[Clinical evaluation on the efficacy and usefulness of SI-3906].
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Evaluation Studies as Topic↗
Biomedical subjects
K Amano
Publications and source records attributed to K Amano.
[Aortic regurgitation in hypertrophic cardiomyopathy as detected by color Doppler echocardiography].
Aortic regurgitation (AR) in patients with hypertrophic cardiomyopathy (HCM) has rarely been reported. Using color Doppler echocardiography, we assessed the incidence and the cause of AR in patients with HCM. There were 86 patients with HCM (M:F = 66: 20, 57 +/- 12 years, mean +/- SD) and 43 control subjects (M: F = 33: 10, 57 +/- 8 years). HCM was diagnosed by echocardiography; the thickness of the interventricular septum (IVS) was more than 15 mm and the ratio to the thickness of the left ventricular free wall (LVPW) was more than 1.3. The rate and degree of aortic regurgitation were observed by color Doppler echocardiography, and aortic regurgitant murmurs were recorded by phonocardiography. Echocardiographic measurements were made using standard techniques. In the M-mode echocardiograms, the aortic diameter, the thicknesses of the IVS and LVPW were measured. In the 2DE, calcification of the aortic valve and systolic anterior movement of the mitral valve (SAM) were evaluated. In the early systolic 2DE image, the distance from the point of the greatest bulging of the upper IVS to the aortic root (D1) and the distance from the point of the greatest bulging to the line which is parallel to the long axis of the aorta (D2) were measured. Results were as follows: 1. Color Doppler echocardiography revealed aortic regurgitation in 17 (21%) patients with HCM; whereas it was observed in only three (7%) of the control subjects. 2. The aortic regurgitant signals were limited to the left ventricular outflow tract both in patients with HCM and in the control subjects. 3. Aortic regurgitant murmurs were recorded in only two patients with HCM and in none of the control subjects. 4. There was no difference between the patients with and without AR as to age (59 vs 56 years), blood pressure (141/84 vs 136/80 mmHg), aortic diameter (34 vs 33 mm), aortic valve calcification (12% vs 9%) and SAM (53% vs 52%). 5. In the patients with HCM, D1 was shorter (9.9 vs 14 mm, p less than 0.001) and D2 was longer (16 vs 10 mm, p less than 0.001) in the patients with AR than in those without AR. That is, the basal septum of the patients with AR protruded more deeply into the outflow tract, and the distance to the aortic valve was significantly shorter than in those without AR.(ABSTRACT TRUNCATED AT 400 WORDS)
Aged↗
[Left ventricular function at rest and during exercise and the effects of propranolol in patients with hypertrophic cardiomyopathy].
To determine left ventricular function during the stress of exercise and to evaluate the effects of propranolol on it in patients with hypertrophic cardiomyopathy (HCM), the ECG-multigated blood pool cardiac scintigraphy was performed in 12 without (HNCM) and 10 with (HOCM) left ventricular outflow obstruction at rest and during bicycle ergometer loading. The results were compared to those in 13 normal subjects. 1. Control measurements: Resting and exercise heart rates and blood pressures did not significantly differ between patients with hypertrophic cardiomyopathy and normal subjects. Ejection fraction (EF) was normal or higher in HCM than in normal subjects at rest, but during exercise it failed to increase normally. The increment in cardiac output was half of the normal value. Responses of count-derived end-diastolic volume (EDV) and stroke volume (SV) were different between HOCM and HNCM. They were unchanged during exercise in HNCM and declined in HOCM. End-systolic volume (ESV) was unchanged in HNCM and slightly decreased in HOCM. Responses of the peak ejection rate (PER) and time to the peak ejection rate (TPE) were not significantly different from normal subjects. Left ventricular (LV) ejection time (ET) and TPE/ET were not different from normal subjects. The peak filling rate (PFR) was significantly higher than normal in HOCM at rest and during exercise. The time to peak filling rate was prolonged at rest in HOCM, but not during exercise. 2. Effects of propranolol: Heart rates significantly decreased especially after intravenous propranolol administration. Cardiac output (CO) and SV were unchanged. EDV and ESV increased significantly. The PER was unchanged. The PFR decreased, but not significantly. TPE, time to the PFR (TPF) and ET were prolonged. The ratio of TPE/ET decreased initially, but abruptly increased later. In conclusion, in the control state of HCM patients, the responses of LVEF, EDV and ESV to exercise were abnormal and CO remained half of the normal. There was no difference between patients with and without obstruction. The effect of propranolol on left ventricular function was more obvious in patients with obstruction than without obstruction, especially in ESV, EDV, PFR and TPF. Propranolol did not improve LV systolic and diastolic functions, but the double product decreased depending on the decrease of heart rate maintaining CO by Frank-Starling mechanism due to increased EDV, which may play a part in improving subjective complaints.
Administration, Oral↗
[CT-guided stereotactic brachytherapy in deep-seated malignant gliomas--interstitial irradiation by double-catheter after-loading method].
CT-guided stereotactic brachytherapy has been performed for the deep-seated malignant gliomas using the double-catheter after-loading method. The catheter system consists of two coaxial polyethylene tubes with closed tips. The outer catheter is 3.0 mm in outer diameter and 2.4 mm in inner diameter. The inner catheter is 2.0 mm in outside diameter and 1.4 mm in inside diameter, and contains the radioactive sources. Localization of the target volume is determined by the preoperative findings of computed tomography (CT), magnetic resonance imaging (MRI), and cerebral angiography. Dosimetry and dose planning are so finalized for the target volume as to be irradiated interstitially more than tumoricidal dose. After stereotactic biopsy of the deep-seated brain tumors, stereotactic implantation of the outer catheters is performed using Iseki Stereotactic System in the CT room. Burr holes had been previously opened in the operating room. The inner catheters containing nonradioactive sources (dummy sources) are inserted, and skull X-p is taken to confirm the position of the dummy sources, and to calculate the dosimetry by computer. The inner catheters are replaced with catheters containing radioactive sources (226Ra) in the irradiation room. 226Ra sources deliver at least 500 rads/day (approximately 20 rads/hr) to the target volume as interstitial irradiation. Two patients of malignant gliomas treated with this procedure were shown as representative cases. These patients underwent CT-guided stereotactic brachytherapy as "boost" combined with conventional external irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[EEG topographic changes of brain abscesses in children].
EEG topography was investigated before and after surgical treatment in 4 patients with brain abscess aged from 5 to 13 years. According to the recording technique designed by Matsuoka and Ueno, the recorded EEG for each 5 seconds was analyzed to obtain square roots of power spectra for each band of delta (2-3.8 Hz), theta (4-7.8 Hz) and alpha (8-12.8 Hz) which were then added for the 60-seconds duration of each trial. After that, numerical matrix presenting the topographic distribution of spectral energy of each band were constructed and displayed as color images. In addition, the EEG topographies of brain abscesses were compared with the CT scans simultaneously obtained. In all of four cases before surgical treatment of the brain abscess, the location of the focal delta wave on the EEG topography was more closely related to the site of brain abscess comparing with its correlation between the location of the delta focus on the conventional EEG and the site of brain abscess. In contrast, as for the theta wave, there was no prominent correlation to the site of the brain abscess. In the early stage of 10-15 days after aspiration of the brain abscess, the most characteristic change of the EEG topography was an approximately 25% reduction of the maximum equivalent voltage of delta band with associated disappearance of the sharply located focal delta wave being noted before aspiration.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Relationship between microflora of the upper small intestine and steatorrhoea in patients with extensive gastric resection].
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Adult↗
[An analysis of islet cell surface antigen defined by monoclonal islet cell surface antibody 5C12].
Monoclonal antibody 3A4 to islet cell surface antigen has been previously established in our laboratory, using hybridization of spleen lymphocytes from non-obese diabetic (NOD) mice transferred into immunologically incompetent recipient mice. In the present study, monoclonal islet cell surface antibody 5C12 could be newly obtained in the 10:1 ratio of NOD mice spleen cells and mouse myeloma cells (SP2/0) without any modifications. Protein A radioligand assay and indirect immunofluorescence on living cells showed that 5C12 antibody reacted to normal rat islet cells and cultured rat insulinoma cells (RIN-r), but not to cultured lymphocytes (Bri-7, IM-9) and Chang-liver cells. Analysis of 125I-labeled antibody binding revealed that unlabeled 5C12 effectively inhibited subsequent 125I-5C12 binding to RIN-r cells, whereas unlabeled 3A4 did not. The scatchard plot from these data showed the curvilinearity, and about 150,000 binding sites to antibody per RIN-r cell were counted. The treatment of RIN-r cells with papain and neuraminidase reduced the binding of 5C12 to RIN-r cells, whereas the effect of trypsin was not observed. Immunoprecipitation of 125I-labeled insulinoma cell lysates followed by SDS-PAGE and autoradiography indicated that 5C12 recognized 105K dalton cell surface protein in RIN-r cells. Immunoblotting also showed that 5C12 antibody recognized 105K dalton cell surface protein in RIN-r cells. These results demonstrated that 5C12 was an important tool for clarifying the immunoresponse against certain antigenic determinants on pancreatic B cells. Furthermore, 5C12 has not only qualitatively and quantitatively improved diagnostic methodology, but it may also provide new reagents useful to the treatment and prevention of type 1 diabetes.
Animals↗
DNA-daunorubicin complexes specifically suppress in vitro spontaneous anti-DNA antibody production in lymphocytes of patients with systemic lupus erythematosus.
Elevated production of anti-DNA antibody in patients with systemic lupus erythematosus (SLE) is a central problem in the pathogenesis of tissue injury. In the present study, we attempted to manipulate anti-DNA antibody production through the antigen-cytotoxic drug conjugates, DNA-daunorubicin complexes. The effect of DNA-daunorubicin complexes was determined by examining SLE lymphocytes for spontaneous in vitro production of anti-DNA antibody. These complexes, at 2 micrograms/ml, suppressed anti-DNA antibody production, but not total IgG production, which suggests that specific suppression of anti-DNA antibody production was achieved at this concentration. We believe that the DNA-daunorubicin complexes affected mainly B cells, since such suppression was obtained by treating B cells, as well as B plus T cells. Furthermore, the complexes had no effect on the proliferative responses of SLE T cells to DNA, phytohemagglutinin, or concanavalin A. These results indicate that DNA-daunorubicin complexes may have the potential for selectively suppressing anti-DNA antibody production in patients with SLE.
Antibodies, Antinuclear↗
Noninvasive study of the presystolic component of the first heart sound in mitral stenosis.
Echophonocardiography and pulsed Doppler echocardiography were performed in 30 patients with mitral stenosis (19 with atrial fibrillation and 11 with sinus rhythm) to investigate the genesis of the presystolic component or small apical vibrations preceding the first heart sound in mitral stenosis. In 27 patients, mitral valve closure preceded or coincided with tricuspid valve closure regardless of the preceding RR interval. Of three patients whose tricuspid valve closed prematurely, two had a prolonged PR interval. The soft apical vibrations, which were recorded during the final rapid closing motion of the mitral valve echogram (B-C slope), began with the upstroke of the apexcardiogram. During this event the pulsed Doppler echocardiogram revealed a deceleration in the velocity of mitral inflow. In two exceptional patients with a prolonged PR interval, this apical sound was separated from a presystolic rumble that occurred during an accelerated phase of mitral inflow or at the A wave of mitral valve echograms. In conclusion, the tricuspid valve is not a factor contributing to the genesis of the small apical vibrations preceding the first heart sound in mitral stenosis. These vibrations are caused by acceleration of left ventricular contraction and deceleration of mitral inflow in the presence of a stenotic valve.
Adult↗
Direct demonstration of immunoregulatory T-cell defects in patients with systemic lupus erythematosus.
The present study was undertaken to determine directly whether immunoregulatory T cells have a defective suppressor function in patients with systemic lupus erythematosus (SLE), and whether anti-T-cell antibodies are essential for immunoregulatory T-cell defects. Peripheral blood T cells and T-cell subsets were determined in 52 SLE patients. The ratio of T4 to T8 cells was distributed over a wider range in patients with SLE than in the controls. Patients with SLE were divided into three groups (low, normal and high) by the T4/T8 ratio. Lymphocytes from 12 SLE patients (7 with low and 5 with high T4/T8 ratios) were studied extensively. Their disease was inactive or in remission. Anti-T-cell antibodies were not detected, and yet the patients had immunological abnormalities characterized by the presence of antinuclear antibodies and hypergammaglobulinaemia. The SLE patients with high T4/T8 ratios had a decreased number of T8 cells, and defective suppressor-effector cells. In contrast, patients with low T4/T8 ratios had decreased T4 cells and/or increased T8 cells, and defective suppressor-inducer cells. Two patients with low T4/T8 ratios had both suppressor-effector and suppressor-inducer cell defects. These results indicate that immunoregulatory circuits in SLE patients are heterogeneous and that immunoregulatory defects exist even when the disease is inactive or in remission. Anti-T-cell antibodies were not essential for such immunoregulatory defects. Thus, immunoregulatory T-cell defects and the development of SLE may be independent conditions due to other unknown causes.
Adult↗
Characterization of a phase I Coxiella burnetii chloroform-methanol residue vaccine that induces active immunity against Q fever in C57BL/10 ScN mice.
The effect of phase I Coxiella burnetii chloroform-methanol residue vaccine (CMRV) on the response of murine splenic lymphocytes to mitogenic and antigenic stimuli was evaluated in C57BL/10 ScN endotoxinnonresponder mice with an in vitro lymphocyte proliferation assay. Intraperitoneal injection of phase I CMRV resulted in antibody production against phases I and II antigens. Lymphocytes were responsive in vitro to concanavalin A, phytohemagglutinin, pokeweed mitogen, and specific recall antigens. Antibodies against phases I and II antigens were not detected after intraperitoneal injection of chloroform-methanol extract (CME). Lymphocytes also were only slightly hyporesponsive to mitogens. Reconstitution of the CMRV with the CME of phase I whole cells restored the immunopathological reactions that were associated with the phase I whole cell vaccine (WCV). The CMRV was more mitogenic than the WCV for lymphocytes from mice injected with saline. Lymphocytes from phase I WCV-injected mice were negatively modulated with nontoxic concentrations of homologous WCV or CMRV. Lymphocytes from phase I CMRV-injected mice were only slightly hyporesponsive to mitogens and were significantly stimulated by antigens of either WCV or CMRV as recall antigens. Vaccination of mice with 100 micrograms of CMRV, CME, or WCV provided 80, 0, or 50% protection, respectively, against a lethal intraperitoneal challenge with viable phase I C. burnetii. The epitopes which induce immunological hyporesponsiveness, negative modulation, and the death of lymphocytes were fractionated into the CMRV and CME. The CMRV provides at least one of the determinants which induce immunosuppression, whereas CME contains specific or nonspecific components or both. Collectively, these results show that the CMRV may be a potential candidate to replace the WCV currently used for human vaccination.
Animals↗
Asymmetric apical hypertrophy: ten years experience.
This paper reports 10 years experience of 31 patients with asymmetric apical hypertrophy, in whom left ventricular hypertrophy involved the apex exclusively and giant T wave inversion in the left precordial leads was the characteristic finding. This type of hypertrophic cardiomyopathy was observed predominantly in men over 40 years of age. Family history was negative and patients usually had no complaints. Left ventricular hypertrophy was evident by physical examination as in other forms of hypertrophic cardiomyopathy, but a systolic murmur was faint or absent and the second heart sound was frequently split. Electrocardiographic signs may fluctuate, and occasionally progression or regression occurs. Echocardiography including the two-dimensional method was essential for the diagnosis and left ventriculography was helpful for confirmation. To date complications have been infrequent and the prognosis seems good. The relation of asymmetric apical hypertrophy to other forms of hypertrophic cardiomyopathy is under investigation.
Adult↗
Long-term follow-up study of rostral mesencephalic reticulotomy for pain relief--report of 34 cases.
A long-term follow-up study of rostral mesencephalic reticulotomy (RMR) for pain relief is presented. 34 patients (24 males and 10 females) were operated. Ages ranged from 18 to 65 years. The follow-up period was 1-70 months. The overall effectiveness of RMR showed good relief of pain in 23 patients (67%). The study of effectiveness of RMR according to type of pain showed good relief of pain in 5 out of 6 patients (83%) with nondenervation pain, whereas satisfactory pain relief was obtained in 18 out of 28 patients (64%) with denervation pain.
Adolescent↗
Degradation of insulin by insulin-degrading enzyme and biological characteristics of its fragments.
We have previously reported on the purification, characterization, and biological significance of insulin-degrading enzyme (IDE) from pig and rat skeletal muscle. In the present study, we have investigated the detection and the HPLC separation of degradation products of native insulin from the reaction of monocomponent porcine insulin with affinity-purified pig IDE. Insulin was degraded by IDE in a time- and dose-dependent manner. Eight peaks (peaks I through VIII) appeared after 1 h of incubation, and peak V was identified as insulin. Among seven peaks representing degradation products, peak VI appeared most rapidly at 30 sec of incubation, increased until 10 min, and then decreased after 15 min of incubation; and six degradation products other than peak VI were not detected within 15 min of incubation, suggesting that peak VI was an initial degradation product of insulin produced by IDE and converted into relatively low molecular weight products as incubation time increased. The generation of peak VI may be due to cleavage at a peptide bond between the interchain disulfide bonds of the A or B chain. Subsequently, the split insulin derivative (peak VI) was evidently further degraded to relatively low molecular weight intermediates, such as peaks III and IV, peaks II and VIII, or peaks I and VII, because these pairs of peaks appeared and were degraded concomitantly. The peptide products designated as peaks IV, VI, VII, and VIII had both immunoprecipitability by antiinsulin antibodies and binding capacity to IM-9 lymphocytes, whereas the less hydrophobic intermediates (peaks I, II, and III) did not have these activities. Since some of these peptides have insulin-like properties, amino acid analysis of these products may enable us to identify not only the splitting position of insulin by IDE but also the site of the hormone for receptor binding.
Animals↗
Immunochemical characterization of anti-islet cell surface monoclonal antibody from nonobese diabetic mice.
We have produced a monoclonal antibody 3A4 to the surface of islet cells by fusing spleen lymphocytes from nonobese diabetic (NOD) mice. To identify the molecular weight of specific target antigens reacting with 3A4, 125I-surface-labeled In-111 insulinoma cells were solubilized and extracts were absorbed with 3A4, and immunoprecipitates were followed by polyacrylamide gel electrophoresis and autoradiography. 3A4 recognized two major polypeptides with apparent molecular weights of radioactive 64K and inactive 28K. In order to evaluate the antibody-mediated cytotoxic mechanisms of 3A4, complement-dependent antibody-mediated cytotoxicity (C'-AMC) and antibody-dependent cellular cytotoxicity (ADCC) were tested using a method of specific 51Cr release. In the study for C'-AMC, even over wide ranges of concentration of antibody and rabbit complement, purified 3A4 had no apparent cytotoxic effects on In-111 cells. On the other hand, significant ADCC was observed at an antibody concentration of 10 micrograms/ml and a target:effector cell ratio of 1:40 (P less than 0.01). Finally, the effects of 3A4 on glucose-stimulated insulin release were examined in isolated rat islets. At a glucose concentration of 16.7 mM, 3A4 significantly inhibited the insulin release either in the presence or absence of complement (P less than 0.01). In conclusion, 3A4 could not only bind but also be active to the target cells. Therefore, this monoclonal antibody should be a useful tool to permit a detailed analysis of the pathogenesis of type I diabetes mellitus.
Animals↗
[Diabetic cardiomyopathy in mild diabetics: evaluation by thallium-201 scintigraphy and exercise radionuclide ventriculography].
Forty mildly diabetic men, with a mean age of 49 +/- 9.7 years, and without clinical or exercise electrocardiographic evidence of ischemic cardiac disease, participated in a study consisting of exercise thallium-201 myocardial scintigraphy and exercise radionuclide ventriculography. 1. Among the 40 patients, 16 (40%) showed no filling defect (negative cases). Mild defects (mild cases) and moderate defects (moderate cases) were observed in 12 and 12 cases, respectively. 2. The percent washout ratio was decreased in none of the 16 negative cases, in three of the 12 mild cases, and in 11 of the 12 moderate cases. 3. There were no significant statistical differences in age, duration of diabetes, fasting blood sugar, HbA1c, serum cholesterol, smoking or blood pressure. Percent of ideal body weight was greater in moderate cases (121 +/- 15%) compared to negative or mild cases (103 +/- 9%, 108 +/- 9%) (p less than 0.01). 4. The percent fractional shortening was decreased in mild cases and in moderate cases (34.6 +/- 6.3%, 32.6 +/- 8.4%) compared to negative cases (41.7 +/- 4.9%) (p less than 0.01). Weissler's index (PEP/ET) was higher in moderate cases (0.42 +/- 0.09) compared to negative or mild cases (0.35 +/- 0.05, 0.36 +/- 0.06) (p less than 0.05). 5. Left ventricular wall motion was abnormal on echocardiography in none of the 16 negative cases, in three of the 12 mild cases and in seven of the moderate cases. The site of echocardiographically abnormal wall motion coincided with the defect area on myocardial scintigraphy in six cases, but not in four cases. 6. Radionuclide ventriculographic studies statistically showed no significant differences in ejection fraction (EF), 1/3EF, time to peak ejection (TPE), ejection time (ET), peak ejection rate (PER), 1/3 filling fraction (FF), 1/3 peak filling rate (PFR) and time to peak filling (TPF). The peak filling rate (PFR) at rest was significantly lower in mild cases (2.4 +/- 0.5 EDV/sec, p less than 0.025). Although the PFR at rest in moderate cases was lower than in negative cases (2.9 +/- 0.6 EDV/sec, 3.2 +/- 0.7 EDV/sec), no significant difference was shown between them. The rate of increase in cardiac output was significantly lower in moderate cases compared to mild cases and negative cases (59 +/- 28%, 96 +/- 49%, 97 +/- 31%, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
[A new treatment of hypertensive intracerebral hematoma--a follow-up study on 46 patients with hematoma treated by CT guided stereotactic method].
During the last 2 years, 46 cases of hypertensive intracerebral hemorrhage in the basal ganglia were treated by CT guided stereotactic aspiration and their outcome was evaluated in terms of the rate of hematoma removal, the change of consciousness level and the recovery of motor and sensory functions. They are aged from 45 to 79 years old, the average 56, and aspirated 1 to 24 days after the onset, two third of them being within 1 week. The whole procedure was done in the CT room under direct CT guidance and by one trial. In putaminal type hemorrhage, the removed hematoma volumes ranged from 9 to 48 ml, average being 23.7 ml, in thalamic type from 5 to 29 ml, average being 15.5 ml. The average rate of removal was 81.1% in 30 cases within 1 week. In most cases, preoperative consciousness was not severely disturbed, in putaminal type, 19 were alert or confused, 4 somnolent, 5 stuperous and in thalamic type, 6, 6, 3 respectively and 2 were semicomatous, one of them had herniation sign. In putaminal type all but 2 cases recovered to alert or confused state, the first one had postoperative bleeding and the other was already apallic preoperatively. In thalamic type, we lost 3 cases, 2 by gastrointestinal bleeding and 1 DIC, by rehemorrhage 2 months after the operation. All but one who was semicomatous preoperatively recovered to alertness. In motor function, some cases of the putaminal bleeding with intact internal capsule remained hemiplegic. On the other hand, most of the cases with partial destruction of the internal capsule on CT recovered well in both types of hematoma.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Clinical significance of early or mid-systolic apical murmurs: analysis by phonocardiography, two-dimensional echocardiography and pulsed Doppler echocardiography.
The records of 2,000 consecutive patients who had been examined by auscultation, phonocardiography (PCG), two-dimensional echocardiography and pulsed Doppler echocardiography (PDE) were reviewed to assess the clinical significance of apical systolic murmurs which cease well before the aortic closure sound. Fifty-five patients were verified to have early or mid-systolic apical murmurs. Mitral regurgitation (MR) was detected in 32 patients by PDE (29/32) and/or PCG with methoxamine test (27/32). The degree of MR was judged to be mild by PDE in all cases. Apical systolic murmurs due to MR began mainly with the first heart sound (27/32), were confined to the apex (27/32), and high-pitched (25/32). Their intensity was grade III/VI or less in all cases. Mitral valve prolapse (12 patients) was the most common cause of MR. Other causes were rheumatic mitral involvement in seven patients, dilated or ischemic cardiomyopathy in five, mitral annular calcification in three, and hypertrophic cardiomyopathy in two. The causes of the MR in the remaining three patients could not be identified. Thus, early or mid-systolic apical murmurs are mainly attributable to mild MR which can be diagnosed by careful auscultation, PDE and/or PCG with the methoxamine test.
Adult↗