Assessment of self-/parent-reported quality of life in Japanese children with haemophilia using the Japanese version of KIDSCREEN-52.

INTRODUCTION: Assessing health-related quality of life (HRQOL) is critical for providing comprehensive clinical care to patients with haemophilia. HRQOL in individuals with similar cultural backgrounds should be compared using internationally standardized, generic questionnaires. AIM: To evaluate self-/parent-assessed HRQOL in Japanese children and adolescents with haemophilia A or B. METHODS: Children and adolescents aged 8-18 years were enrolled. The haemophilia group comprised families with haemophilia, and the control group comprised those without chronic illness. HRQOL was assessed using the self-/parent-reported questionnaire KIDSCREEN-52, the Japanese version. The Oslo 3-Item Social Support Scale was investigated. RESULTS: The questionnaire was completed by 36 families in the haemophilia group and 160 parents and children in the control group. Haemophilia children aged 8-12 years had lower scores for 'moods and emotions' than control children; the parents had lower scores in the haemophilia group than in the control group for 'moods and emotions', 'social support and peers', and 'school environment'. No significant differences in HRQOL were observed between both groups of adolescents aged 13-18 years or their parents. Neck-shoulder pain was associated with a low psychological state, including 'self-perception', but other joint pains did not affect the outcomes of the HRQOL indices. Social support weaknesses were associated with low physical and psychological states, whereas unexpected hospital visits identified low values for 'self-perception', 'autonomy', and 'school environment'. CONCLUSION: Proactive mental and clinical care in haemophilia families, especially with young children, will foster a better environment for patients and their parents and ease concerns about progress in haemophilia.

Rational Molecular Design and Synthesis of Highly Thermo- and Photostable Near-Infrared-Absorbing Heptamethine Cyanine Dyes with the Use of Fluorine Atoms.

Highly thermo- and photostable, near-infrared-absorbing heptamethine cyanine dyes were achieved with the use of fluorine-containing components. In particular, one prepared heptamethine cyanine dye, bearing a tetrakis(pentafluorophenyl)borate as a counter anion and an N-ethyl-2,2,2-trifluoroacetamido group at the meso position, showed not only a high decomposition temperature (Tdt ), but also very high photostability toward white LED irradiation.

Spatiotemporal Pinpoint Cooling Sensation Produced by Ultrasound-Driven Mist Vaporization on Skin.

In this study, we achieved a noncontact tactile display that presents a pinpoint and instantaneous cooling sensation on the skin surface with no devices directly in contact with the user's body. We employed ultrasound phased arrays to generate a focused ultrasound, which locally and instantaneously expedites the vaporization of room-temperature water mist floating near the surface of the user's skin, offering a sudden pinpoint cooling sensation. In this article, we describe the physical configuration of the proposed method and show the measurement results, demonstrating how the user's skin surface was cooled. During the experiments, we discovered that a part of the skin exposed to a focused ultrasound within the floating mist was selectively cooled with negligible delay. Our prototype system offers a cooling spot of approximately 15 mm in diameter, which causes a temperature decrease of 4.6 K in 1 s and 3.3 K in the first 0.5 s on a hand situated 500 mm away from the device. Additionally, the ultrasound-driven cooling spot can be controlled on the skin surface, which is felt as a cool moving spot. Such a position-free cooling system with a high spatiotemporal resolution will open the door to unprecedented practical tactile applications.

Immuno and lectin histochemistry for renal electron microscopy.

The combination of histochemical techniques and electron microscopy is a powerful tool to study the mechanisms and pathology of renal disease. Through the use of electron-dense markers such as colloidal gold, biologists are able to localize immune deposits, cellular receptors, and extracellular proteins, amongst others. In this chapter, the protocols for making colloidal gold, conjugating colloidal gold to protein A, and post-embedding labeling with a protein A-gold complex are described. Finally, a parallel technique for histochemical labeling with lectin-gold complexes is provided.

Does skeletonization compromise the integrity of internal thoracic artery grafts?

BACKGROUND: There are few reports that demonstrate the chronologic changes in the functional integrity of the internal thoracic artery (ITA) wall after skeletonization. We investigated the impact of skeletonization on ITA wall integrity by immunohistochemical analyses in acute and chronic phases. METHODS: Nine mongrel dogs underwent bilateral ITA dissection with one skeletonized vessel and the other pedicled. The following studies were performed 1 week (acute phase, n = 3) and 12 weeks (chronic phase, n = 6) after ITA harvesting. All specimens of the ITAs were stained by antibodies against von Willebrand Factor (VWF), endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and proliferating cell nuclear antigen (PCNA). After observation with confocal laser scanning microscopy, quantitative analyses of the staining signal for VWF and eNOS expressed on endothelial cells were performed. RESULTS: There were significantly more microvessels positive for VWF in the adventitia of skeletonized ITAs than in the adventitia of pedicled ITAs but the expression of PCNA in both groups was minimal, as in normal vessels. iNOS was not detected in any specimen. The intensity of VWF and eNOS expressed by endothelial cells had no significant differences between groups at either phase. CONCLUSIONS: The functional integrity of skeletonized ITA was similar to that of pedicled ITA in both acute and chronic phases. Although skeletonization induced neovascularization in the adventitia it did not induce proliferation of smooth muscle cells in the media, which is supposed to be a feature of vascular remodeling.

Analysis of glomerular anionic charge status in children with IgA nephropathy using confocal laser scanning microscopy.

BACKGROUND: The proteinuria resulting from IgA nephropathy is secondary to altered charge-selective and/or size-selective properties of the glomerular capillary walls. However, the functional changes occurring within the glomerular capillary network which lead to proteinuria are still poorly understood. In this study, we analyzed the participation of charged components in the glomerular capillary and their role with respect to proteinuria in childhood IgA nephropathy. METHODS: We examined glomerular anionic charge in renal biopsy specimens with confocal laser scanning microscopy using FITC-conjugated poly-L-lysine as a cationic tracer. The renal specimens investigated were from 9 children with IgA nephropathy (IgAN(+)) associated with detectable proteinuria in a morning urine specimen, 8 children with IgA nephropathy (IgAN(-)) and 11 children with thin basement membrane disease (TBMD) with no detectable proteinuria. RESULTS: The labeling intensity of glomerular fixed anionic sites from IgAN(+) was significantly lower than that of IgAN(-) and TBMD. Staining the serial sections following methylation treatment revealed that the labeling intensity for fixed anionic sites in TBMD was significantly higher than that of both IgAN(+) and IgAN(-). On the other hand, saponification treatment resulted in significantly more intensive fluorescence in TBMD and IgAN(-) than in IgAN(+). Furthermore, statistical analysis demonstrated a significant correlation between 24-hour protein excretion and the intensity of fixed anionic sites in all patients with IgA nephropathy at pH 7.0 and following staining with saponification treatment. CONCLUSIONS: These findings suggest that a reduction of glomerular anionic charge might be causally associated with the development of proteinuria in childhood IgA nephropathy. Furthermore, sulfate components such as heparan sulfate proteoglycan might be involved initially followed by carboxyl components such as sialoglycoproteins in the glomeruli of patients with IgA nephropathy contributing to the occurrence of proteinuria. We suggest that this method represents a straightforward approach to dissect the participation of charged components in the pathogenesis of childhood IgA nephropathy and their relationship to the development of glomerular proteinuria.

[Membranous nephropathy following allogeneic peripheral blood stem cell transplantation in a boy with anaplastic large cell lymphoma].

We report the case of 13-year-old boy who had been diagnosed as having anaplastic large cell lymphoma (ALCL) when he was 11 years old. He suffered a relapse despite the chemotherapy regimens he had been subjected to. Since anaplastic lymphoma kinase (ALK), one of the important prognostic factors of ALCL, was not expressed in the tumor cells, allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-matched elder brother was performed. Eleven months after PBSCT, the patient developed nephrotic syndrome as a consequence of chronic graft-versus-host disease (GVHD). He was diagnosed as having membranous nephropathy (MN) based on the results of histological examinations. Soluble interleukin-2 receptor and anti-nuclear antibody closely reflected the clinical course of MN, therefore some immune mechanisms closely related to chronic GVHD seemed to contribute to the occurrence of MN after PBSCT.

[Shear stress-induced platelet aggregation in children with minimal change nephrotic syndrome].

Analysis of the hemostasis system using biochemical techniques in children with minimal change nephrotic syndrome (MCNS) has previously been restricted to in vitro assays. The recent introduction of measurement of shear stress-induced platelet aggregation (SIPA) using platelet-rich plasma (PRP) has facilitated detailed investigation of the hemostatic system in vivo. In order to further analyze the etiology of the thrombotic tendency exhibited by patients with childhood MCNS, we investigated SIPA at both low shear stress (L-SIPA) and high shear stress (H-SIPA) in 14 children with MCNS using PRP collected weekly after commencing prednisolone therapy. Seven patients were newly diagnosed cases of MCNS (ND) whereas the remainder had suffered a disease relapse (DR). Prior to prednisolone therapy L-SIPA, which was thought to be affected by fibrinogen (Fbg) levels, was significantly increased in both patient groups compared to normal controls (17.4 +/- 4.1% vs. 3.6 +/- 0.7%, ND vs control, p < 0.01: 11.7 +/- 3% vs. 2 +/- 0.7%, DR vs control, p < 0.01) with values declining at weekly intervals thereafter. Plasma Fbg levels in simultaneously collected samples followed a similar course. In contrast, H-SIPA, which was thought to be affected by von Willebrand factor (VWF), was significantly enhanced in MCNS patients after 1 week of prednisolone therapy compared to the controls (45 +/- 5.1% vs. 26.3 +/- 3.5%, ND vs normal, p < 0.05: 36.9 +/- 3.3% vs. 25.5 +/- 1.6%, DR vs. normal, p < 0.05). Plasma ristocetin cofactor and VWF antigen levels in simultaneously collected samples followed a similar course, whereas thrombin-antithrombin complex (TAT) levels remained constant. These results indicate that SIPA is enhanced in the acute stage of childhood MCNS, especially L-SIPA prior to the initiation of prednisolone therapy and H-SIPA after 1 week of prednisolone therapy, and that these phenomena may be affected by plasma Fbg and VWF levels, respectively. The enhanced SIPA may play an important thrombogenic role in the acute phase of childhood MCNS.

Ecthyma gangrenosum-like lesions in a healthy child after infection treated with antibiotics.

Ecthyma gangrenosum is a cutaneous infection associated most commonly with pseudomonal sepsis in the immunocompromised patient. We describe a previously healthy 4-year-old boy who developed ecthyma gangrenosum-like lesions secondary to antibiotic treatment for possible streptococcal infection. The skin, ears, and extremities were involved. This presentation emphasizes the importance of awareness of the rare complication of ecthyma gangrenosum-like lesions associated with non-Pseudomonas bacterial infection treated with antibiotics, even in a previously healthy child.

A case of idiopathic sclerosing mediastinitis in a 7-year-old Japanese boy.

UNLABELLED: Sclerosing mediastinitis is a very rare benign disorder characterised by the development of dense fibrous tissue within the mediastinum. Affected patients are typically young adults with infant cases being uncommon especially in areas without endemic histoplasmosis. We report a Japanese boy with markedly elevated serum inflammatory markers for more than 1 year in the absence of any clinical manifestations. 67Ga-scintigraphy demonstrated an accumulation in the mediastinal region and an open biopsy revealed a hard fibrous mass in the anteriosuperior mediastinum. Thus, a diagnosis of idiopathic sclerosing mediastinitis was made. CONCLUSION: To the best of our knowledge, this case is the youngest patient reported with this disorder. In patients with mediastinal mass lesions the diagnosis of sclerosing mediastinitis should be considered as well as infectious, autoimmune or neoplastic disease even in children.

Identification of the motilin cells in duodenal epithelium of premature infants.

BACKGROUND: The aim of the present study was to examine the presence of motilin in the duodenal epithelial cells of premature infants of < 32 weeks gestation. METHODS: Specimens from 10 deceased infants (gestational age: 26.4 +/- 2.7 weeks and birthweight: 808 +/- 303 g) were examined as subjects. All infants died of severe cardiopulmonary disorder or intraventricular hemorrhage (grade IV). The average survival period was 3.1 +/- 1.9 days. Autopsies were performed and formalin-fixed duodenums were immunostained with rabbit antiserum to motilin by the labeled streptavidin-biotin (LSAB) method. An adult duodenum obtained by pancreatoduodenectomy was also examined for the presence of motilin as a positive control specimen. An absorption test using motilin peptide was performed to prove the specificity of the binding with rabbit antiserum to motilin. RESULTS: Motilin-containing cells were detected in the adult specimen, and the binding by rabbit antiserum to motilin was completely inhibited by excess amounts of motilin peptide, indicating that this binding was specific to motilin. All 10 infants had presence of motilin antigen in the epithelial cells of their duodenums. CONCLUSION: This preliminary study indicates that the immunohistological analysis is specific to detect motilin-containing cells, and certifies the presence of motilin in duodenal epithelial cells of premature infants of < 32 weeks gestation, including one at only 22 weeks gestation.

Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome.

Early-onset sarcoidosis (EOS) and inheritable Blau syndrome (BS) share characteristic clinical features of juvenile-onset systemic granulomatosis syndrome that mainly affects skin, joints, and eyes. However, no direct evidence has been shown for the possible common origin of these 2 diseases. Recent discovery of CARD15 mutations in BS families encouraged us to investigate similar CARD15 mutations in EOS patients. Among 10 EOS cases retrospectively collected in Japan, heterozygous missense mutations were found in 9 cases; 4 showed a 1000C>T (R334W in amino acid change) that has been reported in BS, 4 showed novel 1487A>T (H496L), 1538T>C (M513T), 1813A>C (T605P), and 2010C>A (N670K), and 1 case showed double 1146C>G (D382E)/1834G>A (A612T) mutations on different alleles. All 6 of these variants of CARD15 showed increased basal nuclear factor (NF)-kappaB activity. These findings indicate that the majority of EOS and BS cases share the common genetic etiology of CARD15 mutations that cause constitutive NF-kappaB activation.

Successful resumption of trimethoprim-sulfamethoxazole after oral desensitisation in patients with chronic granulomatous disease.

Two patients with chronic granulomatous disease who had previously been intolerant to trimethoprim-sulfamethoxazole because of various adverse reactions completed a desensitisation protocol with a favourable clinical outcome.

Mechanism-based invention of high-speed living radical polymerization using organotellurium compounds and azo-initiators.

Kinetic analysis reveals the existence of two competing pathways in the organotellurium-mediated living radical polymerization (TERP) at elevated temperature. The rate-determining step, namely, the thermal dissociation process, could be bypassed by the addition of conventional radical initiators, and the polymerization proceeded at low temperature by the degenerative transfer-mediated polymerization. The polymerization conditions are applicable to a variety of vinyl monomers, and the desired polymers form in a highly controlled manner.

A 4-year-old girl with autosomal dominant polycystic kidney disease complicated by a ruptured intracranial aneurysm.

UNLABELLED: In patients with autosomal dominant polycystic kidney disease (ADPKD), intracranial aneurysms (ICAs) are extrarenal manifestations and may result in serious and potentially fatal outcome following rupture. Although ICAs are a well-known complication of ADPKD, nearly all cases of ICA occurring in the context of ADPKD are adults. Here, we report the case of a Japanese girl with ADPKD who developed a subarachnoid haemorrhage (SAH) due to a ruptured ICA at the age of 4 years. CONCLUSION: This report is intended to raise awareness that the use of noninvasive screening techniques such as three-dimensional CT angiography or magnetic resonance angiography to detect intracranial aneurysms should also be performed in paediatric patients with autosomal dominant polycystic kidney disease.

A girl with bilateral ovarian tumours: Frasier syndrome.

UNLABELLED: Frasier syndrome (FS) is characterised by male pseudohermaphroditism, slowly progressing nephropathy and frequent development of gonadoblastoma. The Wilms' tumour suppressor gene (WT1 gene) plays an important role in the development of the urogenital system and the gonads. A splice mutation in intron 9 of the WT1 gene was recently described in patients with FS. We analysed the WT1 gene of a Japanese patient with male pseudohermaphroditism, steroid resistant-nephr-opathy and gonadoblastoma by the polymerase chain reaction and direct sequencing and detected a heterozygous point mutation in intron 9. CONCLUSION: analysis of the Wilms' tumour suppressor gene in a patient with Frasier syndrome by the polymerase chain reaction and direct sequencing detected a + 5G -->A transition at a position of the second alternative splice region of exon 9, important for predicting the risk of the occurrence of Wilms' tumour.

Up-regulation of interleukin-2 mRNA in children with idiopathic nephrotic syndrome.

The current hypothesis for the pathogenesis of childhood idiopathic nephrotic syndrome (INS) favors the involvement of a T cell-mediated immune response. Various cytokines derived from T cells may play a critical role in INS. Previous studies have measured serum or urine cytokine levels and suggest an imbalance of the T cell-mediated immune response. To elucidate the true profile of T cell-derived cytokines, we determined interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-10, and tumor necrosis factor (TNF)-alpha mRNA expression in children with INS. We collected mRNA from peripheral blood mononuclear cells together with plasma and urine from nine children in the acute and remission phases of INS. Expression of IL-2, IFN-gamma, IL-4, IL-10, and TNF-alpha mRNA was determined by a quantitative real-time PCR assay. Plasma and urine cytokine concentrations were measured using a specific enzyme-linked immunosorbent assay. These data were compared between the acute and remission phase in the same patients. The IL-2 mRNA levels were significantly higher in the acute phase than in the remission phase, whilst no significant difference was found in the other cytokines investigated. There was no significant difference in the plasma and urine cytokine concentrations between the acute and remission phase. Our results indicate increased expression of IL-2 mRNA in the acute phase of INS, suggesting that IL-2, at least in part, might be involved in the pathophysiology of childhood INS.

Quantitative analysis of glomerular type IV collagen alpha3-5 chain expression in children with thin basement membrane disease.

Thin basement membrane disease (TBMD) and Alport syndrome, two forms of childhood nephritis, have generally been considered to be hereditary diseases. In Alport syndrome, several reports have demonstrated pathogenic mutations of the genes encoding type IV collagen alpha3, 4 and/or 5 chain [alpha3, 4 and/or 5(IV)]. Previous immunohistochemical studies indicated that these antigens were absent from the glomerular basement membrane (GBM) in Alport syndrome, whilst a normal labeling pattern was maintained in TBMD. In order to understand the role of the alpha3, 4 and/or 5(IV) antigens in TBMD, we used confocal laser scanning microscopy (CLSM) to examine cryosections of renal biopsies from 12 children with TBMD and 11 control children with IgA nephropathy (IgAN) without proteinuria. All tissue sections were stained with a mixture of FITC-conjugated rat monoclonal antibodies directed against human alpha3(IV), alpha4(IV) or alpha5(IV) and a Texas red-conjugated rat monoclonal antibody raised against human alpha2(IV). CLSM was performed and quantitative analysis of the ratio of the staining signal for alpha3(IV), alpha4(IV) or alpha5(IV) to alpha2(IV) [alpha3(IV), alpha4(IV) or alpha5(IV)/alpha2(IV)] along the GBM was determined. The average number of pixels for alpha3(IV), alpha4(IV) or alpha5(IV)/alpha2(IV) was 3.52 +/- 1.49, 3.54 +/- 1.25 and 1.09 +/- 0.49 in TBMD and 3.62 +/- 1.46, 3.99 +/- 1.53 and 1.77 +/- 0.47 in control subjects, respectively. Statistical analysis indicated that alpha5(IV)/alpha2(IV) ratio was significantly lower (p < 0.01) in children with TBMD compared to controls. These findings raise the possibility that TBMD might be caused by an abnormality of the alpha5(IV) antigen along the GBM.