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Biomedical subjects

E K Ng

Publications and source records attributed to E K Ng.

At least 19 recordsLinked to original sources

Characterization of a brain-specific nuclear LIM domain protein (FHL1B) which is an alternatively spliced variant of FHL1.

We have amplified and sequenced a novel, alternatively spliced variant of a human gene coding for the four-and-a-half LIM domain protein 1 (FHL1). This gene is located at chromosome Xq27 and the spliced variant is named FHL1B. The ORF of FHL1B cDNA codes for a LIM-only protein that possesses a zinc finger and three tandem repeats of LIM domains at the N-terminus with an active bipartite nuclear localization signal (NLS) motif and a possible RBP-J binding region at the C-terminus. FHL1B and FHL1 have the same N-terminal three-and-a-half LIM domains but different C-terminal protein sequences, due to the presence of an additional alternative exon 4b in FHL1B causing a frame-shift in the 3'coding region. RT-PCR results revealed that the expression of FHL1 is not restricted in skeletal muscle and heart, but is widely distributed in other tissues, including brain, placenta, lung, liver, kidney and pancreas, albeit as a low abundance transcript. In contrast, FHL1B is specifically expressed in brain. The C-terminal alternative region in FHL1B is sufficient to localize FHL1B in the nucleus of mammalian cell. FHL1B is probably related to neural differentiation and certain fragile X syndrome.

Alternative Splicing

Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcers.

BACKGROUND AND METHODS: After endoscopic treatment to control bleeding of peptic ulcers, bleeding recurs in 15 to 20 percent of patients. In a prospective, randomized study, we compared endoscopic retreatment with surgery after initial endoscopy. Over a 40-month period, 1169 of 3473 adults who were admitted to our hospital with bleeding peptic ulcers underwent endoscopy to reestablish hemostasis. Of 100 patients with recurrent bleeding, 7 patients with cancer and 1 patient with cardiac arrest were excluded from the study; 48 patients were randomly assigned to undergo immediate endoscopic retreatment and 44 were assigned to undergo surgery. The type of operation used was left to the surgeon. Bleeding was considered to have recurred in the event of any one of the following: vomiting of fresh blood, hypotension and melena, or a requirement for more than four units of blood in the 72-hour period after endoscopic treatment. RESULTS: Of the 48 patients who were assigned to endoscopic retreatment, 35 had long-term control of bleeding. Thirteen underwent salvage surgery, 11 because retreatment failed and 2 because of perforations resulting from thermocoagulation. Five patients in the endoscopy group died within 30 days, as compared with eight patients in the surgery group (P=0.37). Seven patients in the endoscopy group (including 6 who underwent salvage surgery) had complications, as compared with 16 in the surgery group (P=0.03). The duration of hospitalization, the need for hospitalization in the intensive care unit and the resultant duration of that stay, and the number of blood transfusions were similar in the two groups. In multivariate analysis, hypotension at randomization (P=0.01) and an ulcer size of at least 2 cm (P=0.03) were independent factors predictive of the failure of endoscopic retreatment. CONCLUSIONS: In patients with peptic ulcers and recurrent bleeding after initial endoscopic control of bleeding, endoscopic retreatment reduces the need for surgery without increasing the risk of death and is associated with fewer complications than is surgery.

Aged

Geographic distribution of vacA allelic types of Helicobacter pylori.

BACKGROUND & AIMS: Distinct allelic types of Helicobacter pylori vacA have been defined. The geographic distribution of vacA alleles and cagA was assessed in this study. METHODS: A total of 735 cultures from patients in 24 countries were analyzed by polymerase chain reaction and reverse hybridization on a line probe assay (LiPA). RESULTS: In 124 (16.9%) of the 735 cultures, multiple vacA genotypes were detected, permitting analysis of 611 strains. In Europe, a distribution gradient of s1 subtypes was observed. In northern and eastern Europe, 89% were subtype s1a. s1a and s1b were equally present in France and Italy, whereas in Spain and Portugal 89% of strains were subtype s1b. s1a and s1b were approximately equally prevalent in North America. In Central and South America, virtually all s1 strains were subtype s1b. Subtype s1c was observed in 77% of the s1 isolates from East Asia. m1 and m2a have equal presence, except on the Iberian peninsula and in Central and South America, where m1 (86.2%) is more prevalent than m2 (13.8%). Subtype m2b was found exclusively among East Asian s1c strains. In all parts of the world, vacA s1/cagA-positive genotypes were associated with peptic ulcer disease (P < 0.001). CONCLUSIONS: These data indicate a geographic distribution of H. pylori genotypes and aid in understanding the relationship of H. pylori with disease.

Alleles

A comparison study on physical properties of self-expandable esophageal metal stents.

BACKGROUND: Currently available esophageal expandable stents differ in design, material, and method of deployment. We compared the expansile force and the susceptibility to buckling force in five commercially available stents. METHODS: The Esophacoil, Wallstent, Ultraflex, Gianturco-Z and Song stents were tested. The middle sections of fully expanded stents were subjected to compression force using a universal tensile testing machine. The distortion of the stent was measured electronically and the expansile force was calculated. Bending moments were applied to the ends of the stents until buckling occurred in the inner parts. The buckling radius was measured as the radius of the inner curvature of the stent when this occurred. RESULTS: The stents tested were significantly different in their expansile forces and buckling radii. Song stent and Gianturco-Z stent were similar due to their similar designs. Esophacoil was the strongest with regard to withstanding compressive force and angulation force, followed by Wallstent. Ultraflex stent was the weakest in expansile force but withstood angulation force better than the Song and Gianturco stents. CONCLUSION: Esophageal stents differ greatly in their elasticity and resistance to angulation. Knowledge of their mechanical properties will be another helpful factor to consider in selecting the appropriate stent in addition to the geometry and consistency of the tumor.

Equipment Design

Evaluation of three commercial enzyme-linked immunosorbent assay kits for diagnosis of Helicobacter pylori in Chinese patients.

Most of the commercial serological assays for H. pylori are developed and validated in western countries. We evaluated the accuracy of three popular commercial ELISA tests for H. pylori in the Chinese population. Eighty dyspeptic patients were recruited and diagnosis of H. pylori infection was based on biopsy urease test, histology and urea breath test. Thirty-six patients (45%) were positive for H. pylori infection by two or more positive reference tests. Anti-H. pylori IgG antibody was detected by three commercial ELISA tests: GAP IgG (Bio-Rad), HM-CAP (Enteric Products) and Pyloriset EIA-G (Orion). The respective sensitivity, specificity, positive and negative predictive values of the three tests were: GAP IgG (50%, 97.4%, 93.8%, 71.7%), HM-CAP (72.7%, 68.4%, 66.7%, 74.3%) and Pyloriset EIA-G (75%, 86.4%, 81.8%, 80.9%). Despite the high accuracy reported in the West, the performance of these commercial serological tests was unsatisfactory when used in Chinese patients.

Adult

Total gastrectomy with extended lymphadenectomy for "curable" stomach cancer: experience in a non-Japanese Asian center.

BACKGROUND: Gastrectomy with extended lymphadenectomy is the advocated treatment in Japan for patients with "curable" stomach cancer. Attempts in units elsewhere adopting this approach failed to show any survival advantage, and the high operative mortality has prevented global acceptance of the operation. This study examines the safety and efficacy of radical gastrectomy in a Far East center outside Japan. STUDY DESIGN: A consecutive series of 121 patients with gastric cancer who fulfilled criteria for radical surgery had total gastrectomy with extended lymphadenectomy equivalent to D3 dissection over a 6-year period in a single unit. RESULTS: The operation carried a morbidity of 50%, with a perioperative mortality of 5%. Survival was best predicted by tumor stage: 5-year survival for patients with intact gastric serosa was 64%, versus 10% for those with serosal penetration (p < 0.001). The majority of documented metastases occurred by transperitoneal route in serosa-positive patients, but via the hematogenous mechanisms in those who were serosa-negative. CONCLUSIONS: Radical gastrectomy with extended lymphadenectomy carries high operative morbidity. Increased mortality occurred because of loco-regional recurrence in patients with T3/T4 diseases. Novel approaches including neoadjuvant treatment or regional therapy should be explored.

Adenocarcinoma

Prevalence and distribution of Helicobacter pylori in gastroesophageal reflux disease: a study from the East.

OBJECTIVES: The relationship between Helicobacter pylori infection and gastroesophageal reflux (H. pylori) disease (GERD) is controversial. In Asian populations, the prevalence of H. pylori infection is high and GERD is relatively uncommon. The aim of this study was 1) to test the hypothesis that H. pylori protects the esophagus against GERD, and 2) to study the pattern of H. pylori colonization and gastritis in GERD. METHODS: We conducted a prospective case-control study in which patients with GERD and asymptomatic controls were compared for the prevalence of H. pylori infection. Diagnosis of GERD was based on symptoms of heartburn that improved with acid-suppressive therapy and/or endoscopic evidence of erosive esophagitis. H. pylori status was determined by serology and, when endoscopy was indicated, was confirmed by rapid urease test and histology. Gastric biopsies were examined under hematoxylin and eosin and Giemsa stains. Density of H. pylori colonization and activity of gastritis at different parts of stomach were graded and compared according to Updated Sydney system. RESULTS: A total of 106 patients with GERD and 120 age- and sex-matched, asymptomatic controls were enrolled. The prevalence of H. pylori infection was significantly lower in GERD patients (31%) compared with controls (61%, p < 0.001, odds ratio 0.229, 95% confidence interval 0.13-0.41). H. pylori-infected GERD patients showed significantly more severe gastritis in the antrum than in other parts of stomach (mean inflammatory scores: antrum; 3.3 +/- 1.63*, body; 1.85 +/- 1.31; fundus; 1.65 +/- 0.58; cardia, 1.65 +/- 1.39; *p < 0.005). H. pylori colonization was found less commonly and at lower density at the cardia compared with other parts of the stomach. CONCLUSIONS: H. pylori infection protects against the development of GERD, and carditis is unlikely to play an important role.

Adult

Helicobacter pylori heat shock protein A: serologic responses and genetic diversity.

Helicobacter pylori synthesizes an unusual GroES homolog, heat shock protein A (HspA). The present study was aimed at an assessment of the serological response to HspA in a group of Chinese patients with defined gastroduodenal pathologies and determination of whether diversity is present in the nucleotide sequences encoding HspA in isolates from these patients. Serum samples collected from 154 patients who had an upper gastrointestinal pathology and the presence of H. pylori defined by biopsy were tested for an immunoglobulin G (IgG) serologic response to H. pylori HspA by an enzyme linked immunosorbant assay. HspA-encoding nucleotide sequences in H. pylori isolates from 14 patients (7 seropositive and 7 seronegative for HspA) were analyzed by PCR and direct sequencing of the PCR products. The sequencing results were compared to those of 48 isolates from other parts of the world. Of the 154 known H. pylori-positive patients, 54 (35.1%) were seropositive for HspA. The A domain (GroES homology) of HspA was highly conserved in the 14 isolates tested. Although the B domain (metal-binding site unique to H. pylori) resembled that in the known major variant, particular amino acid substitutions allowed definition of an HspA variant associated with isolates from East Asia. There were no associations between patient characteristics and HspA seropositivity or amino acid sequences. We confirmed in this study that the clinical outcomes of H. pylori infection are not related to HspA antigenicity or to sequence variation. However, B-domain sequence variation may be a marker for the study of the genetic diversity of H. pylori strains of different geographic origins.

Adult

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

A randomized comparison of acute phase response and endotoxemia in patients with perforated peptic ulcers receiving laparoscopic or open patch repair.

BACKGROUND: In patients with peritonitis from perforated peptic ulcers, we compared acute stress responses, endotoxemia, and bacteremia following laparoscopic or open surgery. PATIENTS AND METHODS: Consecutive patients with peritonitis from perforated peptic ulcers were randomized to receive laparoscopic sutured or open omental repair. Undiluted peritoneal fluid was obtained at surgery for quantitative bacterial and endotoxin (Limulus Amoebocyte Lysate) assay. Serial blood samples were taken at 0, 30, 60, 90, 120, and 180 minutes, and at 12, 24, 48, 72, and 120 hours for determinations of quantitative bacterial and endotoxin assays, interleukin-6 (IL-6), C-reactive protein (CRP), and cortisol. RESULTS: Twenty-two patients were randomized: laparoscopy group (n = 12), open repair group (n = 10). Conversions were required in 3 patients assigned to laparoscopy, leaving 9 patients for analysis. The two groups were comparable in their demographic data, median duration of perforation (13.5 hours versus 10 hours), severity of peritoneal contamination as indicated by viable bacterial count (5.9 x 102 versus 1.5 x 10(2) colony forming unit/mL) and endotoxin concentration in peritoneal fluid (27.2 versus 24.6 EU/mL). No significant endotoxemia or bacteremia was detected in these patients. Median interleukin-6 was highest at 0 hour (1520 versus 962 pg/mL) and fell rapidly following surgery. C-reactive protein peaked at 24 hours and plateaued thereafter. Cortisol was highest intraoperatively and fell thereafter. No difference was noted between the two treatment groups with respect to these inflammatory markers (IL-6 P = 0.19, CRP P = 0.14, cortisol P = 0.56, multivariate analysis of variance). CONCLUSION: Endotoxemia and bacteremia are insignificant in most patients with perforated peptic ulcers. In patients with perforated peptic ulcers, laparoscopic patch repair does not reduce acute stress responses when compared with open surgery.

Acute-Phase Proteins

Analysis of cell cycle regulators: p16INK4A, pRb, and CDK4 in low- and high-grade meningiomas.

Abnormalities in the p16INK4A, CDK4, and Rb genes, which regulate transition through G1 phase of the cell cycle, have been implicated in the progression of diverse types of cancer. To evaluate the involvement of p16INK4A, CDK4, and Rb in the tumorigenesis of meningiomas, the status of these genes or gene products were examined. The genetic alteration of the p16INK4A gene was examined by homozygous deletions and by mutation analysis. The methylation status of the p16INK4A was determined by Southern blotting. Neither homozygous deletions nor point mutations of the p16INK4A gene were observed in any of the 23 meningiomas. Partial rather than complete methylation of the p16INK4A gene at SacII or SmaI sites was shown in five (23.8%) meningiomas. The methylation status of the p16INK4A gene was not consistently associated with the expression of p16INK4A in meningiomas. These results suggest that the true relationship between methylation and expression of p16INK4A may be obscured in a complex manner by various mechanisms that regulate p16INK4A expression. Aberrant expressions of pRb and CDK4 were not observed in any of the meningiomas we examined, indicating that abnormalities of the pRb and CDK4 appear to be rare in meningiomas.

Adolescent

Does eradication of Helicobacter pylori impair healing of nonsteroidal anti-inflammatory drug associated bleeding peptic ulcers? A prospective randomized study.

BACKGROUND: Despite the widely accepted view that Helicobacter pylori is the most important cause of peptic ulcer disease, recent studies have suggested that the microbe protects against nonsteroidal anti-inflammatory drug (NSAID)-associated gastroduodenal lesions and promotes ulcer healing. We investigated the effects of H. pylori eradication on the healing of NSAID-associated bleeding peptic ulcers. METHODS: Chronic NSAID users presenting with peptic ulcer haemorrhage underwent endoscopy to secure haemostasis and to document H. pylori infection by rapid urease test and culture. They were prospectively randomized to receive either omeprazole (20 mg once daily) for 8 weeks or a 1-week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, all given four times daily) plus omeprazole (20 mg once daily) for 8 weeks. Endoscopy was repeated after 8 weeks. Final H. pylori status was determined by a 13C-urea breath test that was performed at least 4 weeks after discontinuation of omeprazole. RESULTS: 195 H. pylori-infected NSAID users, complicated by bleeding ulcers, were randomized to receive omeprazole alone (102) or triple therapy plus omeprazole (93). 174 patients returned for second endoscopy at 8 weeks (91 in the omeprazole group, 83 in the triple therapy group). Urea breath test was negative in 14% in the omeprazole group vs. 92% in the triple therapy group (P < 0.001). Complete ulcer healing was achieved in 88 (97%) patients in the omeprazole group and 77 (93%) in the triple therapy group (P=0. 31). On intention-to-treat analysis, ulcers were healed in 86% of the omeprazole group and 83% of the triple therapy group (P=0.50). There was no significant difference in the healing rates of gastric or duodenal ulcers between the two groups. CONCLUSION: Eradication of H. pylori did not impair the healing of NSAID-associated bleeding peptic ulcers.

Adult

Common bile duct stones become smaller after endoscopic biliary stenting.

BACKGROUND AND STUDY AIMS: Endoscopic biliary stenting is often used for large or difficult common bile duct (CBD) stones that cannot be extracted at one session. We compared the sizes of the CBD stones after a period of stenting. PATIENTS AND METHODS: Over a 6-year period, a total of 444 patients with large CBD stones (> 2 cm diameter) or difficult CBD stones were managed in our endoscopy unit, of which 46 were treated by endoscopic stenting. Twenty-eight had second ERCP for stone removal after a median period of 63 days (range 17-1002 days). The largest diameter of the stones and the CBD (after correction of magnification) before and after stenting were compared using the Wilcoxon signed test. RESULTS: Before stenting the largest diameters of CBD stones were 11-46 mm (mean 24.9 mm) and decreased to 5-46 mm (mean 20.1 mm) after stenting. The difference in stone sizes was statistically significant although the CBD diameter pre- and post-stenting was not significantly different. The reduction in stone sizes was not significantly correlated with the duration of stenting. CONCLUSION: CBD stones became smaller after stenting. As the difficulty of stone extraction increases with stone size, a period of stenting may make subsequent removal easier for patients with large or difficult CBD stones.

Aged

Ulcer recurrence after gastric surgery: is Helicobacter pylori the culprit?

OBJECTIVES: Helicobacter pylori is the most important cause of recurrent peptic ulcer disease. However, its role in ulcer recurrence after peptic ulcer surgery is unclear. We aimed at studying the prevalence and distribution of H. pylori in patients who had undergone peptic ulcer surgery, and any association between H. pylori infection and ulcer recurrence in these patients. METHODS: Patients with previous vagotomy or partial gastrectomy presenting with dyspepsia or ulcer bleeding were recruited. Ulcer recurrence was documented by endoscopy. Biopsy specimens were taken from the gastric remnant and gastroenteric anastomosis in patients with previous partial gastrectomy, or from the antrum and corpus in vagotomized patients. H. pylori infection was detected by either a positive rapid urease test or the presence of the bacteria on histology. RESULTS: Ninety-three patients were studied; 73 patients (78%) had partial gastrectomy and 20 (22%) had vagotomy with drainage. H. pylori infection was documented in 36 patients (49%) in the gastrectomy group and in 13 (65%) in the vagotomy group. Thirty-six patients in the gastrectomy group had recurrent ulcers and 15 (42%) of them had H. pylori infection. Twelve patients in the vagotomy group had recurrent ulcers and eight (67%) of them were H. pylori positive. The prevalence of H. pylori infection did not differ between patients with or without ulcer recurrence. CONCLUSION: H. pylori infection cannot account for ulcer recurrence after peptic ulcer surgery.

Adult

Evaluation of a selective transport medium for gastric biopsy specimens to be cultured for Helicobacter pylori.

Since the means of culturing Helicobacter pylori may not be available in some laboratories, prolonging the survival of this organism during transportation is a major concern in terms of improving detection rates. A selective transport medium was evaluated for the preservation of H. pylori from 254 gastric biopsy specimens collected from a rural area in China where culturing is not feasible. Gastric biopsy specimens were inoculated in sterile broth consisting of brain heart infusion (BHI) broth, horse serum, and yeast extract supplemented with vancomycin, amphotericin B, and nalidixic acid (VAN). Of the 254 biopsy specimens, 238 were identified by histology to have H. pylori infection. Total rates of recovery of H. pylori from the H. pylori-positive gastric biopsy specimens stored in the BHI-VAN broth ranged from 76 to 46% after storage of specimens for 5 to 9 days. In conclusion, the selective medium is useful for prolonging the survival of H. pylori in gastric biopsy specimens for which immediate culture is not feasible.

Adult

Expanding allelic diversity of Helicobacter pylori vacA.

The diversity of the gene encoding the vacuolating cytotoxin (vacA) of Helicobacter pylori was analyzed in 98 isolates obtained from different geographic locations. The studies focused on variation in the previously defined s and m regions of vacA, as determined by PCR and direct sequencing. Phylogenetic analysis revealed the existence of four distinct types of s-region alleles: aside from the previously described s1a, s1b, and s2 allelic types, a novel subtype, designated s1c, was found. Subtype s1c was observed exclusively in isolates from East Asia and appears to be the major s1 allele in that part of the world. Three different allelic forms (m1, m2a, and m2b) were detected in the m region. On the basis of sequence alignments, universal PCR primers that allow effective amplification of the s and m regions from H. pylori isolates from all over the world were defined. Amplimers were subsequently analyzed by reverse hybridization onto a line probe assay (LiPA) that allows the simultaneous and highly specific hybridization of the different vacA s- and m-region alleles and tests for the presence of the cytotoxin-associated gene (cagA). This PCR-LiPA method permits rapid analysis of the vacA and cagA status of H. pylori strains for clinical and epidemiological studies and will facilitate identification of any further variations.

Amino Acid Sequence