ASGE guideline on the role of endoscopy in the management of benign and malignant gastroduodenal obstruction

This American Society for Gastrointestinal Endoscopy guideline provides evidence-based recommendations for the endoscopic management of gastric outlet obstruction (GOO). We applied the Grading of Recommendations, Assessment, Development and Evaluation methodology to address key clinical questions. These include the comparison of (1) surgical gastrojejunostomy to the placement of self-expandable metallic stents (SEMS) for malignant GOO, (2) covered versus uncovered SEMS for malignant GOO, and (3) endoscopic and surgical interventions for the management of benign GOO. Recommendations provided in this document were founded on the certainty of the evidence, balance of benefits and harms, considerations of patient and caregiver preferences, resource utilization, and cost-effectiveness.

Electrical cell-substrate impedance sensing with field-effect transistors is able to unravel cellular adhesion and detachment processes on a single cell level.

We introduce a novel technique of impedimetric sensing of cellular adhesion, which might have the potential to supplement the well-known technique of Electrical Cell-substrate Impedance Sensing (ECIS) in cell culture assays. In contrast to the already commercialized ECIS method, we are using ion-sensitive field-effect transistor (ISFET) devices. The standard gold microelectrode size in ECIS is in the range of 100-250 µm in diameter. Reason for this limitation is that when downscaling the sensing electrodes, their effective impedance governed by the metal-liquid interface impedance is becoming very large and hence the currents to be measured are becoming very small reaching the limit of standard instrumentation. This is the main reason why typical assays with ECIS are focusing on applications like cell-cell junctions in confluent cultures. Single cell resolution is barely reachable with these systems. Here we use impedance spectroscopy with ISFET devices having gate dimensions of only 16 × 2 µm(2), which is enabling a real single cell resolution. We introduce an electrically equivalent circuit model, explain the measured effects upon single cell detachment, and present different cellular detachment scenarios. Our approach might supplement the field of ECIS with an alternative tool opening up a route for novel cell-substrate impedance sensing assays with so far unreachable lateral resolution.

Neurodegeneration through oxidative stress: monitoring hydrogen peroxide induced apoptosis in primary cells from the subventricular zone of BALB/c mice using field-effect transistors.

Dementia is one of the big medical challenges of our time with Alzheimer's, Huntington's and Parkinson's disease among its most common forms. In year 2000, 4.5 million people were diagnosed with Alzheimer's disease in the United States. In the case of Alzheimer's disease one of many contributing factors is a metabolic imbalance that leads to elevated oxidative stress levels. Consequences of this imbalance can be symptoms like apraxia, agnosia or sundowning. The use of field-effect transistors is a novel approach to study the effects of external stimuli on cells in vitro to provide researchers with a new tool for high resolution and high throughput studies to better understand cellular interaction and the effects of pharmacological compounds. In our study we use ion-sensitive field-effect transistors (FETs) to analyze the apoptosis inducing effects of hydrogen peroxide treatment on primary cells obtained from the subventricular zone of postnatal BALB/c mice. Upon apoptosis, the cell-substrate adhesion of the neurons is gradually weakened until complete detachment. In former studies we used our FET devices to conduct Electrical Cell-substrate Impedance Sensing (ECIS) experiments on the single cell level using morphologically different cell lines. Here we demonstrate that our novel approach of ECIS using FET devices can be expanded to primary neuronal tissue with high prospects for further studies in the field of pharmacological research.

The significance of chloride in the inhibitory action of disodium cromoglycate on immunologically-stimulated rat peritoneal mast cells.

BACKGROUND: The microelectrode array (MEA) was used to investigate the pharmacological relevance of chloride (Cl-) ions in antigen-dependent mast cell activation and the inhibitory effect of disodium cromoglycate (DSCG) on mast cell activation. METHODS: The movements of ions across the cellular membrane and the potential relationship between Cl- channels and DSCG during immunological activation were investigated using the MEA. The results were then subsequently compared with the amount of histamine released from anti-IgE activated peritoneal mast cells. RESULTS: The inclusion of charybdotoxin (ChTX) in Cl--free buffer showed that the measured field potentials during antigen-stimulated peritoneal mast cell were a combination of Cl- influx and K+ efflux. The delayed onset time of Cl- influx indicated the presence of a delayed outwardly-rectifying Cl- current in the antigen-stimulated peritoneal mast cells. The use of 5-nitro-2-(3-phenylpropylamino) benzoic acid demonstrated that the activated mast cell membrane potential can be stabilised, thereby reducing the amount of histamine released from the anti-IgE activated mast cells. The correlation between the results of the histamine release assay and the electrophysiological measurements demonstrated the importance of Cl- to anti-IgE dependent mast cell activation. The inhibitory effect of DSCG on anti-IgE activated cells, however, did not correlate with the presumed influx of Cl-. CONCLUSIONS: The MEA data suggest that Cl- influx is crucial to IgE-dependent mast cell degranulation. GENERAL SIGNIFICANCE: While the MEA cannot yield information about single channel properties, it is convenient to use and can provide information on the global changes in electrophysiological responses of non-excitable cells.

Onset patterns prior to 36 months in autism spectrum disorders.

The present study investigated differences among children with three different patterns of autism symptom onset: regression, plateau, and no loss and no plateau. Cross-sectional data were collected from parents of children aged 3-17 years with an autism spectrum disorder (n = 2,720) who were recruited through a US-based online research database. Parental report of developmental characteristics was assessed through a parent questionnaire, and current autism symptoms were measured via the Social Responsiveness Scale and Social Communication Questionnaire. Multivariate analyses indicated that children with regression had a distinct developmental pattern marked by less delayed early development. However, following regression, these children evinced elevated autism symptom scores and an increased risk for poorer outcomes when compared with the other onset groups.

All that bleeds is not infliximab-refractory ulcerative colitis.

The role of biological agents in moderate to severe ulcerative colitis has been shown to be effective in the induction of clinical remission. However, the role of infliximab therapy for induction of remission in patients with fulminant colitis is debatable. A case of a hospitalized patient with a new diagnosis of severe ulcerative colitis refractory to intravenous steroids is presented. The patient was treated with infliximab and discharged with clinical remission, but subsequently presented back to hospital with a lower gastrointestinal hemorrhage.

The use of microelectrode array (MEA) to study the protective effects of potassium channel openers on metabolically compromised HL-1 cardiomyocytes.

The microelectrode array (MEA) was used to evaluate the cardioprotective effects of adenosine triphosphate sensitive potassium (K(ATP)) channel activation using potassium channel openers (KCOs) on HL-1 cardiomyocytes subjected to acute chemically induced metabolic inhibition. Beat frequency and extracellular action potential (exAP) amplitude were measured in the presence of metabolic inhibitors (sodium azide (NaN(3)) or 2-deoxyglucose (2-DG)) or KCOs (pinacidil (PIN, a cyanoguanidine derivative, activates sarcolemmal K(ATP) channels) or SDZ PCO400 (SDZ, a benzopyran derivative, activates mitochondrial K(ATP) channels)). The protective effects of these KCOs on metabolically inhibited HL-1 cells were subsequently investigated. Signal shapes indicated that NaN(3) and 2-DG reduced the rate of the sodium (Na(+)) influx signal as reflected by a reduction in beat frequency. PIN and SDZ appeared to reduce both rate of depolarization and extent of the Na(+) influx signals. Pre-treating cardiomyocytes with PIN (0.1 mM), but not SDZ, prevented the reduction of beat frequency associated with NaN(3)- or 2-DG-induced metabolic inhibition. The exAP amplitude was not affected by either KCO. The cardioprotective effect of PIN relative to SDZ may be due to the opening of different K(ATP) channels. This metabolic inhibition model on the MEA may provide a stable platform for the study of cardiac pathophysiology in the future.

The use of infliximab for treatment of hospitalized patients with acute severe ulcerative colitis.

BACKGROUND/AIM: The use of infliximab in severe ulcerative colitis (UC) is established; however, its role in severe acute UC requires clarification. The present multicentre case series evaluated infliximab in hospitalized patients with steroid-refractory severe UC. METHODS: Patients from six hospitals were retrospectively evaluated. Data collection included demographics, duration of disease and previous treatments. The primary end point was response to in-hospital infliximab; defined as discharge without colectomy. RESULTS: Twenty-one patients (median age 26 years) were admitted between May 2006 and May 2008 with severe UC requiring intravenous steroids and given infliximab (median time to infusion eight days). Sixteen (76%) patients were discharged home without colectomy; three of these underwent colectomy at a later date. Of the remaining 13 patients (62%), all but two did not require further courses of steroids; six patients had infliximab as a bridge to azathioprine and seven patients were maintained on regular infliximab. Five patients required in-hospital colectomy after the initial infliximab. CONCLUSIONS: In this real-life experience of infliximab in patients with steroid-refractory severe UC, infliximab appears to be a viable rescue therapy. The majority of patients were discharged without surgery and 62% maintained response either as a bridge to azathioprine or maintenance infliximab.

Inhibitors of tripeptidyl peptidase II. 2. Generation of the first novel lead inhibitor of cholecystokinin-8-inactivating peptidase: a strategy for the design of peptidase inhibitors.

The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase which has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to give Asp-Tyr(SO(3)H)-Met-OH + Gly-Trp-Met-Asp-Phe-NH(2). In seeking a reversible inhibitor of this peptidase, the enzymatic binding subsites were characterized using a fluorimetric assay based on the hydrolysis of the artificial substrate Ala-Ala-Phe-amidomethylcoumarin. A series of di- and tripeptides having various alkyl or aryl side chains was studied to determine the accessible volume for binding and to probe the potential for hydrophobic interactions. From this initial study the tripeptides Ile-Pro-Ile-OH (K(i) = 1 microM) and Ala-Pro-Ala-OH (K(i) = 3 microM) and dipeptide amide Val-Nvl-NHBu (K(i) = 3 microM) emerged as leads. Comparison of these structures led to the synthesis of Val-Pro-NHBu (K(i) = 0.57 microM) which served for later optimization in the design of butabindide, a potent reversible competitive and selective inhibitor of the CCK-8-inactivating peptidase. The strategy for this work is explicitly described since it illustrates a possible general approach for peptidase inhibitor design.

Prevalence of Onchocerca volvulus nodules in the Sankuru River Valley, Democratic Republic of the Congo, and reliability of verbal assessment as a method for determining prevalence.

The epidemiology of onchocerciasis in much of the Democratic Republic of the Congo (formerly Zaire) is not well established. We report the results of an onchocerciasis rapid assessment survey carried out in 18 villages of the Sankuru River Valley in the central part of this country in preparation for mass distribution of ivermectin. Thirty men from each village were randomly selected and examined for subcutaneous nodules. The prevalence of nodules among these men in each village ranged from 82.5% to 100% with a mean prevalence of 95.0%. This study also assessed the validity of using verbal assessment instead of physical examination to determine prevalence of nodules. This verbal method had a sensitivity of 93.5% and a specificity of 83.3%. High sensitivity and specificity for this method suggest that it might be a cost-effective approach to determine the prevalence of onchocerciasis over large areas without using physical examinations requiring medical personal. This approach could be particularly useful where the coverage of health services is poor. The use of the Global Positioning System made it possible to send coordinates and survey data electronically to World Health Organization personnel in Geneva for computer generation of prevalence maps. The use of river boats to conduct surveys and support ivermectin distribution in the Congo is discussed.

A medical audit and patient survey of hysterectomies performed for menstrual disorders.

The aim of the study was to carry out an audit of 283 hysterectomies performed for menstrual disorders over a one year period, and to determine the satisfaction of the women concerned towards their treatment. The medical records of these patients were examined, and they were each sent a questionnaire, 69% of which were completed and returned. The most common presenting symptoms were menorrhagia and dysmenorrhoea. In 53% of cases no clinical abnormality was postulated and in 31% of cases no pathological abnormality was found. The preoperative clinical and pathological diagnoses were in agreement for 59% of patients. Over 90% of women were satisfied with the management of their case by their GP and the gynaecology outpatient clinic. The use of patient-controlled analgesia systems was associated with better post-operative pain relief than intramuscular injections. Thirteen percent of patients required blood transfusion; 21% suffered some form of postoperative complication, most of which were minor. Ninety-four percent of the women were pleased that they had undergone hysterectomy, and 76% wished that they had had the operation sooner. It was concluded that hysterectomy is perceived positively by patients and should not necessarily be considered as a last resort treatment for menstrual disorders.

An evaluation of purified reconstituted type 1 collagen fibers.

Collagen fibers composed of type I collagen molecules were studied for biocompatibility and mechanical properties. These fibers were crosslinked using two different processes: 1) glutaraldehyde, 2) dehydration followed by exposure to cyanamide (DHT/C); the latter method produces only urea as a by-product of the crosslinking process and is postulated to be more biocompatible. An in vitro model using rat tendon fibroblasts growing on individual fibers was used to evaluate outgrowth rates, cell/fiber interactions, and cell morphology. These studies showed an advantage with DHT/C crosslinking, relative to glutaraldehyde crosslinking, in promoting fibroblast growth. In vivo intramuscular implantation in rats showed excellent biocompatibility for both kinds of collagen implants. In addition, aligned ingrowth into the implant from the medial collateral ligament when applied in that location was demonstrated. Mechanical testing demonstrated the higher strength of dry fibers; however, upon hydration, there was a marked decrease in stress to failure. This reduction in strength was due principally to an increase in cross section due to swelling. These collagen fibers appear to be very biocompatible even in the presence of low concentrations of glutaraldehyde. They promote fibrous aligned ingrowth in a setting of ligament healing. Thus, they represent a strong candidate as a scaffold ligament or tendon prosthesis if crosslink density can be increased.

Autotransfusion in revision total hip arthroplasties using uncemented prostheses.

During the period from March 1983 to April 1987, autotransfusion was used in 64 patients treated with cementless revision total hip arthroplasties. An average of 3.9 units of intraoperative blood was salvaged, using a semicontinuous system; 6.5 units were salvaged in patients requiring segmental grafting of the acetabulum and femur. Patients not requiring segmental grafting had only 2.1 units salvaged. The use of homologous banked blood in patients without stored autologous units available was almost three times that of patients with autologous blood. Autotransfusion in the form of autologous transfusions and intraoperative blood salvage accounted for 72% of the total blood requirements. The cell saver is most cost-effective in patients with femur and acetabular bone loss requiring segmental grafting. An autologous transfusion program is important in all patients in whom blood transfusions are expected.

Trauma operating room in conjunction with an air ambulance system: indications, interventions, and outcomes.

We report a retrospective study of 198 trauma patients brought directly to a trauma operating room by an air ambulance system. Despite rapid transport, expert prehospital resuscitation, and the capability of early surgical intervention, the overall mortality was high (57%). There was no significant salvage of patients arriving without pulse, blood pressure or cardiac activity. Optimal trauma care failed to show encouraging results in this preselected group of patients with predominantly blunt and multisystem injury. The justification and cost effectiveness of this system of trauma care is discussed.