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Biomedical subjects

V W Chan

Publications and source records attributed to V W Chan.

51 records · Page 3Linked to original sources
PubMed1992

Membrane Ig cross-linking regulates phosphatidylinositol 3-kinase in B lymphocytes.

Cross-linking of the B cell AgR results in activation of mature B cells and tolerization of immature B cells. The initial signaling events stimulated by membrane immunoglobulin (mIg) cross-linking are tyrosine phosphorylation of a number of proteins. Among the targets of mIg-induced tyrosine phosphorylation are the tyrosine kinases encoded by the lyn, blk, fyn, and syk genes, the mIg-associated proteins MB-1 and Ig-beta, phospholipase C-gamma 1 and -gamma 2, as well as many unidentified proteins. In this report we show that mIg cross-linking also regulates phosphatidylinositol 3-kinase (PtdIns 3-kinase), an enzyme that phosphorylates inositol phospholipids and plays a key role in mediating the effects of tyrosine kinases on growth control in fibroblasts. Cross-linking mIg on B lymphocytes greatly increased the amount of PtdIns 3-kinase activity which could be immunoprecipitated with anti-phosphotyrosine (anti-tyr(P) antibodies. This response was observed after mIg cross-linking in mIgM- and mIgG-bearing B cell lines and after cross-linking either mIgM or mIgD in murine splenic B cells. Thus, regulation of PtdIns 3-kinase is a common feature of signaling by several different isotypes of mIg. This response was rapid and peaked 2 to 3 min after the addition of anti-Ig antibodies. The anti-Ig-stimulated increase in PtdIns 3-kinase activity associated with anti-Tyr(P) immunoprecipitates could reflect increased tyrosine phosphorylation of PtdIns 3-kinase, increased activity of the enzyme, or both. In favor of the first possibility, the tyrosine kinase inhibitor herbimycin A blocked the increase in ant-Tyr(P)-immunoprecipitated PtdIns 3-kinase activity as well as the anti-Ig-induced tyrosine phosphorylation. Moreover, this response was not secondary to phospholipase C activation but rather seemed to be a direct consequence of mIg-induced tyrosine phosphorylation. Activation of the phosphoinositide pathway by a transfected M1 muscarinic acetylcholine receptor expressed in WEHI-231 B lymphoma cells did not increase the amount of PtdIns 3-kinase activity which could be precipitated with anti-Tyr(P) antibodies. Similarly, inhibition of the phosphoinositide pathway did not abrogate the ability of mIg cross-linking to stimulate this response. Thus, mIg-induced tyrosine phosphorylation regulates PtdIns 3-kinase, an important mediator of growth control in fibroblasts and potentially an important regulatory component in B cells as well.

Animals↗
PubMed1991

Analgesic and pulmonary effects of continuous intercostal nerve block following thoracotomy.

This study examined the beneficial effects and potential systemic toxicity from continuous intercostal nerve block by repeated bolus injections of bupivacaine. In this double-blind, randomized study, 20 post-thoracotomy patients were assigned to receive four doses of either: 20 ml 0.5% bupivacaine with epinephrine 5 micrograms.ml-1 (bupivacaine group, n = 10), or 20 ml preservative-free saline (placebo group, n = 10) through two indwelling intercostal catheters every six hours. Patients receiving intercostal bupivacaine injections had greater decreases in visual analogue pain scores (VAS) (P less than 0.05) and lower 24 hr morphine requirements, 16.6 +/- 4.6 mg vs 35.8 +/- 7.2 mg, than patients in the placebo group (P less than 0.05). Higher post-injection values of forced expiratory volume in one second, forced vital capacity and peaked expiratory flow rate were also observed in the bupivacaine group (P less than 0.01). Repeated intercostal bupivacaine administration did lead to systemic accumulation, but the peak bupivacaine level after 400 mg was low at 1.2 +/- 0.2 microgram.ml-1. Thus, the technique of continuous intercostal nerve block described in this study is an effective treatment for the control of post-thoracotomy pain.

Adult↗
PubMed1991

Interpleural analgesia after thoracotomy.

We examined the effects of the following variables on interpleural analgesia after thoracotomy: addition of epinephrine to local anesthetic, thoracostomy drainage, two-catheter placement, and location of catheter tips. Twenty patients were randomized to have one catheter (paravertebral tip location) or two catheters (paravertebral and lateral thoracic wall tip locations). Interpleural catheters were sutured to the parietal pleura by the surgeon at time of wound closure. Patients were then randomly assigned to receive 20 mL of 0.5% bupivacaine with 1:200,000 epinephrine through the single catheter or 10 mL of 0.5% bupivacaine with or without 1:200,000 epinephrine through each of the two catheters while supine. Bupivacaine concentrations in whole blood and in thoracostomy drainage fluid were assayed by gas chromatography. Actual content of bupivacaine in the drainage fluid was calculated. Degree of analgesia was assessed by verbal numerical pain scores over the first 4 h and opioid demand thereafter. Addition of epinephrine to bupivacaine did not influence the degree of analgesia. Approximately 30%-40% of any administered dose of bupivacaine was lost via the thoracostomy tube over a 4-h period. There was no correlation between the true initial dose (100 mg minus thoracostomy drainage) and Cmax. Use of two catheters resulted in significantly less opioid requirements after an initial 8-h period. Failure to achieve adequate interpleural analgesia in postthoracotomy patients may be related to loss of anesthetic via thoracostomy drainage, presence of extravasated blood and tissue fluid in the pleural space, and possibly sequestration and channeling of flow of local anesthetic by restricted motion of an operated lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Bupivacaine↗
PubMed1990

Evidence that chemical modification of a positively charged residue at position 189 causes the loss of catalytic activity of iron-containing and manganese-containing superoxide dismutases.

The Escherichia coli, Bacillus stearothermophilus, and human manganese-containing superoxide dismutases (MnSODs) and the E. coli iron-containing superoxide dismutase (FeSOD) are extensively inactivated by treatment with phenylglyoxal, an arginine-specific reagent. Arg-189, the only conserved arginine in the primary sequences of these four enzymes, is also conserved in the three additional FeSODs and five of the six additional MnSODs sequenced to date. The only exception is Saccharomyces cerevisiae MnSOD, in which it is conservatively replaced by lysine. Treatment of S. cerevisiae MnSOD with phenylglyoxal under the same conditions used for the other SODs gives very little inactivation. However, treatment with low levels of 2,4,6-trinitrobenzenesulfonate (TNBS) or acetic anhydride, two lysine-selective reagents that cause a maximum of 60-80% inactivation of the other four SODs, gives complete inactivation of the yeast enzyme. Total inactivation of yeast MnSOD with TNBS correlates with the modification of approximately five lysines per subunit, whereas six to seven acetyl groups per subunit are incorporated on complete inactivation with [14C]-acetic anhydride. It appears that the positive charge contributed by residue 189, lysine in yeast MnSOD and arginine in all other SODs, is critical for the catalytic function of MnSODs and FeSODs.

Amino Acid Sequence↗
PubMed1989

Inactivation of human thrombin by water-soluble carbodiimides. The essential carboxyl has a pKa of 5.6 and is one other than Asp-189.

Human thrombin is inactivated by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) or 1-ethyl-3-(4-azonia-4,4-dimethylpentyl)carbodiimide (EAC) by a second order process. A plot of the pseudo-first order rate constant for inactivation by 20 mM EDC at different pH values from 4.2 to 7.7 at 25 degrees C shows that this inactivation is due to the modification of a protonated carboxyl with a pKa of 5.6. The rate of inactivation by EDC at pH 6.0 is reduced, but not eliminated by saturating levels of the competitive inhibitor dansyl-L-arginine N-(3-ethyl-1,5-pentanediyl)amide, suggesting that the essential carboxyl modified is one other than Asp-189 in the substrate specificity pocket of thrombin. Complete inactivation by 14C-EAC correlates with the incorporation of approximately 2.5-3 EACs per thrombin.

Aspartic Acid↗
PubMed1989

Retention modification of nucleic acid constituents in reversed-phase high-performance liquid chromatography.

Secondary equilibria in reversed-phase liquid chromatography have been investigated as a means of enhancing selectivity and optimizing separations of nucleic acid constituents. The retention behavior of various nucleotides, nucleosides and modified compounds has been examined as a function of five different metal ion additives in the mobile phase: K+, Mg2+, Mn2+, Ni2+ and Zn2+. Complexation of the solute molecules with the metal ions changes the electronic structure and alters solute-solvent interactions. Alkali and alkaline earth metals bind primarily to phosphate groups while transition metals also interact with the N7 of purine bases. All nucleotides were found to be eluted very close to the void volume of the high-performance liquid chromatographic column without any metal additive, but retention increased as the concentration of a given cation increased. The transition metals were found to have the greatest effect, with affinities for nucleotide monophosphates on the order of 100 times greater than potassium, and 10 times that of magnesium. Differences in affinity based upon phosphate structure (i.e., cyclic vs. linear), phosphate position (e.g., 2'- vs. 3'-monophosphates), and base modification were also noted. The retention of most nucleosides, unlike the charged compounds, remained relatively constant as the ionic strength or type of cation was varied. Also, improvements were obtained in the resolution of some oligonucleotides with the addition of divalent ions to a potassium buffer mobile phase.

Cations↗
PubMed1988

Inactivation of bovine thrombin by water-soluble carbodiimides: the essential carboxyl group has a pKa of 5.51.

Bovine thrombin is rapidly and completely (greater than 99%) inactivated by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) in a pseudo-first-order process. A plot of the pseudo-first-order rate constant for inactivation by 20 mM EDC at different pH values from pH 4.0 to 7.7 at 25 degrees C shows that inactivation is critically dependent on the protonated form of an acidic side chain with a pKa of 5.51. Significant protection against inactivation is provided by the competitive inhibitor dansyl-L-arginine N-(3-ethyl-1,5-pentanediyl)amide, suggesting that the essential carboxyl group may be involved in substrate binding. 1-Ethyl-3-(4-azonia-4,4-dimethylpentyl)carbodiimide (EAC) inactivates thrombin much more rapidly than EDC under the same conditions.

Animals↗
PubMed1988

Anaesthesia for transsphenoidal surgery in a patient with extreme gigantism.

The management of anaesthesia for transsphenoidal removal of a pituitary adenoma in a true pituitary giant with acromegaly is described. Problems which may be anticipated in such a patient and an approach to their management are discussed, with particular emphasis upon the need for thorough preoperative assessment of the upper airway and the provision of adequate pulmonary ventilation during anaesthesia.

Acromegaly↗
PubMedDate not supplied

What is the relationship between paresthesia and nerve stimulation for axillary brachial plexus block?

BACKGROUND AND OBJECTIVES: To quantify the motor threshold current of a needle following elicitation of paresthesia during axillary brachial plexus block (ABPB). METHODS: This is a prospective, observational study of ABPB in 72 patients. Having elicited paresthesia, the minimum current required to produce a motor response was noted. The development and success of the block were subsequently followed. RESULTS: Nineteen blocks were excluded (18 because of arterial puncture and 1 blocked needle). Of the remaining 53 blocks, 41 (77%) produced a motor response at 0.5 mA or less. The median current was 0.17 mA (range, 0.03 to 3.3 mA). The site of initial paresthesia and subsequent motor response were related in 43 (81%) of cases. CONCLUSIONS: A needle position causing paresthesia produced a motor response at 0.5 mA or less in 77% of cases studied. This current may, therefore, be a reasonable threshold to aim for when performing an ABPB.

Anesthetics, Local↗
PubMedDate not supplied

Analgesic effects of low-dose ropivacaine for interscalene brachial plexus block for outpatient shoulder surgery-a dose-finding study.

BACKGROUND AND OBJECTIVES: Interscalene brachial plexus block (ISB) with low-dose bupivacaine provides effective postoperative shoulder analgesia in outpatients. The analgesic effect of low-dose ropivacaine for ISB is unknown. METHODS: In this double-blind study, 66 outpatients scheduled to undergo arthroscopic shoulder surgery were randomly assigned to receive an ISB with 10 mL of 0.125%, 0.25%, or 0.5% ropivacaine before surgery. Postoperative verbal pain rating score, analgesic consumption, and the extent of motor and sensory block was assessed for 120 minutes after surgery. RESULTS: The degree of shoulder analgesia was dose dependent. Postoperative pain scores were lowest with 0.5% ropivacaine, and analgesic was not required in the hospital in 70% of the patients who received 0.25% and 0.5% ropivacaine, compared to 30% with 0.125% ropivacaine (P < .03). In the patients who required no analgesic in the hospital, the time to first oral analgesic at home was approximately 10 hours irrespective of ropivacaine concentration. Motor and sensory block distal to the elbow was detected in 25% of the patients in the 0.5% group but none in the 0.125% group. CONCLUSIONS: Interscalene brachial plexus block with low-dose ropivacaine, 10 mL of 0.25% and 0.5%, provides effective long-lasting shoulder analgesia in a majority of patients after arthroscopic surgery.

Adult↗
PubMedDate not supplied

A comparative study of low-dose hyperbaric spinal lidocaine 0.5% versus 5% for continuous spinal anesthesia.

BACKGROUND AND OBJECTIVES: Concerns of cauda equina syndrome have discouraged clinicians to use 5% lidocaine for continuous spinal anesthesia. Earlier reports indicated that single-shot spinal lidocaine 0.5% is effective for minor gynecologic and perianal surgery. In the present study, we evaluate the anesthetic and hemodynamic effects of low dose hyperbaric 0.5% lidocaine for continuous spinal anesthesia and compare with those of the 5% lidocaine solution in patients undergoing urologic surgery. METHODS: Spinal anesthesia was induced via an indwelling subarachnoid catheter in 42 elderly male patients (range, 57-84 years) undergoing transurethral prostate and bladder procedures. Patients were randomly assigned to receive an initial 30-mg bolus of hyperbaric lidocaine in the form of either 6 mL of 0.5% solution or 0.6 mL of 5% solution. Additional 30-mg boluses (to a total of 90 mg) were given, if necessary, to establish initial sensory block to T10 or higher and lower limb paralysis. Supplemental doses of 30 mg or less were given during surgery, as needed. Dermatomal level of sensory anesthesia and degree of motor blockade were assessed at regular intervals by a blinded observer. Heart rate and blood pressure (mean systolic and diastolic) values were monitored at regular intervals. RESULTS: Forty patients were studied successfully. Both hyperbaric 0.5% and 5% lidocaine provided adequate surgical anesthesia in 75% (30/40) of patients after a single 30-mg dose. A median peak sensory level of T5 (range, T2-T9) achieved within 11.1 +/- 4.5 minutes in patients receiving the 0.5% solution was significantly higher than the peak sensory level of T7 (range, T4-T12) in the 5% group (P = .043). The duration of surgical anesthesia after a 30-mg dose was similar in both groups--48.1 +/- 12.1 minutes versus 50.8 +/- 16.5 minutes respectively. Of the 30 patients (15 in each group) who received 30 mg initially, 25 required repeat lidocaine dosing through the catheter during surgery. The maximum decrease in heart rate and blood pressure values was within 10% and 20%, respectively, of baseline values in both groups. In the remaining patients (10/40), anesthesia was achieved successfully in five patients in the 0.5% group and three patients in the 5% group after two 30-mg lidocaine boluses (60 mg) and two patients in the 5% group after three 30-mg boluses (90 mg). CONCLUSIONS: Continuous spinal anesthesia produced by 0.5% lidocaine with 7.5% dextrose is as effective as that produced by the 5% lidocaine solution in elderly patients undergoing urologic surgery. An initial 30-mg bolus delivered via indwelling subarachnoid catheter was sufficient to achieve surgical anesthesia for approximately 50 minutes in most patients. Hemodynamic effects of the two lidocaine solutions were also comparable.

Aged↗
PubMedDate not supplied

Temperature changes and shivering after epidural anesthesia for cesarean section.

Changes in bladder, tympanic membrane, and skin temperature were monitored in two groups of parturients after they received epidural anesthesia for elective Cesarean sections. Group 2 patients (n = 21) received warm intravenous crystalloid and prep solutions as well as extra body covering, whereas Group 1 patients (n = 19) did not. The drop in bladder temperature over the course of the procedure was significantly greater in Group 1 patients (1.0 +/- .02 degrees C vs. 0.6 +/- 0.01 degrees C, SEM p less than 0.05). The incidence of shivering was similar in both groups (52% vs. 68%, x2 = 0.42). The peak onset of shivering occurred within 10 minutes of epidural anesthesia and preceded any significant decline in core temperature. However, a positive correlation was noted between shivering and bladder temperature decline over the full course of Cesarean section.

Adult↗
PubMedDate not supplied

Impact of patient-controlled analgesia on required nursing time and duration of postoperative recovery.

BACKGROUND AND OBJECTIVES: Patient-controlled analgesia (PCA) offers effective postoperative pain management. However, the evidence of economic benefits associated with its use is lacking. Although suggestive, the potential economic advantages of PCA in saving nursing time and shortening hospital stay need objective documentation. METHODS: This study compared the effects of morphine administered by PCA systems with intramuscular (i.m.) morphine injection on patient analgesic response, satisfaction, nursing time requirements, and postoperative recovery in 23 patients undergoing "open" cholecystectomy and 44 patients undergoing lumbar laminectomy and bony fusion. After the operation, patients in the PCA group received 1.5-2 mg morphine with a lockout of 5-10 minutes on demand, whereas those in the i.m. group received 0.15-0.2 mg/kg every 4 hours on demand. Visual analog scale (VAS) pain scores and satisfaction scores were evaluated at 4-hour intervals while nursing time spent on both analgesia-related and non-analgesia-related activities was recorded continuously by a team of independent observers on the ward. Recovery time profile for the return of bowel function, activities of daily living, ambulation without support, and length of hospital stay was also recorded. RESULTS: It was found that morphine consumption, VAS, and satisfaction scores were similar in both PCA and i.m. treatment groups following both types of surgery. However, the delay in nurse response to i.m. morphine request ranged from 27.2 +/- to 42.1 +/- 11.8 minutes. The demand of nursing time on analgesia administration was less with PCA. The magnitude of time saving was 10 min/patient/d in cholecystectomy patients and 13 min/patient/d in laminectomy patients. The speed of postoperative patient recovery was similar between the two analgesia groups. Length of hospital stay following cholecystectomy was shorter--92.0 +/- 5.9 hours with PCA versus 128.6 +/- 22.2 hours with i.m. (not statistically significant)--whereas that following laminectomy was not different. CONCLUSIONS: Data in this study have demonstrated some beneficial effects of PCA on nursing time requirements when it was used following cholecystectomy and lumbar laminectomy at the University of Toronto: however, the magnitude of these benefits was less than previously reported. The effects of PCA on postoperative recovery and hospital stay, however, were not significantly different from i.m. therapy.

Adult↗
PubMedDate not supplied

Analgesic effect of interscalene block using low-dose bupivacaine for outpatient arthroscopic shoulder surgery.

BACKGROUND AND OBJECTIVES: Although interscalene brachial plexus block (ISBPB) is often used to provide anesthesia for arthroscopic shoulder surgery, its selective analgesic effect, provided by low-dose local anesthetic, has not been studied. We hypothesized that ISBPB using a low volume and low concentration of bupivacaine can provide effective postoperative analgesia for shoulder surgery without producing significant sensory or motor block elsewhere. METHODS: In this double-blind study, 30 outpatients scheduled to undergo shoulder arthroscopy were randomly assigned to receive either an ISBPB with 10 mL 0.125% bupivacaine with epinephrine 1:400,000 (n = 15) or 10 mL of normal saline (n = 15). The block was performed preoperative, prior to a standardized general anesthetic. Postoperative pain scores, imorphine and oral analgesic consumption, recovery profile, and patient satisfaction were recorded. RESULTS: In the ISBPB group, verbal analog pain scores within 120 minutes after surgery were lower, morphine consumption in the postanesthesia care unit was significantly lower (2.7+/-2.6 mg vs 9.5+/-5.2 mg), the time to postoperative administration of the first systemic or oral analgesic was significantly longer (141+/-182 minutes vs 13+/-10 minutes), the degree of motor and sensory block 120 minutes after surgery was minimal, time to reach hospital discharge criteria was earlier, and patient satisfaction with postoperative analgesia at 24-hour follow-up was greater. Thirty-three percent of the patients receiving ISBPB did not require any analgesic prior to hospital discharge. CONCLUSIONS: Interscalene brachial plexus block with low-dose bupivacaine is a useful and selective analgesic technique for outpatient shoulder arthroscopic surgery.

Adult↗