A new direction for Alzheimer's research

Despite decades of research, at present there is no curative therapy for Alzheimer＇s disease. Changes in the way new drugs are tested appear to be necessary. Three changes are presented here and will be discussed. The first change is that Alzheimer＇s disease must be considered a disease of four major pathological processes, not one. The four processes are： 1） vascular hy- poperfusion of the brain with associated mitochondrial dysfunction, 2） destructive protein inclusions, 3） uncontrolled oxidative stress, and 4） proinflammatory immune processes second- ary to microglial and astrocytic dysfunction in the brain. The second change recommended is to alter the standard cognitive measurement tools used to quantify mental decline in test patients. Specifically the Dementia Severity Rating Scale （DSRS） should supersede Mini-Mental State Examination （MMSE） and other popular tests, and a measurement scale developed in research should be used to produce a linear and non-irregular baseline. Finally, accepting the concept that four etiologies cause Alzheimer＇s disease leads to the last necessary change, that new thera- pies must be employed directed against all four causes, likely as a combination. There are drugs ready to be employed in such a combinations which are available and used clinically for other purposes so can be used ＂offlabel＂ and one such combination is suggested.

Clinical characteristics of pediatric patients with treatment-refractory Tourette syndrome:An evidence-based survey in a Chinese population

BACKGROUND Tourette syndrome(TS)is a complex neurodevelopmental condition marked by tics,as well as a variety of psychiatric comorbidities,such as obsessivecompulsive disorders(OCDs),attention deficit hyperactivity disorder(ADHD),anxiety,and self-injurious behavior.TS might progress to treatment-refractory Tourette syndrome(TRTS)in some patients.However,there is no confirmed evidence in pediatric patients with TRTS.AIM To investigate the clinical characteristics of TRTS in a Chinese pediatric sample.METHODS A total of 126 pediatric patients aged 6-12 years with TS were identified,including 64 TRTS and 62 non-TRTS patients.The Yale Global Tic Severity Scale(YGTSS),Premonitory Urge for Tics Scale(PUTS),and Child Behavior Checklist(CBCL)were used to assess these two groups and compared the difference between the TRTS and non-TRTS patients.RESULTS When compared with the non-TRTS group,we found that the age of onset for TRTS was younger(P<0.001),and the duration of illness was longer(P<0.001).TRTS was more often caused by psychosocial(P<0.001)than physiological factors,and coprolalia and inappropriate parenting style were more often present in the TRTS group(P<0.001).The TRTS group showed a higher level of premonitory urge(P<0.001),a lower intelligence quotient(IQ)(P<0.001),and a higher percentage of family history of TS.The TRTS patients demonstrated more problems(P<0.01)in the“Uncommunicative”,“Obsessive-Compulsive”,“Social-Withdrawal”,“Hyperactive”,“Aggressive”,and“Delinquent”subscales in the boys group,and“Social-Withdrawal”(P=0.02)subscale in the girls group.CONCLUSION Pediatric TRTS might show an earlier age of onset age,longer duration of illness,lower IQ,higher premonitory urge,and higher comorbidities with ADHD-related symptoms and OCD-related symptoms.We need to pay more attention to the social communication deficits of TRTS.

Evaluating therapeutic outcome in epileptic patients using the changes of interval and duration

BACKGROUND： Seizure frequency is in abnormal distribution, and it is not enough to express the trend of concentration using means, and its median loses a lot of information, thus it lacks of a standard for evaluating the therapeutic effects based on seizure frequency. OBJECTIVE： To establish a method for evaluating the therapeutic effects on anti-epileptic drugs using changes of interval and duration of seizure. DESIGN： A prospective cohort study. SETTING： Zhumadian Psychiatric Hospital. PARTICIPANTS： Outpatients and inpatients suffering from epilepsy attending firstly visited Zhumadian Psychiatric Hospital from June 2001 to June 2002 were enrolled. They were diagnosed as epileptic according to the International Classification of Epileptic Seizure by International League Against Epilepsy （1981） based on the clinical history, physical examination, and investigations. The interval time was no more than 6 months. Informed consent was obtained from all the subjects, and the study was approved by the hospital ethical committee. METHODS： ① For the first visit and each follow-up, the following data were recorded, including general demographic information, seizure type, the date and time of ictus, the duration of ictus, and inducement or situation related, according to which the following indexes could be calculated, including seizure styles, interval, duration, cluster frequency and cluster duration. The information from the first review was noted as annals A. The second interview was taken at the end of the evaluating period; the information from the second review was noted as annals B. The third interview was taken within two weeks after the second one; the information from the third review was noted as annals C. The annals B or the annals C were respectively compared with the annals A in the light of the same types or the same styles of the same patient. Summation of the scores of interval change and duration change of the same type or the same style and 5 of basic score was the score of a corresponding seizure type or a corresponding style of one patient. In order to test its reliability and validity, the score of change of frequency or duration plus 5 scores respectively was the score of frequency or duration. ② Reliability and validity were tested by calculating corresponding correlation coefficient with SPSS 11.0. ROC curve was used for developing diagnostic criterion of predicting therapeutic effects with SPSS 11.0. MAIN OUTCOME MEASURES： ① Reliability and validity; ② Diagnostic criterion for predicting therapeutic effects one year later. RESULTS： Totally 28 patients were involved in the final analysis of results. ① Reliability and validity were high：rinter-rater=0.98, rtest-retest=0.99, rconstruct validity=0.83. ② A total score 〉 6 was the optimal diagnostic criteria for predicting therapeutic effects one year later, in other words, a patient who scored more than 6 at the evaluating period may be seizure-free one year later. CONCLUSION： It is a potential tool for evaluating epileptic therapeutic outcome, and it can be diffusely used in interrelated fields after being further validated.

Clinical effectiveness of adding probiotics to a low FODMAP diet:Randomized double-blind placebo-controlled study

BACKGROUND There are various studies showing the relationship between irritable bowel syndrome(IBS)and diet,and some dietary adjustments are recommended to reduce symptoms.In recent years,there is a growing number of studies that show a 4-8 wk low fermentable oligo,di-and mono-saccharides and polyols(FODMAP)diet has a 50%-80%significant effect on symptoms in IBS patients.There is strong evidence suggesting that changes in fecal microbiota have an impact on IBS pathogenesis.Based on this argument,probiotics have been used in IBS treatment for a long time.As is seen,the FODMAP diet and probiotics are used separately in IBS treatment.AIM To evaluate the effectiveness of adding probiotics to a low FODMAP diet to control the symptoms in patients with IBS.METHODS The patients who were admitted to the Gastroenterology Clinic of Dokuz Eylul University Hospital and diagnosed with IBS according to Rome IV criteria were enrolled into the study.They were randomized into 2 groups each of which consisted of 50 patients.All patients were referred to a dietitian to receive dietary recommendations for the low FODMAP diet with a daily intake of 9 g.The patients were asked to keep a diary of foods and beverages they consumed.The patients in Group 1 were given supplementary food containing probiotics(2 g)once a day in addition to their low FODMAP diet,while the patients in Group 2 were given a placebo once a day in addition to their low FODMAP diet.Visual analogue scale(VAS),the Bristol Stool Scale and IBS Symptom Severity Scale(IBSSSS)scores were evaluated before and after the 21 d treatment.RESULTS The rate of adherence of 85 patients,who completed the study,to the FODMAP restricted diet was 92%,being 90%in Group 1 and 94%in Group 2.The mean scores of VAS and IBS-SSS of the patients in Group 1 before treatment were 4.6±2.7 and 310.0±78.4,respectively,and these scores decreased to 2.0±1.9 and 172.0±93.0 after treatment(both P<0.001).The mean VAS and IBS-SSS scores of the patients in Group 2 before treatment were 4.7±2.7 and 317.0±87.5,respectively,and these scores decreased to 1.8±2.0 and 175.0±97.7 after treatment(both P<0.001).The IBS-SSS score of 37 patients(86.04%)in Group 1 and 36 patients(85.71%)in Group 2 decreased by more than 50 points.Group 1 and Group 2 were similar in terms of differences in VAS and IBS-SSS scores before and after treatment.When changes in stool shape after treatment were compared using the Bristol Stool Scale,both groups showed significant change.CONCLUSION This study is the randomized controlled study to examine the efficiency of probiotic supplementation to a low FODMAP diet in all subtypes of IBS.The low FODMAP diet has highly positive effects on symptoms of all subtypes of IBS.It was seen that adding probiotics to a low FODMAP diet does not make an additional contribution to symptom response and adherence to the diet.

Evaluation of the scales assessing the severity of myasthenia gravis

Objective To evaluate the reliability and validity of the 4 myasthenia gravis(MG)scales widely used for assessing the grades of disease severity in Chinese MG patients.Methods Sixty MG patients were examined by a neurologist with the following four MG scales:Quantitative Myasthenia Gravis Score(QMGS),Myasthenia Gravis Composite(MGC),Myasthenic Muscle Scale(MMS),Absolute and Relative Score of MG(ARS-

Clinical, brain electric earth map, endothelin and transcranial ultrasonic Doppler findings after hyperbaric oxygen treatment for severe brain injury

目的 探讨高压氧治疗重型颅脑损伤的疗效及机制。方法 重型颅脑损伤患者 35例为治疗组 ,2 0例为对照组 ,观察高压氧治疗前后临床 (GCS)、脑电地形图 (BEAM)、血内皮素 (ET)、经颅多普勒超声 (TCD)及预后 (GOS)的变化。结果 治疗组患者经高压氧治疗后临床 (GCS)、脑电地形图及预后均明显改善 ,与对照组相比有统计学意义。高压氧治疗 1个疗程后 ,治疗组血内皮素由 91 2 4± 12 18ng/L下降到 6 8 88± 14 37ng/L(P <0 0 1) ;经颅多普勒超声示大脑中动脉Vm也由 6 4 2± 4 8cm/s下降到 51 6± 4 2cm/s(P <0 0 1) ;同时 ,大脑中动脉VsPI也明显下降。统计学有显著性意义 (P <0 0 1)。结论 高压氧治疗能够明显改善重型颅脑损伤患者的临床、脑电地形图及预后 ,并且通过降低急性期血内皮素、改善大脑中动脉血流速度及血管阻力来改善重型颅脑损伤后脑血管痉挛及脑缺血缺氧。同时 ,降低颅内压是高压氧治疗重度颅脑损伤的重要机制之一。

Efficacy of Saam acupuncture treatment on improvement of immune cell numbers in cancer patients:a pilot study

OBJECTIVE: To collect preliminary data on the effects of Saam acupuncture with regard to the immunity in cancer patients.METHODS: Ten cancer patients were analyzed for improvements in immunity. Acupuncture was applied at the 5 acupuncture points, Jingqu(LU 8), Zutonggu(BL 66), Yanggu(SI 5), Yangchi(TE 4), and Zhongwan(CV 12) for 2 weeks with 4 sessions. We assessed the effect of Korean Saam acupuncture on the immune system in cancer patients by measuring particular blood cell subsets, including CD3 +,CD4+, CD8+, CD19+, and CD56+ cells, as well as total white blood cell count, absolute neutrophil count, and fatigue score. The measurement was performed before and after acupuncture and at a 2-week follow-up.RESULTS: There was a statistically significant increase in the number of CD3+(P=0.023) and CD8+ cells(P<0.001) and T-cell subsets, as well as a decrease in the fatigue severity scale(FSS) score(P=0.001) after Saam acupuncture using the 5 acupoints.CONCLUSION: Acupuncture may improve the immune system by increasing the counts of a few immune cells and relieve fatigue in cancer patients by decreasing FSS scores. Although this was a non-controlled study, it constitutes preliminary research investigating the potential effects of Saam acupuncture in increasing the counts of several immune cells in cancer patients.

Clinical Research into Qufeng Zhidong Recipe Used to Treat 31 Children with Tic Disorder

Objective: To assess the therapeutic effect and adverse reaction of Qufeng Zhidong Recipe (a recipe for dispelling wind to stop abnormal movement) used to treat children with tic disorder (TD). Methods: The enrolled patients were randomized into a TCM group (31 cases) treated with Qufeng Zhidong Recipe and a Western medicine group (30 cases) treated with haloperidol and trihexyphenidyl. Two courses of treatment were observed with 12 weeks as one course. The therapeutic effect and adverse reaction were assessed with Yale Global Tic Severity Scale (YGTSS), Tic Symptom Score Scale (TSSS), TCM Syndrome Score Scale (TCMSSS), Treatment Emergent Symptom Scale (TESS) and laboratory examinations. Results: The total effective rate was 100% in the TCM group and 60% in the Western medicine group with statistical significance in difference (P<0.05). All the scores in the TCM group were better than those in the Western medicine group (P<0.05). Conclusion: Qufeng Zhidong Recipe can obviously relieve the symptoms and signs of TD children without toxic side-effects.