Comparison between the CEDIA and EMIT II immunoassays for the determination of benzodiazepines.

We evaluated a new, qualitative immunoassay for benzodiazepines in urine using CEDIA technology on the Hitachi 747 and compared its performance to an immunoassay using EMIT II methodology on the same instrument. A total of 500 urine samples received for routine drug screen analysis were prospectively examined for benzodiazepines by both methods. Samples producing positive results by either immunoassay method were analyzed by gas chromatography-mass spectrometry (GC-MS). Available medical records were reviewed for patients whose samples produced discrepant immunoassay results or that were positive in both immunoassays but negative by GC-MS. Samples that produced negative results in both immunoassays were not subjected to GC-MS analysis. Therefore, identification of an immunoassay result as a false negative only occurred when the sample produced a positive value in only one of the two immunoassays and was confirmed as positive by either GC-MS or medical record review. Following initial immunoassay screening and confirmation by GC-MS, a medical record review and reanalysis of GC-MS data was performed. After this in-depth analysis of the data, the CEDIA method produced 60 true-positives, 7 false positives and no false negatives. The EMIT II method produced 47 true positives, 1 fase positive and 13 false negatives. These differences appear to be due to the CEDIA assay being more sensitive for detection of lorazepam.

Septal extension grafts: a method of controlling tip projection shape.

Failure to control the projection, shape, and rotation of the nasal tip is a common occurrence among patients with weak lower lateral cartilages. These patients' noses are characterized by a weak midvault, a plunging tip with "Polly beak," and drawn-up alae. The purpose of our study was to identify methods for controlling the position and shape of the nasal tip in these high-risk patients. Twenty patients at risk of losing nasal tip projection were retrospectively identified, and measurements made from their preoperative and postoperative photographs were compared. Loss of tip projection occurred in all but one patient whose columella strut was fixed to the caudal septum. Prompted by these failures, we studied the relationship between the dorsum and tip in cadaveric specimens with and without a supratip break. From our observations, a structural extension of the septum-an anterior septal extension graft-was developed to predictably control this relationship. The clinical application of septal extension grafts in open rhinoplasty was subsequently evaluated in 20 patients who were deemed to be at risk of losing tip projection. Postoperative photographic analysis showed nasal tip projection to be maintained or increased in all but one patient with the use of septal extension grafts. A stable caudal septum is essential to the success of the technique.

Effects of the Transcendental Meditation program on adaptive mechanisms: changes in hormone levels and responses to stress after 4 months of practice.

Stress has been implicated in both somatic and mental disorders. The mechanisms by which stress leads to poor health are largely unknown. However, studies in animals suggest that chronic stress causes high basal cortisol and low cortisol response to acute stressors and that such changes may contribute to disease. Previous studies of the Transcendental Meditation (TM) technique as a possible means of countering effects of stress have reported altered levels of several hormones both during the practice and longitudinally after regular practice of this technique. In this prospective, random assignment study, changes in baseline levels and acute responses to laboratory stressors were examined for four hormones-cortisol, growth hormone, thyroid-stimulating hormone and testosterone-before and after 4 months of either the TM technique or a stress education control condition. At pre- and post-test, blood was withdrawn continuously through an indwelling catheter, and plasma or serum samples were frozen for later analysis by radioimmunoassay. The results showed significantly different changes for the two groups, or trends toward significance, for each hormone over the 4 months. In the TM group, but not in the controls, basal cortisol level and average cortisol across the stress session decreased from pre- to post-test. Cortisol responsiveness to stressors, however, increased in the TM group compared to controls. The baselines and/or stress responsiveness for TSH and GH changed in opposite directions for the groups, as did the testosterone baseline. Overall, the cortisol and testosterone results appear to support previous data suggesting that repeated practice of the TM technique reverses effects of chronic stress significant for health. The observed group difference in the change of GH regulation may derive from the cortisol differences, while the TSH results are not related easily to earlier findings on the effects of chronic stress.

Electrophysiological correlates of higher states of consciousness during sleep in long-term practitioners of the Transcendental Meditation program.

Standard ambulatory night sleep electroencephalograph (EEG) of 11 long-term practitioners of the Transcendental Meditation (TM) program reporting "higher states of consciousness" during sleep (the experimental group) was compared to that of nine short-term practitioners and 11 non-practitioners. EEG tracings during stages 3 and 4 sleep showed the experimental group to have: 1) theta-alpha activity simultaneously with delta activity and 2) decreased chin electromyograph (EMG) during deep sleep (p = 0.002) compared to short-term practitioners. Spectral analysis fast Fourier transform (FFT) data of the first three cycles showed that: 3) the experimental subjects had significantly greater theta 2 (6-8 Hz)-alpha 1 (8-10 Hz) relative power during stages 3 and 4 than the combined control groups [t(30) = 5.5, p = 0.0000008] with no difference in time in delta; 4) there was a graded difference across groups during stages 3 and 4 in theta 2-alpha 1 power, with experimentals having greater power than short-term practitioners, who in turn had greater power than non-practitioners [t(30) = 5.08, p = 0.00002]; and 5) experimentals also had increased rapid eye movement (REM) density during REM periods compared to short-term practitioners (p = 0.04). Previous studies have found increased theta-alpha EEG activity during reported periods of "transcendental consciousness" during the TM technique. In the Vedic tradition, as described by Maharishi Mahesh Yogi, transcendental consciousness is the first of a sequence of higher states. The maintenance of transcendental consciousness along with deep sleep is said to be a distinctive criterion of further, stabilized higher states of consciousness. The findings of this study are interpreted as physiological support for this model.

A controlled study of the effects of the Transcendental Meditation program on cardiovascular reactivity and ambulatory blood pressure.

Cardiovascular responses to stress reactivity has been proposed as a risk factor for hypertension. In this study, we evaluated the effects of stress reduction on both laboratory cardiovascular reactivity and ambulatory blood pressure in real life on 39 normotensive male subjects who were pretested for ambulatory blood pressure and cardiovascular reactivity to stress using a battery of laboratory stressors. Thereafter, subjects were randomly assigned to practice either the Transcendental Meditation (TM) technique or a cognitive-based stress education control (SEC) for four months. After 4 months, there was no change in cardiovascular response to stressors between the TM and control groups. However, the subjects regularly practicing TM demonstrated a significant reduction of 9 mm Hg (p < .04) in average ambulatory DBP compared to controls. Since ambulatory BP monitoring has been shown to be a better predictor of cardiovascular complications of hypertension than clinic BP, this finding may have important implications for primary prevention of CVD in normotensive subjects.

Anger expression correlates with platelet aggregation.

Potential relationships between increased platelet aggregability and such psychological characteristics as hostility and anger were investigated as part of a larger intervention study investigating the potential efficacy of stress-reduction treatments. Participants performed 6-minute mental arithmetic tests under time pressure. Blood was sampled during the first minute of the task and whole blood platelet aggregation was measured in an aggregometer, using collagen and ADP. To assess anger and hostility, the authors used Spielberger's State-Trait Anger and Anger Expression scales together with the Cook-Medley Hostility Scale. The authors found positive correlations between collagen-induced platelet aggregation and outwardly expressed anger, as measured by the Anger Expression Scale. The findings suggested that modes of anger expression may be associated with increased platelet aggregation. If confirmed by future studies, this finding could provide a mechanism for the putative connection between anger/hostility and coronary heart disease.

Trial of stress reduction for hypertension in older African Americans. II. Sex and risk subgroup analysis.

Our objective was to test the short-term efficacy and feasibility of two stress-reduction approaches for the treatment of hypertension in older African Americans, focusing on subgroup analysis by sex and by high and low risk on six measures of hypertension risk: psychosocial stress, obesity, alcohol use, physical inactivity, dietary sodium-potassium ratio, and a composite measure. The study involved a follow-up subgroup analysis of a 3-month randomized, controlled, single-blind trial conducted in a primary care, inner-city health center. Subjects were 127 African American men and women, aged 55 to 85 years, with diastolic pressure of 90 to 104 mm Hg and systolic pressure less than or equal to 179 mm Hg. Of these, 16 did not complete follow-up blood pressure measurements. Mental and physical stress-reduction approaches-the Transcendental Meditation technique and progressive muscle relaxation, respectively-were compared with a life-style modification education control and with each other. Both systolic and diastolic pressures changed from baseline to follow-up for both sexes and for high and low risk level (defined by median split) on the six measures of hypertension risk. Compared with education control subjects, women practicing the Transcendental Meditation technique showed adjusted declines in systolic (10.4 mm Hg, P < .01) and diastolic (5.9 mm Hg, P < .01) pressures. Men in this treatment group also declined in both systolic (12.7 mm Hg, P < .01) and diastolic (8.1 mm Hg, P < .001) pressures compared with control subjects. Women practicing muscle relaxation did not show a significant decrease compared with control subjects, and men declined significantly in diastolic pressure only (6.2 mm Hg, P < .01). For the measure of psychosocial stress, both the high and low risk subgroups using the Transcendental Meditation technique declined in systolic (high risk, P = .0003; low, P = .06) and diastolic (high risk, P = .001; low, P = .008) pressures compared with control subjects, whereas for muscle relaxation, blood pressure dropped significantly only in the high risk subgroup and only for systolic pressure (P = .03) compared with control subjects. For each of the other five risk measures, Transcendental Meditation subjects in both the high and low risk groups declined significantly in systolic and diastolic pressures compared with control subjects. Effects of stress reduction on blood pressure were found to generalize to both sexes and diverse risk factor subgroups and were significantly greater in the Transcendental Meditation treatment group. These effects (along with high compliance) even in individuals with multiple risk factors for hypertension clearly warrant longer-term investigation in this and other populations.

Renal artery aneurysm: a report of 28 cases.

Renal artery aneurysms are being increasingly encountered due to the wider use of angiography. From 1972 to 1992, 28 patients with renal artery aneurysm were identified in the present study, including 18 women and 10 men, with a mean age of 58 years. The aneurysms were discovered incidentally in 39% of patients during evaluation for hypertension in 39%, and during investigation of abdominal pain in 22%. Only 7% of patients had symptoms directly attributable to the aneurysm. Aneurysm size varied from 0.5cm to 8cm in diameter, with a mean of 2.1 cm. The main renal artery was involved in 52% of cases, and primary branches in 44%; the remainder were intraparenchymal. There was a slight right-sided predominance in this series. The etiology of the aneurysms included atherosclerosis (75%), fibromuscular disease (21%), and Ehlers-Danlos syndrome (4%). Surgical therapy was undertaken in 10 patients (36%). Procedures performed included aortorenal bypass in four patients, aneurysm excision and renal artery repair in three, partial nephrectomy in one, and total nephrectomy in two. Although the natural history of renal artery macroaneurysms is not known with certainty, potential complications include embolization and rupture. The authors' indications for surgery include: (a) symptomatic or enlarging aneurysms; (b) renal embolization; (c) aneurysms in pregnant females or those considering pregnancy; (d) renovascular hypertension; (e) aneurysms> 2.5cm. Most symptom-free aneurysm s<2.5 cm in diameter can be safely treated expectantly.

The impact of the transcendental meditation program on government payments to physicians in Quebec.

PURPOSE: This study evaluated whether governmental medical payments in Quebec were affected by the Transcendental Meditation (TM) technique. DESIGN: This retrospective study used a pre- and postintervention design in which government payments for physicians' services were reviewed for 3 years before and up to 7 years after subjects started the technique. Payment data were adjusted for aging and year-specific variation (including inflation) using normative data. No separate control group was used; thus it is impossible to determine whether the changes were caused by the TM program or some other factor. SUBJECTS: A volunteer group of 677 provincial health insurance enrollees was evaluated. The subjects had chosen to practice the TM technique before they were selected to enter the study. The subjects (348 men, 329 women) had diverse occupations. Their average age was 38 years and ranged from 18 to 71 years at the start of the TM program. INTERVENTION: The TM technique of Maharishi Mahesh Yogi is a standardized procedure practiced for 15 to 20 minutes twice daily while sitting comfortably with eyes closed. SETTING: Province of Quebec, Canada. RESULTS: During the 3 years before starting the TM program, the adjusted payments to physicians for treating the subjects did not change significantly. After beginning TM practice, subjects' adjusted expenses declined significantly. The several methods used to assess the rate of decline showed estimates ranging from 5% to 7% annually. CONCLUSIONS: The results suggests that the TM technique reduces government payments to physicians. However, because of the sampling method used, the generalizability of these results to wider populations could not be evaluated.

Stress reduction and preventing hypertension: preliminary support for a psychoneuroendocrine mechanism.

Our objective was to identify endocrine-related mechanisms capable of mediating preventive effects of stress reduction in hypertensive heart disease. Since beneficial effects of stress reduction accrue over time, this cross-sectional, descriptive study sought differences between healthy students not practicing a systematic technique for reducing stress (the average stress, or AS, group, n = 33) and a similar group who for 8.5 years had practiced the Transcendental Meditation (TM) technique, used widely to reduce stress (the low stress, or LS, group, n = 22). The two groups of students, matched for age and area of study, performed timed collections of urine that included (separately) the entire waking and sleeping portions of 1 day. They also completed the Profile of Mood States and the State-Trait Anxiety Inventory, self-report instruments sensitive to subjective level of stress. Urine samples were analyzed for adrenocortical steroids by radioimmunoassay, for Na+, K+, Mg2+, Ca2+, and Zn2+ by atomic absorption spectrometry, and for neurotransmitter metabolites by reverse-phase, high-performance, liquid chromatography, and spectrophotometry. The two groups differed significantly on most measures. Specifically, the LS group was lower in cortisol and aldosterone and higher in dehydroepiandrosterone sulfate (DS) and the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA). Excretion of sodium, calcium, zinc, and the norepinephrine metabolite, vanillylmandelic acid (VMA), was also lower in this group, as were Na+/K+ ratio, mood disturbance, and anxiety. In women practicing TM, cortisol correlated inversely and DS directly with number of months of TM practice. The results identify improvements in mood state, adrenocortical activity, and kidney function as probable factors in the preventive and treatment effects of stress reduction. Because suboptimal levels of these parameters result from chronic, subjective stress, the findings add mechanistic support to the contention that hypertensive heart disease is avoidable, even in modern industrialized societies.

Stress, steroids, and "ojas": neuroendocrine mechanisms and current promise of ancient approaches to disease prevention.

Recent research on causes of disease and aging has increasingly supported the importance of stress. One theory of the relationship between stress and disease is based on the concept of homeostasis, a term coined by Cannon over 50 years ago to signify those states and mechanisms responsible for the "staying power of the body". Bernard, Cannon, Selye and other leading researchers held that full, normal function of the self-regulating or homeostatic power of the body maintains the balanced, integrated condition we recognize as health. Failures in this capacity, such as those produced by frequent stressful experiences, can result in disease or death. Theories of health and disease surprisingly similar to this have existed since ancient times, and in widely different cultures. This review discusses both the fundamental elements of these theories and the current neuroendocrine research supporting their validity and immediate relevance. The connections between ancient and modern knowledge described herein were made possible largely by the work of Maharishi Mahesh Yogi, a scholar and teacher of the ancient vedic tradition of India. A key part of Ayurveda that has been obscure to modern science is the substance "ojas", which the classical texts say maintains balance of the physiology. In this article, specific steroids or steroid classes are proposed as likely candidates for both the "ordinary" and the "superior" types of ojas described in Ayurveda. Current evidence for the functions of these steroids, as well as their role in stress, disease and the maintenance of health, is reviewed. The knowledge of Ayurveda, as recently brought to light by Maharishi, includes methods for recovering and maintaining optimal function of steroidal systems. Such effects may help mediate the improvements in health and increased longevity attributed to Ayurveda and other ancient methods.

Evaluation of a new colorimetric assay for serum lithium.

Using patient samples (n = 175) collected in our clinical chemistry laboratory, we have undertaken an analysis of a new colorimetric dry slide-based serum lithium (Li+) assay from Eastman Kodak for its Ektachem instrumentation series. Analyzer imprecision was acceptable, and good correlation was seen between the Ektachem assay and an ion-selective electrode (ISE)-based assay currently in use in our laboratory (r = 0.99). At all concentrations tested, potassium (K+), triglycerides, or bilirubin did not detectably interfere with the Ektachem determination of Li+. At concentrations within the reference range (135-145 mmol/L), sodium (Na+) did not affect the Ektachem Li+ determination. A slight Na(+)-dependent positive bias in the Li+ determination was evident at 157 mmol/L, but became clinically significant (> or = 0.2 mmol/L) only at physiologically extreme concentrations (> 188 mmol/L) of Na+. Very high concentrations (> 325 mg/dl) of hemoglobin also were found to cause a clinically significant positive bias. We conclude that the determination of Li+ by the Kodak Ektachem is precise, accurate, and adequately free from bias due to common interferents or other monovalent cations, and, therefore, is an acceptable alternative to currently available methods for the monitoring of serum LI+.

Effectiveness of the Transcendental Meditation program in preventing and treating substance misuse: a review.

This article reviews 24 studies on the benefits of Transcendental Meditation (TM) in treating and preventing misuse of chemical substances. Studies cover noninstitutionalized users, participants in treatment programs, and prisoners with histories of heavy use. All the studies showed positive effects of the TM program. Some of the survey-type studies were unable to exclude the possibility of self-selection or responder biases. However, longitudinal, random-assignment studies with objective measures also showed positive results. Taken together, these and other studies indicate the program simultaneously addresses several factors underlying chemical dependence, providing not only immediate relief from distress but also long-range improvements in well-being, self-esteem, personal empowerment, and other areas of psychophysiological health.

Beta-adrenergic receptor sensitivity in subjects practicing transcendental meditation.

Several studies suggest that behavioral techniques such as meditation and relaxation may be associated with reduced end organ adrenergic receptor sensitivity. Thus far the evidence supporting this hypothesis has been indirect. We present preliminary findings showing reduced beta-adrenergic receptor sensitivity in a group of subjects practicing Transcendental Meditation. The meditation group (N = 10), compared to controls (N = 10), had a lower percentage of functional lymphocyte beta-adrenergic receptors (p = 0.009), but showed no difference in total receptor number or plasma catecholamines. There were no differences between the groups in Type A behavior, the Type A components, exercise, or family history of hypertension. The results provide some support for studies postulating that meditation is associated with reduced sympathetic adrenergic receptor sensitivity, and provide encouragement for the efficacy of receptor measurement in psychophysiology research.

The theophylline method of the Abbott "Vision" analyzer evaluated.

We evaluated the analytical performance of the Abbott "Vision" analyzer for theophylline measurement. The within-day precision (CV) was 1.8% and 3.1% at theophylline concentrations of 15.2 and 25.2 mg/L, respectively; between-day precision was 3.5% and 4.8% at 14.9 and 24.4 mg/L, respectively. Bilirubin (143 mg/L) and triglyceride (7.4 g/L) did not interfere, but hemoglobin caused lower values for apparent theophylline, the magnitude of the decrease being proportional to the hemoglobin concentration. At the cutoff concentration of 1 g/L programmed into the instrument by the manufacturer, hemoglobin reduced the theophylline value by less than 10%. Results by the Vision method (y) compared well with those by the "TDX" procedure (x): r = 0.98, y = 0.978x - 0.270 mg/L. The Vision method gave comparable theophylline values for serum, plasma, and whole-blood samples. We also validated analytically and clinically that capillary blood samples collected by finger stick can be used interchangeably with blood samples collected by venipuncture for monitoring theophylline therapy.

The noradrenergic system in cultured aggregates of fetal rat brain cells: morphology of the aggregates and pharmacological indices of noradrenergic neurons.

Spherical aggregates formed rapidly in culture by re-aggregation of trypsin-dissociated brain cells from the 17-day-old fetal rat. Over about 10 days in initially random distribution of cells evolved into a 3-layered arrangement; cells with characteristics of neurons were found largely in the intermediate layer. The survival of neuronal and glial cell types was evaluated histologically and verified by electron microscopy, which revealed synaptic and myelin structures that rapidly increased in number after 18 days in culture. Levels of norepinephrine (NE) and dopamine (DA) reached peaks of 9.5 and 4.4 ng/mg protein, respectively, at culture day 21. Uptake of [3H]NE paralleled these amine levels and was blocked by desipramine or pretreatment with either reserpine or 6-OH-DA. Autoradiographs of aggregates labeled with [3H]NE showed a high density of silver grains over cells, apparently neurons, with branching processes traced for 120 micrometer. Previously accumulated [3H]NE was released under depolarizing conditions (high [K+] or vertridine) only in the presence of Ca2+. Release was induced to a lesser extent by kainic greater than glutamic acid. Thus, such aggregates appear to contain catecholaminergic neurons capable of synthesis, uptake and release of NE. The time course of development of these functions supports suggestions that aggregate preparations might be useful in studying neurochemical or morphological aspects of brain development and function in vitro.