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Biomedical subjects

M G Michaels

Publications and source records attributed to M G Michaels.

At least 19 recordsLinked to original sources
PubMed2006

CMV-IVIG for prevention of Epstein Barr virus disease and posttransplant lymphoproliferative disease in pediatric liver transplant recipients.

A randomized controlled trial of CMV-IVIG (cytomegalovirus-intravenous immunoglobulin) for prevention of Epstein Barr virus (EBV) posttransplant lymphoproliferative disease (PTLD) in pediatric liver transplantation (PLTx) recipients was begun in Pittsburgh and subsequently expanded to four additional sites. Protocol EB viral loads were obtained in a blinded fashion; additional loads could be obtained for clinical indications. Patients were followed for 2 years post-LTx. Eighty-two evaluable patients (39 CMV-IVIG, 43 placebo) developed 18 episodes of EBV disease (7 CMV-IVIG, 11 placebo) including nine cases of PTLD (three CMV-IVIG, six placebo). No significant differences were seen in the adjusted 2-year EBV disease-free rate (CMV-IVIG 79%, placebo 71%) and PTLD-free rate (CMV-IVIG 91%, placebo 84%) between treatment and placebo groups at 2 years (p > 0.20). The absence of significant effect of CMV-IVIG may be explained by a lack of efficacy of the drug or limitations of sample size.

Adolescent↗
PubMed2003

Nonhuman primate herpesviruses: importance for xenotransplantation.

Herpesviruses are found throughout the animal kingdom. Members of this family share properties including a highly orchestrated system of transcription, destruction of the host cell by active viral replication and an ability to persist in the host in a latent form. Human herpesviruses have all been implicated in causing substantial disease after allotransplantation. Often transmission of these viruses has been through the donor organ or blood products. Analogous species of herpesviruses exist in nonhuman primates. Accordingly, concern regarding the risk of their transmission and disease exists with xenotransplant procedures. This chapter reviews herpesviruses of nonhuman primates and their potential implication for causing disease after xenotransplantation.

Animals↗
PubMed2001

Detection of infectious baboon cytomegalovirus after baboon-to-human liver xenotransplantation.

Xenotransplantation is considered to be a solution for the human donor shortage. However, there is a potential risk of transmitting animal infections from the transplanted organ. The known transmissibility and clinical significance of human cytomegalovirus (HCMV) infection after allotransplantation led us to evaluate whether baboon cytomegalovirus (BCMV) transmission could occur after a baboon-to-human liver xenotransplant. We examined serial blood samples from a baboon liver recipient and isolated replication-competent CMV-like agents on days 29, 36, and 42 after xenotransplantation. BCMV and HCMV DNAs were detected in the day 29 isolate, while only HCMV DNA was detected in the other isolates. This is the first report of detecting a replication-competent virus from a source animal after xenotransplantation and is a concern with regard to potential zoonotic transmission to others.

Adult↗
PubMed1999

The management of Epstein-Barr virus associated post-transplant lymphoproliferative disorders in pediatric solid-organ transplant recipients.

Despite a growing understanding of the pathogenesis and spectrum of Epstein-Barr virus (EBV) and EBV-associated post-transplant lymphoproliferative disease (PTLD) in organ transplant recipients, the optimal management of this complication remains controversial. The absence of comparative data evaluating potential therapeutic strategies explains the lack of uniformly accepted guidelines for the management of PTLD. The purpose of this review is to provide an overview of potential therapies and offer a set of guidelines for the management of EBV-associated PTLD in children.

Antiviral Agents↗
PubMed1998

Amplification of simian retroviral sequences from human recipients of baboon liver transplants.

Investigations into the use of baboons as organ donors for human transplant recipients, a procedure called xenotransplantation, have raised the specter of transmitting baboon viruses to humans and possibly establishing new human infectious diseases. Retrospective analysis of tissues from two human transplant recipients with end-stage hepatic disease who died 70 and 27 days after the transplantation of baboon livers revealed the presence of two simian retroviruses of baboon origin, simian foamy virus (SFV) and baboon endogenous virus (BaEV), in multiple tissue compartments. The presence of baboon mitochondrial DNA was also detected in these same tissues, suggesting that xenogeneic "passenger leukocytes" harboring latent or active viral infections had migrated from the xenografts to distant sites within the human recipients. The persistence of SFV and BaEV in human recipients throughout the posttransplant period underscores the potential infectious risks associated with xenotransplantation.

Adult↗
PubMed1998

Non-aspergillus allergic bronchopulmonary mycosis in a pediatric patient with cystic fibrosis.

This article describes a child with cystic fibrosis (CF) and allergic bronchopulmonary mycosis caused by Tricosporon beigelii. An 11-year-old boy with CF failed to respond to conventional treatment for a pulmonary exacerbation. Bronchial washings contained copious budding yeast forms, subsequently identified as T beigelii. Total serum immunoglobulin E was elevated and precipitating antibodies to T beigelii were positive. Together these findings support the diagnosis of allergic bronchopulmonary mycosis. The patient improved with antifungal therapy and systemic glucocorticoid therapy. The pathologic potential of yeast in the airways of patients with CF is unclear. The diagnosis of non-Aspergillus allergic bronchopulmonary mycosis requires a high degree of suspicion and has potentially important implications for the management of patients with CF.

Bronchial Diseases↗
PubMed1998

Xenotransplant-associated infections.

Xenotransplantation is considered increasingly as a solution to the current shortage of human organs for allotransplantation. In addition, it is being investigated as a treatment for a number of other diseases such as Parkinson's disease, diabetes mellitus, and acquired immunodeficiency disease. The potential risk of novel zoonotic infections is a concern associated with these procedures. Accordingly, the role of animal microbial agents must be critically examined. This review examines the concerns and proposed mechanisms for xenogeneic infections and details what is known and what still needs to be learned as the field of xenotransplantation progresses. Emphasis is placed on microbial agents of baboons and swine because they are currently the most common species considered as donor sources for xenotransplantation.

Animals↗
PubMed1997

Posttransplantation lymphoproliferative disorders in pediatric thoracic organ recipients.

OBJECTIVE: To determine the frequency, predisposing factors, clinical presentation, and outcome of posttransplantation lymphoproliferative disorders (PTLDs) in pediatric thoracic organ transplant recipients. METHODS: Retrospective review of the medical records of all 120 children who survived longer than 1 month after thoracic organ transplantation at our center. RESULTS: PTLD was diagnosed in 14 patients (11.7%), including 7.7% of heart and 19.5% of heart-lung/lung recipients. Presentation of PTLD was variable, ranging from asymptomatic lung nodules on chest radiograph to diffuse multiorgan failure. Treatment with a reduction of immunosuppression and antiviral therapy resulted in resolution of PTLD in eight patients. Eight patients died. PTLD contributed to death in five. No patient seropositive for Epstein-Barr virus (EBV) before transplantation had PTLD. There was a significant association between primary EBV infection after transplantation and the presence of PTLD. CONCLUSIONS: PTLD occurs with greater frequency in pediatric thoracic organ transplant recipients than in the adult transplant population. Primary EBV infection after transplantation is the major risk factor for the development of PTLD. Patients in whom primary EBV infection develops after transplantation should be managed with a reduction in immunosuppression and with heightened surveillance for the development of PTLD.

Adolescent↗
PubMed1997

Distinguishing baboon cytomegalovirus from human cytomegalovirus: importance for xenotransplantation.

The severe shortage of human organs for transplantation is the driving force behind xenotransplant research. Nonhuman primates, particularly baboons, are potential sources of organs and tissues. Human cytomegalovirus (HCMV) is the most common donor-associated infection after allotransplantation. Baboon cytomegalovirus (BCMV) is endemic in baboon populations and therefore is a potential cause of donor-associated disease after xenotransplantation. Accordingly, the ability for BCMV to grow in human cells was determined and a sensitive method to distinguish BCMV from HCMV was developed. Human fibroblasts were permissive for BCMV, isolates exhibited cytopathology characteristic of HCMV, and herpesvirus-like virions were observed by electron microscopy. BCMV and HCMV could be distinguished by restriction fragment length polymorphism patterns and by polymerase chain reaction with primers targeting the BCMV major immediate-early gene promoter. These methods can be used to evaluate BCMV pathogenicity in laboratory and clinical xenotransplant trials.

Animals↗
PubMed1996

Lack of susceptibility of baboons to infection with hepatitis B virus.

Historically, hepatitis B virus (HBV) has been considered species specific and unable to infect baboons. Based on this premise, two patients with HBV endstage liver disease underwent baboon liver xenotransplantation. To study whether baboons are susceptible to HBV infection, four baboons (two receiving immunosuppressive therapy) were inoculated with HBV. Animals were followed for 6 months: clinical examinations and biochemical studies were normal, hepatitis B surface antigen and hepatitis B core antigen staining of biopsies was negative, and HBV serology remained negative. HBV polymerase chain reaction was transiently positive in one animal, which most likely reflects the initial inoculation. This pilot study corroborates historical evidence and beliefs that baboons are resistant to HBV.

Animals↗
PubMed1996

Interferon-alpha affects the immune response in post-transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorder (PTLD) is associated with Epstein-Barr virus (EBV) and characterized by fever, lymphadenopathy, and graft dysfunction. We describe the clinical course of an EBV seronegative 11-yr-old boy who underwent double lung transplantation and subsequently developed PTLD in the graft. A reduction in immunosuppression and the addition of acyclovir did not result in improvement. Treatment with interferon-alpha (IFN-alpha), however, led to dramatic clinical, radiographic, and histologic improvement. Semiquantitative measurements of cytokine mRNA in his bronchoalveolar lavage cells prior to therapy with IFN-alpha revealed high levels of IL-4 and IL-10 mRNA, which decreased significantly with treatment. We speculate that the beneficial effect of IFN-alpha in the treatment of PTLD is directly related to the inhibition of type 2 helper (Th2-like) T-cells.

Bronchoalveolar Lavage Fluid↗
PubMed1995

Persistence of extrahepatic hepatitis B virus DNA in the absence of detectable hepatic replication in patients with baboon liver transplants.

The presence of hepatitis B virus (HBV) DNA in extrahepatic tissues has been well documented. Whether HBV DNA can persist in extrahepatic tissues for long periods of time in the absence of replication in the liver has not been determined previously. Recently, two patients with end-stage liver disease secondary to chronic active HBV were treated with baboon liver xenotransplants as these animals are felt to be resistant to HBV infection. Multiple tissues from these two patients were examined for HBV DNA using polymerase chain reaction (PCR). HBV DNA was not detectable in four of five samples of the liver xenografts. A positive signal was observed in a single assay for one sample, but this sample was not positive in subsequent assays. HBV DNA was detected in peripheral blood lymphocytes, spleen, kidney, bone marrow, pancreas, lymph node, heart and small intestine. The level of HBV DNA in these tissues was too low for the detection of HBV DNA replicative intermediates by Southern hybridization; thus, it could not be determined whether the HBV DNA in these tissues represented actively replicating HBV in extrahepatic sites, integrated HBV sequences, HBV in infiltrating lymphocytes, or deposition of HBV immune complexes originating from the plasma. However, it is clear from this study that HBV DNA persisted in multiple tissues for 70 days after replication in the liver had ceased or at least was below the level of detection by PCR.

Adult↗
PubMed1995

Adenovirus pneumonia in lung transplant recipients.

Although Adenovirus (ADV) pneumonia has been documented in bone marrow, kidney, and liver transplantation recipients, it has only been sporadically reported in lung transplantation recipients. Among our 308 lung transplantation recipients, we identified four who developed ADV pneumonia. Formalin-fixed paraffin-embedded biopsy and autopsy specimens on all cases were studied by routine histology, immunohistochemistry (IHC), and by in situ hybridization (ISH) for evidence of ADV, and the results were correlated with the patients' clinical progression. Three of the four patients were children, and all four had a progressive and rapidly fatal course within 45 days posttransplantation. The lungs showed necrotizing bronchocentric pneumonia with tendency to spread diffusely to produce alveolar damage and organizing pneumonia. The occurrence of this rapidly fatal ADV pneumonia mainly affecting the pediatric population, early in the posttransplantation course, suggests that the infection is primary to the recipient with ADV either originating and reactivating in the donor lung or acquired from the upper respiratory tract of the recipient. The characteristic smudgy intranuclear inclusions of ADV, as well as IHC and ISH positivity, were observed in the lungs of all autopsies. Antemortem biopsy demonstration of ADV by inclusion formation, IHC, and ISH was observed in two patients. In another patient, antemortem ADV was shown only by ISH, and the recognition of inclusions was made difficult by coexistent CMV infection. Although IHC and ISH may have the potential for detecting early infection, recognition of the characteristic clinical setting with necrotizing bronchocentric pneumonia and smudgy intranuclear inclusions should alert one to the diagnosis of ADV pneumonia.

Adenoviridae Infections↗
PubMed1994

Screening donors for xenotransplantation. The potential for xenozoonoses.

Xenotransplantation is a potential solution to the current donor shortage for solid organ transplantation. The transmission of infectious agents from donor organs or bone marrow to the recipient is a well-recognized phenomenon following allotransplantation. Thus the prospect of xenotransplantation raises the issue of xenozoonoses--i.e., the transmission of animal infections to the human host. Anticipating an increasing number of baboon to human transplants, 31 adult male baboons (Papio cynocephalus) from a single colony in the United States were screened for the presence of antibody to microbial agents (principally viral) that may pose a significant risk of infection. Antibody to simian cytomegalovirus, simian agent 8 and Epstein-Barr virus, was found in 97% of animals tested. Antibody to simian retroviruses and Toxoplasma gondii was found in 30% and 32% respectively. Discordant results were found when paired samples were examined by two primate laboratories. This was particularly noted when methodologies were based on cross-reaction with human viral antigens. These results highlight the need to develop specific antibody tests against the species used for xenotransplantation.

Animals↗