Experimental headache in humans

The need for valid human experimental models of headache is obvious. Several compounds have been proposed as headache-inducing agents, but only the nitroglycerin (NTG) model has been validated. In healthy subjects, intravenous infusions of the nitric oxide (NO) donor NTG induce a dose-dependent headache and dilatation of the temporal, radial and middle cerebral artery. NTG-induced headache, although less intense, resembles migraine in pain characteristics, but the accompanying symptoms are rarely present. Cephalic large arteries are dilated during migraine headache as well as during NTG headache. N-acetylcysteine enhances the formation of NO and potentiates NTG-induced headache, whereas mepyramine, a H1 -antagonist capable of blocking histamine-induced headache, has no effect. Thus, the headache is dependent on NO or other steps in the NO cascade. The model is useful for pharmacological interventions and sumatriptan reduced the NTG-induced headache. The NTG model may be a valuable tool in the development of future migraine drugs.     

Neutrophil dermatosis of the dorsal hands

Neutrophil dermatosis of the dorsal hands (NDDH) is a recently described skin manifestation regarded as a subset of acute febrile neutrophilic dermatotis (Sweet syndrome). We describe 5 cases with pustular and ulcerative plaques and/or bullae and vesicles of the dorsal hands. Three of the patients also had skin changes at sides other than the hands. Associated conditions were found in two patients, one patient treated with hemo-dialysis for chronic glomerulonephritis, and one patient had suffered from a streptococcal tonsillitis prior to the eruption. Two of the patients had fever, two had neutrophil leucocytosis in peripheral blood and two had elevated sedimentation rates. Histological findings showed signs of vasculitis in biopsies from two of the patients. NDDH is discussed on the basis of prior case reports concerning the subject, and it is concluded that Neutrophil dermatosis of the dorsal hands should be regarded as a localized variety of Sweet syndrome.     

多层螺旋CT评价先天性单冠状动脉畸形

目的 探讨16层螺旋CT（MSCT）冠状动脉造影诊断先天性单冠状动脉畸形的价值。资料与方法 回顾性分析4例先天性单冠状动脉患者的MSCT和常规X线冠状动脉造影（CCA）资料。对比两者在显示和诊断此病中的差异。仿真内镜技术用于评价异位开口及其与邻近正常冠状动脉开口的关系,多平面重建、曲面多平面重建、最大密度投影、容积成像等重建方法则用于评价变异冠状动脉的行径及其与邻近大血管的关系。结果 4例患者变异的冠状动脉全部为MSCT造影所显示并明确诊断。MSCT显示3例患者的左主干起源于右冠状动脉的近段,其中1例在CCA中左主干仅近段局部显影,未能明确诊断,另2例左冠状动脉虽显影,但较淡。1例右冠状动脉起源于左主干的末端,CCA则误为起源于回旋支。MSCT显示2例异常开口冠状动脉的近段狭窄,3支异常冠状动脉穿过主动脉根部和肺动脉或右室流出道的间隙,1支绕主动脉根部后方走行,而CCA均不能明确诊断。结论 MSCT显示先天性单冠状动脉明显优于CCA,凡疑及冠状动脉变异的患者,可首选非创伤性的MSCT冠状动脉造影检查。     

The role of the Child Health Services in the identification of children with possible Attention Deficit Hyperactivity Disorder/Deficits in Attention, Motor Control and Perception (ADHD/DAMP)

Literature concerning the role of the Child Health Services in the identification of children with possible Attention Deficit Hyperactivity Disorder/Deficits in Attention, Motor Control and Perception (ADHD/DAMP) is summarized in order to establish a background for evaluation, discussion and conclusion.     

Headache induced by a nitric oxide donor (nitroglycerin) responds to sumatriptan. A human model for development of migraine drugs

Experimental "vascular" headache in humans may be used in characterizing new migraine drugs. The effects of sumatriptan on nitroglycerin-(NTG)-induced headache and arterial responses were therefore studied. Following a double-blind randomized crossover design, 10 healthy volunteers received sumatriptan 6 mg s.c. or placebo succeeded by 20 min NTG (0.12 mg/kg/min) infusion. Headache was rated on a 10 points scale. Temporal and radial artery diameters and velocity in the middle cerebral artery (MCA) were measured with ultrasound. Sumatriptan reduced the NTG-induced headache, median score 1.5 versus 4 after placebo ( p <0.01) and decreased temporal and radial artery diameters 75±3 and 86±3% of baseline respectively ( p <0.05), Blood velocity in the MCA was unaffected. The NTG model may prove to be a valuable tool in the development of future migraine drugs. The results suggest that NTG headache in non-migraineurs may share mechanisms with migraine headache.     

The serine protease granzyme M is preferentially expressed in NK-cell,gamma delta T-cell,and intestinal T-cell lymphomas: evidence of origin from lymphocytes involved in innate immunity

Granzyme M (GM) is a novel serine protease whose expression is highly restricted to natural killer (NK) cells, CD3(+)CD56(+) T cells, and gamma delta T cells. Using a GM-specific monoclonal antibody, we analyzed the expression of GM in 214 mature T-cell and NK-cell lymphomas. GM was preferentially expressed in nasal NK/T-cell lymphomas (100%), gamma delta T-cell lymphomas (100%), and intestinal T-cell lymphomas (85%). In contrast, GM expression was present at low prevalence in mycosis fungoides/Sézary syndrome (3%), anaplastic large-cell lymphoma (6%), panniculitis-like T-cell lymphoma (11%), and angioimmunoblastic T-cell lymphoma (0%) cases. Peripheral T-cell lymphomas of unspecified subtype showed an intermediate frequency (37%) of GM expression, consistent with their heterogeneous origin. We conclude that GM expression is a distinctive feature of the nasal NK/T-cell, gamma delta T-cell, and intestinal T-cell lymphomas, and suggest that these tumors develop from lymphocytes involved in innate immunity.     

16层螺旋CT血管造影对冠状动脉狭窄的评价

目的:分析16层螺旋CT血管造影(MSCTA)无创性评价冠状动脉(冠脉)狭窄的价值.方法:80例临床初诊疑为冠心病,既往无冠脉成形术和搭桥术史的患者,行冠脉16层MSCTA后(其中9例在CT扫描前心率超过80次/min的患者应用了β受体阻滞剂),回顾性重建心电门控轴位图像,并分别采用容积成像、多平面重建、曲面重建、最大密度投影等后处理方法,对所有冠脉及其分支进行重建,统计可供临床评价的、管径≥1.5 mm的冠脉段,以选择性冠脉造影(SCA)为标准,对比分析MSCTA诊断冠脉显著性狭窄(管腔平均直径缩小>50%)的准确性.结果:94%(989/1056)的冠脉节段和94%(290/310)的冠脉主支可供评价,(6%)67/1056段不能评价的主要原因分别为:心脏运动伪影39段,致密钙化20段和管腔显影不良8段.除外不能评价的冠脉,按节段和主支分类,与SCA相比,MSCTA诊断冠脉显著性狭窄的差异无统计学意义,其敏感性、特异性、阳性和阴性预期值分别为93%、99%、87%、99%和95%、98%、91%及99%.结论:在患者心率<80次/min时,16层MSCTA即可获得较好的图像质量用于评价冠脉并判断其狭窄程度,是一种值得临床医生信赖的检查冠脉有无狭窄的无创伤性方法.     

The RAR-RXR as well as the RXR-RXR pathway is involved in signaling growth inhibition of human CD34+ erythroid progenitor cells

Previous studies have shown that retinoic acid (RA), similar to tumor necrosis factor-alpha (TNF-alpha), can act as a bifunctional regulator of the growth of bone marrow progenitors, in that it can stimulate granulocyte-macrophage colony-stimulating factor (GM-CSF)- or interleukin-3 (IL-3)-induced GM colony formation, but potently inhibit G-CSF-induced growth. The present study, using highly enriched human CD34+ as well as Lin- murine bone marrow progenitor cells, demonstrates a potent inhibitory effect of 9-cis-RA on burst-forming unit-erythroid (BFU-E) colony formation regardless of the cytokine stimulating growth. Specifically, 9-cis-RA potently inhibited the growth of BFU-E response to erythropoietin (Epo) (100%), stem cell factor (SCF) + Epo (92%), IL- 3 + Epo (97%), IL-4 + Epo (88%), and IL-9 + Epo (100%). Erythroid colony growth was also inhibited when CD34+ progenitors were seeded at one cell per well, suggesting a direct action of RA. Using synthetic ligands to retinoic acid receptors (RARs) and retinoid X receptors (RXRs) that selectively bind and activate RAR-RXR or RXR-RXR dimers, respectively, we dissected the involvement of the two retinoid response pathways in the regulation of normal myeloid and erythroid progenitor cell growth. Transactivation studies showed that both the RAR (Ro 13- 7410) and RXR (Ro 25-6603 and Ro 25-7386) ligands were highly selective at 100 nmol/L. At this concentration, Ro 13-7410 potently inhibited G- CSF-stimulated myeloid as well as SCF + Epo-induced erythroid colony growth. At the same concentration, Ro 25-6603 and Ro 25-7386 had little or no effect on G-CSF-induced colony formation, whereas they inhibited 75% and 53%, respectively, of SCF + Epo-stimulated BFU-E colony growth. Thus, the RAR-RXR response pathway can signal growth inhibition of normal bone marrow myeloid and erythroid progenitor cells. In addition, we demonstrate a unique involvement of the RXR-RXR pathway in mediating growth inhibition of erythroid but not myeloid progenitor cells.     

Plastic-adherent progenitor cells in mobilized peripheral blood progenitor cell collections

The use of peripheral blood progenitor cells (PBPC) to reconstitute hematopoiesis after high-dose chemoradiotherapy is now commonplace in the treatment of malignancies. Attempts to characterize these cells have concentrated primarily on their phenotype and their content of clonogenic colony-forming cells (CFC). We have used a plastic-adherent delta (P delta) assay system to evaluate the quantity and quality of more primitive cells in addition to the conventional measurements of CFC and CD34-positive cells. The leukapheresis products from 20 patients mobilized using cyclophosphamide (Cy) and granulocyte colony- stimulating factor (G-CSF) were examined for progenitor cell content. The mean number of mononuclear cells (MNC), colony-forming units- granulocyte/macrophage (CFU-GM), and CD34-positive cells from two leukaphereses per patients were 7.9 x 10(8)/kg, 47.3 x 10(4)/kg, and 10.5 x 10(6)/kg, respectively. The mean number of P delta progenitors was 9.3 x 10(4)/kg. Limiting dilution analyses showed the frequency of P delta progenitors in PBPC to be between 1 and 5.3 per 10(5) MNC and that each P delta progenitor has the proliferative capability to generate an overall mean of 4.5 CFU-GM. Of the 20 patients, 16 underwent autografting with PBPC alone. Fifteen patients engrafted neutrophils and platelets within 16 days. One patient had delayed engraftment associated with inadequate etoposide clearance. Statistical analysis showed a strong correlation between numbers of CFU-GM and CD34 positivity. The numbers of plastic-adherent P delta progenitor cells did not correlate with CFU-GM or CD34-positive cells. We conclude that the plastic-adherent P delta progenitor cell assay is capable of measuring primitive hematopoietic cells and that it may be useful for the investigation of primitive progenitors in PBPC harvests.