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A potential aetiologic agent was detected in the stools of 56% of 118 children hospitalized in Naples for acute diarrhoea. Rotavirus and Salmonella were the agents most commonly associated with disease, accounting for 23 and 17 percent of cases, respectively. Campylobacter jejuni, enterotoxigenic Escherichia coli, Yersinia and Shigella were less frequently isolated (total, 11% of cases). These findings fit well with the epidemiological picture described for other developed countries, except for the isolation rate of Salmonella which widely exceeds that reported in other investigations. Cytotoxic strains of E. coli and other Gram-negative bacilli were identified in the stools of 18 children; the possible pathogenic role of these strains is unknown and needs further investigation.

Infant mortality from acute diarrhoea has sharply declined in the last few decades throughout Europe. However, acute diarrhoea is still a very common occurrence in European children, who experience, in their first 3 years of life, approximately 1 episode/year. The commonest agent responsible for infectious diarrhoeas appears to be rotavirus, followed by campylobacter. Although water loss may be high, the mean sodium loss is close to 40 mmol/l of stool in rotaviral diarrhoea, and to 60 mmol/l in diarrhoeas due to invasive pathogens such as campylobacter and salmonella. Larger fluid losses but a somewhat lower sodium loss accompanies non-cholera secretory diarrhoeas, which appear to be commoner in infants than in older children. This evidence indicates that an ORS for European children should have a sodium concentration lower than 90 mmol/l which was primarily intended for use in developing countries. Clearly, the glucose concentration is crucial, as it is now evident that concentrations higher than the recommended 110 mmol/l may lead, particularly in rotaviral enteritis, to worsening of diarrhoea and development of hypernatraemia. Finally, it appears that in Europe the use of commercially available ORS is strikingly low, so that infants and children are often given a variety of "clear fluids", generally inadequate to ensure proper rehydration or maintenance of hydration. Thus an effort should be made not only to devise the "ideal" solution, but also to effectively implement its use.

The possible effects of conalbumin (a glycoprotein closely resembling lactoferrin) on iron transport across the brush border of intestinal cells of the rat were evaluated in vitro. Iron influx was measured in proximal and distal tracts of small intestine from either normal or iron-deprived rats, both in the presence of 1 or 10 mg/ml conalbumin and in its absence. Conalbumin did not affect iron uptake at any concentration and in any intestinal segment, either in normal or in iron-deprived animals. It was concluded that the luminal presence of conalbumin, even at a relatively high concentration, does not interfere with iron intestinal transport.

Some enteric strains of Escherichia coli release a heat-stable enterotoxin which, in contrast to cholera and heat-labile E. coli enterotoxins, stimulates guanylate cyclase (GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2). We have examined the tissue spcificity of its action and the relation of its action to those of the 8-bromo analogues of cyclic GMP and cyclic AMP. Heat-stable enterotoxin stimulated guanylate cyclase activity and increased cyclic GMP concentration throughout the small and large intestine. It increased transepithelial electric potential difference and short-circuit current in the jejunum, ileum and caecum but not in the duodenum or distal colon. This pattern of electrical responses was mimicked by 8-bromo-cyclic GMP. However, 8-bromo-cyclic AMP produced an electrical response in all intestinal segments. The enterotoxin failed to stimulate guanylate cyclase inliver, lung, pancreas or gastric antral mucosa. In the intestines, it stimulated only the particulate and not the soluble form of the enzyme. Preincubation of the toxin with intestinal membranes did not render it capable of stimulating pancreatic guanylate cyclase. Cytosol factors did not enhance the toxin's stimulation of intestinal guanylate cyclase. This study supports the role of cyclic GMP as intracellular mediator for heat-stable enterotoxin and suggests that the toxin affects a membrane-mediated mechanism for guanylate cyclase activation that is unique to the intestines.

Absorption of water from the intestine occurs in response to the osmotic gradient as a passive consequence of the active transfer of solutes (nutrients and electrolytes, with Na absorption playing a key role) from the intestinal lumen to the serosal side. During intestinal infections, several possible derangements of such a situation may occur, ultimately leading to the shift of net water absorption to secretion and, thus, to diarrhoea. In rotaviral diarrhoea, the mature enterocytes are invaded by the virus and exfoliate, thus inducing villous atrophy and crypt hyperplasia. Consequently, undigested and unabsorbed nutrients cause an osmolar diarrhoea, while the ongoing process of crypt secretion contributes by adding active anion and water secretion. In bacterial intestinal infections, the pathogenetic mechanisms are essentially mucosal invasion, adherence, cytotoxicity or release of enterotoxins. The pathophysiology of bacterial diarrhoea is best known for the latter mechanism; heat-labile and heat-stable families of enterotoxins have been described and characterised that act by inducing, respectively, an increase in the enterocyte's cyclic AMP or cyclic GMP content. Such alteration leads, in a morphologically intact mucosa, to changes in the major electrolyte transport processes that reverse net absorption of ions and water to net secretion and thus to secretory diarrhoea. As for nutrient absorption, although experimental evidence indicates an impairment of glucose and amino acid absorption in rotaviral diarrhoea, many clinical trials have shown the successful use of oral rehydration solutions in such circumstances. The same applies to bacterial-induced diarrhoeas; the well-established observation that, in enterotoxic diarrhoea of all kinds, the coupled transport of Na and nutrients such as glucose or amino acids is intact has proved to be the cornerstone of the highly successful, widespread use of oral rehydration solutions.

An ELISA technique using labelled antigen for the determination of cow's milk specific IgE in serum is described. The use of labelled antigen, rather than labelled antibody as in the RAST, permits avoidance of interference by antibodies other than IgE, such as IgG, at times responsible for a negative RAST. The results obtained with the 2 techniques in 43 infants with a positive cow's milk challenge showed a positive RAST in 28%, a positive ELISA in 35% and a positive RAST or ELISA in 42%. These findings suggest that the use of both ELISA and RAST permits in vitro diagnosis of cow's milk allergy in more patients than either test alone.

One hundred and eighteen consecutive cases of childhood acute diarrhoea (mean age: 10.5 months) were studied after admission to our Pediatric Unit in Naples over a 13-month period. A diagnosis was established in 92 patients (78%): 55% of patients were found to have an infectious enteritis (among them, 5 had ETEC infections and 1 had an ST-producing Klebsiella infection), 12% a parenteral infection, 11% cow's milk intolerance. The occurrence of gross blood (P less than 0.01), leukocytes, and reducing substances in the stools was more commonly associated with infectious enteritis than with diarrhoea due to all other causes. In 14 patients (8 of whom were malnourished), diarrhoea ran a prolonged course. In all, the eventual outcome was favourable. Our findings, while confirming that infectious enteritides account for most of acute diarrhoeas in children, stress the importance of parenteral infections and cow's milk intolerance in this condition. Also, the need for an accurate search for enterotoxigenicity of enterobacteria before ruling out their pathogenetic role is stressed.

An investigation was carried out on 61 children suffering from symptomatic giardiasis with the object of verifying the incidence and entity of lactose malabsorption. Furthermore, the possibility of a substitutive yogurt diet was verified in the lactose malabsorbers. The subjects, all children older than 1 year, were studied according to a schedule that included a lactose hydrogen breath test (BT) performed prior to therapy and a further BT 60 days following therapy. The subjects were divided in two groups: group A, 40 children, received a dose of 250 ml of cow's milk; group B, 21 children, received a stress dose of 2 g/kg lactose (max 50 g). Those subjects who were lactose malabsorbers at the 60 day follow-up were also given a BT at 75 days, and in the case of persistent malabsorption, a further BT was performed after 24 h with the administration of yogurt (450 g containing 12.1 g of lactose). Furthermore, 40 subjects matched for age and sex but without any GI complaints served as controls. The results showed lactose malabsorption to be frequent in children with Giardia lamblia symptomatic infection. According to the BT with a standard lactose load, all patients were malabsorbers; when testing lactose absorption with 250 ml of cow's milk, 45% of patients were found to be malabsorbers. In the latter subjects, the oral load of yogurt was uniformly well tolerated and gave rise to no H2 increment on the BT. We conclude that the occurrence of lactose malabsorption of nutritional relevance is common in children suffering or having suffered from giardiasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Escherichia coli heat-stable enterotoxins (ST) are classified into STa and STb according to their physicochemical and biologic characteristics. STa induces diarrhea, activating the guanylate cyclase-cGMP system. ST-like enterotoxins can be produced by bacteria other than E. coli, including Klebsiella pneumoniae. A Klebsiella ST has previously been shown to share some chemical and immunologic characteristics with E. coli ST. Aiming to define better the nature of Klebsiella ST, we have screened 237 children with diarrhea and 179 controls for ST-producing Klebsiella, using the SMA. We detected 26 Klebsiella strains from patients, two of which were positive in the SMA, and 36 from controls, all negative for ST. A partial purification was performed using an acetone precipitation followed by ultrafiltration and gel filtration techniques. Klebsiella toxin was heat-stable, methanol-soluble, sensitive to mercaptoethanol, active at acid pH values, but not at pH greater than 8. The time course of Klebsiella toxin in the SMA resembled that of E. coli STa. Klebsiella ST caused reduced Na absorption and net Cl secretion in rabbit ileal mucosa mounted in Ussing chambers. It was found to increase the cGMP but not the cAMP concentration. Finally, Klebsiella ST did not react with anti-E. coli STa MAb in a competitive ELISA. We conclude that K. pneumoniae may induce diarrhea through the production of an STa similar but not identical to E. coli STa.

Influxes of glycyl-L-proline (a dipeptide which is not hydrolysed in the membrane and is transported intact across the brush border) and of glycyl-L phenylalanine (a dipeptide which has affinity for the peptide transport system and is hydrolysed at the brush border membrane) have been studied in the small intestine of fetal, newborn and suckling rabbits. For glycyl-L-phenylalanine, transport as the intact dipeptide and 'membrane hydrolysis + amino acid transport' have been measured separately by using glycyl-L-proline and L-leucine as selective inhibitors of each pathway. For comparison, uptake of free glycine and of free phenylalanine has also been studied. The intestine of newborn rabbits is shown to have a translocation process for intact dipeptides which is saturable with a low Kt and stimulated by sodium ions, and which is not shared by free amino acids. This process resembles that described in adult animals, except that the maximal velocity is much higher in newborns. The developmental pattern of this uptake process for dipeptides differs markedly from that of free glycine, thus providing a new type of evidence for the distinction between amino acid and dipeptide transport processes. The developmental pattern of the free phenylalanine uptake process also differs from the development of the 'superficial hydrolysis + amino acid transport' component of glycl-L-phenylalanine uptake. These data suggest that the advantage of mucosal uptake of peptides, compared to the uptake of free amino acids, is much greater in the early stages of postnatal life than in the adult.