http://nova.newcastle.edu.au/vital/access/services/Feed ${session.getAttribute("locale")} 5 http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12640 Objective: To investigate the effects of weight loss and time post laparoscopic gastric banding surgery (LGB) on urinary and sexual function. Material and Methods: 653 females and 145 males who underwent LGB over the last 10 years at a single centre in Australia were contacted by post and asked to complete validated questionnaires. Results: The pre-surgery body-mass index (BMI) was higher in males than females (47.3 vs 43.5); 65% of the females and 24% of males previously had some degree of urinary incontinence (UI). There were significant weight and BMI losses in males and females (23.2 kg and 7.51 vs 22.7 kg and 8.28; P < 0.0001). In females there were significant improvements in the ICIQ-SF (P= 0.0008) and Quality of Life (P < 0.0001) scores. For each kilogram lost there was a 0.05 improvement in the ICIQ score (P= 0.03) in females. There were also postoperative improvements in all symptoms of UI and stress incontinence in females but urge incontinence worsened, when adjusted for weight loss. In males there was no improvement in UI with weight loss after LGB. There was no relationship with time and UI in either gender; 83.3% of males reported a degree of ED before LGB. There was improvement in the IIEF score in males post LGB but there was worsening of erectile index (P= 0.005) and orgasmic function (P= 0.002) when adjusted for time. More males had started using phosphodiesterase type 5 inhibitors, post-LGB. Conclusions: Surgically induced weight loss by LGB improved overall UI, quality of life and stress incontinence in females but urge incontinence worsened. There was no improvement in UI with weight-loss or overall sexual function after LGB in males. However, erectile index and orgasmic function worsened when adjusted for time. Further evaluation is required by means of larger prospective studies involving urodynamic testing. 2013-03-14T03:39:42.425Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12513 Purpose: Transcutaneous electrical stimulation (TES) speeds up colonic transit in children with slow-transit constipation (STC). This study examined if concurrent upper gastrointestinal dysmotility (UGD) affected response to TES. Methods: Radio-nuclear transit studies (NTS) were performed before and after TES treatment of STC as part of a larger randomised controlled trial. UGD was defined as delayed gastric emptying and/or slow small bowel transit. Improvement was defined as increase of ≥1 Geometric Centre (median radiotracer position at each time [small bowel = 1, toilet = 6]). Results: Forty-six subjects completed the trial, 34 had NTS after stimulation (21 M, 8–17 years, mean 11.3 years; symptoms >9 years). Active stimulation increased transit in >50% versus only 25% with sham (p = 0.04). Seventeen children also had UGD. In children with STC and either normal upper GI motility (NUGM) and UGD, NTS improved slightly after 1 month (57 vs. 60%; p = 0.9) and more after 2 months (88 vs. 40%; p = 0.07). However, mean transit rate significantly increased with NUGM, but not UGD (5.0 ± 0.2: 3.6 ± 0.6, p < 0.01). Conclusion: Transcutaneous electrical stimulation was beneficial for STC, with response weakly associated with UGD. As measured by NTS, STC children with NUGM responded slightly more, but with significantly greater increased transit compared to those with UGD. Higher numbers are needed to determine if the difference is important. 2013-02-01T01:20:04.182Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10450 The esophagus and stomach have specific motor functions that propel ingested material through the upper gastrointestinal tract, while the stomach also helps to grind the food into a more digestible form. The proximal, striated muscle portion of the esophagus quickly moves the bolus into the distal esophagus where smooth muscle contractions propel it through the lower esophageal sphincter into the stomach. In addition to allowing the bolus to pass, the lower esophageal sphincter is tonically contracted in its resting state, which prevents gastroesophageal reflux. The proximal stomach receptively relaxes to accommodate the swallowed bolus, while the distal stomach has functions to grind the food into smaller sizes to facilitate digestion. The antrum and pylorus have an additional function as a “sieve” to prevent emptying of particles until they have been reduced to an appropriate size. The stomach has a specific region that coordinates the motor activity of the stomach and to a degree the entire upper gastrointestinal tract (pacemaker region). This region initiates the periodic contraction profile that pushes both digested and undigested material through the gastrointestinal tract (phase III of the migrating motor complex). This complicated physiology is affected by both hormones and extrinsic innervation, but the pacemaker resides in the specialized nervous system of the gastrointestinal tract, most likely in the interstitial Cajal cells. 2012-03-20T02:00:03.961Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7050 The dissemination of malignant gastric cells to the peritoneum occurs frequently, usually as an early event in disease, and results in poor patient prognosis. Surgery and chemotherapy offer limited therapeutic success. The low-pathogenic human enterovirus, Echovirus 1 (EV1), is an oncolytic virus that selectively targets and destroys malignant prostate and ovarian cancer xenografts in vivo. Lytic EV1 infection requires the cell surface expression of α2β1, an integrin involved in the dissemination of gastric cancer cells to the peritoneum. Herein, we evaluated the capacity of EV1 for anti-neoplastic cell action in gastric peritoneal carcinomatosis. Flow cytometric analysis demonstrated that α2β1 was abundantly surface expressed on a panel of gastric cancer cell lines, rendering the majority of lines highly susceptible to in vitro lytic EV1 infection and supportive of efficient viral progeny production. A bioluminescent MKN-45-Luc SCID mouse model of peritoneal dissemination was developed to allow real-time non-invasive monitoring of peritoneal tumor burden. Employing this mouse model, we demonstrated a therapeutic dose-response for escalating oncolytic EV1 doses. Taken together, these results emphasize the exciting potential for EV1 as a single or adjunct therapy for the control of the peritoneal dissemination of gastric cancer. 2012-01-30T05:02:17.758Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4311 Research Doctorate - Doctor of Philosophy (PhD) 2011-12-07T23:40:05.030Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:9539 Background and Aims: Upper gastrointestinal hemorrhage remains a problem in spite of improved diagnosis and management. There is sparse knowledge of recent epidemiology and outcomes. We wanted to evaluate the characteristics and outcomes of patients with upper gastrointestinal hemorrhage over a 4-year period in a tertiary referral hospital. Methods: We prospectively collected data on patients admitted with upper gastrointestinal hemorrhage to John Hunter Hospital between August 2004 and December 2008. Variables of interest included age, gender, co-morbidities, and time to endoscopy. Main outcomes included etiology, treatment, and survival. Variceal and non-variceal bleeds were analyzed separately. Results: There were 792 admissions from 734 unique patients (61% male) with a mean age of 66 years. The most frequent causes of non-variceal bleeds (88%) included ulcers 265 (33%); Mallory Weiss tear 91 (11%); esophagitis 60 (8%), and malignancy 29 (4%). Most patients had one or more co-morbidity (74%). Transfusion was not employed in 41%. Overall mortality was 4.0% (5.4% in the variceal and 3.9% in the non-variceal group). Only 1.9% of patients had surgery. Conclusions: Patients presenting with upper gastrointestinal hemorrhage are overall elderly with significant co-morbidities. Our overall mortality and surgery rates are lower than in previously published international data. 2011-12-05T23:20:02.147Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:9515 1. Mechanisms underlying the generation and propagation of gastrointestinal slow wave depolarizations have long been controversial. The present review aims to collate present knowledge on this subject with specific reference to slow waves in gastric smooth muscle. 2. At present, there is strong agreement that interstitial cells of Cajal (ICC) are the pacemaker cells that generate slow waves. What has been less clear is the relative role of primary types of ICC, including the network in the myenteric plexus (ICC-MY) and the intramuscular network (ICC-IM). It is concluded that both ICC-MY and ICC-IM are likely to serve a major role in slow wave generation and propagation. 3. There has been long-standing controversy as to how slow waves ‘propagate’ circumferentially and down the gastrointestinal tract. Two mechanisms have been proposed, one being action potential (AP)-like conduction and the other phase wave-based ‘propagation’ resulting from an interaction of coupled oscillators. Studies made on single bundle gastric strips indicate that both mechanisms apply with relative dominance depending on conditions; the phase wave mechanism is dominant under circumstances of rhythmically generating slow waves and the AP-like propagation is dominant when the system is perturbed. 4. The phase wave mechanism (termed Ca²⁺ phase wave) uses cyclical Ca²⁺ release as the oscillator, with coupling between oscillators mediated by several factors, including: (i) store-induced depolarization; (ii) resultant electrical current flow⁄depolarization through the pacemaker cell network; and (iii) depolarization- induced increase in excitability of downstream Ca²⁺ stores. An analogy is provided by pendulums in an array coupled together by a network of springs. These, when randomly activated, entrain to swing at the same frequency but with a relative delay along the row giving the impression of a propagating wave. 5. The AP-like mechanism (termed voltage-accelerated Ca²⁺ wave) propagates sequentially like a conducting AP. However, it is different in that it depends on regenerative store Ca²⁺ release and resultant depolarization rather than regenerative activation of voltage-dependent channels in the cell membrane. 6. The applicability of these mechanisms to describing propagation in large intact gastrointestinal tissues, where voltagedependent Ca²⁺ entry is also likely to be functional, is discussed. 2011-11-29T02:40:03.853Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:9502 This systematic review evaluates the current evidence base for eating behavior changes after laparoscopic adjustable gastric banding (LAGB). A literature search from 1990 to February 2010 was conducted to identify original studies that assessed eating behavior in adults who have undergone LAGB. Sixteen articles (14 separate studies) met inclusion criteria. Although strength of the evidence base was limited by observational study designs and methodological weaknesses, results suggest that positive changes in eating behavior occur after surgery, including reduced over-eating in response to emotional and situational cues. There is some evidence to suggest that uncontrolled eating behaviors persist in some individuals, and that this may be problematic for weight loss after surgery. Few studies examined the relationship between changes in eating behavior and weight loss; thus, optimal behavioral strategies for promoting positive weight outcomes remain unclear. Further interventional research addressing the inherent limitations of the current-evidence base is required to guide development of evidence-based management guidelines for LAGB in future. 2011-11-29T00:00:17.212Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7349 We studied potential interactions between the endoplasmic reticulum (ER) stress response and the MEK/ERK pathway. Induction of ER stress did not trigger significant apoptosis, but caused rapid activation of ERK1/2 in gastric cancer cells. Inhibition of MEK enhanced ER stress-induced apoptosis via a caspase-dependent, mitochondria-mediated mechanism. This was associated with blockage of ER stress-mediated up-regulation of GRP78. The latter appeared to be critical in antagonizing the apoptosis-inducing potential of ER stress. Thus, activation of MEK/ERK by ER stress is necessary for induction of GRP78 that protects against apoptosis in gastric cancer cells submitted to ER stress. 2011-03-10T21:40:16.962Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7237 Herbicides are commonly ingested for self-harm, but relatively little has been published on poisoning with herbicides other than paraquat and glyphosate. We report here a case series of patients with acute exposure to a combination herbicide (brand name Tiller Gold or Whip Super) containing the selective phenoxy herbicide compounds fenoxaprop-P-ethyl and ethoxysulfuron and a safener isoxadifen ethyl. Clinical data on all patients presenting with Tiller Gold or Whip Super poisoning to two General Hospitals in Sri Lanka from 2002–2008 were collected prospectively until discharge. Eighty-six patients with a history of Tiller Gold or Whip Super ingestion were included. The main clinical features were an epigastric burning sensation and vomiting; however, most of those who vomited had received gastric lavage or forced emesis. Eight patients had a reduced level of consciousness on admission (Glasgow coma scale 9–14) that resolved without intervention over several hours. Only symptomatic and supportive care was required. The median hospital stay was 1 day (IQR: 1–2) and the case fatality was zero (95% confidence interval: 0–4.2%). This low case fatality compared favorably with the case fatality of other common herbicides in our cohort: paraquat >40%, propanil >10%, 4-chloro-2-methylphenoxyacetic acid > 5%, and glyphosate >2%. This combination herbicide product appears to be safe in patients with acute self-poisoning, particularly in comparison with other herbicides, and causing few clinical features. 2011-02-21T04:00:09.724Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1902 This study aimed to assess the transit tolerance of potential probiotic dairy propionibacteria strains in human upper gastrointestinal tract in vitro, and to evaluate the effect of food addition on viability of these strains in simulated pH 2.0 gastric juices. The transit tolerance of 13 dairy propionibacteria strains was determined at 37 °C by exposing washed cell suspensions to simulated gastric juices at pH values at 2.0, 3.0, and 4.0, and simulated small intestinal juices (pH 8.0) with or without 0.3% bile salts. The viability of dairy propionibacteria in pH 2.0 simulated gastric juice with So-Good™ original soymilk or Up & Go® liquid breakfast was also determined. The simulated gastric transit tolerance of dairy propionibacteria was strain-dependent and pH-dependent. All tested strains were tolerant to simulated small intestinal transit. The addition of So-Good™ original soymilk or Up & Go® liquid breakfast greatly enhanced the survival of dairy propionibacteria strains in pH 2.0 simulated gastric juices. Dairy propionibacteria strains demonstrate high tolerance to simulated human upper gastrointestinal tract conditions and offer a relatively overlooked, yet alternative source for novel probiotics besides Lactobacillus and Bifidobacterium. 2010-04-27T06:58:19.695Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1262 Background and Aims:The etiology and pathophysiology of stomach carcinoma is complex, and the mechanism whereby H. pylori directly or indirectly induces carcinoma remains unclear. In this study, interleukin (IL)-8, IL-4 and interferon (IFN)-γ were measured in the tissue culture supernatant of gastric organ cultures from subjects with chronic gastritis with or without H. pylori infection, and with or without gastric cancer and gastric dysplasia. Results:Interleukin-8 levels were higher in cancer- and H. pylori-infected gastritis subjects than in H. pylori-negative subjects (12.95 ± 3.16, 10.48 ± 1.55 and 4.49 ± 1.28 ng/mL, respectively). Elevated levels of IFN-γ were detected in both H. pylori-infected and non-infected subjects with uncomplicated gastritis (72.23 ± 19.0 and 34.61 ± 5.30 pg/mL) and in non-infected dysplasia subjects (88 ± 20.5 pg/mL). Background levels of IL-4 (≤ 9.4 pg/mL) in uncomplicated gastritis subjects and relatively high levels of IL-4 in dysplasia subjects (25.8 ± 7.3 pg/mL) were detected. In contrast, trace amounts of IFN-γ (16.01 ± 0.35 pg/mL) and high levels of IL-4 (42.81 ± 8.49 pg/mL) in gastric biopsy culture supernatants were found in cancer subjects. Mucosal IL-4 levels (but not IL-8 levels) correlated with infection and mucosal anti-H. pylori immunoglobulin G antibody. Conclusions:The significant differences between gastritis with and without cancer and dysplasia indicated a shift from a Th1 to a Th2 helper cell pattern of cytokine secretion. This study has identified a local mucosal defect in gastric cancer. The near absence of IFN-γ production from the mucosa at the margins of the tumor may be a critical factor in promoting growth of neoplastic cells. 2010-04-27T06:56:10.402Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1251 Background: Epidemiological studies have demonstrated strong links between Helicobacter pylori infection and gastric adenocarcinoma. Recent studies suggest that cell-mediated immunity influences the outcome of infection, including the development of gastric adenocarcinoma. The T-cell response can be characterized in terms of the secreted cytokine profile, which in turn influences the B-cell response including the balance of IgG subclass antibody. Methods: Serum anti-H. pylori IgG, IgG1 and IgG2 antibodies were studied by ELISA in subjects with benign gastric diseases, gastric dysplasia and gastric adenocarcinoma. Results: The distribution patterns of IgG subclass anti-H. pylori antibody varies significantly between H. pylori-linked benign and malignant disease in subjects infected with H. pylori. Significantly lower IgG2 levels were found in subjects with gastric adenocarcinoma compared with those with reflux esophagitis, chronic gastritis, gastric ulcer, and peptic ulcer, while IgG1 antibody remained at similar levels in both benign and malignant disease. A limited study of seropositive subjects with premalignant change was consistent with the fall in IgG2 antibody pre-dating malignant change, although pre-eradication results are needed to validate these data. Conclusions: These studies indicate that subjects with low levels of IgG2 anti-H. pylori antibody are at risk of gastric adenocarcinoma, and that the previously described linkage between gastric adenocarcinoma and low total IgG antibody does not simply reflect reduced gastric colonization. The diagnostic value of this assay for pre-endoscopy screening is attractive. 2010-04-27T06:38:30.921Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1733 Ca²⁺ imaging and multiple microelectrode recording procedures were used to investigate a slow wave-like electrical rhythmicity in single bundle strips from the circular muscle layer of the guinea-pig gastric pylorus. The 'slow waves' (SWs) consisted of a pacemaker and regenerative component, with both potentials composed of more elementary events variously termed spontaneous transient depolarizations (STDs) or unitary potentials. STDs and SW pacemaker and regenerative potentials exhibited associated local and distributed Ca²⁺ transients, respectively. Ca²⁺ transients were often larger in cellular regions that exhibited higher basal Ca²⁺ indicator-associated fluorescence, typical of regions likely to contain intramuscular interstitial cells of Cajal (ICCIM). The emergence of rhythmicity arose through entrainment of STDs resulting in pacemaker Ca²⁺ transients and potentials, events that exhibited considerable spatial synchronicity. Application of ACh to strips exhibiting weak rhythmicity caused marked enhancement of SW synchronicity. SWs and underlying Ca²⁺ increases exhibited very high 'apparent conduction velocities' ('CVs') orders of magnitude greater than for sequentially conducting Ca²⁺ waves. Central interruption of either intercellular connectivity or inositol 1,4,5-trisphosphate receptor (IP₃R)-mediated store Ca²⁺ release in strips caused SWs at the two ends to run independently of each other, consistent with a coupled oscillator-based mechanism. Central inhibition of stores required much wider regions of blockade than inhibition of connectivity indicating that stores were voltage-coupled. Simulations, made using a conventional store array model but now including depolarization coupled to IP₃R-mediated Ca²⁺ release, predicted the experimental findings. The linkage between membrane voltage and Ca²⁺ release provides a means for stores to interact as strongly coupled oscillators, resulting in the emergence of Ca²⁺ phase waves and associated pacemaker potentials. This distributed pacemaker triggers regenerative Ca²⁺ release and resultant SWs. 2010-04-27T06:10:13.658Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5677 The Gan et al. paper on this issue adds to the growing body of evidence showing that procedures that bypass the upper small intestine have a more rapid and more profound effect on type 2 diabetes than purely restrictive procedures. The challenge for the Obesity Society of Australia and New Zealand (which represents obesity surgeons) in conjunction with Royal Australasian College of Surgeons is to continue to develop a meaningful credentialing process and a comprehensive training programme, which covers the full range of surgical options. 2010-04-27T04:49:49.075Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5563 Although cisplatin has been shown to induce both apoptosis and necrosis in cancer cells, the potential interconnections between these modes of cell death induced by the drug remain unknown. We studied this phenomenon in gastric cancer cell lines and identified one cell line (SGC-7901) that underwent apoptosis, and another cell line (BGC-823) that primarily underwent nonapoptotic cell death, in response to cisplatin. Apoptosis in cisplatin-treated SGC-7901 cells seemed to be caspase dependent and was mediated, at least in part, by the BH3-only protein, Noxa. This was evidenced by the rapid upregulation of Noxa and inhibition of apoptosis by small interfering RNA knockdown of Noxa. Nonapoptotic cell death induced by cisplatin in BGC-823 cells was characterized by lack of DNA fragmentation, delayed externalization of phosphatidylserine, caspase independence, plasma membrane disruption, and intracellular vacuole formation, indicative of necrosis. Surprisingly, blockage of apoptosis induction by a general caspase inhibitor or by Noxa small interfering RNA in SGC-7901 failed to protect against cisplatin-induced cell death. Under such conditions, SGC-7901 cells displayed cellular features associated with necrosis. Cisplatin-induced apoptosis, thus, seems to precede necrosis when the apoptotic machinery is operative. When the apoptosis program is defective, necrotic cell death takes place as an alternative pathway leading to cell demise. Induction of different modes of cell death that are interrelated in the same cells by cisplatin has the potential to be exploited in formulating new adjuvant cancer therapies. 2010-04-27T04:45:49.581Z ]]>