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Biomedical subjects

M Lau

Publications and source records attributed to M Lau.

At least 55 records · Page 3Linked to original sources

The search for HLA-matched donors: a summary of HLA-A*, -B*, -DRB1/3/4/5* alleles and their association with serologically defined HLA-A, -B, -DR antigens.

This report summarizes data obtained from several large studies including the WHO HLA Nomenclature Committee, the International Cell Exchange, UCLA, the British Society for Histocompatibility and Immunogenetics Rare Cell Exchange and the National Marrow Donor Program and individual laboratories aimed at identifying a serologic type for specific HLA-A,-B,-DRB allelic products. Alleles that are poorly characterized at the serologic level are indicated and an approach is suggested for obtaining the information needed to clarify their serologic typing. The tables provided will be useful in guiding searches for an unrelated donor in which patient and/or potential donors are typed either by serology or by DNA-based methods and will provide a "dictionary" of potential equivalents between HLA "types" obtained by the two methods.

Alleles↗

Predicting poor neonatal outcome: a comparative study of noninvasive antenatal testing methods.

OBJECTIVE: The assessment of fetal well-being in the third trimester of pregnancy depends on many variables including fetal size, amniotic fluid volume, umbilical cord arterial Doppler waveforms, the nonstress test, and the biophysical profile, yet little has been written that directly compares these variables. In this study, we compared amniotic fluid indexes, umbilical cord arterial Doppler waveforms, nonstress tests, and biophysical profiles for predicting poor neonatal outcomes in fetuses who are small for gestational age (SGA). SUBJECTS AND METHODS: From April 11, 1994, through August 1, 1995, a cohort of 108 SGA fetuses was identified. Follow-up was available in 97 of these cases. Receiver operating characteristic curves were constructed for Doppler systolic:diastolic ratios and for amniotic fluid indexes. Student's t test and logistic regression analysis were used to compare umbilical cord arterial Doppler imaging, amniotic fluid indexes, the nonstress test, and the biophysical profile for predicting poor neonatal outcome. RESULTS: Of the 30 fetuses who had poor outcomes, five were emergency cesarean deliveries, three died, three had intracranial hemorrhages, one had a cerebral infarct, 12 had prolonged admission to the neonatal intensive care unit (NICU) (> 10 days), and six had NICU admissions at term. Of the variables we assessed, the sensitivities for predicting poor outcome were as follows: cord Doppler imaging, 64%; low amniotic fluid volume (oligohydramnios), 32%; biophysical profile, 18%; and nonstress test, 14%. Receiver operating characteristic curves showed that a systolic:diastolic ratio of 4.0 and an amniotic fluid index of 5 cm (independent of gestational age) were the most accurate cutoff values for predicting poor outcome. Logistic regression analysis showed that amniotic fluid indexes and umbilical cord arterial Doppler imaging were independent predictors of poor outcome and that the predictive value of the biophysical profile varied according to the amniotic fluid index. CONCLUSION: Doppler waveform abnormalities were the most accurate predictor of poor neonatal outcome in a cohort of SGA fetuses. Umbilical cord arterial Doppler waveform analysis should be included in the surveillance of SGA fetuses.

Amniotic Fluid↗

Ovarian abscess 15 months after vaginal hysterectomy. A case report.

BACKGROUND: Ovarian abscess is a primary infection of ovarian parenchyma. Since 1869, only 44 cases after vaginal hysterectomy have been reported in the medical literature. The pathophysiology of bacterial infection in these cases is different from the traditional ascending mechanism. CASE: A 28-year-old woman presented with complaints of lower abdominal pain and fever 15 months after transvaginal hysterectomy. Her white blood cell count was 22,700/mm3, with 90% neutrophils. Bimanual examination revealed a tender mass in the cul-de-sac, and computed tomography showed a large, multiloculated pelvic mass. Laparotomy, pathologic examination and microbiologic study confirmed the diagnosis of ovarian abscess. CONCLUSION: Our case represents another rare posthysterectomy ovarian abscess. Most of these cases were managed by surgery and antibiotic treatment.

Abscess↗

Does age or pseudocholinesterase activity predict mivacurium infusion rate in children?

Previous studies have suggested that the mivacurium infusion rate to maintain target twitch depression is greater in children than in adults, and that there is only a limited relationship between pseudocholinesterase activity and mivacurium infusion rate in children. We therefore examined whether mivacurium infusion rates are larger in children than in adults, and whether pseudocholinesterase activity influences mivacurium infusion rate in children. In 20 children aged 1-9 yr, mechanical twitch response to ulnar nerve train-of-four stimulation was measured; concurrent data were obtained in 14 adults aged 18-58 yr. All patients were anesthetized with N2O and isoflurane, 0.75 minimum alveolar anesthetic concentration (MAC) (age-adjusted). Mivacurium was infused at constant rates for > 15 min targeting 50% and 90% twitch depression. The Hill equation was fit to the resulting values for twitch depression versus mivacurium infusion rate to predict infusion rates producing 50% and 90% twitch depression (IR50 and IR90, respectively). The relationship of IR50 and IR90 to pseudocholinesterase activity was determined by linear regression; values for children and adults were compared by analysis of covariance. For children, IR50 (r2 = 0.22, P = 0.038) but not IR90 (r2 = 0.11 P = 0.21) was related to pseudocholinesterase activity. Infusion rates were approximately twice as large in children as in adults. We confirm that mivacurium infusion rates are larger in children than in adults and demonstrate a relationship between pseudocholinesterase activity and infusion rates.

Adult↗

Intramuscular rocuronium in infants and children. Dose-ranging and tracheal intubating conditions.

BACKGROUND: Rocuronium's rapid onset and intermediate duration of action with intravenous administration suggests that intramuscular administration might facilitate tracheal intubation without producing prolonged paralysis. Accordingly, in infants and children, the authors measured onset at the adductor pollicis and respiratory muscles to determine the optimal dose (phase I), then gave this optimal dose to determine the optimal time for tracheal intubation (phase II). METHODS: The authors studied 45 unpremedicated patients aged 3 months to 5 yr. In phase I, 25 patients were anesthetized with nitrous oxide and halothane and breathed spontaneously; twitch tension and minute ventilation were measured. Rocuronium (800-2,400 micrograms/kg) was injected into the quadriceps or deltoid muscle; doses varied, using an "up-down" technique, the goal being to bracket the dose depressing twitch 75-90% within 5 min. In phase II, deltoid injections of the optimal dose from phase I (infants: 1,000 micrograms/kg; children: 1,800 micrograms/kg) were given to 20 patients anesthetized with 0.82-1.0% halothane. Tracheal intubation was attempted 1.5-3.0 min later; time to tracheal intubation was varied, using an "up-down" technique. RESULTS: In phase I, 5 of 7 patients given quadriceps injections (1,200-2,200 micrograms/kg) had slow onset of twitch and ventilatory depression. With deltoid injections (800-2,400 micrograms/kg), all patients developed complete twitch depression; median time to 50% depression of minute ventilation was 3.2 min in infants and 2.8 min in children. In phase II, intubating conditions were consistently adequate or good-excellent at 2.5 min in infants and 3.0 min in children. Initial twitch recovery was at 57 +/- 13 min (mean +/- SD) in infants and 70 +/- 23 min in children. CONCLUSIONS: Deltoid injections of rocuronium, 1,000 micrograms/kg in infants and 1,800 micrograms/kg in children, rapidly permit tracheal intubation in infants and children, despite a light plane of anesthesia. Duration of action of these large doses might limit clinical utility.

Androstanols↗

Novel alleles HLA-B*7802 and B*51022: evidence for convergency in the HLA-B5 family.

We have characterized two novel HLA-B alleles, B*7802 and B*51022. The Caucasian-derived variant B*7802 most resembles the African-derived variant B*7801, from which B*7802 differs by two nucleotides. Only one of these modifications, however, is translated: a tyrosine for aspartate substitution occurs at residue 74 in B*7802, while the second nucleotide difference reflects a proximal synonymous substitution in codon 23. A second variant, B*51022, differs synonymously only at codon 23 from B*51021. Comparative analysis of the B5 CREG demonstrates that other pairs of B5 alleles differ synonymously only at codon 23 or synonymously at codon 23 and non-synonymously at a second more distal location. Contrary to the genesis of like pairs of B5 alleles via introduction of coordinate yet distant mutagenic events onto a single B5 progenitor, we postulate that synonymously different B5 progenitor molecules, B5ATT and B5ATC, are evolving in convergence to generate homologous B5 allele pairs differing silently at codon 23. Our finding that B*7802 is a single amino acid away from complete convergence with B*7801 and that B*51022 and B*51021 are in complete convergence is exemplary of such evolution.

Alleles↗

Blood flow characteristics of ovarian tumors: implications for ovarian cancer screening.

OBJECTIVES: Our purpose was to investigate the blood flow characteristics of benign and malignant ovarian tumors. Questions posed by our research were as follows: (1) Can malignant ovarian tumors be predicted by color flow Doppler imaging? (2) What are the sensitivity, specificity, and positive and negative predictive values of such prediction? (3) Which color flow Doppler parameter is superior in its accuracy of prediction? STUDY DESIGN: One hundred twenty-three consecutive patients seen for suspected pelvic masses were evaluated by transvaginal ultrasonography and color flow Doppler imaging. A morphologic assessment was initially performed, followed by color flow Doppler analysis. A comparison of findings between the benign and malignant tumors was made by analyzing different thresholds of the intratumoral pulsatility and resistance index values by means of receiver-operator characteristic curves. By calculation of the area index under each receiver-operator characteristic curve the efficiency of the pulsatility and resistance index values in predicting malignancy was determined. RESULTS: Fifty-six benign and 23 malignant tumors were pathologically confirmed. Patients with malignant tumors were more likely to be postmenopausal and were older than patients with benign tumors. Malignant tumors were more likely to be larger and to have either a complex or solid pattern. Absent color flow was more common in benign tumors, and increased color flow was found equally among benign and malignant tumors. There was no difference in systolic, diastolic, or mean velocities between benign and malignant tumors. The calculated pulsatility and resistance index values were lower in patients with malignant tumors compared with those with benign tumors. No significant difference exists in performance of either the pulsatility or resistance index in predicting malignancy. The best thresholds for predicting malignancy were obtained with a pulsatility index of 1.0 and resistance index of 0.6. CONCLUSIONS: Transvaginal ultrasonography is accurate in distinguishing benign from malignant ovarian tumors. Color flow Doppler findings are not specific enough to be used independent of gray-scale ultrasonography.

Female↗

Nucleotide sequence analysis of HLA-B*1523 and B*8101. Dominant alpha-helical motifs produce complex serologic recognition patterns for the HLA-B"DT" and HLA-B"NM5" antigens.

Assigning a precise serologic specificity to the class I HLA-B"NM5" and HLA-B"DT" molecules has proven difficult, with patterns of serologic cross-reactivity suggesting that NM5 is most like antigens in the B5 CREG and that DT is either B7 or B40 like. To better understand the relationship these antigens share with other HLA-B molecules we determined the nucleotide sequence of the alleles encoding HLA-B"NM5" and HLA-B"DT". Sequencing results show that NM5 shares the most overall sequence homology with the B70 antigens and that differences at the alpha-helical Bw4/Bw6 epitope preclude serologic cross-reactivity between NM5 and the B70 antigens. Accordingly, NM5 has been assigned the name B*1523. The strong serologic impact of helical sequence conservations and variations is reiterated for the class I HLA-B"DT" molecule. Comparative analysis demonstrates that sequence conservations in the first domain's alpha-helix stimulate cross-reactivity between HLA-B"DT" and HLA-B7, whereas epitopes conserved in the second domain's alpha-helix impel cross-reactivity between HLA-B"DT" and HLA-B48. To convey the unique lineage of this hybrid B7/B48 molecule the name HLA-B*8101 has been assigned to HLA-B"DT".

Alleles↗

The effect of plasma cholinesterase activity on mivacurium infusion rates.

Although mivacurium is eliminated by plasma cholinesterase, previous investigations have revealed either no relationship or limited correlation between mivacurium infusion rates (IRs) and plasma cholinesterase activity. Assuming that such a relationship should exist, we used a novel approach to better demonstrate the relationship in humans. Fourteen isoflurane-anesthetized adults underwent standard neuromuscular monitoring. Mivacurium was then infused at 1.0 micrograms.kg-1.min-1 until twitch tension stabilized. The IR was then adjusted, using the Hill equation, to produce approximately steady state 50% (n = 14) or 90% (n = 13) twitch depression. Using these values for IR and steady-state twitch depression, the IRs expected to produce 50% and 90% twitch depression (IR50 and IR90, respectively) were estimated by on nonlinear regression. Both IR50 (r2 = 0.51, P < 0.005) and IR90 (r2 = 0.48, P < 0.01) were related to plasma cholinesterase activity; the coefficient of the Hill equation did not vary with plasma cholinesterase activity. We conclude that mivacurium IRs are, as expected, influenced by the activity of the enzyme responsible for its elimination.

Adolescent↗

Recovery of hepatic drug extraction after hypothermic preservation.

BACKGROUND: To determine whether liver preservation before transplantation impairs hepatic drug metabolism, hepatic extraction of drugs with different metabolic pathways (fentanyl, morphine, and vecuronium) in isolated rat livers was measured either immediately or after 24 h of hypothermia at 4 degrees C using a standard preservation-reperfusion sequence. METHODS: Isolated rat livers were perfused via the portal vein for 30 min to document initial viability. Test livers (n = 5) were perfused with iced Belzer solution, stored for 24 h at 4 degrees C, and flushed with 6% hetastarch. After hypothermic preservation for 24 h, or in control livers (n = 5) immediately after the 30-min perfusion, livers were perfused single-pass at a constant flow rate with solutions containing fentanyl, morphine, and vecuronium at 37 degrees C. Perfusate and bile samples were obtained at regular intervals for 64 min, after which liver tissue was harvested for analysis. Drug concentrations were measured using radioimmunoassay and gas chromatography. Metabolic capacity of the liver was estimated from the extraction fraction of each drug at steady-state. RESULTS: After warming to 37 degrees C, preserved livers consumed oxygen and produced bile at rates similar to that of control livers. Hypothermic preservation did not affect extraction of fentanyl and morphine. Vecuronium extraction was initially less in preserved livers, but this difference disappeared as the preserved livers returned to 37 degrees C (< 16 min). Biliary excretion and tissue concentrations of vecuronium were similar in each group. CONCLUSIONS: Hypothermic preservation does not significantly impair extraction of these drugs in this liver preservation model. If these results apply to human liver transplantation, little danger of drug accumulation exists during the early postoperative period if hepatic function is normal.

Animals↗

The magnitude and time course of vecuronium potentiation by desflurane versus isoflurane.

BACKGROUND: Preliminary studies suggest that desflurane and isoflurane potentiate the action of muscle relaxants equally. However, variability between subjects may confound these comparisons. A crossover study was performed in volunteers on the ability of desflurane and isoflurane to potentiate the neuromuscular effect of vecuronium, to influence its duration of action, and on the magnitude and time course of reversal of potentiation when anesthesia was withdrawn. METHODS: Adductor pollicis twitch tension was monitored in 16 volunteers given 1.25 MAC desflurane on one occasion, and 1.25 MAC isoflurane on another. In eight subjects, vecuronium bolus dose potency was determined using a two-dose dose-response technique; the vecuronium infusion dose requirement to achieve 85% twitch depression also was determined. Also in these subjects, the magnitude and time course of spontaneous neuromuscular recovery were determined when the anesthetic was withdrawn while maintaining a constant vecuronium infusion. In the other eight subjects, the time course of action of 100 micrograms/kg vecuronium was determined. RESULTS: Vecuronium's ED50 and infusion requirement to maintain 85% twitch depression were 20% less during desflurane, compared to isoflurane, anesthesia; vecuronium plasma clearance was similar during the two anesthetics. After 100 micrograms/kg vecuronium, onset was faster and recovery was longer during desflurane anesthesia. When the end-tidal anesthetic concentration was abruptly reduced from 1.25 to 0.75 MAC, twitch tension increased similarly (approximately 15% of control), and time for the twitch tension to reach 90% of the final change was similar (approximately 30 min) with both anesthetics. Decreasing anesthetic concentration from 0.75 to 0.25 MAC increased twitch tension by 46 +/- 10% and 25 +/- 7% of control (mean +/- SD, P < 0.001) with desflurane and isoflurane, respectively; 90% response times for these changes were 31 +/- 10 min and 18 +/- 7 min (P < 0.05), respectively. CONCLUSIONS: Desflurane potentiates the effect of vecuronium approximately 20% more than does an equipotent dose of isoflurane.

Adult↗

Edrophonium increases mivacurium concentrations during constant mivacurium infusion, and large doses minimally antagonize paralysis.

BACKGROUND: Mivacurium, a nondepolarizing muscle relaxant, is metabolized by plasma cholinesterase. Although edrophonium does not alter plasma cholinesterase activity, we have observed that doses of edrophonium that antagonize paralysis from other nondepolarizing muscle relaxants are less effective with mivacurium. We speculated that edrophonium might after metabolism of mivacurium, thereby hindering antagonism of paralysis. Accordingly, we determined the effect of edrophonium on neuromuscular function and plasma mivacurium concentrations during constant mivacurium infusion. METHODS: We infused mivacurium to maintain 90% depression of adductor pollicis twitch tension and then gave edrophonium in doses ranging from 125-2,000 micrograms/kg without altering the mivacurium infusion. Peak twitch tension after edrophonium was determined to estimate the dose of edrophonium antagonizing 50% of twitch depression for antagonism of mivacurium; plasma cholinesterase activity and mivacurium concentrations before and after edrophonium were measured. Additional subjects were given 500 micrograms/kg edrophonium to antagonize continuous infusions of d-tubocurarine and vecuronium. RESULTS: With mivacurium, edrophonium increased twitch tension in a dose-dependent manner: the dose of edrophonium antagonizing 50% of twitch depression was 2,810 micrograms/kg. The largest dose of edrophonium (2,000 micrograms/kg) produced only 45 +/- 7% antagonism. Edrophonium, 500 micrograms/kg, antagonized mivacurium markedly less than it antagonized d-tubocurarine and vecuronium. Edrophonium increased plasma concentrations of the two potent stereoisomers of mivacurium 48% and 79%, these peaking at 1-2 min; plasma cholinesterase activity was unchanged. CONCLUSIONS: Edrophonium doses that antagonize d-tubocurarine and vecuronium are less effective in antagonizing the neuromuscular effects of mivacurium during constant infusion. Edrophonium increases plasma mivacurium concentrations, partly or completely explaining its limited efficacy; the mechanism by which edrophonium increases mivacurium concentrations remains unexplained. Our results demonstrate that antagonism of mivacurium by edrophonium is impaired, and therefore we question whether edrophonium should be used to antagonize mivacurium.

Adolescent↗

The effect of neostigmine on twitch tension and muscle relaxant concentration during infusion of mivacurium or vecuronium.

BACKGROUND: An investigation suggested that neostigmine may not effectively antagonize mivacurium, presumably because neostigmine impairs mivacurium's metabolism. However, the effect of neostigmine on mivacurium's metabolism in vivo has not been reported. Therefore, the effect of neostigmine on neuromuscular function and plasma mivacurium concentrations during constant mivacurium infusion was determined. METHODS: Mivacurium was infused in five patients to maintain 90% depression of adductor pollicis twitch tension, then 50 micrograms/kg intravenous neostigmine was administered without altering the mivacurium infusion. Peak twitch tension after neostigmine, plasma cholinesterase activity, and mivacurium concentrations before and after neostigmine were measured. Five additional patients were given 50 micrograms/kg neostigmine to antagonize block due to continuous infusions of vecuronium. RESULTS: Neostigmine produced less antagonism of mivacurium (39 +/- 11%) than of vecuronium (54 +/- 9%, P < 0.05). Neostigmine decreased plasma cholinesterase activity and increased plasma concentrations of the trans-trans and cis-trans stereoisomers of mivacurium (P < 0.05). CONCLUSIONS: Neostigmine is less effective at antagonizing the neuromuscular effect of mivacurium than that of vecuronium during constant infusion. Neostigmine increases plasma mivacurium concentrations, likely explaining its limited efficacy. Our results confirm that neostigmine impairs the metabolism of mivacurium in vivo and may explain the observation that neostigmine may not effectively antagonize mivacurium-induced block.

Adolescent↗

Atracurium versus vecuronium in asthmatic patients. A blinded, randomized comparison of adverse events.

BACKGROUND: To determine which of atracurium or vecuronium is associated with fewer adverse cardiovascular and pulmonary events in high-risk patients, the authors administered these drugs to patients with known asthma. METHODS: Sixty patients aged 18-75 yr taking bronchodilators chronically for asthma were anesthetized with midazolam, fentanyl, nitrous oxide, and isoflurane; the trachea was intubated without paralysis. When anesthetic conditions and mechanical ventilation were stable, patients were randomly given 0.5 mg/kg atracurium or 0.1 mg/kg vecuronium over 5-10 s, and a blinded observer recorded cardiovascular, pulmonary, and cutaneous signs of adverse reactions for 6 min. RESULTS: Arterial pressures and heart rate decreased after atracurium, and systolic pressure and heart rate decreased with vecuronium; these changes were small in magnitude. Cardiovascular effects (decrease in blood pressure or change in heart rate) > 10% were common with both atracurium (60% of patients) and vecuronium (57%). Cardiovascular effects > 20% were more frequent with atracurium (37%) than with vecuronium (13%, P < 0.05). The incidence of noncardiovascular adverse events (increase in peak airway pressure > 5 cmH2O, tidal volume decrease > 10%, rashes, and wheezing) did not differ between atracurium (17%) and vecuronium (7%). The largest increase in peak airway pressure was 5.1 cmH2O in a patient whose tidal volume decreased 16% with vecuronium; in the remaining patients, tidal volume decreased < 10%. No patients experienced inspiratory wheezing, marked decreases in arterial oxygen saturation, or marked increases in end-tidal carbon dioxide tension. CONCLUSIONS: The authors conclude that, in patients with asthma, adverse cardiovascular events are more common with atracurium than with vecuronium.

Adult↗

Opioid pharmacodynamics in neonatal dogs: differences between morphine and fentanyl.

Clinical experience and laboratory studies suggest that neonates are more sensitive than adults to the ventilatory depressant effects of morphine. Similar sensitivity has been cited, but not demonstrated, for fentanyl. To examine this issue, we determined ventilatory pharmacodynamics of morphine and fentanyl in 28 dogs aged 2-35 days. During isohypercapnia, morphine or fentanyl was infused to depress minute ventilation by > 50% and arterial plasma opioid concentrations were measured. For each drug, an effect compartment pharmacodynamic model was fit to the values for minute ventilation to determine the steady-state opioid plasma concentration depressing ventilation by 50% (C50) and the rate constant for equilibration between plasma concentration and effect (keo). For morphine, there was a marked age-related increase in C50 but no change in keo. For fentanyl, there was a small maturational increase in C50 and no change in keo. We conclude that there are marked maturational changes in the ventilatory depressant effects of morphine resulting from maturational changes in sensitivity rather than in equilibration. Maturational changes in the ventilatory effects of fentanyl are much smaller in magnitude than those for morphine.

Analgesics, Opioid↗