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Home mattresses of 24 asthmatic children with house dust mite allergy were sprayed with either benzyl-benzoate foam or placebo in a double blind fashion, 10 days before the children left the residential house for asthmatic children Istituto Pio XII (located in the Italian Alps in an environment free of mites) and went back to their own home for the Christmas and Easter holidays. A further group of 8 children, whose mattresses received no treatment, was kept as an absolute control. Two days after spraying, benzyl-benzoate or placebo were vacuumed from the mattresses. Acarex test was performed immediately before spraying and at the end of each holiday period of 20 and 10 days, respectively. Bronchial hyperreactivity as well as serum and nasal secretory specific IgE for Dermatophagoides pteronyssinus were assessed in all children immediately before leaving and within 48 hr after returning to the residential house. The results of the study show that sprayed benzyl-benzoate foam was no more effective than placebo in reducing the level of house dust mite recovered from patients' mattresses, or in reducing bronchial hyperreactivity and IgE concentration in serum and nasal secretions.

Variations of serum and nasal specific IgE to Dermatophagoides pteronyssinus (Der p) during alternate periods of antigen avoidance-exposure have been evaluated with an open design in a group of allergic children with asthma and rhinitis at the residential house Istituto Pio XII (Misurina, BL, Italy), at 1756 m, in the Italian Dolomites. A method based on direct incubation of allergen coupled substrate on the nasal mucosa has been employed to evaluate the levels of nasal IgE. Serum specific IgE decreased respectively from (median) 117-89.3 kU/l (P < 0.001) during an initial period of 3 months of allergen avoidance and from 88.2 to 78.4 kU/l (P < 0.0002) during a subsequent period of allergen avoidance. No significant increase in serum specific IgE was, in contrast, observed during two periods, 22 and 9 days, of antigen exposure, changing respectively from 89.3 to 88.2 and from 78.4 to 89.1 kU/l. In contrast, nasal IgE has been significantly influenced by the alternate periods of antigen exposure-avoidance, showing a decrease from 19.75 to 4.01 kU/l (P < 0.0001) after the initial period of avoidance, followed by an increase to 9.95 kU/l (P < 0.0001) after 22 days of exposure. A significant decrease to a value of 2.37 kU/l (P < 0.0001) was also observed during the subsequent period of avoidance, followed again by an increase to 7.87 kU/l (P < 0.002) after 9 days of exposure. The evaluation of the kinetics of changes in nasal specific IgE revealed a significant decrease (P < 0.01) as soon as antigen avoidance was implemented for 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

A cohort of 12 asthmatic children was followed over several months, during which they moved back and forth from an allergen-free to an allergen-rich environment at high and low altitude, respectively. The children were treated with non-steroidal anti-asthmatic drugs as clinically needed. Histamine PC20-FEV1 was unaltered during the study period, whereas serum levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) showed significant changes when the children were exposed to the offending allergens. The total IgE significantly increased during exposure. The serum levels of myeloperoxidase (MPO) as well as of chemotactic factors for both neutrophils and eosinophils were unaltered during allergen exposure. We conclude that the serum markers of eosinophil activity ECP and EPX are sensitive indices of allergen exposure in asthmatic atopic children.

Eosinophils interact with extracellular matrix proteins and endothelial cells through adhesion proteins belonging to the beta 1 and beta 2 subfamilies of integrins. Extending previous observations, we found that tumour necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor stimulated generation of superoxide anion by eosinophils plated on fibronectin-coated surfaces. As studies with adherent neutrophils indicated that TNF might act as activating leucocyte integrins to deliver signals involved in activation of cell functions, we investigated the effects of monoclonal antibodies (mAb) directed against VLA-4 (CD49d/CD29), LFA-1 (CD11a/CD18), CR3 (CD11b/CD18) or the common beta 2 subunit (CD18) on generation of eosinophil toxic oxygen molecules and spreading. We show that cross-linking of members of both the beta 1 and the beta 2 integrin subfamilies triggers eosinophil respiratory burst and spreading. Evidence for the selectivity of anti-integrin mAb effects is derived from the findings that isotype-matched mAb of other specificities (anti-class I MHC Ag, anti-beta 2-microglobulin, anti-CD4) did not trigger eosinophil functions. The findings presented in this paper suggest that integrin-dependent, eosinophil adhesion in sites of allergic reaction may be accompanied by release of toxic oxygen molecules involved in tissue damage.

Inhaled corticosteroids are effective for the treatment of asthma. Because of the appreciation of the importance of airway inflammation in the pathogenesis of the disease, these drugs are being used more frequently not only in severe but also in moderate asthma. Treatment rarely has to be stopped because of topical adverse effects since oropharyngeal candidiasis and dysphonia are uncommon in children. However, paediatricians need to remain alert for the possibility of systemic adverse effects. With sensitive techniques, dose-dependent adrenal suppression has been documented in children treated with inhaled steroids but generally this effect has no clinical relevance. Although suppression of short term growth velocity has been reported, long term studies have shown that when growth impairment occurs in a child with asthma it is more likely to reflect poor asthma control than the administration of inhaled corticosteroids. Calcium supplementation may be necessary in children with asthma treated with inhaled steroids since this treatment may cause reduction in osteocalcin, a marker of osteoblast activity and bone formation. Other systemic adverse effects have been reported in case reports. The use of a large spacer device has been shown to reduce the incidence of both topical and systemic adverse effects from inhaled steroids and their use should be encouraged. In any child with asthma who really needs inhaled steroids, the lowest dose possible should be prescribed; however, the mistake of prescribing doses too low to be therapeutically effective should be avoided.

In the present study the inhibition by nedocromil sodium of the specific receptor binding of FMLP was evaluated in human neutrophils (PMNs) using a FMLP-(3H) binding assay. The time course of the binding was markedly influenced by nedocromil sodium used at a concentration of 300 microM. No significant inhibition was obtained when the cells were treated with nedocromil sodium 3 microM or with sodium cromoglycate 300 microM. FMLP binding is essentially eliminated by the highest dose of nedocromil sodium. The biologic meaning of this effect in asthmatic patients should be further evaluated.

In the present study we evaluated the allergenicity of infant formulas using a guinea pig model. Seven groups of ten guinea pigs each maintained on a diet free of cow milk received either water or pasteurized cow milk (PCM) or a conventional cow milk infant formula (CMF) or whey hydrolysate formula (WHF) to drink. On day 37 all the animals were challenged by intravenous injection with 0.5 mL of supernatant of either PCM or WHF. The reactions to the challenge were expressed as none, mild, severe nonfatal, and fatal. A score ranging from 0 to 3 was assigned to each animal and considered in the statistical analysis; P values are expressed as comparisons to the negative water-fed control group. Animals fed WHF and challenged with WHF (group 1), showed 10% fatal reactions and 50% severe but not fatal reactions (P less than .05). When challenged with PCM (group 2), 40% showed a mild reaction. Cow milk formula-fed animals showed 10% fatal reactions and 70% severe reactions when challenged with WHF (group 3). The same challenge caused 40% severe reactions in animals fed PCM (group 4) (P greater than .05). Animals fed and challenged with PCM (group 5) showed 100% fatal reaction (P less than .01). Animals fed water showed no reaction when challenged with either WHF (group 6) or PCM (group 7). The results suggest that WHF has less anaphylactic sensitizing power than PCM and CMF.

Twenty-nine asthmatic children were studied to assess their ability to detect the severity of their bronchoconstriction. First (STEP 0): each child was asked if he "felt asthma," inviting him to give a self-estimated obstruction score (SEOS) from 0 (no asthma) to 3 (severe asthma) and a baseline FEV1 was recorded. Then (STEP 1): methacholine was administered to all except 9 children with an FEV1 less than 80% of predicted who received saline nebulization and a second SEOS was recorded. Finally: salbutamol aerosol was administered and a third SEOS and FEV1 were obtained (STEP 2). Spearman's correlation coefficients r between SEOS and FEV1 were for the overall population -0.602, -0.517, and -0.104 at STEP 0, STEP 1, and STEP 2, respectively. The r values reduction during the trial can be due either to a decrease of children's concentration during the study or to a real difficulty in recognizing repeated changes in airway status. Some children tend to underestimate their bronchospasm. For these patients an accurate assessment of the severity of the bronchoconstriction requires an objective measurement during acute changes in asthmatic children.

The purpose of the present study was to evaluate the anaphylactic sensitizing power of cow milk, soy milk, casein hydrolysate, and a new cow collagen soy protein hydrolysate (CCSPH) infant formula in a guinea pig model of anaphylactic sensitization. Various groups of animals were fed these formulas for 37 days following which they were challenged intravenously either with the sensitizing constituent or one of the infant formulations. The results of these studies indicate a high degree of sensitizing capability of cow milk formula (80% fatal and 20% nonfatal) with reactions in guinea pigs challenged with BLG and no reactions when challenged with casein hydrolysate. In animals sensitized to soy formula there were only nonfatal reactions in 30% when challenged with soy protein. Casein hydrolysate and CCSPH were shown to be nonsensitizing. The results of these studies support he use of derivative infant formulas for the prevention of cow's milk hypersensitivity in infants.

This work was undertaken to improve a separation method for preparation of large amounts of erythroid cells of different age with homogeneous and minimal contamination of myeloid cells. Our method was suitably employed in the study of the decay mechanism of glucose-6-phosphate dehydrogenase (G6PDH) during the erythroid cell maturation. Twenty fractions of erythroid cells at different advancing stages of maturation were prepared by fractionating, at unit gravity, bone marrow cells from anaemic rabbit. The specific activity of the G6PDH was assayed and plotted vs the fraction number and the typical sigmoid curve of the activity decay was drawn. The separated cells were then grouped in three sets of fractions following the three phases of the sigmoid curve and the fractions of each set were combined. From the cytochemical analysis of the three main fractions so obtained, we found a 25-30% myeloid cell contamination in the first fraction, while in the other two fractions the myeloid contamination was 10% or less. For this reason we performed a rapid separation of the first fraction on a discontinuous percoll gradient. By this method, the myeloid cell contamination of the first fraction was levelled down to the other two. The fractions, so obtained, (I, II and III in order of increasing cell maturation) showed a four fold decrease of glucose-6-phosphate dehydrogenase activity expressed both per cell number and on protein base. On the contrary the concentration of the total soluble proteins did not change significantly in the three fractions. The three purified cellular populations were used to provide information on the protein turnover of the erythroid cells during their development. We measured, in intact cells, the rate of synthesis and degradation of total proteins and then, in cell lysates, we determined the rate of degradation of G6PDH, purified from rabbit RBC and radiolabeled by reductive methylation with C14-formaldehyde. The rates of proteolysis obtained with total proteins and methyl-G6PDH clearly indicate that the proteolytic machinery of the erythroblasts reduces its activity during the cell maturation.

In this two-stage, double-blind study, we evaluated the effects of different dosages of oxatomide (1 and 2 mg/kg/day) on nasal provocation and skin reaction wheal induced by grass-pollen challenge. Children with a positive history of allergic rhinoconjunctivitis and positive responses to skin prick test and nasal provocation test to grass pollen were studied out of season. The results obtained with 1 mg/kg/day of oxatomide demonstrated no significant difference in wheal areas and nasal secretion induced by allergen challenge between treated and untreated patients. The administration of 2 mg/kg/day demonstrated a significant suppression in wheal reaction and nasal secretion induced by specific challenge.

Leukotrienes (LTs), in particular LTC4, LTD4, and LTE4, have been shown to be capable of participating in the induction of three related processes observed during the immediate reaction in bronchial asthma: edema formation, mucus secretion, and muscle contraction. Despite impressive evidence potentially implicating the LTs, the role of LTs in asthma is still unproved, and a positive answer to their critical actions in causing airflow obstruction will require studies with specific antagonists.

The results of skin prick tests (SPT), radioallergosorbent tests (RAST), and multiple chemiluminescent tests (DHS-CLA) to grass mix, parietaria, D. farinae, and D. pteronyssinus were evaluated in 43 allergic children. All CLA tests had valid positive and negative control threads. Chemiluminescent assays class 4 matched with RAST class 3 and/or 4 and CLA class 3 with RAST class 2. The D. farinae, D. pteronyssinus, and grass results obtained with CLA, RAST, and SPT were investigated by principal components analysis that showed a good association between different methods of measuring allergenicity. The results of the present study confirm that DHS-CLA is an effective "in vitro" method for the detection of IgE-allergen specific antibody.

In this double blind study we evaluated the effect of a 2 months long treatment with inhaled beclomethasone dipropionate (300 micrograms/day) on methacholine responses in asthmatic children, during a period of maximal allergen exposure. Baseline values of methacholine PC20-FEV1 were 0.66 +/- 0.22 mg/mL (mean +/- SEM) in 10 children treated with the active drug and 0.78 +/- 0.21 mg/mL in 10 children treated with placebo. After 1 month of treatment PC20-FEV1 was 1.91 +/- 0.64 and 0.80 +/- 0.33 mg/mL, respectively, in the groups treated with beclomethasone versus placebo. A statistically significant reduction in bronchial hyperreactivity (PC20-FEV1, 5.49 +/- 1.86 mg/mL) but no systemic side effects were observed after 2 months of treatment with beclomethasone dipropionate. This is compared with a PC20-FEV1 of 1.38 +/- 0.52 mg/mL in the placebo group. The results confirm the effect of inhaled corticosteroids in reducing bronchial hyperreactivity, even during a period of maximal allergen exposure.

A double-blind study was carried out in 20 asthmatic children in order to evaluate the therapeutic efficacy and safety of inhaled corticosteroid flunisolide. 0.5 mg of the drug was administered by a jet nebulizer twice daily for 2 months. Respiratory symptoms, pulmonary function values and methacholine PC20-FEV1 were evaluated, as also morning cortisol levels, plasma cortisol increase after ACTH test, and 24-h urinary cortisol excretion. The data obtained show the efficacy of the drug in reducing symptoms. No significant difference was observed in pulmonary function values and in bronchial reactivity results between the two groups. No effect of flunisolide was observed on hypothalamic-pituitary-adrenal function. This study confirms the efficacy and safety of flunisolide (0.5 mg b.i.d.) in the treatment of asthmatic children.

Inhaled albuterol (A) (salbutamol) alone and albuterol plus ipratropium bromide (IB) were administered to 12 asthmatic children. Following administration of A alone or in combination with IB, there was a significant increase in FEV1 and FEF. Significant statistical difference in favor of the association A plus IB was observed at 120 and 240 minutes for FEV1 and in the period 120, 180, and 240 minutes for FEF. The additive effect was present both in the large and small airways. The short-lived additive effect of A plus IB suggests the opportunity to increase the frequency of drug administration in patients with severe bronchial obstruction.

Biphasic (early and late) asthmatic responses to exercise occurred in seven of 43 children with reproducible exercise-induced asthma. As biphasic allergen-induced asthma is associated with a prolonged increase in nonspecific bronchial hyperreactivity, this effect was not sought in the 43 asthmatic children. There was no significant change in methacholine PD20 FEV1 before and after exercise challenge, either in children who had early, or early and late, exercise responses. Late reactions after allergen exposure are likely to be of considerable clinical significance in relation to the enhancement of bronchial responsiveness. It is reassuring that this is not the case for exercise challenge, as it would have major implications in relation to the recommendations that asthmatics should participate in normal activities and even in training programs. Furthermore, it suggests that there are differences between the pathophysiology of asthma induced by exercise and that produced by allergens.

Ten adult rabbits were divided into two groups: the control rabbits, which received subcutaneous injections of 0.9% NaCl in three days; the experimental animals which received 3 mg/Kg body weight of phenylhydrazine (PHZ) subcutaneously also in three days. On the 8th day from the initial treatment the control and experimental animals were sacrificed, blood was collected to determine hematological parameters and livers were cut into small pieces. Sections were prepared by pressing the pieces onto slides which were stained with the Giemsa stain. The hematocrit and the reticulocytosis of experimental animals were 25 + 3%, and 70 + 5% respectively. In the liver sections of the PHZ treated animals we found a very rich population of immature erythroblasts. In fact proerythroblasts and basophilic erythroblasts were 19%, polychromatic and orthochromatic erythroblasts were 22% and 13% respectively. On the contrary, these cells were absent in the control livers. The lymphocyte and lymphoblast population, on the other hand, was very rich in control animals with a value of 38.8% compared to 1.62% in the anemic animals. The results clearly indicate the hematopoietic function of the liver in the anemic animals although the low percentage of orthochromatic erythroblasts with respect to their precursors suggests the ineffectiveness of the process.

The glucose-6-phosphate dehydrogenase (G6PD) activity of erythroblasts, separated at different advancing stages of development, shows a marked decline of activity. A proteolytic mechanism, strictly controlled, is likely responsible of this decay, since a sufficient level of enzyme activity still remains in the circulating erythrocyte. In this report we suggest a model that could explain what triggers the mechanism of proteolytic degradation. HPLC analysis of the nucleotide content of erythroblasts and reticulocytes, showed a marked decline of adenine and pyridine nucleotides and of their catabolic products during the cell development. From thermostability tests, at fixed temperature, we have seen that ATP and NADP only, significantly protected the enzyme activity. In this light, we incubated 10 min at increasing temperatures, with and without ATP or NADP lysates of erythroblasts, separated at different stage of development and of reticulocytes. In the absence of nucleotides, we determined for all fractions a T degree break at 42 degrees C. In the presence of NADP all fractions were stabilized with no break point in the range 37-50 degrees C. On the contrary, the presence of ATP caused a progressive shift of the T degrees C break from the most immature erythroblasts (T degree break at 46 degrees C) to the reticulocytes (T degree break at 42 degrees C). Since ATP did not show any protective effect on the reticulocyte enzyme, we hypothesize the presence in these cells of a structurally modified G6PD. Furthermore, these data support our belief that the marked decline of ATP during cellular development, may represent the element responsible for the enzyme modification.

Male rabbits were made anemic by subcutaneous injections of 3 mg/Kg body weight of phenylhydrazine (PHZ) for the duration of three days. Blood samples were collected prior to the experiment, on the 2nd and 5th day from the end of the treatment. Hematocrit, reticulocyte count, MCV, osmotic resistance, RBC volume distribution curve and morphological analysis were performed on each sample in order to obtain a picture of the progressive changes of the parameters following the PHZ administration. Hematocrit values changed from 49 to 27%, whereas the reticulocytosis increased from 0.6 to 73%. A significant elevation of MCV was detected and the cell volume distribution curve, which presented the typical bell-shape profile in the normal animals became bimodal on the 5th day. The osmotic resistance of RBC of anemic animals, showed a marked deviation from the normal pattern. In fact initial haemolysis started at 0.75-0.70% NaCl concentration in the 5th day samples, while it was between 0.55-0.50% before the PHZ treatment. Finally, morphological analysis revealed a progressive increase of RBC with Heinz bodies, of macro-megalocytes and of immature erythroblasts thus indicating that the cell population, produced during recovery from PHZ induced anemia, is widely heterogeneous.

The present study was performed to evaluate the effect(s) of theophylline on BCG-induced pulmonary inflammatory responses in an experimental rat model system. Five groups of six animals each received the following: group 1: theophylline-treated, BCG-challenged, and sacrificed three days later; group 2: saline-treated, BCG-challenged, and sacrificed three days later; group 3: theophylline-treated, BCG-challenged, and sacrificed five days later; group 4: saline-treated, BCG-challenged, and sacrificed five days later; and group 5: no treatment and no BCG-challenge ("absolute controls"). Quantitative recovery of bronchoalveolar lavage (BAL) cells was performed and compared with histopathologic changes in lung specimens from each animal in all five groups. No significant differences in quantitative BAL cellular recovery were observed in theophylline-treated animals from saline-treated controls. There was a significant reduction in BAL cell number in saline-treated animals sacrificed five days after BCG-challenge (group 4) from that seen in saline-treated animals sacrificed three days after BCG-challenge (group 2). The most striking finding, however, was a marked diminution in granuloma formation induced by theophylline five days after BCG challenge (group 3). These findings suggest an antiinflammatory effect of theophylline.

A double-blind crossover study was performed to evaluate the bronchodilating effect of different single doses of procaterol (less than 0.5 micrograms/kg, 1.5 micrograms/kg, and placebo) orally administered. Sixteen asthmatic children, age 6-12 years, participated in the trial. Pulmonary function, heart rate, blood pressure, and tremor were evaluated at 30, 60, 90, and 120 min and then hourly for 8 hours after administration. All three doses were therapeutically effective. The 1.5 micrograms/kg dose produced a more sustained bronchodilatation effect, but was also associated with an increase in the incidence of tremors. The 0.5 micrograms/kg dosage may, however, be a good starting dose because it assures a reasonable risk/benefit ratio.

The glucose 6 phosphate dehydrogenase (G6PD) activity of erythroblasts, separated at different advancing stages of development by the velocity sedimentation technique at unit gravity, shows a characteristic sigmoidal curve. The G6PD activity is high and constant in the dividing compartment, steeply declines between the polychromatic and the orthochromatic stage, and returns almost constant during the development from the orthochromatic to the reticulocyte stage. This report focuses on the possibility to use the G6PD activity curve to indicate a loss of resolution in the fractionation process. For this purpose two parameters of the graph were used: (h) which represents the distance between the two constant phases of the curve and (s) the slope of the decreasing part of the graph. In this view we have fractionated on a 400 ml linear gradient of sucrose (1%-2% in PBS), increasing amounts of bone marrow cells from anaemic rabbit. Suspensions of 100, 200, 350 and 700 millions of cells (25 ml in PBS) were separated in different experiments and the obtained G6PD activity curves were compared. We have seen that the two parameters h and s remained constant up to 200 millions of cells, while they declined markedly when the number of cells loaded on the gradient increased to 350 and 700 millions. The separated cells were grouped into three sets of fractions: fraction I with cells belonging to the high and constant phase of the graph, fraction II to the decreasing phase and fraction III to the low and constant activity phase.(ABSTRACT TRUNCATED AT 250 WORDS)

The splenic hemopoiesis of rabbits, made anemic with acetylphenylhydrazine, and of control animals was investigated. Pieces of spleen of both groups were fixed in formalin and embedded in paraffin. Paraffin sections, cut 5-7 microns in thickness, were stained with hematoxylin-eosin, Giemsa, Perls' method for tissue iron (hemosiderin), and Perls-Chayen's method for iron stored in the hemoglobin. The erythroid line in the anemic rabbits, showed a marked increase of proerythroblasts and basophilic erythroblasts, while the poli and orthochromatic erythroblasts were less than their precursors. In contrast these cells were more than their precursors in control animals. There was no notable quantitative difference in the mature elements of this line in the anemic animals and in the controls. Megaloblasts and macroblasts were frequently observed in anemic spleens but they were practically absent in the controls. Regarding to other cell lineages, we noted in the anemic spleens many macrophages containing Perls and Perls-Chayen positive material and some megakaryocytes. Our results indicate that the APH-induced anemia stimulate the erythropoietic activity of the spleen in the rabbit, but the reversion of the amplification phase of the differentiation steps reveals that the erythropoietic process is ineffective. The presence of megalo- and macroblasts provide morphological evidence of dyserythropoiesis and the megakaryocytes suggest that under the anemia condition also the platelet regenerating process is stimulated.

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.

We undertook a four year study of 128 thalassaemic patients who had undergone several transfusions, to determine the incidence of hepatitis B virus markers and the activities of transaminases in their sera each month. The results showed that the possibility of these patients contracting hepatitis B virus infection is still high, although on only one occasion was a transient antigenaemia found, indicating low viral replication. Furthermore, the probability of contact with hepatitis B virus increases with the number of transfusions and, therefore, with age. About 25% of these patients were positive for hepatitis B markers and 80% for other hepatitis markers including the case of cytomegalovirus hepatitis.

The hematological parameters of young (2-month-old) and old (2-year-old) mice were compared. No differences could be detected with the exception of an increased percentage of reticulocytes in the old animals suggesting that anemia in senescent mice does not occur. Red blood cell mean half-life in old mice was 8 +/- 0.8 days compared to 12 +/- 1 days in young mice. This reduced survival of red blood cell is not due to a different rate of cell phagocytosis in the reticulohistiocytic system of young and old animals since erythrocytes from young mice have the same mean half-life when injected both in young and old animals and vice versa. Thus, the old mice have a reduced red cell life-span but the same hematocrit of the young, suggesting that old animals possess a chronologically younger population of erythrocytes than do young animals. This has been confirmed by measuring the specific activities of some red blood cell age-dependent enzymes (hexokinase, glucose-6-phosphate dehydrogenase, pyruvate kinase) that were found to be higher in the older animals, and by the separation of erythrocytes into different density (age) groups by Percoll/albumin density gradient centrifugation. However, the erythrocytes osmotic fragility, and the cellular contents of adenine and pyridine nucleotides, as well as the content of 2,3-diphosphoglycerate and reduced glutathione, show that circulating erythrocytes in old animals constitute an heterogeneous cell population whose properties cannot be explained on the basis of a chronologically younger erythrocyte population. Furthermore, evaluation of cell components in hemopoietic tissues have shown an increased porportion of erythroid precursor cells in old animals confirming that old mice compensate for reduced red cell survival with an increased erythropoiesis.

Between 1 July 1984 and 30 June 1986 all children treated for acute hematologic malignancy at our center were randomized to receive continuous (group A) or intermittent (3 days/week, group B) prophylaxis with trimethoprim-sulfamethoxazole (5-25 mg/kg/day/p.o.) against interstitial pneumonia with the aim of investigating if an intermittent regimen is as effective as and less toxic than a continuous regimen. The number of severe infections (group A, 17; group B, 21) and side-effects (group A, 30; group B, 34) was similar in the two groups, and compliance was also similar. We conclude therefore that neither regimen offers advantages over the other and the decision which to use should be based on cost (where regimen B has the advantage) and the children's and parents' preferences and compliance.

The maintenance of physiological levels of haemoglobin is beneficial in the management of patients with thalassaemia major since it leads to better tissue oxygenation, reduction of blood volume, and reduced intestinal absorption of iron. We have studied 11 patients with thalassaemia major while treating them for 4-12 months with a standard transfusion regimen (mean pre-transfusion Hb 10.2 g/dl) and then for a second period of 7-18 months with a supertransfusion regimen (mean pre-transfusion Hb 12.3 g/dl). Blood consumption was 16.71 +/- 2.0 ml/kg/month in the first period; it rose to 20.30 +/- 3.5 ml/kg/month in the first 5 months of the second period, and then returned to the values of the first period (16.53 +/0 2.0 ml/kg/month). There were no significant differences in blood consumption between the two transfusion regimens, after the 5-month equilibration period.

The incidence of skin test and RAST positivity for Dermatophagoides farinae and storage mites (Glycyphagus privatus, Lepidoglyphus destructor, Tyrophagus putrescentiae, Acarus siro, and Gohieria fusca) have been evaluated in children with bronchial asthma and positive prick test to Dermatophagoides pteronyssinus. The storage mite with highest incidence of skin and RAST positivity was Gohieria fusca, which caused a positive response in more than 50% of the children evaluated. This antigen appears to possess allergenic determinants not present in Dermatophagoides pteronyssinus. The sensitivity to this antigen might be considered in house dust mite-allergic children who do not improve after specific immunotherapy with Dermatophagoides pteronyssinus extracts.

The prognosis of leukemia in children has changed remarkably in the last 20 years. Today more than 50% of children with Acute Lymphoblastic Leukemia (ALL) and about 30% of children with Acute non Lymphoblastic Leukemia (ANLL) can be cured with chemotherapy. The German Group BFM has obtained a significant improvement of results, both in ALL and ANLL using multidrug intensive treatment schedules. In Italy, thanks to the Italian Pediatrics Association of Hematology and Oncology (AIEOP), results have been improved in the last 10 years; very recently, new protocols with the BFM strategy have been started. Allogenic matched bone marrow transplantation (BMT) is indicated in children with ALL in 2nd complete remission (CR) following a relapse during or shortly after discontinuing treatment and in patients with Chronic Myeloid Leukemia. Chemotherapy results remain very poor in these patients. Allogenic BMT in usually performed also in children with ANLL in 1st CR. Autologous BMT, and allogenic BMT mismatched or from unrelated donors are being used with promising results when matched donors are not available. Most children cured of leukemia can enjoy a normal quality of life. However long term studies are still needed to determine the incidence of late effects, and to evaluate the psychosocial impact of the disease. In this context is becoming more and more important the role of the family doctor.

Airway inflammation is consistently present in patients with severe asthma. The combination of inhaled steroids and bronchodilators may be useful both for treating symptoms and improving the underlying inflammatory condition. We have compared the effect of beclomethasone dipropionate (BDP) combined with salbutamol (S), BDP alone, and placebo, on the severity of bronchial responsiveness in 30 children with allergic asthma during the period of specific allergen exposure. In children treated with BDP alone, PC20-FEV1 methacholine was 0.66 +/- 0.54 at the beginning and 1.91 +/- 2.11 at the end of the study period (p greater than 0.05). In children treated with BDP + S PC20, methacholine was 1.21 +/- 1.43 at the beginning and 4.22 +/- 3.88 at the end of the study (p less than 0.05). The group of children treated with placebo had a PC20-FEV1 methacholine of 0.79 +/- 0.61 at the beginning of the study and 0.80 +/- 0.46 at the end of the study. The results of the present study show that maintenance treatment with inhaled beclomethasone combined with salbutamol may lead to greater improvement in bronchial hyperreactivity than treatment with inhaled beclomethasone dipropionate alone.

A study of hexokinase isozymic pattern and age dependence of the enzyme was carried out on erythrocytes of 4 patients with adenocarcinoma of the gastrointestinal tract. On the basis of our results, we think that the increase in hexokinase activity previously reported and the increase in both subtypes (Ia and Ib) of the enzyme herein described are not due to a mean younger red cell population caused by secondary anemia, which is frequently present in cancer patients.