Unchanged incidence and increased survival in children with neuroblastoma in Denmark 1981–2000: a population-based study

Treatment results for neuroblastoma in Denmark have been poorer than in other Nordic countries, so we investigated whether a change in incidence, stage distribution and survival had occurred between 1981 and 2000. Clinical data were retrieved from the medical charts of 160 children <15 years of age with extra-cranial neuroblastoma (n=139) or ganglioneuroblastoma (n=21) diagnosed in Denmark between 1981 and 2000. The minimal follow-up time was 52 months. Statistical analyses were performed in STATA. The incidence was 8.55 per million children below 15 years of age (world standard 9.6) and 42.6 per million children below 12 months of age, and it has remained unchanged since 1970. The median age at diagnosis was 27 months. In all, 32% of the children were aged below 12 months at diagnosis, 53% had metastatic disease and in 12% the diagnosis was made incidentally. Prognostic factors such as age, stage and site of primary tumour were the same as in other studies and did not change. During the study period, the mortality rate decreased steadily, and the 5-year survival rate increased from 38% in 1981–1985 to 59% in 1996–2000, corresponding to the level found in other Western countries. Increased survival was also seen in children with metastatic disease. Participation in international studies, better supportive care and possibly postoperative autologous stem cell transplantation may have contributed to the increased survival

Pretreatment 18F-FAZA PET Predicts Success of Hypoxia-Directed Radiochemotherapy Using Tirapazamine

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Non-classical ProIL-1beta activation during mammary gland infection is pathogen-dependent but caspase-1 independent

Infection of the mammary gland with live bacteria elicits a pathogen-specific host inflammatory response. To study these host-pathogen interactions wild type mice, NF-kappaB reporter mice as well as caspase-1 and IL-1beta knockout mice were intramammarily challenged with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The murine mastitis model allowed to compare the kinetics of the induced cytokine protein profiles and their underlying pathways. In vivo and ex vivo imaging showed that E. coli rapidly induced NF-kappaB inflammatory signaling concomitant with high mammary levels of TNF-alpha, IL-1 alpha and MCP-1 as determined by multiplex analysis. In contrast, an equal number of S. aureus bacteria induced a low NF-kappaB activity concomitant with high mammary levels of the classical IL-1beta fragment. These quantitative and qualitative differences in local inflammatory mediators resulted in an earlier neutrophil influx and in a more extensive alveolar damage post-infection with E. coli compared to S. aureus. Western blot analysis revealed that the inactive proIL-1beta precursor was processed into pathogen-specific IL-1beta fragmentation patterns as confirmed with IL-1beta knockout animals. Additionally, caspase-1 knockout animals allowed to investigate whether IL-1beta maturation depended on the conventional inflammasome pathway. The lack of caspase-1 did not prevent extensive proIL-1beta fragmentation by either of S. aureus or E. coli. These non-classical IL-1beta patterns were likely caused by different proteases and suggest a sentinel function of IL-1beta during mammary gland infection. Thus, a key signaling nodule can be defined in the differential host innate immune defense upon E. coli versus S. aureus mammary gland infection, which is independent of caspase-1

Guidelines; from foe to friend? Comparative interviews with GPs in Norway and Denmark

<p>Abstract</p> <p>Background</p> <p>GPs follow clinical guidelines to varying degrees across practices, regions and countries, but a review study of GPs' attitudes to guidelines found no systematic variation in attitudes between studies from different countries. However, earlier qualitative studies on this topic are not necessarily comparable. Hence, there is a lack of empirical comparative studies of GP's attitudes to following clinical guidelines. In this study we reproduce a Norwegian focus group study of GPs' general attitudes to national clinical guidelines in Denmark and conduct a comparative analysis of the findings.</p> <p>Methods</p> <p>A strategic sample of GP's in Norway (27 GPs) and Denmark (18 GPs) was interviewed about their attitudes to guidelines, and the interviews coded and compared for common themes and differences.</p> <p>Results</p> <p>Similarities dominated the comparative material, but the analysis also revealed notable differences in attitudes between Norwegian and the Danish GPs. The most important difference was related to GP's attitudes to clinical guidelines that incorporated economic evaluations. While the Norwegian GPs were sceptical to guidelines that incorporated economic evaluation, the Danish GPs regarded these guidelines as important and legitimate. We suggest that the differences could be explained by the history of guideline development in Norway and Denmark respectively. Whereas government guidelines for rationing services were only newly introduced in Norway, they have been used in Denmark for many years.</p> <p>Conclusion</p> <p>Comparative qualitative studies of GPs attitudes to clinical guidelines may reveal cross-national differences relating to the varying histories of guideline development. Further studies are needed to explore this hypothesis.</p

Long-Term Gynecological Outcomes in Women with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

Background. Our knowledge on long-term outcome in CAH remains incomplete. Methods. In a prospective study (33 CAH patients, 33 age-matched controls), reproductive outcomes, self-rating of genital appearance and function, and sexuality were correlated to degree of initial virilisation, genotype, and surgery. Results. Patients had larger median clitoral lengths (10.0 mm [range 2–30] versus 3.5 [2–8], P < .001), shorter vaginal length (121 mm [100–155] versus 128 [112–153], P = .12), lower uterine volumes (29.1 ml [7.5–56.7] versus 47.4 [15.9–177.5], P = .009), and higher ovarian volumes (4.4 ml [1.3–10.8] versus 2.8 [0.6–10.8], P = .09) than controls. Satisfaction with genital appearance was lower and negatively correlated to degree of initial virilisation (rs = ≤−0.39, P ≤ .05). More patients had never had intercourse (P = .001), and age at 1st intercourse was higher (18 yrs versus 16 yrs, P = .02). Conclusion. Despite overall acceptable cosmetic results, reproductive outcomes were suboptimal, supporting that multidisciplinary teams should be involved in adult follow up of CAH patients

MicroRNAs in cardiac arrhythmia: DNA sequence variation of MiR-1 and MiR-133A in long QT syndrome.

Long QT syndrome (LQTS) is a genetic cardiac condition associated with prolonged ventricular repolarization, primarily a result of perturbations in cardiac ion channels, which predisposes individuals to life-threatening arrhythmias. Using DNA screening and sequencing methods, over 700 different LQTS-causing mutations have been identified in 13 genes worldwide. Despite this, the genetic cause of 30-50% of LQTS is presently unknown. MicroRNAs (miRNAs) are small (∼ 22 nucleotides) noncoding RNAs which post-transcriptionally regulate gene expression by binding complementary sequences within messenger RNAs (mRNAs). The human genome encodes over 1800 miRNAs, which target about 60% of human genes. Consequently, miRNAs are likely to regulate many complex processes in the body, indeed aberrant expression of various miRNA species has been implicated in numerous disease states, including cardiovascular diseases. MiR-1 and MiR-133A are the most abundant miRNAs in the heart and have both been reported to regulate cardiac ion channels. We hypothesized that, as a consequence of their role in regulating cardiac ion channels, genetic variation in the genes which encode MiR-1 and MiR-133A might explain some cases of LQTS. Four miRNA genes (miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2), which encode MiR-1 and MiR-133A, were sequenced in 125 LQTS probands. No genetic variants were identified in miR-1-1 or miR-133a-1; but in miR-1-2 we identified a single substitution (n.100A> G) and in miR-133a-2 we identified two substitutions (n.-19G> A and n.98C> T). None of the variants affect the mature miRNA products. Our findings indicate that sequence variants of miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2 are not a cause of LQTS in this cohort