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Biomedical subjects

T L Smith

Publications and source records attributed to T L Smith.

At least 19 recordsLinked to original sources

Postoperative adjuvant chemotherapy with fluorouracil, doxorubicin, cyclophosphamide, and BCG vaccine. A follow-up report.

Two hundred twenty-two patients with stage II or III breast cancer following regional therapy were treated with a combination of fluorouracil, doxorubicin hydrochloride (Adrimycin), cyclophosphamide, and BCG vaccine. At 54 months of study (median follow-up, 30 months), the estimated proportions remaining disease-free two and three years after surgery were 83%and 78%, respectively, in the chemotherapy group and 64% and 55%, respectively, in 151 historical control patients. Estimated two- and three-year survival rates were 93% and 89%, respectively, in the chemotherapy group and 84% and 58%, respectively, in the control patients. Congestive heart failure has developed in three patients, possibly related to the use of doxorubicin. Adjuvant chemotherapy with these drugs was effective in prolonging the disease-free interval and survival of patients irrespective of menopausal status, degree of nodal involvement, or stage of the disease.

Antineoplastic Agents

Adjuvant chemoimmunotherapy following regional therapy for isolated recurrences of breast cancer (stage IV NED).

A combination of 5-fluorouracil, Adriamycin, cyclophosphamide, and BCG (FAC-BCG) was evaluated as adjuvant treatment in breast cancer patients following surgical excision and/or radiation of first site of recurrent disease. In a group of 68 patients treated with FAC-BCG, the estimated proportion remaining free of disease at 2 years from first recurrence was 69%, compared to 24% in 60 historical control patients (P less than 0.01). Estimated 2-year survival rate from first recurrence was 85% for the FAC-BCG patients and 78% for the controls (P = 0.07). This regimen has significantly prolonged the disease-free interval from the first recurrence, but additional follow-up is needed to determine its effect on long-term survival.

Antineoplastic Agents

Necrotizing colitis in patients with cancer.

Necrotizing lesions of the colon occur in patients with malignancy. We identified 26 patients with cancer (23 with acute leukemia and three with solid tumors) who died from necrotizing colitis. Autopsies revealed three pathologic categories: pseudomembranous colitis in 69 per cent, agranulocytic colitis in 19 per cent and ischemic colitis in 12 per cent. Most died from sepsis. A comparison of characteristics was made with a control population matched for diagnosis, age, cause of death and duration of neoplasia. Nearly all patients in both groups had fever and were granulocytopenic secondary to chemotherapy. Most received antineoplastic and antimicrobial regimens during the month prior to their terminal illness. Abdominal pain and distention, stomatitis and necrotizing pharyngitis were frequently associated with colitis. Hyperbilirubinemia was a frequent late complication in those with colitis and the control group. Single and multiorganism septicemia were found more frequently in patients with colitis. As antemortem diagnosis was unusual, aggressive attempts at diagnosis are necessary to assess the true incidence of this disorder and the best therapy.

Adolescent

Effects of chromatic targets on a throwing task for subjects referred for learning disability.

The purpose of the study was to determine the effects of chromatic and achromatic targets on performing a throwing task for subjects referred for learning disability. 20 boys referred to the Perceptual Motor Development Center practiced under achromatic or chromatic target conditions. After 5 practice bouts, each subject immediately performed on the opposite condition. When subjects were aware of chromatic and achromatic target alternatives, chromatic targets facilitated performance.

Child

Complete remissions in metastatic breast cancer treated with combination drug therapy.

One hundred sixteen patients with metastatic breast cancer who achieved complete remission with combination chemotherapy were analyzed to ascertain the factors that affect the duration of complete remission and the patterns of relapse. The median duration of complete remission was 17 months. Disease recurred in 81 patients (70%) at periods ranging from 3 to 44 months after achievement of complete remission. The duration of complete remission was inversely related to the bulk of metastatic tumor. Twenty-three patients treated with combined oophorectomy and chemotherapy experienced the longest remissions (median duration of 33 months); only eight (35%) of them have relapsed. Seventy-six percent of the relapses occurred in previously known sites of tumor involvement; most of the remainder involved the brain. The short duration of complete remissions and tendency to relapse in sites of initial involvement suggest that patients with metastatic breast cancer who achieved complete remission with combination chemotherapy still had substantial residual tumor. Consolidation treatments, using hormonal therapy and non-cross-resistant chemotherapy along with irradiation to initial sites of metastases, whould be investigated to ascertain their usefulness in prolonging the remissions.

Adult

Central nervous system relapse in malignant lymphomas: risk factors and implications for prophylaxis.

The records of 292 patients with malignant lymphoma other than Hodgkin's disease, registered in our protocols from 1967 to 1977, were reviewed to identify those with central nervous system (CNS) involvement. Thirty-one patients were encountered with this complication, an incidence of 11%. Patients with a diffuse histology had a higher frequency of CNS recurences (27/174 = 16%) in contrast to only 4/118 (3%) for those with nodular types. However, if only patients with diffuse histology in CR are considered, the frequency of CNS relapse is 13.5% (13/98). The risk factors that predict for the development of this complication were studied using multivariate analysis. Diffuse poorly differentiated lymphocytic and diffuse undifferentiated lymphomas were found to be associated with a high risk of CNS relapse. Prior chemotherapy, bone marrow involvement, age less than 35, and extranodal disease were also identified as high-risk factors. Using the information generated by a logistic regression model, patients with malignant lymphoma of diffuse type can be classified into three categories when first seen: low-risk group, intermediate, and high-risk group. CNS prophylaxis is recommended for the intermediate and high-risk group, while only close follow-up is advised for the low-risk group patients who have one adverse characteristic.

Adult

Chemotherapy of acute leukemia: a comparison of vincristine, cytarabine, and prednisone alone and in combination with cyclophosphamide or daunorubicin.

Adults (274) with acute leukemia (AML) were randomly assigned to one of three treatment regimens: vincristine, prednisone, cytarabine--(1) 100 mg/sq m/day with cyclophosphamide (COAP); (2) 100 mg/sq m/day with daunorubicin (DOAP); and 200 mg/sq m/day (OAP). Cytarabine was infused continuously for five days. Patients entering complete remission randomly received maintenance treatment with COAP or OAP. For 197 previously untreated AML patients given COAP, DOAP, or OAP, remission rates were 37%, 35%, and 43%, respectively; median lengths, 40, 45, and 90 weeks; median survival, 7, 11, and 8 weeks. No statistically significant difference was found among treatments. Therefore, adding cyclophosphamide or daunorubicin, or using the COAP regimen with continuously infused cytarabine, produced no significant improvement over previously reported regimens. There was no significant difference in remission lengths in previously untreated AML patients maintained on OAP (median 81 weeks) or COAP (median 65 weeks).

Acute Disease

Intensive postoperative chemoimmunotherapy for patients with stage II and stage III breast cancer.

For the past 34 months, a combination of 5-fluorouracil, adriamycin, cyclophosphamide, and BCG (FAC-BCG) was evaluated as adjuvant treatment in stage II and III breast cancer patients with positive axillary nodes. In the group of 131 patients receiving FAC-BCG, the estimated proportion remaining disease-free at 2 years from surgery was 91% compared to an estimated 69% in a group of 151 historical control patients (p less than .01). This advantage was statistically significant in all subgroups except for patients with primary tumor less than 3 cm and for patients with less than 4 positive nodes. Estimated 2-year survival rates were 9,6% for FAC-BCG patients and 86% for control (p = .02). Treatment was well tolerated. Adjuvant FAC-BCG seems effective in prolonging disease-free interval and early survival in patients with stage II and III breast cancer. Its long term efficacy will require longer follow-ups.

Adult

Sterol requirement of Mycoplasma capricolum.

Mycoplasmas require an external source of sterol for growth. For Mycoplasma capricolum this requirement is met not only by cholesterol but also by the methylcholestane derivatives lanosterol, cycloartenol, 4,4-dimethylcholesterol, and 4beta-methylcholestanol. Cholesteryl methyl ether and 3alpha-methylcholestanol serve equally well as sterol supplements. None of the growth-supporting sterol derivatives tested was metabolically modified. The unusual acceptance of diverse cholestane derivatives by a mycoplasma species contrasts with the structural attributes thought to be necessary for sterol function in eukaryotic membranes.

Cholestanes

Randomized trial of protected environment--prophylactic antibiotics in 145 adults with acute leukemia.

One hundred and forty-five adults with acute leukemia were randomized to receive remission induction therapy in or out of a protected environment (PE) with prophylactic antibiotics orally (PA) or systemically (SA). Sixty-three patients were randomized in PE and 82 outside a PE. The proportion of patients who survived long enough to receive an adequate trial was higher in the PE (97%) than out (82%) (P = .01). The complete remission (CR) rate was 71% in and 43% out of the PE (P less than .01). Fifty-five patients received PA and 90 received SA. The CR rates were 61% and 45%, respectively. Of the 145 patients, 73 (50%) developed 102 episodes of major infections. Twenty-six of 63 patients in the PE developed major infection compared to 47 of 82 outside a PE (P = .08). The incidence rate of 13% fatal infections in a PE was significantly smaller than the 28% rate outside a PE (P = .04). The number of days with infections at less than 500 neutrophils/mm3 was also significantly lower inside a PE than outside (P less than .01). When comparing patients receiving SA or PA, there was no statistically significant difference in the incidence of infections. Forty-one patients received OAP Chemotherapy and 104 received adriamycin-OAP plus BCG. The CR rate on OAP was 44% compared with 60% on Ad-OAP + BCG. Infection rates were 76% and 40%, respectively (P less than .01). The median survival time was 72 weeks for patients in PE compared with 42 weeks for patients outside a PE (P less than .01). The prophylactic antibiotic regimens were well tolerated by most patients. This prospective randomized study has demonstrated statistically significant advantages for a lowered risk of fatal infection, higher CR rate and longer survival of patients treated in a PE with prophylactic antibiotics compared with patients treated in a conventional hospital room. Also, there was evidence for the superiority of adriamycin-OAP + BCG treatment compared with OAP.

Acute Disease

Factors predicting for response and survival in adults with advanced non-Hodgkin's lymphoma.

Knowledge of the prognostic factors that characterize a disease can assist in planning and analyzing clinical trials. The present study was conducted to determine the characteristics related to response and survival in patients with stage III and IV non-Hodgkin's lymphoma who were treated with combinations of cyclophosphamide, vincristine sulfate, and prednisone. Considering each characteristic individually and using stepwise regression analysis, tumor bulkiness, prior therapy, sex, and pretreatment lymphocyte count were selected as the four most important prognostic variables. Tumor architecture (diffuse or nodular pattern) and cell type, hemoglobin level, and symptoms although not important in predicting response were found to be important in predicting survival. The hemoglobin level had only marginal importance in predicting response. Factors found not be important were age, stage, symptoms, cell type, nodularity, marrow involvement, prior extensive radiotherapy, and bone involvement. A logistic regression equation has been derived that can be used to predict response rate.

Cyclophosphamide

Survival with inoperable lung cancer: an integration of prognostic variables based on simple clinical criteria.

The objectives are to identify and integrate through regression analysis those fundamental clinical variables predicting survival of patients with inoperable lung cancer managed in a modern setting. Median survival time from first treatment in 129 patients with limited disease and 187 patients with extensive disease was 36 and 14 weeks, respectively. Within the proposed survival model for limited disease, weight loss was the major prognosticator followed by symptom status, supraclavicular metastases, and age. Within extensive disease, symptom status and age were dominant variables followed by weight loss and metastases to liver, opposite hemithorax, brain, and bone. Survival by cell type was similar within the limited and extensive disease groups. The data identify the essential factors which must be controlled or accounted for in studies analyzing survival as a dependent variable.

Age Factors

A study of intermittent alternating drug program reinduction therapy on the frequency and duration of response in adult acute leukemia.

Of 41 adults with a diagnosis of acute leukemia that were randomized for induction therapy in combination with methotrexate, 6-MP, vincristine and prednisone (POMP) versus a combination of cytosine arabinoside, cytoxan, vincristine and prednisone (COAP), 23 (56%) patients achieved a complete remission. During remission, patients received consolidation therapy with the three courses of remission induction regimen that they had not received initially. They then received daunomycin (three courses) and L-asparaginase and were then maintained for two years with their induction therapy. The median duration of survival for all patients was 40 weeks; the median duration of survival of those patients that responded to chemotherapy was 80 weeks. There was no significant difference between the two induction regimens with regard to complete remission more than four and one half years from diagnosis and two and one half years from discontinuation of all therapy.

Acute Disease