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Biomedical subjects

A Vignoli

Publications and source records attributed to A Vignoli.

At least 19 recordsLinked to original sources
PubMed2006

Blood oxidative status and selectins plasma levels in healthy donors receiving granulocyte-colony stimulating factor.

Recombinant human G-CSF (rHuG-CSF) is used for hematopoietic progenitor cells (HPC) mobilization and collection. Activation of polymorphonuclear leukocytes (PMN) is present during rHuG-CSF treatment and is associated with endothelial cell dysfunction and hypercoagulation. We evaluated whether PMN activation by rHuG-CSF may alter the blood oxidative status and subsequently affect the vascular cell function. Fourteen healthy individuals received rHuG-CSF for HPC harvesting. Blood was drawn before starting rHuG-CSF (T0), on the last day of rHuG-CSF (T1) and 1 week after stopping rHuG-CSF (T2). Levels of CD11b, myeloperoxidase (MPO), hydroperoxides, nitric oxide (NO), and soluble endothelium (sES), leukocyte (sLS), and platelet (sPS) selectins were measured. During rHuG-CSF, CD11b, MPO and hydroperoxides significantly increased, while NO levels significantly decreased, compared with T0. At T2 all these markers returned to baseline values. Significant increments of all selectins were observed during rHuG-CSF. At T2 sES and sEP significantly decreased back to pre-treatment values, whereas sLS remained significantly high. These data show that rHuG-CSF induces a transient inflammatory status characterized by circulating activated PMN, which release reactive oxygen species and intracellular proteases, promoting the onset of an abnormal oxidative status. This process may modify the hemostatic balance towards a pro-thrombotic state.

Adolescent↗
PubMed2003

Defibrotide reduces procoagulant activity and increases fibrinolytic properties of endothelial cells.

Defibrotide (DF), a polydeoxyribonucleotide with antithrombotic properties, has recently proven effective in patients with severe hepatic veno-occlusive disease (VOD), a life-threatening complication of high-dose chemo/radiotherapy regimens for stem cell transplantation. To understand the mechanism of its beneficial effect, we studied the impact of DF on the expression of tissue factor (TF) and fibrinolytic proteins (PAI-1 and t-PA) on endothelial cells. The in vitro response to DF of two types of human endothelial cells (ECs) of different origins, that is from macrovascular (HUVEC) and microvascular (HMEC-1 cell line) beds, was evaluated in the presence or absence of a proinflammatory stimulus (ie bacterial endotoxin, LPS). The results show that DF was able to significantly reduce the LPS-induced TF expression by HMEC-1, and less prominently by HUVEC. In addition, DF importantly influenced the fibrinolytic properties of both HMEC-1 and HUVEC. Specifically, it dose-dependently counteracted the LPS-induced increase in PAI-1 levels and decrease in t-PA activity expression. It also significantly incremented t-PA antigen in resting EC. Decreasing the procoagulant activity and increasing the fibrinolytic potential of EC favors an anticoagulant phenotype of the endothelium, which may protect from fibrin deposition and vascular occlusion.

Blood Coagulation Factors↗
PubMed2001

Symptomatic epilepsy with facial myoclonus triggered by language.

We report on a patient with a left frontal lesion who, many years after an injury, developed non-fluent aphasia and facial myoclonic jerks triggered by speaking and listening to spoken language. At age 57, the patient first noted that he would begin to stutter when delivering lectures at conferences. The stuttering would worsen if he continued talking. The video-polygraphic EEG recording shows brief paroxysms of spikes and polyspikes, followed by a slow wave, more evident in the left fronto-temporal region. The myoclonic jerks originating from the submental area correlate with EEG abnormalities. Clinically, these jerks determined a form of stuttering. The triggering factors were reading, speaking and listening to spoken language. This case had several characteristic features: facial myoclonus was the only seizure type experienced by the patient; the seizures and language impairment had a very late onset--about 50 years after the traumatic event that produced a dramatic lesion in the left fronto-polar region. (Published with videosequences.)

Aphasia, Broca↗
PubMed2000

Polymorphonuclear leukocyte activation and hemostasis in patients with essential thrombocythemia and polycythemia vera.

Thrombohemorrhagic complications are a major cause of morbidity and mortality in patients with essential thrombocythemia (ET) and polycythemia vera (PV). The pathogenesis of these complications is not completely clarified. Several studies have described abnormalities of red blood cells and platelets in these patients. However, no studies are available on changes in the polymorphonuclear leukocytes (PMNs), which can play an important role in the activation of the hemostatic system. In patients with ET (n = 37) and PV (n = 34), a series of PMN activation parameters (PMN membrane CD11b and leukocyte alkaline phosphatase [LAP] antigen expression, cellular elastase content, plasma elastase, and myeloperoxidase levels) was evaluated simultaneously with the levels of plasma markers of endothelial damage (thrombomodulin and von Willebrand factor antigen) and hypercoagulation (thrombin-antithrombin complex, prothrombin fragment 1 + 2, and D-dimer). The results show the occurrence of PMN activation in both groups of patients compared with a control group of healthy subjects. An increase in CD11b and LAP expression by PMN membrane was observed, together with a significant increase in cellular elastase content, plasma elastase, and myeloperoxidase levels. In addition, patients had high plasma levels of endothelial and hypercoagulation markers compared with controls. For the first time, these data show that in ET and PV, 2 hematologic conditions that place patients at increased risk for thrombosis, an in vivo leukocyte activation occurs and is associated with laboratory signs of endothelium and coagulation system activation. (Blood. 2000;96:4261-4266)

Adult↗
PubMed1999

Felbamate in refractory partial epilepsy.

This open-label study was performed to evaluate efficacy and safety of Felbamate (FBM) add-on therapy in drug-refractory partial epilepsy. We evaluated 36 patients (12 males) aged 11-68 years (mean 29.8) in which FBM was titrated gradually from 300 mg/day to a mean total maintenance daily dose of 1936 mg. Patients were monitored according to clinical practice and performed regularly laboratory tests. Mean follow-up of FBM therapy was 10 months (range 2-27). In this study, 5% of patients resulted to be seizure-free, 11% showed a seizure reduction more than 75%, 23% decreased their seizure frequency between 50% and 75% (P = 0.0001). The adverse events which were reported more frequently were: nausea, vomiting, anorexia and weight loss. Even if the patients sample is small FBM proves its efficacy in partial epilepsy, showing a relatively well tolerated profile.

Adolescent↗
PubMed1999

Intrauterine growth in the offspring of epileptic women: a prospective multicenter study.

The aim of the present study was to evaluate the risk of intrauterine growth delay in the offspring of epileptic mothers and to quantify the risks of intrauterine exposure to antiepileptic drugs (AEDs). Data concerning 870 newborns, prospectively collected in Canada, Japan and Italy, using the same study design, were pooled and analyzed. The overall proportion of newborns whose body weight (7.8%) or head circumference (11.1%) at birth were below the 10th percentile was not increased. However, logistic regression analysis showed that the risk of small head circumference was significantly higher in Italian than in Japanese (RR 4.2; 95% CI: 2.2-8.0) or Canadian children (RR 2.6; 95% CI: 1.1-6.5), and in children exposed to polytherapy (RR 2.7; 95% CI: 1.2-6.3), phenobarbital (PB) (RR 3.6; 95% CI: 1.4-9.4) and primidone (PRM) (RR 4.5; 95% CI: 1.5-13.8). Country was also the only factor affecting low body weight, with Italian children having a higher risk than Japanese (RR 5.2; 95% CI: 2.6-10.4) or Canadian (RR 8.8; 95% CI: 2.0-38.1) children. Due to the small categories, the influence of AED doses and plasma concentrations was studied for each individual AED, without adjustment for the other potential confounding factors. A clear dose-dependent effect was found for PB and PRM in terms of both small head circumference and low body weight, and a concentration-dependent effect for PB in terms of small head circumferences. The size of the difference between the Italian and the other two populations, which is only partially explained by differences in therapeutic regimens, suggests that genetic, environmental and ethnic factors also need to be taken into account when considering possible explanations.

Anticonvulsants↗
PubMed1999

Benign infantile familial convulsions: natural history of a case and clinical characteristics of a large Italian family.

We present a patient (3 months old) with partial and generalized seizures who has a family history of seizures with a onset during the first 12 months of life. We diagnosed benign infantile familial convulsions (BIFC) and we did not introduce any antiepileptic therapy. We present clinical data of her family where 18 out of 35 members were affected; to our knowledge this is the largest family with BIFC. BIFC is transmitted as an autosomal dominant trait; recently it has been reported that the gene for BIFC maps to the long arm of chromosome 19. We conducted linkage analysis in our family providing significant exclusion of linkage between the BIFC locus phenotype and chromosome 19 markers, suggesting that a second locus is involved in this family.

Child, Preschool↗
PubMed1999

Malformations in offspring of women with epilepsy: a prospective study.

PURPOSE: The incidence of malformations among infants of mothers with epilepsy treated with antiepileptic drugs (AEDs) during pregnancy is higher than that found in the general population. The aim of this study was to contribute to providing a definition of the rate of congenital anomalies in the offspring of mothers with epilepsy and to detect possible risk factors. METHODS: Since 1977, 517 pregnancies were followed up at the San Paolo Hospital in Milan by a team of epileptologists and obstetricians. The patients received monthly obstetric and neurologic examinations, and the blood levels of AEDs were tested monthly. During pregnancy the patients underwent ultrasound investigations to evaluate fetal morphology and development. At the time of delivery, the infants were submitted to a standardized examination by a pediatrician, and a more detailed clinical examination was performed on day 5. Malformations were classified as (a) genetic and chromosomic, (b) severe and mild malformations, and (c) deformities. RESULTS: The overall rate of malformations was 9.7%: of these, 5.3% were structurally severe, 2.2% were mild, 0.4% were chromosomic-genetic, and 1.8% were deformities. No malformation was detected in the 25 untreated patients. CONCLUSIONS: The risks of teratogenicity have been regarded as multifactorial, involving such factors as genetic predisposition, although most prospective studies show that AED-related factors are the primary risk factors for an increased incidence of congenital malformations.

Abnormalities, Drug-Induced↗
PubMed1998

Worsening in seizure frequency and severity in relation to folic acid administration.

We report a case of increase in seizure frequency and severity in a 26-year-old woman receiving folic acid at a dosage of 0.8 mg/day. She had symptomatic partial epilepsy with simple and complex seizures treated with carbamazepine. She was planning pregnancy and we prescribed folic acid for prevention of neural-tube defects. In the next few days she had a generalized tonic-clonic seizure for the first time and a significant increase in seizure frequency. Because of the temporal relation between the seizure worsening and the administration of folic acid, we hypothesize a role of folic acid in provoking seizures, as has been reported in the literature.Copyright Lippincott-Raven Publishers

Journal Article↗
PubMed1998

Chromosome 20 ring: a chromosomal disorder associated with a particular electroclinical pattern.

PURPOSE: The chromosome 20 ring [r(20)] is a rare chromosomal disorder without clear phenotypical markers. We describe the electroclinical pattern in a group of patients with r(20). METHODS: We observed 3 patients (a boy, patient 1; his mother, patient 2; and an unrelated man, patient 3), performing prolonged video-EEG and cytogenetic studies and fluorescent in situ hybridization (FISH) with chromosome-specific telomeric probes. RESULTS: All 3 patients had a very similar abnormal electroclinical pattern characterized by long bursts or trains of rhythmic theta waves, which were sharply contoured or had a notched appearance (with no detectable clinical correlate), and generalized spike waves (SW) associated with seizures of probable frontotemporal origin (SFT). In all 3 patients, the cytogenetic analysis of T lymphocytes showed mosaicism with a normal cell line and a second cell line with a chromosome 20, although the latter was little represented in patients 2 and 3. A few cells with a single chromosome 20 were also found. The same cytogenetic findings were confirmed in the lymphoblastoid cell line of patient 1 and in the fibroblasts of patient 3. FISH with chromosome-specific telomeric probes and TTAGGG sequences demonstrated the integrity of the ring chromosomes. CONCLUSIONS: The clinical picture of these patients appears to be related to the instability of the r(20)-generating cells monosomic for chromosome 20 and is thus haploinsufficient for a gene. In these patients, the electroclinical pattern of theta waves (probably unrelated to epilepsy) and the SW and SFT, even with mild mental retardation (MR) or no MR and without dysmorphic features, suggest that the r(20) syndrome may be present.

Adolescent↗
PubMed1997

Detection of circulating albumin-mRNA by RT-PCR does not indicate metastasizing hepatocellular carcinoma.

Hepatocellular carcinomas (HCC) frequently recur after partial liver resection or orthotopic liver transplantation, possibly because of the presence of a small number of hepatoma cells in the peripheral blood. Detection of circulating HCC cells might improve therapeutic options and could predict disease recurrence resulting from a metastasizing disease. In the present study, human albumin-mRNA was detected by RT-PCR in the peripheral blood of patients with hepatocellular carcinoma. Circulating albumin-specific PCR products were detected in each patient with HCC, but also in healthy volunteers. It is concluded that albumin-mRNA is not specific to circulating hepatoma cells and therefore does not indicate metastasizing disease.

Carcinoma, Hepatocellular↗
PubMed1996

Identification of subjects at risk for colorectal carcinoma through a test based on K-ras determination in the stool.

BACKGROUND & AIMS: The gold standard for screening for colorectal carcinoma is colonoscopy. The aim of this study was to compare endoscopic results with those obtained using the noninvasive screening test of K-ras determination in the stool in a large population of patients undergoing colonoscopy. METHODS: Two hundred thirty consecutive patients were studied by K-ras amplification on stool-derived DNA using polymerase chain reaction and oligomer-specific hybridization. RESULTS: Wild-type K-ras was amplified in 103 of 230 patients (44.8%), the rate of amplification being directly proportional to the presence of an organic disease of the intestine characterized by hyperproliferating mucosa. In 30 of these 103 patients (29.1%), a K-ras mutation was found. Four of 5 with early colorectal carcinoma, all who had K-ras mutations in the tumor, were identified. In first-degree relatives of patients with colorectal carcinoma, all subjects either carrying adenomas > 1 cm in diameter or multiple smaller adenomas were identified. In patients with inflammatory bowel disease, the test identified the only patient with neoplastic transformation. CONCLUSIONS: The sensitivity and specificity of K-ras determination on stool-derived DNA in patients with colorectal carcinoma, in first-degree relatives of patients with colorectal carcinoma, and in patients with inflammatory bowel disease support the opportunity of a large-scale trial to validate its use as a screening test.

Adenoma↗
PubMed1994

[Hemoperitoneum supporting difficult diagnosis of diffuse hepatocarcinoma in liver cirrhosis].

The cases of two patients with liver cirrhosis HCV-related, admitted in our Department in consequence of the development of ascites, anemia and clinical deterioration, are reported. Both patients had all major risk factors for hepatocellular carcinoma and anamnestic and physical findings suggesting this diagnosis; nevertheless, the alpha-1-fetoprotein serum levels and the ultrasonographic findings were not diagnostic for primary hepatic neoplasm. Explorative paracentesis was diagnostic, demonstrating the presence of hemoperitoneum (the hematocrit ratio in the ascitic fluid was 12 and 10, respectively). Magnetic resonance revealed extensive diffuse hepatocellular carcinoma on both cases. Hemoperitoneum, in patients with liver cirrhosis, in face of non diagnostic levels of alpha-1-fetoprotein and ultrasonographic findings, can be indicative of the spontaneous rupture of a diffuse type of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1994

High D-dimer levels: a possible index of risk of overt disseminated intravascular coagulation and/or digestive bleeding in advanced liver cirrhosis?

The coagulation parameters of fourteen patients with advanced liver cirrhosis (3 in Child class B and 11 in class C) were prospectively determined quarterly for one year in order to evaluate the possible relationship between high D-dimer levels and incidence of disseminated intravascular coagulation (DIC) and of gastrointestinal bleeding. The values of D-dimer, fibrin(ogen) degradation products, platelets, fibrinogen, prothrombin activity and antithrombin III were fairly stable in almost all patients and no patient developed an overt DIC; one patient had a significant increase in D-dimer three months after the first control. During the one year follow-up, four patients died, one by the occurrence of hepatocellular carcinoma and three by digestive bleeding. Overall, four patients had upper digestive tract bleeding, three from esophageal varices and one from hemorrhagic gastritis. Hemorrhage was more frequent in patients with high D-dimer levels (3/7, 43%) than in patients with normal D-dimer levels (1/7, 14%). In conclusion, the detection of high D-dimer levels in patients with advanced cirrhosis is not predictive for the occurrence of a overt DIC but seems to be related with an increased risk of gastrointestinal bleeding.

Aged↗
PubMed1993

Duplex Doppler ultrasonographic comparison of the effects of propranolol and isosorbide-5-mononitrate on portal hemodynamics.

Eighteen cirrhotic patients with esophageal varices at risk for bleeding took part in a double-blind study. The variations in PFV induced by either 40 mg of propranolol or 60 mg of sustained-release isosorbide-5-mononitrate on two consecutive days were evaluated with a duplex Doppler device. Both drugs caused a significant decrease in maximum (propranolol, P = 0.002; isosorbide-5-mononitrate, P = 0.021). Four patients responded to propranolol, three to isosorbide-5-mononitrate, and eight to both drugs; three did not show any change. Duplex Doppler sonography may be of use in the selection of the right pharmacologic treatment for the individual patient for the prevention of a bleeding esophageal varix.

Delayed-Action Preparations↗
PubMed1993

[The activity of misoprostol on the gastric and duodenal mucosal damage in patients with liver cirrhosis].

Twenty-five liver cirrhosis patients with endoscopically demonstrated gastro-duodenal mucosal damage (microhemorrhages, erosions, ulcers) were treated with misoprostol (prostaglandin E1) 400 mg/die. Eleven patients (44%) had abdominal pain and diarrhea and stopped treatment. Three months later, a new endoscopy was performed in the 11 patients that completed the study (3 patients were lost at follow up). Mucosal damage was stable in 5 patients (45%) and improved in 6 patients (55%), with complete absence of mucosal lesions in 2 patients (P = 0.027, Wilcoxon Ranks test). No case of worsening was observed and no patient had digestive bleeding during treatment. Digestive bleeding is a common complication of liver cirrhosis, originating in about 50% of cases from gastro-duodenal mucosal damage. Misoprostol suggests itself as a possible alternative therapy to the drugs usually utilized in these lesions (beta-blockers, H2-inhibitors), but individual intolerance is frequent and must be preliminary excluded.

Aged↗
PubMed1992

[Two patients with liver cirrhosis who presented with alpha-fetoprotein values diagnostic of hepatocarcinoma but without evidence of neoplasms].

Two liver cirrhosis (LC) patients with all major risk factors for hepatocellular carcinoma (HCC) had, at presentation, serum alfa-fetoprotein levels (AFP) higher than 500 ng/ml, usually considered diagnostic for HCC. They had elevated serum ALT levels too. No neoplastic liver lesions were detected by imaging techniques in both cases. During the following three months we noted a progressive improvement of clinical conditions with contextual normalization of AFP and ALT values. Therefore we suggest, when AFP is strongly elevated in LC patients but no hepatic lesion is detectable, a check for AFP and ALT time-course, before diagnosis HCC.

Biomarkers, Tumor↗