Search PubMed⌕ Search

Biomedical subjects

G Fiorelli

Publications and source records attributed to G Fiorelli.

At least 127 records · Page 7Linked to original sources

Cerebrovascular disorders and alcohol intake: preliminary results of a case-control study.

The role of alcohol as a risk factor for cerebral infarction and hemorrhage has been assesed in 200 middle-aged and elderly stroke patients and 200 controls matched for age, sex and hospital admission date. Computed tomographic brain scans were done in all but 10 of the stroke patients. Alcohol intake was reckoned on the 12 months preceding hospitalization and expressed in grams daily according to a standard nomogram. The Michigan Alcoholism Screening Test was used for the diagnosis of alcoholism. Cerebral infarction was present in 59% of the stroke patients and cerebral hemorrhage in 9%. The role of alcohol as risk factor for stroke proved to be small (Odds Ratio 1.86) and was practically lost after adjustment for the most common risk factors for cerebrovascular disorders (previous strokes, arterial hypertension, diabetes, obesity and hyperlipidemia). Our findings seem to suggest that alcohol is not an independent risk factor for stroke in the middle-aged and elderly. The data are, however, preliminary and are discussed in the light of methological problems.

Aged↗

Preclinical hypogonadism in genetic hemochromatosis in the early stage of the disease: evidence of hypothalamic dysfunction.

We studied endocrine functions at baseline and after TRH and LHRH stimulation in a group of 7 young male patients with genetic hemochromatosis (HE) without liver damage (i.e. fibrosis and cirrhosis). In five patients endocrine re-evaluations after complete iron depletion was also performed. Mean basal testosterone (T), FSH, LH and PRL were significantly lower than in controls. Serum T increased normally after HCG stimulation. The normal or high increments of LH after LHRH stimulation suggest that secretion capacity of LH was intact and that hypothalamic dysfunction could be responsible for the preclinical gonadal deficiency found in our patients. The response of PRL to TRH indicates that secretion capacity of lactotrophs although present, was decreased and did not improve after phlebotomy therapy. After iron depletion the two patients with the lowest basal T levels showed the highest increments indicating that in the early stages of hypothalamic-pituitary damage gonadal dysfunction is still reversible in HE patients.

Adult↗

Liver damage in Italian patients with hereditary hemochromatosis is highly influenced by hepatitis B and C virus infection.

We evaluated the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in 78 Italian patients with hereditary hemochromatosis as well as the relation between HCV antibody (anti-HCV) status, hepatitis B surface antigen (HBsAg) and liver histology. None of the patients had been transfused or ever consumed more than 60 g of alcohol per day. Eighteen showed histological signs of chronic hepatitis, active cirrhosis was present in 12, chronic active hepatitis in 4 and chronic persistent hepatitis in 2. Liver fibrosis or cirrhosis without inflammatory activity was observed in 31 subjects, whereas liver histology was normal except for iron overload in 18. The prevalence of HBsAg in the whole series was 5% and of anti-HCV was 20.5%. The prevalence of HBsAg and anti-HCV was significantly higher in the chronic hepatitis group than in the fibrosis/cirrhosis (p = 0.01) and the normal groups (p < 0.01). Fourteen of 18 hereditary hemochromatosis patients with chronic hepatitis were HBsAg (4) or anti-HCV (10) positive and all the latter subgroup had HCV-RNA in their serum as shown by the polymerase chain reaction. Although most of the patients with associated chronic hepatitis had cirrhosis, their serum ferritin levels and amount of mobilizable iron were significantly lower than those of the fibrosis/cirrhosis group (p < 0.01). This indicates that hepatitis viral infection acts synergistically with iron in accelerating the development of liver damage.

Adult↗

Uremic inhibitors of erythropoiesis: a study during treatment with recombinant human erythropoietin.

The effects of increasing amounts of uremic sera (US) on the growth of erythroid progenitor cells [burst-forming unit erythroid (BFU-E)] collected from peripheral blood of normal subjects were evaluated to assess the potential role of uremic inhibitors of erythropoiesis during a treatment with recombinant human erythropoietin (r-HuEpo). US were collected from 8 patients on regular dialysis with marked anemia (Hb 6 +/- 0.5 g%) before and after a treatment with high doses of r-HuEpo (from 300 to 525 U/kg/week). Standard cultures for BFU-E were performed in alpha-metylcellulose with fetal calf serum (FCS) and 4 U/ml of r-HuEpo (Cilag, Ortho). In successive cultures, US were added at increasing amounts to the standard culture in order to assess a possible inhibitory effect on BFU-E growth. Finally, in order to assess a possible lack of stimulatory factors, we partially substituted FCS with US. The addition of US collected either before or after therapy with r-HuEpo to the standard culture had no effect on the growth of BFU-E. Vice versa, the number of cultured BFU-E decreased when FCS was partially substituted with US collected before r-HuEpo. This effect was not evident when FCS was partially substituted with US collected after r-HuEpo. No significant differences were recorded in the tested sera collected before and after therapy considering erythropoietin levels and amino acid levels. We hypothesized that some other factors with erythropoietic stimulatory activity (burst-promoting activity?) may be deficient in uremic patients with marked anemia and can be induced during therapy with r-HuEpo.

Adult↗

Circulating burst-forming-unit erythroid and the responsiveness to recombinant human erythropoietin in patients on regular hemodialytic treatment.

The dose of recombinant human erythropoietin (r-HuEpo) required to correct anemia of end-stage renal disease varies among patients. The possible factors that interfere with the responsiveness to r-HuEpo were not completely known. In 32 patients on regular hemodialytic treatment with marked anemia (Hb 5.6 +/- 0.7 g/dl), we evaluated circulating erythroid progenitor cells [burst-forming-unit erythroid (BFU-E)], erythropoietin, ferritin, folate and 1-84-parathormone levels before r-HuEpo therapy. In 12 patients, the aluminum levels after deferoxamine were also evaluated. The possible correlation between these factors and the response to r-HuEpo therapy was then evaluated. The number of circulating (c) BFU-E was highly variable (521 +/- 447 colonies/ml of blood; normal level 742 +/- 192) and does not correlate with erythropoietin, ferritin, folate, 1-84-parathormone or aluminum levels. A direct correlation between basal cBFU-E and the responsiveness to r-HuEpo therapy was recorded while no correlation was found with the other analyzed parameters. We hypothesized that low basal cBFU-E (interleukin-3 deficiency?) could reduce the response to r-HUEpo because of failure of this hematopoietic stem cell compartment to replenish the pool of more mature erythropoietic progenitor cells during the phase of accelerated maturation induced by r-HuEpo.

Anemia↗

[Morphofunctional correlations in children with upper maxillary endognathia].

In this study 23 oral breathing children suffering from maxillary hypoplasia (endognathia associated with skeletal class II or III), selected for rapid maxillary expansion (RME) have been investigated by active anterior rhinometry. None of these patients presented O.R.L. pathologies during clinical examination except for some sporadic cases of adenoid hypertrophy (5 cases). Rhinomanometric and cephalometric examinations carried out before and after RME treatment showed a good correlation between the nasal respiratory function parameters and the structural cephalometric elements investigated by means of teleradiography. In particular, an important reduction in nasal respiratory resistance in all patients with conversion from oral to nasal respiration in the majority of cases corresponds, together with cross-bite resolution, to increased transversal dimension of the maxilla produced by RME. A clear regression in adenoid hypertrophy, where present, is also noted without any type of O.R.L. treatment. The improved respiratory situation could therefore produce benefits on the trophism of the nasal mucous and the lymphatic rhinopharyngeal tissue. Agreement between clinical, radiological and rhinomanometric findings confirm the usefulness of this method in diagnosing and following-up patients with this problem.

Adolescent↗

[Thoracic localizations of extramedullary erythropoiesis].

A series of 8 patients affected with hemolytic beta thalassemia with intrathoracic extramedullary hematopoiesis is reviewed. All patients were studied with conventional radiologic techniques and with CT and MR imaging. There was good correlation between conventional radiology findings and MR and CT results. CT and MR imaging were useful to evaluate not only the topographic localization of the masses of extramedullary hematopoiesis, but also their functional status. On CT, masses in the active phase exhibit high density and marked enhancement after i.v. administration of contrast medium; in the remission phase, the masses are hypodense, due to fat substitution, and unenhanced. On MR images, the active phase is characterized by a relatively low signal in both T1 and T2, while in the remission phase high signal is observed in both T1 and T2. A sign is seen on MR images which is considered as pathognomonic: a peripheral ring with high signal. The use of CT and MR imaging allows detailed information on the evolution of the hemolytic disease to be obtained. These pieces of information cannot be obtained with conventional radiology, which allows, at any rate, the correct diagnosis to be made.

Adult↗

Specific binding sites for H-ferritin on human lymphocytes: modulation during cellular proliferation and potential implication in cell growth control.

Interactions between human recombinant H- and L-ferritins and human lymphocytes were studied in vitro by direct binding assays and by flow cytometry. L-ferritin did not cause detectable specific binding, whereas H-ferritin showed a specific and saturable binding that increased markedly in phytohemagglutinin (PHA)-stimulated cells. This ferritin bound up to 30% of CD4+ and CD8+ T-lymphocytes and most B cells, indicating that expression of ferritin binding sites is not related to cell lineage or function. Dual-color flow cytometry experiments showed that ferritin binding sites were present on cells expressing the proliferation markers HLA-DR, MLR3, interleukin 2 (IL-2), and transferrin receptors (Tf-R). In addition, after PHA induction, the time course of the expression of H-ferritin binding sites was similar to those of the above proliferation markers. Ferritin binding sites were observed in lymphocytes at all cell cycle phases, including the early S-phase. H-Ferritin at nanomolar and picomolar concentrations had an inhibitory effect on PHA-induced blastogenesis. We propose that H-ferritin binding sites behave like proliferation markers, with the unusual function of downregulating proliferation.

Antigens, Surface↗

Effect of estrogens and progesterone on human peripheral erythroid burst-forming unit (BFU-E) growth.

Variations in the number of peripheral burst-forming unit--erythroid (BFU-E) of healthy women were observed during a prolonged period of observation. These differences were related to different phases of the menstrual cycle. A peak in the number of BFU-E occurred on day 14 of the cycle corresponding to the serum 17-beta-estradiol peak. The effect of estrogens and progesterone on the in vitro growth of peripheral BFU-E of healthy women was assayed. Estrogens demonstrated a stimulatory and progesterone an inhibitory effect in total lymphomonocyte cultures, whereas neither hormone had an effect in monocyte-depleted cultures. Prostaglandin E1 (PGE1) which is known to be secreted by monocytes, stimulated the in vitro growth of peripheral BFU-E. These data suggest that estrogens and progesterone could have a role in the in vitro growth of peripheral BFU-E, probably mediated by monocytes.

Adult↗

Growth factors in the human prostate.

Recent studies have focused on the potential role of local polypeptide growth-regulating factors in the etiology of benign prostatic hyperplasia (BPH) and prostatic carcinoma. In our studies we confirmed the presence of specific receptors for epidermal growth factor (EGF) in prostatic tissues from patients affected by BPH. In addition, we demonstrated that specific receptors for insulin-like growth factor type I (IGF-I) are present in BPH tissues. In order to identify a possible interaction between androgens and these growth-regulating factors, we investigated the effect of testicular suppression-induced androgen withdrawal on both EGF and IGF-I receptor concentrations in prostatic tissue from patients affected by BPH treated with a long-acting luteinizing hormone-releasing hormone analog. Both EGF and IGF-I binding capacities were significantly increased after treatment. This finding suggests that in vivo IGF-I and EGF receptor levels may be under negative androgenic regulation, indicating a potential role for these growth-regulating factors in the mechanism of response to the castration-induced regression of androgen-dependent prostatic tissue. Moreover, preliminary studies indicate that in human BPH prostatic tissue multiple IGF-binding proteins (IGF-BP) are present. This finding suggests a possible role of IGF-BP in modulating IGFs biological activities at the prostate level.

Aged↗

Cardiac alterations in 36 consecutive patients with idiopathic haemochromatosis: polygraphic and echocardiographic evaluation.

Thirty-six consecutive patients with idiopathic haemochromatosis (IH) were studied by electrocardiography (ECG), polygraphy, M-mode and 2-D echocardiography and Doppler-echocardiography. No significant correlations were found between ECG, PEP/LVET ratio and echocardiographic measurements. Left ventricular (LV) enlargement with impaired LV systolic function was present only in three patients (5.5%), of whom two died during iron-depleting therapy because of cardiovascular complications. Compared with controls, echocardiographic abnormalities were significantly more frequent and marked in subjects with higher iron overload than in those in whom it was lower. Ten patients were studied before and after iron depletion, nine of whom had only mild echocardiographic abnormalities at baseline examination. Significant reduction of end-diastolic thickness of the interventricular septum and LV mass (P less than 0.01 and less than 0.02 respectively) was observed. Also the end-diastolic thickness of the LV posterior wall and the end-systolic diameter of the left atrium reduced although not to a significant degree. The increased thickness of ventricular walls without impairment of LV systolic function is probably the first and still reversible cardiac alteration due to iron deposition in the myocardium. Later, with increasing iron overload, LV function becomes impaired and dilated cardiomyopathy develops. Early diagnosis and treatment of IH cardiopathy is needed before irreversible cardiac damage occurs.

Adult↗

Insulin-like growth factor-I receptors in human hyperplastic prostate tissue: characterization, tissue localization, and their modulation by chronic treatment with a gonadotropin-releasing hormone analog.

Insulin-like growth factor I (IGF-I) receptors were characterized in membranes obtained from prostate tissue of patients affected by benign prostatic hyperplasia (BPH) before and after treatment with a GnRH agonist analog. Binding of [125I]IGF-I to membranes obtained from untreated patients was specific and time and temperature dependent. Analysis of the binding data yielded two classes of binding sites, one of high affinity (Kd, 10(-11) mol/L) and one of lower affinity (Kd, 10(-9) mol/L). BPH membrane preparations were affinity-cross linked to labeled IGF-I, and then subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Analysis by autoradiography revealed one labeled protein with an apparent Mr = 300K under nonreducing conditions and two labeled protein with Mr = 270K and Mr = 130K under reducing conditions. Excess unlabeled IGF-II reduce both of them, whereas the same excess of IGF-I completely abolished them. In membrane preparations of prostatic tissues from patients affected by BPH and treated for 2 months with a GnRH agonist analog, the binding capacities of both binding sites were significantly higher than those of BPH tissue from untreated patients, whereas binding affinities were unchanged. The IGF-I receptor in BPH prostate tissue of untreated patients was mainly localized in the basal layer of the epithelium, as demonstrated by immunohistochemical staining, whereas in the tissue from treated patients positive staining was found also in the glandular epithelium. These results demonstrate that: 1) specific binding sites for IGF-I are present in prostatic tissue from patients with BPH, 2) androgen deprivation increases their binding capacities and seems to modify their epithelial localization.

Aged↗

Iron in the pathogenesis of hepatocellular carcinoma.

Several data indicate that iron may be involved in the pathogenesis of hepatocellular carcinoma (HCC). A high prevalence of HCC has been reported in patients with genetic hemochromatosis and the risk of HCC appears to be related to the amount and duration of iron overload. Iron, which has been demonstrated to facilitate persistent hepatitis B or C infection, could also act as a co-factor in the pathogenesis of HCC in patients with hepatitis B or C. Among the possible mechanisms by which iron could exert its cancerogenetic potential, free radicals production responsible for heritable genetic alterations appears to be one of the most important, although the fibrogenetic capability of iron, potentially leading to cirrhosis, cannot be underestimated.

Carcinoma, Hepatocellular↗