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Biomedical subjects

K Hashiba

Publications and source records attributed to K Hashiba.

At least 37 records · Page 2Linked to original sources

[General pharmacology of T-3761, a new oral quinolone antibacterial agent (2). Effect on the respiratory and cardiovascular systems, autonomic nervous system and other functions].

General pharmacological effects of T-3761, a new oral quinolone antibacterial agent, on the respiratory and cardiovascular systems, autonomic nervous system and other functions were investigated in laboratory animals. The results obtained are summarized as follows. 1. Respiratory and cardiovascular systems: Oral administration of T-3761 at doses of 100-1,000 mg/kg did not affect in conscious rats. But intravenous administration of T-3761 at doses of 10-100 mg/kg caused an increase in respiratory rate, induced hypotension, caused increase or decrease in heart rate and altered ECG patterns (elevation of T waves and reduction of voltage of QRS complexes, etc.) in anesthetized dogs. Intravenous administration of T-3761 at doses of 10-100 mg/kg showed respiratory rate increase or decrease, hypertension, heart rate decrease and ECG patterns changes (T waves elevation and extrasystole) in anesthetized rabbits. 2. Autonomic nervous system and smooth muscle organs: T-3761 increased the epinephrine-induced contraction of the isolated guinea pig vas deferens at concentration of 10(-5)-10(-4) g/ml. T-3761 decreased the acetylcholine-induced contraction of the isolated guinea pig ileum and epinephrine-induced relaxation of the isolated guinea pig trachea-chain at concentration of 10(-4) g/ml. T-3761 increased the norepinephrine-induced contraction of the isolated rabbit thoracic aorta at concentration of 10(-4) g/ml. Oral administration of T-3761 at a dose of 1,000 mg/kg exerted slight mydriasis in mice. 3. Digestive system: T-3761 decreased the spontaneous motilities of isolated ileum and colon at concentration of 10(-4) g/ml. Oral administration of T-3761 at a dose of 1,000 mg/kg inhibited gastric output and intestinal transit time in rats or mice. 4. Renal functions: Oral administration of T-3761 at a dose of 300 mg/kg increased Na+ excretion but did not affect PSP excretion in rats. 5. Hematological examinations: T-3761 showed no effects on resistance to hemolysis, blood coagulation and platelet aggregation in rabbits at concentration of 10(-6)-10(-4) g/ml. Oral administration of T-3761 at dose of 100-1,000 mg/kg did not affect bleeding time or blood glucose level in rats. 6. Miscellaneous effects: Intravenous administration of T-3761 at a dose of 100 mg/kg slightly inhibited the twitch tension of gastrocnemius in anesthetized rats. Oral administration of T-3761 at doses of 300-1,000 mg/kg exerted slight augmentation of carrageenin-induced hind paw edema in rats. From these results, it can be assumed that T-3761 had a wide safety margin as an oral antibacterial agent.

Animals↗

Laparoscopic transhiatal esophagectomy with esophagogastroplasty.

Twelve patients with benign and malignant esophageal diseases were treated by transhiatal esophagectomy, without thoracotomy, using abdominal-mediastinal dissection conducted by videolaparoscopy. A cervical approach was used to retrieve the esophagus and to perform the esophagogastric anastomosis. The procedure was indicated in patients with advanced achalasia of the esophagus, severe reflux stenosis, squamous cell carcinoma, and adenocarcinoma of the esophagus. Three pleural perforations occurred during surgery. Blood loss was minimal. One patient required conversion to open surgery, two patients were submitted to chest drainage, and three had transitory dysphonia. One patient had an anastomotic leak with subsequent stenosis requiring endoscopic dilatation. No mortality occurred in this small series.

Adenocarcinoma↗

Laparoscopic management of choledocholithiasis.

The authors report on a group of 114 patients with common bile duct (CBD) stones who were treated by laparoscopic surgery. Management through the cystic duct was considered the first option. Choledochotomy was used for those patients in which the cystic approach was not possible or was unsuccessful. Transcystic lithotripsy was considered for patients with CBD stones in disproportion with the size of the cystic duct. Laparoscopic antegrade sphincterotomy was indicated as a drainage procedure. The transcystic approach was used in 89.5% of the patients; choledochotomy was used in 6.2%; and both ways were used in 4.3%. Different procedures were used, including mechanical and electrohydraulic lithotripsy, choledochotomy with T-tube or endoprostheses drainage, laparoscopic sphincterotomy, end-to-end common bile duct anastomosis, and choledochoduodenum anastomosis. One of the patients was in the 21st week of pregnancy. The laparoscopic approach to choledocholithiasis was successfully performed in 94.8% of the patients. Mean hospital stay was 1.7 days. There was a 6.2% incidence of complications and the mortality rate was 0.9%. In 84.3% of the patients, the transcystic approach was used successfully, with a complication rate of 4.9% and a mean hospital stay of 1.6 days. Three patients were converted to open surgery early in this series. Thus far, one patients has presented residual CBD stones. The results obtained suggest that laparoscopic common bile duct exploration is a technically feasible procedure, with low complication and mortality rates, although it requires adequate selection of patients and a variety of techniques and types of equipment.

Common Bile Duct↗

Mechanism of the suppression of repetitive atrial firing by isoproterenol--comparison with disopyramide.

To investigate whether isoproterenol (Iso) could suppress the initiation of repetitive atrial firing (RAF), we investigated its effect on RAF in comparison with that of disopyramide (Diso). Extrastimuli at a basic cycle length of 500 ms were delivered from the high right atrium in 49 patients who received an intravenous infusion of Iso (0.01 microgram/kg per min) and in 39 patients given intravenous Diso (2 mg/kg per 10 min). Induction of RAF, the atrial effective refractory period (A-ERP), and the maximum conduction delay (MCD) were measured. Iso abolished the induction of RAF in 13/19 (68%) patients, while Diso did so in 13/22 (59%) patients. Thirty-four of the 41 patients with RAF in the baseline study had an A-ERP < 250 ms and an MCD > 40 ms. Iso significantly decreased the A-ERP from 205 +/- 26 to 194 +/- 23 ms (P < 0.01) and significantly decreased the MCD from 67 +/- 24 to 39 +/- 16 ms (P < 0.0001) in 19 patients with RAF. On the other hand, Diso significantly increased the A-ERP from 203 +/- 31 to 235 +/- 36 ms (P < 0.0001), and significantly diminished the MCD from 68 +/- 31 to 55 +/- 30 ms (P < 0.01) in 22 patients with RAF. In patients with new RAF (n = 7) or re-induced RAF (n = 14) during Iso or after Diso, the MCD was more than 40 ms. Our results suggest that there are two different modes of RAF suppression, i.e. shortening or lengthening of the A-ERP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Depressor effect of intraventricular administration of calcium on spontaneously hypertensive rats.

The role of central Ca2+ in the regulation of blood pressure (BP) was investigated in conscious spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY). Ten microliters of a high Ca2+ solution (Ca2+: 32.6 mM) administered intracerebroventricularly (i.c.v.) decreased the mean arterial pressure (MAP) for more than 20 min in SHR (n = 7, P < 0.005), while no change of MAP was observed in the WKY (n = 6). This depressor response to Ca2+ i.c.v. was dose-dependent at Ca2+ concentrations between 16.3 and 65.2 mM. We also investigated the effect of high Ca2+ i.c.v. in SHR after pretreatment with Ca2+ channel blockers, diltiazem (60 micrograms/10 microliters) or nisoldipine (4, 8, 16 and 32 micrograms/10 microliters), administered i.c.v., the autonomic ganglion blocker, hexamethonium (50 mg/kg), administered i.v. and alpha-methyl-p-tyrosine (100 and 400 micrograms/10 microliters) delivered i.c.v. Pretreatment with i.c.v. diltiazem (n = 8) or nisoldipine (n = 5 for 8 micrograms, n = 6 for 4, 16, 32 micrograms) abolished and/or blunted the decrease of MAP due to high Ca2+. Hexamethonium administered i.v. (n = 6) also canceled the depressor action of i.c.v. Ca2+. Pretreatment with 100 micrograms of i.c.v. alpha-methyl-p-tyrosine could not prevent the depressor action of i.c.v. Ca2+; however, 400 micrograms of alpha-methyl-p-tyrosine administered i.c.v. abolished the effect of i.c.v. Ca2+. Furthermore Ca2+ channel blockers administered i.c.v. in themselves increased MAP in SHR (P < 0.05). These results suggest that central Ca2+ is involved in the central regulation of BP in SHR. This effect may be mediated through changes in sympathetic activity.

Animals↗

Impaired left ventricular filling in borderline hypertensive patients without cardiac structural changes.

To determine the effect of borderline hypertension on left ventricular diastolic performance, 16 patients with borderline hypertension who did not have left ventricular hypertrophy and 16 age-sex-matched patients with normotension of similar age and body mass index were investigated. Pulsed Doppler echocardiography was used to record left ventricular filling signals at rest and immediately after supine ergometer exercise. All subjects had normal left ventricular structure and systolic function. At rest the borderline hypertension group in comparison with the normotension group had a depressed peak velocity of early filling (E) (44 +/- 7 vs 54 +/- 10 cm/sec; p < 0.01), no enhanced peak velocity of late filling (A) (52 +/- 8 vs 50 +/- 11 cm/sec; not significant), and a reduced E/A ratio (0.9 +/- 0.2 vs 1.1 +/- 0.3; p < 0.05). Atrial filling time and preejection period were similar in the two groups. The effect of exercise on left ventricular filling velocity in patients with borderline hypertensive resembled that in those with normotension. Percentage changes in E (+14% +/- 12% vs +14% +/- 13%) and A (+13% +/- 8% vs 11% +/- 12%) were equivalent, suggesting a preserved diastolic reserve for exercise in the borderline hypertension group. In conclusion, borderline hypertension appears to be predictive of early filling impairment, and a late filling compensative mechanism is not yet apparent. These findings in borderline hypertension without apparent cardiac damage call for clinical attention to prevent further deterioration in cardiac function.

Adult↗

Augmented central pressor action of magnesium in SHR.

This study attempted to determine whether central magnesium (Mg) influences the regulation of blood pressure (BP). An intracerebroventricular (icv) injection of a high Mg2+ solution (190.0 mEq/L, 10 microL), made by adding MgC12 to artificial cerebrospinal fluid, increased the mean BP in both conscious spontaneously hypertensive rats (SHR; n = 17, p < 0.001) and Wistar Kyoto rats (WKY; n = 8, p < 0.005). Spontaneously hypertensive rats showed a greater pressor response than WKY (+11.7 +/- 0.9 mm Hg versus +3.5 +/- 1.1 mm Hg, p < 0.001). This pressor response to Mg2+ given icv was dose-dependent in the range of Mg2+ concentration between 47.5 and 190.0 mEq/L in SHR. A high Mg2+ solution (190.0 mEq/L), made by adding MgSO4 given icv, also increased the mean BP in SHR (n = 7, p < 0.001) and WKY (n = 6, p < 0.01), whereas the high osmolarity solution (340 mOsm/kg H2O) given icv did not change the mean BP in either SHR or WKY. Also administered was a high Mg2+ solution icv after either hexamethonium bromide (Hx; 50 mg/kg intravenously) or arginine vasopressin antagonist (aAVP, (CH2)5Tyr(Me)AVP, 30 micrograms/kg i.v.). The pressor response to the high Mg2+ solution was abolished by arginine vasopressin antagonist both in SHR and WKY, although it was not canceled by Hx. A high Mg2+ solution administered icv caused a 3.5-fold increase in plasma arginine vasopressin concentration in SHR (n = 5, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Electrophysiologic effects of a new class III antiarrhythmic agent, E-4031, on atrial flutter, atrial refractoriness, and conduction delay in a canine sterile pericarditis model.

Numerous studies have shown that E-4031 generally prolongs the atrial effective refractory period (AERP) without affecting cardiac conduction. The effects of E-4031 on AERP and cardiac conduction at short cycle lengths (CLs) close to the AERP were measured in 12 dogs with sterile pericarditis. Three pairs of electrodes were sutured at three sites in the atria 4 days after the model was created. We measured AERP and maximum conduction delay (MCD) after 8 beats train at CLs of 400, 300, 200 and 150 ms before and during continuous infusion of E-4031 (0.1 microgram/kg/min) that followed an initial dose of 10 micrograms/kg/min/5 min. E-4031 interrupted sustained atrial flutter (AF) (> or = 10 min) in 4 of 5 episodes and atrial fibrillation (> or = 10 min) in 4 of 4. The CL of AF defined as a rapid atrial rhythm (rate > or = 240 beats/min) in five episodes studied in the sterile pericarditis model was significantly (p < 0.005) prolonged from 120 +/- 8 to 160 +/- 17 ms. There were significant (p < 0.005) increases in AERP at each CL, and prolongation of AERP was 39 +/- 18, 31 +/- 14, 23 +/- 14, and 16 +/- 14 ms at CL 400, 300, 200, and 150 ms, respectively. E-4031 produced less prolongation of AERP at short pacing CLs and had no effect on conduction time during atrial rapid pacing at CLs > 150 ms. E-4031 did not prolong MCD at CL 400 ms, but did prolong MCD at CLs of 300, 200, and 150 ms, despite prolongation of AERP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluation of myocardial damage in Duchenne's muscular dystrophy with thallium-201 myocardial SPECT.

Myocardial damage and cardiopulmonary functions in patients with Duchenne's muscular dystrophy (DMD) were assessed using thallium-201 myocardial single-photon emission computed tomography (SPECT) and technetium-99m multigated radionuclide angiography. Twenty-five patients with DMD were divided into 4 groups according to percent of perfusion defect (%PD) calculated by the bull's-eye method and age. PD was detected in 24 (96.0%) of 25 patients with DMD, and it spread from the left ventricular lateral wall to the anterior wall and/or interventricular septum. PD was detected even in a 6-year-old DMD boy. Patients in Group I (%PD > or = 10 and age < 15 years old) were shown to have a higher risk of left-sided heart failure without respiratory failure. Patients in Group II (%PD > or = 10 and age > or = 15) showed decreased pulmonary function and worsened arterial blood gas values as compared with Group IV (%PD < 10 and age > or = 15). There was no significant difference in cardiac function among the 4 groups. It is postulated that myocardial damage in Group II patients is dependent primarily on a deficiency of dystrophin and on chronic respiratory failure, and that some of them are at risk of cardiopulmonary failure. It is concluded that myocardial SPECT is useful for the early diagnosis of myocardial damage and evaluation of cardiopulmonary function in DMD patients.

Child↗

Laparoscopic antegrade sphincterotomy.

The technique of laparoscopic antegrade sphincterotomy is described. This procedure was used to clear the common bile duct in 22 selected patients with documented choledocholithiasis. Indications for attempting laparoscopic antegrade sphincterotomy included multiple common bile duct stones, one or more common hepatic or intrahepatic stones, a dilated common bile duct requiring a drainage procedure, and suspicion of papillary stenosis. No major complications or mortality was observed. Mild hyperamylasemia was observed in two patients. However, both were asymptomatic, and serum amylase levels rapidly returned to normal. One patient was noted to have a drop in her hematocrit from a preoperative value of 39% to a postoperative value of 33%. Laparoscopic antegrade sphincterotomy added a mean of 17 min to the operative procedure. The mean postoperative stay was 1.4 days. The results of this study suggest that laparoscopic antegrade sphincterotomy may prove to be a useful modality in selected patients with complicated choledocholithiasis.

Adult↗

Contribution of the central interaction between calcium and sodium to hemodynamic regulation in spontaneously hypertensive rats.

The contribution of the central interaction between calcium and sodium to hemodynamic regulation was assessed in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. The effect of a high calcium solution (Ca2+, 130 mg/dl, 10 microliters) infused into the cerebral ventricle (i.c.v.) on hemodynamic responses induced by a high sodium solution (Na+, 1,000 mEq/1, 10 microliters) i.c.v. and the mechanism by which high Ca2+ affects the hemodynamic responses induced by high Na+ i.c.v. were studied. High Na+ i.c.v. induced a pressor response with tachycardia in the SHRs, but induced a pressor response with reflex bradycardia in the WKYs. Prior treatment with high Ca2+ i.c.v. attenuated the pressor response induced by high Na+ i.c.v. (+55.6 +/- 4.4 to +33.1 +/- 3.2 mmHg, P < 0.01) and restored reflex bradycardia (+86.4 +/- 7.7 to -26.7 +/- 7.6 bpm, P < 0.01) in SHRs. Whereas prior treatment with high Ca2+ i.c.v. attenuated the pressor response (+35.7 +/- 2.0 to +22.2 +/- 4.0 mmHg, P < 0.05), it did not alter the degree of reflex bradycardia (-81.7 +/- 7.1 to -69.2 +/- 120 bpm, n.s.) in WKYs. Ganglionic blockade attenuated the pressor response (+56.9 +/- 3.5 to +42.9 +/- 2.3 mmHg, P < 0.05) and restored reflex bradycardia (+82.1 +/- 10.3 to -65.9 +/- 11.0 bpm, P < 0.01) in SHRs, whereas, inhibition of arginine vasopressin attenuated the pressor response without modification of the tachycardic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Coronary artery-cardiac chamber shunt: cineangiographic analysis.

Coronary artery-cardiac chamber shunts (CA-CC shunts) were observed in 101 out of 2267 consecutive patients (4.5%) receiving selective coronary angiography. In these patients, contrast medium injected into the coronary artery escaped directly into the cardiac chamber. CA-CC shunts were angiographically classified into the following two types. Type I: The endocardial layer was diffusely opacified, and contrast medium escaped into the cardiac chamber on systole (n = 83). Type II: Contrast medium escaped directly into the cardiac chamber via an undilated branch (n = 11). Type I and type II shunts were observed simultaneously in 7 patients. It is speculated that type I is a shunt via a persistent arterio-sinusoidal vessel, while type II is a shunt via a persistent arterio-luminal vessel. Both types were observed frequently (24.9%) in hypertrophic cardiomyopathy. The degree of CA-CC shunts in hypertrophic cardiomyopathy was not influenced by the presence or absence of myocardial squeezing. CA-CC shunts are considered to be due to an abnormality in the coronary microcirculation of the myocardium. We describe the angiographic features of the two types of CA-CC shunt and discuss their pathophysiological significance.

Adolescent↗

Electrophysiological abnormalities of the atrial muscle in patients with sinus node dysfunction without tachyarrhythmias.

The duration and the number of fragmented deflections of the right atrial electrograms were assessed and quantitatively measured in 74 patients who underwent endocardial catheter mapping during sinus rhythm. The bipolar electrograms were recorded at 12 sites in the right atrium. An abnormal atrial electrogram was defined as a duration of 100 ms or longer, and/or 8 or more fragmented deflections, according to our previous criteria. The patients were divided into two groups. The control group consisted of 41 age-matched patients with normal sinus node function and without paroxysmal atrial fibrillation. The study group comprised 33 patients with sinus node dysfunction but without tachyarrhythmias. Abnormal atrial electrograms were observed in 8 (19.5%) control patients, and in 16 (48.5%) sinus node dysfunction patients; p < 0.02. The total number of abnormal electrograms was 14 (2.89%) of 483 atrial electrograms in controls, and 36 (9.38%) of 384 in the study group; p < 0.0002. The mean duration (75.6 +/- 17) and the mean number of fragmented deflections (4.1 +/- 2) of the total atrial electrograms in the sinus node dysfunction group was significantly greater than that in controls (70.9 +/- 11 and 3.6 +/- 1, respectively); p < 0.01. The mean number of abnormal electrograms per patient in the study group (1.06 +/- 1.8) was significantly higher than that in the control group (0.3 +/- 0.8); p < 0.05. These data suggest that: (1) there is a significantly greater electrophysiological abnormality of the atrial muscle in patients with sinus node dysfunction but without paroxysmal atrial fibrillation than in age-matched controls, and (2) not only the sinus node but also the atrial muscle is electrophysiologically altered in patients with sinus node dysfunction but without tachyarrhythmias.

Adult↗

Electrophysiological abnormalities of the atrial muscle in patients with manifest Wolff-Parkinson-White syndrome associated with paroxysmal atrial fibrillation.

We investigated the electrophysiological properties of the atrial muscle in 33 patients with manifest Wolff-Parkinson-White syndrome. Group I consisted of 13 patients with paroxysmal atrial fibrillation and group II consisted of 20 patients without paroxysmal atrial fibrillation. The anterograde and retrograde effective refractory periods of the accessory pathway and the inducibility of atrioventricular reciprocating tachycardia were not significantly different between the two groups. Endocardial electrograms, obtained by right atrial catheter mapping, were recorded during sinus rhythm from 12 sites of the right atrium in 12 of the 13 group I patients and in all group II patients. An abnormal atrial electrogram was defined as 100 msec or longer in duration, and/or the occurrence of eight or more deflections. Ten (83%) of the 12 group I patients had abnormal atrial electrograms, while only two (10%) of the 20 group II patients had abnormal atrial electrograms, and the difference was significant (P less than 0.01). Thirty-six (26%) of the total 139 electrograms obtained from 12 group I patients and two (1%) of the total 199 electrograms obtained from 20 group II patients fulfilled the criteria for an abnormal atrial electrogram, and the difference was significant (P less than 0.01). The fragmented atrial activity zone, interatrial conduction delay zone, and repetitive atrial firing zone obtained by right atrial extrastimulation were significantly wider in group I than in group II, respectively. It was concluded that electrical abnormalities of the atrial muscle may play an important role in the occurrence of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome.

Adult↗

Different distribution of abnormal endocardial electrograms within the right atrium in patients with sick sinus syndrome.

BACKGROUND: Prolonged and fractionated right atrial endocardial electrograms are characteristic of paroxysmal atrial fibrillation (idiopathic or associated with sick sinus syndrome). The distribution of these abnormal atrial electrograms within the right atrium and the way it is related to the likelihood that patients with sick sinus syndrome will develop paroxysmal atrial fibrillation was studied. METHODS: Endocardial catheter mapping of the right atrium during sinus rhythm was performed in 41 control patients with normal sinus node function and without paroxysmal atrial fibrillation, in 33 patients with sick sinus syndrome but without tachycardia, and in 27 patients with sick sinus syndrome and paroxysmal atrial fibrillation (group 3). The bipolar electrograms were recorded at 12 sites in the right atrium and an abnormal atrial electrogram was defined as lasting > or = 100 ms and/or showing eight or more fragmented deflections. RESULTS: 1195 atrial endocardial electrograms were assessed and quantitatively measured. In patients with sick sinus syndrome and paroxysmal atrial fibrillation 54% of the abnormal atrial electrograms were recorded from the high right atrium, 28% from the mild right atrium, and 18% from the low right atrium. However, in patients with sick sinus syndrome without tachycardia 78% of the abnormal atrial electrograms were recorded from the high right atrium and 22% from the mid right atrium. No abnormal electrograms were recorded from the low right atrium. CONCLUSIONS: In patients with sick sinus syndrome without tachycardia abnormal atrial electrograms generally came from the high right atrium but in patients with sick sinus syndrome and paroxysmal atrial fibrillation abnormal atrial electrograms were more widely distributed in the right atrium. In patients with sick sinus syndrome the greater the extent of the compromised atrial muscle, the greater the likelihood that paroxysmal atrial fibrillation will develop.

Adult↗