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.

Miller Fisher syndrome with transient coma: comparison with Bickerstaff brainstem encephalitis.

We herein report a 4-year-old boy with Miller Fisher syndrome (MFS) who presented with transient coma in addition to the typical triad of internal and external ophthalmoplegia, cerebellar ataxia and areflexia after an influenza type B infection. The electroencephalogram findings revealed intermittently generalized slow wave bursts. The cerebrospinal fluid revealed high protein and a lack of any cellular response. The serum anti-GQ1b IgG antibody was elevated in the acute phase and disappeared in the convalescent phase. The transient coma with the triad of MFS in this patient indicated an extended brainstem lesion including a reticular formation, which is also the responsible lesion of Bickerstaff brainstem encephalitis (BBE), but the magnetic resonance imaging repeatedly showed no abnormal finding. Our patient suggested the involvement of central nervous system in addition to the peripheral nerve injury in MFS. He also suggested that MFS and BBE may belong to the same group of disorders as syndrome of ophthalmoplegia, ataxia and areflexia (SOAA).

Usefulness of procalcitonin serum level for the discrimination of severe sepsis from sepsis: a multicenter prospective study.

Procalcitonin serum level has been recommended as a new marker of bacterial infectious diseases. The aim of this prospective, multicenter study was to determine the clinical usefulness of procalcitonin in differentiating patients with sepsis from those with severe sepsis. Eighty-two patients were enrolled: 20 without systemic inflammatory response syndrome (SIRS), 9 with SIRS, 34 with sepsis, and 19 with severe sepsis. The patients with severe sepsis had significantly higher procalcitonin levels (median, 36.1 ng/ml) than those with sepsis (median, 0.6 ng/ml). With a procalcitonin cutoff value of 2.0 ng/ml, sensitivity for the detection of severe sepsis and specificity for the detection of sepsis were 94.7% and 78.1%, respectively. A good correlation was found between the serum procalcitonin level and the Sepsis-Related Organ Failure Assessment (SOFA) score (r = 0.680), although no correlation was found between the C-reactive protein (CRP) level and the SOFA score. In conclusion, the procalcitonin serum level may be useful not only for aiding the diagnosis of sepsis but also for discriminating between sepsis and severe sepsis.

Multicenter prospective study of procalcitonin as an indicator of sepsis.

The clinical significance of serum procalcitonin (PCT) for discriminating between bacterial infectious disease and nonbacterial infectious disease (such as systemic inflammatory response syndrome (SIRS)), was compared with the significance of endotoxin, beta-D: -glucan, interleukin (IL)-6, and C-reactive protein (CRP) in a multicenter prospective study. The concentrations of PCT in patients with systemic bacterial infection and those with localized bacterial infection were significantly higher than the concentrations in patients with nonbacterial infection or noninfectious diseases. In addition, PCT, endotoxin, IL-6, and CRP concentrations were significantly higher in patients with bacterial infectious disease than in those with nonbacterial infectious disease (P<0.001, P<0.005, P<0.001, and P<0.001, respectively). The cutoff value of PCT for the discrimination of bacterial and nonbacterial infectious diseases was determined to be 0.5 ng/ml, which was associated with a sensitivity of 64.4% and specificity of 86.0%. Areas under the receiver operating characteristic curves (POCs) were 0.84 for PCT, 0.60 for endotoxin, 0.77 for IL-6, and 0.78 for CRP in the combined group of patients with bacterial infectious disease and those with nonbacterial infectious disease, and the area under the ROC for PCT was significantly higher than that for endotoxin (P<0.001). In patients diagnosed with bacteremia based on clinical findings, the positive rate of diagnosis with PCT was 70.2%, while that of blood culture was 42.6%. PCT is thus essential for discriminating bacterial infection from SIRS, and is superior in this respect to conventional serum markers and blood culture.

Intravenous immunoglobulin therapy induces neutrophil apoptosis in Kawasaki disease.

To investigate the effect of high-dose intravenous immunoglobulin (IVIg) on neutrophil apoptosis in Kawasaki disease (KD), we studied the in vitro spontaneous and IVIg-induced apoptosis of neutrophils by analyzing a proportion of annexin V-positive cells and cells with fragmented DNA. The mean number of peripheral neutrophils in the post-IVIg phase decreased significantly (P < 0.01) compared with that in the pre-IVIg phase. The mean proportion of spontaneous apoptotic neutrophils in the post-IVIg phase was significantly higher (P < 0.01) than that in the pre-IVIg phase, and there was a significantly positive correlation (P < 0.01) with the reduction ratio of the circulating neutrophil counts from the pre-IVIg through the post-IVIg phases. IVIg induced a dose-dependent increase in the proportion of apoptotic neutrophils in the pre-IVIg phase. As a result, the present study demonstrated a novel action in which high-dose IVIg therapy decreased the number of circulating neutrophils by accelerating their apoptosis in KD.

Different outcomes of vertical transmission of hepatitis C virus in a twin pregnancy.

The risk of vertical transmission of hepatitis C virus (HCV) from mother to infant has been well documented, but the exact mode of transmission is still unclear. In a set of monochorionic diamniotic monozygous twins, only the second baby was infected with HCV from the mother who was positive for serum HCV-RNA. The babies had an uncomplicated vaginal delivery 3 min apart and they were both bottle fed from the outset. The second baby developed clinical hepatitis that persisted to 30 months follow up. The intrauterine environment should have been identical for these twins, and therefore, the maternal HCV factors, including viral load are not the sole determining factors for mother-to-infant transmission of HCV.

Increased production of serum IgA-class antibody to lipid A in Kawasaki disease.

BACKGROUND: The etiology of Kawasaki disease (KD) remains unknown. To investigate whether a conventional bacterial antigen is involved in the pathogenesis of KD, we studied the serum response to lipopolysaccharide (LPS). METHODS: We measured the serum levels of IgG-, IgM- and IgA-class antibodies (Ab) to lipid A, a toxic site of LPS, using enzyme-linked immunosorbent assay in 20 patients with KD, 11 patients with Gram-negative bacterial infection (GNBI), 27 healthy children and 12 healthy adults. RESULTS: The serum levels of anti-lipid A IgG, IgM and IgA tended to increase with advancing age in healthy children older than 6 months of age. The mean level of anti-lipid A IgM in the acute phase of GNBI and the mean levels of anti-lipid A IgM and IgA in the acute phase of KD were found to increase significantly, in comparison to the age-matched controls. Furthermore, the mean level of anti-lipid A IgA also showed a significant increase from the acute to the subacute phases of KD. Regarding the IgA-subclass response, higher titers of anti-lipid A specific Ab were seen in the IgA2 subclass than in the IgA1 subclass. CONCLUSION: These findings indicate that KD patients demonstrate an intense response to lipid A in the IgA, especially IgA2-subclass, thus suggesting that an unusual activation of the mucosal immune response to a ubiquitous antigen derived from Gram-negative bacteria may be involved in the pathogenesis of KD.

Molecular diagnosis of cerebral aspergillosis by sequence analysis with panfungal polymerase chain reaction.

The authors describe a patient with osteosarcoma in whom a brain abscess developed after autologous peripheral stem cell transplantation. Serologic markers of fungal infection were negative, but fungal DNA was detected in the cerebrospinal fluid (CSF) by panfungal polymerase chain reaction (PCR) assay using primers derived from fungal 18S ribosomal RNA (rRNA) genes. The sequence of PCR products on the panfungal assay was identical to the 18S rRNA genes of Aspergillus species. The combination of sequence analysis and panfungal PCR assay could be useful in the diagnosis of cerebral aspergillosis.

Hepatic copper concentration in children undergoing living related liver transplantation due to Wilsonian fulminant hepatic failure.

Liver transplantation is indicated for Wilson's disease (WD) patients having the fulminant form and end-stage liver failure. To evaluate whether living related liver transplantation (LRLT) can correct the copper metabolism in WD patients, we studied two children who underwent LRLT because of fulminant hepatic failure. They were 7 and 13 yrs old at the time LRLT was performed. Serum ceruloplasmin levels, serum copper levels, copper urine excretion, and hepatic copper concentrations were measured. Serum ceruloplasmin levels (16.7 +/- 1.2 mg/dL) and serum copper levels (67.0 +/- 1.4 microg/dL) were lower than the normal range after LRLT in case 1. In both patients, urinary copper excretion was reduced markedly after LRLT, but was not normalized (case 1, 191.2 +/- 182.2 microg/d; case 2, 140.0 +/- 156.7 microg/d). Hepatic copper concentrations were slightly elevated (case 1, 158.8 +/- 44.6 microg/g dry weight; case 2, 147.0 microg/g dry weight) after LRLT in both cases, but did not exceed 250 microg/g dry weight. LRLT is a curative procedure in Wilson's disease presenting fulminant hepatic failure or advanced cirrhosis. However, this study indicates that the conditions of copper metabolism in WD patients undergoing LRLT are similar to those in heterozygous genetic carriers. Because the living related donors are the parents who carry the abnormal gene, LRLT cannot completely restore the copper balance in WD patients.

Acute self-limiting hepatitis B after immunoprophylaxis failure in an infant.

The occurrence of acute hepatitis after failure of immunoprophylaxis in cases of mother-to-infant transmission of hepatitis B virus (HBV) is uncommon. Because immunoprophylaxis failure is caused by the emergence of an "a" determinant escape mutant, the infants usually become HBV carriers. To evaluate whether mutations in the S gene coding for the surface protein that contains the "a" determinant are associated with acute hepatitis after immunoprophylaxis failure, HBV DNA of an infant in with acute hepatitis developed with seroconversion to anti-HBs antibodies at 12 months of age despite administration of anti-hepatitis B immunoglobulin and hepatitis B vaccine was analyzed. The S gene from HBV DNA isolated from the serum of the infant at 12, 19, and 27 months of age was cloned and sequenced. Mutations affecting amino acid residues in the first loop within the "a" determinant (codons 124-147) were found at 12 months of age. Moreover, a novel deletion mutant, with a 1-bp deletion at nucleotide 449 of the S gene, was found at 19 and 27 months of age. This deletion resulted in a frame shift and it introduced a stop codon (TAG) at codon 176. Because the open reading frame of the S gene is completely overlapped by the polymerase gene, mutations in the S gene may affect the polymerase gene. Based on this case, this study suggests that the observed frame-shift mutation in the S gene might affect the polymerase protein and induce prompt suppression of viral replication.

Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome.

Transient myeloproliferative disorder (TMD) is a leukemoid reaction occurring occasionally in Down syndrome newborn infants. Acute megakaryocytic leukemia (AMKL) develops in approximately 20% to 30% of the cases with TMD. Recently, acquired mutations in the N-terminal activation domain of the GATA-1 gene, encoding the erythroid/megakaryocytic transcription factor GATA-1, have been reported in Down syndrome-related AMKL (DS-AMKL). To understand the multistep leukemogenesis in Down syndrome, GATA-1 mutations were investigated in patients with TMD. We show here that mutations in the GATA-1 gene were detected in 21 of 22 cases with TMD. Most of the mutations in TMD were located in the regions including exon 2 and were essentially identical to those observed in DS-AMKL. In the DS-AMKL cell line, MGS, which itself expresses only a truncated mutant of GATA-1, expression of full-length GATA-1 induced the differentiation toward the erythroid lineage. However, expression of the short form of GATA-1 did not induce erythroid differentiation. These results indicate that expression of GATA-1 with a defective N-terminal activation domain contributes to the expansion of TMD blast cells and that other genetic changes contribute to the development of AMKL in Down syndrome.