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L W Diamond

Publications and source records attributed to L W Diamond.

36 records · Page 2Linked to original sources

Clinical manifestations of intrathoracic cutaneous T-cell lymphoma.

Intrathoracic involvement with cutaneous T-cell lymphoma (CTCL) was documented in eight patients with mycosis fungoides and two patients with Sĕzary syndrome. The radiographic findings consisted of multiple bilateral parenchymal nodular densities (five patients), patchy areas of consolidation (two patients), diffuse reticulonodular or interstitial infiltration (two patients), and pleural effusion without underlying parenchymal disease (one patient). Dyspnea on exertion and nonproductive cough were the most frequent presenting symptoms, and physical examination of the lungs was usually normal. In one patient a partial Pancoast's syndrome developed from a pulmonary apical mass. Results of blood gas studies and pulmonary function tests indicated an alveolar-capillary block in gas diffusion. Although the antemortem diagnosis was often suggested on cytopathologic preparations or on tissue obtained by transbronchial or percutaneous needle aspiration biopsy, a definitive diagnosis of CTCL usually required an open-lung biopsy. The response of pulmonary infiltrates to various systemic chemotherapeutic agents was variable, and the mean survival after initiation of drug therapy was 9.5 months. The findings suggest that combined modality therapy should be considered for patients with extracutaneous CTCL.

Aged↗

A flow cytometric assay of neutrophil degranulation.

A quantitative assay of neutrophil degranulation was developed using flow cytometry. Dog neutrophils were purified to greater than 95% purity and viability by isopyknic density centrifugation in an isosmotic medium. These cells concentrated the fluorochrome acridine orange (AO) in their azurophilic granules, but not in specific granules. Also contained in the azurophilic granules are elastase, myeloperoxidase, and approximately 50% of the lysozyme activity. The fluorochrome was released concomitantly with elastase activity, as shown by flow cytometry, fluorescence microscopy, and biochemical assay in response to the ionophore A23187. By flow cytometry, unstimulated cells are distributed in a single broad peak of high fluorescence intensity. With increasing concentrations of A23187 (0.48-4.80 microM), a greater proportion of the cells shifted to a single peak of low fluorescence intensity. Few cells with intermediate fluorescence were observed. These analyses revealed that the neutrophils degranulated in a quantal, all-or-none response.

Acridine Orange↗

Flow cytometry in the diagnosis and classification of malignant lymphoma and leukemia.

DNA content and light scatter were measured by flow cytometry (FCM) in 103 patients including 43 patients with non-Hodgkin's lymphoma (NHL), eight patients with Hodgkin's disease (HD), 17 patients with acute lymphoblastic leukemia (ALL), ten patients with acute nonlymphocytic leukemia (ANLL), and 25 patients with chronic lymphoid leukemias. Controls consisted of 42 nonneoplastic specimens obtained from lymph nodes, spleen, bone marrow, and peripheral blood. Each specimen was analyzed after staining with a hypotonic solution of propidium iodide using nuclei isolated from chicken erythrocytes as an internal standard. The DNA content and light scatter of the human populations was expressed as a ratio between the DNA content (or light scatter) of the human G0--G1 cells and that of the chicken erythrocytes nuclei. The mean DNA ratio for the 42 nonneoplastic samples was 2.58 +/- 0.045 (SD). In these samples the DNA coefficient of variation of the human G0--G1 peak ranged from 1.48--3.28% (mean, 2.33 +/- 0.54%). The FCM data in the NHL was compared to morphologic diagnoses made according to the "working formulation of NHL for clinical usage" recently proposed by a panel of international experts. Eight of 17 (47%) low grade NHL, one of two (50%) mycosis fungoides, ten of 14 (71%) intermediate grade NHL, nine of ten (90%) high grade NHL, nine of 17 (53%) ALL, three of ten (30%) ANLL, and seven of 25 (28%) chronic lymphoid leukemias had abnormal DNA ratios indicative of aneuploidy. In addition, several cases had normal DNA ratios but G0--G1 coefficients of variation outside of the normal range. All cases of HD had normal DNA values except one case with a small percentage of near tetraploid cells. The mean percentage of cells with S-phase DNA content for the low grade NHL (2.2 +/- 0.8%) was significantly lower than that of the intermediate grade NHL (12.1 +/- 4.9%; P less than 0.0001). The mean S-phase value for the intermediate grade NHL was significantly lower than that of the high grade NHL (22.6 +/- 11.1%; P less than 0.001). The three prognostic categories of NHL designated by the new formulation were clearly distinguishable by the FCM data. Light scatter was not particularly useful for distinguishing nonneoplastic from neoplastic populations. The mean light scatter coefficient of variation of the ALL (15.2%) was significantly lower than that of ANLL (20.5%), however (P less than 0.04).

Bone Marrow↗

Lymphoblastic lymphoma: a clinicopathologic study of 95 patients.

A retrospective clinicopathologic study of lymphoblastic lymphoma was based on 95 patients from the files of the Repository Center for Lymphoma Clinical Studies. All patients were treated according to different protocols of Cooperative Oncology groups sponsored by the National Cancer Institute. The patients ranged in age from 4 to 84 years, with a median of 30 years. Sixty-eight patients were male and 27 female, with respective median ages of 27 and 50 years. The male-to-female ratio was 2.5:1. Forty patients had mediastinal masses; 30 (75%) of whom were male. The median survival of all patients was 17 months (range 1-100 months). To ascertain the influence of various clinical and morphologic parameters of survival, univariate and multivariate statistical analyses were performed. Patients older than 30 years of age had significantly lower incidences of mediastinal involvement (P = 0.01), number of mitotic figures (P = 0.04), and development of leukemia (P = 0.02) than patients younger than 30. Whereas lymphoblastic lymphoma is generally considered to be a disease of children and young adults, this study indicates that lymphoblastic lymphoma occurs in all age groups. These findings further suggest that lymphoblastic lymphoma may have a different biologic behavior in older patients.

Adolescent↗

Morphologic criteria for the differentiation of follicular lymphoma from florid reactive follicular hyperplasia: a study of 80 cases.

A study was made of 80 patients whose lymph nodes were characterized by the presence of follicles throughout the lymph node. The patients were divided into two groups on the basis of the clinical follow-up information. The first group consisted of 20 patients who were alive and disease-free at the end of five years without therapy. The patients in this group were classified as having florid reactive follicular hyperplasia (FRFH). The second group of 60 patients had progressive, recurrent, clinically active disease and were classified as having follicular lymphoma (FL). Forty-six were dead of active disease, and 14 were alive with disease. Various morphologic parameters were evaluated at low and high magnification, and statistical comparisons were made between FRFH and FL. Although several criteria were helpful in distinguishing FRFH from FL, the single most valuable criterion was the type of pattern encountered. Follicles of variable size and shape lying adjacent to each other throughout the lymph node without or with very little intervening tissue are diagnostic of FL. This pattern was evident in 85% of the FL cases, but was not observed in any of the cases of FRFH.

Adolescent↗

Malignant lymphoma, intermediate lymphocytic type: a clinicopathologic study of 42 cases.

A clinicopathologic analysis of 42 cases of non-Hodgkin's lymphoma of the intermediate lymphocytic type (ILL) having morphologic features between those of well-differentiated (WDLL) and poorly differentiated lymphocytic lymphoma (PDLL) is presented. In lymph node sections, ILL was characterized by a diffuse proliferation consisting predominantly of small lymphoid cells with slightly irregular or indented nuclei. A mixture of lymphoid cells with entirely round nuclei and lymphoid cells with angulated and cleaved nuclei was also present, but each of these two cell populations did not comprise more than 30% of the total. The median age of the patients was 65 years, and the male-to-female ratio was 5:1. Generalized lymphadenopathy was evident in 74% of the patients, and B symptoms were presented in 36%. Peripheral blood involvement was present at the onset of disease in 21% of the patients, and the bone marrow was involved by lymphoma in 76% of those examined. Five percent of the patients had Stage I disease, 24% had Stage III disease, and 71% had Stage IV disease. Ninety-three percent of the patients received multiagent chemotherapy and 41% achieved a complete remission. The overall median survival was 31 months. Clinical features which appeared to influence survival adversely included the presence of B symptoms (P = 0.007), age greater than 70 years (P = 0.09), an absolute lymphocyte count above 5000/mm3 (P = 0.05), and anemia (P = 0.09). Achievement of a complete remission influenced survival favorably (P = 0.02). Pathologic features which appeared to influence survival included sinus obliteration, which had an adverse effect (P = 0.05), and the presence of residual germinal centers which had a favorable effect (P = 0.06). Patients with 0-5 mitoses/10 high power fields (HPF) had a significantly longer survival than those with more than 20 mitoses/10 HPF (P = 0.02), while those with 6-20 mitoses/10 HPF had an intermediate survival. The clinical and pathological features of patients with ILL suggest that this entity is closely related to PDLL and should be distinguished from WDLL.

Adult↗

The relationship between lymphocyte nuclear morphology and cell cycle stage in lymphoid neoplasia.

A significant percentage of lymphoid cells isolated from three lymphoid neoplasms (nodular lymphoma mixed cell type, mycosis fungoides, and Sézary syndrome) had tetraploid or near-tetraploid DNA content, as determined by flow cytometric analysis. In each case, a morphologically distinct population of cells with large, irregular nuclei was present, the percentage of which corresponded to the percentage of tetraploid cells. In a fourth case (diffuse "histiocytic" lymphoma), cells were sorted on the basis of DNA content from the G0-G1 compartment and compared morphologically to cells sorted from the S-G2(M) compartment. The G0-G1 cells has clumped nuclear chromatin, lacked prominent nucleoli, and had a mean nuclear diameter of 10.18 +/- 1.22 micrometer. The sorted cells with S-G2 (M) DNA content had one to several prominent nucleoli and less clumped nuclear chromatin, and they were significantly larger, with a mean nuclear diameter of 13.76 +/- 1.59 micrometer (p less than 0.00001). These preliminary results suggest that, in lymphoid malignancies, certain morphologic characteristics of individual lymphoid cells are related to their DNA content (level of ploidy) and/or the stage of the cell within its division cycle.

Cell Cycle↗

Terminal deoxynucleotidyl transferase activity in neoplastic and nonneoplastic hematopoietic cells.

Terminal deoxynucleotidyl transferase activity was investigated by enzyme assay and (or) an indirect immunofluorescence method with specimens from 151 patients who had a variety of neoplastic and nonneoplastic conditions: leukemia, 62; non-Hodgkin's lymphoma, 36; Hodgkin's disease, seven; lymph nodes without neoplasms, 21; normal peripheral blood, 15; normal bone marrow, ten. Immunologic studies were done on samples from 82 of these patients. Increased terminal deoxynucleotidyl transferase activity was found by both methods in patients who had acute lymphoblastic leukemia and the lymphoid blast crisis of chronic myelocytic leukemia and by the immunofluorescence method in patients who had lymphoblastic lymphoma. A single patient with acute monoblastic leukemia was found by both technics to have increased enzyme activity. Three B-cell proliferations were positive by the enzyme assay; none was positive with the immunofluorescence method. In the remaining 42 B-cell proliferations, the levels of terminal deoxynucleotidyl transferase activity were found to be normal by both the enzyme assay and the immunofluorescence method. Cytoplasmic positivity was observed in as much as 10% of the cells in 13 specimens that were otherwise negative and in eight samples in association with nuclear positivity. A comparison of terminal deoxynucleotidyl transferase activity in microunits/mg protein (enzyme assay) with the percentage of positive cells (immunofluorescence method) yielded a correlation coefficient of 0.62 (P less than 0.01).

Adult↗

Immunological markers and DNA content in a case of giant lymph node hyperplasia (Castleman's disease).

Little is known about the immunologic characteristics of the cells in giant lymph node hyperplasia (GLNH). For this reason, cell surface markers and intracytoplasmic immunoglobulins were determined on a case of GLNH. In addition, cellular DNA content was determined by flow analysis. A 59-year-old male underwent thoracotomy for a posterior madiastinal mass, which was entirely excised. Histologically, the mass was diagnosed as GLNH with features of both the hyaline-vascular and plasma-cell types. Preoperatively, the patient had a broad-based hypergammaglobulinemia with an increase in serum IgG. Two months postoperatively, the serum protein electrophoresis had returned to normal. Surface immunoglobulins (SIg) were determined on fresh cells in suspension using a polyvalent antiserum and monospecific antisera against heavy and light chains. Ten percent of the cells had SIg. The distribution of SIg-bearing cells was polyclonal. Intracytoplasmic immunoglobulin (CIg), as determined by immunofluorescence on ethanol-fixed smears from the cell suspensions, showed 6% positive cells. The distribution of cytoplasmic immunoglobulin was similarly polyclonal. Ethanol-fixed frozen sections also showed a polyclonal pattern when stained for CIg. Fifty-two percent of fresh cells in suspension formed Erosettes. These immunologic characteristics do not differ from those observed in non-neoplastic lymphoid tissues. A DNA content histogram was obtained by flow microfluorometry using ethanol-fixed cells stained with propidium iodide following RNase treatment. The DNA content distribution was within the normal limits established by the study of non-neoplastic lymphoid tissues.

Cytoplasm↗

Prolymphocytic leukemia: flow microfluorometric, immunologic, and cytogenetic observations.

Cells isolated from four patients with prolymphocytic leukemia were evaluated by surface markers, cytogenetics, and flow microfluorometric analysis of cell size and DNA content. All four patients had B-cell markers with a high density of IgM, kappa type, and Ia-like antigen. Less intense staining for surface IgD was also observed. In each patient studied, chromosomal modes were in the hypodiploid or near-diploid range. Despite the karyotypic abnormalities, the cellular DNA content, as determined by flow microfluorometry, was within the normal limits in all cases. This suggests that the variability in chromosome numbers seen in these patients may reflect an abnormality in DNA package rather than differences in total DNA content. The modal electronic cell size of the prolymphocytes, determined by light scatter, was readily distinguishable from that of normal peripheral blood lymphocytes and the lymphocytes of chronic lymphocytic leukemia. Fewer than 4% of the peripheral prolymphocytes had S-phase DNA content, a finding consistent with the chronic nature of this leukemia.

Chromosomes, Human↗

Percentage of cells in the S phase of the cell cycle in human lymphoma determined by flow cytometry.

The percentage of cells with S phase DNA content (S cells) was determined by flow cytometry in cell suspensions obtained from 27 patients with non-Hodgkin's lymphomas. DNA was measured in ethanol-fixed cells stained with propidium iodide after RNase treatment. Cells from 17 samples were also exposed to [3H]-thymidine and labeling indices were determined. An excellent linear correlation was observed between the percentage of S cells calculated by flow cytometry and the labeling index (r = 0.95). To determine the relationship between the percentage of S cells and the clinical behavior of the tumors, the survival of the 27 patients was analyzed. None of the patients was undergoing antineoplastic therapy at the time of the study. The patients were separated into 2 groups according to the percentage of S cells calculated by flow cytometry: those with less than 5% S cells and those with higher than 5% S cells. Clinical follow-up ranged from 5 to 20 months. While 7 of 12 patients with tumors containing more than 5% S cells have died of lymphoma (median survival, 9 months), there has been only one death from lymphoma among 15 patients with tumors containing less than 5% S cells. The difference in survival between these two groups is statistically significant (P = 0.01).

Autoradiography↗

Flow analysis of DNA content and cell size in non-Hodgkin's lymphoma.

Cellular DNA content, Coulter volume, and light scatter were measured in cell suspensions from 30 non-Hodgkin's lymphomas in order to assess flow analysis as a quantitative and reproducible means of evaluating these diseases. Nonneoplastic control populations included 31 samples obtained from lymph nodes, spleens, tonsils, and peripheral blood. Cellular DNA and light scatter were measured on ethanol-fixed cells by flow microfluorometry using nuclei isolated from chicken erythrocytes as an internal standard. For DNA analysis, the cells were stained with propidium iodide following RNase treatment. The cellular DNA content of the human populations was expressed as a ratio between the DNA content of the human G0-G1 cells and that of the chicken erythrocyte nuclei. The mean DNA ratio for the 31 nonneoplastic samples was 2.83 +/- 0.08 (S.D.) In these samples, the coefficient of variation of the human G0-G1 peak ranged from 2.27 to 3.63% (mean 3.09 +/- 0.32%). Fifteen of 30 non-Hodgkin's lymphomas, including 7 of 15 low-grade lymphomas and 8 of 15 high-grade lymphomas, had abnormal DNA content, the majority containing hyperdiploid G0-G1 populations. In six malignant lymphomas with normal DNA content, the coefficient of variation of the human G0-G1 peak, corrected for differences in instrument setting was greater than that seen in the nonneoplastic populations. A good correlation between the percentage of cells calculated to be in the S phase of the cell cycle and the expected clinical behavior of the tumors was observed. In those lymphomas in which the S-phase percentages could be calculated, 11 of 13 low-grade lymphomas had less than 5% of the cells in S phase, and 7 of 10 high-grade lymphomas had greater than 5% of the cells in S phase. Thirteen of 21 neoplastic cases in which Coulter volume determinations were performed could be distinguished from the nonneoplastic controls on the basis of their modal volume. Although some correlation was observed between light scatter of ethanol-fixed cells and Coulter volume measurements on unfixed cells, light scatter was found to be less discriminatory. Altogether, by all three flow parameters studied, 26 of 30 (87%) of the neoplastic cases could be distinguished from nonneoplastic controls.

DNA Replication↗

Cell surface markers on lymphoid cells from Warthin's tumors.

T- and B-cell markers were studied on suspensions of lymphoid cells obtained from two Warthin's tumors. Each tumor was composed predominantly of T- lymphocytes and a smaller percentage of B-lymphocytes with a polyclonal distribution of their surface immunoglobulin. These results do not differ from those obtained in normal or reactive lymph nodes. Together with the finding of normal lymph node structures in these tumors, our findings support the concept that the lymphoid component of Warthin's tumor represents pre-existing lymph node tissue.

Adenolymphoma↗

Multiparameter interpretative reporting in diagnostic laboratory hematology.

Accurate diagnosis and classification of hematologic malignancies (acute leukemias and chronic lymphoproliferative disorders) requires a multiparameter approach including peripheral blood analysis, bone marrow examination, and immunophenotyping. We have designed knowledge-based computer systems for interpretation of the hemogram and peripheral blood smears, analysis of flow cytometric immunophenotyping panels, and morphologic assessment of bone marrow specimens. The 3 modules share a relational database which includes pertinent clinical history in addition to the laboratory results. The bone marrow module automatically writes a complete interpretative report with a final diagnosis by searching all of the databases for appropriate clinical, peripheral blood, and immunophenotyping information. The ability of the 3 modules to interact, and the quality of the interpretative reports were tested on 100 consecutive patients with leukemia. The final diagnosis made by the bone marrow system agreed with the hospital diagnosis in 94 cases and the authors' interpretation in 99 of 100 cases.

Artificial Intelligence↗

Multiparameter case studies using knowledge-based systems in hematology.

Knowledge-based systems in diagnostic medicine are often used for teaching medical decision making. We have extended the educational value of our suite of hematology decision support systems (peripheral blood analysis, flow cytometry immunophenotyping and DNA analysis, and bone marrow morphology) by creating case studies in a hypertext format. The case studies use the knowledge-based system screens as a background. Digitized images of blood and bone marrow smears from the teaching cases can be accessed on-line. The case studies, which are designed primarily for technologists and physicians, emphasize the proper multiparameter approach to hematopathology diagnosis.

Decision Support Techniques↗

Are normative expert systems appropriate for diagnostic pathology?

Conceptual models for diagnostic reasoning proposed in the medical literature are presented to stimulate discussion about the issue of the appropriateness of probabilistic knowledge-based systems for medical diagnosis. Evidence is presented to corroborate the authors' view that diagnosis is a problem-solving task, rather than a decision-making task. In the authors' opinion, probabilistic reasoning is better suited to situations dealing with choices for clinical intervention, rather than to those dealing with determining the correct diagnosis. A critique is given of a diagnostic Bayesian expert system for lymph node pathology. In empirical studies, diagnostic Bayesian systems have been shown to typically list the correct diagnosis as the program's first choice 60% to 70% of the time. One reason for this undistinguished level of diagnostic performance is that Bayesian systems are not designed to represent and use knowledge the same way that an expert does.

Bayes Theorem↗