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Biomedical subjects

G Ferrari

Publications and source records attributed to G Ferrari.

At least 91 records · Page 5Linked to original sources
PubMed1999

Plasma levels of apolipoprotein E and genetic markers in elderly patients with Alzheimer's disease.

Besides apolipoprotein E (APOE) polymorphism, whose association with Alzheimer's disease (AD) has been confirmed in most of the numerous population samples studied, other markers have been investigated. In most cases the association firstly described was not confirmed in subsequent works. Since it is important to examine these associations in as many populations as possible, we investigated APOE, APOC1, APOC2, alpha-1 antichymotrypsin (ACT) and presenilin-1 (PS-1) polymorphisms in a series of elderly patients with late-onset sporadic AD from Northern Italy and in a sex and age-matched control group. We could not confirm the significantly higher frequency of the ACT*A allele among carriers of APOE e*4 allele described elsewhere, although a similar trend was observed. The APOC2 and the PS-1 distributions were similar between patients and controls. However, we observed a significant difference in the genotype and allele frequencies of APOE and APOC1: patients had higher e*4 and C1*2 allele frequencies. This finding confirms the important role for APOE in AD occurrence. In addition, APOC1 seems to be an interesting marker because, though in strict linkage disequilibrium with APOE, it seems to play an independent role in AD risk. In contrast to previously reported data, plasma apoE concentrations were similar in patients and in controls. An interaction between APOE and APOC1 polymorphisms and apoE levels was observed in patients: subjects carrying the APOE E3/E2 or the APOC1 2-2 genotype have higher apoE concentrations than those who do not.

Aged↗
PubMed1999

Evidence for an abnormal cortical sensory processing in dystonia: selective enhancement of lower limb P37-N50 somatosensory evoked potential.

We evaluated brain stem P30, contralateral frontal N37, and the vertex-ipsilateral central P37, N50 somatosensory evoked potentials (SEPs) obtained in response to stimulation of the tibial nerve in 10 patients with idiopathic dystonia. Results were compared with those obtained in 10 healthy subjects matched for age and sex. The amplitude of the brain stem P30 potential and of the contralateral frontal N37 response in dystonic patients was not significantly different from that recorded in normal subjects. The vertex- ipsilateral central P37-N50 complex, which is thought to originate in the pre-rolandic cortex, was significantly enhanced in patients compared with the control group. These results suggest the enhancement of the vertex-ipsilateral central P37-N50 complex might reflect an abnormal response to somatosensory inputs of a precentral cortex which is excessively activated because of a disorder of the basal ganglia. Such inefficient sensory processing in motor areas might contribute to motor impairment in dystonia.

Adult↗
PubMed1999

Bovine virus diarrhoea (BVD) control programme in an area in the Rome province (Italy).

A BVD control programme based on the identification and removal of persistently infected (PI) animals is being undertaken in an area in the Rome province, where BVD outbreaks had been previously detected. It involves 174 mainly dairy herds, from which blood samples of all bovines older than 1 year are obtained through the national brucellosis and leukosis eradication programme. Samples sufficient to detect the presence of seropositive animals at a prevalence of 5% or more are initially screened for antibodies against BVD virus (BVDV) using an immunoenzymatic assay. Upon identification of seroreagents additional blood samples are tested from the 6-12-month age category not included in the initial samples. Animals are considered immunotolerant if BVDV is demonstrated twice at a minimum 30-day interval. When no seropositive animals are detected during the first serological screening the herd is declared BVD-free if a second testing, preferably carried on the same animals previously tested, confirms the seronegative status of the herd. At present 147 farms have been tested, of which 63 (42.9%) are negative with respect to antibodies against BVDV. Of the 84 remaining herds in which one or more seropositives are detected, 13 are classified as recently infected. In eight of these recently infected herds, 22 PI animals have been identified.

Animals↗
PubMed1999

CD40 signaling induces B cell responsiveness to multiple members of the gamma chain-common cytokine family.

CD40 signaling induces B cell proliferative and differentiation responses that can be modulated by many different cytokines. Cytokines in the IL-2 receptor gamma chain (gammac)-common family are known to play an integral role in B cell development. Therefore, we investigated the possibility that CD40 signaling induced B cell responsiveness to multiple gammac-common cytokines and that individual gammac-common cytokines induced distinct B cell responses. B cells were isolated from lymphoid follicles of sheep Peyer's patches (PP) and co-cultured with murine CD40 ligand (mCD40L). CD40 signaling induced PP B cell responsiveness to recombinant human IL-2, IL-4, IL-7 and IL-15. mCD40L-induced B cell growth was enhanced by combining IL-4 with a second gammac-common cytokine and sustained B cell growth required co-stimulation with IL-4 plus IL-2, IL-7 and IL-15. gammac-common cytokine responsiveness remained dependent upon CD40 signaling, and removal of mCD40L resulted in B cell differentiation and cell death. Similar proliferative responses to mCD40L and gammac-common cytokines were observed for both immature (ileal) and mature (jejunal) PP B cells. Finally, the capacity of CD40-activated B cells to respond to multiple gammac-common cytokines was analyzed with individual PP B cell clones. All B cell clones displayed similar proliferative responses to IL-2 but quantitatively different responses to IL-4, IL-7 and IL-15. The biological significance of B cell responsiveness to multiple gammac-common cytokines is discussed.

Animals↗
PubMed1999

Energy depletion differently affects membrane transport and intracellular metabolism of riboflavin taken up by isolated rat enterocytes.

Isolated rat enterocytes, both normal and those de-energized with rotenone, were used to study the energy dependence of membrane and intracellular intestinal riboflavin transport in vitro. Membrane and intracellular transport were investigated by using short (3 min) and long (20 min) incubation times, respectively. For both types of cells and incubation times, [3H]-riboflavin uptake presented a saturable component prevailing at physiologic intraluminal concentrations. At 3 min incubation, saturable [3H]-riboflavin transport was apparently an energy-independent process with high affinity and low capacity. Values of the saturable component and its apparent constants, Km and Jmax, did not differ in normal and de-energized enterocytes. At 20 min incubation, saturable [3H]-riboflavin transport was a strictly energy-dependent process in which values of the saturable component were significantly greater in normal than in de-energized enterocytes. Km values did not differ in the two types of cells and were unmodified over 3 min, whereas in normal enterocytes, Jmax at 20 min [6.25 +/- 0.2 pmol/(mg protein. 20 min)] was significantly greater than at 3 min [2.67 +/- 0.33 pmol/(mg protein. 3 min)] and compared with de-energized enterocytes at 20 min [2.54 +/- 0.16 pmol/(mg protein. 20 min)]. Both membrane and intracellular events were inhibited by unlabeled riboflavin and analogs, which are good substrates for flavokinase, thus demonstrating the paramount role of this enzyme in riboflavin intestinal transport.

Animals↗
PubMed1999

Detection of human papillomavirus DNA in urinary bladder carcinoma by in situ hybridisation.

AIMS: To investigate the sensitivity of an in situ hybridisation system to detect human papillomavirus (HPV) infection in transitional cell bladder cancer and to evaluate the advantages of analysing multiple biopsies; to examine the correlation between HPV tumour infection detected by in situ hybridisation and the presence of serum anti-HPV antibodies detected by enzyme linked immunosorbent assay (ELISA); and to relate the presence of viral infection to grade, stage, and follow up in cases of bladder cancer. METHODS: The in situ hybridisation technique was used with broad spectrum and type specific (6/11, 16/18, 31/33/35) probes against HPV DNA in formalin fixed, paraffin embedded tissues from 43 cases of bladder cancer. The results were analysed for the presence and type of papillomavirus and correlated with clinicopathological variables. RESULTS: The presence of HPV DNA was identified by the in situ hybridisation technique in 17 of 43 cases of bladder cancer; 12 of these were serum antibody positive and 10 had had multiple biopsies. Fifteen of the cases that were negative for HPV DNA by in situ hybridisation had positive serum serology when tested by ELISA. In 14 cases, the HPV was either types 16/18 or types 31/33/35, both of which carry high oncogenic risk. The stage (p < 0.05) and grade (NS) of the tumour and the outcome on follow up (p < 0.05) were correlated with the presence of HPV infection. CONCLUSIONS: ELISA is not useful in identifying patients with HPV positive bladder cancer, but the use of several probes and multiple biopsies increases the detection rate of HPV in neoplastic tissues. The association between tumour virus infection and high grade/high stage tumours and worse outcome suggests that HPV infection of neoplastic tissue has a negative effect on the behaviour and evolution of transitional cell bladder carcinoma.

Adult↗
PubMed1999

Mental, physical and functional status in primary care attenders.

OBJECTIVE: The purpose of the present study was to analyze the association, in primary care attenders, between psychiatric disorders, medical comorbidity, and impairment in mental and physical function status. METHODS: The study had a two-stage design. The GHQ-12 was used to screen 1647 patients, and 323 of them were then interviewed using the CIDI-PHC to obtain ICD-10 diagnoses. Severity of mental illness was assessed using the Hamilton scales for anxiety and depression. The DUSOI was used to evaluate the severity of physical illness. The MOS SF-36 was used to assess health related quality of life. RESULTS: The estimated prevalence of ICD-10 psychiatric disorders and subthreshold disorders was 12.4 percent and 18 percent respectively. The most common psychiatric disorders were generalized anxiety, major depression, and neurasthenia. The severity of physical illness did not vary across diagnostic status categories. Significant impairment, both in physical and mental functioning was seen in patients suffering from ICD-10 full-fledged and subthreshold disorders. Severity of impairment increased from sub-threshold cases to full-fledged cases, and among the latter according to the severity of depressive and anxious symptoms, assessed using Hamilton scales. The most frequent psychiatric disorders were associated with significant worsening in health related quality of life, with relevant differences between psychiatric diagnoses regarding the domains affected. Impairment associated with mental disorders was greater than that associated with physical illness. CONCLUSIONS: The results of the present study confirm that ICD-10 psychiatric disorders are common in general practice and are associated with relevant impairment in physical and mental functional status. Psychiatric morbidity is not related to severity of physical illness rated by general practitioner.

Adult↗
PubMed1999

[Primary angioplasty in acute myocardial infarct with or without a stent implant: the experience and results at 6 months in the first 200 patients].

BACKGROUND: Although it is superior to thrombolysis, primary PTCA does have some limitations, both in hospital (recurrent ischemia and reinfarction due to reocclusion of the infarct-related artery) and at the six-month follow-up (high rate of late restenosis). Coronary stenting is a promising way of solving some of these problems, even if its use in patients with acute myocardial infarction could prove to be controversial because of intracoronary thrombus. In this study, we propose two procedural strategies in the treatment of the infarct-related artery (IRA): the search for optimal angiographic results after PTCA ("stent-like result"--SLR--with residual stenosis < or = 20%--no dissection--TIMI III flow) or intracoronary stenting when SLR was not obtained after a second inflation. METHODS AND RESULTS: From December 1995 to May 1998, 200 patients with AMI underwent direct PTCA or rescue PTCA because of failed thrombolysis. There were 143 men and 57 women, mean age 65 (range 36-84). Nineteen patients were in cardiogenic shock and 25 were in Killip class > II. Recanalization of the IRA was achieved in 196 patients (98%). In four patients, it was not possible to cross total occlusion with the guide-wire. SLR post-PTCA was achieved in 40 patients (20%). Stents were placed in 147 patients (75%), with "elective" implantation in 73 lesions because of suboptimal results after PTCA in 41, and early loss or coronary dissection with threatening occlusion in 33. In nine patients without SLR, stenting was not performed because of diffuse disease of the IRA. In-hospital complications included ten deaths (8 of 19 patients with cardiogenic shock at admission and 2 with multivessel disease and severe left ventricular dysfunction). None of the patients required emergency coronary bypass for procedural complications. One patient had a subacute thrombosis on the third day after bail-out stent implantation (re-PTCA). Five patients required elective bypass surgery to complete revascularization for multivessel disease with ten days after the surgical procedure. At the six-month follow-up, one patient had died of cardiogenic shock. Eleven (5%) patients with bail-out procedures underwent coronary bypass surgery or PTCA. Thirty-one patients (31/168) had recurrence of ischemia: 15 patients in the stent group, 11 in SLR group and 5 in the non-SLR group. Re-PTCA was performed in 20 patients, CABG in five and medical therapy in six. Other patients were angina-free at follow-up. CONCLUSIONS: Based on our experience, seeking optimal angiographic results with or without (SLR) stent implantation is a safe and effective operative approach to achieve the best procedural and clinical outcome and reduce complications in patients undergoing PTCA for AMI.

Aged↗
PubMed1999

The influence of simultaneous intra-aortic balloon pumping and mechanical ventilation on hemodynamic parameters--numerical simulation.

Intra-aortic balloon counterpulsation (IABC) is one of the methods to assist circulation. Its application is supposed to increase coronary blood flow (Qcor) and myocardial oxygen supply. Mechanical ventilation of the lungs causes some side effects that influence mainly hemodynamics, i.e. it decreases cardiac output (CO) and systemic aortic pressure (Pas) but increases systemic venous pressure (Pvs). The aim of this study was to assess the influence of IABC on hemodynamic parameters when mechanical ventilation of the lungs is used as well. We assumed pathological conditions of the heart as reduced left ventricle elastance (Ev = 0.77 mmHg/cm3) and increased left ventricle rest volume (V0 = 10 cm3). Also peripheral systemic arterial resistance (Ras) took three different values. CARDIOSIM, a computer simulator of the human cardiovascular system, was used to assess the changes of hemodynamic parameters [CO, Pas, Pvs, and pulmonary arterial pressure (Pap)] when IABC and mechanical ventilation of the lungs were applied simultaneously. Computer simulation showed that application of IABC increased such variables as CO (by approximately equal to 17%), maximum value of Pas (by approximately equal to 20%), while left atrial pressure (Pla) was diminished (by approximately equal to 30%). On the other hand, Pvs and Pap were not strongly affected by IABC, but they were dramatically dependent on intrathoracic pressure. This means that Pvs, Pap, and Pla should be carefully monitored during IABC and artificial ventilation.

Blood Pressure↗
PubMed1999

Percutaneous transmyocardial revascularization with holmium laser in patients with refractory angina: a pilot feasibility study.

BACKGROUND: Percutaneous transluminal myocardial revascularization (PTMR) is a new procedure to improve perfusion of the ventricular wall for patients with intractable angina that is untreatable by surgery or conventional catheter-based intervention. PTMR allows the creation of myocardial channels through the controlled delivery of holmium laser energy from the ventricular chamber. Preliminary studies in animals and human subject have yielded promising results. We now report the feasibility study of PTMR using a laser delivered through a novel Eclipse system, and we present the results of this sole therapy in patients with severe coronary disease and angina refractory to maximal medical treatment angina (III-IV CCS). METHODS: Percutaneous vascular access for PTMR treatment was obtained via the femoral artery. A 9F directional catheter carrying flexible fiber optics was used with a holmium laser (Eclipse system) and was placed across the aortic valve into the left ventricle cavity to create channels with a depth of 5 mm from the endocardial surface into the myocardial tissue. From April to November 1998, 15 patients underwent PTMR with Eclipse system. Two patients were female; the mean age was 66 +/- 8 (range 59-74). Five patients had a severe LV dysfunction (FE < 30%). Preoperative angina class was III in 10 patients and IV in 5 and previous myocardial procedures had been performed in all patients. RESULTS: The procedure was well tolerated and procedural success was obtained in 14 of 15 patients. There was one myocardial perforation because of guiding-catheter manipulation (pericardial drainage in fourth day). We performed a mean of 13 +/- 4 channels in a mean fluoro time of 23 +/- 11 min. Upon release and during follow-up (5.3 months +/- 4.2, range 2-10), angina class had significantly improved in 14 of 14 patients with complete PTMR treatment, with 4 asymptomatic patients, 6 patients in CCS I, 3 in CCS II, 2 in CCS III and only one patient hospitalized due to angina. CONCLUSION: This pilot study confirmed the safety and technical feasibility of PTMR. Immediate and short-term results confirm that a clinical improvement is obtained in most patients. Although these are early clinical benefits, the true efficacy of this approach will necessarily be defined by a randomized trials with prospectively-defined endpoints and with PTMR compared with medical therapy.

Aged↗
PubMed1998

Promotion of neuronal survival by GM1 ganglioside. Phenomenology and mechanism of action.

The purpose of this article is to review recent findings regarding the mechanisms by which GM1 may mimic or potentiate certain actions of neurotrophic factors, including promotion of neuronal survival. It is proposed that the neuroprotective activity of GM1 is due, at least in part, to its ability to favor the dimerization of neurotrophic factor tyrosine kinases and thereby mimicking the action of their corresponding ligands. This may manifest both in the absence of ligand (thereby triggering a subset of neurotrophic-factor responses such as prevention of apoptosis) and in the presence of ligand (thereby potentiating responses to neurotrophic factors).

Animals↗
PubMed1998

High efficiency myogenic conversion of human fibroblasts by adenoviral vector-mediated MyoD gene transfer. An alternative strategy for ex vivo gene therapy of primary myopathies.

Ex vivo gene therapy of primary myopathies, based on autologous transplantation of genetically modified myogenic cells, is seriously limited by the number of primary myogenic cells that can be isolated, expanded, transduced, and reimplanted into the patient's muscles. We explored the possibility of using the MyoD gene to induce myogenic conversion of nonmuscle, primary cells in a quantitatively relevant fashion. Primary human and murine fibroblasts from skin, muscle, or bone marrow were infected by an E1-deleted adenoviral vector carrying a retroviral long terminal repeat-promoted MyoD cDNA. Expression of MyoD caused irreversible withdrawal from the cell cycle and myogenic differentiation in the majority (from 60 to 90%) of cultured fibroblasts, as defined by activation of muscle-specific genes, fusion into contractile myotubes, and appearance of ultrastructurally normal sarcomagenesis in culture. 24 h after adenoviral exposure, MyoD-converted cultures were injected into regenerating muscle of immunodeficient (severe combined immunodeficiency/beige) mice, where they gave rise to beta-galactosidase positive, centrally nucleated fibers expressing human myosin heavy chains. Fibers originating from converted fibroblasts were indistinguishable from those obtained by injection of control cultures of lacZ-transduced satellite cells. MyoD-converted murine fibroblasts participated to muscle regeneration also in immunocompetent, syngeneic mice. Although antibodies from these mice bound to adenoviral infected cells in vitro, no inflammatory infiltrate was present in the graft site throughout the 3-wk study period. These data support the feasibility of an alternative approach to gene therapy of primary myopathies, based on implantation of large numbers of genetically modified primary fibroblasts massively converted to myogenesis by adenoviral delivery of MyoD ex vivo.

Adenoviridae↗
PubMed1998

Muscle regeneration by bone marrow-derived myogenic progenitors.

Growth and repair of skeletal muscle are normally mediated by the satellite cells that surround muscle fibers. In regenerating muscle, however, the number of myogenic precursors exceeds that of resident satellite cells, implying migration or recruitment of undifferentiated progenitors from other sources. Transplantation of genetically marked bone marrow into immunodeficient mice revealed that marrow-derived cells migrate into areas of induced muscle degeneration, undergo myogenic differentiation, and participate in the regeneration of the damaged fibers. Genetically modified, marrow-derived myogenic progenitors could potentially be used to target therapeutic genes to muscle tissue, providing an alternative strategy for treatment of muscular dystrophies.

Animals↗
PubMed1998

Dystonia in a patient with deletion of 18p.

18p- syndrome from chromosomal deletion of the short arm of chromosome 18 shows a wide range of clinical manifestations. Mental retardation is the most frequent neurological complication; other neurological deficits are more rarely reported. Only one 18p- patient with focal dystonia at the lower limbs has been reported, while there have been no reported cases of generalized dystonia. We report a 27-year-old male with 18p- de novo complete deletion (karyotype 46,XY,18p-) who was affected by severe generalized dystonia, hypokinesia, mental retardation and dysmorphic features. The 18p- syndrome should be added to the list of genetic causes of secondary dystonia. A karyotype analysis should be considered in secondary dystonias, particularly when there are associated dysmorphic features and mental retardation.

Adult↗
PubMed1998

The influence of left ventricle assist device and ventilatory support on energy-related cardiovascular variables.

One of the main purposes in using Left Ventricle Assist Devices (LVAD) to assist recovery in patients with heart failure, is to reduce the external work (EW) of the left natural ventricle. The simultaneous presence of mechanical ventilatory support can affect the value of this variable. The aim of our computer simulation was to trace the influence of LVAD on EW, cardiac mechanical efficiency (CME) and pressure volume area (PVA) in the presence of ventilatory support. Pathological conditions of the heart were reproduced. Peripheral systemic arterial resistance (Ras) was also changed to model physiological and pathological states. The influence of mechanical ventilation was introduced by changing levels of mean thoracic pressure. In this way we were able to predict changes of EW, CME and PVA in both ventricles, during ventilatory (mechanical) and cardiovascular (LVAD) support. Our simulation showed that positive thoracic pressure seems to affect the energy-related cardiovascular variables and should be taken into account during the assessment of LVAD effectiveness. Pathological changes of systemic peripheral resistance have a considerable effect on EW, CME and PVA of left ventricle. On the other hand energy-related parameters of the right ventricle are not especially affected by changes in systemic peripheral resistance.

Computer Simulation↗