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Biomedical subjects

R B Taylor

Publications and source records attributed to R B Taylor.

At least 73 records · Page 4Linked to original sources

Effect of standard doses of epinephrine on myocardial oxygen delivery and utilization during cardiopulmonary resuscitation.

This preliminary study was conducted to evaluate the effects of 0.02 mg/kg of epinephrine (E) on myocardial blood flow (MBF), myocardial oxygen consumption (MVO2), and delivery (MDO2) when administered during CPR after 10-min cardiopulmonary arrest. Five miniature swine were instrumented for MBF measurements using tracer microspheres. Ventricular fibrillation was induced. After 10 min, CPR was begun with a pneumatic compressor. Measurements of MBF, arterial, and coronary sinus blood gases were made. After 3 min of CPR, each animal received 0.02 mg/kg of E. The measurements were repeated and defibrillation was attempted. During CPR, MDO2 and MVO2 were 0.2 +/- 0.3 and 0.2 +/- 0.3 ml/min/100 g tissue, respectively. The myocardial oxygen extraction ratio (ER) was 94.2 +/- 3.0%. After 0.02 mg/kg of E, MDO2 was 1.1 +/- 1.4, MVO2 was 1.0 +/- 1.3, and ER was 93.9 +/- 0.7% (p greater than .05). There were no successful defibrillations. These data indicate that MDO2 improves slightly during CPR after 0.02 mg/kg of E, but it does not meet the oxygen demands of the fibrillating heart.

Animals↗

Alternative syntheses and related n.m.r. studies of precursors for internal beta-D-galactopyranosyl residues in oligosaccharides, allowing chain extension at O-4.

Crystalline 2,3,6-tri-O-benzoyl-4-O-(bromoacetyl)-alpha-D-galactopyranosyl chloride (5) was prepared from methyl 2,3,6-tri-O-benzoyl-4-O-(bromoacetyl)-alpha- or -beta-D-galactopyranoside by cleavage with dichloromethyl methyl ether (DCMME) in the presence of zinc chloride. Silver trifluoromethanesulfonate (triflate) condensation of 5 with methyl 2,3,6-tri-O-benzoyl-beta-D-galactopyranoside gave the corresponding beta-linked disaccharide, which was O-de(bromoacetyl)ated and the resulting disaccharide nucleophile condensed with 5. The beta-linked trisaccharide obtained was deprotected, to give the methyl beta-glycoside of (1----4)-beta-linked D-galactotriose. Compound 5 was converted in high yield into the corresponding 1-O-beta-acetyl derivative, which was O-de(bromoacetyl)ated with thiourea to afford crystalline 1-O-acetyl-2,3,6-tri-O-benzoyl-beta-D-galactopyranose (9). Condensation of 9 with 5 yielded O-[2,3,6-tri-O-benzoyl-4-O-(bromoacetyl)-beta-D- galactopyranosyl]-(1----4)-1-O-acetyl-2,3,6-tri-O-benzoyl-beta-D- galactopyranose (17), which was cleaved with DCMME to give the corresponding glycosyl chloride (20). The same sequence of reactions involving 1,2,3,6-tetra-O-benzoyl-alpha-D-galactopyranose and 2,3,4,6-tetra-O-benzoyl-alpha-D-galactopyranosyl bromide afforded O-(2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl)-(1----4)-2,3,6-tri-O - benzoyl-alpha-D-galactopyranosyl chloride, which can be used to construct in an oligosaccharide the terminal, beta-linked (1----4)-beta-D-galactobiosyl group. Compounds 5, 17, and 20, when used as glycosyl donors, allow further chain extension at O-4 of the (terminal) beta-D-galactopyranosyl group. The structures of all mono- and di-saccharide intermediates, including those of orthoesters formed during glycosylations under neutral conditions, were confirmed by combination of homo- and hetero-nuclear-correlation n.m.r. experiments. The sites of glycosidic linkages in orthoesters were directly determined by 1 D INAPT n.m.r. experiments. Characteristic features of the 1H- and 13C-n.m.r. spectra of orthoesters which distinguish them from the corresponding oligosaccharides have been summarized.

Carbohydrate Conformation↗

Murine T cells reactive against autologous erythrocytes: evidence for in vitro and in vivo priming with mouse and rat red blood cells.

Normal mice are shown to harbor T cells that can be sensitized to proliferate against autologous red blood cells (RBC). These autoreactive cells were primed in vitro and in vivo with mouse as well as heterologous rat RBC, the in vivo administration of which has been previously shown to trigger the production of auto-RBC antibodies. Two broad classes of specificity are detected following priming: T cells cross-reactive for similar determinants coexpressed by mouse and rat RBC, and T cells specific for antigens restricted to self-RBC. These findings indicate that clonal deletion of self-RBC-reactive T cells is far from complete. The comparison of different in vitro and in vivo immunization protocols revealed the possible existence of several levels of immunoregulatory control which may prevent the expression of autoimmunity by these T cells.

Animals↗

Chromatography of progesterone and its major metabolites in rat plasma using microbore high-performance liquid chromatography columns with conventional injection and detection systems.

A separation of progesterone and its metabolites 17 alpha-hydroxyprogesterone, 20 alpha-hydroxy-4-pregnen-3-one, androstenedione and testosterone by high-performance liquid chromatography with a ternary solvent system is demonstrated. It is found that using a 100 X 1 mm microbore column, higher sensitivity is obtained in the ultraviolet detection of these compounds by using conventionally sized flow cells despite the higher efficiency resulting from the use of a micro-flow cell. It is also shown that, when a non-eluting solvent is used for injection, large injection volumes do not reduce column efficiency, and a 14-fold increase in sensitivity is obtained with a 1-mm column in place of one 4.6 mm in diameter. Using solid-phase extraction and concentration of the sample as pretreatment, progesterone and its hydroxylated metabolites are determined in 0.5-ml samples of rat plasma. The progesterone levels are compared with those obtained by radioimmunoassay.

17-alpha-Hydroxyprogesterone↗

Specific helper T cell reactivity against autologous erythrocytes implies that self tolerance need not depend on clonal deletion.

Using a culture system which supports primary T cell proliferative responses to various antigens we have detected mouse red blood cell (RBC)-reactive T cells in lymphoid tissues from untreated mice. The release of significant amounts of interleukin 2 (IL2) indicates that T helper (or helper/inducer) cells are activated by stimulation with RBC. Upon restimulation in vitro these cells proliferate specifically against mouse RBC with the kinetics and magnitude characteristic of a secondary response. Since autologous RBC are tolerated in vivo in spite of the presence of such specifically reactive T helper cells, these findings imply that self tolerance, even to certain nonsequestered antigens, may depend largely on regulatory mechanisms rather than on clonal deletion or inactivation.

Animals↗

Partial characterization of two (Ca+2 + Mg+2)-dependent ATPase activities from bovine brain synaptic membrane homogenates.

Synaptic plasma membranes isolated from bovine brain exhibited a low and high affinity (Ca+2 + Mg+2)-dependent ATPase as evidenced by kinetic constants for ATP. One activity which hydrolyzed ATP maximally at pH 7.4 and 7.8 exhibited an 8-fold higher affinity when compared to the second or lower affinity activity which hydrolyzed ATP maximally at pH 7.0. Both activities exhibited submicromolar kinetic constants for Ca+2 (Km = 0.24 micromolar). Km values for magnesium differed significantly; the lower affinity activity being approximately 6.5 times higher (120 microM) than that observed for the high affinity activity (18 microM). Vmax values obtained under optimal assay conditions (low and high) were 110-135 and 43-55 nmol/min/mg protein, respectively. Both activities were KCN, NaN3 and ruthenium red insensitive. Only slight inhibition was observed in the presence of rotenone and oligomycin. Although both activities were observed to be trifluoperazine sensitive, they differed significantly with regard to other parameters. Na+1 and NH4+1 ions preferentially inhibited the low affinity activity greater than 90%. Cs+1 ions completely inhibited the high affinity activity while reducing the low affinity only 22%. Li+1, Al+3 and Mn+2 significantly inhibited the high affinity activity while reducing the low activity only moderately. Both the low and high activity were inhibited by vanadate with half maximum inhibition occurring at 2 and 5 microM, respectively indicating the plasma membrane origin of these activities. Thermal denaturation studies indicated the high affinity activity to be stable for 2 minutes at 45 degrees C after which 50% of the activity is lost at 2.5 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A critical appraisal of drug stability testing methods.

The determination of potency or shelf life, impurity limit testing, and study of reaction mechanisms are considered as different aspects of drug stability. These aspects traditionally have been treated in isolation. The current criterion for a stability-indicating assay is criticized and the merits of choosing reactant or decomposition product for monitoring decomposition are discussed. The initial-rate method of determining reaction order and rate constants by analysis of decomposition product is described and its potential advantages over traditional integral methods are discussed. Examples of the application of the initial-rate method to simple and complex drug decomposition systems for the determination of decomposition rate constants are given. Applications to limit testing and study of reaction mechanisms are outlined and the dependence of the initial-rate method and decomposition product analysis on modern chromatographic methods is emphasized.

Drug Stability↗

Single dose pharmacokinetics of proguanil and its metabolites in healthy subjects.

1. Plasma and whole blood concentrations of proguanil and its two major metabolites cycloguanil (CG) and 4-chlorophenylbiguanide (CPB) were measured by a sensitive h.p.l.c. technique in nine healthy adult male volunteers after a single oral dose of proguanil 200 mg. 2. Proguanil was absorbed with a median time to peak plasma concentration of 3 h (range 2-4 h). 3. Peak plasma concentrations of proguanil ranged between 150 and 220 (median 170) ng ml-1 compared with 12 to 69 (median 41) ng ml-1 for the active antimalarial metabolite CG, and 3 to 16 (median 11) ng ml-1 for CPB. Peak (mean +/- s.d.) plasma CG concentrations occurred 5.3 +/- 0.9 h and peak CPB concentrations occurred 6.3 +/- 1.4 h after oral administration of proguanil. 4. Whole blood concentrations of proguanil were approximately five times higher, and whole blood CPB concentrations were four times higher than corresponding plasma values, whereas plasma and whole blood concentrations of CG were similar. 5. A triexponential function was fitted to these data; mean (+/- s.d.) values for the AUC were 3046 +/- 313 ng ml-1 h for proguanil, 679 +/- 372 ng ml-1 h for CG and 257 +/- 155 ng ml-1 h for CPB. 6. Plasma and whole blood concentrations of proguanil and its metabolites declined in parallel with terminal elimination half-lives estimated as 16.1 +/- 2.9 h and 15.7 +/- 2.4 h, respectively. Mean residence times in plasma and whole blood were estimated as 21.2 +/- 4.9 and 19.3 +/- 2.4 h.

Adult↗

Esophageal foreign bodies.

Over 80 per cent of ingested foreign bodies pass through the gastrointestinal tract without incident. Sharp (bones, pins, needles, wire) or long (greater than 6.5 cm) foreign bodies are most commonly implicated in perforation. Food boluses are most common in obstruction seen in adult patients and associated esophageal pathology is common in patients aged 60 years and older. Adults with nonfood foreign bodies have a high incidence of psychiatric, social, or chemical derangements. Pediatric patients most commonly ingest coins. Ingestions tend to occur during nonschool months or in high-risk situations, and repeat ingestions are not uncommon. Fatalities and other major complications are linked to type of foreign body, location, and duration of the impaction. Deaths have also occurred with endoscopic and enzymatic modalities of treatment. Glucagon and Foley catheter removal are safe techniques in selected patients, provided resuscitative skill and equipment are available. Based on these data, an algorithmic approach to the management of esophageal foreign bodies by the emergency physician is recommended (Table 5).

Adult↗

Development of a stability-indicating assay for nafimidone [1-(2-naphthoylmethyl)imidazole hydrochloride] by high-performance liquid chromatography.

The rational development of a stability-indicating assay for nafimidone [1-(2-naphthoylmethyl)imidazole hydrochloride] is demonstrated. It allows resolution of the decomposition products, obtained both on melting and resulting from decomposition in solution. Ion-pair chromatography was used to elute the solution decomposition products before the parent compound, thus producing maximum sensitivity of detection of these in the presence of undecomposed reactant. Stability data in terms of first-order rate constants were obtained in two different buffer solutions both from conventional integrated-rate equations using reactant concentration measurements, and by the initial rate method using decomposition product concentrations. In the light of this investigation, additional criteria for stability-indicating assays are suggested, which exploit the sensitivity as well as specificity of high-performance liquid chromatography.

Chromatography, High Pressure Liquid↗

Emergency evaluation and treatment of headache.

This article presents a practical approach to the problem of headache in the emergency setting, including a simplified method of diagnosis and a discussion of the major types of headache. Emphasis is placed on differentiating headaches caused by serious illnesses from the primary headache syndromes.

Analgesics↗