Dual Orexin Receptor Antagonist Attenuates Increases in IOP,ICP, and Translaminar Pressure Difference After Stimulation of the Hypothalamus in Rats

PurposeIntraocular pressure (IOP) remains the only modifiable risk factor for glaucoma progression. Our previous discovery that stimulation of nuclei within the hypothalamus can modulate IOP, intracranial pressure (ICP), and translaminar pressure difference (TLPD) fluctuations led us to investigate this pathway further. Our purpose was to determine the role of orexin neurons, primarily located in the dorsomedial hypothalamus (DMH) and perifornical (PeF) regions of the hypothalamus, in modulating these pressures.MethodsSprague Dawley rats were pretreated systemically with a dual orexin receptor antagonist (DORA-12) at 30 mg/Kg (n = 8), 10 mg/Kg (n = 8), or vehicle control (n = 8). The IOP, ICP, heart rate (HR), and mean arterial pressure (MAP) were recorded prior to and following excitation of the DMH/PeF using microinjection of the gamma-aminobutyric acid (GABA)_A receptor antagonist bicuculline methiodide (BMI).ResultsAdministration of the DORA at 30 mg/Kg significantly attenuated peak IOP by 5.2 ± 3.6 mm Hg (P = 0.007). During the peak response period (8–40 minutes), the area under the curve (AUC) for the 30 mg/Kg DORA cohort was significantly lower than the control cohort during the same period (P = 0.04). IOP responses for peak AUC versus DORA dose, from 0 to 30 mg/Kg, were linear (R² = 0.18, P = 0.04). The ICP responses during the peak response period (4–16 minutes) versus DORA dose were also linear (R² = 0.24, P = 0.014). Pretreatment with DORA significantly decreased AUC for the TLPD following stimulation of the DMH/PeF (10 mg/kg, P = 0.045 and 30 mg/kg, P = 0.015).ConclusionsDORAs have the potential to attenuate asynchronous changes in IOP and in ICP and to lessen the extent of TLPDs that may result from central nervous system (CNS) activation.     

Cardiac ventricular support. Considerations for psychiatry.

Cardiac ventricular support is fostering additional roles for psychiatric consultation with this vulnerable end-of-life cardiac group. Incidence of premorbid and postsurgical psychiatric disorders (Axis I), psychotropic use, neurologic events, and mortality was obtained for 21 Novacor left-ventricular assist system patients prospectively and 13 Abiomed left/right ventricular-assist device patients retrospectively. This fragile patient population and their families warrant involvement for psychiatry because of the extreme conditions and consequences associated with mechanical cardiac assistance. The authors address psychiatric morbidity and neurobehavioral modifications associated with ventricular support.     

Paediatric experiences with work‐hour limitations

Objectives To evaluate the perceived impact of work‐hour limitations on paediatric residency training programmes and to determine the various strategies used to accommodate these restrictions. Methods A three‐page pre‐tested survey was administered to programme directors at the 2004 Association of Paediatric Programme Directors meeting. The impact of work‐hours was evaluated with Likert‐type questions and the methods used to meet work‐hour requirements were compared between large programmes (≥30 residents) and small programmes. Results Surveys were received from 53 programme directors. The majority responded that work‐hour limitations negatively impacted inpatient continuity, time for education, schedule flexibility and attending staff satisfaction. Supervision by attending staff was the only aspect to significantly improve. Perceived resident satisfaction was neutral. To accommodate work‐hour limitations, 64% of programmes increased clinical responsibility to existing non‐resident staff, 36% hired more non‐resident staff and 17% increased the number of residents. Only one programme hired additional non‐clinical staff. Large programmes were more likely to use more total methods on the inpatient wards (P < 0.01) and in the intensive care units (P < 0.05) to accommodate work‐hour limitations. Conclusions Programme directors perceived a negative impact of work‐hours on most aspects of training without a perceived difference in resident satisfaction. While a variety of methods are used to accommodate work‐hour limitations, programmes are not widely utilizing non‐clinical staff to alleviate clerical burdens.     

Intensity of antianginal therapy in patients referred for coronary angiography: a comparison of fee-for-service and health maintenance organization therapeutic strategies

BACKGROUND: No formal criteria have been developed to guide medical therapy for angina prior to revascularization, and no comparisons have been made between health maintenance organization (HMO) and fee-for-service (FFS) hospitals with respect to angina treatment. HYPOTHESIS: Using a literature-based measure of medical intensity, we tested the hypothesis that there is no difference in anginal medical therapeutic intensity between HMO and FFS systems. METHODS: For each antianginal drug, we developed a model from which an intensity score between 0 and 100 could be calculated. Average and maximal daily doses of drug were fit to a sigmoid curve such that they represented scores of 50 and 99, respectively. Overall intensity scores were obtained by weighted and unweighted averaging of three scores from nitrates, calcium-channel blockers, and beta blockers. This model was applied to 199 patients undergoing angiography at an FFS and an HMO hospital. RESULTS: HMO patients were taking more classes of antianginal drug (1.9 vs. 1.0, p < 0.001). Overall unweighted (17.7 vs. 11.7, p = 0.02) and weighted (27.3 vs. 16.9, p = 0.003) intensity scores for both HMO and FFS patients were low. HMO intensity scores for the use of beta blockers were greater than FFS scores (19.2 vs. 9.6, p = 0.002). The intensity scores for the use of nitrates and calcium blockers were similar. CONCLUSIONS: Models for the measurement of anginal medical therapy intensity can provide important information regarding medical therapy prior to revascularization. The overall intensity of medical therapy was low in both health care systems. These findings have important implications for patient management, guideline development, and national healthcare policy.     

耳穴贴压治疗单纯性肥胖症临床研究

目的探讨耳穴贴压治疗单纯性肥胖症的临床效应。方法应用耳穴贴压治疗单纯性肥胖症，观察治疗前后患者肥胖指标、血脂指标等的变化，评测耳穴贴压减肥的效果。结果各项指标在治疗前后差异均有显著性。结论耳穴贴压治疗单纯性肥胖，疗效确切，对患者各项生理指标有良性调节作用。     

History of safe use as applied to the safety assessment of novel foods and foods derived from genetically modified organisms

Very few traditional foods that are consumed have been subjected to systematic toxicological and nutritional assessment, yet because of their long history and customary preparation and use and absence of evidence of harm, they are generally regarded as safe to eat. This ‘history of safe use’ of traditional foods forms the benchmark for the comparative safety assessment of novel foods, and of foods derived from genetically modified organisms. However, the concept is hard to define, since it relates to an existing body of information which describes the safety profile of a food, rather than a precise checklist of criteria. The term should be regarded as a working concept used to assist the safety assessment of a food product. Important factors in establishing a history of safe use include: the period over which the traditional food has been consumed; the way in which it has been prepared and used and at what intake levels; its composition and the results of animal studies and observations from human exposure. This paper is aimed to assist food safety professionals in the safety evaluation and regulation of novel foods and foods derived from genetically modified organisms, by describing the practical application and use of the concept of ‘history of safe use’.     

Sleep related upper airway obstruction in a cohort with Down's syndrome.

The prevalence of sleep related upper airway obstruction (UAO) was studied in a cohort of 34 children with Down''s syndrome from a geographically defined area. Thirty two (94%) of the children, ranging in age between 0.1 and 4.9 years (median 1.4), underwent full clinical assessment for UAO including parental questionnaires and overnight tape recordings of chest wall movements and arterial oxygen saturation (SaO2). Compared with controls, children with Down''s syndrome had (a) an increased incidence of stridor and chest wall recession during sleep, (b) an increased frequency of a pattern on inspiration indicating increased upper airway resistance, (c) a reduced baseline oxygen saturation (having excluded recordings on four children with potential for right to left intracardiac shunting), and (d) an increased number of episodes with SaO2 less than or equal to 90% despite continued chest wall movements. At their initial assessment seven children (22%) had evidence of UAO. The 18 youngest children (less than or equal to 1.7 years) underwent repeated recordings and clinical assessment until they had all reached 2 years of age. A further three were found to have developed UAO. Sleep related UAO is a common problem in children with Down''s syndrome, occurring in 10 of 32 (31%) of this population based sample.