Feeling controlled or being in control? Apps for self-management among older people with neurological disability.

PURPOSE: The aim of this paper was to describe how people living with a neurological disability such as multiple sclerosis, Parkinson's disease and stroke reason regarding using apps to facilitate self-management in everyday life. MATERIAL AND METHODS: A qualitative research approach with a focus group methodology was used. The sample comprised 16 participants, 11 men and 5 women, with an average age of 64 years (ranging from 51-80 years). Six participants were diagnosed with multiple sclerosis, six with Parkinson's disease and four with stroke. Data were analyzed using thematic analysis, which is a method for identifying, analyzing and reporting patterns. RESULTS: The results formed two themes. The first theme "using apps to have control of my health" comprises two subthemes; "monitor and take responsibility for a healthy lifestyle" and "compensate to facilitate everyday life". The second theme "using the app as a tool and means for communication" also comprised two subthemes; "dare to trust the app" and "feeling safe when sharing information with health care professionals". CONCLUSIONS: The use of apps put increased responsibility on the person and had the possibility to make them more involved in their own care. The use of an app can facilitate a healthy lifestyle and help to monitor disease-specific symptoms. In order to be able to use apps for communication with the health care sector legislation and safety issues need to be considered.Implications for rehabilitationApps can be used for self-management if they are safe and can be trusted.People with neurological disabilities want to be involved in their healthcare and needs to be addressed by health care professionals.The use of apps grasp over a wide variety of areas this is something that may be considered in health care and something that can be addressed by interdisciplinary approaches.Ordinary health-oriented apps and disease-specific apps were used differently and for different purposes.

The Use of Apps for Health in Persons with Multiple Sclerosis, Parkinson's Disease and Stroke - Barriers and Facilitators.

INTRODUCTION: The importance of mobile health has increased during recent years but few studies have described the use of apps among persons with neurological disabilities. AIM: The aim of this paper was to describe how persons ageing with a neurological disability experience barriers and facilitators in relation to using apps in everyday life. METHOD: A qualitative approach was used. 16 persons with neurological disorders participated in two group discussions. Data were analyzed by content analysis. RESULTS: The analysis formed four categories; Impairments make apps harder to use, Use of apps is increased by learnability and sharing, Valuating the information in an app, and Apps act supportive and motivating. CONCLUSION: The participants used apps in the same way as persons without disabilities. Impairments and trustworthiness were perceived as barriers, which need to be acknowledged when developing apps for this population. Use of apps was facilitated by the possibility to share data and to connect with others. Apps may have the potential to improve self-management for persons ageing with disabilities but further research is needed.

Pathology of autoimmune myelofibrosis. A report of three cases and a review of the literature.

We identified 3 patients with autoimmune myelofibrosis (AM) lacking American Rheumatism Association criteria for systemic lupus erythematosus (SLE). They had 1 or 2 cytopenias and lacked serologic evidence for SLE. Autoimmune features included psoriatic arthritis and positive direct Coombs test (DCT) result, DCT-positive autoimmune hemolytic anemia, and synovitis with polyclonal hypergammaglobulinemia. Bone marrow biopsy specimens from each patient were evaluated by routine morphologic and immunohistochemical examination. They demonstrated marked hypercellularity (2 cases) or hypocellularity (1 case), moderate erythroid hyperplasia (all cases) with left-shifted maturation (2 cases), intrasinusoidal hematopoiesis (all cases), slightly to moderately increased megakaryocytes (2 cases), and grade 3 to 4 reticulin fibrosis (all cases). All lacked basophilia, eosinophilia, bizarre megakaryocytes, clusters of megakaryocytes, and osteosclerosis. Mild to moderate bone marrow lymphocytosis was noted in all cases. In 2 cases, increased small T cells and B cells formed nonparatrabecular, loose aggregates. AM is a clinicopathologic entity that may lack features of SLE. Loose aggregates of bone marrow T and B lymphocytes and the absence of morphologic and clinical features of myeloproliferative disease or low-grade lymphoproliferative disease are clues that distinguish AM from better known causes of bone marrow fibrosis.

High-grade transformation of chronic lymphocytic leukemia and low-grade non-Hodgkin's lymphoma. Genotypic confirmation of clonal identity.

The abrupt appearance of a high-grade tumor in patients with low-grade malignant lymphoma usually is associated with an accelerated clinical disease course. The high-grade lymphoma may take a variety of histologic forms and often, but not always, represents evolution of the original low-grade disease, as shown by immunophenotypic or immunogenotypic studies. The authors describe the transformation of a variety of low-grade B-cell neoplasms to high-grade tumors in four patients. The initial diagnoses included chronic lymphocytic leukemia and mantle cell lymphoma in one patient each and low-grade follicular lymphoma in two patients. The high-grade tumors were classified as lymphoblastic lymphoma in one patient and small noncleaved cell lymphoma in two patients. The high-grade component manifests primarily in the peripheral blood as circulating blast-like cells consistent with large-cell lymphoma in the remaining patient. In each case, immunophenotypic studies showed identical monoclonal surface immunoglobulin expression on the low- and high-grade tumors. Immunoglobulin heavy chain gene and kappa light chain gene studies showed identical clonally rearranged bands in paired samples from three of the four patients, a finding indicative of clonal identity. Unexpectedly, dissimilar immunoglobulin light and heavy chain gene rearrangements were detected in the paired samples from one patient with previously diagnosed follicular lymphoma, making the relationship of the two tumors from this patient uncertain; however, additional Southern blot analysis of the bcl-2 gene showed identical rearrangements in both lesions. Furthermore, polymerase chain reaction across the t(14;18) major breakpoint region in both tumors amplified nucleotide fragments of identical size, confirming the clonal identity of the low- and high-grade lymphomas despite the divergent immunoglobulin gene studies. These studies show that low-grade malignant lymphomas of small lymphocytic, mantle cell, or follicular small cleaved cell types may assume high-grade morphologic characteristics, that this change is the result of transformation of the preexisting low-grade malignant neoplasm, and that this progression, like typical Richter's syndrome, is associated with a dramatically accelerated clinical course. In addition, these studies confirm previous reports that disparate immunoglobulin light and heavy chain gene rearrangements are not necessarily an indicator of different cellular origins, and additional genotypic studies occasionally may be required to show the clonal identity of the cell population involved in these morphologic transformations.(ABSTRACT TRUNCATED AT 400 WORDS)

Immunohistologic studies of bone marrow biopsies on frozen sections: an analysis of 42 cases.

An immunohistologic study of bone marrow biopsy frozen sections from 42 cases involved by a variety of reactive and neoplastic disorders is presented. Thirteen cases also were studied using other methods, including cytochemistry, surface marker analysis of cell suspensions, and/or DNA hybridization. Thirty-four of 42 cases (81%) were adequately phenotyped on frozen tissue using a panel of antibodies for hematolymphoid-associated antigens. The immunostains from the remaining eight cases were unsatisfactory, primarily as a result of heavy background staining. Eighteen cases were lymphoproliferative disorders of B-cell phenotype and 12 of these showed surface monotypic immunoglobulin expression by the frozen section technique. Six cases showed B- or pre-B-cell antigens but no surface immunoglobulins. Of the remaining 16 patients, two cases showed myeloid markers and three showed T-cell phenotype. Nine cases showed a mixture of polyclonal B- and T-cell populations. Keratin was demonstrated in a single case of metastatic carcinoma included in the study. These results indicate that the majority of hematopoietic processes can be successfully phenotyped on bone core frozen sections and demonstrate the usefulness of immunohistologic study of the frozen bone marrow biopsy specimens, especially when the specimens for other modalities are not available or are inadequate. The keys to achieving the best results from the frozen bone marrow immunohistochemistry were the gentle handling of the specimens and the preparation of high-quality, cryostat-cut frozen sections.

Immunoarchitecture of normal human bone marrow: a study of frozen and fixed tissue sections.

To provide baseline information on the immunoarchitecture of normal bone marrow, we studied cryostat-cut, frozen, and paraffin-embedded, fixed tissue sections prepared from 21 core biopsies of normal bone marrow obtained during bone marrow harvests for transplantation. A large panel of antibodies was applied that included, for frozen tissue, Leu-6 (CD1), T11 (CD2), Leu-3a (CD4), Leu-1 (CD5), Leu-2a (CD8), J5 (CD10), My7 (CD13), Leu-11 (CD16), B4 (CD19), B1 (CD20), B2 (CD21), Tac (CD25), My9 (CD33), T200 (CD45), NKH-1 (CD56), kappa and lambda chains, beta F1, Ki-67, HLA-DR, TQ1, and keratin, and for fixed tissue, leukocyte common antigen (CD45), L26 (CD20), LN1 (CDw75), LN2 (CD74), LN3, LN4, LN5, MB1 (CD45R), MB2, MT1 (CD43), MT2 (CD45R), UCHL1 (CD45R0), BM1, Ki-1 (CD30), Leu-M1 (CD15), lysozyme, KP1 (CD68), actin, S100, neuron-specific enolase, vimentin, and keratin. On fresh-frozen sections CD19 and CD2 were the most reliable and sensitive markers for B and T cells, staining 5% and 9% of marrow cells, respectively. Immunoglobulins generally showed heavy background staining, which frequently precluded an accurate assessment. The CD4 to CD8 ratio in the bone marrow was reversed from that of peripheral blood. On fixed tissues, leukocyte common antigen was found in 14% of the marrow cells, corresponding roughly to the lymphocyte population. L26, a pan-B-cell marker, stained 3% of the marrow cells. Among the other B-cell markers, LN1 and MB2 stained a large number of cells (40% to 70%), indicating reactivity with cells of the myeloid or erythroid series in addition to lymphocytes. Among the T-cell markers, UCHL1 and MT1 stained 66% and 50% of the cells, respectively, which could be explained by their cross-reactivity with myeloid cells. Nonspecific myelomonocytic markers (Leu-M1, KP1, and lysozyme) also showed reactivity in a high percentage of cells. No particular architectural distribution patterns of B or T lymphocytes were noted in either frozen or fixed bone marrow specimens. The results of this study provide normal baseline data for the immunohistologic application of hematopoietic and lymphoid markers on frozen or fixed bone marrow biopsy specimens.

Splenic involvement by aggressive malignant lymphomas of B-cell and T-cell types. A morphologic and immunophenotypic study.

To determine whether there are any consistent morphologic differences between B-cell and T-cell aggressive non-Hodgkin's lymphomas of the spleen, the authors analyzed 16 spleens involved by mixed cell (1 case) or large cell (15 cases) lymphomas. Immunologic data were derived from cell suspensions or frozen tissue in each case. Five cases had a T-cell phenotype, and 11 were B-cell. Morphologic features favoring a T-cell phenotype included epithelioid histiocytic reactions, confinement of the lymphomas to the splenic T-zones (periarteriolar lymphoid sheath and marginal zone), and clear cell or polymorphous cytologic features. Features favoring a B-cell phenotype included multiple discrete nodules in the white pulp, large coalescent tumor nodules in association with small lymphocytic lymphoma, and large non-cleaved or immunoblastic plasmacytoid cytologic characteristics. Four cases were unusual because most neoplastic large cells were distributed diffusely or formed only small aggregates in the red pulp without definite tumor masses or nodules involving the white pulp. Because of this distribution and the frequently encountered erythrophagocytosis by benign-appearing histiocytes, these cases resembled malignant histiocytosis. A T-cell phenotype was predicted for all four cases; however, only one case, a lymphoma with polymorphous cytologic characteristics, was of T-cell lineage. The other three cases were of B-cell lineage. The authors' results indicate that in most instances the B-cell or T-cell nature of aggressive splenic lymphomas is predictable from the distributional and cytologic features. As in lymph nodes, there are cases for which the morphologic characteristics of B-cell and T-cell lymphomas are indistinguishable.

Monocytoid B-cell lymphoma in a patient with human immunodeficiency virus infection. Demonstration of human immunodeficiency virus sequences in paraffin-embedded lymph node sections by polymerase chain reaction amplification.

There is a significantly increased incidence of malignant lymphoma in patients with acquired immunodeficiency syndrome (AIDS). The lymphomas are usually of a high grade and of B-cell phenotype. While the frequent presence of reactive monocytoid B lymphocytes in patients with AIDS-related lymphadenopathy has recently been documented in several studies, to our knowledge, there are no reported cases of monocytoid B-cell lymphoma, the neoplastic counterpart of monocytoid B lymphocytes, in patients with AIDS. We now describe a human immunodeficiency virus (HIV)-positive patient with HIV-related lymphadenopathy in whom monocytoid B-cell lymphoma developed during the course of his disease. The morphologic and immunologic features of the lymphoma were characteristic of monocytoid B-cell lymphoma, and the involved lymph node exhibited a reversed CD4/CD8 ratio. Moreover, using the polymerase chain reaction, we were able to demonstrate HIV genome in DNA extracted from the lymph node tissue. To our knowledge, this is the first report of a case of monocytoid B-cell lymphoma occurring in an HIV-positive patient and in which we were able, by using a sensitive molecular biologic technique, to demonstrate HIV sequence in paraffin-embedded, fixed lymph node sections.

Genotype and phenotype: a practical approach to the immunogenetic analysis of lymphoproliferative disorders.

Determination of cell lineage and clonality in lymphoproliferative disorders (LPD) is greatly enhanced by molecular genetic analysis in conjunction with morphologic and immunologic techniques. We now report on a technique in which we used cryostat-cut, fresh-frozen sections (CCFFS) prepared from tissues in a manner that allows DNA hybridization studies to be coordinated readily with routine morphologic and immunohistologic studies. Thirty-seven cases representing a broad spectrum of reactive and malignant LPD were examined with this method. Samples of DNA were extracted from frozen sections, subjected to Southern blot hybridization, and probed for rearrangements of the immunoglobulin (Ig) heavy-chain and the kappa and lambda light-chain genes, as well as for the T-cell receptor beta-chain gene. We also evaluated the effects of (1) diagnostic category of LPD, (2) volume of the tissue sample, and (3) fibrosis, necrosis, and ice crystal artifacts in the sample on the recovery of DNA. Ice artifact and sample size had the greatest negative impacts on the quantity and condition of DNA recovered. Of 19 samples involved by B-cell LPD, the results of immunogenetic studies were consistent with the immunophenotypes in all but one case. Of the T-cell lymphomas from which sufficient DNA was available (three out of five of the T-cell cases), all showed rearrangements of the T-cell beta-chain gene. In order to reduce sample processing time, we evaluated alternate blot hybridization methods, rapid alkaline transfers, and direct hybridization of synthetic oligonucleotides in dried agarose gels, and found that they decreased the time required for hybridization studies. In summary, the use of CCFFS as the source of DNA allows study of gene rearrangements and, at the same time, preserves frozen-tissue blocks in tumor banks for further immunologic studies. The development of time-effective methods will make the routine use of molecular-genetic analysis more practical in the diagnostic hematopathology laboratory.

Analysis of antigen receptor gene rearrangements in ethanol and formaldehyde-fixed, paraffin-embedded specimens.

Molecular hybridization analysis of DNA prepared from frozen specimens obtained from patients with lymphoproliferative disorders has aided in the determination of the lineage and clonality of the neoplastic cells in many cases. We investigated whether high molecular weight DNA suitable for nucleic acid hybridization studies could also be prepared from fixed, paraffin-embedded material. After selecting nine representative cases, we extracted DNA from frozen sections by using standard methods, and from ethanol-fixed tissue in paraffin blocks. The yields of DNA from ethanol-fixed blocks were similar to yields from frozen tissue. DNA from frozen and ethanol-fixed tissues was subjected to Southern blot hybridization and probed for rearrangements of immunoglobulin heavy, and kappa, and lambda light chain genes, as well as for the T cell receptor beta-chain gene. In each of the cases, comparable results were obtained, regardless of the source of DNA. DNA extracted from ethanol-fixed blocks stored for 2 years gave identical results. We also prepared DNA from formaldehyde-fixed, paraffin-embedded tissue obtained from six of the patients. Five of the specimens yielded spoolable DNA (average recovered, 313 micrograms), but the DNA was degraded more than that obtained from the frozen or ethanol-fixed specimens. Formaldehyde-treated DNA gave variable results in Southern blot hybridization studies, and less than half of the results were interpretable. We conclude that ethanol-fixed, paraffin-embedded tissues provide an excellent source of DNA for nucleic-acid hybridization studies, and that they are easily handled and stored.

The in-vitro response of CD2-positive acute myelogenous leukemia to proliferation and differentiation inducing agents.

Acute mixed lineage leukemias (MLL) are a heterogeneous group of acute leukemias that express morphologic and/or immunophenotypic features of more than one hematopoietic cell line. The ontogenetic significance of this mixed lineage expression is unclear. We therefore studied the conviction of the lineage commitment in a group of MLL by examining the in-vitro response of five CD2+ (E-rosette receptor) acute myelogenous leukemia (AML) to a panel of proliferation and differentiation-inducing agents. Three of the five CD2+ AML were TdT-positive. Antigen receptor gene studies revealed no rearrangements at either the T beta or immunoglobulin heavy chain gene loci in any case. When blast-enriched cell populations were placed in short term suspension cultures with PHA, IL-2, PHA + IL-2, GM-CSF or TPA, three of the leukemias responded in a similar fashion while the remaining two cases showed no response. In the three MLL that responded to the in-vitro culture manipulations, features indicative of differentiation along the monocytic lineage pathway were observed. This differentiation was not pronounced in the presence of the phorbol ester TPA, and was manifested by loss of CD2 and CD7 expression, continued expression of myeloid antigens, and the development by the blasts of morphologic and cytochemical characteristics of monocytic cells. None of the five MLL showed any evidence of induced maturation along the T-lymphocyte line of differentiation with any of the agents used. rGM-CSF was the only exogenously added agent to induce proliferation; the proliferative response was slight and was seen in only one of the five leukemias. Therefore, the phenotypic expression of CD2 and CD7 in blasts from MLL is not indicative of irreversible commitment to T-lymphocyte development. The in-vitro loss of T-cell antigens in concert with the development of monocytic features in three of the five CD2+ AML in this study suggests the leukemic cells were preferentially committed to a non-lymphoid lineage differentiation pathway.

Imprint cytology of non-Hodgkin's lymphomas based on a study of 212 immunologically characterized cases: correlation of touch imprints with tissue sections.

The classification of non-Hodgkin's lymphomas (NHLs) has been traditionally based on analysis of histologic sections and has been supplemented more recently by immunologic marker studies. It was the purpose of the present study to illustrate, side-by-side, sections and Romanowsky-stained imprints from the same surgical specimen from practically all categories of immunophenotyped NHLs, including rare and atypical variants that were difficult to classify from the histologic sections alone. Our results indicate that imprint cytology may reveal nuclear and cytoplasmic details not discernible in even the best tissue sections and that it may be selectively helpful in contributing to the classification of NHLs. Our results also show that the relative value of imprint cytology in the classification of malignant lymphomas varies greatly among categories. Specifically, we have found that imprints assist in three ways: the recognition of plasmacytoid features in small cell lymphocytic lymphomas, the recognition of plasmacytoid immunoblastic lymphoma, and the differentiation between NHLs which may be difficult to distinguish histologically. These include (1) small lymphocytic lymphoma versus lymphocytic lymphoma of intermediate differentiation, (2) true histiocytic malignancies versus large cell malignant lymphomas with abundant cytoplasm and/or phagocytosis, (3) anaplastic myeloma versus plasmacytoid immunoblastic lymphoma, (4) large noncleaved versus plasmacytoid immunoblastic lymphoma, (5) lymphoblastic lymphoma versus diffuse small cleaved cell lymphoma, and (6) lymphoblastic lymphoma versus small noncleaved cell lymphoma. Lymph node imprints are easy to prepare and readily interpretable by those experienced in the study of abnormal blood and bone marrow films. Their value as an ancillary methodology aimed at optimal accuracy in the classification of NHLs should be recognized.

Cytogenetic studies of Hodgkin's disease. Analysis of involved lymph nodes from 12 patients.

Cytogenetic studies were performed on 12 involved lymph nodes from Hodgkin's disease patients utilizing conditioned medium from 12-O-tetradecanoylphorbol-13-acetate-staphylococcus enterotoxin A induced mononuclear cells. The majority of cells analyzed had a normal karyotype. An unusually high rate of nonclonal karyotypic abnormalities was noted in most cultures. Clonal abnormalities involving chromosomes 3 and 21 were noted in two patients. Cytogenetic analysis of cultures stimulated with conditioned medium or specific growth factors may lead to a better understanding of the genetic mechanisms involved in Hodgkin's disease.

Monocytoid B-cell lymphoma: its evolution and relationship to other low-grade B-cell neoplasms.

Monocytoid B-cell lymphoma (MBCL) is a newly recognized B-cell neoplasm of uncertain histogenesis. The cytologic features of the neoplastic monocytoid B lymphocytes are virtually identical to those of hairy cell leukemia (HCL). As with HCL, progression of MBCL to a higher histologic grade is very unusual. However, whereas circulating leukemic cells are a characteristic feature of HCL, peripheral blood involvement has not been reported in MBCL. We recently studied a patient with MBCL of the spleen and axillary lymph nodes who developed peripheral blood involvement by MBCL cells. Unlike the cells of HCL, the circulating MBCL cells exhibited strong acid phosphatase activity that was tartrate sensitive. The leukemic cells had the antigenic phenotype IgM lambda, CD20+, CD11c+, CD5-, CD25(TAC)-, and PCA-1-. Immunogenetic studies of both lymph node and peripheral blood cells revealed identical immunoglobulin heavy-chain gene rearrangements. When compared with a series of HCL, the immunophenotype was similar except for the absence of PCA-1 and TAC. Progression of the MBCL to a large cell lymphoma, also expressing IgM lambda, was documented in an abdominal lymph node of this patient. Therefore, although rare, peripheral blood involvement by lymphoma cells may occur during the course of MBCL and should be distinguished from HCL with cytochemical and immunophenotypic studies. In addition, comparison of the clinical, pathologic, and immunologic features of MBCL with those of other low-grade B-cell neoplasms suggests that a close lineage relationship exists between MBCL and HCL.

Monocytoid B-cell lymphoma. Clinicopathologic study of 21 cases of a unique type of low-grade lymphoma.

The morphologic and immunologic features of three cases of an unusual and distinct B-cell lymphoma were recently described and termed monocytoid B-cell lymphoma (MBCL) because of the striking resemblance of the neoplastic cells to reactive monocytoid B-lymphocytes. The morphologic spectrum and the clinical behavior of MBCL were investigated in a series of 21 patients. This study indicates that patients with MBCL usually present with lymphadenopathy and Stage I or II disease. MBCL also occurs at extranodal sites including the salivary gland. Because four of the patients with MBCL had Sjögren's syndrome with characteristic laboratory profiles, these results raise the possibility that there may be a relationship between MBCL and Sjögren's syndrome. Eight patients were male and 13 female (M:F = 1:1.6), and MBCL primarily involved the elderly (median age, 66 years). The most striking clinical findings were high percentages of complete remissions and long survival times indicating that MBCL is a low-grade lymphoma. Of 21 patients investigated, 18 were in complete remission at the time of completion of this study. Two patients died with the disease and one was lost to follow-up. Patients with localized MBCL may have a better survival rate than those with generalized disease. Like other low-grade lymphomas, MBCL can progress to a higher grade lymphoma of large cell type. Unlike other low-grade lymphomas, in MBCL splenomegaly, bone marrow involvement, and leukemic conversion are uncommon.

T-cell-rich lymphoproliferative disorders. Morphologic and immunologic differential diagnoses.

To differentiate peripheral T-cell lymphomas (PTCL), the authors evaluated the results of T11 monoclonal antibody studies on consecutive cell suspensions prepared from 509 lymph nodes from various lymphoproliferative disorders (LPD). They used T11 (CD2) positivity to identify those LPD in which the content of T cells was high. There were 266 (52%) cell suspensions which contained more than 50% T11-positive cells. More than 75% of the following non-Hodgkin's lymphomas had over 50% T11-positive cells: diffuse mixed cell (DM), diffuse atypical poorly differentiated lymphocytic and lymphoblastic lymphomas; mycosis fungoides; and true histiocytic lymphoma. Eleven cell suspensions had more than 90% T11-positive cells; four were involved by B-cell lymphomas. The cell suspensions prepared from nine of 14 diffuse large cell lymphomas of the T-cell type had more than 50% T11-positive cells. Of these, three of five cases of the polymorphous subtype had fewer than 50% T11 cells, but six of seven lymph nodes of the clear-cell type had more than 50% T11-positive cells. Each of seven DM samples of the T-cell type contained over 50% T11 cells; none had a polymorphous appearance. In the 112 cases of reactive LPD studied, more than 75% of cases of necrotizing lymphadenitis, dermatopathic lymphadenitis, angioimmunoblastic lymphadenopathy, and those with lymph nodes with no specific reactive pattern had more than 50% T11-positive cells. The authors' findings indicate that T11 positivity is a reliable T-cell marker in reactive and neoplastic LPD except for those cases of PTCL with a polymorphous appearance; these tend to lose T11-expression. A multi-parameter diagnostic approach is required in the following LPD: (1) PTCL which are T11-negative; (2) PTCL of small lymphocytic type having an unremarkable T-cell phenotype; (3) SIg-negative B-cell lymphomas which are rich in nonneoplastic T cells; (4) non-Hodgkin's lymphomas with minimal disease which are rich in reactive T cells; and (5) polymorphous large cell proliferations.

Variability in interpretation of immunohistologic findings in lymphoproliferative disorders by hematopathologists. A comprehensive statistical analysis of interobserver performance.

Eight hematopathologists independently reviewed 56 consecutive cases of benign and malignant lymphoproliferative disorders (LPD) to determine: (1) the degree of interobserver agreement on the interpretation of immunologic findings on fresh-frozen sections alone and on that of the immunologic findings in conjunction with corresponding hematoxylin and eosin (H & E)-stained histologic sections; (2) whether prior knowledge of morphologic characteristics influences the interpretation of immunohistologic sections; (3) whether immunologic phenotype could be predicted reliably based solely on study of histologic sections; and (4) the significance of immunologic data as an aid in the interpretation of histologic sections. The study was carried out in three independent review sessions consisting of (1) review of immunohistologic sections only, (2) review of the same immunohistologic sections together with histologic sections, and (3) review of the histologic sections alone. A consensus diagnosis was defined as agreement of five or more pathologists on the final diagnosis and identification of the immunophenotype. When the authors compared the total number of major disagreements in the first review session with those in the second, the accuracy of the determination of immunophenotype in the second session was clearly superior (P less than 0.05). Similarly, the total number of major disagreements in the second review session was significantly lower than that in the third review session (P less than 0.001). When histologic diagnoses in the second session were compared with those in the third session, it became apparent that the immunologic data helped the pathologist to correct major misinterpretations in 14 cases (25%). This study is the first to demonstrate quantitatively that (1) knowledge of morphologic features influences and greatly enhances the accuracy of the interpretation of immunologic findings, (2) the immunophenotype of LPD cannot be predicted based on morphologic findings alone, and (3) immunologic findings improve the accuracy of interpretation of histologic findings in situations in which a diagnosis cannot be made from morphologic features only.

Carcinogenicity and haemoglobin synthesis induction by cytidine analogues.

We investigated 5-azacytidine and five of its analogues for: (1) carcinogenicity, in the male Fischer rat; (2) toxicities using changes in rat weights in vivo and a cytotoxicity assay in vitro; and (3) haemoglobin gene expression, using minor haemoglobin synthesis in sheep, mice and rats. 5-Azacytidine was found to be a complete carcinogen. It increased the incidence of testicular tumours as well as non-testicular tumours in rats treated for 12 months. 5-Azacytidine also had hepatic tumour promoting properties and was able to induce transplacental carcinogenesis when administered to pregnant rats on day 21 of timed pregnancies. None of the other 5 analogues that were tested appeared to be carcinogenic in small experiments. All the analogues which are known to have hypomethylating activity were found to be cytotoxic in vitro; the most potent being 5-azacytidine. As judged by decreased rat weight compared to untreated controls, the fluorinated cytidine analogues and 5'-deoxyazacytidine were more toxic than 5-azacytidine. Altered haemoglobin synthesis was seen in rats and DBA/2J mice, but not in sheep. In mice, where the clearest haemoglobin changes were noted, an increase in minor haemoglobin synthesis was found using both high and low doses of 5-azacytidine, and with 5,6-dihydro-5-azacytidine and 5-aza-2'-deoxycytidine. These last two analogues appear to be relatively non-toxic, noncarcinogenic in these experiments, and retain haemoglobin activating properties with a potency similar to that of 5-azacytidine.