Chronic Administration of Glucocorticoids Directly Upregulates Prepro-Neuropeptide Y and Y1-Receptor mRNA Levels in the Arcuate Nucleus of the Rat

The complete sequence of the cDNA encoding the neuropeptide Y (NPY) Y₁-receptor has recently been deduced from a rat brain library, and the presence of messenger ribonucleic acid (mRNA) encoding Y₁-receptor protein has been demonstrated within the brain. Using quantitative in situ hybridization histochemistry, the content and distribution of Y₁receptor and preproNPY mRNAs have been investigated in the hypothalamic arcuate nucleus of adrenalectomized rats receiving glucocorticoid replacement therapy for 12 days by means of either high doses of dexamethasone in their drinking water or by subcutaneous corticosterone pellets. Basal metabolic parameters such as weight gain or loss, blood glucose and plasma insulin were monitored: Dexamethasone treatment induced weight loss and a state of hyperinsulinemia with normoglycemia, while corticosterone treated animals displayed metabolic parameters identical to sham ADX animals. Within the arcuate nucleus of glucocorticoid treated animals, levels of Y₁receptor and preproNPY mRNAs were increased. In contrast, adrenalectomy itself had no effect upon Y₁-receptor mRNA levels or preproNPY mRNA levels in the arcuate nucleus. These studies demonstrate that glucocorticoids exert a stimulatory action on levels of Y₁-receptor mRNA and preproNPY mRNA levels in the hypothalamic arcuate nucleus. This is the first evidence to suggest that the expression of a neuropeptide-receptor gene in the central nervous system may be directly sensitive to peripheral hormonal signals.     

Inhibin and age in men

OBJECTIVE: Normal elderly men are reported to have decreased testicular function despite elevated gonadotrophin levels. We wished therefore to determine if changes in testicular function occur over the age range 19-60 years. DESIGN: Single fasting blood samples were obtained between 0800 and 0900 h. PATIENTS: Working men in a large industrial company between the ages of 19 and 60 years participated in the study. MEASUREMENTS: FSH, serum immunoreactive inhibin and total testosterone were measured, the latter two as measurements of Sertoli and Leydig cell function respectively. RESULTS: The mean baseline serum immunoreactive inhibin level was significantly lower in men from the older age groups, 31-40 years (479 U/l), 41-50 years (439 U/l) and 51-60 years (415 U/l) than in men from the youngest age group, 21-30 years (613 U/l) while serum FSH was higher in men from the older age groups, 41-50 years (3.7 IU/l) and 51-60 years (6.1 IU/l) than in men from the youngest age group, 21-30 years (2.6 IU/l). There appears to be a change in both FSH and inhibin production, consistent with a primary decline in testicular function. There was no significant difference in testosterone levels between the older age group, age 51-60 years and the younger age group, age 21-30 years. However, testosterone levels were significantly lower in the 41-50 year age group, when compared with the 21-30 year, this significance levelling out at about age 45 years. CONCLUSION: The data are consistent with the hypothesis that immunoreactive inhibin reflects inhibin bioactivity, and that inhibin plays a role in the feedback control of FSH secretion in men.     

Coronary atherosclerosis in cardiac transplant patients treated with total lymphoid irradiation.

BACKGROUND: Multiple episodes of rejection following cardiac transplantation have been associated with an increased incidence of coronary atherosclerosis. Total lymphoid irradiation (TLI) has been shown to be a successful treatment for persistent allograft rejection, but its effect on coronary arterial disease has yet to be evaluated. METHODS: From 1987 to 1999, 40 patients required TLI for persistent or recurrent allograft rejection following heart transplantation. Each patient's (Group 1, n = 31) post-transplant coronary angiograms were examined and compared with those of a control group (Group 2, (n = 32) matched for time of transplantation. Degree of coronary stenosis was assessed on a 6-point scale. All patients received induction therapy (rabbit anti-thymocyte globulin or OKT3) and standard triple immunosuppressive therapy. TLI (80 cGy x 10 fractions) was used for the treatment of recurrent or persistent rejection on the basis of clinical indications. Actuarial survival, number and treatment of rejection episodes, and severity of coronary artery disease were compared in each group. RESULTS: Recipient gender, age, race and cytomegalovirus (CMV) status at time of transplant, along with donor gender, CMV status and graft ischemia time, were similar in both groups. Group 1 donor age was younger than that of Group 2 (22.2 +/- 11.2 vs 31.5 +/- 13.6 years, p = 0.004), and the indication for surgery in Group 1 patients was more likely to be ischemic heart disease (15 of 31 vs 6 of 32, p = 0.02). Mean follow-up was 5.7 +/- 3.5 years in Group 1 vs 6.9 +/- 3.8 in Group 2 (p = NS). Group 1 had more rejection episodes (4.4 +/- 2.2 vs 2.3 +/- 2.0, p = 0.0002) and more steroid treatments (9.78 +/- 4.0 g vs 5.14 +/- 4.7 g, p < 0.0001), but less coronary artery disease compared with Group 2 (p = 0.035). CONCLUSIONS: Despite multiple episodes of rejection, patients treated with TLI after cardiac transplant appear to develop less coronary atherosclerosis than appropriately matched controls.     

Gestational age and intrauterine growth retardation among white and black very low birthweight infants: a population-based cohort study

Summary. Very low birthweight (VLBW) is a commonly used endpoint in perinatal epidemiology, but the population of VLBW infants comprises a wide range of gestational ages and rates of fetal growth. We used data from a population-based study of all 1072 black and white VLBW liveborn infants born in 29 counties in Georgia between April 1986 and March 1988. Less than 1% of the VLBW infants were ≥ 37 weeks gestation; most were 29–32 weeks (26%) or 25 to 28 weeks (40%); 12% were 22 weeks or less. All infants 33 weeks gestation or greater were growth retarded. The population of VLBW infants seems to comprise three groups: approximately 11% very immature infants of 22 weeks or less; the majority of infants, born between 23 and 30 weeks, 90% of which are of normal weight for their gestational age; and a group of less premature, growth-retarded infants from 31 to 36 weeks. We found little or no difference in the distribution of gestational age or the percentage of intrauterine growth rates (IUGR) between black and white infants. In the USA the VLBW rate among black infants is over three times greater than that among white infants and consequently the rates of the three types of VLBW among black infants are likely to be triple those among white infants.     

Personal history,training, and worksite as predictors of back pain of nurses

Back pain among nurses is a common problem. Prior studies of this problem have been based on cross-sectional or retrospective data. This 18-month prospective study involving nurses newly graduated from nursing school investigated personal, worksite, and training factors associated with future risk of back pain. Each nurse underwent a preliminary interview and periodic follow-ups to identify those with back injuries. Contingency tables and logistic regression analyses demonstrated that prior significant back pain episodes (evidenced by previous job changes because of back pain, frequent medication use, etc.) were associated with increased future risk. Training at nursing school or on the job did not have a protective effect. This pilot study therefore suggests factors useful in placement and counseling of new nurses and indicates the need for further implementation of mechanical lift assist device use. © 1994 Wiley-Liss, Inc.     

Effects of Repeated Deep Inspirations on Recovery from Methacholine-Induced Airway Narrowing in Normal Subjects

Background. A single deep inspiration (DI) is known to be a potent bronchodilator but it is not known if repeated DI can accelerate sustained recovery from bronchoconstriction. Methods. We induced sustained bronchoconstriction using increasing concentrations of nebulized methacholine (Mch) during tidal breathing and assessed airway narrowing by measuring respiratory resistance (Rrs) using forced oscillation in six healthy subjects. On separate days we examined the effects of DI every 3 minutes and of prohibition of DI on recovery of Rrs for 30 minutes after the end of Mch nebulization. Results. Bronchoconstriction (Rrs ∼ 150% above baseline) was induced. DI during recovery had a transient bronchodilator effect but no cumulative effect. At 30 minutes after end of nebulization (and 2 minutes after the last DI) Rrs was 87% above baseline compared to 93% above baseline when DI was prohibited. Conclusion. Recovery from induced bronchoconstriction with methacholine was slow (∼ 2%/min) and not accelerated by frequent DI.     

Grand round cases: Australian Association of Neurologists Annual Scientific Meeting, Canberra 2006.

The Annual Scientific Meeting of the Australian Association of Neurologists includes a Grand Rounds Session in which unusual cases are presented. The Chairmen of the 2006 session, Drs Richard Stark and Heather Waddy, lead the audience through a discussion of the history, physical signs, diagnostic investigations and finally the diagnosis at intervals throughout the case presentation. In introducing the cases Dr. Stark emphasized that the cases were selected because they were unusual and the final diagnosis may not be evident at the outset. The approach to the clinical problems and the process of thinking through the differential diagnoses and the method of investigation were as important to the discussion of these cases as the final diagnosis itself. These cases are reported here including an edited summary of the discussion with the same emphasis on the method of clinical analysis and the diagnostic process.     

Atypical antipsychotics to treat the neuropsychiatric symptoms of dementia

Neuropsychiatric symptoms are common in older adults with dementia and can be associated with a rapid decline in cognitive and functional status. This article reviews the current literature supporting the use of atypical antipsychotic medications in this population. Among the currently available atypical antipsychotics, risperidone and olanzapine have been the most widely studied in double-blind, randomized, placebo-controlled clinical trials. Despite the common use of other atypical antipsychotic medications, their efficacy and safety in older adults with dementia has not been as extensively studied. Some controversy surrounds the use of atypical antipsychotic agents in older adults with the suggestion that they may increase the incidence of stroke or even death. Despite the potential for increased risk of harm from the use of these medications, atypical antipsychotics are often effective in treating troublesome neuropsychiatric symptoms refractory to other treatments. Whenever possible, these atypical antipsychotic drug treatments should be combined with non-pharmacological treatments to limit the need and dose of antipsychotic drugs and constant monitoring for potential harms should be maintained. The choice of which atypical antipsychotic agent can be guided by the nature and severity of the target symptom and the medication least likely to cause harm to the patient.