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Biomedical subjects

I Lautenschlager

Publications and source records attributed to I Lautenschlager.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1998

Human herpesvirus-6 infection after liver transplantation.

A diagnosis of posttransplantation human herpesvirus-6 (HHV-6) infection was established for eight adult recipients among a liver transplantation patient population of 121. The diagnosis was based on serology and demonstration of HHV-6 specific antigens in liver biopsy specimens with use of monoclonal antibodies and immunoperoxidase staining. A significant graft dysfunction was recorded in association with serodiagnosis. HHV-6 early antigens, as well as HHV-6 variant B antigens, were detected retrospectively in all six available liver biopsy specimens. Histologic examination of biopsy specimens demonstrated acute rejection in 5 of the 8 patients, and 3 patients had portal lymphocyte infiltration. In five cases cytomegalovirus (CMV) infection was associated with HHV-6 infection; in four cases CMV antigens were also detected in the biopsy specimens. Two patients who had pure HHV-6 infection without CMV infection or rejection had significantly impaired graft function, with a positive antigen-detection test. Thus, HHV-6 may infect the liver allograft and cause graft dysfunction and may possibly be associated with rejection and/or CMV infection.

Adult↗
PubMed1997

Effect of cytomegalovirus on an experimental model of chronic renal allograft rejection under triple-drug treatment in the rat.

BACKGROUND: Cytomegalovirus (CMV) infection is thought to be a risk factor of chronic rejection. In clinical studies and animal models, mainly concerning graft vasculopathy, CMV has been demonstrated to enhance allograft arteriosclerosis. In this study we have investigated the effect of CMV on the early inflammatory response and graft histology in an experimental model of renal transplantation in a rat strain combination that develops chronic rejection under triple-drug immunosuppression. METHODS: Renal transplantations were performed in a rat strain combination of DA-->BN receiving triple-drug treatment (2 mg/kg methylprednisolone, 2 mg/kg azathioprine, 5 mg/kg cyclosporine daily subcutaneously). One group of immunosuppressed animals was infected with rat CMV, the Maastricht strain (10(5) plaque-forming units intraperitoneally), and the other group was left uninfected. As a positive control for alloresponse, one group of recipients received neither immunosuppression nor virus. Syngenic transplantations with triple-drug treatment and CMV were used as negative controls. The grafts were monitored by frequent ultrasound-guided fine-needle aspiration biopsies, and the intragraft inflammation was quantified in detail by the increment method and expressed in corrected increment units (CIU). Graft histology was performed in parallel. RESULTS: Nonimmunosuppressed animals developed acute rejection with a high peak of inflammation (7.9+/-3.2 CIU), a typical blast response, and lymphocytosis followed by infiltration of macrophages and necrosis within 7 days. Triple drug-treated animals had a short, mild inflammatory response (3.3+/-1.4 CIU at the peak) in the graft 3-5 days after transplantation but ended up with histological changes characteristic of chronic rejection with vasculopathy and fibrosis 40-60 days later. Triple drug-treated animals with CMV demonstrated a significantly stronger inflammation (4.5+/-1.8 CIU, P<0.01) than those without, and lymphoid activation continued longer and was followed by infiltration of macrophages in the graft. CMV infection of the graft was demonstrated by viral culture and antigen detection. In histology, chronic rejection with intimal thickening of arteries and arterioles and medial necrosis of large arteries was seen at 14 days, ending up with remarkable graft fibrosis within 20 days after transplantation. CONCLUSION: CMV prolonged and increased graft inflammation and accelerated chronic rejection of renal allografts under triple-drug treatment.

Animals↗
PubMed1997

A rat model of monitoring liver allograft rejection.

Rat models are often used to study liver allograft rejection. We have established a model for rat liver allograft rejection, monitored by fine needle aspiration biopsy (FNAB), in the strain combination PVG-to-BN with a mean survival time of 37 +/- 20 days. In this model, we observed acute rejection with an intense peak of lymphoid blasts and lymphocyte-dominated inflammation in the FNAB [9.1 +/- 3.0 corrected increment units (CIU)], and an eventual increase in macrophages (up to 4.2 +/- 4.4 CIU), together with fibrosis and parenchymal necrosis in the graft. Markers of immune activation, such as an increase in IL-2-receptor (from 1% +/- 2% to 21% +/- 13%) and class II (from 20% +/- 9% to 43% +/- 13%) expressing lymphoid cells and induction of ICAM-1 in the graft, were consistent with the overall cellular response. The FNAB correlated well with parallel graft histology. In this rat model, the atraumatic monitoring makes a close follow-up possible without having to sacrifice the experimental animals. This saves work, animals, and costs in the study of liver rejection.

Animals↗