Analysis of dispersive interactions at polymer/TiAlN interfaces by means of dynamic force spectroscopy.

The structural and electronic origins of the interactions between polycarbonate and sputter deposited TiAlN were analysed using a combined electron and force spectroscopic approach. Interaction forces were measured by means of dynamic force spectroscopy and the surface polarizability was analysed by X-ray photoelectron valence band spectroscopy. It could be shown that the adhesive interactions between polycarbonate and TiAlN are governed by van der Waals forces. Different surface cleansing and oxidizing treatments were investigated and the effect of the surface chemistry on the force interactions was analysed. Intense surface oxidation resulted in a decreased adhesion force by a factor of two due to the formation of a 2 nm thick Ti0.21Al0.45O surface oxide layer. The origin of the residual adhesion forces caused by the mixed Ti0.21Al0.45O surface oxide was clarified by considering the non-retarded Hamaker coefficients as calculated by Lifshitz theory, based on optical data from Reflection Electron Energy Loss Spectroscopy. This disclosed increased dispersion forces of Ti0.21Al0.45O due to the presence of Ti(iv) ions and related Ti 3d band optical transitions.

Fibroblast growth factor 2 is of prognostic value for patients with locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: Patients with locally advanced SCCHN have a poor prognosis. This study investigated the prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients treated with surgery followed by radiotherapy. PATIENTS AND METHODS: The impact of FGF-2-expression and 11 additional potential prognostic factors on loco-regional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively evaluated in 146 patients. Additional factors included age, gender, performance status, pre-radiotherapy hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papilloma virus (HPV) status, extent of resection, and chemotherapy. Univariate analyses were performed with the Kaplan-Meier method and the log-rank test, multivariate analyses with the Cox proportional hazard model. RESULTS: On multivariate analysis, improved LRC was significantly associated with FGF-2-negativity [risk ratio (RR): 7.33; 95%-confidence interval (CI): 2.88-19.05; p<0.001], lower T-category (RR: 2.42; 95%-CI: 1.47-4.33; p<0.001), lower N-category (RR: 12.36; 95%-CI: 3.48-78.91; p<0.001), and pre-radiotherapy hemoglobin levels ≥ 12 g/dl (RR: 4.18; 95%-CI: 1.73-10.53; p=0.002). No factor was significantly associated with improved MFS. Lower T-category showed a trend (RR: 1.59; 95%-CI: 0.97-2.82; p=0.069). Better OS was significantly associated with FGF-2-negativity (RR: 5.10; 2.22-11.80; p<0.001), lower T-category (RR: 2.17; 95%-CI: 1.38-3.68; p < 0.001), lower N-category (RR: 3.86; 95%-CI: 1.60-10.85; p=0.002), and pre-radiotherapy hemoglobin levels ≥ 12 g/dl (RR: 3.20; 95%-CI: 1.46-7.30; p=0.004). HPV-positivity showed a trend (RR: 2.36; 95%-CI: n.a.; p=0.054). CONCLUSIONS: Tumor cell expression of FGF-2 proved to be an independent prognostic factor for LRC and OS. This factor can help personalize treatment and stratify patients in future trials.

Laryngomalacia and complicated, life-threatening mTOR-positive Kaposiform hemangioendothelioma cured by Supraglottoplasty and sirolimus.

The therapy of complicated Kaposiform hemangioendothelioma (KHE) is still difficult. We present the first case of laryngomalacia with simultaneous mammalian target of Rapamycin (mTOR)-positive KHE of the neck and thoracic inlet and concurrent Kasabach-Meritt Phenomenon (KMP) in an 11-month-old boy suffering life-threatening progress despite intravenous vincristine, corticosteroids, propranolol and local interstitial laser-application. The laryngomalacia restored after laser-supraglottoplasty. Successfully treatment of the prior fatal course of the KHE with KMP was initiated not till adding the mTOR inhibitor sirolimus to therapy. After 16 months single therapy of KHE with oral sirolimus the boy presented free of symptoms with minimal residual disease and excellent functional long-term results. Thus we stopped sirolimus therapy. The results are stable for 9 months without therapy. The special features including full report of histopathologic findings of this utmost complicated case are demonstrated in detail underlining the effectiveness of sirolimus for KHE.

Prognosis of patients with locally advanced squamous cell carcinoma of the head and neck. Impact of tumor cell expression of EPO and EPO-R.

BACKGROUND AND PURPOSE: This study investigated the prognostic role of tumor cell expression of erythropoietin (EPO) and its receptor (EPO-R) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) treated with surgery plus radiotherapy. PATIENTS AND METHODS: The impact of EPO, EPO-R, and 11 additional factors on locoregional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively evaluated in 144 patients. Additional factors were age, gender, performance status, preradiotherapy (pre-RT) hemoglobin levels, tumor site, histologic grade, T category, N category, human papillomavirus (HPV) status, extent of resection, and chemotherapy. Univariate analyses were performed with the Kaplan-Meier method and the log-rank test, multivariate analyses with the Cox proportional hazard model. RESULTS: On multivariate analysis, improved LRC was significantly associated with no EPO expression (risk ratio [RR] 3.72; 95 % confidence interval [CI] 1.35-15.42; p = 0.008), lower T category (RR 1.60; 95 %CI 1.14-2.32; p = 0.005), and oropharynx or larynx cancer (RR 1.23; 95 %CI 1.02-1.49; p = 0.033). Improved MFS was significantly associated with no EPO expression (RR 5.45; 95 %CI 1.13-97.81; p = 0.031), lower T category (RR 1.66; 95 %CI 1.11-2.65; p = 0.013), lower N category (RR 2.44; 95 %CI 1.04-6.66; p = 0.039), HPV positivity (RR 3.14; 95 %CI not available; p = 0.034), and oropharynx or larynx cancer (RR 1.28; 95 %CI 1.01-1.61; p = 0.041). Improved OS was significantly associated with no EPO expression (RR 4.77; 95 %CI 1.63-20.68; p = 0.003), no EPO-R expression (RR 2.36; 95 %CI 1.22-4.92; p = 0.010), lower T category (RR 1.44; 95 %CI 1.04-2.04; p = 0.027), oropharynx or larynx cancer (RR 1.30; 95 %CI 1.08-1.57; p = 0.007), and pre-RT hemoglobin ≥ 12 g/dl (RR 1.94; 95 %CI 1.03-3.65; p = 0.042). CONCLUSION: EPO expression of tumor cells was an independent prognostic factor for LRC, MFS, and OS. EPO-R expression was an independent prognostic factor for OS.

Prognostic impact of VEGF and FLT-1 receptor expression in patients with locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: This study investigated the prognostic value of tumor cell expression of vascular endothelial growth factor (VEGF) and its receptor fms-related tyrosine kinase 1 (FLT-1) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) who had been treated with adjuvant radiotherapy or radiochemotherapy. MATERIAL AND METHODS: The impact of tumor cell VEGF and FLT-1 expression plus 11 additional factors on loco-regional control (LRC), metastases-free survival (MFS) and overall survival (OS) was retrospectively evaluated in 157 patients. The additional factors were age, gender, performance status, pre-radiotherapy (pre-RT) hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papillomavirus (HPV) status, extent of resection and chemotherapy. RESULTS: On multivariate analysis, improved LRC was significantly associated with an absence of VEGF expression (risk ratio, RR: 5.02; p = 0.009), lower T-category (RR: 2.00; p < 0.001), lower N-category (RR: 3.75; p < 0.001) and pre-RT hemoglobin levels ≥ 12 g/dl (RR: 2.20; p = 0.029). Improved MFS was significantly associated with an absence of VEGF expression (RR: 7.46; p = 0.002), lower T-category (RR: 1.97; p = 0.002), lower N-category (RR: 3.29; p = 0.005) and a favorable tumor location (RR: 1.34; p = 0.033); HPV positivity showed a trend towards improved MFS (RR: 1.43; p = 0.09). Improved OS was significantly associated with an absence of VEFG expression (RR: 3.22; p = 0.041), pre-RT hemoglobin levels ≥ 12 g/dl (RR: 2.47; p = 0.009), lower T-category (RR: 1.92; p < 0.001) and lower N-category (RR: 3.39; p < 0.001). FLT-1 expression was significantly associated with LRC and OS in the univariate but not in the multivariate analysis. CONCLUSION: VEGF expression proved to be an independent negative predictor for LRC, MFS and OS in patients treated for locally advanced SCCHN with adjuvant radiotherapy or radiochemotherapy. FLT-1 expression was not significant in multivariate analyses.

Androgen receptor expression: prognostic value in locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: This study investigated the prognostic value of androgen receptor (AR) expression of tumor cells in patients treated with surgery and subsequent radio(chemo)therapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN). MATERIAL AND METHODS: The impact of AR and 11 additional factors on locoregional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively studied in 163 patients with nonmetastatic stage III/IV SCCHN. Additional factors included age, gender, ECOG performance status, pre-radiotherapy (pre-RT) hemoglobin levels, tumor site, histologic grade, T category, N category, HPV status, extent of resection, and concurrent chemotherapy. RESULTS: On multivariate analysis, improved LRC was significantly associated with pre-RT hemoglobin levels≥12 g/dl (risk ratio [RR] 2.22; 95% confidence interval [CI] 1.19­4.13; p=0.013), tumor site (RR 1.39; 95% CI 1.14­1.70; p=0.001), lower T category (RR 1.67; 95% CI 1.18­2.44; p=0.003), and lower N category (RR 4.18; 95% CI 1.90­10.55; p<0.001). Improved MFS was associated with AR expression (RR 2.21; 95% CI 1.01­5.41; p=0.048), better ECOG performance status (RR 3.19; 95% CI 1.50­7.14; p=0.003), lower T category (RR 2.24; 95% CI 1.47­3.65; p<0.001), and lower N category (RR 5.33; 95% CI 2.07­16.63; p<0.001). OS was positively associated with AR expression (RR 1.99; 95% CI 1.06­4.00; p=0.032), better ECOG performance status (RR 2.20; 95% CI 1.20­4.09; p=0.010), pre-RT hemoglobin levels≥12 g/dl (RR 2.13; 95% CI 1.19­3.82; p=0.012), lower T category (RR 1.81; 95% CI 1.30­2.62; p<0.001), and lower N category (RR 3.41; 95% CI: 1.65­7.80; p<0.001). CONCLUSION: Tumor cell expression of AR was an independent prognostic factor for MFS and OS and should be considered in future prospective trials.

Impact of the HPV-positivity definition on the prognostic value of HPV status in patients with locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: This study re-evaluated the prognostic value of HPV status for loco-regional control (LRC), metastases-free survival (MFS), and survival (OS) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). A modified definition of HPV positivity was used in the current study compared to the authors' previous study. PATIENTS AND METHODS: In the previous study of the same 170 patients, a tumor was defined as HPV-positive if it showed a positive in situ hybridization result in ≥10% of tumor cells and/or positive p16 immunostaining. In the current analysis, tumors were considered HPV-positive only if they showed positive results for both in situ hybridization and p16 immunostaining. In addition to HPV status, the same 11 potential prognostic factors were investigated for treatment outcomes as in the preceding study. RESULTS: In the multivariate analysis of the current study, HPV positivity was significantly associated with improved LRC [risk ratio (RR) 9.78; p<0.001], MFS (RR 7.17; p=0.008), and OS (RR 6.61; p<0.001). In the previous study, HPV positivity was associated with LRC (RR 2.34; p=0.014) and OS (RR 2.19; p=0.019), but not with MFS (RR 2.04; p=0.11). CONCLUSIONS: Applying the new definition of HPV positivity, the impact of HPV status on the prognosis of patients irradiated for locally advanced SCCHN was more prominent than in our previous study and associated with all three investigated endpoints.

[Dysplasia and laryngeal carcinoma in situ]. / Dysplasien und Carcinomata in situ des Larynx.

Although the glottis is amenable to chemotherapy, currently most lesions from stage I laryngeal dysplasia up to carcinoma in situ are excised. This literature review presents selected molecular biological aspects especially in relation to dysplasia of the larynx and its therapy, as well as currently preferred biomarkers for chemotherapeutic prevention of laryngeal dysplasia.

Four-dimensional imaging and quantitative reconstruction to analyse complex spatiotemporal processes in live cells.

Live-cell imaging technology using fluorescent proteins (green fluorescent protein and its homologues) has revolutionized the study of cellular dynamics. But tools that can quantitatively analyse complex spatiotemporal processes in live cells remain lacking. Here we describe a new technique--fast multi-colour four-dimensional imaging combined with automated and quantitative time-space reconstruction--to fill this gap. As a proof of principle, we apply this method to study the re-formation of the nuclear envelope in live cells. Four-dimensional imaging of three spectrally distinct fluorescent proteins is used to simultaneously visualize three different cellular compartments at high speed and with high spatial resolution. The highly complex data, comprising several thousand images from a single cell, were quantitatively reconstructed in time-space by software developed in-house. This analysis reveals quantitative and qualitative insights into the highly ordered topology of nuclear envelope formation, in correlation with chromatin expansion - results that would have been impossible to achieve by manual inspection alone. Our new technique will greatly facilitate study of the highly ordered dynamic architecture of eukaryotic cells.

[A comparison of the use of electrochemical treatment and radio frequency ablation in porcine liver]. / Intrahepatische Ablation: Radiofrequenzablation versus Elektrochemische Lyse.

BACKGROUND: Radiofrequency ablation (RFA) and electrochemical treatment (ECT) are competing methods of intrahepatic ablation. We compared RFA and ECT in a perfusion model and in vivo in pigs. MATERIAL AND METHODS: Twenty-seven fresh porcine livers were obtained from a slaughterhouse and placed ex vivo into a perfusion model. RFA or ECT electrodes were inserted under ultrasound guidance in perivascular locations at a distance of 10 mm from a portal vessel. A total of 83 areas of ablation were created. In vivo ablations were performed at perivascular sites in 10 laparotomised pigs. Four areas of ablation were created per liver using RFA or ECL. Inflammatory parameters, liver values and cytokine levels were determined before and after surgery and on days 1, 3 and 7 after surgery. On day 7, the livers were harvested and specimens were analysed histo-logically by independent experts. RESULTS: In 29% of 59 ex vivo RFA ablations, the target temperature was not reached and the procedure was discontinued. Intact hepatocytes were detected in close proximity to 70 % of the vessels within necrotic areas. In 24 ECT applications, treatment time depended on the charge delivered and ranged between 50 min at 150 coulombs (C) and 200 min at 600 C. The pH level was 0.9 at the anode and 12.2 at the cathode. ECT always led to complete perivascular necrosis and vessel wall destruction. The animals had an in vivo -median weight of 39.5 kg. Neither RFA nor ECT caused major complications such as bleeding, bile leaks or abscesses. Treatment time was 67 min (200 C) for ECT and 12.4 min for RFA. In 73% of the cases, RFA led to incomplete perivascular areas of necrosis. ECT induced complete perivascular necrosis and vessel wall destruction. On day 1 after surgery, both ECT and RFA were associated with a significant increase in monocyte, C-reactive protein and aspartate aminotransferase levels. Leukocyte counts were elevated only after ECT, bilirubin levels only after RFA. There were no significant differences in interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and IL-1ß. CONCLUSION: Both RFA and ECL are safe methods of intrahepatic ablation. As a result of a heat sink effect of blood flow in nearby vessels, RFA leads to incomplete necrosis in perivascular sites both ex vivo and in vivo. ECT has the disadvantage of long treatment times but the advantage of lower costs since the platinum electrodes are reusable. Without a reduction in liver perfusion, the central application of RFA in close proximity to vessels should be considered problematic.

Chronic alcohol intake increases the severity of pancreatitis induced by acute alcohol administration, hyperlipidemia and pancreatic duct obstruction in rats.

BACKGROUND: The mechanism of alcoholic pancreatitis is still unknown. It is of special interest why only about 5% of all alcoholics develop an episode of pancreatitis. We evaluated the role of long-term alcohol intake in the pathogenesis of alcoholic pancreatitis in rats. METHODS: To evaluate the effect of long-term alcohol intake, rats were fed either a Lieber-DeCarli control diet (CD) or a Lieber-DeCarli alcohol diet (AD) for 6 weeks. Then, rats were infused over 2 h with either Ringer's solution (CO) or ethanol (E). In additional animals, alcoholic pancreatitis was induced by ethanol combined with hyperlipidemia and temporary pancreatic duct obstruction (EFO). Controls received Ringer's solution combined with hyperlipidemia and temporary pancreatic duct obstruction (RFO). Intravital microscopy (pancreatic perfusion and leukocyte adhesion), alcohol concentrations, amylase, lipase, cholesterine and triglyceride levels in plasma, myeloperoxidase activity and histology were evaluated at different time intervals. RESULTS: In those animals which received the Lieber-DeCarli control diet, capillary perfusion was reduced in the E group and further reduced in the EFO group as compared to the controls (CO, RFO; p < 0.01). Leukocyte adhesion was significantly increased in rats receiving E (p < 0.01), and was further increased in the combination group EFO (p < 0.01). EFO induced histologically evident acute pancreatitis. The additional administration of a long-term alcohol diet further increased microcirculatory disturbances and pancreatic injury significantly (EFO-AD > EFO-CD). CONCLUSIONS: This study shows that alcoholic pancreatitis is induced by the combination of ethanol and individual cofactors. Chronic alcohol abuse intensifies these changes. Therefore, long-term alcohol intake seems to be a major factor in the pathogenesis of alcoholic pancreatitis.

[Analysis of 18F-FDG uptake pattern in PET for diagnosis of aseptic loosening versus prosthesis infection after total knee arthroplasty. A prospective pilot study]. / Analyse des 18F-FDG-Speichermusters in der PET zur Differenzierung zwischen aseptischer Prothesenlockerung und Protheseninfektion - Eine prospektive Pilotstudie.

UNLABELLED: The AIM of this prospective study was to identify a typical pattern for fluorodeoxyglucose (18F-FDG) uptake in positron emission tomography (PET) to differentiate aseptic loosening (tibial and / or femoral component) from prosthesis infection in painful knee prosthesis. PATIENTS, METHODS: 20 patients with painful knee prosthesis underwent PET imaging to evaluate aseptic loosening / prosthesis infection of their knee prosthesis. The interface between bone and surrounding soft tissue or bone was divided into 3 segments each for both the femur and the tibia and in addition for 4 segments reflecting the surrounding periprosthetic soft tissue. FDG uptake in each of the segments was scored (0-3) by two independent observers. The final diagnosis was based on operative findings with subsequent microbiological culture and histological examination. RESULTS: After surgical revision 6 femoral components and 5 tibial components were found to be loose and prosthetic infection was present in 9 prostheses. In 8 of 9 infected prostheses loosening of the femoral und tibial component occurred. There was no statistically significant correlation between the standardised uptake within each of the segments and the diagnosis of aseptic loosening or prosthesis infection. A differentiated qualitative and quantitative FDG-PET result interpretation divided into five categories was developed. Specificity / sensitivity / positive predictive value / negative predictive value were 93% / 83% / 83% / 93% for aseptic loosening of the femoral component, 87% / 80% / 67% / 93% for aseptic loosening of the tibial component and 82% / 89% / 80% / 90% for infection. CONCLUSION: This pilot study shows that FDG-PET is a promising diagnostic tool for patients with painful knee prostheses. There is a good correlation between PET images and the intraoperative and pathology findings. Its clinical value, however, warrants further evaluation in a larger patient population.

Hibernoma-case report and literature review.

Hibernoma is an uncommon benign fatty tumor that arises from the vestiges of fetal brown fat. We present a case report of a hibernoma of the back in a symptomatic 42-year-old man and describe the important clinical, histopathologic, and imaging findings. Computed tomography shows a well-defined hypodense mass with septations. Magnetic resonance imaging shows intermediate T1 and bright T2 signal of the mass and also demonstrates the characteristic marked contrast enhancement.

Bradykinin in ischemia-reperfusion injury of the rat lung.

Recent studies described possibilities to reduce lung damage after intestinal ischemia by application of a selective bradykinin-2 receptor antagonist (HOE 140). In contrast, it has been shown that the preischemic application of bradykinin (BK) reduced ischemic damage of the myocardium. In the present study, to evaluate the effects of BK and HOE 140 in lung ischemia-reperfusion injury we used a standardized in vivo ischemia-reperfusion model of the right rat lung. Ischemia of 60 min was induced by cross-clamping of the right hilus followed by 120 min of reperfusion. During reperfusion, the left hilus was ligated. In Group 1 (n=5), the animals were sham operated without induction of ischemia under ligation of the left lung hilus. Group 2 (n=5) was operated as described, Group 3 (n=5) received 100 microg bradykinin (BK) before reperfusion, Group 4 (n=5) was given a B2-agonist before reperfusion, and Group 5 (n=5) was given 100 microg HOE140/kg body weight before reperfusion. Blood pressure and arterial oxygenation were monitored. As a marker of endothelial damage, angiotensin-converting-enzyme activity (ACE) in serum and RT-PCR of ACE and angiotensin-2 in lung tissue were determined in all groups. Two of the HOE140-treated animals died within 30 min of reperfusion. During reperfusion, significantly higher PaO2 values (P<0.01) have been observed in BK treated animals of Group 3 (214+/-22 mmHg) and sham operated controls of Group 1 (233+/-26 mmHg) compared with Groups 2 (132+/-13 mmHg) and Group 5 (125+/-50 mmHg; P<0.01). Serum ACE activity after reperfusion was significantly lower in Group 1 (3.5+/-0.5 IU/l), Group 3 (3.8+/-1.1 IU/l), and Group 4 (2.2+/-0.5 IU/l; P<0.05) vs. Group 2 (4.8+/-0.9 IU/l), whereas Group 5 (6.2+/-5.4 IU/l) did not differ from Group 2. mRNA expressions of ACE was lower in Group 1 and Group 3 compared with Group 2 (P<0.01). AT-2 mRNA expression did not show any differences between the investigated groups. A significantly lower ACE activity and expression and a significantly higher oxygenation after BK application in Group 3 strongly suggest a positive influence of bradykinin on ischemic preconditioning of the pulmonary endothelium. Positive effects of application of bradykinin-receptor antagonists could not be proved in this study.

Alterations of tumor and normal tissue of human lung cancer resection specimens after isolation perfusion.

The isolation perfusion model, including transbronchial ventilation of human lung, offers the possibility to study pharmacological interactions under physiological conditions. In view of the increasing importance of targeted therapy of lung diseases, this model of perfusion might attract major interest, particularly, in lung cancer. Our study investigated physiological, histological, and immunohistochemical alterations of lung and tumor tissue during isolated perfusion of lung lobectomy specimens to explore potential limitations of this model. Right after resection, 16 human lung resection specimens for primary lung cancer were isolated, ventilated, and perfused under physiological conditions with a modified Krebs-Henseleit solution over a period of 10, 60, 90, 120, and 240 min. Perfusion pressure, pH, lung weight gain, and histological edema formation were measured continuously before and during perfusion. After perfusion, lung and tumor tissue was investigated by hematoxylin-and-eosin stained sections. Immunohistochemistry of NADH, PECAM-1, angiotensin-converting-enzyme and NF-kappabeta were performed to determine lung tissue viability and changes at the endothelial layer. We found that perfusion up to 120 min could be performed with completely stable physiological conditions. Beyond that time span, edema formation and weight gain of the resection specimen started and were followed by an increase in inspiratory pressure and pulmonary artery pressure. Perfusion of more than 4 h led to a significant edema formation in lung tissue accompanied by loss of viability and significant histological alterations. We conclude that isolated ventilation and perfusion of human lung resections within the setup chosen is reliable for pharmacological studies up to a period of 120 min. Thereafter, edema formation and endothelial damage develop and limit the interpretation and reliability of drug delivery studies.

Taurine protects from liver injury after warm ischemia in rats: the role of kupffer cells.

BACKGROUND/AIMS: Warm ischemia to liver with subsequent Kupffer cell-dependent pathology is associated with many clinical conditions. Taurine prevents Kupffer cell activation and improves graft survival after experimental cold ischemia and liver transplantation. Thus this study was designed to assess its effects after warm hepatic ischemia. METHODS: The left liver lobe of female Sprague-Dawley rats (170-210 g) underwent 60 min of warm ischemia. Animals were given either intravenous taurine or Ringer's solution 10 min prior to warm ischemia. Transaminases, histology, in vivo microscopy, intercellular adhesion molecules-1 (ICAM-1) expression, TNF-alpha and tissue hydroperoxide were compared between groups using analysis of variance (ANOVA) or ANOVA on ranks as appropriate. RESULTS: Taurine significantly decreased transaminases and improved histologic outcome. Phagocytosis of latex beads, serum TNF-alpha levels and tissue hydroperoxide concentrations were also significantly reduced. Stickers in sinusoids and post-sinusoidal venules significantly decreased. In parallel, both leukocyte infiltration and ICAM-1 expression decreased (p < 0.05), while flow velocity of red blood cells as well as sinusoidal perfusion rate were improved (p < 0.05). CONCLUSION: This study demonstrates that taurine blunts Kupffer cell-dependent hepatic pathology after warm ischemia in vivo via mechanisms including leukocyte-endothelial interaction, microcirculation disturbances and protection against lipid peroxidation.

New amidinate complexes of indium(iii): promising CVD precursors for transparent and conductive In2O3 thin films.

For the first time, synthesis of two new amidinate-ligand comprising heteroleptic indium complexes, namely [InCl(amd)2] (1) and [InMe(amd)2] (2), via salt-metathesis and their detailed characterization is reported. For comparison, the earlier reported homoleptic tris-amidinate [In(amd)3] (3) was also synthesized and analyzed in detail especially with respect to the thermal properties and molecular crystal structure analysis which are reported here for the first time. From nuclear magnetic resonance spectroscopy (NMR) and single-crystal X-ray diffraction (XRD), all three compounds were found to be monomeric with C2 (compound 1 and 2) and C3 symmetry (compound 3). Both halide-free compounds 2 and 3 were evaluated regarding their thermal properties using temperature-dependent 1H-NMR, thermogravimetric analysis (TGA) and iso-TGA, revealing suitable volatility and thermal stability for their application as potential precursors for chemical vapor phase thin film deposition methods. Indeed, metalorganic chemical vapor deposition (MOCVD) experiments over a broad temperature range (400 °C-700 °C) revealed the suitability of these two compounds to fabricate In2O3 thin films in the presence of oxygen on Si, thermally grown SiO2 and fused silica substrates. The as-deposited thin films were characterized in terms of their crystallinity via X-ray diffraction (XRD), morphology by scanning electron microscopy (SEM) and composition through complementary techniques such as Rutherford-backscattering spectrometry (RBS) in combination with nuclear reaction analysis (NRA) and X-ray photoelectron spectroscopy (XPS). From UV/Vis spectroscopy, the deposited In2O3 thin films on fused silica substrates were found to be highly transparent (T > 95% at 560 nm, compound 3). In addition, Hall measurements revealed high charge carrier densities of 1.8 × 1020 cm-3 (2) and 6.5 × 1019 cm-3 (3) with a Hall-mobility of 48 cm2 V-1 s-1 (2) and 74 cm2 V-1 s-1 (3) for the respective thin films, rendering the obtained thin films applicable as a transparent conducting oxide that could be suitable for optoelectronic applications.

Development and evaluation of a training module for the clinical introduction of the da Vinci robotic system in visceral and vascular surgery.

BACKGROUND: With the increasing use of the surgical robotic system in the clinical arena, appropriate training programs and assessment systems need to be established for mastery of this new technology. The authors aimed to design and evaluate a clinic-like training program for the clinical introduction of the da Vinci robotic system in visceral and vascular surgery. METHODS: Four trainees with different surgical levels of experience participated in this study using the da Vinci telemanipulator. Each participant started with an initial evaluation stage composed of standardized visceral and vascular operations (cholecystectomy, gastrotomy, anastomosis of the small intestine, and anastomosis of the aorta) in a porcine model. Then the participants went on to the training stage with the rat model, performing standardized visceral and vascular operations (gastrotomy, anastomosis of the large and small intestines, and anastomosis of the aorta) four times in four rats. The final evaluation stage was again identical to the initial stage. The operative times, the number of complications, and the performance quality of the participants were compared between the two evaluation stages to assess the impact of the training stage on the results. RESULTS: The operative times in the final evaluation stage were considerably shorter than in the initial evaluation stage and, except for cholecystectomies, all the differences reached statistical significance. Also, significantly fewer complications and improved quality for each operation in the final evaluation stage were documented, as compared with their counterparts in the initial evaluation stage. These improvements were recorded at each level of experience. CONCLUSIONS: The presented experimental small and large animal model is a standardized and reproducible training method for robotic surgery that allows evaluation of the surgical performance while shortening and optimizing the learning-curve.

Intravital microscopy of pulmonary microcirculation after single lung transplantation in pigs.

BACKGROUND: Pulmonary reperfusion injury is a significant risk factor following lung transplantation (LTx). Unfortunately, in vivo observations and quantitative analyses of the pulmonary microcirculation following LTx are technically demanding. METHODS: Pigs, weighing 18 to 22 kg, served as the laboratory animals. The left lung was harvested and preserved using donor aortic vessel segments, the pulmonary artery, and the cuff of the lung veins were extended. After 4 hours of ischemia, the lungs were transplanted by direct connection of the conduits to the left atrial appendage and the left pulmonary artery of the recipient. The lungs were placed extrathoracically and ventilated. The recipient left lung was excluded. With this procedure, mechanical trauma to the lung and moving artefacts were avoided. Intravital microscopic observation became feasible. RESULTS: Following reperfusion, oxygenation of pulmonary venous blood was excellent. However, blood flow distribution was significantly reduced to the transplanted lung compared with the native right recipient lung. Pulmonary vascular resistance was significantly increased, dropping from 3500 to 1000 dynes x s x cm(-5) during reperfusion compared to a value of 500 for the native right lung. The pulmonary microcirculation showed a significant number of no-reflow areas with extremely reduced red blood cell velocities. Greater than 90% of microvessels (<30 microm) showed velocities below 0.1 mm/sec. In conclusion, microvascular injury seems to be a major pathogenic factor for the development reperfusion failure. Quantification of alterations within the microvasculature may shed light on various treatment modalities that reduce perfusion failure.