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Biomedical subjects

A G Stansfeld

Publications and source records attributed to A G Stansfeld.

At least 55 records · Page 3Linked to original sources

The management of stage II supradiaphragmatic Hodgkin's disease at St. Bartholomew's Hospital. A retrospective review of 114 previously untreated patients over 14 years.

Between January, 1968 and July, 1981, 114 consecutive patients with newly diagnosed supradiaphragmatic stage II Hodgkin's disease were treated at St. Bartholomew's Hospital on the basis of pathologic staging (PS) in 56 (47 IIA, 9 IIB) and clinical staging (CS) in 58 (23 IIA, 35 IIB). Complete remission (CR) was achieved in 104 (91%) patients, of whom 27 have relapsed. Ninety-three patients remain alive, the cumulative predicted survival at 10 years being 81%, with a minimum follow-up of 2 years and a maximum of 15 years. Mantle radiotherapy (RT) was prescribed for 76 patients, of whom 67 (88%) entered CR. The duration of CR correlated inversely with the presence of intrathoracic lymphadenopathy. No patient with PS IIA and a normal chest radiograph has yet relapsed, whereas in contrast, a rising probability of relapse is related to increasing volume of intrathoracic lymphadenopathy. Combination chemotherapy (CT) with mustine, vinblastine, procarbazine, and prednisone (MVPP) was prescribed to 38 patients, 27 with "B" symptoms and 11 stage IIA patients with "unfavorable" features. CR was attained in 32 (84%) patients, of whom 24 subsequently proceeded to mantle irradiation. Only one of these has relapsed, compared to two of eight patients who did not receive adjuvant RT (P = NS). The duration of remission of patients receiving combined modality therapy (CT + RT) or CT alone was significantly longer (P less than 0.05) than that of patients receiving RT alone, in spite of the fact that the CT + RT group comprised predominantly patients with unfavorable features.

Adolescent↗

Caribbean T-cell lymphoma/leukemia.

Caribbean T-cell lymphoma/leukemia (CATL) is a recently described neoplasm similar to Japanese adult T-cell leukemia/lymphoma, but it occurs in patients born in a different geographic region. Four adult Black West Indian women with CATL were studied using a multiparameter approach, including clinical, hematologic, pathologic, and immunologic investigations. The disease was usually characterized by adenopathy (with or without hepatosplenomegaly), peripheral blood involvement, hypercalcemia often in the absence of gross bony lesions, and a poor prognosis. The neoplastic cells were pleomorphic with marked nuclear irregularity of a multilobated or more cerebriform type. Lymph node biopsies demonstrated a diffuse pleomorphic lymphoma with variable degrees of nuclear irregularity and transformation. Marrow involvement consisted of focal nodules or, more commonly, scattered atypical lymphoid cells. Marrow biopsies also often demonstrated osteoclastic activity. Cases were all of T-cell origin, most commonly of T-helper phenotype, although there was some phenotypic heterogeneity. All patients had antibodies to the human T-lymphoma/leukemia virus.

Adult↗

Lymphocytic lymphoma/B-chronic lymphocytic leukaemia--an immunohistopathological study of peripheral B lymphocyte neoplasia.

Twenty seven patients with malignant lymphoma of lymphocytic type/B-chronic lymphocytic leukaemia (ML, L/B-CLL, Kiel classification) diagnosed from lymph node and splenectomy specimens were studied histologically and immunologically. Lymph node biopsies showed a diffuse effacement of normal architecture by small round lymphocytes usually with scattered proliferation centres (PC). A1 spleens showed white pulp with or without red pulp involvement, sometimes with tumour nodules present. PC-like cells or PC were only found in the white pulp or tumour nodules. Studies of 13 specimens using the ABC immunoperoxidase technique on frozen sections with a large panel of monoclonal antibodies showed that although a part of the monoclonal B cell neoplasm, the proliferation centres or splenic white pulp have a different phenotype from the surrounding cells. Some of these phenotypic changes are similar to those reported with in vitro induction of "maturation" of ML, L/B-CLL cells. The implications for normal B-cell development are discussed. In contrast to reported peripheral blood findings, T cells, predominantly of T helper phenotype in lymph nodes, were present but usually not numerous.

Antibodies, Neoplasm↗

Characteristics of Sternberg-Reed, and related cells in Hodgkin's disease: an immunohistological study.

A panel of monoclonal antileucocyte antibodies was used in a study of Hodgkin's disease (HD) to explore the phenotypic characteristics of Sternberg-Reed and related cells (collectively termed HD cells). Cryostat preparations of 31 lymph nodes and 2 spleens were obtained from 30 patients with active HD. The histological diagnoses were: lymphocyte predominance (LP), 4 patients; nodular sclerosis (NS), 22; mixed cellularity (MC), 2; lymphocyte depletion (LD), 2. The monoclonal antibodies used were: OKT3, T11, Leu-1 (pan T cell specific); Leu-3A (T "helper" specific); Leu-2A, OKT8 (T "suppressor" specific); immunoglobulin (Ig) antibodies: anti kappa and lambda light chains, anti mu and delta heavy chains; B1 (anti B lymphocyte); CA2-11 (anti HLA-DR); OKM1, Mo-2 (anti myeloid/monocyte); OKT9 (anti transferrin receptor); Leu-7 (anti "NK" cell) and J5 (anti common ALL antigen). Reactions with peanut lectin (PNL) were also studied. The reactions were developed using a modified "ABC" immunoperoxidase technique. Specific attention was paid to the cell surface phenotype and anatomical localisation of HD cells in relation to surrounding T and B lymphocytes. HD cells formed distinct "rosettes" with T cells of "helper" phenotype although in 3 cases (1: LP, 2: NS) Leu-7 positive cells formed a prominent component of these interactions. In partially involved lymph node and spleen, HD cells were prominently distributed in a perifollicular distribution. In addition follicular mantle zones were frequently infiltrated by HD cells, the degree of ensuing destruction being related to the extent of lymph node effacement by HD. In 2 cases (1: NS, 1: LD) HD cells expressed clear, positive reactions with B1 although in neither of these cases nor in any other instance, was surface Ig expressed on the HD cell surface. The great majority of HD cells reacted positively with both OKT9 and, as previously reported, with anti HLA-DR antibody. In addition, HD cells demonstrated intense surface and cytoplasmic staining with PNL. HD cells were negative with all other antibodies. On the basis of these findings, no lineage specificity can confidently be attributed to the HD cell. However, the pattern of immunohistological reactions suggest that it is related to a cell of B follicular origins.

Adolescent↗

Correlation of transferrin receptor expression with histological class and outcome in non-Hodgkin lymphoma.

The proportion of lymphocytes from patients with non-Hodgkin lymphoma (NHL) expressing transferrin receptors in biopsy material from lymph-nodes assayed by binding of the monoclonal antibody OKT9 correlated significantly with the histological class of the tumour. High-grade lymphomas contained 22.5% (range 3-57%) OKT9-positive lymphocytes, and low-grade lymphomas contained 2.5% (range less than 1-22). Since histological class of lymphoma is an important factor in survival, it was expected and confirmed that OKT9 levels were related to survival in these patients. Transferrin receptor is expressed by growing cells. The correlates observed in this series of NHL suggests a relation between transferrin receptor and either the growth fraction, or factors affecting the growth fraction, of the tumour.

Antibodies, Monoclonal↗

The cellular content of non Hodgkin lymphomas: a comprehensive analysis using monoclonal antibodies and other surface marker techniques.

Five samples of tonsil, 10 reactive lymph nodes and 65 consecutive cases of non-Hodgkin lymphoma (NHL) were evaluated in suspension phenotyping with the monoclonal antibodies alpha Leu-I, alpha Leu-2a, alpha Leu-3a, OKT1, OKT3, OKT4, OKT6, OKT8, W6/32, 26/114, DA-2, 2DI, J5, AN51 and OKT9 together with conventional surface marking by rosetting (E, Fc gamma, Fc mu, C3b, C3d) and staining for surface and cytoplasmic immunoglobulin (SIg, CyIg) heavy and light chain classes. The results confirm the reproductability and specificity of staining with monoclonal antibodies against T cells and T cells subsets. Evidence is presented for reactivity of alpha Leu-I antibody with SIg positive and Ia positive cells in some lymphomas (centroblastic centrocytic, lymphocytic and immunoblastic), and 2 cases showed evidence of marking with OKT3 on SIg positive cells in T cell predominant immunoblastic lymphoma. Lymphoblastic lymphomas of T cell type expressed the marker OKT6. On the basis of these results criteria for the diagnosis of T cell lymphoma are suggested. The monoclonal antibody J5, reactive with C-ALL antigen, showed variable positivity, occasionally strong in B cells in cases of centroblastic and centrocytic follicular lymphoma. Proportions of cells staining with the monoclonal antibody OKT9 showed a correlation between levels of cellular expression of transferrin (trf) receptor and the histological grade of malignancy, OKT9+ cells being elevated in high grade lymphomas, and in some cases of transforming lymphoma of low grade histological class. These results are discussed and indicate the advantage of employing a wide range of defined monoclonal reagents in the phenotypic evaluation of NHL.

Adolescent↗

Centrocytic lymphoma: a distinct clinicopathologic and immunologic entity. A multiparameter study of 18 cases at diagnosis and relapse.

The clinical, pathologic, and immunologic aspects of malignant lymphoma of centrocytic type (ML,cc) were studied at diagnosis and often at relapse in 18 patients. The typical patient was a middle-aged or older man with adenopathy, often massive splenomegaly, hepatomegaly, marrow involvement, and, not infrequently, peripheral blood involvement. Histopathologically, ML,cc had a diffuse or vaguely nodular growth pattern with, predominantly, cells resembling centrocytes (cleaved follicular center cells) sometimes with admixed small round lymphocytes but with virtually no transformed cells. In 2 cases the neoplastic cells formed a mantle zone around reactive-appearing follicles. Cell suspensions and frozen sections revealed the monoclonal B-cell nature of all but 1 nonmarking case, and the polyclonality of the follicles in the 1 mantle zone case tested. The B cells had some, but not all, characteristics of both normal mantle and follicular center cells when eight nodes were studied with the use of a panel of monoclonal antibodies, peanut lectin, and endogenous alkaline phosphatase activity. Of 13 patients who underwent repeat biopsies, 1 developed a high grade unclassifiable B-cell lymphoma, and 6 had less marked changes. None of 7 patients tested had a change in light chain class. In conclusion, ML,cc is a distinct entity separable from other B-cell lymphomas in which either centrocytes or small round lymphocytes predominate.

Adult↗

Slow cirrhosis--or no cirrhosis? a lesion causing benign intrahepatic portal hypertension.

We report the histological findings in livers from a group of 60 patients with benign intrahepatic portal hypertension. The lesion is benign in comparison with true cirrhosis in the sense that most of the patients survive many years from the time of diagnosis. The histological changes, in our view, differ from those of any variant of cirrhosis and generally do not progress even after many years. The essential features are: (1) irregular capsular thickening; (2) thickening of some portal tracts with fine fibrous septa radiating out from some of them; and (3) distortion of lobular architecture with hyperplastic expansion of some areas and compression of others and irregularly distributed central veins. We suggest that this is the lesion responsible for at least some cases of so-called idiopathic non-cirrhotic portal hypertension.

Follow-Up Studies↗

Posttreatment laparotomy as a guide to management in patients with Hodgkin's disease.

Staging laparotomy and splenectomy were performed on 46 adult patients after combination chemotherapy for advanced Hodgkin's disease (HD). There was no preoperative evidence of intra-abdominal disease in 32 patients, 27 of whom were in complete clinical remission, while five had only residual mediastinal abnormalities. In the remaining 14 patients, there was clinical suspicion of active HD. Histologically abnormal tissue was obtained from 19 of 46 (41%) operations. Active abdominal HD was detected in six of 46 patients (13%) or in six of 19 patients having previous evidence of intra-abdominal disease (31%). The spleen was involved in all patients, and in two of these patients there was evidence of both active and ablated disease. Pathologic evidence of ablated HD was detected in 13 patients. The prediction of active intra-abdominal HD, by lymphography or by computerized tomographic scanning, following mustine, vinblastine, procarbazine, and prednisolone therapy, was frequently inaccurate. There was no operative mortality. Morbidity was similar to that of pretreatment laparotomy. At a median followup of 26.5 months (range 5-59), 39 of 40 patients with no evidence of active abdominal HD remain in continuous remission. The contribution of posttreatment laparotomy toward the management of patients with HD is discussed.

Adolescent↗

The use of four-drug combination chemotherapy (D.A.V.E.) in the treatment of advanced Wilms' tumour.

A study was begun in 1971 at St. Bartholomew's Hospital with a combination of 4 drugs, dactinomycin (actinomycin D), adriamycin, vincristine and Endoxan (cyclophosphamide) (D.A.V.E.), together with surgery and radiation, in the treatment of stage III and stage IV Wilms' tumour. Seventy-one percent of the children treated achieved complete response. The median survival from diagnosis was 19 months, and in those children achieving complete response the median disease-free survival has not yet been reached. Toxicity was not a serious problem. The study group is compared with a group of children treated at this hospital before 1971. There is an improved survival in the children treated with D.A.V.E. Children who have relapsed with stage I or stage II disease may also respond. This four-drug combination was well tolerated and effective, and confirms recent experience suggesting that intensive multiple-drug regimens may be curative even in advanced disease.

Adolescent↗

Non-cirrhotic intrahepatic portal hypertension: A long term follow-up study.

The clinico-pathological features and prognosis of 59 cases of non-cirrhotic portal hypertension seen at one hospital over a 30-year period are described. Diagnosis was made on operative wedge liver biopsy in most cases. All but two had clinical features of portal hypertension and 47 had bled from oesophageal varices. In 53, portal decompression was performed without operative death or variceal rebleeding. Subsequent liver histology in 16 cases up to 18 years after diagnosis showed no change in the majority. The relatively static morphology was reflected in the clinical course. Twenty-two patients have died but only 11 as a result of liver disease or its treatment. Actuarial analysis shows the five year survival to be 90 per cent and the 30-year survival 55 per cent in strong contrast to the grim prognosis for cirrhosis. The infrequency of operative liver biopsies and unfamiliarity with the disease lead to underdiagnosis.

Adolescent↗

Liver damage in children with acute leukaemia and non-Hodgkin's lymphoma on oral maintenance chemotherapy.

Eight of 36 children receiving maintenance chemotherapy for acute lymphoblastic leukaemia or non-Hodgkin's lymphoma had liver biopsies on the basis of clinical abnormalities and/or elevated serum enzyme levels. Six biopsies were abnormal, including one in a boy with spider naevi who showed micronudular cirrhosis; he appeared to retain methotrexate in the blood for a prolonged period and his SGOT level did not return to normal for 19 months after maintenance chemotherapy was discontinued. The five other abnormal biopsies showed minor changes in the portal tracts. The six children with abnormal liver histology showed a wide variation in their early handling of an oral methotrexate dose. There was a statistically significant rise in mean SGOT and alkaline phosphatase during treatment, but the wide scatter in values precluded their use as accurate indicators of liver damage in these children.

Adolescent↗

Immuno-histological diagnosis of lymphoproliferative diseases by selected combinations of antisera and monoclonal antibodies.

Tissue sections of frozen biopsy specimens obtained from normal and hyperplastic human lymphoid tissues, 33 cases of non-Hodgkin lymphomas as well as various forms of immunoregulatory disorders (angioimmunoblastic and dermatopathic lymphadenopathy) were analysed in immunofluorescence tests (using red TRITC and green FITC double-labelling). A panel of antisera including well-characterized conventional reagents to immunoglobulin classes, T lymphoid and Ia-like antigens, and monoclonal antibodies was used. In selected cases the results were compared with the observations of membrane-marker staining on viable cells in suspension. the findings show that the immunological methods can give a very accurate analysis of the normal and malignant lymphoid cells, and can provide complementary information to conventional histology. The investigator can choose the reagent combinations which give answers to various specific questions: e.g. antisera to light chains establish the monoclonality of lymphomas, whilst staining combinations for human T and Ia-like antigens are particularly useful in various immunoregulatory disorders. Monoclonal antibodies will be particularly useful in various immunoregulatory disorders. Monoclonal antibodies will be particularly useful reagents for analysing the tissue distribution of lymphoid subpopulations and ancillary cells in tissue biopsy specimens.

B-Lymphocytes↗

Pituitary and testicular fibrosis in association with retroperitoneal fibrosis.

A patient is discussed who originally presented with retroperitoneal fibrosis, and subsequently developed both pituitary fibrosis and testicular fibrosis. Replacement of testicular tissue by fibrosis has not previously been described in this condition, while we have only been able to find a single previous report of pituitary fibrosis. Fibrous replacement of testis and pituitary should be considered as a further manifestation of the midline fibrosing syndrome.

Adult↗