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Biomedical subjects

V Chan

Publications and source records attributed to V Chan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Population pharmacokinetics of lamotrigine.

The present study estimated the population pharmacokinetics of lamotrigine in patients receiving oral lamotrigine therapy with drug concentration monitoring, and determined intersubject and intrasubject variability. A total of 129 patients were analyzed from two clinical sites. Of these, 124 patients provided sparse data (198 concentration-time points); nine patients (four from a previous group plus five from the current group) provided rich data (431 points). The population analysis was conducted using P-PHARM (SIMED Scientific Software, Cedex, France), a nonlinear mixed-effect modeling program. A single exponential elimination model (first-order absorption) with heteroscedastic weighting was used. Apparent clearance (CL/F) and volume of distribution (V/F) were the pharmacokinetic parameters estimated. Covariate analysis was performed to determine which factors explained any of the variability associated with lamotrigine clearance. Population estimates of CL/F and V/F for lamotrigine generated in the final model were 2.14 +/- 0.81 L/h and 78.1 +/- 5.1 L/kg. Intersubject and intrasubject variability for clearance was 38% and 38%, respectively. The covariates of concomitant valproate and phenytoin therapy accounted for 42% of the intersubject variability of clearance. Age, gender, clinic site, and other concomitant antiepileptic drugs did not influence clearance. This study of the population pharmacokinetics of lamotrigine in patients using the drug clinically provides useful data and should lead to better dosage individualization for lamotrigine.

Adolescent↗
PubMed2001

Molecular genetic study of a childhood form of spinal muscular atrophy.

Molecular genetic studies were performed in 28 cases of childhood-onset spinal muscular atrophy (24 unrelated families). This consisted of type 1 (severe) (n = 5), type 2 (intermediate form) (n = 8), and type 3 (mild) (n = 15). Deletion of exons 7 and 8 of the SMNt gene was found in 100%, 100%, and 93%, respectively, in type 1, 2, and 3 spinal muscular atrophy. Deletion of exons 5 and 6 of the NAIP gene was found in 3 of 5 (60%) of type 1 and none of the type 2 and 3 cases. None of the 32 asymptomatic relatives had homozygous deletions in the SMNt and NAIP genes. Thus, the role of the NAIP gene needs to be specifically defined in spinal muscular atrophy. In a suspected case of spinal muscular atrophy, deletion of the SMNt gene is a useful laboratory marker for confirmation of the diagnosis.

Adolescent↗
PubMed2001

Using models in cardiovascular research: report on the satellite meeting to the International Congress of Physiological Sciences, Models in Cardiovascular Research.

Humans have used animals for centuries to understand their own biology. From September 2-4, 2001, scientists from around the world converged on Brisbane, in Australia, to discuss the use of animal models in cardiovascular research at a satellite meeting to the 34th International Congress of Physiological Sciences (August 26-September 1, 2001, Christchurch, New Zealand). The appropriateness of each model to the human disease was a major consideration. Other themes were the use of models to understand pathological processes, and to determine potential new targets for pharmacological intervention.

Animals↗
PubMed2000

Genetic and clinical features of hemoglobin H disease in Chinese patients.

BACKGROUND: Normally, one pair of each of the two alpha-globin genes, alpha1 and alpha2, resides on each copy of chromosome 16. In hemoglobin H disease, three of these four alpha-globin genes are affected by a deletion, a mutation, or both. We studied the alpha1-globin gene abnormalities and the clinical and hematologic features of Chinese patients with hemoglobin H disease in Hong Kong. METHODS: We assessed the clinical features, hematologic values, serum ferritin levels, and liver function of 114 patients with hemoglobin H disease. We also performed echocardiography and magnetic resonance imaging of the liver and examined the two pairs of alpha-globin genes. RESULTS: Hemoglobin H disease in 87 of the 114 patients (76 percent) was due to the deletion of three of the four alpha-globin genes (--/-alpha), a combination termed the deletional type of hemoglobin H. The remaining 27 patients (24 percent) had the nondeletional type of hemoglobin H disease, in which two alpha-globin genes are deleted and a third is mutated (--/alphaalphaT). All 87 patients with the deletional type of hemoglobin H were double heterozygotes in whom there was a deletion of both alpha-globin genes from one chromosome, plus a deletion of the alpha1 or alpha2 gene from the other chromosome (--/alpha- or --/-alpha). A variety of mutated alpha-globin genes was found in the patients with nondeletional type of hemoglobin H disease. Patients with the nondeletional type of the H disease had more symptoms at a younger age, more severe hemolytic anemia, and larger spleens and were more likely to require transfusions than patients with deletional hemoglobin H disease. The severity of iron overload was not related to the genotype. CONCLUSIONS: Chinese patients in Hong Kong with the nondeletional type of hemoglobin H disease have more severe disease than those with the deletional type of the disease. Iron overload is a major cause of disability in both forms of the disease.

Adolescent↗
PubMed2000

Exercise test in muscle channelopathies and other muscle disorders.

We studied the percentage change in compound muscle action potential (CMAP) amplitude and area during and after a 5-min maximal contraction of the muscle. The exercise test (ET) was performed on 64 patients with different muscle disorders and on 46 normal controls. The range of normal ET values was defined as the mean + 2 SD of the control values. The mean sensitivity of the test was 63% in the whole group with ion channel muscle disorders, the highest sensitivity being seen in primary periodic paralysis (81%) and the lowest in chloride channelopathies (17%). In thyrotoxic periodic paralysis, the ET was abnormal in the three of the four patients studied. In patients with myotonic dystrophy, a smaller than normal increase in CMAP amplitude occurred during and after exercise, whereas in proximal myotonic myopathy a normal initial increase in CMAP amplitude was followed by an abnormal decrement. We conclude that the ET can be of use in confirming abnormal muscle membrane excitability in patients with calcium and sodium channelopathies and thyrotoxic periodic paralysis. In chloride channelopathy, the test may also be abnormal, but shows no, or only a small, increase in amplitude or area in the immediate postexercise period. The test may also be abnormal in proximal myotonic myopathy, but is normal in myotonic dystrophy.

Action Potentials↗
PubMed2000

Bioelectronic detection of point mutations using discrimination of the H63D polymorphism of the Hfe gene as a model.

BACKGROUND: A bioelectronic detection platform has recently been developed that facilitates the detection and characterization of nucleic acids. The DNA chip platform is compatible with homogeneous assays because separate labeling and wash steps are not required. A one-step, bioelectronic detection assay was developed to genotype patient samples with respect to the H63D polymorphism of the Hfe gene, associated with hereditary hemochromatosis. METHODS AND RESULTS: Electrode arrays were modified with DNA capture probes that were perfectly matched to the wild-type or mutant allele of H63D. Amplicons containing the polymorphic site were hybridized with the capture probes on the electrode arrays in the presence of electronically labeled reporter (signaling) probes. Voltammetric analysis of the electrode arrays was conducted first at ambient temperature and then at elevated temperature. The electronic signal was preferentially diminished at elevated temperature from electrodes that hybridized with mismatched target amplicons. CONCLUSION: An assay for bioelectronic genotyping of the H63D polymorphism was developed and used with six patient specimens to show the feasibility of this system as a model for point mutation detection.

Amino Acid Substitution↗
PubMed2000

Consistent patterns of allelic loss in natural killer cell lymphoma.

Natural killer (NK) cell lymphomas are a group of rare but highly aggressive malignancies. Clinically, they can be divided into nasal NK cell lymphomas, nonnasal NK cell lymphomas, and aggressive NK cell lymphoma/leukemia. To determine the patterns of genetic deletions in these tumors, we performed loss of heterozygosity (LOH) analysis on 15 cases (11 nasal and four nonnasal), and fluorescence in situ hybridization on three cases of aggressive lymphoma/leukemia. A panel of 41 microsatellite loci on chromosomes 6q, 11q, 13q, and 17p were investigated. LOH at chromosomes 6q and 13q was frequently detected in NK cell lymphomas, being found in 80 and 66.7% of cases, respectively. LOH at chromosomes 11q and 17p was less common, being found in 28.6 and 30.8% of cases, respectively. Most tumors showed multiple loci deletions at different chromosomal regions, but several patterns of LOH could be defined. LOH at chromosome 6q was found in 90.9% of nasal NK cell lymphomas, but only in 50% of nonnasal NK cell lymphomas. LOH at chromosome 13q was found in 63.6% of nasal NK cell lymphomas and 75% of nonnasal NK cell lymphomas. For nasal NK cell lymphomas, LOH at 13q was found in 33.3% of cases at presentation, but 100% of cases at relapse. Five tumors showed LOH in only one chromosomal region, involving 6q in three cases (two nasal and one nonnasal), and 13q in two cases (both nonnasal). For the three cases of aggressive NK cell lymphoma/leukemia studied by fluorescence in situ hybridization, DNA loss at 13q14 and 17p13 regions were demonstrated. 17p13 seemed to be more commonly involved in aggressive than nasal and nonnasal NK cell lymphomas. Our results suggested that consistent patterns of LOH could be defined in NK cell malignancies. These deleted loci may contain genes important in the initiation and progression of this lymphoma.

Adult↗
PubMed2000

Single nucleotide polymorphisms of the factor IX gene for linkage analysis in the southern Chinese population.

Carrier detection and prenatal testing for haemophilia B in Oriental populations have been hampered by the lack of informative markers within the factor IX (FIX) gene. We detected a T/C nucleotide variation at nucleotide 32770 in the poly-A region of the FIX gene in the mother of a haemophilia B child. Analysis of 139 unrelated alleles revealed a heterozygosity rate of 0.193, thus offering an additional marker for linkage analysis. Together with two other polymorphic sites (5' MseI and 3' HhaI) found in Chinese and Thai populations, these polymorphisms were useful in 66% of the families studied.

China↗
PubMed2000

Ten years' experience of antenatal mean corpuscular volume screening and prenatal diagnosis for thalassaemias in Hong Kong.

OBJECTIVE: To determine the prevalence of thalassaemia carriers in Hong Kong. SUBJECTS AND METHODS: From 1988 to 1997, 25,834 (53.7%) of 48,089 mothers were screened for thalassaemias by mean corpuscular volume (MCV) at the first antenatal visit. RESULTS: In the screened population of 25,834, 2229 (8.6%) had MCV < or = 75 fl. Of these, 1121 (4.3%) were alpha-thal, 715 (2.8%) were beta-thal, 23 (0.1%) were alpha beta-thal, 57 (0.2%) were other haemoglobin variants, and 281 (1.1%) had either iron deficiency or uncertain causes. Out of 200 pregnancies at risk for homozygous alpha-thal-1 and 32 at risk for beta-thal major, 27 homozygous alpha-thal-1 and 7 beta-thal major were identified, compared favourably with the expected figures of 23 and 9. CONCLUSION: Antenatal screening for thalassaemias by MCV is simple, effective and reliable. Universal screening has a different impact as bone marrow or cord blood stem cell transplant provides cure for beta-thal major. At risk couples have, as an alternative to termination of pregnancy, the option of early detection and treatment for their affected newborns or fetuses.

China↗
PubMed2000

A review of Hib epidemiology in Asia.

Meningitis due to an invasive Haemophilus influenzae type b (Hib) infection, has been previously perceived to be relatively uncommon in Asia. However, the incidence of disease and its impact may have been underestimated. In addition to a lack of microbiological facilities in some hospitals, difficulties in culturing the organism and the widespread use of antibiotics may have hidden the true incidence of the disease in some countries. Furthermore, the reported disease burden probably underestimates the incidence of Hib pneumonia. The epidemiology of invasive Hib disease for various Asian nations is reviewed in this paper. Hospital-based studies show that Hib is a major cause of bacterial meningitis and/or pneumonia in the Philippines, India, Thailand, Malaysia, Indonesia and Vietnam. Singapore and Hong Kong have a low incidence of infection compared with Western and other Asian nations. This low incidence is not due to a higher level of natural protective antibodies, but may be related to an interaction between environmental and genetic factors. Therefore the widespread belief that Hib infection is unimportant in Asia does not refer to Asia as a whole and possibly to Chinese patients only, and failure to recognize this has serious implications. The inclusion of Hib vaccine in the routine infant immunization schedule in many industrialized nations has significantly reduced the incidence of invasive disease. Recent studies have shown Hib vaccination is also effective in preventing invasive disease in children in developing countries. While population-based data may be required to confirm the need for public-funded infant Hib immunization in Asia, its introduction in countries with a high incidence of Hib meningitis and/or pneumonia has the potential to significantly improve pediatric health and survival.

Asia↗
PubMed1999

Femoral nerve block and ketorolac in patients undergoing anterior cruciate ligament reconstruction.

PURPOSE: The primary objective was to evaluate the analgesic effectiveness of femoral nerve block and ketorolac following ACL reconstruction. The secondary objective was to examine their effects on recovery milestones. METHODS: Prior to standard general anesthesia, 90 patients were randomized into three groups of preoperative treatment: 1) femoral nerve block (15 mL bupivacaine 0.5%) and 1 mL normal saline i.v. (FNB group); 2) placebo femoral nerve block (15 mL normal saline) and 30 mg (1 mL) ketorolac i.v. (KT group); 3) placebo femoral nerve block (15 mL normal saline) and 1 mL normal saline i.v. (PL group). Postoperatively, pain was assessed by visual analogue score, demand and consumption of morphine via patient-controlled analgesia pump. The times for patients to tolerate oral fluid, food, sit up, ambulate and void were also noted. RESULTS: Morphine consumption within one hour, three hours and until POD 1 in the FNB group was lower than the PL group (7 +/- 6, 11 +/- 9, 27 +/- 23 mg vs 13 +/- 5, 20 +/- 9, 49 +/- 28 mg respectively), whereas only that within one hour in the KT group was lower than the PL group. Pain score was lower in FNB and KT groups in the first postoperative hour than in the PL group (P < 0.05). There were no differences among the three groups in the times to meet recovery milestone and discharge criteria. CONCLUSION: Femoral nerve block provides superior analgesia than placebo for ACL reconstruction but was insufficient to facilitate early recovery.

Adolescent↗
PubMed1999

A multicentre trial of ropivacaine 7.5 mg x ml(-1) vs bupivacaine 5 mg x ml(-1) for supra clavicular brachial plexus anesthesia.

PURPOSE: To compare the efficacy of ropivacaine 7.5 mg x ml(-1) with bupivacaine 5.0 mg x ml(-1) for subclavian perivascular brachial plexus block. METHODS: After informed consent, 104 ASA I-III adults participated in a randomized, double-blind, multi-center trial to receive 30 ml of either ropivacaine 7.5 mg x ml(-1) or bupivacaine 5.0 mg x ml(-1) for subclavian perivascular brachial plexus block prior to upper limb surgery. Onset and duration of sensory and motor block in the distribution of the axillary, median, musculo-cutaneous, radial and ulnar nerves were assessed. RESULTS: Onset times and duration of sensory and motor block were similar between groups. Mean duration of analgesia for the five nerves was between 11.3 and 14.3 hr with ropivacaine and between 10.3 and 17.1 hr with bupivacaine. Quality of muscle relaxation judged as excellent by the investigators was not significantly different (ropivacaine - 35/49, bupivacaine - 30/49). The median time to first request for analgesia was comparable between the two groups (11-12 hr). One patient developed a grand mal seizure shortly after receiving bupivacaine and recovered consciousness within 30 min. There were no serious adverse events in the ropivacaine group. CONCLUSIONS: Thirty ml ropivacaine 7.5 mg x ml(-1) (225 mg) produced effective and well tolerated brachial plexus block of long duration by the subclavian perivascular route. In this study, the results were similar to those of 30 ml bupivacaine 5.0 mg x ml(-1).

Adolescent↗
PubMed1999

Qualitative and quantitative magnetic resonance imaging in haemoglobin H disease: screening for iron overload.

OBJECTIVES: To evaluate the clinical utility of magnetic resonance imaging (MRI) in screening for iron overload in non-transfusion dependent Haemoglobin (Hb) H disease. PATIENTS AND METHODS: Thirty-six non-transfusion dependent HbH patients were evaluated with axial spin echo T1 and gradient echo T2 MRI of the abdomen and heart. The ratios of signal intensities (SIR) of the liver, spleen, pancreas and heart to paraspinous muscles were calculated. SIR <1 was taken as indicative of iron overload. Qualitative grading (0-4 scale) of iron overload was also performed. The relationship between T1 and T2 SIR and serum ferritin, and that between qualitative grading and serum ferritin were examined using standard statistical methods. Comparisons were also made between qualitative grading and quantitative T1 and T2 SIR data in diagnosing iron overload. Six patients underwent liver biopsies. RESULTS: T2 SIR was more sensitive in detecting iron overload than T1 SIR. Thirty-three livers, 13 spleens, six pancreas and one heart were diagnosed as having iron overload with T2 SIR, including three patients with normal serum ferritin. A positive diagnosis by T2 SIR was more closely related to that of qualitative grading than T1 SIR. Serum ferritin was negatively correlated with hepatic SIR (T1 and T2), and with T2 SIR of the spleen and pancreas, even after adjustment for age. Liver haemosiderosis was confirmed in all six patients who underwent liver biopsies. Liver iron concentration of only one and a half times the normal was found in one patient with positive MR findings. CONCLUSION: MR is a non-invasive, effective method for early detection of iron overload particularly in the liver and spleen. Qualitative grading and quantitative T2 SIR data are equivalent in diagnosing iron overload. Routine screening of non-transfusion dependent HbH patients will identify high risk patients in whom early therapeutic intervention may prevent further complications and morbidity.

Adult↗
PubMed1999

A reverse dot-blot method for rapid detection of non-deletion alpha thalassaemia.

A reverse dot blot method based on membrane-bound allele-specific oligonucleotides as hybridization targets for amplified alpha-gene fragments has been developed for the rapid detection of four non-deletion alpha thalassaemia defects found in the Chinese. Since these non-deletion defects account for 22 8% of haemoglobin H disease, a sensitive, specific and rapid screening method should be of value.

Humans↗
PubMed1999

Sameridine is safe and effective for spinal anesthesia: a comparative dose-ranging study with lidocaine for inguinal hernia repair.

UNLABELLED: Sameridine is a new compound with local anesthetic and analgesic properties when injected intrathecally. We studied the anesthetic and analgesic efficacy of three doses of isobaric sameridine (15, 20, and 23 mg) compared with 100 mg of hyperbaric lidocaine for spinal anesthesia in 140 healthy male patients undergoing inguinal hernia repair. Patients received spinal anesthesia with 4 mL of the study drug injected at the L2-3 or L3-4 interspace in the lateral decubitus position. All three doses of sameridine provided spinal anesthesia similar to lidocaine, with a slightly longer time to reach peak block height. The failure rate was highest in the 15-mg sameridine group, and accrual was discontinued in that group after 35 patients. The duration of blockade was shorter with lidocaine, but the time to voiding and ambulation was similar in all groups. Patients receiving sameridine were less likely to request morphine for postoperative analgesia and were less likely to request any analgesia in the first 4 h after injection of the drug. Use of oral analgesics (hydrocodone and acetaminophen) was similar in all groups after the first 4 h of the 24-h observation. We conclude that, in the three doses studied, sameridine provided spinal anesthesia similar to lidocaine, but with residual analgesia after drug injection that reduced the need for systemic analgesics in the first 4 h postoperatively. IMPLICATIONS: In this clinical trial, we show the potential efficacy of a class of drugs that can produce both spinal anesthesia and postoperative analgesia when used for hernia repair.

Adolescent↗
PubMed1999

Adverse cardiac outcomes after noncardiac surgery in patients with prior percutaneous transluminal coronary angioplasty.

UNLABELLED: In this retrospective cohort study, we compared adverse cardiac outcomes after noncardiac surgery among patients with prior percutaneous transluminal coronary angioplasty (PTCA), patients with nonrevascularized coronary artery disease (CAD), and normal controls. Inpatient hospital discharge abstracts from all nonfederal acute care hospitals in Washington State linked to death certificates were evaluated. Patients > or =45 yr old with prior PTCA who underwent noncardiac surgery from 1987 to 1993 were matched by age, sex, surgery type, and discharge year to 686 patients with CAD and to 2155 normal controls (no CAD). We compared risk for adverse cardiac outcomes (death, myocardial infarction, angina, congestive heart failure, malignant dysrhythmia, cardiogenic shock, coronary artery bypass graft, or PTCA) within 30 days. Patients with PTCA had twice the risk of adverse cardiac outcome as normal controls (odds ratio [OR] 1.98; P < 0.001), with a higher risk of angina (OR 7.84), congestive heart failure (OR 2.06), and myocardial infarction (OR 3.86) but a lower risk of death (OR 0.46; P < 0.001). Patients with PTCA had half the risk of adverse cardiac outcome as patients with CAD (OR 0.50; P < 0.001), including less risk of angina (OR 0.51) and congestive heart failure (OR 0.40; P < 0.001), but no difference in myocardial infarction (P = 0.304) or death (P = 0.436). No difference was found between 142 patients with recent PTCA (< or =90 days before noncardiac surgery) matched to patients with CAD (OR 0.90; P = 0.396). Patients revascularized by PTCA >90 days before noncardiac surgery seem to have a lower risk of poor outcome than nonrevascularized patients, although not as low as normal controls. For recent PTCA patients, the lack of difference compared with CAD patient outcomes requires a larger sample size for verification. Present findings do not lend support to a role for prophylactic PTCA to improve noncardiac surgery outcomes. This investigation did not control for CAD severity, medical management, or comorbidities. Study of these factors is needed before the clinical implications of PTCA for noncardiac surgical risk can be completely assessed. IMPLICATIONS: Hospital records showed patients with prior percutaneous transluminal coronary angioplasty were twice as likely as healthy patients to have an adverse cardiac outcome after noncardiac surgery, although their risk was reduced by half compared with patients with untreated coronary artery disease. Further study of the role of percutaneous transluminal coronary angioplasty in modulating noncardiac surgery risk is needed.

Aged↗
PubMed1999

Comparison of the intubation conditions provided by rapacuronium (ORG 9487) or succinylcholine in humans during anesthesia with fentanyl and propofol.

BACKGROUND: Currently, the only approved muscle relaxant with a rapid onset and short duration of action is succinylcholine, a drug with some undesirable effects. Rapacuronium is an investigational nondepolarizing relaxant that also has a rapid onset and short duration and consequently should be compared with succinylcholine in its ability to facilitate rapid tracheal intubation. METHODS: This prospective, randomized clinical trial involved 336 patients. Anesthesia was induced with fentanyl and propofol and either 1.5 mg/kg rapacuronium or 1.0 mg/kg succinylcholine. The goal was to accomplish tracheal intubation by 60 s after administration of the neuromuscular blocking drug. Endotracheal intubation was performed, and conditions were graded by a blinded investigator. Recovery of neuromuscular function was assessed by electromyography. RESULTS: Intubation conditions were evaluated in 236 patients. Intubation by 60 s after drug administration occurred in 100% of patients with rapacuronium and in 98% with succinylcholine. Intubation conditions were excellent or good in 87% of patients with rapacuronium and in 95% with succinylcholine (P < 0.05). The time (median and range) to the first recovery of the train-of-four response was 8.0 (2.8-20.0) min with rapacuronium and 5.7 (1.8-17.7) min with succinylcholine (P < 0.05). The overall incidence of adverse effects was similar with both drugs. CONCLUSIONS: A 1.5-mg/kg dose of rapacuronium effectively facilitates rapid tracheal intubation. It can be considered a valid alternative to 1.0 mg/kg succinylcholine for this purpose.

Adolescent↗