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。     

Intravenous pulse methylprednisolone therapy of acute crescentic rapidly progressive glomerulonephritis.

Idiopathic acute crescentic rapidly progressive glomerulonephritis (RPGN) with oliguria, proteinuria and rapid decline of renal function is usually associated with death or the need for support by dialysis. Spontaneous recovery is rare, and various modes of therapy have been generally unsuccessful.We describe nine patients with rapidly progressive glomerulonephritis of less than six weeks' duration whose creatinine clearance decreased over 50 per cent. All had normal-sized kidneys and were proteinuric, six of nine were oliguric, and five of nine required dialysis. Renal biopsy specimens were examined by light, electron and immunofluorescence microscopy. Rapidly progressive glomerulonephritis without immune deposits was present in six, immune complex disease in two and antiglomerular basement membrane disease in one. All were treated with intravenous pulse methylprednisolone followed by oral steroids. Serum creatinines decreased in seven of nine patients from one to four weeks after pulse therapy and remained stable or improved in six of these. Three of five patients undergoing dialysis were able to discontinue that support. The mean creatinines of 10.6 ± 2.2 mg/dl before therapy decreased to 2.2 ± 0.5 mg/dl after four to 24 months in the six responding patients. Two other patients died of causes unrelated to therapy. Tissue obtained from four patients four to 12 months after pulse therapy showed resolution of inflammatory changes and regression of crescents.The marked and sustained improvement of renal function in six of our nine (67 per cent) patients with rapidly progressive glomerulonephritis who were treated with pulse methylprednisolone is in sharp contrast to experience previously reported and suggests the need for further evaluation in a prospective controlled study.     

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.     

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.     

Do androgens enhance the response to antithymocyte globulin in patients with aplastic anemia? A prospective randomized trial

We analyzed the effect of antithymocyte globulin (ATG) with or without androgens in 121 patients with aplastic anemia. Fifty-three patients with moderate to severe aplastic anemia were prospectively randomized to receive ATG with or without oral androgens. Eleven of 26 patients (42%) receiving ATG plus androgen responded, including three complete and eight partial responses. Twelve of 27 patients (44%) receiving ATG plus placebo responded, including five complete and seven partial responses. The difference in response rates was not significant (P greater than .9). Survival was also comparable in the two groups; for patients with severe aplastic anemia, actuarial survival at two years was 55% +/- 24% (95% confidence interval) in patients receiving ATG plus androgen compared with 50% +/- 24% in the ATG plus placebo group (P = .65). Furthermore, results in both groups were indistinguishable from those obtained in 68 historical controls receiving ATG without androgens. These data indicate that androgens are not required in order to respond to antithymocyte globulin and the addition of androgens, as used in this trial, did not significantly improve response rates to ATG treatment.     

Wait times for gastroenterology consultation in Canada: The patients�� perspective

Long wait times for health care have become a significant issue in Canada. As part of the Canadian Association of Gastroenterology’s Human Resource initiative, a questionnaire was developed to survey patients regarding wait times for initial gastroenterology consultation and its impact. A total of 916 patients in six cities from across Canada completed the questionnaire at the time of initial consultation. Self-reported wait times varied widely, with 26.8% of respondents reporting waiting less than two weeks, 52.4% less than one month, 77.1% less than three months, 12.5% reported waiting longer than six months and 3.6% longer than one year. One-third of patients believed their wait time was too long, with 9% rating their wait time as ‘far too long’; 96.4% believed that maximal wait time should be less than three months, 78.9% believed it should be less than one month and 40.3% believed it should be less than two weeks. Of those working or attending school, 22.6% reported missing at least one day of work or school because of their symptoms in the month before their appointment, and 9.0% reported missing five or more days in the preceding month. A total of 20.2% of respondents reported being very worried about having a serious disease (ie, scored 6 or higher on 7-point Likert scale), and 17.6% and 14.8%, respectively, reported that their symptoms caused major impairment of social functioning and with the activities of daily living. These data suggest that a significant proportion of Canadians with digestive problems are not satisfied with their wait time for gastroenterology consultation. Furthermore, while awaiting consultation, many patients experience an impaired quality of life because of their gastrointestinal symptoms.     

Carcinoma of endocrine organs: results of the RARECARE project

The rarity or the asymptomatic character of endocrine tumours results in a lack of epidemiological studies on their incidence and survival patterns. The aim of this study was to describe the incidence, prevalence and survival of endocrine tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002, registered in 89 population-based cancer registries (CRs) with follow-up until 31st December 2003. These data give an unique overview of the burden of endocrine carcinomas in Europe. A list of tumour entities based on the third International Classification of Diseases for Oncology was provided by the project Surveillance of rare cancer in Europe (RARECARE) project. Over 33,594 cases of endocrine carcinomas were analysed in this study. Incidence rates increased with age and were highest in patients 65 years of age or older. In 2003, more than 315,000 persons in the EU (27 countries) were alive with a past diagnosis of a carcinoma of endocrine organs. The incidence of pituitary carcinoma equalled four per 1,000,000 person years and showed the strongest decline in survival with increasing age. Thyroid cancer showed the highest crude incidence rates (four per 100,000 person years) and was the only entity with a gender difference: (female-to-male ratio: 2:9). Parathyroid carcinoma was the rarest endocrine entity with two new cases per 10,000,000 person years. For adrenal carcinoma, the most remarkable observations were a higher survival for women compared to men (40% compared to 32%, respectively) and a particularly low relative survival of 24% in patients 65 years of age or older. More high quality studies on rare cancers, with additional information, e.g. on stage and therapeutic approach, are needed and may be of help in partly explaining the observed variation in survival.