Mumps encephalitis with akinesia and mutism

Measles‐rubella‐mumps vaccination is routine in many countries, but the mumps vaccine remains voluntary and is not covered by insurance in Japan. A 5‐year‐old Japanese boy who had not received the mumps vaccine was affected by mumps parotitis. Several days later, he presented with various neurological abnormalities, including akinesia, mutism, dysphagia, and uncontrolled respiratory disorder. Mumps encephalitis was diagnosed. Despite steroid pulse and immunoglobulin treatment, the disease progressed. Magnetic resonance imaging showed necrotic changes in bilateral basal ganglia, midbrain, and hypothalamus. At 1 year follow up, he was bedridden and required enteral feeding through a gastric fistula and tracheostomy. Mumps vaccination should be made routine as soon as possible in Japan, because mumps encephalitis carries the risk of severe sequelae.     

Hematological study on a case with cerebellar hemangioblastoma associated with erythrocytosis,with special reference to a erythropoiesis-stimulating activity present in the fluid of the cyst of tumor

Summary A case of cerebellar hemangioblastoma associated with slight but definite erythrocytosis is reported. Operative removal of the tumor resulted in the reversion to a normal blood picture. Erythropoietin-like activity, being non-dialyzable and relatively thermolabile, was detected in the fluid aspirated from tumor. The mother of the reported patient suffered from the same disease which was also associated with a slight degree of erythrocytosis.

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Zusammenfassung Es wird über den Fall eines cerebellaren Hämangioblastoms begleitet von einer leichten, aber doch eindeutig diagnostizierten Erythrozytose berichtet. Die operative Entfernung des Tumors führte zu einer Renormalisierung des Blutbildes. In der aus dem Tumor aspirierten Flüssigkeit wurde eine erythropoetinähnliche Wirkung entdeckt, die relativ thermolabil und nicht dialysierbar war. Die Mutter des geschilderten Patienten litt an der gleichen Krankheit, die ebenfalls von einer Erythrozytose leichten Grades begleitet war.

     

Pharmacokinetics and Safety of Voriconazole Intravenous-to-Oral Switch Regimens in Immunocompromised Japanese Pediatric Patients

The aim of this study was to investigate the pharmacokinetics, safety, and tolerability of voriconazole following intravenous-to-oral switch regimens used with immunocompromised Japanese pediatric subjects (age 2 to <15 years) at high risk for systemic fungal infection. Twenty-one patients received intravenous-to-oral switch regimens based on a recent population pharmacokinetic modeling; they were given 9 mg/kg of body weight followed by 8 mg/kg of intravenous (i.v.) voriconazole every 12 h (q12h), and 9 mg/kg (maximum, 350 mg) of oral voriconazole q12h (for patients age 2 to <12 or 12 to <15 years and <50 kg) or 6 mg/kg followed by 4 mg/kg of i.v. voriconazole q12h and 200 mg of oral voriconazole q12h (for patients age 12 to <15 years and ≥50 kg). The steady-state area under the curve over the 12-h dosing interval (AUC_0–12,ss) was calculated using the noncompartmental method and compared with the predicted exposures in Western pediatric subjects based on the abovementioned modeling. The geometric mean (coefficient of variation) AUC_0–12,ss values for the intravenous and oral regimens were 51.1 μg · h/ml (68%) and 45.8 μg · h/ml (90%), respectively; there was a high correlation between AUC_0–12,ss and trough concentration. Although the average exposures were higher in the Japanese patients than those in the Western pediatric subjects, the overall voriconazole exposures were comparable between these two groups due to large interindividual variability. The exposures in the 2 cytochrome P450 2C19 poor metabolizers were among the highest. Voriconazole was well tolerated. The most common treatment-related adverse events were photophobia and abnormal hepatic function. These recommended doses derived from the modeling appear to be appropriate for Japanese pediatric patients, showing no additional safety risks compared to those with adult patients. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01383993","term_id":"NCT01383993"}}NCT01383993.)     

Hypercholesterolemia as a part of chronic GVHD after allogeneic stem cell transplantation

A 45-year-old female with acute myelogenous leukemia (AML-M6) received an allogeneic stem cell transplantation from an HLA-identical sibling donor in June 2002. Prophylaxis against graft-versus-host disease (GVHD) consisted of cyclosporine (CsA) and short-term methotrexate. Acute GVHD did not occur and CsA was discontinued on day 145 after transplantation. However, soon thereafter she suffered from conjunctivitis, stomatitis and liver dysfunction with hypercholesterolemia and was diagnosed as having chronic GVHD. The liver dysfunction and hypercholesterolemia failed to improve despite the administration of CsA and prednisolone. Atrovastatin was not effective and immunosuppressive therapy for two months including ursodeoxycholic acid finally improved the jaundice and hypercholesterolemia. Although lipid metabolism analysis in this case disclosed the same findings as in other intrahepatic cholestatic liver diseases, the results show that the improvement of hypercholesterolemia in chronic GVHD needs the same treatment as chronic GVHD.     

Acute leukemia with the phenotype of a natural killer/T cell bipotential precursor

 An acute leukemia with an unusual immunophenotype developed in a 17-year-old girl. At the initial presentation, extramedullary involvement was not evident, but with advancing disease, massive splenomegaly and an osteolytic rib tumor developed. The disease was aggressive and refractory to intensive chemotherapeutic regimens for myeloid and lymphoid malignancies, and the patient died 3 months after the initial presentation. The leukemic cells were of irregular shape and variable size; they had deeply indented or bi-lobed nuclei and relatively fine, azurophilic granules in their cytoplasm. They were positive for acid phosphatase and β-glucuronidase in granular staining, but they were negative for myeloperoxidase. The leukemic cells had a unique immunophenotype: it was positive for T-cell antigens (CD1a, CD2, cytoplasmic CD3, CD4), myeloid antigens (CD13 and CD33), NK-cell antigen (CD56), CD19 and CD30. DNA analysis revealed no gene rearrangement in the T-cell receptor β, γ and δ, or immunoglobulin heavy chain genes. The leukemic cells of our patient are thought to have arisen from the transformation of a putative precursor cell common to both the T- and NK-cell lineage in the bone marrow. The current literature on precursor NK-cell malignancy is reviewed, and its clinicopathological feature is discussed. Received: 29 April 1998 / Accepted: 28 August 1998     

Impact of mitral valve annuloplasty combined with revascularization in patients with functional ischemic mitral regurgitation.

OBJECTIVES: The aim of this work was to determine whether mitral valve (MV) annuloplasty benefits patients with moderate/severe (3+/4+) functional ischemic mitral regurgitation (MR) who undergo coronary artery bypass grafting (CABG). BACKGROUND: Mitral regurgitation is a strong predictor of poor outcomes in patients with ischemic cardiomyopathy; whether correcting it at the time of CABG improves outcomes is less certain. METHODS: From 1991 to 2003, 390 patients with 3+/4+ ischemic MR had CABG with (n = 290) or without (n = 100) MV annuloplasty. Groups were propensity-matched using demographics, extent of coronary disease, regional wall motion, and quantitative electrocardiography. Survival, echocardiographic severity of MR, and New York Heart Association (NYHA) functional class were compared. RESULTS: One-, 5-, and 10-year survival was 88%, 75%, and 47% after CABG alone and 92%, 74%, and 39% after CABG + MV annuloplasty (p = 0.6). Mortality was increased in patients with severe lateral wall motion abnormalities (p = 0.05), ST-segment elevation in lateral leads (p < 0.004), and higher QRS voltage sum (p < 0.0001). Patients undergoing CABG alone were more likely to have 3+/4+ postoperative MR than those undergoing CABG + MV annuloplasty (48% vs. 12% at 1 year, p < 0.0001). The NYHA functional class substantially improved in both groups (p < 0.001) and remained improved; at 5 years, 23% of patients having CABG + mitral annuloplasty and 25% having CABG alone were in NYHA functional class III/IV. CONCLUSIONS: Although CABG + MV annuloplasty reduces postoperative MR and improves early symptoms compared with CABG alone, it does not improve long-term functional status or survival in patients with severe functional ischemic MR. The MV annuloplasty in this setting, without addressing fundamental ventricular pathology, is insufficient to improve long-term clinical outcomes.     

Combined primary aldosteronism and Cushing's syndrome due to a single adrenocortical adenoma complicated by Hashimoto's thyroiditis

A 43-year-old Japanese woman presented hypertension, hypokalemia and typical Cushingoid signs. Autonomous secretion of both aldosterone and cortisol was shown. Abdominal computed tomography demonstrated a single tumor in the right adrenal gland, which established the diagnosis of combined primary aldosteronism and Cushing's syndrome. The resected tumor was a golden yellow-colored adenoma (diameter 4.3 cm) which expressed P450(aldo) and P450(11beta), causing oversecretion of both hormones from this adenoma. After tumor resection, overproduction of both hormones disappeared and she developed adrenal insufficiency, suggesting the strong suppression of normal adrenal function. This case was complicated by Hashimoto's thyroiditis.