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Background Complex posttraumatic stress disorder is described as a chronic condition with several severe and concurrent symptoms. Symptoms influence and impair not only the affected individuals but also their social surroundings and their relatives. The literature describes relatives as a key factor in managing symptoms, both as a barrier and a facilitator. Aim This research aimed to explore and to reconstruct the views, perceptions, experiences, facilitations and barriers of relatives who support the symptom management of persons with CPTSD in everyday life. Methods A theoretical sampling was used to recruit for an interview 18- to 65-year-old relatives of patients with diagnosed CPTSD. The 17 semi-structured interviews were audio-recorded and transcribed verbatim. The transcriptions were uploaded into MAXQDA, and a Grounded Theory method based on that of Corbin and Strauss was used to analyse the data. Results We provide a process model with 5 interacting phases: the initial situation, state of permanence, being an anchor, recognizing limits, and potential outcomes. Each phase is further divided into subcategories. Discussion Participants experienced their condition as unpredictable. Although they mastered different strategies through own exploration and in cooperation, there is a clear need for more education, advice and support for relatives caring for those affected by CPTSD. Health care services should consider providing family support, educational services and increase the involvement of relatives in treatment. Over all, well-supported relatives can play a facilitative, key role in improving symptom management. Trial registration Ethical approval was obtained from the Swiss Cantonal Ethic Commission (Nr 201,500,096). This research was also registered at the World Health Organization Clinical Trials Search Portal through the German Clinical Trial Register, Trial DRKS00012268.

Objective Using the framework of IDC-11, complex post-traumatic stress disorder will be diagnosed using the core criteria of a post-traumatic stress disorder and the presence of at least one symptom from the following three domains: symptoms of emotional dysregulation, negative self-concept, and problems in interpersonal relationships. In the literature, these symptoms are discussed as a common reason for seeking treatment. The symptoms can influence and impair the quality of life. This article describes a mixed methods study with a sequential exploratory design. The aim is to describe specific patient characteristics, levels of symptom burden and perspectives of adult inpatients and to describe the experiences, views and needs of patients’ relatives. The study will also investigate facilitators of and barriers to symptom management. The research will be conducted in four phases. The first phase will assess patients’ symptom burdens. The second phase will use semi-structured interviews to explore attitudes to symptom management and perceptions of patients and their relatives. The third phase will statistically explore hypotheses generated after the qualitative interviews. The fourth phase will mix the quantitative and qualitative results and interpret critically. Results The present study will add new results to the growing literature on complex post-traumatic stress disorder. These results could serve as the basis for further research into the development of interventions to improve symptom management. Trial registration Ethical approval has been obtained from the Swiss cantonal ethic commission (Nr. 201500096). This research was also registered to the World Health Organization Clinical Trials Search Portal through the German Clinical Trial Register, Trial DRKS00012268 (21/04/2017)

Introduction and hypothesis Bladder pain syndrome/interstitial cystitis (BPS/IC) is identified based on subjective symptoms which lead to heterogeneous patient populations. Previous studies using gene expression arrays for BPS/IC with Hunner’s lesions [European Society for the Study of Interstitial Cystitis (ESSIC) type 3C], a subtype of the condition discernible by cystoscopy, have revealed characteristic immune responses and urothelial abnormalities. This current study aimed to further characterize this subtype using a gene expression panel. We hypothesized that B-cell activation with high levels of urinary antibody concentration would be found. Methods Cold-cup bladder biopsies, catheterized urine and blood were collected from 15 BPS/IC ESSIC type 3C patients, 11 non-inflammatory overactive bladder (OAB) patients and eight healthy controls. Gene expression in biopsies was quantified by real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry was performed on bladder tissue and urinary immunoglobulins G and A were quantified by enzyme-linked immunosorbent assay. Statistical analyses included the Kruskal-Wallis test for non-parametric data and post hoc tests identified differences between groups. Results High expression of T- and B-cell markers (CTLA4, CD20, CD79A, IGH@), low expression of urothelial markers (KRT20, UPK1B, UPK3A), focal lymphoid aggregates in the submucosa and high immunoglobulin concentration in urine were found exclusively in BPS/IC ESSIC type 3C patients. Results for OAB were in intermediate ranges between the other two groups and UPK1B even reached significantly lower expression when compared to healthy controls. Conclusions BPS/IC ESSIC type 3C is characterized by a local adaptive immune response with elevated urinary antibody concentrations. Quantification of urinary immunoglobulin levels could be used for a non-invasive diagnosis of BPS/IC ESSIC type 3C.

The North China Plain (NCP) belongs to the major maize (Zea mays L.) growing areas in China. Maize yields have increased steadily since the 1980s, but in recent years average yields have stabilized around 5000 kg ha -1 . The objective of this study was to quantify the production potential of summer and spring maize in the NCP. For this purpose the CERES-Maize model was calibrated and validated. The variability caused by climate was considered by using up to 30 yr of weather data from 14 meteorological stations across the NCP. Simulations were carried out for five different soil texture. Results were linked to a Geographic Information System (GIS). The results of the model calibration and validation showed a good fit between simulated and measured yield. Average simulated grain yield for summer maize was 4800 kg ha -1 and for spring maize was 5700 kg ha -1 . Yields of summer maize were limited by the duration of the growing period. In order to increase spring maize yields, two strategies were developed. The first approach was to sow spring maize at a time when water deficit was least likely to occur during the late vegetative, flowering, and grain-filling stages. A delay in sowing of 30 d shifted maize development closer to the rainy season and increased average yield by 13%. In a second test the use of a variety with a later flowering date as a result of a longer vegetative growth led to an average increase in yield of 15%.

This research examines the impact of online–offline channel integration (OI), defined as integrating access to and knowledge about the offline channel into an online channel. Although channel integration has been acknowledged as a promising strategy for retailers, its effects on customer reactions toward retailers and across different channels remain unclear. Drawing on technology adoption research and diffusion theory, the authors conceptualize a theoretical model where perceived service quality and perceived risk of the Internet store mediate the impact of OI while the Internet shopping experience of customers moderates the impact of OI. The authors then test for the indirect, conditional effects of OI on search intentions, purchase intentions and willingness to pay. Importantly, they differentiate between retailer-level and channel-level effects, thereby controlling for interdependencies between different channels. The results of three studies provide converging evidence and show that OI leads to a competitive advantage and channel synergies rather than channel cannibalization. These findings have direct implications for marketers and retailers interested in understanding whether and how integrating different channels affects customer outcomes.

Advanced robotic surgery was first introduced into urology in 2000. The first studies showed the feasibility and safety of the daVinci (Intuitive Surgical Inc., Sunnyvale, CA) telemanipulator assistance in radical prostatectomy, pelvi-ureteric junction obstruction, and radical cystectomy and neobladder formation. The miniature endowristed tools offer a potential advantage over standard laparoscopy in the accuracy of preparation and suturing. Other features are a three-dimensional vision system and unimpaired hand-eye coordination. Complex laparoscopic tasks are learned faster by using the robot, which may also explain the shorter training required for radical prostatectomy than for manual laparoscopy. This new and expensive technology has spread rapidly over the last 4 years. By 2004, approximately 10% of radical prostatectomies in the USA will be robot-assisted. Data on the functional and oncological outcomes are accruing but not yet conclusive. There will be a further spread of robotic surgery, routine telesurgery, smaller and more affordable systems, the introduction of virtual reality, all developments which have the potential to urological surgeons to improve.

Neurological soft signs and neuropsychological (NP) impairments are prevalent in schizophrenic patients. However, the relationship of these deficits is rarely studied, and it remains controversial in what way soft signs influence NP performance. The Neurological Evaluation Scale (NES) and a comprehensive neuropsychological test battery were used to assess soft signs and cognitive functions in 61 first-episode schizophrenic patients. The NP test battery included tests such as the California Verbal Learning Test, the Continuous Performance Test, the Span of Apprehension Test, the Stroop Color-Word Test, the Trail-Making Test and the Wisconsin Card Sorting Test. The NP tests were also administered to 87 healthy controls. The first-episode schizophrenic patients were split along the median of their NES total score (SS- vs. SS+). The level of NP performance and the differences in relative performance (shape of the NP profile) on NP functions between the two groups were assessed. The two groups (SS- vs. SS+) did not differ in any demographic or clinical variable. However, they differed in the level of their NP performance (profile mean) but did not show differential deficits in NP performance (profile shape). Neurologic soft signs influence NP performance and are correlated to a generalized NP deficit rather than to any specific NP functions.

The robotic technique, which was first introduced in laparoscopic heart surgery, has revolutionized laparoscopic surgery over the last 5 years. In May 2000, our department accomplished the first robot assisted laparoscopic radical prostatectomy. Since that time we have performed more than 118 such procedures and several other laparoscopic operations using the robotic technique. We here summarize our experience in robot assisted laparoscopic radical prostatectomy as it has been developed over the past 3 years. Between May 2000 and May 2003, 118 patients with clinically localized prostate cancer were operated using the telerobotic da Vinci Surgical System. Operations were performed with a senior surgeon at the console, assisted by an assistant and a nurse at the operating table. Bilateral pelvic lymph node dissection was undertaken as a first step in all patients. In the initial 60 cases, we investigated different laparoscopic approaches. We used transperitoneal as well as extraperitoneal approaches. For dissection of the prostate we used ascending, descending as well as combined techniques. The combined ascending and descending technique via the transperitoneal route was chosen in 30 patients, and via the extraperitoneal route in seven patients. A modification of the descending Montsouris technique was performed in 81 patients. The robot assisted laparoscopic radical prostatectomy with the da Vinci system has been well standardized. After performing more than 100 radical prostatectomies with this system, we conclude that in our hands the Mountsouris technique with only minor adoptions is the most appropriate technique for performing robot assisted radical prostatectomy.

Laparoscopic radical prostatectomy is a complex procedure and has been standardized only during the last years. The remote controlled da Vinci Surgical System has opened up a new era in minimally invasive surgery. We here present our initial experience with the translation of open retropubic radical prostatectomy to laparoscopic technique using da Vinci and a one year follow-up.After a period of technical development and training on cadavers, 40 consecutive patients eligible for radical prostatectomy were treated. After port placement, the urologist took control of the 3D 30 degrees laparoscope and the two instrument arms at the da Vinci remote console to perform bilateral pelvic lymph node dissection, radical prostatovesiculectomy and urethrovesical anastomosis.The procedure was completed laparoscopically in all but two patients. Mean procedure time was 8.3 hours and mean intra-operative blood loss 570 ml. Learning curves associated with the use of the da Vinci Surgical System show that there is a 22-minute decrease in time required to perform the radical prostatectomy and lymphadenectomy for each case (p0.0001). Patients recovered rapidly after surgery with early oncological and functional results that were similar to those obtained with our standard radical prostatectomy technique.Remote controlled robotic surgical systems are useful to translate open retropubic radical prostatectomy to laparoscopy. This new technology has the potential to equip the urologist with the microsurgical precision needed to preserve the delicate structural integrity of the pelvic floor in order to improve functional results without compromising the oncological outcome.

Characterization of the endothelium-derived hyperpolarizing factor (EDHF) response in the human interlobar artery. Background In addition to nitric oxide (NO) and prostacyclin (PGI 2 ), the vascular endothelium can influence local vascular tone by a mechanism involving the hyperpolarization of vascular smooth muscle cells. This response is attributed to the release of an endothelium-derived hyperpolarizing factor (EDHF). The present study was performed to determine the characteristics of the EDHF that mediates the NO/PGI 2 -independent hyperpolarization and relaxation of human renal interlobar arteries. Methods Acetylcholine-induced, EDHF-mediated hyperpolarization and relaxation were assessed using sharp microelectrodes impaled into interlobar smooth muscle cells and in organ chamber experiments, respectively. All experiments were performed in the combined presence of NO synthase (NOS) and cyclooxygenase inhibitors and the thromboxane analog U46619. Results Interlobar arteries demonstrated pronounced NO/PGI 2 -independent relaxations and hyperpolarizations that were sensitive to the blockade of calcium-activated K + -channels ( K Ca + channels) by the combination of charybdotoxin and apamin and to the inhibition of the Na-K-ATPase by ouabain. Exogenously applied KCl also exhibited relaxations and hyperpolarizations that were sensitive to ouabain but insensitive to the combined inclusion of charybdotoxin and apamin. Relaxations induced by KCl were also observed in endothelium-denuded interlobar arteries. Conclusion These results indicate that in the human renal interlobar artery, EDHF-mediated responses display the pharmacologic characteristics of K + ions released through endothelial K Ca + channels. Smooth muscle cell hyperpolarization and relaxation appear to be dependent on the activation of ouabain-sensitive subunits of the Na-K-ATPase.

The potential role of angiogenesis stimulators in the pathogenesis of different tumor entities has been confirmed in several studies. We measured the serum levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) in 51 patients with testicular germ cell tumors and in 39 healthy volunteers. Serum concentrations of bFGF, VEGF and PDGF-AB were determined by enzyme-linked immunosorbent assay. The median serum bFGF level for tumor patients was 3.46 pg/ml (range 0–61.6) compared to 0.7 pg/ml (0–11) in the control group (P

Laparoscopic techniques have become a standard approach for diagnostic and therapeutic procedures in many surgical disciplines. Recent progress in endoscopic surgery is based on the integration of computer-enhanced telemanipulation systems. Because robot-assisted radical prostatectomies take up to 10 hours, the present study was performed to evaluate the effects of prolonged intraperitoneal CO2 insufflation on hemodynamics and gas exchange in 15 patients with prostate cancer. When CO2 insufflation was initiated, peak inspiratory pressure increased and reached significant values after a 1.5-hour period of intraperitoneal CO2 insufflation. With the release of CO2, peak inspiratory pressure decreased close to baseline values. A significant increase in heart rate was observed after a 4-hour period of increased intraabdominal pressure. Mean arterial blood pressure and central venous pressure remained stable during CO2 insufflation. Minute ventilation was adjusted according to repeated blood gas analyses to maintain pH, base excess (BE), bicarbonate (HCO 3 − ), and PaCO2 within physiologic ranges. The present data show, that prolonged CO2 insufflation during totally endoscopic robot-assisted radical prostatectomy results in only minor changes in hemodynamics and acid-base status. Because of the limited experience with long-term pneumoperitoneum, we consider invasive haemodynamic monitoring and repeat blood gas analysis essential for such operations.

Objective: Angiogenesis is essential for tumor growth and progression. However, reported data on angiogenic parameters in patients with renal cell carcinoma are contradictory. The objective of this study was to use serum to compare the systemic angiogenic activity in patients with renal cell carcinoma and to determine if pathologic stage and grade correlated to this angiogenesis parameter. Methods: Serum of 28 patients with a newly diagnosed renal cell carcinoma, 28 healthy volunteers and 9 patients with bladder carcinoma were used for this study. All sera were tested in a 72-hour endothelial cell proliferation assay. In addition the serum concentrations of the angiogenesis stimulators basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were determined using standard ELISA assays. Results: The serum of renal cell carcinoma patients showed a median stimulation of human umbilical vein endothelial cells (HUVEC) of 89.79% (range 58.47–147.95%) and serum of healthy volunteers showed a median stimulation of 95.35% (range 74.64–141.77%) ( p >0.05). In contrast serum of patients with bladder carcinoma showed a median stimulation of 140.16% (range 64.82–200.16%) ( p =0.024). No correlations of the serum angiogenic activity and tumor stage or grade have been found in renal cell carcinoma patients. Furthermore, no correlations for serum bFGF and VEGF concentrations have been found. Conclusions: Serum angiogenic activity of patients with renal cell carcinoma did not differ significantly from healthy controls, while serum of patients with bladder carcinoma showed a significant increase in endothelial cell stimulation. Furthermore, bFGF and VEGF serum concentrations did not correlate to serum angiogenic activity in patients with renal cell carcinoma. Therefore, the determination of systemic angiogenic parameters, in case of renal cell carcinoma, might not lead to adequate data concerning prognosis or therapeutic effects.

BACKGROUND Prostate cancer has historically been associated with coagulation abnormalities. This study was undertaken to investigate the prevalence of abnormalities of coagulation factors in patients with prostate cancer before and after radical prostatectomy (RP). Because coagulation factors have been shown to be involved in tumor angiogenesis, the vascular density of the prostate tumors was assessed. METHODS Plasma of 40 consecutive patients with histologically proven prostate cancer was investigated pre-RP and post-RP. The antigen level for antithrombin, plasminogen activator inhibitor-1, and heparin cofactor-II, and the plasma activity of antithrombin and plasminogen were determined by using immunologic and chromogenic assays. The values of these assays were compared with a group of 28 male, age-matched patients without any evidence of cancer and 18 patients with orthopedic interventions preoperatively and postoperatively. The vascular density of the prostate tumors was assessed by staining paraffin sections with an antibody to CD34. RESULTS The median plasma antigen levels and/or activities of the investigated factors were below normal in the prostate cancer patients before RP. Furthermore, coagulation factors were significantly lower than in the age-matched control group and patients before and after orthopedic surgery. In prostate cancer patients, the median values of all investigated factors went up to normal levels within 2 weeks after RP, whereas postsurgical levels in orthopedic patients remained stable. No correlations to tumor parameters have been observed. CONCLUSION We assume that the reduction of these coagulation factors is a principle concept in prostate cancer that needs further investigation. Prostate 53: 160–167, 2002. © 2002 Wiley-Liss, Inc.

Laparoscopic adrenalectomy is considered the standard method for removal of benign adrenal tumors. Although laparoscopic surgery provides clear patient benefit, laparoscopic adrenalectomy using conventional instrumentation is complex. Our objective was to evaluate whether the da Vinci trade mark Surgical System, a comprehensive robotic endoscopic surgical device, could be used effectively to perform laparoscopic adrenalectomy.Through a transperitoneal approach, three right and one left adrenal tumors were removed in four patients using this method.There were no complications, and the clinical results were excellent.We demonstrate the feasibility of performing laparoscopic adrenalectomy exclusively by using robotic telepresent technology from a remote workstation. The da Vinci System enables conventionally trained urologic surgeons to perform complex minimally invasive procedures with ease and precision. Therefore, we are convinced that the system helps the urologist to adapt the whole spectrum of laparoscopic procedure in this field.

Komplexe rekonstruktive laparoskopische Operationen auf dem Gebiet der Urologie haben in den letzten 2 Jahren zunehmende Aufmerksamkeit erfahren. Zur Beherrschung dieser Operationstechniken ist jedoch ausgiebige laparoskopische Erfahrung erforderlich. Aus diesem Grunde ist es fraglich, ob diese Techniken, die sich in der Hand des Spezialisten als vorteilhaft fur den Patienten erwiesen haben, ausreichende klinische Verbreitung finden. Wir haben die moderne Computertechnologie genutzt, um die Diskrepanz zwischen offener Chirurgie und laparoskopischem Zugang zu uberbrucken und setzten das DaVinci-surgical-System ein, um in unserer Klinik die laparoskopische radikale Prostatektomie und die Pyeloplastik sowie andere retroperitoneale Eingriffe zu etablieren. Mit Hilfe des DaVinci-Systems kann sowohl die radikale Prostatektomie als auch retroperitoneale Eingriffe einfach und mit rascherer Lernkurve von der offenen Technik in laparoskopische Operationen ubersetzt werden. Es ist zu erwarten, dass in der Zukunft der urologischen Chirurgie grose Schnitte ein Relikt der Vergangenheit sein werden. Der technische Fortschritt wird uns in die Lage versetzen, bessere operative Resultate trotz minimaler Invasivitat zu erreichen.

Die Diskussion um die Geschlechterdifferenz erhielt wesentliche Anstose aus der feministischen Theoriebildung. Sie interpretierte das Mannliche in einer eher moralisch negativen Weise. Mannlichkeit muss sich standig reproduzieren und bestatigen. Fuhrend fur die mannliche Identitatsbildung ist ein konkurrenzbetontes Hegemoniestreben. Die mannliche Sozialisation fuhrt zu einer Externalisierung, die kommunikative Kompetenzen sich nur mangelhaft entwickeln lasst. Manner pflegen einen risikoreichen, den Korper instrumentalisierenden Lebensstil. Ihre Sozialisation lasst sie weniger ausgepragt Symptome als Warnsignale verstehen. Dies schlagt sich in einer geringeren durchschnittlichen Lebenszeit von Mannern gegenuber Frauen nieder. Die spezifische mannliche Sozialisation bedenkend, versucht das Frankfurter Konzept einer “Monnergesundheitsberatung” in einer “Kanzleiatmosphare” Mannern die Gelegenheit zu geben, sich anonym und kostenfrei zu allen Themen der Gesundheit des Mannes beraten zu lassen.

As the new technologies opened new routes to market, the practice of multichannel customer management has proliferated. The emergence of the Internet, for example, has pushed many established companies to expand their multichannel systems and to develop e-commerce strategies (Geyskens et al. 2002). Changing customer needs have resulted in more complex buying patterns and the use of multiple channels (Verhoef et al. 2007a). Today, consumers use different channels depending on their current purchase needs, situational factors, and the specific purchase occasion (Rangaswamy and Van Bruggen 2005). They have become accustomed to using multiple channels within the buying process and choose channels based on their specific shopping goals at a particular instance (Hutchinson and Eisenstein 2008). The Internet has revolutionized retailing with the emergence of new selling formats (e.g., digital music and movies at the Apple iTunes Store). Selling products and services online has created new possibilities for customers and businesses alike.

The first experiment was conducted in order to test hypotheses 1 to 8 concerning the basic effects of online integration on service quality, risk perceptions, and WTP as well as to derive first insights into the effects of channel integration on online purchase intentions. The analysis was conducted as an online experiment using a 2 (online integration: integrated vs. non-integrated) by 2 (purchase place: online store vs. physical store) between subjects design. A total of 308 students from the graduate and undergraduate level of the University of St.Gallen participated in the study. The sample consisted of 106 (34.6%) females and 200 (65.4%) males.

In a multichannel context, customers are very likely to be experienced and proficient in multiple channels. They choose between different channels depending on situational factors and their specific preferences in each stage of the purchase process. Each purchase channel excels in specific characteristics that make it especially suitable for certain purchase situations and product categories. Especially customers who use multiple channel formats combine the different channels according to their needs arising from a certain purchase task and their situational preferences (Montoya-Weiss et al. 2003). Thus, previous research suggests that customer service satisfaction is inherently different across online and offline channels, but not necessarily always lower online (Shankar et al. 2003).

In order to test the relationships between online integration on customer channel selection and retention, customer data was collected with two experimental studies. The respondent base consisted of the existing customers of the two cooperating firms, with firm A being the same company as in the first experiment. Both firms are described in detail in Chapters D.1.1 and D.1.2. Analogous to the previous experiment on WTP, participants were exposed to an online shop of the firms within a fictitious purchase scenario. The online shops differed in their level of integration with the firms' offline stores. Since both experiments measure purchase intentions and loyalty effects between the online and offline channel, the participants of the study were not a priori assigned to a purchase scenario in one of the two channels.

The managerial suggestions on channel integration are based on the conceptual development and the empirical findings of this work. Overall, the channel integration features tested in this study helped increase customer loyalty in online and offline channels and also had a positive effect on willingness to pay, as well as purchase intention in the online channel, while the offline channel was not significantly cannibalized. Therefore, channel integration in general, and especially integrating the online channel, may be a recommendable strategy to the multichannel system, enhance the multichannel customer experience, create customer value online, increase customer share of wallet online in the short run, and eventually across all channels in the long run. Nevertheless, due to the high costs of implementation, companies are well advised to thoroughly analyze whether channel integration is meaningful and which channels should be integrated.

The immunosuppressive effects of RIB-5/2, a nondepleting anti-rat CD4 monoclonal antibody (mAb), were analyzed in a well-defined model of accelerated cardiac allograft rejection. (LEW x BN)F1 hearts are rejected within 24 hours in LEW hosts presensitized with BN skin grafts at day -7. Treatment with RIB-5/2 mAb (3.5 mg/day i.v.) at days -7 and -1, prolonged cardiac allograft survival to the median of >62 days. The long-term recipients rejected acutely third-party (Wistar-Furth) test skin grafts, without an adverse effect on the survival of the original cardiac transplants. Lymphocytes harvested from mAb-treated hosts significantly decreased proliferative responses of donor cells in mixed leukocyte reaction. The cell activation and cytokine elaboration patterns were evaluated at the mRNA and protein levels by competitive template reverse transcriptase polymerase chain reaction and immunohistochemistry, respectively. Cardiac allografts in CD4 mAb-treated rats at 24 hours displayed reduced CD3, CD25, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-2, interferon (IFN)-gamma, and IL-10 mRNA levels as compared to those in rejecting grafts. Equal amounts of IL-4 mRNA were detected throughout in both animal groups; the expression of IL-10 mRNA increased progressively in the treated hosts. In contrast, IFN-gamma was consistently depressed after mAb therapy. The mRNA levels coding for CD3, CD25, tumor necrosis factor-alpha, IL-1-beta, and IL-2 genes were comparable in long-surviving and rejecting allografts. The staining for IL-2R, IL-2, and IFN-gamma was diminished, whereas the staining for IL-4 was either unaffected or enhanced in well-functioning grafts in RIB-5/2 mAb-treated hosts. The untreated recipients elicited strong circulating IgM allo-Ab response, which peaked around the time of cardiac rejection and then switched to IgG allo-Ab 4-7 days after heart transplantation. Treatment with RIB-5/2 mAb decreased IgM and prevented the switch into the IgG allo-Ab response. In conclusion, the ability of RIB-5/2 mAb treatment to combat accelerated rejection and to produce long-term graft acceptance is unprecedented in our experience in this model. These data provide new insights into the complexities of the cellular and humoral responsiveness, contributing to the the induction of donor-specific unresponsiveness in sensitized hosts. This study, along with our previous reports, indicate that an immune deviation in which intragraft Th1-type cytokines (primarily IFN-gamma) are diminished and Th2-type cytokines (IL-4 and IL-10) are maintained represents the common effector mechanism of CD4 mAb regimens in recipients of vascularized organ allografts.

A single intrathymic injection of donor-specific spleen cells (2x10 7 ) abrogates accelerated (24 hr) rejection of LBNF 1 cardiac allografts in presensitized LEW rats and prolongs graft survival to about 11 days. This effect is donor-specific, γ-irradiation-sensitive, thymus-dependent, and requires no concomitant therapy. We have recently shown that following intrathymic alloantigen administration, there is an earlier and increased systemic production of alloreactive IgM, and subsequently a premature isotype switching to IgG with the predominant IgG1 and IgG2a alloantibody responses. There is also a preferential binding of these IgG subclasses to the endothelium of well-functioning allografts. In this work, we analyzed the early cell activation and related cytokine elaboration patterns at the mRNA and protein levels by competitive template RT-PCR and immunohistochemistry, respectively. We found that prolonged cardiac allograft survival following intrathymic administration of donor spleen cells in presensitized rats was associated with markedly depressed intragraft IFNγ mRNA and protein expression. Moreover, intrathymic allostimulation has led to a defect in the IL-2 pathway as the expression of IL-2 and IL-2R protein at the graft site was inhibited despite stable IL-2 mRNA levels. The inhibition of cell activation was also demonstrated by reduced MHC class II and the lack of ICAM-1, and TNF-α expression by immunohistochemistry. The expression of biologically active IL-12 (p70) by mononuclear and endothelial cells was detected in rejecting grafts between 3 and 12 hr. The well-functioning grafts after intrathymic allostimulation were devoid of IL-12 (p70), which in turn may have contributed to the downregulation of IFN-γ mRNA and protein. Treatment with r-IFN-γ, but not with r.IL-2, recreated the rejection response, and the characteristic IgG subclass pattern associated with accelerated graft loss. Hence, intrathymic immunomodulation with alloantigen results in selective inhibition of IFN-γ-producing cells and a preferential upregulation of IgG1 alloantibodies. These data support the notion of the interlocked immunoregulatory roles of cytokine and alloantibody networks in rat allograft recipients.

An intrathymic injection of allogeneic spleen cells (2×10 7 ) prevents accelerated (

No immunosuppression agent is as yet available that prevents the process of chronic allograft rejection, the most critical cause of late organ allograft loss. RS61443 (mycophenolate mofetil) inhibits de novo DNA synthesis as well as diminishes expression of cell surface molecules and antibody production. As these factors seem important in the pathophysiology of the chronic phenomenon, we investigated the effects of the agent in an established model of chronic rejection of kidney allografts in a F344-to-Lewis rat strain combination. All recipients were treated for the first 10 days after engraftment with low-dose cyclosporine (1.5 mg/kg/day) to reverse an initial acute rejection episode. Since functional and morphological changes do not become manifest in this model until after 12 wk, treatment with RS61443 (15 mg/kg/day, p.o.) was either initiated at the day of grafting (Gp 1) or 8 wks thereafter (Gp 2), and continued throughout the follow-up period. Non-RS61443-treated allografted rats receiving vehicle only (Gp 3) developed progressive proteinuria after 12 wk Peak cellular infiltration (particularly macrophages in glomeruli and perivascular areas) at 16 wk was associated with densely expressed adhesion molecules (ICAM-1 on endothelium), cytokines and growth factors (TNF-α and TGF-β in glomeruli and PDGF on arterial smooth muscle cells). Interstitial fibrosis, with tubular atrophy, glomerulosclerosis, and varying degrees of intimal proliferation and luminal obliteration of vessels, progressed therafter. In vitro binding of MNC from naive animals to chronically rejecting allografted kidneys generally confirmed the immunohistological observations, peaking at 12 wk; this binding was significantly inhibited by mAbs against specific adhesion molecules (CD11a, CD18, and ICAM-1). Serum-allospecific IgG and IgM peaked at 1-2 wk after engraftment in the control recipients, decreasing thereafter. Although IgM declined to baseline after 12 wk, low levels of allospecific IgG persisted throughout the follow-up period. In contrast, recipient treatment with RS61443 (both Gp 1 and Gp 2) allowed the allografts to function normally throughout follow-up period. Proteinuria was virtually absent, and morphological and immunohistological manifestations of the chronic process were markedly diminished. In addition, treated recipients developed no significant side effects, including leukopenia, anemia, thrombopenia, nephrotoxicity, and hepatotoxicity. It appears that this agent can safely prevent the changes of chronic rejection of kidney allografts in this rat model

Purpose: To describe our technique of robotic-assisted laparoscopic radical cystectomy and intra-abdominal formation of an orthotopic neobladder (Hautmann) for treatment of transitional cell carcinoma of the bladder. Methods: We describe our surgical technique in the worldwide first attempt to perform a robotic-assisted laparoscopic radical cystectomy and completely intra-abdominal formation of an orthotopic neobladder. The DaVinci System™ (Intuitive Surgical, Mountain View, CA, USA) was utilized to perform the procedure. Results: Utilizing the DaVinci System the operation could be performed without any complications. Operating time was 8.5hours, blood loss was 200ml. The oncologic as well as the functional result of the reservoir were excellent. Discussion: We here demonstrated that sophisticated laparoscopic procedures like the intra-abdominal formation of an orthotopic neobladder are accomplishable with robotic assistance.

This study addresses the important but yet unresolved question of how firms can create competitive advantage from their multichannel marketing strategy. More specifically, the authors investigate the antecedents of channel extension strategies and their performance implications. Results from an empirical study including top managers from 308 firms indicate that in addition to environmental factors, a firm's channel expansion is directly related to its strategic channel management capability, and that this capability is more important in turbulent environments. Furthermore the study reveals that firms need an appropriate customer lock-in strategy to benefit from addition of novel channel types or traditional channel expansion.

LBNF1 cardiac allografts are rejected within 36 hr in Lewis (LEW) rats sensitized with Brown Norway (BN) skin grafts (acute rejection = 7.5 days). We analyzed the effects of intrathymic versus intravenous alloantigen challenge upon graft survival in this well-defined accelerated rejection model. Intrathymic injection of LBNF1 spleen cells (2 x 10(7)) at the time of skin transplantation (day -7) abrogated < 36 hr rejection, and prolonged the survival of cardiac allografts to about 11 days. This striking effect did not require concomitant immunosuppression, and was donor specific, as the transfer of syngeneic (LEW) or third-party (Wistar-Furth) splenocytes was ineffective. X-irradiation of donor spleen cells before inoculation restored accelerated rejection, whereas thymectomy at day -6 or 0 (the day of heart transplant) significantly shortened graft survival. In contrast, although intravenous administration of the same number of donor cells into sensitized recipients prolonged cardiac allograft survival to about 9 days, the effect was x-irradiation resistant and was never influenced by thymectomy. Radioactive tracer studies have revealed distinct trafficking patterns for the transferred cells, with those given intrathymically retained mostly in the thymus, and sequestered into host spleen and lymph nodes. Instead, intravenously injected splenocytes did not accumulate in the thymus, but were eventually trapped in the liver. Moreover, intrathymic immunomodulation has switched off cellular, rather than humoral, events at the graft site, and markedly depressed cell proliferative responses in host lymphoid organs, as analyzed by immunohistology and mixed lymphocyte response (MLR)* assay, respectively. In contrast, intravenous therapy did not have any significant effect on early intragraft cellular infiltration, including considerable neutrophil infiltration, and did not affect lymph node cell proliferation in vitro. These data document the importance of the thymus as a potential target organ for modulation of alloreactivity in vivo, and reinforce the role of distinct "central" and "peripheral" host immune mechanisms contributing to immunological unresponsiveness following organ transplantation.

Kundenbeziehungen sind heute einer der wertvollsten und gleichzeitig dauerhaftesten Wettbewerbsvorteile eines Anbieters (Tomczak/Reinecke 1998, S. 10). Da der Aufbau und Erhalt einer langfristigen Kundenbeziehung im unternehmerischen Denken und Handeln schon immer eine hohe Prioritat innehatte, stellt das Customer Relationship Management (CRM) keinen grundlegend neuen Marketingansatz dar. Konkret kann CRM als ein unternehmensweit integrierendes Fuhrungs- und Organisationsprinzip verstanden werden, das alle Masnahmen umfasst, die auf eine verbesserte Kundenorientierung und Kundenzufriedenheit gerichtet sind (Stadelmann et al. 2001, S. 6). Ubergeordnete Zielsetzung ist es, die Fahigkeiten eines Anbieters sicherzustellen, langfristig profitable Kundenbeziehungen aufzubauen (Akquisition), aufrecht zu erhalten (Bindung) und im Zeitablauf zu intensivieren (Entwicklung bzw. Penetration) (Berry 1983, S. 25).

Uber die letzten Jahre hat sich der Vertrieb uber mehrere Absatzkanale zu einem Standard im Vertrieb vieler Unternehmen in der Konsumguter-, Dienstleistungs- und Industrieguterunterbranchen entwickelt. Wenngleich verschiedene Anbieter heute vor dem Hintergrund des Internets mogliche E-Commerce-Ansatze oder aber auch Social Media- Anwendungen und damit den Einsatz mehrerer Kanale hektisch prufen bzw. planen, wird vielfach vernachlassigt, dass sich derartige Entwicklungen bereits vor mehr als 15 Jahren abzeichneten. Dementsprechend ist das Feld des Multichannel Managements nicht als ein Innovationsbereich des Marketing zu verstehen, sondern gehort vielfach schon zur „Standardklaviatur“ des Vertriebs erfolgreicher Unternehmen.

The immediate and fulminant rejection of human renal allografts in sensitized recipients was first described more than 30 years ago [1]. The process of hyperacute rejection, occurring within minutes or hours after revascularization, is thought to be primarily mediated by pre-existing anti-donor antibodies (Abs) [2]. That it has become rare in recent years is primarily ascribed to improved crossmatching techniques [3]. However, at present, over 20% of patients with end-stage renal disease on waiting transplant lists are considered highly sensitized. Apart from prior failed allografts, this may result from blood transfusions or pregnancies. These highly sensitized patients experience an increased rate of graft rejection, compared to unsensitized individuals, which is often irreversible and unresponsive to currently used immunosuppressive therapy.

Benign prostate hyperplasia (BPH) is a disease of the aging male. In BPH, the imbalance of cell proliferation and programmed cell death (apoptosis) leads to continuous stromal growth. Common medication interrupts stromal cell proliferation but has only little effect on inducing stromal cell apoptosis. In this study, we investigated tamoxifen (TAM) and 4-hydroxytamoxifen (OHT) for their ability to induce apoptosis in human prostate stromal cells (PrSC) in vitro. After the incubation of PrSC with different concentrations of TAM or OHT, the cytotoxic effect was measured using an MTT-assay. The induction of apoptosis after OHT treatment was investigated by FACS-analysis (annexin V FITC staining) and Western blot (PARP-1 cleavage, BCL-2 and BAX-alpha expression). The administration of TAM at concentrations of 0-20 microM had very little effect on cell viability as measured by MTT assay. In contrast, the use of 10-20 microM OHT led to a significant decrease in cell viability. The binding of annexin V FITC to apoptotic cells was demonstrated by FACS-analysis. The induction of apoptosis was further proven by Western blot of PARP-1 protein cleavage and the expression of the anti-apoptotic BCL-2 and the pro-apoptotic BAX-alpha proteins. In conclusion, our data clearly demonstrate, that the administration of OHT at concentrations from 10-20 microM induced apoptosis in human PrSC. The more effective induction of apoptosis with OHT compared with TAM could very well explain the results of clinical studies showing no clinical effect of TAM treatment on BPH. Furthermore, our results, if reproducible in vivo, could open new avenues for the treatment of BPH by local administration of OHT in apoptosis-inducing concentrations.

In experienced hands, laparoscopic pyeloplasty is an effective alternative treatment for symptomatic ureteropelvic junction obstruction (UPJO). Although laparoscopic surgery can clearly benefit patients, laparoscopic pyeloplasty using conventional instrumentation is complex. The purpose of this report is to evaluate the feasibility of robot assisted laparoscopic surgery. Eleven pyeloplasties for UPJO were performed via a laparoscopic transperitoneal approach exclusively with the da Vinci Surgical System. The mean procedure time was 197 min (range 110–310 min). All operations were completed laparoscopically with no intraoperative complications and negligible blood loss. All patients recovered rapidly after surgery with excellent functional results at the 1 year follow-up. Our initial experience suggests that robot assisted Anderson-Hynes pyeloplasty is a safe and effective alternative to conventional laparoscopic surgery. In our opinion, robot assisted surgery will allow urologists to perform complex procedures with greater precision, confidence, and better results, as well as enable them to adapt the whole spectrum of laparoscopic procedures to their field.

A telerobotic device, the daVinci Surgical System (Intuitive Surgical, Inc., Mountain View, CA) is one of the recently developed, remotely operated systems for laparoscopic surgical procedures. This telemanipulation system consists of two components: a control console operated by the surgeon, and the surgical arm cart that holds a three-dimensional (3-D) 30 degrees laparoscope and two detachable laparoscopic surgical tools. The instruments are equipped with a wrist--a unique feature that provides additional dexterity. Since its clinical introduction in Europe in early 1999, this system has opened up a new era in minimally invasive surgery enhancing endoscopic vision and anastomosis suturing. For the first time, cardiac surgeons were able to perform a totally endoscopic coronary bypass procedure on a beating heart.

In urology, at the end of the last millennium, there was an increasing use of computerized technology, extracorporeal shock wave lithotripsy, microwave therapy and high-energy focused ultrasound. However, experience with manipulating robots in urological surgery is still very limited. Laparoscopic surgery is handicapped by a reduction of the range of motion because of the fixed trocar position. The da Vinci system is the first surgical system to address all these problems adequately. The system consists of two main components: the surgeon's viewing and control console with three-dimensional imaging and the surgical arm unit that positions and manoeuvres detachable surgical instruments. The surgeon performs the procedure seated at the console holding specially designed instruments. Telerobotic laparoscopic radical prostatectomy provides advantages such as stereovision, dexterity and tremor filtering, but there is a learning curve with the device, mainly because of the magnification, the three-dimensional image and the lack of tactile feedback. However, after only a short period of time, the experienced surgeon is able to become familiar with the device. The impact of robotics in urological surgery is therefore very promising, and we are convinced that it will totally change the future of urological surgery.

Eine Thymus-Injektion von Donoralloantigen unter kurzzeitiger Immunsuppression fuhrt in verschiedenen MHC-inkompatiblen Transplantationsmodellen zur spezifischen Immuntoleranz [1,2]. Der Einflus einer Alloantigeninjektion auf die Transplantatabstosung in sensibilisierten Empfangern ist jedoch bisher unbekannt Diese Untersuchung analysiert die Wirkung der Alloantigengabe in den Thymus in einem wohldefinierten Modell der akzelerierten Herztransplantatabstosung in sensibilisierten Ratten [3].

Ileocystoplasty for enlargement of bladder capacity in conjunction with renal transplantation has been described in several cases. However, the surgical approach has been accomplished as a two-stage procedure. We report the case of a 21-year-old female myelomeningocele patient with end-stage renal insufficiency who was treated with ileocytstoplasty and living related renal transplantation at a single stage. Convalescence remained uneventful. On follow-up 13 months after the operation, the renal parameters remained stable.