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Biomedical subjects

T J Sullivan

Publications and source records attributed to T J Sullivan.

At least 163 records · Page 9Linked to original sources
PubMed1981

Skin testing to detect penicillin allergy.

Skin testing for penicillin allergy with penicillin G (Pen G), penicilloic acid (PA), and penicilloyl poly-L-lysine (PPL) was performed on 740 subjects, and the results were assessed from epidemiologic and immunologic perspectives. Approximately 95% of these patients had histories of apparent allergic reactions to beta-lactam antibiotics, and 63% were skin-test positive. The prevalence of positive skin tests was related to the time that had elapsed between clinical reactions and skin testing. Ninety-three percent were skin-test positive 7 to 12 mo after reactions, and 22% were positive 10 yr or more after reactions. Patients under 30 yr of age had a prevalence of positive skin tests 1.7-fold higher than older patients. Testing with PPL, PA, and Pen G detected 76.3%, 55.3%, and 57.1% of the positive patients, respectively. Omission of PPL, PA, or Pen G would have led to a failure to detect 25.6%, 7.2%, and 6.2% of the positive patients, respectively. Subjects with skin tests positive to penicillin often reacted to skin tests with other beta-lactam antibiotics; 73% (41 of 56) reacted to ampicillin and 51% (38 of 74) reacted to cephalothin. No serious allergic reactions were provoked by testing. None of the 83 skin test--negative patients treated with beta-lactam antibiotics immediately after testing experienced acute allergic reactions. Two patients developed mild urticaria beginning 3 and 5 days into therapy. One skin test--negative patient experienced urticaria 3 hr after receiving oral penicillin 6 mo after skin testing. This patient's skin-test status immediately before therapy was unknown. These results support the position that testing with PPL, PA, and Pen G is a rapid, safe, and effective method for identifying patients at risk, or not at risk, for allergic reactions to penicillin.

Adolescent↗
PubMed1981

Lipid metabolism during mediator release from mast cells: studies of the role of arachidonic acid metabolism in the control of phospholipid metabolism.

Recent studies indicate that both arachidonic acid (AA) metabolism and phospholipid (PL) metabolism are markedly stimulated during the release of mediators from mast cells. The relationship between stimulated AA metabolism and stimulated PL metabolism in isolated rat mast cells was investigated and then correlated with the secretory process. ETYA (5,8,11,14-eicosatetraynoic acid, a known inhibitor of cyclooxygenase and lipoxygenase pathways of AA metabolism) inhibited 32PO4 incorporation into phosphatidic acid (PA), phosphatidylinositol (PI), and phoshodidylcholine (PC) in both unstimulated mast cells and mast cells stimulated by cross-linking of surface IgE molecules. ID50 values for inhibition of mediator release and of basal and stimulated 32PO4 incorporation into PL were 50 to 60 microM ETYA. Indomethacin (1 to 10 microM) and aspirin (10 to 100 microM) had no significant effect on 32PO4 incorporation or on mediator release. AA (10 microM) inhibited PL labeling in resting mast cells and rendered the cells less responsive to secretory signals. Preincubation of the cells with indomethacin (1 microM) blocked both of these AA effects. When AA was added to stimulated mast cells, however, both PL labeling and mediator release were enhanced. Thus, each of the alterations in AA metabolism caused parallel changes in mast cell PL metabolism and in mediator release. Since both basal and stimulated PL metabolism were modified by ETYA and AA, some form of direct regulation of mast cell PL metabolism by AA metabolites seems likely. The close parallelism of effects on mediator release and on PL metabolism suggests that modulation of mast cell function by AA metabolites may be mediated at lest in part by effects on lipid metabolism.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1980

A package of computer programs designed to simulate pharmacokinetic monitoring of drug therapy.

Three programs are presented which have been developed to simulate conditions encountered in the pharmacokinetic adjustment of dosage regimens. The programs include a drug with one-compartment kinetics, whose elimination is dependent on renal function (gentamicin), a drug with two-compartment kinetics (theophylline), and a drug whose elimination follows non-linear Michaelis-Menten kinetics (phenytoin). The programs may be used as an aid to instruction in clinical pharmacokinetics and to develop and test new methods of pharmacokinetic adjustment of dosage regimens.

Computers↗
PubMed1980

Pharmacological screening of new chemical entities in human subjects and methods of data handling.

1 A system is described for screening new chemical entities in normal human subjects, which is designed to search for novel drug actions at an early stage of drug development. 2 In single (subject) blind experiments, doses are increased incrementally from one subject to next, with immediate feed-back of results from each dose. 3 As many physiological variables as possible are recorded, for which a purpose-designed apparatus system was constructed, and connected to a computer. 4 To overcome problems of inter-subject variability, the need for sensitivity, and to identify drug-related effects from the mass of data generated, a novel data management system was developed, and physiological profiles of volunteer subjects were built up to provide control data. 5 Results from a validation experiment in which isoprenaline was infused intravenously at different rates are presented and discussed.

Dose-Response Relationship, Drug↗
PubMed1980

The effect of proxicromil, a new oral chromone derivative, in antigen challenge tests is asthmatic patients.

Proxicromil is a compound shown in biological tests to have anti-allergic properties. It is well absorbed in humans after oral administration. In order to assess its anti-allergic activity in humans, experiments were carried out in asthmatic patients to investigate its inhibitory effects upon the bronchoconstrictor response to antigen challenge. Two controlled experiments were carried out according to randomized double blind crossover designs, in each of which ten selected patients were pretreated orally with proxicromil before being challenged with inhaled doses of antigen. Inhibition of the immediate response to antigen challenge by single and repeated doses was meaured by intermittent recordings of forced expiratory volume in one second (FEV1) for 30 minutes after challenge. The duration of action of proxicromil and studied by varying the time between administration of the last dose given and inhalation of the antigen. The results showed that proxicromil significantly protected patients against the immediate response to challenge, and possessed a long duration of action of at least 12 hours.

Administration, Oral↗
PubMed1979

Diacylglycerol metabolism in mast cells: a potential role in membrane fusion and arachidonic acid release.

Purified rat peritoneal mast cells stimulated with the polycationic histamine-releasing agent compound 48/80 demonstrated a two- to four-fold increase in cellular levels of 1,2-diacylglycerol (DAG) within 1 min as detected by radioactive labeling and direct quantitation experiments. When 2-[1-14C]arachidonoyl-DAG was incubated in the presence of mast-cell homogenates, a rapid conversion to free arachidonate, and to a lesser extent, to monoacylglycerol, triglyceride, and phospholipid was observed. The release of arachidonate was proportional to the amount of broken-cell preparation added and the time of incubation, was prevented by preheating mast-cell preparations, and did not occur when 1-[1-14C]arachidonoyl-phosphatidylcholine was used as substrate, suggesting that the degradation was mediated by an enzyme with Dag-lipase activity. Although much work remains to be done to clarify the precise role of DAG in mast cells, DAG metabolism may be involved in secretion by generating substances which may faciliate membrane fusion and also in arachidonic acid-derived mediator formation by liberating esterified arachidonic acid from mast-cell lipids. Taken together, these studies indicate that the formation of DAG may play a central role in mast-cell function.

Animals↗
PubMed1979

Smoking and warfarin disposition.

Nine cigarette smokers ingested an average daily 0.032 mg/kg dose of sodium warfarin for 2 wk while continuing to smoke and for an additional 2 wk after having abstained from cigarette smoking for a month washout phase. Steady-state plasma levels of warfarin, clearances, t 1/2, apparent volumes of distribution, steady-state prothrombin times, and plasma thiocyanate levels were measured during both the smoking and nonsmoking phases. During the nonsmoking phase there was a 13% increase in average steady-state warfarin level and a 13% decrease in warfarin clearance rate. There also was a 23% increase in warfarin t 1/2 and an 11% increase in the apparent volume of distribution. Prothrombin time did not change. Thiocyanate levels were 3 to 4 times as high during the smoking than the nonsmoking phase. It appears that cigarette smoking does affect warfarin clearance, t 1/2, and apparent volume of distribution, though the net effect on warfarin's pharmacodynamic activity is negligible, at least at doses which are ineffective therapeutically.

Adult↗