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Biomedical subjects

G Simoni

Publications and source records attributed to G Simoni.

At least 55 records · Page 3Linked to original sources

Screening for abdominal aortic aneurysms and associated risk factors in a general population.

OBJECTIVES: To evaluate the prevalence of abdominal aortic aneurysms (AAA) in a general population and to compare the results with those of similar studies in other countries. DESIGN: Ultrasound screening study and collection of clinical and biochemical data. SETTING: An urban Health Service District in Genoa, Italy. MATERIALS: A general population, aged 65-75 years, invited by personal letter between 1991-1994. RESULTS: 1601 subjects (741 males and 860 females) out of 2734 invited (58.5%) were evaluated. According to the ultrasound findings, 27 patients (1.7%) had an aortic dilatation of 26-29 mm; an AAA of 30-39 mm was found in 37 (2.3%) and an AAA > or = 40 mm in 33 (2.1%). The overall prevalence for AAA was 4.4% (8.8% in males and 0.6% in females respectively). The prevalence of smoking, alcohol consumption, coronary heart disease, chronic obstructive pulmonary disease and arterial disease were significantly higher in patients with AAA (p < 0.01). CONCLUSIONS: Ultrasound screening for AAA is a reliable and useful method and should be focused on men, regardless of concurrent disease.

Aged↗

Protective effect of selenium on hemoglobin mediated lipid peroxidation in vivo.

The toxicity of hemoglobin (Hb) solutions is related, at least in part, to the generation of oxygen free radicals with consequent induction of lipid peroxidation. The present study was designed to examine whether selenium (Se) may prevent the oxidative damage observed after Hb administration. Three groups of rats were compared; (I) the negative control group receiving autotransfusion; (II) the positive control group with replacement of 40% total blood volume (TBV) with modified bovine Hb solution; and (III) the experimental group which received dietary supplemented selenium (Na2SeO3) in daily doses of 5 micrograms.kg body wt-1 in drinking water, 4 days before and 3 days after administration of Hb solution in the same volume as in group II. Three days after Hb injection, all animals were sacrificed. Oxidative stress was determined by measuring conjugated dienes (CD) and thiobarbituric acid reactants (MDA) in homogenates of the perfused liver, heart, lungs, kidney, brain and plasma. Additionally, the 45k x g supernatants of the organs homogenates and plasma were assayed for the antioxidant enzymes activity: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and the intracellular level of reduced glutathione (GSH). Also, a measurement of nonprotein bound intracellular free iron (Fe) and tissue Se concentrations was performed. Simultaneously, injury dysfunction of vital organs was assessed by the measurement of plasma LDH, SGPT, creatinine, blood PaO2 and by histopathological studies. Results indicate that the exchange transfusion with Hb solution introduced significant increases in CD and MDA formation, particularly in the liver and heart tissues, and in plasma. While the values of the SOD and CAT in the liver and heart tissue were generally altered, the SOD/CAT ratio was also increased. After the Hb injection, activity of GSH-Px remained unchanged and was associated with significant depletion of GSH. The plasma levels of SGPT and LDH were increased, but the creatinine and PaO2 was similar to that of the control and corresponded with histopathological findings. The liver and heart intracellular free Fe was found to be higher than that of control. Treatment with Se was very effective in the prevention of oxidative damage introduced by Hb. Full protection from MDA formation was noted in liver tissue (p < 0.001). Also, plasma levels of MDA, SGPT and LDH were significantly decreased and appeared similar to that of the control group (I). Treatment with Se increased liver (p < 0.05) and plasma (p < 0.1) level of GSH-Px.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Prevention of vascular intimal hyperplasia in small caliber prostheses. Preliminary results].

Intimal hyperplasia is one of the main risk factors for the patency of small diameter bypass grafts. The standard unfractioned heparin (UH) is able to control this phenomenon but the clinical use is not fit for long term treatment; on the other hand the antiplatelet drugs have an anti-thrombotic effect but they seem to be unable to control intimal hyperplasia. Low molecular weight heparins (LMWH) have an anti-thrombotic effect superimposable to that of UH with minimal side-effects and might inhibit intimal hyperplasia too. Based on these criteria, we carried out an experimental study on sheep with the aim of evaluating the efficacy of postoperative treatment with LMWH versus an anti-platelet drug in controlling intimal hyperplasia and growth of true endothelial cells in small prosthetic ePTFE grafts (4 mm) interposed in the carotid artery. At the operation, 30 sheep were randomly located in 3 groups: A = control group, no treatment; B = Ticlopidine hydrochloride 250 mg/bid by mouth for 4 weeks; C = LMWH 3.075 IU AXa (0.3 ml) sc preoperatively and then once a day for the same period. Complete thrombosis of the graft occurred in 7 sheep of group A, 5 in B and 2 partial in group C. The intimal hyperplasia was moderate-severe in group A, mild-moderate in group B and no-mild in group C. True endothelial cells were found mainly in the LMWH group; in the other groups and in other portions of the grafts the cellular coverage was accomplished almost completely by fibroblasts. The study is still in progress with 6 further sheep treated with LMWH.

Animals↗

Chromosome 14 maternal uniparental disomy in the euploid cell line of a fetus with mosaic 46,XX/47,XX,+14 karyotype.

We investigated the parental origin of the extra chromosome 14 and of the two chromosomes 14 of the euploid cell line, in a case of fetal mosaicism 46,XX/47,XX+14 diagnosed at amniocentesis. Molecular analysis of five polymorphic loci of the short tandem repeat type was performed. Markers D14S43 and D14S49 showed the presence of maternal uniparental disomy of chromosome 14 in the apparently normal cell line. The distribution of the markers analysed along the chromosome suggests maternal heterodisomy with a large isodisomic segment in the telomeric region, possibly caused by meiotic crossing-over.

Adult↗

Pelvic perfusion in the adjuvant therapy of locally advanced rectal cancer. Feasibility trial and initial clinical experience.

PURPOSE: The increased risk of pelvic recurrence in patients with locally advanced rectal cancer seems to justify a more aggressive regional therapeutic approach. In this attempt a feasibility study has been recently activated on hyperthermochemotherapeutic pelvic wash in patients with resectable, locally advanced, cancer of the distal rectum. METHODS: Two alternative methods of hyperthermochemotherapeutic pelvic wash have been used in sequence. In the first method 3000 ml of warm (45 degrees C) saline solution containing 30 mg of mitomycin C were injected into the pelvis both intraoperatively and in the immediate postoperative period. In the second method a 60-minute perfusion of the pelvic space with 2000 ml of heated (45 degrees C) saline solution with 40 mg of mitomycin C was provided intraoperatively using an extracorporeal circuit. RESULTS: Four patients submitted to abdominoperineal amputation with pelvic lymph node dissection have been treated following one of the two methods. No complications related to the treatment occurred. Either the first or the second hyperthermochemotherapeutic pelvic wash method showed a high regional pharmacokinetic advantage with a perfusate/blood "AUCs" ratio of 576 and 374, respectively. CONCLUSIONS: The potential role of hyperthermochemotherapeutic pelvic wash as an additional regional treatment in locally advanced rectal cancer and the differences between the two methods, in our limited experience, are discussed.

Aged↗

First-trimester human trophoblast is class II major histocompatibility complex mRNA+/antigen.

Lack of expression of the polymorphic class I and class II MHC antigens in the cytotrophoblast is one of the major factors determining the privileged immunologic status of the placenta. In this report, we show that first-trimester human placental cytotrophoblast cells display moderate to strong expression of class II MHC (HLA-DR alpha and -DR beta) and Ii chain transcripts, apparently in absence of detectable class II antigens and Ii chain. In addition, DR alpha, DR beta, and Ii mRNAs, but not antigens, are consistently upregulated by IFN-gamma. Constitutive expression and upregulation of mRNAs are detectable in trophoblast cells kept in short term as well as prolonged (2-3 weeks) culture. These results are reminiscent of an analogous mRNA+/antigen- dissociation occurring, in the case of class I MHC gene products, in a subpopulation of first-trimester cytotrophoblast cells. Thus, analogous mechanisms prevent the expression of potentially hazardous class I and II allodeterminants at early stages of semiallogeneic pregnancy.

Blotting, Northern↗

Cytokines and PAF release from human monocytes and macrophages: effect of hemoglobin and contaminants.

Monocytes [M] were isolated from venous blood of healthy volunteers and activated macrophage-leukocytes (Mø-L] were obtained from peritoneal fluid of patients with mild endometriosis. The M were incubated with pyrogen free CELLGRO culture medium [Control], and with 0.2 mM of [A] unmodified bovine hemoglobin (UHb), [B] Hb crosslinked to form polymers with M.W. < 400 kDa (LMWHb), [C] Hb crosslinked to form large polymers (< 1,020 kDa) (HMWHb), and Mø-L additionally with [D] UHb contaminated with endotoxin (Hb+E) (2.5 EU/mL), and [E] UHb contaminated with phospholipids (Hb+PLs). The Mø-L medium of incubation was tested for TNF alpha, IL-1 alpha, IL-6, GM-CSF and PAF after 6 and 24 hours, but M for TNF alpha and GM-CSF at 12, 24 and 36 hours. Mø-L were found more responsive than M colonies. The strongest reaction of Mø-L was to Hb+E, which produced levels of cytokines and PAF higher than Controls (p < 0.001). Hb+PLs induced smaller increases of TNF and IL-6, and a decrease in the levels of IL-1 and GM-CSF. However, the release of PAF was much greater with this Hb than with Hb+E. UHb caused an increase in TNF, as compared to control (p < 0.01). LMWHb generated a similar increase in TNF, but also a decrease in IL-1. Both polymerized Hb forms inhibited expression of GM-CSF. HMWHb induced high levels of TNF, IL-1 and PAF. UHb, LMWHb and HMWHb significantly increase levels of TNF in M cultures after 36 hours of incubation.

Animals↗

Reaction of human endothelial cells to bovine hemoglobin solutions and tumor necrosis factor.

Human umbilical vein endothelial cells (HUVEC) were incubated for 24 hours with 0.1 mM or 0.3 mM of: [A] unmodified (U) Hb-FeIIO2; [B] UHb-FeIII; [C] UHb-FeIV-OH; [D] polymerized low molecular weight Hb (< 400 kDa); [E] polymerized high molecular weight Hb (< 1,020 kDa); [F] polymerized low molecular weight Hb + Endotoxin (2.5 EU/mL); [G] rTNF alpha 100 pg/mL; [H] rTNF alpha 400 pg/mL; [I] rTNF alpha 800 pg/mL. The medium of the incubation was tested for LDH (index of cell injury), and for cytokines GM-CSF and IL-1 alpha released by the cells. The data suggests that oxidation status of the iron in the Hb molecule and concentration of Hb play an important role in causing EC injury. The highest toxicity was observed when EC were incubated with 0.1 mM of UHb-FeIV-OH (ferryl-Hb) and no toxicity with 0.3 mM of Hb-FeIII (ferric-Hb). The direct stimulation of EC by Hb for the production of IL-1 was limited, related only to high molecular weight Hb polymers or to Hb+E, however GM-CSF expression was increased by almost all Hb forms. TNF induced dose-related injury (R2 = 0.986), and dose-related release of IL-1 (R2 = 0.977). A different EC reaction was observed on the release of GM-CSF. Intermediate levels of TNF (400 pg/mL) increased the expression of this cytokine, while high levels (800 pg/mL) blocked its release.

Animals↗

[Screening for abdominal aortic aneurysms in the general population. Preliminary results].

Between March 1991 and April 1993, 1188 subjects aged 65-75 years, out of 2734 invited, underwent abdominal ultrasound for screening of asymptomatic abdominal aortic aneurysms (AAA). For each patient the maximal anteroposterior and transverse diameters of the suprarenal and infrarenal aorta were measured. According to the literature data an AAA is defined as an aortic dilatation > 29 mm. AAA < 40 mm are followed by ultrasound every 6 months and the AAA > 39 mm are considered for surgical repair after complete clinical work-up. In addition any aortic dilatation ranging 26-29 mm is followed too, using the same criteria. The aorta was normal in 1112 patients (95.12%), an infrarenal aortic dilatation was found in 21 patients (1.79%), an AAA < 40 mm in 15 patients (1.28%) and an AAA > 39 mm in 21 patients (1.79%). The global prevalence of AAA > 29 mm was 3.07% (0.3% for the females and 6.8% for the males), similar to that reported by other authors. The statistically significant (p < 0.01) risk factors were: smoking, alcohol consumption, coronary disease and chronic lung obstruction. Hypertension and dyslipidaemia were not significant (but HDL-cholesterol and Apo-B), according to a different etiology of the aneurysms. In addition 38.5% of the patients had total cholesterol > 240 mg/dl but only 34.9% of these was under medical treatment and/or on a diet. Our preliminary data confirm the results of similar studies in other countries: screening for AAA is worthwhile on the general population and, looking to a better cost-benefit rate, it might be focused only on males.

Aged↗

End-to-end arteriovenous fistula for chronic haemodialysis: 11 years' experience.

Between January 1979 and December 1989, an end-to-end arteriovenous fistula for chronic haemodialysis was performed at the anatomical snuffbox in 140 patients with a mean age of 51 (range 14-81) years and at the wrist in 248 with a mean age of 53 (range 19-83) years. The choice of site depended on the characteristics of the vessels and on the arterial blood pressure. No operative mortality, major complications or side effects occurred. The primary median patency for the arteriovenous fistula at the anatomical snuffbox was 36 months with a patency rate of 77.3% at 1 year, 36.3% at 5 years and 18.9% at 10 years. For the arteriovenous fistula at the wrist the median patency was 64 months and the patency rate 75.5% at 1 year, 54.5% at 5 years and 30.7% at 10 years. The higher incidence of thromboses in the patients with a fistula in the snuffbox may reflect an excessive enthusiasm for this technique because of initially promising results.

Adolescent↗

[Smoking as a risk factor in arteriopathies].

Tobacco use represents the most powerful chemical addiction, which has been defined as "the inability to discontinue smoking" and it is one of the main cardiovascular risk factors. It produces alterations in platelet activity, blood viscosity and vascular wall and clinical signs related to the different vascular districts. The probability of carotid lesions increases up to 32% for 10 years/smoking and the progression of the disease is proportional to tobacco consumption; on the contrary smoking cessation may be helpful. Furthermore the risk of PAOD increases 2 to 9-fold, irrespective the number of cigarettes and these modify significantly the long-term patency of the femoro-distal reconstructions (57% vs 78% at 2 years). Very impressive indeed the data concerning major amputations (21% vs 2%) and the mortality rate for cardiovascular diseases (83% vs 33%) between smokers and non-smokers. For the abdominal aortic aneurysm too smoking represents the main independent risk factor and the mortality rate rises 6 to 25-fold compared to the normal population. The conclusions are obvious and can be shortly summarized in the following sentence: "Stop smoking and keep walking".

Adult↗

Cytogenetic abnormalities detected by direct analysis in a case of choriocarcinoma.

Malignant trophoblastic cells from a case of choriocarcinoma were cytogenetically investigated by direct analysis of fresh tissue from the tumor. To our knowledge, previous cytogenetic studies have been performed only on established cell lines. In this study, 54 metaphases were observed, of which 41 were fully karyotyped. Three chromosomally abnormal lines were identified. In all of them, trisomy 3 and 10, a supernumerary isochromosome 1q,i(1)(q10), an i(8)(q10) replacing one chromosome 8, and a marker chromosome were observed. In addition, involvement of chromosome 12 was observed in two of the three lines, trisomic in one and an i(12)(q10) in the other.

Choriocarcinoma↗

Applicability of DNA isolated from syncytiotrophoblast vesicles to gene amplification and molecular analysis.

Maternal contamination of fetal DNA represents a major problem when highly sensitive molecular techniques are used in the prenatal diagnosis of genetic diseases. For this reason, we have studied the possibility of using DNA isolated from syncytiotrophoblast vesicles as a target of gene amplification (PCR). Three PCR systems were selected which included a repetitive 149 bp fragment of the Y chromosome, the VNTR locus D1S80, and a portion of the beta-globin gene. The results of these experiments indicate that DNA isolated from syncytiotrophoblast vesicles is free of maternal contamination and is suitable for gene amplification and DNA analysis.

DNA↗

Frequency of chromosomal aberrations after exposure to gamma-radiation of human chorionic villi.

We investigated the chromosomal damage induced by in vitro exposure to gamma-rays of uncultured first trimester chorionic villi. Frequency and types of chromosomal aberrations at increasing doses of radiation have been evaluated on cytotrophoblast spontaneous metaphases obtained after a short term incubation. Our results indicate a direct correlation between radiation dose and aberration frequency.

Chorionic Villi↗

First-trimester prenatal diagnosis of Roberts syndrome.

We present a case of prenatal detection of premature centromere separation on chorionic villi sampled at 8 weeks' gestation from a woman at risk of recurrence of Roberts syndrome. The same cytogenetic characteristic was confirmed on amniocytes at 14 weeks when ultrasound examination showed morphological anomalies of the fetus. To our knowledge, this is the first report of early prenatal diagnosis of Roberts syndrome.

Abnormalities, Multiple↗

Genetic diagnosis by chorionic villus sampling before 8 gestational weeks: efficiency, reliability, and risks on 317 completed pregnancies.

Transabdominal chorionic villus sampling (TA-CVS) was attempted in 328 high-risk pregnancies at 6-7 weeks of gestation. Sampling was feasible in 97.7 per cent of cases; chorionic tissue specimens of more than 10 mg were obtained in 94.4 per cent of cases at the first needle insertion and in 100 per cent after a second attempt. Fetal karyotyping succeeded in 99.4 per cent of cases, while no diagnostic failures were reported in enzymatic and DNA analyses. Fetal loss rate in the first 4 weeks after CVS was significantly higher than in the later CVS series (7.2 vs. 2.5 per cent), but 50 per cent of losses were observed within 2 weeks in cases of inviable aneuploidies. A high incidence of severe limb abnormalities (1.6 per cent) was detected in pregnancies intended to continue, confirming the aetiological role of early CVS. Unclear visualization of the placental limits and poor control of the needle path are thought to be the main reasons for the vascular disruption of the chorionic plate, and thereby hypoxic embryo tissue damage. A better selection of cases, together with high-resolution vaginal ultrasound visualization, and analytical techniques requiring a minimal amount of tissue should avoid any teratogenic effect of early CVS.

Adult↗

Prenatal diagnosis of metabolic diseases on chorionic villi obtained before the ninth week of pregnancy.

Nine pregnancies at risk for various metabolic disorders were monitored by prenatal diagnosis on chorionic villi obtained between the sixth and ninth weeks of pregnancy. A diagnosis of an affected fetus was made in five cases (Sandhoff, Tay-Sachs (2), Pompe's, GM1), while metachromatic leukodystrophy, GM1 (2), and Pompe's were excluded in four cases. It is concluded that chorionic villi are a reliable tissue for prenatal diagnosis of metabolic disorders also when obtained before the ninth week.

Cerebroside-Sulfatase↗