Successful coil embolisation of tortuous portosystemic venous shunts using a steerable microcatheter in a patient with polysplenia after a Fontan-type operation.

Portosystemic venous shunts occur in patients with polysplenia after the Fontan operation. In the long term, these shunts are associated with hyperammonaemia and portal-systemic encephalopathy. Since some shunts are long and tortuous, catheter interventions to close them could be challenging. Instead, a steerable microcatheter could be used for coil embolisation of tortuous portosystemic venous shunts.

Histological finding of maternal antibody-associated congenital heart block accompanied by large atrial septal defect and severe cardiac dysfunction.

Cardiac dysfunction commonly occurs in congenital heart block associated with maternal anti-SSA antibodies, especially after pacemaker implantation. We report the case of a 4-year-old girl with antibody-associated congenital heart block and a large secundum atrial septal defect who presented with significant cardiac dysfunction 4 years after pacemaker implantation. Histological findings were useful for determining the course of treatment and perioperative risk of intracardiac repair.

Intravascular ultrasonography-guided measurement and transcatheter closure of highly calcified patent ductus arteriosus in an older adult.

In older adults with patent ductus arteriosus, CT is widely used for duct visualisation because angiography images can be inadequate for evaluation. We report the case of a 73-year-old woman with a highly calcified patent ductus arteriosus whose CT images were insufficient for accurate measurement. Intravascular ultrasonography is useful for sizing of and guiding device closure of the duct.

Improvement in right ventricular function by mitral valve closure in hypoplastic left heart syndrome.

A male neonate presented with the aortic/mitral stenotic variant of hypoplastic left heart syndrome, wherein the suprasystemic left ventricular pressure and relatively large left ventricle had shifted the intraventricular septum. Despite bilateral pulmonary artery banding, the stroke volume was difficult to maintain owing to the compressed right ventricle, causing heart failure symptoms. Percutaneous balloon aortic valvuloplasty decreased the left ventricular pressure, restoring the right ventricular function. Norwood procedure with mitral valve closure after catheter intervention reduced the left ventricular size and improved the right ventricular function. This paper refers to the potential of mitral valve closure for hypoplastic left heart syndrome.

Efficacy of bubble contrast echocardiography in detecting pulmonary arteriovenous fistulas in children with univentricular heart after total cavopulmonary connection.

BACKGROUND: Development of pulmonary arteriovenous fistulas in patients with cavopulmonary anastomosis may result in a significant morbidity. Although the use of bubble contrast echocardiography with selective injection into both the branch pulmonary arteries in identifying pulmonary arteriovenous fistulas has been increasing, the actual efficacy of this diagnostic modality has not been properly evaluated. Thus, this study aimed to assess the efficacy of bubble contrast echocardiography in detecting pulmonary arteriovenous fistulas in children with total cavopulmonary connection. METHODS: A total of 140 patients were included. All patients underwent cardiac catheterisation. Bubble contrast echocardiographic studies were performed by injecting agitated saline solution into the branch pulmonary arteries. Transthoracic echocardiograms that use an apical view were conducted to assess the appearance of bubble contrast in the systemic ventricles. Then, the contrast echocardiogram results and other cardiac parameters were compared. RESULTS: No correlation was found between contrast echocardiogram grade and other cardiac parameters, such as pulmonary capillary wedge saturation and pulmonary artery resistance. Moreover, only 13 patients had negative results on both the right and left contrast echocardiograms, and 127 of the 140 patients had positive results on contrast echocardiograms even though they had normal pulmonary capillary wedge saturation. Results showed that bubble contrast echocardiography was a highly sensitive method and was likely to obtain false-positive results. CONCLUSIONS: Bubble contrast echocardiography might be highly false positive in detecting pulmonary arteriovenous fistulas in patients with cavopulmonary anastomosis. We have to consider how we make use of this method. Further standardisation of techniques is required.

Changes in cerebral oxygen saturation and blood flow during hypoxic gas ventilation therapy in HLHS and CoA/IAA complex with markedly increased pulmonary blood flow.

BACKGROUND: Hypoxic gas ventilation therapy has recently been performed to prevent post-birth increased pulmonary blood flow in cases of congenital heart diseases with increased pulmonary blood flow. However, how the oxygen supply to the tissues changes during breathing a hypoxic gas mixture, remains unknown. The changes in cerebral oxygen saturation and blood supply during hypoxic gas ventilation therapy using a nitrogen gas mixture were studied. METHODS AND RESULTS: Cerebral regional oxygen saturation (cerebral rSO(2)) was measured by near-infrared spectroscopy, and changes in middle cerebral artery (MCA) blood flow and an index of vascular resistance (RI) were assessed in 8 consecutive patients having congenital heart diseases with increased pulmonary blood flow. In all patients, urinary volume increased significantly, and the respiratory rate showed a clear decrease. Percutaneous oxygen saturation showed no significant change. The average of cerebral rSO(2) was 67.3% before hypoxic gas ventilation, but increased to 69.4%, 69.1%, and 70.7% within 1, 12, and 24 h after initiation of treatment, respectively. MCA blood flow significantly increased in the diastolic phase, and RI significantly improved from 0.80 to 0.68 within 12 h after initiation of therapy. CONCLUSIONS: These results indicate that hypoxic gas ventilation therapy does not decrease cerebral oxygen saturation, but safely improves the cerebral blood supply in cases of congenital heart diseases with increased pulmonary blood flow.

Clinical characteristics of thrombotic microangiopathy following ABO incompatible living donor liver transplantation.

Thrombotic microangiopathy (TMA) may develop after living donor liver transplantation (LDLT), but the mechanism is not fully understood. We retrospectively analyzed all patients undergoing LDLT at our center, including TMA patients, to elucidate the clinical characteristics and presentation and to determine which patients have a higher risk of occurrence of TMA. In all, 57 adult patients were reviewed after LDLT at our institution. TMA was diagnosed by sudden and severe thrombocytopenia, followed by hemolytic anemia with fractionated erythrocytes in the blood smear. Clinical features were compared between the TMA group and the non-TMA group. Of the 57 patients, 4 were diagnosed with posttransplantation TMA. ABO blood group (ABO)-incompatibility, cyclophosphamide (CPA), and recipient blood group (type O) were closely correlated with the occurrence of TMA. Thrombocytopenia appeared 1 to 5 days before hemolytic anemia. Coagulative function markers stayed at the same level after TMA, while marked elevation was shown in fibrinolytic function markers such as plasminogen activator inhibitor type 1 (PAI-1). TMA occurred at a higher prevalence in ABO-incompatible graft recipients. Additional factors associated with ABO-incompatible transplantation, such as an overdose of immunosuppressants, may affect the likelihood of TMA. Sudden and severe thrombocytopenia presented before hemolytic anemia and the serum levels of PAI-1 correlated well with the clinical course of TMA. In conclusion, early recognition of thrombocytopenia and elevation of PAI-1 is crucial to diagnose TMA especially in ABO-incompatible LDLT.

Use of recombinant activated factor VII to control bleeding in a young child with qualitative platelet disorder: a case report.

Defects of platelet adhesion, aggregation, secretion, or procoagulant activities can lead to bleeding diathesis of variable severity. We used recombinant activated factor VII (rFVIIa) in the treatment of uncontrolled epistaxis in a patient with a qualitative platelet disorder. We aimed to assess the efficacy of a single rFVIIa dose (100 microg/kg) in the control of mild and severe refractory epistaxis, and evaluate the influence of rFVIIa on markers of platelet adhesion and aggregation during a period of hematological stability (i.e. non-bleeding, no medication). The efficacy study showed mild episodes of epistaxis could be successfully managed using a single rFVIIa (100 microg/kg) dose; however, severe bleedings were not well controlled, and platelet transfusion was required to achieve hemostasis. Hematological investigations showed ADP-induced and collagen-induced platelet aggregation increases from 20 to 34% and 16 to 30%, respectively, following rFVIIa administration. There were no differences between pre-dose and post-dose concentrations of membrane glycoproteins. rFVIIa may therefore induce platelet aggregation by activating a glycoprotein-independent aggregation pathway. rFVIIa may have a role in managing mild bleeding episodes not controlled using conventional measures in patients with a qualitative platelet disorder. Further research is needed to determine the mechanism of action, efficacy, and safety of rFVIIa in this population.

Molecular characterization of histidinemia: identification of four missense mutations in the histidase gene.

Histidinemia (MIM235800) is characterized by elevated histidine in body fluids and decreased urocanic acid in blood and skin and results from histidase (histidine ammonia lyase, EC 4.3.1.3) deficiency. It is the most frequent inborn metabolic error in Japan. Although the original description included mental retardation and speech impairment, neonatal screening programs have identified the majority of histidinemic patients with normal intelligence. Molecular characteristics of histidase in histidinemia have not been determined, and cytogenetically visible deletions of 12q22-24.1 in which histidase gene resides have not been identified in histidinemic patients. In order to investigate whether individuals with this disorder have small deletions, additions, or point mutations in the histidase gene, we screened genomic DNA isolated from 50 histidinemic individuals who were discovered by the neonatal screening program. The methods employed included polymerase chain reaction (PCR) amplification of exons 1-21 of the histidase gene, followed by mutation detection enhancement gel electrophoresis and sequencing of the PCR products displaying heteroduplex bands. Four missense mutations (R322P, P259L, R206T, and R208L), two exonic polymorphisms (T141T c.423A-->T and P259P c.777A-->G), and two intronic polymorphisms (IVS6-5T-->C and IVS9+25A-->G) were identified. The frequencies of each polymorphism estimated either by dot blot allele-specific oligonucleotide hybridization, restriction enzyme digestion, or direct sequencing of the PCR products amplified from 50 unrelated normal individuals were 0.28, 0.30, 0.40, and less than 0.01, respectively. Mutation analysis of one family demonstrated that the patient inherited R322P from the mother and P259L from the father. This report describes the first mutations occurring in the coding region of the histidase structural gene in patients with histidinemia.

Different roles of p38 MAPK and ERK in STI571-induced multi-lineage differentiation of K562 cells.

STI571 is a specific tyrosine kinase inhibitor of Abl kinase. It was previously reported that STI571 induced hemoglobin synthesis in the chronic myelogenous leukemia (CML) cell line K562. However, its mechanisms remain unknown. In this study, we demonstrated that STI571 induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and dephosphorylation of extracellular signal-regulated kinase (ERK) in K562 cells. In contrast, the phosphorylation of c-Jun N-terminal kinases (JNK) in K562 cells was not altered by STI571. We also found that STI571 induced all the myeloid (CD11b, CD13), megakaryocytic (CD41a, CD42), and erythroid (glycophorin-A) markers on K562 cells. A p38 MAPK-specific inhibitor, SB203580, inhibited the STI571-induced multi-lineage differentiation of K562 cells, indicating that p38 MAPK is crucial for this differentiation. In contrast, SB203580 did not overcome the inhibitory effect for proliferation of K562 cells, indicating that p38 MAPK activation by STI571 does not affect cell numbers. Among the hematopoietic transcription factors, the expression level of c-myb mRNA was clearly downregulated after incubation with STI571 in K562 cells. STI571-induced downregulation of c-myb mRNA was prevented by the pretreatment of K562 cells by SB203580. Our data provides insights into how p38 MAPK and ERK pathways are involved in STI571-induced differentiation of K562 cells.

Structure and promoter activity of the human glia maturation factor-gamma gene: a TATA-less, GC-rich and bidirectional promoter.

Human glia maturation factor-gamma (hGMFG) was recently identified as a gene that is homologous to glia maturation factor-beta (GMFB). In this study, we determined the organization of the 9.5-kb hGMFG gene and characterized its promoter activity. The 5'-flanking region of the first exon has putative elements for binding transcription factors Sp-1, GATA-1, AML-1a, Lyf-1 and Ets-1, but there were no TATA or CAAT boxes within a 226-bp sequence upstream from the initiation codon. Primer extension analysis and 5'RACE (rapid amplification of cDNA 5' ends) identified multiple transcription initiation sites within the region -84 to -70 nucleotides from the first ATG codon in a Kozak consensus sequence. A core promoter region was determined by transfecting a series of deletion constructs with a dual luciferase reporter system into rat astrocyte-derived ACT-57 cells. We found that 226 bp of the core promoter region exhibited bidirectional promoter activity.

Monitoring of occupational exposure to cyclohexanone by diffusive sampling and urinalysis.

The present study was initiated in order to identify the best marker of occupational exposure to cyclohexanone among cyclohexanone and its metabolites in urine. To examine if diffusive samplers are applicable to personal monitoring of exposure to cyclohexanone in workroom air, the performance of carbon cloth to adsorb cyclohexanone in air was studied by experimental exposure of the cloth to cyclohexanone at 5, 10, 25 or 50 ppm (i.e. 20, 40, 100 or 200 mg m-3) for up to 8 h. Cyclohexanone in the exposed cloth was extracted with carbon disulphide followed by gas chromatographic (GC) analysis. The cloth adsorbed cyclohexanone in proportion to the concentration (up to 50 ppm) and the duration (up to 8 h), and responded quantitatively to a 15 min exposure at 100 ppm. In a field survey, end-of-shift urine samples were collected from 24 factory workers occupationally exposed to cyclohexanone (up to 9 ppm) in combination with toluene and other solvents. Urine samples were also collected from 10 subjects with no occupational exposure to solvents. The urine samples were treated with acid or an enzyme preparation for hydrolysis, and extracted with dichloromethane or ethyl acetate. The extracts were analysed by GC for cyclohexanone, cyclohexanol, and trans- and cis-isomers of 1,2- and 1,4-cyclohexanediol. Both cyclohexanol and trans-1,2-cyclohexanediol in urine correlated significantly with time-weighted average intensity of exposure to cyclohexanone. Although trans -1,4-isomer was also excreted, its quantitative relation with cyclohexanone exposure could not be established, because the solvent extraction rate was low and unstable. Excretion of cis-isomers was not confirmed. The two analytes, cyclohexanol and trans-1,2-cyclohexanediol, appeared to be equally valid as exposure markers, but the latter may be superior to the former in the sense that it is sensitive enough to separate the exposed from the non-exposed at 1 ppm or less cyclohexanone exposure.