Biologic therapies for plaque type psoriasis in patients with previous malignant cancer: long-term safety in a single- center real-life population.

INTRODUCTION: This is an Italian single-center retrospective study evaluating safety and efficacy of biologic agents in psoriatic patients with a previous diagnosis of malignant cancer. AIM: Management of moderate and severe psoriasis patients with a past medical history of malignancies could be difficult because biologic agents are historically associated with a presumptive increased risk of neoplastic reactivation or of a new incoming cancer. The aim of this study is to assess the safety of biologics in patients with a previous cancer diagnosis. MATERIAL AND METHODS: The study analyzed 16 moderate to severe psoriasis patients with a diagnosis of malignant cancer in the previous 10 years treated with biologic agents for up to at least 96 weeks. In five of these patients, cancer was diagnosed in the previous 5 years. RESULTS: We observed a rapid decrease in PASI (psoriasis area severity index) reaching a 90% improvement in 100% of patients. Oncologic follow up did not show any worsening or reactivation of cancer during the entire observation period. No new malignancies were observed in the analyzed sample. CONCLUSIONS: Biologic agents in our experience have demonstrated to be safe and effective in psoriatic patients with a past medical history of malignant cancer.

Killer immunoglobulin-like receptors (KIR) and their HLA-ligands in Italian paroxysmal nocturnal haemoglobinuria (PNH) patients.

Paroxysmal nocturnal haemoglobinuria (PNH) is a haematopoietic disorder characterized by expansion of phosphatidylinositol glycan-A-defective progenitor(s). Immune-dependent mechanisms, likely involving a deranged T cell-dependent autoimmune response, have been consistently associated with the selection/dominance of PNH precursors. Natural killer (NK) lymphocytes might participate in PNH pathogenesis, but their role is still controversial. NK activity is dependent on the balance between activating and inhibiting signals. Key component in such regulatory network is represented by killer immunoglobulin-like receptors (KIR). KIR are also involved in the regulation of adaptive cytotoxic T cell response and associated with autoimmunity. This study investigated on the frequency of KIR genes and their known human leukocyte antigen (HLA) ligands in 53 PNH Italian patients. We observed increased frequency of genotypes characterized by ≤2 activating KIR as well as by the presence of an inhibitory/activating gene ratio ≥3.5. In addition, an increased matching between KIR-3DL1 and its ligand HLA-Bw4 was found. These genotypes might be associated with lower NK-dependent recognition of stress-related self molecules; this is conceivable with the hypothesis that an increased availability of specific T cell targets, not cleared by NK cells, could be involved in PNH pathogenesis. These data may provide new insights into autoimmune PNH pathogenesis.

[Patients' satisfaction for hospital care among the Italian Regions between 1997 and 2009]. / Soddisfazione dei cittadini per l'assistenza ospedaliera nelle regioni italiane tra il 1997 e il 2009.

Patients have a privileged perspective on health care quality, thus it is important to obtain from them judgments about offered services. Currently, there are no well developed quality monitoring systems related to the patient's perspective, though Istat data sources would b helpful on this issues. We performed a descriptive analysis relating to the satisfaction degree of Italian population for hospital admissions between 1997and 2009. Data were taken from the Istat Multipurpose analysis on some aspect of daylife. Our results show a positive appraisal for medical and nursing assistance; however the rating for the quality of food is lower Our analysis would give a contribution to the appraisal of an outstanding dimension of patients' appraisal of quality of care among the Regions, by considering the implementation of devolution in healthcare since 2001.

Calibration of Elekta aSi EPIDs used as transit dosimeter.

The transit in vivo dosimetry performed by the Electronic Portal Imaging Device (EPID), avoids the problem of solid-state detector positioning on the patient. Moreover, the dosimetric characterization of the recent Elekta aSi EPIDs in terms of signal stability and linearity enables these detectors adaptable for the transit in vivo dosimetry with 6, 10 and 15 MV photon beams. However, the implementation of the EPID transit dosimetry requires several measurements. Recently, the present authors have developed an in vivo dosimetry method for the 3D CRT based on correlation functions defined by the ratios between the transit signal, s(t) (w,L), by the EPID and the phantom mid-plane dose, D(m)(w,L), at the Source to Axis Distance (SAD) as a function of the phantom thickness, w, and the square field dimensions, L. When the phantom mid-plane was positioned at distance d from the SAD, the ratios st(w,L)/s't(d,w,L), were used to take into account the variation of the scattered photon contributions on the EPID as a function of, d and L. The aim of this paper was the implementation of a procedure that uses generalized correlation functions obtained by nine Elekta Precise linac beams. The procedure can be used by other Elekta Precise linacs equipped with the same aSi EPIDs assuring the stabilities of the beam output factors and the EPID signals. The calibration procedure of the aSi EPID here reported avoids measurements in solid water equivalent phantoms needed to implement the in vivo dosimetry method in the radiotherapy center. A tolerance level ranging between ±5% and ±6% (depending on the type of tumor) was estimated for the comparison between the reconstructed isocenter dose, D(iso) and the computed dose D(iso,TPS) by the treatment planning system (TPS).

Antenatal diagnosis and obstetric management of cystic hygroma occurring in twin pregnancies. A case report.

The lymphatic system has an early development in the embryo. Usually, its development is complete by the 40th postconceptional day. If this connection fails to develop, lymphatic stasis and dilatation of the lymphatic channels may occur, causing a number of pathologies such as: lymphangiomas, lymphangiectasis and cystic hygromas. Prenatal diagnosis can be made during the first trimester of pregnancy by ultrasonographic examination. A case of a twin pregnancy associated with cystic hygroma and bilateral hypoplasia of lower and upper limbs of both foetuses without chromosomal abnormalities is reported.

[Reduced neuronal nitric oxide synthetase and c-protein kinase levels in Alzheimer's disease]. / Disminución de los niveles de óxido nítrico sintasa y proteína quinasa C neuronales en la enfermedad de Alzheimer.

INTRODUCTION: Alzheimer's disease is characterized by a general and progressive dementia and by the presence of beta-amiloide deposits. OBJECTIVE: The levels of neuronal nitric oxide synthase (NOS) and protein kinase C (PKC), and the relationship between these proteins, the free-radical theory and the high level of beta-amiloide in Alzheimer's disease, have been studied. MATERIAL AND METHODS: The study has been performed in samples of Alzheimer's disease (superior, medial and inferior regions of temporalis gyrus) from control individuals and patients. The tissue was homogenized and the proteins were analyzed using monoclonal antibodies for NOS and PKC. RESULTS: Lower levels of neuronal constitutive NOS (37% +/- 2.5 and 52% +/- 3.0) in Alzheimer's disease derived superior and inferior temporalis gyrus, respectively, were observed. No changes were found in superior temporalis gyrus in PKC isoforms levels, involved in the processing for the beta-amiloide precursor protein. In the medial and inferior regions the PKC level was 5% +/- 0.5 to 22% +/- 3.0. CONCLUSIONS: These results could be related with an imbalance in the superoxide/nitric oxide ratio as a consequence of the non-inhibition of lipoxygenase, and with a neurotransmission dysfunction due, all this, to the decrease of nitric oxide levels. On the other hand, a relationship could be proposed between the high concentrations of beta-amiloide and the decrease in PKC levels in Alzheimer's disease.

Disminución de los niveles de óxido nítrico sintasa y proteína quinasa C neuronales en la enfermedad de Alzheimer / Reduced neuronal nitric oxide synthetase and C protein kinase levels in Alzheimer's disease

Introducción. La enfermedad de Alzheimer se caracteriza por demencia general y progresiva, así como por la presencia de depósitos de Beta-amiloide. Objetivo. Se han estudiado los niveles de óxido nítrico sintasa (NOS) y proteína quinasa C (PKC) neuronales para establecer una relación entre estas proteínas, la teoría de los radicales libres y los niveles elevados de Beta-amiloide en la enfermedad de Alzheimer (EA). Material y métodos. El estudio se ha llevado a cabo en muestras de EA (regiones superior, media e inferior del gyrus temporal) de individuos control y de pacientes. El tejido se homogeneizaba y el análisis de las proteínas se realizaba con anticuerpos monoclonales para NOS y PKC. Resultados. Se han detectado niveles más bajos de NOS neuronal constitutiva (37 por ciento ñ 2,5 y 52 por ciento ñ 3,0) en gyrus temporal superior e inferior de pacientes con EA, respectivamente. No se encontraron cambios en la región superior en los niveles de las isoformas de PKC implicadas en el procesamiento del precursor proteico del Beta-amiloide. En la región media e inferior, el nivel de PKC fue del 5 por ciento ñ 0,5 al 22 por ciento ñ 3,0. Conclusiones. Estos resultados podrían relacionarse con un desequilibrio en la razón superóxido/óxido nítrico como consecuencia de la desinhibición de la lipooxigenasa, y con una disfunción en la neurotransmisión, todo ello debido a la disminución de los niveles de óxido nítrico.Por otra parte, podría existir relación entre las altas concentraciones de Beta-amiloide y la disminución de los niveles de PKC en la EA (AU)

Endothelin-1 effect on tyrosine phosphorylation and on tyrosine phosphatase (PTP-1C) translocation in rabbit platelets.

This study examined the temporal relationships of endothelin-1-stimulated rabbit platelets tyrosine phosphorylated proteins. The effect of endothelin-1 on tyrosine phosphorylation was dose- and time-dependent and caused a rapid tyrosine phosphorylation of three groups of proteins in the molecular mass range 70-100 kDa, 100-150 kDa and 150-200 kDa. Significant protein tyrosine phosphatase activity and amount were found to be associated with the cytoskeleton of endothelin-1-stimulated rabbit platelets. Under our experimental conditions, translocation from the cytosolic fraction to the cytoskeleton reached its highest levels within 10-20 sec of endothelin-1 stimulation. Endothelin-1-induced translocation of protein tyrosine phosphatase, associated with the increase in its activity was demonstrated by immunoblotting and immunoelectron microscopy.

Protein tyrosine phosphatase activity modulation by endothelin-1 in rabbit platelets.

Protein tyrosine phosphorylation, modulated by the rate of both protein tyrosine kinase and protein tyrosine phosphatase activities, is critical for cellular signal transduction cascades. We report that endothelin-1 stimulation of rabbit platelets resulted in a dose- and time-dependent tyrosine phosphorylation of four groups of proteins in the molecular mass ranges of 50, 60, 70-100 and 100-200 kDa and that one of these corresponds to focal adhesion kinase. This effect is also related to the approximately 60% decrease in protein tyrosine phosphatase activity. Moreover, this inhibited activity was less sensitive to orthovanadate. In the presence of forskolin that increases the cAMP level a dose-dependent inhibition of the endothelin-stimulated tyrosine phosphorylation of different protein substrates and a correlation with an increase in the protein tyrosine phosphatase activity (11.6-fold compared to control) have been found. Further studies by immunoblotting of immunoprecipitated soluble fraction with anti-protein tyrosine phosphatase-1C from endothelin-stimulated platelets have demonstrated that the tyrosine phosphorylation of platelet protein tyrosine phosphatase-1C is correlated with the decrease in its phosphatase activity. As a consequence, modulation and regulation by endothelin-1 in rabbit platelets can be proposed through a cAMP-dependent pathway and a tyrosine phosphorylation process that may affect some relevant proteins such as focal adhesion kinase.

Effect of cAMP and cGMP on endothelin-stimulated tyrosine phosphorylation in rabbit platelets.

Activation of platelets by different agents results in the increased tyrosine phosphorylation of several substrate proteins. Thus, the effect of endothelin-1 on the stimulation of tyrosine phosphorylation in rabbit platelets can be inhibited by preincubation with forskolin, which increase the cAMP level. However, incubations of platelets with 8-Bromo-cGMP showed lower inhibitory effect. Forskolin produced a dose-dependent inhibition on three different protein substrates, with an IC50 of approximately 12.8, 4.0 and 8.0 microM in the three molecular mass ranges of 50, 60 and 100-200 kDa, respectively. These results show that the endothelin-stimulated tyrosine phosphorylation in rabbit platelets can be regulated by a novel pathway of platelet signal transduction in which the cAMP level could be more relevantly involved than cGMP in some molecular mass ranges of tyrosine phosphorylated proteins.

[Arterial hypertension during the rehabilitation phase of cerebral stroke. Study with nicardipine]. / L'ipertensione arteriosa nella fase riabilitativa dell'ictus cerebrale. Studio con nicardipina.

Arterial blood pressure was recorded in 15 hypertensive patients with ischemic cerebrovascular disease in the post-acute stage and under treatment with nicardipine, a drug with tropism for the muscular cells of cerebral vessels. Blood pressure was measured at rest and during rehabilitation sessions. Patients were periodically assessed by Doppler examination of the cerebral vessels in order to evaluate the effect of the drug on vascular resistance. A significant reduction of blood pressure was observed without changes in pulse rate and without significant side effects. Hemodynamic parameters showed reduced resistance of cerebral vessels. These findings confirm the need for accurate control of arterial blood pressure during neurologic rehabilitation; they also bear out the efficacy and safety of nicardipine in this clinical situation.