[Prevalence of biliary lithiasis in chronic liver disease]. / Prevalenza della litiasi biliare in epatopatici cronici.

The prevalence of cholelithiasis was determined by ultrasound in 168 patients affected by chronic liver disease and compared to 828 subjects of the general population. We found an increase of cholelithiasis in chronic liver patients (p less than 0.004). This difference persisted separating the subjects in males (p less than 0.003) but not in females (p less than 0.08). Examined by age groups, patients demonstrated, like in the control group, an increase of frequency with the increase in age. We did not find any association with BMI, cholesterolemia, triglyceridemia, albuminemia and gammaglobulinemia levels. A significant association was found in the total (p less than 0.003) and indirect (p less than 0.0001) bilirubinemia. Finally, there was no significant association with the etiology of the liver disease. Even though there was a greater association with alcoholic and cryptogenetic liver disease.

[Serum PABA test in diabetes mellitus]. / Il PABA test sierico nel diabete mellito.

The serum values of para-amino-benzoic acid in subjects affected by type II diabetes mellitus, were measured hourly for 6 hours, after oral ingestion of B-T-PABA. These values were compared with those of a control group. The results demonstrate that at 1, 2, 4 and 5 hours, the mean values of the two groups were significantly different: p less than 0.01, p less than 0.002, p less than 0.0001 and p less than 0.005 respectively. Comparing the area under the curve the data did not differ significantly, indicating that at the end of the sixth hours the quantity of PABA absorbed is very similar in the two groups. These results indicate that patients with diabetes seem to have an altered exocrine pancreatic function, which may be due to a reduction in the zymogen stocked in the acinar cells or a lower secretory response to physiological stimulus. This impairment does not affect the digestion and the nutritional state of the patients.

Secretin-cerulein test and fecal chymotrypsin concentration in children with intestinal giardiasis.

We studied six patients with giardiasis (five males, one female), median age 3.5 yr (range 1-11) and 12 healthy control subjects (10 males, 2 females), median age 3.5 yr (range 1-10). Intestinal biopsy and a contemporaneous secretin-cerulein test were performed in all patients, and fecal chymotrypsin was also assayed. Intestinal biopsy was normal in five of the six patients with giardiasis, whereas one of the six presented a partial atrophy of the intestinal villi. The secretin-cerulein test (1 CU/kg of secretin + 75 ng/kg of cerulein) did not show any significant difference between values in the outputs of chymotrypsin, lipase, phospholipase, and bicarbonate obtained in patients and in controls; however, in the one patient with partial intestinal mucosal atrophy, all enzymatic activity levels were below the normal limit for our laboratory. Furthermore, the mean values of fecal chymotrypsin concentration did not differ between the two groups. Fecal chymotrypsin was also reduced in the patient with an abnormal secretin-cerulein test; a second assay performed 3 mo after the suspension of treatment (Metronidazole), however, showed a normal chymotrypsin concentration.

Evaluation of pancreatic function development after hydrolyzed protein-based and soy-based formulas in unweaned infants.

AIMS: Different protein sources could determine differences in the maturation of the exocrine pancreas in humans during the first months after birth; however, no studies have been carried out in man to evaluate the effect of a hydrolyzed protein diet on exopancreatic function. Our aim was therefore to determine the effect of two different milk formulas on pancreatic secretion in patients with cow's milk protein allergy (CMPA). METHODS: We selected 12 infants (median age, 3.0 months), fed for 6 weeks with a hydrolyzed casein-based formula, and 14 infants (median age, 3.0 months) who received a soy-protein based formula over the same period. As controls, two groups of age-matched infants with no gastrointestinal disease and receiving a free diet were studied. In the patients with CMPA a secretin-cerulein test was performed at the commencement of the diet and after 6 weeks; in the controls the same test was performed only once. Enzyme concentrations and outputs of trypsin, chymotrypsin, lipase, and phospholipase were assayed. RESULTS: No significant difference was observed between the two groups of patients with CMPA for any of the enzymes studied, either at base line or after 6 weeks of diet. No difference was recorded between CMPA patients and age-matched controls on a free diet either. In both CMPA groups there was a significant increase over basal values in trypsin, chymotrypsin, and lipase concentrations after 6 weeks. Furthermore, there was a significant positive correlation between the age of the patients and enzyme concentrations. Mean daily weight gain was 27.4 +/- 3.9 g with hydrolyzed casein and 27.2 +/- 3.5 g in soyfed patients. CONCLUSIONS: It is suggested that the diets with different protein content used in subjects with CMPA did not determine any difference in the stimulation of proteolytic and lipolytic pancreatic enzymes.

IgG anti-betalactoglobulin (betalactotest): its usefulness in the diagnosis of cow's milk allergy.

The aim of this prospective study was to evaluate the distribution of serum values of IgG anti-betalactoglobulin in 3 groups of subjects: a) 218 healthy subjects (138 M, 80 F) with age ranging from 1 month to 6 years; b) 205 patients with cow's milk protein allergy (CMPA) (130 M, 75 F) aged between 1 month and 4 years; c) 96 patients (50 M, 46 F) with symptoms compatible with CMPA, but suffering from other diseases (age range 1 month-6 years). The IgG anti-betalactoglobulin values were obtained using a new commercially available immunoenzymatic method. There was a marked difference in the distribution of IgG antibetalactoglobulin values in the 3 study groups. In healthy controls the value corresponding to the 5th centile was 5%, to the 50th centile 17%, to the 90th centile 48%. In the gastroenterological controls, 5th centile was 5%, 50th centile 15% and 90th centile was 56%. In the patients with CMPA, 5th centile was 27%, 50th centile 101% and 90th was 147%. The distribution of the values was therefore significantly different in the CMPA group from that of the other 2 groups (p < 0.0001). Plotting receiver operating characteristics curves, we have indicated a betalactotest value of 36% as a cut-off with the highest diagnostic accuracy (89% sensitivity, 85% specificity). We suggest that the betalactotest should be used to confirm diagnosis in patients with suspected CMPA; with a cut-off of over 48% we found only one false positive for diagnosis of CMPA in patients presenting other diseases with an identical clinical picture.

Severe infantile colic and food intolerance: a long-term prospective study.

To determine the relationship between infantile colic and cow's milk protein intolerance (CMPI) in formula-fed infants, 70 infants (38 male, 32 female) were selected, with mean age 30.2 +/- 21.4 days, with severe colic (duration of crying greater than 4 h per day for 5 days per week). In 50 of the infants in the study group (71.4%) there was a remission of symptoms when cow's milk protein (CMP) was eliminated from the diet. Two successive challenges caused the return of symptoms in all these 50 infants. There was a positive anamnesis for atopy in 9 of 50 of the patients with CMP-related colic and in 1 of 20 of those with non-CMP-related colic (p greater than 0.05). A follow-up period of 18 months' mean duration showed that 22 of 50 (44%) of the infants with CMP-related colic and 1 of 20 (5%) of those with non-CMP-related colic developed an overt alimentary intolerance (p less than 0.02). We conclude that a considerable percentage of the infants with severe colic also have CMPI and that in these cases, dietetic treatment should be the first therapeutic approach.

[Evaluation of the effectiveness of cisapride in the treatment of gastroesophageal reflux]. / Valutazione dell'efficacia della cisapride nel trattamento del reflusso gastro-esofageo.

To evaluate the effectiveness of administration of oral cisapride in patients with gastro-esophageal reflux, we studied 25 children, aged 1 month-7 years (mean 16.2 months) affected with GER. At the time of diagnosis and 8 weeks after treatment, patients were clinically evaluated and underwent a 24-hour continuous esophageal pH-monitoring. After treatment a complete regression of symptoms was observed in 20/25 patients. Moreover we recorded a significant reduction in the percentage of reflux time (p < 0.0001) and in the Jolley score (p < 0.0001), a very accurate scoring system to evaluate the pH-metric tracing, after treatment. It is concluded that cisapride is a useful agent both for the relief of symptoms and for the improvement of pH-metric parameters in children with GER disease.

Pancreatic insufficiency in celiac disease is not dependent on nutritional status.

To determine the relationship between pancreatic secretory capacity and nutritional status in celiac patients, we studied 52 patients with celiac disease (24 males, 28 females; age range 6-36 months) and 30 healthy control subjects (14 males, 16 females; age range 6-42 months). A secretin-cerulein test was performed on all patients, and levels of serum albumin and plasma fibronectin were assayed. In addition, weight/height ratios were calculated in the celiacs, who were then divided into three groups on this basis, as follows: celiacs with weight/height ratio < or = 3rd percentile; those with weight/height ratio between the 4th and 10th percentiles; and those with weight/height ratio > 10th percentile. There was no significant difference in the duodenal output of chymotrypsin, phospholipase and lipase between these groups. When the total celiac group was compared to control subjects, only lipase levels were significantly lower (P < 0.009). However, subnormal values in one or more pancreatic enzymes were observed in 15/52 celiacs (29%). A residual enzyme activity < 10% of normal secretory capacity, was also found in 4/52 patients. There was no correlation between the output of the various pancreatic enzymes and levels of albumin, fibronectin, and weight/height ratios in the patients. Furthermore, there was no difference in weight/height ratios and levels of albumin and fibronectin between the celiac subjects with pancreatic deficiency and those with normal pancreatic function. We conclude that a mild/moderate pancreatic insufficiency is quite frequent in celiacs, but that it may be completely independent of nutritional status; further studies are therefore required to shed light on its pathogenesis.

Pancreatic enzymes in chronic renal failure and transplant patients.

The aim of the present study was to determine the frequency and degree of elevated serum levels of Total Amylase (TA), Pancreatic Amylase (PA), and Lipase (L) activity in patients with chronic renal failure (CRF) on conservative therapy; CRF on periodical hemodialysis (HD); in renal transplant (RT) and in a control Group (C). Mean values were significantly higher in all groups than Group C for TA (p < 0.005), PA (p < 0.0001) and L (p < 0.0001). A statistically significant correlation was found between TA and L vs creatininemia values in CRF patients, but only up to a certain level (creatininemia < 6 mg %) (p < 0.03 and p < 0.05), above which there was no correlation. The enzyme most frequently over the maximum normal limit was PA, both in the total CRF group (51%), in the hemodialysis patients (65%), and in the RT patients (55%); but only a few patients had values two times higher than the normal limits: 15% in the total CRF, 14% is the hemodialysis, and 10% in the RT groups, respectively. These results suggest that the increase in serum pancreatic enzyme during chronic renal pathology is slight but frequently occurs. It is possible that in these patients together with the renal excretion impairment there could also be some subclinical pancreatic damage; its genesis could also depend on the pharmacological treatment used (diuretics, immunosuppressive drugs) commonly adopted in these pathologies.

Serum trypsin in chronic renal failure and transplant patients.

The frequency and degree of elevated serum levels of trypsin (T) and correlation with other pancreatic enzymes were determined in several groups of patients with renal disease, i.e., patients with chronic renal failure (CRF), hemodialysis patients (HD), renal transplant recipients (RT), and in a control (C) group. Mean values of T were significantly higher in all other groups than in the C group (p less than 0.0001). A statistically significant correlation between T and creatininemia levels was found only for the RT group (p less than 0.0001). Correlations between T versus pancreatic amylase and T versus lipase activity were found to be statistically significant in the CRF and RT groups (p less than 0.01), but not in the HD group. Most patients in all groups had T values higher than the maximum value observed in the controls and, of them, most had very elevated values. The results suggest that in chronic renal pathology there are frequent and significant increases in serum T levels, circulating in parallel with the other pancreatic enzymes. It is possible that, together with the renal excretion impairment, there could also be subclinical pancreatic damage or a dysfunction of the other means of elimination of T that can be responsible for, or contribute to, the serum increase in the enzyme.

Influence of haemodialysis on lipase activity.

Our aim was to determine whether the increase in serum pancreatic lipase values, reported in patients with chronic renal failure maintained on haemodialysis, is the result of haemoconcentration by fluid removal during dialysis, or whether it is due to lipase stimulation by endothelial lipoprotein lipase, induced by the heparin used as an anticoagulant. We therefore compared the increases in serum lipase, when heparin was used, with those observed when this was replaced by the antithrombotic agent, defibrotide, which has no effect on lipoprotein lipase. In addition, in order to determine the effects of haemoconcentration, variations in total protein concentration and haematocrit values were determined on the same samples, both before and after dialysis. The results showed a statistically significant post-dialysis increase in lipase only when heparin was used (p < 0.03). There was also a mean percentage post-dialysis increase of 16.2% in total protein (p < 0.0001) and 15.5% in haematocrit (p < 0.0001), due to fluid removal. No significant correlation in percentage increases was found between lipase vs total protein or haematocrit values. These findings suggest that heparin-induced lipoprotein lipase stimulation is the principal cause of the post-dialysis increase in pancreatic lipase, and that fluid removal during dialysis makes only a minor contribution to this increase.

Gastroesophageal reflux and cow's milk allergy in infants: a prospective study.

BACKGROUND: Recent reports have suggested that gastroesophageal reflux in pediatric patients may be caused by food allergy. OBJECTIVE: The aim of our study was to determine the frequency of the association of gastroesophageal reflux with cow's milk protein allergy in patients win the first year of life. METHODS: We studied 204 consecutive patients (median age, 6.3 months) who had been diagnosed as having gastroesophageal reflux on the basis of 24-hour continuous pH monitoring and histologic examination of the esophageal mucosa. RESULTS: Clinical history suggested diagnosis of cow's milk allergy in 19 infants, and 93 others had positive test results (serum IgE anti-lactoglobulin, prick tests, circulating or fecal or nasal mucus eosinophils) but did not have symptoms indicating cow's milk allergy. The cow's milk-free diet and two successive blind challenges confirmed the diagnosis of cow's milk allergy in 85 of the 204 patients with gastroesophageal reflux. The clinical presentations of the infants with gastroesophageal reflux alone were different, in view of the greater frequency of diarrhea (p less than 0.0001) and atopic dermatitis (p less than 0.0002). In all, gastroesophageal reflux was associated with, and probably caused by cow's milk allergy, in 85 of 204 cases (41.8%). CONCLUSIONS: Considering the frequency of this association, patients younger than 12 months old with symptoms of gastroesophageal reflux should be carefully examined to determine whether this disorder is primary or caused by cow's milk allergy.

Pancreatic enzyme therapy in childhood celiac disease. A double-blind prospective randomized study.

The validity of pancreatic enzyme substitution therapy in the two months following diagnosis of celiac disease was investigated. Twenty patients (8 males, 12 females), mean age 14.2 months (group A) received an enzyme substitution preparation. The control group (group B) included 20 patients (9 males, 11 females), mean age 14.5 months, treated with placebo. Before starting treatment, we performed a stratification for age, weight-for-age at diagnosis, and degree of pancreatic insufficiency. The therapies were then administered randomly in double-blind fashion. On diagnosis and 30 and 60 days after commencement of a gluten-free diet with identical calorie intake in both groups, a series of anthropometric variables were determined. After 30 days weight increase in group A patients was significantly higher (in grams) than in group B: 1131 +/- 461 vs 732 +/- 399 (P < 0.006). Weight-for-age increase also was greater in group A than in group B: 9.2 +/- 5.1% vs 5.0 +/- 4.0% (P < 0.002). The increase in height Z score, weight-for-height, arm circumference, and subscapular and tricipital fold measurements were greater in group A patients than those in group B, but the difference was not significant. After 60 days of therapy none of the parameters considered were significantly different in the two groups. We concluded that pancreatic enzyme therapy is certainly useful in the first 30 days after diagnosis of celiac disease.

Gastric emptying in infants with gastroesophageal reflux. Ultrasound evaluation before and after cisapride administration.

The present study aimed to evaluate gastric emptying in children with gastroesophageal reflux (GER) by means of real-time ultrasonography, on the basis of measurements of the cross-sectional area of the gastric antrum. Twelve children with GER were studied (seven males, five females; age range, 3-13 months) and compared with 12 normal control children (six males, six females; age range, 3-13 months). The diagnosis of GER was confirmed by 24-h esophageal pH-monitoring. The GER patients had a significantly greater antral area than the controls at 90, 105, and 120 min after eating a standard meal (cow's milk formula, 300 ml/m2 body surface area); in addition, final gastric emptying time was significantly greater in the patients than in the controls (145 +/- 36.9 versus 78.7 +/- 19.3 min; p less than 0.0025). After 8 weeks of treatment with cisapride (0.3 ml/kg, three times a day) 24-h esophageal pH-monitoring and ultrasonography studies were repeated in the patients. The total percentage reflux time was significantly lower (p less than 0.038), and ultrasonography showed a decreased antral area at all the various study times, with no significant difference between patients and controls; final gastric emptying time was also significantly lower than before treatment (p less than 0.009). Furthermore, in the GER patients there was a significant correlation between gastric emptying time and the sum of the various reflux times recorded in the 2 h after all meals over the 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of 24-hour oesophageal pH-metry for the detection of gastro-oesophageal reflux in infants: what is the ideal score and the optimal threshold? A receiver-operating-characteristic analysis.

BACKGROUND: The search for the ideal score and best cut-off value to interpret the data from 24-hour continuous pH-monitoring interests both gastroenterologists with adult patients and paediatric gastroenterologists. AIMS: To evaluate 24-hour continuous pH monitoring as a discriminatory test in the diagnosis of gastro-oesophageal reflux disease in a paediatric population, using various pH-metry scores and cut-off values. PATIENTS: One hundred and one patients presenting gastro-oesophageal reflux disease (endoscopic diagnosis of oesophagitis or coincidence between apnoea and reflux episodes observed during pH-metry), median age 10 months, were studied, together with a control group of 84 subjects, median age 11 months. RESULTS: After plotting the receiver operating characteristic curves and calculating the area below them, the evaluation of the total percentage reflux time proved to have a higher capacity for distinguishing between the patients and controls than the Euler score (p < 0.05). The cut-off value of 5.2% for the total percentage reflux time had a sensitivity of 75% and was 88% specific. Using higher cut-off values according to age, a 95% specificity and a 49% sensitivity were obtained. The most sensitive score was the Jolley score: 96% with a cut-off of 64 and 90% with a cut-off of 100 (a value determining the maximum diagnostic accuracy); specificity, however, was low: 39-61%. In addition, the Jolley score was the most useful parameter in detecting patients with apnoeic episodes secondary to gastro-oesophageal reflux disease and allowed a correct diagnosis in 12/13 cases. CONCLUSIONS: a) The simple determination of total percentage reflux time, according to the methodology used, has a higher predictive capacity than the more complex pH-monitoring scores; b) the best cut-off value for total percentage reflux time is 5.2% as it combines a good specificity and sensitivity which are necessary for this test; c) age-dependent cut-off values are highly specific but sensitivity is much too low; d) the Jolley score is very sensitive and this was maintained even when the cut-off was raised to a value of 100; it is the best predictive score for episodes of gastro-oesophageal reflux-dependent apparent life-threatening events.