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Biomedical subjects

T Sakamaki

Publications and source records attributed to T Sakamaki.

At least 91 records · Page 5Linked to original sources

[Anthracycline cardiotoxicity evaluated by digitized M-mode echocardiography].

Ten patients with malignant diseases whose mean age was 20.0 +/- 13.2 years received anthracycline derivatives therapy and were evaluated for their left ventricular systolic and diastolic functions by computer-assisted digitized M-mode echocardiography. Fractional shortening (%FS), a parameter of systolic function, was measured. The first derivative of left ventricular dimension change (peak LV dD/dt), posterior wall thinning (peak LVPW thinning rate) and interventricular septum thinning (peak IVS thinning rate) were used as indices of diastolic function. Blood pressure (BP) was measured noninvasively at the end of the echocardiographic examination and hemoglobin concentration (Hb) was measured on the same day. These examinations were performed immediately before administration of anthracycline and one week and one month after the last administration. Statistical analyses were performed using the Student's t-test. The mean BP, HR, LVDd, LVDs, LVPW and IVS remained unchanged following the drug administration. %FS did not change significantly; 36.8 +/- 6.3%, before the administration, 35.3 +/- 6.5%, one week after the administration, and 36.5 +/- 5.1%, one month after the administration. Peak LVdD/dt and the peak LVPW thinning rate decreased appreciably from 4.46 +/- 1.10 to 3.76 +/- 1.08, and from 7.99 +/- 1.55 to 6.41 +/- 1.04, respectively, one week after the administration. The peak IVS thinning rate decreased from 3.54 +/- 0.81 to 2.99 +/- 0.79 after one week (p < 0.01). All of these values returned to the control levels in one month after the drug administration. We concluded that the indices of left ventricular diastolic function were more sensitive for detecting cardiac impairment than those of systolic function during the course of anthracycline therapy.

Adolescent↗

Transient osteopenia of the hip joint in children.

Two pediatric cases of transient osteopenia of the hip joint are reported. Roentgenograms showed bone atrophy in the femoral head, the femoral neck, and the pelvis. Bone scintigrams showed a higher accumulation. At the follow-up study, osteopenia disappeared in both cases, however coxa magna was recognized in one case. The emphasis is on differential diagnosis from more severe disease, because the syndrome is characterized by spontaneous resolution.

Bone Diseases, Metabolic↗

[Clinical studies on 3 pairs of monozygotic twin sisters affected by Graves' disease].

Clinical studies were undertaken of three pairs of monozygotic twin sisters affected by Graves' disease. The evidence that the twins were monozygotic was established by similarity in physical appearance, identical blood-group antigens and identical HLA types. All pairs were female, and the evidence of Graves' disease in both members of the pair was observed in 2 out of 3 pairs. In the remaining pair the disease started in the elder sister, but the younger sister still remained in euthyroidism in spite of the presence of diffuse goiter. The disease occurred in the second decade in all the patients, and the interval between the occurrence of the disease in twin sisters was 1 to 4 years. No common specific type of HLA was found among all three pairs, but DR4 was common in two pairs of twin sisters showing positive MCHA test. Serum TRAb was positive in 2 pairs of twin sisters but negative in the remaining one. However, it became positive in the elder sister of the latter pair during the antithyroid treatment. The effect of antithyroid drug treatment was found to be similar in each of the twin sisters, and the serum TRAb moved almost in parallel with serum FT4 level. These results indicate that a genetic factor may be of great importance in the aetiology of Graves' disease, and there was a strong preponderance for it to occur in women and the second decade was the peak age for its occurrence. The common specific type of HLA for all Graves' patients was not found in this study. A strong relationship was observed between Grave's disease and TRAb.

Adult↗

A new class of HIV-1-specific 6-substituted acyclouridine derivatives: synthesis and anti-HIV-1 activity of 5- or 6-substituted analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT).

A series of novel acyclouridine derivatives substituted at both the C-5 and C-6 positions were synthesized for the purpose of improving the activity of a recently reported HIV-1-specific lead, 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT). Preparation of C-6 substituted derivatives was carried out based on the following three methods: (1) LDA (lithium diisopropylamide) lithiation of a thymine derivative (4) and subsequent reaction with electrophiles, (2) an addition-elimination reaction of HEPT or its 6-(phenylsulfinyl) derivative (10), or (3) palladium-catalyzed cross-coupling between a 6-iodo derivative (16) and terminal alkynes. Following the methods, 21 C-6 substituted analogues were synthesized. Among these, 6-(cyclohexylthio) (8), 6-phenoxy (13), and 6-benzyl (27) derivatives showed anti-HIV-1 (HTLV-IIIB) activity with EC50 values of 8.2, 85, and 23 microM, respectively. Preparation of C-5 substituted derivatives was based on either LTMP (lithium 2,2,6,6-tetramethylpiperidide) lithiation of 6-(phenylthio)uracil derivative 37 or the above mentioned palladium-catalyzed cross-coupling of a 5-iodo-6-(phenylthio)uracil derivative (38). Following these methods, 11 C-5 substituted analogues were synthesized. Some 5-substituted derivatives (5-I, 44; 5-CH = CPh2, 49; 5-CH = CHPh (Z), 54; and 5-CH = CH2, 55) were more active than HEPT, but their selectivity indices (SI = CC50/EC50) were lower than that of HEPT. Compound 8 was also evaluated against another HIV-1 strain (HTLV-IIIRF) and HIV-2 strains (LAV-2ROD and LAV-2EHO). Only HTLV-IIIRF was as sensitive as HTLV-IIIB.

Antiviral Agents↗

Effect of saline infusion on urinary calcium excretion in essential hypertension.

Urinary excretion of sodium and calcium was examined in hypertensive (n = 8) and normotensive (n = 7) subjects following infusion of 2% saline at a rate of 11 mL/min for 90 min. The urinary sodium excretion was 204 +/- 38 (mean +/- SEM) muEq/min in normotensives and 233 +/- 28 muEq/min in hypertensives before infusion of saline and increased maximally to 499 +/- 114 muEq/min (P less than .05) and to 928 +/- 68 muEq/min (P less than .01), respectively, after saline infusion. In normotensives, urinary calcium excretion did not change significantly; however, in hypertensives excretion increased markedly (P less than .01) from 6.1 +/- 0.7 muEq/min to 12.3 +/- 1.6 muEq/min. Plasma atrial natriuretic peptide (ANP) levels increased significantly (P less than .05) in both groups. Serum ionized calcium and plasma parathyroid hormone (PTH) levels did not change significantly. The increments of urinary sodium and calcium and of plasma ANP, as well as the preinfusion plasma PTH level, were significantly (P less than .05) higher in hypertensives than in normotensives. The present study showed that exaggerated natriuresis was accompanied by hypercalcinuria and an enhanced rise in plasma ANP in hypertensives. Basal levels of plasma PTH were elevated in hypertensives. The calcium deficiency may be attributable to a close relationship between urinary sodium and calcium, and causally related to the disturbance of sodium and volume homeostasis in hypertension, which results in exaggerated natriuresis.

Adult↗

Time-related changes in plasma adrenal steroids during treatment with spironolactone in primary aldosteronism.

Time-related changes in plasma levels of aldosterone, deoxycorticosterone, corticosterone, and cortisol were studied during treatment with spironolactone in 8 patients with primary aldosteronism due to adenomas. Plasma renin activity (PRA), serum sodium and serum potassium were also measured. The patients were treated with spironolactone, 75 to 225 mg daily, and blood samples were withdrawn on days 7, 14, and 21 to 28 of drug administration. Plasma aldosterone concentrations (PAC) were not altered by spironolactone; however, significant increases were observed in plasma deoxycorticosterone on days 21 to 28 and in plasma corticosterone and cortisol on days 14 and 21 to 28. The suppressed PRA values were markedly increased on days 21 to 28 and low levels of serum potassium returned to the normal range on day 7. The lack of increase in PAC, despite a remarkable rise in PRA and serum potassium, suggests biosynthetic inhibition of spironolactone at the sites of 18-hydroxylation and/or 18-oxidation, because of the elevation of deoxycorticosterone and corticosterone.

Adenoma↗

Clinical application of echocardiographic imaging to diagnosis of coronary artery disease.

Ergometer two-dimensional echocardiography was performed in 28 subjects complaining of chest pain but without myocardial infarction. Sequential ergometer loading was initiated at 50 or 75 watts, and increased in several stages. Apical four-chamber view two-dimensional echocardiograms were recorded onto video tape, and video images were converted into digital computer signals. After cine-loop display, computer image processing included noise reduction and edge enhancement, M-mode measurements were made at a designated level on the two-dimensional echo images. Wall motion was also analyzed directly from the two-dimensional echo images, using an auto-edge detection method. The derived data were compared with results from coronary angiograms. No echo abnormality was observed at rest, whereas during exercise wall motion was depressed at the diseased site of the angiogram; the amplitude of excursion and the changes in systolic and diastolic velocity were disturbed at the septum in LAD-involved patients, and in the posterolateral wall in both Cx and RCA patients. The imaging success rate using the computer-aided analysis was found to be 92.9%. Sensitivity for diagnosis of coronary artery disease was 82.1% and specificity 89.3%. Ergometer two-dimensional echocardiography with assisted computer image processing appears to be one of the most valuable tools for clinical real time evaluation of coronary artery disease.

Coronary Disease↗

Effects of insulin on plasma renin activity, plasma atrial natriuretic peptide and body fluid volume in diabetes mellitus.

The effects of insulin treatment on plasma renin activity (PRA), plasma atrial natriuretic peptide (ANP) and body fluid volume were studied in 16 hospitalized patients with insulin-independent diabetes mellitus. Parameters were recorded for 2 days during treatment by diet alone and for 3 weeks after starting insulin. Blood samples were obtained weekly from 9 patients for the measurement of fasting plasma glucose, hematocrit, PRA and plasma ANP. A 24-hr urine sample was collected to determine the urinary excretion of glucose and sodium. In a separate group of 7 patients, plasma volume and extracellular fluid volume were determined by the Evans blue and sodium thiocyanate dilution tests, respectively. In the group of 9 diabetic patients, significant (p less than 0.05) reductions in fasting plasma glucose, hematocrit and the urinary excretion of sodium and glucose were seen with insulin treatment. PRA fell significantly (p less than 0.05) from 5.2 +/- 1.2 ng/ml/hr (mean +/- SEM) on the control days to 2.3 +/- 0.5 on the 21st day after starting treatment. Plasma levels of ANP averaged 35 +/- 5 pg/ml on the control days and these did not change significantly. In the other group of 7 patients, both plasma volume and extracellular fluid volume increased significantly (p less than 0.05) with insulin treatment. A sodium-retaining effect of insulin and a decrease in osmotic diuresis may have increased the body fluid volume and caused the fall in PRA. Thus, a vasodilatory action of insulin may assist in compensation for the increase in body fluid volume, preventing a rise in plasma ANP levels.

Atrial Natriuretic Factor↗

Increase in hematocrit by nifedipine in hypertensive patients.

The hematocrit, hemoglobin, serum total protein and serum albumin concentration increased significantly following sublingual administration of nifedipine in patients with essential hypertension (p less than 0.05). The mean increase in hematocrit at 60 min after administration was 1.5%. The results suggest a decrease in plasma volume, perhaps due to diuresis and a shift of fluid from the intravascular to the extravascular space.

Adult↗

[Ischemic heart disease evaluated using dipyridamole-stress two-dimensional echocardiography].

Dipyridamole-stress two-dimensional echocardiography (2DE) was performed in 25 subjects, 14 with stenotic and 11 with normal coronary arteries by coronary angiography, to assess the sites and severity of coronary artery stenosis noninvasively. Dipyridamole was administered intravenously with a dose of 0.56 mg/kg for 4 min. 2DE was recorded at the lower papillary muscle level and the percent fractional area change (% FAC) of the left ventricular segments was computed (FV). In all cases with an echocardiographic regional wall motion abnormality in the interventricular septum, a significant stenosis (greater than or equal to 75%) was documented angiographically in the left anterior descending coronary artery (LAD). In seven of eight patients with a segmental abnormality in the inferolateral wall, a significant stenosis was observed in the left circumflex coronary artery (Cx). The sensitivity and specificity of dipyridamole-stress echocardiography were 100% and 92%, respectively, for an LAD stenosis, and and 87.5% and 71%, respectively, for a Cx stenosis. The segmental wall motion abnormality induced by dipyridamole resolved within four to five min after terminating the infusion in patients with coronary artery narrowing of 75%; whereas, it persisted up to six to seven min in patients with 90% narrowing. There was no improvement in the LV wall motion 15 min after the termination of the infusion in patients with severe narrowing (99%). In conclusion, dipyridamole-stress echocardiography proved to be one of the most useful methods, not only for detecting coronary artery disease, but for predicting the severity and for localizing the sites of lesions as well.

Analysis of Variance↗

Complications of Pemberton's pericapsular osteotomy. A report of two cases.

Pemberton's pericapsular osteotomy has been performed since 1970 at the authors' institution on 56 hips in 49 patients. Two complications, obturator dislocation and osteonecrosis of the femoral head, occurred. A ten-year-old girl had an obturator dislocation that was recognized six weeks postoperatively. This dislocation probably occurred because the reduction of the acetabular dysplasia and the varus osteotomy were excessive in degree. Osteonecrosis of the femoral head was recognized in a 13-year-old girl six weeks postoperatively. This complication probably occurred because too much pressure was imposed on the femoral head, which had been dislocated for a long time and whose circumstances changed suddenly.

Adolescent↗

[Clinicopathological study of miliary tuberculosis in patients with hematologic disease].

Seven cases of miliary tuberculosis in patients with hematologic disease were analyzed clinicopathologically. Mean age of the patients was 65 years, and the hematologic diseases were CML, AML, ALL, MDS and malignant lymphoma. Diabetes mellitus was present as a complication in three patients. Miliary tuberculosis was found in 5 cases during the first admission to our hospital owing to hematologic problems. In 4 of 6 cases, fever had started more than two months before admission, consequently, the tuberculosis probably began about that time. After admission, chemotherapy was administered in 5 cases, and steroid in 6 cases for hematologic disease. The mean total quantity of steroid administered was 2,134 mg of prednisolone and average treatment duration was 69 days. The chest roentgenographic shadow was so atypical that miliary tuberculosis was suspected in only one case. The initial chest roentgenogram showed hilar and mediastinal lymph node swelling as well as the shadow of pulmonary tuberculosis in two cases. It was thought that the hilar and mediastinal lymph node swelling could be explained by primary complex, although the patients were of advanced age, or by "secondary complex" reported by Terplan, K in 1940. The diagnosis of tuberculosis was made in two patients before their death by smear of aspirated fluid of cervical lymph node and by bone marrow cell block in one patients, and by pathological examination of mediastinal lymph node biopsy in the other patients. Tubercles were found from bone marrow cell block in 2 out of 5 patients and from bone marrow biopsy in 1 out of 3 patients, but the positive results were reported in 2 patients following death. Smears of sputum, gastric juice, urine, spinal fluid and pleural effusion were negative in all cases. One patient diagnosed as miliary tuberculosis also had pneumocystis carinii pneumonia. This case was treated with antituberculosis drugs for 20 days without improvement. Another patient diagnosed as miliary tuberculosis improved under treatment with antituberculosis drugs, but died of cytomegalovirus pneumonia. Autopsy in 5 cases revealed non-reactive miliary tuberculosis, and pulmonary hemorrhage probably due to DIC was present as a complication in two cases. In these cases, severe immunosuppression, which is a major precipitating factor of miliary tuberculosis, is thought to be induced by hematologic disease itself, chemotherapy, steroid or other underlying disease such as diabetes mellitus. Miliary tuberculosis in such compromised host is cryptic and progresses rapidly. Consequently, early diagnosis is very important. Retrospectively, the unexplained pyrexia was most important to suspect tuberculosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[A noninvasive study on characteristics of the left ventricular function in elderly hypertensive patients].

To characterize the left ventricular (LV) systolic and diastolic function in elderly hypertensives, mechano-and echocardiography was performed in 27 elderly patients more than 65 years of age (20 hypertensives and 7 normotensives) and 46 middle-aged patients (34 hypertensives and 12 normotensives). In normotensives, a positive correlation was found to exist between age and blood pressure, LV wall thickness, II-RF interval and the A/E ratio, whereas the correlation of age to systolic parameters such as ET/PEP and EF was absent. This suggests that the LV diastolic function was impaired progressively by aging with preservation of the LV systolic function. In elderly hypertensives, LV systolic function was deteriorated and the A/E ratio increased as diastolic blood pressure became elevated. The A/E ratio also increased in this group as compared with that in middle-aged hypertensives, although the differences was not statistically significant. Unlike those in middle-aged hypertensives, the indices of LV function except the elevated blood pressure and the increased cardio-thoracic ratio were not significantly different between hypertensive and normotensive elderly patients. This might be because of the wide range of normal values in elderly persons due to the various degrees of atherosclerotic changes and other pathophysiologic factors, which might have masked obvious characteristics of hypertension in elderly hypertensives.

Adult↗

Role of baroreflex in the pressor response of rats with hypertension developed by renal artery stenosis.

We examined the interrelationships between the pressor response to the administration of norepinephrine and arginine vasopressin and baroreflex function in rats with hypertension of two days' duration induced by heminephrectomy and a clip placed on the right renal artery (2-day clipped rats). Mean arterial pressure was higher in the 2-day clipped rats than in heminephrectomized rats without clips (sham-operated rats). The pressor response in the 2-day clipped rats to both agents increased as compared to the sham-operated rats. This hyperresponsiveness was attenuated by administering an angiotensin II antagonist, [1-Sar, 8-Ile] angiotensin II. Baroreflex sensitivity was studied by measuring changes in arterial pressure and pulse interval in response to the injection of phenylephrine. Baroreflex sensitivity was not decreased but markedly increased in the 2-day clipped rats and unaffected by infusing the angiotensin II antagonist. These results provide evidence that 1) in the 2-day clipped rats there are exaggerated pressor responses to vasoconstrictors; 2) the hyperresponsiveness is not causally related to the change of baroreflex sensitivity; and 3) angiotensin II plays a significant role in the increased pressor responses; however, the baroreflex mechanism is not involved in attenuation of the hyperresponsiveness by the angiotensin II antagonist.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Effect of exercise on circulating atrial natriuretic peptide and left ventricular ejection fraction in healthy persons and patients with coronary artery disease.

Radionuclide angiographic measurements of left ventricular ejection fraction were performed at rest and during exercise in 10 normal persons and 11 patients with coronary artery disease. Exercise was continued on a supine bicycle exercise table up to a symptom-limited maximum. Plasma levels of atrial natriuretic peptide (ANP) were also determined at rest and during exercise. Ejection fraction in the normal volunteers was 59 +/- 3% (mean +/- SEM) at rest and increased significantly (p less than 0.01) to 69 +/- 3% during exercise. Ejection fraction in the patients was 47 +/- 5% at rest and did not change significantly during exercise (51 +/- 7%). Plasma ANP in the normals rose significantly (p less than 0.01) from 62 +/- 16 pg/ml at rest to 454 +/- 94 pg/ml during exercise. Plasma ANP in the patients also rose significantly (p less than 0.01) from 231 +/- 102 pg/ml to 794 +/- 170 pg/ml. The response of plasma ANP to exercise was enhanced significantly (p less than 0.05) in the patients as compared with the normals in relation to ejection fraction by analysis of covariance. In both the normals and the patients, plasma ANP was inversely and significantly correlated with ejection fraction during exercise (r = -0.46, p less than 0.05, n = 21), however, not at rest. Because it has been reported that plasma ANP is correlated positively with pulmonary artery wedge pressure, the estimation of plasma ANP during an exercise stress test might be used for the evaluation of cardiac reserve in coronary artery disease.

Adult↗