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Biomedical subjects

M Salvetti

Publications and source records attributed to M Salvetti.

At least 73 records · Page 4Linked to original sources
PubMed1996

Involvement of the limbic system in multiple sclerosis patients with depressive disorders.

This study investigates the relationship between depression and both anatomic and cerebral blood flow abnormalities in multiple sclerosis (MS) patients. Ten nondepressed MS patients were compared with 10 depressed MS patients matched for age, sex, and functional disability. Both groups were evaluated by means of neuropsychological tests, magnetic resonance imaging, and single-photon emission tomography imaging. There was no difference between the two groups with regard to the global cognitive score. Magnetic resonance imaging data showed no significant differences in the number, side, location, and area of the demyelinating lesions between the two groups; however, regional cerebral blood flow asymmetries in the limbic cortex did distinguish the two groups. Analysis of variance showed a significant effect of depression on the perfusion asymmetries in the limbic cortex. Finally, perfusion asymmetries in limbic cortex significantly correlated with depression test scores. Our findings suggest that depression in MS patients could be induced by a disconnection between subcortical and cortical areas involved in the function of the limbic system.

Adult↗
PubMed1996

The immune response to mycobacterial 70-kDa heat shock proteins frequently involves autoreactive T cells and is quantitatively disregulated in multiple sclerosis.

Heat shock proteins (HSP) are the most conserved molecules known to date that may also function as immune targets during infection. Hence, theoretically there is a high chance of cross-reactive responses to epitopes shared by host and microbe HSP. If not properly regulated, these responses may contribute to the pathogenesis of autoimmune disease. To determine if immune responses to HSP could contribute to the pathogenesis of multiple sclerosis, we raised T lymphocyte lines specific for the purified protein derivative of Mycobacterium tuberculosis (PPD) from patients with multiple sclerosis, patients with tuberculosis and from healthy individuals. These lines were then screened for their proliferative response to a M. tuberculosis 70-kDa heat shock protein (M.tb.HSP70). The relative frequency of the recognition of highly conserved sequences of M.tb.HSP70 compared to variable ones was also assessed by mapping experiments on those PPD specific T lymphocyte lines which also recognized the mycobacterial 70-kDa heat shock protein. In patients with multiple sclerosis, we observed a significantly higher estimated frequency of PPD-specific T lines responding to M.tb.HSP70 compared to healthy individuals and patients with tuberculosis. Furthermore, mapping experiments using recombinant proteins representing mycobacterial and human HSP70 sequences and a panel of synthetic peptides encompassing the whole sequence of Mycobacterium leprae HSP70, showed that the response to conserved epitopes of HSP70 is a frequent event in each of the three conditions studied, often leading to the cross-recognition of microbial and human sequences. These findings implicate the 70-kDa heat shock proteins as potential autoantigens in multiple sclerosis.

Adult↗
PubMed1996

Cardiac and vascular structural changes. Prevalence and relation to ambulatory blood pressure in a middle-aged general population in northern Italy: the Vobarno Study.

The aims of this study were to determine the prevalence of structural changes in the carotid arteries and heart and the correlation between these changes and the commonly recognized cardiovascular risk factors in the general population. Structural changes in the carotid arteries were defined as the intima-media thickness of the artery measured by B-mode ultrasound. Changes in the heart were defined as left ventricular mass index (LVMI) measured by echocardiography. LVMI values greater than 134 g/m2 in men and greater than 110 g/m2 in women were considered abnormal, indicating the presence of left ventricular hypertrophy. Blood pressure (BP) was measured in the clinic setting with a mercury sphygmomanometer and by 24-hour noninvasive ambulatory monitoring. Hypertension was defined as a sustained systolic BP greater than or equal to 160 mm Hg and/or diastolic BP increase greater than or equal to 95 mm Hg. The study population consisted of 225 subjects (107 women and 118 men) 48 to 64 years old. Prevalence of intima-media thickening (intima-media thickness > 1 mm) was 11% in normotensive subjects and 44% in hypertensive subjects. The presence of plaque (wall thickening with either mineralization or focal protrusion in the lumen at least 50% greater than the surrounding wall, usually > 2 mm) was observed in 35% of normotensive subjects and 44% of hypertensive subjects. The prevalence of left ventricular hypertrophy was 13% in normotensive subjects and 19% in hypertensive subjects. Intima-media thickness in the common and bifurcation segments of carotid arteries correlated well with LVMI (r = .20 and r = .19, respectively; P < .01). Intima-media thickness and LVMI were both positively related to 24-hour monitored BP (P < .01). However, in the multivariate analysis, body mass index (P = .027), sex (P < .001), and 24-hour mean BP (P = .025) were the most significant determinants of LVMI, whereas carotid artery intima-media thickness was found to be associated best with age (P < .001), cigarette smoking (P = .009), serum cholesterol (P = .025), serum glucose (P = .038), and nighttime systolic BP (P = .006). Logistic regression analysis confirmed the association between the presence of plaque and age (P < .001), nighttime systolic BP (P < .05), and cigarette smoking (P < .05); a negative association between plaque and the decrease in mean systolic BP daytime to nighttime was also observed (P < .001). In conclusion, in a general population of unselected middle-aged subjects, carotid wall thickness and LVMI were associated with each other and related to 24-hour BP levels although the major determinants of carotid wall and cardiac structure were different.

Aged↗
PubMed1996

Angiotensin II type 1 receptor A/C1166 polymorphism. Relationships with blood pressure and cardiovascular structure.

The angiotensin II type 1 (AT1) receptor has a key role in mediating the vasoconstrictor and growth-promoting effects of angiotensin II. It has been reported that a polymorphism of the AT1 receptor gene (an A/C transversion at position 1166) may be associated with cardiovascular phenotypes, such as arterial blood pressure and aortic stiffness, that underlie a condition of increased cardiovascular risk. We examined a sample of 212 subjects randomly selected from a general population in northern Italy to investigate the role of AT1 receptor gene polymorphism, in the regulation of blood pressure and cardiovascular growth. We measured blood pressure (both clinic and 24-hour ambulatory recording), left ventricular mass (echocardiography), and carotid artery wall thickness (B-mode ultrasound); we assessed the AT1 receptor genotype by polymerase chain reaction and allele-specific oligonucleotide hybridization. Blood pressure values were lower in CC homozygotes than in heterozygotes and AA homozygotes; the difference was statistically significant for clinic measurements (mean difference for mean blood pressure, -6.6 mm Hg, P = .01; 95% confidence interval, -1.6 to -11.7 mm Hg) but not for ambulatory blood pressure measurements. CC homozygotes also presented a lower incidence of a positive family history of hypertension (P = .027). No statistically significant differences among AT1 receptor A/C1166 genotypes were observed for left ventricular mass or carotid artery wall thickness. We conclude that the present study does not support a major role of the AT1 receptor gene A/C1166 polymorphism as a marker of conditions associated with increased cardiovascular risk.

Blood Pressure↗
PubMed1996

Persistence of left ventricular hypertrophy is a stronger indicator of cardiovascular events than baseline left ventricular mass or systolic performance: 10 years of follow-up.

OBJECTIVE: Left ventricular hypertrophy (LVH) and depressed left ventricular performance have been shown to be associated to an adverse prognosis in hypertensive patients. It has not been established, however, whether, during chronic antihypertensive treatment, the increased cardiovascular risk is more strictly related to the presence of LVH or of a low left ventricular performance. DESIGN AND METHODS: A total of 215 patients with uncomplicated hypertension (129 males, 86 females; age range 18-70 years, mean +/- SD 45 +/- 11) underwent an echocardiographic evaluation of left ventricular anatomy and function. In 151 patients (87 males, 64 females; age range 18-70 years, mean 45 +/- 10.4) the echocardiogram was repeated on average 10 +/- 1 years after the initial study. The presence of LVH (left ventricular mass index > 134 g/m2 in males and 110 g/m2 in females) and the midwall left ventricular shortening/end-systolic stress relationship were prospectively analysed as predictors of cardiovascular non-fatal events (n = 23) in patients who were seen at follow-up. RESULTS: The incidence of non-fatal cardiovascular events was greater in patients with LVH (n = 17, P < 0.0001) and in those with a lower midwall performance (n = 14, P < 0.01) at baseline. At follow-up, the incidence of non-fatal cardiovascular events was significantly greater in patients without a reduction in the left ventricular mass index, after adjusting for traditional risk factors (relative risk 3.52 versus 1.38 in patients with persistence and regression of LVH, respectively; P < 0.01). The baseline midwall fractional shortening was lower in patients with both persistence or regression of LVH (analysis of variance, P < 0.0001) than in patients with a normal left ventricular mass index. In logistic analysis, the left ventricular mass index at follow-up and age were independent determinants of non-fatal cardiovascular events (P < 0.001); without the left ventricular mass index at follow-up, this analysis showed that age, systolic blood pressure at follow-up and baseline midwall fractional shortening were independent determinants of non-fatal cardiovascular events. CONCLUSIONS: Our results suggest that lack of regression of LVH is a stronger indicator of cardiovascular risk than a depressed baseline midwall left ventricular performance.

Adolescent↗
PubMed1995

Angiotensin-converting enzyme I/D polymorphism and arterial wall thickness in a general population. The Vobarno Study.

BACKGROUND: It has been reported that the D allele of an insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene is associated with conditions of increased cardiovascular risk, including left ventricular hypertrophy. METHODS AND RESULTS: Considering that a genetically determined overactivity of the renin-angiotensin system may influence cardiac as well as vascular growth, we investigated possible relations between ACE I/D genotype and carotid artery wall thickness (B-mode ultrasound) in 199 subjects, 50 to 64 years old, sampled from the general population of Vobarno, a small town in northern Italy. ACE DD genotype was associated with significantly higher common carotid artery intima-media thickness (P = .003). The occurrence of carotid atherosclerotic plaques was similar in the different genotypes. There was no association of the ACE I/D genotype with blood pressure values (either casual of 24-hour ambulatory monitored). CONCLUSIONS: ACE DD genotype may be considered a risk factor for the development of common carotid intima-media thickening in our study population.

Alleles↗
PubMed1995

Clinical and MRI assessment of disease activity in patients with multiple sclerosis after influenza vaccination.

We investigated the possible effects of influenza vaccination on disease activity in multiple sclerosis (MS). Six patients were evaluated clinically during the year preceding and the year following influenza vaccination. Gadolinium-enhanced magnetic resonance imaging (Gd-MRI) was performed one day before and at days 15 and 45 after vaccination. Cumulatively, we did not observe increases in clinical or MRI disease activity following vaccination, with the exception of one case. This was the patient with the highest clinical disease activity during the year preceding vaccination. These results support and supplement previous observations, indicating that influenza vaccination is a safe procedure in multiple sclerosis. Nevertheless, it should be used with caution in patients with active/progressing disease.

Adult↗
PubMed1995

Polyurethane-coated, self-expandable biliary stent: an experimental study.

RATIONALE AND OBJECTIVES: We describe a self-expanding metallic biliary Gianturco-Rösch stent coated with polymeric material. The coating was designed to prevent the growth of neoplastic and reactive tissue within the biliary ducts. METHODS: The stents were coated with a solvent-casting technique, which consists of dissolving polyurethane (polyether urethane or polycarbonate urethane) pellets in a solvent (dimethylacetamide), dipping the stent in the solution, and completely evaporating the solvent. In vitro mechanical characterization of the stent was performed to determine the adhesion of the coating to the metallic cage, the best introducer caliber for implantation of the device, and the relationship between the stent's diameter and radial stress. RESULTS: Reports in the literature on the biostability of polycarbonate urethane compared with polyether urethane prompted us to use the former material to coat the stents. The solvent technique gives a smooth internal surface of the stent wall, leaving in relief the coated structure of the stent on the external surface. The functional tests demonstrated that the coating did not compromise the original characteristics of the stent in terms of self-expandability, axial flexibility, and increased radial rigidity of the device. CONCLUSION: Functional tests verified coating stability and device handling, which are the first steps toward in vivo experimentation.

Bile Ducts↗
PubMed1995

Arterial spontaneous rhythmic contractile activity in humans and rats: spectral analysis and regulatory mechanisms.

OBJECTIVE: Many experimental observations have demonstrated the presence of spontaneous cyclic vasomotor activity (CVA) in large and small arteries. This study aimed to evaluate the characteristics of spontaneous CVA in rat and human resistance arteries, and to investigate its possible interference with the evaluation of sympathetic activity by means of spectral analysis of blood pressure in vivo. DESIGN AND RESULTS: In study 1 we examined small mesenteric arteries of spontaneously hypertensive rats and Wistar-Kyoto rats, as well as small omental arteries of normotensive subjects and hypertensive patients (Mulvany and Halpern technique). CVA was enhanced by the agonists of nitric oxide release, and was abolished by the inhibitors of nitric oxide or cyclic GMP synthesis. A potassium channel, which is barium- and zinc-sensitive and tetraethylammonium-insensitive, seems to play a crucial role in the genesis of CVA. In rats and in humans the frequency of CVA fell exactly in the frequency band ('low frequencies') of power spectral analysis of blood pressure usually considered to be an 'index of sympathetic activity'. In study 2, a power spectral analysis of blood pressure variability before and after intra-arterial infusion of noradrenaline or acetylcholine was performed in 18 patients with mild-to-moderate hypertension. The absolute and normalized spectral power of the low-frequency systolic blood pressure peak increased remarkably after noradrenaline and acetylcholine infusion, while its central frequency shifted from 0.10 Hz to approximately 0.06 Hz, exactly the frequency of CVA observed in vitro. CONCLUSIONS: A potassium channel appears to be involved in the genesis of CVA. Also, CVA might contribute to the blood pressure variability independently of the autonomic nervous system activity, and thus probably plays a role in the genesis of the low-frequency peak in the rat and in humans.

Acetylcholine↗
PubMed1995

Association of change in left ventricular mass with prognosis during long-term antihypertensive treatment.

OBJECTIVE: The aim of the present study was to assess the prognostic value of changes in left ventricular hypertrophy in hypertensive patients with time. DESIGN: Two hundred and fifteen uncomplicated hypertensive patients underwent a high-quality baseline echocardiogram for left ventricular anatomy evaluation and in 151 of those patients the echocardiographic examination was repeated 10 +/- 1.4 years after the initial study. METHODS: Left ventricular mass index changes were evaluated, in relation to the incidence of non-fatal cardiovascular events, adjusted for traditional cardiovascular risk factors. RESULTS: According to the presence or absence of left ventricular hypertrophy (left ventricular mass index > 134 g/m2 in men and > 110 g/m2 in women) at baseline and at the end of follow-up study, patients were divided into four groups: with normal left ventricular mass at both examinations (n = 78), with regression of left ventricular hypertrophy (n = 32), with persistence of left ventricular hypertrophy (n = 34) and with hypertrophy development (n = 7). After adjustment for traditional cardiovascular risk factors, the cumulative incidence of non-fatal cardiovascular events was significantly higher in the group of patients without regression of left ventricular hypertrophy. Cox survival analysis showed the presence of left ventricular hypertrophy at the end of follow-up study to be the most important factor related to cardiovascular events. CONCLUSIONS: The present findings strongly indicate that the lack of decrease or the increase of left ventricular mass after antihypertensive treatment can be associated with a higher risk for cardiovascular events, which is significantly reduced and almost normalized by complete regression of left ventricular hypertrophy.

Adolescent↗
PubMed1995

Relationship between sympathetic nervous system activity, baroreflex and cardiovascular effects after acute nitric oxide synthesis inhibition in humans.

OBJECTIVE: To examine the cardiovascular effects of acute systemic nitric oxide synthesis inhibition in humans in relation to the possible involvement of changes in sympathetic nervous system activity or in the baroreceptor reflex. DESIGN: Placebo or NG-monomethyl-L-arginine (250 mg by intravenous infusion for 5 min) was administered to seven healthy male volunteers according to a random, double-blind sequence. METHODS: Blood pressure and heart rate were measured non-invasively using a Finapres device from 20 min before to 80 min after starting infusion; beat-to-beat variability of blood pressure, pulse interval and systolic blood pressure and pulse interval covariation were assessed by means of spectral and sequence analysis methods. Under basal conditions and 15 min and 60 min after infusion, we measured stroke volume and indices of cardiac systolic and diastolic function by echocardiography, forearm blood flow by strain-gauge venous occlusion plethysmography, and plasma catecholamine levels. RESULTS: Compared with placebo, administration of NG-monomethyl-L-arginine caused a transient increase in blood pressure and reduction in heart rate. Stroke volume and indices of cardiac function did not change significantly, whereas cardiac index and forearm blood flow were significantly reduced after 15 min. Spectral analysis of blood pressure and pulse interval showed a significant reduction of power spectral density in the low frequencies (0.03-0.15 Hz) that persisted 60 min after infusion. The plasma noradrenaline level was significantly reduced after 15 min. No change in baroreflex engagement or sensitivity was detected by the cross-spectral or the sequence method. CONCLUSIONS: Acute systemic nitric oxide synthesis inhibition transiently increases blood pressure and reduces heart rate and cardiac index. The acute hypertensive response to NG-monomethyl-L-arginine is dependent neither on sympathetic nervous system activity, which is probably reduced as a consequence of baroreceptor reflex activation, nor on baroreceptor reflex sensitivity, which is not impaired.

Adult↗
PubMed1995

A controlled study of potential risk factors preceding exacerbation in multiple sclerosis.

A wide variety of potential risk factors for acute exacerbations in multiple sclerosis were evaluated in a one year case-control study. Eighty nine consecutive patients with clinically definite multiple sclerosis and relapsing remitting course presenting with a relapse between January and December 1992 were compared with patients matched for age, sex, and degree of disability, who did not experience clinical exacerbations during the same period. Only potential risk factors occurring in the three months preceding the interview were considered patients. Relapsing patients reported no significant increase in the frequency of any risk factor in the three month period before exacerbation compared with the control group. These results suggest that most relapses are not preceded by the conditions commonly considered as risk factors.

Adolescent↗
PubMed1995

Media: lumen ratio in human small resistance arteries is related to forearm minimal vascular resistance.

BACKGROUND: For the evaluation in humans of structural alterations in resistance arteries, most studies have used an indirect index, the measurement of minimal vascular resistance (mean blood pressure divided by maximal postischaemic blood flow) in suitable vascular beds. A sensitive and specific micromyographic technique was recently made available for the study of human small resistance arteries. Whether a correlation really exists between results obtained with the two techniques has not yet been investigated. OBJECTIVE: To evaluate both forearm minimal vascular resistance and media:lumen ratio of omental or subcutaneous small arteries in normotensive subjects and hypertensive patients. DESIGN AND METHODS: Thirty-four individuals were included in the study (age range 35-74 years; 24 hypertensive, 10 normotensive). Twenty-five had elective abdominal surgery and nine hypertensive patients had a gluteal biopsy. Omental and subcutaneous small arteries were dissected and mounted on a wire micromyograph (Mulvany's technique), and media:lumen ratio and media thickness were measured. The dose-response curve to noradrenaline was constructed at cumulative concentrations from 3 x 10(-9) to 3 x 10(-5) mol/l. Venous occlusion plethysmography was used to measure blood flow in the forearm, and minimal vascular resistance was calculated from mean blood pressure and postischaemic maximal blood flow (13 min ischaemia plus exercise). RESULTS: A statistically significant correlation was found between media:lumen ratio and minimal vascular resistance (r = 0.74, P < 0.001) as well as between media:lumen ratio and systolic (r = 0.44, P < 0.01) and diastolic (r = 0.38, P < 0.05) blood pressures. Similar correlations were observed between media thickness and systolic and diastolic blood pressures. Small arteries from hypertensive patients had a significantly increased reactivity to noradrenaline (by analysis of variance) compared with those from normotensive subjects, in terms of wall tension but not of active media stress. CONCLUSIONS: The present study demonstrated that the media:lumen ratio of small resistance vessels is significantly related to forearm minimal vascular resistance, suggesting that direct and indirect evaluations of vascular morphology will give similar results.

Adult↗
PubMed1995

Gamma delta T cell receptor analysis supports a role for HSP 70 selection of lymphocytes in multiple sclerosis lesions.

BACKGROUND: Interactions between gamma delta T cells and heat shock proteins (HSP) have been proposed as contributing factors in a number of diseases of possible autoimmune etiology but definitive evidence to support this hypothesis has been lacking. In multiple sclerosis (MS), a chronic inflammatory neurologic disease, HSP and gamma delta T cells are known to colocalize in brain lesions. Analysis of T cell receptor (TCR) gene usage in these lesions has detected evidence of clonality within both the V delta 2-J delta 1 and V delta 2-J delta 3 populations of gamma delta T cells. In our own studies, using direct sequence analysis, a dominant V delta 2-J delta 3 TCR sequence was found in 9 MS brain samples, suggesting a response to a common antigen. In this report, we have examined gamma delta T cell receptor gene usage in MS peripheral blood T cell lines selected for reactivity to HSP 70. MATERIALS AND METHODS: TCR rearrangement patterns for V delta 2-J delta 1 and V delta 2-J delta 3 were studied using the polymerase chain reaction (PCR) and a direct sequencing technique in populations of peripheral blood mononuclear cells (PBMC) cultured with Mycobacterium tuberculosis (M. tuberculosis) purified protein derivative (PPD) and then selected for reactivity to a 70-kD heat shock protein (HSP70). Cells were obtained from health donors, patients with MS, and patients with tuberculosis (TB). PCR products were subjected to direct sequence analysis to look for evidence for clonality within these T cell lines and to define the sequence of the V-D-J (CDR3) region of the TCR. RESULTS: In freshly isolated PBMC, both V delta 2-J delta 1 and V delta 2-J delta 3 gene rearrangement patterns were detected, whereas in HSP70+ T cell lines the predominant delta chain rearrangement pattern was V delta 2-J delta 3. Direct sequence analyses indicated that in cells reactive with HSP70 the V delta 2-J delta 3 sequences were usually oligoclonal and used D delta 3 exclusively. In four of four MS and two of three TB patients, the oligoclonal sequences in the HSP70+ T cell lines were identical to one another and to a dominant sequence previously detected in MS brain lesions. In two of three HSP70+ T cell lines from healthy controls, the oligoclonal sequences differed from those found in both groups of patients but were identical to one another except for a small region of heterogeneity in the second N region. In contrast, in freshly isolated PBMC or in PPD+HSP70- T cell lines, the V delta 2-J delta 3 gene rearrangement patterns were usually polyclonal and dominant sequences were rarely identified. CONCLUSIONS: These results support the conclusion that a subpopulation of gamma delta T cells in MS lesions are responding to HSP 70 and that non-CNS-specific antigens contribute to the pathogenesis of MS.

Amino Acid Sequence↗
PubMed1995

Effects of antihypertensive therapy with angiotensin converting enzyme inhibitors or calcium antagonists on spontaneous cyclic vasomotor activity in small resistance arteries of spontaneously hypertensive rats.

OBJECTIVE: Spontaneous cyclic vasomotor activity can occur in small resistance arteries in vitro after precontraction with a vasoconstrictor. Calcium and potassium channels and nitric oxide synthesis or release seem to be involved in the genesis of this vasomotor activity. We therefore investigated the effects of chronic antihypertensive therapy with calcium antagonists and angiotensin converting enzyme (ACE) inhibitors on the amplitude and frequency of cyclic vasomotor activity in vitro in spontaneously hypertensive rats (SHR). MATERIALS AND METHODS: SHR were treated with fosinopril at 25 mg/kg per day or lacidipine at 10 mg/kg per day or nitrendipine at 30 mg/kg per day, from the age of 4 to 12 weeks. Data were compared with those obtained in untreated SHR and Wistar-Kyoto (WKY) rats. Half the rats were killed at 13 weeks of age, and the remaining half were killed at 38 weeks of age. The mesenteric small resistance arteries were dissected, mounted on a micromyograph and then contracted submaximally with noradrenaline. Acetylcholine was then added to the organ bath. RESULTS: More than 50% of the vessels showed cyclic vasomotor activity. The frequency and amplitude of this activity were greater in SHR than WKY rats after noradrenaline and after acetylcholine. At 13 weeks of age (but not at 38 weeks of age), treatment with a calcium antagonist (either lacidipine or nitrendipine) significantly reduced the frequency and amplitude of the vasomotor activity, probably by interfering with calcium entry. No change was observed after fosinopril. CONCLUSIONS: Antihypertensive treatment with different drugs may affect cyclic vasomotor activity differently, probably by interfering with cellular mechanisms involved in its genesis. The effects of calcium antagonists on cyclic vasomotor activity are still present after short-term but not after long-term treatment withdrawal.

Angiotensin-Converting Enzyme Inhibitors↗