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Senna laxatives are used worldwide. However, their misuse can lead to chronic mucosal inflammation with the accumulation of pigment-laden leukocytes and may cause colon cells to undergo apoptosis. This study explores the mechanisms by which rhein, an active component of senna, acts on a human intestinal cell line to induce ion secretion, apoptosis, and indirect chemotaxis of polymorphonuclear leukocytes.Human colonic adenocarcinoma (CaCo-2) monolayer cells, in the presence or in the absence of rhein, were used to monitor the production of reactive nitrogen species using the Griess reaction. Modified Ussing chambers were used to study electrolyte secretion. The capacity to recruit human polymorphonuclear leukocytes was evaluated using masked well chemotaxis chambers. Rhein-induced apoptosis was investigated by counting apoptotic nuclei stained with Hoechst 33258 dye.Rhein caused a dose-dependent increase in short-circuit current that was abolished in chloride-free bathing buffer or by preincubating with 100 micromol/L NG-nitro-L-arginine (L-NAME) methyl ester. The concentration that maximally stimulated intestinal secretion, 50 micromol/L rhein, induced nitrate production. Supernatants obtained from CaCo-2 cultures after incubation with 50 micromol/L rhein stimulated a time-dependent polymorphonuclear leukocytes chemotaxis that was significantly decreased with 100 micromol/L L-NAME, whereas rhein per se was not active. Neutralizing antibodies anti-interleukin-8 (IL-8) and anti-ENA78 also inhibited chemotaxis. Overnight rhein incubation produced an increased number of apoptotic cells in the culture supernatant that was significantly decreased by preincubation with 100 micromol/L L-NAME. Light-degraded rhein had no effects on CaCo-2 monolayers.The integrity of rhein is crucial to generating nitric oxide, which mediates, with different time courses, ion secretion, chemotaxis, and apoptosis of human-derived cells.

Gestational maturation of gastrointestinalmotility is a key factor in readiness of the pretermneonates for enteral nutrition. Since gastric motilitymainly depends on the electrical activity of the smooth muscle cells, it was of interest to investigatethe developmental aspects of electrical activity of thestomach. The latter was recorded weekly throughcutaneous electrogastrography in 27 preterm infants (aged 29-34 weeks of gestation). Recordingswere done for 1 hr before and 1 hr after meal. Theelectrogastrographic variables measured were: percentageof normal gastric rhythm, i.e., 2-4 cpm; percentage of tachygastria (>4 cpm); the fed-to-fastingratio of the dominant electrogastrographic power; andthe instability coefficient of the dominant frequency.Data were compared with those measured in 10 full-term infants. Peaks of normal electricalactivity (2-4 cpm) were present in most of therecordings at all the gestational ages; however,percentages of both normal electrical rhythm andtachygastria in preterm infants were similar to thosemeasured in full-term infants (mean ± SD) (normalrhythm; fasting: 70.2 ± 3.8, fed: 72.2 ±5.0; tachygastria: fasting: 24.6 ± 4.0, fed: 19.1± 3.5) by 35 weeks of gestation (normal rhythm; fasting:67.5 ± 2.0, fed: 69.6 ± 4.4; tachygastria:fasting: 27.1 ± 4.0, fed: 25.6 ± 4.1). Thecoefficient of instability of the dominant frequency inpreterm infants was also similar to the value measuredin full-term infants by 35 weeks of gestation, whereasthe EGG power showed a significant increase in thepostprandial state at all the gestational ages. We conclude that a maturation pattern of theelectrical activity of the stomach can be detected bymeans of a noninvasive tool such as cutaneouselectrogastrography: a normal electrical rhythm can bedetected at very early gestational ages; however, thisactivity becomes dominant at around the 35 weeks ofgestational age. In preterm infants developmentalchanges of gastric electrical activity are a function of advancing postnatal age.

D-myo-Inositol 1,4,5-triphosphate (IP 3 ) is a key second messenger in many cells, including macrophages, T and B cells, and neutrophils, in which it regulates free intracellular calcium ion levels. In human polymorphonuclear leukocytes the rise of intracellular [Ca 2+ ] is the signal that activates a number of functions such as adherence, aggregation, chemotaxis, and degranulation, which are typically depressed in newborn infants. IP 3 generation can be stimulated by N-formyl-methionyl-leucyl-phenylalanine (fMLP) tripeptide, which mimics the naturally occurring bacterial oligopeptides. In this study both neonatal and adult polymorphonuclear leukocytes were stimulated by fMLP (1 X 10 -6 M) and the levels of IP 3 were assayed by a specific radiometric method. The time course of IP 3 generation was studied for up to 60 s in a total of 10 samples. The response appeared reduced in cord blood samples. To confirm this observation, we extended our study to a larger number of samples, quantitating [IP 3 ] at the time peak of 10 s. As expected IP 3 generation was significantly (F test, p < 0.0001, n = 39) lower in newborns than in adults (means ± SD = 0.64 ± 0.25 ; 1.26 ± 0.36, ng/10 6 cells, respectively). Besides soluble stimulus, neutrophils were treated with a particulate stimulus, namely serum-treated zymosan, which is also able to stimulate IP 3 synthesis from polymorphonuclear leukocytes. Serum-treated zymosan produced a prolonged elevation in the level of IP 3 , reaching a plateau within 120 s in both cord blood and in control samples. At the 120-s time point significantly (F test, p < 0.002, n = 10) lower amounts of IP 3 were found in newborn samples than in adult preparations (mean ± SD = 1.09 ± 0.45 ; 2.54 ± 0.55, ng/10 6 cells, respectively). These data suggest that an impaired synthesis of IP 3 is involved in the defective signal transduction of neonatal polymorphonuclear leukocytes and could represent an important biochemical mechanism behind the defective functions of neonatal neutrophils.

In 10 children with cystic fibrosis and persisting steatorrhoea, supplementation with taurine (30-40 mg/kg/day) was given for two months as an adjunct to the usual pancreatic enzyme treatment. A three day fat and energy balance was performed in patients with cystic fibrosis, before and after the supplementation, and in seven healthy controls who did not receive taurine. Faecal fat was measured by a gravimetric method and stool energy was determined using a bomb calorimeter. Patients with cystic fibrosis, before and after taurine, and healthy controls received the same fat and energy intake (calculated by a dietitian). In patients with cystic fibrosis taurine did not produce any improvement of steatorrhoea (mean (SD) faecal fat 8.7 (3.3) v 11.2 (7.0) g/day, respectively before and after the supplementation), of faecal energy loss (0.978 (0.468) v 1.133 (0.539) MJ/day), of faecal fat expressed as percent of fat intake (13.4 (5.6) v 15.1 (9.8)%), and of faecal energy expressed as percent of energy intake (9.9 (3.6) v 11.2 (5.7)%). Healthy controls had significant lower fat (3.5 (2.3) g/day) and energy 0.576 (0.355) MJ/day faecal losses. In conclusion, taurine failed to decrease significantly fat and energy losses. Our study does not support the use of taurine supplementation in the nutritional management of cystic fibrosis.

Major questions are whether mothers infected with the Human Immunodeficiency Virus type 1 (HIV-1) transmit the virus through breast milk and the magnitude of the additional transmission risk. The demonstration of a dose-response effect is an epidemiological method to demonstrate causality. Thus, a study was carried out by the Italian Register for HIV Infection in Children on 961 children of known infection status. Duration of breast-feeding was considered as the level of exposure in 168 ever breast-fed children. Results showed that duration of practice significantly increased the risk of transmission. The adjusted infection odds ratio for one day of breast- versus exclusive formula-feeding was 1.19 with narrow confidence limits (1.10-1.28). In a second study by the Register on 556 children of known infection status and derived prospectively, an infection odds ratio of 2.55 (confidence interval: 1.03-6.37) was calculated in breast- versus exclusively formula-fed children. Several lines of evidence, including the above-mentioned data from the Italian Register for HIV Infection in Children, showed a contribution of breast-feeding to mother-to-child HIV-1 transmission. Thus, this practice is now discouraged in HIV-1 infected mothers living in industrialized societies where formula feeding is practical and attainable. Mode of feeding was known in 2183 children enrolled in the Register and born to HIV-1 infected mothers since 1981. It could be observed that feeding habits of at-risk infants changed in Italy in the middle 1980s, when a large majority of subjects was identified at birth.(ABSTRACT TRUNCATED AT 250 WORDS)

Children infected with HIV do not necessarily develop AIDS to a set pattern but can be divided into long-term and short-term survivors. We examined long-term survival in children perinatally infected with HIV-1. Out of a total of 624, we studied 182 children who survived longer than 5 years (long-term survivors [LTS]) and 120 children who died of HIV-1-related disease before 5 years (defined as short-term survivors [STS]). 28 (15%) LTS were symptomless (Centers for Disease Control [CDC] P-1 children). 154 (85%) had symptoms (CDC P-2). The proportion of LTS with less than 0.2 x 10(9)/CD4 cells per L was 24/116 (21%) at 61-72 months, rising to 11/26 (41%) at more than 96 months. On at least one occasion, p24 antigenaemia was observed in 112 (62%) LTS. Annual rate of CD4 cell loss was lower in LTS (25% [95% CI: 21-29]) than in STS (53% [45-60]) and in LTS symptomless or with solitary P-2A signs (17%; [13-21]) than in LTS with severe manifestations (30% [25-35]). A new outlook emerges. A substantial number of children do survive after early childhood; severe diseases; low CD4 cell numbers, and p24 antigenaemia do not necessarily preclude long-term survival. The study shows that a CD4 cell decrease early in life can be predictive of outcome.

The aim of this comparative study was to investigate the clinical usefulness of the measurement of Toxoplasma gondii IgG avidity in the postnatal diagnosis of congenital toxoplasmosis. IgG avidity values in serum samples from infants with congenital infection were compared with those in samples from uninfected infants, all born to mothers with toxoplasmosis acquired during gestation. This analysis revealed that IgG avidity values soon after birth reflected maternal values in the large majority of the samples. Low or borderline IgG avidity values were systematically found in the cohort of congenitally infected subjects. After birth, IgG avidity values slowly increased over time for up to 2 years in congenitally infected subjects. On the contrary, IgG avidity values in the uninfected infants remained stable over time. The presence of low IgG avidity in a newborn can be considered a marker of maternal seroconversion in the second or third trimester of gestation and, as a consequence, an indicator of risk for congenital toxoplasmosis. An IgG avidity assay can be easily carried out with antibodies eluted from dried blood spots (Guthrie cards), providing an opportunity to retrospectively evaluate the risk of congenital infection in special clinical circumstances, for example when suspicion of congenital infection arises during late infancy.

The aim of the study was the evaluation of the relationship between chemical fat analysis and some more rapid tests proposed to estimate steatorrhoea. Stool collections (72 h) were obtained on 32 occasions in 22 patients with cystic fibrosis and in seven healthy children. A very close relationship was found between faecal fat, as measured by standard chemical methods, and faecal energy (r = 0.95, P0.001). We conclude that the determination of faecal energy, easier to measure than faecal fat, can provide reliable information about the extent of steatorrhoea in cystic fibrosis.

Modulation of neutrophil response to naturally occurring stimuli is important to avoid host tissue injure. Both soluble and particulate stimuli may induce superoxide anion generation in human polymorphonuclear leukocytes. Recently wortannin has been shown to inhibit the N-formyl-methionyl-leucyl-phenylalanine (fMLP) induced activation of respiratory burst via phosphatidylinositol 3-kinase. However no data are available about the effect of the inhibitor on the respiratory burst induced by a particulate stimulus. In this paper we studied the effect of wortmannin on E. coli induced respiratory burst and phagocytosis by flow cytometry, which allows the quantitation of both H2O2 production and ingested bacteria in whole blood samples without the need of purification and concomitant manipulation of the cells. The effects of worthmannin on fMLP-induced chemotaxis was also examined by the under agarose method. Neither the E. coli nor the fMLP-induced responses were blocked by wortmannin, suggesting that PI 3-kinase activity is not required to activate these neutrophil functions. Since it is known that the respiratory burst elicited by fMLP is blocked by wortmannin, our results suggest that the generation of oxygen radicals is controlled via different signal transduction pathways, depending on the agonist used.

Intestinal lymphangiectasia is characterized by obstruction of lymph drainage from the small intestine and lacteal dilation that distorts the villus architecture. Lymphatic vessel obstruction and elevated intestinal lymphatic pressure in turn cause lymphatic leakage into the intestinal lumen, thus resulting in malabsorption and protein-losing enteropathy. Intestinal lymphangiectasia can be congenital or secondary to a disease that blocks intestinal lymph drainage. We describe the first case of intestinal lymphangiectasia in a premature infant. The infant presented with peripheral edema and low serum albumin; high fecal concentration of α1-antitrypsin documented intestinal protein loss. Endoscopy showed white opaque spots on the duodenal mucosa, which indicates dilated lacteal vessels. Histology confirmed dilated lacteals and also showed villus blunting. A formula containing a high concentration of medium chain triglycerides resulted in a rapid clinical improvement and normalization of biochemical variables. These features should alert neonatologists to the possibility of intestinal lymphangiectasia in newborns with hypoalbuminemia and peripheral edema. The intestinal tract should be examined for enteric protein losses if other causes (ie, malnutrition and protein loss from other sites) are excluded. The diagnosis rests on jejunal biopsy demonstrating dilated lymphatic lacteal vessels.

Fifty-one children with total or partial IgA deficiency were compared for clinical and laboratory features. Serum IgG were higher in total IgA deficiency. Moreover, while no subject with partial IgA deficiency showed autoantibodies, 48% of the group with total IgA deficiency showed one or more autoantibodies. These data support the notion that total and partial deficiencies are two distinct entities.

The functional immaturity of lung in preterm babies leads to an acute progressive breathing failure, the so-called hyaline membrane disease (HMD). In the last few years, neonatal mortality for HMD, approximately 1.5%, has greatly decreased with skilled nursing and physician management, but it still represents a major cause of mortality [1]. An important point is its prevention, inducing fetal lung maturation in utero by means of drugs administered to the mother [2] and developing surfactant substitutes for the treatment of surfactant deficiency at birth or following the development of HMD [3,4]. As preterm newborn infants of gestational age

Seventeen paediatric patients with immunodeficiency syndromes (10 with selective IgA deficiency, four with panhypogammaglobulinaemia, and three with selective T cell deficiency) were investigated for bacterial overgrowth of the small intestine and gut permeability to macromolecules. Five of 12 patients showed viable bacterial counts of more than 2 x 10(5)/ml in jejunal fluid. Bacterial overgrowth was also confirmed indirectly by breath hydrogen determination, which was higher than 10 ppm in four of the five patients with positive jejunal culture. Gut permeability to lactulose and L-rhamnose was abnormal in 16 of the 17 immunodeficient patients, who also had higher mean urinary excretion ratios than control subjects-mean (SD) values were 0.216 (0.160) and 0.029 (0.002), respectively. These studies indicate that bacterial overgrowth of the small intestine is a common feature in immunodeficient patients, regardless of the immunological abnormality. Moreover, these patients have an increased gut permeability to macromolecules.

DiGeorge anomaly (DGA) represents a heterogeneous entity, which is often sporadic, although familial cases and the association with monosomy 22q11 have been reported. Recently, a few patients with 10p deletion syndrome and immunological and other laboratory findings similar to DGA have been described. We report on an additional case of partial DGA associated with 10p deletion.

Four patients with common, variable agammaglobulinemia were preveiously reported to have normal numbers of circulating B lymphocytes which synthesized normal amounts of IgG in tissue culture but failed to secrete the newly synthesized IgG. The B lymphocytes of these patients fail to incorporate [3H]mannose and/or [3H]glucosamine into newly synthesized IgG, whereas such incorporation appears to occur just before IgG secretion in cultures of normal B lymphocytes.

Extract: The enzymatic activity hydrolyzing γ-glutamyl-β-naphthylamide (γ-glutamyltranspeptidase, GGTP) was studied in the small intestine of human adults and fetuses. Surgical biopsies taken from the proximal jejunum approximately 10 cm from the ligament of Treitz served as the source of the enzyme for adult subjects. The entire small bowel was obtained from fetuses of different ages and divided into three thirds for enzymatic assay. All samples were frozen immediately and used within 1–4 months. It was shown that enzymatic activities stored at −20° are stable for that period.

Mean birth weights and percentile charts are given for 161 singleton infants born between 24 and 30 weeks' gestation at the 2nd School of Medicine of Naples. This chart is the first for a Mediterranean population. Our data are similar to those reported from a United Kingdom population and from Japan, suggesting that ethnic differences in birth weight at this gestational age are unimportant.

The perinatal histories of 27 newborn infants with NEC were compared to those of 54 infants of equivalent birth weight who did not have NEC during an 8-year study period to see if possible predisposing factors were independent of the confounding effect of birth weight. No differences were observed in gestational age, degree of intrauterine growth retardation, premature rupture of membranes, perinatal asphyxia, skin temperature at admission, haematocrit, presence or absence of respiratory distress syndrome, umbilical catheter placement, start and type of feeding or presence of positive blood cultures. Prematurity is the greatest risk factor predisposing to the development of NEC and the perinatal problems which precede the onset of NEC are common among all premature infants.

A sensitive radioimmunoassay for IgG gliadin antibodies is described. Serum specimens were added to wells of plastic microtitre plates coated with gliadin. After removal of the unbound material, gliadin antibodies were detected by adding 125I-labelled staphylococcal protein A (125I-SpA). Serum specimens from coeliac patients on a normal diet or on a gluten-free diet were tested, as well as sera from an age-matched control group. Measurements to obtain precise quantitative values were made with gliadin antibody-rich serum as reference standard. High titres of gliadin antibodies were found in 18 out of 19 coeliac patients on a normal diet (95%); in patients on a strict gluten-free diet serum values did not exceed 2 S.D. of the control mean. Due to the high senstivity of the method a low but detectable amount of gliadin antibody was present in the sera of all controls.

Publisher Summary This chapter discusses the localization of the IgG effector site for monocyte receptors based on a study. It reviews a study in which papain digestion of human IgG followed by cleavage with CNBr of the isolated Fc fragments yielded dialyzable peptides estimated to consist of 4–7% of the original amount of IgG. Three different preparations of peptides at a concentration of 2.5 mg/ml inhibited rosette formation of antibody coated ORh+ erythrocytes with human monocytes to the extent of 64%, 70%, and 78%. After separation of the peptides into seven fractions by descending paper chromatography, the inhibiting activity was present only in two fractions showing mobility in the RF ranges of 0. 35–0.50 and 0.50–0. 70, respectively. Both fractions were labeled with iodinated 3-(4-hydroxy) phenylpropionic acid N-hydroxysuccinimide ester and allowed to absorb on monocyte monolayers. Adherent radiolabeled peptides were eluted by incubation with IgG and subsequently purified by chromatography on paper and silicic acid. A single radioactive spot with an RF of 0.8, coinciding with the presence of a peptide, was eluted from the silicic acid chromatograms of both fractions. Samples were analyzed for amino acid composition and tested for rosette inhibition. Amino acid analysis revealed 10 amino acid residues on the following composition: Tyr, Ser2, Lys2, Leu, Thr, Val, Asp, and Arg.A concentration of O.6 nmol of peptide per monolayer of 8 × 105 monocytes inhibited 88–90% rosette formation. On the basis of observation that a sequence of this composition comprises residues 407–416 of the Eu myeloma gamma chain, the effector site of IgG for monocyte binding was thus localized in the CH3 region of the gamma chain.

This study was performed in order to evaluate possible changes in behavior in jaundiced infants without perinatal complications other than hyperbilirubinemia treated with phototherapy. Thirty jaundiced infants (mean bilirubinemia 13.3 mg/100 ml, range 8.4-17.5) born spontaneously at term and undergoing phototherapy for 6 h or more, and 30 comparison subjects similar for sex, birthweight, gestational age, Apgar score, obstetrical history and father's profession were examined during the 3rd day of life according to Brazelton Neonatal Behavior Assessment Scale (BNBAS). For 6 of 26 items we found higher values for comparison group (Wilcoxon's Test): inanimate visual median (m.) 5 vs. 3 (P less than 0.05); animate visual m. 5 vs. 3.5 (P less than 0.01); visual and auditory 5.5 vs. 4 (P less than 0.005); pull-to-sit m. 6 vs. 5 (P less than 0.01); cuddliness m. 5 vs. 4 (P less than 0.01); alertness m. 5 vs. 4 (P less than 0.005). Visual orientation responses were the most compromised. On the 4th day of life, 14 infants who had terminated phototherapy at least 2 h before (mean 9.9 h) were compared with their matched comparison group subjects and the same significantly poorer performances, mainly in visual orientation, were found. At one month of age, 12 of these infants treated with phototherapy still showed a significantly poorer performance in 2 items of orientation: inanimate visual m. 6 vs. 4.5 (P less than 0.05); visual and auditory m. 6.5 vs. 4 (P less than 0.05). Whether these results depend on the jaundice or on the phototherapy remain to be established.

This paper reports on a preterm infant with meconium peritonitis in which prenatal sonography demonstrated calcified peritoneal meconium associated with fetal ascites. His spontaneous and favorable outcome is described and other causes of neonatal abdominal calcifications are discussed.

This study was performed to determine whether covering the eyes with an opaque screen over the head end of the bassinet instead of the normal patch would improve the behavioral organization of jaundiced, but otherwise healthy, term infants treated with phototherapy. 38 matched infants were randomly assigned to have a patch or a screen. Serum biliru-bin at the time of observation was 11.2–17.5 mg/l00 ml (x = 13.7, patch) and 9.4–16.4 mg/100 ml (x = 13.4, screen). 19 infants, of whom 11 were jaundiced (6.2–14.3 mg/l00 ml, x = 10.3), served as control subjects. The infants were examined with the Brazelton scale on the 3rd day after birth, when the patch subjects had been under blue light from 6 to 45 h (x = 23.9), and the screen subjects from 6 to 61.5 h (x = 22.6). The control subjects scored better (all differences, p < 0.05) than the patch subjects on inanimate visual, animate visual, visual and auditory, alertness. The control subjects also did better than the screen subjects on inanimate visual, animate visual, animate auditory, visual and auditory, alertness, but poorer on motor maturity and consolability. The screen subjects did poorer than the patch subjects only on skin color lability. At 1 month of age, 9 sets of matched infants were examined. The only difference was that the control subjects did better than the patch subjects on animate visual and lability of state. Our data confirm the poorer short-term orientation performance of jaundiced infants treated with phototherapy but do not indicate that covering the eyes with an opaque screen improves behavioral organization.

Thirty jaundiced neonates with diarrhoea who were being treated with phototherapy and 30 matched control infants were studied to try and find out the cause of the diarrhoea. Faecal osmolality and electrolyte concentrations were measured, which gave clear evidence that the diarrhoea arose from intestinal secretion. Rectal water and electrolyte absorption in 10 jaundiced infants receiving phototherapy, in 10 jaundiced infants not receiving phototherapy, and in 10 healthy controls was measured with a rectal dialysis bag. A further group of eight jaundiced infants was also studied both during and after phototherapy to document the reversal of ion transport changes. Absorption of water, sodium chloride, and potassium was significantly impaired in the patients receiving phototherapy compared with each of the control groups. Such impairment was transient, as it was not apparent when the jaundice faded and phototherapy was stopped. These data show that the colon plays a part in the pathogenesis of secretory diarrhoea and that both hyperbilirubinaemia and phototherapy are necessary for such an effect to develop.

A peptide consisting of 10 amino acids derived from the CH3 region of human IgG was shown to bind to monocytes and to inhibit rosette formation of antibody-coated erythrocytes with human monocytes. Two myeloma proteins of the IgG1 and IgG3 subclass, both with known deletions in the CH2 region of the gamma chain, showed unimpaired ability to bind to monocytes. These experiments suggest that the isolated peptide represents the primary site of attachment of IgG to monocytes.

The digestibility of various starches has been studied in normal infants of different ages. During balance periods of 3 days, while the infants were receiving known dietary quantities of the starch to be tested, the fecal content of lactic acid, glucose, dextrins, and starch was measured. After the first year of life, children were able to absorb almost completely 170 gm/m 2 of body surface of cooked wheat starch given in the form of biscuit or macaroni. A lower absorption coefficient was found for potato starch given in the form of biscuit. Cooked wheat, tapioca, corn, rice, and potato starch in amounts of 45 and 85 gm/m 2 /day, respectively, for 1- and 3-moold infants, were almost completely absorbed. In 1-mo-old infants larger amounts (110 gm/m 2 /day) of cooked rice starch were well tolerated; it should therefore be possible to provide a large part of the carbohydrate requirements of infants from the first month of life with cooked starches.