Cognitive Safety and Overall Tolerability of Imidafenacin in Clinical Use: A Long-Term, Open-Label, Post-Marketing Surveillance Study.

OBJECTIVES: To assess the effect of imidafenacin on cognitive function, including the conversion rate of mild cognitive impairment (MCI) to dementia, in a period of one year. METHODS: Patients newly administered imidafenacin to treat overactive bladder (OAB), including those who had MCI or dementia, were surveyed across Japan (cognitive safety analysis set [CSAS]), on all of whom we performed the Mini-Mental State Examination (MMSE) at baseline, 24- and 48-weeks after treatment. From CSAS, we extracted well described cases of OAB change as well as drug-related adverse events of dry mouth etc. (efficacy analysis set [EAS]). From CSAS, we extracted MCI cases (MCI set [MCIS]) to analyze the conversion rate of MCI to dementia. MCI is defined by exclusion of normal individual and apparent dementia. RESULTS: The cognitive safety analysis set comprised 187 patients who were collected from 51 medical institutions, and no significant decrease was noted in the MMSE scores in the patients during follow-up. EAS comprised 176 patients. In this group, drug-related adverse events such as dry mouth were reported in 15 (8.5%). MCIS comprised 145 patients. In this group, the annual conversion rate of MCI to dementia was 3.6%, and this rate did not exceed those reported in past epidemiological studies (6.8-16.1% per year). CONCLUSIONS: The present findings suggest that imidafenacin can be used safely for cognitively vulnerable patients with OAB.

Spontaneous platelet aggregation in normal subject assessed by a laser light scattering method: an attempt at standardization.

Platelet aggregometry by the laser light scattering (LS) method is sufficiently sensitive to detect small platelet aggregates that form spontaneously in vitro in the absence of agonists. Platelet aggregation without agonists is named spontaneous platelet aggregation (SPA). Since SPA has been suggested to be associated with various thrombotic diseases, it is essential to measure SPA and to establish a standard range of SPA values. In this study, we measured SPA in 167 healthy subjects by the LS method and attempted to clarify various factors influencing SPA, including the blood collection procedure. We also attempted to establish a tentative standard range of SPA values. SPA was quantitatively measured in terms of the maximum total LS intensity, which reflects small aggregates formed over 10 minutes (SMAX) and the area under the total LS intensity curve of small aggregates (SAUC). Since both the values of SMAX and SAUC were skewed and the log SMAX and log AUC values showed a normal distribution, the statistical analyses were performed using log SMAX and log SAUC. The log SMAX and log SAUC were significantly higher in the samples collected using a tourniquet and/or a 21 G needle, than in those collected without a tourniquet and/or with an 18 G needle. The log SAUC values were significantly lower in samples obtained with a syringe and/or 3.8% sodium citrate than in those obtained in vacuum sampling tubes and/or 3.13% or 3.14% sodium citrate. The Ht and plasma glucose concentration influenced the log SMAX values. We propose that to standardize SPA measurements, the measurements should be completed within two hours of blood sample collection and collected using the regular concentration of citrate. The standard range of SMAX values measured in samples obtained using a tourniquet and a 21 G needle was 2.0-23.99 (*10(3) mV*count). The standard range of SAUC values measured under same conditions was 0.58-9.12 (*10(6) mV*count*min). The standard range of SMAX values measured in samples obtained using a tourniquet, 21 G needle and a vacuum tube was 1.7-29.51 (*10(3) mV*count). The standard range of SAUC values measured under same conditions was 0.59-9.33 (*10(6) mV*count*min).

[Very-long-chain acyl-CoA dehydrogenase deficiency presenting with recurrent rhabdomyolysis in an adult].

We report a 30-year-old man with very-long-chain acyl-coenzyme A deficiency presenting recurrent rhabdomyolysis. Since the age of 18-year-old, he had noticed recurrent episodes of exercise induced limb muscle pain, limb weakness and dark colored urine. At 29-year-old, he developed the same symptoms, and was referred to our hospital for further examinations under a diagnosis of recurrent rhabdomyolysis. He had no history of trauma, administration of drugs, infections and other factors causing rhabdomyolysis. There were no similar cases in his household. Neurological examinations on admission revealed no abnormal findings. Routine laboratory findings only showed mildly elevated levels of muscle-origin enzymes including CK and aldolase. Ischemic forearm exercise test showed normal levels of lactate and pyruvate in resting state, and normal response after exercise. Organic acids in urine at asymptomatic period were normal. Total carnitine and acyl-carnitine levels in serum were low. Electrospray tandem mass spectrometry in dried blood spots and serum identified elevated level of tetradecenoic acid (C14:1), and palmitoyl-CoA dehydrogenase activity of lymphocytes was deficient. Based on these data, we made a diagnosis of very-long-chain acyl-coenzyme A (VLCAD) deficiency in this patient. Several reports showed that muscular form (adult onset form) of VLCAD deficiency demonstrated recurrent rhabdomyolysis, but true 'adult-onset' case with VLCAD deficiency have been rarely reported. We emphasize that muscular form of VLCAD deficiency should be regarded as one of the causes of recurrent rhabdomyolysis in adult.

[Functional neural reorganization following ischemic stroke in the precentral knob: an fMRI study].

We evaluated a 63 year-old, right-handed woman by functional MRI (fMRI) in the early and the recovery stages following a cerebral infarction in the right precentral knob. An activated signal in the ipsilateral sensorimotor cortex and contralateral supplementary motor cortex during deteriorated hand grasping (left) was observed in the early stages, whereas being unable to detect in the functionally recovered period. When simultaneous bilateral hand grasping was performed, the activated signal around infarct region was enlarged in recovered period. The functionally neural reorganization processes relating recovered hand movement after localized cortical infarction (precentral knob) was suggested.