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1/113. Three cases of severe subfulminant hepatitis in heart-transplanted patients after nosocomial transmission of a mutant hepatitis b virus.

    Fulminant and severe viral hepatitis are frequently associated with mutant hepatitis b virus (HBV) strains. In this study, the genetic background of a viral strain causing severe subfulminant outcome in heart-transplanted patients was studied and compared with viral hepatitis B strains that were not linked to severe liver disease in the same setting. A total of 46 patients infected nosocomially with HBV genotype A were studied. Five different viral strains were detected, infecting 3, 9, 5, 24, and 5 patients, respectively. Only one viral strain was found to be associated with the subfulminant outcome and 3 patient deaths as a consequence of severe liver disease. The remaining 43 patients with posttransplantation HBV infection did not show this fatal outcome. Instead, symptoms of hepatitis were generally mild or clinically undiagnosed. Comparison of this virus genome with the four other strains showed an accumulation of mutations in the basic core promoter, a region that influences viral replication, but also in hepatitis B X protein (HBX) (7 mutant motifs), core (10 mutant motifs), the preS1 region (5 mutant motifs), and the HBpolymerase open reading frame (17 motifs). Some of these variations, such as those in the core region, were located on the tip of the protruding spike of the viral capsid (codons 60 to 90), also known in part as an important HLA class II-restricted epitope region. These mutations might therefore influence the immune-mediated response. The viral strain causing subfulminant hepatitis was, in addition, the only strain with a preCore stop codon mutation and, thus, hepatitis B e antigen (HBeAg) expression was never observed. The combination of these specific viral factors is thought to be responsible for the fatal outcome in these immune-suppressed heart-transplant recipients.
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2/113. Idiopathic pinealitis. Case report.

    This 63-year-old man presented with complaints of "having a feeling of falling backward" over a 3-month period. Results of his general physical examination, laboratory studies, and neurological examination were unremarkable. A magnetic resonance image revealed a 1.8 x 1.4 x 1.2-cm enhancing mass in the posterior third ventricle just above the corpora quadrigemina. The pineal gland was found to be diffusely enlarged at operation and separable from the posterior thalamus and was totally resected. The patient had an uneventful postoperative course but continues to be somewhat confused. The lesion consisted of a remarkable chronic inflammatory cell infiltrate permeating the pineal lobules and was composed of T and B lymphocytes, macrophages, eosinophils, and mast cells. Immunoperoxidase studies did not demonstrate langerhans cells, and a search for microorganisms was unrevealing. There was no evidence of neoplasia; results of immunostaining for germ cell markers and other tumor-associated antigens were negative.
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3/113. Ultrastructural changes in peripheral blood neutrophils in a patient receiving ganciclovir for CMV pneumonitis following allogenic bone marrow transplantation.

    A 13-year-old splenectomized, multitransfused beta-thalassemia major, male patient received an allogenic BMT from his HLA-compatible brother after suffering grade III regimen-related pulmonary toxicity. He developed features of CMV pneumonitis with positive pp65 CMV antigenemia involving 2.5% peripheral blood neutrophils from day 46. The patient received intravenous immunoglobulin and ganciclovir 5 mg/kg intravenously twice daily. His neutrophil count was maintained above 1 x 10(9)/l by G-CSF 5 microg/kg subcutaneously as and when required. From day 7 onwards following twice daily ganciclovir his peripheral blood smear started showing isolated cytoplasmic inclusions, 1-3 per neutrophil, 3-5 mu in diameter, involving 2-3% of the neutrophils and occasional monocytes. Transmission election microscopy of peripheral blood neutrophils showed type I and type II intranuclear inclusions. These inclusions disappeared within 48 h of stopping ganciclovir. Inclusions were not seen in three patients who were given prophylactic ganciclovir 5 mg/kg once daily for 5 days every week following allogenic BMT after the same conditioning regimen. These patients were also negative for CMV antigenemia. Development of type I and type II intranuclear inclusions in blood neutrophils in patients receiving ganciclovir therapy has not been reported previously, and the striking light microscopic changes provide simple morphological evidence of the toxic effect of this drug on blood neutrophils.
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4/113. Allogenic hair transplant in a bone marrow transplant recipient.

    BACKGROUND: Autotransplantation of hair normally provides satisfactory correction of baldness. The authors suggest that the allotransplantation of hair can aid patients who have undergone bone marrow transplantation as to correct hematologic disorders. In such patients, autotransplantation of hair may be unsatisfactory because of insufficient donor hair. OBJECTIVE: To determine whether allogeneic hair grafts from bone marrow donors can grow in the bone marrow transplant recipient. methods: The authors performed a standard hair transplant using minigrafts. The patient, who presented a large bald area, had undergone bone marrow transplant due to acute lymphoblastic leukemia. The authors transplanted the patient with hair taken from the same bone marrow donor. RESULTS: The hair had very good growth and the results, according to the authors, are comparable to those of hair autotransplantation. CONCLUSION: Chemotherapy and radiation treatments can often lead to widespread, permanent hair loss. Allotransplantation of hair usually proves unsatisfactory, because skin is strongly antigenic. Bone marrow transplant patients can undergo an allotransplant of hair from the same bone marrow donor if their own donor area is inadequate.
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5/113. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with clonal lymphoproliferative disorders after orthotopic liver transplantation: a report of three cases.

    BACKGROUND/AIMS: Post-transplant lymphoproliferative disorders (PT-LPD) are a well-known complication of organ transplantation. Their incidence after liver transplantation in adults ranges from 1.8 to 4%. Reduction of immunosuppression led to remission in a few cases. Other treatments include chemotherapy, interferon alpha therapy and/or intravenous-immunoglobulins, or antiviral drugs. However, monoclonal antibodies directed against B-cell specific antigens have rarely been used in those patients. Our aim was to study the feasibility and efficacy of Rituximab, a new, promising human chimeric antibody that recognizes the CD20 antigen, for the treatment of patients with clonal lymphoproliferative disorders after orthotopic liver transplantation. methods: Rituximab (IDEC-C2HB8; Roche laboratories, Neuilly-sur-Seine, france) was administered at a 375 mg/m2 dose on days 1, 8, 15, and 22, in an outpatient setting, in three patients with PT-LPD. The tumor was classified as polymorphic PT-LPD in two cases and PT-LPD with features of large cell lymphoma in one case. All the tumors expressed the CD20 antigen and were EBV-related, and the clonality was confirmed in all three cases. The 4 injections of the anti-CD20 monoclonal antibody were associated with reduced immunosuppression in the three patient. RESULTS: The treatment with Rituximab was well tolerated without any side effects. The two patients with polymorphic PT-LPDs underwent rapid complete remission, whereas the treatment modalities were ineffective in the patient with the large-cell non-Hodgkin-lymphoma. CONCLUSION: These results must be confirmed in a larger cohort of liver transplant recipients suffering from lymphoproliferation. However, they indicate rapid efficiency of Rituximab in association with reduced immunosuppression in these disorders.
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6/113. Mycobacterial dna in recurrent sarcoidosis in the transplanted lung--a PCR-based study on four cases.

    sarcoidosis is a systemic granulomatous inflammation, which may be caused by mycobacteria other than M. tuberculosis complex (MOTT) in one-third of cases. A few cases of recurrent sarcoidosis in the transplanted lung have been reported. However, mycobacteria have been excluded by acid-fast stains only. We investigated four cases of recurrent sarcoidosis in lung transplant patients. Using PCR for the insertion sequence 6110 of mycobacterium tuberculosis complex and a second PCR for the mycobacterial chaperonin (65-kDa antigen coding sequence), we looked for mycobacterial dna. In three cases sequence analysis was also performed. One patient was negative for mycobacterial dna in explanted, but positive for M. tuberculosis dna in transplanted lung, qualifying this case as M. tuberculosis infection in the transplant. Three patients were negative for M. tuberculosis dna, but were positive for MOTT-dna in both explanted and transplanted lungs. In these three patients sequence identity of the amplified sequences before and after transplantation was proven, which rules out mycobacteriosis. Recurrent sarcoidosis does occur, but can only be proven by the exclusion of mycobacterial dna. In cases of recurrent MOTT-dna-positive sarcoidosis the diagnosis cannot be confirmed except by proof of sequence identity. Probably MOTT-dna-positive sarcoidosis is more likely to recur in a transplanted lung.
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7/113. Refractoriness to platelet transfusion following double valve replacement in an ITP patient who had undergone splenectomy.

    Reports of patients with idiopathic thrombocytopenic purpura (ITP) undergoing cardiac surgery are rare, and almost all of the reported cases required platelet transfusion. ITP patients, especially those having a history of splenectomy or a history of heavy bleeding, may have to undergo multiple platelet transfusions. Such transfusions may induce alloimmunization against the human leukocyte antigen (HLA) and result in refractoriness to subsequent platelet transfusions. We report a case of a 63-year-old female with ITP, with a history of splenectomy and multiple platelet transfusions, who underwent aortic and mitral valve replacement. Although corticosteroid administration, high-dose immunoglobulin therapy, and repeated platelet transfusion led to a temporary increase in platelet count and successful hemostasis, refractoriness to platelet transfusion occurred postoperatively because of the presence of the anti-HLA antibody. In addition, the patient showed complications of pyothorax. Corticosteroids might have exerted an inhibitory influence on the occurrence of pyothorax.
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8/113. CD-20 expression in post-transplant lymphoproliferative disorders: treatment with rituximab.

    B-cell lymphoproliferative disorders are rare but serious complications of solid organ and bone marrow transplantation. We report that these tumors frequently express the CD-20 antigen, and immunotherapy directed at this antigen may be a well-tolerated and effective treatment.
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9/113. Fatal cytomegalovirus pneumonia after preemptive antiviral therapy in a renal transplant recipient.

    cytomegalovirus (CMV) infections occur with an incidence of up to 70% in renal transplant patients and mortality is low due to effective antiviral drugs. We report here the case of a patient who suffered from an uncommonly severe and therapy-resistant pulmonary CMV infection. During the disease course, CMV-PCR from alveolar cells and lung biopsy material was repeatedly negative despite high CMV pp65 antigenemia. CMV pneumonia was finally diagnosed from a biopsy obtained by open thoracotomy revealing positive CMV immunostaining of lung tissue. The patient died of respiratory failure though double-treatment using both ganciclovir and foscavir was administered. Post mortem, the clinically suspected resistance to both antiviral drugs, but not to cidofovir, could be proven by bioassay testing of in vitro growth responses using viral cultures. CMV pneumonia may thus not be diagnosed by standard PCR techniques in rare cases and may be resistant to the available antiviral therapy. Severe CMV pneumonia may benefit from novel antiviral drugs such as cidofovir, which is currently used in the treatment of CMV retinitis in hiv patients.
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10/113. Post cardiac injury syndrome--one more cause of false positive IgG, IgM antibodies in pleural fluid against antigen-60 of mycobacterium tuberculosis.

    Post cardiac injury syndrome (PCIS) is known to occur following myocardial infarction, cardiac surgery, blunt chest trauma, percutaneous left ventricular puncture and pace-maker implantation. The diagnosis is one of exclusion. We report a case of PCIS following cardiac surgery who showed false positive IgG, IgM antibodies to antigen A60 of mycobacterium tuberculosis in pleural fluid.
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