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Publications and source records attributed to K Korn.
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A group of 28 children was investigated after hematopoietic stem cell transplantation for evidence of hepatitis G virus (HGV) infection. HGV RNA was detected in 14 of the 28 patients (50%) and persisted in 9 of 11 patients with follow-up samples for up to 32 months. Whereas thrombopoiesis was delayed in 2 of the 14 HGV-RNA-negative patients (14.3%), 6 out of 14 (42.9%) patients in the HGV-RNA-positive group had a delayed thrombopoiesis and 2 of the latter group had to be retransplanted because of complete graft failure. These were the only cases with hepatitis C virus (HCV) coinfection. Significant liver diseases were also found only in these 2 patients with HGV and HCV coinfection. These results suggest that HGV infection may significantly influence the engraftment in patients after hematopoietic stem cell transplantation, particularly if coinfection with HCV occurs.
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The beneficial effect of blood transfusions on renal allografts disappeared at about the same time when hepatitis B vaccination was introduced in dialysis patients. To determine possible immunosuppressive effects of hepatitis B vaccination, we studied alloreactivity during the course of immunization. Fourteen healthy subjects without serological evidence of hepatitis B were routinely immunized against hepatitis B surface antigen. Plasma and mononuclear cells were isolated and frozen before immunization and after vaccination, respectively. Mean alloreactivity measured by [3H]thymidine uptake decreased from 64,772 cpm before immunization to 40,213 cpm after the third immunization. In crossover experiments, cellular modulation and plasma-dependent modulation of alloreactivity were observed. The immunosuppressive effect of plasma taken 4 weeks after the third vaccination correlated (r = 0.9) highly significantly (P < 0.005) with the anti-hepatitis B surface antigen antibody titer. Taken together, our data strongly suggest that hepatitis B vaccination is capable of reducing allogenic reactivity.
The risks of cell therapy as seen by the microbiologist and virologist, are not calculable. Numerous viruses with longterm persistence in the host cells, cannot be detected on the basis of an acute disease in the host. This applies, for example to herpesviruses, lentiviruses, retroviruses, hepatitis C virus, Borna disease virus and the so-called unconventional viruses. There are two reasons why testing of the donor animal ist not possible, the first being the great number of potential pathogens, the second being the fact that for some of these agents there are no signs of a diagnostic approach involving isolation or antibody detection. e.g. scrapie (BSE). Further, so far unknown viruses must be expected.
We evaluated 49 paired cerebrospinal fluid (CSF) and serum samples of 35 patients infected with the human immunodeficiency virus type 1 (HIV-1) for laboratory evidence of cytomegalovirus (CMV) infection. The patients were grouped according to clinical criteria as probable CMV encephalitis/polyradiculomyelitis, CMV retinitis, cerebral toxoplasmosis, progressive multifocal leukoencephalopathy, HIV-1-related cognitive/motor complex, HIV-1-associated myelopathy, and other neurological diseases. Paired CSF and serum samples were analysed for CMV deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR), quantitative intrathecal synthesis of immunoglobulin G (IgG) antibodies specific for recombinant phosphoprotein 150 (pp150) of CMV and CMV-specific serum IgM. Intrathecal synthesis of pp150-specific IgG was detected in 26% of patients (9/35), serum IgM was found in 23% of patients (8/35), and PCR of CSF was positive in 11% of patients (4/35). Detection of CMV-specific DNA in CSF preceded the intrathecal antibody synthesis in three patients for whom serial samples were available. PCR results of the CSF became negative in one patient with CMV polyradiculomyelitis after successful therapy with 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (DHPG). PCR has a higher diagnostic specificity in the acute phase of CMV infection than intrathecal antibody synthesis. The serum IgM response to CMV cannot be used to monitor a compartmentalized immune response in the central nervous system while an intrathecal immune response seems to be associated with recovery either spontaneously or as a result of treatment.
A nested PCR for the detection and rapid identification of human picornaviruses is described. Enteroviruses and rhinoviruses were amplified with the same set of four primers from the 5'-noncoding region. The nested primers allowed the detection of far less than 1 PFU in diluted virus stocks without Southern blot hybridization. In patients with neurological disorders (mainly aseptic meningitis), 43% of 37 specimens (11 of 21 cerebrospinal fluid specimens, 2 of 10 serum specimens, and 3 of 6 stool specimens) were positive by PCR. A total of 21% (10 of 47 specimens) of heart biopsy specimens from patients with dilative cardiomyopathy were PCR positive, whereas 3% (2 of 70 specimens) of control biopsy specimens from patients with coronary artery disease were PCR positive. PCR-amplified fragments from 27 of 29 clinical isolates and 14 of 28 patient samples were successfully serotyped by restriction enzyme digestion. Two specimens were further investigated by direct sequencing of PCR products, leading to the identification of a poliovirus type 3 isolate with a sequence that was highly divergent from previously published sequences.
To diagnose possible cytomegalovirus (CMV) infection in a 64-year-old man after renal transplantation, polymerase chain reaction (PCR), pp65 antigenaemia assay (pAA) and virus isolation in cell culture were routinely performed on a weekly basis. The PCR obtained virus DNA in peripheral blood lymphocytes for the first time in the fifth week. Two weeks later the patient complained of feeling unwell with abdominal pain and vomiting on eating. Two days later he developed a fever up to 38 degrees C and nocturnal sweats. Gastroscopy revealed marked antral gastritis which histologically showed typical cytomegalic "owl-eye" cells. The pAA was clearly positive and the cell culture started in the fifth week now showed a cytopathogenic effect. CMV gastritic having been diagnosed treatment consisted of 175 mg ganciclovir intravenously twice daily for 10 days. He became symptom-free after two days. The only side effects were thrombocytopenia down to 67,000/microliters and a rise in transaminase activities, changes which regressed later. To ensure early diagnosis and treatment of any CMV infection, specific virus diagnostic tests should be routinely undertaken after transplantation of organs from CMV-positive persons into CMV-negative patients.
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We report the case of a 40-year-old male HIV-negative renal transplant patient with allograft rejection and immunosuppressive therapy who presented with acute cytomegalovirus (CMV) encephalitis. CT and MRI of the brain were normal but EEG showed diffuse slowing and dysrhythmia. In cerebrospinal fluid (CSF) initially 81 cells/microliters were found and immunocytochemistry showed a decreased CD4/CD8 ratio and increased values of activated lymphocytes, natural killer cells and immunoglobulin-containing cells. CMV-specific IgM antibodies in CSF and serum, immunostaining of CMV antigen in CSF cells and virus culture from CSF and urine were negative. During the first 3 weeks of illness no intrathecal production of immunoglobulins could be detected. Early diagnosis of CMV encephalitis was made by in situ hybridization (ISH) on CSF cell preparations and the polymerase chain reaction (PCR) which was positive in CSF and blood. On day 26 diagnosis was confirmed by detection of CMV-specific intrathecal IgG production. The patient was treated with ganciclovir, anti-CMV immunoglobulins and intrathecal beta interferon. He recovered completely after 2 months. Our data demonstrate the usefulness of ISH and PCR in the early diagnosis of CMV encephalitis and perhaps may encourage the use of intrathecal beta interferon in other patients with this disease.