Right ventricular pacing is an independent predictor for ventricular tachycardia/ventricular fibrillation occurrence and heart failure events in patients with an implantable cardioverter-defibrillator

Aims: There is increasing evidence that right ventricular (RV) pacingmay have detrimental effects by increasing morbidity and mortalityfor heart failure in implantable cardioverter–defibrillator(ICD) patients. In this study we prospectively tested the hypothesisthat cumulative RV pacing increases ventricular tachycardia/ventricularfibrillation (VT/VF) occurrence (primary endpoint) and hospitalizationand mortality for heart failure (secondary endpoint) in a predominantlysecondary prophylactic ICD patient population. Methods and results: Two hundred and fifty patients were divided into two groupsaccording to the median of cumulative RV pacing (2 vs. >2%)and prospectively followed-up for occurrence of primary andsecondary endpoints for 18 ± 4 months. Established predictorsfor VT/VF occurrence and heart failure events such as age, leftventricular ejection fraction (EF), QRS duration, history ofatrial fibrillation, and NT-proBNP were collected at enrolment.Multivariate Cox regression analysis revealed that cumulativeRV pacing > 2% and EF < 40% were independent predictorsfor VT/VF occurrence and heart failure events. Kaplan–Meieranalysis showed that patients with >2% cumulative RV pacingmore frequently suffered from VT/VF occurrence and heart failurehospitalization. Conclusion: Cumulative RV pacing > 2% and EF < 40% are independentpredictors for VT/VF occurrence and mortality and hospitalizationfor heart failure in predominantly secondary prophylactic ICDpatients. Our data show that algorithms capable of reducingcumulative RV pacing should be used more frequently in clinicalpractice.     

Prediction of clinical outcomes in Crohn’s disease by using confocal laser endomicroscopy: results from a prospective multicenter study

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Reappraisal of the clinical and etiologic significance of immunoglobulin deviations in autoimmune hemolytic anemia (‘warm type’)

Summary 56 patients with autoimmune hemolytic anemia (warm type) (AIHA) were investigated for immunoglobulin deviations. Of these, 43 were repeatedly analyzed (mean 4 times). The mean observation time was 20 months. The immunoglobulin values were correlated with clinical (degree of hemolysis) and serological (immunoglobulin class of autoantibodies; strength of antiglobulin reaction) parameters and statistically evaluated by variance analysis. Although no significant deviations of immunoglobulins in AIHA were found as compared to a normal control group, the immuno-globulin disturbance most frequently seen was an elevation of IgM. This is inter-preted as a possible lack or functional impairment of immunoregulatory T cells in AIHA.Supported by the Deutsche Forschungsgemeinschaft (Mu 277/6).     

Differential expression of connective tissue growth factor in inflammatory bowel disease

Inflammatory bowel disease consists of Crohn's disease (CD) and ulcerative colitis (UC). A major clinical problem in some patients is to differentiate clearly between these entities, which is important when planning appropriate medical and surgical treatment. Connective tissue growth factor (CTGF), a novel peptide involved in fibrotic disorders, was analyzed in the present study in CD and UC patients to evaluate its possible role in these two disorders. Twenty-five normal human intestinal tissue samples were obtained through an organ donor program. CD tissues were obtained from 28 individuals undergoing partial intestinal resection (17 small bowel; 11 large bowel) due to complications of the disease. UC tissue samples were obtained from 16 patients undergoing colectomy due to complications of the disease. Expression of CTGF was studied by Northern blot analysis. In situ hybridization was used to localize mRNA moieties in the tissue samples. Northern blot analysis revealed an average 5-fold increase in CTGF mRNA expression in 89% (25/28) of CD tissue samples by comparison with normal controls (p < 0.0001). In contrast, in UC samples CTGF mRNA levels were comparable to those of normal controls. However, UC tissue samples exhibited enhanced TGF-beta1 mRNA levels (4-fold; p < 0.05). In situ hybridization in CD samples showed CTGF mRNA localized especially in fibroblasts within the submucosal layer, around lymph follicles and in some areas of intense damage in the proximity of the luminal surface, whereas inflammatory cells were devoid of any CTGF mRNA signal. The present data indicate that CTGF plays a different role in IBD and might be useful, especially in those cases with unusual disease presentation, to better differentiate UC and CD. In addition, our data indicate a crucial role for CTGF in CD, where fibrosis and stenosis are frequent complications that require surgery.     

A common founder mutation in FANCA underlies the world's highest prevalence of Fanconi anemia in Gypsy families from Spain

Fanconi anemia (FA) is a genetic disease characterized by bone marrow failure and cancer predisposition. Here we have identified Spanish Gypsies as the ethnic group with the world's highest prevalence of FA (carrier frequency of 1/64-1/70). DNA sequencing of the FANCA gene in 8 unrelated Spanish Gypsy FA families after retroviral subtyping revealed a homozygous FANCA mutation (295C>T) leading to FANCA truncation and FA pathway disruption. This mutation appeared specific for Spanish Gypsies as it is not found in other Gypsy patients with FA from Hungary, Germany, Slovakia, and Ireland. Haplotype analysis showed that Spanish Gypsy patients all share the same haplotype. Our data thus suggest that the high incidence of FA among Spanish Gypsies is due to an ancestral founder mutation in FANCA that originated in Spain less than 600 years ago. The high carrier frequency makes the Spanish Gypsies a population model to study FA heterozygote mutations in cancer.     

The endophytic fungus Piriformospora indica reprograms barley to salt-stress tolerance, disease resistance, and higher yield

Disease resistance strategies are powerful approaches to sustainable agriculture because they reduce chemical input into the environment. Recently, Piriformospora indica, a plant-root-colonizing basidiomycete fungus, has been discovered in the Indian Thar desert and was shown to provide strong growth-promoting activity during its symbiosis with a broad spectrum of plants. Here, we report on the potential of P. indica to induce resistance to fungal diseases and tolerance to salt stress in the monocotyledonous plant barley. The beneficial effect on the defense status is detected in distal leaves, demonstrating a systemic induction of resistance by a root-endophytic fungus. The systemically altered "defense readiness" is associated with an elevated antioxidative capacity due to an activation of the glutathione-ascorbate cycle and results in an overall increase in grain yield. Because P. indica can be easily propagated in the absence of a host plant, we conclude that the fungus could be exploited to increase disease resistance and yield in crop plants.     

Huntington's Disease (HD): Neurodegeneration of Brodmann's Primary Visual Area 17 (BA17)

Huntington's disease (HD), an autosomal dominantly inherited polyglutamine or CAG repeat disease along with somatomotor, oculomotor, psychiatric and cognitive symptoms, presents clinically with impairments of elementary and complex visual functions as well as altered visual‐evoked potentials (VEPs). Previous volumetric and pathoanatomical post‐mortem investigations pointed to an involvement of Brodmann's primary visual area 17 (BA17) in HD. Because the involvement of BA17 could be interpreted as an early onset brain neurodegeneration, we further characterized this potential primary cortical site of HD‐related neurodegeneration neuropathologically and performed an unbiased estimation of the absolute nerve cell number in thick gallocyanin‐stained frontoparallel tissue sections through the striate area of seven control individuals and seven HD patients using Cavalieri's principle for volume and the optical disector for nerve and glial cell density estimations. This investigation showed a reduction of the estimated absolute nerve cell number of BA17 in the HD patients (71 044 037 ± 12 740 515 nerve cells) of 32% in comparison with the control individuals (104 075 067 ± 9 424 491 nerve cells) (Mann–Whitney U‐test; P < 0.001). Additional pathoanatomical studies showed that nerve cell loss was most prominent in the outer pyramidal layer III, the inner granular layers IVa and IVc as well as in the multiform layer VI of BA17 of the HD patients. Our neuropathological results in BA17 confirm and extend previous post‐mortem, biochemical and in vivo neuroradiological HD findings and offer suitable explanations for the elementary and complex visual dysfunctions, as well as for the altered VEP observed in HD patients.     

Self-expandable metallic stents for malignant duodenal obstruction caused by biliary tract cancer

BACKGROUND: Malignant duodenal obstruction is a common event in patients with advanced biliary tract cancer. Because bypass surgery is accompanied by significant morbidity, self-expandable metallic stents have emerged as a possible alternative for palliation. METHODS: Twenty patients with biliary tract cancer (7 gallbladder, 13 Klatskin tumors) and duodenal obstruction were treated with metallic stents at a single institution between 1999 and 2001. Survival, morbidity, and stent function were studied prospectively. The ability to eat was assessed by using a scoring system. RESULTS: Stent placement was technically successful in all patients. An additional stent was required in 6 cases (4 occlusions, 2 dislocations). Median survival was 20.5 weeks; there was no treatment-related death. Twenty-eight biliary stent exchanges were performed in 13 (65%) patients. Erosive reflux esophagitis improved in 11 of 12 (92%) cases. After 4 weeks, all 17 surviving patients tolerated soft or solid food, whereas 13 of 17 (77%) tolerated a more solid diet (p < 0.001, gastric outlet obstruction scoring system). Twelve of 17 (71%) patients gained a median of 1.5 kg of body weight (p = 0.001). The median Karnofsky scale increased from 50% to 60% in 13 of 17 (77%) patients. CONCLUSIONS: Self-expandable metallic stents are a safe, efficacious, and minimally invasive treatment option for palliation of patients with duodenal obstruction from biliary tract cancer. Technical complications can be managed endoscopically and the bile duct remains accessible for endoluminal treatment.