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Biomedical subjects

K Numata

Publications and source records attributed to K Numata.

At least 91 records · Page 5Linked to original sources

Effects of isoflurane and fentanyl on ischemic myocardium in dogs: assessment by end-systolic measurements.

The effect of anesthetics on ischemic myocardium to which blood was supplied by a stenotic coronary artery was investigated in dogs. The ischemia was assessed by regional wall motion (ultrasonic dimension technique) using fractional shortening (FS) [(EDL - ESL)/EDL x 100] and end-systolic pressure-segment length relationships (ESPLR). The latter is considered to be a more load-independent measure of regional myocardial function. Isoflurane and fentanyl were chosen as anesthetics of current interest. On reducing the left circumflex coronary artery (LCX) flow to approximately 50% of its resting value, a decrease in FS and a rightward shift in ESPLR were observed in myocardium perfused by the LCX. Simultaneously, increases in FS were observed in the nonischemic area perfused by the left anterior descending coronary artery (LAD), which was most likely due to the intraventricular unloading effect. No significant changes of ESPLR were observed in the area supplied by LAD. Isoflurane induced a dose-dependent decrease in FS and a rightward shift in ESPLR in the ischemic myocardial segment, whereas fentanyl caused an increase in FS and tended to shift ESPLR leftward in the same area. The results suggest that isoflurane may have deleterious effects on preexisting myocardial ischemia, whereas fentanyl may not when loading conditions are taken into consideration. Fractional shortening and ESPLR seem to provide similar information about regional myocardial function.

Anesthesia, Inhalation↗

[Usefulness of recombinant human erythropoietin in cardiac surgery with autologous blood transfusion].

The efficacy and method of administration of recombinant human erythropoietin (EPO) in adult cardiac surgical patients when given preoperatively was evaluated. We used EPO intravenously (iv) with 40 mg ferric oxide for a total of consecutive 47 patients. The patients were divided into group A (n = 14; EPO 200 IU/kg iv 3 times a week from 3 weeks prior to surgery to 2 weeks after surgery, donation of 800 ml) and group B (n = 33; EPO 200 IU/kg iv everyday from 8 days prior to surgery to 2 weeks after surgery, donation of 400 ml). Control groups were group AO (n = 11; donation of 835 +/- 33 ml from 14.8 days prior to surgery) and group BO (n = 7; donation of 406 +/- 34 ml at 7.3 days prior to surgery). All the EPO-treated patients received no homologous blood transfusion while 2 of patients in group BO received some homologous blood transfusion. A hemoglobin change between pre-donation and surgery was +0.14 +/- 1.3 (g/dl) in group A, +0.04 +/- 1.0 (g/dl) in group B, -1.7 +/- 1.3 (g/dl) in group AO and -1.0 +/- 0.6 (g/dl) in group BO. In a comparison of post-surgical hemoglobin levels between group A and group B, we demonstrated that the level in group B, +2.1 +/- 1.8 (g/dl) was significantly higher than that in group A, +11.1 +/- 1.6 (g/dl) 2 weeks after surgery. There was no evidence to show an aggravation of anemia in the pre-surgical period in EPO-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗

Very-low-calorie diet-induced weight reduction reverses impaired growth hormone secretion response to growth hormone-releasing hormone, arginine, and L-dopa in obesity.

To determine whether impaired growth hormone (GH) secretion in obese subjects is a consequence of obesity or a pre-existing pituitary-hypothalamic disorder, we measured (1) plasma GH response to growth hormone-releasing hormone (GRH; 1 microgram/kg body weight [BW]), arginine (0.5 g/kg BW), and L-dopa (500 mg); and (2) plasma glucose, insulin, and free fatty acids (FFA) in obese subjects before and after weight reduction due to very-low-calorie diet therapy using Optifast (240 kcal/d for 8 to 12 weeks). Body weight and body mass index (BMI) values before and after weight reduction were 87.2 +/- 4.1 kg and 34.5 +/- 0.9 kg/m2, and 67.8 +/- 2.7 kg and 27.0 +/- 0.4 kg/m2, respectively. GH response to GRH, arginine, and L-dopa in obese subjects was markedly impaired before weight reduction, whereas significantly increased responses were noted after weight reduction (P less than .01). Impaired integrated GH response to GRH, arginine, and L-dopa in obese subjects was significantly restored after weight reduction (P less than .01). Plasma glucose levels did not change, while plasma insulin and FFA levels decreased significantly after weight reduction (P less than .01, P less than .05). There was no significant correlation between integrated GH response to these three stimuli and plasma levels of glucose, insulin, and FFA, respectively. The reversibility of GH response to all three stimuli after weight reduction suggests that impaired GH secretion is a consequence of obesity rather than a pre-existing pituitary-hypothalamic disorder.

Adolescent↗

The susceptibility of Campylobacter pylori to antiulcer agents and antibiotics.

The antibacterial activities of antiulcer agents and antibiotics against Campylobacter pylori were studied. The MIC90 values of three kinds of antibiotics--macrolides, beta-lactams, and metronidazole--were 0.05-0.78, 0.39-1.56, and 12.5 micrograms/ml, respectively. They were more active than antiulcer agents such as H2-blockers and cetraxate with MIC90 values of greater than or equal to 1,600 and greater than 1,600 micrograms/ml, respectively. Especially, clarithromycin, a new derivative of erythromycin, showed an MIC90 of 0.05 microgram/ml. However, the other antiulcer agents such as sofalcone and tripotassium dicitrate bismuthate (TDB) also had MIC90 values of 50 and 6.25 micrograms/ml, respectively. Clarithromycin, sofalcone, and TDB showed bactericidal activity against C. pylori CLO2. The bactericidal actions of these drugs could be observed under electron microscopy.

Anti-Bacterial Agents↗

Chemical modification of erythromycins. III. In vitro and in vivo antibacterial activities of new semisynthetic 6-O-methylerythromycins A, TE-031 (clarithromycin) and TE-032.

The in vitro and in vivo antibacterial activities of 6-O-methylerythromycin A (TE-031, A-56268, or clarithromycin) and 6,11-di-O-methylerythromycin A (TE-032) have been compared with those of erythromycin A (EM) and josamycin (JM). TE-031 and TE-032, having the same antibacterial spectra as EM, are active against aerobic Gram-positive bacteria, some Gram-negative bacteria, anaerobic bacteria, L-form bacteria and Mycoplasma pneumoniae. The activity of TE-031 against clinical isolates is equal to or two times more potent than that of EM, whereas TE-032 is slightly less active than EM. The activities of TE-031 and TE-032 are pH dependent (more active at pH 8 than at 5) and are increased by adding serum to medium. TE-031 and TE-032 show dose-related bactericidal activities against Haemophilus influenzae. The therapeutic efficacies of TE-031 and TE-032 against systemic and subcutaneous infections provoked by Gram-positive bacteria in mice are 4- to 35-fold superior to those of EM and JM. TE-031 and TE-032 have demonstrated higher and longer-lasting plasma levels than EM when administered orally to mice, rats or dogs.

Animals↗

Calcium-dependent anticandidal action of pradimicin A.

Pradimicin A shows candicidal activity at 10 micrograms/ml in vitro. The action of pradimicin A on Candida albicans cells involves a set of specific cell surface interactions in a Ca2(+)-dependent manner. These include binding to the mannan components on the cell surface and subsequent interactions at the level of the plasma membrane, causing K+ leakage and cell death. The protoplasts prepared from C. albicans undergo lysis rapidly when treated with pradimicin A. These results suggest that pradimicin A acts primarily on the candidal plasma membrane, leading to a perturbation of membrane function.

Anthracyclines↗

Biochemical and histological findings on the effect of fibronectin in rabbits with experimental corneal disorders.

The effects of purified plasma fibronectin (FN) in corneal disorders were investigated. Histological findings, the levels of ascorbic acid (AA) and glutathione (GSH) in tear fluids were observed sequentially in rabbits with experimental corneal damage and the degree of corneal lesions was observed. The results indicated that healing of the tissue damage was more promoted in the FN group than in the controls and it was suggested that FN promoted the healing of corneal disorders.

Animals↗

[A pharmacodynamic analysis of the onset of neuromuscular blockade by nondepolarizing muscle relaxants--the pharmacodynamics of a large dose of vecuronium].

From Sheiner's equation on pharmacokinetics and pharmacodynamics, we derived a new equation which described the pharmacodynamics of nondepolarizing muscle relaxants during the onset phase. This equation showed that log (l0/l-1) had a linear relation to log (t) where "t" is the time after the administration of nondepolarizing muscle relaxant and "l" and "l0" are the twitch height at t = t and t = 0 respectively. It also implies that the administration dose (D) is inversely proportional to the onset time (OT), i.e., D.OT = const. We proved that these two relations held well for the actual 7 cases of vecuronium use in man. In conclusion, when vecuronium dose level was within 0.15-0.30 mg.kg-1 i.v., the dose was inversely proportional to the onset time which was defined as the time interval from the end of the administration of vecuronium until the single twitch was depressed under 5% of control value, i.e., Dose (mg.kg-1) x onset-time (sec) not equal to 24. During anesthesia with enflurane as well as during neuroleptanesthesia, a dose of vecuronium 0.3 mg.kg-1 (n = 7) was found to produce a duration of neuromuscular blocking action equal to the mean duration produced by pancuronium 0.1 mg.kg-1.

Adult↗

[Comparative pharmacokinetics of pipecuronium bromide, pancuronium bromide and vecuronium bromide in anesthetized man].

The pharmacokinetics of pipecuronium bromide was studied in 9 male patients (ASA class 1-2, 20-65 years of age). Following a single intravenous dose of pipecuronium 0.08 mg.kg-1, plasma levels were measured by capillary gas chromatography. Plasma concentration-time curves were evaluated by fitting the data to a bi-exponential equation. The pharmacokinetic parameters of pipecuronium were compared with those of pancuronium (0.08 mg.kg-1) and vecuronium (0.08 mg.kg-1) previously obtained under the same anesthesia (66% N2O, 33% O2 and 1% halothane). With pipecuronium, following pharmacokinetic parameters were obtained; distribution half-life; T1/2 alpha = 3.9 +/- 0.7 min (mean +/- SEM), elimination half-life; T1/2 beta = 102 +/- 12 min, volume of the central compartment; V1 = 95 +/- 13 ml.kg-1, volume of distribution at steady state; Vdss = 264 +/- 41 ml.kg-1, clearance; Cl = 1.8 +/- 0.2 ml.min-1.kg-1. Microconstants of two-compartment open models (k12, k21, k10) were also calculated. Using Mann-Whitney's U-test, these parameters of pipecuronium were compared with those of pancuronium (n = 3) and vecuronium (n = 4). V1 and Vdss of pipecuronium were significantly larger than those of pancuronium (V1; 38 +/- 12 ml.kg-1 and Vdss; 120 +/- 4 ml.kg-1) (both P less than 0.10). Reflecting the larger central volume of pipecuronium, pipecuronium tended to have a larger clearance than that of pancuroniumu (Cl; 1.1 +/- 0.2 ml.min-1.kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Evaluation of the action of pipecuronium bromide in patients under halothane anesthesia--a comparison with pancuronium bromide regarding their neuromuscular blocking and cardiovascular effects].

Neuromuscular blocking and circulatory actions of pipecuronium bromide (PPB) were evaluated in patients under halothane-nitrous oxide-oxygen anesthesia in comparison with those of pancuronium bromide (PCB) in a multi-center cooperative study. Twitch tension of the adductor pollicis muscle was elicited by supramaximal stimulation of the ulnar nerve every 10 seconds. The study was performed according to the following 4 steps and the results were obtained. 1) Cumulative administration of 0.01 mg.kg-1 of PPB or PCB resulted in the potency ratio of 1.3:1.0 and the dose response curves of the two agents paralleled with each other. 2) With PPB 0.05 mg.kg-1 or 0.1 mg.kg-1, almost 100% block of the twitch was obtained. Both duration of action and the recovery time were shorter with 0.05 mg.kg-1 group. 3) After the first dose of 0.04 mg.kg-1 when the twitch recovered to 25% of the initial height 0.02 mg.kg-1 was given and this was repeated. Intervals between the doses showed large individual differences and no significant change was observed with repeated doses. 4) Safety of the drug. No significant change in heart rate or blood pressure was observed with PPB but with PCB a significant increase in heart rate was observed. The study revealed that PPB is slightly more potent than PCB and the duration of action is longer, but it has no untoward cardiovascular action in man under halothane anesthesia.

Adult↗

[A case of delayed radiation lumbo-sacral plexopathy].

We report a 47-year-old woman who developed a slowly progressive lumbosacral plexopathy with mixed sensorimotor losses in the lower extremities. The symptoms were apparent 8 years after x-ray irradiation for an ovarian carcinoma. Neurological examination showed mild weakness and absent deep tendon reflexes of bilateral lower extremities, and hypesthesia to all modalities in anterior aspects of bilateral lower thighs, in dorsum pedis and soles. Extensive investigations regarding the possibility of tumor recurrence were negative. Computed tomography of pelvis showed abnormal soft tissue densities around the lumbosacral plexus. Intravenous pyelography showed bilateral hydronephrosis and narrowed ureters at the first sacral vertebra level. These findings are consistent with radiation-induced fibrosis rather than tumor infiltration. The results suggest the entrapment lumbosacral plexopathy due to surrounding fibrosis after irradiation. We speculated the sensorimotor losses caused by entrapment of the lumbosacral plexus.

Female↗

[A benzodiazepine antagonist flumazenil in clinical use--a dose finding study].

The effective dose, usefulness and side effects of flumazenil, a specific benzodiazepine antagonist, have been investigated in 72 sleeping patients after the end of the surgical operation who had received flunitrazepam 0.03 mg.kg-1, a long acting benzodiazepine. The patients received intravenous injections of flumazenil 0.1 mg, 0.2 mg, 0.4 mg and 0.8 mg per person as initial doses. Four minutes after the injection of flumazenil, the percentages of the patients who were awake, were 47.4% in 0.1 mg group, 82.4% in 0.2 mg group, 82.4% in 0.4 mg group and 88.2% in 0.8 mg group respectively. There were several side effects observed in all the groups except 0.2 mg group. However, they presented no clinical problems. Therefore, flumazenil 0.2 mg as the initial dose, is considered appropriate.

Adolescent↗

[Effect of induced hypotension on arterial blood ketone body ratio (AKBR)].

Arterial blood ketone body ratio (AKBR; acetoacetate/beta-hydroxybutyrate) is known as a parameter to indicate the function of the liver cells. We evaluated the effects of induced hypotension with prostaglandin E1 (PGE1) or trimetaphan (TMP) on AKBR in patients without liver disease undergoing mastectomy. Almost no change was observed in AKBR before, during and after hypotension with PGE1, but slight diminution was observed during hypotension with TMP. No hepatic dysfunction, however, developed in these patients postoperatively. These findings suggest that usual hypotension with TMP may provoke no postoperative hepatic dysfunction in patients without liver disease. For the patient who required either hypotension of long duration or hypotension with other factors affecting function of liver (surgical procedures, drugs and others), we prefer PGE1 to TMP as a hypotensive drug. We should also adopt PGE1 when cardiovascular control with hypotensive drug is necessary in patients with liver disease.

Alprostadil↗

Phasic capillary pressure determined by arterial occlusion in intact dog lung lobes.

In six open-chest dogs, electrocardiogram- (ECG) controlled pulmonary arterial occlusion was performed during the control period and during the infusions of serotonin and histamine. A temporal series of instantaneous pulmonary capillary pressure and the longitudinal distributions of vascular resistance and compliance were evaluated in the intact left lower lung lobe. In the control period, we found a significant phasic variation of pulmonary capillary pressure (Pc) with the cardiac cycle. The ratio of arterial to venous resistances (Ra/Rv) was 6:4, and the ratio of arterial to capillary compliances (Ca/Cc) was 1:11. During the infusions of serotonin and histamine, Pc showed similar phasic variations, despite significant hemodynamic changes induced by these agents. Serotonin predominantly increased Ra, whereas histamine predominantly increased Rv. The ratio of Rv to the total resistance decreased significantly from 0.42 to 0.32 during the infusion of serotonin and increased significantly to 0.62 during the infusion of histamine. The data suggest that phasic Pc determined by ECG-controlled arterial occlusion reflects the pulsatility in the pulmonary microvascular bed under control conditions and after alterations of the pulmonary vascular resistance by serotonin and histamine.

Animals↗

Cispentacin, a new antifungal antibiotic. II. In vitro and in vivo antifungal activities.

Cispentacin [-)-(1R,2S)-2-aminocyclopentane-1-carboxylic acid) is a new antifungal antibiotic possessing potent anti-Candida activity. The 50% inhibitory concentration (IC50) and IC100 values of cispentacin against clinical isolates of Candida albicans were in the ranges 6.3 approximately 12.5 and 6.3 approximately 50 micrograms/ml, respectively, by turbidimetric measurement in yeast nitrogen base glucose medium. No significant activity was seen against any yeasts and molds when tested by the agar dilution method using three different agar media: KNOPP's agar, yeast extract-glucose-peptone agar and Sabouraud dextrose agar. This antibiotic demonstrated good therapeutic efficacy against a systemic Candida infection in mice by both parenteral and po administrations. The 50% protection dose (PD50) values after single iv and po administrations were 10 and 30 mg/kg, respectively. It was also effective in a systemic infection with Cryptococcus neoformans and in both lung and vaginal infections with C. albicans in mice. Cispentacin did not induce acute lethal toxicity at 1,000 mg/kg by iv injection and 1,500 mg/kg by ip and po administrations in mice.

Amphotericin B↗