Biomedical subjects
J R Durant
Publications and source records attributed to J R Durant.
Overview. Current status of clinical trials.
The five areas outlined in this discussion represent a large proportion of the current environment for clinical trials. They identify significant obstacles to the advancement of knowledge in clinical oncology. There is no single or overriding solution to the health care system and its problems with funding and access or to the antiintellectual mood of our times. Continuous efforts to improve science are needed now more than ever. Adequate accession to trials is an ongoing issue. These problems are compounded by the ethical issues created by today's opportunities. The etiquette of territoriality is no less daunting. Each of these affects the environment in which trials are conducted, and each deserves the serious attention of all of us. Some suggestions for action have been made. The need for resolution is obvious.
How to organize a multidisciplinary clinic for the management of breast cancer.
It is the opinion of this essayist that the advantages to the patient and the clinician of a multidisciplinary clinic far outweight the modest loss of autonomy and the need for commitment of additional time in order to make such a clinic function effectively. It is hoped that the success of this issue of the Surgical Clinics of North America and the serious application of the principles outlined in it will encourage the creation of many such successful clinics.
The public understanding of science.
Explore the source record for details and available documents.
Immunotherapy of cancer: the end of the beginning?
Explore the source record for details and available documents.
Analysis with antiidiotype antibody of a patient with chronic lymphocytic leukemia and a large cell lymphoma (Richter's syndrome).
A murine monoclonal antibody made against an idiotypic determinant (Id) of surface IgM/IgD lambda molecules on chronic lymphocytic leukemia (CLL) cells of a 71-year-old woman was used for clonal analysis by two-color immunofluorescence. The anti-Id antibody identified IgM+/IgD+/lambda+ B cells as the predominant cell type of her CLL clone. In addition, substantial proportions of the IgG and IgA B cells and most of the IgM plasma cells in her bone marrow and blood were Id+. Six years after diagnosis, the patient died of respiratory failure due to infiltration of lungs by malignant cells. Autopsy revealed a dramatic change in the tumor cell morphology. The lungs, hilar nodes, and liver were infiltrated by a diffuse large cell lymphoma admixed with the leukemic cells. By immunohistologic staining these anaplastic lymphoma cells were IgM+/IgD-/lambda+ B cells expressing the same Id noted earlier on the CLL cells. The immunoglobulin gene rearrangement pattern on Southern blot analysis was also the same in leukemic blood cells and in the tissues involved by the lymphoma. Thus, the combination of antiidiotype and immunoglobulin gene analyses in this patient with Richter's syndrome revealed that a CLL clone, seemingly "frozen" in differentiation, was actually undergoing isotype switching, differentiation into plasma cells, and evolution into a rapidly growing and fetal lymphoma.
ASCO--as a young adult.
Explore the source record for details and available documents.
Tumor burden, chemotherapy, and cell kill in osteosarcoma model.
The complex relationships among tumor cell burden, dose and schedule of chemotherapy, and efficacy were investigated in a murine osteosarcoma model in which an easily measured marker provided an accurate, dynamic estimate of host tumor cell burden. Cytoxan (200 mg/kg) produced a 93.2-99.997% tumor cell kill in animals with a pretreatment tumor burden of 0.6-3% body weight. In animals with a pretreatment tumor burden of 5.1-10.24% body weight, however, the same dose of cytoxan produced less than 1 order of magnitude tumor cell kill (31-71%). A schedule utilizing three doses q12 days in animals with a moderate burden of tumor (up to 5% body weight) produced a cell kill of six or more orders of magnitude with some cures, an event which was more frequent with added immunostimulation. A schedule utilizing two doses q20 days in animals with a larger body burden (5-10% of body weight) was essentially ineffective. These results suggest that a small initial body burden (low stage) and an aggressive schedule of treatment are necessary for optimum results in cancer treatment. Small delays in initiation of treatment and prolonged intervals between doses can convert an effective drug to an ineffective one without the need to invoke biochemical mechanisms of resistance.
Unusual manifestations of non-Hodgkin's lymphoma.
Two patients with biopsy proven lymphomatous infiltration of uncommon sites are presented. One had histiocytic lymphoma, involving the true vocal cord with a squamous cell carcinoma on the opposite vocal cord. The other had diffuse well-differentiated lymphocytic lymphoma, presenting with nodal and periorbital disease. After local radiation therapy and while clinically free of other lesions, he developed hemotochezia due to several polypoid lesions throughout the entire colon and prostatic infiltration with symptoms of lower urinary tract obstruction. Both problems were solved after specific treatment.
The superiority of combination chemotherapy over single agent chemotherapy in small cell lung carcinoma.
From June 1974 to October 1976, 288 patients with small cell undifferentiated lung carcinoma were entered into a randomized, controlled study comparing the two noncycle-active induction regimens of cyclophosphamide vs. the combination of cyclophosphamide, doxorubicin and imidazole carboximide (DTIC). Patients were stratified by extent of disease, previous radiotherapy and performance status. Responding patients and those who did not progress were then randomized to receive their initial regimen alone, or their initial regimen with added cycle-active therapy (vincristine, hydroxyurea and methotrexate). While only 4/34 (12%) evaluable patients treated with cyclophosphamide achieved a response (greater than 50% regression), a final total of 119/217 (57%) evaluable patients on the three drugs have responded (p = 0.005). The survival curve for all the combination-treated patients was significantly better than for those treated with cyclophosphamide alone (p = 0.012). There was no demonstrable statistical superiority in length of remission or survival for patients on the combination who received in addition cycle-active consolidation therapy. In the combination chemotherapy group, survival duration was longer for patients with limited disease than extensive disease (p = 0.035). There was a strong correlation between quality of remission produced by the combination and survival.
Urinary hexosaminidase in patients with lung carcinoma.
The specific activity of urinary hexosaminidase was determined in 58 patients with various histological types of lung carcinoma. Compared to an apparently healthy control population, 32/35 patients with widely disseminated disease showed elevated values and 18/23 patients with disease confined to the chest had normal hexosaminidase values. Detailed studies of 18 patients indicated that declining hexosaminidase values were associated with effective therapy, rising values generally accompanied progressive disease.
Pulmonary toxicity associated with bischloroethylnitrosourea (BCNU).
Ten patients developed pulmonary fibrosis after bischloroethylnitrosourea (BCNU) therapy for malignancy. This was lethal in seven patients, four of whom had no evidence of tumor at autopsy. Presenting symptoms were either the insidious onset of cough and dyspnea or the sudden onset of respiratory failure. Physical findings were unremarkable. Chest roentgenogram usually showed interstitial infiltrates. Pulmonary function studies showed resting hypoxia with diffusion and restrictive defects. This complication of therapy does not appear to be dose related and may be made more likely by the concomitant administration of cyclophosphamide. Prednisone therapy did not benefit most patients. The literature and the implications of the use of BCNU alone or in combination are reviewed.
Combination chemotherapy with intermittent 1-3-bis(2-chloroethyl)1-nitrosourea (BCNU), cyclophosphamide, and prednisone for multiple myeloma.
Explore the source record for details and available documents.
BCNU, velban, cyclophosphamide, procarbazine, and prednisone (BVCPP) in advanced Hodgkin's disease.
Explore the source record for details and available documents.
Mucosal eosinophilic gastroenteritis with systemic involvement.
The unusual features in a 46 year old white woman with mucosal eosinophilic gastroenteritis are described. In addition to involvement of the gastrointestinal tract, she had eosinophilic splenitis and hepatitis. She responded to corticosteroid therapy, but not to an elimination diet or to cromolyn sodium therapy. The possible role of various factors chemotactic for eosinophilia in the patient are reviewed, and the place of the disorder among the hypereosinophilic syndromes is discussed.
The accuracy of retroperitoneal ultrasonography in Hodgkin's disease and non-Hodgkin's lymphoma.
Three hundred and thirty-six B-mode ultrasound examinations of the retroperitoneal region were performed on 179 patients with Hodgkin's disease or non-Hodgkin's lymphoma; histological confirmation was available in 56 patients. Ultrasonography was correct in predicting retroperitoneal periaortic lymph node involvement in 87.5% of cases. Node size was correctly predicted 98.2% of the time, and nodes 2 cm or larger in diameter were detectable. Ultrasound was more accurate than physical examination, and as accurate as gallium-67 imaging and lymphography in disease detection. The combination of ultrasound and gallium imaging gave the best accuracy of detection (97%).
BCNU with and without cyclophosphamide, vincristine, and prednisone (COP) and cycle-active therapy in non-Hodgkin's lymphoma.
Two hundred and ninety-eight evaluable patients with non-Hodgkin's lymphoma were stratified according to histology, treated with either BCNU, cyclophosphamide, Oncovin (vincristine), and prednisone (BCOP) or cyclophosphamide, Oncovin (vincristine), and prednisone (COP), and evaluated at 3 months. Those with a good partial (PR) or complete response (CR) were then separated and randomized to be treated with either cycle-active therapy (methotrexate, cytosine arabinoside, and 6-thioguanine) or more induction therapy with COP or BCOP. Patients not achieving a good PR at 3 months received cycle-active therapy. The results indicate (a) that there is a significant advantage for good over poor histologies with regard to good PRs at 3 months; (b) that the addition of cycle-active therapy (as administered in this study) is of advantage when the tumor has been significantly reduced only for patients receiving COP induction; and (c) that BCOP has an advantage over COP in diffuse histiocytic lymphoma where the percentage of CRs, their durability, and subsequent survival are superior for patients treated with BCOP. Since this lymphoma accounts for about 25% of all non-Hodgkin's lymphoma patients, this regimen represents a useful tool for the chemotherapist.
Demonstration of Cryptococcus neoformans in a stained bone marrow specimen.
Disseminated cryptococcosis is seen with increased frequency in patients with malignant hematologic disease. Usually the diagnosis rests on spinal fluid studies, and little attention has been paid to the direct examination of a bone marrow specimen. A febrile woman with an advanced histiocytic lymphoma was intensively treated with antineoplastic agents; the antemortem diagnosis of cryptococcosis was suspected from direct examination of the bone marrow and was subsequently confirmed by culture. Visualization of fungi in special stained bone marrow specimens could be useful in the initial examination of febrile patients with neoplastic diseases and/or compromised host defenses, and would permit early institution of specific therapy.