Search PubMed⌕ Search

Biomedical subjects

G Mariani

Publications and source records attributed to G Mariani.

At least 163 records · Page 9Linked to original sources
PubMed1995

[The evolution of the therapeutic choice in patients with the outcomes of non-Q myocardial infarct: 2 periods compared].

BACKGROUND: Over the last years there has been a tremendous increase in coronary angioplasty procedures (PTCA), due to the availability of better materials and to the refinement of operators skill. It is not known however if this "PTCA boom" has modified our approach to the patients with particular clinical situations, such as those with non-Q wave myocardial infarction. The purpose of this study was to verify, in patients undergoing coronary angiography for clinical reasons after a non-Q wave myocardial infarction, the clinical decision concerning the therapeutical choice in two different periods (101 patients in 1988 vs. 102 patients in 1992). METHODS AND RESULTS: Patients in the two groups had similar clinical manifestations whereas patients observed in 1992 had more frequently 2-vessel disease than single vessel disease as compared to patients studied in 1988 (p < 0.05). The distribution of patients with normal coronary arteries or with 3-vessel disease was similar in the two periods. In 1988 medical therapy was the most recommended treatment at discharge (47%), followed by aorto-coronary bypass (29%) and coronary angioplasty (24%). On the contrary, in 1992 PTCA was performed in 48% of patients, medical therapy was recommended in 28% while the incidence of coronary surgery was reduced to 24% (p < 0.01). From a clinical point of view a significant increase in PTCA procedures was seen in patients presenting with unstable angina after the non-Q wave myocardial infarction (54% of these patients undergoing PTCA in 1992 vs. 30% in 1988, p = 0.03) and in patients with effort angina and a positive exercise test at low workload (53% of these patients undergoing PTCA in 1992 vs. 22% in 1988, p < 0.05). Moreover, in 1992 PTCA procedures increased in patients with single vessel disease (64% in 1992 vs. 49% in 1988) and in patients with 2-vessel disease (64% in 1992 vs. 9% in 1988). Therefore, in these patients the need of aorto-coronary by pass was reduced from 39% in 1988 to 19% in 1992 (p < 0.05). The success rate of PTCA procedures was 98% in 1992 and 83% in 1988. No major complications were observed in the two study periods and no patients underwent urgent coronary surgery. CONCLUSIONS: These data show an increase in PTCA procedures over the last years in patients undergoing coronary angiography for clinical reasons after a non-Q wave myocardial infarction. The greater experience of operators allowed for improved results, thus reducing the need of coronary surgery in these patients.

Adult↗
PubMed1994

Efficient transfer of selectable and membrane reporter genes in hematopoietic progenitor and stem cells purified from human peripheral blood.

We have utilized highly purified hematopoietic progenitor and stem cells (HPCs, HSCs) from normal peripheral blood to develop methodology for: (a) efficient transfer into HPCs of a non-hematopoietic membrane reporter, i.e., the nerve growth factor receptor complementary DNA; and (b) effective gene transduction of putative HSCs, i.e., cells initiating Dexter-type long-term culture (LTC-ICs). Purified HPCs induced into cycling by growth factors (interleukin 3, interleukin 6, c-kit ligand) were transduced with the N2 retroviral vector containing the neomycin resistance (neor) gene. More than 80% of transduced HPCs were resistant to the toxic G418 level. Thereafter, the HPCs were effectively transduced with the LNSN retroviral vector containing a nerve growth factor receptor complementary DNA; the nerve growth factor receptor was detected on > or = 18% of the transduced HPCs. These experiments provide a new tool from which (a) to monitor expression of a transduced membrane report on hematopoietic cells, particularly at the level of HPCs/HSCs, and (b) to characterize the transduced cells by double- and triple-labeling membrane antigen analysis. Purified HPCs/HSCs grown in Dexter-type LTC were transduced at 1 week by exposure to supernatant N2 retroviral particles in the absence of exogenous hematopoietic growth factors. The procedure, devoid of toxic effects, allowed an efficient neor transduction into LTC-ICs. Thus, we consistently detected neomycin-resistant mRNA in the clonal progeny of HPCs produced in LTC at 5-8 weeks in both the nonadherent and adherent fractions; this timing of expression coincides with that of HPC production by LTC-ICs, thereby indicating the effective transduction of the LTC-ICs. These experiments represent a first step toward development of preclinical models for gene transfer into human peripheral blood HSCs by complex retroviral vectors.

Adult↗
PubMed1994

Protein S and HIV infection. The role of anticardiolipin and anti-protein S antibodies.

It has recently been reported that a large proportion of patients with HIV infection have low free protein S levels. In this study we show that protein S (PS) activity levels, as well as PS antigen (Ag), were significantly lower in 35 HIV-1 infected patients than in the control population (p < 0.001). When we divided HIV infected patients into three groups according to their CD4+ counts, we found that PS levels were significantly lower in patients with < 100 CD4+ cells/ul. In order to investigate the possible role of (auto)immune response in the pathogenesis of PS deficiency, the presence of anticardiolipin antibodies (aCL) and/or of the specific antibodies to protein S was evaluated. A high prevalence (77.1%) of aCL in both symptomatic and asymptomatic subjects was observed. The screening for specific anti-PS antibodies, performed by immunoblotting, showed an overall positivity of 28.6% in anti-HIV+ patients, with a higher prevalence in symptomatic than in asymptomatic patients. Interestingly, the prevalence of the positivity for anti-PS antibodies was found to be higher in anti-HIV+ patients with PS levels < 50%. Taken collectively, our findings suggest that at least one of the mechanisms through which PS levels are decreased in HIV infection, is due to the presence of specific autoantibodies.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Biodistribution and pharmacokinetic screening in humans of monoclonal antibody AR-3 as a possible immunoscintigraphy agent in patients with pancreatic cancer.

This pharmacokinetic study was performed in order to assess the potential usefulness of the murine monoclonal antibody (MoAb) AR-3-IgG1 as an immunoscintigraphy agent for pancreatic cancer. This MoAb, which defines a mucin-like antigen (CAR-3) expressed by a large fraction of pancreatic cancers, shows in fact favourable in vivo localizing properties in the experimental animal model of human tumor xenograft. 131I-AR-3-IgG1 was injected i.v. into 5 patients with suspected pancreatic cancer. Whole-body maps and spot views of the abdominal area were recorded with a computerized gamma-camera, and specific regions of interest drawn over the liver and spleen helped to define the kinetics of activity in these organs. Blood samples taken from 0.1-144 hours post-injection and daily urine collections over the same interval served to define the kinetics of plama distribution and removal of activity from the body. Different multicompartmental models were tested to fit the experimental data, assuming as the starting hypothesis that there was to be significant nonspecific tracer accumulation in the liver, spleen and bone marrow, as already observed for the majority of radioiodinated murine MoAbs injected into humans. Surgery confirmed pancreatic cancer in 3 out of the 5 patients (chronic pancreatitis and periampullary cancer in one each); in all these 3 patients immunostaining with the MoAb AR-3 demonstrated the presence of the CAR-3 antigen (with a cytoplasmic and endoluminal/secretory pattern of distribution). Nonspecific radioactivity accumulation in the liver, spleen and bone marrow was extremely low, linked essentially to the blood pool effect of circulating activity in these organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Critical evaluation of endothelins assay.

Endothelin(s) is (are) generally measured by highly-sensitive RIA (radioimmunoassay) or sandwich-EIA (enzyme immunoassay) methods after preliminary extraction and chromatographic purification using Sep-Pak C18 cartridges; however, there is no general consensus about the range of endothelin circulating levels in healthy subjects and patients. We have evaluated the analytical performance of two commercial RIAs for plasma endothelin-1 assay (supplied by Peninsula Laboratories, Belmont, California, and by Biomedica Gruppe, Biomedica Gesellschaft mbH, Vienna, Austria) in order to verify whether differences in extraction procedures, antibody affinities or standard preparations can explain the different results obtained by these two RIAs. The RIA kits tested in the present study showed some differences in the analytical performance; in particular, different antibody specificities have been observed. The concentration range of endothelin(s) assayed with an imprecision better than 15%, which can be considered the working range, was wider for the Peninsula than for the Biomedica kit (i.e. from 1.6 to 50 fmol/tube vs 0.7 to 10 fmol/tube), whereas the two RIA kits showed similar sensitivity (i.e. about 0.2 fmol/tube). Taking into account the working range and sensitivity of the two RIAs to measure with an acceptable error the samples of normal subjects and the most part of patients, > or = 3-ml volumes of plasma must be extracted by Sep-Pak C18 cartridges and then measured by RIA. Owing to the central role played by the endothelin superfamily in several pathophysiological conditions, it is important to have a reliable assay for the measurement of these peptides in biological fluids and tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Immune tolerance in hemophilia-principal results from the International Registry. Report of the factor VIII and IX Subcommittee.

40 Hemophilia Centers from the USA, Canada, Europe and Japan referred to the International Registry 204 patients with haemophilia A, treated by Immune Tolerance (IT) Protocols over the past two decades because of the presence of an inhibitor to FVIII. 82% of the patients were high responders, while IT was started with low levels of inhibitor (< 10 BU) in most (57.3%) of the cases. 69 patients (33.8%) were given the highest FVIII dosage (> or = 200 IU/kg/day), 71 (34.8%) intermediate dosages (50- < 200) and 64 (31.4%) the lowest dosages (< 50). Of 158 patients persevering with treatment long enough to judge the outcome thereof, 107 (67.7%) achieved tolerance, 12 (7.6%) had a partial response, while 39 (24.7%) did not respond. Multivariate logistic regression analysis showed that two variables were independently associated with the highest probability of success: the use of high dose protocols (> or = 100 IU/kg/day) (p < .0001) and the presence of low levels of inhibitor (< 10 BU) at enrollment (p = .004). The Kaplan-Meier inhibitor-free survival curve showed that tolerance is longlasting: only 1 out of 107 patients relapsed and the longest documented tolerant patient has been inhibitor-free for 16 years. 129 hemophiliacs were HIV Ab-negative at enrollment; of the 118 HIV-screened after the treatment, 18 (13.9%) were found to be HIV Ab-positive. IT can indeed modify the natural history of inhibitors to FVIII in hemophilia.

Adolescent↗
PubMed1994

Immunopurified clotting factor concentrates.

Monoclonally purified factor concentrates have been available for hemophilia treatment since the late 1980's. They are biochemically characterized by a high-degree of clotting factor (FVIII or FIX) purification and by the virtual lack of contaminants (immunoglobulins, fibrinogen and fibronectin). The purification procedure sharply reduces the viral load and increases the safety of the concentrate because of the viral inactivation procedures. Viral safety is demonstrated by prospective studies in previously untreated patients as well as by the huge amount of concentrates produced and used so far without reports of untoward side effects. Monoclonal concentrates are also safe in terms of inhibitor production: they do not elicit the appearance of inhibitors to either FVIII or FIX with increased frequency, as shown by data in published prospective studies. Prospective studies have recently demonstrated that the long-term administration of these high purity concentrates does not exert any side effects on the immune system in HIV-positive hemophiliacs. The FIX concentrate is also extremely safe in terms of thrombotic complications: the highly pure FIX does not activate blood coagulation. It has been shown that the monoclonally purified FIX concentrate caused no thrombotic events in high-risk surgical patients who had previously experienced such complications while on Prothrombin Complex Concentrates.

Antibodies, Monoclonal↗
PubMed1993

Effects of coronary angioplasty on left ventricular function.

It is well known that myocardial revascularization after successful coronary bypass surgery results in improved left ventricular function. Coronary angioplasty also results in successful revascularization, favorably affecting both stunned and hibernating myocardium. We studied 22 patients with chronic stable angina who underwent successful angioplasty for an isolated narrowing of the proximal or midportion of the left anterior descending artery. These patients also performed isometric exercises before and after angioplasty, which can be used to characterize left ventricular function. Revascularization after angioplasty induced an immediate improvement in left ventricular function in those patients with dysfunction secondary to hibernating myocardium. Further studies are needed to assess the possibility of the myocardial stunning phenomenon occurring after angioplasty in those patients without left ventricular improvement.

Angioplasty, Balloon, Coronary↗
PubMed1993

Tumor targeting potential and metabolism of 5-[125I]iodo-2'-deoxyuridine injected intratumorally in patients with breast cancer.

We have previously demonstrated the high tumor targeting potential of the thymidine analogue 125IUdR in experimental animal models following direct intratumoral or locoregional (intracavitary) administration. The aim of the present work was to evaluate the metabolism and selectivity (based on differential cell proliferation kinetics) of 125IUdR incorporation in patients with breast cancer following a similar approach. 125IUdR (4-8 MBq) was injected intratumorally by ultrasound-guided percutaneous injection in 7 patients with breast cancer 24 hours before ablative surgery. Blood and urine samples were collected up to 72 hours after injection and analyzed by HPLC using a C18 reversed-phase column and methanol:water (20:80) as the mobile phase. Following resection, the radioactivity of the tumor and the surrounding tissues was measured in a gamma counter, and microautoradiography was performed on semithin tissue sections to determine the site of tracer incorporation at the cellular level. Activity in plasma peaked at 0.5 to 1 hour after 125IUdR injection (4.96 +/- 1.08% of injected dose/liter), declining thereafter with a mean T1/2 of 11.24 +/- 2.78 hours. By HPLC analysis, undegraded 125IUdR was about 15-30% of total plasma activity, with a biphasic pattern peaking at both 1-3 hours and approximately 12 hours. In addition to free 125I-, about 10% of early plasma activity was constituted by a labeled metabolite (tentatively identified as radio-iodouracil), rising to about 50-60% at later time points. About 70-90% of urinary radioactivity was 125I-, and 5-20% was undegraded 125IUdR in the first 24-hour samples, while the remainder was iodouracil. High tumor/nontumor ratios were obtained (mean 147.4 +/- 125.2, range 27-397) with average tumor/blood ratios at the time of surgery equal to 32.7 +/- 18.6 (range 5-56). An average 0.0244 +/- 0.0189% of the injected dose was present per gram of tumor (range 0.001-0.061% ID/g). Microautoradiography confirmed the high values of tumor/nontumor incorporation ratios and demonstrated the specificity of 125IUdR incorporation mostly in the tumor cell nuclei, with only occasional incorporation by normal-appearing tubular cells. These results suggest the potential of radiolabeled IUdR for tumor targeting in humans, to be used whenever a satisfactory route of locoregional administration allowing for homogeneous tracer distribution within the tumor mass is accessible and in the presence of favorable tumor cell proliferations kinetics.

Aged↗
PubMed1993

Transforming growth factor-beta potentiates vitamin D3-induced terminal monocytic differentiation of human leukemic cell lines.

We have investigated the effects of 1,25-dihydroxyvitamin D3 (D3) and/or transforming growth factor (TGF)-beta on one monocytic (U-937) and two human promyelocytic (HL-60 and AML-193) leukemic cell lines. D3 addition induces a partial monocytic maturation of the cell lines, whereas TGF-beta treatment is largely ineffective. Combined treatment with TGF-beta and D3 causes terminal monocytic maturation, as evaluated both by assessment of a large spectrum of membrane Ag and by functional assays. Furthermore, sequential addition of the two inducers showed that pretreatment with TGF-beta 1 followed by incubation with D3, but not vice versa, induces monocytic maturation as effectively as simultaneous treatment with both agents. In liquid culture the proliferative activity of these cell lines is slightly decreased by D3 and virtually unaffected by TGF-beta, whereas combined treatment with D3 and TGF-beta induces a markedly potentiated inhibitory effect. Furthermore, TGF-beta/D3 treatment (but not D3 alone) elicits the expression of membrane CD14, FcRI, FcRII, CD11a, CD11b, CD11c, ICAM-1, and PECAM-1 Ag at a level comparable to that observed on normal human monocytes. It is noteworthy that several of these Ag play an important role in monocyte physiology (e.g., CD14 Ag mediates the binding of bacterial LPS to monocytes). Treatment with both TGF-beta and D3 (but not D3 alone) induces superoxide anions and H2O2 production similar to that of circulating monocytes. In semisolid culture, D3 and TGF-beta alone cause, respectively, a marked and slight loss of cloning efficiency of the cell lines, whereas their combined addition synergistically results in a complete loss of the cloning capacity. These findings suggest a physiologic role for TGF-beta in monocyte maturation. Furthermore, they may pave the way to the design of clinical protocols combining D3 and TGF-beta in the differentiation therapy of acute promyelocytic/myelomonocytic leukemia.

Adjuvants, Immunologic↗
PubMed1993

Molecular analysis of factor VII deficiency in Italy: a frequent mutation (FVII Lazio) in a repeated intronic region.

Molecular defects and polymorphic haplotypes of coagulation factor VII gene were studied in eight unrelated Italian subjects with factor VII deficiency, seven having the factor VII- variant, one the factor VIIR variant. An intron 7 mutation, which alters the consensus donor splice site sequence, was found in six subjects. The presence of the founder effect is suggested by their common geographical origin (a mountain area in the Lazio region) and by the identical polymorphic haplotype underlying the mutation. A different mutation, also located in the 5' monomer of the repeated intron 7 sequence, was found in the heterozygous condition in a subject from Northern Italy. New polymorphic alleles were detected in the repeated intron 7 region in subjects from Eastern Africa. Two missense mutations in codon 97 (Gly-->Cys, Gly-->Ser), the first found in the compound heterozygous condition with the frequent intron 7 mutation, suggest the presence of a hot spot mutation site in the second epidermal growth factor domain. Two neutral dimorphisms at codon 333Ser and 115His were detected, the last in linkage disequilibrium with the 353Arg/Gln polymorphism, and showing differences in frequency in the FVII deficient and control subjects.

Base Sequence↗