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Biomedical subjects

R Burger

Publications and source records attributed to R Burger.

At least 73 records · Page 4Linked to original sources
PubMed1995

Magnetic brain stimulation: safety studies.

We describe short-term and long-term safety studies after low repetition rate magnetic brain stimulation in 10 normal subjects. We obtained quantitative EEG data, psychometric test results, serum prolactin and cortisol levels before and after brain stimulation. EEG and psychometric data were also obtained in 5 of these subjects 16-24 months after the initial experiment. Short- and long-term studies did not show any deleterious effects. Randt delayed recalls, however, showed a transient reduction in the score immediately after stimulation which resolved on retesting in 2 weeks. To address the question of fatigue we repeated Randt tests in 4 subjects before and after magnetic brain stimulation but without the other extensive psychometric, EEG and blood tests. Pre- and post-stimulation scores on this occasion showed no significant difference in these 4 subjects suggesting that the transient changes in the previous Randt score were related to fatigue. We conclude that single-pulse magnetic brain stimulation has no deleterious effects after magnetic brain stimulation.

Adult↗
PubMed1995

Therapy with OKT3 monoclonal antibody in refractory T cell acute lymphoblastic leukemia induces interleukin-2 responsiveness.

Administration of cytokines to patients with leukemia or lymphoma may recruit dormant malignant cells into cell cycle and thus make them more susceptible to chemotherapy. We treated a patient with refractory T cell acute lymphoblastic leukemia (ALL) with OKT3 monoclonal antibody and observed a dramatic but transient decrease of lymphoblasts. The T ALL cells were rather mature by morphology and immunophenotyping, expressing CD7, CD4, CD8 and CD3 surface antigens and nuclear TdT. Cytogenetic analysis revealed inversion of chromosome 14(q11q32.1). A total of 500 mg OKT3 (maximum dose 50 mg/day) was given. A decrease of lymphoblasts in the blood and a reduction of spleen size was observed. Complement levels dropped remarkably. Despite increasing serum levels of tumor necrosis factor, treatment was well tolerated overall. CD3 therapy induced strong IL-2 responsiveness of the lymphoblasts. Thus, OKT3 antibody treatment not only significantly decreased CD3-positive tumor cells, but also induced IL-2-mediated proliferation. This may also allow sequential application of CD3 and IL-2 to render certain T cell tumors more susceptible to chemotherapy.

Adult↗
PubMed1995

High dose selegiline augments striatal ubiquinol in mouse: an indication of decreased oxidative stress or of interference with mitochondrial respiration? A pilot study.

The effects of unspecific doses of the irreversible monoamine oxidase inhibitor selegiline on alpha-tocopherol, alpha-tocopherolquinone, ubiquinol and ubiquinone were studied in frontal cortex, hippocampus and striatum of male C57BL/6 mice 4 h and 96 h after a single or six injections of selegiline (100 mg/kg body weight, i.p.), respectively. Inhibition of monoamine oxidase was confirmed by activity measurements of its isoforms A and B in brain stem nuclei and striatum as well as by determination of striatal levels of dopamine and its major metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid. In general, levels of alpha-tocopherol were not altered and levels of alpha-tocopherolquinone were below the detection limit. However, 96 h following selegiline, levels of ubiquinols 9 and 10 were significantly increased, whereas levels of ubiquinones 9 and 10 concomitantly decreased in the striatum. Concentrations of ubiquinols and ubiquinones in frontal cortex and hippocampus were unchanged 96 h following selegiline. These data suggest that selegiline affects the striatal redox ratio of ubiquinol to ubiquinone which is important for cellular antioxidant defense and mitochondrial electron transfer.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Effect of lipoic acid on redox state of coenzyme Q in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and diethyldithiocarbamate.

We investigated the effects of a combined treatment of male C57Bl/6 mice with diethyldithiocarbamate and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the absence or presence of different forms of lipoic acid (Thioctacid TR; commonly used for treatment of diabetic polyneuropathies) on levels and redox states of alpha-tocopherol and coenzyme Q in vivo and on activities of various enzymes of energy metabolism ex vivo. Treatment of mice with diethyldithiocarbamate plus MPTP resulted in a decrease in dopamine (67%) and its major metabolites dihydroxyphenylacetic acid (38%) and homovanillic acid (37%) in striatum. alpha-Tocopherol levels were unaltered in striatum; however, the reduced forms of coenzyme Q were decreased in frontal cortex and hippocampus following diethyldithiocarbamate plus MPTP. In frontal cortex activity of NADH dehydrogenase was significantly inhibited by diethyldithiocarbamate plus MPTP ex vivo, suggesting that the neurotoxic metabolite of MPTP, 1-methyl-4-phenylpyridinium ion, is acting in brain regions other than striatum as well. Lipoic acid, administered 6 times, each at 90 min prior to MPTP, could not restore dopamine in striatum but in contrast maintained a normal ratio of the reduced form to the oxidized form of coenzyme Q, suggesting an interaction of lipoic acid with energy metabolism which seems, however, not only to be due to an activation of pyruvate dehydrogenase.

Animals↗
PubMed1994

Interleukin-6 production in B-cell neoplasias and Castleman's disease: evidence for an additional paracrine loop.

Functioning as a B-cell growth and differentiation factor, interleukin-6 (IL-6) may play an important role in the pathophysiology of B-cell tumors. The capacity for IL-6 secretion was evaluated in 58 patients with various B-cell leukemias/lymphomas and in four patients with Castleman's disease (CMD). Cell populations from various sites including peripheral blood, bone marrow, lymph nodes, and osteolytic bone lesions were cultured and tested for spontaneous or IL-1 beta/TNF alpha-induced IL-6 production in a sensitive bioassay. No significant IL-6 levels were released by the tumor cells in any of the B-cell leukemias or lymphomas tested, including hairy cell leukemia (HCL) and B-cell chronic lymphocytic leukemia (B-CLL). In contrast, purified malignant plasma cells were found to secrete IL-6, strengthening the idea that an autocrine pathway for growth regulation in multiple myeloma (MM) exists. For the first time, in several patients with CMD, peripheral blood cells were shown to produce extremely high levels of IL-6, the pathogenetic significance of which remains to be elucidated. However, similar observations were very occasionally made in MM patients. Therapy with corticosteroids strongly inhibited this IL-6 production. These data provide evidence for autocrine and possibly an additional paracrine regulatory loop in plasma cell neoplasias and CMD.

Adrenal Cortex Hormones↗
PubMed1994

Tracheostomy in children.

We reviewed the records of 108 patients who had a tracheostomy performed over a 10-year period from July 1979 to April 1989. Median age at tracheostomy was 6 months (1 week-15 years). Indications for surgery were acquired subglottic stenosis (31.4%), bilateral vocal cord paralysis (22.2%), congenital airway malformations (22.2%) and tumours (11.1%). No epiglottis and no emergency situation had to be managed by tracheostomy. Operation was uneventful in all, but 8 patients (7.4%) developed a pneumothorax in the postoperative period. Twenty-one (19.5%) had severe complications during the cannulation period (tube obstruction in 11 patients with cardiorespiratory arrest in 4; dislocation of the tube in 6 patients). Fifteen patients (13.8%) had severe complications after decannulation (2 had a cardiorespiratory arrest); all 15 had to be recannulated. At the end of the study period 85 patients (78.7%) were successfully decannulated with a median period of tracheostomy of 486 days (8 days-6.6 years). The median hospital stay was 159 days (13 days-2.7 years). All patients could be discharged. Eight patients (7.4%) died but no death was related to tracheostomy. In summary the mortality rate is lower than reported in previous reviews and tracheostomy is a safe operation even in small children but cannula-related complications may lead to life-threatening events. The management of tracheostomized small children and infants in a highly staffed and monitored intensive care unit has allowed better handling of complications and has resulted in a reduction in cannula-related deaths.

Adolescent↗
PubMed1994

T-lymphocyte responses in guinea pigs vaccinated with foot-and-mouth disease virus.

The guinea pig provides an alternative experimental model for analysis of the immune response against foot-and-mouth disease virus (FMDV). The cellular immune response against FMDV in this experimental animal is unknown and was analyzed by in vivo and in vitro studies. In guinea pigs immunized with an FMDV A5 vaccine, a marked change in T-lymphocyte count appeared. For analyzing which functional T-cell compartment was affected, immunofluorescence studies, using monoclonal antibodies directed against differentiation antigens on guinea pig lymphoid cells, were performed. The proliferating T-cells were predominantly CD4-positive and, therefore, helper cells. T-cells from these animals were re-stimulated in vitro with homologous inactivated virus. The antigen-specific proliferative response of the T-cells in vitro was measured using the thymidine incorporation assay. A proliferative response to FMDV was observed that depended on the dose of the antigen. High concentration of virus had an inhibitory effect on T-cell proliferation. These data indicate that the guinea pig is a useful model for analysis of T-cell mediated mechanisms in the pathogenesis and immunity of foot-and-mouth disease.

Animals↗
PubMed1994

The acute lymphoblastic leukaemia cell line SEM with t(4;11) chromosomal rearrangement is biphenotypic and responsive to interleukin-7.

A cell line, designated SEM, was established from the peripheral blood of a 5-year-old girl in relapse with acute lymphoblastic leukaemia (ALL). Both the lymphoblasts of the patient and the cells of the cell line SEM showed the t(4;11) chromosomal rearrangement. The analysis of the immunophenotype of the SEM cell line revealed the B-cell differentiation antigens CD19, CD22 and CDw75 in the absence of CD20, CD24 and immunoglobulin expression. Besides B-lineage antigens, SEM cells were positive for the myeloid antigens CD13, CD15, CD33 and CDw65. Immunogenotypic analysis of SEM cells showed a monoclonal rearrangement of immunoglobulin heavy-chain (IgH). T-cell receptor (TCR) gamma and delta genes. Addition of interleukin (IL)-7 promoted the growth of the patient's lymphoblasts in culture and enhanced the proliferation of SEM cells. The SEM cells also express messenger RNA (mRNA) for the IL-7 receptor (IL-7R), but no evidence for autocrine production of IL-7 by the cell line was found. Addition of IL-4, tumour necrosis factor (TNF)-alpha, interferon (IFN)-alpha, or IFN-gamma resulted in a profound inhibition of SEM growth. Thus, these cytokines may have important growth regulatory activities for biphenotypic leukaemic ALL cells.

Antigens, CD↗
PubMed1994

Influence of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, lipoic acid and L-deprenyl on the interplay between cellular redox systems.

For several years there is controversy concerning the toxic potency of reaction products catalyzed by monoamine oxidase in neurodegenerative processes. There is uncertainty whether products of catecholamine oxidation are pathogenetically relevant factors for neuronal cell death in Parkinson's disease. To date products responsible for impairment of biochemical functions essential for cell viability are not yet identified, and the primary site of damage within the cell is unknown. Ammonia, aldehydes and hydrogen peroxide are formed via monoamine oxidase catalyzed oxidations of primary amines. But which of them, if any, is damaging to the cell? We discuss some aspects of the oxidative stress theory of cell degeneration in relation to toxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and to monoamine oxidation. Furthermore, we consider possible functional relationships of mitochondrial electron transfer reactions, toxicity of MPTP and MAO activity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

The Dübendorf Study: a population-based investigation on normal values of blood pressure self-measurement.

There is evidence that self-measurement of BP increases precision, reproducibility and prognostic value of BP measurement. However, generally accepted normal values for BP values obtained by self-measurement are still missing. The present study was undertaken to investigate differences between office and self-measured blood pressure; 503 randomly selected inhabitants (265 men and 238 women, age 20-90 years, mean age 46.5 +/- 12.9 years) of the small town of Dübendorf in Switzerland were studied. The subjects were not preselected according their BP levels, only patients taking antihypertensive drugs were excluded. Self-measurement was performed at home by the subjects during 14 days in the morning between 6 and 8 am and in the evening between 6 and 8 pm (mean of 26.7 measurements). Office BP was taken before and after the two week period. Mean office BP (130.0 +/- 16.5/82.1 +/- 11.1 mmHg) was significantly (P < 0.01) higher than mean self-measured BP (123.1 +/- 14.6/77.6 +/- 10.7 mmHg). There was no significant difference between first and second office BP measurement. Morning self-measured BP was lower than evening pressure (delta 4.0/1.4 mmHg, both P < 0.01) and the mean was taken for comparison with office BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Complement fragment C3a stimulates Ca2+ influx in neutrophils via a pertussis-toxin-sensitive G protein.

The signal pathways of neutrophils following stimulation with the complement fragment C3a (C3a) were studied in neutrophils and compared to the pathways activated by complement fragment C5a (C5a). Analysis of polyphosphoinositol lipid turnover showed that C5a, but not C3a, activated phosphatidylinositol-bisphosphate-3-kinase (PtdInsP2 3-kinase) indicating that different signal pathways are activated by the two anaphylatoxins. To examine whether C3a stimulated Ca2+ transients, cytosolic free Ca2+ levels were analyzed in Fluo-3-labelled neutrophils by flow cytometry. C3a stimulated a fast and concentration-dependent increase of cytosolic free Ca2+. Comparison of the C3a response with that of C5a revealed a more pronounced C5a-triggered Ca2+ rise. Addition of EGTA to the extracellular buffer prior to stimulation did not significantly alter the initial Ca2+ rise at low C5a concentrations, but reduced the time course of the Ca2+ transients at high concentrations. In marked contrast, EGTA completely blocked the Ca2+ response stimulated by C3a in neutrophils labeled with either Indo-1/AM or Fluo-3. Preincubation of neutrophils with pertussis toxin inhibited both C3a- and C5a-stimulated Ca2+ transients, indicating the involvement of guanine-nucleotide-binding proteins (G proteins) in these processes. In order to examine whether the C3a receptor is coupled to G proteins, binding of guanosine 5'-O-(3-[35S]thiotriphosphate) ([35S]GTP[S]) to purified neutrophil plasma membranes was studied. Both C3a and C5a stimulated high-affinity binding of [35S]GTP[S] up to 1.5-fold and 3-fold, respectively. These data suggest that the two anaphylatoxins activate pertussis-toxin-sensitive G proteins, which then trigger different signal transduction pathways. C3a specifically stimulated Ca2+ influx from the extracellular medium, whereas C5a additionally activated the PtdInsP2 3-kinase and stimulated Ca2+ mobilization from intracellular stores.

Calcium↗
PubMed1993

Early pattern recognition in severe perinatal asphyxia: a prospective MRI study.

On the basis of MRI examinations in 88 neonates and infants with perinatal asphyxia, we defined 6 different patterns on T2-weighted images: pattern A--scattered hyperintensity of both hemispheres of the telencephalon with blurred border zones between cortex and white matter, indicating diffuse brain injury; pattern B--parasagittal hyperintensity extending into the corona radiata, corresponding to the watershed zones; pattern C--hyper- and hypointense lesions in thalamus and basal ganglia, which relate to haemorrhagic necrosis or iron deposition in these areas; pattern D--periventricular hyperintensity, mainly along the lateral ventricles, i.e. periventricular leukomalacia (PVL), originating from the matrix zone; pattern E--small multifocal lesions varying from hyper--to hypointense, interpreted as necrosis and haemorrhage; pattern F--periventricular centrifugal hypointense stripes in the centrum semiovale and deep white matter of the frontal and occipital lobes. Contrast was effectively inverted on T1-weighted images. Patterns A, B and C were found in 17%, 25% and 37% of patients, and patterns D, E and F in 19%, 17% and 35%, respectively. In 49 patients a combination of patterns was observed, but 30% of the initial images were normal. At follow-up, persistent abnormalities were seen in all children with patterns A and D, but in only 52% of those with pattern C. Myelination was retarded most often in patients with diffuse brain injury and PVL (patterns A and D).

Asphyxia Neonatorum↗
PubMed1993

Chronic lymphocytic leukemia cells induce non-T cells to produce IgE in the presence of interleukin-4.

Mononuclear cells from peripheral blood and bone marrow from patients with chronic lymphocytic leukemia (CLL) were cultured with interleukin-4 (IL-4) alone or with IL-4 and hydrocortisone (HC) in order to induce IgE synthesis. From a total of 29 experiments with the cells of 17 different donors an IgE secretion was observed only twice. Even in those two cases the IgE was found to be not monoclonal. The additional stimulation of CLL cells by polyclonal B cell activators induced IgM but not IgE production. When CLL cells were cocultured with monocyte-enriched cell preparations (M phi) in the presence of IL-4 and HC, a substantial IgE secretion could be obtained, which again consisted of both IgE kappa and IgE lambda. Since the irradiation of the M phi but not of the CLL cells abolished the formation of IgE, it is likely that the IgE production resided in the contaminating B cell population of the M phi. When the M phi were replaced by T cell-depleted peripheral blood mononuclear cells (non-T cells), irradiated as well as formaldehyde fixed CLL cells were able to stimulate non-T cells to secrete IgE in the presence of IL-4 or to potentiate IL-4- and HC-induced IgE formation. Furthermore, the coculture of irradiated pure CLL cells and purified B cells induced not only IgE but also IgG and IgM production and B cell proliferation in the presence of lymphokines. Our findings suggest that CLL cells, contrary to current opinion, cannot be induced to produce IgE.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗
PubMed1993

Hemodynamic effects of sodium bicarbonate in critically ill neonates.

OBJECTIVE: To analyze the cardiovascular effects of sodium bicarbonate in neonates with metabolic acidosis. DESIGN: Prospective, open, non-randomized, before-after intervention study with hemodynamic measurements performed before and 1, 5, 10, 20, and 30 min after bicarbonate administration. SETTING: Neonatal intensive care unit, tertiary care center. PATIENTS: Sequential sample of 16 paralysed and mechanically ventilated newborn infants with a metabolic acidosis (pH < 7.25 in premature and < 7.30 in term infants, base deficit > -8). INTERVENTION: An 8.4% sodium bicarbonate solution diluted 1:1 with water (final osmolality of 1000 mOsm/l) was administered in two equal portions at a rate of 0.5 mmol/min. The dose in mmol was calculated using the formula "base deficit x body weight (kg) x 1/3 x 1/2". MEASUREMENTS AND RESULTS: Sodium bicarbonate induced a significant but transient rise in pulsed Doppler cardiac output (CO) (+27.7%), aortic blood flow velocity (+15.3%), systolic blood pressure (BP) (+9.3%), (+14.6%), transcutaneous carbon dioxide pressure (PtcCO2) (+11.8%), and transcutaneous oxygen pressure (PtcO2) (+8%). In spite of the PaCO2 elevation, pH significantly improved (from a mean of 7.24 to 7.30), and the base deficit decreased (-39.3%). Calculated systemic vascular resistance (SVR) (-10.7%) and diastolic BP (-11.7%) decreased significantly, while PaO2 and heart rate (HR) did not change. Central venous pressure (CVP) (+6.5%) increased only slightly. By 30 min after bicarbonate administration all hemodynamic parameters, with the exception of the diastolic BP, had returned to baseline. CONCLUSION: Sodium bicarbonate in neonates with metabolic acidosis induces an increase in contractility and a reduction in afterload.

Acidosis, Lactic↗
PubMed1993

Resuscitation after severe hypoxia in a young child: temporary isoelectric EEG and loss of BAEP components.

EEG and multimodality evoked potentials are currently used to ascertain brain death. We have observed electrocerebral silence (ECS) and loss of wave IV and V in BAEP in a 28-month-old child, 2 h after resuscitation from severe hypoxia, followed by reappearance of EEG activity and of waves IV and V (latencies and amplitudes within normal range) 18 h later. Temporary loss of EEG activity has been observed occasionally, while rapid reoccurrence of BAEP waves IV and V was unexpected and in contrast to the common observation, that rostro-caudal loss of BAEP waves is irreversible. This observation suggests that temporary loss of BAEP waves IV and V may occur and that caution is necessary in the interpretation of BAEP recorded immediately after a resuscitation.

Brain Death↗
PubMed1993

Squamous-cell carcinoma arising in a non-irradiated child with recurrent respiratory papillomatosis.

We describe a patient with recurrent respiratory papillomatosis (RRP) associated with human papilloma virus (HPV), who developed a fatal squamous cell carcinoma of the lung. At the age of 1 year he presented with hoarseness, dyspnoea and inspiratory stridor but the diagnosis of RRP was made only 1 year later. At the age of 4 years he was tracheostomized because of upper airway obstruction. In spite of multiple surgical excisions and topic treatment with 5-fluorouracil the papillomata extended to the lung parenchyma. At the age of 16 years he developed a squamous-cell carcinoma of the lung and died 4 months later. Transformation to pulmonary carcinoma is a rare complication in non-irradiated patients with lung papillomatosis. We found only 11 similar cases in the literature.

Adolescent↗
PubMed1993

The thiobarbituric acid assay reflects susceptibility to oxygen induced lipid peroxidation in vitro rather than levels of lipid hydroperoxides in vivo: a methodological approach.

Although the hypothesis of oxidative stress as a pathogenetic factor of neurodegenerative diseases became a matter of interest recently, direct evidence supporting this hypothesis is rare. The most prominent assay being currently used as an index for lipid peroxidation products in vivo is the thiobarbituric acid assay. Thiobarbituric acid reactive substances are mainly formed during the decomposition of lipid hydroperoxides in vitro. It is questionable however, that all species detectable with thiobarbituric acid are derived from in vivo preformed lipid hydroperoxides. These studies were undertaken to investigate the influence of autoxidation reactions on colour production during the acid heating stage of the assay. If driven aerobically, more than 90% of thiobarbituric acid reactive substances are newly generated in vitro during incubation at 95 degrees C for 75 min. This process can be enhanced by addition of ferric iron. Chain breaking antioxidants like butylated hydroxytoluene decrease colour formation in the absence or in the presence of iron. If driven anaerobically under argon, colour formation was only 10% of aerobically heated homogenates or lipid extracts of human brain tissue. These results may indicate that measurement of thiobarbituric acid reactive substances under the aerobic conditions described here reflects to a great extent the susceptibility of brain tissue or lipids to oxygen-induced formation of lipid hydroperoxides in vitro rather than degradation products of in vivo performed lipid hydroperoxides.

Aged↗