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Biomedical subjects

M Wong

Publications and source records attributed to M Wong.

At least 37 records · Page 2Linked to original sources
PubMed2003

Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial.

Prevalent vertebral fractures and baseline bone mineral density (BMD) predict subsequent fracture risk. The objective of this analysis is to examine whether baseline vertebral fracture severity can predict new vertebral and nonvertebral fracture risk. In the randomized, double-blind 3-year Multiple Outcomes of Raloxifene Evaluation (MORE) trial, 7705 postmenopausal women with osteoporosis (low BMD or prevalent vertebral fractures) were randomly assigned to placebo, raloxifene 60 mg/day, or raloxifene 120 mg/day. Post hoc analyses studied the association between baseline fracture severity and new fracture risk in the placebo group and the effects of placebo, raloxifene 60 mg/day, and raloxifene 120 mg/day on new fracture risk in women with the most severe prevalent vertebral fractures (n = 614). Vertebral fracture severity was visually assessed using semiquantitative analysis of radiographs and categorized by estimated decreases in vertebral heights. Reported new nonvertebral fractures were radiographically confirmed. Baseline vertebral fracture severity predicted vertebral and nonvertebral fracture risk at 3 years. In women without prevalent vertebral fractures, 4.3 and 5.5% had new vertebral and nonvertebral fractures, respectively. In women with mild, moderate, and severe prevalent vertebral fractures, 10.5, 23.6, and 38.1% respectively had new vertebral fractures, whereas 7.2, 7.7, and 13.8% respectively experienced new nonvertebral fractures. Number of prevalent vertebral fractures and baseline BMD also predicted vertebral fracture risk, but the severity of prevalent vertebral fractures was the only predictor of nonvertebral fracture risk and remained a significant predictor after adjustment for baseline characteristics, including baseline BMD. In patients with severe baseline vertebral fractures, raloxifene 60 mg/day decreased the risks of new vertebral [RR 0.74 (95% Cl 0.54, 0.99); P = 0.048] and nonvertebral (clavicle, humerus, wrist, pelvis, hip, and leg) fractures [RH 0.53 (95% CI 0.29, 0.99); P = 0.046] at 3 years. To prevent one new fracture at 3 years in women with severe baseline vertebral fractures with raloxifene 60 mg/day, the number needed to treat (NNT) was 10 for vertebral and 18 for nonvertebral fractures. Similar results were observed in women receiving raloxifene 120 mg/day. In summary, baseline vertebral fracture severity was the best independent predictor for new vertebral and nonvertebral fracture risk. Raloxifene decreased new vertebral and nonvertebral fracture risk in the subgroup of women with severe vertebral fractures at baseline. These fractures may reflect architectural deterioration, independent of BMD, leading to increased skeletal fragility.

Aged↗
PubMed2003

Identification of candidate genes for psychosis in rat models, and possible association between schizophrenia and the 14-3-3eta gene.

Although the genetic contribution to schizophrenia is substantial, positive findings in whole-genome linkage scans have not been consistently replicated. We analyzed gene expression in various rat conditions to identify novel candidate genes for schizophrenia. Suppression subtraction hybridization (SSH), with polyA mRNA from temporal and frontal cortex of rats, was used to identify differentially expressed genes. Expression of mRNA was compared between adult Lewis and Fischer 344 (F344) rats, adult and postnatal day 6 (d6) F344, and adult F344 treated with haloperidol or control vehicle. These groups were chosen because each highlights a particular aspect of schizophrenia: differences in strain vulnerability to behavioral analogs of psychosis; factors that may relate to disease onset in relation to CNS development; and improvement of symptoms by haloperidol. The 14-3-3 gene family, as represented by 14-3-3gamma and 14-3-3zeta isoforms in the SSH study, and SNAP-25 were among the candidate genes. Genetic association between schizophrenia and the 14-3-3eta gene, positioned close to a genomic locus implicated in schizophrenia, and SNAP-25 genes was analyzed in 168 schizophrenia probands and their families. These findings address three different genes in the 14-3-3 family. We find a significant association with schizophrenia for two polymorphisms in the 14-3-3eta gene: a 7 bp variable number of tandem repeats in the 5' noncoding region (P=0.036, 1 df), and a 3' untranslated region SNP (753G/A) that is an RFLP visualized with Ava II (P=0.028). There was no significant genetic association with SNAP-25. The candidate genes identified may be of functional importance in the etiology, pathophysiology or treatment response of schizophrenia or psychotic symptoms. This is to our knowledge the first report of a significant association between the 14-3-3eta-chain gene and schizophrenia in a family-based sample, strengthening prior association reports in case-control studies and microarray gene expression studies.

14-3-3 Proteins↗
PubMed2003

A prospective randomized clinical trial to compare pre-coated and non-pre-coated brackets.

OBJECTIVE: To compare the clinical failure rate of pre-coated brackets and brackets bonded using Transbond XT light cure system OUTCOME MEASURES: (i) The clinical time required for bond up of upper and lower arches of both systems, (ii) bond failure rate for the first 6 months. DESIGN: Single centre randomized controlled clinical study. Thirty-three patients were bonded using a split mouth technique: randomly allocating the pre-coated brackets to upper left and lower right quadrants, and non-pre-coated brackets to the other quadrants. SETTING: Hospital Orthodontic Department, Basingstoke, Hampshire, UK. SUBJECTS: Orthodontic patients requiring fixed appliances. MAIN OUTCOME MEASURES: The site and time to bond failure was recorded for each bracket that failed over the first 6 months. The time required to bond upper and lower arches was measured using a stopwatch for each patient. RESULTS: t-Test for the difference of mean time needed to apply both groups of brackets, no significant difference (P > 0.2) was found. A chi-squared test for the difference in bracket failure between pre-coated (8.06%) and non-pre-coated (7.37%) showed no significant difference in bracket failure (P > 0.2). CONCLUSIONS: The clinical failure rate of pre-coated brackets is not significantly lower than conventional non-pre-coated brackets.

Bisphenol A-Glycidyl Methacrylate↗
PubMed2003

Upper gastrointestinal endoscopy performed by nurses: scope for the future?

BACKGROUND: Previous researchers have shown that non-medical endoscopists can perform lower gastrointestinal endoscopy as safely and effectively as medical staff. However, it is not known if upper gastrointestinal endoscopy performed by medical and non-medical endoscopists in clinical practice yields similar results in terms of performance, patient discomfort, and satisfaction. AIM: To determine differences in the yield of diagnosis for significant disease during upper gastrointestinal endoscopy performed by nurse and medical endoscopists and to measure patient discomfort, satisfaction, and attitudes towards future endoscopy. PATIENTS: This two part study included 3009 patients in a retrospective analysis and 480 in a prospective study. METHODS: The first part of the study assessed indications for endoscopy, diagnoses, and procedures performed by medical and nurse endoscopists. In a second prospective study, 480 patients were included to determine the association between endoscopist type and sedation, patient anxiety, discomfort, satisfaction, and attitudes towards future sedation. RESULTS: No patient refused endoscopy by either a nurse or medical endoscopist and there were no complications in either group. Nurses performed 1487 procedures and reported fewer endoscopies as "normal" than medical staff (p=0.006). Multivariate analysis showed that male sex, older age, inpatient status, dysphagia, and gastrointestinal bleeding, but not endoscopist type, were all associated with significant disease. In relation to discomfort and satisfaction, a similar proportion of patients received sedation in both groups (p=0.81). There were no differences in pre-procedure anxiety (p=0.61), discomfort during intubation (p=0.97), discomfort during examination (p=0.90), or post-procedure examination rating (p=0.79) in patients examined by medical or nurse endoscopists. CONCLUSION: Experienced nurses perform routine diagnostic gastroscopy safely in everyday clinical practice and with as little discomfort and as much patient satisfaction as medical staff.

Age Factors↗
PubMed2002

Effects of raloxifene on fracture severity in postmenopausal women with osteoporosis: results from the MORE study. Multiple Outcomes of Raloxifene Evaluation.

Raloxifene reduces the risk of new vertebral fractures, but its effect on the severity of these new fractures has not been determined. The MORE (Multiple Outcomes of Raloxifene Evaluation) trial studied the effects of placebo, raloxifene 60 or 120 mg/day in 7,705 postmenopausal women with osteoporosis. Radiologists assessed new vertebral fractures from radiographs and graded the fracture severity as normal (no fracture) or mild, moderate or severe. New clinical vertebral fractures were defined as new vertebral fractures associated with symptoms, such as back pain, and confirmed in radiographs. In the total study population, the majority (76.4%) of the women who experienced clinical vertebral fractures were diagnosed with new moderate/severe vertebral fractures. In turn, women with moderate/severe vertebral fractures in the overall population were more likely to experience clinical symptoms suggestive of fracture than were women who had new mild-only vertebral fractures. The incidence of new mild-only and moderate/severe fractures was the same in women without prevalent vertebral fractures, but the incidence of new moderate/severe fractures was 2 to 3 times higher than that for new mild-only fractures in women with prevalent vertebral fractures. Raloxifene 60 mg/day decreased the risk of at least 1 new moderate/severe vertebral fracture by 61% in women without prevalent vertebral fractures [RR 0.39 (95% CI 0.17, 0.69)], and by 37% in women with prevalent vertebral fractures [RR 0.63 (95% CI 0.49, 0.83)] at 3 years. The risk reductions for at least 1 new moderate/severe vertebral fracture were not significantly different between the raloxifene doses, in women with and without prevalent vertebral fractures. The effects of raloxifene on significantly decreasing the risk of new moderate/severe vertebral fractures may explain the risk reduction for new painful clinical vertebral fractures observed with raloxifene, and is particularly important in postmenopausal women with severe osteoporosis who are at higher risk for moderate or severe fractures.

Aged↗
PubMed2002

Importance of the superficial tissue layer for the indentation stiffness of articular cartilage.

Indentation testing is a widely used technique for nondestructive mechanical analysis of articular cartilage. Although cartilage shows an inhomogeneous, layered structure with anisotropic mechanical properties, most theoretical indentation models assume material homogeneity and isotropy. In the present study, quantitative polarized light microscopy (PLM) measurements from canine cartilage were utilized to characterize thickness and structure of the superficial, collageneous tissue layer as well as to reveal its relation to experimental indentation measurements. In addition to experimental analyses, a layered, transversely isotropic finite element (FE) model was developed and the effect of superficial (tangential) tissue layer with high elastic modulus in the direction parallel to articular surface on the indentation response was studied. The experimental indentation stiffness was positively correlated with the relative thickness of the superficial cartilage layer. Also the optical retardation, which reflects the degree of parallel organization of collagen fibrils as well as collagen content, was related to indentation stiffness. FE results indicated effective stiffening of articular cartilage under indentation due to high transverse modulus of the superficial layer. The present results suggest that indentation testing is an efficient technique for the characterization of the superficial degeneration of articular cartilage.

Animals↗
PubMed2002

Poly-L-glutamate, an anionic polymer, enhances transgene expression for plasmids delivered by intramuscular injection with in vivo electroporation.

Intramuscular (i.m.) injection of plasmids followed by electropermeabilization is an efficient process to deliver genes into skeletal myofibers that permits proteins to be produced and secreted at therapeutically relevant levels. To further improve skeletal muscle as a bioreactor, we identified a formulation that elevates transgene expression in myofibers after i.m. injection and electroporation. With secreted placental alkaline phosphate (SEAP) as reporter gene, plasmid formulated with poly-L-glutamate produced two- to eight-fold higher levels of SEAP in mouse serum than plasmid in saline. Various concentrations and molecular weights of poly-L-glutamate were similarly effective, but 6 mg/ml of 15-50 kDa poly-L-glutamate consistently yielded the highest expression levels. The poly-L-glutamate formulation was effective in two different muscle groups in mice at various plasmid doses for several transgenes, including an erythropoietin (EPO) gene, for which expression was elevated four- to 12-fold in comparison to animals that received EPO plasmid in saline. Transgene expression was localized to myofibers. Poly-L-glutamate may improve transgene expression in part by increasing plasmid retention in skeletal muscle. Poly-L-glutamate did not enhance gene transfer in the absence of electroporation. Therefore, the polymer is a novel formulation that specifically enhances the transfer and expression of genes delivered with electroporation.

Alkaline Phosphatase↗
PubMed2002

Topical photodynamic therapy in disseminated superficial actinic porokeratosis.

Photodynamic therapy (PDT) has been reported to be useful in treating certain nonmelanoma skin cancers and a variety of benign skin conditions. We examined whether PDT might be effective in the treatment of disseminated superficial actinic porokeratosis. Three patients with classical disseminated superficial actinic porokeratosis had a small test area treated with topical aminolaevulinic acid PDT. Following the first treatment, the disorder cleared in the test area in one patient, but failed to respond in the other two patients. After subsequent treatment, the initial benefit seen in the first patient was not sustained, and no response was seen in the second patient, while the third patient was not retreated due to hyperpigmentation induced by the procedure. The results obtained in this small case series suggest that topical PDT is not a promising treatment for disseminated superficial actinic porokeratosis.

Administration, Cutaneous↗
PubMed2002

Alpha-interferon 2a and 1 3-cis-retinoic acid for the treatment of metastatic renal cell carcinoma.

BACKGROUND: It is suggested that immunotherapy may have a better role than cytotoxic chemotherapy in the treatment of metastatic renal cell carcinoma. AIMS: A phase II study of alpha-interferon 2a (IFN2a) and 13-cis-retinoic acid (CRA) in the treatment of metastatic renal cell carcinoma. METHODS: Twenty-two patients with no previous systemic therapy were treated with IFN2a daily at 3 million units (MU) and escalated to 6 and 9 MU if tolerated, together with CRA given orally at 1 mg/kg per day in two divided doses. Changes in quality of life were also assessed. RESULTS: Twenty patients were available for assessment. Three patients (14%) achieved a partial response and five patients (23%) had stable disease. No patient achieved a complete response. A durable response was observed in partial responders with median length of response of 44 weeks (range 32-59 weeks). Therapy was stopped in seven (35%) patients due to treatment-related toxicities, and quality of life was worsened in the majority of patients. CONCLUSION: IFN2a and CRA has a low response rate and significant toxicity, and the combination as standard treatment of metastatic renal cell carcinoma is not recommended, despite the suggestion that CRA may lengthen the response to IFN2a.

Adult↗
PubMed2002

The influence of gender difference on the outcomes of infrainguinal bypass for critical limb ischaemia in Chinese patients.

PURPOSE: to investigate the influence of gender difference on the outcomes of infrainguinal bypass operations performed in Chinese patients with critical limb ischaemia. METHODS: we prospectively studied the results of 191 consecutive infrainguinal bypass operations (98 men, 93 women) for critical lower limb ischaemia in Chinese patients. RESULTS: the women were older than men (median 75 vs 70 years, p=0.001) and cigarette smoking was commoner in men (83% vs 37% p<0.001). The calibre of run-off arteries at the level of distal anastomosis was smaller in women (median 2.5 mm vs 2.0 mm, p=0.03). The 30-day mortality was 3% (five men vs one woman, p=0.09) and early graft failure occurred in 19 patients (12 women vs seven men, p=0.28). At 3 months limb loss occurred in 16 (10 women vs six men, p=0.35) patients. Survival (38% vs 60% at 4 years, p=0.12) was similar in men and women. However, women suffered from poorer primary (33% vs 49% at 3 years, p=0.03) secondary graft patency rates (35% vs 64% at 3 years, p=0.02) than men. Limb survival rate in two groups (75% vs 85% at 4 years, p=0.18) was comparable. CONCLUSION: following infrainguinal bypass for critical limb ischaemia, early results were similar in both gender groups. In the long-term, women patients suffered from significantly higher graft failure rate. However, their long-term survival and limb salvage rate remained comparable to those of men.

Adult↗
PubMed2002

Hepatolithiasis--a case series.

INTRODUCTION: Hepatolithiasis is an uncommon entity in Singapore. We reviewed the cases presented to our institution (a 1200-bedded restructured hospital) over a 5-year period. MATERIAL AND METHODS: Twelve cases of hepatolithiasis were treated between December 1995 and July 2000 representing 0.77% of gallstone disease operated on in the same period. The clinical presentation, investigations, treatment and subsequent progress are presented. RESULTS: The patients' ages ranged from 28 to 82 years. There was a male to female ratio of 5:7. All patients had upper abdominal pain at presentation; 10 patients had clinical evidence of cholangitis. Ultrasound was the commonest first line investigation but additional investigations, such as computed tomographic (CT) scan and various forms of cholangiography, were frequently necessary for complete delineation of the biliary disease. The intrahepatic stones were located predominantly in the left lobe of the liver. Parenchymal atrophy was seen in 83% of patients. Two patients underwent a biliary bypass operation only, 5 had a hepatic resection only, and 5 had combined procedures. Follow-up ranged from 4 to 50 months. Postoperative recovery was generally unremarkable. Complications included subphrenic abscess (1 patient), recurrent stricture (1 patient) and recurrent stones (1 patient). One patient had an elevated serum CA 19-9 preoperatively; a small villous adenoma was noted at the biliary stricture in the resected left lateral segment of the liver. There was no operative mortality. CONCLUSION: Hepatolithiasis is uncommon in Singapore. Complete diagnosis requires a combination of imaging modalities. Surgery remains the mainstay of definitive treatment. With adequate treatment, good outcome is possible.

Adult↗
PubMed2002

Hip pain and childhood malignancy.

In children, neuroblastoma can mimic various orthopaedic pathologies and this may create difficulties for doctors in reaching the correct diagnosis. Stage IV neuroblastoma was initially diagnosed as transient synovitis in this case report of a 7-year-old girl presenting with hip and low back pain.

Abdomen↗
PubMed2001

Hyper-expression of human apolipoprotein E4 in astroglia and neurons does not enhance amyloid deposition in transgenic mice.

Recent studies in mice have clearly demonstrated that eliminating Apo E alters the rate, character and distribution of A beta deposits. In the present study, we asked whether elevating the levels of Apo E can, in a dominant fashion, influence amyloid deposition. We expressed human (Hu) Apo E4 via the mouse prion protein promoter, resulting in high expression in both astrocytes and neurons; only astrocytes efficiently secreted Hu Apo E4 (at least 5-fold more than endogenous). Mice hyper-expressing Hu Apo E4 developed normally and lived normal lifespans. The co-expression of Hu Apo E4 with a mutant amyloid precursor protein (APP) (Mo/Hu APPswe) or mutant APP and mutant presenilin (PS1dE9) did not lead to proportional changes in the age of appearance, relative burden, character or distribution of A beta deposits. We suggest that these data are best explained by proposing that the mechanisms by which Apo E influences A beta deposition involves an aspect of its normal function that is not augmented by hyper-expression.

Amyloid beta-Peptides↗
PubMed2001

Oxazole yellow homodimer YOYO-1-labeled DNA: a fluorescent complex that can be used to assess structural changes in DNA following formation and cellular delivery of cationic lipid DNA complexes.

To improve transfection efficiency following delivery of plasmid expression vectors using lipid-based carriers, it is crucial to define structural characteristics of the lipid/DNA complexes that optimize transgene expression. Due to its strong affinity for DNA and high quantum yield, the fluorescent DNA intercalator YOYO-1 was used as a tool to assess changes in DNA that occur following lipid binding and cell delivery. In this study, the stability of the dye/DNA complex following binding of poly-L-lysine or monocationic lipids is characterized. More than 98% of the fluorescence measured for a defined DNA/YOYO-1 complex was lost when DNA was condensed using poly-L-lysine. This loss in fluorescence could be attributed to displacement of bound dye. In contrast, more than 30% of the fluorescence of the dye-labeled DNA was retained after formation of cationic lipid/DNA complexes. Significantly, the results illustrate differences in structural changes cationic lipids and PLL exert on plasmid DNA. The fluorescent lipid/DNA complex was used to assess DNA delivery to murine B16/BL6 cells in vitro. An assay relying on fluorescence resonance energy transfer between bound YOYO-1 and propidium iodide was used to distinguish between DNA attached to the cell surface and internalized DNA.

Benzoxazoles↗
PubMed2001

Developmental characteristics of epileptiform activity in immature rat neocortex: a comparison of four in vitro seizure models.

New-onset seizures and epilepsy have a relatively high incidence in infants and children. A leading hypothesis to explain an increased seizure susceptibility of the immature nervous system involves ontogenetic changes in different neurotransmitter systems, such as specific glutamate and GABA receptors. However, few studies have directly tested this hypothesis in a systematic fashion, especially in neocortical structures, where seizures in pediatric patients frequently arise. The present study investigated developmental changes in epileptiform activity in rat neocortical slices from four age groups (postnatal days P4--7, P13--16, P23--26, P41--47) due to four pharmacological conditions (4-aminopyridine, low magnesium, picrotoxin, CGP-35348) that differentially modulate glutamate and GABA systems. A characteristic age-dependence of the incidence of epileptiform activity was observed. In all pharmacological conditions, no epileptiform activity occurred in neocortical slices from P4--7 rats. Interictal discharges, ictal events, and spreading depression had a maximal incidence at P13--16 and decreased progressively in later age groups. 4-Aminopyridine, low magnesium, and picrotoxin induced all types of epileptiform activity with a similar age-dependent pattern, despite minor differences in quantitative characteristics of epileptiform activity between these three conditions. The GABA(B) antagonist, CGP-35348, did not elicit epileptiform activity in any age group, but could potentiate synaptic potentials. These findings establish that isolated neocortical tissue intrinsically displays ontogenetic changes in seizure susceptibility independent of systemic factors. The similar age-dependent patterns of epileptiform activity with multiple drugs support a concept of global developmental changes in excitability not specifically linked to any particular neurotransmitter system.

4-Aminopyridine↗