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Biomedical subjects

I Djerassi

Publications and source records attributed to I Djerassi.

At least 19 recordsLinked to original sources
PubMed1988

The safety of administration of massive doses of methotrexate (50 g) with equimolar citrovorum factor rescue in adult patients.

A total of 45 courses of 50 g (24 to 33 g/m2) of high-dose methotrexate (HDMTX) followed by an improved citrovorum rescue (CFR) were administered to 23 patients according to a recently updated procedure. All patients previously had received HDMTX-CFR at lower doses. The HDMTX was administered intravenously (IV) over 6 hours with a priming dose of 8 g followed by 42 g given by continuous infusion. Maintenance of adequate urine output and pH level were achieved with IV fluids, sodium bicarbonate, oral acetazolamite, and a low-acid diet. The CFR was administered by following the equimolar rescue technique and was continued until the serum MTX level was less than 2 X 10(-7) mol/l. The MTX was usually rapidly cleared. The median 48-hour serum MTX level was 7.57 X 10(-6) mol/l (range, 6.8 X 10(-7) mol/l to 7.9 X 10(-5) mol/l). Most patients cleared MTX to below 10(-7) mol/l by the eighth day (range, 5 to 13 days) after MTX infusion. The MTX clearance did not always correlate with the pretreatment creatinine clearance. The toxicity observed included the following: leukocyte count less than or equal to 2000/microliters in 11% of the courses with less than or equal to 1000/microliters in 0%, platelets less than or equal to 10(5)/microliters in 9%, creatinine elevation to greater than or equal to 1.5 mg/dl in 7%, mild mucositis without ulcerations in 33%, nausea with occasional vomiting in 66%, mild skin rash in 18%, and temporary elevation of liver enzymes in 81% of the courses. All side effects were tolerable and transient, and the patients recovered fully. Patients who cleared MTX rapidly (MTX less than or equal to 2 X 10(-6) mol/l at 48 hours) rarely sustained leukopenia, creatinine elevation, or skin rash. Toxicity was not increased by third space fluids or by delaying CFR to 24 hours instead of 12 hours after MTX. The procedure described allows the safe administration of HDMTX-CFR at the 50-g range to adults with advanced malignant solid tumors.

Adult↗
PubMed1986

Rescue from high-dose methotrexate with 5-methyltetrahydrofolate.

5-Formyl-tetrahydrofolate [citrovorum factor (CF)] is commonly used for preventing or reversing toxicity due to treatment with high-dose methotrexate (HDMTX). In vivo, CF is converted to 5-methyltetrahydrofolate (MTHF) and then to the 5,10-methylene tetrahydrofolate, which is the active coenzyme involved in thymidine synthesis. In this study, MTHF was used for protection from toxicity following larger doses of MTX than previously studied, doses which could not be tolerated without effective "rescue." Fifteen patients were given 18 courses of MTX in escalating doses (1-24 g) followed by MTHF. The toxic effects observed included: leukopenia, thrombocytopenia, mucositis, nausea, vomiting, and elevation of serum creatinine and serum transaminase. The side effects were reversible and all patients recovered fully. "Matched pairs" comparison of CF and MTHF rescue in five patients showed no difference in rescue efficacy between the two agents. Since ten of the treatments consisted of 12 and 24 g of MTX, doses potentially fatal without rescue, MTHF is an effective agent for prevention of MTX toxicity.

Adult↗
PubMed1985

Response of astrocytoma to high-dose methotrexate with citrovorum factor rescue.

Eleven patients with astrocytoma were treated with high-dose methotrexate (HDMTX) and citrovorum factor rescue (CFR). Clinical response was observed in eight patients, including four of four with grade 3 disease, one of one with grade 2 to 3, two of four with grade four, and one of one with unspecified low-grade tumor. Two patients with grade 4 and one with grade 1 disease failed to respond. Six of the eight responses were documented radiographically. Three of these patients are alive and well without further treatment for periods of 15+, 4.5+, and 1.5+ years. The fourth living patient is surviving 2+ years and improving under continued treatment. The four surviving patients had recurrent grade 2 to 3 or grade 3 disease. HDMTX-CFR is effective in astrocytoma. Its greatest value may be in recurring grade 3 disease.

Adolescent↗
PubMed1983

A small molecular weight growth inhibitory factor in tissue culture supernatants.

A small molecule in tissue culture supernatants has growth inhibitory effects on the parent and other cells. Supernatants from stationary phase cultures of a human normal lymphoid cell line (No. 802) inhibited the growth of the parent cells even when the latter were in optimal concentrations. The inhibitory activity was associated with small molecular weight fractions prepared by filtration. Fractions with materials smaller than 5000 daltons were the most active. Growth inhibition was observed also with fractions smaller than 2000 and 1000 daltons. Similar growth inhibition of parent cells was observed with the small molecular weight fractions of supernatants from the human acute lymphoblastic leukemia cell line CCRF-SB, the human lung Ca cell line A-549 and from a mouse leukemia L1210 line. The latter were inhibited only in the absence of serum. The fractions from all 3 human cell lines inhibited the cells from all human lines indicating a lack of tissue specificity. The fractions from the human 802 line and the mouse L1210 line did not inhibit the cell growth of each other. Species specificity, however, cannot as yet be considered established.

Animals↗
PubMed1982

The effect of high-dose methotrexate on renal tubules as indicated by urinary lysozyme concentration.

Lysozyme was measured after 186 doses of methotrexate (MTX) to 88 patients. After 7.5% of the doses, lysozyme rose to between 2 and 19 micrograms/cc and in 3.2% it rose to between 20 and 120 micrograms/cc. These increases had no relationship to the age of the patients, their dose of MTX, the total number of times that MTX had been given, nor to rises in serum creatinine. It did correlate with the administration of aminoglycosides (a part of the supportive care of these patients) in two thirds of these cases. In patients who did not receive aminoglycosides, no urinary lysozyme concentration rose above 19 micrograms/cc, not even in the patients who became oliguric or required hemoperfusion. Most of these rises occurred early and were of 24 to 48 hour duration. The rises occurring after five days were persistent and were associated with prolonged MTX serum concentrations, suggesting that tubular damage due to MTX was the result of prolonged exposure to MTX, rather than the primary cause of kidney damage, i.e., the event causing the prolonged serum concentrations.

Adolescent↗
PubMed1982

Breast cancer skin test antigens of increased sensitivity prepared from vesicular stomatitis virus-infected tumor cells.

Crude membrane (CM) extracts were prepared from five cultured breast tumor lines (MDA-MB-157, MDA-MB-231, ZR75-1, HS0578T, and MCF-7) which had been infected with vesicular stomatitis virus (VSV) to augment their antigenicity. In skin test trials, CM extracts of uninfected MCF-7 cells elicited positive response in 0 of 13 (0%) tests in breast cancer patients, while VSV-MCF-7 elicited positive responses in 11 of the same 13 patients (84.6%). CM extracts of VSV-ZR75-1 and VSV-MCF-7 elicited greater delayed hypersensitivity responses (mm induration at 48 hr) in breast cancer patients than in patients with lung carcinoma or melanoma. Although the sensitivity of VSV-ZR75-1 was too low (ten of 28, or 35.7% of tests positive) to be useful as a skin test antigen, VSV-MCF-7 elicited positive responses in 30 of 38 (78.9%) tests in breast cancer patients, as compared to two of 15 (13.3%) and two of 13 (15.4%) of tests in patients with lung carcinoma and melanoma, respectively. The "virus-augmented" CM extract of cultured MCF-7 cells exhibited markedly greater sensitivity as compared to control MCF-7 extracts (P less than .005), with a high degree of specificity for breast cancer patients as compared to patients with the other neoplasms (P less than .00001). The results of skin testing with VSV-MCF-7 CM extracts demonstrated antigenic cross-reactivity with a large number of breast cancer patients, a finding of great importance for any potential immunotherapy and/or immunodiagnosis.

Adult↗
PubMed1980

The Pennsylvania hemophilia program 1973-1978.

In Pennsylvania, the prevalence of hemophilia is one per 10,000 males. Factor VIII deficiency is five times more frequent than Factor IX deficiency, and 34% of the patients have no relatives affected with the disease. The mean age is 23 years old, and 50% of the patients are less than 20 years old. Approximately one-third of the patients with Factor VIII deficiency and one fourth of the patients with Factor IX deficiency have levels of less than 0.01 mu/ml. By clinical criteria, 55% of those with Factor VIII deficiency are severe compared to 45% of those with Factor IX deficiency. Factor VIII-deficient patients are treated an average of 18 times per year compared to ten times per year for patients with Factor IX deficiency. Hemarthroses account for 70% of the hemorrhages treated and for 40% of the concentrate usage. Home therapy patients use an average of 45,950 Factor VIII units per year at a cost of ø170 per patient and their use accounts for 60% of the total Factor VIII usage of 1.7 million units. Less than five days per patient per year are lost from school or work because of bleeding, and patients are hospitalized for bleeding an average of only two to three days per patient year. Adverse immediate reactions to therapy are infrequent. Five percent of patients have persistence of the hepatitis B virus, and 7.5% have inhibitors. The mortality rate is 0.04% per year, with half of the deaths being hemophilia-related.

Adult↗
PubMed1977

A randomized clinical trial of granulocyte transfusions for infection in acute leukemia.

In a prospective, controlled, randomized study to evaluate the efficacy of filtration-leukapheresis granulocytes in granulocytopenic, febrile patients with leukemia, 19 patients received antibiotics alone, and 12 received antibiotics plus daily granulocyte transfusions from ABO-matched donors. In skin-chamber studies the granulocytes appeared at sites of inflammation for at least six hours after transfusion. Infected subjects survived longer if they received granulocytes. Differences between control and transfused patients were greatest in patients with persistent bone-marrow failure, the 21-day survival being 20 per cent in controls, and 75 per cent in transfused patients. Granulocytes appeared to have no effect on the outcome of febrile episodes in which infection was not documented, the 21-day survival being 79 per cent for controls and 88 per cent for transfused patients. The transfusion of granulocytes thus appears to offer a survival advantage to infected, persistently granulocytopenic patients.

Acute Disease↗
PubMed1976

Methotrexate and citrovorum factor rescue in the management of childhood lymphosarcoma and reticulum cell sarcoma (non-Hodgkin's lymphomas): parolonged unmaintained remissions.

High doses of methotrexate (HDMTX), given in pulse infusions of 3 to 30 mg/kg body weight, were studied in 22 children with non-Hodgkin's lymphoma. Sixteen complete and five partial remissions were observed in 21 patients evaluable for remission induction. The dose of MTX was increased stepwise on consecutive treatments until objective tumor response occured. Citrovorum factor rescue (CFR) was used "on demand" when toxicity started to develop, and routinely after 30 mg/kg of MTX. Twelve patients who had no previous chemotherapy were entered in a Phase II study consisting of remission induction with HDMTX and remission maintenance with monthly HDMTX supplemented with one monthly injection of vincristine and Cytoxan and five days of oral 6-mercaptopurine and prednisone. Eleven patients achieved remissions (eight complete and three partial) with HDMTX and one with surgery and radiation followed by HDMTX. The three partial remissions improved to complete remission during remission maintenance. All 12 were given the maintenance cyclic combination chemotherapy. Seven of the 12 patients entered the unmaintained phase of the study. One patient relapsed 6 months after cessation of therapy and died 4 years after diagnosis. Six patients are alive and free of disease 2 1/2 to 5 1/2 years after discountinuing treatment and 4 1/2 to 8 1/3 years after diagnosis. Five of these six patients had advanced (Stage IV) disease.

Child↗
PubMed1976

Immunotherapy for accessible tumors utilizing delayed hypersensitivity reactions and separated components of the immune system.

Courses of repeated delayed hypersensitivity challenge reactions at the sites of tumors have been shown to eradicate malignant and premalignant epidermal neoplasms. Local immunotherapy produces therapeutic responses in malignant and premalignant lesions before they are clinically detectable. This leads to a reduced incidence and prevention of tumors. Immunotherapeutic approaches are effective in controlling the early stages of mycosis fungoides and may aid in the management of the cutaneous manifestations in the late stages of the disease. Immunotherapeutic methods induce regressions of soft tissue lesions of a number of multifocal or metastatic malignant diseases with or without concurrent chemotherapy. Immunotherapeutic effects on tumors are similar with primary and recall antigens. Separated components of the cell-mediated immune system induce regressions of tumors following intralesional or perilesional administration, indicating common factors in host defenses against malignant diseases.

Administration, Topical↗