Chiaki Hirano

Prevalence of Microalbuminuria and Relationship to the Risk of Cardiovascular Disease in the Japanese Population

The prevalence of microalbuminuria and its relationship to cardiovascular disease risk factors were examined in subjects participating in an annual physical and laboratory examination program. The urinary albumin concentration and the urinary albumin/creatinine ratio were determined in morning urine specimens. A turbidimetric immunoassay was used for the measurement of urinary albumin. Of the 731 subjects, 41 (5.6%) who were weakly positive or positive on a routine dipstick test for protein were excluded from the final analysis of data. Microalbuminuria was present in 14.5% of the men, in 12.4% of the women, and in 13.2% of the entire subject population when defined as a urinary albumin concentration of 30–299 μg/ml. The prevalence of microalbuminuria was significantly higher in subjects with a high normal blood pressure (15.0%) or hypertension (26.2%) as compared with normotensive subjects (6.5%). Subjects with impaired glucose tolerance (24.3%) or hyperglycemic subjects (50.0%) had a significantly higher prevalence of microalbuminuria than normoglycemic subjects (11.3%). The prevalence of microalbuminuria was significantly higher in subjects with left ventricular hypertrophy (47.1%) as compared with those with normal electrocardiograms (11.3%). A good correlation was observed between urinary albumin concentration and albumin/creatinine ratio, and both showed a significant positive correlation with age, systolic and diastolic blood pressures, and fasting plasma glucose, total serum protein, albumin, and triglyceride levels, but not with angiotensin-converting enzyme activity. Multiple regression analysis demonstrated that both the urinary albumin concentration and the albumin/creatinine ratio show a significant positive correlation with systolic blood pressure and fasting plasma glucose. The prevalence of microalbuminuria was about 13% in this Japanese cohort, and the systolic blood pressure and the fasting plasma glucose level were demonstrated as independent risk indicators for both urinary microalbumin level and urinary microalbumin/creatinine ratio.

Aicardi syndrome accompanied by auditory disturbance and multiple brain tumors

We described a 5-month-old girl with Aicardi syndrome accompanied by auditory disturbance and multiple brain tumors. She was admitted to our hospital because she suffered from intractable flexor spasms. Physical examination revealed craniofacial asymmetry, left auricular deformity, scoliosis, and remarkable hypotonia with psychomotor retardation. Abnormal ophthalmological findings included chorioretinopathy with pale and round-shaped peripapillary lacunae, and there was modified hypsarrhythmia in her EEG. MRI revealed multiple brain tumors in the 3rd and the lateral ventricles which are considered to be choroid plexus papilloma with agenesis of the corpus callosum. ACTH therapy was administered because of the intractable seizures. After ACTH therapy, the thresholds of waves I and V were much improved. The interpeak latency of waves I-V of the left ear and the peak latency of wave I of the right ear had been lengthened. Acoustic reflex with contralateral stimulation showed no response in the left ear. These findings indicate that the auditory system is also involved in the Aicardi syndrome and that ACTH is effective for its dysfunction.

Survival rate in children with fulminant hepatitis improved by a combination of twice daily plasmapheresis and intensive conservative therapy

Six of seven children with fulminant hepatitis (FH) were treated with a combination of twice daily plasmapheresis and intensive conservative therapy including special amino acid solution, glucagon-insulin therapy, dexamethasone, and so on. The remaining child was treated with intensive conservative therapy only because his condition was not so severe, in spite of being diagnosed as having fulminant hepatitis. Although five patients with biopsy-documented bridging hepatic necrosis or confluent hepatic necrosis in the acute phase made recoveries, the remaining two with massive hepatic necrosis died (the overall survival rate was 71%). The prognostic factors were considered to be the degree and pattern of liver cell necrosis, the degree of coma, and the etiology. The combination of twice daily plasmapheresis and intensive conservative therapy was effective for these pediatric patients with fulminant hepatitis, except those with massive hepatic necrosis.

Successful treatment of neutropenic enterocolitis with recombinant granulocyte colony stimulating factor in a child with acute lymphocytic leukaemia

Acyclovir for 10 days. Despite this treatment, she was referred 3 weeks later to our intensive care unit with pyrexia, disseminated vesicular and petechial eruption, bleeding of the upper digestive tract, acute pulmonary oedema, and hepatitis. A severe thrombocytopenia was found (18 x 109/1 platelet), as well as anaemia (9.3 g/dl haemoglobin) low reticulocyte count and moderate neutropenia (3.7 • 109/1 WBC and 1.2 • 109/1 PMN). Disseminated intravascular coagulation was present and treated with an exchange transfusion. Meticillin, Netilmicin and Cefotaxim were prescribed. The patients clinical status improved gradually, whereas pancytopenia persisted. On day 6, bone marrows smears exhibited a marked hypoplasia with reduction in granulocytic and erythroid lineages, and were devoid of megakaryocytes. Serological tests were positive for varicella-zoster virus with presence of IgM antibody and negative for EBV, hepatitis B, HIV and parvovirus infections. Direct Coombs test was positive and raised IgG platelet antibodies were found on days 6 and 14. During the following month, the persistence of severe thrombocytopenia led to digestive and urinary tract bleeding requiring 4 packed erythrocyte transfusions and daily platelet transfusions. The patient was also administered a commercial immunoglobulin preparation (Bio transfusion, Les Ulis, France; 400 mg/ kg per day) from day 7 to day 11. Neutropenia resolved during the following 10 days, thrombocytopenia and anaemia during the following month. Direct Coombs test was negative on day 35. Complete recovery persisted with a 6 month follow up. Varicella-related severe pneumonia, as well as encephalitis and hepatitis have been described during steroid therapy [2]. However, haematological complications are unusual, albeit some cases of immune thrombocytopenia [1, 6] and disseminated intravascular coagulation [4] have been reported. Only two cases of varicella-associated hypoplastic anaemia have been observed in the absence of any previous steroid (or other) therapy; both patients recovered in a 6-week and 3-month period respectively [3, 5]. In our case we assume that varicella was the cause of hypoplastic anaemia since: (1) pancytopenia completely resolved after the recovery from varicella; (2) serological tests for other viral infections known to be responsible for aplastic anaemia were negative; (3) Meticillin and Cefotaxim are not likely causative agents since pancytopenia appeared before initiation of this treatment. Hypoplastic anaemia was associated with auto-immune markers directed against platelets and erythrocytes, as described in other virus-related hypoplasias; therefore immunoglobulin therapy may have had a beneficial effect. This report suggests that varicella-zoster virus infection should be added to the list of possible viral causes of aplastic anaemia.

Pentanucleotide repeat and size polymorphisms in the apolipoprotein(a) gene are associated with the lipoprotein(a) concentration in chronic hemodialysis patients.

The elevation of serum or plasma lipoprotein(a) [Lp(a)] levels is regarded as an independent risk factor for cardiovascular disease, and many previous reports demonstrated that Lp(a) levels in hemodialysis patients were significantly higher than in controls. The purpose of this study was to investigate the effect of a pentanucleotide repeat polymorphism [(TTTTA)n] in the 5′-flanking region of the apolipoprotein(a) [apo(a)] gene and of a size polymorphism of apo(a) for elevated Lp(a) concentrations observed in chronic hemodialysis patients. We studied 172 patients on chronic hemodialysis and 199 healthy adults. For analysis of the pentanucleotide repeat polymorphism, polymerase chain reaction products were loaded on polyacrylamide gel for electrophoresis. apo(a) size phenotyping was performed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. The median level of Lp(a) in the patients was 14.2 mg/dl which was significantly higher than that in controls (12.0 mg/dl; p < 0.05). In the genotype of (TTTTA)8/8, the median Lp(a) level in the patients (15.9 mg/dl) was significantly higher than that in controls (13.0 mg/dl; p < 0.05). In the genotype of (TTTTA)8/8 with large-sized apo(a) isoforms (A16–A25), the patients had significantly higher Lp(a) levels than the controls (p < 0.05). In conclusion, increased Lp(a) levels in chronic hemodialysis patients were mainly attributed to the combination of eight repeats of the pentanucleotide polymorphism and large-sized isoforms of apo(a).