Effects of cocaine and d-amphetamine on sustained and selective attention in rats.

The effects of cocaine and d-amphetamine were compared in two attention-loading tasks. Cued by the position of a light, rats were food-reinforced for pressing one of two levers in a 2-choice, discrete-trial procedure. In the "sustained attention" task, the cue light was illuminated for a brief period (1.8 sec or less) at the beginning of each trial. In the "selective attention" task, the cue light remained on until a level press, while a blinking light over the incorrect lever served as a distractor. In the sustained attention task, low doses of d-amphetamine (0.25 mg/kg SC) and cocaine (2.5 mg/kg SC) enhanced accuracy; some doses of d-amphetamine (0.75 mg/kg SC) and cocaine (1.25 and 2.5 mg/kg SC) also reduced choice latencies. In the selective attention task, the lower doses of these drugs had no effect on accuracy, the highest dose of d-amphetamine (1.25 mg/kg SC) disrupted accuracy, and all doses of the drugs reduced choice latencies. The time to retrieve food was increased in a dose-dependent fashion by both drugs in both tasks. These results indicate that, other than differences in potency, cocaine and d-amphetamine induce similar behavioral effects in attention-loading tasks, with improvement or interference with performance dependent on the dose and the type of attention demanded of the task.

Symptoms of insulin-induced hypoglycemia in normal subjects.

In order to better characterize the psychobiology of hypoglycemic symptom production, six normal subjects had physiological/biochemical and symptom ratings at 20, 30 and 40 min after six different doses of intravenous regular insulin (0.0, 0.5, 1.0, 2.0, 3.0 and 4.0 units, in a Latin-square design); subjects also indicated after each dose whether they believed they had received an active or an inactive substance. Choice response switched from inactive to active substance when plasma glucose fell to the mid to high 50s mg/dl (i.e. whole blood glucose of approximately 50), and plasma epinephrine levels rose to between 100 and 200 pg/ml. Adrenergic symptoms and 'weakness' were most strongly associated with choice; other symptom variables had weaker associations. Symptoms were more strongly correlated with epinephrine than glucose levels, but anxiety was not strongly correlated with the epinephrine increases.

Endocrine and physiological changes during "spontaneous" panic attacks.

Eight patients with DSM-III-defined panic attacks were compared to four normal subjects on hormonal and physiological variables measured at six predetermined times through 24 hr and also during nine "spontaneous" attacks. Levels at predetermined times were not different, other than a reduction of urinary unconjugated epinephrine in patients. Plasma prolactin was elevated at the peak of most of the attacks and correlated with attack severity. Plasma cortisol and growth hormone, and heart rate, were elevated during some attacks, and plasma norepinephrine showed small increases. Significant plasma epinephrine and MHPG changes were not observed.

Cholecystographic agents and sulfobromophthalein inhibit the binding of L-thyroxine to plasma membranes of rat hepatocytes.

Cholecystographic agents and sulfobromophthalein (BSP) cause a major discharge of labeled T4 from the liver in man in vivo. In the present study we sought to determine if this discharge is partially due to inhibition of T4 binding to plasma membrane sites. Plasma membranes were isolated from hepatocytes of female Sprague-Dawley rats, and 5'-nucleotidase levels were measured to demonstrate plasma membrane viability. Specific binding of T4 (Ka, 1.01 X 10(8) M) was confirmed by displacement of labeled T4 by unlabeled hormone (10(-10)-10(-5) M). Displacement of labeled hormone was also produced by addition of tyropanoate, iopanoate, ipodate, or BSP. At 5-mM concentrations of inhibitor, the Ka for T4 declined to 4.00 X 10(7) M with BSP, 5.07 X 10(7) M with ipodate, 5.62 X 10(7) M with tyropanoate, and 7.43 X 10(7) M with iopanoate. Thus, a portion of the discharge of hepatic T4 after administration of these agents may be due to competitive inhibition of binding to plasma membrane sites.

Evaluation of plasma 3-methoxy-4-hydroxyphenylglycol.

A high-performance liquid chromatographic (HPLC) assay suitable for the evaluation of 3-methoxy-4-hydroxyphenylglycol (MHPG) in 1-ml aliquots of plasma is presented. Preparatory steps include extraction into ethyl acetate and minicolumn chromatography. Recoveries are monitored with [3H]MHPG. The HPLC procedure utilizes a C18 column, isocratic elution and amperometric detection. The assay was checked against a gas chromatographic-mass spectrometric procedure; the two procedures correlated well with a correlation coefficient of 0.99. Intra-assay reproducibility was 5.4%, inter-assay reproducibility 10.7%. Immediate changes in the orthostatic position did not affect the plasma MHPG concentration. Based on 22 normal controls the daytime plasma MHPG level was 2.98 +/- 0.66 ng/ml (mean +/- S.D.).

Salivary estriol as an index to fetal wellbeing.

We adapted two commercially available kits for measuring serum estriol to use in assaying salivary estriol in the third trimester of pregnancy. Salivary estriol increases during gestation, as does unconjugated estriol in serum. With a meticulous collection protocol, fetal wellbeing can be monitored as successfully with saliva samples as with serum. A fetal demise was charted similarly by the salivary and the serum estriol assay. Inter- and intra-assay reproducibility (CV) of the saliva assay was 6.2%. Day-to-day CV, based on a fasting sample before breakfast but obtained 1 to 3 h after rising, was 14.8% (SD 5.8%). Values for salivary estriol obtained immediately after ingestion of food or drink dropped by 19.0% (SD 17.9%) and 32.1% (SD 21.9%), respectively, as compared with values determined immediately before intake of food or water.

Anxiety and epinephrine in multiparous women in labor: relationship to duration of labor and fetal heart rate pattern.

The duration of labor in multigravid subjects in phase 1 labor at term (from 3 to 6 cm of cervical dilatation; mean duration = 2.7 hours) was significantly related to measures of plasma epinephrine and norepinephrine obtained at the onset of the phase (n = 50). Epinephrine was significantly related to observer ratings of subject stress and the scores from the three dimensions of our self-report Labor Anxiety Inventory. The fetal heart rate pattern in phase 2 labor (7 to 10 cm of cervical dilatation; mean duration = 1.2 hours) was significantly related to phase 1 measures of epinephrine, observed stress, and two of the anxiety dimensions (n = 44 to 47). The results provide support for the hypotheses that, under normal clinical conditions, several types of patient anxiety are related to catecholamine levels and that anxiety and epinephrine are related to duration of labor and fetal well-being. The results suggest that medical/nursing evaluation and management of patient anxiety should include a self-report measure of three dimensions of anxiety (coping, safety, and pain), which are relatively independent of observed physical stress and which may relate to maternal labor progress as well as fetal heart rate pattern.

Endocrine and cardiovascular responses during phobic anxiety.

In vivo exposure therapy for phobias is uniquely suited for controlled studies of endocrine and physiologic responses during psychologic stress. In this study, exposure therapy induced significant increases in subjective anxiety, pulse, blood pressure, plasma norepinephrine, epinephrine, insulin, cortisol, and growth hormone, but did not change plasma glucagon or pancreatic polypeptide. Although the subjective and behavioral manifestations of anxiety were consistent and intense, the magnitude, consistency, timing, and concordance of endocrine and cardiovascular responses showed considerable variation.

Urinary catecholamines and mitral valve prolapse in panic-anxiety patients.

Free norepinephrine and epinephrine were measured in two consecutive 12-hour urine collections gathered during normal activity and sleep from 23 panic-anxiety patients and 9 normal subjects. Mitral value prolapse (MVP) was found in 7 of 20 patients who had echocardiograms. Mean nighttime norepinephrine and epinephrine excretion in panic-anxiety patients without MVP was significantly higher than that of control subjects, and was significantly higher than that of anxiety patients with MVP. In the daytime, all groups had higher catecholamine (CA) levels, but the differences between the groups were less pronounced. Medication significantly relieved symptoms and was associated with decreased CA levels. Elevated basal CA levels may characterize the subgroup of panic-anxiety patients who do not have MVP.

Adrenergic function in patients with panic anxiety.

Increased beta-adrenergic receptor sensitivity could account for many aspects of panic disorder. We tested this hypothesis by comparing 14 patients with six normal control subjects. The controls and eight patients had 14 blood samples taken, and heart rate and BP measured, during a four-hour protocol that included supine rest, a posture and isometric exercise stimulus, and a series of up to seven logarithmically increasing bolus intravenous doses of isoproterenol hydrochloride. The other six patients were studied only at rest. Patients had markedly elevated resting heart rate, substantially elevated levels of plasma epinephrine, cortisol, and growth hormone, mildly elevated plasma norepinephrine levels, and decreased heart rate responses to isoproterenol. These results suggest that beta-adrenergic receptor response is not increased, and may be decreased, in patients with panic disorder. Receptor down-regulation could result from the increased adrenergic function that these patients demonstrate, even in the absence of panic attacks.

Serum testosterone measurements.

Serum testosterone and especially free testosterone is one of the parameters commonly used to evaluate androgen excess or deficiency. The authors equilibrated serum samples with 14C-labeled testosterone followed by an ammonium sulfate precipitation to compare the "apparent free testosterone concentration" with "total" serum testosterone concentration in the following populations: normal males and females; females presenting with gynecologic problems, particularly hirsutism and/or virilization; and males and females on maintenance hemodialysis. Total serum testosterone for each specimen was assayed with five different commercially available RIA kits encompassing a variety of technics: direct assay technics, assays utilizing extraction procedures prior to RIA; tritium-labeled tracer as well as iodine-labeled tracers. Clinical correlations improve strikingly when apparent free testosterone concentrations rather than total serum testosterone concentrations are used.

In vivo platelet aggregation and plasma catecholamines in acute myocardial infarction.

In vivo platelet aggregation assessed with the Filtragometer and potential correlates were compared among (1) patients with acute myocardial infarction (AMI), (2) normal controls, (3) patients with acute chest pain in whom AMI was eventually ruled out (ROMI), and (4) chronic outpatients (Cardiac Clinic group) with a history of myocardial infarction and/or angina pectoris. The measure was independent of sex, age, platelet count, immediate food intake, serum cholesterol, and triglyceride levels. The AMI group showed higher in vivo platelet aggregation than any of the other three groups (p less than 0.01). Least in vivo aggregation was seen in the normal group. Despite lack of correlation with the platelet aggregation measure, plasma epinephrine and norepinephrine showed statistically significant differences between the AMI and each of the other three groups. Our data support an association between platelet function and AMI, although not necessarily a cause and effect relationship.

X-linked spondyloepiphyseal dysplasia tarda: mucopolysaccharide excretion studies.

Sex linked spondyloepiphyseal dysplasia tarda is described in a family with four affected members. The characteristic features of short trunk, hip disease, and flattening of the vertebrae with a posterior "hump" were present. Urinary mucopolysaccharides were characterized both quantitatively and qualitatively and were within normal values.

Radioimmunoassay of serum parathyrin: comparison of five commercial kits.

We compared serum parathyrin radioimmunoassay data obtained with five commercially available kits for normal subjects, patients on dialysis, and patients with hyperparathyroidism. The Cambridge Nuclear kit gave low results, did not distinguish the dialysis-group sera from the normal sera, and had the greatest CV (56%) both inter- and intra-assay. The Immuno Nuclear PTH-II kit gave more satisfactory clinical data than their PTH-C-terminal kit; however, as with most procedures involving a substantial and variable nonspecific binding correction for each serum, parallelism between samples and the standard curve was poor, turnaround time slow, and inter-assay CV high (39%). Unlike the other kits, the Nichols and the Iso-Tex products depend on a direct methodology; they displayed good parallelism and distinguished among our three populations. A Scatchard plot of results with the Nichols kit was closest to the ideal linear model; the Iso-Tex kit had the shortest turnaround time.

Radioimmunoassay for plasma thromboxane B2.

Platelet activity may play a major role in the acute phase of atherosclerotic cardiovascular disease. To assess such activity, an assay for plasma thromboxane B2, a prostaglandin metabolite unique to platelets, is needed. The radioimmunoassay described here is based on a nonequilibrium incubation followed by a solid-phase second-antibody separation of bound from free thromboxane B2. No prior purification is required. Values for 22 normal subjects averaged 39.0 (SD 24.6) ng/L. The thromboxane B2 concentration of a plasma sample was 20.3 ng/L as compared with 37 micrograms/L in the corresponding serum. Plasma thromboxane B2 concentrations before and after ingestion of aspirin differed significantly (p less than 0.025). The biological half-life of intravenously injected [3H]thromboxane B2 in rabbits was 20 min. At the end of 2 h, 85% of the label was accounted for in urine, 7% in liver, and 5% in lung. Our assay is simple, reproducible, sensitive, and specific. It can be used to reflect acute events involving platelet aggregation.

Maternal psychological and physiologic correlates of fetal-newborn health status.

Data were obtained from 32 primigravid women in pregnancy and in labor. Anxiety in labor, measured by a self-report inventory, and plasma epinephrine were significantly correlated with the fetal heart rate pattern in active-phase labor (3 to 10 cm of cervical dilatation). The fetal heart rate pattern was significantly correlated with Apgar scores at 1 and 5 minutes. Conflict in the acceptance of pregnancy, measured in prenatal interviews, predicted anxiety and epinephrine levels in labor and the 5-minute Apgar score.

The relationship of maternal prenatal development to progress in labor and fetal-newborn health.

A study of 32 normal married primigravidas was conducted to determine the relationships among maternal psychological and physiological variables, subsequent progress in labor, and the health status of the fetus and neonate. At the onset of phase 2 of labor (3 cm of cervical dilatation), self-reported anxiety and endogenous plasma epinephrine were significantly correlated. With the deletion of subjects to control for the effect of medications, higher epinephrine levels were significantly associated with lower uterine contractile activity at the onset of phase 2 and with longer labor in phase 2 (3-10 cm of cervical dilatation). Psychological variables measured in pregnancy correlated significantly with the variables measured at the onset of phase 2 labor. Conflict concerning the acceptance of pregnancy showed the most significant relationships to the phase 2 labor variables, with correlations of 0.39 for anxiety, 0.59 for plasma epinephrine, -0.70 and -0.52 for the two adjacent Montevideo units, and 0.58 for duration of labor in phase 2. Conflict regarding the acceptance of pregnancy also correlated significantly with the newborns' 5 minute Apgar scores. Anxiety in labor and plasma epinephrine were significantly correlated with the fetal heart rate pattern during phase 2 of active labor. The fetal heart rate pattern was significantly correlated with newborns' Apgar scores at 1 and 5 minutes. The results of this study support the following hypotheses: conflicts in pregnancy are predictive of maternal anxiety and stress-related biochemical factors, and these variables are related to prolonged labor and to fetal-newborn depression.

Plasma estriol in the evaluation of third-trimester gestational age.

This study attempts to confirm previous reports of a clinically useful serum unconjugated estriol surge at 36 weeks' gestation. Although an apparently physiologic estriol surge occurred at 36 +/- 2.1 weeks in 25 of 32 patients, clinical reality makes weekly plasma sampling difficult. In individual cases, use of the "surge point" predicted gestational age within a 4-week range with only 66% accuracy, and potentially serious errors in dating occurred. Other biochemical (lecithin:sphingomyelin, phosphatidylglycerol) and sonographic methods are superior in resolving problems with dating gestational age in the third trimester.

The role of sympathetic activity in normal renin essential hypertension.

Understanding the connection between sympathetic activity and essential hypertension is still rudimentary. We studied interrelationships of plasma catecholamines, plasma renin activity (PRA), aldosterone, sodium intake, and therapeutic response of 20 normal renin hypertensives. Based on plasma norepinephrine (NE), this population fell into two distinct subsets. The 11 patients in the "normal" NE subset had a basal NE of 257 +/- 49 pg/ml (vs 250 +/- 62 pg/ml in normotensives), while nine patients in the "high" range NE group averaged 522 +/- 125 pg/ml. Both NE subsets showed significant correlation between mean arterial pressure (MAP) and NE. Only the "normal" NE subset showed significant correlation between MAP and PRA, and MAP and aldosterone. Correlations between changes in Na+ excretion and NE, PRA, and aldosterone were all negative and statistically significant. Blood pressure was controlled in eight of 11 "normal" NE patients but only in one of nine "high" NE patients by restriction of Na+ intake and/or use of a diuretic.

Diurnal variations in unconjugated and total plasma estriol levels in late normal pregnancy.

Diurnal variations in plasma unconjugated and total estriol were assessed in 11 third-trimester subjects with uncomplicated pregnancies. Commercially available 125I-labeled radioimmunoassay kits were used. Total plasma estriols reach a nadir during the hours of sleep (400 and 700 hours) which exceeds the episodic fluctuations seen from day to day or during a given 90-minute period. Plasma unconjugated estriol fluctuations over 24 hours did not significantly exceed our previously reported episodic fluctuation of 15.6 +/- 8.2%. The data are interpreted as showing no circadian rhythm, but reflecting, in the case of total plasma estriols, an effect of improved renal clearance during hours of rest. Plasma unconjugated estriol emerges as the test of choice in the monitoring of high-risk pregnancies.