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).     

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.     

In Vivo Molecular Imaging Characterizes Pulmonary Gene Expression During Experimental Lung Transplantation

Experimental gene therapy is a promising strategy to prevent ischemia-reperfusion (I/R) injury and allograft rejection after lung transplantation, and methods will eventually be needed to characterize pulmonary transgene expression in vivo in humans. Therefore, we studied positron emission tomography (PET) as a means of performing in vivo molecular imaging in rodent models of lung transplantation. Rats were transfected endotracheally with adenovirus encoding a fusion gene of a mutant Herpes simplex virus-1 thymidine kinase and the green fluorescent protein gene (the former serving as an imaging reporter gene). Twenty-four hours after transfection, lungs were transplanted in groups representing normal transplantation, I/R injury and acute allograft rejection. Imaging was obtained either 24 h after transplantation to study reperfusion injury or 4 days after transplantation to study graft rejection. After imaging, lungs were excised and analyzed for thymidine kinase activity. Imaging detected transgene expression in transplanted lungs even in the presence of acute rejection or I/R injury. The PET imaging signal correlated with in vitro lung tissue assays of thymidine kinase activity (r(2) = 0.534). Thus, noninvasive molecular imaging with PET is a feasible, sensitive and quantitative method for characterizing pulmonary transgene expression in experimental lung transplantation.     

Case of acute urinary retention as a result of non-steroidal anti-inflammatory drugs

Abstract:   A 19-year-old woman presented at our hospital with acute urinary retention in September 2005. She had experienced the same chief complaint twice previously. She had used non-steroidal anti-inflammatory drugs before acute urinary retention. The results of physical examinations were unremarkable, and her neurologic signs were not remarkable. The basic laboratory test values were all normal and a psychiatric assessment indicated that her symptoms were not psychogenic. Magnetic resonance imaging was carried out, but revealed only a slight bulging in the L3/L4/L5 disk. Water cystometry showed acontractile detrusor. We made a diagnosis of acute urinary retention as a result of non-steroidal anti-inflammatory drugs because of her use of such drugs before the development of symptoms on multiple occasions. This patient was regularly followed up as an outpatient, and she could void smoothly in February 2006. This is the first report which acute urinary retention associated with non-steroidal anti-inflammatory drugs in Japan.     

A case of idiopathic bronchiolitis obliterans accompanied with pneumothorax and pulmonary atypical mycobacteriosis]

A 22-year-old man was urgently admitted for pneumothorax. He continued complaining of exertional dyspnea and dry cough after the pneumothorax healed. About three months later, an atypical pulmonary mycobacteriosis by mycobacterium kansasii was identified. Exertional dyspnea increased after chemotherapy was administered, and the patient was readmitted because of difficulty in daily life activities. Chest radiographs and CT scans showed bilateral pulmonary hyperinflation and a narrowed heart shadow. There was also marked combined ventilatory impairment, as identified by a respiratory function test. Furthermore, the histological findings of surgically removed lung tissue revealed accumulation of lymphocytes in the wall of a small bronchus. Idiopathic bronchiolitis obliterans was diagnosed from the clinical course and clinical findings. The patient is now being monitored and is awaiting lung transplantation.     

Differential effects of isoproterenol on the canine atrial action potential in the presence of carbachol or nicorandil

In canine atrial muscles, carbachol and nicorandil hyperpolarized the resting membrane potential and shortened the action potential duration. In the presence of carbachol or nicorandil, isoproterenol further hyperpolarized the resting membrane potential and shortened the action potential duration. Isoproterenol significantly increased the plateau duration in the presence of nicorandil, but further abbreviated it in the presence of carbachol. This increase in the plateau duration by isoproterenol in the presence of nicorandil probably reflects the increase in the slow inward current.