The temporal relationship between the secretion of luteinizing hormone and testosterone in man.

It has been suggested recently that testosterone secretion by the human testis may be controlled by factors other than luteinizing hormone (LH). In order to re-examine this hypothesis, plasma LH and testosterone concentrations were determined throughout the day in eight studies. A new method of data analysis revealed that the levels of the two hormones were closely related, but that the testicular response to LH was sluggish. These results explain some inconsistencies in the literature. It was demonstrated that average values for LH varied throughout the day, with a morning maximum and an evening minimum. It was also shown that injections of LH releasing hormone in man resulted in an increase in plasma testosterone above control levels. These results are consistent with the concept that LH controls the major changes in testosterone secretion in men. They do not exclude, however, the possible existence of other factors which might affect the peripheral concentration of testosterone, such as changes in testicular blood flow.

Alcohol induced discoordination is not reversed by naloxone.

It has previously been reported that prior administration of naloxone may prevent the decrement in performance produced by alcohol. To be clinical value, however, naloxone must be shown to reverse rather than prevent this decrement. This study examined the effect of naloxone given after consumption of alcohol. A double blind balanced crossover protocol was used to examine the effect of either 1.2 mg or 10 mg naloxone on the sensory-motor impairment produced by blood alcohol concentrations maintained between 75 and 85 mg/100 ml. This alcohol concentration significantly impaired two measures of sensory-motor performance, but there was no evidence that either dose of naloxone could reverse this decrement. We tested our subjects for a chlorpropamide alcohol flush but none gave a positive response. These results indicate that naloxone (1.2 mg or 10 mg) does not reverse the sensory-motor impairment produced by alcohol intoxication in subjects who do not exhibit a chlorpropamide alcohol flush. Nearly all the subjects exhibited somnolence after receiving alcohol and naloxone (1.2 mg or 10 mg) but not after receiving alcohol and saline.

Post-traumatic stress disorder in physically abused adolescents.

OBJECTIVE: In an investigation of the prevalence of post-traumatic stress disorder (PTSD), other Axis I psychiatric disorders, and social and behavioral difficulties, 27 physically abused adolescents were compared with 27 nonabused controls who were recruited through random-digit dialing procedures. METHOD: The Structured Clinical Interview for Diagnosis (PTSD module), Kiddie-Schedule for Affective Disorders and Schizophrenia, and Youth Self-Report were administered to all subjects; mothers were interviewed regarding their adolescent's behavior using the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children and Child Behavior Checklist. RESULTS: The three physically abused adolescents who received a diagnosis of PTSD on the PTSD module of the Structured Clinical Interview for Diagnosis reported their PTSD symptoms were in reaction to extrafamilial sexual assaults and not to physical abuse. In contrast, the abused adolescents showed significantly higher prevalence rates of depression, conduct disorder, internalizing and externalizing behavior problems, and social deficits. CONCLUSIONS: Findings suggest that physically abused adolescents may be more at risk for behavioral and social difficulties than for PTSD.

Minimum fresh gas flow requirements of anaesthetic breathing systems during spontaneous ventilation: a graphical approach.

A general solution is presented to the problem of finding the minimum fresh gas flow requirements, during spontaneous ventilation, of anaesthetic breathing systems in the Mapleson classification. The solution is applicable to any pattern of breathing, dead space volume and tidal volume. The method is graphical and its use and understanding require no mathematical skills. However, if an analytical form of the respiratory waveform is known, the method is easily extended by use of calculus to obtain a precise analytical solution.

Difficult tracheal intubation in obstetrics.

Difficult intubation has been classified into four grades, according to the view obtainable at laryngoscopy. Frequency analysis suggests that, in obstetrics, the main cause of trouble is grade 3, in which the epiglottis can be seen, but not the cords. This group is fairly rare so that a proportion of anaesthetists will not meet the problem in their first few years and may thus be unprepared for it in obstetrics. However the problem can be simulated in routine anaesthesia, so that a drill for managing it can be practised. Laryngoscopy is carried out as usual, then the blade is lowered so that the epiglottis descends and hides the cords. Intubation has to be done blind, using the Macintosh method. This can be helpful as part of the training before starting in the maternity department, supplementing the Aberdeen drill.

Rebreathing during spontaneous and controlled ventilation with T-piece breathing systems: a general solution.

A general solution is presented to the problem of finding the degree of rebreathing generated by T-piece breathing systems. The solution is applicable to any ventilatory waveform, dead space volume and tidal volume and is identical for spontaneous and controlled ventilation for any given ventilatory waveform. The method is graphical and its use and understanding require no mathematical skills. However, if an analytical form of the ventilatory waveform is known, the method is easily extended by use of calculus to obtain a precise analytical solution.

Respiratory depression following diazepam: reversal with high-dose naloxone.

The authors compared the effects of naloxone and saline solution on the respiratory changes following diazepam in a double-blind crossover trial in six subjects. Following baseline measurements of respiration, each subject was given diazepam, 15 mg, intravenously. Sixty and ninety-five minutes later each subject received either two doses of naloxone, 15 mg, intravenously, or two doses of the equivalent volume of saline solution. Forty-five minutes after diazepam administration the slopes of the curves of the ventilatory responses to rebreathing carbon dioxide (VE/PETCO2) were depressed to 53 per cent of control (P < 0.05). Following the two doses of naloxone, the slopes of VE/PETCO2 recovered, until, 120 minutes after the second dose of naloxone, slopes had returned to control values. After saline solution, however, slopes remained depressed at 68 per cent of control (P < 0.05). A similar recovery following naloxone was observed in the PETCO2 intercept of the VE/PETCO2 response curve and in the slope of the mouth-occlusion-pressure response curve to rebreathing carbon dioxide. End-tidal carbon dioxide during quiet breathing and during inspiratory resistive-loaded breathing (80 cm H2O/l/s) showed small increases after diazepam, which were not significantly reduced by naloxone. The results of this study show that diazepam produces respiratory depression, and that this may be relieved by large doses of naloxone.

Effect of the antitussive glaucine on bronchomotor tone in man.

In view of the observation that the antitussive agent glaucine prevents histamine-induced bronchoconstriction in guinea pigs we investigated this agent for a possible peripheral action in man, using a new method for measuring changes in bronchomotor tone. The forced airflow oscillation method was used to determine respiratory resistance (Rrs) over a range of lung volumes (VL) in seven healthy supine subjects. Computer analysis of the hyperbolic relationship between Rrs and VL was used to determine the asymptotic resistance and yield estimates of lower airways conductance (Glaw). Specific lower airways conductance (sGlaw) was expressed as the slope of the linear plot of Glaw against VL and is a sensitive index of bronchomotor tone. After baseline measurements of sGlaw subjects received placebo or 60 mg glaucine orally according to a double-blind crossover protocol. Histamine, 500 micrograms, was inhaled 45 minutes later. Measurements of sGlaw were repeated every 10 minutes for two hours. Although there was a trend towards bronchodilatation after glaucine administration (sGlaw = 130% of baseline) there was no significant difference from the effect of placebo (sGlaw = 89% of baseline). After inhalation of histamine sGlaw fell to 26% of baseline after both glaucine and placebo (p less than 0.01). In a further study three subjects received glaucine and placebo according to an identical protocol except that the histamine was omitted. Again the increase in sGlaw failed to achieve significance. Glaucine does not affect the bronchoconstrictor response to histamine in man and there is no convincing evidence of an effect on resting bronchomotor tone.

A comparison of the respiratory effects of meptazinol, pentazocine and morphine.

The respiratory effects of a new strong analgesic, meptazinol, were compared with a placebo and with equianalgesic doses of morphine and pentazocine in a double-blind crossover trial in seven healthy volunteers. No significant change in the ventilatory response to rebreathing carbon dioxide was observed after meptazinol 100 mg/70 kg or placebo. However, both morphine 10 mg/70 kg and pentazocine 60 mg/70 kg depresesd the slope of the ventilatory response (-30.0% and -31.6% respectively, P less than 0.02, averaged over the first 3.5-h period). End-tidal carbon dioxide tension (PE'CO2) while breathing room air increased significantly following all three drugs. However, the increase in PE'CO2 after meptazinol (0.22 kPa averaged over 3.5 h) was significantly less than that following morphine (0.40 kPa, P less than 0.05) and pentazocine (0.59 kPa, P less than 0.01). While breathing room air with a resistive inspiratory load of 8 kPa litre-1 s, PE'CO2 again increased significantly (P less than 0.05) following all three drugs. The increase in PE'CO2 after meptazinol was then the same as that after morphine (0.51 kPa averaged over 3.5 h). The increase following pentazocine (0.80 kPa) was significantly greater than that after both morphine and meptazinol (P less than 0.02).

Specific conductance using forced airflow oscillation in mechanically ventilated human subjects.

A method is described to measure specific airway conductance in mechanically ventilated patients. Airflow resistance (R) was measured continuously using the forced airflow oscillation method and plotted against volume during slow deflation of the lungs. The previously reported hyperbolic configuration of the resistance-volume curve was confirmed, but a nonlinear conductance-volume relationship was found that could be explained by a constant resistance (A) in series with the volume-dependent resistance of the lower airways. A computer-aided analysis of the resistance-volume curve determined the parameters of the hyperbola that best fitted the data and from this the volume-dependent conductance, Glaw = 1/(R - A), was calculated. This method consistently provided a very good fit to the data and resulted in a linear lower airway conductance-volume relationship in anesthetized and in awake subjects. The slope of this linear relationship (Glaw) was therefore independent of volume, and specific lower airway conductance was used as an index of bronchomotor tone. In awake subjects given bronchoconstrictor and bronchodilator aerosols, good correlation was shown between changes in specific conductance measured by this technique and by the standard plethysmographic method.

Prophylactic effect of aminophylline and salbutamol on histamine-induced bronchoconstriction.

The effect of salbutamol 200 micrograms aerosol, i.v. high-dose aminophylline 670 mg or placebo (aerosol and infusion) on bronchomotor tone were compared in normal volunteers before and after bronchial provocation with histamine aerosol 500 micrograms. The study was a double-blind cross-over design. Specific airways conductance of the lower airway (s. Glaw) was measured using a forced airflow oscillation technique. All subjects receiving aminophylline had tremor and irritability, whereas after salbutamol there were no noticeable systemic or psychological effects. Before the administration of histamine, salbutamol caused significant bronchodilatation compared with control: aminophylline did not induce a significant change in airway conductance. The effect of histamine administration on s. Glaw was only partially blocked by the high dose of aminophylline, but was completely blocked by salbutamol.

Effect of isoflurane on bronchomotor tone in man.

Twenty patients were anaesthetized with thiopentone, the trachea intubated and the lungs ventilated with 70% nitrous oxide and oxygen. Normocapnia was maintained and, following control measurements of the specific conductance of the lower airways (s.Glaw), either 1.7% isoflurane or 1.3% halothane was added to the inspired gas mixture, 10 patients receiving each drug. s.Glaw was measured repeatedly during the next 30 min. There was a tendency for s.Glaw to increase--indicating a reduction in bronchomotor tone--during the administration of isoflurane, the effect approaching statistical significance. The administration of halothane was associated with a significant increase in s.Glaw. There was a statistically significant increase in the expiratory reserve volume, and a decrease in mean respiratory resistance over the tidal range in both groups. These results indicate that isoflurane does not cause an increase in bronchomotor tone, and may have a tendency to decrease it. This suggests that the previously reported increase of respiratory resistance during isoflurane anaesthesia resulted from a reduction in lung volume, rather than a change in bronchomotor tone.

Enflurane anaesthesia causes graded changes in the brainstem and early cortical auditory evoked response in man.

The effect of increasing end-tidal enflurane concentration on the auditory evoked response was studied in six patients. After a standard induction, anesthesia was maintained with 70% nitrous oxide in oxygen and the end-tidal enflurane concentration was increased gradually from 0 to 1% over a period of 30 min. The averaged auditory evoked response was derived from the electroencephalogram and measurements were made of the latencies and amplitudes of waves I, III, V, Pa and Nb within the auditory evoked response. The latencies of all waves and the interpeak latencies I to V and III to V showed significant linear increases and the amplitudes of Pa and Nb showed significant linear decreases with increasing end-tidal enflurane concentration. These results could not be explained by changes in deep body temperature or end-tidal carbon dioxide concentration. The study demonstrated a dose-related direct effect of enflurane on the brainstem and early cortical components of the auditory evoked response.

Pronounced, episodic oxygen desaturation in the postoperative period: its association with ventilatory pattern and analgesic regimen.

The respiratory effects of two postoperative analgesic regimens were compared in two groups of 16 patients each, recovering from general anesthesia and major surgery. One group received a pain-relieving dose of iv morphine (mean, 18.1 mg), with the same dose repeated as a continuous intravenous infusion over the subsequent 24 h. The other group received regional anesthesia using bupivacaine. The patients were monitored for 16 h after surgery. The two analgesic regimens provided patients with comparable analgesia throughout the study period, but there were quite different respiratory effects in the two groups. Ten patients receiving morphine infusions had a total of 456 episodes of pronounced oxygen desaturation (SaO2 less than 80%). These occurred only while the patients were asleep, and all were associated with disturbances in ventilatory pattern, namely, obstructive apnea (144 episodes in eight patients), paradoxic breathing (275 episodes in six patients), and period of slow ventilatory rate (37 episodes in one patient). In contrast, in patients receiving regional anesthesia, oxygen saturation never decreased below 87%. Central apnea, obstructive apnea, and paradoxic breathing occurred more frequently in patients in the morphine group (12, 10, and 10 patients, respectively) than patients in the regional anesthesia group (4, 3, and 5 patients, respectively). The interaction of sleep and morphine analgesia produced disturbances in ventilatory pattern, causing profound oxygen destruction. These results suggest that postoperative pain relief using regional anaesthesia has a greater margin of safety in terms of respiratory side effects than does the continuous administration of opiates.

Late postoperative nocturnal dips in oxygen saturation in patients undergoing major abdominal vascular surgery. Predictive value of pre-operative overnight pulse oximetry.

Twenty-four patients (23 male) who presented for aortic reconstructive surgery were studied with pulse oximetry on a pre-operative night and during the first five postoperative nights. Patients with five or more dips in oxygen saturation of greater than 4% (with a prompt recovery back toward baseline of 3% or more) per hour of monitoring were classified as having a significant abnormality of respiration. Pre-operatively, four of 24 patients (17%) demonstrated such an abnormality. Postoperatively, 12 patients (50%) met these criteria on at least one of the first five postoperative nights and six of these had two or more nights with severe episodic hypoxaemia. Frequent severe episodic dips in arterial oxygen saturation (to less than 85% saturation) occurred in the late postoperative period at a time when oxygen therapy would usually have been discontinued. Pre-operative overnight pulse oximetry studies fail to predict the development of abnormal respiratory patterns in the postoperative period in the majority of patients.