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Biomedical subjects

S Guandalini

Publications and source records attributed to S Guandalini.

At least 55 records · Page 3Linked to original sources
PubMed1991

Fat body mass and pharmacokinetics of oral 6-mercaptopurine in children with acute lymphoblastic leukemia.

To evaluate the reasons for the wide variability in bioavailability of orally administered 6-mercaptopurine in children with acute lymphoblastic leukemia, we studied several pharmacokinetic parameters of the drug in 18 affected children receiving remission maintenance therapy, and compared them with their anthropometric data and with the results of intestinal function tests. No correlation was found between estimates of small intestinal absorption (the oral lactose tolerance test and 1 h blood xylose test) and 6-mercaptopurine serum levels. Of the anthropometric measurements considered, only the weight/height percentile (an index of the fat body mass) strongly and linearly correlated with the area under the curve of 6-mercaptopurine. The dose of 75 mg of 6-mercaptopurine/m2 of body surface resulted in higher serum concentrations in children below the 75th percentile than in those with a weight/height ratio exceeding the 75th percentile. In conclusion, these data caution about the risk of underdosing 6-mercaptopurine in overweight children when administering it on the basis of body surface area.

Administration, Oral↗
PubMed1990

Bile acids reversible effects on small intestinal permeability. An in vitro study in the rabbit.

To define the action of deconjugated bile acids on the small intestinal permeability in an in vitro system, we investigated the effects of chenodeoxycholic acid and ursodeoxycholic acid on the rate of transmural flux of lactulose in jejunal and ileal mucosa of rabbits, stripped of their muscle layers and mounted in Ussing chambers. In a series of experiments, tissue samples from small intestinal segments either exposed to bile acids or not also were examined by scanning and transmission electron microscopy to study the integrity of the tight junctions. Results show that chenodeoxycholate, starting at the concentration of 0.1 mM, enhanced in a dose-related manner the transepithelial flux of lactulose in the ileum. Both chenodeoxycholate (0.5 mM) and ursodeoxycholate (0.5 mM) significantly increased mucosal permeability to lactulose in jejunum and ileum; the effect of chenodeoxycholate was also shown to be reversible, as it completely disappeared within 40 min after its withdrawal and it did not result in permanent changes of epithelial transport function. Finally, the tight junctions appeared loosened by the addition of 1 mM chenodeoxycholate, suggesting that this is the major site of the transient bile acid increase of small intestinal permeability to compounds such as lactulose, having a molecular radius wider than 0.5 nm.

Animals↗
PubMed1990

Intestinal giardiasis associated with ophthalmologic changes.

In an ophthalmologic study of 90 children with symptomatic giardiasis, ocular alterations were found in 10. Eight of these subjects presented an extensive "salt and pepper" degeneration of the pigmented epithelium involving 360 degrees of the midperiphery of both eyes. In one of the eight children, the pigmented epithelium showed atrophic areas, and in another there was a small hard exudate in the left eye. Of 2 remaining of the 10 children with ocular alterations, 1 presented with slight decoloration of the temporal half of the optic disc, and the other was affected by chorioretinitis. After single-dose antiprotozoic therapy (tinidazole 50 mg/kg), parasitologic tests were negative in all subjects and remained so throughout a 1-year follow-up. However, the characteristic epithelial lesion remained unaltered in all eight children for the entire follow-up period, as well as the optic disc decoloration in the only observed case. The child affected by chorioretinitis recovered after 3 weeks of combined treatment with bethametasone plus deflazacort. In two control groups, 1 of 200 healthy children and 1 of 200 children with gastrointestinal symptoms but without giardiasis, no case of "salt and pepper" degeneration of the pigmented epithelium or other significant ocular alterations was found.

Child↗
PubMed1990

Current controversies in oral rehydration solution formulation.

Although the importance of oral rehydration therapy for acute diarrhea is unquestioned, controversy remains about the preparation and formulation of the oral rehydration solutions (ORS). There is disagreement about whether the ORS should be homemade or commercially prepared, what constitutes the optimal sodium content, what base (if any) should be present in the ORS, and whether other nutrients can be substituted entirely or in part for glucose. These issues are discussed and recommendations for the ideal ORS are presented.

Fluid Therapy↗
PubMed1989

Cimetidine treatment of reflux esophagitis in children: an Italian multicentric study.

The effectiveness of cimetidine (30-40 mg/kg/day) was evaluated in 32 children with gastroesophageal reflux disease complicated by esophagitis who entered a random double-blind trial for 12 weeks. Esophagitis was diagnosed in all patients by endoscopy with biopsy. Seventeen patients (age, mean +/- SD: 21.7 +/- 37.65 months) received cimetidine (c-pts), and 15 (age, mean +/- SD: 29.03 +/- 39.73 months) received a placebo (p-pts). All patients received intensive postural therapy. Based on clinical and endoscopic (and histologic) data, 12 c-pts and three p-pts were healed (p less than 0.01), the condition of four c-pts and three p-pts had improved (not statistically significant), and the condition of one c-pt and nine p-pts had worsened (p less than 0.01). Both clinical and esophagitis scores significantly decreased only in the c-pt group, as compared with p-pts. Improvement of esophagitis was seen in all (100%) of c-pts with mild or moderate esophagitis versus 57.14% of p-pts (p less than 0.01) and in 87.5% of c-pts with severe esophagitis as compared with 25% of the p-pt group (p less than 0.01). We conclude that cimetidine is an effective agent for treatment of reflux esophagitis in children. Although gastroesophageal reflux disease in infancy has a naturally self-limited course with conservative care (thickened feedings and posture adjustment), extensive pharmacologic therapy is needed in the presence of esophagitis.

Adolescent↗
PubMed1989

Lactose malabsorption in children with symptomatic Giardia lamblia infection: feasibility of yogurt supplementation.

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)

Adolescent↗
PubMed1989

Overview of childhood acute diarrhoea in Europe: implications for oral rehydration therapy.

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.

Acute Disease↗
PubMed1989

Heat stable enterotoxin produced by Escherichia coli in acute diarrhoea.

We screened 569 children with acute onset diarrhoea from five Italian towns for heat stable enterotoxin produced by Escherichia coli. We compared an enzyme linked immunoabsorbent assay (ELISA) with the standard suckling mouse assay for detection of the enterotoxin. A total of 31 (5.4%) children were found who had strains of E coli that produced heat stable enterotoxin: 26 strains were positive in both tests, four only in the suckling mouse assay, and one only in the ELISA. Compared with the suckling mouse assay the sensitivity of the ELISA was 87% and the specificity was 99.8%. The mean age of the children with E coli that produced heat stable enterotoxin was 22 months. Fifteen (48%) of the children had ingested potentially contaminated food and five (17%) had a previous contact with someone with diarrhoea. The clinical picture was milder than that described in developing countries. Faecal osmolality and the osmolal gap were consistent with a secretory diarrhoea in 12 out of 15 (80%) of these children. The mean duration of the diarrhoea was five days. Heat stable enterotoxin produced by E coli is a common cause of mild diarrhoeal illness in Italian children.

Adolescent↗
PubMed1989

Diarrhoea in jaundiced neonates treated with phototherapy: role of intestinal secretion.

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.

Diarrhea, Infantile↗
PubMed1989

Characteristics and mechanism of action of a heat-stable enterotoxin produced by Klebsiella pneumoniae from infants with secretory diarrhea.

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.

Bacterial Toxins↗
PubMed1988

Unconjugated bilirubin and the bile from light exposed Gunn rats inhibit intestinal water and electrolyte absorption.

Jaundiced babies undergoing phototherapy often develop diarrhoea. The cause of it is still uncertain. Increasing evidence supports a role of a secretory mechanism for the diarrhoea. We therefore studied the effects of bile from congenitally jaundiced rats undergoing phototherapy and of unconjugated bilirubin on rat small intestine in vivo and in vitro. Results suggest that: (1) the bile from homozygous Gunn rats under phototherapy has an anti-absorptive effect when tested in the perfused jejunum of normal Wistar rats; (2) unconjugated bilirubin has a dose dependent secretory effect on the intestinal transport of water and electrolytes, when tested in the same system. Alteration of cyclic AMP or cyclic GMP, known intracellular mediators of secretion, was not observed. We conclude that free bilirubin is an intestinal secretagogue acting by an as yet unknown mechanism, that may mediate the secretory type of diarrhoea in jaundiced neonates undergoing phototherapy.

Animals↗
PubMed1988

Pathogenesis of postantibiotic diarrhoea caused by Clostridium difficile: an in vitro study in the rabbit intestine.

To elucidate the pathophysiological changes leading to postantibiotic diarrhoea caused by Clostridium difficile and its cytotoxin, oral ampicillin was given to rabbits, and jejunal, ileal, and caecal segments of those that developed diarrhoea were investigated in vitro. The rabbits that, in response to treatment, harboured Clostridium difficile in their colonic lumen were studied, and the results expressed according to the presence or absence of Clostridium difficile and/or its cytotoxin. Thus, we refer to either CD+ or CD- segments. The influx of glucose, phenylalanine, glycylphenylalanine, and lysine across the brush border of jejunum and ileum of CD+ segments was severely impaired, while only slightly blunted in CD-. No significant change was detected in the influx of glutamic acid in the jejunum of all treated animals and in the CD- ilea. Morphologic damage in ileum and caecum of CD+ was also more evident than in CD-. Transepithelial ion transport across short circuited ileal mucosa (CD+ and CD-) revealed secretory changes in Cl net transport that were more marked in CD-. We conclude that: (1) Clostridium difficile may also colonise the upper intestinal tract, where it induces morphological and functional damage, severely impairing nutrient absorption; and (2) the ileum contributes to the diarrhoea caused by CD even when the micro-organism is confined to the more distal gut by showing moderate impairment of nutrient absorption and marked electrolyte secretion.

Ampicillin↗
PubMed1988

Intestinal ion and nutrient transport in health and infectious diarrhoeal diseases.

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.

Communicable Diseases↗