Impact of ramipril versus other angiotensin-converting enzyme inhibitors on outcome of unselected patients with ST-elevation acute myocardial infarction

We examined the impact of treatment with ramipril versus other angiotensin-converting enzyme (ACE) inhibitors on clinical outcome in unselected patients of the prospective multicenter registry Maximal Individual Therapy of Acute Myocardial Infarction PLUS registry (MITRA PLUS). Of 14,608 consecutive patients with ST-elevation acute myocardial infarction, 4.7% received acute therapy with ramipril, 39.0% received other ACE inhibitor therapy, and 56.3% received no ACE inhibitor therapy. In a multivariate analysis, the treatment with ramipril compared with the treatment without ACE inhibitors was associated with a significantly lower hospital mortality and a lower rate of nonfatal major adverse coronary and cerebrovascular events. Compared with other generic ACE inhibitors, ramipril therapy was independently associated with a significantly lower hospital mortality (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.32 to 0.90) and a lower rate of nonfatal major adverse coronary and cerebrovascular events (OR 0.65, 95% CI 0.46 to 0.93), but not with a lower rate of heart failure at discharge (OR 0.79, 95% CI 0.50 to 1.27).     

Expression profile of the telomeric complex discriminates between benign and malignant pheochromocytoma

Telomerase, a ribonucleoprotein complex that includes the telomerase RNA component, the telomerase-associated protein (TP1), the telomerase catalytic subunit (hTERT), and the heat shock protein 90 (HSP90), is closely related to the malignant potential of human tumors. In pheochromocytomas (PC) it is very difficult to predict malignant potential by conventional histology or immunohistochemical and molecular markers. To test whether the expression of telomerase subunits is reflected in the malignant transition of PCs, we determined their mRNA and/or protein expression in 28 benign and nine malignant PCs and compared the results with telomerase activity. RT-PCR analysis revealed that TP1 was ubiquitously expressed. The telomerase RNA component was found in all malignant (100%) and in 13 of 28 (46%) benign PCs. In contrast, hTERT was clearly associated with aggressive biological behavior. All of the malignant (100%), but only two of 28 benign (7%) PCs expressed hTERT. HSP90 was increased in malignant PCs, but was also expressed at a lower level in benign tumors. High telomerase activity was measurable in hTERT-positive tissues only. Our data indicate that hTERT, HSP90, and telomerase activity are up-regulated in malignant cells of the adrenal medulla. The common expression of hTERT and telomerase activity thus represents an additional prognostic marker that may identify more aggressive tumors.     

Die dorsoposteriore extraperitoneale Pelviskopie (DEP) Rektum erhaltende mesorektale Resektion beim T1-High-Risk-Rektumkarzinom

Zusammenfassung Hintergrund: Die lokale Rektum erhaltende Resektion des Low-Risk-T1-Rektumkarzinoms ist heute ein als Standard akzeptiertes Verfahren. Bei den High-Risk-T1-Tumoren ist bei nicht bekanntem Lymphknotenstatus eine Rektumresektion zu fordern. Mit der dorsoposterioren extraperitonealen Pelviskopie (DEP) wurde eine Methode entwickelt, mit der das Mesorektum in minimalinvasiver Technik unter Erhaltung des Rektums reseziert werden kann, um so auch das nodale Stadium zu diagnostizieren. Patienten und Methodik: Bei bisher zehn Patienten mit High-Risk-T1-Rektumkarzinom wurde nach transanaler R0-Resektion und konventionellem Staging mit CT, Abdomensonographie und transanaler Sonographie in der Regel zweizeitig eine DEP durchgeführt. Die Eingriffe erfolgten in Allgemeinnarkose in Bauchhängelage (Götze-Lagerung). Das Spatium retrorectale wurde mit einem Dilatationsballonsystem von perineal aufgedehnt, ein Pneumoextraperitoneum angelegt und das Mesorektum über drei Ports reseziert. Ergebnisse: Es gelang problemlos und unter Sicht, das Spatium retrorectale zu dilatieren. Der entstandene Arbeitsraum konnte unter hervorragenden Sichtverhältnissen bis zum Promontorium sacri erweitert werden. Das Mesorektum wurde im Sinne einer Staging-Operation vollständig reseziert. Bei der histologische Aufarbeitung der Resektate fanden sich zwischen vier und 20 Lymphknoten. Bei einer Patientin bestand histologisch eine Mikrometastasierung. Im Verlauf zeigte sich bei dem einmalig durchgeführten, einzeitigen Vorgehen eine Wundheilungsstörung im Bereich der Vollwandexzision mit Ausbildung einer rektrovaginalen Fistel. Bei einer weiteren Patientin fanden sich bei der 6 Wochen postoperativ durchgeführten Analmanometrie Zeichen einer Inertia recti. Schlussfolgerung: Mit keiner diagnostischen Maßnahme außer der Histologie lassen sich befallene Lymphknoten ausschließen oder beweisen. Bei der mesorektalen Resektion mittels DEP ist ein adäquates Lymphknoten-Staging erzielbar. Das Rektum erhaltende Vorgehen kann auch auf die Gruppe der High-Risk-T1-Rektumkarzinomen ausgedehnt werden und eine differenziertere Therapieplanung ermöglichen. Abstract Background: Local resection of low-risk T1 carcinoma of the rectum is an accepted standard of treatment. In high-risk T1 tumors a standard resection should be considered due to the possibility of lymph node metastasis. The dorso-posterior extraperitoneal pelviscopy (DEP) is a method to explore and dissect the mesorectum as a staging procedure. Patients and Methods: We describe the results of ten patients with high-risk T1 rectal cancer in whom, following transanal R0 resection and conventional staging (CT scan, transanal endosonography and abdominal sonography) DEP was performed. The operation was carried out in general anesthesia, the patient in prone jack-knife position. The retrorectal space was dilated with a balloon through a dorso-posterior approach. The extraperitoneal pelvic structures were dissected with a three-port technique and CO₂ insufflation. Results: The procedures were performed without technical difficulty. With this method we could extract between four and 20 lymph nodes. In one patient micrometastases where detected. In the only one-stage procedure the patient developed an insufficiency of the transanal suture and a rectovaginal fistula. In a second patient we found an inertia recti 6 weeks postoperatively. Conclusion: A positive lymph node stage can only be diagnosed histologically. DEP is a method that aspires to achieve histological lymph node staging following local resection of high-risk T1 tumors, so that rectum-sparing treatment can be supported. Indications for rectum-sparing surgery could possibly also be extended to high-risk T1 tumors with this method.     

Myeloablative intensified conditioning regimen with in vivo T-cell depletion (ATG) followed by allografting in patients with advanced multiple myeloma. A phase I/II study of the German Study-group Multiple Myeloma (DSMM)

We investigated toxicity and efficacy of in vivo T-cell depletion with anti-thymocyte globulin (ATG) as part of an intensified myeloablative conditioning regimen followed by allogeneic stem cell transplantation in patients with advanced multiple myeloma. The conditioning regimen consisted of modified total body irradiation, busulfan and cyclophosphamide (n=15) or in the case of prior dose-limiting radiotherapy of busulfan and cyclophosphamide (n=3). The median age was 44 years (range, 29-53) and the median time from diagnosis to transplant was 12 months (range, 6-144). Grade II-IV acute graft-versus-host disease (GvHD) occurred in six patients (35%). Severe grade III/IV GvHD developed in one patient (6%). Three patients died of therapy-related causes (17%). A complete remission (CR) with negative immunofixation after allogeneic transplantation was seen in eight of the evaluable patients (53%). After a median follow-up of 41 months (range, 8-84), the estimated overall survival at 6 years for all patients is 77% (CI 95%: 58-96%). The estimated progression-free survival at 6 years for all patients is 31% (CI 95%: 2-59%) and 46% (CI 95%: 9-83%) for patients with CR. In vivo T-cell depletion with ATG resulted in a low rate of severe GvHD with low treatment-related mortality, and a substantial number of long-term survivors.     

Intra- and intermodal integration of discrepant visual and proprioceptive action effects

Integration of discrepant visual and proprioceptive action effects puts high demands on the human information processing system. The present study aimed to examine the integration mechanisms for the motor (Exp. 1) and visual modality (Exp. 2). According to theories of common coding, we assumed that visual as well as proprioceptive information is represented within the same cognitive domain and is therefore likely to affect each other (multisensory cross talk). Thus, apart from the often-confirmed visual dominance in multisensory integration, we asked about intra- and intermodal recall of either proprioceptive or visual information and whether there were any differences between the motor and visual modality. In a replication paradigm, we perturbed the relation between hand movements and cursor movements. The task required the (intra- vs. intermodal) replication of an initially performed (seen) hand (cursor) movement in a subsequent motor (visual) replication phase. First, mechanisms of integration were found to be dependent on the output modality. Visual action effects interfered the motor modality, but proprioceptive action effects did not have any effects on the visual modality. Second, however, intermodal integration was more susceptible to interference, and this was found to be independent from the output modality. Third, for the motor modality, the locus of perturbation (perturbation of cursor amplitude or perturbation of hand amplitude) was irrelevant, but for the visual modality, perturbation of hand amplitudes reduced the cross talk. Tool use is one field of application of these kinds of results, since the optimized integration of conflicting action effects is a precondition for using tools successfully.     

The simultaneous occurrence of human norovirus and hepatitis E virus in a Norway rat (Rattus norvegicus)

Wild rats can be reservoirs and vectors for several human pathogens. An initial RT-PCR screening of the intestinal contents of Norway rats trapped in the sewer system of Copenhagen, Denmark, for caliciviruses revealed the presence of a human norovirus in one of 11 rodents. Subsequent phylogenetic analysis of the ~4.0-kb 3′-terminus of the norovirus genome resulted in the identification of a recombinant GI.b/GI.6 strain. The simultaneous detection of hepatitis E virus-like particles in the feces of this rat by transmission electron microscopy was confirmed by RT-PCR and sequence determination, resulting in the identification of a novel rat hepatitis E virus.     

β3-integrin Leu33Pro gain of function variant does not modulate inflammatory activity in human derived macrophages in diabetes

Objective: We aimed to investigate the association between the Leu33Pro (rs5918) polymorphism in β3-integrin with diabetic complications and inflammatory function of macrophages depending on the genotype in subjects with diabetes mellitus.Material and methods: We determined the Leu33Pro polymorphism in 186 diabetic subjects and collected laboratory data. Monocytes from 24 patients were collected for macrophage differentiation to determine the inflammatory activity by treating with different stimulants.Results: We could demonstrate that human derived differentiated macrophages expressed β3‑integrin. Their secretory capacity upon inflammatory stimulation did not reveal any differences depending on the Leu33Pro variant. We found trends for an association of the polymorphism with the presence of diabetic nephropathy (p = 0.071), as well as with creatinine [1.32 mg/dL (1) vs. 0.98 mg/dL (0)] (p = 0.029 in recessive model) and glomerular filtration rate [75.6 ml/min ± 22 vs. 62.3 ml/min ± 25] (p = 0.076 in recessive model) as quantitative markers of kidney function.Conclusion: Despite the expression of β3‑integrin in human macrophages, the Leu33Pro polymorphism in β3‑integrin does not modify the inflammatory response upon stimulation but might play a role in the progression of diabetic nephropathy. Further studies are necessary to substantiate such a hypothesis.