[Stressors for patients in the intensive care unit : An analysis taking controllability into consideration]. / Belastungen für Patienten auf der Intensivstation : Eine Analyse unter Berücksichtigung der Kontrollierbarkeit.

OBJECTIVE: Studies on stress factors for patients in intensive care units (ICU) have so far concentrated on whether certain stressors have occurred or how stressful they were. There are no studies on stress for patients in ICUs that measured both the perception of stress and the chances perceived to control it; however, loss of control can result in long-term psychopathological consequences, such as depression or posttraumatic stress disorder. Therefore, a questionnaire was developed to evaluate the influence of controllability on perception of stress. The aim of this study was to answer the following questions: which situations were experienced as stressful by patients in ICUs, whether patients perceived them as being controllable and whether the experience of stress depended on the controllability? Furthermore, it was examined which stressful situations are specific to ICUs. MATERIAL AND METHODS: The questionnaire included 18 potentially stressful situations for ICU patients. These situations were assessed with respect to the occurrence, frequency and duration, the impact of stress and the perception of control. In addition, anxiety was assessed using STAI-X1. A total of 198 ICU patients and 100 patients hospitalized in a general surgery ward were interviewed. RESULTS: Patients in ICUs remembered significantly more stressful situations than those on the normal ward (M ± SD = 10.2 ± 2.7 vs. 6.6 ± 2.0; d = 1.48; p < 0.001) and perceived them as more stressful (mean stress: M ± SD = 3.6 ± 1.5 vs. 2.2 ± 1.3; d = 1.01; p < 0.001). The most stressful situations for ICU patients were fixation of the arms (M ± SD = 7.47 ± 3.27), mechanical ventilation (M ± SD = 7.36 ± 3.29) and endotracheal suctioning (M ± SD = 7.19 ± 2.99). Approximately one third of patients underwent these situations. Situations experienced by more than 90% of ICU patients were evaluated as being the least stressful experiences, including infusion (M ± SD = 2.7 ± 2.7), measuring heart activity (M ± SD = 2.3 ± 2.7), taking blood samples (M ± SD = 2.2 ± 2.7), and temperature control (M ± SD = 0.9 ± 1.7). Controllability experienced by ICU patients negatively correlated with anxiety (r = -0.20, p = 0.004) and mean sensation of stress (r = -0.36; p < 0.001). When comparing stress levels of ICU patients who perceived controllability in a given situation to those who did not, the greatest effects (Cohen's d > 1.4) were observed for the situations presence of a bed barrier (M ± SD = 0.1 ± 0.4 vs. 5.9 ± 2.8), lighting at night (M ± SD = 0.7 ± 1.7 vs. 5.7 ± 3.3), presence of a ventilation tube (M ± SD = 2.5 ± 2.1 vs. 6.7 ± 3.0) and repositioning of the patient (M ± SD = 2.5 ± 2.9 vs. 6.7 ± 2.9). CONCLUSION: The experience of loss of control seems to negatively modify the impact of stressors. Thus, an increase in aspects of controllability could reduce the burden on patients during intensive care.

Color, chlorophyll a, and suspended solids effects on Secchi depth in lakes: implications for trophic state assessment.

Secchi depth (SD), a primary metric to assess trophic state, is controlled in many lakes by algal densities, measured as chlorophyll-a (chl-a) concentration. Two other optically related water quality variables also directly affect SD: non-algal suspended solids (SSNA ) and colored dissolved organic matter (CDOM, expressed as the absorption coefficient at 440 nm, a440 ). Using a database of ~1,460 samples from ~625 inland lake basins in Minnesota and two other Upper Midwest states, Wisconsin and Michigan, we analyzed relationships among these variables, with special focus on CDOM levels that influence SD values and the Minnesota SD standards used to assess eutrophication impairment of lakes. Log-transformed chl-a, total suspended solids (TSS), and SD were strongly correlated with each other; log(a440 ) had major effects on log(SD) but was only weakly correlated with log(chl-a) and log(TSS). Multiple regression models for log(SD) and 1/SD based on the three driving variables (chl-a, SSNA , and CDOM) explained ~80% of the variance in SD in the whole data set, but substantial differences in the form of the best-fit relationships were found between major ecoregions. High chl-a concentrations (> 50 µg/L) and TSS (> 20 mg/L) rarely occurred in lakes with high CDOM (a440  > ~4 m-1 ), and all lakes with a440  > 8 m-1 had SD ≤ 2.0 m despite low chl-a values (<10 µg/L) in most lakes. Further statistical analyses revealed that CDOM has significant effects on SD at a440 values > ~ 4 m-1 . Thus, SD is not an accurate trophic state metric in moderately to highly colored lakes, and Minnesota's 2-m SD criterion should not be the sole metric to assess eutrophication impairment in warm/cool-water lakes of the Northern Lakes and Forest ecoregion. More generally, trophic state assessments using SD in regions with large landscape sources of CDOM need to account for effects of CDOM on SD.

Surgical management of complicated rectovaginal fistulas and the role of omentoplasty.

BACKGROUND: Patients with rectovaginal fistulas have a significantly reduced quality of life. Therefore, surgical therapy is often needed even in palliative cases. The aim of the present study was to perform an analysis of the results of the different treatment options available today. METHODS: We performed a retrospective analysis of patients who underwent treatment for rectovaginal fistulas at the Department of Surgery, University of Schleswig-Holstein, Campus Luebeck and the Department of Surgery, WKK Heide, between January 2000 and September 2016. Complication and recurrence rate were retrospectively evaluated. The median follow-up period was 13 months (range 3-36 months). RESULTS: During the observation period, 58 patients underwent surgery (53 curative, 5 palliative) for rectovaginal fistulas. All patients who underwent curative surgery had an omentoplasty, and 39 of 53 (73.6%) patients underwent a resection. Thirty of 39 (77.0%) resections were low anterior resection, while non-continence-preserving resection included subtotal colectomy (n = 5), pelvic exenteration (n = 2), and proctectomy (n = 2). The fistulas were mainly secondary to inflammatory bowel disease (n = 18) or diverticulitis (n = 13), while 19 fistulas were a complication of different cancers or precancerous lesions. The median follow-up time was 13 months (range 6-36). Four patients (6.9%) had fistula recurrence (3 recurrences after low anterior resection, 1 after primary fistula closure). The mortality rate was 6.9% (n = 4). CONCLUSIONS: Non-resecting methods should be used only in uncomplicated fistulas. Rectovaginal fistulas secondary to inflammatory or malignant disease mostly require extensive therapy. Omentoplasty is effective for the treatment of both high and low rectovaginal fistulas.

Multi-Wavelength Photoacoustic Visualization of High Intensity Focused Ultrasound Lesions.

High intensity focused ultrasound (HIFU) thermal therapies are limited by deficiencies in existing image-guidance techniques. Previous studies using single-wavelength photoacoustic (PA) imaging have demonstrated that HIFU lesions generate contrast with respect to native tissues but have not sufficiently assessed lesion extent. The purpose of this study is to demonstrate feasibility of characterization of in vitro HIFU ablation lesion dimensions using 3D multi-wavelength PA imaging. Fresh porcine cardiac and liver tissue samples were embedded in agar phantoms and ablated using a 2.5 MHz small-animal HIFU system. Both 2D and 3D multi-wavelength photoacoustic-ultrasonic (PAUS) scans were performed in the near-infrared (NIR) range to characterize the change in the absorption spectrum of tissues following ablation and were compared to stained gross pathology to assess treatment margins and lesion extent. Comprehensive 2D multi-wavelength PA imaging yielded a spectrum in ablated tissue that did not display the characteristic local maximum in the optical absorption spectrum of deoxy-hemoglobin (Hb) near 760 nm. Two-dimensional tissue characterization map (TCM) images reconstructed from 3D TCM volumes reliably characterized lesion area and showed >70% area agreement with stained gross pathology. In addition, tissue samples were heated via water bath and concurrently interrogated with 2D PAUS imaging. PA signal exhibited an initial amplitude increase across all wavelengths, corresponding to an initial temperature increase, before then exhibiting a spectral change. This study suggests that multi-wavelength PA imaging has potential to obtain accurate characterization of HIFU lesion extent and may be better suited to guide HIFU ablation therapies during clinical treatments than single-wavelength methods.

A novel approach for the development of tiered use biological criteria for rivers and streams in an ecologically diverse landscape.

Water resource protection goals for aquatic life are often general and can result in under protection of some high quality water bodies and unattainable expectations for other water bodies. More refined aquatic life goals known as tiered aquatic life uses (TALUs) provide a framework to designate uses by setting protective goals for high quality water bodies and establishing attainable goals for water bodies altered by legally authorized legacy activities (e.g., channelization). Development of biological criteria or biocriteria typically requires identification of a set of least- or minimally-impacted reference sites that are used to establish a baseline from which goals are derived. Under a more refined system of stream types and aquatic life use goals, an adequate set of reference sites is needed to account for the natural variability of aquatic communities (e.g., landscape differences, thermal regime, and stream size). To develop sufficient datasets, Minnesota employed a reference condition approach in combination with an approach based on characterizing a stream's response to anthropogenic disturbance through development of a Biological Condition Gradient (BCG). These two approaches allowed for the creation of ecologically meaningful and consistent biocriteria within a more refined stream typology and solved issues related to small sample sizes and poor representation of minimally- or least-disturbed conditions for some stream types. Implementation of TALU biocriteria for Minnesota streams and rivers will result in consistent and protective goals that address fundamental differences among waters in terms of their potential for restoration.

[Diagnostics and therapy for neuroendocrine neoplasia of an unknown primary - a plea for open exploration]. / Diagnostik und Therapie bei neuroendokrinen Neoplasien mit unklarem Primarius - ein Plädoyer für die offene Exploration.

BACKGROUND: Neuroendocrine neoplasia (NEN) are a rare and heterogenous tumour entity. The subgroup with unknown primary tumour (N-CUP) seems to have a worse prognosis as resection of the primary is necessary for cure. The diagnostics and therapeutic algorithms for N-CUP in a German single centre are presented. PATIENTS/METHODS: Analysis of the surgical databank showed 35 cases of N-CUP in 261 cases with NEN from gastroenteropancreatic and lung origin over 2 decades (03/1990-03/2011). Three groups were built: K1 - primary detection after operative exploration (n = 10), K2 - unknown primary after operative exploration (n = 10) and K3 - no operative exploration for various reasons (n = 13). RESULTS: Initially 13.4 % (35/261) of patients presented as N-CUP, after intensified diagnostics 12.7 % (33/261) and after operative exploration 8.8 % (23/261) remained with unknown primary tumour. The sex ratio was 1 : 1, the median age is significantly higher in N-CUP [63.8 years (y) vs. 55.9 y, p = 0.004), the 5-year-survival is lower (58 vs. 72 %, n. s.). compared to NEN with known primary. Operative exploration was performed in 60.6 % (20/33), 30 % (6/20) of them were found to have inoperable situations, in 20 % (4/20) single site metastases were removed completely and in 50 % (10/20) a primary tumour was detected (8 × midgut, 2 × pancreas) intraoperatively. In these cases 70 % (7/10) got complete tumour resection (R0) and in 30 % (3/10) primary tumour resection with debulking of liver metastasis was done. In K3 (39.4 %, 13/33) most patients [69.2 % (9/13)] were treated with chemotherapy. The median age in K1 was significantly lower than in K3 (54.9 y vs. 68.3 y, p = 0.028), male dominance was seen in K3 (3,3 : 1, n. s.). The average Ki-67 index was 4.3, 23.8 and 53 % in K1, K2 and K3 (p < 0.0001 for K1 and K3 and p = 0.035 for K2 and K3), respectively. The death rate was 20, 30 and 76.9 % in K1, K2 and K3, respectively. CONCLUSION: Primary tumours of the midgut and pancreas are often found in the subset of well differentiated neuroendocrine CUP syndrome after open surgical exploration. A high rate of complete tumour resection and cure can be achieved in these cases. After common diagnostic tools (CT, MRI and somatostatin receptor scintigraphy), immunhistochemistry can give important hints (CDX-2 for midgut, TTF-1 for lung and thyroid) for a primary lesion. Also in single site metastasis without primary tumour detection a good clinical outcome is seen after complete resection.

Occurrence of waterborne pathogens and Escherichia coli at offshore drinking water intakes in lake Ontario.

The occurrence of waterborne pathogens was investigated at three drinking water intakes located about 2 km offshore in Lake Ontario. Water sampling was conducted over 3 years for Campylobacter spp., Cryptosporidium spp., Giardia spp., cultivable enteric viruses, and water quality parameters. All pathogens were detected in the offshore source water for each water treatment plant (WTP1 to WTP3), although at relatively low frequencies and concentrations. Giardia was the most common pathogen, occurring in 36% of water samples from the influent of WTP1 (n = 46), and with a maximum concentration of 0.70 cysts/liter in this influent. Cryptosporidium occurred as frequently as 15% in the WTP2 influent (n = 35), with a maximum concentration of 0.40 oocysts/liter in the WTP1 influent. The human Bacteroidales HF183 DNA marker was most common in the WTP1 influent (19%), and this was the only WTP where the Cryptosporidium hominis genotype was detected. No water quality parameter was predictive of pathogen occurrence across all three WTP influents. Escherichia coli was often below detection when pathogens were detected, and spikes in E. coli concentrations often did not coincide with pathogen occurrence. After summer rain events, river plumes had E. coli concentrations as high as 222 CFU/100 ml in surface waters 2 km offshore, without impacting drinking water intakes below the thermocline on the lake bottom. At times, prechlorination to control mussels at offshore intake cribs compromised the use of E. coli for "raw" water quality assessment, particularly for chlorine-resistant Cryptosporidium. E. coli measured by standard methods did not reliably predict pathogen occurrence at drinking water intakes in offshore ecosystems.

Transperineal omentum flap for the anatomic reconstruction of the rectovaginal space in the therapy of rectovaginal fistulas.

AIM: Deep rectovaginal fistulas are a rare entity and pose a delicate challenge for the surgeon. The present study introduces different operative interventions involved in transperineal omental flap surgery. METHOD: A retrospective analysis of all patients treated with a low or mid rectovaginal or enterovaginal fistula at the Department of Surgery of the University Hospital of Schleswig-Holstein, Campus Luebeck, was performed. Treatment results were discussed with respect to aetiology, localization, morbidity and outcome. RESULTS: Between the years 2000 and 2010, a total of nine patients with a low or mid rectovaginal fistula were treated at our clinic. After local fistulectomy, all patients were additionally treated by a laparoscopically assisted omental flap reconstruction of the rectovaginal and perineal space. Eight of the nine patients received a protective ileostomy or colostomy. Only the patient with a history of Crohn's disease had no ileostomy raised. At a median follow-up of 22 months, no patient experienced recurrence of a rectovaginal fistula. Perioperative mortality was zero and minor complications were observed in 22%. Major complications were an anastomotic insufficiency after low anterior resection that was treated without further interventions. Another complication was a persistent fistula within the sphincter that needed re-operation and bovine plug repair combined with a mucosa flap. CONCLUSIONS: Complete omental reconstruction of the rectovaginal space appears decisive in the operative therapy of deep rectovaginal or enterovaginal fistulas. Comparative studies on standard therapies are necessary although direct comparison of case series is difficult.

[Surgical treatment and prognosis of rectovaginal fistulae according to their origin]. / Chirurgische Versorgung und Prognose rektovaginaler Fisteln in Abhängigkeit ihrer Genese.

INTRODUCTION: The rectovaginal fistula is a rare entity with heterogenic causality. Its genesis seems to predict the extent of operative treatment and the prognostic outcome. The aim of this study was to present different surgical techniques in the treatment of rectovaginal fistulas and their results in correspondence to the genesis. MATERIAL AND METHODS: Between 1 / 2000 and 1 / 2010, the data of patients with rectovaginal fistulas were collected. The retrospective analysis included biographic and anamnestic data as well as clinical parameters, general and specific complications and postoperative data. RESULTS: In a timespan of ten years 36 patients with rectovaginal fistulas were treated. The most common causes were inflammatory diseases (n = 21) and earlier surgical measures (n = 6). Moreover tumour-associated fistulas (n = 5) and fistulas with unknown genesis (n = 4) were seen. As surgical techniques anterior resection (n = 21), transrectal flap plasty (n = 7), subtotal colectomy (n = 3), pelvine exenteration (n = 2) and rectal exstirpation (n = 1) were used. The closure of the vaginal lesion was performed by single suture (n = 25), flap plasty (n = 6), transvaginal omental plasty (n = 2) and posterior vaginal plasty (n = 1). All patients were provided with an omental plasty to perform a safe division of the concerned regions. Patients with a low fistula ( < 6 cm) were treated with transperineal omental plasty. The median follow-up was 12 months (6 - 36). Within this timespan 6 patients suffered from major complications [ARDS, anastomosis insufficiency, postoperative bleeding, recurrence of fistula (n = 3)]. Three patients died in the postoperative period (cerebellar infarct, septic complication associated with Crohn's disease, multiorgan failure in tumour recurrence). CONCLUSION: The genesis of rectovaginal fistulae is an important predictor for the size of resection which can range from simple excision to exenteration. For optimal therapy the surgical intervention needs to be integrated into an interdisciplinary therapy concept.

[3T-AI: a new treatment algorithm for anal incontinence with a higher evidence level]. / 3T-AI: Ein neuer, mit höherer Evidenz versehener Behandlungsalgorithmus bei analer Inkontinenz.

BACKGROUND: The evidence for conservative treatment of anal incontinence is poor. In our first publication [Schwandner et al. Dis Colon Rectum 2010; 53: 1007-1016] we demonstrated that a novel therapeutic concept, termed triple target treatment (3T), combining amplitude-modulated medium frequency stimulation and electromyography biofeedback (EMG-BF) was superior to EMG-BF alone. Questions about the required treatment duration and the relevant subgroups of patients with sphincter damage and damaged anal sensibility were not addressed. METHODS: We enrolled 158 patients with anal incontinence in this randomized study. Here, we -report on the important subgroup analyses of patients with and without sphincter damage and damaged anal sensibility for the endpoints Cleveland Clinic Score (CCS) and success record. Using the results of this study we propose a novel treatment algorithm which is open for discussion. RESULTS: In patients with sphincter damage, the median difference on the CCS from baseline to 9 months was 5 points higher for 3T than for EMG-BF (95 % confidence interval 0-8; p = 0.0168). While 47 % of the patients with sphincter damage became continent with 3T, only 18 % did with EMG-BF (p = 0.0036). Ten of 17 patients in the 3T group regained anal sensibility after 3 months stimulation. There was tendency towards improved continence in patients with neuropathy upon 3T treatment (p = 0.1219). CONCLUSIONS: 3T is superior to EMG-BF alone for patients with sphincter damage and neuropathic anal incontinence. It is a successful key element within our treatment algorithm, even in patients with sphincter damage and neuropathic anal incontinence.

Chironomus gelhausi, a new species of surface-mating Chironomus Meigen, 1803 (Diptera: Chironomidae) from Mongolia.

The adult male and female of Chironomus gelhausi n. sp. are described from a small lake in western Mongolia. Based on field observations and morphological characters, C. gelhausi is a surface-mating species which has retained the ability to fly. Morphological characteristics associated with surface-mating in this species include apically truncated wings, reduced antennal plume in the male, reduced palps, reduced mid and hind leg length, and enlarged hypopygium. Behavioral observations and morphology of C. gelhausi indicate that this species is a species of Chironomus which has independently evolved morphological characteristics consistent with surface-mating behavior similar to that of Fleuria and other species within Chironomus sensu lato. We can assume that this behavior and the associated morphological characteristics are related to survival in a harsh environment where high winds could displace aerial mating swarms from the larval habitat.

False recognition in Lewy-body disease and frontotemporal dementia.

The primary goal of this study was to evaluate the false recognition phenomenon in persons with frontotemporal dementia (FTD) and those with Lewy-body disease (LBD). Patients with LBD (n=10) or FTD (n=15) and their corresponding controls (n=30) were subjected to the Deese-Roediger-McDermott (DRM) paradigm to induce false recognition. Patients were first presented with items semantically related to a nonpresented critical target. The critical target was later included in a word list shown to patients to assess level of recognition. Both groups of patients showed a reduced level of false recognition of the critical target when controlling for their overall level of false alarms. This reduction was greater in persons with LBD than in those with FTD. Correlational analyses of performance on neuropsychological tests and the DRM variables indicated that the reduced DRM effect was associated with inhibition deficits in patients with LBD and with inhibition deficits and verbal memory in those with FTD. Our results support current models suggesting that these cognitive components contribute to the false recognition effect.

[Impact of preoperative patient education on postoperative pain in consideration of the individual coping style]. / Einfluss präoperativer patienteninformationen auf postoperative schmerzen unter berücksichtigung individueller stressverarbeitung.

OBJECTIVE: the German guideline for the treatment of acute perioperative and post-traumatic pain (S3-Leitlinie zur Behandlung akuter perioperativer und posttraumatischer Schmerzen) recommends giving preoperative information about postoperative pain and how to influence it. It is expected that the effect of preoperative information is modified by psychological characteristics of the patient. One of these psychological characteristics is the individual coping style. The purpose of the study is to evaluate whether or not patients benefit from preoperative education in relation to their level of negative coping style. METHODS: the study is based on a 2×2 factorial experimental design with the experimental factor "treatment" (education vs control condition) and the factor "negative coping style" (high vs low). After informed consent 96 patients undergoing abdominal or vascular surgery were enrolled in the study. Outcomes were pain intensity, pain quality and psychic state. They were assessed by using numerical rating scales and psychometric methods of self-assessment. The data were collected preoperatively and on the first to third postoperative day. RESULTS: patients who received preoperative education experience a greater reduction in postoperative pain than patients without preoperative education do (ES=0.48). The risk for stronger pain (NRS>3) on the third postoperative day is decreased (2.1 vs 14.6%). The influence of negative coping style is altogether minimal. CONCLUSIONS: preoperative patient information has positive effects on the postoperative development of pain. Patient information is a valuable addition to the drug pain treatment. The application can be recommended regardless of the level of the patients' negative coping style.

Winter growth, development, and emergence of Diamesa mendotae (Diptera: Chironomidae) in Minnesota streams.

Diamesa mendotae Muttkowski is commonly observed emerging during winter at low air temperatures from Minnesota streams, but little is known about the winter dynamics of this and other winter-emerging aquatic insects. Biweekly collections of surface-floating pupal exuviae indicated that this species emerged from October through May, when water temperatures were less than approximately 10 degrees C. Emergence occurred continuously through winter, with a lull during January and February. Development of larvae from in situ growth enclosures supported emergence data and indicated that the reduction and halt of emergence in the spring was related to increasing water temperatures (> 10 degrees C), which were unsuitable for the growth or survival of the larvae. Development continued through January when water temperatures were at their lowest for the study stream and therefore did not explain the mid-winter lull in emergence. Growth rates of D. mendotae were not greater than other chironomid taxa at similar temperatures, indicating that lower critical thermal limits for growth allow this species to dominate ground-water influenced streams during the winter in Minnesota. The results of this study show that D. mendotae is well suited for growth and development at low temperatures and provides an assessment of important factors that regulate this species at low water and air temperatures.

[Does the third staple line of a new endostapler offer an advantage?]. / Bringt die dritte Klammernahtreihe eines neuen Endostaplers einen medizinischen Vorteil?

BACKGROUND: In laparoscopic colon surgery, endostaplers generate 2 parallel rows of staples. The aim of this paper is to analyse whether the introduction of a new endostapler generating a third row of staples influences the rate of anastomotic leakage and bleedings. METHOD: 362 patients of the Department of Surgery, University Clinic of Schleswig-Holstein, Campus Lübeck, were included in this study. All patients underwent colon resection with performance of double-stapling anastomosis. In Group I (n = 148; 7 / 2004 to 12 / 2005), the Endopath TSB 45 endostapler (2 rows of staples) was used, whereas in Group II (n = 214; 7 / 2006 to 12 / 2007), the Echelon60 EC60 stapler (3 rows of staples) was used. All further operational steps were identical for both groups. Target parameters were the postoperative anastomotic leakage and anastomotic bleeding rates. RESULTS: Between July 2004 and December 2005, the number of anastomotic leaks (Stapler Endopath, TSB 45) was n = 4 (2.7 %), for the second period (Stapler Echelon60 EC60), it was n = 9 (3.7 %) (not significant). Using the Endopath TSB 45 stapler, the number of anastomotic bleedings was n = 12 (8.1 %), and for the Echelon60 EC60 stapler, it was n = 8 (3.7 %) (p = 0.074; not significant). Within the 18-month period between July 2006 and December 2007, the number of endoscopic colon operations (n = 214) rose by 44.6 % compared to the 18-month period between July 2004 and December 2005 (n = 148). CONCLUSION: The application of the advanced Echelon endostapler has no impact on the number of anastomotic leaks, and reduces the number of anastomotic bleedings slightly but not significantly. The increased number of endoscopic procedures in the second period results both from the growing number of indications for the application of endoscopic techniques and the positive findings of recent studies carried out by our own and other working groups.

[Progress in diagnostics of anorectal disorders. Part II: radiology]. / Fortschritte in der Diagnostik anorektaler Erkrankungen. Teil II: Radiologische Verfahren.

Diagnostics and therapy of anorectal disorders remain a surgical question. In close cooperation between different departments (radiology and gastroenterology, urology and gynecology, dermatology and psychology), the role of radiologic imaging is of growing importance. Exact knowledge of functional anatomy and precise clinical examination constitute the basis of the according therapeutic strategies. In this context radiology has contributed decisively. Developments in imaging techniques, e.g. dynamic MRI, highly contributed to better understanding of complex functional pelvic floor disorders. The combination of nanotechnology and high-resolution imaging allows precise staging, especially in rectal cancer. Furthermore, advances in virtual colonoscopy could lead to widely acceptable and patient-friendly screening for colorectal malignancies.

[Progress in diagnostics of anorectal disorders. Part I: anatomic background and clinical and neurologic procedures]. / Fortschritte in der Diagnostik anorektaler Erkrankungen. Teil I: Anatomische Grundlagen sowie klinische und neurologische Verfahren.

Diagnostics and therapy of anorectal disorders are still questions of surgery. Exact knowledge of functional anatomy and precise clinical examination constitute the basis for the resulting therapeutic strategies. Three-dimensional endosonography and technical advances in flexible endoscopy using high-resolution chromoendoscopy and narrow-band imaging enable exact staging and diagnosis, even of malignancies in earliest stages. Furthermore new in-vivo staining methods combined with high-resolution imaging facilitate the discrimination of inflammatory and neoplastic lesions, which often lead to diagnostic difficulties in chronic inflammatory bowel disease. Developments in neurologic testing, including surface electromyography and sacral nerve stimulation, complement the diagnostic armamentarium.

Adhesion-related kinase induction of migration requires phosphatidylinositol-3-kinase and ras stimulation of rac activity in immortalized gonadotropin-releasing hormone neuronal cells.

GnRH neurons migrate into the hypothalamus during development. Although migratory defects may result in disordered activation of the reproductive axis and lead to delayed or absent sexual maturation, specific factors regulating GnRH neuronal migration remain largely unknown. The receptor tyrosine kinase, adhesion-related kinase (Ark) (also known as Axl, UFO, and Tyro7), has been implicated in the migration of GnRH neuronal cells. Binding of its ligand, growth arrest-specific gene 6 (Gas6), promotes cytoskeletal remodeling and migration of NLT GnRH neuronal cells via Rac and p38 MAPK. Here, we examined the Axl effectors proximal to Rac in the signaling pathway. Gas6/Axl-induced lamellipodia formation and migration were blocked after phosphatidylinositol-3-kinase (PI3K) inhibition in GnRH neuronal cells. The p85 subunit of PI3K coimmunoprecipitated with Axl and was phosphorylated in a Gas6-sensitive manner. In addition, PI3K inhibition in GnRH neuronal cells diminished Gas6-induced Rac activation. Exogenous expression of a dominant-negative form of Ras also decreased GnRH neuronal lamellipodia formation, migration, and Rac activation. PI3K inhibition blocked Ras in addition to Rac activation and migration. In contrast, pharmacological blockade of the phospholipase C gamma effectors, protein kinase C or calcium/calmodulin protein kinase II, had no effect on Gas6/Axl signaling to promote Rac activation or stimulate cytoskeletal reorganization and migration. Together, these data show that the PI3K-Ras pathway is a major mediator of Axl actions upstream of Rac to induce GnRH neuronal cell migration.

Possible association of the pro-melanin-concentrating hormone gene with a greater body mass index as a side effect of the antipsychotic olanzapine.

Following our report of a linkage at 12q24 with a phenotype of obesity under antipsychotics, we tested the pro-melanin-concentrating hormone (PMCH) candidate gene for a possible association in humans with the body mass index (BMI; kg/m2) in unrelated schizophrenic patients (SZ) receiving antipsychotics (N = 300) and in controls (CTL; N = 150). Subjects were classified in obese (OB) (BMI > or = 30 kg/m2), overweight (25 < or = BMI < 30 kg/m2), and normal weight (BMI < 25 kg/m2) groups. Single nucleotide polymorphisms (SNP) rs7973796 and rs11111201, located 5' at -4.5 kb and 3' at +1.8 kb, respectively, of PMCH were genotyped. Interaction effects of genotypes and antipsychotic treatment on BMI were tested in a covariance analysis with age and gender as covariates. Interaction effects on the prevalence of obesity were tested in a logistic regression analysis. For subjects under 50 years, the effect of the rs7973796 genotype on BMI differed between the SZ patients taking olanzapine and CTL group (interaction P = 0.025). Olanzapine-treated SZ patients carrying the ancestral homozygote genotype showed a higher BMI for rs7973796 (P = 0.016 with the LSMeans t-test) than the variant homozygotes. Accordingly, the ORs for obesity associated with rs7973796 genotypes differed in the SZ patients taking olanzapine compared to the CTL group (interaction P = 0.0094). The G allele was associated with an increase in the odds of obesity in SZ patients taking olanzapine. No association was observed for those over 50 years, or for rs11111201. These results suggest that the common allele of PMCH rs7973796 may be associated with a greater BMI in olanzapine-treated SZ patients.