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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

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Characterization of a new member of the TNF family expressed on antigen presenting cells.

The TNF family is involved in the regulation of the immune system, and its members have been implicated in a variety of biological events such as apoptosis, cell proliferation, differentiation and survival. Here we present a new member of the TNF family, tumor necrosis factor superfamily member 20 (TNFSF20) that we have identified from the expressed sequence tag (EST) database and characterized. The human protein is a 285 amino acid long type II transmembrane protein and is 19% homologous to TNF in its extra-cellular domain. TNFSF20 is expressed at the surface of antigen presenting cells such as cells of the macrophagemonocyte lineage and dendritic cells. After treatment with bacterial lipopolysaccharide (LPS), TNFSF20 expression is downregulated at the surface of the expresssing cells, suggesting that the membrane-bound protein gets cleaved, and that a soluble factor is released in the extra-cellular compartment. The soluble form of the recombinant TNFSF20 induces proliferation of resting peripheral blood monocytes (PBMC) and cell death of activated lymphocytes. TNFSF20 might therefore play a critical role in the regulation of cell-mediated immune responses.

Amino Acid Sequence↗

Genetic analysis of adenovirus E1A: induction of genetic instability and altered cell morphologic and growth characteristics are segregatable functions.

Single multifunctional oncoproteins contribute to genomic instability development, but relationships between one or more oncoprotein-associated activities and genetic changes accompanying tumor cell progression are uncertain. Using NIH 3T3 derivative EN/NIH 2-20 containing transcriptionally silent neomycin phosphotransferase gene (neo) integrants with undetectable spontaneous reactivations, we studied wild-type (WT) and mutant adenovirus E1A-induced neo reactivation by neo-allelic rearrangement. WT E1A expression, yielding differential splice transcripts 12S and 13S and resulting in altered cell morphologic and growth characteristics, produced neo reactivations in 9 of 21 subclones (median rate per cell, 35 x 10(-6); range, 0.33 x 10(-6) to 936 x 10(-6)). Only 3 of 17 cell lines expressing CTdl976, a '12S' functional equivalent inducing altered cell morphologic and growth characteristics while lacking the 13S trans activation domain, yielded neo reactivations (range, 0.33 x 10(-6) to 0.67 x 10(-6)). One of 21 subclones expressing NTdl646, an E1A mutant retaining the trans domain but lacking p300 binding activity and the ability to alter cell morphologic and growth characteristics, produced neo reactivations (8.7 x 10(-6)). Other E1A mutants, all lacking the ability to alter cell morphologic and growth characteristics while binding pRb but variously lacking the trans domain and binding for p107 and/or p300, displayed undetectable neo-reactivations. 98 EN/NIH 2-20 derivatives coexpressing complementary mutant E1As exhibited altered morphologic and growth features, but only 10 of these produced neo reactivations, and maximum rates (14 x 10(-6)) were substantially lower than those in comparably derived, morphologically altered E1AWT-expressing counterparts (497 x 10(-6)). These findings suggest that maximum rates of gene reactivations by genomic rearrangement require the collective activities of functional domains assembled in single multifunctional proteins (or complexes) while altered cell morphologic and growth characteristics may arise through comparable sets of functional domains distributed across more than one protein (or complex).

3T3 Cells↗

Hemosiderosis with diabetes mellitus in untransfused Hemoglobin H disease.

A 37-year-old untransfused, non-drinking man with Hemoglobin H-CS disease presented with insulin-dependent diabetes mellitus, markedly elevated serum ferritin level, and marked iron deposition in hepatocytes. He did not carry either of the two common mutations of the HLA-H gene for hereditary hemochromatosis, namely, Cys282Tyr and His68Asp, nor did he have the associated HLA marker (HLA-A3, B7 nor B-14) for the disease. Patient with HbH disease should be monitored for iron overload.

Adult↗

Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome.

A novel missense mutation (codon 351, GCT (Ala) --> CCT (Pro)) of the FIX gene was characterised in a young female with mild hemophilia B. She is heterozygous for the FIX mutation inherited from her carrier mother. Analysis of the methyl-sensitive Hpa II sites at the 5' end of the hypoxanthine phosphoribosyltransferase gene showed that skewed inactivation of the X chromosome carrying her normal FIX gene accounted for the hemophilia phenotype.

Adult↗

Pharmacokinetics of three doses of epidural ropivacaine during hysterectomy and comparison with bupivacaine.

PURPOSE: Ropivacaine is a new long-acting aminoamide local anaesthetic, structurally related to bupivacaine. The clinical efficacy of 125 mg, 187.5 mg and 250 mg ropivacaine have been reported and compared with 125 mg bupivacaine for epidural analgesia during hysterectomy. In the pharmacokinetic part of this study the objectives were to 1) determine the dose proportionality in the pharmacokinetics of epidural ropivacaine, and 2) compare the pharmacokinetics of 125 mg ropivacaine and 125 mg bupivacaine. METHODS: In a randomized, double-blind controlled study, patients received one of four treatment regimens with ropivacaine (125, 187.5 or 250 mg) or bupivacaine (125 mg) as a 25 ml epidural bolus administered over three minutes. Peripheral venous blood samples were collected over 24 hr for ropivacaine or bupivacaine quantification using gas chromatography with nitrogen sensitive detection. Pharmacokinetic variables were derived from plasma concentration-time curve data. RESULTS: Fifty two women entered the study. Demographic characteristics were similar among groups. Six patients were excluded due to inadequate sensory block or an insufficient number of plasma samples. The peak plasma concentration (Cmax) of ropivacaine and the total area under the plasma concentration-time curve (AUC) increased proportionally with the dose. Apparent plasma clearance (CL) and the terminal half-life (t1/2) were similar in the three ropivacaine groups. When compared with the 125 mg ropivacaine group, the bupivacaine group had a longer terminal half life (P < 0.05). CONCLUSIONS: Epidural ropivacaine displays dose-proportional pharmacokinetic behaviour for doses of 125 mg to 250 mg. Ropivacaine has a shorter terminal half-life than bupivacaine.

Adult↗

Advances in regional anaesthesia and pain management.

Advances in regional anaesthesia to date have made it one of the safest modalities for surgical anaesthesia and pain management. Continued refinement and development of new block techniques and approaches enhance the potential for block success, rapid postoperative recovery and patient safety. This will benefit both patient care and the health care economy.

Amides↗

Sequence effect of irinotecan (CPT-11) and topoisomerase II inhibitors in vivo.

UNLABELLED: The DNA topoisomerases I and II are the target of several clinically important antineoplastic agents which produce DNA cleavage by stabilization of the covalent DNA-protein bond with resultant cell death after DNA synthesis is attempted. Depletion of the target topoisomerase and reciprocal changes in the other occur with drug treatment. PURPOSE AND METHODS: To develop empiric treatment regimens of combinations and sequences of agents directed against topoisomerase I (irinotecan/CPT-11) and II (etoposide and doxorubicin), in vivo studies were performed in mice bearing the EMT-6 mammary tumor to assess efficacy, host tolerance and the resultant biochemical changes in topoisomerase mRNA and protein. RESULTS: At 24 h after therapy, depletion of the target topoisomerase mRNA and protein with reciprocal increases in the alternate topoisomerase mRNA and, to a lesser extent, protein were noted. No therapeutic antagonism was found with any combination or sequence of agents, and therapeutic antagonism was noted with concurrent irinotecan/etoposide and sequential doxorubicin/irinotecan. Depletion of target topoisomerases by combined therapy beyond a threshold necessary for therapeutic efficacy produced no additional benefit. CONCLUSIONS: Antineoplastic therapy with combinations of topoisomerase I and II agents is feasible and may produce therapeutic synergy. The appropriate sequence may depend on the particular agents used. The rationale for such therapy, that topoisomerases I and II may have reciprocal and compensatory interactions, is supported by the biochemical data.

Animals↗

Molecular defects in Hb H hydrops fetalis.

The molecular defect in two unique cases of Hb H hydrops fetalis has been characterized. Both cases are due to co-inheritance of a 'non-deletion' defect affecting the alpha2 gene: at codon 30 delta GAG, Glu) and codon 59 (G --> A, Gly --> Asp) respectively, and a zeta-alpha thalassaemia (thal) 1 or alpha thal 1 genotype. These two non-deletion defects, unlike previously described cases, resulted in severe anaemia of the fetuses and emphasize the importance of performing prenatal diagnosis for these families.

Gene Deletion↗

The addition of continuous intravenous infusion of ketorolac to a patient-controlled analgetic morphine regime reduced postoperative myocardial ischemia in patients undergoing elective total hip or knee arthroplasty.

This double-blind randomized trial assessed the effect of adding an intravenous continuous infusion of ketorolac to a patient-controlled analgesia (PCA) morphine regimen on analgesia, heart rate, arterial blood pressure, and postoperative myocardial ischemia. Patients having elective total hip or knee replacement were randomized to receive ketorolac 30 mg bolus, followed by an infusion of 5 mg/h for 24 h or placebo. All patients had access to PCA morphine (20 microg/kg bolus, with a lockout of 6 min). Patients were monitored for pain visual analog scale, blood pressure, heart rate, and ST segment depression via a continuous Holter monitor. ST depression of 1 mm 60 ms after the J point was considered significant if it lasted more than 1 min. There was no difference in demographics, risk factors, or cardiac medications between the groups. Ketorolac-treated patients had significantly better pain control at 2, 6, and 24 h. There was significant morphine sparing at all times after 3 h. There was no difference in the number of ischemic events between the groups. The ischemic episodes of the patients who received ketorolac occurred at slower heart rates (97 +/- 15 vs 114 +/- 16 bpm, P = 0.001) than those of patients in the placebo group. The duration of ST depression was shorter in ketorolac-treated patients (24 +/- 35 vs 76 +/- 95 min, P < 0.05). All ST depressions were clinically silent. Logistic regression of factors predicting ischemia included the use of calcium channel blockers and low pain score. These results suggest that analgesia with ketorolac reduces the duration of ischemic episodes in the first 24 h postoperatively.

Aged↗