MSA-C is the predominant clinical phenotype of MSA in Japan: analysis of 142 patients with probable MSA

We investigated the clinical features and mode of disease progression in 142 patients with probable multiple system atrophy (MSA) according to the Consensus Criteria. The subjects included 84 men and 58 women with a mean age at onset of 58.2+/-7.1 years (range: 38-79 years). Cerebellar signs were detected in 87.3% of these patients at the time of initial examination, and were found in 95.1% of them at latest follow-up. MSA-C was diagnosed in 83.8% of the patients at their first examination. Parkinsonism was initially detected in 28.9% of the patients, increasing to 51.4% at the latest follow-up. Among all of the subjects, only 16.2% were classified as having MSA-P on initial examination. At the latest follow-up, parkinsonian features had become predominant over cerebellar features in 24.6% of the 65 patients with MSA-C who were followed for more than 3 years. Although parkinsonism usually masked the signs of cerebellar involvement in MSA-C patients, none of the patients with MSA-P at an early stage showed predominance of cerebellar features at the latest follow-up. Parkinsonism is the predominant feature of MSA among Western patients, even at an early stage, but this study showed that cerebellar deficits are the main feature in Japanese patients. This difference of disease manifestations between ethnic groups suggests that genetic factors may influence the clinical phenotype of MSA.     

Narrow band imaging and serology in the assessment of premalignant gastric pathology

Abstract

Background: Patient outcomes in gastric adenocarcinoma are poor due to late diagnosis. Detecting and treating at the premalignant stage has the potential to improve this. Helicobacter pylori is also a strong risk factor for this disease.

Aims: Primary aims were to assess the diagnostic accuracy of magnified narrow band imaging (NBI-Z) endoscopy and serology in detecting normal mucosa, H. pylori gastritis and gastric atrophy. Secondary aims were to compare the diagnostic accuracies of two classification systems using both NBI-Z and white light endoscopy with magnification (WLE-Z) and evaluate the inter-observer agreement.

Methods: Patients were prospectively recruited. Images of gastric mucosa were stored with histology and serum for IgG H. pylori and Pepsinogen (PG) I/II ELISAs. Blinded expert endoscopists agreed on mucosal pattern. Mucosal images and serological markers were compared with histology. Kappa statistics determined inter-observer variability for randomly allocated images among four experts and four non-experts.

Results: 116 patients were prospectively recruited. Diagnostic accuracy of NBI-Z for determining normal gastric mucosa was 0.87(95%CI 0.82–0.92), H. pylori gastritis 0.65(95%CI 0.55–0.75) and gastric atrophy 0.88(95%CI 0.81–0.94). NBI-Z was superior to serology at detecting gastric atrophy: NBI-Z gastric atrophy 0.88(95%CI 0.81-0.94) vs PGI/II ratio?p<.0001. Overall NBI-Z was superior to WLE-Z in detecting disease using two validated classifications. Inter-observer agreement was 0.63(95%CI 0.51–0.73).

Conclusions: NBI-Z accurately detects changes in the GI mucosa which currently depend on histology. NBI-Z is useful in the detection of precancerous conditions, potentially improving patient outcomes with early intervention to prevent gastric cancer.     

Prenatal diagnosis of ring chromosome 6 in a fetus with cerebellar hypoplasia and partial agenesis of corpus callosum: case report and review of the literature

Ring chromosome 6 (RC6) is a rare constitutional abnormality, with variable material loss, leading to a variable clinical phenotype: minimal physical anomalies and mild psychomotor retardation to severe physical and mental defects. Among the 22 published cases, only five have been prenatally detected. We describe here a RC6 prenatally diagnosed. Ultrasound follow-up showed growth retardation and cerebellar hypoplasia. Magnetic resonance imaging (MRI) confirmed this, but showed a partial corpus callosum agenesis, leading to amniocentesis and revealing the chromosomal abnormality. Imaging features were correlated with autopsy findings.     

黄芪与丹参联合对大鼠失神经骨骼肌萎缩的作用

目的探讨黄芪与丹参联合应用对失神经骨骼肌萎缩的作用。方法健康成年雄性SD大鼠72只,随机分为3组:阴性对照组(A组,n=24)、失神经对照组(B组,n=24)、黄芪丹参治疗组(C组,n=24)。A组仅暴露右侧坐骨神经,但不切断;B、C两组切断右侧坐骨神经1 cm,建立右下肢失神经腓肠肌萎缩模型;B组腹腔注射3 mL生理盐水;C组采用黄芪、丹参各1.5mL混合腹腔注射给药,分别于术后第2、3、4、6周每组各处死6只大鼠进行腓肠肌肌湿重比值和肌纤维横切面积检测。结果在第2、3、4周,治疗组的肌湿重比值、肌纤维横截面积均显著高于模型组(P<0.05);在第6周时,治疗组肌湿重比值、肌纤维横截面积与模型组相比无显著性差异(P>0.05)。结论在失神经早期,黄芪丹参联合应用能有效延缓大鼠因失神经所致的骨骼肌萎缩,其发生的机制有待进一步研究。     

Perfluoroalkylated compounds induce cell death and formation of reactive oxygen species in cultured cerebellar granule cells

The present communication investigates the effects of different perfluoroalkylated compounds (PFCs) on formation of reactive oxygen species (ROS) and cell death in cultured cerebellar granule cells. This allows direct comparison with similar effects found for other environmental contaminants like polychlorinated biphenyls and brominated flame-retardants. The increase in ROS formation and cell death was assayed using the fluorescent probe 2,7-dichlorofluorescin diacetate (DCFH-DA) and the trypan blue exclusion assay. The effects of the PFCs were structure dependent. Cell death was induced at relatively low concentrations by perfluorooctyl sulfonate (PFOS), perfluorooctane sulfonylamide (PFOSA) and the fluorotelomer alcohol 1H, 1H, 2H, 2H-perfluorodecanol (FTOH 8:2) with EC₅₀-values of 62 ± 7.6, 13 ± 1.8 and 15 ± 4.2 μM (mean ± SD) respectively. PFOS, perfluorooctanoic acid (PFOA) and PFOSA induced a concentration dependent increase in ROS formation with EC₅₀-values of 27 ± 9.0, 25 ± 11 and 57 ± 19 μM respectively. Reduced cell viability and ROS formation were observed at concentration level close to what is found in serum of occupationally exposed workers. The effect of PFCs on ROS formation and cell viability was compared with other halogenated compounds and future investigations should emphasize effects of mixtures and how physical chemical properties of the compounds influence their toxicity.     

Novel therapies for muscular dystrophy and other muscle wasting conditions

The muscular dystrophies are generally characterised by progressive skeletal muscle wasting and weakness. Duchenne muscular dystrophy (DMD), an X-linked disorder, is the most severe of all the dystrophies and is caused by a variety of mutations and deletions in the dystrophin gene. In the absence of dystrophin expression, the skeletal muscles of boys with DMD undergo continuous cycles of degeneration and regeneration of muscle fibres that lead to a progressive wasting of the skeletal muscles. At age 10 years, DMD patients have only 25% of the muscle mass of healthy children and the functional burden on their weakened muscles is too great for normal ambulation well before this time. They become dependent on a wheelchair before their early teens and die of respiratory or heart failure by their early 20’s. There is a profound need for therapeutic intervention strategies that aim to cure or ameliorate the dystrophic condition and improve the quality of life for these patients. Therapeutic approaches for muscular dystrophy fall into two classes: those that attempt to ameliorate the dystrophic condition through pharmacological interventions, or those that attempt to overcome the gene defect. The greatest likelihood of a cure for DMD and other muscular dystrophies will eventually be derived from gene therapy. However, problems continue to plague this research, including: the limitation of the spread of expression from injection sites in the muscle, the longevity of expression, the need for systemic delivery, vector design and carrying capacity, and difficulties with immunosuppression. Sadly, until these techniques are perfected, boys with DMD will die and patients with other less severe neuromuscular conditions will continue to lose muscle mass and function. This review examines recent (1997 - 2000) patents on novel therapies for muscular dystrophy and evaluates their potential for ameliorating muscle wasting and/or improving muscle function.     

Pharmacotherapy of age-related macular degeneration

Background: Age-related macular degeneration is the leading cause of blindness in the developed world. The number of persons with vision loss from age-related macular degeneration is projected to increase dramatically over the next few decades. Therefore, effective therapeutic and prophylactic agents are greatly needed. Objective: This article will discuss some of the newer treatment strategies that may help to reduce the incidence of visual loss from age-related macular degeneration. Some of these therapies and strategies can be implemented today, while many are hypothetical based on current laboratory data and ongoing clinical trials. Methods: A review of the literature and ongoing clinical trials was undertaken. Conclusion: Current therapies using antioxidants for prevention of the progression of age-related macular degeneration and anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration have given us tools for tackling this disease better and reducing the number of patients with vision loss. Combinations of some of the existing treatments and new forms of therapy may yet further decrease the treatment burden in the future.     

Treatment of menopausal symptoms post-Women’s Health Initiative: refinement of existing treatments and development of new therapies

Menopause is a normal life transition for women. More than 80% of women experience some symptoms at menopause and > 25% of women in western countries seek treatment for a variety of symptoms that accompany this transition. In addition, there are certain chronic disease processes that accelerate after the menopausal transition. Hormone replacement therapy (HRT) with various combinations of oestrogen and progesterone compounds has been the mainstay of treatment for menopausal symptoms, as well as theoretical reduction in acceleration of certain chronic diseases after menopause. After the publication of the results of the Women’s Health Initiative study in June 2002, the safety of HRT, as well as its effectiveness in decreasing various chronic diseases, was challenged. New formulations of hormone therapy, as well as new treatments, are evolving to aid the reduction of menopausal symptoms and long-term risks of common chronic disease processes that accelerate after the menopause.     

四物汤配方颗粒联合复方樟柳碱治疗外伤性视神经萎缩的临床研究

目的探讨四物汤配方颗粒联合复方樟柳碱治疗外伤性视神经萎缩的效果。方法选择2009年1月～2011年12月于本院接受治疗的外伤性视神经萎缩患者64例。其中32例采用常规治疗作为对照组,另外32例患者在对照组治疗基础上加用四物汤配方颗粒治疗为研究组。1个月为1个疗程,观察两组患者治疗前后视力、视野的变化。结果对照组有效率为78．13％,研究组有效率为90．63％,两组比较差异有统计学意义（P〈0．05）。与治疗前视野比较,两组治疗后视野改善明显,差异有统计学意义（P〈0．05）;治疗后,与对照组视野比较,研究组视野改善明显。差异有统计学意义（P〈0．05）。结论四物汤配方颗粒联合复方樟柳碱治疗视神经萎缩效果显著,值得临床推广。