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Biomedical subjects

M Vaccari

Publications and source records attributed to M Vaccari.

At least 19 recordsLinked to original sources

Einstein and Debye models for EXAFS parallel and perpendicular mean-square relative displacements.

The correlated Einstein and Debye models for EXAFS parallel mean-square relative displacement (MSRD) are derived from the general expression in terms of eigenfrequencies and eigenvectors of the dynamical matrix, without ad hoc assumptions. The two models are generalized to parameterize also the EXAFS perpendicular MSRD. The physical meaning of Einstein frequencies, as well as the application of the Debye model to crystals with more than one atom per cell, are critically discussed.

Algorithms↗

Risk factors for type 2 diabetes in women attending menopause clinics in Italy: a cross-sectional study.

OBJECTIVE: To analyze risk factors for type 2 diabetes among women attending menopause clinics in Italy for counselling about the menopause. SUBJECTS: Women attending a network of first-level outpatient menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms. METHODS: Cross-sectional study with no exclusion criteria. Type 2 diabetes was defined according to National Diabetes Data Groups Indications and the fasting blood glucose at an oral glucose tolerance test within the previous year. RESULTS: Out of the 44 694 considered in this analysis, 808 had a diagnosis of diabetes type 2 (1.8%). In comparison with women aged < 50 years, the multivariate odds ratios (OR) of type 2 diabetes were 1.31 (95% confidence interval (CI), 0.99-1.74) for women aged 50-52 years, 1.66 (95% CI, 1.27-2.17) at 53-56 years and 2.84 (95% CI, 2.20-3.67) in women aged > or = 57 years. Type 2 diabetes was less frequently reported in more educated women (OR high school/university vs. primary school = 0.44 (95% CI, 0.36-0.55)). Being overweight was associated with an increased risk of type 2 diabetes. In comparison with women reporting a low level of physical activity, the multivariate OR of type 2 diabetes was 0.67 (95% CI, 0.54-0.84) for women reporting regular physical activity. In comparison with premenopausal women, the multivariate OR of type 2 diabetes was 1.38 (95% CI, 1.03-1.84) in women with natural menopause. This finding was present also after allowing for the potential confounding effect of age. The multivariate OR of diabetes for users of hormonal replacement therapy was 0.58 (95% CI, 0.46-0.73). CONCLUSIONS: This large cross-sectional study suggests that postmenopausal women are at higher risk of type 2 diabetes after allowance for the effect of age. Other main determinants of risk of type 2 diabetes in women around menopause were low socioeconomic status and being overweight. Diabetes was found less frequently in those taking hormone replacement therapy.

Age Distribution↗

The exstrophy-epispadias complex: is aesthetic appearance important?

OBJECTIVE: To show the relevance of cosmetic appearance in the adequate treatment of patients with exstrophy-epispadias complex (EEC), and to indicate that surgery by experienced teams can improve the long-term treatment forecast and the patient's body image. PATIENTS AND METHODS: From 1978 to 2002, 71 patients diagnosed with EEC were treated in the authors' institution; 24 (aged 2-23 years) were selected to undergo different surgical procedures. The criterion for surgery considered interviews conducted by the psychology team with the parents and children. The plastic surgery and paediatric urology teams carried out the procedures jointly; the follow-up was 0.33-7 years. RESULTS: Five female patients and six male had abdominoplasty to treat multiple scars; eight had intermittent catheterization conduits repositioned from the right iliac fossa to the umbilicus. Six female patients had plastic surgery of the external genitalia and three had a broad mobilization of the urogenital sinus. Thirteen male patients had a small penis and had the corpora cavernosa fully mobilized and the penis reconstructed. Five female patients and one male had anterior osteotomy. One patient with no left testis had it replaced and one patient with uterine prolapse had the uterus fixed to the posterior abdominal wall. Six patients had a second procedure, in two because the outcome of the initial operation was poor and in the others to complement the initial treatment. In all but one patient there was an improvement in the objective criteria, e.g. school absences, difficulty in establishing long-lasting social relationships and refusal to participate in sports activities. However, none of the patients would attempt sexual intercourse. CONCLUSIONS: Body image, self-esteem, sexuality, sexual function and fertility are deemed crucial by adolescents; in patients with EEC customised surgical procedures can give a satisfactory aesthetic outcome, and be a further reason for adequately following occasional urinary complications and renal function, to avoid loss to follow-up.

Adolescent↗

Altered maturation of peripheral blood dendritic cells in patients with breast cancer.

Tumours have at least two mechanisms that can alter dendritic cell (DC) maturation and function. The first affects the ability of haematopoietic progenitors to differentiate into functional DCs; the second affects their differentiation from CD14+ monocytes, promoting an early but dysfunctional maturation. The aim of this study was to evaluate the in vivo relevance of these pathways in breast cancer patients. For this purpose, 53 patients with invasive breast cancer were compared to 68 healthy controls. To avoid isolation or culture procedures for enrichment of DCs, analyses were directly performed by flow cytometry on whole-blood samples. The expression of surface antigens and intracellular accumulation of regulatory cytokines upon LPS stimulation were evaluated. The number of DCs, and in particular of the myeloid subpopulation, was markedly reduced in cancer patients (P<0.001). Patient DCs were characterized by a more mature phenotype compared with controls (P=0.016), and had impaired production of IL-12 (P<0.001). These alterations were reverted by surgical resection of the tumour. To investigate the possible role of some tumour-related immunoactive soluble factors, we measured the plasmatic levels of vascular endothelial growth factor, IL-10 and spermine. A significant inverse correlation between spermine concentration and the percentage of DCs expressing IL-12 was found. Evidence was also obtained that in vitro exposure of monocyte-derived DCs to spermine promoted their activation and maturation, and impaired their function. Taken together, our results suggest that both the above-described mechanisms could concomitantly act in breast cancer to affect DC differentiation, and that spermine could be a mediator of dysfunctional maturation of DCs.

Adult↗

Left ventricular remodelling, and systolic and diastolic function in young adults with beta thalassaemia major: a Doppler echocardiographic assessment and correlation with haematological data.

OBJECTIVE: To evaluate left ventricular morphology and function in a large population of patients with beta thalassaemia. DESIGN: Echo Doppler assessment of left ventricular function and correlation of cardiovascular data with haematological data. SETTING: Thalassaemia unit in a tertiary referral centre. PATIENTS: 197 young adults with beta thalassaemia, following an adequate transfusional and chelation treatment regimen, without clinical signs of cardiopulmonary involvement. The control group consisted of 213 healthy subjects. RESULTS: Left ventricular volumes, mass index, and mass/volume ratio were increased. Diastolic and systolic shapes were different, the left ventricle maintaining an ellipsoidal shape. The ejection fraction was reduced, and was < 50% in 33 patients. Stroke volume and cardiac index were increased, and systemic vascular resistance was decreased. Fractional shortening and mean velocity of circumferential shortening were decreased. Meridional end systolic and peak systolic stress were increased, as was circumferential end systolic stress. The contractile state was reduced while the functional preload index did not differ. Left ventricular diastolic function, evaluated from the mitral inflow, showed a slightly prolonged isovolumic relaxation time, increased flow velocity integrals, and an increased E/A ratio. Among the haematological data, only serum ferritin showed a weak negative correlation with left ventricular ejection fraction. The patients with the highest serum ferritin (> 2500 ng/ml) had the lowest ejection fraction. CONCLUSIONS: Patients with beta thalassaemia on an adequate transfusion and chelation treatment regimen show abnormal left ventricular remodelling with increased volumes, mass, and mass/volume ratio. Systolic chamber function and contractile state are reduced, with a slightly increased afterload. These findings seem mainly to be related to the increased cardiac output caused by chronic anaemia. Left ventricular performance is better preserved when chelation treatment is adjusted to maintain the serum ferritin concentration at < 1000 ng/ml.

Adolescent↗

[Cytofluorimetric evaluation of peripheral blood dendritic cells in patients with Mediterranean Kaposi's sarcoma].

AIM: Kaposi's sarcoma (KS) is a lympho-angioproliferative disorder characterized by angiomatous nodules and plaques that mainly affect the skin. The disease is consistently associated with human herpesvirus-8 (HHV8) and with a state of preexistent immunosuppression. Dendritic cells (DCs) have an instrumental role in the activation and function of both innate and adaptative immune responses. At least 2 distinct subsets have been characterized in peripheral blood based on phenotypic markers: myeloid DCs (CD11c+), associated with Ag uptake, T cell activation and ability to secrete IL-12, and plasmacytoid DCs, high virus-induced IFN-alpha producing cells. Because of the role of both DC subtypes in antiviral and antitumor induced responses, we hypothesized that DCs could be involved in the onset and evolution of KS. METHODS: Thirty-five patients with mediterranean KS assigned to different clinical stages were compared with 51 healthy control subjects. Peripheral blood DCs were quantified and functionally characterised by flow cytometry directly on whole blood samples. The production of the regulatory cytokines, IL-12 and IL-10, was assessed as intracellular accumulation after incubation with or without lipopolysaccharide (LPS). RESULTS: Myeloid DCs identified as lineage-/HLA-DR+/CD11c+ cells were significantly lower in KS patients than in controls (0.54+/-0.25 vs 0.69 +/-0.26% of the peripheral blood mononuclear cells; p<0.017). Furthermore, CD11c+ DCs were lower in patients with more diffuse disease. Plasmacytoid DCs, identified as lineage-/HLA-DR+/CD123+ cells, were lower in KS patients (0.23+/-0.19 vs 0.36+/-0.17; p<0.001). DCs from KS patients were more mature, as assessed by expression of the maturation marker CD83, and showed an impaired ability to produce IL-12 upon LPS stimulation, as compared with controls. CONCLUSION: The numerical and functional alterations of peripheral blood DCs observed in KS patients suggest an involvement of these cells in the onset and evolution of the disease.

Aged↗

S-100 protein and neuron-specific enolase as markers of subclinical cerebral damage after cardiac surgery: preliminary observation of a 6-month follow-up study.

Cerebral damage remains one of the hazards related to cardiac surgery with cardiopulmonary bypass. The use of biochemical markers of cerebral injury may be of practical value. We investigated the plasma release patterns of S-100 protein and neuron-specific enolase (NSE) during the intervention and their relationship with the development of neuropsychological deficits assessed 6 months after the intervention in 16 patients undergoing elective cardiac surgery with cardiopulmonary bypass. Both S-100 and NSE significantly increased peri- and postoperatively. Significant correlations were found between values measured at several time points and impaired performance in a few tests at the 6-month follow-up. A stratification into two age subgroups led to the hypothesis that age might have a confounding or a modifying effect on the association between S-100 and NSE levels, and cognitive impairment.

Aged↗

Reversal of malignant phenotype in human osteosarcoma cells transduced with the alkaline phosphatase gene.

Alkaline phosphatases are a family of glycoproteins that are able to hydrolize various monophosphate esters at a high pH optimum. Liver/bone/kidney (L/B/K) alkaline phosphatase (ALP) is one of the four major isoenzymes that belong to this family. Apart from its role in normal bone mineralization, other functions of L/B/K ALP remain obscure, both in physiological and in neoplastic conditions, including the bone-forming tumor osteosarcoma. In this study, we transfected the U-2 OS osteosarcoma cell line, which does not show any basal expression of this enzyme, with the full-length gene of L/B/K ALP, and analyzed the in vitro and in vivo features of four transfectants showing different expression of L/B/K ALP. A reduced in vitro ability to invade Matrigel and to grow in a semi-solid medium, together with a lower tumorigenic and metastatic ability in athymic mice, was found to be associated with a high level of cell surface L/B/K ALP activity. Moreover, L/B/K ALP transfectants showed a reduced secretion of matrix metalloproteinase-9 enzyme. These findings indicate a loss of aggressiveness of osteosarcoma cells after the expression of L/B/K ALP on their surface and suggest a new role for this enzyme.

Alkaline Phosphatase↗

Cardiac troponin I and Q-wave perioperative myocardial infarction after coronary artery bypass surgery.

OBJECTIVE: To monitor cardiac troponin I (cTnI), a newly developed biochemical index for cardiac damage, in patients during and after coronary artery bypass surgery (CABS) to determine whether the measurement of the serum levels of this marker could be of value in formulating an early diagnosis of Q-wave perioperative myocardial infarction (PMI). DESIGN: Prospective study with sequential measurements of biological markers in a selected surgical patient group. SETTING: University research laboratory and general university hospital (Cardiac Surgery Unit and Anesthesiology and Reanimation Unit). PATIENTS: Forty-two patients undergoing elective CABS without concomitant valvular replacement. INTERVENTIONS: There were no interventions required for this study. However, patients entered into the study had CABS, sequential arterial blood samples, ECG recordings, and echocardiograms performed. MEASUREMENTS AND MAIN RESULTS: Pre-, intra-, and postoperative (up to 48 hrs) measurements of cardiac troponin I, MB-CK, and total creatine kinase, as well as serial electrocardiograms and echocardiograms. Perioperative infarction was assessed as the development of new persistent regional wall motion abnormalities in echocardiography together with electrocardiographic alterations and MB-CK increases. Eight patients had Q-wave PMI. All PMI patients had elevated peak cTnI values (all >9.2 ng/mL), whereas the 34 nonPMI patients had peak values <9.0 ng/mL; therefore, sensitivity and specificity (with a 9.0 ng/mL cut-off value) are 100%. MB-CK measurement peak values did not demonstrate such a high specificity and sensitivity. CONCLUSIONS: Because of its high specificity and sensitivity, serial measurements of cTnI provide a rapid and accurate method for confirming or excluding the diagnosis of perioperative myocardial injury. cTnI evaluation can therefore be used both as an independent prognostic marker for patients undergoing cardiac surgery and as a powerful tool for detecting smaller PMIs often missed with standard PMI diagnostic criteria.

Aged↗

A major involvement of the cardiovascular system in patients affected by Marfan syndrome: novel mutations in fibrillin 1 gene.

The aim of our study was to characterize the molecular defect in Italian Marfan patients, thus contributing to the effort of correlating the genotype with the phenotype. In particular, our ultimate goal was to identify the region(s) of the fibrillin 1 (FBN1) gene mainly involved in the health of the heart and of the aorta in terms of the cardiovascular system. We searched for a molecular defect in three patients with classic Marfan syndrome (MFS). The mutations were detected applying heteroduplex analysis to each of the 65 exons of the FBN1 gene amplified by polymerase chain reaction (PCR). Exons containing heteroduplex bands were sequenced directly from PCR products. This study reports the detection of three unique missense mutations in the FBN1 gene in three Italian patients: a 44-year-old adult male and 36-year-old female affected by classic MFS (with all the cardinal manifestations in the cardiovascular, ocular and skeletal systems), and an 11-year-old male affected by infantile (earlier onset) classic MFS. The first two are sporadic cases and present a Cys-->Arg amino acid substitution (T-->C substitution at nucleotide 7729) in exon 62 and a Cys-->Tyr amino acid substitution (G-->A substitution at nucleotide 6695) in exon 54. The third is a familial case which presents a Cys-->Trp aminoacidic substitution (C-->G substitution at nucleotide 3546) in exon 28. Our data confirm that cysteine substitutions in calcium binding epidermal growth factor (cbEGF)-like domains cause severe Marfan phenotype. Exon 24-32 cluster seems to produce an even more severe phenotype. The early characterization may be of clinical relevance for prevention and early surgical treatment of aortic aneurysm or dissection.

Adult↗

Multidrug resistance and malignancy in human osteosarcoma.

In osteosarcoma, resistance to chemotherapy and metastatic spread are the most important mechanisms responsible for the failure of current multimodal therapeutic programs. We have shown previously that overexpression of the MDR1 gene product P-glycoprotein is the most important predictor of an adverse clinical course in patients with osteosarcoma. treated with chemotherapy. In this study, we analyzed the relationship between P-glycoprotein expression and local aggressiveness and systemic dissemination of multidrug-resistant (MDR) human osteosarcoma cells. Compared to parental sensitive cells, MDR cells showed a decreased tumorigenicity,and metastatic ability in athymic mice, together with a reduced migratory and invasive ability and a lower homotypic adhesion ability in vitro, suggesting that P-glycoprotein overexpression is associated with a less malignant phenotype. These experimental observations were confirmed by clinical data. In fact, the time of appearance of lung metastases in a series of osteosarcoma patients treated with chemotherapy was significantly shorter in the group of cases with no expression of P-glycoprotein in the primary lesion compared to the group with P-glycoprotein overexpression. Moreover, the incidence of P-glycoprotein overexpression was found to be higher among patients with localized disease at the clinical onset than in patients with evidence of metastasis at the time of diagnosis. These data indicate that, in osteosarcoma, the MDR phenotype is not associated with a more aggressive behavior both in vitro and in clinical settings, suggesting that the previously shown association of the MDR phenotype with a worse outcome in osteosarcoma is not related to a higher metastatic ability of cells with P-glycoprotein overexpression but is more likely due to their lack of responsiveness to cytotoxic drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Potentiating effect of galanin on GHRH-induced GH release. Comparison between old and young subjects.

The aim of our study was to investigate the effect of galanin on basal and GHRH-stimulated GH secretion in a healthy group of elderly subjects and in a healthy group of young subjects for comparison. Ten old subjects (mean age 75 +/- 1.15 years) and an equal number of healthy young volunteers (mean age 26 +/- 0.71 years) underwent three stimulation tests in random order. Galanin infusion for 60 minutes (10 micrograms/kg in 100 ml saline) failed to provoke an appreciable release of circulating GH in old subjects, while it induced a significant increase of plasma GH in the young adults; GHRH administration i.v. in bolus (100 micrograms in 1 ml saline) elicited a significant GH response in both groups; however, in the older group GH response was significantly (p < 0.05) lower than in the young adults. The administration of galanin (10 micrograms/kg in 100 ml saline as an i.v. infusion for 60 min) plus GHRH (100 micrograms in 1 ml saline i.v. in bolus), potentiated GH response in old and young subjects. The combined administration of two peptides was able to elicit a clear GH release even in the older subjects who were hyporesponsive/unresponsive to galanin and/or GHRH alone. In the elderly, plasma GH values observed after the combined stimuli overlapped with GH values observed after GHRH alone in the young adults. In conclusion, our study confirms that galanin has a synergic effect with GHRH on GH release both in younger and elderly subjects. Moreover, our data confirm an impaired responsivity to GHRH in the elderly and demonstrate that galanin is able to normalize response of somatotrophs to GHRH in old people.

Adult↗

Enhancement of BALB/c 3T3 cells transformation by 1,2-dibromoethane promoting effect.

Two of the most representative halogenated aliphatic hydrocarbons, 1,2-dibromoethane and 1,1,2,2-tetrachloroethane, were tested in the two-stage cell transformation model for analysing the promoting ability. Both of these compounds had previously been found to exert genotoxic effects, probably acting as moderate initiators. BALB/c 3T3 cells were initiated with subtransforming doses of N-methyl-N-nitro-N-nitrosoguanidine or 3-methylcholanthrene and then exposed to a chronic treatment with different non-transforming dosages of the two haloalkanes. 1,1,2,2-Tetrachloroethane did not exert any promoting activity in that system. By contrast, significant promoting effects by 1,2-dibromoethane were observed both in cells treated with N-methyl-N-nitro-N-nitrosoguanidine and in cells treated with 3-methylcholanthrene. Promotion of the transformation process initiated with 3-methylcholanthrene was detectable when confluent cells in the chemical-treated plates were replated in the level-II amplification test. This experimental procedure allowed cells to perform further rounds of replications and transformed foci to became detectable. Results gave evidence for a promoting role of 1,2-dibromoethane in multistep carcinogenesis, probably responsible for the higher oncogenic ability of this compound with respect to 1,1,2,2-tetrachloroethane.

3T3 Cells↗

1,2-Dibromoethane as an initiating agent for cell transformation.

The two-stage transformation assay increases the sensitivity of cells to chemicals and permits detection of carcinogens acting as initiating agents. 1,2-Dibromoethane, a representative halogenated aliphatic, has been tested in the two-stage BALB/c 3T3 cells transformation test at dosage from 16 microM to 128 microM. This dose range is much lower than those previously found efficient in transforming BALB/c 3T3 cells. Apart from the lowest dose, which induced borderline effects, all the other assayed dosages appeared to induce heritable changes in the target cells. The initiated cells were revealed as fully transformed foci both in the combination with a chronic promoting treatment and also by allowing cells to perform more rounds of cell replication. The results clearly show that 1,2-dibromoethane can act as an initiator of cell transformation.

3T3 Cells↗

The response of the ageing heart to regular physical exercise. An echo and Doppler study.

In upper middle age healthy subjects the functional cardiac reserve is known to be decreased (Port et al., 1980; Aubert et al., 1994). On the other hand regular physical exercise improves the cardiovascular function (Nishimura et al., 1980). The aim of this study was to establish whether regular physical exercise is associated with a significant change in the ageing process of the cardiovascular system.

Aging↗

An estimation of the left ventricular diastolic function from the spectral analysis of the fourth heart sound. A Doppler validated study in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a typical primary cardiac disease characterized by diastolic abnormal function due to both prolonged relaxation and decreased compliance (Sanderson et al., 1977; Spirito & Maron, 1990). Since the contribution of the atrial systole to ventricular filling is usually increased, the appearance of a fourth heart sound (S4) is a common finding in HCM. This sound is related to the ventricular compliance and to the atrial contractility. It is generated during the rapid setting into vibration of the left ventricular walls that results from the rapid rush of the blood due to the atrial contraction (Nishimura et al., 1989; Tavel, 1978). The aim of this study is to look for relationships between the frequency peak of S4 and various mono- and two-dimensional echocardiographic parameters in order to identify those cardiac structures involved in its genesis and obtaining an estimation of the stiffness of the acoustic vibrating system with a simply vibratory model (Baracca et al., 1991).

Cardiomyopathy, Hypertrophic↗