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Biomedical subjects

D R Carrigan

Publications and source records attributed to D R Carrigan.

At least 37 records · Page 2Linked to original sources
PubMed1995

Fulminant human herpesvirus six encephalitis in a human immunodeficiency virus-infected infant.

Self-limited involvement of the central nervous system (CNS) is a relatively common complication of primary infection with human herpesvirus six (HHV-6) in normal children. We describe an HIV-infected infant who developed fulminant encephalitis as a complication of HHV-6 infection. Immunohistochemical staining of CNS tissue demonstrated productive infection of all CNS cell-types. Analysis of the infected brain tissue by the polymerase chain reaction (PCR) confirmed the presence of a dense HHV-6 infection in the tissue, and demonstrated that the virus present in the CNS tissue was predominantly the A variant of HHV-6. This is the first demonstration of invasive tissue disease caused by HHV-6 in an HIV-infected infant.

AIDS-Related Opportunistic Infections↗
PubMed1995

Progressive immunodeficiency and fatal pneumonitis associated with human herpesvirus 6 infection in an infant.

Human herpesvirus 6 (HHV-6), an important opportunistic pathogen in immunocompromised patients, causes fatal pneumonitis, encephalitis, and bone marrow suppression. Its ability to infect and destroy T lymphocytes may allow it to synergize with the human immunodeficiency virus in the destruction of lymphoid tissues in patients with AIDS. We describe herein an infant who had an immunodeficiency associated with thymic atrophy and severe T lymphocytopenia who developed fatal pneumonitis due to HHV-6. Dense and disseminated infection of T lymphocytes with HHV-6 was also documented. In the absence of any other documented cause of immunodeficiency, we hypothesize that congenital infection of this infant with HHV-6 may have caused progressive destruction of her cellular immune system, leading to the fatal pneumonitis. Thus, HHV-6 infection may have been the cause of both her immunodeficiency and her fatal opportunistic infection.

Atrophy↗
PubMed1995

Detection of human herpesvirus 6 in plasma of children with primary infection and immunosuppressed patients by polymerase chain reaction.

A sensitive and specific polymerase chain reaction method for the detection of human herpesvirus 6 (HHV-6) DNA in serum or plasma has been developed. In total, 157 human serum or plasma samples were studied. HHV-6 DNA was detected in 6 (85.7%) of 7 children with exanthem subitum, 3 (23.1%) of 13 bone marrow transplant (BMT) recipients, 4 (22.2%) of 18 human immunodeficiency virus (HIV)-infected patients, 1 (2.6%) of 39 patients with chronic fatigue syndrome, and none of 37 healthy adults. In the HHV-6-positive BMT recipients, HHV-6 plasma DNA was transiently detected during episodes of fever and respiratory infection. In children with exanthem subitum and in 1 HIV-infected patient, the HHV-6 strains were characterized as variant B, whereas variant A was detected in all other patients. Detection of viral DNA in serum or plasma is a marker of active infection that can be used to investigate the role of HHV-6 in human disease.

Adult↗
PubMed1995

Chronic myelopathy associated with human herpesvirus-6.

Human herpesvirus-6 (HHV-6) is implicated in a variety of neurologic diseases. We report a previously healthy elderly woman with progressive spastic paraparesis. At autopsy the spinal cord showed widespread demyelination, axonal loss, and chronic inflammation. HHV-6 DNA was amplified, using polymerase chain reaction, from spinal cord tissue, and glial cells were immunoreactive with an HHV-6 antibody. These findings suggest that HHV-6 may cause myelopathy.

Aged↗
PubMed1995

Effect of dispenser location on taking free condoms in an outpatient cocaine abuse treatment clinic.

Crack cocaine use increases risky sexual behavior and HIV exposure; therefore, safe sexual practices should be encouraged during cocaine addiction treatment. Research indicates that placing condom dispensers in private restrooms increases taking free condoms. We investigated two other dispenser locations (a day room vs. counselors' offices) and found that substantially more condoms were taken when dispensers were in the day room. This is an important issue for public health facilities without private restrooms.

Journal Article↗
PubMed1995

Late graft failure due to dual bone marrow infection with variants A and B of human herpesvirus-6.

Hematopoietic effects of human Herpesvirus-6 (HHV-6) infection following bone marrow transplantation (BMT) include delayed engraftment and early myelosuppression. Variant A has not been isolated after BMT. A case of graft failure is reported following an HLA-identical BMT for chronic myelogenous leukemia (CML) in chronic phase. Evaluation of bone marrow during the period of graft failure revealed variants A and B of HHV-6 by culture, immunofluorescence, polymerase chain reaction (PCR), and immunohistochemistry. Evidence for other cases of graft failure, including cytomegalovirus (CMV), could not be found. A hypothesis is proposed that late graft failure in this case was due to variant A of HHV-6.

Adult↗
PubMed1994

Human herpesvirus 6 (HHV-6) isolation from bone marrow: HHV-6-associated bone marrow suppression in bone marrow transplant patients.

These studies tested the hypothesis that human herpesvirus 6 (HHV-6) can cause posttransplant bone marrow (BM) suppression in BM transplant (BMT) patients. Fifteen adult patients who received T-lymphocyte-depleted, allogeneic BM transplants and who developed posttransplant BM suppression were studied. Detailed chart reviews were used to divide the patients into two groups: (1) those with diagnosed BM suppression (DBMS) and (2) those with idiopathic BM suppression (IBMS). BM aspirates obtained from the patients at the onset of BM suppression were subjected to an HHV-6 isolation procedure using mitogen-stimulated blood mononuclear cells. BM specimens obtained from another population of BMT patients solely to document engraftment irrespective of their BM function were also subjected to the HHV-6 isolation procedure as controls. HHV-6 was isolated from 6 of 15 BM samples from BMT patients with BM suppression. BM samples from patients with IBMS were more likely to be positive for HHV-6 than those from patients with DBMS (P < .01). Also, HHV-6-positive BM were significantly more likely (P < .05) to come from patients with suppression of more than one BM lineage than HHV-6-negative BM. Finally, samples of BM from an unselected series of BMT patients studied without regard to their BM function were less likely (P < .01) to be positive for HHV-6 than patients with IBMS.

Adult↗
PubMed1994

Disseminated active HHV-6 infections in patients with AIDS.

Human herpesvirus 6 (HHV-6) infected cells were detected in all lung, lymph-node, spleen, liver, and kidney tissues obtained at necropsy from an unselected series of nine patients with AIDS. This infection rate was significantly higher than that for cytomegalovirus. Lung infection with HHV-6 was extensive enough in one patient to account for fatal pneumonitis. In other tissues increased numbers of HHV-6 infected cells were related to the presence of lymphocytes infiltrates or residual lymphoid tissue, with lymphocytes being predominantly infected. Thus HHV-6 is an important pathogen in patients with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1994

Human herpesvirus-6-associated malignant lymphoma in a bone marrow transplant recipient.

BACKGROUND: Human herpesvirus-6 (HHV-6), the sixth member of the herpesvirus family, can infect and replicate in human hematopoetic cell lines and can cause various illnesses in humans. HHV-6 has been suggested to be linked to various lymhoproliferative disorders. In vitro studies have demonstrated the oncogenic potential of HHV-6. The role of HHV-6 in human lymphomas needs to be examined. OBJECTIVE: To determine the involvement of HHV-6 in an immunoblastic lymphoma which developed in a bone marrow transplant patient, who had HHV-6 viremia. STUDY DESIGN: Paraffin-embedded lymphoma tissues were examined for the presence of HHV-6 by immunohistochemistry, PCR and in-situ hybridization. This is a case report investigation. RESULTS: An acute myelogenous leukemia patient received an allogeneic bone marrow transplant. He developed human herpesvirus-6 (HHV-6) viremia approximately 6 weeks after transplantation and HHV-6 was concurrently isolated from his bone marrow. Soon afterward, a large cell immunoblastic lymphoma was diagnosed. Complications of this tumor subsequently resulted in the patient's death. Periaortic lymph nodes and tumor cells infiltrating the liver and kidneys showed the presence of HHV-6 by immunohistochemistry and polymerase chain reaction (PCR). Southern blot analysis of the PCR amplified DNAs confirmed the presence of transforming pZVH14 DNA sequences of HHV-6 in the tumor tissues. Lymph nodes of 6 immunologically intact individuals were negative for HHV-6 by immunohistochemistry and PCR analysis. Tumor tissues were negative for EBV DNA by in situ hybridization with DNA probes specific for the EBV EBER RNAs. CONCLUSION: Our data suggest that HHV-6 may be involved in the pathogenesis of some immunoblastic lymphomas.

Journal Article↗
PubMed1994

Increasing incidence of adenovirus disease in bone marrow transplant recipients.

Adenovirus infections in 201 bone marrow transplant (BMT) recipients over 4 years were retrospectively reviewed. Forty-two patients (20.9%) had positive adenovirus cultures after BMT. There was a higher incidence of adenovirus infections in pediatric patients than in adults (31.3% vs. 13.6%, P = .003). In addition, the time of onset of adenovirus infection after transplant was earlier in pediatric patients (mean, < 30 days) than in adults (> 90 days). Adenovirus type 35 was the most common serotype identified. One-third of adenovirus-positive patients had definite or probable adenovirus disease. Moderate to severe acute graft-versus-host disease and isolation of adenovirus from two or more sites were significant risk factors for adenovirus disease. This report documents a higher incidence of both adenovirus infection and disease than do previous studies. Adenovirus may emerge as a more frequent pathogen as more high-risk BMT transplants are done.

Adenovirus Infections, Human↗
PubMed1993

Human herpesvirus-6-associated suppression of growth factor-induced macrophage maturation in human bone marrow cultures.

Cultures of marrow mononuclear cells were exposed to medium derived from cell cultures infected with several different strains of human herpesvirus-6 (HHV-6) immediately before the addition of either of two growth factors, granulocyte-macrophage colony-stimulating factor and interleukin-3. Exposure to any of the viral preparations suppressed the outgrowth of nonspecific esterase-positive adherent macrophages induced by the factors by more than 90%. The nonadherent cell populations in the infected cultures were numerically similar to those in uninfected control cultures, demonstrating the absence of a nonspecific cytotoxic effect of the viral materials. Infectious virus was not necessary for the macrophage outgrowth suppression. These findings suggest that HHV-6 either encodes or induces a soluble mediator or mediators that can interfere with the responses of bone marrow to growth factors and possibly block the normal differentiation of macrophages from marrow precursors.

Animals↗
PubMed1993

Human herpesvirus 6 (HHV-6)-associated dysfunction of blood monocytes.

HHV-6 is a recently described member of the herpesvirus family. HHV-6-associated marrow failure and interstitial pneumonitis where macrophages are the primary infected cell type have been described in marrow transplant patients (Carrigan, 1991; Drobyski et al., 1993). In recent studies we have shown that exposure of normal human marrow to HHV-6GS (a type A strain) or several type B strains resulted in suppression of growth factor induced outgrowth of macrophages by > 90% (Burd and Carrigan, 1993). Additional experiments using HHV-6GS to characterize the effects of the virus on peripheral blood monocytes showed that the respiratory burst capacity of these cells as determined by luminol-enhanced chemiluminescence using phorbol myristate acetate as a trigger was decreased by 83% +/- 13% in a series of 5 experiments. The decreased respiratory burst was evident as early as 15 min after exposure to virus. Experiments in which cells were separated on a fluorescence activated cell sorter prior to respiratory burst assay showed that the response was mediated solely by peripheral blood monocytes. The respiratory burst response of virus-exposed cells to opsonized zymosan was not affected, indicating that the virus may selectively interfere with the protein kinase C pathway of cellular activation. Ultracentrifugation of stock material to remove infectious virus showed that the suppressive factor was associated with the supernatant fraction. These findings suggest that HHV-6 infection may be associated with a defect in one of the major monocyte activation pathways, and this could be of importance with respect to persistent infection by HHV-6 in immune compromised patients.

Herpesviridae Infections↗
PubMed1993

Human herpesvirus-6 (HHV-6) infection in allogeneic bone marrow transplant recipients: evidence of a marrow-suppressive role for HHV-6 in vivo.

Sixteen adults were studied for the first 100 days after allogeneic bone marrow transplant to assess the pathogenic role of human herpesvirus-6 (HHV-6) infection in patients with unexplained febrile illnesses. HHV-6 was directly isolated from the blood of 6 patients. Analysis of the clinical courses of these 16 patients revealed otherwise unexplained posttransplant marrow suppression in 5 patients. Idiopathic marrow suppression occurred more frequently in patients with concurrent HHV-6 viremia (4/6) than in those from whom HHV-6 was not isolated from peripheral blood (1/10, P < .05). An etiologic role for the virus was also supported by isolation of HHV-6 from the bone marrow of all 4 patients at the time of marrow suppression and by in vitro colony-forming unit (cfu) assays that demonstrated that HHV-6 could inhibit cfu-granulocyte-macrophage and burst-forming unit-erythroid growth from human bone marrow. By restriction enzyme mapping, all clinical isolates were type B, suggesting that bone marrow transplant recipients may be preferentially infected with and reactivate this HHV-6 subtype. This study implicates HHV-6 as a novel cause of bone marrow suppression in marrow transplant recipients.

Adult↗
PubMed1993

Two groups of human herpesvirus 6 identified by sequence analyses of laboratory strains and variants from Hodgkin's lymphoma and bone marrow transplant patients.

Fifteen human herpesvirus 6 (HHV-6) strain variants were analysed by PCR amplifications, restriction enzyme site polymorphism and sequence analyses. Three DNA regions were chosen for study: a fragment of a variable glycoprotein gene (210 bp), the conserved glycoprotein H (gH) gene complete with intergenic sequences (2381 bp) and the 5' intergenic region with the N-terminal coding sequence of gH up to a polymorphic BamHI site (427 bp). Infected cell DNA from five laboratory reference strains including GS, U1102, AJ, Z29 and KF were examined together with DNA from peripheral blood lymphocytes infected with HHV-6 reactivated from blood and/or marrow from five bone marrow transplant (BMT) patients. Separate blood and marrow isolates were obtained from four BMT patients. In addition, HHV-6 sequences were examined directly from one of six Hodgkin's lymphomas and six B cell proliferations which contained HHV-6 DNA as detected by PCR amplification. The results show two groups of very closely related but heterogeneous strains which correlate with previous groupings by antigenic and restriction site differences. These are variant A strains (including laboratory strains GS, U1102 and AJ) and variant B strains (including laboratory strains Z29 and KF, the Hodgkin's lymphoma strain, and the nine BMT patient isolates). Variations between the groups were 4 to 6% in nucleotide sequence and 5 to 8.5% in amino acid sequence. Within each group maximum heterogeneity was observed in different genes. Variant A strains differed by 2.0% in the variable glycoprotein gene sequence whereas variant B strains were identical in this region; conversely, variant B strains differed by 2 to 3% in the gH N-terminal and intergenic sequences whereas variant A strains differed there by less than 0.2%. There was evidence for sequence drift independent of selection: relationships between the groups were shown by analyses of amino acid sequence, coding nucleotide sequence as well as intergenic sequence, and the B variant-specific BamHI site in the gH gene was due to a non-coding nucleotide substitution. There was little evidence for in vivo or in vitro variation: the gH nucleotide sequence from the uncultured lymphoma strain (first variant B gH gene identified) was almost identical to the gH sequence from four BMT isolates, and matched BMT isolates from blood and marrow were identical or with a single nucleotide substitution.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗