Prognostic value of diffusion-weighted imaging summation scores or apparent diffusion coefficient maps in newborns with hypoxic-ischemic encephalopathy

Background

The diagnostic and prognostic assessment of newborn infants with hypoxic-ischemic encephalopathy (HIE) comprises, among other tools, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps.

Objective

To compare the ability of DWI and ADC maps in newborns with HIE to predict the neurodevelopmental outcome at 2 years of age.

Materials and methods

Thirty-four term newborns with HIE admitted to the Neonatal Intensive Care Unit of Modena University Hospital from 2004 to 2008 were consecutively enrolled in the study. All newborns received EEG, conventional MRI and DWI within the first week of life. DWI was analyzed by means of summation (S) score and regional ADC measurements. Neurodevelopmental outcome was assessed with a standard 1–4 scale and the Griffiths Mental Developmental Scales - Revised (GMDS-R).

Results

When the outcome was evaluated with a standard 1–4 scale, the DWI S scores showed very high area under the curve (AUC) (0.89) whereas regional ADC measurements in specific subregions had relatively modest predictive value. The lentiform nucleus was the region with the highest AUC (0.78). When GMDS-R were considered, DWI S scores were good to excellent predictors for some GMDS-R subscales. The predictive value of ADC measurements was both region- and subscale-specific. In particular, ADC measurements in some regions (basal ganglia, white matter or rolandic cortex) were excellent predictors for specific GMDS-R with AUCs up to 0.93.

Conclusions

DWI S scores showed the highest prognostic value for the neurological outcome at 2 years of age. Regional ADC measurements in specific subregions proved to be highly prognostic for specific neurodevelopmental outcomes.     

Remifentanil in neonatal intensive care and anaesthesia practice

Remifentanil is a relatively new ultrashort action synthetic opioid. Studies on the use of remifentanil in neonatology have emerged demonstrating its effectiveness and safety in neonates. The present study describes the use of remifentanil in both full‐term and premature newborns, highlighting the theoretical benefits for this population in terms of both neonatal intensive care and anaesthesia. A Medline search was undertaken of all reviews and reports about the use of remifentanil in neonates published between 1996 and 2009 using MeSH search terms ‘remifentanil’, ‘analgesia’, ‘anaesthesia’, ‘newborn’ and ‘neonate’. The review points that remifentanil has been used with advantages in newborns including preterm neonates and even for foetal anaesthesia. It proved to be a good option to attenuate the hemodynamic/endocrine markers of stress related to surgery. Owing to its unique pharmacokinetic profile, shorter extubation times can be achieved what makes the drug also a good option for short duration invasive procedures in NICUs (InSurE). A concern on its use is that the hemodynamic response (hypotension) may become significant when the drug is associated to other drugs like sevoflurane. Conclusion: Remifentanil seems to be an effective and safely used opioid for neonatal intensive care and anaesthesia practice.     

Ex vivo evaluation of prolidase loaded chitosan nanoparticles for the enzyme replacement therapy.

Prolidase loaded chitosan nanoparticles were set up in order to suggest an innovative therapeutic approach for Prolidase Deficiency (PD), a rare autosomal inherited disorder of the connective tissue. The satisfactory drug loading efficiency (42.6+/-2.1%) as well as the suitable physical characteristics (mean diameter of 365.5+/-35.1nm and a positive zeta-potential of 17.94+/-0.12mV) was achieved. In order to verify the compatibility of the chitosan nanoparticles with cells, the influence of the nanoparticles on the growth and the viability (MTT assay) of cultured skin fibroblasts were determined: the nanoparticles showed a good biocompatibility up to 5mug of chitosan/10,000 fibroblasts. Uptake of chitosan nanoparticles by fibroblasts was verified by confocal microscopy using FITC-labelled chitosan nanoparticles. The ex vivo experiments were performed by incubating different amounts of prolidase loaded chitosan nanoparticles with skin human fibroblasts from PD patients for scheduled times. The restored prolidase activity was quantitatively monitored by a capillary electrophoretic method and confirmed by cells morphological observations. Standing from the nanoparticles internalization, the enzymatic activity was progressively restored reaching the best value (about 66%) after 5 days of co-incubation. Moreover, prolidase loaded chitosan nanoparticles permitted to restore prolidase activity in PD fibroblasts for a prolonged period of time (8 days).     

Phosphodiesterase 11A (PDE11A) and genetic predisposition to adrenocortical tumors.

PURPOSE: We have reported previously nonsense inactivating mutations of the phosphodiesterase 11A (PDE11A) gene in patients with micronodular adrenocortical hyperplasia and Cushing syndrome. The aim of this study is to investigate the presence of somatic or germ-line PDE11A mutations in various types of adrenocortical tumors: ACTH-independent macronodular adrenocortical hyperplasia (AIMAH), adrenocortical adenoma (ACA), and adrenocortical cancer (ACC). EXPERIMENTAL DESIGN: PDE11A was sequenced in 117 adrenocortical tumors and 192 controls subjects; immunohistochemistry for PDE11A and tumor cyclic AMP levels were studied in a subgroup of adrenocortical tumors. RESULTS: One PDE11A inactivating mutation (R307X) was found in one ACA, 22 germ-line missense variants (18.8%) were found in adrenocortical tumors, and only 11 missense variants (5.7%) were found in controls. By comparing the common mutations, a higher frequency of mutations in adrenocortical tumors than in age/sex-matched controls were observed [16% versus 10% in ACC, 19% versus 10% in ACA, and 24% versus 9% in AIMAH; odds ratio (OR), 3.53; P = 0.05]. Somatic DNA from adrenocortical tumors with missense variants showed a wild-type allelic loss. A significant difference between ACC and controls was observed for a polymorphism in exon 6 (E421E; OR, 2.1; P = 0.03) and three associated polymorphisms located in intron 10-exon 11-intron 11 (OR, 0.5; P = 0.01). In AIMAH/ACA, cyclic AMP levels were higher than in normal adrenals and decreased PDE11A immunostaining was present in adrenocortical tumors with PDE11A variants. CONCLUSIONS: The present investigation of a large cohort of adrenocortical tumors suggests that PDE11A sequence defects predispose to a variety of lesions (beyond micronodular adrenocortical hyperplasia) and may contribute to the development of these tumors in the general population.     

Prenatal diagnosis of metabolic diseases on chorionic villi obtained before the ninth week of pregnancy.

Nine pregnancies at risk for various metabolic disorders were monitored by prenatal diagnosis on chorionic villi obtained between the sixth and ninth weeks of pregnancy. A diagnosis of an affected fetus was made in five cases (Sandhoff, Tay-Sachs (2), Pompe's, GM1), while metachromatic leukodystrophy, GM1 (2), and Pompe's were excluded in four cases. It is concluded that chorionic villi are a reliable tissue for prenatal diagnosis of metabolic disorders also when obtained before the ninth week.     

Genotype- and experience-dependent susceptibility to depressive-like responses in the forced-swimming test

Abstract Rationale. The forced-swimming test (FST) is utilized to reproduce passive coping responses to stress that may model a relevant aspect of human depression in rodent species. Animals showing high levels of passive responses to the FST are assumed to model pathologically depressed individuals. Objectives. We evaluated sensitivity of FST-induced behavioral responses to the interaction between genetic and environmental influences. Methods. Behavioral responses to FST were evaluated in naive mice of the C57BL/6 and DBA/2 strains, in mice of both strains pre-exposed to FST 14 days before test, and in FST-experienced animals subsequently exposed to 12 days of stress experience (food restriction). Results. C57BL/6 mice are characterized by high propensity to adopt passive coping responses in the FST. Moreover, stress enhances FST-induced immobility in mice of the C57BL/6 strain but reduces this response in DBA/2 mice. Finally, FST-induced immobility in C57BL/6 mice is reduced by chronic treatment with clinically effective antidepressants. Conclusions. These results support the view that behavioral and neural responses to FST exhibited by C57BL/6 mice can be usefully exploited by pre-clinical research on depression. Electronic Publication