Temporal lobe dual pathology in malignant migrating partial seizures in infancy.

A child had the characteristic clinical and EEG pattern of migrating partial seizures in infancy with left temporal lobe atrophy, hippocampal sclerosis and cortical-subcortical blurring.Seizures were drug-resistant, with recurring episodes of status epilepticus. The child developed microcephaly with arrest of psychomotor development. Focal brain lesions, in the context of migrating partial seizures, have not been previously reported.[Published with video sequences].     

Downregulation of inflammatory markers by conjugated linoleic acid isomers in human cultured astrocytes

Objectives: Conjugated linoleic acid (CLA) isomers have been shown to possess anti-inflammatory activity in the central nervous system. In this study, we aimed to evaluate whether modulation of the fatty acid profile by the CLA isomers c9,t11 or t10,c12CLA was associated with changes in the expression of pro-inflammatory molecules in human astrocytes.

Methods: Cultured astrocytes were treated for 6 days with 100?µM fatty acids (c9,t11CLA or t10,c12CLA or oleic acid). Following the treatment, the fatty acid profile of the cell and pro-inflammatory molecule expression were assessed.

Results: Only the t10,c12CLA isomer induced a significant decrease in arachidonic acid and increased the ratio of docosahexaenoic acid/eicosapentaenoic acid, which constitutes indirect evidence of peroxisome proliferator-activated receptor alpha activation. Inhibition of tumour necrosis factor-α, interleukin-1β, and RANTES expression was observed in astrocytes treated with c9,t11CLA and t10,c12CLA.

Discussion: Current data demonstrate that CLA isomers, particularly t10,c12, may affect neuroinflammation by reducing the pro-inflammatory molecules in cultured astrocytes, suggesting a potential nutritional role of CLA isomers in modulating the astrocyte inflammatory response.     

Risk of Adverse Pregnancy Outcomes in Women with CKD

CKD is increasingly prevalent in pregnancy. In the Torino-Cagliari Observational Study (TOCOS), we assessed whether the risk for adverse pregnancy outcomes is associated with CKD by comparing pregnancy outcomes of 504 pregnancies in women with CKD to outcomes of 836 low-risk pregnancies in women without CKD. The presence of hypertension, proteinuria (>1 g/d), systemic disease, and CKD stage (at referral) were assessed at baseline. The following outcomes were studied: cesarean section, preterm delivery, and early preterm delivery; small for gestational age (SGA); need for neonatal intensive care unit (NICU); new onset of hypertension; new onset/doubling of proteinuria; CKD stage shift; “general” combined outcome (preterm delivery, NICU, SGA); and “severe” combined outcome (early preterm delivery, NICU, SGA). The risk for adverse outcomes increased across stages (for stage 1 versus stages 4–5: “general” combined outcome, 34.1% versus 90.0%; “severe” combined outcome, 21.4% versus 80.0%; P<0.001). In women with stage 1 CKD, preterm delivery was associated with baseline hypertension (odds ratio [OR], 3.42; 95% confidence interval [95% CI], 1.87 to 6.21), systemic disease (OR, 3.13; 95% CI, 1.51 to 6.50), and proteinuria (OR, 3.69; 95% CI, 1.63 to 8.36). However, stage 1 CKD remained associated with adverse pregnancy outcomes (general combined outcome) in women without baseline hypertension, proteinuria, or systemic disease (OR, 1.88; 95% CI, 1.27 to 2.79). The risk of intrauterine death did not differ between patients and controls. Findings from this prospective study suggest a “baseline risk” for adverse pregnancy-related outcomes linked to CKD.     

Addition of iron to erythropoiesis-stimulating agents in cancer patients: a meta-analysis of randomized trials

Background  

Iron supplementation could improve the hematopoietic response of erythropoiesis-stimulating agents (ESAs) used for chemotherapy-induced anemia.     

Heart Rate Variability and Cardio-respiratory Coupling During Sleep in Patients Prior to Bariatric Surgery

Obesity is associated with increased cardiac risk of morbidly and mortality and for the development and progression of obstructive sleep apnea (OSA). Severity of obesity negatively affects the heart rate variability (HRV) in patients with indication for bariatric surgery (BS). The purpose of this study is to determine if the severity of obesity alters the autonomic cardiac regulation and the cardio-respiratory coupling during sleep using spectral analysis of HRV and respiration variability signals (RS) in patients prior to BS. Twenty-nine consecutive preoperative BS and ten subjects (controls) underwent polysomnography. The spectral and cross-spectral parameters of the HRV and RS were computed during different sleep stages (SS). Spectral analysis of the HRV and RV indicated lower respiration regularity during sleep and a lower HRV in obese patients (OP) during all SS when compared with controls (p < 0.05). Severely (SO) and super-obese patients (SOP) presented lower values of low frequency/high frequency (LF/HF) ratio and LF power during REM sleep and higher HF power (p < 0.05), while morbidly obese (MO) patients presented lower LF/HF ratio and LF power in SS-S2 and higher HF power when compared to controls (p < 0.05). The cross-spectral parameters showed that SOP presented lower percentage of tachogram power coherent with respiration in SS-S3 when compared to controls (p < 0.05). Patients prior to BS presented altered HRV and RV in all SS. SO, MO, and SOP presented altered cardio-respiratory coupling during sleep, and these alterations are related with severity of obesity and OSA parameters.     

Polarization dictates iron handling by inflammatory and alternatively activated macrophages

Background

Macrophages play a key role in iron homeostasis. In peripheral tissues, they are known to polarize into classically activated (or M1) macrophages and alternatively activated (or M2) macrophages. Little is known on whether the polarization program influences the ability of macrophages to store or recycle iron and the molecular machinery involved in the processes.

Design and Methods

Inflammatory/M1 and alternatively activated/M2 macrophages were propagated in vitro from mouse bone-marrow precursors and polarized in the presence of recombinant interferon-γ or interleukin-4. We characterized and compared their ability to handle radioactive iron, the characteristics of the intracellular iron pools and the expression of molecules involved in internalization, storage and export of the metal. Moreover we verified the influence of iron on the relative ability of polarized macrophages to activate antigen-specific T cells.

Results

M1 macrophages have low iron regulatory protein 1 and 2 binding activity, express high levels of ferritin H, low levels of transferrin receptor 1 and internalize – albeit with low efficiency -iron only when its extracellular concentration is high. In contrast, M2 macrophages have high iron regulatory protein binding activity, express low levels of ferritin H and high levels of transferrin receptor 1. M2 macrophages have a larger intracellular labile iron pool, effectively take up and spontaneously release iron at low concentrations and have limited storage ability. Iron export correlates with the expression of ferroportin, which is higher in M2 macrophages. M1 and M2 cells activate antigen-specific, MHC class II-restricted T cells. In the absence of the metal, only M1 macrophages are effective.

Conclusions

Cytokines that drive macrophage polarization ultimately control iron handling, leading to the differentiation of macrophages into a subset which has a relatively sealed intracellular iron content (M1) or into a subset endowed with the ability to recycle the metal (M2).     

Erlotinib as maintenance therapy in patients with advanced non-small cell lung cancer: a pooled analysis of three randomized trials

Three randomized trials (SATURN, ATLAS and IFCT-GFPC 0502) have demonstrated that the oral antiepidermal growth factor receptor tyrosine kinase inhibitor erlotinib can improve progression-free survival (PFS) and overall survival (OS), as maintenance therapy after first-line chemotherapy in advanced non-small cell lung cancer. We pooled the results of these three trials by performing a meta-analysis of hazard ratios (HRs) and the 95% confidence intervals (CIs) for the PFS and the OS for maintenance erlotinib versus observation, standard therapy or placebo. The benefits in the predefined subgroups of patients [according to histology, sex, performance status (PS), and smoking status] were assessed. The OS was superior in the 963 patients treated with erlotinib than in the 979 nontreated patients [HR=0.87 (P=0.003), corresponding to a 13% reduction in the risk of death. The pooled HR for the PFS is 0.76 (P<0.00001), corresponding to a 24% lower risk of being progression free]. All the patients in the subgroup analysis experienced a benefit from erlotinib and, in particular, never-smoking women with nonsquamous histology with a PS of 0. Both responders and those with stable disease obtain PFS benefit. The addition of maintenance erlotinib significantly improves PFS and OS in patients with advanced non-small cell lung cancer who had not progressed after four cycles of first-line chemotherapy. The benefit does not seem to be limited to a particular subgroup, although it is more pronounced in never-smoking women patients with nonsquamous carriers with a PS of 0.     

Is Early Tracheostomy a Risk Factor for Mediastinitis after Median Sternotomy?

Abstract   Early tracheostomy may increase the risk of mediastinitis after median sternotomy. Patients who had postoperative tracheostomy after cardiac surgery in the period 2000-2005 were retrospectively analyzed (total: 5095 patients) to evaluate the incidence of mediastinitis and sternal wound infections. Fifty-seven cases (1.1% of all operated patients) had postoperative tracheostomy at an average 5.6 ± 0.7 days postoperatively. None of these patients had mediastinitis. Eleven cases of aseptic sternal instability and ten cases of mild-to-moderate infection limited to subcutaneous planes were observed. There was no correlation between the time to performance of tracheostomy and the isolation of bacteria from the thoracic wounds (p = 0.61). The bacterial strains isolated from subcutaneous infection were qualitatively and quantitatively different from those isolated from bronchial secretions. We conclude that in this study there is no demonstrable link between early tracheostomy after sternotomy and mediastinitis. Early tracheostomy should not be denied due to concerns of increasing the risk of mediastinitis.     

Typing of the immunological system in human embryos by coelocentesis

Coelocentesis offers a new opportunity for gaining access to the human embryos from 28 d postfertilization. However, while some studies about its biochemical composition have been reported, our knowledge about immunological pattern of this compartment is still limited. For this reason, we studied the human coelomic fluids sampled from 6.6 to 10 wk of gestation. The majority of cellular population consisted in mesenchymal/epithelial cells. In fluids sampled before 10 wk we found only a preT Cell Receptor expression and an absence or a very low frequency of B lymphocytes, T lymphocytes and NK (natural killer) antigens. These preliminary data suggest that the immunological system in human embryos could be in the ideal conditions to start a process of tolerance induction.