Biomedical subjects
Publications and source records attributed to Y Uchida.
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There have been no report on concentrations in human lung tissue of aminoglycoside antibiotics which are frequently used in combination with cephem antibiotics in the treatment of severe respiratory infections. The authors examined lung tissue concentration of astromicin (ASTM) during clinical trials in thoracotomized patients using intravenous drip infusion just before operation. And the following conclusions have been obtained: 1. The average peak serum level obtained upon intravenous drip infusion of ASTM 200 mg for 1 hour just before operation was 11.2 micrograms/ml at 1 hour after starting the administration and half-life of ASTM in beta phase was 2.90 hours. 2. ASTM concentrations in the lung tissue upon 1 hour intravenous drip infusion just before operation at a dose level of 200 mg reached a maximum at 2 hours after the start of the administration averaging 7.7 micrograms/ml and were 27.7-68.8% of serum peak level. 3. Bronchiolar concentrations of ASTM 200 mg upon 1 hour intravenous drip infusion just before operation were 33.0-72.3% of peak serum level. These concentrations appear to be sufficient for the treatment of target infections. 4. The 1 hour intravenous drip infusion of ASTM 200 mg appeared to be clinically safety and useful as was the intramuscular injection of ASTM 200 mg.
Many nasal sprays used in the treatment of rhinitis contain a steroidal agent, giving rise to fear of side effects when they are used frequently and continually. Accordingly, we undertook the development of a nasal spray containing oxaprozin, a nonsteroidal anti-inflammatory agent. Suitable discharge pressure and surfactants were determined by applying trial aerosols to human subjects in "feeling" tests to assess approval rating. Other tests showed that about 80% of the expelled oxaprozin was released into the nasal cavity, and that the chosen formulation caused only a low level of irritation to the nasal mucosa. Most of the aerosol particles were found to adhere to Kiesselbach's area and the frontal region of the inferior concha, which are the major areas where inflammation and nasal haemorrhage occur. When the nasal spray was administered to 50 patients, a sufficient therapeutic effect was achieved, especially in the treatment of nasal haemorrhage, and side effects have not yet been detected.
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[125I]-Nerve growth factor (NGF) binding was studied in superior cervical ganglia from mice 4-7 months and 24-27 months of age. Scatchard analysis demonstrated losses of both high and low affinity components of NGF receptor. These results indicate loss of NGF receptors may lead to the diminished responsiveness to NGF in aged sympathetic ganglion neurons.
Several molecular species of monohexaosyl glycolipids and ceramides were analyzed as their benzoyl derivatives by high-performance liquid chromatography on a silica column with mixtures of dioxane and hexane as eluents. Monohexaosyl glycolipid derivatives were classified according to their hydrophobic structures, and ceramides were separated based on the fatty acid groups and the long-chain bases. The method allowed us to observe the heterogeneities in the molecular species of cerebrosides and ceramides from the epidermis and dermis of the guinea pig, and clear differences in the molecular species were observed between the different regions.
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Inoue-Melnick virus (IMV) was isolated from six of seven human meningioma-derived cell cultures, while the virus was not isolated from six other brain tumor cell cultures. Sera of 145 consecutive neurosurgical inpatients were tested for IMV-neutralizing antibody. Of 26 patients with meningioma, 22 were positive for IMV antibody (84.6%). Of the remaining 119 patients, 16 were positive.
Cobrotoxin-binding protein was isolated by affinity chromatography from human thymoma which had been surgically removed from patients with myasthenia gravis. The protein was composed of polypeptides with a molecular mass of 40, 51, 65, and 74 kilodaltons as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulphate. Isoelectric focusing of the protein gave pI values of 5.2-5.6 and 11. This is the first report of the isolation of the protein from human thymoma. These findings suggest that the cobrotoxin-binding protein from human thymoma patients with myasthenia gravis has subunits similar to those of fish electric organs or mammalian muscles.
Reported in this paper are two cases of peptic ulcer which developed in the gastric tube used for esophageal replacement following esophagectomy for esophageal tumors in adults. The results of our cases suggest that acid secretion from the mucosa of the gastric tube, in spite of truncal vagotomy and the state of the tube, seems to play important roles in the pathogenesis of peptic ulcer of the gastric tube after esophageal replacement, even though circulatory disturbances, due to postoperative irradiation and gastric tube formation, have been suspected as the cause. Therefore, in those cases of gastric tube stasis, surgical drainage of the gastric tube should be performed.
Angiography and angioscopy were used to examine arterial luminal changes induced by experimental vasospasm. The right common carotid artery of the dog was perfused with Krebs-Henseleit solution at a constant pressure, 3,4-diaminopyridine (DAP), a selective potassium channel blocker was applied on the adventitia, and the luminal changes were observed with angiography and angioscopy. Angiographically vasospasm (defined as a reduction in the internal diameter to less than 50% of the control value) was always induced by the topical application of 5 X 10(-1) mol/L DAP. The internal diameter decreased to 25% +/- 7% (mean +/- standard error, n = 6) 15 minutes after the application. The vasospasms propagated 2.7 +/- 0.6 and 1.1 +/- 0.3 cm downstream and upstream, respectively. Angioscopy showed that the lumen narrowed gradually and concentrically. Perfusion of the artery during vasospasm for 15 minutes with a backflow of blood from the contralateral artery resulted in thrombosis at the spastic segment. The results indicate that carotid vasospasm can be constantly induced by DAP, thrombosis occurs in the spastic artery, and angioscopy is useful for serial observation of the luminal changes induced by vasospasm.
Percutaneous transluminal coronary angioscopy was performed during routine coronary angiography in seven patients and during PTCA in one patient with ischemic heart disease. A flexible fiberscope with an external diameter of 1.4 mm was introduced through an 8F or 9F guiding catheter used for PTCA into the coronary arteries. Warmed saline solution (15 to 20 ml) was injected through the guiding catheter into the coronary arteries for replacement of blood. Twenty-one of the 31 coronary segments were visualized and photographed on color cinefilms. The lumen of the atherosclerotic segment showed narrowing with smooth surface or with spiral folds. PTCA caused dilatation of the stenosed segment with scattered thin thrombi. These findings indicate the usefulness of angioscopy to observe luminal changes in the coronary arteries of patients with ischemic heart disease.
We produced arterial thrombi that simulated the clinical condition in canine iliac arteries by endothelial denudation and partial occlusion. The processes of thrombus formation and thrombolysis were examined by vascular fiberscope. Laminar mural thrombi developed in all 21 preparations 10 minutes after blood reperfusion, with stenosis formation. Over 50% luminal obstruction with thrombi occurred in 10 preparations 30 minutes after inducing stenosis. Total occlusion with thrombi occurred in four preparation (31%) at 1 hour, and in all nine at 3 hours after inducing stenosis. Usually, red thrombus at the denudated region grew in size distal to the sited of stenosis. Histologically, thrombi of less than 1 hour duration consisted of a loose fibrin network and those of over 3 hours' duration consisted of a dense fibrin network. Infusion of 144,000 IU of urokinase (UK) reduced the size of thrombi less than 1 hour old during fiberoptic observation. However, UK infusion of similar dose failed to recanalize two of four preparations with 3-hour-old thrombi. In conclusion, arterial thrombi that closely simulate those observed clinically can be made by endothelial denudation and partial occlusion, and the vascular fiberscope provides a useful method for analysis of thrombosis and thrombolysis.
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Plasma concentrations of immunoreactive alpha-human atrial natriuretic polypeptide (i alpha-hANP) and cyclic guanosine monophosphate (cGMP) were measured in 70 patients with heart disease. Plasma concentrations of i alpha-hANP were directly related to the severity of heart disease (F = 29.61, p less than 0.001). Plasma concentrations of i alpha-hANP were well correlated with pulmonary capillary wedge pressure (PCWP; r = 0.64, p less than 0.001), mean pulmonary arterial pressure (PAP; r = 0.62, p less than 0.001), and mean right atrial pressure (RAP; r = 0.75, p less than 0.001). Plasma concentrations of cGMP were also directly related to the severity of heart disease (F = 13.61, p less than 0.001) and highly correlated with plasma concentrations of i alpha-hANP (r = 0.73, p less than 0.001). Plasma concentrations of cGMP were also closely correlated with PCWP (r = 0.69, p less than 0.001), mean PAP (r = 0.61, p less than 0.001), and mean RAP (r = 0.60, p less than 0.001). The i alpha-hANP concentrations of plasma samples obtained from the coronary sinus were approximately fourfold higher than those of samples obtained from the pulmonary artery, whereas cGMP concentrations were comparable in plasma samples obtained from either site. Elevation of cGMP concentrations following intravenous infusion of synthetic alpha-hANP was comparable in plasma samples obtained from the coronary sinus and the pulmonary artery. These findings suggest that elevated plasma concentrations of i alpha-hANP in cardiac patients result from an increase in the secretion of ANPs, which is probably accelerated by elevation of right or left atrial pressure, and that plasma concentrations of cGMP reflect circulating levels of alpha-hANP.
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1 A new synthetic bradykinin analogue was found to be an antagonist of bradykinin-induced vascular permeability in rabbit skin. It was effective in equimolar concentrations. 2 These analogues also antagonized the action of bradykinin in contracting the guinea-pig isolated ileum. The mean pA2 values of five different antagonists ranged from 5.3-6.4 respectively, on this preparation. 3 Our observations, together with those of others suggest that these antagonists act on the same receptor types, viz., B2, in rabbit blood vessels and in smooth muscle of guinea-pig ileum. 4 Our results support the view that the way is now promising for the synthesis of potent specific antagonists of bradykinin for experimental and therapeutic use.
In this study we reevaluated whether the sole cause of mitral valve prolapse (MVP) and aortic valve prolapse (AVP) is myxomatous degeneration. Forty-two surgical cases of prolapsed valves with mitral and/or aortic regurgitation were reviewed (AVP in nine, MVP in 27, and combined AVP and MVP [CVP] in six). On microscopic examination, myxomatous degeneration was observed in 20 patients, including six with AVP, 13 with MVP, and one with CVP. In the other 22 patients, including three with AVP, 14 with MVP, and five with CVP, microscopic examination revealed fibrosis with vascularization and scattered infiltration of inflammatory round cells caused by postinflammatory changes with or without chronic inflammation. We coined the term "postinflammatory valve prolapse" (PIVP) to describe these valves. Both postinflammatory and myxomatous degeneration were observed in seven patients with floppy mitral valves attributable to PIVP. Rupture of chordae tendineae was present in six patients with myxomatous mitral valve and three with PIVP. Seven patients with PIVP had a history of rheumatic fever. The results suggest that valvular prolapse is produced not only by myxomatous degeneration but also by postinflammatory changes, including those caused by rheumatic fever.