Elevated plasma adiponectin in humans with genetically defective insulin receptors

CONTEXT: Adiponectin has been suggested to play a role in the etiopathogenesis of at least some forms of insulin resistance, in part based on a strong correlation between plasma levels of adiponectin and measures of insulin sensitivity. OBJECTIVE: The objective of the study was to establish whether this relationship is maintained at extreme levels of insulin resistance. DESIGN/SETTING: This was a cross-sectional study in a university teaching hospital of subjects recruited from the United Kingdom and the United States. PARTICIPANTS: Participants included 75 subjects with a range of syndromes of severe insulin resistance and 872 nondiabetic controls. OUTCOME MEASURES: Fasting plasma insulin, adiponectin, and leptin were measured. RESULTS: Unexpectedly, subjects with mutations in the insulin receptor, despite having the most severe degree of insulin resistance, had elevated plasma adiponectin [median 24.4 mg/liter; range 6.6-36.6 (normal adult range for body mass index 20 kg/m(2) = 3-19 mg/liter)], whereas all other subjects had low adiponectin levels (median 2.0 mg/liter; range 0.12-11.2). Plasma leptin in all but one subject with an insulin receptoropathy was low or undetectable [median 0.5 ng/ml; range 0-16: normal adult range for body mass index of < 25 kg/m(2) = 2.4-24.4 (female) and 0.4-8.3 ng/ml (male)]. CONCLUSIONS: We conclude that the relationship between plasma adiponectin and insulin sensitivity is complex and dependent on the precise etiology of defective insulin action and that the combination of high plasma adiponectin with low leptin may have clinical utility in patients with severe insulin resistance as a marker of the presence of a genetic defect in the insulin receptor.     

Interviewing one's peers: methodological issues in a study of health professionals

OBJECTIVE: Although health professionals are increasingly undertaking qualitative interviews with professional peers, there is little literature regarding the methodological implications of this process. The aim of the study was to elicit from informants their views on being interviewed by a fellow health professional. DESIGN: Semi-structured interviews with nine general practitioners (GPs), three rheumatologists, and three physical therapists, with a substantive focus on perceptions of osteoarthritis. The interviewer was a GP, and informants were asked for their reactions to being interviewed by a fellow professional. Data were analysed by hand, using a thematic approach. SETTING: Primary care clinics and practices in the UK. RESULTS: Although reassured to the contrary, many informants viewed the interview as a test of their professional knowledge. The interview was also seen by some GPs as serving an educational process, with the interviewer as an authoritative source of clinical information. There were some indications of professional vulnerability among informants in relation to possible scrutiny of their practice or knowledge, though none reported a negative experience of the interview. Notions of professional identity appeared central to many of the issues that emerged. CONCLUSION: The nature of the relationship in interviews involving professional peers creates specific methodological issues, which have important implications for qualitative research in primary healthcare. There are both advantages and disadvantages to interviewing professional peers, which should be considered in the light of the objectives of a particular study.     

Primary effusion lymphoma: genomic profiling revealed amplification of SELPLG and CORO1C encoding for proteins important for cell migration

Primary effusion lymphoma (PEL) is associated with Kaposi sarcoma herpesvirus (KSHV) but its pathogenesis is poorly understood. Many KSHV‐associated products can deregulate cellular pathways commonly targeted in cancer. However, KSHV infection alone is insufficient for malignant transformation. PEL also lacks the chromosomal translocations seen in other lymphoma subtypes. We investigated 28 PELs and ten PEL cell lines by 1 Mb resolution array comparative genomic hybridization (CGH) and found frequent gains of 1q21–41 (47%), 4q28.3‐35 (29%), 7q (58%), 8q (63%), 11 (32%), 12 (61%), 17q (29%), 19p (34%), and 20q (34%), and losses of 4q (32%), 11q25 (29%), and 14q32 (63%). Recurrent focal amplification was seen at several regions on chromosomes 7, 8, and 12. High‐resolution chromosome‐specific tile‐path array CGH confirmed these findings, and identified selectin‐P ligand (SELPLG) and coronin‐1C (CORO1C) as the targets of a cryptic amplification at 12q24.11. Interphase FISH and quantitative PCR showed SELPLG/CORO1C amplification (>4 extra copies) and low levels of copy number gain (1–4 extra copies) in 23% of PELs, respectively. Immunohistochemistry revealed strong expression of both SELPLG and coronin‐1C in the majority of PELs, irrespective of their gene dosage. SELPLG is critical for cell migration and chemotaxis, while CORO1C regulates actin‐dependent processes, thus important for cell motility. Their overexpression in PEL is expected to play an important role in its pathogenesis. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Continuous intensity map optimization (CIMO): a novel approach to leaf sequencing in step and shoot IMRT

A new leaf-sequencing approach has been developed that is designed to reduce the number of required beam segments for step-and-shoot intensity modulated radiation therapy (IMRT). This approach to leaf sequencing is called continuous-intensity-map-optimization (CIMO). Using a simulated annealing algorithm, CIMO seeks to minimize differences between the optimized and sequenced intensity maps. Two distinguishing features of the CIMO algorithm are (1) CIMO does not require that each optimized intensity map be clustered into discrete levels and (2) CIMO is not rule-based but rather simultaneously optimizes both the aperture shapes and weights. To test the CIMO algorithm, ten IMRT patient cases were selected (four head-and-neck, two pancreas, two prostate, one brain, and one pelvis). For each case, the optimized intensity maps were extracted from the Pinnacle3 treatment planning system. The CIMO algorithm was applied, and the optimized aperture shapes and weights were loaded back into Pinnacle. A final dose calculation was performed using Pinnacle's convolution/superposition based dose calculation. On average, the CIMO algorithm provided a 54% reduction in the number of beam segments as compared with Pinnacle's leaf sequencer. The plans sequenced using the CIMO algorithm also provided improved target dose uniformity and a reduced discrepancy between the optimized and sequenced intensity maps. For ten clinical intensity maps, comparisons were performed between the CIMO algorithm and the power-of-two reduction algorithm of Xia and Verhey [Med. Phys. 25(8), 1424-1434 (1998)]. When the constraints of a Varian Millennium multileaf collimator were applied, the CIMO algorithm resulted in a 26% reduction in the number of segments. For an Elekta multileaf collimator, the CIMO algorithm resulted in a 67% reduction in the number of segments. An average leaf sequencing time of less than one minute per beam was observed.     

双入路法在腹腔镜下游离结肠脾曲的直肠癌保肛术中的应用

目的总结腹腔镜双入路法在游离脾曲的直肠癌保肛术的操作经验及应用价值。 方法回顾分析2016年4月至2017年9月由同一组手术医师完成的双入路法腹腔镜下游离结肠脾曲的直肠癌保肛手术38例患者的临床资料及短期随访结果。 结果所有手术均获成功,无中转开腹病例,术中无左侧输尿管、左肾、脾脏及胰腺损伤。手术时间为142.4±35.3 min,术中出血量98.7±34.5 ml,切除标本长度为21.1±6.7 cm,肿瘤距下切缘4.5±2.8 cm,清除淋巴结为12.7±6.3枚,术后排气时间3.6±1.7 d,住院时间12.4±3.2 d。术后并发症4例（10.5%）,其中切口感染2例（5.26%）,尿潴留1例（2.63%）,肺部感染1例（2.63%）,无吻合口漏、吻合口出血等并发症发生。全组患者随访至今,均未见肿瘤复发。 结论双入路法在腹腔镜下游离结肠脾曲的直肠癌保肛术中径路准确,解剖层面清晰、易于掌握,值得推广应用。     

The study of exercise tests in paroxysmal kinesigenic dyskinesia

Objective

To unravel if there was muscular ion channel dysfunction in paroxysmal kinesigenic dyskinesia (PKD) patients using the exercises tests (ET).

护生职业防护认知及培训需求调查

[目的]了解实习护生对职业防护知识的认知程度和培训需求,为开展系统的临床职业防护教育提供依据.[方法]采用自行设计的调查问卷对200名实习护生进行调查.[结果]不同学历护生对职业伤害定义、物理性职业伤害、化学性职业伤害知识和常见职业伤害的认知存在统计学差异(P<0.05).84.8%的本科护生和70.7%的大专护生表示对医院职业防护相关规定不了解.[结论]实习护生职业防护认知度及需求存在差异,职业防护培训仍需要进一步加强,学校和医院应当通过系统的职业防护教育,增强护生的职业防护意识,提高职业防护能力.     

高糖体外对视网膜色素上皮增生以及活性氧表达的影响

目的:研究高浓度葡萄糖对体外培养的视网膜色素上皮(retinal pigment epithelium,RPE)细胞增生以及活性氧(reactive oxygen species,ROS)生成的影响。方法:体外培养人RPE(ARPE-19),随机分成4组,即正常对照组用含5.6mmol/L葡萄糖的DMEM/F12培养液,高糖组用30mmol/L葡萄糖的DMEM/F12培养液,高糖+SB203580组用p38-MAPK特异性阻断剂SB20358010μmol/L预处理30min后,再用含30mmol/L葡萄糖的DMEM/F12培养液,甘露醇组(渗透压对照组)用含5.6mmol/L葡萄糖和24.4mmol/L甘露醇的DMEM/F12培养液。各组培养48h用MTT法检测各组视网膜色素上皮细胞的增生活力,用CM-H2DCFDA荧光染色检测RPE细胞中ROS的产生量。结果:与对照组相比,高糖培养人视网膜色素上皮细胞48h可以导致RPE细胞的损伤,抑制RPE细胞增殖,并使ROS生成增加,在一定程度上,与p38-MAPK途径的激活有关。结论:高糖培养ARPE-19可致细胞损伤,抑制增殖,并使ROS生成增加。