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Biomedical subjects

F Serino

Publications and source records attributed to F Serino.

At least 19 recordsLinked to original sources

Validity and reliability of an Italian version of the revised Leeds disability questionnaire for patients with ankylosing spondylitis.

OBJECTIVE: The purpose of the present study was to produce an Italian version of the Revised Leeds Disability Questionnaire (LDQ) in a group of patients with ankylosing spondylitis, and to examine the psychometric properties of this version, evaluating its internal consistency, external validity and reliability. METHODS: The LDQ was administered to 60 Caucasian patients affected by ankylosing spondylitis (50 males, 10 females, mean age 46.1 +/- 14.2 yr, range 22-74, median disease duration 4.5 yr, range 1-24) together with the Italian version of the Stanford Health Assessment Questionnaire (HAQ), and anthropometric measurements. Thirty patients completed the questionnaire after a 10-day interval. Internal consistency was evaluated with Cronbach's alpha coefficient of reliability. Construct validity of the LDQ was evaluated using the correlation between the HAQ and anthropometric measurements. Test-retest reliability was assessed with the intraclass correlation coefficient. RESULTS: All patients completed the validation study. The questionnaire was internally consistent (alpha=0.90). A significant correlation was recorded between the LDQ and the HAQ score (rho=0.841, P<0.01) and the anthropometric measurements. Test-retest reliability showed a good correlation coefficient (intraclass correlation=0.97). CONCLUSION: The Italian LDQ is a valid and reliable instrument for detecting and measuring functional disability in patients with ankylosing spondylitis. Our results confirm the utility of this questionnaire as a valid and feasible functional measure for patients with ankylosing spondylitis.

Adult↗

Surgical treatment of persistent type 2 endoleaks, with increase of the aneurysm sac: indications and technical notes.

OBJECTIVE: Unsolved type 2 endoleaks and aneurysmal sac increasing after endovascular aneurysm repair (EVAR) can be fixed with surgical sacotomy, ligation of the patent backbleeding vessels and preservation of the endograft. The aim of the paper is to highlight the technique as a feasible procedure in alternative to the removal of the graft. MATERIALS AND METHODS: Four male patients whose aneurysm sac maximum transverse diameter had increased by 5 mm or more, without evidence of endoleak, migration or structural alteration of the endografts. The surgical access was by medial laparotomy in one case, flank incision in two cases and mini-laparotomy with laparoscopic assistance in the fourth case. Patients were followed with spiral CT and duplex ultrasound at discharge and at 6-12 months. RESULTS: All procedures were carried out, without complication. Two patients required intensive care unit (ICU) admission and the average post-operative hospital stay was 10 days (range 6-13). All patients are currently alive with a functioning endograft, at an average follow-up of 14.7 months. CONCLUSIONS: Sacotomy, leaving the endograft in place, appears to be a feasible therapeutic option, less invasive than conversion to open repair. This technique merits further study.

Aged↗

Gene therapy in peripheral artery disease.

In the last decade, studies of the biological mechanisms underlying angiogenesis, i.e. the development of a new vasculature from pre-existing blood vessels, have suggested a new approach to peripheral obstructive artery disease based on the treatment of ischemic tissues with angiogenic growth factors. As demonstrated by experimental studies in animal models, a therapeutic effect can be reached as the newly formed vascular network, functioning as a biologic by-pass, restores a normal blood supply to the ischemic territories. New techniques of gene therapy proved effective in reaching sustained concentrations of angiogenic factors in the target tissues. This review concerns the pre-clinical background and the results of the early clinical trials of angiogenic gene therapy, which have shown the safety and feasibility of this new approach.

Animals↗

Rational design of biologically active peptides: inhibition of T cell activation through interference with CD4 function.

In our laboratory we generated one synthetic cyclic peptide (Pep4) and tested it in human mitogen stimulation assays (MSA) and mixed lymphocytes reactions (MLR) generating dose-response curves showing a dose-dependent inhibition of MSA up to 80% and MLR up to 98%. MSA and MLR were repeated after pre incubation of the Pep4 with each separate responder cell subset and subsequent reconstitution: these experiments showed inhibition only when the peptide was present in culture. Pep4 showed species specificity since it was ineffective in inhibiting rat MLR. Combination effect analysis with Pep4 and cyclosporine showed a combination index > 1. This rationally designed peptide (Pep4) shows powerful inhibition of human T cell activation and, although the exact mechanism is still undefined, it seems to exert its major action on the T cell surface, interfering with co receptor interaction and disrupting the same activation signal pathway inhibited by cyclosporine A.

Animals↗

Transcriptionally active drugs improve adenovirus vector performance in vitro and in vivo.

Cytomegalovirus (CMV) promoter is often present in recombinant adenovirus vectors (AdVs) suitable for gene therapy, ensuring high levels of transgene production in a wide range of hosts. Despite this characteristic, the presence of the AdV genome in target cells and tissues typically lasts longer than transgene production that may be rapidly extincted by ill-defined silencing mechanisms. In the present article, it is reported that transcriptionally active drugs, retinoic acid (RA) and histone deacetylase inhibitor trichostatin A (TSA), enhance AdV transgene expression in infected cells and tissues. The association of RA and TSA increased more than seven-fold above control the activity of AdVs encoding for LacZ or VEGF165. This effect was, at least in part, mediated by the direct activation of retinoic acid receptors. Finally, administration of RA and TSA alone at days 0 and 5 after infection prolonged transgene production up to 21 days after infection versus 6-8 days in untreated controls. These results indicate that transcriptionally active drugs improve AdV function and may represent a novel strategy to more efficiently design AdVs for gene therapy interventions.

Adenoviridae↗

Rational design of biologically active peptides: inhibition of T cell activation through interference with CD4 function. Transplant Int (2000) 13 [Suppl 1]: S306-S310.

In our laboratory we generated one synthetic cyclic peptide (Pep4) and tested it in human mitogen stimulation assays (MSA) and mixed lymphocytes reactions (MLR) generating dose-response curves showing a dose-dependent inhibition of MSA up to 80% and MLR up to 98%. MSA and MLR were repeated after pre incubation of the Pep4 with each separate responder cell subset and subsequent reconstitution: these experiments showed inhibition only when the peptide was present in culture. Pep4 showed species specificity since it was ineffective in inhibiting rat MLR. Combination effect analysis with Pep4 and cyclosporine showed a combination index > 1. This rationally designed peptide (Pep4) shows powerful inhibition of human T cell activation and, although the exact mechanism is still undefined, it seems to exert its major action on the T cell surface, interfering with co receptor interaction and disrupting the same activation signal pathway inhibited by cyclosporine A.

Animals↗

Induction of interleukin-1beta and interleukin-6 gene expression in hypoperfused skeletal muscle of patients with peripheral arterial disease.

BACKGROUND: A growing amount of data supports the role of inflammation in the pathophysiology of atherosclerotic diseases but the cellular source of cytokines has not been clearly identified. Cytokines could be produced by inflammatory cells, activated endothelial and smooth muscle cells, and by the tissue exposed to recurrent ischemia. Accordingly, we evaluated whether hypoperfusion induces gene expression of interleukin (IL)-1beta and IL-6 in the skeletal muscle of patients with peripheral arterial disease and critical limb ischemia. METHODS: Skeletal muscle biopsies were obtained, during a femoral-distal bypass, from normoperfused (control) and hypoperfused skeletal muscles in 8 patients. Gene expression was assessed by semiquantitative reverse transcriptase-polymerase chain reaction, using glyceraldehyde-phosphate-deydrogenase mRNA levels as a normalization factor. RESULTS: In the hypoperfused biopsies, the level of IL-1beta gene expression was significantly higher in all but 2 patients (mean upregulation > 8.8 fold, p = 0.043), and the level of IL-6 gene expression was significantly higher in all but 1 patient (mean upregulation > 23.7 fold, p = 0.031). CONCLUSIONS: We report that IL-1beta and IL-6 gene expression is markedly upregulated in hypoperfused skeletal muscle of patients with critical lower limb ischemia. To our knowledge this is the first report of a local activation of the inflammatory cascade at the level of hypoperfused skeletal muscle. This activation, which could worsen symptoms and tissue viability and be involved in the pathophysiology of reperfusion injury, might be considered as a therapeutic target. It remains to be investigated whether our results may also apply to coronary artery disease.

Aged↗

Synergistic immunosuppressive actions of cyclosporine with a mouse anti-rat alpha/beta-T cell receptor monoclonal antibody.

A mouse IgG1 mAb (R73) directed against the rat alpha/beta-TCR was documented not only to prolong the survival of allografts across major RT1 plus non-RT1 antigenic disparities, but also to display a synergistic immunosuppressive interaction with CsA. Heterotopic cardiac transplants from Buffalo (RT1b) rats survived significantly longer in Wistar-Furth (RT1u) hosts treated immediately after the operation with 0.25 mg/kg R73 i.v., with a mean survival time of 11.0 +/- 5.5 versus 6.8 +/- 1.2 days in the untreated group (P < 0.01). Administration of 0.5 or 5.0 mg/kg R73 displayed dose-dependent prolongation of survival to 17.0 +/- 8.3 days (P < 0.05) or 28.6 +/- 14.0 days (P < 0.01), respectively. One 0.5 mg/kg i.v. dose of R73 delivered to normal Wistar-Furth hosts produced peripheral T cell depletion that reversed after 16 days. Three injections of 0.5 mg/kg R73 on days 0, 2, and 4 prolonged allograft survival to 52.5 +/- 38.6 days compared with 17.0 +/- 8.3 days with a single dose (P < 0.01). Addition of 3 daily doses of 5 or 10 mg/kg CsA administered per oral gavage to a single dose of 0.05, 0.25, or 0.5 mg/kg R73 injected on day 0 produced a synergistic effect to prolong allograft survival, as determined by the rigorous median-effect analysis. The synergistic interaction, which may be explained by the inhibitory effect of CsA on Ca(2+)-dependent pathways triggered after activation of TCR, the target of R73, warrants clinical investigation in order to assess the potential impact of anti-alpha/beta-TCR mAb on CsA-based immunosuppressive regimens.

Animals↗

Generation of oxygen free radicals during the metabolism of cyclosporine A: a cause-effect relationship with metabolism inhibition.

A better understanding of the mechanism of lipid peroxidation during the metabolism of cyclosporine A (CsA) might help explain the toxicities of this immunosuppressive drug on various organs. Our in vitro work used microsomes prepared from livers of phenobarbital-induced male rats. The incubations (total volume 1ml) also contained a NADPH regenerating system and substrate (i.e., CsA, carbon tetrachloride, or aminopyrine) dissolved in ethanol. Lipid peroxidation was inferred from the presence of malondialdehyde (MDA) which was detected by the thiobarbituric acid assay. The formation of CsA hydroxylated metabolites (AM9 and AM1) was monitored by liquid chromatography. The activity of the microsomal incubation was confirmed by measurements of MDA and formaldehyde production caused by increasing concentrations of CsA, carbon tetrachloride, and aminopyrine. The occurrence of hydroxylated metabolites was not coupled to the production of MDA. Aminopyrine could inhibit MDA production by CsA, but CsA could not reduce the formation of formaldehyde by aminopyrine. Erythromycin, a competitor for the binding site of CsA on cytochrome P450, reduced MDA production by CsA, and CsA inhibited formaldehyde production by erythromycin. Interaction studies with SKF 525A, ketoconazole, superoxide dismutase, catalase, alpha-tocopherol, and reduced glutathione confirmed the role of cytochrome P450 and the presence of activated oxygen species as a source of microsomal peroxidation which in return may explain the inhibitory effect of CsA on cytochrome P450 itself.

Aminopyrine↗

[Skin manifestations in 140 kidney transplants].

Cutaneous lesions can be a significant problem in kidney transplant recipients. The AA report a clinical spectrum of iatrogenic, infectious, preneoplastic and neoplastic skin diseases in 140 renal transplant recipients observed, from march 1988 to july 1991, at the Catholic University in Rome. Iatrogenic skin manifestations were the most common, followed by infections of the skin and preneoplastic and neoplastic cutaneous lesions.

Adult↗

The use of absorbable staples for construction of a bladder tube.

Stapling instruments have been widely used in general surgery but not in the surgical treatment of the urinary tract. The stapler Poly CS-57 (Auto Suture, U. S. S. C.) with absorbable staples has been evaluated in the construction of ten bladder tubes for ureteral substitution in three dogs and six pigs. The dogs and pigs were sacrificed at two, three and six months. There was no mortality rate, no infections, no suture leakages and no crystal or stone formation. There were three instances of ureterovesical anastomotic stenosis. It appears that the absorbable staple can be safely used in urologic operations and that the use of the Poly CS 57 stapler for the construction of a bladder tube makes the procedure safer, simpler and faster.

Absorption↗