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Biomedical subjects

K Numata

Publications and source records attributed to K Numata.

At least 55 records · Page 3Linked to original sources

[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

[Periodic sublingual buprenorphine for pain relief after upper abdominal surgery].

Analgesic effects were evaluated in patients who received sublingual administration of buprenorphine (0.2mg ampule for injection) as programmed every 8 hours for 3 days following upper abdominal surgery. Patients who received periodic sublingual buprenorphine obtained satisfactory postoperative analgesia and also required less analgesics than those who never received periodic administration of analgesics. Approximately one half of patients who received periodic sublingual buprenorphine required no additional analgesics. Arterial blood-gas analysis showed a significant increase in carbon dioxide tension after sublingual buprenorphine. One patient revealed marked respiratory acidosis after sublingual buprenorphine. These results suggest that periodic sublingual buprenorphine makes up for slow onset in sublingual administration and that it is also effective, convenient, and safe for pain relief after upper abdominal surgery. We, however, should pay attention to the respiratory depression caused by sublingual buprenorphine.

Abdomen

[Comparison of O2 saturation measurements by oximetry and by gas analysis].

For checking the reliability of pulse oximetry in the operating rooms, we compared values of arterial O2 saturation measured by a blood gas analyzer (SAT) with values monitored by pulse oximetry (SaO2). SaO2's were found to be significantly different from SAT's. The regression equation was SAT = 0.31 X SaO2 + 68.4 and the correlation coefficient was 0.66. P value of paired comparison was 0.0001 indicating that the two sets of values were not equal to each other. When one observer performed a similar study using a high-fidelity pulse oximeter, SaO2's were not different from SAT's. The regression equation in this case was SAT = 0.85 X SaO2 + 15.0 and the correlation coefficient was 0.95. P value of paired comparison was 0.3244. The reliability of pulse oximetry differs from one anesthesiologist to another and depends upon the accuracy of each pulse oximeter. In clinical experiment, using the data by pulse oximetry in operating room is misleading.

Blood Gas Analysis

Glidobactins A, B and C, new antitumor antibiotics. II. Structure elucidation.

The structures of new antitumor antibiotics, glidobactins A (Ia), B (Ib) and C (Ic) were elucidated by a combination of chemical and enzymatic degradations and spectral analyses. They have in common a cyclized tripeptide nucleus composed of L-threonine, 4(S)-amino-2(E)-pentenoic acid and erythro-4-hydroxy-L-lysine, and differ from each other in the unsaturated fatty acid moiety attached to the peptide.

Amino Acids

Enzymatic formation of glidobactamine: a peptide nucleus of glidobactins A, B and C, new lipopeptide antitumor antibiotics.

Glidobactin deacylating activity was found in a bacterial strain of Pseudomonas sp. Glidobactamine, a key intermediate for acyl analogues of glidobactin, was isolated from the enzymatic degradation products of glidobactins after treatment using a column of fibrous active gel on which the cells of the Pseudomonas strain were immobilized. The chemical structure of glidobactamine was confirmed as the intact peptide moiety of glidobactins by chemical reformation of glidobactin A from glidobactamine and 2,4-dodecadienoic acid which is the constitutive fatty acid of glidobactin A.

Antibiotics, Antineoplastic

Enhanced production of the minor components of glidobactins in Polyangium brachysporum.

Polyangium brachysporum sp. nov. strain ATCC 53080 produces a novel type of antifungal and antitumor antibiotic complex, glidobactins A, B and C. Enhanced production of minor components, glidobactins B and C, was achieved by medium modification. The addition of soybean oil or corn oil, which are rich in unsaturated C18 fatty acids, to the fermentation medium led to an increased production of components B and C. Productivity of component C was selectively enhanced by the addition of oleic acid-rich oils, olive oil and Tween 80 (polyoxyethylene sorbitan mono-oleate). Furthermore, precursing palmitoleate, linoleate and oleate permitted the direct biosynthesis of components A, B and C, respectively. The fermentation with 3% addition of an appropriate oil at initial time provided an optimal production of component B or C.

Antibiotics, Antineoplastic

Chemical modification of the antitumor antibiotic glidobactin.

A variety of glidobactin analogs modified at the fatty acid, L-threonine and nucleus moieties of the molecule were synthesized and their structure-activity relationships examined. The antitumor and antifungal activity was greatly influenced by modification of the fatty acid glidobactin, with the dodecanoyl and tetradecanoyl analogs exhibiting better antitumor activity than the parent antibiotics. Replacement of the L-threonine with other amino acids greatly reduced the activity and reduction of the double bond of the nucleus completely eliminated the biological activity of glidobactin.

Antibiotics, Antineoplastic