Iridium‐mediated β‐deuteration of enones

Exposure of captodative enone systems to deuterium in the presence of Crabtree's catalyst ( 1 ) results in deuteration at the vinylic site β‐ to the ketone carbonyl, as well as at any accessible ortho‐position. β‐exchange is also observed during the reduction of ethyl cinnamate ( 3 ) catalyzed by 1 . Copyright © 2003 John Wiley & Sons, Ltd.     

Fisher information matrix for nonlinear mixed effects multiple response models: Evaluation of the appropriateness of the first order linearization using a pharmacokinetic/pharmacodynamic model

We focus on the Fisher information matrix used for design evaluation and optimization in nonlinear mixed effects multiple response models. We evaluate the appropriateness of its expression computed by linearization as proposed for a single response model. Using a pharmacokinetic–pharmacodynamic (PKPD) example, we first compare the computation of the Fisher information matrix with approximation to one derived from the observed matrix on a large simulation using the stochastic approximation expectation–maximization algorithm (SAEM). The expression of the Fisher information matrix for multiple responses is also evaluated by comparison with the empirical information obtained through a replicated simulation study using the first‐order linearization estimation methods implemented in the NONMEM software (first‐order (FO), first‐order conditional estimate (FOCE)) and the SAEM algorithm in the MONOLIX software. The predicted errors given by the approximated information matrix are close to those given by the information matrix obtained without linearization using SAEM and to the empirical ones obtained with FOCE and SAEM. The simulation study also illustrates the accuracy of both FOCE and SAEM estimation algorithms when jointly modelling multiple responses and the major limitations of the FO method. This study highlights the appropriateness of the approximated Fisher information matrix for multiple responses, which is implemented in PFIM 3.0, an extension of the R function PFIM dedicated to design evaluation and optimization. It also emphasizes the use of this computing tool for designing population multiple response studies, as for instance in PKPD studies or in PK studies including the modelling of the PK of a drug and its active metabolite. Copyright © 2009 John Wiley & Sons, Ltd.     

One‐ and two‐stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint

Phase II clinical trials are performed to investigate whether a novel treatment shows sufficient promise of efficacy to justify its evaluation in a subsequent definitive phase III trial, and they are often also used to select the dose to take forward. In this paper we discuss different design proposals for a phase II trial in which three active treatment doses and a placebo control are to be compared in terms of a single‐ordered categorical endpoint. The sample size requirements for one‐stage and two‐stage designs are derived, based on an approach similar to that of Dunnett. Detailed computations are prepared for an illustrative example concerning a study in stroke. Allowance for early stopping for futility is made. Simulations are used to verify that the specified type I error and power requirements are valid, despite certain approximations used in the derivation of sample size. The advantages and disadvantages of the different designs are discussed, and the scope for extending the approach to different forms of endpoint is considered. Copyright © 2008 John Wiley & Sons, Ltd.     

胃癌大肠转移的X线钡灌肠表现

目的:分析胃癌大肠转移的X线钡灌肠表现。方法:104例胃癌入院术前检查发现结肠转移或胃癌术后转移入院治疗的病例。分析钡灌肠初次发现大肠转移征象的年龄、发现胃癌原发病变距初次发现大肠转移的间隔时间、转移病变的发生部位和病变造成的X线钡灌肠图像上的肠管变形和粘膜面的改变。结果:104例胃癌结肠转移,男67例,女37例。胃癌术前检查中发现结肠转移者32例,术后发现的大肠转移中,多数转移发生在手术后3年内(占91.3%)。胃癌原发灶的肉眼形态BorrmannⅢ型(28例)和BorrmannⅣ型(65例)者占89.4%,组织学中以低分化腺癌和印戒细胞癌为主要成分者占91.3%。X线钡灌肠检查显示大肠转移的好发部位为横结肠(80),其次为直肠(50)。转移灶可累及多节段肠管,其中横结肠中1/3段(47),横结肠左1/3(44),横结肠右1/3(39)和直肠腹膜返折之上(39)。X线显示肠管单侧变形者227处,双侧变形者96处。黏膜面表现为梳齿状黏膜纹聚集改变253处,颗粒结节状改变23处,外压性改变20处,弥漫性改变62处。结论:胃癌大肠转移的好发部位为横结肠和直肠,结肠黏膜面的梳齿状黏膜纹聚集为胃癌大肠转移的主要X线钡剂灌肠表现。     

Zolpidem induced nocturnal sleep‐related eating disorder (NSRED) in a male patient

Nocturnal Sleep‐Related Eating Disorder (NSRED) is a well‐documented sleeping disorder where the person is reported to experience bizarre eating behavior during sleep. Although various causes are implicated in this disorder, role of drugs cannot be ruled out. Here we narrate an interesting rare case report of a drug‐induced new onset NSRED, where a 45‐year‐old man on zolipdem performed an unexpected and bizarre eating behavior during somnambulistic state, type of which has not been reported earlier in the literature. The case falls under even rarer category as such behavior in sleep is reported mainly in woman. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2009     

Soul City: a sustainable edutainment vehicle facilitating social change

This paper outlines the programming model employed by the Soul City Institute for Health and Development Communication, a South African NGO, in using ‘edutainment’ to facilitate social change. The paper refers to the intersection of this model and current thought on health promotion and various social change theories. It also discusses key challenges and factors contributing to sustainability over 12 years.     

Pituitary adenomas: Trans‐sphenoidal experience of 300 cases

Objective: The main aim of the present study was to examine the effectiveness and complication rate of the 1 cm right‐sided unilateral sublabial trans‐sphenoidal surgery for patients with pituitary adenoma equal to or greater than 5 mm in diameter. Method: A total of 350 patients were surgically treated for pituitary adenomas between December 1999 and December 2003 in an academic neurosurgical unit in China. Three hundred patients (86%) were treated with the 1‐cm right‐sided unilateral sublabial trans‐sphenoidal approach. The mean age of patients was 43 years (range 10–78 years) and female patients accounted for 59% of the total. One hundred and ninety‐six (64%) patients had functioning endocrine tumours and 104 (36%) patients had non‐functioning tumours or macroadenomas. Tumours which were outside this simple and basic classification were excluded from the study. Results: There were no operative mortalities. One patient developed hypopituitarism and 16 (5%) developed transient diabetes insipidus that required pituitrin treatment. The remission rate for macroadenoma was 85% and that for microadenoma was 98.5% during a medium term follow‐up of 1–5 years. One hundred and fifteen patients had prolactin secreting tumours and 90.4% achieved endocrine remission. Fifty‐six patients had growth hormone secreting tumours and 75.4% achieved endocrine remission. Preoperatively, one hundred and fifty‐one patients presented with visual impairment and 148 (98%) achieved a documented improvement in visual acuity. The mean duration of hospital stay was 4 days (range 3–7 days). Conclusion: This minimally invasive trans‐sphenoidal surgery for pituitary adenomas could be used as the primary treatment for small pituitary tumours. The effectiveness of the tumour removal and low morbidity rate compare favourably with the conventional sublabial approach as well as the more recently developed endoscopic endonasal approaches.     

Alveolar hydatid disease of the liver: Brief review and spectrum of adjacent organ invasion

The purpose of this study is to show the spectrum of adjacent organ invasion and to make a brief review of hepatic alveolar hydatid disease (AHD), using CT and MR imaging. We retrospectively reviewed CT and MR images of three patients with various adjacent organ invasions surgically and histologically proven to be AHD. Local invasion to right kidney and adrenal, right hemidiaphragm and lung were detected in one patient, right adrenal in another patient and gall bladder, duodenum, gastric wall and pancreas invasion in the other. AHD may rarely extend to the gall bladder, stomach, duodenum, pancreas, right adrenal and kidney, diaphragm, pleura and lung. The extension of the disease outside the liver is usually encountered in patients with large, peripherally located masses in the advanced stage of the disease.