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Subjects with Down syndrome (DS) have a high mortality due to infections and a high risk of developing malignancies. These observations, together with the demonstration of a frequent occurrence of HBsAg carrier state and of autoantibodies, have prompted investigations of the immune function in DS. Thymic morphological and functional abnormalities have been demonstrated. Peripheral blood mononuclear cells of DS subjects have been shown to include a high number of T lymphocytes with low avidity for sheep erythrocytes and a very high percentage of cells with an NK phenotype. However, NK activity is low in DS. Production of some important cytokines, such as IL-2, is depressed, thus contributing to T-cell derangement. Abnormalities of the B-cell compartment were also demonstrated, with a tendency towards high IgG and low IgM serum levels. Controversial results have been obtained with regard to antigen-specific antibody response. Also phagocytes of DS subjects display some characteristic functional impairments, with low chemotactic ability and reduced production of oxygen radicals. Despite the clearly established and rather detailed evidence of immune derangements, therapeutic trials have been anecdotal and resulted in marginal effects. HBV vaccination is highly advisable in DS because of the high risk of becoming chronic HBV carriers once infected.

The efficacy and safety of Cefetamet pivoxil in the treatment of community-acquired pneumonia in children were assessed in an open, randomised, comparative multicentre study in which 260 children (in- and outpatients) with either bacterial pneumonia (n = 170) or bronchopneumonia (n = 90) were enrolled. Cefetamet pivoxil, an oral third generation Cephalosporin, was administered to 85 children at a dosage of 10 mg/kg twice daily, the recommended therapeutic dosage, and to 94 children at a dosage of 20 mg/kg twice daily. Cefaclor was administered to 81 children at a dosage of 10 mg/kg three times daily. The duration of treatment was 7 days. Assessments were performed on days 0, 3, 7 and 14 after initiation of treatment. Clinical signs and symptoms began to improve soon after the start of treatment, and continued to improve in all 3 treatment groups. The therapeutic outcome was considered successful in 80 of the 81 assessable patients receiving Cefetamet pivoxil 10 mg/kg twice daily (98.8%), in 79 of the 81 assessable patients receiving Cefetamet pivoxil 20 mg/kg twice daily (97.6%), and in 71 of the 75 assessable patients receiving Cefaclor 10 mg/kg three times daily (94.7%). The differences in outcome between the 3 groups were not statistically significant. Adverse events were of gastrointestinal origin (mainly diarrhoea, nausea, and/or vomiting), and occurred with similar frequencies in the groups treated with Cefetamet pivoxil 10 mg/kg twice daily and Cefaclor 10 mg/kg three times daily. Cefetamet pivoxil administered at the standard dosage of 10 mg/kg twice daily was effective and well tolerated in children with bacterial pneumonia or bronchopneumonia. The twice-daily Cefetamet pivoxil dose schedule compares favourably with the well-established Cefaclor 3-times-daily regimen and may result in improved compliance.

The perinatal phase coincides, at its onset (22nd-23rd week of gestation, according to common acknowledgment), with the possible beginning of a extrauterine life susceptible of protraction. The 1st, for some the 4th, week of neonatal life marks the conclusion of the perinatal phase. There are several reasons to burden this period, to which a complex World Health Organization (WHO) document for Europe was dedicated in November 2000, with ethical issues. The profound immaturity that characterizes these extremely low weight newborns, of an approximate weight of 500 g, influences the poor survival prognosis (especially for those born within the 24th week), as well as the limitations concerning quality of life, often severe. Neonates born earlier than the 23rd week are at extreme risk, and rouse critical considerations regarding the choice of a health care program. A close monitoring of pregnancies at risk of premature termination, and a careful program of medical care for these extremely pre-terms, progressively implemented in the last 10-15 years, have given consistent results, reported in surveys of recent publication. From an ethical point of view, the problem of limitations within or beyond which to stretch intensive care interventions in Neonatal Intensive Care Unit (NICU) is still crucial, being the orientation between rational and emotional a difficult issue. Guidelines or behaviour proposals, variable with time and manifold in different countries, are reported. Naturally, the communication of a severe diagnosis to parents of a newborn even if not preterm-born falls also under the ethical issues of the perinatal period.

Some food intolerance ascribable to the individual, namely to the way he reacts to food (in particular, to cheese), was described by Hippocrates (as early as 460-375 B.C.) Since the beginning of modern era, a fascinating literature reports respiratory distress retrospectively viewed as of allergic-asthmatic origin. In the early twenties of 20th century the existence of "reagins" was first signaled, while we have to wait over four decades for the demonstration that these "reagins" were antibodies of the IgE class. However, at the present time, we have reached deep insight into the issue of allergy physio-pathology: from the role of Th2 lymphocytes to that of cytokines selectively involved in the onset of allergic inflammatory reactions, with the future goal of treatments focused more on the physio-pathology of "allergic reactions" than on counteracting its effects.

Over the last 2-3 years in particular, the so-called Di Bella therapy (DBT) become the most famous of alternative treatments applied to pediatric oncology and hematology in Italy. Many Italian oncologists and hematologists had to cope with the problems that it introduced and the treatment also elicited heated reactions all over Europe. We attempted to evaluate the impact of this treatment on children with cancer.A questionnaire prepared with the aim of addressing the use of alternative therapies in pediatric hematology and oncology was circulated to the 48 centers (or divisions) belonging to AIEOP (Associazione Italiana di Oncoematologia Pediatrica) [Italian Pediatric Oncology and Hematology Association] and FONOP (Forza Operativa Nazionale di Oncologia Pediatrica) [National Pediatric Oncology Task Force]. The questionnaire consisted of 9 questions elaborated to give credit to the case-related and professional experiences of the colleagues we contacted.Forty-three centers replied to the questionnaire. Request to switch to DBT represented a considerable problem, involving the vast majority of centers participating into this study; however, case quantification varied greatly from center to center. One of the most significant aspects is that children switched to DBT, abandoning conventional therapies, were often relapsing or had had multiple relapses (from solid tumor or leukemia), but some children abandoned conventional therapies at an early stage and/or without fully exploiting the curative potential of these therapies.This study allowed us to obtain an evaluation of the impact of DBT in children with oncologic or hematologic disorders. It also highlights the importance of cultivating physician-parent dialogue and provides an opportunity for a few pedagogic thoughts on the attitude and opinions of pediatricians on this problem.

Over the past decade, relevant improvements and refinements have significantly changed the indications, technique and results obtained with allogeneic transplantation of hematopoietic stem cells (HSC) in childhood. In this review the most important innovations that have characterized the practice of HSC transplantation in childhood during this decade will be discussed. We will analyze the clinical and biological advantages or disadvantages which characterize most typically HSC transplantation procedure in terms of the source of these cells (bone marrow, peripheral blood, placental blood). A fundamental turning point in the history of allogeneic transplantation of HSC is represented by the use of placental blood, which was first employed in 1988. Autologous, peripheral blood progenitor cells are increasingly being used as a source of HSC following high-dose therapy for malignant disease, because of the ease of collection and the markedly faster kinetics of engraftment in comparison with bone marrow. In particular, over the past decade, due to the much faster recovery of all hematopoietic lineages in comparison with bone marrow and due to the short duration of antibiotic therapy and hospitalization, also in pediatric patients, auto-transfusion of circulating hematopoietic progenitors is rapidly replacing autologous bone marrow transplantation after high-dose chemotherapy for lymphomas and solid tumors. On the contrary, due to concerns in pediatric patients related to the use of hematopoietic growth factors in a healthy donor, allograft of peripheral blood progenitor cells is not routinely used. Since indications for allogeneic HSC transplantation that had already been well established in the recent past have been complemented by others and a relevant number of disorders are no longer considered to be eligible for allograft, the evolution in the indications for allogeneic transplant of HSC in childhood will be discussed. Likewise, biotechnological, social and organizational refinements which have allowed the greatest advances of allogeneic HSC transplantation in this decade will be analyzed, as well as some still open bioethical question regarding this procedure.

The identification of the causes of important infectious and hereditary diseases became scientifically clear in the last years of the nineteenth century and in the first years of the twentieth. Through many centuries, the lack of etiologic knowledge regarding diseases has extraordinarily enhanced the value of the concept of predisposition so that "diathesis" helped to "explain" many forms of morbidity. Several discoveries as to the real "causes" of diseases, however, led to a critical downgrading of its value. But in-depth knowledge regarding the proteins controlled by genes of the "major histocompatibility complex" (MHC, HLA) in man was followed, a few years later, by the demonstration of the fact that carriers of particular alleles are exposed to higher risks of contracting certain diseases than non-carriers of these molecules. A new key for interpretation-this time, a genetic and molecular one-was thus offered for the concept of "predisposition". Actually, man's HLA-associated molecular individuality induces and causes an extraordinarily personal way of reacting to various stimuli. An obvious consequence of this is not only that man, having become aware of his "molecular uniqueness" (which is significantly HLA-related), can view himself as a "biological Ego" but, most of all, that some of his predispositions towards becoming ill may be ascribed to some of his individual molecular characterizations. Thus, the onset and the course of many diseases would be viewed as the effect of a given "way of reacting". This could be recognized as the true essence of diathesis, 18 centuries after Galen.

In recent years the concept of biological individuality has found ample acknowledgement in transplantation medicine; yet over 60 years ago Garrod had already grasped its real meaning in terms of a chemical individuality which he in turn envisaged as an explanation for the ancient concept of diathesis. HLA molecules have been recognized as being particularly representative of biological individuality, and their discovery has been followed by the observation that for some diseases there are measurable risks of predisposition which are indeed linked to certain antigenic-molecular HLA conformations. The biological individuality of man is thus acquiring an increasingly well-defined molecular characterization in which ancient diathesis presents a new and effective key for its interpretation.

Forty years after Bruton's discovery, the spectrum of primary defects of immunoglobulins has been largely extended and characterized. An increasingly more accurate recognition of the basic pathogenetic mechanisms of disease has helped to design more effective drugs and therapeutic strategies for patients with both primary and secondary immune deficiencies. In recent years, major advances in molecular biology have allowed characterization of the genetic basis of many primary immunodeficiencies, resulting in more accurate genetic counseling and leading to the first successful application of genetic therapy to the treatment of a human disease.

Optimal allogeneic bone marrow transplantation (BMT) presupposes the use of a HLA-identical sibling as donor. Unfortunately, only about 30% of patients have an HLA-matched donor, so that the use of alternative donors has been increasingly used. We report an analysis of 13 children transplanted using an HLA-partially matched donor as source of haemopoietic stem cells. They suffered of ALL (3 pts), ANLL (1 pt), SAA (2 pts), Osteopetrosis (1 pt), Wiskott-Aldrich Syndrome (2 pts), Severe Combined Immunodeficiency Disease (2 pts) and Familial Haemophagocitic Lymphohistiocytosis (2 pts). Full engraftment was obtained in all 11 of the patients who survived longer than 14 days and, globally, a moderate incidence of acute GvHD (grade II-IV) was observed in the evaluable patients (3 out of 11 with a percentage of 27%); only a patient of the six survivors more than one hundred days after BMT had severe chronic GvHD (16.6%). Four pts (31%) are actually alive and well (mean follow-up 358 days) with a mean Karnofsky score of 95%. Our data suggest that BMT from HLA-partially matched donors could represent a possible alternative therapeutic strategy in children when a compatible donor is not available. This is especially due to the reduced severity of GvHD in childhood and because of T-cell depleted marrow transplants could obtain more satisfactory results when employed in typical pediatric non-malignant disorders (i.e. immunodeficiencies) rather than in leukemia.

Starting from the conceptual premises of Garrod, who as long ago as 1902 spoke of "chemical individuality", and of Burnet (1949), who recognized as self one's own molecular antigenic structures (as opposed to the antigenic "alien": the non-self), the discovery and understanding of HLA antigens and of their extraordinarily individual and differentiated polymorphisms have gained universal recognition. Transplant medicine has now dramatically stressed, within man's knowledge of himself, the characteristic of his "biological uniqueness". Today man, having become aware of being a biological antigenic-molecular individuality which is unique and different from that of all of his fellow men (except for monozygotic twins), can therefore easily consider himself a true "biological Ego".

Durch die elektronenmikroskopische Untersuchung von Lymphknotengewebe eines an einer Lymphknoten-Toxoplasmose erkrankten 24jahrigen Mannes wurde eine Revision der lichtmikroskopischen Befunde ermoglicht. Damit konnten die diagnostischen Moglichkeiten deutlich erweitert werden, wie eine vergleichende Auswertung demonstriert. In einem Lymphknoten wurde intraarteriell ein Granulozyt nachgewiesen, der ein Protozoon enthielt. Auf die weitreichenden Konsequenzen dieses Zufallsbefundes wird hingewiesen.

T cell subpopulations of lymphocytes from cord blood (CBL) of 24 newborns and from peripheral blood (a-PBL) of 24 healthy adult volunteers were assessed in T cell-enriched, T cell depleted and unseparated lymphocyte fractions by using OKT3, 4, 6, and 8 monoclonal antibodies. The results show that T cell-enriched CBL include adult numbers of OKT3+, OKT4+, OKT6+ and OKT8+ lymphocytes whereas the T cell-depleted fraction consists of a high percentage of OKT8+, OKT3-, non-E rosette-forming cells bearing a PNA receptor. The presence of the PNA receptor and the lack of the OKT3+ antigen strongly support the hypothesis that the subset of OKT8+ cells in cord blood includes immature T lymphocytes that may represent an intermediate stage between thymocytes and mature peripheral T cells.

Samples of unstimulated whole saliva from 15 healthy children with 0.5--6 mg/100 ml of secretory IgA and from 10 healthy adults with 4--18 mg/100 ml of secretory IgA were pooled and treated in vitro with dithiothreitol and alpha-mercaptopropionylglycine. The effect of these reducing drugs on the immunochemical properties of secretory IgA was evaluated. Dithiothreitol induced depolymerization of secretory IgA and splitting of the secretory piece from the IgA molecule; furthermore it strongly reduced the titer of secretory antibodies to Escherichia coli antigens. The drug alpha-mercaptopropionylglycine apparently did not affect either the polymeric structure of secretory IgA or the titer of secretory anti-E. coli antibodies; however it induced splitting of the secretory piece. On the whole it appers that drugs with reducing properties, currently employed for liquifying mucous secretions in clinical practice, should be carefully evaluated for possible depressive side-effects on local immunity.

Das Symposium wurde auf Veranlassung des Bundesministers fur Jugend, Familie und Gesundheit unter der Federfuhrung der hiesigen Abteilung Ernahrungsmedizin und Ernahrungsphysiologie mit dem Ziel durchgefuhrt Anforderungen fur diatetische Lebensmittel zur Behandlung von Aminosaurestoffwechselstorungen fur eine Anderung der Diat-Verordnung festzulegen.

Monocyte-depleted lymphocyte suspensions from the peripheral blood of 36 healthy newborns and 23 adults were compared as to percent of cells forming rosettes with sheep erythrocytes (T lymphocytes) and proliferative responses after in vitro culture with various doses of Phytohemagglutinin, Concanavalin A and Pokeweed mitogen. No significant difference was found between the proportions of T lymphocytes of newborns and adults. Mitogen responsiveness of the newborn lymphocytes showed dramatic between-subject variability completely unrelated to the proportion of T lymphocytes. It is suggested that during neonatal life there is massive variable recirculation of T lymphocytes subsets (and/or stages of maturation) characterized by differential degrees of responsiveness to the mitogens tested.

The high degree of polymorphism of the genes controlling the immune system makes immune reactivity of any being very individualized. Self non self recognition, rejection of non-self is the most clear and common expression of this individuality. Moreover antigen experience, chance and even psychological conditions may further affect the immune response characteristics so contributing to enhance the individuality of the "way of reacting" and, therefore, of susceptibility to immune-mediated diseases. In this perspective man can consider himself as a true biological ego.

Thirty children in remission, at least one year after completing chemotherapy for Acute Lymphoblastic Leukemia, were assessed using general psychological measures. The Wechsler Intelligence tests were administered to evaluate their intellectual function: no significant reduction was found in overall IQ score. Only four of the patients, who presented neurological complications during the treatment, performed at lower levels. The group as a whole functioned poorly on tasks involving speeded performances and long-term memory. The age at diagnosis, the duration of the illness, the cranial irradiation and/or intrathecal-chemotherapy did not show any negative effects on the intellectual performance. Psycho-social adaptation was satisfactory: our patients do not show neurotic or psychotic disorders, but only affective disturbances (insecurity, irritability, poor self-perception, instability and depression). Familial adaptation was disturbed in 60% of the children and difficulty in socializing with peers was present in 57% of cases: the latter, in our experience, is related to poor self perception, present in 75% of our patients. We have found a more inadequate psycho-social adaptation in children who have not received any communication of their illness. Psychologic support can be of value for the child and his family in adapting to their difficult situation and in promoting a normal personality development of the child.

From an etiological viewpoint, urinary tract infections — which are often, especially in the pediatric age, associated with or favored by morbid situations that constitute either an obstacle to the urinary flow or lesion of the kidney or of the same urinary tract — are prevalently due to Gram-negative bacteria, in particular to germs of the coliform group (E. coli in particular but also Aerobacter aerogenes and Klebsiella pneumoniae), of the Proteus group, particularly Proteus vulgaris and Proteus morganii, and to Pseudomonas aeruginosa. According to some authors (Hradec et al 1972), about two thirds of the urinary infections are due to Gram-negative germs, with a large prevalence of E. con, Proteus and Pseudomonas. According to Sanna (1975), who reported on more than 8,000 strains isolated from urinary infections, E. coli is in question in 17% of the cases, Proteus in 20%, and Pseudomonas pyocyanea in 13.5%.

No organism from the cradle lives germ-free or allergen-free. The modalities by which infections facilitate conditions of abnormal reactivity, in particular respiratory asthma and allergy to cow milk proteins, are examined. 216 asthmatic children and 50 infants with rotavirus enteritis have been considered. Infections, besides representing stimuli directly projected on the immune system, also constitute factors which more generally influence the way of reacting.

Peripheral blood lymphomononuclear cells (PBL) from 35 patients with Down's syndrome (DS, trisomy-21; 25 institutionalized and 10 non-institutionalized) were phenotypically characterized by means of various monoclonal antibodies. They included a high percentage of T lymphocytes with low avidity for sheep erythrocytes as well as an extremely high percentage of HNK-1+ cells and of lymphocytes reacting with the OKT8 and Leu 2a antibodies. The HNK-1+ cells of DS include four different subsets: (a) E+, OKT3+, OKT8-, Leu 2a-; (b) E+, OKT3+, OKT8+, Leu 2a+; (c) E-, OKT3-, OKT8-, Leu 2a- and (d) E-, OKT3-, OKT8+, Leu 2a+. Subsets (a) and (c) are also present in PBL from karyotypically normal controls while subsets (b) and (d) have a phenotype which has not been previously reported. These findings may be related to the triple expression by trisomic cells of the receptor for interferon, which is coded by a gene located on chromosome number 21. Alternatively, the high number of 'immature' NK cells of DS, possibly identical with pre-T lymphocytes, may originate from the congenital thymic derangement associated with trisomy 21.

In order to investigate the ability of growth hormone (GH) to modulate lymphoproliferation, peripheral blood mononuclear cells (PBMC) from healthy adults were stimulated with phytohaemagglutinin (PHA) in the presence of increasing concentrations of pituitary (Crescormon) and biosynthetic (Somatonorm and Genotropin) GH (from 0.425 x 10(3) to 501.5 x 10(3) ng/ml) as well as biosynthetic insulin (rhinsulin, Humulin 1 Eli Lilly: from 0.0012 to 20 U/ml). The results obtained show that low doses of GHs and insulin increase lymphoproliferation. In contrast, high concentrations of GHs (8.5 x 10(3) ng/ml) induce a progressive decrease of PHA-induced lymphoproliferation, while insulin does not. No differences in cell viability were observed with and without GHs. Comparable percentages of lymphocytes bearing interleukin-2 receptor (CD25) and comparable values of interleukin-2 (IL-2) pr oduction were found in all conditions tested. Nevertheless, when exogenous recombinant IL-2 (R IL-2) was added to PHA-induced PBMC cultures with high doses of GH, a reconstitution of lymphoproliferation was observed. Further experiments seem to exclude the presence of suppressor T lymphocyte induction by GH. The present results suggest that hypothesis that high concentrations of GH may interfere with the binding between IL-2 and its membrane receptor on activated lymphocytes.

Anti-streptolysin O (ASO) antibodies are an expression of the frequent encounters even during the first years of life with beta hemolytic Streptococci, they are easily measured by quantitative laboratory tests and so possess the characteristics of a screening test for impaired antibody production. We have assessed ASO titers in 1955 healthy subjects of different ages (range: 1 month to 97 years). The behaviour of ASO titer is extensively described in the text. The percentage of people with less than 10 TU titers is under 5% after the age of 5 years up to 15 years; from 15 to 60 years there are no subjects with undetectable ASO titer and after this age the percentage is still under 5%. It seems therefore advisable not to define a "normal" treshold when titrating these antibodies to avoid the risk of missing low antibody producers.

Detection of specific IgE by the radioallergosorbent test (RAST) which uses labelled antibody can be hampered by the presence of antibodies other than IgE but with the same specificity and may limit usefulness of the RAST for diagnosis of IgE-mediated milk allergy in infancy when high titres of cow's milk protein-specific IgG antibodies are known to be present. This can be avoided by using a system employing labelled antigen, such as the enzyme-linked immunosorbent assay (ELISA) described here, where IgE in the test serum is immunoadsorbed to anti-human IgE coated to microtitre plates. Biotinylated antigen, in this case cow's milk proteins, binds to specific IgE and the reaction is revealed colorimetrically by adding horseradish peroxidase (HRP)-avidin conjugate.