AIDS and the anaesthetist.
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Biomedical subjects
Publications and source records attributed to R K Brynes.
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This report describes the experience of the Southeastern Cancer Study Group (SECSG) with the frozen-section immunoperoxidase phenotyping of 162 cases of B-lineage non-Hodgkin's lymphomas. The authors used a panel of 13 different markers with varying degrees of specificity for B lymphocytes and B-cell neoplasms. All lymphomas were classified according to the International Working Formulation. Several antibodies, including anti-immunoglobulin, B1, Leu 12, and Leu 14 were B-cell-specific markers that were generally pan-reactive. Several other monoclonal antibodies, however, were selectively reactive with subpopulations of B-cell lymphomas. Three "selective-B" antigens (BA1, p24, CALLA) were found on about half of the B-cell lymphomas tested, while another three (HB31, transferrin receptor, C3d receptor) were found on about two-thirds of the lymphomas tested. Leu 1 reacted with 18% of the B-cell lymphomas, particularly the small lymphocytic lymphomas. When the reactivity of the monoclonal antibodies was compared with the histologic classification, two important points became apparent. First, with the large panel of antibodies, there was tremendous phenotypic diversity even among histologically similar tumors. Second, however, not all possible combinations of antibody phenotypes were encountered. That is, clusters of antigenic phenotypes were seen, and these phenotypes correlated to some degree with the histologic diagnosis of the tumor. Small lymphocytic and follicular lymphomas tended to be phenotypically distinct, although there was some overlap. Intermediate- and high-grade lymphomas were phenotypically more diverse. The more common phenotypes of lymphomas encountered could not be reconciled with any simple linear scheme of neoplastic B-cell differentiation.
Lymph nodes of patients symptomatically infected with the acquired immunodeficiency syndrome (AIDS) virus show a spectrum of morphologic changes ranging from marked lymphoid hyperplasia to marked lymphocytic depletion. These changes can be grouped into three distinct patterns. The type I pattern features follicular and paracortical hyperplasia, and is associated with chronic lymphadenopathy. The type II pattern, which shows diffuse lymphoid hyperplasia but loss of germinal centers, signifies evolution of chronic lymphadenopathy to AIDS. The type III pattern shows marked lymphocytic depletion and represents the end-stage lymph node seen in fatal AIDS. These histologic patterns are closely correlated with the clinical and immunologic status of patients infected with the AIDS virus.
Frozen sections of lymph nodes from 20 homosexual men with chronic generalized lymphadenopathy and of lymph nodes showing follicular hyperplasia from 14 patients without known risk factors of the acquired immunodeficiency syndrome were studied with monoclonal antibodies to T-cell subsets and to the HLA-DR antigen. In T-cell areas of the lymph nodes, excluding tertiary paracortical nodules, the mean T-helper-to-T-suppressor ratio (Th/Ts) +/- 1 SEM was significantly lower in the homosexual group (1.07 +/- 0.06) when compared with the control group (2.49 +/- 0.23), P less than .0001. In seven homosexual men, cell suspensions from the same lymph nodes were analyzed using a fluorescence-activated cell sorter. Results obtained by this method and by immunohistochemistry were comparable except in a homosexual man whose lymph node contained large tertiary paracortical nodules. Although the Th/Ts ratios of the blood and lymph nodes of the same patients were both low, there was not good correlation between the two sets of values (r = .2). Furthermore, there was not good correlation between blood lymphocyte count and lymph node Th/Ts ratios (r = .45). The lymph node Th/Ts ratios of the homosexual patients show less variations compared with the control group. The patient who subsequently developed multiple opportunistic infections had the lowest value. Whether the lymph node Th/Ts ratio has prognostic significance in patients with the lymphadenopathy syndrome warrants further investigation.
A 47-year-old woman developed a unique myeloproliferative disorder 36 months after receiving adjuvant chemotherapy postoperatively for breast carcinoma. Her bone marrow and peripheral blood exhibited many of the myelodysplastic changes commonly observed in treatment-linked leukemia. In addition, there was striking marrow and blood eosinophilia and eosinophilic infiltration in multiple organs. She also developed a poorly differentiated lymphocytic lymphoma which responded to therapy. Her myeloproliferative disorder, with marked eosinophilia, continued to progress, however, and she died shortly after its diagnosis.
Four thymomas, two from patients with myasthenia gravis, were studied using a panel of monoclonal antibodies. Almost all the associated lymphocytes were T-cells with the common thymic lymphocyte phenotype, suggesting that the neoplastic epithelium can provide a microenvironment that retains or perhaps attracts immature T-cells. HLA-Dr antigens were expressed by some of the epithelial cells and many of the lymphoid cells in the perivascular space. The Leu-7 antigen was present on a subset of epithelial cells and had a highly variable expression in different thymomas. The percentage of lymphocytes bearing the OKT8-defined antigen appeared to be lower in patients with myasthenia gravis, while the expression of other markers did not appear to be consistently or significantly different. There did not appear to be marked differences in the lymphocyte subpopulations of thymomas with different morphology, and there was no evidence of differentiation of the thymomas into cortical and medullary areas.
We report four patients with expansion of a unique population of lymphocytes that is consistently associated with neutropenia. Two patients also had rheumatoid arthritis and autoantibodies. The lymphocytes contained many cytoplasmic azurophilic granules, which possessed strong acid phosphatase activity. Multiple cytoplasmic parallel tubular arrays were observed ultrastructurally. These granular lymphocytes showed the T suppressor/cytotoxic cell phenotype (E+, OKT3+, OKT8+, OKT4-, OKM1-, OKI1-) and exhibited antibody-dependent cell-mediated cytotoxic activity but little or no natural killer cytotoxicity. They did not respond to recall antigens, concanavalin A, or pokeweed mitogen, but the cells from one patient did respond to phytohemagglutinin. No in vitro suppressor cell activity on mitogenic responses of allogeneic cells and on mixed lymphocyte cultures could be demonstrated. There was no evidence of suppression of immunoglobulin synthesis in vivo. It is uncertain that the expansion of this subset of lymphocytes represents a leukemic process. Their constant association with neutropenia, however, raises the possibility that the increase in large granular lymphocytes and neutropenia might be pathogenetically related.
This report describes the experience of the Southeastern Cancer Study Group (SECSG) with a transport medium used for immunologic phenotyping of non-Hodgkin's lymphomas. In a 2-mo pilot study, portions of 53 specimens of non-Hodgkin's lymphoma from four member institutions of the SECSG and affiliated community hospitals were sent by regular mail to a central laboratory. Immunologic phenotyping was carried out using a frozen section immunoperoxidase technique. In 48 of the cases, a clear-cut immunologic phenotype was obtained. Thirty-four tumors were of B cell origin and 7 had T cell markers. Six of the remaining lymphomas had neither B nor T cell markers, and the seventh had both. In 12 cases, phenotyping was also carried out at the originating institution using conventional cell suspension techniques; agreement between the two methods was excellent. The immunologic results were correlated with histopathologic diagnosis standardized using the Working Formulation for non-Hodgkin's lymphomas. It was found that the low grade tumors were all B cell, but that the intermediate grade tumors were very heterogeneous immunologically. About one-fourth of the diffuse, intermediate grade or miscellaneous tumors had T cell markers. Our results indicate that immunologic phenotyping may be performed satisfactorily on transported material, making multiinstitution studies on the prognostic significance of immunologic phenotype in non-Hodgkin's lymphomas feasible.
The acquired immune deficiency syndrome (AIDS) manifested by severe opportunistic infections, Kaposi's sarcoma, or lymphoma often has a prodrome of lymphadenopathy accompanied by constitutional symptoms. We studied the histopathologic findings of lymph node biopsy specimens and peripheral blood immunologic parameters of 24 clinically indistinguishable homosexual men with chronic generalized lymphadenopathy. Two different morphological patterns were observed: (1) lymph nodes with follicular and paracortical hyperplasia in 21 patients who had had no clinical deterioration and (2) an atypical pattern of lymphoid proliferation in three patients who experienced rapid development of non-Hodgkin's lymphoma and/or opportunistic infections. Several immunologic laboratory results paralleled these changes. Lymph node morphological findings seem to be a useful predictor of outcome in homosexual men with generalized lymphadenopathy.
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Two patients with inflammatory meningeal masses were studied. Lesions in both patients showed varying proportions of meningothelial and inflammatory components. The non-neoplastic nature of the inflammation was confirmed in one case by lymphocyte surface marker study, which showed T and B cells in one to four ratio, and by immunohistochemistry, which revealed polyclonal plasma cells. The abundant histiocytes contained muramidase and often enclosed intact lymphocytes or plasma cells within their cytoplasm, i.e., emperipolesis. Their surfaces bore slender interdigitating pseudopodia, intercellular junctions, and subplasmalemmal linear densities. The derivation of these histiocytes is uncertain: mononuclear phagocytes, meningothelial cells, and multipotential meningeal cells are all possible progenitors. A comparison with eleven similar reported cases reveals a tendency for inflammatory meningeal masses to occur in the young, as well as a predilection for posterior fossa involvement. They resemble the extranodal lesions of sinus histiocytosis with massive lymphadenopathy, as well as plasma cell granulomas or inflammatory pseudotumors of lung and other tissues. However, it is possible that these lesions represent a variant of meningioma in which an unusual immunological response has been evoked.
Part of the cytotoxic action of alkyl-lysophospholipids (ALP) on leukemic cells is known to result from the lack of an O-alkyl cleavage enzyme and its antimetabolic effect which results in a toxic lysophospholipid buildup. Further, ALP (5 micrograms/ml) suppresses clonogenicity and tritiated thymidine uptake in HL60 cultures after 24 hr of exposure. The effect of ALP on two leukemic cell lines, HL60 and K562, measured by two nuclear magnetic resonance (NMR) techniques and examined by electron microscopy is reported. 31P-NMR spectroscopy indicates that the adenosine 5'-triphosphate:adenosine 5'-diphosphate ratios are unaffected after 24 hr, as is mitochondrial morphology, judging by electron micrographs. However, cell membrane integrity in HL60 is altered at that time. The earliest ALP effects occur in NMR internal water relaxation at 1 hr after ALP exposure, followed by a small reduction in tritiated thymidine uptake at 4 hr. No effect is observed in K562 cell cultures in morphology or NMR measurements. No new 31P-labeled metabolites were detected in either cell line as a result of drug treatment.
Morphologic patterns in regional lymph nodes draining resected tumors correlate with in vitro immunologic data and have been reported to predict survival, stage of disease, and presence or absence of metastases. The strength of the relationship between immunomorphologic findings and survival rates varies with the type of tumor, perhaps because of relative immunogenicity, tumor size and growth rate, or even the stimulation of the lymph nodes by infection. Nevertheless, there is remarkable agreement among investigators on key observations, which yield more prognostic information than can be obtained by standard methods.
Two girls, each less than 2 yr of age, developed acute megakaryoblastic leukemia (malignant myelosclerosis). Both presented with anemia, severe thrombocytopenia, and a low percentage of blasts in their peripheral blood. Their marrow showed marked reticulin fibrosis with an increase in blasts and immature megakaryocytes. The blasts stained negatively for myeloperoxidase and Sudan Black B, but showed acid phosphatase (ACP) and alpha-naphthyl acetate esterase (ANAE) activity inhibitable by sodium fluoride. They were identified as megakaryoblasts by the platelet peroxidase reaction. Cytogenetic studies showed multiple chromosomal abnormalities in both cases. Chemotherapy with vincristine, prednisone, and L-asparaginase was without effect, while daunorubicin and cytosine arabinoside induced a complete remission in one case. The second case responded to a combination of cytosine arabinoside, daunorubicin, and 6-thioguanine. This article documents that acute megakaryoblastic leukemia occurs in early childhood and describes its clinical, pathologic, and cytogenetic features. Previous reports of childhood "myelofibrosis" are reviewed, and their possible relationship with acute megakaryoblastic leukemia is discussed.
A case of prolymphocytic leukemia was studied by using light and electron microscopy, cytochemistry and multiple immunological markers for T and B lymphocytes. Cytochemical and immunological studies showed that the cells were T-lymphocytes. By using monoclonal antibodies to human T-cell subsets, we found that these cells had the T-helper cell phenotype. The usefulness of multiparameter studies in subclassifying T-cell malignancies is discussed and the literature on T-prolymphocytic leukemia reviewed.
Giant lymph node hyperplasia (GLNH) is generally thought to represent a benign process. A patient with GLNH of the chest wall had part of the lymph node replaced by large nodules of infiltrating plasma cells, and a serum paraprotein of the IgG lambda type. A peroxidase-antiperoxidase immunocytochemical technic showed that the plasma cells within areas of typical appearing GLNH were polyclonal, whereas those making up the nodular infiltrates were monoclonal. The observation of a plasmacytoma arising in this lesion demonstrates the neoplastic potential of GLNH.
Sinus histiocytosis with massive lymphadenopathy is a benign pseudolymphomatous disease with distinctive microscopic features. Painless cervical adenopathy is the most characteristic clinical finding, although other node groups and extranodal sites may be involved. Of 200 patients in a case registry, 8 had neurologic symptoms. The lesions included vertebral canal and intracranial infiltrates and a destructive vertebral body lesion. Two patients had both cord compression and intracranial disease; one of them died after 10 years of disease. Seven patients were alive 1 to 15 years after disease onset.
Between August, 1978, and March, 1981, 24 boys with acute lymphocytic leukaemia (ALL) (14 non-B-cell non-T-cell, 6 pre-B-cell, and 4 T-cell) underwent bilateral wedge testicular biopsy at initial diagnosis. All testes were of normal size. Histological analysis was performed independently by three pathologists, 4 (3 non-B non-T, and 1 pre-B) of 20 patients with non-T-cell ALL demonstrated testicular focal lymphoblastic involvement. Successful induction chemotherapy without concomitant testicular irradiation completely eradicated testicular infiltrates in all 4 patients. Only 1 of the 4 T-cell patients had pre-treatment testicular infiltrates. Unlike boys with non-B non-T leukaemia, attainment of bone-marrow remission in this patient was associated with persistent testicular disease. These preliminary data indicate that in patients with ALL of non-T-cell type, systemic induction chemotherapy eradicates the small testicular infiltrates of lymphoblasts. Prophylactic testicular irradiation in this group of patients does not seem to be warranted.