Factors associated with an extended length of stay in the pediatric burn patient.

BACKGROUND: The Center for Medicaid and Medicare Services predicts the length of stay for pediatric burn patients based on several variables. However, many patients exceed their anticipated length. This study looks to identify aspects of patient presentation, wound characteristics, treatment, and discharge that are associated with a longer-than-predicted length of stay to identify strategies to safely reduce it. METHODS: We conducted a retrospective chart review of 535 pediatric burn patients admitted to our academic hospital from January 2018 to December 2020. 405 patients met inclusion criteria. Data were collected and analyzed. RESULTS: Average patient age was 3.36 years. 72.3% were treated for scald burns. Average length of stay was 13.5 days. 20.5% (n = 83) of patients exceeded their predicted length of stay. In comparing patients who exceeded their predicted length of stay to those who did not, the former had significant differences in burn causes, percent total body surface area burned (12.80% vs 4.24% [P = .000]), and body areas involved. Patients who exceeded length of stay had a higher incidence of endotracheal intubation (15.7% vs 1.3%), surgical intervention (85.5% vs 29.2%), need for tube-feeding (48.2% vs 4.3%), and intensive care unit admissions (22.9% vs 2.2% [P = .00 all]). They also averaged more operations, autografting (31.3% vs 1.6% [P = .00]), total operating room time (250 vs 31 minutes [P = .00]), and time to the first operation (2.32 vs 1.64 days [P = .00]). Tube-feeding averaged 9.52 vs 0.72 days (P = .00) extending patient stay after wound stability (43.9% vs 4.3% [P = .00]). These patients also required more discharge planning, with higher rates of Child Protective Services involvement (39.8% vs 10.9% [P = .00]), services consulted (1.06 vs 0.24 [P = .00]), and discharges to inpatient rehabilitation (8.6% vs 0.6% [P = .00]). 89.6% of all patients followed up in clinic. CONCLUSIONS: Twenty percent of pediatric burn patients had a longer length of stay than predicted by the Center for Medicaid and Medicare Services. Many factors were strongly associated with a longer-than-predicted length of stay. Identifying these early on might help reduce length of stay and meet the targets of the Center for Medicaid and Medicare Services.

Weight-based vs body surface area-based fluid resuscitation predictions in pediatric burn patients.

Treatment for pediatric burns includes fluid resuscitation with formulas estimating fluid requirements based on weight and/or body surface area (BSA) with percent total body surface area burn (%TBSA burn). This study evaluates the risk of complications using weight-based resuscitation in children following burn injuries and compares fluid estimates with those that incorporate BSA. A retrospective review was conducted on 110 children admitted to an ABA-verified urban pediatric burn center over 12 years. Patients had ≥ 15% TBSA burn and were resuscitated with the weight-based Parkland formula. BSA-based Galveston and BSA-incorporated Cincinnati formula predictions were calculated. Complications were collected throughout hospital stay. Patients were classified into weight groups based on percentile. This study included 11 underweight, 60 normal weight, 18 overweight, and 21 obese children. Total fluid administered was higher as percentile increased; however, overweight children received more fluid than the obese (p = 0.023). The Galveston formula underpredicted fluid given over the first 24 h post-injury (p = 0.042); the Parkland and Cincinnati formula predictions did not significantly differ from fluids given. Further research is needed to determine the value of weight-based vs BSA-based or incorporated formulas in reducing risk of complications.

Development of a Lensless Radiomicroscope for Cellular-Resolution Radionuclide Imaging.

The action of radiopharmaceuticals takes place at the level of cells. However, existing radionuclide assays can only measure uptake in bulk or in small populations of single cells. This potentially hinders the development of effective radiopharmaceuticals for disease detection, staging, and treatment. Methods: We have developed a new imaging modality, the lensless radiomicroscope (LRM), for in vitro, cellular-resolution imaging of ß- and α-emitting radionuclides. The palm-sized instrument is constructed from off-the-shelf parts for a total cost of less than $100, about 500 times less than the radioluminescence microscope, its closest equivalent. The instrument images radiopharmaceuticals by direct detection of ionizing charged particles via a consumer-grade complementary metal-oxide semiconductor detector. Results: The LRM can simultaneously image more than 5,000 cells within its 1 cm2 field of view, a 100-times increase over state-of-the-art technology. It has spatial resolution of 5 µm for brightfield imaging and 30 µm for 18F positron imaging. We used the LRM to quantify 18F-FDG uptake in MDA-MB-231 breast cancer cells 72 h after radiation treatment. Cells receiving 3 Gy were 3 times larger (mean = 3,116 µm2) than their untreated counterparts (mean = 940 µm2) but had 2 times less 18F-FDG per area (mean = 217 Bq/mm2), a finding in agreement with the clinical use of this tracer to monitor response. Additionally, the LRM was used to dynamically image the uptake of 18F-FDG by live cancer cells, and thus measure their avidity for glucose. Conclusion: The LRM is a high-resolution, large-field-of-view, and cost-effective approach to image radiotracer uptake with single-cell resolution in vitro.

Defining Benchmarks in Pediatric Burn Care: Inception of the Pediatric Injury Quality Improvement Collaborative.

Pediatric burn care is highly variable nationwide. Standardized quality and performance benchmarks are needed for guiding performance improvement within pediatric burn centers. A network of pediatric burn centers was established to develop and evaluate pediatric-specific best practices. A multi-disciplinary team including pediatric surgeons, nurses, advanced practice providers, pediatric intensivists, rehabilitation staff, and child psychologists from five pediatric burn centers established a collaborative to share and compare performance improvement data, evaluate outcomes, and exchange best care practices. In December 2016, the Pediatric Injury Quality Improvement Collaborative (PIQIC) was established. PIQIC members chose quality improvement indicators, drafted and approved a memorandum of understanding (MOU), data use agreement (DUA) and charter, formalized the multidisciplinary membership, and established a steering committee. Since inception, PIQIC has conducted monthly teleconferences and biannual in-person or virtual group meetings. A centralized data repository has been established where data is collated and analyzed for benchmarking in a blinded fashion. PIQIC has shown the feasibility of multi-institutional data collection, implementation of performance improvement metrics, publication of research, and enhancement of aggregate and institution-specific pediatric burn care.

A Retrospective Study of Touchless Spray for Pediatric Perineal Burns Treatment.

Silver-based topical treatments have seen widespread use for the management of burns due to silver's antimicrobial activity. Recent studies suggest that silver nanoparticles could negatively affect healing time due to their toxic effect on keratinocytes and fibroblasts at higher concentrations. Zinc oxide antimicrobial activity has been demonstrated in vitro, and results from animal studies are promising for burn management. At our ABA-verified pediatric burn center, the use of silver sulfadiazine cream ("Silvadene") has been slowly replaced by a zinc oxide/dimethicone spray-on solution ("Touchless Spray"). The dimethicone allows the spray to be occlusive without interfering with clothing, yet easily removed as opposed to Silvadene cream which requires wound scrubbing to remove and replace; potentially improving patient adherence with at-home treatments. This is the first study of zinc oxide's efficacy as a burn wound management agent in humans. We sought to compare the efficacy of silver sulfadiazine and that of zinc oxide/dimethicone to determine whether zinc oxide/dimethicone, in its easy-to-use form, is a viable alternative to silver sulfadiazine. We conducted a retrospective review of the electronic medical records of all patients treated for perineal, genital, perianal, suprapubic, or buttocks burn wounds at a large pediatric-verified burn center from January 1, 2014 to October 28, 2019. Only patients with superficial second-degree scald burns that arrived at our institution less than 24 hours after injury were included. Of a total 52 patients identified, 27 patients received silver sulfadiazine while 25 received zinc oxide/dimethicone. After initial evaluation and treatment by the burn team, all patients were followed up at our weekly burn clinic until complete healing was achieved. We retrospectively extracted demographic data, wound size, depth, and location, management strategies, time to complete healing, and incidence of infectious and noninfectious complications. The control group contained patients with total body surface area burns significantly greater than the zinc oxide/dimethicone group likely due to selective treatment when zinc oxide/dimethicone was first introduced at our facility. Time to healing was significantly lower in the zinc oxide/dimethicone intervention group (12.16 ± 8.644 days) than the silver sulfadiazine control group (16.89 ± 11.342 days). No infections were observed. Limitations include the relatively small sample sizes and differences in the size of burn wounds that confounded our results and likely negatively affected healing time in the control group. The zinc oxide/dimethicone group had a significantly lower healing time than the silver sulfadiazine group in the treatment of pediatric burns to the perineum, genitalia, suprapubis, and buttocks. Zinc oxide/dimethicone may prove to be a useful tool for treating burn wounds, and further study is needed to determine its efficacy and safety.

Outcomes of Early Surgical vs Nonsurgical Management of Pediatric Hand Friction Injuries Caused by Treadmills.

Pediatric hand friction injuries caused by running treadmills are ever more prevalent due to the increasing presence of home exercise equipment. These and other related injuries have received recent attention in the media, leading to mass product recalls in some cases. These friction injuries are similar to deep thermal burns, and these patients are usually cared for in the pediatric burn unit at our institution. We sought to describe our recent experience managing 22 patients with these injuries. Patients were queried from our urban pediatric burn center database. After Institutional Review Board approval, a retrospective chart review of all patients admitted for a treadmill-related hand injury over a 5-year period was performed. Data collected included patient demographics, initial treatment methods (surgical vs nonoperative), type of dressing used, hospital length of stay (LOS), and compliance with follow-up. We collected patient-centered outcomes included the time to healing and the need for subsequent surgical and/or nonsurgical interventions to treat the sequelae of these injuries. Our center treated 22 hand friction injuries caused by treadmills over the 5-year period. Five patients (23%) underwent early surgical intervention (<30 days from injury), with a median time from injury of 7 days (interquartile range 1.75-13.5). This cohort required additional interventions to treat postoperative sequelae with 2 (40%) requiring additional surgery and 3 (60%) managed nonsurgically. Of the 17 (77%) who were initially treated nonoperatively, 5 (29%) healed completely with dressing changes only and required no further treatment. Eleven (65%) had injury-related sequelae and were managed successfully with nonsurgical interventions. Only 1 patient (6%) required scar modification by Z-plasty. Average LOS was 14 hours and the median number of weekly follow-up visits was 4 until complete healing. Given the excellent outcomes observed in patients treated without acute surgical intervention in this case series, nonoperative management appears to be feasible, safe, and may reduce the need for operative intervention. These injuries, although small, are deep and require a prolonged period of dressing changes and aggressive therapy including posthealing time commitment to scar management in order to achieve best outcomes. Our study supports the need for increased community awareness of this type of injury.

Juvenile Xanthogranuloma of the Pancreas in a Pediatric Patient Mimicking Pancreatic Neoplasm With High CA 19-9: Case Report and Literature Review.

Juvenile xanthogranuloma (JXG) is a rare, non-Langerhans cell histiocytosis. It is usually a benign and self-limiting condition. The most common sites are skin and soft tissue. Pancreatic involvement is extremely rare. We present an unusual case of a 13-month-old female child with JXG of the pancreas and elevated cancer antigen 19-9. JXG should always be considered as a differential diagnosis for pediatric patients presenting with a pancreatic mass, solid and/or cystic in nature. Therefore, avoiding unnecessary invasive diagnostic procedures.

Length of Stay per Total Body Surface Area Burn Relative to Mechanism: A Pediatric Injury Quality Improvement Collaborative Study.

Studies on length of stay (LOS) per total body surface area (TBSA) burn in pediatric patients are often limited to single institutions and are grouped in ranges of TBSA burn which lacks specific detail to counsel patients and families. A LOS to TBSA burn ratio of 1 has been widely accepted but not validated with multi-institution data. The objective of this study is to describe the current relationship of LOS per TBSA burn and LOS per TBSA burn relative to burn mechanism with the use of multi-institutional data. Data from the Pediatric Injury Quality Improvement Collaborative (PIQIC) were obtained for patients across five pediatric burn centers from July 2018 to September 2020. LOS per TBSA burn ratios were calculated. Descriptive statistics and generalized linear regression which modeled characteristics associated with LOS per TBSA ratio are described. Among the 1267 pediatric burn patients, the most common mechanism was scald (64%), followed by contact (17%) and flame (13%). The average LOS/TBSA burn ratio across all cases was 1.2 (SD = 2.1). In adjusted models, scald burns and chemical burns had similar LOS/TBSA burn ratios of 0.8 and 0.9, respectively, whereas all other burns had a significantly higher LOS/TBSA burn ratio (p<0.0001). LOS/TBSA burn ratios were similar across races, although Hispanics had a slightly higher ratio at 1.4 days. These data establish a multi-institution LOS per TBSA ratio across PIQIC centers and demonstrate a significant variation in the LOS per TBSA burn relative to the burn mechanism sustained.

Variation in acute fluid resuscitation among pediatric burn centers.

BACKGROUND: Accurate resuscitation of pediatric patients with large thermal injury is critical to achieving optimal outcomes. The goal of this project was to describe the degree of variability in resuscitation guidelines among pediatric burn centers and the impact on fluid estimates. METHODS: Five pediatric burn centers in the Pediatric Injury Quality Improvement Collaborative (PIQIC) contributed data from patients with ≥15% total body surface area (TBSA) burns treated from 2014 to 2018. Each center's resuscitation guidelines and guidelines from the American Burn Association were used to calculate estimated 24-h fluid requirements and compare these values to the actual fluid received. RESULTS: Differences in the TBSA burn at which fluid resuscitation was initiated, coefficients related to the Parkland formula, criteria to initiate dextrose containing fluids, and urine output goals were observed. Three of the five centers' resuscitation guidelines produced statistically significant lower mean fluid estimates when compared with the actual mean fluid received for all patients across centers (4.53 versus 6.35ml/kg/% TBSA, p<0.001), (4.90 versus 6.35ml/kg/TBSA, p=0.002) and (3.38 versus 6.35ml/kg/TBSA, p<0.0001). CONCLUSIONS: This variation in practice patterns led to statistically significant differences in fluid estimates. One center chose to modify its resuscitation guidelines at the conclusion of this study.

Sink bathing burns: A unique opportunity for an injury prevention initiative.

Sink-bathing is common practice among parents. However, this puts infants and young children at unrecognized risk for burn injuries. As the only verified pediatric burn center in a large urban area, we treat burn patients from a large variation in socioeconomic status. This provides us a unique opportunity to examine sink-burn injury patterns, circumstances surrounding these burns, identify areas with high incidence and put in place an injury prevention outreach initiative. This retrospective study included patients treated for sink-bathing burns at our burn center in an 8.5-year period. Analysis of 71 patients revealed infants under one year of age are most commonly afflicted. Additionally, that families of low-socioeconomic means are disproportionately affected. Understanding the different circumstances surrounding sink-bathing burns allows us to be more specific in our community education efforts and efficiently guide our resources.

Radioluminescence in biomedicine: physics, applications, and models.

The electromagnetic spectrum contains different frequency bands useful for medical imaging and therapy. Short wavelengths (ionizing radiation) are commonly used for radiological and radionuclide imaging and for cancer radiation therapy. Intermediate wavelengths (optical radiation) are useful for more localized imaging and for photodynamic therapy (PDT). Finally, longer wavelengths are the basis for magnetic resonance imaging and for hyperthermia treatments. Recently, there has been a surge of interest for new biomedical methods that synergize optical and ionizing radiation by exploiting the ability of ionizing radiation to stimulate optical emissions. These physical phenomena, together known as radioluminescence, are being used for applications as diverse as radionuclide imaging, radiation therapy monitoring, phototherapy, and nanoparticle-based molecular imaging. This review provides a comprehensive treatment of the physics of radioluminescence and includes simple analytical models to estimate the luminescence yield of scintillators and nanoscintillators, Cherenkov radiation, air fluorescence, and biologically endogenous radioluminescence. Examples of methods that use radioluminescence for diagnostic or therapeutic applications are reviewed and analyzed in light of these quantitative physical models of radioluminescence.

Theoretical investigation of ultrasound-modulated Cerenkov luminescence imaging for higher-resolution imaging in turbid media.

Cerenkov luminescence imaging (CLI) is an optical technique for imaging radiolabeled molecules in vivo. It has demonstrated utility in both the clinical and preclinical settings and can serve as a substitute for nuclear imaging instrumentation in some cases. However, optical scattering fundamentally limits the resolution and depth of imaging that can be achieved with this modality. In this Letter, we report the numerical results that support the potential for ultrasound-modulated Cerenkov luminescence imaging (USCLI), a new imaging modality that can mitigate optical scattering. The technique uses an acoustic field to modulate the refractive index of the medium and, thus, the intensity of Cerenkov luminescence in a spatially precise manner. This mechanism of contrast has not been reported previously. For a physiologically compatible ultrasound peak pressure of 1 MPa, ∼0.1% of the Cerenkov signal can be modulated. Furthermore, our simulations show that USCLI can overcome the scattering limit of resolution for CLI and provide higher-resolution imaging. For an F18 point source centered in a 1 cm3 simulated tissue phantom with a scattering coefficient of µs'=10 cm-1, <2 mm full width at half-maximum lateral spatial resolution is possible, a resolution three times finer than the same phantom imaged with CLI.

Analysis of Electrocardiograms Associated with Pediatric Electrical Burns.

The purpose of this study was to examine the utility of electrocardiograms (EKGs) for low-risk, low-voltage pediatric electrical burn victims. A retrospective chart review was conducted on 86 pediatric patients who presented to the children's hospital between 2000 and 2015 after sustaining electrical burns. Variables included source and estimated voltage, extent of injuries, length of stay, high risk factors, and EKG results. High risk factors included estimated voltage > 1000 V, lightning, tetany, symptoms, loss of consciousness, or seizures. Statistical analyses were conducted. Average age was 5 years. Of those who sustained burns, 84.5% (n = 71/84) had second-degree burns ≤ 1% TBSA or less. Eleven patients had high risk factors, 12.9% (n = 11/85) and most had length of stay < 3 days (91.8%; n = 78/85). Majority sustained burns from low-voltage (< 300 V) household electrical outlets, cords, or light bulb sockets (90.4%; n = 75/83). Among patients with available EKGs, 12 had arrhythmias on initial EKG (i.e., low right atrial rhythm, t-wave inversions, sinus tachycardia, bundle branch block; 20.7%; n = 12/58). All were transient and nonfatal. The data suggest that low estimated voltage (< 300 V) electrical injuries were associated with negative EKGs; however, due to the low rate of arrhythmias, a Fisher's exact test did not show significance, P = 0.09 (P > 0.05). Preliminary data suggest that most pediatric electrical burns are due to low voltage (< 300 V) household sources. Few have high risk factors or arrhythmias that were transient and nonfatal. These data suggest that low-risk, asymptomatic, low-voltage pediatric electrical burns may not require an initial screening EKG.

Quantitative assessment of Cerenkov luminescence for radioguided brain tumor resection surgery.

Cerenkov luminescence imaging (CLI) is a developing imaging modality that detects radiolabeled molecules via visible light emitted during the radioactive decay process. We used a Monte Carlo based computer simulation to quantitatively investigate CLI compared to direct detection of the ionizing radiation itself as an intraoperative imaging tool for assessment of brain tumor margins. Our brain tumor model consisted of a 1 mm spherical tumor remnant embedded up to 5 mm in depth below the surface of normal brain tissue. Tumor to background contrast ranging from 2:1 to 10:1 were considered. We quantified all decay signals (e±, gamma photon, Cerenkov photons) reaching the brain volume surface. CLI proved to be the most sensitive method for detecting the tumor volume in both imaging and non-imaging strategies as assessed by contrast-to-noise ratio and by receiver operating characteristic output of a channelized Hotelling observer.

Extracorporeal membrane oxygenation outcomes in children with hemophagocytic lymphohistiocytosis.

INTRODUCTION: Pediatric patients with hemophagocytic lymphohistiocytosis (HLH) may develop refractory respiratory or cardiac failure that warrants consideration for extracorporeal membrane oxygenation (ECMO) support. The purposes of this study were to describe the use and outcomes of ECMO in pediatric HLH patients, to identify risk factors for hospital mortality and to compare their ECMO use and outcomes to the ECMO population as a whole. METHODS: Pediatric patients (⩽ 18 years) with a diagnosis of HLH in the Extracorporeal Life Support Organization (ELSO) Registry were included. RESULTS: Between 1983 and 2014, data for 30 children with HLH were available in the ELSO registry and all were included in this study. All cases occurred in the last decade. Of the 30 HLH patients, 24 (80%) had a respiratory indication for ECMO and six (20%) had a cardiac indication (of which 4 were E-CPR and 2 cardiac failure). Of the 24 respiratory ECMO patients, 63% were placed on VA ECMO. Compared with all pediatric patients in the ELSO registry during the study period (n=17,007), HLH patients had worse hospital survival (non-HLH 59% vs HLH 30%, p=0.001). In pediatric HLH patients, no pre-ECMO risk factors for mortality were identified. The development of a hemorrhagic complication on ECMO was associated with decreased mortality (p=0.01). Comparing HLH patients with respiratory failure to patients with other immune compromised conditions, the overall survival rate is similar (HLH 38% vs. non-HLH immune compromised 31%, p=0.64). CONCLUSIONS: HLH is an uncommon indication for ECMO and these patients have increased mortality compared to the overall pediatric ECMO population. These data should be factored into decision-making when considering ECMO for pediatric HLH patients.

Different types of retinal inhibition have distinct neurotransmitter release properties.

Neurotransmitter release varies between neurons due to differences in presynaptic mechanisms such as Ca(2+) sensitivity and timing. Retinal rod bipolar cells respond to brief dim illumination with prolonged glutamate release that is tuned by the differential release of GABA and glycine from amacrine cells in the inner retina. To test if differences among types of GABA and glycine release are due to inherent amacrine cell release properties, we directly activated amacrine cell neurotransmitter release by electrical stimulation. We found that the timing of electrically evoked inhibitory currents was inherently slow and that the timecourse of inhibition from slowest to fastest was GABAC receptors > glycine receptors > GABAA receptors. Deconvolution analysis showed that the distinct timing was due to differences in prolonged GABA and glycine release from amacrine cells. The timecourses of slow glycine release and GABA release onto GABAC receptors were reduced by Ca(2+) buffering with EGTA-AM and BAPTA-AM, but faster GABA release on GABAA receptors was not, suggesting that release onto GABAA receptors is tightly coupled to Ca(2+). The differential timing of GABA release was detected from spiking amacrine cells and not nonspiking A17 amacrine cells that form a reciprocal synapse with rod bipolar cells. Our results indicate that release from amacrine cells is inherently asynchronous and that the source of nonreciprocal rod bipolar cell inhibition differs between GABA receptors. The slow, differential timecourse of inhibition may be a mechanism to match the prolonged rod bipolar cell glutamate release and provide a way to temporally tune information across retinal pathways.

Operative indications in recurrent ileocolic intussusception.

BACKGROUND: Air-contrast enema (ACE) is standard treatment for primary ileocolic intussusception. Management of recurrences is less clear. This study aimed to delineate appropriate therapy by quantifying the relationship between recurrence and need for bowel resection, pathologic lead points (PLP), and complication rates. METHODS: After IRB approval, a single institution review of patients with ileocolic intussusception from 1997 to 2013 was performed, noting recurrences, outcomes, and complications. Fisher's exact and t-tests were used. RESULTS: Of 716 intussusceptions, 666 were ileocecal. Forty-four underwent bowel resection, with 29 PLPs and 9 ischemia/perforation. Recurrence after ACE occurred in 96 (14%). Recurrence did not predict PLP (P=0.25). Recurrence (≥3) was associated with higher resection rate (P=0.03), but not ischemia/perforation (P=0.75). ACE-related complications occurred in 4 (0.5%) patients. Successful initial ACE had 98% negative predictive value for resection and PLP (e.g., after successful ACE, 2% had resections, 2% PLP). After failed initial ACE, 36% received resection, and 23% had PLP (P<0.001). CONCLUSIONS: Recurrence is associated with a greater risk of resection but not PLP or ACE-complication. Failed ACE is associated with increased risk for harboring PLP and receiving resection. ACE should be the standard treatment in recurrent intussusception, regardless of number of recurrences.

Slow changes in Ca2(+) cause prolonged release from GABAergic retinal amacrine cells.

The timing of neurotransmitter release from neurons can be modulated by many presynaptic mechanisms. The retina uses synaptic ribbons to mediate slow graded glutamate release from bipolar cells that carry photoreceptor inputs. However, many inhibitory amacrine cells, which modulate bipolar cell output, spike and do not have ribbons for graded release. Despite this, slow glutamate release from bipolar cells is modulated by slow GABAergic inputs that shorten the output of bipolar cells, changing the timing of visual signaling. The time course of light-evoked inhibition is slow due to a combination of receptor properties and prolonged neurotransmitter release. However, the light-evoked release of GABA requires activation of neurons upstream from the amacrine cells, so it is possible that prolonged release is due to slow amacrine cell activation, rather than slow inherent release properties of the amacrine cells. To test this idea, we directly activated primarily action potential-dependent amacrine cell inputs to bipolar cells with electrical stimulation. We found that the decay of GABAC receptor-mediated electrically evoked inhibitory currents was significantly longer than would be predicted by GABAC receptor kinetics, and GABA release, estimated by deconvolution analysis, was inherently slow. Release became more transient after increasing slow Ca(2+) buffering or blocking prolonged L-type Ca(2+) channels and Ca(2+) release from intracellular stores. Our results suggest that GABAergic amacrine cells have a prolonged buildup of Ca(2+) in their terminals that causes slow, asynchronous release. This could be a mechanism of matching the time course of amacrine cell inhibition to bipolar cell glutamate release.

Inhibition to retinal rod bipolar cells is regulated by light levels.

The retina responds to a wide range of light stimuli by adaptation of retinal signaling to background light intensity and the use of two different photoreceptors: rods that sense dim light and cones that sense bright light. Rods signal to rod bipolar cells that receive significant inhibition from amacrine cells in the dark, especially from a rod bipolar cell-activated GABAergic amacrine cell. This inhibition modulates the output of rod bipolar cells onto downstream neurons. However, it was not clear how the inhibition of rod bipolar cells changes when rod signaling is limited by an adapting background light and cone signaling becomes dominant. We found that both light-evoked and spontaneous rod bipolar cell inhibition significantly decrease with light adaptation. This suggests a global decrease in the activity of amacrine cells that provide input to rod bipolar cells with light adaptation. However, inhibition to rod bipolar cells is also limited by GABAergic connections between amacrine cells, which decrease GABAergic input to rod bipolar cells. When we removed this serial inhibition, the light-evoked inhibition to rod bipolar cells remained after light adaptation. These results suggest that decreased inhibition to rod bipolar cells after light adaptation is due to decreased rod pathway activity as well as an active increase in inhibition between amacrine cells. Together these serve to limit rod bipolar cell inhibition after light adaptation, when the rod pathway is inactive and modulation of the signal is not required. This suggests an efficiency mechanism in the retina to limit unnecessary signaling.