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Biomedical subjects

S Morooka

Publications and source records attributed to S Morooka.

At least 109 records · Page 6Linked to original sources

Effect of the selective PAF antagonist SM-10661 on an asthmatic model. 1. Effect on passive anaphylactic bronchoconstriction in guinea pigs.

The effect of SM-10661, a selective antagonist of platelet-activating factor (PAF), on passive anaphylactic bronchoconstriction was examined in guinea pigs. A challenge of ovalbumin to passively sensitized guinea pigs induced bronchoconstriction, which peaked at 4 min. When SM-10661 was administered intravenously 2 min before ovalbumin challenge, bronchoconstriction was inhibited dose-dependently with an ID50 of 68 mg/kg. In guinea pigs pretreated with 15 micrograms/kg mepyramine which is a suboptimal dose, antigen-induced bronchoconstriction peaked at 4-6 min, but was inhibited by SM-10661 with an ID50 of 21 mg/kg. When guinea pigs were pretreated intravenously with 2.5 mg/kg mepyramine, 1 mg/kg indomethacin and 0.01 mg/kg propranolol, the antigen-induced bronchoconstriction peaked at 6 min. SM-10661 inhibited the response with an ID50 of 45 mg/kg. Histamine- and leukotriene D4-induced bronchoconstrictions were unaffected by up to 100 mg/kg SM-10661. Ovalbumin challenge of minced lungs from passively sensitized guinea pigs triggered the release of leukotrienes and histamine. SM-10661 had no effect on the antigen-induced release of peptide leukotrienes or histamine up to 10(-4) M. These results indicate that SM-10661 may be a useful tool to investigate the role of PAF in antigen-induced anaphylactic bronchoconstriction.

Anaphylaxis↗

Effect of the selective PAF antagonist SM-10661 on an asthmatic model. 2. Effect on antigen-induced dual asthmatic response and infiltration of leukocytes into airways in actively sensitized conscious guinea pigs.

The effect of a selective platelet-activating factor (PAF) receptor antagonist, SM-10661, on antigen-induced dual asthmatic response and leukocyte infiltration into the airways of actively sensitized conscious guinea pigs was investigated. The animals were pretreated with mepyramine maleate (10 mg/kg i.p.) and then challenged with ovalbumin. The inhalation of ovalbumin caused an immediate decline in specific airway conductance (sGaw) which peaked at 5 min after the challenge. sGaw gradually returned to the baseline 6 hr after the challenge. After the early asthmatic response (EAR), a second phase change, a late asthmatic response (LAR) in sGaw peaking at 17-20 hr was observed. When 1% w/v disodium cromoglycate was inhaled for 2 min on two occasions, EAR was not affected, but LAR was significantly inhibited. Oral administration of 50 mg/kg fenoterol (30 min before challenge) significantly inhibited EAR, but had no significant effect on LAR. SM-10661 administered orally 1 hr before the challenge inhibited EAR dose-dependently (50% inhibitory dose (ID50); 59 mg/kg, but was even more effective against the LAR (ID50); 13-16 mg/kg). When 30 mg/kg of SM-10661 was administered orally 6 hr after ovalbumin challenge, LAR was completely inhibited. The number of total cells, macrophages and eosinophils in bronchoalveolar lavage fluids rose significantly 17 hr after antigen challenge compared to that observed after saline challenge. The number of neutrophils and lymphocytes also increased in response to the ovalbumin challenge, but not significantly. SM-10661 (30 mg/kg) administered orally 1 hr before the challenge significantly inhibited the increase in total cells, macrophages and eosinophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of a selective PAF antagonist SM-10661 ((+/-)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl) on experimental disseminated intravascular coagulation (DIC).

Intravenous infusion of endotoxin (0.25 mg/kg/hr for 4 hr) was shown to induce disseminated intravascular coagulation (DIC) in rats, which resulted in hypofibrinogenemia, prolongation of prothrombin (PT) and partial thromboplastin time (PTT), thrombocytopenia, and elevated levels of fibrinogen/fibrin degradation products (FDP). Oral administration (100 mg/kg) of the selective PAF antagonist, SM-10661 ((+/-)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl), counteracted the changes caused by the endotoxin. Intravenous infusion of SM-10661 (6mg/kg bolus 2 min before endotoxin infusion + 6 mg/kg/hr for 4 hr infusion) also counteracted DIC. When suboptimal doses of gabexate mesilate, a synthetic protease inhibitor (3 mg/kg i.p.), and SM-10661 (2 mg/kg bolus + 2 mg/kg/hr for 4 hr infusion) were administered concomitantly, hematological parameters improved. The results suggest that PAF may play a role in the pathogenesis of DIC, and that together with the results already reported for other PAF antagonists, SM-10661 may be useful in the treatment of DIC.

Administration, Oral↗

Lower pacemaker in high degree atrioventricular block is modulated electrotonically by atrial excitations.

To see if the lower pacemaker in patients with atrioventricular (AV) block was modulated electrotonically by atrial excitation, we studied R-R intervals in two groups of AV block patients using a phase response curve (PRC). Group I consisted of 20 patients with high degree AV block, including seven patients in whom complete AV block was transiently observed in the course of acute inferior myocardial infarction. Group II consisted of 19 patients with complete AV block. In every patient, PRC was obtained from the continuous electrocardiogram by plotting each R1-R2 interval (response) on the ordinate as a function of the R1-Px interval (phase, x = 1, 2 ...) on the abscissa. In Group I, the R-R interval was prolonged when the P wave fell in the initial half of the R-R interval, and was abbreviated when the P wave fell in the later half of the cycle. In Group II, the fluctuation of the R-R interval was minimum. In ten group I patients, with the improvement of the AV block, PRC became sharper and transition from prolongation to shortening occurred at shorter R-P intervals. We conclude that, in Group I, lower pacemaker was modulated electrotonically by atrial excitations through decreased electrical coupling along the AV node.

Aged↗

Nitroglycerin-induced transient coronary artery occlusion.

Nitroglycerin induced a paradoxical disappearance of a stenosed coronary artery in a 57-year-old man with non-Q wave myocardial infarction. On the coronary angiogram, the left anterior descending coronary artery (with a 95% stenosis) became completely invisible 2 min after 0.3 mg sublingual nitroglycerin. Three minutes later, the artery was opacified again. This transient occlusion may have resulted from a passive collapse of the distal portion of the artery, due to insufficient access of nitroglycerin across the stenotic region.

Animals↗

Aortic dissection associated with aortitis syndrome.

A 50-year-old woman with aortitis syndrome complicated by aortic dissection, is reported. The dissection was observed at the level of the descending thoracic aorta by aortography and at the intimal side of the dilated aorta on CT. An aneurysm of the right subclavian artery and a diffusely thick wall of the abdominal aorta were also observed. This case suggests that the uneven wall of the aorta in aortitis syndrome might be dissected at the intimal side by dilatation.

Aneurysm↗

Global and regional abnormalities of left ventricular diastolic filling in hypertrophic cardiomyopathy.

Left ventricular diastolic filling was studied by left ventriculography in 17 patients with hypertrophic cardiomyopathy (HCM). In 8 patients this manifested as a spadelike shape (HCM-S type) on the left ventriculogram, and in 9 patients as a banana shape (HCM-B type). Seven patients were studied as controls. Left ventricular end-diastolic pressure was higher in HCM than in controls. In HCM, peak filling rate was decreased from 1.57 +/- 0.28 of the control to 1.28 +/- 0.20 (p less than 0.05), and the time to peak filling rate was prolonged from 27 +/- 6%DT of the control to 37 +/- 7%DT (p less than 0.01). Serial volume analysis in diastole showed filling fraction was also significantly decreased to 8.2 +/- 4.1 (p less than 0.001) at the 25% diastole time and 29.6 +/- 7.2 (p less than 0.01) at half time, compared with 19.8 +/- 6.3 and 32.8 +/- 5.8 for controls, respectively. In HCM-S type, the rate of distention of left ventricular radial axes at the apical area was lower at early and mid-diastole. In HCM-B type, the rate at the basal area was lower at early and mid-diastole. Results suggest that the left ventricular diastolic filling in HCM was impaired not uniformly but regionally in the hypertrophic area at early and mid-diastole.

Adult↗

[Hypertrophic cardiomyopathy associated with anomalous origin of the left coronary artery from the right sinus of valsalva].

A 47 year old Japanese male with exertional shortness of breath, cardiac murmur and ECG abnormalities was examined with invasive and non-invasive cardiology techniques that disclosed hypertrophic cardiomyopathy, and the anomalous origin of the left coronary artery from the right sinus of Valsalva. Although both situations have been known to cause sudden death especially under a state of strenuous physical stress, his exercise thallium scintigraphy performed with the symptom limited maximal test did not uncover any significant myocardial ischemia or exercise induced malignant arrhythmias. This is a very rare association of two distinctly identified clinical situations highly indicative of a likelihood of sudden cardiac death. Therefore, careful observation is needed.

Cardiac Catheterization↗

Carbamazepine-induced bradycardia-tachycardia syndrome with pharmacological analysis and concurrent ECG monitoring.

The authors present a patient with carbamazepine-induced bradycardia-tachycardia syndrome, a rare type of drug-induced sinus node dysfunction. In this case, they established a clear-cut relationship between plasma carbamazepine concentration and the frequency of sinus arrests, following episodes of supraventricular tachycardia. As the pharmacological analysis of drug-induced sinus node dysfunction by concurrent ECG monitoring is very limited, the findings give an insight into the mechanism of this disorder.

Aged↗

Chronic encapsulated intracerebral hematoma associated with cavernous angioma: a case report.

The case of a patient with a chronic encapsulated intracerebral hematoma associated with a cavernous angioma is reported. In spite of a huge space-occupying lesion in the frontal lobe, our patient showed no focal neurological deficit. The clinical picture suggested a slowly growing brain tumor. Intraoperative findings revealed a liquefied intracerebral hematoma with a thick capsule. Pathological investigations demonstrated a capsule rich in neovascularity with a cavernous angioma attached to it. It is presumed that initial bleeding from the cavernous angioma encouraged capsule formation similar to the membrane of chronic subdural hematomas and that repeated bleeding from the capillaries of the capsule allowed the expansion of the hematoma.

Adolescent↗

Right-to-left shunting through a patent foramen ovale caused by pulmonary hypertension associated with rheumatoid arthritis and Sjögren's syndrome: a case report.

This case report presents a fifty-four-year-old woman with right-to-left shunt in the atrium. It seemed clinically at first that the shunt was due to atrial septal defect. However, she also had pulmonary disease associated with rheumatoid arthritis and Sjögren's syndrome. At autopsy atrial septal defect was not evident, but a patent foramen ovale and pulmonary artery disease were observed. This case suggests that pulmonary hypertension secondary to rheumatoid arthritis and Sjögren's syndrome could lead to right-to-left shunting through a patent foramen ovale.

Arthritis, Rheumatoid↗

Headache angina with fatal outcome.

We report 2 fatal cases of angina pectoris in patients who complained primarily of headache during the ischemic attack. The first patient, who was hospitalized because of headache and chest pain, demonstrated repeated ST-segment elevation and fatal ventricular fibrillation on ambulatory ECG monitoring. The second patient had post-infarction angina preceded by headache and by ST-segment elevation in the precordial leads. She eventually died of reinfarction. The mechanism of the headache in relation to the angina pectoris is discussed.

Aged↗

Coronary artery disease associated with aortitis syndrome in older patients.

Coronary artery disease associated with aortitis syndrome was studied in relation to the coronary artery lesions and age. Four (21%) of 19 patients with aortitis syndrome had coronary artery disease and the mean age of the 4 patients was 53 +/- 14 years. The coronary artery lesions included ostial stenosis in 2 patients and main branch stenosis in 2, but both types of lesion were isolated. The latter patients were older and had coronary lesions like arteriosclerosis on angiogram. Myocardial infarction and congestive heart failure were not present, but a severe coarctation of the aorta was observed in the latter. It was suggested that coronary artery disease might not be rare past middle age, and might include coronary ostial stenosis caused by aortitis and coronary main branch stenosis probably based on secondary arteriosclerosis whose onset was past middle age.

Adult↗

[Pre-ejection flow in the left ventricular outflow tract: a pulsed Doppler echocardiographic study].

Pre-ejection flow (PEF) has been recognized as the flow of short duration toward the cardiac base in the left ventricular outflow tract. In the present study, PEF was analyzed by pulsed Doppler echocardiography to determine the contribution of left ventricular contraction to the genesis of PEF. The study subjects consisted of 20 patients with lone atrial fibrillation (Af) and 30 patients with premature ventricular contractions (PVC) without other cardiovascular diseases. Phonocardiogram and electrocardiogram were simultaneously recorded with Doppler signal of PEF. PEF was clearly detected in only 18 patients with PVC; in the remaining 12, it was not recorded or could not be differentiated from the signals of the preceding left ventricular diastolic filling. Results were as follows: 1. PEF in the cases with sinus rhythm appeared before the Q wave; whereas, it appeared after the Q wave in the cases with Af or PVC, and the peak of PEF coincided with the first heart sound on the phonocardiogram. 2. The duration of PEF was 93.6 +/- 15.4 msec in sinus rhythm, 60.6 +/- 14.2 msec in Af, and 87.5 +/- 19.4 msec in PVC. 3. Peak velocities of PEF in Af and PVC were significantly less than peak velocity of PEF in sinus rhythm. 4. Peak velocity of PEF in PVC with left bundle branch block tended to be less than that in PVC with right bundle branch block.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Fibrillation↗

[Comparison of two-dimensional echocardiography and Tl-201 SPECT in the evaluation of ischemic heart disease].

To ascertain the influence of severity of coronary stenosis and the presence or absence of collateral circulations on echocardiographic (2DE) asynergy or abnormal myocardial perfusion by exercise Tl-201 SPECT, we performed a correlative study of 40 patients undergoing coronary angiography, including 27 with myocardial infarction and 13 with angina pectoris, whose mean age was 55 years. Each view of the left ventricle (LV) obtained by both methods was assigned to five segments; i.e., anterior, septal, inferior, lateral and apical. The correlation of abnormal segments was investigated using both methods. The segments showing a severe perfusion defect coincided those with severe asynergy. Among 116 segments with normal perfusion, 99 (85%) revealed normal wall motion, but the remaining 15% showed asynergy. Among 84 segments with abnormal myocardial perfusion, 26 (31%) had normal wall motion, and most of these were non-infarcted regions. Concerning the severity of coronary artery stenosis, greater than 99% coronary arterial stenoses existed in most of the segments showing a complete defect or incomplete redistribution on Tl-201 SPECT and akinesis or hypokinesis on 2DE. Collaterals were observed in 22% of the segments with a complete defect and 66% of segments with incomplete redistribution; whereas, there was no significant correlation between the severity of LV wall motion abnormality and the presence or absence of collaterals. The severity of asynergy is possibly related to the severity of abnormal myocardial perfusion, however, asynergy could occur at the site of ischemic regions where Tl-201 SPECT can not detect the abnormalities. In patients with myocardial infarction who show incomplete redistribution by exercise Tl-201 SPECT, temporal ischemia of collaterals might cause such a perfusion abnormality.

Adult↗

Biological effect of orally active platelet-activating factor receptor antagonist SM-10661.

SM-10661 [(+/-)-(cis)-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl] displayed marked in vitro inhibition of rabbit platelet aggregation induced by 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (alkyl-PAF), 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16-PAF), and 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine, with IC50, values of 5.50, 5.94, and 3.68 microM, respectively. It also inhibited alkyl-PAF-induced aggregation of human platelets with an IC50 of 3.00 microM, but it did not inhibit platelet aggregation induced by ADP, collagen, arachidonic acid, the thromboxane A2 agonist U46619, or the Ca ionophore A23187, at concentrations up to 400 microM. Furthermore, SM-10661 antagonized [3H]-C16-PAF binding to rabbit platelets competitively, with an IC50 of 1.0 microM. SM-10661 protected against alkyl-PAF-induced lethality in mice with an ID50 of 6.0 mg/kg intravenously or 24 mg/kg orally. In guinea pig, SM-10661 inhibited the alkyl-PAF (0.1 micrograms/kg)-induced increase in bronchial pressure, with an ID50 of 0.7 mg/kg intravenously or 15 mg/kg orally. Bronchial hyperreactivity to bombesin after the infusion of alkyl-PAF was also inhibited dose-dependently by the infusion of SM-10661, with an ID50 of 25 mg/kg. In addition, SM-10661 inhibited alkyl-PAF (0.01 micrograms/kg)-induced hypotension in rats, with an ID50 of 0.36 mg/kg intravenously or 33 mg/kg orally. SM-10661, when given orally, showed rapid absorption and good duration of pharmacological activity in rats and rabbits.

Administration, Oral↗

Coronary artery aneurysms and congestive heart failure--possible long-term course of Kawasaki disease in an adult--a case report.

Multiple coronary artery aneurysms, rarely seen in patients with atherosclerotic heart disease, can be frequently observed in children with Kawasaki disease. However, their long-term clinical courses still remain obscure. A thirty-nine-year-old male came to our clinic because of congestive heart failure. A left ventriculogram revealed highly reduced wall motion. A coronary angiogram showed left main trunk aneurysm with complete occlusion of the left anterior descending artery and ramification of the right coronary artery close to the ostium. Six months after discharge, he died suddenly. On autopsy, aneurysms were observed in the left main trunk and right coronary artery, together with an old anteroseptal myocardial infarction. Although he did not have a clear history of febrile disease in childhood, he was highly suspected to be a long-term survivor of Kawasaki disease because of the unique form and distribution of the coronary artery aneurysms.

Adult↗