Efficacy of Ramelteon in Patients with Insomnia and Nocturia

Objectives: To study the efficacy of ramelteon for patients with insomnia and nocturia. Methods: Forty‐nine patients experiencing insomnia and two or more nocturnal voids were included. The degree of lower urinary tract symptoms and sleep disorders was evaluated using the International Prostate Symptom Score (IPSS), Pittsburg Sleep Quality Index (PSQI) 1 score, and frequency/volume chart (FVC). The patients were treated with ramelteon (8 mg) for four weeks and then reexamined by questionnaire and FVC to evaluate the therapeutic efficacies. Results: The mean IPSS score was 16.1 ± 6.9 at baseline and 12.4 ± 7.1 at four weeks. The subject scores for the number of nocturnal voids also decreased significantly from 3.3 ± 0.9 to 2.9 ± 1.0. In addition, PSQI scores improved significantly from 7.4 ± 2.9 to 5.4 ± 2.8. According to the FVC, the number of nocturnal voids decreased significantly from 3.1 ± 1.2 at baseline to 2.2 ± 1.1 at four weeks, and nighttime bladder capacity improved significantly from 181.4 ± 79.9 to 201.1 ± 93.7 mL. Conclusion: Ramelteon alleviated nocturia and disturbed sleep in patients with insomnia and nocturia and led to increased nighttime bladder capacity.     

Defective response to thrombopoietin and impaired expression of c-mpl mRNA of bone marrow cells in congenital amegakaryocytic thrombocytopenia

Congenital amegakaryocytic thrombocytopenia (CAMT) is an uncommon disorder in newborns and infants, characterized by isolated thrombocytopenia and megakaryocytopenia in the first year without physical anomalies. The defect of thrombopoiesis is not well understood. Recently, thrombopoietin (TPO), the ligand for the c-mpl receptor, was cloned. Accumulating evidence from in vitro and in vivo studies indicate that TPO plays a key role in the regulation of megakaryocytopoiesis. In this study we examined the effect of TPO on megakaryocyte colony formation from a patient with CAMT using a plasma-containing methylcellulose clonal culture. The in vitro results demonstrated a defective response to TPO in megakaryocyte colony formation from bone marrow mononuclear cells (MNC) of the patient, although interleukin-3 (IL-3) but not stem cell factor (SCF) induced only a small number of megakaryocyte colonies. These findings indicated that thrombocytopenia in CAMT could not be corrected by administration of TPO in vitro. Additionally, clonal cultures containing SCF, IL-3, IL-6 and erythropoietin showed decreased numbers of erythroid and myelocytic progenitors in the bone marrow of the patient. The serum TPO level measured by enzyme-linked immunosorbent assay was significantly higher than that in healthy controls. By PCR, marrow MNC from healthy children and from a patient with essential thrombocytosis expressed c-mpl mRNA, whereas no c-mpl mRNA was detected in marrow MNC from the patient with CAMT. There was no difference in the CD34 expression and c-kit mRNA between the CAMT patient and healthy children. The results of this study suggest that the pathophysiology in CAMT may be a defective response to TPO in haemopoietic cells through impaired expression of c-mpl mRNA.     

Haemophagocytic lymphohistiocytosis in association with granular lymphocyte proliferative disorders in early childhood: characteristic bone marrow morphology

Five paediatric cases of haemophagocytic lymphohistiocytosis (HLH) which showed proliferation of granular atypical lymphocytoid cells in bone marrow are reported. All cases were girls aged 8 months to 4 years who had marked hepatosplenomegaly. Marker analysis on peripheral blood mononuclear cells revealed an increase in the CD3⁺HLADR⁺ subset in three cases and the CD³⁻CD56⁺ subset in one case. An Epstein-Barr virus genome was detected in three cases, and monoclonality was confirmed in two cases. A characteristic morphology of large granular lymphocytes (LGL) was identified, with elongated bizarre features that resembled horsetail-, tadpole-, cucumber- or shooting star-type configurations on the bone marrow smear. Serum concentrations of soluble interleukin-2 receptor and interferon-gamma were elevated in all cases. All five cases required multi-agent chemotherapy which resulted in two complete remissions, two partial remissions and one no response. Refinement of treatment is required for these paediatric GLPD cases which probably comprise a specific high-risk subgroup among secondary HLH patients which had previously escaped notice.     

Interventional Catheterization in Kawasaki Disease

The experiences of catheter interventional treatment in Kawasaki disease are quite limited. In this article, we report our experiences of catheter intervention. We performed the percutaneous transluminal coronary revascularization (PTCR) in 18 cases, the percutaneous transluminal coronary angioplasty (PTCA) in 12, the stent implantation in 7, and the percutaneous transluminal coronary rotational ablation (PTCRA) in 7, which resulted in success in 55.5%, 75%, 100%, and 100%, respectively. In this article, we discuss the indications and methods for coronary artery lesions of long-term Kawasaki disease. PTCR is useful for treatment of acute myocardial infarction and for prevention of massive thrombus formation, particularly within 2 years from the onset of Kawasaki disease. PTCA is effective in many instances, particularly in patients without severe calcification of the coronary artery. However, neoaneurysm had developed in a certain number of the patients. Stent implantation is more preferable than PTCA, because it may potentially prevent neoaneurysmal formation and restenosis. Rotational ablation is effective for the stiff stenotic lesions with severe calcification, particularly for ring calcification, which frequently develops in the long-term Kawasaki disease patients. The intravascular ultrasound is very useful in evaluating the tissue characterization of the coronary artery and to select the treatment strategy, and to evaluate the catheter interventional treatment.     

Modulation of intestinal immune system by dietary fat intake: Relevance to Crohn's disease

Gut-associated lymphoid tissue is the major inductive site of the mucosal immune system, which is functionally independent of the systemic immune system. Both the amount and type of dietary fat modulate intestinal immune function. Absorption of long-chain fatty acids stimulates lymphocyte flux and lymphocyte blastogenesis in intestinal lymphatics. Long-chain fatty acid absorption also significantly enhances migration of T lymphocytes to Peyer's patches, possibly due to up-regulation of adhesion molecules, such as α4-integrin and L-selectin. Lipoproteins are involved in stimulation of lymphocyte function by both receptor-dependent and independent mechanisms. However, unsaturated fatty acids at higher concentrations have a suppressive effect on cell-mediated immunity via eicosanoid release, receptor affinity changes or interactions with intracellular signal transduction. Fat absorption also influences various other cells in the intestinal mucosa: increased cytokine release from intestinal epithelial cells follows long-chain fatty acid absorption. In Crohn's disease, elemental diets and total parenteral nutrition often induce remission, possibly by reducing antigenic load on activated immune cells in the intestine and, thus, down-regulating hyperreactive CD4 cells. Dietary oleic acid supplements caused an immunological reversal effect in the intestinal immune system of animals fed an elemental diet. An excess of long-chain fatty acids in an elemental diet, therefore, may negate its beneficial effect on gut-associated lymphoid tissues in Crohn's disease. In contrast, supplemental dietary fish oil apparently tends to prevent relapse of Crohn's disease. Because dietary fat intake is closely associated with immunological function of the intestinal mucosa, careful manipulation of dietary fat can be important in management of this disease.     

Frontal shift of posterior alpha activity is correlated with cognitive impairment in early Alzheimer's disease: A magnetoencephalography–beamformer study

Background: Induced‐oscillatory activity is considered a key factor for understanding functional processes in the brain. Magnetoencephalography (MEG) can measure oscillatory activity non‐invasively with higher spatial resolution than electroencephalography (EEG). However, MEG has rarely been used to explore functional abnormalities that may represent state markers in patients with Alzheimer's disease (AD). Methods: Thirteen patients with early AD and 14 age‐matched normal controls participated in the present study. Magnetoencephalography activity was acquired during eyes‐open and eyes‐closed states. Alpha event‐related synchronization (ERS) after eye closing was calculated and its cortical sources superimposed on each individual's magnetic resonance imaging (MRI) scan. The resulting functional image was converted into a Talairach‐transformed anatomical brain image and group comparisons were made. We also assessed correlations between cortical ERS sources showing significant between‐group differences in alpha activity and external clinical parameters, especially measures of cognitive function. Results: The averaged alpha ERS after eye closing appeared dominantly in posterior brain regions in both patients with AD and healthy controls. However, there was a significant increase in alpha ERS in frontal regions, maximal over the prefrontal cortex, in patients with AD relative to controls, indicating a frontal shift of the posterior dominant MEG alpha rhythm in AD patients. This frontal ERS source in the alpha band was negatively correlated with Mini‐Mental State Examination scores in the AD patient group. Conclusions: The findings indicate that a frontal shift of alpha ERS elicited by an eyes‐open/eyes‐closed paradigm may be an early brain electromagnetic change in patients with AD, probably representing a physiological state marker of the disease. Furthermore, the results confirm that the beamformer with group comparison analysis is a useful tool with which to explore functional processes in the brain, as indicated by oscillatory activity changes.     

White blood cell count,C-reactive protein and erythrocyte sedimentation rate in respiratory syncytial virus infection of the lower respiratory tract

Laboratory findings such as white blood cell (WBC) count, C-reactive protein (CRP) concentration and erythrocyte sedimentation rate (ESR) level in patients with bronchiolitis, bronchopneumonia and lobar pneumonia caused by respiratory syncytial virus (RSV) were studied. The diagnosis of having RSV infection of the lower respiratory tract was made on the presence of RSV antigen in nasopharyngeal specimens by means of enzyme immunoassay, on chest X-ray appearances and clinical manifestations. The WBC counts in the lobar pneumonia cases (n = 25, 12 288 ± 6296/mm³) were significantly greater than those for the bronchiolitis (n = 52, 9562 ± 2720/mm³) and bronchopneumonia (n = 43, 8369 ± 3714/mm³) cases. The concentrations of CRP in lobar pneumonia cases (n = 25, 6.5 ± 7.3 mg/dL) were significantly greater than those in the bronchiolitis (n = 52, 1.9 ± 2.0 mg/dL) and bronchopneumonia (n = 43, 2.1 ± 2.4 mg/dL) cases. The ESR levels in the lobar pneumonia cases (n = 24, 43.8 ± 29. mm/h) were also significantly higher than those in the bronchiolitis (n = 34, 20.1 ± 12.3 mm/h) and bronchopneumonia (n = 40, 24.7 ± 15.9 mm/h) cases. There were no significant differences in the WBC counts, the CRP concentrations and ESR levels between the bronchiolitis and bronchopneumonia cases. These results suggest that the RSV lobar pneumonia cases are coinfected with some bacterial organisms more heavily than in the RSV bronchiolitis and bronchopneumonia cases.