Artificial feeding: progresses and problems.

The introduction of infant formulas represents an important result in the field of the newborn and infant artificial feeding, reducing the gap with maternal feeding. In the last decade technological evolution allowed to obtain milk formulas which became more and more similar to human milk starting from cow's milk, thus obtaining a composition adequate to the digestive and nutritional requirements of the newborn and of the infant, starting from the model of the breast feeding (infant formulas). The major differences between human and cow's milk have been corrected by dilution, skimming, addition of carbohydrates, acidification. From an allergenic viewpoint, in a recent study, we observed that no significant differences can be observed in the development of atopic symptoms for children supplemented with different substances in the first 5 days of life or receiving cow's milk infant formulas in the first three months of life, compared to those breast fed. In the case of the development of intolerance or allergy to cow's milk proteins, the substitution of the cow's milk based formula with hydrolysed or soy formulas is required. Maternal feeding represents the best choice for the nutrition of the newborn; however, when it is not possible, milk formulas despite they still show marked differences with human milk, concerning both nutrients and defensive factors, allow to reach satisfactory results about both nutrition and health.

Reflux esophagitis in children: a scanning and transmission electron microscopy study.

In children, excess of gastroesophageal reflux causes lesions of the esophageal mucosa that we have studied by scanning and transmission electron microscopy (SEM and TEM respectively) in 27 grasp biopsies prelevated during endoscopic procedures. Ultrastructural lesions can be graded on the basis of their severity. In grade I, epithelial cells are well preserved in the deepest layers whereas the superficial cells display ultrastructural alterations such as irregular microridges or reduced intercellular junctions. In grade II, the surface is composed of extruding cells and in the intermediate layer, large intercellular spaces containing lympho-monocytic cells are visible. In grade III, the mucosal surface is characterized by crater-like erosions, degenerating cells are visible in all the layers; in two patients columnar epithelium-lined areas (Barrett's esophagus) have been identified. Our results suggest that in patients with reflux esophagitis, ultrastructural examination of grasp biopsies prelevated by pediatric endoscopes allows a grading of the anatomical lesions providing data that can not be obtained by conventional histology.

Surfactant-like material in the antral gastric mucosa of children.

It has been proposed that the hydrophobicity of the gastric mucosa is due to surfactant-like material (SLM), mainly composed of phospholipid, adsorbed to the mucosal surface. Biochemical and physiological studies have been performed in different mammals but morphological data on children are lacking. In the present work, the presence of SLM on the antral gastric mucosa of children has been studied by electron microscopy. The results demonstrate that SLM is present and shows two different forms, lamellar bodies and lamellar layers. In the mucosae without endoscopic, histologic, and ultrastructural alterations we have found SLM when the tannic acid method has been used but not when the tissue has been fixed only in glutaraldehyde. Our results suggest that in children with ultrastructural alterations of the epithelium, the amount of gastric SLM is increased in respect to children with a normal mucosa and that the amount of SLM on the surface of the gastric antral mucosa is modified in pathologic conditions.

Peptic disease in paediatric patients: a diagnostic and therapeutic contribution.

A retrospective clinical study was conducted in 267 children referred to the Verona University Institute of Paediatrics over the period from June 1985 to May 1989 for peptic symptoms. The aim was to obtain data on the incidence of peptic disease in paediatric patients and on the efficacy of various types of pharmacological active principles in treatment of the acute phase and of relapses. All cases observed were subjected to endoscopy (also combined with biopsy in cases presenting signs of inflammatory ulcer disease), which revealed the presence of mucosal abnormalities in 125 patients (46.8%), diagnosed as follows: oesophagitis (44 cases), gastritis and duodenitis (73 cases) and peptic ulcer (8 cases). Among the drugs used, ranitidine proved highly effective, producing healing in all cases reporting for follow-up, and showed excellent tolerability.

Biotin-responsive infantile encephalopathy: EEG-polygraphic study of a case.

A case of an infant suffering from progressive lethargy, sparse scalp hair, autistic-like behavior, myoclonias, and drug-resistant generalized seizures is reported. Laboratory investigations revealed, in the absence of metabolic acidosis, an increased urinary excretion of 2-ketoglutaric acid and a small peak of 3-hydroxyisovaleric acid. The serum biotinidase activity was 0.15 nmol min-1 ml-1 (normal range 5.2 +/- 0.9) in the propositus and 0.310 and 0.420 in her father and mother, respectively. The interictal EEG showed multifocal abnormalities; numerous seizures were recorded, with the pattern of true tonic-clonic fits, exceptional in infancy. Also myoclonias, auditory myoclonus, and repetitive startles were documented. Because of dramatic improvement of all symptoms and signs after starting biotin (5 mg twice daily), the authors suggest a therapeutical trial in all drug-resistant infantile seizures.

Neonatal screening for biotinidase deficiency in north eastern Italy.

Biotinidase deficiency satisfies all the criteria for incorporation into neonatal mass screening programmes for inborn errors of metabolism. We report our preliminary experiences with screening of 24,300 newborns during a 6 month-period when 1 infant with biotinidase deficiency was detected. On the basis of these results, this disorder appears to be as common as other well known metabolic disorders for which mass screening is available.

Efficacy and duration of action of placebo responses in the prevention of exercise-induced asthma in children.

Exercise-induced bronchoconstriction, a common phenomenon in asthmatic children, may be prevented by the administration of appropriate drugs. In this study we evaluated the effect and duration of action of placebo (Freon gasses) administered to the patients as a protective drug. The maximum decrease in forced expiratory volume in 1 second (FEV1) after exercise testing was 40.3% +/- 3.10 at the initial screening session and, on different study days, 23.3% +/- 3.57, 28.8% +/- 3.86, and 33.7% +/- 3.71 30, 120, and 240 minutes, respectively, after the administration of Freon gasses. There was a linear trend indicating a reduction in protection with time. The placebo effect was marked 30-120 minutes after treatment (p less than 0.01) and completely disappeared after 4 hours. The placebo effect should always be considered in the evaluation of any new antiasthmatic drug.

Behaviour of some lysosomal enzymes in the plasma of insulin dependent diabetic patients during artificial pancreas treatment.

The plasma levels of three lysosomal enzymes, beta-D-N-acetylglucosaminidase, beta-D-glucuronidase, and alpha-L-fucosidase, were fluorimetrically determined in seven insulin-dependent diabetic patients one day before, one day after, and during a two-day treatment with the artificial pancreas, at 4 to 5 h intervals. A statistically significant decrease of the plasma level of each enzyme was observed during artificial pancreas treatment. The extent of decrease was 30 to 35% for beta-N-acetylglucosaminidase, 35 to 40% for beta-D-glucuronidase, and 20 to 25% for alpha-L-fucosidase. The decrease occurred earlier (at the first day of treatment) for beta-D-N-acetylglucosaminidase, and later (at the second day of treatment, and lasting to the first day after treatment) for the other two enzymes. These results suggest a direct connection between the lysosomal apparatus and insulin-controlled metabolic pathways, and a potential role for lysosomal enzymes as indicators of the metabolic compensation in diabetes.

Salbutamol and ipratropium bromide solution in the treatment of bronchospasm in asthmatic children.

The effects of the beta 2-adrenergic agonist salbutamol (0.02 mL/kg of a 0.5% solution) and the cholinergic antagonist ipratropium bromide (2 mL of a 0.025% solution), administered alone or in combination at different doses, were evaluated in 48 asthmatic children using a single-dose, double-blind, crossover design. Spirometric measurements were taken before and 10, 30, 60, 120, 180, 240, 300, and 360 minutes after administration of the drugs. All regimens produced significant bronchodilatation 10 to 30 minutes after administration. The improvement began to decline three to four hours after inhalation, particularly when ipratropium bromide was administered alone. The administration of the salbutamol plus ipratropium combination did not significantly improve pulmonary function values as compared to salbutamol alone. The effects of salbutamol and ipratropium bromide in half-dose or full-dose combinations were indistinguishable. No significant adverse effects on blood pressure or heart rate were observed.

Synthetic growth hormone-releasing hormone (GHRH 1-44) in the differential diagnosis between hypothalamic and pituitary GH deficiency.

GH response to an iv bolus of growth-hormone-releasing hormone (GHRH 1-44, 2 micrograms/kg iv) was evaluated in 17 prepubertal children with total GH deficiency (GHD), 6 with partial GHD and in 7 prepubertal normal but short children tested as control. GH response to conventional pharmacological (insulin and arginine or L-Dopa) and physiological stimuli (sleep test) and to GHRH test was also compared. GHRH-induced GH peak occurred at variable times and marked heterogeneity in magnitude of the individual responses to this peptide was observed in GHD patients and in controls. GH increases after GHRH with a peak greater than 10 ng/ml suggested an hypothalamic origin of the GHD in 12 patients (8 with total GHD and 4 with partial GHD). A significant difference (p less than 0.025) of GH peak mean following GHRH administration between total GHD children and normal short children was found. GH response to GHRH injection was usually higher than to conventional stimuli. Nevertheless GH peak following GHRH administration was lower than GH peak following conventional stimuli in 6 children (2 partial GHD children and 4 normal ones). A normal short child failed to respond to GHRH test performed twice. GHRH test is an important diagnostic tool in order to point out hypothalamic GHD.

Simplified spinhaler method for antigen-specific bronchoprovocation in children with bronchial asthma. I.

Specific bronchial challenge has been performed using a micronized, freeze-dried allergen extract of D. pteronyssinus administered as a powder at increasing concentrations (0, 50, 100, 200, 400, 600, 800, and 1,000 Allergenic Units) by a cromolyn spinhaler delivery system. The test was performed in ten asthmatic children with house mite D. pteronyssinus skin test and RAST positivity and in six non-allergic asthmatic children. A positive early reaction to bronchial challenge occurred in eight out of ten allergic children. A ninth child of this allergic group presented only the late reaction. Five patients of the control group (skin test and RAST negative for D. pteronyssinus had negative results while one child had a positive response both with early and late reactions. A significant increase in methacholine sensitivity was observed in the allergic group the day following the specific challenge. The modified spinhaler procedure (Hypoinhal, Lofarma) used for specific bronchial challenge showed a good correlation with skin test and RAST positivity in patients as well as in the control population. The method provides advantages of simplicity, ease of performance and cost effectiveness.

Comparative study of two methods for spinhaler-specific bronchoprovocation challenges. II.

Two different methods of performing specific bronchial challenge using a micronized freeze-dried extract of D. pteronyssinus administered as a powder by a spinhaler have been evaluated in 11 children with chronic asthma and skin test RAST positive for house dust mite D. pteronyssinus. In the first method, "Cumulative Dose Method" (CDM), the test doses of antigen [0, 50, 100, 200, 400, 600, 800, and 1,000 Allergenic Units (A.U.)] were successively administered in 30-minute intervals. With the other method, "Daily Increasing Dose Method" (DIDM), a single antigen challenge (only one cup) was performed every day successively. The tests were considered positive when FEV1 values dropped below 20% of the value obtained immediately before the inhalation of the antigen. The early FEV1 fall was 36.6% +/- 10.8% with CDM and 29.1% +/- 11.5% with DIDM. There was a mean late fall of FEV1 52% +/- 17% and 35.3% +/- 12.2%, respectively, after a mean antigen administration of 270 +/- 149 A.U. with CDM and of 290 +/- 202 A.U. with DIDM. An increase in non-specific bronchial reactivity was observed after specific challenge performed with both methods. The CDM offers the advantage of obtaining information more quickly. The DIDM offers the advantage of administering a lower daily dose of antigen. Our results indicate that a modification of CDM with a shorter interval of administration may further improve this method of antigen administration.

Serum enzymes of lysosomal origin as indicators of the metabolic control in diabetes: comparison with glycated hemoglobin and albumin.

Several lysosomal enzymes (beta-N-D-acetylglucosaminidase, beta-D-glucuronidase, alpha-D-galactosidase, beta-D-galactosidase, alpha-L-fucosidase, alpha-D-glucosidase, alpha-D-mannosidase, beta-D-glucosidase), glycated albumin and glycated hemoglobin (HbA1c) were determined in the serum of 81 insulin-dependent diabetics with different degrees of metabolic control (optimal, 21 patients; good, 39 patients; poor, 21 patients) and without signs of complications, and in 42 control subjects. All parameters examined increased in serum in inverse proportion to the degree of metabolic control. A highly significant correlation (p less than 0.01) was found between lysosomal enzymes and both glycated albumin and HbA1c. All parameters correlated with hyperglycemia, glycated albumin having the highest r-value (0.586) and lysosomal enzymes the lowest one. Unlike glycated albumin and HbA1c, serum levels of lysosomal enzymes in patients with optimal metabolic control were undistinguishable or even lower than those of controls. A 2-month longitudinal monitoring of a patient who was hospitalized in conditions of poor metabolic control and adequately treated, proved that lysosomal enzymes diminished in serum parallel to glycated albumin and HbA1c in relation to improvement of the metabolic situation. The conclusion is drawn that serum lysosomal enzymes are good indicators of the metabolic control of diabetic patients probably reflecting the overall metabolic state connected with insulin action rather than hyperglycemia.

Comparison of two new controlled-release theophylline formulations in the management of asthma in children and reliability of salivary theophylline concentration.

Two slow-release preparations of theophylline have been compared in an open crossover trial in the treatment of 20 asthmatic children. Theophylline concentrations were measured in both serum and saliva. Although the treatment preference of both patients and clinicians was for Somofillina Ritardo, there was no significant difference between the two treatments in respect to either serum and salivary concentrations. Nor did their mean bioavailabilities differ significantly. The results indicated that concentration in saliva was not a useful indicator of the serum concentration.

Preliminary report on histamine release, circulating immune complexes, and complement activation in children with atopic dermatitis after oral challenge with milk and egg antigens.

The effects of dietary restriction and food challenge were evaluated in five children with atopic dermatitis, as a possible predictive marker for the dietary management of this clinically perplexing disease. Two of the five showed significant elevation of plasma histamine; an additional two demonstrated the presence of immune complexes and in the fifth no change was described. The results of these study lend further support to the causal relationship between food allergy and atopic dermatitis, and suggest that the use of these immunologic parameters may be useful in the clinical assessment and management of these patients.

Pulmonary function and bronchial hyperreactivity in asthmatic children with house dust mite allergy during prolonged stay in the Italian Alps (Misurina, 1756 m).

The effects of high altitude were evaluated in 14 children with allergic bronchial asthma over an 8-month period. Clinical improvement, as assessed by decreased bronchial lability, was demonstrated by pulmonary function studies. There was a decreased requirement for drugs and steroids were discontinued in our children. The results of this study suggest the use of this approach as a possible adjunct to the management of refractory cases of bronchial asthma.

Inhibition of exercise-induced asthma by three forms of sodium cromoglycate.

Fifteen asthmatic children were tested in a double-blind fashion. The degree of prevention of exercise-induced asthma by three pharmacological forms of sodium cromoglycate (SCG with lactose powder, SCG in micropellets without lactose and SCG solution) was evaluated. FEV1 and FEF 25-75 were measured. Inhibition of the airway response to exercise was achieved by SCG without any statistical differences between the three active forms. Our data suggest that the new pelletised form of SCG without lactose is as active as the other preparations of the drug. The easy mode of administration allows a high compliance of the young asthmatic patients to chronic therapy.

A longitudinal study on plasma somatomedin activity in full-term, preterm and small-for-gestational age newborns.

Plasma somatomedin (SM) activity was measured longitudinally in the first days of life by Van den Brande bioassay in 10 term, 8 premature and 5 small-for-date newborns. Other term, premature and small-for-date newborns were assayed between the 4th and 8th days by a cross-sectional-type study. A very significant increase in SM activity was observed in term newborns on the 3rd day lasting for about a week, when values usually observed in young children were reached. In premature and small-for-date newborns such an increase was not present but rather a slight decrease on the 3rd day was observed. The presence of a circulating inhibitory substance in the plasma of premature and small-for-date newborns with undetectable SM activity was shown.