Phthalate-associated hypertension in premature infants: a prospective mechanistic cohort study.

BACKGROUND: Phthalates are associated with increased blood pressure in children. Large exposures to di-(2-ethylhexyl) phthalate (DEHP) among premature infants have been a cause for concern. METHODS: We conducted a prospective observational cohort study to determine if DEHP exposures are related to systolic blood pressure (SBP) in premature infants, and if this exposure is associated with activation of the mineralocorticoid receptor (MR). Infants were monitored longitudinally for 8 months from birth. Those who developed idiopathic hypertension were compared with normotensive infants for DEHP exposures. Appearance of urinary metabolites after exposure was documented. Linear regression evaluated the relationship between DEHP exposures and SBP index and whether urinary cortisol/cortisone ratio (a surrogate marker for 11ß-HSD2 activity) mediated those relationships. Urinary exosomes were quantified for sodium transporter/channel expression and interrogated against SBP index. RESULTS: Eighteen patients met the study criteria, nine developed transient idiopathic hypertension at a postmenstrual age of 40.6 ± 3.4 weeks. The presence of urinary DEHP metabolites was associated with prior IV and respiratory tubing DEHP exposures (p < 0.05). Both IV and respiratory DEHP exposures were greater in hypertensive infants (p < 0.05). SBP index was related to DEHP exposure from IV fluid (p = 0.018), but not respiratory DEHP. Urinary cortisol/cortisone ratio was related to IV DEHP and SBP index (p < 0.05). Sodium transporter/channel expression was also related to SBP index (p < 0.05). CONCLUSIONS: Increased blood pressure and hypertension in premature infants are associated with postnatal DEHP exposure. The mechanism of action appears to be activation of the MR through inhibition of 11ß-HSD2.

Herpes simplex virus infections in preterm infants.

OBJECTIVE: Neonatal herpes simplex virus infections cause significant neonatal mortality and morbidity, but the course and prognosis in preterm infants is not well documented. We performed a retrospective review of herpes simplex virus infections at out institution within the first 30 days after birth in infants who were born at <37 weeks to help better define the symptoms and signs of herpes simplex virus infections in preterm infants and to assist in prognosis. METHODS: Hospital databases were reviewed to identify culture- or polymerase chain reaction-proven cases of herpes simplex virus-1 or herpes simplex virus-2 infections that occurred in preterm newborns between 1989 and 2003. Maternal and neonatal histories, clinical features, and laboratory results were reviewed systematically. RESULTS: Ten preterm singletons and a set of twins were infected with herpes simplex virus-2 during the first month after birth. No mother had herpes simplex virus lesions at delivery, but a history of genital herpes simplex or other sexually transmitted infections was prevalent among the mothers. Infants presented with either disseminated disease or encephalitis. All infants with disseminated disease (n = 9) died, whereas the 3 infants with encephalitis survived. All infants in the cohort developed respiratory distress, and consistent with the prominence of respiratory symptoms, viral cultures of the respiratory tract were consistently positive. Ten of 12 infants received acyclovir, but despite treatment within 48 hours of symptoms, infants with disseminated disease deteriorated rapidly and died. Two of 3 infants who received high-dosage (60 mg/kg per day) acyclovir survived. CONCLUSIONS: Herpes simplex virus infections in preterm infants usually present during the first 2 weeks of life with respiratory distress and a high incidence of disseminated disease. Viral respiratory cultures have a high yield for documentation of infection. The morbidity of herpes simplex virus in this population may be attributable to a relatively immature immune system in this population. Additional studies are necessary to delineate the evolution of herpes simplex virus disease in preterm infants and the role of antiviral therapy in mitigating the sequelae of herpes simplex virus infections in this population.

Diagnosis and management of vein of galen aneurysmal malformations.

Vein of Galen aneurysmal malformations (VGAM) are rare intracranial vascular anomalies typically found in children. The anatomic landmark of a VGAM is the presence of multiple arteriovenous shunts draining into a dilated median prosencephalic vein, an embryonic vessel normally absent at the adult stage. This article reviews the developmental anatomy, the clinical presentation, and the current management of VGAM.

Neonatal mice lacking functional Fas death receptors are resistant to hypoxic-ischemic brain injury.

Neonatal hypoxia-ischemia (HI) upregulates Fas death receptor expression in the brain, and alterations in expression and activity of Fas signaling intermediates occur in neonatal brain injury. B6.MRL-Tnfrsf6(lpr) mice lacking functional Fas death receptors are protected from HI brain damage in cortex, striatum, and thalamus compared to wild-type mice. Expression of Fas death receptor and active caspases increase in the cortex after HI. In wild-type mice, the hippocampus is most severely injured, and the hippocampus is the only region not protected in the B6.MRL-Tnfrsf6(lpr) mice. The selective vulnerability of the hippocampus to injury correlates with (1) lower basal expression of [Fas-associated death-domain-like IL-1beta-converting enzyme]-inhibitory protein (FLIP), (2) increased degradation of spectrin to its 145 or 150 kDa breakdown product, and (3) a higher percentage of non-apoptotic cell death following neonatal HI. We conclude that Fas signaling via both extrinsic and intrinsic caspase cascades causes brain injury following neonatal HI in a region-dependent manner. Basal levels of endogenous decoy proteins may modulate the response to Fas death receptor signaling and provide a novel approach to understanding mechanisms of neonatal brain injury.

Survey of aggressive incidents experienced by community mental health staff.

The phenomenon of aggression experienced by community mental health staff is explored in the present study. Qualitative and quantitative data were elicited in a self-report questionnaire completed by 92 community mental health workers from a metropolitan Area Health Service. Findings indicate that 96% of community mental health workers experienced some form of aggression in the course of their work, 25% felt that their life had been threatened and 7% sustained physical injuries. Issues in need of attention are the normalization of aggression and subsequent lack of incident reporting, and the appropriateness of staff safety training for community mental health settings.