[Ethics in perinatology]. / Etica in perinatologia.

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.

[Revisiting allergy. 35 years after Ishizaka's discovery of IgE]. / Ripensare le allergie, 35 anni dopo gli Ishizaka.

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.

Asymptomatic persistent pulmonary infiltrates in an immunocompetent boy with cat-scratch disease.

We describe here an immunocompetent boy with fever, regional adenopathy, multifocal hepatosplenic granulomas, and high and increasing serum antibody titers for Bartonella henselae in whom diffuse bilateral reticulonodular pulmonary infiltrates developed in the absence of respiratory symptoms.

Tolerance and hematopoietic stem cell transplantation 50 years after Burnet's theory.

OBJECTIVE: In 1949, the original formulation of Burnet's theory on the mechanisms responsible for the capacity of the immune system to discriminate between foreign antigens (i.e., the "non-self") and the cells of its own body (i.e., the "self") was published. Since then, further refinements and reconsiderations of the basic concepts underlying the achievement of a state of tolerance toward a certain antigen have been reported. Here, we attempt to analyze critically new clinical and experimental strategies aimed at inducing alloantigen-specific unresponsiveness. DATA SOURCES: The data discussed in this review are drawn from articles and abstracts published in journals covered by the Science Citation Index and Medline. STATE OF THE ART: Induction of tolerance toward alloantigens still remains one of the most elusive goals of clinical immunology. Until now, nonspecific immunosuppressive drugs have been used to successfully perform both solid organ and hematopoietic stem cell transplantation. However, using this approach, patients given an allograft are exposed to the threat of infections, tumors, and other side effects. Moreover, in solid organ transplant recipients, permanent tolerance toward the graft's alloantigens is never achieved. Recently, considerable progress has been made in expanding our knowledge of transplant tolerance. The traditional model of central tolerance, derived from Burnet's concept, has been complemented by knowledge of mechanisms of peripheral tolerance. CONCLUSIONS: New experimental and therapeutic trials based on the blockade of costimulatory molecules, as well as on generation and infusion of either regulatory or nonimmunogenic cells, have been recently proposed for inducing alloantigen-specific tolerance.The achievements obtained in understanding the mechanisms of unresponsiveness toward non-self antigens are fundamental prerequisites for successful allogeneic transplants, and they could open a new exciting era of specific, immunosuppressive therapies.

Alternative therapies and the Di Bella affair in pediatrics. A questionnaire submitted to Italian pediatric oncologists and hematologists.

BACKGROUND AND OBJECTIVE: 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. DESIGN AND METHODS: 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. RESULTS: 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. INTERPRETATION AND CONCLUSIONS: 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.

Tolerance and auto-immunity: 50 years after Burnet.

UNLABELLED: Fifty years ago Sir F. Macfarlane Burnet published his first fundamental contribution to the theory of immune tolerance he perfected 10 years later. Since then an impressive amount of new information on the function of the immune system has been gathered. As any original meaningful theory, Burnet's hypothesis on the development of immune tolerance has undergone extensive modifications to take into account all these new findings. An improved understanding of the mechanisms of tolerance has led to new possibilities for the treatment of auto-immune diseases. CONCLUSION: All new information in the field of immune function is rooted in Burnet's contribution which set the stage for the development of modern immunology.

Aortic valve regurgitation as the presenting sign of Takayasu arteritis.

UNLABELLED: Takayasu arteritis is a rare chronic vasculitis primarily involving the aorta and its main branches. We report an adolescent girl with Takayasu arteritis who presented with an isolated aortic valve regurgitation as part of a systemic inflammatory process. This patient was initially misdiagnosed as having rheumatic heart disease and the correct diagnosis was made only 1 year later. CONCLUSION: Takayasu arteritis should be considered among the diagnostic possibilities in patients who present with an unexplained systemic inflammatory syndrome and a cardiac murmur.

Transplant of hematopoietic stem cells in childhood: where we are and where we are going.

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.

Transplant of bone marrow and cord blood hematopoietic stem cells in pediatric practice, revisited according to the fundamental principles of bioethics.

The two most widely used sources of hematopoietic stem cells for allogeneic transplants in pediatric practice are bone marrow (BM) and cord blood (CB). While bone marrow transplantation (BMT) is reaching its 30th year of application, human umbilical cord blood transplantation (HUCBT) is approaching its 10th. Although these procedures have basically the same purpose, a number of biological differences distinguish them. In particular, the intrinsically limited quantity of CB stem cells and their immunological naiveté confer peculiar characteristics to these hematopoietic progenitors. From a bioethical point of view, the problems which have repeatedly been raised when the BM donor is a child are well-known. Different but no less important ethical problems are raised when one considers HUCBT; in this regard the most important issues are the easier propensity of programming a CB donor in comparison with a BM donor (clearly due to the shorter time interval needed to collect the hematopoietic progenitors); the in utero HLA-typing; the implication of employing 'blood belonging to a neonate' for a third party; the need to perform a number of investigations both on the CB of the donor and on the mother and the implications that the discovery of disease may have for them, but also the need to establish banks for storing CB, with the accompanying administration and management problems. All these different aspects of UCBT will be discussed in the light of the four fundamental and traditional principles of bioethics, namely autonomy, nonmaleficence, beneficence and justice.

[Diathesis and predisposition. A molecular reappraisal of the mode of reacting]. / Diatesi e predisposizione. Una rivisitazione molecolare del modo di reagire.

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.

Recurrent chest pain as the presenting manifestation of spinal meningioma.

We report the case of a 9-year-old boy with a spinal cord meningioma whose only manifestations were recurrent episodes of chest pain lasting for 2 years. This case shows that spinal cord meningioma should be considered among the possible causative factors of chronic chest pain in childhood.