Headache trajectories in children and adolescents with new onset continuous headache.

Background: New daily persistent headache (NDPH) is a challenging and understudied primary headache disorder with no known effective treatment. Although the International Classification of Headache Disorders criteria require that the new onset continuous headache be present for at least three months before diagnosing NDPH, the biologic basis for when a new, continuous headache starts to behave as NDPH is unknown, and some pediatric headache experts consider that the minimum duration criterion could be shorter.

Methods: In this retrospective study, we reviewed the intake questionnaires and medical records of 5-17 year-olds seen in neurology clinic for headache at the Children's Hospital of Philadelphia.

Validity of self-reported migraine in adolescents and children.

Objective: To assess agreement for migraine day between self-report and diagnostic guidelines for children and adolescents using a headache diary.

Background: Trial guidelines recommend prospective collection of headache features and adoption of migraine day as an outcome measure, but there is no clear consensus on the definition of migraine day.

Methods: This is a secondary analysis of data from two projects-a prospective cohort study validating a pediatric scale of treatment expectancy and a clinical trial of occipital nerve blocks to treat status migrainosus.

Development of a text message-based headache diary in adolescents and children.

Background: International guidelines recommend diaries in migraine trials for prospective collection of headache symptoms. Studies in other patient populations suggest higher adherence with electronic diaries instead of pen-and-paper. This study examines the feasibility of a text message-based (texting) diary for children and adolescents with headache.

The spectrum of indomethacin-responsive headaches in children and adolescents.

Background: Headaches with marked, specific response to indomethacin occur in children, but the phenotypic spectrum of this phenomenon has not been well-studied.

Methods: We reviewed pediatric patients with headache showing ≥80% improvement with indomethacin, from seven academic medical centers.

Results: We included 32 pediatric patients (16 females).

Trigeminal Pain Responses in Obese ob/ob Mice Are Modality-Specific.

How obesity exacerbates migraine and other pain disorders remains unknown. Trigeminal nociceptive processing, crucial in migraine pathophysiology, is abnormal in mice with diet induced obesity. However, it is not known if this is also true in genetic models of obesity.

TAT-HSP70 Attenuates Experimental Lung Injury.

Sepsis, a poorly understood syndrome of disordered inflammation, is the leading cause of death in critically ill patients. Lung injury, in the form of acute respiratory distress syndrome (ARDS), is the most common form of organ injury in sepsis. The heat shock response, during which heat shock proteins (HSPs) are expressed, is an endogenous mechanism to protect cells from injury.

Orexinergic activity modulates altered vital signs and pituitary hormone secretion in experimental sepsis.

Objectives: Sepsis is a common, lethal poorly understood disorder affecting nearly a million Americans annually. The syndrome is characterized by altered cardiodynamics, respiration, metabolism, pituitary function, arousal, and impaired interaction among organ systems. The immunologic and endocrine systems, which are in part responsible for organ-organ communication, have been studied extensively in sepsis.

Enhanced Hsp70 expression protects against acute lung injury by modulating apoptotic pathways.

The Acute respiratory distress syndrome (ARDS) is a highly lethal inflammatory lung disorder. Apoptosis plays a key role in its pathogenesis. We showed that an adenovirus expressing the 70 kDa heat shock protein Hsp70 (AdHSP) protected against sepsis-induced lung injury.

Impaired hepatocellular regeneration in murine sepsis is dependent on regulatory protein levels.

Sepsis is a poorly understood syndrome. Therefore, we examined the mechanisms underlying failed regeneration in sham-operated (SO), mildly septic (cecal ligation and single puncture [CLP]), and severely septic (cecal ligation with two punctures [2CLP]) C57Bl6 mice. Relative to no operation (T0) or SO, CLP, but not 2CLP, increased the number of cells staining for proliferating cell nuclear antigen, a marker for cell division.

Protection against sepsis-induced lung injury by selective inhibition of protein kinase C-δ (δ-PKC).

Inflammation and proinflammatory mediators are activators of δ-PKC. In vitro, δ-PKC regulates proinflammatory signaling in neutrophils and endothelial and epithelial cells, cells that can contribute to lung tissue damage associated with inflammation. In this study, a specific δ-PKC TAT peptide inhibitor was used to test the hypothesis that inhibition of δ-PKC would attenuate lung injury in an animal model of ARDS.

Failed interleukin-6 signal transduction in murine sepsis: attenuation of hepatic glycoprotein 130 phosphorylation.

Objective: Sepsis impairs the activation of the interleukin (IL)-6 dependent transcription factor signal transducer and activator of transcription (STAT)-3. However, the molecular basis for depressed functionality has not been characterized. In this study, we test the hypothesis that altered signal transduction results from a change in the activation state of one or more of the components of the intracellular IL-6-linked pathway.

Enhanced expression of 70-kilodalton heat shock protein limits cell division in a sepsis-induced model of acute respiratory distress syndrome.

Objective: Fibrotic changes are initiated early in acute respiratory distress syndrome. This may involve overproliferation of alveolar type II cells. In an animal model of acute respiratory distress syndrome, we have shown that the administration of an adenoviral vector overexpressing the 70-kd heat shock protein (AdHSP) limited pathophysiological changes.

Enhanced heat shock protein 70 expression alters proteasomal degradation of IkappaB kinase in experimental acute respiratory distress syndrome.

Objectives: Acute respiratory distress syndrome is a common and highly lethal inflammatory lung syndrome. We previously have shown that an adenoviral vector expressing the heat shock protein (Hsp)70 (AdHSP) protects against experimental sepsis-induced acute respiratory distress syndrome in part by limiting neutrophil accumulation in the lung. Neutrophil accumulation and activation is modulated, in part, by the nuclear factor-kappaB (NF-kappaB) signal transduction pathway.

IL-6 modulates sepsis-induced decreases in transcription of hepatic organic anion and bile acid transporters.

Sepsis, a lethal inflammatory syndrome, is characterized by organ system dysfunction. In the liver, we have observed decreased expression of genes encoding proteins modulating key processes. These include organic anion and bile acid transport.

Sepsis-induced cholestasis, steatosis, hepatocellular injury, and impaired hepatocellular regeneration are enhanced in interleukin-6 -/- mice.

Objective: Hepatic dysfunction is an important but poorly understood component of sepsis. In severe sepsis, liver dysfunction is characterized by cholestasis, steatosis, hepatocellular injury, impaired regeneration, a decreased response to the cytokine interleukin-6, and high mortality. To determine whether loss of interleukin-6 activity caused hepatic dysfunction and mortality, we induced sepsis in wild-type (interleukin-6 +/+) and interleukin-6 knockout (interleukin-6 -/-) mice.

Competitive and noncompetitive inhibition of myocardial cytochrome C oxidase in sepsis.

Sepsis is the most common cause of death in intensive care units worldwide. The basic pathophysiologic defect in sepsis, causing functional abnormalities in many organ systems, remains elusive. One potential cause is disruption of oxidative phosphorylation in mitochondria.

Transcription factors C/EBP-alpha and HNF-1alpha are associated with decreased expression of liver-specific genes in sepsis.

Previous studies have demonstrated sepsis-specific changes in the transcription of key hepatic genes. However, the role of hepatic transcription factors in sepsis-associated organ dysfunction has not been well established. We hypothesize that the binding activities of C/EBPalpha and beta, HNF-1alpha, and HNF-3 transiently decrease during mild sepsis but persistently decrease after fulminant sepsis, and that the decrease in this binding activity correlates in time and severity with previously described decreases in the transcription of key hepatic genes.

Adenoviral transfer of HSP-70 into pulmonary epithelium ameliorates experimental acute respiratory distress syndrome.

The acute respiratory distress syndrome (ARDS) provokes three pathologic processes: unchecked inflammation, interstitial/alveolar protein accumulation, and destruction of pulmonary epithelial cells. The highly conserved heat shock protein HSP-70 can limit all three responses but is not appropriately expressed in the lungs after cecal ligation and double puncture (2CLP), a clinically relevant model of ARDS. We hypothesize that restoring expression of HSP-70 using adenovirus-mediated gene therapy will limit pulmonary pathology following 2CLP.