Low-level echogenicity in intraventricular hemorrhage versus ventriculitis

Serial cranial sonograms of 55 neonates with large perinatal intraventricular/intraparenchymal hemorrhages and moderate-to-severe posthemorrhagic hydrocephalus were reviewed. In all 55 patients, the ventricles were initially enlarged and filled with anechoic cerebrospinal fluid, which contained discrete hyperechoic fragments of hematoma. Between 7 and 25 days after the initial hemorrhagic episode, however, diffuse, low-level echogenicity appeared in the ventricles of 34 patients. The low-level echogenicity was transient and persisted for 7-59 days (average, 18 days). In 32 patients, low-level echogenicity was a benign finding associated with prior intraventricular hemorrhage. In two patients, the low-level echogenicity was associated with ventriculitis. Low-level echogenicity appeared, increased, then cleared, but reappeared with the onset of ventriculitis in these two patients. Thickening of the ependyma and abnormal periventricular echogenicity, signs of inflammation, were also present. Although low-level echogenicity may commonly be a benign finding, the possibility of ventriculitis should not be ignored.     

Chemogenetic Inactivation of Dorsal Anterior Cingulate Cortex Neurons Disrupts Attentional Behavior in Mouse

Attention is disrupted commonly in psychiatric disorders, yet mechanistic insight remains limited. Deficits in this function are associated with dorsal anterior cingulate cortex (dACC) excitotoxic lesions and pharmacological disinhibition; however, a causal relationship has not been established at the cellular level. Moreover, this association has not yet been examined in a genetically tractable species such as mice. Here, we reveal that dACC neurons causally contribute to attention processing by combining a chemogenetic approach that reversibly suppresses neural activity with a translational, touchscreen-based attention task in mice. We virally expressed inhibitory hM4Di DREADD (designer receptor exclusively activated by a designer drug) in dACC neurons, and examined the effects of this inhibitory action with the attention-based five-choice serial reaction time task. DREADD inactivation of the dACC neurons during the task significantly increased omission and correct response latencies, indicating that the neuronal activities of dACC contribute to attention and processing speed. Selective inactivation of excitatory neurons in the dACC not only increased omission, but also decreased accuracy. The effect of inactivating dACC neurons was selective to attention as response control, motivation, and locomotion remain normal. This finding suggests that dACC excitatory neurons play a principal role in modulating attention to task-relevant stimuli. This study establishes a foundation to chemogenetically dissect specific cell-type and circuit mechanisms underlying attentional behaviors in a genetically tractable species.     

Vaccine for AIDS and Ebola virus infection

Ebola virus and HIV present challenges for vaccine development because natural immunity to these viruses is difficult to find, and there are no immune correlates of protection in humans. Modern molecular genetic, virologic and immune analyses have been used to rationally identify promising approaches based on animal model and human clinical studies. Improved vaccine candidates have been defined for HIV, and a promising Ebola vaccine have conferred protection in non-human primates. Further evaluation in humans will allow an assessment of their potential efficacy and point the way to the development of more successful vaccines.     

The international collaborative study of maternal phenylketonuria: status report 1994

Neonatal screening for phenylketonuria (PKU) has created a problem as females with PKU are reaching child-bearing age. Surveys have revealed that maternal phenylalanine blood concentrations greater than 1200 μmol/l are associated with fetal microcephaly, congenital heart defects and intrauterine growth retardation. It is estimated that as many as 3000 hyperphenylalaninemic females may be at risk of producing these fetal abnormalities. To examine this problem, the international maternal PKU collaborative study was developed to evaluate the efficacy of a phenylalanine-restricted diet in reducing fetal morbidity. Preliminary findings have indicated that phenylalanine restriction should begin before conception for females with PKU planning a pregnancy. Dietary control should maintain maternal blood phenylalanine levels between 120 and 360 μmol/l and should provide adequate energy, protein, vitamin and mineral intake. Pregnant hyperphenylalaninemic females who achieved metabolic control after conception or by the 10th week of pregnancy had a better offspring outcome than anticipated. The results of 402 pregnancies are reviewed.     

Liposomal amphotericin B in hepatic candidosis

A 4 year old girl treated with a standard chemotherapy protocol for acute lymphoblastic leukaemia developed hepatic candidosis during the consolidation phase. This relapsed after a prolonged course of amphotericin B and flucytosine. An eight week course of liposomal amphotericin produced a marked clinical improvement which was sustained for one year. A subsequent relapse was associated with transformation to myelodysplastic leukaemia.