Three-dimensional Spinal Canal Morphometric Analysis and Relevant Spinal Cord Occupational Ratios in Congenital Cervical Spinal Stenosis: A Classification Algorithm of the Stenosis Phenotypes and Data-driven Decompression Approach.

OBJECTIVES: No standardized magnetic resonance imaging (MRI) parameters have defined the 3-dimensional morphoanatomy and relevant spinal cord occupation ratios (occupation of spinal cord dimensions/similar dimensions within the spinal canal) in congenital cervical stenosis (CCS). METHODS: A retrospective, comparative analysis was conducted on 200 patients >18 years of age with myelopathy and CCS (mean age, 52.4 years) and 200 age-matched controls with no myelopathy or radiculopathy. The variables assessed from high resolution MRI included sagittal and axial spinal canal dimensions (MRI Torg-Pavlov ratios) from C3 to C7. Morphometric dimensions from the sagittal retrodiscal and retrovertebral regions as well as axial MRI dimensions were compared. Sagittal and axial spinal cord occupation ratios were defined and correlated with spinal canal dimensions. RESULTS: Multivariate analyses indicated reduced sagittal and axial anteroposterior (AP) spinal canal dimensions and a large reduction in transverse spinal canal dimensions at all spinal levels. There was a small significant correlation between AP sagittal spinal canal dimensions and axial transverse spinal canal dimensions at C3-C5, but not at C5-C6. Small correlations were noted between AP sagittal spinal canal dimensions and AP axial spinal cord and axial cross-sectional area occupation ratios at C3-C6, but there was no correlation with axial mediolateral spinal cord occupation ratios. CONCLUSIONS: The stenosis effect can involve any dimension, including the transverse spinal canal dimension, independent of other dimensions. Owing to the varied observed morphoanatomies, a classification algorithm that defines CCS specific phenotypes was formulated. Objectivizing the stenosis morphoanatomy may allow for data-driven patient-focused decompression approaches in the future.

The spectral composition of a white light influences its attractiveness to Culex pipiens mosquitoes.

Insect attraction to artificial light can potentially facilitate disease transmission by increasing contact between humans and vectors. Previous research has identified specific wavelength bands, such as yellow and red, that are unattractive to biting flies. However, narrow-band, non-white lights are unsuitable for home lighting use as their very poor color rendering is often considered aesthetically undesirable. The creation of a white light that is unattractive to insects has so far remained elusive. White light can be created by combining a number of narrow-band light-emitting diodes (LEDs). Through choice chamber experiments on Culex pipiens (Cx. pipiens) mosquitoes, we examine whether combining specific wavelength bands has an additive, subtractive or synergistic effect on insect attraction. We show that a white light created by combining narrow-band red, green and blue (RGB) LEDs is less attractive to Cx. pipiens than a broad-spectrum white light; and that a white light created by combining narrow-band blue and yellow LEDs is more attractive than a broad-spectrum white light. White light produced by RGB combinations could therefore serve as a safer and cheaper light in countries where phototactic vectors and vector-borne disease are endemic.

The New England Neurosurgical Society: growth and evolution over 70 years.

The New England Neurosurgical Society (NENS) was founded in 1951 under the leadership of its first President (Dr. William Beecher Scoville) and Secretary-Treasurer (Dr. Henry Thomas Ballantine). The purpose of creating the NENS was to unite local neurosurgeons in the New England area; it was one of the first regional neurosurgical societies in America. Although regional neurosurgical societies are important supplements to national organizations, they have often been overshadowed in the available literature. Now in its 70th year, the NENS continues to serve as a platform to represent the needs of New England neurosurgeons, foster connections and networks with colleagues, and provide research and educational opportunities for trainees. Additionally, regional societies enable discussion of issues uniquely relevant to the region, improve referral patterns, and allow for easier attendance with geographic proximity. In this paper, the authors describe the history of the NENS and provide a roadmap for its future. The first section portrays the founders who led the first meetings and establishment of the NENS. The second section describes the early years of the NENS and profiles key leaders. The third section discusses subsequent neurosurgeons who steered the NENS and partnerships with other societies. In the fourth section, the modern era of the NENS and its current activities are highlighted.

Postlaminectomy lumbopelvic sagittal changes in patients with developmental lumbar spinal stenosis grouped into Roussouly lumbopelvic sagittal profiles: 2- to 10-year prospective follow-up.

OBJECTIVE: Roussouly lumbopelvic sagittal profiles are associated with distinct pathologies or distinct natural histories and prognoses. The associations between developmental lumbar spinal stenosis (DLSS) and native lumbopelvic sagittal profiles are unknown. Moreover, the relative effects of multilevel decompression on lumbar sagittal alignment, geometrical parameters of the pelvis, and compensatory mechanisms for each of the Roussouly subtypes are unknown. This study aimed to explore the association between DLSS and native lumbar lordosis (LL) subtypes. It also attempts to understand the natural history of postlaminectomy lumbopelvic sagittal changes and compensatory mechanisms for each of the Roussouly subtypes and to define the critical lumbar segment or specific lordosis arc that is recruited after relief of the stenosis effect. METHODS: A total of 418 patients with multilevel DLSS were grouped into various Roussouly subtypes, and lumbopelvic sagittal parameters were prospectively compared at follow-up intervals of preoperative to < 2 years, 2 to < 5 years, and 5 to ≥ 10 years after laminectomy. The variables analyzed included LL, upper lordosis arc from L1 to L4, lower lordosis arc from L4 to S1, and segmental lordosis from L1 to S1. Pelvic parameters included pelvic incidence, sacral slope, pelvic tilt, and pelvic incidence minus LL values. RESULTS: Of the 329 patients who were followed up throughout this study, 33.7% had Roussouly type 1 native lordosis, whereas the incidence rates of types 2, 3, and 4 were 33.4%, 21.9%, and 10.9%, respectively. LL was not reduced in any of the Roussouly subtypes after multilevel decompressions. Instead, LL increased by 4.5° (SD 11.9°-from 27.3° [SD 11.5°] to 31.8° [SD 9.8°]) in Roussouly type 1 and by 3.1° (SD 11.6°-from 41.3° [SD 9.5°] to 44.4° [SD = 9.7°]) in Roussouly type 2. The other Roussouly types showed no significant changes. Pelvic tilt decreased significantly-by 2.8°, whereas sacral slope increased significantly-by 2.9° in Roussouly type 1 and by 1.7° in Roussouly type 2. The critical lumbar segment that recruits LL differs between Roussouly subtypes. Increments and changes were sustained until the final follow-up. CONCLUSIONS: The study findings are important in predicting patient prognosis, LL evolution, and the need for prophylactic or corrective deformity surgery. Multilevel involvement in DLSS and the high prevalence of Roussouly types 1 and 2 suggest that spinal canal dimensions are closely linked to the developmental evolution of LL.

Socioeconomic Implications of Professional Relationships within Modern Care Delivery Systems.

No physician can successfully deliver high-value patient care in the modern-day health care system in isolation. Delivery of effective patient care requires integrated and collaborative systems that depend on dynamic professional relationships among members of the health care team. An overview of the socioeconomic implications of professional relationships within modern care delivery systems and potential employment models is presented.

Artificial light and biting flies: the parallel development of attractive light traps and unattractive domestic lights.

Light trapping is an important tool for monitoring insect populations. This is especially true for biting Diptera, where light traps play a crucial role in disease surveillance by tracking the presence and abundance of vector species. Physiological and behavioural data have been instrumental in identifying factors that influence dipteran phototaxis and have spurred the development of more effective light traps. However, the development of less attractive domestic lights has received comparatively little interest but could be important for reducing interactions between humans and vector insects, with consequences for reducing disease transmission. Here, we discuss how dipteran eyes respond to light and the factors influencing positive phototaxis, and conclude by identifying key areas for further research. In addition, we include a synthesis of attractive and unattractive wavelengths for a number of vector species. A more comprehensive understanding of how Diptera perceive and respond to light would allow for more efficient vector sampling as well as potentially limiting the risk posed by domestic lighting.

Metabolic monitoring of second-generation antipsychotics: Evaluation of a pharmacist- and nurse-driven protocol.

OBJECTIVE: Second-generation antipsychotic therapy can lead to metabolic abnormalities, increasing the risk of cardiovascular disease and death in patients with serious mental illness. However, the literature suggests there is a lack of appropriate monitoring in individuals receiving these therapies. This study aims to evaluate whether the implementation of a pharmacist- and nurse-driven metabolic monitoring protocol will increase monitoring in patients prescribed second-generation antipsychotic therapy in an outpatient community mental health clinic. METHODS: A retrospective review of adult outpatients in a community mental health clinic who were prescribed second-generation antipsychotics was conducted from October 1, 2017, to March 31, 2019. Pre- and postprotocol implementation groups were compared to assess the impact of the protocol on the primary outcome of appropriateness in monitoring for metabolic parameters. RESULTS: A total of 160 patients who met the inclusion criteria were randomly selected and reviewed, allowing for 80 individuals in each group. Improvement in the appropriateness of monitoring was found for 4 of 5 metabolic parameters after protocol implementation, including blood pressure (17.5% to 43.8%, P < 0.001), weight (17.5% to 43.8%, P < 0.001), hemoglobin A1C (27.5% to 42.5%, P = 0.044), and lipid levels (17.5% to 31.3%, P = 0.04). Primary care physicians ordered most of the laboratory values (44.5% to 46.2%); however, pharmacists and nurses ordered 7% of laboratory tests after the protocol implementation. CONCLUSION: Despite the knowledge that second-generation antipsychotic therapies commonly lead to metabolic syndrome and therefore increased cardiovascular disease risk, monitoring for metabolic effects remains poor, and there is a lack in diversity of strategies to improve this monitoring. Although further research on the effectiveness of a pharmacist- and nurse-driven metabolic monitoring protocol in this setting is warranted, this protocol serves as an example of a novel strategy with the potential to improve metabolic monitoring of second-generation antipsychotic therapy.

Muscles innervated by a single motor neuron exhibit divergent synaptic properties on multiple time scales.

Adaptive changes in the output of neural circuits underlying rhythmic behaviors are relayed to muscles via motor neuron activity. Presynaptic and postsynaptic properties of neuromuscular junctions can impact the transformation from motor neuron activity to muscle response. Further, synaptic plasticity occurring on the time scale of inter-spike intervals can differ between multiple muscles innervated by the same motor neuron. In rhythmic behaviors, motor neuron bursts can elicit additional synaptic plasticity. However, it is unknown whether plasticity regulated by the longer time scale of inter-burst intervals also differs between synapses from the same neuron, and whether any such distinctions occur across a physiological activity range. To address these issues, we measured electrical responses in muscles innervated by a chewing circuit neuron, the lateral gastric (LG) motor neuron, in a well-characterized small motor system, the stomatogastric nervous system (STNS) of the Jonah crab, Cancer borealisIn vitro and in vivo, sensory, hormonal and modulatory inputs elicit LG bursting consisting of inter-spike intervals of 50-250 ms and inter-burst intervals of 2-24 s. Muscles expressed similar facilitation measured with paired stimuli except at the shortest inter-spike interval. However, distinct decay time constants resulted in differences in temporal summation. In response to bursting activity, augmentation occurred to different extents and saturated at different inter-burst intervals. Further, augmentation interacted with facilitation, resulting in distinct intra-burst facilitation between muscles. Thus, responses of multiple target muscles diverge across a physiological activity range as a result of distinct synaptic properties sensitive to multiple time scales.

Experimentally comparing the attractiveness of domestic lights to insects: Do LEDs attract fewer insects than conventional light types?

LED lighting is predicted to constitute 70% of the outdoor and residential lighting markets by 2020. While the use of LEDs promotes energy and cost savings relative to traditional lighting technologies, little is known about the effects these broad-spectrum "white" lights will have on wildlife, human health, animal welfare, and disease transmission. We conducted field experiments to compare the relative attractiveness of four commercially available "domestic" lights, one traditional (tungsten filament) and three modern (compact fluorescent, "cool-white" LED and "warm-white" LED), to aerial insects, particularly Diptera. We found that LEDs attracted significantly fewer insects than other light sources, but found no significant difference in attraction between the "cool-" and "warm-white" LEDs. Fewer flies were attracted to LEDs than alternate light sources, including fewer Culicoides midges (Diptera: Ceratopogonidae). Use of LEDs has the potential to mitigate disturbances to wildlife and occurrences of insect-borne diseases relative to competing lighting technologies. However, we discuss the risks associated with broad-spectrum lighting and net increases in lighting resulting from reduced costs of LED technology.

Light-emitting diode street lights reduce last-ditch evasive manoeuvres by moths to bat echolocation calls.

The light-emitting diode (LED) street light market is expanding globally, and it is important to understand how LED lights affect wildlife populations. We compared evasive flight responses of moths to bat echolocation calls experimentally under LED-lit and -unlit conditions. Significantly, fewer moths performed 'powerdive' flight manoeuvres in response to bat calls (feeding buzz sequences from Nyctalus spp.) under an LED street light than in the dark. LED street lights reduce the anti-predator behaviour of moths, shifting the balance in favour of their predators, aerial hawking bats.

The impacts of new street light technologies: experimentally testing the effects on bats of changing from low-pressure sodium to white metal halide.

Artificial light at night is a major feature of anthropogenic global change and is increasingly recognized as affecting biodiversity, often negatively. On a global scale, newer technology white lights are replacing orange sodium lights to reduce energy waste. In 2009, Cornwall County Council (UK) commenced replacement of existing low-pressure sodium (LPS) high intensity discharge (HID) street lights with new Phillips CosmoPolis white ceramic metal halide street lights to reduce energy wastage. This changeover provided a unique collaborative opportunity to implement a before-after-control-impact field experiment to investigate the ecological effects of newly installed broad spectrum light technologies. Activity of the bat species Pipistrellus pipistrellus, P. pygmaeus and Nyctalus/Eptesicus spp. was significantly higher at metal halide than LPS lights, as found in other studies of bat activity at old technology (i.e. mercury vapour) white light types. No significant difference was found in feeding attempts per bat pass between light types, though more passes overall were recorded at metal halide lights. Species-specific attraction of bats to the metal halide lights could have cascading effects at lower trophic levels. We highlight the need for further research on possible ecosystem-level effects of light technologies before they are installed on a wide scale.

A dietary conjugated linoleic acid treatment that slows renal disease progression alters renal cyclooxygenase-2-derived prostanoids in the Han: SPRD-cy rat.

A mixture of dietary conjugated linoleic acid (CLA) isomers reduces inflammation and mitigates disease progression in the Han:SPRD-cy rat model of chronic kidney disease. Since cyclooxygenase (COX) activities and prostanoid levels are higher in diseased kidneys in this rat, and dietary CLA can inhibit COX2 and prostanoid production in other tissues, the effects of dietary CLA were investigated. Kidney homogenates from normal and diseased Han:SPRD-cy rats were analyzed for prostanoid levels under various conditions: endogenous levels, steady-state levels (60-min incubations) and produced by COX isoforms. Thromboxane B(2) (TXB(2); TXA(2) metabolite), 6-keto-prostaglandin F(1α) (6-keto-PGF(1α); PGI(2) metabolite) and PGE(2) levels under these conditions were two- to ninefold higher in diseased kidneys. Dietary CLA resulted in ∼32%-53% lower levels of prostanoids produced by total COX and COX2 activities in normal and diseased kidneys and partially mitigated alterations in COX2 protein levels associated with disease. The COX1 protein and activity were higher in renal disease, resulting in increased production of TXB(2) and 6-ketoPGF(1α), but not PGE(2). Dietary CLA had no effect on COX1, however. Disease resulted in up to twofold higher ratios of TXB(2)/6-ketoPGF(1α), TXB(2)/PGE(2) and 6-ketoPGF(1α) /PGE(2), and dietary CLA partially mitigated these increases under several conditions. Elevated levels of renal membrane associated cytosolic phospholipase A(2) in diseased kidneys also were reduced by 50% with CLA feeding. The effects of CLA feeding on COX2 protein levels and activity indicate that the beneficial effect of dietary CLA in this renal disorder is mediated in part via effects on COX2-derived prostanoids.

High dose trans-10,cis-12 CLA increases lean body mass in hamsters, but elevates levels of plasma lipids and liver enzyme biomarkers.

The current study examined the efficacy of graded doses of c9,t11 and t10,c12 CLA isomers on body composition, energy expenditure, hepatic and serum lipid liver biomarkers in hamsters. Animals (n = 105) were randomized to seven treatments (control, 1, 2, 3% of c9,t11; 1, 2, 3% of t10,c12) for 28 days. After 28 days treatment, 1-3% of t10,c12 lowered (p < 0.05) body fat mass compared to the control group. The 1-3% t10,c12 and 3% c9,t11 fed groups showed higher (p < 0.05) lean mass compared to other groups. We observed unfavorable changes in plasma total cholesterol and non-HDL cholesterol levels in animals fed with 3% t10,c12 CLA isomers. The 2%, 3% t10,c12 groups presented elevated (p < 0.05) ALT levels. The present data suggest that a diet enriched with more than 2% t10, c12 led to liver malfunction and poses unfavorable changes on plasma lipid profiles. The 1% t10,c12 CLA lowered (p < 0.05) body fat mass and increased (p < 0.05) lean body mass. The c9,t11 CLA has less potent actions than t10,c12 CLA. We conclude that the actions of CLA on energy and lipid metabolism are form and dose dependent in the hamster model.

A diet with 35% of energy from protein leads to kidney damage in female Sprague-Dawley rats.

High-protein (HP) diets for weight loss remain popular despite questions surrounding overall safety. In a recent study using the pig model, we showed that long-term intakes from whole proteins at 35 % energy (en %) cause moderate renal histological damage. To examine whether this observation may be species specific or more generalisable, the effect of this diet in rats was examined. Using plant and animal whole proteins, 70-d-old female Sprague-Dawley rats were randomised to either a normal-protein (NP; 15 en %) or a HP (35 en %) diet for 4, 8, 12 and 17 months. Renal function was assessed by creatinine clearance and urinary protein levels, and pathology was assessed by examination of glomerular hypertrophy, glomerulosclerosis and tubulointerstitial fibrosis. Rats consuming the HP diet had 17 % higher kidney weights (P < 0·0001), three times higher proteinuria (P < 0·0001) and 27 % higher creatinine clearance (P = 0·0012) compared with those consuming the NP diet. Consistent with this, HP-fed rats had larger glomeruli (P < 0·0001) and more glomerulosclerosis (P = 0·0003) compared with NP-fed rats. The HP diet also resulted in altered levels of free monocyte chemoattractant protein-1 (P < 0·0001). The histological changes are consistent with those observed in the pig model. In contrast to the pig model, the elevated proteinuria and creatinine clearance observed in the rat model are also usually observed with HP consumption in human subjects. These results indicate that the rat is a useful model for HP effects on the kidney and, along with previous results using the pig model, suggest that long-term intake of high levels of protein may be detrimental to renal health.

Controlled evaluation of the effects of hyperbaric oxygen therapy on the behavior of 16 children with autism spectrum disorders.

Hyperbaric oxygen therapy (HBOT) has been used to treat individuals with autism. However, few studies of its effectiveness have been completed. The current study examined the effects of 40 HBOT sessions at 24% oxygen at 1.3 ATA on 11 topographies of directly observed behavior. Five replications of multiple baselines were completed across a total of 16 participants with autism spectrum disorders. No consistent effects were observed across any group or within any individual participant, demonstrating that HBOT was not an effective treatment for the participants in this study. This study represents the first relatively large-scale controlled study evaluating the effects of HBOT at the level of the individual participant, on a wide array of behaviors.

Trans-8, cis-10+ cis-9, trans-11-conjugated linoleic acid mixture alters body composition in Syrian golden hamsters fed a hypercholesterolaemic diet.

The effectiveness of conjugated linoleic acid (CLA) as a weight-loss nutraceutical continues to be debatable, suggesting that there may be value in exploring the physiological effects of the lesser-known isomers. The effects of the minor isomer, trans-8, cis-10 (t8, c10)-CLA, in the form of an equimolar mixture with the cis-9, trans-11 (c9, t11) isomer, on body weight and body composition, circulating glucose and lipid concentrations, and liver weights were studied in sixty male Syrian golden hamsters. Animals were randomised to receive for 28 d a semi-purified, hypercholesterolaemic diet (5% dietary fat and 0.25% cholesterol) supplemented at the 2% level with either the t8, c10+c9, t11-CLA mixture, c9, t11-CLA or trans-10, cis-12 (t10, c12)-CLA replacing lard and safflower-seed oil (control). Results show that compared with control, the t8, c10+c9, t11-CLA mixture and t10, c12-CLA-fed animals had lower (P < 0.0001) fat mass following supplementation. Animals consuming t10, c12-CLA also possessed higher lean mass compared with control and c9, t11-CLA groups (P < 0.001). However, the livers of these animals were larger (P < 0.0001) compared with those in the control and other CLA groups. Body weights of the hamsters did not differ across the experimental groups. CLA treatments had no effect on serum glucose or lipid profile, except for inducing higher (P < 0.05) non-HDL-cholesterol concentration with t10, c12-CLA compared with the c9, t11 isomer. Overall, these results indicate that in male hamsters fed a hypercholesterolaemic diet, the t8, c10+c9, t11-CLA mixture does not have an impact on blood lipid profile, but is able to effectively reduce fat mass, without incurring an accompanying liver enlargement.

Decreased Serum Hepatocyte Growth Factor (HGF) in Autistic Children with Severe Gastrointestinal Disease.

AIM: To assess serum Hepatocyte Growth Factor (HGF) levels in autistic children with severe gastrointestinal (GI) disease and to test the hypothesis that there is a relationship between GI pathology and HGF concentration. SUBJECTS AND METHODS: Serum from 29 autistic children with chronic digestive disease (symptoms for a minimum of 6-12 months), most with ileo-colonic lymphoid nodular hyperplasia (LNH-markedly enlarged lymphoid nodules) and inflammation of the colorectum, small bowel and/or stomach), and 31 controls (11 age matched autistic children with no GI disease, 11 age matched non autistic children without GI disease and 9 age matched non autistic children with GI disease) were tested for HGF using ELISAs. HGF concentration of autistic children with GI disease was compared to GI disease severity. RESULTS: Autistic children with GI disease had significantly lower serum levels of HGF compared to controls (autistic without GI disease; p = 0.0005, non autistic with no GI disease; p = 0.0001, and non autistic with GI disease; p = 0.001). Collectively, all autistic children had significantly lower HGF levels when compared to non autistic children (p < 0.0001). We did not find any relationship between severity of GI disease and HGF concentration in autistic children with GI disease. DISCUSSION: These results suggest an association between HGF serum levels and the presence of GI disease in autistic children and explain a potential functional connection between the Met gene and autism. The concentration of serum HGF may be a useful biomarker for autistic children, especially those with severe GI disease.

WITHDRAWN: Delayed acquisition of neonatal reflexes in newborn primates receiving a thimerosal-containing Hepatitis B vaccine: Influence of gestational age and birth weight.

This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

A high mixed protein diet reduces body fat without altering the mechanical properties of bone in female rats.

Long-term consumption of high-protein (HP) diets at 35% of energy is postulated to negatively influence bone health. Previous studies have not comprehensively examined the biochemical, physical, and biomechanical properties of bone required to arrive at this conclusion. Our objective in this study was to examine the long-term effect of a HP diet on bone metabolism, mass, and strength in rats. Adult female Sprague-Dawley rats (n = 80) were randomized to receive for 4, 8, 12, or 17 mo a normal-protein (NP) control diet (15% of energy) or a HP diet (35% of energy). Diets were balanced for calcium because the protein sources were rich in calcium. At each time point, measurements included weight, body composition, and bone mass using dual-energy X-ray absorptiometry, mechanical strength at the mid-diaphysis of femur and tibia, microarchitecture of femurs using microcomputerized tomography and serum osteocalcin, carboxy-terminal crosslinks of type I collagen (CTX), insulin-like growth factor-1 (IGF-1), leptin, and adiponectin. Effects of diet, time, and their interaction were tested using factorial ANOVA. The HP diet resulted in lower body weight, total body, and abdominal fat and higher lean mass. Serum leptin and adiponectin were greater in HP-fed than in NP-fed rats, but IGF-1 did not differ between the groups. Whereas the HP diet resulted in higher relative bone mineral content (g/kg) in the femur, tibia, and vertebrae, serum osteocalcin and CTX and bone internal architecture and biomechanical strength were unaffected. In conclusion, HP diets at 35% of energy lower body fat content without hindering the mechanical and weight-bearing properties of bone.

Low Serum Alpha-Antitrypsin Associated with Anti-PR-3 ANCA in Autistic Children with GI Disease.

AIM: To assess the possible relationship between serum alpha-1 antitrypsin (AAT) levels and anti-neutrophil cytoplasmic antibodies (ANCA) in autistic children with severe GI disease and to test the hypothesis that there is an association between low serum AAT levels, the presence of ANCA and inflammatory GI disease seen in some autistic children. SUBJECTS AND METHODS: Serum from 40 autistic children with chronic digestive disease (many with ileo-colonic lymphoid nodular hyperplasia (LNH) and inflammation of the colorectum, small bowel and/or stomach), and 41 controls (21 age matched autistic children with no GI disease and 20 age matched children without autism or GI disease) were tested using ELISAs designed to quantitate ANCA (anti-PR3), AAT and PR3 levels. RESULTS: We found that a significant number of autistic children with chronic digestive disease had anti-PR3 ANCA, high serum PR3 and high severity of disease when compared to controls. This same group of autistic children had low serum levels of AAT compared to controls, which also correlated with the presence of anti-PR3 ANCA, high serum PR3, as well as the severity of intestinal disease, particularly LNH and severe erythema. DISCUSSION: These results suggest a relationship between low AAT levels, ANCA and severity of GI disease seen in a subpopulation of ASD individuals. We suggest that low AAT levels may result in high levels of PR3, which may, in turn be associated with the presence of ANCA.