Showing papers by "Hospital for Sick Children published in 2004"

The functional landscape of mouse gene expression

Abstract: Large-scale quantitative analysis of transcriptional co-expression has been used to dissect regulatory networks and to predict the functions of new genes discovered by genome sequencing in model organisms such as yeast. Although the idea that tissue-specific expression is indicative of gene function in mammals is widely accepted, it has not been objectively tested nor compared with the related but distinct strategy of correlating gene co-expression as a means to predict gene function. We generated microarray expression data for nearly 40,000 known and predicted mRNAs in 55 mouse tissues, using custom-built oligonucleotide arrays. We show that quantitative transcriptional co-expression is a powerful predictor of gene function. Hundreds of functional categories, as defined by Gene Ontology 'Biological Processes', are associated with characteristic expression patterns across all tissues, including categories that bear no overt relationship to the tissue of origin. In contrast, simple tissue-specific restriction of expression is a poor predictor of which genes are in which functional categories. As an example, the highly conserved mouse gene PWP1 is widely expressed across different tissues but is co-expressed with many RNA-processing genes; we show that the uncharacterized yeast homolog of PWP1 is required for rRNA biogenesis. We conclude that 'functional genomics' strategies based on quantitative transcriptional co-expression will be as fruitful in mammals as they have been in simpler organisms, and that transcriptional control of mammalian physiology is more modular than is generally appreciated. Our data and analyses provide a public resource for mammalian functional genomics.

Comparing rates of psychiatric and behavior disorders in adolescents and young adults with severe intellectual disability with and without autism.

Abstract: Eight males and four females with an Autism Diagnostic Interview-Revised (ADI-R) diagnosis of autism (mean age of 16.3 years) and severe intellectual disability (IQ < 40) were individually matched to controls on the basis of chronological age, gender, and nonverbal IQ. The dependent measure was the Diagnostic Assessment for the Severely Handicapped-II, which is used to screen for psychiatric and behavior disorders in lower-functioning individuals. Participants with autism showed significantly greater disturbances as measured by the Diagnostic Assessment for the Severely Handicapped-II total score and seven of 13 subscales. They also averaged 5.25 clinically significant disturbances compared with 1.25 disturbances for participants without autism. Specific vulnerabilities to anxiety, mood, sleep, organic syndromes, and stereotypies/ tics were found in the participants with comorbid autism.

The Strengths and Difficulties Questionnaire overseas: evaluations and applications of the SDQ beyond Europe.

Abstract: During the few years that have passed since it became available, the Strengths and Difficulties Questionnaire (SDQ) has been extensively evaluated and widely applied to assess behaviour disorders of children and adolescents in European countries. In contrast, relatively few reports have published SDQ results obtained in other parts of the world, although its briefness and availability in over 40 languages make this instrument particularly attractive for international collaborations and cross-cultural comparisons concerning clinical and epidemiological issues. This initial overview summarises some of these non-European experiences with the SDQ by presenting a selection of projects that have either psychometrically evaluated this novel questionnaire, applied it to screen for behaviour disorders, or employed its parent-, teacher- or self-rated versions as research tools. Since a large part of the mentioned studies are ongoing or have only recently been completed, much of the work reported here is still unpublished. Across a huge variety of cultures and languages, experience gained with the SDQ in other continents has supported European evidence of good psychometric properties and clinical utility of this questionnaire. Since worldwide usage of the SDQ can be expected to increase in the future, more international coordination is encouraged, in order to fully exploit the promising potentials of this versatile assessment tool and systematically investigate cross-cultural differences and similarities in child and adolescent behaviour.

Permissive hypercapnia — role in protective lung ventilatory strategies

Abstract: ‘Permissive hypercapnia’ is an inherent element of accepted protective lung ventilation. However, there are no clinical data evaluating the efficacy of hypercapnia per se, independent of ventilator strategy. In the absence of such data, it is necessary to determine whether the potential exists for an active role for hypercapnia, distinct from the demonstrated benefits of reduced lung stretch. In this review, we consider four key issues. First, we consider the evidence that protective lung ventilatory strategies improve survival and we explore current paradigms regarding the mechanisms underlying these effects. Second, we examine whether hypercapnic acidosis may have effects that are additive to the effects of protective ventilation. Third, we consider whether direct elevation of CO2, in the absence of protective ventilation, is beneficial or deleterious. Fourth, we address the current evidence regarding the buffering of hypercapnic acidosis in ARDS. These perspectives reveal that the potential exists for hypercapnia to exert beneficial effects in the clinical context. Direct administration of CO2 is protective in multiple models of acute lung and systemic injury. Nevertheless, several specific concerns remain regarding the safety of hypercapnia. At present, protective ventilatory strategies that involve hypercapnia are clinically acceptable, provided the clinician is primarily targeting reduced tidal stretch. There are insufficient clinical data to suggest that hypercapnia per se should be independently induced, nor do outcome data exist to support the practice of buffering hypercapnic acidosis. Rapidly advancing basic scientific investigations should better delineate the advantages, disadvantages, and optimal use of hypercapnia in ARDS.

Depression during Pregnancy : Overview of Clinical Factors.

Abstract: Depression during pregnancy is common, affecting an estimated 20% of women. However, conflicting data exist concerning the outcomes of this disorder. Thus, we reviewed studies that presented evidence for the use of antidepressants and those that examined untreated depression during the gestational period, in terms of clinical and epidemiological aspects. Observational studies have provided reassuring evidence of the safety of antidepressant use during pregnancy. However, due to the reluctance of healthcare providers to prescribe and patients to take medication during the obstetric period, approximately three-quarters of those diagnosed with depression remain untreated. Furthermore, healthcare providers apparently do not recognise the disorder in up to 50% of pregnant women who experience depression. Increased antidepressant dosing during pregnancy may be required to maintain euthymia; however, guidelines for effective dosing levels are absent. Consequently, many patients remain inadequately treated. Substantial maternal and fetal morbidity including substance abuse, functional impairment, increased risk of postnatal depression, and poor pregnancy outcomes have resulted from untreated depression. The consequences of those outcomes are likely to be associated with substantial clinical, social and economic burdens. An incidence-based assessment of the consequences of prenatal depression would be useful in order to: (i) establish the impact on the quality of life of these patients and their families; (ii) assess the associated economic burden on individual families and the healthcare system; and (iii) to provide epidemiological data to enable the provision of suitable management strategies for these patients.

Malformation rates in children of women with untreated epilepsy: a meta-analysis.

Abstract: Background: It is widely quoted that women with epilepsy have a higher than baseline risk for giving birth to a child with malformations, independent of the effects of antiepileptic drugs.

Tapping the Perspectives of Children Emerging Ethical Issues in Qualitative Research

Abstract: The unique ethical issues related to conducting research with children are insufficiently distinguished from issues in working with vulnerable groups, despite a shift to recognizing children as act...

The role of emotional social support in the psychological adjustment of siblings of children with cancer

Abstract: Background Siblings of children with cancer are at risk for reduced emotional support. The role of emotional social support in the psychological adjustment of siblings of paediatric cancer patients was examined, in the context of age and gender. Methods The sample consisted of two groups of siblings of children being treated for cancer: siblings referred for behaviour problems (n = 47) and a comparison group of non-referred siblings (n = 25). Forty-two were female, and 30 were male. The mean age was 10.31 years (SD = 2.71). Siblings completed measures of depression, anxiety, behaviour, and emotional social support. One parent of each sibling completed measures of sibling's behaviour and anxiety. Results Siblings who reported more social support endorsed significantly fewer symptoms of depression, anxiety, and fewer behaviour problems, and their parents reported less anxiety and fewer behaviour problems than siblings who reported lower social support. Parents of referred siblings reported significantly more behaviour problems than parents of non-referred siblings. Referred adolescent females reported significantly higher depression scores and were perceived as more anxious than referred adolescent males and non-referred adolescent females. Non-referred younger siblings with high social support were perceived by their parents as having the fewest behaviour problems. Conclusions High level of social support appears to play a protective role in psychological adjustment of siblings of paediatric cancer patients, with age and gender as modifying factors. Although not all siblings develop behaviour or emotional problems, it is critical to identify those who do in order to intervene accordingly.

Predictors and mediators of psychological adjustment in mothers of children newly diagnosed with cancer

Abstract: Early psychological adjustment (PA) of mothers of children with cancer (MCC) and mothers of children with acute illnesses (MCA) were compared, and predictors and mediators of maternal adjustment were tested. Sixty-nine MCC and 22 MCA completed standardized measures of depression, anxiety, global mental health (GMH), concurrent stress and strains, social support, coping strategies and child behavior. MCC reported greater depressive symptomatology, emotion-focused coping, and social support than did MCA. For MCC, emotion-focused coping and child behavior both predicted depression, anxiety, and GMH; concurrent stress and strain mediated the relationship between child behavior and depression and between emotion-focused coping and each measure of adjustment. For MCA, only emotion-focused coping predicted PA and concurrent stress and strains mediated the relationship between emotion-focused coping and depression. These findings suggest that MCC have more PA difficulties that are uniquely related to their child's behavior than MCA. Concurrent stress and strains seems to be an important mediator of PA for both groups of mothers. Copyright © 2003 John Wiley & Sons, Ltd.

Lung Inflammation as a Therapeutic Target in Cystic Fibrosis

Abstract: Cystic fibrosis (CF) lung disease is characterized by chronic neutrophilic inflammation and infection. Effective management of airway inflammation could complement other therapies for the treatment of CF. Recent progress has been made in understanding the signaling pathways regulating inflammatory cytokines in the lung. Here we examine the mechanisms responsible for inflammation in the CF lung, and discuss potential therapeutic strategies targeting inflammation.

High tidal volume ventilation causes different inflammatory responses in newborn versus adult lung.

Abstract: We investigated the effect of high VT ventilation on adult and newborn rats by examining pulmonary injury and cytokine messenger RNA (mRNA). On the basis of compliance, edema formation, and histology, ventilation with 25 ml·kg−1 was more injurious to adult rats than newborns. Ventilation with 40 ml kg−1 minimally affected compliance in newborns but caused death in adults. Ventilation of adults for 30 minutes at 25 ml kg−1 upregulated the mRNA expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-2 (MIP-2), and IL-10, whereas in newborns such ventilation only increased mRNA expression of MIP-2 and IL-10. When VT was raised to 40 ml kg−1 in newborns, IL-1β mRNA levels were additionally increased at 30 minutes, whereas ventilation for 3 hours additionally increased IL-6 and TNF-α mRNA. In newborns, the addition of 100% oxygen (O2) to 30 minutes of ventilation blunted the high VT induction of IL-1β, IL-10, and MIP-2 mRNA expressions, whereas at 3 hours, 100%...

Outcome of non-invasive positive pressure ventilation in paediatric neuromuscular disease

Abstract: Background: Non-invasive positive pressure ventilation (NPPV) has a beneficial effect on nocturnal hypoventilation and hospitalisation rates in adults with static or slowly progressive neuromuscular disease and respiratory failure. Its role in children affected with similar disease processes, however, remains unclear. Aims: To investigate the impact of NPPV on hospitalisations and sleep related respiratory parameters in children with neuromuscular disease. Methods: Fifteen children (mean age 11.7, range 3.4–17.8 years) diagnosed with neuromuscular disease who had been started on nocturnal NPPV and had at least one year of follow up since the initiation of such therapy were studied. Patients served as their own controls and comparison was made of the years preceding and following the initiation of NPPV. Results: Children spent 85% fewer days in hospital (mean pre-NPPV 48.0 days, mean post-NPPV 7.0 days) and 68% less days in intensive care after initiation of NPPV (mean pre-NPPV 12.0 days, mean post-NPPV 3.9 days). Sleep study parameters including number of desaturations, apnoea-hypopnoea index and transcutaneous pCO 2 levels improved after initiation of NPPV. Conclusions: NPPV can decrease hospitalisations for children with neuromuscular disease and improves sleep related respiratory parameters. A prospective study is now needed to further delineate the role of NPPV in this population of children.

Development of a health-related quality of life measure for boys with haemophilia: the Canadian Haemophilia Outcomes--Kids Life Assessment Tool (CHO-KLAT).

Abstract: Several measures of quality of life (QoL) are available for children with haemophilia. However, most are not disease-specific and few focus on children's perspectives. The purpose of this study was to develop a psychometrically sound measure of QoL that included the perspectives of boys with haemophilia. A list of potential items was developed from the literature, other measures, and input from five discussion sessions with adults with haemophilia, children with haemophilia and their parents and haemophilia nurses. The list was augmented with items generated by three focus groups with children and three focus groups with parents. These groups also prioritized items and recommended a domain structure. Supplemental information was gathered by surveying haematologists. Data from all sources were analysed to reduce the number of items using a two-step approach, based on rules that weighted the children's priorities most heavily. The remaining items were compiled into a questionnaire that was pilot tested with 10 children and their parents. The total item pool contained 228 potential items. Of these, 33 were removed based on three focus groups and survey responses, 72 were removed after the completion of all focus groups and 46 were removed due to redundancy. This resulted in a 77-item version of the CHO-KLAT. Pilot testing identified the need to subdivide two items, resulting in a 79-item CHO-KLAT. The CHO-KLAT is a promising disease-specific measure of QoL that reflects children's unique perspectives. This child-centric focus distinguishes the CHO-KLAT from alternative measures of QoL. Further research will assess the measurement properties of the CHO-KLAT.

Children in side-impact motor vehicle crashes: seating positions and injury mechanisms.

Abstract: Background:This study aimed to describe the injury mechanisms of children involved in side-impact car crashes, particularly as these relate to seating position, and to estimate the danger of the near-side seating position.Methods:A prospective two-center study of children involved in severe car cras

Retrovirally Mediated Overexpression of Versican V3 Reverses Impaired Elastogenesis and Heightened Proliferation Exhibited by Fibroblasts from Costello Syndrome and Hurler Disease Patients

Abstract: The phenotypic resemblance of patients with Costello syndrome and Hurler disease has been linked to impaired formation of elastic fibers that coincides with elevated cellular proliferation. Impaired elastogenesis in these diseases associates with respective abnormal accumulation of chondroitin sulfate and dermatan sulfate proteoglycans that induce cell surface shedding of elastin-binding protein (EBP) normally required for intracellular chaperoning of tropoelastin and its assembly into elastic fibers. A variant of the chondroitin sulfate proteoglycan versican, V3, which lacks chondroitin sulfate, has recently been shown to stimulate elastic fiber assembly and decrease proliferation when expressed by retroviral transduction in arterial smooth muscle cells. However, the mechanism(s) by which V3 influences this phenotype is not known. We now demonstrate that transduction of skin fibroblasts from Costello syndrome and Hurler disease patients with cDNA to versican V3 completely reverses impaired elastogenesis and restores normal proliferation of these cells. This phenotypic reversal is accompanied by loss of chondroitin sulfate from the cell surface and increased levels of EBP. Versican V3 transduction of skin fibroblasts from GM 1 -gangliosidosis patients, which lack EBP, failed to restore impaired elastogenesis. These results suggest that induction of elastic fiber production by gene transfer of versican V3 in skin fibroblasts is mediated by rescue of the tropoelastin chaperone, EBP.

Fathers’ Experience of Parenting a Child With Juvenile Rheumatoid Arthritis

Abstract: The author examined the experience of fathers who have a child with juvenile rheumatoid arthritis (JRA). He used grounded theory methodology, in which 22 fathers participated in semistructured interviews, and developed a substantive theory of fathers' experience that addresses the impact of their child's JRA, their adaptational responses, and the meanings they associated with their experiences. Fathers were profoundly affected, perceived their child's condition as a catalyst for meaningful involvement, experienced many emotions, and sought to adopt a positive approach to making sense of their child's condition. Fathers' efforts to be strong for others resulted in an overreliance on self-support strategies, particularly during periods of high stress. Given the nature of fathers' experience and the extent of their involvement, greater attention by health care practitioners to fathers' adaptation is indicated.

Presentation and course of Type 2 diabetes in youth in a large multi-ethnic city.

Abstract: Aim To review the clinical experience of children and teens diagnosed with Type 2 diabetes (T2DM) at a paediatric hospital serving a large urban multi-ethnic population. Methods Retrospective chart review of patients with T2DM followed in the diabetes clinic at the Hospital for Sick Children (HSC) over an 8-year period. Patients who were included were younger than 18, referred at the onset of diabetes, and where presentation and/or clinical course was ‘typical’ of T2DM. Results Of 1020 children with diabetes followed at HSC, 4% were identified as having T2DM in 2002. There was a sixfold increase in new cases from 1994 to 2002. The mean age at diagnosis was 13.5 ± 2.2 years (range 8.8–17.5) with a female-to-male ratio of 1.7. Most had a first- or second-degree relative with T2DM. There was an overrepresentation of children with T2DM from Asian and African Canadian ethnic groups relative to the regional population. The majority of teens were asymptomatic at presentation, with a smaller number in diabetic ketoacidosis (DKA) at diagnosis. Mean HbA1c at diagnosis was 10 ± 3.4%. Approximately one half of patients were initially treated by diet and exercise with many requiring intensification of therapy over a short period of time. Conclusions We report a similar increase in T2DM incidence and clinical presentation at HSC to other clinic reports in large North American urban centres. Of note is the high prevalence of children of South/South-East Asian descent.

Making a difference in bullying: evaluation of a systemic school-based programme in Canada

Abstract: Impetus for the intervention study, early stages of planning, and funding Over the past decade, Canadians have become increasingly aware of the extent and consequences of bullying problems. Recently, there have been several high-profile cases of Canadian children who have suffered from prolonged victimisation, with severe consequences of suicide, revenge attacks, or death at the hands of peers. These cases have highlighted the need for empirically based prevention and intervention programmes. We will describe a school-based intervention programme developed prior to the recent surge in interest in the problem of bullying in Canada. This anti-bullying initiative emerged from a survey conducted in the early 1990s by the Toronto Board of Education in collaboration with researchers from York University. The questionnaire used for the survey was modelled after the Olweus self-report questionnaire (Olweus, 1989), with some adaptations for the Canadian context. The survey indicated that bullying and victimisation were pervasive problems. During the past two months, 24% of the grade 3–8 students reported that they had bullied other students at least once or twice, and 15% more than once or twice. Half of the students (49%) indicated that they had been victims of bullying at least once, 20% more than once or twice, and 8% reported being victimised weekly or more often during the past two months (Charach, Pepler, and Ziegler, 1995).

Primary Subcutaneous Primitive Neuroectodermal Tumor with Aggressive Behavior and an Unusual Karyotype: Case Report

Abstract: Primitive neuroectodermal tumor/Ewing sarcoma (PNET/ES) rarely occurs in the skin and subcutaneous tissues. We present a case of a 16-year-old girl with primary cutaneous and subcutaneous PNET/ES of the abdominal wall. Despite wide local excision and chemotherapy, she rapidly developed cranial bone and brain metastases, followed by lung and skeletal metastases, and died shortly thereafter. The recurrent tumor exhibited light microscopic features of a small, round, blue cell tumor with intracytoplasmic glycogen. Immunohistochemical analysis showed positivity for CD99, CD56, S100, and glial fibrillary acid protein, and ultrastructural features included cytoplasmic glycogen and focal complex interdigitating synaptic junction-like cytoplasmic folds. Cytogenetic analysis of the relapsed tumor showed a complex karyotype: 47,XX,i(1)(q10), der(4)t(4;19) (q33 approximately q35;q13.1), + 8,t(15;17)(q24;p11.2 approximately p12),der(19)t (19;20)(q13.1;p11.2),der(22)t(20;22)(q13;q13). Cytogenetic, interphase fluorescence in situ hybridization, and molecular genetic analyses failed to show t(11:22) (q24;q12) or abnormalities of chromosome region 22q12. The clinical behavior and atypical and complex cytogenetic abnormalities exhibited by the tumor in this patient are unusual and represent the most aggressive end of the clinical spectrum of cutaneous and subcutaneous PNET/ES.

Choroid plexus carcinomas in children: MRI features and patient outcomes

Abstract: Choroid plexus carcinomas (CPC) are rare malignant intracranial neoplasms usually occurring in young children. The objectives of this study were to characterize the preoperative MRI features of CPC, determine the frequency of disseminated disease in the CNS at diagnosis, and assess patient outcomes. The preoperative cranial MR images of 11 patients with CPC were retrospectively reviewed for lesion location, lesion size, un-enhanced and enhanced MRI signal characteristics, and presence of disseminated intracranial tumor. Postoperative cranial and spinal MRI images were reviewed for residual, recurrent, and/or disseminated tumor. The study group included six male and five female patients ranging in age from 5 months to 5.3 years (median=1.8 years). CPC were located in the lateral (n=8), fourth (n=1), and third (n=1) ventricles, and foramen of Luschka (n=1). Mean tumor size was 5.2cm×4.9cm×5.0 cm. On short-TR images, CPC had heterogeneous, predominantly intermediate signal with foci of high signal in 45% of lesions from areas of hemorrhage. On long-TR/long-TE images, solid portions of CPC typically had heterogeneous, intermediate-to-slightly-high signal. Small zones of low signal on long-TR/long-TE images were seen in 55% of the lesions secondary to areas of hemorrhage and/or calcifications. Tubular flow voids representing blood vessels were seen in 55% of the lesions. Zones of high signal comparable to CSF were seen in 64% of CPC secondary to cystic/necrotic zones. All CPC showed prominent contrast enhancement. Irregular enhancing margins suggesting subependymal invasion were seen in 73% of the lesions. Findings consistent with edema in the brain adjacent to the enhancing lesions were seen in 73% of CPC. CPC caused hydrocephalus in 82% of patients at diagnosis. Two patients died from hemorrhagic complications from surgical biopsies. Disseminated tumor in the leptomeninges was present in 45% of patients at diagnosis and was associated with a poor prognosis. The 1-year and 5-year survival probabilities were 55% and 45%, respectively. In conclusion, MRI features commonly associated with CPC include large intraventricular lesions with irregular enhancing margins; heterogeneous signal on long TR/long TE images and short-TR images; edema in adjacent brain; hydrocephalus; and presence of disseminated tumor. MRI evidence of disseminated tumor at diagnosis is associated with a poor prognosis.

Severe acute respiratory syndrome (SARS): chest radiographic features in children

Abstract: Severe acute respiratory syndrome (SARS) is a recently recognized condition of viral origin associated with substantial morbidity and mortality rates in adults. Little information is available on its radiologic manifestations in children. The goal of this study was to characterize the radiographic presentation of children with SARS. We abstracted data (n=62) on the radiologic appearance and course of SARS in pediatric patients with suspect (n=25) or probable (n=37) SARS, diagnosed in five hospital sites located in three cities: Toronto, Singapore, and Hong Kong. Available chest radiographs and thoracic CTs were reviewed for the presence of the following radiographic findings: airspace disease, air bronchograms, airways inflammation and peribronchial thickening, interstitial disease, pleural effusion, and hilar adenopathy. A total of 62 patients (suspect=25, probable=37) were evaluated for SARS. Patient ages ranged from 5.5 months to 17 years and 11.5 months (average, 6 years and 10 months) with a female-to-male ratio of 32:30. Forty-one patients (66.1%) were in close contact with other probable, suspect, or quarantined cases; 10 patients (16.1%) had recently traveled to WHO-designated affected areas within 10 days; and 7 patients (11.2%) were transferred from other hospitals that had SARS patients. Three patients, who did not have close/hospital contact or travel history to affected areas, were classified as SARS cases based on their clinical signs and symptoms and on the fact that they were living in an endemic area. The most prominent clinical presentations were fever, with a temperature over 38 °C (100%), cough (62.9%), rhinorrhea (22.6%), myalgia (17.7%), chills (14.5%), and headache (11.3%). Other findings included sore throat (9.7%), gastrointestinal symptoms (9.7%), rigor (8.1%), and lethargy (6.5%). In general, fever and cough were the most common clinical presentations amongst younger pediatric SARS cases (age<10 years), whereas, in addition to these symptoms, headache, myalgia, sore throat, chills, and/or rigor were common in older patients (age≥10 years). The chest radiographs of 35.5% of patients were normal. The most prominent radiological findings that were observed in the remaining patients were areas of consolidation (45.2%), often peripheral with multifocal lesions in 22.6%. Peribronchial thickening was noted on chest radiographs of 14.5% of patients. Pleural effusion was observed only in one patient (age 17 years and 11.5 months), whereas interstitial disease was not observed in any patient. In pediatric cases, SARS manifests with nonspecific radiographic features making radiological differentiation difficult, especially from other commonly encountered childhood respiratory viral illnesses causing airspace disease. The radiographic presentation of suspected SARS cases ranged from normal to mild perihilar peribronchial thickening. The radiographic presentations, as expected, were relatively more pronounced in the SARS probable cases.

c-kit Expression and Mutational Analysis in Medulloblastoma

Abstract: The proto-oncogene c-kit is a receptor tyrosine kinase recognized to initiate essential signal transduction pathways that transmit biological signals for cellular proliferation, differentiation, and metastasis. Aberrant expression or mutation of c-kit has been shown to be involved in the pathogenesis of many cancers. Studies using imatinib mesylate (STI 571, Gleevec, Novartis, East Hannover, NJ, USA), an inhibitor of the tyrosine kinases brc-abl, c-kit, and PDGFR, have shown significant response in patients with chronic myelogenous leukemia and gastrointestinal stromal tumor. With the aim of identifying additional groups of tumors that may use the stem cell factor/c-kit pathway and, secondarily, may be responsive to imatinib mesylate treatment, we looked at the expression of c-kit in medulloblastoma. Medulloblastoma, a highly invasive primitive neuroectodermal tumor of the cerebellum, is the most common, malignant central nervous system tumor of childhood. Histologic features of medulloblastoma have failed to provide an accurate prediction of the clinical-biological behavior of these tumors. Characterizing the genetic events that play a role in the biology of these tumors may allow for molecular sub-typing and could lead to the development of novel therapeutic strategies. This study evaluated c-kit expression and mutational status in 10 medulloblastoma tumor samples. All 10 medulloblastoma tumors expressed c-kit by reverse transcriptase-polymerase chain reaction and 9 by immunohistochemical analysis. All tumor samples were screened for mutations in exons 9, 11, and 13 of the c-kit gene by direct sequencing. No sequence abnormalities were detected in these exons. These experiments lead us to the conclusion that c-kit activation in medulloblastoma is independent of mutation.

When breastfeeding mothers need CNS-acting drugs.

Abstract: Background Breastfeeding is the ideal method of infant nutrition. However, if mothers need medications such as the central nervous system (CNS) acting drugs, infant safety concerns arise. Summarized information on infant exposure levels to drugs in milk and associated side effect profiles will help clinicians to rationalize and justify important drug therapy for a breastfeeding patient. Methods Electronic searches of MEDLINE and PsycINFO from 1966-2003, and of EMBASE from 1980-2003, were conducted for studies on breastfeeding or breast milk and medications in the following categories: antidepressants, antipsychotics, antiepileptics (or anticonvulsants) and anxiolytics. The infant exposure level (%) was defined as follows: [Drug concentration in milk (mg/mL)] x [Daily milk intake (mL/kg/d)] x 100 / Maternal dose (mg/kg/d). Results A total of 129 papers were eligible for analyses. Our findings indicate that the majority of the CNS-acting drugs, if taken by nursing women, result in average exposure levels to their breast-fed infants of less than 10% of the therapeutic doses per kg body weight. Exceptions are lithium, ethosuximide, phenobarbital, primidone, lamotrigine and topiramate. Adverse effect profiles do not always correlate with a higher exposure level. Overall, most reported adverse effect profiles appear benign. Where adverse effects were reported, they were often confounded by intrauterine exposure. Conclusions CNS-acting drugs taken by the mother do not appear to pose any major risks of immediate adverse effects to the breastfeeding infant, although with most of the newer drugs further research is needed to be conclusive.

Helicobacter pylori infection and gastric cancer: host, bug, environment, or all three?

Abstract: Helicobacter pylori is a common bacterial pathogen that colonizes the gastric mucosa of over 50% of the world’s population. All infected individuals exhibit chronic gastric inflammation, and approximately 1% of patients develop gastric cancers, including adenocarcinomas and mucosal-associated lymphoid tissue lymphomas. In 1994, the World Health Organization International Agency for Research on Cancer classified H. pylori as a type I, or definite carcinogen. Because the prevalence of gastric cancers among H. pyloriinfected patients varies between individuals, countries, and geographic areas, H. pylori disease-related outcomes are believed to be determined by an interplay between host factors, bacterial factors, and their interaction with the environment. This review highlights recent advances in our knowledge on H. pylori disease pathogenesis, focusing on the role of the host, bacteria, and environment in the development of gastric carcinoma.

Deformation Based Representation of Groupwise Average and Variability

Abstract: This paper presents a novel method for creating an unbiased and geometrically centered average from a group of images. The morphological variability of the group is modeled as a set of deformation fields which encode differences between the group average and individual members. We demonstrate the algorithm on a group of 27 MR images of mouse brains. The average image is highly resolved as a result of excellent groupwise registration. Local and global groupwise variability estimates are discussed.

Hepatic and colonic perforation by an abandoned ventriculoperitoneal shunt.

Abstract: We report a case of an abandoned distal limb of a ventriculoperitoneal shunt that resulted in hepatic as well as colonic perforation in a 12-year-old girl Although it is common practice at the time of shunt revision to leave a retained distal catheter in the peritoneal cavity, we suggest this can result in perforation of solid as well as hollow viscera

Early Doppler changes in a renal transplant patient secondary to abdominal compartment syndrome.

Abstract: Physiologic changes in renal transplant patients, such as transiently low central venous pressure, may be related to increased intra-abdominal pressure, from the volume of the transplanted kidney itself. Using intraoperative and postoperative Doppler ultrasound of the transplant renal vessels, we identified changes in flow dynamics following closure of the abdomen and reversal of the changes when the abdomen was reopened. This was attributed to abdominal compartment syndrome and a fasciotomy was created in the abdominal wall to accommodate the transplanted kidney. The findings in this case, in keeping with abdominal compartment syndrome, are not often considered in transplant recipients, but may explain some of the postsurgical physiology in some patients, particularly in the pediatric population.