Yonemitsu H

Human herpesvirus‐6 encephalitis after bone marrow transplantation: magnetic resonance imaging could identify the involved sites of encephalitis

To the Editor: Human herpesvirus-6 (HHV-6) is a causative virus of exanthema subitum in early childhood (1). After primary infection, HHV-6 persists latently in salivary glands, lymph nodes and peripheral blood (2) and can be reactivated under the conditions of immunosuppression. In transplant recipients, HHV-6 can be an important pathogen causing various complications (3). However, only a few cases of HHV-6 encephalitis after bone marrow transplantation have been reported (4,s). Here, we describe a case of HHV-6 encephalitis developed after bone marrow transplantation, in which the involved sites were detected by magnetic resonance imaging (MRI). In August 1993, a 21-yr-old woman was presented to Chiba University Hospital with chronic myelogenous leukemia. She was treated with alpha-interferon but it was discontinued due to psychological symptoms after 2 months. She was then treated with hydroxyurea and was maintained in chronic phase. Two yr later she underwent bone marrow transplantation from an HLA phenoidentical unrelated donor with a mismatch in the HLA Class I1 subtype DRB1. Busulfan and cyclophosphamide were administered for the conditioning regimen, and short-methotrexate and cyclosporine for GVHD prophylaxis. Daily 200 mg/m2 of aciclovir every 8 h from d -3 to d 14 and biweekly 200 mg/kg of anti-cytomegalovirus antibody hightiter gamma-globulin were administered to prevent viral infection. On d 26, she developed disturbance of short-term memory and personality change with a refractory fever above 40°C. On d 29 she suddenly fell into a coma, and generalized tonic-clonic seizures occurred. There were no significant abnormalities in blood gas or electrolytes. Electroencephalogram revealed bursts of sharp waves on a background of slow waves indicating epilepsy. Lumbar puncture on d 29 demonstrated high intracranial pressure and cerebrospinal fluid analysis revealed 8 white cells/@ (100% lymphocytes). The protein, glucose and chloride levels were within normal range. Polymerase chain reaction (PCR) analysis of the cerebrospinal fluid (CSF) demonstrated HHV-6-DNA. DNA of herpes simplex type 1, cytomegalovirus and Epstein-Barr virus were not detected. Although cranial computed tomography (CT) on d 29 was normal, MRI on d 32 showed edema with petechial hemorrhage in the bilateral medial temporal lobes (Fig. 1). She was treated with diazepam and phenytoin for epilepsy and with gamma-globulin for viral infection. The patient then developed severe acute GVHD and died of respiratory failure with mycotic pneumonia. Neuroinvasion is a notable feature of HHV-6. Encephalitis caused by HHV-6 has been well documented in exanthema subitum and HHV-6 has been detected in the CSF of patients complicated with febrile convulsions (6). Recently, 2 encephalitis cases after bone marrow transplants have been reported (4, 5) . Drobyski et al. examined autopsy specimens of the hippocampus from a patient showing temporal symptoms, such as shortterm memory loss, and determined HHV-6 infection using immunohistochemical method (4). Mookerjee et al. demonstrated HHV-6 DNA using PCR methods from CSF of a patient complicated with encephalitis (5 ) . In both cases, radiological findings (CT and MRI) could not detect any abnormalities. In our case, CT showed no abnormal findings but MRI demonstrated edema on the medial temporal lobe, including the limbic system. Short-term memory loss suggested disease involvement in the limbic system. MRI changes in HHV6 encephalitis have been reported in nontransplanted children. Kamei et al. demonstrated T2prolongation of disease sites at an early stage, like the present case which showed atrophy later (7). MRI could have the potential diagnostic value to identify the involved sites in encephalitis patients.

Changes in serum erythropoietin and the reticulocyte count during chemotherapy for leukemias

Abstract:  We serially determined serum erythropoietin (Epo) and the reticulocyte count in patients with various types of leukemia during chemotherapy. Serum Epo increased soon after the initiation of chemotherapy and decreased after the termination of therapy irrespective of the types of leukemia or treatment regimen. However, it did not stay at low level but fluctuated. The reticulocyte count, on the other hand, showed a transient rise while serum Epo level descended. The value of serum Epo when increased was higher than the value expected from hemoglobin concentration; this finding was similar to that in aplastic anemia. These results suggest that myelosuppression is a major factor for the increase in serum Epo level during leukemia chemotherapy.

Pyridinoline collagen cross-links in patients with chronic viral hepatitis and cirrhosis

BACKGROUND/AIMS The mature form of collagen cross-linking increases the resistance of collagen to degradative enzymes, and thus renders the protein in the fibrotic lesions extremely stable and the fibrosis virtually irreversible. It is crucial to elucidate the extent of cross-linking in fibrotic and cirrhotic livers if we are to control the subsequent removal of the excessive deposited collagen, whether by natural enzymes or induced by therapy. We aimed to quantitate pyridinoline, a mature form of the cross-linking, in normal control livers, viral fibrotic livers with various degrees of fibrosis and viral cirrhotic livers. METHODS Needle liver biopsy samples from 75 patients with chronic viral hepatitis and 13 patients with viral liver cirrhosis, and six normal control livers were analyzed. Collagen and pyridinoline contents were determined by high-performance liquid chromatography. RESULTS Significantly higher levels of pyridinoline cross-links per collagen molecule were found in the viral cirrhotic livers (0.60 [0.46, 0.65] pmol/pmol of collagen; median [25%, 75%]) compared with those in normal livers (0.39 [0.24, 0.43] pmol/pmol of collagen, p = 0.03491). But no differences were found in levels between cirrhosis and chronic hepatitis with various degrees of fibrosis. These data suggest that liver collagen may be susceptible to degradation to a similar degree in viral cirrhosis and in chronic viral hepatitis. CONCLUSION The extent of the pyridinoline cross-linking of hepatic collagen does not seem to be responsible for the irreversibility of viral liver fibrosis.

Serum erythropoietin values and serum iron status during chemotherapy for leukemia

To the Editor: In a recent paper (l), a correlation between serum erythropoietin (Epo) levels and reticulocyte counts during chemotherapy was shown. We have also found that changes in serum iron level are similar to those in Epo level. We studied 10 patients with acute leukemia, one with chronic myelogenus leukemia and one with macroglobulinemia. These patients underwent various treatments with multiple chemotherapeutic agents. Serum Epo was measured with an enzyme immunoassay (2) and serum iron and unsaturated iron binding capacity (UIBC) were measured with a colorimetric method in which a chelating agent 2-nitro-S-(N-propyl-N-sulfopropylamine) phenol was

A new precipitation method with magnetic separation for high-density-lipoprotein cholesterol assay.

We describe a new precipitation method for high-density-lipoprotein cholesterol quantitation. The new method uses magnetic force instead of centrifugal force to separate high-density-lipoprotein from other lipoproteins that are fractioned with a precipitating reagent. The reagents used for the new method are the same as those for the conventional method except that magnetizable particles are included in the former. The magnetizable particles are used without any modifications. The correlation between the new and the centrifuge methods with dextran sulfate-magnesium chloride, sodium phosphotungstate-magnesium chloride and polyethylene glycol 6,000 were satisfactory (r = 0.990, 0.997 and 0.997, respectively). The new method, which can be combined with any precipitating reagents used in conventional methods, is very simple to perform and does not need any special equipment.