DIURNAL EFFECTS OF FLUOXETINE AND NALOXONE ON THE HUMAN HYPOTHALAMIC-PITUITARY-ADRENAL AXIS

1. Central serotonergic pathways are hypothesized to be involved in the stimulation of hypothalamic adrenocorticotropic hormone (ACTH) secretagogue release by both circadian- and stress-induced mechanisms. We aimed to investigate this hypothesis by measuring the effect of the highly specific serotonin re-uptake inhibitor fluoxetine (FX) on ACTH and Cortisol release in the morning and in the afternoon in humans, both by itself and in combination with the opioid antagonist naloxone (Nal). Naloxone causes ACTH release in humans by removing an endogenous inhibitory opioid tone on central noradrenergic pathways stimulatory to hypothalamic corticotropin-releasing hormone (CRH) secretion. Serotonergic agents may act directly or indirectly through these central noradrenergic pathways and, if so, would be expected to be additive to or synergistic with Nal in causing ACTH and Cortisol release. 2. Oral FX (40 mg) was given at approximately 07.00 or 11.00 h, either alone or with intravenous Nal 3 h later, to normal human volunteers. Plasma ACTH and Cortisol levels were measured for 5 h after FX dosing. 3. Fluoxetine produced a small but non-significant increase in Nal-stiimilated ACTH and Cortisol release in both morning and afternoon studies. Naloxone alone did not cause different ACTH and Cortisol responses in the morning and afternoon. 4. These results suggest that serotonergic pathways are not major regulators of the hypothalamic-pituitary-adrenal axis in humans or that FX has counteracting acute inhibitory effects on the axis, such as inhibition of hypothalamic arginine vasopressin secretion, which has been demonstrated in chronic animal studies.     

Aicardi–Goutières syndrome presenting with haematemesis in infancy

Aicardi–Goutières syndrome is a genetic childhood encephalopathy characterized by basal ganglia calcification, chronic cerebrospinal lymphocytosis and elevated cerebrospinal fluid interferon-alpha, mimicking acquired congenital viral infections. As more is discovered about the pathogenesis of Aicardi–Goutières, it is becoming evident that a dysfunction of the immune system is likely to be responsible for the disease phenotype. We describe a previously healthy 2-month-old female infant who presented with haematemesis and seizures and was subsequently diagnosed with Aicardi–Goutières syndrome. To our knowledge, this is the first documented case of Aicardi–Goutières syndrome presenting with haematemesis. The gastrointestinal tract is an area of high cell loss, revealing early signs of systemic inflammation and we postulate that a systemic proinflammatory milieu occurs in Aicardi–Goutières syndrome.
Conclusion: Aicardi–Goutières syndrome can present with haematemesis, adding to the growing evidence that the Aicardi–Goutières syndrome spectrum encompasses an immune-mediated multisystem involvement. Gastrointestinal inflammation should also be considered in these patients and treated appropriately.     

7.5%氯化钠对重症急性胰腺炎肾素-血管紧张素系统过度激活介导的全身炎症反应综合征的影响

目的探讨7.5%Nacl对重症急性胰腺炎时肾素-血管紧张素系统过度激活对大鼠多器官功能损害的保护机制.方法雄性健康SD大鼠64只随机分成4组:假手术对照组(sham):模型组(SAP);平衡盐组(L.R);7.5%高渗盐水组(H.S).动态定量测定血浆血管紧张素Ⅱ(AngⅡ)、内毒素(LPS)、血清TNF-α的变化,免疫组化检测肝组织NF-κ B p65和肠组织ICAM-1的表达,并在光镜下观察肝、肺及肠组织病理学改变.结果L.R组血浆中AngⅡ、TNF-α、LPS水平虽较SAP组低,但与sham组相比明显升高(P＜0.01).H.S组AngⅡ、TNF-α和LPS水平较L.R组显著降低(P＜0.01),SAP组和L.R组的NF-κB p65在汇管区肝细胞核中呈强表达,同时肠组织中ICAM-1表达显著增加,与H.S组相比差异有显著性(P＜0.01).H.S组肝、肺及肠组织病理损害亦明显减轻.结论高渗钠盐能通过抑制肾小球旁细胞释放肾素显著改变了AngⅡ水平,迅速降低AngⅡ这一炎症反应前的因子,减轻或阻断了SAP复苏后依然存在的内脏缺血所致全身炎症反应综合症,这可能是高渗盐治疗SAP的主要机制.过度应激反应在SAP持续发展和SIRS的发生、发展中起了重要的介导作用.     

Influence of pathological tumour variables on long-term survival in resectable gastric cancer

Although tumour stage and nodal status are established prognostic factors for resectable gastric cancer, the relative importance of other pathological characteristics remains unclear. This study reports univariate and multivariate analyses of the prognostic value of various pathological and staging factors based on 324 patients entered into the MRC randomised surgical trial for gastric cancer. In the univariate analysis tumour stage, nodal status, UICC clinical stage, number of involved nodes, WHO predominant type, mixed Lauren type, Ming type, tumour differentiation, lymphocytic and tumour stromal eosinophilic infiltration were all found to have a significant impact on survival (logrank test, 5% level). In the multivariate analysis, UICC clinical stage and eosinophilic infiltration were found to have a significant influence. Risk of death increased for UICC stage II and III patients (Hazard Ratio for stage II compared to stage I=2.0, 95% Confidence Interval (CI) 1.4-2.9; Hazard Ratio for stage III compared to stage I=3.5, 95% CI 2.5-4.8). Patients with numerous eosinophils had a lower risk of death than those with none (Hazard Ratio=0.5, 95% CI 0.3-0.8). This association between survival and eosinophilic infiltration merits further study.