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Biomedical subjects

K Tsunoda

Publications and source records attributed to K Tsunoda.

At least 109 records · Page 6Linked to original sources

[Three-phase bone scintigraphy of Kienböck disease].

Thirty-three joints in 31 patients of Kienböck disease were evaluated with three-phase bone scintigraphy. Follow-up studies were performed in 19 cases of them. The patients with increased ulnar blood flow on arterial phase and ample perfusion on venous phase in angiograms showed good clinical prognosis. This ample ulnar blood flow and perfusion might be essential for the recovery of this disease. Although staging was possible using static images alone, blood pool images provided more information about the present condition of lesions, such as hyperemic state and remodeling reactions. Blood pool image was indispensable for staging and analyzing lesions and evaluating post-operative course. Increased lunate perfusion in venous phase of angiograms and localized lunate uptake in blood pool images were the favorable signs, which were shown in most cases with good prognosis. It is concluded that three-phase bone scintigraphy gives useful informations for evaluating Kienböck disease which can not be obtained by conventional bone scintigraphy.

Adult↗

Maternal and umbilical venous levels of endothelin in women with pre-eclampsia.

Endothelin is a recently discovered, potent vasoconstrictive peptide. To investigate its involvement in pre-eclampsia, we measured its concentration in the plasma of 10 healthy non-pregnant women, 19 healthy pregnant women in early pregnancy, 26 healthy pregnant women in the third trimester, 18 women with pre-eclampsia in the third trimester and 6 women with pre-eclampsia in the postpartum period. In addition, the concentration of endothelin in umbilical venous plasma was measured in 7 healthy pregnant women and in 4 with pre-eclampsia. A sandwich-enzyme immunoassay for endothelin-1[1-21] was used. The plasma concentration of endothelin in pre-eclampsia significantly exceeded that of the healthy pregnant women during the third trimester. In pre-eclampsia this elevated level of plasma endothelin normalised with the fall in blood pressure 7 days postpartum. The level of endothelin in the umbilical vein was 6 to 8 times higher than that in the cubital vein both in the healthy pregnant women and in those with pre-eclampsia, but there was no significant difference in the umbilical venous plasma concentration of endothelin between those two groups. These observations suggest that the synthesis of endothelin may be increased in pre-eclampsia and that this increase may play a role in the elevation of peripheral vascular resistance and the production of peripheral ischaemic damage. Damage to the endothelial cells may then stimulate the synthesis of endothelin to initiate a vicious cycle.

Adult↗

[Antihypertensive effect of a non-peptide angiotensin II receptor antagonist, MK954, in patients with essential hypertension].

We examined the chronic effects of MK954, a novel orally active angiotensin II receptor antagonist, on blood pressure and renal function in 8 patients with essential hypertension for 2-4 weeks. All patients, four men and four women, 48.0 +/- 15.3 year-old (mean +/- SD), were hospitalized and given normal sodium diet (NaCl 10 g/day). After a control period with placebo for one week, MK954 was administered orally at 8 AM every day. The initial dose of MK954 was 12.5 mg/day, then the dose was increased up to 100 mg/day until diastolic blood pressure fell below 90 mmHg. The average dose was 59.4 +/- 43.7 mg/day. Casual blood pressure in supine position decreased significantly from 161.0 +/- 6.6/95.0 +/- 3.5 mmHg to 145.8 +/- 8.1/83.3 +/- 3.7 mmHg without any change in pulse rate. Non-invasive ambulatory blood pressure monitoring revealed that once daily administration of MK954 lowered blood pressure for 24 hours but did not affect circadian rhythm or variability of blood pressure. Reduction of blood pressure was slightly greater during day time than during sleeping time. Unlike a peptide angiotensin II antagonist, there was no pressor action of MK954 as agonist. No significant alternations were observed in body weight, serum electrolytes, creatinine clearance, urine volume or urinary excretion of sodium. Plasma renin activity (PRA) rised significantly after MK954 treatment but plasma aldosterone concentration (PAC) did not change. The reasons why PAC was not reduced are unclear. The doses of MK954 employed in this study might be insufficient to inhibit adrenal angiotensin II receptor. In conclusion, MK954 has long acting hypotensive effect in essential hypertension without affecting renal function.

Adult↗

Evaluation of alkalinized lidocaine solution in brachial plexus blockade.

The effect of alkalinization of lidocaine solution in brachial plexus blockade was evaluated in a double blind study. Commercial 1.5% lidocaine with epinephrine 1 : 200,000 (pH 5.72) was compared with an alkalinized solution of lidocaine (pH 7.12). 10 mg.kg(-1) of each solution was administrated by the axillary perivascular technique in 34 adult patients scheduled for elective surgery. The onset and spread of sensory blockade and the intensity of motor blockade were determined. An alkalinized lidocaine solution produced more complete sensory blockade in all of four main nerves of the upper extremity as compared with the control lidocaine solution. The onset of sensory blockade in the musculocutaneous, radial, ulnar and median nerves was shortened 58%, 40%, 30% and 28%, respectively, by employing the alkalinized lidocaine solution. Also the analgesic onset in the radial and musculocutaneous nerves was significantly faster than the other two nerves ( P < 0.05 and P < 0.01). Furthermore, the intensity of motor blockade was greatly potentiated when alkalinized lidocaine solution was employed. There was no significant increase in plasma concentration of lidocaine in patients who were given alkalinized solution.

Clinical Trial↗

Chronic synergistic effect of endothelin-1 and angiotensin II on blood pressure in conscious rats.

We assessed whether there is an interaction between angiotensin II (Ang II) and endothelin-1 (ET-1) in the regulation of blood pressure and sodium and water metabolism in rats. Male Sprague-Dawley rats were divided into four groups. Group I rats received Ang II at a subpressor dose (400 micrograms/kg/day i.p.) for up to 6 days. Group II rats received ET-1 at a subpressor dose (3 micrograms/kg/day i.v.) for up to 6 days. Group III rats received both the subpressor dose of Ang II and the subpressor dose of ET-1. Group IV rats received vehicle only. There was no significant difference in systolic blood pressure (SBP) among groups I, II, and IV during the study. On day 6, SBP in groups I, II, and IV was 148.0 +/- 3.0, 142.7 +/- 2.9, and 143.5 +/- 3.0 mm Hg, respectively. On the other hand, SBP in group III was higher than those of the other groups on day 2 and remained elevated thereafter. On day 6, SBP in group III rats was 189.0 +/- 12.5 mm Hg. There were no significant differences in body weight, fluid intake, urine volume, urinary sodium excretion, or urinary potassium excretion among the four groups. The present results suggest that Ang II and ET-1 exert their pressor effects synergistically and might play a role in controlling blood pressure. They also suggest the possibility of the existence of a common pathway in the hypertension-producing mechanism of these two peptides.

Angiotensin II↗

Antihypertensive effect of captopril and enalapril in endothelin-infused rats.

Comparative effects of angiotensin converting enzyme inhibitors and calcium channel blockers were assessed in rats infused chronically with synthetic endothelin. When 50 mg/kg/day of captopril orally or 6 mg/kg/day of enalapril intraperitoneally was administered simultaneously with 60 micrograms/kg/day of endothelin, the systolic blood pressure was on Day 1 142.7 +/- 5.9 mmHg (p less than 0.05) or 128.7 +/- 6.7 mmHg (p less than 0.05), respectively, compared to the rise to 163.8 +/- 4.7 mmHg when endothelin alone was infused. The antihypertensive effect of captopril or enalapril was sustained for the entire experimental period and was not associated with a significant change in urinary sodium excretion, whereas both drugs induced a significant increase in urine volume. Chronic infusion of angiotensin II intraperitoneally at a subpressor dose (400 micrograms/kg/day) reversed the antihypertensive effect of captopril in endothelin-infused rats. When 6 mg/kg/day of benidipine or 10 mg/kg/day of nilvadipine orally was administered simultaneously with 60 micrograms/kg/day of endothelin, the systolic blood pressure was on Day 1 137.0 +/- 2.4 mmHg (p less than 0.05) or 119.7 +/- 5.9 mmHg (p less than 0.05), respectively, compared to the rise when endothelin alone was infused. The antihypertensive effect of benidipine or nilvadipine was sustained for the entire experimental period and was not associated with any significant changes in urine volume and urinary sodium excretion. These results indicate that the reduced sensitivity of the peripheral arteries to endothelin may be involved in the mechanism of the hypotensive action of angiotensin converting enzyme inhibitors, dependent on the suppressed angiotensin II formation.

Animals↗

[The treatment of hypertensive patients with renal insufficiency--a comparison of the blood pressure management in patients with diabetic nephropathy and patients with hypertensive nephropathy].

It is well known that hypertension (HT) is frequently accompanied with diabetic nephropathy (DN) and that HT contributes to progression of DN. Thus, proper anti-hypertensive therapy is required in hypertensive patients with DN. However, there is so far no consensus of optimal blood pressure (BP) level to maintain the renal function in these patients. In order to evaluate the optimal BP level in the patients with renal insufficiency, we investigated the relation between BP and renal function in 15 DN patients with HT (aged 56.9 +/- 11.7 years at the first medical examination; 6 male and 9 female, total 117 patient-years) and 20 patients with hypertensive nephropathy (aged 44.3 +/- 13.0 years at the first medical examination; 17 male and 3 female, total 207.5 patient-years) as the control, who receive antihypertensive therapy for more than 4 years as outpatients at the second department of internal medicine of Tohoku University Hospital between 1974 and 1990. During this period 7 patients with DN came to receive hemodialysis therapy 2 to 6 (average 3.8 +/- 1.3) years after the first medical examination. As a result, in patients with hypertensive nephropathy, there was a tendency to show that the lower the mean BP was, the better the renal function. On the contrary, in DN patients there was an optimal mean BP (MBP) range; i.e, when MBP was controlled in this range, the deterioration rate of renal function was delayed, while deviation of MBP from this range made the renal function worse (p less than 0.01). However, this range varied with the serum creatinine (SCr) concentration level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Radial wedge osteotomy for Kienböck disease.

A radial wedge osteotomy, with reduction of the inclination angle of the distal part of the radius, was performed in twenty-seven patients who had Kienböck disease. After two to five years of follow-up, all of the patients were free of pain or had only mild pain in the wrist with strenuous activity. Flexion-extension of the wrist improved by more than 10 degrees in about half of the patients, and in most of the patients the grip strength increased by five kilograms or more. All but two of the postoperative results were satisfactory, as evaluated by the criteria of Lichtman et al. The osteotomy was effective even in patients who had zero or positive ulnar variance.

Adolescent↗

[The effect of blood pressure control on the progression of chronic glomerulonephritis associated with hypertension].

It is well known that hypertension (HT) frequently develops in patients with chronic glomerulonephritis (CGN) and that HT contributes to progression of CGN. So, proper antihypertensive therapy is required in hypertensive patients with CGN. However, there is so far no consensus of optimal blood pressure (BP) level to maintain the renal function in these patients. In order to evaluate the BP control level in the patients with renal insufficiency, we investigated the transition of BP and renal function in 22 CGN patients with HT (average age 36.5 +/- 9.9 years at the first medical examination, 15 male, 7 female, total 179.5 patient-years), who receive antihypertensive therapy for more than 5 years as outpatients at the second department of internal medicine of Tohoku University Hospital between 1975 and 1990. Renal biopsy had been performed in all these patients for CGN diagnosis. During this period 7 patients came to receive hemodialysis therapy from 5 to 10 (average 7.6 +/- 2.1) years after the first medical examination. In one of these 7 patients, the rate of decline in renal function accelerated after child-birth, and one after two years interruption of treatment. The other 13 patients are currently receiving drug treatments at our hospital. As a result, in CGN patients there was an optimal mean BP (MBP) control range, that is, when MBP was controlled in this range, the rate of decline in renal function became slow, but when MBP deviated from this range it became fast (p less than 0.01). Moreover, this range changed according to the serum creatinine (SCr) concentration level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Responsiveness of cultured papillary collecting tubules to vasoactive hormones: comparison between spontaneously hypertensive rats and Wistar-Kyoto rats].

To investigate whether altered renal medullary prostaglandin (PG) synthesis is involved in the development of hypertension in spontaneously hypertensive rats (SHR), we compared the hormonal responsiveness of cultured renal papillary collecting tubule (RPCT) cells from SHR and Wistar-Kyoto rats (WKY) as control. Basal levels of PGE2 and cAMP were lower in 4-weeks-old SHR than in WKY, while PGE2 synthesis after stimulation with arachidonate, A23187 or bradykinin and the level of cAMP responded to vasopressin or exogenous PGE2 were similar in both strains. There was no difference in basal nor stimulated levels of cGMP between both strains. In 16-week-old rats, basal levels of cAMP, cGMP and PGE2 were significantly lower than in 4-week-old rats, but no differences were recognized between both strains. These results suggest that RPCT cells of SHR and WKY at the post-weaning period may differ in the metabolism of PGE2 and cAMP. This difference may be attributed to the possible defect in arachidonate availability in SHR.

Animals↗

Chronic effects of synthetic endothelin on blood pressure and sodium excretion in rats.

Continuous infusion of endothelin at a rate of 60 micrograms/kg/day into the jugular vein of rats via osmotic minipumps induced a significant increase in systolic blood pressure, but did not induce any significant changes in urine volume and urinary sodium excretion, compared to those in vehicle-infused rats. When 6 mg/kg/day of benidipine, a newly developed calcium channel blocker, was administered simultaneously with 60 micrograms/kg/day of endothelin, the systolic blood pressure of conscious rats rose on Day 1 to only 137.0 +/- 2.4 mm Hg (P less than .05) compared to the rise to 163.8 +/- 4.7 mm Hg when endothelin alone was infused. The antihypertensive effect of benidipine was sustained. The present results suggest that endothelin can act as a circulating hormone. In addition, they clearly demonstrate that the calcium channel blocker attenuates the elevation of blood pressure induced by endothelin.

Animals↗

Role of bradykinin in the regulation of blood pressure and renal blood flow in DOCA-salt hypertensive rats.

We examined the role of bradykinin in the onset and/or the maintenance of blood pressure and renal blood flow in deoxycorticosterone acetate (DOCA)-salt hypertensive rats by using a competitive antagonist of bradykinin [Arg-Pro-Hyp-Gly-Thi-Ser-Dphe-Thi-Arg; Hyp, L-4-hydroxyproline; Thi, beta-(2-theinyl-L-alanine)]. The intravenous injection of the bradykinin antagonist (25, 50 and 100 micrograms) produced an increase in mean arterial pressure in all rats treated with tap water, 1% NaCl and DOCA + 1% NaCl. However, the magnitude of the increase in mean arterial pressure was significantly lower in the DOCA-hypertensive rats than in the two groups of rats drinking tap water and 1% NaCl after 4 and 6 weeks, but there was no significant difference after 2 weeks. The bradykinin antagonist induced a decrease in renal blood flow in all rats. However, the extent of the fall in renal blood flow was reduced in the DOCA-hypertensive rats compared with the control rats drinking tap water. These results suggest that endogenous bradykinin is depressed in the established phase of hypertension in DOCA-hypertensive rats. It is also suggested that endogenous bradykinin may counteract the elevation of vascular resistance in the early stages of this model.

Animals↗

Calcium channel blockers reverse the sustained elevation of blood pressure induced by chronic infusion of endothelin in conscious rats.

To determine whether endothelin could act as a circulating hormone in the regulation of blood pressure and sodium-water excretion, we assessed the chronic effects of synthetic endothelin on systolic blood pressure, urine volume and urinary sodium excretion in conscious rats, and also evaluated the effects of benidipine or nilvadipine, newly developed calcium channel blockers, in rats infused chronically with synthetic endothelin. Continuous infusion of endothelin at a rate of 60 micrograms/kg/day into the jugular vein via osmotic minipumps induced a significant increase in systolic blood pressure, but did not induce any significant changes in urine volume and urinary sodium excretion, compared to those in vehicle-infused rats. On the contrary, the infusion of endothelin at a rate of 6 micrograms/kg/day did not induce any significant changes in systolic blood pressure, urine volume and urinary sodium excretion, compared to those in vehicle-infused rats. When 6 mg/kg/day of benidipine or 10 mg/kg/day of nilvadipine was administered simultaneously with 60 micrograms/kg/day of endothelin, the systolic blood pressure rose on Day I to only 137.0 +/- 2.4 mmHg (p less than 0.05) and 119.7 +/- 5.9 mmHg (p less than 0.05) compared to the rise to 163.8 +/- 4.7 mmHg when endothelin alone was infused. The antihypertensive effect of benidipine or nilvadipine was sustained for the entire experimental period and was not associated with any significant changes in urine volume and urinary sodium excretion. The present results suggest that endothelin can act as a circulating hormone and might be involved in the regulation of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of intracerebroventricular administration of adrenoceptor-agonists on the regulation of renal water and electrolytes handling through endocrine, renal and hemodynamic function.

In order to assess the roles of central adrenoceptors in the release of atrial natriuretic peptide (ANP), aldosterone (ALD), vasopressin (AVP) and renin as well as in the regulation of renal and cardiovascular functions, either norepinephrine (NE; 0.07 microgram/kg/min), guanabenz (GB; alpha 2-agonist; 0.4 microgram/kg/min), methoxamine (MET; alpha 1-agonist; 0.4 microgram/kg/min), or isoproterenol (ISO; beta-agonist; 0.07 microgram/kg/min), dissolved in the artificial cerebrospinal fluid (ACSF), was intracerebroventricularly (i.c.v.) administered at a rate of 10 microliters/min for 30 min in anesthetized dogs. In the control study, the drugs were omitted. NE decreased mean arterial pressure (MAP), urinary osmolality (Uosm) and plasma ALD and AVP concentrations, and increased urine flow (UF). GB increased UF and urinary K excretion without any changes in urinary Na excretion, but decreased plasma ALD and AVP, heart rate, and Uosm without changes in MAP. ISO decreased MAP and plasma ALD, and increased Na and K output, renal plasma flow and UF with decreased Uosm. MET and ACSF failed to affect any of these parameters. Glomerular filtration rate, plasma ANP concentration and renin activity did not change in any of the studies. The present results suggest that central alpha 2- and beta-adrenoceptors may attenuate ALD and/or AVP release without changes in ANP and renin release, and decrease blood pressure, thereby causing a diuresis and natriuresis.

Adrenergic alpha-Agonists↗

Interaction of endothelin and Ca++ entry blockers on renal circulation in anesthetized rabbits.

We examined an interaction of endothelium-derived vasoconstrictor endothelin and Ca++ entry blockers on renal blood flow in anesthetized rabbits. A bolus intrarenal arterial injection of endothelin at doses of 10, 25 and 50 ng produced a decrease in renal blood flow with a dose-dependent fashion, while there was no change in systemic arterial pressure. A similar extent of the decrease in renal blood flow was produced at doses of endothelin 50 ng(2.0 x 10(-11)M), angiotensin II 10 ng (9.7 x 10(-12)M) and norepinephrine 250 ng (1.5 x 10(-9)M), although the decrease in renal blood flow by endothelin was sustained in contrast to angiotensin II or norepinephrine. Pretreatment with Ca++ entry blocker nifedipine (1.0 microgram/kg/min) or diltiazem (20 micrograms/kg/min) attenuated the decrease in renal blood flow and reduced the duration time. These results suggest that exogenous endothelin produces a renal vasoconstriction in vivo. However, it seems that endothelin is less potent than angiotensin II in renal circulation in anesthetized rabbits. It is also indicated that the decrease in renal blood flow by endothelin could be mediated through a common Ca++ channel pathway in renal vasculatures.

Anesthesia↗