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We examined the effect of high potassium (K) diet on oxidative stress to endothelium in hypertensive rats. Five-week-old stroke-prone spontaneously hypertensive rats (SHRsp) were fed a 5% high NaCl diet containing either 0.5% normal K (n = 28) or 2.1% high K (n = 19) for 6 weeks, and lipid peroxides in the aortic intima and plasma were measured. Lipid peroxides were extracted into an organic solvent to avoid the interference of carbohydrates or glycoproteins, and malondialdehyde (MDA) produced from lipid peroxides by acid-heating was measured by its reaction to thiobarbituric acid. The antioxidant butylated hydroxytoluene prevented spurious lipid peroxide formation during the whole procedure, and optimum Fe3+ allowed a maximum MDA production from lipid peroxides. The high K SHRsp showed lower lipid peroxide levels than the normal K SHRsp both in the intima (5.6 +/- 0.3 vs. 7.2 +/- 0.4 nmol MDA/mg fatty acids, p < 0.003) and plasma (0.91 +/- 0.08 vs. 1.46 +/- 0.10 nmol MDA/ml, p < 0.001). Mean arterial pressure was slightly lower by 13 mmHg in the high K SHRsp, but these differences were still obvious even when we compared groups of rats with precisely matching blood pressures. These results indicate that high K diets reduce oxidative stress on the endothelium of high NaCl-fed SHRsp independently of blood pressure changes. This effect may be involved in the mechanism by which high K diets protect endothelium and reduce stroke incidence in hypertensive animals. Thus, we improved the method of lipid peroxide measurement and propose the protective effects of high K diet against oxidative stress to endothelium in hypertension animals.

A computer simulation of the dispensing work performed in a hospital pharmacy was undertaken, based on analysis data from a work-sampling method and utilizing a personal computer. As a result it was found to be possible to estimate the complete work volume of a day based on the number of prescriptions in the day, and hence to predict fairly precisely the number of pharmacists required to complete that work. The method also enables the users to assign the optimum number of staff for dispensing duties according to the estimated number of prescriptions and the optimum waiting time of patients. A correlation has been noted between the total residence time of prescriptions and the mean waiting time of patients. Using this simple and effective technique to efficiently assign personnel makes it possible to cope with an increasing workload and limited number of staff.

Increase in left ventricular weight is an important risk factor for the incidence of cardiovascular diseases, and reduction in diastolic function of the left ventricle is an early marker for cardiac dysfunction. Factors related to the left ventricular mass and diastolic function were analyzed in middle-aged normotensive men.The subjects were 126 normotensive men aged 49 +/- 1 years who were hospitalized for health-checkup. In addition to physical examination and routine laboratory tests, echocardiography including the pulse-Doppler method was performed and urinary electrolyte excretions, plasma angiotensin II, plasma noradrenaline and the angiotensin converting enzyme genotype were examined.Left ventricular mass index was positively correlated with mean blood pressure (r = 0.249, p0.006) and body mass index (r = 0.279, p0.002). With regard to the index of left ventricular diastolic dysfunction, the late to early peak transmitral flow velocity ratio (A/E) was positively correlated with age (r = 0.465, p0.001) and urinary sodium excretion (r = 0.240, p0.007). Neither left ventricular mass index or A/E was affected by the angiotensin converting enzyme genotype and was not significantly correlated with plasma angiotensin II or noradrenaline.Increase in left ventricular mass is influenced by blood pressure and obesity, whereas reduction in left ventricular diastolic function is affected by greater age and salt intake.

Congenital nephrogenic diabetes insipidus is a rare disorder in which the kidney is insensitive to the antidiuretic hormone, vasopressin. In most cases, a mutation in the vasopressin type 2(V2) receptor gene is the genetic cause of the disease. So far, few cases of congenital nephrogenic diabetes insipidus with hypertension have been reported. We report one male case of congenital nephrogenic diabetes insipidus accompanied by hypertension. The patient was a 24-year-old man who had suffered from polyuria and polydipsia since infancy and had been found to have hypertension at about 16 years. He was admitted to hospital in May 2000 for investigation of polyuria and hypertension with a high plasma level of renin activity of 10.4 ng/ml/hr. On physical examination, the blood pressure was 150/90 mmHg and the daily urinary output was 18.5 l. There was no change in urine volume and urine osmolality after an intramascular injection of vasopressin and water deprivation. The blood pressure and plasma renin activity were increased from 127/73 mmHg to 146/87 mmHg and from 4.9 ng/ml/hr to 6.1 ng/ml/hr, respectively, by a 4-hour dehydration test. He was found to have a C-to-T transition at nucleotide position 675 by sequencing analysis of the V2 receptor gene. After administration of hydrochlorothiazide, both the blood pressure and urine volume were reduced. Consequently, it was suggested that activation of the renin-angiotensin system by dehydration, at least in part, contributed to high blood pressure in this case.

The effects of obesity on target organ injuries and cardiovascular risk factors were examined in hypertensive subjects. The subjects were 22 obese (OB-HT) and 54 nonobese (NO-HT) men with never-treated essential hypertension, and 37 obese (OB-NT) and 50 nonobese (NO-NT) normotensive men. In these 4 groups with the average age of about 50 years, we evaluated serum lipids, glucose tolerance, and hypertensive organ injuries in the heart, kidney, and optic fundus. Although the fasting blood glucose levels were similar in the 4 groups, the area under the blood glucose curve after 75 g glucose ingestion (NO-NT 15.6, OB-NT 17.5, NO-HT 15.8, OB-HT 17.6 x 10(3) mg/dl.min; p0.02) and the fast serum insulin level (NO-NT 7.3, OB-NT 10.1, NO-HT 7.7, OB-HT 12.2 mU/l; p0.001) were increased in obese men. In OB-HT, serum HDL-cholesterol was decreased (-11%, p0.05) and triglycerides were increased (+ 58%, p0.01) comparing with NO-NT. The incidence of electrocardiographic left ventricular hypertrophy was not significantly different among the 4 groups, however, urinary albumin excretion was increased in OB-HT (NO-NT 3.0, OB-NT 3.4, NO-HT 3.6, OB-HT 4.3 mg/g creatinine; p0.05) and sclerotic lesions of the retinal arteries were observed even in normotensive OB-NT. These data suggest that obesity unfavorably alters lipid and glucose metabolism, and facilitates organ injuries such as arteriosclerosis and renal dysfunction in hypertensive subjects.

We propose the following guidelines for treatment of hypertension in the elderly. 1. Indications for Treatment. 1) Age: Lifestyle modification is recommended for patients aged 85 years and older. Antihypertensive therapy should be limited to patients in whom the merit of the treatment is obvious. 2) Blood pressure: Systolic BP160 mmHg, diastolic BP90 approximately 10 mmHg. Systolic BPage + 100 mmHg for those aged 70 years and older. Patients with mild hypertension (140-160/ 90-95 mmHg) associated with cardiovascular disease should be considered for antihypertensive drug therapy. 2. Goal of Therapy for BP: The goal BP in elderly patients is higher than that in younger patients (BP reduction of 10-20 mmHg for systolic BP and 5-10 mmHg for diastolic BP). In general, 140-160/90 mmHg is recommended as the goal. However, lowering the BP below 150/85 should be done with caution. 3. Rate of Lowering BP: Start with half the usual dose, observe at the same dose for at least four weeks, and reach the target BP over two months. Increasing the dose of antihypertensive drugs should be done very slowly. 4. Lifestyle Modification: 1) Dietary modification: (1) Reduction of sodium intake is highly effective in elderly patients due to their high salt-sensitivity. NaCl intake of less than 10 g/day is recommended. Serum Na+ should be occasionally measured. (2) Potassium supplementation is recommended, but with caution in patients with renal insufficiency. (3) Sufficient intake of calcium and magnesium is recommended. (4) Reduce saturated fatty acids. Intake of fish is recommended. (2) Regular physical activity: Recommended exercise for patients aged 60 years and older: peak heart rate 110/minute, for 30-40 minutes a day, 3-5 days a week. (3) Weight reduction. (4) Moderation of alcohol intake, smoking cessation. 5. Pharmacologic Treatment: 1) Initial drug therapy. First choice: Long-acting (once or twice a day) Ca antagonists or ACE inhibitors. Second choice: Thiazide diuretics (combined with potassium-sparing diuretic). 2) Combination therapy. (1) For patients without complications, either of the following is recommended. i) Ca antagoinst + ACE inhibitor, ii) ACE inhibitor + Ca antagonist (or low-dose diuretics), iii) diuretic + Ca antagonist (or ACE inhibitor), iv) beta-blockers, alpha 1-blockers, alpha + beta blockers can be used according to the patho-physiological state of the patient. (2) For patients with complications. Drug(s) should be selected according to each complication. 3) Relatively contraindicated drugs. beta-Blockers and alpha 1-blockers are relatively contraindicated in elderly patients with hypertension in Japan. Centrally acting agents such as reserpine, methyldopa and clonidine are also relatively contraindicated beta-Blockers are contraindicated in patients with congestive heart failure, arteriosclerosis obliterans, chronic obstructive pulmonary disease, diabetes mellitus (or glucose intolerance), or bradycardia. These conditions are often present in elderly subjects. Elderly subjects are susceptible to alpha 1-blocker-induced orthostatic hypotension, since their baroreceptor reflex is diminished. Orthostatic hypotension may cause falls and bone fractures in the elderly.

A very rare case of small bowel strangulation caused by herniation of a loop of ileum through a defect in the falciform ligament is reported. A 27-year-old woman in the 38 weeks and 5 days of pregnancy was admitted with a sudden onset of epigastralgia. Emergency laparotomy with cesarean section was performed. A strangulated loop of ileum was found to pass through a defect in the falciform ligament. The ligamentum teres was divided to release the obstruction and the irreversible strangulated loop was resected. The strangulation was considered to have occurred because a loop of small bowel compressed by gestational uterus passed through a congenital defect in the falciform ligament.

We investigated the role of the vasoconstrictors endothelin-1 (ET-1) and thromboxane in renal protection by the beta 1-selective adrenoceptor antagonist, bisoprolol, in Dahl salt-sensitive rats (Dahl S) and salt-resistant rats (Dahl R). Six-week bisoprolol treatment (20 mg/kg chow) reduced systolic blood pressure (SBP) by 14% in Dahl S rats fed a high-salt (4% NaCl) diet. This BP reduction was accompanied by a decrease in aortic wall thickness. ET-1 and thromboxane released from renal cortex was significantly decreased by 17 and 30% with bisoprolol, respectively. Other prostaglandin synthesis was unaffected. Renal function such as proteinuria, N-acetyl-beta-D-glucosaminidase (NAG) excretion, and glomerular filtration rate (GFR) was not influenced by bisoprolol. Morphologic investigation showed that bisoprolol significantly improved glomerular sclerosis by 29% and attenuated arterial damage by 71%, although tubular injury was not affected. The more severe the glomerulosclerotic lesions, the greater the generation of thromboxane and ET. The arterial lesions were positively correlated to thromboxane generation. These data indicate that long-term bisoprolol treatment reduces vasoconstrictive ET-1 and thromboxane generation and that these alterations may be partly responsible for the amelioration of glomerular and arterial injury in Dahl S rats.

In this study, we measured cross sectional areas of glomerular arterioles and glomerular volume in heminephrectomized spontaneously hypertensive rats (SHR) treated with a calcium antagonist, nisoldipine (NSL). We also examined the relevance of these parameters to the progression of hypertensive renal injury. Male 6-week-old SHR (n = 14) were heminephrectomized and divided into 2 groups. They were fed regular chow (control, n = 7) or chow containing 0.1% NSL (n = 7). After 12 weeks, urinary protein excretion (UpV) and systolic blood pressure (SBP) were measured. The control rats developed marked hypertension reaching 228 +/- 2 mmHg, and NSL lowered this by 27 mmHg (p0.001). NSL reduced UpV by 22% (p0.05). Microvascular cast of the kidney was prepared, and the cross sectional areas of the afferent and efferent arterioles as well as glomerular volume were measured using scanning electron microscopy. In the juxtamedullary and subcapsular glomeruli with minor abnormalities, the afferent arteriole was narrower and the glomerular volume was smaller in the NSL-treated rats than in the control rats. These results suggest that the calcium antagonist, NSL, offers the advantage of protecting kidney from hypertensive injury by reducing afferent arteriolar diameter, glomerular hypertrophy and intraglomerular pressure in heminephrectomized SHR.

Eosinophil chemotactic factors (ECFs) are thought to play an important role in the recruitment of eosinophils to parasitic inflammatory regions. ECF-A derived from mast cells, lymphokines from lymphocytes and ECFs from complements are well known as host-derived ECFs. On the other hand, ECF from parasites (ECF-P) and cytokines such as ESP (eosinophil stimulation promoter) and interleukin-5 are reported to be responsible for the eosinophil accumulation in parasitic inflammatory regions. In a series of our experiments using Anisakis larvae, we discovered a mechanism of eosinophil recruitment which could be accelerated by priming with ECF-P in parasite infected eosinophil phlegmon.

In order to examine the efficacy and safety of long-term erythropoietin (rHuEPO) therapy, 103 hemodialysis patients were treated with rHuEPO for their renal anemia and the effects were observed for 1 year. Within 3 or 4 months after starting the rHuEPO therapy, the hematocrit (Ht) value rose up to nearly 30% and the level was maintained thereafter by approximately 4500 IU per week of rHuEPO. Tachyphylaxis did not occur even after 1 year of rHuEPO treatment. Symptoms such as headache, dizziness or palpitation were markedly reduced with the improvement of anemia. Although blood pressure was modestly elevated (systolic by 9 mmHg, p0.01 and diastolic by 5 mmHg, p0.01 at 6-month-stage), only 1 patient was forced to stop the therapy. Moreover, the blood pressure was successfully controlled to the original level after 11 months. This blood pressure elevation was not related to the increase of Ht level nor the dose of rHuEPO. Serum protein, lipid, electrolytes and liver enzymes did not change during 1 year of rHuEPO therapy. These results indicate that rHuEPO treatment is effective and innocuous as a long-term therapy of renal anemia in hemodialysis patients.

When interleukin-2 alone or in combination with lymphokine-activated killer (LAK) cells is administered to patients with cancer, peripheral or local eosinophilia is frequently seen. To evaluate the role of eosinophils in this setting, we studied the functional changes of human eosinophils induced by the supernatant of LAK cell cultures. The chemotactic activity, change in chemiluminescence, superoxide production, expression of leukocyte integrins (CD11/CD18 family), and adherent activity to plastic dishes were investigated after stimulation of eosinophils with LAK cell culture supernatant. The chemotactic activity of eosinophils in the supernatant of LAK cell cultures was increased significantly, and this activity was chemotactic rather than chemokinetic by checkerboard analysis. Both chemiluminescence and superoxide production of stimulated eosinophils increased significantly compared with resting. In addition, eosinophil-adherent activity to plastic dishes was also increased. Among leukocyte integrins, CD11b expression on stimulated eosinophils increased. Moreover, eosinophil antibody-dependent cellular cytotoxicity against Raji cells was enhanced after stimulation with the supernatant of LAK cell cultures. These results suggest that the eosinophils activated by LAK cells may play an important role in the antitumor effect of interleukin-2/LAK cell therapy.

To investigate changes in left atrial morphology and dimensions during the cardiac cycle, the atrium was visualized by intravenous digital subtraction angiography (DSA). The study subjects consisted of 22 male patients whose average age was 54.5 +/- 8.6 years. They had ischemic heart disease without mitral valve disease and were in sinus rhythm. They were 11 patients with old myocardial infarction (OMI group) and 11 who had chest pain without evidence of infarction (AP group). DSA was performed in the continuous mode. Contrast material (35 ml) was injected at a rate of 18 ml/sec via a catheter in the superior vena cava and subtraction images were obtained at a speed of 30 frames/sec in the right anterior oblique projection. The left atrial and left ventricular margins were traced manually, their areas were calculated, and fractional changes in area were analyzed. The left ventricular ejection fraction (LVEF) was calculated by densitometry. Cardiac catheterization was performed in 16 patients and the left ventricular end-diastolic pressure (LVEDP) and mean pulmonary arterial wedge pressure (PAWP) were measured. The entire left atrium was clearly imaged using DSA. Phase analysis of the time-area curves in the right anterior oblique projection revealed that the left atrial area was maximal during left ventricular end-systole (%LA1 = 100%), it decreased during early left ventricular diastole (%LA2), and then increased slightly again during mid-diastole (%LA3). After left atrial contraction, the minimum area was obtained (%LA4). The left atrium showed a two-stage decrease in the area due to passive emptying and active contraction during left ventricular diastole. Passive emptying (%LA1-%LA2) was significantly less in the OMI group than in the AP group (6.3 +/- 3.6 vs 13.3 +/- 4.8%, p0.01, respectively). In all 22 subjects, passive emptying correlated with LVEF (r = 0.70, p0.001) and LVEDP (r = -0.58, p0.05). There was no difference in active contraction (%LA3-%LA4) between the 2 groups (26.0 +/- 5.7% in the OMI group, 28.2 +/- 8.4% in the AP group), and it did not correlate with LVEF or LVEDP. The ratio of passive emptying to active contraction [(%LA1-%LA2)/(%LA3-%LA4)] correlated with LVEF (r = 0.63, p0.01). These findings suggested that impaired left ventricular diastolic function and a relative increase in atrial contraction were present in patients with a lower LVEF. The %LA4 correlated with LVEDP and PAWP (r = 0.65, r = 0.63, p0.01, respectively). In conclusion, DSA proved to be a useful method for investigating left atrial morphology and function.

This study investigated the release of prostacyclin (PGI 2 ) and thromboxane A 2 (TXA 2 ) from the aortic walls of various experimental hypertensive rats, e.g. spontaneously hypertensive rats (SHR), Dahl salt-sensitive (Dahl S) rats, deoxycorticosterone (DOCA)-salt hypertensive rats and renovascular (2-kidney, 1-clip (2K1C) and 1-kidney, 1-clip (1K1C) hypertensive rats. The PGI 2 generation was increased significantly in these hypertensive models, irrespective of the hypertensive mechanisms, when they developed established hypertension. Dahl S rats, having an impaired PGI 2 production on a low salt diet, restored PGI 2 generating capacity to the control level of Dahl salt-resistant rats when they were fed a high salt diet and developed salt-induced hypertension. On the other hand, the TXA 2 generation in the vascular walls was enhanced particularly in rat models for genetic hypertension, and this system was unaltered in the models for secondary hypertension, e.g. DOCA-salt and renovascular hypertension. Thus, it is suggested that the elevation of blood pressure is associated with an increase in vascular PGI 2 production, and that the increased vascular TXA 2 production is a characteristic feature of genetic hypertension.

This paper reports the etiology and the findings of phonocardiograms and echocardiograms in four cases with mitral regurgitation caused by the redundant chordae. Redundancy of the chordae were determined by the surgeon during operation. The results were as follows: 1. The etiology of redundant chordae was either congenital, rheumatic, or mucoid degeneration. 2. Phonocardiographic findings of this condition are a holosystolic murmur accompanied by a diastolic rumble at the apex. 3. Two-dimensional echocardiogram shows holosystolic bulging of the mitral leaflet to which redundant chordae are attached. 4. The findings of the M-mode echocardiogram are multiple linear echoes and bowing of the mitral valve in systole.

To evaluate mitral valve function and its long-term outcome after open mitral commissurotomy (OMC), we examined 39 patients using Doppler echocardiography. There were 13 males and 26 females; who were examined a total of 83 times after the surgery at about one year intervals (seven to 240 months, averaging 78 months). We measured the velocity of transmitral blood flow using the continuous wave Doppler method (CWD), and the transmitral pressure half time (PHT), mean velocity (m V) and peak velocity (pV) were calculated. The presence and severity of mitral regurgitation (MR) were assessed by color flow mapping. 1. PHT gradually increased and significantly correlated (r = 0.63, p less than 0.001) with the months passed after OMC. The regression line of PHT in postoperative months was "PHT = 0.70 x PMo + 83" (PMo = postoperative months). The mV and pV tended to increase gradually, but did not significantly correlate with the months passed after the surgery. 2. Among the 39 patients, 28 (72%) had MR, and their severity was classified as 1+ in two, 2+ in 19, 3+ in six and 4+ in one. Among 21 patients who had no MR before OMC, MR appeared in 12 (57%), and its severity was classified as 1+ in one, 2+ in nine and 3+ in two. All five patients with preoperative MR had MR postoperatively, and their severity was classified as 1+ in one, 2+ in two and 3+ in two. The presence of the preoperative MR of the remaining 13 patients was unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

For a group of catechol amino-acids varying widely in acid strength and hydrophobicity, the effects of mobile phase composition, pH and ionic strength on their reversed-phase chromatographic separation have been determined, with phosphate buffer as mobile phase. Retention data were measured for 18 catecholamine derivatives. The retardation factors and retention behaviour of all the compounds tested could be explained in terms of the acid dissociation and tautomeric constants.

The macroionization constants and thermodynamic parameters of twelve commercial sulphonamides were determined by potentiometric titration at 15 degrees , 25 degrees and 35 degrees and by spectrophotometry at 25 degrees , in aqueous solution of ionic strength 0.1 (NaClO(4)). The microionization constants and the tautomeric constants (concentration ratios of zwitterion to uncharged or neutral species) were obtained according to the Edsall method combined with complementary tristimulus colorimetry. By utilizing the microionization constants, the species distribution as a function of pH were calculated for the three kinds of sulphonamides.

In view of the fact that stable echocardiograms are easily obtained during atrial pacing, pacing echocardiography was performed to evaluate the usefulness for detecting regional wall motion abnormalities during pacing-induced ischemia and to investigate the relationship between changes in the R wave and left ventricular dimension. The patients were 12 cases of angina pectoris (10 of coronary artery disease; CAD, and 2 of coronary patent aortic valvular disease; AVD) and 6 control cases. Simultaneous recording of two-dimensional and M-mode echocardiograms and electrocardiograms was done before, during and after the atrial pacing at increasing heart rate until angina appeared or the heart rate of at least 140/min was reached. In 12 angina cases, angina and ST depression were induced in 10 and 11, respectively. Excursion of the interventricular septum (IVS) decreased during pacing-induced ischemia in 6 of 7 CAD cases, in which the left anterior descending coronary artery was significantly stenosed (more than 75%). Excursion of the left ventricular posterior wall (LVPW) decreased during pacing-induced ischemia in 4 of 7 CAD cases, in which the vessels giving rise to posterior descending coronary artery were significantly stenosed (more than 75%). In 2 AVD cases, excursion of both IVS and LVPW decreased during ischemia. Left ventricular end-diastolic dimension (LVEDD) increased in only 2 angina cases, although R wave amplitude increased in 6 angina cases.

The nutritional and immune status were studied in advanced lung cancer patients receiving combined chemotherapy and an elemental diet to test the effectiveness of the latter. Parameters such as skin tests, lymphocyte count, total protein and albumin values, body weight, and nitrogen balance were improved or maintained by the administration of the elemental diet. A better response to chemotherapy was achieved in patients receiving the elemental diet. Elemental diet support is suggested as a useful addition to chemotherapy in advanced lung cancer.

This study assesses the diagnostic value of Lipiodol (iodized oil) and computed tomography (CT) in detecting hepatocellular carcinoma (HCC). Twenty-four patients who were suspected of having HCC received injections of a small amount of Lipiodol, along with an antitumor agent, in the hepatic artery following routine celiac angiography. CT scans obtained 7-10 days after Lipiodol administration demonstrated HCC in distinct contrast to the surrounding noncancerous parenchyma. In particular, the CT-Lipiodol procedure disclosed many small HCC lesions that were not shown by celiac angiography, scintigraphy, CT with and without contrast medium enhancement, and ultrasonography. Although this procedure may miss very small or highly fibrotic lesions, it is recommended for patients suspected of having HCC and for patients for whom hepatic resection is being considered.

The arid-base chemistry of tyrosine-containing peptides such as enkephalin, tyrosylglycylglycine, tyrosylglycine and analogous peptides is described. For each peptide and tyrosine derivative, microscopic and macroscopic acid dissociation constants and the thermodynamic parameters for proton dissociations were determined from pH-titrations and ultraviolet absorption spectra. The relative concentrations of various ionic forms for the peptides were calculated from the microscopic constants. The concentration ratio, represented by the tautomeric equilibrium constant (Kt), showed a definite relationship to structure.

We designed experiments to reveal the effects of a S2 serotonergic receptor antagonist, ketanserin, on the vascular eicosanoid system and the relevance to medial hyperplasia in spontaneously hypertensive rats (SHR). 2-week ketanserin treatment (5 mg/kg/day) significantly decreased systolic blood pressure by 7% when compared to untreated SHR. The blood pressure reduction was associated with a significant decrease in vascular thromboxane A2 (TXA2) generation and sustained prostacyclin (PGI2) production, thereby shifting PGI2/TXA2 ratio toward vasodilatation. In contrast, the trichlormethiazide treatment, which achieved blood pressure reduction to almost the same extent, significantly decreased PGI2/TXA2 ratio. Vasodilator eicosanoids, e. g. PGI2, PGE2 and PGD2, dose-dependently decreased (3H)-thymidine uptake by vascular smooth muscle cells in culture whereas vasoconstrictor TXA2 enhanced (3H) thymidine uptake in a dose dependent manner. Indeed 2 x 10(-5) M ketanserin significantly decreased (3H) thymidine uptake by vascular smooth muscle cells by 48% although the same dose of methysergide, nonspecific serotonin inhibitor, did not affect the uptake by vascular smooth muscle cells. These results clearly indicate that the blood pressure reduction in ketanserin treatment is uniquely associated with a decrease in vascular thromboxane generation, and that it is possibly beneficial to protect vascular wall against medial hyperplasia of vascular smooth muscle cells, an integral component of arterial sclerotic changes in hypertension.

We investigated the pharmacokinetics of OK-432, au immunomodulator of streptococcus preparation which, is used in cancer patients for active nonspecific immunotherapy. First, OK-432 was labeled with 99mTechnetium in vitro. Four patients with malignancy were studied. By the method of scintigraphy using gamma camera, OK-432 administered intravenously was found to be distributed in the liver, lung and spleen, by the decreasing grade. When OK-432 was administered subcutaneously or intramuscularly in the buttocks, most of the radioactivity of 99mTechnetium remained locally at the injected site. These results suggested that OK-432 given intravenously was effectively phagocytized by cells of reticuloendothelial system (RES). Compared with other routes of administration, the intravenous route of OK-432 administration is thus considered more effective in order to stimulate RES, which is responsible for the first step of immune reaction.

The pH-dependent 13 C chemical shifts indicate an approximately 1:1 ratio of the 3-OH:4-OH tautomeric forms of singly dissociated 3,4-dihydroxyphenylacetic acid. It is found that the 13 C chemical-shift method is an effective technique for determining tautomeric forms from p K values.

There are various kinds of diagnostic examinations in the field of clinical cardiology. In this field, information concerning cardiac structure, dimensions (hypertrophy and dilatation) and cardiac functions are inevitably important. Noninvasive methods are desirable. Except for radiological examinations, electrocardiography and ultrasonic echocardiography are 2 main examinations in cardiology. Holter monitoring is one of the recent topics in clinical electro-cardiology. It is useful for the detection of rest angina or variant angina. Recently "silent myocardial ischemia" has been studied by using this method. This method is also useful for the study of arrhythmia, which is a major cause of sudden death. Quantitative analysis of arrhythmia in the studies of antiarrhythmic drugs can also be done by Holter monitoring. Late potential is also a topic in electro-cardiology. Ultrasonic echocardiography can detect the changes of cardiac structure and function. Doppler echocardiography, developed recently, has made it possible to estimate intracardiac pressure (especially pulmonary arterial pressure) noninvasively. With esophageal echocardiography findings in left atrium, such as thrombus or myxoma in left atrium can be obtained. The most appropriate tool must be selected from the many kinds of diagnostic examinations for efficient clinical diagnosis and therapy.

The high-frequency vibrations of the first heart sound (S1) have been reported to be associated with the closure of atrioventricular valves. However, the genesis of the low-frequency component (LFC) preceding S1 remains controversial. In order to investigate the genesis of the production of this LFC, we recorded phonocardiograms simultaneously with M-mode echocardiograms in 10 healthy subjects and 26 patients with various diseases including mitral valve replacement. The apical phonocardiograms were recorded using a 100 Hz/12 dB high-pass filter and a commercially available acceleration microphone. Patients with rheumatic mitral valve disease and bundle branch block were excluded from this study. The electrocardiograms demonstrated sinus rhythm in 23, atrial fibrillation in nine, complete atrioventricular block in two and atrial flutter in two. The P-R interval in sinus rhythm ranged from 130 to 200 msec. The LFC occurred an average of 24 msec after the QRS complex, but 38 msec before the first high-frequency component of S1. The final fast closing movement of the mitral valve echogram started following the onset of LFC in sinus rhythm or the arrhythmias. Coaptation of the mitral valve leaflets was coincident with the first high-frequency S1. In 23 cases with the visible tricuspid valve, the valve closure occurred 28 msec after that of the mitral valve. The onset of the LFC was almost synchronous in timing with, or very close (10 msec or less) to the initial upstroke of apex cardiograms simultaneously recorded in 10 cases. The amplitude of the LFC was constantly smaller than that of S1 in all cases, but it was variable in atrial fibrillation or complete atrioventricular block. The LFC became loudest after a short RR interval and then ventricular systole was coincided in time with the rapid filling of the left ventricle, or when atrial systole was very close in time to an expected time of ventricular systole. It is certain that antegrade mitral blood flow was decelerated at that time, though the mitral valve was in the rapidly closing process. We conclude that the LFC is produced by the vibration of cardiohemic system, or the acceleration of the left ventricular mass plus the deceleration of blood flow, and that atrial activity and atrioventricular valve tension are not prerequisite to the production of this soft apical vibration preceding S1.

To determine the usefulness of pulsed Doppler echocardiography (PDE) in diagnosing aortic regurgitation (AR), the following two studies were performed. PDE and phonocardiography (PCG) were evaluated for the diagnosis of AR in 36 patients for whom angiography was performed. In 24 patients with grade 2 to 4 by Sellers' classification, all PDE studies were positive for AR (sensitivity of 100%) and PCG studies were positive in 21 patients (sensitivity of 88%). Among 10 patients of grade 1, PDE studies were positive for eight (sensitivity of 80%) and PCG studies were positive for seven (sensitivity of 70%). Angiography was negative for AR in two PCG-proven cases, and PDE also proved AR in one of these. Thus, in all patients, the sensitivity of PDE and PCG were 94 and 82%, respectively. These results indicate that AR may be missed during auscultation, or even when using the latest type PCG. The ability of detecting silent AR was studied in 160 consecutive patients with AR. PDE was positive for AR in 156 of 160 consecutive patients who were diagnosed as having AR by PDE or PCG. In the remaining four patients, three were diagnosed by PCG alone and one by pharmacodynamic phonocardiography using methoxamine (ME-PCG). On the other hand, in 137 of 160, Ar was proven by PCG, and the remaining 23 were so-called "silent AR". ME-PCG was performed for 11 cases of silent AR, but an unequivocal AR murmur was detected in only five. Therefore, the sensitivity of PDE in diagnosing silent AR was 96 percent, while that of ME-PCG was only 45 percent. Thus, compared to PCG and even pharmacodynamic PCG, PDE is a much more sensitive method of diagnosing AR. However, in mild AR cases, angiography, PDE and PCG, all have some limitations in diagnosing AR.

Cardiac involvement of mucopolysaccharidosis has not been well characterized by echocardiography. In this paper, we reported a case of Hunter syndrome with special reference to the noninvasive diagnosis of cardiac anomalies. A 21-year-old male of Hunter syndrome was referred to our noninvasive laboratory for the evaluation of his heart murmurs. He was strikingly dwarfed, 115 cm in height and 28 kg in weight, and had apparently Gargoyle-like facial appearance. Physical examination disclosed a mild funnel chest and a loud systolic murmur. Blood pressure was 98/56 mmHg and regular pulse rate was 100/min. The chest X-ray film revealed a shift of the heart to the left with a prominent pulmonary artery segment. There were no signs of pulmonary congestion. The electrocardiogram demonstrated right axis deviation, clockwise rotation and left atrial overload. In phonocardiograms, a basal ejection and an apical scratchy systolic murmurs were recorded. The latter was associated with a presystolic murmur and a loud first heart sound. A loud pulmonary second heart sound was also present. Outstanding findings were observed in the two-dimensional and M-mode echocardiograms, which showed remarkable thickening of both mitral valve leaflets with reduced opening. There was also generalized thickening of tricuspid and aortic valves, and endocardium of the free ventricular wall. Two leaflets of the tricuspid valve were visualized to prolapse, but the aortic valve motion appeared intact. In addition, echocardiograms revealed the dilatation of right-sided cardiac chambers and pulmonary artery, but the size of the left ventricle was rather small. Pulsed Doppler echocardiography demonstrated systolic turbulence in the right atrium in the vicinity of the tricuspid valve orifice. Stenotic turbulence was also recorded in the inflow tract of the left ventricle during diastole. Thus, the final diagnosis of predominant mitral stenosis associated with tricuspid valve prolapse and pulmonary hypertension was obtained. In conclusion, cardiac involvements in Hunter syndrome were precisely evaluated by noninvasive methods. Hunter syndrome may be considered as one of the etiologies producing mitral stenosis.

A 52-year-old male patient with the Ehlers-Danlos syndrome (familial hypermobility of the joints, hyperextensibility of the skin and atrophic cutaneous scars) was evaluated because of a mitral regurgitant murmur. Echocardiography demonstrated marked mitral valve prolapse of the both leaflets and vegetation-like thickening of the anterior leaflet of the mitral valve. Two-dimensional color flow mapping showed severe mitral regurgitation. This patient had also acrogeria-like facial appearance and very thin skin (subcutaneous veins were readily visible). He developed repeated rupture of radial, ulnar and middle cerebral arteries and expired. A histological section of the ruptured ulnar artery demonstrated no infectious process. In view of the joint hyperextensibility, very thin skin, characteristic facial appearance and the spontaneous occurrence of three successive ruptures of peripheral arteries, a diagnosis of Ehlers-Danlos syndrome (type IV) was made. Although mitral valve prolapse is reportedly common in type I, II and III Ehlers-Danlos syndrome, this report emphasizes that it may also occur in patients with type IV Ehlers-Danlos syndrome and the relevant literatures are reviewed.

A case of recurrent multiple cardiac myxomas was presented. The patient was a 27-year-old housewife. Four years ago, she underwent urgent resection of a left atrial myxoma and replacement of the interatrial septum with a patch graft by right atrial approach. The tumor was very friable and a part of the tumor dropped into cardiac chambers during the operation, and immediately saline lavage and aspiration were performed. The recovery was uneventful. On March, 1981, she was readmitted to our hospital because of increasing dry cough. Two-dimensional echocardiography demonstrated abnormal masses in the right atrium, right ventricle, and left atrium. Open heart surgery revealed three independent tumors, which were successfully removed. All tumors were benign myxomas histologically. The patient returned to full-time housework again. A case of recurrent multiple myxomas has not been previously reported. The recurrence of the myxoma in our case is thought to be caused by implantation of tumor cells during the initial operative procedure. Our case will suggest the malignant potentiality of cardiac myxoma. The necessity of radical excision and gentle handling of the tumor during the operation are reemphasized. Postoperative follow-up study is also mandatory for early detection of the recurrence of this potentially malignant neoplasm.

In 18 open chest canine experiments, the ability of the left ventricle to transmit a mechanical vibratory tone from base to apex has been studied. An artificial tone source of constant amplitude and frequency was applied to the base of the exposed left ventricle. A miniature vibration sensor was applied to the anterior epicardium near the ventricular apex. This permitted us to obtain a heart surface phonocardiogram, in order to detect the portion of the source vibration which was transmitted to the apex. In three of the dogs, the heart surface phonocardiogram from the apex was compared with simultaneous intraventricular phonocardiograms which showed the amplitude of the vibration which reached the intraventricular blood mass. It was found that the normal ventricle transmits the tone from base to apex almost exclusively during systole, when the ventricle is contracted and stiff. In marked contrast, the normally relaxed and soft ventricle fails almost completely to transmit the tone to the apex. In conditions of poor relaxation ability of the left ventricle due to global hypoxemia, manifested by a long "Time Constant T", an abnormal diastolic transmission of the tone to the apex occurred during early diastole. We have defined this abnormal early diastolic "crescendo-decrescendo" type of transmissibility as "Type 1". The Type 1 transmission is related to impaired relaxation of the ventricle and is a manifestation of one or more abnormal ventricular muscle properties, such as myocardial stiffness, viscosity and density. In conditions of left ventricular hemodynamic failure caused by global hypoxemia, a separate abnormal mid-to-late diastolic "crescendo" type of transmissibility was found, and is defined as "Type 2".(ABSTRACT TRUNCATED AT 250 WORDS)

To investigate the potential of a new method for detecting coronary sinus (CS), two-dimensional (2-D) echocardiography was satisfactorily performed on 80 consecutive cases, of which the coronary sinus was detected in 74 by adopting parasternal three-chamber approach. These 74 cases were classified into four groups; 25 normal individuals, 7 patients with atrial septal defect (ASD) but without tricuspid insufficiency (TI), 13 with TI and 29 with other cardiac diseases. We measured diastolic maximum diameter of CS on 2-D echocardiograms. The mean diameter of the CS was significantly increased in ASD (9.0 mm) and TI (12.4 mm) comparing with normal control (6.7 mm). The enlargement of CS seemed to correlate with right-sided volume overload. Although there were three exceptional cases, we could observe the CS during the whole cardiac cycle only in patients with TI. We conclude that CS is excellently detected in over 90% of cases by a new parasternal approach and that the diameter of CS would be a new screening index of right-sided volume overload.

We analyzed the relation of left ventricular size and performance to clinical courses and surgical outcomes using echocardiography. Group A consisted of 19 patients with mitral regurgitation (MR) who presented congestive heart failure of grade III or IV, and group B consisted of 58 patients with MR whose cardiac function was grade I or II. Clinical follow-up spanned one to nine years, with an average of 4.5 years. At the initial examination, the average end-diastolic LV dimension (LVDd) and its index (LVDdI), left atrial dimension (LAD) and its index (LADI) and cardiothoracic ratios (CTR) were significantly greater in group A (LVDd 61.2 +/- 7.1 mm, LVDdI 41.5 +/- 6.9 mm/m2, LAD 51.4 +/- 8.4 mm, LADI 35.4 +/- 11.1 mm/m2, CTR 63.4 +/- 8.6%) than in group B (LVDd 52.0 +/- 7.9 mm, LVDdI 35.0 +/- 6.4 mm/m2, LAD 37.2 +/- 9.6 mm, LADI 25.4 +/- 6.5 mm/m2, CTR 48.9 +/- 4.4) (p less than 0.001). The LVDd and LAD were less in mitral valve prolapse than in rheumatic MR or MR due to flail mitral valves. In rheumatic MR, congestive heart failure did not become prominent until the left ventricle and atrium were markedly enlarged. In group A, patients whose LVSVI were over 40 ml/m2 and LAD were over 50 mm took clinical downhill courses under medical treatment and were referred for surgery. The risk of death (medically or surgically) was higher in patients whose LAD, LVSVI or CTR was markedly increased (LAD greater than 70 mm, LVSVI greater than 60 ml/m2 or CTR greater than 70%). The rates of change in LAD and LVDd were 1.6 and 0.9 mm/year in group B, but they became accelerated after the onset of congestive heart failure, and were 2.6 and 6.4 mm/year in group A. In surgical cases, the LVDd returned to the normal range postoperatively, but their LAD remained in the abnormal range in all but one case. We concluded that echocardiography is an indispensable method for a follow-up study of MR and that it may be helpful in predicting individual clinical courses and surgical effects.