Lack of bilirubin removal during dialysis without an impact on creatinine clearance.
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Biomedical subjects
Publications and source records attributed to G Pelle.
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Interactions between the endothelium and erythrocytes may contribute to the vascular complications of sickle cell disease (SCD). Endothelium-derived nitric oxide (NO) plays a major role in the regulation of vasomotor tone in response to wall shear stress (WSS) variations and pharmacologic stimuli. However, little is known about endothelial NO production in patients with steady-state SCD. We investigated endothelial NO production in response to flow or vasoactive agonists in 16 homozygous patients with steady-state SCD and 15 controls. Flow-mediated dilation (FMD), arterial diameter changes in response to 100% oxygen inhalation, blood viscosity, and calculated WSS were determined in all patients and controls. At baseline, WSS was higher in SCD patients than in controls, whereas arterial diameter was similar. In patients with SCD, FMD was impaired (1.73% +/- 0.44% vs 3.97% +/- 0.24% in the controls, P <.001) and vasoconstriction in response to 100% oxygen was abolished. Using venous occlusion plethysmography, forearm blood flow (FBF) was evaluated in response to acetylcholine, nitro-monomethyl-L-arginine (L-NMMA), and sodium nitroprusside (SNP) in subgroups of 9 controls and 7 patients with SCD. Acetylcholine induced a significantly greater FBF increase in the patients (9.7 +/- 2.9 mL/min/100 mL of forearm volume vs 2.5 +/- 1.5 mL/min/100 mL in the controls, P <.001), whereas responses to L-NMMA and SNP were similar. These results suggest that endothelial dysfunction may prevent the arterial diameter of patients with SCD from adapting to chronic or acute shear stress elevations. This may contribute to the pathophysiology of vaso-occlusive crisis in patients with SCD.
This study was performed in order to quantitate structural coronary plaque modifications after balloon angioplasty and stenting and to evaluate the impact of plaque morphology on the mechanisms of lumen enlargement during angioplasty. Plaque morphology was studied by computer-aided analysis of 60 cross-sectional intravascular ultrasound (IVUS) images of the target lesion in 20 patients undergoing percutaneous coronary angioplasty. Based on a computer-aided video densitometry classification of plaque morphology, three groups of plaques were defined based on the slope value of a fifth polynomial regression of the plaque gray-level distribution. In groups A and B, balloon angioplasty provided significant increases in lumen area (P < 0.0001) and vessel area (P < 0.05) without a reduction in plaque area; neither parameter increased in group C. In group A, stenting was associated with an additional lumen enlargement (P < 0.0001) due to plaque reduction (P < 0.05). In groups B and C, stenting further increased lumen area (P < 0.0001) by improving vessel area (P < 0.001) but without plaque reduction. Balloon angioplasty and stenting provided a significant decrease in plaque area in group A as compared to groups B (P < 0.05) and C (P < 0.01). Finally, vessel area improvement was greater in group B than in groups A (P < 0.01) and C (P < 0.05). The mechanisms underlying lumen enlargement after coronary angioplasty are highly dependent on plaque morphology as defined by an IVUS computer-aided analysis and may differ between balloon angioplasty and stenting.
The results of an observational multicenter angioplasty study suggested that stenting decisions may be facilitated by physiologic data. The purpose of this study was to evaluate the early and long-term clinical and angiographic outcome of prospective physiologically guided provisional stenting. Coronary angioplasty using a Doppler-tipped angioplasty guidewire was performed in 68 patients. The provisional stent strategy dictated that balloon angioplasty was to be continued until a coronary flow reserve was >/= 2.2 with a residual diameter stenosis by quantitative coronary angiography < 35%. Repeat coronary angiography was obtained at 6 months. Based on the study criteria, 32/68 patients (47%) received a stent. Compared to the stent group, the angioplasty alone group had higher postprocedural stenosis (23% +/- 13% vs. 13% +/- 10%; P < 0. 05) and lower coronary vasodilatory reserve (2.3 +/- 0.4 vs. 2.6 +/- 0.7; P < 0.05). At follow-up (6.0 +/- 1.5 months), the angiographic restenosis rate was 39% in the angioplasty group and 35% in the stent groups (P = NS). Adverse cardiac events (unstable angina, target lesion revascularization, myocardial infarction, death) occurred in 19% and 18% (P = NS) of the angioplasty and stent patients, respectively. A prospective application of a physiologically guided provisional stent strategy for coronary angioplasty indicated that stent implantation may be required in approximately 50% of patients, an approach that produces similar clinical and angiographic long-term outcomes for stenting and guided angioplasty. These data support a role of coronary physiology as an adjunct in conducting an angioplasty procedure without obligatory stenting.
Actinomyces hordeovulneris was isolated from the lesions of chronic pyogranulomatous pleuritis and pericarditis of one of three dogs showing similar symptoms. The parietal pleura and the pericardium were thickened and covered with fine short threads of angiofibroblastic tissue. About 500-1000 ml of reddish purulent exudate in the thorax of all three dogs contained large numbers of rice-grain-sized, soft, yellowish-white granules ("sulphur granules"). These granules had a central core of branching filaments of gram-positive bacteria embedded in thick granulation tissue. The parietal pleura, the mediastinal pleura and the pericardium were infiltrated mainly with neutrophils, and to a lesser extent with lymphocytes and plasma cells. A small number of eosinophils and giant cells was also observed. Large numbers of pyogranulomas embedded in the granulation tissue were composed of a core of necrotized granulation tissue, mixed with clusters of gram-positive branching bacteria, surrounded by an area of intact and degenerating neutrophils and lymphocytes. Bacteria were detected in the lesions by Brown-Brenn staining and were isolated from one of the affected animals. The isolated bacteria were identified as A. hordeovulneris. This was the first isolation of A. hordeovulneris in Hungary.
Flow-mediated vasodilation (FMD) of human blood vessels is essential to adaptation and regulation of peripheral blood flow, and is mediated by endogenously produced nitric oxide. Endothelial function is impaired in many pathologic states, especially in coronary heart disease. We questioned in this study whether exogenous nitric oxide (NO) would restore endothelial dysfunction in peripheral arteries of patients with coronary artery disease (CAD). In a randomized double-blinded case-control assay, we used computerized A-mode ultrasonography to measure diastolic diameters of the brachial artery before and after hyperemia in two groups of 10 patients with CAD. Each group received orally either placebo or 12 mg molsidomine a day for 48 h. In the molsidomine group, FMD was improved with a 60% increase after the first intake of molsidomine, and the same trend was observed after the last intake, although less pronounced. Significant increase in diastolic diameter was observed after the last molsidomine intake, but not after the first one. Thus molsidomine has an early positive effect on FMD in addition to a delayed vasodilator effect. Improvement of endothelial dysfunction by molsidomine in patients with CAD may uncover new therapeutic perceptive in the use of nitrovasodilators.
Intra-coronary ultrasonography (ICV) is a technique for in vivo study of the different layers of the arterial wall, the site of atherosclerosis. A qualitative analysis of the composition of the plaque can predict its potential evolutivity (chronic with slow progression or at risk of rupture and causing acute thrombosis) and its response to different types of angioplasty, which could eventually become and essential factor in the choice of appropriate therapeutic strategy. Analysis of the results of B mode ultrasonic scanning has provided correlations with the histological composition of the arterial wall, validating the method and opening up the field of tissue characterisation which hitherto had been limited by the absence of sufficiently reliable, accurate and reproducible quantitative parameters. Magnetic resonance imaging (MRI) is a complementary, non-invasive tool for tissue analysis because its sensitivity to the biophysical and biochemical properties of tissues which makes it a promising method of morphological and functional imaging. Other methods of imaging atheromatous plaques include angioscopy and optic coherence tomography which have also contributed to the improvement in our knowledge of atherosclerosis. These methods of imaging which are slowly overcoming their limitations provide documents which ressemble more and more the histological appearances. Intracoronary ultrasonography is the most promising method and raises hopes that one day we shall be able to predict the outcome and anticipate the risk of rupture of atherosclerotic plaques.
Small pressure transducer and Doppler quartz placed at the tip of angioplasty guide wire give the opportunity to measure coronary flow physiology parameters, the physiopathologic impact of an epicardic coronary stenosis and the efficacy of its treatment. This gives the opportunity to over ride the coronary imaging limitations. Doppler and pressure investigate a different and complementary aspect of the pressure-flow relation and may be used together in some special cases. Myocardial fractional flow reserve (FFRmyo) and relative coronary reserve concepts allow to evaluate patients with heterogeneous coronary reserve. Clinical application field is very broad and can be applied to each step of coronary angioplasty from the evaluation of intermediate lesions and the indication of angioplasty to the guidance of the procedure to the evaluation of the result, through the stenting indication and the stent placement optimization. Numerous studies has emphasized the role of physiologic coronary assessment in the cathlab. The time and economic gain of such an attitude has to be confirmed by future trials but it is clear now that it is not possible to continue to take decision on the sol visual aspect of a lesion.
Intracoronary ultrasound allows in vivo examination of the various layers of the wall of arteries affected by atherosclerosis. Its use in the catheterisation laboratory has therefore allowed better understanding of the mechanism of the action of the various angioplasty procedures, allowing better guidance of the indications and better control of these techniques. It also helps to guide these procedures, thereby facilitating an optimal immediate result, which determines the long-term outcome. The characteristics of intracoronary ultrasound (high resolution, proximity of the arterial wall, echogenicity of constituents of the plaque) make it the instrument of choice to study the composition and structure of the plaque, which determine the clinical presentation and active potential, especially the risk of complications (rupture). The development of image and crude acoustic signal processing techniques have improved the performance of the analysis of these documents and raise hopes of one day being able to predict and anticipate plaque rupture.
OBJECTIVES: The aim of this study was to assess the effects of ischemia on diastolic function by analyzing flow propagation velocity with color M-mode Doppler echocardigraphy. BACKGROUND: Color M-mode Doppler echocardiography has been proposed as a method of assessing left ventricular filling. METHODS: Color M-mode Doppler echocardiography and measurement of hemodynamic data were performed simultaneously at baseline and during angioplasty-induced ischemia. Tau was compared with flow propagation velocity. Late diastolic indexes, left ventricular pressure and flow cessation time were also investigated. RESULTS: During ischemia, left ventricular relaxation rate (tau) increased, whereas flow propagation velocity decreased, from (mean +/- SD) 46.8 +/- 10 ms to 72.6 +/- 18.3 ms and from 59.8 +/- 15.8 cm/s to 30 +/- 8 cm/s, respectively (all p < 0.0001). The maximal slowing of flow propagation velocity was observed 20 to 30 s after the beginning of the inflation, coexisting with a notch on the ascending limb of the negative rate of rise of the left ventricular pressure (dP/dt) curve. Flow propagation velocity was correlated with tau both at baseline (r = 0.53, p < 0.05) and during inflation (r = 0.53, p < 0.03). Left ventricular end-diastolic pressure increased during ischemia from 13.5 +/- 8 mm Hg at baseline to 27.5 +/- 7 mm Hg, while a premature cessation of the entering flow occurred -13.8 +/- 23 ms before the next Q wave onset, compared with 4.5 +/- 19.6 ms after the Q wave onset at baseline (all p < 0.0001). CONCLUSIONS: The analysis of flow propagation velocity showed that early filling is highly dependent on left ventricular relaxation rate, particularly through the phenomenon of asynchrony. During ischemia, the premature cessation of late filling is associated with increased diastolic pressures.
OBJECTIVES: The purpose of the present study was to assess whether brief, repeated coronary artery occlusions during balloon angioplasty induce a myocardial ischemic protective effect. BACKGROUND: In animals, brief coronary artery occlusions preceding a more prolonged occlusion result in reduced infarct size. Whether myocardial protection against ischemia could also occur in humans during angioplasty remains controversial. METHODS: Thirteen patients with a proximal left anterior descending coronary artery stenosis with no angiographic collateral circulation underwent percutaneous transluminal coronary artery balloon angioplasty. Three 120-s balloon inflations separated by a 5-min equilibration period were performed. For each inflation, intracoronary ST segment modifications, septal wall thickening (M-mode echocardiography), left ventricular pressures and time derivatives were measured at baseline and at 30, 60 and 90 s after balloon inflation and 120 s after balloon deflation. RESULTS: Intracoronary electrocardiographic analysis showed that the time course of the maximal ST segment elevation was identical at each inflation, as were wall motion changes assessed by the decrease in septal wall thickening. For the first and last inflations, peak positive dP/dt decreased significantly by 13 +/- 9% (mean +/- SD) and 14 +/- 13%, whereas peak negative dP/dt increased by 23 +/- 15% and 22 +/- 10%, respectively (all p < 0.01 from baseline values). The relaxation time constant, tau, was altered similarly during the different inflations, from 44 +/- 6 to 74 +/- 13 ms and from 57 +/- 13 to 77 +/- 13 ms (all p < 0.001) for the first and last inflations, respectively. Left ventricular end-diastolic pressure increased to the same level after each inflation. In contrast to other hemodynamic variables, tau and left ventricular end-diastolic pressure did not return to baseline values in between the inflations, which may be due to myocardial stunning. CONCLUSIONS: In patients with proximal left anterior descending coronary artery stenosis and no evidence of collateral circulation, brief periods of ischemia, such as those used during routine coronary balloon angioplasty, do not provide any protection against myocardial ischemia.
BACKGROUND: After angioplasty coronary reserve improves but does not normalize in most patients. The purpose of this study was to examine before and after angioplasty coronary reserve and transmural myocardial blood flow distribution using myocardial contrast echocardiography. METHODS AND RESULTS: Twelve patients with left anterior descending coronary artery stenosis were investigated before and immediately after angioplasty. A Doppler catheter was placed in the proximal segment. Myocardial contrast echocardiography was performed by imaging the septum in M mode in a parasternal view using a 3.0-mL bolus of sonicated amidotrizoate sodium meglumine through the guiding catheter. The gray level before injection was subtracted from the gray level after injection to maximize contrast time-intensity curves. The area under the curve was used as an indicator of myocardial blood flow, and subendocardial/subepicardial ratios were measured. After baseline measurements were obtained, Doppler and echographic data were recorded after a bolus infusion of papaverine into the left main coronary artery. The same protocol was performed in patients after angioplasty and in five control subjects with normal coronary arteries. Before angioplasty, echocardiographic and Doppler coronary reserve were 2.57 +/- 0.48 and 2.54 +/- 0.57, respectively. Both increased after angioplasty to 3.65 +/- 0.57 and 3.36 +/- 0.70, respectively (P < .05). Coronary reserve values obtained in patients with these two methods under the different conditions and in control subjects were correlated (r = .81; P = .0001). Before angioplasty, subendocardial/subepicardial septal ratios decreased from 0.80 +/- 0.48 to 0.60 +/- 0.27 after papaverine (P < .05). However, after angioplasty, these ratios tended to increase, from 0.72 +/- 0.27 to 0.92 +/- 0.45 after papaverine, but they did not change in control subjects (1.11 +/- 0.23 to 0.92 +/- 0.11). CONCLUSIONS: These results show that myocardial contrast echocardiography yields flow reserve values that correlate with values obtained using intracoronary Doppler. This technique may be considered as an accurate tool to assess coronary reserve in humans.
Increased vascular production of nitric oxide (NO) may contribute to the peripheral vasodilation and hyperdynamic state complicating advanced liver cirrhosis. In this study, we examined the effect on forearm blood flow of local brachial artery infusion of noradrenaline (NA) and NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO-synthase, in 10 alcoholic ascitic cirrhotic patients (patients with decompensated alcohol-induced liver disease: DALD group) and 10 patients with well-compensated alcohol-induced liver disease (CALD group). Forearm blood flow was measured by venous occlusion plethysmography. As compared with the CALD group, the DALD group had higher cardiac index and forearm blood flow as well as lower systemic blood pressure and vascular resistance. Infusions of NA and L-NMMA produced similar reduction in resting blood flow in the CALD group. However, in the DALD group, NA was significantly less effective than L-NMMA. The forearm vasoconstrictor response to NA was also significantly reduced in the DALD group when compared with the CALD group. In the DALD group, NA decreased forearm blood flow by 21.0 +/- 6.2% and increased vascular resistance by 37.2 +/- 12.3%, whereas respective changes in the CALD group were 41.8 +/- 6.2% (P < .01) and 77.8 +/- 9.9% (P < .02). In contrast, L-NMMA induced greater forearm vasoconstriction in the DALD group than in the CALD group. In decompensated patients, L-NMMA decreased forearm blood flow by 50.4 +/- 2.7% and increased vascular resistance by 115.9 +/- 14.4%, whereas changes in compensated patients were 38.2 +/- 4.9% (P < .05) and 77.4 +/- 16.2% (NS), respectively. These results are consistent with the hypothesis that increased vascular synthesis of NO contributes to the high dynamic state of patients with advanced cirrhosis.
Coronary vasomotion dependent on the endothelium and on the smooth muscle has been intensively studied by quantitative angiography and intracoronary Doppler. Intracoronary ultrasound is a new imaging technique which allows precise measurement of the section of the coronary artery. This study was undertaken to assess the value of intracoronary ultrasound in the investigation of epicardial coronary artery vasomotion. Twenty hypercholesterolaemic patients with irregularity of the arterial lumen on angiography and 6 normo-cholesterolaemic subjects with normal coronary angiogram (control group) were included. An intracoronary ultrasonic catheter with a rotating mirror (4.3 French, CVIS) emitting at 30 MHz was positioned in the proximal segment of a coronary artery. Endothelial function was studied during sympathetic stimulation by a cold pressor test and during increased coronary flow by local injection of papaverine. The intima of the coronary arteries of the patient group was significantly thicker than that of the control group. The cold test induced significant paradoxical vasoconstriction of the atheromatous coronary arteries and a significant vasodilatation of the coronary arteries of the control group. The increased coronary flow tended to constrict the ateromatous arteries but significantly dilated the normal arteries. Administration of Linsidomine (SIN-1) induced vasodilatation by direct relaxation of the smooth muscle in both groups. No correlation was observed between the thickness of the intima measured by intracoronary ultrasound and the abnormal vasomotor response to the vasomotion different stimuli. The results of this study concord with those of studies of coronary by quantitative angiography. Intracoronary ultrasound provides an accurate method of studying coronary endothelial function and the vasomotor tone of the epicardial coronary arteries.
A microcomputer-based system has been developed for automatically analysing M-mode echocardiograms. This system can be used on images directly transferred from an echograph to the microcomputer. To obviate the major disadvantage of echocardiography, its poor signal-to-noise (S/N) level, the system conducts, first, an image restoration based on the quasi-periodicity of cardiac cycles, then border extraction is performed, using methods based on template matching using dynamic cardiac information present in the echocardiograms.
This study was performed to evaluate the accuracy of intravascular ultrasound for the assessment of coronary artery vasomotion and endothelial function in patients with atherosclerosis. Twenty patients with luminal irregularities on the coronary angiogram and a high cholesterol level (287 +/- 19 mg/dl) (group 1) and six patients with angiographically smooth arteries and a minimally elevated cholesterol level (197 +/- 12 mg/dl) (group 2) were studied. A mechanical intravascular ultrasound probe (4.3F) was placed into the proximal segment of the coronary artery. The ultrasound images were recorded on super VHS videotape and were then digitized allowing the measurement of the lumen area and then the calculation of a mean intimal thickness index. Endothelial function was studied during sympathetic stimulation by a cold pressor test and, after increasing coronary blood flow, by intracoronary papaverine administration; a 1 mg bolus of linsidomine was then administered into the coronary artery. Patients in group 1 had a higher mean intimal thickness (1.52 +/- 0.64 mm) than those in group 2 (0.18 +/- 0.08 mm) (p < 0.001). In response to sympathetic stimulation, a vasoconstricting effect occurred in group 1 (9.5 +/- 1.3 mm2 vs 11.4 +/- 1.2 mm2 at baseline, p < 0.05), while a vasodilating action was observed in the control group (11.6 +/- 2.1 mm2 vs 10.4 +/- 1.8 mm2 at baseline, p < 0.05). After papaverine infusion, a trend toward a vasoconstricting effect was observed in response to increased flow in group 1 (10 +/- 1.3 mm2 vs 11.4 +/- 1.2 mm2 at baseline, p < 0.05). that was not observed in group 2 (9.4 +/- 2 mm2 vs 8.9 +/- 1.9 mm2, p = NS). Linsidomine infusion induced a significant vasodilating effect in both groups (p < 0.001). In conclusion, intravascular ultrasound may be considered a useful tool to assess endothelial function of large coronary arteries and to obtain the precise relationship between wall thickness and the vasomotor response.
OBJECTIVES: This study was designed to evaluate the relation between the velocity of flow propagation and left ventricular relaxation by using color M-mode Doppler echocardiography to analyze flow propagation in the left ventricle. BACKGROUND: Noninvasive attempts to identify alterations in left ventricular relaxation have been hampered because both the relaxation rate and left atrial filling pressure are the determinants of peak early velocity and filling rate. METHODS: Color M-mode velocity data were transferred to a microcomputer and compared with conventional pulsed Doppler data to assess the ability of color M-mode echocardiography to analyze velocity field properties. The velocity of flow propagation was measured as the slope of the flow wave front during early filling in normal subjects (n = 29) and in patients with disease that alters relaxation (dilated cardiomyopathy [n = 31], ischemic cardiomyopathy [n = 8], hypertrophic cardiomyopathy [n = 5], systemic hypertension [n = 22] and aortic valve disease [n = 25]). In nine patients with end-stage dilated cardiomyopathy, echocardiographic and left heart catheterization data were obtained at baseline and during intracoronary dobutamine infusion. RESULTS: Color M-mode and pulsed Doppler echocardiographic data were highly correlated (n = 217, r = 0.94, p less than 0.0001, velocity range 0.2 to 1.5 m/s). The velocity of flow propagation was lower in patients than in normal subjects (0.46 +/- 0.15 vs. 0.84 +/- 0.11 m/s, p less than 0.0001). The decrease was significant in all disease forms with or without left ventricular dilation. The velocity of flow propagation was related to peak early velocity in normal subjects (p less than 0.001) but not in patients. It varied inversely with the isovolumetric relaxation time constant during dobutamine infusion and the two variables were highly correlated (p less than 0.0001). CONCLUSIONS: The velocity of flow propagation during early filling seems to be highly dependent on the left ventricular relaxation rate and could be an important tool in studying diastolic function.
We compared the cumulative dose-response curves obtained during carbachol inhalation by simultaneous measurements of airway specific conductance (sGaw) and respiratory conductance, in 23 subjects with or without bronchial hyperresponsiveness. The sGaw was measured by a body plethysmograph, whilst the random noise forced oscillation technique (FOT) was used to determine respiratory conductance. The sGaw was compared to respiratory conductance extrapolated to zero frequency (Grs0). Bronchial sensitivity was assessed by the threshold dose of carbachol (TD) that induced a decrease in sGaw and Grs0 of twice the baseline coefficient of variation. Bronchial responsiveness was assessed by the slopes (S) of the individual dose-response curves. The TD and S values obtained by FOT and by plethysmography were closely correlated (p less than 0.001). The carbachol doses inducing a 50% reduction in sGaw were equivalent to those causing a 42% reduction in Grs0 (r = 0.90; p less than 0.001). During bronchial challenge testing, FOT provides comparable information in terms of bronchial sensitivity and responsiveness to that supplied by plethysmography.