Four-year clinical outcomes of the OLIVUS-Ex (impact of Olmesartan on progression of coronary atherosclerosis: evaluation by intravascular ultrasound) extension trial

BackgroundThe previous OLIVUS trial reported a positive role in achieving a lower rate of coronary atheroma progression through the administration of Olmesartan, an angiotension-II receptor blocking agent (ARB), for stable angina pectoris (SAP) patients requiring percutaneous coronary intervention (PCI). However, the benefits between ARB administration on long-term clinical outcomes and serial atheroma changes by IVUS remain unclear. Thus, we examined the 4-year clinical outcomes from OLIVUS according to treatment strategy with Olmesartan.MethodsSerial volumetric IVUS examinations (baseline and 14 months) were performed in 247 patients with hypertension and SAP. When these patients underwent PCI for culprit lesions, IVUS was performed in their non-culprit vessels. Patients were randomly assigned to receive 20–40 mg of Olmesartan or control, and treated with a combination of β-blockers, calcium channel blockers, glycemic control agents and/or statins per physician's guidance. Four-year clinical outcomes and annual progression rate of atherosclerosis, assessed by serial IVUS, were compared with major adverse cardio- and cerebrovascular events (MACCE).ResultsCumulative event-free survival was significantly higher in the Olmesartan group than in the control group (p = 0.04; log-rank test). By adjusting for validated prognosticators, Olmesartan administration was identified as a good predictor of MACCE (p = 0.041). On the other hand, patients with adverse events (n = 31) had larger annual atheroma progression than the rest of the population (23.8% vs. 2.1%, p < 0.001).ConclusionsOlmesartan therapy appears to confer improved long-term clinical outcomes. Atheroma volume changes, assessed by IVUS, seem to be a reliable surrogate for future major adverse cardio- and cerebrovascular events in this study cohort.     

Guidance on the use of adalimumab for juvenile idiopathic arthritis in Japan

Adalimumab is a monoclonal antibody produced by DNA recombination technology, and is the first human monoclonal antibody against human tumor necrosis factor (TNF)-α in the world. Adalimumab binds with high affinity and specificity to soluble TNF-α and normalizes its biological action. The clinical development of adalimumab started in Europe. Adalimumab was approved for the treatment of rheumatoid arthritis (RA) in December 2002 in the United States and in September 2003 in the European Union. Since then, adalimumab has been approved for the expanded indications of psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease (CD), psoriasis (Ps), and juvenile idiopathic arthritis (JIA) in the United States and the European Union, and it is now used widely for the treatment of these diseases. In Japan, adalimumab was approved for the treatment of RA in April 2008, and its use was approved for the indications of Ps and PsA in January 2010, and for CD and AS in October 2010. In Japan, children who have been diagnosed and treated according to the "Proposal for juvenile idiopathic arthritis guidance on diagnosis and treatment for primary care pediatricians and nonpediatric rheumatologists (2007)" (published in this journal in 2007; see reference 1 in the main text), but who have responded poorly to treatment must move onto the next stage of treatment. Such treatments include biological drugs, which, however, should be used with strict adherence to the indications and exclusion criteria and should be used, for the time being, only by physicians trained in how to use them. In Japan, adalimumab was approved for the treatment of JIA in July 2011. Although this drug has brought about a revolutionary advance in the treatment of JIA, it is our task to maximize its therapeutic effects and minimize its toxic effects. The guidance presented here define the indications, exclusion criteria, usage, and evaluation criteria of adalimumab for the treatment of polyarticular JIA.     

Double-Balloon Endoscopy Depicts Diminutive Small Bowel Lesions in Gastrointestinal Lymphoma

The aim was to determine the prevalence of small bowel involvement in patients with gastrointestinal (GI) lymphoma by double-balloon endoscopy (DBE). We examined 29 patients with primary GI lymphoma by oral and anal DBEs. Clinicopathologic features related to the prevalence of diminutive small bowel involvement and the clinical outcome were retrospectively investigated. Diminutive small bowel lesions were found in 14 patients. The prevalence of the lesions was not different between patients with primary small bowel lymphoma and those with primary extra-small bowel lymphoma (50% versus 47%, P = 0.6). However, clinical stage was more advanced in patients with the lesions than in those without (P < 0.05). The lesions were more frequently found in T-cell lymphoma (100%) and follicular lymphoma (77%) than in the other types of lymphoma (15%) (P < 0.05). Diminutive small intestinal lesions occur in patients with GI lymphoma, especially in those with follicular lymphoma and T-cell lymphoma. GI lymphomas of these histologic types are candidates for scrutiny by DBE.     

Leigh syndrome with Fukuyama congenital muscular dystrophy: A case report

We report the first case of Leigh syndrome (LS) with Fukuyama congenital muscular dystrophy (FCMD). A neonate suffered from lactic acidosis and subsequently presented with poor feeding, muscle weakness, hypotonia, cardiopulmonary dysfunction, and hydrocephalus. He died at 17 months. The findings of brain magnetic resonance imaging indicated some specific features of both LS and FCMD, and FCMD gene mutation was detected. Decreased mitochondrial respiratory complex I and II activity was noted. Mitochondrial DNA sequencing showed no pathogenic mutation. A case with complex I + II deficiency has rarely been reported, suggesting a nuclear gene mutation.     

Clinical characteristics of status epilepticus in an emergency hospital: importance of nonconvulsive status epilepticus]

Although nonconvulsive status epilepticus (NCSE) is a major neurological emergency, its frequency and clinical course are not well clarified. We investigated the clinical characteristics of status epilepticus focusing on the significance of NCSE. One thousand seven hundred twenty-three patients were admitted as neurological emergency cases in our hospital between October 2003 and September 2006. Of these cases, 94 (5.5%) were diagnosed as status epilepticus of which, 24 (25.5%) were diagnosed with NCSE on admission. Moreover, 8 patients who presented with convulsive status epilepticus on admission had episodes of NCSE during hospitalization. Thus, 32 patients (34.0%) suffered from NCSE during their clinical course. We analyzed the prognostic factors of status epilepticus using the Glasgow Outcome Scale. Poor outcome was significantly correlated with NCSE (p = 0.003) and acute cerebrovascular disease (p = 0.010), independent of age, sex, history of epilepsy, and other etiologies. Our study revealed that NCSE is not a rare condition and results in a poor outcome. Careful EEG evaluation of patients with consciousness disturbance might increase the diagnostic accuracy of NCSE, and aggressive treatment of patients with NCSE should be necessary to improve the prognosis of NCSE.     

A case of neuralgic amyotrophy with antiganglioside antibody]

A 54-year-old-man experienced pain from his left shoulder to his left arm and had difficulty in lifting his arm after a febrile episode. Three weeks after the onset, he was admitted to our hospital. Neurological examination demonstrated weakness and atrophy of the left deltoid muscle. Deep tendon reflexes were normal and no pathological reflexes were elicited. CSF total protein was slightly increased. The occurrence rate of F-waves was decreased in the left upper limb. Magnetic resonance imaging (MRI) study of the cervical cord and brachial plexus with and without Gadolinium infusion showed no abnormalities. Serological study showed that IgM anticytomegalovirus antibody was positive, and that serum IgM anti-GalNAc-GD1a antibody and IgM anti-GM2 antibody were positive. Symptoms were improved after treatment with mecobalamin, 1.5mg/day. This case was considered neuralgic amyotrophy after cytomegalovirus infection. The antiganglioside antibodies may play some role in its pathogenesis.     

Centrifugal lipodystrophy of the scalp presenting with an arch-form alopecia: A 10-year follow-up observation

We describe a 10-year follow-up observation of progressive arch-form alopecia caused by centrifugal lipodystrophy (CLD) in a Japanese boy. A 2.5-year-old boy developed a slightly depressed lesion demarcated by a horseshoe-shaped erythematous border on his right neck, which then extended to the scalp. Four years later, arch-form alopecia became apparent in the right temporal region along with an erythematous border. The arch-form alopecia gradually expanded centrifugally, leaving a slight residual depression, but hair regrowth was seen within the area of alopecia. Histological examination of the erythematous border revealed non-specific inflammatory changes in the subcutaneous fat. Magnetic resonance imaging findings revealed a loss of subcutaneous fat inside the lesion. The alopecia continuously extended until he was 12 years old, but, thereafter, expansion ceased and hair regrowth gradually occurred in the arch-form alopecia. A linear non-hairy lesion 5 cm in length still remained when he was 13 years old. CLD might involve the scalp and cause linear, arch-form alopecia.     

Fractionated stereotactic radiotherapy of small intracranial malignancies

Purpose: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) in patients with small intracranial malignancies.

Methods and Materials: From July 1991 to March 1997, 80 patients with a total of 121 brain or skull-base tumors were treated with FSRT alone, and were followed for periods ranging from 3 to 62 months (median 9.8). The majority of patients received 42 Gy in 7 fractions over 2.3 weeks, but in July 1993, protocols using smaller fraction doses were introduced for patients whose radiation-field diameters were larger than 3 cm or whose tumors were close to critical normal tissues.

Results: For 64 patients with metastatic brain tumors the overall median survival was 8.3 months and 1-year actuarial survival rate was 33%. Significant prognostic factors were: the presence of extracranial tumors, pre-treatment performance status, and the lung as a primary site. Patients without extracranial tumors prior to FSRT had a median survival of 21.2 months. For seven patients with high-grade glioma, 1-year actuarial local control rate was 75%, with a median survival of 10.3 months. For patients with skull-base tumors the local control was achieved in 6 of 6 patients (100%), with a median survival of 30.7 months. No one suffered from acute complications, but three patients, two of whom had undergone FSRT as the third course of radiotherapy, developed late radiation injuries.

Conclusion: Overall high local control and low morbidity rates suggest that FSRT is an effective and safe modality, even for those with a history of prior irradiation. However, patients with risk factors should be treated with smaller fraction doses.     

Aphasia following left putaminal hemorrhage. Statistical analysis of factors affecting prognosis

Multivariate and single variable analyses were employed to investigate the recovery mode of aphasia in right-handed patients with putaminal hemorrhage on the left side. Speech disturbance was evaluated using the standard language test for aphasia (SLTA) at intervals of 1, 3 and 6 months after the ictus. Recovery was assessed in relation to age, gender, volume and location of hematoma, and treatment modalities. Extension of the hematoma into the corona radiata was the factor that dominated the prognosis of aphasia at all intervals during the follow-up period. Good recovery was documented in patients with less than 2 cm2 of the hematoma volume located in the corona radiata. Recovery was poor, however, in patients with more than 12 cm2 of the hematoma in the corona radiata. While aphasia continued to improve over 6 months after the ictus, recovery was more prominent in the first 3 months. Our study precisely demonstrated that the extension into the corona radiata independently and strongly influenced the outcome of aphasia in patients with left putaminal hemorrhage.     

Myasthenia gravis induced in mice by immunization with the recombinant extracellular domain of rat muscle-specific kinase (MuSK)

Myasthenia gravis (MG) is mostly caused by anti-acetylcholine receptor (AChR) auto-antibodies (Abs). Such Abs are undetectable in 10-15% of MG patients, but many have anti-muscle-specific kinase (MuSK) Abs. We injected recombinant rat-MuSK extracellular domain in H-2(a), H-2(b), H-2(bm12) and H-2(d) mice. Certain strains exhibited exercise-induced fatigue, tremors, weight loss, and some died after 2-3 injections. Compound muscle action potentials showed decrement with low-frequency repetitive nerve stimulation. Miniature endplate potentials decreased, suggesting lower numbers of endplates functional AChRs. Myasthenic sera inhibited agrin-induced AChR aggregation in C2C12 myotubes. Conclusion: Anti-MuSK Abs induce MG, which might also result from blocking the agrin-signaling pathway.