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.

Compensatory growth in crossbred Aberdeen Angus and Belgian Blue steers: Effects on the colour, shear force and sensory characteristics of longissimus muscle.

The effect of feed restriction (99days) followed by compensatory growth during a 200day re-alimentation period on the colour and sensory characteristics of meat from Aberdeen Angus×Holstein-Friesian (AN) and Belgian Blue×Holstein-Friesian (BB) steers was examined. Compensatory growth had no effect on muscle pH and temperature decline, chemical composition, drip loss, fat colour, or juiciness, but increased (P=0.009) Warner-Bratzler shear force and decreased tenderness (P=0.08) and overall liking (P=0.09). Compared to meat from BB steers, meat from AN steers had a higher intramuscular fat concentration and was rated similarly for tenderness, but higher for many of the flavour characteristics examined. While adjustment for intramuscular fat concentration removed some of these differences, genotype-specific flavour differences remained. It is concluded that genotype had greater effects on meat quality than the compensatory growth feeding regime imposed in this study.

Fertility and genomics: comparison of gene expression in contrasting reproductive tissues of female cattle.

To compare gene expression among bovine tissues, large bovine RNA-seq datasets were used, comprising 280 samples from 10 different bovine tissues (uterine endometrium, granulosa cells, theca cells, cervix, embryos, leucocytes, liver, hypothalamus, pituitary, muscle) and generating 260 Gbases of data. Twin approaches were used: an information-theoretic analysis of the existing annotated transcriptome to identify the most tissue-specific genes and a de-novo transcriptome annotation to evaluate general features of the transcription landscape. Expression was detected for 97% of the Ensembl transcriptome with at least one read in one sample and between 28% and 66% at a level of 10 tags per million (TPM) or greater in individual tissues. Over 95% of genes exhibited some level of tissue-specific gene expression. This was mostly due to different levels of expression in different tissues rather than exclusive expression in a single tissue. Less than 1% of annotated genes exhibited a highly restricted tissue-specific expression profile and approximately 2% exhibited classic housekeeping profiles. In conclusion, it is the combined effects of the variable expression of large numbers of genes (73%-93% of the genome) and the specific expression of a small number of genes (<1% of the transcriptome) that contribute to determining the outcome of the function of individual tissues.

Effect of sire breed and genetic merit for carcass weight on the transcriptional regulation of the somatotropic axis in longissimus dorsi of crossbred steers.

The somatotropic axis plays an important role in postnatal growth, development, and differentiation of skeletal muscle. The aim of this study was to examine the effect of sire breed and sire EPD for carcass weight (EPD(cwt)) on the expression of components of the somatotropic axis in LM of beef cattle at slaughter. Crossbred Aberdeen Angus (AA; n = 17) and Belgian Blue (BB; n = 16) steers born to Holstein-Friesian dams and sired by bulls with either high (H) or low (L) EPD(cwt) were used in the study. Thus, there were 4 genetic groups [i.e., BBH (n = 8), BBL (n = 8), AAH (n = 8), and AAL (n = 9)]. Blood samples were collected via jugular venipuncture at regular intervals for analysis of plasma concentrations of IGF-1 and insulin. Total RNA was isolated from LM collected at slaughter, and the mRNA expression of IGF-1, IGF-2, their receptors (IGF-1R; IGF-2R), 6 IGFBP, acid labile subunit (ALS), and GH receptor (GHR) was measured by real-time reverse-transcription quantitative PCR. There was no effect of either sire breed or EPD(cwt) on concentrations of circulating IGF or insulin (P > 0.05). Gene expression of IGF-1R and IGFBP3 was upregulated in AA (P < 0.001) compared with BB, whereas IGF-1 was upregulated in H compared with L animals (P < 0.01). Correlation analysis indicated moderate positive associations between gene expression of IGFBP3 and IGF-1 (r = 0.54; P < 0.001) and IGF-1R (r = 0.48; P < 0.01). In addition, correlation analysis revealed that mRNA expression of IGFBP3 was moderately negatively associated with LM area per kilogram of carcass weight (r = -0.40; P < 0.05). Greater gene expression of IGF-1 and reduced transcript abundance of IGFBP3 in muscle may have a role in increased muscle growth potential in steers during the finishing period. These data will contribute to a better understanding of the molecular control of muscle growth at a tissue level in cattle.

Insulin pumps: from inception to the present and toward the future.

As an alternative to the usual insulin injections, insulin pumps have been introduced as an advanced method of insulin delivery for managing type 1 diabetes mellitus patients. This review documents the history of insulin pump development and the production of 'smart pumps' that offer patients greater dosing accuracy, flexibility, and ease of use. This has resulted in an increase in the number of insulin pump users around the world. This paper also provides a comprehensive survey of the pumps currently available on the market and their specifications. Unique features of each product and the drawbacks are addressed in the review. The future direction of insulin pump development is targeted toward closing the loop, to allow feedback control between an insulin pump and a glucose sensor, and hence finer adjustment of insulin delivery rates as required.

Medicines for chronic illness at school: experiences and concerns of young people and their parents.

BACKGROUND AND OBJECTIVE: Access to medicines by young people with chronic conditions during the school day and suitable environments and support in the administration of a range of dosage forms may be required for optimal clinical management. Whilst Government policy emphasizes that children and young people with chronic illness should be able to lead as normal lives as possible, there is only limited evidence on the experiences and concerns of young people and their parents regarding the use of medicines at school and the impact on school life. The objective of this study was to examine the experiences and concerns of young people with chronic conditions, and their parents/carers, in managing medication at school. METHODS: Data were gathered in audio-recorded face-to-face semi-structured interviews with 27 young people (5-18 years) and their parents attending out-patient clinics at a major London teaching hospital. Open-ended questions provided an opportunity for participants to describe experiences and views in the context of their activities, priorities and concerns and enabled a qualitative analysis. RESULTS AND DISCUSSION: The findings indicated that storage and access of medicines did not present major problems for young people receiving regular medication. However, those receiving medication on a 'when required' basis reported barriers to access. The most common concern regarding taking medication was lack of privacy, which sometimes led to non-adherence. Adverse effects of medication were highlighted as a cause of both non-adherence and poorer school performance. Extracurricular activities such as school trips were not viewed as presenting a problem by those who were interviewed. However, this was often because young people and their families devised their own strategies regarding the use of medicines that did not depend on the input of staff. There was wide variation in responses about the support young people received from school staff, with evidence of helpful and unhelpful practice. The potential benefits of liaison between schools and health professionals to assist schools in their support of students with their medicines were highlighted. CONCLUSION: This study has identified medication-related issues from the perspective of young people and their parents, indicating ways in which their needs might be served more sensitively and effectively.

Infliximab delays but does not avoid the need for surgery in treatment-resistant pediatric Crohn' disease.

The aim of this study was to review the impact of infliximab therapy on children with treatment-resistant Crohn's disease. Treatment resistance was defined as clinically active disease despite >4 months of immunosuppressive therapy. The outcome variables were time to first remission, duration of remission and the need for surgery. 24 children received 90 infusions of infliximab (16 boys; median 10.3y, range 1.0-14.4y); all had three infusions as an induction course. 17 (70.8%) achieved clinical remission, with 14/17 (82.3%) relapsing within 4 months of the third infusion. 6/7 in the non-responding group and 8/17 of the responders required surgery with an insignificant difference in the median time to surgery (p=0.49). Four remain dependent on regular infliximab. Infliximab is well-tolerated and highly effective in achieving clinical remission in children with refractory Crohn's disease but may only delay and not avoid the need for surgery. Failure to achieve clinical remission by the 3rd infusion significantly increases the risk of surgery.

Effect of Gaviscon Infant on gastro-oesophageal reflux in infants assessed by combined intraluminal impedance/pH.

BACKGROUND: Gaviscon Infant (GI) has been recommended for gastro-oesophageal reflux (GOR) in infants. Its efficacy has not been examined with a physiologically appropriate denominator to define the degree of GOR. AIM: To investigate the influence of Gaviscon Infant on GOR in infants using combined pH and intraluminal impedance measurement. METHODS: Twenty infants (mean age 163.5 days, range 34-319 days) exclusively bottle fed, with symptoms clinically suggestive of GOR, underwent 24 hour studies of intra-oesophageal 6 channel impedance and dual channel pH monitoring, during which six random administrations (3+3) of Gaviscon Infant (625 mg in 225 ml milk) or placebo (mannitol and Solvito N, 625 mg in 225 ml milk) were given in a double blind fashion. Impedance/pH reflux data were recorded and analysed blind by one observer. RESULTS: The median number of reflux events/hour (1.58 v 1.68), acid reflux events/hour (0.26 v 0.43), minimum distal or proximal pH, total acid clearance time per hour (time with pH below pH 4), and total reflux duration per hour were not significantly different after GI than after placebo. Reflux height was marginally lower after GI (median 66.6% v 77.3% oesophageal length) compared with placebo. CONCLUSIONS: Results showed a marginal but significant difference between Gaviscon Infant and placebo in average reflux height, and raises questions regarding any perceived clinical benefit of its use.

Adverse psychological effects of corticosteroids in children and adolescents.

Children and adolescents treated with oral, inhaled, and intravenous corticosteroids (CS) may experience adverse psychological side effects (APSE), including psychotic symptoms. These can occur at any point during treatment, including withdrawal. In this paper the literature on these effects in children and adults is reviewed. From the evidence available, it is not possible to give reliable estimates for incidence or prevalence of APSE, nor clear risk factors. Some evidence is reported to suggest that oral dexamethasone treatment may carry a higher risk of APSE than other CS, but this requires further investigation. There is evidence from the adult literature that higher CS doses increase the risk of APSE. However, the dose response effect is not straightforward or predictable for individuals or groups. This is likely to be a reflection of the complex effects of CS on the central nervous system and the probable interplay between individual susceptibility, disease factors, and external environmental stressors in the emergence of APSE. More research is required to further our understanding of the adverse effects of these clinically valuable agents.

High-dose azathioprine in children with inflammatory bowel disease.

BACKGROUND: Azathioprine is widely used as maintenance therapy in children with moderate to severe inflammatory bowel disease (IBD). There is no data on safety at higher doses and its impact on growth and surgical morbidity in children. METHODS: This retrospective cohort study included all children treated with azathioprine and diagnosed with IBD between 1996-2001. Outcome measures included indications for azathioprine use, adverse-effects and reasons for treatment discontinuation. Height and weight at diagnosis, treatment onset and current follow-up was recorded, and Z scores for height standardised for time. RESULTS: 107 children received azathioprine at 3 mg/kg. 61% had Crohn's disease and 83% started azathioprine within 2 years of diagnosis. Only 2/107 children had to stop azathioprine because of persistent adverse effects and 16/107 required surgery. There was a trend toward better growth in a group of children with Crohn's disease following treatment with high dose azathioprine therapy (P = 0.08). CONCLUSIONS: Azathioprine is a safe and well-tolerated maintenance therapy at 3 mg/kg for children with IBD. The prevalence of surgery and growth failure in a cohort of children with moderate to severe IBD appears less than previously reported. In children with Crohn's disease, growth velocity may be maximised by an emphasis on nutritional therapy and the use of high dose azathioprine.

Use of unlicensed and off-label medications in paediatric gastroenterology with a review of the commonly used formularies in the UK.

BACKGROUND: Use of unlicensed and off-label medications is common in hospital based paediatric practice. Whilst inpatient prescription can be closely monitored within the hospital setting, it is subspecialties like paediatric gastroenterology, caring for chronically ill children on an outpatient basis that require administration of regular medications in the community. Local practitioners rely on available paediatric formularies or information provided by the tertiary unit for monitoring and dispensing further prescriptions. AIM: To assess the proportion of unlicensed and off-label medications prescribed in a paediatric gastroenterology unit to children discharged to the community and assess adequacy of information about these medications in commonly used British formularies. METHODS: All prescriptions prescribed over a six-month period (Jan-Jul 2002) either in the paediatric gastroenterology outpatient department or for children discharged home after an inpatient stay, were retrieved from the pharmacy database. The main outcome measures were to assess the proportion of medications prescribed for unlicensed or off-label use. RESULTS: 308 patients received 777 prescriptions of which 384 (49%) were for unlicensed or off-label use. Of these 291 (76%) were off-label; 208 in relation to indication and 83 to child's age. 93 of the prescribed medications were unlicensed; 37 were due to manipulation of formulation. Of the commonly used formularies in the UK, only 'Medication for Children(R)' contained dosage information on more than half (9/13) of the most often prescribed off-label/unlicensed medications in paediatric gastroenterology. CONCLUSIONS: Use of unlicensed and off-label medications remains a problem in paediatric practice. Until licensing laws change and more drugs are licensed in children, paediatric gastroenterologists remain responsible for provision of information to families, local practitioners, nurses and pharmacists. Of the commonly used formularies, 'Medicines for Children' is the most detailed and comprehensive, and should be available to all general practitioners and pharmacists in the UK. Clear communication between specialist units and local practitioners is imperative to ensure safe and effective prescribing to children.