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Biomedical subjects

M Lau

Publications and source records attributed to M Lau.

At least 19 recordsLinked to original sources
PubMed2000

Systemic coadministration of chloramphenicol with intravenous but not intracerebroventricular morphine markedly increases morphine antinociception and delays development of antinociceptive tolerance in rats.

Chloramphenicol, an in vitro inhibitor of the glucuronidation of morphine to its putative antianalgesic metabolite, morphine-3-glucuronide (M3G), was coadministered with morphine in adult male Sprague-Dawley rats to determine whether it inhibited the in vivo metabolism of morphine to M3G, thereby enhancing morphine antinociception and/or delaying the development of antinociceptive tolerance. Parenteral chloramphenicol was given acutely (3-h studies) or chronically (48-h studies). Morphine was administered by the i.v. or i.c.v. route. Control rats received chloramphenicol and/or vehicle. Antinociception was quantified using the hotplate latency test. Coadministration of chloramphenicol with i.v. but not i.cv. morphine increased the extent and duration of morphine antinociception by approximately 5.5-fold relative to rats that received i.v. morphine alone. Thus, the mechanism through which chloramphenicol enhances i.v. morphine antinociception in the rat does not directly involve supraspinal opioid receptors. Acutely, parenteral coadministration of chloramphenicol and morphine resulted in an approximately 75% increase in the mean area under the serum morphine concentration-time curve but for chronic dosing there was no significant change in this curve, indicating that factors other than morphine concentrations contribute significantly to antinociception. Antinociceptive tolerance to morphine developed more slowly in rats coadministered chloramphenicol, consistent with our proposal that in vivo inhibition of M3G formation would result in increased antinociception and delayed development of tolerance. However, our data also indicate that chloramphenicol inhibited the biliary secretion of M3G. Whether chloramphenicol altered the passage of M3G and morphine across the blood-brain barrier remains to be investigated.

Analgesics, Opioid↗
PubMed1999

Localization and expression of oxytocin receptor and its messenger ribonucleic acid in peri-implantation phase human endometrium during control and clomiphene-treated cycles.

OBJECTIVES: This study was undertaken to determine expression levels of oxytocin receptor and its gene in peri-implantation phase human endometrium during clomiphene-treated cycles compared with control cycles. STUDY DESIGN: Oxytocin receptor and its messenger ribonucleic acid in peri-implantation phase endometrium during control and clomiphene-treated (50 mg days 5 to 9) cycles of 5 healthy fertile women were determined by immunohistochemical methods, Western blot analysis with monoclonal antibody against amino acids 20 through 40 of the extracellular N-terminal human oxytocin receptor, and reverse transcription-polymerase chain reaction with oligonucleotide primers to amplify the 391-base pair fragment of the oxytocin receptor gene. RESULTS: Oxytocin receptor and its messenger ribonucleic acid were expressed in human peri-implantation phase endometrial samples from both control and clomiphene-treated cycles. The receptor was localized predominantly in the epithelial cells and glands, with little or none detected in the stroma. Oxytocin receptor protein was separated out as a single 70-kd band by Western blot analysis; its relative abundance was significantly reduced during clomiphene-treated cycles. The messenger ribonucleic acid was detected in all endometrium during control and clomiphene-treated cycles, with greater expression during control cycles. CONCLUSIONS: The expressions of oxytocin receptor and its gene in luteal phase human endometrium suggest a functional relevance in modulation of biochemical changes for implantation.

Adult↗
PubMed1999

The HLA dictionary 1999: a summary of HLA-A, -B, -C, -DRB1/3/4/5, -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR, and -DQ antigens.

This report presents serologic equivalents of 90 HLA-A, 190 HLA-B, and 145 HLA-DRB1 alleles. The equivalents cover over 70% of the presently identified HLA-A, -B, and -DRB1 alleles. The dictionary is an update of the one published in 1997 and now also includes equivalents for HLA-C, DRB3, DRB4, DRB5, and DQB1 alleles. The data summarize information obtained by the WHO HLA Nomenclature Committee, the International Cell Exchange (UCLA), the National Marrow Donor Program (NMDP), and by individual laboratories. In addition, a listing is provided of alleles that are expressed as antigens with serologic reaction patterns that differ from the well-established HLA specificities and that often lack official WHO nomenclature. The provided equivalents will be useful in guiding searches for unrelated donors in which patients and/or potential donors are typed by either serology or DNA-based methods. These equivalents will also serve typing and matching procedures for organ transplant programs where HLA typings from donors and from recipients on waiting lists represent mixtures of serologic and molecular typings. Some guidelines are provided for the use of appropriate WHO HLA nomenclature for serologic typings and for generic and allele specific typings obtained with molecular methods. The tables with HLA equivalents and the questionnaire for submission of serology on poorly identified alleles will also be available at the WMDA web page: www.bmdw.org/wmda.

Alleles↗
PubMed1999

Sequence of HLA-A*6808.

A novel HLA-A*68 allele was identified by reference strand conformation analysis of a DNA sample studied for the International Cell Exchange program. Direct sequencing of HLA-A locus PCR products confirmed the presence of A*6602 and an A*68 allele which differed from A*68011 by two nucleotides at positions 538 and 539. The presence of this sequence motif in this allele which has been named A*6808 was verified by DNA sequencing of full-length A*6808 clones. No other coding differences between A*68011 and A*6808 were identified. The two nucleotide substitutions found in A*6808 effect an amino acid difference in the encoded protein at residue 156 within the peptide binding site which may evoke alloreactive immune response after HLA-A68 mismatched transplants.

Black People↗
PubMed1999

The HLA dictionary 1999: a summary of HLA-A, -B, -C, -DRB1/3/4/5, -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens.

This report presents serologic equivalents of 90 HLA-A, 190 HLA-B and 145 HLA-DRB1 alleles. The equivalents cover over 70% of the presently identified HLA-A, -B and -DRB1 alleles. The dictionary is an update of the one published in 1997 and now also includes equivalents for HLA-C, DRB3, DRB4, DRB5 and DQB1 alleles. The data summarize information obtained by the WHO HLA Nomenclature Committee, the International Cell Exchange (UCLA), the National Marrow Donor Program (NMDP) and by individual laboratories. In addition, a listing is provided of alleles which are expressed as antigens with serologic reaction patterns that differ from the well-established HLA specificities and that often lack official WHO nomenclature. The provided equivalents will be useful in guiding searches for unrelated donors in which patients and/or potential donors are typed by either serology or DNA-based methods. These equivalents will also serve typing and matching procedures for organ transplant programs where HLA typings from donors and from recipients on waiting lists represent mixtures of serologic and molecular typings. Some guidelines are provided for the use of appropriate WHO HLA nomenclature for serological typings and for generic and allele specific typings obtained with molecular methods. The tables with HLA equivalents and the questionnaire for submission of serology on poorly identified alleles will also be available at the WMDA web page: www:bmdw.org/wmda.

Alleles↗
PubMed1999

Angular cheilitis after tonsillectomy.

The operation of tonsillectomy requires the oral cavity to be held open mechanically in an unconscious patient, and intra-oral instrumentation to occur. Angular cheilitis may arise as a result of this after operation. This can cause morbidity and delay the re-establishment of a normal diet. The aim of this study was to identify what factors increase the likelihood of developing this problem postoperatively. Sixty patients were randomly selected in a prospective manner. Preoperative, intraoperative and postoperative variables were recorded. The frequency of development of postoperative angular cheilitis was recorded. The prevalence of the condition was related to the prerecorded variables. Parametric analysis showed that the chance of developing angular cheilitis was directly related to the use of diathermy haemostasis (P = 0.05). Logistic regression analysis showed that the odds ratio of developing this complication if diathermy was used is 3.5 (95% confidence intervals 0.99, 12.4) and operation difficulty may also be a relevant variable. No other recorded variables were found to be significant.

Adolescent↗
PubMed1999

A pharmacodynamic explanation for the rapid onset/offset of rapacuronium bromide.

BACKGROUND: Nondepolarizing muscle relaxants differ in their time course at the laryngeal adductors and the adductor pollicis, a result of differences in equilibration delays between plasma and effect sites, the sensitivity of each muscle to the relaxant, and the steepness of the concentration-effect relation at each muscle (the Hill factor). To determine whether similar differences exist for rapacuronium, a muscle relaxant with rapid onset and offset, the authors determined its pharmacodynamic characteristics. METHODS: The twitch tensions of the adductor pollicis and the laryngeal adductors (via a tracheal tube cuff positioned at the vocal cords) were measured in 10 volunteers who were anesthetized with propofoL Rapacuronium, 1.5 mg/kg, was given and blood samples were collected. A semiparametric effect compartment pharmacodynamic model was fit to values for rapacuronium plasma concentrations and twitch tension of the adductor pollicis and laryngeal adductors. RESULTS: Equilibration between the rapacuronium plasma concentration and both effect sites was rapid (typical values for the rate constant for equilibration between plasma and the effect site are 0.405 per min for the adductor pollicis and 0.630 per min for the laryngeal adductors) and was more rapid at the laryngeal adductors than at the adductor pollicis (ratio, 1.59+/-0.16; mean +/- SD). The steady state rapacuronium plasma concentration that depressed twitch tension by 50% and the Hill factor were similar for the two muscles. CONCLUSIONS: The rapid onset and offset of rapacuronium can be explained by the rapid equilibration between concentrations in plasma and at the effect site. Unlike the finding for other nondepolarizing muscle relaxants, the laryngeal muscles are not resistant to rapacuronium.

Adult↗
PubMed1999

Influence of renal failure on the pharmacokinetics and neuromuscular effects of a single dose of rapacuronium bromide.

BACKGROUND: Because renal function affects the elimination of muscle relaxants, each new muscle relaxant must be evaluated in patients with renal failure. Accordingly, the neuromuscular effects and pharmacokinetics of rapacuronium were identified in patients with renal failure. METHODS: Rapacuronium (1.5 mg/kg) was administered to 10 healthy volunteers and 10 patients with renal failure who were undergoing non-transplant surgery, were 18-45 yr old, and were anesthetized with propofol. The adductor pollicis muscle twitch tension was monitored. Plasma samples were obtained frequently for a period of 8 h to measure the concentrations of ORG9487 and its metabolite, ORG9488. Pharmacokinetic parameters were determined using mixed-effects modeling. RESULTS: One patient was excluded from analysis because he was taking phenytoin chronically. Twitch depression at 1 min was less in patients than in healthy volunteers (median values: 92% in patients, 99% in volunteers). The times to 90% and peak twitch depression; to 10%, 25%, and 75% twitch recovery; and to 70% and 80% train-of-four ratios were similar in volunteers and patients. Rapacuronium's clearance was 32% less in patients with renal failure; in both groups, clearance decreased 0.909% per year of age compared with the value in a 30 yr old. The steady state distribution volume was 14% less in women than in men and 16% less in patients than in volunteers. For ORG9488, clearance was 85% less in patients than in volunteers. CONCLUSIONS: The neuromuscular effects of a single dose of rapacuronium are affected minimally by renal failure. However, the decreased clearance of rapacuronium and its potent metabolite in renal failure suggests that repeated dosing of rapacuronium may lead to prolonged effects in patients with renal failure.

Adolescent↗
PubMed1999

Do urinary symptoms correlate with urodynamic findings?

PURPOSE: We determined whether urinary symptomatology correlates with video urodynamic findings. MATERIALS AND METHODS: A total of 115 women with complaints of urinary incontinence completed a 27-item questionnaire. Pelvic examination and video urodynamic study were performed. Subjective findings were scored from 0 to 5, with 5 representing the most severe symptomatology. Patients were divided into 5 subgroups based on etiology of incontinence, and analyzed by Student's t test with p < 0.05 considered statistically significant. RESULTS: Among the 115 patients 11% had normal studies, 38% proximal urethral hypermobility with stress urinary incontinence, 33% intrinsic sphincter deficiency, 11% significant pelvic prolapse and stress urinary incontinence, and 10% detrusor instability. Subjective complaints, such as incontinence during physical activity, were prominent in both stress urinary incontinence groups as well as the prolapse group with stress urinary incontinence. Questions about nocturia, frequency, urgency, urge incontinence, number of pads, number of vaginal deliveries and incomplete emptying were not statistically significant for any group. CONCLUSIONS: Subjective complaints were not helpful in differentiating the etiology of incontinence. Few questions were helpful in predicting which patients would have a normal video urodynamic study.

Adult↗
PubMed1998

E-cadherin and its messenger ribonucleic acid in periimplantation phase human endometrium in normal and clomiphene-treated cycles.

OBJECTIVE: The purpose of this investigation was to determine whether treatment with clomiphene citrate, which is estrogenic and antiestrogenic, affects the expression of the cell adhesion molecule E-cadherin in human periimplantation phase endometrium. STUDY DESIGN: Five healthy women were studied for two cycles each, a control and a treated (clomiphene 50 mg daily, days 5 through 9) cycle. A biopsy specimen of endometrial tissue was studied (8 to 10 days post luteinizing hormone surge) for immunohistochemical localization, Western analysis of E-cadherin with use of a highly specific monoclonal antibody to human E-cadherin, and determination of messenger ribonucleic acid for E-cadherin by reverse transcription-polymerase chain reaction by use of oligonucleotide primers specific to E-cadherin and amplifying a 432 bp fragment. RESULTS: Luteal phase plasma progesterone levels were significantly higher in clomiphene cycles. E-cadherin was immunocytochemically present in endometrium of control and treated cycles with no apparent difference in staining intensity. Western blots revealed the presence of E-cadherin. It was relatively more abundant in clomiphene-treated than control cycles but not significantly different. The message for E-cadherin gene is expressed in endometrium of control (n = 5) and clomiphene cycles (n = 4). CONCLUSIONS: E-cadherin and its gene transcripts are expressed in periimplantation phase endometrium and are not significantly affected by clomiphene treatment.

Adult↗
PubMed1998

The pharmacokinetics and steady state pharmacodynamics of mivacurium in children.

BACKGROUND: The authors previously showed that children require larger infusion rates of mivacurium than adults to maintain target twitch depression. Here, they determined whether there are differences between children and adults in mivacurium's pharmacokinetic and pharmacodynamic properties. METHODS: Twenty-seven patients aged 1-58 yr were anesthetized with nitrous oxide and isoflurane. Cholinesterase activity and adductor pollicis twitch tension in response to train-of-four stimuli were measured. Mivacurium was infused, targeting 90% twitch depression. When twitch was stably depressed 85%-95% for 10 min with no change in infusion rate for 15 min, plasma was sampled to determine concentrations of mivacurium's stereoisomers. Clearance of the trans-trans (Cl(trans-trans)) and cis-trans (Cl(cis-trans)) isomers was determined as the mivacurium infusion rate (adjusted for isomer composition) divided by the concentration of that isomer. Using the Hill equation, assuming equipotency of the trans-trans and cis-trans isomers, and ignoring the contribution of the nonpotent cis-cis isomer, the authors estimated the steady state plasma concentration yielding 90% twitch depression, C90. The effect of age on cholinesterase activity, the infusion rate depressing twitch tension by 90% (IR90), C90, Cl(trans-trans), and Cl(cis-trans) was determined using linear regression. RESULTS: Cholinesterase activity, IR90, and C90 did not vary with age. Both Cl(trans-trans) (r2 = 0.19, P = 0.01) and Cl(cis-trans) (r2 = 0.19, P = 0.02) decreased with age. CONCLUSION: Clearance of mivacurium's potent isomers is larger in younger patients, consistent with the larger mivacurium infusion requirement in children than in adults reported previously.

Adolescent↗
PubMed1998

Opioid-induced analgesia in neonatal dogs: pharmacodynamic differences between morphine and fentanyl.

Whether the analgesic effects of opioids change as a neonate matures is not well understood. To address this issue, we determined the pharmacokinetics and pharmacodynamics of analgesic effects of morphine and fentanyl in 35 dogs aged 1 to 34 days. Opioids were infused to produce analgesia, response times to a noxious thermal stimulus were measured and plasma opioid concentrations were determined. An effect compartment pharmacodynamic model was fit to the values for time to response to determine the rate constant for equilibration (Keo) between plasma and effect-site (Ce) concentrations and analgesic effect (increase in time to response to a noxious stimulus) above baseline per microgram/ml of Ce (delta). A time-to-event data analysis (modeled with a Weibull function) was used to account for censored time to response values. For both opioids, values for Keo did not vary with age. Values for delta decreased with age (i.e., decreasing sensitivity with increasing age), and the magnitude of the change during the first month of life was similar for the two opioids. In the context of our previous study concerning ventilatory depressant effects of these opioids (that sensitivity to morphine, but not to fentanyl, decreased markedly during the first month of life), these results in dogs suggest that fentanyl has greater utility than morphine in neonates during spontaneous ventilation.

Analgesia↗
PubMed1997

Polymorphism at codons 114, 116, 145, and 163 muddle the typing of HLA-B*1304.

Genetic exchanges often muddle the typing of HLA class I molecules, this is also the case for HLA-B*1304. Serologic and molecular DNA class I typing report a B15/B55 type for cell 847, whereas DNA sequencing finds B*5501/B*1304. HLA-B*1304 differs by no more than four amino acids from other HLA-B13 molecules, a comparative analysis of the B13 and B15 families was therefore performed to determine why serologic and molecular DNA approaches report a B15 type for B*1304. Comparisons demonstrate that limited differences individuate the B15 and B13 molecules such that the genetic recombination of codons 145 and 163 in the class I heavy chain's alpha 2 alpha helix prompt B*1304 to exhibit a B15X21 pattern of serologic cross-reactivity. Molecular DNA class I typing approaches are also swayed by genetic recombinations to type B*1304 as a B15 molecule: B15-like nucleotide sequences encoding residues 114, 116, and 145, lead B*1304 to exhibit a B15 PCR amplification pattern. Thus, genetic exchanges encoding key amino acids in the class I heavy chain lead molecular and serologic typing approaches to categorize HLA-B*1304 as a member of the B15 family.

Alleles↗
PubMed1997

Cisapride use during human pregnancy: a prospective, controlled multicenter study.

The objective of this prospective multicenter study was to determine whether cisapride is associated with increased risk of malformations, spontaneous abortions, or decreased birthweight when used during pregnancy. Cases were paired for age, smoking, and alcohol consumption with controls exposed to nonteratogens, as well as with disease-paired controls. One hundred and twenty-nine pregnant women were exposed to cisapride during pregnancy, including 88 during the period of fetal organogenesis. There were no differences in maternal history, birthweight, gestational age at delivery, and rates of livebirths, spontaneous or therapeutic abortions, fetal distress, and major or minor malformations among groups. It is concluded that exposure to cisapride during pregnancy is not associated with a major increased risk of malformations or spontaneous abortions or with decreased birthweight.

Abnormalities, Drug-Induced↗
PubMed1997

Improving the design of muscle relaxant studies. Stabilization period and tetanic recruitment.

BACKGROUND: The results from studies of muscle relaxants show wide variations among institutions. The authors hypothesized that some of this variability could be explained by differences in duration of nerve stimulation before drug administration (stabilization period). METHODS: Train-of-four stimulation was applied every 12 s to both ulnar nerves and adductor pollicis twitch tension was measured in anesthetized participants given 30 micrograms/kg vecuronium. In phase 1, the stabilization period was > 30 min for both extremities. In phase 2-4, stabilization period was 20 min for one extremity and 2 min for the other. In addition, in phase 3, a 2-s 50-Hz tetanus initiated the 2-min stimulation period; in phase 4, duration of tetanus was 5 s. Twitch recovery was recorded until stable for more than 15 min. Time to 25% recovery (clinical duration) was calculated based on two indices: predrug and final (recovery) twitch tension. Values for onset and clinical duration were compared by paired parametric and nonparametric tests. RESULTS: In phase 1, predrug and recovery twitch tension were similar in each extremity, and onset and clinical duration did not differ between extremities, permitting paired comparisons in remaining studies. In phase 2, onset was more rapid with 20-min of prestimulation. With 20-min prestimulation, predrug and recovery twitch tension were similar; with 2-min prestimulation, recovery twitch tension exceeded predrug values. When referenced to predrug twitch tension, clinical duration was shorter with 2-min, that with 20-min prestimulation. Initiating stimulation with 2-s or 5-s 50-Hz tetani (phases 3, 4) abolished differences between extremities in onset and recovery. CONCLUSIONS: With only train-of-four stimulation (no tetani), onset and clinical duration vary with duration of prestimulation, suggesting that a brief period of predrug stimulation is inadequate. However, lengthy prestimulation may be impractical in clinical studies. Tetanic stimulation for 2 or 5 s obviates the need for prolonged stabilization during studies of muscle relaxants.

Adult↗
PubMed1997

Pharmacodynamic modeling of vecuronium-induced twitch depression. Rapid plasma-effect site equilibration explains faster onset at resistant laryngeal muscles than at the adductor pollicis.

BACKGROUND: After bolus doses of nondepolarizing muscle relaxants, the adductor pollicis recovers from paralysis more slowly than the diaphragm and the laryngeal adductors, suggesting that the adductor pollicis is more sensitive than the respiratory muscles to effects of those drugs. In contrast, during onset, the respiratory muscles are paralyzed more rapidly than the adductor pollicis, suggesting that the respiratory muscles are more sensitive than the adductor pollicis. To reconcile these apparently conflicting findings, we determined vecuronium's pharmacokinetics and its pharmacodynamics at both the adductor pollicis and the laryngeal adductors. METHODS: Six volunteers were studied on two occasions during anesthesia with propofol. Mechanical responses to train-of-four stimulation were measured at the adductor pollicis and at the laryngeal adductors. Vecuronium (15-60 micrograms/kg) was given and arterial plasma samples were obtained from 0.5-60 min. Vecuronium doses differed by twofold on the two occasions. A pharmacokinetic model accounting for the presence and potency of vecuronium's 3-desacetyl metabolite and a sigmoid e-max pharmacodynamic model were fit to the resulting plasma concentration and effect (adductor pollicis and laryngeal adductors) data to determine relative sensitivities and rates of equilibration between plasma and effect site concentrations. RESULTS: The steady-state plasma concentration depressing laryngeal adductor twitch tension by 50% was approximately 1.5 times larger than that for the adductor pollicis. The equilibration rate constant between plasma and laryngeal adductor concentrations was about 1.5 faster than that between plasma and adductor pollicis concentrations. The Hill factor (gamma) that describes the steepness of the laryngeal adductor concentration-effect relation was approximately 0.6 times that of the adductor pollicis. CONCLUSIONS: More rapid equilibration between plasma and laryngeal adductor vecuronium concentrations explains why onset is more rapid at the laryngeal adductors than at the adductor pollicis. During recovery, both rapid equilibration and lesser sensitivity of the laryngeal adductors contribute to earlier recovery.

Adult↗
PubMed1997

Bioavailability of intramuscular rocuronium in infants and children.

BACKGROUND: Intramuscular rocuronium, in doses of 1,000 microg/kg in infants and 1,800 microg/kg in children, produces complete twitch depression in 5-6 min. To determine the rate and extent of absorption of rocuronium after intramuscular administration, blood was sampled at various intervals after rocuronium administration by both intramuscular and intravenous routes to determine plasma concentrations (Cp) of rocuronium. METHODS: Twenty-nine pediatric patients ages 3 months to 5 yr were anesthetized with N2O and halothane. The trachea was intubated, ventilation was controlled, and adductor pollicis twitch tension was measured. When anesthetic conditions were stable, rocuronium (1,000 microg/kg for infants and 1,800 microg/kg for children) was injected either intramuscularly (in the deltoid muscle) or intravenously. Four venous plasma samples were obtained from each child 2-240 min after rocuronium administration. A mixed-effects population pharmacokinetic analysis was applied to these values to determine bioavailability, absorption rate constant, and time to peak Cp with intramuscular administration. RESULTS: With intramuscular administration, rocuronium's bioavailability averaged 82.6% and its absorption rate constant was 0.105 min(-1). Simulation indicated that Cp peaked 13 min after rocuronium was given intramuscularly, and that 30 min after intramuscular administration, less than 4% of the administered dose remained to be absorbed from the intramuscular depot. CONCLUSIONS: After rocuronium is administered into the deltoid muscle, plasma concentrations peak at 13 min, and approximately 80% of the administered drug is absorbed systemically.

Androstanols↗