Search PubMed⌕ Search

Biomedical subjects

D R White

Publications and source records attributed to D R White.

At least 19 recordsLinked to original sources
PubMed1992

A phase I-II study of recombinant intrapleural alpha interferon in malignant pleural effusions.

Malignant pleural effusion is a common and significant source of morbidity for many patients with cancer. In an attempt to control this condition without using chest tube drainage, we administered recombinant interferon alpha-2b (INTRON, Schering-Plough, Kenilworth, NJ) intrapleurally via catheter after routine thoracentesis. Twenty-two installations of interferon were administered to 15 patients in incremental dosages of 3-50 x 10(6) U/m2. Of 20 evaluable treatments, six (30%) achieved effusion stabilization; there were no complete or partial responses. Only one of nine treatments at a dosage less than 20 x 10(6) units/m2 resulted in symptoms, while four of 11 treatments at the higher dosage were associated with transient fever, chills, and chest pain. Interferon demonstrated no major activity in this heavily treated patient population with advanced malignancy.

Adult↗
PubMed1991

Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. The Piedmont Oncology Association.

BACKGROUND: Chemotherapy for metastatic breast cancer is palliative, and the optimal duration of therapy is unknown. We designed a trial to determine whether continuous treatment is superior to stopping treatment after a brief induction period and resuming treatment when the disease progresses. METHODS: We treated 250 women with metastatic breast cancer with six courses of cyclophosphamide, doxorubicin, and fluorouracil given every three weeks. At the completion of this induction period, women whose disease either regressed or remained stable were randomly assigned to receive either continued treatment with cyclophosphamide, methotrexate, and fluorouracil (maintenance therapy) or no further treatment (observation) followed by treatment with cyclophosphamide, methotrexate, and fluorouracil when disease progression became evident (reinduction). RESULTS: The combined rate of complete and partial responses after initial therapy was 30 percent (71 of 233 patients who could be evaluated; 95 percent confidence interval, 25 percent to 37 percent). In another 42 percent (98 patients), the disease remained stable. A total of 145 patients were randomized. Seventy-one were randomly assigned to the maintenance-therapy group, and 74 to the observation group. The median time to progression was 9.4 months for patients in the maintenance-therapy group and 3.2 months for patients in the observation group (P less than 0.001). After reinduction therapy, the median time to progression was 3.5 months. The median length of survival from the time of initial therapy was 14.8 months for all 250 patients; it was 21.1 months for the 71 patients in the maintenance-therapy group and 19.6 months for the 74 patients in the observation group (P = 0.67). Maintenance therapy was the most important determinant of the time before progression (P less than 0.001), but it was not associated with prolonged survival. The changes in performance status were similar in the patients in both groups, but nausea, vomiting, and mucositis were significantly more frequent in the maintenance-therapy group. CONCLUSIONS: In patients with breast cancer who received induction chemotherapy for 18 weeks, subsequent continuous chemotherapy was associated with a significant prolongation of the time before progression as compared with those receiving no further therapy; overall survival, however, was not significantly different in the two groups.

Adult↗
PubMed1991

A randomized trial of chemotherapy (L-PAM vs CMF) and irradiation for node positive breast cancer. Eleven year follow-up of a Piedmont Oncology Association trial.

158 evaluable patients with stage II, lymph node positive, carcinoma of the breast were randomized to adjuvant therapy with either melphalan (L-PAM) or cyclophosphamide, methotrexate, and fluorouracil (CMF) after mastectomy. In addition, patients were randomized to be treated with or without post-operative irradiation therapy (RT) in addition to their chemotherapy. At a median follow-up time of 11 years, there is no difference in time to relapse (P = 0.69) or survival (P = 0.55) among the four treatment groups. Multivariate analysis including treatment arm, age, race, tumor size, histologic type, performance status, time to onset of treatment, menopausal status, and number of positive nodes, revealed that only the number of positive nodes (less than 4 vs greater than or equal to 4) was related to disease-free and overall survival. Ten year relapse-free survival for patients with less than 4 positive nodes compared to those with greater than or equal to 4 positive nodes was 63% versus 30%, and overall survival 63% versus 41%, respectively. Patients who received post-operative radiation therapy had significantly less local recurrence than those treated with chemotherapy alone (P = 0.03) but without improvement in relapse-free or overall survival. In this trial, post-operative radiation therapy when added to chemotherapy decreased the risk of local recurrence without adverse effects on survival. Treatment outcome was not influenced by chemotherapy regimen, but differences may have been obscured by the small sample size.

Adult↗
PubMed1991

The composition of body tissues (II). Fetus to young adult.

The composition of body tissues is a function of the age, nutrition, state of health and physical activity of the individual. In this paper, the effects of age on the composition of healthy tissues are reviewed. Eleven soft tissues (adipose tissue, blood--whole, brain--whole, heart, kidney, liver, lung, muscle--skeletal, placenta, skin and spleen) and cortical bone are considered. Elemental compositions, mass and electron densities are tabulated for the tissues, as a function of age, from fetus to young adult. Although the compositions given here are predominantly for healthy tissues, reported changes because of dietary influences are briefly discussed.

Adolescent↗
PubMed1991

Gender differences in categorizing adolescents' weight status.

Categorization of normal or overweight status, using percent overweight and visual inspection, showed good agreement for 51 adolescent girls, but not 70 boys. Only 49% of boys with high relative weights were seen as overweight compared to 90% of girls.

Adolescent↗
PubMed1990

A phase II trial of high-dose cytarabine and cisplatin in previously untreated non-small cell carcinoma of the lung. A Piedmont Oncology Association Study.

Thirty-seven chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC) were treated with cytarabine (3 g/m2 intravenously [IV] during 3 hours) after IV bolus cisplatin (100 mg/m2 repeated every 3 weeks). Aside from nausea and vomiting, the principal toxicity was hematologic, with Grade IV myelosuppression in 32% and Grade III in 14%. Four patients died while on study. One complete and four partial responses were observed for an overall response rate of 14%. Responses were limited to lymph node and lung metastases and occurred in two of 17 adenocarcinomas, two of 12 squamous cell carcinomas, and one of eight large cell carcinomas. At this dose, the plasma level of cisplatin is only 3 micrograms/ml and the plasma level of cytarabine is 10 to 50 micrograms/ml, compared with the levels of 10 micrograms/ml and 1000 micrograms/ml, respectively, required for in vitro synergy. The severity of myelotoxicity observed indicates that, even at these levels, cisplatin enhances cytarabine activity. The combination may prove useful in malignancies that are sensitive to cytarabine, but is not of benefit in cytarabine-resistant malignancies such as NSCLC.

Adult↗
PubMed1990

Combination high-dose etoposide and vincristine infusion.

Following the identification of a synergistic antitumor effect in a murine model, the combination of etoposide and vincristine has been explored in the clinic. Etoposide was given at 4 dose levels (250, 500, 750 or 1,000 mg/m2) with each dose given in 3 equal fractions daily for 3 days. The dose of vincristine was fixed (two 0.75 mg infusions over 22 hours each between doses of etoposide). A total of 26 patients were entered into study and 7, 11, 10 and 5 patients were treated at the 250, 500, 750, and 1,000 mg/m2 dose levels, respectively. Myelosuppression was the principle side effect and Grade 4 WBC toxicity (less than 1,000/mm3) developed in 14%, 27%, 40% and 40%, respectively, of the patients treated at each of these respective dose levels. Life-threatening infections occurred in 0%, 9%, 30% and 60% of the patients at these levels, respectively. Reversal of marrow toxicity was rapid with repeat courses given at 3-week intervals. Non-hematologic toxicity, including neurotoxicity, nausea, vomiting, and mucositis was generally mild when present. Objective responses were observed in 1 patient each with refractory Hodgkin's disease and immunoblastic lymphoma. Prolonged periods of stable disease occurred in 2 patients with adenocarcinoma of the lung and one patient with Hodgkin's disease. The starting dose of etoposide recommended for further trials of this agent in combination with infusion of vincristine is 500 mg/m2 given in fractionated doses; dose escalation should be possible in many patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

A phase II trial of PEG-L-asparaginase in the treatment of non-Hodgkins lymphoma.

A polyethylene glycol conjugate of L-asparaginase (PEGLA) was administered to 21 patients with refractory non-Hodgkin's lymphoma. The dose given was 2,000 mu/m2 intramuscularly every 2 weeks. Eligibility required at least one prior trial of chemotherapy and ambulatory performance status. At entry, all patients had measurable lesions and documented disease progression. The median age of the patients was 61 years; 18 (86%) were ambulatory with minimal symptoms, 12 patients (57%) had 3 or more prior regimens, and 13 (62%) had stage IV disease. Histologic subtype was low grade in 11 patients (52%), intermediate in 7 (33%), high grade in 2 (10%) and unclassifiable in one (5%). There were two partial responses (11%) noted (95% confidence interval of response of 1-30%). Eleven patients (52%) were removed from study due to disease progression. Nine patients (43%), required removal for toxicity (7 for protracted nausea and vomiting and 2 for confusion). One patient died of sepsis while on study but this was not considered drug related. Almost one third of patients complained of fatigue or loss of appetite. Nausea and vomiting occurred in approximately half the patients and was moderate to severe in 9. Diarrhea and abdominal pain were also noted in one-third of those treated. Changes in the partial thromboplastin time and fibrinogen were noted in most patients but resulted in no bleeding complications. In this trial, PEGLA displayed modest activity in a heterogenous group of patients with progressive non-Hodgkin's lymphoma.

Adult↗
PubMed1990

Factors affecting the acrosome reaction in human spermatozoa.

Large pieces of human cumulus oophorus were exposed for 20-30 min to washed spermatozoa or to spermatozoa recovered after a swim-up procedure, and then fixed for electron microscopy. Spermatozoa of both populations penetrated deeply into the cumulus within that time, and none of 48 observed clearly had undergone an acrosome reaction (AR). As measured by fluorescence microscopy, an AR rate of 12% in spermatozoa obtained at 4 h following a swim-up increased to about 25% in samples incubated in culture dishes for approximately 20 h. However, this latter AR rate was no different in the presence or absence of a cumulus/oocyte complex, and was only moderately greater in 50% follicular fluid. Nor was it affected to any degree by the absence of calcium or by a low (26 degrees C) temperature, both of which are regulators of the physiological AR in other species. By contrast, a clear dose-related enhancement of the AR by the calcium ionophore A23187 was almost completely Ca2(+)-dependent. We conclude that the human cumulus oophorus does not rapidly induce an AR in spermatozoa capacitated in vitro and, unlike the situation in some other mammals, that washed human spermatozoa do not first require a period of capacitation in order to penetrate it. The results also point to the likelihood that ARs monitored in free-swimming human spermatozoa are for the most part spurious or artefactual, and they show that in-vitro AR rates in such populations do not parallel their fertilizing ability.

Acrosome↗
PubMed1990

Vincristine infusion with CHOP-CCNU in diffuse large-cell lymphoma.

Phase I and II trials of vincristine infusion have demonstrated the safety and efficacy of this approach in the treatment of patients with refractory non-Hodgkin's lymphoma. Subsequently, a trial was designed to evaluate this technique in untreated patients. Repeated 5-day infusions of vincristine 0.25 mg/m2 per day were incorporated into a CHOP-CCNU regimen and administered to 24 patients with advanced diffuse large-cell lymphoma. Objective responses occurred rapidly and were observed in 18 (75%) patients in whom 13 (54%) were complete. Toxicity was generally mild to moderate and neurotoxicity appeared to be no worse than typically observed with bolus vincristine. Complete responses have been durable in most patients and 10 (77%) of the complete responders have not relapsed. At this time, 9 (38%) of the total patients remain alive and without evidence of disease from 3.8 to 7.3 years from the start of treatment. One patient died of disseminated gastric cancer at 3.3 years from the start of therapy and there was no evidence of lymphoma at exploratory laparotomy. Infusion of vincristine may be safely incorporated into multiagent chemotherapy programs of the CHOP type for non-Hodgkin's lymphoma. Its potential for protracted nonmyelosuppressive cell kill would appear attractive in designing future trials for this disease.

Adult↗
PubMed1979

Serum alkaline phosphatase determination. Value in the staging of advanced breast cancer.

A retrospective study of 146 patients with metastatic disease was undertaken to verify the clinical impression that radionuclide scanning rarely, if ever, discloses hepatic metastases in breast cancer patients with normal serum alkaline phosphatase (AP) levels. Only two of 39 patients with abnormal liver scans had normal AP levels, and we conclude that liver scans are not necessary as a routine screening method for liver metastases when the AP level is normal. In contrast AP levels were not predictive of bone scan results. All patients with a twofold or greater elevation of the AP level had abnormal bone, liver, or bone and liver scans. Routine AP determinations provide accurate staging information, and their proper use can decrease the cost of initial and follow-up examination of patients with breast cancer.

Alkaline Phosphatase↗
PubMed1979

Chemotherapy versus chemoimmunotherapy in advanced adenocarcinoma of the colon and rectum: a prospective randomized study.

The combination of vincristine, methyl-CCNU, and methotrexate with or without MER-BCG achieved a 2% complete response (CR) and a 11% partial response (PR) with a median duration of 25-29 weeks in 124 evaluable patients with advanced adenocarcinoma of the colon and rectum. Responses were seen in previously untreated patients and in patients refractory to 5-fluorouracil. The median survival of these objective responders (CR + PR) was 57 weeks. The addition of MER-BCG did not appear to influence response rate or duration of survival and was accompanied by significant toxicity. Response was significantly correlated with performance status, sex, and disease free interval and survival with alkaline phosphatase and performance status. Patients with advanced colorectal carcinoma should be stratified according to these variables.

Adenocarcinoma↗
PubMed1979

Written informed consent in patients with breast cancer.

One hundred breast cancer patients, 35 adjuvant and 65 advanced, were interviewed 0-24 months after the start of chemotherapy to assess their knowledge and perceptions of the purposes, risks and benefits of treatment. Prior to therapy, all had been given verbal explanations and had signed informed consent forms explicitly detailing drugs, objectives and possible adverse effects of therapy. Seventeen percent of adjuvant and 29% of advanced patients were unable to name any of their drugs. While most patients recognized distressing side effects such as nausea and hair loss, less than 50% were aware of the potentially lethal complications of infection and bleeding. While the purpose of adjuvant therapy was cure, only 29% of the adjuvant patients were aware of this. In contrast, 35% of the advanced patients incorrectly stated that they were told their therapy was potentially curative. Explanations given by a nurse in addition to a physician were better understood than those given by a physician alone. We conclude that, in spite of intensive efforts at improving informed consent procedures, current results are unsatisfactory.

Adult↗
PubMed1979

Absorbed radiation dose in mammography.

Radiation dose from mammographic techniques was determined as a function of surface exposure, beam quality, and depth. Relative exposure vs. depth was measured in tissue-substitute materials by thermoluminescent dosimetry. The f-factors were calculated from elemental compositions of mastectomy specimens. Dose at depth depends on beam quality as well as exposure and tissue composition. Analysis of data from the ACS/NCI Screening Centers shows current average midbreast doses to be 25 times lower (film/screen) and 3 times lower (Xerox) than the 2 rads previously estimated. Quantitative risk indicators other than midbreast dose are also discussed.

Adipose Tissue↗
PubMed1979

Anthropomorphic test objects for CT scanners.

Numerous types of artifacts can result in clinical misinterpretations in computed tomography. The authors have evaluated phantom materials and techniques of construction which would produce objects similar enough to the human body to test the accuracy of CT in vivo. The object used for this purpose is a thoracic section with five soft-tissue materials, representing adipose tissue, muscle, heart, esophagus, and lung, and three bone materials representing cortical bone, average rib, and "inner" (trabecular) bone. The accuracy of CT numbers for studies of different organs was assessed and sources of error in five commercial scanners were identified.

Adipose Tissue↗
PubMed1978

Adriamycin versus methotrexate in five-drug combination chemotherapy for advanced breast cancer: a randomized trial.

Adriamycin is of noteworthy efficacy in the treatment of metastatic breast cancer. Its role in combination regimens is under investigation. One hundred seventy-five women with advanced breast cancer were entered into a prospectively randomized trial comparing two five-drug regimens. Regimen CMFVP consisted of cyclophosphamide (C), methotrexate (M), 5-fluorouracil (F), vincristine (V), and prednisone (P). Regimen CAFVP was identical but substituted Adriamycin (A) for methotrexate. Twenty-seven patients were disqualified; 148 were evaluable. With CMFVP the complete response rate (CR) was 11%, and the partial response rate (PR) was 46%; with CAFVP, CR was 13% and PR was 45%. Duration of response tended to be slightly longer for patients on the Adriamycin arm. The median survival for CR and PR patients with CMFVP was 20.2 months, which was shorter (p = .07) than the 33 month median survival with CAFVP. Although statistical significance was not reached at the 5% level, the increased survival of responders on the Adriamycin regimen supports the data of other studies which suggest that first line combination chemotherapy in advanced breast cancer should include Adriamycin.

Antineoplastic Agents↗