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Biomedical subjects

J A Bennett

Publications and source records attributed to J A Bennett.

At least 55 records · Page 3Linked to original sources
PubMed1996

Activated coagulation time: one tube or two?

OBJECTIVES: To compare activated coagulation time (ACT) management directed by a single ACT determination to that of the average of two simultaneously obtained ACT values. DESIGN: Prospective study. SETTING: Cardiac operating rooms of a university hospital. PARTICIPANTS: Patients undergoing surgery requiring cardiopulmonary bypass. INTERVENTIONS: All ACT determinations were performed in duplicate; patients were managed based on the average of the duplicate values, as is customary. Results of all tests were recorded on a spreadsheet, and the management dictated by a randomly chosen single result of each pair was compared with the management directed by the average value of each pair. Predetermined criteria were set for preference of one testing method over the other. Patients were grouped according to preoperative heparin exposure, and results of the two groups were compared. MEASUREMENTS AND MAIN RESULTS: One hundred patients underwent 683 paired celite ACT determinations. In 565/683 tests (83%), both methods called for identical heparin management responses. Management by the single-tube method would have resulted in supplemental heparin administration 34% more often than management by the average method. The single-tube method would have resulted in withholding supplemental heparin 13 times when the average method called for supplemental heparin administration, a 16% occurrence. The results of the patients with and without preoperative heparin exposure were not significantly different. CONCLUSIONS: The results of this study suggest the use of a two-tube average method to guide heparin administration for cardiopulmonary bypass. Preoperative heparin exposure did not influence this outcome.

Cardiopulmonary Bypass↗
PubMed1996

Thrombin receptor-related hemostatic defect after cardiopulmonary bypass.

Platelet abnormalities have been blamed for the hemostatic defect that develops after cardiopulmonary bypass (CPB), but investigators have not been able to agree upon an intrinsic platelet abnormality responsible for the observed defect. To better define the blood components responsible for this post-operative hemostatic defect, we compared platelet function in whole blood (WB) to that in platelet-rich plasma (PRP) in 33 patients undergoing coronary artery bypass grafting. We measured platelet aggregation in response to various platelet agonists, including thrombin and TRAP-6 (a 6-amino acid peptide that activates the thrombin "tethered ligand" receptor site). In WB there was a lasting, diminished response to TRAP-6, but not to gamma-thrombin, after CPB. Control experiments showed that this diminished response to TRAP-6: (1) was not related to heparin or heparin-protamine complexes, (2) was not the result of hemodilution during CPB, (3) was not related to increased amounts of naturally occurring enzymes (aminopeptidases) that degrade TRAP, and (4) was not able to be reversed by the addition of as much as a 10-fold excess of the usual TRAP-6 aggregating dose to WB preparations. In contrast, no corresponding defect in platelet aggregation could be identified in PRP obtained from patients after CPB. These results show that, in post-operative blood samples, blood components present in WB and not in PRP (eg, red blood cells, activated white cells or platelets bound to white cells) diminish the ability of TRAP peptides to activate the thrombin receptor but do not decrease the ability of gamma-thrombin to induce platelet aggregation. This suggests that for circulating platelets after CPB: (1) interactions of platelets with other blood cell elements are the cause of altered postoperative platelet reactivity rather than any intrinsic CPB-induced platelet defect, (2) drugs, such as aprotinin, that limit activation of white cells and the fibrinolytic system may also have beneficial effects on platelet function after CPB, and (3) alternate mechanisms exist that allow thrombin, but not TRAP-6, to activate platelets normally after CPB (perhaps a second, as yet undefined, thrombin receptor).

Cardiopulmonary Bypass↗
PubMed1996

Human CD8 alpha expression in NK cells but not cytotoxic T cells of transgenic mice.

In our previous work, DNase hypersensitivity mapping was used to identify an enhancer within the human CD8 alpha (hCD8 alpha) gene which allowed T cell-specific expression of a reporter construct in transiently transfected cell lines. To study the role of this intronic enhancer in vivo, transgenic mice were made using human CD8 genomic constructs. We found that while a 14 kb wild-type human CD8 alpha (WThCD8) genomic construct did not lead to expression in mature peripheral CD8+ T cells, this transgene was consistently expressed in small populations of T cells and B cells, and in a subset of mouse NK cells. While murine CD8 is not normally expressed on resting NK cells, expression of the human CD8 transgene on mouse NK cells is appropriate since CD8 is expressed on a subset of human NK cells. Deletion of the intronic enhancer resulted in a complete loss of transgene expression in most lines and a loss of expression only in NK cells in one line. Our results indicate, firstly, that cis-acting sequences within the 14 kb genomic fragment are sufficient for NK cell-specific expression. In addition, our results suggest that the enhancer may have dual roles in regulation of transgene expression. It may enhance general expression of the transgene and may also be required for NK cell-specific expression.

Animals↗
PubMed1996

Upper airway closure: a primary source of difficult ventilation with sufentanil induction of anesthesia.

Large-dose opioid induction of anesthesia can lead to difficult ventilation via a mask. Poor ventilatory compliance (VC) may be secondary to "rigid" chest and abdominal wall musculature, glottic closure, or upper airway obstruction. This double-blind study assessed the contribution of the upper airway to poor VC by inducing sufentanil anesthesia in patients undergoing cardiac surgery who are ventilated via a mask (Group M) or endotracheal tube fiberoptically inserted (Group E). After induction of anesthesia with sufentanil 3 microgram/kg from time (T) = 0 min to T = 2 in Group M (n = 17) or Group E(n = 23), VC and adductor pollicis (AP) twitch tension was measured continuously. Immediately prior to muscle relaxant (pipecuronium or doxacurium) administration at T = 3, Group E demonstrated significantly better VC (46 mL/cm H2O [39-55 interquartile range (IQR)]) than Group M (19 mL/cm H2O [7-24 IQR]). The effect of muscle relaxant administration on VC preceded its effect at the AP. After complete relaxation of the AP at T = 9, both groups had similar VC. Difficult ventilation during sufentanil induction of anesthesia lies at the level of the glottis or above. Bypassing these structures with an endotracheal tube overcomes the usual decreased VC.

Aged↗
PubMed1996

Effect of regular terbutaline on the airway response to inhaled budesonide.

BACKGROUND: The rebound increase in bronchial reactivity and fall in forced expiratory volume in one second (FEV1) following treatment with beta agonists seen in several studies has occurred regardless of concurrent steroid therapy. Little is known about the effect of adding beta agonists to corticosteroids, but in a recent study regular treatment with terbutaline appeared to reduce some of the beneficial effects of budesonide. The effects of budesonide alone and in combination with regular terbutaline treatment on lung function, symptom scores, and bronchial reactivity were therefore examined. METHODS: Sixteen subjects with mild stable asthma inhaled budesonide 800 micrograms twice daily for two periods of 14 days with terbutaline 1000 micrograms three times daily or placebo in a double blind crossover fashion. FEV1 and the dose of histamine or adenosine monophosphate (AMP) causing a 20% fall in FEV1 (PD20) were measured before and 12 hours after the final dose of treatment, and changes from baseline were compared. Seven day mean values for daily morning and evening peak expiratory flow (PEF) values, symptom scores, and rescue medication were compared before and during treatment. RESULTS: Morning and evening PEF rose more with budesonide plus terbutaline than with budesonide alone, with a mean difference of 19 l/min occurring in the evening (95% confidence interval (CI) 2 to 36). There was no difference in symptom scores during treatment. Following treatment the mean increase in FEV1 was 150 ml higher with budesonide alone (95% CI-10 to 300). There was no difference between treatments in change in histamine and AMP PD20. CONCLUSIONS: Evening PEF was greater when budesonide was combined with regular terbutaline. There was no evidence of a difference in bronchial reactivity following the two treatment regimens. The findings of a previous study were not confirmed as the reduction in FEV1 after budesonide and terbutaline was smaller and not statistically significant. Further work is needed to determine whether this disparity in findings in the two studies is due to a type 2 statistical error in this study or a spurious finding in the previous study.

Adrenergic beta-Agonists↗
PubMed1996

Effect of cessation of short-term therapy with ipratropium bromide on lung function and airway responsiveness.

Regular exposure to antimuscarinic drugs would be expected to upregulate airway muscarinic receptors and could cause a transient increase in airways obstruction if treatment was stopped or omitted. We have examined peak expiratory flow rate (PEFR) during treatment and forced expiratory flow in one second (FEV1) and airway responsiveness to three constrictor agonists (as the provocative dose of agonist causing a 20% fall in FEV1, (PD20)) following cessation of regular inhaled ipratropium bromide, in 13 subjects with mild stable asthma. Subjects inhaled placebo and ipratropium bromide, 80 microg q.i.d. for 14 days in a cross-over fashion with a 1 week run-in/wash-out period before and after each treatment period. Subjects recorded symptom scores and PEFR throughout the study, and FEV1 and PD20 to histamine, methacholine and metabisulphite were measured before and after cessation of treatment. When compared to baseline, FEV1 was lower after cessation of ipratropium than after placebo, with a significant difference 30 h after the last dose (difference 190 mL; 95% confidence interval (95% CI) 310-70 mL; p<0.02). FEV1 measured 6-10 days later, did not differ significantly. PEFR was significantly lower after cessation of ipratropium than after placebo on Day 15 (19-37 h after the last dose) (mean difference 4.6%; 95% CI 1.6-7.5%; p<0.01) but not on Day 16. There were no significant changes in PD20 histamine, methacholine and metabisulphite, symptom scores or rescue bronchodilator use after cessation of treatment. Thus, transient bronchoconstriction was found around 30 h after cessation of regular therapy with inhaled ipratropium for 2 weeks. The mechanism is unclear, as no evidence of muscarinic receptor upregulation was found. Although the changes were small and unlikely to be important for most patients, the results of this study indicate that the timing of lung function measurements relative to the last dose of ipratropium is important when interpreting the course of lung function in long-term studies.

Administration, Inhalation↗
PubMed1996

A target-dose finding study of clozapine in patients with schizophrenia.

Evidence from recent studies suggests that clozapine plasma concentrations greater than 350 ng/ml are correlated with therapeutic response. However, little is known about the clozapine dosages required to achieve these plasma concentrations. The purpose of this study was to determine if a target dose of 6 mg/kg/day of clozapine would produce a steady state plasma concentration of > 350 ng/ml. Twelve patients with schizophrenia by DSM-III-R criteria who were refractory to treatment with standard antipsychotics were treated with clozapine utilizing a 10- to 14-day titration to a target dose of 6 mg/kg/day. The mean (+/- SD) clozapine plasma concentration achieved after 5 days at the target dose was 584 +/- 417 ng/ml. Thus, although the target dose successfully produced therapeutic plasma concentrations for most patients, a wide variation was also apparent.

Adult↗
PubMed1996

A randomized comparison of divalproex oral loading versus haloperidol in the initial treatment of acute psychotic mania.

BACKGROUND: Uncontrolled evidence suggests that divalproex administered via the oral loading strategy of 20 mg/kg/day may produce clinically significant antimanic response within 3 days of treatment in some patients. We conducted a prospective study to compare the antimanic response of divalproex oral loading with that of haloperidol in the initial treatment of acute psychotic mania. METHOD: After a < or = 1-day screening period, 36 consecutive hospitalized patients with bipolar disorder, manic or mixed phase and with psychotic features, were randomly assigned to receive either divalproex 20 mg/kg/day or haloperidol 0.2 mg/kg/day for 6 full days, without other psychotropic agents except lorazepam up to 4 mg/day for management of agitation. Serum valproate concentrations were measured after 1 day of treatment. Response was measured daily by a blind rater using the Young Mania Rating Scale and the Scale for Assessment of Positive Symptoms. RESULTS: Divalproex oral loading and haloperidol were equally effective in acutely reducing manic and psychotic symptoms. The greatest rate of improvement for both drug regimens occurred over the first 3 full days of treatment. Side effects were infrequent and minor for both treatments, except for extrapyramidal side effects which were significantly more common with haloperidol. CONCLUSION: Divalproex oral loading may produce rapid onset of antimanic and antipsychotic response comparable to that of haloperidol and with minimal side effects in the initial treatment of acute psychotic mania in a subset of bipolar patients.

Acute Disease↗
PubMed1996

A pharmacoeconomic model of divalproex vs. lithium in the acute and prophylactic treatment of bipolar I disorder.

BACKGROUND: Divalproex and lithium are the two most rigorously studied pharmacologic treatments for acute mania in bipolar I disorder in randomized, controlled trials. The differences between the drugs in their time course of onset, predictors of response, and side effects have potentially important pharmacoeconomic implications. METHOD: Utilizing data from published studies, the University of Cincinnati Mania Project, and a consensus panel of psychiatrists, we developed a decision-analytic model to estimate the costs of treating patients with bipolar I disorder, acutely and prophylactically, for 1 year with divalproex or lithium. RESULTS: In the overall group of patients with bipolar I disorder, initial treatment with divalproex led to costs that were 9% lower than costs for initial treatment with lithium. Cost savings associated with divalproex were greatest for patients with mixed mania and rapid cycling, whereas cost savings for patients with classic mania were greater for lithium. CONCLUSION: According to the decision-analytic model developed in this study, divalproex, possibly because of a more rapid rate of antimanic activity associated with oral loading, is a less costly treatment than lithium in the acute and prophylactic treatment of patients with bipolar I disorder over 1 year.

Acute Disease↗
PubMed1996

Factors associated with pharmacologic noncompliance in patients with mania.

BACKGROUND: Studies of noncompliance with pharmacotherapy in bipolar disorder have primarily involved outpatients receiving lithium. There are limited data to date regarding the rates of noncompliance in patients with bipolar disorder and schizoaffective disorder hospitalized for recurrent mania. Similarly, the influence of race, illness phenomenology, and comorbid psychiatric and medical disorders and the treatment with antipsychotics, antidepressants, and mood-stabilizing agents other than lithium on noncompliance in this population have not been systematically examined. METHOD: Patients hospitalized for acute mania (N = 101) were evaluated by the Structured Clinical Interview for DSM-III-R to establish diagnosis and comorbidity and the Young Mania Rating Scale and Hamilton Rating Scale for Depression to assess severity of manic and depressive symptoms, respectively. Compliance was assessed by responses to a clinician-administered questionnaire administered to the patient, treaters, and significant others and by admission plasma concentrations of mood-stabilizing agents. RESULTS: Sixty-five patients (64%) were noncompliant with their pharmacologic regimen in the month prior to admission as defined by criteria for full compliance and partial or total noncompliance. Noncompliance was significantly associated with greater severity of mania upon admission (p = .02) and treatment with combinations of mood stabilizers (p = .01). CONCLUSION: Noncompliance with pharmacotherapy was present in the majority of patients admitted for acute mania and was associated with greater severity of mania upon admission and treatment with combinations of mood stabilizers.

Acute Disease↗
PubMed1996

Health-economic implications of the onset of action of antimanic agents.

BACKGROUND: Three medications, lithium, valproate, and carbamazepine, have been shown to be effective in the treatment of acute mania in randomized, controlled clinical trials. Additional research over the past decade has provided data regarding potential differences between these medications according to their time course of onset and clinical predictors of response in acute mania. These differences have potential impact on both the choice of medication and the health-economics of the treatment of acute mania. METHOD: Published reports regarding the time course of onset, clinical factors associated with response, and health-economic impact of the treatment of acute mania with lithium, valproate, and carbamazepine were reviewed (PAPERCHASE data base, 1966 to present, terms: bipolar disorder, drug treatment, lithium, valproate, and carbamazepine). RESULTS: Valproate, when administered via an oral loading dosage, may have a more rapid onset of action than lithium and carbamazepine. Preliminary data suggest that specific clinical factors associated with response differ between the three medications. Health-economic studies suggest that treatment of acute mania with valproate may be associated with greater cost savings due to shorter lengths of hospital stay, particularly in patients with mixed mania and rapid cycling. Patients treated with the combination of carbamazepine and lithium also had reduced hospital lengths-of-stay in one study. Lithium may have greater cost savings in patients with classic mania. CONCLUSION: Preliminary data from studies reviewed suggest that important differences exist between lithium, valproate, and carbamazepine in their time course of onset and factors associated with response in the treatment of patients with acute mania. These differences may also impact the cost savings associated with treatment with these agents.

Bipolar Disorder↗
PubMed1995

Topology profile for a glutamate receptor: three transmembrane domains and a channel-lining reentrant membrane loop.

We investigated the transmembrane topology of the GluR3 subunit that was translated in rabbit reticulocytes supplemented with microsomal membranes. A prolactin reporter epitope was fused to GluR3 at six locations, bracketing each of the proposed transmembrane domains. The sidedness of the epitope in the microsomal membrane was then assessed by proteinase K sensitivity. The N terminus and the entire region between M3 and M4 was extracellular, and the C terminus was intracellular by this method. Four native N-linked glycosylation sites in the amino terminus and one introduced site between M3 and M4 were utilized, confirming the extracellular location of these regions. Epitopes inserted upstream and downstream of M2 were protease sensitive and thus intracellular. Our results support a topological model for glutamate receptor subunits that consists of three transmembrane domains, M1, M3, and M4, and another domain, the proposed channel-lining M2, which forms a reentrant membrane segment with both ends facing the cytoplasm.

Animals↗
PubMed1995

Desflurane controls the hemodynamic response to surgical stimulation more rapidly than isoflurane.

STUDY OBJECTIVE: To compare the control of hemodynamic response to surgical stimulus of desflurane to that of isoflurane. DESIGN: Prospective randomized study. SETTING: Operating room of a major U.S. teaching hospital. PATIENTS: 59 ASA status I, II, and III patients 18 to 80 years of age and were undergoing orthopedic or intra-abdominal surgical procedures of 1 or more hours in duration. INTERVENTIONS: Group 1 (n = 29) received desflurane in oxygen (O2) for their surgical procedure. Group 2 (n = 30) received isoflurane in O2 for their surgical procedure. Thiopental sodium 4 mg/kg and fentanyl 3 micrograms/kg provided induction; vecuronium 0.1 mg/kg facilitated intubation. Prior to incision the volatile anesthesia drug was titrated to maintain systolic blood pressure (SBP) within 20% of preinduction (baseline) values. Any time after incision, an SBP increase greater than 20% of baseline was treated with a 30% increase in inspired anesthetic concentration for 3 minutes, or until SBP was within 10% of baseline. Another three 30% increases were allowed at 3 minute intervals to return SBP to 10% of baseline. If four 30% increases did not return SBP to 10% of baseline, additional fentanyl up to 5 micrograms/kg or labetalol in 5 mg increments was given. MEASUREMENTS AND MAIN RESULTS: Measurement of hemodynamics and anesthetic concentration occurred every 2 minutes prior to skin incision and every 5 minutes thereafter. Measurement of hemodynamics and anesthetic concentration occurred every minute during treatment of blood pressure (BP) response to surgical stimulus. Desflurane allowed for more rapid control of BP response to surgical stimulus median 2 minutes (range 1 to 12 minutes) for desflurane versus 6 minutes (range 1 to 12 minutes, p = 0.011). The desflurane group required fewer 30% incremental anesthetic increases than the isoflurane group (1.8 versus 2.5, p = 0.016) to control increased SBP. End tidal/inspired drug concentration ratios were closer to unity in the desflurane patients both before (0.94 versus 0.80) and after (0.86 versus 0.70) changes in drug concentration to treat increased SBP. CONCLUSIONS: Anesthetic depth can be more rapidly titrated with desflurane compared to isoflurane. Alveolar/inspired concentration ratio approaches unity more rapidly with desflurane anesthesia.

Adolescent↗
PubMed1995

Acquired immunodeficiency syndrome and social disease.

The social construction of disease and responses to it has implications not only for how nurses approach caregiving responsibilities but also for how we strategize for and participate in prevention efforts and elaborate priorities for advocacy. Historical review of responses to public health threats, along with critical examination of current social constructions of disease and public health practice, can inform our theory building and offer important insights for educators and clinicians striving to improve the care of people with acquired immunodeficiency syndrome (AIDS). Understanding what underlies responses is key to effecting changes. Although unique, AIDS has commonalities with other diseases and public health threats, past and present. Thus lessons learned from the past may be applicable to the current situation.

Acquired Immunodeficiency Syndrome↗