Instantaneous coronary collateral function during supine bicycle exercise

The instantaneous response of the collateral circulation to isometric physical exercise in patients with non-occlusive coronary artery disease (CAD) is not known.

Preclinical testing of strategies for therapeutic targeting of human T-cell trafficking in vivo

Naive T cells are migratory cells that continuously recirculate between blood and lymphoid tissues. Antigen-specific stimulation of T cells within the lymph nodes reprograms the trafficking properties of T cells by inducing a specific set of adhesion molecules and chemokine receptors on their surface which allow these activated and effector T cells to effectively and specifically home to extralymphoid organs. The observations of organ-specific homing of T cells initiated the development of therapeutic strategies targeting adhesion receptors for organ-specific inhibition of chronic inflammation. As most adhesion receptors have additional immune functions besides mediating leukocyte trafficking, these drugs may have additional immunomodulatory effects. Therapeutic targeting of T-cell trafficking to the central nervous system is the underlying concept of a novel treatment of relapsing remitting multiple sclerosis with the humanized anti-alpha-4-integrin antibody natalizumab. In this chapter, we describe a possible preclinical in vivo approach to directly visualize the therapeutic efficacy of a given drug in inhibiting T-cell homing to a certain organ at the example of the potential of natalizumab to inhibit the trafficking of human T cells to the inflamed central nervous system in an animal model of multiple sclerosis.

Risk factors for geriatric patient falls in rehabilitation hospital settings: a systematic review

Objective: To review the literature to identify and synthesize the evidence on risk factors for patient falls in geriatric rehabilitation hospital settings. Data sources: Eligible studies were systematically searched on 16 databases from inception to December 2010. Review methods: The search strategies used a combination of terms for rehabilitation hospital patients, falls, risk factors and older adults. Cross-sectional, cohort, case-control studies and randomized clinical trials (RCTs) published in English that investigated risks for falls among patients ≥65 years of age in rehabilitation hospital settings were included. Studies that investigated fall risk assessment tools, but did not investigate risk factors themselves or did not report a measure of risk (e.g. odds ratio, relative risk) were excluded. Results: A total of 2,824 references were identified; only eight articles concerning six studies met the inclusion criteria. In these, 1,924 geriatric rehabilitation patients were followed. The average age of the patients ranged from 77 to 83 years, the percentage of women ranged from 56% to 81%, and the percentage of fallers ranged from 15% to 54%. Two were case-control studies, two were RCTs and four were prospective cohort studies. Several intrinsic and extrinsic risk factors for falls were identified. Conclusion: Carpet flooring, vertigo, being an amputee, confusion, cognitive impairment, stroke, sleep disturbance, anticonvulsants, tranquilizers and antihypertensive medications, age between 71 and 80, previous falls, and need for transfer assistance are risk factors for geriatric patient falls in rehabilitation hospital settings.

Early and late urodynamic assessment of ileal orthotopic bladder substitutes combined with an afferent tubular segment

PURPOSE: Limited information is available concerning changes in the urodynamic characteristics of orthotopic bladder substitutes with time. Therefore, we compared early and late urodynamic results in patients with an ileal orthotopic bladder substitute combined with an afferent tubular segment. MATERIALS AND METHODS: Of 139 patients surviving at least 5 years after cystoprostatectomy and ileal orthotopic bladder substitution with an afferent tubular segment 119 underwent urodynamic assessment, including 66 at a median of 9 months (early) and 77 at a median of 62 months (late). Of these patients 24 were assessed at each time point. Simultaneously all patients were asked to complete a bladder diary and questionnaire regarding continence for at least 3 days in the week preceding the urodynamic study. RESULTS: Urodynamic parameters were comparable in patients who were evaluated early and late postoperatively. In addition, median values at early and late urodynamic evaluation in the 24 patients with the 2 examinations showed no statistically significant differences for volume at first desire to void (300 vs 333 ml, p = 0.85), pressure at first desire to void (12 vs 13 cm H2O, p = 0.57), maximum cystometric capacity (450 vs 453 ml, p = 0.84), end filling pressure (19 vs 20 cm H2O, p = 0.17), reservoir compliance (25 vs 28 ml/cm H2O, p = 0.58) or post-void residual urine volume (5 vs 15 ml, p = 0.27). CONCLUSIONS: Urodynamic results after 5 years of living with an ileal orthotopic bladder substitute with an afferent tubular segment show grossly unchanged urodynamic characteristics. Patients maintain a reservoir capacity and micturition pattern consistent with a normal life-style. Reservoir pressure remained low, thereby protecting and preserving upper tract function. To achieve these results patients must be regularly followed, and the causes of bacteriuria, increased post-void residual urine and bladder outlet obstruction must be recognized and dealt with accordingly.

A comparative assessment of endothelium from pseudophakic and phakic donor corneas stored in organ culture

AIMS To evaluate the endothelial quality of corneas obtained from pseudophakic donors and to compare the data with matched phakic controls. METHODS Corneas from eyes with posterior chamber intraocular lenses (PCIOLs) and corneas from phakic eyes (controls) were stored for 1-2 weeks in organ culture and then examined after staining with Alizarin red S. The corneas were divided into two groups according to the duration of storage. Endothelial cell density, the percentage of hexagonal cells, and the coefficient of variation (CV) were determined. RESULTS There was no statistically significant difference between the 14 PCIOL corneas and the 13 controls stored in organ culture for 7 days for any of the three parameters studied. The mean cell density was 2155 (SD 529) cells/mm(2) in the PCIOL corneas and 2118 (453) cells/mm(2) in the controls (p=0.85). The mean percentage of hexagonal cells was 52% (8%) and 58% (7%), respectively (p=0.06). The mean CV was 0.32 (0.18) in the pseudophakic corneas and 0.39 (0.18) in the controls (p=0.33). Moreover, there was no significant difference between the PCIOL corneas and the controls stored for up to 2 weeks. CONCLUSIONS The corneal endothelium from eyes with PCIOLs appears to be similar to that of phakic eyes after 1-2 weeks in organ culture. This finding suggests that corneas from pseudophakic eyes should not routinely be disqualified for transplantation. The use of at least some pseudophakic corneas may substantially increase the potential donor pool.

Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents.

BACKGROUND Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain. METHODS Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug (clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding. RESULTS A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo. Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis (0.4% vs. 1.4%; hazard ratio, 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85]; P<0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo (2.1% vs. 4.1%; hazard ratio, 0.47; P<0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group (hazard ratio, 1.36 [95% CI, 1.00 to 1.85]; P=0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment (2.5% vs. 1.6%, P=0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment. CONCLUSIONS Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. (Funded by a consortium of eight device and drug manufacturers and others; DAPT ClinicalTrials.gov number, NCT00977938.).

Exercise capacity, physical activity patterns and outcomes six years after cardiac rehabilitation in patients with heart failure.

OBJECTIVE To determine the short- and long-term effects of an intensive, concentrated rehabilitation programme in patients with chronic heart failure. DESIGN Randomized controlled trial, with one-month and six-year evaluations. SETTING Residential rehabilitation centre in Switzerland. SUBJECTS Fifty patients with chronic heart failure, randomized to exercise or control groups. INTERVENTIONS A rehabilitation programme lasting one month, including educational sessions, a low-fat diet, and 2 hours of individually prescribed exercise daily. MAIN MEASURES Exercise test responses, health outcomes and physical activity patterns. RESULTS Peak Vo(2) increased 21.4% in the exercise group during the rehabilitation programme (P<0.05), whereas peak Vo(2) did not change among controls. After the six-year follow-up period, peak Vo(2) was only slightly higher than that at baseline in the trained group (7%, NS), while peak Vo(2) among controls was unchanged. During long-term follow-up, 9 and 12 patients died in the exercise and control groups, respectively (P = 0.63). At six years, physical activity patterns tended to be higher in the exercise group; the mean energy expenditure values over the last year were 2,704 +/- 1,970 and 2,085 +/- 1,522 kcal/week during recreational activities for the exercise and control groups, respectively. However, both groups were more active compared to energy expenditure prior to their cardiac event (P<0.001). CONCLUSIONS Six years after participation in a residential rehabilitation programme, patients with chronic heart failure had slightly better outcomes than control subjects, maintained exercise capacity and engaged in activities that exceed the minimal amount recommended by guidelines for cardiovascular health.

Plate fixation of extra-articular fractures of the proximal phalanx: do new implants cause less problems?

BACKGROUND Limited range of finger motion is a frequent complication after plate fixation of phalangeal fractures. The purpose of this study was to evaluate the results of plate fixation of extra-articular fractures of the proximal phalanx using current low-profile mini-fragment-systems. METHODS From 2006 to 2012, 32 patients with 36 extra-articular fractures of the proximal phalanx of the triphalangeal fingers were treated with open reduction and plate fixation (ORPF) using 1.2 and 1.5 mm mini-fragment systems. Patients presenting with open fractures grade 2 and 3 or relevant laceration of adjacent structures were excluded from the study. We retrospectively evaluated the rate of mal-union or non-union after ORPF, the need for revision surgery, for plate removal, and for tenolysis. Data were analyzed for further complications with regard to infections or complex regional pain syndrome (CRPS). RESULTS No infections were noted. Five patients developed transient symptoms of CRPS. Six weeks postoperatively, total active finger motion (TAM) averaged 183°, and all 32 patients underwent formal hand therapy. At the latest follow-up or at the time of plate removal, respectively, the mean TAM improved to 213°. Extension lag of proximal interphalangeal joints was found in 67 % of all fractured fingers. Secondary surgery was necessary in 14 of 32 patients (2 corrective osteotomies, 12 plate removals including 7 procedures explicitly because of reduced mobility). CONCLUSIONS Despite of new implant designs significant problems persist. Adhesions of extensor tendons leading to limited range of finger motion are still the most frequent complications after ORPF of proximal phalangeal fractures, even in absence of significant soft-tissue damage. LEVEL OF EVIDENCE Therapeutic, Retrospective, Level IV.

Monitoring the Chemical State of Catalysts for CO 2 Electroreduction: An In Operando Study

A major concern of electrocatalysis research is to assess the structural and chemical changes that a catalyst may itself undergo in the course of the catalyzed process. These changes can influence not only the activity of the studied catalyst but also its selectivity toward the formation of a certain product. An illustrative example is the electroreduction of carbon dioxide on tin oxide nanoparticles, where under the operating conditions of the electrolysis (that is, at cathodic potentials), the catalyst undergoes structural changes which, in an extreme case, involve its reduction to metallic tin. This results in a decreased Faradaic efficiency (FE) for the production of formate (HCOO–) that is otherwise the main product of CO2 reduction on SnOx surfaces. In this study, we utilized potential- and time-dependent in operando Raman spectroscopy in order to monitor the oxidation state changes of SnO2 that accompany CO2 reduction. Investigations were carried out at different alkaline pH levels, and a strong correlation between the oxidation state of the surface and the FE of HCOO– formation was found. At moderately cathodic potentials, SnO2 exhibits a high FE for the production of formate, while at very negative potentials the oxide is reduced to metallic Sn, and the efficiency of formate production is significantly decreased. Interestingly, the highest FE of formate production is measured at potentials where SnO2 is thermodynamically unstable; however, its reduction is kinetically hindered.

Oxygen Reduction Reaction on Pt Overlayers Deposited onto a Gold Film: Ligand, Strain, and Ensemble Effect

We study the oxygen reduction reaction (ORR), the catalytic process occurring at the cathode in fuel cells, on Pt layers prepared by electrodeposition onto an Au substrate. Using a nominal Pt layer by layer deposition method previously proposed, imperfect layers of Pt on Au are obtained. The ORR on deposited Pt layers decreases with increasing Pt thickness. In the submonolayer region, however, the ORR activity is superior to that of bulk Pt. Using density functional theory (DFT) calculations, we correlate the observed activity trend to strain, ligand, and ensemble effects. At submonolayer coverage certain atom configurations weaken the binding energies of reaction intermediates due to a ligand and ensemble effect, thus effectively increasing the ORR activity. At higher Pt coverage the activity is governed by a strain effect, which lowers the activity by decreasing the oxidation potential of water. This study is a nice example of how the influence of strain, ligand, and ensemble effects on the ORR can be deconvoluted.