分子バイオマーカーと診断のジャーナル

Tremor is the most common movement disorder. The objective of the current study was to find correlation between disability due to tremor (daily living score) with the functional performance tests like nine-hole peg and box and block. A total of 100 subjects with tremor, categorized in seven diagnostic groups fulfilling the respective diagnostic criteria studied. Clinical assessment using activities of daily living scales (ADL-T24) and tremor severity score done on each patient. The nine-hole peg score (in seconds) and box and block score (number of blocks in 60 seconds) calculated in each. We found that tremor severity was proportionate to ADL-T24 score and had a positive correlation with the disease duration. Overall, there was a moderate positive correlation between ADL-T24 score and 9-HPT score (R2=0.52) whereas a strong negative correlation between ADL-T24 and BBT score (R2=-0.66). An inverse pattern was observed between 9-HPT score and BBT score with a moderate negative correlation (R2=-0.58). It was concluded that the functional performance tests correlate well with the daily living scores. Thus the tremor severity can be quantified on time based measures and are useful for tremor assessment.

Background: Long term administration of antiepileptic drug phenytoin is reported to cause behavioral abnormalities mediated via oxidative stress. The effect of an antioxidant alpha lipoic acid (ALA) against phenytoin induced behavioral abnormalities was investigated.

Methods: The study was carried out in albino wistar rats. The rats were divided into five groups of six animals each. Group 1 received 0.2% carboxy methyl cellulose (CMC, p.o), group 2 received 20 mg/kg phenytoin (p.o), groups 3,4 and 5 received 50, 100 and 200 mg/kg (p.o) of ALA in 0.2% CMC, respectively 1 h prior to phenytoin for 45 days. Motor coordination, exploratory behavior, memory and spontaneous motor activity were evaluated by Rota rod, Hole board, Elevated plus maze and Actophotometer respectively. On day 45, regional brain lipid peroxidation and acetylcholinesterase (ACh E) activity along with brain histopathological investigation were performed after euthanasia. In addition, pharmacokinetic and pharmacodynamic drug interactions between phenytoin and ALA were also studied.

Results: Long term administration of phenytoin showed behavioral abnormalities, increased regional brain malondialdehyde (MDA) and ACh E activity. The histopathological investigation showed congested and damaged cells in brain regions. ALA substantially reversed phenytoin induced behavioral abnormalities, oxidative stress and alleviated the histopathological abnormalities. There were no significant differences in the serum levels of phenytoin and the degree of protection offered by phenytoin in ALA supplemented groups revealing that there were no pharmacokinetic and pharmacodynamic interactions between phenytoin and ALA.

Conclusion: This study reports the effectiveness of ALA against phenytoin induced behavioral abnormalities and oxidative stress in rats without altering the bioavailability of phenytoin and its therapeutic effect.

Histone acetylases [HAT] and histone deacetylases [HDACs] are responsible for the addition and removal of acetyl-groups to or from specific lysine residues located within histone tails and a number of non-histone proteins. HDACs, as one of the epigenetic mechanisms, play a central role in the regulation of cellular properties that related to development and progression of cancer. Recently, researches began to focus on the expression patterns of HDAC isoforms as a biomarker in cancer. It could be used to find new agents that are very effective in inducing apoptosis, differentiation, and/or cell growth arrest in neoplasia. Approximately, all of studies showed HDAC expression level differ in human tumors. For example, in most tumor entities class I HDAC expression was higher in late stage, high-grade tumors with strong proliferative activity and Class II HDACs down regulated in human tumors and high expression in some tumors was linked to a better prognosis. Thus, this factor allowed to opens new possibilities for a molecularly targeted approach to treatment.

Background: Prostate cancer is the most common cancer in men in the developed world. Appropriate clinical care requires accurate prognostic information to determine whether definitive treatment or conservative management is most appropriate for a given patient. We previously demonstrated that a gene expression signature, which measures the RNA expression of 31 cell cycle progression (CCP) genes and generates a CCP score, is a robust predictor of patient outcome in cohorts of conservatively managed patients diagnosed by needle biopsy or transurethral resection of the prostate.

Methods: These current studies represent the analytical validation of this gene signature, for the testing of either formalin-fixed paraffin-embedded (FFPE) prostate resection tissue (radical prostatectomy, RP) or FFPE prostate needle biopsy samples.

Results: The measured standard deviation (SD) of the signature was determined to be 0.1 score units, representing 1.6% of the range of scores observed within previous clinical validation studies. Individual amplicons for all genes within the signature had a SD <1 CT, with a median SD of 0.52 CT’s. We observed the median amplification efficiency for all genes was 92.6%. The linear range of the signature was over a ~260-fold range of RNA concentrations. We observed that 100% of RP samples and 99.8% of needle biopsy samples produced sufficient RNA for testing, when RNA was extracted from 7,525 recent prostate samples. Finally, RNA samples were able to reproduce similar CCP scores when stored for up to 8 weeks.

Conclusion: These studies indicate that this prognostic gene signature is robust and reproducible, and is analytically validated for use on FFPE prostate biopsy radical prostatectomy samples.

Background: The pattern of stroke displays ethnic and geographical variations. In Sub-Saharan Africa there is scarcity of data from Eastern and Central Africa.

Objective: To describe the characteristics of patients with ischemic cortical stroke in a Kenyan referral hospital.

Study design and set up: Retrospective study at Kenyatta National Hospital, Nairobi Kenya.

Patients and methods: Records of adult black Kenyan patients seen with ischemic cortical stroke at Kenyatta National Hospital, Nairobi, Kenya between January 2007 and December 2011 were examined for age, sex, site, comorbidities and outcome. Only files with complete data were included. Data were analyzed by SPSS version 17.0 for Windows and presented in tables and bar charts.

Results: Three hundred and seven cases of ischemic cortical stroke were analyzed. Mean age was 54.7 years, with 20.6% of cases occurring below 40 years. The male: female ratio was 1:1.2 with female predominance in all age groups. Brain regions most commonly affected were fronto-parietal (32.8%) and parietal (31.6%), while 11.6% involved extensive regions of the cerebral cortex. Predominant single comorbidities were hypertension (64.1%), smoking (19.2%), alcohol (13.4%), HIV infection (6.8%) and bacterial infections (6.8%). Multiple risk factors were implicated in 42.4% cases. Two hundred (65.1%) suffered paralysis; 70 (22.8%) clinically recovered and 37 (12.1%) died within 90 days.

Conclusion: Ischemic cortical stroke occurs in young individuals in over 20% of the study population and is female predominant. Hypertension, cigarette smoking and infections including HIV are the leading comorbidities, and it causes high morbidity. Control measures comprising regulation of blood pressure, reduction of smoking and prudent management of infections should be instituted from early in life.

Introduction:Psychiatric disorders may be encountered in certain central nervous system diseases. In multiple sclerosis (MS) some of these manifestations have been described and are not necessarily related to the psychological impact of such disabling disease. The link between these disorders and MS remains incompletely determinated.

Case report: We report a case of a 31 years old women, diagnosed since March 2010 for MS. She developed two neurological episodes: retrobulbar optic neuritis and lower limb paresthesia. She fulfilled Barkhof's MRI criteria. The new episode was associated with concomitant melancholia and psychiatric symptoms. Brain magnetic resonance imaging revealed a new frontal lesion. Biological balance was normal. The diagnosis of MS attack was established. Given to treat acute episodes, high-dose corticosteroids enabled regression of the psychological fits.

Discussion: Psychiatric disorders in MS have been described since 1926. Patients may have mood disorders, personality disorders or psychosis. Thus, the occurrence of psychiatric disorder during the MS is no longer regarded as an atypical subject. They seem to occur on average one year after diagnosis of MS. More rarely, they can usher the clinical picture. The possibility of isolated "psychiatric attack" in MS cannot be excluded. Hypothesis reinforced by the good response of psychiatric symptoms to steroids and the presence of a concomitant gadolinium enhancing lesion.

Conclusion: This case report adds to those in the literature, making psychiatric disorder a possible manifestation of MS. The psychiatric symptoms-MS association may be due to local MS-related brain damage or a common genetic susceptibility.