Evaluation of probiotic treatment in a neonatal animal model

 The clinical use of probiotic agents such as enteral Lactobacillus to enhance intestinal defense against potential luminal pathogens has been tested in vivo; however, an understanding of the mechanisms responsible for the observed protection is lacking. The purpose of this study was to evaluate the effects of Lactobacillus on bacterial translocation (BT) in a neonatal animal model. Newborn New Zealand white rabbit pups were enterally fed a 10% Formulac solution inoculated with or without a 10⁸ suspension of ampicillin-resistant Escherichia coli K1 (E. coli K1A) and/or Lactobacillus casei GG (Lacto GG). Pups received either no bacteria (n = 10), Lacto GG (n = 8), E. coli K1A (n = 26), or a combination of Lacto GG and E. coli K1A (n = 33). On day 3, representative tissue specimens from the mesenteric lymph nodes (MLN), spleen (SPL), and liver (LIV) were aseptically harvested in addition to a small-bowel (SB) sample that was rinsed to remove luminal contents. The specimens were then cultured in organism-specific media. Statistical analysis was by one-way ANOVA with P values less than 0.05 considered significant. Neonatal rabbits receiving Lacto GG-supplemented formula exhibited a 25% decrease (P < 0.05) in small-bowel colonization by E. coli K1A. In addition, Lacto GG decreased the frequency of extraintestinal BT by 46% (P < 0.05), 61% (P < 0.05), and 23%, respectively, in the MLN, SPL, and LIV. We have shown that enterally-administered Lacto GG decreases the frequency of E. coli K1A translocation in a neonatal rabbit model. These results may have significant implications for the treatment of BT and sepsis in the human neonate and provide a model for further studies.     

Effect of growth hormone on bacterial translocation in experimental short-bowel syndrome

Despite the adaptive process triggered in the remaining intestine by massive bowel resection, bacterial translocation (BT) is frequent under these conditions. Several trophic factors, including growth hormone (GH), are involved in the process of adaptation in short-bowel syndrome (SBS). However, the effect of GH on BT has not been investigated experimentally. The aim of this study was to test the hypothesis that GH administration prevents BT in rats with SBS receiving only parental nutrition (PN). Nineteen adult Wistar rats underwent central venous cannulation and were randomly assigned to one of two groups receiving for 10 days two treatment regimes: PN group (n = 10): fasting, all-in-one PN solution (300 ml · kg · 24 h, 280 kcal/kg · 24 h), 80% gut section including ileocecal valve; GH group (n = 9): fasting, same PN regime and resection plus GH 1 mg/kg s.c). At the end of the experiment, the rats were killed and mesenteric lymph nodes (MLN) and samples of systemic and portal blood were obtained and cultured. Several samples of full-thickness jejunal wall were taken for determining cell proliferation index (PCNA) and mucosal thickness. Jejunal mucosal thickness increased by 30% and PCNA index by 35% in GH-treated rats in comparison with those treated with PN alone. However, contrary to our expectations, BT expressed by positive culture of intestinal flora in portal blood, MLN, or systemic blood was found in 60% of PN and 87% of GH animals (P = 0.1). Translocation to the general circulation expressed by the presence of organisms in systemic blood was detected in 0% of PN and 44% of GH rats (P < 0.05). Although exogenous GH improves gut mucosal structure in rats with SBS treated with PN, it seems to increase rather than decrease mucosal permeability to intestinal bacteria.     

Ureaplasma urealyticum colonization and bronchopulmonary dysplasia: a comparative prospective multicentre study

To determine the role of tracheal colonization at birth with Ureaplasma urealyticum and other pathogenic bacteria with regard to the development of bronchopulmonary dysplasia (BPD), 97 premature infants with very low birth weight (<1500 g) were followed prospectively over 30 days in a multicentre study. Of those infants, 35 were colonized with Ureaplasma urealyticum (group Ia), 22 with other pathogenic bacteria (group Ib) and 40 infants with sterile tracheal aspirates served as controls (group II). Colonization with Ureaplasma urealyticum or with pathogenic bacteria independently increased the risk of developing BPD as compared to the controls (OR 2.55; 95% CI [1.11, 5.87]). Among Ureaplasma urealyticum and bacterial colonized infants, duration of mechanical ventilation and oxygen requirement were significantly longer than among controls (P < 0.05); during the interval of 11 to 35 days of life, every additional day of ventilation significantly increased the risk of BPD (OR 1.22; CI [1.12, 1.32]). The rate of oxygen supplementation, which was similar in both groups during the first 2 weeks of life, was significantly higher among the colonized infants at day 21 (0.38 ± 0.18 and 0.39 ± 0.16 vs 0.31 ± 0.13, P < 0.05) and at day 28 (0.38 ± 0.21 and 0.34 ± 0.15 vs 0.28 ± 0.12, P < 0.05). For infants still ventilated at age of 28 days, Ureaplasma urealyticum and bacterial colonization were associated with a significant higher risk for BPD than for uncolonized controls (OR 5.53; [1.27, 24.02]. Association of Ureaplasma urealyticum and of bacterial colonization and BPD was not weakened after adjustments were made in a multivariate analysis for other significant risk factors. Conclusion Ureaplasma urealyticum colonization is as an important risk factor in the development of bronchopulmonary dysplasia as bacterial colonization even after treatment with surfactant. Received: 23 January 1997 and in revised form: 30 December 1997 / Accepted: 5 January 1998     

DPP4 inhibitor reinforces cell junction proteins in mouse model of short bowel syndrome

Bacterial overgrowth commonly occurs and favors bacterial translocation in short bowel syndrome (SBS). Glucagon-like peptide-2 (GLP-2) is effective for treating SBS, but is rapidly inactivated by dipeptidyl peptidase IV (DPP4). DPP4 inhibitor (DPP4I) is known to be effective for treating SBS. Here, we investigated cell junction protein function following DPP4I administration in a mouse model of SBS. Mice were divided into four groups: naïve (n = 5), naïve + DPP4I (n = 6), control (n = 6), and DPP4I (n = 5). All control and DPP4I mice had 50% of their proximal small bowel resected. DPP4I or normal saline was administered orally twice daily from days 1–7 postoperatively. The functions of cell junction proteins were assessed by RT-PCR and immunohistochemistry. Body weights and blood glucose levels were recorded. E-Cadherin was significantly higher in the DPP4I group than in the control group. E-Cadherin, occludin, and claudin-4 were significantly higher in the naïve group than in the control group. Positive staining for E-cadherin and occludin varied widely between the control and DPP4I groups. Up-regulation of E-cadherin and occludin by DPP4I may be correlated with the anti-inflammatory action of DPP4I. Therefore, DPP4I may reduce bacterial translocation in SBS.     

The effects of mesenteric ischemia on ileal colonization, intestinal integrity, and bacterial translocation in newborn piglets

The effects of mesenteric ischemia on ileal colonization, intestinal integrity, and bacterial translocation (BT) in newborn piglets were investigated in 36-2-day-old Pietrain piglets. Group I, controls were not operated upon; group II underwent a sham laparotomy; and group III underwent ligation of the mesenteric vessels in the distal ileum. After 3 days, the kidneys, spleens, livers, and ileal segments were harvested for microbial and histologic analyses. Two piglets in the ischemic group died; microscopic examination showed severe histologic lesions of the ischemic area. Escherichia coli counts were increased in the ischemic segment compared to the upper loop (P < 0.05). Ischemia favoured staphylococcal colonization, whereas in the sham group a drastic reduction of these organisms was observed (P < 0.005). BT to the kidneys, spleen, and liver occurred normally in the control group. Ischemia significantly increased the total microflora in the spleen and liver (P < 0.05) and furthered dissemination of Clostridium perfringens in the kidneys (P < 0.05); 50% of ischemic animals had proteolytic clostridia in this organ (P < 0.05). Moreover, the incidence of E. coli in the kidneys, spleen, and liver was significantly higher in the sham and ischemic groups than in the controls (P < 0.05). Ileal ischemia thus induced significant histologic lesions, and surgery rather than gut microflora controls translocation. Accepted: 16 November 2000     

The effects of sucralfate and selective intestinal decontamination on bacterial translocation

Sucralfate is widely used as a cytoprotective agent in patients with peptic ulcer and other intestinal mucosal damage. In this study, the effects of sucralfate and/or selective intestinal decontamination with gentamycin on bacterial translocation (BT) in rats with experimentally-induced mechanical jaundice were investigated. Seventy-five adult male Wistar albino rats were divided into five groups of 15 each. In all except a sham group, we performed ligation of the common bile duct (CBD) via a vertical laparatomy. After surgery, the rats in group 1 were treated with oral sucralfate (5 mg/kg per day); those in group 2 underwent oral gentamycin therapy (5 mg/kg per day) for 5 days. Group 3 rats were treated with sucralfate and gentamycin for 5 days subsequent to the operation. The rats in group 4 served as controls, and received only 0.9% saline solution. Group 5 was a sham group. After 5 days of surgery, all rats were killed; the mesenteric lymph nodes (MLN), liver, and a segment of terminal ileum were harvested aseptically. The collected tissues were cultured in McCaunkey medium and chocolate agar. For each specimen, the colony-forming units (CFU) were calculated and the percentage of viable translocated micro-organisms was counted. In all rats who had ligation of the CBD, high numbers of bacteria were demonstrated in the liver, MLN, and ileum. In the liver of rats with sucralfate and/or gentamycin treatment, there was a marked reduction in CFU compared to the control group. Similarly, in the MLN measurements of CFU were higher in the control rats than the study groups. In both McCaunkey and chocolate media, the numbers of bacteria in control rats were significantly higher than in the study groups (P < 0.001). However, among the study groups themselves there was no significant difference in CFU in any of the specimens or culture media (P > 0.05). Experimentally-induced mechanical jaundice from ligation of the CBD causes significant BT in rats. Sucralfate and/or gentamycin may reduce the degree of BT from the bowel mucosa. We did not find any difference in protection from BT between sucralfate and gentamycin or both in rats with experimentally-induced mechanical jaundice. Accepted: 12 July 1999     

Implications of antenatal diagnosis of small-intestinal atresia in the 1990s

To assess the prevalence of antenatal diagnosis of small-intestinal atresias (SIA) in the modern era and determine its effect on management and outcome, the records of neonates admitted to a single institution in 1991–1996 with a diagnosis of SIA were reviewed. Duodenal atresia, atresias complicating meconium ileus, and those associated with gastroschisis were excluded. Of 14 neonates with SIA, 10 had jejunal atresia (JA) (Grosfeld type I, n = 1; type II, n = 2; type IIIa, n = 3; type IIIb [apple peel], n = 3; type IV, n = 1) and 4 had ileal atresia (IA) (type II, n = 1; type IIIa, n = 3). Antenatal diagnosis was made in 4 neonates (overall rate = 28%), including all 3 type IIIb JA, and 1 type II JA. None of the IAs were diagnosed antenatally. There were 2 deaths, both in patients with high JAs with less than 10 cm viable bowel. Only 1 of these was antenatally diagnosed. The median (range) times to full enteral feeding were 20 days (17–22) for antenatally-diagnosed JA, 14 days (11–26) for other JAs, and 8 days (6–15) for IAs. Antenatal diagnosis of SIA thus remains relatively infrequent (less than one-third of cases). When an antenatal diagnosis is made, the atresia is more likely to be proximal in location, requiring intensive and prolonged postnatal treatment. Provided a reasonable length of bowel remains, the outcome of SIA, whether antenatally diagnosed or not, is favorable. Accepted: 4 December 1998     

The effects of intravenous epidermal growth factor on bacterial translocation and central venous catheter infection in the rat total parenteral nutrition model

 Sepsis is a major complication of total parenteral nutrition (TPN) in children. Gut mucosal atrophy (GMA) and bacterial translocation (BT) occur in patients receiving TPN, and the translocated enteric organisms may cause central venous catheter (CVC) infection. Epidermal growth factor (EGF) has a trophic effect on the gut mucosa and may reduce BT, thereby reducing catheter infection. Using a rat TPN model, the relationship between GMA, BT, and catheter sepsis was examined and the effect on these of intravenous EGF was studied. There were four experimental groups. Group 1 had no CVC, Groups 2, 3, and 4 had a continuous central venous infusion as follows: group 2, saline; group 3, TPN; group 4, TPN with EGF. Groups 1 and 2 had free access to chow, groups 3 and 4 had no enteral feeds. After killing at 1 week, blood, tissue, and catheter specimens were cultured and mucosal morphology analysed. BT was defined as the presence of the same organism in cultures from the gut lumen and mesenteric lymph nodes (MLN). TPN only (group 3) resulted in GMA and BT, and 5 of 12 animals with BT had the same gut bacteria in blood and/or catheter cultures. The addition of EGF to the TPN significantly reduced GMA, BT to the MLN, and blood and/or catheter infections (P =< 0.05). In animals carrying enterococci, there was a significant reduction in translocation of enterococci (group 3: 8/14; group 4: 0/11; P < 0.05) and catheter infection by enterococci was prevented (group 3: 3/14; group 4: 0/11). EGF thus reduced GMA, BT, and blood and/or catheter infection when given IV to rats receiving TPN. Enterococcal translocation and subsequent blood and/or catheter infection was completely prevented, suggesting a selective effect of EGF. Accepted: 13 December 1999     

Reappraisal of the role of the bilioenteric conduit in the pathogenesis of postoperative cholangitis

The incidence of postoperative cholangitis has changed very little despite progressive improvement in the treatment of biliary atresia. The role of the bilioenteric conduit in its pathogenesis is still uncertain. A retrospective study of 39 patients undergoing either a conventional Kasai operation (group 1, n = 20) or with placement of an antireflux valve (group 2, n = 10) or lengthening (group 3, n = 9) of the jejunal conduit from 40 to 60 cm was performed to compare the incidence of cholangitis. Postoperative cholangitis developed in 18 of the 39 patients (46%). The incidence was 10/20 (50%) in group 1, 5/10 (50%) in group 2, and 3/9 (33%) in group 3 (P = 0.679). An animal experiment was conducted concomitantly to compare quantitative bacterial cultures of the bilioenteric anastomosis and the liver before and 1 week after Roux-en-Y hepaticojejunostomy (HPJ) in piglets without (group A, 25 cm) and with (group B, 50 cm) lengthening of the jejunal conduit in a porcine model of extrahepatic biliary obstruction. The growth of bacteria in both the bilioenteric anastomosis and the liver was not affected by lengthening the jejunal conduit from 25 to 50 cm (P = 0.612 and 0.057, respectively), despite a geometric increase in bacterial concentrations in both groups after HPJ. It is concluded that neither bacterial growth in the liver nor cholangitis following bile-duct reconstruction was affected by valving or lengthening the bilioenteric conduit. Accepted: 6 June 1999     

Early repair of inguinal hernia in premature babies

Inguinal hernia (IH) is relatively common in premature newborn infants, and the timing of surgical correction is controversial. We studied 40 premature infants who developed an IH and who were initially treated in a neonatal intensive care unit. Birth weight (BW) ranged from 492 to 2,401 g; 21 infants had a BW less than 1,000 g. The weight of the infants at operation ranged from 1,000 to 4,400 g. Twenty-one patients underwent herniotomy within 2 weeks after the diagnosis (short waiting group), in which 1 case of incarceration occurred; 19 waited longer than 2 weeks between diagnosis and surgery (long waiting group). Two cases of strangulation occurred in this latter group, and in 1 of those testicular necrosis occurred. Operation time was analysed in boys with bilateral herniotomy (n = 25): the short waiting group (n = 12) showed a significantly reduced operation time compared to the long waiting group (n = 13). Patients weighing less than 1,000 g at birth (n = 21) had a longer average waiting period for surgery. In the group of male patients with bilateral herniotomy, average operation time was longer in the group weighing less than 1,000 g at birth (n = 13) than in the group over 1,000 g (n = 12). Body weight at surgery did not affect operation time. It is concluded that early hernia repair should be considered in premature infants to avoid operative difficulties and gonadal ischaemia caused by incarceration. Accepted: 3 July 1997     

Prevalence of overweight and obesity in children aged 6–13 years—alarming increase in obesity in Cracow,Poland

This study in children aged 6–13 years (n = 1,499) was performed between October 2008 and March 2009. Height and weight measurements were taken to calculate BMI. The prevalence of overweight and obesity was determined by means of IOTF cut-offs with respect to age. Alarming is the fact that the percentage of obese children in Cracow increased dramatically from 1.04% in boys and 0.20% in girls in 1971 to 7% in boys and 3.6% in girls in 2009. In this report, a higher percentage of overweight boys was observed in rural boys (28.14%) than in urban ones (27.31%). Obesity was identified in an almost twice as high percentage of urban boys (7.78%) as in rural ones (3.52%). A higher percentage of overweight girls was registered in rural areas (16.49%) than in urban ones (16.09%). Obesity was prevailing in rural girls (4.12%) relative to their urban counterparts (3.44%). The highest number of overweight urban boys was diagnosed in the group of 12-year-olds (n = 48) and rural boys in the group of 10-year-olds (n = 39), as well as in urban girls aged 11 (n = 17) and rural girls aged 9 (n = 9). The highest number of obesity was observed in rural boys aged 12 (n = 3) and in urban boys aged 9 and 10 (n = 9 in both groups). In the group of girls, obesity prevailed in urban 9-year-olds (n = 5) and in rural 7-year-olds (n = 5). Conclusions: Overweight and obesity affect boys almost twice as frequently as girls. Obesity is twice as frequent in urban boys as in their rural peers.     

Characterization of irritable bowel syndrome and constipation in children with allergic diseases

Allergy is believed to play a role in the pathogenesis of irritable bowel syndrome (IBS) and constipation. We investigated whether allergic patients are more prone to constipation or IBS. In a multicenter study, two groups of outpatient children aged 3–13 years were included. In group 1, children with allergic symptoms were enrolled. Group 2 consisted of nonallergic children. In both groups, the assessment of IBS and constipation was carried out using a questionnaire based on the Rome criteria for functional gastrointestinal disorders. All children were examined and underwent skin prick tests (SPT) to foods and aeroallergens. The allergic group (n = 196) and controls (n = 127) were comparable with respect to sex, age, and anthropometric parameters. IBS was found in 6.6% of the allergic children and in 6.3% of the controls (p = 0.581). The frequency of constipation was similar in the two groups. In allergic children, positive SPTs to food and self-reported reactions to food were associated with IBS. Our results show that evaluation of constipation comorbidity is not required in allergic children. In allergic children with positive SPT to foods attention may be paid to IBS symptoms.     

The effect of phospholipase A2 on bacterial translocation in a cell culture model

 The activity of phospholipase (PL)A₂ is elevated in the intestinal epithelia of patients with inflammatory bowel disease (IBD). Recently, we reported that lysophosphatidylcholine (L-PC), the PLA₂ hydrolysis product of phosphatidylcholine (PC), stimulates bacterial translocation (BT) in an enterocyte cell-culture model. These two observations stimulated us to examine the effects of extracellular PLA₂ on intestinal epithelial permeability. Human Caco-2 enterocytes were grown to confluence on porous filters in the apical chamber of a two-chamber cell-culture system. Monolayer integrity and tight-junction permeability were measured by dextran blue (DB) permeability and transepithelial electric resistance (TEER). Monolayers were treated with PC, L-PC, or PLA₂ with and without PC. The magnitude of BT was determined 2 h after treatment by adding Escherichia coli to the apical chamber followed by quantitatively culturing basal chamber samples. Thin-layer chromatography (TLC) was utilized to verify PLA₂ hydrolysis of PC to L-PC. Statistical analysis was performed by one-way analysis of variance. The magnitude of BT across monolayers pretreated with PLA₂ + PC significantly increased compared to either PC or PLA₂ (6.83 ± 0.069, 2.41 ± 0.46, and 3.06 ± 1.14 log10 colony forming units/ml, respectively, P < 0.05). Absence of DB-permeability in any group confirmed monolayer integrity. TLC of PL samples harvested from the apical monolayer surface confirmed PC hydrolysis. PLA₂ mediates hydrolysis of PC to L-PC when both are applied to the apical surface of cultured enterocyte monolayers, resulting in increased BT and increased TEER with no damage to monolayer integrity. These observations may have implications in the pathogenesis and treatment strategies for IBD.     

Surfactant proteins and stable microbubbles in tracheal aspirates of infants with respiratory distress syndrome: relation to the degree of respiratory failure and response to exogenous surfactant

 Surfactant proteins (SP-A and SP-BC), albumin (ALB), and stable microbubble (SM) count were measured in tracheal aspirates from infants with respiratory distress syndrome (RDS) receiving single-dose Surfactant-TA (surfactant group, n = 32) or no surfactant (control group, n = 12), and those without RDS (non-RDS group, n = 8) to determine biochemical and biophysical status of surfactant in the course of RDS after surfactant replacement. Surfactant therapy resulted in immediate and sustained elevations of SP-BC/ALB and SM count with a rapid fall in ventilatory index to levels measured in the non-RDS group, whereas these indices improved slowly in the control group. The SP-A/ALB was initially low in both RDS groups and increased to levels measured in the non-RDS group by age 48 h. Multiple regression analysis showed that SP-BC/ALB, postnatal age, SM count, SM count/SP-A plus SP-BC, and surfactant therapy were independently associated with the severity of RDS as assessed by ventilatory index (r = 0.75, P < 0.0001; number of samples = 256). Infants with a relapse response to surfactant (n = 9) had levels of SP-A/ALB and SP-BC/ALB similar to those measured in the sustained group (n = 23), but had significantly lower SM count and SM count/SP-A plus SP-BC between 24 and 96 h of age. Conclusion Surfactant therapy normalizes the sur factant and respiratory status of infants with RDS. Surfactant dysfunction rather than depletion may explain the relapse response seen in some surfactant recipients. Received: 23 October 1995 / Accepted: 20 May 1996     

Natural killer cell cytotoxicity is deficient in newborns with sepsis and recurrent infections

 We investigated natural killer (NK) cell cytotoxicity in healthy preterm and full-term newborns in comparison to adults, to elucidate the possible role of delivery mode in influencing the NK activity and to evaluate the NK activity in severe neonatal pathological conditions such as bacterial sepsis and recurrent infections. NK cell cytotoxicity was investigated using a 4 h ⁵¹Cr release assay with K562 cells as targets expressed as percentage kill in the following study groups: full-term normal spontaneous vaginal delivery (n=55), full-term caesarean section (n=51), preterm normal spontaneous vaginal delivery (n=34), preterm caesarean section (n=28), bacterial sepsis (n=15), recurrent neonatal infections (n=8) and healthy adults aged between 22–42 years (n=89). NK activity for the normal newborns was determined in paired cord and 2–4 day-old neonate blood. The NK cell cytotoxicity in healthy newborns was significantly lower than in adults (P < 0.01). Prematurity was associated with a significant decrease in NK cell activity compared to full-term neonates (P < 0.05). The mode of delivery did not influence the NK cytotoxicity. In sepsis and recurrent infections, a dramatic decrease in NK cell cytotoxicity was seen related to healthy newborns (P < 0.01). Conclusion Natural killer cell cytotoxicity is deficient in both neonatal sepsis and recurrent infections. Received: 30 August 2000 and in revised form: 9 January 2001 / Accepted: 22 March 2001     

Gastric volvulus in children: the twists and turns of an unusual entity

Background Gastric volvulus in children is uncommon, and characteristic radiographic findings might not be recognized. Objective To present the spectrum of clinical and imaging findings, correlate the type of gastric volvulus with clinical outcome, and identify imaging findings to aid in early diagnosis. Materials and methods Medical records and imaging findings of ten children with gastric volvulus were reviewed. Imaging included abdominal radiographs, upper gastrointestinal (UGI) series, and CT. The diagnosis (organoaxial, mesenteroaxial or mixed type) was made on the UGI series (n = 9) and CT (n = 1), and confirmed surgically in seven children. Results Patients were classified based on presentation: four acute, four chronic, and two neonatal. All of the acute group (three mesenteroaxial and one mixed type) had abnormal radiographic findings: three spherical gastric distension, four paucity of distal gas, three elevated left hemidiaphragm, one overlapping pylorus and gastric fundus, one unusual nasogastric tube course, and one situs inversus. All underwent emergent surgery. Three had diaphragmatic abnormalities. One had heterotaxy. Patients in the chronic group (three organoaxial, one mesenteroaxial) had long-standing symptoms. Most had associated neurologic abnormalities. In the neonatal group, organoaxial volvulus was found incidentally on the UGI series. Conclusion A spectrum of findings in gastric volvulus exists. Mesenteroaxial volvulus has greater morbidity and mortality. Radiographic findings of spherical gastric dilatation, paucity of distal gas and diaphragmatic elevation are suggestive of acute volvulus, particularly in patients with predisposing factors.     

Spectrum of Gastritis in Celiac Disease in Childhood

Celiac disease (CD) may cause changes throughout the gastrointestinal tract. The pathology is best described in the distal duodenum and jejunum. It is also associated with lymphocytic gastritis (LG) and varioliform gastritis in adults and children, but the histologic spectrum in the gastric biopsy and the clinical implications are undefined. In this report we relate our experience with the clinical, endoscopic, and histologic changes in gastric biopsies in CD in childhood. Slides (hematoxylin and eosin stained) were reviewed from 33 celiac children, 5 having had more than 1 gastric biopsy during a 7-year period. Gastric intraepithelial lymphocyte (IEL) counts were compared with those of 10 histologically normal controls (normal range, 1–7 IEL/100 antral or body epithelial cells) and 10 nonceliac chronic gastritis (CG) biopsies without H. pylori (normal range, 1–19 IEL/100 antral cells), noting changes in the epithelium and lamina propria (LP). LG was present in 29/33 initial biopsy sets. Fifteen of 29 showed LG/CG. The IEL number was greater in LG/CG than in LG only (27.2 ± 9.3, n = 14 vs. 18.6 ± 13.4, n = 15 in the antrum; 23.5 ± 2.8, n = 4 vs. 13.0 ± 8.4 in the body). In CD the difference between these mean values and those of normal and nonceliac CG controls was statistically significant. In CG/LG the inflammatory infiltrate was predominantly diffuse/superficial in the LP; mucin depletion was noted in 11/15. The IELs were in the LG/CG range in two CG controls. The IELs were normal at follow-up in five cases. There were no statistically significant differences between the groups with respect to clinical parameters or gastric endoscopic findings. No child had varioliform gastritis. We conclude that in CD children, the stomach is endoscopically unremarkable but may show LG, or LG/CG with or without mucin depletion, or occasionally appear normal. Gastric histology returned to normal with gluten withdrawal. Normal gastric histology is not typical, but does not exclude CD. Received January 20, 1998; accepted January 14, 1999.     

A detailed analysis of changes in serum C-reactive protein levels in neonates treated for bacterial infection

A prospective study was undertaken to characterize the rate of increase, time of peak values and rates of decrease in serum concentrations of C-reactive protein (CRP) in a group of infants treated for neonatal bacterial infection. A total of 176 consecutively admitted neonates with birth weight >1500 g and without mechanical ventilation or central lines in situ, who received antibiotic therapy for suspected bacterial infection, were enrolled. The changes in serum CRP concentration in 60 of 63 infants who had CRP values above 20 mg/l 24–48 h after the beginning of treatment were analysed in detail. Initial increase rates in serum CRP levels of up to 4.5 mg/l per h were documented peak were reached at a mean of 19.5 h after antibiotic therapy had been initiated, but in some patients an increase in serum CRP levels occurred up to 40–48 h after the beginning of treatment. The mean serum half-life of CRP in infected neonates was 21 h (range 11.2–38 h). Conclusion In neonates with bacterial infection (defined by a combination of clinical signs and increased C-reactive protein and immature-total quotient values) no differences in the overall pattern nor in any of the particular phases of the C-reactive protein response curves could be observed between neonates with positive (n = 13) or negative blood cultures (n = 47). Received: 18 July 1997 / Accepted in revised form: 5 May 1998     

The complement component C4 in sudden infant death

The aim of the present study was to compare partial deletions of the complement C4 gene in victims of totally unexplained sudden infant death (SID) (n = 89) and borderline SID (n = 15) with and without slight infections prior to death, in cases of infectious death (n = 19), and in living infants with and without infections (n = 84). The SID and borderline SID groups were pooled. In this total SID group slight infections prior to death was associated with deletion of either the C4A or the C4B gene (P = 0.033), and the SID victims with such infections had a higher deletion frequency than the controls (P = 0.039). There were no differences between the living infants with and without upper airway infections. Conclusion The present study confirms that partial deletions of the C4 gene in combination with slight upper airway infections may be a risk factor in sudden infant death. Received: 8 June 1998 / Accepted in revised form: 7 September 1998     

Clustering of (auto)immune diseases with early-onset and complicated inflammatory bowel disease

Studies in adult inflammatory bowel disease (IBD) patients have highlighted associations with genetic and serologic markers and suggest an association with disease location, behaviour and natural history. Data on patients with Crohn’s disease (CD, n = 80), ulcerative colitis (UC, n = 15) and indeterminate colitis (n = 4) were collected. All individuals were analysed for CARD15 R702W, G908R and L1007fs for toll-like receptor 4 (TLR4) Asp299Gly and for anti-Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophil cytoplasmatic antibodies (pANCA). After a mean of 10.7 years of follow up, the disease behaviour changed in 45% of CD patients, in contrast to disease location, where only 12.5% had a change (p < 0.001). The younger the age at diagnosis, the more patients presented with colonic disease (p = 0.021). Also, more TLR4 Asp299 Gly variants were found when the age at onset was younger (p = 0.018). A large number of concomitant diseases were observed. There was no difference in the prevalence of TLR4 variants nor ASCA or pANCA between the patients with or without concomitant diseases. Patients who progressed more often needed surgery as compared to patients who remained free of stenosing or fistulising disease (27/32 or 84% versus 3/35 or 8.6%, respectively, p < 0.0001) and more often had concomitant immune-mediated diseases and a trend for more seroreactivity towards ASCA.