Does lowering the screening age for cervical cancer in The Netherlands make sense?

Recommendations for the age to initiate cervical cancer screening should be directed towards maximum detection of early cervical cancer. However, the screening programme should do more good than harm. The aim of this analysis was to determine whether the target age for cervical cancer screening should be lowered in view of apparent increases in new cases of invasive cancer below age 30 and in age group 30-44 years in The Netherlands. Therefore, all cervical cancer cases diagnosed between January 1, 1989 and December 31, 2003 were selected from the nationwide population-based Netherlands Cancer Registry. For age group 25-39 years, incidence data were also available for 2004 and 2005. To describe trends, the estimated annual percentage of change and joinpoint analysis were used. Between ages 25 and 28 years, the absolute number of new cases of cervical cancer annually has varied between 0 and 9 per age. Significantly decreasing trends in incidence were observed for age groups 35-39 and 45-49 (p < 0.0001 and p = 0.01, respectively). The annual number of deaths fluctuated with a decreasing trend for age groups 30-34 and 35-39 years (p = 0.01 and p = 0.03, respectively). Because the incidence and mortality rates for cervical cancer among women younger than 30 are low and not increasing, lowering the age for cervical cancer screening is not useful at this time. Although the number of years of life gained is high for every case of cervical cancer prevented, the disadvantages of lowering the screening age would be very large and even become disproportionate compared to the potential advantages.     

Electroconvulsive therapy and/or plasmapheresis in autoimmune encephalitis?

Autoimmune encephalitis is a poorly understood condition that can present with a combination of neurological and psychiatric symptoms, either of which may predominate. There are many autoantibodies associated with a variety of clinical syndromes - anti-N-Methyl-D-Aspartate receptor (NMDAR) is the commonest. Currently, the most widely used therapy is prompt plasmapheresis and steroid treatment (and tumour resection if indicated), followed by second line immunosuppression if this fails. Given the growing awareness of autoimmune encephalitis as an entity, it is increasingly important that we consider it as a potential diagnosis in order to provide timely, effective treatment. We discuss several previously published case reports and one new case. These reports examined the effects of electroconvulsive therapy (ECT) on patients with autoimmune encephalitis, particularly those in whom psychiatric symptoms are especially debilitating and refractory to standard treatment. We also discuss factors predicting good outcome and possible mechanisms by which ECT may be effective. Numerous cases, such as those presented by Wingfield, Tsutsui, Florance, Sansing, Braakman and Matsumoto, demonstrate effective use of ECT in anti-NMDAR encephalitis patients with severe psychiatric symptoms such as catatonia, psychosis, narcolepsy and stupor who had failed to respond to standard treatments alone. We also present a new case of a 71-year-old female who presented to a psychiatric unit initially with depression, which escalated to catatonia, delusions, nihilism and auditory hallucinations. After anti-NMDAR antibodies were isolated, she was treated by the neurology team with plasmapheresis and steroids, with a partial response. She received multiple sessions of ECT and her psychiatric symptoms completely resolved and she returned to her premorbid state. For this reason, we suggest that ECT should be considered, particularly in those patients who are non-responders to standard therapies.     

Tumour suppressor HLJ1: A potential diagnostic,preventive and therapeutic target in non-small cell lung cancer

Lung cancer is the leading cause of cancer-related mortality throughout the world. Non-small cell lung cancer (NSCLC) accounts for 85% of all diagnosed lung cancers. Despite considerable progress in the diagnosis and treatment of the disease, the overall 5-year survival rate of NSCLC patients remains lower than 15%. The most common causes of death in lung cancer patients are treatment failure and metastasis. Therefore, developing novel strategies that target both tumour growth and metastasis is an important and urgent mission for the next generation of anticancer therapy research. Heat shock proteins (HSPs), which are involved in the fundamental defence mechanism for maintaining cellular viability, are markedly activated during environmental or pathogenic stress. HSPs facilitate rapid cell division, metastasis, and the evasion of apoptosis in cancer development. These proteins are essential players in the development of cancer and are prime therapeutic targets. In this review, we focus on the current understanding of the molecular mechanisms responsible for HLJ1’s role in lung cancer carcinogenesis and progression. HLJ1, a member of the human HSP 40 family, has been characterised as a tumour suppressor. Research studies have also reported that HLJ1 shows promising dual anticancer effects, inhibiting both tumour growth and metastasis in NSCLC. The accumulated evidence suggests that HLJ1 is a potential biomarker and treatment target for NSCLC.     

Development and Implementation of National Practice Guidelines: A Prospect for Continuous Quality Improvement in Physiotherapy: Introduction to the method of guideline development

The development of national practice guidelines (NPGs) is an issue of much concern in healthcare policies world-wide to guarantee and to improve the quality and efficiency of care. The development and implementation of NPGs constitutes an important part of the quality of care policy of the Royal Dutch Physiotherapy Association (KNGF). This interest is due to pressure from society (policy-makers, healthcare managers, financiers and patients) on physiotherapists to ensure quality of care and to justify our position in the healthcare system. The development of NPGs can also be seen as a logical step in the process of professionalisation and quality assurance by physiotherapists.An NPG is described as a systematically developed statement, drafted by experts and directed at one aspect of the treatment of a health problem belonging to the domain of the profession. NPGs are based on the different stages of the physiotherapy care process, the available clinical evidence and expert consensus. Priority is given to a cost-effective approach and multidisciplinary consensus on diagnosis, treatment and primary or secondary prevention. Recommendations are based on the results of new or recorded systematic reviews or meta-analysis.NPGs are important state-of-the-art documents, which can guide professionals in their daily practice and make explicit to other relevant people what professionals can do in a certain situation or with a specific condition, and why they do it. NPGs have important functions, including supporting physiotherapists in their decision-making process; they are a frame of reference for orientation and educational purposes, they provide criteria for self-evaluation and peer review, and can initiate changes in established practice patterns.This paper describes the process and development of NPGs for physiotherapists in the Netherlands. In a companion paper the method and strategies for the implementation of NPGs and the need for evaluation of their outcome will be discussed.     

Ghrelin function in human obesity and type 2 diabetes: a concise review

The 28 amino acid hormone, ghrelin, has been found to have various effects on metabolism. This review will focus on the pathways integrated into ghrelin's effect within the hypothalamus, pancreas and adipocytes. The identification of molecules and pathways that regulate ghrelin‐mediated lipid retention could establish new mechanisms underlying cellular energy homeostasis. The impact of acyl‐ghrelin on glucose metabolism and lipid homeostasis may allow for novel preventative or early intervention therapeutic strategies to treat obesity related type 2 diabetes and associated metabolic dysfunction.     

组织浓度的意义

过去几十年至今,人们普遍以组织药物浓度来推测抗生素的活性和MIC,将组织匀浆液中测得的药物浓度与相应血浆中的药物浓度的比值来指导药物的临床应用。然而从药动学和药效学角度看这种方法并不合理,并最终可能对病人产生潜在危害。全组织药物浓度通常是通过测定碾碎或溶解后的匀浆组织的药物浓度而得到,这种测定方法忽略了组织的内部结构(如间质液、细胞及亚细胞结构等),药物不一定是均匀分布于组织中,并且,组织匀浆的药物浓度不能完全反映药物的有效活性。所以全组织药物浓度不能真实反应抗生素在感染部位的浓度。比如:多数细菌的感染部位在细胞外,故细胞外药物浓度才是关注的焦点。对于主要分布于胞外的药物,组织碾碎后使细胞内外液混合,则测得的药物浓度会低于实际感染部位的浓度;相反,对于主要分布于胞内的药物,测得的全组织浓度会大大高于细胞外浓度。对于胞内菌感染也可得相应结论。给药后抗生素会分布到全身不同部位,大多数药动学可以用二室或三室模型模拟。由于室间不能瞬间达到平衡,所以各室的药-时曲线也可能出现很大差异。在某时刻采集全组织样本就可获得该时间点组织浓度与血药浓度的比值。为了减少干扰,应在同一病人上采集达稳态的样品,但这并不可行且存在伦理学问...     

建立胫骨癌痛模型的理论与实践

目的:骨癌痛动物模型已有报道,但还没有可接受的与人类骨癌痛相一致的模型。综述胫骨癌痛模型的研究进展及相关治疗前景。资料来源:应用计算机检索Medline1996-01/2006-03相关胫骨、癌痛和治疗的文献,检索词“tibial,cancerpain,therapy”,并限定文献语言种类为English。同时检索万方数据库1996-01/2006-05文献,检索词为“胫骨癌痛”,并限定语言种类为中文。资料选择:对资料进行初审,选取包括胫骨、癌痛和治疗的文献,开始查找全文。纳入标准:①胫骨和癌痛。②癌痛和治疗。排除标准:综述文献、重复研究、Meta分析类文章。资料提炼:共收集到51篇关于胫骨、癌痛和治疗的文献,纳入30篇关于胫骨和癌痛,癌痛和治疗的文献。资料综合:①目前认为,胫骨癌痛动物模型的疼痛表现与临床上所见的骨转移症状相似,可视为转移性骨癌痛模型。②恶性肿瘤骨损害的特征性变化是溶骨性骨吸收和恶性肿瘤疼痛本身,随骨质破坏的加剧,疼痛逐渐增强,移动或轻触可以引发急性痛,在到达极度痛之前,常因运动、负重或自发地间断发生突破痛,其发生的程度和频率与骨质破坏和溶骨活性成正相关。③目前从胫骨癌痛的实验研究中发现可供选择的药物主要有阿片类药、5-羟色胺受体阻断剂、抗惊厥药物加巴喷丁、环氧化酶2抑制剂表皮生长因子阻断剂。结论:利用动物胫骨癌痛模型来研究人类骨癌痛是可行的,但其研究有待进一步深入。从胫骨癌痛的实验研究中发现有许多药物可供选择,这展示了药物治疗骨癌痛的应用前景。     

Was There Shortening of the Interval Between Diagnosis and Treatment of Colorectal Cancer in Southern Netherlands Between 2005 and 2008?

Background  

The Dutch Cancer Society proposed that the interval between diagnosis and start of treatment should be less than 15 working days. The purpose of this study was to determine whether the interval from diagnosis to treatment for patients with colorectal cancer (CRC) shortened between 2005 and 2008 in hospitals in southern Netherlands.     

Simian virus 40 large tumor antigen forms specific complexes with p53 and pRb in human brain tumors

Objective　To study the role of simian virus 40 (SV40) early region gene coding product large tumor antigen (Tag) expression and the interaction between Tag and tumor suppressors p53 and pRb in human brain tumorigenesis. Methods　Tag was investigated by immunoprecipitation followed by silver staining and Western blot in 65 cases of human brain tumors and 8 cases of normal brain tissues. Tag-p53 and Tag-pRb complexes were screened in 18 and 15 Tag positive tumor tissues, respectively. Results　Tag was found in all 8 ependymomas and 2 choroid plexus papillomas, 90% of pituitary adenomas (9/10), 73% of astrocytomas (11/15), 70% of meningiomas (7/10), 50% of glioblastomas multiforme (4/8), 33% of medulloblastomas (2/6). 5 oligodendrogliomas, 1 pineocytoma, and 8 normal brain tissues were negative for Tag. Tag-p53 complex was detected in all 18 Tag positive tumors. Tag-pRb complex was found in all 15 Tag positive tumors. Conclusion　SV40 Tag is expressed in human brain tumors and can form specific complexes with tumor suppressors p53 and pRb. The inactivation of p53 and pRb due to the formation of Tag-p53 and Tag-pRb complexes may be an important mechanism in the etiopathogenesis of human brain tumors.