Disturbed sleep is one of the most common complaints following traumatic brain injury (TBI) and worsens morbidity and long-term sequelae. Further, sleep and TBI share neurophysiologic underpinnings with direct relevance to recovery from TBI. As such, disturbed sleep and clinical sleep disorders represent modifiable treatment targets to improve outcomes in TBI. This paper presents key findings from a national working group on sleep and TBI, with a specific focus on the testing and development of sleep-related therapeutic interventions for mild TBI (mTBI). First, mTBI and sleep physiology are briefly reviewed. Next, essential empirical and clinical questions and knowledge gaps are addressed. Finally, actionable recommendations are offered to guide active and efficient collaboration between academic, industry, and governmental stakeholders.

Among the potential nonviral vectors for human gene therapy are DNA-liposome complexes. In a recent clinical study, this delivery system has been utilized. In this report, a novel cationic lipid, dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium (DMRIE), has been substituted into the DNA-liposome complex with dioleoyl phosphatidylethanolamine (DOPE), which both improves transfection efficiencies and allows increased doses of DNA to be delivered in vivo. The safety and toxicity of this DNA-liposome complex has been evaluated in two species, mice and pigs. The efficacy of DMRIE/DOPE in inducing an antitumor response in mice after transfer of a foreign MHC has been confirmed. No abnormalities were detected after administration of up to 1,000-fold higher concentrations of DNA and lipid than could be tolerated in vivo previously. Examination of serum biochemical enzymes, pathologic examination of tissue, and analysis of cardiac function in mice and pigs revealed no toxicities related to this treatment. This improved cationic lipid formulation is well-tolerated in vivo and could therefore allow higher dose administration and potentially greater efficiency of gene transfer for gene therapy.

ABSTRACT. Twenty-two of 23 consecutive infants with bronchiolitis, 5.5 f 3.5 mo of age, showed a 1.9 f 1.4% increase in body weight, increased urinary osmolality of 737 f 193 mmol/L with low plasma osmolality of 275 f 4 mmol/L, and markedly elevated plasma antidiuretic hormone (ADH) levels of 114 f 225 pg/mL. Increased ADH, which usually suppresses plasma renin activity, was associated with increased plasma renin activity of 11-55 ng angiotensin l/mL/h (normal for age < l o ng angiotensin 1/ mL/h). Hyperaldosteronism was evident from the low fractional excretion of sodium of 0.27 f 0.2% and high fractional excretion of potassium of 21 f 15%. Serum sodium concentrations were normal. All of the pathologic findings returned to normal when the bronchiolitis subsided. A control group of 10 infants with nonrespiratory febrile illness did not show any of the above abnormalities. Thus, bronchiolitis of infancy is characterized by both increased ADH secretion and hyperreninemia with secondary hyperaldosteronism, which induce water retention but counterbalance each other with respect to serum sodium. Increased ADH secretion as well as increased plasma renin activity are not "inappropriate," but rather suggest a response to the perception of hypovolemia by intrathoracic receptors. We therefore conclude that the clinical management of bronchiolitis requires close monitoring of body wt and plasma osmolality-urinary osmolality relationship; serum sodium levels may be misleading. (Pediatr Res 27: 204-209,1990) Abbreviations ADH, antidiuretic hormone SIADH, syndrome of inappropriate ADH secretion PRA, plasma renin activity FE, fractional excretion Uosm, urinary osmolality Posm, plasma osmolality Ang, angiotensin It has been our clinical impression that infants with severe bronchiolitis develop facial puffiness that lessens and disappears as the respiratory distress improves. The possibility that excess fluid retention causes this appearance has been reinforced by the observation that concomittant with the loss of facial puffiness, a reduction in body wt occurs. The association of (SIADH) has