Developing a national colorectal educational agenda: a survey of the Association of Coloproctology of Great Britain and Ireland.

AIM: In order to develop its education agenda, the Association of Coloproctology of Great Britain and Ireland (ACPGBI) sought the opinion of its members on current coloproctology training needs. The aims of this study were to canvass multidisciplinary needs and explore the perceived gaps and barriers to meeting them. METHOD: A learner-needs analysis was performed between July 2015 and October 2016. A bespoke electronic survey was sent to 1453 colorectal healthcare professionals [ACPGBI membership (1173), colorectal nurse specialists and allied health professionals (NAHPs) (261) and regional chapter-leads (19)] seeking their needs, experiences and barriers to training across the coloproctology disciplines. RESULTS: In all, 390 responses were received [26.8% overall; 180 consultants/trainees (15%); 196 NAHPs (75%); 14 (74%) chapter-leads]. Lack of funding and difficulties in obtaining study leave were the most frequently reported barriers to course and conference attendance. Transanal total mesorectal excision and laparoscopic training were the top educational needs for consultants and trainees respectively. 79% of NAHP respondents reported education gaps on a broad range of clinical and non-clinical topics. NAHPs lacked information on relevant training opportunities and 27% felt available courses were insufficient to meet their educational needs. Wide heterogeneity in ACPGBI chapter composition and activity was reported. All groups felt the ACPGBI should increase the number of courses offered with coloproctology knowledge updates commonly requested. CONCLUSION: A series of training needs across the coloproctology disciplines have been identified. These will underpin the development of the educational agenda for the ACPGBI.

Clinical outcomes of remission induction therapy for severe antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: To evaluate the reasons that complete remission is not achieved or maintained with original treatment in some patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with rituximab (RTX) or with cyclophosphamide/azathioprine (CYC/AZA). METHODS: The Rituximab in AAV trial was a randomized, double-blind, placebo-controlled trial comparing the rate of remission induction among patients treated with RTX (n = 99) and patients treated with CYC followed by AZA (n = 98). Glucocorticoids were tapered over a period of 5 months. The primary outcome measure was lack of disease activity without glucocorticoid treatment at 6 months. To determine the most important reason for failure to achieve the primary outcome, 7 hierarchical categories of reasons were defined retrospectively (uncontrolled disease, adverse event leading to therapy discontinuation, severe flare, limited flare, Birmingham Vasculitis Activity Score for Wegener's Granulomatosis >0, prednisone treatment at any dosage, and other). RESULTS: Although remission (lack of disease activity) was achieved in 170 of the 197 patients (86%) in the first 6 months, the primary outcome measure was not achieved in 42%. There were 3 deaths. Twenty-four percent of the patients failed to achieve the primary end point due to active disease: 10 (5%) experienced uncontrolled disease in the first month and 37 (19%) experienced flares after initial improvement. In the majority of such patients, treatment with blinded crossover or according to best medical judgment led to disease control. Ninety-one percent of patients who had uncontrolled disease or experienced a severe flare had proteinase 3 (PR3)-ANCA. When patients with uncontrolled disease were excluded from analysis, those who were PR3-ANCA positive were found to experience fewer flares when treated with RTX compared to CYC/AZA (8 of 59 [14%] versus 20 of 62 [32%]; P = 0.02). Neither ANCA titers nor B cell counts predicted disease flare. CONCLUSION: Current treatment regimens are largely successful in controlling AAV, but in approximately one-fourth of patients, active disease persists or recurs in the first 6 months despite treatment. PR3-ANCA positivity is a risk factor for recurrence or persistence of severe disease. ANCA titers and B cell detectability are poor predictors of both disease relapse and disease quiescence in the first 6 months.

Review: Role of early life nutrition in regulating sexual development in bulls.

The availability of high-quality semen from genetically elite bulls is essential to support continued genetic gain and the sustainability of cattle production worldwide. While reducing the age at which usable semen is available also reduces the generation interval, it is dependent on timely onset of puberty in young bulls. There is now good evidence that hastened sexual development in bulls is achieved through enhancing nutrition in early life. This review will cover the physiological and molecular-based response to prevailing diet in key organs that orchestrate the ontogeny of sexual development in the bull calf. Given the central importance of the interaction between metabolic status and neuronal function to the progression of sexual development, we will discuss how communication between metabolic organs, reproductive organs and the brain are mediated via molecular and physiological processes. The availability of high-throughput nucleic acid and protein sequencing technologies and innovative data analytics have allowed us to improve our understanding of molecular regulation of puberty and sexual development. Analysing data from a number of organs, simultaneously, allows for a better understanding of the underlying biology and biochemical interactions that are influencing sexual development. Specifically, we can determine how early life nutritional interventions augment changes in potential key molecules regulating sexual development. Ultimately, a greater understanding of the inherent regulation of postnatal sexual development in the bull calf and how strategically targeted nutritional management can advance the ontogeny of this process, will facilitate the timely availability of high-quality semen from genetically elite animals, thus supporting more economically and environmentally sustainable beef and dairy production systems.

Gene co-expression networks contributing to reproductive development in Holstein-Friesian bull calves.

Enhanced early life nutrition stimulates the functionality of the hypothalamic-pituitary-testicular (HPT) biochemical signalling axis, resulting in precocious reproductive development in bull calves. Additionally, there is evidence that peptides and hormones produced within adipose tissue depots are also central in mediating the effect of metabolic status with reproductive development. The objective of this study was to undertake gene co-expression analyses on transcriptional data of the HPT and adipose tissues derived from bull calves fed contrasting planes of nutrition up to 18 weeks of life. The relationship between networks of co-expressed genes in each tissue dataset with calf phenotypic data was also assessed using a Pearson correlation analysis. Phenotypic data were related to metabolic status (systemic concentrations of insulin, leptin, adiponectin and IGF-1) reproductive development (systemic concentrations of testosterone, FSH and LH) and markers of testicular development (seminiferous tubule diameter, seminiferous tubule lumen score, spermatogenic cells and Sertoli cells). In the hypothalamus, gene co-expression networks involved in biochemical signalling processes related to gonadotropin-releasing hormone (GnRH) secretion were positively associated (P < 0.05) with systemic concentrations of IGF-1 and insulin. Similarly, a network of gene transcripts involved in GnRH signalling in the anterior pituitary was positively associated (P < 0.05) with systemic concentrations of LH. In the testes and adipose tissues, networks of co-expressed genes implicated in cholesterol and fatty acid biosynthesis were positively associated (P < 0.05) with lumen score, Sertoli cell number, and stage of spermatogenesis. Additionally, gene co-expression networks significantly associated (P < 0.05) with both metabolic and reproductive trait data were found to be enriched (P < 0.05) for biological pathways related to energy production, cellular growth and proliferation, GnRH signalling and cholesterol biosynthesis across multiple tissues examined. Results from this study highlight networks of co-expressed genes directly associated with markers of enhanced metabolic status and subsequent earlier reproductive development. Furthermore, genes involved in biological processes mentioned above may hold potential for informing genomic selection breeding programmes for the selection of calves capable of displaying earlier reproductive development as a consequence of enhanced dietary intake.

Enhancing early life nutrition alters the hepatic transcriptome of Angus × Holstein-Friesian heifer calves.

Early life nutrition has a major influence on subsequent lifetime performance in cattle. The aim of this experiment was to investigate the effect of plane of nutrition from 3 to 21 weeks of age on the liver transcriptome. Holstein-Friesian × Angus heifer calves with a mean (±SD) age and BW of 19 (±5) days and 51.2 (±7.8) kg, respectively, were assigned to either a high-energy diet to support a mean average daily gain (ADG) of 1.2 kg/day (HI; n = 15) or a moderate diet (MOD; n = 15) to support a mean ADG of 0.5 kg/day. At 145 ±â€¯3 days of age, all calves were euthanised, liver tissue samples collected and flash-frozen in liquid nitrogen. Following RNA sequence analysis, the total number of differentially expressed genes (DEGs) (at false discovery rate (FDR) > 0.05) was 537; 308 upregulated and 229 downregulated in HI compared to MOD. The number of DEGs mapped to IPA (at FDR > 0.05) was 460; 264 upregulated and 196 downregulated. There was greater expression of genes associated with cellular development and metabolism in heifers on the HI compared to the MOD diet. The genes (fold change) of the somatotrophic axis; IGF1 (3.7), IGFALS (2.6) and GHR (1.5) were upregulated in the HI compared to MOD diet. The cytokine receptor genes, IL17RB (1.7) and IL20RA (3.3), were upregulated in the HI heifers, which were detected in a network interacting with metabolically regulated genes. The potential enhanced cell-to-cell communication evident from DEGs would increase the calves' ability to combat health challenges. The findings of this study indicate that enhancing the early life plane of nutrition in heifer calves results in the upregulation of genes that are associated with increased metabolic activity and thus metabolic capacity. Moreover, the interaction between metabolic and immune communication genes indicates that enhanced nutrition has the potential to improve the immune response in the liver which will play a central role in ensuring optimal lifetime performance.

The effect of natural and induced calving of beef heifers on stress-related gene expression and maternal health and immunity.

The peri-partum processes can exert stress on a cow on many levels. There is little evidence about acute stress around the calving event and subsequent potential effects for the cows' immunological status or subsequent reproductive health. To investigate this, 55 crossbred recipient beef heifers carrying purebred Simmental embryos were assigned to one of three groups on day 285 of gestation: (i) control (no parturition induction treatment; n = 19); (ii) induction of parturition with corticosteroid (n = 20) and (iii) induction of parturition with corticosteroid plus prostaglandin (n = 16). Interval from induction of parturition to calving and calving ease was recorded. Reproductive tract examinations were conducted on Day 21 (D21) and Day 42, and a sample was obtained for the determination of uterine cytology on D21. Blood samples were taken from the dams two weeks before parturition, one day after parturition (D1) and two weeks after parturition (D14) for gene expression and cortisol and calcium concentration determination. Calves were weighed at birth and subsequently every week until they were 10 weeks of age. A colostrum sample was taken immediately after calving and stored for subsequent Immunoglobin G (IgG) concentration analysis. Data were analysed using ANOVA with posthoc Tukey, Spearman correlation and stepwise backwards linear regression using SAS. Quantitative reverse transcription PCR was performed on the following immune genes: Interleukins IL1a and b, IL2, IL4, IL8, Tumour Necrosis Factor Alpha, Interferon-gamma, Lymphotoxin, Toll-Like Receptor, Nuclear factor of kappa light polypeptide gene enhancer in B cells 1 and 2, glucocorticoid receptor alpha, as well as the neutrophil genes that regulate inflammation: Fas, L-selectin, MMP-9 and BPI. The results show that compared with non-induced contemporaries, induction has no negative effect on dystocia or subsequent calf weight gain but can have a positive effect on colostral IgG concentration. Blood calcium concentrations on both D1 and D14 postcalving are associated with subsequent uterine health. Parturition events were reflected in temporal changes in the expression of the cytokines IFNγ, TNFα, IL1b, IL4, IL8 and Haptoglobin in the dams' blood, all of which are associated with the immune competence of the cow during this period. The conclusion is that induction of calving can have a positive effect on colostral IgG concentration. Calcium concentrations postcalving are associated with subsequent reproductive tract health. Events associated with the peri- and postpartum period are all reflected in temporal changes in immune function-related cytokines.

Genome-wide association study of economically important traits in Charolais and Limousin beef cows.

Genomic selection has proven effective for advancing genetic gain for key profit traits in dairy cattle production systems. However, its impact to-date on genetic improvement programs for beef cattle has been less effective. Despite this, the technology is thought to be particularly useful for low heritability traits such as those associated with reproductive efficiency. The objective of this study was to identify genetic variants associated with key determinants of reproductive and overall productive efficiency in beef cows. The analysis employed a large dataset derived from the national genetic evaluation program in Ireland for two of the most predominant beef breeds, viz. Charolais (n = 5 244 cows) and Limousin (n = 7 304 cows). Single nucleotide polymorphisms (SNPs) were identified as being statistically significantly associated (adj. P < 0.05) with both reproductive and productive traits for both breed types. However, there was little across breed commonality, with only two SNPs (rs110240246 and rs110344317; adj. P < 0.05) located within the genomic regions of the LCORL and MSTN genes respectively, identified in both Charolais and Limousin populations, associated with traits including carcass weight, cull-cow weight and live-weight. Significant SNPs within the MSTN gene were also associated with both reproduction and production related traits within each breed. Finally, traits including calving difficulty, calf mortality and calving interval were associated with SNPs within genomic regions comprising genes involved in cellular growth and lipid metabolism. Genetic variants identified as associated with both important reproductive efficiency and production related traits from this study warrant further analyses for their potential incorporation into breeding programmes to support the sustainability of beef cattle production.

Effect of dietary restriction and subsequent realimentation on hepatic oxidative phosphorylation in cattle.

Compensatory growth (CG) is a naturally accelerated growth which occurs upon realimentation, following a prior period of dietary restriction. The process is harnessed worldwide as a management practice to reduce feed costs in beef cattle production. The objective of this study was to assess the potential contribution of hepatic cellular mitochondrial capacity to CG through global hepatic oxidative phosphorylation gene expression analyses as well as functional mitochondrial enzyme activity assays. Holstein-Friesian bulls were separated into two groups: (i) restricted feed allowance for 125 days (Period 1) (RES; n = 30) followed by ad-libitum feeding for 55 days (Period 2) or (ii) ad-libitum access to feed throughout (Periods 1 and 2) (ADLIB; n = 30). At the end of each period, 15 animals from each treatment group were slaughtered and hepatic tissue was collected. Tissue samples were subjected to RNAseq and spectrophotometric analysis for the functional assessment of mitochondria. RES and ADLIB groups grew at 0.6 kg/day and 1.9 kg/day, respectively, during Period 1. During Period 2, the RES group underwent CG growing at 2.5 kg/day, with ADLIB animals gaining 1.4 kg/day. Oxidative phosphorylation genes were differentially expressed in response to both dietary restriction and CG. Spectrophotometric assays indicated that mitochondrial abundance was greater in animals undergoing dietary restriction at the end of Period 1 and subsequently reduced during realimentation (P < 0.02). Results indicate that mitochondrial capacity may be enhanced during dietary restriction to more effectively utilize diet-derived nutrients. However, enhanced mitochondrial capacity does not appear to be directly contributing to CG in cattle.

Effect of dietary restriction and compensatory growth on performance, carcass characteristics, and metabolic hormone concentrations in Angus and Belgian Blue steers.

Compensatory growth (CG) is the ability of an animal to undergo accelerated growth after a period of restricted feeding. However, there is a dearth of information in relation to the effect of genotype on CG response, thus the objective of this study was to evaluate CG response in two contrasting breed types, namely Aberdeen Angus (AN) and Belgian Blue (BB). Crossbred AN × Holstein-Friesian or BB × Holstein-Friesian steers were assigned to one of two treatment groups in a two (genotypes) × two (diets) factorial design. For 99 days, one group (11 AN and 12 BB) was offered a high energy control diet (H-H) whereas the second group (11 AN and 12 BB) was offered an energy restricted diet (L-H). At the end of the differential feeding period (99 days), both groups of animals were then offered a high energy control diet for a further 200 days. All animals were then slaughtered on day-299 of the study. During feed restriction, L-H had lower DM intake (DMI), had greater feed conversion ratio (FCR) and lower plasma concentrations of insulin, IGF-1, leptin, glucose, urea, betahydroxybutyrate and smaller M. longissimus thoracis or lumborum muscle and fat depths compared to H-H steers. During realimentation, there was no difference in DMI between diets; however, L-H had greater live weight gain compared to H-H steers. Overall, H-H consumed greater quantities on a DM basis, however, had a higher FCR compared to L-H steers. By the end of the realimentation period, there was no difference in plasma metabolite or hormone concentrations, linear body measurements, ultrasonically scanned fat depths, carcass conformation, dressing percentage or fat class between H-H and L-H steers. At slaughter, carcass weights were affected by diet with greater values for H-H compared to L-H steers. Genotype affected measures associated with body composition including pelvic width and both muscle and fat depths (P < 0.05). Overall, L-H had a CG (or recovery) index of 0.52 and did not make up for the loss of gains during the differential feeding period; however, M. longissimus thoracis et lumborum, a tissue of high economic value, recovered completely making it a target of interest for further investigation.

Blood immune transcriptome analysis of artificially fed dairy calves and naturally suckled beef calves from birth to 7 days of age.

Neonatal calves possess a very immature and naïve immune system and are reliant on the intake of maternal colostrum for passive transfer of immunoglobulins. Variation in colostrum management of beef and dairy calves is thought to affect early immune development. Therefore, the objective of this study was to examine changes in gene expression and investigate molecular pathways involved in the immune-competence development of neonatal Holstein dairy calves and naturally suckled beef calves using next generation RNA-sequencing during the first week of life. Jugular whole blood samples were collected from Holstein (H) dairy calves (n = 8) artificially fed 5% B.W. colostrum, and from beef calves which were the progenies of Charolais-Limousin (CL; n = 7) and Limousin-Friesian beef suckler cows (LF; n = 7), for subsequent RNA isolation. In dairy calves, there was a surge in pro-inflammatory cytokine gene expression possibly due to the stress of separation from the dam. LF calves exhibited early signs of humoral immune development with observed increases in the expression genes coding for Ig receptors, which was not evident in the other breeds by 7 days of age. Immune and health related DEGs identified as upregulated in beef calves are prospective contender genes for the classification of biomarkers for immune-competence development, and will contribute towards a greater understanding of the development of an immune response in neonatal calves.

Feed restriction and subsequent realimentation in Holstein Friesian bulls: I. Effect on animal performance; muscle, fat, and linear body measurements; and slaughter characteristics.

Holstein Friesian bulls (n = 75) were used to evaluate the effect of restricted and subsequent compensatory growth on muscular and skeletal growth as well as the recovery of carcass and noncarcass components. Fifteen bulls were slaughtered on Day 0 to provide baseline parameters for carcass and noncarcass measurements. Of the remaining 60 bulls, 30 were fed ad libitum (ADLIB) and 30 were fed a restricted (RES) diet to grow at 0.6 kg/d for 125 d, denoted as Period 1. After 125 d of differential feeding, 15 bulls from each group were slaughtered. The remaining bulls in both treatment groups were then offered ad libitum access to feed for a further 55 d (realimentation), denoted as Period 2, after which they were also slaughtered. All animals received the same diet composed of 70% concentrate and 30% grass silage throughout the experimental trial. As planned, feed intake was greater for ADLIB bulls in Period 1 (P < 0.001); however, there was no difference in feed intake during realimentation (P > 0.05). During Period 1, RES bulls gained 0.6 kg/d whereas ADLIB bulls grew at 1.9 kg/d. During realimentation in Period 2, RES bulls displayed accelerated growth, gaining 2.5 kg/d compared with 1.4 kg/d for ADLIB bulls (P < 0.001). This amounted to a live weight difference between treatment groups of 161 kg at the end of Period 1 after restricted feeding, which was then reduced to 84 kg at the end of Period 2 (P < 0.001). Restricted animals achieved a compensatory growth (or recovery) index of 48% within 55 d of realimentation. During Period 2, RES bulls displayed a better feed conversion ratio (P < 0.001) than ADLIB bulls, indicating better feed efficiency. Ultrasonically measured longissmus dorsi growth was greater for ADLIB bulls compared with RES bulls during Period 1; however, this was reversed during Period 2 (P < 0.001). Metabolically active organs such as the liver and components of the gastrointestinal tract were lighter in RES bulls at the end of Period 1, with no difference in the weights of these components after realimentation (P < 0.01). The improved feed efficiency and muscle growth observed during feed restriction induced compensatory growth may be as a consequence of latent effects of reduced requirements of energetically demanding tissues into realimentation.

Feed restriction and realimentation in Holstein-Friesian bulls: II. Effect on blood pressure and systemic concentrations of metabolites and metabolic hormones.

The objective of this study was to evaluate the endocrine response and metabolic rate in Holstein­Friesian bulls during restricted feeding and realimentation. Sixty bulls were allocated to 1 of 2 feeding regimes: 1) restricted feed allowance (RES; n = 30) or 2) ad libitum feeding (ADLIB; n = 30) for 125 d (Period 1). The bulls in both treatment groups were then offered ad libitum access to feed for a further 55 d (Period 2). Five and 4 blood samples were collected during periods 1 (n = 60) and 2 (n = 30), respectively. Plasma samples were assayed for hormones and metabolites including insulin, IGF-1, leptin, thyroid hormones, albumin, ß-hydroxy butyrate (BHB), creatinine, glucose, NEFA, total protein, triglycerides, and urea. Blood pressure measurements were determined on all animals at the beginning and end of each period as an indicator of metabolic rate. During Period 1, RES bulls gained 0.6 kg/d whereas ADLIB bulls grew at 1.9 kg/d. Following realimentation in Period 2, RES bulls displayed accelerated growth, gaining 2.5 kg/d compared with 1.4 kg/d for ADLIB bulls (P < 0.001). Treatment × period interactions (P < 0.05) were evident for all plasma analytes assayed. During Period 1, RES bulls had lower concentrations of glucose and insulin, reflecting their lower feed intake. Adipose and protein tissue mobilization was evident through greater concentrations of triglycerides, NEFA, BHB, creatinine, albumin, and total protein in RES animals in Period 1. Additionally, the effect of restricted feeding on growth was apparent through lower concentrations of IGF-1. A lower metabolic rate was also apparent through lower concentrations of thyroid hormones and fewer beats per minute in RES bulls during Period 1. During the initial stage of realimentation in Period 2, IGF-1, insulin, thyroid hormones, creatinine, glucose, total protein, and triglycerides followed the same pattern as per Period 1 with divergence maintained between RES and ADLIB bulls (P < 0.05), whereas concentrations of all of these hormones and metabolites had converged between the treatment groups by the end of Period 2. During realimentation, the number of heart beats per minute was greater in RES bulls, indicating greater metabolic rate in these animals (P < 0.001). Results from the current study clearly show that feed restriction followed by realimentation affects key indices of metabolic status as well as tissue catabolism and provides an insight into the metabolic control of compensatory growth in cattle.

Rituximab for the treatment of relapses in antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: Disease relapses are frequent in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). This study was undertaken to evaluate outcomes in patients with AAV who are re-treated with rituximab (RTX) and prednisone for severe disease relapses. METHODS: The Rituximab in AAV trial was a randomized, double-blind, placebo-controlled trial comparing the rates of remission induction among patients treated with RTX (n = 99) and patients treated with cyclophosphamide (CYC) followed by azathioprine (AZA) (n = 98). Prednisone was tapered to discontinuation after 5.5 months. After remission was achieved, patients who experienced a severe disease relapse between months 6 and 18 were eligible to receive RTX and prednisone on an open-label basis according to a prespecified protocol. Investigators remained blinded with regard to the original treatment assignment. RESULTS: Twenty-six patients received RTX for disease relapse after remission had initially been achieved with their originally assigned treatment. Fifteen of these patients were initially randomized to receive RTX and 11 to receive CYC/AZA. Thirteen (87%) of the patients originally assigned to receive RTX and 10 (91%) originally assigned to receive CYC/AZA achieved remission again with open-label RTX (an overall percentage of 88%). In half of the patients treated with open-label RTX, prednisone could be discontinued entirely. Patients in this cohort experienced fewer adverse events compared to the overall study population (4.7 adverse events per patient-year versus 11.8 adverse events per patient-year). CONCLUSION: Re-treatment of AAV relapses with RTX and glucocorticoids appears to be a safe and effective strategy, regardless of previous treatment.

Angiotensin II antagonism fails to ameliorate bleomycin-induced pulmonary fibrosis in mice.

Based on current evidence, transforming growth factor (TGF)-beta plays a central pathogenic role in the development of pulmonary fibrosis. There is growing evidence that angiotensin II can serve as a stimulus for TGF-beta-mediated lung fibrosis. However, the role of angiotensin II in the pathobiology of pulmonary fibrosis in vivo remains unclear and the therapeutic potential for targeting angiotensin II in a bleomycin-induced pulmonary fibrosis model is not well known. Therefore, the aim of this study was to test whether the angiotensin II antagonist, losartan, attenuated the development of bleomycin-induced pulmonary fibrosis in two distinct murine strains, C57/BL6 and Sv129. This was determined by histopathology and quantification of collagen content by hydroxyproline assay. Despite demonstrable angiotensin II antagonism in vivo and a reduction in measures of acute lung injury, losartan therapy, at a dose shown to reduce renal and cardiac fibrosis in mice, failed to significantly ameliorate bleomycin-induced pulmonary fibrosis. In conclusion, these data suggest that the pulmonary fibrotic disease process in vivo is not solely dependent on angiotensin II activity and the potential for angiotensin II receptor blockers as a therapeutic strategy in patients with pulmonary fibrosis may be limited.

Structural similarities between myelin and hydrophobic surfactant associated proteins: protein motifs for interacting with bilayers.

A group of predicted structural similarities exist between the hydrophobic pulmonary surfactant protein SP-B and SP-C and the hydrophobic proteins of myelin, either the myelin basic protein and the proteolipid protein of central nervous system myelin, or the P0 protein of peripheral myelin. These similarities include, among other factors, the charge density, post-translational modification by fatty acids, some potential periodicity in primary structure and an overall hydrophobicity. The similarities suggest that these proteins might have similar means of interacting with each other and with lipid bilayers in their respective biological systems.

The Palliative Care Education Group for Gloucestershire (PEGG): an integrated model of multidisciplinary education in palliative care.

Multidisciplinary teamwork is an essential part of palliative care. Traditionally, in the UK, education of health care professionals has been carried out within single professional disciplines. The Palliative Care Education Group (PEGG) for Gloucestershire, a county in the south-west region of England, UK, is a multidisciplinary group, which promotes and integrates palliative care education across the county. This report describes the evolution of the group, its aims and objectives and the methods used to evaluate its impact on clinical practice. PEGG is a practical model of multidisciplinary education, which could be adopted in other areas.

Biallelic expression of the IGF2 gene in human breast disease.

We examined the imprinting status of the insulin-like growth factor II gene (IGF2) in a series of 20 human breast disease samples to determine if disrupted imprinting (as evidenced by biallelic expression), was a demonstrable mechanism of altered gene expression. These samples included benign (n = 7) and malignant breast lesions (n = 13). Biallelic expression of IGF2 was detectable in 67% of benign and 60% of malignant informative breast lesions. Three informative reduction mastectomies displayed normal IGF2 imprinting. The presence of this alteration in human breast tissue is a novel finding, and may contribute to tumorigenesis, possibly by favouring an enhanced proliferative milieu, during which additional mutations could occur.

Predictors of hospitalization in children with acute asthma.

OBJECTIVE: To identify predictors of long duration of bronchodilator therapy in children with acute asthma. STUDY DESIGN: An emergency department prospective cohort study of 278 children > or =12 months of age, with clinical and socioeconomic parameters collected at baseline and 4 hours after administration of corticosteroids. Patients were classified into short and long therapy groups, with interval from first albuterol dose to initiation of administration every 4 hours < or =12 or >12 hours, respectively. Predictors significant by univariate analysis were examined by multiple logistic regression. RESULTS: Five variables were associated with long therapy (n = 85) versus short therapy (n = 193): previous intensive care unit admission (odds ratio [OR] 7.2, 95% CI = 1.85, 27.7); baseline oxygen saturation < or =92% (OR 2.6, 95% CI = 0.89, 7.4), asthma score > or =6/9 (OR 2.9, 95% CI = 1.9, 4.37), oxygen saturation < or =92% (OR 6.6, 95% CI = 1.34, 32.0), and hourly albuterol dosing interval (OR 4.3, 95% CI = 0.82, 22.12) 4 hours after administration of corticosteroids. Probability of long therapy was 91.8% to 99% for > or =3 predictors, but only 40.6% to 61.8% for individual factors. CONCLUSION: A combination of 3 or more factors predicts long bronchodilator therapy and signals the need for hospitalization. Children with only one predictor can be safely treated in the emergency department or observation unit and reevaluated.