Treatment of in-stent restenosis with sirolimus-eluting-stents: results from the prospective German Cypher stent registry

Aims  Drug-eluting stents have been reported to effectively reduce in-stent restenosis (ISR). However, the effectiveness and safety have yet been investigated only in small trials or case series. The aim of this prospective large scale registry was to show that treatment of ISR with sirolimus eluting stents (SES) is safe, effective and feasible in daily routine. Methods and results  The German Cypher registry prospectively enrolled 6,555 patients undergoing implantation with SES for various indications, including 1,533 patients treated for ISR. Follow-up data (median 6.6 months) of this cohort was available for 1,531 patients (99.8%). Of these patients 75.8% were male. Of these patients 36.5% (n = 552) presented with acute coronary syndromes. In total, 1,932 SES were used with successful implantation in 98.9%. MI during hospitalization was observed in 0.7% (n = 11) while in-hospital mortality was only 0.1% (n = 2). MACE-rate at follow-up was 13.8% (n = 211) including a mortality of 1.3% (n = 20) and MI in 1.9% (n = 29). Total revascularization procedures including CABG (1.7%) were necessary in 12.3% (n = 186). Target vessel revascularization (TVR) rate was 9.3% (n = 139) and thus similar to patients with de novo lesions (8.1%, P = 0.69). Ten patients (0.65%) suffered from subacute stent thrombosis Vs. 0.24% observed in patients with de novo lesions (P = 0.03). Conclusion  This large registry confirms that treatment of ISR with sirolimus-eluting-stents is effective and save with good clinical results at index procedure and follow-up. TVR was not different from de novo lesions.     

Endothelial nitric oxide synthase and nitric oxide regulate endothelial tissue factor expression in vivo in the sickle transgenic mouse

Activation of the coagulation system is a characteristic feature of sickle cell anemia, which also includes clinical thrombosis. The sickle transgenic mouse abnormally expresses tissue factor (TF) on the pulmonary vein endothelium. Knowing that this aberrancy is stimulated by inflammation, we sought to determine whether nitric oxide (NO) contributes to regulation of endothelial TF expression in the sickle mouse model. We used the NY1DD sickle mouse, which exhibits a low‐TF to high‐TF phenotype switch on exposure to hypoxia/reoxygenation. Manipulations of NO biology, such as breathing NO or addition of arginine or L ‐NAME (N‐nitro‐L ‐arginine‐methyl‐ester) to the diet, caused significant modulations of TF expression. This was also seen in hBERK1 sickle mice, which have a different genetic background and already have high‐TF even at ambient air. Study of NY1DD animals bred to overexpress endothelial nitric oxide synthase (eNOS; eNOS‐Tg) or to have an eNOS knockout state (one eNOS^?/? animal and several eNOS^+/? animals) demonstrated that eNOS modulates endothelial TF expression in vivo by down‐regulating it. Thus, the biodeficiency of NO characteristic of patients with sickle cell anemia may heighten risk for activation of the coagulation system. Am. J. Hematol., 2010. © 2009 Wiley‐Liss, Inc.     

Detection and correction of endotracheal-tube position in premature neonates

Due to the short airways in premature children, an accurate position of the endotracheal tube (ETT) is crucial for adequate mechanical ventilation. Verification of ETT-position is done in chest radiographs. However, ETT-position varies substantially with head movement. When the head is flexed, the tube might appear too deeply inserted, and inadvertent extubation may occur in cases of retraction of ETT after radiography. Extension of the cervical spine will suggest an inappropriately high ETT-position, so that intended corrections can lead to main-stem intubation. Radiographic visible skeletal structures could serve as reference points to allow the detection of head declination and imperfect positioning of ETT. Ratios of anatomical landmarks were used to estimate head position.In this study, 111 radiographs of 24 preterm neonates with a gestational age of 24-29 weeks and weights of 500-1,000 g were analyzed. A mathematical algorithm for the detection and correction of ETT-positions, based on common chest radiographs, was developed. In 108 cases (97.3%), ETT-distance from the midtracheal level was less than 2 mm after use of the proposed correction.Thus, the suggested correction equation for head position enables verification of the actual ETT-position without requiring a defined placement of the head during radiography. Moreover, it can be helpful for estimating the depth of ETT-insertion in conditions when radiography is not available.     

MRSA-Infektionen des Bewegungsapparats

INTRODUCTION: We present gentamicin-vancomycin-impregnated beads that can be produced intraoperatively in moulds and demonstrated their successful use in ten cases of problematic Methicillin-resistant Staphylococcus aureus (MRSA) infection. METHODS: To produce the antibiotically loaded PMMA beads, a two-part mould of polyoxymethylene was used. The mixture of PMMA and antibiotic is poured into the mould halves, and during polymerisation the halves bond together. The in vivo antibiotic concentrations of wound secretion from the redon drainage were measured by fluorescence-polarisation immunoassay, and a concentration/time function was determined. The PMMA beads (2 g of vancomycin plus 0.5 g of gentamicin plus 40 g of PMMA) were implanted in ten patients aged 41-76 years. RESULTS: In all ten patients, the infection was cured (follow-up 15 months). CONCLUSION: The combination of gentamicin and vancomycin in the PMMA of standardised beads represents a good alternative in the treatment of MRSA infections. Understanding of the mechanism of antibiotic release from PMMA allows differentiated dosing during systemic application.     

A bronchogenic cyst of the right ventricular endocardium

In a 73-year-old male patient with a history of prostate cancer, a right ventricular endoluminal tumor was diagnosed by echocardiography. An endocardial papillary fibroelastoma or myxoma appeared possible; a malignant tumor could not be ruled out. The tumor was resected using extracorporeal circulation and cardioplegic arrest. Histopathology study revealed a bronchogenic cyst with ciliated epithelium.     

The antifibrotic effects of relaxin in human renal fibroblasts are mediated in part by inhibition of the Smad2 pathway

BACKGROUND: The peptide hormone relaxin has been demonstrated to exert antifibrotic effects in renal and extrarenal tissues. The aims of this study were to identify potential anti-fibrotic effects of relaxin on human renal fibroblasts in vitro and to analyze their mechanisms. METHODS: All experiments were performed in established renal fibroblast cell lines and in primary cortical fibroblasts. Effects of relaxin were analyzed on cell proliferation, apoptosis, activation of renal fibroblasts, synthesis and secretion of collagen type I and fibronectin, as well as on the secretion of matrix metalloproteinases (MMPs). Effects on transforming growth factor-beta1 (TGF-beta1) receptor binding were analyzed by flow cytometry and on TGF-beta1 signal transduction by immunoblot analyses for Smad4 and 7, translocation from cytosol to nucleus for Smad2 and 3 as well as for phosphorylated and unphosphorylated forms of p38, c-Jun NH2 terminal kinase (JNK) and extracellular-regulated protein kinase (ERK). Finally, specific siRNAs for Smad2 and 3 were applied to assess the signal transduction pathway. RESULTS: After stimulation with relaxin, tyrosine phosphorylation of a 220 kD protein was demonstrated, indicating interaction with the receptor. Relaxin had only modest inhibitory effects on cell proliferation, and no effects on apoptosis. Conversely, relaxin exerted robust effects on TGF-beta1-induced fibroblast to myofibroblast transformation as well as on matrix synthesis and secretion even at the smallest dose tested. The secretion of MMP-2 and MMP-9 was induced noticeably by all investigated relaxin concentrations. TGF-beta1 receptor binding was not influenced by relaxin; however, it prevented Smad2 phosphorylation, translocation to nucleus, and complex formation between Smad2 and 3 indicating a possible interaction with TGF-beta1 signaling. These findings were corroborated by studies using siRNAs to Smad2 and 3 where siRNA to Smad2 but not to Smad3 inhibited the TGF-beta1 induction of fibronectin synthesis. There was no influence of relaxin on intracellular Smad3, Smad4, and Smad7 translocation or phosphorylation of mitogen-activated protein (MAP) kinases. CONCLUSION: Relaxin is a potent inhibitor of TGF-beta1-induced extracellular matrix (ECM) synthesis and secretion as well as fibroblast activation. Furthermore, it induces ECM degradation by induction of MMP-2 and MMP-9. These effects are mediated, at least in part, by inhibition of TGF-beta1 signaling.     

Simple decompression or subcutaneous anterior transposition of the ulnar nerve for cubital tunnel syndrome

The purpose of this prospective randomised study was to evaluate which operative technique for treatment of cubital tunnel syndrome is preferable: subcutaneous anterior transposition or nerve decompression without transposition. This study included 66 patients suffering from pain and/or neurological deficits with clinically and electromyographically proven cubital tunnel syndrome. Thirty-two patients underwent nerve decompression without transposition and 34 underwent subcutaneous transposition of the nerve. Follow-up examinations evaluating pain, motor and sensory deficits as well as motor nerve conduction velocities, were performed 3 and 9 months postoperatively. There were no significant differences between the outcomes of the two groups at either postoperative follow-up examination. We recommend simple decompression of the nerve in cases without deformity of the elbow, as this is the less invasive operative procedure.