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Biomedical subjects

J Wong

Publications and source records attributed to J Wong.

At least 73 records · Page 4Linked to original sources

Validity of a modified standard gamble elicited from parents of a hospital-based cohort of children.

OBJECTIVES: To examine the validity of a modified standard gamble (Mod SG) (nondeath baseline) by comparing these scores to SG (death baseline), time trade off (TTO), visual analog scale (VAS), Health Utilities Index (HUI), and Child Health Questionnaire (CHQ). METHODS: Respondents were parents of in-patients with cancer receiving chemotherapy and parents of children without cancer attending outpatient clinics. Construct validity was determined by comparing a priori hypotheses to actual correlations between measures. Discriminant validity was examined by anticipating that in-patients with cancer would have lower HRQL than outpatients. RESULTS: 85 families were included. Both Mod SG and SG were moderately correlated with TTO (r=0.50 and r=0.49; P<.01 for both). Both Mod SG and SG were moderately correlated with TTO (r=0.47 and r=0.05, P<0.002 for both). CONCLUSION: The Mod SG did not perform better than SG. Two nonoverlapping groups of HRQL measures were demonstrated.

Adolescent↗

The possibility of B-cell-dependent T-cell development.

The development of T cells is thought to be independent of B cells. However, defects in cell-mediated immunity in individuals with B-cell deficiency suggest the contrary. To test whether B cells affect T-lymphocyte development, we constructed mice with a monoclonal T-cell compartment (MT) and monoclonal B- and T-cell compartments (MBTs). In these mice, the T cells expressed a DO 11.10 transgenic (DO-T) cell receptor restricted to major histocompatibility complex (MHC) class IId. While CD4+ DO-T lymphocytes are rare in transgenic H-2b MT mice, we found that in H-2b MBT mice under the influence of B cells, DO-T lymphocytes mature into large numbers of CD4+ peripheral T cells. H-2b MBT mice have more CD4+ thymocytes than H-2b MT mice. These data are consistent with the view that B cells play some role in thymocyte development.

Animals↗

Low prevalence of incidentally discovered and early-stage esophageal cancers in a 30-year autopsy study.

Autopsy studies provide information that may guide future patient management. This study analyzed autopsy findings in patients with esophageal cancers, with emphasis on the prevalence of incidentally diagnosed esophageal cancer, histologic subtypes, early-stage lesions, and any associated pathology. Autopsies detected 346 patients (306 men; 40 women) with esophageal carcinomas during a 30-year period, constituting an overall prevalence of 3.4%. Out of these patients, 30 (8.7%) were incidentally discovered at autopsy. Squamous cell cancers were found in 336 (97.1%) patients, small cell cancers in nine (2.7%), and adenocarcinomas in one (0.3%). Stage distributions were stage I in seven patients (2%), stage II in 49 (14%), stage III in 121 (35%), and stage IV in 169 (49%). Isolated dysplasia or carcinoma-in-situ were not found. Comparing with symptomatic patients, patients with incidental cancers were older, had higher frequency of small cell carcinomas, and lower T-stage. The prevalence of incidentally diagnosed esophageal carcinomas and early-stage carcinomas were low. Unusual histologic subtypes may be found.

Adult↗

Docetaxel and carboplatin is an active regimen in advanced non-small-cell lung cancer: a phase II study in Caucasian and Asian patients.

BACKGROUND: The purpose of this study was to report response rates, survival and toxicity in advanced non-small-cell lung cancer (NSCLC) following docetaxel and carboplatin, and to explore potential differences in these end points between Caucasian and Asian patients. PATIENTS AND METHODS: Sixty-eight patients of good performance status with Stage IIIB or IV NSCLC were entered on a phase II study at three sites in Australia and Singapore. Docetaxel 75 mg/m2 and carboplatin AUC 6 were given every 3 weeks. Response to treatment and toxicity were graded by standard criteria. The Kaplan-Meier method was used to estimate survival rates, and subgroups compared by the log-rank test. Cox's proportional hazards regression was used to determine which potentially explanatory variables independently affected the outcome. RESULTS: The response rate was 39% (95% confidence interval 27% to 52%), and 42% in evaluable patients. Response occurred in 65% of Asian and 31% of Caucasian patients (P = 0.01). Ethnicity was the only significant predictor of response in multivariate analysis. The 1-year survival rate was 53%. Performance status (P = 0.021), ethnicity (P = 0.035) and presence of bone or liver metastases (P = 0.011) were independent predictors of overall survival. Neutropenia (grade IV in 73% of patients), febrile neutropenia (26% patients) and diarrhea (grade III/IV in 11% of patients) were the major treatment related toxicities. A high rate (three of six) of febrile neutropenia in Singapore, including one treatment-related death in the initial patients treated, resulted in a reduction in the carboplatin dose to AUC 4.5 at that site. CONCLUSIONS: This regimen is active in advanced NSCLC. The potential impact of ethnicity on efficacy and toxicity of treatment requires further investigation.

Adult↗

The burden of acute postoperative pain and the potential role of the COX-2-specific inhibitors.

Pain has been recognized as a problem of global proportions, and postoperative pain is one of the most common types of pain. Postoperative pain is acute and, although it is preventable and/or treatable, it is often undertreated. Lack of appropriate analgesic management has significant impact on clinical and economic outcomes. Negative clinical outcomes of inadequately managed acute postoperative pain include extended hospitalization, compromised prognosis, higher morbidity and mortality, and the development of a chronic pain state as a result of neuronal plasticity. Although estimating the economic burden of postoperative pain is difficult, this burden is considerable and results from direct costs due to excess health-care resource use, as well as indirect costs due to reduced patient functionality and productivity. These latter factors also have a significant adverse impact on patients' quality of life and may be associated with the development of depression and anxiety. Thus, improved clinical outcomes are dependent not only on the availability of effective drugs but also on their appropriate utilization. A multimodal approach incorporating different drugs and techniques is effective in reducing postoperative pain but is limited by the currently available therapies. The efficacy of opioids is well established, but there are concerns about dependency, respiratory depression and side-effects, which patients often find intolerable. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective as adjunctive medication in a multimodal regimen but are associated with side-effects, such as platelet dysfunction and renal and gastrointestinal toxicity, that have special clinical significance in patients undergoing surgical procedures. Cyclooxygenase-2-specific inhibitors such as celecoxib, rofecoxib and valdecoxib, were developed to provide the efficacy of non-specific NSAIDs while limiting associated toxicity. These agents have demonstrated analgesic efficacy and an opioid-sparing effect in a variety of surgical procedures, suggesting their value as an alternative to non-specific NSAIDs. Further studies are needed to determine the impact of these drugs on clinical and economic outcomes when used in a programme of postsurgical pain management.

Anti-Inflammatory Agents, Non-Steroidal↗

Economic evaluation of oral valdecoxib versus diclofenac in the treatment of patients with rheumatoid arthritis in a randomized clinical trial.

In contrast to economic models that provide probabilistic estimates of economic impact, data extracted from clinical trials may be used to evaluate and compare actual resource utilization and costs. Health-care resource utilization and the costs of these resources were compared from the perspective of the UK National Health Service using data obtained in a 6-month clinical trial of oral valdecoxib 20 mg once daily and diclofenac 75 mg twice daily for the symptomatic treatment of rheumatoid arthritis. However, calculated health-care costs were exclusive of drug acquisition costs because the price of valdecoxib was not available at the time of analysis. While the efficacy of the two treatments was similar, use of valdecoxib was associated with a reduction in total health-care costs amounting to approximately 200 British pounds per patient. This lower cost was associated with reduced use of health-care resources for gastrointestinal serious adverse events (gastrointestinal SAEs). In particular, the incidence of hospitalization and number of hospital days for gastrointestinal SAEs was lower in the valdecoxib group. Analysis of cost per gastrointestinal SAE favoured valdecoxib (cost savings of 742 British pounds), suggesting that even when these events did occur they were less severe. When costs of gastrointestinal SAEs were averaged over the entire population, valdecoxib was suggested to have lower total costs per patient compared with diclofenac (cost savings of 115 British pounds per patient), mainly resulting from significant savings in hospitalization costs (76.49 British pounds per patient). These data are consistent with economic models and suggest that the favourable gastrointestinal profile of valdecoxib observed in clinical trials will be of economic benefit.

Administration, Oral↗

Frequent overexpression of cyclin D1 in sporadic pancreatic endocrine tumours.

Pancreatic endocrine tumours (PETs) occur sporadically or are inherited as part of the multiple endocrine neoplasia type-1 syndrome. Little is known about the molecular events leading to these tumours. Cyclin D1, a key regulator of the G1/S transition of the cell cycle, is overexpressed in a variety of human cancers as well as certain endocrine tumours. We hypothesized that similar to other endocrine tumours, cyclin D1 is overexpressed in human sporadic PETs. Cyclin D1 protein overexpression was found in 20 of 31 PETs (65%) when compared with normal pancreatic tIssue. Furthermore, Northern blot analysis suggests that cyclin D1 up-regulation occurs at the post-transcriptional level in some PETs. Because the key cell growth signalling pathways p42/p44/ERK (extracellular signal-regulated kinase), p38/MAPK (mitogen-activated protein kinase), and Akt/PKB (protein kinase B) can regulate cyclin D1 protein expression in other cell types, pancreatic endocrine tumours were analysed with phospho-specific antibodies against the active forms of these proteins to elucidate a tIssue-specific regulatory mechanism of cyclin D1 in PETs. We found frequent activation of the p38/MAPK and Akt pathways, but down-regulation of the ERK pathway, in cyclin D1 overexpressing PETs. This study demonstrates that cyclin D1 overexpression is associated with human sporadic PET tumorigenesis, and suggests that this up-regulation may occur at the post-transcriptional level. These findings will direct future studies of PETs towards cell cycle dysregulation and the identification of key growth factor pathways involved in the formation of these tumours.

Adenoma, Islet Cell↗

No adverse effect of early weight bearing following open repair of acute tears of the Achilles tendon.

AIM: To study the effects of early weight bearing following acute repair of ruptured Achilles tendon. METHODS: Using a comparative longitudinal study design, following repair of an Achilles tendon rupture, patients in Group 1 were immobilised with their ankle in gravity equinus, were encouraged to weight bear on the operated limb as soon as possible to full weight bearing, and received a single a cast change at 2 weeks, when the ankle was immobilised in a plantigrade position. Patients in Group 2 were immobilised with their ankle in full equinus, and received a cast change at 2 weeks, when the ankle was immobilised in mid equinus, and at 4 weeks, when the ankle was immobilised in a plantigrade position. They were advised to weight bear 4 weeks from the operation. RESULTS: Patients in Group 1 attended less outpatient visits, completely discarded their crutches at an average of 2.5 weeks from the operation (Group 2: average of 5.7 weeks from the operation), (p=0.013), and a greater proportion of them were satisfied with the results of surgery. At ultrasound scan, the average thickness of the repaired tendon was 12.1 mm (SD 2), with no difference in the thickness of the ruptured tendon regardless of the method of postoperative management. There was no significant difference in isometric strength between the two groups of patients. CONCLUSION: Early weight bearing with the ankle plantigrade is not detrimental to the outcome of repair following rupture of the Achilles tendon.

Achilles Tendon↗

Primary gamma-sarcoglycanopathy (LGMD 2C): broadening of the mutational spectrum guided by the immunohistochemical profile.

An important step in the diagnostic evaluation of a patient with recessive limb-girdle muscular dystrophy is the immunohistochemical analysis of the components of the sarcoglycan complex in a muscle biopsy specimen. Even though a primary mutation in any of the four sarcoglycan genes (alpha-, beta-,gamma-, delta-sarcoglycan) may cause secondary deficiencies in all the other sarcoglycan proteins, more specific immunohistochemical patterns have emerged with the potential to guide and abbreviate the necessary molecular genetic investigations. In gamma-sarcoglycan mutations, the pattern consists of absent or prominently reduced gamma-sarcoglycan immunoreactivity in combination with reduced but detectable immunoreactivity for the other components, with preservation of delta-sarcoglycan. In five consecutive patients, this pattern was able to predict primary gamma-sarcoglycan mutations. Five different mutations were found, including a recurrent novel splice mutation, a large deletion of the entire gene and a novel missense mutation (Leu90Ser). The mutation Cys283Tyr, previously restricted to Gypsy populations was found in compound heterozygosity with del521T, common in north Africa. The variety of known and novel mutations found indicates that the immunohistochemical profile of gamma-sarcoglycan mutations is not restricted to a particular mutation or type of mutation, but rather is a general reflection of the effect of gamma-sarcoglycan mutations on the composition of the sarcoglycan complex. Complete immunohistochemical analysis with all available sarcoglycan antibodies, therefore, is a useful tool to guide the molecular genetic investigations that are necessary to arrive at the correct genetic diagnosis in a given case.

Adolescent↗

Right-lobe live donor liver transplantation improves survival of patients with acute liver failure.

BACKGROUND: Right-lobe live donor liver transplantation (LDLT) is used by many liver transplant centres for treating adult patients with terminal liver disease, but its incremental benefit for the intended recipient over cadaveric liver graft transplantation has not been determined. The impact of LDLT as a proactive approach on the outcome of patients with acute liver failure was analysed. METHODS: From January 1999 to March 2001, right-lobe LDLT was offered proactively to 50 consecutive patients with acute liver failure and their families. The outcome of those who opted for right-lobe LDLT (n = 34) was compared with that of those who did not opt for LDLT (n = 16). RESULTS: In the group that opted for right-lobe LDLT, 16 patients eventually received a live donor right-lobe graft (14 patients survived) and three patients received a cadaveric liver graft that became available while the potential live donor was undergoing evaluation (all three patients survived). Among the group who did not opt for LDLT, only one patient received a cadaveric liver graft and survived. The former group had a higher overall survival rate (17 of 34 versus one of 16). With a proactive approach, the overall transplant rate was increased from four of 50 to 20 of 50. The morbidity rate among donors was low and none died. CONCLUSION: Right-lobe LDLT improves the overall survival rate of patients with acute liver failure and should be considered as one of the treatment options for adult patients with acute liver failure.

Adolescent↗

Peripheral nerve regeneration in galactosaemic rats.

The use of galactosaemia as a model for some aspects of diabetic polyneuropathy allows the influence of glycation to be studied independently of other effects. There are well-studied abnormalities of the peripheral nerves in galactosaemic rats, one of which is that the efficiency of regeneration is initially reduced. One possible cause could be that glycated myelin debris in macrophages is less degradable and interferes with macrophage function. Macrophage recognition and ingestion of myelin glycosylated in vitro increases with the duration of incubation in a sugar-rich medium. This study was performed to investigate a possible correlation between galactosaemia and regeneration, together with the role of macrophages. Galactosaemia was induced by adding galactose to the rats' diet for 2 months before injury. Following a crush lesion to the sciatic nerve, regeneration was found to be delayed, demonstrated by a reduction in mean myelinated fibre size and density 1 month after crush, although, 2 and 3 months later, the differences did not reach statistical significance. There were also more macrophages in the galactosaemic rats than in the control animals at all time points. The initial delay in regeneration in galactosaemic rats was therefore only temporary and there was little evidence of long-term deleterious effects. In addition to the morphometric results, immunohistochemistry showed that there were more macrophages in the galactosaemic rats than in the control animals at all time points. Correlating macrophage and myelinated fibre counts suggests that the persistence of debris-containing macrophages does not appear to have a significant inhibitory effect on nerve regeneration. No evidence was found for persistent basal laminal tubes around the regenerating clusters.

Animals↗

Squamous cell carcinoma and adenocarcinoma of the lower third of the esophagus and gastric cardia: similarities and differences.

Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the lower esophagus and gastric cardia were compared in their clinical features and long-term prognosis. Two hundred and ninety-five patients with SCC and 263 with ADC were reviewed. Resectability rates for SCC and ADC were 74.2% and 73.2% respectively (P=0.8). Among those who underwent resection, ADC was more advanced, with 22.3% at stage IV compared with 7.4% for SCC (P=0.001). Postoperative cardiac events occurred in 24.2% of SCC patients and 14.7% of ADC patients (P=0.015), and major respiratory complications in 20.1% and 8.6% respectively (P=0.001). Thirty-day mortality rates were 2.7% and 4% (P=0.46), and hospital mortality rates were 11.4% and 7.6% (P=0.19). Median survival rates were 12.5 months for SCC and 11.6 months for ADC (P=0.99) and 5-year survival rates were 19.9% and 17.6% (P=0.55) respectively. Squamous cell carcinoma of the lower esophagus and ADC of the cardia differed in patient demographics and clinical features but long-term prognoses were similar.

Adenocarcinoma↗

Surgical complications and outcome of pediatric liver transplantation in Hong Kong.

PURPOSE: The aim of this study was to analyze the early and late results of pediatric liver transplantation, with particular reference to complications that required surgical or radiologic intervention. METHODS: The records and code sheets of children who underwent liver transplantation in the authors' institution between September 1993 and December 2001 were reviewed. RESULTS: Twenty-nine children (16 boys and 13 girls) underwent 31 liver transplantations (23 living donor, 8 cadaveric donor) during the study period. The ages of the children ranged from 4 months to 132 months (median, 16 months). Eighteen children had complications that required surgical or radiologic interventional procedures. Complications included, among others, hepatic vein thrombosis (n = 1, 3%), hepatic vein stenosis (n = 2, 7%), portal vein thrombosis (n = 2, 7%), biliary stricture (n = 3, 10%), bile leakage (n = 2, 7%), hepatic artery pseudoaneurysm (n = 1, 3%), jejuno-jejunostomy leakage (n = 1, 3%), graft hepatitis (n = 1, 3%), and posttransplant lymphoproliferative disorder (n = 2, 7%). In addition, 6 children (21%) suffered from intraabdominal bleeding from a variety of causes. After appropriate interventions, at a median follow-up of 38 months (range, 1 to 96 months), patient and graft survival rates were 79% and 74%, respectively. The retransplantation rate was only 7%. There was no incidence of hepatic artery thrombosis. All living donors remain alive and well. CONCLUSIONS: Complications are inevitable in pediatric liver transplantation. However, with timely recognition and active intervention, a good outcome can be achieved.

Child↗

Evaluation of postural stability after low-dose droperidol in outpatients undergoing gynaecological dilatation and curettage procedure.

BACKGROUND: Low-dose droperidol is suggested to be cost-effective in preventing nausea and vomiting after ambulatory surgery. This clinical study evaluated patient postural stability using a computerized force platform after an i.v. dose of droperidol 0.625 mg in outpatients undergoing gynaecological dilatation and curettage procedures. METHODS: After institutional approval and informed consent, 120 females were randomly assigned to receive either 0.9% saline (placebo) or droperidol 0.625 mg i.v. before surgery. Anaesthesia was induced with propofol 2-2.5 mg kg-1 and fentanyl 50-100 micrograms, and was maintained with intermittent boluses of propofol 25-50 mg and fentanyl 25-50 micrograms i.v. After operation, the Post-Anaesthesia Discharge Score (PADS), patient self-assessment scores for pain, nausea, drowsiness and dizziness, and extrapyramidal symptoms were recorded. Body sway velocity was measured while the patient was standing on a firm surface with eyes open then closed vs standing on a foam surface with eyes open then closed, at the time of arrival in the operation holding area (baseline), on achieving a PADS of 9 after surgery and on discharge home. RESULTS: At the time of achieving a PADS of 9, body sway was significantly greater in the droperidol group than in the placebo group (overall 61% vs 33% above baseline). There were no differences between groups with respect to scores for pain, nausea, drowsiness and dizziness. Three patients (5%) in the droperidol group reported nervousness and restlessness postoperatively (not significant). CONCLUSION: Low-dose droperidol 0.625 mg i.v. for anti-emetic prophylaxis can cause balance disturbances in females after gynaecological dilatation and curettage procedures.

Adolescent↗

Comparative analysis of the complete genome sequences of Helicoverpa zea and Helicoverpa armigera single-nucleocapsid nucleopolyhedroviruses.

The complete nucleotide sequence of Helicoverpa zea single-nucleocapsid nucleopolyhedrovirus (HzSNPV) has been determined (130869 bp) and compared to the nucleotide sequence of Helicoverpa armigera (Ha) SNPV. These two genomes are very similar in their nucleotide (97% identity) and amino acid (99% identity) sequences. The coding regions are much more conserved than the non-coding regions. In HzSNPV/HaSNPV, the 63 open reading frames (ORFs) present in all baculoviruses sequenced so far are much more conserved than other ORFs. HzSNPV has four additional small ORFs compared with HaSNPV, one of these (Hz42) being in a correct transcriptional context. The major differences between HzSNPV and HaSNPV are found in the sequence and organization of the homologous regions (hrs) and the baculovirus repeat ORFs (bro genes). The sequence identity between the HzSNPV and HaSNPV hrs ranges from 90% (hr1) to almost 100% (hr5) and the hrs differ in the presence/absence of one or more type A and/or B repeats. The three HzSNPV bro genes differ significantly from those in HaSNPV and may have been acquired independently in the ancestral past. The sequence data suggest strongly that HzSNPV and HaSNPV are variants of the same virus species, a conclusion that is supported by the physical and biological data.

Animals↗

Cost effectiveness of combination therapy for hepatitis C: a decision analytic model.

OBJECTIVE: To estimate the cost utility of treatment with combination therapy (ribavirin and interferon alpha) for hepatitis C compared with no treatment or monotherapy (interferon alpha) based on UK costs and clinical management. DESIGN: Decision analysis model using a Markov approach to simulate disease progression. SETTING: UK secondary care. PARTICIPANTS: Hypothetical cohort of patients with hepatitis C. MAIN OUTCOME MEASURES: Cost per quality adjusted life year (QALY) gained. RESULTS: Discounted cost per QALY for combination therapy over no treatment was 3791 pounds. Cost per QALY varied between 1646 pounds and 9170 pounds according to subgroup, with the lowest ratios being for genotype 2 or 3, women, those aged less than 40 years, and those with moderate hepatitis. The discounted cost per QALY of the combination over monotherapy was 3485 pounds. Similar findings were shown for subgroups as for the comparison with no treatment. One way sensitivity analysis showed that while drug costs were more important in the analysis than assumptions about disease progression or costs of treating hepatitis C disease, the results were robust to large changes in underlying assumptions. CONCLUSIONS: Combination therapy for hepatitis C is a cost effective treatment option and is superior to monotherapy. Considerable uncertainties remain over the appropriate management strategies in the populations excluded from randomised controlled trials and in whom treatment is currently being considered in the UK.

Adult↗