32 research outputs found

    IL CONTROLLO DI QUALITÀ NELL’IMPIEGO DELLA PCR APPLICATA ALLA DETERMINAZIONE QUALITATIVA DELL’HCV-RNA.

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    Detection of hepatitis C virus (HCV) RNA in samples of plasma/serum has become an essential part of the diagnosis and management of HCV-infected patients. Qualitative HCV-RNA tests are used to identify acute HCV infections as well as chronic HCV carriers.In recent years,a variety of commercial and non commercial test systems have been developed for this purpose. Each of these methods is calibrate with proprietary standards and exhibits its own sensitivity (detection limit) and specificity. Obviously, laboratories performing HCV-RNA test should report accurate and reliable results regardless of the type of assay used.Where commercial kit are used for part of or the complete analytical procedure, documented validation points already covered by the kit manufacturer can substitute for the validation by the user.Nevertheless, the performance of the kit with respect to its intended use has to be demonstrated by the user. One of the best ways to assess the performance of individual laboratories for validation of qualitative HCV-RNA test is determine: 1. Specificity. In order to validate the specificity of the analytical procedure, at least 100 HCV-RNA-negative plasma pools should be tested and shown to be non-reactive. 2. Positive cut-off point (detection limit/sensitivity).The positive cut-off point (as defined in the Ph Eur General Method 2. 6. 21) is the minimum number of the target sequences per volume sample which can be detected in 95% of test runs.A dilution series of a working reagent or reference material, which has been calibrated against the WHO HCV International Standard (96/790), should be tested on different days to examine variation between test runs.At least 3 independent dilution series should be tested with a sufficient number of replicates at each dilution to give a total number of 24 test results for each dilution to enable a statistical analysis of the results; 3. Robustness.To demonstrate robustness, at least 20 HCV-RNA negative plasma pools (selected at random) and spiked with HCV-RNA to a final concentration of 3 times the previously determined 95% cut-off value should be tested and found positive; 4. Cross-contamination error.Cross-contamination prevention should be demonstrated by the accurate detection of a panel of at least 20 samples consisting of alternate samples of negative plasma pools and negative plasma pools spiked with high concentrations of HCV (at least 102 x the 95% cut-off value or at least 104 IU/ml)

    RAB39B-mediated trafficking of the GluA2-AMPAR subunit controls dendritic spine maturation and intellectual disability-related behaviour

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    Mutations in the RAB39B gene cause X-linked intellectual disability (XLID), comorbid with autism spectrum disorders or early Parkinson’s disease. One of the functions of the neuronal small GTPase RAB39B is to drive GluA2/GluA3 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) maturation and trafficking, determining AMPAR subunit composition at glutamatergic postsynaptic neuronal terminals. Taking advantage of the Rab39b knockout murine model, we show that a lack of RAB39B affects neuronal dendritic spine refinement, prompting a more Ca2+-permeable and excitable synaptic network, which correlates with an immature spine arrangement and behavioural and cognitive alterations in adult mice. The persistence of immature circuits is triggered by increased hypermobility of the spine, which is restored by the Ca2+-permeable AMPAR antagonist NASPM. Together, these data confirm that RAB39B controls AMPAR trafficking, which in turn plays a pivotal role in neuronal dendritic spine remodelling and that targeting Ca2+-permeable AMPARs may highlight future pharmaceutical interventions for RAB39B-associated disease conditions

    Occult colon cancer in a patient with an unexplained episode of pulmonary embolism

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    The association between venous thromboembolism and cancer has been widely documented and the main factor responsible for cancer-induced venous thromboembolism is considered mostly linked to a hypercoagulation state induced by the cancer itself. There is no consensus on investigative strategies for occult cancer in a patient with a thrombophilic condition. We report a patient who manifested an isolated episode of pulmonary embolism without specific evident sources of venous thromboembolism. The routine clinical and laboratory work-up to detect an occult cancer did not reveal any malignancy. A history of duodenal ulcer in association with a recent slight alteration in bowel habits led us to perform an esophagogastroduodenoscopy which was negative for malignancy, and a barium enema followed by colonoscopy, which revealed the presence of a tumor limited to the large intestine. An unexplained clinically evident hypercoagulation state, even in the presence of mild clinical symptoms, needs more thorough diagnostic strategies when simple methods of screening for occult cancer are negative

    Serum Total Tryptase Level Confirms Itself as a More Reliable Marker of Mast Cells Burden in Mast Cell Leukaemia (Aleukaemic Variant)

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    Mast cell leukemia (MCL) is a very rare form of systemic mastocytosis (SM) with a short median survival of 6 months. We describe a case of a 65-year-old woman with aleukaemic variant of MCL with a very high serum total tryptase level of 2255 μg/L at diagnosis, which occurred following an episode of hypotensive shock. She fulfilled the diagnostic criteria of SM, with a bone marrow smear infiltration of 50–60% of atypical mast cells (MCs). She tested negative for the KIT D816V mutation, without any sign of organ damage (no B- or C-findings) and only few mediator-related symptoms. She was treated with antihistamine alone and then with imatinib for the appearance of anemia. She maintained stable tryptase level and a very indolent clinical course for twenty-two months; then, she suddenly progressed to acute MCL with a serum tryptase level up to 12960 μg/L. The patient died due to haemorrhagic diathesis twenty-four months after diagnosis. This clinical case maybe represents an example of the chronic form of mast cell leukemia, described as unpredictable disease, in which the serum total tryptase level has confirmed itself as a reliable marker of mast cells burden regardless of the presence of other signs or symptoms

    Il Centro e l’Associazione Italiana di Cultura Classica

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    Descrizione delle molteplici attività del Centro di Studi Papirologici e dell'Associaione Italiana di Cultura Classica
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