Corticosterone controls the developmental emergence of fear and amygdala function to predator odors in infant rat pups

In many altricial species, fear responses such as freezing do not emerge until sometime later in development. In infant rats, fear to natural predator odors emerges around postnatal day (PN) 10 when infant rats begin walking. The behavioral emergence of fear is correlated with two physiological events: functional emergence of the amygdala and increasing corticosterone (CORT) levels. Here, we hypothesize that increasing corticosterone levels influence amygdala activity to permit the emergence of fear expression. We assessed the relationship between fear expression (immobility similar to freezing), amygdala function (c-fos) and the level of corticosterone in pups in response to presentation of novel male odor (predator), littermate odor and no odor. CORT levels were increased in PN8 pups (no fear, normally low CORT) by exogenous CORT (3 mg/kg) and decreased in PN12 pups (express fear, CORT levels higher) through adrenalectomy and CORT replacement. Results showed that PN8 expression of fear to a predator odor and basolateral/lateral amygdala activity could be prematurely evoked with exogenous CORT, while adrenalectomy in PN12 pups prevented both fear expression and amygdala activation. These results suggest that low neonatal CORT level serves to protect pups from responding to fear inducing stimuli and attenuate amygdala activation. This suggests that alteration of the neonatal CORT system by environmental insults such as alcohol, stress and illegal drugs, may also alter the neonatal fear system and its underlying neural control.     

Endocrine changes in Alzheimer's disease

In conclusion, at present, no consistent endocrine abnormalities can be detected in patients suffering from Alzheimer's disease. However, assessment of neuroendocrine function might help identify subpopulations of patients with particular neurotransmission abnormalities who are likely to benefit from a specific pharmacologic strategy. For example, patients in whom cholinomimetic drugs produce the greatest elevation in plasma cortisol concentration appear to derive the most symptomatic benefit from these drugs.     

Factors associated with recovery and recurrence of depression in older people: A prospective study

The Liverpool Continuing Health in the Community Study has followed up 1070 elderly community subjects over 6 years. In the first year 123 subjects had case-level depression. Three years later 49 (39.8%) of the previously depressed were recovered, 33 (26.8%) were depressed, 16 (13%) were not available for interview and 25 (20.3%) were dead. This study looks at factors associated with the 3-year outcome of patients who were depressed at year 0. Two outcome groups that were compared were a recovered depression group and a recurrent/persistent depression group. The factors that were significantly associated with a recurrence of depression (or persistent depression) at year 3 were bereavement of a close figure in the 6 months before interview, loneliness and life dissatisfaction at year 3. A variety of traditional risk factors for depression (including age, marital status, physical ill-health and incapacity) failed to attain significance in predicting recurrent or persistent depression. When combined, both recovered and recurrently depressed groups at year 3 had significantly higher levels of pain and a higher number of serious upsets in the past 6 months and 6 weeks compared to a compared to a control group. The depressed at year 0 were more likely to have entered more dependent forms of accommodation by year 3.     

A PACU crisis: a case study on the development and management of methemoglobinemia.

The development of methemoglobinemia requires rapid recognition, confirmation, and treatment. This case study describes the development, diagnosis, and management of a 63-year-old male scheduled for a laparoscopic cholecystectomy with an intraoperative cholangiogram who developed methemoglobinemia after benzocaine was given for intubation.     

Therapeutic review: antibiotic prophylaxis for bacterial endocarditis

A recent survey of antibiotic prophylaxis found that local practice often differed from that recommended by authoritative bodies such as the British Society for Antimicrobial Chemotherapy (BSAC) and the American Heart Association (AHA). Practitioners found the subject confusing and requested guidance. For these reasons we present current recommendations. Unfortunately all recommendations are based on animal studies and an understanding of the pathogenesis of bacterial endocarditis in humans. There are no controlled trials in humans on which to base guidelines, so rigidity is inappropriate. It is also important to realise that optimal prophylaxis will not eliminate bacterial endocarditis. In developed countries it has been estimated that only 10% of cases of endocarditis are theoretically preventable.     

Association and linkage with quantitative traits

This paper examines two approaches for the analysis of quantitative traits: (1) association studies and (2) linkage studies. The trait studied was Q1 from simulated Problem 2 data set in Genetic Analysis Workshop 9. Our purpose was to evaluate associations present in the data, to identify nongenetic and genetic predictors of the trait, and to explore the simulated genome for linkage. Through the association study, we found evidence for the primary major gene associated with this trait. The linkage study found evidence of residual genetic effect acting through other traits. Adjustments of Q1 for Q2 and Q3 led to a failure to find significant effects of MG2 and MG3. This supports the suggestion that adjustment for genetically influenced traits for effects of other genetic traits can reduce the power to detect major gene effects. In summary, we detected the major gene directly associated with the trait of interest through association studies. Linkage analysis detected evidence for two other genes associated to a lesser degree with the trait. © 1995 Wiley-Liss, Inc.     

Dexamethasone and indomethacin do not affect brain edema following head injury in rats

Head trauma was induced in rats by a weight-drop device, falling over the exposed skull over the left hemisphere. The neurological state of the rats was evaluated by a neurological severity score at 1 h and 18 h post head trauma. At 18 h post head trauma, rats were decapitated and tissue from the vicinity of the injury and from a corresponding area in the contralateral hemisphere was taken for specific gravity (SG) determination using linear gradient columns. Slices were taken from the same sites for incubation in Krebs-Ringer solution, and the concentrations of prostaglandin (PG)E2, 6-keto-PGF1 alpha, and thromboxane B2 accumulated in the medium during 1 h were measured by radioimmunoassay. In one experimental group, rats were pretreated with intraperitoneal dexamethasone sodium phosphate (4 mg/kg) 18 and 2 h before head trauma, and a third dose was given 8 h post head trauma. Another group was treated with intraperitoneal indomethacin (10 mg/kg) 1 h before and 7 h after head trauma. Other groups were treated immediately and 8 h after head trauma with 4, 8, 15, or 30 mg/kg of dexamethasone sodium phosphate. Another group of rats was treated with free dexamethasone (10 mg/kg) right after head trauma and 8 h later. Head trauma induced edema, as expressed by decreased SG, in the left hemisphere of all traumatized rats. Neither treatment protocol affected the neurological severity score of the injured rats or the SG of the contused hemisphere. PG synthesis, on the other hand, was significantly reduced following indomethacin or free dexamethasone, both in sham and traumatized rats, but not in dexamethasone sodium phosphate-treated rats. We conclude that pretreatment with indomethacin, dexamethasone sodium phosphate, or dexamethasone, used in the present protocols, does not affect posttraumatic cerebral edema. Thus, the role of PGs as mediators of edema formation remains unclear.     

Compliance with recommended prophylaxis for venous thromboembolism: improving the use and rate of uptake of clinical practice guidelines

Summary.  Although several authoritative, evidence-based, guidelines for the prevention of venous thromboembolism (VTE) have been published, the use of VTE prophylaxis in routine clinical practice varies markedly. Even in orthopedic surgery, the indication for which prophylaxis is used most often, a significant proportion of surgeons do not use routine prophylaxis. When prophylaxis is used, guideline recommendations are often not followed. A number of factors may contribute to the under-use of guidelines. Physician-related factors include: a lack of awareness of, or familiarity with, the guidelines; a perception that VTE is not a significant problem or that VTE prophylaxis is ineffective; and concern about potential bleeding risks. The guidelines may also be perceived to be too complicated or difficult to apply in a routine manner. In addition, a lack of facilities or resources may also present a barrier to implementation of the guidelines. A number of strategies are being investigated in an attempt to improve compliance with guidelines for VTE prophylaxis. For example, the Investigators Against Thromboembolism (INATE) initiative has developed a simplified pocket guideline on VTE prophylaxis in orthopedic and trauma surgery in order to raise awareness of the current guideline recommendations.