Indomethacin increases the effect of isosorbide dinitrate on cerebral hemodynamic in migraine patients: pathogenetic and therapeutic implications

Intracerebral vascular reactivity induced by the nitric oxide (NO) donor isosorbide dinitrate (IDN, 5 mg sublingually) is more major and longer-lasting in migraine patients who develop delayed headache in response to the drug. The headache is purportedly due to neuronally-mediated vascular mechanisms. Indomethacin inhibits prostaglandin synthesis, which is involved in NO generation. Indomethacin also decreases cerebral blood flow by constricting precapillary resistance vessels. In the present study, the hemodynamic effects of indomethacin were evaluated in migraine patients and healthy controls by means of transcranial Doppler monitoring. Indomethacin caused a significant decrease in mean flow velocity in the middle cerebral artery. This was an additional effect to the mean velocity decrease induced by IDN. The interactions between the two drugs suggest that their effects on cerebral hemodynamics (and pain) may be of relevance both in understanding the role of NO in migraine pathogenesis and in evaluating symptomatic treatments for migraine attacks.     

Lack of biliary excretion of Cd linked to an inherent defect of the canalicular isoform of multidrug resistance protein (cMrp) does not abnormally stimulate accumulation of Cd in the Eisai hyperbilirubinemic (EHB) rat liver

A new mutant, the Eisai hyperbilirubinemic (EHB) rat, shows no inherent expression of the canalicular isoform of the multidrug resistance protein (cMrp) in the liver. It has defective biliary secretion of organic anions such as bilirubin glucuronides, bromosulfophthalein (BSP), cysteinyl leukotrienes, glutathione (GSH) and bile acid sulfate and glucuronides. When rats were injected intravenously with CdCl₂, biliary excretion of Cd over 30 min was 0.28% and 0.004% of the total dose in Sprague-Dawley (SD) and EHB rats, respectively. Six SD rats and five EHB rats were fed a diet containing Cd. Bile Cd was detected at the level of 2 ng/20 min in SD rats, but not in EHB rats. There was no significant difference of hepatic Cd concentration between SD and EHB rats. Furthermore, there were no significant differences of renal and intestinal Cd, and hepatic and renal metallothionein (MT) concentrations between the SD and EHB groups. Biliary excretion of reduced-GSH for 20 min was 1.3 ± 0.3 mg and 3.6 ± 0.9 μg in SD and EHB rats, respectively. Our results suggest that hepatobiliary excretion of exogenous Cd is mediated mainly via carrier transport, including a cMrp or GSH carrier, but that the lack of the transport pathway does not contribute to abnormal accumulation of Cd in the liver. Received: 12 August 1996 / Accepted 7 November 1996     

Combination of ABO blood group incompatibility and glucose-6-phosphate dehydrogenase deficiency: effect on hemolysis and neonatal hyperbilirubinemia

The incidence (%) of hyperbilirubinemia (serum bilirubin ≥257 μmol/l) was similar in neonates with a combination of ABO incompatibility and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (45%), with ABO incompatibility (54%) or G-6-PD deficiency (37%), alone (ns). Carboxyhemoglobin values, corrected for inspired CO, were similarly elevated in all three groups (0.87 ± 0.32%, 0.82 ± 0.29%, 0.76 ± 0.18%, respectively, ns), but correlated with bilirubin only in those with ABO incompatibility alone. ABO-incompatible/G-6-PD-deficient neonates, compared with those with either condition alone, are not at increased risk for hemolysis or hyperbilirubinemia.     

The future of outcomes measurement: item banking,tailored short-forms,and computerized adaptive assessment

The use of item banks and computerized adaptive testing (CAT) begins with clear definitions of important outcomes, and references those definitions to specific questions gathered into large and well-studied pools, or “banks” of items. Items can be selected from the bank to form customized short scales, or can be administered in a sequence and length determined by a computer programmed for precision and clinical relevance. Although far from perfect, such item banks can form a common definition and understanding of human symptoms and functional problems such as fatigue, pain, depression, mobility, social function, sensory function, and many other health concepts that we can only measure by asking people directly. The support of the National Institutes of Health (NIH), as witnessed by its cooperative agreement with measurement experts through the NIH Roadmap Initiative known as PROMIS (www.nihpromis.org), is a big step in that direction. Our approach to item banking and CAT is practical; as focused on application as it is on science or theory. From a practical perspective, we frequently must decide whether to re-write and retest an item, add more items to fill gaps (often at the ceiling of the measure), re-test a bank after some modifications, or split up a bank into units that are more unidimensional, yet less clinically relevant or complete. These decisions are not easy, and yet they are rarely unforgiving. We encourage people to build practical tools that are capable of producing multiple short form measures and CAT administrations from common banks, and to further our understanding of these banks with various clinical populations and ages, so that with time the scores that emerge from these many activities begin to have not only a common metric and range, but a shared meaning and understanding across users. In this paper, we provide an overview of item banking and CAT, discuss our approach to item banking and its byproducts, describe testing options, discuss an example of CAT for fatigue, and discuss models for long term sustainability of an entity such as PROMIS. Some barriers to success include limitations in the methods themselves, controversies and disagreements across approaches, and end-user reluctance to move away from the familiar.     

The interleukin-5 messenger RNA expression in a patient with idiopathic hypereosinophilic syndrome

Interleukin-5 has a specific role in various eosinophilic activities. It is the predominant cytokine produces by activated T-lymphocytes isolated from patients with idiopathic hypereosinophilic syndrome. We studied a young patient suffering from idiopathic hypereosinophilic syndrome who presented with Horner's syndrome, peripheral neuropathy and skin ulcers. The IL-5 gene expression by CD4⁺ T-lymphocytes and the peripheral eosinophil count were raised. The skin ulcers continued to deteriorate despite a swift reduction of the IL-5 gene expression and peripheral eosinophil count following systemic corticosteroid treatment. We suggest that peripheral eosinophilia may not be responsible for the damage in skin lesions and more aggressive treatment may be required.     

Neurotrophin-like immunoreactivity in the human pre-term newborn, infant, and adult cerebellum

The immunohistochemical occurrence of the neurotrophin (NT) proteins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4), and neurotrophin-3 (NT-3) is shown in the pre-term newborn, infant, and adult human post-mortem cerebellum. The NT-like immunoreactive structures were unevenly distributed and showed regional differences among cerebellar lobules and folia. NGF-, NT-4-, and NT-3-positive neuronal perikarya were observed in all specimens examined. At variance with the other neurotrophins, the BDNF antiserum labelled neuronal cell bodies only in newborn life and infancy, as well as extensive nerve fibre systems, whose density increased with age. The NT-antibodies, tested by Western blot on human cerebellum homogenates, revealed immunoreactive bands corresponding to proteins of heterogenous molecular weight. The results obtained provide a first demonstration of the tissue localization of the NTs in the human cerebellum from perinatal to adult age, thus suggesting their involvement in the development, differentiation and maintenance of the cerebellar connectivity. Codistribution of the four NTs or sets of them was observed in cortical and deep nuclei neurons. Multiple trophic roles for NTs, encompassing the classic target-derived and local mechanisms of support, are envisaged as significant in development, differentiation, and maintenance of the human cerebellar connectivity.     

显微定量法测定中成药中猪牙皂的含量

目的 :制定猪牙皂在脐风散与惊风散中的显微定量标准。方法 :用显微定量法 ,以猪牙皂特有的石细胞为显微特征物 ,对脐风散与惊风散中的猪牙皂进行测定。结果 :猪牙皂含量与每毫克特征数呈显著的线性正相关 ,回归方程为 y =61 .42 x -1 .1 0× 1 0 - 3(γ=1 .0 0 ,α=0 .0 5 )。结论 :显微定量法测定脐风散与惊风散中猪牙皂的含量是可行的 ,结果可靠     

老年病人睡眠状况及护理干预研究进展

综述了老年人睡眠质量及其影响因素、睡眠障碍的危害、老年病人睡眠的护理干预。建议进行前瞻性干预试验,为改善老年人的睡眠质量提供依据。     

葡萄球菌属对常用抗生素耐药情况调查

目的：了解葡萄球菌属，特别是耐甲氧西林葡萄球菌（MRS）的耐药情况，为临床用药提供参考。方法：从2002年1－7月送检的住院病人的血、痰、脓液、分泌物等标本中分离出的金黄色葡萄球菌、表皮葡萄球菌及其他血浆凝固酶阴性的葡萄球菌共105株，并进行药敏和多重耐药分析。结果：MRS的分离率较高，为68．6％，耐甲氧西林金黄色葡萄球菌（MRSA）为69．2％；耐甲氧西林表皮葡萄球菌（MRSE）为63．3％。MRS较非耐甲氧西林葡萄球菌（MSS）耐药率明显高，且MRS比MSS多重耐率高得多；MRSA对四种不同作用机制的抗生素；泰能、阿米卡星、环丙沙星、复方新诺明具有很高的多重耐药率，达到50％以上。结论：鉴于MRS的高分离率和多重耐药率，在治疗感染性疾病时，应加强病原学检查，提高标本鉴定的阳性率；在有效的治疗MRS感染的同时还应注意遏制MRS的产生。     

基因芯片筛选大肠侧向发育型肿瘤相关基因的初步研究

目的 应用基因芯片初步筛选大肠侧向发育型肿瘤(LST)相关基因，为进一步研究大肠癌的发病机制提供新的思路和线索。方法 抽提大肠侧向发育型肿瘤癌细胞株、SW480细胞株、LoVo细胞株的总RNA并纯化mRNA；将18816种人类基因及LST片段PCR产物用Bioroboties公司的BG600点样仪点样于纤维膜上，制成基因芯片。将3个样品的mRNA分别逆转录合成探针并^33 P标记，同芯片杂交。严格洗片后Fuji film公司FLA 3000扫描仪扫描芯片信号图象，ArrayGauge 1．0软件分析比较3种细胞株中差异表达基因。结果和结论 在18816种人类基因中存在着一系列LST同普通大肠癌细胞株之间的差异表达基因。在本研究中共有差异表达基因97个，其中共上调58个，共下调39个。表明其可能存在不同的肿瘤发生机制．故进一步研究其相关基因，在分子水平上阐明其发生机制及与大肠癌的关系具有重要意义。