The use of telescoping guide catheters for coronary sinus cannulation and sub-selecting tributaries in left ventricular lead placement

Introduction Failure to enter the coronary sinus (CS) with a guiding catheter and entering its tributaries remains challenging in left ventricle (LV) pacing lead implants for cardiac resynchronization therapy (CRT). A dual telescoping catheter system (8F outer/6F inner) is designed to provide the ability to adjust the catheter curve size, shape and/or reach to the patients’ anatomy avoiding the need for catheter change. Methods Five different designs for CS cannulation were randomly tested in 64 patients scheduled for CRT device implant. Results In 33 consecutive patients three adaptable telescoping guiding catheter systems were tested per patient, the adaptable catheters had higher overall cannulation success rates (68, 63 and 62%) compared to the fixed shape catheter (46%) and an greater cannulation success rate when the CS location was not known (70, 53 and 72% vs 33% for the fixed shape). In a second group of 31 CRT patients the two telescoping catheters had similar high levels of success (71–80%), with or without using the inner catheter. Conclusions The telescopic system is adaptable to a wide range of anatomical variations in patients and can result in a higher CS cannulation success rate due to its adjustability in the RA in search for the CS ostium. On top of this the inner catheter allows for sub-selecting the CS tributaries.     

The effect of lateralized dynamic stimuli on unilateral spatial neglect following right hemisphere lesions

Patients with unilateral (left-sided) spatial neglect following right-hemisphere stroke were tested for the effects of visual stimulation on performance of a line-bisection task. As predicted from research on brain mechanisms of spatial orientation and attention, dynamic visual stimuli presented on the left side substantially reduced neglect in the task. In contrast, left sided static stimuli reduced neglect significantly less and dynamic stimuli presented in the center had no effect on neglect. Neglect patients with hemianopia did not show significantly less benefit of left-sided dynamic stimuli compared to neglect patients without hemianopia, suggesting that the effect of these stimuli was unconscious and automatic. The potential advantages of lateralized dynamic stimuli in the rehabilitation of neglect are discussed.     

Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability

The assumed metabolic breakdown of albendazole by mucosal CYP3A4 enzymes was studied by coadministering albendazole (10 mg/kg) with grapefruit juice. Concentrations of albendazole sulfoxide (ABZSX), the active metabolite of albendazole, were compared with those after albendazole was administered with water, a fatty meal, or grapefruit juice plus cimetidine (10 mg/kg). In comparison to water, maximum ABZSX concentration (Cmax) was enhanced 6.5-fold by a fatty meal (from 0.24 +/- 0.09 mg/l to 1.55 +/- 0.30 mg/l; mean +/- SD; P < 0.001) and 3.2-fold by grapefruit juice (from 0.24 +/- 0.09 mg/l to 0.76 +/- 0.37 mg/L; P = 0.031). When grapefruit juice was combined with cimetidine, Cmax was significantly lower than with grapefruit juice alone (0.41 +/- 0.29 mg/l and 0.76 +/- 0.37 mg/l, respectively; P = 0.022). The area under the concentration-time curve from 0 to infinity (AUC(0-omega)) followed a comparable pattern. Half-life (T(1/2)) was 8.8 +/- 4.2 hr and 8.2 +/- 4.3 hr after administration with water or a fatty meal (P = 1.000). Grapefruit juice shortened T(1/2) by 46% (P = 0.026). We hypothesize that albendazole is metabolized by CYP3A4 enzymes in the intestinal mucosa. This process can be inhibited by grapefruit juice. Cimetidine decreased albendazole bioavailability.     

Right Ventricular Longitudinal Strain Predicts Survival in Patients With Functional Tricuspid Regurgitation

BackgroundFunctional tricuspid regurgitation (TR) is a frequent finding in echocardiography. Despite general consent that right ventricular (RV) dysfunction impacts outcome of patients with TR, it is still unknown which echocardiographic parameters most accurately reflect prognosis. In this study we aimed to evaluate the prevalence of RV dysfunction and its prognostic value in patients with TR.MethodsData from 1089 consecutive patients were analysed. Tricuspid annular plane systolic excursion (TAPSE), fractional area change, and right ventricular free wall longitudinal strain (RV strain) were used to define RV dysfunction. Patients were followed for 2-year all-cause mortality. For prediction of survival, reclassification and C statistics of RV functional parameters using TR grade as reference model were performed.ResultsAmong the patients studied, 13.9% showed no TR, 61.2% had mild TR, 19.6% had moderate TR, and 5.3% had severe TR. The TR grade was associated with increased mortality (log rank, P < 0.001). Impaired RV strain and TAPSE were independent predictors for mortality (RV: hazard ratio [HR], 1.130; 95% confidence interval [CI], 1.099-1.160; P < 0.001; TAPSE: HR, 1.131; 95% CI, 1.085-1.175; P < 0.001). Both RV strain and TAPSE improved the reference model for survival prediction (RV: integrated discrimination improvement [IDI], 0.184; 95% CI, 0.146-0.221; P < 0.001; TAPSE: IDI, 0.057; 95% CI, 0.037-0.077; P < 0.001).ConclusionsEchocardiographic evaluation of RV function appears to useful for patients with TR. Assessment of RV strain provides additional value for prediction of 2-year mortality.     

Alterations in erythrocyte rheology in patients with severe peripheral vascular disease: 1. Cell volume dependence of erythrocyte rigidity

The erythrocyte rigidity of patients suffering from severe peripheral vascular disease (PVD) was measured by a filtration method using 3 microns pore size filters. Filtration pressures for both PVD patients and normal subjects showed a cell volume dependency, and patient filtration pressures were normalized to cell volume to evaluate intrinsic, ie, nonvolume dependent, abnormalities in erythrocyte deformability. A significant (p less than 0.001) increase in cell rigidity was found in 44 of 54 PVD patients in comparison with volume-matched normal controls. No significant difference was found between patient mean corpusculer hemoglobin (MCH) and normal MCH at any given mean corpuscular volume (MCV), indicating that observed increases in erythrocyte rigidity are not attributable to changes in patient MCH. Therefore, the mechanism of increase in erythrocyte rigidity for PVD patients still needs further investigation into such parameters as levels of adenosine triphosphate,2,3-DPG, and membrane fluidity (calcium- and/or protein-binding membrane, cholesterol and phospholipid content of membrane, etc), as well as other aspects of erythrocyte physiology.     

A Tissue-Specific Role for Nlrp3 in Tubular Epithelial Repair after Renal Ischemia/Reperfusion

Ischemia/reperfusion injury is a major cause of acute kidney injury. Improving renal repair would represent a therapeutic strategy to prevent renal dysfunction. The innate immune receptor Nlrp3 is involved in tissue injury, inflammation, and fibrosis; however, its role in repair after ischemia/reperfusion is unknown. We address the role of Nlrp3 in the repair phase of renal ischemia/reperfusion and investigate the relative contribution of leukocyte- versus renal-associated Nlrp3 by studying bone marrow chimeric mice. We found that Nlrp3 expression was most profound during the repair phase. Although Nlrp3 expression was primarily expressed by leukocytes, both leukocyte- and renal-associated Nlrp3 was detrimental to renal function after ischemia/reperfusion. The Nlrp3-dependent cytokine IL-1β remained unchanged in kidneys of all mice. Leukocyte-associated Nlrp3 negatively affected tubular apoptosis in mice that lacked Nlrp3 expression on leukocytes, which correlated with reduced macrophage influx. Nlrp3-deficient (Nlrp3KO) mice with wild-type bone marrow showed an improved repair response, as seen by a profound increase in proliferating tubular epithelium, which coincided with increased hepatocyte growth factor expression. In addition, Nlrp3KO tubular epithelial cells had an increased repair response in vitro, as seen by an increased ability of an epithelial monolayer to restore its structural integrity. In conclusion, Nlrp3 shows a tissue-specific role in which leukocyte-associated Nlrp3 is associated with tubular apoptosis, whereas renal-associated Nlrp3 impaired wound healing.Ischemia/reperfusion (IR) injury is a major cause of acute kidney injury¹ and increases the risk of developing chronic kidney disease (CKD).² After injury, wounded tissue organizes an efficient response that aims to combat infections, clear cell debris, re-establish cell number, and reorganize tissue architecture. First, necrotic tissue releases danger-associated molecular patterns, such as high-mobility group box-1³ or mitochondrial DNA,⁴ which leads to chemokine secretion⁵ and a subsequent influx of leukocytes. Second, neutrophils and macrophages clear cellular debris but also increase renal damage because depletion of neutrophils⁶ or macrophages within 48 hours of IR will reduce renal damage.⁷ At approximately 72 hours of reperfusion, the inflammatory phase transforms into the repair phase and is characterized by surviving tubular epithelial cells (TECs) that dedifferentiate, migrate, and proliferate to restore renal function.⁸Previously, we have shown that Toll-like receptor (TLR) 2 and TLR4 play a detrimental role after acute renal IR injury.^{9, 10, 11} In addition, TLR2 appeared also pivotal in mediating tubular repair in vitro after cisplatin-induced injury,¹² indicating a dual role for TLR2. The cytosolic innate immune receptor Nlrp3 is able to sense cellular damage¹³ and mediates renal inflammation and pathological characteristics after IR^{14, 15, 16} or nephrocalcinosis.¹⁷ Next to the detrimental role of Nlrp3 in different renal disease models and consistent with the dual role of TLR2, Nlrp3 was shown to protect against loss of colonic epithelial integrity.¹⁸ We, therefore, speculate that Nlrp3, which contributes to sterile renal inflammation during acute renal IR injury, might also drive subsequent tubular repair.To test this hypothesis, we investigated the role of leukocyte- versus renal-associated Nlrp3 with respect to tissue repair after renal IR. We observed that both renal- and leukocyte-associated Nlrp3s are detrimental to renal function after renal IR injury; however, this is through different mechanisms. Leukocyte-associated Nlrp3 is related to increased tubular epithelial apoptosis, whereas renal-associated Nlrp3 impairs the tubular epithelial repair response. Our data suggest Nlrp3 as a negative regulator of resident tubular cell proliferation in addition to its detrimental role in renal fibrosis and inflammation.^{14, 19}     

Design,content, and fieldwork procedures of the COVID‐19 Psychological Research Consortium (C19PRC) Study – Wave 4

ObjectivesThis paper outlines fieldwork procedures for Wave 4 of the COVID‐19 Psychological Research Consortium (C19PRC) Study in the UK during November–December 2020.MethodsRespondents provided data on socio‐political attitudes, beliefs, and behaviours, and mental health disorders (anxiety, depression, and posttraumatic stress). In Phase 1, adults (N = 2878) were reinvited to participate. At Phase 2, new recruitment: (i) replenished the longitudinal strand to account for attrition; and (ii) oversampled from the devolved UK nations to facilitate robust between‐country analyses for core study outcomes. Weights were calculated using a survey raking algorithm to ensure the longitudinal panel was representative of the baseline sample characteristics.ResultsIn Phase 1, 1796 adults were successfully recontacted and provided full interviews at Wave 4 (62.4% retention rate). In Phase 2, 292 new respondents were recruited to replenish the panel, as well as 1779 adults from Wales, Scotland, and Northern Ireland, who were representative of the socio‐political composition of the adult populations in these nations. The raking procedure successfully re‐balanced the longitudinal panel to within 1% of population estimates for selected socio‐demographic characteristics.ConclusionThe C19PRC Study offers a unique opportunity to facilitate and stimulate interdisciplinary research addressing important public health questions relating to the COVID‐19 pandemic.     

Sensory perception and motoric reactivity in Schizophrenic patients

Explored the effect of non-signal and signal stimuli conditions upon skin conductance (SC) and finger pulse amplitude (FPA) of 8 schizophrenic patients and 6 normal controls. Both groups were assessed on a reaction time (RT) task that consisted of visual, auditory and tactile stimuli. Schizophrenics were significantly slower in the perception and reaction to visual, auditory and tactile stimuli than the normal volunteers. The autonomic reactivity of schizophrenics and normals was nonsignificant during the relaxation and non-signal stimuli conditions. However, when schizophrenics were asked to respond to signal stimuli or when an interfering stimulus was introduced, an autonomic imbalance was observed. The concept of directional fractionation provides the theoretical framework for the discussion of the autonomic results.