[On vaccination against measles with a live and attenuated virus (Schwarz strain) in a nursery school. Resistance to natural infection (author's transl)].
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Biomedical subjects
Publications and source records attributed to A Battistini.
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The 4 diagnostic stages of Cystic Fibrosis (C.F.) will be dealt with: prenatal diagnosis, singling out of the heterozygotes, clinical diagnosis and finally, the instrumental confirmation with the sweat test. The techniques for the intra-uterine diagnosis and for singling out of the heterozygotes are still in the experimental stage and cannot yet be put to practical use. The BM test on meconium is, among the numerous neonatal screening, no doubt the most widely used because of its simplicity and low cost. However, our personal experience has confirmed the high incidence of false negative (60%) and of false positive responses (0.8 - 0.9%). This has brought about a reconsideration upon the usefulness of neonatal screenings and this goes for the most recent method based on the dosage of blood trypsin levels. Because of the many difficulties imposed by the neonatal screening, there is a trend towards alternative diagnostic route: the clinical diagnosis. One of the most important objective symptoms even if it may seem trivial, is the reduced ponderal growth: in our personal experience, 51% of patients when diagnosed presented with weight below 10th percentile. One of the most frequent clinical pictures in that of a severe obstructive pulmonary disease of the infant. The high incidence of CF (1 in 1,250 live births) and the high mortality rate in the first year of life (50% of patients die during their first year) indicate that CF weighs heavily on the infantile mortality due to lung disease considered globally. This holds true above all for the Emilia-Romagna region, where the infantile mortality due to lung disease has been drastically reduced. One of the most recently discovered clinical manifestations, more frequent in hot climates, is the metabolic alkalosis. There is then a long series of minor clinical signs which should make one suspect a CF: a few of these are prolapse of the rectum, nasal polyposis, the equivalent of meconium ileus, haemorrhagic symptoms due to hypoprothrombinemia etc. An instrumental confirmation, a sweat test carried out with the quantitative method according to Gibson and Cooke, must always follow each clinical suspect. Unfortunately, alternative methods (such as the Orion C1 electrode or the Medtherm conductivity method) which have very high margins of error are still too widely used, in Italy as well, and should be completely abandoned.
The aim of this research was to evaluate the response to aerosol antibiotic therapy in Cystic Fibrosis (CF) patients, who because of severe lung disease, were obligated to frequent hospitalizations to undergo intravenous antibiotic therapy. Ten patients, aged 2 to 20 years were submitted to 4 months cycles of aerosol antibiotic therapy for a total of 18 cycles. The daily treatment consisted of carbenicillin 1 g b.d. and gentamicin 80 mgs b.d. At the end of treatment there was a statistically significant improvement of the modified Huang score and of single clinical parameters such as body growth, apetite, physical activity, clinical thoracic evaluation, appearance of sputum. Almost all of the radiographic items remained unchanged: in only 4 cases there was an improvement of the atelectasis-broncopneumonia type lesions. Regarding lung function, there was a statistically significant increase of maximum midexpiratory flow rate (MMEF) from 40% predicted before treatment to 50% predicted after. The reduction of residual volume (RV) from 270% predicted before 170% predicted after treatment was quantitatively more important. Furthermore, the treatment brought about a drastic reduction in number of hospitalizations: from an average of 1,7 hospitalizations/year before to an average of 0,3 hospitalizations/year during treatment. The increased number of isolations of isolations of candida albicans is the only report which favors possible adverse effects, in particular the possibility that this type of treatment favors lung mycosis.
We report the prevalence of colonization of Group B Streptococci in a given population referred to a limited area in the north-west of Italy. 23.312 pregnant women were tested. Group B Streptococci have been isolated from genital cultures in 0.18-13.2% (mean 8.18). The prevalence of Group B streptococcal colonization from ear, throat and ocular cultures of newborn infants from colonized mothers was 11.55%. Incidence of infection in neonates has varied from 0 to 2.33% (1.5 per 1000 live births).
The individuation of a 5:1 ratio for the posology of beta 2-agonist drugs administered respectively by nebulizer or as a spray plus a spacer, allows the use of these drugs by the latter way also during an acute attack of bronchospasm. Other qualifying aspects of beta 2-agonist are the possibility of increasing the dose up to a continuous administration in case of a severe attack of bronchoconstriction and the demonstrated clinical efficacy of these drugs during the first year of life. The question of the correct dose to administer according to the age of the patient appears to be rather complex: in fact if on the one hand during the first months of life the low tidal volume (VT) can reduce the quantity of drug inhaled, on the other the low pulmonary volumes (FRC) of the first years of life determine a lesser dilution of the inhaled drug and therefore a greater pulmonary concentrations. Among corticosteroids for inhalation, the ones with the fewer side effects should be chosen: these may appear although in a subclinical fashion at relatively low doses of about 400 micrograms/day of beclomethasone. The most frequent indication for an antibiotic treatment by inhalation is represented by chronic pulmonary infection caused by bacteria sensible only to parenteral antibiotics (for ex. Pseudomonas infection in cystic fibrosis). The extremely high cost of these treatments requires the use of devices with a very high efficiency, in other words capable of nebulizing very large percentages of drug into small particles (< 6 microns).(ABSTRACT TRUNCATED AT 250 WORDS)
The dimension of the particles delivered by a compressor-nebulizer system and therefore the ability to penetrate in the distal lung, varies according to different nebulizers. Moreover the aerosol is better in quality higher the flow furnished by the compressors is. The quantity of drug inhaled is greater as lower the residual amount of liquid left in the nebulizer is: the latter is less in glass nebulizers than in plastic nebulizers. The ultrasonic inhaler does not present any qualitative or quantitative advantages respect to the pneumatic inhaler. A very important point in the execution of an aerosol is oral respiration. The administration of the drug through a mouthpiece does not present substantial differences respect to the use of a face mask kept in a vertical position and adherent to the face. Metered-dose inhalers shorten the time of performance, but an active cooperation is needed; moreover the quantity of drug that resides in the oropharynx increases and consequently adverse effects, too. These two obstacles are overcome by the use of spacers which are chosen on the basis of the child's age. Aerosolic treatment has been simplified by the use of powders for inhalation, but we do not always obtain correct inhaling flows in children, especially when they are bronchoobstructed. Therefore compressor or ultrasonic aerosol is more useful in bronchoobstruction, while metered-dose inhalers with spacers are more useful in long-term treatment. Powder is usually used in children over 6-7 years of age and excludes the use of important drugs, such as cortisone, which may present relevant adverse effects.
Ferritin is an ubiquitous iron storage protein that plays a key role in determining the intracellular fate of iron. Therefore, ferritin synthesis is highly regulated by the iron status of the cell through post-transcriptional mechanisms that involve a specific high-affinity interaction between an iron-responsive element (IRE) in the 5' untranslated region of ferritin mRNA and a 98 kDa cytoplasmic protein, the iron-regulatory factor (IRF). The mechanisms that regulate the expression of the iron storage protein ferritin were investigated in erythroid (Friend erythroleukemia cell, FLC) and fibroblastic (L929 and B6) cell lines after exposure to various iron compounds. Both hemin (ferric protoporphyrin IX) and iron (as ferric ammonium citrate, FAC) were used as inducers of ferritin synthesis. Administration of hemin increases ferritin synthesis 8-12 fold both in erythroid and in non-erythroid cell lines, whereas FAC is a weak inducer of ferritin in FLC (only 5-fold). These results correlate with ferritin mRNA expression in FLC observed after hemin treatment compared to the effect exerted by FAC administration. This differential effect suggests that heme is the physiological compound able to stimulate ferritin synthesis in erythroid cell lines and that it plays an important physiological role in regulating gene expression in developing erythroid cells.
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Treatment of asthma, in particular long-term therapy, has continued to evolve both for the perfectioning of single classes of drugs and for a better addressed long-term treatment, although physicians have not disposed of new drugs for over 30 years. Only with regard to chromones expectations have been disappointing, as the new nedocromil showed substantially the same efficacy as the old chromoglycate. The recent availability, in paediatrics, of long-acting beta 2 agonists, especially salmeterol, represents a big advantage with regard to compliance in therapies which last months, while the most recent corticosteroid, available in Italy as a spray, fluticasone, would have very few side effects. Principally this is due to the scarce intestinal absorption which is nearly non-existent. An old drug, such as theophylline, has been rediscovered because of the recent evidence of an antiinflammatory action. This is confirmed by the good results obtained when it is used for very long periods instead of inhaled corticosteroids. The therapeutical schemes of asthma have been modified since asthma has been demonstrated to be characterized more by phlogosis of the bronchial mucosa which persists after an acute episode rather than by broncho-constriction. This necessarily requires long-term therapies with antiinflammatory drugs which must be stepwise. In fact, the absence of an ideal drug determines the use of the drug with the fewest side effects in the less severe forms, i.e. chromones although less active, and of inhaled corticosteroids at increasing doses up to steroids per os in the more severe forms. Classical protocols suggest the combination with a beta 2-agonist (when necessary up to 3-4 times per day) to use corticosteroids as little as possible. However, recently short beta 2 agonists are being substituted by long-acting preparation which must be regularly administrated in the morning and evening.
If we assume that the only function of a spacer is that to facilitate the esecution of a spray, its use is limited to small children who do not collaborate (below age 6-7 years). However, spacers seem to improve the effectiveness of drugs and reduce both directly and indirectly the side effects. The assess if these characteristics have a role in clinical practice, the response to 100 micrograms of salbutamol administered directly by Autohaler was compared to that obtained with the same dose administered with three different spacers, Aerochamber, Babyhaler, Volumatic. A series of 88 asthmatic subjects with a FEF 25-75 less than 70% of the predicted value was considered. Overall patients provided 118 responses to the bronchodilator: 17 using the Aerotec (Autohaler), 38 the Aerochamber, 33 the Babyhaler, 30 the Volumatic. The response was evaluated considering the parameters obtained by spirometry just before, 5 and 20 minutes after the inhalation of salbutamol. Heart rate was also measured at the same time points. Heart rate, but not spirometric parameter were increased by the use of the Autohaler, proving that the drug had been inhaled. All the spacers determined a significant increase in the parameters considered. No significant difference was detected among spacers, although the smallest (Aerochamber, Babyhaler) showed a trend to a better response, in particular before age 7 years. The complete ineffectiveness of direct inhalation and the excellent response to inhalation with spacers show the indispensability of the latter, independent of age. Although no substantial difference among spacers was detected, the trend to obtain a better response with smaller spacers inclines us to use them in particular between 4 and 7 years of age. The negative correlation between the increase in spirometric parameters and the age of the patient would allow to have doses aimed to age or to body weight.
The failure to eradicate group A beta-hemolytic streptococci from the pharynx is partly due to a low compliance, but above all, an alteration of the oropharyngeal microbiological flora: reduction of alpha-haemolytic streptococci which inhibit group A beta-hemolytic streptococci and increase of microorganisms such as Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis. These latter act indirectly destroying the beta-lactamic ring of penicillins. However, this obstacle is overcome by the use of antibiotics which do not contain beta-lactamic rings such as macrolides or associating amoxicillin with clavulanic acid or with new cephalosporins which are more resistant to beta lactamases. To restrict the diffusion of resistance to antibiotics, it is essential to limit their use diagnosing streptococcal tonsillopharyngitis more precisely, thanks to an improved use of micro-biological diagnostic tests and by a more extended use of tonsillectomy in recurrent tonsillitis (more than 6-7 in 1-2 years). Adenoiditis is closely related to the post nasal drip syndrome, to recurrent otitis media and to otitis media with effusion. All these situations could, therefore, represent an indication, although not well defined, for adenoidectomy. Nasopharyngeal obstruction due to adeno-tonsillar hypertrophy becomes critical during sleep when the hypotony of the upper airway muscles becomes additional to the anatomical obstruction. At this point the inspiratory effort required and the consequent decrease of intra airway pressure increase the pharyngeal obstruction suctioning the pharyngeal walls toward the median line. The resulting clinical picture is defined as sleep-disordered breathing (SDB) due to adenotonsillar hypertrophy (idiopathic), to be distinguished from SDB due to cranio-facial abnormalities or neuromuscular diseases. SDB includes both the more serious sleep apnea syndrome and the less severe upper airway respiratory resistance syndrome. A combination of symptoms and clinical data detectable both while awake or asleep, make the diagnosis simple. During sleep, both apnea and paradoxical inspiratory movements are highly specific while snoring is highly sensitive. To evaluate nasopharyngeal obstruction radiography and optic fibre endoscopy are both equally reliable. The gold standard test for non idiopathic SDB is the polysomnography, whereas for SDB, due to adenotonsillar hypertrophy, one is limited today to the recording during sleep of O2 saturation or of end tidal CO2. These investigations are, however, generally used up to 2 years of age, when the decision to carry out an adenoidectomy and especially a tonsillectomy is more difficult because of the greater risks which surgery involves at this age. The pharmacological therapy has a purely palliative function and is based on antibiotics, local vasoconstrictors, steroids and theophylline which acts more as an antiflogistic than as a breath stimulant. O2 therapy and nasal continuous positive airway pressure (CPAP) give better results, but are more difficult to carry out, in particular on a long term basis. Adenoidectomy especially if associated with tonsillectomy, leads to the resolution of the symptoms, but not always to a normalization of functional alterations (hypoxia and hypercapnia). For this reason, it is necessary to act on other factors which cause oedema of the nasopharyngeal mucosa contributing to the obstruction. In this area, the prevention of viral infections can be achieved by vaccination against influenza and by preventing the child from attending crowded day care centers. With regard to allergic inflammation, skin prick tests could be a first step in view of allergens avoidance measures. With regard to indoor air pollution, passive smoke must be stopped and the child kept out of the kitchen.