Rats bred for ethanol sensitivity: Impairment of swimming by ethanol and pentobarbital

Rats selectively bred for disparate degrees of ethanol-induced depression of spontaneous locomotor activity (most affected = MA; least affected = LA) were trained on a swim task. Undrugged rats of the MA line swam significantly faster than rats of the LA line. Ethanol, 0.0–2.25 g/kg i.p., produced dose-dependent increases in swim time in rats of the 13th generation (F13). Averaged over trials, these increases were greater in LA than in MA rats and greater in males than in females, but there was no sex difference in peak impairment. Increases in swim time were uncorrelated with predrug performance. These findings were confirmed in younger F17 rats receiving 1.75 g EtOH/kg i.p. Although the lines differed in ethanol-induced impairment, F17 males of the two lines were not differentially impaired by pentobarbital (12.5–22.5 mg/kg, i.p.). The existence of task-dependent line differences in ethanol sensitivity emphasizes the nonunitary nature of ethanol-induced behavioral depression.     

Effect of age and pregnancy on the antibody and cell-mediated immune responses of horses to equine herpesvirus 1.

The cell-mediated immune response and antibody response of horses of varying ages and of pregnant horses to equine herpesvirus 1 antigen were examined. Six to eight month old horses showed either no increase or slight increases in anti-equine herpesvirus 1 serum neutralizing antibody following vaccination and revaccination with a modified live equine herpesvirus 1 vaccine. However, these same horses showed a marked increase in the cell-mediated immune response to equine herpesvirus 1 as measured by the lymphocyte transformation test. Eighteen to 21 month old horses showed four to 64-fold increases in anti-equine herpesvirus 1 serum neutralizing antibody titer following vaccination, but the cell-mediated immune response to equine herpesvirus 1 was low or absent. Only after revaccination did they show an increased cell-mediated immune response to equine herpesvirus 1. The cell-mediated immune response of mares in the latter stages of pregnancy to equine herpesivurs 1 was suppressed although antibody titers increased as much as 16-fold following exposure to virulent equine herpesvirus 1.     

Relation between prepublication release of clinical trial results and the practice of carotid endarterectomy

Context  Little is known about how clinical practice is affected by disseminating results of clinical trials prior to publication in peer-reviewed journals. Objective  To determine whether prepublication release of carotid endarterectomy (CEA) trial results via National Institutes of Health Clinical Alerts was associated with prompt changes in patient care that were consistent with the new medical evidence. Design, Setting, and Patients  Longitudinal data series analysis using acute care hospital discharge data from the Healthcare Cost and Utilization Project for patients who had CEA performed in acute care hospitals in 7 states (New York, California, Pennsylvania, Florida, Colorado, Illinois, and Wisconsin). The trials were the North American Symptomatic Carotid Endarterectomy Trial (NASCET clinical alert released February 1991) and the Asymptomatic Carotid Atherosclerosis Study (ACAS clinical alert released September 1994). Main Outcome Measure  Carotid endarterectomy rate during each month from 1989 (2 years before the NASCET clinical alert) to 1996 (2 years after the ACAS clinical alert), adjusted for age and sex. Because both trials were limited to patients 80 years or younger in hospitals with low mortality, we also stratified CEA rates by patient age and hospital mortality rate. Results  From 1989 through 1996, 272,849 CEAs were performed in the acute care hospitals in these 7 states, with the annual number increasing from 22,300 to 51,495. After the NASCET clinical alert, the adjusted CEA rate increased 3.4% per month (95% confidence interval [CI], 1.6%-5.3%) during the following 6 months and then increased 0.5% per month (95% CI, 0.2%-0.8%; P<.04) after journal publication of the NASCET study. After the ACAS clinical alert, the CEA rate increased 7.3% per month (95% CI, 6.0%-8.5%) during the following 7 months and then decreased by 0.44% per month (95% CI, -0.86% to -0.0002%; P<.04) after journal publication of the ACAS study. After the ACAS clinical alert, the CEA rate increased more in patients aged 80 years or older than in younger patients; whereas, after journal publication of ACAS, the CEA rate decreased more rapidly in the older population. The overall proportion of CEAs performed in low-mortality hospitals did not change substantially after release of the clinical alerts or after journal publication. Conclusion  In this study, prepublication dissemination of CEA trial results with clinical alerts was associated with prompt and substantial changes in medical practice, but the observed changes suggest that the results were extrapolated to patients and settings not directly supported by the trials.      

Rhythmic midbrain-evoked vocalization is inhibited by vasoactive intestinal polypeptide in the teleost Porichthys notatus

Vasoactive intestinal polypeptide (VIP) is distributed in vocal midbrain areas of multiple vertebrate taxa, suggesting that VIP may modulate midbrain-evoked vocalization. To test this hypothesis, neurophysiological experiments were conducted in the teleost Porichthys notatus which generates vocalizations in mating and agonistic contexts. Electrical stimulation of the paralemniscal midbrain and local delivery of VIP were conducted in conjunction with occipital nerve recordings that reflect the patterned output of hindbrain vocal circuitry. Consistent with our hypothesis, VIP significantly reduced the duration and number of rhythmic vocal-motor bursts obtained in a dose-dependent manner; vocalization latency was concomitantly increased. These results provide the first evidence for VIP modulation of midbrain vocal function.     

Detecting changes in functional ability in women with premenstrual syndrome

There has been a lack of objective assessment of the disruptive effect that the symptomatology of premenstrual syndrome has on the functional performance of affected women. This study assessed the functional performance of women with premenstrual syndrome at four phases of the menstrual cycle. Twelve women with premenstrual syndrome and nine asymptomatic women were tested on four functional instruments at the menstrual, early follicular, early luteal, and late luteal phases. Two tests of a paper-and-pencil type measured perceptual parameters, and two tests involving manipulation of objects measured manual dexterity. Mean performance on the Crawford Small Parts Dexterity Test--Part II, which tests fine motor function, was better at the late luteal testing, compared to the early follicular testing, in asymptomatic women but was worse in the women with premenstrual syndrome. This difference was statistically significant (p = 0.015). No significant differences between groups in performance changes were observed for the other functional tests. The Crawford Small Parts Dexterity Test-Part II is an objective measure that is potentially valuable in therapeutic trials involving patients with premenstrual syndrome.     

Prophylactic furosemide in severe respiratory distress syndrome: blinded prospective study

To further characterize the place for furosemide in the treatment of newborn infants with respiratory distress syndrome requiring mechanical ventilation, we conducted a blinded, prospective study comparing early prophylactic use (1 mg/kg every 12 hours for four doses beginning at 24 hours of age) with prn use of this drug. Prophylactic administration of furosemide produced no beneficial effect on any measure of pulmonary function compared with use of this drug as needed (prn). However, patients receiving the prophylactic furosemide regimen were found to have more rapid postnatal weight loss, higher pulse rate, and greater sympathomimetic drug requirement during the period of diuretic administration. Patients in the prophylactic group did not demonstrate the moderate expansion in plasma volume between 48 and 96 hours of age seen in the control group. These data suggest that the prophylactic regimen produced an undesirable degree of volume depletion. Further studies should be conducted to develop objective criteria for the selection of the subgroup of patients with respiratory distress syndrome who may benefit from furosemide.