Estrogen-induced proliferation in cultured hepatocytes involves cyclin D1, p21(Cip1) and p27(Kip1).

The purpose of this study was to establish if estrogen-induced hepatocyte proliferation in vitro involves the cell cycle regulators cyclin D1, p21(Cip1), and p27(Kip1). Male rat hepatocytes were cultured in presence of 17-beta-estradiol (E2) +/- ICI-182780, a pure estrogen antagonist, and [3H]-thymidine, as required. DNA synthesis as well as p21(Cip1), p27(Kip1), and cyclin D1mRNA and protein levels were evaluated at different times (12, 24, 36, and 48 hours) of incubation. E2-increased DNA synthesis was correlated with cyclin D1 and p21(Cip1) (mRNA and protein) variations that were reversed by the addition of ICI-182780. p27(Kip1) protein levels progressively increased regardless of the presence of E2 or ICI-182780. Our data confirm that estrogens' stimulatory effect is related to their ability to increase cyclin D1 levels. The increase of p21(Cip1) is probably related to the reentry of hepatocytes in the quiescent state. p27(Kip1) protein is not able to arrest hepatocyte proliferation.

Effect of atrial fibrillation on pulmonary venous flow patterns: transoesophageal pulsed Doppler echocardiographic study.

The effect of atrial fibrillation on pulmonary venous flow patterns is still not well known. Twenty-four patients in atrial fibrillation and 21 patients in sinus rhythm were studied by transoesophageal echocardiography. In ninety-five percent (20/21) of sinus rhythm patients, the early systolic wave due to atrial relaxation or reverse wave due to atrial contraction could be distinguished on pulsed Doppler tracings by transoesophageal echocardiography. However, there was no early systolic wave and/or reverse at the end of diastole in any atrial fibrillation patients. In atrial fibrillation patients without mitral regurgitation (n = 14), the onset of systolic flow was delayed (165 +/- 38 vs 50 +/- 46 ms, P < 0.05), and systolic peak velocities, time-velocity integrals and systolic fractions were reduced (31 +/- 13 vs 54 +/- 17 cm.s-1, P < 0.05; 5 +/- 2 vs 13 +/- 6 cm, P < 0.05 and 36 +/- 8 vs 61 +/- 15%, P < 0.05, respectively) as compared to those in sinus rhythm. Significant mitral regurgitation (n = 10) reduced systolic velocity parameters considerably in atrial fibrillation patients but the diastolic flow parameters were not significantly different between sinus rhythm and atrial fibrillation patients. Stepwise multiple regression analysis identified atrial fibrillation as an important independent predictor for changes in systolic flow parameters. The R-R interval is also an important factor for diastolic flow parameters. Thus, the present study demonstrates that atrial fibrillation significantly modifies pulmonary venous flow pattern and is an important factor for systolic flow parameters. Significant mitral regurgitation can further modify systolic flow pattern in atrial fibrillation patients.

Familial dilated cardiomyopathy: a transverse and longitudinal clinical and echocardiographic study.

The familial occurrence of hypertrophic cardiomyopathy is well known; familial dilated cardiomyopathy has so far received less attention. Ten families with two or more members affected by dilated cardiomyopathy were studied by echocardiography. In 3 out of 10 families, a transverse study extended to even apparently healthy subjects was carried out, which included a total of 45 subjects. In 19 out of the 45, dilated cardiomyopathy (either symptomatic or asymptomatic) was diagnosed at echocardiography. Three more relatives, already dead of the disease, were identified through hospital records. A clinical and echocardiographic longitudinal study, lasting up to 11 years, was carried out in 5 of the 10 families. During the follow-up, 8 out of 19 patients who, at first examination were affected by dilated cardiomyopathy, died, one improved, 3 remained in stable condition and 7 were lost at follow-up. One of two patients who presented echocardiographic findings suggestive of border-line dilated cardiomyopathy returned to normality and the other developed dilated cardiomyopathy. The clinical and echocardiographic findings in our patients, and in their relatives, suggest the possibility that idiopathic dilated cardiomyopathy may be a multifactorial disease in which genetic factors might play a variable role.

Quantification of mitral regurgitation: comparison between transthoracic and transesophageal color Doppler flow mapping.

We reviewed transthoracic (TTE) and transesophageal (TEE) echocardiograms of 100 consecutive patients: 63 male, 37 female, mean age 50 years (range 16-83 years), 32 with neoplastic disease, 18 aortic disease, 28 mitral valve disease, and 22 with other diseases. Absence or presence of mitral regurgitation (defined as mild, moderate, or severe) was assessed. TEE showed mild mitral regurgitation in 26 patients where TTE was negative. The overall estimate of regurgitant lesion severity was concordant at TEE and TTE in 64% of cases. The overall estimate of regurgitant lesion severity was also greater by one grade in 1% of cases at TTE, and in 35% of cases at TEE. Maximal digitized jet areas were 3.60 +/- 6.35 cm 2 at TTE and 3.04 +/- 3.79 cm 2 at TEE (P = NS). Correlation was r = 0.69 (TEE = 0.41 TTE + 1.55; P less than 0.001). TEE yielded a higher prevalence of mitral regurgitation than TTE with a trend toward greater overall estimate of mitral regurgitation at the semi-quantitative analysis. TTE and TEE showed similar mean results at the quantitative assessment of maximal jet areas. However, a highly significant random variability was observed in quantifying mitral regurgitation at TEE.

Sodium-lithium countertransport and cardiorenal abnormalities in essential hypertension.

The rate of red blood cell sodium-lithium countertransport is elevated only in a subgroup of patients with essential hypertension. We have therefore compared renal and cardiac function and morphology in two groups of hypertensive patients with high (n = 23) or normal (n = 22) sodium-lithium countertransport (mean +/- SEM: 0.61 +/- 0.10 versus 0.29 +/- 0.07 mmol/l red blood cells.hr). The two groups were similar in age, sex distribution, body mass index, smoking habit, duration of hypertension, and actual levels of untreated blood pressure. Hypertensive patients with elevated sodium-lithium countertransport activity showed elevated glomerular filtration rate (118 +/- 2 versus 109 +/- 2 ml/min.1.73 m2; p less than 0.001), albumin excretion rate (23 +/- 3 versus 14 +/- 2 micrograms/min; p less than 0.001), larger kidney volume (250 +/- 15 versus 203 +/- 13 ml.1.73 m2; p less than 0.01), lower lithium clearance rate (26.7 +/- 0.3 versus 28.9 +/- 0.3 ml/min.1.73 m2; p less than 0.01), and higher total body exchangeable sodium (2,716 +/- 33 versus 2,485 +/- 41 mmol.1.73 m2; p less than 0.01). Left ventricular mass index (139 +/- 6 versus 119 +/- 6 g/m2; p less than 0.05), relative wall thickness (0.39 +/- 0.05 versus 0.29 +/- 0.04 cm; p less than 0.001), and left posterior wall plus intraventricular septum thickness (2.02 +/- 0.04 versus 1.76 +/- 0.03 cm; p less than 0.05) were also higher in patients with high sodium-lithium countertransport. Hypertensive patients with normal sodium-lithium countertransport had renal and cardiac parameters similar to those of a normotensive control group (n = 21) except for a higher glomerular filtration rate and left ventricular mass index.(ABSTRACT TRUNCATED AT 250 WORDS)

Transthoracic and transoesophageal echocardiographic documentation of disappearance of massive right atrial and pulmonary artery thromboemboli after fibrinolytic therapy and normalization of left ventricular dimensions and function.

In this paper, we report a case of dilated cardiomyopathy with right atrial thrombi and pulmonary artery thromboemboli, in which regression of thromboemboli followed fibrinolytic therapy, and normalization of left ventricular dimensions and function were documented at echocardiographic follow-up. The important role of transoesophageal echocardiography in diagnosis and follow-up of right intracavitary masses and thromboemboli in the main pulmonary arteries is discussed, as is the role of echocardiography in follow-up of cardiomyopathy.

[Color Doppler identification of early diastolic turbulence in the left atrium in patients with mitral valve insufficiency: persistence of regurgitation or inertia phenomenon?]. / Turbolenza protodiastolica in atrio sinistro al color Doppler in pazienti con insufficienza mitralica: persistenza del rigurgito o fenomeno inerziale?

Color Doppler flow mapping represents the most recent non invasive diagnostic tool for the visualization of intracardiac blood flow. By using the color Doppler flow mapping technique, two independent observers identified the persistence of turbulence in early diastole inside the left atrium in a selected group of 8 patients (3 F and 5 M) with mitral insufficiency. All the patients had moderate or severe mitral insufficiency, due to dilated cardiomyopathy and/or ischemic cardiomyopathy and/or valvular disease. The persistence of early diastolic turbulence inside the left atrium was documented and confirmed by using 30 degrees color sector images, which show the highest possible frame rate. The frame by frame analysis facilitated the identification of two simultaneous flow velocities during early diastole, after the mitral valve was open. The first flow was anterograde and was coded as a red signal; it flowed from the mitral valve into the left ventricle and represented early diastolic left ventricular filling. The second flow was retrograde, and was coded as a blue mosaic signal, due to turbulent aliased jet, extending from the mitral valve into the left atrium, away from the transducer. The interpretation of these two dimensional color Doppler findings is uncertain. We believe, however, that these turbulent velocity signals which persist in early diastole and flow from the mitral valve into the left atrium are probably caused by inertial blood flow due to the impact of regurgitant mitral jets during the previous systole.

[Apical hypertrophic cardiomyopathy: variability of bidimensional echocardiographic and electrocardiographic expression]. / Cardiomiopatia ipertrofica apicale: variabilità di espressione ecocardiografica bidimensionale ed elettrocardiografica.

Apical hypertrophic cardiomyopathy is characterized by primary hypertrophy of the myocardium which is localized exclusively at the apex of the left ventricle. Previous studies have indicated that apical hypertrophic cardiomyopathy is characterized by a unique combination of cross-sectional echocardiographic and ECG findings ("giant" T wave inversion and high R wave voltage in the precordial leads). The aim of this study was to evaluate the possible relation between apical hypertrophy, quantitatively defined by cross-sectional echocardiography, and ECG findings in patients with apical hypertrophic cardiomyopathy. We studied 13 pts with apical hypertrophic cardiomyopathy, 10 men and 3 women (aged between 11 and 73 years, mean age 47). Apical hypertrophy was assessed quantitatively by determinating the muscle cross-sectional area in the apical region. From the end-diastolic apical 4 chamber view, endocardial and epicardial contours were digitized in order to obtain the muscle cross-sectional area of the left ventricle. The walls of the left ventricle were then divided into 3 regions (basal, mid-ventricular, apical). Final values of planimetered muscle areas are given as the average of the calculations obtained blindly and independently by 4 observers. The comparison between cross-sectional echocardiographic and electrocardiographic findings showed that patients with giant T wave inversion (T wave greater than 10 mm) and high R wave voltages (R greater than wave 25 mm) had a more severe degree of apical hypertrophy. However there was no complete agreement between cross-sectional echocardiographic and electrocardiographic findings. This study in fact demonstrates a wide variation in the degree of severity of apical hypertrophy among patients with apical hypertrophic cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Interobserver and echo-angio variability of two-dimensional colour Doppler evaluation of aortic and mitral regurgitation.

Colour Doppler flow mapping (CD) has proved to be a very sensitive and specific means of diagnosing valvular regurgitation and obtaining a rapid semiquantitative estimation of the severity of regurgitation itself. We tried to compare a semiquantitative evaluation of aortic and mitral regurgitation, without time-consuming calculations of regurgitant jet areas, with the conventional visual semiquantitative angiographic estimation. We have also evaluated in detail the interobserver variability of this type of semiquantitation. Two independent observers (OB) have reviewed CD studies of a selected group of 47 consecutive patients who underwent both cineventriculography and aortography for aortic regurgitation (AR) and/or mitral regurgitation (MR), then graded as mild, moderate or severe. At CD, AR and MR were classified as present or absent and graded as mild, moderate or severe. The following interobserver percentage agreements were noted for AR presence or absence, AR grade, MR presence or absence, MR grade, respectively: 96%, 83%, 96%, 83%. Likewise, the respective echo-angio agreements were 90%, 58%, 80%, 70%. Agreement was significant (P less than 0.001) in all cases. Thus, good interobserver and echo-angio agreement was found in the CD assessment of AR and MR. However, under- or overestimation of CD vs. angio was noted in several cases (mostly by one grade). Underestimation of CD vs. angio was 27% for AR and 18.5% for MR; overestimation of CD vs. angio was 15% for AR and 11.5% for MR. CD has proved to be a useful technique not only for the qualitative but also for the semiquantitative evaluation of aortic and mitral regurgitation, as assessed in the same subjects, with good interobserver agreement.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiographic findings of left ventricular hypertrophy and normalization of parameters of left ventricular function in patients with previous evidence of dilated and poorly contracting left ventricle and coexisting systemic hypertension.

We report 6 cases of dilated left ventricle with poor left ventricular function and coexisting systemic hypertension in whom left ventricular hypertrophy and normalization of left ventricular function and dimensions have been subsequently documented by M-mode and two-dimensional echocardiographic follow-up studies. Four patients were in New York Heart Association functional Class IV, one in Class III, and one in Class II when first seen. Normalization of left ventricular function and dimensions and features of left ventricular hypertrophy (fractional shortening from 15.0 +/- 5.2 to 39.7 +/- 5.4, left ventricular end-diastolic diameter from 6.6 +/- 0.6 to 4.6 +/- 0.6 cm, left ventricular end-systolic diameter from 5.6 +/- 0.8 to 2.8 +/- 0.6 cm, left ventricular end-diastolic radius/posterior wall thickness from 3.1 +/- 0.5 to 2.0 +/- 0.4, interventricular septum thickness from 1.2 +/- 0.3 to 1.5 +/- 0.3 cm, left atrium from 4.6 +/- 0.6 to 3.5 +/- 0.9 cm) were achieved after adequate medical treatment at the end of the follow-up (11-39 months). It appears from this study that normalization of left ventricular dimensions and function with features of left ventricular hypertrophy can occur after adequate treatment in patients with echocardiographic findings of dilated and poorly contracting left ventricle and coexisting systemic hypertension. It is conceivable, in such cases, to classify the dilatation of the left ventricle as secondary and to suggest the hypothesis of a cause-effect relationship between therapy and normalization of left ventricular parameters with findings of left ventricular hypertrophy. Further studies are needed to clarify this phenomenon.

[Echocardiographic and color Doppler diagnosis in congenital aneurysm of the mitral-aortic intervalvular fibrous tissue]. / Diagnosi ecocardiografica e color Doppler di aneurisma congenito del tessuto fibroso intervalvolare mitro-aortico.

We describe the case of a 12-years-old boy, who had an echocardiogram for sports fitness. The echocardiographic image showed a small probably congenital aneurysm of the mitral-aortic intervalvular fibrosa. The diagnosis of this rare anomaly was made possible by the combination of bidimensional echocardiographic and Color Doppler information.

[Comparison of continuous wave Doppler and heart catheterization in the determination of the mean transvalvular gradient in mitral stenosis. A simultaneous beat to beat analysis]. / Confronto tra Doppler ad onda continua e cateterismo cardiaco nella determinazione del gradiente medio transvalvolare nella stenosi mitralica. Analisi contemporanea battito su battito.

Continuous wave Doppler echocardiography (CWD) is widely used in the assessment of pressure gradients in patients with valvular heart disease, utilizing the simplified Bernoulli equation. However determination of non-simultaneous mean pressure gradient (MG) in mitral stenosis (MS) from CWD recordings has often been described as being unsatisfactory. Therefore, the purpose of this study was to compare the estimates of trans-mitral MG derived from CWD with gradients measured simultaneously at cardiac catheterization (beat to beat analysis). We studied 3 patients (pts) with MS (1 man and 2 women, aged 55, 55 and 62 years respectively); one patient (pt) was in sinus rhythm and 2 were in atrial fibrillation. In each pt the trans-mitral flow velocity curve was obtained simultaneously with trans-mitral gradient measured directly at cardiac catheterization (cath). In this way it was possible to obtain a beat to beat correlation between Doppler and cath in 181 beats taken from the 3 pts. These beats were selected from a total number of 321 beats because of their excellent quality for analysis (74 beats were obtained from the first pt, 38 from the second pt and 69 from the third pt). Mean diastolic velocity, defined as the mean of maximal velocities throughout diastole, was obtained for each beat by planimetring the envelope of the spectral velocity profile. MG was calculated from mean velocity by applying the simplified Bernoulli equation (delta P = 4V2).(ABSTRACT TRUNCATED AT 250 WORDS)

Feasibility and variability of six methods for the echocardiographic and Doppler determination of cardiac output.

The feasibility and the intrinsic variability of six different methods of echocardiographic and Doppler flow determination of cardiac output were analysed in 34 healthy volunteers. Four were excluded because of poor quality echocardiograms. The mean (range) age of the remaining 30 (12 women, 18 men) was 21 years (13-36 years). Cardiac output was calculated by six methods as a product of echocardiographically determined cross sectional area of the aorta (apical and suprasternal views), pulmonary trunk, tricuspid annulus, and mitral annulus (circular and corrected for diastolic variations), and the flow velocity integral measured by Doppler. Cardiac output ranged from 2.79 to 6.56 1/min (4.45 (1.29) 1/min) (mean (SD)). The feasibility of the methods ranged from 87% (26 patients) for the aorta from the suprasternal notch to 100% (30 patients) for the mitral orifice corrected for diastolic variations and for the tricuspid valve. The corresponding results for all 34 individuals were 76% and 88% respectively. Three way analysis of variance was performed in the 23 healthy volunteers in whom all six methods were feasible. Interobserver and intraobserver interpretative variabilities were 6.8% and 5.9% respectively. The intrinsic variability of each single measurement of cardiac output, independently of the observer and the method used, was 25%. Provided the image was suitable for analysis echocardiographic and Doppler flow determination of cardiac output was feasible in most healthy volunteers. But there was significant intrinsic variability for each of different methods. A single value of cardiac output in an individual should be interpreted with caution.

[Normally functioning mitral prosthesis: visualization and characterization of the trans-valvular flow using color-coded Doppler]. / Protesi mitraliche normofunzionanti: visualizzazione e caratterizzazione del flusso transvalvolare mediante Doppler a codice di colori.

Color flow imaging (CFI) allows real time visualization of intracardiac and transvalvular blood flow, superimposed on two-dimensional echocardiographic images. Therefore it can be useful in the identification and characterization of spatial configuration of jets through valve prosthesis. The aim of this study was to define the transvalvular flow pattern of jet in 54 patients (pts) with mitral valve prosthesis which were functioning well. Thirty-six of these pts were females and 18 males; their ages ranged from 40 to 73 years, mean age: 58. Prosthetic mitral inflow was evaluated utilizing the parasternal long axis, apical long axis and apical 4 chamber views; in addition ("off axis") intermediate sections were used when needed. Adequate CFI for detailed frame by frame analysis was obtained in 50 pts (92%). Fourteen pts had biological prosthesis (9 Hancock, 4 Carpentier-Edwards, 1 Ionescu-Shiley). Thirty-six pts had mechanical prosthesis: 13 Björk-Shiley, 8 Starr-Edwards, 9 Sorin, 5 Lillehey-Kaster, 1 Smeloff-Cutter. Variable jet configurations were identified, which were related to the type of prosthetic valve. Bioprosthetic valve characteristically had a wide, homogeneous transvalvular flow, directed towards the interventricular septum. Björk-Shiley prosthesis presented typically a jet with two components. Trans-prosthetic flow was dependent on the spatial position of the prosthesis and on the orientation of the tilting disc. Thus, the main jet, coming from the major orifice, could be directed towards the apex, flowing parallel to the left ventricular postero-lateral wall while the jet coming from the minor orifice was thin and directed towards the interventricular septum.(ABSTRACT TRUNCATED AT 250 WORDS)

[Visualization and characterization of the transvalvular jet in mitral stenosis using color-coded Doppler]. / Visualizzazione e caratterizzazione del jet transvalvolare nella stenosi mitralica mediante Doppler a codice di colori.

Two-dimensional Color Doppler flow imaging is a new non-invasive technique which allows real-time visualization of intracardiac blood flow and provides informations about its direction, velocity and presence of turbulence. As a consequence the identification of jets configuration across stenotic valve orifices is now possible by Color flow imaging. This non invasive tool may be particularly helpful in patients with rheumatic mitral valve disease in whom distortion of mitral valve apparatus is often present, determining a non uniform and variable appearance of jets. Therefore the aim of this study was to describe our initial experience with color flow imaging in the visualization of transtenotic mitral jets in order to characterize different spatial configurations. We studied 45 patients with clinical and echocardiographic diagnosis of mitral stenosis. The mean age of these patients was 59 years (range from 36 to 72 years), 34 were women and 11 men. The different types of transmitral jets were characterized by real time and frame by frame analysis. The following characteristics of transmitral jets have been evaluated: A) appearance ("Candle flame", "Mushroom", "Scimitar"-shaped, "Double-jets"); B) direction (centrally directed or eccentric); C) extension into the left ventricle (basal, mid-ventricular and apical); D) persistence of turbulent flow during diastole (early-, mid-, late diastole). Mitral valve area was calculated from the velocity tracings obtained by continuous wave Doppler, applying the pressure half-time method. Color flow imaging of good quality for analysis was obtained in 41 of 45 patients (91%). In the other 4 patients the quality of color flow images was suboptimal however the direction and configuration of the jets could still be visualised.(ABSTRACT TRUNCATED AT 250 WORDS)

[Characterization of transmitral flow using color-coded Doppler in a case of left atrial myxoma]. / Caratterizzazione del flusso transmitralico mediante Doppler a codice di colori in un caso di mixoma atriale sinistro.

The authors describe the transmitral flow pattern by color flow imaging in a patient with left atrial myxoma. The usefulness of color Doppler relays in the identification of the eccentric direction of transmitral flow, possibly present in such situation.

[Study of the intracardiac flow by real-time bidimensional color-coded Doppler echocardiography. Preliminary experience]. / Studio dei flussi intracardiaci mediante ecocardiografia bidimensionale e doppler a codice di colori in tempo reale. Prime esperienze.

The new technique of real-time two-dimensional color Doppler echocardiography has been recently developed to allow visualization of the blood flow inside the cardiac chambers. The blood flow informations are color coded and displayed in real-time into the two-dimensional echocardiographic images of the cardiac structures. The flow informations which are given are velocity, direction and variance, calculated from the Doppler signals obtained from all the sample points. Flow directed toward the transducer is coded in red; flow away from the transducer is coded in blue, while the echoes from the cardiac structures are imaged in gray scale. The magnitude of the velocity of flow is represented by the brightness of the color, with an 8-steps scale of brightness, beginning from the lowest grade, which is not colored on the screen. To represent the velocity spectrum variance, green is added to each color in proportion to the extent of turbulence. We report our preliminary experience with this technique in 91 subjects by using an Aloka SSD 880 commercial equipment (age range 18 days-82 years): 5 were normal, 15 had cardiomyopathy, 21 had congenital, 40 valvular, 6 ischemic and 4 other forms of heart disease. Color display of intracavitary flow allowed to identify normal and abnormal patterns. Valvular regurgitation and abnormal intracavitary shunts were easy to identify, suggesting the possibility of a semiquantitative assessment of the lesions. The possibility of a quantitative approach should be further investigated in the future.(ABSTRACT TRUNCATED AT 250 WORDS)

[Possibilities and difficulties of differential diagnosis by 2-dimensional echocardiography of mobile masses inside the right atrium. Apropos of a case]. / Possibilità e difficoltà di diagnostica differenziale mediante ecocardiografia bidimensionale di masse mobili all'interno dell'atrio destro. A proposito di un caso.

A peculiar case of mobile right atrial mass thrombotic in origin identified by two-dimensional echocardiography is reported. By the characteristics of the mass and the negative history for SBE and malignant neoplasm, the possibilities of tricuspid vegetations or infiltration by an extracardiac tumor could be reasonably ruled out. On the other hand, a myxomatous mass could not be excluded in this case. The thrombotic nature of the mass was recognized at autopsy. The possibility to identify by two-dimensional echocardiography right atrial masses together with the difficulties in certain particular cases to recognize their nature are discussed.