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Magnoni S.,University of Milan | Tedesco C.,University of Milan | Carbonara M.,University of Milan | Pluderi M.,Fondazione IRCCS CaGranda Ospedale Maggiore Policlinico | And 2 more authors.
Critical Care Medicine | Year: 2012

Objective: To clarify the dynamics of glucose delivery to the brain and the effects of changes in blood glucose after severe traumatic brain injury. Design: Retrospective analysis of a prospective observational cohort study. Setting: Neurosurgical intensive care unit of a university hospital. Patients: Seventeen patients with acute traumatic brain injury monitored with cerebral and subcutaneous microdialysis. Interventions: None. Measurements and Main Results: For continuous, accurate systemic monitoring, glucose was measured in the interstitial space of subcutaneous adipose tissue using microdialysis, and 39 specific episodes of spontaneous rises in glucose were identified. During these episodes, there was a significant positive linear relationship between systemic glucose levels and brain glucose concentrations measured by microdialysis (p < .0001). The basal lactate/pyruvate ratio, with a threshold of 25, was adopted to distinguish between disturbed and presumably preserved cerebral oxidative metabolism. Using normal vs. elevated lactate/pyruvate ratio as variable factor, the relationship between brain and systemic glucose during the episodes could be described by two significantly distinct parallel lines (p = .0001), which indicates a strong additive effect of subcutaneous glucose and lactate/pyruvate ratio in determining brain glucose. The line describing the relationship under disturbed metabolic conditions was lower than in presumably intact metabolic conditions, with a significant difference of 0.648 ± 0.192 mM (p = .002). This let us to accurately predict that in this situation systemic glucose concentrations in the lower range of normality would result in critical brain glucose levels. Conclusions: The linear relationship between systemic and brain glucose in healthy subjects is preserved in traumatic brain-injured patients. As a consequence, in brain tissue where oxidative metabolism is disturbed, brain glucose concentrations might possibly drop below the critical threshold of 0.8 mM to 1.0 mM when there is a reduction in systemic glucose toward the lower limits of the "normal" range. © 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.

Bianchi C.,Rehabilitation Unit | Baiardi P.,Valutazioni Biologiche e Farmacologiche | Khirani S.,Fondazione IRCCS CaGranda Ospedale Maggiore Policlinico | Cantarella G.,Fondazione IRCCS Ca Granda ospedale Maggiore Policlinico
American Journal of Physical Medicine and Rehabilitation | Year: 2012

OBJECTIVE: The aim of this study was to ascertain whether an objective cough measure relates to the risk of pulmonary complications in dysphagic patients with persistent tracheobronchial aspiration. DESIGN: This is a retrospective observational study involving 55 dysphagic patients who underwent a modified barium swallow study and pulmonary function tests including cough peak flow measurement. The results were compared between subjects with and without pulmonary complications because of aspiration. RESULTS: The 18 patients (33%) with pulmonary complications had significantly lower mean cough peak flow values (202.2 ± 68.8 vs. 303.9 ± 80.7 liters/min; P < 0.001) than those without pulmonary complications. The finding of tracheobronchial coating in a modified barium swallow was not related to the occurrence of pulmonary morbidity. Receiver operating characteristic curve analysis showed that a CPF level lower than 242 liters/min predicted the development of pulmonary complications with a sensitivity of 77% and a specificity of 83%; the positive and negative predictive values were 65% and 90%, respectively. CONCLUSIONS: Our findings indicate that cough peak flow is a valuable predictor of respiratory prognosis in chronic aspiration. This finding suggests a new rehabilitation strategy aimed at improving cough flows for dysphagic patients. Copyright © 2012 Lippincott Williams & Wilkins.

Riccio M.E.,University of Geneva | Buhler S.,University of Geneva | Nunes J.M.,University of Geneva | Vangenot C.,University of Geneva | And 37 more authors.
International Journal of Immunogenetics | Year: 2013

We present here the results of the Analysis of HLA Population Data (AHPD) project of the 16th International HLA and Immunogenetics Workshop (16IHIW) held in Liverpool in May-June 2012. Thanks to the collaboration of 25 laboratories from 18 different countries, HLA genotypic data for 59 new population samples (either well-defined populations or donor registry samples) were gathered and 55 were analysed statistically following HLA-NET recommendations. The new data included, among others, large sets of well-defined populations from north-east Europe and West Asia, as well as many donor registry data from European countries. The Gene[rate] computer tools were combined to create a Gene[rate] computer pipeline to automatically (i) estimate allele frequencies by an expectation-maximization algorithm accommodating ambiguities, (ii) estimate heterozygosity, (iii) test for Hardy-Weinberg equilibrium (HWE), (iv) test for selective neutrality, (v) generate frequency graphs and summary statistics for each sample at each locus and (vi) plot multidimensional scaling (MDS) analyses comparing the new samples with previous IHIW data. Intrapopulation analyses show that HWE is rarely rejected, while neutrality tests often indicate a significant excess of heterozygotes compared with neutral expectations. The comparison of the 16IHIW AHPD data with data collected during previous workshops (12th-15th) shows that geography is an excellent predictor of HLA genetic differentiations for HLA-A, -B and -DRB1 loci but not for HLA-DQ, whose patterns are probably more influenced by natural selection. In Europe, HLA genetic variation clearly follows a north to south-east axis despite a low level of differentiation between European, North African and West Asian populations. Pacific populations are genetically close to Austronesian-speaking South-East Asian and Taiwanese populations, in agreement with current theories on the peopling of Oceania. Thanks to this project, HLA genetic variation is more clearly defined worldwide and better interpreted in relation to human peopling history and HLA molecular evolution. © 2012 Blackwell Publishing Ltd.

Longhi L.,University of Milan | Orsini F.,Istituto di Ricerche Farmacologiche Mario Negri | De Blasio D.,Istituto di Ricerche Farmacologiche Mario Negri | De Blasio D.,University of Chieti Pescara | And 5 more authors.
Critical Care Medicine | Year: 2014

Objective: Mannose-binding lectin protein is the activator of the lectin complement pathway. Goals were 1) to investigate mannose-binding lectin expression after human and experimental traumatic brain injury induced by controlled cortical impact and 2) to evaluate whether mannose-binding lectin deletion is associated with reduced sequelae after controlled cortical impact. Design: Translational research, combining a human/experimental observational study and a prospective experimental study. Setting: University hospital/research laboratory. PATIENTS AND Subjects: Brain-injured patients, C57Bl/6 mice, and mannose-binding lectin-A and mannose-binding lectin-C double-knockout (-/-) mice. Interventions: Using anti-human mannose-binding lectin antibody, we evaluated mannose-binding lectin expression in tissue samples from six patients who underwent surgery for a cerebral contusion. Immunohistochemistry was also performed on tissues obtained from mice at 30 minutes; 6, 12, 24, 48, and 96 hours; and 1 week after controlled cortical impact using anti-mouse mannose-binding lectin-A and mannose-binding lectin-C antibodies. We evaluated the effects of mannose-binding lectin deletion in wild-type and mannose-binding lectin-A and mannose-binding lectin-C double-knockout mice. Functional outcome was evaluated using the neuroscore and beam walk tests for 4 weeks postinjury (n = 11). Histological injury was evaluated by comparing neuronal cell counts in the cortex adjacent to the contusion (n = 11). Measurements and main results: Following human traumatic brain injury, we observed mannose-binding lectin-positive immunostaining in the injured cortex as early as few hours and up to 5 days postinjury. Similarly in mice, we observed mannose-binding lectin-C-positive immunoreactivity in the injured cortex beginning 30 minutes and persisting up to 1 week postinjury. The extent of mannose-binding lectin-A expression was lower when compared with that of mannose-binding lectin-C. We observed attenuated sensorimotor deficits in mannose-binding lectin (-/-) mice compared with wild-type mice at 2-4 weeks postinjury. Furthermore, we observed reduced cortical cell loss at 5 weeks postinjury in mannose-binding lectin (-/-) mice compared with wild-type mice. Conclusions: Mannose-binding lectin expression was documented after traumatic brain injury. The reduced sequelae associated with mannose-binding lectin absence suggest that mannose-binding lectin modulation might be a potential target after traumatic brain injury. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.

Vercellini P.,University of Milan | Bracco B.,University of Milan | Mosconi P.,Mario Negri Institute for Pharmacological Research | Roberto A.,Mario Negri Institute for Pharmacological Research | And 3 more authors.
Fertility and Sterility | Year: 2016

Objective To assess the proportion of patients satisfied with their treatment before and after a systematic change from norethindrone acetate to dienogest as the first-line progestin for symptomatic endometriosis. Design Before and after study. Setting Academic department. Patient(s) The last 90 new consecutive endometriosis patients in whom norethindrone acetate was used, and the first 90 new consecutive endometriosis patients in whom dienogest was used. Intervention(s) Norethindrone acetate at the oral dose of 2.5 mg once a day until June 6, 2013, then dienogest at the oral dose of 2 mg once a day thereafter. Main Outcome Measure(s) Degree of satisfaction with treatment after 6 months of progestin therapy and assessment of any variations in pain symptoms, psychological status, sexual function, or health-related quality of life associated with the introduction of dienogest. Result(s) The proportion of satisfied plus very satisfied women after 6 months of treatment was 71% in the "before" period (norethindrone acetate) and 72% in the "after" period (dienogest). The implementation of dienogest was not associated with statistically significant ameliorations in overall pain relief, psychological status, sexual functioning, or health-related quality of life. Treatment was well tolerated by 58% of norethindrone acetate users compared with 80% of dienogest users. After dienogest implementation, the absolute risk reduction in the occurrence of any side effect was 13.9% (95% confidence interval, 0.8%-28.6%). Conclusion(s) Considering the large difference in the cost of the two drugs, dienogest should be suggested selectively in women who do not tolerate norethindrone acetate. © 2016 American Society for Reproductive Medicine.

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