Charmaine M. Woods

The sphincter of Oddi: understanding its control and function.

Abstract  The most common functional disorders of the biliary tract and pancreas are associated with disordered motility of the sphincter of Oddi (SO). The SO is a neuromuscular structure located at the junction of the bile and pancreatic ducts with the duodenum. The primary functions of the SO are to regulate the delivery of bile and pancreatic juice into the duodenum, and to prevent the reflux of duodenal contents into the biliary and pancreatic systems. Disordered motility of the SO leads to the common and painful clinical conditions of SO dysfunction and acute pancreatitis. In order to understand normal SO motility, studies have been performed addressing SO function, control of spontaneous SO activity, responses to bioactive agents, SO innervation, and reflexes with other gastrointestinal organs. These studies have led to the current understanding of how the SO functions and may permit the development of targeted therapy for SO dysfunction and acute pancreatitis. This review summarizes the current knowledge regarding the control and regulation of SO motility, highlighting laboratory based and clinical research performed over the last 5 years.

Biomarkers and laryngopharyngeal reflux.

Laryngopharyngeal reflux is a controversial but increasingly made diagnosis used in patients with a collection of often non-specific laryngeal symptoms. It is a clinical diagnosis, and its pathophysiology is currently poorly understood. Previous reflux research has focused on injurious agents, acid, pepsin and biomarker expression. Failure of intrinsic defences in the larynx may cause changes in laryngeal epithelia, particularly alterations in carbonic anhydrases and E-cadherin. Carbonic anhydrase III levels vary in the larynx in response to laryngopharyngeal reflux, depending on location. Expression of E-cadherin, a known tumour suppressor, is reduced in the presence of reflux. Mucin expression also varies according to the severity of reflux. Further research is required to define the clinical entity of laryngopharyngeal reflux, and to identify a definitive mechanism for mucosal injury. Understanding this mechanism should allow the development of a comprehensive model, which would enable future diagnostic and therapeutic interventions to be developed.

A double-blind randomized controlled trial of normal saline, lactated Ringer's, and hypertonic saline nasal irrigation solution after endoscopic sinus surgery.

Background Nasal douching is commonly performed after endoscopic sinus surgery (ESS). There is a lack of studies comparing the clinical effect of various douching solutions after ESS. This study investigated the clinical effects of normal saline, lactated Ringers, and hypertonic saline nasal douching solutions after ESS. Methods Adult patients (41.8 ± 12.9 years) undergoing bilateral ESS for chronic rhinosinusitis at a single tertiary referral center e blindly randomized to one of the three study solutions and reviewed on postoperative weeks 1, 3, and 6. The 20-item Sino-Nasal Outcome Test (SNOT-20) scores, visual analog scale (VAS) symptom scores, digital video capture of the sinus cavities, and mucociliary clearance (MCC) times were performed at each visit. The mucosa appearances were scored by a second investigator, blinded to the douching solution. Results Seventy-four patients were recruited. All groups showed an improvement with treatment in SNOT-20 scores and VAS scores, as well as endoscopic evaluation of mucosa appearance over time. There was no improvement of MCC during the treatment period. Irrigation with lactated Ringers solution resulted in better symptom scores in SNOT-20 (p < 0.05) and VAS (p < 0.05), compared with irrigation with normal saline or hypertonic saline solutions. Patients receiving hypertonic saline solutions had less polypoidal mucosa at week 6. Conclusion Douching with lactated Ringers solution after ESS results in better improvement in sinonasal symptoms, compared with normal saline or hypertonic saline solutions.

The tripeptide analog feG ameliorates severity of acute pancreatitis in a caerulein mouse model

Acute pancreatitis (AP) is associated with significant morbidity and mortality; however, there is no specific treatment for this disease. A novel salivary tripeptide analog, feG, reduces inflammation in several different animal models of inflammation. The aims of this study were to determine whether feG reduced the severity of AP and modifies the expression of pancreatic ICAM-1 mRNA during AP in a mouse model. AP was induced in mice by hourly (x12) intraperitoneal injections of caerulein. A single dose of feG (100 microg/kg) was coadministered with caerulein either at time 0 h (prophylactic) or 3 h after AP induction (therapeutic). Plasma amylase and pancreatic MPO activities and pancreatic ICAM-1 mRNA expression (by RT-PCR) were measured. Pancreatic sections were histologically assessed for abnormal acinar cells and interstitial space. AP induction produced a sevenfold increase in plasma amylase, a tenfold increase in pancreatic MPO activity, and a threefold increase in interstitial space, and 90% of the acinar cells were abnormal. Prophylactic treatment with feG reduced the AP-induced plasma amylase activity by 45%, pancreatic MPO by 80%, the proportion of abnormal acinar cells by 30%, and interstitial space by 40%. Therapeutic treatment with feG significantly reduced the AP-induced abnormal acinar cells by 10% and the interstitial space by 20%. Pancreatic ICAM-1 mRNA expression was upregulated in AP and was reduced by 50% with prophylactic and therapeutic treatment with feG. We conclude that feG ameliorates experimental AP acting at least in part by modulating ICAM-1 expression in the pancreas.

Modified uvulopalatopharyngoplasty and coblation channeling of the tongue for obstructive sleep apnea: a multi-centre Australian trial

STUDY OBJECTIVES To investigate the surgical outcomes and efficacy of modified uvulopalatopharyngoplasty (mod UPPP) and Coblation channelling of the tongue (CCT) as a treatment for obstructive sleep apnea (OSA). METHODS Adult patients with simple snoring or obstructive sleep apnea were treated with combined modified UPPP, bilateral tonsillectomy, and CCT (N = 48). Full polysomnography was performed preoperatively and 3 months postoperatively. Postoperative clinical assessment, sleep questionnaires, and patient demographics including body mass index were compared to preoperative data. All polysomnograms were re-scored to AASM recommended criteria by 2 sleep professionals. RESULTS The preoperative AHI (median and interquartile range) of 23.1 (10.4 to 36.6) was lowered to a postoperative AHI of 5.6 (1.9 to 10.4) (p < 0.05). The Epworth Sleepiness Scale score fell from 10.5 (5.5 to 13.5) to 5.0 (3.09 to 9.5) (p < 0.05). Morbidity of the surgery was low, with no long-term complications recorded. CONCLUSIONS Modified UPPP combined with CCT is a highly efficacious intervention for OSA with minimal morbidity. It should be considered for individuals who fail or are intolerant of CPAP or other medical devices.

The possum sphincter of Oddi pumps or resists flow depending on common bile duct pressure: a multilumen manometry study.

The sphincter of Oddi (SO) regulates trans‐sphincteric flow (TSF) by acting primarily as a pump or as a resistor in specific species. We used the Australian possum SO, which functions similarly to the human SO, to characterize SO motility responses to different common bile duct (CBD) and duodenal pressures. Possum CBD, SO and attached duodenum (n= 18) was mounted in an organ bath. External reservoirs were used to impose CBD (0–17 mmHg) and duodenal (0, 4, 7 mmHg) pressure. Spontaneous SO activity was recorded using four‐lumen pico‐manometry and TSF was measured gravimetrically. Temporal analysis of manometric and TSF recordings identified three functionally distinct biliary‐SO regions, the proximal‐SO (juxta‐CBD), body‐SO and papilla‐SO. At CBD pressures < 3 mmHg the motor activity of these regions was coordinated to pump fluid. Proximal‐SO contractions isolated fluid within the body‐SO. Peristaltic contraction through the body‐SO pumped this fluid through the papilla‐SO (17–27 μl contraction), which opened to facilitate flow. CBD pressure > 3.5 mmHg resulted in progressive changes in TSF to predominantly passive ‘resistor’‐type flow, occurring during proximal‐SO–body‐SO quiescence, when CBD pressure exceeded the pressure at the papilla‐SO. Progression from pump to resistor function commenced when CBD pressure was 2–4 mmHg greater than duodenal pressure. These results imply that TSF is dependent on the CBD–duodenal pressure difference. The papilla‐SO is pivotal to TSF, relaxing during proximal‐SO–body‐SO pumping and closing during proximal‐SO–body‐SO quiescence. The pump function promotes TSF at low CBD pressure and prevents bile stasis. At higher CBD pressure, the papilla‐SO permits TSF along a pressure gradient, thereby maintaining a low pressure within the biliary tract.

Submucosal lingualplasty for adult obstructive sleep apnea

Objective To measure quality-of-life outcomes, polysomnographic outcomes, and adverse effects for a new technique of tongue reduction in obstructive sleep apnea. Study Design Case series. Setting Tertiary hospital. Subjects and Methods Consecutively treated adult patients (N = 27) with obstructive sleep apnea having submucosal lingualplasty in 2007 were studied. All had concurrent or previous uvulopalatoplasty ± palatal advancement. Full polysomnography preoperatively and 3.7 ± 0.4 months postoperatively, scored using the American Academy of Sleep Medicine 2007 criteria, was recorded. Snoring severity score, Epworth Sleepiness Scale, and complication data were collected at a 2.61 ± 0.08-year follow-up via questionnaire. Results Mean snoring severity score fell from 7.1 ± 0.4 to 2.3 ± 0.6 (P < .05). Epworth Sleepiness Scale score fell from 8.3 ± 1.1 to 5.8 ± 1.0 (P < .05). The apnea-hypopnea index (AHI) fell from 44.0 ± 4.3 to 12.5 ± 2.3 (P < .05). Success, defined as achieving an AHI <15 postoperatively, was observed in 74% (20/27), with each of these patients achieving a reduction in AHI >50%. Lowest oxygen saturation improved from 84 ± 1 to 88 ± 1 (P < .05). Pain was mild to moderate. Short-term postoperative complications included bleeding (3.7%) and infection (14.8%). Some minor long-term (6 months) alteration in tongue function was reported with regard to speech (47%), swallow (33%), and taste (33%). Conclusion Submucosal lingualplasty with concurrent palatal surgery is a promising treatment option in adult patients with obstructive sleep apnea with macroglossia.

Galanin mediates the pathogenesis of cerulein-induced acute pancreatitis in the mouse.

Objectives: Acute pancreatitis (AP) is characterized by pancreatic microcirculatory and secretory disturbances. As galanin can modulate pancreatic vascular perfusion, we sought to determine if galanin plays a role in AP. Methods: Acute pancreatitis was induced in wild-type and galanin gene knockout mice by intraperitoneal injections of cerulein. The severity of AP was evaluated (plasma amylase and lipase, myeloperoxidase activity, and acinar cell necrosis) with and without treatment with galanin or the antagonist galantide. Galanin receptor messenger RNA expression in mouse pancreas was measured by reverse transcription-polymerase chain reaction and Western blot analysis. Results: Galantide ameliorated AP, reducing all indices by 25% to 40%, whereas galanin was without effect. In galanin knockout mice, all indices of AP were reduced 25% to 50% compared with wild-type littermates. Galanin administration to the knockout mice exacerbated AP such that it was comparable with the AP induced in the wild-type mice. Conversely, administration of galantide to the galanin knockout mice did not affect the AP, whereas AP was ameliorated in the wild-type mice. The 3 galanin receptor subtypes are expressed in mouse pancreas, with receptor subtype 3 expression predominating. Conclusions: These data implicate a role for galanin in AP and suggest a potential clinical application for galanin antagonists in treatment.

Human lysozyme has fungicidal activity against nasal fungi

Background The cationic antimicrobial peptide lysozyme is the most prevalent innate immune protein in nasal secretions but there is a paucity of research regarding its role in paranasal sinus disease. Lysozyme is generally regarded as an antibacterial agent; however, some data suggest activity toward yeast. This study was designed to determine if lysozyme displays fungicidal activity toward fungi commonly identified in patients with chronic rhinosinusitis (CRS) or fungal sinusitis. Methods Using a colony-forming unit assay the fungicidal activity of lysozyme (0, 0.5, 5, and 50 micromolar; 0- to 7-hour treatment) was tested against strains of Aspergillus fumigatus, the yeast Candida albicans, and other fungi commonly identified in mucin of patients with CRS. Fungi cultured directly from the mucin of two CRS patients were also tested to determine if they were resistant to the fungicidal activity of lysozyme. Results The fungicidal effect of lysozyme was both concentration and time dependent. After 7-hour treatment lysozyme (5 micromolar) had >80% fungicidal activity against A. fumigatus, Penicillium sp., Acremonium sp., C. albicans, and Candida parapsilosis. The fungicidal activity of lysozyme toward Alternaria alternata could not be determined. Lysozyme was also fungicidal toward the clinical isolates A. fumigatus and Aspergillus terreus cultured from the mucin of CRS patients. Conclusion Lysozyme displays fungicidal activity toward many fungi commonly identified in patients with CRS, as well as clinical fungi isolates cultured from the mucin of CRS patients. Additional studies are required to determine the regulation of lysozyme in CRS.

A novel preparation to study rat pancreatic spinal and vagal mechanosensitive afferents in vitro

Abstract  The management of pancreatic pain is a significant clinical problem so understanding of how sensory signals are generated in pancreatic tissue is fundamental. We aimed to characterize mechanosensitive and chemosensitive properties of pancreatic spinal and vagal afferents in vitro. Spinal and vagal afferent preparations from Sprague–Dawley rats were established incorporating the left splanchnic nerve or vagus nerves respectively. The common bile duct was cannulated for distension of the pancreatic duct with fluid. Nerve discharge evoked by blunt probing, duct distension or electrical stimulation was obtained from teased nerve bundles using standard extra‐cellular recording. Discharge from 197 spinal afferent bundles was recorded, of which 57% displayed spontaneous activity. Blunt probing revealed 61 mechanosensitive receptive fields which were associated primarily with arteries/blood vessels (33/61) and the parenchyma (22/61). All mechanosensitive responses were slowly adapting, with 33% continuing to discharge after termination of the stimulus and 60% displaying a response threshold <10 g. Application of chemical mediators (bradykinin, histamine, 5‐hydroxytryptamine, cholecystokinin octapeptide) evoked a response from 31/57 units, with 33% excitatory and 23% inhibitory. Spontaneous discharge was recorded from 72% of 135 vagal bundles. Mechanosensitive receptive fields were not identified in the pancreas but were evident in adjacent organs. No spinal or vagal afferent response to duct distension was obtained. In conclusion, pancreatic mechanosensitive spinal afferents are common, in contrast to pancreatic mechanosensitive vagal afferents indicating that pancreatic sensory innervation is predominantly spinal. Chemosensitive spinal afferent nerve endings are present in the pancreas and respond to a variety of inflammatory and physiological mediators.