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Paneth cell metaplasia of the rectal epithelium is a common histologic finding in patients with chronic inflammatory bowel disease. However, the clinical significance of isolated Paneth cells in otherwise unremarkable rectal mucosa has not been extensively examined. This study examined the frequency and clinical correlates of rectal Paneth cells in 245 biopsies obtained from patients between the ages of 2 weeks to 20 years in a pediatric tertiary care facility from 2010 to 2011. The specimens comprised 193 endoscopic pinch biopsies and 52 rectal suction biopsies. All 245 cases were endoscopically and histologically unremarkable with no prominence of eosinophils, no altered mucosal architecture, and no inflammation. Paneth cells were present in 42 cases (17.1%), which is higher than previous reports. Only 1 of 42 patients with rectal Paneth cells was subsequently diagnosed with Crohn disease. In our study population, the finding of Paneth cells was associated with young age, and the incidence of Paneth cell cases decreased with increasing age (χ=13.69, P=0.0002). Constipation was the most common presenting symptom in patients with rectal Paneth cells and was highly associated with the presence of Paneth cells (odds ratio 4.5, 95% confidence interval: 2.2-9.0). Paneth cells in otherwise unremarkable pediatric rectal biopsies are not rare and frequently occur in common conditions such as idiopathic constipation.

Paneth cells have been reported in colorectal ad- enomas and adenocarcinomas; however, the frequency of co- lonic Paneth cell-containing adenomas is unknown as are their clinicopathologic features. A total of 152 consecutive colorectal adenomas from 103 patients (57 males and 46 females) were reviewed. The frequency of Paneth cells in this cohort of ad- enomas was determined and correlated with patient demo- graphics. Twenty-six adenomas (17.1%) from 22 (21.4%) patients harbored Paneth cells, which were not limited to the base of the crypts but aberrantly located throughout the crypts. Patient age, adenoma size, villous features, and grade of dys- plasia were not different between these 2 groups. Not surpris- ingly, Paneth cell-containing adenomas were more likely to occur in the proximal colon (84.6% vs. 55.6%; P = 0.006). There was a strong association between male sex and Paneth cell-containing adenomas, as 23 of 26 (88.5%) of these ad- enomas occurred in male individuals compared with 71 of 126 (56.3%) non-Paneth cell-containing adenomas (P = 0.002). Upon review of an additional 460 adenomas from 200 patients with varying numbers of adenomas (68 with 1 adenoma, 68 with 2 adenomas, and 64 with 3 or more adenomas), the risk of harboring synchronous adenomas was associated with villous morphology, proximal location, and the presence of a Paneth cell-containing adenoma. Thus, the presence of a Paneth cell- containing adenoma may be a marker for increased risk of de- veloping colorectal neoplasia.

Purpose of review To review recently published studies presenting novel and relevant information on Paneth cells and their function. Recent findings Paneth cells are secretory epithelial cells which are predominantly found in the small-intestinal crypts of Lieberkuhn. Their most abundant products are alpha-defensins, which are endogenous antibiotics with activity against gram-negative and gram-positive bacteria, fungi, viruses and protozoa. The differentiation from stem-cell progenitors to Paneth cells is regulated by Wnt signalling via a complex gene programme, terminally including defensins. A disturbance of Paneth-cell differentiation and function may predispose to intestinal infections and appears to be a critical factor in the pathogenesis of ileal Crohn's disease, an inflammatory disease of the intestinal tract. Summary It is conceivable that these recent findings together with a better understanding of underlying mechanisms involved in the regulation and biology of Paneth cells will open up new therapeutic avenues for preventing infection as well as for causally treating inflammatory bowel diseases.

Paneth cell-like change (PCLC) of the prostatic glandular epithelium was focally observed in one case of normal glandular epithelium, two cases of glandular and stromal hyperplasia, one case of prostatic intraepithelial neoplasia, and four cases of prostatic adenocarcinoma. The distinctive cells were characterized by bright, eosinophilic cytoplasmic granules on routine hematoxylin and eosin-stained material. The cytoplasmic granules in the benign prostatic epithelium were periodate-Schiff's procedure (PAS)-positive and diastase resistant and immunohistochemically negative for lysozyme, neuron-specific enolase, chromogranin, and serotonin. The eosinophilic granules in the prostatic intraepithelial neoplasia and adenocarcinoma cases were immunohistochemically positive for chromogranin, serotonin, and neuron-specific enolase, and negative for lysozyme. By electron microscopy the eosinophilic granules represented exocrine-like or lysosomal-like vesicles in the benign epithelium and neuro-endocrine granules in the malignant epithelium. The lesion represents a prostatic epithelial PCLC rather than a Paneth cell metaplasia. PCLC is the common histological manifestation of two different phenomena: (a) a PAS-positive and diastase-resistant eosinophilic cytoplasmic granular change in benign prostatic epithelium, and (b) endocrine differentiation with neuroendocrine granules in dysplastic and malignant prostatic epithelia. The importance of recognizing PCLC lies in its differentiation from other possible prostatic cytoplasmic inclusions.

We present an unusual variant of prostatic adenocarcinoma with obvious mucinous and neuroendocrine features, arising in the transition zone. The neuroendocrine component is largely represented by Paneth-like cells (PLCs). These cells correspond to previously described eosinophilic cells and are amphicrine. We could demonstrate immunohistochemically the presence of calcitonin in some of these PLCs. The prognostic significance of these special characteristics is not well known, but it is most likely that this type of prostate cancer will not respond well to hormonal therapy.

Objectives: How alcohol consumption affects the integrity and the defense mechanisms of the mucosa in the upper gastrointestinal tract is largely unknown. We examined the effect of heavy alcohol use on gastric and duodenal Paneth-cell-derived and epithelial antimicrobial peptides (AMPs), cytokines, and the Wnt pathway, an important regulator of epithelial regeneration. Methods: In 22 patients with heavy alcohol use and 17 control subjects, biopsies from gastric corpus, antrum, and duodenum were examined for messenger RNA (mRNA) of AMPs, cytokines, and Wnt pathway factors using real-time PCR. The expression of the α-defensin HD5 was analyzed immunohistochemically. The effect of alcohol exposure on Wnt signaling and AMP production was also studied in a gastric cell line using mRNA and reporter gene assays. Results: Heavy alcohol use was associated with increased expression of Paneth cell HD5 and HD6 mRNA in the antrum, where these products are normally absent (HD5 mRNA in controls vs. patients: 2100±900 and 365 500±161 600, HD6 mRNA: 320±130 and 58 300±32 600 copies per 10 ng total RNA, means±s.e.m., P value: 0.022 and 0.011). Upregulated HD5 was independent of intestinal metaplasia that was observed in a minority of patients. No significant differences were found for β-defensins and cytokines (interleukins IL1β, IL6, IL8, IL10). In patients, Wnt pathway factors showed a trend toward higher levels. In vitro, ethanol exposure induced the production of HD5 and HD6 and activation of the Wnt pathway. Conclusions: Alcohol exposure can induce gastric Paneth cell AMP expression. This may be linked to Wnt pathway activation, which has an important role in the epithelial regenerative homeostasis.

We have previously shown a reduction of gastrointestinal symptoms after the oral administration of Bifidobacterium infantis Natren Life Start super strain (NLS-SS) in untreated celiac disease (CD) patients. The symptomatic improvement was not associated with changes in intestinal permeability or serum levels of cytokines, chemokines, or growth factors. Therefore, we hypothesized that the beneficial symptomatic effect observed previously in patients with CD treated with B. infantis may be related to the modulation of innate immunity. To investigate the potential mechanisms of a probiotic B. infantis Natren Life Start super strain on the mucosal expression of innate immune markers in adult patients with active untreated CD compared with those treated with B. infantis×6 weeks and after 1 year of gluten-free diet (GFD). Numbers of macrophages and Paneth cells and α-defensin-5 expression were assessed by immunohistochemistry in duodenal biopsies. We showed that GFD decreases duodenal macrophage counts in CD patients more effectively than B. infantis. In contrast, B. infantis decreases Paneth cell counts and expression of α-defensin-5 in CD (P

INTRODUCTION Sepsis is a life-threatening syndrome which can progress to multiple organ dysfunction with high mortality. Intestinal barrier failure exerts a central role in the pathophysiological sequence of events that lead from sepsis to multiple organ dysfunction. The present study investigated the role of hydrocortisone (HC) administration and fecal microbiota transplantation (FMT) in several parameters of the gut barrier integrity, immune activation, and survival, in a model of polymicrobial sepsis in rats. METHODS Forty adults male Wistar rats were randomly divided into four groups: sham (group I), cecal ligation and puncture (CLP) (group II), CLP + HC (2.8 mg/kg, intraperitoneally single dose at 6 h) (group III), and CLP + FMT at 6 h (group IV). At 24 h post-CLP, ileal tissues were harvested for histological and immunohistochemical analyses while endotoxin, IL-6, and IL-10 levels in systemic circulation were determined. In a second experiment the same groups were observed for 7 days for mortality, with daily administration of hydrocortisone (group III) and FMT (group IV) in surviving rats. RESULTS HC administration and FMT significantly reduced mortality of septic rats by 50%. These interventions totally reversed intestinal mucosal atrophy by increasing villous density and mucosal thickness (μm, mean ± SD: Group I: 620 ± 35, Group II: 411 ± 52, Group III: 622 ± 19, Group IV: 617 ± 44). HC and FMT reduced the apoptotic body count in intestinal crypts whereas these increased the mitotic/apoptotic index. Activated caspase-3 expression in intestinal crypts was significantly reduced by HC or FMT (activated caspase-3 (+) enterocytes/10 crypts, mean ± SD: Group I: 1.6 ± 0.5, Group II: 5.8 ± 2.4, Group III: 3.6 ± 0.9, Group IV: 2.3 ± 0.6). Both treatments increased Paneth cell count and decreased intraepithelial CD3(+) T lymphocytes and inflammatory infiltration of lamina propria to control levels. In the sham group almost the total of intestinal epithelial cells expressed occludin (92 ± 8%) and claudin-1 (98 ± 4%) and CLP reduced this expression to 34 ± 12% for occludin and 35 ± 7% for claudin-1. Administration of HC significantly increased occludin (51 ± 17%) and claudin-1 (77 ± 9%) expression. FMT exerted also a significant restoring effect in tight junction by increasing occludin (56 ± 15%) and claudin-1 (84 ± 7%) expression. The beneficial effects of these treatments on gut barrier function led to significant reduction of systemic endotoxemia (EU/mL, mean ± SD: Group I: 0.93 ± 0.36, Group II: 2.14 ± 1.74, Group III: 1.48 ± 0.53, Group IV: 1.61 ± 0.58), while FMT additionally decreased IL-6 and IL-10 levels. CONCLUSION Fecal microbiota transplantation and stress dose hydrocortisone administration in septic rats induce a multifactorial improvement of the gut mechanical and immunological barriers, preventing endotoxemia and leading to improved survival.

Programmed cell death protein 1 (PD-1) blocking agents are novel immunotherapeutics used for treatment of advanced-stage malignancies. They have shown promise in the treatment of several malignancies, with greater efficacy and better tolerability than cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking agents. However, as with anti-CTLA-4 agents, clinically significant colitis remains an important complication. Although there is growing awareness of the histopathologic features of anti-CTLA-4 therapy, there is little information on the pathologic features of anti-PD-1 colitis. We describe here the histopathologic findings in 8 patients who developed colitis while on anti-PD-1 monotherapy. The most common pattern of injury observed (5/8 cases) was an active colitis with neutrophilic crypt microabscesses and with prominent crypt epithelial cell apoptosis and crypt atrophy/dropout. These latter features are reminiscent of other colitides with prominent apoptosis such as acute graft-versus-host disease or certain drug-induced colitides. The remainder of cases (3/8) showed a lymphocytic colitis-like pattern, characterized by increased intraepithelial lymphocytes and surface epithelial injury. Apoptosis was also often increased in these cases but crypt atrophy/dropout was not present. In patients who experienced recurrence of anti-PD-1 colitis, histologic features were similar to the initial insult but, in addition, features of chronicity developed that mimicked inflammatory bowel disease (basal lymphoplasmacytosis and crypt architectural irregularity, and Paneth cell metaplasia in 1 case). Awareness of the clinical scenario, however, should allow pathologists to suggest anti-PD-1 colitis. Interestingly, recurrent colitis was observed in patients who had been off anti-PD-1 therapy for many months. As anti-PD-1 agents are increasingly used in oncology, we present this series to increase awareness of anti-PD-1 colitis among pathologists, to facilitate its timely diagnosis and treatment.

The purpose of this study is to provide an overview of the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in inflammatory bowel disease (IBD).Human genetic studies have identified several UPR-related genes and autophagy-related genes as IBD risk loci. Impairment of each branch of the UPR causes spontaneous enteritis or creates higher susceptibility for intestinal inflammation in model systems. Deficiency of either UPR or autophagy in small intestinal epithelial cells promotes each other's compensatory engagement, which is especially prominent in Paneth cells such that, in the absence of both, severe spontaneous enteritis emerges.Interactions between the UPR and autophagy exhibit critical synergistic interactions within the intestinal epithelium and especially Paneth cells that are of considerable importance to the maintenance of homeostasis. When dysfunctional in the Paneth cell, spontaneous inflammation can emerge that may extend beyond the epithelium providing direct experimental evidence that subsets of Crohn's disease may emanate from primary Paneth cell disturbances.

This article reviews the most recent publications on innate immunity in the small intestine. We will go over the innate immune receptors that act as sensors of microbial presence or cell injury, Paneth cells as the main epithelial cell type that secrete antimicrobial peptides, and mucosal production of immunoglobulin A (IgA). In addition, we will give an update on examples of imbalance of the innate immune response resulting in clinical disease with the most relevant example being Crohn's disease.Toll-like receptors (TLRs) are involved in B-cell homing to the intestine, rejection of small intestinal allografts, and recruitment of mast cells. The TLR adaptor Toll/interleukin-1 receptor domain-containing adapter-inducing interferon-β is necessary to activate innate immunity after Yersinia enterocolitica infection. Moreover, MyD88 is required to keep the intestinal microbiota under control and physically separated from the epithelium, and RegIIIγ is responsible for the bacterial segregation from the lining epithelial cells. In Crohn's disease, ATG16L1 T300A variant promotes a proinflammatory response; and miR-196 downregulates a protective immunity-related GTPase family M protein (IRGM) polymorphism leading to impaired clearance of adherent Escherichia coli in the intestine.The intestine is continuously exposed to dietary and microbial antigens. The host has to maintain intestinal homeostasis to keep the commensal and pathogenic bacteria under control. Some of the mechanisms to do so are by expression of innate immune receptors, production of antimicrobial peptides, secretion of IgA, or autophagy of intracellular bacteria. Unfortunately, in some cases the innate immune response fails to protect the host and chronic inflammation, transplant rejection, or other disorders may occur.

Details of 12 patients suffering from atrophy of the coeliac mucosa (ACM) are presented. These patients failed to respond to the elimination of gluten from their diets. Their jejunal biopsies were examined in detail with particular attention given to Paneth cell numbers, crypt length, mitotic rate and mucosal thickness. These biopsies were compared with the biopsies of responsive coeliac patients. The ACM patients were found to have a statistically significant reduction in Paneth cell numbers (P < 0.0005), reduced crypt length (P < 0.0125), reduced mitotic rate (P < 0.0005) and a thinner mucosa (P < 0.0005), when compared with the responsive coeliac group. In addition the ACM group had a lower albumin level compared with the responsive group (P < 0.0005). Most of the ACM patients responded when treated with oral corticosteroids. It is considered that the above features are markers of a non-responsive group of coeliac patients and thus might be useful for identifying those patients who may benefit from early treatment with oral corticosteroids if gluten withdrawal is not rapidly effective.

Burn injury often leads to distant organ injury such as acute respiratory distress syndrome. We hypothesize that the pathophysiologic changes in distant organs result from orchestrated regulation of multiple genes in response to burn injury. Differential display was performed to identify genes regulated in distant organs in response to burn injury. Initial characterization of differentially amplified products demonstrated that HAX-1s mRNA was regulated in several distant organs after 18% total body surface area (TBSA) full-thickness flame burn injury in mice. Further characterization of HAX-1s mRNA revealed a novel transcript variant, which is rapidly and transiently induced in multiple tissues of mice within 6 h after burn injury. This novel HAX-1s transcript variant, called HAX-1xs, has an internal deletion of 252 nucleotides and single point mutation, resulting in reading frame intact. Western blot and immunohistochemical analyses of multiple tissues of mice using rabbit antibody raised against a 15-mer synthetic peptide clearly revealed the presence of HAX-1xs protein in the duodenum, and suggested that expression of HAX-1xs and/or HAX-1s was tissue- and cell type-specific. The expression of HAX-1xs and/or HAX-1s was distinctively regulated in Paneth cells of the duodenum and macrophages of the thymus after burn injury. These findings suggest that HAX-1xs has a different biological activity from HAX-1s and participates in a cascade of immediate-early cellular events in response to burn injury. KEYWORDS—HAX-1s, HAX-1xs, burn injury, Paneth cell, thymus, mice

Recently published studies presenting novel and relevant information on defensins and other antimicrobial peptides in Crohn's disease and ulcerative colitis are reviewed.Different clinical localizations of Crohn's disease are associated with different deficiencies in epithelial and leukocyte antimicrobial peptide expression. As compared with ulcerative colitis, Crohn's disease of the colon is characterized by an impaired induction of beta defensins, and antimicrobial antiproteases elafin and SLPI, as well as the cathelicidin LL37. The attenuated induction of beta defensins is linked to fewer gene copy numbers in this locus, which is associated with colonic but not ileal Crohn's disease. In contrast, ileal Crohn's disease patients are characterized by a reduced antibacterial activity and a specific reduction of ileal Paneth cell defensins. This decrease is independent of the grade of histological inflammation and cannot be found in inflammation controls. Thus, some of these defects can be explained either by direct or indirect genetic mechanisms and appear to be primary.Unlike ulcerative colitis, ileal and colonic Crohn's disease are characterized by localized deficiencies of antibacterial peptides. Understanding the precise molecular mechanisms of the defective antibacterial barrier function might provide new therapeutic directions.

Objectives: Bowel segments distal to a congenital intestinal obstruction have been suggested to be immature. In other words, luminal components such as amniotic fluid (before birth) and/or enteral nutrition (after birth) may be required to activate intestinal epithelial protein expression, thereby influencing epithelial differentiation. We investigated cell-type–specific protein expression proximal and distal to jejunal and ileal atresias in human newborns. Patients and Methods: We immunohistochemically studied intestinal tissue specimens of 16 newborns who had undergone surgery for jejunal or ileal atresia. Sections were taken from both the proximal and distal sides of the atresias. Results: For all patients, the enterocyte-specific markers lactase, sucrase-isomaltase, sodium glucose cotransporter 1, glucose transporters 2 and 5, intestinal fatty acid–binding protein and alkaline phosphatase were expressed at a mean 3 ± 1 days after birth, both proximal and distal to jejunal and ileal atresias. Expression of goblet cell–specific markers mucin 2 and trefoil factor 3 and that of the Paneth cell marker lysozyme was maintained at either side of the atretic segment. Conclusions: With respect to the markers used, the human small intestinal epithelium is already differentiated shortly after birth. The absence of intestinal continuity in case of a jejunal or ileal atresia does not affect epithelial protein expression. This would seem to indicate that the developing small intestinal epithelium matures independently of luminal components.

Survival for the extremely low gestational age neonate (ELGAN; 24-28 weeks) has risen to more than 80%. This extraordinary achievement is tempered by the persistence of cognitive delays and cerebral palsy (CP) affecting nearly one in eight survivors, and requiring subsequent rehabilitative services. A major priority in newborn medicine must be to translate the gains in survival achieved over the past 40 years into gains in healthy survival without the current high frequency of impairments.Transient hypothyroxinemia in ELGANs is strongly associated with lower IQ scores, behavioral abnormalities and CP. Limited evidence suggests the possibility of a benefit from hormone replacement therapy, but the optimal trial has yet to be conducted. A continuous infusion of 4 μg/kg per day thyroxine for 42 days can safely correct transient hypothyroxinemia without markedly lowering thyroid stimulating hormone levels, thus creating a biochemical euthyroid state. Whether this treatment will make an impact on long-term outcomes is not yet known.With 25 000 neonates born in less than 28 weeks each year in the USA, the economic impact of the very high rates of cognitive disabilities and related neurological dysfunction in survivors is substantial. The lifetime direct and indirect costs of CP are estimated at US$1 million per person and the costs of mental retardation are even higher. If reversal of transient hypothyroxinemia proves effective in reducing the risks of CP or mental retardation in ELGANs by 30%, we estimate an overall saving of US$ 3 billion per year. There is a pressing need for a phase III trial of thyroid hormone that is of sufficient duration and size to determine whether a clinically important reduction in risk of developmental impairments in ELGANs can be achieved.

OBJECTIVE To determine in low birth weight infants the relations of being small for gestational age at birth, microcephalic at birth, low weight for age at 2 years, and microcephalic at 2 years to full scale intelligence quotient (FSIQ) at the age of 16 years. METHODS A prospective observational study of 422 of 837 eligible nondisabled low birth weight (

BACKGROUND With the exception of fungi, microbial infections are rare in the oesophagus. Herein, we aimed to systematically assess the distribution and quantity of different antimicrobial host factors as well as, for the first time, functional mucosal antimicrobial activity in the upper gastrointestinal tract. METHODS We investigated biopsies from the healthy oesophagus, three different locations in the stomach and the duodenum in a total of 12 individuals. Using real-time PCR with external standards, we compared absolute expression of mRNA encoding antimicrobial peptides including defensins, cathelicidin, bactericidal/permeability-increasing protein, psoriasin, and elafin. In addition, we performed immunostaining for human-beta-defensin-1 (HBD1), elafin, and psoriasin. To test functional relevance, we assessed antimicrobial as well as antifungal activity of cationic extracts from biopsies against E. coli ATCC 25922 and a clinical isolate of Candida albicans. RESULTS In contrast to HBD1 which was similarly expressed in all tissues, inducible beta-defensins in the healthy oesophagus were much higher compared with the stomach and duodenum (for HBD2-4: P

Cerebral palsy (CP) is a diagnosis of considerable concern to obstetricians, but the diagnosis of CP can be challenging, and may need to be confirmed by an experienced practitioner, ideally a child neurologist or psychiatrist. It is important not to make the diagnosis too early in infancy, especially when the signs are not severe, as resolution of early neuromotor abnormalities does occur, particularly in premature infants. Exclusion of genetic/metabolic disorders presenting with CP-like findings is important. The degree of activity limitation should be characterized; labeling children as having CP on the basis of abnormal examination findings alone without evidence of activity limitation is not useful. Brain imaging can be helpful in pinpointing the location of the underlying brain abnormality and sometimes provides etiologically useful information.

OBJECTIVE To investigate whether bacterial translocation is the causative mechanism underlying cytokine production during hemorrhagic shock. DESIGN Prospective, randomized, unblinded animal study. SETTING Surgical research laboratories of Shiga University of Medical Science. SUBJECTS Male Sprague-Dawley rats. INTERVENTIONS The rats were randomly divided into three groups. Each animal was anesthetized with pentobarbital, given a continuous infusion of 0.9% saline, and monitored for blood pressure. The normoxic and sham shock groups breathed room air, whereas the hyperoxic shock group was administered 100% oxygen. Except in the sham shock group, blood was withdrawn to induce a hemorrhagic shock state, then the shed blood was reinfused. Sixty minutes after the induction of hemorrhagic shock, arterial blood cultures were performed in all three groups. The animals were then killed, and their mesenteric lymph nodes (MLNs) were harvested for bacterial culture. The terminal ileum, liver, spleen, kidney, lung, and MLNs were also collected for histologic study by in situ hybridization. MEASUREMENTS AND MAIN RESULTS In the bacteriologic study, the prevalence of bacterial translocation was 0% (0/11) in the hyperoxic shock group, 55% (6/11) in the normoxic shock group, and 0% (0/9) in the sham shock group. In the in situ hybridization study, tumor necrosis factor-alpha gene expression was detected only in the ileal tissue, MLNs, and spleens of the normoxic shock group. Blood cultures were sterile in all three groups. CONCLUSIONS Bacterial translocation occurred in MLNs within 1 hr of hemorrhage. Hemorrhagic shock causes tumor necrosis factor-alpha gene expression as well as bacterial translocation in MLNs, but not in the liver, in this model. Bacterial translocation was prevented by hyperoxia early in the course of hemorrhagic shock. Hyperoxia also prevented tumor necrosis factor-alpha gene expression along the bacterial invasion route.

Survival of extremely low-birth-weight (ELBW) infants weighing less than 1000 g has improved impressively, but as children and adolescents, they continue to have problems in cognition, achievement at school, behavior, and social adaptation. Only recently have survivors from the early era of postneonatal intensive care reached their young adult years. The investigators report a prospective population-based study carried out in Ontario, Canada, that enrolled 166 ELBW subjects weighing 501 to 1000 g at birth who presently were 22 to 25 years of age. The comparison group consisted of 145 normal-birth-weight (NBW) young adults. Face-to-face interviews were conducted without knowledge of the interviewee's status. Complete data were available for 149 of the ELBW participants and 133 of the NBW group at mean ages of 23.3 and 23.6 years, respectively. Neurosensory impairment of various types had been documented in 27% of the ELBW group and 2% of the NBW group. Average total years of education were significantly fewer in the ELBW group (13.9 vs 14.5 years). The proportion of each group who graduated high school was comparable to that for the overall Canadian population, but ELBW subjects were less likely to have completed the advanced course needed for entering the university (36% vs 57%). Half of the 22 ELBW participants with less than a high school education had neurosensory impairments. Approximately 5% could not be enrolled in special resource classes. Males were overrepresented among ELBW participants with the least education, and they were less likely than females to be enrolled in-or graduated from-a college or university. Rates of permanent employment were 48% for ELBW participants and 57% for the NBW group, both figures being comparable to Canadian norms. A higher proportion of the ELBW group was not in school or employed. More of the ELBW group was unemployed because of either chronic illness or permanent disability (46% vs 15%). Overall living arrangements did not differ, and there were no significant group differences, overall or by gender, in marital status. Contrary to what many have expected, a significant majority of young adults in this study who had been ELBW newborn infants have made a generally successful transition from adolescence to young adulthood, even when those with neurosensory impairment are taken into account. Many of them have overcome earlier problems to become functioning members of society. Parents of ELBW children are entitled to hope that, in the longer term, their children will do as well as NBW children.

We studied rates of early neonatal jaundice in 135 consecutive well newborns in relation to feeding practice. Breast-fed infants had significantly (p less than 0.01) higher rates of jaundice than bottle-fed infants. In a subset of breast-fed infants, sugar water intake in the first 3 days of life was significantly and inversely related to estimated volume of breast milk intake on the 4th day (r = -0.35, p less than 0.05). Breast-fed infants with high sugar water intake in the first 3 days, and low breast milk intake on the 4th day, tended to have higher rates of jaundice, but these results were not statistically significant. These data raise the possibility that in breast-fed infants, sugar water intake may reduce the stimulus to nurse, and thereby increase the risk of jaundice.