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Greenhalgh D.G.,Shriners Hospitals for Children Northern California | Greenhalgh D.G.,University of California at Davis
Journal of Burn Care and Research | Year: 2015

There is at least a temporary loss of skin pigmentation with all but first-degree burns. Commonly, pigment changes persist for months, and sometimes, permanent changes in skin color add to the ultimate change in appearance that commonly affects burn patients. There are many different treatment modalities for the treatment of pigment changes, but most of them have little scientific basis and often lead to disappointing results. The purpose of this review is to discuss the molecular and cellular mechanisms of skin pigmentation, mechanisms of repigmentation after burns, treatment options for dealing with pigmentation changes, and advice for dealing with the sun after burn injury. © 2014 by the American Burn Association.


Dixit N.,University of California at Davis | Wu D.J.,University of California at Davis | Belgacem Y.H.,Shriners Hospitals for Children Northern California | Borodinsky L.N.,Shriners Hospitals for Children Northern California | And 3 more authors.
Arthritis Research and Therapy | Year: 2014

Introduction: Bone erosion in inflammatory arthritis depends on the recruitment and activation of bone resorbing cells, the osteoclasts. Interleukin-23 (IL-23) has been primarily implicated in mediating inflammatory bone loss via the differentiation of Th17 receptor activator of nuclear factor κB ligand (RANKL)-producing cells. In this article, we describe a new role of IL-23 in activating the synthesis and production of leukotriene B4 (LTB4) in innate immune cells. Methods: We utilized whole blood-derived human peripheral blood mononuclear cells (PBMCs), differentiated them towards an osteoclast lineage and then performed immunofluorescence and cytochemical staining to detect the expression of LTB4-associated receptors and enzymes such as phospholipase A2, 5-lipoxygenase and leukotriene A4 hydrolase, as well as the presence of tartrate-resistant acid phosphatase (TRAP) and F-actin rings on fully mature osteoclasts. We used enzyme immunoassays to measure LTB4 levels in culture media derived from IL-23-treated human PBMCs. We used real-time calcium imaging to study the effect of leukotrienes and requirements of different calcium sources and signaling proteins in activating intracellular calcium flux using pharmacological inhibitors to phospholipase C (U73122), membrane calcium channels (2-APB) and phosphatidylinositol 3-kinase (Wortmannin) and utilized qPCR for gene expression analysis in macrophages and osteoclasts. Results: Our data show that LTB4 engagement of BLT1 and BLT2 receptors on osteoclast precursors leads to activation of phospholipase C and calcium release-activated channel-mediated intracellular calcium flux, which can activate further LTB4 autocrine production. IL-23-induced synthesis and secretion of LTB4 resulted in the upregulation of osteoclast-related genes NFATC1, MMP9, ACP5, CTSK and ITGB3 and the formation of giant, multinucleated TRAP+ cells capable of F-actin ring formation. These effects were dependent on Ca2+ signaling and were completely inhibited by BLT1/BLT2 and/or PLC and CRAC inhibitors. Conclusions: In conclusion, IL-23 can initiate osteoclast differentiation independently from the RANK-RANKL pathway by utilizing Ca2+ signaling and the LTB4 signaling cascade. © 2014 Dixit et al.. licensee BioMed Central Ltd.


Man A.J.,University of California at Davis | Davis H.E.,University of California at Davis | Itoh A.,University of California at Davis | Itoh A.,Shriners Hospitals for Children Northern California | And 2 more authors.
Tissue Engineering - Part A | Year: 2011

Fibrin is a promising matrix for use in promoting nerve repair given its natural occurrence in peripheral nerve injuries, and the biophysical properties of this matrix can be regulated to modulate tissue regeneration. In this study, we examined the effect of physical and mechanical properties of fibrin gels on dorsal root ganglia (DRG) neurite extension. Increases in fibrinogen concentration increased the number of fibrin strands, resulting in decreased pore size and increased stiffness. Neurite extension was reduced when DRG explants were cultured within fibrin gels of increasing fibrinogen concentrations (from 9.5 to 141mg/mL). The addition of NaCl also increased the number of fibrin strands, reducing fiber diameter and porosity, while increasing mechanical strength, and reductions in neurite extension correlated with increases in NaCl content. We determined that neurite extension within fibrin gels is dependent on fibrinolysis and is mediated by the secretion of serine proteases and matrix metalloproteinases by entrapped DRGs, as confirmed by culturing cells in the presence of inhibitors against these enzymes and real-time-polymerase chain reaction. Taken together, the results of this study provide new insight into the effect of fibrin gel biophysical properties on neurite extension and suggest new opportunities to improve the efficacy of these materials when used as nerve guidance conduits. © 2011, Mary Ann Liebert, Inc.


Rab G.T.,University of California at Davis | Rab G.T.,Shriners Hospitals for Children Northern California
Journal of Children's Orthopaedics | Year: 2010

Purpose: Oblique proximal tibial osteotomy is a useful option for correcting deformity associated with Blount's disease (tibia vara). Safe, adequate correction depends on technical issues that have evolved since the original description of the procedure. Methods: Retrospective review of surgical experience. Results: The refinement of osteotomy plane orientation, based on the distal rather than the proximal tibia, reduces the likelihood of procurvatum after surgery. The stability of the osteotomy is enhanced by an improved screw fixation technique. The risk of compartment syndrome is low if prophylactic partial fasciotomy is performed concurrently. Avoidance of spinal or regional block anesthesia minimizes the possibility of failure to detect post-operative compartment syndrome. Conclusions: Improvements in the technical execution of oblique proximal tibial osteotomy enhances the correction and predictability of the procedure. © The Author(s) 2009.


Greenhalgh D.G.,Shriners Hospitals for Children Northern California | Greenhalgh D.G.,University of California at Davis
Burns | Year: 2010

Introduction: There are valid concerns that burn shock resuscitation is inadequate; a tendency to over-resuscitate the patient seems to exist which may increase complications such as compartment syndrome. The purpose of this study was to survey members of the ISBI and ABA to determine current practices of burn resuscitation. Methods: A survey asking for practices of burn shock resuscitation was provided to all participants of a recent ABA meeting. Around the same time, the survey was sent to all members of the ISBI through the internet. The results of the 101 respondents (ABA - 59, ISBI - 42, approximately a 15% response rate) are described. Results: Surveys were returned from all the continents except Africa. Respondents included directors (48%), staff physicians (19%), nurses (23%) and others. Most programs admitted adults (87%) and children (75%) with a mean of 289 admissions per year. The cut off to initiate resuscitation was 15% TBSA and most preferred peripheral IVs (70%) and central lines (47.5%). The Parkland formula was preferred (69.3%) while others were used: Brooke - 6.9%, Galveston - 8.9%, Warden - 5.9%, and colloid 11.9%. Lactated Ringer's (LR) was the preferred solution (91.9%), followed by normal saline - 5%, hypertonic saline - 4%, albumin - 20.8%. FFP - 13.9%, and LR/NaHCO3 - 12.9%. Approximately half (49.5%) added colloid before 24 h. Urine output is the major indicator of success (94.9%) while 22.7% use other monitors. Most (88.8%) feel their protocols work well with 69.8% feel that it provides the right amount of fluid (24% - too much, 7% - too little). Despite this feeling, they still feel that they give more fluid than the formula in 55.1%, less than formula in 12.4% and the right amount in 32.6%. Approximately 1/3 use an oral resuscitation formula and 81.8% feel that an oral formula works for burns < 15% TBSA. Conclusion: Large variations exist in resuscitation protocols but the Parkland formula using LR is still the dominant method. Most feel that their resuscitation protocol works well. © 2009 Elsevier Ltd and ISBI.


Navickis R.J.,Hygeia | Greenhalgh D.G.,Shriners Hospitals for Children Northern California | Greenhalgh D.G.,University of California at Davis | Wilkes M.M.,Hygeia
Journal of Burn Care and Research | Year: 2016

Critical appraisal of outcomes after burn shock resuscitation with albumin has previously been restricted to small relatively old randomized trials, some with high risk of bias. Extensive recent data from nonrandomized studies assessing the use of albumin can potentially reduce bias and add precision. The objective of this meta-Analysis was to determine the effect of burn shock resuscitation with albumin on mortality and morbidity in adult patients. Randomized and nonrandomized controlled clinical studies evaluating mortality and morbidity in adult patients receiving albumin for burn shock resuscitation were identified by multiple methods, including computer database searches and examination of journal contents and reference lists. Extracted data were quantitatively combined by random-effects meta-Analysis. Four randomized and four nonrandomized studies with 688 total adult patients were included. Treatment effects did not differ significantly between the included randomized and nonrandomized studies. Albumin infusion during the first 24 hours showed no significant overall effect on mortality. However, significant statistical heterogeneity was present, which could be abolished by excluding two studies at high risk of bias. After those exclusions, albumin infusion was associated with reduced mortality. The pooled odds ratio was 0.34 with a 95% confidence interval of 0.19 to 0.58 (P <.001). Albumin administration was also accompanied by decreased occurrence of compartment syndrome (pooled odds ratio, 0.19; 95% confidence interval, 0.07-0.50; P <.001). This meta-Analysis suggests that albumin can improve outcomes of burn shock resuscitation. However, the scope and quality of current evidence are limited, and additional trials are needed.


Van Heest A.E.,University of Minnesota | Bagley A.,Shriners Hospitals for Children Northern California | Molitor F.,Shriners Hospitals for Children Northern California | James M.A.,Shriners Hospitals for Children Northern California
Journal of Bone and Joint Surgery - American Volume | Year: 2015

Background: For children with upper-extremity cerebral palsy (CP) who meet standard indications for tendon transfer surgery, we hypothesized that surgical treatment would result in greater functional improvement than treatment with botulinum toxin injections or regular, ongoing therapy. Methods: Thirty-nine children with upper-extremity CP, who were four to sixteen years of age and surgical candidates for the transfer of the flexor carpi ulnaris to the extensor carpi radialis brevis, pronator teres release, and extensor pollicis longus rerouting with adductor pollicis release, were prospectively assigned, either randomly (twenty-nine patients) or by patient/family preference (ten patients), to one of three treatment groups: surgical treatment (Group 1); botulinum toxin injections (Group 2); or regular, ongoing therapy (Group 3). Seven centers participated. Assessment measurements included active range of motion, pinch and grip strength, stereognosis, and scores as measured with eight additional functional or patient-oriented outcome instruments. Thirty-four patients (twenty-five randomized and nine from the patientpreference arm) were evaluated twelve months post-treatment as the study cohort. Results: For the primary outcome of the Shriners Hospital Upper Extremity Evaluation (SHUEE) dynamic positional analysis (DPA), significantly greater improvement was seen in Group 1 than in the other two groups (p < 0.001). Improvements in SHUEE DPA reflected improved supination and wrist extension during functional activities after surgical treatment. Group 1 showed more improvement in the Pediatric Quality of Life Inventory (PedsQL) CP module domain of movement and in the Canadian Occupational Performance Measure (COPM) score for satisfaction than Groups 2 and 3. Both Groups 1 and 3 showed more improvement in pinch strength than did Group 2. Conclusions: For children with upper-extremity CP who were candidates for standard tendon transfer, surgical treatment was demonstrated to provide greater improvement, of modest magnitude, than botulinum toxin injections or regular, ongoing therapy at twelve months of follow-up for the SHUEE DPA, the PedsQL CP module domain of movement, and COPM satisfaction. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.


Palmieri T.L.,Shriners Hospitals for Children Northern California
The journal of trauma and acute care surgery | Year: 2012

The purpose of this multicenter study was to evaluate the impact of hand burn injury in preschool children younger than 5 years on health-related quality of life, including both physical and psychosocial function, in the 5 years after burn injury. This prospective case series assessed children younger than 5 years admitted to four pediatric burn centers. Each child's family completed the American Burn Association/Shriners Hospitals for Children Burn Outcome Questionnaire (BOQ), a validated and reliable assessment tool, which measures the physical and psychosocial functioning of the child with burn injury ages 0 year to 5 years, at baseline, 3, 6, 12, 18, 24, 36, and 48 months after discharge. Multivariate models controlling for sociodemographic and clinical characteristics were developed, and recovery curves were generated for the time since burn using generalized estimating equations with random effects. A cohort of 438 patients was followed up prospectively. Mean (SD) patient age was 2.2 (1.2) years, mean (SD) total body surface area (TBSA) was 28% (22.4%), and 19% had inhalation injury. Children with hand burns had lower scores in most of the areas tested, with the most pronounced and significant differences were in fine motor function, gross motor function, and appearance. These findings applied to both small (<20% TBSA) and large (≥20% TBSA) burns. The most profound impact of hand burns was noted in fine and gross motor function during the 4 years of follow-up. Children with hand burns have significantly worse outcomes than do children with burns in other areas.


Chen Z.,Neurology 2G | Lerman J.,Shriners Hospitals for Children Northern California
Journal of Clinical Monitoring and Computing | Year: 2012

Objective: To demonstrate the usefulness of rectus femoris muscle MEPs monitoring in a paraparetic neuro-muscular scoliosis case. Methods: Multiple monitoring modalities including SEPs, MEPs and EMG were performed for an anterior and posterior correction surgery for a neuromuscular scoliosis patient with no motor and sensory function below the knees. Results: Bilateral tibial nerve SEPs were absent, and no MEPs were recordable from anterior tibialis and abductor hallucis muscles bilaterally at baseline. Robust MEPs were recorded on abductor pollicis brevis and rectus femoris muscles bilaterally. Spinal cord monitoring mainly relied on MEPs from bilateral rectus femoris muscles (RF-MEPs). Twice RF-MEPs were absent following deformity correction and returned after removal of both rods. The patient's remaining spinal cord function was preserved. Conclusions: Intraoperative neurophysiological monitoring should be used for neuromuscular scoliosis cases with paraparesis if proximal function, such as the rectus femoris muscle, exists. © Springer Science+Business Media, LLC 2011.


Smith W.D.,California State University, Sacramento | Bagley A.,Shriners Hospitals for Children Northern California
2010 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC'10 | Year: 2010

Children with cerebral palsy may have difficulty walking and may fall frequently, resulting in a decrease in their participation in school and community activities. It is desirable to assess the effectiveness of mobility therapies for these children on their functioning during everyday living. Over 50 hours of tri-axial accelerometer and digital video recordings from 35 children with cerebral palsy and 51 typically-developing children were analyzed to develop algorithms for automatic real-time processing of the accelerometer signals to monitor a child's level of activity and to detect falls. The present fall-detection algorithm has 100% specificity and a sensitivity of 100% for falls involving trunk rotation. Sensitivities for drops to the knees and to the bottom are 72% and 78%, respectively. The activity and fall-detection algorithms were implemented in a miniature, battery-powered microcontroller-based activity/fall monitor that the child wears in a small fanny pack during everyday living. The monitor continuously logs 1-min. activity levels and the occurrence and characteristics of each fall for two-week recording sessions. Pre-therapy and post-therapy recordings from these monitors will be used to assess the efficacies of alternative treatments for gait abnormalities. © 2010 IEEE.

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