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Objective: Eosinophilic esophagitis (EoE) is a Th2 disease that presently is diagnosed and followed by clinical symptoms in the presence of endoscopic biopsies documenting elevated esophageal eosinophilia. To simplify clinical care, multiple studies have attempted to identify a disease specific serologic marker. None have been successful. The goal of this study was to employ custom designed Luminex multiplex bead assays to identify a reliable serologic marker for EoE., Methods: Luminex assays were employed to measure serum levels of 11 analytes associated with EoE (IL-5, lL13, periostin, eotaxin-3, thymic stromal lymphopoietin, and immunoglobulins) in a cohort of pediatric patients consisting of active EoE (n=30), EoE in remission (n=13), and controls (n=34)., Results: No analyte was found to be elevated or depressed in active EoE compared to the other groups. Additionally, among the cohort with active EoE, none of the 11 analytes correlated with peak esophageal eosinophilia, endoscopic features of EoE quantitatively defined by an EoE validated endoscopic reference score (EREFS), or esophageal thickness as determined by endosonography., Conclusion: This is the largest prospective survey of heterogeneous markers studied in a consecutive cohort to determine whether they could diagnose or follow EoE. Although none were identified in this cohort, Luminex provides a rapid, economical tool to simultaneously screen multiple sera for proteins that are increased or decreased in disease states., (© 2022 by the Association of Clinical Scientists, Inc.)

Background: Mental imagery (MI) may play a key role in the development of various mental disorders in adolescents. Adolescence is known to be a fragile life period, in which acceptance by one's favored peer group is extremely important, and social rejection is particularly painful. This is the first pilot study investigating MI and its relationship to social pain (SP)., Method: A sample of 80 adolescents (14-20 years; 75.3% female) completed a web-based quasi-experimental design about the contents and characteristics of their spontaneous positive and negative MI and associated emotions, and were asked to complete the Social Pain Questionnaire, the Becks Depression Inventory and the Social Phobia Inventory., Results: A higher score of SP was significantly associated with increased fear, sadness, and feelings of guilt, and less control over negative MI. Characteristics of negative MI were more precisely predicted by SP scores than depression- and social anxiety scores. Adolescents with higher SP-scores more often reported negative images including social situations and were more likely to perceive negative images in a combination of field-and observer perspectives than adolescents with lower SP scores., Conclusion: SP-sensitivity seems to be linked to unique characteristics of negative MI, which reveals the strong emotional impact of social exclusion in youths. The results do not allow causal conclusions to be drawn, but raise questions about previous studies comparing each imagery perspective individually.

Objectives: The eosinophilic esophagitis (EoE) endoscopic reference score (EREFS) was developed to analyze adults with EoE and has been successfully applied to a pediatric cohort. The present study compares EREFS in younger and older children with EoE., Methods: The 99 patients were divided among 3 cohorts: 44 active EoE (EoE-A); 16 EoE remission (EoE-R); and 39 controls (esophageal dysfunction but <15 eos/hpf). The cohorts were then subdivided into 2 groups: younger (≤10 years) and older (>10 years) that were compared based on the composite and the individual components of their EREFS., Results: EREFS identified EoE-A in all children with an area under the receiving operating characteristics curve (AUC) of 0.85, in older children with an AUC of 0.90 and in younger children with an AUC of 0.77. Mean EREFS for ≤10 years was 1.26 ± 1.19 and 2.71 ± 1.33 for >10 years (P < 0.01). The 3 most common findings in our entire EoE-A cohort and in both ages were furrows, edema, and exudates. EREFS in patients with EoE-A had similar specificities (0.88 vs 0.89) and positive predictive values (0.89 vs 0.91) in both ages., Conclusions: The present investigation confirms the utilization of EREFS in Pediatric EoE. Furthermore, EREFS can detect EoE and document response to treatment in both younger and older children. EREFS, however, predicted EoE in the older children with a higher sensitivity (0.89 vs 0.63) and a higher negative predictive value (0.87 vs 0.59) than was seen in the younger cohort.

Pyoderma gangrenosum (PG) is a rare, necrotizing dermatologic condition associated with neoplastic and immune dysregulatory states, including adult and pediatric inflammatory bowel disease (IBD). Over the last decade, the elucidation of inflammatory mediators in PG has led to a plethora of localized and systemic corticosteroid sparing therapies including antibiotics, antiinflammatory, and immunomodulatory agents. Herein, we describe the case of a 17-year-old female with ulcerative colitis in clinical remission, who presented with a long-standing, large, deep, and painful lower extremity PG lesion. Following failed attempts both at local and at systemic therapies, her PG was successfully treated with the tumor necrosis factor-alpha (TNF-α) monoclonal antibody adalimumab, and the lesion remains in remission after four years of subcutaneous anti-TNF therapy. This case serves as the basis for our presenting a review of the pathogenesis, diagnostic criteria, differential diagnosis, therapies and treatment outcomes for pediatric IBD-associated PG. Our experience adds to earlier reports suggesting anti-TNF-α biologic therapy is most likely to achieve long-term resolution of IBD-associated PG in children and adolescents with severe lesions or who failed other treatments., Competing Interests: Disclosure: The authors declare no funding or conflicts of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background and Objective: EUS has been shown in two small series to be capable of documenting increases in the total esophageal wall thickness (TWT) in children and adults with eosinophilic esophagitis (EoE). To apply EUS-derived TWT in clinical situations or in scientific investigations in pediatric EoE, measurements of esophageal TWT in children of differing ages and heights are required., Materials and Methods: Thirty patients (18M: 12F, 7 months to 20 years and 10 months) with a history of esophageal symptoms, but no endoscopic or histologic criteria of EoE were studied using a through the scope 20 MHZ Olympus Ultrasound miniprobe UM-3R (Olympus America, Center Valley Pa 18034) through a GIF Q180 or 160 (Olympus) standard pediatric upper endoscope. The mucosa, the mucosa plus submucosa, and the TWT were measured in the mid- and distal esophagus immediately before taking diagnostic biopsies., Results: Measurements from both sites showed a statistically significant increase in TWT as a function of age (P < 0.001) and height (P < 0.001), as did the individual layers. The width of the mucosa and the submucosa were equivalent and together, they contributed more than half of the entire TWT. There were no significant differences between the means of the mid- and distal esophageal measurements. A multiple regression equation that can predict TWT based on age, with 95% confidence limits, is presented., Conclusions: EUS has demonstrated that esophageal TWT in a cohort of control children correlates with height and with age and has provided insights into the organization of the esophageal wall. Esophageal TWT values obtained by EUS can now be interpreted to recognize esophageal wall thickening throughout childhood., Competing Interests: None

Large urban trees have many benefits. However, falling branches pose a serious hazard to both people and infrastructure. In several tree species, aerial roots grow down from branches to the ground. These roots are capable of thickening to support the branches, lessening the risk of tree failure. Unfortunately, in urban environments most aerial roots die before reaching the ground. Here, we report a new method for encouraging aerial roots to reach the ground, developed by the second-year botany class at UNSW Sydney. Our class tested three experimental treatments on aerial roots of Ficus rubiginosa Desf. ex Vent. (Port Jackson Fig)-PVC pipes filled with sphagnum moss, PVC pipes filled with potting mix, and PVC pipes filled with sphagnum moss and topped with funnels to catch extra rainwater. All three treatments significantly improved aerial root growth, with 26 of the 30 (87%) treatment roots reaching the ground after one year compared to 0 of the 10 control roots. Our method was successful for roots up to 3 m above the ground, suggesting the potential growth rate of aerial roots is substantial when conditions are favourable. Our novel approach is an attractive and cost-effective alternative to slings and other artificial supports. This project is an example of using undergraduate practical classes to teach science while simultaneously addressing important real-world problems., Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: Altered vascular flow is known to both play a role in the pathogenesis and influence the severity of inflammatory bowel disease (IBD). This phenomenon has been described in other systemic conditions and contributes to disease progression by facilitating inflammation and thrombosis. Microvascular dysfunction may represent an early sign of generalized vascular disease (VD). It manifests by failure to achieve a normal response of vasodilation and increased blood flow following a period of vaso-occlusion. Although thromboembolic complications are well described in IBD, their pathogenesis is not fully understood. This study sought to assess microvascular responsiveness in pediatric subjects with IBD, by recording postocclusion peripheral arterial pulsatile volume changes., Patients and Methods: A total of 32 pediatric subjects were studied, including 16 with IBD and 16 age-matched controls. All patients with IBD were in clinical remission, and none had known VD. Vascular reactivity was evaluated using the Itamar Medical EndoPAT2000, a noninvasive device utilizing plethysmography to measure microvascular flow. Results were reported as the reactive hyperemia index (RHI), indicating post- to preocclusion pulsatile volume changes., Results: Baseline characteristics, including body mass index, plasma lipid levels, hemoglobin, and serum albumin, were similar in both study groups. All patients with IBD were in clinical remission, assessed by standard disease activity scoring methods. Measurements of microvascular function indicated patients with IBD exhibited a mean RHI both within the range associated with VD risk in adults (≤1.67) and significantly lower than that in controls (IBD vs control = 1.66 vs 2.02, P = 0.036)., Conclusions: Microvascular plethysmography is a safe and noninvasive method for assessing microvascular function in children with IBD. Patients with IBD in clinical remission demonstrate an attenuated, postocclusion microvascular hyperemic response, compared with the normal response in controls. These findings suggest pediatric IBD subjects with a mean RHI within the VD "at risk" range should be monitored for thromboembolic phenomena. Further studies in a larger patient population and over longer periods should be conducted to validate our findings and to determine the importance of these measurements in guiding IBD management.

Purpose: In the evolution of the minimally invasive treatment of vertebral compression fractures, vertebral body stenting (VBS) was developed to reduce intraoperative and secondary loss of vertebral height. Particularly in combination with the usage of biodegradable cement, the influence of VBS on the rate of intraoperative complications and long-term outcome is unclear. The purpose of this study was to investigate the differences between balloon kyphoplasty (BKP) and VBS regarding their long-term clinical and radiological outcome in combination with calcium phosphate (CaP) application instead of polymethyl methacrylate (PMMA)., Methods: This retrospective study included 49 patients with fresh mono-segmental thoracolumbar fractures without neurological signs treated with VBS or BKP and CaP cement (Calcibone). The outcome was evaluated with the visual analogue pain scale (VAS), the Oswestry disability score (ODI), and radiologically assessed., Results: In the course of the radiological follow-up, the VBS group showed statistically significant less vertebral height loss than the BKP group. However, with respect to VAS and ODI scores there were no statistically significant differences between the VBS and BKP group in the clinical follow-up. The rate of cement leakage was comparable in both groups., Conclusions: Both techniques facilitated good clinical results in combination with absorbable cement augmentation. In particular, the VBS enabled us to benefit from the advantages of the resorbable isothermic CaP cement with an improved radiological outcome in the long term compared to BKP. However, there was a mentionable loss of reduction in the follow-up in both groups compared to previously published data with PMMA cement. These slides can be retrieved under Electronic Supplementary Material.

Objectives: Helicobacter pylori (Hp) are the most common agents causing gastric mucosal injury worldwide. Foveolar hyperplasia is a key component of the stomach's reaction to injury. This study examines histopathologic characteristics associated with Helicobacter pylori and with non- Helicobacter pylori-associated gastropathy in children and adolescents, and compares the prevalence of foveolar hyperplasia among these disease subgroups and normal control subjects., Methods: Eighty-one gastric antral and corpus biopsies from subjects 2-19 years of age were studied. Twenty-two subjects with Helicobacter pylori gastritis were compared to 23 with non-Helicobacter pylori gastropathy and to 36 controls (normal biopsies). Foveolar length, full mucosal thickness, and the foveolar length: full mucosal thickness ratio were derived by a morphometric technique previously developed to analyze adult gastric tissue., Results: Compared to controls, Helicobacter pylori gastritis demonstrated significant increases in antral foveolar length (P < .0001), full mucosal thickness (P < .0001), as well as corpus foveolar length (P < .05) and corpus full mucosal thickness (P < .05). Non-Helicobacter pylori-associated gastropathy also was characterized by increased antral foveolar length (P < .0001) and full mucosal thickness (P < .001) but corresponding corpus measurements did not differ from controls. Antral foveolar length in non-Helicobacter pylori gastropathy was increased, when compared to Helicobacter pylori gastritis (P < .05), while corpus values were not. The non-Helicobacter pylori gastropathy group demonstrated increased antral foveolar length: full mucosal thickness ratios, compared with Helicobacter pylori gastritis (P < .001) and with normal controls (P < .0001)., Discussion: An objective, quantitative approach to measuring foveolar hyperplasia in adults was successfully applied to pediatric biopsies and yielded a richer characterization of gastric pathology in children. Foveolar hyperplasia appears to be a generalized phenomenon in the presence of pediatric Helicobacter pylori gastritis but is limited to the antrum in non-Helicobacter pylori gastropathy., (© 2018 John Wiley & Sons Ltd.)

Proteolytic cleavage of the amyloid precursor protein (APP) by α-, β- and γ-secretases is a determining factor in Alzheimer's disease (AD). Imbalances in the activity of all three enzymes can result in alterations towards pathogenic Aβ production. Proteolysis of APP is strongly linked to its subcellular localization as the secretases involved are distributed in different cellular compartments. APP has been shown to dimerize in cis-orientation, affecting Aβ production. This might be explained by different substrate properties defined by the APP oligomerization state or alternatively by altered APP monomer/dimer localization. We investigated the latter hypothesis using two different APP dimerization systems in HeLa cells. Dimerization caused a decreased localization of APP to the Golgi and at the plasma membrane, whereas the levels in the ER and in endosomes were increased. Furthermore, we observed via live cell imaging and biochemical analyses that APP dimerization affects its interaction with LRP1 and SorLA, suggesting that APP dimerization modulates its interplay with sorting molecules and in turn its localization and processing. Thus, pharmacological approaches targeting APP oligomerization properties might open novel strategies for treatment of AD.

Early after entry into monocytes, macrophages, dendritic cells, and resting CD4 T cells, HIV encounters a block, limiting reverse transcription (RT) of the incoming viral RNA genome. In this context, dNTP triphosphohydrolase SAM domain and HD domain-containing protein 1 (SAMHD1) has been identified as a restriction factor, lowering the concentration of dNTP substrates to limit RT. The accessory lentiviral protein X (Vpx) proteins from the major simian immunodeficiency virus of rhesus macaque, sooty mangabey, and HIV-2 (SIVsmm/SIVmac/HIV-2) lineage packaged into virions target SAMHD1 for proteasomal degradation, increase intracellular dNTP pools, and facilitate HIV cDNA synthesis. We find that virion-packaged Vpx proteins from a second SIV lineage, SIV of red-capped mangabeys or mandrills (SIVrcm/mnd-2), increased HIV infection in resting CD4 T cells, but not in macrophages, and, unexpectedly, acted in the absence of SAMHD1 degradation, dNTP pool elevation, or changes in SAMHD1 phosphorylation. Vpx rcm/mnd-2 virion incorporation resulted in a dramatic increase of HIV-1 RT intermediates and viral cDNA in infected resting CD4 T cells. These analyses also revealed a barrier limiting HIV-1 infection of resting CD4 T cells at the level of nuclear import. Single amino acid changes in the SAMHD1-degrading Vpx mac239 allowed it to enhance early postentry steps in a Vpx rcm/mnd-2-like fashion. Moreover, Vpx enhanced HIV-1 infection of SAMHD1-deficient resting CD4 T cells of a patient with Aicardi-Goutières syndrome. These results indicate that Vpx, in addition to SAMHD1, overcomes a previously unappreciated restriction for lentiviruses at the level of RT that acts independently of dNTP concentrations and is specific to resting CD4 T cells.

The nucleoside analog cytarabine (Ara-C) is an essential component of primary and salvage chemotherapy regimens for acute myeloid leukemia (AML). After cellular uptake, Ara-C is converted into its therapeutically active triphosphate metabolite, Ara-CTP, which exerts antileukemic effects, primarily by inhibiting DNA synthesis in proliferating cells. Currently, a substantial fraction of patients with AML fail to respond effectively to Ara-C therapy, and reliable biomarkers for predicting the therapeutic response to Ara-C are lacking. SAMHD1 is a deoxynucleoside triphosphate (dNTP) triphosphohydrolase that cleaves physiological dNTPs into deoxyribonucleosides and inorganic triphosphate. Although it has been postulated that SAMHD1 sensitizes cancer cells to nucleoside-analog derivatives through the depletion of competing dNTPs, we show here that SAMHD1 reduces Ara-C cytotoxicity in AML cells. Mechanistically, dGTP-activated SAMHD1 hydrolyzes Ara-CTP, which results in a drastic reduction of Ara-CTP in leukemic cells. Loss of SAMHD1 activity-through genetic depletion, mutational inactivation of its triphosphohydrolase activity or proteasomal degradation using specialized, virus-like particles-potentiates the cytotoxicity of Ara-C in AML cells. In mouse models of retroviral AML transplantation, as well as in retrospective analyses of adult patients with AML, the response to Ara-C-containing therapy was inversely correlated with SAMHD1 expression. These results identify SAMHD1 as a potential biomarker for the stratification of patients with AML who might best respond to Ara-C-based therapy and as a target for treating Ara-C-refractory AML.

Aim: To determine if packed red blood cell transfusions contribute to the development of parenteral nutrition associated liver disease., Methods: A retrospective chart review of 49 premature infants on parenteral nutrition for > 30 d who received packed red blood cell (PRBC) transfusions was performed. Parenteral nutrition associated liver disease was primarily defined by direct bilirubin (db) > 2.0 mg/dL. A high transfusion cohort was defined as receiving > 75 mL packed red blood cells (the median value). Kaplan-Meier plots estimated the median volume of packed red blood cells received in order to develop parenteral nutrition associated liver disease., Results: Parenteral nutritional associated liver disease (PNALD) was noted in 21 (43%) infants based on db. Among the 27 high transfusion infants, PNALD was present in 17 (64%) based on elevated direct bilirubin which was significantly greater than the low transfusion recipients. About 50% of the infants, who were transfused 101-125 mL packed red blood cells, developed PNALD based on elevation of direct bilirubin. All infants who were transfused more than 200 mL of packed red blood cells developed PNALD. Similar results were seen when using elevation of aspartate transaminase or alanine transaminase to define PNALD., Conclusion: In this retrospective, pilot study there was a statistically significant correlation between the volume of PRBC transfusions received by premature infants and the development of PNALD., Competing Interests: Conflict-of-interest statement: None of the authors involved in this study have any conflicts of interest.

Unlabelled: Type I interferons (IFNs), including IFN-α, upregulate an array of IFN-stimulated genes (ISGs) and potently suppress Human immunodeficiency virus type 1 (HIV-1) infectivity in CD4(+) T cells, monocyte-derived macrophages, and dendritic cells. Recently, we and others identified ISG myxovirus resistance 2 (MX2) as an inhibitor of HIV-1 nuclear entry. However, additional antiviral blocks exist upstream of nuclear import, but the ISGs that suppress infection, e.g., prior to (or during) reverse transcription, remain to be defined. We show here that the HIV-1 CA mutations N74D and A105T, both of which allow escape from inhibition by MX2 and the truncated version of cleavage and polyadenylation specific factor 6 (CPSF6), as well as the cyclophilin A (CypA)-binding loop mutation P90A, all increase sensitivity to IFN-α-mediated inhibition. Using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology, we demonstrate that the IFN-α hypersensitivity of these mutants in THP-1 cells is independent of MX2 or CPSF6. As expected, CypA depletion had no additional effect on the behavior of the P90A mutant but modestly increased the IFN-α sensitivity of wild-type virus. Interestingly, the infectivity of wild-type or P90A virus could be rescued from the MX2-independent IFN-α-induced blocks in THP-1 cells by treatment with cyclosporine (Cs) or its nonimmunosuppressive analogue SDZ-NIM811, indicating that Cs-sensitive host cell cyclophilins other than CypA contribute to the activity of IFN-α-induced blocks. We propose that cellular interactions with incoming HIV-1 capsids help shield the virus from recognition by antiviral effector mechanisms. Thus, the CA protein is a fulcrum for the dynamic interplay between cell-encoded functions that inhibit or promote HIV-1 infection., Importance: HIV-1 is the causative agent of AIDS. During acute HIV-1 infection, numerous proinflammatory cytokines are produced, including type I interferons (IFNs). IFNs can limit HIV-1 replication by inducing the expression of a set of antiviral genes that inhibit HIV-1 at multiple steps in its life cycle, including the postentry steps of reverse transcription and nuclear import. This is observed in cultured cell systems, as well as in clinical trials in HIV-1-infected patients. The identities of the cellular antiviral factors, their viral targets, and the underpinning mechanisms are largely unknown. We show here that the HIV-1 Capsid protein plays a central role in protecting the virus from IFN-induced inhibitors that block early postentry steps of infection. We further show that host cell cyclophilins play an important role in regulating these processes, thus highlighting the complex interplay between antiviral effector mechanisms and viral survival., (Copyright © 2016 Bulli et al.)

Aim: To determine whether hepatocyte lipogenesis, in an in vitro cell culture model, is modulated by adjusting culture media monosaccharide content and concentration., Methods: Hepatocytes (Huh7), demonstrating glucose and fructose uptake and lipid biosynthesis, were incubated in culture media containing either glucose alone (0.65-0.72 mmol/L) or isosmolar monosaccharide (0.72 mmol/L) comprising fructose:glucose (F:G) molar ratios ranging from 0.58-0.67. Following a 24-h incubation, cells were harvested and analyzed for total protein, triglyceride (TG) and cholesterol (C) content. Significant differences (P < 0.05) among groups were determined using analysis of variance followed by Dunnett's test for multiple comparisons., Results: After a 24 h incubation period, Huh7 cell mass and viability among all experimental groups were not different. Hepatocytes cultured with increasing concentrations of glucose alone did not demonstrate a significant change either in C or in TG content. However, when the culture media contained increasing F:G molar ratios, at a constant total monosaccharide concentration, synthesis both of C and of TG increased significantly [F:G ratio = 0.58, C/protein (μg/μg) = 0.13; F:G = 0.67, C/protein = 0.18, P < 0.01; F:G ratio = 0.58, TG/protein (μg/μg) = 0.06; F:G ratio = 0.67, TG/protein = 0.11, P < 0.01]., Conclusion: In an in vitro hepatocyte model, glucose or fructose plus glucose support total cell mass and lipogenic activity. Increasing the fructose:glucose molar ratio (but not glucose alone) enhances triglyceride and cholesterol synthesis. These investigations demonstrate fructose promotes hepatocellular lipogenesis, and they provide evidence supporting future, in vivo studies of fructose's role in the development of hepatic steatosis and non-alcoholic fatty liver disease.

Objective: Cellular uptake of folate is mediated by folate receptor (FR)α. Prior studies indicate that a FRα autoantibody (FRAb) is implicated in poor pregnancy outcomes. The aims of this study were to determine the prevalence of FRAbs in women with preterm and term pregnancies, and to investigate the role of maternal FRAbs in preterm birth., Methods: This prospective observational study included 23 mothers and 25 preterm infants (two twin births) born at gestational age (GA) ≤32 wk and/or birth weight ≤1500 g (group 1) and 25 mother-term infant pairs (infants born at GA ≥37 wk, group 2). Blocking and binding FRAbs in maternal and in cord blood were determined. The association between maternal FRAbs and pregnancy outcome was measured using multiple logistic regression, adjusted for maternal age and previous preterm birth., Results: The prevalence of FRAbs was 65.2% in women with preterm birth, which was twofold higher than in those with term pregnancy (28%; relative risk [RR], 2.3; 95% confidence interval [CI], 1.2-4.7). The prevalence of FRAbs in preterm infants (64%) was significantly higher than in term infants (24%; RR, 2.7; 95% CI, 1.3-5.7). Pregnant women with positive FRAbs had 4.9 times higher odds of having preterm birth (odds ratio, 4.9; 95% CI, 1.4-17.7), adjusted for maternal age and previous preterm birth., Conclusions: These findings suggest that the presence of FRAbs might be a contributing factor to preterm birth, which could be prevented with appropriate testing and therapeutic interventions. Further studies are warranted to investigate the possible mechanisms of fetal sensitization resulting in FRAb production in utero and its possible clinical correlates., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Recently, publications in adults and children have documented a potential role of Helicobacter pylori (H. pylori) in decreasing the likelihood of obesity. The present study compares the prevalence of H. pylori colonization between obese (body mass index [BMI] ≥ 95th percentile) and healthy weight (BMI ≥ 5th to <85th percentiles) children seen at an inner city medical center in the United States., Methods: This retrospective study reviewed clinical features, BMI, and gastric histology of consecutive children aged 1-18 years undergoing an esophagogastroduodenoscopy. BMI percentile was calculated for age and gender. Helicobacter pylori colonization was determined by histopathologic identification of the organism. Multiple logistic regression was employed to measure the association between BMI and H. pylori colonization, controlling for baseline age, gender, and presenting symptoms., Results: Among 340 patients (51.5% female, mean age of 10.5 ± 4.7 years), 98 (29%) were obese and 173 (51%) were healthy weight. The H. pylori colonization rate of the entire cohort was 18.5% (95% CI = 14.7-23.0%). Among obese children, 10% had H. pylori colonization compared to 21% of the healthy weight children (RR = 2.1, 95% CI = 1.1-4.0). Conversely, 39% of noncolonized children, but only 21% of the infected children, were obese (RR = 1.8, 95% CI = 1.1-3.3). Multivariate analysis revealed that being colonized with H. pylori is associated with a 50% reduction in the odds of being obese (adjusted OR = 0.5, 95% CI = 0.2-1.0)., Conclusions: Our findings in a North American cohort are in agreement with studies from Asia and Europe suggesting that H. pylori infection decreases the prevalence of obesity in children. Further work to characterize the extent and nature of this relationship is warranted., (© 2014 John Wiley & Sons Ltd.)

Hepatic involvement is often encountered in gastrointestinal (GI) diseases, in part because of the close anatomic and physiologic relations between the liver and GI tract. Drainage of the mesenteric blood supply to the portal vein permits absorbed and/or translocated nutrients, toxins, bacterial elements, cytokines, and immunocytes to gain hepatic access. Liver problems in digestive disorders may range from nonspecific hepatocellular enzyme elevations to significant pathologic processes that may progress to end-stage liver disease. Hepatobiliary manifestations of primary GI diseases in childhood and adolescence are not uncommon and include several well-described associations, such as sclerosing cholangitis with inflammatory bowel disease. Liver damage may also result from the effects of drugs used to treat GI diseases, for example, the hepatotoxicity of immunomodulatory therapies. This review highlights the important features of the hepatic and biliary abnormalities associated with 3 common pediatric GI conditions: inflammatory bowel disease, celiac disease, and cystic fibrosis.

Objectives: ω-3 Fatty acids (FAs), natural ligands for the peroxisome proliferator-activated receptor-α (PPAR-α), attenuate parenteral nutrition-associated liver disease (PNALD). However, the mechanisms underlying the protective role of ω-3 FAs are still unknown. The aim of this study was to determine the effects of ω-3 FAs on hepatic triglyceride (TG) accumulation in a murine model of PNALD and to investigate the role of PPAR-α and microsomal triglyceride transfer protein (MTP) in this experimental setting., Methods: 129S1/SvImJ wild-type or 129S4/SvJaePparatm/Gonz/J PPAR-α knockout mice were fed chow and water (controls); oral, fat-free PN solution only (PN-O); PN-O plus intraperitoneal (IP) ω-6 FA-predominant supplements (PN-ω-6); or PN-O plus IP ω-3 FA (PN-ω-3). Control and PN-O groups received sham IP injections of 0.9% NaCl. Hepatic histology, TG and cholesterol, MTP activity, and PPAR-α messenger RNA were assessed after 19 days., Results: In all experimental groups, PN feeding increased hepatic TG and MTP activity compared with controls. Both PN-O and PN-ω-6 groups accumulated significantly greater amounts of TG when compared with PN-ω-3 mice. Studies in PPAR-α null animals showed that PN feeding increases hepatic TG as in wild-type mice. PPAR-α null mice in the PN-O and PN-ω-6 groups demonstrated variable degrees of hepatic steatosis, whereas no evidence of hepatic fat accumulation was found after 19 days of oral PN plus IP ω-3 FAs., Conclusions: PN induces TG accumulation (steatosis) in wild-type and PPAR-α null mice. In PN-fed wild-type and PPAR-α null mice given IP ω-3 FAs, reduced hepatic TG accumulation and absent steatosis are found. Prevention of steatosis by ω-3 FAs results from PPAR-α-independent pathways., (© 2013 American Society for Parenteral and Enteral Nutrition.)

Objectives: Gangliosides are glycosphingolipids, rich in colostrum and in membrane microdomains, which promote enterocyte growth and differentiation, and modulate TH1/TH2 responses. In an in vitro intestinal explant model of necrotizing enterocolitis (NEC), gangliosides have been shown to ameliorate intestinal injury; however, possible immunomodulatory mechanisms associated with this observation, as well as potential in vivo protective effects of gangliosides, remain unknown. The present study evaluates the effects of dietary GD3, the predominant ganglioside in neonatal rat intestine, both on the clinicopathologic expression of disease and on ileal Foxp3+ T regulatory cell immune responses in an experimental NEC model., Methods: Newborn rat pups were fed gavage formula (NEC) or formula supplemented with 15 μg/mL GD3 (GD3-NEC). Dam-fed (DF) littermates served as controls. NEC was induced by asphyxia and cold stress. At 96 hours, ileal gross and histologic changes were evaluated, and ileal cytokine profiles, Foxp3 expression, and Foxp3+ cell numbers were determined., Results: GD3 decreased the incidence and gross and histopathologic severity of NEC. Ileal Foxp3 expression and Foxp3+ cell numbers were significantly decreased in the NEC group compared with DF. GD3 increased ileal Foxp3 expression and Foxp3+ cell numbers, in association with upregulation of anti-inflammatory cytokine interleukin (IL)-10 and chemokines, tissue inhibitor of metalloproteinases 1, IL-1 receptor antagonist (IL-1ra), and suppressed proinflammatory mediators., Conclusions: These data suggest that dietary GD3 protects newborn rats from NEC, in part, by augmenting mucosal Foxp3+ T regulatory immune responses.

Introduction: It is thought that patients with cardiomyopathy have an increased risk of cardiac arrest on induction of anesthesia, but there is little available data. The purpose of this study was to identify the incidence and potential risk factors for cardiac arrest upon induction of anesthesia in children with cardiomyopathy in our institution., Methods: A retrospective chart review was performed. Eligible patients included patients admitted between 1998 and 2008 with the International Statistical Classification of Disease code for cardiomyopathy (ICD-9 code 425) who underwent airway intervention for sedation or general anesthesia in the operating room, cardiac diagnostic and interventional unit (CDIU) or intensive care unit. Patients undergoing emergency airway intervention following cardiovascular collapse were excluded. For each patient, we recorded patient demographics, disease severity, anesthesia location, and anesthetic technique., Results: One hundred and twenty-nine patients with cardiomyopathy underwent a total of 236 anesthetic events, and four cardiac arrests were identified. One was related to bradycardia (HR<60), two were attributed to bradycardia in association with severe hypotension (systolic blood pressure<45), and the fourth arrest was related to isolated severe hypotension. Two occurred in the operating suite and two in the CDIU. There was no resulting mortality. One patient progressed to heart transplantation. Multiple combinations of anesthetic drugs were used for induction of anesthesia., Conclusion: We performed a review of the last 10 years of anesthesia events in children with cardiomyopathy. We report four cardiac arrests in two patients and 236 anesthetic events (1.7%). To the best of our knowledge, this is the largest review of these patients to date but is limited by its retrospective nature. The low cardiac arrest incidence prevents the identification of risk factors and the development of a cardiac arrest risk predictive clinical tool., (© 2011 Blackwell Publishing Ltd.)

The performance of endoscopy in children generally requires the concomitant administration of sedation to ensure the patient's safety, comfort, and cooperation throughout the procedures. New pharmacological agents, increased procedural volume, variable access to anesthesia support, and improvement in endoscopic technique have contributed to vast differences in sedation regimens for gastrointestinal procedures in patients of all ages. To better understand variation in practice patterns among pediatric gastroenterologists, the NASPGHAN Endoscopy and Procedures Committee surveyed 103 NASPGHAN members during a recent NASPGHAN national meeting. The results of this survey confirm that sedation practices vary widely and reflect continued uncertainty regarding optimal sedation regimens for pediatric endoscopy.

GER is a common reason for pediatric office visits and referrals to a pediatric gastroenterologist. This condition frequently is benign, and it is self-limited in most infants. Although a thorough history and complete physical examination usually are adequate to diagnose GER, a high index of suspicion must be maintained for other diagnoses associated with recurrent emesis, including metabolic disorders, as well as for other gastrointestinal conditions, such as pyloric stenosis and abnormalities of intestinal rotation. Behavioral or lifestyle modification usually can be implemented empirically to diagnose and manage a suspected case of uncomplicated GER. When this fails, medical therapy can be initiated, employing either a step-up or step-down approach with a PPI or H2RA. With the proven efficacy of PPIs and their availability to children, medical treatment has become the mainstay of therapy in severely affected patients; nevertheless, anti-reflux surgery is still widely performed in children with GER. Pediatricians and other primary care providers often manage infants and children who have gastrointestinal complaints, prior to referral to a pediatric gastroenterologist. Hence, they have the responsibility to educate children and families about GER, its natural history, complications, and therapeutic options. A careful history and physical examination, informed use of diagnostic studies, and a consistent approach to medical treatment are important principles that are required to guarantee the success of GER management in infants and children.

Objectives: Although many children with otolaryngologic (ENT) symptoms are being treated for gastroesophageal reflux (GER), how to diagnose GER in children with primarily or exclusively ENT symptoms has yet to be determined. This study compares the incidences of pathologic GER in the upper verses the lower esophagus in a cohort of children with ENT symptoms that were screened for GER., Methods: The results of extended dual channel intraesophageal pH probe monitoring obtained from 14 infants and 14 children with ENT symptoms were retrospectively analyzed. The percent of total monitoring time that the pH was less than 4, reflux index (RI) was determined. The upper limits of normal distal and proximal esophageal RI were based on published data. To evaluate our results, upper esophageal reflux (UER) was also determined in 27 infants and children without ENT or pulmonary symptoms, who had normal lower esophageal reflux (LER) values., Results: Mean upper esophageal RIs in the infants and children with normal LER were similar to previously published values for control infants and adults. Four (29%) of the ENT infants, 11 (79%) of the older ENT children, and 54% of the entire cohort had increased esophageal acid exposure. However, nine (60%) of the 15 pediatric ENT patients with GER had pH abnormalities limited to the upper esophagus., Conclusions: Standard distal pH probe monitoring alone gives a false negative result in a substantial proportion of the infants and children with ENT symptoms being evaluated for GER. Beyond its value in clinical practice, UER testing should be employed in research studies that evaluate the impact of GER therapy on ENT symptoms.

Objectives: To determine the results of diagnostic evaluation and the effects of nutritional intervention on energy consumption, weight gain, growth, and clinical status of children with neurodevelopmental disabilities and suspected feeding disorders., Methods: We studied 79 children with moderate to severe motor or cognitive dysfunction (male:female, 38:41; age, 5.8 +/- 3.7 years) who were referred for diagnosis and treatment of feeding or nutritional problems. Initial assessments included a 3-day calorie intake record, videofluoroscopic swallowing study (VFSS), 24-hour intraesophageal pH monitoring, milk scintigraphy, and esophagogastroduodenoscopy., Results: These studies demonstrated gastroesophageal reflux (GER) with or without aspiration in 44 of 79 patients (56%), oropharyngeal dysphagia in 21 (27%), and aversive feeding behaviors in 14 (18%). Diagnosis-specific approaches included medical GER therapy in 20 patients (25%), fundoplication plus gastrostomy tube (GT) in 18 (23%), oral supplements in 17 (22%), feeding therapy only in 14 (18%), and GT only in 10 (13%). After 24.6 +/- 3.0 months, relative calorie intake, expressed as intake (kcal/d)/recommended daily allowance (RDA, kcal/d), improved significantly (initial:final = 0.78 +/- 0.36:1.23 +/- 0.27). The z scores increased significantly for both weight (initial:final = -2.80 +/- 1.33:-0.81 +/- 0.69) and height (-3.14 +/- 0.98:-2.00 +/- 0.67). Improved subcutaneous tissue stores were demonstrated by increased thickness of both subscapular skinfolds (change = 71% +/- 26%) and triceps skinfolds (38% +/- 17%). After nutritional intervention, the acute care hospitalization rate, compared with the 2-year period before intervention, decreased from 0.4 +/- 0.18 to 0.15 +/- 0.06 admissions per patient-year and included only 3 admissions (0.02 per patient-year) related to feeding problems., Conclusions: In children with developmental disabilities, diagnosis-specific treatment of feeding disorders results in significantly improved energy consumption and nutritional status. These data also indicate that decreased morbidity (reflected by a lower acute care hospitalization rate) may be related, at least in part, to successful management of feeding problems. Our results emphasize the importance of a structured approach to these problems, and we propose a diagnostic and treatment algorithm for children with developmental disabilities and suspected feeding disorders.children, developmental disabilities, fundoplication, gastroesophageal reflux, gastrostomy, hospitalization, nutrition.

Background: Nonspecific esophageal motility disorders (NEMDs) have been identified in up to 50% of adults with noncardiac chest pain or dysphagia. This study sought to determine the incidence of NEMDs in children with upper gastrointestinal tract symptoms and to evaluate the clinical course of pediatric patients with these manometric abnormalities., Methods: The study involved 154 children aged 4 to 18 years (mean age, 11.6+/-2.6 years [SE]) who had upper gastrointestinal, swallowing-related symptoms. The children were evaluated by 24-hour intraesophageal pH monitoring, esophageal manometry, and esophagogastroduodenoscopy., Results: Gastroesophageal reflux (GER) was diagnosed by pH study in 109 (71%) of 154 patients, and examination of biopsy specimens demonstrated esophagitis in 70 children with GER. Results of esophageal manometry were abnormal in 30 (67%) of 45 children without GER. A variety of motility disorders were diagnosed in 17 of the patients without GER, whereas NEMDs were diagnosed in the remaining 13 children (mean age, 10.6+/-2.7 years; 10 boys, 3 girls). Patients with GER showed normal esophageal wave propagation; however, mean lower esophageal sphincter pressure was significantly lower in patients with GER than in children with NEMDs. The children with NEMDs exhibited a diverse array of symptoms, including esophageal food impaction in 4 of the 13 patients. During a 36.2+/-4.3-month follow-up period, no correlation was found between therapeutic intervention and clinical course in the 13 patients with NEMDs. Symptomatic improvement occurred in 6 of 13 patients, including 3 children for whom no pharmacologic therapy was prescribed., Conclusions: These data indicate that NEMDs represent a common group of esophageal manometric abnormalities in children with upper gastrointestinal tract symptoms and without GER. Food impaction appears to be a relatively frequent complication, and NEMDs should be considered in children who have this finding.

We describe a pediatric patient with dyskeratosis congenita, whose symptoms included abdominal pain, vomiting, dysphagia, and hematochezia. Gastrointestinal symptom are prominent in this rare genetic disorder.

Investigations of the cytoskeleton in mammalian eggs and embryos have revealed the existence of an unusual array of crosslinked intermediate filaments composed of cytokeratins 5, 6, 16, and 'Z' that are referred to as cytoskeletal sheets. We have been investigating the function of these cytoskeletal sheets during embryogenesis. In this investigation we report the rapid appearance of extensive arrays of tonofilaments extending across blastomeres and in association with intercellular desmosomal junctions appearing at the time the embryo hatches from its zona pellucida, through the time of implantation of the embryo into the uterine wall. Just prior to the time of gastrulation these tonofilaments disappear. Electron microscopy and immunoconfocal microscopy demonstrate that the tonofilaments are composed of cytokeratins characteristic of the type found earlier in development, that is types 5 and 6; whereas, cytokeratin type 8 which has been shown to be synthesized in blastocysts is localized primarily at perinuclear regions. Cytokeratins 8 and 18 are synthesized to about the same extent as actin at the time the tonofilaments appear whereas the synthesis of cytokeratins 5 and 6 is greatly reduced. Our results suggest that cytokeratins 5 and 6 in the tonofilaments may arise from the stored form of cytokeratins in the cytoskeletal sheets. Consequently, our results suggest that the sheets may serve as a maternal reserve of cytokeratin employed by the embryo at the time of implantation to form extensive arrays of tonofilaments in the embryo that likely provide structural integrity to the embryo as it is subjected to mechanical stress during invasion and implantation into the uterine wall.

Objective: To determine the importance of acid reflux-induced dysmotility in the genesis of noncardiac chest pain in children., Method: We performed esophageal manometries during intraesophageal perfusion with 0.9% NaCl or 0.1 N HCl in 19 children (age, 14.5 +/- 0.5 yr) with gastroesophageal reflux, biopsy-proven esophagitis, and complaints of at least one episode of chest pain per day., Results: Baseline esophageal motilities were normal in all patients. Eight of 19 children (42%) complained of chest pain during intraesophageal acid perfusion. In three of these eight patients, complaints of chest pain during acid perfusion were temporally associated with "conversion" of previously normal motility patterns to manometric tracings, indicating esophageal dysmotility. Compared with findings during saline perfusion, esophageal acid exposure in these three children resulted in significant increases in both the duration (13.6 +/- 4.0 vs 3.2 +/- 0.2 s, p < 0.05) and amplitude (105.2 +/- 7.8 vs 61.2 +/- 2.1 mm Hg, p < 0.05) of esophageal contractions during wet swallows. Symptoms of chest pain resolved in all patients after therapy with H2-receptor antagonists., Conclusions: These data represent the first demonstration of acid-induced esophageal dysmotility in children with chest pain and suggest that reflux-induced motor abnormalities contribute to the onset and/or exacerbation of chest pain in pediatric patients with gastroesophageal reflux and esophagitis.

To determine whether obesity should be added to the current American Academy of Pediatrics (AAP) criteria for cholesterol screening in childhood, the charts of 99 children referred for evaluation of either hypercholesterolemia (n = 53) or obesity (n = 45) were reviewed. Compared with obese children, nonobese hypercholesterolemic subjects were younger (8.4 vs 11.4 years) and had lower mean body mass index and % ideal body weight. Frequency of elevated (> 90th percentile for age) total and low-density lipoprotein cholesterols were similar in both groups. Fifty-three of 65 children who met the current AAP criteria were hypercholesterolemic, however, 23/76 hypercholesterolemic children failed to satisfy these screening criteria. Thirty-six of 45 obese children had cholesterol levels > 90th percentile, suggesting increased risk for hypercholesterolemia in this group. If obesity was added to the AAP criteria, 66/80 hypercholesterolemic subjects would have been identified. These modified criteria, vs AAP standards, significantly improved both their sensitivity (70 vs 87%, p < 0.02) and negative predictive value (45 vs 30%, p < 0.02). Pending further studies in larger pediatric populations, these data indicate that obesity should be considered a risk factor for hypercholesterolemia in childhood, and we recommend modifying the AAP screening criteria to include obese children.

The relationship between gastric Helicobacter pylori colonization and esophagitis was determined in 457 children undergoing endoscopic evaluation of abdominal pain and/or vomiting. In all patients, biopsies of the esophagus were examined histologically, and two antral biopsies were analyzed for the presence of H. pylori, using standard microbiological and histochemical techniques. The incidence of biopsy-proven esophagitis was similar in H. pylori-positive (15/56 patients) and -negative (94/401; p = NS) groups. Clinical improvement, after 2 months of antisecretory therapy with H2-receptor antagonists, was independent of H. pylori status (11/15 vs. 68/94 responders; p = NS). All 26 H. pylori-negative nonresponders became asymptomatic with a second course of H2-blockers. The 4/15 H. pylori-positive patients (all of whom had associated gastritis/duodenitis) who failed antisecretory therapy responded clinically to treatment with amoxicillin plus bismuth subsalicylate. These data indicate that primary treatment of biopsy-confirmed esophagitis in children should include anti-secretory agents, regardless of H. pylori status. A small percentage of H. pylori-positive patients with esophagitis and concomitant gastroduodenal inflammation may require additional antibacterial therapy, suggesting that presence of the organism should be assessed in all pediatric patients undergoing upper endoscopic evaluation.

We investigated the signal transduction pathways that mediate activation of Syrian hamster eggs. Under conditions in which the concentration of intracellular free calcium ([Ca2+]i) is clamped low, activation of protein kinase C (PKC) can induce second polar body formation, reformation of the nuclear envelope, and decondensation of chromatin, as well as golgi reformation. However, calcium is necessary for normal transition from meiotic metaphase II to anaphase II. Conversely, under conditions in which the level of PKC activity is clamped low, induction of a rise in [Ca2+]i, using the calcium ionophore A23187, does not induce egg activation. These results strongly suggest that PKC acts after the calcium signal as a proximal inducer of egg activation. This suggestion is supported by the kinetics of egg activation; PKC stimulators activate the eggs at a significantly enhanced rate (P < 0.01) compared with activation by calcium ionophore. We show here that PKC stimulators induce emission of the second polar body, but that subsequently, with longer culture, the emitted polar body is absorbed. Our results suggest that the rise in [Ca2+]i serves two functions, to activate PKC and to induce the transition from metaphase II to anaphase II. PKC, once activated, mediates several other events of egg activation.

To evaluate the relationship between colonic methane production and carbohydrate malabsorption, we measured end-expiratory methane levels in 70 normal and 40 lactose-intolerant children. Time-dependent excretion of hydrogen and methane was determined every 30 min for 120 min following a fasting oral lactose challenge (2 g/kg). Mean breath hydrogen levels in normals (lactose-tolerant) equaled 3.7 parts per million (ppm) throughout the study, but increased to > 10 ppm by 60 min and remained elevated in lactose-intolerant subjects. Breath methane in normal children averaged 1.6 ppm from 0 to 120 min. In contrast, CH4 excretion by lactose-intolerant children averaged 5.1 ppm at 90 min; and, by 120 min levels increased significantly compared with control. Breath methane levels in lactose-intolerant subjects following a lactose load continued to increase, however, despite the coingestion of exogenous lactase in amounts calculated to result in complete hydrolysis of the disaccharide. These data demonstrate that lactase-deficient children manifest significant increases in breath methane excretion following lactose ingestion and that enhanced methane production may be a consequence of several factors, including altered fecal pH and increased methanogenic substrates provided by colonic lactose fermentation. Further studies are required to determine the clinical significance of elevated methane production in lactose intolerance.

To determine the effect of altered membrane fluidity on platelet aggregation/agglutination, fresh, washed human platelets were treated with A2C, a cyclopropyl fatty acid ester which is known to enhance mobility of intrinsic membrane bilayer constituents and increase membrane fluidity. Fluorescence polarization studies demonstrated A2C incubation time- and concentration-dependent increases in platelet membrane fluidity (decreased fluorescence anisotropy). Preincubation with A2C was associated with diminished collagen, thrombin and ristocetin-induced platelet aggregation/agglutination. Aggregation/agglutination was diminished by 93 +/- 5% for collagen (0.2 mg/ml), 53 +/- 3% for thrombin (1.0 U/ml) and 85 +/- 9% for ristocetin (1.1 mg/ml). These data suggest that membrane fluidity is involved in the regulation of platelet function.

The charts of 54 children diagnosed with antral H. pylori were reviewed, to establish the incidence of gastroduodenal inflammation and compare therapeutic efficacies of antisecretory vs. antibacterial therapy. Histology demonstrated normal mucosa in three cases (6%) and gastric/duodenal inflammation (> or = Whitehead grade 3) in 51 biopsies (94%). 23/43 children (53%) initially responded to H2-blockers; however, by 10 mo, 13 had relapsed clinically. All of these patients subsequently responded to amoxicillin plus bismuth subsalicylate. Of the 20 children who failed to enter remission after an initial course of H2-blockers, all became symptom-free after treatment with amoxicillin/bismuth. Compared to antisecretory agents, antibacterial treatment induced clinical remission in 11/11 patients (p < 0.001), who remained symptom-free for 10 +/- 0.2 mo. Clinical remissions were maintained in significantly more patients following amoxicillin/bismuth vs. H2-blockers (44/54 vs. 10/43 courses, p < 0.001); and, the cumulative probability of remaining asymptomatic was significantly greater in the antibiotic group (p < 0.001). These data suggest that gastric colonization by H. pylori is highly predictive of mucosal pathology in children. Initial therapy should be directed toward achieving bacterial eradication, as opposed to gastric acid suppression.

Basolateral membranes from rabbit proximal colon were prepared from isolated colonocytes throughout postnatal maturation, using a modification of published techniques. In suckling (14-20 day) and post-weaning/mature (35-49 day) animals, membranes were purified approx. 10-fold, based upon the enrichment of ouabain-sensitive, sodium-potassium dependent adenosine triphosphatase activity. Membrane lipid analyses demonstrated age-dependent increases in total cholesterol and the cholesterol/phospholipid molar ratio, as well as decreases in phosphatidylethanolamine content and the fatty acid unsaturation index. Fluidity of basolateral membranes and membrane liposomes, determined from fluorescence anisotropy measurements using the lipid probes 1,6-diphenyl-1,3,5-hexatriene and DL-12-(9-anthroyl)stearic acid, demonstrated significant, ontogenic decreases in fluidity; and, additional studies showed that fluidity changes occurred early in the weaning period (by day 24 postnatally). Arrhenius plots of liposome anisotropies suggested a bilayer lipid thermotropic transition temperature of 22 degrees C in sucklings 26 degrees C in mature rabbits. These findings demonstrate that ontogeny of colonic basolateral membranes is associated with significant modulations in lipid composition and fluidity.