High frequency of low-level microsatellite instability in early colorectal cancer

Molecular events in early colorectal cancers (CRCs) have not been well elucidated because of the low incidence of early CRCs in clinical practice. Therefore, we studied 104 sporadic early CRCs with invasion limited to submucosa compared with 116 advanced CRCs. Loss of heterozygosity as well as microsatellite instability (MSI) status was examined. A significantly high frequency of low-level MSI (MSI-L) phenotype was detected in early CRCs (51.0%) compared with advanced CRCs (25.9%; P = 0.0001). In early and advanced CRCs, samples with MSI-L phenotype differed from microsatellite stable (MSS) phenotype with respect to loss of heterozygosity at 1p32 and 8p12-22. MSI-L is a frequent genetic event in early CRCs and may be a novel pathway in colorectal carcinogenesis distinct from both MSI-H and MSS.

The Relative Frequency of the Synthetic End Composite Futures in the Newspaper Quest-France and some Observations on Distribution

Figures on the relative frequency of synthetic and composite future forms in Ouest-France are presented and compared with those of earlier studies on the passé simple and passé composé. The synthetic future is found to be dominant. Possible formal explanations for distribution are found to be inconclusive. Distribution across different text-types is found to be more promising, since contrastive functions of the two forms can be identified in texts where they co-occur. The composite future typically reports new proposals or plans as current news, while the synthetic future outlines details that will be realised at the time of implementation. Both functions are important in dailies, but current news is more often expressed in the present tense at the expense of the composite future.

High frequency of BRAF mutations in nevi

To evaluate the timing of mutations in BRAF (v-raf murine sarcoma viral oncogene homolog B1) during melanocytic neoplasia, we carried out mutation analysis on microdissected melanoma and nevi samples. We observed mutations resulting in the V599E amino-acid substitution in 41 of 60 (68%) melanoma metastases, 4 of 5 (80%) primary melanomas and, unexpectedly, in 63 of 77 (82%) nevi. These data suggest that mutational activation of the RAS/RAF/MAPK pathway in nevi is a critical step in the initiation of melanocytic neoplasia but alone is insufficient for melanoma tumorigenesis.

Differences in lung function, growth parameters and frequency of hospital admissions between adolescents with cystic fibrosis-related diabetes and controls

As survival of patients with CF increases,glucose intolerance and cystic fibrosisrelated diabetes (CFRD),ar e increasingly recognised common complications. CFRD may be preceded by a pre-diabetic state. Using markers identified as being associated with CFRD may improve targeted screening. Aim: To identify features consistently predicting CFRD in paediatric patients. Patients diagnosed with CFRD between January 1997–January 2002 were compared with age and sex matched controls. Clinical,micr obiological, and hospitalisation data was collected at time of CFRD diagnosis,and at six monthly intervals for 3 yr prior to diagnosis. Eight patients with CFRD were identified,mean age 13.7 yr (S.D. 3.49) at time of diagnosis. Control patients underwent OGTT to ensure normal glucose tolerance. Patients with CFRD had a lower FEV1 up to 12 months prior to diagnosis however, this was only significant at diagnosis. There was no difference in weight and height z scores between the 2 groups; however,the decrease in weight and height z scores in the CFRD group over 3 yr prior to diagnosis was significant. Mean number of days in hospital and admissions per patient significantly increased in the CFRD group,6 months prior to diagnosis. No other significant differences were observed between the 2 groups. Conclusions: This study has shown a difference in lung function,gr owth parameters and frequency of hospital admissions between patients with CFRD and controls. These differences may be utilised as tools for targeted screening in the paediatricyadolescent population. Further larger scale studies are required to improve guidelines for targeted screening in this population.

Injury and frequency of use of playground equipment in public schools and parks in Brisbane, Australia

Objective: The purpose of this study was to determine the frequency of use of play equipment in public schools and parks in Brisbane, Australia, and to estimate an annual rate of injury per use of equipment, overall and for particular types of equipment. Methods: Injury data on all children injured from playground equipment and seeking medical attention at the emergency department of either of the two children's hospitals in the City of Brisbane were obtained for the years 1996 and 1997. Children were observed at play on five different pieces of play equipment in a random sample of 16 parks and 16 schools in the City of Brisbane. Children injured in the 16 parks and schools were counted, and rates of injury and use were calculated. Results: The ranked order for equipment use in the 16 schools was climbing equipment (3762 uses), horizontal ladders (2309 uses), and slides (856 uses). Each horizontal ladder was used 2.6 times more often than each piece of climbing equipment. Each horizontal ladder was used 7.8 times more than each piece of climbing equipment in the sample of public parks. Slides were used 4.6 times more than climbing equipment in parks and 1.2 times more in public schools. The annual injury rate for the 16 schools and 16 parks under observation was 0.59/100000 and 0.26/100000 uses of equipment, respectively. Conclusions: This study shows that annual number of injuries per standardized number of uses could be used to determine the relative risk of particular pieces of playground equipment. The low overall rate of injuries/100000 uses of equipment in this study suggests that the benefit of further reduction of injury in this community may be marginal and outweigh the economic costs in addition to reducing challenging play opportunities.

Increased mononuclear cell activation and apoptosis early after human liver transplantation is associated with a reduced frequency of acute rejection

Experimental models of orthotopic liver transplantation (OLT) have shown that the very early events post-OLT are critical in distinguishing immunogenic and tolerogenic reactions. In rodents, increased leukocyte apoptosis and cytokine expression have been demonstrated in tolerogenic strain combinations. Information from human OLT recipients is less abundant. The aim of this study was to determine the amount of early leukocyte activation and apoptosis following human OLT, and to correlate this with subsequent rejection status. Peripheral blood mononuclear cells (PBMC) were isolated from 76 patients undergoing OLT - on the day prior, 5 hrs after reperfusion (day 0), and 18-24 hrs post-OLT (day 1). The mean level of apoptotic PBMCs on post OLT day 1 was higher than healthy recipients (0.9% +/- 0.2 vs. 0.2% +/- 0.1, p = 0.013). Apoptosis was greater in nonrejecting (NR) (1.1% +/- 0.3) compared with acutely-rejecting (R) (0.3% +/- 0.1, p = 0.021) patients. On day 1, PBMC from NR patients had increased expression of IFN-gamma (p = 0.006), IL-10 (p = 0.016), and CD40 ligand (p = 0.02) compared with R. Donor cell chimerism on day 1 did not differ between the groups indicating that this was unlikely to account for increased PBMC apoptosis in the NR group. Interestingly, the level of chimerism on day 0 was significantly higher in NR (3.8% +/- 0.6) compared with R (1.2% +/- 0.4, p = 0.004) patients and there was a close correlation between chimerism on day 0 and cytokine expression on day 1. These results imply that similar mechanisms are occurring in the human liver to promote graft acceptance as in the experimental models of liver transplantation and suggest that strategies that promote liver transplant acceptance in rodents might be applicable to humans.

Effect of water depth and water velocity upon the surfacing frequency of the bimodally respiring freshwater turtle, Rheodytes leukops

This study examines the effect of increasing water depth and water velocity upon the surfacing behaviour of the bimodally respiring turtle, Rheodytes leukops. Surfacing frequency was recorded for R. leukops at varying water depths (50, 100, 150 cm) and water velocities (5, 15, 30 cm s(-1)) during independent trials to provide an indirect cost-benefit analysis of aquatic versus pulmonary respiration. With increasing water velocity, R. leukops decreased its surfacing frequency twentyfold, thus suggesting a heightened reliance upon aquatic gas exchange. An elevated reliance upon aquatic respiration, which presumably translates into a decreased air-breathing frequency, may be metabolically more efficient for R. leukops compared to the expenditure (i.e. time and energy) associated with air-breathing within fast-flowing riffle zones. Additionally, R. leukops at higher water velocities preferentially selected low-velocity microhabitats, presumably to avoid the metabolic expenditure associated with high water flow. Alternatively, increasing water depth had no effect upon the surfacing frequency of R. leukops, suggesting little to no change in the respiratory partitioning of the species across treatment settings. Routinely long dives (>90 min) recorded for R. leukops indicate a high reliance upon aquatic O-2 uptake regardless of water depth. Moreover, metabolic and temporal costs attributed to pulmonary gas exchange within a pool-like environment were likely minimal for R. leukops, irrespective of water depth.

Frequency of insomnia report in patients with obstructive sleep apnoea hypopnea syndrome (OSAHS)

Background and purpose: Insomnia and Obstructive Sleep Apnoea Hypopnea Syndrome (OSAHS) are the two most common sleep disorders, and both have significant associated health costs. Despite this, relatively little is known about the prevalence or impact of insomnia in those with OSAHS, although a recent study suggested there may be substantial comorbidity between these disorders [Chest 120 (2001) 1923-9]. The primary aim of this study was to further explore the prevalence of insomnia in OSAHS. A secondary aim was to assess the effect of factors that may impact on both conditions, including mood and sleep-beliefs. Patients and methods: Consecutive patients referred to an accredited Sleep Investigations Unit (n = 105) completed a brief standardized battery of validated questionnaires assessing sleep-related variables and mood. Results: Results showed a high rate of prevalence of clinical insomnia in this OSAHS population, and a strong positive correlation between OSAHS and insomnia symptom severity. Further, OSAHS patients with comorbid insomnia had increased levels of depression, anxiety and stress compared to patients with OSAHS-only, and both patient groups reported similar and significant levels of dysfunctional beliefs about sleep. Findings in relation to habitual sleep, assessed using subjective (diary) and objective criteria (polysomnogram), were mixed but generally showed greater sleep disturbance among those with OSAHS-insomnia compared to those with OSAHS-only. Conclusions: Overall these findings suggest that comorbidity of insomnia in OSAHS patients may lead to increased OSAHS severity and that patients with both conditions may experience more symptoms relating to depression, anxiety and stress. These findings underscore the need for insomnia assessment and management services, even in clinics that primarily service patients with OSAHS. (C) 2004 Elsevier B.V. All rights reserved.

Low frequency of CHEK2 1100delC allele in Australian multiple-case breast cancer families: functional analysis in heterozygous individuals

A protein-truncating variant of CHEK2, 1100delC, is associated with a moderate increase in breast cancer risk. We have determined the prevalence of this allele in index cases from 300 Australian multiple-case breast cancer families, 95% of which had been found to be negative for mutations in BRCA1 and BRCA2. Only two (0.6%) index cases heterozygous for the CHEK2 mutation were identified. All available relatives in these two families were genotyped, but there was no evidence of co-segregation between the CHEK2 variant and breast cancer. Lymphoblastoid cell lines established from a heterozygous carrier contained approximately 20% of the CHEK2 1100delC mRNA relative to wild-type CHEK2 transcript. However, no truncated CHK2 protein was detectable. Analyses of expression and phosphorylation of wild-type CHK2 suggest that the variant is likely to act by haploinsufficiency. Analysis of CDC25A degradation, a downstream target of CHK2, suggests that some compensation occurs to allow normal degradation of CDC25A. Such compensation of the 1100delC defect in CHEK2 might explain the rather low breast cancer risk associated with the CHEK2 variant, compared to that associated with truncating mutations in BRCA1 or BRCA2.

Rifampicin and sodium fusidate reduces the frequency of methicillin-resistant Staphylococcus aureus (MRSA) isolation in adults with cystic fibrosis and chronic MRSA infection

Nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) to patients with cystic fibrosis (CF) frequently results in chronic respiratory tract carriage. This is an increasing problem, adds to the burden of glycopeptide antibiotic use in hospitals, and represents a relative contraindication to lung transplantation. The aim of this study was to determine whether it is possible to eradicate MRSA with prolonged oral combination antibiotics, and whether this treatment is associated with improved clinical status. Adult CF patients (six mate, one female) with chronic MRSA infection were treated for six months with rifampicin and sodium fusidate. Outcome data were examined for six months before treatment, on treatment and after treatment. The patients had a mean age of 29.3 (standard deviation = 6.3) years and FEV1 of 36.1% (standard deviation = 12.7) predicted. The mean duration of MRSA isolation was 31 months. MRSA isolates identified in these patients was of the same lineage as the known endemic strain at the hospital when assessed by pulsed-field get electrophoresis. Five of the seven had no evidence of MRSA during and for at [east six months after rifampicin and sodium fusidate. The proportion of sputum samples positive for MRSA was lower during the six months of treatment (0.13) and after treatment (0.19) compared with before treatment (0.85) (P < 0.0001). There was a reduction in the number of days of intravenous antibiotics per six months with 20.3 +/- 17.6 on treatment compared with 50.7 before treatment and 33.0 after treatment (P = 0.02). There was no change in lung function. Gastrointestinal side effects occurred in three, but led to therapy cessation in only one patient. Despite the use of antibiotics with anti-staphylococcal activity for treatment of respiratory exacerbation, MRSA infection persists. MRSA can be eradicated from the sputum of patients with CF and chronic MRSA carriage by using rifampicin and sodium fusidate for six months. This finding was associated with a significant reduction in the duration of intravenous antibiotic treatment during therapy. (C) 2003 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.