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Biomedical subjects

James Toouli

Publications and source records attributed to James Toouli.

17 recordsLinked to original sources
PubMed2006

Functional gallbladder and sphincter of oddi disorders.

The functional disorder of the gallbladder (GB) is a motility disorder caused initially either by metabolic abnormalities or by a primary motility alteration. The functional disorders of the sphincter of Oddi (SO) encompass motor abnormalities of either the biliary or the pancreatic SO. Dysfunction of the GB and/or biliary SO produce similar patterns of pain. The pain caused by a dysfunction of the pancreatic SO can be similar to that of acute pancreatitis. The symptom-based diagnostic criteria of motility dysfunction of the GB and biliary SO are episodes of moderate to severe steady pain located in the epigastrium and right upper abdominal quadrant that last at least 30 minutes. GB motility disorder is suspected after gallstones and other structural abnormalities have been excluded. This diagnosis should then be confirmed by a decreased GB ejection fraction induced by cholecystokinin at cholescintigraphy and after disappearance of the recurrent biliary pain after cholecystectomy. Symptoms of biliary SO dysfunction may be accompanied by features of transient biliary obstruction, and those of pancreatic SO dysfunction are associated with elevation of pancreatic enzymes and even pancreatitis. Biliary-type SO dysfunction is more frequently recognized in postcholecystectomy patients. SO manometry is valuable to select patients with sphincter dysfunction; however, because of the high incidence of complications, these patients should be referred to an expert unit for such assessment. Thus invasive tests should be performed only in the presence of compelling clinical evidence and after noninvasive testing has yielded negative findings. The committee recommends that division of the biliary or pancreatic sphincters only be considered when the patient has severe symptoms, meets the required criteria, and other diagnoses are excluded.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed2005

Biliary scintigraphy versus sphincter of Oddi manometry in patients with post-cholecystectomy pain: is it time to disregard the scan?

Sphincter of Oddi (SO) dysfunction is diagnosed using manometry, and patients with an abnormal SO basal pressure respond well to division of the SO. However, manometry is invasive and is associated with a low, yet significant, incidence of complications. Scintigraphy techniques have been developed with the aim of providing a noninvasive means of assessing SO motility. However, when compared with SO manometry these techniques fall short in sensitivity and specificity for diagnosing SO dysfunction. Furthermore, they do not select patients who will respond to treatment. Consequently, the quest for development of a noninvasive investigation for diagnosis of SO dysfunction continues. In the mean time, improved manometric techniques that enhance reproducibility and reduce complications have been developed.

Biliary Tract↗
PubMed2005

Highly selective inhibition of inducible nitric oxide synthase ameliorates experimental acute pancreatitis.

OBJECTIVES: Inducible nitric oxide synthase (iNOS) activity is increased in experimental acute pancreatitis. The aim of this study was to evaluate treatment with the selective iNOS inhibitors AR-C (AR-C102222AA) and L-NIL (L-N6-(1-iminoethyl)-lysine) in experimental acute pancreatitis. METHODS: Acute pancreatitis was induced in anesthetized Australian possums by topical administration of carbachol on the sphincter of Oddi. AR-C treatment was 2 intravenous infusions (2.5 micromol/kg over 15 minutes) at 2 and 4 hours after acute pancreatitis induction. L-NIL treatment was an intraarterial infusion (1 mg/kg/h) from 2 hours after acute pancreatitis induction. At 8 hours, pancreatic tissue was harvested and inflammation assessed (histologic score). Blood samples were collected for plasma amylase, lipase, and amino acid levels. Blood pressure, central venous pressure, supplementary fluids, and urine output were monitored. RESULTS: Treatment with AR-C or L-NIL reduced the plasma levels of amylase and the volume of supplementary fluids and improved the histological score (all P < 0.05). In animals with acute pancreatitis, plasma arginine levels were reduced (P < 0.05), while citrulline and ornithine levels increased (P < 0.05), consistent with increased nitric oxide production. Treatment with AR-C ameliorated the reduced arginine level. CONCLUSIONS: Treatment with AR-C or L-NIL, commencing 2 hours after the induction of acute pancreatitis, has significant and beneficial effects in experimental acute pancreatitis in Australian possums.

Acute Disease↗
PubMed2004

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 microl 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.

Animals↗
PubMed2004

Surgical management of obesity using a soft adjustable gastric band.

BACKGROUND: Laparoscopically inserted adjustable gastric bands are an effective means of weight reduction for obese patients. METHODS: The Swedish Adjustable Gastric Band was evaluated prospectively in a consecutive series of 273 patients from August 1996 to March 2003. RESULTS: The first 58 patients had their band sited by the 'peri-gastric' technique, with the subsequent 215 using the 'pars flaccida' technique, which provides better posterior fixation of the band. Results from these two groups were considered separately. Prolapse of the stomach through the band was the major complication occurring in 13 of the 58 peri-gastric patients (22.4%). Median preoperative body mass index (BMI) was 42.1, falling below 30 by 2 years. In the pars flaccida group there were no instances of prolapse, but the major complication was three cases of band erosion (1.4%). Median preoperative BMI was 42.9 for this group, falling to 32 by 3 years. There was one death in the series due to myocardial infarction. CONCLUSIONS: Results compare favourably with other published adjustable gastric band series. Weight loss with the SAGB appears durable overall with an acceptable complication rate once an appropriate technique is employed. Consistent life-long follow up is necessary to achieve the best result.

Adult↗
PubMed2004

Second-generation recombinant hemoglobin molecules do not stimulate sphincter of Oddi, gallbladder or duodenal motility in the Australian brush-tailed possum.

BACKGROUND: Several studies have investigated the effects of hemoglobin-based oxygen carriers on gastrointestinal motility. Diaspirin cross-linked hemoglobin reduces sphincter of Oddi trans-sphincteric flow and increases duodenal motility in the Australian brush-tailed possum, effects attributed to nitric oxide (NO) scavenging. Recently, second-generation recombinant hemoglobin molecules with reduced NO scavenging ability have been developed. AIM: To determine the effects of two second-generation recombinant hemoglobin solutions and the prototype recombinant hemoglobin with high NO binding, on duodenal and biliary motility in the Australian brush-tailed possum. METHOD: Blood pressure; duodenal, sphincter of Oddi and gallbladder motility; and trans-sphincteric flow were recorded. The effects of recombinant hemoglobin or human serum albumin (control) solutions on these parameters were investigated. Each solution was infused intravenously at 1 mL/kg/min to deliver 250 mg/kg or 500 mg/kg. RESULTS: Duodenal contraction frequency was stimulated by the high dose of prototype recombinant hemoglobin, but not by a comparable dose of second-generation recombinant hemoglobin. The induced duodenal activity occurred in the later phase of the experimental period. In contrast, biliary motility and trans-sphincteric flow were not altered by any hemoglobin solution. The high dose of all the hemoglobin solutions elevated blood pressure, whereas the low dose solutions did not alter any parameter measured. CONCLUSION: At the doses studied, the second-generation recombinant hemoglobin with reduced NO binding capacity did not significantly alter duodenal and biliary motility, supporting the need for further studies to evaluate their potential usefulness as blood substitutes.

Animals↗
PubMed2003

Effects of bioactive agents on biliary motor function.

Our understanding of biliary motility under normal and pathophysiologic conditions is still incomplete, but there have been recent advances. Of particular interest are the mechanisms involved in gallbladder filling and emptying, with a focus on understanding the processes underlying impaired gallbladder emptying leading to gallbladder dyskinesia and the formation of gallstones or cholecystitis. The sphincter of Oddi (SO) is a complex neuromuscular structure. Recent studies have attempted to unravel the specific neural or hormonal mechanisms operating under normal physiologic conditions and those that may lead to SO dysfunction. Furthermore, new research fronts are emerging, including the role of leptin in obese patients with impaired biliary motility and the action of electroacupuncture for possible treatment of SO dysfunction. This review illustrates the broad front of current research regarding the effects of bioactive agents on biliary motility, including enteric hormones, nitric oxide, opioids, inflammatory mediators, leptin, protease inhibitors, neurotransmitters, and electroacupuncture.

Animals↗
PubMed2003

Training surgeon scientists.

Beginning in 1995, College research resources were orientated towards the support and training of surgeon scientists. A questionnaire was sent to recipients of College awards in order to gauge a measure of outcome of this policy. Although it is early days, a significantly high number of awardees have either completed or are completing research degrees. There has been a successful allocation of National Health and Medical Research Council funding to the College surgeon scientists and a large number are already in academic positions. A significant number of publications have resulted from the College-funded research. At this early stage, the programme for creating surgeon scientists appears to be on track.

General Surgery↗
PubMed2003

Changes in gallbladder motility and gallstone formation following laparoscopic gastric banding for morbid obestity.

UNLABELLED: Morbid obesity is associated with cholesterol gallstone formation, a risk compounded by rapid weight loss. Laparoscopic gastric banding allows for a measured rate of weight loss, but the subsequent risk for developing gallstones is unknown. METHOD: Twenty-six normal-weight volunteers (body mass index [BMI] less than 30) were compared with 14 morbidly obese patients (BMI greater than 40). Gallbladder volumes were measured ultrasonographically, after fasting and following stimulation with intravenous cholecystokinin-octapeptide (CCK-8) RESULTS: Preoperatively, fasting gallbladder volume and residual volume after CCK stimulation were both two times greater in the obese group (P<0.02 versus controls). Per cent gallbladder emptying was not different. Gallbladder refilling was four times higher in the obese patients (P<0.01). By six weeks postoperatively, the obese patients lost 1.4+/-0.1% body weight per week. Gallbladder emptying decreased 18.4% (80.3+/-3.9% to 65.5+/-6.9%; P<0.05); residual volume rose one-third (not significant), and refilling fell 60.5% (0.43+/-0.09 to 0.26+/-0.04 mL/min; P=0.07). Three patients with weight losses of greater than 1.7% per week developed gallstones; gallbladder emptying fell outside the 95 percentile. By six months, weight loss slowed to 0.5+/-0.1% per week; gallbladder motility improved modestly. No further stones developed. CONCLUSION: Rapid weight loss following laparoscopic gastric banding impairs gallbladder emptying and when pronounced, gallstones form by six weeks postoperatively. The accompanying reduction in gallbladder emptying, increased gallbladder residual volume and decreased refilling promote gallbladder stasis and hence stone formation.

Adult↗
PubMed2002

Characterization of circular muscle motor neurons of the duodenum and distal colon in the Australian brush-tailed possum.

The motor innervation of the duodenum and distal colon remains uncharacterized within the same species. Our aim was to compare the projections and neurochemical properties of duodenal and distal colon circular muscle motor neurons. Circular muscle motor neurons were retrogradely traced by using a neural tracer in vitro, processed for choline acetyltransferase (ChAT) and nitric oxide synthase (NOS) immunoreactivity and then visualized by using indirect immunofluorescence. A mean of 372 +/- 64 and 156 +/- 23 neurons (mean +/- SEM) were tracer-labeled within the duodenum and colon, respectively. The ChAT+/NOS- neurons comprised 57.6 +/- 6.6% and 39.6 +/- 4.4% of all labeled cells in the duodenum and colon, respectively, and projected mainly in the oral direction. Of all labeled cells, the ChAT-/NOS+ neurons comprised 8.5 +/- 2.3% in the duodenum and 46.6 +/- 5.0% in the distal colon and projected mainly in the anal direction. Of the remainder, 20.6 +/- 5.0% and 8.2 +/- 2.4% were ChAT+/NOS+ and 13.2 +/- 0.9% and 5.6 +/- 1.4% were ChAT-/NOS- in the duodenum and distal colon, respectively. Within both regions, the distribution of the ChAT+/NOS- and ChAT-/NOS+ neurons are consistent with the ascending excitatory and descending inhibitory reflexes. The proportion of ChAT-/NOS+ neurons is greater within the colon in comparison with the duodenum. A considerable proportion of duodenal motor neurons were ChAT+/NOS+ and ChAT-/NOS-. These two classes may underlie nonperistaltic motor patterns, which predominate within the duodenum. These findings demonstrate regional differences in the innervation of intestinal circular muscle.

Acetylcholine↗
PubMed2002

Sphincter of Oddi dysfunction: is there a role for medical therapy?

If the mechanism of pain in patients with sphincter of Oddi (SO) dysfunction is functional obstruction of the biliary tract, and at least in some patients it results from sphincter smooth muscle hypertrophy, then smooth muscle relaxants should have a theoretic role in the management of these patients. Calcium channel antagonists and other smooth muscle relaxants have been shown in "acute" manometric studies to alter SO motility. However, the effect of these agents on vascular smooth muscle remains a concern and often limits their use. At present the role of medical therapy is somewhat unclear because few well-conducted studies have used manometric criteria for the diagnosis of SO dysfunction and the selection of patients for therapy. The main drawback is that no drugs appear to be specific for the SO, long acting, and free of side effects.

Animals↗
PubMed2002

Biliary Dyskinesia.

Biliary dyskinesia is a motility disorder that affects the gallbladder and sphincter of Oddi. The motility disorder of the gallbladder is called gallbladder dyskinesia. Patients with this condition present with biliary-type pain, and investigations show no evidence of gallstones in the gallbladder. The diagnosis is made by performing a gallbladder ejection fraction, which is a radionuclide investigation. An abnormal gallbladder ejection fraction has a value less than 40%. Patients with an abnormal gallbladder ejection fraction should undergo cholecystectomy. This procedure has been shown to be effective in curing the symptoms in over 90% of patients. Motility disorder of the sphincter of Oddi is called sphincter of Oddi dysfunction. This disorder is categorized as two distinct types--biliary sphincter of Oddi dysfunction and pancreatic sphincter of Oddi dysfunction. Typically, patients with biliary sphincter of Oddi dysfunction present with biliary-type pain on average 4 to 5 years after having undergone cholecystectomy. Sphincter of Oddi manometry is essential in making a diagnosis of abnormal motility of the sphincter. On manometry, diagnosis of a sphincter of Oddi stenosis should lead to division of the sphincter. Sphincterotomy results in long-term relief of symptoms in more than 80% of patients. Pancreatic sphincter of Oddi dysfunction clinically presents with recurrent episodes of pancreatitis of unknown cause. Having ruled out all of the common causes of pancreatitis, sphincter of Oddi manometry of the pancreatic duct sphincter should be performed. When manometric stenosis is diagnosed, these patients should undergo division of both the biliary and pancreatic duct sphincter. This treatment results in relief of symptoms in more than 80% of patients.

Journal Article↗
PubMed2002

Endothelin-3 induces both human and opossum gallbladder contraction mediated mainly by endothelin-B receptor subtype in vitro.

BACKGROUND: Endothelins are produced by gallbladder epithelial cells, suggesting a role in the regulation of gallbladder function. AIMS: To characterize the effect of endothelin-3 (ET-3) on human and Australian possum gallbladder contractility and identify the receptor(s) involved. METHODS: Human and possum gallbladder muscle strips were exposed to cumulative concentrations of ET-3 (10 pmol/L-100 nmol/L). Strips were pretreated with either tetrodotoxin (TTX) (1 micro mol/L), the selective ET receptor antagonists BQ-123 (ET(A)), BQ-788 (ET(B)), alone or together, or the mixed ET antagonist tezosentan (all 1 micro mol/L). Maximal changes in tone were measured and expressed as percentage of carbachol (100 micro mol/L)-induced tone. ANOVA was used for statistical analysis. RESULTS: Endothelin-3 induced a concentration-dependent increase in tone in both human and pos-sum strips (P < 0.05) and at 100 nmol/L represented 44.2 +/- 4.5% and 40.3 +/- 4.6% of carbachol-induced tone, respectively. The effect on human strips was TTX insensitive, whereas the possum concentration-response curve was shifted to the right. Individually, BQ-123 and BQ-788 shifted the human concentration-response curve to the right, but a greater inhibition by BQ-788 was achieved in the possum (P < 0.05). However, BQ-123 plus BQ-788 further reduced the ET-3 effect (P < 0.001) to a level comparable to that observed in the presence of tezosentan in both human and possum strips. CONCLUSION: Endothelin-3 produces potent gallbladder contraction in vitro, acting mainly via ET(B) receptors and also interacting with ET(A)receptors. The receptors are located on the smooth muscle, but in possum gallbladder, neural receptors may also be involved. These findings suggest that ET-3 may regulate motility of possum and human gallbladder.

Adult↗
PubMedDate not supplied

Endothelins induce gallbladder contraction independent of elevated blood pressure in vivo in the Australian possum.

Endothelin levels are elevated in shock, sepsis, and cholestatic jaundice, and an effect on biliary motility may be postulated. The aim of this study was to determine whether (1) endothelin-1 and endothelin-3 induce gallbladder contraction in vivo, (2) the response is caused by changes in blood pressure, and (3) the response is nerve mediated. Gallbladder pressure and blood pressure were measured in 38 anesthetized possums. Endothelin-1 or endothelin-3 (5 to 200 pmol/kg) was administered by close intra-arterial injection. Tetrodotoxin (9 microg/kg) or the mixed endothelin antagonist tezosentan was infused at a rate of 10 or 100 nmol/kg/min (close intra-arterial injection). Maximum changes in gallbladder pressure (% of carbachol-induced contraction) and blood pressure (mm Hg) were determined. Statistical analysis was carried out by means of repeated-measures analysis of variance and Kruskal-Wallis test. Both endothelin-1 and endothelin-3 induced dose-dependent increases in gallbladder pressure and blood pressure (P < 0.05), which were unaffected by pretreatment with tetrodotoxin. The endothelin-1-induced gallbladder pressure but not blood pressure was reduced by the higher dose of tezosentan (P < 0.03). The lower dose of tezosentan also produced a decrease in the endothelin-3-induced gallbladder pressure (P < 0.02) but not in blood pressure, whereas the higher dose reduced the blood pressure with no further reduction in gallbladder pressure (P < 0.05). Endothelins increase gallbladder motility in vivo, acting directly on the smooth muscle and independent of changes in blood pressure.

Anesthetics, Local↗
PubMedDate not supplied

Being CLEAR: evaluation of a module to teach critical appraisal to surgeons.

The CLEAR (critical literature evaluation and research) module was developed to meet an identified need in both trainees and Fellows for the basic tools to allow them to plan research projects and evaluate research papers. This paper describes briefly the way in which the module was developed and presents results of participant evaluation of the mature product, which indicate a high level of satisfaction.

Curriculum↗
PubMedDate not supplied

Inguinal hernia repair with the Kugel patch.

BACKGROUND: The Kugel hernia patch (Davol, Cranston, RI, USA) for treatment of inguinal hernias is a minimal access technique of inguinal herniorrhaphy, which aims to combine the utility of the open operation with the advantages of the laparoscopic procedures. The aim of the present study is to report an initial experience of a cohort of patients with inguinal hernias undergoing repair using this technique. METHODS: A prospective series of 107 inguinal hernia repairs performed between January 2000 and October 2003 in 96 patients, using the Bard Kugel hernia patch were entered into the study. Patient comfort, complications, activity levels postoperations and early recurrence were evaluated. RESULTS: The median age was 76 years (range 23-88 years). There were 107 inguinal hernias repaired. There were 11 bilateral, 39 left and 46 right sided hernias, 12 were recurrent. There were no major complications. There were no early recurrences. At 6 and 12 months there were one and two hernia recurrences, respectively. A further recurrence was noted at 2 years. There was no consistent relationship between having hernia surgery and loss of mobility. There was no difference in straight leg raising noted following surgery compared to the patients' preoperative score. Ability to shower, dress, reach the toilet or perform housework by day 7 returned to normal. Shopping activities were resumed by day 30 in all patients. CONCLUSIONS: The Kugel hernia operation is associated with minimal postoperative pain and rapid return to normal activity. There is a modest hernia recurrence rate, which needs to be addressed.

Activities of Daily Living↗