Remote-controlled catheter ablation of accessory pathways: results from the magnetic laboratory.

AIMS: This study evaluates feasibility, safety, and efficacy of magnetic remote-controlled accessory pathway (AP) ablation. METHODS AND RESULTS: The novel magnetic navigation system (MNS) (Niobe, Stereotaxis) creates a steerable magnetic field (0.08 T) controlling the distal magnetic tip of an ablation catheter. In conjunction with a catheter advancer system (Cardiodrive, Stereotaxis) remote catheter ablation is enabled. Conventional electrophysiology study identified AP conduction in 59 patients (37 males, 36+/-14 years, 60 APs). First generation 1-magnet tip (1-M) (group I, n=18), second generation bipolar 3-magnet tip (3-M) (group II, n=27), and third generation quadripolar 3-magnet tip catheters (3-M quad.) (group III, n=14) were used for magnetic remote-controlled ablation. Successful AP ablation was achieved in 67% (group I), 85% (group II), and 92% (group III). A significant decrease of median [IQR: Q1-Q3] fluoroscopy time and dosage was observed: 21.2 [12.1-33.8] min, 1110 [395-3234] microGym2 (group I); 6.5 [4.4-15.4] min, 290 [129-489] microGym2 (group II), and 4.9 [3.4-8.0] min, 129 [74-270] microGym2 (group III). Mean procedure time (217+/-67 min; 182+/-68 min, and 172+/-90 min) significantly decreased in group III. Median number [Q1-Q3] of radiofrequency current applications in groups I, II, and III was 4 [2-9], 4 [2-6], and 2 [2-4], respectively. No complications occurred. CONCLUSION: Remote AP ablation is safe and feasible using the novel MNS. Introduction of the 3-magnet quadripolar ablation catheter significantly improved the efficacy of the procedure.     

Mechanisms of enhanced carbohydrate and lipid metabolism in adipose tissue in uremia.

OBJECTIVE: Hyperlipidemia is a permanent finding in advanced renal failure. It is supposed to be responsible for the accelerated arteriosclerosis and cardiovascular complications observed in patients with that disease. The background is partially determined, however, our knowledge in this matter is not yet satisfactory. METHODS: This study is based on the experimental rat model of chronic renal failure (CRF). Considering white adipose tissue (WAT) lipogenesis upregulation in CRF, along with the determination of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FAS) genes expression, we have measured WAT gene expression for sterol regulatory binding protein 1 (SREBP-1) at the level of protein mass and mRNA abundance. Furthermore, we have determined glucose uptake, glucose-to-CO 2 conversion rate, and glucose translocator (GLUT-4) gene expression in WAT. RESULTS: Upregulation of both FAS and ACC gene expression was found in WAT of CRF rats. It was accompanied by WAT SREBP-1 gene overexpression. Moreover, we have observed the increased glucose uptake, glucose to CO 2 conversion rate, and GLUT-4 gene expression in WAT of CRF rats in comparison with controls. CONCLUSION: SREBP-1 gene overexpression may contribute to enhanced lipogenesis upregulation in WAT of CRF rats. It is not excluded that the increased WAT glucose metabolism activity is also induced by this mechanism, although there is no evidence currently to that end. We hypothesize that the increased WAT lipogenesis capacity could be a part of mechanism(s) leading to CRF-induced hyperlipidemia.     

Fusion of bone marrow-derived stem cells with cardiomyocytes in a heterologous in vitro model.

OBJECTIVE: Recent studies have demonstrated that transplanted bone marrow-derived stem cells (BMCs) possess a broad differentiation potential and are able to form new cardiomyocytes. However, the identity of BMCs as true cardiomyocytes is still ambiguous. Therefore, we investigated the fate of transplanted fluorescence labeled BMCs and cardiomyocytes in co-culture. METHODS: For cell tracking we used two different fluorescent probes, Vybrant/DiO and Vybrant/DiI. BMCs were taken from human sternal marrow, purified using a Ficoll-gradient-centrifugation, treated with 5-azacytidine and stained with Vybrant/DiO. Furthermore, isolated spontaneous beating cardiomyocytes of neonatal rats (CM) were labeled with Vybrant/DiI. Thereafter, the BMCs were transplanted into CM-cultures and investigated on day 1, 4, 7, 14 and 28 using two-color fluorescence phenotyping by laser-scanning-cytometry (LSC). Two-color positive cells were harvested by patch-clamp technique and beta-MHC mRNA expression was analyzed by single-cell PCR. RESULTS: Two different morphological phenotypes were observed by LSC. First, isolated DiO labeled BMCs without contact or with direct cell contact to DiI labeled CMs. Second, some BMCs and CMs were double positive for DiO/DiI spontaneously forming hybrids. This population increased by 18% from day 1 to 4 and decreased only slightly until day 28. Additionally, few two-color positive cell formations expressed both human and rat specific beta-MHC mRNA as well as only human beta-MHC mRNA indicating that cell-fusion and transdifferentiation has occurred. CONCLUSION: These observations provide in vitro evidence for spontaneous cell fusion and transdifferentiation of BMCs in co-culture, raising the possibility that the observed phenomenons may contribute to development or maintenance of these cell types.     

Cognitive and neuroimaging predictors of instrumental activities of daily living.

Impaired ability to conduct daily activities is a diagnostic criterion for dementia and a determinant of healthcare services utilization and caregiver burden. What predicts decline in instrumental activities of daily living (IADLs) is not well understood. This study examined measures of episodic memory, executive function, and MRI brain volumes in relation to baseline IADLs and as predictors of rate of IADL change. Participants were 124 elderly persons with cognitive function between normal and moderate dementia both with and without significant small vessel cerebrovascular disease. Random effects modeling showed that baseline memory and executive function (EXEC) were associated with baseline IADL scores, but only EXEC was independently associated with rate of change in IADLs. Whereas hippocampal and cortical gray matter volumes were significantly associated with baseline IADL scores, only hippocampal volume was associated with IADL change. In a model including cognitive and neuroimaging predictors, only EXEC independently predicted rate of decline in IADL scores. These findings indicate that greater executive dysfunction at initial assessment is associated with more rapid decline in IADLs. Perhaps executive function is particularly important with respect to maintaining IADLs. Alternatively, executive dysfunction may be a sentinel event indicating widespread cortical involvement and poor prognosis.     

Effectiveness of early orthodontic treatment with the Twin-block appliance: a multicenter, randomized, controlled trial. Part 1: Dental and skeletal effects.

This study evaluated the effectiveness of early orthodontic treatment with the Twin-block appliance for the developing Class II Division 1 malocclusion. This multicenter trial was carried out in the United Kingdom. A total of 174 children, aged 8 to 10 years old, with Class II Division 1 malocclusion were randomly allocated to receive treatment with a Twin-block appliance or to an untreated, control group. Data were collected at the start of the study and 15 months later. Results showed that early treatment with Twin-block appliances resulted in reduction of overjet, correction of molar relationships, and reduction in severity of malocclusion. Most of this correction was due to dentoalveolar change, but some was due to favorable skeletal change. Early treatment with the Twin-block appliance is effective in reducing overjet and severity of malocclusion. The small change in the skeletal relationship might not be considered clinically significant.     

APOE epsilon3 gene transfer attenuates brain damage after experimental stroke.

Apolipoprotein E (apoE, protein; APOE, gene) is the major lipid-transport protein in the brain and plays an important role in modulating the outcome and regenerative processes after acute brain injury. The aim of the present study was to determine if gene transfer of the epsilon3 form of APOE improves outcome in a murine model of transient focal cerebral ischaemia. Mice received an intrastriatal injection of vehicle, a second-generation adenoviral vector containing the green fluorescent protein gene (Ad-GFP) or a vector containing the APOE epsilon3 gene (Ad-APOE) 3 days before 60 mins focal ischaemia. Green fluorescent protein expression was observed in cells throughout the striatum and subcortical white matter indicating successful gene transfer and expression. ApoE levels in the brain were significantly increased after Ad-APOE compared with Ad-GFP or vehicle treatment. Ad-APOE treatment reduced the volume of ischaemic damage by 50% compared with Ad-GFP or vehicle treatment (13+/-3 versus 29+/-4 versus 27+/-5 mm(3)). The extent of postischaemic apoE immunoreactivity was enhanced in Ad-APOE compared with Ad-GFP or vehicle treated mice. These results show the ability of APOE gene transfer to markedly improve outcome after cerebral ischaemia and suggest that modulating apoE levels may be a potential strategy in human stroke therapy.     

Improved sib-pair linkage test for disease susceptibility loci

An improved sib-pair test for linkage is introduced which is superior to the previously proposed tests. The test is derived from the standard chi-squared goodness of fit statistic by restricting the alternative hypothesis to the genetically possible. Critical values are given and exact power comparisons are made with the previously proposed tests. The new test is shown to be more powerful for finite samples as well as being asymptotically uniformly most powerful. © 1993 Wiley-Liss, Inc.     

Role of EDRF in the Regulation of Shear Rate in Large Coronary Arteries in Conscious Dogs

To determine whether dilation of large coronary arteries normalizes shear during increased flow following brief occlusion, six dogs were instrumented to measure aortic and left ventricular pressures, left circumflex coronary artery external diameter, and coronary blood flow. The coronary artery was occluded for 15 or 30 s. Data were obtained before and after blockade of EDRF synthesis with nitro-L-arginine. Internal coronary artery diameter and wall shear were calculated on a moment-to-moment basis and the area under the flow curve was measured. Peak flow and shear rate were unaffected by NLA or by the occlusion duration. Flow curve area increased with the duration of occlusion. Internal and external diameters increased significantly for 15 s occlusions before NLA (by 4 ± 1% in external diameter and by 11 ± 4% in internal diameter) and for 30 s occlusions before NLA (by 5 ± 1% in external diameter and by 14 ± 5% in internal diameter) but not after NLA. Adenosine infusions of 0.05, 0.10, 0.50, and 1.0 μmol/kg/min were also used to dilate the coronary arteries. With each infusion, flow, shear and diameter were allowed to reach steady state. Steady state shear was reduced only slightly and did not approach the baseline state. We conclude that increased shear rate causes an increase in coronary artery diameter which is EDRF dependent. Increased coronary artery diameter during reactive hyperemia and adenosine infusions did not normalize wall shear.     

Effect of Bendazac Lysine on lens and retina in diabetics

The possible beneficial effects on the lens and retina which Bendazac Lysine may have in the treatment of adult diabetic patients were investigated. Twenty patients, ranging in age from 54.80 ± 5.86 years old, were studied. The average duration of the diabetes was 11.32 ± 4.10 years. Thirteen patients had background retinopathy. The metabolic controls carried out during the study were satisfactory (HbA1<11%). Bendazac Lysine (500 mg three times a day) was administered for 6 months. Blood-retinal barrier permeability (VPR and VPRt) and lens transmittance (t) were evaluated prior to and 6 months after treatment by fluorophotometry. No statistically significant differences between the pre- and post-treatment values of the retina permeability were observed, however, there was a statistically significant improvement (p<0.05) (initial value: t= 0.813 ± 0.040 and final value: t=0.823 ± 0.037) in the lens transmittance. The authors conclude that Bendazac Lysine has a beneficial effect on the lens in the diabetic adult although no improvement in the permeability of the blood-retinal barrier has been observed.