Flomoxef (FMOX, 6315-S), a new intravenous cephem antibiotics, was administered to a total of 11 cases with their ages ranging from 7 years and 4 months to 10 years and 10 months. Among them, two were administered with (FMOX at) a dose level of 10 mg/kg, three each with 20 mg/kg and 40 mg/kg using one shot intravenous injection, and the remaining 3 with 40 mg/kg by intravenous drip infusion over 30 minutes. Plasma concentrations, urine concentrations and urinary recovery rates were determined. The clinical efficacy of FMOX was evaluated in 2 cases with tonsillitis, 45 with acute pneumonia, 10 with urinary tract infections, 2 with purulent lymphadenitis, and 2 with abscess, a total of 61 cases. Of these cases, one case of pneumonia in which a side effect occurred was excluded from the evaluation because the treatment was interrupted short of the required period. In the remaining 60 cases, the mean daily dose was 79.3 mg/kg in 3 or 4 divided doses and, except one case treated by 30-minute intravenous drip infusion, all cases were treated by one shot intravenous injection for a mean period of 6 days. Bacteriological effects of FMOX, its side effects and influences on laboratory test values were also investigated. 1. Maximum plasma concentrations after one shot intravenous injections of FMOX occurred at 5 minutes after administration regardless of dose levels (10 mg/kg in 2 cases, 20 mg/kg in 3 and 40 mg/kg in 3). Mean peak values obtained upon the 3 different dose levels were 62.5, 103.1 and 244.7 micrograms/ml, respectively. Mean plasma half-lives were 0.670, 0.915 and 0.595 hour, and mean AUCs were 33.0, 65.2 and 133.1 micrograms.hr/ml, respectively. Thus, a positive dose-response relationship was found among the 3 doses. 2. Plasma concentrations after 30-minute intravenous drip infusions of FMOX at 40 mg/kg always reached a peak at 30 minutes after the initiation of infusion, i.e. at the completion of infusion, and the mean value for 3 administrations was 151.0 micrograms/ml. The mean half-life was 0.973 hour and the mean AUC was 149.1 micrograms.hr/ml. 3. Maximum concentrations in urine after one shot intravenous injections of FMOX were always obtained in 0 approximately 2 hours after administration regardless of dose levels (10 mg/kg, 2 cases, 20 mg/kg, 3 cases and at 40 mg/kg, 3 cases) and mean values for the 3 dose levels were 2,570, 4,410 and 6,290 micrograms/ml, respectively. Thus, urine concentrations were also dose-dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

PubMed1987

[Fecal and urinary excretion of norfloxacin in adults].

Norfloxacin (NFLX) a synthetic oral antibacterial agent of quinolone carboxylic acid, was given to 6 healthy men aged 23 to 29 years and weighing 57 to 88 kg (average 64.7 kg) at a dose of 200 mg (two 100 mg tablets) once after breakfast and its fecal and urinary recoveries were determined for 5 days after the administration. Fecal and urinary recoveries of NFLX or ciprofloxacin (CPFX) were examined under various experimental conditions where the drugs were added to the urine or feces. Effects of the drug on the clinical laboratory test parameters and side effects were also examined. The following results were obtained. 1. NFLX reached the highest level in the feces in 5 cases in 24 hours and in 1 case in 48 hours; average peak fecal level was 137.1 micrograms/g in 24 hours. Fecal recoveries were 2.32 to 36.90% in 5 days after dosing with an average of 13.83%. 2. Urinary levels of the drug reached their peaks within 24 hours (average 51.46 micrograms/ml) in all cases and then decreased. Urinary recoveries were 11.15 to 46.44% in 5 days after dosing. Both fecal and urinary levels of the drug varied greatly among the subjects. 3. The sum of the fecal and the urinary recoveries in each case varied from 13.47 to 76.88% (average 42.24%).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1987

Analysis of protein C by using fascinating monoclonal antibodies against protein C.

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Antibodies, Monoclonal↗

PubMed1987

Effect of the intermittent prophylactic treatment of the central nervous system in adults with acute leukemia.

Nineteen patients with acute leukemia, who achieved complete remission between January, 1980 and March, 1983, were given 10 mg of methotrexate (MTX) and 20 mg of prednisolone (PSL) intrathecally at 1st, 3rd, 6th, 10th and 15th month after the termination of consolidation therapy followed by the same dose twice a year, when the intensification therapy was being performed. During the observation period of 29 to 68 months, none developed central nervous system (CNS) leukemia. On the other hand, the incidence of CNS leukemia in patients given the prophylactic intrathecal treatment once or twice just after the complete remission was 35% (7/20) compared with 24% (8/33) in patients without treatment. No statistical difference was observed in these groups. The intrathecal administration of MTX and PSL is easy to perform and no adverse reaction was observed in our series. It is concluded that the intermittent prophylaxis with MTX and PSL is of benefit in preventing CNS leukemia in adults patients with acute leukemia.

Acute Disease↗

PubMed1987

Level of protein C determined by combined assays during disseminated intravascular coagulation and oral anticoagulation.

We have developed a variation of the solid-phase enzyme-linked immunosorbent assay (ELISA) to enable measurement of the activity and antigen levels of protein C (PC) in human plasma. With this assay it is possible to do both tests with the same sample and same microtiter plate coated with anti-PC monoclonal antibody (MCA)JTC-4, which inhibited neither activation of PC nor activity of activated PC (APC). Even in patients undergoing heparin treatment for severe disseminated intravascular coagulation, there were no detectable differences between amidolytic activity and antigen levels of PC in patients' plasma. In addition, there was a strong correlation between the immunologic levels of PC in patients' plasma determined both by polyclonal ELISA using peroxidase-labeled immunopurified antiprotein C-IgG and those found with MCA ELISA using peroxidase-labeled MCAJTC-5, which does not bind to APC. In contrast, when oral anticoagulation therapy was started, immunologic levels of plasma PC estimated by peroxidase-labeled MCAJTC-1, a MCA that recognizes a gamma-carboxyglutamic acid domain-related conformational change of PC induced by metal ions, decreased more rapidly than did either the PC level determined by polyclonal ELISA or the percent prothrombin time. This suggested that comparison of MCAJTC-1-recognized PC levels and prothrombin time may be necessary at the beginning of oral anticoagulation therapy to treat patients safely.

Administration, Oral↗

PubMed1987

[My experience with an examination for a head nurse].

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Education, Nursing, Continuing↗

PubMed1987

[Pharmacokinetics of amikacin in children and neonates].

To evaluate pharmacokinetics of amikacin (AMK), one of the aminoglycoside antibiotics, children with ages from 2 days to 11 years were treated with various doses by various administration routes, and both plasma and urinary levels of AMK were determined. The following is a summary of the results obtained: 1. Of 6 children, three were treated with 2.0 mg/kg of AMK by a 30-minute intravenous drip infusion, and the other 3 with 4.0 mg/kg by a 60-minute. Peaks of average plasma levels were observed at the ends of the infusions in both cases, and their levels were 9.23 and 13.67 micrograms/ml, respectively, showing a dose-dependency. Both half-lives and areas under plasma concentration-time curves (AUCs) were similar to those of adults. However, the volume of distribution (Vd) showed a lower value than that of adults. Peaks of average urine levels were 149.3 micrograms/ml with 2.0 mg/kg in 0-2 hours after the start of the infusion and 223.3 micrograms/ml with 4.0 mg/kg in 2-4 hours. Average urinary recovery rates within 6 hours after the start of the infusion were 95.4% with 2.0 mg/kg and 85.7% with 4.0 mg/kg. These recoveries were equal to or higher than that of adults. 2. When 3.0, 4.0 and 6.0 mg/kg of AMK were administered to 3 groups of mature or premature babies by intramuscular injection, average peak levels of AMK in plasma were 6.26, 8.61 and 12.60 micrograms/ml, respectively, at 30 minutes after the injection, showing dose-dependency. In these groups, the younger the day age after birth was, the longer the half-life became. The AUCs were larger as the half-life became longer. The Vd was larger than that in the intravenous drip infusion group, but, any particular was not observed. Average peak levels of AMK in urine were 78.83 micrograms/ml at 4-6 hours with a dose level of 3.0 mg/kg, 99.17 micrograms/ml at 2-4 hours with 4.0 mg/kg and 139.20 micrograms/ml at 0-2 hours with 6.0 mg/kg. Average urinary recovery rates within 6 hours were 36.57% with 3.0 mg/kg, 34.67% with 4.0 mg/kg and 43.77% with 6.0 mg/kg. These recovery rates were markedly lower than those observed in adults and children. One of the causes of this low recovery is that mature and premature babies have immature renal functions. 3. When 3.0 mg/kg of AMK was administered to three premature babies by a 30-minute intravenous drip infusion, the average peak plasma levels was 7.61 micrograms/ml at the end of the drip infusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Amikacin↗

PubMed1987

[Effect of norfloxacin on bacterial flora in human feces].

Norfloxacin (NFLX), a synthetic oral antibacterial agent of quinolone carboxylic acid, was given orally for 5 full days at a dose of 200 mg, three times daily after each meal to healthy normal men with ages between 22 and 25 years weighing 53.0 to 84.0 kg (average 67.0 kg). The actual regimen followed was that the drug was administered twice after lunch and supper on the first day of dosing, and once after breakfast on the last day of dosing. On the 5th day before the start of dosing, on the first, 3rd and 5th days (last dosing day) of dosing, and on the 3rd, 5th, 10th and 20th days after the end of dosing, effects of the drug on the fecal flora were examined and its fecal levels were determined. Susceptibilities against NFLX and nalidixic acid (NA) of various fecal isolates from 7 men were determined. Adverse effects and influences on clinical laboratory tests were also examined. The results obtained are summarized below. 1. Following the drug administration, a transient decrease or disappearance of Escherichia coli, Klebsiella sp., Citrobacter sp. and Enterobacter sp. of Enterobacteriaceae was noted. The 3 strains other than E. coli were isolated from increasing number of cases after the end of dosing. No constant trend was observed in the isolation of Proteus sp. Organisms belong to Enterobacteriaceae were isolated only in 4 and 2 cases after 3 and 5 days of the start of dosing, respectively, but then gradually increased to the predose level. Among other Gram-negative bacteria, no constant trend was noted in the isolation frequency of Plesiomonas sp. Pseudomonas sp. was isolated from 6 and 5 cases on the 3rd day after dosing and on the 3rd day after the end of dosing, respectively; the frequency of isolation increased after dosing. Gram-positive bacteria such as Staphylococcus sp. were isolated with a reduced frequency on the 3rd day of dosing. However, the number of isolates increased in all cases both on the 5th day of dosing and on the 3rd day after the end of dosing, and then decreased. No change was noticed in the number of isolates of Enterococcus sp., and no constant trend was observed for Micrococcus sp. and YLO. The average count of the whole aerobic bacteria did not change. Some strains decreased significantly after the start of dosing. 2. Among anaerobes, Bacteroides fragilis and other Bacteroides were isolated on every test day.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1987

[A case of coarctation complex with left pulmonary artery hypertension after the treating by subclavian flapping and pulmonary artery banding].

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Aortic Coarctation↗

PubMed1986

Conformation-specific monoclonal antibodies to the calcium-induced structure of protein C.

Monoclonal antibodies to various domains of human protein C were characterized, and the cross-reactivity of these antibodies with other vitamin K-dependent proteins was explored. Three antibodies, JTC-1, -2, and -3 reacted with protein C only in the presence of Ca2+ and were shown to bind to the light chain of protein C. It is suggested that these antibodies recognize a gamma-carboxyglutamic acid domain-related conformational change induced by metal ions, evidenced by the fact that half-maximal binding was observed at calcium concentration of 0.5, 0.6, and 0.7 mM, respectively, by the fact that these antibodies, even in the presence of Ca2+, do not react with gamma-carboxyglutamic acid domainless protein C, and by the fact that Zn2+ and Tb3+ support binding in essentially the same way. Each cell line was stabilized by recloning five times. In addition each antibody had a single isoelectric point and was of the IgG1 kappa class. The interaction of antibodies JTC-1, -2; and -3 with protein C-Ca2+ was characterized by a single class of binding sites with Kd of 3.98 X 10(-9) M, 4.01 X 10(-9) M, and 6.76 X 10(-9) M, respectively. However, antibodies JTC-1, -2, and -3 bound to prothrombin-Ca2+ with Kd of 7.81 X 10(-9) M, 2.0 X 10(-7) M, and higher than 1.0 X 10(-5) M, respectively. In addition they had weak affinity for factor X in the presence of Ca2+. The results indicate that the antibodies JTC-1, -2, and -3 are conformation-specific monoclonal antibodies directed against an at least partially common metal ion-induced three-dimensional structure in protein C, prothrombin, and factor X.

Antibodies, Monoclonal↗

PubMed1986

Megakaryocytopoiesis in vitro of patients with essential thrombocythaemia: effect of plasma and serum on megakaryocytic colony formation.

To clarify the mechanism of increased numbers of megakaryocytes in patients with essential thrombocythaemia (ET), we studied in vitro megakaryocytopoiesis in ET and other myeloproliferative disorders, using a megakaryocytic colony assay in methylcellulose containing plasma or serum and medium conditioned by phytohaemagglutinin (PHA) stimulated leucocytes (PHA-LCM). Megakaryocytic colony formation was supported well by heparinized or citrated plasma and citrated serum which was harvested after clot formation of citrated plasma. Whole serum was inhibitory for megakaryocytic colony growth. The addition of platelet releasates and partially purified platelet derived growth factor (PDGF) resulted in a decrease in the number of megakaryocytic colonies. These findings suggested that platelet-derived factor(s) in serum was inhibitory to megakaryocytic colony formation. ET plasma supported the megakaryocytic colony formation by normal or ET bone marrow cells better than normal plasma. Moreover, in ET bone marrow cells, spontaneous megakaryocytic colonies were formed in the absence of PHA-LCM. Increased megakaryocytopoiesis in ET may be ascribed to (i) increased megakaryocyte-colony stimulating activity (Meg-CSA) in plasma and (ii) increased sensitivity to Meg-CSA or autonomous proliferation of megakaryocytic progenitor cells.

Adult↗

PubMed1986

Stimulation of ventromedial hypothalamus induces cold defense responses in conscious rabbits.

The involvement of the ventromedial hypothalamus (VMH) in thermoregulatory responses, which include heat production and heat loss responses, was investigated by the method of electrical stimulation. Electrical stimulation of the VMH caused a rise in rectal temperature, accompanied by the enhancement of heat production: O2 consumption and shivering. In addition, a reduction in heat loss was observed, including decreases in skin temperature (Ts), respiratory rate, and body surface area resulting from a huddled posture. In this study, stimulation of the lateral hypothalamus and other regions near the VMH had no effect on thermoregulatory responses. beta-Blocker (propranolol, 1 mg/kg iv) injected 20 min before stimulation lessened O2 consumption by approximately 10% and attenuated the reduction in Ts during VMH stimulation, whereas alpha-blockade (phentolamine, 1 mg/kg iv) was ineffective. These results indicate that most of the increase in O2 consumption during VMH stimulation was due to the occurrence of shivering but that some component of it could be due to nonshivering thermogenesis. They also indicate that the VMH, either directly or by converging influences, is involved in the activation of thermoregulatory responses to cold stress.

Adrenergic beta-Antagonists↗

PubMed1986

Rat endogenous pyrogen and fever.

Rat endogenous pyrogen (EP), prepared from the white blood cells of lipopolysaccharide-pretreated rats, produced a fever in both rabbits and rats. The effects of human, rabbit, and rat EP on the body temperatures of rabbits and rats were investigated to clarify differences in the febrile response to each kind of EP. The latency to fever onset and the time to peak fever induced by rat EP in rabbits and rats were significantly greater than those induced by human and rabbit EP. The maximum elevation of the body temperature induced by rat EP in both animals was almost identical to that induced by human and rabbit EP. In a comparison of the febrile responses to various EPs between rabbits and rats, the latency to fever onset, the time to peak, and the maximum elevation of fever in rats were approximately half those observed for rabbits. Furthermore, the threshold dosage to induce a fever response in rats was greater than that necessary for rabbits. It is concluded that rat EP could be obtained by in vitro techniques and that rats have the physiological mechanisms to develop a fever through production of EP.

Animals↗

PubMed1986

Mechanism of protein C-dependent clot lysis: role of plasminogen activator inhibitor.

The mechanism by which activated protein C stimulates fibrinolysis was studied in a simple radiolabeled clot lysis assay system containing purified tissue-type plasminogen activator, bovine endothelial plasminogen activator inhibitor (PAI), plasminogen, 125I-fibrinogen and thrombin. Fibrinolysis was greatly enhanced by the addition of purified bovine activated protein C; however, in the absence of PAI, activated protein C did not stimulate clot lysis, thus implicating this inhibitor in the mechanism. In clot lysis assay systems containing washed human platelets as a source of PAI, bovine-activated protein C-dependent fibrinolysis was associated with a marked decrease in PAI activity as detected using reverse fibrin autography. Bovine-activated protein C also decreased PAI activity of whole blood and of serum. In contrast to the bovine molecule, human-activated protein C was much less profibrinolytic in these clot lysis assay systems and much less potent in causing the neutralization of PAI. This species specificity of activated protein C in clot lysis assays reflect the known in vivo profibrinolytic species specificity. When purified bovine-activated protein C was mixed with purified PAI, complex formation was demonstrated using immunoblotting techniques after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. These observations suggest that a major mechanism for bovine protein C-dependent fibrinolysis in in vitro clot lysis assays involves a direct neutralization of PAI by activated protein C.

Blood Platelets↗