The value of anti-Helicobacter pylori IgG antibodies in establishing eradication of infection in children.

The aim of this study was to evaluate the performance of anti-Helicobacter pylori (H. pylori) IgG antibodies in monitoring eradication of infection in children. Forty-seven H. pylori-infected children (aged 12.5 +/- 3.0 years, range 6.5-18 years) were followed for a mean of 30.3 months (range 6.66 months). Patients were divided into those with eradicated infection and those with ongoing infection, as determined by antral biopsy-related tests (histology, urease and culture). Anti-H. pylori antibodies (EIA) were tested at diagnosis and follow-up and changes of antibody titers were compared between the two groups. Twenty-five of 26 non-eradicated patients showed persistently high levels of antibodies throughout the study. One patient had non-detectable antibodies despite an ongoing infection for 12 months. Patients with eradicated infection showed a progressive fall of antibody levels from 52.9 +/- 32.4 U/ml at diagnosis to 17.5 +/- 4.1 U/ml at 6 months (p < 0.007) and 4.4 +/- 0.7 U/ml at > or = 12 months (p < 0.002). In 17 of 21 eradicated patients, serum antibodies normalized during the follow-up period; in 4 of the 21 patients, a decrease of > or = 40% of the initial value was observed during the 8-month follow-up. The validity of serology in the evaluation of H. pylori infection had a sensitivity of 100%, specificity of 96% and positive predictive and negative predictive values of 95% and 100% respectively. Our conclusion is that serial determination of anti-H. pylori antibodies is a reliable method for the follow-up and monitoring of H. pylori eradication in children and adolescents.

Serum pepsinogen I in childhood Helicobacter pylori gastritis: its relation to mucosal peptic activity.

Serum pepsinogen I (PG I) levels are raised in children with Helicobacter pylori gastritis. To ascertain if this is due to increased production or to increased secretion of pepsin by chief cells, we measured mucosal peptic activity in antrum and gastric body mucosal homogenates and correlated it to serum PG I levels in 122 children with and without H. pylori gastritis. In patients infected with H. pylori, mucosal peptic activity was decreased when compared to control and to children with non H. pylori gastritis. Serum PG I levels were increased (P < 0.001) and were inversely related to mucosal peptic activity (P < 0.01). These findings suggest that H. pylori can promote a leakage of pepsinogen into the circulation.

Colchicine enhances intestinal permeability in patients with familial Mediterranean fever.

OBJECTIVE: Colchicine therapy is complicated by frequent gastrointestinal adverse effects. METHODS: We compared intestinal permeability in 21 patients with familial Mediterranean fever on long-standing colchicine therapy (mean 5.8 years) and significant gastrointestinal complaints and 12 untreated patients and 14 healthy volunteers. The double probe (lactulose/mannitol) permeability test was performed using a hyperosmolar test solution (1580 mosmol) and the differential urinary recovery ratios were calculated. RESULTS: Familial Mediterranean fever patients on colchicine therapy had significantly higher lactulose/mannitol urinary excretion ratios (0.073) compared to untreated patients (0.035) and to healthy controls (0.021). Untreated familial Mediterranean fever patients had significantly greater urinary lactulose/mannitol recovery ratios than controls (P < 0.02). No correlation was found between the degree of enhanced permeability and the length of exposure to the drug or the severity of clinical symptoms. CONCLUSIONS: Intestinal permeability was significantly enhanced in patients with familial Mediterranean fever treated with colchicine.

Basal and activated intracellular calcium ion concentrations in mononuclear cells of Alzheimer's disease and unipolar depression.

We present the results of a case control study on the concentration of intracellular calcium [Ca+2]i in peripheral blood mononuclear cells (PBMC) of patients with Alzheimer's disease (AD), major affective disorder unipolar type (DEP), and elderly controls. We used the fluorescent dye Quin-2 to measure intracellular calcium concentration in PBMC both in their basal resting state [Ca+2]b and after activation [Ca+2]a with phytohemagglutinin (PHA). The [Ca+2]b and [Ca+2]a values in PBMC of AD patients were significantly higher than those of the elderly controls and of the DEP patients. In the DEP patients the [Ca+2]a values in PBMC were significantly higher than those of the elderly controls, but the [Ca+2]b values were not. [Ca+2]i levels did not correlate with age, gender, or duration and severity of the diseases investigated. These findings indicate that higher values of [Ca+2]b and [Ca+2]a may differentiate most AD patients from elderly controls or DEP patients.

Colchicine induces enhanced intestinal permeability in the rat.

Intestinal permeability was determined in rats receiving colchicine 0.5 +/- 0.15 mg day-1 in drinking water (30 mg L-1) for periods up to 23 days. The lactulose/mannitol method was used to determine whole gut permeability before and on days 2, 4, 8, 18 and 23 of colchicine administration. The 8-h urinary lactulose excretion following the test meal increased significantly in rats receiving colchicine, compared with the pretreatment value. Increased lactulose permeability was present after 2 days and remained stable throughout the experimental period. Mannitol urinary excretion was not changed. Colchicine increases intestinal tight junction permeability by an as yet undetermined mechanism.

Uptake of serotonin into platelets of senile dementia of the Alzheimer type patients.

[3H]-serotonin uptake in platelets was studied in 26 patients with senile dementia of the Alzheimer type (SDAT), 29 age-matched normal elderly persons, and 21 young subjects. The results showed a significantly lower uptake of serotonin into platelets of SDAT patients than in those of elderly controls (p < .02). Uptake of serotonin into platelets of elderly normal subjects was significantly lower than in the young (p < .01). These differences were due to reduced Vmax, whereas Km was unchanged. Isolated plasma from SDAT patients did not affect the uptake of serotonin into platelets of elderly controls, and vice versa, i.e., plasma obtained from elderly controls did not affect serotonin uptake in SDAT patients. The results indicate that serotonin uptake into platelets is reduced in normal aging, and more so in SDAT. Moreover, the reduced uptake in SDAT is not caused by a plasma factor in SDAT patients. No correlation was found between serotonin uptake and degree of cognitive impairment in SDAT patients.

Mucosal peptic activity during Helicobacter pylori infection in pediatric patients.

Intramucosal peptic activity may participate in the genesis of acute and chronic superficial gastritis. The proteolytic activity of homogenates of gastric mucosa (antrum and body) and duodenum were measured at pH 2.0 (total peptic activity) after exposure to pH 8.0 (pepsinogen) and the activated pepsinogen (pepsin) was calculated in pediatric patients investigated for the presence of Helicobacter pylori (H pylori), 122 antral, 77 stomach body, and 74 duodenal biopsies were examined in 43 H pylori positive patients, 51 controls, and 28 H pylori negative gastritis patients. Activated pepsinogen was significantly reduced in the stomach of H pylori positive patients only. Pepsinogen values were similar in all the anatomical areas tested in all patients. In 13 H pylori positive patients reinvestigated three months after antibiotic therapy, antral mucosal activated pepsinogen activity increased significantly (mean pretreatment 1.56 (1.0) U/mg protein versus mean post-treatment 2.72 (1.7) U/mg protein) and reached values comparable with controls. The decreased activated pepsinogen activity in association with normal pepsinogen content observed in the antrum of H pylori positive gastritis patients indicate local pepsin inactivation or alternately enhanced removal into the gastric lumen or backflow into the circulation.

Adaptive response of ileal mucosa to malnutrition in the rat: role of polyamines.

Mucosal disaccharidases and ornithine decarboxylase activities were measured in malnourished, preweaning (19 days), post weaning (24 days) and young adult (37 days) rats. Malnutrition resulted in decreased body weight, intestinal weight, DNA and protein content. Mucosal Prot/DNA ratios were elevated in the ileal segments of the 24 and 37 day rats. Preweaned malnourished rats had significantly enhanced lactase specific activity in both jejunal and ileal segments. Adult malnourished rats showed enhanced jejunal lactase and sucrase activities which were not accompanied by elevated ornithine decarboxylase values. Mucosal sucrase and ornithine decarboxylase specific activities were significantly elevated in the ileal segment of the 24 and 37 day old malnourished rats. Studies of adult rats showed that these increased specific activities were located in the mature enterocytes at the villus tip, and persisted during a 24 h diurnal cycle. DFMO administration for 4 days completely inhibited mucosal ornithine decarboxylase and abolished the rise of ileal sucrase activity. We concluded that the intestinal response to reduced food intake is age related and differs in the jejunum and ileum: ornithine decarboxylase and polyamines are involved in ileal adaptation to malnutrition in postweaned and adult rats.

The effect of post-natal malnutrition on pepsinogen secretion receptors in weanling rats.

Post-natal malnutrition was induced in rats using the expanded litter model. Pepsinogen secretion of isolated gastric glands in response to several secretagogues was measured. Malnourished 19-day-old pups showed no response to carbachol, CCK-8, gastrin, secretin and ionophore A23187 compared to well-nourished animals, but showed comparable secretion of pepsinogen after stimulation with dibutyryl cAMP (DiBcAMP). Hydrocortisone treatment for 48 h caused increased pepsinogen accumulation and elevated pepsinogen secretory responsiveness to carbachol and secretin of gastric glands isolated from post-natal malnourished pups. Our results indicate that isolated gastric glands obtained from well-nourished rat possess two functionally distinct receptors for gastrin and C-terminal fragment of CCK. Our study supports the concept that in malnourished rats there is a decreased number of binding sites or/and some post-receptor defects. Pepsinogen release mechanisms remain unaffected.

Bile acid sequestration by the solid phase of stools in cystic fibrosis patients. Role of pancreatic enzymes.

The distribution of bile acids in the stool of seven cystic fibrosis (CF) patients with severe or mild steatorrhea was examined and compared with that of three controls. Results indicated significantly lower endogenous bile acid concentrations in the stool water phase, obtained by centrifugation, in the CF patients (12.0 +/- 3.5%), compared with the controls (25.5 +/- 8.1%). In vitro incorporation of labeled cholic acid (CA) and deoxycholic acid (DCA) demonstrated a stronger binding of both to the particulate matter of stools in the CF group. Using equilibrium dialysis, the calculated concentrations of unbound CA and DCA in the CF group measured 0.78 and 0.3 mumol/g homogenate, respectively, and in the control patients 1.76 and 1.39 mumol/g homogenate, respectively. Partial release of bile acids from CF stool pellets was achieved by the addition of trypsin and elastase, as well as by alkalinization. It is suggested that in patients with CF, stool bile acids are bound to the undigested protein fraction, which makes them unavailable for colonic resorption.

Effects of the components of breast milk on mucosal enzyme activity of the newborn small intestine.

The effects of the aqueous phase of human breast milk on the disaccharidase activity of newborn rabbit small intestinal mucosal explants were studied in vitro culture. These explants continuously synthesized protein and normal morphology was maintained for the duration of the cultures. Addition of the aqueous phase resulted in significant increase of lactase (p less than 0.001) and maltase (p less than 0.01) concentrations in these organ cultures. This effect was dose dependent and was observed whether the organ biopsies were derived from fed or starved newborn rabbits. Further purification of the aqueous phase showed that the active ingredient exerting these effects was lactose. These studies suggest that lactose may have an important function in stabilization of newborn intestinal disaccharidase enzymes.

Well-compensated primary bile acid malabsorption presenting as chronic nonspecific diarrhea.

Increased fecal bile acid loss and defective in vitro ileal bile acid uptake were demonstrated in an 8-year-old boy with diarrhea starting in the neonatal period. His continuously normal physical development and good nutritional status are in keeping with a well-preserved cholic acid pool and normal duodenal bile acid concentration. Isolated bile acid malabsorption can remain well compensated and present as the chronic nonspecific diarrhea syndrome of childhood.

Stool output and composition in the chronic non-specific diarrhoea syndrome.

Stool output and composition were studied in 7 children with chronic, non-specific diarrhoea syndrome and the results were compared with those of children with malabsorption due to cystic fibrosis or to bacterial overgrowth syndrome, and with stools from controls. Daily quantities of stool, fat, and total bile acids were normal in patients with chronic, non-specific diarrhoea syndrome. Faecal sodium concentration was high compared with that of controls or patients with cystic fibrosis. The extractable water phase of stools appreciably increased in patients with chronic, non-specific diarrhoea syndrome and contained 50% of the total stool bile acids; this was also the case in patients with bacterial overgrowth syndrome. It is suggested that a secretory state of the large-bowel due to mucosal exposure of large quantities of bile salts in the extractable water phase may be contributory to the diarrhoea of chronic, non-specific diarrhoea syndrome.

Disturbed fat absorption following infectious gastroenteritis in children.

Fat absorption was studied in 10 patients recovering from an episode of acute infectious gastroenteritis who failed to gain weight despite adequate caloric intake. Three patients restudied after clinical improvement and three other infants with failure to thrive, unrelated to gastrointestinal problems, served as control subjects. Fat balance studies during the ingestion of a formula containing long-chain fatty acids demonstrated significant degrees of steatorrhea in patients (mean CFA 70.6 +/- 10.7 compared to 90.3 +/- 2.4 in control subjects). The administration of a test meal demonstrated a marked deficiency of duodenal bile acid concentration and of fat incorporation into the micellar phase in patients. Fecal bile acid excretion was significantly increased in patients (mean 33.9 +/- 11.6 microM/kg/day) as compared to control subjects (mean 13.5 +/- 3.1 microM/kg/day). Bacterial overgrowth and abnormalities of the small intestinal mucosa were not constant. Ileal dysfunction and associated bile acid loss are possible causes of disturbed fat assimilation following acute intestinal infection in children.