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).     

Gastric volvulus and giant Bochdalek hernia in an adult patient that were safely repaired by endoscopic reduction and elective laparoscopic surgery

A Bochdalek hernia (BH) is a congenital abnormality with incomplete closure of the diaphragm. It is usually manifested in infants but rarely in adults. Here, we report an adult patient with gastric volvulus and giant BH that were safely repaired by endoscopic reduction and elective laparoscopic surgery, respectively. A 79-year-old woman presented with left upper abdominal pain but no history of trauma. CT revealed a giant BH with gastric volvulus. After emergency endoscopic reduction of the volvulus, elective laparoscopic repair of the BH was performed. The 8 × 8-cm defect was repaired with interrupted nonabsorbable sutures and a mesh. The patient's postoperative course was uneventful, and no complications or recurrence were observed in the 6 months that followed.     

Dermoscopic features of hidroacanthoma simplex: Usefulness in distinguishing it from Bowen's disease and seborrheic keratosis

Hidroacanthoma simplex (HAS) is a rare benign eccrine adnexal tumor. HAS is sometimes clinically or pathologically misdiagnosed as squamous cell carcinoma in situ (Bowen's disease; BD), seborrheic keratosis (SK) or other adnexal tumor. To date, there has never been a report focusing on dermoscopic features to distinguish HAS from BD and SK. We found the following dermoscopic findings to be characteristic of HAS: fine black dots/globules (75% of cases) and fine scales arranged annularly (100% of cases). In contrast, glomerular vessels, which are typically observed in BD, were not seen in any of the four cases. Cerebriform appearance and milia‐like cysts, which are typically observed in SK, were also not seen in any of the four cases. The existence of “scattered fine black dots/globules” and “fine scales arranged annularly”, and the absence of the glomerular vessels, may contribute to precise diagnosis of HAS. Even though HAS resembles BD or SK clinically, it can be distinguished from these by the characteristic dermoscopic features.     

Hepatic conversion of 1-(tetrahydro-2-furanyl)-5-fluorouracil into 5-fluorouracil in patients with hepatocellular carcinoma

The pharmacokinetics of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) and its conversion into 5-fluorouracil (FUra) in liver tissue were studied in ten patients with hepatocellular carcinoma (HCC). The plasma concentration of FT after its intravenous injection (dosage: 800 mg) was computerfitted to a bi-exponential function (C = Ae-alpha t + Be-beta t), indicating a two-compartment disposition. The pharmacokinetic parameters did not significantly differ between the five patients with, and the five without cirrhosis of the liver. The plasma concentrations of FUra likewise showed no significant difference between the two groups. The rates of FT degradation in the liver tissue homogenate were similar for four of the patients with cirrhosis (0.10 +/- 0.05 mumol/g liver protein/30 min) and four of those without it (0.13 +/- 0.05). The rates of cytochrome P-450-dependent FUra formation in the microsomal fraction of liver tissue from two patients (1.1 and 1.3 nmol/mg microsomal protein/30 min) were dramatically reduced to less than half of those of two control subjects (2.4 and 2.7). The estimated rates of FUra formation in the soluble fraction (105,000 X g supernatant fraction) from the two patients (0.1 and 0.13 nmol/mg protein/30 min) were almost identical to those from the controls (0.12 and 0.14), suggesting that the rate in the soluble fraction from HCC patients may not be as strongly affected as the rate in the microsomal fraction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recovery functions of somatosensory vertex potentials in man: interaction of evoked responses from right and left fingers.

Somatosensory vertex potentials (SVPs) were examined in 12 healthy subjects in response to painful electrical stimulation of the finger. SVPs consisted of N1, P1, and N2. The average latencies of the 3 peaks were 150, 225, and 350 msec, respectively. The latency and amplitude of each potential were reproducible for each subject. Recovery functions of the SVPs were analyzed in 10 subjects. A pair of stimuli were delivered to the right or left finger with interstimulus intervals (ISIs) of 50, 100, 150, 200, 350, 500 and 650 msec. SVPs partially recovered with the shortest ISI (50 msec). Full recovery could not be obtained even with the longest ISI (650 msec). Differences in recoveries within 650 msec of ISI were not observed between right and left stimulations. To examine the interaction between SVPs evoked by right and left finger stimulation, recovery functions from prior contralateral finger stimulation were analyzed with the same ISIs. SVP recoveries for right after left or left after right patterns of stimulus delivery were nearly the same as those for ipsilateral ones. It is suggested that SVPs are generated at nearly the same site in the sensory pathway regardless of the side stimulated.     

Comparative study of the bacterial flora in both uterocervical and uterine regions

The relationship between indigenous bacterial floras in the lower genitals and the uterocervical region is of importance due to a barrier-like role against ascending infections through the mechanism of the localized protection at a boundary of the uterocervical region. Therefore, bacterial flora in the uterocervical and uterine regions was studied in cases for which gynecological operations were performed (n = 77). 1. Ratios of incidences of the detection of bacteria on the uterocervical and in the uterine regions were 50/77 (64.9%) and 6/77 (7.8%), respectively. When different age groups are compared, the detection ratio from the uterocervical region was high among patients in the 40 s, and all the cases in which bacteria were detected from the uterine region were in the 40 s. 2. Gram-positive bacteria were detected at a high ratio, and anaerobic bacteria were noted in the uterocervical region, and ratios of detection of Staphylococcus epidermidis, Lactobacillus sp. and Propionibacterium acnes were high. Six strains of Gram-positive bacteria and 1 strain of Candida sp. were noted in the uterine region. 3. When cefmetazole (CMZ) was administered for the prevention of the infections after these panhysterectomy cases examined here, no postoperative infectious diseases nor adverse reactions were noted.     

Resected cases of middle lobe primary cancer

Of 200 lung cancer lesions resected in our hospital, there were 15 cases (7.5%) with middle lobe origin. The histological types were adenocarcinoma in 13 patients (4 patients with alveolar cell carcinoma), squamous cell carcinoma in one and large cell carcinoma in one. These patients were classified into two groups according to the type of operation they received and each group was evaluated. Group I (resection of the middle lobe) included 8 patients. Each one of Stage IIIB and Stage IV received the operation to improve their symptoms. The six patients of Stage I received only middle lobectomy as absolute curable cases. Group II (resection of the middle and lower lobes) included 7 patients, who had preoperative diagnosis of stage III. Two of them were postoperatively found to be cases of Stage I and Stage II. Although it was still short-term, the follow-up evaluation proved that these patients survived without local recurrence and distant metastasis, except for two with pleural dissemination and one with cerebral metastasis, who had received lobectomy as palliative operation. No difference was observed between the two groups receiving different types of operation.     

The kapurimycins, new antitumor antibiotics produced by Streptomyces. Physico-chemical properties and structure determination

The kapurimycins A1, A2 and A3 were revealed to be new antitumor antibiotics with molecular formula of C27H26O9, C26H24O9 and C27H24O9, respectively. The structures of the kapurimycins were determined by NMR spectroscopic analysis. The kapurimycins are new class of polycyclic microbial metabolites having the tetrahydroanthra-gamma-pyrone skeleton and the beta, gamma-unsaturated delta-keto carboxylic acid structure. The individual components of the kapurimycins differ from one another in the side chain at the pyrone ring of the molecule.