Subnuclear organization of the efferent connections of the parabrachial nucleus in the rat

In summary, we have demonstrated the subnuclear organization of PB, and correlated this with the origins of its efferent connections. In general, PBm projects primarily to the insular, infralimbic and lateral frontal cortex, and to associated areas in the thalamus, hypothalamus and amygdala. PBl chiefly innervates the autonomie nuclei of the hypothalamus and related portions of the amygdala and the bed nucleus of the stria terminalis. KF is the main source of descending projections from PB to the region of the nucleus of the solitary tract, the ventrolateral medulla and the intermediolateral cell column in the thoracic spinal cord. Further subnuclear organization of the origins of these projections within the major PB subdivisions has been described in detail.While PB afferents tend to terminate in specific subnuclei, one cannot reliably predict from the functional properties of the major inputs to a subnucleus what information will be carried in its efferents. Further anatomical and physiological studies of the input-output relationships of single PB neurons will be necessary to help resolve this enigma. However, recent immunohistochemical observations suggest that the subnuclear organization of PB afferent and efferent connections may reflect, at least in part, their biochemical specificity.     

Central neurogenic hyperventilation: a case report and discussion of pathophysiology

BACKGROUND: Central neurogenic hyperventilation is a rare condition with poorly understood pathophysiology. OBJECTIVE: To describe a patient with central neurogenic hyperventilation caused by an infiltrative brainstem lymphoma. CONCLUSION: Based on analysis of this patient and other case reports, we propose that central neurogenic hyperventilation is uniquely the result of infiltrative tumors that stimulate pontine respiratory centers and central chemoreceptors.     

The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects

BACKGROUND: The authors investigated whether the sedative, or hypnotic, action of the general anesthetic dexmedetomidine (a selective alpha -adrenoceptor agonist) activates endogenous nonrapid eye movement (NREM) sleep-promoting pathways. METHODS: c-Fos expression in sleep-promoting brain nuclei was assessed in rats using immunohistochemistry and hybridization. Next, the authors perturbed these pathways using (1) discrete lesions induced by ibotenic acid, (2) local and systemic administration of gamma-aminobutyric acid receptor type A (GABA ) receptor antagonist gabazine, or (3) alpha2-adrenoceptor antagonist atipamezole in rats, and (4) genetic mutation of the alpha -adrenoceptor in mice. RESULTS: Dexmedetomidine induced a qualitatively similar pattern of c-Fos expression in rats as seen during normal NREM sleep, a decrease in the locus ceruleus (LC) and tuberomammillary nucleus (TMN) and an increase in the ventrolateral preoptic nucleus (VLPO). These changes were attenuated by atipamezole and were not seen in mice lacking functional alpha2a-adrenoceptors, which do not show a sedative response to dexmedetomidine. Bilateral VLPO lesions attenuated the sedative response to dexmedetomidine, and the dose-response curve to dexmedetomidine was shifted right by gabazine administered systemically or directly into the TMN. VLPO lesions and gabazine pretreatment altered c-Fos expression in the TMN but in not the LC after dexmedetomidine administration, indicating a hierarchical sequence of changes. CONCLUSIONS: The authors propose that endogenous sleep pathways are causally involved in dexmedetomidine-induced sedation; dexmedetomidine's sedative mechanism involves inhibition of the LC, which disinhibits VLPO firing. The increased release of GABA at the terminals of the VLPO inhibits TMN firing, which is required for the sedative response.     

Nefazodone for chronic daily headache prophylaxis: an open-label study

OBJECTIVE: To assess effectiveness, tolerability, and safety of nefazodone as a prophylactic agent for chronic daily headache. BACKGROUND: Nefazodone is a potent, selective 5-HT2 antagonist with a distinct and atypical mechanism of action. The evolution of intermittent migraine to chronic daily headache has been linked to up-regulation of 5-HT2 receptors as well as other factors. Other effective migraine prophylactic medications are also 5-HT2 antagonists. Although research has shown nefazodone to be an effective antidepressant with a good tolerability and safety profile, its potential role in headache prophylaxis has not been tested. DESIGN: This was a two-center, open-label study with a 4-week baseline, followed by 12 weeks of treatment with nefazodone at a median dose of 300 mg (mean, 303.66 +/- 65.57 mg; range, 100 to 450 mg depending on tolerability). Potential patients were required to report more than 15 days of headache per month for at least 3 months prior to screening. Only patients with at least 15 days of recorded headache during baseline were included in the final sample (N=52). Most patients (n=48) had a history of migraine based on International Headache Society criteria; 4 had primarily chronic tension-type headache, but with more migrainous features than permitted by International Headache Society criteria for a primary chronic tension-type headache diagnosis. RESULTS: Significant improvement was demonstrated for all headache diary measures, with significance levels ranging from P<.00001 for average intensity, duration, headache index (intensity x duration), peak intensity, headache days per week, and peak impairment, to P<.0033 for severe headache days per week, and P<.0051 for rescue medication days. During the last month of treatment, 71% of the patients completing the study showed at least a 50% reduction in headache index compared to baseline, and 59% had at least a 75% improvement. Visual analog scales completed at 4-week intervals showed significant improvement in patient ratings of overall headache status, quality of life, sleep, mood (P<.00001), and sexual function (P<.00053). Significant improvements were also observed in the Pain Disability Index (P<.00007), Beck Depression Inventory-II (P<.00001), Hamilton Rating Scale for Depression (P<.0008), and Hamilton Psychiatric Rating Scale for Anxiety (P<.00007). Headache indices for patients in the top quartile on the depression and anxiety scales (clinical depression/anxiety) did not differ from the other patients during baseline. However, patients who were depressed or anxious showed significantly more improvement over the course of 12 weeks of treatment (P<.0006 or less for the depression scales, P<.026 for anxiety). Common mild to moderate adverse events reported by 10% or more of the patients included fatigue, nausea, dry mouth, dizziness, sleep disturbance, blurred vision, irritability/nervousness, and sedation. Only 5 of the 52 patients discontinued the study due to adverse events: headache (2 patients), and nausea, sleep disturbance, and a drugged feeling (1 patient each). CONCLUSIONS: These results provide preliminary support for the efficacy of nefazodone in the prophylaxis of chronic daily headache. In this sample, nefazodone was safe and generally well tolerated. Patient ratings of sexual function improved over the course of treatment, in contrast to what is generally observed with most antidepressants. Nefazodone may be particularly beneficial for patients with chronic daily headache and comorbid depression. Further research is indicated.     

跟骨定量超声骨质测量参数与骨密度及骨组织形态计量学指标的关系

目的:分析跟骨定量超声骨质测量中各参数与骨密度及形态计量学指标的相关性。方法:选择2004-01/2005-12广州市第六人民医院和中山大学三院骨科小腿以上截肢患者38例,将其跟骨定量超声测定的超声振幅衰减平均值与健康青年人骨峰值进行比较,>-2.5 SD者为骨量正常组(12例),<-2.5 SD者为骨质疏松组(26例)。分别进行跟骨定量超声、双能X线骨密度测量仪及骨形态计量学测量,应用直线相关分析法分析跟骨定量超声测定中各参数与骨密度及骨组织形态计量学各指标的相关性。结果:38例全部进入结果分析。①骨质疏松组跟骨超声振幅衰减平均值和骨硬度指数值均小于骨量正常组(P<0.01)。②骨量正常组跟骨骨密度值显著高于骨质疏松组[(352±16),(233±14)mg/cm2,P<0.01]。③骨量正常组跟骨平均骨小梁间距或弥散度低于骨质疏松组而松质骨体积高于骨质疏松组(P<0.05)。④超声振幅衰减平均值和骨硬度指数与骨密度呈直线正相关(r=0.814,0.326,P<0.01,0.05)。⑤超声传播速度与骨小梁游离末端、平均骨小梁间距呈直线负相关(r=-0.688,-0.712,P<0.01),与小梁间连点数、松质骨体积呈直线正相关(r=0.672,0.794,P<0.01);骨硬度指数与平均骨小梁间距呈直线负相关(r=-0.358,P<0.05),与松质骨体积呈直线正相关(r=0.513,P<0.01)。结论:跟骨定量超声测量中,超声振幅衰减平均值能较好地反映骨的密度,超声传播速度能较好地反映骨的质量,而骨硬度指数能较综合地反映骨强度的改变。     

Sequence Analysis of the RNA Polymerase Gene of Foot-and-Mouth Disease Virus Serotype Asia1

The complete nucleotide (nt.) sequence of the RNA polymerase (3D) gene and 81 nt. in the 3-untranslated region of foot-and-mouth disease virus (FMDV) serotype Asia1 (IND63/72) was determined and compared with the sequence of other FMDV serotypes. The 3D genomic region was 1410 nt. long encoding 470 amino acids with an inframe stop codon (TAA) at nt. position 1411–1413. The deduced amino acid sequence of the protein showed 8 conserved motifs as reported in other picornaviruses, 2 of which are 100% identical across the serotypes. Antigenic regions in the polymerase protein were predicted and found to be located at the N-terminus of the protein. The phylogenetic analysis showed that the FMD viruses were segregated into different clusters based on geographical origin; the Asia1 virus did not cluster tightly with any of the geographical groups.