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R De Simone

Publications and source records attributed to R De Simone.

At least 37 records · Page 2Linked to original sources

Three-dimensional color Doppler flow reconstruction and its clinical applications.

The visualization and quantification of intracardiac blood flow have always been a challenging task for the cardiologist. The advent of color Doppler flow imaging substantially enhanced the clinical diagnosis of heart valve disease. Three-dimensional (3-D) color Doppler, a new diagnostic procedure, refines the diagnostic value of color Doppler by providing unique spatial and temporal information about the actual extension, direction, origin, and size of intracardiac flows. Here, we describe the procedure for 3-D color Doppler reconstruction of intracardiac blood flow velocities and reveal the varied findings in different heart pathologies that cause blood flow disturbances. An automated procedure for the segmentation of turbulent and laminar flows, which allows for the measurement of mitral regurgitant jet volumes, is one of the first 3-D quantitative approaches to the clinical assessment of mitral valve regurgitation. The major technical advances of this procedure include the direct use of digital color Doppler velocity data and an automatic voxel count of the turbulent jet flows. Three-dimensional color Doppler not only can disclose the spatial complex geometry of intracardiac blood flow disturbances but also can quantitatively assess the severity of mitral valve regurgitation.

Aortic Valve Stenosis↗

Opposite effects of interferon-gamma and prostaglandin E2 on tumor necrosis factor and interleukin-10 production in microglia: a regulatory loop controlling microglia pro- and anti-inflammatory activities.

Following brain injury, microglial cells produce pro- and anti-inflammatory cytokines, such as tumor necrosis factor (TNF) and interleukin-10 (IL-10). IL-10 provides an efficient autocrine mechanism for controlling microglia activation. To elucidate the mechanisms that regulate the cytokine profile of microglia, we examined the effects of several immunomodulators on IL-10 and TNF production by cultured mouse microglia. Lipopolysaccharide (LPS) was the only inducer of IL-10 and TNF gene expression and secretion. The T helper 1-type cytokine interferon-gamma (IFN-gamma) induced TNF transcripts, but not TNF secretion, and suppressed LPS-induced IL-10 mRNA and secretion by microglia. Opposite to IFN-gamma, the lipid mediator prostaglandin E2 (PGE2) enhanced the LPS-induced production of IL-10 and inhibited that of TNF. The effects of PGE2 on cytokine gene expression and secretion were antagonized by IFN-gamma. Agents that increase cAMP levels mimicked the action of PGE2 on cytokine secretion, indicating the involvement of cAMP-coupled prostaglandin receptors. In conclusion, IFN-gamma and PGE2, two mediators released at inflammatory sites, differentially regulate the production of a proinflammatory and an anti-inflammatory cytokine in microglia. We suggest that the activity and role of microglia in the damaged CNS could be finely tuned by the local concentration ratio of these mediators.

Animals↗

Assessment of mitral regurgitant jets by three-dimensional color Doppler.

BACKGROUND: Color Doppler echocardiography is a standard technique for assessing mitral regurgitation before and after mitral valvuloplasty. Mitral valve prolapse produces complex eccentric jet flows that cannot be visualized and measured by two-dimensional color Doppler echocardiography. The aim of this study was to evaluate the clinical impact of three-dimensional color Doppler echocardiography, a new technique developed at our institution, for assessing mitral regurgitation. METHODS: Forty-five patients with mitral regurgitation underwent intraoperative transesophageal echocardiography and three-dimensional Doppler data acquisition. The grade of mitral regurgitation was assessed by angiography. The jet areas were calculated by planimetry from conventional color Doppler; the jet volumes were obtained by three-dimensional Doppler data. RESULTS: New patterns of mitral regurgitant flows were recognized according to the origin, direction, and spatial spreading into the left atrium. Conventional jet areas failed to separate the groups of patients with different degrees of regurgitation, whereas the jet volumes were able to divide patients with different regurgitation grades. No significant correlation was found between jet area and angiographic grading (r = 0.63, p = NS). Jet volumes were significantly correlated to angiography (r = 0.89, p < 0.001). CONCLUSIONS: Three-dimensional color Doppler echocardiography revealed new patterns of regurgitant flow and allowed a more accurate semiquantitative assessment of complex asymmetrical regurgitant jets.

Blood Flow Velocity↗

Three-dimensional color Doppler: a clinical study in patients with mitral regurgitation.

OBJECTIVES: The purpose of this study was to assess the clinical feasibility of three-dimensional (3D) reconstruction of color Doppler signals in patients with mitral regurgitation. BACKGROUND: Two-dimensional (2D) color Doppler has limited value in visualizing and quantifying asymmetric mitral regurgitation. Clinical studies on 3D reconstruction of Doppler signals in original color coding have not yet been performed in patients. We have developed a new procedure for 3D reconstruction of color Doppler. METHODS: We studied 58 patients by transesophageal 3D echocardiography. The jet area was assessed by planimetry and the jet volumes by 3D Doppler. The regurgitant fractions, the volumes, and the angiographic degree of mitral regurgitation were assessed in 28 patients with central jets and compared with those of 30 patients with eccentric jets. RESULTS: In all patients, jet areas and jet volumes significantly correlated with the angiographic grading (r = 0.73 and r = 0.90), the regurgitant fraction (r = 0.68 and r = 0.80) and the regurgitant volume (r = 0.66 and r = 0.90). In patients with central jets, significant correlations were found between jet area and angiography (r = 0.86), regurgitant fraction (r = 0.64) and regurgitant volume (r = 0.78). No significant correlations were found between jet area and angiography (r = 0.53), regurgitant fraction (r = 0.52) and regurgitant volume (r = 0.53) in the group of patients with eccentric jets. In contrast, jet volumes significantly correlated with angiography (r = 0.90), regurgitant fraction (r = 0.75) and regurgitant volume (r = 0.88) in the group of patients with eccentric jets. CONCLUSIONS: Three-dimensional Doppler revealed new images of the complex jet geometry. In addition, jet volumes, assessed by an automated voxel count, independent of manual planimetry or subjective estimation, showed that 3D Doppler is also capable of quantifying asymmetric jets.

Adult↗

Three-dimensional color Doppler: a new approach for quantitative assessment of mitral regurgitant jets.

Color Doppler echocardiography does not provide adequate information about the severity of mitral regurgitation in patients with eccentric mitral regurgitation. We have developed a new procedure for 3-dimensional (3D) color Doppler reconstruction and for segmentation of regurgitant jets. The volume of regurgitant jets was compared with jet area in 63 patients with mitral regurgitation. Mitral regurgitation was assessed by angiography, regurgitant fraction and volume by pulsed Doppler, JA by planimetry, and JV by 3-dimensional Doppler. Twenty-eight patients with central jets were compared with 35 patients with eccentric jets. In the patients with eccentric jets, JV showed significant correlations with regurgitant volume (r = 0.90; P <.01) and regurgitant fraction (r = 0.76; P < .01) and was able to separate groups with different degrees of mitral regurgitation (P <.01). Three-dimensional Doppler revealed origin, direction, and spatial spreading of complex jet geometry. JV, a new parameter of mitral regurgitation, was also capable of quantifying asymmetrical jets.

Echocardiography, Doppler, Color↗

Three-dimensional color Doppler for assessing mitral regurgitation during valvuloplasty.

OBJECTIVE: Transesophageal color Doppler (or 2D Doppler) is the most widely used technique for intraoperative assessment of mitral valve repair. However, the most severe mitral regurgitations produce eccentric jet flows which cannot be assessed by 2D imaging. Up to now the indications for surgical intervention and intraoperative decisions after valve repair have been based on 2D Doppler examinations. Aim of this study was to compare conventional 2D Doppler to three-dimensional (3D) Doppler for assessing residual regurgitation in patients after mitral valvuloplasty. METHODS: Twenty-four patients were referred to surgery for mitral valve repair. They underwent transesophageal echocardiography and 3D data acquisition during mitral valve reconstruction. Conventional assessment of mitral valve regurgitation, measured by color Doppler jet area, was compared to the volume of regurgitant jets obtained by 3D Doppler. Regurgitant volume and fraction were measured by pulsed Doppler and two-dimensional echocardiography. The 3D reconstructions of color Doppler data were accomplished by means of the 'Heidelberg Raytracing Algorithm' developed at our institution. RESULTS: The jet areas did not show any significant correlation to the regurgitant fraction (r = 45; P = NS) or regurgitant volumes (r = 0.40; P = NS). In contrast the jet volumes correlated significantly to regurgitant fraction (r = 0.71; P < 0.01) and regurgitant volume (r = 0.85; P < 0.01). The reproducibility analysis of repeated jet volume and jet area measurements also showed that the parameter jet volume has a lower variability and higher agreement of repeated measurements than jet area. CONCLUSIONS: Three-dimensional color Doppler flow imaging revealed the complex geometry of eccentric regurgitant jets and showed that the assessment of mitral regurgitation, based on conventional 2D Doppler, can be misleading. This new technique has a great potential for becoming a reference method for assessing mitral valve repair.

Blood Flow Velocity↗

Three-dimensional Doppler. Techniques and clinical applications.

AIMS: Colour Doppler is the most widely used technique for assessing valve disease, but eccentric regurgitant jets cannot be visualized and measured by conventional 2D techniques. We have developed a new procedure for three-dimensional (3D) reconstruction of colour Doppler signals. METHODS AND RESULTS: Fifty patients with mitral regurgitation underwent transoesophageal echocardiography and 3D acquisition. The severity of mitral regurgitation was assessed by angiography and the regurgitant volumes were measured by pulsed Doppler. The jet areas were calculated by planimetry from conventional colour Doppler; the jet volumes were obtained by 3D Doppler. A higher degree of mitral regurgitation was found in the patients with eccentric jets. While jet areas showed poor correlation with regurgitant volumes (r = 0.61), jet volumes correlated significantly with regurgitant volumes (r = 0.93; P < 0.001). While jet areas failed to identify patients with different grades of regurgitation, jet volumes could so discriminate. CONCLUSIONS: 3D Doppler revealed new patterns of regurgitant flow and allowed a more accurate semiquantitative assessment of complex asymmetrical regurgitant jets. Three-dimensional colour Doppler has a great potential for becoming a reference method for the assessment of patients with heart valve disease.

Adult↗

A new diagnostic procedure for assessing intracardiac flow disturbances in patients with heart valve disease.

BACKGROUND: Until now no diagnostic technique was available for the three-dimensional (3D) study of intracardiac blood flow abnormalities in patients with heart valve disease. 3D color Doppler is a new diagnostic technique first developed at our institution. METHODS: The 3D reconstructions of the blood flow velocity data have been obtained from conventional multiplanar transesophageal or transthoracic Doppler echocardiographic examinations. We analyzed 111 reconstructions of color Doppler data obtained from 85 patients with different heart valve diseases who underwent intraoperative transesophageal echocardiography. Sixty-nine patients had a significant mitral regurgitation, 7 mitral stenosis, 9 aortic regurgitation, 12 aortic stenosis, 14 tricuspid regurgitation. Three patients had pulmonary regurgitation associated with mitral valve disease. RESULTS: 3D color Doppler disclosed the complex spatial spreading of the blood flow abnormalities caused by heart valve disease. New patterns of intracardiac blood flow disturbances could be observed and classified. CONCLUSIONS: This paper shows the first clinical applications of 3D color Doppler in patients with heart valve disease. The new insights derived from the 3D study of intracardiac blood flow dynamics revealed a great impact of this technique on the clinical management of patients with heart valve disease.

Coronary Circulation↗

Elevated levels of lipoprotein (a) in patients suffering from myocardial infarction with carotid atherosclerotic lesions.

The aim of the present study was to evaluate metabolic, coagulation and fibrinolytic parameters in 45 patients [31 men, 14 women, aged 56.5 +/- 3.5 years (mean +/- SD)] who had suffered myocardial infarction more than 6 months earlier, with or without carotid atherosclerotic lesions. After the extracranial carotid arteries had been evaluated using a B-mode Duplex scanning system, patients were subdivided into two groups: group 1 (n = 20) with carotid plaques or measurable intima-media thickness; and group 2 (n = 25) without carotid plaques or measurable intima-media thickness. Twenty-two age- and sex-matched subjects were recruited as controls (group 3). Groups 1 and 2 displayed significantly higher levels of total cholesterol, apolipoprotein B, human autoantibodies against oxidised low-density lipoprotein and the c fraction of the third component system, and significantly lower levels of high-density lipoprotein cholesterol and apolipoprotein A1 than group 3. However, serum levels of triglyceride and lipoprotein (a) were significantly higher in group 1 than in the control group. Moreover, groups 1 and 2 displayed significantly higher levels of factor VII, fibrinogen, fragment 1+2, thrombin-antithrombin complex and plasminogen activator inhibitor after venous occlusion, and significantly lower levels of tissue-type plasminogen activator after venous occlusion than group 3. Significantly higher levels of tissue-type plasminogen activator and plasminogen activator inhibitor before venous occlusion were observed in groups 1 and 2 and significantly lower levels of antithrombin III, protein C and protein S were observed in group 1 compared with the controls. Patients were also analysed according to levels of lipoprotein (a). The lowest levels of tissue-type plasminogen activator after venous occlusion and the highest levels fragment 1 + 2, the c fraction of the third component system, and plasminogen activator inhibitor after venous occlusion were observed in patients with the highest levels of lipoprotein (a). Our data demonstrate an activation of coagulation and deficient fibrinolysis in survivors of myocardial infarction, particularly in those with associated carotid atherosclerotic lesions. We speculate that this thrombophilic state may play a key role in the pathogenesis of atherosclerotic vascular disease and thromboembolic complications.

Apolipoproteins↗

Interferon gamma gene expression in rat central nervous system glial cells.

The expression of interferon gamma (TFN-gamma) mRNA in purified cultures of glial cells and leptomeningeal fibroblasts from the neonatal rat brain was analysed using semi-quantitative reverse transcriptase-polymerase chain reaction. IFN-gamma specific transcripts were clearly detected in rat astrocytes and were upregulated after treatment with IFN-gamma itself or cycloheximide. In microglial cells, IFN-gamma transcripts were barely detectable in basal conditions and were upregulated by lipopolysaccharide and, to a lesser extent, by IFN-gamma or cycloheximide. IFN-gamma mRNA was neither detected not inducible in oligodendrocytes and leptomeningeal cells. The demonstration that IFN-gamma is expressed in astrocytes and microglia widens the putative role of these cells in local immunoregulation and antiviral responses.

Animals↗

Interferon-gamma in progression to chronic demyelination and neurological deficit following acute EAE.

The cytokine interferon-gamma (IFNgamma) is implicated in the induction of acute CNS inflammation, but it is less clear what role if any IFNgamma plays in progression to chronic demyelination and neurological deficit. To address this issue, we have expressed IFNgamma in myelinating oligodendrocytes of transgenic mice. MHC I immunostaining and iNOS mRNA were upregulated in their CNS, but such transgenic mice showed no spontaneous CNS inflammation or demyelination, and the incidence, severity, and histopathology of experimental autoimmune encephalomyelitis (EAE) were similar to nontransgenic controls. In contrast to control mice, which remit from EAE with resolution of glial reactivity and leukocytic infiltration, transgenics showed chronic neurological deficits. While activated microglia/macrophages persisted in demyelinating lesions for over 100 days, CD4(+) T lymphocytes were no longer present in CNS. IFNgamma therefore may play a role in chronic demyelination and long-term disability following the induction of demyelinating disease. Because IFNgamma may have neural as well as immune-infiltrating origins, these findings generate a new perspective on its role in the CNS.

Animals↗

Changes in cerebral blood flow velocities during childhood absence seizures.

A simultaneous recording of mean flow velocity in the right middle cerebral artery by transcranial Doppler ultrasonography and electroencephalographic activity was performed in 5 children with multiple daily typical absence seizures. Twenty-eight absence episodes were recorded. Mean flow velocity increased gradually a few seconds before the clinical and electroencephalographic manifestations of each seizure and reached the maximum values (range of increase: 25.5-42.8% with respect to baseline) within 2-3 seconds from their onset. This increase was then followed by a fast reduction in flow velocity, with the lowest levels (range of decrease: 30.8-44.0% with respect to baseline) recorded within 4-6 seconds from the end of each absence seizure. These findings suggest that changes in cerebral blood flow and activity are quite complex during absence seizures and that they do not fully correlate with clinical and electroencephalographic manifestations.

Analysis of Variance↗

Tricuspid valve reconstruction, a treatment option in acute endocarditis.

Tricuspid valve endocardititis is treated surgically by total valve excision or valve replacement. Both procedures are controversial with regard to the hemodynamic consequences and to the long-term prognosis. In the following, results of tricuspid valve repair in acute infective endocarditis are reported and discussed as an additional treatment option. Between January 1988 and December 1993, 118 patients were operated on for acute valve endocarditis at our institution. Eleven of these patients had tricuspid valve endocarditis, isolated (n = 7) or combined with endocarditis of a left-sided valve (n = 4). In the cases with isolated tricuspid valve endocarditis, the indication for surgery was intractable infection in six and hemodynamically relevant tricuspid insufficiency in one out of seven patients. In all patients with associated left-sided endocarditis, the indication was hemodynamic deterioration. In eight patients the tricuspid valve endocarditis was treated as follows: debridement, vegectomy, patch reconstruction of the cusps, reducing the cusps to two. In three patients reconstruction was not possible because of extensive involvement of all parts of the valve, including the valve ring and the papillary muscles. In these patients primary valve replacement (n = 1) or valve excision with secondary replacement (n = 2) was performed. In four patients tricuspid reconstruction was combined with mitral (n = 1), aortic (n = 1) or double valve replacement (n = 2). Postoperatively, signs of infection vanished in all surviving patients (n = 10) and tricuspid valve endocarditis healed without recurrences. Implanted prosthetic material did not lead to recurrent infection. One patient died early postoperatively after valve excision, in septic shock and multi-organ failure. In seven patients late echocardiographic follow-up showed tricuspid regurgitation grade 0 in three patients, I in two, II in one and III in one. Our results suggest that valve repair is a reasonable treatment option for tricuspid valve endocarditis in all cases with localized infection of the valve. Only if extensive valve destruction excludes valve repair, would we now favor primary valve replacement over simple valvulectomy. In all other cases primary valve reconstruction is the treatment of choice for tricuspid valve endocarditis, if surgery is indicated.

Acute Disease↗

Cytokine-regulated expression of platelet-derived growth factor gene and protein in cultured human astrocytes.

To elucidate mechanisms regulating the production of platelet-derived growth factor (PDGF) in the CNS, we analyzed the influence of a panel of cytokines on PDGF mRNA and protein levels in astrocyte-enriched cultures from the human embryonic brain and spinal cord. Using a specific ELISA, PDGF, AB protein was detected in serum-free astrocyte supernatants and its levels were significantly increased after treatment of the cultures with transforming growth factor-beta 1 (TGF-beta 1) or tumor necrosis factor-alpha (TNF-alpha); the largest increase was detected after combined treatment with the two cytokines. Interleukin-1beta (IL-1beta) by itself had little or no effect but synergized with TGF-beta 1 in enhancing PDGF AB production. Supernatants from human astrocyte cultures stimulated the proliferation of rat oligodendrocyte progenitors, and most of the mitogenic activity could be accounted for by PDGF. By northern blot analysis, both PDGF A- and PDGF B- chains mRNAs were detected in untreated astrocytes. PDGF B-chain mRNA levels were increased by TGF-beta 1, TNF-alpha, TNF-alpha/TGF-beta, or IL-1-beta/TGF-beta 1, whereas PDGF A-chain mRNA levels were not consistently affected by cytokine treatments. These in vitro data indicate that TGF-beta 1, TNF-alpha, and IL-1 beta are able to stimulate astrocyte PDGF production. This cytokine network could play a role in CNS development and repair after injury or inflammation.

Astrocytes↗

mRNA for NGF and p75 in the central nervous system of rats affected by experimental allergic encephalomyelitis.

In this study we measured the concentration of nerve growth factor (NGF) and the expression of NGF and the low affinity NGF-receptor (NGF-r) mRNA in the central nervous system (CNS) of rats affected by experimental allergic encephalomyelitis (EAE) during the acute phase of the disease. Significant levels of NGF protein were found in thalamus and cortex on day 13 post-immunization. Molecular analysis of the NGF gene expression and of its NGF-r revealed that they were enhanced in several regions of the CNS of EAE rats when compared with untreated animals. These results suggest a functional link between local NGF synthesis and this autoimmune inflammatory disease.

Animals↗

Treatment of dilated cardiomyopathy with dynamic cardiomyoplasty: the Heidelberg experience.

BACKGROUND: Data concerning the efficacy of dynamic cardiomyoplasty are still inconsistent, especially in terms of improvement of left ventricular function. METHODS: Between August 1990 and February 1994, eight isolated cardiomyoplasty procedures were performed in patients with cardiomyopathy (ejection fraction, 0.14 to 0.32; New York Heart Association class III) and contraindications to heart transplantation. RESULTS: Follow-up was 41.1 +/- 14.1 months. One patient died 2 months and another 3 years after operation. Considerable symptomatic improvement was found in 6 of 7 patients, 3 of whom went back to work. One patient with severe pulmonary hypertension exhibited no improvement. Mean New York Heart Association-class decreased from 3.0 to 1.9 (p < 0.001). Echocardiography showed an increase in fractional shortening and in peak aortic flow velocity in all patients. Left ventricular ejection fraction increased from 0.21 +/- 0.05 to 0.38 +/- 0.16 (n = 7, p < 0.015) at 1 year, to 0.37 +/- 0.18 (n = 6, p < 0.05) at 2 years, and to 0.36 +/- 0.19 (n = 5, not significant) at 3 years. Pulmonary artery pressure tended to decrease over time. No significant change in exercise level or maximal oxygen consumption during treadmill testing was observed. CONCLUSIONS: Our preliminary results show that patients may exhibit an impressive clinical improvement after cardiomyoplasty, with only moderate changes in objective hemodynamic indices. We do not consider cardiomyoplasty an alternative to heart transplantation, but reserve it for patients with contraindications to heart transplantation.

Cardiomyopathy, Dilated↗

Atrioventricular valve insufficiency and atrial geometry after orthotopic heart transplantation.

BACKGROUND: The etiology of tricuspid and mitral valve regurgitation (TR and MR) after heart transplantation is still controversial. METHODS: We studied 25 patients undergoing transplantation and intraoperative transesophageal echocardiography to evaluate the incidence, the degree, and the cause of TR and MR. The degree of valve regurgitation was assessed by color Doppler echocardiography. Cross-sectional areas of the recipient (R) and donor (D) portions of the atria and their ratio (R/D) were measured to assess the distortion of atrial geometry. Tricuspid and mitral valve annuli, their systolic shortening, and hemodynamic indices were measured preoperatively and perioperatively. RESULTS: Tricuspid valve regurgitation was found in 21 of 25 patients (84%) and MR in 12 of 25 (48%). The degree of MR was mild, whereas TR was mild to moderate. Mitral valve regurgitation did not show any correlation with the studied indices; TR showed no correlation with the hemodynamic indices but a significant correlation with R/D ratio (r = 0.90; standard error of the estimate = 0.2). An inverse correlation was found between the degree of TR and systolic shortening of tricuspid annulus (r = -0.88; standard error of the estimate = 0.03) and between R/D ratio and systolic shortening of tricuspid annulus (r = -0.85; standard error of the estimate = 0.04). CONCLUSIONS: Tricuspid valve regurgitation has a higher incidence than MR and occurs immediately after transplantation; MR is mild and correlates with neither hemodynamic indices nor atrial distortion. An increased R/D ratio, and hence distortion of right atrial geometry, may lead to a reduction in systolic annulus shortening, which in turn causes TR. Surgical attempts to reduce the R/D ratio may decrease the incidence and the degree of TR after heart transplantation.

Echocardiography, Doppler, Color↗