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Biomedical subjects

J Blom

Publications and source records attributed to J Blom.

At least 127 records · Page 7Linked to original sources

Long term follow-up of combination chemotherapy-radiotherapy of stage III Hodgkin's disease: a Cancer and Acute Leukemia Group B study.

The Cancer and Acute Leukemia Group B studied the effect of combination chemotherapy-radiotherapy on Stage III Hodgkin's disease. Chemotherapy consisting of 4 weekly doses of vinblastine and one dose of mechlorethamine hydrochloride was followed by no therapy (CT), radiation to involved fields (CTIF) or total nodal radiation (CTTN). Two other treatment arms included total nodal radiation alone (TN) or total nodal radiation followed by chemotherapy (TNCT). Maximum follow-up is ten years. Complete remission percentages were 36 (8/22) for CT, 71 (17/24) for CTIF, 100 (21/21) for CTTN, 86 (19/22) for TNCT and 89 (16/18) for TN. Disease-free survival in patients receiving radiation +/- chemotherapy is 23% (19/73) at 5 years, but even after 9 years relapses were observed in two patients. Forty-one percent of all patients are alive and 32% have survived for five years. Ability to administer adequate therapy was the main determined for response duration and survival. Factors influencing the outcome of the disease include histology, age, splenectomy, initial white blood cell count and performance status, whereas symptomatology, initial absolute lymphocyte count and sex played no role on survival.

Adult↗

A modified assay for studies of cultured granulocyte precursors: cryopreservation of stimulating mononuclear cells.

Mononuclear cells (MNC), isolated from peripheral blood of healthy donors, were cryoprotected by dimethyl sulfoxide and stored in liquid nitrogen. Colony-stimulating factor (CSF), produced by cryopreserved MNC, was compared with that of nonfrozen controls in a double-layer agar system with human bone marrow as target cells. Our results indicate that cryopreserved MNC retain their ability to stimulate myelopoiesis-committed stem cells after freezing. In addition, evidence was obtained that CSF of feeder layers changes, depending on the duration of preincubation and cell concentration. In a system where either stimulating or target cells are cryopreserved the dynamics of interactions between normal or abnormal cell lines can thus be studied.

Blood Preservation↗

Multiple myeloma resistant to melphalan: treatment with cyclophosphamide, prednisone, and BCNU.

Eighty-nine patients with multiple myeloma resistant to melphalan were randomized to receive cyclophosphamide plus prednisone (CP) (47 patients) or cyclophosphamide plus BCNU plus prednisone (CBP) (42 patients). No differences were detected in the two groups prior to therapy. Objective responses occurred in three (7%) of the CP patients and in seven (17%) of the CBP patients. About 40% of the patients in each group achieved some response. Toxic reactions consisted mainly of leukopenia and thrombocytopenia. Median survival was not different in the two groups. The median survival time was 31 months among those patients with an objective response and 9.4 months among those without an objective response. The addition of BCNU to CP increased the frequency of objective response, but not significantly. This triple combination (CBP) cannot be recommended.

Carmustine↗

A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy.

A prospective randomized trial was conducted comparing the clinical response of 78 previously untreated patients with advanced metastatic breast cancer to a combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or to a combination of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF). Sixty-two percent of the patients receiving CMF responded to treatment compared to an 82% response rate for the patients receiving CAF. Although within acceptable limits, hematologic and GI toxicity was greater with CAF. There was no significant difference in the duration of response to the two regimens. Therefore, the therapeutic difference between the two therapies is a higher initial response rate to the adriamycin containing regimen.

Breast Neoplasms↗

Adult acute leukemia: frequency of central system involvement in long term survivors.

The incidence and frequency of CNS relapses in long term surviving adults, age eighteen and over, covering the period 1967-1972, were presented. Four of 20 patients with ANLL and 12 of 24 patients with ALL were demonstrated to have CNS leukemia during the course of their illness. The onset of neurologic manifestation in three of four ANLL patients with CNS leukemia was observed within three months of the diagnosis, whereas it was delayed to 6-12 months interval in eight of 12 ALL patients. CNS relapses, a major determinant for CNS prophylactic and maintenance therapy, were observed in 75% of the patients with ALL and none in ANLL patients who were treated with I.T. chemotherapy and cranial radiation of 2000 R. Therefore, our observation suggests that CNS prophylactic and maintenance therapy should be of value in adults with ALL as in children; whereas, in ANLL, further observation is warranted before any definite therapy can be advocated.

Adolescent↗

The ultrastructure of macrophages found in contact with plasma cells in the bone marrow of patients with multiple myeloma.

The ultrastructure of a macrophage found in the bone marrow of 15 patients with multiple myeloma is described. The macrophage is designated the dendritic bone marrow macrophage, due to the various branching cell forms in which it can be found. It is further distinguished by having contact with plasma cells. At the contact zones a thickening of the inner leaflet of the cytoplasmic membrane of the plasma cells is observed, whereas no morphological changes are present in the adjoining membranes of the macrophage. These macrophages show a great variation in their phagocytic capacity, and only few show morphological evidence of being actively phagocytic. A few dendritic bone marrow macrophages show a localized thickening of the inner leaflet of their cytoplasmic membrane, but this thickening is never found in the regions of contact with plasma cells.

Bone Marrow↗

The ultrastructure of contact zones between plasma cells and macrophages in the bone marrow of patients with multiple myeloma.

The ultrastructure of intercellular connections between plasma cells and dendritic bone marrow macrophages found in bone marrow aspirations from 15 patients with multiple myeloma is described. Two types of cell-to-cell contact were observed: 1) a juxtaposed type and 2) a mortise-joint type. In both types the zones are characterized by an amorphous electron dense layer adherent to the inner leaflet of the cytoplasmic membrane of the plasma cell, whereas no morphological changes are present in the macrophage. The thickness of the electron dense layer in the plasma cell was found to range from 11 to 33 nm and its extension along the membrane fron 0.2 micronm to 2--3 micronm. The distance from plasma cell surface to the surface of the macrophage was found to range from 11 to 27 nm, but the two cell membranes were always parallel at the contact zone region. At the contact zones small amounts of electron dense material were generally present in the interspace between the cells, and sometimes fine bridges of this material were seen to connect the two cells. The cytoplasm of the plasma cell was sparse in organelles at the contact zone region except for cytoplasmic filaments (7--9 nm in diameter). However, more than 50 per cent of the plasma cells did show a few electron dense, membrane-bound granules close to the contact zones. In some plasma cells a few coated vesicles were also found adjacent to the dense layers of the contact zones.

Bone Marrow↗

Electron microscopy of lymph nodes of hamsters experimentally infected with Treponema pertenue.

The morphology of lymph node tissue from normal hamsters and from hamsters experimentally infected with Treponema pertenue Gauthier was compared by means of light and electron microscopy. The capsules of the lymph nodes from infected hamsters showed an increased thickness in comparison with those of the non-infected animals. The infected lymph nodes differed from normal lymph nodes by small accumulations of neutrophilic leucocytes in the cortical areas. In addition, the amount of intercellular collagenous matrix present between large elongated cells was greatly increased in lymph nodes from infected animals. Electron microscopy of thin sections of infected lymph nodes showed intercellularly located treponemes in the leucocyte infiltration areas. These regions also showed the increased amounts of the collagenous matrix. Treponemes were occasionally found intracellularly in macrophages. These treponemes did not show their typically helical shape, but were present as spherical forms or cysts.

Animals↗

Second malignancies in patients with multiple myeloma.

Seven patients with multiple myeloma who developed a second neoplasm are presented. There were four patients with acute leukemia and three patients with non-hematologic neoplasms. The patients with acute leukemia were among the longest survivors (median duration approximately 72 months) and the response to anti-leukemic therapy in these patients was generally poor. Of the three patients with non=hematologic neoplasms, one patient was observed with simultaneous renal cell carcinoma and the other two patients developed adenocarcinoma of the colon and lung subsequently. In addition, two patients with mammary carcinoma who subsequently developed multiple myeloma were included. Literature was reviewed and the possibility that multiple myeloma itself might be a risk factor for the development of other malignancies was discussed.

Adenocarcinoma↗

Evaluation of adriamycin and dibromodulcitol in metastatic breast carcinoma.

A phase 1 to 2 evaluation of a combination of adriamycin (ADR) and dibromodulcitol (DBD) was performed in patients with progressive, metastatic breast carcinoma. All but one patient had been treated previously with chemotherapy. ADR was given on Day 1 or Days 1 and 8, and DBD was given on Days 1 to 10 of each 21- to 28-day treatment cycle. Side effects were evaluable in 54 patients, and 50 patients were evaluable for therapeutic response. The dose-limiting toxicities were leukopenia and thrombocytopenia. The severity of both toxicities increased as both the ADR and DBD doses increased; however, the effect of increases in DBD dose was much more profound. The mean white blood cell count and platelet nadirs occurred, respectively, on Days 15.3 and 15.9; both nadirs were delayed for 0.6 day by each 30-mg/sq m/day increase in the DBD dose and delayed for 1.7 to 3.9 days using the Day 1, 8 rather than the Day 1 ADR schedule Recovery of the peripheral counts by Day 29 was prolonged by the Day 1, 8 ADR schedule and by increasing the DBD dose. A tolerable dose schedule for previously treated patients was considered to be ADR, 40 mg/sq m on Day 1, and DBD, 135 mg/sq m on Days 1 to 10 repeated every 28 days. Responses were observed in 46% (23 of 50) of the patients. There were 1 complete remission, 19 partial remissions, and 3 improvements. Thirteen patients showed no change and 14 developed progressive disease. There were responses in 13 of 37 (36%) with visceral dominant disease as compared to 7 of 8 (87%) with osseous and 3 of 5 (60%) with soft tissue-dominant disease. There were 22 of 48 (46%) responses in patients previously exposed to alkylating agent therapy. Twnety-two patients had responded and 19 had failed to respond to prior alkylating agent-containing regimens; the response rates to DBD in these groups were respectively, 45 and 42%. The median time to remission was 29 days. The median time to therapeutic failure was 5.1 months for responders, 2.3 months for patients with no change, and 29 days for progressors. The combination of ADR and DBD appears to be an active and well-tolerated program in patients with previously treated metastatic breast carcinoma.

Adult↗

Immunological monitoring and immunotherapy in carcinoma of the lung.

One hundred and seven patients with carcinoma of the lung underwent immunologic testing, and 62 of these patients were randomized to an immunotherapy protocol comparing the effects of Pasteur strain BCG, either alone or combined with allogeneic tumor cells, to the effects of no immunotherapy. Patients with residual disease left at the time of surgery or with metastatic disease at the time of diagnosis showed no increase in survival as a result of this form of immunotherapy. An insufficient number of patients with less advanced disease, in whom we would expect the most beneficial effect, have been entered in this study. In general, we were unable to document substantial effects of immunotherapy on the immunologic parameters tested. Only in recall antigen skin testing was there a statistically significant increase in reactivity in the immunotherapy groups. Tests of general immune status appeared to have a predictive value in monitoring lung cancer patients. Anergic patients had a poorer prognosis than did patients who demonstrated skin test reactivity. Patients with normal percentages of lymphocytes (T cells) forming rosettes with sheep erythrocytes at 29 degrees C were generally normal in other tests of immune competence. In serial studies of rosette formation, all patients who developed recurrent disease had a pattern of depressed or falling rosette values, and these abnormalities occurred an average of 3.1 months prior to clinical detection of recurrence. Patients with large-cell anaplastic carcinoma were found to have a significantly higher incidence of depressed rosette levels than the other histologic types. Both large and small-cell anaplastic patients had significantly depressed lymphocyte proliferation by mitogens and allogeneic cells. Although lung cancer patients have been described as immunologically depressed, they are capable of recognizing tumor-associated antigens. When tested in leukocyte migration inhibition assays with tumor-associated antigens, the majority of the patients in our study were found to be reactive. The use of a 3 M KCl extract of pleural effusion cells from a patient with pulmonary adenocarcinoma has given good reactivity and specificity in lung cancer patients of all histologic types. In addition, these patients have been shown to respond in a mixed lymphocyte/tumor interaction to tumor-associated antigens (Dean, 1976b).

Adenocarcinoma↗

Adult central nervous system leukemia: incidence and clinicopathologic features.

Two hundred and seventy-two adults diagnosed between 1949 and 1971 as having acute leukemia were evaluated. Two hundred and fifty-seven patients had died and autopsies were obtained in 202 cases. Central nervous system (CNS) leukemia was demonstrated in 22 of 93 autopsies with acute nonlymphocytic leukemia (ANLL) during the period 1949 through 1966 and 8 of 47 during the period 1967 through 1971. Nine of 45 autopsies on acute lymphoblastic leukemia (ALL) patients diagnosed during 1949 through 1966 had CNS involvement, compared to 7 of 17 during 1967 through 1971. The median time from diagnosis of acute leukemia to CNS manifestations was two months for ANLL and six months for ALL. Headache, papilledema, and cranial nerve palsy were the common findings with meningeal leukemia. Early CNS involvement was observed in patients with high initial leukocyte/blast counts, low platelet counts, and early lymphadenopathy and hepatosplenomegaly. Ten of 13 patients treated between 1967 and 1971 with cranial irradiation and intrathecal chemotherapy responded; however, the duration of remission in ALL was short-lived with subsequent relapses at various intervals. In contrast, CNS recurrence in ANLL was rare. The value of CNS prophylactic and maintenance therapy is discussed.

Adolescent↗

A study of Russell bodies in human monoclonal plasma cells by means of immunofluorescence and electron microscopy.

Five patients with a serum M component were shown to possess plasma cells containing Russell bodies. Four of the patients suffered from multiple myeloma, whereas the fifth probably had a different disease or was in a premyeloma stage. The Russell bodies stained blue with the May-Grünwald-Giemsa stain and were found both in the nuclei and in the cytoplasm of the plasma cells. Ultrastructural studies showed that the Russell bodies were osmophilic and those located in the cytoplasm were always situated within the cisternae of the rough endoplasmic reticulum. The intranuclear Russell bodies were always surrounded by a triple layered membrane, and some evidence was obtained that these bodies were first formed within the perinuclear space of the cells. Immunofluorescence studies using anti-L chain conjugates showed a positive marginate straining of the intranuclear as well as the cytoplasmic Russell bodies of the cells from all patients. Only one patient had cells with Russell bodies which also stained their location in the plasma cells. It is concluded that some plasma cells in multiple myeloma may produce an excessive amount of L chains which, in combination with a failure in the secretion of immunoglobulin molecules, may lead to the formation of Russell bodies.

Adult↗