Small intestinal transplantation and cyclosporine predose calculation.
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Biomedical subjects
Publications and source records attributed to F Lokiec.
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Diethyl-1-[3-(2-chloroethyl)-3-nitrosoureido]ethylphosphonate (S 10036) is a new nitrosourea that has been evaluated in a clinical trial because of its activity in the National Cancer Institute panel screen and its rational chemical approach. A Phase I study was conducted in 22 evaluable patients with advanced cancers. The drug was given as a slow i.v. infusion over a period of 60 min on days 1, 8, 15, and 22 followed by a 4-week rest period. The dose levels ranged from 25 to 200 mg/m2/week for 4 consecutive weeks using a modified Fibonacci scheme. Thrombocytopenia was the only acute dose-limiting toxicity and started at a dose of 100 mg/m2/week and above. Hematological toxicity was delayed, cumulative, and dose related. Nausea and vomiting were moderate to severe and dose related. Three responses (one complete and two partials) have been noted. Phase II studies of S 10036 are planned at a dose of 100 mg/m2/week for 4 consecutive weeks ("induction therapy") for patients without prior therapy and 100 mg/m2/week for 3 consecutive weeks for those with prior chemotherapy or radiotherapy. Because of the cumulative toxicity, the recommended dose for the second cycle of S 10036 chemotherapy ("maintenance therapy") is 100 mg/m2/week every 3 weeks.
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A simple reliable liquid chromatographic method for assay of cyclosporin A in serum or urine is described. Samples were cleaned up on a solid-phase extraction system (cyanopropyl column). The system involved a reversed-phase C18 Ultrasphere column maintained at 72 degrees C and an acetonitrile linear gradient (65 to 95%) in 0.14% triethylammonium phosphate. Liquid chromatographic analysis of radioimmunoassay standards shows that some samples contain a contaminant peak. Comparison of cyclosporin A levels obtained by radioimmunoassay and high-performance liquid chromatography in clinical investigations show that the former values are generally, but not always, higher than the latter, and that cyclosporin A is very differently metabolized depending on the patient, disease and treatment.
Twenty patients undergoing gastrointestinal surgery were randomly allocated to receive either 1 or 2 g of ceftriaxone, a long half-life third generation cephalosporin, as a single dose intravenous prophylaxis on induction of anaesthesia. Plasma and tissue samples were taken 2 hours and analysed with an HPLC procedure. The results of plasma and tissue concentrations of ceftriaxone showed that 1 g dosage was enough for preventing the occurrence of postoperative sepsis. No adverse reaction or side-effects were recorded.
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Percutaneous lateral discectomy (PLD) in a 32-year-old man was followed by postoperative disc space infection and adjacent vertebral osteomyelitis caused by Staphylococcus aureus. The simplicity and decreased morbidity associated with PLD may be offset by severe infections. The small incision made in the annulus during PLD may not allow adequate drainage in the case of infection and may subsequently direct the infective process to the adjacent vertebral endplates. Meticulous aseptic technique, and possibly the use of prophylactic antibiotic therapy, is important in PLD.
Following intravenous administration of 2 g ceftriaxone, concentrations of the drug were assayed in serum, in thoracic duct lymph from dogs, and in mesenteric lymph nodes in patients. Antibacterial activity of lymph against S. typhi was also studied. Results show that ceftriaxone concentrations in serum and lymph are comparable; with a satisfactory antibacterial activity of both fluids against S. typhi. In mesenteric lymph nodes, mean ceftriaxone concentration was approximately 1000 times the MIC for S. typhi. Our data contribute to explain the successful clinical results achieved with ceftriaxone in patients with typhoid fever.
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We used the test-dose method to calculate the dose of methotrexate to administer to the patients to reach the therapeutic but non-toxic blood concentration of 10(-5) mol/L. Methotrexate was tested with a radioimmunoassay technique and in 19 out of 20 patients we obtained the desired plateau during 24-h infusion.
Simultaneous assays of platelet factor 4 (PF-4) and beta-thromboglobulin (beta TG) were performed in 192 cases of myeloproliferative syndromes (polycythaemia vera and primary thrombocytosis, as defined by the Polycythaemia Vera Study Group). The results led to the following conclusions: (I) both assays must be combined in order to avoid a poor interpretation due to marker release in vitro; (II) the 'normality' of the values must take the platelet number into account, even in the 'normal' range of this parameter; (III) the sensitivity of the beta TG assay is greater than that of PF-4 when considering the correlation of the marker values with arterial accidents; (IV) the predictive value of an excessive level of beta TG and/or PF-4 is difficult to define, since only 13 of the cases studied had a vascular accident during the 12-month follow-up period, and the levels of the markers in these patients were not statistically different from the levels in those patients not experiencing such accidents.
Sodium butyrate at a concentration of 1 x 10(-3) M or lower seems to decrease the rate of cellular proliferation through the cell cycle in G 1 phase. This effect makes them more sensitive to the cytotoxic action of moderate doses of methotrexate.
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The kinetics of methotrexate were studied in a group of 59 patients after infusion of high doses. From the triexponential analysis of the serum concentration curve, rate constants and relative concentrations in non-circulating pools were calculated, using a linear 'mammillary' three-compartment model. No significant variation as a function of dose (300-6,000 mg/m2) was observed. In circumstances the rapidly exchanging pool was a reflection of the circulating pool, suggesting that it is an extravascular, protein-bound pool of methotrexate. Considerable variations of the relative concentration and rate constants of the slowly exchanging pool were observed to be a function of the duration of methotrexate infusion, the presence of other drugs, and the patient's age. If this compartment is assumed to include the target cells for methotrexate, then the large variations observed could be responsible for individual differences in toxicity and/or effectiveness.