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Biomedical subjects

K Mikawa

Publications and source records attributed to K Mikawa.

At least 109 records · Page 6Linked to original sources
PubMed1995

Role of G proteins and KCa channels in the muscarinic and beta-adrenergic regulation of airway smooth muscle.

We have examined the functional consequences of G protein coupling to calcium-activated potassium (KCa) channels using isometric tension records from guinea pig tracheal smooth muscle. After incubation with 1 microgram/ml pertussis toxin (PTX) for 6 h, the contraction response to 1 microM methacholine (MCh) was suppressed by 31.7 +/- 5.0% (n = 10). Similarly, the contraction was inhibited by 29.1 +/- 5.0% (n = 6) after application of 0.1 microM AF-DX 116, an M2-selective muscarinic receptor antagonist. Cholera toxin (CTX, 2.0 micrograms/ml for 6 h), which activates the stimulatory G protein of adenylyl cyclase (Gs), also suppressed contraction by 43.9 +/- 3.3% (n = 11). The inhibitory effects of PTX, AF-DX 116, or CTX were reversed in the presence of 100 nM charybdotoxin (ChTX), a selective KCa channel inhibitor. These findings suggest that disruption of inhibitory coupling between muscarinic receptor and KCa channels mediated by PTX-sensitive G proteins, or KCa channel activation induced by Gs/adenylyl cyclase-linked processes, antagonizes muscarinic contraction. The isoproterenol concentration-inhibition curves for precontracted trachea (1 microM MCh) were shifted to the left after perfusion with PTX or AF-DX 116, and the leftward shift of the curve was blocked by ChTX. Thus direct or indirect regulation of KCa channels mediated by the inhibitory guanine nucleotide binding protein (Gi) and Gs may play a functionally important role in the mechanical antagonism by the two receptor agonists.

Adenylate Cyclase Toxin↗
PubMed1994

Improvement of gas exchange following endobronchial instillation of an exogenous surfactant in an infant with respiratory failure by postoperative pulmonary haemorrhage.

We administered surfactant to a 5-month-old infant with respiratory failure due to right pulmonary haemorrhage accompanied by oedema following abdominal surgery. These pathological conditions were probably precipitated by disseminated intravascular coagulation and intra-operative excessive administration of fluids, respectively. Endobronchial instillation of the exogenous surfactant (120 mg) after selective intubation of the right bronchus produced a dramatic improvement of gas exchange 30 min after treatment and of chest X-ray findings at 6 h post-treatment. This case on an infant indicates that administration of surfactant may be one of promising therapeutic approaches to respiratory failure due to pulmonary haemorrhage.

Biliary Atresia↗
PubMed1994

Omeprazole reduces preoperative gastric fluid acidity and volume in children.

To explore the effects of oral omeprazole on preoperative gastric fluid pH and volume in children, 104 healthy in-patients aged 4-9 yr were randomly allocated to four groups (n = 26). Subjects in the Omeprazole-Omeprazole Group received two doses of omeprazole (20 mg per dose), those in the Placebo-Placebo Group, two doses of placebo, those in the Placebo-Omeprazole and Omeprazole-Placebo Groups, one dose each of the two preparations by mouth. For each treatment regimen, the first medication was administered at 9:00 p.m. on the night before surgery and the second at 5:30 a.m. on the morning of the day of surgery (three hours preoperatively). Children undergoing elective surgery were offered 10 ml.kg-1 of apple juice three hours before induction of anaesthesia. After induction of anaesthesia and tracheal intubation, gastric fluid was aspirated through a large-bore, multiorifice orogastric tube and analyzed for pH and total fluid volume. The administration of omeprazole at bedtime before surgery increased gastric pH (3.3 +/- 1.3 vs 2.0 +/- 0.6, P < 0.05) in comparison with placebo, as did two doses of omeprazole (pH = 4.8 +/- 1.6, P < 0.05). A single dose of omeprazole administration on the morning of the day of surgery failed to increase gastric pH. There was a reduction in the number of children with a pH < 2.5 and a volume > 0.4 ml.kg-1 in the Omeprazole-Omeprazole and Omeprazole-Placebo Groups, compared with the Placebo-Placebo or Placebo-Omeprazole Groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Inhibitory effect of prostaglandin E1 on human neutrophil function.

Neutrophils accumulated in the lung are thought to play a pivotal role in the pathogenesis of host auto-injury such as adult respiratory distress syndrome (ARDS). We investigated the effect of prostaglandin E1 (PGE1) on several aspects of human neutrophil function. PGE1 significantly decreased reactive oxygen species (ROS), (O2-, H2O2, OH.) generation by neutrophils as well as neutrophil phagocytosis and chemotaxis. In contrast, the drug did not affect the levels of ROS generated by a cell-free ROS generating system. In addition, intracellular calcium concentrations ([Ca2+]i) in neutrophils stimulated by f-Met-Leu-Phe were decreased in the presence of PGE1. These data suggest that the reduction in ROS production and neutrophil phagocytosis and chemotaxis by PGE1 may contribute to the effectiveness of the drug in host auto-injury including ARDS. The suppression of the increase in [Ca2+]i may at least be responsible for inhibition of these neutrophil functions by PGE1.

Adult↗
PubMed1994

Effects of oral nizatidine on preoperative gastric fluid pH and volume in children.

We have studied the effect of oral nizatidine 6 mg kg-1 in total on preoperative gastric fluid pH and volume in children. One hundred and four healthy children, aged 4-11 yr, were allocated randomly to four groups (n = 26): placebo administered at 21:00 and 06:30 the night before and on the day of surgery, respectively (placebo-placebo: control); nizatidine 6 mg kg-1 at 21:00 and placebo at 06:30 (nizatidine-placebo); placebo at 21:00 and nizatidine 6 mg kg-1 at 06:30 (placebo-nizatidine); and nizatidine 3 mg kg-1 at 21:00 and 06:30 (nizatidine-nizatidine). Each child ingested a large volume of apple juice 3 h before estimated induction of anaesthesia. After induction of anaesthesia, pH and volume of gastric fluid obtained via an orogastric tube were measured. Mean pH in the placebo-nizatidine and nizatidine-nizatidine groups was significantly higher than that in the placebo-placebo group (5.7 (SEM 0.3), 6.0 (0.3) vs 1.8 (0.2), respectively) (P < 0.05). Mean pH in the nizatidine-placebo group was similar to that in the control group (2.3 (0.3) vs 1.8 (0.2)). The number of children with pH < 2.5 and volume > 0.4 ml kg-1 in the nizatidine-nizatidine (0%) and placebo-nizatidine (4%) groups was reduced compared with the control (46%) or nizatidine-placebo (38%) group.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Effect of lidocaine pretreatment on endotoxin-induced lung injury in rabbits.

BACKGROUND: It is well known that endotoxin causes acute lung injury resulting in adult respiratory distress syndrome. Numerous cellular and humoral factors such as macrophages, neutrophils, platelets, and inflammatory mediators (e.g., activated complements, cytokines, and arachidonic acid metabolites) are thought to play a pivotal role in the pathogenesis of endotoxin-induced lung injury. Furthermore, pulmonary edema in acute lung injury is associated with an increase in vascular permeability that may arise from a perturbation of the endothelial cell surface membrane. Lidocaine has been shown to inhibit function of these cells and stabilize cell membranes. The aim of the current study was to determine whether pretreatment with intravenous lidocaine could attenuate acute lung injury induced by endotoxin in rabbits. METHODS: Twenty-seven anesthetized male rabbits were randomly assigned to receive one of three treatments (n = 9 for each group); infusion of saline (as a control), infusion of Escherichia coli endotoxin (30 micrograms kg-1 over a 60-min period) without treatment with lidocaine, and infusion of endotoxin with treatment with lidocaine. A single dose of intravenous lidocaine 2 mg.kg-1 was administered 10 min before infusion of endotoxin and thereafter infused at a rate of 2 mg.kg-1.h-1 until 6 h after the start of endotoxin administration, when the animals were killed. The lungs of the rabbits were ventilated with 40% oxygen. Hemodynamics, peripheral leukocytes counts, and arterial oxygen tension were recorded during the ventilation period. After the observation, lung mechanics, cell fraction of bronchoalveolar lavage fluid (BALF), activated complements, cytokines, and arachidonic acid metabolites concentrations in BALF were measured and analyzed. The lung wet-to-dry-weight ratio and albumin concentrations in BALF were analyzed as an indices of pulmonary edema. The cypridina luciferin analog-dependent chemiluminescence (representing superoxide production) by neutrophils isolated from the pulmonary artery and light microscopic findings were compared among the three groups. RESULTS: Endotoxin caused decreases in peripheral leukocyte counts, lung compliance, and arterial oxygen tension, and increases in the lung wet-to dry-weight ratio, polymorphonuclear cell counts in BALF, and albumin, C3a, C5a, tumor necrosis factor alpha, interleukin-1 beta, and thromboxane B2 concentrations in BALF. Lidocaine pretreatment attenuated these changes. The cypridina luciferin analog--dependent chemiluminescence was greater in rabbits receiving endotoxin than in the control. Lidocaine pretreatment attenuated the increase in chemiluminescence. Endotoxin caused extensive morphologic lung damage, which was lessened by lidocaine. CONCLUSIONS: These results suggest that intravenous lidocaine pretreatment has a prophylactic effect on endotoxin-induced lung injury in rabbits. However, further studies are required to investigate the therapeutic (as an early posttreatment) effect of the drug given after lung injury because rabbits in the current study received lidocaine before endotoxemia.

Animals↗
PubMed1994

Partial attenuation of the cardiovascular responses to tracheal intubation with oral manidipine.

We conducted a placebo-controlled, randomized, and double-blinded study to evaluate the efficacy of manidipine given orally in attenuating the cardiovascular responses to laryngoscopy and tracheal intubation. Thirty normotensive patients (ASA physical status 1) undergoing elective surgery were allocated to one of three groups (n = 10 for each); placebo, 5 mg manidipine, and 10 mg manidipine groups. These tablets were orally administered 3 h before induction of anaesthesia. Anaesthesia was induced with thiopentone 5 mg.kg-1 iv, and tracheal intubation was facilitated with vecuronium 0.2 mg.kg-1. Laryngoscopy lasting 30 sec was attempted 2 min after induction of anaesthesia. Patients receiving placebo showed a significant increase in systolic and diastolic blood pressure associated with tracheal intubation. These increases following tracheal intubation were significantly reduced in patients receiving manidipine 10 mg compared with patients receiving placebo or manidipine 5 mg (P < 0.05). Oral administration of manidipine 10 mg before induction of anaesthesia is a simple and effective method for attenuating pressor response to laryngoscopy and tracheal intubation. We stressed that the potential beneficial effect of a reduced haemodynamic reaction to intubation might be obtained at the expense of hypotension later on.

Administration, Oral↗
PubMed1994

Clonidine decreases the dose of thiamylal required to induce anesthesia in children.

Clonidine is a useful drug to give preoperatively because it produces anxiolysis, sedation, and hemodynamic stability, and reduces intravenous and volatile anesthetic requirements. Several premedicants, including midazolam and diazepam, have been shown to reduce the induction dose of intravenous anesthetics, such as thiopental, ketamine, or propofol. A randomized, double-blind controlled study was conducted to evaluate the effect of premedication with oral clonidine on thiamylal requirement for the induction of anesthesia and on associated hemodynamic changes in children. Sixty children (ASA grades I-II, 7-12 yr old) were assigned randomly to receive one of three treatments (n = 20, for each group): placebo (control), clonidine 2 micrograms/kg, or clonidine 4 micrograms/kg 105 min before the induction of anesthesia. Thiamylal was injected at a dose of 1 mg/kg every 15 s until loss of the eyelash reflex and the dose was recorded. Blood pressure (BP), heart rate (HR), and arterial oxygen saturation were recorded every minute from the beginning of injection of thiamylal for 5 min. Significant decreases in thiamylal dose were observed in patients receiving clonidine. The induction dose of thiamylal (mean +/- SD) was 5.4 +/- 0.9, 4.5 +/- 1.1, and 3.4 +/- 0.9 mg/kg for patients receiving placebo, clonidine 2 micrograms/kg, and clonidine 4 micrograms/kg, respectively (P < 0.05). Systolic BP decreased by 6.8%, 5.6%, and 6.6% and HR increased by 5.7%, 4.8%, and 4.1% after administration of thiamylal in the control (placebo) group and the clonidine 2 micrograms/kg and clonidine 4 micrograms/kg groups, respectively (P > 0.05). Premedication with oral clonidine reduced the dose of intravenous thiamylal required for the induction of anesthesia in children.

Anesthesia, Intravenous↗
PubMed1994

[Assessment of quality of life after transurethral resection of prostate for benign prostatic hyperplasia].

The quality of life (QOL) after transurethral resection of the prostate (TURP) was studied. A total of 113 patients were operated and released, and 86 (76%) cases responded to the TURP follow-up survey. The average age was 69 years and the average time elapsed after the operation was 220 days. Data regarding the patients undergoing TURP was gathered from a questionnaire consisting of 22 questions concerning the preoperative condition and 28 about the post-operative state. Performance status was not changed post-TURP. The patients showed improvements in nocturia, pollakisuria and dysuria. These urological symptoms were in accordance with the findings of uroflowmetry and American Urological Association Symptom Index. Ten questions addressing the patients mental and physical conditions revealed that good quality was generally retained. Sexual activity showed a tendency of gradual decrease in relation to increasing age. Ejaculatory function and actual satisfaction with the sexual act were obviously damaged by the operation. TURP showed no changes in regard to morning erection, sexual desire in an arousing atmosphere, penile hardness at sex and total satisfaction with the sexual life. Social life, family life and mental status were not influenced, but the physical status of 21 (26%) of the patients was decreased by the operation and hospital stay. Over all, 78% of the patients could maintain a good quality of life in post-TURP.

Aged↗
PubMed1994

An INTERSALT study investigation: relationship between body mass index and blood pressure in the combined populations of three local centres in Japan.

Body mass index was positively and strongly correlated with BP in the INTERSALT study. Because the average body mass index in Japan, although low relative to other developed countries, has been increasing recently it would be useful, particularly from the public health viewpoint, to investigate the impact of body mass index on BP in Japanese populations. In this study, the relationship between body mass index and BP was investigated taking into account age, alcohol intake and sodium and potassium excretion in 24h urine. Data were obtained from 274 men and 284 women, aged 20-59 years, who were not taking antihypertensive medication. Random selection of participants took place at three local centres as outlined in the 1985 INTERSALT study in Japan. It was found that body mass index was positively and significantly correlated with BP in men and women, respectively, but was independent of age, alcohol intake and urinary sodium/potassium ratio. Both SBP and DBP were significantly higher by > or = 5 mmHg in participants whose body mass index (kg/m2) was in the highest quartile compared with participants in the lowest or the next lowest quartile category in men and women. In this study, it was suggested that the body mass index in Japanese men and women was directly correlated with BP independent of other confounding factors. Accordingly, the maintenance of a moderate body mass index may be important in achieving and maintaining a desirable BP level.

Adult↗
PubMed1993

Perioperative changes in superoxide production in neonates and infants.

We conducted a prospective study to investigate perioperative changes in the production of superoxide anion (O2-) by neutrophils isolated from ten neonates between the ages of five and 16 days (N group) and ten infants ranging in age from one to ten months (I group). They underwent abdominal surgery under general anaesthesia with halothane and nitrous oxide in oxygen. The O2- production (speed and amount) was measured perioperatively using the cytochrome c reduction method. Both groups showed a decrease in the speed and amount of O2- production during and after surgery. The decrease in O2- production reached its lowest level three hours postoperatively or at the end of surgery in both groups. The O2- production in the I group returned to the basal value 48 hr postoperatively. In contrast, the O2- production in the N group was still lower 48 hr after surgery than before anaesthesia. Although the total amount of O2- production by neutrophils in one mL of peripheral blood remained unchanged in the I group, the total amount of O2- production in the N group decreased at the end of surgery and thereafter. These data indicate that even relatively minor abdominal surgery with halothane anaesthesia may be associated with perioperative neutrophil impairment in both neonates and infants. This impairment of neutrophil function in infants but not in neonates may be compensated by an increase in neutrophil numbers. It is possible that perioperative susceptibility of neonates to bacterial infections is attributable, at least in part, to the inhibition of O2- production in neutrophils by surgery and general anaesthesia.

Abdomen↗
PubMed1993

Effects of surfactant on lung injury induced by hyperoxia and mechanical ventilation in rabbits.

We evaluated the effects of exogenous surfactant on lung injury caused by 100% oxygen and mechanical ventilation in rabbits. Surfactant-treated rabbits (n = 9) were ventilated with 100% oxygen for 36 hours and bovine surfactant was given via the trachea 12 hours after the start of mechanical ventilation. Saline-treated (n = 9) rabbits were treated identically, except that they received saline without surfactant. There were no significant changes in hemodynamics, lung mechanics, or arterial oxygen tension during artificial ventilation. Albumin concentration in the bronchoalveolar lavage fluid (BALF) of saline-treated rabbits was slightly higher than those in surfactant-treated rabbits and significantly higher than in non-treated rabbits. C3a concentration in BALF was significantly higher in saline-treated rabbits than in surfactant-treated and non-treated rabbits. In addition, the wet-to-dry lung weight ratio was significantly lower in surfactant-treated rabbits than in saline-treated rabbits (5.06 +/- 0.10 vs. 5.67 +/- 0.14, P < 0.05). Light microscopy revealed hyaline membrane formation in saline-treated rabbits, but fewer changes were observed in surfactant-treated rabbits. Electron microscopy revealed extensive endothelial cell destruction in saline-treated rabbits, while such changes except endothelial cell swelling were not observed in surfactant-treated rabbits. We conclude that exogenous surfactant attenuated lung injury caused by oxygen exposure and ventilation.

Journal Article↗
PubMed1993

Purification and some properties of proteinase from Pseudomonas fluorescens No. 33.

The extracellular proteinase from Pseudomonas fluorescens No. 33 was purified to electrophoretic homogeneity by a procedure including precipitation with HCl and (NH4)2SO4, and column chromatography. The enzyme was purified 170-fold giving a yield of 7% of the original activity. The molecular mass of the purified enzyme was 48,000 by SDS-PAGE. The optimum pH and temperature for the hydrolysis of casein were 8.0-9.8 and 30-35 degrees C respectively. The enzyme was more thermostable in synthetic milk salts solution than in 0.1 M-sodium phosphate buffer, but was heat-labile at 50 degrees C in both buffer systems. The activity was inhibited by o-phenanthroline, Hg2+, Cu2+, Fe2+ and, to a lesser extent, Ni2+. Caseins were susceptible to the proteinase, but degradation patterns were dependent on the form of the casein.

Caseins↗
PubMed1993

Efficacy of oral clonidine premedication in children.

BACKGROUND: Clonidine, an alpha 2-adrenoceptor agonist, has been shown to be effective as a preanesthetic medication in adults. The current study was designed to investigate the efficacy of two doses of oral clonidine as a premedicant preceding oral atropine in children. METHODS: In a prospective, randomized, double-blind, controlled clinical trial, 105 children, aged 4-12 yr, undergoing elective ophthalmologic surgery received 0.4 mg/kg diazepam, 2 micrograms/kg clonidine, or 4 micrograms/kg clonidine orally. These agents mixed with apple juice were administered 105 min before the estimated time of induction of anesthesia, and were followed by treatment with 0.03 mg/kg oral atropine 60 min before anesthesia. A blinded observer noted the children's level of sedation, quality of separation from parents, and degree of acceptance of mask application during inhalation of nitrous oxide used for establishment of venous access. Anesthesia was induced with 5 mg/kg thiamylal, and tracheal intubation was facilitated with 0.2 mg/kg vecuronium. Hemodynamic changes after tracheal intubation were compared among the three groups. RESULTS: Clonidine produced significant sedation, and the effect was dose related. Clonidine, 4 micrograms/kg, provided better quality of separation and acceptance of mask than the two other regimens. This dose of clonidine attenuated the increases in blood pressure and heart rate after tracheal intubation. No clinically significant perioperative hypotension or bradycardia was observed. CONCLUSIONS: These data indicate that, even in pediatric surgery, the combination of 4 micrograms/kg and 0.03 mg/kg oral clonidine is an effective premedication. However, the safety and optimal dose of clonidine in this setting remain to be determined.

Administration, Oral↗