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Biomedical subjects

K M Chu

Publications and source records attributed to K M Chu.

At least 37 records · Page 2Linked to original sources

Intrafamilial spread of Helicobacter pylori: a prospective study using urea breath test.

PURPOSE: The mode of Helicobacter pylori spread is not well defined. Urea breath test (UBT) is an accurate and noninvasive method for H pylori detection. This study evaluates the role of intrafamilial spread of H pylori using UBT. METHODS: The family members of 16 Hpylori-positive and 16 negative (control) children confirmed by histology and rapid urease test were investigated with UBT. A 58% change was considered positive. RESULTS: A total of 139 persons (72 in the positive group; 67 in the control group) were studied. Fifty-eight (81%, 58 of 72) and 13 (19%, 13 of 67) were found to be positive in the H pylori-positive and control groups, respectively (P < .01). Among children from 19 positive mothers, the positive rate was 60% (25 of 42), whereas among children of negative mothers, the positive rate was 16% (4 of 25; P < .01). The positive rate among children of positive fathers was 66% (23 of 35), whereas that among children of negative fathers was 30% (7 of 23; P < .01). When both parents were H pylori-positive, the children's positive rate was 83% (19 of 23); when both parents were negative, the children's positive rate was 0% (0 of 9; P < .01). CONCLUSIONS: There is strong evidence of intrafamilial spread of H pylori. The positivity of parents with H pylori has an important bearing on their children's H pylori status.

Adolescent↗

Delayed onset of amaurosis fugax in a patient with type A aortic dissection post surgical repair.

Stroke is an important complication for the surgical treatment of type A aortic dissection and it occurs immediately post operation. Many surgical techniques such as deep hypothermic circulatory arrest and retrograde cerebral perfusion have been reported to ameliorate this complication. We report here a male Taiwanese patient with type A aortic dissection involving the arch who underwent surgical repair. Amaurosis fugax appeared on the 4th day post operation. Funduscopic findings demonstrated multi focal embolization and carotid sonography revealed normal carotid arteries. The symptoms and signs improved after anticoagulation therapy. This is a rare case of delayed onset of amaurosis fugax in a patient with type A aortic dissection post surgical repair. The thromboemboli might have originated from the internal surface of the sawing area.

Adult↗

hMLH1 promoter methylation and lack of hMLH1 expression in sporadic gastric carcinomas with high-frequency microsatellite instability.

Mutation of DNA mismatch repair genes has rarely been documented in sporadic gastric carcinoma with microsatellite instability (MSI). In sporadic colorectal carcinoma, hMLH1 promoter methylation associated with protein loss is found in the majority of high-frequency MSI cases. We investigated a series of 35 sporadic gastric carcinomas stratified into high-frequency MSI (MSI-H), low-frequency MSI (MSI-L) and microsatellite stable (MSS) groups and found that hypermethylation of the CpG island in the hMLH1 promoter region was present in 100% of MSI-H sporadic gastric carcinomas. In 90% of cases, there was an associated complete loss of hMLH1 protein, as detected by immunohistochemistry, and a markedly lowered hMLH1 mRNA level. This loss of hMLH1 protein occurred in the MSI-H invasive tumor but not in the adjacent carcinoma-in situ or dysplastic components that were MSS. The MSI-L and MSS forms of gastric carcinoma all showed predominantly unmethylated hMLH1 promoter, positive hMLH1 protein and high hMLH1 mRNA level. On the other hand, hMSH2 protein was expressed in all of the tumors irrespective of the MSI status. Our results suggest that high-frequency MSI in sporadic gastric cancer is mostly due to epigenetic inactivation of hMLH1 in association with promoter methylation, and the loss of hMLH1 protein is a significant event in the development of invasive tumor.

Adaptor Proteins, Signal Transducing↗

Intrahepatic cholangiocarcinoma in Hong Kong.

We retrospectively analyzed the results of hepatic resection for patients with intrahepatic cholangiocarcinoma managed between December 1966 and January 1998 at the University of Hong Kong Medical Center, Queen Mary Hospital. There were 61 men and 40 women (mean age, 61.8 years). The clinical records of these patients were reviewed. A survival analysis was performed on the group of patients who had undergone hepatic resection. Twenty-one patients were treated conservatively. Non-resective (palliative) operations were performed in 32 patients. The median survivals after conservative management and palliative operation were 2.5 and 3.3 months, respectively. The remaining 48 patients underwent hepatic resection. The overall operative morbidity and mortality rates after hepatic resection were 41.7% and 16.7%, respectively. The median survival after hepatic resection was 16.4 months. The overall 1-, 3-, and 5-year survival rates after hepatic resection were 60.3%, 29.4% and 22.0%, respectively. Lymphatic permeation (P = 0.007) and hilar nodal metastases (P = 0.009) were found to be significantly associated with poor survival after hepatic resection. Hepatic resection is the treatment of choice for intrahepatic cholangiocarcinoma when it is resectable.

Adolescent↗

Helicobacter pylori status and endoscopy follow-up of patients having a history of perforated duodenal ulcer.

BACKGROUND: The aim of this study was to determine whether the recurrence of symptoms or ulcer disease in patients with a history of perforated duodenal ulcer is related to Helicobacter pylori infection. METHODS: One hundred sixty-three consecutive patients with history of perforated duodenal ulcer unrelated to nonsteroidal anti-inflammatory drugs underwent upper endoscopy. Any recurrent symptoms or complications were documented. Regardless of the endoscopic findings, three antral biopsy specimens were taken for histologic examination and a rapid urease test. RESULTS: There was a preponderance of men (male/female = 5.3:1). The mean age was 55.9 years. Sixty-seven (41.1%) patients gave a history of recurrent epigastric pain, seven of whom also had a history of bleeding ulcer. Upper endoscopy was performed at a mean of 74.5 +/- 7.1 months after operation. Positive endoscopic findings were noted in 68 (41.7%) patients; H. pylori was found in the biopsy specimens from 77 (47.2%) patients. Recurrent duodenal ulcer was found in 29 (17.8%) patients and was significantly related to male gender, recurrent epigastric pain, bleeding ulcer, longer interval from previous operation, and positive H. pylori status. Positive H. pylori status and male gender were independent factors associated with recurrent duodenal ulcer. CONCLUSIONS: Recurrent ulcer disease in patients with a history of perforated duodenal ulcer is related to H. pylori infection.

Adolescent↗

Microsatellite instability, Epstein-Barr virus, mutation of type II transforming growth factor beta receptor and BAX in gastric carcinomas in Hong Kong Chinese.

Microsatellite instability (MI), the phenotypic manifestation of mismatch repair failure, is found in a proportion of gastric carcinomas. Little is known of the links between MI and Epstein-Barr virus (EBV) status and clinicopathological elements. Examination of genes mutated through the MI mechanism could also be expected to reveal important information on the carcinogenic pathway. Seventy-nine gastric carcinomas (61 EBV negative, 18 EBV positive) from local Hong Kong Chinese population, an intermediate-incidence area, were examined. Eight microsatellite loci, inclusive of the A10 tract of type II transforming growth factor beta receptor (TbetaR-II), were used to evaluate the MI status. MI in the BAX and insulin-like growth factor II receptor (IGF-IIR) genes were also examined. High-level MI (>40% unstable loci) was detected in ten cases (12.7%) and low-level MI (1-40% unstable loci) in three (3.8%). High-level MI was detected in two EBV-associated cases (11%) and the incidence was similar for the EBV-negative cases (13%). The high-level MIs were significantly associated with intestinal-type tumours (P = 0.03) and a more prominent lymphoid infiltrate (P = 0.04). Similar associations were noted in the EBV-positive carcinomas. The high-level MIs were more commonly located in the antrum, whereas the EBV-associated carcinomas were mostly located in body. Thirteen cardia cases were negative for both high-level MI and EBV. All patients aged below 55 were MI negative (P = 0.049). Of the high-level MIs, 80% had mutation in TbetaR-II, 40% in BAX and 0% in IGF-IIR. Of low-level MIs, 33% also had TbetaR-II mutation. These mutations were absent in the MI-negative cases. Of three lymphoepithelioma-like carcinomas, two cases were EBV positive and MI negative, one case was EBV negative but with high-level MI. In conclusion, high-level MIs were present regardless of the EBV status, and were found in a particular clinicopathological subset of gastric carcinoma patient. Inactivation of important growth regulatory genes observed in these carcinomas confirms the importance of MI in carcinogenesis.

Adult↗

Helicobacter pylori in Meckel's diverticulum with heterotopic gastric mucosa in a population with relatively high H. pylori prevalence rate.

BACKGROUND: Helicobacter pylori (H. pylori) colonize only foveolar gastric-type mucosa and are associated with active chronic gastritis and peptic ulcer. The aim of this study was to investigate whether H. pylori can also be found in Meckel's diverticulum which contains heterotopic gastric mucosa. METHODS: Biopsy specimens of Meckel's diverticulum resected in Queen Mary Hospital, University of Hong Kong, during the 10 year period 1986-1995 were retrieved and reviewed. Those containing gastric heterotopia were examined for the presence of H. pylori, using Warthin-Starry silver stain. RESULTS: In the 59 cases of Meckel's diverticula studied, 16 were found to contain heterotopic gastric mucosa. Helicobacter pylori were not identified in any of these cases. In one of the 16 patients a concomitant gastric biopsy was performed. Although the gastric mucosa of this patient was heavily colonized by H. pylori, again no H. pylori was found in the heterotopic gastric mucosa in the Meckel's diverticulum. CONCLUSIONS: The absence of H. pylori in all the Meckel's diverticula examined, even when the stomach was heavily colonized by the organisms, suggests that colonization of Meckel's diverticulum by H. pylori is a rare event. This, together with the overall rarity of H. pylori in all reported series of Meckel's diverticulum, argues against its causative role in complications of Meckel's diverticulum.

Adult↗

Esophageal carcinoma in a patient with bleeding esophageal varices.

More than 20 cases of esophageal carcinoma have been reported to develop after endoscopic injection sclerotherapy (EIS), and this technique is implicated in the pathogenesis of esophageal cancer. We report a case of esophageal carcinoma presenting as a superficial ulcer in a patient with esophageal varices with no prior EIS. Whether the development of esophageal carcinoma in patients with previous EIS is coincidental or consequential is controversial. Such carcinoma might have already existed before EIS in some reported cases. A causal relationship between EIS and esophageal carcinoma cannot be established without further clarification by a well-designed study.

Adenocarcinoma↗

Fosinopril: pharmacokinetics and pharmacodynamics in Chinese subjects.

This study examined thepharmacokinetics and pharmacodynamics of fosinopril (IVand oral) in Chinese subjects to determine whether they were different from a group of somewhat heavier and older Western control subjects previously published using the same methods. It was an open-label, randomized, balanced, two-way crossover study comparing oral and IV pharmacokinetics in 12 healthy Chinese subjects in a clinic in Taiwan. Each subject received 10 mg of oral fosinopril or 7.5 mg of IV fosinoprilatin a randomized sequence with sampling for fosinoprilat concentrations over 48 hours. Standard pharmacokinetics, including AUC, Cmax Tmax, T 1/2, Vss, bioavailability, total clearance, and renal and nonrenal clearance, were determined as well as pharmacodynamic effects on angiotensin-converting enzyme (ACE) activity. Following oral administration of 10 mg fosinopril, AUC0-T and AUCinf were 1,556 +/- 586 ng x hr/mL and 1,636 +/- 620 ng x hr/mL, respectively; T 1/2 was 17.4 +/- 11.4 hr; Cmax was 183.4 +/- 59.4 ng/mL; and median Tmax was 4.0 hr, with > 99% protein binding. Following IV administration of 7.5 mg fosinoprilat, AUC0-T and AUCinf were 7,727 +/- 2,638 ng x hr/mL and 7,816 +/- 2,693 ng x hr/mL, respectively; T 1/2 was 13.0 +/- 5.2 hr; and median Tmax was 4.0 hr, with 99.5% +/- 0.22% protein binding and a Vss of 5,850 +/- 2,780 mL. Bioavailability was 22.3% +/- 7.9%. Percent urinary excretion was 7.6% +/- 2.6% after oral dosing and 42.6% +/- 6.1% after IV dosing. After IV, dosing total clearance was 1,088 +/- 439 mL/hr, renal clearance was 472 +/- 213 mL/hr, and nonrenal clearance was 617 +/- 246 mL/hr. ACE inhibition was essentially complete through 12 hours and markedly reduced through 24 hours. Compared to a somewhat heavier and older previously reported control group, pharmacokinetic values were similar except for a slightly lower AUC and total clearance in Chinese and a statistically significantly lower nonrenal clearance. Pharmacodynamic effects on ACE activity were essentially identical. There is no reason to expect significant differences in fosinopril dosing or effect in a Chinese population compared to a Western population.

Administration, Oral↗

Cardiovascular effect and simultaneous pharmacokinetic and pharmacodynamic modeling of pimobendan in healthy normal subjects.

Pimobendan is a new inotropic agent with vasodilator properties. We have reported the pharmacokinetics of enantiomers of pimobendan in healthy humans. The present report focuses on the pharmacodynamic effect of pimobendan and a simultaneous pharmacokinetic-pharmacodynamic modeling. Eight normal healthy volunteers were studied with oral administration of 7.5 mg and i.v. administration of 5 mg of racemic pimobendan. Concentrations of enantiomers of pimobendan were determined by high performance liquid chromatography. Cardiovascular effects of pimobendan were evaluated by echocardiography. Oral pimobendan significantly reduced 29.0% and 16.5% of the left ventricle end-systolic dimension (LVESD) and end-diastolic dimension, respectively. The mean velocity of circumferential fiber shortening, ejection fraction, and fractional shortening significantly increased 105.9%, 29.8%, and 46% from their baseline values, respectively. The cardiovascular effects of i.v. pimobendan were similar but to a lesser extent. Plots of effect versus plasma concentration (Cp) showed counterclockwise hysteresis loops. A hypothetical effect compartment was established and incorporated into a sigmoid Emax model to describe the time courses of Cps of pimobendan and effects on LVESD. The maximal changes (Emax) in LVESD would be 2.60 +/- 0.51 cm and 2.30 +/- 0.13 cm as estimated from plasma data of (+)- and (-)-pimobendan, respectively. The estimated effect-site concentrations corresponding with 50% of the maximal effect (Ce50) were 6.54 +/- 1.35 and 6.64 +/- 1.35 ng/ml for (+)- and (-)-pimobendan, respectively. A simultaneous pharmacokinetic-pharmacodynamic model could be established to suppress the hysteresis loop and to predict the pharmacological effect based on Cp.

Administration, Oral↗

Helicobacter pylori infection: the reduced need for ulcer surgery.

The success of the eradication treatment for Helicobacter pylori in managing ulcer disease has further refined the indications for ulcer surgery. More patients are spared unnecessary surgery and its untoward sequelae. It is intriguing that surgery has been effective, given that Helicobacter pylori infection is the underlying culprit. Recent studies show that the prevalence of Helicobacter pylori infection remains high after a vagotomy but is more markedly reduced following a partial gastrectomy. Such a reduction may be due to the removal of distal stomach, which is the usual site of infection. In addition, bile appears to be bactericidal to Helicobacter pylori. The association between Helicobacter pylori infection and perforated duodenal ulcer has not been completely settled. A recent study demonstrates that male gender and positive Helicobacter pylori status are independent factors that are associated with recurrent duodenal ulcer after surgery for perforation. Hence, eradication therapy should be given to any patient who has a Helicobacter pylori infection, after surgery has been performed for perforated duodenal ulceration.

Journal Article↗

Quality of life in patients with cancer of the esophagus and gastric cardia: a case for palliative resection.

OBJECTIVE: To evaluate quality-of-life (QOL) parameters in patients undergoing esophagectomy, curative or palliative, for carcinoma. DESIGN: Nonconsecutive case series. PATIENTS: Eighty-eight patients who underwent esophagectomy for cancer (curative, n=49 [56%]; palliative, n=39 [44%]) provided QOL assessments over an 18-month period. SETTING: Procedures for referral care were performed by a single team of clinicians in a tertiary referral center. Evaluations of QOL were made by 1 independent trained investigator. OUTCOME MEASURES: Data were documented by questionnaire at interview and parameters evaluated included an esophageal module for the type and quantity of food intake, severity of related symptoms on eating, Eastern Cooperative Oncology Groups (ECOG) performance status, sleep, pain, leisure activity, working capacity, outlook on life, general well-being, and support from family and friends. A summation of selected parameters was used to calculate a total score. RESULTS: Significant improvements were recorded in both the curative and palliative groups for at least 1 year following surgery in the type (P<.03) and quantity (P<.03) of food intake and severity of diet-related symptoms (P<.02), when compared with preoperative considerations. Findings were comparable between the groups with regard to dietary intake. Pain status and total scores were worse in the palliative group at 9 months postoperatively but no significant differences between the groups were evident at any time for sleep, leisure activity, and ECOG performance status. CONCLUSIONS: To our knowledge, there are no previous data regarding a comparison of QOL considerations in patients who have undergone either potentially curative or palliative esophagectomy for malignant disease. Data analysis revealed that palliative esophagectomy provided enhanced QOL with marked symptomatic benefits and enjoyment of daily living comparable to that observed following curative resection.

Cardia↗

The significance of histologically infiltrated resection margin after esophagectomy for esophageal cancer.

BACKGROUND: Microscopic tumor infiltration of the resection margin after esophageal resection is implicated to influence anastomotic leakage, tumor recurrence rates, and long-term survival. METHODS: Patients with tumor infiltration of resection margin (RM+) and those without (RM-) were compared. RESULTS: Of 604 patients, 45 (7.5%) were RM+. Patients in the RM+ group had more palliative resections, 76% versus 56%, P = 0.01. Anastomotic leakage rates were 2.2% (RM+) and 4.1% (RM-), P = 1.0. Excluding hospital deaths, anastomotic recurrences developed in 10.3% in the RM+ group and 4.9% in the RM- groups, P = 0.15. Although a positive margin did not increase anastomotic recurrence, a shorter resection margin correlated with such recurrence. The mean (SEM) lengths of resection margins in surgical specimens were 2.7 cm (0.3) and 4.4 cm (0.1) for those with and without recurrence, P < 0.001. Median survival time were 8.8 months (RM+) and 15 months (RM-), P = 0.007. CONCLUSIONS: Histologic infiltration of resection margins did not influence leakage rate. Anastomotic recurrence was related to the length of resection margin.

Adult↗

Multiple primary cancers in esophageal squamous cell carcinoma: incidence and implications.

BACKGROUND: The occurrence of multiple primary cancers in the aerodigestive tract is a well-known phenomenon. This study aims to elucidate the incidence and the therapeutic and prognostic implications of a nonesophageal primary cancer in patients with squamous cell carcinoma of the esophagus. METHODS: Between 1982 and 1996, 1,055 patients with esophageal squamous cell carcinoma treated at our institution were reviewed for the presence of an additional primary cancer. The effects of the nonesophageal cancer on treatment of the esophageal carcinoma and survival were analyzed. RESULTS: Among 1,055 patients, 114 nonesophageal primary cancers were documented in 100 patients (9.5%), 70% of which were aerodigestive tract cancers. Forty-seven patients had antecedent tumors and 43 had synchronous tumors. Treatment strategies for esophageal carcinoma in these patients were similar to patients without multiple tumors, not influenced by the nonesophageal tumor except in 6 patients. The overall survival of patients with antecedent tumors, synchronous tumors, and without multiple tumors was similar (median survival, 8.6, 8.5, and 8.8 months, respectively) (p = 0.84). Subsequent primary cancers developed in 10 patients (0.9%), 9 of them with previous curative resection of esophageal cancer, and all died of the subsequent cancer. CONCLUSIONS: There is a high incidence of multiple primary cancers in patients with esophageal carcinoma but the treatment and prognosis of these patients are primarily determined by the esophageal carcinoma itself. Subsequent cancer is, however, a significant cause of death among patients cured of esophageal carcinoma.

Alcohol Drinking↗

Antiulcer drug prescribing in hospital successfully influenced by "immediate concurrent feedback".

OBJECTIVE: To determine whether immediate concurrent feedback (ICF) focused on inpatient omeprazole prescribing achieved more rational and cost-effective antiulcer drug prescribing and usage. METHODS: In a 1400-bed teaching hospital, an audit (by specially trained personnel) was conducted to monitor inpatient prescribing of omeprazole (1) in preference to H2-antagonists and other drugs according to agreed criteria (Helicobacter pylori eradication, severe reflux esophagitis, rapid ulcer healing deemed urgent because of severe symptoms or complications, high-dose steroid therapy of > or =30 mg/day prednisolone) and (2) appropriateness of intravenous dosing (oral route not feasible or contraindicated). After baseline monitoring for 1 month, followed by relevant antiulcer drug therapy education, ICF was instituted for 1 year. This entailed explanatory memoranda requesting a change in prescribing issued to the respective medical teams of patients whose omeprazole prescription did not "conform." The main outcomes of the study were omeprazole prescription numbers per month and the proportion conforming, defined daily doses of antiulcer drugs used and corresponding expenditures, and pertinent antiulcer drug utilization data from 9 other local hospitals. RESULTS: Baseline omeprazole prescribing conformed in 32 of 173 (18%) of the patients compared with 451 of 546 (83%) during institution of ICF (P < 0001; chi2 test). Correspondingly, average overall omeprazole and ranitidine usage (inpatient and outpatient) and expenditure decreased (44% and 45%, respectively); collectively, use of less expensive alternatives increased about 61%. Estimated savings averaged about HK$150,000 ($20,000) per month. No comparable changes in usage were noted in 9 other local hospitals. CONCLUSION: Regarding hospital antiulcer drugs, this ICF strategy was associated with more rational prescribing and usage, and an important saving of resources.

Administration, Oral↗

A prospective randomized trial comparing the use of the flexible gastroscope versus the bronchoscope in the management of foreign body ingestion.

BACKGROUND: Foreign body ingestion is a common clinical problem in Hong Kong. Some recent reports have proposed the use of flexible nasoendoscopy for foreign body retrieval. The present study is a prospective randomized trial on the use of the flexible gastroscope and bronchoscope in the management of foreign body ingestion. METHODS: Two hundred sixteen patients older than 11 years were prospectively randomized to flexible endoscopic examination using either the gastroscope (108 patients) or the bronchoscope (108 patients). The duration of the procedure was noted. Patients were asked to assess their overall tolerance to the procedure on a scale of 1 (well tolerated) to 10 (unacceptable). RESULTS: A foreign body was retrieved in 68 patients (31.5%). There was no difference between the two groups in the foreign body retrieval rate, type of foreign body retrieved, duration of procedure, and tolerance level. In the group managed with the bronchoscope, however, three patients required the additional use of the gastroscope for foreign body retrieval at (for one patient) or below (for two patients) the cricopharyngeus. The patient's tolerance level was related only to the duration of procedure (rho = 0.386; p < 0.001). CONCLUSION: The use of the flexible gastroscope is recommended because of its efficacy, safety, and tolerability.

Adolescent↗

Identification of Leptospira species in the pathogenesis of uveitis and determination of clinical ocular characteristics in south India.

Uveitis is considered a rare complication of leptospirosis. This report describes an epidemic of uveitis among patients with leptospirosis and provides data, using polymerase chain reaction (PCR) amplification of Leptospira DNA, that the pathogenesis is associated with anterior chamber spirochetes. Forty-six uveitis patients, 49 uveitis controls, and 54 cataract controls were enrolled at Aravind Eye Hospital (Madurai, India). Leptospiral DNA was detected by PCR of aqueous humor; serum antibody titers were determined by ELISA and microagglutination (MAT). Thirty-seven uveitis patients (80%) demonstrated leptospiral DNA compared with 5 controls (8%; P < .001). Thirty-three uveitis patients (72%) had positive serology compared with 10 uveitis controls (20%) and 13 cataract controls (24%; P < .001). This report describes the largest cluster of patients with leptospiral uveitis and identifies six clinical characteristics that provide a diagnostic profile for leptospiral uveitis. This profile will be important for determining treatment regimens in countries where PCR and MAT are not available.

Adolescent↗