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Biomedical subjects

R B Mann

Publications and source records attributed to R B Mann.

At least 19 recordsLinked to original sources
PubMed2003

Chaos in a relativistic 3-body self-gravitating system.

We consider the 3-body problem in relativistic lineal [i.e., (1+1)-dimensional] gravity and obtain an exact expression for its Hamiltonian and equations of motion. While general-relativistic effects yield more tightly bound orbits of higher frequency compared to their nonrelativistic counterparts, as energy increases we find in the equal-mass case no evidence for either global chaos or a breakdown from regular to chaotic motion, despite the high degree of nonlinearity in the system. We find numerical evidence for mild chaos and a countably infinite class of nonchaotic orbits, yielding a fractal structure in the outer regions of the Poincaré plot.

Journal Article↗
PubMed2002

Statistical mechanics of relativistic one-dimensional self-gravitating systems.

We consider the statistical mechanics of a general relativistic one-dimensional self-gravitating system. The system consists of N particles coupled to lineal gravity and can be considered as a model of N relativistically interacting sheets of uniform mass. The partition function and one-particle distribution functions are computed to leading order in 1/c where c is the speed of light; as c --> infinity results for the nonrelativistic one-dimensional self-gravitating system are recovered. We find that relativistic effects generally cause both position and momentum distribution functions to become more sharply peaked, and that the temperature of a relativistic gas is smaller than its nonrelativistic counterpart at the same fixed energy. We consider the large-N limit of our results and compare this to the nonrelativistic case.

Journal Article↗
PubMed2001

Long-term results of blood and marrow transplantation for Hodgkin's lymphoma.

PURPOSE: To evaluate the long-term outcome after allogeneic (allo) and autologous (auto) blood or marrow transplantation (BMT) in patients with relapsed or refractory Hodgkin's lymphoma (HL). PATIENTS AND METHODS: We analyzed the outcome of 157 consecutive patients with relapsed or refractory HL, who underwent BMT between March 1985 and April 1998. Patients <or= age 55 with HLA-matched siblings were prioritized toward allo BMT. The median age was 28 years (range, 13 to 52 years) for the 53 allo patients and 30.5 years (range, 11 to 62 years) for the 104 auto patients. RESULTS: The median follow-up after BMT for surviving patients was 5.1 years (range, 1 to 13.8 years). For the entire group, the probabilities of event-free survival (EFS) and relapse at 10 years were 26% (95% confidence interval [CI], 18% to 33%) and 58% (95% CI, 48% to 69%), respectively. According to multivariate analysis, disease status before BMT (sensitive relapse if responding to conventional-dose therapy or resistant disease if not) (hazard ratio [HR] = 0.39, P < .0001) and date of BMT (HR = 0.93, P = .004) were independent predictors of EFS, whereas only disease status (HR = 0.35, P < .0001) influenced relapse. There was a trend for probability of relapse in sensitive patients to be less after allo BMT at 34% (range, 8% to 59%) versus 51% (range, 36% to 67%) for the auto patients (HR = 0.51, P = .17). There was a continuing risk of relapse or secondary acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) for 12 years after auto BMT, whereas there were no cases of secondary AML/MDS or relapses beyond 3 years after allo BMT. CONCLUSION: There seems to be a clinical graft-versus-HL effect associated with allo BMT. Allo BMT for HL also seems to have a lower risk of secondary AML/MDS than auto BMT. Thus, allo BMT warrants continued study in HL.

Adolescent↗
PubMed2001

Primary cutaneous T-cell-rich B-cell lymphoma: clinically distinct from its nodal counterpart?

The cases of two patients with Stage IE primary cutaneous T-cell-rich B-cell lymphoma (TCRBCL) are described. In both, the lesion showed a dense infiltrate by numerous small T lymphocytes with scattered histiocytes and large atypical B-lymphoid cells. Polymerase chain reaction assays demonstrated that the B cells were monoclonal, with immunoglobulin heavy-chain gene rearrangement. No clonal rearrangements of the T-cell receptor gamma gene were observed. Both patients were disease-free at 4 months and at 5 years after therapy, respectively. Although rare, primary cutaneous T-cell-rich B-cell lymphoma appears to have a better prognosis than its nodal counterpart, with or without skin involvement.

Antigens, CD20↗
PubMed2001

Birds disperse ixodid (Acari: Ixodidae) and Borrelia burgdorferi-infected ticks in Canada.

A total of 152 ixodid ticks (Acari: Ixodidae) consisting of nine species was collected from 82 passerine birds (33 species) in 14 locations in Canada from 1996 to 2000. The Lyme disease spirochete Borrelia burgdorferi Johnson, Schmidt, Hyde, Steigerwaldt & Brenner was cultured from the nymph of a blacklegged tick, Ixodes scapularis Say, that had been removed from a common yellowthroat, Geothlypis trichas L., from Bon Portage Island, Nova Scotia. As a result of bird movement, a nymphal I. scapularis removed from a Swainson's thrush, Catharus ustulatus incanus (Godfrey), at Slave Lake, Alberta, during spring migration becomes the new, most western and northern record of this tick species in Canada. Amblyomma longirostre Koch, Amblyomma sabanerae Stoll, and Ixodes baergi Cooley & Kohls are reported for the first time in Canada. Similarly, Amblyomma americanum L., Arnblyomma maculatum Koch, and ixodes muris Bishopp & Smith are reported for the first time on birds in Canada. After removal of an I. muris gravid female from a song sparrow, Melospiza melodia Wilson, at St. Andrews, New Brunswick, eggs were laid, which developed into larvae, and this new tick-host record demonstrates that birds have the potential to start a new tick population. We conclude that passerine birds disperse several species of ixodid ticks in Canada, and during spring migration translocate ticks from the United States, and Central and South America, some of which are infected with B. burgdorferi.

Animals↗
PubMed1999

Heterogeneity of viral IL-6 expression in HHV-8-associated diseases.

In order to characterize the expression of the viral interleukin-6 (vIL-6) homologue in various human herpesvirus 8 (HHV-8)-associated diseases, in situ hybridization and immunohistochemistry were applied to formalin-fixed specimens. These assays showed consistent expression of vIL-6 in primary effusion lymphomas and in a case of human immunodeficiency virus (HIV)-associated lymphadenopathy with a Castleman's disease-like appearance. In contrast, Kaposi's sarcoma specimens showed marked differences among specimens. In a consecutive series of specimens from the Johns Hopkins archives, vIL-6 expression was demonstrated in one of 13 cases. However, among 7 specimens selected from the AIDS Malignancy Bank because of their high levels of the T1.1 lytic transcript and virion production, vIL-6 expression was consistently demonstrated in infiltrating mononuclear cells and occasional spindle-shaped cells. Thus vIL-6 expression in clinical specimens correlates with other measures of the lytic viral cycle. Both assays generally give congruent results and are consistent with the possibility that vIL-6 expression plays a role in the pathogenesis of a variety of HHV-8-associated diseases.

Adult↗
PubMed1999

Disseminated histoplasmosis causing reversible gaze palsy and optic neuropathy.

Subacute disseminated histoplasmosis is an uncommon entity. Typical neuro-ophthalmologic manifestations are usually secondary to histoplasmomas or encephalitis. A 45-year-old man noted blurred vision while receiving empiric antituberculosis therapy for fever and diffuse granulomatous disease of unknown origin. Vertical-gaze palsy, right horizontal-gaze paresis, and mild right optic neuropathy were found on neuro-ophthalmologic examination. Further questioning revealed a history of frequent contact with fighting cocks from South America. Magnetic resonance images were consistent with multiple hemorrhagic infarcts, areas of inflammation, or both, and cerebral angiography showed changes consistent with vasculitis. A previously obtained biopsy specimen from the duodenum was restained and found to be positive for fungal elements. Serum antigen titers for Histoplasma capsulatum demonstrated evidence of active infection. This case is a rare example of a supranuclear ocular motility disturbance and optic neuropathy secondary to an occlusive vascular process in a patient with subacute disseminated histoplasmosis.

Diagnostic Errors↗
PubMed1999

Are there site-specific differences among extranodal aggressive B-cell neoplasms?

Aggressive B-cell lymphomas, including diffuse large cell, Burkitt, and lymphoblastic types, may affect a wide variety of extranodal sites. Up to 40% of these tumors are initially diagnosed in extranodal locations. Regardless of site, these tumors have many histologic similarities; however, some clinical, cytologic, immunologic, and etiologic features of these tumors seem to be distinctive for particular sites of extranodal presentation. In accordance primarily with the extranodal locations presented at the Society for Hematopathology Fourth Slide Workshop on Extranodal Hematopoietic/Lymphoid Disorders (Excluding Bone Marrow and Spleen), the distinctive features of the aggressive B-cell lymphomas of the mediastinum, breast, bone, skin, and body cavities as well as the rare, but primarily extranodal intravascular lymphomatosis, will be discussed.

Humans↗
PubMed1998

Epstein-Barr virus detection in nasopharyngeal tissues of patients with suspected nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV). Detection of EBV in biopsy specimens may serve as a tumor marker. METHODS: To assess the sensitivity and specificity of the polymerase chain reaction (PCR) and in situ hybridization in the diagnosis of NPC, formalin fixed, paraffin embedded nasopharyngeal biopsies from patients in Taiwan suspected of having NPC were studied. RESULTS: In specimens from 107 patients with NPC, EBV was detected by PCR in 97 cases (90.7%) and by EBER in situ hybridization in 105 cases (98.1%). In specimens from 61 patients without neoplasia, EBV was detected by PCR in 7 cases (11.5%) and by EBER in situ hybridization in 0 cases. CONCLUSIONS: These results suggest that although EBV DNA may occasionally be detected in nonneoplastic nasopharyngeal tissues, cells expressing EBER are not. EBER in situ hybridization may therefore prove to be a useful adjunct in the diagnosis of NPC.

Biopsy↗
PubMed1997

Blastic natural killer cell leukemia/lymphoma: a clinicopathologic study.

The classification of natural killer (NK)-cell and NK-like T-cell malignancies has undergone significant evolution in recent years. Although examples of NK-cell tumors resembling acute leukemia have been described anecdotally as blastic, blastoid, or monomorphic NK-cell leukemia/lymphoma (NKL/L), the clinical and pathologic features of these tumors have not been systematically defined. We report four patients with blastic NKL/L and describe the clinical, pathologic, and immunophenotypic findings in these cases. All patients were elderly (58-82 years) and presented with cutaneous plaques. Two patients also had adenopathy, and three patients had marrow involvement at presentation. Biopsy of cutaneous lesions showed atypical superficial and deep dermal lymphoid infiltrates. Involved lymph nodes were architecturally effaced by an interfollicular infiltrate with blastic cytologic features. In Wright-Giemsa-stained blood or marrow smears, tumor cells had finely distributed nuclear chromatin, many with nucleoli, and variable amounts of cytoplasm. In contrast to many NK and NK-like T-cell disorders, azurophilic cytoplasmic granules were absent or inconspicuous. The tumor cells were immunophenotypically distinctive. They expressed intermediate density CD45, as is characteristic of blasts; in addition, the cells were positive for HLA-DR, CD2, CD4, and the NK-associated antigen CD56. Surface CD3, cytoplasmic CD3, and CD5 were negative in all cases tested, whereas CD7 was expressed in two cases. In formalin-fixed tissue, tumor cells marked with antibodies to CD43, but not with other T- or B-lineage-related antibodies. All three cases studied for Epstein-Barr viral RNA by in situ hybridization were negative. Although treatments varied, all three patients with clinical follow-up died within months of the diagnosis. The clinical course in two patients culminated in an overtly leukemic phase. These findings suggest that blastic NKL/L represents a distinct clinicopathologic entity, characterized by cutaneous, nodal, and marrow involvement by blastic cells with immunophenotypic characteristics of true NK cells. The disease afflicts elderly patients, pursues an aggressive course, and may culminate in overt leukemia.

Aged↗
PubMed1997

Molecular detection of bone marrow involvement in intravascular lymphomatosis.

Intravascular lymphomatosis (IVL) is an extremely rare variant of aggressive non-Hodgkin's lymphoma characterized by confinement of neoplastic lymphocytes within vascular spaces. Although IVL is potentially curable with combination chemotherapy, diagnosis is often delayed, in part owing to the negative bone marrow biopsy specimens that are typical of this disorder. We hypothesized that use of a more sensitive method of analysis might identify small clonal B-cell populations in histologically negative bone marrow biopsy specimens from patients with IVL. With use of a recently described assay for immunoglobulin heavy chain gene rearrangement based on the polymerase chain reaction, we demonstrated clonal B-cell populations in histologically negative marrow specimens from five (100%) of five patients with IVL. None of these specimens demonstrated molecular evidence of the t(14;18) associated with follicular lymphoma, providing no evidence for a common derivation of IVL and follicular lymphoma. In summary, molecular analysis of routine bone marrow biopsy sepcimens from patients in whom the diagnosis of IVL is entertained may facilitate prompt recognition of a lympho-proliferative disorder and thereby permit timely therapeutic intervention. Moreover, these findings suggest that despite histologically negative staging bone marrow biopsy specimens, IVL typically disseminates early in its course, thus arguing against the use of localized therapy in this disorder.

Aged↗
PubMed1995

Localization of Epstein-Barr virus in Castleman's disease by in situ hybridization and immunohistochemistry.

Paraffin wax sections of lymph node biopsies from a total of thirteen patients with the morphologic and clinical features of Castleman's disease were analyzed for the presence of the Epstein-Barr virus (EBV) by in situ hybridization for the noncoding EBV early RNAs (EBERs) and by immunohistochemistry for the EBV-encoded latent membrane protein-1 (LMP-1). Of twelve cases of localized Castleman's disease EBER-positive cells were identified in five, and in these cases were only rarely found and were always confined to the interfollicular regions. LMP-1 was not detected in any of these cases, either alone or after dual staining for EBERs and LMP-1. (A similar pattern of EBER expression is seen in nonneoplastic lymphoid tissue from EBV-positive individuals.) No EBER-positive or LMP-1 positive cells were identified in a single case of multicentric Castleman's disease. In two additional patients initially diagnosed with Castleman's disease of localized plasma cell type, repeat biopsy showed Hodgkin's disease. In both cases Reed-Sternberg cells and their variants were identified in the original biopsy on which the diagnosis of Castleman's disease was made. In one of these cases these cells showed expression of EBERs and LMP-1, indicating latent infection with EBV. The results suggest that EBV is not generally associated with Castleman's disease. Further analysis of a series of cases of multicentric Castleman's disease is indicated.

Adult↗
PubMed1995

Epstein-Bar virus and progression of non-Hodgkin's lymphoma to Ki-1-positive, anaplastic large cell phenotype.

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of a variety of lymphoproliferative disorders (LPDs) including endemic Burkitt's lymphoma, Hodgkin's disease (HD), HIV-associated non-Hodgkin's lymphomas (NHLs), and LPDs arising in immunosuppressed transplant patients. More recently, EBV has been associated with Ki-1-positive anaplastic large cell lymphoma (ALCL), a recently described NHL that shares with HD expression of the CD30 antigen Ki-1. Because EBV has been shown to induce Ki-1 expression in vitro, and ALCL has been diagnosed in patients with prior or concurrent HD or NHL, it has been proposed that EBV may mediate progression of a "primary" lymphoma to a "secondary" ALCL. We report a case in which an AIDS-associated, Ki-1-negative, large-cell immunoblastic lymphoma progressed to a Ki-1 positive ALCL. Analysis of the immunoglobulin heavy chain locus revealed a clonal relationship between these morphologically and immunophenotypically distinct tumors. Although EBV was absent from the original large-cell immunoblastic lymphoma as assessed by in situ hybridization for EBV-encoded small RNA1 (EBER1), polymerase chain reaction for EBNA-1, immunocytochemistry for latent membrane protein 1, and Southern blot hybridization for EBV terminal repeat sequences, all for techniques confirmed the presence of EBV in the secondary ALCL. Moreover, analysis of EBV terminal repeat sequences indicated that the ALCL resulted from expansion of a single EBV-infected clone. These data suggest that EBV may mediate progression of NHL to Ki-1-positive ALCL, and that in some instances, EBV may be involved in the later stages of clonal progression of NHL.

AIDS-Related Opportunistic Infections↗
PubMed1994

Epstein-Barr-encoded RNA in situ hybridization: diagnostic applications.

Latent Epstein-Barr virus (EBV) infection is associated with a variety of malignancies and other diseases. Highly restricted viral antigen expression and low viral genome copy number in infected tissues impede conventional immunohistochemical or in situ hybridization approaches to the detection of virus in these tissues. In situ hybridization detection of two small but very abundant nuclear RNAs known as the EBERs serves as an alternative approach. The EBERs are stable over time and can be detected in all common fixatives. This technique facilitates characterization of the cellular locus of latent EBV infection in histologically complex tissues, such as Hodgkin's disease and angioimmunoblastic lymphadenopathy with dysproteinemia.

Herpesviridae Infections↗
PubMed1994

Epstein-Barr virus is infrequently identified in non-Hodgkin's lymphomas associated with Hodgkin's disease.

Epstein-Barr virus (EBV) was identified in a subset of cases of Hodgkin's disease (HD) and in some non-Hodgkin's lymphomas (NHLs), particularly those associated with immunodeficiency. Because patients with HD have associated immune system defects, we hypothesized that EBV might be involved in NHLs associated with HD. Using fixed paraffin sections and in situ hybridization for EBV EBER1 RNA, we studied 12 cases of composite NHL + HD, two patients with NHL who simultaneously also had HD involving a different site (simultaneous HD and NHL), 14 NHLs arising in patients who previously had HD, and seven NHLs from patients who subsequently developed HD. Epstein-Barr virus was identified most frequently in composite NHL + HD. Five (42%) cases of composite NHL + HD contained EBV in Reed-Sternberg and Hodgkin cells, four of which also had EBV-positive NHLs, diffuse mixed or large-cell type, with 10 to more than 50 EBV-positive cells per x400 microscopic field. These results suggest that in this subset of four cases, both the NHL and HD components may have arisen from the same EBV-infected progenitor cell. We did not find EBV in two cases of simultaneous NHL and HD or in seven NHLs preceding development of HD. We identified EBV in only two of 14 NHLs following HD, one small noncleaved cell lymphoma and one plasmacytoma, both containing more than 50 EBV-positive cells per x400 microscopic field. These results suggest that EBV plays a minimal role in NHLs associated with HD, with the exception of composite NHL + HD. Hodgkin's disease-associated immune defects may be involved in the pathogenesis of a subset of NHLs following HD, but the exact pathogenesis of most NHLs associated with HD remains uncertain. Parallels with the high-grade Burkitt-like lymphomas associated with human immunodeficiency virus infection are noted.

Adult↗
PubMed1994

Intravascular lymphomatosis: a clinicopathologic study of 10 cases and assessment of response to chemotherapy.

PURPOSE: We report a clinicopathologic study of 10 cases of intravascular lymphomatosis (IVL) seen at a single institution, and assess the response to chemotherapy in these patients, as well as those collected from a literature review. PATIENTS AND METHODS: The clinical, pathologic, and immunophenotypic features of 10 cases of IVL diagnosed at the Johns Hopkins Hospital since 1977 were studied. Follow-up information was obtained in each case by consultation with the treating physician. In addition, cases of IVL reported previously in which patients were treated with chemotherapy and for which follow-up data were available at the time of publication were reviewed. RESULTS: In the present series of 10 cases, the most common clinical features were fever of unknown origin (FUO), mental status changes, and rash. Diagnostic specimens were obtained from a variety of sources, including brain, skin, prostate, liver, kidney, and gallbladder. All of the four patients treated with combination chemotherapy are alive and two have achieved long-term survival (48 and 45 months, respectively); the remaining two are alive and in complete remission (CR) after short follow-up duration of 6 months. Among 35 patients reported in the literature who received chemotherapy (including four from this series), 43% attained a CR and were free of disease at the time of publication. None of the three patients in our series who received localized therapy (surgery with or without radiation therapy) is alive (mean survival duration, 9 months). For the three patients diagnosed at postmortem examination, the mean interval between onset of symptoms and death was 3 months, and disease was widespread. CONCLUSION: These findings suggest that IVL represents a high-grade non-Hodgkin's lymphoma (NHL) with a propensity for systemic dissemination, and that CR and long-term survival may result in patients treated with aggressive combination chemotherapy.

Aged↗
PubMed1994

Long-term follow-up of a CHOP-based regimen with maintenance therapy and central nervous system prophylaxis in lymphoblastic non-Hodgkin's lymphoma.

The Eastern Cooperative Oncology Group (ECOG) conducted a phase II trial in adult patients with lymphoblastic non-Hodgkin's lymphoma. Thirty-nine patients with no central nervous system (CNS) involvement were treated with an induction cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)/L-asparaginase regimen and CNS prophylaxis that included intrathecally administered methotrexate given 6 times and 24 Gy midplane cranial radiation in 12 fractions. Thirty-one patients (79%) achieved a complete remission (CR). Of the 31 patients with CRs, 12 relapsed (39%). CNS relapse occurred in three patients. All patients who entered a CR were treated with maintenance CHOP, cytosine arabinoside (AraC), and methotrexate and subsequently with Ara-C and methotrexate. Life-threatening leukopenia or thrombocytopenia was experienced in 69% of patients in the induction phase and in 70% in the maintenance phase. Nineteen of 39 patients (49%) remain in CR with a followup to 9 years. Bone marrow involvement was associated with a significantly worse survival (P = 0.03).

Adolescent↗