The Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) 0496 protocol, through the central handling of bone marrow samples at presentation, allowed us to combine cytogenetic and molecular ...information on a large series of adults with acute lymphoblastic leukemia (ALL) treated homogeneously, enabling us to define as broadly as possible their genetic profile and to determine the impact on outcome of the cytogenetic-molecular signature. Of 414 patients centrally processed, 325 were considered for the categorization into the following cytogenetic-molecular subgroups: normal, t(9;22)/BCR-ABL, t(4;11)/MLL-AF4, t(1;19)/E2A-PBX1, 9p/p15-p16 deletions, 6q deletions, miscellaneous structural abnormalities, and hyperdiploid. The inclusion into each subgroup was based on a hierarchical approach: molecular abnormalities with adverse prognosis had precedence over karyotypic changes with less-defined prognosis and the latter over ploidy. Patients without abnormalities and those with isolated 9p/p15-p16 deletions showed a relatively favorable outcome (median disease-free survival DFS, > 3 years). The t(9;22)/BCR-ABL, t(4;11)/MLL-AF4, t(1; 19)/E2A-PBX1 defined a group with dismal prognosis (median DFS, 7 months), whereas 6q deletions, miscellaneous aberrations, and hyperdiploidy predicted an intermediate prognosis (median DFS, 19 months). This study highlights the importance of a combined cytogenetic-molecular profiling of adult ALL at presentation as a critical independent determinant of their outcome, providing further evidence of the necessity of a risk-adapted therapeutic algorithm for an optimal management of these patients.
Karyotypic analysis in adult ALL has provided relevant insights in the prognostic significance of chromosome abnormalities, which in turn become of potential importance for the design of risk-adapted ...therapeutic strategies for newly diagnosed cases. Among structural karyotypic changes, partial deletions of the long arm of chromosome 6 (6q) are reported to be between 4 and 6% of cases of adult ALL by conventional cytogenetics and depict a subset of patients with strict correlation with T-lineage ALL and an unfavorable prognostic likelihood. Recent studies at the molecular level in childhood ALL have shown 6q deletions in up to 30% of the investigated cases. With the aim of more precisely defining the exact incidence of 6q deletions in adult ALL, we started to investigate by interphase FISH patients with normal or failed karyotype included in the GIMEMA 0496 and 2000 protocols. These trials contemplated a central handling of bone marrow samples of the enrolled patients at presentation. We identified the following bacteria-derived artificial chromosome (BAC) clones with a known map location within the most common deleted region of 6q: 90G9 (6q13), 12B13 (6q15), 465M14 (6q21), 81H16 (6q26), 91016 (6q27). BAC clones were obtained from the Children's Hospital Oakland Research Institute (CHORI).
Twenty-seven consecutive ALL patients have so far been analyzed by interphase FISH, 16 with T- and 11 with B-cell phenotype. Eleven cases had a normal karyotype and 16 a failed cytogenetic analysis. Among the cases with normal karyotype, 2 cases with T-cell phenotype showed a deletion in the 6q21 and 6q15 regions, whereas in the group with failed cytogenetics 1 case with B- and 3 cases with T-cell phenotype harbored deletions spanning respectively the 6q13-15 (2), 6q13-q21 and 6q15-21 regions. The median percentage of nuclei with 6q deletion was 30% (range 7–75%). T-ALL deleted cases showed the absence of the most frequent fusion genes detectable with molecular analysis, whereas a BCR-ABL rearrangement was identified in the only B-lineage ALL deleted case. Overall, partial 6q deletions were observed in 22% of the cases analyzed and in 31% of cases with T-cell phenotype. The present study shows that the probe set we have utilized is a useful tool for providing accurate cytogenetic diagnosis of partial 6q deletions and indicates that this abnormality is a frequent karyotypic change in adult ALL, particularly in T-lineage cases where it appears to represent the most relevant genetic anomaly. Since this abnormality is underestimated by conventional cytogenetic analysis, interphase FISH for 6q deletions should be included in the routine genetic screening of the ALL patients with failed or normal cytogenetics
Background: The new version of Diagnostic and Statistical Manual of Mental Disorders (DSM-5th) proposed the Internet Gaming Disorder for the diagnosis of Internet addiction (IA) considering the ...neurobiological evidence of the craving.
Aims: The aim was to test the neural correlate in response to the Internet cue in patients with IA.
Methods: Sixteen males with IA diagnosis (clinical group) and 14 healthy male (control group) were recruited for an experimental visual task composed of Internet images and emotional images. During the visual presentation of Internet cue, electroencefalographic data were recorded using Net Station 4.5.1 with a 256-channels HydroCel Geodesic Sensor Net. Event-related potential (ERP) components and low-resolution electromagnetic tomography (sLoreta) were analysed.
Results: sLoreta analyses showed that patients from the clinical group presented a higher primary somatosensorial cortex and lower paralimbic, temporal and orbito-frontal activation in response to both Internet and emotional images compared to those of the control group.
Conclusions: These results suggest that clinically recognized pathological use of Internet could be linked to dissociative symptoms.
Arterial hypertension is the most prevalent cardiovascular risk factor worldwide. Despite the availability of many and effective antihypertensive medications, the prevalence of uncontrolled blood ...pressure (BP) remains high. As sympathetic hyperactivity has long been recognized as a major contributor to resistant hypertension, catheter-based renal denervation (RDN) has emerged as a new strategy to reduce BP. RDN aims to interrupt the activity of renal sympathetic nerves by applying radiofrequency (RF) energy, ultrasound (US) energy, or injection of alcohol in the perivascular space. The Symplicity HTN-3 trial, the largest sham-controlled trial using the first-generation RF-based RDN device, failed to significantly reduce BP. Since then, new devices and techniques have been developed and consequently many sham-controlled trials using second-generation RF or US-based RDN devices have demonstrated the BP lowering efficacy and safety of the procedure. A multidisciplinary team involving hypertension experts, interventionalists with expertise in renal interventions and anesthesiologists, plays a pivotal role from the selection of the patient candidate for the procedure to the post-procedural care. The aim of this consensus document is to summarize the current evidence about the use of RDN in difficult to treat hypertension and to propose a management strategy from the selection of the patient candidate for the procedure to the post-procedural care.
To measure nitric oxide (NO) concentration in exhaled air of patients with systemic sclerosis (SSc) and to investigate its relationships with lung involvement, complicated or not by pulmonary ...hypertension (PH).
Exhaled NO was measured by chemiluminescence in 47 patients with SSc (16 with PH) and in 30 controls. All the patients underwent Doppler echocardiography to assess pulmonary artery pressure (PAP), lung function tests, and thin section computed tomographic scans of the lung to quantify the extent of fibrosing alveolitis.
Exhaled NO levels were higher in patients with SSc (16.6 +/- 9.1 ppb), particularly those with interstitial lung disease (ILD) (18.3 +/- 10.4 ppb), compared to controls (9.9 +/- 2.9 ppb; p < 0.0001). In patients with PH, exhaled NO was less than in patients without PH (10.7 +/- 5.9 vs 19.6 +/- 9 ppb, respectively; p < 0.001), and patients with PH without ILD had even lower exhaled NO than patients with PH and ILD (6.6 +/- 1.1 vs 12.6 +/- 6.3 ppb; p = 0.004). There was an inverse correlation between PAP and exhaled NO (r = 04).53, p = 0.004). Exhaled NO was not correlated to age, disease duration, current therapy, or form of disease (limited or diffuse).
The increased concentration of exhaled NO in patients with SSc may reflect respiratory tract inflammation. The relatively low value of exhaled NO in patients with PH and the negative correlation between PAP and exhaled NO suggest the important role of NO in regulating pulmonary vascular resistance in patients with SSc.
Platelet-activating factor (PAF), a lipid mediator of inflammation and anaphylaxis, may play a role in several physiopathologic alterations of the lung. A lipid compound with physicochemical and ...biologic characteristics similar to synthetic PAF was extracted and purified from bronchoalveolar lavage (BAL) fluid of 15 of 34 patients with sarcoidosis. PAF was quantitated by a bioassay on washed rabbit platelets. The specificity of platelet aggregation was assessed by using two different PAF receptor antagonists. The incidence of detectable amounts of PAF in BAL fluid of sarcoid patients was statistically significant (chi 2 = 4.064, p = 0.044) when compared with the 14 normal control subjects. The results demonstrated an increased production of PAF in the lower respiratory tract of patients with sarcoidosis. The presence of PAF in BAL fluid, however, did not correlate with radiologic stage, intensity of alveolitis, gallium scanning positivity, angiotensin-converting enzyme serum level, or lung function tests. Therefore, a direct relationship between presence of PAF in BAL fluid and activity of lung disease in patients with sarcoidosis was not directly established.
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