Search PubMed⌕ Search

Biomedical subjects

T J Gal

Publications and source records attributed to T J Gal.

At least 37 records · Page 2Linked to original sources
PubMed1986

Prolonged blockade of opioid effect with oral nalmefene.

In a placebo-controlled, double-blind study we evaluated the ability of a single 50 mg oral dose of nalmefene to block the effects of intravenous opioid challenge (2 micrograms/kg fentanyl). Fentanyl-induced respiratory depression (CO2 responsiveness), analgesia (tourniquet ischemia), and subjective effects were totally blocked for 48 hours and showed only minimal breakthrough 72 hours after nalmefene. Plasma concentration-time data for nalmefene indicate good oral bioavailability and a prolonged terminal elimination phase (mean t1/2 11.1 hours). These findings suggest that nalmefene could provide prolonged effectiveness in limiting emergence of opioid effects during addiction therapy.

Administration, Oral↗
PubMed1986

Prolonged antagonism of opioid action with intravenous nalmefene in man.

To identify the opioid antagonist activity of nalmefene and to determine its duration in man, six healthy male subjects were pretreated on separate days with a saline placebo, 0.5 mg, 1 mg, or 2 mg nalmefene intravenously in a randomized double-blind fashion. Opioid challenges with fentanyl, 2 micrograms/kg, then were administered 1, 2, 4, 6, and 8 h afterward. Respiratory depression was monitored by ventilatory and occlusion pressure responses during CO2 rebreathing, while analgesia to experimental pain was identified with the submaximal effort tourniquet ischemia test. One hour following placebo pretreatment, the initial fentanyl dose produced marked respiratory depression. Minute ventilation and occlusion pressure at a PCO2 60 mmHg during rebreathing (VE60 and P(0.1)60) were reduced to 29 and 41% of control, respectively. The slopes of the ventilatory and occlusion pressure responses also decreased significantly to 51 and 55% of control. Respiratory effects were similar with all subsequent fentanyl doses. Pretreatment with 2 mg nalmefene completely prevented the subjective and respiratory effects of fentanyl for the entire 8 h of the experiment. Nalmefene, 1 mg, significantly blunted the fentanyl effects for the same period, but VE60 values at 6 and 8 h were depressed significantly (P less than 0.05) to 66 and 61% of control. The antagonist effects of the lowest nalmefene dose, 0.5 mg, persisted for about 4 h, at which time VE60 was 64% of control. Fentanyl administration produced consistent increases in pain tolerance (44-55% above control) throughout the experiment. Nalmefene pretreatment abolished this analgesic response in a dose-related time course that mirrored the respiratory effects almost exactly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Brain-stem auditory-evoked potentials during lidocaine infusion in humans.

Auditory brain-stem responses (ABR) were recorded in six healthy male volunteers during intravenous infusion of lidocaine that achieved systemic blood levels similar to those seen with conduction anesthesia and antiarrhythmic therapy. Following an initial loading dose of lidocaine (1 mg/kg), subjects noted prominent tinnitus, perioral numbness, and drowsiness. All of these symptoms except drowsiness abated during continued infusion as blood concentrations reached equilibrium. All subjects noted that the click stimuli used to elicit ABR varied markedly in intensity and character throughout the lidocaine infusion. Although waves I and III were unaffected by lidocaine, wave V exhibited significant decreases in amplitude and increases in latency. Therefore, the more central components of the auditory system seem to be the prominent site of lidocaine's central nervous system effects.

Acoustic Stimulation↗
PubMed1984

Ventilatory and analgesic effects of dezocine in humans.

The respiratory depressant and analgesic effects of intravenous dezocine were evaluated in six healthy volunteers. Single 0.15 mg/kg doses were compared with identical amounts of morphine, and the two drugs were given in combination. Five successive 0.15 mg/kg doses of dezocine also were given to identify dose-effect relationships. Respiratory center sensitivity was monitored by carbon dioxide (CO2) rebreathing and mouth occlusion pressure (P0.1) measurement, while analgesia to experimental pain was tested with submaximal tourniquet ischemia. Single 0.15 mg/kg doses of dezocine produced significantly more tolerance to experimental pain and greater respiratory depression than a comparable dose of morphine in the first hour, but effects of both drugs were similar thereafter. Multiple doses of dezocine progressively increased pain tolerance from 46 +/- 14% above control with the first dose to 70 +/- 18% above control with the second dose (cumulative total 0.30 mg/kg). Additional dezocine doses did not result in significantly more analgesia. Depression of CO2 sensitivity followed a similar pattern. Morphine 0.15 mg/kg, when given to subjects who had received a prior dose of dezocine, produced no additional effect beyond that observed with dezocine. With the reverse sequence, dezocine increased the respiratory depression of morphine but also produced a dramatic increment in analgesia, which suggested an additive action. Dezocine is therefore an effective analgesic with morphine-like effects. In human subjects it appears to be a slightly more potent analgesic than morphine in identical clinical doses (0.15 mg/kg). Dezocine is similar to other agonist-antagonist analgesics in that it exhibits a ceiling effect for respiratory depression that parallels its analgesic activity.

Adult↗
PubMed1984

Glycopyrrolate and atropine inhalation: comparative effects on normal airway function.

Bronchodilation was produced in normal subjects by inhalation of high doses of a quaternary parasympatholytic agent (glycopyrrolate), and responses were compared with those of atropine and a placebo. Both drugs induced significant increases in specific airway conductance (SGaw) and forced expiratory flows, but the effects of glycopyrrolate were sustained significantly longer (greater than 6 h). Whereas atropine produced an increased heart rate (26%) and severe dry mouth in all subjects, these symptoms were absent with glycopyrrolate and placebo. Therefore, glycopyrrolate produces significant bronchodilation of long duration but free of the side effects of muscarinic blockade that characterize atropine inhalation.

Adult↗
PubMed1984

Effect of inhaled glycopyrrolate and atropine in asthma. Precipitated by exercise and cold air inhalation.

We compared the effects of inhaled glycopyrrolate (G), 1.3 mg, and atropine (A), 2.6 mg, and placebo on FEV1 and specific conductance (sGaw) before and after exercise in six men with exercise-induced asthma. Subjects exercised with cold air (-2 degrees C) 30 and 120 minutes after each aerosol treatment. Spirometry was performed and sGaw determined before aerosol treatment (baseline) and before and after exercise. Decreased airway tone was noted before exercising with A and G but not with placebo. The decreases in FEV1 and sGaw resulting from exercise were not significantly different among the three treatment groups at either exercise session. Postexercise FEV1 and sGaw were significantly higher after A and G compared to P. Dry mouth, flushing, and resting tachycardia were prominent with group A. Symptoms in G did not differ from those in P. This study suggests that A and G do not prevent bronchoconstriction induced by exercise and cold air but improve postexercise pulmonary function by achieving preexercise bronchodilation. Systemic side effects were minimal with G compared to A.

Adolescent↗
PubMed1984

Cerebral and cardiopulmonary responses to high-frequency jet ventilation and conventional mechanical ventilation in a model of brain and lung injury.

The cardiopulmonary and intracranial effects of high-frequency jet ventilation (HFJV) were evaluated in four groups of 10 mongrel dogs and compared to conventional mechanical ventilation with and without positive and expiratory pressure (PEEP). Each group of animals was studied with various combinations of normal and abnormal brain and lung function. Experimental brain injury (abnormal cerebral elastance) was produced by infusion of saline into the subarachnoid space to increase intracranial pressure (ICP), while lung injury resulted from intratracheal instillation of 0.1N HCl. Animals responded similarly to HFJV and conventional ventilation except for those with abnormal lungs, in whom peak airway pressures were significantly lower with HFJV (P less than 0.05). The application of PEEP (10 and 20 cm H2O) produced significant increases in mean airway pressure compared to HFJV (P less than 0.05). Animals with abnormal lungs demonstrated significantly improved mean PaO2 (194 vs 104 mm Hg) and shunt fraction (0.20 vs 0.45) with 20 cm H2O PEEP compared to HFJV. In all dogs subjected to 20 cm H2O PEEP, cardiac index and mean arterial pressure were decreased significantly (P less than 0.05) below values with HFJV. ICP responses did not vary significantly with the different modes of ventilation and were not influenced by the status of lung or brain function. However, significant reductions in cerebral perfusion pressure were noted with 20 cm H2O PEEP compared to HFJV. We conclude that unless high levels of PEEP (15-20 cm H2O) are required for adequate oxygenation, the cardiovascular and cerebral effects of HFJV do not differ significantly from those of conventional mechanical ventilation.

Airway Resistance↗
PubMed1982

Analgesic and respiratory depressant activity of nalbuphine: a comparison with morphine.

To compare the respiratory depressant and analgesic effects of nalbuphine and morphine, six healthy male subjects were given the drugs as single 0.15-mg/kg doses, and as four successive doses of 0.15 mg/kg. Respiratory depression was monitored by ventilatory and mouth occlusion pressure responses during CO2 rebreathing, while analgesia to experimental pain was tested with the submaximal effort tourniquet ischemia test. When given as single 0.15 mg/kg doses, both drugs significantly increases the threshold and tolerance for experimental pain. The analgesic effect was similar for both drugs at this dosage, as was depression of the ventilatory and occlusion pressure responses to CO2. Morphine administered in multiple doses progressively increased pain tolerance from 30 +/- 13% above control with the first dose of 0.15 mg/kg to 107 +/- 13% above control after the fourth dose (cumulative total 0.60 mg/kg). Nalbuphine produced a 40 +/- 12% increase in pain tolerance with an initial dose of 0.15 mg/kg, but additional increments of nalbuphine did not result in significantly greater analgesia. The increasing morphine dosage was associated with progressive rightward displacements and ultimately decreases in the slope of the CO2 response curves. Nalbuphine produced an initial rightward displacement of the CO2 response curves similar to morphine, but continued administration of the drug did not result in further displacement or changes in slope. These findings demonstrate that nalbuphine, in contrast to morphine, exhibits a ceiling effect for respiratory depression which is paralleled by its limited analgesic effect on experimental pain.

Adult↗
PubMed1982

Respiratory mechanics in supine subjects during progressive partial curarization.

Respiratory mechanics were studied in six supine conscious volunteers during progressive muscle weakness produced by infusion of d-tubocurarine. Partial curarization was carried out to the point of abolishing head lift ability and handgrip strength. At all levels of partial paralysis, expiratory muscle strength was significantly more impaired than inspiratory strength. Despite this, subjects maintained relatively normal maximal expiratory flow rates, whereas inspiratory flows decreased significantly. The diminished inspiratory flows are not fully explained by decreased driving pressures during force inspiration, since inspiratory resistance increased significantly with the decreased flow. Inspiratory flow patterns suggest a variable extrathoracic obstruction most likely due to the absence of normal airway abductor activity during inspiration. Maximal respiratory muscle weakness decreased forced vital capacity by 29% and total lung capacity by 15%. The decreased level of lung inflation did not alter lung elastic recoil. Functional residual capacity was unchanged, but inspiratory capacity decreased by 25% and residual volume increased by 38%. These changes are in accord with predictions based on the decreased muscle strength and normal respiratory system recoil.

Adult↗
PubMed1982

Stapedius reflex in curarized subjects: an index of neuromuscular weakness.

To examine the validity of the acoustical stapedial reflex (AR) as an index of neuromuscular weakness, the AR was measured along with other indices of muscle strength during administration of d-tubocurarine (dTc) to six healthy subjects. AR decreased immediately after each dTc dose and preceded changes in handgrip strength and respiratory muscle strength, but the peak effects of each dose similarly affected AR and other muscle strength. The findings with electrocutaneous stimulation and effects on growth function of the AR indicate that dTc affects primarily stapedius muscle contraction, the efferent portion of the reflex arc, and does not affect afferent or central portions of the reflex. We therefore conclude that the AR is a valid index of the integrity of neuromuscular transmission which promptly reflects early phase weakness. Unlike other measures of muscle strength, AR testing does not depend on subject cooperation, and involves no discomfort. The test therefore provides a useful means of assessing neuromuscular weakness.

Adult↗
PubMed1981

Effect of head flexion on airway resistance measured in a body plethysmograph.

We measured the effects of partial (21 degrees) and full (43 degrees) flexion of the head on airway resistance (Raw) and specific conductance (SGaw) in eight normal subjects and two patients with mild obstructive lung disease. With partial head flexion, mean Raw increased by 32% and SGaw decreased by 26% compared to control. With full head flexion Raw increase 75% and SGaw decreased 42%. All values are significantly different from control (p less than 0.005). We suggest that subjects in a body plethysmograph be instructed to sit as erect as mouthpiece positioning will allow.

Adult↗
PubMed1981

Relationship between respiratory muscle strength and vital capacity during partial curarization in awake subjects.

To determine the relationship between respiratory muscle strength and changes in normal vital capacity (VC), graded levels of muscle weakness were produced in six healthy supine male subjects by four successive doses of d-tubocurarine (0.05 mg/kg each). The maximal effect of d-tubocurarine abolished hand-grip strength and ability to sustain head lift for 5 s, but VC was decreased to only 66 +/- 3 per cent of control. At each level of weakness decreases in VC were significantly less than were decreases in respiratory muscle strength (RMS) monitored by maximum static inspiratory and expiratory pressures. The first dose decreased RMS to 86 +/- 3 per cent of control, but VC was unchanged. Following the second dose,, VC (97 +/- 4 per cent). The VC after the third dose was still 85 +/- 3 per cent of control, while RMS had decreased to 58 +- 2 per cent. Following the final dose of d-tubocurarine (cumulative total 0.20 mg/kg), RMS was 39 +/- 2 per cent of control, compared with VC, 66 +/- 3 per cent of control. The relationship between VC and RMS was curvilinear and conformed to predictions based on the static mechanical characteristics of the normal respiratory system. These findings demonstrate that while VC is relatively spared during partial curarization, this sparing of VC does not indicate a similar extent of preserved RMS. Rather, it reflects the relative ease with which weakened respiratory muscles are able to drive the normal respiratory system in the supine subject. The same weakened muscles may be unable to generate sufficient force to handle mechanical challenges such as coughing and vomiting.

Adult↗
PubMed1981

Cough dynamics during progressive expiratory muscle weakness in healthy curarized subjects.

The dynamics of voluntary cough were studied in healthy supine subjects during four successive infusions of d-tubocurarine (dTc) (0.05 mg/kg) to assess the effects of progressive expiratory muscle weakness on cough performance. Curarization produced a progressive decline in maximal static expiratory muscle strength (PEmax) measured at the mouth and in pleural pressures (Ppl) generated during coughing. Expiratory flow rates during coughing did not decrease except during the initial cough from total lung capacity with the last dTc dose (18% below control). This was associated with a decrease in end-inspiratory volume prior to coughing and with a marked decrease in Ppl to 30% of control. Although the decrease in flow rates was minimal compared with Ppl, flow patterns suggest that dynamic airway compression was reduced during these coughs. We conclude that the principal effect of the expiratory muscle weakness in curarized subjects is to reduce the cough-induced dynamic compression and linear velocity of airflow though the major intrathoracic airways.

Adult↗
PubMed1981

Atropine and glycopyrrolate effects on lung mechanics in normal man.

To assess the comparative bronchomotor effects of large systemic doses of glycopyrrolate and atropine intravenous glycopyrrolate (10 micrograms/kg), atropine (20 micrograms/kg), or a placebo was administered to six healthy male volunteers in double-blind fashion. Both drugs produced bronchodilation reflected by significant decreases in airway resistance and increases in specific airway conductance (sGAW) compared to placebo. Glycopyrrolate increased sGAW to a maximal level of 100% +/- 7% above control; bronchodilation persisted at this level for more than 4 hours after drug administration. Atropine increased sGAW to a maximum of 88% +/- 5% above control 30 minutes after administration, but sGAW returned to control levels between 3 and 4 hours after the drug was given. Both drugs increased maximum expiratory flow rates over the same time course as sGAW, but the percent increases in flow were significantly less than changes in sGAW. Lung elastic recoil was decreased by both drugs over the full range of lung volume. The 32% maximum increase in heart rate after glycopyrrolate was significantly less (p< 0.01) than the 60% increase after atropine. It was concluded that vagal blockade with glycopyrrolate dilates large and small airways to the same extent as atropine, but that the effect is more sustained and associated with less cardiac vagal blockade. Lower doses of glycopyrrolate were also studied and the findings showed that maximal bronchodilation is achieved with lower doses (3.2 micrograms/kg), which are commonly used in routine premedication.

Adult↗
PubMed1980

Effects of endotracheal intubation on normal cough performance.

To assess the effects of endotracheal intubation on normal cough function, the tracheas of eight healthy volunteers were intubated with a standard 8.0-mm-I.D. tube. Measurements were made of expiratory flow, transpulmonary pressure, and expired volume during a cycle of three successive bursts of maximum voluntary coughing initiated after inspiration to total lung capacity. Results following intubation were compared with findings with subjects breathing through a 25-mm-I.D. mouthpiece (control). Maximum cough pressures (Pmax) following tracheal intubation were similar to control values, but with the tube in place, airflow began well before Pmax was reached and did not cease fully between cough bursts. Flows at Pmax declined with each successive burst of coughing during both experimental conditions, but with tracheal intubation, the flows were significantly lower than control. Resistance to flow at Pmax increased with each successive cough and increased significantly above control during the third burst of coughing while the subjects' tracheas were intubated. The total volume of the three control coughs was 76 +/- 3 per cent of vital capacity. This was similar following intubation, although cough duration was significantly longer. These findings indicate that tracheal intubation does not impair ability to develop normal cough pressures despite preventing glottic closure. The normal timing of flow and pressure is disrupted such that flow occurs early--as in a forced expiratory maneuver, and the flow is not fully interrupted during the cough sequence. Flows are submaximal as a result of the resistance of the tube and continue to decline as the lung volume decreases and airways are compressed. Because the tube is noncollapsible, high flow rates may be necessary to achieve the linear velocities requireed for normal airway cleansing through the tube. Such flows may be achieved only during the initial cough after full inspiration.

Adult↗
PubMed1980

Diaphragmatic function in healthy subjects during partial curarization.

Diaphragmatic function estimated by transdiaphragmatic pressure (Pdi) was studied in eight normal subjects during progressive partial paralysis with d-tubocurarine (dTc). Dynamic Pdi was measured during quiet tidal breathing, maximum deep inspiration, and 12-s maximum voluntary ventilation (MVV). Maximum static transdiaphragmatic pressure (Pdimax) was also measured during maximum static inspiratory efforts at four lung volumes. The maximum effect of dTc at a cumulative dose of 0.2 mg/kg abolished head-lift and handgrip ability. Pdimax at functional residual capacity was decreased to 42% of its control value indicating significant diaphragmatic weakness at this level of curarization. The weakness had no inpact on quiet breathing and a moderate effect on maximum inspiration. In either case Pdi represented an increasing fraction of Pdimax. MVV fell significantly before the Pdi during the maneuver decreased. This decreased MVV in curarized subjects reflects upper airway obstruction caused by pharyngeal muscle weakness and the diminished contribution of the other respiratory muscles that are important at high levels of ventilatory effort but more sensitive to effects of dTc.

Adult↗