The association of venous thromboembolism with survival in pediatric cancer patients: a population-based cohort study

Venous thromboembolism (VTE) is a well-recognized complication in pediatric oncology patients. Studies in adult oncology patients have suggested a potential negative association between VTE and survival, but this association has not been examined in pediatric patients yet. The aim of this study was to assess the association of VTE with survival in pediatric oncology patients. Data from all pediatric oncology patients treated at the two tertiary care centers in Atlantic Canada were pooled to create a population-based cohort. The association between VTE and survival was analyzed using a Cox proportional hazards model stratified by diagnosis group (leukemia, lymphoma, and other; sarcoma) and adjusted for age at diagnosis and sex. Out of 939 patients included in this study, 73 had a VTE (8%) and 131 (14%) patients died during the study period. Children in the leukemia/lymphoma/other group with a VTE had significantly poorer survival relative to children in the same group who did not have a VTE. Although children with sarcoma and VTE had poorer survival compared to children with sarcoma with no VTE, this association was not statistically significant. In this population-based study, we found a negative association between VTE and survival in pediatric oncology patients. If future studies confirm this association, this finding may have prognostic implications and potentially offer new avenues for the management of pediatric patients with cancer.     

Echocardiographic diagnosis of congential absence of the pericardium in a patient with VATER association defects

The VATER association denotes a nonrandom pattern of congential malformations which typically include vertebral defects, anal atresia, tracheo-esophageal fistula, and radial and renal dysplasia. Vascular anomalies including ventricular septal defect and single umbilical artery have also been described, although the frequency of cardiovascular anomalies in this congenital association is unknown. In this report, we describe a 26-year-old patient with several VATER association defects who, in addition, was found to have congenital absence of the left pericardium and an aberrant right subclavian artery.     

Auto-immune haemolytic anaemia and Crohn's disease: a case report and review of the literature

The association between ulcerative colitis and auto-immune haemolytic anaemia is well described. However, only two cases of auto-immune haemolytic anaemia occurring in association with Crohn's disease have been described in the literature. We report on a third case and discuss the importance of diagnosis and the therapeutic implications of this association.     

New gene associations in osteoarthritis: what do they provide, and where are we going?

PURPOSE OF REVIEW: Osteoarthritis is a serious medical, social and economic problem affecting populations worldwide. Identifying susceptibility genes for osteoarthritis is a critical step in tackling this disease. The association study is today's most powerful tool for finding such genes, and the osteoarthritis research community has enjoyed initial success through the identification of several promising candidates. This review summarizes recent advances and emerging challenges in osteoarthritis association studies. RECENT FINDINGS: Replication studies have confirmed association of functional sequence variations in the secreted frizzled-related protein 3 (FRZB) and asporin (ASPN) genes with osteoarthritis. These studies have also prompted discussion of population-specific differences in reported associations. Association of several other promising genes with osteoarthritis, including LRCH1, RHOB, TXNDC3 and GDF5, await replication. The Human Genome Project and the International HapMap Project have established an infrastructure to support genome-wide association studies. Large-scale case-control association scans are underway, and genome-wide association scans are also beginning. SUMMARY: Due to initial success in confirming several susceptibility genes and the advent of the post-genome sequence era, this area of osteoarthritis study is expanding quickly. To overcome current challenges and to move on to the next stage, however, international collaboration based on a common platform is essential.     

What Ancestry Can Tell Us About the Genetic Origins of Inter-Ethnic Differences in Asthma Expression

Differences in asthma prevalence have been described across different populations, suggesting that genetic ancestry can play an important role in this disease. In fact, several studies have demonstrated an association between African ancestry with increased asthma susceptibility and severity, higher immunoglobulin E levels, and lower lung function. In contrast, Native American ancestry has been shown to have a protective role for this disease. Genome-wide association studies have allowed the identification of population-specific genetic variants with varying allele frequency among populations. Additionally, the correlation of genetic ancestry at the chromosomal level with asthma and related traits by means of admixture mapping has revealed regions of the genome where ancestry is correlated with the disease. In this review, we discuss the evidence supporting the association of genetic ancestry with asthma susceptibility and asthma-related traits, and highlight the regions of the genome harboring ancestry-specific genetic risk factors.     

Pulmonary giant bulla in Wegener's granulomatosis

The association of lung emphysema with severe systemic antineutrophil cytoplasm antibodies (ANCA)-positive vasculitis, such as Wegener's granulomatosis is unusual since only four cases have been described previously. We report the first case of a 30 year-old smoker man presenting with biopsy-proven Wegener's granulomatosis, who developed a bullous emphysema during severe active lung vasculitis, in association with positive ANCA disclosing an anti-myeloperoxydase pattern. Alpha 1-antitrypsin deficiency, a known risk factor of lung emphysema recently found to be associated with anti-proteinase 3-positive vasculitis, was not present in this patient. Cigarette smoking, in association with severe lung vasculitis, might have contributed to the development of this emphysematous lesion.     

Association of coeliac disease and inflammatory bowel disease.

The association of coeliac disease and inflammatory bowel disease is rare, as only three individual cases have been reported. Four additional cases of the association are described. A review of the prevalence figures for the two disorders suggests that this is more than a chance association.     

Design and Interpretation of Linkage and Association Studies on Osteoporosis

Osteoporosis is a common disease with strong genetic control. Genetic linkage and association studies are the two most popular methods used to investigate the genetic basis of osteoporosis. Linkage studies have been successfully used to identify quantitative trait loci (QTLs), and association studies have been widely performed to test candidate genes for osteoporosis. In this article, we review the design and interpretation of linkage and association studies on osteoporosis.     

Association studies of genetic polymorphisms in central obesity: a critical review

During the past decade, mutations affecting liability to central obesity have been discovered at a phenomenal rate, and despite few consistently replicated findings, a number of intriguing results have emerged in the literature. Association studies have been proposed to identify the genetic determinants of complex traits such as central obesity. The advantages of the association method include its relative robustness to genetic heterogeneity and the ability to detect much smaller effect sizes than is detectable using feasible sample sizes in linkage studies. However, the current literature linking central obesity to genetic variants is teeming with reports of associations that either cannot be replicated or for which corroboration by linkage has been impossible to find. Explanations for this lack of reproducibility are well rehearsed, and typically include poor study design, incorrect assumptions about the underlying genetic architecture, and simple overinterpretation of data. These limitations create concern about the validity of association studies and cause problems in establishing robust criteria for undertaking association studies. In this article, the current status of the literature of association studies for genetic dissection of central obesity is critically reviewed.     

Overweight and constipation in adolescents

Background  

The association between overweight and gastrointestinal symptoms has been recently studied in the literature; however, few studies have evaluated the association between overweight and constipation in adolescents in a community-based sample. The aim of this study was to analyze the prevalence of constipation and its association with being overweight in a community-based survey with adolescents.     

Psoriasis and systemic lupus erythematosus: a rare association with specific therapeutic problems

The association psoriasis and systemic lupus erythematosus (SLE) is a very uncommon association. We report three cases, diagnosed in an Internal Medicine department between 1993 and 2000. Few cases of psoriasis/SLE have been published in the literature. Psoriasis generally precedes the diagnosis of SLE. Psoriasis can also be associated with discoid lupus erythematosus. In some cases, SLE appears as a complication of ultraviolet phototherapy indicated for the psoriasis. The association psoriasis/SLE does not seem to have distinctive immunologic features. Specific therapeutic difficulties may occur. Indeed, hydroxychloroquine may exacerbate the psoriasis. Systemic use of corticosteroids raises the risk of severe psoriasis relapse during withdrawal. In addition, the diagnosis of psoriasic arthropathy is more difficult in this setting. The psoriasis/SLE association might be a good indication for using methotrexate.     

The effect of in-utero undernutrition on the insulin resistance syndrome

The metabolic and cardiovascular complications associated with in-utero undernutrition have been identified during the past 10 years. Reduced fetal growth is independently associated with an increased risk for the development of cardiovascular diseases, the insulin resistance syndrome and its components: hypertension, dyslipidemia, impaired glucose tolerance, and type 2 diabetes. All appear to result from the initial development of insulin resistance that seems to be a key component underlying this association. Several hypotheses have been proposed over the past 10 years to understand this unexpected association. Each of them points to either a detrimental fetal environment or genetic susceptibilities or interactions between these two components as playing a critical role in this context. The hypothesis that this association could be the consequence of genetic/environmental interactions remains at the moment the most attractive. Although the mechanism remains unclear, there is also some evidence that adipose tissue plays a role in the emergence of insulin resistance associated with in-utero undernutrition.     

Genetic determinants of hypertension: An update

Hypertension represents a global public health burden. In addition to the rarer Mendelian forms of hypertension, classic genetic studies have documented a significant heritable component to the most common form, essential hypertension (EH). Extensive efforts are under way to elucidate the genetic basis of this disease. Recently, a new form of Mendelian hypertension has been identified, pharmacogenetic association studies in hypertensive patients have identified novel gene-by-drug interactions, and the first genome-wide association studies of EH have been published. New findings in consomic and congenic rat models also offer new clues to the genetic architecture of this complex phenotype. In this review, the authors summarize and evaluate the most recent findings related to hypertension gene identification.     

Education and psychological distress among older Chinese

OBJECTIVE: The goal of this research is to see if more highly educated older Chinese have lower levels of distress than do their poorly educated counterparts and whether engaging in cognitively stimulating activities such as reading and playing mahjong explains the association. METHOD: Using the Chinese Healthy Longevity Survey, the authors find a significant negative association between education and psychological distress. Much of the association is mediated by activities, but not all in the ways expected. Reading, playing mahjong, and watching television all negatively correlate with distress. DISCUSSION: Better-educated older Chinese have lower levels of distress than do their less-well-educated counterparts in part because they engage in cognitively stimulating activities, have better economic circumstances, and engage in more physical activity.     

Angiotensin I-converting enzyme gene polymorphism in two ethnic groups living in Brazil's southern region: association with age

BACKGROUND: Several studies have been published on the association between ACE (angiotensin I-converting enzyme) polymorphism and longevity. However, the results are controversial. METHODS: We analyzed the association between ACE polymorphism and age in two different ethnic populations: a population originating from different European countries (Gaucha Population, GP) and a population originating from Japan (JP). Both populations live in Brazil's southern region. RESULTS: We determined the ACE genotype in 834 persons aged 10-104 years. The ACE genotype and allele frequencies differed between the two populations, with the D allele being more frequent in GP than JP. We found an association between the DD genotype and D allele and age in the GP group only. The ACE polymorphism-age association occurred at age >60 years in the GP population with decreasing II frequency. CONCLUSION: We cannot dismiss the possibility of the association between ACE polymorphism and age involving linkage disequilibrium, since the nature of this phenomenon is still controversial. From our studies, it appears that there is a correlation between age, ethnicity, and ACE polymorphism. More of such studies are warranted, as further investigation in this area will have a high clinical relevance to cardiovascular disease and aging research.     

Neighbourhood social capital and obesity: a systematic review of the literature

Social capital, defined as the resources accessed by individuals and groups through social connections, has been posited to be a social determinant of obesity. However, empirical evidence for this association has been inconsistent – namely, some studies have found a protective association while others have reported no correlation. We sought to conduct a systematic review on the relation between neighbourhood social capital and obesity, considering potential differences on the results based on the measures used and the covariates and mediators included in the studies. PRISMA statement guidelines were followed. Our results indicate that an association between neighbourhood social capital and obesity exists, but that it depends on the measures and covariates used in the study design. Understanding the role of social capital in the development and/or maintenance of obesity will require the use of strong methodological designs and a thorough conceptualization of how this relationship may arise.     

Rhinite allergique chez l’enfant

Allergic rhinitis has for a long time been considered to be a relatively minor allergic symptom, much less important than anaphylaxis and asthma. Its true frequency was unknown. Its management remained empiric. Its association with asthma was not clearly determined, although concerning adults, this association was rather well-known. A number of studies in children have now made more certain the association between asthma and allergic rhinitis, the impact of rhinitis on the child's quality of life, and the significance of allergic rhinitis in the natural history of allergy and asthma. This review will cover some current aspects of allergic rhinitis: its association with asthma and food allergy, quantification of atopy, and its impact on daily life. It leads to recommendations for everyday practice of allergy in pediatrics. Given that allergic rhinitis probably begins earlier and earlier, children with this condition need to be followed closely and, if necessary, have their allergy tests repeated. Specific immunotherapy certainly merits to be used more frequently.     

Genetic epidemiology of rheumatoid arthritis

PURPOSE OF REVIEW: This review aims to summarize articles published between October 2004 and November 2005 that have investigated the genetic epidemiology of rheumatoid arthritis. RECENT FINDINGS: The consistent replication of an association between the R620W single nucleotide polymorphism in PTPN22 and rheumatoid arthritis clearly establishes this polymorphism as an important risk factor for rheumatoid arthritis. SUMMARY: Genetic investigations of rheumatoid arthritis have predominantly been single nucleotide polymorphism-based candidate gene association studies searching for markers of susceptibility, severity or treatment response. Studies of the human leukocyte antigen region have refined and added to our understanding of the complex associations to polymorphisms with this locus. PTPN22 has emerged strongly as a genuine rheumatoid arthritis susceptibility gene with replications of the association to the R620W single nucleotide polymorphism. Many investigations have been conducted on the genetics of treatment response -- some 'generic' and others specific in terms of identifying genetic influences to the mode of action and metabolism of particular agents.     

TAP1 alleles in insulin-dependent diabetes mellitus: a newly defined centromeric boundary of disease susceptibility.

It has been previously demonstrated that individuals with certain DR alleles have an increased relative risk of developing insulin-dependent diabetes mellitus (IDDM). The disease association is even stronger with certain DQ alleles but there is little association with DP providing a boundary of disease association to the 430 kb between DQ and DP. The recently described TAP (transporter associated with antigen processing) genes have been mapped approximately midway between DP and DQ. Therefore, it was of interest to determine if any TAP alleles were associated with IDDM. In addition to the alleles of TAP1 that have been described, others were identified during this study. Diabetics and normal controls were screened for TAP1 using single-stranded conformational polymorphism and relative risk was determined. In the same population group we have studied extensively in the past, we found a higher association of a TAP1 allele with IDDM than with any single HLA-DP allele but the risk was lower than with HLA-DQB1*0302. These data provide new limits for IDDM susceptibility to the 190-kb interval between TAP1 and HLA-DQB1.     

Patent Foramen Ovale and Stroke: Should PFOs Be Closed in Otherwise Cryptogenic Stroke?

Since initial reports of its association with ischemic stroke appeared in 1988, there has been continued controversy regarding the existence and strength of the association between patent foramen ovale (PFO) and ischemic stroke. Many case-control studies have reported an association between incident cryptogenic ischemic stroke and PFO, yet population-based studies have failed to confirm this association. Studies of the risk of recurrent stroke in patients with cryptogenic stroke with or without PFO have not shown an increased risk of recurrent stroke in patients with PFO. Meanwhile, use of devices to close PFOs and atrial septal defects percutaneously has increased dramatically since their introduction. Completion of the randomized clinical trials of PFO closure currently in progress is vital to determine if the benefits of PFO closure in cryptogenic stroke outweigh its risks.