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Biomedical subjects

A Barsotti

Publications and source records attributed to A Barsotti.

At least 37 records · Page 2Linked to original sources

Oxygen-free radical decrease in hypertensive patients treated with lercanidipine.

BACKGROUND: The relationship between oxidative stress, lipoproteins, cardiovascular risk factors and vascular disease progression has recently attracted fresh attention due to the possibility of measuring free radicals (FRs). The aim of this study was to evaluate blood plasma variations in oxygen FRs in hypertensive patients treated with lercanidipine, a drug acting on blood pressure and microcirculation. METHODS: Twenty-two patients with moderate hypertension (M:F=12:10; age=52) and no vascular disease (evaluated by high-resolution ultrasound) were treated for 24 weeks with Lercanidipine (10 mg/day or 20 mg/day if BP values did not decrease at least 15 percent after four weeks of treatment). BP was measured at inclusion and after 4, 8, 12 and 24 weeks of treatment. FRs measurements (using the D-Roms test) were made at inclusion, at the 8th, 12th and 24th week. RESULTS: All patients completed the treatment which was well tolerated and without side effects. Systolic and diastolic BP decreased after 8, 12 (p<0.05) and 24 weeks (at 24 weeks systolic pressure was decreased by 21.1 percent, and diastolic by 11.1 percent; p<0.02). FRs levels progressively decreased from 541 Carr Units (SD 54) at inclusion to 411 (SD 56) at eight weeks (p<0.05), to 401 (SD 35) (p<0.05) at 12 weeks and finally to 398 (SD 33), (p<0.02) at 24 weeks of treatment (72.2 percent of the initial value). CONCLUSIONS: The possibility of measuring FRs in vivo with a simple, inexpensive test allows the identification of subjects with a high level of oxidative stress, and the monitoring of the effects of treatments. Lercanidipine, acting on blood pressure, on the microcirculation and decreasing oxidative stress and Frs plasma levels may effectively decrease the rate of progression of cardiovascular diseases offering the advantage of an increased level of protection in patients with high levels of oxidative stress.

Adult↗

Endothelial NOS expression and ischemia-reperfusion in isolated working rat heart from hypoxic and hyperoxic conditions.

Induction of endothelial nitric oxide synthase (eNOS) contributes to the mechanism of heart protection against ischemia-reperfusion damage. We analyzed the effects of hypoxia and hyperoxia on eNOS expression in isolated working rat hearts after ischemia-reperfusion damage. Adult male Wistar rats were submitted to chronic hypoxia (2 weeks) and hyperoxia (72 h). The hearts were submitted to 15 min of ischemia and reperfused for 60 min, then we evaluated hemodynamic parameters and creatine phosphokinase (CPK) release. eNOS expression was estimated by RT-PCR; enzyme localization was evaluated by immunohistochemistry and the eNOS protein levels were detected by Western blot. All hemodynamic parameters in hypoxic conditions were better with respect to other groups. The CPK release was lower in hypoxic (P<0.01) than in normoxic and hyperoxic conditions. The eNOS deposition was significantly higher in the hypoxic group versus the normoxic or hyperoxic groups. The eNOS protein and mRNA levels were increased by hypoxia versus both other groups. Chronic hypoxic exposure may decrease injury and increase eNOS protein and mRNA levels in heart subjected to ischemia-reperfusion.

Animals↗

Nomograms used to define the short-term treatment with PGE(1) in patients with intermittent claudication and critical ischemia. The ORACL.E (Occlusion Revascularization in the Atherosclerotic Critical Limb) Study Group. The European Study.

Infusional, cyclic PGE1 treatment is effective in patients with intermittent claudication and critical limb ischemia (CLI). One of the problems related to chronic PGE1 treatment in vascular diseases due to atherosclerosis is to evaluate the variations of clinical conditions due to treatment in order to establish the number of cycles per year or per period (in severe vascular disease reevaluation of patients should be more frequent) needed to achieve clinical improvement. In a preliminary pilot study a group of 150 patients (mean age 67+/-12 years) with intermittent claudication (walking range from 0 to 500 m) and a group of 100 patients with CLI (45% with rest pain, and 55% gangrene; mean age 68 +/-11 years) the number of PGE1 cycles according to the short-term protocol (STP) needed to produce significant clinical improvement was preliminarily evaluated. Considering these preliminary observations, the investigators established a research plan useful to produce nomograms indicating the number of cycles of PGE1-STP per year needed to improve the clinical condition (both in intermittent claudication and CLI). A significant clinical improvement was arbitrarily defined as the increase of at least 35% in walking distance (on treadmill) and/or the disappearance of signs and symptoms of critical ischemia in 6 months of treatment in at least 75% of the treated patients. With consideration of the results obtained with the preliminary nomograms a larger validation of the nomograms is now advisable. A cost-effectiveness analysis is also useful to define the efficacy of treatment on the basis of its costs. The publication of this report in two angiological journals (Angeiologie and Angiology) will open the research on nomograms to all centers willing to collaborate to the study. The data are being collected in the ORACL.E database and will be analyzed within 12 months after the publication of this report.

Aged↗

PGE(1) treatment of severe intermittent claudication (short-term versus long-term, associated with exercise)--efficacy and costs in a 20-week, randomized trial.

The efficacy, safety, and cost of prostaglandin E1 (PGE1) in the treatment of severe intermittent claudication was studied comparing a long-term treatment protocol (LTP) with a short-term treatment protocol (STP) in a randomized 20-week study. The study included 980 patients (883 completed the study) with an average total walking distance of 85.5 +/-10 m (range 22-119). Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP, phase 2 was the main treatment phase. In the LTP, treatment was performed with 2-hour infusions (60 microg PGE1, 5 days each week for 4 weeks. In phase 3 (4-week interval period) PGE1 was administered twice a week (same dosage). In phase 4 (monitoring lasting 3 months, from week 9 to 20) no drugs were used. In STP phase 2 treatment was performed in 2 days by a 2-hour infusion (first day: morning 20 microg, afternoon 40 microg; second day morning and afternoon 60 microg). The reduced dosage was used only at the first cycle (week 0) to evaluate tolerability or side effects. Full dosage (60 microg bid) was used for all other cycles. The same cycle was repeated at the beginning of weeks 4, 8, and 12. The observation period was between weeks 12 and 20. A treadmill test was performed at inclusion, at the beginning of each phase, and at the end of 20th week. A similar progressive physical training plan (based on walking) and a reduction in risk factors levels plan was used in both groups. Intention-to-treat analysis indicated an increase in walking distance, which improved at 4 weeks and at 20 weeks in the STP more than in the LTP group. At 4 weeks the variation (increase) in pain-free walking (PFWD) was 167.8% (of the initial value) in the LTP group and 185% in the STP group (p<0.05). At 4 weeks the variation (increase) in total walking distance (TWD) was 227.6% of the initial value in the LTP group and 289% in the STP group (p<0.05). At 20 weeks the increase in PFWD was 496% of the initial value in the LTP group vs 643% in the STP group (147% difference; p<0.02). The increase in TWD was 368% in the LTP group and 529% in the STP group (161% difference; p<0.02). In both groups there was a significant increase in PFWD and TWD at 4 and 20 weeks, but results obtained with STP are better considering both walking distances. No serious drug-related side effects were observed. Local, mild adverse reactions were seen in 6.3% of the treated subjects in the LTP and 3% in the STP. Average cost of LTP was 6,664 Euro; for STP the average costs was approximately 1,820 E. The cost to achieve an improvement in walking distance of 1 m was 45.8 E with the LTP and 8.5 E with the STP (18% of the LTP cost; p<0.02). For an average 100% increase in walking distance the LTP cost was 1,989 E vs. 421 E with STP (p<0.02). Between-group analysis favors STP considering walking distance and costs. Results indicate good efficacy and tolerability of PGE, treatment. With STP less time is spent in infusion and more in the exercise program. STP reduces costs, speeds rehabilitation, and may be easily used in a larger number of nonspecialized units.

Aged↗

Coronary aneurysms and stenosis detected with magnetic resonance coronary angiography in a patient with Kawasaki disease.

Coronary artery abnormalities in Kawasaki syndrome develop in about 15-25% of young patients, mostly as aneurysms. In the long-term evolution of coronary artery disease thrombotic occlusion of aneurysms, premature atherosclerosis, and stenosis, are observed. Magnetic resonance is an emerging modality in the angiographic assessment of coronary arteries. The authors report a case of coronary artery aneurysms and stenosis in a 26-year-old patient with Kawasaki disease detected by magnetic resonance coronary angiography and confirmed by conventional coronary angiography.

Adult↗

[Is a totally non-invasive assessment of the hemodynamic profile possible in patients with chronic heart failure?].

Relevant hemodynamic information can be obtained by a comprehensive Doppler echocardiographic examination in patients with various cardiac diseases. The assessment of left heart hemodynamics by Doppler echocardiography has been addressed by several investigators. The feasibility and the accuracy of methods for the estimation of left ventricular filling pressure and cardiac output have been validated by comparative right heart catheterization. Studies have shown that Doppler echocardiography can allow the measurement of pulmonary artery pressures from the pressure gradients across the tricuspid and pulmonary valves. The possibility of completely characterizing cardiac hemodynamics noninvasively has recently been documented: in patients with acute myocardial infarction, automated cardiac output measurement along with the assessment of left ventricular filling by Doppler echocardiography may be used for the identification of hemodynamic subsets. Although Doppler echocardiography can provide noninvasive measures of hemodynamic indices, its value has been disputed since the technique is patient-dependent, time-consuming and requires meticulous acquisition and interpretation by skilled operators. The use of contrast agents may improve the accessibility of both right-sided and left-sided Doppler signals, potentially increasing the number of patients to whom the noninvasive hemodynamic assessment could be applied.

Chronic Disease↗

Usefulness of a tilt training program for the prevention of refractory neurocardiogenic syncope in adolescents: A controlled study.

BACKGROUND: Recurrent syncope represents a debilitating disorder and quality of life deteriorates as a function of recurrence of symptoms. Although the administration of beta-blockers, vasoconstrictors, fludrocortisone, and serotonin reuptake inhibitors may be helpful in preventing episodes, many patients are intolerant of or respond poorly to these agents. Orthostatic training has been reported to be effective in preventing refractory syncope. Thus, to determine whether a tilt training program could prevent symptoms in adolescents, the following controlled study was undertaken. METHODS AND RESULTS: Forty-seven consecutive adolescents (18 male and 29 female, mean age 16.0+/-2.2 years) with recurrent syncope and positive head-up tilt test refractory to previous traditional therapies were distributed between 2 groups, depending on their consent (24 patients) or refusal (controls, 23 patients) to enter the program. Orthostatic training was started, in the presence of a family member, with a series of 5 in-hospital sessions. The 24 patients and their relatives were then instructed to perform the tilt training at home by standing against a wall twice a day for a planned duration of up to 40 minutes, depending on the in-hospital orthostatic tolerance. Head-up tilt response was reevaluated after 1 month, and the clinical effect was noted over a mean follow-up of 18. 2+/-5.3 months (range 15 to 23); 26.1% of patients in the control group and 95.8% of patients in the training group became tilt-negative (P<0.0001). Spontaneous syncope was observed in 56.5% versus 0% in the control and training group, respectively (P<0.0001). CONCLUSIONS: Orthostatic training was found to significantly improve symptoms of adolescents with neurocardiogenic syncope unresponsive to or intolerant of traditional medications. Twice-a-day training sessions of 40 minutes were well accepted by patients.

Adolescent↗

Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: The purpose of the study was to determine whether the well tolerated serotonin reuptake inhibitor paroxetine hydrochloride could prevent vasovagal syncope in patients resistant to or intolerant of previous traditional therapies. BACKGROUND: Serotonergic mechanisms play a major role in the processes leading to neurocardiogenic vasovagal syncope, and serotonin reuptake inhibitors have been reported to be effective in preventing refractory syncope. METHODS: Sixty-eight consecutive patients (26 men and 42 women, mean age 44.7+/-16.5 years) with recurrent syncope and positive head-up tilt test and in whom standard therapies with beta-adrenergic blocking agents, vagolytic, negative inotropic or mineral corticoid agents were ineffectual or poorly tolerated were referred for study. Patients randomly received either paroxetine at 20 mg once a day or a placebo. A head-up tilt test was then reperformed after one month of treatment, and the clinical effect was noted over a mean follow-up of 25.4+/-7.9 months. RESULTS: The response rates (negative tilt test) after one month of treatment were 61.8% versus 38.2% (p < 0.001) in the paroxetine and placebo groups, respectively. During follow-up spontaneous syncope was reported in six patients (17.6%) in the paroxetine group as compared to 18 patients (52.9%) in the placebo group (p < 0.0001). Only one patient (2.9%) asked to be discontinued from the drug for severe side effects. CONCLUSIONS: Paroxetine was found to significantly improve the symptoms of patients with vasovagal syncope unresponsive to or intolerant of traditional medications and was well tolerated by patients.

Acute Disease↗

Surgical treatment of dilated cardiomyopathy with conventional techniques.

OBJECTIVE: We review our surgical experience using different conventional surgical techniques in the surgical treatment of the dilated cardiomyopathy (DCMP) in non-transplant eligible patients. METHODS: In this series we included patients who fit the following criteria: ejection fraction < 35%; end diastolic volume > or = 110 ml/m2; enlargement of the base of the heart (maximal mitral diameter > or = 22 mm/m2) with functional mitral regurgitation; mitral surgery to be performed in every case. Moreover, two groups were considered. (A) Normal or moderately impaired right ventricular function; PAP < 45 mmHg; elective or semielective surgery. (B) Severely impaired right ventricular function; PAP > or = 45 mmHg; severe organ failure; dependency on IABP and/or inotropes; need of ICU stay. From January 1990 to September 1998, 66 patients underwent isolated mitral valve surgery (n = 30); in the remaining 36 the Batista operation (n = 21) or exclusion of akinetic areas (n = 15) were associated. The etiology was ischemic in 42, idiopathic in 23 and post-valvular in one. RESULTS: When isolated mitral valve surgery was performed, early mortality in group A (n = 22) was 0, in group B (n = 8) 50%. Overall 5-year survival was 70.0 +/- 8.4. in group A 81.8 +/- 8.2, and in group B 37.5 +/- 17.1. When the Batista operation was performed, early mortality in group A (n = 13) was 23.1%, in group B (n = 8) 75%. Overall 2-year survival was 42.9 +/- 10.8 in group A 61.5 +/- 13.5 and in group B 25.0 +/- 15.3. When akinetic areas were excluded, early mortality in group A (n = 11) was 18.2% and in group B (n = 4) 100%. Overall 1-year survival was 53.3 +/- 12.9, in group A 72.7 +/- 13.4. CONCLUSION: Group A patients have better results in every cohort of patients considered. Even if patients selection seems to be the most important variable for early mortality and late survival, isolated mitral valve surgery, when feasible, provides the best early and late results.

Adult↗

Shock waves (SW) noninvasive extracorporeal thrombolysis treatment (NISWT).

A group of 24 patients were considered for noninvasive shock waves thrombolysis (NISWT). Of these, 15 patients gave their informed consent. NISWT was attempted in eight patients (while seven patients were randomized for follow-up only). NISWT was possible in six of seven patients. In one patient randomized for NISWT, local inguinal scarring, due to previous surgery, made impossible the visualization of the femoral vein, and therefore focusing of shock waves (SWs). No side effects were reported in the days after SWs administration during the 4-month follow-up. In patients treated with NISWT it was possible to observe just after the SWs session the presence of echolucent "acoustic holes" and flow (by color and power Doppler) within the "holes." All "echolucent holes" produced at the first session were still present at 4 months, and color flow imaging also detected new flow channels in echogenic areas of thrombi previously not visible. In one patient thrombolysis was achieved after the first treatment, but at 3 and 4 months the thrombus was completely avascular. In conclusion, thrombolysis using SWs was obtained in selected cases and it was still persisting at 4 months in six of the seven treated patients. NISWT appears feasible and promising. These results should be confirmed by larger, prospective trials.

Adult↗

Comparison of low-molecular-weight heparin, administered primarily at home, with unfractionated heparin, administered in hospital, and subcutaneous heparin, administered at home for deep-vein thrombosis.

In this study, 294 patients with acute proximal DVT (deep venous thrombosis) were randomly assigned to receive intravenous standard heparin in the hospital (98 patients) or low-molecular-weight heparin (LMWH) (nadroparin 0.1 mL [equivalent to 100 AXa IU] per kg of body weight subcutaneously twice daily) administered primarily at home (outpatients) or alternatively in hospital (97 patients) or subcutaneous calcium heparin (SCHep) (99 patients, 0.5 mL bid) administered directly at home. The study design allowed outpatients taking LMWH heparin to go home immediately and hospitalized patients taking LMWH to be discharged early. Patients treated with standard heparin or LMWH received the oral anticoagulant starting on the second day, and heparin was discontinued when the therapeutic range (INR 2-3) had been reached. Anticoagulant treatment was maintained for 3 months. Patients treated with SCHep were injected twice daily for 3 months without oral anticoagulants. Patients were evaluated for inclusion and follow-up with color duplex scanning. Venography was not used. In case of suspected pulmonary embolism (PE) a ventilatory-perfusional lung scan was performed. Endpoints of the study were recurrent or extension of DVT, bleeding, the number of days spent in hospital, and costs of treatments. Of the 325 patients included, 294 completed the study. Dropouts totaled 31 (10.5%); six of the 325 included patients (1.8%) died from the related, neoplastic illness. Recurrence or extension of DVT was observed in 6.1% of patients in the LMWH group, in 6.2% in the standard heparin group, and in 7.1% in the SCHep group. Most recurrences (11/17) were in the first month in all groups. Bleedings were all minor, mostly during hospital stay. Hospital stay in patients treated with LMWH was 1.2+/-1.4 days in comparison with 5.4+/-1.2 in those treated with standard heparin. There was no hospital stay in the SCHep group. Average treatment costs in 3 months in the standard heparin group (US $2,760) were considered to be 100%; in comparison costs in the LMWH group was 28% of the standard heparin and 8% in the SCHep group. This study indicated that LMWH and SCHep can be used safely and effectively to treat patients with proximal DVT at home at a lower cost.

Ambulatory Care↗

[Simvastatin and ischemia-reperfusion damage: its effects on apoptotic myocyte death and on the endothelial expression of nitric-oxide synthetase in an experimental model of the isolated rat heart].

Recent studies have suggested that simvastatin may exert endothelial-protective and anti-ischemic effects via nitric oxide (NO) mechanisms. The aim of this study was to evaluate, in isolated working rat hearts, the effect of acute simvastatin administration on endothelial and inducible NO-synthase (eNOS and iNOS) mRNA and on myocytic apoptosis after ischemia-reperfusion. We used isolated working rat hearts submitted to 15 min global, no-flow, normothermic ischemia and 180 min reperfusion. To detect myocytic apoptosis we used DNA agarose gel electrophoresis and Tunel technique; eNOS and iNOS expression were evaluated by multiplex reverse transcriptase-polymerase chain reaction; glyceraldehyde-3-phosphate dehydrogenase (G3PDH) was used as standard. The eNOS and iNOS mRNAs were expressed as G3PDH/eNOS and G3PDH/iNOS densitometric ratio (BioRad Gel Doc 1000). Hearts were divided into four groups: A) hearts excised and used as histological controls; B) untreated hearts submitted to ischemia and reperfusion; C) actinomicin D-treated (1.5 mg/kg) hearts, perfused with 25 microM simvastatin, subjected to ischemia and reperfusion; D) hearts treated with simvastatin 25 microM and submitted to ischemia and reperfusion. In Group B we evidenced a significant myocytic apoptotic damage, reduced in groups C and D. In Group B an increase in G3PDH/eNOS ratio vs Group A was detected; in Group D a reduction in G3PDH/eNOS ratio vs Group B occurred; no significant changes were observed between groups C and D. As for G3PDH/iNOS ratio, it was significantly increased in Group D with respect to groups A and B. Our data suggest that simvastatin in acute may modulate NO-synthase mRNA expression (induction of eNOS mRNA by means of post-transcriptional mechanisms and inhibition of iNOS postischemic overexpression) and reduce myocytic apoptosis.

Acute Disease↗