A Randomized Controlled Trial of Chinese Medicine on Nonmotor Symptoms in Parkinson's Disease.

Nonmotor symptoms (NMS) of Parkinson's disease (PD) have devastating impacts on both patients and their caregivers. Jiawei-Liujunzi Tang (JLT) has been used to treat some NMS of PD based on the Chinese medicine theory since Qing dynasty. Here we report a double-blind, randomized, placebo-controlled, add-on clinical trial aiming at evaluating the efficacy and safety of the JLT in treating NMS in PD patients. We randomly assigned 111 patients with idiopathic PD to receive either JLT or placebo for 32 weeks. Outcome measures were baseline to week 32 changes in Movement Disorder Society-Sponsored Revision of Unified PD Rating Scale (MDS-UPDRS) Parts I-IV and in NMS assessment scale for PD (NMSS). We observed improvements in the NMSS total score (p = 0.019), mood/cognition (p = 0.005), and reduction in hallucinations (p = 0.024). In addition, post hoc analysis showed a significant reduction in constipation (p < 0.001). However, there was no evidence of improvement in MDS-UPDRS Part I total score (p = 0.216) at week 32. Adverse events (AEs) were mild and comparable between the two groups. In conclusion, long-term administration of JLT is well tolerated and shows significant benefits in improving NMS including mood, cognition, and constipation.

Effect of chronic noise exposure on expression of N-methyl-D-aspartic acid receptor 2B and Tau phosphorylation in hippocampus of rats.

OBJECTIVE: To study the effect of chronic noise exposure on expression of N-methyl-D-aspartic acid receptor 2B (NR2B) and tau phosphorylation in hippocampus of rats. METHODS: Twenty-four male SD rats were divided in control group and chronic noise exposure group. NR2B expression and tau phosphorylation in hippocampus of rats were detected after chronic noise exposure (100 dB SPL white noise, 4 h/d×30d) and their mechanisms underlying neuronal apoptosis in hippocampus of rats with TUNEL staining. RESULTS: The NR2B expression decreased significantly after chronic noise exposure which resulted in tau hyperphosphorylation and neural apoptosis in hippocampus of rats. Immunohistochemistry showed that the tau hyperphosphorylation was most prominent in dentate gyrus (DG) and CA1 region of rat hippocampus. CONCLUSION: The abnormality of neurotransmitter system, especially Glu and NR2B containing NMDA receptor, and tau hyperphosphorylation in hippocampus of rats, may play a role in chronic noise-induced neural apoptosis and cognition impairment.

A Two-Stage Estimation Method for Random Coefficient Differential Equation Models with Application to Longitudinal HIV Dynamic Data.

We propose a two-stage estimation method for random coefficient ordinary differential equation (ODE) models. A maximum pseudo-likelihood estimator (MPLE) is derived based on a mixed-effects modeling approach and its asymptotic properties for population parameters are established. The proposed method does not require repeatedly solving ODEs, and is computationally efficient although it does pay a price with the loss of some estimation efficiency. However, the method does offer an alternative approach when the exact likelihood approach fails due to model complexity and high-dimensional parameter space, and it can also serve as a method to obtain the starting estimates for more accurate estimation methods. In addition, the proposed method does not need to specify the initial values of state variables and preserves all the advantages of the mixed-effects modeling approach. The finite sample properties of the proposed estimator are studied via Monte Carlo simulations and the methodology is also illustrated with application to an AIDS clinical data set.

Efficacy of a Chinese herbal proprietary medicine (Hemp Seed Pill) for functional constipation.

OBJECTIVES: Functional constipation (FC) is a common clinical complaint. Despite a lack of consolidated evidence, Chinese herbal medicine (CHM) has become a popular alternative treatment for this condition. The aim of this study was to assess, with a rigidly designed study, the efficacy and safety of a CHM proprietary medicine, Hemp Seed Pill (HSP), in optimal dosage for treating FC. METHODS: This study comprised two parts: trial I, a dose determination study, and trial II, a placebo-controlled clinical study. In trial I, the optimal dosage of HSP was first determined from among three doses (2.5, 5.0, and 7.5 g b.i.d.). In trial II, a randomized double-blind study, the efficacy and safety of HSP for FC patients (Rome III criteria) in excessive syndrome as defined by traditional Chinese medicine (TCM) theory were compared with placebo. All participants in trials underwent a 2-week run-in, an 8-week treatment, and an 8-week follow-up. The primary end point was the responder rate for complete spontaneous bowel movement (CSBM) during treatment. Participants with a mean increase of CSBM ≧ 1/week compared with their baselines were defined as responders. Secondary outcome measures included responder rate during follow-up, individual and global symptom assessments, and reported adverse effects (AEs). RESULTS: The dose of 7.5 g b.i.d. showed better therapeutic effect than that of 2.5 and 5.0 g b.i.d. among 96 subjects (32 per arm) in trial I and was therefore selected for comparison with placebo in trial II. In trial II, 120 subjects were randomized into two arms (60 per arm). Responder rates for the HSP and placebo groups were 43.3 and 8.3% during treatment and 30.0 and 15.0% in the follow-up period, respectively (P<0.05). Those in the HSP group showed benefit in terms of increased CSBM, relief in the severity of constipation and straining of evacuation, and effective reduction in the use of rescue therapy when compared with placebo. No serious AE was reported. CONCLUSIONS: HSP (7.5 g b.i.d.) is safe and effective for alleviating FC for subjects in excessive syndrome. Optimal dose determination may be crucial for all CHM studies.

[Treatment of focal bone defect in postoperative nonunion with autologous red bone marrow injection].

OBJECTIVE: To observe the clinical effect of autologous red bone marrow injection in treating focal bone defect in postoperative nonunion. METHODS: Thirteen patients with focal bone defect in postoperative nonunion (7 cases in tibia, 2 cases in femur, 4 cases in humerus), including 8 males and 5 females with the mean age of 32.5-years-old (ranging from 15 to 60 years). The bone defects were treated with autologous red bone marrow injection (1 time per 2 weeks, 5 times in total) and the X-rays of AP and LP were observed. RESULTS: Thirteen patients were followed up from 6 to 12 months with an average of 7.5 months. According to results of X-ray pictures, 13 cases obtained bone defect recovered completely, and the average time of union was 4 months. CONCLUSION: Autologous red bone marrow injection has ascendancy such as less wound and clear clinical effect, which can accelerate bone healing and promotes functional recovery of limb. It is a good method to treat focal bone defect in postoperative nonunion.

[Risk factors for capillary leak syndrome in children with tetralogy after operation].

OBJECTIVE: To determine risk factors of capillary leak syndrome(CLS) in children with tetralogy after operation. METHODS: Clinical data were retrospectively collected and analyzed from 32 tetralogy cases with CLS and 50 cases without CLS(control group), who received operation under cardiopulmonary bypass (CBP) in our hospital from October 2002 to December 2006. Risk factors with statistical significance were screened with univariate logistic regression analysis, independent risk factors of CLS were determined with multivariate logistic regression analysis. Postoperative outcome was compared between CLS group and control group. RESULT: Logistic analysis showed that the risk factors for CLS were age(OR=6.783), duration of CBP(OR=4.756)and MGoon index (OR=3.826). There were statistical differences in injection of colloid, time of inotropic drugs and ventilation between CLS and control groups(P<0.01). Eight CLS cases underwent peritoneal dialysis and 2 CLS cases died. CONCLUSION: The risk factors of CLS in children with tetralogy after CBP are age, duration of CBP and MGoon index.

[Clinical analysis of gastroesophageal reflux induced cough].

OBJECTIVE: To investigate the clinical features, diagnosis and management of gastroesophageal reflux induced cough (GERC). METHODS: The continuous ambulatory esophageal pH measurement was performed for 24 hour in 41 cases with chronic cough who had normal chest roentgenographic presentation, negative histamine provocation test and no abnormality of nasal cavity. The symptom association probability (SAP) was adopted to analyze the correlation of cough with gastroesophageal reflux. The anti-reflux treatment was given for 12 weeks to those patients with Demeester score >or= 14.72 and/or SAP >or= 75%. RESULTS: Twenty six out of 41 cases were diagnosed as patients with gastroesophageal reflux. The cough was completely cured in 12 cases after antireflux treatment. The SAP of cough in this cured group (proximal probe 0.75 +/- 0.21, distal probe 0.91 +/- 0.12, respectively) was significantly higher than that of patients who failed in response to antireflux treatment (proximal probe 0.36 +/- 0.31, distal probe 0.47 +/- 0.30, respectively, P < 0.05). CONCLUSION: The gastroesophageal reflux may be an independent factor which could induce chronic cough. Not only the frequency and severity of gastroesophageal reflux but also the SAP were helpful in making the diagnosis of GERC. Satisfied effect was achieved after sufficient anti-reflux treatment in patients with GERC.

[Clinical feature and airway inflammation in eosinophilic bronchitis].

OBJECTIVE: To study the clinical features and airway inflammation in eosinophilic bronchitis (EB) and the treatment outcomes. METHODS: Irwin's anatomic protocol for diagnosing chronic cough was used in 86 patients with chronic cough, and induced sputum by hypertonic saline aerosol inhalation was performed. Differential cell counts were performed in induced sputum, and eosinophilic cationic protein (ECP) was measured with fluoroimmunoassay, while interleukin-8 (IL-8) was measured with enzyme-linked absorbed immunoassay. EB was diagnosed according to Gibson's criteria and treated with inhaled budesonide 200 - 400 micro g twice daily for four weeks, and in some patients oral prednisone 10 - 15 mg/d or methyl-prednisone 8 - 12 mg/d was given for one week. RESULTS: 13 (15%) out of 86 patients with chronic cough were diagnosed as having EB. Dry cough was the major compliant and all had normal lung function with negative histamine provocation test. The Eos count was 0.1862 +/- 0.1632 and the concentration of ECP (2.53 +/- 2.07) mg/L in induced sputum were significant higher in patients with EB as compared with those normal subjects (P < 0.01). The cough disappeared in all patients at the end of one week of inhaled or orally administered corticosteroids. CONCLUSION: EB, an eosinophilic airway inflammation, is one of important causes of chronic cough and responds well to corticosteroid therapy.

[Etiological diagnosis of chronic cough with unknown causes].

OBJECTIVE: To explore the spectrum and frequency of causes for chronic cough in Chinese patients. METHODS: 86 patients with chronic cough were enrolled in the study. The diagnostic procedure was based on the anatomical protocol for diagnosing chronic cough designed by Irwin, and additional cytological assay was performed for sputum induced by hypertonic saline aerosol inhalation. The efficacy of therapy specific to the diagnosis was evaluated. RESULTS: Definite diagnosis was made in 77 (89.5%) out of the 86 patients with chronic cough. The most common causes included cough variant asthma (CVA) (24/86, 27.9%), postnasal drip syndrome (PNDs) (22/86, 25.6%), eosinophilic bronchitis (EB) (13/86, 15.1%), and gastroesophageal reflux (GER) (12/86, 14.0%). After active management based on the diagnosis, cough improved in 72 patients (93.5%). CONCLUSIONS: In addition to CVA, PNDs and GER, eosinophilic bronchitis is also an important cause of chronic cough. A positive response to the specific therapy is essential to a definite diagnosis.