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Biomedical subjects

J Graczyk

Publications and source records attributed to J Graczyk.

At least 37 records · Page 2Linked to original sources

[Effect of antifolates and folates on the antineoplastic action of fluoropyrimidines].

The influence of folate and antifolate on the cytostatic activity of fluoropyrimidines has been examined extensively. From all of present work, it is apparent that methotrexate can be synergistic or antagonistic in its interaction with 5-fluorouracil, depending on the sequence used and the metabolic machinery present in the target cell. The interaction between commonly administered 5-fluorouracil and leucovorin may enhance carcinostatic efficacy of 5-fluorouracil in patients with colon carcinoma.

Animals↗

The influence of recombinant human tumor necrosis factor-alpha, alone and in combination with cyclophosphamide or methotrexate, on leukemia L1210 and normal hematopoiesis in mice.

We investigated the influence of rh-TNF administered as a single agent or in combination with CY or MTX on the survival time of mice inoculated with lymphoid leukemia L1210 and the effects of similar treatment on normal hematopoiesis in mice. The MST of rh-TNF--treated mice was longer than that of control animals. The longest survivals were observed in mice treated with 250 and 275 micrograms/kg of rh-TNF. Groups of mice receiving a combination of rh-TNF at doses of 225 or 250 micrograms/kg and MTX lived longer than animals treated with these agents separately. We observed the longest survival time of mice treated with combined administration of rh-TNF at a dose of 250 micrograms/kg and CY, but survival time was not significantly prolonged compared with mice receiving only CY. Additional studies were performed to examine the influence of rh-TNF administered as a single agent or in combination with toxic doses of CY or MTX on the number of granulocytes, lymphocytes, erythrocytes with hematocrit values and hemoglobin concentration, and platelets in peripheral blood, and the number of mononuclear cells as well as multipotential stem cells (CFU-GEMM) in bone marrow. Rh-TNF caused dose-dependent suppression of mononuclear cells and multipotential stem cells in bone marrow. The addition of MTX to rh-TNF caused no enhanced suppression of any of the above mentioned hematological parameters. In contrast, the addition of CY to rh-TNF suppressed erythrocytes and hematocrit values, as compared with rh-TNF alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Short-course tuberculosis chemotherapy studies conducted in Poland during the past decade.

During the past decade, six short-course (6-month) chemotherapy regimens were studied in which drugs were given daily and intermittently. Four regimens containing isoniazid, rifampin, and ethambutol caused little toxicity but yielded relapse rates (8-21%) which were unacceptably high. The safety of giving rifampin (450 or 600 mg) twice weekly was confirmed, however, and there was evidence that daily therapy during the 4-month continuation phase was no more effective than twice weekly isoniazid and rifampin. Once weekly therapy during the continuation phase was clearly inadequate. The use of four drugs (isoniazid, rifampin, pyrazinamide, and streptomycin) given daily during the initial 2 months of therapy followed by 4 months of twice weekly isoniazid and rifampin resulted in a nearly 100% cure rate. However, this regimen was not well tolerated by patients. Deleting streptomycin improved the tolerability of the regimen but appears to have slightly increased the frequency of treatment failure and relapse. A suggested model for choosing treatment regimens is presented.

Adolescent↗

Supervised six-months treatment of newly diagnosed pulmonary tuberculosis using isoniazid, rifampin, and pyrazinamide with and without streptomycin.

In a previous study, we have shown that a 6-month regimen consisting of 2 months of isoniazid, rifampin, pyrazinamide, and streptomycin administered daily (2IRSZ) followed by 4 months of isoniazid and rifampin administered twice weekly (4I2R2) yielded no relapses after 30 months of follow-up. In order to assess the contribution of streptomycin to this treatment regimen, 213 patients with newly detected smear-positive pulmonary tuberculosis were randomly assigned to the following two 6-month treatment regimens: 2IRZ/4I2R2 and 2IRSZ/4I2R2. One hundred seventy-two of the 213 patients (81%) completed therapy, i.e., 116 of 135 patients (86%) treated with 2IRZ/4I2R2 and 56 of 78 patients (72%) treated with 2IRSZ/4I2R2. Adverse reactions requiring withdrawal of drugs for 7 days or longer were observed in 4.2% of patients (3.7% receiving the 2IRZ/4I2R2 regimen and 5.1% receiving the 2IRSZ/4I2R2 regimen). At the end of treatment, all patients in the 2IRZ/I2R2 series had negative smears and cultures. Two of the 116 patients (1.7%) in the 2IRZ/I2R2 series developed isoniazid resistance in the fourth month of treatment and remained sputum positive at the end of treatment. In the follow-up period, 4 patients (3.4%) treated with 2IRZ/4I2R2 relapsed and 1 (1.8%) treated with 2IRSZ/4I2R2 relapsed. The only significant difference between the 2 regimens was the higher dropout rate among those assigned to the 2IRSZ/4I2R2 regimen.

Adolescent↗

[Acute toxic effects of trimethyl and triethyl phosphites].

The studies on toxic properties of trimethyl and triethyl phosphities involved: determination of acute general toxic effect on white rats following intragastric and intraperitoneal administration of these compounds, based on DL50 test, determination of damaging effect direction, by histopathological examination of animals' internal organs, determination of intensity of primarily irritating action on the skin, eye and conjunctiva, as well as sensitizing effect on guinea-pigs. DL50 value for trimethyl phosphite following intragastric administration was found to be 2.45 g/kg and following intraperitoneal administration--2.25 g/kg; for triethyl phosphite these values were: 4.00 g/kg after intragastric administration and 1.50 g/kg after intraperitoneal administration, respectively. In local action both phosphites mildly irritate the skin, eye and conjunctiva. A weak sensitizing effect of triethyl phosphite was found. Trimethyl and triethyl phosphites have general toxic effects. A particular direction of their action is demonstrated by acroparalysis. Apart from general action they were found to show systemic action and induce parenchymatous degeneration of the liver and kidneys, whatever route of administration. Administered intragastrically, they result in mucosa necrosis, ulceration and fibrino-purulent exudate, exfoliating the mucosa.

Animals↗