| This report describes two cases of pediatric small bowel transplant patients who developed diffuse adenovirus enterocolitis of their allografts. Based upon the presenting symptoms for this complication, in both patients a differential diagnosis of allograft rejection versus viral infection was clinically entertained. The clinical condition in both instances rapidly deteriorated and both patients died shortly after the development of the symptoms of fulminant septicemia. Autopsies were performed and histologic examination revealed extensive denudation of the gastrointestinal mucosa with edema and a marked acute and chronic inflammatory infiltrate involving the entire wall of the grafts. Numerous viral intranuclear and intracytoplasmic inclusions were evident and an immunohistochemical stain specific for adenovirus was strongly positive in the infected cells. In addition, while in the first case the adenovirus appeared confined to the GI tract, the second patient displayed numerous viral inclusions in the lung as well as within multiple liver abscesses. At this point, the incidence of adenovirus as a cause of gastroenteritis in small bowel transplant patients remains to be determined. We believe that the importance of recognizing this particular type of viral infection in this group of patients lies primarily in differentiating it from other viral organisms (e.g., CMV) that require a specific antiviral therapy. Moreover, an identification of this entity could help avoid a misdiagnosis of rejection which could lead to an unnecessary increase in immunosuppressive therapy and a possible exacerbation of the underlying condition. ( info) |
2/142. CD4 depletion in hiv-infected haemophilia patients is associated with rapid clearance of immune complex-coated CD4 lymphocytes. The predominant immunological finding in hiv haemophilia patients is a decrease of CD4 lymphocytes during progression of the disease. Depletion of CD4 lymphocytes is paralleled by an increase in the proportion of immune complex-coated CD4 cells. We examined the hypothesis that the formation of immune complexes on CD4 lymphocytes is followed by rapid clearance of immune complex-coated CD4 lymphocytes from the circulation. In this study, the relationship of relative to absolute numbers of immune complex-loaded CD4 blood lymphocytes and their association with viral load were studied. Two measurements of relative and absolute numbers of gp120-, IgG- and/or IgM-loaded CD4 lymphocytes were analysed in hiv and hiv- haemophilia patients, with a median interval of approx. 3 years. Immune complexes on CD4 lymphocytes were determined using double-fluorescence flow cytometry and whole blood samples. viral load was assessed using NASBA and Nuclisens kits. Whereas the proportion of immune complex-coated CD4 lymphocytes increased with progression of the disease, absolute numbers of immune complex-coated CD4 lymphocytes in the blood were consistently low. Relative increases of immune complex-coated CD4 blood lymphocytes were significantly associated with decreases of absolute numbers of circulating CD4 lymphocytes. The gp120 load on CD4 blood lymphocytes increased in parallel with the viral load in the blood. These results indicate that immune complex-coated CD4 lymphocytes are rapidly cleared from the circulation, suggesting that CD4 reactive autoantibodies and immune complexes are relevant factors in the pathogenesis of AIDS. Relative increases of immune complex-positive cells seem to be a consequence of both an increasing retroviral activity as well as a stronger loading with immune complexes of the reduced number of CD4 cells remaining during the process of CD4 depletion. The two mechanisms seem to enhance each other and contribute to the progressive CD4 decrease during the course of the disease. ( info) |
3/142. 'Naive' and 'memory' CD4 T-cells and T-cell receptor (TCR) V beta repertoire dynamics are independent of the levels of viremia following hiv seroconversion. The progression of 'naive' and 'memory' T-cells and the T-cell receptor Vbeta (TCR Vbeta) repertoire dynamics within the peripheral CD4 T-cell compartment were studied in individuals following hiv seroconversion. Profound TCR Vbeta repertoire perturbations were observed within the CD4 T-cell pool in treatment-naive patients regardless of their levels of viremia during the first 6-8 months after seroconversion. The ratio of 'naive' to 'memory' CD4 T-cells as well as the TCR Vbeta repertoire dynamics did not appear to correlate with absolute numbers of CD4 T-cells. ( info) |
4/142. Disappearance of serum HCV-rna after short-term prednisolone therapy in a patient with chronic hepatitis c associated with autoimmune hepatitis-like serological manifestations. We report a 70-year-old woman with chronic hepatitis c associated with autoimmune hepatitis (AIH)-like serological manifestations, in whom elimination of hepatitis c virus (HCV) was observed after corticosteroid treatment. The patient was infected with HCV, genotype Ib, but had several laboratory findings, such as markedly elevated serum gamma-globulin and IgG, characteristic of AIH, as well as a high titer of an anti-nuclear antibody. An ultrasound (US)-guided liver biopsy disclosed chronic active hepatitis F3. Corticosteroid worsened her liver function test results and raised amounts of HCV-rna in the serum. Withdrawal of the corticosteroid led to prompt normalization of transaminase levels and the disappearance of serum HCV-rna, determined by reverse transcription-polymerase chain reaction (RT-PCR). For 4 years, up to the time of this study, her transaminase values have been normal and HCV viremia was not detected by repeated RT-PCR. We believe this to be the first reported case in which eradication of HCV was achieved by corticosteroid therapy alone, without the introduction of interferon. ( info) |
5/142. Disseminated herpes simplex virus infection in a renal transplant patient as possible cause of repeated urinary extravasations. Disseminated herpes simplex virus type 2 (HSV-2) infections are infrequent in patients receiving organ transplants, but usually have a poor outcome. We describe the case of a renal transplant patient who developed a disseminated HSV-2 infection with repeated urinary extravasations. The diagnosis was carried out using a multiplex polymerase chain reaction nested assay and it suggested HSV-2 as a possible cause of repeated urinary fistulas. ( info) |
6/142. Fibrosing cholestatic hepatitis in renal transplant recipients with hepatitis c virus infection. Fibrosing cholestatic hepatitis (FCH) has been described as a specific manifestation of hepatitis b virus (HBV) infection in liver allograft recipients characterized by a rapid progression to liver failure. Only sporadic cases have been reported in other immunocompromised groups infected with HBV and in a few transplant recipients with hepatitis c virus (HCV) infection. We present the occurrence of FCH in 4 HCV-infected renal transplant recipients within a series of 73 renal transplant recipients with HCV infection followed up closely serologically and with consecutive liver biopsies. All 4 patients received the triple-immunosuppressive regimen (azathioprine, cyclosporine A, methylprednisolone). The interval from transplantation to the appearance of liver dysfunction was 1 to 4 months and to histological diagnosis, 3 to 11 months. The biochemical profile was analogous to a progressive cholestatic syndrome in 3 patients, whereas the fourth patient had only slightly increased alanine aminotransferase and gamma-glutamyl transferase (gammaGT) levels. Liver histological examination showed the characteristic pattern of FCH in 2 patients, whereas the other 2 patients had changes compatible with an early stage. All patients were anti-HCV negative at the time of transplantation, whereas 2 patients, 1 with incomplete and 1with complete histological FCH features, seroconverted after 3 and 31 months, respectively. The patients were HCV rna positive at the time of the first liver biopsy and showed high serum HCV rna levels (14 to 58 x 10(6) Eq/mL, branched dna). HCV genotype was 1b in 3 patients and 3a in 1 patient. After histological diagnosis, immunosuppression was drastically reduced. Two patients died of sepsis and liver failure 16 and 18 months posttransplantation, whereas the seroconverted patients showed marked improvement of their liver disease, which was histologically verified in 1 patient. In conclusion, FCH can occur in HCV-infected renal transplant recipients. It seems to develop as a complication of a recent HCV infection during the period of maximal immunosuppression and is associated with high HCV viremia levels. There are indications that drastic reduction of immunosuppression may have a beneficial effect on the outcome of the disease. ( info) |
7/142. Quantitative dna analysis of low-level hepatitis B viremia in two patients with serologically negative chronic hepatitis B. Low-level viremia due to hepatitis b virus (HBV) was demonstrated in the sera of two patients diagnosed previously as having non-B, non-C chronic hepatitis. Both patients had a "silent" HBV infection, because they were negative for both hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antibody. The TaqMan chemistry polymerase chain reaction (PCR) amplified the HBV dna, enabling quantitation of the virus in their sera. Their serum HBV dna concentrations were low: the amount of each HBV S or X gene amplified showed there were approximately 10(3) copies/ml and HBV dna was detected occasionally during clinical follow-up. Positive HBsAg staining in liver tissues was demonstrated by an immunoperoxidase technique. Vertical transmission of silent HBV from one patient to her daughter was confirmed. Direct nucleotide sequencing of the amplified HBV X region revealed several mutations, suggesting reduced viral replication. One patient had a T-to-C mutation at the extreme 5'-terminus of the direct repeat 2 region and the other exhibited a coexisting X region with a 155-nucleotide deletion. These findings suggest that HBV replication is suppressed considerably in patients with silent hepatitis B. ( info) |
8/142. 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. ( info) |
| BACKGROUND/AIMS: The dynamics of hepatitis c viremia after perturbation by plasma exchange was addressed in two infected patients with symptomatic cryoglobulinemia. This approach may offer an alternative to studying patients treated with antivirals in order to understand the dynamics of hepatitis c virion exchange among different compartments in vivo. methods: plasma exchange sessions were conducted every 24 h for 3 consecutive days; hepatitis c virus rna copy numbers were evaluated in sequential plasma samples collected before (-24, -12, -8, and 0 h) and at short intervals (at 1, 3, 6, and 12 h) after each session. RESULTS: After each plasma exchange session viremia dropped by 45.3-93.3% in patient 1, and by 60.5-72.7% in patient 2, paralleling (or, in some cases, exceeding) the amount of fluid exchanged. No mobilization of cell-free hepatitis C virus from extra-vascular sites was documented during the 2-h plasma exchange. The dynamics of hepatitis c viremia after each procedure was also evaluated. Pre-plasma exchange levels were restored within 3-6 h in both patients, and the mean doubling times of residual viremia were 4.6 h and 4.5 h for patients 1 and 2, respectively. CONCLUSIONS: The results, in agreement with recent evidence indicating that the turnover of hepatitis c virions is a highly dynamic process, extend previous evaluations by documenting that large amounts of newly-produced virions are introduced into the vascular compartment within a few hours of the drop in hepatitis c viremia caused by plasma exchange. ( info) |
10/142. Changes in HCV viremia following LDL apheresis in a HCV positive patient with familial hypercholesterolemia. It has been suggested that hepatitis c virus (HCV) can be associated with beta-lipoprotein in human serum. According to this, the LDL receptor could promote endocytosis of such a virus. In the present study, we evaluated the changes in HCV viremia in a HCV positive patient with familial hypercholesterolemia, undergoing both selective (DALI System, Fresenius) and non-selective (plasma exchange) LDL apheresis. HCV-rna levels did not decrease following selective LDL apheresis, on the contrary showed a random, odd variation pattern (from -35% to 72%). Conversely, plasma exchange steadily induced a drop in HCV viremia (-35/43%), to a lower extent than that of a totally intravascular plasmaprotein, i.e., alpha 2-macroglobulin (-53/54%). These data indicate that beta-lipoprotein may not function as a plasma carrier of HCV, at least in the present case. Moreover, a continuous, quantitatively unforeseeable circulation of HCV virions from the intravascular plasma compartment to other extravascular and intracellular sites, seems to occur during an apheresis session. ( info) |