Spravato and other drugs with consciousness-altering effects show significant promise for treating various mental health disorders. However, the effects of these treatments necessitate a substantial degree of patient monitoring which can be burdensome to healthcare providers and may make these treatments less accessible for prospective patients. Continuous passive monitoring via digital devices may be useful in reducing this burden.
View Article and Find Full Text PDFActivation of the NLRP3 inflammasome induces maturation of IL-1β and IL-18, both validated targets for treating acute and chronic inflammatory diseases. Here, we demonstrate that OLT1177, an orally active β-sulfonyl nitrile molecule, inhibits activation of the NLRP3 inflammasome. In vitro, nanomolar concentrations of OLT1177 reduced IL-1β and IL-18 release following canonical and noncanonical NLRP3 inflammasome activation.
View Article and Find Full Text PDFObjective: To determine the safety and efficacy of propranolol given for 1 year on cardiac function, resting energy expenditure, and body composition in a prospective, randomized, single-center, controlled study in pediatric patients with large burns.
Background: Severe burns trigger a hypermetabolic response that persists for up to 2 years postburn. Propranolol given for 1 month postburn blunts this response.
Background: Recovery from a massive burn is characterized by catabolic and hypermetabolic responses that persist up to 2 years and impair rehabilitation and reintegration. The objective of this study was to determine the effects of long-term treatment with recombinant human growth hormone (rhGH) on growth, hypermetabolism, body composition, bone metabolism, cardiac work, and scarring in a large prospective randomized single-center controlled clinical trial in pediatric patients with massive burns.
Patients And Methods: A total of 205 pediatric patients with massive burns over 40% total body surface area were prospectively enrolled between 1998 and 2007 (clinicaltrials.
Introduction: Recent evidence suggests that female severely burned children have higher endogenous anabolic hormone levels and a shorter ICU stay compared with males. The purpose of this study was to analyze the influence of age and gender on resting energy expenditure (REE) in severely burned children from acute hospitalization through 12 months postburn.
Methods: A total of 100 pediatric patients with > 40% total body surface area (TBSA) burn were enrolled in a prospective study and followed by indirect calorimetry measurements.
Objective: To study the efficacy of growth hormone given to severely burned children from discharge to 12 months after burn and for 12 months after the drug was discontinued.
Summary Background Data: We have previously shown that low-dose recombinant human growth hormone (rhGH), given to children after a severe thermal injury, successfully improved lean muscle mass, bone mineral content, and growth. The aim of the present study was to investigate long-term functional improvements after treatment.
Background: Major trauma and burns are associated with whole body catabolism which can persist for 1 or more years after injury. This study investigates body composition in massively burned children for up to 2 years.
Methods: Twenty-five pediatric patients with greater than 40% total body surface area burns were studied.
Objective: The objective of this study was to test the hypothesis that hepatomegaly in burned children can be attenuated or reversed by blocking lipolysis and reducing free fatty acids delivered to the liver.
Summary Background Data: Accelerated lipolysis in severely burned children has been shown to play an important role in the accumulation of hepatic TGs. Severely burned children who survive 10 days or more after injury commonly have enlarged livers often twice or more normal size for their sex, age, and weight.
Hepatomegaly is a common postmortem observation in severely burned children, with the liver often tripling in size when compared with normal livers for age, weight, and sex. Lesions identified at autopsy include deposition of large and small fat droplets in the hepatocyte, congestion, centrilobular necrosis, and cholestasis. The present study was designed to identify the primary causes of hepatomegaly in severely burned children postmortem.
View Article and Find Full Text PDFObjective: When given to children for 1 year after a severe burn, oxandrolone significantly improves lean body mass, bone mineral content, and muscle strength. The beneficial effects of oxandrolone on height and weight were observed 1 year after treatment was discontinued. To study the efficacy of oxandrolone in severely burned children for 12 months after burn and 12 months after the drug was discontinued.
View Article and Find Full Text PDFIntroduction: Cutaneous wounds that involve loss of tissue heal through a complex process of generating granulation tissue to initially cover the wound, followed by epithelialization, and contraction. Normal healing requires a delicate balance between cellular, matrix, and vascularity build up and breakdown. Defects in the regulation of this balance can alter normal scar formation through fibroblastic hyperproliferation, which is characteristic of hypertrophic scar formation.
View Article and Find Full Text PDFSeveral studies have noted gender differences in adult mortality related to thermal injury, however, little is published on gender-related outcomes of burn patients 17 years of age or less. The aim of this study was to evaluate the relationships between mortality, gender, prepubertal and during puberty, ethnic origin, and age, with or without identified sepsis in severely burned children. Seven hundred forty-seven children admitted to our burn hospital from March 1985 to January 2005 with burns greater than 40% total body surface area were studied.
View Article and Find Full Text PDFObjective: Protein degradation, negative nitrogen balance and compromised structure of essential organs have been associated with resistance and decreased production of anabolic hormones. In turn, increased levels of anabolic hormones are associated with improved survival. The aims of the present study were to determine the pattern of anabolic hormones, resting energy expenditure and cytokines in severely thermally injured pediatric patients and to compare these parameters in female and male patients.
View Article and Find Full Text PDFObjective: The purpose of this study was to identify gene-expression changes in leg muscle for up to 24 months after a severe thermal injury.
Summary Background Data: Hypermetabolism associated with severe burns was thought to cease with wound healing and closure. It has been recently shown that hypermetabolism does not completely resolve after healing, and muscle catabolism continues after hospital discharge; however, just how long after discharge has not been established.
Background: Thermal injury is associated with a pronounced catabolic response in skeletal muscle. This study identifies gene expression changes in skeletal muscle of thermally injured girls and boys using high-density oligonucleotide arrays.
Methods: Six burned children with a mean age of 8.
The hypercatabolism after massive pediatric burns has been effectively treated with recombinant human growth hormone, an anabolic agent that stimulates protein synthesis and abrogates growth arrest. While experimental studies have shown increased potential for fibrosis induced by growth hormone therapy, adverse effects on human scars have not been investigated. Our aim was to evaluate hypertrophic scar formation in 62 patients randomized to receive injections of 0.
View Article and Find Full Text PDFHypothesis: The acute phase response is a cascade of events contributing to hypermetabolism and substrate catabolism. It was believed to persist for only a short time after injury. There is now evidence that systemic catabolism and hypermetabolism associated with thermal injury persevere for a long time.
View Article and Find Full Text PDFThe structural rearrangement of collagen fibres in hypertrophic scar causes abnormal contracture, low tensile strength, and raised scars, which cause functional impairment and disfigurement. It is hypothesized that changes in the genes of cytokines, extracellular matrix proteins, and proteins regulating programmed cell death are related to hypertrophic scar formation. To test this hypothesis, fibroblasts were cultured from hypertrophic scars and their response to interleukin-6 (IL-6) stimulation was studied by defining their gene expression profiles.
View Article and Find Full Text PDFThe liver plays an important role in a severe thermal injury by modulating immune function, inflammatory processes and the acute phase response, which are an orchestrated attempt to restore homeostasis. Using high-density oligonucleotide arrays, we examined the gene expression profile in the livers of rats between 2 and 240 h after a 40% total body surface area (TBSA) burn. Alterations in gene expression unique to a thermal injury were identified.
View Article and Find Full Text PDFBackground: Pulmonary failure has emerged as one of the leading causes of mortality in burned children due, in part, to the success in reducing the incidence of sepsis, early surgery and fluid resuscitation, and new advances in nutritional support. To evaluate the effect of pulmonary injury, age, gender, race, and burn size on mortality, the records of 3179 burned children admitted to our burn center from 1985 to 2001 were reviewed. In this population, 1246 were admitted within 14 days of injury with burns greater than 20% of their total body surface area (TBSA).
View Article and Find Full Text PDFIn this study, we investigated the effect of inflammatory cytokines on matrix metalloproteinase (MMP-1) and TIMP-1 production in human dermal fibroblasts, which play a pivotal role in wound healing, ranging from the synthesis and remodeling of extracellular matrix (ECM) to the synthesis of growth factors. The balance of MMPs and TIMPs is crucial in directing successful wound repair. Human adult dermal fibroblasts were seeded in six well plates (7.
View Article and Find Full Text PDFAm J Physiol Endocrinol Metab
October 2003
Propranolol, a nonselective beta-blocker, has been shown effective in hypermetabolic burn patients by decreasing cardiac work, protein catabolism, and lipolysis. This study investigates the effect of propranolol on gene and protein expression changes in skeletal muscle of burned children by use of high-density oligonucleotide arrays to establish the genetic profiles and stable isotope technique to quantitate protein synthesis. Thirty-seven children (mean age 9.
View Article and Find Full Text PDFWound Repair Regen
December 2003
Severe burns cause not only skin injury but several marked systemic derangements. During wound healing, matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases play an important role in tissue regeneration and remodeling processes. Therefore, in the present study, we determined the serum levels of MMPs and tissue inhibitor of metalloproteinase-1 in burn patients over time.
View Article and Find Full Text PDFThyroxine (T4), Tri-iodothyronine (T3), and total serum protein levels are reduced in severely burned children. T4 and T3 are carried on serum transport proteins via thyroid hormone-binding sites (THBS). Treatment of bums with recombinant human growth hormone (rhGH) increases albumin (Alb) and prealbumin (PreAlb), which bind nearly 30% of circulating T4 and T3.
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