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Biomedical subjects

M Salvetti

Publications and source records attributed to M Salvetti.

At least 55 records · Page 3Linked to original sources
PubMed1998

Relations between cardiac and vascular structure in patients with primary and secondary hypertension.

BACKGROUND: Data on cardiac and vascular structure in secondary hypertension are generally scarce, and no data on the interrelations between cardiac mass and structural characteristics of the vessel wall, both in large and in small resistance arteries, are presently available. OBJECTIVES: The aim of this study was to investigate the relation between structural changes in subcutaneous small arteries, left ventricular mass and wall thickness of the common carotid artery in patients with primary and secondary hypertension. METHODS: Seventy-four subjects were included in the study: 11 patients with pheochromocytoma, 14 with primary aldosteronism (PA), 19 with renovascular hypertension (RVH), 18 with essential hypertension (EH) and 12 normotensive (NT) control subjects. All subjects were submitted to a biopsy of subcutaneous fat. Morphologic characteristics of subcutaneous small resistance arteries (relaxed diameter <300 microm) were directly evaluated using a micromyographic technique. All subjects were submitted to calculation of left ventricular mass index (LVMI) and common carotid artery intima-media thickness (CCIMT), using ultrasound technique. RESULTS: The correlation coefficients between the media to lumen ratio in subcutaneous small arteries (M/L) and LVMI or between M/L and CCIMT were closer in RVH than in pheochromocytoma, EH or NT; in PA the correlation coefficients were slightly less close than those in RVH. An excess prevalence of carotid plaques in RVH was observed. CONCLUSIONS: A close relation between small resistance artery morphology and cardiac or carotid artery structure may be observed in those hypertensive patients in whom the renin-angiotensin-aldosterone system is activated. In constrast, in NT, EH and pheochromocytoma no significant correlation between M/L and LVMI or CCIMT was observed.

Arterioles↗
PubMed1998

A restricted T cell response to myelin basic protein (MBP) is stable in multiple sclerosis (MS) patients.

The close resemblance of MS to the animal model experimental autoimmune encephalomyelitis (EAE) has provided compelling data sustaining a pathogenic role of circulating T cells reactive against MBP. T cell antigen receptor (TCR) usage in EAE is commonly considered restricted; nevertheless, dynamic changes of TCR usage correlate with the course of EAE, resulting in a limited repertoire during early stages of disease activity followed by the recruitment of other T cells reactive against new determinants. Although a broader TCR repertoire mediates the response to MBP in humans, a restricted intraindividual heterogeneity may occur in some MS patients. In the present study we characterize the response to MBP in MS subjects with relapsing remitting disease from two sampling time points 12 months apart. MBP-specific T cell lines (TCL) were first generated from eight MS individuals and two healthy subjects. New TCL were obtained after 12 months from one control and three MS patients whose response, at the first time point, was directed against a single epitope. Interestingly, these three subjects had a stable and mild disease. Few TCL obtained at two time points from the MS individuals recognized the same immunodominant epitope and shared identical TCR Vbeta sequences. In the control we could not detect a restriction of the repertoire. These findings suggest that in some MS patients with benign disease a predominant T cell response to a single determinant may be detectable at different moments and is mediated by clonally expanded populations.

Adult↗
PubMed1998

Reduction of cardiovascular structural changes by nifedipine GITS in essential hypertensive patients.

The aim of this study was to evaluate the effect of the calcium antagonist Nifedipine GITS in a double-blind, randomized comparison with the diuretic hydrochlorothiazide (HCTZ) on reduction of left ventricular (LV) mass and minimal vascular resistance in a group of essential hypertensives with left ventricular hypertrophy (LVH). The effects on blood pressure and on echocardiographic LV functional parameters were also analysed. After two months of randomized treatment with Nifedipine GITS or HCTZ, if diastolic blood pressure was > 90 mmHg, a combination of the two drugs was given and was continued for 24 weeks. M-mode, 2D-guided echocardiography was used to measure LV mass index (LVMI) according to the "Penn convention". Minimal vascular resistance was measured in the forearm, from arterial pressure and maximal blood flow, using a strain gauge plethysmography. All examinations were performed before and after 8 and 24 weeks of treatment. Changes in LVMI were analysed at 8 weeks and at 24 weeks in patients receiving monotherapy ("according to protocol" analysis), and also at the end of treatment in patients taking Nifedipine or HCTZ monotherapy or the combination of the two drugs ("intention to treat" analysis). Both Nifedipine and HCTZ significantly reduced systolic and diastolic blood pressure (p < 0.001), without any significant difference between the two drug treatments. Heart rate was not significantly modified by either treatment. A progressive decrease in LVMI was observed after 8 and 24 weeks of treatment with Nifedipine monotherapy (ANOVA, p = 0.03), while the decrease in LVMI during HCTZ treatment did not progress further at 24 weeks (ANOVA, p = 0.49). A significant reduction of minimal vascular resistance was observed in patients treated with Nifedipine GITS monotherapy (ANOVA, p = 0.001), but not in the HCTZ group (ANOVA, p = 0.06). Comparison of changes of forearm minimal vascular resistance, considering baseline values, could demonstrate a greater effect during Nifedipine monotherapy as compared to HCTZ monotherapy. In conclusion, in a group of hypertensive patients with LVH, treatment for 24 weeks with Nifedipine GITS alone or in combination with HCTZ induced a significant reduction in LVMI and of forearm vascular structural changes, as evaluated by minimal vascular resistance. The decrease of minimal vascular resistance was significantly greater in patients treated with Nifedipine monotherapy, as compared to those given HCTZ.

Adult↗
PubMed1998

Development of neutralizing antibodies in patients with relapsing-remitting multiple sclerosis treated with IFN-beta1a.

Sixty-eight patients with relapsing-remitting multiple sclerosis (RRMS) were treated with 3 million or 9 million i.u. of recombinant interferon-beta1a (recIFN-beta1a) s.c. three times a week for 2 years. Their sera were tested for antibodies neutralizing the IFN (NAb) in a bioassay. Sera with titers > or = 1:20 were considered positive. We detected NAb in 3.2%, 13.8%, and 15.9% of the patients in sera obtained at 3, 6, and 24 months, respectively. The incidence was not related to the IFN dose. Interestingly, during the 6 month baseline period before the start of the study, relapse rates, baseline disability, and the volume of lesions on T2-weighted images were significantly higher in patients who developed NAb during treatment. Because of interpatient variability, no definitive relationship was observed between NAb formation and loss of clinical or magnetic resonance imaging (MRI) response.

Adolescent↗
PubMed1998

Various ways of calculating echocardiographic left ventricular mass and their relative prognostic values.

OBJECTIVE: To compare the calculations of left ventricular mass according to thick-wall [American Society of Echocardiography (ASE) and Penn convention] and thin-wall (Wikstrand formula) models. METHODS: We have reexamined the data from the cross-sectional study on the general population sample of Vobarno and from a prospective longitudinal study of hypertensive patients assessing the prognostic significance of changes in left ventricular mass during a follow-up period of 10 years on average (Brescia population). RESULTS: For the Vobarno and Brescia populations, we found a close relationship between values of left ventricular mass calculated by using a thin-wall ellipsoidal model (Wikstrand formula) and those calculated using a thick-wall model with Penn convention or ASE left ventricle measurements (r = 0.99, for both the Vobarno and Brescia populations). Highest values of Penn left ventricle mass were slightly underestimated by use of the thin-wall formula. The numbers of nonfatal cardiovascular events and the relative risks, evaluated by Cox proportional hazard models for 151 patients seen at follow-up did not differ for patients with persistence of left ventricular hypertrophy (LVH), those with regression of LVH, and those with normal left ventricle mass, both at baseline and at follow-up, when these different ways of measuring left ventricle mass and partition values for LVH were used. CONCLUSIONS: The calculation of left ventricle mass according to the ASE recommendations or to the Penn convention, both of which are based on the assumption that the left ventricle can be represented by a prolate ellipsoid with both the internal and external long axes twice the short axis, produces results similar to those obtained using an alternate formula for the calculation of left ventricle mass, considering wall thickness constant around the ellipsoidal cavity. The cardiovascular risk stratification, in relation both to baseline left ventricular mass and to its change during long-term antihypertensive treatment, does not differ significantly among the results of these three different calculations.

Antihypertensive Agents↗
PubMed1998

Structural association between the carotid artery and the left ventricle in a general population in Northern Italy: the Vobarno study.

OBJECTIVE: To evaluate the interrelationships between structural alterations in the carotid arteries and left ventricular geometric patterns in a middle-aged general population. DESIGN AND METHODS: We studied 223 untreated subjects (106 females, 117 males; aged 48-64 years) living in a small town in Northern Italy (Vobarno, Brescia), using a cross-sectional design. The left ventricular mass index was assessed by echocardiography, while the intima-media thickness and the occurrence of plaque were evaluated by ultrasound. Blood pressure was determined by clinic measurements and by 24 h noninvasive ambulatory blood pressure monitoring. RESULTS: According to the presence of left ventricular hypertrophy (left ventricular mass index > 50 g/m2.7 in males and > 47 g/m2.7 in females) or concentric left ventricular remodelling (normal left ventricular mass index and relative wall thickness > 0.42), the subjects were divided into four groups: 124 subjects with normal left ventricular geometry, 73 subjects with left ventricular hypertrophy (55 with eccentric and 18 with concentric hypertrophy) and 26 subjects with concentric remodelling. The common carotid intima-media thickness and cross-sectional area were significantly greater in the subjects with concentric left ventricular hypertrophy (analysis of variance, P< 0.05) than in those with normal left ventricular geometry. A significantly higher number of plaques was observed in subjects with concentric and eccentric left ventricular hypertrophy. CONCLUSIONS: In a general population of unselected middle-aged subjects, the presence of concentric left ventricular hypertrophy was associated with an increase in intima-media thickness and with the presence of plaque in the carotid arteries, possibly contributing to the worse prognosis observed in this group of patients.

Aged↗
PubMed1997

Phenotypic and cytokine analysis of human peripheral blood gamma delta T cells expressing NK cell receptors.

The presence of NK receptors (NKR) on populations of T cells has been proposed to play a regulatory role in T cell function, fine tuning the response to Ag, and influencing the nature of the immune response through rapid secretion of large amounts of cytokines. In this study, we assessed the nature and distribution of NKR on human peripheral blood gamma delta T cells and established clones to study cytokine release. In circulating gamma delta T cells, approximately 80% expressed CD94, approximately 25% expressed NKR-P1A, and approximately 20% expressed p58, values substantially higher than those found on alpha beta T cells from the same donors. When cloned for specific NKR expression, most cells in culture were NKR-P1A+ whereas p58 expression was variable, suggesting that the NKR-P1A phenotype can be acquired in culture whereas expression of p58 is more stable. Some clones were triple positive for CD94, NKR-P1A, and p58. V delta 2+ cells generally expressed a wider range of NKR than V delta 1+ cells. Following activation through CD3, all gamma delta T cell clones released large amounts of IFN-gamma, commencing as early as 4 h postactivation. Some clones also released TNF-alpha and IL-4, but no correlation with specific NKR expression was noted. Activation through NKR-P1A induced moderate levels of IFN-gamma without inducing IL-4. The results suggest that activation of most gamma delta T cells is regulated by signaling events occurring via both the TCR and the NKR. They further show that peripheral blood gamma delta T cells may function as a source of the proinflammatory cytokines IFN-gamma and TNF-alpha.

Cell Line↗
PubMed1997

Four-year follow-up of a case of acute multiple sclerosis of the Marburg type.

We describe the clinical course, treatment and magnetic resonance findings during a four-year follow-up of a patient with acute multiple sclerosis of the Marburg type, treated with steroid and mannitol therapy, who survived the first bout. Although the course of the disease was clinically indistinguishable from relapsing-remitting multiple sclerosis, our case was characterized by peculiar features. These included the need for protracted steroid therapy and the remarkable tendency of MRI lesions to resolve completely.

Adult↗
PubMed1997

HLA-DM polymorphisms do not associate with multiple sclerosis: an association study with analysis of myelin basic protein T cell specificity.

The MHC region on 6p harbors at least one susceptibility gene for multiple sclerosis (MS). Within this region, HLA-DM loci are of interest being involved in class II antigen processing. We investigated the association of HLA-DM polymorphisms with MS. Sixty-three patients with MS and 46 healthy controls from continental Italy were typed for HLA-DM polymorphisms and HLA-DRB1 alleles. Besides, among the donors characterized for the DM polymorphisms, we considered 6 MS patients previously studied for the fine specificity of their MBP-specific T lymphocyte lines (TLL). The frequencies of allelic variants at the DMA and DMB loci were similar between MS patients and controls, even when HLA-DRB1*1501 positive and negative donors were analyzed separately. Patients with predominant responses to different MBP epitopes did not differ for their HLA-DM haplotype while patients with predominant responses to the same MBP epitope could present different HLA-DM haplotypes. HLA-DM polymorphisms do not associate with MS and may not affect specific patterns of T cell responses to MBP.

Adult↗
PubMed1997

Down-regulation of cell-surface CD4 co-receptor expression and modulation of experimental allergic encephalomyelitis.

Pre-immunization with autoantigens confers resistance in experimental models of autoimmune diseases. Since non-self molecules can also be protective, it is conceivable that part of the effect rests on a non-specific attenuation of the immune response. This study is aimed at identifying mechanisms by which pre-immunization with a moiety suspended in incomplete Freund's adjuvant (IFA) protects from experimental allergic encephalomyelitis (EAE). Lewis rats were immunized with each of either concanavalin A, lipopolysaccharide, bovine serum albumin, 70 or 65 kDa heat shock proteins, or myelin basic protein. All moieties were given in IFA 3 weeks prior to EAE induction. Serial cytofluorimetric monitoring of B cells and of the alpha beta TCR+, CD4+, CD8+, CD45high and CD45low cells was performed. IFN-gamma and IgG1 production was evaluated in parallel. All moieties were able to attenuate or abrogate the clinical signs of EAE. At day 4 and 10 after EAE induction, the surface expression of the CD4 molecule was down-regulated on T lymphocytes. This down-regulation was most evident in animals with the highest degree of clinical protection. By day 21 post-immunization, CD4 expression was restored. The same animals also showed an increase in the B cell percentage and Th2-related IgG1 production while IFN-gamma secretion was reduced. Pre-immunization with diverse antigens suspended in IFA confers resistance to EAE induction. The down-regulation of the CD4 co-receptor accompanied by events suggestive of an immune deviation may be a general mechanism that contributes to the protection.

Animals↗
PubMed1997

Effects of long-term antihypertensive treatment with lisinopril on resistance arteries in hypertensive patients with left ventricular hypertrophy.

OBJECTIVE: To evaluate the effects of long-term antihypertensive therapy with the angiotensin converting enzyme inhibitor lisinopril on structural alterations and the endothelial function of small resistance arteries in hypertensive patients with left ventricular hypertrophy. METHODS: Fourteen patients with left ventricular hypertrophy were treated for 3 years with a lisinopril-based regimen. Patients underwent an echocardiographic evaluation of left ventricular mass index at baseline, during the first and third years of treatment. At the end of the treatment period, subcutaneous small resistance arteries (obtained by biopsy of the subcutaneous fat from the gluteal region) were dissected and mounted on a micromyograph (Mulvany's technique); the media : lumen ratio was then calculated. Data obtained were compared with those observed for 14 untreated essential hypertensive patients and 14 normotensive subjects, age- and sex-matched. RESULTS: In the present study, a significantly lower media : lumen ratio was observed in treated compared with untreated hypertensive patients, although it remained significantly higher than that in normotensive subjects. In treated hypertensive patients a significant reduction in clinic blood pressure was observed. However, their blood pressure remained significantly higher than that in normotensive subjects. Significant correlations between the media : lumen ratio and blood pressure, left ventricular mass index or changes in left ventricular mass index during treatment were observed. The response to acetylcholine administration was reduced in untreated hypertensives compared with that in normotensives. In patients treated with lisinopril, the vasodilatation obtained with the two higher doses of acetylcholine was greater than that in untreated hypertensives, thus suggesting an improvement of endothelial function. CONCLUSIONS: Long-term therapy based on lisinopril was associated with a smaller media : lumen ratio in the subcutaneous small resistance arteries of hypertensive patients with left ventricular hypertrophy. Our retrospective study confirms previous findings obtained in prospective studies with other angiotensin converting enzyme inhibitors. Endothelial function was probably improved by lisinopril therapy.

Aged↗
PubMed1997

Structural changes of small resistance arteries in spontaneously hypertensive rats after treatment with various doses of lacidipine.

OBJECTIVE: To evaluate the modifications of the morphology of mesenteric small resistance vessels in spontaneously hypertensive rats (SHR) induced by lacidipine treatment. METHODS: Lacidipine was administered at three different dosages, 20, 10, and 0.3 mg/kg per day. Fifty rats were studied. Nine SHR and 11 Wistar-Kyoto (WKY) rats were not treated. Each lacidipine dose was administered to 10 SHR. The drug and the placebo were administered by gavage from age 4 to age 12 weeks. The blood pressure was measured noninvasively every week. The animals were killed when they were aged 13 weeks, and the relative left ventricular mass (left ventricular weight plus septum weight/body weight) was calculated. Small mesenteric resistance vessels were dissected and mounted on a micromyograph (Mulvany's technique), and morphological parameters of the vessels were studied (media thickness and media: lumen ratio). RESULTS: The systolic blood pressure of SHR administered 20 and 10 mg/kg lacidipine per day was reduced significantly during the treatment period, whereas that of rats treated with 0.3 mg/kg lacidipine per day did not change. A significant reduction in media: lumen ratio was observed for all three groups of treated rats, including those to which 0.3 mg/kg lacidipine per day had been administered, and no reduction in systolic blood pressure could be detected. The relative left ventricular mass was reduced significantly only in rats to which 20 and 10 mg/kg lacidipine per day had been administered. CONCLUSION: A significant reduction in magnitude of vascular structural alternations was observed even in SHR treated with a low, nonhypotensive dose of lacidipine.

Animals↗
PubMed1997

LHON mutations in Italian patients affected by multiple sclerosis.

The occurrence of a multiple sclerosis (MS)-like phenotype in subjects carrying mitochondrial DNA (mtDNA) mutations associated with Leber hereditary optic neuropathy (LHON) has suggested that mitochondrial genes may contribute to susceptibility to MS. With the present study 74 unrelated Italian patients (53 females and 21 males; mean age 37.9, SD 9.9, range 20-59) affected by MS with early and prominent optic nerve involvement and 99 normal control subjects were analysed for the presence of primary (nps 11778, 3460, 14484) and an alleged secondary one (np 15257) LHON mutations. A single MS patient carrying a virtually homoplasmic LHON mutation at np 11778 was found. Family history revealed a maternal uncle affected by MS, decreased at age of 64 in consequence of a stroke. The patient's mother harboured the same mutation in a homoplasmic way. Primary LHON mutations were not detected in any other MS patient or control. Of the MS patients 5.4% (4 out of 74), and 5.1% (5 out of 99) of the controls carried the 15257 mutation in a homoplasmic state. Present data do not support any contribution of primary LHON mutations to genetically determined susceptibility in MS. There is no evidence that the 15257 mutation has any pathogenetic significance in the Italian population.

Adult↗
PubMed1997

No increase of serum autoantibodies during therapy with recombinant human interferon-beta1a in relapsing-remitting multiple sclerosis.

OBJECTIVES: The present investigation was aimed at establishing whether interferon (IFN)-beta would induce the synthesis of autoantibodies in patients affected by multiple sclerosis (MS). MATERIALS AND METHODS: The titres of different autoantibodies were measured in a group of 68 relapsing-remitting MS patients before and during treatment with human recombinant IFN-beta1a (3 MIU or 9 MIU subcutaneously 3x a week). ANA, anti-thyroid, anticardiolipin serum autoantibodies were assayed in all cases: when patients were found positive to ANA > 1 : 40, they were also tested for anti-DNA and anti-ENA antibodies. RESULTS: No increase was found in autoantibodies synthesis during 6 months of r-hIFNbeta1a therapy, either at low or high dosages. The percentage of patients positive to different types of autoantibodies varied between 0 and 29%, which are values similar to those already reported in untreated MS patients. CONCLUSION: Our data indicate that the short-term use of IFN-beta1a in MS is safe in terms of the induction of humoral autoimmune responses: however, further follow-up is needed to confirm these findings during long-term treatments.

Adjuvants, Immunologic↗
PubMed1997

[The absorbed dose to the gonads in adult patients undergoing defecographic study by digital or traditional radiographic imaging].

INTRODUCTION: Doses to the gonads and skin of adult people were evaluated during the study of functional anorectal disorders with defecography. MATERIALS AND METHODS: The radiologic procedure relies heavily on fluoroscopy with lateral and anteroposterior projections for a mean time of 2.4 minutes; the stages of interest are recorded on a mean of 6 films. Absorbed doses to the gonads and to the skin were measured with LiF thermoluminescence dosimeters placed inside and outside the anthropomorphic "Rando" phantom. The administered doses during the different examination phases (anteroposterior and lateral fluoroscopy and radiography) were measured. Digital and conventional radiography were compared. RESULTS: Gonadal absorbed doses in a standard DSI examination were: 5.0 +/- .1 mGy to the right ovary, 25.2 +/- .7 mGy to the left ovary and 2.7 +/- .1 mGy to testes when at the margin of the irradiation field. Doses to gonads and skin are about 15% higher when the examination is performed with conventional radiography. DISCUSSION: The considerable radiation dose to ovaries shows that defecography can cause radiation-induced genetic effects in women younger than 40 years with a probability of the order of one thousandth of the natural incidence genetic defects. CONCLUSIONS: Defecography must be correctly indicated in fertile women, because of the relatively high absorbed dose to ovaries. In fact, the ovaries absorb about twice as many radiations during defecography than radiologic examinations of the lower gastrointestinal tract.

Absorption↗