Assessment of intrafamilial clinical variability of poikiloderma with neutropenia by a 10-year follow-up of three affected siblings

Clericuzio-type poikiloderma with neutropenia is a well-defined nosological entity, but despite a remarkable number of clinical reports, no long term follow-up data has been presented to date regarding patients with this rare condition.Here we describe the results of clinical follow-up of three siblings, one male (Patient 1) and two females (Patients 2 and 3), subsequent to their first clinical and then molecular diagnosis of Clericuzio-type poikiloderma with neutropenia syndrome due to mutation of USB1gene. Patient 1 always expressed the most severe phenotype, while patients 2 and 3 showed an intermediate and mild phenotype, respectively, as observed since their first clinical evaluation. None of the patients developed skin cancer and/or myelodysplastic disorders considering the peripheral haematological findings. Lens opacity, never reported before, was found in two of the three patients.The long term follow-up observations confirm the stability over time of the pronounced intra-familial heterogeneity of clinical manifestations observed prior to and upon molecular diagnosis. We conclude that prolonged follow-up is an adjunct tool to monitor intra-familial variability of PN clinical spectrum which may favour surveillance of more serious complications of the disease among siblings, when a patient-specific clinical expressivity is present.     

Factors predicting radiation pneumonitis in lung cancer patients: a retrospective study.

PURPOSE: To evaluate clinical and lung dose-volume histogram based factors as predictors of radiation pneumonitis (RP) in lung cancer patients (PTs) treated with thoracic irradiation. METHODS AND MATERIALS: Records of all lung cancer PTs irradiated at our Institution between 1994 and 2000 were retrospectively reviewed. Eighty-four PTs with small or non-small-cell lung cancer, irradiated at >40 Gy, with full 3D dosimetry data and a follow-up time of >6 months from start of treatment, were analysed for RP. Pneumonitis was scored on the basis of SWOG toxicity criteria and was considered a complication when grade> or =II. The following clinical parameters were considered: gender, age, surgery, chemotherapy agents, presence of chronic obstructive pulmonary disease (COPD), performance status. Dosimetric factors including prescribed dose (Diso), presence of final conformal boost, mean lung dose (Dmean), % of lung receiving > or =20, 25, 30, 35, 40, and 45 Gy (respectively V20-->V45), and normal tissue complication probability (NTCP) values were analysed. DVHs data and NTCP values were collected for both lungs considered as a paired organ. Median and quartile values were taken as cut-off for statistical analysis. Factors that influenced RP were assessed by univariate (log-rank) and multivariate analyses (Cox hazard model). RESULTS: There were 14 PTs (16.6%) who had > or =grade II pulmonary toxicity. In the entire population, the univariate analysis revealed that many dosimetric parameters (Diso, V20, V30, V40, V45) were significantly associated with RP. No significant correlation was found between the incidence of RP and Dmean or NTCP values. Multivariate analysis revealed that the use of mitomycin (MMC) (P=0.005) and the presence of COPD (P=0.026) were the most important risk factor for RP. In the group without COPD (55 PTs, seven RP) a few dosimetric factors (Dmean, V20, V45) and NTCP values (all models) were associated with RP in the univariate analysis (P< or =0.06). According to the multivariate analysis, the use of MMC was independently associated with RP (P=0.007), while Dmean approached statistical significance (P=0.082). CONCLUSIONS: In this study the use of mitomycin or the presence of COPD is associated with a higher risk of RP. In the entire population NTCP values were not significantly correlated with the incidence of RP. Mean lung dose shows a clear trend toward statistical significance in the patient group without COPD.     

A 2-year pilot trial of continuous subcutaneous insulin infusion versus intensive insulin therapy in patients with newly diagnosed type 1 diabetes (IMDIAB 8)

In a pilot study, the metabolic effects of continuous subcutaneous insulin infusion (CSII) versus intensive subcutaneous insulin therapy (ISIT) started at diagnosis in patients with Type 1 diabetes and continued for a 2-year period were evaluated and compared. Twenty-three patients (between 12 and 35 years old, mean +/- SD 18.4 +/- 9 years) were randomized into two treatment groups (CSII vs. ISIT), and both received supplemental nicotinamide (NA), 25 mg/kg of body weight. CSII was started immediately after admission to the hospital. Parameters of metabolic control [insulin dose, hemoglobin A1c (HbA1c), and C-peptide] were evaluated for a 2-year follow-up period. Data are presented for a total of 19 patients who remained in the study for its duration. Two years after diagnosis, mean +/- SD HbA1c was 6.3 +/- 0.5% and 6.2 +/- 0.3% for the CSII and ISIT groups, respectively (p=not significant). Compared with baseline values, an increase of baseline C-peptide of 38% for the CSII group and 27% for the ISIT group was observed; however, the difference between the groups was not significant. The insulin requirement for the entire duration of the study, but not at entry and 3 months, was significantly higher in CSII compared with ISIT patients (0.62 +/- 0.4 IU/kg/day vs. 0.3 +/- 0.4 IU/kg/day, respectively; p<0.01). After trial completion patients on CSII continued with this mode of therapy. Implementation of CSII as well as ISIT at diagnosis of Type 1 diabetes and continuation for 2 years thereafter achieved similar and optimal metabolic control, but more insulin was required with the CSII group. Both types of intensive insulin therapy combined with NA are able to preserve C-peptide secretion or even increase baseline levels for up to 2 years after diagnosis.     

Psoriatic arthritis and depressive symptoms: does systemic inflammation play a role?

Clinical Rheumatology - Depression is commonly associated with psoriatic arthritis (PsA), but its risk factors in these patients are largely unrecognized. Pro-inflammatory cytokines involved in the...     

The treatment of carotid artery bifurcation stenoses with systematic stenting: experience of first 100 consecutive cardiological procedures

Carotid endarterectomy still represents the gold standard treatment of carotid artery bifurcation stenosis but percutaneous angioplasty with stenting is rapidly growing as a non-invasive alternative. In this paper we report the results of systematic application of carotid stenting performed in a cardiological setting, particularly as regards clinical management of patients and technical approach. One-hundred (100) procedures of carotid artery stenting (CAS) on 94 consecutive patients, both symptomatic and asymptomatic, with a carotid stenosis > 70%, were performed over a period of 30 months. The technical approach was directly derived from coronary angioplasty with use of large lumen guiding catheters, 0.014 in. intravascular guidewires and distal protection devices usually employed in coronary interventions. In 3 cases, a post-carotid endarterectomy restenosis and in 97 cases, a de-novo lesion, were treated respectively; in 71 cases, the degree of stenosis was 71-89% and in 29 cases, 90-99%. Cerebral protection was obtained with a distal to the lesion endovascular filter in 63 cases. Immediate technical success, i.e. residual stenosis of the treated vessel < 30% and no significant pathologic acceleration of blood flow (< 1.5 m/sec) at the Doppler ultrasound evaluation, was achieved in all procedures (100%). Ninety-six (96) procedures were totally uncomplicated; in-hospital cerebral complications were 1 TIA, 2 minor and 1 major strokes; at 30-day follow-up one additional major stroke occurred. Despite a particularly high incidence of comorbidities, neither unfavorable cardiological complications nor neurologic deaths were reported. Systematic CAS is a feasible treatment of the carotid artery bifurcation stenosis with high procedural success and low perioperative and short term complications. Its performance in a cardiological setting can combine satisfying procedural results and potentially successful handling of cardiovascular complications.     

Morgana acts as a proto‐oncogene through inhibition of a ROCK–PTEN pathway

Morgana/CHP‐1 is a ubiquitously expressed protein able to inhibit ROCK II kinase activity. We have previously demonstrated that morgana haploinsufficiency leads to multiple centrosomes, genomic instability, and higher susceptibility to tumour development. While a large fraction of human cancers has shown morgana down‐regulation, a small subset of tumours was shown to express high morgana levels. Here we demonstrate that high morgana expression in different breast cancer subtypes correlates with high tumour grade, mitosis number, and lymph node positivity. Moreover, morgana overexpression induces transformation in NIH‐3T3 cells and strongly protects them from various apoptotic stimuli. From a mechanistic point of view, we demonstrate that morgana causes PTEN destabilization, by inhibiting ROCK activity, hence triggering the PI3K/AKT survival pathway. In turn, morgana down‐regulation in breast cancer cells that express high morgana levels increases PTEN expression and leads to sensitization of cells to chemotherapy. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd     

Modern drug delivery strategies applied to natural active compounds

Introduction: Colloidal drug delivery systems (CDDSs) are innovative carriers that have been studied in pharmaceutical field from many years to overcome unfavorable physical and chemical features of synthetic drugs. Recently the use of CDDS as carriers for phytochemicals has seen an exponential increase which, in some cases, has led to the rediscovery of ancient and forgotten natural molecules.

Area covered: This article focuses on the main features of CDDS, particularly micro- and nanoemulsions, vesicular carriers and micro- and nanoparticles, loaded with natural active compounds. A detailed review of the literature is presented, introducing the importance of these systems in terms of their capability to optimize the stability of phytochemicals, their absorption through biological membranes and their bioavailability.

Expert opinion: The delivery of phytochemicals is problematic due to poor solubility, poor permeability, low bioavailability, instability in biological milieu and extensive first-pass metabolism. Global research efforts investigating nanotechnology have attempted to overcome these limitations rediscovering and, in some cases, ‘discovering ex novo’ unexpected virtues and benefits associated to these compounds. The ‘nanotechnological approach’ can definitely enhance the pharmacokinetics and therapeutic index of natural active compounds and improve their performance in therapy.     

Evaluation of the Cyclic Fatigue of Two Single Files at Body and Room Temperature with Different Radii of Curvature

Background: To compare the influence of different temperatures and curvature radii on the cyclic fatigue resistance of F6 SkyTaper (F6ST) and One Curve (OC) single file nickel-titanium rotary instruments. Methods: A total of 120 instruments of F6ST and OC #25.06 were evaluated in 5 mm and 3 mm curvature radii at two temperatures (20 °C ± 1 °C and 37 °C ± 1 °C) in 16 mm stainless steel artificial canals associated with a curvature of 60°. The cyclic fatigue of tested files was assessed by employing a customized testing apparatus and expressed as times to fracture (TtF). A statistical analysis was performed with the significance level set at 95%. Results: All instruments decreased their TtF at 37 °C except for OC in the 3 mm radius, in which no significant difference was detected between 20 °C and 37 °C. A 3 mm curvature radius negatively affected TtF of all tested instruments, except for F6ST at 20 °C. F6ST had higher TtF than OC in the 3 mm radius at 20 °C, with no significant difference between them in the other tested conditions. Conclusions: Under the limits of the present in vitro study, body temperature impaired cyclic fatigue resistance of all files, except for OC in the 3 mm curvature radius. All instruments exhibited lower times to fracture in the 3 mm radius, excluding F6ST at 20 °C.