反应停治疗难治性多发性骨髓瘤25例

1临床资料我院2001-02/2004-01接受2个疗程卡氮芥 环磷酰胺 马法兰 泼尼松 长春新碱或2个疗程长春新碱 阿霉素 地塞米松方案化疗无效或复发的难治性多发性骨髓瘤患者25(男16,女9)例,年龄42～80(中位年龄57.2)岁.单用反应停口服治疗,起始剂量200 mg/d,如无不良反应,每周增加100 mg,根据患者耐受情况,最高剂量为600 mg/d,3 mo为1疗程.服药期间禁止使用糖皮质激素类药物及细胞毒药物.     

Hyperinsulinism of infancy: the regulated release of insulin by KATP channel-independent pathways

Hyperinsulinism of infancy (HI) is a congenital defect in the regulated release of insulin from pancreatic beta-cells. Here we describe stimulus-secretion coupling mechanisms in beta-cells and intact islets of Langerhans isolated from three patients with a novel SUR1 gene defect. 2154+3 A to G SUR1 (GenBank accession number L78207) is the first report of familial HI among nonconsanguineous Caucasians identified in the U.K. Using patch-clamp methodologies, we have shown that this mutation is associated with both a decrease in the number of operational ATP-sensitive K+ channels (KATP channels) in beta-cells and impaired ADP-dependent regulation. There were no apparent defects in the regulation of Ca2+- and voltage-gated K+ channels or delayed rectifier K+ channels. Intact HI beta-cells were spontaneously electrically active and generating Ca2+ action currents that were largely insensitive to diazoxide and somatostatin. As a consequence, when intact HI islets were challenged with glucose and tolbutamide, there was no rise in intracellular free calcium ion concentration ([Ca2+]i) over basal values. Capacitance measurements used to monitor exocytosis in control and HI beta-cells revealed that there were no defects in Ca2+-dependent exocytotic events. Finally, insulin release studies documented that whereas tolbutamide failed to cause insulin secretion as a consequence of impaired [Ca2+]i signaling, glucose readily promoted insulin release. Glucose was also found to augment the actions of protein kinase C- and protein kinase A-dependent agonists in the absence of extracellular Ca2+. These findings document the relationship between SUR1 gene defects and insulin secretion in vivo and in vitro and describe for the first time KATP channel-independent pathways of regulated insulin secretion in diseased human beta-cells.     

Practical management of hyperinsulinism in infancy

Hyperinsulinism in infancy is one of the most difficult problems to manage in contemporary paediatric endocrinology. Although the diagnosis can usually be achieved without difficulty, it presents the paediatrician with formidable day to day management problems. Despite recent advances in understanding the pathophysiology of hyperinsulinism, the neurological outcome remains poor, and there is often a choice of unsatisfactory treatments, with life long sequelae for the child and his or her family. This paper presents a state of the art overview on management derived from a consensus workshop held by the European network for research into hyperinsulinism (ENRHI). The consensus is presented as an educational aid for paediatricians and children's nurses. It offers a practical guide to management based on the most up to date knowledge. It presents a proposed management cascade and focuses on the clinical recognition of the disease, the immediate steps that should be taken to stabilise the infant during diagnostic investigations, and the principles of definitive treatment.     

Nurses' perceived barriers to the implementation of a Fall Prevention Clinical Practice Guideline in Singapore hospitals

Background  

Theories of behavior change indicate that an analysis of barriers to change is helpful when trying to influence professional practice. The aim of this study was to assess the perceived barriers to practice change by eliciting nurses' opinions with regard to barriers to, and facilitators of, implementation of a Fall Prevention clinical practice guideline in five acute care hospitals in Singapore.     

Ionic control of beta cell function in nesidioblastosis. A possible therapeutic role for calcium channel blockade.

A preterm female infant presented with intractable hypoglycaemia within 10 minutes of delivery. Normoglycaemia could be maintained only by the intravenous infusion of glucose at a rate of 20-22 mg/kg/min. Persistent hyperinsulinaemic hypoglycaemia of infancy was diagnosed from an inappropriately raised plasma insulin concentration (33 mU/l) at the time of hypoglycaemia (blood glucose < 0.5 mmol/l). Medical treatment with glucagon, somatostatin, and diazoxide led to only a modest reduction in the intravenous glucose requirement; a 95% pancreatectomy was performed and histological ''nesidioblastosis'' confirmed. In vitro electrophysiological studies using patch clamp techniques on isolated pancreatic beta cells characterised the ionic basis for insulin secretion in nesidioblastosis. The beta cells were depolarised in low ambient glucose concentrations with persistently firing action potentials; these were blocked reversibly by the calcium channel blocking agent verapamil. Persistent postoperative hyperinsulinaemic hypoglycaemia was treated with oral nifedipine. This increased median blood glucose concentrations from 3.5 to 4.8 mmol/l and increased in duration the child''s tolerance to fasting from 3 to 10.5 hours. These data allude to an abnormality in the ionic control of insulin release in nesidioblastosis and offer a new logical approach to treatment which requires further evaluation.