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Biomedical subjects

J C Wu

Publications and source records attributed to J C Wu.

At least 19 recordsLinked to original sources
PubMed2001

RNA folding pathway functional intermediates: their prediction and analysis.

The massively parallel genetic algorithm (GA) for RNA structure prediction uses the concepts of mutation, recombination, and survival of the fittest to evolve a population of thousands of possible RNA structures toward a solution structure. As described below, the properties of the algorithm are ideally suited to use in the prediction of possible folding pathways and functional intermediates of RNA molecules given their sequences. Utilizing Stem Trace, an interactive visualization tool for RNA structure comparison, analysis of not only the solution ensembles developed by the algorithm, but also the stages of development of each of these solutions, can give strong insight into these folding pathways. The GA allows the incorporation of information from biological experiments, making it possible to test the influence of particular interactions between structural elements on the dynamics of the folding pathway. These methods are used to reveal the folding pathways of the potato spindle tuber viroid (PSTVd) and the host killing mechanism of Escherichia coli plasmid R1, both of which are successfully explored through the combination of the GA and Stem Trace. We also present novel intermediate folds of each molecule, which appear to be phylogenetically supported, as determined by use of the methods described below.

Algorithms↗
PubMed2001

Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen.

BACKGROUND: Many patients who have had upper gastrointestinal bleeding continue to take low-dose aspirin for cardiovascular prophylaxis or other non-steroidal antiinflammatory drugs (NSAIDs) for musculoskeletal pain. It is uncertain whether infection with Helicobacter pylori is a risk factor for bleeding in such patients. METHODS: We studied patients with a history of upper gastrointestinal bleeding who were infected with H. pylori and who were taking low-dose aspirin or other NSAIDs. We evaluated whether eradication of the infection or omeprazole treatment was more effective in preventing recurrent bleeding. We recruited patients who presented with upper gastrointestinal bleeding that was confirmed by endoscopy. Their ulcers were healed by daily treatment with 20 mg of omeprazole for eight weeks or longer. Then, those who had been taking aspirin were given 80 mg of aspirin daily, and those who had been taking other NSAIDs were given 500 mg of naproxen twice daily for six months. The patients in each group were then randomly assigned separately to receive 20 mg of omeprazole daily for six months or one week of eradication therapy, consisting of 120 mg of bismuth subcitrate, 500 mg of tetracycline, and 400 mg of metronidazole, all given four times daily, followed by placebo for six months. RESULTS: We enrolled 400 patients (250 of whom were taking aspirin and 150 of whom were taking other NSAIDs). Among those taking aspirin, the probability of recurrent bleeding during the six-month period was 1.9 percent for patients who received eradication therapy and 0.9 percent for patients who received omeprazole (absolute difference, 1.0 percent; 95 percent confidence interval for the difference, -1.9 to 3.9 percent). Among users of other NSAIDs, the probability of recurrent bleeding was 18.8 percent for patients receiving eradication therapy and 4.4 percent for those treated with omeprazole (absolute difference, 14.4 percent; 95 percent confidence interval for the difference, 4.4 to 24.4 percent; P=0.005). CONCLUSIONS: Among patients with H. pylori infection and a history of upper gastrointestinal bleeding who are taking low-dose aspirin, the eradication of H. pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding. Omeprazole is superior to the eradication of H. pylori in preventing recurrent bleeding in patients who are taking other NSAIDs.

Anti-Bacterial Agents↗
PubMed2001

Noninvasive optical imaging of firefly luciferase reporter gene expression in skeletal muscles of living mice.

The ability to monitor reporter gene expression noninvasively offers significant advantages over current techniques such as postmortem tissue staining or enzyme activity assays. Here we demonstrate a novel method of repetitively tracking in vivo gene expression of firefly luciferase (FL) in skeletal muscles of mice using a cooled charged coupled device (CCD) camera. We first show that the cooled CCD camera provides consistent and reproducible results within +/-8% standard deviation from mean values, and a detection sensitivity (range tested: 1 x 10(4) - 1 x 10(9) plaque form-ing units (pfu)) of 1 x 10(6) pfu of E1-deleted adenovirus expressing FL driven by a cytomegalovirus promoter (Ad-CMV-FL). The duration and magnitude of adenoviral mediated (1 x 10(9) pfu) FL gene expression were then followed over time. FL gene expression in immunocompetent Swiss Webster mice peaks within the first 48 hours, falls by 98% after 20 days, and persists for >150 days. In contrast, FL activity in nude mice remains elevated for >110 days. Finally, transduced Swiss Webster and nude mice were sacrificed to show that the in vivo CCD signals correlate well with in vitro luciferase enzyme assays (r(2)=0.91 and 0.96, respectively). Our findings demonstrate the ability of the cooled CCD camera to sensitively and noninvasively track the location, magnitude, and persistence of FL gene expression. Monitoring of gene therapy studies in small animals may be aided considerably with further extensions of this technique.

Adenoviridae↗
PubMed2001

Correlations between theoretical and experimental determination of heat of formation of certain aromatic nitro compounds.

Heats of formation of energetic materials can be obtained either experimentally or theoretically. In order to compare the results of the two methods, some correlation methods were proposed in this study. The molecular structures and heats of formation of nitrobenzenes, nitrotoluenes, nitroanilines, and nitrophenols were calculated by Dewar's AMI and Stewart's PM3 methods. Correlations of heats of formation between the theoretical calculations and experimental results were evaluated by using the multivariable linear regression method. Results indicate that there are very precise correlations. Based on these correlations, heats of formation of some aromatic nitro compounds can be predicted at 95% predictive interval without experimental analysis.

Journal Article↗
PubMed2001

Correlations between theoretical and experimental determination of heat of formation of certain aliphatic nitro compounds.

Heats of formation of energetic materials were calculated by Dewar's AM1 and Stewart's PM3 methods. In order to compare the theoretical results with the experimental ones, some correlation models were proposed in this study. Correlations were evaluated by multivariable linear regression method, considering the number of nitro groups and the use of quadratic relations involving the number of carbon, hydrogen, nitrogen, and oxygen atoms. Results indicated very precise correlations. Based on these correlations, heats of formation of some aliphatic nitro compounds can be predicted at 95% predictive interval without experimental analysis.

Journal Article↗
PubMed2001

Clinical neurochemical implications of sleep deprivation's effects on the anterior cingulate of depressed responders.

The antidepressant and cerebral metabolic effects of total sleep deprivation (TSD) or partial sleep deprivation (PSD) for one night has been studied with functional neuroimaging in seven publications from five different groups. Despite the variations in methods and techniques, the over-all findings were relatively consistent. First, before sleep deprivation, responders have significantly elevated metabolism compared with non-responders and normal controls, in the orbital medial prefrontal cortex, and especially the ventral portions of the anterior cingulate cortex. Second, after sleep deprivation, these hyperactive areas normalize in the responders. One functional imaging study suggested that synaptic dopamine release was associated with the antidepressant effects of TSD. The neurochemical implications of these findings are explored. Possible dopaminergic and serotonergic mechanisms are discussed.

Cerebral Cortex↗
PubMed2001

Brain metabolic and clinical effects of rivastigmine in Alzheimer's disease.

In-vivo metabolic measures with positron emission tomography using (18)F-fluorodeoxyglucose (FDG-PET) have demonstrated hypometabolism in temporal, frontal, and hippocampal areas during the early stages of Alzheimer's disease (AD). Progression of the dementia in AD involves compromised cholinergic functioning. Cholinesterase inhibitors have demonstrated efficacy in improving cognition and behaviour in AD. In this study, we demonstrate the usefulness of FDG-PET in measuring the progression of untreated AD and its modification by treatment with rivastigmine (Exelon, Novartis Pharmaceuticals, East Hanover, New Jersey, USA), a centrally selective cholinesterase inhibitor of the carbamate type. Patients with mild to moderate probable AD (Mini-Mental Status Exam scores of 10-26, inclusive) were enrolled in a double-blind, placebo controlled comparison of three fixed daily doses of rivastigmine (3, 6, or 9 mg/d) or placebo for 26 wk. FDG-PET scans were obtained on 27 patients at baseline and following 26 wk of treatment using the Snodgrass Picture Naming activation task. A total of 71.4% of the patients treated with placebo deteriorated clinically compared to only 25.0% of the patients treated with rivastigmine (chi2 = 4.8; p & 0.03). Rivastigmine-responders (i.e. those who clinically improved or remained clinically stable as measured by the Clinicianaposs Interview-Based Impression of Change-plus) showed a marked increase in brain metabolism (p <0.01) involving, but not limited to, structures comprising the memory-related cortices and the prefrontal system. These metabolic changes were not observed in the placebo-treated patients or the rivastigmine non-responders. Of note is that responders increased hippocampal metabolism by 32.5% (p < 0.03) compared to a non-significant decrease in the non-responders (6.4%) and placebo-treated patients (4.1%). These results are consistent with the literature suggesting that FDG-PET can sensitively measure the progression of AD and its improvement with cholinesterase inhibitors. Rivastigmine prevented the expected deterioration in clinical status and dramatically increased brain metabolic activity in a majority of patients.

Aged↗
PubMed2001

Kidney transplantation in patients with chronic hepatitis B virus infection: is the prognosis worse?

The impact of hepatitis B virus (HBV) infection on the long-term outcome of kidney transplant patients is controversial. A total of 34 chronic hepatitis B surface antigen (HBsAg) carriers among 143 renal allograft recipients were identified in this study (mean follow-up period: 5.6+/-3.3 years; range: 1-13 years). During the follow-up, one HBsAg-positive recipient with preexisting cirrhosis died of liver failure, and seven (21%) others developed serious HBV-related complications (four fulminant hepatitis, two hepatocellular carcinoma, one cirrhosis), and four died. Although HBsAg-positive recipients had a higher rate of liver-related complications and deaths than HBsAg-negative recipients did, there were no significant differences in the long-term graft and patient survival between the two groups. The survival rates, liver-related complications, and deaths in HBsAg-positive allograft recipients and 28 HBsAg-positive uremic patients under dialysis were similar. In conclusion, HBV infection is not a contraindication to kidney transplantation. However, pretransplant candidates should be warned of potentially serious liver-related complications.

Adolescent↗
PubMed2001

Randomized trial of low-dose misoprostol and naproxen vs. nabumetone to prevent recurrent upper gastrointestinal haemorrhage in users of non-steroidal anti-inflammatory drugs.

BACKGROUND: Prophylactic misoprostol or non-steroidal anti-inflammatory drugs (NSAIDs) with low gastric toxicity (nabumetone) has been shown to reduce mucosal injury. AIM: To compare nabumetone vs. co-therapy of naproxen with low-dose misoprostol for secondary prevention of upper gastrointestinal bleeding in NSAID users. METHODS: NSAID users presenting with upper gastrointestinal bleeding were enrolled if they required long-term NSAIDs. After ulcer healing, they were randomized to receive: naproxen (500-1000 mg/day) and misoprostol (200 microg b.d.), or nabumetone (1000-1500 mg/day) and placebo misoprostol for 24 weeks. The primary end-point was recurrent upper gastrointestinal bleeding. The secondary end-point was the proportion of patients suffering from major gastrointestinal events including ulcer bleeding, symptomatic ulcers and severe dyspepsia. RESULTS: A total of 90 patients were included in the intention-to-treat analysis (misoprostol/naproxen 45, nabumetone 45). Recurrent bleeding occurred in 10 patients (22.2%) receiving misoprostol/naproxen compared with three (6.7%) receiving nabumetone (relative risk 3.33, 95% CI: 0.98-11.32, P=0.069). The proportion of patients suffering from major gastrointestinal events at 24 weeks was 31.1% in the misoprostol/naproxen group and 28.9% in the nabumetone group. CONCLUSIONS: Misoprostol/naproxen is not superior to nabumetone for secondary prevention of upper gastrointestinal bleeding. Neither low-dose misoprostol nor nabumetone is adequate for high-risk NSAID users.

Adult↗
PubMed2001

Dysfunction of oesophageal motility in Helicobacter pylori-infected patients with reflux oesophagitis.

BACKGROUND: Helicobacter pylori infection has been suggested to be protective against gastro-oesophageal reflux disease. However, a significant proportion of patients with gastro-oesophageal reflux disease are infected by H. pylori. AIM: To study oesophageal motor function in H. pylori-infected patients with reflux oesophagitis. METHODS: Patients with erosive reflux oesophagitis were recruited prospectively for stationary oesophageal manometry and 24-h ambulatory oesophageal pH monitoring. H. pylori status was determined by biopsy urease test. Non-reflux volunteers were recruited as controls. RESULTS: Seventy-four patients with erosive oesophagitis (34 H. pylori-positive, 40 H. pylori-negative) and 48 non-reflux patient controls (22 H. pylori-positive, 26 H. pylori-negative) were recruited. There was no difference in severity of oesophagitis (median grade, 1; P=0.53) or oesophageal acid exposure (total percentage time oesophageal pH < 4, 7.6% vs. 6.8%; P=0.57) between H. pylori-positive and H. pylori-negative groups. Compared to H. pylori-negative patients, H. pylori-positive patients had significantly lower basal lower oesophageal sphincter pressure (12.2 mmHg vs. 15.3 mmHg; P=0.03) and amplitude of distal peristalsis (56.9 mmHg vs. 68.4 mmHg; P=0.03). Ineffective oesophageal motility (14% vs. 7%; P=0.02) and failed oesophageal peristalsis were also significantly more prevalent in H. pylori-positive patients. CONCLUSIONS: Among patients with a similar degree of reflux oesophagitis, H. pylori-infected patients have more severe oesophageal dysmotility and lower oesophageal sphincter dysfunction. Oesophageal motor dysfunction probably plays a dominant role in the development of gastro-oesophageal reflux disease in patients with H. pylori infection.

Adult↗
PubMed2001

Long-term evaluation of recombinant interferon alpha2b in the treatment of patients with hepatitis B e antigen-negative chronic hepatitis B in Taiwan.

The effect of interferon (IFN) on hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) has not been fully investigated in Chinese patients. We enrolled 58 HBeAg-negative CHB Chinese patients with hepatitis B viremia in Taiwan to evaluate the response to IFN. 30 patients received recombinant IFN 5 million units 3 times weekly for 6-10 months, and 28 patients who refused IFN treatment served as controls. Rates of virological response and biochemical response were higher in the treated group at the end of treatment (57% vs 18%, P = 0.006, and 73% vs 29%, P = 0.002, respectively). Both effects were superior in the treated group at 6 months after IFN withdrawal (virological: 30% vs 7%, P = 0.06; biochemical: 47% vs 7%, P = 0.002). Improvement of liver histological activities with persistently biochemical response was found in 65% of the treated patients. After a mean of 32 months' follow-up, virological response was rarely maintained (17% vs 4%, P = 0.228) but biochemical response was better in the treated group (27% vs 4%, P = 0.039). None of the treated patients but five controls developed severe complications of CHB during the follow-up period. A larger total IFN dosage or a younger age (< or = 40 years) were associated with 'sustained' virological response. Younger age and higher baseline alanine transaminase values (> or = 120 Ul(-1)) were related to 'sustained' biochemical response.

Adult↗
PubMed2001

Ranitidine-related Stevens-Johnson syndrome in patients with severe liver diseases: a report of two cases.

Ranitidine is widely used and well tolerated. Ranitidine-related skin eruption is rare and usually mild. We presented two patients who developed Stevens-Johnson syndrome after ranitidine therapy. Before therapy, both patients had severe liver disease and jaundice. The first was a case of ketoconazole-induced hepatitis, and the second was a case of hepatitis C-related liver cirrhosis with hepatocellular carcinoma. Ranitidine was the most likely drug responsible for causing Stevens-Johnson syndrome in these two patients.

Antifungal Agents↗
PubMed2001

Hepatic steatosis in chronic hepatitis C virus infection: prevalence and clinical correlation.

BACKGROUND AND AIMS: Hepatic steatosis is a histological characteristic in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to evaluate the prevalence of hepatic steatosis in Chinese patients with chronic hepatitis C, and to look for possible correlation with various histopathological changes and to look for possible correlation with various clinical and pathologic variables. METHODS: One hundred and six patients were enrolled, and patients with alcoholism or diabetes mellitus were excluded. Clinical, biochemical and virologic data, including HCV genotype and serum HCV-RNA titer and histological findings, were compared between patients with and without hepatic steatosis. RESULTS: Fifty-five (52%) of the 106 patients with chronic hepatitis C had hepatic steatosis. Patients with hepatic steatosis had significantly higher mean serum levels of triglyceride and gamma-glutamyl transpeptidase, higher body mass index, and a higher incidence of obesity compared with patients without hepatic steatosis. No significant differences in serum HCV-RNA titer and HCV genotype or the response to interferon therapy were noted between the two groups. Histological analysis showed patients with hepatic steatosis had a significantly higher mean fibrotic score than patients without hepatic steatosis (1.9 +/- 1.2 vs 1.3 +/- 1.0; P = 0.016). There were no significant differences in the severity of necroinflammation, the presence of lymphoid aggregation/follicle or bile duct damage between the two groups. Multivariate logistic regression analysis showed that independent predictors associated with hepatic steatosis were obesity or a histology fibrotic score of > or = 2. CONCLUSION: It was found that 52% of Chinese patients with chronic hepatitis C had hepatic steatosis. Patients with hepatic steatosis were more frequently obese and had more severe hepatic fibrosis.

Adult↗
PubMed2001

Comparison of clinical, virologic and pathologic features in patients with acute hepatitis B and C.

BACKGROUND AND AIMS: The clinical outcomes of adult-acquired acute infection of hepatitis C virus (HCV) and hepatitis B virus (HBV) are quite different. In order to compare the clinical, biochemical, virologic and pathologic pictures in these two groups of patients, we enrolled 22 adult patients with acute hepatitis C and 16 adult patients with acute hepatitis B, on whom liver biopsies were performed within 3 months of acute onset of the illness. RESULTS: The results showed that a significantly younger age, a higher ratio of the clinical symptoms of jaundice, nausea, vomiting, and poor appetite, a higher mean serum level of alanine transaminase, aspartate transaminase, and total bilirubin were present in patients with acute hepatitis B patients than in those with acute hepatitis C (P < 0.05). There was a significantly higher degree of periportal inflammation and total necro-inflammatory activity in the acute hepatitis B patients (P = 0.002 and 0.049, respectively). Fifteen (68.2%) of the 22 patients with acute hepatitis C had detectable serum HCV-RNA, but only two (14.3%) of the 14 tested patients with acute hepatitis B had detectable serum HBV-DNA, detected by using the branched DNA signal amplification assay. Eighteen (82%) of the 22 acute hepatitis C patients and none of the 16 acute hepatitis B patients progressed into a chronic hepatitis stage (P < 0.001). CONCLUSION: The manifestations of mild clinical symptoms, lower mean serum transaminases and bilirubin levels, a lesser degree of histological periportal necroinflammation, and more patients with a high circulatory viral load among the acute hepatitis C patients, may lead to more of that group developing chronicity than patients with acute hepatitis B.

Acute Disease↗
PubMed2001

Seasonal variability of the QT dispersion in healthy subjects.

We studied the seasonal variability of QT dispersion in 25 healthy subjects, aged 36 +/- 5 (25 to 46) years. Four seasonal 12-lead rest electrocardiograms (ECGs) recorded at a double amplitude were performed at 25 mm/s at intervals of roughly 3 months. To avoid possible confusion from the circadian rhythm of QT dispersion, subsequent ECGs were recorded within 30 minutes of the reference summer one. The QT dispersion was calculated as the difference between the longest and the shortest mean QT intervals. There was a seasonal variability in the QT dispersion (P =.001), with the largest QT dispersion occurring in winter (66 +/- 21 ms) and the smallest one in spring (48 +/- 18 ms). In conclusion, there exists a seasonal variability of QT dispersion in healthy subjects and such variability should be taken into consideration in comparison of the QT dispersion.

Adult↗
PubMed2001

Is non-Helicobacter pylori, non-NSAID peptic ulcer a common cause of upper GI bleeding? A prospective study of 977 patients.

BACKGROUND: Non-Helicobacter pylori, non-NSAID ulcer is relatively common in Western countries. Whether it is a significant problem in the Orient is unclear. The aim of this study was to investigate the incidence of non-H pylori, non-NSAID ulcers presenting with GI bleeding. METHODS: A prospective study was done of 1675 consecutive patients presenting with upper GI bleeding over a period of 12 months. Upper endoscopy was performed with biopsy specimens taken from the antrum and body of the stomach for a biopsy urease test (BUT) and histology for detection of H pylori. Exposure to nonsteroidal anti-inflammatory drugs (NSAID) or aspirin within 4 weeks of hospitalization was carefully scrutinized. A 6-week course of treatment with an H2-receptor antagonist was prescribed for patients who did not use an NSAID and had a negative BUT result. Follow-up endoscopy was performed to confirm H pylori status with a BUT and histology. Positive histology at either initial or follow-up endoscopy was used as the standard for diagnosing H pylori infection. RESULTS: Among 977 patients who were found to have ulcer bleeding, 434 (44%) had exposure to aspirin or an NSAID. Of the 543 non-NSAID users, 431 (79.4%) had a positive BUT and 112 (20.6%) were BUT negative on initial endoscopy. Eighty-nine of 112 patients who were NSAID negative, BUT negative returned for follow-up endoscopy. Forty-nine of 89 (55.1%) were found to have a positive BUT and positive histology at follow-up endoscopy. Only 40 of 977 (4.1%) patients admitted with ulcer bleeding were confirmed to have non-H pylori, non-NSAID ulcers. CONCLUSIONS: Non-H pylori, non-NSAID bleeding ulcer is uncommon. A negative BUT is unreliable for exclusion of H pylori infection during the acute phase of ulcer bleeding.

Adolescent↗
PubMed2001

Incidence of gastroesophageal malignancy in patients with dyspepsia in Hong Kong: implications for screening strategies.

BACKGROUND: A "test-and-treat" strategy for H pylori infection has been recommended in Europe and North America as safe and cost-effective for management of patients with dyspepsia. The primary aim of this study was to determine the frequency of gastroesophageal cancer in 2 groups of patients with dyspepsia: those 45 years of age or younger without "alarm" symptoms (low-risk group) and patients over 45 years of age or any patient with "alarm" symptoms (high-risk group). A secondary aim was to determine the frequency of gastric cancer among patients in the low-risk group with or without a positive serology for H pylori. METHODS: Patients with persistent dyspepsia were recruited from 4 regional hospitals in Hong Kong. Those in the low-risk group were evaluated for H pylori by using a whole blood serology test; they underwent endoscopy within 1 week. Those in the high-risk group and those taking nonsteroidal anti-inflammatory drugs (NSAIDs) underwent endoscopy promptly. Alarm symptoms were as follows: weight loss (10 or more pounds over 8 weeks), recurrent vomiting, dysphagia, bleeding, or anemia. RESULTS: Of 2627 patients enrolled, 1017 were in the low-risk group and 1610 in the high-risk group. Twenty-three patients (0.9%) had gastroesophageal cancers (20 gastric, 3 esophageal). Four patients with cancer (17.4%) were in the low-risk group (3 gastric, 1 esophageal); all except the patient with esophageal cancer had a positive serology test. In the high-risk group, 19 patients had cancer (17 gastric, 2 esophageal). CONCLUSION: Gastric cancer is relatively frequent among young patients with dyspepsia who have no alarm features in Hong Kong. This finding raises concerns as to the safety of the "test-and-treat" strategy for the management of patients with dyspepsia in Asia.

Adult↗