Balancing training and outcomes in total knee replacement: A ten-year review.

INTRODUCTION: 10-year study examining differences in total knee arthroplasty (TKA) functional outcomes and survivorship in patients operated on by consultant and trainee orthopaedic surgeons. METHOD: Data was prospectively collected from all elective TKAs performed at our three linked institutions. Patient demographics, surgeon grade, and length of hospital stay were recorded. Outcomes pre-operatively and at 1, 3, 5, 7 and 10 years included mortality, need for revision surgery and function as documented by the patients' Knee Society Score. RESULTS: 686 patients were included in the study. 450 (65.5%) patients were operated by consultant surgeons and 236 (34.4%) by trainees. On multivariate analysis no significant differences were observed between groups in length of hospital stay (p = 0.695), implant survival (p = 0.422), and function (p = 0.507) at 10 years. On Cox regression analysis no significant difference was observed in mortality (p = 0.209) at 10 years. 4 patients over this time period were lost to formal follow up. CONCLUSION: No significant difference was observed in the TKA outcomes between consultants and trainees 10 years post-operatively.

The effect of dietary energy:protein ratio, protein quality and food allocation on the efficiency of utilisation of protein by broiler chickens.

1. Various theories have been proposed to explain the reduced performance of broilers when given feeds excessively high in protein, but a satisfactory solution to this problem had, up to now, not been found. Three experiments were conducted to test the hypothesis that the efficiency of utilisation of protein (ep) is a linear-plateau function of the ratio between the feed apparent metabolisable energy and digestible crude protein contents (AMEn:DCP) and that dietary protein quality, feed allocation and sex do not influence this relationship. 2. A 'linear-plateau' model successfully described the efficiency of protein utilisation (ep) as a function of AMEn:DCP in all three experiments. In Experiment 1, with both sexes being both ad libitum and control fed, the breakpoint was at 58.6 MJ AMEn/kg DCP. In Experiment 2, both sexes were fed balanced and unbalanced protein series, and at different rates, the slopes of the ascending part of the linear-plateau relationships for the different treatments were the same for all treatments (0.0204), and the inflection point was at 71 MJ AMEn/kg DCP. Using similar treatments in Experiment 3, the breakpoint for the balanced protein was 72 MJ/kg and for the unbalanced, 64, with a combined slope of 68 MJ AMEn/kg DCP. 3. The three experiments provide adequate evidence that ep is a linear-plateau function of the dietary AMEn:DCP ratio with a breakpoint of around 66.2 ± 1.98 MJ AMEn/kg DCP. Below this critical ratio, food intake declines as does protein and lipid retention. 4. That broilers, like pigs, exhibit an energy-dependent phase when high-protein feeds are offered is of practical importance when formulating pre-starter feeds for broilers and starter feeds for turkey poults as the ep of such feeds may well fall below the maximum due to the lack of dietary energy required to process the high dietary protein contained in such feeds resulting in poorer performance than expected.

Ethics, Evidence Based Sports Medicine, and the Use of Platelet Rich Plasma in the English Premier League.

The use of platelet rich plasma (PRP) as a novel treatment is discussed in the context of a qualitative research study comprising 38 interviews with sports medicine practitioners and other stakeholders working within the English Premier League during the 2013-16 seasons. Analysis of the data produced several overarching themes: conservatism versus experimentalism in medical attitudes; therapy perspectives divergence; conflicting versions of appropriate evidence; subcultures; community beliefs/practices; and negotiation of medical decision-making. The contested evidence base for the efficacy of PRP is presented in the context of a broader professional shift towards evidence based medicine within sports medicine. Many of the participants while accepting this shift are still committed to casuistic practices where clinical judgment is flexible and does not recognize a context-free hierarchy of evidentiary standards to ethically justifiable practice. We also discuss a tendency in the data collected to consider the use of deceptive, placebo-like, practices among the clinician participants that challenge dominant understandings of informed consent in medical ethics. We conclude that the complex relation between evidence and ethics requires greater critical scrutiny for this emerging specialism within the medical community.

Transient radio bursts from rotating neutron stars.

The radio sky is relatively unexplored for transient signals, although the potential of radio-transient searches is high. This was demonstrated recently by the discovery of a previously unknown type of source, varying on timescales of minutes to hours. Here we report a search for radio sources that vary on much shorter timescales. We found eleven objects characterized by single, dispersed bursts having durations between 2 and 30 ms. The average time intervals between bursts range from 4 min to 3 h with radio emission typically detectable for <1 s per day. From an analysis of the burst arrival times, we have identified periodicities in the range 0.4-7 s for ten of the eleven sources, suggesting origins in rotating neutron stars. Despite the small number of sources detected at present, their ephemeral nature implies a total Galactic population significantly exceeding that of the regularly pulsing radio pulsars. Five of the ten sources have periods >4 s, and the rate of change of the pulse period has been measured for three of them; for one source, we have inferred a high magnetic field strength of 5 x 10(13) G. This suggests that the new population is related to other classes of isolated neutron stars observed at X-ray and gamma-ray wavelengths.

WITHDRAWN: Non-aspirin, non-steroidal anti-inflammatory drugs for treating osteoarthritis of the knee.

BACKGROUND: Osteoarthritis(OA) is the most common rheumatic disease. Simple analgesics are now accepted as the appropriate first line pharmacological treatment of uncomplicated OA. Non-aspirin NSAIDs are licensed for the relief of pain and inflammation arising from rheumatic disease. OBJECTIVES: To determine whether there is a difference in the relative efficacy of individual non-steroidal anti-inflammatory drugs (NSAIDs) when used in the management of osteoarthritis (OA) of the knee. SEARCH STRATEGY: We searched Medline (1966-1995) and Bids Embase (Jan-Dec, 1980-1995). The searches were limited to publications in the English language, and were last performed in November 1996. We used modified Cochrane Collaboration search strategy to identify all randomised controlled trials. The MeSH heading "osteoarthritis" was combined with the generic names of the 17 non-aspirin NSAIDs licensed in the UK for the management of OA in general practice. The search of Embase used the term "osteoarthritis" if present in the abstract, title or keywords, and was combined with the generic names of the 17 non-aspirin NSAIDs, only if they were mentioned in the title, abstract or keywords. SELECTION CRITERIA: All double blind, randomised controlled trials, in the English language, comparing the efficacy of two non-aspirin NSAIDs in the management of osteoarthritis of the knee, were selected. Only trials with subjects aged 16 years and over, with clinical and/or radiological confirmation of the diagnosis of OA knee were included. Studies which compared one "trial" NSAID with one "reference" NSAID were included provided they were non-aspirin NSAIDs available in the UK and were licensed for the treatment of OA by general practitioners. Trials which were placebo-controlled and which also involved the comparison of two NSAIDs were also included. DATA COLLECTION AND ANALYSIS: The methodological design of each study was scored according to a pre-determined system. The three main outcome measures of pain, physical function and patient global assessment were chosen based on the core set agreed upon by OMERACT (Outcome Measures in Rheumatology Clinical Trials). These were used to determine the power of each trial. The equivalency of NSAID doses was calculated using the percentage of the recommended maximum daily dose. Sample size estimates for the detection of clinically relevant changes in outcome measures used in the assessment of OA knee were used for power calculations. These calculations were performed to determine whether the trials were of a sufficient size to detect clinically relevant differences which were statistically significant. The calculations incorporate estimates of standard deviation, and minimum, median and maximum differences (delta) between drugs which are deemed to be clinically important. The number of "withdrawals due to lack of efficacy" was also selected as an outcome measure for this review. The Peto odds ratio and 95% confidence intervals were calculated where possible. The results of studies which compared the same trial and reference NSAIDs were combined where possible. MAIN RESULTS: Of the 1151 trials identified by the search strategy, 22 involved knee osteoarthritis only. Sixteen of these trials fulfilled the inclusion criteria and were entered in the review. Eight NSAIDs were represented in these trials. Etodolac was represented in 11 trials. The reference NSAID in these trials was piroxicam (n=3), naproxen(n=3), diclofenac (n=3), indomethacin (n=1), and, nabumetone (n=1). The reported methodological design of the trials was poor, with a median score of 3 (out of a maximum of 8). The results of the trials comparing the same trial and reference NSAIDs were pooled for the outcome "withdrawal due to lack of efficacy". For the comparison, etodolac versus piroxicam, the odds ratio favoured etodolac i.e. patients receiving etodolac were less likely to withdraw due to lack of efficacy. The dose of etodolac used in each of these three studies, however, was greater than the corresponding dose of piroxicam (based on percentage maximum daily dose). The significance of these results is therefore questionable. For the comparisons etodolac versus diclofenac, and etodolac versus naproxen, there were no clear differences between treatments. In one study [Bellamy 1993], a statistically significant difference was detected between treatments with regard to withdrawals due to lack of efficacy. In this trial, which compared equivalent NSAID doses, diclofenac was the favoured NSAID compared to tenoxicam(p=0.04). Two studies showed a statistical difference in patient global assessment of condition, which favoured the trial NSAID. In both cases the trial NSAID was etodolac, used in doses approximately 25-44% greater than the reference NSAID. Two studies showed a statistically significant difference in pain relief between NSAIDs. The trial NSAID in both cases was again etodolac but the doses exceeded those of the reference NSAIDs. AUTHORS' CONCLUSIONS: In spite of the large number of publications in this area, there are few randomized controlled trials. Furthermore, most trials comparing two or more NSAIDs suffer from substantial design errors. From the results of this review it is concluded that no substantial evidence is available related to efficacy, to distinguish between equivalent recommended doses of NSAIDs. Had studies employed appropriate doses of comparator drug, most would have been sufficiently powerful to detect clinically important differences in efficacy. As differences in efficacy between NSAIDs have not been recorded, the selection of an NSAID for prescription for OA knee should be based upon relative safety, patient acceptability and cost.

Do trainee surgeons have an adverse effect on the outcome after total hip arthroplasty?: a ten-year review.

AIMS: The long-term functional outcome of total hip arthroplasty (THA) performed by trainees is not known. A multicentre retrospective study of 879 THAs was undertaken to investigate any differences in outcome between those performed by trainee surgeons and consultants. PATIENTS AND METHODS: A total of 879 patients with a mean age of 69.5 years (37 to 94) were included in the study; 584 THAs (66.4%) were undertaken by consultants, 138 (15.7%) by junior trainees and 148 (16.8%) by senior trainees. Patients were scored using the Harris Hip Score (HHS) pre-operatively and at one, three, five, seven and ten years post-operatively. Surgical outcome, complications and survival were compared between groups. The effect of supervision was determined by comparing supervised and unsupervised trainees. A primary univariate analysis was used to select variables for inclusion in multivariate analysis. RESULTS: There was no evidence that the grade of the surgeon had a significant effect on the survival of the patients or the rate of revision (p = 0.987 and 0.405, respectively) up to 12 years post-operatively. There was no significant difference in post-operative functional HHS or total HHS among consultants, junior and seniors up to ten years post-operatively (p = 0.401 and 0.331), respectively. There was no significant difference in hospital stay (p = 0.855) between different grades of surgeons. There was no evidence that the level of supervision had an effect on the survival of the patients or the rate of revision (p = 0.837 and 0.203, respectively) up to 12 years post-operatively. There was no significant difference between supervised and unsupervised trainee groups in post-operative functional HHS or total HHS up to ten years post-operatively (p = 0.213 and 0.322, respectively). There was no significant difference in the mean hospital stay between supervised and unsupervised trainees (p = 0.908). TAKE HOME MESSAGE: This study suggests that when trainees are appropriately supervised, they can obtain results comparable with those of their consultant colleagues when performing THA.

The presence of cellular metabolites in milk.

Cellular metabolites are present in goats' milk. The concentrations of UDPgalactose and some nucleotides were higher in milk than in mammary tissue. Other metabolites were present in milk at similar concentrations to those found in the mammary gland. It is proposed that the concentrations of these metabolites in milk reflect their Golgi-vesicular and cytosolic concentrations.

Some effects of glucose concentration and anoxia on glycolysis and metabolite concentrations in the perfused liver of fetal guinea pig.

Effects of glucose concentration and anoxia upon the metabolite concentrations and rates of glycolysis and respiration have been investigated in the perfused liver of the fetal guinea pig. In most cases the metabolite concentrations in the perfused liver were similar to those observed in vivo. Between 50 days and term there was a fall in the respiratory rate and in the concentration of ATP and fructose 1,6-diphosphate and an increase in the concentration of glutamate, glycogen and glucose. Reducing the medium glucose concentration from 10 mM to 1 mM or 0.1 mM depressed lactate production and the concentration of most of the phosphorylated intermediates (except 6-phosphogluconate) in the liver of the 50-day fetus. This indicates a fall in glycolytic rate which is not in accord with the known kinetic properties of hexokinase in the fetal liver. Anoxia increased lactate production by, and the concentrations of, the hexose phosphates ADP and AMP in the 50-day to term fetal liver, while the concentration of ribulose 5-phosphate, ATP and some triose phosphates fell. These results are consistent with an activation of glycolysis, particularly at phosphofructokinase and of a reduction in pentose phosphate pathway activity, particularly at 6-phosphogluconate dehydrogenase. The calculated cytosolic NAD+/NADH ratio for the perfused liver was similar to that measured in vivo and evidence is presented to suggest that the dihydroxyacetone phosphate/glycerol 3-phosphate ratio gives a better indication of cytosolic redox than the lactate/pyruvate ratio. The present observations indicate that phosphofructokinase hexokinase and possibly pyruvate kinase control the glycolytic rate and that glyceraldehyde-3-phosphate dehydrogenase is at equilibrium in the perfused liver of the fetal guinea pig.

Effects of glucagon and alpha- and beta-agonists on glycogenolysis and gluconeogenesis in isolated ovine hepatocytes.

(1) The effects of glucagon, dibutyryl cyclic AMP, vasopressin, phenylephrine, and isoproterenol on glycogenolysis and gluconeogenesis were investigated using isolated ovine hepatocytes. (2) Glycogenolysis was stimulated by all effectors except vasopressin. The response to alpha-agonists was greater than that of beta-agonists in older animals. Stimulation by beta-agonists increased after 30 h primary culture. (3) Gluconeogenesis from propionate or L-lactate plus pyruvate was stimulated to a small extent by dibutyryl cyclic AMP, glucagon and isoproterenol but not by vasopressin or phenylephrine. (4) No effects of lactation were observed. (5) Data are compared to results obtained in other species and the physiological significance of the results in relation to the ruminant is discussed.

The effects of concanavalin A on milk secretion and mammary metabolism in the goat.

The effects of concanavalin A on the rate of milk secretion and the concentration of metabolites in milk were studied following intramammary injection of the lectin via the teat canal into one mammary gland of lactating goats. Concanavalin A decreased milk secretion from the treated gland, reduced the concentrations of phosphoenolpyruvate, nucleoside diphosphate and 2-oxoglutarate in milk and increased the concentrations of glucose, galactose, glycerol, L-lactate, pyruvate, isocitrate and citrate. The changes in the concentrations of the metabolites in milk are discussed in relation to biochemical changes occurring in the mammary gland during the suppression of milk secretion. It is suggested that, when lactose synthesis and secretion is decreased, substantial metabolism of glucose via glycolysis occurs.

L-Lactate as a source of carbon for fatty acid synthesis in adult and foetal sheep.

The contribution of carbon from acetate, glucose and L-lactate to fatty acid synthesis has been compared in adipose tissue from adult and foetal sheep. Adipose tissue slices were incubated with mixtures of acetate, glucose and L-lactate at concentrations found in sheep blood. Under these conditions acetate, glucose and L-lactate contributed 95, 2 and 3%, respectively, of the C2 units used for fatty acid synthesis in adipose tissue slices from adult sheep. In contrast, acetate, glucose and L-acetate provided 50, 17 and 33%, respectively, of the C2 units for fatty acid synthesis in adipose tissue slices from foetal lambs (about 30 days prior to birth). The contribution of acetate and L-lactate carbon to fatty acid synthesis varied with their concentrations over the normal physiological range at both ages. We conclude that L-lactate is normally a minor source of carbon for fatty acid synthesis in the adult sheep but is an important source in foetal lambs.

The effects of colchicine and vincristine on the concentrations of glucose and related metabolites in goat's milk.

The effects of colchicine and vincristine on the concentration of glucose and its metabolites in milk were studied following intramammary injection of the alkaloids into one mammary gland of lactating goats. Both alkaloids decreased the rate of milk secretion from the treated gland and produced similar changes in the concentrations of various metabolites in milk. The concentrations of glucose, UDP-galactose, galactose, pyruvate and lactate increased, while those of glucose 6-phosphate and phosphoenolpyruvate decreased in milk from treated glands. The rate of milk secretion from the untreated gland increased, along with the concentrations of glucose in the milk. The changes in the concentrations of the metabolites in milk are discussed in relation to possible biochemical changes occurring in the mammary gland during the suppression of milk secretion by the alkaloids. It is suggested that, before alkaloid treatment, the rate of milk secretion was limited by intracellular glucose supply.

A selective peroxisome proliferator-activated receptor-gamma (PPARgamma) modulator blocks adipocyte differentiation but stimulates glucose uptake in 3T3-L1 adipocytes.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists such as the thiazolidinediones are insulin sensitizers used in the treatment of type 2 diabetes. These compounds induce adipogenesis in cell culture models and increase weight gain in rodents and humans. We have identified a novel PPARgamma ligand, LG100641, that does not activate PPARgamma but selectively and competitively blocks thiazolidinedione-induced PPARgamma activation and adipocyte conversion. It also antagonizes target gene activation as well as repression in agonist-treated 3T3-L1 adipocytes. This novel PPARgamma antagonist does not block adipocyte differentiation induced by a ligand for the retinoid X receptor (RXR), the heterodimeric partner for PPARgamma, or by a differentiation cocktail containing insulin, dexamethasone, and 1-methyl-3-isobutylxanthine. Surprisingly, LG100641, like the PPARgamma agonist rosiglitazone, increases glucose uptake in 3T3-L1 adipocytes. Such selective PPARgamma antagonists may help determine whether insulin sensitization by thiazolidinediones is mediated solely through PPARgamma activation, and whether there are PPARgamma-ligand-independent pathways for adipocyte differentiation. If selective PPARgamma modulators block adipogenesis in vivo, they may prevent obesity, lower insulin resistance, and delay the onset of type 2 diabetes.

The effects of the GABA agonist muscimol upon blood flow in different vascular territories of the rat cortex.

Local cerebral blood flow was measured in five regions of rat cortex immediately following intravenous administration of the gamma-aminobutyric acid (GABA) agonist muscimol. In contrast to recent observations, no increases in blood flow were found at either of the two time points analysed, and the data revealed that decreases in blood flow previously reported 30 min after muscimol treatment were in evidence as early as 30 s. These results are totally consistent with the conclusion that the overall effects of GABA agonists in the intact animal are to reduce blood flow in line with reduced metabolic demand in the neuropil. However, the heterogeneity of the reductions in cortical blood flow found here possibly suggests a biological role for vascular GABA systems in providing a mitigating influence on fluctuating tissue perfusion.

Helping cancer patients disclose their concerns.

Health professionals are reluctant to enquire actively about cancer patients' concerns and feelings. They fear that probing will damage patients psychologically and believe they have had insufficient training in the relevant interviewing skills. In considering how their interviewing skills might be improved, the key question is which interviewing behaviours promote patient disclosure and which inhibit it. To test our predictions about the utility of specific interviewing behaviours, we asked 206 health professionals, who were attending workshops on communication and counselling skills, to interview a simulated patient before and after the workshop to establish the patient's current problems. They were given 20 min to do this and the interviews were tape-recorded and transcribed to permit detailed assessment by trained raters using an utterance by utterance analysis. This permitted the form, function, content and emotional level of each utterance to be rated. Correlation coefficients were calculated between specific interviewing behaviours and patient disclosure of significant information. Significant information was defined as any information disclosed by patients about their perceptions of their illness or prognosis or any adverse physical, psychological or social sequelae of their cancer and treatment. Spearman correlation coefficients were calculated between specific interviewing behaviours and patient disclosure. The use of these behaviours by those 41 (20%) of interviewers who achieved most disclosure was compared with those 41 (20%) who obtained least disclosure. Patient disclosure of significant information was promoted by the use of open directive questions, focusing on and clarifying psychological aspects, empathic statements, summarising and making educated guesses. The use of leading questions, focusing on and clarifying physical aspects, moving into advice and reassurance mode inhibited patient disclosure. Inhibitory behaviours were used 2-3 times more frequently before training than facilitative ones. Training of health professionals involved in cancer care should, therefore, ensure they acquire these positive skills and relinquish the inhibitory behaviours.

Novel (2E,4E,6Z)-7-(2-alkoxy-3,5-dialkylbenzene)-3-methylocta-2,4,6-trienoic acid retinoid X receptor modulators are active in models of type 2 diabetes.

Previous data have shown that RXR-selective agonists (e.g., 3 and 4) are insulin sensitizers in rodent models of non-insulin-dependent diabetes mellitus (NIDDM). Unfortunately, they also produce dramatic increases in triglycerides and profound suppression of the thyroid hormone axis. Here we describe the design and synthesis of new RXR modulators that retain the insulin-sensitizing activity of RXR agonists but produce substantially reduced side effects. These molecules bind selectively and with high affinity to RXR and, unlike RXR agonists, do not activate RXR homodimers. To further evaluate the antidiabetic activity of these RXR modulators, we have designed a concise and systematic structure-activity relationship around the 2E,4E,6Z-7-aryl-3-methylocta-2,4,6-trienoic acid scaffold. Selected compounds have been evaluated using insulin-resistant rodents (db/db mice) to characterize effects on glucose homeostasis. Our studies demonstrate the effectiveness of RXR modulators in lowering plasma glucose in the db/db mouse model.

High-risk behaviors among high school students in Massachusetts who use anabolic steroids.

OBJECTIVE: To assess the association between the frequency of anabolic steroid use and the frequency of other health risk and problem behaviors among high school students in Massachusetts. METHODS: The 1993 Massachusetts Youth Risk Behavior Survey was conducted on a random sample of 3054 high school students (49% male; mean age, 16 +/- 1.2 years). The frequency of lifetime anabolic steroid use was measured on an ordinal scale from 1 to 6, representing "0" to "40 or more times." Other health risk and problem behaviors measured were sexual behaviors, suicidal behaviors, frequency of not wearing a passenger seat belt, riding a motorcycle, not wearing a helmet while riding a motorcycle, driving after drinking alcohol, riding with a driver who had been drinking alcohol, fighting, and carrying a weapon. The associations between the frequency of anabolic steroid use and other high-risk behaviors were determined using the Spearman correlation coefficient for ordinal data and the Kruskall-Wallis analysis of variance for categorical data. Representative indicators of each risk behavior significantly associated with anabolic steroid use were then analyzed using a stepwise multiple-regression analysis. RESULTS: The frequency of anabolic steroid use was associated with all of the other high-risk behaviors analyzed. Using multiple-regression analysis, driving after drinking alcohol accounted for 12.5% of the variance of the model. Carrying a gun, the number of sexual partners within the past 3 months, not using a condom during last intercourse, injury in a physical fight requiring medical attention, history of a sexually transmitted disease, not wearing a helmet on a motorcycle, not wearing a passenger seatbelt, and a suicide attempt requiring medical attention accounted for an additional 9.0% of the variance. The full model accounted for greater than 21% of the variation. CONCLUSIONS: The frequency of anabolic steroid use among adolescents is associated with other high-risk behaviors, thus supporting the hypothesis that anabolic steroid use is part of a "risk behavior syndrome" rather than an isolated behavior. This finding emphasizes the need for comprehensive high-risk behavior screening and counseling among teens who use anabolic steroids.

Metabolic responses to euglycaemic hyperinsulinaemia in lactating and non-lactating sheep in vivo.

Glucose utilization and production and changes in concentrations of plasma metabolites were studied in lactating and non-lactating sheep in response to three levels of insulin infusion whilst maintaining euglycaemia. Glucose utilization and production responded to insulin infusion similarly in both lactating and non-lactating ewes but, as circulating concentrations of insulin were lower in lactating animals, these parameters appeared more sensitive to plasma concentrations of insulin in lactating sheep. Changes in plasma concentrations of glycerol and free fatty acids during lactation indicated reduced sensitivity to insulin in adipose tissue and changes in plasma concentrations of amino acids were also less during lactation, suggesting reduced sensitivity of protein synthesis to insulin. Changes in plasma concentrations of urea and beta-hydroxybutyrate during lactation were similar to those in non-lactating animals, indicating similar insulin sensitivity of hepatic metabolism. It is concluded that during lactation ovine adipose tissue and muscle are more resistant to increased concentrations of insulin but that the sensitivity of the sheep liver is unchanged or increased. The rate of removal of insulin from the circulation was higher in lactating animals.

Effects of truncated glucagon-like peptide-1 on the responses of starved sheep to glucose.

The effects of i.v. glucagon-like peptide-1-(7-36)amide (GLP-1; 10 micrograms) on starved sheep given an i.v. glucose load (5 g) were studied. Plasma insulin concentrations rose significantly more after glucose administration in fed than in starved sheep. Giving GLP-1 to starved sheep increased the insulin response to the glucose load. The rise in plasma insulin concentrations in starved sheep given GLP-1 was similar to that observed in fed sheep. Plasma glucose concentrations returned to normal values more quickly in the starved sheep given GLP-1 than in starved sheep not given gut hormone. Plasma concentrations of free fatty acid, urea and alpha-amino nitrogen decreased more quickly following glucose administration in starved sheep given GLP-1 than in those not given GLP-1. The data suggest a role for GLP-1 in regulating plasma insulin concentrations and hence metabolism in ruminant animals. The possible role of gut hormones in ruminants is discussed.

Effects of somatostatin-28 on circulating concentrations of insulin and gut hormones in sheep.

The effects of intravenous somatostatin-28 (S28) infusion on glucose-stimulated and glucagon-like peptide-1(7-36)amide (GLP-1)-augmented insulin secretion were studied in sheep. S28 was infused via a jugular catheter for 15 min at a rate of 1.1 pmol/kg/min either alone or together with GLP-1 and/or glucose. S28 infusion did not significantly lower circulating basal insulin concentrations in fed sheep. Glucose-stimulated insulin secretion was significantly inhibited by S28 infusion, serum concentrations decreasing from about 200 to 150 pmol/l. GLP-1 significantly augmented glucose-stimulated insulin secretion, serum concentrations increasing from about 230 to 280 pmol/l. S28 completely counteracted this effect of GLP-1. S28 infusion also significantly decreased the circulating concentrations of glucose-dependent insulinotrophic polypeptide (GIP) and GLP-1 in fed sheep (from about 110 to 45 pmol/l for GIP and from about 25 to 15 pmol/l for GLP-1). The physiological implications of these observations are discussed with particular reference to the ruminant. It is concluded that S28 may have an important endocrine role in the control of insulin secretion and regulation of nutrient partitioning.