18†Engaging with young people to improve research, services and workforce development: eye-YPAG and 'visually' workshops.

Involving children and young people (CYP) in service and research design improves quality and accessibility. Running events in schools to invite CYP to volunteer and explore careers in the NHS may contribute to uptake of training posts and developing the NHS workforce.Here we evaluate two activities with CYP, our Young Person's Advisory Group for research (eye-YPAG) and our workshop for secondary schools, 'visually'.We evaluated eye-YPAG in focus groups and online surveys with group members, parents/carers, researchers, facilitators and funders. We conducted thematic analysis and descriptive statistics. To evaluate 'visually', we monitored the numbers of workshops and young people applying for volunteering roles. We asked those who started working with us about their experience.eye-YPAG members valued social and creative aspects as well as learning about research and developing skills and confidence. Researchers reported that CYP gave novel suggestions, modifying research plans, and that their different perspective was helpful in making research more relevant for children and families.Over 6 months, we held 15 'visually' workshops in secondary schools. Ninety students applied for volunteering roles, and 20 have completed the Human Resources onboarding process. Young volunteers report that this work has increased their confidence and that they have gained insights into how a hospital works. One is considering training to become an orthoptist.Both eye-YPAG and 'visually' are available to all eye researchers and units in the UK and can facilitate outreach activities.

Revised QUICKI provides a strong surrogate estimate of insulin sensitivity when compared with the minimal model.

OBJECTIVE: To compare insulin sensitivity (Si) from a frequently sampled intravenous glucose tolerance test (FSIGT) and subsequent minimal model analyses with surrogate measures of insulin sensitivity and resistance and to compare features of the metabolic syndrome between Caucasians and Indian Asians living in the UK. SUBJECTS: In all, 27 healthy male volunteers (14 UK Caucasians and 13 UK Indian Asians), with a mean age of 51.2+/-1.5 y, BMI of 25.8+/-0.6 kg/m(2) and Si of 2.85+/-0.37. MEASUREMENTS: Si was determined from an FSIGT with subsequent minimal model analysis. The concentrations of insulin, glucose and nonesterified fatty acids (NEFA) were analysed in fasting plasma and used to calculate surrogate measure of insulin sensitivity (quantitative insulin sensitivity check index (QUICKI), revised QUICKI) and resistance (homeostasis for insulin resistance (HOMA IR), fasting insulin resistance index (FIRI), Bennetts index, fasting insulin, insulin-to-glucose ratio). Plasma concentrations of triacylglycerol (TAG), total cholesterol, high density cholesterol, (HDL-C) and low density cholesterol, (LDL-C) were also measured in the fasted state. Anthropometric measurements were conducted to determine body-fat distribution. RESULTS: Correlation analysis identified the strongest relationship between Si and the revised QUICKI (r=0.67; P=0.000). Significant associations were also observed between Si and QUICKI (r=0.51; P=0.007), HOMA IR (r=-0.50; P=0.009), FIRI and fasting insulin. The Indian Asian group had lower HDL-C (P=0.001), a higher waist-hip ratio (P=0.01) and were significantly less insulin sensitive (Si) than the Caucasian group (P=0.02). CONCLUSION: The revised QUICKI demonstrated a statistically strong relationship with the minimal model. However, it was unable to differentiate between insulin-sensitive and -resistant groups in this study. Future larger studies in population groups with varying degrees of insulin sensitivity are recommended to investigate the general applicability of the revised QUICKI surrogate technique.

Lack of association between central adiposity and lipaemia in UK Sikh men.

OBJECTIVE: To determine whether the positive statistical associations between measures of total and regional adiposity and measures of glucose, insulin and triacylglycerol (TAG) metabolism reported in Caucasian men, are also observed in UK Sikhs. DESIGN: A matched cross-sectional study in which each volunteer provided a blood sample after a 12-h overnight fast and had anthropometric measurements taken. SUBJECTS: A total of 55 healthy Caucasian and 55 healthy UK Sikh men were recruited. The Caucasian and Sikh men were matched for age (48.7+/-10.9 and 48.3+/-10.0 y, respectively) and body mass index (BMI) (26.1+/-2.8 and 26.3+/-3.2 kg/m(2), respectively). MEASUREMENTS: Anthropometric measurements were performed to assess total and regional fat depots. The concentrations of plasma total cholesterol, high-density cholesterol (HDL-C), low-density cholesterol (LDL-C) and small dense LDL (LDL3), TAG, glucose, fasting insulin (ins) and nonesterified fatty acids (NEFA) were analysed in fasted plasma. Surrogate measures of insulin resistance (HOMA-IR) and insulin sensitivity (RQUICKI) were calculated from insulin and glucose (HOMA-IR) and insulin, glucose and NEFA (RQUICKI) measurements. RESULTS: The Sikh men had significantly higher body fat, with the sum of the four skinfold measurements (Ssk) (P=0.0001) and subscapular skinfold value (P=0.009) higher compared with the Caucasian men. The Sikh volunteers also had characteristics of the metabolic syndrome: lower HDL-C (P=0.07), higher TAG (P=0.004), higher % LDL3 (P=0.0001) and insulin resistance (P=0.05). Both ethnic groups demonstrated positive correlations between insulin and waist circumference (Caucasian: r=0.661, P=0.0001; Sikh: r=0.477, P=0.0001). The Caucasian men also demonstrated significant positive correlations between central adiposity (r=0.275, P=0.04), other measures of adiposity (BMI and suprailiac skinfold) and plasma TAG, whereas the Sikh men showed no correlation for central adiposity (r=0.019, ns) and TAG with a trend to a negative relationship between other measures (Ssk and suprailiac) which reached near significance for subscapular skinfold and TAG (r=-0.246, P=0.007). The expected positive association between insulin and TAG was observed in the Caucasian men (r=0.318, P=0.04) but not in the Sikh men (r=0.011, ns). CONCLUSIONS: In the Caucasian men, the expected positive association between plasma TAG and centralized body fat was observed. However, a lack of association between centralized, or any other measure of adiposity, and plasma TAG was observed in the matched Sikh men, although both ethnic groups showed the positive association between centralized body fat and insulin resistance, which was less strong for Sikhs. These findings in the Sikh men were not consistent with the hypothesis that there is a clear causal relationship between body fat and its distribution, insulin resistance, and lipid abnormalities associated with the metabolic syndrome, in this ethnic group.

Comparison of dietary fat and fatty acid intake estimated by the duplicate diet collection technique and estimated dietary records.

INTRODUCTION: A high saturated fatty acid intake is a well recognized risk factor for coronary heart disease development. More recently a high intake of n-6 polyunsaturated fatty acids (PUFA) in combination with a low intake of the long chain n-3 PUFA, eicosapentaenoic acid and docosahexaenoic acid has also been implicated as an important risk factor. AIM: To compare total dietary fat and fatty acid intake measured by chemical analysis of duplicate diets with nutritional database analysis of estimated dietary records, collected over the same 3-day study period. METHODS: Total fat was analysed using soxhlet extraction and subsequently the individual fatty acid content of the diet was determined by gas chromatography. Estimated dietary records were analysed using a nutrient database which was supplemented with a selection of dishes commonly consumed by study participants. RESULTS: Bland & Altman statistical analysis demonstrated a lack of agreement between the two dietary assessment techniques for determining dietary fat and fatty acid intake. CONCLUSION: The lack of agreement observed between dietary evaluation techniques may be attributed to inadequacies in either or both assessment techniques. This study highlights the difficulties that may be encountered when attempting to accurately evaluate dietary fat intake among the population.

Comparison of children's dietary intake patterns with US dietary guidelines.

Monitoring dietary intake patterns among children is important in order to explore and prevent the onset of adult health problems. The aim of the present study was to compare children's dietary intakes with national recommendations and to determine whether sex or ethnic differences were evident. This was done using a methodology that allows assessment of intake from the major components of the Food Guide Pyramid developed by the United States Department of Agriculture (USDA: US Department of Agriculture and US Department of Health and Human Services (1992)). The sample studied included 110 African-American and Caucasian males and females (mean age 9.9 years, BMI 20.1 kg/m2) from Birmingham, AL, USA, who were participating in a study investigating the development of obesity. Dietary data were based on three 24 h recalls and food group intake was determined using the USDA Pyramid Servicing Database. The results indicated that a high percentage of subjects failed to meet the recommended number of servings from each of the food groups. For example, only 5 % and 9 % met fruit and dietary group recommendations respectively. Consumption of foods from the Pyramid 'tip' (including discretionary fat and added sugar) contributed almost 50 % of the diet. African-Americans were more likely to meet requirements for the meat group, with a higher proportion of Caucasians meeting dietary recommendations. Males were more likely to meet the vegetable group guidelines although females consumed more energy per day from discretionary fat. In conclusion, these results suggest that implementation of nutrition education programmes may be important for promoting healthy nutrition among American children.

Primary living-donor liver transplantation at the University of Chicago: technical aspects of the first 104 recipients.

OBJECTIVE: To evaluate the impact of technical modifications on living-donor liver transplants in children since their introduction in 1989. SUMMARY BACKGROUND DATA: Although more than 4,000 liver transplants are performed every year in the United States, only approximately 500 are performed in children. Living-donor liver transplantation has helped to alleviate the organ shortage for small children in need of liver transplantation. Few centers have amassed a sufficient number of cases to evaluate the impact of the different techniques used in pediatric living-donor liver transplantation. METHODS: From 1989 through 1997, 104 primary living-donor liver transplants were performed at the University of Chicago. Three phases of the living-donor liver transplant program can be defined based on the techniques of vascular reconstruction: phase 1, November 1989 to November 1994 (n = 78); phase 2, November 1994 to January 1996 (n = 6); and January 1996 to present (n = 20). The patients' charts were reviewed retrospectively. The incidence and type of vascular complications and patient and graft survival rates were analyzed. RESULTS: Although the demographics of the patients have not changed during the three phases of the living-donor liver transplant program, the outcomes have improved. Without the use of conduits, the incidence of portal vein complications has significantly decreased from 44% to 8%. The incidence of hepatic artery thrombosis has decreased from 22% to 0% with the use of microvascular techniques. The combined use of both techniques has led to a significant increase in graft survival, from 74% to 94%. CONCLUSIONS: The living-donor liver transplant recipient operation has undergone significant technical changes since its introduction in 1989. These changes have decreased the vascular complications associated with this type of graft. Avoiding the use of vascular conduits and performing microvascular hepatic artery anastomoses are the critical steps in improving graft survival.

Linear growth after pediatric liver transplantation.

To determine growth patterns in a large cohort of unselected children undergoing liver transplantation, the outcomes of 294 orthotopic liver transplantations performed in 221 children at The University of Chicago between October 1984 and October 1992 were retrospectively reviewed; 66% were alive at the time of this analysis. The mean age at transplantation was 4.1 +/- 5.0 years; 44% of the children were male and 16% of the transplants were from living-related donors. The mean height z score at the time of transplantation was -1.6 +/- 1.8, and 39% of children had height z scores of < -2.0 at transplantation. When children with growth retardation at the time of transplantation (height z scores of < -2. 0) were compared with children with more normal growth, there were no significant differences in gender or re-transplantation rates, although children with growth retardation at transplantation were significantly younger than those with more appropriate growth (2.8 +/- 4.1 years vs 4.7 +/- 5.1 years, P <.05). The height z score of all children with biliary atresia at the time of transplantation was -1.9 +/- 1.7 compared with -1.2 +/- 2.0 in those children with underlying diseases other than biliary atresia. Catch-up growth was seen in 37% to 47% of children at any given time point after transplantation. Children with evidence of catch-up growth (growth velocity z score >0) 2 years after transplantation were more likely to be first-time transplant recipients, had more growth retardation at the time of transplantation, and were receiving lower doses of prednisone at 2 years after transplantation. Younger children were most likely to demonstrate catch-up growth after transplantation. In summary, a large proportion of children have growth retardation at the time of liver transplantation. This growth retardation is inversely correlated with age. Before transplantation, children with biliary atresia grow less well than children with other forms of liver disease. Up to one half of children demonstrate catch-up growth after liver transplantation. Growth after transplantation is proportional to the degree of growth retardation at transplantation and inversely correlated to age at transplantation. Children with poor growth after transplantation are more likely to be receiving higher doses of corticosteroid.

Polyenylphosphatidylcholine inhibits PDGF-induced proliferation in rat hepatic stellate cells.

Polyenylphosphatidylcholine (PPC), a polyunsaturated phospholipid extract from soy beans, prevents the development of liver cirrhosis in animal models. Its mechanism of action is unknown. Based on the hypothesis that PPC might act by decreasing hepatic stellate cell proliferation, we studied the effect of PPC and its main components, dilinoleoylphosphatidylcholine (DLPC) and palmitoyl-linoleoylphosphatidylcholine (PLPC), on PDGF-induced stellate cell proliferation and intracellular signal transduction. Normal rat hepatic stellate cells in tissue culture were serumstarved, and incubated with 10ng/ml PDGF in the absence or presence of phospholipids. Cell proliferation was measured by 3H-thymidine incorporation. P44MAPK activation was determined by kinase assay, and AP-1 binding by electrophoretic mobility shift assay. PPC (200 ng/ml) significantly inhibited PDGF-induced proliferation (p < 0.05; ANOVA, n = 3) and antagonized PDGF-induced P44MAPK activation and AP-1 binding. This effect was mimicked by DLPC but not by PLPC. Neither DLPC nor PLPC prevented PDGF receptor activation. We conclude that PPC exerts a previously unrecognized effect on mitogen-induced stellate cell proliferation which may be mediated by DLPC. Inhibition of this cascade represents a potential mechanism for the inhibitory effect of PPC on hepatic fibrogenesis.

Bile acid stimulation of early growth response gene and mitogen-activated protein kinase is protein kinase C-dependent.

Hepatic stellate cells are exposed to elevated bile acid levels during hepatic injury and fibrogenesis. Upon activation, the stellate cell becomes a major effector cell during the development of hepatic fibrosis and cirrhosis. Bile acids may function as costimulatory signalling molecules. This hypothesis was tested in vitro using rat-derived hepatic stellate cells. Bile acids were studied at concentrations that occur during cirrhosis in vivo. Conjugated and unconjugated bile acids rapidly induced egr and fos gene expression as well as cytoplasmic mitogen-activated protein kinase (MAPK) activation. Protein kinase C was required for both egr induction and MAPK activation. These studies imply that bile acids could contribute to the perpetuation of hepatic fibrosis by helping to keep the stellate cell in an activated state.

Protein kinase C and mitogen-activated protein kinase are required for 1,25-dihydroxyvitamin D3-stimulated Egr induction.

Recent studies have demonstrated that 1,25-dihydroxyvitamin D3 (D3) can activate Raf kinase and induce Egr expression in cultured rat hepatic Ito cells (Lissoos, T. W., Beno, D. W. A., and Davis, B. H. (1993) J. Biol. Chem. 268, 25132-25138). Since Raf is an upstream activator of mitogen-activated protein kinase (MAPK), the current study evaluated the ability of D3 to activate MAPK. D3-activated MAPK and induced its cytoplasmic to perinuclear translocation in Ito cells. MAPK activation was found to be protein kinase C-dependent, which was analogous to previous studies of D3 and Raf activation. To further explore the D3 cascade, a series of transient transfections were performed using dominant negative raf and MAPK mutant plasmids which effectively block Ras-induced Raf and MAPK activity, respectively. D3 induced a marked increase in the expression of a chloramphenicol acetyltransferase reporter gene linked to the Egr promoter (egr-CAT). When the dominant negative Raf plasmid was co-transfected, there was no significant reduction in egr-CAT. In contrast, when the dominant negative MAPK plasmid was co-transfected, egr-CAT induction was completely abolished. These results suggest that 1) D3 stimulates MAPK via a protein kinase C-dependent pathway, 2) D3-induced Egr expression can occur via a pathway independent of Ras-induced Raf, and 3) D3 absolutely requires MAPK activity for Egr expression.

Successful control of endemic MRSA in a cardiothoracic surgical unit.

After a substantial increase in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the Cardiothoracic Surgical Unit at St. Vincent's Hospital, Sydney, a prospective study was undertaken in early 1986 to ascertain the carrier status of all patients entering the Unit. Of 84 patients, 27.4% were found to carry MRSA and the perineum was the major site of carriage, with 69.6% of MRSA positive cases carrying the organism in this site. As a result of these findings, the period of perioperative antibiotic cover was shortened, whole-body washing of patients with a 1% triclosan preparation was instituted and routine postoperative perineal swabs were taken. During the 18 months after implementation of these policies, a highly significant reduction in the number of MRSA carriers and infections was observed. The monitoring of perineal colonization proved to be a useful marker for increases in MRSA in the Unit.

Vibrio vulnificus septicaemia.

A patient, who had been receiving treatment for refractory anaemia with excess of myeloblasts for three years, developed septic shock due to Vibrio vulnificus septicaemia. The infection was believed to have been introduced with the ingestion of raw oysters. This organism is comparatively rare, but it can cause serious infection, and is known to be capable of very rapid tissue invasion.

Pasteurella ureae meningitis.

A 54-year-old man, with a history of alcohol abuse and previous skull fractures, developed a low-grade meningitis. The causative organism was Pasteurella ureae, an uncommon cause of bacterial infection, which has not been reported previously in Australia. The patient recovered after therapy with penicillin. A review of the cases of serious infection with this organism suggests that liver disease and skull trauma are common predisposing factors. Problems with the identification of P.ureae may be encountered unless its particular biochemical properties are recognized.

Serratia cross-infection in an intensive therapy unit.

During a 10-week period, 11 patients were involved in an outbreak of cross-infection with a non-pigmented strain of Serratia marcescens resistant to sulphonamides, trimethoprim, ampicillin, tetracycline, chloramphenicol, cephalexin, gentamicin, tobramycin, colistin, ticarcillin and kanamycin. The problem was confined to the intensive therapy areas of the hospital. The organism was apparently spread by a nursing sister who harboured it in a paronychial lesion. Prolonged carriage of S. marcescens was demonstrated. Methods of investigation of the outbreak and the measures adopted to terminate it are described.