Influence of cholecystokinin on insulin output from isolated perifused pancreatic islets

The C-terminal eight-amino acid derivative of CCK, sulfated on the tyrosine residue (CCK8S), stimulated a dose-dependent biphasic pattern of insulin secretion from isolated perifused islets in the presence of 7 mM glucose. It was without any effect if glucose were absent from the medium or maintained at 4 mM. The response to CCK8S was readily reversible and dependent on the presence of extracellular calcium. While CCK8S did not increase glucose usage rates above those noted with 7 mM glucose alone, inclusion of the metabolic inhibitor 2-deoxyglucose lowered glucose usage rates to values obtained with 3-5 mM glucose and abolished the influence of CCK8S on insulin output. Removal of the metabolic inhibitor restored the secretory response. N-Acetylglucosamine (15 mM) or glyceraldehyde (2.5 mM) substituted for glucose and permitted CCK8S to evoke secretion. The nonsulfated eight-amino acid derivative of CCK, CCK8, provoked insulin secretion in the presence of 7 mM glucose, but only at 10-100 times greater levels than CCK8S. CCK4 (1 microM) did not influence insulin output in the presence of 7 mM glucose. On an equimolar basis, CCK8S was significantly more effective than gastric inhibiting polypeptide in augmenting insulin output. The results support a role for CCK8S in the regulation of insulin levels in vivo.     

Time-dependent effects of cholinergic stimulation on beta cell responsiveness

The effects of cholinergic stimulation on beta cell insulin secretory and phosphoinositide (PI) responses were determined in freshly isolated rat islets. Increasing the glucose level perifusing the islet from 5.6 to 8mM was accompanied by a modest insulin secretory response. The further addition of 10 μM carbachol increased peak first- and second-phase responses by 2.6- and 6.8-fold, respectively. In the presence of 5.6 mM glucose, this low level (10 μM) of carbachol increased insulin release two- to three-fold, a response that was maintained for at least 60 min. In contrast to these acute stimulatory actions in the presence of glucose, chronic 3.5-h exposure of islets to 10 μM carbachol abolished beta cell insulin secretory responses to stimulation, with the combination of 8 mM glucose plus 10 μM carbachol. However, the further addition of 200 μM tolbutamide to these islets increased insulin secretory rates significantly. To establish the role of islet cell PI hydrolysis in these secretory responses, additional studies were conducted with islets whose PI pools were labeled with [³H]inositol. Acute exposure to 10 μM carbachol alone significantly increased inositol phosphate accumulation and the efflux of [³H]inositol, even in the absence of glucose. Including 10 μM carbachol during the labeling period with [³H]inositol resulted in significant impairments in subsequently measured inositol phosphate accumulation and [³H]inositol efflux responses to 8 mM glucose plus carbachol stimulation. Prior long-term exposure to 10 μM carbachol also induced heterologous desensitization: 20 mM glucose-stimulated insulin release and inositol phosphate accumulation were impaired in a parallel fashion. Chronic carbachol exposure had no deleterious effect on the usage of 8 or 20 mM glucose or on the insulin content of the islet. The acute stimulatory effects of carbachol on inositol phosphate accumulation as well as its inhibitory effect on 20 mM glucose-stimulated insulin release after prolonged exposure to the muscarinic agonist were significantly reduced by atropine. These findings demonstrate that changes in PI hydrolysis parallel those observed with insulin secretion and suggest that alterations in phospholipase C activation may account, at least in part, for the insulin secretory responses observed. Received: 31 July 1995/Received after revision: 9 February 1996/Accepted: 11 March 1996     

Thymic teratoma masquerading as a thyroid lump

Teratomas are germ cell tumours commonly found in the sacrococcygeal region, ovary, testicle or, infrequently, the mediastinum. In very rare circumstances, these tumours are found in the neck. This case represents a thymic teratoma presenting as what appeared to be an intrathyroid lesion. This has not been described previously and demonstrates an unusual presentation of a neck lump necessitating two operations and a multidisciplinary approach for management. We would also like to highlight that while patients undergo imaging to guide surgery, the surgeon must always be prepared for the unexpected and recognise situations where the operation should be converted to an exploratory procedure instead of full resection. Often, combined surgical care is the best option for difficult congenital cases.     

QUADAS评价:一种用于诊断性研究的质量评价工具(修订版)

背景 QUADAS是一种新近发展起来的诊断性研究的质量评价工具。虽然已有系统评价采用了QUADAS,但尚未得以正式确证。本研究的目的是评价QUADAS的有效性和实用性。方法3位评价者采用QUADAS独立评价30项研究的质量。比较每位评价者的评分与最终结论之间的意见一致度。这主要是通过比较所有QUADAS条目的总分和每个单项的得分来实现的。20位曾在其系统评价中使用过QUADAS的评价者就其使用经验完成一份简短的问卷。结果就所有条目而言,每位评价者的评分与最终结论之间的意见一致度分别达到了91%、90%和85%。就单项QUADAS条目而言,一致度在50%至100%之间,中位值是90%。与难以解释的试验结果和退出病例相关的条目,评分结果差异最大。有关QUADAS内容的反馈意见普遍较好,仅少数评价者提出了有关QUADAS涵盖面、使用便利性、评分说明的清晰度及有效性方面的问题。结论QUADAS内容本身无需作大的修改。评价过程的主要困难出现在难以解释的试验结果和退出病例这2个条目的评分上。对这些条目的评分指南提出了修改意见。评价者必需根据其系统评价制定相应的评分指南,并确保所有评价者都清楚如何评分。评价者还应考虑是否所有的QUADAS条目都与其系统评价相关,以及其他质量条目是否应作为其系统评价的评价部分。     

QUADAS的制定:用于系统评价中评价诊断性研究质量的工具

背景在以系统评价为基石的循证医学时代,需要有恰当的质量评价工具。对诊断性研究的评价目前尚缺乏系统开发且经过验证的评价工具。本研究的目的是采用共识决策法整合经验证据和专家意见,制定在系统评价时用于评价原始诊断性研究质量的工具。方法按照循证原则,我们在之前发表的3篇诊断性研究文献的综述的基础上,初选出一些条目形成列表,然后通过Delphi流程逐步调整列表,形成质量评价工具。参与Delphi流程的都是诊断性研究领域的专家。结果共有9位诊断学领域的专家参与Delphi流程。经过4轮Delphi流程后,专家们对哪些条目应纳入评价工具达成共识,我们把这个评价工具命名为QUADAS。纳入条目从最初的28个减少到14个,涵盖了疾病谱、金标准、疾病进展偏倚(disease progression bias)、证实偏倚(verification bias)、评价偏倚、临床评价偏倚、合并偏倚、试验的实施、病例退出以及不确定结果。QUADAS工具中的每个条目都配有评分细则。结论本研究项目开发出了用于诊断性试验系统评价的循证质量评价工具。下一步工作是确定其适用性和有效性。     

Glycoproteins present in human follicular fluid that inhibit the zona- binding capacity of spermatozoa

Previous studies have suggested that human follicular fluid contains factors that reduce the zona-binding capacity of spermatozoa. The present study provides further evidence of the existence of such factors. Using the hemizona binding assay (HZA), we have shown that the inhibitory effect of human follicular fluid on the zona-binding capacity of spermatozoa is concentration-dependent, an inhibitory effect being detected when the concentration of human follicular fluid was > or = 10%. A 1% concentration of human follicular fluid did not possess this inhibitory activity. Heating human follicular fluid at 56 degrees C for 30 min did not affect its inhibitory properties; treatment with proteinase-K abolished such inhibition. Human follicular fluid was fractionated sequentially by concanavalin-A affinity chromatography, Mono Q ion-exchange chromatography and Superose-12 gel filtration. The zona binding inhibitory activity resided in the fraction which bound to the lectin and Mono Q column and contained molecules with native molecular weights of 32 and 192 kDa. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis suggested that the 192 kDa glycoprotein was a tetramer, while the 32 kDa glycoprotein remained as a single molecular species under denaturing conditions. We conclude that two glycoproteins were responsible for the zona binding inhibitory activity of human follicular fluid. The physiological role of these factors remains unclear.