No evidence of an additive inhibitory feeding effect following PP and PYY 3-36 administration.

Pancreatic polypeptide (PP) and peptide YY (PYY) are released by the gut in response to nutrients and inhibit food intake in rodents and humans. We hypothesized that PP and PYY(3-36) would inhibit feeding additively. Fasted male C57BL/6 mice were injected intraperitoneally with saline, PP, PYY(3-36) or PP+PYY(3-36) (n=7-10). Food intake at 1 h was significantly inhibited by 6 nmol kg(-1) PP and by 6 nmol kg(-1) PYY(3-36) (P<0.05) but not significantly following 3 nmol kg(-1) PP+3 nmol kg(-1) PYY(3-36). In a higher dose study 30 nmol kg(-1) PP, 30 nmol kg(-1) PYY(3-36) and 30 nmol kg(-1) PP+30 nmol kg(-1) PYY(3-36) all inhibited 1 h food intake compared with saline (P<0.05) but there was no significant difference in the food intake of the combined group compared with either hormone individually. Subsequently, 16 fasted lean healthy human volunteers (6 men and 10 women) received, in random order, 90 min intravenous infusions of saline, 4 pmol kg(-1)min(-1) PP, 0.4 pmol kg(-1)min(-1) PYY(3-36) and 4 pmol kg(-1)min(-1) PP+0.4 pmol kg(-1)min(-1) PYY(3-36). A pasta lunch was served 60 min following infusion. There was no evidence of a greater decrease in food intake with the combined PP+PYY(3-36) treatment (buffet meal energy intake (KJ): saline 2633+/-204, PP+PYY 2693+/-254, PP 2367+/-199, PYY 2511+/-196). These results suggest that PP and PYY(3-36) do not inhibit feeding additively in rodents or humans.

Ghrelin does not stimulate food intake in patients with surgical procedures involving vagotomy.

CONTEXT: Patients with gastric or esophageal surgery and transection of the vagus nerve may suffer from appetite and weight loss but without dysphagia or mechanical obstruction to eating. The gastric hormone ghrelin stimulates food intake and GH release in rodents and man. However, rodents with vagotomy are not sensitive to the feeding effects of ghrelin. OBJECTIVE: The objective of the study was to determine whether humans with vagotomy are sensitive to ghrelin. STUDY DESIGN: The design was a double-blind, randomized, placebo-controlled trial. SETTING: This was a hospital-based study. PATIENTS: Six men and one woman who all had a previous complete truncal vagotomy with lower esophageal or gastric surgery entered and completed the study. INTERVENTION: Each patient received 120-min infusions of saline, 1 pmol/kg.min ghrelin, and 5 pmol/kg.min ghrelin on 3 separate days. After 90 min, a buffet meal was served. MAIN OUTCOME MEASURE: Energy intake at the buffet meal was measured. RESULTS: Ghrelin-stimulated GH release in a dose-dependent manner was measured, confirming bioactivity. However, no change in energy intake was observed with either dose of ghrelin [energy intake (kilojoules): saline 2805 +/- 812; ghrelin 1 pmol/kg.min, 2486 +/- 767; ghrelin 5 pmol/kg.min, 2382 +/- 543; P = not significant]. CONCLUSIONS: Ghrelin is unlikely to be an effective appetite-stimulatory treatment for patients with vagotomy and esophageal or gastric surgery. Our results suggest that an intact vagus nerve may be required for exogenous ghrelin to increase appetite and food intake in man.

Controlling for socioeconomic confounding using regression methods.

STUDY OBJECTIVE: To describe the advantages of using Poisson regression methods as an alternative to standardisation when computing expected numbers of disease occurrences adjusted for possible confounding factors. The problem of assessing the adequacy of model fit when the expectations are small is addressed by analytical calculations and by simulation. The method is illustrated with data from the national register of childhood tumours. DESIGN: The tumour data are recorded in a national register. SETTING: England, Scotland, and Wales. SUBJECTS: The cases considered are all children registered with leukaemia or non-Hodgkin lymphoma under the age of 15 years between 1966-87. MAIN RESULTS: The methods show a significant variation of leukaemia incidence in relation to the Register General's standard region and a negative association with socioeconomic deprivation, as measured by the Townsend index. After allowing for these variables, the incidence seems to be reasonably homogeneous throughout the population, in the sense that the residual deviance does not seem to be much larger than would be expected by chance. CONCLUSIONS: The methods described have major advantages over standardisation in controlling for confounding, both in terms of flexibility of factor selection and assessment and also in the ability to determine whether there is residual variability of incidence after allowing for these factors.

Distribution of childhood leukaemias and non-Hodgkin's lymphomas near nuclear installations in England and Wales.

OBJECTIVE: To examine the relation between the risk of childhood leukaemia and non-Hodgkin's lymphoma and proximity of residence to nuclear installations in England and Wales. DESIGN: Observed and expected numbers of cases were calculated and analysed by standard methods based on ratios of observed to expected counts and by a new statistical test, the linear risk score test, based on ranks and designed to be sensitive to excess incidence in close proximity to a putative source of risk. SETTING: Electoral wards within 25 km of 23 nuclear installations and six control sites that had been investigated for suitability for generating stations but never used. SUBJECTS: Children below age 15 in England and Wales, 1966-87. MAIN OUTCOME MEASURE: Registration of any leukaemia or non-Hodgkin's lymphoma. RESULTS: In none of the 25 km circles around the installations was the incidence ratio significantly greater than 1.0. The only significant results for the linear risk score test were for Sellafield (P = 0.00002) and Burghfield (P = 0.031). The circles for Aldermaston and Burghfield overlap; the incidence ratio was 1.10 in each. One of the control sites gave a significant linear risk score test result (P = 0.020). All the tests carried out were one sided with P values estimated by simulation. CONCLUSION: There is no evidence of a general increase of childhood leukaemia or non-Hodgkin's lymphoma around nuclear installations. Apart from Sellafield, the evidence for distance related risk is very weak.

Subcutaneous administration of ghrelin stimulates energy intake in healthy lean human volunteers.

BACKGROUND: The gastric hormone ghrelin appears a useful agent to stimulate food intake in people with anorexia of illness. The loss of ghrelin's acyl group renders it inactive, thus it has been thought that subcutaneous administration may be problematic. OBJECTIVE: To investigate whether human subjects are sensitive to the effects of ghrelin administered by single subcutaneous injection. STUDY DESIGN: Randomized, double-blind, placebo-controlled trial. SUBJECTS: Sixteen healthy lean volunteers (eight men and eight women). PROTOCOL: Fasted subjects received subcutaneous injections of ghrelin (3.6 nmol/kg) or saline. After 30 min, a buffet breakfast was served. RESULTS: Ghrelin injection increased energy intake by 27% (ghrelin 5076 +/- 691 kJ versus saline 4230+/-607 kJ, P = 0.04). Ghrelin appeared to enhance the perceived palatability of the food offered (palatability score: ghrelin 81.1 +/- 3.6 versus saline 70.0 +/- 4.4; P = 0.03). CONCLUSIONS: These results suggest that subcutaneous ghrelin is effective at stimulating energy intake and improving palatability and may be of direct use in the treatment of appetite loss.

Gut and mind.

Obesity is a growing epidemic, causally associated with a number of serious medical conditions, including diabetes mellitus, coronary heart disease, and several cancers. The gut hormones ghrelin and peptide YY are secreted from the gut in response to changes to nutritional status. While food intake is stimulated by ghrelin, it is inhibited by peptide YY. The discovery, anatomy, and physiology of ghrelin and peptide YY are discussed, focusing on the adaptive changes in diseases such as obesity and anorexia nervosa. Ghrelin and PYY are important therapeutic targets in the quest to find an effective antiobesity treatment.