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Biomedical subjects

J R Durant

Publications and source records attributed to J R Durant.

At least 55 records · Page 3Linked to original sources

Assessment of myeloma maintenance regimen of prednisone. Adriamycin, imuran, and vincristine in a murine plasmacytoma model.

A current southeastern cancer study group protocol for the treatment of multiple myeloma involves induction with BCNU, cyclophosphamide, and prednisone (BCP) and maintenance with either melphalan and prednisone (MP), prednisone, Adriamycin, imuran, and vincristine (PAIV), or delayed treatment of relapsed cases following induction. These combinations of drugs are used as induction regimens to establish their chemotherapeutic effects and hematological toxicity in the murine MOPC 104E plasmacytoma model. The three combinations of drugs produce rapid, reliable, and reproducible tumor regressions. However, MP is the only combination which consistently gives long-term disease-free survivors. This particular regimen has least toxicity and is considered to be most effective. BCP produces complete remission with no relapses; however, long-term survivors are not observed with this combination due to early deaths because of drug toxicity. Most of the mice on the PAIV regimen die due to drug toxicity. This combination is considered least effective. With the different drug regimens, toxic events and regressions are noted to occur at different time periods, indicating that perhaps tumor cells in different stages are being destroyed. Toxic events as measured by hematocrit and body weight changes always precede regression by several days. This disparity between rapid drug effects on the host and a delayed effect on the tumor remains unexplained but may possibly be used to advantage in designing future trials.

Animals↗

Comparison of steroid receptor levels in renal-cell carcinoma and autologous normal kidney.

Since a number of renal-cell carcinomas regress with hormonal manipulation, we have identified and measured the levels of estrogen, progestin and glucocorticoid receptors in 47 autologous pairs of normal and neoplastic kidney tissues. High-affinity receptors for these hormones were detected in kidney tissues of both sexes by means of a dextran-coated charcoal assay. Glucocorticoid receptors were demonstrated in renal cancer tissues for the first time, and were higher in the tumor (mean 31.3 +/- SEM 5.6) than in the normal tissue (mean 18.5 +/- 3.1 fmol/mg cytosol protein). There was a significant difference in the quantities of progestin receptors (expressed as fmol/mg cytosol protein) in normal (mean 18.4 +/- SEM 3.3) versus neoplastic (mean 10.4 +/- SEM 4.0) kidney specimens (p less than 0.007). There was a significant difference between the binding affinity of the progestin receptor in the male tumors (Kd = 2.2 +/- SEM 0.9 nM, n = 10) and that of the females, (Kd = 9.3 +/- SEM 6.5 nM) (p less than 0.04). When an affinity of less than 9.9 X 10(-9) M and greater than 10 fmol/mg cytosol protein were used as criteria for classifying a tissue as positive for progestin receptors, only 17% of tumors contained these receptors while 45% of normal tissues exhibited them. According to these criteria, no differences were observed in the frequency of occurrence of either estrogen receptors or glucocorticoid receptors in tumor versus normal kidney. Data from this study suggest that the use of endocrine therapy should be re-examined in the treatment of renal-cell carcinoma.

Adenocarcinoma↗

Provoked priapism in sickle cell anemia.

Two patients with sickle cell anemia are reported who developed relative impotence after repeated episodes of priapism. They learned that excessive ethanol ingestion produced an erection and utilized this mechanism to satisfy sexual partners. Hospitalization and transfusion therapy were required for repeated episodes of priapism. Extensive interviews were required in order to learn the sequence of events. This synergistic relationship between ethanol and priapism should be sought in patients with repeated hospitalizations for this complication of sickle cell anemia because it is preventable with appropriate counseling.

Adult↗

Isolated chylopericardium associated with lymphoma.

We have described the occurrence of isolated chylopericardium associated with lymphocytic lymphoma in remission. The effusion may have been related to previous mediastinal lymphoma. Further, pericardial and mediastinal exploration for pericardial effusion represents appropriate treatment of patients with malignancies in whom preliminary studies fail to demonstrate conclusive evidence of residual neoplasm.

Chyle↗

A murine plasmacytoma model for screening active drugs for human myeloma.

The basic problem of current animal models is the inability to select and rate the relative effectiveness of new drugs of myeloma of man. As a first step in broaching this problem, results of clinical drug trial studies were used for predicting activity of the drugs in the MOPC 104E plasmacytoma model. Comparison of the model with human myeloma and six additional murine plasmacytomas for drug response indicates close correlation between the reported results in man and the expected results in the animal models. The MOPC 104E model was versatile because drug effects could be rapidly measured in vivo in individual animals. The effect of the drug on the rate of growth, the rate of regression, the doubling time, the number of tumor cells killed, and the tumor and drug toxicities on the host could be continuously measured. These measurements were used to select active drugs and to rate the relative activity of the different drugs for myeloma.

Animals↗

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.

Carcinoma, Squamous Cell↗

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.

Adult↗

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.

Adenocarcinoma↗

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.

Adolescent↗

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.

Chemotaxis↗

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%).

Diagnostic Errors↗