Biomedical subjects

C Burger

Publications and source records attributed to C Burger.

At least 55 records · Page 3Linked to original sources

PubMed1999

CoREST: a functional corepressor required for regulation of neural-specific gene expression.

Several genes encoding proteins critical to the neuronal phenotype, such as the brain type II sodium channel gene, are expressed to high levels only in neurons. This cell specificity is due, in part, to long-term repression in nonneural cells mediated by the repressor protein REST/NRSF (RE1 silencing transcription factor/neural-restrictive silencing factor). We show here that CoREST, a newly identified human protein, functions as a corepressor for REST. A single zinc finger motif in REST is required for CoREST interaction. Mutations of the motif that disrupt binding also abrogate repression. When fused to a Gal4 DNA-binding domain, CoREST functions as a repressor. CoREST is present in cell lines that express REST, and the proteins are found in the same immunocomplex. CoREST contains two SANT (SW13/ADA2/NCoR/TFIIIB B) domains, a structural feature of the nuclear receptor and silencing mediator for retinoid and thyroid human receptors (SMRT)-extended corepressors that mediate inducible repression by steroid hormone receptors. Together, REST and CoREST mediate repression of the type II sodium channel promoter in nonneural cells, and the REST/CoREST complex may mediate long-term repression essential to maintenance of cell identity.

Amino Acid Sequence↗

PubMed1999

Oral immunisation of swine with a classical swine fever vaccine (Chinese strain) and transmission studies in rabbits and sheep.

Seven experiments including a total of 47 pigs, 11 wild boars, 26 rabbits, 10 hares and 16 sheep were carried out to assess the efficacy, safety and transmission of the Chinese vaccine strain of the classical swine fever virus (CSFV) administrated by the oral route. Within 3 weeks after oral vaccination, a clear seroconversion occurred in the pigs. Six weeks after vaccination, vaccinated pigs were fully protected against a virulent challenge. The C-strain was not isolated from tonsils, spleen, lymph nodes, thymus, saliva, urine and faeces of pigs within 4 days after oral vaccination. In one experiment, susceptible pigs were placed in direct contact with vaccinated pigs. None of these contact-exposed pigs became serologically positive for CSFV antibodies. It is concluded that the C-strain induces protection in pigs when administrated by the oral route and is not shed by vaccinated pigs. Serum anti-CSFV antibodies developed in seven out of eight wild boars vaccinated by the oral route. No vaccine virus was detected in the spleen and tonsils of these animals. The results in wild boar were in accordance with those obtained in domestic pigs. Sheep did not show any clinical signs after oral vaccination while rabbits had moderate hyperthermia and growth retardation. No clinical response to oral immunisation in hares was detected. At the end of the experiment, no sheep had detectable serum antibodies against CSFV, whereas a few vaccinated rabbits and hares became seropositive. None of the contact-exposed rabbits and hares seroconverted. These data indicate that the C-strain is safe for sheep and as expected, moderately or not pathogenic for rabbits and hares. These efficacy and safety studies on oral vaccination with the C-strain under experimental conditions provide essential information for further studies in wild boars under experimental and field conditions, including assays with baits to control a CSF epidemic.

Administration, Oral↗

PubMed1999

[Are there guidelines for treatment of metacarpal fractures? Personal results and literature analysis of the last 12 years].

As the treatment of metacarpal fractures is today still a controversial subject, we conducted an analysis of the literature in order to present the different therapy guidelines, indications, and their results. The data from the follow-up of 1602 patients was taken from literature which dated from 1 January 1984 to 31 March 1996. A total of 522 patients who underwent surgery received K-wires, screws or external minifixateur. The conservative approaches ranged from immobilization to various methods of mobilization with different aids or without fixation of the fracture. The mobilization in a brace provided good to excellent results in 95% of the cases; however, the failure rate of therapy was 23% because of local bruises and skin necrosis (3%). The mobilization with handcast, tape etc. attained good to excellent results in 94% of the cases. Here, no complications occurred. Both the immobilization treatment and the surgery provided good to excellent results in 85% of the cases. The reposition of fractures of the fifth metacarpal was successful in only 15% of the cases. Fractures with dislocations below 30 degrees, a shortening of less than 5 mm, no rotational displacement or that below 10 degrees, no articular incongruency, and no relevant soft tissue trauma do not need surgery according to our results and should be treated with early mobilization as suggested by the survey. Beyond these limits a primary surgical therapy is justified. The immobilization of metacarpal fractures over a period of more than 3-4 weeks is not necessary.

Adult↗

PubMed1999

An integrated strategy for the process development of a recombinant antibody-cytokine fusion protein expressed in BHK cells.

Recombinant fusion proteins offer important new therapeutic approaches for the future. This report describes the use of three different genetic strategies (i.e. "mono-", "bi-" and "tri-cistronic" vectors) to achieve stable secretion from BHK cells of a glycosylated antibody-cytokine fusion protein designed for use in antitumour therapy. It describes selection of a robust and effective production cell line based on stability of secretion of the product, quality of mRNA and protein products and performance in in vitro bioassays for potency. The data obtained at this stage were utilised in the selection of a suitable candidate production cell line. The relative productivity and general performance of the cells in stirred tank and fixed bed culture systems indicated that a variety of cell culture technologies provided robust tools for production of a highly selected cell clone. Consistency of the product glycosylation was determined by analysis of released oligosaccharides using matrix-assisted laser desorption ionisation-time of flight mass spectrometry and high-performance anion exchange chromatography. These investigations showed consistent expression of three glycoforms of the fusion protein which varied in their relative proportions in different culture systems and at different time points in a fixed bed reactor with continuous perfusion. In conclusion, this study dealt with a range of important scientific and technical issues which are essential for regulatory approval and commercial success of a recombinant protein and elucidates some useful markers for process development for similar recombinant biologicals.

Animals↗

PubMed1999

Treatment of complete acromioclavicular dislocation: present indications and surgical technique with biodegradable cords.

We report a retrospective study of 48 patients with complete acromioclavicular dislocation (Tossy III). All patients (38 male; 10 female) with an average age of 33.4 years underwent surgery including PDS-augmentation. More than half of the injuries were caused by sport accidents. There were no complications during surgery. 87% of the patients were free of complaints and subjectively very satisfied with the surgical results. By radiological examination we diagnosed a subluxation of the clavicula in 25% of the cases and arthrosis in 17% of the cases. Assessment of subjective complaints, the clinical examination, and the radiological diagnostic according to the Taft Score (0-12 points) resulted in an average value of 10.2 points. The surgical intervention using PDS-cord augmentation in cases of complete acromioclavicular separation is a safe and economic method with a low complication rate. Advantages are possible early-functional treatment, no risk of movement of implants, and avoidance of metal removal.

Absorbable Implants↗

PubMed1999

[The MR tomographic imaging of uncomplicated secondary fracture healing exemplified by the distal radius fracture].

PURPOSE: To investigate the normal sequential MR-pattern of uncomplicated fracture healing within the first 6 weeks. METHODS: In 8 patients with distal radius fracture, 4 by 4 with and without intraarticular fracture, MR examinations were performed 3-4 days after the onset of fracture and after 1, 2, 3, 4, 5 and 6 weeks using the following techniques: T1-weighted spin echo, T2-weighted spin echo, T2 proton density weighted, STIR (short inversion time inversion recovery), T2-weighted turbo spin-echo and fast field echo (FFE, gradient echo). Sequential examinations were analysed regarding 1) the appearance of fracture line, 2) development of bone marrow signal, and 3) signal changes in surrounding soft tissue. Maximum contrast of bone marrow and soft tissue was measured. RESULTS: The fracture line in bone marrow was best detectable in FFE- and T2-weighted spin ech images during the first week and in T2-weighted fast spin echo and proton density-weighted images from the 2nd to 4th week. Beginning in the 5th-6th week an increase of signal intensity in the fracture gap was typical in all sequences except for T1-weighted spin echo. The contrast maximum of bone marrow and soft tissue, best detectable in STIR- and T2-weighted spin echo images, occurred in the 1st-2nd week. CONCLUSIONS: MRI shows a typical time-depending pattern of the fracture line, surrounding bone marrow and soft tissue in normal fracture healing. The degree of injury influences the development of signal changes.

Adult↗

PubMed1999

[Baker's cyst].

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Adult↗

PubMed1998

[Baker's cyst--current surgical status. Overview and personal results].

Baker's cysts were treated operatively in 19 patients in the Department of Traumatology of the University of Cologne from 1988 to 1997. The subjective and objective results were evaluated with a questionnaire and a clinical examination and sonography (follow-up: 95%). All patients were examined before surgery, sonography and X-ray of the knee were performed. We differentiated between the congenital primary cyst (39%), and the secondary form, which was always associated with an intraarticular lesion (61%). Arthroscopy was performed in all secondary forms of Baker's cyst. Postoperative complications were two reinterventions due to one hematoma and one effusion. Patient's evaluation of operation result was "excellent" in 61% and "good" in 39% of cases. All knee joints had a full range of motion. There was only one case of a recurrent cyst. The primary form of Baker's cyst has always to be extirpated, according to our clinical experience. The extirpation of the secondary Baker's cyst and the relevance of arthroscopy and treatment of the basic disease have to be discussed.

Adolescent↗

PubMed1998

Changes of cerebral blood flow during short-term exposure to normobaric hypoxia.

Decreased arterial partial oxygen pressure (PaO2) below a certain level presents a strong stimulus for increasing cerebral blood flow. Although several field studies examined the time course of global cerebral blood flow (gCBF) changes during hypoxia at high altitude, little was known about the regional differences in the flow pattern. Positron emission tomography (PET) with [(15)O]H2O was used on eight healthy volunteers to assess regional cerebral blood flow (rCBF) during short-term exposure to hypoxia corresponding to simulated altitudes of 3,000 and 4,500 m. Scans at the simulated altitudes were preceded and followed by baseline scans at the altitude of Zurich (450 m, baseline-1 and baseline-2). Each altitude stage lasted 20 minutes. From baseline to 4,500 m, gCBF increased from 34.4 +/- 5.9 to 41.6 +/- 9.0 mL x minute(-1) x 100 g(-1) (mean +/- SD), whereas no significant change was noted at 3,000 m. During baseline-2 the flow values returned to those of baseline-1. Statistical parametric mapping identified the hypothalamus as the only region with excessively increased blood flow at 4,500 m (+32.8% +/- 21.9% relative to baseline-1). The corresponding value for the thalamus, the structure with the second largest increase, was 19.2% +/- 16.3%. Compared with the rest of the brain, an excessive increase of blood flow during acute exposure to hypoxia is found in the hypothalamus. The functional implications are at present unclear. Further studies of this finding should elucidate its meaning and especially focus on a potential association with the symptoms of acute mountain sickness.

Adult↗

PubMed1998

PET with 18fluorodeoxyglucose and hexamethylpropylene amine oxime SPECT in late whiplash syndrome.

BACKGROUND: Many patients have cognitive abnormalities and psychological problems after whiplash injury to the cervical spine. To our knowledge, neuroradiologic imaging has not depicted brain damage that explains the symptoms. Parietotemporo-occipital perfusion deficits on hexamethylpropylene amine oxime (HMPAO) SPECT studies have been described among patients who have sustained whiplash injury. METHODS: We examined 13 patients with typical late whiplash syndrome (study group) using HMPAO SPECT, 18fluorodeoxyglucose (FDG) PET, and MRI of the brain and compared the findings with those for 16 control subjects who underwent FDG PET. RESULTS: In the study group, statistical parametric mapping revealed significantly decreased FDG uptake in the frontopolar and lateral temporal cortex and in the putamen. The frontopolar hypometabolism correlated significantly with scores of the Beck Depression Inventory. However, in individual cases, reliability in the depiction of hypometabolic areas was relatively low. No alterations were found in the parietotemporo-occipital area. In these areas, decreased uptake of HMPAO and FDG correlated with cortical mass. CONCLUSION: FDG PET did not allow reliable diagnosis of metabolic disturbances for individual patients. Therefore, we do not recommend FDG PET or HMPAO SPECT as a diagnostic tool in routine examinations of patients with late whiplash syndrome.

Adult↗

PubMed1997

Outbreak of Q fever in Lohra-Rollshausen, Germany, spring 1996.

Q fever is an acute (and sometimes chronic) febrile illness caused by the rickettsial organism Coxiella burnetii. The commonest animal reservoirs for C. burnetiiare cattle, sheep, and goats. Infected animals shed the organisms, which resist desiccation, i

Journal Article↗

PubMed1997

Requirements and implementation of a flexible kinetic modeling tool.

UNLABELLED: Kinetic (or compartment) modeling is a highly versatile tool for the analysis of experiments within living systems. In PET, it is essential for developing tracers, for assessing tracer behavior and for extracting quantitative information about the target process. However, tools to support the modeling tasks involved are not easily available. METHODS: This article presents a requirements analysis for kinetic modeling in PET. The interactive kinetic modeling tool KMZ implements many of these features. It facilitates model development by a set of predefined models and by the ease of introducing new models. Monte Carlo studies allow assessing parameter identifiability. The responses in the different compartments as well as the expected time-activity curve can be simulated for specific model configurations. For measured time-activity curves, model optimization can be performed by the Powell or the Marquardt algorithm. Both support weighted nonlinear least-squares fitting and allow optional constraints of parameter ranges. To further improve parameter estimation, the fitting of several regional time-activity curves can be coupled, resulting in lower standard errors for parameters common among regions. It is possible to highly automate the evaluation of study series and to forward the results into statistical analysis tools. RESULTS: The KMZ tool has proven highly suitable in evaluating data from different types of studies, and the intuitive user interface enables medical doctors to successfully perform routine evaluations after a short training period. CONCLUSION: A portable kinetic modeling tool with the described features would provide easy access to model development and may help consolidate kinetic modeling in clinical settings for well-defined applications.

Algorithms↗

PubMed1996

Hip fracture.

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Femur Head Necrosis↗

PubMed1996

[Image fusion in medical radiology].

Image fusion supports the correlation between images of two or more studies of the same organ. First, the effect of differing geometries during image acquisitions, such as a head tilt, is compensated for. As a consequence, congruent images can easily be obtained. Instead of merely putting them side by side in a static manner and burdening the radiologist with the whole correlation task, image fusion supports him with interactive visualization techniques. This is especially worthwhile for small lesions as they can be more precisely located. Image fusion is feasible today. Easy and robust techniques are readily available, and furthermore DICOM, a rapidly evolving data exchange standard, diminishes the once severe compatibility problems for image data originating from systems of different manufacturers. However, the current solutions for image fusion are not yet established enough for a high throughput of fusion studies. Thus, for the time being image fusion is most appropriately confined to clinical research studies.

Humans↗

PubMed1996

Xenopus spinal neurons express Kv2 potassium channel transcripts during embryonic development.

Developmentally regulated delayed rectifier potassium currents determine the waveform of the action potential in all Xenopus embryonic primary spinal neurons. To examine this developmental program at the molecular level, we have isolated Xenopus Kv2 potassium channel genes Kv2.1 and Kv2.2. Both genes induce functional heterologous expression of delayed rectifier potassium currents. Transcripts from both Kv2 genes are present in developing embryos; however, only Kv2.2 mRNA is detectable in embryonic spinal neurons. Notably, Kv2.2 transcripts localize to ventral spinal neurons, whereas previously described Kv1.1 transcripts are found in dorsal spinal neurons. Thus, spinal neuron subtypes express distinct potassium channel genes, yet they temporally coordinate functional expression of delayed rectifier potassium currents.

Amino Acid Sequence↗

PubMed1996

[Segmental displacement by callus distraction in extended tibial defects].

In open tibial fractures with defects over 4 cm, spongiosaplasty is considered to be insufficient. Since 1988 we have tried to apply Ilisarov's ideas of callus distraction in combination with modern external fixation devices and AO/ASIF implants. By August 1995, 15 patients with severe tibial fractures had been treated. The bone defect averaged 7 cm. Thus, more than 1 m of tubular bone was produced. Eleven male and 4 female patients, averaging 21.3 years in age, were given this treatment. The defect was caused by resection of a malignancy in 3 cases and a second- or third-degree open fracture in 12 cases, accompanied by osteomyelitis in 6 cases. Reconstruction required an average of 5.3 operations. The complication rate was 53%, and the median duration of treatment was about 1 year. The final results were excellent or good. Amputation could be avoided in all instances. This treatment is contra indicated if the patient exhibits a lack of compliance. There is a realistic chance of salvaging the limb in cases of severe soft tissue and bone defects. In terms of economical considerations, this treatment is cost effective. Physical integrity and mobility without aid is the important motivation for these patients.

Adolescent↗

PubMed1996

Tracer kinetic modelling of receptor data with mathematical metabolite correction.

Quantitation of metabolic processes with dynamic positron emission tomography (PET) and tracer kinetic modelling relies on the time course of authentic ligand in plasma, i.e. the input curve. The determination of the latter often requires the measurement of labelled metabolites, a laborious procedure. In this study we examined the possibility of mathematical metabolite correction, which might obviate the need for actual metabolite measurements. Mathematical metabolite correction was implemented by estimating the input curve together with kinetic tissue parameters. The general feasibility of the approach was evaluated in a Monte Carlo simulation using a two tissue compartment model. The method was then applied to a series of five human carbon-11 iomazenil PET studies. The measured cerebral tissue time-activity curves were fitted with a single tissue compartment model. For mathematical metabolite correction the input curve following the peak was approximated by a sum of three decaying exponentials, the amplitudes and characteristic half-times of which were then estimated by the fitting routine. In the simulation study the parameters used to generate synthetic tissue time-activity curves (K1-k4) were refitted with reasonable identifiability when using mathematical metabolite correction. Absolute quantitation of distribution volumes was found to be possible provided that the metabolite and the kinetic models are adequate. If the kinetic model is oversimplified, the linearity of the correlation between true and estimated distribution volumes is still maintained, although the linear regression becomes dependent on the input curve. These simulation results were confirmed when applying mathematical metabolite correction to the [11C]iomazenil study. Estimates of the distribution volume calculated with a measured input curve were linearly related to the estimates calculated using mathematical metabolite correction with correlation coefficients >0.990. However, the slope of the regression line displayed considerable variability among the subjects (0.33-0.95), demonstrating that absolute quantitation of the distribution volume was impaired. Mathematical metabolite correction is a feasible method and may prove useful in cases where actual metabolite data cannot be obtained. The potential for absolute quantitation seems limited, but the method allows the quantitative assessment of regional ratios of receptor measures.

Adult↗

PubMed1996

Effect of intravascular ligand binding on parameter estimates derived from tracer kinetic modelling.

The purpose of this study was to assess the effect of intravascular ligand binding on parameter estimates derived from tracer kinetic modelling. To this end intravascular ligand kinetics between the free and a bound compartment in plasma and the exchange of tracer between the capillary space and tissue were analysed using a simple compartment model. The effect of non-equilibrated intravascular compartments on parameter estimates was evaluated in a computer simulation. It was found that three kinetic situations must be distinguished. If the intravascular compartments are fully equilibrated when the ligand reaches the target organ, intravascular binding simply acts as a scale factor for the transport-related parameter K1. If the intravascular kinetics is very slow, only minimal binding will occur. In between there is a range where ongoing equilibration leads to time variability of K1. Since tracer kinetic modelling usually does not account for such time variability, the parameter estimates become biased, the degree of the bias depending on the intravascular binding kinetics. Furthermore the bias may be dependent on receptor density, meaning that model-derived receptor estimates are not linearly related to the true receptor density. It is concluded that intravascular ligand binding can severely affect parameter estimates derived from tracer kinetic modelling. Especially disturbing are effects due to ongoing intravascular equilibration following the arrival of the ligand in the target organ. These can be avoided by letting the ligand equilibrate with blood in a syringe prior to injection.

Blood Vessels↗