Inspiratory respiratory mechanics estimation by using expiratory data for reverse-triggered breathing cycles.

BACKGROUND AND OBJECTIVE: Model-based lung mechanics monitoring can provide clinically useful information for guiding mechanical ventilator treatment in intensive care. However, many methods of measuring lung mechanics are not appropriate for both fully and partially sedated patients, and are unable provide lung mechanics metrics in real-time. This study proposes a novel method of using lung mechanics identified during passive expiration to estimate inspiratory lung mechanics for spontaneously breathing patients. METHODS: Relationships between inspiratory and expiratory modeled lung mechanics were identified from clinical data from 4 fully sedated patients. The validity of these relationships were assessed using data from a further 4 spontaneously breathing patients. RESULTS: For the fully sedated patients, a linear relationship was identified between inspiratory and expiratory elastance, with slope 1.04 and intercept 1.66. The r value of this correlation was 0.94. No cohort-wide relationship was determined for airway resistance. Expiratory elastance measurements in spontaneously breathing patients were able to produce reasonable estimates of inspiratory elastance after adjusting for the identified difference between them. CONCLUSIONS: This study shows that when conventional methods fail, typically ignored expiratory data may be able to provide clinicians with the information needed about patient condition to guide MV therapy.

Core body temperature is normal in chronic fatigue syndrome.

BACKGROUND: Subjects with chronic fatigue syndrome (CFS) frequently report symptoms of subnormal body temperature and low-grade fever. We conducted a study to determine whether CFS subjects manifest any abnormality of core body temperature (CBT) that might help explain their fatigue. METHODS: Continuous 24-hour recordings of CBT measured every 5 min were performed in 7 subjects meeting the Centers for Disease Control definition of CFS. Three additional groups were studied: normal controls, subjects with seasonal allergy, and subjects with major depression. Subjects (n = 7) in each group were age-, sex-, and weight-matched to the CFS group and had normal basal metabolic rates, thyroid function, and 24-hour urinary free cortisol excretions. CBT was measured with an ingestible radio frequency transmitter pill and a belt-worn receiver-logger. Each pill was factory-calibrated to +/- 0.1 degree C and field-calibrated with a water bath calibration prior to use. RESULTS: The 24-hour mean calibration-adjusted CBTs of each group were not significantly different (control: 37.00 +/- 0.17 degrees C; CFS: 37.04 +/- 0.31 degrees C; allergy: 37.15 +/- 0.18 degrees C; depression: 37.16 +/- 0.18 degrees C). Similarly, the mean peak and trough circadian temperatures were not statistically different. The mean 24-hour profile of CBT for each group showed a similar circadian rhythm. In simultaneously collected blood samples, each group showed a similar circadian profile of serum cortisol with a peak occurring at 08:00. CONCLUSIONS: Subjects with CFS have normal CBT despite frequent self-reports of subnormal body temperature and low-grade fever.

Alpha and beta adrenergic-induced renin release in man.

Changes in hemodynamic variables and renin release, induced with both alpha and beta adrenergic agonists, were studied in 5 normal men. Saline (0.9% NaCl), methoxamine (1.6 and 5.9 mug/kg/min), and isoproterenol (0.015 and 0.026 mug/kg/min) were infused individually in a random order for 30 min. Methoxamine and isoproterenol caused the predicted directionally opposite cardiovascular changes but caused nearly equal and dose-related increases in plasma renin activity, as measured by radioimmunoassay. Saline infusion had no effect. Propranolol (0.125 mg/kg) caused decreases in systolic pressure and heart rate, and a significant decrease in plasma renin activity. Propranolol prevented the renin-releasing effects of isoproterenol and methoxamine, but only the cardiovascular effects of isoproterenol. It appears that alpha or beta agonists stimulate renin release equally in man and that at least one step in renin is propranolol-sensitive. Such sensitivity may be independent of its beta receptor blocking activity.

Postural hypotension: adrenergic responsivity and levodopa therapy.

Four subjects with orthostatic hypotension were given intravenous infusions of methoxamine and isoproterenol. Methoxamine caused an elevation in systolic blood pressure. Isoproterenol resulted in a fall in blood pressure in three of the subjects. The heart rate decreased with methoxamine, but increased with isoproterenol. The responsivity in orthostatic hypotension was compatible with denervation supersensitivity. These effects were compared with the responsivity to methoxamine and isoproterenol of five labile hypertensives. Two patients with severe orthostatic hypotension were treated with regimens including levodopa. Levodopa alone would further aggravate postural hypotension. But in one subject given levodopa, ephedrine, and fludrocortisone and in the other managed on levodopa, tranylcypromine, and fludrocortisone, symptomatic orthostatic hypotension was successfully eliminated. These results support the usefulness of levodopa, in combination with adrenergic agents, as a therapeutic measure for advanced forms of orthostatic hypotension.

Administration of triazolam prior to recovery sleep: effects on sleep architecture, subsequent alertness and performance.

The effects of triazolam (0.125, 0.25, and 0.5 mg) versus placebo on recovery sleep staging, subsequent alertness and psychomotor performance were evaluated in humans. Forty-five healthy male subjects were deprived of sleep for 24 h, then administered a single dose of triazolam or placebo using a double-blind procedure. Subjects then attempted to obtain recovery sleep under non-sleep-conducive conditions (sitting upright in a well-lit, crowded chamber) for the next 6 h, followed by 18 more hours of sleep deprivation. During all sleep deprivation periods subjects were tested bihourly on a performance assessment battery which included symbol digit modalities tests (SDMT), four-letter search (FLS), logical reasoning (LR), time estimation (TE), visual vigilance (VV), and short term memory (STM) tasks. Sleepiness levels were measured objectively with multiple sleep latency tests (MSLT) and subjectively with the Stanford Sleepiness Scale (SSS). Compared to placebo, all doses of triazolam resulted in increased amounts of stage 3-4 sleep, and the 0.5 mg dose significantly reduced awakenings (Ps less than 0.05). Although subjects receiving triazolam averaged 21-42 min more total sleep time (TST) than subjects receiving placebo, differences in TST were not statistically significant. Apparent triazolam-mediated benefits to sleep quality resulted in no obvious improvements in performance or alertness levels during subsequent sleep deprivation. It was concluded that the increases in stage 3-4 sleep amounts were most likely due to triazolam-mediated increases arousal thresholds, and the triazolam mediated changes in sleep parameters obtained in the present study were not indicative of substantial changes in the recuperative value of sleep.

Relationships of the renin-angiotensin-aldosterone system and sodium balance to blood pressure regulation in chronic renal failure of polycystic kidney disease.

In 5 patients with polycystic kidney disease and creatinine clearances ranging from 4 to 40 ml/min, relationships between changes in blood pressure, sodium balance, body fluid compartments, plasma renin activity (PRA), urinary aldosterone excretion, and plasma aldosterone concentrations were studied during periods of low, medium, and high sodium intake. Total body water (TBW), total exchangeable body sodium (TEBS), and extracellular volume (ECV) were measured by isotope dilution techniques, plasma volume with Evan's blue dye, and PRA and aldosterone by radioimmunoassay. Low sodium intake reduced kidney function, blood pressure, and serum sodium, while PRA reached its highest levels. Subsequent increases in sodium intake improved kidney function and increased blood pressure. Plasma volume increased slightly and ECV markedly, while PRA dropped to 15 percent of the value noted after the low sodium intake. TBW and TEBS showed inconsistent changes. Aldosterone changes correlated closely with PRA. Blood pressure showed a negative correlation with PRA, but a positive one with body weight and cumulative sodium balance, and with plasma and extracellular volumes.it is suggested that whereas renin and aldosterone are involved in the maintenance of circulatory homeostasis during sodium loss, sodium retention causes an increase in blood pressure by concomitant changes in body fluids.

Triazolam impairs learning and fails to improve sleep in a long-range aerial deployment.

Of the soldiers deployed from the 18th Airborne Corps, Ft. Bragg, NC, on the Army's annual field exercise in the Middle East (Operation Brightstar) 68 received either placebo or 0.5 mg of triazolam once airborne on the first leg of their journey from the U.S. to the Middle East. Sleep and activity were measured during the flight by means of a wrist-worn activity monitor. Cognitive performance, mood, and sleepiness were measured 8 h after drug administration during a refueling stop in Europe. Triazolam did not increase the duration or improve the continuity of sleep during the 8-h flight from the U.S. to the refueling point. The scheduling of an inflight meal contributed to this lack of effect. There were no differences in mood or sleepiness between the two groups as assessed by the Profile of Mood States and the Stanford Sleepiness Scale. Ability to recall verbal material presented immediately prior to testing was impaired by triazolam 8 h after ingestion, as evidenced by fewer items recalled on the Logical Memory portion of the Wechsler Memory Scale. These results suggest that triazolam at a dose of 0.5 mg is unsuitable for use in long-range aerial deployments when unimpaired cognitive functioning is required immediately upon arrival.

Postanesthetic monitoring of core body temperature using telemetry in North American river otters (Lutra canadensis).

Remote thermal telemetry was performed on North American river otters (Lutra canadensis) during the 1995 North Carolina Wildlife Resources Commission Otter Restoration Project. Otters were anesthetized with either ketamine-midazolam (n = 11) or tiletamine-zolazepam (n = 9) combinations. Based upon initial rectal temperatures, mild to moderate hyperthermia (39.4-40.5 degrees C) developed in five otters given ketamine-midazolam and three otters given tiletamine-zolazepam. Following anesthetic induction, each otter received an ingestible temperature transmitter. Dependent upon gastrointestinal transit time and transmitter battery life, core body temperature was monitored for up to 13.75 hr postanesthesia. Thermal telemetry revealed a gradual decline in core temperature in all otters after anesthetic recovery (30-60 min). Median core temperature stabilized subsequently within 0.3 degrees C of resting temperature (38.4 degrees C) 1.75 hr after initial injection in otters given tiletamine-zolazepam and 2.75 hr in otters given ketamine-midazolam. Minor fluctuations in body temperature (less than 1 degree C) occurred in most otters from 6 to 13.75 hr and were attributed to variations in physical activity.

The impact of water temperature on core body temperature of North American river otters (Lutra canadensis) during simulated oil spill recovery washing protocols.

Ten North American river otters (Lutra canadensis) were anesthetized with Telazol and instrumented with ingestable radiotelemetry temperature sensors for measuring core body temperature. The otters were then subjected to a washing protocol to simulate rehabilitation following an oil spill contamination. This protocol consisted of a 30-min wash in a 1:16 dilution of dishwashing liquid using either cold (24 degrees C) water or water near baseline core body temperature (38.4 degrees C), followed by a 30-min rinse with water of the same temperature, followed by 10 min of forced hot air drying. Core body temperatures of the otters washed in cold water fell at a median rate of 0.1 degrees C/min, whereas otters washed in warm water maintained stable core temperatures until the completion of the protocol, at which time their core temperatures began to drop at a similar rate. Core temperatures restabilized in both groups, and no statistical difference in core temperature between groups remained 180 min after initiation of the protocol. Efforts to examine the efficacy of supplemental squalene administration to speed the recovery of fur condition and waterproofing were unsuccessful because the washing protocol did not cause loss of coat waterproofing in 8 of the 10 subjects.

Behavioral medicine approaches to hypertension: an integrative analysis of theory and research.

This article compares behavioral and biological approaches to hypertension, highlights some of the practical, semantic, and theoretical issues involved, and attempts a constructive, behavioral medicine integration of these approaches. The major behavioral approaches to hypertension are described, with a focus on their conceptual limitations as stimulants to research into psychobiological mechanisms. A biobehavioral systems analysis of hypertension is outlined, emphasizing the role of the central nervous system as a common pathway relating environmental and behavioral factors to cardiovascular regulatory dynamics and disease. Schwartz's concept of blood pressure disregulation is discussed, by which behavioral "feedback loops" may be included in the pathogenesis of homeostatic disorders. A detailed discussion of concepts underlying the clinical pharmacological approach to hypertension is provided; parallels are drawn between the conceptual framework and the theoretical and practical questions facing behavioral researchers concerned with hypertension. Synergistic interactive effects of drug and behavioral treatments are proposed. A biobehavioral overview, which links pressor and depressor stimulus patterns to both pathogenesis and therapy, can serve to integrate the previous biobehavioral systems analysis, the conceptual framework of clinical pharmacology, and the notion of biobehavioral disregulation of blood pressure. Implications for future behavioral medicine research in hypertension are provided.

Treatment of severe hypertension with minoxidil.

Minoxidil in daily doses of 6 to 40 mg was administered to 11 patients with severe hypertension. Two patients died of causes unrelated to the drug and one patient withdrew from the study. Blood pressure was controlled in the remaining eight subjects, who received the drug for periods ranging from 5 to 40 months. In three patients minoxidil could subsequently be replaced by conventional antihypertensive therapy. Adverse effects of minoxidil included fluid retention (as assessed by edema and plasma volume studies), nonspecific ECG changes, hypertrichosis and conjunctival redness. Concomitant administration of diuretic and beta-adrenergic blocking agents resulted in excellent tolerance of the treatment and high patient compliance.

The effect of exercise on atropine pharmacokinetics.

Seven healthy males (19-32 y) underwent each of four separate conditions in a repeated measures design. Five of these subjects underwent an additional trial. In four of five trials subjects received 2.0 mg atropine sulfate intramuscularly in the anterolateral portion of the left thigh: at rest (T1); following completion of a single exercise (Ex) bout (T2), (Each bout consisted of 25 min of stationary cycling at 40% VO2 max with 5 min of seated rest), prior to three Ex bouts (T3) and following one and prior to three Ex bouts (T5). Trial 4 (T4) was the same as T3 with the substitution of a saline placebo. Serum samples were collected over a 12 h period and atropine concentration was determined by RIA. Ex trials were compared to T1. Ex prior to atropine (T2) significantly decreased the mean volume of distribution (Vz, 278 vs 232 l). Ex in T3 significantly decreased the serum half life (t1/2, 4.2 vs 3.5 h), Vz (278 vs 198 l), and clearance (CL, 763 vs 638 ml.min-1) and significantly increased the peak concentration (Cp, 6.7 vs 12.3 ng.ml-1) and area under the curve (AUC, 44.1 vs 53.1 ng.ml-1). In T5, Ex significantly decreased the t1/2 (3.4 h), Vz (182 l) and CL (575 ml.min-1) and significantly increased the absorption rate constant (ka, 0.482 vs 1.1 min-1), elimination rate constant (ke, 0.0012 vs 0.0015 min-1), Cp (14 ng.ml-1) and AUC (53.3 ng.h.ml-1). These results demonstrate that moderate Ex either prior to and/or immediately following drug administration has the capacity to significantly modify atropine pharmacokinetics.

Circadian rhythm of core body temperature in subjects with chronic fatigue syndrome.

The pathophysiological basis for chronic fatigue syndrome (CFS) remains poorly understood. Certain symptoms of CFS, namely fatigue, neurocognitive symptoms and sleep disturbance, are similar to those of acute jet lag and shift work syndromes thus raising the possibility that CFS might be a condition associated with disturbances in endogenous circadian rhythms. In this study, we tested this hypothesis by examining the circadian rhythm of core body temperature (CBT) in CFS and control subjects. Continuous recordings of CBT were obtained every 5 min over 48 h in a group of 10 subjects who met the Center for Disease Control (CDC) definition of CFS and 10 normal control subjects. Subjects in the two groups were age, sex and weight-matched and were known to have normal basal metabolic rates and thyroid function. CBT recordings were performed under ambulatory conditions in a clinical research centre with the use of an ingestible radio frequency transmitter pill and a belt-worn receiver-logger. CBT time series were analysed by a cosinor analysis and by a harmonic-regression-plus-correlated-noise model to estimate the mean, amplitude and phase angle of the rhythm. The goodness of fit of each model was also compared using the Akaike Information Criterion (AIC) and sigma2. Average parameters for each group were compared by Student's t-test. By cosinor analysis, the only significant difference between CFS and control groups was in the phase angle of the third harmonic (P=0.02). The optimal harmonic-regression-plus-correlated-noise models selected were ARMA(1,1): control 7, CFS 6; ARMA(2,0): control 1, CFS 4; and ARMA(2,1): control 2 subjects. The optimal fit ARMA model contained two harmonics in eight of 10 control subjects but was more variable in the CFS subjects (1 harmonic: 5 subjects; 2 harmonics: 1 subject; 3 harmonics: 4 subjects). The goodness of fit measures for the optimal ARMA model were also better in the control than the CFS group, but the differences were not statistically significant. We conclude that, measured under ambulatory conditions, the circadian rhythm of CBT in CFS is nearly indistinguishable from that of normal control subjects although there was a tendency for greater variability in the rhythm. Hence, it is unlikely that the symptoms of CFS are because of disturbance in the circadian rhythm of CBT.