Effects of bright light and melatonin on sleep propensity, temperature, and cardiac activity at night.

Melatonin increases sleepiness, decreases core temperature, and increases peripheral temperature in humans. Melatonin may produce these effects by activating peripheral receptors or altering autonomic activity. The latter hypothesis was investigated in 16 supine subjects. Three conditions were created by using bright light and exogenous melatonin: normal endogenous, suppressed, and pharmacological melatonin levels. Data during wakefulness from 1.5 h before to 2.5 h after each subject's estimated melatonin onset (wake time + 14 h) were analyzed. Respiratory sinus arrhythmia (cardiac parasympathetic activity) and preejection period (cardiac sympathetic activity) did not vary among conditions. Pharmacological melatonin levels significantly decreased systolic blood pressure [5.75 +/- 1.65 (SE) mmHg] but did not significantly change heart rate. Suppressed melatonin significantly increased rectal temperature (0.27 +/- 0.06 degrees C), decreased foot temperature (1.98 +/- 0.70 degrees C), and increased sleep onset latency (5.53 +/- 1.87 min). Thus melatonin does not significantly alter cardiac autonomic activity and instead may bind to peripheral receptors in the vasculature and heart. Furthermore, increases in cardiac parasympathetic activity before normal nighttime sleep cannot be attributed to the concomitant increase in endogenous melatonin.

Attenuation of sleep propensity, core hypothermia, and peripheral heat loss after temazepam tolerance.

If changes in thermoregulation mediate sleepiness induced by sedative/hypnotics, then a reduction in the soporific efficacy (tolerance) of these agents may be accompanied by a concomitant reduction in their thermoregulatory effects. We compared the thermoregulatory and soporific effects of acute temazepam (30 mg at 1400) in 11 young male subjects before and immediately after 7 consecutive days of temazepam (30 mg). Subjects lay supine (0800-2030), while foot (T(ft)) and rectal (T(c)) temperatures were recorded. Sleep onset latency (SOL) was measured hourly using 20-min multiple sleep latency tests. Relative to placebo, temazepam significantly reduced both T(c) and SOL (-0.31 degrees C and 14.1 min) while increasing T(ft) (3.39 degrees C). A significant tolerance developed after the week of temazepam, with a mean reduction in soporific efficacy of 4.0 +/- 0.8 min. This was accompanied by a concomitant attenuation in both T(c) (-0.16 degrees C) and T(ft) (1.44 degrees C). Furthermore, SOL was temporally related to T(ft) and the maximum rate of decline in T(c) before and after tolerance. Together, these results indicate that the thermoregulatory system may be functionally involved in the regulation of sleepiness.

Peripheral heat loss: a predictor of the hypothermic response to melatonin administration in young and older women.

Core hypothermia following daytime melatonin administration typically displays significant interindividual variability. As this hypothermia has been associated with significant increases in skin temperature, the mechanism by which melatonin decreases core temperature may involve increasing peripheral heat loss. If so, the interindividual variability in this effect may reflect concomitant interindividual variability in heat loss capacity at the distal periphery. For six younger (mean +/- SEM: 23.4 +/- 0.3 years) and 10 older women (mean +/- SEM: 65.6 +/- 0.7 years), the maximum decrease in core body temperature following a 5-mg (p.o.) dose of melatonin was correlated with the capacity to lose heat. This was determined by the maximum increase in contralateral hand temperature following a mild positive thermal challenge (PTC). The regression analysis yielded a significant (p < 0.01) correlation of 0.80, suggesting that the individual magnitude of hypothermia following melatonin administration may reflect the capacity of an individual to dissipate heat at the distal periphery.

Daytime melatonin and temazepam in young adult humans: equivalent effects on sleep latency and body temperatures.

1. As changes in core body temperature are generally associated with concomitant changes in sleep propensity, it is possible that the effects of hypnotic/soporific agents may be related to changes in thermoregulation. Therefore, to increase our knowledge of the mechanisms by which these agents exert their soporific effects, we compared the thermoregulatory and soporific effects of temazepam (20 mg per os (p.o.)) with those of melatonin (5 mg p.o.) when administered at 14.00 h to 20 young healthy adults (13 male, 7 female; age, 23.5 +/- 0.4 years). 2. From 08.00 to 20.30 h, subjects lay in bed, and foot and rectal (Tc) temperatures were recorded. Sleep onset latency (SOL) was measured using 20 min multiple sleep latency tests, performed hourly from 11.00 to 20.00 h, during which time heart rate was recorded. 3. Compared with placebo, both melatonin and temazepam significantly reduced Tc (-0.17 +/- 0.02 and -0.15 +/- 0.03 C, respectively) and SOL (by 4.8 +/- 1.49 and 6.5 +/- 1.62 min, respectively). Although both treatments significantly increased heat loss, only melatonin demonstrated cardiac effects. Importantly, there was a temporal relationship between minimum SOL and the maximum rate of decline in Tc for both melatonin (r = 0.48) and temazepam (r = 0.44). 4. A possible role of thermoregulation in sleep initiation is suggested by the similar temporal relationship between Tc and SOL for two different classes of soporific agents.

The effect of pre-operative oral fluids on morbidity following anaesthesia for minor surgery.

Postoperative morbidity and serum osmolality were studied in 46 patients who were encouraged to drink water until 3 h pre-operatively and 49 receiving the normal fasting regimen prior to minor surgery. There was significantly less thirst in the postoperative period in those patients allowed to drink and subjectively better recovery than after previous anaesthesia. There was no morbidity from ingestion of up to 11 of water 2.5 h pre-operatively. Although there was only a moderate improvement in postoperative recovery we feel that allowing patients to drink water pre-operatively improves patient comfort, especially since patients may have to fast for much longer than guidelines recommend, simply because of the traditional organisation of operating lists.

A system for audit of obstetric anaesthesia.

A modification to a computer based system of audit, widely used in anaesthesia for general surgery, is described, which permits a more detailed analysis of obstetric anaesthetic workload. By adjusting entries, in the operation input field, further information can be collected automatically. This allows the total number of regional anaesthetic procedures, including those in patients with epidurals for labour who progressed to caesarean section, to be calculated. It identifies the total number of caesarean sections, including anaesthetic technique and whether an epidural catheter was, in any case, present. This modification may be applicable to other computerised audit systems.

Chemically blocked analog assays for free thyronines. II. Use of equilibrium dialysis to optimize the displacement by chemical blockers of T4 analog and T3 analog from albumin while avoiding displacement of T4 and T3 from thyroxin-binding globulin.

Chemical blockers used to displace thyronine analog from albumin in analog kits for assay of free thyroxin (FT4) or free triiodothyronine (FT3) may also displace thyroxin (T4) or triiodothyronine (T3) from thyroxin-binding globulin (TBG), resulting in an apparent TBG dependence of results of free hormone estimates. We used equilibrium dialysis and antibody binding to assess the displacement of thyronine analogs and thyronines from albumin and TBG by use of chemical blockers. We chose a combination of two chemical blockers, which eliminated thyronine analog-albumin binding but minimized thyronine displacement from TBG for use in FT4 and FT3 assays. These blocked-analog free-hormone assays yielded accurate clinical results in euthyroid patients, hypo- and hyperthyroid patients, and in pregnant women. FT4 results were not entirely normalized in all nonthyroidally ill patients, indicating that decreased analog-albumin binding is not the only factor resulting in low FT4 results. In current Diagnostic Products Corp. (DPC) FT4 and FT3 blocked-analog kits, the blocker concentrations are the same as we used in these assays.

Chemically blocked analog assays for free thyronines. I. The effect of chemical blockers on T4 analog and T4 binding by albumin and by thyroxin-binding globulin.

Analog assays for free thyroxin (FT4) produce inaccurate results because the T4 analog is sequestered by albumin. Diagnostic Products Corp. (DPC) introduced the concept of chemically blocking analog-albumin binding in 1982. While DPC succeeded in eliminating albumin dependence, their 1985 version of chemically blocked FT4 assay appeared to be "thyroxin-binding globulin" (TBG) dependent, producing inappropriately low FT4 results with low TBG concentrations and high results with high TBG concentrations. We examined the effects of chemical blockers on albumin and TBG binding, using equilibrium dialysis to measure free fractions of T4 analog and T4. We then created FT4 assays in which various concentrations of chemical blockers were used to demonstrate their effects on FT4 estimates in patients with low or increased TBG concentrations or who were pregnant. We found that chemical blockers do displace T4 analog from albumin, but also displace T4 from albumin and, in high concentrations, from TBG as well. It is this displacement of T4 from TBG by chemical blockers that resulted in "TBG dependence" of DPC FT4 estimates. This problem has been corrected in currently available versions of the DPC FT4 kit.

Estimation of free thyroxin with a new thyroxin analog and a porous-glass solid phase.

We evaluated a new thyroxin analog-based assay for free thyroxin (FT4) (Corning Medical), finding it technically simple and precise (between-assay CVs of 3.3 and 4.2% for FT4 concentrations of 12 and 25 ng/L, respectively). We measured FT4 in a total of 325 serum samples from euthyroid patients; patients receiving replacement thyroxin; patients receiving estrogens or who were pregnant; hyperthyroid, hypothyroid, and non- thyroidally ill patients; and patients receiving salicylates, phenytoin, or heparin. This assay clearly identified hyper- and hypothyroid patients, and produced similar results in euthyroid patients with above-normal, normal, or low concentration of thyroxin-binding globulin. Results in some non-thyroid-illness patients and patients receiving salicylates or phenytoin were low compared with euthyroid patients receiving no medications, but the diagnostic accuracy of the Corning FT4 assay exceeded that of another analog-based assay (Amersham) in these particular groups. We believe the new Corning analog FT4 assay offers an attractive alternative to other commercial FT4 systems.

Evaluation of an immunoextraction procedure for the estimation of free thyroxine concentration.

We have examined the performance of a commercial free-thyroxine assay in which a radiolabeled T4 derivative permits the competitive quantitation of extracted T4 in the presence of serum proteins. After the total T4 pool had been radiolabeled with either I-125 T4 or I-131 T4, the solid-phase antibody was found to be associated with 4-8% of the total T4 present in the assay tube. Of this, 15-60% was displaceable (antibody-bound). The assay estimated free T4 to be 0.6-1.8 ng/dl in euthyroid patients, and distinguished them from hyperthyroid (sensitivity 91%) and hypothyroid patients (sensitivity 91%) without apparent TBG dependence. In patients with severe nonthyroidal illnesses, the assay correctly quantitated a reduced extracted mass in some. In other patients, however, the assay results were inappropriately lower than the actual extracted mass, in agreement with the FTI but not with the measurements of free T4 by dialysis. This assay appears to produce clinically appropriate results in most patients. In some nonthyroidally ill patients however, the indicated free T4 is spuriously low.

Creatine kinase B subunit as measured with a radioimmunoassay kit in detection of acute myocardial infarction.

Results with a commercial radioimmunoassay (RIA) reagent kit for quantification of the creatine kinase B subunit (CK-B) (Nuclear-Medical Laboratories, Irving, TX 75061) were compared with results obtained by electrophoresis for patients consecutively admitted to our coronary care unit for suspected acute myocardial infarction. Analytical sensitivity, precision, and specificity of the RIA were satisfactory. Its clinical efficacy was assessed in 97 patients suspected of having had an acute myocardial infarction. Of 30 patients who had had an acute myocardial infarction, increased CK-B was detected by RIA in 30 and by electrophoresis in 27. The temporal relationship between CK-B by RIA and CK-MB by electrophoresis was similar. Of 66 admissions where infarction was not established, CK-B was negligibly increased in samples from four patients by RIA, and from one by electrophoresis. Although not abnormally increased (greater than 5 U/L), CK-MB was detected by electrophoresis in samples from another five of these 66 patients. We conclude that estimation of CK-B by this RIA is an excellent alternative to estimation of CK-MB by electrophoresis in patients suspected of having had an acute myocardial infarction.