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Biomedical subjects

R L Stephens

Publications and source records attributed to R L Stephens.

At least 109 records · Page 6Linked to original sources

m-AMSA and adenocarcinoma of the endometrium. A Southwest Oncology Group study.

Twenty-eight patients with advanced or recurrent adenocarcinoma of the endometrium were treated with m-AMSA. Twenty-four patients (86%) were treated at 30 mg/M2/d X 3d q 21 d and four patients were treated at 40 mg/M2/d X 3d q 21 d intravenously. Eighty-eight courses of m-AMSA were administered with a median of 2 courses per patient. One (5%) complete response occurred in 19 patients evaluable for response. Toxicity was well tolerated and generally mild. m-AMSA may be relatively inactive in the treatment of advanced adenocarcinoma of the endometrium; further studies, however, are required to determine its effectiveness in primary previously untreated disease.

Adenocarcinoma↗

Long-term survival and toxicity in small cell lung cancer. Southwest Oncology Group study.

In the first study of combined chemotherapy and radiation therapy for small cell lung cancer by the Southwest Oncology Group, 17 patients survived more than five years after treatment was initiated (4.6 percent). Late relapse, or a second primary malignancy three to six years after diagnosis, accounted for death in five of these patients. Late recurrences involved the chest, bone, and liver; none occurred in the central nervous system. Disease-free survival continues in 10 patients (6 percent of those with limited disease and 1 percent of those with extensive-stage diseases) at a minimal follow-up in excess of six years. One definite case of chronic treatment-related toxicity occurred: congestive cardiomyopathy after 450 mg/m2 of doxorubicin, successfully managed with digitalis and diuretics. One severe neurologic problem (orthostatic hypotension with preterminal dementia) and two less severe neurologic complications (occasional falling episodes without documented cause and cerebrovascular accident) may be treatment-related. Progressive pulmonary disability, post-herpetic pain syndromes, organic brain syndrome, and hematologic abnormalities have not been observed to date. Nitrosourea administration and/or co-administration of a nitrosourea or methotrexate during the induction phase of treatment with radiotherapy to the brain may account for the higher incidence of complications observed by others in long-term survivors.

Antineoplastic Combined Chemotherapy Protocols↗

Vindesine in patients with metastatic malignant melanoma: a Southwest Oncology Group study.

A phase II study using vindesine (3 mg/m2 by slow intravenous push at seven to 14 day intervals) was carried out in 42 patients with metastatic melanoma. There was one complete remission (2.5%) of greater than 12 months duration; seven partial remissions (17.5%) of two, three, three, four, five, six and eight months duration; 11 with no change (27.5%) of one to 10 months duration; and 21 (52.5%) patients with increasing disease. Toxicity included neutropenia, neurotoxicity, phlebitis and cellulitis at the site of injection, alopecia, fever and chills, myalgias, and gastrointestinal toxicity. It was concluded that vindesine does have activity in some patients with metastatic malignant melanoma. Further studies in previously untreated patients are warranted.

Adult↗

Improved complete remission rates and survival for patients with large cell lymphoma treated with chemoimmunotherapy. A Southwest Oncology Group Study.

Between 1974 and 1977, 652 patients with non-Hodgkin's lymphoma without prior chemotherapy were randomized to 1 of 3 combination chemotherapy programs designed to induce complete remission (CR): COP-bleomycin (180 patients), CHOP-bleomycin (232 patients) or CHOP plus immunotherapy with Bacillus Calmette Guerin (BCG) (240 patients). With mature follow-up, the major effect of BCG immunotherapy was observed in patients with large cell lymphomas (diffuse or nodular "histiocytic") and not in other common lymphoma subtypes. CR rate for 65 patients with large cell lymphoma treated with CHOP-BCG was 68% compared to 48% in 61 patients treated with CHOP-bleomycin (P = 0.02) (two-tailed test) or 44% for 45 patients treated with COP-bleomycin (P = 0.02). CR duration for both CHOP-based regimens was similar and superior to that produced by COP-bleomycin (P = 0.03). Survival of patients with large cell lymphoma treated with CHOP-BCG was better than that observed with CHOP-bleomycin (P = 0.02) or COP-Bleomycin (P = 0.002). Although the explanation for the favorable effect of BCG remains unclear, further clinical trials to evaluate the combination of chemotherapy and other "biologic response modifiers" is warranted for patients with lymphoma.

Antineoplastic Agents↗

Vindesine in head and neck cancer. A Southwest Oncology Group Phase II pilot study.

Vindesine was tested in 23 fully evaluable patients with advanced carcinomas of the head and neck. All had received previous chemotherapy. No complete or partial responses resulted after one or more courses of 1.5 mg/m2 i.v. bolus daily X 2 days. Leukopenia was noted in 46% and peripheral neuropathy was reported in 29%. This dose-schedule of vindesine is inactive in previously treated patients with squamous carcinomas of the head and neck.

Antineoplastic Agents↗

Adjuvant therapy of breast cancer: the Southwest Oncology Group experience.

The Southwest Oncology Group in a prospective randomized study compared one year of adjuvant combination chemotherapy with continuous CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone) to two years of intermittent L-phenylalanine mustard (L-PAM) in women with operable breast cancer with histologically positive axillary lymph nodes. In fully and partially evaluable patients with a 68-month median follow-up, treatment failures have occurred in 27% of 172 receiving CMFVP and 47% of 186 women given L-PAM (p = 0.002). The advantage for women receiving CMFVP was seen for all subsets regardless of menopausal status except among women who were premenopausal and had 1-3 positive nodes. Based on this study, a second study was implemented using both the estrogen-receptor (ER) content of the primary tumor and axillary nodal status to select therapy.

Antineoplastic Combined Chemotherapy Protocols↗

The nature of the Ln3+-angiotensin II complex. A 13C nmr study of the binding of Yb3+ to angiotensin II.

The nature of the Yb3+-angiotensin II complex is examined by 13C nuclear magnetic resonance. The ytterbium-induced shifts of most resonances are observed to be strongly dependent on pD, while a few are observed to be largely independent of pD. These observations are shown to be consistent with stepwise binding of the lanthanide ion to the carboxylates of aspartic acid and the C-terminus.

Angiotensin II↗

Choriocarcinoma, thyrotoxicosis, and the Klinefelter syndrome.

A patient with the combined features of Klinefelter syndrome, thyrotoxicosis and a primary mediastinal choriocarcinoma is reported. Review of the literature reveals that extragonadal germ cell tumors appear to be significantly associated with the Klinefelter syndrome. The reason for this is presently unclear but may involve an unusual propensity of the extragonadal aneuploid germ cell to undergo malignant degeneration.

Adult↗

Effect of mannitol and plasma on the cytotoxicity of cisplatin.

A soft agar cell culture for human granulocyte precursor cells (CFU-c) was used to assess the cytotoxic effect of cisplatin before and after preincubating the drug with either mannitol and/or fresh human plasma. Consistent growth inhibition of CFU-c was found with survival of 87, 64 and 34% at cisplatin concentrations of 10(-7) M, 10(-6) M and 10(-5) M respectively. Dose-related survival was not changed by preincubating cisplatin with mannitol in molar ratios of 1:100 and 1:1000 for 4 and 24 hr. Preincubating 10(-5) M cisplatin with human plasma increased CFU-c survival corresponding to a loss of activity of 92 and 98% after 4- and 24-hr preincubations respectively. No significant difference in survival of CFU-c was noted whether bone marrow cells were exposed to cisplatin in human plasma or in the ultrafiltrate of human plasma. Mannitol did not change the decrease in cisplatin activity due to plasma protein binding. These data indicate that the cytotoxic effect of cisplatin can be reduced by exposure to human plasma but not to mannitol.

Adult↗

The Southwest Oncology Group experience: adjuvant therapy for stage IB and II non-seminomatous testicular cancer.

During a two year period, 65 patients with Stage II non-seminomatous testis cancer were randomized to receive adjuvant chemotherapy and radiation. Of the 52 evaluable patients, 23 received radiation followed by chemotherapy (sequential), and 29 received the same chemotherapy as initial treatment, but had drug treatment temporarily interrupted for radiation (sandwich). The combined treatment was well tolerated, but did not eliminate recurrence. With regard to duration of survival and disease-free survival, no statistically significant difference could be found between the sequential and sandwich approaches.

Adult↗

NMR studies of the variant-3 neurotoxin from Centruroides sculpturatus Ewing.

We report a preliminary high-resolution proton nuclear magnetic resonance characterization of the variant-3 toxin from the scorpion Centruroides sculpturatus Ewing (range Southwestern USA). This toxin assumes a well defined folded conformation in aqueous solutions at room temperature and undergoes reversible thermal denaturation. A number of amide hydrogens exhibit exchange life times varying from several minutes to several hours. A few tentative assignments of the low field aromatic CH resonances has been made on the basis of 2D-COSY and NOE experiments. The upfield shifts exhibited by Trp-47 suggest a unique microenvironment for this residue. The NMR data suggest that there is some degree of correlation between the solution structure of the variant-3 toxin and its crystallographic structure. Our studies provide a basis for a detailed elucidation of the structure-function relationships of these interesting scorpion toxins which bind to the sodium channels of excitable membranes and delay sodium current inactivation.

Amino Acid Sequence↗

Adriamycin versus adriamycin plus cis-diamminedichloroplatinum (DDP) in advanced transitional cell bladder carcinoma. A Southwest Oncology Group study.

Patients with advanced transitional cell bladder carcinoma were randomized to receive either adriamycin alone, or adriamycin plus DDP. Overall response (CR + PR) was 8/41 (19%) for adriamycin alone versus 16/37 (43%) for the combination (p = 0.02). Median response duration was 14 weeks for adriamycin versus 25 weeks for the combination (p = 0.17). Median survival was 28 weeks on adriamycin versus 31 weeks on the combination (p = 0.82). Median survival of responders was 43 weeks, and for patients with stable disease it was 29 weeks. This was significantly better than for those with increasing disease at 15 weeks (p = 0.02). Increased frequency of leukopenia and gastrointestinal toxicity were seen with the combination. Cardiotoxicity and nephrotoxicity were not prohibitive.

Carcinoma, Transitional Cell↗

Gallium nitrate in malignant lymphoma: a Southwest Oncology Group study.

Gallium nitrate was evaluated by the Southwest Oncology Group in 38 patients with malignant lymphoma, both Hodgkin's disease and non-Hodgkin's lymphoma. Treatment was administered every 2 weeks at a dose of 700 mg/m2, with acceptable toxicity. Seven partial responses (18%) with a duration of 3-11 months were seen: one of seven in Hodgkin's disease and six of 26 in diffuse non-Hodgkin's lymphoma. No responses were noted in nodular types. Gallium nitrate has activity in lymphomas and should be combined with more active drugs for patients who have undergone less intensive prior therapy.

Adolescent↗

Geomelophagia. An unusual pica in iron-deficiency anemia.

A patient with lung cancer treated by radiation and in remission presented with a two-month history of compulsive eating of raw, chilled potatoes. Suspicion of a pica due to iron-deficiency anemia was confirmed after complete laboratory evaluation. The source of iron loss was found to be gastrointestinal bleeding. Therapy with iron sulfate was begun, with a subsequent increase in the hemoglobin level; the pica ceased within one week of initiation of therapy. If searched for, pica is a common manifestation of iron deficiency; however, this patient apparently represents the first report of geomelophagia. Appropriate investigation of compulsive eating habits might lead to the diagnosis of iron deficiency and also allay patients' anxieties toward their behavior.

Aged↗