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Biomedical subjects

D C Tormey

Publications and source records attributed to D C Tormey.

177 records · Page 10Linked to original sources
PubMed1967

Quantitative studies of phytohemagglutinin-induced DNA and RNA synthesis in normal and agammaglobulinemic leukocytes.

Leukocytes from nine patients with acquired agammaglobulinemia were studied in vitro. Synthesis of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) induced by phytohemagglutinin was measured by determination of the degree of incorporation of labeled precursor. Synthesis of both DNA and RNA was decreased in the agammaglobulinemic cells. The presence of an inhibitor in the patients' sera could not be demonstrated. These results suggest that the basic defect in agammaglobulinemia is cellular rather than humoral.

Agammaglobulinemia↗
PubMedDate not supplied

Urinary excretion of polyamines by patients with advanced malignancy.

Levels of putrescrine, spermidine, and spermine in urine were determined by means of a sensitive ion-exchange chromatographic method in patients with advanced solid tumor malignancies, in patients with diseases other than cancer, and in normal control subjects. Elevation above 2 SDS of the normal mean were found in varying number of patients in each tumor category. For those malignancies studied that involved more than 20 patients, the greatest incidences of increased excretion were 66% for spermine in patients with colon carcinoma and 50% for putrescine and spermidine in patients with bronchogenic carcinoma. The highest levels and greatest frequency of elevated polyamine levels were found in patients with Burkitt's lymphoma, and changes in clinical tumor status associated with treatment appeared to correlate well with polyamine levels in this disease. Abnormal amounts of polyamines were also excreted by some patients with diseases other than cancer, indicating that increased polyamine excretion is not restricted or specific to the neoplastic state. It was also found that the levels of polyamines were apparently not affected by the intake of meat or the diet eaten, and remained in a rather narrow excretion range for any one individual at different time intervals. This study was carried out as part of a program to determine and evaluate biologic materials present in body fluids that may be used to follow and evaluate response or progression of neoplastic disease in patients during treatment regimens. The results suggest that abnormal urinary polyamine levels may be characteristic of neoplastic growth for some patients with malignant disease. Further studies are necessary to determine if these compounds may be helpful in assessing disease status for patients with such solid tumor malignancies as colon and bronchogenic carcinoma although their potential as useful "biologic markers" appears less promising than originally anticipated.

Adult↗
PubMedDate not supplied

Mitomycin and tamoxifen versus mitolactol, doxorubicin, and tamoxifen in patients with previously treated breast cancer.

One hundred thirty patients with previously treated advanced breast cancer were treated in a cooperative trial to investigate the effect of mitomycin plus tamoxifen (MT) and to compare its relative value to combination therapy with mitolactol, doxorubicin (ADM), and tamoxifen. An additional 76 patients who had had prior exposure to ADM were randomized to receive MT or MT plus fluoxymesterone. MT versus mitolactol, ADM, and tamoxifen was not significantly different in efficacy; however, there were significant differences in toxicity. This study showed that MT is an effective and acceptable second-line treatment for advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Phase I study of vinblastine and verapamil given by concurrent iv infusion.

Overcoming resistance to chemotherapy is an important goal in cancer treatment. In many systems, resistance to anthracyclines and vinca alkaloids correlates with a diminished intracellular content of drug. In P388 leukemia and Ehrlich ascites tumor, an active outward transport of anthracyclines and vinca alkaloids occurs. Calcium channel blockers, such as verapamil, inhibit this active outward transport and increase intracellular content of vinblastine and anthracyclines in cells resistant to vinca alkaloids and anthracyclines, respectively. We report a phase I trial of vinblastine (1.5 mg/m2 daily as iv continuous infusion X 5 days) in 17 patients and concurrent verapamil in escalating doses. Verapamil was administered as a loading dose (0.02-0.1 mg/kg) followed by a maintenance infusion (0.036-0.18 mg/kg/hour) for 5 1/2 days with continuous cardiac monitoring. There was no apparent augmentation of vinblastine toxicity when vinblastine and verapamil were given concurrently. ECG change was the dose-limiting toxicity. At 0.12 mg/kg/hour, five of nine patients developed first-degree heart block (mean P-R interval, 0.32 seconds; range, 0.23-0.52 seconds). Junctional rhythms were noted in two of 17 patients. Reversible nonspecific T-wave changes were seen in four of 17 patients. Blood pressure and left ventricular ejection fractions (ultrasonic) were not altered. Five of 17 patients had wbc count nadirs less than 2000/mm3, and two of 17 patients had platelet count nadirs less than 100,000/mm3. Four patients experienced neurotoxicity. A mean vinblastine concentration of 2.2 ng/ml (0.55 nM) and a mean verapamil concentration of 290 ng/ml (0.45 microM) were achieved with the concurrent 5-day infusion. The tolerable levels of verapamil obtained appear to be less than those which were reported to inhibit vinblastine efflux in vitro. Additional in vitro experiments at the tolerable doses of vinblastine and verapamil are recommended.

Adult↗
PubMedDate not supplied

Phase I trial and pharmacokinetics of acivicin administered by 72-hour infusion.

Acivicin, an L-glutamine antagonist, was administered to 37 evaluable patients with refractory advanced solid tumors in a phase I trial. A total of 67 evaluable 72-hr iv infusions were given at 3- to 4-week intervals. Doses ranged from 3.0 to 90 mg/m2/course. Reversible CNS toxicity was dose-limiting and included lethargy, somnolence, anxiety, hallucinations, and paranoid psychoses. Four of five patients experienced unacceptable CNS toxicity at 90 mg/m2. Three of eight patients experienced reversible diaphoresis and chills without fever at 75 mg/m2, and two had dizziness and ataxia. Hematopoietic toxicity, nausea, emesis, and diarrhea were mild and dose-related. One patient developed a blue-green discoloration of the infusion arm. Serial plasma and urine specimens from 13 patients were assayed for acivicin using a microbiologic method. Peak plasma levels at the end of the 72-hr infusions correlated with dose and ranged from 0.09 to 1.10 microgram/ml. When data from six patients were fitted to a two-compartment open model, alpha-half-life ranged from 1.1 to 63 mins, while beta-half-life ranged fro 338 to 629 mins. Renal clearance ranged from 6 to 24 mL/min, and nonrenal clearance accounted for 58%-83% of the total drug clearance. CNS toxicity correlated with plasma acivicin levels which exceeded 0.9 microgram/ml for greater than 16 hrs, but not with peak plasma levels or with the integrals of the concentration x time curves. Minor responses were seen in one patient with melanoma, in one with epidermoid pulmonary carcinoma, and in two with colon carcinoma. A starting dose of 60 mg/m2/course was recommended for phase II trials, with possible escalation to 75 mg/m2 in the second course if the drug was well-tolerated.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Venous thrombosis during multimodal treatment of primary breast carcinoma.

In a cooperative group study of 433 breast cancer patients treated with 2 years of postmastectomy chemotherapy, 22 (5%) developed venous thromboses of various types. Two patients died. None of the patients had demonstrable tumor metastases at the time of the venous thrombosis, although seven had metastases a median of 11 months after the thromboses. Thirteen living patients have not had tumor recurrences. No patient developed thrombosis after the chemotherapy was completed. It is possible that one or more of the chemotherapeutic agents initiated the clotting problems. Thrombophlebitis is a possible problem occurring during adjuvant chemotherapy for breast cancer and requires prompt treatment.

Aged↗