[Drug therapy of bacterial infections in patients with kidney failure and hemodialysis].
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Biomedical subjects
Publications and source records attributed to F Yamasaku.
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In 90 suspected cases of beta-lactam hypersensitivity manifesting exanthema, pyrexia and hepatopathic symptoms, the identities of the allergenic drugs were investigated by immediate type skin reactions, sensitized erythrocyte agglutination tests and leucocyte migration inhibition tests (LMIT). In addition 30 control patients were tested for hypersensitivity to ampicillin, cephalexin and latamoxef. The control patients manifested the same symptoms as the patients with suspected hypersensitivity to beta-lactam but had not been treated with beta-lactam antibiotics. In the immediate type skin reaction, all the control cases as well as all the suspected beta-lactam hypersensitive patients displayed negative reactions to each of the antibiotics tested. In the sensitized erythrocyte agglutination tests, no antibodies to any of the three drugs were detected in the control group, while antibodies with a titre of 1:2 or more were detected in only 7% (6/90) of the suspected beta-lactam hypersensitive patients. On the other hand, in the LMIT, only 4% (4/90) of the control patients displayed positive reactions to the three test antibiotics, whereas the suspected sensitizing drugs elicited a high rate of positive responses (68/90; 76%) in the group of suspected beta-lactam hypersensitive patients. Broken down into symptomatic categories, response to the LMIT was positive in 41 of 58 cases of suspected drug rash (71%), 26 of 26 cases of suspected drug fever (96%), and 20 of 24 cases of suspected drug-induced hepatopathy (83%). Thus, the pyrexial group exhibited a particularly high ratio of positive reactions, and in fact exanthemic cases with concomitant symptoms (eosinophilia, pyrexia, hepatopathy, etc.) also displayed a notably high ratio of positives (19/20; 95%). The overall results indicated that delayed type hypersensitivity (DTH) is largely involved in exanthema, pyrexia and hepatopathy induced by beta-lactam antibiotics, and that the LMIT constitutes an effective means of detecting allergenic drugs in patients with beta-lactam hypersensitivity.
Cross-reactivity associated with delayed type hypersensitivity (DTH) arising from cephem antibiotics with a tetrazolyl group in the C-3 side chain was investigated by clinical testing and animal experiments. Clinical cross-reaction testing was performed with the leucocyte migration inhibition test (LMIT) with respect to sixteen patients with hypersensitivity induced by cephems with a tetrazolyl group in the C-3 side chain. The proportion of positive LMIT cross-reactions to cephems with a tetrazolyl group in the C-3 side chain was 78% (25/32), to cephems without a tetrazolyl group, 5% (1/22), and to penams, 0% (0/12). The proportion of positives in tests performed with methyl-tetrazolethiol (MTT) and hydroxyethyl-tetrazolethiol (HTT), which essentially represent the structures of the C-3 side-chains in the allergenic drugs, was 29% (4/14), while the corresponding proportion for 7-aminocephalosporanic acid (7ACA), which represents the skeleton structure of the cephem antibiotics, was 33% (1/3). The animal experiments were performed with guinea pigs, with latamoxef, cefoperazone and MTT as the sensitizing agents and testing for cross-reactivity by means of delayed type intradermal reactions as well as the LMIT. The results of intradermal testing and the LMIT agreed almost completely, thus providing strong support for the clinical results. Latamoxef and cefoperazone displayed the same cross-reactivity, manifesting cross-reactions with MTT, HTT and 7ACA as well as with cephems having a tetrazolyl group in the C-3 side chain. Moreover, DTH induced by MTT displayed cross-reactivity with cephems possessing tetrazolyl groups in the C-3 side chain. The above results indicate that free MTT radicals, as well as the skeleton ring structure represented by 7ACA, are strongly involved in DTH arising from cephem antibiotics with a tetrazolyl group in the C-3 side chain.
Astromicin (ASTM) was administered intravenously to 4 healthy adult volunteers with an average body weight of 62 kg using a continuous infusion apparatus at a constant rate of 200 mg in 1 hour (Group I), 400 mg in 1 hour (Group II) and 200 mg in 2 hours (Group III). Concentrations of the drug in serum and urine were determined by high power liquid chromatography (HPLC). The mean serum concentration of the 4 subjects reached the peak of 13.32 micrograms/ml in Group I, 22.12 micrograms/ml in Group II and 9.89 micrograms/ml in Group III. The peak concentration was achieved at the end of infusion and was dose-related. After 8 hours, the concentration dropped to less than 1 micrograms/ml in all groups. The urinary recovery rate was 90% in 8 hours and 95% in 24 hours. T1/2 (beta) analyzed by the two-compartment open model was 1.64-1.72 hours. AUC infinity was also dose-related, such as 33.1 micrograms X hr/ml and 31.6 micrograms X hr/ml in Group I and Group III, and 57.6 micrograms X hr/ml in Group II. It is recommended for amikacin (AMK) that the peak serum concentration should not exceed 35 micrograms/ml and the maximum concentration before the next infusion should be less than 5 micrograms/ml. In these experiment, ASTM which is lower in toxicity than AMK did not approach 35 micrograms/ml even at the peak level with the dosage of 400 mg in 1 hour. Furthermore, the excretion of the drug was fast and the serum level of the drug became much lower than 5 micrograms/ml very quickly.(ABSTRACT TRUNCATED AT 250 WORDS)
A 79-year-old woman with primary liposarcoma of the heart, an extremely rare malignancy, coexistent with Brenner tumor was reported. The histological features of the sarcoma on the routine histological slides were so varied that it was necessary to differentiate the histology from that of malignant fibrous histiocytoma or pleomorphic rhabdomyosarcoma. Most of the tumor cells including fibroblastic and bizarre giant cells, however, were stained intensely with histochemical methods for lipids and consequently diagnosed as pleomorphic liposarcoma originated from the epicardium. Electron microscopically, lipid droplets were demonstrated in the cytoplasm of the tumor cells, supporting the histological diagnosis. No distant or nodal metastases were noted.
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The basic pharmacokinetics of micronomicin (MCR) were studied in 4 healthy adult volunteers. MCR 60 and 120 mg were intravenously administered in 30 and 60 minutes at constant rates by means of continuous infusion apparatus. The same dosages were also tested by intramuscular route. The concentrations of MCR in serum and urine were determined by HPLC and analyzed following the two-compartment open model after intravenous treatment and following the one-compartment open model after intramuscular treatment. When MCR was given by intramuscular route, the mean serum concentration of 4 subjects reached a peak of 3.98 micrograms/ml at 30 minutes after a dose of 60 mg and 6.7 micrograms/ml at 30 minutes after that of 120 mg. The peak concentration was achieved at the end of intravenous infusion and was dose-related, since it was 6.1 and 10.5 micrograms/ml after a 30-minute infusion of 60 and 120 mg, respectively, and 4.85 and 9.43 micrograms/ml after a 60-minute infusion of 60 and 120 mg, respectively. At 8 hours, concentrations dropped to less than 0.1 microgram/ml and to 0.2 microgram/ml or less after 60 and 120 mg, respectively, regardless of the route and rate of administration. The mean urinary recovery up to 8 hours ranged 84 to 92% of the dose. There were no appreciable differences in pharmacokinetic parameters among 4 modes of intravenous infusion, with a T1/2(beta) of 1.43 approximately 2.02 hours. In the case of intramuscular treatment, parameters analyzed following the one-compartment open model were on similar levels to corresponding values found after intravenous treatment and the T1/2 was 1.39 hours after 60 mg and 1.43 hours after 120 mg.(ABSTRACT TRUNCATED AT 250 WORDS)
Tobramycin (TOB) was administered to 4 healthy adult volunteers (mean body weight 63.5 kg, surface area 1.71 m2) as one time 90 mg dose by intramuscular injection or by intravenous infusion (30 or 60 minutes) in a crossover study. Serum and urinary concentrations were assayed by bioassay and radioimmunoassay (RIA). Pharmacokinetic analysis was done with a one-compartment open model in the case of intramuscular injection and a two-compartment open model in the case of intravenous infusion. The correlation constant was 0.92, and the relation formula was y = 0.81x+0.13 between bioassay and RIA. In the case of intramuscular injection, the peak serum concentration was 5.1 approximately 6.3 mcg/ml (mean 5.3 mcg/ml), and values calculated with pharmacokinetic parameters from the mean serum concentration were Tmax = 0.745 hour, Cmax = 5.34 mcg/ml and half life (T1/2) = 89.6 minutes. With 60 minutes intravenous infusion, the peak serum concentration was 6.7 approximately 9.1 mcg/ml (mean 7.5 mcg/ml), and the calculated value was 7.63 mcg/ml. The value after 2 hours was nearly equal to those for intramuscular injection. T 1/2 of beta-phase was 95.8 minutes. With 30 minutes intravenous infusion, the peak serum concentration was 8.4 approximately 11.8 mcg/ml (mean 10.2 mcg/ml), and the calculated value was 9.81 mcg/ml. T 1/2 of beta-phase was 105.3 minutes and the serum concentration of the beta-phase was same as that for intramuscular injection administration after 6 hours. We concluded that 60 minutes intravenous infusion of TOB 90 mg is more effective and safe than the 30 minutes method from the standpoint of toxicity, and the serum concentration of the beta-phase is similar to that with intramuscular injection. With each administration method, urinary recovery was 70 approximately 80% for 8 hours.
Ribostamycin is an aminoglycoside antibiotic produced by Streptomyces ribosidificus, and extracted and isolated by NIIDA et. al. It has been used widely clinically with its characteristic of low ototoxicity. UMEMURA et al. studied the pharmacokinetics of this antibiotic in animals and reported that it has a similar pharmacokinetic behavior in vivo to kanamycin. In the present studies, the pharmacokinetic behavior of ribostamycin was studied in 5 healthy adult volunteers receiving different doses (0.5 g, 1.0 g and 1.5 g) by intramuscular injection, and 0.5 g by intravenous drip infusion. In addition, a similar study was conducted with 11 patients with varying degrees of renal dysfunction in order to study the application of ribostamycin in such patients.
Using 6 healthy adult male volunteers, who were divided in halves, the serum and urinary levels of cephaloridine were determined during and after 2-hour constant drip infusion of 2 g cephaloridine dissolved in 500 ml physiological saline solution (= Group I) and 1-hour constant drip infusion of 1.5 g solution (= Group II); besides, pharmacokinetic analysis was made for one-compartment and two-compartment models. On the basis of the values of serum levels obtained from this trial, pharmacokinetic parameters were calculated and simulation curves of serum levels for various doses (0.5 approximately 2 g) and duration (1 approximately 4 hours) of cephaloridine drip infusion were drawn.
1) The half-life of serum concentration of cephradine (CED) in patients with normal renal function, was 30 minutes and it prolonged to 83 minutes when combined with probenecid. 2) In the patients with severely impaired renal function, mean serum concentration of CED was 33 mcg/ml 24 hours after 1 g intravenous injection. 3) In clinical observations of 17 cases with infections of lung, urinary tract, and bile duct, the treatment with CED showed excellent results in 5 cases, good in 6, undetermined in 1. No remarkable side effect was observed.
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