A nationwide survey of newly diagnosed childhood idiopathic thrombocytopenic purpura in Japan.

BACKGROUND: We evaluated the clinical pictures, outcome for childhood idiopathic thrombocytopenic purpura (ITP) and the trends of the choice of management for childhood ITP in Japan. METHOD: Every year, questionnaires were sent to all institutions that employ the active members of the Japanese Society of Pediatric Hematology. The questionnaires included age, sex, date of diagnosis, platelet count at diagnosis, the presence or absence of antecedent infection, hemorrhagic symptoms, initial management, and the outcome of all patients newly diagnosed with ITP. RESULTS: A total of 986 newly diagnosed as ITP patients were reported between January 2000 and December 2005. The occurrence of ITP peaked in boys less than 1 year of age, and at 1 year of age in girls. The male-to-female ratio was 1.24:1. Wet purpura was observed in more than half of the patients with platelet counts of <10,000/microL. The initial treatment varied among the patients with different platelet counts at diagnosis; most of the patients with platelet counts <20,000/microL received intravenous immunoglobulin or oral corticosteroids. Conversely, cases without any aggressive treatment increased to a larger degree in patients with > or =20,000/microL of platelet. CONCLUSIONS: These findings indicate that overall compliance to the Japanese guideline is considered to be relatively good in Japan.

[GlideScope videolaryngoscope: a clinical assessment of its performance in 200 consecutive patients].

BACKGROUND: The GlideScope videolaryngoscope is a new device for endotracheal intubation, which provides a view of the glottis without alignment of the oral pharyngeal and tracheal axes. The purpose of this study was to evaluate the performance of the GlideScope in patients. METHODS: We evaluated the performance of the GlideScope" in 200 consecutive patients requiring orotracheal intubation for surgery. RESULTS: In the 200 patients, excellent (Cormack-Lehane [C-L] view 1) or good (C-L 2) laryngeal exposure was obtained in 68% and 31% respectively and successful orotracheal intubation was achieved in all the patients. The mean +/- SD time to intubate was 51 +/- 20 seconds in trainees, 52 +/- 25 seconds in junior anesthesia residents, 48 +/- 18 seconds in senior anesthesia residents, and 50 +/- 18 seconds in staff anesthetists. CONCLUSIONS: The GlideScope was easily handled not only by experienced anesthetists but also by novice personnel. The GlideScope seems to be a novel device in routine and difficult airway management.

[Nasal endotracheal intubation using GlideScope].

We describe the performance of GlideScope in 34 consecutive patients who required nasal endotracheal intubation for surgical convenience. In the 34 patients, nasal endotracheal intubation was achieved in 52 +/- 22 (mean +/- SD) sec by unexperienced clinicians, and in 50 +/- 17 sec by anesthetists in the department. Margill forceps were not needed for any patient during nasotracheal intubation. The improved coordination afforded by an image on a video monitor seen by both the assistant providing laryngeal manipulation and the anesthetist handling the laryngoscope resulted in a significant advantage over the conventional laryngoscope technique. GlideScope seems to be a novel useful device for nasal endotracheal intubation.

Sequential analysis of cadherin expression in a 4-year-old girl with intracranial ependymoma.

INTRODUCTION: Cadherins are Ca(2+)-dependent cell-to-cell adhesion molecules that play an important role in tissue construction and morphogenesis in multicellular organisms. Cadherin involvement in tumor metastasis has recently been reported. CASE REPORT: We investigated the expression of E-cadherin and N-cadherin in paraffin-embedded sequential surgical specimens and autopsy specimens from a 4-year-old girl with recurrent ependymoma, subsequent to cerebrospinal fluid (CSF) dissemination. We observed low expression of E-cadherin in all surgical specimens and autopsy specimens. In contrast, expression of N-cadherin was high in all surgical specimens, but was decreased in autopsy specimens. CONCLUSION: Decreased expression of N-cadherin may be associated with CSF dissemination and may serve as a useful marker for CSF dissemination in patients with intracranial ependymoma.

Lymphocytic hypophysitis with central diabetes insipidus and subsequent hypopituitarism masking a suprasellar germinoma in a 13-year-old girl.

CASE REPORT: We report a case of central diabetes insipidus, hypothyroidism, and subsequent hypopituitarism due to lymphocytic hypophysitis masking a germinoma in a 13-year-old pubertal girl. Magnetic resonance revealed an enlarged pituitary gland and a mass lesion in the pituitary stalk and inferior hypothalamus. Open cranial surgery of the anterior pituitary showed active hypophysitis with lymphocytic infiltrates but without necrosis. Despite prednisolone therapy, 1 year later an enlarged, irregular cystic mass lesion had developed; in the pituitary stalk and inferior hypothalamus, a endoscopic biopsy revealed germinoma. CONCLUSION: Lymphocytic hypophysitis in children may be the first sign of a host reaction to an occult germinoma. The diagnosis of central diabetes insipidus with a thickened pituitary stalk requires long-term follow-up to establish the underlying cause.

Consensus guideline for diagnosis and treatment of childhood idiopathic thrombocytopenic purpura.

A practice guideline aimed at standardizing the treatment for childhood idiopathic thrombocytopenic purpura (ITP) is presented. This consensus guideline is based on a survey carried out via a questionnaire prepared by the ITP Committee of the Japanese Society of Pediatric Hematology and sent to society members. The survey questionnaire included questions on the diagnosis of ITP submitted for the purpose of revising the ITP diagnostic guideline prepared in 1990 by the Research Group for Intractable Hematopoietic Disorders; a revised diagnostic guideline also is presented.

Hemoglobin Hammersmith [beta 42(CD1) Phe --> Ser] causing severe hemolytic anemia in a Japanese girl.

Hemoglobin Hammersmith, a rare, unstable hemoglobin variant, was diagnosed in a 9-year-old Japanese girl. She presented with the typical manifestations of this disorder, including neonatal hyperbilirubinemia, followed by progressive hepatosplenomegaly, jaundice, and bilirubinuria. Because of severe hemolytic anemia, she received transfusions of red blood cells every 3 to 4 weeks. However, she underwent splenectomy at the age of 4 years and has continued to be in partial remission without requiring further transfusions. DNA sequence analysis of the polymerase chain reaction-amplified beta-globin gene revealed a point mutation (T --> C) in the second nucleotide of the 42nd codon of the beta-globin chain (beta 42(CD1) Phe --> Ser).

Analysis of telomerase activity and RNA expression in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid.

In this study, we show that all-trans retinoic acid (ATRA) treatment leads to a rapid decrease in telomerase activity, which was associated with the reduction in myeloblasts and occurs before the appearance of myelocytes, in a patient with acute promyelocytic leukemia (APL). Microarray analysis by ATRA treatment for 48 hr in peripheral blood mononuclear cells (in vivo) and in cultured bone marrow mononuclear cells (in vitro) from a patient with APL revealed upregulation of CD11b, CD11c, CCAAT enhancer binding protein epsilon, Rb1, Mad, and tumor necrosis factor-related genes; and downregulation of hTERT, c-Myc, WT1, bcl-2, and eukaryotic translation elongation factor 1alpha2. The results might offer the potential to define the molecular mechanism underlying ATRA-induced granulocytic differentiation in patients with APL, and provide clues to identify novel molecular therapeutic targets.

Successful treatment of Diamond-Blackfan anemia with metoclopramide.

Diamond-Blackfan anemia (DBA) is a congenital anemia characterized by a low reticulocyte count, the absence or severe reduction of hemoglobin-containing cells in the bone marrow, and normal megakaryocytic and granulocytic differentiation. Although the anemia may initially respond to corticosteroid therapy, many patients require lifelong red blood cell (RBC) transfusion, leading to infectious complications and iron overload. Metoclopramide has recently been used to treat DBA. Treatment with metoclopramide induces the release of prolactin from the pituitary and stimulates erythropoiesis. For these reasons, we used metoclopramide to treat a 20-year-old man with DBA refractory to low and high doses of corticosteroids, cyclosporin A, and tacrolimus (FK506). The hemoglobin and hematocrit slowly increased, and he has remained asymptomatic and transfusion-independent for 8 months. Metoclopramide therapy should be considered in patients with refractory DBA before treatment-related complications develop.

TNFalpha induces rapid activation and nuclear translocation of telomerase in human lymphocytes.

Maintenance of telomeres regulates chromosomal stability and cellular mitosis through a checkpoint mechanism. Continuous cell proliferation requires telomerase to maintain chromosomal stability and to counteract the cellular mitotic clock. Importantly, nuclear expression of telomerase activity is required for elongation of telomere sequences. In this study, we show that tumor necrosis factor alpha (TNFalpha) induces telomerase activity in the cytoplasm of peripheral blood lymphocytes (PBL) at 60 min, followed by translocation of activated telomerase to the nucleus at 120 min. Conversely, the phosphoinositol 3-kinase (PI3K) inhibitor wortmannin blocks TNFalpha-induced activation of telomerase, whereas the specific NF-kappaB translocation inhibitor SN-50 blocks TNFalpha-induced nuclear translocation of activated telomerase. These studies suggest that activation and nuclear translocation of telomerase are regulated by PI3K/Akt/NF-kappaB signaling pathways in PBL.

Diamond-Blackfan anemia in Japan: clinical outcomes of prednisolone therapy and hematopoietic stem cell transplantation.

The epidemiology and treatment outcomes for Diamond-Blackfan anemia (DBA) were surveyed in a cohort of 54 children (M/F = 26:28) registered in Japan from 1988 to 1998. The annual incidence was 4.02 cases per million births, the median age at diagnosis was 60 days, and 59% of the cases presented by 3 months of age. Three patients had a familial occurrence. All patients received prednisolone (PSL), and cyclosporin A (CsA) was added to the therapy in 17 patients. Forty-seven patients received transfusions, and 13 underwent hematopoietic stem cell transplantation (HSCT). The cumulative probabilities of a medication-free or a transfusion-free state prior to HSCT were 36% and 69%, respectively, at more than 5 years after diagnosis. Thirteen patients were weaned from PSL therapy without HSCT, and CsA was not associated with weaning from therapy. Transfusion and medication were stopped at 249 days and 933 days after diagnosis in 34 and 13 patients, respectively, who achieved a state of independence. No initial findings predicted the treatment dependence. More than 20% of patients experienced sustained hemosiderosis and/or adverse effects of PSL. The ages and reticulocyte counts at diagnosis of the patients who underwent HSCT were lower than in the patients who did not. HSCT led to the highest success (85%) of all previous reports, even though 5 alternative donors were included in our study. Two cord blood transplants from unrelated donors failed. These findings suggest the need for developing an integral treatment strategy including selective HSCT for refractory DBA.

A botulism case of a 12-year-old girl caused by intestinal colonization of Clostridium botulinum type Ab.

We encountered a 12-year-old girl, who had contracted food-borne botulism, and subsequently suffered from obstinate constipation for more than half a year. Even on hospital day 122, Clostridium botulinum and its toxin were detected in her stool specimens. The potency of the toxin of the blood serum sampled before treatment was 20 mouse minimum lethal dose per ml. The toxin in the blood had a molecular size equivalent to that of type A botulinum neurotoxin. On hospital day 250, the patient's serum detoxified type A neurotoxin. We confirmed that the patient had food-borne botulism caused by C. botulinum type Ab, followed by intestinal colonization-type botulism.

[Management for childhood ITP].

Idiopathic thrombocytopenic purpura(ITP) is a common bleeding disorder in childhood. Approximately 80% of the disease is acute self-limited, most has minimal bleeding and achieves spontaneous recovery of platelet count. Even for the remaining who becomes chronic defined by persistent thrombocytopenia more than 6 months from the onset, high rates of complete or partial remission are also predicted. Because of generally benign outcome in childhood ITP as well as limited efficacy of treatment which is of no more than temporary benefit, therapeutic intervention to newly diagnosed ITP or to chronic disease for the prophylaxis of major hemorrhage continues to be controversial.

[Antiphospholipid antibodies in children with idiopathic thrombocytopenic purpura].

Three antiphospholipid antibodies (aPLs), namely, antiphosphatidylinositol antibody (antiinositol antibody), antiphosphatidylserine antibody (antiserine antibody), and anticardiolipin. beta 2-glycoprotein I complex antibody (antiCL. beta 2-GPI antibody), were determined in 49 children with idiopathic thrombocytopenic purpura (ITP) consisting of 14 newly-diagnosed cases and 35 chronic cases. Determination of aPL was performed twice in the newly-diagnosed patients, once each during the acute and convalescent phases, and once in the chronic patients. The positive rates in the acute and convalescent phases of the newly-diagnosed group and in the chronic group were, respectively, 14.3%, 28.6%, and 18.8% for the antiinositol antibody, 14.3%, 14.3%, and 15.6% for the antiserine antibody, and 21.4%, 28.6%, and 25.0% for either of these 2 antibodies. Thus, antiinositol and antiserine aPLs were present at high incidences; however, all patients were negative for the antiCL. beta 2-GPI antibody. No correlation was noted between either the antiinositol or the antiserine antibody and peripheral platelet count, anti-GP IIb/IIIa antibody or PAIgG. Thus, although some aPLs are present in both acute and chronic pediatric ITP, the aPLs seems to be of an infectious disease type. No results that suggest possible involvement of aPLs in ITP pathology were obtained.