Unique behavioral effects of the NMDA antagonist, CPP, upon injection into the medial pre-frontal cortex of rats

Injection of the specific N-methyl-D-aspartate (NMDA) antagonist, 3(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), into the frontal cortex of rats, induced hyperactivity characterized by unique episodic darting behavior. This behavioral profile contrasts sharply with the ataxia and hyperactivity seen after intracerebroventricular CPP and other NMDA antagonists.     

The effect of chronic hexarelin administration on the pituitary–adrenal axis and prolactin

OBJECTIVE: With the development of growth hormone (GH) releasing agents and their use in human subjects, it is clear that these agents are not specific for GH release. More recent studies in humans have demonstrated acute increases in adrenocorticotrophic hormone (ACTH), cortisol and prolactin (PRL) after boluses of intravenous or subcutaneous GHRPs. The potential adverse effects of repeated episodes of transient hyperprolactinaemia and hypercortisolaemia during long-term therapy with growth hormone releasing peptides (GHRPs) and similar agents have raised concern. We have therefore assessed the impact of chronic hexarelin administration on the pituitary-adrenal axis and serum prolactin levels. DESIGN: Each subject received twice-daily subcutaneous hexarelin therapy (1.5 micrograms/kg body weight) for 16 weeks. The ACTH, cortisol and PRL responses to the morning subcutaneous injection of hexarelin were assessed. Hexarelin was administered at time 0 and blood samples were taken at -10, 0, 10, 20, 30, 40, 50, 60, 90, 120, 170 and 180 min. The ACTH and PRL responses were assessed at baseline and after 16 weeks of therapy. The cortisol response was assessed at baseline, 16 weeks and also 4 weeks after completion of hexarelin therapy. Basal levels of cortisol binding globulin (CBG), 24-h urinary free cortisol (UFC) estimations, thyroid stimulating hormone (TSH) and total thyroxine (TT4) were performed at baseline, weeks 16 and 20. RESULTS: The mean (+/- SEM) area under the cortisol curve (AUCCORT) at baseline, week 16 and week 20 were 1506 (+/- 77) nmol/l/h, 1222 (+/- 92) nmol/l/h and 1586 (+/- 58) nmol/l/h, respectively. There was a significant change in AUCCORT over the study period (P = 0.008). Compared with baseline, AUCCOPRT had decreased significantly (P < 0.05) after 16 weeks of hexarelin therapy. Four weeks after completion of hexarelin therapy, the AUCCORT increased significantly compared with AUCCORT at week 16 (P < 0.01) and was no longer significantly different from baseline values. There were no significant changes in UFC (P = 0.3), basal cortisol measurements (P = 0.19), area under the ACTH curve (AUCACTH) (P = 0.24) or CBG (P = 0.6) over the study period. The mean (+/- SEM) area under the PRL curve (AUCPRL) at the baseline and week 16 were 624 (+/- 82) mU/l/h and 641 (+/- 83) mU/l/h, respectively. There was no significant change in AUCPRL over the study period (P = 0.35). CONCLUSION: The present study demonstrates clearly that in this hexarelin dosage regimen, over-stimulation of the pituitary adrenal axis and prolactin secretion do not occur. In fact the impact of chronic hexarelin therapy on the pituitary-adrenal axis, i.e. decreased AUCCORT, contradict the findings reported after acute hexarelin administration and cannot be explained by changes in CBG. The lack of change in UFC, however, suggests that these changes are unlikely to be of clinical significance although the underlying mechanism requires further study.     

Jimson Weed Extract as a Protective Agent in Severe Organophosphate Toxicity

Treatment of patients following an organophosphate (OP) exposure can deplete a hospital's entire supply of atropine. Given the possibility of multiple severe exposures after a terrorist attack using OP nerve agents, there exists a need for either greater atropine stores or the development of alternative antidotes. Jimson weed (Datura stramonium) contains atropine and other anticholinergic compounds and is common and readily available. It is used recreationally for its central anticholinergic effects and is made easily into an extract by boiling the crushed seeds. The extract has rapid onset of effects and may be useful for treatment of OP poisoning. OBJECTIVES: To determine whether pretreatment with an easily stored and prepared Datura seed extract (DSE) will increase survival following a severe OP poisoning. METHODS: Datura stramonium seeds were collected, crushed, and then heated in water to make a 2-mg/mL atropine solution (100 seeds contain approximately 6 mg of atropine or 0.007 mg/seed). Male rats were randomized to pretreatment with either saline (n = 10) or 7.5 mg/kg DSE (n = 10) given as a single intraperitoneal injection 5 minutes prior to a subcutaneous injection of 25 mg/kg of dichlorvos. The endpoint was time to death recorded by a blinded observer. RESULTS: The Kaplan-Meier estimates of the 24-hour survival rate was 90% (95% CI = 56% to 100%) for the DSE-pretreated group and 10% (95% CI = 0% to 45%) for the control group. The log-rank test revealed a statistically significant longer survival for the Datura-treated animals (p = 0.0002). Median survival time was 22 minutes 30 seconds for the control group and greater than 24 hours for the DSE-pretreated group. CONCLUSIONS: Pretreatment with DSE significantly increases survival following severe dichlorvos exposure.     

Chest radiograph interpretation skills of anesthesiologists

OBJECTIVE: To assess the skills of anesthesiologists in the interpretation of chest radiographs. DESIGN: Randomized evaluation conducted among anesthesiologists and radiologists. SETTING: Postgraduate Assembly of the New York State Society of Anesthesiologists in 1999, and the Department of Radiology, New York University Medical Center. PARTICIPANTS: A total of 61 anesthesiologists (48 attending physicians; 13 residents); control group of 8 radiology residents (all participants volunteered). INTERVENTIONS: After completing a demographic survey, participants were asked to review a series of 10 chest radiographs. A brief clinical scenario accompanied each radiograph. No time limit was set for these interpretations. Measurements and Main Results: The demographic characteristics of the anesthesiology participants included university faculty (46%), private group practitioners (41%), independent practitioners (11%), and 1 participant with an unspecified type of practice. Additional training among the participants included internal medicine (31%), surgery (19%), and pediatrics (3%); 34% did not specify any additional training. Of the participants, 92% were involved in cases requiring general anesthesia; 96% managed patients in the recovery room; and 34% managed patients in the intensive care unit. Of participants, 80% usually order chest radiographs, but only 42% interpret the films themselves. Misdiagnosed radiographs included pneumothorax by 11% of participants, free air under the diaphragm by 41%, bronchial perforation from a nasogastric tube by 28%, right mainstem intubation by 20%, superior vena cava perforation from a central venous catheter by 31%, normal film by 75%, negative pressure pulmonary edema by 16%, left lower lobe collapse by 80%, pulmonary infarction from a pulmonary artery catheter by 29%, and tension pneumothorax by 41%. Overall scores of the attending physicians were not significantly different from that of residents (p > 0.05). The control group of radiology residents scored significantly better (mean, 83.7; p = 0.009) than the anesthesia residents (mean, 62.8) and anesthesia attending physicians (mean, 62.5). CONCLUSION: Anesthesiologists are deficient in skills for the interpretation of chest radiographs. The skill level of university-based physicians is not greater than physicians in private practice, and skill level does not improve with level of training or experience. Most anesthesiologists rely on radiologists for interpretative results. Further training during the residency years may help improve diagnostic skills.     

Disturbed hypothalamic-pituitary axis in idiopathic recurring hypersomnia syndrome

Disturbed function of the hypothalamic-pituitary axis at adrenal and thyroid levels was found during an episode of hypersomnia in the idiopathic recurring hypersomnia syndrome. These endocrinological abnormalities, abolished ACTH and cortisol responses to insulin-induced hypoglycemia and absent TSH response to TRH, normalised thereafter in the symptom-free interval. These data support the hypothesis that Kleine-Levin syndrome is related to an intermittent hypothalamic dysfunction.     

Parkinson's disease in the elderly: response to and optimal spacing of night time dosing with levodopa.

1. Insomnia is an even more frequent complaint in elderly patients with Parkinson's disease than might be expected from the effect of age alone on sleep. 2. A double-blind, placebo-controlled trial in eleven patients with Parkinson's disease of mean (s.d.) age 80(5) years, showed that nocturnal dosing with levodopa produced a clinically significant improvement in sleep both as assessed subjectively and by measurement of number of spontaneous moves in bed. 3. Despite the long interval between tablet administration and morning assessment, walking time was faster on mornings following active treatment.