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C Weiss

Publications and source records attributed to C Weiss.

At least 73 records · Page 4Linked to original sources

The classic nail in the therapy of trochanteric fractures.A prospective, controlled study.

In a prospective controlled study we analysed the classic nail, a new intramedullary implant for the fixation of peritrochanteric fractures. By means of lateral bending of 4 degrees, unreamed implantation is generally possible. Our collective of 85 patients was characterized by elderly mean age (82.3 years), a predominance of female patients (4.3 : 1), a minor trauma aetiology without relevant additional injuries, and a high rate of concomitant disease (92%). Only 31A-type femur fractures were treated, with a low specific complication rate of 13%, whereby operative revision was necessary in only two patients (3%). A good anatomic reconstruction and full weight-bearing with the osteosynthesis was achieved in the majority of patients. No secondary shaft fractures and only one case of cutting out was observed. The mortality (30 days: 18%, 6 months: 25%) as well as the high rate of unspecific complications (20%) were caused by the patients' multiple morbidity. Deficits in the Merle d'Aubigne score at follow-up after 6 months can be interpreted within the same context. Nevertheless, 85% could return to their former social environment and only 15% became dependent on a nursing institution in connection with the fracture treatment.

Aged↗

Cholinergic facilitation of trace eyeblink conditioning in aging rabbits.

The hippocampus is importantly involved in learning and memory, and is severely impacted by aging. In in vitro hippocampal slices, both the post-burst afterhyperpolarization (AHP) and spike-frequency accommodation are reduced in hippocampal pyramidal neurons after hippocampally-dependent trace eyeblink conditioning, indications of increased cellular excitability. The AHP results from the activation of outward potassium currents, including sI(AHP) and muscarine-sensitive I(M). The AHP is significantly increased in aging hippocampal neurons, potentially contributing to age-associated learning deficits. Compounds which reduce the AHP and spike-frequency accommodation could facilitate learning in normal aging or in age-associated dementias such as Alzheimer's disease. The cholinesterase inhibitor metrifonate enhances trace eyeblink conditioning by aging rabbits and reduces the AHP and accommodation in hippocampal CA1 neurons in a dose-dependent manner. These reductions are mediated by muscarinic cholinergic transmission as they are blocked by atropine. Hippocampal neurons from metrifonate treated but behaviorally naive rabbits were more excitable and not desensitized to the effects of metrifonate since the AHP and accommodation were further reduced when metrifonate was bath applied to the neurons. These observations suggest that the facilitating effect of chronic metrifonate on acquisition of hippocampally dependent tasks is mediated at least partially by increasing the baseline excitability of CA1 pyramidal neurons. The issue of whether learning can be facilitated with muscarinic cholinergic agonists, in addition to cholinesterase inhibitors, was addressed by training aging rabbits during intravenous treatment with the M1 agonist CI1017. A dose-dependent enhancement of acquisition was observed, with rabbits receiving 1.0 or 5.0 mg/ml CI1017 showing comparably improved learning rates as those receiving 0.5 mg/ml or vehicle. Sympathetic side effects, mainly excess salivation, were seen with the 5.0 mg/ml dose. Post-training evaluations suggested that the effective doses of CI1017 were enhancing responsivity to the tone conditioned stimulus. These studies suggest that muscarinic cholinergic neurotransmission is importantly involved in associative learning; that learning in aging animals may be facilitated by enhancing cholinergic transmission; and that the facilitation may be mediated through actions on hippocampal neurons.

Acetylcholine↗

IL-9 pathway in asthma: new therapeutic targets for allergic inflammatory disorders.

BACKGROUND: Asthma is a complex heritable inflammatory disorder of the airways associated with clinical signs of allergic inflammation and bronchial hyperresponsiveness (BHR). The incidence of asthma continues to rise in industrialized countries despite advances in the identification of cellular and molecular mediators that are associated with the disease. Because of its importance in human health, additional research and alternative therapeutic strategies are justified to create more effective treatments for this debilitating disease. OBJECTIVE: Studies use recombinant inbred mice to demonstrate that BHR in mouse models of asthma is associated with a genetic alteration at the IL-9 locus, where IL-9 expression in lung is strongly associated with bronchial responsiveness. We have investigated the ability of intratracheal instilled IL-9 to induce asthmatic-like responses in naive C57BL/6 (B6) mice, which express very low levels of IL-9. METHODS: IL-9 or vehicle was intratracheal instilled in naive B6 mice for 10 days. Mice were analyzed for effects on BHR, lung eosinophilia, and serum total IgE levels. RESULTS: Phenotypic effects of B6 mice instilled with IL-9 were increased eosinophils in the bronchoalveolar lavage and significantly elevated serum total IgE. Moreover, IL-9 was found to induce IL-5Ralpha in vivo and in vitro, suggesting a potential mechanism for the novel actions described for IL-9 on eosinophils. CONCLUSION: Increased levels of IL-9 in the airway of naive B6 mice induced lung eosinophilia and serum total IgE levels, which are 2 clinical features of asthma. These data support a central role for the IL-9 pathway in the complex pathogenesis of allergic inflammation.

Animals↗

Hippocampal lesions prevent trace eyeblink conditioning in the freely moving rat.

The effect of hippocampal aspiration lesions on trace eyeblink conditioning was examined in young, freely-moving F1 hybrid rats (Fisher 344 x Brown Norway). Rats which received either bilateral neocortical or bilateral hippocampal aspiration lesions were compared with each other or with sham lesioned control rats. The rats were trained with a 250 ms tone conditioning stimulus (CS), a 250 ms stimulus free trace interval and a 100 ms corneal airpuff unconditioned stimulus (US). Rats with lesions of the hippocampus were significantly impaired relative to the neocortical and sham lesioned control rats. Analyses of different behavioral parameters (e.g. percent conditioned responses, amplitude, and area of response) indicated that all of the measures for the conditioned response were significantly impaired by the hippocampal lesion. The unconditioned response was not significantly affected by the lesion, and there was no significant difference among the groups after 2 days of subsequent conditioning with the delay paradigm (zero trace interval). We conclude that the hippocampus is required for rats to learn the association between a tone CS and an airpuff US when a 250 ms trace interval is interposed between the two stimuli.

Adaptation, Physiological↗

Trace eyeblink conditioning in the freely moving rat: optimizing the conditioning parameters.

Trace eyeblink conditioning (EBC) parameters, with an airpuff unconditioned stimulus, were examined in male Fischer 344 X Brown Norway F1 rats. Integrated electromyographic activity from the upper eyelid was recorded. An 8-kHz tone was superior to white noise as a conditioning stimulus. Rats trained with 30 or 50 trials per session showed similar learning. Reversal of environmental lighting had no significant effect. Trace intervals of 0 and 250 ms yielded well-timed conditioned responses (CRs); intervals of 500 ms or more did not. These experiments provide parameters that reliably yield CRs and suggest limits on the temporal processing capabilities of the rat. EBC can thus be used as part of a comprehensive test battery for learning and memory in this species. Physiological recording and pharmacological manipulations may also be done easily. This combination of approaches should facilitate a more complete understanding of learning mechanisms and age-related memory impairments.

Animals↗

Histochemical changes in muscle of individuals with spinal cord injury following functional electrical stimulated exercise training.

STUDY DESIGN: Longitudinal training. OBJECTIVES: To determine the effects of functional electrical stimulated (FES) leg cycle ergometer training on muscle histochemical characteristics in individuals with motor-complete spinal cord injury (SCI). SETTING: University of Alberta, Edmonton, Alberta, Canada. METHODS: Six individuals with motor-complete SCI (age 31-50 years; 3-25 years post-injury) trained using FES leg cycle ergometry for 30 min, 3 days per week for 8 weeks. Biopsies of the vastus lateralis muscle were obtained pre- and post-training and analyzed for fibre composition, fibre size and capillarization. RESULTS: The majority of muscle fibres were classified as type 2 pre- and post-training. Average fibre area increased 23% (P<0.05) and capillary number increased 39% (P<0.05) with training. As a result of these proportional increases, capillarization expressed relative to fibre area was unchanged with training. CONCLUSIONS: FES leg cycle ergometer training results in proportional increases in fibre area and capillary number in individuals with SCI.

Adult↗

Impact of the ECG for detection of intraatrial conduction block after atrial flutter ablation.

Induction of complete bidirectional conduction block via the posterior isthmus of the right atrium is introduced as a standard endpoint for catheter ablation of atrial flutter. The present study sought to investigate the impact of changes in P wave duration and morphology detected by the surface ECG during coronary sinus and posterolateral right atrial stimulation as a marker for conduction block. Morphology and duration changes of the paced P wave before and after radiofrequency catheter (RFC) ablation were estimated in 22 patients referred for ablation of atrial flutter. We looked for a morphology change of the terminal portion in the 12-lead ECG and an increment of P wave duration. In 16 of 22 patients in whom atrial flutter ablation resulted in a complete bidirectional block, the conduction block was unidirectional in 4 patients and conduction times remained unchanged in 2 patients. After induction of complete bidirectional block a change of the terminal portion of the P wave towards a more positive morphology in one or more inferior leads was detected in 14 (88%) of 16 patients during coronary sinus stimulation and in 15 (94%) of 16 patients during posterolateral right atrial stimulation. These changes were predominantly observed in the inferior leads. Positive morphology changes of the terminal P wave portion in the inferior leads indicating conduction block with a sensitivity of 86% and a specificity of 100% were observed. An increment of 10 ms or more in P wave duration indicates conduction block with a specificity of 100% and a sensitivity of 67%. There was a significantly larger increment of P wave duration during coronary sinus (CS) stimulation compared to posterolateral right atrial stimulation (38 +/- 21 vs 16 +/- 21 ms). The analysis of P wave duration and morphology in the inferior leads of the surface ECG is a reliable tool to assess the intraatrial conduction after atrial flutter ablation. Different conduction during coronary sinus and posterolateral right atrial pacing may cause a different P wave duration after ablation.

Aged↗

Atrial flutter ablation using a technique for detection of conduction block within the posterior isthmus.

Catheter ablation orientated on the induction of a functional intraatrial block within the posterior isthmus of the tricuspid annulus has been shown to effectively abolish atrial flutter. In order to improve and simplify the current technique, a strategy based on an electrode catheter for combined right atrial and coronary sinus mapping and stimulation was explored prospectively. Twenty-four consecutive patients referred for catheter ablation of recurrent type I atrial flutter were included. A steerable 7 Fr catheter (Medtronic/Cardiorhythm) composed of two segments with 20 electrodes was used for right atrial and coronary sinus activation mapping and stimulation. Multiple steering mechanisms allowing intubation and positioning of the distal part within the coronary sinus were incorporated into the device. Adequate positioning of the mapping catheter was achieved solely via a transfemoral approach in all patients after 7.7 +/- 4.6 minutes, providing stable electrogram recordings during the entire ablation procedure. Radiofrequency current ablation (16.3 +/- 9.6 pulses) caused a significant bidirectional increase of the mean intraatrial conduction times via the posterior isthmus irrespective to the stimulation interval. Significant changes of intraatrial conduction properties were induced during ablation in 22 of 24 patients (bidirectional block: n = 18, unidirectional block: n = 3, conduction delay: n = 1, unchanged conduction: n = 2). Following ablation atrial flutter was noninducible in all patients. Twenty-two of 24 patients (92%) remained free of atrial flutter episodes during a follow-up of 12.5 +/- 5.7 months. Two of six patients without a bidirectional conduction block had a recurrence of atrial flutter. Atrial flutter ablation guided by the induction of an intraatrial conduction block can be effectively performed with this novel strategy for combined mapping of the posterior tricuspid isthmus, including coronary sinus and right atrial free wall. This transfemoral approach has a high accuracy with respect to the detection of radiofrequency current-induced changes of intraatrial conduction patterns.

Atrial Flutter↗

Two wavelength femtosecond laser induced DNA-protein crosslinking.

Nucleic acid-protein interactions are essential for storage, reproduction and expression of genetic information. Biochemical methods, such as dimethyl sulfate genomic footprinting, have been developed to study stable protein-DNA interactions in vivo and chemical crosslinking has been used for less stable interactions, but the chemical agents are slow, damage cells and perturb native equilibria. To avoid these perturbations, UV laser crosslinking offers an alternative, although the energies required for significant crosslinking cause extensive DNA damage. We find that a combination of femtosecond laser pulses at two different wavelengths, in the UV and the visible range, increases the crosslinking efficiency while minimizing DNA damage. This technique also allowed us to directly measure the singlet S1lifetime of native DNA (tauS1 = 3.2 +/- 0.2 ps), which is mainly determined by the lifetime of thymine [tauS1 = 2.8 +/- 0.4 ps for (dT)16], the photochemically most reactive base. Our results suggest that two wavelength femtosecond laser pulses are well suited for the identification of transcription factors interacting with defined sequences and for studying the kinetics of protein-nucleic acid interactions in intact cells.

DNA↗

Activation of coagulation and fibrinolysis after rehabilitative exercise in patients with coronary artery disease.

It has been suggested that blood coagulation be activated and fibrinolytic activity be impaired in patients with coronary artery disease (CAD). With regard to the activation of coagulation and fibrinolysis occurring during exercise in healthy individuals, we examined the hypothesis that rehabilitative exercise in patients with CAD might give rise to an exaggerated activation of coagulation. In 12 patients with angiographically documented CAD without myocardial infarction within the preceding 6 months (male, age 55+/-9 years [SD]) and in 12 healthy controls (male, 52+/-7 years), molecular markers of thrombin, fibrin, and plasmin formation were determined before and after a rehabilitative group exercise session lasting 1 hour. Resting levels of prothrombin fragment 1+2 were lower in patients with CAD (0.67+/-0.2 [SE] vs 1.04+/-0.2 nmol/L, p <0.001) and remained unchanged after exercise, whereas a significant increase was noted in controls (p <0.01). After exercise, plasma levels of thrombin-antithrombin III complexes and of fibrinopeptide A increased significantly in both groups, although there were more pronounced changes in controls. Exercise resulted in a marked generation of plasmin as indicated by plasmin-alpha2-antiplasmin complexes increasing 2.5-fold in patients (p <0.001) and threefold in controls (p <0.001). Repeated experiments in control subjects after administration of aspirin (day 1: 500 mg; days 2 to 5: 100 mg) documented that differences between groups could not be attributed to aspirin medication (100 mg/day) in patients with CAD. We concluded that rehabilitative exercise in patients with CAD beyond the immediate postinfarction period has no detrimental effects on thrombin, fibrin, and plasmin formation.

Adult↗

Hippocampectomy disrupts auditory trace fear conditioning and contextual fear conditioning in the rat.

The hippocampus is believed to be an important structure for learning tasks that require temporal processing of information. The trace classical conditioning paradigm requires temporal processing because the conditioned stimulus (CS) and the unconditioned stimulus (US) are temporally separated by an empty trace interval. The present study sought to determine whether the hippocampus was necessary for rats to perform a classical trace fear conditioning task in which each of 10 trials consisted of an auditory tone CS (1 5-s duration) followed by an empty 30-s trace interval and then a fear-producing floor-shock US (0.5-s duration). Several weeks prior to training, animals were anesthetized and given aspiration lesions of the neocortex (NEO; n = 6), hippocampus and overlying neocortex (HIPP; n = 7), or no lesions at all (control; n = 6). Approximately 24 h after trace conditioning, NEO and control animals showed a significant decrease in movement to a CS-alone presentation that was indicative of a conditioned fear response. Animals in the HIPP group did not show conditioned fear responses to the CS alone, nor did a pseudoconditioning group (n = 7) that was trained with unpaired CSs and USs. Furthermore, all groups except the HIPP group showed conditioned fear responses to the original context in which they received shock USs. One week later, HIPP, NEO, and control animals received delay fear-conditioning trials with no trace interval separating the CS and US. Six of seven HIPP animals could perform the delay version, but none could perform the trace version. This result suggests that the trace fear task is a reliable and useful model for examining the neural mechanisms of hippocampally dependent learning.

Acoustic Stimulation↗

[High frequency current ablation of ectopic atrial tachycardia. Different mapping strategies for localization of right- and left-sided origin].

UNLABELLED: Ectopic atrial tachycardia (EAT) is a rare form of supraventricular tachycardia and often drug-resistant. Radiofrequency catheter (RFC) ablation offers an alternative therapy suggesting a high efficacy rate. Localization of the EAT origin is proposed to be efficacious by various mapping strategies. We analyzed the efficacy of different mapping strategies for localization of right and left sided EAT foci. METHODS AND PATIENTS: In a cohort of 48 patients (25 female: age 35 +/- 18 years) RFC ablation of 40 right and 12 left sided EAT foci was performed. Mapping of the right atrium was achieved with 2 ablation catheters using the "encircling" technique (Figure 1). We looked for an early bipolar local electrogram in relation to the onset of the P-wave and a QS-complex in the unipolar electrogram. The bipolar local electrogram was retrospectively analyzed for a fragmented morphology and duration of more than 50 ms (Figure 3). In case of mechanical block of the EAT during mapping P-wave pace mapping over the mapping catheter was performed (Figure 4). RESULTS: RFC ablation succeeded in 44 patients with 46 EAT foci (Figure 5). Left sided EAT origin was in 40% in the region of the pulmonary veins. Two left sided foci were abladed within the coronary sinus. An anteroseptal location in vicinity to the bundle of His was found in 4 cases (Figure 6). There were no differences between left and right sided origin regrading session duration (304 +/- 131 vs 241 +/- 101 min) and fluoroscopic time (39 +/- 29 vs 31 +/- 19 min). The activation time related to the onset of the P-wave was at successful ablation site for left sided origin significantly earlier compared to a right sided origin (45 +/- 22 vs 30 +/- 18 ms). Fragmenation of the bipolar local electrogram was found before successful RFC application in 86% in the left and in 65% in the right atrium. The unipolar electrogram showed in 87% of all cases a QS-complex before the successful RFC pulse. In 16% a beat to beat change of the unipolar electrogram could be found at successful ablation site (Figure 7). Both criteria had a low specify and sensitivity. Mechanical block could be induced during mapping in 10 patients (20%). In these cases RFC application at a site with a perfect match of P-wave pace mapping succeeded in 8 patients. In 2 patients the same EAT occurred within the following 24 hours. During a follow-up of 4 to 58 months there were additionally recurrence of EAT in 3 patients (3 to 6 months after ablation). No influence of the AV nodal conduction was observed after ablation of anteroseptal EAT foci. Other acute or chronic complications were not observed. CONCLUSIONS: 1. RFC ablation of right and left sided EAT foci is a safe and efficacious treatment. There were no differences regarding session duration and fluoroscopic time between right and left sided foci. 2. Activation mapping showed an earlier activation time for left sided origin compared to right sided. 3. Mechanical block could be induced in 20% of cases. P-wave pace mapping might offer a strategy to localize the focus during mechanical block.

Adolescent↗

Whole-body hyperthermia combined with ifosfamide and carboplatin causes hypotension and nephrotoxicity.

It was previously postulated on the basis of clinical data that the cardiovascular sequelae of extracorporeal whole-body hyperthermia (e-WBH), i.e., hypotension (which requires catecholamine support) results in unique nephrotoxicity in combination with select chemotherapeutic agents. In an attempt to explain this phenomenon, we mimicked e-WBH physiological conditions in a rat model. Animals were treated with and without ifosfamide (IFO) and/or carboplatin (CBDCA) at 37 degrees C or 41.5-41.8 degrees C, with blood pressure monitoring and catecholamine support comparable to the clinical setting. Ex vivo post-treatment data (24 h) from artificially perfused kidneys (i.e., histology, urine volume, perfusion rate, glomerular filtration rate, and the reabsorption of sodium, glucose, and water) demonstrated unique toxicity including proximal tubular necrosis for the combination of WBH and IFO, for WBH and CBDCA and for WBH and IFO plus CBDCA, but not for IFO and CBDCA without WBH. These data, considered together with results derived from a subsequent clinical trial and the laboratory work of others were consistent with the hypothesis.

Animals↗