A HIND III RFLP AND A GENE LESION IN THE COAGULATION FACTOR-VIII GENE

The presence and inheritance of restriction fragment length polymorphisms (RFLPs) and gene lesions in the coagulation factor VIII gene were investigated in 15 hemophilia families. An abnormal HindIII 2.6-kb band, previously detected in a severe hemophiliac, was observed in a not severely affected patient and also in the normal gene of a woman carrying a hemophilic gene in which the lesions was found. The TaqI site in exon 24 of this defective gene was removed by a C to T transition causing an amino acid change (Arg----Gln). Very low amounts of factor VIII activity and antigen were detected in the severely affected grandson. The presence of the HindIII 2.6-kb fragment in both normal and pathological genes indicates that a factor VIII RFLP without functional meaning was found. Its frequency, determined in 60 chromosomes, is 0.18. Double digestions enabled us to map the polymorphic site 3' to the exon 19

SOCIAL REPRESENTATIONS OF HAEMOPHILIA IN ADOLESCENTS AND YOUNG ADULTS: A PSYCHOSOCIAL PERPECTIVE ON COMPLIANCE

Background. This paper is intended as an exploration of the Social Representations of haemophilia, and the normalization process in adolescents and young adults affected by congenital hemorrhagic diseases. An extensive medical literature (Petrini & Seuser, 2009) regarding adolescents with chronic illness shows that during adolescence there is an abandonment of treatment regimens and reduced adherence to medical prescriptions. The purpose of the research was to understand the phenomenon reported in the scientific literature of the reduction of compliance in adolescence in regard to the social representation of haemophilia. In our hypothesis, such representations highlight how haemophilia is included in the process of construction of the Self, specifically referring to the increasing autonomy from the family and the socialization with peers. Materials and methods. The research involved 20 adolescents and young adults suffering from congenital hemorrhagic diseases. We administered semi-structured interview to all the participants. The interviews were analyzed using the Thematic Analysis of Elementary Context from T-Lab software (Lancia, 2004), with the aim of exploring the lexical worlds (Reinert, 1995). Results and Conclusions. The results suggest different themes that organize the affective and cognitive signification process of haemophilia. The recourse to a therapeutic regime like prophylaxis looks like more associated to an integration of the illness in the Self and in the daily life, while the therapy on demand is more associated to a representation of the haemophilia as external to the Self and concerning only the body. Furthermore, different ranges of age are linked to different kinds of representation: haemophilia is considered by the adolescents like a body's break, while it is considered by young adults as a mystery for which researching causes in the family history

Growing up with a chronic disease: identity, autonomy and compliance in adolescents and young adults affected by hemophilia

Introduction: An extensive medical literature (Petrini & Seuser, 2009) regarding adolescents with chronic illness shows that during adolescence there is an abandonment of treatment regimens and a reduced adherence to medical prescriptions. The aim of the research was to understand the phenomenon of the reduction of compliance in adolescents and young adults with chronic illness, particularly hemophilia, in regard to the representations of illness, the identity and the normalization processes. Methods: The research involved 20 adolescents and young adults suffering from a chronic hemorrhagic illness and 15 adolescents and young adults affected by diabetes. We administered semi-structured interview to all the participants. The interviews were analyzed using the Thematic Analysis of Elementary Context from T-Lab software (Lancia, 2004, Reinert, 1995). Results: In our hypothesis, from a psychosocial point of view, the reduction of compliance is related to different representations of the illness and such representations highlight how hemophilia is included in the process of construction of the Self, specifically referring to the increasing autonomy from the family and the socialization with peers. Discussion/Conclusion: The results suggest different themes that organize the affective and cognitive representations of both chronic diseases. In respect to haemophilia, the recourse to a therapeutic regime like prophylaxis looks like more associated to an integration of the illness in the Self and in the daily life, while the therapy on demand is more associated to a representation of the Hemophilia as external to the Self and concerning only the body. Furthermore, different ranges of age are linked to different kinds of representation: Hemophilia is considered by the adolescents like a body\u2019s break, while it is considered by young adults as a mystery for which researching causes in the family history. In respect to diabetes, the analysis are still in progress

Persistent B19 parvovirus infections in hemophilic HIV?1 infected patients

B19 infection can be acquired by transmission with blood factors in patients with congenital bleeding disorders, requiring clotting factor concentrates. In immunodeficient patients, the failure of immunity to clear B19 virus may produce persistent infections. The presence of B19 DNA in blood samples from seven haemophilic patients with concomitant HIV-1 infection was studied over a period of three-to-four years. Dot blot hybridization assays with DNA and RNA probes were used to detect medium high viremias, and polymerase chain reaction (PCR) to detect very low viremic titres. Three patients were negative for B19 DNA in all the blood samples, while four patients were persistently positive for B19 DNA. Viral persistence, which in one patient was detected throughout the study period (40 months), occurred at low titre in all four positive patients with some recurrent increases in viral titre. In the four patients persistently positive for B19 DNA, acute or chronic clinical symptoms and signs that could be associated with B19 were not noted when virus was present at low titre (B19 DNA detectable only by PCR). When patients had a higher viral titre (B19 DNA detectable by dot blot hybridization) acute manifestations (aplastic crisis, Fifth disease, fevers, pneumonitis) were found

The Wells rule and D-dimer for the diagnosis of isolated distal deep vein thrombosis

Background: Pretest clinical probability with the Wells rule and D-dimer have been widely investigated for the diagnosis of symptomatic proximal deep vein thrombosis (DVT) of the lower limbs, but they have not been formally tested for symptomatic isolated distal DVT diagnosis. Objective: To evaluate the diagnostic accuracy of the Wells rule and D-dimer for isolated distal DVT. Design, Setting, and Patients: This was a single-center, cross-sectional study including 873 consecutive outpatients with suspected DVT, in whom pretest clinical probability determination, D-dimer determination (STA Liatest; cut-off of <500ngmL -1) and complete compression ultrasonography of both lower limbs were performed. Results: The isolated distal DVT prevalence was 12.4% (90/725). The sensitivity of the Wells rule for isolated distal DVT was 47% (95% confidence interval [CI] 36-57%), the specificity was 74% (95% CI 70-77%), and the negative and positive predictive values were 91% (95% CI 88-93%) and 20% (95% CI 15-26%), respectively. Patients with isolated distal DVT had higher D-dimer levels than patients without DVT (1759±1576 vs. 862±1079ngmL -1, P=0.0001). D-dimer was negative in 13 patients with isolated distal DVT. D-dimer sensitivity and specificity for isolated distal DVT were 84% (95% CI 75-91%) and 50% (95% CI 46-54%), respectively, with a negative predictive value of 96% (95% CI 93-98%). In patients with low pretest clinical probability, the D-dimer negative predictive value was 99% (95% CI 95-100%). Conclusion: In clinically suspected DVT with negative proximal compression ultrasonography, pretest clinical probability with the Wells rule has a low diagnostic accuracy for isolated distal DVT. D-dimer has a better negative predictive value, but alone it does not exclude isolated distal DVT. In patients with low pretest clinical probability, D-dimer had a negative predictive value of >95% for isolated distal DVT.not availabl

Residual factor VII activity and different hemorrhagic phenotypes in CRM+ factor VII deficiencies (Gly331Ser and Gly283Ser)

Two cross-reacting material-positive (CRM(+)) factor VII (FVII) mutations, associated with similar reductions in coagulant activity (2.5%) but with mild to asymptomatic (Gly331Ser, c184 [in chymotrypsin numbering]) or severe (Gly283Ser, c140) hemorrhagic phenotypes, were investigated. The affected glycines belong to structurally conserved regions in the c184 through c193 and c140s activation domain loops, respectively. The natural mutants 331Ser-FVII and 283Ser-FVII were expressed, and in addition 331Ala-FVII and 283Ala-FVII were expressed because 3 functional serine-proteases bear alanine at these positions. The 331Ser-FVII, present in several asymptomatic subjects, showed detectable factor Xa generation activity in patient plasma (0.7% +/- 0.2%) and in reconstituted system with the recombinant molecules (2.7% +/- 1.1%). The reduced activity of recombinant 283Ala-FVII (7.2% +/- 2.2%) indicates that the full function of FVII requires glycine at this position, and the undetectable activity of 283Ser-FVII suggests that the oxydrile group of Ser283 participates in causing severe CRM(+) deficiency. Furthermore, in a plasma system with limiting thromboplastin concentration, 283Ser-FVII inhibited wild-type FVIIa activity in a dose-dependent manner

Whole-Arm Ultrasound to Rule Out Suspected Upper-Extremity Deep Venous Thrombosis in Outpatients

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