Decreased bone density and treatment in patients with autosomal recessive cutis laxa

Aim: Due to the occasional association pathological fractures and osteoporosis we evaluated four patients with cutis laxa syndrome for skeletal anomalies.
Patient/Methods: We prospectively evaluated four patients, a male and a female child and a brother-sister sib pair, with dysmorphic features, growth delay, joint anomalies, psychomotor retardation and congenital cutis laxa. The clinical features and the family history were suggestive for autosomal recessive cutis laxa syndrome type II, partially overlapping with geroderma ostedysplastica. Skeletal survey, sequential bone density measurements, endocrine and metabolic investigations were performed including N- and O-linked glycosylation analysis. ATP6V0A2 and FBLN5 mutations were ruled out in all patients.
Results: All children were diagnosed with significantly decreased bone density, especially in the lumbar spine, including spontaneous vertebral and rib fractures in three children. Following 24 months of bisphosphonate treatment a total restitution of bone density was observed in three cases and no relapse was detected in the 2-year follow-up period. A spontaneous improvement was found in one female during puberty.
Conclusion: Bone disease might occur early in the course in autosomal recessive cutis laxa syndrome. We report on a significant clinical improvement and stabilization in our patients following bisphosphonate therapy. We suggest early, systemic evaluation and follow up of bone density in all children presenting with inherited cutis laxa.     

Analysis of N-ras gene mutation and p53 gene expression in human hepatocellular carcinomas

ＡｎａｌｙｓｉｓｏｆＮｒａｓｇｅｎｅｍｕｔａｔｉｏｎａｎｄｐ５３ｇｅｎｅｅｘｐｒｅｓｓｉｏｎｉｎｈｕｍａｎｈｅｐａｔｏｃｅｌｕｌａｒｃａｒｃｉｎｏｍａｓＬＵＯＤａｎ１，ＬＩＵＱｉＦｕ１，ＣＧｏｖｅ２，ＮＶＮａｏｍｏｖ２，ＳＵＪｉａｎＪｉａ１ａ...     

治疗膝骨关节炎近十年文献中特殊内服中药分析

目的:总结和分析近10年国内医学期刊公开发表的中药内服治疗膝骨关节炎的文献中特殊中药应用现状。方法:通过统一检索式,委托专业文献查新人员检索万方、维普、CNKI三大数据库,再通过纳入标准、排除标准、资料提取与文献质量评价3个环节对检索结果进行分析。并对药物分类、特殊用药前20位药物出现频次及出现百分率进行排序。结果:最终有效文献为491篇,其中出现特殊用药的文献有209篇。中药内服治疗膝骨关节炎特殊用药前20位的药物排序依次为川乌、细辛、蜈蚣、附子、土鳖虫、草乌、全蝎、半夏、胆南星、马钱子、桃仁、红花、乌梢蛇、水蛭、血竭、三七、延胡索、路路通、穿山甲、白花蛇;药物功效分类依次为祛风寒湿药、活血止痛药、活血调经药、活血疗伤药、破血消癥药、息风止痉药、发散风寒药、温里药、温化寒痰药、化瘀止血药。结论:风、寒、湿三邪可能为膝骨关节炎的主要致病外因;膝骨关节炎风寒湿痹证出现的频率可能要比热痹证出现的频率高。     

Preclinical safety and biodistribution assessment of Ad-KCNH2-G628S administered via atrial painting in New Zealand white rabbits

Post-operative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Despite implementation of several pharmacological strategies, incidence of POAF remains at approximately 30%. An adenovirus vector encoding KCNH2-G628S has proven efficacious in a porcine model of AF. In this preclinical study, 1.5 × 10¹⁰ or 1.5 × 10¹² Ad-KCNH2-G628S vector particles (vp) were applied to the atrial epicardium or 1.5 × 10¹² vp were applied to the whole epicardial surface of New Zealand White rabbits. Saline and vector vehicle served as procedure controls. Animals were followed for up to 42 days. Vector genomes persisted in the atria up to 42 days, with no distribution to extra-thoracic organs. There were no adverse effects attributable to test article on standard toxicological endpoints or on blood pressure, left atrial or ventricular ejection fractions, electrocardiographic parameters, or serum IL-6 or troponin concentrations. Mononuclear infiltration of the myocardium of the atrial free walls of low-dose, but not high-dose animals was observed at 7 and 21 days, but these changes did not persist or affect cardiac function. After scaling for heart size, results indicate the test article is safe at doses up to 25 times the maximum proposed for the human clinical trial.     

Treatment of children with neurogenic bladder dysfunctions using dynamic nero-electrostimulation(DENS) and M-Cholinolytic therapy

【Objective】 To investigate effects of combined usage of dynamic neuro-electric stimulation(DNES) and M-cholynolytic therapy(oxybutynin) upon manifestations of neurogenic bladder dysfunctions(NBD) in children.【Method】 Urodynamics examination included registration of extemporaneous urinary excretion,urofluometry,and retrograde cytometry in horizontal and vertical position by example of urodynamic system(UDS) ACS 180 Plus(MENFIS BioMed.,USA).In accordance to severity of clinician manifestations,three groups of patients have been defined(27-highest one,49-middle and 51 low levels).Dynamic neuro-electrostimulation(DNES) procedures were conducted using the"DiaDNES-PKM"device(Russian Federation).The children were exposed to juxtaspinal stimulation on S1-S3 level-altogether 10 sessions have been performed.Oxybutynin(driptan) was used in dosage of 2.5 mg per diem.【Result】It was established that combined usage of DNES and oxybutynin in the group with highest severity caused the reduction of manifestations by 3.1 times while separately given DNES and basic therapy were followed by 34.1% and 28.0% reduction correspondently.Meanwhile,DNES and oxybutynin reduced severity in patients with pronounced disturbances by 7.5 times.Combined usage of oxybutynin and DNES in severely manifested NBD increased the effective volume of bladder by 2.3 times.Also significant reduction of both intrabladder pressure(by 48.0%) and compliance of the bladder(by 4.8 times) were detected under condition of combined usage of DNES and oxybutynin.All mentioned indices were modified to less extent in case of separate usage of DNES or oxybutynin when compared with the one registered after the combined their usage(P <0.05).【Conclusion】Combined usage of DENS and oxybutinin(driptan) is effective in most severe cases in children suffered from neurogenic overactive bladder.