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T Shiota

Publications and source records attributed to T Shiota.

At least 55 records · Page 3Linked to original sources
PubMed1999

Synthesis and structure-activity relationship of a new series of potent angiotensin II receptor antagonists: pyrazolo[1,5-a]pyrimidine derivatives.

We have already reported 7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid derivatives, which are potent in vitro angiotensin II (AII) antagonists, but have no oral antihypertensive activity. Removal of the carboxylic acid and replacement of the heteroaromatic system afforded potent in vitro antagonists. Removal of the carbonyl oxygen and changing the position of the biphenyltetrazole substituent were critical to the display of oral activity. To improve the in vitro and oral activities, modifications were made of the substituents at the 3- and 5-positions of the pyrazolo[1,5-a]pyrimidine. Structure-activity studies showed the methyl substituent at the 3-position to be essential for potent in vivo activity. We present the design, syntheses, and biological data of a series of pyrazolo[1,5-a]pyrimidine derivatives, which are orally active AII receptor antagonists.

Angiotensin II↗
PubMed1998

Real-time three-dimensional echocardiography for determining right ventricular stroke volume in an animal model of chronic right ventricular volume overload.

BACKGROUND: The lack of a suitable noninvasive method for assessing right ventricular (RV) volume and function has been a major deficiency of two-dimensional (2D) echocardiography. The aim of our animal study was to test a new real-time three-dimensional (3D) echo imaging system for evaluating RV stroke volumes. METHODS AND RESULTS: Three to 6 months before hemodynamic and 3D ultrasonic study, the pulmonary valve was excised from 6 sheep (31 to 59 kg) to induce RV volume overload. At the subsequent session, a total of 14 different steady-state hemodynamic conditions were studied. Electromagnetic (EM) flow probes were used for obtaining aortic and pulmonic flows. A unique phased-array volumetric 3D imaging system developed at the Duke University Center for Emerging Cardiovascular Technology was used for ultrasonic imaging. Real-time volumetric images of the RV were digitally stored, and RV stroke volumes were determined by use of parallel slices of the 3D RV data set and subtraction of end-systolic cavity volumes from end-diastolic cavity volumes. Multiple regression analyses showed a good correlation and agreement between the EM-obtained RV stroke volumes (range, 16 to 42 mL/beat) and those obtained by the new real-time 3D method (r=0.80; mean difference, -2.7+/-6.4 mL/beat). CONCLUSIONS: The real-time 3D system provided good estimation of strictly quantified reference RV stroke volumes, suggesting an important application of this new 3D method.

Animals↗
PubMed1998

Decoy administration of NF-kappaB into the subarachnoid space for cerebral angiopathy.

Subarachnoid hemorrhage (SAH), encephalitis, meningitis, and autoimmune diseases sometimes lead to cerebral angiopathy, characterized specifically by narrowing of vessels, morphological changes in the structure of vessel walls, and a concomitant decrease in cerebral blood flow. Many patients also develop delayed ischemic neurological deficits. Thus, preventing vascular reactions is of paramount importance in treating SAH. Although cerebral vasospasm has some relationship with the inflammatory reaction of major cerebral vessels against the autologous blood, and many trials have attempted to prevent angiopathy after SAH, an effective treatment has not yet been established. The purpose of this article is to evaluate the preventive effect of nuclear factor KB (NF-kappaB) decoy oligo-DNA after SAH; since NF-kappaB is closely related to inflammation. In the rabbit angiopathy model after SAH, we evaluated the effectiveness of the decoy oligo-DNA using the angiographic (digital subtraction angiography) and histological (hematoxylin-eosin and Masson's trichrome staining) methods. Moreover, a gel-shift assay for NF-kappaB was also performed in order to evaluate the activity of NF-kappaB. We describe a new concept for treating cerebral angiopathy after SAH and for successfully inhibiting cerebral vasospasm and morphological changes in vessel walls in a rabbit model. In this treatment, we used synthetic double-strand oligo-DNA with a high affinity for transcription factor NF-kappaB, and cationic liposome complex administered through the cerebrospinal fluid.

Animals↗
PubMed1998

Quantification of aortic regurgitant volume by a newly developed automated cardiac flow measurement method: an in vitro study.

BACKGROUND: Quantifying regurgitant volumes is important for treatment of patients with valvular aortic regurgitation. Simple, reliable methods to quantify aortic regurgitation have been sought both in the catheterization laboratory and the echocardiography laboratory. OBJECTIVES: The aim of our study was to investigate the applicability of a new automated cardiac flow measurement method with color Doppler velocity data for quantifying retrograde flow volumes of aortic regurgitation in an ascending aorta model. METHODS AND RESULTS: A 2-chamber pulsatile flow system with a modeled ascending aorta and a regurgitant aortic valve orifice was developed. The model could generate "aortic regurgitation-like" waveforms through the use of an electrically controlled valve. The regurgitant flows through the orifice (8.5 to 28.1 mL/beat) were measured by an ultrasound flowmeter; they were also calculated in the ascending aorta 1.0 cm above the orifice by the automated cardiac flow measurement method, which integrated spatially distributed digital flow velocity data through "diastole." Calculated regurgitant volumes measured with the low color Doppler filter (5.4 cm/s) agreed well with those measured with the flowmeter (r=.99, P < .001, mean difference=2.2+/-3.7 mL). However, the regurgitant volume was underestimated when 2 higher filter settings were used (9.6 and 10.9 cm/s). Although there was no significant difference in mean volume, higher frame rate (19 frames/s) provided more reproducible results with smaller standard deviation as compared with lower frame rate (7 frames/s). CONCLUSIONS: This new automated cardiac flow measurement method appears to be promising for semiautomatic quantification of aortic regurgitant volume. Appropriate choice of filter setting and high frame rate assists reliable data acquisition.

Aorta↗
PubMed1998

What is the validity of continuous wave Doppler grading of aortic regurgitation severity? A chronic animal model study.

Continuous wave Doppler methods have been widely used clinically for evaluating the severity of aortic regurgitation; however, there have been no studies comparing these continuous wave Doppler methods with a strictly quantifiable reference for regurgitant severity. The purpose of this study was to test the applicability of continuous wave Doppler methods (deceleration slope and pressure half-time) for evaluation of chronic aortic regurgitation in an animal model. Eight sheep were studied 8 to 20 weeks after surgery to create chronic aortic regurgitation. Twenty-nine hemodynamically different states were obtained pharmacologically. A Vingmed 775 system was used for recording continuous wave Doppler traces with a 5 MHz annular array transducer directly placed on the heart near the apex. The aortic regurgitation was quantified as peak and mean regurgitant flow rates, regurgitant stroke volumes and regurgitant fractions determined with pulmonary and aortic electromagnetic flow probes and meters balanced against each other. Peak regurgitant flow rates varied from 1.8 to 13.6 L/min (6.3 +/- 3.2 L/min) (mean +/- SD), mean regurgitant flow rates varied from 0.7 to 4.9 L/min (2.7 +/- 1.3 L/min), regurgitant stroke volume varied from 7.0 to 48.0 ml/beat (26.9 +/- 12.2 ml/beat), and regurgitant fraction varied from 23% to 78% (53% +/- 16%). Only marginal correlations were obtained between reference indexes and continuous wave Doppler deceleration slope and pressure half-time (r = 0.55 to 0.74). A deceleration slope greater than 3 m/sec2 and pressure half-time less than 400 msec did, however, provide 100% specificity for detecting severe AR (regurgitant fraction > 50%). Our study shows that the continuous wave Doppler deceleration slope and pressure half-time methods have limited use for quantifying aortic regurgitation.

Animals↗
PubMed1998

Diagnostic accuracy and role of intraoperative biplane transesophageal echocardiography in pediatric patients with left ventricle outflow tract lesions.

OBJECTIVES: To define the lesion-specific role of biplane transesophageal echocardiography in children with left ventricular outflow tract obstructive lesions, the diagnostic accuracy of transthoracic and transesophageal images were compared, and the impact of transesophageal echocardiography on perioperative management was evaluated. BACKGROUND: The reported high postoperative recurrence of left ventricular outflow tract obstructive lesion can be due to its incomplete surgical relief. A full preoperative definition of the lesions would aid in better surgical outcome. The complexity and spectrum of such lesions provide opportunity to evaluate the role of a recently available biplane transesophageal pediatric probe in its diagnosis and surgical management. METHODS: In 16 consecutive patients (11 male patients) with left ventricular outflow tract obstructive lesions and with a mean age of 7.9 +/- 5.7 years (range 0.25 to 20.0 years) and a mean weight of 29 +/- 19 kg (range 4 to 66 kg), the morphologic and hemodynamic findings of standard preoperative transthoracic and intraoperative biplane transesophageal echocardiography were compared with surgical and cardiac catheterization findings (in seven patients) for the diagnostic accuracy and impact on the surgical management of the lesions. RESULTS: Based on the levels of agreement, transesophageal echocardiography demonstrated higher diagnostic sensitivity (chi-squared analysis = 13.4 < 0.001) to the presence and extent of associated lesions (septal hypertrophy, multiple fibromuscular insertions, involvement of aortic and mitral valves not revealed by transthoracic imaging) and trend toward higher sensitivity (Fisher's exact p = 0.17) to primary morphologic diagnoses (abnormal chordal attachments, prolapsed aortic cusp, and tunnel-like outflow tract obstructive lesions missed by transthoracic imaging). As a result of these factors, intraoperative transesophageal imaging changed the surgical plan in 25% of the patients and modified it in an additional 25% of the patients. CONCLUSIONS: Transesophageal echocardiography can be a reliable diagnostic tool and has an important role in the surgical management of left ventricular outflow tract lesions in children.

Adolescent↗
PubMed1998

Temporal variability of vena contracta and jet areas with color Doppler in aortic regurgitation: a chronic animal model study.

OBJECTIVE: The purpose of our study was to determine the temporal variability of regurgitant color Doppler jet areas and the width of the color Doppler imaged vena contracta for evaluating the severity of aortic regurgitation. METHODS: Twenty-nine hemodynamically different states were obtained pharmacologically in 8 sheep 20 weeks after surgery to produce aortic regurgitation. Aortic regurgitation was quantified by peak and mean regurgitant flow rates, regurgitant stroke volumes, and regurgitant fractions determined using pulmonary and aortic electromagnetic flow probes and meters balanced against each other. The regurgitant jet areas and the widths of color Doppler imaged vena contracta were measured at 4 different times during diastole to determine the temporal variability of this parameter. RESULTS: When measured at 4 different temporal points in diastole, a significant change was observed in the size of the color Doppler imaged regurgitant jet (percent of difference: from 31.1% to 904%; 233% +/- 245%). Simple linear regression analysis between each color jet area at 4 different periods in diastole and flow meter-based severity of the aortic regurgitation showed only weak correlation (0.23 < r < 0.49). In contrast, for most conditions only a slight change was observed in the width of the color Doppler imaged vena contracta during the diastolic regurgitant period (percent of difference, vena contracta: from 2.4% to 12.9%, 5.8% +/- 3.2%). In addition, for each period the width of the color Doppler imaged vena contracta at the 4 different time periods in diastole correlated quite strongly with volumetric measures of the severity of aortic regurgitation (0.81 < r < 0.90) and with the instantaneous flow rate for the corresponding period (0.85 < r < 0.87). CONCLUSIONS: Color Doppler imaged vena contracta may provide a simple, practical, and accurate method for quantifying aortic regurgitation, even when using a single frame color Doppler flow mapping image.

Animals↗
PubMed1998

Trichomonas tenax empyema in an immunocompromised patient with advanced cancer.

A 53-year-old male acromegalic patient with advanced rectal adenocarcinoma developed pleuritis in the course of cobalt irradiation, steroid treatment and chemotherapy. Examination of drained pleural fluid demonstrated numerous motile organisms, which were identified as Trichomonas tenax by Giemsa staining. Peptostreptococcus micros was also detected in the cultures of pleural fluid and blood. Treatment with metronidazole successfully eliminated the protozoa and cured the pyothorax.

Acromegaly↗
PubMed1998

The significance of plasma lysophospholipids in patients with renal failure on hemodialysis.

Abnormal phospholipid metabolism may play an important role in the progression of atherosclerosis in renal failure. We analyzed plasma phospholipid and lysophospholipid contents and fatty acid composition in the phospholipids of 18 patients with renal failure on hemodialysis (HD) and compared the levels with those of healthy controls. HD patients had a notably higher molar ratio of the plasma lysophosphatidylcholine (lysoPC)/phosphatidylcholine (PC) distributed from 0.072 to 0.207, and the control group showed a ratio lower than 0.150. Plasma phosphatidylethanolamine (PE) concentration significantly increased in HD patients compared with control subjects. A much higher level of plasma lysophosphatidic acid (lysoPA) (1.41 +/- 0.16 nmol/mL) was observed in HD patients compared with controls (0.54 +/- 0.08 nmol/mL). A strong correlation was found between plasma lysoPA and lysoPC concentrations (r = 0.609, p < 0.01) in HD patients. Serum inorganic phosphate (P) concentration was associated with the abnormal plasma lysoPC/PC, PE, and lysoPA levels in HD patients. Important decreases in eicosapentaenoic acid (EPA) of plasma PC and of dietary intake were observed in HD patients. Plasma thiobarbituric acid reactive substance (TBARS) concentration was negatively correlated with the amount of vitamin E intake in both subjects. These findings demonstrated the specific characteristics of the abnormal phospholipid metabolism in HD patients. The cause and consequences of elevated lysoPC/PC molar ratio and lysoPA in the plasma of HD patients remain to be established.

Adult↗
PubMed1998

A method for estimating aortic regurgitant effective orifice area by digital Doppler color flow mapping.

BACKGROUND AND AIMS OF THE STUDY: Although non-invasive assessment of the severity of aortic regurgitation (AR) is important, quantitative evaluation of AR can be difficult in clinical settings. Most Doppler echocardiographic methods have been compared with angiographic grading of AR severity. However, while aortic angiography is used widely for grading AR severity, the method is only semi-quantitative. A computed semi-automatic digital color Doppler method has recently been described for calculating stroke volume and cardiac output. The study aim was to develop a method of evaluating AR severity by using a digital automated color Doppler method (ACM) along with continuous wave (CW) Doppler for estimating aortic regurgitant effective orifice area. METHODS: A total of 22 different hemodynamic conditions were studied in six sheep. Regurgitant volumes (RV) were determined by electromagnetic flowmetry (EM) and by ACM. AR effective orifice areas (EOAs) were determined by dividing each of the RVs by the time integrals of the AR continuous wave velocities. AR EOAs by ACM were compared with those obtained by EM and with other EM indices of regurgitant severity. ACM was accurate for quantifying AR EOAs (r = 0.96). RESULTS AND CONCLUSIONS: Calculated AR EOA correlated well with peak AR flow and regurgitant fraction by EM. The combined ACM/CW Doppler method can be useful for estimating non-invasively the aortic regurgitant EOA and for evaluating the severity of AR.

Anatomy, Cross-Sectional↗
PubMed1997

Direct measurement of three-dimensionally reconstructed flow convergence surface area and regurgitant flow in aortic regurgitation: in vitro and chronic animal model studies.

BACKGROUND: Evaluation of flow convergence (FC) with two-dimensional (2D) imaging systems may not be sufficiently accurate to characterize these often asymmetric, complex phenomena. The aim of this study was to validate a three-dimensional (3D) method for determining the severity of aortic regurgitation (AR) in an experimental animal model. METHODS AND RESULTS: In six sheep with surgically induced chronic AR, 20 hemodynamically different states were studied. Instantaneous regurgitant flow rates were obtained by aortic and pulmonary electromagnetic flow meters. Video composite data of color Doppler flow mapping images were transferred into a TomTec computer after computer-controlled 180 degrees rotational acquisition. Direct measurement of the 3D reconstructed FC surface areas as well as measurements of FC areas estimated with 2D methods with hemispherical and hemielliptical assumptions were performed, and values were multiplied by the aliasing velocity to obtain peak regurgitant flow rates. There was better agreement between 3D and electromagnetically derived flow rates than there was between the 2D and the reference values (r=.94, y=1.0x-0.16, difference=0.02 L/min for the 3D method; r=.80, y=1.6x-0.3, difference=1.2 L/min for the 2D hemispherical method; r=.75, y=0.90x+0.2, difference=-0.20 L/min for the 2D hemielliptical method). CONCLUSIONS: Without any geometrical assumption, the 3D method provided better delineation of the FC zones and direct measurements of FC surface areas, permitting more accurate quantification of the severity of AR than the 2D methods.

Animals↗
PubMed1997

Vena contracta imaged by Doppler color flow mapping predicts the severity of eccentric mitral regurgitation better than color jet area: a chronic animal study.

OBJECTIVES: This study sought to evaluate the relation between the color Doppler-imaged vena contracta and the severity of mitral regurgitation (MR) in a chronic animal model of MR. BACKGROUND: The vena contracta, which is defined as the smallest connection between the laminar flow acceleration zone and the turbulent regurgitant jet, has been reported to be a clinically useful marker for evaluating the severity of valvular regurgitation. METHODS: Six sheep with chronic MR produced by previous operation severing the chordae tendineae were examined. MR jet flows and vena contracta widths were imaged using a Vingmed 775 scanner with a 5-MHz transducer. Image data were directly transferred in digital format to a microcomputer for off-line measurement. MR was quantified as peak and mean regurgitant flow rates, regurgitant stroke volumes and regurgitant fractions determined using mitral and aortic electromagnetic flow probes and flowmeters balanced against each other. RESULTS: Vena contracta width correlated well with regurgitant severity determined by electromagnetic flowmeters (r = 0.95, SEE = 0.05 cm, p < 0.0001 for peak regurgitant flow rate; r = 0.85, SEE = 0.08 cm, p < 0.0001 for regurgitant stroke volume; r = 0.90, SEE = 0.07 cm, p < 0.0001 for regurgitant fraction). CONCLUSIONS: This study shows that the vena contracta width method is useful for predicting the severity of MR. It is simple and conveniently available with high resolution equipment. The quantitative comparisons in the present study lay the foundation for future clinical and research studies using this vena contracta technique.

Animals↗
PubMed1997

Quantifying aortic regurgitation by using the color Doppler-imaged vena contracta: a chronic animal model study.

BACKGROUND: The aim of the present study was to evaluate the accuracy of determining aortic effective regurgitant orifice area (EROA) and aortic regurgitant volume by using the color Doppler-imaged vena contracta (CDVC). METHODS AND RESULTS: Twenty-nine hemodynamically different states were obtained pharmacologically in eight sheep with surgically induced aortic regurgitation. Instantaneous regurgitant flow rates (RFRs) were obtained with aortic and pulmonary electromagnetic flowmeters (EFMs), and aortic EROAs were determined from EFM RFRs divided by continuous wave Doppler velocities. Color Doppler-derived EROAs were estimated by measuring the maximal diameters of the CDVC. Peak and mean RFRs and regurgitant volumes per beat were calculated from vena contracta area continuous wave diastolic Doppler velocity curves. Peak EFM-derived RFRs varied from 1.8 to 13.6 (6.3+/-3.2) L/min (range [mean+/-SD]), mean RFRs varied from 0.7 to 4.9 (2.7+/-1.3) L/min, regurgitant volumes per beat varied from 7.0 to 48.0 (26.9+/-12.2) mL/beat, and the regurgitant fractions varied from 23% to 78% (55+/-16%). EROAs determined by using CDVC measurements correlated well with reference EROAs obtained by using the EFM method (r=.91, SEE=0.07 cm2). Excellent correlations and agreements between peak and mean RFR and regurgitant volumes per beat as determined by Doppler echocardiography and EFM were also demonstrated (r=.95 to .96). CONCLUSIONS: Our study indicates that the CDVC method can be used to quantify both aortic EROAs and regurgitant flow rates.

Animals↗
PubMed1997

Transballoon intravascular ultrasound imaging during balloon angioplasty in animal models with coarctation and branch pulmonary stenosis.

BACKGROUND: Intravascular ultrasound (IVUS) studies performed after balloon dilation provide a method for evaluating the adequacy of angioplasty and the nature of associated changes in vessel walls. Previously, IVUS studies required the use of separate scanning catheters inserted independently before and after balloon angioplasty. We tested a 0.035-in, 30-MHz IVUS transducer wire that images from within commercially available 5F balloon dilation catheters. METHODS AND RESULTS: Seven stenoses were created in the left pulmonary artery (n = 3) and in the aortic isthmus (n = 4) in six lambs (weight, 3.4 to 12.5 kg). The balloon catheter selected was advanced across the stenotic area and the IVUS wire advanced in the guide lumen to the center of the balloon. Continuous IVUS images were obtained through balloons before, during, and after dilation. Transballoon imaging confirmed balloon location within the stenotic segment. Luminal diameters of stenotic and adjacent vessel segments before and after angioplasty by IVUS showed good correlation with angiographic measurements (r = .93, P < or = .001). After successful dilation, imaging during deflation allowed the assessment of vascular elastic recoil, mural dissection, and luminal size without requiring changes in balloon position. Repeat dilation could be undertaken and the inflation pressure and technique modified on the basis of the observed results. CONCLUSIONS: This transballoon IVUS system provides important on-line information about lumen diameter and wall structure for evaluation of angioplasty without the need for catheter changes, providing a method to possibly reduce the likelihood of excessive wall damage and to potentially reduce the number of angiograms required to accomplish and confirm results.

Angiography↗
PubMed1997

Doppler echocardiographic evaluation of ventricular diastolic filling in fetuses with ductal constriction.

To assess ventricular diastolic filling in fetuses with constriction of ducts arterious, 43 fetuses of pregnant women receiving indomethacin (100 to 150 mg/day) were examined with Doppler echocardiography. Ductal constriction occurred in 21 fetuses, defined as maximal systolic velocity > 140 cm/s and diastolic flow velocity > 30 cm/s. The variables measured to assess diastolic function were peak velocity during early diastole (peak E wave), peak velocity during atrial contraction (peak A wave), and the velocity ratio (peak E/A ratio); these were compared to maximal ductal flow velocity during systole and diastole. The mitral peak E wave, peak A wave, and peak E/A ratio in fetuses with ductal constriction showed no significant difference from those in fetuses without ductal constriction. In fetuses with ductal constriction, the tricuspid A wave increased significantly without changes in the peak E wave (57 +/- 9 vs 50 +/- 6 cm/s, p < 0.01) and the peak E/A ratio was significantly lower than in fetuses without ductal constriction (0.57 +/- 0.10 vs 0.65 +/- 0.08, p < 0.05). In 9 fetuses with ductal constriction, we compared the Doppler tricuspid E wave, A wave, and E/A ratio during indomethacin administration with those after withdrawal of the drug for a mean of 24 hours. Both systolic and diastolic ductal flow velocities in the fetuses returned to normal range after discontinuation of indomethacin. The tricuspid peak A wave decreased (59 +/- 9 vs 50 +/- 11 cm/s) and the E/ A ratio increased significantly (0.56 +/- 0.07 vs 0.69 +/- 0.07) (both p < 0.01) without any significant change in peak E wave after discontinuation of indomethacin. This study suggests that ductal constriction influences Doppler patterns of right ventricular diastolic filling. These changes could be related to the increased afterload presented to the right ventricle which might affect diastolic function.

Anti-Inflammatory Agents, Non-Steroidal↗