Identification of less-irradiating tube angulations in invasive cardiology

OBJECTIVES: We sought to identify tube angulations in invasive cardiology, which promise minimal radiation exposure to patients and operators. BACKGROUND: Radiation exposure in invasive cardiology is high. METHODS: We mapped the fluoroscopic dose-area product per second (DAP/s), applied to an anthropomorphic Alderson-Rando phantom and, in absence of radiation protection devices, the mean personal dose in the operator's position in 10 degrees steps from the 100 degrees right anterior oblique (RAO) to the 100 degrees left anterior oblique (LAO) projection, as well as for all geometrically feasible craniocaudal tube angulations. RESULTS: For our specific setting conditions RAO 20 degrees /0 degrees tube angulation generated the lowest DAP/s and operator's personal dose. The mean patient DAP/s and operator personal dose for all postero-anterior (PA) projections, cranialized and caudalized together, rose significantly: 3.7 and 10.6 times the PA 0 degrees baseline values toward LAO 100 degrees and 3.7 and 2.4 times toward RAO 100 degrees , respectively. Patient and operator values for all PA projections, angulated to the right and left, increased approximately 2.5 times toward 30 degrees craniocaudal angulations. Caudal PA 0 degrees /30 degrees - angulation instead of caudal LAO 60 degrees /20 degrees - angulation for the left coronary main stem and cranial PA 0 degrees /30 degrees + view in place of cranial LAO 60 degrees /20 degrees + view for the left anterior descending coronary artery bifurcation enable 2.6-fold dose reductions to the patient and eight- and five-fold dose reductions to the operator, respectively. CONCLUSIONS: The PA views and RAO views >or=40 degrees , heretofore unconventional in clinical routine, should be favored over steep LAO projections >or=40 degrees whenever possible. Tube angulations that are radiation intensive to the patient exponentially increase the operator's radiation risk.     

Glutaredoxin regulates vascular development by reversible glutathionylation of sirtuin 1

Embryonic development depends on complex and precisely orchestrated signaling pathways including specific reduction/oxidation cascades. Oxidoreductases of the thioredoxin family are key players conveying redox signals through reversible posttranslational modifications of protein thiols. The importance of this protein family during embryogenesis has recently been exemplified for glutaredoxin 2, a vertebrate-specific glutathione–disulfide oxidoreductase with a critical role for embryonic brain development. Here, we discovered an essential function of glutaredoxin 2 during vascular development. Confocal microscopy and time-lapse studies based on two-photon microscopy revealed that morpholino-based knockdown of glutaredoxin 2 in zebrafish, a model organism to study vertebrate embryogenesis, resulted in a delayed and disordered blood vessel network. We were able to show that formation of a functional vascular system requires glutaredoxin 2-dependent reversible S-glutathionylation of the NAD⁺-dependent protein deacetylase sirtuin 1. Using mass spectrometry, we identified a cysteine residue in the conserved catalytic region of sirtuin 1 as target for glutaredoxin 2-specific deglutathionylation. Thereby, glutaredoxin 2-mediated redox regulation controls enzymatic activity of sirtuin 1, a mechanism we found to be conserved between zebrafish and humans. These results link S-glutathionylation to vertebrate development and successful embryonic angiogenesis.Embryonic development is a complex interplay between proliferation, differentiation, and apoptosis. Many signaling pathways are involved in these cellular processes, and the requirement of stringent control is obvious. The general importance of redox regulation and signaling in almost all aspects of cellular function is increasingly recognized (1), but only a limited number of specific and reversible redox signals affecting biological processes have been identified so far. Global redox signals, e.g., changes in the cellular redox state, are often transformed into specific signals by posttranslational modifications of protein cysteinyl side chains. Protein thiols can undergo a variety of modifications, disulfide formation, S-glutathionylation, or S-nitrosylation (2). Although many proteins expose cysteines (Cys) on their surface, only a few of the available thiols are targets for redox modifications, indicating that conveyance of redox signals depends on enzyme catalyzed reactions. The required enzymes are members of the thioredoxin family of proteins. Glutaredoxins (Grxs) are oxidoreductases belonging to this protein family and key enzymes controlling the redox status of protein thiols (3). This protein group can be subdivided into dithiol Grxs with a Cys-X-X-Cys active site motive and monothiol Grxs with a Cys-X-X-Ser active site motif. The catalytic activity of the latter is still elusive. Dithiol Grxs reduce disulfides via the dithiol mechanism using both cysteines of the active site motif. In addition, via the monothiol mechanism, dithiol Grxs can reduce protein–glutathione mixed disulfides (deglutathionylation) for which they require solely the N-terminal active site cysteine (4, 5). After reducing their substrates, oxidized Grx gets recycled by glutathione (GSH), which in turn is reduced through glutathione reductase with NADPH as final electron donor (4). Because Grxs are among the few known enzymes to be able to (de-) glutathionylate proteins, they are likely to be the main regulators for redox signaling through S-glutathionylation (6, 7).Two conserved additional cysteine residues characterize Grx2 as a vertebrate-specific enzyme (8, 9). Human Grx2 is expressed in three different isoforms located in mitochondria (Grx2a) and cytosol/nucleus (Grx2b and Grx2c) (10). Zebrafish Grx2 is the closest homolog of hGrx2c and seems to be mainly localized in the cytosol (9). Recently, we showed that Grx2 is indispensable for embryonic brain development (9). In zebrafish and human cells we demonstrated that Grx2 is crucial for neuronal survival and the formation of the axonal scaffold during embryonic development of the brain via reduction of a disulfide formed within collapsin response mediator protein 2 (CRMP2), the effector protein of semaphorin 3A (Sema3A) signaling. Because many signaling systems wiring brain and vasculature are closely related (11), and the importance of Grxs and redox signaling for maintenance of cardiovascular function has previously been demonstrated (12, 13), we sought to analyze the role of Grx2 for vascular development.Here, we describe an essential function of Grx2 for vascular development. The presented data based on a combination of biochemical and imaging tools as well as zebrafish as an accepted model organism suggest that successful embryonic angiogenesis depends on the redox modification of a single-cysteine residue.     

Noradrenergic stimulation and motor performance: Differential effects of reboxetine on movement kinematics and visuomotor abilities in healthy human subjects

Evidence from studies in both animals and humans suggests that pharmacological stimulation of the noradrenergic system may modulate cortical excitability. However, the influence of such a modulation on the motor system remains unclear. We here explored the effects of noradrenergic stimulation on different motor tasks with increasing complexity and sensorimotor demands. Healthy human subjects received either reboxetine - a selective noradrenaline reuptake inhibitor - or placebo in a double-blind within-subject design. The analysis of movement kinematics revealed differential effects of RBX on subjects’ motor performance. While isolated stereotypic finger movements and simple reach-to-grasp movements did not change under RBX stimulation (compared to placebo), subjects showed a significant gain in movement speed in visuomotor tasks requiring online-control of precision movements. The results suggest that stimulating the noradrenergic system via RBX does not influence motor performance in general, but rather supports neural circuits involved in visuomotor control of movements.     

The functional long-term results after bilateral sagittal split osteotomy (BSSO) with and without a condylar positioning device.

PURPOSE: The goal of this retrospective study was to examine whether utilization of condylar positioning devices in bilateral sagittal split osteotomy leads to long-term benefits for temporomandibular joint function as compared with the manual positioning technique. PATIENTS AND METHODS: The joint function of 49 patients (98 joints) who underwent bilateral sagittal split osteotomy or bimaxillary osteotomy at the University Hospital of Aachen between 1993 and 2003 was analyzed by recording joint movements with axiography supported by clinical examination of the temporomandibular joint. In 10 patients out of 28 with mandibular advancement and in 10 out of 21 with mandibular setback the Luhr positioning device was used intraoperatively to reproduce the condylar position. The joints of the remaining patients were positioned manually. The received data were statistically evaluated by using unrelated t test at P = .05. RESULTS: In mandibular advancement the manually positioned group showed significantly less signs of temporomandibular disorders, while there were slight advantages in axiographically measured joint track lengths for the patients who were operated with positioning devices. After mandibular setback surgery clinical analysis as well as axiography presented comparable results in both groups. CONCLUSION: The use of a positioning device did not provide a better functional outcome long term in either mandibular advancement or setback surgery. With the manual positioning technique, an at least equally good temporomandibular joint function was attained.     

Behavioral and neural effects of nicotine on visuospatial attentional reorienting in non-smoking subjects.

The cholinergic neurotransmitter system has been proposed to be involved in the processing of probabilistic top-down information provided by endogenous cues in location-cueing paradigms. It has been shown that the behavioral and neural effects of a nicotinic cholinergic stimulation resemble the effects obtained by manipulating the validity of the spatial cues: enhancing cortical nicotine levels and decreasing cue validity both reduce the reaction time difference between invalidly and validly cued targets (ie, the 'validity effect') as well as neural activity related to attentional reorienting in parietal brain regions. In the present study, we investigated whether the behavioral and neural effects of nicotine in location-cueing paradigms are dependent upon different a priori cue validities. Twenty-four subjects were investigated in a double-blind placebo-controlled between-subject design with functional magnetic resonance imaging. Nicotine was administered to non-smoking volunteers via polacrilex gums (Nicorette, 2 mg) before performing a location-cueing paradigm with valid and invalid cues in the context of 90 and 60% cue validity in the MR scanner. Nicotine significantly reduced the validity effect in the 90% but not in the 60% cue validity condition. Fronto-parietal and cingulate regions showed stronger nicotinic reductions of reorienting-related neural activity in the high than in the low cue validity condition. Our data reveal an interaction effect between the pharmacological and cognitive modulation of attentional reorienting, which is evident at both a behavioral as well as the neuronal level.     

Oral inflammatory changes as an initial manifestation of Crohn's disease antedating abdominal diagnosis

The case of a 14-year-old boy who had oral ulcers with histologic proof of granulomatous disease nine months before the diagnosis of intestinal Crohn's disease is presented. Additional extraintestinal manifestations of this case were cheilitis, anal fissures, and “metastatic” disease to the umbilicus. The diagnosis was established after the onset of abdominal symptoms. All manifestations responded rapidly to systemic prednisone, sulfasalazine, and metronidazole.     

Autotransfusion systems (ATS)

Due to the large number of patients undergoing cardiac surgical procedures and the subsequent increase in demand for blood volume replacement, the use of autotransfusion is increasing in the postoperative setting. In a study conducted by Roche and Stengel it was estimated that the country's blood resources could be depleted by these surgical procedures. The use of autotransfusion offers a viable solution for this problem. Studies suggest that with autotransfusion, bank blood requirements may decrease as much as 50 percent. The ready availability and economic advantages associated with autotransfusion may also ensure continued use of systems of this type. It has been the authors' experience thus far that both systems presented have been safe and effective when used in postoperative management of the cardiac surgical patient.     

Mouse monoclonal antibodies reactive with J5 lipopolysaccharide exhibit extensive serological cross-reactivity with a variety of gram-negative bacteria

We describe two mouse monoclonal antibodies reactive with lipopolysaccharide derived from the J5 mutant of Escherichia coli O111:B4. These antibodies react with purified lipopolysaccharide derived from rough mutants of E. coli and Salmonella typhimurium and also with lipopolysaccharide associated with both smooth- and rough-phenotype, gram-negative bacteria. Both antibodies appear to bind determinants present in the lipopolysaccharide core region, and this reactivity is inhibited in the presence of polymyxin B. Although their patterns of reactivity differ, both antibodies exhibit extensive serological cross-reactivity with a variety of gram-negative bacteria. Reagents of this type should prove useful in animal models to delineate the requisite affinity, epitope specificity, immunoglobulin class, etc., needed for the prevention and treatment of gram-negative bacteremia.     

Visual field loss in young children and mentally handicapped adolescents receiving vigabatrin

PURPOSE: In adult patients and in children of school age who have been treated with vigabatrin (VGB), persistent visual field defects have been reported as a side effect. To date, it is unknown to what extent VGB causes visual field loss in young children and mentally handicapped adolescents who cannot be tested with conventional perimetric METHODS: The purpose of the present study was to investigate VGB-induced visual field loss in these patients by using a noncommercial arc perimeter and a forced-choice, preferential-looking method. The visual field size was measured in 30 patients aged 1 to 15 years who had epilepsy and who were treated with VGB. The visual field of these patients was compared to the visual field of 70 control subjects. RESULTS: In eight (27%) patients who had been treated with VGB, the visual field was constricted compared with the visual field of the children belonging to the control group. CONCLUSIONS: Arc perimetry shows that mentally handicapped patients and children younger than 6 years treated with VGB have visual field loss compared with the loss reported in adult patients receiving VGB.