Hepatitis C-associated autoimmunity in patients coinfected with HIV.

Background: Hepatitis C virus (HCV) infection is associated with multiple extrahepatic manifestations. It is unclear to what extent extrahepatic manifestations occur in HIV/HCV coinfection. Methods: We prospectively assessed cross-sectional frequencies of autoimmune manifestations in HIV/HCV-coinfected patients (n=98), HIV-mono-infected (n=45) and HCV-mono-infected patients (n=78). Diagnostic vasculitis scores, HCV and HIV loads, CD4 cell counts, thyroid-, cardiolipin-, non-organ-specific tissue antibodies (nuclear, smooth muscle, anti-liver-kidney-microsome, neutrophil-cytoplasmic) and cryoglobulins were determined. Results: Synergistic effects of HCV and HIV infection were observed with respect to the prevalence of antibodies against thyroglobulin (HCV infection 15.4%, HIV infection 8.8%, HIV/HCV coinfection 30.6%; P<0.001) and cardiolipin antibodies (HCV infection 9.0%, HIV infection 31%, HIV/HCV coinfection 46%; P<0.001). Cryoglobulinemia type III, was significantly associated with HCV infection (HCV, 25.6%; HIV/HCV, 20.4%) but not with HIV infection (4.4%, P<0.05). Rheumatoid factor was commonly detected in patients with HCV infection (48%), but occurred considerably less frequently in patients with HIV infection (4.4%) or HIV/HCV coinfection (9.5%, P<0.01). Conclusion: HIV coinfection appears to differentially modulate the frequency of HCV-related autoimmunity. However, autoimmunity is rarely accompanied by clinical manifestations.     

Increased distribution of collagen type III and reduced expression of matrix metalloproteinase 1 in patients with diverticular disease

Diverticular disease is an increasingly common clinical problem especially in Western industrialized countries, but the mechanism by which the disease develops remains unclear. Based on studies showing a structural change in the colonic wall in these patients, we examined whether there are any disorders concerning the collagen metabolism in patients with diverticular disease. Samples of colonic tissue from 13 patients with diverticulitis were compared to 14 controls. We performed a Sirius red test for the overall collagen content and immunohistochemical studies facing differentiation between collagen type I and type III and the expression of matrix metalloproteinases 1 and 13. In the bowel sections of patients with diverticulitis there were decreased levels of mature collagen type I (1.37+/- 0.32 vs. 1.59 +/- 0.31) and increased levels of collagen type III (1.61+/- 0.32 vs. 1.42 +/- 0.42), with a resulting lower collagen ratio I/III. The expression of MMP-I was reduced significantly in the diverticulitis group (4.83 +/- 0.92 vs. 6.02 +/- 1.98) while expression of MMP-13 did not differ significantly between the two groups (1.03 +/- 0.11 vs. 1.04 +/- 0.12). Our findings support the theory of structural changes in the colonic wall as one of the major pathogenic factors in the development of diverticular disease. Further studies must focus on the complex interactions of several extracellular matrix components.     

Inflammatory pseudotumor of the lung following invasive aspergillosis in a patient with chronic graft-vs.-host disease

Inflammatory myofibroblastic tumor (IMT) is an uncommon cause of solitary or multifocal lung nodules and can also be rarely found in various other extrapulmonary sites. Although this pseudotumor is benign, it can be locally very aggressive. The pathogenesis of IMT remains unclear; autoimmune or infectious origins have been hypothesized, so far. Here, we report a case of inflammatory pseudotumor of the lung secondary to invasive pulmonary aspergillosis in a patient with chronic graft-vs.-host disease. The 42-year-old patient presented with coughing and hemoptysis as major clinical signs 1 yr after successful HLA-identical stem cell transplantation. Aspergillus fumigatus was cultured from the bronchoscopic lavage, but intensive antifungal treatment could only initially improve the clinical situation. Diagnostic re-evaluation by open-chest biopsy surprisingly revealed an inflammatory pseudotumor responsible for clinical and radiographical deterioration. Both clinical and radiographical signs resolved under long-term steroids and secondary antifungal prophylaxis.     

Anticoagulation treatment for the reduction of stroke in atrial fibrillation: a cohort study to examine the gap between guidelines and routine medical practice

Background Atrial fibrillation (AF) is the most common heart arrhythmia, affecting 6% of people over 65 years, and carries a 4.5% average annual stroke risk, which can be reduced by appropriate anticoagulation. A multi-centre observational study, Management and Outcomes in the Care of Atrial fibrillation in Germany (MOCA) was conducted to evaluate the current anticoagulation treatment pattern in patients with AF in Germany. Methods Patients with AF were recruited from December 2003 to June 2004 in physician practices. Clinical data including International Normalised Ratio (INR) values and anticoagulation strategy were obtained from the physician chart and the patient follow-up, documenting hospitalisations, medications, and complications, was conducted at three and six months. Main outcome measures included anticoagulation methods, practice guidelines adherence and time within recommended anticoagulation range. Results 361 patients with AF (mean age 71±9, 61% male) were recruited in 45 physician practices. 90% of all patients had been treated with Vitamin K-Antagonists (VKA) at some time since AF-diagnosis, 88% were still treated. 10% of patients received aspirin as their anticoagulation therapy. Monitoring occurred at least once a month in over 70% of patients. Monitored INR values were 56% of the time within, 14% below and 30% over the recommended target range. A gap of 40% existed between the guideline recommendations and actual practice. Younger patients (<60 years of age) with no documented risk factors for stroke were over-treated with VKAs and patients older than 75 years without contraindications for anticoagulation were under-treated. Conclusions This study presents ‘real-life’ data in treating patients with AF in Germany and identifies the potential to advance the quality of care with respect to anticoagulation.     

Expression and Activity Patterns of Nitric Oxide Synthases and Antioxidant Enzymes Reveal a Substantial Heterogeneity Between Cardiac and Vascular Aging in the Rat

We investigated the effects of aging and ischemia–reperfusion (I/R) injury on the expression and activity of nitric oxide (^•NO) synthases and superoxide dismutase (SOD) isoforms. To this end we perfused excised hearts from young (6 months old) and old (31–34 months old) rats according to the Langendorff technique. The isolated hearts were, after baseline perfusion for 30 min, either subjected to 20 min of global no-flow ischemia followed by 40 min of reperfusion or were control-perfused (60 min normoxic perfusion). Both MnSOD and Cu,ZnSOD expression remained unchanged with increasing age and remained unaltered by I/R. However, SOD activity decreased from 7.55 ± 0.1 U/mg protein in young hearts to 5.94 ± 0.44 in old hearts (P<0.05). Furthermore, I/R led to a further decrease in enzyme activity (to 6.35 ± 0.41 U/mg protein; P<0.05) in myocardium of young, but not in that of old animals. No changes in myocardial protein-bound 3-nitrotyrosine levels could be detected. Endothelial NOS (eNOS) expression and activity remained unchanged in aged left ventricles, irrespective of I/R injury. This was in steep contrast to peripheral (renal and femoral) arteries obtained from the same animals where a marked age-associated increase of eNOS protein expression could be demonstrated. Inducible NOS expression was undetectable either in the peripheral arteries or in the left ventricle, irrespective of age. In particular when associated with an acute pathology, which is furthermore limited to a certain time frame, changes in the aged myocardium with respect to enzymes crucially involved in maintaining the redox homeostasis, seem to be much less pronounced or even absent compared to the vascular aging process. This may point to heterogeneity in the molecular regulation of the cardiovascular aging process.     

Comparison between pulsed and continuous radiofrequency delivery

INTRODUCTION: Potentials arising in the pulmonary veins (PV) have been proposed to be a trigger of atrial fibrillation. Percutaneously, the best results for curative treatment of atrial fibrillation have been achieved by segmental or circumferential isolation of the PV. The purpose of our study was to determine the feasibility of ostial pulmonary vein isolation and to compare continuous radiofrequency (RF) with pulsed RF concerning homogeneity and transmurality of produced lesions. MATERIALS AND METHODS: In vivo tests were performed in seven anesthetized and ventilated pigs. Under fluoroscopy and guided by intracardiac electrograms each of the 28 pulmonary veins was targeted for circumferential isolation near its ostium. After the continuous energy application in one PV-ostium the catheter was placed into the next PV-ostium and the same procedure was repeated using pulsed energy. The ablations were performed with an octapolar circumferential ablation catheter, with either continuous RF energy delivery to each electrode for 120 s or pulsed energy delivery to four electrodes simultaneously with a 5 ms duty cycle. Lesion diameter was measured with a microcaliper and homogeneity classified from 1 (highest) to 4 (least). RESULTS: More homogeneous lesions were produced in significantly less time with pulsed rather than with continuous energy delivery. There were no significant differences in impedance or temperature of the electrodes. We did not observe tissue carbonization or "popping," pulmonary vein stenosis, pericardial effusion/perforation at any time. CONCLUSION: Ostial ablation of the PV with pulsed energy delivery proved feasible. It was the faster and more reliable method of creating linear circumferential lesions with a maximum amount of homogeneity and transmurality. We observed no elevated risk of PV stenosis during our experiments.     

First use and limitations of Magmaris® bioresorbable stenting in a low birth weight infant with native aortic coarctation

We, herein, report the first use of a Magmaris® magnesium‐based vascular scaffold for native aortic coarctation in a 1,980 g infant with multiple malformations. Due to the low body weight, complex illness, and clinical instability, it was decided to delay surgical correction. After insufficient results had been obtained by balloon angioplasty, Magmaris® implantation was chosen to bridge the patient to surgery by stabilizing left ventricular function and to allow for sufficient growth. Due to significant early stent restenosis and complete loss of radial force, the patient required balloon reangioplasty only 21 days after Magmaris® implantation and early surgical correction. In addition, high systemic sirolimus levels were detected 48 hr after the intervention (5 ng/mL). Although the bioresorbable scaffold was successfully used as a short‐term bridge‐to‐surgery in our case, due to significant early stent failure (loss of radial force), this approach does not seem promising for long‐term bridging of infants with aortic coarctation. In addition, the consequences of sirolimus‐induced systemic immunosuppression may further limit the applicability of Magmaris® scaffolds in infants with congenital heart disease.     

Macrophage inflammatory protein 1-alpha (MIP-1 alpha ) triggers migration and signaling cascades mediating survival and proliferation in multiple myeloma (MM) cells

Recently, it has been demonstrated that macrophage inflammatory protein 1- alpha (MIP-1 alpha) is crucially involved in the development of osteolytic bone lesions in multiple myeloma (MM). The current study was designed to determine the direct effects of MIP-1 alpha on MM cells. Thus, we were able to demonstrate that MIP-1 alpha acts as a potent growth, survival, and chemotactic factor in MM cells. MIP-1 alpha-induced signaling involved activation of the AKT/protein kinase B (PKB) and the mitogen-activated protein kinase (MAPK) pathway. In addition, inhibition of AKT activation by phosphatidylinositol 3- kinase (PI3-K) inhibitors did not influence MAPK activation, suggesting that there is no cross talk between MIP-1 alpha-dependent activation of the PI3-K/AKT and extracellular-regulated kinase (ERK) pathway. Our data suggest that besides its role in development of osteolytic bone destruction, MIP-1 alpha also directly affects cell signaling pathways mediating growth, survival, and migration in MM cells and provide evidence that MIP-1 alpha might play a pivotal role in the pathogenesis of MM.     

Do Segmented Reconstruction Algorithms for Cardiac Multi-Slice Computed Tomography Improve Image Quality?

PURPOSE: To evaluate segmented reconstruction algorithms for spiral multi-slice computed tomography (MSCT) that use data from two cardiac cycles to improve temporal resolution (tau) for imaging of the heart. MATERIALS AND METHODS: An initial group of 78 cardiac patients (heart rates [HR] = 63-167 beats per minute [bpm]) were imaged on a 4-slice, 500 ms gantry rotation time scanner (scanner 1). Images were reconstructed with a single-segment algorithm using data from one cardiac cycle with a reconstruction window of fixed length (tau = 250 ms). Images were also reconstructed with two variants of a multi-segment algorithm using data from two cardiac cycles where only one end of the reconstruction window was fixed and the other end was freely moveable to allow adjustment of tau according to HR: (1) "2-segment fixed start" with fixed start of reconstruction, (2) "2-segment fixed end" with fixed end of reconstruction (for both, tau = 125-250 ms). The resulting image sets were ranked from best to worst (1-3, respectively) in a side-by-side, blinded comparison by two independent readers. A second group of 26 patients (HR = 74-90 bpm) were imaged on a 12-slice, 420 ms gantry rotation time scanner (scanner 2). Data were reconstructed with a single-segment algorithm (tau = 210 ms) and a "2-segment fixed start" algorithm (tau = 105-210 ms) and image sets were ranked from best to worst (1-2, respectively). RESULTS: There was no clear evidence that any one technique is superior for imaging on scanner 1. Reader 1 ranked single-segment images the highest for all HRs, but statistically significant differences among the three algorithms were only found for the lowest HRs (< 80 bpm), where reader 1 preferred single-segment over "2-segment fixed end" techniques (p = 0.048). The highest rankings given by reader 2 varied according to HR: single-segment images were superior for lowest HRs, while "2-segment fixed start" images were superior for HRs > 80 bpm; none of these comparisons reached statistical significance. Improved performance of 2-segment reconstruction was found with scanner 2. Both readers ranked "2-segment fixed start" images the highest (p < 0.01). CONCLUSIONS: The added value of 2-segment cardiac reconstruction algorithms for spiral MSCT was not demonstrated for a 4-slice, 500 ms gantry rotation time scanner but shown to be beneficial for a 12-slice, 420 ms gantry rotation time scanner in the crucial HR range of 74-90 bpm.