bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of proximal 1p36 deletions using array‐CGH: a possible new syndrome
Authors: Kang S‐HL , Scheffer A , Ou Z , Li J , Scaglia F , Belmont J , Lalani SR , Roeder E , Enciso V , Braddock S , Buchholz J , Vacha S , Chinault AC , Cheung SW , Bacino CA
Published: September 2007

Monosomy 1p36 is the most common terminal deletion syndrome with an estimated occurrence of 1:5000 live births. Typically, the deletions span <10 Mb of 1pter‐1p36.23 and result in mental retardation, developmental delay, sensorineural hearing loss, seizures, cardiomyopathy and cardiovascular malformations, and distinct facies including large anterior fontanel, deep‐set eyes, straight eyebrows, flat nasal bridge, asymmetric ears, and pointed chin. We report five patients with ‘atypical’ proximal interstitial deletions from 1p36.23‐1p36.11 using array‐comparative genomic hybridization. Four patients carry large overlapping deletions of ∼9.38–14.69 Mb in size, and one patient carries a small 2.97 Mb deletion. Interestingly, these patients manifest many clinical characteristics that are different from those seen in ‘classical’ monosomy 1p36 syndrome. The clinical presentation in our patients included: pre‐ and post‐natal growth deficiency (mostly post‐natal), feeding difficulties, seizures, developmental delay, cardiovascular malformations, microcephaly, limb anomalies, and dysmorphic features including frontal and parietal bossing, abnormally shaped and posteriorly rotated ears, hypertelorism, arched eyebrows, and prominent and broad nose. Most children also displayed hirsutism. Based on the analysis of the clinical and molecular data from our patients and those reported in the literature, we suggest that this chromosomal abnormality may constitute yet another deletion syndrome distinct from the classical distal 1p36 deletion syndrome.
Formalin‐fixed paraffin‐embedded clinical tissues show spurious copy number changes in array‐CGH profiles
Authors: Mc Sherry EA , Mc Goldrick A , Kay EW , Hopkins AM , Gallagher WM , Dervan PA
Published: September 2007

Formalin‐fixed paraffin‐embedded (FFPE) archival clinical specimens are invaluable in discovery of prognostic and therapeutic targets for diseases such as cancer. However, the suitability of FFPE‐derived genetic material for array‐based comparative genomic hybridization (array‐CGH) studies is underexplored. In this study, genetic profiles of matched FFPE and fresh‐frozen specimens were examined to investigate DNA integrity differences between these sample types and determine the impact this may have on genetic profiles. Genomic DNA was extracted from three patient‐matched FFPE and fresh‐frozen clinical tissue samples. T47D breast cancer control cells were also grown in culture and processed to yield a fresh T47D sample, a fresh‐frozen T47D sample and a FFPE T47D sample. DNA was extracted from all the samples; array‐CGH conducted and genetic profiles of matched samples were then compared. A loss of high molecular weight DNA was observed in the FFPE clinical tissues and FFPE T47D samples. A dramatic increase in absolute number of genetic alterations was observed in all FFPE tissues relative to matched fresh‐frozen counterparts. In future, alternative fixation and tissue‐processing procedures, and/or new DNA extraction and CGH profiling protocols, may be implemented, enabling identification of changes involved in disease progression using stored clinical specimens.
The immunoinformatics of cancer immunotherapy
Authors: DeLuca D. S. , Blasczyk R.
Published: September 2007

We review here the developments in the field of immunoinformatics and their present and potential applications to the immunotherapeutic treatment of cancer. Antigen presentation plays a central role in the immune response, and as a result in immunotherapeutic methods such as adoptive T‐cell transfer and antitumor vaccination. We therefore extensively review the current technologies of antigen presentation prediction, including the next generation predictors, which combine proteasomal processing, transporter associated with antigen processing and major histocompatibility complex (MHC)‐binding prediction. Minor histocompatibility antigens are also relevant targets for immunotherapy, and we review the current systems available, SNEP and SiPep. Here, antigen presentation plays a key role, but additional types of data are also incorporated, such as single nucleotide polymorphism data and tissue/cell‐type expression data. Current systems are not capable of handling the concept of immunodominance, which is critical to immunotherapy, but efforts have been made to model general aspects of the immune system. Although tough challenges lie ahead, when measuring the field of immunoinformatics on its contributions thus far, one can expect fruitful developments in the future.
The nature of diversity of HLA‐DRB1 exon 3
Authors: Horn P. A. , Albis‐Camps M. , Verboom M. , Bunce M. , Yousaf K. , Williams S. , Blasczyk R.
Published: September 2007

Exon 3 of DRB1 is known to be polymorphic, but thought to be conserved within allelic groups. This implies that exon 3 polymorphisms would not need to be considered in evolutionary studies or clinical settings when assessing immunogenicity of allelic mismatches in stem cell transplantation. To further assess this, we determined the sequences of DRB1 exon 3 by hemizygote amplification and direct sequencing on 55 selected DNA samples containing 42 DRB1 alleles for which no exon 3 sequence data were previously available. The data confirmed the high degree of overall sequence conservation. The DRB4‐ and DRB5‐associated alleles were completely conserved within their DRB1 groups. However, it could be shown that exon 3 is more diverse than previously expected. Multiple allelic differences within each group of DRB3‐associated DRB1 alleles were found, without identifying unique group‐related sequence motifs differentiating between these groups. For DRB1*1402 and DRB1*1406, it could be shown that they originated from DRB1*0302. In several samples previously typed as DRB1*1401, a novel DRB1 allele was identified: DRB1*1454. Thus, from a clinical viewpoint, the availability of exon 3 sequence information may be useful for optimizing typing as well as matching strategies. Additionally, it will allow for more detailed evolutionary studies, further elucidating the origin of alleles and the mechanisms driving sequence diversification.
Bioinformatic integration of biomechanics makes HLA sequencing universally applicable
Authors: Verboom M. , Hallensleben M. , Horn P. A. , Blasczyk R.
Published: September 2007

Sequencing provides the most reliable and accurate information of the sequence of a gene and is therefore of particular interest for fully characterizing the genetic complexity and allelic diversity of human leukocyte antigens (HLA) genes. This complexity makes sequencing the method of choice for HLA low‐ and high‐resolution typing. However, sequencing is considered a complex process, which requires the management of an overwhelming amount of data. However, only sequencing can be used as a sole typing technique without the need of supplementation by other typing techniques; it offers additional advantages by providing results in electronic formats and by being fully automatable. This makes sequencing the best candidate for bioinformatic and biomechanic integration to maintain the benefits and discard the drawbacks. We have, therefore, developed robotic platforms and a bioinformatic tool allowing complete documentation, interpretation and processing of all amplification and sequencing steps as well as the full integration of all instruments involved. It was shown that this integrative approach allows sequencing to run fully automated for low‐ and high‐resolution typing on each throughput level desired. This integration of robotics and software secures the traceability of each specimen at each step of the process and minimizes the risk of contamination and sample mix‐up.
New insights into pediatric rhinosinusitis
Authors: Principi N. , Esposito S.
Published: September 2007

Rhinosinusitis is a common children’s disease. Most cases are acute, follow an episode of common cold, and are the consequence of a superimposed bacterial infection. If mild, they are characterized by the persistence of signs and symptoms of upper respiratory tract disease for more than 10 days; if severe, they involve fever and a purulent nasal discharge, and can cause a substantial decline in general health. Recurrent acute or chronic cases are usually diagnosed in children with predisposing factors, such as recurrent respiratory tract infections, allergic rhinitis, cystic fibrosis, immunodeficiency, ciliary dyskinesia, anatomic abnormalities or reflux. Therapy is based on antibiotics, administered orally in mild, and intravenously in severe cases. On the basis of recently highlighted antibiotic resistances and the possibility of spontaneous resolution, experts agree in considering amoxicillin the drug of choice for mild cases, and an antibiotic capable of overcoming all possible resistance for severe cases.
Inflammation of paranasal sinuses: the clinical pattern is age‐dependent
Authors: Marseglia G. L. , Castellazzi A. M. , Licari A. , Marseglia A. , Leone M. , Pagella F. , Ciprandi G. , Klersy C.
Published: September 2007

Acute rhinosinusitis (ARS) represents a common disorder, associated with consistent morbidity as well as with a large prescription of antibiotics. ARS has a significant impact on clinical practice; it usually presents with respiratory complaints persisting longer than 10 days and showing no signs of improvement. Throughout the evaluation of 256 pediatric patients (152 males and 135 females, aged between 2 and 15 yr), with ARS confirmed by nasal endoscopy, we have been able to provide evidence that age has a significant influence on clinical patterns in children with ARS.
The child with recurrent respiratory infections: normal or not?
Authors: De Martino M. , Ballotti S.
Published: September 2007

Respiratory infections (RI) are one of the major complaints in children and adolescents, and represent a demanding challenge for the pediatrician. It has been estimated that at least 6% of Italian children younger than 6 yr of age present recurrent respiratory infections (RRI). Children with RRI are not affected by severe alterations of the immune system. RRI represent essentially the consequence of an increased exposure to infectious agents during the first years of life, when immune functions are still largely immature. Several social and environmental factors, such as day‐care attendance, family size, air pollution, parental smoking, and home dampness, represent important risk factors for airway diseases and may contribute in various degrees to determine the incidence of RRI. The main problem for the pediatrician is to discriminate normal children with high RI frequency related to an augmented exposure to environmental risk factors from children affected by other underlying pathological conditions (immunological or not), predisposing to infectious diseases. When RRI diagnosis has been formulated, removal of environmental risk factors (i.e. precocious day‐care attendance, smoking in the household) must first be suggested.
Chronic rhinosinusitis and allergy
Authors: Leo G. , Piacentini E. , Incorvaia C. , Consonni D. , Frati F.
Published: September 2007

The role of allergic sensitization in chronic sinusitis in childhood is currently unclear, as contrasting results were reported in the studies thus far available. In fact, some surveys found prevalence of atopy up to 60% in subjects with chronic sinusitis, while other failed to confirm any association between the two conditions. The data we obtained in a cross‐sectional study on a large population of children should help in better defining such issue. Among 2200 children referring for evaluation of chronic respiratory symptoms, subjects satisfying at least two of major criteria for the definition of chronic sinusitis were recruited, and underwent to allergen sensitization workup by skin prick test with common inhalant allergens and total IgE measurement. Patients were stratified according to age lower than 3 years (group 1), age between 3 and 6 years (group 2), and age above 6 years (group 3). In all, 351 children (217 boys, 134 girls, mean age 5.23 ± 2.11 years, range 1.5–15 years) were available for evaluation and formed three groups (27 in group 1, 261 in group 2 and 63 in group 3). Prevalence of both sensitization to at least one inhalant allergen by skin test and of high total IgE was 29.9%, with significant difference for the former across age groups, with a value of 7.4% in group 1, 31.4% in group 2 and 33.3% in group 3 (p = 0.028), but after adjusting for age, sinusitis and aeroallergen sensitization were not significantly correlated. The difference across groups for high total IgE did not reach statistical significance, with respective prevalence of 22.7%, 30.1% and 32.1%. It is possible to conclude that the prevalence of sensitization to aeroallergens in children with chronic sinusitis is comparable with that of the general paediatric population, as assessed in the Italian arm of the ISAAC study and this does not account for routine investigation for allergy in children with chronic sinusitis.
Chronic and recurrent cough, sinusitis and asthma. Much ado about nothing
Authors: Barbi E. , Longo G.
Published: September 2007

Respiratory infections are the main causes of chronic or recurrent cough in children. Children present 3.8–8 infective episodes per year with cough lasting, on average, 1–3 wk and 10% will still have cough after 4 wk. There is evidence of over‐treatment of cough with antibiotics, anti‐asthmatic drugs (in Italy) and symptomatic treatments, all with insufficient evidence of efficacy. The relation between sinusitis, asthma and isolated cough is possibly overemphasized. Cough is a symptom of sinusitis, but one can rarely expect isolated persistent or recurrent cough as the only symptom. The issue of chronic cough as the only sign of asthma has been extensively investigated. Recent literature established that the majority of children with isolated cough do not have asthma in terms of both absence of signs of typical asthma inflammation and response to steroid treatment. This unconfirmed hypothesis has unfortunately often resulted in a misunderstood use of inhaled steroids as ‘symptomatic’ treatment. Our aim should be to avoid unnecessary medicalization and lessen anxiety not by simply prescribing, but by spending time in evaluating patients and explaining to parents what are mostly physiological events, which should resolve spontaneously over time.
Difficult asthma: possible association with rhinosinusitis
Authors: Peroni D. G. , Piacentini G. L. , Ceravolo R. , Boner A. L.
Published: September 2007

Difficult asthma is rare in childhood; when child’s asthma is difficult to control, review of the diagnosis and evaluation of the different risk factors for exacerbations are recommended. The relationship between rhinosinusitis and bronchial asthma is provided by epidemiologic data. Doubts persist as to whether rhinosinusitis worsens asthma, or whether these are manifestations in different parts of the respiratory tract of the same underlying disease process. However, nasal sinus disease may contribute to less control in asthma, and patients with severe asthma appear to have the most prominent abnormalities on computed tomography scanning of the paranasal sinuses. From a pathogenetic point of view, many inflammatory mediators and the cellular infiltrate are often the same in the two entities, with a relevant role probably played by eosinophils. Antibiotic treatment of chronic sinus disease in asthmatic children may improve subjective asthmatic symptoms, lung function, and decrease bronchial hyperreactivity. Scientific evidence confirms that there may be an association between asthma and sinusitis even in childhood asthma: this could be relevant for diagnostic and therapeutic purposes.
Exhaled nitric oxide in children with asthma and sinusitis
Authors: Carraro S. , Gottardi G. , Bonetto G. , Baraldi E.
Published: September 2007

Exhaled nitric oxide (FENO) is a surrogate marker of eosinophilic airway inflammation. The measurement of this gas can be easily performed in children and the result is immediately available. Because of these characteristics, measurement of FENO is slowly becoming part of the routine clinical evaluation of an asthmatic patient. FENO measurement may have a role both in the diagnosis of asthma and as a guide in therapy algorithms. For example when FENO levels are persistently normal and the asthmatic child is asymptomatic, the steroid therapy may be decreased or even stopped. In patients with acute or chronic rhinosinusitis the levels of nasal nitric oxide (nNO) are significantly decreased, while they rise up after a course of antibiotics. The measurement of nasal NO has been proposed as a functional test to evaluate sinus ventilation. Nasal NO is significantly reduced also in primary ciliary dyskinesia and can be used as a screening tool to identify patients affected by this condition.
Paranasal sinuses and middle ear infections: what do they have in common?
Authors: Marchisio P. , Ghisalberti E. , Fusi M. , Baggi E. , Ragazzi M. , Dusi E.
Published: September 2007

Otitis media and sinusitis are among the most common pediatric diseases and they share common features. Although the anatomy, physiology and disease processes are not identical, knowledge of the pathophysiology of middle ear disorders often provides to the pediatrician a useful understanding of sinus diseases. The same risk factors identified for otitis media may play a pivotal role in the development of sinusitis. Moreover, as both paranasal sinuses and middle ear acquire respiratory pathogens from nasopharynx, acute sinusitis is usually caused by the same bacterial pathogens that cause acute otitis media, with a major role for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, while anaerobes may predominate in chronic disease. A responsibility of bacterial biofilms in chronic sinusitis, similarly to otitis media, has been recently suggested. Biofilms, three‐dimensional aggregates of bacteria, are refractory to antibiotics and thus might explain why some patients improve while on antibiotics but relapse after completion of therapy.
Sinusitis and Eustachian tube dysfunction in children
Authors: Leo G. , Piacentini E. , Incorvaia C. , Consonni D.
Published: September 2007

Because of its anatomic and functional connections, middle ear disorders frequently occur in sinusitis. Its prevalence, however, is likely to be underestimated. We evaluated the prevalence of Eustachian tube dysfunction in children with chronic sinusitis, in a large group of patients with chronic respiratory symptoms and its possible relationship with respiratory allergy. From a population of 1810 children with respiratory symptoms referred to our Pediatric Allergy Center, subjects with chronic sinusitis diagnosed by clinical criteria were selected. The children underwent testing of Eustachian tube function by tympanometry and of allergy by skin tests with common environmental allergens. Patients were divided into three groups according to age: group 1, <3 yr; group 2, between 3 and 6 yr, group 3, older than 6 yr. Overall 402 children (22.2%) had clinical diagnosis of chronic sinusitis according to the established criteria. Thirty‐three patients were in group 1, 299 in group 2, and 70 in group 3. Altered middle ear pressure was found in 69.1% of patients, with a significantly higher rate of altered tympanograms in younger children (p = 0.001). A positive skin‐prick test was found in 29.8% of children, with a significantly higher rate of positivity in older children (p = 0.015). The decrease in the rate of Eustachian tube dysfunction with age is likely to be associated with the anatomic development of the upper airways, while the presence of atopy does not seem to play a role in their occurrence.
Imaging techniques in the diagnosis and management of rhinosinusitis in children
Authors: Triulzi F. , Zirpoli S.
Published: September 2007

Sinusitis in children is a common problem. The diagnosis of both acute and chronic rhinosinusitis in the pediatric population, should be made first of all clinically, and not on the basis of imaging findings alone. Plain radiography may be used as a screening method for various pathological conditions of sinuses, but computed tomography (CT) remains the study of choice for the imaging evaluation of acute and chronic rhinosinusitis. In acute sinusitis, CT is indicated in patients with symptoms persisting after 10 days of appropriate therapy and in patients with suspected complications (especially in the brain and in the orbit). In addition to CT scanning, magnetic resonance (MR) imaging of the sinuses, orbits, and brain should be performed whenever extensive or multiple complications of sinusitis are suspected. In chronic sinusitis, CT scanning is the ‘gold standard’ for the diagnosis and the management, because it also provides an anatomic road map, when surgery is required. Nuclear medicine studies and ultrasound are rarely indicated in acute and chronic rhinosinusitis.
Cytology in the diagnosis of rhinosinusitis
Authors: Gelardi M. , Fiorella M. L. , Leo G. , Incorvaia C.
Published: September 2007

Nasal cytology is a diagnostic tool currently used in rhinology, with the aim of assessing cell changes in the nasal epithelium exposed to irritant or inflammatory agents. Its rationale is based on the knowledge that nasal mucosa of healthy individuals is constituted by four cytotypes (ciliata, mucipara, striata, and basalis) and does not show other cells except, rarely, neutrophils and, very rarely, bacteria. In this view, the detection of a given cell type different from these is a sign of possible pathology. The advantage and the diffusion of nasal cytology were increased by a number of factors such as the easiness of performance, the non‐invasiveness allowing repetition (which is often needed in the efficacy monitoring of medical or surgical treatment of nasal diseases), and the low cost. This makes nasal cytology particularly feasible for application in children. The cytological feature characterizing infectious inflammation is the presence of abundant bacteria, which may be found in extracellular tissue and also inside neutrophils as a result of phagocytosis. In such clinical condition it is important to monitor the disease with cytological controls to verify the significant decrease, or the disappearance of inflammatory cells, which indicates the resolution of the pathology.
From clinical practice to guidelines: how to recognize rhinosinusitis in children
Authors: Esposito S. , Bosis S. , Bellasio M. , Principi N.
Published: September 2007

Rhinosinusitis is a common childhood respiratory infection. Children have approximately six to eight viral infections of the upper respiratory tract each year, 5–13% of which may be complicated by a secondary bacterial infection of the paranasal sinuses. The diagnosis of acute bacterial rhinosinusitis in children is established by the persistence of purulent nasal or post‐nasal draining lasting at least 10 days, especially if accompanied by supporting symptoms and signs, at which point antibiotic treatment has to be recommended. Appropriate antibacterial therapy should also be recommended if the draining has been present for less time, but is concomitantly associated with significant fever and localized signs of sinus inflammation in a child who appears ill. Imaging studies are not necessary to confirm the diagnosis of clinical rhinosinusitis for the purposes of treatment, but should be reserved for cases in which the diagnosis is in doubt or a complication is suspected, and for patients with recurrent or chronic rhinosinusitis. Under these circumstances, computed tomography is the preferred evaluation. Together with their clinical judgment, these suggestions may be useful for pediatricians in diagnosing this common condition.
Systemic treatment of rhinosinusitis in children
Authors: Novembre E. , Mori F. , Pucci N. , Bernardini R. , Vierucci A. , Martino M. de
Published: September 2007

Systemic acute rhinosinusitis therapy consists mostly of antibiotic treatment because pathogens play a major role. Amoxicillin is the drug of choice for treatment of acute rhinosinusitis, with second‐ and third‐ generation cephalosporins, azythromycin, clarithromycin, and telithromycin as possible options, especially in the case of allergy to amoxicillin. If the clinical course suggests that an anaerobic pathogen is more likely, clindamycin or metronidazole can be considered in combination with a broad‐spectrum drug. In antimicrobial treatment of chronic sinusitis there is no consensus on treatment length, organism coverage, or which antibiotics are most effective because the bacteriology is variable with polymicrobial anaerobic and aerobic organisms present. Adjuvant therapies need to be proven by additional studies. Chronic rhinosinusitis is heterogeneous and treatment should vary according to the causative factor involved. Short courses of systemic steroids have been found very useful to decrease mucosal swelling and inflammation in chronic rhinosinusitis. However, no randomized controlled studies have been performed to validate their efficacy in children. A variety of other agents are used in the treatment of chronic rhinosinusitis including antihistamines, decongestants, and leukotriene modifiers. To date, there is no good evidence from randomized controlled studies to support the use of any of these agents in the treatment of this disease in either children or adults.
Topical treatment of rhinosinusitis
Authors: Fiocchi A. , Sarratud T. , Bouygue G. R. , Ghiglioni D. , Bernardo L. , Terracciano L.
Published: September 2007

We reviewed current clinical evidence for the use of topical treatments in pediatric rhinosinusitis. Repeated Entrez PubMed searches were done using the template algorithm [rhinosinusitis AND (…)] with the settings: [Humans; English; All Child 0–18; Clinical trial; Last 10 yr] for the following comparators: steroid, irrigation, saline, antihistamine, decongestant, antibiotic, antimycotic, fungicide. The authors’ clinical experience in the pediatric allergy unit of a university hospital was also drawn upon. Pediatric studies were retrieved but only one satisfied current evidence‐based medicine standards for reporting clinical trials. Studies could not be systematized because of methodological, analytical, and interpretation biases. While saline irrigation, nasal decongestants, steroids, antibiotics, antihistamines and fungicides are all in widespread pediatric use, comparing studies from the literature for evidence of efficacy implied subjective appraisal, except in the case of topical steroids. Evidence for the efficacy of topical treatment for pediatric rhinosinusitis is narrative albeit this modality cannot be excluded from individualized patient protocols on the basis of the clinical literature alone. With the exception of topical steroids, no weighable evidence of effectiveness supports the premise that topical treatments actually serve the purpose for which they are widely prescribed in pediatrics.
Rhinosinusitis in children: the role of surgery
Authors: Felisati G. , Ramadan H.
Published: September 2007

Indications and nature of surgery for chronic rhinosinusitis (CRS) have yet to be elucidated in children. After review of the literature and based on their experience, the authors suggest guidelines for the treatment of CRS in children. They suggest grouping children with rhinosinusitis into two groups: those with complicated acute rhinosinusitis and those with CRS. For the first group, the authors suggest an early surgical intervention because of the potential serious consequences and sometimes irreversible damage. For the second group, most agree that maximal medical management should be the first line of treatment with antibiotics, nasal lavage and as a last resort surgery. It is important to realize that surgery should be considered in these cases if medical treatment fails. Once surgery is recommended, the kind of surgery then becomes an issue between adenoidectomy, endoscopic sinus surgery or a combination of the two depending on the age and other conditions.
Rhinosinusitis: prevention strategies
Authors: Duse M. , Caminiti S. , Zicari A. M.
Published: September 2007

Risk factors of recurrent sinusitis involve upper respiratory infections, bacterial load of the adenoids, day care attendance and exposure to tobacco smoke as well as sinonasal abnormalities, including septal deviation, choanal atresia, polyps and hypoplasia of sinuses. Furthermore, several systemic disorders can facilitate the development of chronic sinusitis, such as allergic rhinitis, gastro‐esophageal reflux disease (GER), cystic fibrosis, primary ciliary dyskinesia, and immunodeficiency diseases. A clinical practice guideline for the management of sinusitis is available only for the acute disease, but does not include for the management of the chronic form (i.e. chronic/recurrent sinusitis) and even less for the prevention strategies. As several studies indicate that the majority of children respond to sequential medical followed by surgical interventions, when needed, the best prevention of recurrence or chronicity is to properly treat acute sinusitis; in addition, children should be removed from larger and crowded day care whenever possible and should not be exposed to cigarette smoke. If allergic rhinitis co‐exists, it can be managed with nasal steroids sprays and anti‐histamines, although the long‐term results are controversial. In case of chronic sinusitis, the strategy of prevention is to assess and to cure the associated conditions.
Pediatric liver transplantation: Review of literature 2005–2006
Authors: Mazariegos George V. , Machaidze Zurab
Published: September 2007

Abstract:  Recent published literature in pediatric liver transplantation continues to demonstrate the unique areas that distinguish pediatric liver transplantation from the adult discipline. Published accounts of disease states leading to pediatric transplantation, outcome analysis, reviews of immunosuppressive drug trials, technical progress, organ allocation and policy all highlight unique aspects of pediatric care. We have chosen significant contributions from the several hundred scientific articles related to clinical pediatric liver transplantation published from August 2005 through December 2006 and summarized them for the reader. When appropriate, comments synthesizing common threads across one or more manuscripts were included and the reader is urged to refer to the actual manuscript for more in depth understanding. Nonetheless, we anticipate this review will serve as a suitable introduction to the most significant areas affecting care for children who await or undergo liver transplantation.
Favorable outcome with allogeneic hematopoietic stem cell transplantation in pediatric acquired aplastic anemia patients
Authors: Unal Sule , Çetin Mualla , Tavil Betül , Çalışkan Neslihan , Yetgin Sevgi , Uçkan Duygu
Published: September 2007

Abstract:  The data of allogeneic HSCT in nine children with acquired AA between June 1998 and July 2006 were analyzed retrospectively. The median duration of time to neutrophil and platelet engraftment was 18 and 25 days, respectively. None of the patients had primary graft failure. Two (22.2%) patients developed acute GVHD and of these, one (11.1%) was Grade 1, and the other (11.1%) was Grade 3. Although the study group was composed of higher risk patients, including six of nine resistant to previous immunosuppressive treatment, eight had multiple not irradiated or filtered transfusion histories and one of the cases was only 5/6 HLA‐compatible with his donor, the five‐yr overall and EFS was 100%, and all recipients are alive without any graft failure. This may be attributed to the dose adjusted use of ATG according to individual transfusion history and gradual tapering of CsA and cessation at least nine months after allogeneic HSCT.
Successful HLA‐identical hematopoietic stem cell transplantation in a patient with purine nucleoside phosphorylase deficiency
Authors: Delicou Sophia , Kitra‐Roussou Vassiliki , Peristeri Julia , Goussetis Eugenios , Vessalas George , Rigatou Eftymia , Psychou Fotini , Salavoura Katerina , Grafakos Stelios
Published: September 2007

Abstract:  PNP deficiency is an autosomal recessive metabolic disorder characterized by severe combined immunodeficiency, autoimmune hemolytic anemia, and by a complex of neurologic manifestations including ataxia, developmental delay, and spasticity. PNP protein catalyzes the phosphorolysis of deoxyinosine and deoxyguanosine. It is found in most tissues of the body but is expressed at the highest levels in lymphoid tissues. This tissue distribution explains why the lymphoid system is predominantly affected in PNP deficiency. We describe a five‐yr‐old boy with muscular hypertonia, impaired growth, autoimmune hemolytic anemia, and neutropenia who underwent HSCT from his HLA‐identical sister. One yr post‐HSCT, the boy developed normal immunological functions, and his neurological status improved.
Pediatric renal transplantation – A single center experience of 15 yr from India
Authors: Chacko Bobby , Rajamanickam Timothy , Neelakantan Nithya , Tamilarasi V. , John George T.
Published: September 2007

Abstract:  Renal transplantation is the optimal treatment for children with ESRD. We undertook this study to establish the outcome of pediatric renal transplants in a resource‐constrained environment in a developing country. A retrospective analysis on 90 pediatric renal transplants (age at transplant ≤18 yr) done at our center over a 15 yr period was analyzed. The mean age of the recipients was 15 yr (range 6–18 yr) accounting for 6.1% of all the renal transplants done at our center (90/1472). Ninety‐six percent of patients received kidneys from live‐related donors. The major causes of ESRD were glomerulonephritis (28%) and urological abnormalities (17%), while the etiology was unknown in 50%. Immunosuppression was based on a triple drug regimen consisting of prednisolone, CsA and azathioprine in 98% of children. Amongst complications, any acute rejection episodes (46.7%), UTI (26.7%) and CMV disease (16.7%) predominated. The mean duration of follow‐up was 42 ± 33 month (range 3–159 month). Graft loss occurred in nine (10%) children at a mean duration of 25 ± 22 month (range 6–70 month). Overall 1‐, 5‐, and 10‐yr graft survival was 98%, 84% and 76%. Overall 1‐, 5‐, and 10‐yr patient survival was 95%, 87%, and 79%. The significant predictors of graft loss were CMV disease (p = 0.018) and >2 rejection episodes (p = 0.05), while sepsis (p = 0.01) was the most important contributor to patient loss. Pediatric renal transplantation in India can be accomplished successfully. The graft and patient survival in our study, the largest from India, is comparable to those published from developed countries and is encouraging given the limited resources.
Pseudotumoral azygos and paraesophageal varices of posterior mediastinum in a 15‐month‐old infant: A case report
Authors: Yang Fuchun , Takada Yasutsugu , Sakamoto Seisuke , Okamoto Shinya , Uemoto Shinji
Published: September 2007

Abstract:  A case of azygos and paraesophageal varices presenting as a posterior mediastinal mass in a 15‐month‐old infant with biliary atresia is described. The patient was evaluated for living donor liver transplantation because of repeated cholangitis after Kasai operation, and plain CT scan demonstrated a mass in posterior mediastinum. The operation of mediastinal tumor resection was planned before liver transplantation in order to exclude malignant disease, however, possibility of paraesophageal varices remained. Contrast‐enhanced magnetic resonance imaging clearly demonstrated azygos and paraesophageal varices in posterior mediastinum. Living donor liver transplantation was performed successfully without ligation of paraesophagogastric varices. Contrast‐enhanced CT demonstrated distinctly decreased mediastinal mass one month after transplantation.
The effect of glutamine supplementation on hematopoietic stem cell transplant outcome in children: A case–control study
Authors: Kuskonmaz Baris , Yalcin Songul , Kucukbayrak Ozlem , Cetin Nevin , Cetin Mulla , Tezcan Ilhan , Uckan Duygu
Published: September 2007

Abstract:  HSCT associated morbidity and mortality is usually attributed to high‐dose chemotherapy/radiotherapy regimens used for conditioning. Glutamine (Gln), a conditionally essential amino acid during severe catabolic states, has been shown to have favorable effects in patients with malignancies and in those undergoing HSCT. However, controversy exists regarding its routine use. Studies in children investigating gln supplementation are very limited. In the present study, including 21 gln‐supplemented and 20 control pediatric patients, gln supplementation was shown to reduce the duration of fever and decrease the incidence of SOS during the HSCT course. In addition, a decrease in drug‐related toxicity and a trend toward reduced incidence of severe mucositis were observed.
De novourothelial carcinoma in a pediatric recipient of living donor kidney graft
Authors: Wu Chan‐Yao , Hung Shih‐Yuan , Su Yu‐Tsun , Chang Hong‐Cheng , Yu Tsan‐Jung
Published: September 2007

Abstract: De novourothelial carcinoma is relatively rare among post‐transplant malignancies and never reported in pediatric kidney transplant recipients. In this paper, we reported one 12‐yr‐old male case with painless gross hematuria as the initial manifestation ofde novourothelial carcinoma in living donor graft pelvis. We emphasize the importance that cystoscopy and retrograde pyelography of native and transplant kidneys should be performed in all kidney transplant recipients with painless gross hematuria.
Human adipose tissue‐derived mesenchymal stromal cells as salvage therapy for treatment of severe refractory acute graft‐vs.‐host disease in two children
Authors: Fang Baijun , Song Yongping , Lin Quande , Zhang Yanli , Cao Ying , Zhao Robert Chunhua , Ma Yuanfang
Published: September 2007

Abstract:  Severe GVHD is a lethal complication to ASCT, and a number of approaches are therefore being evaluated. Recently, Le Blanc et al. reported a case of grade IV therapy‐resistant acute GVHD of the gut and liver that showed rapid improvement after infusion of mesenchymal stem cells. Here we describe two pediatric patients who developed severe refractory acute GVHD following ASCT and were successfully treated with AMSC from HLA‐mismatched unrelated donors.
Outcome of management strategies for BK virus replication in pediatric renal transplant recipients
Authors: Puliyanda Dechu P. , Toyoda Mieko , Traum Avram Z. , Flores Francisco X. , Jordan Stanley , Moudgil Asha , Somers Michael J. G.
Published: September 2007

Abstract:  Management of BKV infection is not well defined. Eighteen pediatric renal transplant patients with BKV‐PCR (+) were divided into three groups; Group 1: Viruria only (6), Group 2: Viremia with stable GFR (4), Group 3: Viremia with >25% decline in GFR and BKVAN on biopsy (8). With initial BKV‐PCR(+), Group 1 received no treatment; Group 2 had MMF reduced 30%; Group 3: 6/8 had CNI discontinuation, 2/8 had reduced MMF and cidofovir. BKV, GFR and histology were compared pre‐ and post‐treatment. In Group 1 viruria decreased in all patients; GFR remained stable. Group 2 showed reduced viremia with no GFR change. Group 3 showed reduced viremia in 8/8 patients. Patients with >50% decline in GFR from baseline (6/8) showed worse histology: 2/6 lost grafts despite no BKV on follow‐up biopsy. Our results show that with viruria alone no treatment is necessary; with viremia and stable GFR, reduced immunosuppression decreases viremia and maintains GFR. With viremia and reduced GFR, immunosuppression reduction with or without cidofovir decreases viremia and stabilizes GFR in most patients. Greater than 50% reduction in GFR at BKVAN diagnosis correlates with risk for graft loss. Serial monitoring of BKV viremia with early intervention may prevent BKVAN graft loss in children.
Hyperacute graft‐vs.‐host disease after related HLA‐identical umbilical cord blood transplantation
Authors: Kuskonmaz Baris , Gocer Safak , Ersoy‐Ewans Sibel , Cetin Ozman Fatma , Cetin Mualla , Uckan Duygu
Published: September 2007

Abstract:  haGVHD has been described following bone marrow and peripheral blood stem cell transplantation and in a single case who received unrelated HLA mismatched CB. An unusual case of haGVHD following HLA 6/6‐matched sibling CBT in a child with AML is presented. The development of haGVHD in a fully matched CBT and without precipitating factors may suggest the role of still undefined and perhaps individual contributory factors.
An intrarenal abscess as presenting symptom of an infection with Nocardia farcinica in a patient after renal transplantation
Authors: Van Luin A. , Manson W.L. , Van Der Molen L. , Van Der Heide J.J. Homan , Van Son W.J.
Published: September 2007

Abstract: A 52‐year‐old man presented 8 months after transplantation with an intrarenal mass, which proved to be caused by an infection with Nocardia farcinica. Because of the potential fatal course of nocardiosis, transplantectomy was performed and long‐term antibiotic treatment was instituted. Three‐and‐a‐half years later, this patient underwent successful re‐transplantation under co‐trimoxazole prophylaxis. At present, more than 1 year after his second transplant has been performed, there are no signs of recurrence of Nocardia infection. To our knowledge, this is the first report of a patient with nocardiosis with an intrarenal abscess as presenting symptom.
The role of blood services and regulatory bodies in stem cell transplantation
Authors: Austin E. B. , Guttridge M. , Pamphilon D. , Watt S. M.
Published: September 2007

Advances in stem cell research over the past few decades have coincided with large increases in haemopoietic stem cell transplantation (HSCT) using either bone marrow, peripheral blood or cord blood‐derived stem cells. Alongside this growth has come an increase in the role played by regulatory bodies, both governmental and professional, to ensure that those undertaking such procedures do so in a manner so as to minimize the risk to patients. Interestingly, government legislation encompasses not only cellular therapies, but also the use of tissues and organs, as many of the processes and procurement procedures involved are similar. In this review, we analyse the trends in HSCT, describe the development and impact of legislation within Europe on this practice and outline the vital role played by the UK blood services in providing robust and high‐quality HSCT services.
Human parvovirus PARV4 in clotting factor VIII concentrates
Authors: Fryer J. F. , Hubbard A. R. , Baylis S. A.
Published: September 2007

Background and Objectives  Parvoviruses are small non‐enveloped DNA viruses, relatively resistant to virus inactivation procedures. The recently identified human parvovirus PARV4, including a related genotype 2 virus (also termed PARV5), has been found to be a contaminant of pooled plasma used in the manufacture of plasma‐derived products. This report describes an investigation to determine whether PARV4 is present in clotting factor concentrates.

Materials and Methods  Factor VIII concentrates manufactured in the past 30–35 years were screened for PARV4 and human parvovirus B19 (B19V) sequences. Viral loads in products testing positive for PARV4 were quantified using a consensus TaqMan assay designed to a highly conserved region. DNA sequence analysis was performed to confirm the genotypes present.

Results  From a total of 175 lots of factor VIII concentrate, 28 of these contained PARV4 sequences, and in two lots both genotypes 1 and 2 were found to be present. The highest viral loads observed exceeded 105 copies per ml. The majority of factor VIII concentrates testing positive for PARV4 were manufactured in the 1970s and 1980s. Human B19V was also a frequent contaminant of these products.

Conclusions  PARV4 was detected in 16% of factor VIII concentrates, particularly in older batches from the 1970s and 1980s. The significance in terms of the viral safety and potential transmission to recipients of these products is not yet known.
Effects of Filtration of Semen Doses from Subfertile Boars through Neuter Sephadex Columns
Authors: Bussalleu E , Pinart E , Rivera MM , Arias X , Briz M , Sancho S , García‐Gil N , Bassols J , Pruneda A , Yeste M , Casas I , Rigau T , Rodriguez‐Gil JE , Bonet S
Published: September 2007

Contents

This study was designed to develop a method of improving the quality of sperm obtained from subfertile Piétrain boars. Seminal doses were filtered through neuter SephadexTM columns (G‐25 Medium, G‐50 Fine, G‐50 Medium and G‐75, length 10 ± 0.5 cm, flow rate 1 ml/20 s). Doses were prepared by pooling 10 ml semen samples collected from 58 asthenoteratospermic boars and diluted the sperm‐cell rich fraction 1 : 6 in Betsville thawing solution extender. Sperm quality was determined before and after the filtering process. Sperm morphology and motility were assessed using the computer program sca®2002 production, and sperm vitality was evaluated by fluorescence multistaining. ORT and HRT tests were used to determine the osmotic resistance of spermatozoa, and metabolic performance was assessed by measuring l‐lactate production. Results indicate that the filtration process rendered increased proportions of mature spermatozoa and of viable spermatozoa with an intact acrosome, nucleus and mitochondrial sheath. Sperm filtration led to decreased percentages of spermatozoa with proximal and distal droplets and of agglutinated spermatozoa, along with slightly diminished ORT values. HRT scores and l‐lactate production were unaffected. Our findings indicate that filtering through a Sephadex column improves the sperm morphology and vitality of seminal doses obtained from subfertile boars, but produces no functional changes in the spermatozoa. All four column types yielded similar results.
Informing rural and remote students about careers in health: Factors influencing career decisions
Authors: Buikstra Elizabeth , Eley Robert M. , Hindmarsh Natalie
Published: September 2007

Objective:  Since 1994 a state‐wide program has been operating in Queensland to provide non‐metropolitan secondary school students with information about health careers. Determination of the factors influencing the career decisions of rural and remote students was one objective of the evaluation of that program.

Design:  Telephone interviews.

Setting:  Secondary schools.

Subjects:  People who had previously attended Year 10 residential health career workshops run by Queensland Health. Ninety‐four of 277 past participants to Year 10 Health Careers Workshops responded to a postal questionnaire and were invited to take part in a telephone questionnaire to collect further information related to the course and career choices.

Main outcome measures:  Self‐reported factors affecting career decisions of students from rural and remote areas.

Results:  Of the 94 past workshop participants, interviews were held with 70. All participants had left secondary education and had either undertaken or were undertaking some form of tertiary study. The most influential of nine factors to both undergraduate and postgraduate course choices was self‐interest. Various other factors differentially contributed to undergraduate and postgraduate course choices among them were the health careers workshops, which played a major influence on undergraduate course decisions of students.

Conclusion:  Self‐interest is the largest self‐reported factor to career decision making among students from rural and remote areas. Finance and career advice from school are not considered to be highly influential. However, these independent decisions can be substantially influenced by external information provided through health career workshops.