Potential clinical and economic outcomes of CYP2C9 and VKORC1 genotype-guided dosing in patients starting warfarin therapy.

The US Food and Drug Administration has updated the label information for warfarin to encourage the use of genetic information before initiating treatment with the drug. We used decision-tree modeling to simulate the outcomes of CYP2C9 and vitamin K epoxide reductase complex 1 (VKORC1) genotype-guided dosing in patients in whom warfarin therapy is to be initiated. The inputs for the model were derived from the literature. The incremental costs per unit outcome improved (ICERs) were US$347,059 per quality-adjusted life-year (QALY) gained, $170,192 per adverse event averted, and $1,106,250 per life saved. The outcomes of 10,000 Monte Carlo simulations demonstrate that the ICER per QALY gained was >$50,000 62.1% of the time. ICER was sensitive to baseline international normalized ratio (INR) control, reduction in out-of-range INRs by genotype-guided dosing, and genotyping cost. In conclusion, genotype-guided dosing for warfarin therapy does not appear to be cost-effective, with the potential ICER per QALY being >$50,000. Lowering the genotyping cost, improving effectiveness of INR control of the genotype-guided dosing algorithm, and applying the algorithm in practice sites with high out-of-range INRs would improve the cost-effectiveness of the dosing algorithm.

Cholecystectomy or not after percutaneous cholecystostomy for acute calculous cholecystitis in high-risk patients.

BACKGROUND/AIMS: This study aims to evaluate the outcomes of percutaneous cholecystostomy for acute calculous cholecystitis in patients with high surgical risk and determine whether subsequent cholecystectomy is beneficial and necessary. Percutaneous cholecystostomy has been shown to be a safe treatment option for patients suffering from acute cholecystitis but at high risk for emergency surgery. Controversies still exist on the approach of the cholecystostomy and the subsequent management of these patients. METHODOLOGY: From January 1996 to March 2004, percutaneous cholecystostomy was performed on 65 patients that suffered from acute calculous cholecystostomy but were considered high risk for emergency surgery (American Society of Anesthesiologists grade III or IV). Their clinical outcomes were described and risk factors for in-hospital mortality and recurrence of cholecystitis were identified by univariate and multivariate analysis. RESULTS: Percutaneous cholecystostomy was successfully performed in all patients (100%). The clinical response rate was 91%. The in-hospital mortality was 12.3%. Shock on admission was found to be a single independent risk factor for in-hospital death (p=0.006; odd ratio = 16.5; 95% CI = 2.2-123.1). Twenty-four patients underwent subsequent cholecystectomy whereas 33 did not. The 1-year and 3-year recurrence of acute cholecystitis were 35% and 46% respectively in patients who did not have subsequent cholecystectomy. Stone size > or = 1cm was independently associated with higher recurrence of acute cholecystitis (p=0.01; hazard ratio = 6.3, 95% CI 1.6-25.5). However, there was no difference in 1-year and 3-year overall survival between patients with or without cholecystectomy (82% Vs 81% and 59% Vs 63%, p=0.79). CONCLUSIONS: Percutaneous cholecystostomy is a safe and promising treatment for acute calculous cholecystitis in patients who are at high risk for emergency surgery. Cholecystectomy after the resolution of cholecystitis and optimization of associated medical illnesses is always advisable in order to prevent recurrent cholecystitis. However, the limited survival of these patients because of their old age and medical co-morbidities should be taken into consideration.

Laparoscopic exploration of common bile duct in post-gastrectomy patients.

BACKGROUND/AIMS: To evaluate the results of laparoscopic exploration of the common bile duct (LECBD) in patients with previous gastrectomy. METHODOLOGY: This study is a retrospective review of a prospectively maintained database of LECBD during the period 1994-2005. Those cases of LECBD with previous open gastrectomy were sorted out and analyzed. Indications of operation included unsuccessful endoscopic extraction due to altered anatomy and some explorations were performed together with side-to-side choledochoduodenostomy so as to eliminate biliary stasis and decrease stone recurrence. The operation steps involved open insertion of trocar and creation of pneumoperitoneum, meticulous adhesiolysis, direct choledochotomy followed by clearance of biliary stones. After confirmed ductal clearance, the common bile duct was routinely closed with t-tube diversion. The perioperative parameters of these patients were analyzed and compared to those receiving open exploration of common bile duct due to previous gastrectomy during the same study period. RESULTS: Of the 184 LECBD performed between 1994 and 2005, 33 patients had previous open upper gastrointestinal operations and among them 18 LECBD were performed in post-gastrectomy patients (2 with previous classical Whipple's operation). There were 10 male and 8 female patients with mean age of 77.5 (58-97 years). Of the 14 patients undergoing preoperative endoscopic retrograde cholangiopancreatography, there were 10 failed cannulations and 4 failed extractions. Altogether 17 choledochotomies and 1 transcystic duct exploration was performed whereas 4 patients with recurrent primary stones received additional choledochoduodenostomy. Median operating time was 120 min (60-390 min). Open conversion was required in 3 patients (16.6%) because of jammed basket, extensive adhesion and "through & through" bile duct injury respectively. Postoperative complications occurred in 4 patients (22.2%), which included 3 bile leaks and also the previously mentioned bile duct injury. The median hospital stay was 9 days (4-82 days). Upon a median follow-up of 17.5 months, there was only 1 patient found to have recurrent common bile duct stone and he was managed by laparoscopic exploration and choledochoduodenostomy. When the results were compared to those 12 open explorations because of previous open gastrectomy, longer operation time (120 vs. 75 min, p=0.004) and slightly shorter hospital stay (9 vs. 14 days, p=0.104) were noted in the LECBD group but without increased complication rate (22.2 vs. 25%, p=1). CONCLUSIONS: These results suggest that LECBD is worth attempting even in patients with previous open gastrectomy.

Laparoscopic biliary bypass--a single centre experience.

BACKGROUND/AIMS: To review the results of laparoscopic biliary bypass for both benign and malignant pathologies in a minimal access surgery training center. METHODOLOGY: Retrospective review of a prospectively maintained database of laparoscopic biliary bypass during the period 1995-2004. RESULTS: During the review period 1995-2004, there were 26 laparoscopic biliary bypasses performed in our center which included 23 laparoscopic choledochoduodenostomy (LCD), 2 laparoscopic roux-en-Y choledochojejunostomy (LCJ) and 1 laparoscopic cholecystojejunostomy (LCCJ). Of the 23 LCD, all except 1 patient were operated for recurrent pyogenic cholangitis (RPC). The 2 LCJ and 1 LCCJ were performed for patients with advanced carcinoma in the periampullary region and simultaneous laparoscopic gastrojejunostomy (LGJ) was also performed to relieve the gastric outflow obstruction. Among the 23 LCD, there were 2 open conversions (7.7%) for lost broken tip of ultrasonic dissector and significant bleeding during choledochotomy respectively. Major complications occurred in 6 patients (23%), which included 3 bile leaks (11.5%), 1 intraabdominal collection (3.8%). 1 wound infection (3.8%) and 1 gastric stasis (3.8%). The only mortality in our series was a patient with carcinoma of head of pancreas undergoing simultaneous roux-en-Y LCCJ and LGJ. He had persistent gastric stasis after operation and required revision surgery for the kinked cholecystojejunostomy anastomosis. He finally died of myocardial ischemia after the second operation. As for the postoperative pain control, the mean pethidine consumption was 243.4 +/- 254.7 mg (range 0-1200 mg) and mean dologesic usage was 16.2 +/- 20.4 tablets (range 0-94 tablets). The average postoperative hospital stay was 12.6 +/- 11.5 days (range 5-60 days). The long-term functional results were satisfactory and only 1 patient had recurrent stone upon a mean follow-up of 32.3 months. Among the patients with malignant biliary obstruction, the only mishap was as previously mentioned and the remaining 2 patients could enjoy satisfactory palliation for more than a year before death. CONCLUSIONS: Laparoscopic bypass is not only feasible but also highly effective in relieving biliary obstruction with good postoperative results in both benign and malignant conditions.

Laparoscopic distal pancreatectomy: a comparative study.

BACKGROUND/AIMS: This article aims to describe the different techniques of laparoscopic distal pancreatectomy and to compare the results of our series of 9 laparoscopic resections against the historical open control in the same institution. With the advent of laparoscopic surgery, there is an increasing number of patients with different pancreatic pathologies that can now be managed by minimal access surgery. The initial results of laparoscopic pancreatectomy are quite promising particularly for those small neuroendocrine and cystic neoplasms located at the body and tail of pancreas. METHODOLOGY: The different techniques of laparoscopic distal pancreatectomy are described in detail with special emphasis on the need of "hand assistance" and the different methods of splenic preservation. The perioperative data of 9 laparoscopic distal pancreatectomies are analyzed and compared against the 5 historical open controls in the same institution. RESULTS: There were 9 laparoscopic pancreatic resections performed in our institution since 1999. Indications for surgery included 5 cystic neoplasms (1 patient with concomitant splenic artery aneurysm), 1 chronic pancreatitis with pancreatic duct stricture and a small pseudocyst, 1 pseudopancreatic tumor secondary to seal off perforated posterior gastric ulcer, 1 pseudopapillary tumor and 1 neuroendocrine tumor. There were 6 females and 3 males with median age of 61 years (range 18-79). The majority of patients was of low anesthetic risk (ASA 1 or 2). Total laparoscopic resection was performed in 7 cases and 2 resections were performed using the hand-assisting technique. Out of the 4 cases with splenic preservation, only one patient had both splenic artery and vein successfully preserved, whereas the other 3 cases had to rely on the short gastric arcade. Median operating time was 180 minutes (range 120-250) and median blood loss was 100cc (range 50-500). Pancreatic leak occurred in two patients (22.2%) and 1 patient developed intraabdominal collection, all of which settled upon conservative treatment. In our series, clear resection margin was obtained for all the neoplastic cases. Median hospital stay was 7 days (4-53). Postoperatively, patients consumed an average of 15 tablets of dologesic. No other complications were observed upon a median follow-up of 15 months (1-50). When results were compared to the 5 historical open controls (excluding those malignant tumors), patients managed with this new approach had significantly less intraoperative blood loss (100 vs. 450 mL, P = 0.021). CONCLUSIONS: Our initial experience not only confirmed the feasibility oflaparoscopic pancreatectomy, but also demonstrated the promising results of this approach in selected patients.

A single-centre experience of 40 laparoscopic liver resections.

OBJECTIVE: To review results of laparoscopic liver resections, particularly in those patients with hepatic malignancy and recurrent pyogenic cholangitis. DESIGN: Retrospective analysis. SETTING: Minimal access surgery training centre, Hong Kong. PATIENTS: Patients with pathologies located at anterio-inferio-lateral segments (Couinaud segments 2, 3, 4b, 5, 6) for laparoscopic resection were recruited during the period 1998 to 2005. Patients were excluded from review if they had: pathologies at central locations and the superior and posterior segments (4a, 7, 8), large tumours (>5 cm in diameter), and those close to major vasculature or the liver hilum. RESULTS: During the study period, we attempted 40 such laparoscopic liver resections, excluding marsupialisations and resections for simple liver cysts. There were 20 female and 20 male patients, with a mean age of 57 (standard deviation, 13; range, 29-81) years. All but one underwent a successful laparoscopic operation. Pathology included hepatocellular carcinoma (n=17), recurrent pyogenic cholangitis (n=14), colorectal liver metastasis (n=4), benign liver tumour (n=4), and intrahepatic cholangiocarcinoma (n=1). All except four were hand-assisted laparoscopic liver resections. The mean operating time was 169 (range, 60-290) minutes and mean blood loss amounted to 270 mL (range, 0-1000 mL). Complications occurred in eight (20%) patients, which included six wound infections, one postoperative bile leak, and two incisional hernias. There was no operative or hospital mortality. For hepatocellular carcinoma, clear resection (>10 mm) was achieved in all except five patients, and the 1-year and 2-year survival rates were 86% and 59% respectively. Favourable results were also obtained for resections in patients with recurrent pyogenic cholangitis; after a mean (standard deviation) follow-up of 29 (23) months, only one was readmitted (for cholangitis). CONCLUSION: In appropriately selected patients, laparoscopic liver resection is feasible and safe, and achieves acceptable survival among individuals with hepatic malignancy and very favourable long-term outcomes in those with recurrent pyogenic cholangitis undergoing hand-assisted laparoscopic segmentectomy.

Laparoscopic exploration of the common bile duct: 10-year experience of 174 patients from a single centre.

OBJECTIVES: To evaluate the role of laparoscopic exploration of the common bile duct in the management of common bile duct stones. DESIGN: Retrospective study. SETTING: Regional minimal access surgery training centre in Hong Kong. PATIENTS: Patients undergoing laparoscopic exploration of the common bile duct from 1995 to 2005. MAIN OUTCOME MEASURES: Demographic information, reasons for failed endoscopic retrograde cholangiopancreatography and open conversions, and operative morbidity and mortality. RESULTS: A total of 174 laparoscopic explorations of the common bile duct were performed. Indications for surgery (some overlapping) included: concomitant gallstones and common bile duct stones (n=68, 39%) in young persons (<60 years), previously failed endoscopic extraction (n=59, 34%), large (>2 cm) or multiple common bile duct stones (n=40, 23%), and need for laparoscopic bypass to improve bile drainage (n=34, 20%). Mean patient age was 63 (standard deviation, 16) years and 103 were female. Altogether 156 choledochotomies and 18 transcystic duct explorations were performed, with 12 (7%) open conversions. The mean operating time was 129 (standard deviation, 57) minutes. Additional procedures included: 54 laparoscopic operative cholangiographies, 34 laparoscopic biliary bypasses, and 31 instances of adhesiolysis in patients with a history of open upper gastro-intestinal surgery. Complete stone clearance was achieved in 160 (92%) patients. Non-lethal complications occurred in 34 (20%) patients and one died of sepsis after a major bile leak. The mean postoperative stay was 9 (standard deviation, 9) days. Stone recurrence ensued in seven (4%) patients after a mean follow-up of 37 (standard deviation, 29) months. CONCLUSIONS: Laparoscopic exploration of the common bile duct is highly successful and can achieve satisfactory ductal clearance even after unsuccessful endoscopic extraction and previous upper gastro-intestinal surgery. In skilled hands, for selected patients laparoscopic bypass can also achieve improved bile drainage.

Antegrade biliary stenting versus T-tube drainage after laparoscopic choledochotomy--a comparative cohort study.

BACKGROUND/AIMS: Laparoscopic exploration of the common bile duct (LECBD) has been proven to be an effective and preferred treatment approach for uncomplicated common bile duct stones. However there is still controversy regarding the choice of biliary decompression after laparoscopic choledochotomy. METHODOLOGY: This is a retrospective comparison between the use of antegrade biliary stenting and T-tube drainage following successful laparoscopic choledochotomy. During the period between January 1995 and July 2003, biliary decompression was achieved by either antegrade biliary stenting or T-tube drainage based on the discretion of the operating surgeon. For antegrade biliary stenting, a 10-Fr Cotton-Leung biliary stent was inserted through the choledochotomy and passed down across the papilla. The stent position was confirmed by on-table choledochoscopy before interrupted single-layered closure of the common bile duct. Endoscopic retrograde cholangiopancreatography (ERCP) was performed to remove the stent 4 weeks after operation and at the same time to check for any residual stones or other complications like stricture or leak. In the T-tube group, a 16-Fr latex T-tube was used and the long limb was brought out through the subcostal trocar port followed by the same method of bile duct closure. Cholangiogram through the T-tube was performed on day 7 and the tube would be taken off 1 week later (about 2 weeks after operation) if the cholangiogram did not reveal any abnormality. The two groups were compared according to the demographic data, operation time, length of hospital stay and complication rates. RESULTS: During the study period, 108 laparoscopic explorations of the common bile duct were performed in our centre of which 95 were attempted laparoscopic choledochotomies and 13 were transcystic duct explorations. Of the 95 patients with attempted laparoscopic choledochotomy, there were 9 open conversions, 17 laparoscopic bilioenteric bypasses and 6 primary closures of the common bile duct. All of these patients together with those receiving transcystic duct explorations were excluded and the remaining 63 patients having postoperative bile diversion by either antegrade biliary stenting or T-tube drainage were included in this study. Bile diversion was achieved by antegrade biliary stenting in 35 patients whereas 28 patients had T-tube drainage. There was no difference between the two groups in terms of age, clinical presentation, bilirubin level, length of hospital stay, follow-up duration, common bile duct size, size of common bile duct stones, incidence of residual/recurrent stone and complication rate. It was observed that more patients in the stenting group developed bile leak (14.2% vs. 3.5%) and required more intramuscular pethidine injections (182.86 +/- 139.30 vs. 92.81+/-81.15mg, P=0.000). On the other hand, the T-tube group had longer operation time (141.4+/-45.1 vs. 11 1.1+/-33.9 minutes, P=0.006) and had a longer postoperative hospital stay (10.0+/-7.4 vs. 8.8+/-9.3 days, P=0.020) reaching statistical significance. CONCLUSIONS: Postoperative bile diversion by antegrade biliary stenting after laparoscopic choledochotomy is shown to shorten operation duration and postoperative stay as compared to T-tube drainage, but the problem of bile leak needs further refinement of insertion technique.

Laparoscopic management of acute torsion of the omentum in adults.

BACKGROUND: Acute torsion of the greater omentum is a rare cause of acute abdomen in adults. We report our experience on the clinical presentation, diagnosis, treatment, and outcome of this condition. METHOD: This is a retrospective review of 9 patients who had a clinicopathologic diagnosis of acute torsion of the greater omentum and were treated at the Department of Surgery, Pamela Youde Nethersole Eastern Hospital from January 1994 to March 2004. Eight patients were male and 1 was female with a median age of 43 years (range, 24 to 65). Median body mass index was 24 kg/m(2) (range, 22 to 24). All presented with acute abdominal pain with a median temperature of 36.8 degrees C (range, 36.5 to 37.2) and a median white cell count of 9.5 x 10(9)/L (range, 7.4 to 15.1 x 10(9)). Preoperative ultrasound was done in 5 patients. RESULTS: All diagnoses were made during surgery. Resection of the infarcted omentum was performed for all patients (5 laparoscopic resections and 4 open resections). No postoperative complications occurred. The overall median time from admission to operation was 23 hours (range, 2 to 98). The overall median operating time and postoperative stay were 70 minutes (range, 38 to 105) and 3 days (range, 1 to 6), respectively. The median oral and parenteral analgesic requirement for postoperative pain control was less and the median hospital stay was shorter in patients who underwent laparoscopic resection. CONCLUSION: Acute torsion of the greater omentum is an uncommon cause of acute abdomen in adults, and preoperative diagnosis is usually difficult. Laparoscopy seems a safe and minimally invasive technique for both diagnosis and treatment of this rare disease entity.

Laparoscopy versus open left lateral segmentectomy for recurrent pyogenic cholangitis.

BACKGROUND: Recurrent pyogenic cholangitis (RPC) is a common disease in Southeast Asia. Its classical presentation is repeated attacks of cholangitis with multiple recurrences of bile duct stones. The stones are commonly located in the left lateral segments (2 and 3) and therefore complete clearance is difficult to achieve by either endoscopic retrograde cholangiopancreatography or surgical exploration of the common bile duct. The definitive treatment usually involves resection of the stone-harboring segments. The recent advent in laparoscopic surgery has shown that hand-assisted laparoscopic segmentectomy is a safe and feasible, alternative. This study aimed to compare hand-assisted laparoscopic segmentectomy with open segmentectomy in patients with recurrent, RPC. METHODS: This study retrospectively reviewed a prospectively maintained database of both open and laparoscopic treatments for RPC in a single center between 1994 and 2004. During this period, patients with RPC and left intrahepatic (segments 2 and 3) ductal stones not amendable to endoscopic treatment were recruited for analysis. Patients with concomitant gallbladder stones and common bile duct stones were offered left lateral segmentectomy with cholecystectomy and exploration of the common bile duct. Selected patients would have choledochoduodenostomy drainage during the same operation. The operations were performed via either the hand-assisted laparoscopic approach or the open approach using an ultrasonic surgical aspirator. The two cohorts were compared with respect to perioperative parameters to determine whether there would be any advantage in attempting hand-assisted laparoscopic segmentectomy. RESULTS: During the study period from 1994 to 2004, 17 patients underwent left lateral segmentectomy for RPC. Of the 17 patients, 10 had hand-assisted laparoscopic resections, and 7 underwent open resections. All open resections were performed before 1999. Despite the small number of patients and potential type 2 error, there were no differences in age, sex distribution, number of cholangitic attacks, sessions of endoscopic retrograde cholangiopancreatography before surgery, or number of previous operation between the two groups. The median operating time was shorter in the open group (232.5 vs 150 min; p = 0.007), whereas the median blood loss was similar (350 vs 400 ml; p = 0.551). The median postoperative stay was 8 days for hand-assisted laparoscopic group versus 14 days for the open group. This difference was statistically significant (p = 0.019). There was one open conversion in the hand-assisted laparoscopic group because of intraoperative bleeding from the left hepatic vein. Postoperative complication rates were lower in hand-assisted laparoscopic group, but the difference was not statistically significant (20% vs 57%; p = 126). The intramuscular pethidine requirement again was less in hand-assisted laparoscopic group (0 vs 600 mg; p = 0.002). There was no operative mortality in either group of patients. No recurrent cholangitis was noted in either groups during the median follow-up period of more than 3 years. CONCLUSION: This study not only confirmed the feasibility of hand-assisted laparoscopic segmentectomy for recurrent pyogenic cholangitis, but also showed that this treatment approach is associated with less pain and shorter hospital stay. However, hand-assisted laparoscopic segmentectomy is a lengthier operation and technically more challenging. Nevertheless, the authors believe that with more experience and further improvement of ancillary technology, this procedure can become a standard treatment for recurrent pyogenic cholangitis in selected cases.

A double-blind, randomized trial comparing Ligasure and Harmonic Scalpel hemorrhoidectomy.

PURPOSE: The major problem after hemorrhoidectomy is postoperative pain. New techniques have been evolved to circumvent this problem. The present study was conducted to compare the outcomes of Ligasure hemorrhoidectomy and Harmonic Scalpel hemorrhoidectomy. METHODS: This study was a double-blind, randomized controlled trial. Patients with Grade 3 and 4 hemorrhoids admitted for hemorrhoidectomy were selected and randomized into two groups: 1) Ligasure hemorrhoidectomy or 2) Harmonic Scalpel hemorrhoidectomy. The primary outcomes measured were the analgesic requirement and the postoperative pain score (assessed by an independent assessor). Secondary outcome criteria included the operating time, blood loss, hospital stay, patient satisfaction score, and early and late complications. RESULTS: Forty-nine patients were randomized into two groups (LigaSure 24, Harmonic Scalpel 25). Two patients were lost to follow-up, leaving 47 patients (LigaSure 24, Harmonic Scalpel 23) available for final analysis. The age and gender distribution were comparable. The postoperative pain score (median 2.6 vs. 4.8, P < 0.001) and postoperative oral analgesic (Dologesic) requirement (median 5 vs. 13, P = 0.001) were significantly less in the LigaSure group. The operating time (median 11 vs. 18 minutes, P < 0.001) was significantly less in the LigaSure group. The hospital stay, patient satisfaction score, percentage of patients requiring pethidine injection, percentage of patients with first bowel movement on or before the first postoperative day, and complication rates were similar between the two groups. CONCLUSIONS: Ligasure hemorrhoidectomy reduces the postoperative pain and operating time compared to the Harmonic Scalpel hemorrhoidectomy. It is a safe, effective procedure for treating Grade 3 and 4 hemorrhoids.

Non-prostanoid prostacyclin mimetics as neuronal stimulants in the rat: comparison of vagus nerve and NANC innervation of the colon.

The spontaneous activity of the rat isolated colon is suppressed by prostacyclin analogues such as cicaprost (IC(50)=4.0 nM). Activation of prostanoid IP(1)-receptors located on NANC inhibitory neurones is involved. However, several non-prostanoids, which show medium to high IP(1) agonist potency on platelet and vascular preparations, exhibit very weak inhibitory activity on the colon. The aim of the study was to investigate this discrepancy. Firstly, we have demonstrated the very high depolarizing potency of cicaprost on the rat isolated vagus nerve (EC(50)=0.23 nM). Iloprost, taprostene and carbacyclin were 7.9, 66, and 81 fold less potent than cicaprost, indicating the presence of IP(1) as opposed to IP(2)-receptors. Three non-prostanoid prostacyclin mimetics, BMY 45778, BMY 42393 and ONO-1301, although much less potent than cicaprost (195, 990 and 1660 fold respectively), behaved as full agonists on the vagus nerve. On re-investigating the rat colon, we found that BMY 45778 (0.1 - 3 microM), BMY 42393 (3 microM) and ONO-1301 (3 microM) behaved as specific IP(1) partial agonists, but their actions required 30 - 60 min to reach steady-state and only slowly reversed on washing. This profile contrasted sharply with the rapid and readily reversible contractions elicited by a related non-prostanoid ONO-AP-324, which is an EP(3)-receptor agonist. The full versus partial agonism of the non-prostanoid prostacyclin mimetics may be explained by the markedly different IP(1) agonist sensitivities of the two rat neuronal preparations. However, the slow kinetics of the non-prostanoids on the NANC system of the colon remain unexplained, and must be taken into account when characterizing neuronal IP-receptors.

Changes in refractive trends and optical components of Hong Kong Chinese aged over 40 years.

The age trends of refractive errors, astigmatism and optical components were studied in 220 Chinese subjects aged over 40 years. Myopia did not dominate in this age group. With increasing age, the prevalence of hyperopia increases from 2% at age 40-45 years to 66% at age > 65 years. Against-the-rule astigmatism was more prevalent than the other types. Significant correlations were found between age and spherical equivalent power, age and vitreous depth and axial length. Sex differences were found among the optical components but not in the refractive error. Myopia appears to be more prevalent among the younger age groups than the older age groups of the Hong Kong Chinese population, and the importance of genetics in determination of refractive error is called into question by these findings.