Expert consensus on pharmacotherapy for tic disorders in Japan

Objective

We aimed to clarify the current status of pharmacotherapy for tic disorders and comorbidities in Japan. We used a systematic survey to collate the consensus of Japanese experts and compare it with the recent international evidence.

Pathological role of CD44 on NKT cells in carbon tetrachloride-mediated liver injury

Aim: CD44 has a variety of functions in immune regulation and signal transduction. Although CD44 is involved in the induction of several inflammatory diseases, it remains unknown whether CD44-targeting therapies are useful for liver diseases. Here, we examined whether CD44 blockade is effective in a chemical-induced liver injury model. Methods: We injected CD44 knock out (KO) or wild type mice with carbon tetrachloride (CCl(4)) and examined the difference of liver injury by immunological or histological analysis. Results: Although CD44KO mice exhibited suppressed liver injury at 6 h after CCl(4) injection with decreased inflammatory cell numbers and cytokine production, these mice showed severe liver injury at 24 h. We found that NKT cells played an important role in liver injury with increased infiltration of theliver after migration, which was independent of the CD44 pathway. In CD44NKT double-KO mice, liver injury was suppressed with reduced cytokine production and macrophage infiltration compared with CD44KO mice. Furthermore, MIP-2 derived from NKT cells or tumor necrosis factor alpha from macrophages contributed to exacerbation of the liver injury, since neutralization of MIP-2 provided significant protection against liver injury in CD44KO mice. Finally, we found that CD44KO mice exhibited excessive liver fibrosis compared with wild-type mice after repeated CCl(4) injections. Conclusion: We found that CD44 has unique characteristics for inflammatory liver diseases associated with NKT cell infiltration and activation. Furthermore, CD44-targeting therapies may need to be viewed with caution for liver diseases due to the actions of the liver immune system.     

Three patients with systemic lupus erythematosus complicated by cytomegalovirus colitis]

We report three female patients with systemic lupus erythematosus complicated by massive intestinal hemorrhage during the recovery from lupus nephritis (case 1, 2) or central nervous system lupus (case 3) on high dose corticosteroid therapy. Large number of cytomegalovirus (CMV) antigen-positive leukocytes and cessation of bleeding with concurrent disappearance of the viral antigens after ganciclovir therapy indicated CMV colitis in all of the three patients. No recurrence of the symptom and a favorable response to ganciclovir without reduction in steroid regimen was common to these patients.     

Beneficial effect of pramipexole for motor function and depression in Parkinson’s disease

We examined whether pramipexole (PPX) can influence depressive scale in normal and mild depressive parkinsonian patients. In an open study of PPX as an add-on to L-dopa therapy or single administration, 36 nondemented outpatients with Parkinson’s disease (PD) were entered first. All were in the stage II or III of Hoehn and Yahr scale (H&Y). PPX were started at 0.125 mg/day and daily doses were increased to 1.5 mg/day. At 3 months after PPX treatment, patients were re-evaluated. Hamilton Depression Rating Scale (HAM-D), Unified Parkinson’s Disease Rating Scale III, H&Y stage, and freezing of gait questionnaire were compared in patients before and after PPX treatment. These scores were significantly improved after PPX administration. There were no correlations between HAM-D and those motor functions. We suggest that PPX treatment has antidepressant effects in depressive PD patients and also ameliorates HAM-D score in nondepressive PD patients in addition to motor function.     

Remodeling of airway walls in fatal asthmatics decreases lymphatic distribution; beyond thickening of airway smooth muscle layers.

BACKGROUND: We previously reported the phenotypic distribution patterns of airway smooth muscles in fatal asthmatics; Type I asthmatics with smooth muscle bundle thickening only in large airways and Type II in whole airways. We hypothesized that increased smooth muscle bundles in the airway walls would disrupt airway lymphatics to impair airway clearance in these fatal asthmatics. METHODS: The autopsy lungs of seven fatal asthmatics (three Type I, four Type II asthmatics) and five controls were examined by immunohistochemistry to reveal the lymphatics distributed in the airway walls. The total area of lymphatics around each cross-sectioned airway was measured and its airway radius was calculated using an image analyzer system. Finally, the distribution areas of lymphatics in the same level of airways of bronchial trees were compared among Type I, Type II asthmatics and controls. RESULTS: The total area of airway lymphatics in each lung was found to be positively correlated with the airway radius (R). The distribution areas of lymphatics in larger airways (1.5 < R < 2.0 mm) of both types of asthmatics were significantly decreased than controls, and Type I asthmatics contained much less lymphatics than Type II asthmatics in these airways. The lymphatics around smaller airways (0.5 < R < 1.0 mm) were also reduced in both phenotypes of asthmatics without statistic difference between them. The airway lymphatics of these fatal asthmatics were observed to be interrupted by thickened muscle bundle layers, and by fibrotic tissues developed around these airways as well. CONCLUSIONS: These results indicate that distribution of lymphatics were decreased in the airway walls of fatal asthmatics which contained muscle bundles and fibro-connective tissues both of which were augmented in these airway walls to disrupt lymphatics, impair airway clearance and accelerate mucosal edema which would cause refractory status of these patients.     

Fluorine-19 fast recovery fast spin echo imaging for mapping 5-fluorouracil.

We investigated the effects of fast recovery (FR) to increase the sensitivity of fluorine-19 ((19)F) fast spin echo (FSE) in mapping 5-fluorouracil (5-FU) and its metabolites. We added an additional 90 degrees pulse (which flips back longitudinal magnetization at the end of the sequence) to the chemical shift selective (19)F FSE pulse sequence. In 5-FU solution, FR remarkably improved the signal-to-noise (S/N) ratio of (19)F 5-FU images, having higher effects with shorter repetition time and smaller echo train numbers. In animal studies, FR produced a conspicuous increase in (19)F signals in the urinary bladder. FR effects for (19)F signals in the liver were smaller than those in other organs but still substantial. Utilization of FR in (19)F FSE images promises more sensitive observation of (19)F metabolite maps of 5-FU and other (19)F-containing compounds that have relatively long relaxation times.     

Atypical Parkinsonism in distal myopathy with rimmed vacuoles

A patient with distal myopathy with rimmed vacuoles (DMRV) exhibited Parkinsonism with a severe writing tremor that responded poorly to levodopa. Molecular genetic analysis revealed that the patient had the D176V/V572L compound heterozygous mutation in the UDP‐N‐acetylglucosamine 2‐epimerase/N‐acetylmannosamine kinase (GNE) gene. Histopathological examination of a biopsied muscle specimen yielded findings compatible with those of DMRV, which is characterized by the presence of rimmed vacuoles without inflammatory cell infiltration in muscle fibers. The finding of normal cardiac meta‐iodobenzylguanide uptake makes the possibility of incidental Parkinson's disease in this patient unlikely. These observations raise the possibility that atypical Parkinsonism is a rare complication of DMRV associated with GNE mutation. © 2008 Movement Disorder Society