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Biomedical subjects

I Lautenschlager

Publications and source records attributed to I Lautenschlager.

At least 19 recordsLinked to original sources
PubMed2001

Comparison of plasma polymerase chain reaction and pp65-antigenemia assay in the quantification of cytomegalovirus in liver and kidney transplant patients.

BACKGROUND: Cytomegalovirus (CMV) is a significant problem in transplantation. The antiviral treatment is based on the clinical symptoms and the rapid laboratory diagnosis. Although polymerase chain reaction (PCR) methods have already been widely used, the clinical correlation of the findings is not clear. OBJECTIVE: The objective of this study was to investigate the usefulness of a quantitative plasma PCR test and compare it with the pp65-antigenemia test in the detection of clinically significant CMV infections in liver and kidney transplant patients. STUDY DESIGN: The clinical material consisted of 253 consecutive blood samples was tested using a quantitative polymerase chain reaction test, Cobas Amplicor CMV Monitor (Roche) and pp65 antigenemia assay. Plasma was used for PCR and leucocytes were used for the antigenemia test. RESULTS: CMV was detected in 89 out of 253 blood samples by one or both methods. PCR detected 78 (range 274-165000 copies/ml) and pp65 antigenemia test 79 (range 1-1500 positive cells/50000) of the positive findings. The sensitivity and specificity of PCR test was 86 and 94%, respectively. The PCR detected all clinically significant CMV infections (>10 positive cells in pp65 test) and infections which required antiviral treatment. In addition, the correlation between the two tests was almost linear. CONCLUSIONS: The quantitative PCR appears to be a suitable alternative to diagnose and monitor CMV infections in transplant patients.

Antiviral Agents↗
PubMed2000

Human herpesvirus-6 antigenemia after liver transplantation.

BACKGROUND: Human herpesvirus (HHV)-6 has recently been reported in liver transplant patients. It infects and causes dysfunction in hepatic transplants, which provides serious differential diagnostic problems between allograft rejection and viral infection. The diagnosis of posttransplantation HHV-6 infection is usually based on serology or on polymerase chain reaction detection of viral DNA in peripheral blood specimens. However, serology does not tell the exact time of the infection, and detection of viral DNA by polymerase chain reaction may also indicate a latent infection in seropositive patients. Here we report the diagnostic use of frequent monitoring of HHV-6 antigenemia after liver transplantation. METHODS: Altogether 622 blood specimens from 51 consecutive adult liver transplant patients were analyzed. The diagnosis was based on demonstration of HHV-6-specific antigens in peripheral blood mononuclear cells using immunoperoxidase staining and monoclonal antibodies and on serology. RESULTS: During the first year (7-280 days) after transplantation, HHV-6 infection was diagnosed in 11 (22%) of 51 patients. HHV-6 early antigens, as well as HHV-6 variant B antigens, were detected in all 11 patients. HHV-6 diagnosis was confirmed by serology. The episode of HHV-6 antigenemia usually lasted for several weeks together with mild, if any, clinical signs of the infection. A significant graft dysfunction was associated with HHV-6 antigenemia in 8 of 11 patients, and viral antigens were also detected in the liver biopsy specimens of 3 of these patients. CONCLUSIONS: An active HHV-6 infection can be diagnosed from peripheral blood by detection of virus-specific antigens in mononuclear cells. HHV-6 antigenemia correlated with seroresponse.

Adult↗
PubMed2000

Infections in pediatric kidney and liver transplant patients after perioperative hospitalization.

BACKGROUND: Infectious complications are a major cause of morbidity and mortality after organ transplantation. There are several reports on infections during the first months after transplantation, but there are very few data regarding infections in long-term survivors of pediatric organ transplantation. METHODS: The incidence and type of infections were retrospectively analyzed in 56 children who underwent 59 liver or renal transplantations. Follow-up was begun when the patient was sent home after a successful operation. All of the children received triple immunosuppression. RESULTS: During a mean follow-up of 4.8 years (total, 286 patient years), 1540 episodes of infection were recorded. The median incidence was 4.8 episodes/patient year. The greatest number was seen in the smallest children, 3 to 6 months after transplantation. Viral upper respiratory tract infections were the most common problem, accounting for half of the episodes (2.7 episodes/patient year). Gastroenteritis was the second most common viral infection. Only 45 episodes of infection with herpesviruses were recorded, and seven of those were caused by cytomegalovirus. Otitis media and sinusitis were the most common bacterial infections and complicated upper respiratory infection in 23% of episodes. Thirty-nine episodes of urinary tract infections were diagnosed, thirty-one in children with renal transplants. Other bacterial infections were rare, and only three episodes of verified bacterial sepsis were diagnosed. CONCLUSION: The frequency and type of infections in children with liver and renal transplants who are on triple immunosuppression are quite similar to those in age-matched healthy children.

Adolescent↗
PubMed2000

HHV-6 reactivation is often associated with CMV infection in liver transplant patients.

Human herpesvirus 6 (HHV-6) infection has been recently reported in liver transplant patients. HHV-6 is closely related to cytomegalo-virus (CMV), and some interaction between the viruses has been suggested. In this study, the post-transplant HHV-6 antigenemia was investigated in relation to symptomatic CMV infections in adult liver transplant patients. CMV infections were diagnosed by the pp65 antigenemia test and by viral cultures. HHV-6 infections were demonstrated by the HHV-6 antigenemia test and by serology. Significant symptomatic CMV infection was diagnosed in 42 of 75 patients during the first 6 months after transplantation. All CMV infections were successfully treated with ganciclovir. Concurrent HHV-6 antigenemia was detected in 21 (50%) of 42 patients with CMV infection. All HHV-6 infections were reactivations. HHV-6 also responded to the antiviral treatment, but with less clear effect. In conclusion, HHV-6 reactivation is often associated with CMV infection in liver transplant patients. The results support the suggestion that CMV and HHV-6 may have interactions.

Adult↗
PubMed2000

Expression of the cytomegalovirus genome in kidney allografts during active and latent infection.

Cytomegalovirus (CMV) infection is suggested to be a risk factor for chronic rejection. Here we investigated whether CMV can persist in renal allografts, and in which structures the viral genome is found during an acute infection and a latent period after an active infection. CMV infection was diagnosed in 72/157 patients by CMV antigenemia tests and by viral cultures. CMV antigens were demonstrated in 38 available biopsies by immunohistochemistry, and CMV genome by DNA hybridization in situ. Standard histology was also performed. CMV antigens were detected in 7/15 biopsies obtained during acute infection, in three with acute rejection, and chronic changes in the other biopsies. CMV genome was located in inflammatory cells, in tubuli and in the capillary endothelium. During a latent period without a positive finding in blood or urine, CMV antigens were still found in 6/31 biopsies. CMV DNA was found in inflammatory cells, tubular and glomerular structures and in the endothelium of the arterioles. During the latent period with persistent CMV in the graft, in most cases (10/12) mild to moderate chronic changes were recorded.

Antigens, Viral↗
PubMed2000

Sequential analysis of adhesion molecules and their ligands in rat renal allografts during the development of chronic rejection.

Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are important in endothelial cell-leukocyte interactions. In this sequential study, the expression of ICAM-1 and VCAM-1 and their ligands LFA-1 and VLA-4 as well as major histocompatibility complex class II antigens (MHC class II), and interleukin-2-receptor (IL-2R) were investigated during the development of chronic renal allograft rejection in a rat model. The time-related expression of adhesion molecules and their ligands in the graft was correlated to the chronic allograft damage index (CADI). In association with an initial short immune activation, there was a significant ICAM-1 and VCAM-1 induction in the vascular endothelium and the tubular epithelium. In the interstitium, there was infiltration of lymphocytes expressing ligand molecules VLA-4 and LFA-1, as well as activation markers MHC class II and IL-2R. Thereafter, the expression declined together with the increase of CADI-values. In end-stage chronic rejection, there was practically no expression of ICAM-1 and VCAM-1. In the interstitium, there were only few ligand-expressing leukocytes. In conclusion, adhesion molecules and their ligands are involved in the induction phase of the process but no longer in the later stages of chronic rejection.

Animals↗
PubMed2000

Induction of vascular adhesion protein-1 during liver allograft rejection and concomitant cytomegalovirus infection in rats.

Vascular adhesion protein-1 (VAP-1) is an adhesion molecule controlling lymphocyte recirculation through high endothelial venules of the lymph nodes. It has also been shown to be induced and to mediate lymphocyte adhesion at sites of inflammation. We studied the expression of VAP-1 and two other inducible adhesion molecules ICAM-1 and VCAM-1 in our experimental model of rat liver allograft rejection and, in addition, the effect of concomitant rat cytomegalovirus (RCMV) infection on this expression. Expression of VAP-1, ICAM-1, and VCAM-1 was studied in rat liver allografts with or without RCMV infection, isografts, and normal rat liver. Immunoperoxidase technique and monoclonal antibodies including a novel anti-VAP-1 reagent were used. VAP-1 expression was induced by acute rejection in sinusoids, hepatocytes, and also in bile ducts, when compared to the isografts or normal liver, where only blood vessels were consistently positive. Sinusoidal and hepatocyte expression of VAP-1 was prolonged by the presence of RCMV. ICAM-1 and VCAM-1 expression was also induced by acute rejection. However, RCMV increased sinusoidal VCAM-1 expression compared to uninfected grafts. The present experimental study shows that VAP-1 is up-regulated in acute rejection of liver allografts, and that this up-regulation is prolonged by RCMV infection.

Acute Disease↗
PubMed2000

Diagnostic implications of human cytomegalovirus immediate early-1 and pp67 mRNA detection in whole-blood samples from liver transplant patients using nucleic acid sequence-based amplification.

Nucleic acid sequence-based amplification (NASBA) was used for detection of the human cytomegalovirus (CMV) immediate early-1 (IE) and the late pp67 mRNA in 353 blood samples collected from 34 liver transplant patients. The diagnostic value of these assays was compared to that of the pp65 antigenemia assay. Overall, 95 and 42% of the antigenemia-positive samples were IE NASBA and pp67 NASBA positive, respectively. Although the results from pp67 NASBA and the antigenemia assay appeared to correspond poorly, a clear correlation was seen between pp67 NASBA-negative results and low numbers of pp65 antigen-positive cells. Twenty patients (59%) were treated with ganciclovir after the diagnosis of symptomatic CMV infection. Before initiation of the antiviral therapy, the antigenemia assay detected the onset of symptomatic infection in all patients, whereas 95 and 60% of these patients were IE NASBA and pp67 NASBA positive, respectively. Although the sensitivity of IE NASBA was very high, the positive predictive value (PPV) of this assay for the onset of a symptomatic infection was only 63%. The PPV of the antigenemia assay as well as pp67 NASBA was considerably higher (80 and 86%, respectively). Thus, the detection of IE mRNA using NASBA appears to be particularly useful as a marker for early initiation of antiviral therapy in patients at high risk for the development of a symptomatic infection. Also, IE NASBA was found to be more sensitive than the antigenemia assay for monitoring CMV infection during antiviral therapy. On the contrary, pp67 NASBA did not appear to have additional diagnostic value compared to the antigenemia assay.

Adult↗
PubMed1999

Antiviral and immunomodulatory effects of desferrioxamine in cytomegalovirus-infected rat liver allografts with rejection.

BACKGROUND: Cytomegalovirus (CMV) infection is associated with acute and chronic allograft rejection. We have recently shown that rat CMV increases portal inflammation and bile duct destruction in a model of rat liver allograft rejection. Desferrioxamine (DFO), an iron chelator and antioxidant, has recently been demonstrated to have antiviral as well as immunomodulatory effects in vitro. We therefore investigated whether DFO inhibits (a) CMV infection and (b) graft destruction in our rat model. METHOD: One day after liver transplantation, PVG (RT1c) into BN(RT1n), the rats were infected with rat CMV (RCMV, Maastricht strain; 10(5) plaque-forming units i.p.). The effects of 100 mg/kg body weight and 200 mg/kg body weight DFO were examined. RESULTS: In the untreated group, the grafts were uniformly RCMV culture-positive. In the group receiving 200 mg/kg DFO, RCMV replication was effectively inhibited. Inflammatory response in the graft, and especially the number of macrophages, was significantly reduced by DFO. Portal inflammation and bile duct destruction were also significantly reduced. In the untreated group, the bile duct epithelial cells were found to be strongly positive for tumor necrosis factor-alpha and this expression was clearly decreased by DFO. In addition, DFO significantly inhibited vascular cell adhesion molecule-1 expression on sinusoidal endothelial cells. CONCLUSIONS: Our in vivo transplant study strongly supports the inhibitory effects of metal chelators on CMV infection and their possible usefulness in the treatment of CMV-induced pathogenic changes.

Adjuvants, Immunologic↗
PubMed1999

Effect of desferrioxamine (DFO) and calcium trinatrium diethylenetriaminepentaacetic acid (DTPA) on rat cytomegalovirus replication in vitro and in vivo.

Cytomegalovirus (CMV) infection is a major problem in the immunosuppressed patient. It is thought that besides direct CMV induced cell lysis, immunological damage is part of CMV pathogenesis. New antiviral drugs, which combine immunomodulating and antiviral qualities, could be beneficial. Recently, it has been described that desferrioxamine (DFO) and calcium trinatrium diethylenetriaminepentaacetic acid (DTPA) exhibit both properties. In this report the antiviral effects of both compounds against rat CMV (RCMV) are described in vitro and in vivo using a generalised and local infection model. In vitro, both compounds exhibited a significant antiviral effect, DTPA being more potent than DFO. However, in the generalised infection model no effect was seen on mortality, morbidity or presence of virus in internal organs. In rats infected subcutaneously in the hind paw, no effect was seen locally on paw thickness, presence of viral antigens and inflammatory response. In addition, these rats suffered from a generalised infection of low magnitude at 15 days post infection, although both DFO and DTPA were able to lower the level of viral replication. In conclusion, our data indicate that despite in vitro activity, in vivo usage of DFO or DTPA for acute CMV infection is not warranted.

Animals↗
PubMed1999

Complement membrane attack complex and protectin (CD59) in liver allografts during acute rejection.

BACKGROUND/AIMS: The complement system is important in the rejection of xenografts, but very little is known about its activation in the rejection of allografts. Complement lysis is induced by the membrane attack complex (MAC), an aggregate of C5b, C6, C7, C8 and C9 molecules. The main defender against MAC is the CD59 molecule, also called protectin. In this study, the aim was to analyze the possible deposition of MAC and the fate of CD59 on distinct cell populations during liver allograft rejection. METHODS: Liver allografts were monitored by frequent fine-needle aspiration biopsies (FNAB) to demonstrate the immunoactivation of rejection. To examine MAC and CD59 in the FNAB, in relation to the activation markers of rejection, IL2-receptor, MHC class II and ICAM-1 expression, specific monoclonal antibodies and immunoperoxidase staining were used. RESULTS: Ten out of 21 consecutive liver transplants underwent a histologically confirmed episode of reversible acute rejection. In the FNAB, a significant increase of the activation markers IL2-receptor, class II and ICAM-1 correlated with the peak of inflammation during the episode. In association with inflammation, a significant deposition of MAC was recorded in neutrophils and lymphocytes infiltrating the graft and in the parenchymal cells. MAC deposition subsided together with the inflammation. A significant decrease in CD59 expression was seen in neutrophils during rejection, but CD59 expression on other inflammatory cells and hepatic tissue cells varied greatly. CONCLUSIONS: Complement activation was seen in association with acute rejection of liver allografts and it led to MAC assembly on leukocytes and tissue cells. A decrease in CD59 expression was less clear-cut, but it may predispose the cells to complement-mediated elimination.

Acute Disease↗
PubMed1999

Time-related effects of cytomegalovirus infection on the development of chronic renal allograft rejection in a rat model.

Cytomegalovirus (CMV) infection is a risk factor for chronic allograft rejection. The histological findings of chronic renal allograft rejection include inflammation, vascular intimal thickening, glomerulosclerosis, tubular atrophy and fibrosis. We have developed a rat model of renal transplantation in which transplants, after an early inflammatory episode, end up with chronic rejection within 60 days. During the early phase of the process in this model, CMV increased and prolonged the inflammatory response, the expression of adhesion molecules, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and their ligands, lymphocyte function antigen-1 and very late antigen-4 in the graft. Simultaneously, the production of various growth factors, such as transforming growth factor beta, platelet-derived growth factor and connective tissue growth factor was upregulated, which induce smooth muscle cell proliferation in the vascular wall and collagen synthesis by fibroblasts. Chronic rejection developed within 20 days in CMV-infected grafts. In summary, CMV infection accelerated and enhanced the early immune response, the induction of growth factors and collagen synthesis, and the development of chronic rejection in renal allografts.

Animals↗
PubMed1999

Diagnostic value of nucleic-acid-sequence- based amplification for the detection of cytomegalovirus infection in renal and liver transplant recipients.

To evaluate the diagnostic value of nucleic-acid-sequence-based amplification (NASBA) for the detection of cytomegalovirus (CMV) infection in transplant recipients, we compared immediate early 1 (IE1) and late pp67 mRNA detection by NASBA with the antigenemia assay, PCR and viral culture in 72 renal transplant (RTx) recipients and with antigenemia and serology in 25 liver transplant (LTx) recipients. Antigenemia, viral culture and pp67 NASBA were almost equivalent for the detection of CMV in RTx recipients. In LTx recipients, antigenemia detected more positive samples and more positive recipients compared to pp67 NASBA. In RTx recipients, PCR detected more positive samples and positive recipients compared to pp67 NASBA, antigenemia and viral culture. Also the first day of detection was slightly earlier for PCR. However, IE1 NASBA was the most sensitive test and detected 96% of all positive samples and positive transplant recipients. In addition, IE1 NASBA preceded PCR and all other positive results. This makes IE1 NASBA a very attractive screening test for the early detection of CMV infection.

Antigens, Viral↗
PubMed1998

An experimental model of chronic renal allograft rejection in the rat using triple drug immunosuppression.

BACKGROUND: Chronic rejection is a major problem in renal transplantation. Various experimental models have been developed to study vasculopathy of chronic rejection. However, animal models resembling the clinical situation of renal transplantation with combination therapy of basic immunosuppression are not available. The aim of this study was to find an experimental model of a donor-recipient rat strain combination that, under triple drug immunosuppressive treatment (methylprednisolone, cyclosporine, and azathioprine), would develop chronic rejection within a few weeks. METHODS: Renal transplantations were performed in strain combinations of DA-->AO, PVG-->BN, and DA-->BN. In each group, 5-8 animals received triple drug treatment of methylprednisolone (2 mg/kg), azathioprine (2 mg/kg), and cyclosporine (5 mg/kg) daily, 5-10 animals were left without treatment, and 6 syngenic transplantations were performed. The grafts were monitored with ultrasound-guided fine needle aspiration biopsies to quantify the inflammation in the graft. Graft histology was performed in parallel and quantified by using the chronic allograft damage index (CADI). RESULTS: In nonimmunosuppressed animals, irreversible acute rejection with a high peak of inflammation appeared in every strain combination within 5-8 days. In triple drug-treated rats, the DA-->AO combination demonstrated a prolonged acute rejection but no characteristic chronic changes, and the PVG-->BN combination showed practically no inflammation and did not develop any signs of chronic rejection within 60 days (CADI: 2.7+/-2.1), but the DA-->BN combination showed an early, mild inflammatory response 5-7 days after transplantation and developed chronic rejection within 40-60 days after transplantation (CADI: 7.9+/-3.1). Syngenic animals showed no inflammation or histological alterations (CADI: 1.7+/-2.0). CONCLUSIONS: In conclusion, in the DA-->BN combination with triple drug treatment, early mild inflammation was followed by the development of chronic rejection and can be used as an experimental model that resembles the clinical situation in renal transplantation.

Animals↗
PubMed1998

Cytomegalovirus infection is associated with increased inflammation and severe bile duct damage in rat liver allografts.

It has been suggested that cytomegalovirus (CMV) infection is involved in allograft rejection. In liver transplantation, it has been suggested that CMV is associated with the development of vanishing bile duct syndrome (VBDS), and persistent CMV has been found in liver grafts that develop chronic rejection. In this experimental study, the effect of rat CMV (RCMV) infection on intragraft changes was investigated in a rat model of acute liver allograft rejection. Liver transplantations were performed in a rat strain combination of PVG (RT1c) --> BN (RT1n). No immunosuppression was given. One group of animals was infected with RCMV Maastricht Strain (10(5) plaque-forming units, intraperitoneally), and another group was left uninfected. The grafts were examined histologically after the rats were killed on postoperative days 7 through 9 at the early phase and days 20 through 30 at the late phase of rejection. Immunohistochemical studies were performed to demonstrate the immunological activation markers major histocompatibility complex class II and interleukin 2 receptors, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and their ligands. RCMV infection was demonstrated from the grafts by culture and direct antigen detection. In liver allografts undergoing acute rejection, CMV significantly increased portal inflammation and caused more severe bile duct damage than in the uninfected grafts. CMV was also linked to the induction of VCAM-1 in the endothelial cells. The ongoing infection was found to vary over time in the different structures of the liver grafts, including the vascular endothelium and bile ducts. Our results support an association between CMV infection and the immunological mechanisms of rejection, as well as the role of CMV in the development of bile duct damage in liver allografts.

Animals↗
PubMed1998

CMV infection detected in the upper gastrointestinal tract after liver transplantation.

As a pilot series on the frequency of gastroduodenal cytomegalovirus (CMV) involvement after liver transplantation, we examined forceps biopsies of 13 consecutive patients who underwent esophagogastroduodenoscopy during the first 3 months after transplantation. CMV was demonstrated in frozen sections by monoclonal antibody and immunoperoxidase staining. In parallel, peripheral blood was examined for CMV pp65 antigenemia. CMV antigens were detected in biopsies of ten patients, in ten cases in the duodenum and in four in the stomach. At the time of endoscopy, sic patients had CMV antigenemia, five of them had a simultaneous positive finding in the duodenum. Although all ten patients with the positive biopsy finding had some gastrointestinal symptoms, only one had severe enteritis. In liver transplant patients, CMV was commonly detected in leukocytes located in the mucosa of the upper gastrointestinal tract, especially in the duodenum. Further investigation is needed to determine the significance of positive CMV findings in the biopsies and their association with the development of severe gastrointestinal symptoms.

Biopsy↗
PubMed1998

Ganciclovir prophylaxis after lung and heart-lung transplantation.

Cytomegalovirus (CMV) infection causes both acute and chronic allograft damage. The aim of this study was to analyze the utility of ganciclovir in preventing CMV infection in pulmonary allografts. Thirty five consecutive lung (LTX) and heart-lung (HLTX) transplant patients were studied from 1990 to 1996. CMV prophylaxis was started in January 1995. Recipients with CMV-positive serology received ganciclovir on postoperative days (POD) 7-28. Acyclovir was given on POD 29-90. Recipients with CMV-negative serology received ganciclovir on POD 7-90 if the serology of the donor was positive. CMV was demonstrated by rapid cell vial culture and/or detecting CMV-specific antigens in bronchoalveolar lavage (BAL) samples. The time point of the first BAL fluid specimen exhibiting CMV was estimated using the Life Table method. BAL samples of all the recipients without ganciclovir treatment became positive for CMV, whereas two of the 11 patients with ganciclovir administration remained negative. Ganciclovir significantly (P < 0.05) delayed but did not absolutely prevent CMV infection after LTX and HLTX.

Adolescent↗