Predictors of colonization with Staphylococcus species among patients scheduled for cardiac and orthopedic interventions at tertiary care hospitals in north-eastern Germany-a prevalence screening study.

As methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection in humans are a global challenge. In Mecklenburg and Western Pomerania (Germany) 1,517 patients who underwent surgical interventions were systematically screened for MRSA and MSSA colonization on the day of hospital admission and discharge. Demographic data, risk factors and colonization status of the (i) nose, (ii) throat, (iii) groin, and (iv) thorax or site of surgical intervention were determined. Of the 1,433 patients who were included for further evaluation, 331 (23.1%) were colonized with MSSA, while only 17 (1.2%) were MRSA carriers on the day of hospital admission. A combination of nose, throat and groin swabs returned a detection rate of 98.3% for MSSA/MRSA. Trauma patients had lower prevalence of MRSA/MSSA (OR 0.524, 95% CI: 0.37-0.75; p < 0.001) than patients with intended orthopedic interventions. Males showed significantly higher nasal S. aureus carrier rates than females (odds ratio (OR) = 1.478; 95% CI: 1.14-1.92; p = 0.003). Nasal S. aureus colonization was less frequent among male smokers as compared to non-smokers (chi2 = 16.801; phi = 0.154; p < 0.001). Age, gender and smoking had a significant influence on S. aureus colonization. Combining at least three different swabbing sites should be considered for standard screening procedure to determine S. aureus colonization at patients scheduled for cardiac or orthopedic interventions at tertiary care hospitals.

Adjunctive surgical atrial fibrillation ablation during cardiac surgery: real life experiences.

AIM: Several tools have been invented for surgical atrial fibrillation (AF) ablation. In this study, we investigated the real world efficacy of intraoperative AF ablation (AFA) with radiofrequency-energy or cryo-ablation and performed an electro-anatomical remap in some patients with recurrences. METHODS: Seventy-three consecutive patients (53 male, median age of 69 ± 7 years) with history of AF underwent cardiac surgery for valve repair (74 % mitral defects, 60 % aortic defects) and/or coronary artery bypass graft procedures (56 %). During a follow-up of 23 ± 11 months after AFA we performed intensified holter-monitoring (4-7 days). Patients with symptomatic relapse of atrial arrhythmias (AA) were offered the opportunity for additional electrophysiological examination (EPE). RESULTS: During 23 ± 11 months after AFA, 45 patients (62 %) had recurrent AA. In eight patients we performed EPE. In all 8 cases, septal circumferential lesions could be demonstrated during mapping with discrete gaps. All lateral veins were isolated however, posteriorly deep inside the vein leaving the antral region completely untreated. Neither roof lines nor mitral isthmus lines were complete. Performing catheter ablation, all veins could be isolated and seven patients were free of any arrhythmias during follow up (9 ± 5 months) without taking antiarrhythmic drugs. CONCLUSION: Surgical AF ablation may often be incomplete rendering sobering results in unselected patients. Completion of the ablation is feasible with catheter ablation with good clinical outcome.

Characterization of ion currents of murine CD117(pos) stem cells in vitro and their modulation under AT2 R stimulation.

AIM: Hematopoietic stem cells, especially CD117(pos) cells, have been found to possess a regenerative potential in various tissues, in particular cardiac muscle. However, the characterization of the relevant ion currents of stem cells prior to implantation lacks documentation. Activation of angiotensin II type 2 receptor (AT2 R) can lead to further cell differentiation and receptor auto-expression and might thus influence electrophysiological properties of CD117(pos) stem cells. This study was designed to functionally characterize membrane currents of CD117(pos) cells under normal and AT2 R-stimulated conditions. METHODS: CD117(pos) murine bone marrow stem cells were isolated with MACS technique and stimulated for the AT2 R with angiotensin II and losartan for 3-5 days prior to patch-clamp measurements. RT-PCR was used to determine channel expression. Endothelial properties were analysed with immunocytochemistry and acLDL uptake assay. RESULTS: A well-expressed inward rectifying current (IKir ) was identified in cultured CD117(pos) cells. Furthermore, a ZD 7288 (HCN channel blocker)-sensitive current component was isolated. Voltage-dependent potassium currents and chloride currents were less expressed. A small fraction of cells demonstrated voltage- and time-dependent inward currents. In AT2 R-stimulated cells inward rectifying the hyperpolarization-induced inward currents were slightly attenuated on the translational level but showed increased mRNA expression. Cultured CD117(pos) cells express CD31 and VEGFR-2 and significantly increased the uptake of acLDL. CONCLUSIONS: CD117(pos) cells do not have properties of action potential-generating cells and moderately change their excitability during AT2 R stimulation. Electrophysiological and molecular properties of control and AT2 R-stimulated cells point to a differentiation to vascular endothelial cells. This could increase beneficial vascularization in injured tissues.

Cell-free collagen-based scaffolds used for making blood vessels in cardiovascular surgery.

The present article deals with the technology of obtaining decellularized cell-free collagen-based scaffolds from arterial vessels and surgical assessment of the possibility of experimentally implanting them into the blood system of laboratory animals for experimental purposes. The study was performed on arterial vessels (n=60) and fragments of the human internal thoracic artery (n=20). Described herein is a method of obtaining a connective-tissue matrix of a blood vessel by means of vessel's perfusion for 2-3 hours with detergent solutions. Cell-free collagen-based conduits were implanted to a total of ten dogs. After the operation, the blood flow remained functional. The anastomoses established turned out to be leak-proof and the acellular vessels were able to withstand the haemodynamic load of the arterial blood flow.

Tissue-engineered devices in cardiovascular surgery.

Manufacturing life-long functional cardiovascular (CV) implants is the ultimate goal for researchers and clinicians in the cardiothoracic field. Tissue engineering (TE) is an opportunity to create ideal prostheses that are vital, growing, adaptive, autologous and functionally optimally performing. Today, initial translation from basic science to first clinical trials has begun. The article depicts the state of the art in TE techniques for CV products and describes milestones in the ongoing development of tissue-engineered myocardial, valvular and vascular devices from an experimental and clinical point of view. Artificial CV implants still reveal remarkable limitations but promising advances regarding optimal structural design, the prevention of intimal hyperplasia and the reduction of antigenicity and thrombogenicity. Where applicable, the implantation of vascularized autografts should still be preferred. Apart from that, decellularized allogen bioprostheses currently represent most promising matrix scaffolds that can be autologously cellularized in vitro prior to or in vivo after implantation. Capable biologic alternatives have been described like the decellularized porcine small intestinal submucosa. Rising evidence suggests that in vitro endothelialization might be the minimal requirement for improved long-term results of biological tissue-engineered CV grafts.

[Cell sources for cardiovascular tissue engineering]. / Zellquellen für kardiovaskuläres Tissue Engineering.

Numerous studies have confirmed that stem cell therapy has significant potential for the regeneration of congenital and acquired heart diseases. The utilization of embryonic stem cells and induced pluripotent stem cells promises a possible generation and regeneration of all cardiovascular structures. On the one hand fetal and adult stem cells, e.g. endothelial progenitors, mesenchymal, hematopoietic, cardiac stem cells and myoblasts, possess limited potential for multilinear differentiation. On the other hand these cells have high paracrin activity and support with well-confirmed safety the reconstruction and formation of cardiovascular structures. On the visionary track towards an autonomously functioning autologous heart generated by tissue engineering, vascular, valvular and myocardial tissues have already been successfully created. This manuscript describes the possible stem cell sources for cardiovascular tissue engineering and evaluates their potency and safety from a medical and ethical point of view employing the data from systematic reviews (Medline database) and own investigations.

Cardiac stem cell therapy. Registered trials and a pilot study in patients with dilated cardiomyopathy.

In cardiac stem cell therapy, the past decade has been interesting with respect to preclinical and clinical research. The high diversity of applied stem cell populations and evaluation methods represent a challenge to fully understand the impact of stem cell administration, leaving uncertain answers to the questions that have been dealt with thus far. In the present work, registered studies in cardiac stem cell therapy are summarized and the study aims are highlighted. Furthermore, preliminary data on the additional intramyocardial administration of CD133+ stem cells in patients undergoing mitral valve surgery are presented.

Traumatic arteriovenous fistula of the internal mammary vessels.

An uncommon case of traumatic arteriovenous fistula of the left internal mammary artery following penetrating chest trauma is presented. The patient developed a left parasternal machinery murmur six days after thoracotomy to repair a pericardial tamponade after a penetrating left parasternal stab wound. Selective digital subtraction angiography revealed pseudoaneurysm formation with fistulous connection of the left internal mammary artery to the adjacent vein. The fistula was successfully occluded with coil embolization.

Gallium nitride electrodes for membrane-based electrochemical biosensors.

We report on the deposition of planar lipid bilayers (supported membranes) on gallium nitride (GaN) electrodes for potential applications as membrane-based biosensors. The kinetics of the lipid membrane formation upon vesicle fusion were monitored by simultaneous measurements of resistance and capacitance of the membrane using AC impedance spectroscopy in the frequency range between 50 mHz and 50 kHz. We could identify a two-step process of membrane spreading and self-healing. Despite its relatively low resistance, the membrane can be modeled by a parallel combination of an ideal resistor and capacitor, indicating that the membrane efficiently blocks the diffusion of ions.

Cell sources for cardiovascular tissue regeneration and engineering.

The heart has long been regarded as a post-mitotic organ. Since many years, physicians have focused on developing strategies to restore the myocardium after ischemic damage followed by ventricular dysfunction. Restoration is generally achieved through the redirection of blood flow or by supporting contractile performance. The discovery of stem cells capable of generating angiogenic or contractile cells and structures offers new horizons to patients suffering from myocardial disease. Experimental studies indicate that the delivery or mobilization of stem and progenitor cells may improve tissue perfusion and the contractile performance of the damaged heart. Another aspect of restoration is based on cardiovascular tissue engineering and the creation of three-dimensional biological conformations to replace the artificial materials frequently used during operations, i.e., valves and grafts, or even a portion of the nonfunctional myocardial tissue. At present, the underlying intra- and intercellular molecular mechanisms controlling myocardiogenesis and cardiomyocyte replacement during regenerative processes are not very well understood. In this brief review we try to give the answers to questions on certain aspects of myocardial tissue regeneration and engineering procedures.

[From basic research to the clinic. Regulations for preclinical and clinical studies with stem cells]. / Von der Grundlagenforschung in die Klinik. Regulative Anforderungen an präklinische und klinische Studien mit Stammzellen.

The discovery of human embryonic stem cells at the end of 1998 had a strong influence on the development of stem cell research and led to controversial discussions. The first therapeutic application of adult blood stem cells began after their discovery in 1963 and was accepted as an authorized therapy in the early 1980s. The way from basic research to therapeutic use needed about 20 years and was also discussed in a controversial way similar to the discussions of today. The regulatory environment at that time, however, allowed a quick translation of the results from basic research to the clinic. Today many new stem cell therapies for a multitude of diseases are under development. Their clinical realization is regulated by the AMG (Arzneimittelgesetz). For nonclinical research as well as for clinical research, specific regulations are enacted to guarantee a structured and safe launch. Time, know how and money for planning, request for authorization and conduction of a clinical trial should not be underestimated. For clinical application of stem cell products authorization by the proper authorities is mandatory.

Intracardiac erythropoietin injection reveals antiinflammatory potential and improved cardiac functions detected by Forced Swim Test.

Systemic administration of erythropoietin (Epo) protects the myocardium from an ischemic insult and promotes beneficial remodeling. We hypothesized that intracardiac injection of Epo may exhibit cardioprotective potential with reduced systemic toxicity. Following myocardial infarction (MI), Epo was injected directly into the border of the infarction. Six weeks after an MI, we evaluated infarction size, angiogenesis, and pathologic effects of the treatment. Myocardial performance was assessed with a Forced Swim Test adapted to the study. Anti-inflammatory and cellular proliferative effects of Epo were analyzed by measuring expression of integrin-beta and CdK4 by reverse transcriptase-polymerase chain reaction (RT-PCR). The findings indicated improved cardiac status with direct Epo administration. Exercise capacity detected by the Forced Swim Test was significantly increased. There was radical reduction of absolute infarction size, ventricular dilatation, and hypertrophy in the Epo group. Integrin-beta was down-regulated and CdK4 expression was increased significantly with Epo. In conclusion, the study demonstrated that intramyocardial Epo injection, following MI, reduced inflammation, enhanced angiogenesis and proliferation, improved myocardial functions, and did not lead to intramural thrombus formation.

Direct minimally invasive intramyocardial injection of bone marrow-derived AC133+ stem cells in patients with refractory ischemia: preliminary results.

BACKGROUND: Bone marrow-derived stem cells (BMSC) may represent a viable option for patients with myocardial ischemia refractory to conventional treatments. MATERIAL AND METHODS: In 5 patients (4 males and 1 female, mean age 64 +/- 8 years) with untreatable angina pectoris (Canadian Cardiovascular Society Class III/IV), myocardial segments with stress-induced ischemia as assessed by gated single-photon emission computed tomography were injected with 4 to 12 million CD133+ BMSC. Cells were injected into the myocardium (2 anterior, 2 lateral, 1 inferior wall) through minimally invasive approaches (left minithoracotomy [n = 4] and subdiaphragmatic approach [n = 1]). At baseline, at 6 months and at 1 year of follow-up, an exercise test, gated single-photon emission computed tomography (SPECT), 2-D echocardiography and coronary angiography were performed to assess exercise capacity, myocardial perfusion, LV function and coronary anatomy. RESULTS: Intramyocardial injection of autologous CD133+ BMSC cells was safe. No early or long-term complications were observed. After an average of 3.8 weeks from cell inoculation, all patients experienced a significant improvement of CCS class (from 3.8 to 1.8 at 6 months) and serial SPECT documented improvements of rest and stress perfusion in the injected territories at 6 months from operation. In 3 cases, coronary angiography showed an increase in the collateral score of the target areas. Clinical improvements still persist unchanged in 4 out of 5 cases at a mean of 36.5 months postoperatively. CONCLUSIONS: After stand-alone BMSC transplantation for refractory myocardial ischemia, we observed long-term clinical and perfusion improvements in the absence of adverse events.

Novel material concepts of transducers for chemical and biosensors.

The objectives of this work are to contribute to the knowledge about physical and chemical properties of WBG semiconductors, such as ZnO and GaN towards development of advanced bio- and chemical sensors. For the semiconductors, growth techniques typically yielding single crystal material are applied. Thin epitaxial quality films of ZnO and GaN are fabricated on SiC or sapphire substrates. An emphasis is given to ZnO due to the interesting combination of the semiconductor and oxide properties. Surface bio-functionalization of ZnO is performed by APTES, MPA or MP-TMS molecules. We have compared some of the results to (hydroxylated) GaN surfaces functionalized by MP-TMS. The covalent attachment of the self-assembled biomolecular layers has been proven by XPS analysis. For complementary electrical characterization impedance spectroscopy measurements were performed. The results are intended to serve the realization of bioelectronic transducer devices based on SiC or GaN transistors with a ZnO gate layer. To take advantage of the catalytic properties of ZnO, initial prototypes of chemical sensors for gas sensing are processed on ZnO deposited either on SiC or on sapphire and they are further tested for the response to reducing or oxidizing gas ambient. The sensor devices show sensitivity to oxygen in the surface resistivity mode while a Pt Schottky contact ZnO/SiC device responds to reducing gases. These results are compared to published results on Pt/GaN Schottky diodes.

Endothelial nitric oxide synthase mediates protective effects of hypoxic preconditioning in lungs.

To elucidate the protective mechanism of whole-body hypoxic preconditioning (WHPC) on pulmonary ischemia-reperfusion injury focussing on nitric oxide synthases (NOS), mice were placed in a hypoxic chamber (FIO(2)=0.1) for 4h followed by 12h of normoxia. Then, pulmonary ischemia for 1h followed by 5h of reperfusion was performed by clamping the left hilum in vivo (I/R). WHPC protected WT mice from pulmonary leukocyte infiltration as assessed by myeloperoxidase (MPO) activity, associated with a mild further increase in endothelial permeability (Evans Blue extravasation). When all NOS isoforms were inhibited during WHPC by L-NAME, mortality and MPO activity after I/R markedly increased. To determine the responsible NOS isoform, quantitative RT-PCR was performed for eNOS and iNOS mRNA, showing that only eNOS was upregulated in response to WHPC. While eNOS total protein expression remained unchanged, the amount of phosphorylated eNOS also increased. The WHPC/IR experiments were then repeated with eNOS knockout mice. Here, we found that the protective effect of WHPC on pulmonary leukocyte sequestration was abrogated, and endothelial leakage was further exacerbated. We conclude that WHPC limits neutrophil sequestration via an eNOS-dependent mechanism, and that eNOS helps preserve endothelial permeability during hypoxia and I/R.

The effects of the dual 5alpha-reductase inhibitor dutasteride on localized prostate cancer--results from a 4-month pre-radical prostatectomy study.

BACKGROUND: As dihydrotestosterone (DHT) is the most potent androgen in the prostate, inhibition of the 5alpha-reductase isoenzymes, which convert testosterone to DHT, could be an appropriate target for the treatment of prostate cancer. METHODS: Eighty-one men with clinically localized prostate cancer received daily dutasteride 3.5 or 0.5 mg, or no therapy for 4 months before radical prostatectomy. Histopathological assessments were conducted on prostatectomy specimens. RESULTS: Treatment with dutasteride was associated with reductions in serum and intraprostatic DHT of >or=90%, and a decrease in total prostate and tumor volumes. No effect of dutasteride was noted on Gleason grade. Histopathological effects on benign tissue were similar but less prominent than those seen with androgen ablation, whereas there was no significant difference in cancer histology among the groups. CONCLUSIONS: Dutasteride treatment results in similar but less marked changes compared with androgen ablation.