二羟丙氧甲基乌嘌呤抗单纯疱疹病毒Ⅰ型的实验研究

二羟丙氧甲基鸟嘌岭(DHPG),在组织培养中对单纯疱疹病毒Ⅰ型(HSV-1)KOS株抑制50%空斑形成的浓度(IC_(50))为0.1μg/ml。DHPG与环胞苷联合应用的抗HSV活性呈协同作用;DHPG分别与无环鸟苷、酞丁安合用有相加作用。0.1和0.05%DHPG溶液滴眼对家兔实验性浅层单纯疱疹病毒角膜炎有显著治疗作用,浓度降低至0.025和0.0l%无明显疗效。对实质层型单疱角膜炎,0.1%DHPG溶液滴眼治疗有效。     

Intranasal administration of growth hormone-releasing hormone(1–29)-NH2 in children with growth hormone deficiency: effects on growth hormone secretion and growth

The growth-promoting potential of growth hormone-releasing hormone(1— 29)-NH, (GHRH(1–29)- NH,) in a new formulation for intranasal use was examined in a 6-month pilot study of eight short prepubertal children. The maximal plasma concentration of growth hormone (GH) was below 12 μg/l in two stimulation tests (arginine, insulin), but above 12 (24–90) μg/l after intravenous GHRH, 1 μglkg. GHRH, 50 μg/kg, was insufflated intranasally three times per day over 6 months. On day 1, GHRHinsufflations were followed by distinct GHRH and GH plasma peaks, ranging from 1.2 to 5.4 μg/l and from 10 to 85 mIU/l, respectively. Peak amplitudes were variably reduced after 6 weeks in most patients, and further reduced at 6 months. GHRH antibodies (initially negative) were positive in three patients after 6 weeks. The mean knemometric growth rate rose from 0.24 to 0.48 mm/week after 6 weeks of treatment ( p = 0.03) and then rapidly declined; the mean 6-month stadiometric height velocity did not increase. Local tolerance was good in one patient; most others reported sneezing immediately after insufflation, rhinorrhoea and mild mucosal burning. Treatment was discontinued in two patients after 6 and 12 weeks. It is concluded that intranasal GHRH, though non-invasive, is not suitable in its present form for use in children, because of decreasing absorption and effectiveness with concomitant development of antibodies and local reactions.     

Chromosomal abnormalities in untreated patients with non-Hodgkin's lymphoma: associations with histology, clinical characteristics, and treatment outcome. The Nebraska Lymphoma Study Group

We describe the chromosomal abnormalities found in 104 previously untreated patients with non-Hodgkin's lymphoma (NHL) and the correlations of these abnormalities with disease characteristics. The cytogenetic method used was a 24- to 48-hour culture, followed by G- banding. Several significant associations were discovered. A trisomy 3 was correlated with high-grade NHL. In the patients with an immunoblastic NHL, an abnormal chromosome no. 3 or 6 was found significantly more frequently. As previously described, a t(14;18) was significantly correlated with a follicular growth pattern. Abnormalities on chromosome no. 17 were correlated with a diffuse histology and a shorter survival. A shorter survival was also correlated with a +5, +6, +18, all abnormalities on chromosome no. 5, or involvement of breakpoint 14q11-12. In a multivariate analysis, these chromosomal abnormalities appeared to be independent prognostic factors and correlated with survival more strongly than any traditional prognostic variable. Patients with a t(11;14)(q13;q32) had an elevated lactate dehydrogenase (LDH). Skin infiltration was correlated with abnormalities on 2p. Abnormalities involving breakpoints 6q11-16 were correlated with B symptoms. Patients with abnormalities involving breakpoints 3q21-25 and 13q21-24 had more frequent bulky disease. The correlations of certain clinical findings with specific chromosomal abnormalities might help unveil the pathogenetic mechanisms of NHL and tailor treatment regimens.     

莫达非尼治疗帕金森患者白天嗜睡的双盲安慰剂对照试验

研究背景: 过度白天嗜睡 (EDS)通常使得帕金森(PD)患者的病情更为复杂。EDS的病因是多因素的,多巴胺药物治疗可能会使之恶化。莫达非尼(modafinil)是一种促醒药物,被批准用于发作性嗜睡的治疗,但是却经常被用于各种嗜睡状态的治疗。     

The human homologue of rat NG2, a chondroitin sulfate proteoglycan, is not expressed on the cell surface of normal hematopoietic cells but is expressed by acute myeloid leukemia blasts from poor-prognosis patients with abnormalities of chromosome band 11q23

In our efforts to produce monoclonal antibodies that recognize cell- surface antigens expressed by hematopoietic precursor and stromal cells, we generated a monoclonal antibody, 7.1, which recognizes a 220- to 240-kD cell-surface protein whose N-terminal amino acid sequence is identical to the rat NG2 chondroitin sulfate proteoglycan molecule. This chondroitin sulfate proteoglycan, previously reported to be expressed by human melanoma cells, was not found to be expressed by normal hematopoietic cells, nor was it expressed on the cell surface of cell lines of hematopoietic origin including cell lines with 11q23 abnormalities. It was found on the cell surface of acute myeloid leukemia (AML) blasts and cell lines derived from nonhematopoietic tissues. Samples of leukemic marrow from 166 children with AML enrolled on Childrens Cancer Group protocol 213 were evaluated for cell-surface expression of this proteoglycan molecule. In 18 of 166 (11%) patient samples, greater than 25% of leukemic blasts expressed the NG2 molecule. These 18 patients had a poorer outcome with respect to survival (P = .002) and event-free survival (P = .035) with an actuarial survival at 4 years of 16.7%. Blast cell expression of the NG2 molecule was strongly associated with French-American-British M5 morphology (P < .0001) and abnormalities in chromosome band 11q23, site of the MLL gene. These results show that the NG2 molecule is expressed by malignant hematopoietic cells that have abnormalities in chromosome band 11q23, suggesting that antibody 7.1 may be useful in the rapid identification of this group of poor-prognosis patients.     

US of the biceps tendon apparatus

High-resolution real-time sonography of the biceps tendon was performed on 80 patients referred for shoulder arthrography. The arthrograms and sonograms were compared at the levels of the biceps tendon groove and distal tendon. Sonography and arthrography were equally successful in facilitating the evaluation of the bony configuration of the biceps tendon groove, but sonography gave a superior image of the biceps tendon within the groove. In 16 patients, biceps tendon sheath effusions or swelling was detected using sonography; 15 of these patients had associated pathologic conditions elsewhere in the joint. Arthrograms did not disclose a biceps tendon or sheath abnormality in any of these patients. We conclude that sonography could be the imaging method of choice in patients with suspected biceps tendon lesions and that the presence of a biceps tendon or sheath abnormality indicates an increased likelihood of abnormalities elsewhere in the joint.     

椎间盘退行性变的影响因子及其基因和组织工程结合基因治疗

目的:从各领域和不同角度探讨椎间盘退行性变的病因及其作用机制,并探索基因治疗及组织工程结合基因治疗对延缓或逆转早、中、晚期椎间盘退行性变的可能性。资料来源:应用计算机检索Pubmed数据库1998-06/2006-01有关椎间盘退行性变影响因子及生物学治疗进展的文章,检索词“intervertebral disc degeneration,nucleus pulposus,interleukin-1 beta,interleukin-6、interleukin-18,potential therapeutic model”,限定文章语言种类为English。同时检索VIP维普、CNKI中国期刊全文数据库2000-06/2006-08期间的相关文章,检索词“椎间盘退行性变、髓核、促炎因子、基因治疗”,限定文章语言种类为中文。资料选择:对资料进行初审,选取符合研究要求的有关文章找全文。纳入标准:①有关椎间盘退行性变影响因子的基础研究及临床研究。②有关基因治疗退行性变椎间盘的相关研究。③有关人工椎间盘移植的研究。排除标准:重复或类似的同一研究、个案报道等。资料提炼:共收集到123篇有关椎间盘退行性变影响因子及生物学治疗进展的文章,57篇符合研究要求(其中35篇为椎间盘退行性变影响因子基础研究方面的文献,22篇涉及基因治疗、人工椎间盘移植方面)。资料综合:①国内对椎间盘退行性变影响因子及治疗的研究:从椎间盘营养供应、细胞凋亡、基质酶活性、生物力学等方面研究与椎间盘退行性变有关的相关因素,如丝氨酸蛋白酶在退行性变椎间盘的终板中活性极高,基质金属蛋白酶3在细胞外基质成分的降解过程中起关键作用,还能通过激活其他非活性基质金属蛋白酶而对软骨基质的降解发挥间接作用。基质金属蛋白酶3表达阳性的细胞比例与MRI检查中的椎间盘退行性变程度有显著相关性,且突出型腰椎间盘中基质金属蛋白酶3表达阳性的细胞比例显著高于未突出型;;突出椎间盘组织可以诱导碱性成纤维细胞生长因子,且与突出类型、病程相关,提示碱性成纤维细胞生长因子在腰椎间盘组织退行性变、自发性吸收中有重要的促进作用等。并探讨相关基因(成骨蛋白1、骨形态发生蛋白7)在延缓或逆转椎间盘退行性变治疗上的可行性。②国外对椎间盘退行性变影响因子及治疗的研究:从以上几方面研究椎间盘退行性变的因素及机制,如胰岛素样生长因子和血小板来源的生长因子均可降低椎间盘细胞的凋亡指数,为该病的防治提供了新的思路;;白细胞介素1使椎间盘纤维环细胞产生的前列腺素E2和磷脂酶A2增加,减少纤维环中总的蛋白多糖含量;;最近研究发现白细胞介素18是强有力的致炎因子之一,在退行性变的关节软骨及椎间盘软骨终板呈一定表达,遂被认为在椎间盘退行性变中发挥重要作用,但少见报道。同时探索用腺相关病毒体外转染人椎间盘细胞,体内转染兔椎间盘细胞,并证实自体同源椎间盘细胞、同源软骨、同种异体的完整椎间盘或活性椎间盘细胞移植可以延缓椎间盘退行性变,又以腺病毒转染SV40基因的方法成功构建了永生化的人髓核细胞株,可作为组织工程椎间盘的种子细胞。③国内外关于椎间盘退行性变影响因子及治疗研究的展望:提供更多的临床样本,探索创新出更多、更细致的思路来综合研究椎间盘退行性变的可能机制和根本治疗方法。结论:椎间盘退行性变的确切机制目前尚不清楚,其生物学治疗仍处于动物实验研究阶段,只有通过大量的临床样本及动物试验,并探求出更加深入细致的研究方法,尤其是最热点及最有前途的组织工程方法,才能为在最终应用于人椎间盘退行性变的治疗上提供切实可靠的治疗手段。     

Transforming growth factor beta-1 signalling in canine hepatic diseases: new models for human fibrotic liver pathologies.

BACKGROUND/AIMS: The purpose of this study was to validate spontaneous chronic hepatitis and cirrhosis in dogs as a potential large animal model for fibrotic liver disease in humans by evaluating their molecular pathophysiology. METHODS: Transforming growth factor-beta1 (TGF-beta1) signalling was analysed in liver samples of dogs with acute hepatitis (AH), chronic hepatitis (CH), cirrhosis (CIRR), and a specific form of cirrhosis, lobular dissecting hepatitis (LDH), in comparison with human cirrhotic samples from alcohol abuse (ALC) and hepatitis C (HC). RESULTS: Canine samples were investigated with quantitative real-time PCR (Q-PCR) and Western blotting on TGF-beta1 signalling including Smad2/3 phosphorylation. Immunohistochemistry on collagens I and III was performed. Q-PCR showed an increase in TGF-beta1 levels and downstream effector gene products in CH, LDH, and CIRR. The same fibrotic diseases also showed an increase in phosphorylated Smad2/3 and a higher deposition of collagens I and III. In contrast, in AH neither active TGF-beta1 signalling nor collagen deposition was observed. Western blot analysis on human ALC and HC indicated a high similarity with canine samples in TGF-beta1 expression and Smad2/3 phosphorylation. CONCLUSIONS: Our results demonstrate that fibrosis in spontaneous dog liver diseases is highly comparable to their human counterparts and might serve as models for anti-fibrotic strategies.     

Acute choke zone effects: Lessons from radioactive and fluorescent microspheres in a pig model muscle flap

BACKGROUND:

Choke vessels dilate and contract to regulate blood flow between adjacent arterial angiosomes. In skin flap surgery, when arterial inflow to an angiosome is ligated, choke vessels allow blood supply from an adjacent angiosome. In muscle flap surgery, the vascular anatomy is analogous to skin flaps; however, while it is established that the choke vessels will fully dilate irreversibly after two to three days, no study has yet analyzed the acute changes in each vascular region immediately following ligation of one pedicle.

OBJECTIVE:

To establish whether the choke vessels open or close immediately following ligation of a pedicle, and how this change affects blood flow in the adjacent proximal and distal vascular regions.

METHODS:

Radioactive and fluorescent microspheres in a pig model were used to study the regional intramuscular blood flow in each anatomical zone of a rectus abdominis flap. Blood flow measurements for each zone were calculated relative to the entire muscle at preligation, ligation and various times (15 min to 90 min) postligation.

RESULTS:

There was no statistically significant difference in blood flow across choke zones as a result of ligation. This signifies that the choke vessels do not significantly dilate to produce a statistically significant measureable change in blood flow.

CONCLUSIONS:

Given these results and previous literature findings, the anatomical presence of choke vessels in a muscle is the strongest determining factor for acute flap viability in surgery.