Increased stiffness in common carotid artery in hyperthyroid Graves' disease patients.

The present study was undertaken to assess the effect of hyperthyroidism on stiffness in the common carotid artery (CCA) in patients with Graves' disease (GD) and elucidate the mechanism by which arterial stiffness is increased in hyperthyroidism. The arterial stiffness index beta (stiffness beta) was evaluated in the CCA using an ultrasonic phase-locked echo-tracking system. Stiffness beta was defined as the logarithm of the ratio of systolic to diastolic blood pressure divided by the fractional diameter increase during the cardiac cycle and thus established as a measure of arterial stiffness uninfluenced by the change in blood pressure. Seventy euthyroid GD patients were measured for CCA stiffness beta to determine its relationship to retinal blood flow and plasma levels of vascular injury markers. To investigate the effect of hyperthyroidism, 27 GD patients were measured for changes during antithyroid drug (ATD) therapy in stiffness beta and in hemodynamic parameters, retinal blood flow and plasma vascular injury markers. In euthyroid GD patients, stiffness beta in the CCA showed a significant and positive correlation with systolic blood pressure and pulse pressure, but not with peripheral blood flow in the central retinal artery. ATD therapy significantly reduced stiffness beta from 5.23 +/- 2.10 to 4.36 +/- 1.48. The fractional reduction of stiffness beta during ATD therapy correlated significantly with reductions in pulse pressure and retinal blood flow, but not with the reductions in systolic and mean blood pressure, or any of the plasma injury markers. In summary, the significant increase in stiffness beta in the hyperthyroid state may reflect the harmful effect of hyperthyroidism on the arterial wall, which may in turn result from increased stroke volume.     

A case of an epithelioid glioblastoma with the BRAF V600E mutation colocalized with BRAF intact low‐grade diffuse astrocytoma

Epithelioid glioblastomas are one of the rarest histological variants of glioblastomas, which are not formally recognized by the World Health Organization (WHO) classification. Epithelioid glioblastomas usually occur as primary lesions, but there have been several reports of secondary epithelioid glioblastomas or epithelioid glioblastomas with pre‐ or co‐existing lesions to date. The serine/threonine‐protein kinase B‐Raf (BRAF) V600E mutation has been found at a high frequency of 54% in epithelioid glioblastomas. We present a case of a 26‐year‐old female patient with an epithelioid glioblastoma with the BRAF V600E mutation in her right frontal lobe. In the present case, a low‐grade diffuse astrocytoma component had colocalized with the epithelioid glioblastoma. The component presented prominent calcification on neuroimages as well as by histology, and low‐grade diffuse astrocytoma was considered to be a precursor lesion of an epithelioid glioblastoma. However, the BRAF V600E mutation was detected only in epithelioid glioblastoma but not in low‐grade diffuse astrocytoma. To the best of our knowledge, this is the first report demonstrating a discrepancy in the BRAF V600E mutation states between epithelioid glioblastoma and colocalized low‐grade astrocytoma.     

Qualitative and quantitative abnormalities of argininosuccinate synthetase in citrullinemia

Enzymological and immunochemical analyses of the liver were preformed in seven Japanese patients with citrullinemia. Among the urea cycle enzymes in the liver, only the activity of argininosuccinate synthetase was specifically decreased to 2 to 50% of normal controls. Liver argininosuccinate synthetase of patients was indistinguishable from that of controls when tested immunochemically by Ouchterlony's double immunodiffusion technique with anti-rat argininosuccinate synthetase antiserum. Immunochemical analysis by means of the single radial immunodiffusion revealed that the decrease in the activity of liver argininosuccinate synthetase was explainable by a decrease in the amount of the enzyme protein in five patients, while the decrease in the activity in the other two patients was not accompanied by a decrease of enzyme protein. The Km values for the substrates of liver argininosuccinate synthetase of the former five were similar to those of the control, while the kinetic properties of the latter two were quite different in terms of higher Km values and negative cooperativity. From these results, we consider that citrullinemia may consist of more than one type including qualitative or quantitative abnormalities of argininosuccinate synthetase caused by some defects in certain genes or in the epigenetic processes in the liver.     

Treadmill training with body weight support: its effect on Parkinson's disease

OBJECTIVE: To test whether body weight-supported treadmill training (BWSTT) is effective in improving functional outcome of patients with Parkinson's disease. DESIGN: Prospective crossover trial. Patients were randomized to receive either a 4-week program of BWSTT with up to 20% of their body weight supported followed by 4 weeks of conventional physical therapy (PT), or the same treatments in the opposite order. Medications for parkinsonism were not modified throughout the study. SETTING: Inpatient rehabilitation unit for neurologic diseases. SUBJECTS: Ten patients (5 men, 5 women) with Hoehn and Yahr stage 2.5 or 3 parkinsonism; mean age 67.6 years, mean duration of Parkinson's disease 4.2 years. MAIN OUTCOME MEASURES: The Unified Parkinson's Disease Rating Scale (UPDRS), ambulation endurance and speed (sec/10 m), and number of steps for 10-meter walk. RESULTS: The mean total UPDRS before/after BWSTT was 31.6/25.6, and before/after PT was 29.1/28.0. Analysis of covariance for improvement of UPDRS demonstrated a significant effect of type of therapy (F(1, 16) = 42.779, p < .0001) but not order of therapy (F(1, 16) = 0.157, p = .697 1). Patients also had significantly greater improvement with BWSTT than with PT in ambulation speed (BWSTT, before/after = 10.0/8.3; PT, 9.5/8.9), and number of steps (BWSTT, 22.3/19.6; PT, 21.5/20.8). CONCLUSIONS: In persons with Parkinson's disease, treadmill training with body weight support produces greater improvement in activities of daily living, motor performance, and ambulation than does physical therapy.     

Long-term effect of body weight-supported treadmill training in Parkinson's disease: a randomized controlled trial

OBJECTIVE: To investigate whether body weight-supported treadmill training (BWSTT) is of long-term benefit for patients with Parkinson's disease (PD). DESIGN: Randomized controlled trial. SETTING: Inpatient rehabilitation unit for neurologic diseases in Japan. PARTICIPANTS: Twenty-four patients (Hoehn and Yahr stages 2.5 or 3) who were not demented (Mini-Mental State Examination score, >27). INTERVENTIONS: Patients were randomized to receive either a 45-minute session of BWSTT (up to 20% of body weight supported) or conventional physical therapy (PT) for 3 days a week for 1 month. MAIN OUTCOME MEASURES: Outcome measures were evaluated at baseline and at 1, 2, 3, and 6 months. Measures included the Unified Parkinson's Disease Rating Scale (UPDRS), ambulation speed (s/10 m), and number of steps taken for a 10-m walk as a parameter for stride length. RESULTS: Four patients needed modification of medications in the follow-up period. Twenty patients (BWSTT, n=11; PT, n=9) without modified medications were analyzed for functional outcome. Age, duration of PD, gender, and doses of medications were comparable. There was no difference in the baseline UPDRS (BWSTT=33.3; PT=32.6), speed (BWSTT=10.8; PT=11.5), and steps (BWSTT=23.4; PT=22.8). The BWSTT group had significantly greater improvement than the PT group (Mann-Whitney U test, Bonferroni adjustment for multiple comparison) in ambulation speed at 1 month (BWSTT=8.5; PT=10.8; P<.005); and in the number of steps at 1 (BWSTT=20.0; PT=22.7; P<.005), 2 (BWSTT=19.5; PT=22.4; P<.005), 3 (BWSTT=20.1; PT=23.1; P<.005), and 4 months (BWSTT=21.0; PT=23.0; P=.006). CONCLUSIONS: BWSTT has a lasting effect specifically on short-step gait in PD.