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Biomedical subjects

G Mancuso

Publications and source records attributed to G Mancuso.

At least 19 recordsLinked to original sources
PubMed2006

A prospective randomized trial of high and standard dosages of recombinant factor VIIa for treatment of hemarthroses in hemophiliacs with inhibitors.

AIM: A multicenter randomized open-label crossover prospective trial was designed to compare the efficacy, safety, and cost of standard and high dosages of recombinant factor VIIa (rFVIIa) for home treatment of hemarthroses in hemophiliacs with inhibitors. METHODS: Patients were instructed to treat, within 6 h from the onset of bleeding, four consecutive hemarthroses of ankles, knees, or elbows, either with the rFVIIa standard dose of 90 microg kg(-1) (repeated as necessary every 3 h) or with a single high dose of 270 microg kg(-1). Patients who did not achieve a clinical success within 9 h continued rFVIIa treatment with repeated standard doses. Response to treatment was assessed for up to 48 h by patients/caregivers, who reported on a Visual Analogue Scale (VAS) graded from 0 to 100 the improvement in symptoms and also rated the responses as effective, partially effective or ineffective. Success was defined a treatment course rated as effective and with a VAS score > or =70 and failure a treatment course rated as ineffective and VAS score < or =30, whereas treatment courses that did not fulfill these criteria were considered partial responses. RESULTS: Twenty hemophiliacs with inhibitors were originally enrolled (median age: 27 years), 18 of them treated 32 hemarthroses assigned to the standard-dosage and 36 to the high-dosage regimen, during the study period of 18 months. Forty-eight hemarthroses (71%) occurred in target joints. Success rates for standard- and high-dosage regimens were similar: 31% and 25% at 9 h, 53% and 50% at 24 h, 66% and 64% at 48 h, the end point for outcome assessment. The median number of rFVIIa infusions needed to achieve a successful course was significantly greater for the standard-dosage (n = 3) than for the high-dosage regimen (n = 1), and the median amount of rFVIIa ultimately used per successful course was identical (270 microg kg(-1)). CONCLUSION: Our results indicate that a high-dosage regimen with rFVIIa for home treatment of hemarthroses is effective, safe, does not imply an increased consumption of rFVIIa and requires the infusion of a smaller number of rFVIIa doses. Its convenience is particularly relevant in cases with difficult venous access and in hemorrhages into target joints.

Adolescent↗
PubMed2005

Simultaneous occurrence of dysaesthetic peno/scroto-dynia and stomatodynia.

The 'dynias' are a group of chronic focal pain syndromes with a predilection for orocervical or urogenital regions. Only exceptionally do they involve both sites in the same patient. Here, we report a case of simultaneous occurrence of dysaesthetic peno/scroto dynia and stomatodynia.

Burning Mouth Syndrome↗
PubMed2002

Clinical efficacy of highly purified, doubly virus-inactivated factor VIII/von Willebrand factor concentrate (Fanhdi) in the treatment of von Willebrand disease: a retrospective clinical study.

The goal of therapy in patients with von Willebrand disease (vWD) is to correct the dual defect of primary haemostasis and intrinsic coagulation reflected by low levels of von Willebrand factor (vWF) and factor VIII coagulant activity (FVIII:C). Factor VIII/von Willebrand factor (FVIII/vWF) concentrates are currently the treatment of choice in vWD patients unresponsive to desmopressin (DDAVP). However, only few studies on their clinical use are available so far. The main objective of this study was to retrospectively evaluate the clinical efficacy of a highly purified, doubly virus-inactivated FVIII/vWF concentrate with a high content of FVIII/vWF (Fanhdi). Twenty-two patients with congenital vWD have been treated from 1999 to 2001 at eight specialized centres belonging to the Italian Association of Hemophilia Centers (AICE). Ten males and 12 females, median age 28.5 years, range 5-70 years) had type 3 vWD (six cases), DDAVP-unresponsive type 1 (nine cases) and type 2B (seven cases). The study drug was given to stop or prevent 12 bleeding episodes or to prevent excessive bleeding during 14 surgical or invasive procedures. Overall, replacement therapy with the concentrate showed an excellent to good clinical efficacy in 92% of bleeding episodes and in 93% of surgical procedures. No adverse events occurred during 1,601 infusions, accounting for a total of 304,500 IU of FVIII:C administered. These results confirm the efficacy and safety of this concentrate in the management of bleeding episodes and in the prevention of excessive bleeding during major and minor surgery.

Adolescent↗
PubMed2001

Cigarette smoking and attention: processing speed or specific effects?

RATIONALE: It has been evidenced that nicotine acts on some dimensions of human attention. OBJECTIVE: This study was carried out to test whether the positive effects of nicotine usually observed on the posterior system are specific or should rather be explained in terms of an effect of nicotine on eye movement velocity. METHODS: Ten participants were submitted to four tasks assessing attention. The tasks were borrowed from Zimmermann and Fimm's Battery for the Assessment of Attention: alert, eye movements, visual search and incompatibility. The order of the different tasks was balanced among participants. A within-subjects repeated-measure design was used. Participants received a 0.9-mg or 0.1-mg nicotine cigarette. The 0.1-mg cigarette was used as control. The order of administration of doses over sessions was counterbalanced. During the testing day, volunteers smoked their own cigarette and then waited 3 h without smoking. At the end of this abstinence period, participants completed the baseline tests before smoking an experimental cigarette ad libitum. They were then tested again. RESULTS: Participants who received nicotine appeared to respond faster in an eye movement task--a task associated with a non-elaborated attentional process. Similarly, their alert state improved. On the contrary, no effect of nicotine was observed in the incompatibility task and in the visual search task depending on elaborated attentional process. CONCLUSIONS: Data support previous observations and suggest that, first, non-elaborated information processing appeared to be more sensitive to nicotine and, second, this effect is not due to a velocity factor.

Adult↗
PubMed2001

Eosinophilic pustular eruption associated with transdermal fentanyl.

A 70-year-old man developed a widespread eruption of sterile pustules on normal skin, mainly on the trunk, face and base of the limbs, 2 days after application of a fentanyl-transdermal therapeutic system (fentanyl-TTS) patch. The eruption was not accompanied by fever. The main histopathological finding was an intraepidermal pustule filled almost exclusively with eosinophils. Suspension of the fentanyl-TTS led to rapid and definitive spontaneous regression of the pustules in about 10 days. A similar pustular reaction related temporally to fentanyl-TTS administration had appeared several weeks before the current eruption.

Administration, Cutaneous↗
PubMed2001

Anti-idiotypic vaccination against group B streptococci.

We describe the antigenic properties of an anti-idiotypic single chain fragment variable (scFv) recombinant antibody mimicking the type III capsular polysaccharide of group B streptococci (GBS), an important cause of neonatal sepsis. This scFv could compete with the nominal antigen for binding to specific mouse or rabbit antibodies. Moreover, the scFv elicited, in mice, the production of antibodies which reacted against the type IlI polysaccharide and passively protected neonatal pups from GBS disease. Maternal immunization with the scFv also protected neonatal mice against GBS infection. Next, the scFv was expressed on the surface of the commensal bacterium Streptococcus gordonii. Intravaginal inoculation of mice with these recombinant bacteria induced significant elevations in serum titers of anti-GBS type III antibodies. Therefore, the expression scFv in commensal bacteria may be a convenient and effective way of delivering anti-idiotypic vaccines.

Animals↗
PubMed2000

Beta 2 integrins are involved in cytokine responses to whole Gram-positive bacteria.

Proinflammatory cytokines have an important pathophysiologic role in septic shock. CD14 is involved in cytokine responses to a number of purified bacterial products, including LPS. However, little is known of monocyte receptors involved in cytokine responses to whole bacteria. To identify these receptors, human monocytes were pretreated with different mAbs and TNF-alpha was measured in culture supernatants after stimulation with whole heat-killed bacteria. Human serum and anti-CD14 Abs significantly increased and decreased, respectively, TNF-alpha responses to the Gram-negative Escherichia coli. However, neither treatment influenced responses to any of the Gram-positive bacteria tested, including group A and B streptococci, Listeria monocytogenes, and Staphylococcus aureus. Complement receptor type III (CR3 or CD18/CD11b) Abs prevented TNF-alpha release induced by heat-killed group A or B streptococci. In contrast, the same Abs had no effects when monocytes were stimulated with L. monocytogenes or S. aureus. Using either of the latter bacteria, significant inhibition of TNF-alpha release was produced by Abs to CD11c, one of the subunits of CR4. To confirm these blocking Ab data, IL-6 release was measured in CR3-, CR4-, or CD14-transfected Chinese hamster ovary cells after bacterial stimulation. Accordingly, streptococci triggered moderate IL-6 production (p < 0.05) in CR3 but not CD14 or CR4 transfectants. In contrast, L. monocytogenes and S. aureus induced IL-6 release in CR4 but not CR3 or CD14 transfectants. Collectively our data indicate that beta 2 integrins, such as CR3 and CR4, may be involved in cytokine responses to Gram-positive bacteria. Moreover, CD14 may play a more important role in responses to whole Gram-negative bacteria relative to Gram-positive ones.

Adult↗
PubMed2000

A novel two base pair deletion in the factor V gene associated with severe factor V deficiency.

We studied a family in which the proband, a 13-year-old boy, had unmeasurable plasma levels of coagulation factor V antigen and activity. Clinical symptoms were severe, with several episodes of haemorrhages in the mucosal tracts (gastrointestinal, nose and urinary) and recurrent haemarthroses that caused permanent arthropathy. Sequence analysis of the factor V gene demonstrated the presence of a novel 2 base pair (bp) homozygous deletion in exon 13 at positions 2833-2834. This mutation, present in the heterozygous state in the asymptomatic mother and absent in the healthy brother, introduced a frameshift and a premature stop at codon 900. This would predict the synthesis of a truncated factor V molecule, lacking part of the B domain and the complete light chain. Because of the existence of a surveillance mechanism that selectively recognizes and degrades mRNA molecules carrying premature termination codons, we analysed the relative abundance of mutant vs. wild-type mRNA molecules in the platelets of the heterozygous proband's mother. The mutant mRNA was significantly reduced in amount (mutant/wild-type ratio 0.35). This is the first reported mutation in the factor V gene causing severe factor V deficiency, the effect of which was quantitatively analysed at mRNA level.

Adolescent↗
PubMed2000

Treatment of children with haemophilia in Europe: a survey of 20 centres in 16 countries.

A survey was made of the current status of treatment of haemophilic boys at 20 centres in 16 European countries and includes approximately 1500 of the estimated 6500 haemophiliacs in the participating countries. Many mild haemophiliacs are not seen, or seen infrequently, at haemophilia centres and this requires study. Nine of 18 centres provide continuous prophylaxis to 80-100% of their patients, five centres provide it to 55-80% and the remaining four centres to 15-40% of the boys. The median dose given was 6240 U kg-1 year-1 (range 3120-7800). Four centres administered only recombinant concentrates to children with severe haemophilia A, while seven centres administered recombinant concentrates to 75-90% and the remaining centres to less than 50% of the boys (two centres < 10%). When asked for the choice of concentrate for a newly diagnosed boy with severe haemophilia A, all but one centre preferred recombinant concentrate. Most boys below 6 years received concentrates via a peripheral vein but three centres preferred a central venous line for 80-100% of the boys. Thirteen of 18 centres applied home treatment to 84-100% of the boys and the remaining five centres to 57-77% of the boys.

Adolescent↗
PubMed2000

Chemokine concentrations in nasal washings of infants with rhinovirus illnesses.

We determined RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin-8 (IL-8) concentrations, and total white blood cell (WBC) and differential counts in nasal wash samples from rhinovirus-infected infants presenting with wheezing or acute upper respiratory illness alone and compared them with those from healthy infants. RANTES concentrations were significantly greater in acute samples from wheezy patients than in those from patients with acute upper respiratory illness only, or in control samples. IL-8 concentrations and WBC and neutrophil counts were significantly greater in acute samples from wheezy infants and patients with upper respiratory illness alone than in control samples, but they did not differ significantly between the 2 patient groups.

Chemokine CCL5↗
PubMed2000

Human monocyte receptors involved in tumor necrosis factor responses to group B streptococcal products.

Several group B streptococcal products have been previously found to stimulate human monocytes to produce tumor necrosis factor alpha. In order to identify the receptors involved in these responses, monocytes were stimulated with purified group- or type-specific carbohydrates or lipoteichoic acid in the presence of anti-receptor monoclonal antibodies, soluble CD14, or lipopolysaccharide-binding protein. Results indicate that CD14 plays an important role in tumor necrosis factor alpha responses to all of the stimuli tested. Moreover, both CD14 and complement receptor type 3 may be involved in responses to the group-antigen.

Animals↗
PubMed2000

Identification and three-dimensional structural analysis of nine novel mutations in patients with prothrombin deficiency.

Prothrombin deficiency is an autosomal recessive disorder associated with a moderately severe bleeding tendency. In this study, 13 patients with prothrombin deficiency were screened for the presence of alterations in the prothrombin gene, and nine novel candidate mutations were identified. Of 11 patients with hypoprothrombinemia, ten are homozygous for five mutations and one patient is a compound heterozygote. The two patients with dysprothrombinemia are homozygous for two mutations. Eight of nine mutations are missense ones associated with single amino acid substitutions in the propeptide (Arg-1Gln, Arg-2Trp), the kringle-1 (Asp118Try) and kringle-2 (Arg220Cys) domains and the catalytic serine protease domain (Gly330Ser, Ser354Arg. Arg382His and Arg538Cys). The ninth mutation is an in-frame deletion of 3 bp that results in the omission of one amino acid (del Lys 301/302). The combination of these missense mutations with crystal structures for alpha-thrombin and the prothrombin fragments 1 and 2 resulted in new insight into the function of alpha-thrombin. The hypoprothrombinemia mutations were inferred to affect either the cleavage of the propeptide from the Gla domain, the stability of the kringle-1 and -2 domains, or the close association of the A and B chains of the serine protease domain. The dysprothrombinemia mutations were inferred to directly affect catalytic function through their location at the active site crevice or exosite 1 within the serine protease domain.

Adolescent↗
PubMed1999

Role of IL-10 in a neonatal mouse listeriosis model.

This study was undertaken to test the hypothesis that altered IL-10 production plays a role in the increased susceptibility of neonates to listeriosis. Plasma IL-10 levels were measured in neonatal and adult mice at various times after infection with Listeria monocytogenes. Relative to adults, neonatal mice had markedly increased IL-10 levels early in the course of infection with Listeria using a 90% lethal dose. Higher neonatal IL-10 responses were also observed after injecting adults and pups with equal doses of killed organisms. Splenic macrophages from neonates produced higher IL-10 levels than those of adults after in vitro stimulation with killed bacteria, confirming in vivo observations. Moreover, IL-10 blockade had differential effects in neonates and adults infected with live Listeria. In adult mice, anti-IL-10 Abs decreased bacterial burden early in the course of infection, but were no longer effective at 6 days or later after challenge. In the pups, however, the same treatment had beneficial effects both early and late during infection and resulted in increased survival. Collectively, our data suggest that an overproduction of IL-10 by macrophages may at least partially explain the increased susceptibility of neonates to listeriosis, and provide further evidence that cytokine production is different in adults and neonates.

Aging↗