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Biomedical subjects

J M Bailey

Publications and source records attributed to J M Bailey.

At least 91 records · Page 5Linked to original sources
PubMed1994

Pharmacokinetics of aprotinin in preoperative cardiac surgical patients.

BACKGROUND: Aprotinin, a polypeptide protease inhibitor, reduces bleeding and transfusion requirements during cardiac surgery. To investigate aprotinin's pharmacokinetics, we administered therapeutic doses to patients scheduled to undergo cardiac surgery. METHODS: Preoperative doses of 500,000 and 1,000,000 kallikrein inhibitor units (KIU) were administered as an infusion over 30 min to 28 patients, and plasma concentrations were measured for 48 h. Aprotinin concentrations were determined using a sandwich-enzyme-linked immunosorbent assay. A three-compartment model was fit to the measured aprotinin concentrations using extended nonlinear least-squares regression. RESULTS: Plasma aprotinin concentrations at the end of the 30-min infusion were 147 +/- 61 KIU/ml for the 1,000,000-KIU dose and 60 +/- 19 KIU/ml for the 500,000-KIU dose. Elimination clearance was 35.5 ml/min, and volume of distribution at steady state was 26.5 l. CONCLUSIONS: A 2,000,000-KIU dose is needed to produce the plasma concentration of 200 KIU/ml associated with kallikrein inhibition. Plasma concentrations in excess of 50 KIU/ml, the concentration required to inhibit plasmin, can be achieved by a significantly smaller dose. Based on the derived pharmacokinetic parameters, an infusion model was developed to appropriately administer and maintain effective plasma concentrations of aprotinin, depending on the plasma concentration desired and the target proteases to be inhibited.

Aged↗
PubMed1994

Pharmacokinetics of intravenous milrinone in patients undergoing cardiac surgery.

BACKGROUND: Milrinone is a phosphodiesterase inhibitor with positive inotropic and vasodilator effects that are useful in the treatment of ventricular dysfunction after cardiac surgery. However, the pharmacokinetics of the drug have been investigated only in healthy volunteers and in patients with chronic congestive heart failure. This study investigates the pharmacokinetics of milrinone in adult cardiac surgical patients after cardiopulmonary bypass. METHODS: Milrinone was administered to 25 patients just before or immediately after separation from cardiopulmonary bypass. Arterial blood was sampled over the next 16 h and milrinone plasma concentrations were determined by high-performance liquid chromatography. Data were analyzed by extended nonlinear least-squares regression. The relation between milrinone plasma concentration and hemodynamic effect was examined in an additional 11 patients who had cardiac indices less than 2.5 l.min-1.m-2 immediately after separation from cardiopulmonary bypass. Milrinone was administered and plasma concentrations were related to changes in cardiac index during the next 10 min. RESULTS: A milrinone dose of 50 micrograms/kg in conjunction with an infusion of 0.5 micrograms.kg-1.min-1 consistently maintained plasma concentrations in excess of 100 ng/ml. A triexponential equation describing the plasma concentration as a function of time was used to describe the data. Central-compartment volume was 102 ml/kg, volume of distribution was 1,698 ml/kg, and elimination clearance was 1.88 ml.kg-1.min-1. Pharmacokinetic parameters were independent of dose. The relation between plasma concentration and percentage increase in cardiac index could be described by a sigmoidal curve with the plasma concentration associated with a 50% increase in cardiac index equal to 167 ng/ml. CONCLUSIONS: A milrinone dose of 50 micrograms/kg with an infusion at 0.5 micrograms.kg-1.min-1 maintains plasma concentrations at or above the threshold of therapeutic effects.

Aged↗
PubMed1994

Amrinone: its effect on vascular resistance and capacitance in human subjects.

Reports evaluating amrinone's effects in normal (intact) human subjects are complex and difficult to interpret because of the drug's diverse effects on myocardial function, resistance vessels, and vascular capacitance. In this study, 1.5 mg/kg of amrinone was administered as an intravenous bolus to cardiac surgical patients during constant flow cardiopulmonary bypass to determine its isolated effects on venous capacitance and vascular resistance. We noted a significant decrease in vascular resistance up to 8 min after injection and a 460 +/- 160 ml (mean +/- SD) decrease in venous reservoir volume 10 min after injection. Amrinone has potent venous and arterial vasodilating properties that make it a unique drug for treating congestive heart failure in addition to its reported positive inotropic effects.

Amrinone↗
PubMed1993

Compact protein sequencer for the C-terminal sequence analysis of peptides and proteins.

We describe the construction of a compact protein sequencer designed specifically for the C-terminal sequence analysis of peptides and proteins. This sequencer has a vertical flow path and is equipped with a continuous flow reactor (CFR). The flow paths for the various reagents and solvents have been minimized. A unique feature of this instrument is the design of a quadrate valve (quad valve) which permits the delivery of four solvents or reagents to the conversion flask (CF). Combination of two of these quad valves in series permits the delivery of eight solvents and reagents to the CFR. The CF contains three inputs from the top, one for transfer of the contents of the CFR, one which is used as a vent, and one for input of solvents or reagents from the CF quad valve. The CF drains from the bottom, connecting to a switching valve which allows delivery either to a waste bottle or to an on-line HPLC. Another unique feature of this instrument is the design of an optical flow detector which permits injection of approximately 90% of the contents of the CF for HPLC analysis. The overall size of the instrument (11 w x 16.5 h x 23.5 d in.) is smaller than commercially available instruments for protein sequencing and represents the first time an instrument has been constructed specifically for C-terminal sequence analysis. The utility of this instrument is demonstrated with the C-terminal sequence analysis of protein samples noncovalently applied to Zitex strips and with a peptide covalently attached to carboxylic acid-modified polyethylene film.

Amino Acids↗
PubMed1993

Heritable factors influence sexual orientation in women.

Homosexual female probands with monozygotic cotwins, dizygotic cotwins, or adoptive sisters were recruited using homophile publications. Sexual orientation of relatives was assessed either by asking relatives directly, or, when this was impossible, by asking the probands. Of the relatives whose sexual orientation could be confidently rated, 34 (48%) of 71 monozygotic cotwins, six (16%) of 37 dizygotic cotwins, and two (6%) of 35 adoptive sisters were homosexual. Probands also reported 10 (14%) nontwin biologic sisters to be homosexual, although those sisters were not contacted to confirm their orientations. Heritabilities were significant using a wide range of assumptions about both the base rate of homosexuality in the population and ascertainment bias. The likelihood that a monozygotic cotwin would also be homosexual was unrelated to measured characteristics of the proband such as self-reported history of childhood gender nonconformity. Concordant monozygotic twins reported similar levels of childhood gender nonconformity.

Adoption↗
PubMed1993

Studies in C-terminal sequencing: new reagents for the synthesis of peptidylthiohydantoins.

In previous studies aimed at the sequencing of peptides and proteins from the carboxy terminus, we have derivatized the C-terminus to a thiohydantoin using acetic anhydride and trimethylsilylisothiocyanate (TMS-ITC) and subsequently hydrolyzed it to form a shortened peptide capable of further degradation and an amino acid thiohydantoin which can be identified by reverse-phase HPLC. Current limitations to this chemistry include an inability to derivatize proline and low yields with asparagine and aspartic acid residues (Bailey et al., 1992). In an attempt to solve some of these problems, we have investigated the use of reagents other than acetic anhydride for the activation of the C-terminal carboxylic acid. These include 2-fluoro-1-methylpyridinium tosylate, 2-chloro-1-methylpyridinium iodide, and acetyl chloride. Addition of TMS-ITC to peptides activated by the 2-halo-pyridinium salts formed the expected peptidylthiohydantoin, but in addition formed a peptide chemically modified at the C-terminus which was blocked to C-terminal sequence analysis. This derivative was not obtained when either acetic anhydride or acetyl chloride was used for activation. Formation of this derivative was found to require the presence of an isothiocyanate reagent in addition to the halo-pyridinium salt. Sodium thiocyanate, TMS-ITC, and a new reagent for thiohydantoin synthesis, tributyltinisothiocyanate (TBSn-ITC), were all found to be capable of forming this analogue. Structural elucidation of the C-terminally modified amino acid revealed it to be a 2-imino-pyridinium analogue. Formation of this C-terminally blocked peptide could be minimized by the use of the 2-chloro-pyridinium reagent, rather than the 2-fluoro reagent, and by performing the reaction at a temperature of 50 degrees C or lower. The 2-halo-pyridinium reagents offer potential advantages over the use of acetic anhydride for activation of the C-terminal carboxylic acid. These include: milder reaction conditions, faster reaction times, and the ability to sequence through C-terminal aspartic acid. The TBSn-ITC reagent was found to be comparable to TMS-ITC for formation of peptidylthiohydantoins.

Acetic Anhydrides↗
PubMed1993

Familiality of female and male homosexuality.

We examined data from a large cohort of homosexual and heterosexual females and males concerning their siblings' sexual orientations. As in previous studies, both male and female homosexuality were familial. Homosexual females had an excess of homosexual brothers compared to heterosexual subjects, thus providing evidence that similar familial factors influence both male and female homosexuality. Furthermore, despite the large sample size, homosexual females and males did not differ significantly from each other in their proportions of either homosexual sisters or homosexual brothers. Thus, results were most consistent with the possibility that similar familial factors influence male and female sexual orientation. However, because results conflicted with those of some other studies, and because siblings' sexual orientations were obtained in a manner likely to yield more errors than in these other, smaller studies, further work is needed using large samples and more careful methods before the degree of cofamiliality of male and female homosexuality can be resolved definitively. We also examined whether some parental influences comprised shared environmental effects on sexual orientation. Scales attempting to measure such influences failed to distinguish subjects with homosexual siblings from subjects with only heterosexual siblings and, thus, did not appear to measure shared environmental determinants of sexual orientation.

Adult↗
PubMed1993

Maternally rated childhood gender nonconformity in homosexuals and heterosexuals.

Homosexual and heterosexual subjects provided self-ratings of childhood gender nonconformity. Additionally, their mother rated them on several adjectives describing childhood behavior, which included words related to gender nonconformity. Male homosexuals were remembered by their mothers as less masculine and more nonathletic. This finding did not appear to be due to a bias in mothers' memories. Though female homosexuals were recalled as more masculine than female heterosexuals, this appeared to reflect retrospective bias, as mothers who knew of their daughters' homosexuality were more likely to rate them as masculine. Both self-rated and maternally rated childhood gender nonconformity made independent contributions in predicting sexual orientation. Within the homosexual samples, maternal and self-ratings of subjects' childhood gender nonconformity failed to correlate significantly.

Adolescent↗
PubMed1993

A technique for approximately maintaining constant plasma levels of intravenous drugs.

BACKGROUND: There is increasing interest among anesthesiologists in the use of continuous infusion of intravenous drugs. The therapeutic effect of most drugs is a function of the concentration at the site of drug effect, which in turn is determined by the plasma concentration. Constant plasma concentrations can be maintained by computer-controlled infusion pumps. However, such equipment is not yet widely available and will be expensive. METHODS: A technique is presented to enable the anesthesiologist to maintain approximately a desired plasma concentration after an arbitrary bolus dose by using a series of infusions with rates decreasing in a stepwise fashion. The algorithm is based on approximating the exact infusion needed to maintain the target plasma concentration by producing this concentration at discrete, specific times. Equations are derived for calculating the sequential rates of the infusion scheme. The equations assume linear pharmacokinetics, and the starting point for derivation of the equations is the assumption that the plasma concentration is given by the convolution of the drug infusion and the unit dose-response function. RESULTS: The accuracy of the technique was assessed by simulating the infusion of fentanyl and midazolam. By using an infusion scheme of three steps, the error was no greater than 38% for fentanyl and no greater than 10% for midazolam. CONCLUSIONS: Other than the assumption of linear kinetics, the algorithm is independent of pharmacokinetic models. Implementation does not require computer-based numerical analysis.

Algorithms↗
PubMed1993

Familial aggregation of female sexual orientation.

OBJECTIVE: The purpose of this study was to determine whether female homosexuality is familial and whether it is cofamilial with male homosexuality. METHOD: Subjects included 84 homosexual and 79 heterosexual female probands recruited through newspaper advertisements. Probands were asked about their siblings' sexual orientations and were asked for permission to contact siblings to confirm their reports. RESULTS: The authors were able to contact 60% of eligible siblings, and the information they provided about their sexual orientations confirmed that probands' reports were highly accurate. Homosexual probands had a significantly higher proportion of homosexual sisters according to four criteria for rating siblings' sexual orientations. Homosexual probands also had a higher proportion of homosexual brothers; however, this difference was not significant. CONCLUSIONS: Female homosexuality appears to be familial. Further research is required to resolve the question of whether female and male homosexuality are cofamilial.

Adult↗