吗啡受体显像剂7α-o-IA-DPN的合成

设计、合成了一种新的吗啡受体显像剂。选用吗啡拮抗剂特培洛啡（ｄｉｐｒｅｎｏｒｐｈｉｎｅ，ＤＰＮ），经乙酰化选择性保护苯环３位—ＯＨ，将乙烯锡烷作为弥补基引入ＤＰＮ分子７α支链淑醇基团位置，采用碘代锡烷标记法一步合成碘烷ＤＰＮ（７αｏｉｏｄｏａｌｙｌｄｉｐｒｅｎｏｒｐｈｉｎｅ，即７αｏＩＡＤＰＮ）。其标记率达９０％，比活度为８０ＴＢｑ／ｍｍｏｌ，放化纯度大于９５％。体外吗啡受体结合分析表明其具有很高的亲和力（Ｋｉ＝０．４ｎｍｏｌ／Ｌ）。结果表明：新合成的碘标记吗啡配体适合于ＳＰＥＣＴ活体吗啡受体显像研究。     

Primary central nervous system immunocytoma: MRI and spectroscopy

We report on a young woman with a primary cerebral immunocytoma. Most primary cerebral nervous system lymphomas (PCNSL) are highly malignant undifferentiated B-cell tumours, there are few data on the clinical course, MRI and spectroscopy findings of this rare PCNSL subtype. MRI revealed a radially enhancing tumour with mild perifocal oedema. MR spectroscopy indicated low cell turnover. Slow clinical progression, no significant changes with treatment, and imaging findings were consistent with a low-grade malignant tumour. Received: 21 January 2000/Accepted: 15 February 2000     

Analysis of cDNA sequences of feline SAAs

Feline amyloidosis is an uncommon disorder caused by deposits of amyloid in a variety of organs. Most frequently encountered types are amyloid derived of pancreatic islet amyloid polypeptide (AIAPP) in older cats and of the apolipoprotein, apo-serum amyloid A (AA) in Abyssinian/Somali (Aby) and Siamese/Oriental (Siam) cats occurring at a relatively young age. For the AA protein of the Aby, Siam and domestic shorthair cat (DSH) breed different amino acid sequences have been described. It is not yet clear, however, whether the tendency to develop AA amyloidosis in Aby and Siam is associated with specific apoSAA protein sequences and whether this is breed specific. In this study, DNA from one Siam and two DSH cats revealed on Southern blot three bands suggesting at least three genes or gene clusters. The SAA cDNAs of hepatic mRNA from three Abys, five Siams and five DSHs were amplified by RT-PCR, cloned and sequenced. Siams and Abys had limited SAA sequence variability. All five Siams, three of which were positive for amyloid, had the amyloidogenic Siam SAA and the amyloidogenic Aby SAA sequence. Two of the Abys, both with amyloid, had the amyloidogenic Aby SAA sequence. The third Aby, without amyloid, missed its amyloidogenic sequence. The SAA sequences of the DSHs found in the present preliminary survey, suggested a possible tendency for more variability, whereas the amyloidogenic Siam as well as the amyloidogenic Aby sequence were found once. Up to five different sequences were found in a single animal. All five DSHs, moreover, had a specific sequence lacking in the Siams and Abys. The present results, especially those of the Siams, favor that in addition to the occurrence of amyloid associated SAA genes other factors such as infections and inflammatory processes are involved in the development of phenotypical amyloidosis.     

Retention of the posterior cruciate ligament versus the posterior stabilized design in total knee arthroplasty: a prospective randomized controlled clinical trial

Background  

Prosthetic design for the use in primary total knee arthroplasty has evolved into designs that preserve the posterior cruciate ligament (PCL) and those in which the ligament is routinely sacrificed (posterior stabilized). In patients with a functional PCL the decision which design is chosen depends largely on the favour and training of the surgeon.     

Incorporating and evaluating an integrated gender-specific medicine curriculum: a survey study in Dutch GP training

Background  

We recently set standards for gender-specific medicine training as an integrated part of the GP training curriculum. This paper describes the programme and evaluation of this training.     

Are faecal markers good indicators of mucosal healing in inflammatory bowel disease?

AIM: To review the published literature concerning the accuracy of faecal inflammatory markers for identifying mucosal healing. METHODS: Bibliographical searches were performed in MEDLINE electronic database up to February 2015,using the following terms: "inflammatory bowel disease","Crohn′s disease","ulcerative colitis","faecal markers","calprotectin","lactoferrin","S100A12","endoscop*","mucosal healing","remission". In addition,relevant references from these studies were also included. Data were extracted from the published papers including odds ratios with 95%CI,P values and correlation coefficients. Data were grouped together according to each faecal marker,Crohn's disease or ulcerative colitis,and paediatric compared with adult study populations. Studies included in this review assessed mucosal inflammation by endoscopic and/or histological means and compared these findings to faecal marker concentrations in inflammatory bowel diseases(IBD) patient cohorts. Articles had to be published between 1990 and February 2015 and written in English. Papers excluded from the review were those where the faecal biomarker concentration was compared between patients with IBD and controls or other disease groups,those where serum biomarkers were used,those with a heterogeneous study population and those only assessing post-operative disease. RESULTS: The available studies show that faecal markers,such as calprotectin and lactoferrin,are promising non-invasive indicators of mucosal healing. However,due to wide variability in study design,especially with regard to the definition of mucosal healing and evaluation of marker cut offs,the available data do not yet indicate the optimal roles of these markers. Thirty-six studies published between 1990 and 2014 were included. Studies comprised variable numbers of study participants,considered CD(15-164 participants) or UC(12-152 participants) separately or as a combined group(11-252 participants). Eight reports included paediatric patients. Several indices were used to document mucosal inflammation,encompassing elevenendoscopic and eight histologic grading systems. The majority of the available reports focused on faecal calprotectin(33 studies),whilst others assessed faecal lactoferrin(13 studies) and one study assessed S100A12. Across all of the biomarkers,there is a wide range of correlation describing the association between faecal markers and endoscopic disease activity(r values ranging from 0.32 to 0.87,P values ranging from 0.0001 to 0.7815). Correlation coefficients are described in almost all studies and are used more commonly than outcome measures such as sensitivity,specificity,PPV and/or NPV. Overall,the studies that have evaluated faecal calprotectin and/or faecal lactoferrin and their relationship with endoscopic disease activity show inconsistent results. CONCLUSION: Future studies should report the results of faecal inflammatory markers in the context of mucosal healing with clear validated cut offs.     

Large head metal-on-metal cementless total hip arthroplasty versus 28mm metal-on-polyethylene cementless total hip arthroplasty: design of a randomized controlled trial

Background  

Osteoarthritis of the hip is successfully treated by total hip arthroplasty with metal-on-polyethylene articulation. Polyethylene wear debris can however lead to osteolysis, aseptic loosening and failure of the implant. Large head metal-on-metal total hip arthroplasty may overcome polyethylene wear induced prosthetic failure, but can increase systemic cobalt and chromium ion concentrations. The objective of this study is to compare two cementless total hip arthroplasties: a conventional 28 mm metal-on-polyethylene articulation and a large head metal-on-metal articulation. We hypothesize that the latter arthroplasties show less bone density loss and higher serum metal ion concentrations. We expect equal functional scores, greater range of motion, fewer dislocations, fewer periprosthetic radiolucencies and increased prosthetic survival with the metal-on-metal articulation.     

7α-O-IA-DPN:特异性碘标记阿片配体的研制和评价

目的：研制和评价新碘标阿片受体显像剂７αＯｉｏｄｏａｌｙｌｄｉｐｒｅｎｏｒｐｈｉｎｅ（７αＯＩＡＤＰＮ）。方法：选用阿片肽拮抗剂ＤＰＮ经碘代锡烷标记法成功地获得了一个原始的碘标阿片肽类似物，并对其进行理化性能、药理作用和生物学功能评价。结果：体外和体内阿片受体结合分析表明这一新的阿片配体具有非常高的亲和力（Ｋｉ＝４×１０－４μｍｏｌ／Ｌ）。注药后２０ｍｉｎ动物脑内的特异性结合占６３％，且其在脑内滞留时间较长而有利于成像。阿片抑制试验和抗痛活性研究分别反映碘标７αＯＩＡＤＰＮ可能对３种阿片受体（μ，δ，κ）都有亲和力，并保持了原有的药理特性和生物学功能。结论：碘标７αＯＩＡＤＰＮ作为新阿片受体显像剂较适于今后ＳＰＥＣＴ阿片受体研究。