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Biomedical subjects

A C Chan

Publications and source records attributed to A C Chan.

At least 73 records · Page 4Linked to original sources

ERCP and pyogenic liver abscess.

BACKGROUND: Liver abscess is commonly biliary in origin. We assessed the role of endoscopic retrograde cholangiopancreatography (ERCP) in patients with pyogenic liver abscesses. METHODS: Between January 1986 and December 1997, 63 patients with pyogenic liver abscesses were referred for ERCP. Twenty-one patients had a history of previous biliary procedures including cholecystectomy (21), biliary-enteric bypass (9), surgical sphincteroplasty (5), and endoscopic sphincterotomy (2). Demographic data, clinical features, biochemical parameters, treatment, clinical progress, and follow-up were recorded and analyzed. RESULTS: Two patients required laparotomy and 61 patients underwent guided aspiration and/or drainage at a median interval of 3 days after presentation. ERCP was performed at a median of 8 days (range 1 to 69 days) after initial treatment and succeeded in 90% of cases with no associated complication or death. Abnormalities were shown in 29 (46%) patients: biliary obstruction due to stones or strictures (15), ductal dilatation alone (7), spontaneous choledochoduodenal fistula (3), communication between abscesses and biliary tree (3), and splaying of biliary ducts by space-occupying effect (2). No abnormality was found in 34 patients. Eight patients underwent endoscopic therapy including sphincterotomy (5), stone extraction (6), and nasobiliary drainage (2). Overall mortality rate from liver abscesses was 6%. CONCLUSIONS: ERCP is useful in the treatment of patients with pyogenic liver abscesses.

Adolescent↗

New wire-guided basket for intrahepatic stone extraction.

BACKGROUND: Endoscopic extraction of intrahepatic ductal stones with conventional stone retrieval baskets sometimes is difficult when the stones are deep in the segmental ducts or in a tortuous duct. We evaluated the use of a new wire-guided basket for endoscopic bile duct stone extraction. METHODS: The new wire-guided basket has a separate lumen for the guidewire on one side of the catheter. It is rail-loaded and advanced over a guidewire into the desired segmental duct. After they are engaged, the stones are dragged into the duodenum and the guidewire is left in the segmental duct. The basket then can be reinserted into that particular ductal segment over the wire for further stone extraction. RESULTS: The basket was used to treat three patients. Two patients had multiple intrahepatic stones. Repeated passage of the basket back to the desired location was accomplished without difficulty. All stones were removed successfully. CONCLUSION: The new wire-guided basket is a useful device for removing intrahepatic stones, particularly from patients with multiple ductal stones.

Bile Duct Diseases↗

Meta-analysis of antibiotic prophylaxis in endoscopic retrograde cholangiopancreatography (ERCP).

BACKGROUND AND STUDY AIMS: Considerable controversy exists regarding the role of antibiotic prophylaxis prior to endoscopic retrograde cholangiopancreatography (ERCP), in that various studies of antibiotic prophylaxis have reached conflicting conclusions. The aim of this meta-analysis is to synthesize the data in order to determine whether antibiotic prophylaxis reduces the rate of occurrence of bacteremia and/or the rate of sepsis/cholangitis among patients undergoing ERCP. PATIENTS AND METHODS: Clinical trials were selected via Medline and Pubmed using subject words and textwords "ERCP", "antibiotic" and "antibiotic prophylaxis". Summary estimates of the risk ratios for the outcomes of bacteremia and sepsis/cholangitis were calculated. RESULTS: After 49 abstracts had been reviewed, seven randomized placebo-controlled trials of antibiotic prophylaxis prior to ERCP were identified. Upon further review, two studies were excluded because patients received antibiotics before and after the ERCP. Four studies reported on the clinical outcome of bacteremia. Five studies reported on the clinical outcome of sepsis/cholangitis. The summary relative risk of the association between antibiotic prophylaxis and bacteremia was 0.39 (95% CI, 0.12-1.29). For sepsis/cholangitis the summary relative risk was 0.91 (95 % CI, 0.39-2.15). CONCLUSIONS: Antibiotic prophylaxis prior to ERCP may reduce the incidence of bacteremia but this has little clinical relevance. Prophylaxis does not substantially reduce the incidence of sepsis/cholangitis and thus the routine use of antibiotic prophylaxis cannot be recommended.

Antibiotic Prophylaxis↗

Small-bowel perforations related to endoscopic retrograde cholangiopancreatography (ERCP) in patients with Billroth II gastrectomy.

BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is one of the mainstays in the diagnosis and treatment of hepatobiliary and pancreatic diseases, and is also increasingly used for patients with previous Billroth II gastrectomy. The aim of this study was to review our experience of ERCP in patients with Billroth II gastrectomy, and the complications associated with this procedure. PATIENTS AND METHODS: The records of 110 patients with Billroth II gastrectomy, treated between January 1993 and December 1997, were received retrospectively. Details noted included indications for ERCP, therapeutic interventions, causes of failure, and complications. RESULTS: A total of 110 patients underwent ERCP; the total number of ERCP attempts was 185. The major indications for ERCP were cholangitis (31%), common bile duct stones (22%), and jaundice (15%). The endoscope was successfully passed up to the papilla in 134 examinations (71%), and selective cannulation was successful in 122 of these (66%). There were 63 (34%) failed ERCP attempts. Causes of failure were: difficulty in entering the afferent loop (n = 19, 10%), failure to enter the duodenum (n = 23, 12%), endoscope-related bowel perforation (n = 9, 5%), and failed cannulation (n = 10, 6%). The other two failures were caused by desaturation in the patient, and inability to distend the duodenum. The major complication of the procedure was perforation, which occurred in 11 examinations (6%). Of these perforations, nine occurred in the small bowel while the endoscope was being manipulated through the afferent loop; these patients required laparotomy. Two patients had retroduodenal perforations, one occurring after sphincterotomy and one after cannulation. Both patients were successfully managed conservatively. Three patients suffered bleeding after sphincterotomy (3/185 procedures, 1.6%), and one patient developed acute pancreatitis. These were managed conservatively. The overall complication rate was 8%. There were two deaths among the patients with small-bowel perforations, and consequently an overall mortality rate of 1% (2/185 procedures). CONCLUSIONS: Most complications of ERCP in patients with previous Billroth II gastrectomy were caused by bowel perforation while the endoscope was being manipulated through the afferent limb. Such perforations are intraperitoneal and require surgical intervention.

Adult↗

Interaction of antioxidants and their implication in genetic anemia.

The generation of reactive oxygen species (ROS) is a steady-state cellular event in respiring cells. Their production can be grossly amplified in response to a variety of pathophysiological conditions such as inflammation, immunologic disorders, hypoxia, hyperoxia, metabolism of drug or alcohol, exposure to UV or therapeutic radiation, and deficiency in antioxidant vitamins. Uncontrolled production of ROS often leads to damage of cellular macromolecules (DNA, protein, and lipids) and other small antioxidant molecules. A number of major cellular defense mechanisms exist to neutralize and combat the damaging effects of these reactive substances. The enzymic system functions by direct or sequential removal of ROS (superoxide dismutase, catalase, and glutathione peroxidase), thereby terminating their activities. Metal binding proteins, targeted to bind iron and copper ions, ensure that these Fenton metals are cryptic. Nonenzymic defense consists of scavenging molecules that are endogenously produced (GSH, ubiquinols, uric acid) or those derived from the diet (vitamins C and E, lipoic acid, selenium, riboflavin, zinc, and the carotenoids). These antioxidant nutrients occupy distinct cellular compartments and among them, there are active recycling. For example, oxidized vitamin E (tocopheroxy radical) has been shown to be regenerated by ascorbate, GSH, lipoic acid, or ubiquinols. GSH disulfides (GSSG) can be regenerated by GSSG reductase (a riboflavin-dependent protein), and enzymic pathways have been identified for the recycling of ascorbate radical and dehydroascorbate. The electrons that are used to fuel these recycling reactions (NADH and NADPH) are ultimately derived from the oxidation of foods. Sickle cell anemia, thalassemia, and glucose-6-phosphate-dehydrogenase deficiency are all hereditary disorders with higher potential for oxidative damage due to chronic redox imbalance in red cells that often results in clinical manifestation of mild to serve hemolysis in patients with these disorders. The release of hemoglobin during hemolysis and the subsequent therapeutic transfusion in some cases lead to systemic iron overloading that further potentiates the generation of ROS. Antioxidant status in anemia will be examined, and the potential application of antioxidant treatment as an adjunct therapy under these conditions will be discussed.

Anemia↗

Assessing chemotherapy response of squamous cell oesophageal carcinoma with spiral CT.

45 patients with squamous cell carcinoma of the oesophagus were examined prior to, and following, pre-operative chemotherapy by spiral CT. Oesophageal CT was performed following gaseous distention of the oesophagus. TNM stage and perceived resectability on CT before and after chemotherapy were compared and related to surgical resectability and pathological staging. T-stage changed in 26% and N-stage changed in 9% of tumours after chemotherapy. Post-chemotherapy CT predicted pathological T-stage with an accuracy of 88% and N-stage with an accuracy of 84%. Six of 14 tumours considered irresectable on CT pre-chemotherapy were considered resectable on post-chemotherapy CT. Five of these six tumours were resectable at surgery. Post-chemotherapy CT predicted surgical resectability with an accuracy of 88%, the main pitfall being underestimation and overestimation of tracheobronchial invasion. CT prediction of chemotherapy response as judged by change in tumour volume was compared with a quantitative pathological assessment of chemotherapy response. 93% of oesophageal tumours changed volume after chemotherapy with 51% having a volume reduction of > or = 50%. However, no correlation was found between tumour volume reduction on serial CT examinations and either a quantitative pathological assessment of tumour response or patient survival.

Carcinoma, Squamous Cell↗

Sex, competitiveness, and intimacy in same-sex friendship in Hong Kong adolescents.

One of the alleged reasons that males report lower intimacy in same-sex friendships than females is that males tend to be more competitive than females, but this assumption has not been empirically tested. In the current study, 121 Hong Kong adolescents filled out Chinese versions of the Intimate Friendship Scale and the Competitiveness Index. As predicted, females reported having more intimate same-sex relationships than males, and they scored lower on competitiveness than males. However, the correlations between scores on the Competitiveness Index and the Intimate Friendship subscales were small and nonsignificant, suggesting that the sex difference in intimacy was not a function of competitiveness.

Adolescent↗

Structural basis for Syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory SH2 domains bound to a dually phosphorylated ITAM peptide.

The Syk family of kinases, consisting of ZAP-70 and Syk, play essential roles in a variety of immune and non-immune cells. This family of kinases is characterized by the presence of two adjacent SH2 domains which mediate their localization to the membrane through receptor encoded tyrosine phosphorylated motifs. While these two kinases share many structural and functional features, the more ubiquitous nature of Syk has suggested that this kinase may accommodate a greater variety of motifs to mediate its function. We present the crystal structure of the tandem SH2 domain of Syk complexed with a dually phosphorylated ITAM peptide. The structure was solved by multiple isomorphous replacement at 3.0 A resolution. The asymmetric unit comprises six copies of the liganded protein, revealing a surprising flexibility in the relative orientation of the two SH2 domains. The C-terminal phosphotyrosine-binding site is very different from the equivalent region of ZAP-70, suggesting that in contrast to ZAP-70, the two SH2 domains of Syk can function as independent units. The conformational flexibility and structural independence of the SH2 modules of Syk likely provides the molecular basis for the more ubiquitous involvement of Syk in a variety of signal transduction pathways.

Amino Acid Sequence↗

No evidence of replication error phenotype in primary gastric lymphoma of mucosa-associated lymphoid tissue.

Replication error (RER) phenotype, caused by deficiency of DNA mismatch repair genes and revealed by widespread microsatellite instability, has been detected in subsets of a wide variety of solid tumors, but rarely in lymphomas in general. So far, the involvement of RER phenotype in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) type has not been conclusively established. We therefore examined 9 microsatellite loci on 5 chromosomes [D2S123, D3S11, D3S1261, D3S1262, D3S1265, D6S262, D18S559, a CTTT(T) repeat in intron 20 of RBI gene and a CA repeat in p53 locus] in 33 cases of primary gastric MALT lymphoma for evidence of microsatellite instability by polymerase chain reaction using primers end-labeled with [gamma-33P] ATP. Although novel-length allele was observed in 7 of 33 cases (21.2%), none of these 7 cases showed changes in more than one locus. RER phenotype was scored as positive in a case when more than 1 of the 9 examined microsatellite loci showed length alterations. Accordingly, none of the 33 cases had a RER phenotype. This result suggests that the pathogenesis of gastric MALT lymphoma does not involve RER phenotype. It is consistent with the general observations in lymphomas, but is highly in contrast to a previous report showing more than 50% of MALT lymphomas with the RER phenotype.

DNA Ligases↗

Mutation of the 5' noncoding region of the BCL-6 gene in low-grade gastric lymphoma of the mucosa-associated lymphoid tissue.

BCL-6 gene rearrangement and hypermutations were investigated in four Hong Kong Chinese patients with low-grade gastric lymphoma of the mucosa-associated lymphoid tissue (MALToma). The former was studied by Southern analysis and the latter by the technique of polymerase chain reaction and denaturing gradient gel electrophoresis. BCL-6 gene rearrangement was not detectable in any of the four cases. However, mutations at both the E1.11 and E1.12 segments of the 5' noncoding region of the BCL-6 gene were found in two patients. This preliminary observation suggests that the mutations of the 5' noncoding region of the BCL-6 gene rather than gene rearrangement may be playing a more important role in the tumorigenesis of low-grade gastric MALToma. Further confirmation of this finding by studying a larger number of patients will be required.

Aged↗

Near tetraploidy in three cases of acute myeloid leukemia associated with mediastinal granulocytic sarcoma.

Granulocytic sarcoma (GS) is a rare manifestation of acute myeloid leukemia (AML), blastic transformation of chronic myeloid leukemia, and the myelodysplastic syndromes. The mediastinum is an unusual site of presentation. We report a series of three female patients with mediastinal GS. They were characterized by the presence of large and bizarre blast cells and near tetraploidy on cytogenetic analysis. All three patients responded poorly to chemotherapy. Near tetraploid AML is a rare entity, usually present in male patients, and has not been associated with GS. The clinical and pathological similarities in these three cases suggest a distinct category of poor-risk AML for which more intensive treatment is needed.

Adult↗

Lysophosphatidylcholine stimulates the release of arachidonic acid in human endothelial cells.

Lysophosphatidylcholine (lyso-PC) is a product of phosphatidylcholine hydrolysis by phospholipase A2 (PLA2) and is present in cell membranes, oxidized lipoproteins, and atherosclerotic tissues. It has the ability to alter endothelial functions and is regarded as a causal agent in atherogenesis. In this study, the modulation of arachidonate release by lyso-PC in human umbilical vein endothelial cells was examined. Incubation of endothelial cells with lyso-PC resulted in an enhanced release of arachidonate in a time- and concentration-dependent manner. Maximum arachidonate release was observed at 10 min of incubation with 50 microM lyso-PC. Lyso-PC species containing palmitoyl (C16:0) or stearoyl (C18:0) groups elicited the enhancement of arachidonate release, while other lysolipids such as lysophosphatidylethanolamine, lysophosphatidylserine, lysophosphatidylinositol, or lysophosphatidate were relatively ineffective. Lyso-PC-induced arachidonate release was decreased by treatment of cells with PLA2 inhibitors such as para-bromophenacyl bromide and arachidonoyl trifluoromethyl ketone. Furthermore, arachidonate release was attenuated in cells grown in the presence of antisense oligodeoxynucleotides that specifically bind cytosolic PLA2 mRNA. Treatment of cells with lyso-PC resulted in a translocation of PLA2 activity from the cytosolic to the membrane fractions of cells. Lyso-PC induced a rapid influx of Ca2+ from the medium into the cells, with a simultaneous enhancement of protein kinase C (PKC) activity in the membrane fractions. The lyso-PC-induced arachidonate release was attenuated when cells were preincubated with specific inhibitors of PKC (staurosporine and Ro31-8220) or a specific inhibitor of mitogen-activated protein kinase/extracellular regulated kinase kinase (PD098059). Taken together, the results of this study show that lyso-PC caused the elevation of cellular Ca2+ and the activation of PKC, which stimulated cytosolic PLA2 in an indirect manner and resulted in an enhanced release of arachidonate.

Arachidonic Acid↗

Helicobacter pylori and the null genotype of glutathione-S-transferase-mu in patients with gastric adenocarcinoma.

BACKGROUND: Chronic Helicobacter pylori infection now is recognized as an important causative agent for gastric carcinoma. However, only a small minority of infected individuals develop the malignancy, even in areas with a high prevalence of gastric carcinoma. It has been postulated that the absence of glutathione-S-transferase-mu (GST-mu), which impairs detoxification of exogenous carcinogens, might predispose some infected individuals to the development of gastric carcinoma. METHODS: Patients with histologically confirmed adenocarcinoma of the stomach were tested for H. pylori infection and the GST-mu genotype. Prevalence of GST-mu gene deletion was compared with the H. pylori status of the patients. A group of gender- and age-matched control subjects with known H. pylori-related nonulcer dyspepsia also were tested for the GST-mu genotype and compared with patients with H. pylori positive carcinoma. RESULTS: Fifty-one patients with gastric adenocarcinoma were enrolled into the study. Thirty-five were found to have H. pylori in the resected specimens. The null genotype of GST-mu was significantly more common among those patients with H. pylori positive carcinoma compared with the H. pylori negative group (65.7% vs. 31.3%; P < 0.05). Homozygous deletion of GST-mu was significantly higher in the H. pylori positive carcinoma patients than in the H. pylori-infected, nonmalignant control group (65.7% vs. 37.1%; P < 0.05). CONCLUSIONS: The null genotype for GST-mu is found more commonly in gastric carcinoma associated with H. pylori infection. The absence of the GST-mu enzyme may increase the risk of the development of gastric carcinoma in these patients.

Adenocarcinoma↗

Mantle cell lymphoma in the Chinese: clinicopathological features and treatment outcome.

We report the clinical, molecular, and immunohistological findings of 20 Chinese patients with mantle cell lymphoma diagnosed over a 10-year period. The disease affected mainly elderly patients (median age, 65.5 years) with a male predominance (M/F, 3/1). Eighty percent presented with advanced stage III/IV disease but only 25% had B symptoms. Eighty-five percent had extranodal disease at presentation. Complete remission (CR) and partial remission (PR) were achieved in 45% and 40% of the patients, respectively. There was no difference in the CR rate for patients treated with anthracycline-containing or nonanthracycline-containing regimens (43% and 50%, P = 0.67). Disease progression or relapse was observed after a median of 26 months in patients who initially responded to treatment. Extranodal relapse occurred in the central nervous system (n = 1), bone marrow (n = 1), pleura (n = 2), orbit (n = 2), and the gastrointestinal tract (n = 3). The median overall survival (OS) was 52 months but there were no long-term survivors. This was not different from the median OS of 53 months of patients with diffuse large cell (DLC) lymphoma treated in the same center over the same period (log rank, P = 0.76). Of the 12 patients who were tested for bcl-1 rearrangement by polymerase chain reaction (PCR), five (42%) were positive for rearrangement in the major translocation cluster (MTC) region. The median OS rates were 45 months and 63 months for PCR positive and negative patients, respectively (P = 0.97). In conclusion, MCL is a disease mainly of the elderly in the Chinese with a male predominance and most had advanced-stage disease and extranodal involvement at presentation. Clinicopathologic features and treatment outcome were similar to Caucasian patients, in that the disease combined the aggressive nature of DLC lymphoma and the incurability of low-grade lymphoma.

Aged↗

Epstein-Barr virus infection and its gene expression in gastric lymphoma of mucosa-associated lymphoid tissue.

The role of Epstein-Barr virus (EBV) in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) has not been well understood. The aim of the study was to investigate EBV infection and its gene expression in this tumor in order to understand its role in the pathogenesis. EBV infection was screened by in situ hybridization for EBV-encoded non-polyadenylated RNA (EBER ISH) in 79 cases of gastric MALT lymphoma of nonimmunocompromised patients. The expression of EBV proteins [LMP1 (latent membrane protein 1), EBNA2 (EBV nuclear antigen 2), ZEBRA (switch protein encoded by BZLF1 gene)] was studied by immunohistochemistry in EBER-positive cases. EBV was detected with EBER ISH in 15 (19%) of the 79 cases. EBV was found in virtually all tumor cells in 2 cases of high-grade MALT lymphoma (2.5%) (EBV-associated), and was found only in occasional large or small lymphoid cells in 13 cases (16.5%). False positive EBER signal was detected in the mucinous glandular epithelial cells of gastric antrum with FITC-labeled oligonucleotide probe but not with digoxigenin or 35S-labeled riboprobes. Type II latency (EBER+LMP1+ EBNA2-) was detected in both EBV-associated cases. Type III latency (EBER+LMP1+EBNA2+) was also identified in one EBV-associated case besides latency II. Double labeling showed coexpression of LMP1 and EBNA2 in a small number of tumor cells, indicating the presence of type III latency in single cell level. In cases with only occasional EBER-positive large or small lymphoid cells, LMP1 and EBNA2 were not detected. ZEBRA was negative in all the cases. These findings suggest that EBV may contribute to the pathogenesis of a small proportion of high-grade MALT lymphoma, where virtually all tumor cells harbored EBV and the oncogenic viral protein LMP1 was expressed. Moreover, latency III of EBV infection may exist in nonimmunocompromised patient.

Animals↗

Frequent detection of Epstein-Barr virus-infected B cells in peripheral T-cell lymphomas.

Although Epstein-Barr virus (EBV) positivity has been described in peripheral T-cell lymphomas (PTCLs) in Chinese patients, the cellular lineage of EBV-harbouring cells is unknown. Forty-four cases of PTCL were therefore studied by in situ hybridization (ISH) for EBV-encoded small non-polyadenylated RNA 1 and 2 (EBER), and the lineage of the EBER+ cells was determined by double labelling. The findings were further correlated with the clonality of EBV and the genotype of these EBER+ tumours. The results for the detection of EBV by ISH show that 23 of the 44 cases were EBER+. In 5/23 of the EBER+ cases, EBER was found in around 50 per cent of atypical cells and in 18/23 cases, EBER was found in a subpopulation of atypical cells. Among the EBER+ cases, all 15 tested showed clonal T-cell receptor gene rearrangement by Southern blot hybridization. Double labelling was successfully done in 11 EBER+ cases, and by comparison, EBER+/CD20+ B cells outnumbered the EBER+/CD3+ T cells in all these cases. EBV clonality analysis revealed that EBV was monoclonal in six EBER+ cases and biclonal in three cases. With the predominance of EBV+ B cells over EBV+ neoplastic T cells being observed in most of these cases, it is possible that the EBV-infected clonal population may be of B-cell lineage. This was supported in some cases where a faint clonal band was seen over a background smear in the gene rearrangement study of immunoglobulin heavy chain gene by polymerase chain reaction (PCR), indicating a minor B-cell clone. It is concluded that in EBV+ PTCL, EBV is preferentially localized in B cells rather than neoplastic T cells. The neoplastic T cells may support the clonal proliferation of a subpopulation of EBV+ B cells in PTCLs.

B-Lymphocytes↗

Clinicopathological analysis of local spread of carcinoma of the tongue.

BACKGROUND: The aims of the study are three-dimensional analysis of mode and distance of local spread of oral tongue carcinoma. METHODS: The glossectomy specimens were examined in the coronal plane in 3 mm thickness section. RESULTS: There were 50 glossectomy specimens. The maximum spread was 1.8 cm. Ninety-six percent of specimens had local spread within 1.2 cm. The distance of spread was not correlated with tumor size, including the diameter, depth, and volume. The incidence of local recurrence was 27% with positive histological margin. Perineural infiltration was the most important prognostic factor for local recurrence and survival. CONCLUSIONS: A minimum of 1.5-cm surgical resection margin is recommended. A smaller margin is not recommended as it has significant risk of local recurrence. A maximum of 2-cm surgical resection margin is recommended; larger margins will increase the surgical morbidity without a significant advantage of local control.

Adolescent↗