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Biomedical subjects

R T Padbury

Publications and source records attributed to R T Padbury.

At least 19 recordsLinked to original sources

Liver transplantation for HCV-associated liver cirrhosis: predictors of outcomes in a population with significant genotype 3 and 4 distribution.

End-stage liver disease associated with hepatitis C virus (HCV) infection is now the leading indication for liver transplantation in adults. However, reinfection of the graft is universal. We aimed to determine predictors of outcome of HCV-liver transplant recipients in the Australian and New Zealand communities. The following variables were analysed: demographic factors, coexistent pathology at the time of transplantation, HCV genotype, and donor age. Outcomes measures were: 1. mortality; 2. development of HCV-related complications, which were stage 3 or 4 fibrosis, or mortality from HCV-related graft failure, or both. Between January 1989 and December 30, 1999, 182 patients were transplanted for HCV-associated cirrhosis. The median follow-up period was 4 years (range, 0 to 13 years). Genotype data were available on 157 patients. The distribution of genotypes among the 157 patients was as follows: 36 (23%) genotype 1a, 30 (19%) genotype 1b, 4 (9%) genotype 1, 17 (11%) genotype 2, 41 (26%) genotype 3a, and 16 (10%) genotype 4. Eight (5%) patients were HCV-polymerase chain reaction (PCR)-negative (but HCV-antibody-positive). Donor age and genotype 4 were associated with an increased risk of retransplantation or death (P <.001 and.05, respectively). Meanwhile, donor age, genotype 4, and pretransplant excess alcohol were risk factors for the development of HCV-related complications (P =.004,.008, and.02, respectively). In contrast, patients with genotype 3a were less likely to develop HCV-related complications (P =.05). In a population of HCV liver transplant recipients with a heterogeneous genotype distribution, donor age, and genotype 4, were predictors of a worse outcome, whereas genotype 3 was associated with a more favorable outcome.

Adult↗

Sphincter of Oddi dysfunction associated with choledochal cyst.

The pathophysiology of choledochal cysts remains unclear, although an association with anomalous pancreato-biliary junction and the reflux of pancreatic enzymes into the biliary tree is known. Sphincter of Oddi (SO) manometry was performed in three patients with choledochal cysts. All patients exhibited an elevated basal pressure diagnostic of sphincter of Oddi dysfunction. Two patients exhibited anomalous pancreato-biliary junction. This report suggests an association between the choledochal cyst and sphincter of Oddi dysfunction, and may suggest that SO dysfunction plays a role in choledochal cyst formation.

Adult↗

A modification of isolated Roux loop reconstruction after pancreaticoduodenectomy.

BACKGROUND: Different techniques of reconstruction following pancreaticoduodenectomy have been described. A new modification using an isolated Roux-en-Y loop is reported. METHODS: The isolated loop is taken up to bile duct rather than pancreas as previously described. RESULTS: Seventeen patients have undergone this procedure. Two pancreatic fistulae developed, both following postoperative abscess formation. There was no operative mortality. CONCLUSION: This reconstruction provides separation of biliary and pancreatic fluid but adds two further benefits: the wide jejunal lumen allows for an easier pancreaticojejunal anastomosis, particularly when operating on a soft pancreas, and separation of gastric and biliary anastomoses prevents the efflux of bile into stomach.

Aged↗

A prospective randomized trial of day-stay only versus overnight-stay laparoscopic cholecystectomy.

BACKGROUND: Although the feasibility of laparoscopic cholecystectomy performed as day surgery has been established, cost and recovery time have not previously been evaluated in a prospective comparative fashion. METHODS: Patients were randomized to day stay only or overnight stay, and a nurse assessed the former postoperatively at home. All patients were reviewed weekly or as required if problems occurred. Costing comparisons were made between the two groups using Trendstar software. RESULTS: A total of 131 patients were evaluated after randomization (60 day-stay only patients and 71 overnight-stay patients). A total of 18.3% of the day-stay patients required in-hospital admission for nausea, vomiting, or pain, or after conversion to open operation; 18.3% of the overnight group required an extended length of stay for similar reasons. After discharge, two day-stay and three overnight-stay patients required readmission, only one had a significant complication. The mean times to return to normal activity averaged 1.8 weeks (SE: 0.1 weeks) and 1.9 weeks (SE: 0.1 weeks) for day-stay and overnight-stay groups, respectively (P = 0.63), and costs of $2732 (SE: $76) compared to $2835 (SE $110), respectively (P = 0.94). CONCLUSIONS: In the present randomized controlled study, day-stay management did not compromise postoperative patient outcome. In the setting of a major teaching hospital there was no cost advantage when compared to overnight-stay management.

Ambulatory Surgical Procedures↗

Somatostatin stimulates the brush-tailed possum sphincter of Oddi in vitro and in vivo.

BACKGROUND & AIMS: Somatostatin, a neuropeptide and hormone, is found in the biliary tract of several species. The aim of this study was to map the distribution of somatostatin-like immunoreactive nerve fibers in the extrahepatic biliary tract of the Australian possum and to determine the pharmacological effects of somatostatin 1-14 on sphincter of Oddi activity in vitro and in vivo. METHODS: Tissue was harvested for immunohistochemistry and sphincter of Oddi for circular or longitudinal muscle contractility. In anesthetized possums, sphincter of Oddi motility was measured by manometry, and transsphincteric flow was measured gravimetrically. RESULTS: Somatostatin immunoreactivity was evident in gallbladder ganglia nerve cell bodies and in nerve fibers of the common bile duct and sphincter of Oddi. Somatostatin 1-14 increased circular and longitudinal muscle contraction amplitude 3-4-fold (P < 0.05), but only the longitudinal muscle contraction amplitude was tetrodotoxin sensitive. Somatostatin 1-14 stimulated spontaneous sphincter of Oddi motility in a tetrodotoxin-insensitive manner, increasing basal pressure, contraction frequency, and amplitude 2-4-fold (P < 0.05) and reducing transsphincteric flow to 25% of control (P < 0.0001). CONCLUSIONS: Somatostatin-like immunoreactivity is present in the extrahepatic biliary tree, and somatostatin 1-14 stimulates sphincter of Oddi smooth muscle and nerves. The major action is direct stimulation of sphincter of Oddi circular muscle, which reduces transsphincteric flow.

Animals↗

Gastrin-releasing peptide stimulates gallbladder motility but not sphincter of Oddi motility in Australian brush-tailed possum.

The neural distribution and action of gastrin-releasing peptide in the extrahepatic biliary tree of the Australian brush-tailed possum was investigated. Immunohistochemical staining of fixed specimens demonstrated gastrin-releasing peptide-containing nerves throughout the neural plexuses of the gallbladder, sphincter of Oddi, and mucosa of the common bile duct. Gastrin-releasing peptide (5-2000 ng/kg) increased gallbladder tone to a level equivalent to that produced by cholecystokinin octapeptide (160 ng/kg). This action was tetrodotoxin-insensitive. Sphincter of Oddi motility and transsphincteric flow were not altered. Possible mediation of the gallbladder response by gastrin was examined. Gastrin (50-2500 ng/kg) stimulated gastric acid secretion, elevated gallbladder motility to 64% of that produced by gastrin-releasing peptide, and did not alter sphincter of Oddi motility. In conclusion, gastrin-releasing peptide-containing nerves are found in the neural plexus of the possum extrahepatic biliary tree. Gastrin-releasing peptide induces gallbladder contraction in part by a direct action on gallbladder smooth muscle and also via release of gastrin.

Animals↗

Substance P stimulates sphincter of Oddi motility and inhibits trans-sphincteric flow in the Australian brush-tailed possum.

Substance P containing nerves are widely distributed throughout the gastrointestinal tract. The aims of this study were to determine the distribution of substance P containing nerves in the extrahepatic biliary tree of the Australian brush-tailed possum and to characterize the effect of exogenous substance P on the sphincter of Oddi (SO) motility and transphincteric flow in vivo. Immunohistochemical staining of fixed specimens (n = 8) found moderate numbers of substance P containing nerve cell bodies and fibres throughout the neural plexuses of the SO, in particular in the serosal and intraluminal nerve trunks of the SO and gallbladder. Synthetic porcine substance P (1-2000 ng kg-1), administered by close intra-arterial injection (i.a.; n = 7), produced a dose-dependent elevation in basal pressure [P < 0.01] and an associated dose-dependent reduction in trans-sphincteric flow [P < 0.0001]. Substance P had no significant dose-dependent effect on SO phasic contraction amplitude or frequency. Tetrodotoxin (9 micrograms kg-1, i.a.) did not inhibit the effect of substance P on SO motility and trans-sphincteric flow (n = 5). In conclusion, substance P containing nerves are found throughout the possum extrahepatic biliary tree. Exogenous substance P stimulates SO motility and reduces trans-sphincteric flow in vivo by acting directly on the sphincter smooth muscle.

Animals↗

Treatment of a giant haemangioma of the liver with Kasabach-Merritt syndrome by orthotopic liver transplant a case report.

We describe a case of giant cavernous haemangioma of the liver with disseminated intravascular coagulopathy (Kasabach-Merritt syndrome) which was cured by orthotopic liver transplant. A 47 year old man presented with bleeding and tender massive hepatomegaly after tooth extraction. Investigations showed disseminated intravascular coagulopathy and a giant hepatic haemangioma involving both lobes of the liver. Initial treatment failed to resolve the coagulopathy and liver resection was attempted. At laparotomy the tumour was unresectable and the only option for cure was to offer a liver transplantation. The orthotopic liver transplant was performed 20 days after initial laparotomy. Subsequently, all coagulation parameters returned to normal and the patient remains well after 12 months. Orthotopic liver transplant can be considered for giant hepatic haemangioma with Kasabach-Merritt syndrome when resection is necessary and a partial hepatectomy is not technically feasible.

Disseminated Intravascular Coagulation↗

Galanin modulates sphincter of Oddi function in the Australian brush-tailed possum.

The neuropeptide galantin (GAL) is found in neurons in the biliary tract of several species. We mapped the distribution of GAL-like immunoreactive nerve (GAL-LI) fibers in the sphincter of Oddi of the Australian brush-tailed possum by immunohistochemistry. The pharmacological effects of GAL in vitro and in vivo were studied by measuring sphincter of Oddi muscle strip contractility and transsphincteric flow, respectively. Muscle layers, and ganglionated and perivascular plexuses, contained GAL-LI nerve fibers. Exogenous GAL caused a concentration-dependent (10(9)-10(-6)M) increase in the spontaneous longitudinal but not circular muscle contractions. At 10(-6) M GAL, contractile activity was elevated two- to fourfold. This response was tetrodotoxin insensitive but competitively inhibited by galantide (10(-8)-10(-7) M). In vivo, intra-arterial bolus injections of GAL (1001000 ng/kg), decreased transsphincteric flow, with a maximum reduction to 80.2 +/- 6.8% of control. In conclusion, GAL appears to selectively stimulate longitudinally oriented sphincter of Oddi smooth muscle via a direct mechanism, which results in a modest reduction in transsphincteric flow.

Animals↗

Laparoscopic surgery in women with a clinical diagnosis of acute appendicitis.

OBJECTIVES: To assess the routine use of diagnostic laparoscopy and laparoscopic appendicectomy in women with a clinical diagnosis of acute appendicitis. METHODS: Women who presented with a clinical diagnosis of acute appendicitis between 1 January 1992 and 31 August 1993 were prospectively assessed and 107 underwent diagnostic laparoscopy. RESULTS: Appendicitis was confirmed in 63 women (59%) and no diagnosis could be made in seven (6%). An alternative diagnosis, most commonly a gynaecological disorder, was made in 37 women (35%). Twenty-eight women with an alternative diagnosis (76%) did not require a laparotomy. Seventy-three patients had a laparoscopic appendicectomy, with an 8% conversion rate to an open operation. The morbidity rate for laparoscopic procedures was 3%, the median inpatient stay was two days and the median time to return to normal activities was eight days. CONCLUSIONS: Diagnostic laparoscopy should be performed in women who present with a clinical diagnosis of acute appendicitis to confirm the diagnosis, reduce the rate of unnecessary appendicectomy and avoid an unnecessary laparotomy. When acute appendicitis is confirmed, appendicectomy may be performed laparoscopically.

Activities of Daily Living↗

Gastric devascularization and splenectomy for bleeding gastric varices.

Gastric varices may be associated with oesophageal varices in patients with portal hypertension. Control of haemorrhage from gastric varices is often difficult. Between June 1988 and February 1990, six patients underwent gastric devascularization in an effort to control life-threatening haemorrhage from bleeding gastric varices after non-operative measures failed. In all six patients the bleeding was controlled. There was one peri-operative death due to hepatic failure. Four patients experienced postoperative respiratory or urinary tract infections that responded to appropriate antibiotic and respiratory support measures. After a mean follow-up period of 44 months, eradication of gastric varices was achieved in all five survivors. Gastric devascularization is an effective surgical measure for good palliation and control of life-threatening haemorrhage from bleeding gastric varices.

Adult↗

Extended preservation of the liver with UW solution--is it justifiable?

The outcome of 228 liver grafts in 208 elective adult recipients was assessed to identify any adverse effects of extending the length of cold preservation with UW solution beyond 12 hr. A total of 114 grafts had been preserved < 12 hr--median 9.5 (group I) and 114 > 12 hr--median 14.5 (group II). Intraoperative blood and blood product usage, graft function, hospital stay, and graft and patient survival were identical in the two groups. Biliary strictures occurred in 5.7% of grafts (8 anastomotic (3 group I, 5 group II; 5 hilar/nonanastomotic: 3 group I, 2 group II). There was no graft or patient loss due to the hilar strictures but 1 patient died following reconstruction of an anastomotic stricture (0.4%). It is concluded that extending the cold preservation to approximately 15 hr does not adversely affect outcome after liver transplantation.

Adenosine↗

Endoscopic retrograde cholangiopancreatography following laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is the preferred method of treatment for symptomatic choledocholithiasis. Since its introduction there has been an increase in postoperative diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to assess the indications and results of ERCP following laparoscopic cholecystectomy. Sixty-one patients had an ERCP following laparoscopic cholecystectomy. Two broad groups were identified: Group 1 (35 patients) had filling defects (consistent with stones) noted on operative cholangiography, which were not successfully flushed or extracted at the time of laparoscopic cholecystectomy; Group 2 consisted of patients who developed problems following laparoscopic cholecystectomy. Nine patients had post-laparoscopic cholecystectomy pain with abnormal liver function tests (LFT), four of whom had common bile duct (CBD) injuries and three had CBD stones. Eleven patients had post-laparoscopic cholecystectomy pain with a normal diameter common bile duct on ultrasound and normal LFT; only one had a CBD stone. Five patients with a persisting bile leak following laparoscopic cholecystectomy had an ERCP and endoscopic sphincterotomy. In three the leak ceased, while two required subsequent open surgery to drain bile collections and ligate the cystic duct. One patient presented with an episode of transient jaundice but had a normal ERCP. There were six post-ERCP complications; three patients had mild pancreatitis, two had a minor haemorrhage and one an asymptomatic duodenal perforation. Endoscopic retrograde cholangiopancreatography post-laparoscopic cholecystectomy was most valuable for the management of retained stones and the diagnosis and management of post-laparoscopic cholecystectomy pain in association with abnormal LFT. The diagnostic yield was low (9%) when the LFT were normal.

Adolescent↗

Projections of nerve cells from the duodenum to the sphincter of Oddi and gallbladder of the Australian possum.

BACKGROUND: This study investigated the existence of direct neural connections between the duodenum and the biliary tract in the Australian possum. METHODS: Retrogradely transported neuronal dyes, Fast Blue and Dil, were injected into the wall of the gallbladder and the sphincter of Oddi. The duodenum, biliary tract, and sympathetic and sensory ganglia were examined for the presence of labeled cell bodies. RESULTS: Two to 3 weeks after gallbladder injection, labeled nerve cell bodies were found in the myenteric plexus of the proximal duodenum but were rare in the duodenum distal to the sphincter of Oddi. No neurons were found in the submucous plexus. Labeled nerve cells were also found in the sphincter of Oddi. After injection of the sphincter, labeled neurons were in both the submucous and myenteric plexuses of the duodenum, on either side. Approximately one third of labeled myenteric neurons were immunoreactive for enkephalin. Labeled cell bodies were also in the coeliaco-mesenteric, nodose, and dorsal root ganglia after both gallbladder and sphincter injection. After a myotomy on the proximal duodenum, no neurons were labeled on the pyloric side of the lesion by subsequent sphincter injection of dye. CONCLUSIONS: Direct neural pathways connect the duodenum with the gallbladder and the sphincter of Oddi, and the sphincter with the gallbladder; this implies that enteric nerve circuits participate in coordinating duodenal and biliary functions.

Animals↗

Laparoscopic cholecystectomy for acute inflammation of the gallbladder.

OBJECTIVE: The aim of this study was to prospectively assess the results of laparoscopic cholecystectomy in patients with acute inflammation of the gallbladder. SUMMARY BACKGROUND DATA: Laparoscopic cholecystectomy has become the standard treatment for symptomatic gallbladder disease. Its role in the surgical treatment of acute cholecystitis has not been defined, although a number of recent reports suggest that there should be few contraindications to an initial laparoscopic approach. METHODS: All patients presenting with symptomatic cholelithiasis from October 1990 until June 1992 were evaluated at laparoscopy with intention of proceeding to a laparoscopic cholecystectomy. The gross appearance of the gallbladder was categorized as acute inflammation, chronic inflammation, or no inflammation. Ninety-eight (23.4%) of 418 patients had acute inflammation of the gallbladder: 55 were edematous, 10 were gangrenous, 15 had a mucocele, and 18 had an empyema. RESULTS: The authors assessed outcome in these patients. The frequency of conversion to an open operation was 33.7% for acute inflammation, 21.7% for chronic inflammation (p < 0.05), and 4% for no inflammation (p < 0.001). The conversion rate was highest for empyema (83.3%) and gangrenous cholecystitis (50%), while the conversion rate for edematous cholecystitis was 21.8% and for acute inflammation with a mucocele it was 7%. The median operation time for successful laparoscopic cholecystectomy for acute inflammation was 105 minutes, which was longer than that with no inflammation (90 minutes). However, the incidence of complications was not different from that for chronic or no inflammation. The median postoperative stay for patients with acute gallbladder inflammation was 2 days for successful laparoscopic cholecystectomy and 7 days for patients converted to an open operation. CONCLUSIONS: Laparoscopic cholecystectomy for acute inflammation of the gallbladder is safe and is associated with a significantly shorter postoperative stay compared to open surgery. A greater number of patients required conversion to open operation compared to those with no obvious inflammation. Conversion to open operation was most frequent for empyema and gangrenous cholecystitis, suggesting that once this diagnosis is made, excessive time should not be spent in laparoscopic trial dissection before converting to an open operation.

Acute Disease↗

Acute liver allograft rejection--is treatment always necessary?

A group of 195 consecutive adult patients who received a primary orthotopic liver allograft were reviewed retrospectively to analyze the incidence of rejection, the response to antirejection therapy, and the impact of acute rejection on the development of ductopenic rejection. The diagnosis of acute rejection (AR) was based on a combination of clinical and histological criteria, and 69.7% of the patients had at least one episode of acute rejection. Only 6.7% of the patients failed to respond to steroids and were treated with OKT3. Four (2.3%) patients developed acute vanishing bile duct syndrome (within 60 days) and 6 (3.5%) patients developed chronic rejection. Eight patients who spontaneously recovered from AR without additional immunosuppression are described in detail. In addition to histological damage, all developed significant hepatic dysfunction. Except for one patient who died from disseminated fungal infection, the 7 remaining patients are alive with excellent graft function 7 to 21 months posttransplant. While severe AR and recurrent AR should be treated without delay, some patients with mild-to-moderate rejection and hepatic dysfunction may resolve without additional immunosuppression.

Acute Disease↗

Steroid withdrawal from long-term immunosuppression in liver allograft recipients.

Corticosteroids were withdrawn from the immunosuppressive regimen of 168/197 (85%) of liver transplant patients who survived for more than three months. In 14, steroids were restarted for reasons other than rejection. The remaining 154 patients were evaluated for the occurrence of rejection and graft loss. Risk factors for the development of rejection after steroid withdrawal were assessed. There were 13 episodes of rejection in 12 (7.8%) grafts; 7 (4.5%) experienced acute cellular rejection, and 6 (3.9%) developed chronic ductopenic rejection. All cases of acute rejection resolved with high-dose steroids. Graft and patient loss due to chronic rejection was 3 (1.9%) and 2 (1.3%), respectively. Chronic rejection resolved in 1 patient, 1 was successfully retransplanted, and in the other 2 the principal cause of death was recurrent tumor. None of the risk factors examined (primary indication for transplant, severity of previous acute rejection, use of OKT3, retransplantation, ABO blood group donor/recipient match, CMV infection, and CsA mono versus CsA and AZA double therapy) were associated with the development of chronic rejection poststeroid withdrawal. The prevalence of side effects, after steroid withdrawal, was low; 66% of patients never required antihypertensive medication; 14% experienced a significant septic episode, and only 4 died with sepsis as the major factor. There were no fungal sepsis and no new cases of diabetes. Withdrawal of corticosteroids after 3 months can be successfully achieved in the majority of liver allograft recipients and is associated with a low rate of rejection, graft loss, and complications attributable to immunosuppressive medication.

Adolescent↗