Neonatal hemochromatosis and Martinez-Frias syndrome of intestinal atresia and diabetes mellitus in a consanguineous newborn.

Neonatal hemochromatosis is a heterogeneous disorder of iron metabolism characterized by hepatic failure and marked iron accumulation in liver and extrahepatic tissues. Autosomal recessive transmission is found in most cases. Neonatal hemochromatosis shares cellular features with the adult disease but is clinically and genetically distinct, the causal gene(s) being presently unknown. We report on a newborn from consanguineous parents who presented with multiple congenital anomalies and neonatal hemochromatosis. The syndrome consisted of intra-uterine growth retardation, intestinal atresia, gallbladder aplasia and diabetes mellitus, and fitted with the diagnosis of Martinez-Frias syndrome, a very rare autosomal recessive phenotype, the gene of which remains to be identified. We suggest that neonatal hemochromatosis may be part of the Martinez-Frias syndrome. Molecular analyses in this and other reported patients with the Martinez-Frias syndrome should shed light on gut development and iron metabolism.

Nitrated plasma albumin as a marker of nitrative stress and neonatal encephalopathy in perinatal asphyxia.

Reactive nitrogen species (RNS) have been shown to play a major role in the pathophysiology of hypoxic-ischemic cerebral injury. Using a novel sensitive ELISA allowing the quantification of nitrated albumin (nitroalbumin) in plasma, we tested the hypothesis that perinatal asphyxia increases nitrating RNS generation by verifying whether the concentration of one of its target proteins is correlated with the clinical outcome. We assayed nitroalbumin in 114 plasma samples collected during the first hour, at day 1, and at day 4 of life from 48 term newborns suffering from perinatal asphyxia and correlated this marker with neurological and systemic neonatal outcomes. Nitroalbumin levels at day 1, but not at days 0 and 4, were significantly increased in patients who developed moderate or severe encephalopathy compared to those who had a normal neurological evolution or developed mild encephalopathy (median: 14.4 ng/ml versus 7.3 ng/ml, respectively). In contrast, nitroalbumin concentration at day 1 was not associated with systemic complications. First-hour and fourth-day nitroalbumin concentrations did not differ with respect to the neonatal neurological course. At day 0, nitroalbumin levels also correlated with circulating leukocytes. We conclude that plasma nitroalbumin seems to be a specific marker of neurological injury after perinatal asphyxia and may serve as a secondary end-point in neuroprotective clinical trials.

Nuclear galectin-3 expression is an independent predictive factor of recurrence for adenocarcinoma and squamous cell carcinoma of the lung.

The tumor stage is the most powerful prognostic tool for predicting the survival rates of lung carcinoma patients. However, prognosis of individual patients is difficult in part because of the marked clinical heterogeneity among such patients. Galectins are involved in cell growth, apoptosis and cell migration features, and their diagnostic and prognostic values have already been demonstrated in various types of cancers. In the present paper we analyze the potential prognostic value of immunohistochemical galectin-3 expression in lung adenocarcinomas and squamous cell carcinomas. In all, 165 squamous cell carcinomas and 121 adenocarcinomas were immunostained for galectin-3. In each case the immunohistochemical analyses consisted of an evaluation of the percentage of tumor cells stained and the intensity of staining. An IP score (ie Intensity x Percentage) was thus determined for each lung carcinoma. A large majority of cases displayed galectin-3 expression. While the cytoplasmic staining in the squamous cell carcinomas was focal and moderately intense, the staining in the adenocarcinomas was diffuse and intense. The IP scores were significantly (P=0.0001) higher in the adenocarcinomas than in the squamous cell carcinomas. The difference in nuclear expression profiles between the two cancer types was statistically significant (P=0.0005). Cox multivariate analysis carried out on the patients' genders, the TNM classification and the galectin-3-related variables showed that of the galectin-3-related variables, only the nuclear location of galectin-3 was identified as a prognostic indicator of recurrence independent of the clinicopathological features characterizing the patients (P=0.02). The prognostic contribution of this latter variable was enhanced when the patients with relapse-free follow-ups longer than 8 months were considered (P=0.005). Galectin-3 immunohistochemical expression differs between squamous cell carcinomas and adenocarcinomas, but the nuclear expression of galectin-3 behaves as a significant prognostic predictor for all the cases as a group.