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Biomedical subjects

V Braun

Publications and source records attributed to V Braun.

At least 19 recordsLinked to original sources

[DNA sperm methylation in assisted reproductive techniques].

In the last few years, many tests were developed to study the fertilizing properties of the spermatozoa. However none of them was useful to obtain a prognostic factor. Indeed, the integrity of the spermatic DNA is also necessary to a successful fertilization for obtaining a pregnancy. DNA integrity could be evaluated by the measurement of the level of DNA methylation. Indeed, in the mammals, the methylation of the ADN is involved in diverse processes amongst them the regulation of the genome expression during the embryonic development. The objective of this study is to evaluate the impact of the level of methylation of the spermatic DNA in the success of in vitro fertilization (IVF), in terms of rate of fertilization, quality of the embryos and rate of pregnancy. The immunostaining of the 5-methylecytosine, then the quantification by image analysis or with flow cytometry, allowed an objective evaluation of the level of total methylation of spermatic DNA. Our data show that the level of DNA methylation influences neither the fertilization rate nor the embryos quality. On the other hand, the rate of pregnancy is decreased if the total level of DNA methylation is lower than a threshold value. The level of spermatic DNA methylation represents a new parameter of spermatic maturation.

5-Methylcytosine↗

Brain tumour surgery in the vicinity of short-term memory representation--results of neuronavigation using fMRI images.

OBJECTIVE: Functional information concerning the surrounding brain is mandatory for a good clinical outcome in brain tumour surgery. The value of fMRI to detect the motorcortex and Broca's area is widely accepted today. If an appropriate paradigm is used, short-term memory areas can be visualized as well. Obviously this information must be integrated into cranial neuronavigation for an appropriate intra-operative use. We report our first experiences with the direct integration of short-term memory fMRI into cranial neuronavigation. METHOD: From January 2001 to March 2002 14 patients were operated on for intracranial tumours with short-term memory fMRI imaging, using the "two-back-paradigm". Both pre- and postoperatively, the short-term memory of all patients was tested additionally by a standardized test battery including 16 different verbal and visuo-spatial items. RESULTS: In all 14 patients the general level of working memory capacity was preserved after surgery. The visuo-spatial performance was kept unchanged or deteriorated slightly, the alertness slightly worsened as well, but we found an improvement in verbal test items. CONCLUSION: The two-back paradigm is able to visualize verbal memory tasks in fMRI. For visuo-spatial items, a new paradigm has to be designed. In contrast to deep seated brain lesions, focal cortical impairments do not lead to obvious and serious memory deficits. Therefore, the aim of gross total tumour removal has to be balanced against the aim of preservation of short-term memory fields. Nevertheless, the knowledge of the localization of cortical short-term memory fields may combine both aims during navigated brain tumour surgery, thus preserving the patient with a better quality of life.

Adult↗

Influence of global sperm DNA methylation on IVF results.

BACKGROUND: In cases of male infertility, routine analysis for sperm characteristics is a poor predictive factor for the segmentation rate and embryo development in assisted reproductive technologies. It is assumed that epigenetic factors could have an influence on the embryo's quality. The aim of this work was to determine the relationship between sperm DNA methylation level and fertilization and pregnancy rates according to the assisted reproduction technique performed. METHODS: A prospective study was undertaken. Ejaculates were obtained from men (n = 63) undergoing an assisted reproduction procedure. 5-Methylcytosine was immunostained with a polyclonal antibody and revealed by fluorescein isothiocyanate. The DNA methylation level was then quantified by flow cytometry. RESULTS: Sixty-three conventional IVF cycles were performed, 760 oocytes were retrieved, an average of 8.1 +/- 4.8 embryos was obtained, and 2.4 embryos were transferred. Neither the fertilization rate nor the rate of good quality embryos was correlated with the DNA methylation level (r = -0.1 and r = -0.08 respectively; not significant). When sperm DNA methylation was >555 arbitrary units, the pregnancy rate was 33.3% compared with 8.3% in the lower (<555) group (P<0.05). CONCLUSION: DNA methylation level in human sperm could represent a new approach to study the ability of sperm to lead to pregnancy in an assisted reproduction procedure, especially when sperm samples with normal characteristics are used.

5-Methylcytosine↗

[Management of iatrogenic lesions of the spinal accessory nerve].

Lesions of the spinal accessory nerve are usually iatrogenic, especially after lymph node extirpation on the neck. Between 1994 and 2003, 31 patients were operated on in the Neurosurgical Department of the University of Ulm for iatrogenic lesions of the XIth cranial nerve. Of 31 patients, 22 had undergone a previous lymph node extirpation, 2 had been injured during a selective peripheral denervation for spasmodic torticollis, and the other 7 patients by different causes. The neurosurgical intervention was performed 0-19 months after trauma (mean 7.2 months). All patients showed paresis/atrophy of the trapezius muscle, and the abduction of the shoulder was markedly reduced. Additional neck and/or shoulder pain was present in 29 of 31 cases. In seven cases, the nerve was compressed by scar tissue and subsequently treated by external neurolysis. Ten patients underwent an end-to-end anastomosis; autologous sural nerve grafting was necessary in 13 cases. After a mean follow-up of 12.6 months, 7 of 31 patients completely recovered. Of 31 patients, 19 experienced partial relief of pain and weakness. Only five patients remained unchanged. The clinical findings after autologous nerve grafting, end-to-end reconstruction, or external neurolysis did not show any significant differences. Microsurgical reconstruction of iatrogenic injury of the spinal accessory nerve is very promising if the interval between trauma and surgical revision is less than 6 months. Up to 12 months, partial recovery can be achieved. Outcome after longer delay is unsatisfactory.

Accessory Nerve↗

Coincidental deficiency of the posterior arch of the atlas and thalassaemia minor: possible pitfalls in a trauma victim.

Congenital abnormalities of the cervical spine are rare findings in trauma victims. Deficiency of the posterior arch of the atlas and coincidental thalassaemia minor are even more unusual. This case report is about a young female trauma victim with both abnormalities, a combination that has previously not been described in literature. The classification, as proposed by Currarino et al in 1994, and the importance of being aware of these abnormalities are discussed.

Adolescent↗

Lipomas of the internal auditory canal--report of two cases and review of the literature.

OBJECTIVE: Lipomas of the internal auditory canal are extremely rare. So far, only 21 cases have been described in the literature. We present here two of our own cases and review the literature to date with special emphasis on the diagnostic and therapeutic options. METHOD: During the last seven years two lipomas of the internal auditory canal were surgically treated in our department. Despite native and gadolinium-enhanced MRI and a thin-sliced temporal bone CT scan they were misdiagnosed as intracanalicular acoustic neurinomas. RESULTS: Total tumour removal could be achieved, the facial nerve function was conserved, but both patients were rendered functionally deaf after surgery. CONCLUSION: Lipomas' radiological behaviour may mimic acoustic neurinomas; without fat-suppressed T(1)-weighted images they are often preoperatively misdiagnosed as acoustic neurinomas. Although the postoperative morbidity with respect to cochlear and facial nerve function is much higher than in small acoustic schwannomas, early surgery may be justified, because complete removal is only possible in this stage. No reliable data are available concerning the natural history of this kind of lesion.

Adult↗

ALES: cell lineage analysis and mapping of developmental events.

MOTIVATION: Animals build their bodies by altering the fates of cells. The way in which they do so is reflected in the topology of cell lineages and the fates of terminal cells. Cell lineages should, therefore, contain information about the molecular events that determined them. Here we introduce new tools for visualizing, manipulating, and extracting the information contained in cell lineages. Our tools enable us to analyze very large cell lineages, where previously analyses have only been carried out on cell lineages no larger than a few dozen cells. RESULTS: Ales (A Lineage Evaluation System) allows the display, evaluation and comparison of cell lineages with the aim of identifying molecular and cellular events underlying development. Ales introduces a series of algorithms that locate putative developmental events. The distribution of these predicted events can then be compared to gene expression patterns or other cellular characteristics. In addition, artificial lineages can be generated, or existing lineages modified, according to a range of models, in order to test hypotheses about lineage evolution. AVAILABILITY: The program can run on any operating system with a compliant Java 2 environment. Ales is free for academic use and can be downloaded from http://mbi.dkfz-heidelberg.de/mbi/research/cellsim/ales.

Algorithms↗

Two-step purification of the outer membrane transporter and activator protein ShlB from Escherichia coli using internally His6-tagged constructs.

ShlB from Serratia marcescens was isolated and purified from a porin-deficient Escherichia coli BL21 strain using a combination of detergent extraction, affinity and ion-exchange chromatography. An internal histidine affinity tag was introduced that did not interfere with activity. At each stage of the purification scheme biological activity of the ShlB protein was assessed. Using this scheme, several His(6)-tagged mutants of ShlB were purified to electrophoretic homogeneity.

Affinity Labels↗

[Costs of ambulant care for patients with inflammatory bowel disease in general practice].

BACKGROUND: Outpatient care managed by general practitioners plays an important role in diagnostic and treatment of inflammatory bowel diseases (IBD). The chronic recurrent course often requires intensive and costly medical care. OBJECTIVE: To measure the costs of outpatient care for patients with IBD provided by general practitioners (GPs). MATERIAL AND METHODS: The analysis is based on an electronic data base implemented in 100 general practices in different parts of Germany. 191 patients with altogether 705 consultations over a period of one year were included in the analysis. Costs of care were measured using German fee schedules for health care delivery and market prices for drugs. RESULTS: In a 12-months-period the mean number GP-contacts was 3.6. Mean costs were 23.61 euro; per visit and annual costs were 87.15 euro; per patient. Pharmacotherapy was used by 147 patients (77%) and caused costs of 613.40 euro; per year, with 64% due to the use of salicylates. 66 patients (35%) also had diagnostic services provided from specialists, 7 patients (4%) required psychotherapeutic care. CONCLUSION: The presented study is the first to analyse in detail the costs for medical care of IBD in general practices in Germany. Results can be used in economic assessment of the disease and in cost-effectiveness-analyses of intervention strategies. They may support treatment guidelines and treatment decisions from an economic point of view.

Adolescent↗

Cranial neuronavigation with direct integration of (11)C methionine positron emission tomography (PET) data -- results of a pilot study in 32 surgical cases.

BACKGROUND: MRI detects small intracranial lesions, but has difficulties in differentiating between tumour, gliosis and edema. (11)C methionine-PET may help to overcome this problem. For its appropriate intra-operative use, it must be integrated into neuronavigation. We present the results of our pilot study with this method. METHOD: 32 patients with 34 intracranial lesions detected by MRI underwent additional (11)C methionine-PET, because the pathophysiological behaviour or the tumour delineation was unclear. All lesions were treated surgically. In 25 patients PET data could be integrated directly into cranial neuronavigation. FINDINGS: (11)C methionine uptake was observed in 27/34 lesions, 26 of them were tumours: 14 malignant and 7 benign gliomas, 3 gliomas without further histological typing, one Ewing sarcoma and one non-Hodgkin lymphoma. Only one (11)C methionine positive lesion was non-tumourous: it was staged as post-irradiation necrosis in a patient operated on for a malignant glioma. 3/7 (11)C-methionine negative lesions were classified as gliosis (n=2) and M. Whipple (n=1), but 4/7 were tumours: 2 astrocytomas WHO(degrees)II, 1 DNT and one astrocytoma WHO(degrees)III. The sensitivity of (11)C methionine-PET was 87%, the specificity 75%, the positive predictive value 96% and the negative predictive value 43%. In all tumourous cases with positive tracer uptake the borderline area of the tumour was better defined by (11)C methionine-PET than by MRI. INTERPRETATION: A positive (11)C methionine-PET is highly suspicious of a tumour, a negative one does not exclude it. (11)C methionine-PET seems to be more sensitive than MRI for differentiating between tumour and edema or gliosis. Simultaneous integration MRI and (11)C methionine-PET into cranial neuronavigation can facilitate cross total tumour removal in glioma surgery.

Brain Edema↗

Urinary infection stones.

Infection stones make up approximately 15% of urinary stone diseases and are thus an important group. These stones are composed of struvite and/or carbonate apatite. The basic precondition for the formation of infection stones is a urease positive urinary tract infection. Urease is necessary to split urea to ammonia and CO(2). As a result, ammonia ions can form and at the same time alkaline urine develops, both being preconditions for the formation of struvite and carbonate apatite crystals. When these crystals deposit themselves infection stones form. If these infections are not treated and the stones are not removed, the kidney will be damaged. For stone removal modern methods are available, e.g. ESWL and/or instrumental urinary stone removal. Here especially less invasive methods are preferable. Any treatment must be adjusted to the patient individually. Patients should be examined frequently for recurrent urinary tract infections and stone recurrences and, newly arising infections must be resolutely treated. Good therapy and prophylaxis are possible with present-day treatment modalities.

Anti-Bacterial Agents↗

Variant toxin B and a functional toxin A produced by Clostridium difficile C34.

A particular property of Clostridium difficile strain C34 is an insertion of approximately 2 kb in the tcdA-C34 gene that does not hinder expression of a fully active TcdA-C34 molecule. Intoxication with TcdA-C34 induced an arborized appearance in eukaryotic cells (D-type cytopathic effect); intoxication with TcdB-C34 induced a spindle-like appearance of cells (S-type cytopathic effect). Inactivation of GTPases with purified toxins revealed that Rho, Rac, Cdc42, and Rap are substrates of TcdA-C34. The variant cytotoxin TcdB-C34 inactivated Rho, Rac, Cdc42, Rap, Ral, and R-Ras. Hence, this is the first 'S-type' cytotoxin which inactivates both Rho and R-Ras, and is coexpressed with a 'D-type' enterotoxin. Our results support the hypothesis that R-Ras is a key GTPase related to the S-type cytopathic effect and suggest that induction of a S-type cytopathic effect dominates induction of the D-type cytopathic effect.

Animals↗

In vivo experiences with frameless stereotactically guided screw placement in the spine--results from 75 consecutive cases.

Whereas cranial neuronavigation is widely accepted as a helpful tool, larger series of the in vivo application of spinal neuronavigation do not exist. In the following we report our 4-year experience with spinal navigation in 75 consecutive cases for dorsal transpedicular screw placement. Seventy-five patients were planned for operation employing anatomical reference points defined on a 2-mm high resolution CT. We used single vertebra registration and surface matching. With the above methods, the mean registration deviation ranged from 0.18 mm (cervical spine) to 0.31 mm (lumbar spine). All our screws in the upper cervical spine were navigated correctly (17 patients), thus improving markedly the surgical outcome. The results were not as promising in the lumbar area. In only 84% was navigation reliable. The reason was the lack of a practicable tracking tool. Spinal neuronavigation based on anatomical reference points is able to improve the results in transpedicular screwing, especially in the cervical spine. The lack of a practicable tracking tool still hinders its use in routine clinical application.

Bone Screws↗

Case reports of symptomatic metastases in four patients with primary intracranial gliomas.

Four patients with primary intracranial high-grade gliomas are reported. Three of them developed spinal symptoms and signs generated by spinal metastases a few months after first diagnosis, the last patient developed an extraspinal metastasis in cervical lymph nodes. The spinal metastasis of a 30 years old patient was located intradurally at L5/S1, in the second patient at level L3, the third patient presented with multiple metastases in the cervical, thoracic and lumbar spine. Previously reported cases are reviewed, are discussed in the light of our own observations and analysed for the various therapeutic options.

Adult↗

Active transport of an antibiotic rifamycin derivative by the outer-membrane protein FhuA.

BACKGROUND: FhuA, an integral membrane protein of Escherichia coli, actively transports ferrichrome and the structurally related antibiotic albomycin across the outer membrane. The transport is coupled to the proton motive force, which energizes FhuA through the inner-membrane protein TonB. FhuA also transports the semisynthetic rifamycin derivative CGP 4832, although the chemical structure of this antibiotic differs markedly from that of ferric hydroxamates. RESULTS: X-ray crystallography revealed that rifamycin CGP 4832 occupies the same ligand binding site as ferrichrome and albomycin, thus demonstrating a surprising lack of selectivity. However, the binding of rifamycin CGP 4832 is deviant from the complexes of FhuA with hydroxamate-type ligands in that it does not result in the unwinding of the switch helix but only in its destabilization, as reflected by increased B factors. Unwinding of the switch helix is proposed to be required for efficient binding of TonB to FhuA and for coupling the proton motive force of the cytoplasmic membrane with energy-dependent ligand transport. The transport data from cells expressing mutant FhuA proteins indicated conserved structural and mechanistic requirements for the transport of both types of compounds. CONCLUSIONS: We conclude that the binding of rifamycin CGP 4832 destabilizes the switch helix and promotes the formation of a transport-competent FhuA-TonB complex, albeit with lower efficiency than ferrichrome. Active transport of this rifamycin derivative explains the 200-fold increase in potency as compared to rifamycin, which is not a FhuA-specific ligand and permeates across the cell envelope by passive diffusion only.

Allosteric Site↗

Iron uptake mechanisms and their regulation in pathogenic bacteria.

In the human body iron is present in growth-limiting amounts for bacteria. For this reason intricate iron transport and iron regulatory systems evolved in bacteria to guarantee a sufficient iron supply. The few principal mechanisms that underly the large variety of iron supply systems will be presented, as well as cases, in which defined iron supply systems are related to virulence.

Bacteria↗

Effect of volatile anesthetics on the force-frequency relation in human ventricular myocardium: the role of the sarcoplasmic reticulum calcium-release channel.

BACKGROUND: In human ventricular myocardium, contractile force increases at higher stimulation frequencies (positive force-frequency relation). In failing hearts, the force-frequency relation (FFR) is negative. Data on the effect of volatile anesthetics on FFR are very limited. METHODS: The authors obtained left ventricular tissue from 18 explanted hearts from patients undergoing cardiac transplantation and tissue of 8 organ donors. The negative inotropic effect of halothane, isoflurane, and sevoflurane on isometric force of contraction of isolated muscle preparations at a stimulation frequency of 1 and 3 Hz and the effect of each anesthetic on the FFR were studied. Ryanodine and verapamil were studied for comparison. In addition, the effect of the anesthetics on Ca(2+)-dependent (3)H-ryanodine binding was investigated. RESULTS: In nonfailing myocardium, halothane was the strongest negative inotropic compound, and the positive FFR was not affected by either drug. In failing myocardium, halothane also showed the strongest negative inotropic effect, but the positive shape of FFR was restored by halothane and ryanodine. In contrast, isoflurane, sevoflurane, and verapamil did not change FFR. Only halothane shifted the Ca(2+)-dependent (3)H-ryanodine binding curve toward lower Ca(2+) concentrations. CONCLUSION: In nonfailing human myocardium, none of the anesthetics affect FFR, but halothane is the strongest negative inotropic compound. In failing myocardium, halothane, but not isoflurane or sevoflurane, restores the positive shape of FFR. Both the more pronounced negative inotropic effect of halothane and the restoration of the positive shape of FFR in failing myocardium in the presence of halothane can be explained by its interaction with the myocardial sarcoplasmic reticulum calcium-release channel.

Anesthetics, Inhalation↗