A comparison of dabigatran and warfarin for stroke prevention in elderly Asian population with nonvalvular atrial fibrillation: An audit of current practice in Malaysia.

INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia with significant morbidity and mortality in relation to thromboembolic stroke. Our study aimed to evaluate the safety and efficacy of dabigatran in stroke prevention in elderly patient with nonvalvular AF with regard to the risk of ischemic stroke and intracranial haemorrhage (ICH) in real-world setting. METHODS: A retrospective cohort study of 200 patients on dabigatran and warfarin from January 2009 till September 2016 was carried out. Data were collected for 100 patients on dabigatran and 100 patients on warfarin. RESULTS: The mean follow-up period was 340.7±322.3 days for dabigatran group and 410.5±321.2 days for warfarin group. The mean time in therapeutic range (TTR) was 52±18.7%. The mean CHA2DS2 -VASc score for dabigatran group was 4.4±1.1 while 5.0±1.5 for warfarin group. None in dabigatran group experienced ischemic stroke compared to one patient in warfarin group (p=0.316). There was one patient in dabigatran group suffered from ICH compared to none in warfarin group (p=0.316). Four patients in warfarin group experienced minor bleeding, while none from dabigatran group (p=0.043). CONCLUSION: Overall bleeding events were significantly lower in dabigatran group compared to warfarin group. In the presence of suboptimal TTR rates and inconveniences with warfarin therapy, non-vitamin-K antagonist oral anticoagulants (NOAC) are the preferred agents for stroke prevention in elderly Asian patients for nonvalvular AF.

Persistent thrombocytopenia following dengue fever: What should we do?

Thrombocytopenia is a common laboratory finding in dengue infection. However, it usually resolves as the patient recovers from the infection. Persistent thrombocytopenia following dengue infection requires further investigation. Here, we present a case of immune thrombocytopenic purpura (ITP) following dengue infection complicated by intracranial bleeding.

Gaseous emboli detection based on a dual-wavelet transform analysis.

Emboli monitoring is nowadays based on the assessment of microembolic signals by Doppler ultrasound. However, the present systems have problems in detecting multiple emboli. A more dedicated algorithm for post-processing of the recorded Doppler signals was proposed. Based on the hypothesis that single and multiple gaseous emboli can be quantified by combining discrete and continuous wavelet transformation, the aim of this study was to detect gaseous emboli and to validate our method visually. A flow rig was used where gaseous emboli were generated. Doppler signals and visual validation data of gaseous emboli were acquired simultaneously. Microembolic signals were extracted and analysed using wavelet transformation. Results were validated against a visual reference. At various degrees of bubble generation, the system had 100 per cent detection during a low frequency of bubble generation but an estimation error of 7.4 per cent during a high frequency of bubble generation. The estimation error varied between -7.4 and +3 per cent. The system had a higher rate of success in detecting large gaseous emboli in small numbers than small gaseous emboli in large numbers. Single and double emboli were successfully detected and separated, whereas gaseous emboli clouds could be detected but not quantified. Being able to separate simultaneous gaseous emboli may offer new means of increasing detectability for embolism monitoring.

Isolation of a single strain of Helicobacter pylori from the antrum and body of individual patients.

OBJECTIVES: This study aimed to determine intra-patient colonization patterns of Helicobacter pylori strains based on DNA fingerprinting and antibiotic susceptibility. METHODS: Two biopsies, one from the antrum and one from the body of the stomach, were taken from 97 patients. Prior informed consent was obtained. The status of cagA gene of H. pylori strains was analysed by using the polymerase chain reaction (PCR) technique, while DNA fingerprints were generated by PCR-based, random amplified polymorphic DNA (RAPD) fingerprinting. The antibiotic susceptibility of the H. pylori isolates was examined by the disk diffusion method. RESULTS: A total of 51 pairs of H. pylori strains were isolated from both antrum and body specimens of 51 patients. This included two patients who were endoscoped twice because of treatment failure. All strains were positive for cagA gene by PCR. These 51 patients were found to harbour a single strain of H. pylori with identical or highly similar DNA profiles by PCR-based RAPD fingerprinting. In four of the 51 pairs, the DNA patterns of H. pylori from antrum and body showed minor differences, while three pairs of strains with different metronidazole sensitivities showed identical DNA fingerprints. Interestingly, the two treatment failure patients remained colonized with the strains that had the same RAPD fingerprinting patterns before and after treatment. CONCLUSION: The present study demonstrates that a single H. pylori strain colonizes a single stomach. However, this single genotypic strain may exhibit different metronidazole susceptibility in different parts of stomach.

Helicobacter pylori infection is unlikely to be transmitted between partners: evidence from genotypic study in partners of infected patients.

INTRODUCTION: We postulated that the oro-oral route of transmission between spouses could be an important route of transmission of Helicobacter pylori. AIMS: To estimate the prevalence of different genotypes of H. pylori as distinguished by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in our local population, and to compare the genotypes of H. pylori isolated from patients and their spouses. METHODS: Gastric biopsies were obtained from 183 dyspeptic patients during endoscopy. PCR for H. pylori was carried out using the uceC gene for amplification, and PCR products were digested further for RFLP analysis using the enzyme MboI. Spouses of H. pylori-positive index cases were screened for the infection using serological testing; if found to be positive serologically, endoscopy and gastric biopsies were performed for genotypic study of the micro-organism. For couples with indistinguishable H. pylori strain on RFLP with restriction endonuclease MboI, the process of RFLP was repeated with digestion of the PCR products using restriction endonuclease HhaI. RESULTS: We established our PCR technique to be 89.5% sensitive and 95.5% specific. Eighty-nine subjects were found to be H. pylori positive by PCR, and eight different genotypic strains were found according to our RFLP analysis. Two genotypes accounted for 80.8% of the cases. Sixteen of 31 spouses tested serologically for H. pylori were positive. All 13 spouses who agreed to undergo endoscopy were PCR positive for H. pylori. Five couples shared indistinguishable H. pylori genotypes, but this strain was also the commonest genotype in our local population, as based on RFLP with restriction endonuclease MboI. Further RFLP on the PCR products on these five couples using restriction endonucleases HhaI showed that the H. pylori isolated from these five couples were of different strains. CONCLUSION: The oro-oral route of transmission between spouses is unlikely to be an important mode for H. pylori infection.

Bioadhesive polymers as platforms for oral controlled drug delivery II: synthesis and evaluation of some swelling, water-insoluble bioadhesive polymers.

A series of cross-linked, swellable polymers was sythesized from monomers such as acrylic acid, methacrylic acid, and others with various cross-linking agents to produce a range of polymers differing in charge densities and hydrophobicity. The densities, rate, and extent of hydration of the polymers were determined. An increase in the number of hydrophobic groups in the polymer structure reduced hydration whereas the density of the polymer was unaffected. A sensitive in vitro method for measuring adhesion of polymer to tissue from the rabbit stomach was developed. Polymers of acrylic acid loosely cross-linked (0.3%, w/w) with three different agents, divinyl glycol, 2,5-dimethyl-1,5-hexadiene, and divinylbenzene, showed the same degree of bioadhesion while poly(methacrylic acid-divinylbenzene) showed reduced bioadhesion. The small percent of cross-linking agent, irrespective of physicochemical properties, did not contribute substantially to bioadhesion, whereas the starting monomer had a large effect. The effect of pH on the bioadhesion of poly(acrylic acid-divinyl glycol) was studied at constant temperature, ionic strength, and osmolality. The polymer showed maximum adhesion at pH 5 and 6 and a minimum at pH 7. Gastrointestinal transit studies of cross-linked polymers in rats were studied. Poly(acrylic acid-divinyl glycol) and poly(methacrylic acid-divinylbenzene) were shown to have substantially longer GI transit times than the control, Amberlite 200 resin beads. The delay in transit time was due to bioadhesion of the polymer to the mucin-epithelial cell surface which was clearly observable on animal autopsy. The acrylic acid polymer showed a longer GI transit time than the methacrylic acid polymer, and this in vivo GI transit result is consistent with in vitro bioadhesion test results.

Bioadhesive polymers as platforms for oral controlled drug delivery III: oral delivery of chlorothiazide using a bioadhesive polymer.

Bioadhesive polymers that bind to the gastric mucin or epithelial cell surface are useful in drug delivery for the purposes of (a) retaining a dosage from in the GI tract and (b) increasing the intimacy and duration of contact of drug with the absorbing membrane. Polycarbophil has previously been shown to have bioadhesive properties in the rat stomach and small intestine and was employed in the present study with a sustained-release delivery system to demonstrate improved drug delivery. Using chlorothiazide as the model drug, drug containing albumin beads were prepared and used as the sustained-release system. The beads were physically mixed with equally sized particles of polycarbophil and placed in a capsule to produce a bioadhesive dosage form. When the dosage form contacts the stomach, the gelatin capsule dissolves, exposing the polycarbophil to the bathing fluid. The bioadhesive polymer rapidly hydrates, retaining the albumin beads and attaching to the mucin coating of the stomach. Plasma drug levels in rats showed a longer duration of action and greater bioavailability for the bioadhesive dosage form than for either albumin beads or drug powder alone. The results suggest that the principle of bioadhesion can significantly improve therapy, due to a reduced rate of gastric emptying, an increase in contact time, and the intimacy of contact of the drug with the absorbing membrane.

Analog and digital FPGA implementation of BRIN for optimization problems.

The binary relation inference network (BRIN) shows promise in obtaining the global optimal solution for optimization problem, which is time independent of the problem size. However, the realization of this method is dependent on the implementation platforms. We studied analog and digital FPGA implementation platforms. Analog implementation of BRIN for two different directed graph problems is studied. As transitive closure problems can transform to a special case of shortest path problems or a special case of maximum spanning tree problems, two different forms of BRIN are discussed. Their circuits using common analog integrated circuits are investigated. The BRIN solution for critical path problems is expressed and is implemented using the separated building block circuit and the combined building block circuit. As these circuits are different, the response time of these networks will be different. The advancement of field programmable gate arrays (FPGAs) in recent years, allowing millions of gates on a single chip and accompanying with high-level design tools, has allowed the implementation of very complex networks. With this exemption on manual circuit construction and availability of efficient design platform, the BRIN architecture could be built in a much more efficient way. Problems on bandwidth are removed by taking all previous external connections to the inside of the chip. By transforming BRIN to FPGA (Xilinx XC4010XL and XCV800 Virtex), we implement a synchronous network with computations in a finite number of steps. Two case studies are presented, with correct results verified from simulation implementation. Resource consumption on FPGAs is studied showing that Virtex devices are more suitable for the expansion of network in future developments.

Survey of dyspepsia management in community.

INTRODUCTION: Dyspepsia is a common complaint and represents an important health problem in the community. The aim of the study was to survey the diagnostic approach and management of dyspepsia and Helicobacter pylori (H. pylori) infection by primary care physicians. METHODS: Questionnaires were given to 70 medical officers (MO) working in government polyclinics and 70 general practitioners (GP) in private practice. RESULTS: Questionnaires were returned from 68 MO's (response rate 97%) and 61 GP's (response rate 87%). Only 20% of MO and 50% of GP prescribed H. pylori eradication therapy. Of those who have prescribed eradication therapy, 70% would confirm H. pylori infection before therapy (50% for gastroscopy, 19% for Urea Breath test, 25% for laboratory based serology, 6% for office based serology test kits). 85% would prescribe triple therapy against 15% for dual therapy. Proton pump inhibitor (PPI) is the acid suppression agent most commonly prescribed (77%) in regimens of eradication therapy; the remaining would prescribe either bismuth subcitrate or H2 antagonists. Only 8% of respondents would confirm eradication after therapy. CONCLUSION: Less than half of the primary care physicians surveyed prescribed H. pylori eradication therapy. The main reason given for not prescribing therapy was lack of facility for testing the infection. Of those who prescribed eradication therapy, majority would order the correct and reliable investigations to confirm the infection. Most of them would prescribe triple therapy which is the recommended eradication regimens.

Discussion of an interesting case of Crohn's disease.

An interesting case of Crohn's disease is discussed whose initial presentation and diagnosis was that of irritable bowel syndrome. The key points in this case were the change in symptoms with time, the presence of alarm symptoms such as loss of weight, bleeding per rectum and tenesmus. The indication for further diagnostic investigations whether invasive or not is a lesson to learn.

One week triple therapy for Helicobacter pylori associated duodenal ulcer disease.

INTRODUCTION: Eradication of Helicobacter pylori (H. pylori) cures and prevents the relapse of duodenal ulceration. Different treatment regimes for the eradication of H. pylori have been used and the most successful eradication regimens have been one week treatments with a proton pump inhibitor and two antibiotics. AIM OF STUDY: To examine the eradication rate of H. pylori with a one week regimen consisting of OCT (Omeprazole 20 mg BD, Clarithromycin 250 mg BD, Tinidazole 500 mg BD). This treatment regimen has been used for H. pylori eradication in our department since the end of 1996. METHODS: Patients diagnosed to have duodenal ulcer in 1997 were retrospectively reviewed. Infection with H. pylori must be documented either by gastric biopsy or by a positive CLO test. Eradication of H. pylori was confirmed by negative 14C urea breath test or by histology at least four weeks after cessation of therapy. RESULTS: The review was performed on 251 patients. There were 177 males, 74 females. The median age was 51 (18-77) years. H. pylori infection was confirmed by CLO test in 170 patients and by histology in 72 patients. Thirty patients did not undergo further investigation after therapy to confirm the eradication. Of the remaining 221 patients, H. pylori was successfully eradicated in 198 patients (89.6%) as confirmed by 14C urea breath test (190 patients) or repeat gastroscopy and gastric biopsy (31 patients). There were no serious adverse events documented. CONCLUSIONS: Our retrospective study showed that the one week regimen used in our department is effective for the eradication of H. pylon in nearly 90% of infected cases.

A case of small cell carcinoma with ectopic ACTH syndrome.

We report a case of ectopic ACTH syndrome in a 50-year old woman with small cell carcinoma of the lung. Ectopic ACTH syndrome from small cell carcinoma often presents with hypokalemia, metabolic alkalosis and muscle wasting. This patient presented with Cushingnoid features which is unusual in such cases.

Case report--melanoma of the anorectum.

Melanomas of the gastrointestinal tract are rare tumours, the anorectum being the most common site. Anorectal melanomas can pose difficult diagnostic and therapeutic problems. Awareness on the part of both the clinician and histopathologist that melanomas can rarely occur in the anorectum is an important pre-requisite to its diagnosis as specific histopathological staining may be required. Therapeutically, surgery remains the primary option. Prognosis is however poor as metastatic disease is commonly established at presentation. When the tumour is sited in the rectum, the cells of origin is controversial. A case of disseminated anorectal melanoma is described.

Gastrointestinal manifestations of systemic lupus erythematosus.

Gastrointestinal symptoms are common in patients with systemic lupus erythematosus (SLE) and can be due to primary gastrointestinal disorders, complications of therapy or SLE itself. In this case report, we describe three different presentations and causes of gastrointestinal complaints in patients with SLE. Diagnostic and management problems are discussed.

Efficacy of a nitroimidazole containing tripletherapy regime in Singapore.

BACKGROUND: There has been a gradual increase in the proportion of Singapore patients with metronidazole resistant strains of Helicobacter pylori. We studied the efficacy of a nitroimidazole containing regime in eradicating H. pylori. METHODS: Consecutive treatment naive patients with peptic ulcer disease and culture proven H. pylori were recruited. From each patient, two antral biopsies were taken for rapid urease test and two for histology. Two biopsies each from the gastric antrum and corpus were taken for H. pylori culture. Antibiotic sensitivity to amoxycillin, metronidazole, clarithromycin and tetracycline were tested using the disc diffusion method. Patients were treated with lansoprazole 30 mg bd, tinidazole 500 mg bd and clarithromycin 500 mg bd for seven days. Successful eradication was defined as either negative urea breath tests 4 and 12 weeks after treatment, or negative histology and culture at least four weeks after the end of treatment. RESULTS: A total of 64 patients were culture positive (51 males, 13 females). Forty-two patients had duodenal ulcers (DU), 17 gastric ulcers (GU), and 5 DU and GU. Metronidazole resistance was detected in 16 patients (25%). Three of the 16 patients (19%) had a mixed population of resistant and sensitive strains of H. pylori. None of the H. pylori isolates were resistant to amoxycillin, tetracycline or clarithromycin. Overall, eradication was achieved in 51/64 patients (80%). Eradication rate was 88% (42/48) among those with metronidazole sensitive strains, and 56% (9/16) among those with metronidazole resistant strains (p < 0.02). CONCLUSION: A high proportion of our patients with metronidazole resistant strains of H. pylori failed eradication therapy when a nitroimidazole containing regime was used. It may not be appropriate to use a nitroimidazole containing without prior knowledge of the antibiotic sensitivity pattern of the H. pylori isolate.

Apparent change of Rhesus blood group typing in a case of ulcerative colitis.

An interesting case of ulcerative colitis with an apparent change of Rhesus blood group typing is described. To our knowledge, this has not been reported before. We postulate that during the initial active phase of ulcerative colitis, an unknown D-like antigen, possibly bacterial in origin, could temporarily give rise to a Rhesus D-positive blood group typing in a patient with Rhesus D-negative blood type. Interestingly, with continuous immunosuppressive therapy for ulcerative colitis, the patient did not develop anti-D antibodies despite multiple transfusions with D-positive blood.

Role of ERCP in the management of bile duct lesions post bile duct surgery.

INTRODUCTION: Therapeutic Endoscopic Retrograde Cholangio-Pancreatography (ERCP) is an established mode of treatment for bile duct lesions. AIM: This paper reviews the role of ERCP in the management of bile duct lesions developing after biliary surgery. PATIENTS AND METHODS: Of the 894 ERCPs performed in our department between January 1990 and May 1992, 23 (13 female, 10 male) were for patients with post-operative bile duct lesions. The mean age of these 23 patients was 59 years (range 38-91 years). The previous biliary surgical procedures were conventional cholecystectomy (n = 19), laparoscopic cholecystectomy (n = 3) and a cholecystectomy with choledochojejunostomy. Associated medical conditions of ischaemic heart disease, unstable angina, hypertensive heart disease, chronic obstructive airway disease and hepatitis B cirrhosis were present in 7 of these patients. RESULTS: Ten patients had benign biliary strictures. Endoscopic stenting (with one or 2 stents) was successful in 9. The strictures reopened in 2 patients after a total stenting duration of 12 and 18 months respectively. Four patients had biliary leakages that were successfully treated with stenting. Two patients had spontaneous sealing of biliary leak at 3 and 6 months respectively. Nine patients had retained stones (7 with solitary stone, 2 with multiple stones) that were successfully removed with Dormia basket after sphincterotomy. Complications were few and manageable. CONCLUSIONS: Therapeutic ERCP is safe and effective. It is a useful adjunct in the management of patients with post-operative biliary lesions.

Extrahepatic bile duct length in the Singapore population.

BACKGROUND: Although the length of the common bile duct is well documented, the length of extrahepatic biliary tree is less well studied, particularly in among the Asian population. The extrahepatic bile duct (BD) length is defined as the measurement from the hepatic hilum to the papilla. OBJECTIVE: This study was performed to assess the normal range of extrahepatic BD length, as defined above, in the Singapore population. This information would be useful in assisting the local endoscopy unit in procuring the different lengths of biliary stents. METHOD: Between 1.8.96 to 1.12.97, 486 cholangiograms were obtained post-ERCP, of which only 100 cholangiograms that were representative of a non-distorted BD were used for analysis. The BD length, taken from the mid-point of the confluence of the left and right hepatic ducts at the hilum to the papilla, was measured with a string placed on the cholangiogram. The true length was obtained after correction for radiological magnification. RESULTS: The range of bile duct lengths followed a normal distribution curve with a mean length of 9.6 cm. The range was from 6.9 cm to 12.6 cm. With respect to the length of stents commonly deployed, the cumulative percentage of BD length less than and equal to 7-, 9-, 10- and 12-cm were 1%, 38%, 57% and 98% respectively. CONCLUSION: From a practical point of view, this study suggests that endobiliary stent of 5 cm in length should be readily available for drainage of distal CBD strictures as 1% of our population has BD length less than 7 cm. However, as 2% of the population has BD length greater than 12 cm, 15 cm stents should be available in the endoscopy unit for drainage of hilar obstructions/strictures.

Primary leiomyoma of the liver.

This case report describes a primary hepatic leiomyoma presenting as a mass lesion detected on ultrasonography of the abdomen in an asymptomatic hepatitis B carrier on routine surveillance. Primary leiomyomata of the liver are rare occurrences, with only 9 cases reported in the literature. The presenting features of primary hepatic leiomyomata and diagnostic approach towards such lesions are discussed. The significance of such tumours in the immunocompromised is also mentioned.

A randomised trial of amoxycillin versus clarithromycin in combination with omeprazole for eradication of Helicobacter pylori infection in Singapore.

Dual therapy has been reported to produce H.pylori eradication rate of 75-80%. This study is designed to determine the efficacy of omeprazole 20 mg bd in combination with amoxycillin 500 mg tid (Group A), amoxycillin 750 mg tds (Group B) and clarithromycin 500 mg tid (Group C) in Singapore. One hundred and forty-eight patients with H. pylori positive duodenal ulcers between ages of 22 and 69 were enrolled from two centres. There were 48 patients in Group A, 50 patients in Group B and 50 patients in Group C. The medication was given for 14 days. The patients were re-evaluated with an upper GI endoscope 4 weeks after cessation of treatment Successful eradication was defined as H.pylori negative on histology and culture. Based on intention to treat analysis, the eradication rate was 47.8% in Group A, 68% in Group B and 66% in Group C. The difference between GroupA and B were statistically significant (p = 0.04). Based on all patient treated analysis, the eradication rate was 57.5% in Group A, 70.7% in Group B and 75% in Group C. The difference in eradication rates was not statistically significant. Adverse events were reported in 21% of all patients with no difference in the adverse event rate between all groups. The eradication rate achieved with dual therapy in this study was similar to that attained in Western population. Higher dose amoxycillin regime gives a significantly higher eradication than a lower dose amoxycillin.