bluuebunny/crossref_metadata_2025 huggingface dataset:
Pseudomembranous Colitis: An Update
Authors: Brar Harpreet S , Surawicz Christina M
Published: April 2016

Clostridium difficileis the most common nosocomial infection of the gastrointestinal tract. Most cases are associated with antibiotic therapy that alters the fecal flora, allowing overgrowth ofC difficilewith production of its toxins. Diagnosis is made by detection of the organism or toxin in the stools. A variety of different tests can be used, but none is perfect. A stool culture can be positive in someone without diarrhea, ie, a carrier. While the cytotoxin is the gold standard, it is expensive, and there is a delay before results are available. Thus, many laboratories use the enzyme-linked immunoassay tests to detect toxin ofC difficilebecause they are a more rapid screen. Depending on the specific test used, they can detect toxin A, toxin B or occasionally both. Sensitivity and specificity rates vary. First line therapy forC difficiledisease should be metronidazole 250 mg qid for 10 days. Vancomycin should be reserved for severe cases where metronidazole has failed or where metronidazole cannot be tolerated or is contraindicated. RecurrentC difficiledisease is a particularly vexing clinical problem. A variety of biotherapeutic approaches have been used. Retreatment with antibiotics is almost always necessary. In addition, the nonpathogenic yeastSaccharomyces boulardiihas been showed to be of benefit as an adjunct in preventing further recurrences.
Hepatitis in Disseminated Bacillus Calmette-Guérin Infection
Authors: Göttke Markus U , Wong Philip , Muhn Channy , Jabbari Mansour , Morin Suzanne
Published: April 2016

Local immunotherapy with an attenuated live strain ofMycobacterium bovis, bacillus Calmette-Guérin (BCG), is an effective and frequently used treatment for in situ transitional cell carcinoma (TCC) of the bladder. Success rates are high, and serious side effects are infrequent but can affect every organ system. A 79-year-old patient with recently diagnosed TCC who was treated with intravesical BCG for a recurrence after initial surgical treatment is reported. After unsuccessful attempts at bladder catheterization with the creation of a false passage for his third treatment, BCG was instilled via a suprapubic catheter the same day and again a week later. Two weeks after the third BCG instillation, the patient presented with profound lethargy and weakness to the point of not being able to get up out of a chair. He was febrile, anorexic, icteric and had hepatosplenomegaly. Disseminated BCG infection was suspected on the basis of history, clinical examination and a liver biopsy that showed noncaseating granulomatous hepatitis. Empirical treatment was started with antituberculous combination therapy. A short course of an oral corticosteroid was given. Clinical improvement was marked and sustained so that the patient could be discharged home for the full six-month course of his treatment. Disseminated BCG infection with granulomatous hepatitis can be severe and life-threatening in cases where a large intravascular inoculum of BCG may have been given inadvertently.
C1 Inhibitor Deficiency and Angioedema of the Small Intestine Masquerading as Crohn’s Disease
Authors: Burak Kelly W , May Gary R
Published: April 2016

A case of C1 inhibitor deficiency presenting as localized edema of the small intestine is described. A 16-year-old, previously healthy woman presented with recurrent attacks of abdominal pain and vomiting following minor abdominal trauma. Investigations including computed tomography scan and barium studies confirmed localized edema of the jejunum. At laparoscopy, Crohn’s disease was suspected; however, a subsequent enteroscopy was normal. Complement levels revealed a low C4 level, and C1 inhibitor deficiency was later confirmed. Attacks of abdominal pain began after starting oral contraceptives and have not returned since stopping the birth control pill. This rare cause of abdominal pain is examined, and C1 inhibitor deficiency and angioedema are reviewed.
Insulin Induces Cation Fluxes and Increases Intracellular Calcium in the HTC Rat Hepatoma Cell Line
Authors: Mathé Laurence , Vallerand Diane , Haddad Pierre S
Published: April 2016

BACKGROUND/AIMS: Rat hepatoma HTC cells were used to study conductive pathways implicated in insulin-induced cation and calcium influx into liver cells.

METHODS: Membrane potentials and currents were measured by whole-cell patch clamp. Cytosolic calcium was measured using FURA-2 fluorescence.

RESULTS: Insulin induced a gradual and reversible depolarization of 5.7±0.8 mV. Insulin-induced currents showed a linear slope conductance of 663 pS and a reversal potential of  -17.9 mV. Ion substitution experiments showed that these currents were composed mainly of a nonselective cation component. In FURA-2 experiments, insulin caused a slow monophasic rise in HTC cell calcium, which depended on the presence of extracellular calcium. Insulin also induced significant increases of 1.58- and 1.54-fold in basal calcium influx when studied by external calcium withdrawal and readmission, or by the manganese quench method, respectively. Using the latter approach, we found that 100 µM gadolinium and 10 µM SKF96365 blocked the rise of  the basal manganese quench rate induced by insulin whereas 100 µM verapamil was without effect.

CONCLUSIONS: Insulin induces inward cation currents that depolarize HTC cell membrane potentials and participate in increased calcium influx.
Comparison of IgA Endomysium Antibody and IgA Tissue Transglutaminase Antibody in Celiac Disease
Authors: Gillett Helen R , Freeman Hugh J
Published: April 2016

The antigen for immunoglobulin (Ig)Aendomysium antibody (EmA), a sensitive and specific serological marker for celiac disease, has recently been described as tissue transglutaminase (tTG). The aim of this study was to compare the assays used to measure IgAEmAand IgA tTG antibody in patients with celiac disease and disease control subjects. Sera from 21 patients with untreated celiac disease, 48 patients with treated celiac disease and 128 disease control subjects were tested both for IgA EmA with the use of indirect immunofluorescence against human umbilical cord and for IgA tTG antibody with the use of ELISA. Titres of IgA tTG antibody were significantly higher in both the untreated and treated celiac groups than in the disease control group. Titres in the treated group were, however, significantly lower than in the untreated group. A reference range was calculated to include 99.8% of the disease control group in whom small bowel biopsy showed no evidence of celiac disease. One patient from the disease control group with raised IgA tTG antibody titres and positive IgA EmA was found to have celiac disease on small bowel biopsy. The sensitivity, specificity, and positive and negative predictive values of the IgA EmA assay were all 100%. The sensitivity of the IgA tTG antibody assay was 95%, specificity 100%, positive predictive value 100% and negative predictive value 97.7%. An ELISA used to measure IgA tTG antibody is an excellent tool to screen for celiac disease and may prove useful for monitoring response to treatment.
Protective Effect of Vitamin E on Gastric Mucosal Injury in Rats with Biliary Obstruction
Authors: Cantürk Nuh Zafer , Cantürk Zeynep , Özbilim G , Yenisey C
Published: April 2016

Patients with liver disease display increased susceptibility to gastric mucosal damage. A role of free radicals has been suggested in the development of gastric mucosal damage in normal subjects. The effects of antioxidant vitamin E treatment on the liver and stomach in cirrhotic rats were examined. Fifty rats were divided into three groups. Cirrhosis was induced by bile duct ligation in 40 of 50 rats. Controls underwent a sham operation. Gastric mucosal lesions were produced by intragastric administration of 1 mL of 95% ethanol in all three groups. Twenty bile duct-ligated rats were injected intramuscularly with vitamin E (100 mg/kg/day). Liver and stomach histology, and stomach malondialdehyde and glutathione levels were determined. Portal hypertension was measured. Macroscopic and microscopic gastric mucosal injury were significantly greater in the control and common bile duct-ligated groups than in the vitamin E-pretreated group (P<0.05). The tissue malondialdehyde and glutathione levels were significantly decreased in the vitamin E-administrated group compared with the common bile duct-ligated group (P<0.001). Vitamin E administration may be cytoprotective for both the liver and gastric mucosa in bile duct-ligated rats.
Gastric Carcinoid Tumours and Pernicious Anemia: Case Report and Review of the Literature
Authors: Hagarty Sarah , Hüttner Istvan , Shibata Henry , Katz Saul
Published: April 2016

Patients with pernicious anemia are at risk of developing carcinoid tumours of the stomach. A patient with pernicious anemia and multifocal carcinoid tumours of the gastric fundus that regressed after antrectomy is presented. The frequent occurrence of gastric carcinoid tumours in patients with long-standing pernicious anemia suggests that surveillance gastroscopy and biopsies of the fundus might be indicated. Compete functional antrectomy may effectively cause these tumours to regress by removing their excessive gastrin hormonal stimulation. However, incomplete antrectomy can result in persistently elevated serum gastrin and failure of total disappearance of the carcinoid tumours.
Graft-Versus-Host Disease after Liver Transplantation Complicated by Systemic Aspergillosis with Pancarditis
Authors: Romagnuolo Joseph , Jewell Laurence D , Kneteman Norman M , Bain Vince G
Published: April 2016

Acute graft-versus-host disease (GVHD) is a common complication after bone marrow transplantation, with characteristic rash and diarrhea being the most common features. After liver transplantation, however, this phenomenon is very rare. Most transplant patients are on a variety of medications, including immunosuppressants; therefore, the differential diagnosis of skin rash or diarrhea is broad. A 37-year-old man who underwent liver transplantation for primary biliary cirrhosis, and developed a rash and watery diarrhea, is presented. Skin and colonic biopsies confirmed acute GVHD. A pulse of intravenous steroids was given. The skin rash improved, but he developed pancytopenia. His course was complicated by central line infection, jugular and subclavian vein thrombosis, pseudomembranous colitis, recurrent bacteremia, cholestasis on total parenteral nutrition and cytomegalovirus infection. After the onset of pleuritic chest pain and clinical sepsis, spiral computed tomography scan of his chest and abdomen revealed septic infarcts in multiple organs. Despite empirical treatment with amphotericin B, he died of multiorgan dysfunction syndrome within 72 h. Autopsy revealed systemic aspergillosis with pancarditis, endocardial vegetations, and septic pulmonary, splenic, hepatic and renal infarcts. The pathogenesis and experience with this rare, but often fatal, complication of liver transplantation are reviewed. In contrast to GVHD after bone marrow transplantation, pancytopenia is common and liver dysfunction is rare. One should have a high level of suspicion in the liver transplant recipient presenting with rash and/or diarrhea.
Lessons to be Learned for Gastroenterology from Recent Issues in Clinical Trial Methodology
Authors: Ohmann C , Albrecht J
Published: April 2016

Randomized trials are the preferred tool for patient-oriented research, and their main role is to enable the transfer of results from basic research to routine application. While the need for randomized trials is evident, conducting these trials is becoming increasingly difficult and complex. This article reviews actual and conflicting issues of clinical trials with respect to gastroenterology. Major problems in trial design are neglect of previous research, inadequate sample size calculations and irrelevant outcome criteria. Significant trial management problems include subversion of random allocation, and the design of systems and procedures that are inefficient, ineffective and inflexible. One of the major challenges in conducting randomized, controlled trials is obtaining informed consent because of the differing perspectives and languages of physicians and patients. Recommendations include practical guidance in obtaining informed consent, feedback of trial results to patients and support of research related to obtaining informed consent. Despite statistical guidance, several critical issues persist with respect to trial analysis. The use of confidence intervals is under-represented, the presentation of baseline data is often omitted and postsubgroup analysis is performed. Another controversial but relevant issue is the intention-to-treat analysis. Despite the formulation of standards, there is consistently poor quality of trial reporting, poor registration of unpublished trials and limited registration of ongoing trials. The authors conclude that there is a need for more randomized trials in gastroenterology. While the complexity of trial conduction has increased, so have the means of methodological and practical support. Thus, all problems can be professionally tackled, resulting in good clinical research.
Mechanisms of Alcoholic Liver Injury
Authors: French Samuel W
Published: April 2016

There have been numerous recent advances in the understanding of the mechanisms of alcoholic liver disease pathogenesis. Endotoxin-induced Kupffer cell activation plays a role in cytokine-mediated inflammatory changes in the liver, and this can be blocked by a diet high in saturated fat, by a diet containing lactobacillus, which does not produce endotoxin, by neomycin antibiotic sterilization of the gut, by eliminating Kupffer cells, or by removing tumour necrosis factor-alpha with antibody or by using tumour necrosis factor-alpha knockout mice. The fatty liver component is mainly the result of the nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide redox shift to the reduced state by ethanol oxidation generation of reduced nicotinamide adenine dinucleotide, although this too can be blocked by a diet high in saturated fat. Hepatocytic enlargement occurs due to ethanol-induced inhibition of the ubiquitin-proteasome pathway of cytoplasmic protein degradation and the retention of oxidized proteins in hepatocytes. The liver is scarred by stellate cells that have been activated by inflammatory cytokines and growth factors produced by activated Kupffer cells, and by bile ductule metaplasia. Mallory bodies and balloon cell degeneration develop through the ethanol-induced oxidative stress-protein kinase activation pathway, inhibition of phosphatase activity and inhibition of the ubiquitin-proteasome pathway.
Hereditary Angioneurotic Edema and Familial Crohn’s Disease
Authors: Freeman Hugh J
Published: April 2016

A 29-year-old man with Crohn’s disease involving the ileum and cecum was seen. He had angioneurotic edema with C-1’ esterase inhibitor deficiency. Later, his 50-year-old mother was evaluated because of abdominal pain. She had recurrent urticaria, C-1’ esterase inhibitor deficiency and radiographic studies showed Crohn’s disease of the ileum. A maternal family history revealed other members affected with either Crohn’s disease or angioneurotic edema. The clinical observations in this family suggest that angioneurotic edema associated with C-1’ esterase inhibitor deficiency may be closely linked genetically with a familial form of Crohn’s disease.
Prevalence of Celiac Disease in Collagenous and Lymphocytic Colitis
Authors: Gillett Helen Rachel , Freeman Hugh James
Published: April 2016

Both collagenous and lymphocytic colitis have been described in patients with celiac disease, suggesting an association between the conditions. Over the past few years, the availability, sensitivity and specificity of serological markers for celiac disease have improved ‐ the most recent advancement being the description of tissue transglutaminase as the major antigen for endomysium antibody. A quantitative ELISA was used to measure titres of immunoglobulin A (IgA) antibody to tissue transglutaminase (tTG) along with an immunofluorescent technique for IgA endomysium antibody (EmA) in 15 patients with lymphocytic colitis and eight with collagenous colitis to determine whether celiac disease latency could be detected. One patient with lymphocytic colitis demonstrated both elevated titres of tTG antibody and positive EmA, and small bowel biopsy confirmed celiac disease. One patient with collagenous colitis had a slightly elevated titre of tTG antibody with a negative EmA, and results of a small bowel biopsy were normal. Three other patients with lymphocytic colitis were already treated for previously diagnosed celiac disease. The prevalence of celiac disease occurring in lymphocytic colitis was found to be 27%, but no cases of celiac disease in association with collagenous colitis were found.
Outcomes Following Liver Transplantation for Patients with Alcohol- Versus Nonalcohol-Induced Liver Disease
Authors: Abosh Dory , Rosser Barry , Kaita Kelly , Bazylewski Rose , Minuk Gerald
Published: April 2016

OBJECTIVE: To document and compare the outcomes of adult patients who received liver transplants for alcohol- and nonalcohol-induced liver diseases who attended a liver transplantation follow-up clinic in an urban, nontransplantation centre at a time when no formal alcohol abuse program for transplant candidates and/or recipients was offered.

PATIENTS AND METHODS: The study population comprised 10 alcoholic patients and 48 nonalcoholic patients followed for an average of 41 months (range five to 79 months) and 46 months (range two to 116 months), respectively. Primary outcome variables included rates of recidivism, duration of abstinence after transplantation and compliance with post-transplant medical follow-up visits. Time to discharge after transplantation, episodes of graft rejection, liver and renal biochemical abnormalities, diabetes, hypertension, sepsis, strictures, complications unrelated to transplantation and changes in psychosocial status were secondary outcome variables.

RESULTS: Significant differences were found with respect to a higher incidence of recidivism (50% for alcoholic patients compared with 2% for nonalcoholic patients, P<0.0001), a shorter period of abstinence after transplantation (14.7±17.2 months for alcoholic patients compared with 26.3±23.0 months for nonalcoholic patients, P<0.05) and more missed office visits (2.7±3.5 for alcoholic patients compared with 1.0±1.9 for nonalcoholic patients, P=0.05) in the alcoholic group. The alcoholic group also had a lower incidence of rejection episodes (10% for alcoholic patients compared with 44% for nonalcoholic patients, P<0.05) but higher rates of post-transplantation diabetes (40% for alcoholic patients compared with 2% for nonalcoholic patients, P<0.05), more nontransplantation-related complications (20% for alcoholic patients compared with 0% for nonalcoholic patients, P<0.05), and higher serum creatinine but lower bilirubin and cyclosporine A levels (P<0.05, respectively). Marital separations were also more common in the alcoholic group (20% for alcoholic patients compared with 0% for nonalcoholic patients, P<0.05).

CONCLUSIONS: In the absence of formal alcohol abuse programs, the post-transplantation outcome in alcoholic patients generally does not compare well with that of patients who undergo transplantation for nonalcohol-related liver diseases.
Omeprazole Once or Twice Daily with Clarithromycin and Metronidazole forHelicobacter pyloriEradicaiton in a Canadian Community Practice
Authors: Chiba Naoki , Marshall Cheryl P
Published: April 2016

BACKGROUND: Triple therapy for one week with omeprazole, clarithromycin and metronidazole (OCM) is accepted worldwide as a first line therapy forHelicobacter pylorieradication. It is unclear whether omeprazole needs to be given once or twice daily.

OBJECTIVES: To assess the efficacy and safety of these regimens in a single-centre, Canadian practice.

METHODS: Histologically provenH pylori-positive patients were treated for seven days with clarithromycin 250 mg bid and metronidazole 500 mg bid, and randomly allocated to omeprazole 20 mg either once or twice daily in this open, cohort study. Endoscopy with histology (two antrum and two body biopsies, Giemsa stain) was done four weeks or longer after the pills were completed to assessH pylorieradication.

RESULTS: Whether omeprazole was given once or twice daily, eradication was high and the same in both arms. All-patients-treated eradication was 85% (39 of 46 in the omeprazole once daily group and 41 of 48 in the omeprazole twice daily group) and intent-to-treat eradication was 80% (39 of 49 in the omeprazole once daily group and 41 of 51 in the omeprazole twice daily group). Side effects were frequently seen, suffered by 65% to 69% of patients treated. However, these were mild and compliance was high, with 94% of patients taking all of their pills. Mild side effects included loose stools, taste disturbance, nausea, headache and upper or lower gastrointestinal gas. Only one patient (1%) from the omeprazole once daily arm stopped taking metronidazole due to excessive perspiring.

CONCLUSIONS: In this community practice, OCM triple therapy was effective whether omeprazole was given once or twice daily. For those with financial constraint, omeprazole 20 mg once daily can be considered. The regimens were well tolerated without serious adverse events.
Effect of Acid-Suppressive Therapy onHelicobactor pyloriProduction of Interleukin-8 in Gastric Mucosa
Authors: Yoshinaga Masahiro , Ohtani Akira , Tsuruta Satoru , Kato Tetsuya , Higashi Eishi , Yamada Yukio , Harada Naohiko , Nawata Hajime
Published: April 2016

BACKGROUND: Recent studies have shown that acid-suppressive therapy increases the severity ofHelicobacter pylori- associated gastritis in the corpus.

PURPOSE: To evaluate interleukin (IL)-8 production in the gastric corpus mucosa before and during acid-suppressive therapy inH pylori-infected patients.

PATIENTS AND METHODS: Ten patients with reflux esophagitis (fiveH pylori-positive and fiveH pylori-negative) were treated with omeprazole 20 mg. Serum gastrin concentrations,H pyloricolonization density and mucosal IL-8 levels in the corpus were investigated at entry and two weeks after starting therapy. IL-8 levels were measured by ELISA. The organism density was determined, and scored according to area occupied by the bacterial colonies. The presence ofH pyloriwas assessed by rapid urease testing and histological finding of gastric biopsy specimens.

RESULTS: InH pylori-positive patients, concentrations of IL-8 during therapy significantly exceeded those before therapy (36.2±6.8 versus 18.3±3.8 pg/mg protein; P<0.05) without alteringH pyloridensity. InH pylori-negative patients, IL-8 levels were similar before and during therapy (6.1±2.7 versus 6.3±3.0 pg/mg protein). Concentrations of gastrin during therapy were significantly higher than those before therapy in all patients.

CONCLUSIONS: The results suggest that acid suppression increases mucosal IL-8 levels inH pylori-infected patients with reflux esophagitis.
Prevalence Rates and an Evaluation of Reported Risk Factors for Osteonecrosis (Avascular Necrosis) in Crohn’s Disease
Authors: Freeman Hugh J , Freeman Katy J
Published: April 2016

Avascular necrosis (osteonecrosis) occurs in Crohn’s disease, but the rate of this particular complication is not known. Over 20 years, 877 patients with Crohn’s disease, 492 women (56.1%) and 385 men (43.9%), were evaluated with patient follow-up data available for a mean of 7.8 years. In this group, four men were seen with osteonecrosis. No woman was affected. All patients had typical radiological, magnetic resonance imaging or pathological changes of osteonecrosis involving the femoral heads, while two also had superimposed avascular necrosis involving the humeral heads. Patient ages ranged from 19 to 36 years at the time of diagnosis of their Crohn’s disease, and all were white. In one patient, disease was confined to the colon, while three patients had disease involving the terminal ileum and colon. Disease behaviour in two patients was classified as penetrating because of concomitant ischiorectal abscesses, while one patient developed a metastatic colon carcinoma. Ankylosing spondylitis was present in two patients, but no other extraintestinal manifestations developed. Two patients received corticosteroids as well as parenteral nutrition during the course of their disease. Two patients did not receive corticosteroids or parenteral nutrition. Of 877 patients with Crohn’s disease, 484 (55.1%) received corticosteroids during the course of the disease, 196 (22.4%) received at least one course of parenteral nutrition, and 125 (14.3%) received both corticosteroids and parenteral nutrition. A total of 311 patients (35.5%) had at least one small intestinal resection. The overall rate of avascular necrosis in Crohn’s disease was less than 0.5% but for men with Crohn’s disease was about 1%. In this series, risk of osteonecrosis could not be attributed to corticosteroid use, parenteral nutrition or both forms of therapy administered together. Small intestinal resection with loss of small intestinal absorptive area was not a risk factor for the development of osteonecrosis. Avascular necrosis (or osteonecrosis) is a very rare extraintestinal osseous complication that may occur in Crohn’s disease, independent of previously reported risk factors, including corticosteroids or parenteral nutrition with lipid emulsions.
Association between Serum Interleukin-17A Level and High-Altitude Deacclimatization Syndrome
Authors: He Binfeng , Li Hongli , Hu Mingdong , Dong Weijie , Wei Zhenghua , Li Jin , Yao Wei , Guo Xiaolan
Published: April 2016

High-altitude deacclimatization syndrome (HADAS) is emerging as a severe public health issue that threatens the quality of life of individuals who return to lower altitude from high altitude. In this study, we measured serum levels of SOD, MDA, IL-17A, IL-10, TNF-α, and HADAS score in HADAS subjects at baseline and 50th and 100th days and to evaluate the relationship between interleukins, including IL-17A, and HADAS. Our data showed that and the serum IL-17A levels and HADAS score decreased over time in the HADAS group, and serum IL-17A levels were significantly higher in the HADAS group at baseline and 50th day compared with controls (p<0.05). Furthermore, baseline serum levels of MDA and TNF-αwere significantly higher, while SOD and IL-10 levels were lower in HADAS subjects compared with controls (p<0.05). It is interesting that serum levels of IL-17A were clearly interrelated with HADAS incidence and severity (p<0.05). ROC curve analysis showed that combined serum IL-17A and IL-10 levels were a better predictor of HADAS incidence than serum levels of IL-17A or IL-10 alone. These data suggest that serum levels of IL-17A are a novel predictive index of HADAS.
Suppression of Parathyroid Hormone in a Patient with Severe Magnesium Depletion
Authors: Mutnuri Sangeeta , Fernandez Isaac , Kochar Tina
Published: April 2016

Hypomagnesemia is often associated with coexisting electrolyte abnormalities like hypokalemia and hypocalcemia. Hypocalcemia has been shown to be secondary to hypoparathyroidism induced by hypomagnesemia. Here, we discuss a case of a patient with severe hypomagnesemia and associated hypocalcemia. A 38-year-old lady was admitted to the hospital for weakness of lower extremities and an eventual fall. The exam was significant for decreased motor strength and some paresthesias. The laboratory data was significant for hypomagnesemia, hypokalemia, and low parathyroid level in the face of hypocalcemia. After replacing magnesium, the parathyroid hormone levels normalized and led to eventual correction of calcium levels without any additional calcium replacement therapy. There was complete symptom resolution with correction of electrolyte abnormalities. This case highlights the importance of looking for all associated abnormalities in a patient with hypomagnesemia and starting the replacement therapy by first replacing the magnesium and then the others as needed. Replacing the magnesium alone may correct the hypoparathyroidism and eliminate the need for calcium replacement.
The Reliability of Pharyngeal High Resolution Manometry with Impedance for Derivation of Measures of Swallowing Function in Healthy Volunteers
Authors: Omari Taher I. , Savilampi Johanna , Kokkinn Karmen , Schar Mistyka , Lamvik Kristin , Doeltgen Sebastian , Cock Charles
Published: April 2016

Purpose. We evaluated the intra- and interrater agreement and test-retest reliability of analyst derivation of swallow function variables based on repeated high resolution manometry with impedance measurements.Methods. Five subjects swallowed10×10 mL saline on two occasions one week apart producing a database of 100 swallows. Swallows were repeat-analysed by six observers using software. Swallow variables were indicative of contractility, intrabolus pressure, and flow timing.Results. The average intraclass correlation coefficients (ICC) for intra- and interrater comparisons of all variable means showedsubstantialtoexcellentagreement (intrarater ICC 0.85–1.00; mean interrater ICC 0.77–1.00). Test-retest results were less reliable. ICC for test-retest comparisons ranged fromslighttoexcellentdepending on the class of variable. Contractility variables differed most in terms of test-retest reliability. Amongst contractility variables, UES basal pressure showedexcellenttest-retest agreement (mean ICC 0.94), measures of UES postrelaxation contractile pressure showedmoderatetosubstantialtest-retest agreement (mean Interrater ICC 0.47–0.67), and test-retest agreement of pharyngeal contractile pressure ranged fromslighttosubstantial(mean Interrater ICC 0.15–0.61).Conclusions. Test-retest reliability of HRIM measures depends on the class of variable. Measures of bolus distension pressure and flow timing appear to be more test-retest reliable than measures of contractility.
Solutions for Impulsive Fractional Differential Equations via Variational Methods
Authors: Li Peiluan , Wang Hui , Li Zheqing
Published: April 2016

We investigate the boundary value problems of impulsive fractional order differential equations. First, we obtain the existence of at least one solution by the minimization result of Mawhin and Willem. Then by the variational methods and a very recent critical points theorem of Bonanno and Marano, the existence results of at least triple solutions are established. At last, two examples are offered to demonstrate the application of our main results.
Efficiency Analysis of Direct Video-Assisted Thoracoscopic Surgery in Elderly Patients with Blunt Traumatic Hemothorax without an Initial Thoracostomy
Authors: Huang Wen-Yen , Lu I-Yin , Yang Chyan , Chou Yi-Pin , Lin Hsing-Lin
Published: April 2016

Hemothorax is common in elderly patients following blunt chest trauma. Traditionally, tube thoracostomy is the first choice for managing this complication. The goal of this study was to determine the benefits of this approach in elderly patients with and without an initial tube thoracostomy. Seventy-eight patients aged >65 years with blunt chest trauma and stable vital signs were included. All of them had more than 300 mL of hemothorax, indicating that a tube thoracostomy was necessary. The basic demographic data and clinical outcomes of patients with hemothorax who underwent direct video-assisted thoracoscopic surgery without a tube thoracostomy were compared with those who received an initial tube thoracostomy. Patients who did not receive a thoracostomy had lower posttrauma infection rates (28.6% versus 56.3%,P=0.061) and a significantly shorter length of stay in the intensive care unit (3.13 versus 8.27,P=0.029) and in the hospital (15.93 versus 23.17,P=0.01) compared with those who received a thoracostomy. The clinical outcomes in the patients who received direct VATS were more favorable compared with those of the patients who did not receive direct VATS.
Dynamical Analysis of the Mechanical System with Two Degrees of Freedom Applied to the Transmission of the Wind Turbine
Authors: Scutaru Maria Luminiţa , Mitrica Bogdan
Published: April 2016

The authors develop a mathematical model to analyze the transmission of wind-driven water pumps in order to determine their dynamic response, stability, and stresses occurring in the transmission elements. The authors propose, as an innovative solution, the use of a mechanism with two degrees of freedom that provides automatically a flexibility of the transmission ratio and the harmonization of the turbine operation with the wind velocity. To verify the results a stand was carried out as physical mechanism on which measurements and recordings of the significant mechanical parameters of the system are made.
Comparative Evaluation of the BD Phoenix Yeast ID Panel and Remel RapID Yeast Plus System for Yeast Identification
Authors: Grant Michelle L. , Parajuli Shobha , Deleon-Gonsalves Raquel , Potula Raghava , Truant Allan L.
Published: April 2016

Becton Dickinson Phoenix Yeast ID Panel was compared to the Remel RapID Yeast Plus System using 150 recent clinical yeast isolates and the API 20C AUX system to resolve discrepant results. The concordance rate between the Yeast ID Panel and the RapID Yeast Plus System (without arbitration) was 93.3% with 97.3% (146/150) and 95.3% (143/150) of the isolates correctly identified by the Becton Dickinson Phoenix and the Remel RapID, respectively, with arbitration.
Genomic Analysis of a Serotype 5Streptococcus pneumoniaeOutbreak in British Columbia, Canada, 2005–2009
Authors: Miller Ruth R. , Langille Morgan G. I. , Montoya Vincent , Crisan Anamaria , Stefanovic Aleksandra , Martin Irene , Hoang Linda , Patrick David M. , Romney Marc , Tyrrell Gregory , Jones Steven J. M. , Brinkman Fiona S. L. , Tang Patrick
Published: April 2016

Background.Streptococcus pneumoniaecan cause a wide spectrum of disease, including invasive pneumococcal disease (IPD). From 2005 to 2009 an outbreak of IPD occurred in Western Canada, caused by aS. pneumoniaestrain with multilocus sequence type (MLST) 289 and serotype 5. We sought to investigate the incidence of IPD due to thisS. pneumoniaestrain and to characterize the outbreak in British Columbia using whole-genome sequencing.Methods. IPD was defined according to Public Health Agency of Canada guidelines. Two isolates representing the beginning and end of the outbreak were whole-genome sequenced. The sequences were analyzed for single nucleotide variants (SNVs) and putative genomic islands.Results. The peak of the outbreak in British Columbia was in 2006, when 57% of invasiveS. pneumoniaeisolates were serotype 5. Comparison of two whole-genome sequenced strains showed only 10 SNVs between them. A 15.5 kb genomic island was identified in outbreak strains, allowing the design of a PCR assay to track the spread of the outbreak strain.Discussion. We show that the serotype 5 MLST 289 strain contains a distinguishing genomic island, which remained genetically consistent over time. Whole-genome sequencing holds great promise for real-time characterization of outbreaks in the future and may allow responses tailored to characteristics identified in the genome.
Feature Scaling via Second-Order Cone Programming
Authors: Liang Zhizheng
Published: April 2016

Feature scaling has attracted considerable attention during the past several decades because of its important role in feature selection. In this paper, a novel algorithm for learning scaling factors of features is proposed. It first assigns a nonnegative scaling factor to each feature of data and then adopts a generalized performance measure to learn the optimal scaling factors. It is of interest to note that the proposed model can be transformed into a convex optimization problem: second-order cone programming (SOCP). Thus the scaling factors of features in our method are globally optimal in some sense. Several experiments on simulated data, UCI data sets, and the gene data set are conducted to demonstrate that the proposed method is more effective than previous methods.
Vasorelaxation Effect of Estrone Derivate EA204 in Rabbit Aorta
Authors: Li Juan , Li Wei-Qi , Yao Yao
Published: April 2016

Estrogen and its derivatives exert vascular protective effects, but the underlying mechanisms remain to be studied fully.Objective. To investigate the vasorelaxation effect and related mechanisms of an estrone derivate EA204[3-(2-piperidin-1-yl)-ethoxy-estra-1, 3, 5 (10)-trien-17-one] on isolated arterial preparation from rabbit thoracic aorta.Methods. Aortic rings from rabbit thoracic aorta were prepared and held in small organ bath filled with Krebs solution; tension change was recorded by a multichannel physiological signal collection and handling system.Results. EA204 (10−5to 10−3 M) induced a concentration-dependent relaxation of aortic rings with endothelium and without endothelium. In denuded arterial preparations, EA204 had a potent relaxing effect on isolated arterial preparations contracted with phenylephrine, norepinephrine, and high-K+solution or BaCl2. Mechanism study indicates that EA204 relaxes aortic rings by inhibiting Ca2+channels (both receptor-operating Ca2+channels and the voltage-dependent Ca2+channels were involved) to decrease extracellular Ca2+influx and intracellular Ca2+release. EA204 is different from verapamil, which is a noncompetitive inhibitor of Ca2+channels. In addition, K+channels opening may contribute to this vasorelaxation effect.Conclusion. EA204 had a potent endothelium-independent relaxing effect on isolated arterial preparation by inhibiting Ca2+channels and opening K+channels. The results suggest that EA204 is a potential compound for treatment of cardiovascular diseases in postmenopausal women.
The Small Molecule IMR-1 Inhibits the Notch Transcriptional Activation Complex to Suppress Tumorigenesis
Authors: Astudillo Luisana , Da Silva Thiago G. , Wang Zhiqiang , Han Xiaoqing , Jin Ke , VanWye Jeffrey , Zhu Xiaoxia , Weaver Kelly , Oashi Taiji , Lopes Pedro E.M. , Orton Darren , Neitzel Leif R. , Lee Ethan , Landgraf Ralf , Robbins David J. , MacKerell Alexander D. , Capobianco Anthony J.
Published: April 2016

In many cancers, aberrant Notch activity has been demonstrated to play a role in the initiation and maintenance of the neoplastic phenotype and in cancer stem cells, which may allude to its additional involvement in metastasis and resistance to therapy. Therefore, Notch is an exceedingly attractive therapeutic target in cancer, but the full range of potential targets within the pathway has been underexplored. To date, there are no small-molecule inhibitors that directly target the intracellular Notch pathway or the assembly of the transcriptional activation complex. Here, we describe an in vitro assay that quantitatively measures the assembly of the Notch transcriptional complex on DNA. Integrating this approach with computer-aided drug design, we explored potential ligand-binding sites and screened for compounds that could disrupt the assembly of the Notch transcriptional activation complex. We identified a small-molecule inhibitor, termed Inhibitor of Mastermind Recruitment-1 (IMR-1), that disrupted the recruitment of Mastermind-like 1 to the Notch transcriptional activation complex on chromatin, thereby attenuating Notch target gene transcription. Furthermore, IMR-1 inhibited the growth of Notch-dependent cell lines and significantly abrogated the growth of patient-derived tumor xenografts. Taken together, our findings suggest that a novel class of Notch inhibitors targeting the transcriptional activation complex may represent a new paradigm for Notch-based anticancer therapeutics, warranting further preclinical characterization. Cancer Res; 76(12); 3593–603. ©2016 AACR.
Myc-Driven Glycolysis Is a Therapeutic Target in Glioblastoma
Authors: Tateishi Kensuke , Iafrate A. John , Ho Quan , Curry William T. , Batchelor Tracy T. , Flaherty Keith T. , Onozato Maristela L. , Lelic Nina , Sundaram Sudhandra , Cahill Daniel P. , Chi Andrew S. , Wakimoto Hiroaki
Published: April 2016

Purpose: Deregulated Myc drives an oncogenic metabolic state, including pseudohypoxic glycolysis, adapted for the constitutive production of biomolecular precursors to feed rapid tumor cell growth. In glioblastoma, Myc facilitates renewal of the tumor-initiating cell reservoir contributing to tumor maintenance. We investigated whether targeting the Myc-driven metabolic state could be a selectively toxic therapeutic strategy for glioblastoma.

Experimental Design: The glycolytic dependency of Myc-driven glioblastoma was tested using 13C metabolic flux analysis, glucose-limiting culture assays, and glycolysis inhibitors, including inhibitors of the NAD+ salvage enzyme nicotinamide phosphoribosyl-transferase (NAMPT), in MYC and MYCN shRNA knockdown and lentivirus overexpression systems and in patient-derived glioblastoma tumorspheres with and without MYC/MYCN amplification. The in vivo efficacy of glycolyic inhibition was tested using NAMPT inhibitors in MYCN-amplified patient-derived glioblastoma orthotopic xenograft mouse models.

Results: Enforced Myc overexpression increased glucose flux and expression of glycolytic enzymes in glioblastoma cells. Myc and N-Myc knockdown and Myc overexpression systems demonstrated that Myc activity determined sensitivity and resistance to inhibition of glycolysis. Small-molecule inhibitors of glycolysis, particularly NAMPT inhibitors, were selectively toxic to MYC/MYCN–amplified patient-derived glioblastoma tumorspheres. NAMPT inhibitors were potently cytotoxic, inducing apoptosis and significantly extended the survival of mice bearing MYCN-amplified patient-derived glioblastoma orthotopic xenografts.

Conclusions: Myc activation in glioblastoma generates a dependency on glycolysis and an addiction to metabolites required for glycolysis. Glycolytic inhibition via NAMPT inhibition represents a novel metabolically targeted therapeutic strategy for MYC or MYCN-amplified glioblastoma and potentially other cancers genetically driven by Myc. Clin Cancer Res; 22(17); 4452–65. ©2016 AACR.
The Short- and Long-Term Outcome of Intratympanic Steroid Therapy as a Salvage Treatment for Acute Low-Tone Sensorineural Hearing Loss without Episodes of Vertigo
Authors: Morita Shinya , Nakamaru Yuji , Fujiwara Keishi , Iizuka Keiji , Masuya Masayori , Homma Akihiro , Fukuda Atsushi , Fukuda Satoshi
Published: April 2016

Objectives: To evaluate the hearing outcomes of intratympanic steroid (ITS) treatment for patients with acute low-tone sensorineural hearing loss (ALHL) after failure of initial therapy and to investigate the recurrence and progression to definite Ménière's disease (MD) during a long-term follow-up. Methods: We retrospectively reviewed the medical records of 90 patients with refractory ALHL who were followed up for at least 1 year between January 2000 and April 2014. Patients who responded poorly to initial medical treatment received intratympanic dexamethasone injections (ITS group) or isosorbide administration for 4 weeks (diuretic group) as salvage treatment options according to their choice of management. The control group did not receive ITS or the diuretic, due to their refusal of both medical treatments. The hearing outcomes were evaluated 1 month, 1 year and 5 years after the completion of the second-line therapy, and the rates of recurrence and progression to MD were measured during a follow-up period of at least 1 year. Results: Twenty-seven patients in the ITS group, 39 patients in the diuretic group and 24 patients in the control group were enrolled. Of these, 12 patients in the ITS group, 15 patients in the diuretic group and 12 patients in the control group were followed up for over 5 years. We found that the recovery rates and the audiometric functional values after 1 month and 1 year in the ITS group were significantly higher than those in the diuretic and control groups. However, there were no significant differences in the recovery rates or the audiometric functional values after 5 years, or in the rates of recurrence and progression to MD between the groups. Conclusions: Salvage ITS therapy can provide a relatively good short-term hearing outcome for ALHL patients who have persistent hearing loss despite conventional treatment. However, both recurrence and progression to MD after treatment were observed in some patients during the long-term follow-up.
Fatigue, Pain, Anxiety and Depression in Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Authors: Merkies Ingemar S.J. , Kieseier Bernd C.
Published: April 2016

Background: In the clinical evaluation of patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), scant attention is paid to symptoms such as fatigue, pain and anxiety/depression. We aimed at addressing seminal studies that focused on the burden of these symptoms and their impact on quality of life (QoL) in these conditions. Summary: Fatigue, pain, and anxiety/depression are increasingly being recognized in patients with GBS and CIDP, although their pathophysiological provenance remains unknown. Fatigue and pain are significant in terms of prevalence and intensity, may be a presenting symptom, and can persist for years after apparent functional recovery, suggesting residual injury. Anxiety/depression has also been examined although studies are limited. Despite their negative impact on QoL, the long-term dynamics of these symptoms in patients with GBS and particularly CIDP receiving therapy in routine clinical practice have not been systematically evaluated. Such observations formed the basis for the ongoing (GAMEDIS) studies evaluating the effect of Gamunex® on fatigue and depression in patients with CIDP, of which some preliminary data are presented. Key Messages: Strength and sensory deficits are the main areas of focus in patients with GBS and CIDP, but they do not explain the total reduction in QoL, suggesting the possible role of other complaints. A more comprehensive approach to patient care demands that factors such as pain, fatigue and anxiety/depression receive greater attention. The non-interventional GAMEDIS studies are expected to provide valuable insight into the long-term effectiveness of Gamunex® in everyday practice.