The actual, but not labelled, fat content of a soup preload alters short-term appetite in healthy men.

The effects of the actual and labelled fat content of a soup preload on appetite at a test meal 30 min later were assessed in 16 healthy men. Each participant ate lunch on four occasions, combining two levels of fat energy (Low, 265 kJ or High, 1510 kJ) and two types of label (Low-fat or High-fat), presented as fictitious soup brand names. Preliminary work established that the Low-fat labels produced an expectation of reduced fat content and lower anticipated hedonic ratings, whereas the High-fat labels generated expectations of a high-fat content and above average hedonic ratings. These expectancies were confirmed in the main experiment, with the soups labelled as high fat rated as both more pleasant and creamy than those labelled low-fat, independent of actual fat content. However, intake at the test meal was unaffected by the preload label, but instead reflected the actual fat (hence, energy) content of the soup, with significantly lower food intake after the high-fat soup regardless of the food label. Rated hunger was lower, and fullness higher, at the start of the meal after the high-fat preloads regardless of how they were labelled, while the pattern of appetite change during the test meal was unaffected by preload. These results suggest that realistic food labels can modify the immediate experience of a consumed food, but do not alter appetite 30 min later in healthy men.

Effects of test-meal palatability on compensatory eating following disguised fat and carbohydrate preloads.

OBJECTIVE: To test whether the palatability of a test meal altered compensatory eating following disguised high-energy fat and carbohydrate preloads. DESIGN: Effects of preload energy (low, 265 kJ, or high, 1510 kJ) and test-meal palatability (bland or palatable) were contrasted within-subjects, with a between-subjects contrast of fat and carbohydrate preloads. SUBJECTS: Twenty-four healthy, normal men (age 23.6+/-1.0 y, (body mass index) BMI 21.3+/-0.5). MEASUREMENTS: Microstructural analysis of test meal intake and rated appetite in the four test conditions, plus diary-based weighed intake analysis of energy intake post-lunch. RESULTS: Subjects ate significantly less at lunch after disguised high-energy fat or carbohydrate preloads relative to the low-energy preload, and ate significantly more of the palatable than bland lunch in all conditions. The reduction in eating following the high-energy preload was significantly less in the palatable condition. Intake post-lunch did not differ between conditions, and overall subjects had higher daily energy intake on the days they consumed the high-energy preloads. Rated hunger was significantly less 30 min after the high- than low-energy preloads, but increased on tasting the palatable food in all conditions. The high-energy preloads suppressed appetite immediately post-lunch. No differences between fat and carbohydrate were found on any measure. CONCLUSIONS: Manipulation of the palatability of a test meal modified the ability to respond to disguised high-energy preloads, with over-consumption most evident when disguised high-energy preloads were followed by a palatable food. Subsequent voluntary intake compensated for over-consumption of the palatable lunch, but not the high-energy preload.

Characteristics of general practices involved in undergraduate medical teaching.

BACKGROUND: The movement of medical education into the community has accelerated the development of a new model of general practice in which core clinical services are complemented by educational and research activities involving the whole primary care team. AIM: To compare quality indicators, workload characteristics, and health authority income of general practices involved in undergraduate medical education in east London with those of other practices in the area and national figures where available. DESIGN OF STUDY: A comprehensive survey of undergraduate and postgraduate clinical placements and practice-based research activity within general practice. SETTING: One-hundred and sixty-one practices based in East London and the City Health Authority (ELCHA). METHOD: Cross-sectional survey comparing routinely-collected information on practice resources, workload, income, and performance between teaching and non-teaching practices. RESULTS: In east London, teaching practices are larger partnerships with smaller list sizes, higher staff costs, and better quality premises than non-teaching practices. Teaching practices demonstrate significantly better performance on quality indicators, such as cervical cytology coverage and prescribing indicators. Patient-related health authority income per whole time equivalent (WTE) general practitioner (GP) is significantly lower among teaching practices. A multiple regression analysis was used to explore the association between teaching status and income. Eighty-eight per cent of the variation in patient-related income could be explained by the combination of list size, list turnover, removals at doctor's request, quality of premises, and immunisation and cytology rates. CONCLUSION: This study demonstrates that practice involvement in undergraduate education in east London is associated with higher scores on a range of organisational and performance quality indicators. The lower patient-related income of teaching practices is associated with smaller list sizes and may only be partially replaced by teaching income. Lower vacancy rates suggest that teaching practices are more attractive to doctors seeking partnerships in east London.

Barriers to the development of collaborative research in general practice: a qualitative study.

General practice-based research activity is increasing rapidly, particularly for large, collaborative, multi-centre studies. We conducted semi-structured interviews with general practitioners and other professionals at practices in the East London and the City Health Authority area, to investigate the difficulties presented by becoming involved in these studies. Interviewees' main concerns were: time constraints; team motivation; the perception that external researchers have unrealistic expectations; the need for good communications throughout and, specifically, for good feedback from these researchers.

Linking general practices to the medical schools: qualitative issues.

The University Linked Practices (ULP) programme links general practices involved in undergraduate medical education with computer services provided through the school of medicine and dentistry. In-depth interviews were conducted with 26 staff involved in teaching undergraduate medical students in 15 general practices across east London and Essex. The interview schedule focused on the use of the computer, IT experience and training needs and the use of the computer network as a resource in undergraduate teaching. It is important to work with curriculum planners to ensure that computers are fully integrated into new courses.

Why? What? and How? IT provision for medical students in general practice.

OBJECTIVES: The aim of this paper is to discuss the increasing use of computers in undergraduate medical education and explore the why, what and how of providing IT facilities to undergraduate medical students when they are on placement in general practice. Adequate computing facilities are usually available within hospitals and medical schools, however, major changes are taking place in undergraduate education resulting in more teaching being undertaken in the community. Students will therefore need access to comparable facilities whilst in primary care settings in order for their training not to be compromised. SETTING: This paper describes one initiative addressing this need: the University Linked Practices (ULP) project in the Department of General Practice and Primary Care at St. Bartholomew's and the Royal London School of Medicine and Dentistry. DESIGN: We discuss the ways in which computers are currently being used in medical education and discuss some of the merits and drawbacks that are associated with this increasing drive to computerization.

Maltodextrin preloads reduce food intake without altering the appetiser effect.

The effects of consumption of a soup preload with added maltodextrin, relative to a no-maltodextrin control soup matched for sensory properties, on intake and the pattern of changes in rated hunger and fullness during lunch were investigated in 24 male volunteers. Preloads were consumed 30 min before lunch and condition-order counterbalanced. Intake at lunch was reduced significantly by 77 g (407 kJ) after the maltodextrin preload, and this reduced intake was associated with a significant reduction in eating rate but not meal duration. Hunger ratings were significantly lower, and fullness ratings significantly higher, at the start of lunch after the maltodextrin compared with control preload. However, the pattern of changes in subjective appetite once eating had started (assessed by analyzing best-fit quadratic functions between rated appetite and actual intake) did not differ between preloads. Neither the rated pleasantness of the lunch food at the start of the test meal nor the pattern of change in pleasantness across the meal differed between preloads. These results imply that the effect of maltodextrin preloads on appetite is to reduce the general desire to eat, and possible mechanisms for this effect are discussed.

Independent effects of palatability and within-meal pauses on intake and appetite ratings in human volunteers.

The effects of the introduction of timed pauses within meals and palatability on food intake and changes in rated appetite during a meal were assessed in three experiments in which volunteers ate a lunch of pasta with a tomato sauce. Eating was monitored using a disguised electronic balance attached to a micro-computer, which also allowed the introduction of timed pauses within meals. In the first experiment, 16 subjects were tested with both a bland and palatable food (with 0.27% oregano), with eating uninterrupted or with pauses after every 50 g consumed during which appetite ratings were completed. Both the addition of oregano and the introduction of regular within-meal pauses enhanced overall intake. Rated hunger increased in the early stages of eating the palatable food in the interrupted condition, and then declined, whereas hunger declined throughout with the bland food. Similarly, the linear function relating intake to time in the uninterrupted condition was greater with the palatable food. In the second experiment, nine subjects ate the palatable food with no pauses within meals, with 30-second pauses with appetite ratings or with 30-second pauses in a non-appetite task. Intake was greater in both pause conditions than when eating was uninterrupted. In Experiment 3, the effect of pause duration was investigated in a further 16 subjects, with either no pause or a pause of 5, 30 or 60 seconds. Subjects ate more in all pause conditions than with no pauses, while ratings of hunger and fullness suggested that subjects were less satisfied at the end of the meal with longer pauses. These data confirm previous work which suggests that palatability exerts its effect by stimulating appetite and eating rate, but also suggest that the introduction of pauses within meals enhances intake as well, contradicting the idea that pausing within meals should reduce intake by allowing more time for post-ingestive satiety to develop.

Effects of naltrexone on food intake and changes in subjective appetite during eating: evidence for opioid involvement in the appetizer effect.

The effects of 50 mg naltrexone on eating and subjective appetite were assessed in a double-blind placebo-controlled study with 20 male volunteers. Appetite was monitored using a disguised digital balance connected to a micro-computer, which constantly monitored the amount of food remaining, and which automatically interrupted feeding for 30 s after every 50 g consumed to allow appetite ratings to be made. Half the subjects ate pasta with a cheese sauce, and the remainder pasta with a tomato sauce. Subjects ate significantly less of both foods after 50 mg naltrexone than in either the placebo condition or on the initial (familiarisation) day. Naltrexone also reduced the rated pleasantness of both foods, and reduced overall eating rate. When best-fit quadratic functions were used to describe changes in rated hunger in relation to intake within the meal, naltrexone abolished the positive linear component reflecting the initial stimulation of appetite without altering either intercept or the negative quadratic function. Although mood ratings suggested that naltrexone had a mild sedative effect, mood changes alone could not explain the effects of naltrexone on appetite. Overall, these data suggest a specific role for opioids in the stimulation of appetite through palatability.

Selective effects of naltrexone on food pleasantness and intake.

The effects of 50 mg naltrexone on both pleasantness and intake of 10 common food items were investigated using a double-blind placebo-controlled study with 16 male volunteers. Rated food pleasantness was reduced significantly in the naltrexone condition compared with both controls (placebo and baseline). However, pleasantness ratings were not affected uniformly across foods, with sweetened, fatty, and high-protein foods being most affected. Changes in rated unpleasantness generally mirrored those for pleasantness, but evaluations of saltiness and sweetness were unaffected by naltrexone. Although total intake was reduced in the naltrexone condition, this was not significant compared with placebo. However, fat and protein intakes were significantly less following naltrexone. The effect of naltrexone on intake was also food dependent, but in this case intake of sweet foods was spared relative to other food categories. The apparent discrepancy between liking and intake data with sweet foods could be interpreted in terms of the likely influence of normal eating styles on food selection during a buffet-style meal, and may explain some contradictions in previous studies of this kind. The implications for understanding opioid involvement in food acceptability are discussed.

d-fenfluramine's effects on normal ingestion assessed with taste reactivity measures.

The effects of d-fenfluramine on intake and on hedonic responses to taste stimuli in rats were investigated using a modified taste reactivity paradigm. Subjects (n = 15) were first trained to consume a 3% sucrose solution. They were then pretreated with d-fenfluramine (0.3-3.0 mg/kg, i.p.), and tested with access to either 3% sucrose, or a 0.01% quinine HCl solution. In the modified taste reactivity test, chronic oral cannulation was not used; instead, taste reactivity measures were scored during periods of noningestion in a voluntary intake test. d-Fenfluramine reliably reduced both sucrose and quinine consumption, and increased latency to drink at the highest dose. d-Fenfluramine also spared aversive responses to quinine, but reduced positive ingestive responses to sucrose. These results are consistent with an effect of d-fenfluramine to reduce taste palatability, which may, in turn, be an important factor in the effect of this drug on feeding motivation.

25-hydroxycholecalciferol in poultry nutrition.

Vitamin D is a complex of secosteroids that must undergo metabolic alterations to reach optimal biological activity. The parent compounds 1) ergocalciferol (D2) and 2) cholecalciferol (D3) can be synthesized in the leaves of many plants or in the skin of most animals, respectively. Transport of vitamin D steroids after absorption is associated with vitamin D binding proteins (DBP). In general, the relative binding affinities of the vitamin D steroids are: 25-hydroxy vitamin D3 [25-(OH)D3] = 24,25-dihydroxy vitamin D3 [24,25-(OH)2D3] = 25,26-dihydroxy vitamin D3 [25,26-(OH)2D3] > 25-hydroxy vitamin D2 (25-(OH)D2) > 1,25-dihydroxy vitamin D3 [1,25-(OH)2D3] > vitamin D3. The DBP in poultry does not bind D2 forms effectively, and therefore poultry can not use this form of vitamin D adequately. The concentration of 25-(OH)D3 in blood seems to be well correlated with dietary vitamin D intake or exposure to ultraviolet light. The 1 alpha hydroxylase enzyme in the kidney is subject to negative feedback regulation and is critical for formation of the active metabolite 1,25-(OH)2D3. The intracellular vitamin D receptor (VDR) specifically binds 1,25-(OH)2D3 and is necessary for cellular action. Increased levels of two to three orders of magnitude are required for 25-(OH)D3 to compete with 1,25-(OH)2D3 for binding on VDR. Feeding studies with 25-(OH)D3 suggest it has nearly twice the activity of vitamin D3. Hatchability studies have shown that 25-(OH)D3 supports good fertility and hatchability, whereas hens fed only 1,25-(OH)2D3 did not have normal hatchability. Likewise, 1,25-(OH)2D3 seems to reach toxic levels at dietary concentrations only two to three times optimal dietary levels whereas feeding 25-(OH)D3 for extended periods at levels 8 to 10 times requirement seems to have no adverse effects. It seems that 25-(OH)D3 is the most active metabolite of vitamin D3, ultimately capable of supporting both cellular functions and embryonic development in chickens and turkeys when fed as the sole source of vitamin D3.

Benzodiazepines and palatability: taste reactivity in normal ingestion.

The taste reactivity (TR) test was devised as a method to obtain behavioural data in response to gustatory stimuli in neurologically impaired rats, incapable of voluntary feeding. Sapid solutions were infused through surgically implanted intraoral cannulae. Facial and motor responses corresponded well to known hedonic and aversive properties of tastes (e.g., sweet, bitter). TR testing has since proved effective as an adjunct to intake-based methods, in the psychopharmacology of ingestion in the normal rat. We developed a nonsurgical modification of the TR test, in which intact rats sampled stimuli voluntarily. The benzodiazepine receptor agonist midazolam (3.0 mg/kg, IP) was administered to rats first trained to consume a sweet 3% sucrose solution, and later tested with access to a bitter 0.01% quinine solution. Response were videotaped, and TR measures were scored during periods of noningestion using a frame-by-frame playback. Treatment increased ingestion and facilitated ingestive responses in accordance with published data for cannulated rats. Results support a two-component view of response palatability, in which treatment alters feeding motivation, increasing positive palatability and facilitating ingestion of both palatable and unpalatable stimuli.

Safety of 25-hydroxycholecalciferol as a source of cholecalciferol in poultry rations.

We conducted two safety studies of 25-hydroxycholecalciferol [25(OH)D3] in poultry broilers at levels ranging from 1 to 200 times those commonly used for cholecalciferol (vitamin D3) supplementation in the industry. In the first experiment, 1-d-old male and female broiler chickens were fed commercial diets containing either vitamin D3 or 25(OH)D3 at concentrations of 69, 207, and 690 micrograms of 25(OH)D3/kg of feed. The second experiment compared effects of 25(OH)D3 and vitamin D3 on performance and survival of broilers at levels ranging from 1 to 200 times the basal level of 69 micrograms/kg feed. When 25(OH)D3 was fed in equal amounts (wt/wt) to vitamin D3, there was an increase in body weight and a decrease (improvement) in adjusted feed efficiency in both experiments, but the changes were significant only in the first experiment. In the first experiment, serum 25(OH)D3 concentrations increased from 13.3 +/- 4.3 to 42.5 +/- 18 ng/mL in birds fed vitamin D3 or 25(OH)D3, respectively, and rose to 246 +/- 38 ng/mL in birds fed the highest level of 25(OH)D3. Tissue 25(OH)D3 concentrations were much lower than serum concentrations and were highly correlated to the latter, regardless of dietary treatment. In Experiment 2, there was some evidence of renal calcification in birds fed 25(OH)D3 at 10 times the basal level, whereas dietary levels of vitamin D3 of 50 times the basal level were required to show some evidence of renal calcification. On the basis of both renal calcification and body weight, the present studies would suggest that 25(OH)D3 is 5 to 10 times more toxic than vitamin D3.

Comparison of dietary 25-hydroxycholecalciferol and cholecalciferol in broiler chickens.

We conducted a series of 10 feeding trials involving over 36,000 broilers. The effects of various dietary levels of cholecalciferol (vitamin D3) or 25-hydroxycholecalciferol (25-OH-D3) were compared using a "basal" dosage level of 69 micrograms/kg feed, as well as levels ranging from .5 to 1.5 times the basal level. For all 10 studies, average body weight increased by an average of .042 +/- .03 kg (P < .001) and adjusted feed efficiency decreased (improved) by an average of .026 +/- .0046 kg/kg (P < .001) in birds fed 25-OH-D3 in comparison to those fed vitamin D3 at the basal level. Changes in mortality were not detected. Evaluation of different dietary levels of 25-OH-D3 revealed a significant dose-response relationship, with maximal effects on weight gain, feed efficiency, and breast meat yield being observed in the range of 50 to 70 micrograms/kg feed. Preliminary studies with different levels of vitamin D3 suggested no additional benefits on weight gain or feed efficiency with higher dietary levels of vitamin D3. Serum 25-OH-D3 concentrations increased more rapidly in birds fed 25-OH-D3 than in birds fed vitamin D3. There were significant correlations with body weight, feed conversion, and serum 25-OH-D3 concentrations, with no correlations observed between serum 1,25-(OH)2D3 concentrations and these variables.

Femoral abnormalities and vitamin D metabolism in X-linked hypophosphatemic (Hyp and Gy) mice.

X-linked hypophosphatemia is a genetic bone disease in humans and mice. Two closely linked mutations in mice, Hyp and Gy, cause low plasma phosphate and a rachitic and osteomalacic bone disease. Because of the controversy as to whether Gy is a good model for X-linked hypophosphatemia, the phenotypic severity of these two mutations was compared in both sexes and on two genetic backgrounds. The depression in plasma levels of phosphate was similar in all 10-week-old mutant mice. Male Hyp mice and heterozygous female Hyp mice were affected with similar severity in terms of reduced tail growth, shortened femora, reduced femoral mineral content, and abnormal mineral composition of the femoral matrix. In contrast, male Gy mice did not survive on the C57BL/6J background and were more severely affected than female Gy mice on the B6C3H background. The hybrid B6C3H background ameliorated the bone disease compared with the inbred C57BL/6J background for both mutant strains. There was no evidence of change in the plasma levels of 1,25-dihydroxyvitamin D, duodenal level of vitamin D-dependent calcium-binding protein, or urinary level of calcium in these adult mutant mice. In summary, Gy mice have a sexual dimorphism not present in Hyp mice. These two genes may indicate the presence of multiple gene loci in the human disease, with multiple proteins involved in the pathophysiology of the bone disease.

Response of jejunal phosphate absorption to 1,25-dihydroxyvitamin D(3) stimulationin vivo in young X-linked hypophosphatemic (Hyp) mice.

YoungHyp mice malabsorb phosphate from the jejunum at 4 weeks of age. This has been attributed to both low plasma levels of 1,25-dihydroxyvitamin D and to intestinal resistance to stimulation by 1,25-dihydroxyvitamin D. To differentiate between these two hypotheses, 4 week old normal andHyp mice were treated with 0, 17, 50, or 150 ng/kg/day of 1,25-dihydroxyvitamin D(3) by Alzet osmotic mini pumps (n=10-12/group). After 4 days, the jejunum was isolated by sutures and 0.5 ml 2 mM Na(2)HPO(4) in 150MM: NaCl with 1.0 µCi(32)PO(4) was injected into the lumen. After 8 min, plasma, jejunal tissue and lumenai contents were measured for(32)P content. Absorption was measured as counts removed from the lumen. Both normal andHyp mice responded to the 1,25-dihydroxyvitamin D(3) with increased absorption, increased tissue(32)P and increased plasma(32)P.Hyp mice responded less than normal mice to the 50 ng/kg/day dose in plasma(32)P levels (significant dose by genotype interaction,P<0.05). Plasma was pooled by genotype and dose for the measurement of plasma 1,25-dihydroxyvitamin D. This yielded 13 samples (7 normal and 6Hyp). Absorption of(32)P (r=0.75, p=0.002) and jejunal tissue content of(32)P (r=0.66, p=0.02) were correlated to plasma 1,25-dihydroxyvitamin D. Analysis of covariance revealed a significant difference in phosphate absorption between normal andHyp mice (p=0.02). In conclusion, there is a partial resistance of intestinal phosphate absorption to 1,25-dihydroxyvitamin D stimulation.

Regulated production and intracrine action of 1,25-dihydroxyvitamin D3 in the chick myelomonocytic cell line HD-11.

To better understand the extrarenal production of active vitamin D metabolites by cells of the monocyte/macrophage lineage, we investigated the 25-hydroxyvitamin D (25OHD)-1-hydroxylation reaction in the v-myc-transformed chick myelomonocytic cell line HD-11; the 1-hydroxylation reaction in this cell line has a high affinity for 25-hydroxylated vitamin D substrates, is localized to mitochondria, and is associated with cytochrome P450 activity. In this study we demonstrated that the HD-11 cell 1-hydroxylation reaction in vitro is not affected by the majority of extracellular regulatory factors that modulate expression of the renal 25OHD-1-hydroxylase in vivo. A 50% increase in extracellular calcium and phosphate concentrations, physiological inhibitory events for renal 1,25-dihydroxyvitamin D [1,25-(OH)2D] synthesis, did not decrease basal expression of the HD-11 cell 1-hydroxylation reaction, nor did a 50% decrease in extracellular calcium and phosphate concentrations, stimulatory signals for the 1-hydroxylase in vivo, increase 1,25-(OH)2D3 synthesis in vitro. Receptor-saturating concentrations of PTH and PTH-related peptide were similarly without effect. In contrast, the HD-11 1-hydroxylation reaction was significantly stimulated in a dose-dependent fashion by the macrophage stimulatory agents lipopolysaccharide [P < 0.001 at a maximum effective concentration (EC100) of 25 micrograms/ml] and interferon-gamma (P < 0.001 at EC100 of 1000 IU/ml) and by insulin-like growth factor-I (P < 0.01 at EC100 of 15 nM) with the rank order of stimulation being interferon-gamma > lipopolysaccharide > insulin-like growth factor-I. Dexamethasone (> or = 10 nM) and the cytochrome P450 inhibitors (EC100, 20 microM), ketoconazole, clotrimazole, and menadione, all significantly inhibited the HD-11 cell 1-hydroxylation reaction. The naphthoquinone menadione, which blocks electron transfer to the P450-associated enzyme, was the most effective inhibitor of the reaction in both intact cells (3 +/- 1% of basal expression; P < or = 0.002) and after reconstitution of HD-11 cell mitochondrial extracts with a ferredoxin, reductase, O2, and NADPH (5 +/- 1% of basal; P < or = 0.02). We have also shown that 1,25-(OH)2D3 produced from substrate 25OHD3 appears to exert an endogenous (intracrine) inhibitory effect on HD-11 cell growth; incubation of HD-11 cells with a concentration of ketoconazole (10 microM) known to reduce 1,25-(OH)2D3 production by roughly 50% restored 50% of the growth deficit induced by 1,25-(OH)2D3 (EC100, 100 nM).(ABSTRACT TRUNCATED AT 400 WORDS)