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Background: The pilot study addresses the challenge of predicting postoperative outcomes, particularly body mass index (BMI) trajectories, following bariatric surgery. The complexity of this task makes preoperative personalized obesity treatment challenging., Objectives: To develop and validate sophisticated machine learning (ML) algorithms capable of accurately forecasting BMI reductions up to 5 years following bariatric surgery aiming to enhance planning and postoperative care. The secondary goal involves the creation of an accessible web-based calculator for healthcare professionals. This is the first article that compares these methods in BMI prediction., Setting: The study was carried out from January 2012 to December 2021 at GZOAdipositas Surgery Center, Switzerland. Preoperatively, data for 1004 patients were available. Six months postoperatively, data for 1098 patients were available. For the time points 12 months, 18 months, 2 years, 3 years, 4 years, and 5 years the following number of follow-ups were available: 971, 898, 829, 693, 589, and 453., Methods: We conducted a comprehensive retrospective review of adult patients who underwent bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy), focusing on individuals with preoperative and postoperative data. Patients with certain preoperative conditions and those lacking complete data sets were excluded. Additional exclusion criteria were patients with incomplete data or follow-up, pregnancy during the follow-up period, or preoperative BMI ≤30 kg/m 2 ., Results: This study analyzed 1104 patients, with 883 used for model training and 221 for final evaluation, the study achieved reliable predictive capabilities, as measured by root mean square error (RMSE). The RMSE values for three tasks were 2.17 (predicting next BMI value), 1.71 (predicting BMI at any future time point), and 3.49 (predicting the 5-year postoperative BMI curve). These results were showcased through a web application, enhancing clinical accessibility and decision-making., Conclusion: This study highlights the potential of ML to significantly improve bariatric surgical outcomes and overall healthcare efficiency through precise BMI predictions and personalized intervention strategies., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Severe infections during pregnancy are one of the major risk factors for cognitive impairment in the offspring. It has been suggested that maternal inflammation leads to dysfunction of cortical GABAergic interneurons that in turn underlies cognitive impairment of the affected offspring. However, the evidence comes largely from studies of adult or mature brains and how the impairment of inhibitory circuits arises upon maternal inflammation is unknown. Here we show that maternal inflammation affects multiple steps of cortical GABAergic interneuron development, i.e., proliferation of precursor cells, migration and positioning of neuroblasts, as well as neuronal maturation. Importantly, the development of distinct subtypes of cortical GABAergic interneurons was discretely impaired as a result of maternal inflammation. This translated into a reduction in cell numbers, redistribution across cortical regions and layers, and changes in morphology and cellular properties. Furthermore, selective vulnerability of GABAergic interneuron subtypes was associated with the stage of brain development. Thus, we propose that maternally derived insults have developmental stage-dependent effects, which contribute to the complex etiology of cognitive impairment in the affected offspring.

Sound information is transduced into graded receptor potential by cochlear hair cells and encoded as discrete action potentials of auditory nerve fibers. In the cochlear nucleus, auditory nerve fibers convey this information through morphologically distinct synaptic terminals onto bushy cells (BCs) and stellate cells (SCs) for processing of different sound features. With expanding use of transgenic mouse models, it is increasingly important to understand the in vivo functional development of these neurons in mice. We characterized the maturation of spontaneous and acoustically evoked activity in BCs and SCs by acquiring single-unit juxtacellular recordings between hearing onset (P12) and young adulthood (P30) of anesthetized CBA/J mice. In both cell types, hearing sensitivity and characteristic frequency (CF) range are mostly adult-like by P14, consistent with rapid maturation of the auditory periphery. In BCs, however, some physiological features like maximal firing rate, dynamic range, temporal response properties, recovery from post-stimulus depression, first spike latency (FSL) and encoding of sinusoid amplitude modulation undergo further maturation up to P18. In SCs, the development of excitatory responses is even more prolonged, indicated by a gradual increase in spontaneous and maximum firing rates up to P30. In the same cell type, broadly tuned acoustically evoked inhibition is immediately effective at hearing onset, covering the low- and high-frequency flanks of the excitatory response area. Together, these data suggest that maturation of auditory processing in the parallel ascending BC and SC streams engages distinct mechanisms at the first central synapses that may differently depend on the early auditory experience.

Amyloid beta (Aβ)-mediated synapse dysfunction and spine loss are considered to be early events in Alzheimer's disease (AD) pathogenesis. N-methyl-D-aspartate receptors (NMDARs) have previously been suggested to play a role for Amyloid beta (Aβ) toxicity. Pharmacological block of NMDAR subunits in cultured neurons and mice suggested that NMDARs containing the GluN2B subunit are necessary for Aβ-mediated changes in synapse number and function in hippocampal neurons. Interestingly, NMDARs undergo a developmental switch from GluN2B- to GluN2A-containing receptors. This indicates different functional roles of NMDARs in young mice compared to older animals. In addition, the lack of pharmacological tools to efficiently dissect the role of NMDARs containing the different subunits complicates the interpretation of their specific role. In order to address this problem and to investigate the specific role for Aβ toxicity of the distinct NMDAR subunits in dentate gyrus granule cells of adult mice, we used conditional knockout mouse lines for the subunits GluN1, GluN2A and GluN2B. Aβ-mediated changes in synaptic function and neuronal anatomy were investigated in several-months old mice with virus-mediated overproduction of Aβ and in 1-year old 5xFAD mice. We found that all three NMDAR subunits contribute to the Aβ-mediated decrease in the number of functional synapses. However, NMDARs are not required for the spine number reduction in dentate gyrus granule cells after chronic Aβ-overproduction in 5xFAD mice. Furthermore, the amplitude of synaptic and extrasynaptic NMDAR-mediated currents was reduced in dentate gyrus granule of 5xFAD mice without changes in current kinetics, suggesting that a redistribution or change in subunit composition of NMDARs does not play a role in mediating Amyloid beta (Aβ) toxicity. Our study indicates that NMDARs are involved in AD pathogenesis by compromising synapse function but not by affecting neuron morphology.

Living kidney donation is safe and established, but can lead to long-term complications such as chronic fatigue. Since the adrenal vein is usually transected during left-sided donor nephrectomy-which is not necessary on the right-we hypothesized that venous congestion might lead to an impairment of adrenal function, offering a possible explanation. In this prospective open label, monocentric cohort study, adrenal function was compared in left- and right-sided living kidney donors. The primary endpoint was plasma cortisol response to low-dose adrenocorticotropic hormone (ACTH) stimulation. Secondary endpoints included plasma renin and ACTH concentration as well as adrenal volume in response to donor nephrectomy. A total of 30 healthy donors-20 left- and 10 right-sided donations-were included. On postoperative day 1, response to low-dose ACTH stimulation was intact, but significantly lower after left-sided donor nephrectomy. After 28 days, adrenal responsiveness to ACTH stimulation did not differ any longer. Magnetic resonance imaging volumetry showed no significant adrenal volume change over 4 weeks, neither after left- nor after right-sided nephrectomy. In conclusion, left-sided living kidney donation entails a transiently reduced adrenocortical responsiveness, which returns to baseline after 28 days., (© 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

N-methyl-D-aspartate receptors (NMDARs) in all hippocampal areas play an essential role in distinct processes of memory formation as well as in sustaining cell survival of postnatally generated neurons in the dentate gyrus (DG). In contrast to the beneficial effects, over-activation of NMDARs has been implicated in many acute and chronic neurological diseases, reason why therapeutic approaches and clinical trials involving receptor blockade have been envisaged for decades. Here we employed genetically engineered mice to study the long-term effect of NMDAR ablation on selective hippocampal neuronal populations. Ablation of either GluN1 or GluN2B causes degeneration of the DG. The neuronal demise affects mature neurons specifically in the dorsal DG and is NMDAR subunit-dependent. Most importantly, the degenerative process exacerbates with increasing age of the animals. These results lead us to conclude that mature granule cells in the dorsal DG undergo neurodegeneration following NMDAR ablation in aged mouse. Thus, caution needs to be exerted when considering long-term administration of NMDAR antagonists for therapeutic purposes.

Background: In the field of anesthesia for bariatric surgery, a wide variety of recommendations exist, but a general consensus on the perioperative management of such patients is missing. We outline the perioperative experiences that we gained in the first two years after introducing a bariatric program., Methods: The perioperative approach was established together with all relevant disciplines. Pertinent topics for the anesthesiologists were; successful airway management, indications for more invasive monitoring, and the planning of the postoperative period and deposition. This retrospective analysis was approved by the local ethics committee. Data are mean [SD]., Results: 182 bariatric surgical procedures were performed (147 gastric bypass procedures (GBP; 146 (99.3%) performed laparascopically). GBP patients were 43 [10] years old, 78% female, BMI 45 [7] kg/m(2), 73% ASA physical status of 2. 42 patients (28.6%) presented with obstructive sleep apnea syndrome. 117 GBP (79.6%) patients were intubated conventionally by direct laryngoscopy (one converted to fiber-optic intubation, one aspiration of gastric contents). 32 patients (21.8%) required an arterial line, 10 patients (6.8%) a central venous line. Induction lasted 25 [16] min, the procedure itself 138 [42] min. No blood products were required. Two patients (1.4%) presented with hypothermia (<35 °C) at the end of their case. The emergence period lasted 17 [9] min. Postoperatively, 32 patients (21.8%) were transferred to the ICU (one ventilated). The other patients spent 4.1 [0.7] h in the post anesthesia care unit. 15 patients (10.2%) required take backs for surgical revision (two laparotomies)., Conclusions: The physiology and anatomy of bariatric patients demand a tailored approach from both the anesthesiologist and the perioperative team. The interaction of a multi-disciplinary team is key to achieving good outcomes and a low rate of complications., Trial Registration: DRKS00005437 (date of registration 16(th) December 2013).

Iatrogenic perforation of the upper gastrointestinal tract is one of the most serious complications of upper gastrointestinal endoscopy, with high rates of morbidity and mortality. Treatment is challenging because stent placement or surgical repair of the perforation in this area is often impossible. We report on two cases of iatrogenic perforations of the very proximal oesophagus and distal hypopharynx which could be successfully closed by using an endoluminal vacuum sponge treatment for 5 days. Thus, the endoluminal vacuum therapy may be a useful alternative to surgery in such cases of difficultly managable perforations of the upper oesophagus., (© Georg Thieme Verlag KG Stuttgart · New York.)

Clinical features, myelography, and computed tomography imaging findings as well as neurological outcome with and without surgery in 5 pug dogs with thoracolumbar arachnoid diverticula are described. Short-term prognosis after surgical therapy may not be as good as reported for other canine breeds, since immediate postsurgical deterioration is possible. Improvement of neurological deficits beyond the presurgical status may take several months.

Calcium is used throughout evolution as an intracellular signal transducer. In the mammalian central nervous system, calcium mediates the dialogue between the synapse and the nucleus that is required for transcription-dependent persistent neuronal adaptations. A role for nuclear calcium signaling in similar processes in the invertebrate brain has yet to be investigated. Here, we show by in vivo calcium imaging of adult brain neurons of the fruit fly Drosophila melanogaster, that electrical foot shocks used in olfactory avoidance conditioning evoked transient increases in cytosolic and nuclear calcium concentrations in neurons. These calcium signals were detected in Kenyon cells of the flies' mushroom bodies, which are sites of learning and memory related to smell. Acute blockade of nuclear calcium signaling during conditioning selectively and reversibly abolished the formation of long-term olfactory avoidance memory, whereas short-term, middle-term, or anesthesia-resistant olfactory memory remained unaffected. Thus, nuclear calcium signaling is required in flies for the progression of memories from labile to transcription-dependent long-lasting forms. These results identify nuclear calcium as an evolutionarily conserved signal needed in both invertebrate and vertebrate brains for transcription-dependent memory consolidation.

Autonomous learning is demonstrated by living beings that learn visual invariances during their visual experience. Standard neural network models do not show this sort of learning. On the example of face recognition in different situations we propose a learning process that separates learning of the invariance proper from learning new instances of individuals. The invariance is learned by a set of examples called model, which contains instances of all situations. New instances are compared with these on the basis of rank lists, which allow generalization across situations. The result is also implemented as a spike-time-based neural network, which is shown to be robust against disturbances. The learning capability is demonstrated by recognition experiments on a set of standard face databases., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: Vacuum phenomenon is suspected to be indicative of disc degeneration and subsequent herniation. The objective of this study was to assess the reliability of vacuum phenomenon for identification of herniated discs causing neurological signs. Prevalence of vacuum phenomenon and influencing factors in dogs with disc herniation were determined., Methods: Retrospective review of computed tomography scans from dogs with suspected disc herniation for the presence of gas within intervertebral disc space with subsequent comparison of vacuum phenomenon and herniated disc as confirmed by surgery. Subgroups were created (chondrodystrophic, non-chondrodystrophic and unknown classification) to analyse prevalence and influencing factors (age, breed and gender) for vacuum phenomenon and agreement with herniated disc., Results: Prevalence of vacuum phenomenon in all dogs, chondrodystrophic, non-chondrodystrophic dogs and those with unknown classification was 19·8, 14·9, 35·7 and 24·5%, respectively. Corresponding correlation rate between vacuum phenomenon and herniated disc was 64, 67, 40 and 82%. Prevalence of vacuum phenomenon was significantly higher in nonchondrodystrophic dogs (P=0·04). Age was the only factor influencing prevalence of vacuum phenomenon (P=0·04)., Clinical Significance: In dogs with intervertebral disc disease, vacuum phenomenon is a frequent but inconsistent finding. Although helpful to identify degenerated discs, it is not suitable to identify currently herniated disc with sufficient accuracy., (© 2013 British Small Animal Veterinary Association.)

4-Pentenols (dihomoallylic alcohols) are oxidized by cobalt(II)-activated dioxygen in solutions of dimethyl disulfide and cyclohexa-1,4-diene to afford methylsulfanyl (CH3S)-functionalized tetrahydrofurans in up to 74% yield. The reaction is a cascade, composed of oxidative alkenol cyclization providing tetrahydrofuryl-2-methyl radicals, which are trapped in dimethyl disulfide. Homolytic methylsulfanyl substitution by carbon radicals is a slow reaction, as exemplified by the rate constant of k(SCH(3)) = 3 × 10(4) M(-1) s(-1) (70 °C) derived from competition kinetics for the reaction between dimethyl disulfide and the trans-2-phenyltetrahydrofuryl-5-methyl radical. Methylsulfanyl-cyclizations therefore are experimentally performed in neat dimethyl disulfide, containing the minimum amount of cyclohexa-1,4-diene necessary for attaining almost quantitative alkenol conversion. The oxidative tetrahydrofuran synthesis occurs with noteworthy (>99%) 2,5-trans-stereoselectivity, as shown by the synthesis of diastereomerically pure 2,3- and 2,3,3-substituted 5-(methylsulfanyl)methyltetrahydrofurans from stereodefined 1,2-di- and 1,2,2-trisubstituted 4-pentenols. Changing the chemical nature of the disulfide reagent or the alkenol extends the scope of alkylsulfanyl-cyclization to ethylsulfanyl-cyclization, allylsulfanyl-transfer, or tetrahydropyran synthesis.

Alzheimer's disease is accompanied by increased brain levels of soluble amyloid-β (Aβ) oligomers. It has been suggested that oligomers directly impair synaptic function, thereby causing cognitive deficits in Alzheimer's disease patients. Recently, it has been shown that synthetic Aβ oligomers directly modulate P/Q-type calcium channels, possibly leading to excitotoxic cascades and subsequent synaptic decline. Using whole-cell recordings we studied the modulation of recombinant presynaptic calcium channels in HEK293 cells after application of a stable Aβ oligomer preparation (Aβ1-42 globulomer). Aβ globulomer shifted the half-activation voltage of P/Q-type and N-type calcium channels to more hyperpolarized values (by 11.5 and 7.5 mV). Application of non-aggregated Aβ peptides had no effect. We then analyzed the potential of calcium channel blockers to prevent Aβ globulomer-induced synaptic decline in hippocampal slice cultures. Specific block of P/Q-type or N-type calcium channels with peptide toxins completely reversed Aβ globulomer-induced deficits in glutamatergic neurotransmission. Two state-dependent low molecular weight P/Q-type and N-type calcium channel blockers also protected neurons from Aβ-induced alterations. On the contrary, inhibition of L-type calcium channels failed to reverse the deficit. Our data show that Aβ globulomer directly modulates recombinant P/Q-type and N-type calcium channels in HEK293 cells. Block of presynaptic calcium channels with both state-dependent and state-independent modulators can reverse Aβ-induced functional deficits in synaptic transmission. These findings indicate that presynaptic calcium channel blockers may be a therapeutic strategy for the treatment of Alzheimer's disease., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background and Study Aims: Double-balloon enteroscopy (DBE) has been established as an invaluable tool for the diagnosis and treatment of small-bowel diseases. To evaluate complications, procedural data, and diagnostic yield of DBE examinations in Germany the presented database was introduced., Methods: A prospective database of all DBE examinations in 62 endoscopic centers in Germany was developed using data from a standard questionnaire. Information requested included data on personal information, indications, procedural information, interventions, diagnostic yield, and complications., Results: In total, 2245 DBE examinations in 1765 patients were reported prospectively over a 2-year period. The most frequent indication was overt or occult bleeding in the small intestine and the most frequent intervention was argon plasma coagulation of angiodysplasia. The rate of complete enteroscopy was only 23 %. A clear dependency of indication and diagnostic yield could be documented, ranging widely from a diagnostic yield of 16 % in patients with abdominal pain and 82 % in patients with Peutz-Jeghers syndrome. A total of 27 complications produced a complication rate for all examinations of 1.2 %. Pancreatitis was diagnosed in four cases (0.3 % of oral-route DBE). Perforations occurred in three patients, two of whom had undergone polypectomy in the small bowel (1.5 % of 137 polypectomies)., Conclusion: DBE is a safe endoscopic technique according to this large prospective database, with a complication rate of 1.2 %. The diagnostic yield of DBE examinations depends upon the quality of indication, and is very low in patients with the single indications of "diarrhea" or "abdominal pain"., (© Georg Thieme Verlag KG Stuttgart · New York.)

Urological complications contribute to morbidity and graft loss after kidney transplantation. Aim of this study was to assess the role of revisional surgery on patient outcome. From 1997 to 2007, 887 patients underwent kidney transplantation in our institution. Clinical data of patients with urological complications were analyzed. Ureteral complications were observed in 50 of 887 (5.6%) recipients, including ureteral necrosis (0.9%), stenosis (3.6%) and ureteral reflux with recurrent graft pyelonephritis (1.1%). Thirty-five patients underwent native ureteropyelostomy, and 14 patients had redo-ureterocystostomy. All patients treated for recurrent graft pyelonephritis had no further episodes. Overall, the rate of ureteral stenosis was significantly higher after secondary surgery, compared to the primary anastomosis (10% vs. 3.6%, p = 0.039). A significantly lower incidence of graft pyelonephritis was observed in patients after native ureteropyelostomy compared to patients treated with redo-ureterocystostomy (p = 0.019). In conclusion, reflux and recurrent graft pyelonephritis can be treated effectively by secondary surgery. The use of native ureteropyelostomy may offer protection from graft pyelonephritis after secondary surgery., (© 2010 John Wiley & Sons A/S.)

Discotic molecules self-assemble into supramolecular wires that act as platforms for directed protein assembly via appended biotin functionalities.

Background: This study evaluated the prognostic impact of pretransplant donor-specific anti-human leukocyte antigen antibodies (DSA) detected by single-antigen beads and compared the three generations of crossmatch (XM) tests in kidney transplantation., Methods: Thirty-seven T-cell complement-dependent cytotoxicity crossmatch (CXM) negative living donor kidney recipients with a retrospectively positive antihuman leukocyte antigen antibody screening assay were included. A single-antigen bead test, a flow cytometry XM, and a Luminex XM (LXM) were retrospectively performed, and the results were correlated with the occurrence of antibody-mediated rejections (AMRs) and graft function., Results: We found that (1) pretransplant DSA against class I (DSA-I), but not against class II, are predictive for AMR, resulting in a sensitivity of 75% and a specificity of 90% at a level of 900 mean fluorescence intensity (MFI); (2) with increasing strength of DSA-I, the sensitivity for AMR is decreasing to 50% and the specificity is increasing to 100% at 5200 MFI; (3) the LXM for class I, but not for class II, provides a higher accuracy than the flow cytometry XM and the B-cell CXM. The specificity of all XMs is increased greatly in combination with DSA-I values more than or equal to 900 MFI., Conclusions: In sensitized recipients, the best prediction of AMR and consecutively reduced graft function is delivered by DSA-I alone at high strength or by DSA-I at low strength in combination with the LXM or CXM.

Background: Malnutrition in gastrointestinal (GI) surgery is associated with increased morbidity. Therefore, careful screening remains crucial to identify patients at risk for malnutrition and consequently postoperative complications. The aim of this study was to evaluate the ability of 3 established score systems to identify patients at risk of developing postoperative complications in GI surgery and to assess the correlation among the score systems., Methods: We evaluated prospectively 200 patients admitted for elective GI surgery using (1) nutrition risk index, (2) nutrition risk score, and (3) bioelectrical impedance analysis. Complications were assessed using a standardized complication classification. The findings of the score systems were correlated with the incidence and severity of complications. Parametric and nonparametric correlation analysis was performed among the different score systems., Results: All 3 score systems correlated significantly with the incidence and severity of postoperative complications and the duration of hospital stay. Using multiple regression analysis, only nutrition risk score and malignancy remained prognostic factors for the development of complications with odds ratios of 4.2 (P = .024) and 5.6 (P < .001), respectively. The correlation between nutrition risk score and nutrition risk index was only moderate (Pearson coefficient = 0.54). Bioelectrical impedance analysis displayed only weak to trivial correlation to the nutrition risk index (0.32) and nutrition risk score (0.19), respectively., Conclusion: The nutrition risk score, nutrition risk index, and bioimpedance analysis correlate with the incidence and severity of perioperative complications in GI surgery. The nutrition risk score was the best score in predicting patients who will develop complications in this study population. The correlation between the individual scores was only moderate, and therefore, they do not necessarily identify the same patients.

Background: One strategy to reduce the consumption of resources associated to specific procedures is to utilize clinical pathways, in which surgical care is standardized and preset by determination of perioperative in-hospital processes. The aim of this prospective study was to establish the impact of clinical pathways on costs, complication rates, and nursing activities., Method: Data was prospectively collected for 171 consecutive patients undergoing laparoscopic cholecystectomy (n = 50), open herniorrhaphy (n = 56), and laparoscopic Roux-en-Y gastric bypass (n = 65)., Results: Clinical pathways reduced the postoperative hospital stay by 28% from a mean of 6.1 to 4.4 days (p < 0.001), while the 30-day readmission rate remained unchanged (0.5% vs. 0.45%). Total mean costs per case were reduced by 25% from euro 6,390 to euro 4,800 (p < 0.001). Costs for diagnostic tests were reduced by 33% (p < 0.001). Nursing hours decreased, reducing nursing costs by 24% from euro 1,810 to euro 1,374 (p < 0.001). A trend was noted for lower postoperative complication rates in the clinical pathway group (7% vs. 14%, p = 0.07)., Conclusions: This study demonstrates clinically and economically relevant benefits for the utilization of clinical pathways with a reduction in use of all resource types, without any negative impact on the rate of complications or re-hospitalization.

Binding bacteria: Discotic molecules self-assemble into columnar supramolecular polymers that show strong polyvalent binding to bacteria by virtue of mannose ligands attached at their periphery (orange; see picture). The reversible formation of the supramolecular polymers allows simple mixing of differently substituted monomers and the optimization of bacterial aggregation.

Unlabelled: Laparoscopic gastric banding and Roux-en-Y gastric bypass are widely used for the treatment of morbid obesity. The impact of these two procedures on health-related quality of life has not been analyzed in comparative studies., Methods: A matched-pair analysis of a prospectively collected database was performed. Fifty-two consecutive patients with laparoscopic gastric bypass were randomly matched to fifty-two patients with laparoscopic gastric banding according to age, BMI, and gender. Quality of life was assessed using two standardized questionnaires (SF 36 and Moorehead-Ardelt II)., Results: Mean preoperative BMI was 45.7 kg/m(2) for the bypass patients and 45.3 kg/m(2) for the banding patients. Mean BMI after 3 years follow-up of was 30.4 kg/m(2) and 33.1 kg/m(2) (p=0.036). In the SF 36 questionnaire, gastric bypass patients yielded a mean total score of 613 versus 607 points in the gastric banding group (p=0.543), which is comparable to the normal population in Europe. In the Moorhead-Ardelt II questionnaire, the gastric bypass patients scored a mean total of 1.35 points and the gastric banding patients 1.28 points (p=0.747). Of the patients, 97% with a gastric bypass and 83% with a gastric banding were satisfied with the result of the operation (p=0.145)., Conclusion: The patients after laparoscopic gastric bypass and laparoscopic gastric banding have a high level of satisfaction 3 years after the operation and have similar quality of life scores compared to the normal population. Quality of life indexes were not different between the two procedures and were independent of weight loss in successfully operated patients.

Background: Laparoscopic splenectomy (LS) is the standard procedure for normal size or moderately enlarged spleens; open splenectomy (OS) is preferred in cases of splenomegaly. In this study, indications for and complications of open and laparoscopic splenectomy were analyzed, with the aim to identify patients who will benefit from either technique., Method: A consecutive series of 52 patients undergoing elective open or laparoscopic splenectomy between January 2001 and December 2006 was analyzed. Spleen volume was calculated as length x width x depth from the pathologist's measurements., Results: LS was performed in 25 patients with a median age of 41 years (range = 24-65). OS was performed in 27 patients with a median age of 60 years (range = 24-86) (p < 0.001). Conversion to OS was necessary in two patients (8%). Operation time was significantly shorter in LS (p < 0.05). Spleen volume was significantly greater in patients who underwent open (median = 2520 ml, range = 150-16,800 ml) versus laparoscopic (median = 648 ml, range = 150-4860 ml) splenectomy (p = 0.001). In 36% of all laparoscopic procedures, spleen volume exceeded 1000 ml. The underlying disease was mainly immunothrombocytopenia in LS patients and lymphoma and osteomyelofibrosis in OS patients. Five patients died after OS. Significantly more patients were hospitalized longer than 7 days following OS than following LS (p < 0.05). Overall complication rate was higher after OS (LS, 8; OS, 13 patients; p < 0.05)., Conclusions: LS was preferred in younger patients with moderate splenomegaly, while massive splenomegaly mostly led to OS. In view of the absence of technique-related differences, LS can primarily be attempted in all patients.

Background: Laparoscopic gastric bypass is the 'gold standard' for treatment of morbidly obese patients in many centres. There is debate regarding the optimal length for small bowel limbs. This study aimed to determine whether the proximal or distal approach is better., Methods: Twenty-five patients undergoing primary distal gastric bypass in 2000-2002 were randomly matched for age, sex and preoperative body mass index (BMI) with 25 patients having a primary proximal bypass. All distal operations were performed laparoscopically; one proximal procedure was converted to open surgery., Results: Mean operating time was 170 min for proximal and 242 min for distal bypasses (P = 0.004); median hospital stay was similar in the two groups. There were no deaths and the overall complication rate was similar, as was weight loss at 4 years: BMI decreased from 45.9 to 31.7 kg/m2 for the proximal and from 45.8 to 33.1 kg/m2 for the distal approach. Co-morbidities decreased after surgery in both groups; the prevalence of diabetes, arterial hypertension and dyslipidaemia at all time points was similar in the two groups., Conclusion: Proximal and distal laparoscopic gastric bypass operations are feasible and safe, with no differences in weight loss or reduction of co-morbidity in unselected morbidly obese patients., (Copyright (c) 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Introduction: Vertical-banded gastroplasty, a technique that is commonly performed in the treatment of morbid obesity, represents a nonadjustable restrictive procedure which reduces the volume of the upper stomach by a vertical stapler line. In addition, a textile or silicone band restricts food passage through the stomach., Case Presentation: A 71-year-old woman presented with a severe gastric stenosis 11 years after vertical gastroplasty. We describe a side-to-side gastrogastrostomy as a safe surgical procedure to restore the physiological gastric passage after failed vertical-banded gastroplasty., Conclusion: Occasionally, restrictive procedures for morbid obesity cannot be converted into an alternative bariatric procedure to maintain weight control. This report demonstrates that a side-to-side gastrogastrostomy is a feasible and safe procedure.

Background: Over the last decade, more than 130,000 laparoscopic adjustable gastric bandings (LAGB) have been performed for the treatment of morbid obesity. Nowadays, longer follow-up data are available in the literature and increasing numbers of late complications and treatment failures of gastric banding have been reported. The aim of the present study was the long-term evaluation of two different rescue operations after failed LAGB: conversion to laparoscopic Roux-en-Y bypass (LRYGB) versus laparoscopic gastric rebanding., Methods: Between January 1997 and November 2002, 74 consecutive patients underwent either laparoscopic gastric rebanding (n = 44) or LRYGB (n = 30) after failed LAGB. There were 14 men and 60 women, with a median age of 42 (23-60) years. The indication for reoperation was an increasing body mass index (BMI) and band-related complications such as pouch dilatation, band slippage, and penetration after LAGB. Rebandings were done by preference during the initial period of the study and LRYGB was the treatment of choice during the latter period. The success of the rescue operation was assessed by postoperative changes in the BMI, improvements of co-morbidities, and the need for further reoperations (secondary failure). The median follow-up was 36 months (range, 24-60 months)., Results: Patients who underwent LRYGB had a significantly better weight loss than patients with a rebanding operation (mean -6.1 versus +1.5 BMI points). In addition, the LRYGB patients showed a significantly better control of serum cholesterol during the long term follow-up (-0.6 versus +0.1 mmol/l). Almost half of the patients (45%) in the rebanding group needed a further operative revision, whereas only 20% underwent reoperation after rescue LRYGB. Thus, the secondary failure rate in the rebanding group was significantly higher compared to the bypass group (p = 0.028)., Conclusions: The present long-term study confirms our previous finding that LRYGB is a better treatment than rebanding after failed laparoscopic gastric banding regarding weight loss and treatment of co-morbidities. During the long-term follow-up the reoperation rate due to secondary failure became significantly higher in the rebanding group. We therefore recommend that LRYGB should be preferred as rescue procedure after failed laparoscopic adjustable gastric banding.

Background: Since 1994, laparoscopic Roux-en-Y gastric bypass (LRYGBP) has gained popularity for the treatment of morbid obesity. In analogy to open surgery, the operation was initially performed in a retrocolic fashion. Later, an antecolic procedure was introduced. According to short-term studies, the antecolic technique is favorable. In this study, we compared the retrocolic vs the antecolic technique with 3 years of follow-up. We hypothesized that the antecolic technique is superior to the retrocolic in terms of operation time and morbidity., Methods: 33 consecutive patients with retrocolic technique and 33 patients with antecolic technique of LRYGBP were compared, using a matched-pair analysis. Data were extracted from a prospectively collected database. The matching criteria were: BMI, age, gender and type of bypass (proximal or distal). The end-points of the study were: operation time, length of hospital stay, incidence of early and late complications, reoperation rates and weight loss in the follow-up over 36 months., Results: In the retrocolic group, operation time was 219 min compared to 188 min in the antecolic group (P = 0.036). In the retrocolic group, 3 patients (9.1%) developed an internal hernia and 4 patients (12.1%) suffered from anastomotic strictures. In the antecolic group, 2 patients (6.1%) developed internal hernias and in 3 patients (9.1%) anastomotic strictures occurred. Median hospital stay in the retrocolic group was 8 days compared to 7 days in the antecolic group. In the antecolic group, the mean BMI dropped from 46 kg/m2 to 32 kg/m2 postoperatively after 36 months. This corresponds to an excess BMI loss of 66%. In the retrocolic group, we found a similar decrease in BMI from preoperative 45 kg/m2 to 34 kg/m2 after 36 months (P = 0.276)., Conclusion: The results of our study demonstrate a reduction of operation time and hospital stay in the antecolic group compared to the retrocolic group. No differences between the two groups were found regarding morbidity and weight loss. Taken together, the antecolic seems to be superior to the retrocolic technique.

Background: A newly available, laparoscopic 5-mm bipolar vessel sealing device promises substantial advantages over the 10-mm instrument. This study compared the safety as well as the technical and surgical aspects of these different tools., Methods: For this study, 30 consecutive patients undergoing laparoscopic left-sided colectomy were prospectively randomized for the 5-mm LigaSure or The 10-mm LigaSure. The patients' demographics were analyzed together with their intraoperative and postoperative parameters, and the instruments were assessed by the surgeons with a standardized questionnaire., Results: The two groups were comparable and demonstrated similar mean operation times, blood losses, and hospital stays. The 5-mm LigaSure was applied in more operation steps and resulted in fewer bleeding episodes and less lens cleaning. Monopolar scissors were used less frequently in the 5-mm group, thus minimizing cauteric lesions and their complications (0 in the 5-mm group vs 2 in the 10-mm group). Overall satisfaction with the 5-mm LigaSure was significantly higher (8.4 +/- 0.18 vs 6.9 +/- 0.41 out of 10; p = 0.002), with significant advantages in terms of dissection capacity, visibility, and handling., Conclusion: The 5-mm LigaSure is as secure and fast as the larger 10-mm device and compares favorably in terms of finer dissection as well as trocar flexibility and handling. Therefore, it can be used safely in laparoscopic colorectal surgery.

Background: In laparoscopic Roux-en-Y gastric bypass (LRYGBP) surgery, the anastomosis between the gastric pouch and the jejunum can be performed using a circular stapler, as described in the original publication by Wittgrove in 1994. The introduction of the circular stapler through the thick abdominal wall in morbidly obese patients can be challenging. To overcome the difficulties of this task, a new device was developed and its use is presented., Method: The new device has the shape of a trocar tip which can be mounted on the circular stapler, giving it the properties of a trocar. Therefore, easier introduction into the abdominal cavity is feasible. The use of the device was assessed analyzing the data of a prospective database, comparing patient groups operated without the device (n=301) and patients operated with the device (n=100)., Results: The groups were comparable in age, sex, BMI and number of previous abdominal operations. The wound infection rate at the site of stapler introduction decreased from 6.6% to 1% (P=0.035). The overall operating time, hospital stay and complication rate were unchanged., Conclusion: The new device proved to be useful in daily practice and enabled an easier stapler introduction with fewer wound infections.

Hallmarks of the adaptive immune system are antigen-specific cellular and humoral immune responses. Secondary lymphoid organs serve as sites of contact between antigen-presenting cells (APCs) and immune effector T and B lymphocytes. The gut-associated lymphatic system (GALT) as the intestinal branch of the immune system provides different mechanisms to protect organisms against pathogens. Simultaneously, immune activation secondary to genetic factors and/or environmental signals can induce detrimental autoimmunity. The effector pathways in host defense and autoimmunity use similar cytokines and chemokines. Unlike few other cytokines, lymphotoxin (LT) alpha/beta regulates the development of intestinal lymphoid organs, including Peyer's patches (PPs) and mesenteric lymph nodes (MLNs). In addition, intestinal inflammation is suppressed by inhibition of LTbeta signalling, an observation which has initiated clinical studies using this treatment principle. Conversely, the course of Citrobacter rodentium-induced infectious colitis is more severe in mice with impaired LTbeta-receptor-mediated signalling. This report provides an overview on the role of the different organs of the GALT in intestinal inflammation. Moreover, it describes the role of the LTbeta-receptor-mediated signalling in intestinal inflammation as encountered in autoimmune and infectious pathology. The contribution of LT to the delicate balance of immune effector functions in host defense and autoimmunity is discussed.

Background: Morbidly obese patients show high somatic and psychiatric co-morbidity. Bariatric surgery is accepted as the obesity treatment with the greatest long-term success. There is growing evidence that follow-up studies should address somatic as well as psychosocial conditions of patients undergoing bariatric surgery and non-operatively treated patients. This study investigates the physical and psychosocial outcomes of patients with and without bariatric surgery., Methods: A sample of 131 morbidly obese patients applying for bariatric surgery underwent somatic and psychological assessment (T0). A first follow-up study (T1) was conducted 2 years after T0 in 119 patients. The present second follow-up (T2) was carried out 4 1/2 years after T0 and 3.2 years after potential bariatric surgery. Psychological/psychosocial measures were collected in the 93 patients, 63 of whom were treated surgically, via the Psychosocial Stress and Symptom Questionnaire (PSSQ) and a telephone interview covering BMI, employability, medication, doctor consultations, eating behavior, and physical/psychological well-being., Results: Patients with and without bariatric surgery showed a BMI reduction, which was significantly greater in those who underwent surgery (P<.001). The average percentage of excess weight loss (%EWL) between T0 and T2 was 11.5% in patients with no bariatric surgery, 36.0% in patients with laparoscopic gastric banding, and 52.8% in patients with laparoscopic gastric bypass (%EWL between T0 and T2 in patients of all groups significant, P<.001). Patients with and without surgical treatment showed significant improvement with regard to depressive symptoms and binge-eating behavior. Three-quarters of the surgically-treated and two-thirds of the non-treated patients rated their physical, psychological, and psychosocial well-being as "good" at T2., Conclusion: After 3 to 4 years, all of the patients have adapted well to their weight and body appearance, regardless of whether they have undergone surgery. Weight loss is, however, greater for operated patients, which strongly decreases the risk of developing obesity-related co-morbidities.

Gastric acid secretion is activated by two distinct pathways: a neuronal pathway via the vagus nerve and release of acetylcholine and an endocrine pathway involving gastrin and histamine. Recently, we demonstrated that activation of H(+)-K(+)-ATPase activity in parietal cells in freshly isolated rat gastric glands is modulated by the calcium-sensing receptor (CaSR). Here, we investigated if the CaSR is functionally expressed in freshly isolated gastric glands from human patients undergoing surgery and if the CaSR is influencing histamine-induced activation of H(+)-K(+)-ATPase activity. In tissue samples obtained from patients, immunohistochemistry demonstrated the expression in parietal cells of both subunits of gastric H(+)-K(+)-ATPase and the CaSR. Functional experiments using the pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein and measurement of intracellular pH changes allowed us to estimate the activity of H(+)-K(+)-ATPase in single freshly isolated human gastric glands. Under control conditions, H(+)-K(+)-ATPase activity was stimulated by histamine (100 microM) and inhibited by omeprazole (100 microM). Reduction of the extracellular divalent cation concentration (0 Mg(2+), 100 microM Ca(2+)) inactivated the CaSR and reduced histamine-induced activation of H(+)-K(+)-ATPase activity. In contrast, activation of the CaSR with the trivalent cation Gd(3+) caused activation of omeprazole-sensitive H(+)-K(+)-ATPase activity even in the absence of histamine and under conditions of low extracellular divalent cations. This stimulation was not due to release of histamine from neighbouring enterochromaffin-like cells as the stimulation persisted in the presence of the H(2) receptor antagonist cimetidine (100 microM). Furthermore, intracellular calcium measurements with fura-2 and fluo-4 showed that activation of the CaSR by Gd(3+) led to a sustained increase in intracellular Ca(2+) even under conditions of low extracellular divalent cations. These experiments demonstrate the presence of a functional CaSR in the human stomach and show that this receptor may modulate the activity of acid-secreting H(+)-K(+)-ATPase in parietal cells. Furthermore, our results show the viability of freshly isolated human gastric glands and may allow the use of this preparation for experiments investigating the physiological regulation and properties of human gastric glands in vitro.

Background: With a dramatically increasing number of bariatric operations performed world-wide in the recent years, more late complications have been noticed. Proximal gastric pouch dilatation is a known late complication after laparoscopic or open restrictive surgery for morbid obesity. In the present paper, we report our experience with laparoscopic re-operation of enlarged gastric pouches after laparoscopic gastric bypass, with emphasis on technique and outcome., Methods: Data were retrieved from a prospective database of 334 patients who underwent a laparoscopic gastric bypass operation at the University Hospital of Zurich from July 2000 to December 2004. Five laparoscopic revisions for pouch dilatation after primary bypass were performed., Results: 3 female and 2 male patients with median age 40 years (range 32-55) underwent a laparoscopic pouch resizing. At the time of the re-operation, the median BMI was 32.0 kg/m(2) (range 28.4-48.4). All procedures were performed laparoscopically with no conversion to open surgery. The median operating-time was 110 minutes (95-120). The median hospital stay was 6 days (range 5-14). The median BMI in the follow-up of 12 months (9-14) was 28.0 kg/m(2) (25.5-45.8). Diabetes mellitus improved in 4 cases during follow-up., Conclusion: Laparoscopic pouch resizing with redo of the gastro-jejunal anastomosis was feasible, safe and effective in this small series. It led to further weight loss and improved symptoms of poor pouch emptying.

Objective: To define whether laparoscopic gastric banding or laparoscopic Roux-en-Y gastric bypass represents the better approach to treat patients with morbid obesity., Summary Background Data: Two techniques, laparoscopic gastric bypass or gastric banding, are currently widely used to treat morbid obesity. Since both procedures offer certain advantages, a strong controversy exists as to which operation should be proposed to these patients. Therefore, data are urgently needed to identify the best therapy., Methods: Since randomized trials are most likely not feasible because of the highly different invasiveness and irreversibility of these procedures, a matched-pair design of a large prospectively collected database appears to be the best method. Therefore, we used our prospective database including 678 bariatric procedures performed at our institution since 1995. A total of 103 consecutive patients with laparoscopic gastric bypass were randomly matched to 103 patients with laparoscopic gastric banding according to age, body mass index, and gender., Results: Both groups were comparable regarding age, gender, body mass index, excessive weight, fat mass, and comorbidites such as diabetes, heart disease, and hypertension. Feasibility and safety: All gastric banding procedures were performed laparoscopically, and one gastric bypass operation had to be converted to an open procedure. Mean operating time was 145 minutes for gastric banding and 190 minutes for gastric bypass (P < 0.001). Hospital stay was 3.3 days for gastric banding and 8.4 days for gastric bypass. The incidence of early postoperative complications was not significantly different, but late complications were significantly more frequent in the gastric banding group (pouch dilatation). There was no mortality in both groups. Efficiency: Body mass index decreased from 48.0 to 36.8 kg/m in the gastric banding group and from 47.8 to 31.9 kg/m in the gastric bypass group within 2 years of surgery. These differences became significant from the first postoperative month until the end of the follow-up (24 months). The gastric bypass procedure achieved a significantly better reduction of comorbidities., Conclusions: Laparoscopic gastric banding and laparoscopic gastric bypass are feasible and safe. Pouch dilatations after gastric banding are responsible for more late complications compared with the gastric bypass. Laparoscopic gastric bypass offers a significant advantage regarding weight loss and reduction of comorbidities after surgery. Therefore, in our hands, laparoscopic Roux-en-Y gastric bypass appears to be the therapy of choice.

Objective: To define whether laparoscopic rebanding or Roux-en-Y gastric bypass represents the best approach for failed laparoscopic gastric banding in patients with morbid obesity., Summary Background Data: Countless laparoscopic gastric bandings have been implanted during the recent years worldwide. Despite excellent short-term results, long-term failures and complications have been reported in more than 20% of patients. Which rescue procedures should be used remains controversial. Therefore, we analyzed our experience with the use of laparoscopic rebanding versus laparoscopic Roux-en-Y gastric bypass after failed gastric banding., Methods: Using a prospectively collected database, we analyzed the feasibility, safety, and effectiveness of laparoscopic rebanding versus laparoscopic conversion to Roux-en-Y gastric bypass after failed laparoscopic gastric banding. RESULTS A total of 62 consecutive patients were treated in our institution between May 1995 and December 2002 for failed primary laparoscopic gastric banding, including 30 laparoscopic rebandings and 32 laparoscopic conversions to Roux-en-Y gastric bypass. Rebandings were preferably done during the initial period of the study and Roux-en-Y gastric bypass in the last period. Both groups were comparable before the initial banding procedures. At the time of redo surgery, patients receiving a gastric bypass had more esophageal dysmotility (47% vs. 7%, P = 0.002) and higher body mass index (BMI) than those elected for rebanding procedures (BMI 42.0 vs. 38.4 kg/m2, P = 0.015). Feasibility and safety: Each procedure was performed laparoscopically. Mean operating time was 215 minutes for gastric bypass and 173 minutes for rebanding (P = 0.03). Early complications occurred in one case in the rebanding group and in 2 cases in the bypass group; all underwent a laparoscopic reexploration without the need for open surgery. There was no mortality in this series. Effectiveness: BMI in the gastric bypass group decreased from 42.0 to 31.8 kg/m2 (P = 0.02) within 1 year of surgery, while it remained unchanged in the rebanding group., Conclusions: Laparoscopic conversion to a gastric bypass as well as laparoscopic rebanding are feasible and safe. Conversion to gastric bypass offers a significant advantage in terms of further weight loss after surgery. Therefore, this procedure should be considered as the rescue therapy of choice after a failed laparoscopic gastric banding.

Objective: The immediate hemodynamic effects of contrast agents are well documented. Less is known about their longer-lasting effects. We investigated the later effect of iopromide on the neurovascular coupling mechanism after the performance of cerebral or coronary angiography. Neurovascular coupling is a fine-tuned and reliable mechanism adapting cerebral blood flow to cortical activity. When performing a visual stimulation and measuring the resultant flow velocity change in the posterior cerebral artery transcranial Doppler has been used to determine vascular integrity., Methods: The visually evoked blood flow velocity response in the posterior cerebral artery was measured with transcranial Doppler before, 1-2 h after and the day after angiography. The overshoot of the flow velocity response and the stable flow velocity level at the end of the stimulation phase were used to compare the different conditions., Results: A significantly diminished overshoot was found 1-2 h after angiography only in patients undergoing cerebral angiography. The stable blood flow velocity levels at the end of the stimulation phase remained unchanged in all cases., Conclusions: Our finding demonstrates effects of contrast media on dynamic blood flow regulation of the cerebral vasculature 1-2 h after application of direct contrast agent suggesting a possible concentration effect of the contrast agent. However, since the relative blood flow velocity increase under stable blood flow conditions remained constant, this dynamic alteration does not cause a reduction in cerebral blood flow., (Copyright 2003 S. Karger AG, Basel)

Familial amyloidotic polyneuropathy (FAP) caused by amyloidogenic transthyretin (ATTR) mutations is the most common form of hereditary amyloidosis. We investigated the diagnostic value of the bone scanning agent technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) in this disease. Eight patients (four males, four females; age 54.4+/-8.3 years, range 43-67 years) with ATTR-FAP proven by immunohistochemistry and molecular analysis and a control group comprising ten oncological out-patients (five males, five females; age 53.4+/-8.5 years, range 34-66 years) without evidence of bony metastases were studied using 99mTc-DPD. Whole body tracer retention was 80.1%+/-10.3% (range 65.1%-94.8%) in FAP patients and 55.7%+/-8.1% (range 40.2%-66.7%) in controls at 3 h p.i. (P<0.001), and cardiac uptake was 7.3%+/-2.2% (range 4.2%-10.1%) in FAP patients and 3.1%+/-0.5% (range 2.3%-4.0%) in controls (P<0.001). The heart/whole body uptake ratio was 8.9%+/-1.7% (range 6.5%-11.0%) in FAP patients and 5.6%+/-0.5% (range 5.1%-6.8%) in controls (P<0.001). The three FAP patients with the highest cardiac tracer uptake had cardiomyopathy or arrhythmia. 99mTc-DPD scintigraphy is proposed as a simple and valuable diagnostic aid to evaluate the severity of the disease and the risk of concomitant heart problems.

Purpose: Hemoglobin levels are currently the focus of interest as prognostic factors in patients with head and neck cancer. Most published clinical trials have confirmed hemoglobin to possess a significant influence on survival in patients treated with radiotherapy. In our study we have investigated the prognostic value of hemoglobin in a combined modality schedule., Patients and Methods: Forty-three patients with advanced head and neck tumors were treated with combined radio-chemotherapy. The therapy comprised 2 courses of induction chemotherapy with ifosfamide (1,500 mg/m2, day 1 to 5) and cisplatin (60 mg/m2, day 5) followed by hyperfractionated accelerated radiotherapy with a total dose of only 30 Gy. Surgery involved tumor resection and neck dissection., Results: The 1-year overall survival rate and the 2-year survival rate were 79% and 56%, respectively. The 1- and 2-year recurrence-free survival rates were 68% and 49%, respectively. Prognostic factors with an impact on survival were seen in tumor size (T3 vs T4, p = 0.0088), response to radio-chemotherapy at the primary site (no vital tumor rest vs vital tumor rest, p = 0.045), response to lymph node radio-chemotherapy (no vital tumor cells vs vital tumor cells, p = 0.013) and level of hemoglobin after radio-chemotherapy (Hb > or = 11.5 g/dl vs < 11.5 g/dl, p = 0.0084)., Conclusion: In our study hemoglobin level after radio-chemotherapy was identified for the first time to be also a significant prognostic factor (univariate analysis) in head and neck cancer patients who underwent combined radio-chemotherapy. Besides chemotherapy plus low-dose irradiation achieved similar results in comparison with radical resection and high-dose radiotherapy at least for the first 2 years after therapy. Relapsing disease could be treated with 1 additional course of radiotherapy which is supposed to be well tolerated.

Objective: Mortality in diabetic patients with acute myocardial infarction (MI) is high. The significance of the pretreatment coronary status in type 2 diabetic patients with acute MI, as well as the effect of mechanical revascularization using percutaneous transluminal coronary angioplasty (PTCA), has not been established., Research Design and Methods: All patients with type 2 diabetes and acute MI (n = 54) were prospectively enrolled into a study of immediate coronary angiography to guide PTCA of the occluded infarct vessel. Hospital and long-term course were assessed and compared with an unselected control group of nondiabetic patients (n = 358) who were enrolled in the same study., Results: Angiography showed that sites of occlusion and acute coronary flow were similar in both groups. Multivessel disease and shock were more common in type 2 diabetic versus nondiabetic patients: 69 vs. 51% and 21 vs. 10% (P < 0.02), respectively. Direct PTCA was successful in > 90% in both groups. Mortality after 30 days was 13% in type 2 diabetic patients versus 5% in patients without diabetes (P < 0.04). Left ventricular (LV) ejection fraction before discharge was lower in diabetic patients (48 +/- 17 vs. 55 +/- 15%, P < 0.05). Mortality 1 year after discharge was 11 vs. 4% in diabetic versus nondiabetic patients (P < 0.02). Multivariate analysis identified type 2 diabetes as an independent risk factor for acute, but not for late, mortality., Conclusions: Direct PTCA is safe and effective in type 2 diabetic patients with acute MI. Mortality after 30 days in unselected diabetic patients is < 15% with this approach. Advanced disease and shock contribute to an increased mortality in type 2 diabetic patients with acute MI versus nondiabetic patients.

Silymarin can be extracted from the milk thistle, and silibinin is the main component of the plant extract. Possibly due to their antioxidant and membrane-stabilizing properties, the compounds have been shown to protect different organs and cells against a number of insults. Thus liver, kidney, erythrocytes and platelets have been protected from the toxic effects of ethanol, carbon tetrachloride, cold ischemia and drugs, respectively. The effect of silibinin on endocrine and exocrine pancreas, however, has not been studied. We therefore investigated whether silibinin treatment attenuates cyclosporin A (CiA) toxicity on rat endocrine and exocrine pancreas. Groups of 15 male Wistar rats were treated for 8 days with CiA and/or silibinin. On day 9, endocrine and exocrine pancreatic functions were tested in vitro. At the end of the treatment period, blood glucose levels in vivo were significantly higher in rats treated with CiA while silibinin did not affect glucose levels. In vitro, insulin secretion was inhibited after treatment with silibinin, but amylase secretion was not affected. After treatment with CiA both insulin and amylase secretion were reduced. Silibinin and CiA had an additive inhibitory effect on insulin secretion, but silibinin attenuated CiA-induced inhibition of amylase secretion. Despite CiA treatment, amylase secretion was in fact restored to normal with the highest dose of silibinin. Thus silibinin inhibits glucose-stimulated insulin release in vitro, while not affecting blood glucose concentration in vivo. This combination of effects could be useful in the treatment of non-insulin-dependent diabetes mellitus. Furthermore, silibinin protects the exocrine pancreas from CiA toxicity. As this inhibitory effect is probably unspecific, silibinin may also protect the exocrine pancreas against other insult principles, such as alcohol.

Somatostatin is a potent inhibitor of endocrine and exocrine pancreatic secretion. However, it is not clear whether it also inhibits pancreatic growth. Therefore we treated male Wistar rats with a somatostatin analogue, octreotide (12-192 micrograms/(kg body wt.day)), over a period of 14 days. In a dose-dependent manner, this potent and long-acting analogue caused a reduction in weight of the pancreas and a reduction in pancreatic content of protein, DNA, trypsin, chymotrypsin, amylase and lipase, as well as pancreatic content of insulin-, glucagon- and somatostatin-like immunoreactivities. When growth of rat pancreas was induced by oral administration of camostate (200 mg/(kg body wt. day) or by subcutaneous administration of cholecystokinin (2 x 10 micrograms/(kg body wt. day)) over a period of 14 days, octreotide (12-192 micrograms/(kg body wt.day)) had the same effects, but these were even more pronounced. We conclude that somatostatin is an important regulator of pancreatic growth.

It is well known that oral administration of camostate induces hyperplasia and hypertrophy of the rat pancreas. It is not clear, however, whether pancreatic hormone and enzyme secretion are affected by camostate treatment. In rats, daily administration of 200 mg camostate/kg b. wt for 14 days significantly increased pancreatic weight and pancreatic content of DNA, protein, amylase, lipase, trypsin and chymotrypsin, as well as the amount of insulin, glucagon and somatostatin. In the intact animal, blood glucose levels and serum concentrations of insulin and glucagon in response to an oral glucose load were not impaired after camostate treatment. In the isolated perfused pancreas, however, insulin and glucagon secretions were reduced, whereas somatostatin release was not affected. The volume of pancreatic juice produced by the unstimulated isolated perfused organ, as well as protein and enzyme secretion, were increased after camostate treatment. Likewise, the isolated perfused pancreas from camostate-treated rats secreted a larger volume of pancreatic juice and more protein in response to cholecystokinin (CCK), while enzyme secretion was affected in a non-parallel manner: amylase release was markedly reduced, lipase release was unchanged, and release of trypsin and chymotrypsin was increased.

Peptide YY (PYY) inhibits exocrine pancreatic secretion in several species. Two receptors, Y1 and Y2, are known to mediate PYY actions. While PYY 1-36 binds equally to both receptor subtypes, a second endogenous form of PYY, PYY 3-36, selectively activates Y2 receptors. The importance of Y receptor subtypes for inhibition of exocrine pancreatic secretion by PYY is unknown. We studied the effects of PYY 1-36 on cholecystokinin octapeptide (CCK-8)-stimulated amylase secretion in an isolated perfused rat pancreas model. To characterize functionally the receptors involved we determined the effects of a Y1-selective agonist, [Pro34]PYY; a Y2 selective agonist, PYY 3-36; and neuropeptide Y (NPY) in this model. PYY 1-36 significantly inhibited stimulated amylase secretion in the denervated rat pancreas. [Pro34]PYY and NPY both inhibited exocrine pancreatic secretion as potently as PYY 1-36. Contrary to that, the Y2 selective agonist, PYY 3-36, was inactive. We conclude that PYY inhibits exocrine pancreatic secretion in this extrinsically denervated rat pancreas model by Y1 receptors.

Intravenous glucagon inhibits exocrine pancreatic secretion in vivo, but exogenous glucagon does not affect exocrine secretion in vitro. Recent work, however, suggested that endogenous glucagon may be involved in the regulation of exocrine secretion even in vitro. We therefore investigated the effects of exogenous and endogenous glucagon on exocrine secretion by the isolated perfused rat pancreas in the presence of 1.8 mM glucose. Exogenous glucagon did not affect CCK-stimulated amylase output. 20 mM arginine stimulated glucagon release, but did not affect basal enzyme secretion. CCK-stimulated amylase output, however, was significantly inhibited in the presence of arginine. This inhibitory effect of arginine on exocrine pancreatic secretion could be blocked by glucagon antibodies, but not by nonspecific gammaglobulins. Thus exogenous glucagon failed to affect exocrine pancreatic secretion in vitro, but endogenously released glucagon or a glucagon-like peptide inhibited amylase release in the isolated perfused pancreas. We conclude that glucagon or a glucagon-like peptide may be a mediator in the islet-acinar axis.

Specific inhibitors acting upon pancreatic proteinases in the gut can cause pancreatic hypertrophy ('growth'), which is probably mediated through a feedback mechanism utilizing cholecystokinin. We have proposed the involvement of somatostatin, and here test the hypothesis that endogenous somatostatin secreted into pancreatic juice may regulate pancreatic growth. Groups of rats were given the proteinase inhibitor camostate intragastrically for either 3, 7, 14, 28, or 56 days, when they were sacrificed. In some groups the pancreata were weighed and homogenized while in other groups isolated perfused pancreatic organ preparations were performed. Somatostatin was measured in the homogenates, pancreatic juice and portal vein effluents. In camostate-fed animals, pancreatic weights increased to a maximum at 28 days, while pancreatic somatostatin content increased significantly from the third day onwards, and somatostatin secretion into pancreatic juice increased progressively until day 28. In contrast, somatostatin secretion into portal blood remained unchanged from those of untreated controls over the duration of the experiment, and its concentration was lower than in pancreatic juice. These observations provide further evidence that endogenous pancreatic somatostatin may control pancreatic growth in rats.

Cysteamine is known to deplete somatostatin from pancreatic D cells. In the isolated perfused rat pancreas we investigated its effects on somatostatin and glucagon release as well as exocrine pancreatic secretion in the presence of 1.8 mM glucose. Cysteamine, 10 mM, released somatostatin, but had no effect on CCK-stimulated amylase secretion. Arginine-stimulated glucagon release, however, was significantly inhibited by cysteamine. Concomitantly we still observed stimulation of somatostatin secretion, but also a potentiation of CCK-stimulated amylase secretion. Our results are consistent with a role of somatostatin in the regulation of exocrine pancreatic secretion via its effect on pancreatic A and B cells.