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Biomedical subjects

V W Chan

Publications and source records attributed to V W Chan.

At least 19 recordsLinked to original sources
PubMed2001

Pharmacokinetic profile of epidurally administered methylnaltrexone, a novel peripheral opioid antagonist in a rabbit model.

Methylnaltrexone (MNTX) is the first peripheral opioid receptor antagonist used in man to treat acute and chronic opiate-mediated side-effects. We describe in a rabbit model the pharmacokinetics of epidurally administered MNTX 0.66 mg kg(-1), and we tested the hypothesis that epidurally administered MNTX does not penetrate the dura into the subarachnoid space. There were minimal concentrations of MNTX (40 ng ml(-1)) detected in the CSF at 10 and 20 min and none thereafter in comparison with the high serum levels. The serum drug concentration-time profile fitted a two-compartment pharmacokinetic model. Further studies are warranted as epidurally administered MNTX may have the potential to reverse epidural opioid-mediated side-effects whilst preserving analgesia.

Animals↗
PubMed2000

Mutational analysis of BRCA1 and BRCA2 genes in Chinese ovarian cancer identifies 6 novel germline mutations.

Germline mutations in the BRCA1 and BRCA2 genes predispose women to breast and ovarian cancer. An incidence of 5% and 3.3% respectively has been reported of BRCA1 and BRCA2 mutations in women with ovarian cancer unselected for family history. The contribution of BRCA1 and BRCA2 mutations to ovarian cancer in Chinese women is unknown. A total of 60 samples of ovarian cancer diagnosed in Chinese unselected for age or family history were analyzed for BRCA mutations using the protein truncation test. The entire coding exon of BRCA1 of 53 cases and that of exon 11 of BRCA2 of 43 cases were successfully screened. Six germline (11.3%) mutations (633C>T, 1080delT, 1129delA, 2371-2372delTG, 3976-3979delGTGA, and IVS 22+7 A>G) were detected in BRCA1. One germline mutation (3337C>T) (2.1%) was detected in BRCA2. None of these seven cases were associated with strong family history of breast and/or ovarian cancer. Five out of our six BRCA1 mutations and the one BRCA2 mutation identified are novel. Our 11.3% incidence of BRCA1 mutations in ovarian cancer found amongst Chinese with insignificant family history is apparently higher than that previously reported in other populations. It suggests that BRCA1 mutation may play a significant role in the development of sporadic ovarian cancer in Chinese women.

Adult↗
PubMed2000

Novel analgesic adjuncts for brachial plexus block: a systematic review.

This article reviews current evidence for the efficacy of adding novel analgesic adjuncts to brachial plexus block, the goal of which is to prolong analgesic effect without the disadvantage of systemic side effects or prolonged motor block. It may also allow for a reduction in the total dose of local anesthetic used. Novel adjuncts studied to date include opioids, clonidine, neostigmine, and tramadol. Twenty-four studies were reviewed and assessed by using specific inclusion criteria, and only those studies satisfying these criteria were included in the final assessment. Satisfactory studies were then assessed for inclusion of a systemic control group to determine peripheral effect, as opposed to possible systemic effect, of an adjunct administered peripherally. Evidence regarding the analgesic benefit of opioid adjuncts remains equivocal and more evidence is required before their routine use can be recommended. Clonidine appears to have significant analgesic benefit and to cause minimal adverse effects when used in doses up to 150 microg. Data regarding other drugs, such as tramadol and neostigmine, are not sufficient to allow for any recommendations, and further studies are required.

Adult↗
PubMed2000

Determining minimum effective anesthetic concentration of hyperbaric bupivacaine for spinal anesthesia.

We determined the minimum effective anesthetic concentration (MEAC) of bupivacaine for spinal anesthesia, defined as the median effective concentration at which a spinal anesthetic produces surgically equivalent anesthesia within 20 min of administration in 50% of human subjects. Two doses of spinal bupivacaine (7.5 mg and 10 mg) were administered to 45 volunteers (19-39 yr) in a randomized, double-blinded fashion. Hyperbaric bupivacaine solutions of 0.1% to 0.75% containing 8.25% dextrose were administered intrathecally and MEAC established by using the Dixon's up-and-down method. Complete anesthesia was defined as: 1) pinprick anesthesia at or higher than T12; 2) anesthesia to transcutaneous tetanic electric stimulation (50 Hz at 60 mA for 5 s) in the knees; and 3) complete leg paralysis, all occurring in both lower extremities within 20 min of intrathecal injection. We found that the MEAC of spinal bupivacaine was 0.43% (95% confidence interval 0.24-0.62) when 10 mg was administered. At this dose, a concentration as low as 0.1% could provide complete anesthesia, but consistent blockade was obtained only with the 0.7% solution. The 7.5-mg dose failed to provide complete anesthesia consistently, even in the presence of 0.75% (maximum). The current commercially available 0.75% concentration of hyperbaric bupivacaine seems to be clinically optimal when 10 mg is used if complete bilateral lower extremity blockade is desired.

Adult↗
PubMed1999

Somatic mutations in the BRCA1 gene in Chinese sporadic breast and ovarian cancer.

Inherited mutations in the BRCA1 gene confer increased susceptibility to breast and ovarian cancer. Its role in sporadic carcinogenesis is not well defined. Somatic mutations in breast cancers have not been reported and to date there are only three reports of somatic mutations in sporadic ovarian cancers. To investigate the contribution of BRCA1 mutations to sporadic breast and ovarian cancer in the Chinese population, we analysed 62 samples from Chinese women using the protein truncation test. There were 40 cases of breast cancer under age 50 and 22 cases of ovarian cancer, all unselected for family history. There was no age selection for the ovarian cancers. We found two somatic BRCA1 mutations in exon 11, one in a breast cancer and the other in an ovarian cancer, both of which result in truncated proteins. Our results indicate that somatic BRCA1 mutations, like somatic mutations in the BRCA2 gene, though very rare, can be found in both breast and ovarian cancers and support a tumor suppressor function for BRCA1 in sporadic tumors.

Adult↗
PubMed1999

Secondary lymphoid-tissue chemokine (SLC) is chemotactic for mature dendritic cells.

Dendritic cells (DC) take up antigen from the periphery and migrate to the lymphoid organs where they present the processed antigens to T cells. The propensity of DC to migrate changes during DC maturation and is probably dependent on alterations in the expression of chemokine receptors on the surface of DC. Secondary lymphoid tissue chemokine (SLC), a recently discovered chemokine for naïve T cells, is primarily expressed in secondary lymphoid organs and may be important for colocalizing T cells with other cell types important for T-cell activation. We show here that SLC is a potent chemokine for mature DC but does not act on immature DC. SLC also induced calcium mobilization specifically in mature DC. SLC and Epstein-Barr virus-induced molecule 1 ligand chemokine completely cross-desensitized the calcium response of each other, indicating that they share similar signaling pathways in DC. The finding that SLC is a potent chemokine for DC as well as naïve T cells suggests that it plays a role in colocalizing these two cell types leading to cognate T-cell activation.

Cells, Cultured↗
PubMed1999

Local and regional block in postoperative pain control.

Local and regional block provides an effective means for the control of postoperative pain. In surgery involving the trunk, it serves as a useful alternative to epidural analgesia. With the increasing use of low molecular weight heparin, the use of peripheral nerve block is increasingly popular for patients undergoing lower limb surgery.

Anesthetics, Local↗
PubMed1999

Respiratory effects of low-dose bupivacaine interscalene block.

In this double-blind study, interscalene brachial plexus (ISBP) block was performed in 11 volunteers using 10 ml of either 0.25% (n = 6) or 0.5% (n = 5) bupivacaine with epinephrine 1:200,000. Diaphragmatic excursion, respiratory function and neural function were assessed for 90 min. Our results showed that hemidiaphragmatic excursion declined significantly after block in the 0.5% group and paradoxical movement during inspiration was more common than in the 0.25% group. Forced vital capacity and forced expiratory volume in 1 s declined significantly in the 0.5% group (mean 74.6 (SD 13.0)% and 78.2 (19.9)% of baseline, respectively) but not in the 0.25% group. Sensory anaesthesia in the upper limb was found consistently in both groups, although biceps paralysis occurred earlier after 0.5% bupivacaine. We conclude that ISBP block using 10 ml of 0.25% bupivacaine provided upper limb anaesthesia to pinprick in C5-6 dermatomes with only occasional interference with respiratory function.

Adult↗
PubMed1999

The impact of saline flush of the epidural catheter on resolution of epidural anesthesia in volunteers: a dose-response study.

UNLABELLED: We evaluated the effect of 1, 20, and 40 mL of epidural saline flush on recovery from lidocaine epidural anesthesia. Eight volunteers were studied for three study periods, each separated by 72 h. The volume of saline was randomized, and a new catheter was inserted for each study period. A standardized dose of 20 mL of 2% plain lidocaine was injected for 10 min, followed by an epidural saline flush 30 min later. Sensory block was assessed by pinprick and transcutaneous electrical stimulation and motor block by a modified Bromage scale and isometric maximal force contraction. Times to void and ambulate independently before discharge were recorded. Peak plasma lidocaine concentrations and time to peak concentration were determined. Results from six volunteers showed that epidural saline, 40 mL, significantly altered anesthetic resolution, accelerating the time of complete sensory and motor block regression (P < 0.05). Median peak levels of sensory and motor block and times to void and ambulate were similar among treatment groups. Peak plasma lidocaine concentrations were similar in all treatment groups. Our data suggest that a 40-mL epidural saline injection 30 min after the induction facilitates regression of epidural lidocaine anesthesia, but a 20-mL bolus does not. Epidural saline injection does not affect vascular absorption of epidural lidocaine. IMPLICATIONS: Epidural catheter flushing with 40 mL of saline, after establishment of epidural lidocaine anesthesia, can facilitate sensory and motor block recovery. However, this does not affect vascular absorption of epidural lidocaine.

Absorption↗
PubMed1999

Quantitative comparison of leakage under the tourniquet in forearm versus conventional intravenous regional anesthesia.

UNLABELLED: We compared the quantitative leakage between forearm and conventional IV regional anesthesia (IVRA). Forearm IVRA remains unpopular because of the theoretical risk of local anesthetic leakage through the interosseous vessels. IVRA was simulated on the forearm or arm during two separate, randomized sessions using a double tourniquet in 14 volunteers. A radiolabeled substance, DISIDA (99m Tc-disofenin) with a structure similar to lidocaine, was injected instead of local anesthetic. Volumes of 0.4 mL/kg (maximum 25 mL), were used for forearm IVRA and 0.6 mL/kg (maximum 45 mL) for conventional IVRA. A gamma camera recorded radioactivity levels in the limb distal to the tourniquet every 30 s while the tourniquet was inflated (25 min) and for 20 min postdeflation. The leakage of radiolabeled substance during inflation was similar in both groups, 6%+/-12% (mean +/- SD) from the forearm and 10%+/-20% from the upper arm. After deflation, mean loss of radioactivity was higher in conventional IVRA, 70%+/-7% vs 57%+/-11% and 82%+/-5% vs 69%+/-11% at 3 and 20 min, respectively (P < 0.001). We conclude that forearm IVRA results in tourniquet leakage comparable to conventional IVRA and is potentially safer because the required dose of local anesthetic is smaller. IMPLICATIONS: Using a tourniquet on the forearm for IV regional anesthesia does not increase the risk of drug leakage. This is potentially a safer technique compared with conventional IV regional anesthesia because a much smaller dose of local anesthetic is required.

Adult↗
PubMed1999

Comparison of ropivacaine and lidocaine for intravenous regional anesthesia in volunteers: a preliminary study on anesthetic efficacy and blood level.

BACKGROUND: Ropivacaine may be useful for intravenous regional anesthesia, but its anesthetic effectiveness and toxicity have not been evaluated. METHODS: Two doses of ropivacaine (1.2 and 1.8 mg/kg) and one dose of lidocaine (3 mg/kg) were compared for intravenous regional anesthesia in 15 volunteers. An arm tourniquet was inflated for 30 min after injection and then deflated in two cycles. Sensory block was measured by response to touch, cold, pinprick, and transcutaneous electric stimulation, and motor function was measured by hand grip strength and muscle power. Median, ulnar, radial, and musculocutaneous nerve functions were tested before local anesthetic injection and then at 5-min intervals until blocks resolved. The plasma ropivacaine and lidocaine concentrations were determined from arterial and venous blood samples drawn from the unanesthetized arm. RESULTS: Sensory and motor blocks were complete within 25 min and 30 min, respectively, in all three treatment groups. However, recovery of sensory and motor block after tourniquet release was slowest in the high-dose ropivacaine group. Anesthesia to pinprick and transcutaneous electric stimulation was sustained in all the volunteers in the high-dose ropivacaine group for 55 min and 85 min, respectively, whereas complete recovery was observed in the lidocaine group (P = 0.008) and partial recovery in the low-dose ropivacaine group (P < 0.05) during the same period. Motor block also was sustained in the high-dose ropivacaine group for 70 min, which was significantly longer than in the lidocaine group (P < 0.05). All volunteers (five of five) given lidocaine and one volunteer given high-dose ropivacaine reported light-headedness and hearing disturbance during tourniquet release when the arterial plasma lidocaine and ropivacaine concentrations were 4.7+/-2.1 microg/ml (mean) and 2.7 micro/ml, respectively. CONCLUSION: Compared with lidocaine, intravenous regional anesthesia with ropivacaine appears to be comparable but has longer-lasting residual anesthesia.

Adult↗
PubMed1998

The molecular mechanism of B cell activation by toll-like receptor protein RP-105.

The B cell-specific transmembrane protein RP-105 belongs to the family of Drosophila toll-like proteins which are likely to trigger innate immune responses in mice and man. Here we demonstrate that the Src-family protein tyrosine kinase Lyn, protein kinase C beta I/II (PKCbetaI/II), and Erk2-specific mitogen-activated protein (MAP) kinase kinase (MEK) are essential and probably functionally connected elements of the RP-105-mediated signaling cascade in B cells. We also find that negative regulation of RP-105-mediated activation of MAP kinases by membrane immunoglobulin may account for the phenomenon of antigen receptor-mediated arrest of RP-105-mediated B cell proliferation.

Animals↗
PubMed1998

Defective negative regulation of antigen receptor signaling in Lyn-deficient B lymphocytes.

BACKGROUND: To elucidate the role of the Src family kinase Lyn in B cell receptor (BCR) signaling, we and others previously generated lyn-/- mice and analyzed their B cell responses. Although the initiation of BCR signaling in lyn-/- B cells is delayed, BCR-induced ERK2 activation and proliferation are enhanced. As the co-receptors Fc gamma RIIb1 and CD22 have been shown to be negative regulators of BCR signaling, we have now examined their functional roles in lyn-/- B cells. RESULTS: B cells from lyn-/- mice have increased expression of the protein product of the early response gene egr-1, enhanced activation of Jun N-terminal kinase (JNK), and elevated calcium responses upon BCR cross-linking. Tyrosine phosphorylation of Fc gamma RIIb1 in lyn-/- B cells was reduced but negative regulation of the BCR signal by Fc gamma RIIb1 was only modestly impaired. In contrast, tyrosine phosphorylation of CD22 was greatly decreased in lyn-/- B cells, correlating with the inability of CD22 to downregulate the BCR-induced calcium response in these cells. Surprisingly, CD22 remains capable of regulating the ERK2 and JNK pathways in lyn-/- B cells, which may relate to the small residual increase in BCR-induced CD22 phosphorylation. CONCLUSIONS: BCR signal initiation and negative regulation by Fc gamma RIIb1 is not critically dependent on Lyn. In contrast, Lyn plays a particularly important role in the tyrosine phosphorylation of CD22 and in the consequent inhibition of BCR-induced calcium influx. The net result of the Lyn deficiency in B cells is hyperresponsiveness to antigen stimulation, which may explain the autoimmunity observed in lyn-/- mice.

Animals↗
PubMed1998

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↗