Left ventricular outflow obstruction caused by mitral ring calcification.
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Biomedical subjects
Publications and source records attributed to K Iga.
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A quantitative analysis of glutamate in brain dialysate was made by using an enzymatic cycling technique. This method made it possible to measure the concentration of glutamate in dialysate collected at 30-s intervals. Dialysates were collected from Mongolian gerbil hippocampus before, during, and after two 90-s ischemic insults at an interval of 5 min. An extracellular increase in levels of glutamate was already observed in samples collected during a 30-60 s period after the onset of each ischemia, and the levels of glutamate were maximal at the end of each period of ischemia (approximately a fourfold increase). The increased levels of glutamate rapidly returned almost to preischemic levels by 30 s of recirculation. This method will provide more precise information about temporal changes in the extracellular glutamate concentration in the brain during ischemia.
To obtain information as to a suitable formulation of ethyl 2-chloro-3-[4-(2-methyl-2-phenylpropyloxy)-phenyl]propionate (AL-294), an antihyperlipidemic drug of low water solubility, the bioavailability after its oral administration in various dosage forms was evaluated in rats and dogs. After AL-294 was administered orally, AL-294 acid (2-chloro-3-[4-(2-methyl-2-phenylpropyloxy)phenyl]propionic acid), which is a metabolite of AL-294, was detected in the plasma. Therefore, absorbability of AL-294 was evaluated using plasma AL-294 acid levels. AL-294 in an oil solution or in a gelatin capsule showed poor absorption, whereas it's absorption was greatly enhanced in the form of an emulsion. The postprandial administration also showed better absorption. The elimination rate of AL-294 acid from the plasma after oral administration of the emulsion was similar to that after intravenous administration of a sodium salt of AL-294 acid.
The main absorption site of ethyl 2-chloro-3-[4-(2-methyl-2-phenylpropyloxy)phenyl]propionate (AL-294) in rats was the upper portion of the small intestine. Both AL-294 and AL-294 acid (2-chloro-3-[4-(2-methyl-2-phenylpropyloxy)phenyl]propionic acid), a hydrolyzed form of AL-294, were absorbed in a smaller quantity under the bile fistula condition (pancreatic juice and bile were excluded). Compared with the absorption of AL-294 as an emulsion under the sham operation condition, the absorption of AL-294 as the emulsion decreased under the condition where only pancreatic juice was excluded. The bioavailability under this condition was very similar to that under the bile fistula condition, whereas the absorption of AL-294 acid did not decrease when the pancreatic juice was excluded. From these results, the absorption mechanism of AL-294 is considered as follows: AL-294 was hydrolyzed to AL-294 acid by lipase in pancreatic juice, then AL-294 acid was solubilized with bile salts to form mixed micelles in the intestinal lumen. AL-294 acid from this form was easily absorbed into the systemic circulation. Absorption of AL-294 increased when the particle size of the emulsion was smaller. The reason was assumed to be that the smaller particle size offered the greater oil-water interface for lipase activity against AL-294.
The left ventricular filling pattern was studied by pulsed Doppler echocardiography in 13 congestive heart failure patients with normal sinus rhythm. The first study was done when congestive heart failure was present; the second after the signs and symptoms of congestive heart failure disappeared. In 12 of the 13 patients, the peak mitral flow velocity in atrial systole (PFVA) increased after the congestive heart failure disappeared (mean increase from 50.5 cm/sec to 74.8 cm/sec : p = 0.0001, paired t test), and the peak mitral flow velocity in early diastole (PFVE) decreased significantly in all 8 patients in whom secondary mitral regurgitation became less severe after improvement of congestive heart failure (mean decrease from 90.8 cm/sec to 52.0 cm/sec : p = 0.0001, paired t test). The ratio of PFVA to PFVE (PFVA/PFVE) increased in all cases after the congestive heart failure improved (mean increase from 0.59 to 1.33 : p = 0.0001, paired t test). The PFVA/PFVE is a simple index of left ventricular diastolic function. A PFVA/PFVE greater than one indicates disturbed left ventricular diastolic function. However, when the PFVA/PFVE is in a normal range for the patients' age ("pseudo-normalization") and is accompanied by impaired left ventricular systolic function in congestive heart failure, markedly increased left ventricular end-diastolic pressure must be considered.
A grade 4/6 systolic murmur, systolic anterior motion of the mitral valve (SAM), and severe mitral regurgitation (MR) documented by two-dimensional Doppler echocardiography developed suddenly on the structurally normal heart of a patient with idiopathic portal hypertension. The patient did not have signs of congestive heart failure and the aforementioned phenomenon disappeared completely when the patient was in hepatic failure. This could be explained by a change in circulating blood volume either by gastrointestinal hemorrhage or hepatic failure.
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The release of cisplatin (CDDP) encapsulated in temperature-sensitive unilamellar liposomes to murine SCC VII carcinoma by localized hyperthermia and the effects of the treatment on tumor growth were studied. A transition temperature of the temperature-sensitive liposomes containing cisplatin (LIP-CDDP) was 41 degrees C. Twenty-four hours after injection of LIP-CDDP, the heated tumors (42 degrees C, 60 min) contained 3.3 times more CDDP than the unheated tumors receiving free CDDP. Although the uptake of liposome-associated CDDP by liver was approximately threefold greater at 1.5 h after injection than uptake of free CDDP, it decreased about 50% over a 24-h period. No difference in uptake of the two forms of CDDP by kidney was observed. The combination of LIP-CDDP and localized heating at 42 or 43 degrees C was more effective relative to the amount of CDDP in delaying tumor growth than that of free CDDP and hyperthermia. Treatment with LIP-CDDP plus local heating resulted in a dose-modifying factor of 5.3 when compared with free CDDP and no hyperthermia. The dose-modifying factor was 2.8 when treatment with LIP-CDDP and heat was compared with treatment with free CDDP and heat. Thus CDDP could be released selectively from the temperature-sensitive liposomes by heat and resulted in both a greater uptake of the drug and a delay in tumor growth.
We studied five cases of atrial fibrillation in the elderly showing severely decreased exercise tolerance (NYHA III) and normal left ventricular function. There were no signs of classical tricuspid regurgitation. Both atria were enlarged and right ventricular sizes were shown by two-dimensional echocardiography to have mildly increased. Two-dimensional Doppler echocardiography revealed severe tricupid regurgitation but at a maximal velocity less than 2.3 m/sec, meaning that right ventricular pressure was not increased. Cardiac output (CO) and circulating blood volume (BV), measured by radiocardiography showed CO to have decreased and BV to have increased. No intracardiac shunt was detected. The cause of this decreased exercise tolerance in the group in our study is thought to be right ventricular dysfunction due to the aging process. This also occurs in a similar pattern in younger people who have arrhythmogenic right ventricular dysplasia (ARVD), Uhl's disease, or right ventricular dilated cardiomyopathy.
Excessive catecholamine levels can cause myocardial damage in experimental animals. Similar observations have been made in humans following autopsy for pheochromocytoma. However, whether catecholamine crises are reversible or not remains uncertain. We report here a case in which pheochromocytoma manifested as acute pulmonary edema during an operation. Serial echocardiograms revealed that the depressed motion of the left ventricular wall was reversed after tumor removal. The plasma catecholamine level was extraordinarily high during the episode of acute pulmonary edema, and it seems that catecholamines in high concentration can directly damage the myocardium.
A method affording direct estimation of the drug absorption rate from blood level data using arbitrary time intervals has been derived based on the staircase input principle. In the derivation, the drug was assumed to follow linear kinetics where the plasma concentration of the drug after an impulse input is expressed by a multiexponential function. Drug absorption was assumed to occur at a constant rate during each subsequent sampling interval. The absorption rate profiles obtained by the method using several numerical examples were expressed as a set of rectangular pulses. Divergence in the profiles reflected blood sampling measurement errors rather than errors due to the deconvolution. Smoothing of the rate profiles by calculating the mean of the absorption rates between adjacent time intervals gave realistic results. Absorption rate profiles for theophylline obtained by the method using published data gave information on the initiation and termination of the absorption as well as the extent of absorption from the dosage form.
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The effect of ethyl myristate on the release rate of 4-hexylresorcinol from petrolatum base was studied at pH 7.4 and 37 degrees. 4-Hexylresorcinol was analyzed spectrophotometrically at 278 nm. The release rate of hexylresorcinol from the ointments was directly proportional to the square root of time and depended on the percentage of ethyl myristate in the ointment base. For 0, 0.5, 1, 3, and 5% of ethyl myristate, the release rates were 29.6, 35.4, 38.3, 55.7, and 70.0 micrograms/hr1/2/cm2, respectively. The solubility of hexylresorcinol in the petrolatum base was determined as a function of ethyl myristate using partitioning techniques. The enhancement in hexylresorcinol solubility was rationalized on the basis of 1:1 and 1:2 complexes between hexylresorcinol and ethyl myristate. The complexation constants of these complexes were estimated to be 10 M-1 and 206.1 M-2, respectively. The diffusion coefficient of hexylresorcinol in the petrolatum base was estimated to be 1.31 x 10(-8) cm2/sec.
Interactions of phenolic compounds 4-hexylresorcinol and 3,4-dimethylphenol with esters were studied using hexane-ester cosolvent systems by both phase solubility and partitioning methods. The data obtained by the phase solubility method were variable and could not be analyzed by any mathematical model. The data obtained by the partitioning method, however, strongly suggest that 4-hexylresorcinol forms 1:1 and 1:2 complexes with the esters in hexane, while 3,4-dimethylphenol forms only 1:1 complexes with the same esters.
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Plaque formation and gingival inflammation were found in ODU plaque-susceptible rats. A study was performed to determine the relationship between the presence of bradykinin in gingival tissue and the inflammatory capacity of rat plaque. Bradykinin content in gingival tissue and the bradykinin inactivating activity of dental plaque of 12-month-old ODU rats were measured. The presence of bradykinin was observed in the gingival tissue of the ODU rat and a bradykinin inactivating factor was found in the rat plaque. The factor was destroyed at 60 degrees C for 30 minutes, at pH 1.5 or by treatment with perchloric acid. The optimum pH of the factor was approximately 8.0. Chelate reagents, such as O-phenanthroline and EDTA . 4Na, strongly inhibited the bradykinin inactivating factor. The protease inhibitor, Trasylol, also inhibited this factor. The SH reagent, L-cysteine, inhibited weakly and Zn++ inhibited less. The investigation suggested that the rat plaque posseses the ability to inactivate bradykinin and plays an important role in modifying the inflammatory response caused by bradykinin in gingival tissue.
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