Biomedical subjects

Michael Green

Publications and source records attributed to Michael Green.

60 records · Page 4Linked to original sources

PubMed2002

Posttransplant lymphoproliferative disorders in liver transplantation: a 20-year experience.

OBJECTIVE: To evaluate the incidence of posttransplant lymphoproliferative disease (PTLD) and the risk factors and the impact of this complication on survival outcomes in a large cohort of liver transplant recipients at a single institution. SUMMARY BACKGROUND DATA: Liver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease since 1983, in large part due to the availability and reliance on the use of nonspecifically directed immunosuppression. However, as predicted and subsequently verified in 1968, an increased incidence of certain de novo malignancies has been observed, particularly with regards to lymphoid neoplasms. While many reports have confirmed and clarified the nature of PTLD, the literature is fraught with conflicting experience and outcomes with PTLD. METHODS: Four thousand consecutive patients who underwent liver transplants between February 1981 and April 1998 were included in this analysis and were followed to November 2001. The effect of recipient age at the time of transplant, recipient gender, diagnosis, baseline immunosuppression, grading of PTLD, and association with Epstein-Barr virus were compared. The causes of death were also examined. Treatment for PTLD varied over the 20-year period, but all included massive reduction or elimination of baseline immunosuppression. RESULTS: The 1-year patient survival for liver transplant patients with PTLD was 85%, while the overall patient survival for the entire cohort was 53%. The actuarial 20-year survival was estimated at 45%. The overall median time to PTLD presentation was 10 months, and children had an incidence of PTLD that was threefold higher than adults. Patient survival was better in children, in patients transplanted in the era of tacrolimus immunosuppression, in patients with polymorphic PTLD, and in those with limited disease. Interestingly, neither the presence or absence of Epstein-Barr virus nor the timing of PTLD presentation appeared to influence overall patient survival. Patients transplanted for alcohol-related liver disease had a similar incidence of PTLD but had a higher risk of mortality. CONCLUSIONS: While PTLD continues to pose problems in patients receiving liver transplants, improvements in patient survival have been observed over time. While it is too early to assess the impact of new advances in prophylaxis, diagnosis, and treatment, such approaches are based on an increased knowledge of the pathophysiology of PTLD.

Adult↗

PubMed2002

Tularemia.

Francisella tularensis is the etiological agent of tularemia, a serious and occasionally fatal disease of humans and animals. In humans, ulceroglandular tularemia is the most common form of the disease and is usually a consequence of a bite from an arthropod vector which has previously fed on an infected animal. The pneumonic form of the disease occurs rarely but is the likely form of the disease should this bacterium be used as a bioterrorism agent. The diagnosis of disease is not straightforward. F. tularensis is difficult to culture, and the handling of this bacterium poses a significant risk of infection to laboratory personnel. Enzyme-linked immunosorbent assay- and PCR-based methods have been used to detect bacteria in clinical samples, but these methods have not been adequately evaluated for the diagnosis of pneumonic tularemia. Little is known about the virulence mechanisms of F. tularensis, though there is a large body of evidence indicating that it is an intracellular pathogen, surviving mainly in macrophages. An unlicensed live attenuated vaccine is available, which does appear to offer protection against ulceroglandular and pneumonic tularemia. Although an improved vaccine against tularemia is highly desirable, attempts to devise such a vaccine have been limited by the inability to construct defined allelic replacement mutants and by the lack of information on the mechanisms of virulence of F. tularensis. In the absence of a licensed vaccine, aminoglycoside antibiotics play a key role in the prevention and treatment of tularemia.

Animals↗

PubMed2002

Detection of Epstein-Barr virus genomes in peripheral blood B cells from solid-organ transplant recipients by fluorescence in situ hybridization.

Resolution of Epstein-Barr Virus (EBV) infection in pediatric solid-organ transplant recipients often leads to an asymptomatic carrier state characterized by a persistently elevated circulating EBV load that is 2 to 4 orders of magnitude greater than the load typical of healthy latently infected individuals. Elevated EBV loads in immunosuppressed individuals are associated with an increased risk for development of posttransplant lymphoproliferative disease. We have performed fluorescence in situ hybridization (FISH) studies with peripheral blood B cells from carriers of persistent EBV loads in order to directly quantitate the number of EBV genomes per infected cell. Patients were assigned to two groups on the basis of the level of the persistent load (low-load carriers, 8 to 200 genomes/10(5) peripheral blood lymphocytes; high-load carriers, >200 genomes/10(5) peripheral blood lymphocytes). FISH analysis revealed that the low-load carriers predominantly had circulating virus-infected cells harboring one or two genome copies/cell. High-load carriers also had cells harboring one or two genome copies/cell; in addition, however, they carried a distinct population of cells with high numbers of viral genome copies. The increased viral loads correlated with an increase in the frequency of cells containing high numbers of viral genomes. We conclude that low-load carriers possess EBV-infected cells that are in a state similar to normal latency, whereas high-load carriers possess two populations of virus-positive B cells, one of which carries an increased number of viral genomes per cell and is not typical of normal latency.

Adolescent↗

PubMed2002

Current management strategies for the prevention and treatment of cytomegalovirus infection in pediatric transplant recipients.

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality following transplantation, especially in the pediatric population, who remain at high risk of primary infection. The availability of effective antiviral therapy has led to dramatic improvements in the outcome of CMV infection in patients undergoing transplantation. In recent years, three major strategies have been developed for the prevention of CMV disease in this population: reduction of risk of viral acquisition or reactivation by management of risk factors; prophylaxis of all 'at-risk' patients using prophylactic strategies for a defined period of time, initiated at or near the time of transplant; and pre-emptive treatment with ganciclovir of selected 'at-risk' patients, guided by either laboratory markers indicative of subclinical infection or the presence of specific risk factors. In general, well designed comparative studies of one or more antiviral agents for the prevention of CMV have not been carried out. While ganciclovir appears to be more effective than aciclovir, its tolerability profile is less optimal. The use of foscarnet avoids myelosuppresions, but is associated with significant nephrotoxicity. Its use should be reserved for patients unable to tolerate ganciclovir or with ganciclovir-resistant CMV disease. Similar to foscarnet, the high frequency of nephrotoxicity associated with the use of cidofovir limits its use to clinical scenarios suggestive of ganciclovir resistance. Newer options, such as valaciclovir and valganciclovir, are currently under investigation and preliminary experience has been promising. Finally, passive immunoprophylaxis has been shown to prevent CMV disease after solid organ transplantation, but its use in bone marrow transplantation is controversial. Essentially, pre-emptive strategies have relied on the quantitation in the peripheral blood of CMV phosphoprotein pp65 antigen and/or the polymerase chain reaction assay. Strict guidelines for the use of those assays as a guide to pre-emptive therapy have not been standardized. Prospective trials comparing pre-emptive therapy using either intravenous or oral ganciclovir, and now oral valganciclovir or valaciclovir, are necessary to determine the relative cost effectiveness and efficacy of these alternative strategies. Finally, it remains controversial as to whether prophylaxis or pre-emptive therapy is the optimal strategy for preventing CMV disease. While a growing body of literature describes these approaches in adult transplant recipients, published experience in children has been much more limited.

Antiviral Agents↗

PubMedDate not supplied

Impact of risperidone versus haloperidol on activities of daily living in the treatment of refractory schizophrenia.

Risperidone has been shown to improve verbal working memory, executive functioning, attention, reaction time, and verbal learning, which, in turn, have been associated with improved functional outcomes. We tested whether risperidone was associated with greater improvements than haloperidol in activities of daily living (ADLs) among persons having treatment-refractory schizophrenia. In a double-blind, controlled trial of fixed and flexible doses of haloperidol and risperidone, changes in ADLs were operationally monitored on a behavior therapy unit of a state hospital. While no differential effects were noted between risperidone and haloperidol in ADLS, these self-care skills significantly improved as subjects spent longer times on the behavior therapy unit. Working memory and verbal learning did correlate with improvements in ADLs, independent of drug condition. The contingencies of reinforcement and specific training programs on the behavior therapy unit may have been prepotent for the learning of ADLs, obscuring any differential impact of risperidone. Moreover, ADLs may be governed more by "procedural" learning than by working memory or verbal learning, with the former not differentially influenced by typical verus atypical antipsychotics.

Activities of Daily Living↗

PubMedDate not supplied

Classification of M nontypeable group A streptococcus with the use of field inversion gel electrophoresis.

Group A streptococcus (GAS) are traditionally classified based on M and T protein antigens. However, many strains do not react with available M antisera and are classified as M nontypeable (M NT). M and T typing, field inversion gel electrophoresis (FIGE), and 5' emm gene sequencing were performed on 24 M NT GAS isolates. FIGE patterns of the M NT isolates were compared by visual inspection and by computer analysis with the patterns of 139 isolates representing 72 M-types of GAS. Seven different FIGE patterns (I-VII) were seen among the M NT isolates. FIGE patterns I and III were identical or closely related to patterns seen with M12 and M22 isolates. The computer analysis determined the following relationships: pattern IV to M5, pattern VI to M61, and pattern VII to M59. Thus, the emm gene sequence correlated with the computer analysis of the FIGE pattern for each isolate. FIGE can be useful to help distinguish clinical isolates of GAS in an epidemiological study.

DNA, Bacterial↗