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Biomedical subjects

C Braun

Publications and source records attributed to C Braun.

At least 37 records · Page 2Linked to original sources

Impact of donor dopamine on immediate graft function after kidney transplantation.

Optimizing medical donor management may have a considerable impact on transplantation outcome. This study investigated the effect of donor dopamine on initial graft function in renal allograft recipients, involving 254 consecutive recipients of a cadaver kidney, aged 18-74 years, transplanted between 1990 and 2003. Immunosuppression was based on cyclosporine. Patients were grouped according to donor use of dopamine during intensive care. Delayed graft function (DGF), and serial creatinine concentrations were compared between the groups. Dopamine-treated and -untreated donors were very similar regarding hemodynamics and renal function. Delayed graft function occurred in 47/158 treated and 48/96 untreated kidneys (p = 0.001). Donor dopamine was associated with a more rapid decrease of s-creatinine, which became obvious on the first postoperative day. Of patients in the treated and untreated group, respectively, 81.9% and 65.8% reached a s-creatinine level less than 2 mg/dL during the first month (p = 0.005). Donor dopamine remained predictive of a normalized s-creatinine level [HR 1.71; 95% CI 1.22-2.41] after controlling for confounding factors by multivariate Cox regression. Donor dopamine is associated with improvements of initial graft function after kidney transplantation. The beneficial effect of dopamine is achievable without side-effects for the recipients, and correlates with superior long-term graft survival.

Adolescent↗

Trichosporon asahii infection of a dialysis PTFE arteriovenous graft.

Trichosporon species are the causative agents of superficial skin infections, such as white piedra. Immunocompromised hosts, particularly those with underlying hematological malignancy, are at risk of developing invasive infection, which usually progresses to disseminated life-threatening disease. Peritonitis caused by Trichosporon has been described in end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis. Here, we report on a Trichosporon infection of an arteriovenous graft in a patient on chronic hemodialysis. The infection was successfully treated with fluconazole and total surgical resection of the graft.

Antifungal Agents↗

The musician's brain: functional imaging of amateurs and professionals during performance and imagery.

We compared activation maps of professional and amateur violinists during actual and imagined performance of Mozart's violin concerto in G major (KV216). Execution and imagination of (left hand) fingering movements of the first 16 bars of the concerto were performed. Electromyography (EMG) feedback was used during imagery training to avoid actual movement execution and EMG recording was employed during the scanning of both executed and imagined musical performances. We observed that professional musicians generated higher EMG amplitudes during movement execution and showed focused cerebral activations in the contralateral primary sensorimotor cortex, the bilateral superior parietal lobes, and the ipsilateral anterior cerebellar hemisphere. The finding that professionals exhibited higher activity of the right primary auditory cortex during execution may reflect an increased strength of audio-motor associative connectivity. It appears that during execution of musical sequences in professionals, a higher economy of motor areas frees resources for increased connectivity between the finger sequences and auditory as well as somatosensory loops, which may account for the superior musical performance. Professionals also demonstrated more focused activation patterns during imagined musical performance. However, the auditory-motor loop was not involved during imagined performances in either musician group. It seems that the motor and auditory systems are coactivated as a consequence of musical training but only if one system (motor or auditory) becomes activated by actual movement execution or live musical auditory stimuli.

Acoustic Stimulation↗

Feature-specific electrophysiological correlates of texture segregation.

Discrimination between a figure and its surround is an important first step of pattern recognition. This discrimination usually relies, as a first step, on the detection of borders between a figure and its surround, for example based on spatial gradients in luminance, colour, or texture. There is evidence that neurones in the visual cortex are specifically activated by segregation between textures, but the relation between segregation based on different types of features such as colour, luminance, and motion is unclear. Evoked EEG potentials specific to texture segregation were investigated in 17 observers in two separate experiments and by means of functional magnetic resonance imaging in a separate study (Fahle et al., in preparation). Differences in either luminance, colour, line orientation, motion, or stereoscopic depth defined a checkerboard pattern. Patterns defined by each of these features elicited segregation-specific potentials. In contrast to earlier reports (Vision Research 37 (1997) 1409), however, we find pronounced differences between the segregation-specific potentials evoked through different features, especially regarding their peak latencies. The topographical distribution of the activity evoked reveals different polarities and partly specific locations for different stimulus features, indicating the existence of different processors for texture segregation based on different features.

Adult↗

Treatment of chronic renal allograft rejection in rats with a low-molecular-weight heparin (reviparin).

BACKGROUND: Low-molecular-weight heparin (LMWH) has been shown to prolong survival of rat cardiac allografts independently from immunosuppressive treatment. Furthermore, long-term treatment reduces the development of chronic graft vascular disease after experimental heart transplantation. The aim of the present study was to determine whether treatment with the LMWH reviparin has a beneficial effect on chronic rejection in a rat renal allograft model. METHODS: Kidneys of Fisher (F344) rats were transplanted into unilaterally nephrectomized Lewis (LEW) recipients. LEW-->LEW isografts served as controls. Animals were treated with cyclosporine (5 mg/kg/d) for the first 10 days. Nephrectomy of the remaining kidney was performed after 10 days. Allografted animals were treated either with reviparin (2 mg/kg/d subcutaneously) for 24 weeks (Allo-24), from week 12 to 24 (Allo-12), or with vehicle for 24 weeks. Proteinuria was determined at regular intervals. Kidneys were harvested after 24 weeks for histomorphological and immunohistochemical evaluation. RESULTS: No major bleeding complications were observed in reviparin-treated animals. Proteinuria was significantly reduced in allografted animals both by early as well as by late-onset treatment with reviparin. Transplant glomerulopathy was diminished in Allo-24 and in Allo-12 groups compared to vehicle-treated animals, whereas tubulointerstitial inflammation was influenced only in animals immediately treated with reviparin. Immunohistochemical studies demonstrated a marked reduction of renal monocyte and T-cell infiltration as well as expression of MHC II by treatment with reviparin. CONCLUSIONS: Treatment with the LMWH reviparin significantly improved chronic renal allograft rejection in the F344-to-LEW rat model, both after early and late start of therapy. Although the exact mechanisms of this beneficial effect remain unclear, our data offer a potential new therapeutical approach for prevention of chronic allograft nephropathy.

Animals↗

Polymorphisms of the ICAM-1 gene are associated with inflammatory bowel disease, regardless of the p-ANCA status.

The intercellular adhesion molecule-1 (ICAM-1) is of paramount importance for the initiation and propagation of various inflammatory conditions. An increased frequency of allele R241 of the ICAM-1 gene was previously described in p-ANCA-negative as compared to p-ANCA-positive ulcerative colitis and vice versa in Crohn's disease. One hundred sixteen healthy unrelated controls, 121 patients with ulcerative colitis, and 96 patients with Crohn's disease were genotyped for two polymorphisms of the ICAM-1 gene (R/G241, exon 4; and K/E469, exon 6), employing dot-blot hybridization and stratified according to their p-ANCA status. When compared with the control group the frequency of the allele R241 (P = 0.024) and the heterozygous genotype R/G241, P = 0.032) were significantly increased in ulcerative colitis, whereas the homozygous genotype G/G241 was found less frequently (P = 0.022). The heterozygous genotype K/E469 was observed less frequently (P = 0.001 and 0.037, resp.) than the homozygous genotype E/E469, which was more frequent in Crohn's disease and ulcerative colitis (P = 0.002 and 0.012, respectively). Further significant differences concerning the allele or genotype distribution were not observed. After stratification for the p-ANCA status significant differences concerning the frequencies of both the R241 and the E469 alleles were not detected when p-ANCA-positive inflammatory bowel disease and p-ANCA-negative inflammatory bowel disease were compared. Ulcerative colitis and Crohn's disease are associated with polymorphisms of the ICAM-1 gene, which might therefore represent a functional candidate gene. However, the observed associations are independent of the p-ANCA status.

Alleles↗

The distribution of mislocalizations across fingers demonstrates training-induced neuroplastic changes in somatosensory cortex.

The somatosensory system has been shown to alter its cortical activation patterns in reaction to changes in the attended sensory input to certain body parts. Whether these modifications in the functional organization of the somatosensory cortex of humans also result in perceptual changes has rarely been investigated. Here we used near-threshold tactile stimuli to the center of the fingertips to evoke mislocalizations to fingers other than the stimulated. In healthy untrained subjects, the distribution of the mislocalizations from each of the fingers was different from a distribution expected if the subjects were purely guessing the position of the stimulus. The digits next to the stimulated one receive a higher number of mislocalizations than digits further away from the stimulated digits. This decrease can be accounted for by digit-overlapping receptive fields in combination with the sequential representation of the digits in the primary somatosensory cortex. In a second experiment subjects received 20 h of simultaneous stimulation of the left thumb and little finger in the context of a perceptual task. For both hands, the distribution of mislocalization from these fingers was analyzed at the beginning and the end of the training. For the left hand, the number of assigned mislocalizations to the most distant neighbor digit (i.e., the simultaneously stimulated digit in the training) increased while the number of mislocalizations toward the direct neighboring digit decreased with the training. This change did not occur in the untrained right hand, or in the untrained subjects. We conclude that the distribution of mislocalization to fingers other than the stimulated can be used to investigate perceptual changes paralleling training-induced modifications in the activation patterns of the somatosensory cortex.

Adult↗

The Kapandji technique for fixation of distal radius fractures--a biomechanical comparison of primary stability.

The goal of this study was to compare Kapandji-K-wiring and established K-wiring techniques of the distal radius fracture for primary stability in a biomechanical model: dorsal K-wiring according to Kapandji using different angles of the K-wire, parallel and diagonal alignment of the K-wires. A new testing system which uses a synthetic material enabled us to carry out the cantilever bending test. By application of a lower load, the Kapandji procedure shows a higher reactive torque and stiffness. A higher reaction force of the other techniques, especially of the parallel wiring, are only observable under high-grade bending stress. Application of the Kapandji procedure with K-wires at a smaller angle to the axis of the radius results in the highest primary stability of the procedures investigated in the essential range of initial deformation.

Biomechanical Phenomena↗

Endovascular stent-graft placement versus conventional open surgery in infrarenal aortic aneurysm: a prospective study on acute phase response and clinical outcome.

BACKGROUND: For the treatment of aortic aneurysm, stent-graft implantation is an alternative method to open surgery. There is no study comparing both methods with regard to endotoxaemia, the acute phase cascade, and clinical outcome. METHODS: In this prospective study, we enrolled 40 patients (34 males, 6 females; mean age 72.1+/-7.5 [58-92] years) with infrarenal abdominal aortic aneurysm who underwent aortic surgery. Comparable groups of patients were treated with open (n=20) or endovascular (n=20) stent-graft implantation. To characterize the inflammatory response, plasma levels of endotoxin, endotoxin-neutralizing capacity (ENC), interleukin-6 (IL-6), C-reactive protein (CRP), and white blood cell count were determined. In all patients, measurements were performed on admission, skin suture, 4 h and from the first to fifth postoperative day. As parameters for the clinical outcome, we assessed daily temperature, lung function, pain, duration of postoperative hospital stay, and morbidity. Wilcoxon rank test was used for statistical analysis. RESULTS: In both groups, a significant increase of endotoxin plasma levels and a decrease of ENC was found already after skin incision. IL-6 levels peaked 4 h postoperatively in both groups, whereas CRP rose at the first postoperative day, reaching a maximum at day 2. Conventionally operated patients had significantly higher plasma levels of endotoxin, IL-6, and CRP and lower ENC during and after surgery than patients with stent-graft implantation. Moreover, patients with endovascular stent grafting had significant less postoperative pain, less restriction of total vital capacity, a shorter hospital stay, and a lower morbidity. CONCLUSIONS: Endovascular stent grafting of infrarenal aortic aneurysm seems to be superior not only in terms of the inflammatory response but also in overall clinical outcome.

Acute-Phase Reaction↗

Hyperexcitatory activity in visual cortex in homonymous hemianopia after stroke.

OBJECTIVES: Damage to and destruction of neural afferents result in a disruption of sensory input, which causes reduced activity in the corresponding cortical areas. Conversely, there is also evidence that lesions in the sensory pathway induce changes in the intracortical connectivity resulting in augmented cortical activity due to disinhibition. As disinhibition is assumed to be involved in the reconfiguration of neural networks, its appearance after brain lesions might be relevant for the restitution of impaired brain functions. METHODS: The effects of lesions in the visual pathway on the activity in visual cortex were studied using magnetoencephalography. In order to compare the neural activity affected by the lesion with the activity associated with intact visual processing, only patients with unilateral, post-chiasmatic lesions resulting in homonymous hemianopia were examined. RESULTS: Stimulation within the scotoma resulted in reduced magnetic activity compared to the stimulation of the intact hemifield. Increased activity was observed when the border region of the scotoma was stimulated. CONCLUSIONS: It is concluded that the magnetic hyperactivity reflects cortical disinhibition induced by lesions in the visual system. Furthermore, the possible role of cortical disinhibition as a basis for cortical reorganization and as a precondition for the recovery of impaired visual functions is discussed.

Hemianopsia↗

Dynamic organization of the somatosensory cortex induced by motor activity.

Intensive and long-lasting experience of altered sensory input induces permanent changes in the functional organization of the somatosensory cortex. In addition, an increasing body of evidence suggests the existence of dynamic, short-term and task-dependent adaptation of representational maps within somatosensory cortex. It is hypothesized that somatosensory maps can, not only, be acquired within a short period of time, but might also be set up during periods of training related to specific tasks and subsequently activated dynamically upon performance of that particular task. In order to test this hypothesis we studied the functional organization of somatosensory cortex for a heavily overlearned and frequently performed task for which no new acquisition of a sensory map had to be assumed. To this end, the functional organization of somatosensory cortex for handwriting was compared with the organization during rest in healthy humans. Functional organization of the somatosensory cortex was assessed using non-invasive, neuromagnetic source imaging based on tactile stimulation of the thumb (D1) and little finger (D5) during writing and rest. In different blocks, subjects wrote with their right, dominant and their left hand, respectively. During writing, D1 and D5 of the writing hand were stimulated. To test the reliability of our results all measurements were repeated after 1 week. It was found that amplitudes of somatosensory evoked magnetic fields with latencies of 45 ms were reduced during writing compared with rest. This finding is in accordance with the sensorimotor gating effect. Using source localization we could show that cortical representations of D1 and D5 are more distant during writing with either hand compared with rest. Our data suggest that somatosensory cortical maps undergo rapid modulation depending on task-specific involvement of sensory processing in daily-life overlearned movements. As it is unlikely that a new sensory map is always acquired when a frequently used task such as writing is performed, we suggest that somatosensory cortex switches between different, concurrently pre-existing maps depending on actual requirements. Task-dependent activation of pre-existing maps might be a powerful mechanism to optimize stimulus processing.

Adult↗

Therapeutic administration of an endothelin-A receptor antagonist after acute ischemic renal failure dose-dependently improves recovery of renal function.

Endothelin (ET) is known to reduce glomerular filtration rate and renal blood flow and is a possible mediator of acute renal failure (ARF). We recently demonstrated that the administration of a very high dose of the ET(A)-receptor antagonist LU 135252 (LU) accelerates recovery from postischemic acute renal failure by an improvement of renal perfusion in a rat model. The aim of this study was to investigate whether this effect of LU is dose dependent. ARF was induced in rats by clamping both renal arteries. Serum creatinine was measured and endogenous creatinine clearance and fractional sodium excretion were calculated up to 4 days after acute ischemia. Rats were treated either with the selective ET(A)-receptor antagonist LU or with vehicle only after reperfusion. LU in doses of 0.5, 1, or 5 mg/kg per day was infused via a femoral vein using an osmotic minipump. Serum creatinine was increased approximately eightfold after induction of ARF. Creatinine clearance decreased from 4.35 +/- 0.26 ml/min before acute renal failure to 0.15 +/- 0.02, 0.54 +/- 0.1, and 1.49 +/- 0.19 ml/min on days 1, 2, and 4 after ischemia (p < 0.05). Fractional sodium excretion increased from baseline 0.77 +/- 0.05% to 7.5 +/- 1.21 % on day 1 and 8.53 +/- 1.34% on day 2 (p < 0.05). Treatment with LU improved kidney function dose relatedly. There was no significant change in creatinine clearance, but compared with controls, with doses of 0.5 mg/kg per day and 1 mg/kg per day (0.28 +/- 0.1, 0.88 +/- 0.22, and 1.93 +/- 0.24 ml/min on days 1, 2, and 4), we noted a significant increase under 5 mg/kg per day (day 1: 0.62 +/- 0.17 ml/min; day 2: 1.38 +/- 0.26 ml/min; and day 4: 2.45 +/- 0.21 ml/min; p < 0.05). Fractional sodium excretion decreased dose-relatedly to a maximally 2.48 +/- 0.58% on day 1 and 2.25 +/- 0.71 % on day 2 after treatment with the highest dose when compared with untreated control rats (p < 0.05). Our data support the hypothesis that ET plays a major role in ARF. It can be concluded from these results that recovery from ischemic ARF is significantly and dose-dependently enhanced by treatment with a selective ET(A)-receptor antagonist.

Acute Kidney Injury↗

Activity patterns of human somatosensory cortex adapt dynamically to stimulus properties.

Long-term synchronous tactile stimulation of two sites of the body results in integrated, overlapping cortical representations whereas asynchronous stimulation leads to segregated representations. To investigate the cortical capacity to adapt dynamically to stimulation properties 22 subjects were stimulated at digits 1, 3 and 5 of both hands in either random or fixed order. Changes in the functional organization of the somatosensory cortex were inferred by neuromagnetic source analysis based on somatosensory evoked magnetic fields. Compared to the stimulation in random sequence, the stimulation in fixed order revealed a reduction in distance between the cortical representation of D1 and D3. We conclude that the pattern of activation in the somatosensory cortex adapts dynamically to the spatio-temporal characteristics of the stimuli.

Adult↗

Subsite mapping of the human pancreatic alpha-amylase active site through structural, kinetic, and mutagenesis techniques.

We report a multifaceted study of the active site region of human pancreatic alpha-amylase. Through a series of novel kinetic analyses using malto-oligosaccharides and malto-oligosaccharyl fluorides, an overall cleavage action pattern for this enzyme has been developed. The preferred binding/cleavage mode occurs when a maltose residue serves as the leaving group (aglycone sites +1 and +2) and there are three sugars in the glycon (-1, -2, -3) sites. Overall it appears that five binding subsites span the active site, although an additional glycon subsite appears to be a significant factor in the binding of longer substrates. Kinetic parameters for the cleavage of substrates modified at the 2 and 4' ' positions also highlight the importance of these hydroxyl groups for catalysis and identify the rate-determining step. Further kinetic and structural studies pinpoint Asp197 as being the likely nucleophile in catalysis, with substitution of this residue leading to an approximately 10(6)-fold drop in catalytic activity. Structural studies show that the original pseudo-tetrasaccharide structure of acarbose is modified upon binding, presumably through a series of hydrolysis and transglycosylation reactions. The end result is a pseudo-pentasaccharide moiety that spans the active site region with its N-linked "glycosidic" bond positioned at the normal site of cleavage. Interestingly, the side chains of Glu233 and Asp300, along with a water molecule, are aligned about the inhibitor N-linked glycosidic bond in a manner suggesting that these might act individually or collectively in the role of acid/base catalyst in the reaction mechanism. Indeed, kinetic analyses show that substitution of the side chains of either Glu233 or Asp300 leads to as much as a approximately 10(3)-fold decrease in catalytic activity. Structural analyses of the Asp300Asn variant of human pancreatic alpha-amylase and its complex with acarbose clearly demonstrate the importance of Asp300 to the mode of inhibitor binding.

Acarbose↗

Differential activation in somatosensory cortex for different discrimination tasks.

Maps of the body surface in somatosensory cortex have been shown to be highly plastic, altering their configuration in response to changes in use of body parts. The current study investigated alterations in the functional organization of the human somatosensory cortex resulting from massed practice. Over a period of 4 weeks, subjects were given synchronous tactile stimulation of thumb (D1) and little finger (D5) for 1 hr/d. They had to identify the orientation of the stimuli. Neuroelectric source localization based on high-resolution EEG revealed that, when subjects received passive tactile stimulation of D1 or D5, the representations of the fingers in primary somatosensory cortex were closer together after training than before. There was also an apparently correlative tendency to anomalously mislocalize near-threshold tactile stimuli equally to the distant finger costimulated during training rather than preferentially to the finger nearest to the finger stimulated in a post-training test. However, when the stimulus discrimination had to be made, neuroelectric source imaging revealed that the digital representations of D1 and D5 were further apart after training than before. Thus, the same series of prolonged repetitive stimulations produced two different opposite effects on the spatial relationship of the cortical representations of the digits, suggesting that differential activation in the same region of somatosensory cortex is specific to different tasks.

Adult↗

An immediate, allergic skin reaction to aprotinin after reexposure to fibrin sealant.

BACKGROUND: The safety of fibrin tissue adhesives has been a concern since they entered wide clinical application. Most commercially available kits contain the proteolytic inhibitor, aprotinin, to stabilize the fibrin clot. A bovine protein, this substance has an allergenic potency. CASE REPORT: This case report presents a patient who had a generalized allergic skin reaction, probably triggered by aprotinin upon reexposure to fibrin sealant injected subgaleally to achieve closure of a liquor fistula after neurosurgical treatment. The serologic investigation revealed aprotinin-specific IgE and IgG. From 1990 through 1998, reports of five allergic reactions following 1 million exposures to fibrin sealant were made to the manufacturer. The clinical relevance of allergic reactions to aprotinin contained in fibrin sealants and measures to avoid them are discussed. CONCLUSION: These hypersensitivity reactions are extremely rare (incidence, 0.5/100,000 for all reactions and 0.3/100,000 for serious reactions), but they must be kept in mind as possible adverse events after repeated applications of fibrin sealants within a few weeks.

Antibodies, Anti-Idiotypic↗