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Biomedical subjects

G Parrinello

Publications and source records attributed to G Parrinello.

At least 37 records · Page 2Linked to original sources

Comparison of the effects of felodipine and cilazapril on exercise performance in patients with mild to moderate hypertension. A crossover study.

This double-blind crossover study was designed to compare the effects of felodipine and cilazapril on exercise performance in hypertensive patients. After a 2-week placebo run-in period, 40 patients with mild to moderate hypertension were randomized into two parallel groups to receive either felodipine (10 mg) or cilazapril (5 mg) for 4 weeks. After another 2-week washout period, treatments were then crossed over for a further 4-week study period. All patients were given an extensive rest and exercise evaluation at the end of the placebo period. Extensive rest and exercise evaluations were repeated after a 4-week treatment period and again after the second washout period and after the second 4-week treatment period. Before each exercise test, epinephrine, norepinephrine and dopamine plasma levels and plasma renin activity were measured. Two groups were similar at baseline for systolic and diastolic blood pressure and heart rate as well as for laboratory and hormonal variables and duration of exercise test. At the end of treatment diastolic blood pressure was significantly reduced in the felodipine group (p = 0.019). Duration of exercise test was longer than at baseline (p = 0.031) in the felodipine group. Plasma dopamine levels were significantly increased in the cilazapril group. Plasma renin activity significantly increased in the felodipine group. In conclusion, our data show that the two drugs have the same effectiveness in resting conditions but that felodipine is more effective in lowering maximum exercise diastolic blood pressure and in improving exercise time with an double product increase (not significant); it has no statistically significant effect on maximal exercise systolic blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗

Serum from patients with severe heart failure downregulates eNOS and is proapoptotic: role of tumor necrosis factor-alpha.

BACKGROUND: Cytokine activation and endothelial dysfunction are typical phenomena of congestive heart failure (CHF). We tested the hypothesis that incubating human umbilical vein endothelial cells with serum from patients with CHF will downregulate endothelial constitutive nitric oxide synthase (eNOS) and induce apoptosis. METHODS AND RESULTS: We studied 21 patients with severe CHF. Levels of tumor necrosis factor-alpha (TNF-alpha) and several neuroendocrine parameters were assessed. eNOS was measured by Western Blot analysis and apoptosis by optical microscopy and flow cytometry. We observed (1) eNOS downregulation (difference versus healthy subjects at 24 hours [P<0.05] and 48 hours [P<0.001]), (2) nuclear morphological changes typical of apoptosis; and (3) a high apoptotic rate with propidium iodide (increasing from 2.1+/-0.4% to 11.3+/-1.2% at 48 hours; P<0.001 versus healthy subjects) and annexin V. An anti-human TNF-alpha antibody did not completely counteract these effects. A strong correlation existed between eNOS downregulation and apoptosis (r = -0.89; P<0.001). CONCLUSIONS: Serum from patients with severe CHF downregulates eNOS expression and increases apoptosis. High levels of TNF-alpha likely play a role, but they cannot be the only factor responsible.

Aged↗

Carotid atherosclerosis in renal transplant recipients: relationships with cardiovascular risk factors and plasma lipoproteins.

BACKGROUND: Renal transplant recipients have an increased incidence of cardiovascular disease, but less data exist about cerebrovascular atherosclerosis. In this study, we assessed the prevalence of carotid lesions as evaluated by B-mode ultrasonography in a group of renal transplant recipients, and we evaluated univariate and multivariate relationships between common risk factors and plasma lipoproteins and carotid lesions. METHODS: Fifty-seven renal transplant recipients and 113 age- and gender-matched controls underwent a complete clinical visit for the evaluation of risk factors present. In all subjects, a blood sample was collected for lipoprotein determination, and an ultrasound high-resolution B-mode imaging examination of the common carotid arteries was performed. RESULTS: We found that among renal transplant recipients, there was a significantly increased prevalence of subjects with plaque in comparison with controls (24.6% vs. 6.2%, P<0.001). At multiple analysis, carotid lesions were independently associated with age, hypertension, diabetes, smoking habit, and the presence of cardiovascular disease in controls and with age and hypertension in renal transplant recipients. Neither the lipid profile nor the presence of dyslipidemias was related to carotid score in renal transplant recipients, whereas a nonsignificant trend was observed in controls. Finally, in transplant patients, we did not find any association between carotid lesions and high-density lipoprotein subfractions. CONCLUSIONS: Age and hypertension are the main predictors of extracranial cerebrovascular atherosclerosis after renal transplantation. Because carotid lesions may represent a useful predictive marker of clinical events in nontransplant subjects, carotid artery evaluation by B-mode ultrasound might be routinely included in the management of renal transplant patients.

Adult↗

Postlaryngectomy pharyngocutaneous fistula: incidence, predisposing factors, and therapy.

BACKGROUND: Pharyngocutaneous fistula is the most common complication following total laryngectomy. The present study was designed to determine the incidence and predisposing factors and to describe the management of the complication. METHODS: The records of 246 consecutive patients who underwent total laryngectomy for squamous cell carcinoma were reviewed. We evaluated 23 factors potentially predisposing to fistula formation (age, sex, smoking and drinking habits, hypertension, diabetes, chronic bronchitis, chronic congestive heart failure, anesthesiologic risk, cholinesterase level, pre- and postoperative hemoglobin and albumin levels, previous treatment, previous tracheotomy, site of origin of the tumor, surgical procedure, concurrent neck dissection, suture material, status of surgical margins, clinical stage, and histologic grade) using the chi-squared test and logistic regression analysis. RESULTS: A pharyngocutaneous fistula developed in 16% of patients within a mean time of 11 days from surgery. Spontaneous closure with local wound care was achieved in 70% of cases. Ten patients required surgical closure by direct suture of the pharyngeal mucosa; a deltopectoral flap and a pectoralis major myocutaneous flap were used in one case each. The mean healing time was 39+/-46 days in the group of patients requiring surgical closure, compared with 19+/-12 days in the group in which spontaneous closure occurred. The definitive model of logistic regression analysis showed that pharyngolaryngectomy, chronic congestive heart failure, and postoperative hemoglobin level lower than 12.5 g/dL carried respectively a two-, five-, and ninefold increase in the risk of fistula development. The model, with a specificity of 81%, is fairly good in identifying patients with a low risk of fistula. CONCLUSIONS: The results observed in the group of patients under analysis corroborated the relevance of factors such as the extension of laryngectomy and postoperative hemoglobin level on fistula occurrence. However, chronic congestive heart failure, which is an expression of disturbance of the organism, emerged for the first time as an additional statistically significant risk factor for pharyngocutaneous fistula formation. Our experience confirmed that most fistulas can be successfully managed with conservative treatment. Except for the rare cases in which large defects are present, direct suture is appropriate when conservative treatment has failed.

Adult↗

Surface mechanomyogram reflects the changes in the mechanical properties of muscle at fatigue.

The contractile properties of muscle are usually investigated by analysing the force signal recorded during electrically elicited contractions. The electrically stimulated muscle shows surface oscillations that can be detected by an accelerometer; the acceleration signal is termed the surface mechanomyogram (MMG). In the study described here we compared, in the human tibialis anterior muscle, changes in the MMG and force signal characteristics before, and immediately after fatigue, as well as during 6 min of recovery, when changes in the contractile properties of muscle occur. Fatigue was induced by sustained electrical stimulation. The final aim was to evaluate the reliability of the MMG as a tool to follow the changes in the mechanical properties of muscle caused by fatigue. Because of fatigue, the parameters of the force peak, the peak rate of force production and the peak of the acceleration of force production (d2F/dt2) decreased, while the contraction time and the half-relaxation time (1/2-RT) increased. The MMG peak-to-peak (p-p) also decreased. The attenuation rate of the force oscillation amplitude and MMG p-p at increasing stimulation frequency was greater after fatigue. With the exception of 1/2-RT, all of the force and MMG parameters were restored within 2 min of recovery. A high correlation was found between MMG and d2F/dt2 in un-fatigued muscle and during recovery. In conclusion, the MMG reflects specific aspects of muscle mechanics and can be used to follow the changes in the contractile properties of muscle caused by localised muscle fatigue.

Adult↗

Changes in oxidative stress and cellular redox potential during myocardial storage for transplantation: experimental studies.

BACKGROUND: Cardioplegic solutions assure only a sub-optimal myocardial protection during prolonged storage for transplantation. The ultimate cause of myocardial damage during storage is unknown, but oxygen free radicals might be involved. We evaluated the occurrence of oxidative stress and changes in cellular redox potential after different periods of hypothermic storage. METHODS: Langendorff-perfused rabbit hearts were subjected to a protocol mimicking each stage of a cardiac transplantation procedure: explantation, storage and reperfusion. Three periods of storage were considered: Group A = 5 hours, Group B = 15 hours, and Group C = 24 hours. Oxidative stress was determined in terms of myocardial content and release of reduced (GSH) and oxidized (GSSG) glutathione, and cellular redox potential as oxidized and reduced pyridine nucleotides ratio (NAD/NADH). Data on mechanical function, cellular integrity and myocardial energetic status were collected. RESULTS: At the end of reperfusion, despite the different timings of storage, recovery of left ventricular developed pressure (46.1+/-7.0, 54.7+/-6.7, and 45.7+/-7.4% of the baseline pre-ischaemic value), energy charge (0.81+/-0.02, 0.81+/-0.02, and 0.77+/-0.01) and NAD/NADH ratio (8.87+/-1.08, 9.39+/-1.72, and 10.26+/-1.98) were similar in all groups (A, B and C). On the contrary, the rise in left ventricular resting pressure (LVRP) and GSH/GSSG ratio were significantly different between Group C, and Groups A and B (p<0.0001, analyzed by Generalized Estimating Equations model for repeated measures, and p<0.05, respectively). CONCLUSIONS: The pathophysiology of myocardial damage during hypothermic storage cannot be considered as a normothermic ischaemic injury and parameters other than energetic metabolism, such as thiolic redox state, are more predictive of functional recovery upon reperfusion.

Animals↗

Induction of functional inducible nitric oxide synthase in monocytes of patients with congestive heart failure. Link with tumour necrosis factor-alpha.

AIMS: We studied the induction of monocytic inducible nitric oxide synthase expression and the tumour necrosis factor-alpha system in patients with congestive heart failure. METHODS AND RESULTS: Forty-three congestive heart failure patients and 15 healthy subjects were studied. Antigenic tumour necrosis factor-alpha and its soluble receptors, measured by ELISA, were increased in chronic heart failure and the increase was related to the clinical severity of the syndrome (tumour necrosis factor-alpha from 8.2+/-5.2 in NYHA class II to 18.2+/-7.2 in class III and 26.9+/-13.2 pg. ml(-1)in class IV, P<0.0001 classes III and IV vs class II; soluble tumour necrosis factor receptor I from 1.0+/-0.2 in class II to 2.3+/-1.1 in class III and 5.5+/-3.2 ng. ml(-1)in class IV, P<0.0001 classes III and IV vs class II; soluble tumour necrosis factor receptor II from 2.7+/-0.7 in class II to 4.9+/-1.9 in class III and 8.4+/-5.0 ng. ml(-1)in class IV, P<0.002 classes III and IV vs class II). Monocytic inducible nitric oxide synthase assessed by Western blot, was expressed only in congestive heart failure patients (13 out of 43). The association among monocytic inducible nitric oxide synthase expression, tumour necrosis factor-alpha system activation, neurohormones and other clinical parameters was studied. The univariate logistic regression showed that inducible nitric oxide synthase expression was strictly associated with NYHA class (P<0.05), antigenic tumour necrosis factor-alpha (P<0.01) and its soluble receptors (P<0.05). The multivariate analysis showed that antigenic tumour necrosis factor-alpha was the only predictor for monocytic inducible nitric oxide synthase expression (P<0.05, RR=2.75, CI 1. 34-5.43). CONCLUSIONS: Inducible nitric oxide synthase is expressed in circulating monocytes of patients with severe congestive heart failure. This phenomenon is linked to the activation of the tumour necrosis factor-alpha system.

Adult↗

Effect of leisure time and working activity on principal risk factors and relative interactions in active middle-aged men.

DESIGN: This study was designed to evaluate, in a cohort of 1039 middle-aged men, the interaction between the duration and intensity of physical activity performed either during leisure time (competitive sports, walking, cycling) or work, and principal coronary disease risk factors. METHOD: A cohort of subjects aged 45-64 years were recruited in 1993. Subjects included both individuals who were physically active and those who were sedentary, and were age-matched. RESULTS: Leisure time physical activity was inversely related to levels of total cholesterol, triglycerides, and fibrinogen, and to diastolic and systolic blood pressure. High-density lipoprotein cholesterol level was directly related to leisure time activity. Working activity, even if strenuous, was not related to risk profile. Leisure time activity did not favorably influence lipid levels in smokers, obese subjects or those with known dyslipidemia. CONCLUSIONS: This study further reinforces the use of continuous diet and drug treatment in dyslipidemic subjects and in smokers, who have to refrain from smoking if they are to benefit fully from the effects of physical activity.

Body Mass Index↗

Trends of congestive heart failure epidemiology: contrast with clinical trial results.

Congestive heart failure (CHF) is an important and growing public health problem and the cause of substantial morbidity and mortality. Its increasing incidence and prevalence may be in part explained by the progressive aging of the world population. The improvement in coronary artery disease and hypertension treatment allows the individuals to lie longer and develop CHF. Indeed, the most common etiology of CHF is coronary artery disease, the leading cause of cardiovascular morbidity and mortality worldwide, and the second cause of CHF is hypertension which is still markedly increasing in developing countries. Estimates of prevalence of CHF are 0.4 to 2% of the general population. The number of hospital admissions for CHF has also been steadily increasing. Half of the patients carrying a diagnosis of CHF will die within 4 years and patients with severe CHF will die within 1 year. At present, there is no evidence that the prognosis of heart failure in the community has changed despite the advances in therapy over the past decades, such as the demonstration that angiotensin-converting enzyme inhibitors and other vasodilators improve the clinical signs and symptoms of patients with CHF, reduce mortality and slow the progression of myocardial dysfunction. Nevertheless, the overall mortality from this condition remains very high. It is possible that the results of the trials have not yet been evidenced in the majority of patients with CHF because the ideal conditions, treatment and follow-up in the trials are not yet widely achieved in the population.

Adult↗

Effect of subcutaneous sumatriptan on head temperature in migraines.

Sumatriptan, a selective 5-hydroxy-triptamine (5-HT1) receptor agonist, has been used recently in the treatment of acute migraine. Some in vitro experiments suggested that sumatriptan has vasoactive properties in vascular beds distinct from cerebral circulation. In view of this we investigated the vascular effects of the standard 6 mg subcutaneous (s.c.) dose of sumatriptan, on the surface areas of the head using thermography, a simple and reliable method for detecting temperature changes. The head temperature of 127 patients (double-blind), 102 migraines (52 during headache attack and 50 headache-free) and 25 healthy control subjects were evaluated using thermography in basal condition and 30, 60, 90, and 120 min after s.c. sumatriptan injection of placebo. During the entire observation period systemic blood pressure (SBP), heart rate (HR) and continuous electrocardiogram (ECG) were detected automatically. A significant head temperature decrease was observed after s.c. sumatriptan administration, in both healthy controls and migraine subjects; placebo administration did not show any change of temperature. In migraine patients during headache attack, head temperature reduction corresponded to the relief of headache symptoms. This vasoconstrictor effect detected with thermography is not isolated to cranial circulation but it is also systemic. In fact, we observed a significant increase (p < 0.05) in both systolic and diastolic systemic blood pressure. No significant changes in heart rate and ECG abnormalities were otherwise detected. These findings suggest that sumatriptan is effective in the treatment of migraine attack, but it must be used with caution in migraines with concomitant hypertension.

Adult↗

Succinate sumatriptan evaluation by Doppler echocardiography in patients with migraine.

Recent reports show that sumatriptan administration increases blood pressure and vascular resistance both in systemic and pulmonary circulation. This study was performed to evaluate by echo-Doppler technique the hemodynamic effects of subcutaneous sumatriptan administration. Forty-one migraine subjects (26 males, 15 females), mean age 36 +/- 2 years (range 36-39 years), and 20 healthy control subjects (14 males, six females), mean age 36 +/- 2 years (range 36-39 years) were randomized (double-blind) to receiving sumatriptan (group A) or placebo (group B). After a 2-week complete pharmacological washout, clinical examination, electrocardiogram, and Doppler echocardiography were performed at baseline, 15, 30, 45, and 60 min after sumatriptan or placebo administration. No significant differences were found between the two groups regarding Doppler echocardiographic parameters (aortic integral, pulmonary integral, end-systolic and end-diastolic diameters) and heart rate; only a slight but not significant increase in arterial blood pressure was observed in group A. Our data show that succinate sumatriptan can be used with safety in patients without hypertension and other cardiovascular disease.

Adult↗

Sulodexide versus calcium heparin in the medium-term treatment of deep vein thrombosis of the lower limbs.

Thirty adult patients with distal, monolateral deep vein thrombosis of the lower limbs were randomly treated for sixty days either with subcutaneous Ca-Heparin or with Sulodexide, administered IM for ten days and orally for fifty days. The thrombus accretion above the knee, the venous pressures of the affected leg, the clinical symptomatology, and some laboratory coagulative tests were monitored throughout the administration period. Local tolerability of the two treatments was also evaluated. The two applied treatments evidenced a net antithrombotic activity, preventing thrombus accretion above the knee, improving with the same efficacy the venous pressures in the affected legs, and similarly reducing clinical symptoms, with a quick and statistically significant trend toward normalization. Blood fibrinogen was significantly lowered by both drugs, while only Ca-heparin yielded a prolongation of activated partial thromboplastin time. Local tolerability of treatments was better for the mainly oral Sulodexide administrations, while subcutaneous Ca-heparin often induced small, though transient, hematomas.

Adult↗

Central obesity and hypertension: the role of plasma endothelin.

Hypertension and central obesity are two conditions closely linked, but the mechanisms responsible for obesity-associated hypertension are still unclear. In the last few years, several studies addressed the role of endothelin-1 (ET-1) in the development and maintenance of hypertension. This study was designed to evaluate plasma ET-1 in normotensive and hypertensive central obese subjects compared with a lean healthy group. Our final goal was to analyze the relationship between plasma ET-1, blood pressure, and left ventricular structure and function in central obese subjects (both normotensives and hypertensives). ET-levels have been assessed by the radioimmunoassay method in 20 lean normotensives and in 57 central obese subjects; 30 of them were hypertensives and 27 of them were normotensives. Twenty-four-hour mean blood pressure (MBP/24 h) by noninvasive ambulatory blood pressure monitoring, left ventricular mass/ height (LVM/H), and left ventricular ejection fraction (LVEF) by echocardiography and peak filling rate (PFR) by radionuclide study were also measured. ET levels were significantly (P < .05) higher in obese hypertensives and obese normotensives than in lean normotensives. In addition, ET levels were significantly (P < .05) higher in obese hypertensives than in obese normotensives. ET were directly related to LVM/ H (r = 0.86; P < .001) and MBP/24 h (r = 0.48; P < .009) but only in obese hypertensives. Multiple regression analysis indicated that ET-1 plasma levels remain an independent predictor of MBP/ 24 h and LVM/H also when age was included in the analysis. These data suggest that obesity-associated hypertension is characterized by an endothelial dysfunction that may contribute to the higher cardiovascular risk detectable in these patients.

Adult↗