Panic and panic disorder in the United States

OBJECTIVES: Shift work and rapid travel across several time zones leads to desynchronization of internal circadian rhythms from the external environment and from each other with consequent problems of behaviour, physiology and performance. Field studies of travellers and shift workers are expensive and difficult to control. This investigation concerns the simulation of such rhythm disturbance in a laboratory environment. The main objectives are to assess the ability of controlled exposure to moderately bright light and darkness/sleep to delay circadian rhythms in volunteers without environmental isolation and, secondly, to evaluate the use of different indices of melatonin (MT) secretion together with self-rated alertness as marker rhythms. PATIENTS: Six normal volunteers aged 22-26 years (mean +/- SD 24.3 +/- 1.4). DESIGN: Subjects were exposed to the following periods of moderately bright light (1200 lux) on three consecutive days in early December 1991: Day (D)1: 2000-0200 h, D2: 2200-0400 h and D3: 2400-0600 h. Each period was followed by 8 hours of darkness (< 1 lux). Hourly blood, sequential 4-hourly urine (8-hourly when asleep) and hourly saliva (except when asleep) samples were taken throughout a 24-hour period on D0 (baseline), D4 (1 day post-light treatment) and D7 (4 days post-light treatment). During waking hours, subjective alertness was rated every 2 hours on a visual analogue scale. MEASUREMENTS: MT was measured in plasma and saliva, and its metabolite, 6-sulphatoxymelatonin (aMT6s), was measured in urine. MT, aMT6s and alertness scores were analysed by ANOVA and a cosinor analysis program. RESULTS: A delay shift was present in the aMT6s, plasma MT and salivary MT rhythms (degree of shift: 2.67 +/- 0.3 h (P < 0.001, n = 5); 2.35 +/- 0.29 h (P < 0.001, n = 6); and 1.97 +/- 0.32 h (P < 0.01, n = 6), mean +/- SEM, respectively) 1 day post-light treatment compared to baseline. Adaptation to the initial phase position was apparent by the 4th post-treatment day. Significant correlations were obtained between plasma MT onset (degree of shift: 3.12 +/- 0.74 h (P < 0.001, n = 6, mean +/- SEM)) and the acrophases (calculated peak times) of plasma MT (P < 0.001), salivary MT (P < 0.05) and urinary aMT6s (P < 0.01). A significant phase delay in the alertness rhythm was also evident 1 day post-treatment (3.08 +/- 0.67 h (P < 0.01, n = 6, mean +/- SEM)) with adaptation by the 2nd post-treatment day. CONCLUSIONS: This study suggests that these methods of determining MT secretion are comparable and give reliable assessments of the MT circadian phase position even after a phase-shift. Significant phase-shifts of similar magnitude can be induced in both MT and alertness rhythms using moderate intensity bright light at night.     

Observed and self-reported seat belt wearing as related to prior traffic accidents and convictions

During the summer of 1987, 10,000 color-coded mailback questionnaires that identified belted and unbelted North Carolina drivers were handed out at the 72 sites that constitute the probability sample for determining the statewide belt use rate in North Carolina. By obtaining identifying information to determine the winner of a $500 prize from among the 5,074 respondents, police-reported traffic accident and conviction records from the North Carolina driver history file were linked to the belted and unbelted respondents. Analyses found that drivers who had been observed not wearing seat belts had 35% more accidents and 69% more convictions than did belted drivers in the previous four-year period. Similar findings were obtained from self-reported belt use.     

Suppression of human bladder cancer growth by increased expression of C-CAM1 gene in an orthotopic model

Recently, we demonstrated that an immunoglobulin-like cell adhesion molecule, C-CAM, acts as a tumor suppressor in prostate cancer. It is known that C-CAM is expressed in many epithelial cell types. In this study, we tested the possibility that C-CAM may also suppress bladder cancer progression. We used an orthotopic tumor model, which provides a relevant organ condition for examining the interaction between primary tumor cells and their microenvironment; this interaction has a critical impact on the behavior of carcinoma. We constructed a recombinant adenovirus expressing C-CAM1 (an isoform of C-CAM) and infected the 253J B-V cell line, a tumorigenic human bladder carcinoma subline. In vitro, C-CAM1 protein was detected in C-CAM1 adenovirus-infected cells but not in antisense control virus-infected cells, and the levels of expression showed dose dependency. When these cells were injected orthotopically in nude mice, we found that the increased expression of C-CAM1 in the 253J B-V cells repressed the growth of 253J B-V-induced tumors. Taken together, these data indicate that C-CAM1 is a potent tumor suppressor in human bladder cancer.     

Ventricular fibrillation-induced intracellular Ca2+ overload causes failed electrical defibrillation and post-shock reinitiation of fibrillation

Despite high efficacy, electrical defibrillation shocks can fail or ventricular fibrillation (VF) is reinitiated after the application of the initial shock. The goal of this study was to determine whether [Ca2+]i overload, induced by VF itself, can cause failed electrical defibrillation and post-shock reinitiation of VF. For this purpose, we simultaneously measured [Ca2+]i transients (assessed by indo-1 fluorescence) and defibrillation energies (assessed by a modified implantable cardioverter defibrillator) in intact perfused rat hearts during pacing-induced sustained VF (10 min) in the absence of ischemia. We found that increasing [Ca2+]i during VF (by increasing [Ca2+]o from 3 to 6 mM) increased the defibrillation threshold (DFT) from 1.9 +/- 0.6 to 3.5 +/- 0.5 J/g (P<0.05) and also increased the total defibrillation energy (TDE) required for stabilization of sinus rhythm from 15.6 +/- 7.7 to 48.6 +/- 7.42 J/g (P<0.05). In addition, both DFT and TDE correlated linearly with [Ca2+]i (r=0.69 and 0.83, P<0.05). Furthermore, shortening the duration of VF from 10 to 1.5 min tended to limit [Ca2+]i overload and decreased TDE. Finally, all successful defibrillation shocks led to a sudden reduction of VF-induced [Ca2+]i overload (-115 +/- 3%). In contrast, failed shocks did not alter [Ca2+]i. Incomplete reduction of [Ca2+]i overload after initially successful shocks were often followed by synchronized spontaneous [Ca2+]i oscillations and subsequent reinitiation of VF. In conclusion, the present study showed for the first time that VF-induced [Ca2+]i overload can cause failed electrical defibrillation and post-shock reinitiation of VF. Because VF inevitably causes [Ca2+]i overload, this finding might be a crucial mechanism of failed defibrillation and spontaneous reinitiation of VF.     

Regulation of the NMDA component of EPSPs by different components of postsynaptic GABAergic inhibition: computer simulation analysis in piriform cortex

Regulation of the NMDA component of EPSPs by different components of postsynaptic GABAergic inhibition: computer simulation analysis in piriform cortex. J. Neurophysiol. 78: 2546-2559, 1997. Physiological analysis in the companion paper demonstrated that gamma-aminobutyric acid-A (GABAA)-mediated inhibition in piriform cortex is generated by circuits that are largely independent in apical dendritic and somatic regions of pyramidal cells and that GABAA-mediated inhibitory postsynaptic currents (IPSCs) in distal dendrites have a slower time course than those in the somatic region. This study used modeling methods to explore these characteristics of GABAA-mediated inhibition with respect to regulation of the N-methyl--aspartate (NMDA) component of excitatory postsynaptic potentials. Such regulation is relevant to understanding NMDA-dependent long-term potentiation (LTP) and the integration of repetitive synaptic inputs that can activate the NMDA component as well as pathological processes that can be activated by overexpression of the NMDA component. A working hypothesis was that the independence and differing properties of IPSCs in apical dendritic and somatic regions provide a means whereby the NMDA component and other dendritic processes can be controlled by way of GABAergic tone without substantially altering system excitability. The analysis was performed on a branched compartmental model of a pyramidal cell in piriform cortex constructed with physiological and anatomic data derived by whole cell patch recording. Simulations with the model revealed that NMDA expression is more effectively blocked by the slow GABAA component than the fast. Because the slow component is present in greater proportion in apical dendritic than somatic regions, this characteristic would increase the capacity of dendritic IPSCs to regulate NMDA-mediated processes. The simulations further revealed that somatic-region GABAergic inhibition can regulate the generation of action potentials with little effect on the NMDA component generated by afferent fibers in apical dendrites. As a result, if expression of the NMDA component or other dendritic processes were enabled by selective block of dendritic inhibition, for example, by centrifugal fiber systems that may regulate learning and memory, the somatic-region IPSC could preserve system stability through feedback regulation of firing without counteracting the effect of the dendritic-region block. Simulations with paired inputs revealed that the dendritic GABAA-mediated IPSC can regulate the extent to which a strong excitatory input facilitates the NMDA component of a concurrent weak input, providing a possible mechanism for control of "associative LTP" that has been demonstrated in this system. Postsynaptic GABAB-mediated inhibition had less effect on the NMDA component than either the fast or slow GABAA components. Depolarization from a concomitant alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) component also was found to have comparatively little effect on current through the NMDA channel because of its brief time course.     

Wide-area network connecting a hospital drug informatics center with a university

Bone age maturation in 116 untreated patients with Turner's syndrome was evaluated in a cross-sectional and longitudinal analysis. A total of 265 radiographs were rated using the TW2-RUS method on the computer-assisted skeletal age score (CASAS) system. Bone age was found to be retarded from the chronological age of 3 to 6y. Between the ages of 7 and 12 y bone age almost equalled chronological age and progressed normally at a rate of 1 y y(-1). Bone maturation slowed down thereafter and epiphyseal closure was not reached before the age of 17 y. Reference data are presented on bone age and a bone age maturation curve for untreated patients with Turner's syndrome to be used in clinical practice. In the assessment of bone age and bone age velocity in Turner's syndrome the CASAS system produced reliable and valid results. The absolute difference between repeated bone age ratings was 0.26 "y" (median) with a range of 0.00-0.56 "y". Future studies evaluating the effect of growth-promoting treatment in Turner's syndrome should use a computerized method for the determination of bone age.     

Survival in neonatal biventricular repair of left-sided cardiac obstructive lesions associated with hypoplastic left ventricle

Patients with left ventricular hypoplasia and left-sided heart obstructive lesions other than critical aortic stenosis may be inappropriately subjected to single ventricular repair because their assessment is based on faulty qualitative evaluations or on quantitative methods developed for critical aortic stenosis. Patients with left ventricular hypoplasia and left-sided heart obstructions other than critical aortic stenosis successfully underwent biventricular repair despite "failing" to pass established criteria for critical aortic stenosis.