 and 17. Moreover, chromosomes 4, 14 and 22 showed a significant deviation from the theoretically expected 1:1 ratio of the yields of symmetrical translocations to the yields of dicentrics. CONCLUSION: The results from the whole-chromosome complement in two different donors confirmed published data from the analysis of single chromosomes that some human chromosomes were not involved in radiation-induced dicentrics and symmetrical translocations proportional to their DNA content. This must be taken into account if chromosome subsets for dose reconstruction are selected or if whole genomic frequencies have to be calculated from partial genome analysis.
OBJECTIVE: We investigated the effects of a popular modified juice fasting program on lipid metabolism. VOLUNTEERS AND METHODS: 5 healthy, nonobese, male volunteers fasted for 8 days. Daily energy intake was limited to 150-300 kcal/d solely as carbohydrates (vegetable and fruit drinks). Physical activity was maintained as before. At baseline, on days 2, 3, and 8 during fasting, and on days 2 and 8 after fasting, serum lipids, lipoproteins, and insulin were investigated. RESULTS: Juice fasting resulted in bi-phasic changes: Until day 2 and 3 triacylglycerols (TG), very low-density lipoprotein apolipoprotein B (VLDL apo B), and insulin decreased by 52, 51, and 65% respectively, while nonesterified fatty acids (NEFA), low-density lipoprotein (LDL) apo B, and LDL cholesterol increased by 363, 38, and 35%. Between day 3 and 8 NEFA increased; TG and insulin increased as well, but remained below baseline values, and LDL cholesterol normalized. After 8 days juice fasting significant changes (p < 0.05) compared to the baseline were found only for free cholesterol (-10%), phospholipids (-14%), apo AI (-9%), apo AII (-11%), insulin (-42%), C-peptide (-57%), and NEFA (+535%, p = 0.0001). Total cholesterol decreased by 9% (n.s.) after 8 days. One week after the ending of fasting all parameters returned to normal. CONCLUSION: Contrary to total fasting and fasting with limited physical activity, 8 days juice fasting without limitation of physical activity results in a decrease of free cholesterol and an only initial increase of LDL cholesterol. After 8 days insulin, TG, and VLDL are still lower than at baseline, however, they have increased compared to the initial phase, probably counterregulatory to a further increase of NEFA.
BACKGROUND: Several studies have been performed in tumour patients to analyse the immunological response to mistletoe extracts. Considering the fact that these extracts are given subcutaneously in most instances, the kind of application resembles a typical immunization schedule. We therefore wanted to see how those extracts act on immunocompetent cells of healthy individuals hoping that this kind of provocation test may give new informations about a more specific application of these extracts in certain diseases. SUBJECTS/METHODS: 47 healthy individuals were exposed for twelve weeks either to Iscador Quercus special (IQ) known to be rich in mistletoe lectin (ML)-1 (n = 16), to Iscador Pini (IP) being poor in ML-1 but enriched in viscotoxins (n = 15), or to placebo (physiological saline) (n = 16) in a randomised, double-blinded placebo-controlled study. Humoral immunoreactivity was analysed by measuring antibodies towards the two compounds ML-1 and viscotoxin VA2 (VA2). Sera were collected in intervals of four weeks up to week 12 and again three months after last exposure. RESULTS: None of the subjects had antibodies to ML-1 or VA2 before exposure. In week 12, anti-ML-1 antibodies of the IgG-type were found in all 16 IQ-treated individuals but only 6 of the 15 probands exposed to IP. In contrast, anti-VA2 IgG-antibodies could be detected in all individuals of both groups. The antibodies were preferentially of the IgG1 and IgG3 type while antibodies of the IgA and IgM type were produced only in a few probands. Antibodies of the IgE-type occurred only in the IQ-exposed individuals and were directed against ML-1 but not VA2. None of the probands receiving placebo developed antibodies to ML-1 or VA2. Severe side effects were not observed in any of the probands. CONCLUSIONS: These data obtained in healthy individuals clearly indicate that IQ and IP-extracts can induce antigen-specific humoral responses. They may, therefore, provide, a solid basic for the evaluation of the humoral immune response in disease states.
UNLABELLED: Long-term results after carotid reconstruction in patients with completed stroke caused by cerebrovascular occlusive disease. BACKGROUND AND OBJECTIVE: In patients with completed stroke caused by cerebrovascular occlusive disease the reconstruction of high grade carotid artery stenosis is discussed as prophylaxis for prevention of recurrent stroke. The operative complications of all patients who underwent surgery for carotid occlusive disease in the Heinrich Heine University between 1990 and 1999 were evaluated in this study. PATIENTS AND METHODS: We present the results of 596 reconstructions in 537 patients (404 men, 133 women; mean age 64,5 plus minus 9,4 years). The operative technique of choice was thromboendarterectomy of the carotid bifurcation with vein-patch closure. RESULTS: A postoperative ipsilateral neurological deficit was observed in 41 patients (6,9 %): 4,7 % permanent, 2,2 % transitory. Thirtyeight percent of the permanent deficits appeared after reconstructions performed within six weeks after stroke and only 9 % after surgery between six and twelve weeks. The in-hospital mortality was 0,7 % for neurological and 1,0 % for cardiopulmonary complications. During long-term follow-up (mean follow-up time 50 plus minus 34 months) only 17 (3,7 %) of 462 patients, which could be evaluated, presented with a new neurological event for the reconstructed side. Fifty-eight percent had none or minimal neurological deficits. 115 Patients (24,0 %) died during follow-up. CONCLUSION: Even after completed stroke carotid reconstruction can be carried out successfully in selected patients with an acceptable complication rate in prophylaxis of recurrent stroke. In our retrospective study the optimal time for surgery seems to be between six and twelve weeks after stroke, but new imaging techniques may alter in the future the time window for operation in patients with an unstable neurological situation early after stroke. The reduction of social mobility and the high mortality in follow-up in correlation to patients without stroke are mostly related to accompanying severe cardiopulmonal risk factors.
The etiology of Transient Global Amnesia (TGA) is still obscure. Diffusion-Weighted-Imaging (DWI) provides conflicting evidence concerning a possible vascular ischemic cause in mesiotemporal structures including the hippocampal region. The question remains open whether conflicting observations resulted from different observation times. DWI was performed at a time interval with known sensitivity for detection of ischemia. Ten patients (5 male, 5 female; mean age of 63 +/- 9, range 41-71 years) with typical TGA were investigated at an average delay of 18 hours (range 6 to 44 hours) between onset of symptoms and magnetic resonance imaging (transversal DW-, T1W- and T2W-MRI). Five patients received apparent-diffusion-coefficient (ADC)-mapping. Cerebrovascular studies (ECG, TTE and extra/transcranial dopplersonographic and duplexultrasonic investigation) and EEG were normal in all patients. DW-MRI-sequences and ADC-maps, if performed, were normal in all patients. Conventional T2W-MRI in 3 out of 10 patients showed microangiopathic subcortical changes and lacunar strokes of older origin. We conclude that TGA does not result from a vascular ischemic etiology in the majority of cases.
It is being discussed whether impairment of energy metabolism is a final common pathway of neurodegeneration or initiates the neurodegenerative cascade. The goal was to investigate hypoxic tolerance and oxidative energy metabolism in 4-month-old, presymptomatic B6-Tg(ThylAPP)23Sdz (APP23) mice, a transgenic mouse model of Alzheimer's disease. Posthypoxic recovery of the population spike amplitude in hippocampal region CA1 upon stimulation of Schaffer collaterals in region CA3 (15 min hypoxia, 45 min recovery) was 43+/-46% (mean+/-S.D.) vs. 19+/-35% (P<0.05) in slices from wild-type and transgenic animals, respectively. Fluorescence lifetime sensitive spectroscopy of NADH in the CA1 pyramidal cell layer (gate set for detection of protein-bound NADH) showed a wavelength maximum at 455.3+/-1.6 nm (mean+/-S.D.) in controls and 453.5+/-2.4 nm (P<0.05) in mutants. We conclude that hypoxic tolerance is impaired in presymptomatic APP23 mice and occurs prior to extracellular deposition of amyloid plaques. Impaired energy metabolism may thus partake in initiating the neurodegenerative cascade in a transgenic model of Alzheimer's disease. The blue shift of the spectrum of NADH in mutant mice indicates an altered protein microenvironment of energy metabolism under control conditions.
We examined the role of the posterior division of the paraventricular nucleus of the thalamus (pPVTh) in habituation of hypothalamic-pituitary-adrenal (HPA) responses to repeated restraint. Habituation refers to the decrement in HPA activity that occurs with repeated exposure to the same or homotypic stressor. To date, the pPVTh has been shown to inhibit the enhanced or facilitated HPA responses to novel, heterotypic restraint in previously chronically cold stressed rats. We hypothesized that the pPVTh also inhibits HPA activity under conditions of habituation. In the first experiment, we lesioned the pPVTh and examined adrenocorticotropic hormone (ACTH) and corticosterone responses to the first or eighth restraint exposure. In sham-lesioned rats, we found lower ACTH and corticosterone responses to the eighth period of 30 min restraint compared to the first exposure, evidence for habituation. In pPVTh-lesioned rats, there was no difference in ACTH and corticosterone responses to the eighth compared to the first restraint exposure. Therefore, pPVTh lesions prevented the habituation of HPA responses to repeated restraint. In the second experiment, we examined whether habituation to restraint is observable in response to an acute, single restraint on day 28 in sham and pPVTh lesioned rats that were exposed to restraint only on days 1 through 8. In this experiment, we replicated the results from the first experiment, and found evidence that habituation to restraint can be observed weeks after chronic stress has been terminated. Furthermore, pPVTh lesions had no additional effects on HPA responses to acute stress on day 28. In summary, pPVTh lesions inhibit habituation of HPA activity to a homotypic stressor, without altering HPA responses to the first restraint. Thus, the intact pPVTh inhibits HPA activity under conditions of habituation, as well as facilitation, and represents an important regulator of HPA activity under conditions of chronic stress.
Usage of mobile phones is rapidly increasing, but there is limited data on the possible effects of electromagnetic field (EMF) exposure on brain physiology. We investigated the effect of EMF vs. sham control exposure on waking regional cerebral blood flow (rCBF) and on waking and sleep electroencephalogram (EEG) in humans. In Experiment 1, positron emission tomography (PET) scans were taken after unilateral head exposure to 30-min pulse-modulated 900 MHz electromagnetic field (pm-EMF). In Experiment 2, night-time sleep was polysomnographically recorded after EMF exposure. Pulse-modulated EMF exposure increased relative rCBF in the dorsolateral prefrontal cortex ipsilateral to exposure. Also, pm-EMF exposure enhanced EEG power in the alpha frequency range prior to sleep onset and in the spindle frequency range during stage 2 sleep. Exposure to EMF without pulse modulation did not enhance power in the waking or sleep EEG. We previously observed EMF effects on the sleep EEG (A. A. Borbély, R. Huber, T. Graf, B. Fuchs, E. Gallmann and P. Achermann. Neurosci. Lett., 1999, 275: 207-210; R. Huber, T. Graf, K. A. Cote, L. Wittmann, E. Gallmann, D. Matter, J. Schuderer, N. Kuster, A. A. Borbély, and P. Achermann. Neuroreport, 2000, 11: 3321-3325), but the basis for these effects was unknown. The present results show for the first time that (1) pm-EMF alters waking rCBF and (2) pulse modulation of EMF is necessary to induce waking and sleep EEG changes. Pulse-modulated EMF exposure may provide a new, non-invasive method for modifying brain function for experimental, diagnostic and therapeutic purposes.
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Selected waste management scenarios were evaluated with regard to the goals of the Austrian Waste Management Act, taking into account long-term environmental protection and resource conservation as well as costs. Municipal solid waste (MSW) and sewage sludge have been chosen as the system inputs. The scenarios were compared to the status-quo scenario by combining Material Flow Analysis (MFA) and economic evaluation methods. Both, welfare-oriented Cost-Benefit Analysis (CBA) and Modified Cost-Effectiveness Analysis (MCEA) were applied for this assessment. Unlike CBA, MCEA takes into consideration long-term impacts of landfilled material in non-monetary terms. The results of the CBA correspond to those of the MCEA. Both evaluation methods confirm: If long-term effects are taken into account with the same weight irrespective of when they occur, the Austrian goals of waste management are reached more efficiently by thermal waste treatment scenarios than by mechanical-biological treatment scenarios or by landfilling without pre-treatment.