Efficacy of istradefylline for gait disorders with freezing of gait in Parkinson’s disease: A single-arm,open-label,prospective, multicenter study

Background: Gait disorders are common in Parkinson’s disease patients who respond poorly to dopaminergic treatment. Blockade of adenosine A_2A receptors is expected to improve gait disorders. Istradefylline is a first-in-class selective adenosine A_2A receptor antagonist with benefits for motor complications associated with Parkinson’s disease.

Research design and methods: This multicenter, open-label, single-group, prospective interventional study evaluated changes in total gait-related scores of the Part II/III Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Freezing of Gait Questionnaire (FOG-Q) in 31 Parkinson’s disease patients treated with istradefylline. Gait analysis by portable gait rhythmogram was performed.

Results: MDS-UPDRS Part III gait-related total scores significantly decreased at Weeks 4–12 from baseline with significant improvements in gait, freezing of gait, and postural stability. Significant decreases in MDS-UPDRS Part II total scores and individual item scores at Week 12 indicated improved daily living activities. At Week 12, there were significant improvements in FOG-Q, new FOG-Q, and overall movement per 48 h measured by portable gait rhythmogram. Adverse events occurred in 7/31 patients.

Conclusions: Istradefylline improved gait disorders in Parkinson’s disease patients complicated with freezing of gait, improving their quality of life. No unexpected adverse drug reactions were identified.

Trial registration: UMIN-CTR (UMIN000020288).     

Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.     

Potassium excretion in healthy Japanese women was increased by a dietary intervention utilizing home-parcel delivery of Okinawan vegetables.

Potassium, which is abundant in vegetables, is inversely related to blood pressure. Although the situation has changed somewhat in recent years, the Okinawan diet has generally included a large amount of vegetables, and until recently Okinawans had the lowest rates of mortality due to stroke and coronary heart disease in Japan. Based on the hypothesis that these low mortality rates are partly attributable to increased potassium intake resulting from the high vegetable consumption, this study examined whether increasing the consumption of typical yellow-green Okinawan vegetables increases potassium intake. The purpose of this investigation was to determine whether increased consumption of these vegetables should be one of the dietary modifications recommended in public health promotion programs for Okinawans. The study employed 56 healthy, normotensive, free-living Japanese women aged 18-38 years living in Okinawa. They were randomized to a dietary intervention group (n=27) or a control group (n=29). Members of the dietary intervention group received an average weight of 371.4 g/day of a combination of the following vegetables twice weekly through an express home parcel deliver service for a period of 14 days: Goya (Momordica charantia), green papaya (Carica papaya), Handama (Gynura bicolor), Karashina (Brassica juncea), Njana (Crepidiastrum lanceolatium), Fuchiba (Artemisia vulgaris) and Fudanso (Beta vulgaris); and they consumed an average of 144.9 g/day, resulting in a 20.5% increase in their urinary potassium excretion over the baseline (p=0.045). The members of the control group were asked to avoid these vegetables, and the change in potassium excretion in this group was not significant (p=0.595). Urinary sodium and magnesium excretions, systolic and diastolic blood pressures, folic acid, triglycerides and serum high density lipoprotein cholesterol, low density lipoprotein cholesterol and total cholesterols changed non-significantly in both groups. Also, post-intervention urinary potassium excretion correlated positively with vegetable consumption in both the dietary intervention (p<0.0001) and control (p=0.008) groups and with Okinawan vegetable intake in the dietary intervention group (p=0.0004).     

Severe Graves' ophthalmopathy accompanied by myasthenia gravis]

We report a 53-year-old woman with severe Graves' ophthalmopathy accompanied by uncontrolled myasthenia gravis. She presented remarkable exophthalmos, chemosis, and restriction of eye movement. Despite plasma exchange, steroid pulse therapy, local injection of steroid, and irradiation, ocular symptoms did not ameliorate. Since optic neuropathy was seen, orbital decompression surgery was performed in the left eye. Bilateral chemosis was improved after the surgery. Five years after surgery, there was no ocular palsy in the operated left eye, but in the contralateral eye. For the good prognosis of the eye movement, orbital decompression might be recommended in the severe Graves' ophthalmopathy accompanied by the optic neuropathy and/or ophthalmoplegia with proptosis.     

A case of recurrent biliary cystadenocarcinoma successfully treated with 5FU/CDDP systemic chemotherapy]

We report a case of biliary cystadenocarcinoma which recurred 41 months postoperatively. A 60-year-old woman was admitted for further examination of multiple metastatic tumors and a large amount of ascites. Systemic administration of 5FU and CDDP caused her CEA level to decrease gradually and abdominal computed tomography revealed considerable reduction of the metastatic tumors and ascites. Since her general condition had improved, chemotherapy was continued in the outpatient clinic.     

A sewing needle completely buried in the myocardium removed under extracorporeal circulation.

A 14-year-old boy had a needle accidentally inserted through his chest wall. Chest X-ray showed a needle-shaped metallic density localized in the cardiac silhouette. An echocardiography indicated the needle had passed through the interventricular septum, and its eye and point had reached the right and left ventricle, respectively. Surgical removal of the needle was performed. The needle could not be observed from the heart surface, and was recognized in a dent 5 mm on the right side from the left anterior descending branch (LAD). The needle was easily removed under extracorporeal circulation, and he was discharged ten days after the operation.     

IS THERE A SPECIFIC LINKAGE BETWEEN OBSTRUCTIVE SLEEP APNEA SYNDROME AND GASTROESOPHAGEAL REFLUX DISEASE?

Obstructive sleep apnea syndrome (OSAS) is a common condition characterized by repetitive sleep‐induced collapse of the upper airways. It is associated with increased risk for hypertension, ischemic heart disease, cerebral stroke, and traffic accidents. In contrast, gastroesophageal reflux disease (GERD) is a very common disorder defined as various symptoms or esophageal mucosal damage generated by the abnormal reflux of gastric contents into the esophagus. Patients with OSAS have been reported to have a high prevalence of gastroesophageal reflux (GER) symptoms. The increase of transdiaphragmatic pressure in parallel with the large negative intrathoracic pressure produced during apnea events may directly lead to GER. In addition, some studies have demonstrated improvement in GERD with the application of continuous positive airway pressure, most consistently effective treatment for OSAS. However, GER dose not occur with every apnea. Moreover, the common conditions observed in patients with OSAS, including obesity or alcohol ingestion, are also predisposing factors for GER. A more recent investigation in over 1000 subjects failed to show a causal link between both diseases. Thus, the potential relationship between OSAS and GERD remains controversial. Inconsistencies in definitions of both diseases or sampling biases may contribute to the confusing results.