High frequency ventilation.
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High-Frequency Jet Ventilation↗
Biomedical subjects
R B Smith
Publications and source records attributed to R B Smith.
Evaluation of the interaction of lithium and alprazolam.
A potential pharmacokinetic interaction between lithium and alprazolam was studied in 10 normal subjects. Pharmacokinetic parameters were determined from the following regimens: single-dose alprazolam, multiple-dose lithium, and multiple-dose alprazolam with lithium. Steady-state alprazolam clearance during multiple dosing with lithium was not different from that with the single dose of alprazolam. Lithium renal clearance decreased when it was coadministered with alprazolam (31.2 vs. 22.4 ml/minute, p less than 0.05). There was a small but significant increase in the steady-state area under the curve for lithium in the presence of alprazolam (10.3 vs. 11.1 mEq/hour/liter). The small increase in the serum lithium concentrations and decrease in lithium renal clearance was probably the result of lower urine flow rates (1.46 vs. 0.98 ml/minute, p less than 0.05) with the combination of the drugs. This is supported by a weak but significant linear relationship between urine flow rates and lithium renal clearance (N = 57, r = 0.353, p = 0.007). The percent of daily lithium dose recovered at steady-state from the 24-hour urine collection decreased significantly from 93.6% to 78.2% in the presence of alprazolam. This suggests that alprazolam may decrease lithium absorption. The results of this study do not support a definitive interaction of lithium and alprazolam and there is little clinical significance to the small rise in serum lithium concentrations.
Adult↗
Work-place stretching programs reduce costly accidents, injuries.
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Accidents, Occupational↗
Always in the hot seat.
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Equipment Design↗
Postcatheterization vascular complications associated with percutaneous transluminal coronary angioplasty.
The threat of a vascular complication exists in association with any percutaneous arterial catheterization, but is greater in the more complex interventional techniques. During a 3 1/2-year period from January 1985 through June 1988, 4988 percutaneous transluminal coronary angioplasty procedures were performed at Emory University Hospital. All patients were given heparin during the cardiac intervention, and all had a catheter introducer left in place for several hours after completion of the procedure. Fifty-five iatrogenic vascular complications developed in 52 patients (1%), resulting in 54 corrective operations. Pseudoaneurysm, the most frequent complication, was seen in 35 patients (64%). This was followed by arteriovenous fistula in eight (15%), uncontrolled hemorrhage in six (11%), arterial thrombosis in three (6%), peripheral embolization in two (4%), and bowel ischemia in one patient. The outcome of surgical therapy in the entire group was quite acceptable with no operative mortality, no extremity amputation, and a 7.4% complication rate. Variables that correlated with an increased risk of peripheral vascular problems after percutaneous transluminal coronary angioplasty included advanced age, female gender, thrombolytic therapy, and postprocedural anticoagulation. Variables that did not appear to correlate were hypertension, diabetes, prior percutaneous transluminal coronary angioplasty, antiplatelet therapy, or the size of the guiding catheter used.
Aged↗
Pharmacokinetics and pharmacodynamics of alprazolam following single and multiple oral doses of a sustained-release formulation.
The pharmacokinetics and pharmacodynamics of alprazolam after IV and oral sustained-release (SR) tablet administration were evaluated in 42 healthy, normal, male volunteers. All 42 subjects received a single 1-mg intravenous (IV) alprazolam dose. After a 1-week washout period, the subjects received one of three SR treatments as a single dose: one 1-mg SR tablet, three 1-mg SR tablets, or six 1-mg SR tablets. Beginning 2 days after single-dose SR treatment, each subject received the above SR doses for 3 days. The daily dose for the multiple-dose study was the same as the subject received in the single-dose study. Serial blood samples were collected after each treatment (single-dose IV, single-dose SR, and after the last SR multiple dose), and plasma samples were analyzed by high performance liquid chromatography. Sedation was assessed by a blinded observer at each blood sampling time. Mean pharmacokinetic parameters for IV administration were consistent with previous results. Pharmacokinetic parameters for the SR doses were consistent with linear kinetics over the dosage range studied. The mean absolute bioavailabilities of the SR tablets were greater than 0.84 after single SR doses. Maximal sedation was related to dose after single-dose SR administration. During multiple dosing, chronic tolerance was observed. Maximal sedation scores after 3 days of alprazolam SR administration were independent of the dose administered and were lower after multiple-dose administration than scores observed after single oral SR doses, although plasma alprazolam concentrations were at least 1.5 times higher with multiple dosing. Sedation data indicate that oral SR doses were well tolerated in multiple dosing.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Multiple-dose pharmacokinetics and pharmacodynamics of adinazolam in elderly subjects.
The pharmacokinetics and pharmacodynamics of adinazolam (AD) were evaluated in 21 elderly subjects (mean age, 69 +/- 4 years) at four dose levels during a placebo-controlled, double-blind, dose escalation regimen in which the oral dose was varied from 10 to 60 mg daily, in divided doses. Fifteen subjects received adinazolam mesylate; six received placebo. Plasma samples collected during a single dosing interval in each dosing period (3 days) were assayed for adinazolam and monodesmethyl adinazolam (NDMAD) by high-performance liquid chromatography (HPLC). Urine samples were collected during a single interval during the 20- and 40-mg daily dose periods and assayed for NDMAD by HPLC. Pharmacologic effects of adinazolam were assessed using psychomotor performance tests and sedation ratings. Adinazolam pharmacokinetics were linear over the dosage range studied. Daily dose had no significant effect on dose-normalized AUC and Cmax for AD. Dose-normalized NDMAD AUC values as well as beta values were not significantly affected by the daily dose of adinazolam. The ratio NDMAD/AD was not substantially affected by the dose. Renal clearance of NDMAD for the 20- and 40-mg daily doses were 5.6 +/- 2.1 and 5.5 +/- 2.2 liters/hr, respectively, and did not correlate with creatinine clearance. Adinazolam and NDMAD did not substantially accumulate in elderly subjects, even upon multiple dosing at 8-hr intervals. The dosing regimens in this experiment appeared to be well tolerated in the elderly, as performance tests and sedation scores indicated no substantial dose-related effects of adinazolam on psychomotor performance.
Aged↗
An evaluation of population pharmacokinetics in therapeutic trials. Part III. Prospective data collection versus retrospective data assembly.
The ability to estimate population pharmacokinetic parameters of alprazolam from fragmentary clinical data collected during clinical efficacy trials was evaluated in this series of studies. In the first study modifications to the protocol and case report forms were employed to allow for the prospective collection of accurate dosing and blood sampling time data. In the second study only total daily dose and measured drug concentration data were recorded. Dosage and blood sampling time data were assembled retrospectively by assuming strict adherence to protocol guidelines. Comparisons of the results of these analyses demonstrate the marked impact of prospective data collection efforts on data quality and the ability to determine subsequent pharmacokinetic parameters. Analysis of the prospectively collected data yielded pharmacokinetic estimates for alprazolam that were nearly identical to previously reported values obtained according to traditional methods, whereas the analysis of retrospectively collected data yielded biased estimates of the mean pharmacokinetic parameters and markedly upward biased estimates of both interindividual and residual variability. These analyses demonstrate the ability to estimate population pharmacokinetic parameters from data collected during clinical efficacy trials, provided that critical issues pertaining to the design and use of data collection forms to enhance data quality and the education of patients and staff are satisfactorily addressed.
Adult↗
Maternal, cord, and neonatal carnitine correlations and lipid profiles of various birthweight infants.
The carnitine, acylcarnitine, and triglyceride concentrations were determined in the average for gestational age neonates of various birthweights and gestational ages and their corresponding maternal and umbilical cord plasma. Forty-two infants were divided into one of four groups based on birthweight: Group 1, less than 1000 gm; group II, 1001 to 1510 gm; group III, 1511 to 2500 gm; and group IV were term infants who served as the reference group. Results indicated that there was an overall decrease of total carnitine and nonesterified carnitine with advancing gestational age (r = -0.4418, p less than 0.01). Furthermore, there were three distinct phases of plasma carnitine concentrations from 24 weeks to term. The plasma carnitine profile of the neonates less than 1500 gm was strongly correlated (r = 0.73) to their maternal plasma carnitine profile and that of term neonate to their umbilical cord plasma. Acylcarnitine and triglycerides were not significantly correlated.
Birth Weight↗
Effect of the bile-acid sequestrant colestipol on postprandial serum bile-acid concentration: evaluation by bioluminescent enzymic analysis.
Chronic ingestion of bile-acid sequestrants has been shown to decrease the serum cholesterol concentration and coronary events in hypercholesterolaemic patients. To develop improved sequestrants, a rapid, convenient method for testing the bile-acid binding efficacy of sequestrants is needed. Serum bile-acid concentrations could be used to detect bile-acid binding by an administered sequestrant, since the serum bile-acid concentration is determined largely by the rate of intestinal absorption in healthy individuals. To test this, serum bile-acid concentrations were measured at frequent intervals over 24 h in five otherwise healthy hypercholesterolaemic subjects during the ingestion of three standard meals, with or without the addition of 5 g colestipol granules administered 30 min before each meal. Total serum bile-acid concentration was measured with a previously reported bioluminescent enzymic assay, that uses a 3 alpha-hydroxysteroid dehydrogenase, an oxido-reductase, and a bacterial luciferase co-immobilized on to Sepharose beads. Bile acids in 1 ml of serum were isolated by solid-phase extraction chromatography with reversed-phase C18 cartridges. Colestipol lowered the postprandial elevation of serum bile acids by one half, with a subsequent decrease in the cumulative area under the curve. The data suggest that measurement of serum bile-acid concentrations by bioluminescence is a rapid, simple way to document the efficacy of bile-acid sequestrants.
Adolescent↗
Relationship of triazolam clearance to alpha-1 acid glycoprotein concentrations.
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Humans↗
Low-compliance, volume-controlled, high-frequency positive-pressure ventilation versus conventional ventilation during coronary artery bypass grafting.
Low-compliance, volume-controlled, high-frequency positive-pressure ventilation (HFPPV) was compared to conventional intermittent positive-pressure ventilation (IPPV) immediately before and after surgery in a series of ten patients who underwent coronary artery bypass grafting (CABG). Direct and indirect hemodynamic and respiratory variables were recorded and calculated. All patients were adequately ventilated with either HFPPV or IPPV. No significant differences in hemodynamic stability were noted either before or after cardiopulmonary bypass (CPB). Airway pressures were lowered significantly by HFPPV as compared to IPPV. This may be useful in cases in which increased airway pressure might be harmful due to decreased venous return and cardiac output (CO).
Aged↗
Tolerance to alprazolam after intravenous bolus and continuous infusion: psychomotor and EEG effects.
A study was undertaken to compare the time course of changes in psychomotor performance and spectral edge (SE) of the EEG and to relate these changes to alprazolam concentrations in a pharmacokinetic/pharmacodynamic tolerance model. Digit symbol substitution (DSS) tests were administered and EEG data were obtained for SE calculation in a four-way crossover study in four normal men. Each treatment consisted of a 2-minute bolus injection followed by an 8-hour infusion. Treatment A, placebo, consisted of a 50% propylene glycol injection followed by a saline infusion. Active drug treatments were: B, 0.5 mg alprazolam plus saline infusion; C, 2.0 mg alprazolam plus saline; and D, 1.0 mg plus 72 micrograms alprazolam/hr for a total dose of 1.576 mg in 8 hours. For both DSS and SE data, three distinct effect-concentration curves result from the three alprazolam treatments, with successive shifts to the right as dose increases. A tolerance rate constant (kt) of 0.15 hr-1 was calculated from the DSS vs. time data during the 8 hour alprazolam infusion. The Hill equation was altered by using kt in an exponential modification of EC50. The resulting tolerance model describes both DSS and SE vs. concentration data from the rapid-injection and continuous-infusion treatments.
Adult↗
Reducing the risks of laryngoscopy in anaesthetised infants.
We have evaluated the use of oxygen insufflation during laryngoscopy with an Oxyscope laryngoscope blade compared to conventional laryngoscopy for maintenance of transcutaneous PO2 during intubation of anaesthetised, spontaneously breathing infants. Twenty healthy children aged between 1 and 24 months were anaesthetised with halothane in oxygen. Laryngoscopy and intubation were performed in a double-blind fashion using a Miller No. 1 Oxyscope blade either with or without oxygen insufflation. Transcutaneous oxygen tension, arterial pressure and heart rate were measured before and after laryngoscopy, and duration of laryngoscopy was recorded. Transcutaneous oxygen tension decreased by 7.1% (SD 6.1%) when oxygen insufflation was used, compared to 33.0% (SD 15.1%) without oxygen insufflation (p less than 0.0001). There were no significant differences in mean duration of laryngoscopy or patient age. We conclude that oxygen insufflation during laryngoscopy and intubation of spontaneously breathing, anaesthetised infants effectively minimises the decrease in transcutaneous oxygen tension from pre-laryngoscopy levels, and makes instrumentation of the airway safer.
Anesthesia, Inhalation↗
Continuous-flow apneic ventilation with small endobronchial catheters.
This study compares gas exchange and hemodynamic parameters during bronchial insufflation with two different internal diameter (ID) catheters (2.5 and 1.4 mm) at a constant mean gas exit velocity. Anesthetized, paralyzed dogs were instrumented to monitor arterial, central venous, and airway pressures, blood gases, temperature, ECG, and ventilated using continuous flow apneic ventilation (CFAV) via 2.5-mm or 1.4-mm ID bronchial insufflation catheters positioned 1.25 bronchial diameter units (BDU) beyond the carina. Initially, flow was adjusted to provide adequate oxygenation and ventilation through the 2.5-mm ID catheters. After a 30-min stabilization, physiological parameters were recorded and the mean gas exit velocity was calculated. The 2.5-mm ID insufflation catheters were then replaced by 1.4-mm ID catheters and the bronchial insufflation flow adjusted so as to produce the same mean gas exit velocity as for the 2.5-mm ID catheters. After a 30-min stabilization period, physiological parameters were again recorded. No significant differences were noted in arterial, central venous, or airway pressures, temperature, heart rate, pH, PaCO2, and PaO2 between the 2.5-mm and 1.4-mm ID bronchial insufflation catheters. However, significantly less bronchial insufflation flow (69.7%) was required to maintain oxygenation and ventilation for the 1.4-mm ID bronchial insufflation catheters.
Animals↗
Comparative efficacy and tolerability of two ointment and suppository preparations ('Uniroid' and 'Proctosedyl') in the treatment of second degree haemorrhoids in general practice.
A multi-centre general practice, open study was carried out in 89 patients with second degree haemorrhoids to compare the efficacy and tolerability of two antibiotic-corticosteroid combinations ('Uniroid' and 'Proctosedyl') in ointment and suppository formulations. Patients were allocated at random into 4 groups and received treatment with one of the trial preparations for 1, 2 or 3 weeks, as required, with weekly assessments of response. There were no significant differences between the various groups at the start of treatment. Significant improvement occurred in all groups during treatment. Both suppository and ointment formulations were broadly comparable and control of symptoms was achieved from Week 2 onwards, building up to levels in excess of 90% after 3 weeks of therapy. With regard to the symptoms of pain and itching, suppositories gave marginally greater relief in the early stages of treatment, while both ointment and suppositories were associated with similar reduction in bleeding from haemorrhoids. Whereas both suppository formulations were about equal in reducing anal discharge, 'Uniroid' ointment was clinically superior to 'Proctosedyl' ointment in controlling this symptom over the 3-week trial period. No unwanted effects were experienced attributable to treatment. No statistically significant differences between the two ointment and the two suppository formulations were identified in this study and all four preparations were found to be efficacious in the majority of patients studied.
Adult↗