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Biomedical subjects

E Frei

Publications and source records attributed to E Frei.

At least 253 records · Page 14Linked to original sources
PubMed1983

Nitrosamine metabolism in kwashiorkor rats.

The in vitro metabolism of nitrosodimethylamine (NDMA) was studied in liver tissue obtained from male weanling kwashiorkor wistar rats. The elimination of this compound and that of nitrosomorpholine (NMOR) from the blood, after a single intravenous dose, was also investigated. N-demethylase activity in liver microsomes of the test animals was not significantly different from that of the controls although the activity of this enzyme per gram wet liver tissue was considerably reduced in the model animals. On the other hand, the glutathione (GSH) content in liver cytosol of the kwashiorkor animals was much higher than that of the controls. The elimination of NDMA and NMOR from the blood of the experimental animals over 8 hr following i.v. administration of the carcinogens, showed that the clearance rate of each nitrosamine was significantly lower in the kwashiorkor rats.

Animals↗
PubMed1983

Survival of patients with localized high-grade soft tissue sarcoma with multimodality therapy. A matched control study.

Ten of 16 consecutive patients (63%) with Stages III-IVA soft tissue sarcoma presenting between 1975 and 1978 and treated with surgery, radiotherapy and adjuvant chemotherapy have remained disease-free with a median follow-up of three years (range, 28-68 months). Survival at three years was 86%. However, in the American Joint Committee (AJC) soft tissue sarcoma staging system published in 1977, Grade 3 soft tissue sarcomas were associated with a three-year survival of 35% and almost 90% of the patients destined to fail did so within three years of diagnosis (8). To determine if the observed improvement in survival resulted merely from lesions with favorable prognostic determinants at diagnosis, study patients were matched for stage, histologic type and location of the primary lesion with controls generated from these 1215 carefully reviewed sarcoma patients collected from the data base of the Task Force on Soft Tissue Sarcomas of the AJC. Only control cases whose histology had been reviewed and who had been treated with surgery (with or without radiotherapy) were included in the analysis. Cases survived significantly longer than controls at three years (p less than 0.001) and, in fact, disease-free survival of cases (63%) was superior to overall survival of controls (27%) (p less than 0.01). Our data support the conclusion that patients with high-grade soft tissue sarcoma treated by an experienced multimodality team have a three-year disease-free survival of approximately 63%. The impact of each component of multimodality therapy cannot be determined, and improved survival may result, in addition, from improved diagnostic and staging techniques currently available.

Adult↗
PubMed1983

Immunological and cytogenetic studies in two cases of B-cell acute lymphoblastic leukemia (Burkitt's type).

Immunological and cytogenetic studies were performed on two patients who presented with L-3 acute lymphocytic leukemia (Burkitt-type). Surface marker studies showed that both had B-cell leukemias. The blast cells in Case 1 expressed monoclonal IgM kappa surface immunoglobulin and in Case 2, IgG kappa. In the first case, cytogenetic analysis of bone marrow revealed the presence of a rare variant translocation involving the short arm of chromosome 2 and the long arm of chromosome 8 in all the metaphases examined. This is the second report of such a translocation in Burkitt's leukemia. The 8;14 translocation reported in classical Burkitt's lymphoma and other B-cell lymphomas was present in all the bone marrow metaphases in the second case.

Adult↗
PubMed1983

Plasma fibronectin and associated variables in surgical intensive care patients.

An acute depletion of plasma fibronectin or FN has been observed in critically ill, surgical, or trauma patients, but there is little information on the relationships between FN levels and the final outcome in such cases, and on the simultaneous behaviour of other serum proteins. The daily values of FN, antithrombin III, IgG, C3, prealbumin, and transferrin were monitored in 98 intensive care patients after major elective surgery or trauma. According to their clinical course, they were divided retrospectively into three groups. Group A (33 patients) had sepsis. Group B (31 patients) had nonseptic complications, and group C (34 patients) had no complications in the ICU. The individual, nadir levels of FN, AT III, prealbumin, and transferrin were lower (p less than 0.01) in the septic group A than in B and C. Within the septic group, the nadir levels of AT III, but not those of FN, were lower (p less than 0.01) in the 14 nonsurvivors than in the 19 survivors. The FN and AT III levels had returned at least temporarily to the normal range in the six ultimate fatalities from sepsis who survived for more than two weeks. In the septic group, transferrin showed the highest percentages of actually subnormal levels and differed from FN in this respect with p less than 0.05. Furthermore, all six proteins showed a significant overall pattern (p less than 0.01) of parallel variations. The results confirm other reports on the behavior of fibronectin in septic patients as a group, but it was not informative as to the individual outcome, and its reduction might be viewed as part of a general plasma protein depletion associated with acute septic disease. This pattern is probably attributable to a combination of intravascular consumption and an overall excess of protein catabolism over synthesis.

Adolescent↗
PubMed1983

Improved prognosis of diffuse histiocytic and undifferentiated lymphoma by use of high dose methotrexate alternating with standard agents (M-BACOD).

A new combination chemotherapy program (M-BACOD) was administered to 101 patients with advanced diffuse histiocytic and diffuse undifferentiated lymphoma (DHL and DUL). High dose methotrexate (M) 3 g/m2 with leucovorin factor rescue was given on day 14 between cycles of bleomycin (B), adriamycin (A), cyclophosphamide (C), oncovin (O), and dexamethasone (D) administered every 3 weeks for 10 cycles. The complete remission rate (CR) was 72% in all 101 patients or 77% in 95 evaluable patients. The median follow-up is 3 yr 2 mo with one-third of CR patients followed beyond 4 yr. Twenty-six percent of CR patients have relapsed with a projected 5-yr survival rate of 80% (5-yr disease-free rate 65%). The overall survival of all 101 study patients reaches a plateau at 59% projected out to 5 yr. Patients with prior therapy had a significantly lower CR rate than those without prior treatment (p = 0.001); however, no other unfavorable prognostic characteristics could be identified. Relapse in the central nervous system CNS occurred in only 5.4% of CR patients. M-BACOD results in prolonged survival and possible cure in a high proportion of all patients with DHL and DUL.

Actuarial Analysis↗
PubMed1983

Osteogenic sarcoma: alterations in the pattern of pulmonary metastases with adjuvant chemotherapy.

The number and time to appearance of pulmonary metastases were evaluated in 15 patients with osteogenic sarcoma receiving adjuvant chemotherapy with high-dose methotrexate and doxorubicin (adjuvant group). The results were compared to 33 age- and sex-matched controls (control group). The adjuvant group demonstrated a reduction in the number and a delay in the appearance of the metastases. The median time to development of metastases was 17 mo in the adjuvant group and 7 mo in the control group, and the median number of metastases was 2 and 12, respectively.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Influence of intensive asparaginase in the treatment of childhood non-T-cell acute lymphoblastic leukemia.

Between June 1977 and December 1979, 72 evaluable patients with childhood non-T-cell acute lymphoblastic leukemia were induced into complete remission using vincristine, prednisone, and doxorubicin. All received asparaginase consolidation and central nervous system prophylaxis with cranial irradiation and intrathecal methotrexate. All patients then received prolonged intensification with vincristine, prednisone, and doxorubicin, and half of them were randomized to receive weekly high-dose asparaginase. Continuation therapy was with vincristine, prednisone, methotrexate, and 6-mercaptopurine. After a median follow-up of 57 months, there were four remission deaths and 25 relapses. Central nervous system relapse was the first event in 4% of patients. There were fewer treatment failures in the asparaginase-treated group [2-sided, p = 0.04 (0.07 controlling for standard and high-risk groups)]. Asparaginase toxicity occurred in six patients (8%) and was self-limited, but it precluded further use of the drug in those patients. The major toxicity of this treatment program was drug-induced cardiomyopathy which occurred in 10 patients (14%) and was fatal in three of them. In summary, we conclude that the intensive use of high-dose asparaginase has an important role in the treatment of children with acute lymphoblastic leukemia. The morbidity of multiple doses of doxorubicin outweighed its antileukemic advantage in standard-risk patients.

Adolescent↗
PubMed1983

Phase I trial of mitoxantrone by 24-hour continuous infusion.

Mitoxantrone (DAD) is a new agent which intercalates into DNA. Preclinical studies have demonstrated activity equal to or greater than that of doxorubicin in all tumor systems tested. In this phase I clinical trial, the schedule of drug administration consisted of a 24-hour continuous iv infusion repeated at 21-day intervals. Twenty-nine patients received a total of 66 courses over a dose range of 4-15 mg/m2. The dose-limiting toxic effect was leukopenia, with a wbc count nadir on Day 12 and resolution prior to Day 21. Other toxic effects were thrombocytopenia, mild phlebitis, and blue discoloration of veins. Objective tumor responses were seen in a patient with adenocarcinoma of the breast and in another patient with clear cell carcinoma of the vagina. An additional six patients with acute leukemia were treated at a dose of 12 mg/m2; a decrease in peripheral blast count was observed in four of these six patients. The toxicity of DAD by 24-hour iv infusion was similar to that previously reported for iv bolus administration. We recommend phase II evaluation of DAD at a dose of 12 mg/m2 by single iv injection at 21-day intervals. Patients with acute leukemia should be evaluated at higher dose levels.

Adolescent↗
PubMed1982

Clinical cancer research: an embattled species.

Clinical cancer research is at a crossroads. The major progress which has been achieved will continue, provided that factors which threaten the clinical cancer researcher are identified and corrected. These problems (with proposed solutions) include: the increasing number of clinical oncologists, particularly medical oncologists; the relationship of the practicing clinical oncologist to cancer centers; the relative attractions of clinical practice, on the one side, and basic science on the other, as compared to clinical cancer research; the lack of recognition that clinical cancer research provides an opportunity for high achievement and challenge, and originality; the threat of curtailment of research funding; jurisdictional and other conflicts between scientific and clinical disciplines; the emerging "establishment generation" of clinical oncology; and the bureaucratic and regulatory ambience that has increasingly enveloped the clinical cancer researcher. That opportunities for originality continue was illustrated by a new therapeutic surgery known as neoadjuvant or anterior chemotherapy. In this strategy, systemic treatment is employed prior to surgery and/or radiotherapy for patients with head and neck cancer has increased operability ("upstaged" the patient) and on preliminary analysis would appear to be increasing disease-free survival. A clinical trial in osteogenic sarcoma involving initial chemotherapy has indicated that such treatment not only provides substantial regression of the primary in the majority of patients but also results in a substantially improved disease-free and overall survival, particularly in patients with locally responsive disease.

Antineoplastic Agents↗
PubMed1982

Effects of disulfiram on mixed function oxidase system and trace element concentration in the liver of rats.

Disulfiram (DSF), an inhibitor of chemically induced carcinogenesis, and its metabolite diethyldithiocarbamate (DDTC) have been investigated for their influence on trace element distribution and on certain enzymes of the drug metabolizing system in the livers of phenobarbital (PB) treated rats. Both substances diminished the PB induced enzyme response in liver microsomes, DDTC being more effective (-85%) than DSF (-60%). The copper, cobalt and zinc content of the livers of DSF treated animals were increased by factors of 6, 3 and 1.5 respectively as compared to controls, while DDTC treatment had no influence on liver trace element content. A correlation between enzyme inhibition and enhanced trace element uptake of the liver after DSF administration could not be observed. The change of trace element transport into the liver during DSF treatment is discussed.

Animals↗
PubMed1982

The National Cancer Chemotherapy Program.

The National Cancer Chemotherapy Program was initiated in 1955. It is administered and integrated by the Division of Cancer Treatment at the National Cancer Institute. The program involves the discovery and development of potential new antitumor agents; their screening in preclinical experimental systems for antitumor effect, and, if active, for toxicology; and, for selected agents, preliminary, and more definitive clinical trials. While serendipity and empiricism played a substantial role in the early years of the program, the program has increasingly emphasized and been influenced by advances in tumor biology, drug development, clinical pharmacology, and the science of clinical trials. There has been effective interaction between investigator-initiated research on the one hand and developmental research at preclinical and clinical levels on the other. Over 30 chemotherapeutic agents with substantial clinical antitumor activity have been discovered, and their proper use, often in combination and often integrated with surgery or radiotherapy, has resulted in significant progress in the effective treatment of many forms of cancer.

Antineoplastic Agents↗