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Biomedical subjects
Publications and source records attributed to G A Ratkin.
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In order to determine the minimal toxic dose of a 5-day infusion of 5-fluorouracil (5--FU) in combination with an infusion of thymidine (TdR), 12 patients, received TdR at a dose of 8 g/m2/day for 5 1/2 days, beginning at the same time as a 5-day infusion of 5-FU at doses of 5--20 mg/kg/day. Myelosuppression was the dose-limiting toxicity, and the minimal toxic dose of 5--FU was found to be 7.5 mg/kg/day. Gastrointestinal toxicity was minimal to absent. In eight patients with carcinoma of the colon who had received no prior chemotherapy, there were two patients with partial responses (at doses of 5.0 and 7.5 mg/kg/day of 5--FU), two patients with stable disease, one patient with progressive disease, and three patients with early death (two drug-related deaths and one disease-related death). In four patients who had received prior 5--FU, one had stable disease, one had progressive disease, and two had early death (one drug-related death). We conclude that the addition of TdR to 5--FU infusions changes the dose-limiting toxicity from gastrointestinal toxicity to myelosuppression. The minimal toxic dose is decreased to approximately one third of that when 5--FU is administered alone.
A 19-year-old man with documented infectious mononucleosis presented with pancytopenia and a megaloblastic bone marrow. He developed a "capillary leak syndrome" with an expanded plasma volume of 9,290 ml and normal right heart and pulmonary artery pressures. The patient had a dramatic recovery after corticosteroid therapy.
A staging laparotomy and splenectomy were performed in 41 patients with Hodgkin's disease and 11 with other malignant lymphomas. There was a significant correlation (P = 0.025) between the presence of unexplained anemia and involvement of the spleen or abdominal lymph nodes by tumour. The anemias were of mild degree; hemolysis was documented in three and iron deficiency in four, while 21 cases were unexplained. Bone marrow was not involved by lymphoma in this series. The complication rate in exploratory laparotomy was higher than previously reported. Severe complications were observed in 17% of these patients while another 15% had minor complications. The association we have discovered may be helpful in the staging of patients who cannot tolerate an operative procedure. The absence of infradiaphragmatic involvement is suggested in the presence of normal hemoglobin concentrations.
The Jamshidi-Swaim biopsy needle was utilized to perform 205 bone marrow biopsies, accompanied by simultaneous bone marrow aspirates, on patients with lymphoma, leukaemia, and a variety of solid tumours. There was no significant morbidity. There were 67 positive findings with biopsy and 42 with aspiration. The two techniques were complementary in Hodgkin's disease, non-Hodgkin's lymphoma, breast carcinoma, bronchogenic carcinoma, malignant melanoma, and in leukaemia. We have examined the bone marrow biopsies and aspirates with respect to the adequacy of the bone marrow biopsy specimen, the number of positive biopsies in the various categories of neoplasia, and the disparity of biopsy and aspirate, finding that 28 of the 67 positive biopsies (41.8%) had negative aspirates. These data and specimens obtained compared quite favourably with other series in which a modification of the Vim-Silverman needle was used.
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A total of 232 leukaphereses were performed with a continuous flow (CFC) of 89 donors related to recipients to obtain granulocytes for infected granulocytopenic recipients. One hundred fifteen runs were done without pretreatment of the donors and were used as controls. Pharmacological pretreatment of the remaining one hundred seventeen donors included Prednisone, given in an oral dose (50 mg) the evening prior to the run, and/or 250ml of 6 per cent hydroxyethyl starch added to the input line of the CFC throughout the run. A median of 9.2 liters of donor blood was processed with each run. The pretreatment of the donors with Prednisone plus the addition of HES to the input line significantly increased the number of granulocytes collected. Donors tolerated the leukapheresis procedure well, and no significant side effects were associated with Prednisone or HES administration. Early and frequent use of such granulocytes was effective in the short-term control of fever in the granulocytopenic recipients who failed to respond to 48 hours of broad spectrum antibiotic coverage.