Use of biologics for inflammatory bowel disease in Hong Kong: consensus statement.

UNLABELLED: OBJECTIVE; With the increasing use of biologics in patients with inflammatory bowel disease, the Hong Kong IBD Society developed a set of consensus statements intended to serve as local recommendations for clinicians about the appropriate use of biologics for treating inflammatory bowel disease. PARTICIPANTS: The consensus meeting was held on 9 July 2011 in Hong Kong. Draft consensus statements were developed by core members of the Hong Kong IBD Society, including local gastroenterologists and colorectal surgeons experienced in managing patients with inflammatory bowel disease. EVIDENCE: Published literature and conference proceedings on the use of biologics in management of inflammatory bowel disease, and guidelines and consensus issued by different international and regional societies on recommendations for biologics in inflammatory bowel disease patients were reviewed. CONSENSUS PROCESS: Four core members of the consensus group drafted 19 consensus statements through the modified Delphi process. The statements were first circulated among a clinical expert panel of 15 members for review and comments, and were finalised at the consensus meeting through a voting session. A consensus statement was accepted if at least 80% of the participants voted "accepted completely or "accepted with some reservation". CONCLUSIONS: Nineteen consensus statements about inflammatory bowel disease were generated by the clinical expert panel meeting. The statements were divided into four parts which covered: (1) epidemiology of the disease in Hong Kong; (2) treatment of the disease with biologics; (3) screening and contra-indications pertaining to biologics; and (4) patient monitoring after use of biologics. The current statements are the first to describe the appropriate use of biologics in the management of inflammatory bowel disease in Hong Kong, with an aim to provide guidance for local clinical practice.

Hong Kong experiences the 'Ultimate superbug': NDM-1 Enterobacteriaceae.

We report the second imported case of New Delhi metallo-beta-lactamase (NDM-1) Enterobacteriaceae encountered in Hong Kong soon after the patient's arrival in the territory for medical care. As NDM-1 is spreading throughout the world via international travel, being an international city, Hong Kong was always expected to encounter the same public health threat. This case also illustrates the importance of active surveillance of at-risk patients in preventing the spread of this 'superbug'.

Evaluation of in-house and commercial genotyping assays for molecular typing of hepatitis C virus in Hong Kong.

This study aims to evaluate genotyping assays for hepatitis C virus (HCV). An in-house nucleic acid sequencing method is performed in parallel with the Roche Linear Array HCV genotyping test on 73 HCV-positive (66 clinical samples and seven proficiency testing quality control samples) and 12 HCV-negative samples (11 clinical samples and one proficiency testing sample). The performance of the in-house method was comparable with that of the Roche assay (concordance rate: 89.4%). Discordant results included four mixed infections missed by the in-house method, two false-negatives with the Roche assay, and three discrepant results. The in-house method exhibited a higher resolution (subtype vs. genotype level) at a lower running cost (25% of the commercial assay). The in-house method was also used to genotype 375 HCV clinical isolates to determine the genotypic distribution of HCV in Hong Kong between 2005 and 2008. A total of 441 (52.8%) clinical isolates proved to be genotype 1, which shows a poorer response to interferon therapy. Genotype 6 was the next most common (32.0%). Prevalence of genotypes 2 and 3 was 7.7% and 6.6%, respectively, and prevalence of genotypes 4 and 5 was 0.9% and 0%, respectively. Although the in-house nucleic acid sequencing method failed to detect a few cases of mixed HCV infection, its high resolution and low running cost make it suitable for surveillance and outbreak investigation.

Role of polymorphisms of the inflammatory response genes and DC-SIGNR in genetic susceptibility to SARS and other infections.

1. A genetic risk-association study involving more than 1200 subjects showed individuals homozygous for L-SIGN tandem repeats are less susceptible to SARS infection. 2. This was supported by in vitro binding studies that demonstrated homozygous L-SIGN, compared to heterozygous, had higher binding capacity for SARS coronavirus (SARS-CoV), with higher proteasome-dependent viral degradation. In contrast, homozygous L-SIGN demonstrated lower binding capacity for HIV1-gp120.3. Genetic-association studies for single nucleotide polymorphisms of the inflammatory response genes, namely TNF-alpha, INF-alpha, INF-beta, INF-gamma, IL1-alpha, IL1-beta, IL-4, IL-6 and iNOS, failed to show a significant association with SARS clinical outcomes or susceptibility.

Disease progression in Chinese chronic hepatitis C patients with persistently normal alanine aminotransaminase levels.

BACKGROUND: Although chronic hepatitis C virus-infected patients with persistently normal alanine aminotransaminase levels usually have mild liver disease, disease progression can still occur. However, it is uncertain which group of patients is at risk of disease progression. AIM: To examine the severity of liver disease on liver biopsy in Chinese patients with persistently normal alanine aminotransaminase levels, and their disease progression over time. METHODS: Eighty-two patients with persistently normal alanine aminotransaminase levels were followed up longitudinally. The median time of follow-up was 8.1 years. Forty-seven of the 82 patients (57.3%) had a second liver biopsy. RESULTS: At the time of analysis, six of the 82 patients (7.3%) developed decompensated liver cirrhosis. Patients with an initial fibrosis stage F2 or F3 [6/23 (26.1%) vs. 0/59 (0%), P < 0.0001] or inflammatory grade A2 or A3 [5/40 (12.5%) vs. 1/42 (2.4%), P = 0.04] were more likely to develop decompensated liver cirrhosis. On multivariate analysis, initial fibrosis stage F2 or F3 was independently associated with progression to decompensated liver cirrhosis (relative risk 2.3, 95% confidence interval 0.03-2.5, P = 0.02). CONCLUSION: Chinese chronic hepatitis C virus patients with persistently normal alanine aminotransaminase levels with moderate to severe fibrosis at initial evaluation are more likely to develop decompensated liver cirrhosis.

In vitro genetic transfer of protein synthesis and respiration defects to mitochondrial DNA-less cells with myopathy-patient mitochondria.

A severe mitochondrial protein synthesis defect in myoblasts from a patient with mitochondrial myopathy was transferred with myoblast mitochondria into two genetically unrelated mitochondrial DNA (mtDNA)-less human cell lines, pointing to an mtDNA alteration as being responsible and sufficient for causing the disease. The transfer of the defect correlated with marked deficiencies in respiration and cytochrome c oxidase activity of the transformants and the presence in their mitochondria of mtDNA carrying a tRNA(Lys) mutation. Furthermore, apparently complete segregation of the defective genotype and phenotype was observed in the transformants derived from the heterogeneous proband myoblast population, suggesting that the mtDNA heteroplasmy in this population was to a large extent intercellular. The present work thus establishes a direct link between mtDNA alteration and a biochemical defect.

Interpositional arthroplasty using autogenous costal cartilage graft for temporomandibular joint ankylosis in adults.

This retrospective study evaluated 11 adult patients with TMJ ankylosis treated by interpositional arthroplasty using autogenous costal cartilage grafts between 1985 and 2003. Minimum follow-up was 2 years. Basic personal data, function of TMJ and complications of operation were recorded. Mouth opening increased during operation by a mean of 25.5mm and postoperatively by a mean of 26.2mm. The procedure failed in one case with recurrent ankylosis. The remaining 10 cases had final opening ranges in excess of 30mm. Complications included one numb lower lip. There were no instances of a facial nerve or internal maxillary artery injury. Consideration is given to the width and level of gap arthroplasty, fixation of the grafts, complications at both donor and recipient sites, postoperative physical therapy, occlusal change, and the need for coronoidectomy. This study demonstrated that autogenous costal cartilage is a suitable material for interpositional arthroplasty in adults. Complications were low. The intraoral approach and the role of postoperative physical therapy appear key elements in the success of this procedure.

48 weeks pegylated interferon alpha-2a is superior to 24 weeks of pegylated interferon alpha-2b in achieving hepatitis B e antigen seroconversion in chronic hepatitis B infection.

BACKGROUND/AIM: Although 48-week therapy with pegylated-interferons has been shown to be effective for the treatment of chronic hepatitis B virus infection, the efficacy of a shorter duration of therapy with pegylated interferons is unknown. METHOD: We reviewed 53 hepatitis B e antigen positive Chinese patients treated with 48 weeks of pegylated interferon alpha-2a or 24 weeks of pegylated interferon alpha-2b. Sustained virological response was defined as hepatitis B e antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL at week 72. RESULTS: Twenty-nine patients were treated with 48 weeks of pegylated-interferon-alpha-2a and 24 patients with 24 weeks of pegylated-interferon-alpha-2b. At the end-of-therapy, hepatitis B e antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL were similar between the two groups of patients [9/29 (31.0%) vs. 2/24 (8.3%), respectively, P = 0.09]. At week 72, 10 of the 29 patients (34.5%) treated with 48 weeks of pegylated-interferon-alpha-2a compared with two of the 24 patients (8.3%) treated with 24 weeks of pegylated-interferon-alpha-2b had sustained virological response (P = 0.04). By logistic analysis, 48 weeks of pegylated-interferon-alpha-2a was independently associated with sustained virological response (P = 0.04 adjusted hazards-ratio 9.37). CONCLUSION: Further studies are required to determine the optimal duration of therapy with pegylated interferons in chronic hepatitis B.

Skin whitening capability of shikimic acid pathway compound.

OBJECTIVE: To examine the skin whitening capabilities of shikimic acid pathway compounds and find the most effective molecule to be used as the active ingredient for skin whitening products. MATERIALS AND METHODS: Skin whitening is the practice of using chemical substances to lighten skin tone by the lessening the concentration of melanin. The whitening efficacy of shikimic acid pathway compounds was evaluated. Eight compounds in the shikimic acid pathway were chosen for this study: benzoic acid, p-coumaric acid, vanillic acid, syringic acid, quinic acid, shikimic acid, orcinol monohydrate, and phenyl pyruvic acid. We measured the tyrosinase inhibitory capacity of the compounds in the animal model of zebrafish and also evaluated the compounds' anti-oxidant activities using the DPPH radical scavenging, and ABTS+ free radical scavenging tests. Compounds' cytotoxicity effects were also evaluated. RESULTS: Amongst eight shikimic acid pathway compounds used in this study, shikimic acid was the most potent tyrosinase-inhibitor and the most efficient compound to be used as an active ingredient for skin whitening. Shikimic acid revealed a good radical scavenging activity (RAS) with low cell toxicity. CONCLUSIONS: Promising results obtained in this study may open a new window of opportunity to introduce another compound to be used in the skin-whiting cosmetics industry.

Re-emergence of fatal human influenza A subtype H5N1 disease.

Human disease associated with influenza A subtype H5N1 re-emerged in January, 2003, for the first time since an outbreak in Hong Kong in 1997. Patients with H5N1 disease had unusually high serum concentrations of chemokines (eg, interferon induced protein-10 [IP-10] and monokine induced by interferon gamma [MIG]). Taken together with a previous report that H5N1 influenza viruses induce large amounts of proinflammatory cytokines from macrophage cultures in vitro, our findings suggest that cytokine dysfunction contributes to the pathogenesis of H5N1 disease. Development of vaccines against influenza A (H5N1) virus should be made a priority.

Absence of association between angiotensin converting enzyme polymorphism and development of adult respiratory distress syndrome in patients with severe acute respiratory syndrome: a case control study.

BACKGROUND: It has been postulated that genetic predisposition may influence the susceptibility to SARS-coronavirus infection and disease outcomes. A recent study has suggested that the deletion allele (D allele) of the angiotensin converting enzyme (ACE) gene is associated with hypoxemia in SARS patients. Moreover, the ACE D allele has been shown to be more prevalent in patients suffering from adult respiratory distress syndrome (ARDS) in a previous study. Thus, we have investigated the association between ACE insertion/deletion (I/D) polymorphism and the progression to ARDS or requirement of intensive care in SARS patients. METHOD: One hundred and forty genetically unrelated Chinese SARS patients and 326 healthy volunteers were recruited. The ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis. RESULTS: There is no significant difference in the genotypic distributions and the allelic frequencies of the ACE I/D polymorphism between the SARS patients and the healthy control subjects. Moreover, there is also no evidence that ACE I/D polymorphism is associated with the progression to ARDS or the requirement of intensive care in the SARS patients. In multivariate logistic analysis, age is the only factor associated with the development of ARDS while age and male sex are independent factors associated with the requirement of intensive care. CONCLUSION: The ACE I/D polymorphism is not directly related to increased susceptibility to SARS-coronavirus infection and is not associated with poor outcomes after SARS-coronavirus infection.

Clopidogrel-induced hepatotoxicity after percutaneous coronary stenting.

Clopidogrel, an adenosine diphosphate receptor blocker, is widely used as an adjunctive antiplatelet therapy in acute coronary syndrome and percutaneous coronary stenting. The occurrence of hepatotoxicity is rare. We describe the occurrence of symptomatic liver disease in a 74-year-old man 5 weeks following commencement of therapy with clopidogrel. The reported cases of clopidogrel-induced hepatotoxicity are reviewed and the clinical significance of this event are discussed.

Sequential changes in heart rate variability after coronary artery bypass grafting.

Heart rate variability (HRV) decreased soon after coronary artery bypass grafting and returned to the preoperative level within 2 months; however, HRV did not exceed the preoperative level, even 6 months after coronary artery bypass grafting. Although myocardial ischemia can be improved by coronary artery bypass grafting, HRV did not benefit from coronary artery bypass grafting within 6 months.

Lamivudine treatment for fulminant hepatic failure due to acute exacerbation of chronic hepatitis B infection.

BACKGROUND: Exacerbation of chronic hepatitis B infection can lead to fulminant hepatic failure with a mortality of up to 90%. AIM: To evaluate the efficacy of lamivudine in the treatment of this subgroup of patients. METHODS: Twenty-four patients with exacerbation of chronic hepatitis B infection and fulminant hepatic failure were treated with lamivudine, 100 mg daily. Hepatitis A, C, D and human immunodeficiency virus co-infections and hepatocellular carcinoma were excluded. RESULTS: The median age was 53 years (range, 24-77 years) with a male predominance of 20:4. Seventeen patients were hepatitis B e antigen positive. Mean hepatitis B virus DNA was 2079 Meq/mL. Eight patients (33%) survived (group A). Thirteen patients died and three patients received liver transplantation (67%) (group B). Baseline laboratory results were comparable between the two groups, including serum albumin, bilirubin, alanine aminotransferase, prothrombin time and creatinine. Group B patients had significantly more comorbid illnesses at baseline and more complications, including sepsis and renal failure, compared with group A patients. Six out of eight survivors (75%) had full hepatitis B e antigen seroconversion, but this was not sustained in four patients. CONCLUSIONS: Lamivudine may be useful in treating patients with fulminant hepatic failure due to exacerbation of chronic hepatitis B. Hepatitis B e antigen seroconversion was less durable in this subgroup of patients and long-term therapy may be required.

Postoperative deep vein thrombosis in the Taiwanese Chinese population.

Reports of the incidence of postoperative deep vein thrombosis in the Chinese population of Taiwan are few in the literature. Over a 3 year period, the fibrinogen degradation products test, the pulse volume recorder, and venography were used to study 220 patients undergoing major operations at the Veterans General Hospital in Taipei, Taiwan. Deep vein thrombosis was found in 17 patients (7.7 percent). A comparison of the three diagnostic methods showed that the sensitivities of the fibrinogen degradation products test and the pulse volume recorder were 56.3 percent and 93.7 percent, respectively; the specificities, 97.4 percent and 95.7 percent, respectively; and the accuracies, 85.5 percent and 95.5 percent, respectively. These results support the combined use of the fibrinogen degradation products test and the pulse volume recorder for screening and diagnosing deep vein thrombosis.

Association of self-limited cytomegalovirus colitis and shigellosis in an immunocompetent patient.

Cytomegalovirus (CMV) infection of the colon has been rarely reported in immunocompetent patients. Patients with severe acute illness or disseminated CMV infection have high mortality. In contrast, the patients with local injury of the colon due either to other gastrointestinal infections or to anal intercourse, who are otherwise healthy, usually have self-limited disease. The CMV infection is believed to be the bystander and may be treated conservatively. Concomitant CMV colitis and other gastrointestinal infections occur exclusively in immunosuppressed patients. We report, to our knowledge, the first case of co-infection of the colon with CMV and Shigella in an immunocompetent patient. The hypothesis is that the mucosal damage caused by Shigella infection may predispose the colon to secondary CMV invasion.

Risk factors for mortality in primary isolated coronary artery bypass grafting surgery.

BACKGROUND AND PURPOSE: Identifying the risk factors for mortality in coronary artery bypass grafting (CABG) surgery is important to improve surgical results. The purpose of this study was to identify the risk factors for mortality in primary isolated CABG in a series of Taiwanese patients. METHODS: Medical records of 914 patients who underwent primary isolated CABG surgery in Veterans General Hospital-Taipei during the period from January 1, 1991, to December 31, 1995, were reviewed. Eighteen clinical and seven operative variables were included in the univariate and multivariate analyses to identify the determinants of mortality in CABG surgery. RESULTS: Thirty-one patients (3.4%) died within 30 days after surgery; 41 (4.5%) died during hospitalization for the procedure. After univariate and multivariate analyses, emergency surgery, history of myocardial infarction, concomitant peripheral artery occlusive disease (PAOD), and prolonged cardiopulmonary bypass (CPB) were found to be significant determinants of mortality in primary isolated CABG. Other variables, including age, sex, angina class, NYHA class, diabetes mellitus, the number of anastomoses, aortic cross-clamp time, stenosis of the left main coronary artery, the number of stenotic coronary arteries, history of congestive heart failure, and a left ventricular ejection fraction less than 35%, were not significant determinants of mortality. Patients undergoing emergency surgery were found to be at highest risk of mortality. CONCLUSIONS: Patients undergoing emergency surgery who had a history of myocardial infarction, concomitant PAOD, or prolonged CPB were at higher risk of mortality in CABG surgery. More comprehensive techniques in myocardial protection, surgical procedures, and postoperative care should be used in the treatment of high-risk patients to reduce mortality.

Effect of magnolol on coronary vascular resistance in rabbits: measurement with pulsed Doppler velocimetry.

BACKGROUND AND PURPOSE: Magnolol is an active component purified from Magnolia officinalis that has been reported to protect the myocardium against infarction and reperfusion injury. The purpose of this study was to investigate the effect of magnolol on the coronary circulation and to determine whether a change in coronary vascular resistance could be the mechanism underlying its myocardial protective effect. METHODS: Male New Zealand white rabbits were anesthetized. A 3-mm suction-type pulsed Doppler velocimetry probe was applied to the proximal part of the left anterior descending coronary artery after median sternotomy. The 39 rabbits received intravenous injection of either vehicle (n = 5), magnolol (10(-6) g/kg, n = 6; 10(-5) g/kg, n = 5; 10(-4) g/kg, n = 5), or nitroglycerin (10(-5) g/kg, n = 6; 10(-4) g/kg, n = 6; 10(-3) g/kg, n = 6). The effects of magnolol and nitroglycerin on coronary vascular resistance were compared. RESULTS: Magnolol did not change blood pressure or coronary blood flow velocity. However, at a dose of 10(-4) g/kg, it decreased coronary vascular resistance significantly more than vehicle (88 +/- 1% vs 95 +/- 1% of baseline coronary vascular resistance, p < 0.001). Nitroglycerin increased coronary blood flow velocity and decreased coronary vascular resistance in a dose-dependent manner (p < 0.01). CONCLUSIONS: Magnolol reduced coronary vascular resistance in anesthetized, open-chest rabbits only at a high concentration. Its effect was modest compared with that of nitroglycerin. Since magnolol protects the myocardium at relatively low doses, coronary vasodilatation is unlikely to be the underlying mechanism responsible for its myocardial protective effects.

Effects of dipyridamole, nitroglycerin, and nitroprusside on coronary vascular resistance in rabbits: measurement with pulsed Doppler velocimetry.

Dipyridamole, nitroglycerin, and nitroprusside are all effective vasodilators. However, few studies have compared their in vivo coronary vasodilatation effects. The purpose of this study was to compare the effects of these agents on coronary blood flow velocity and vascular resistance in anesthetized, open-chest rabbits. Male New Zealand white rabbits were anesthetized, and a 3-mm, suction-type, pulsed Doppler velocimeter probe was applied to the proximal part of the left anterior descending coronary artery after median sternotomy. The rabbits received infusion of various doses of dipyridamole (0.1 mg/kg, n = 5; 1 mg/kg, n = 5; 10 mg/kg, n = 9), nitroglycerin (0.01 mg/kg, n = 8; 0.1 mg/kg, n = 5; 1 mg/kg, n = 5; 10 mg/kg, n = 7), or nitroprusside (0.01 mg/kg, n = 5; 0.1 mg/kg, n = 5; 1 mg/kg, n = 5). The percent changes in coronary blood flow velocity and coronary vascular resistance were measured. All three vasodilators increased coronary blood flow velocity significantly and decreased coronary vascular resistance dose-dependently. The dose-response curves of dipyridamole, nitroglycerin, and nitroprusside were significantly different from one another (p < 0.01). Dipyridamole at a dose of 10 mg/kg produced the greatest increase in coronary blood flow velocity and the greatest reduction in coronary vascular resistance in anesthetized, open-chest rabbits.