Clinical characterization of patients with leucine-rich repeat kinase 2 genetic variants in Japan.

Variants of leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of familial Parkinson's disease (PD). We aimed to investigate the genetic and clinical features of patients with PD and LRRK2 variants in Japan by screening for LRRK2 variants in three exons (31, 41, and 48), which include the following pathogenic mutations: p.R1441C, p.R1441G, p.R1441H, p.G2019S, and p.I2020T. Herein, we obtained data containing LRRK2 variants derived from 1402 patients with PD (653 with sporadic PD and 749 with familial PD). As a result, we successfully detected pathogenic variants (four with p.R1441G, five with p.R1441H, seven with p.G2019S, and seven with p.I2020T) and other rare variants (two with p.V1447M, one with p.V1450I, one with p.T1491delT, and one with p.H2391Q). Two risk variants, p.P1446L and p.G2385R, were found in 10 and 146 patients, respectively. Most of the patients presented the symptoms resembling a common type of PD, such as middle-aged onset, tremor, akinesia, rigidity, and gait disturbance. Dysautonomia, cognitive decline, and psychosis were rarely observed. Each known pathogenic variant had a different founder in our cohort proven by haplotype analysis. The generation study revealed that the LRRK2 variants p.G2019S and p.I2020T were derived 3500 and 1300 years ago, respectively. Our findings present overviews of the prevalence and distribution of LRRK2 variants in Japanese cohorts.

Effects of L-/N-Type Calcium Channel Blockers on Angiotensin II-Renin Feedback in Hypertensive Patients.

OBJECTIVES: Cilnidipine, an L-/N-type calcium channel blocker (CCB), has unique organ-protective properties due to suppression of hyperactivity in the sympathetic nervous system and renin-angiotensin system (RAS). In this study, we hypothesized that cilnidipine might exert a renoprotective effect by suppressing the RAS. METHODS: A total of 25 hypertensive patients receiving a RAS inhibitor were randomly assigned to a cilnidipine (n = 12) or amlodipine (n = 13) group. The effects of cilnidipine on proteinuria and angiotensin II-renin feedback were assessed. RESULTS: After 6 months of treatment, both systolic and diastolic blood pressures were significantly reduced to a similar extent in both groups. The urine albumin-to-creatinine ratio was significantly lower in the cilnidipine group (p < 0.05) than in the amlodipine group. Amlodipine increased plasma angiotensin I and angiotensin II levels (p < 0.05), whereas cilnidipine did not. Interestingly, the cilnidipine group had a higher ratio of angiotensin-(1-7) (Ang-(1-7)) to angiotensin II in plasma than the amlodipine group (p < 0.05). CONCLUSIONS: The L-/N-type CCB cilnidipine, but not amlodipine, decreased urinary albumin excretion in hypertensive patients. Cilnidipine also increased the ratio of Ang-(1-7) to angiotensin II in plasma, which might be one factor underlying its beneficial effects.

[Case of transient cortical blindness due to thrombosis of the transverse sinus].

An 62-year-old man presented visual impairment and generalized seizure. Brain CT performed on the day of admission showed thrombus in the right transverse sinus, and DWI showed high intensity areas in the bilateral occipital and parietal lobes. According to bilateral occipital lobe lesions, we considered his visual impairment as cortical blindness. He was diagnosed as venous sinus thrombosis and intravenous heparin, edaravone and osmotic diuretics were administered. MR venography performed after starting of intravenous treatment showed flow gap in the left transverse sinus but no abnormalities in the right transverse sinus. On the second day of hospitalization, his cortical blindness showed improvement and thrombus in the right transverse sinus were disappeared. This indicated that his left transverse sinus originally hypoplastic, thrombus and hemostatis in the right transverse sinus (his dominant side) caused his cortical blindness and generalized seizure. There was a recanalization in the right transverse sinus after heparin therapy.

Renoprotective and antioxidant effects of cilnidipine in hypertensive patients.

Cilnidipine, an L/N-type calcium channel blocker (CCB), has been reported to have more beneficial effects on proteinuria progression in hypertensive patients than amlodipine, an L-type CCB. The N-type calcium channel blockade that inhibits renal sympathetic nerve activity might reduce glomerular hypertension by facilitating vasodilation of the efferent arterioles. However, the precise mechanism of the renoprotective effect of cilnidipine remains unknown. Because cilnidipine exerted significantly higher antioxidant activity than amlodipine in cultured human mesangial cells, we hypothesized that cilnidipine might exert a renoprotective effect by suppressing oxidative stress. A total of 35 hypertensive patients receiving a renin-angiotensin system inhibitor were randomly assigned to a cilnidipine (n=18; 10 mg per day cilnidipine titrated to 20 mg per day) or amlodipine (n=17; 5 mg per day amlodipine titrated to 10 mg per day) group; the target blood pressure (BP) was set at 130/85 mmHg. After 6 months of treatment, systolic and diastolic BPs were significantly reduced in both of the groups, without any significant difference between the groups. The urinary albumin, 8-hydroxy-2'-deoxyguanosine (OHdG) and liver-type fatty-acid-binding protein (L-FABP) to creatinine ratios significantly decreased in the cilnidipine group (P<0.05) compared with those in the amlodipine group. The reductions in urinary albumin, 8-OHdG and L-FABP were not correlated with the change in systolic BP. In conclusion, cilnidipine, but not amlodipine, ameliorated urinary albumin excretion and decreased urinary 8-OHdG and L-FABP in the hypertensive patients. Cilnidipine probably exerts a greater renoprotective effect through its antioxidative properties.

Usefulness and economic evaluation of ADSL-based live interactive teledermatology in areas with shortage of dermatologists.

BACKGROUND: To overcome the problem of maldistribution of dermatologists in rural areas, live interactive teleconsultation systems are being used in some countries. However, these systems are not in common use because few evaluations on their efficiency and economic viability were reported. METHODS: We constructed an easy-to-use asymmetric digital subscriber line (ADSL)-based live interactive teleconsultation system and conducted 150 trial sessions between two rural hospitals and Shimane University Hospital. The clinical usefulness and economic advantages of this system were evaluated using data obtained from the trials. RESULTS: The system efficiently captured images at a resolution sufficient for specialized consultations: follicular openings were visible in the images obtained from a distance of 2 m. This system is more advantageous than a conventional clinic if the following condition is fulfilled: y ≤ 6.00 x-3.86 [x, time required for one-way travel (h); y, time required for consultation (h)]. Our two lines in trial fulfilled this condition. CONCLUSIONS: Asymmetric digital subscriber line-based live interactive teleconsultation technology is beneficial in many rural hospitals that do not have a dermatologist.