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).     

Pharynx and oesophagus evaluation during the swallow using helical computerized tomography.

PURPOSE: Videofluorography (VF) and endoscopy are commonly used for dynamic imaging (DI) of pharyngeal swallowing but do not offer transverse plane (TP) information. The aim of the present study was to evaluate helical computerized tomography (HCT) to measure the DI capability pharyngeal swallowing in the TP. METHODS: The HCT scan technique used was a single-slice cine mode with scan times of 100 ms. All 15 subjects were studied supine during dry swallow, swallowing of barium sulphate jelly and 3, 10, 15 or 20 ml of a 40% barium sulphate solution. Nine subjects repeated the test twice at more than 1 week's interval to determine the test-retest reliability. RESULTS: Swallowing leads to closure of the vocal folds, pharyngeal constriction and narrowing of the piriform sinuses allowing jelly passage between the sinuses. Laryngeal elevation then occurs with the opening of the pharyngoesophageal segment (PES). Swallowing a bolus of 20 ml produced the maximum anteroposterior and transverse diameters as well as the maximum opening area of the PES. The test-retest intraclass correlation coefficients with liquid deglutition ranged from 0.86 to 0.98. CONCLUSIONS: This study shows that HCT enables visualization of TP of PES complementing VF or endoscopic swallowing studies.     

P31 The relationship between the relative amount of Porphyromonas gingivalis in saliva and halitosis

Objectives  Porphyromonas gingivalis is one of the microorganisms that most actively produce CH₃SH and we have reported that subjects with P . gingivalis have higher CH₃SH levels than subjects without P .  gingivalis . However, little is known about the relationship between P . gingivalis levels in saliva and the condition of oral malodor. In this study, we evaluated the association between the relative amount of P . gingivalis in saliva and halitosis in mouth air.
Methods  All of the subjects were patients at the Preventive Dentistry and Breath Odor Clinic of Kyushu Dental College, where they received a periodontal examination. Volatile sulfur compounds (VSC: hydrogen sulfide and methyl mercaptan) were measured using gas chromatography. Saliva samples were collected in a sterile plastic tube over a period of 5 min while the subject chewed on paraffin wax, and were then immediately stored at –80°C until use. Template DNA was obtained from the stored saliva using an Easy-DNA Kit (Invitrogen, CA, USA) according to the manufacturer's instructions. Conventional PCR assays were used to confirm the presence of P . gingivalis . A 5' nuclease TaqMan PCR was used to quantify P . gingivalis in saliva. The relative numbers of bacteria were measured using the comparative threshold cycle method.
Results  We found a quantitative relationship between the P . gingivalis levels in saliva and the condition of halitosis in mouth air.
Conclusion  We analyzed the relationship between the relative amount of P . gingivalis in saliva and oral malodor.     

Retroperitoneal primary mucinous adenocarcinoma with a mural nodule of anaplastic tumor: a case report and literature review.

A 38-year-old female presented with a lower abdominal mass. During the operation the mass was found to be retroperitoneal and was excised. Gross examination revealed a mucin-containing cystic lesion with a mural nodule. On microscopic examination, the cystic areas were lined by an invasive mucinous adenocarcinoma and the nodule was composed of an anaplastic sarcomatoid tumor that was immunoreactive for cytokeratin. This present case is the 21st example of a retroperitoneal primary mucinous cystadenocarcinoma and the fourth with a mural nodule. Three of four cases with a mural nodule, including our case, had a rapidly fatal outcome.     

Implications of Popliteal Lymph Node Detected by Sentinel Lymph Node Biopsy

BACKGROUND: Although there is lymphatic flow into the popliteal fossa from a skin tumor located in the lower leg, popliteal metastasis is extremely rare. Recently, sentinel lymph nodes outside traditional nodal basins have been identified. This study investigated the incidence of sentinel nodes in the popliteal region and the indication for biopsy. METHODS: Fourteen patients with various skin cancers involving the lower extremities (nine melanomas, four squamous cell carcinomas, and one sweat gland carcinoma) underwent lymphoscintigraphy and excision with sentinel lymph node biopsy. RESULTS: In all 14 patients, hot spots showed accumulation in the groin region. Five of 14 patients (36%) demonstrated popliteal sentinel nodes in addition to the inguinal nodes. Three of five popliteal sentinel nodes were histologically studied. A patient with acral melanoma demonstrated micrometastasis of melanoma cells in a popliteal node but not in the groin node. CONCLUSION: This study demonstrates that sentinel lymph nodes located in the popliteal fossa are frequently detected by lymphoscintigraphy and that biopsy should be performed if popliteal nodes are identified.     

Prevention of Acute Lung Allograft Rejection in Rat by CTLA4Ig

CTLA4 immunoglobulin (CTLA4Ig), which binds with a high affinity to B7-1 and B7-2, interrupts T-cell activation by inhibiting costimulatory signal. CTLA4Ig has been used in hopes of achieving antigen-specific tolerance induction in several solid organ transplants. In lung allograft rejection, however, its use has been controversial in terms of its effect on prevention of rejection. In the present study, the effect of murine CTLA4Ig on rat-lung allograft rejection was investigated. Rat left-lung transplantation was performed in an RT1 incompatible donor (Brown Norway; BN)-recipient (F344) combination. All allografts (n = 12) without any treatment were rejected within 7 days after transplantation. A single injection of murine form CTLA41g at a dose of 100 microg intraperitoneally (ip) or intravenously (iv) on day 1 post-transplantation achieved long-term graft survival (>90days) in 2/5 (40%) and 3/8 (38%), respectively. Moreover, 6/7 (86%) allografts in rats that received iv injection of 500 microg CTLA4Ig survived more than 90days. Allograft survival in the CTLA4Ig 500 microg iv recipient group was significantly longer than that in the no-treatment control or control immunoglobulin group (p <0.01). Four out of seven recipients bearing functional allografts for more than 90 days with the CTLA4Ig treatment accepted donor-specific skin grafts, whereas all third-party skin grafts (n=3) were rejected. Prevention of rat-lung allograft rejection could be achieved by intravenous administration of CTLA4Ig, resulting in long-term allograft survival with acceptance of donor-specific skin grafts.     

Optic nerve injury demonstrated by MRI with STIR sequences

We studied nine patients with optic nerve injury associated with closed head trauma by magnetic resonance imaging (MRI) with short inversion time inversion recovery (STIR) sequences on 11 occasions from 4 days to 14 years after the injury: three studies were within 17 days and eight over 4 months to 14 years. MRI revealed abnormal high signal in 10 of the 11 injured nerves. MRI 4 days after the injury showed no abnormality.