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Glucagon metabolism under basal (endogenous) conditions and during intravenous glucagon infusion was studied in anesthetized pigs by use of midregion (M), COOH-terminal (C), and NH2-terminal (N)-RIAs. Arteriovenous concentration differences revealed a negative extraction of endogenous glucagon immunoreactivity across the portal bed (-35.4 +/- 11.0, -40.3 +/- 9.6, -35.6 +/- 16.9%, M-, C-, N-RIA, respectively), reflecting net secretion of pancreatic glucagon and intestinal glicentin and oxyntomodulin, but under exogenous conditions, a net extraction occurred (11.6 +/- 3.6 and 18.6 +/- 5.7%, C- and N-RIA, respectively). Hindlimb extraction of endogenous (17.4 +/- 3.7%, C-RIA) and exogenous (29.1 +/- 4.8 and 19.8 +/- 5.1%, C- and M-RIA) glucagon was detected, indicating M and C cleavage of the molecule. Renal extraction of glucagon was detected by all assays under endogenous (19.4 +/- 6.7, 33.9 +/- 7.1, 29.5 +/- 6.7%, M-, C-, N-RIA) and exogenous conditions (46.9 +/- 4.8, 46.4 +/- 6.0, 47.0 +/- 7.7%; M-, C-, N-RIA), indicating substantial elimination of the peptide. Hepatic glucagon extraction was undetectable under basal conditions and detected only by M-RIA (10.0 +/- 3.8%) during glucagon infusion, indicating limited midregional cleavage of the molecule. The plasma half-life determined by C- and N-RIAs (2.7 +/- 0.2 and 2.3 +/- 0.2 min) were similar, but both were shorter than when determined by M-RIA (3.2 +/- 0.2 min, P < 0.02). Metabolic clearance rates were similar regardless of assay (14.4 +/- 1.1, 13.6 +/- 1.7, 17.0 +/- 1.7 ml x kg-1 x min-1, M-, C-, N-RIA). Porcine plasma degraded glucagon, but this was not significantly affected by the dipeptidyl peptidase IV (DPP IV) inhibitor valine-pyrrolidide, and in anesthetized pigs, glucagon's metabolic stability was unchanged by DPP IV inhibition. We conclude that tissue-specific metabolism of glucagon occurs, with the kidney being the main site of removal and the liver playing little, if any, role. Furthermore, valine-pyrrolidide has no effect on glucagon stability, suggesting that DPP IV is unimportant in glucagon metabolism in vivo, in contrast to its significant role in the metabolism of the other proglucagon-derived peptides and glucose-dependent insulinotropic polypeptide.

Objective: To study the role of cyclooxygenase (COX) inhibition on the development of advanced atherosclerosis in apolipoprotein E-deficient (apoE(-/-)) mice., Design: Sixty apoE(-/-) mice were divided into three groups: a control group, a group fed standard mouse chow supplemented with 0.0067% (wt/wt) MF Tricyclic (selective COX-2 inhibitor), and a group fed the diet supplemented with 0.0134% (wt/wt) sulindac (non-selective COX inhibitor). Four months later, the mice were killed and the atherosclerotic plaque area in the aortic root was measured., Results: Mean body weights did not differ at any time. The MF Tricyclic and sulindac groups had drug plasma levels of 1.31 +/- 0.11 and 0.84 +/- 0.23 micro g/ml, respectively. Plasma total cholesterol and triglyceride values were similar in all three groups. A small difference in plasma levels of high-density lipoprotein cholesterol was found between the groups (p = 0.03). Advanced atherosclerotic plaques were present in mice from all three groups, but there was no difference in mean plaque size between the groups (p = 0.9)., Conclusion: Neither selective COX-2 nor non-selective COX inhibition influenced the development of advanced atherosclerosis in apoE(-/-) mice.

Collagenous colitis and lymphocytic colitis are newly described colitides that are only diagnosable microscopically; therefore, both are known under the umbrella term 'microscopic colitis'. This is a short review of the clinical findings, and epidemiological and basic observations of these relatively little described colitides belonging to the group of inflammatory bowel diseases.

Background: Interest in fructooligosaccharides as a health-promoting food component is increasing. Fructooligosaccharides are mainly indigestible and large amounts in the colon may provoke gastrointestinal symptoms., Objective: The symptoms of irritable bowel syndrome (IBS) may be provoked by large quantities of carbohydrates in the colon. The objective of this study was to determine whether regular consumption of fructooligosaccharides worsens gastrointestinal symptoms in patients with IBS., Design: A multicenter, prospective, randomized, double-blind, placebo-controlled parallel group comparison was conducted at 24 sites. The study consisted of a 2-wk, single-blind run-in phase and a 12-wk, double-blind comparative phase. Subjects were randomly assigned to receive 20 g fructooligosaccharides powder/d (n = 52) or a placebo (n = 46). Efficacy was based on the patients' overall response to treatment at completion of the study and on the severity and duration of individual symptoms (abdominal distension, abdominal rumbling, abnormal flatulence, and abdominal pain)., Results: Data from 96 patients (16 men and 80 women) were analyzed. After 4-6 wk of treatment, IBS symptoms improved more in the placebo group than in the fructooligosaccharide group. After completion of the study, there were no significant differences between the 2 groups: symptoms improved in 58% of the fructooligosaccharide group and in 65% of the placebo group and symptoms worsened in 8% of the fructooligosaccharide group and in 13% of the placebo group., Conclusion: Although symptoms worsened in patients with IBS at the onset of treatment with 20 g fructooligosaccharides/d, continuous treatment for 12 wk resulted in no worsening of symptoms.

Low-radiation-dose computed tomography (low-dose CT) is a new, promising technology presently used in screening for lung cancer in some medical centres in the USA and Japan. The three population-based studies of the efficacy of screening with low-dose CT published to date all show that more than 85% of the lung cancers detected by low-dose CT are in stage I, offering improved possibility for curative treatment. The number of false positive scans, was up to 20%. The radiation dose per low-dose CT scan was approximately the dose of a mammography (1 mSv). In two studies, low-dose CT failed to detect some centrally located tumours. None of the studies are capable of evaluating changes in lung cancer mortality in a screened population compared to those of a control population. There is, therefore, a need for further assessments of positive as well as negative effects of population-based screening with low-dose CT.

Objective: To study processing and fermentability in the human gastro-intestinal tract of a newly isolated, enzymatically modified, soluble, and highly concentrated (> 80% dietary fibres) solubilised potato fibre (SPP)., Setting: Gastroenterological laboratory. DESIGN, SUBJECTS AND INTERVENTIONS: Seven healthy volunteers ingested in random order on seven different days: 20 g SPP; bread made of 180 g wheat flour served with 20 g raw SPP; bread baked of 180 g wheat flour and 20 g SPP; bread made from 180 g what flour; 20 g lactulose; 20 g oat bran; and 20 g wheat bran. The hydrogen breath test was used to evaluate oro-coecal transit time (OCTT) and fermentation., Results: Fermentation of SPP yielded a measurable increase in end-expiratory H2. The total incremental increase in end expiratory H2 due to SPP was unaffected of whether SPP was served alone, as the raw flour served with bread, or baked into bread. The OCTT for raw SPP was significantly delayed compared to lactulose (P = 0.01). The OCTT for SPP baked into bread was significantly delayed compared to raw SPP (P = 0.01), indicating that SPP may be used as a marker of oro-coecal transit time for as well the fluid phase as the solid phase of a meal., Conclusions: SPP is a fermentable, highly concentrated soluble fibre source. Baking SPP did not interfere with the fermentable properties. Thus, SPP may be interesting as a fibre-supplement in fibre-poor diets. The change in oro-coecal transit time for SPP, depending on the composition of the total meal, makes SPP interesting as a marker in studies of gastrointestinal transit.

The production of nitric oxide (NO) is increased in active ulcerative colitis and in Crohn's disease. We have studied NO production in collagenous colitis (CC) and lymphocytic colitis (LC), both of which are inflammatory bowel disorders of unknown aetiology. NO levels were measured directly in gas sampled from the colon during colonoscopy. Plasma levels of NO metabolites (nitrate/nitrite) were also measured. Luminal NO levels were more than 100 times higher in patients with CC compared with controls. In addition, plasma levels of nitrate/nitrite were increased in the patients as compared with controls. Measurements of NO directly in the colon or its oxidation products in plasma may be a helpful tool in further understanding the role of NO in the pathophysiology of CC and LC. Moreover, it is tempting to speculate that these measurements could be clinically useful in the diagnosis and therapy monitoring of these two inflammatory bowel diseases.

Objective: Concentrations of plasma neutral amino acids, i.e. threonine, serine, asparagine, glycine, alanine, citrulline, alpha-aminobutyric acid, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, and tryptophan, and serum cholesterol, were determined at the follicular (Day 4), mid-cycle (Day 16) and luteal (Day 25) phases of the menstrual cycle in 15 users of the new generation of combined oral contraceptives (OC), 11 on multiphase combined OC, and 17 controls., Results: The controls showed a decrease in the sum of amino acids to 95% at mid-cycle and 90% in the luteal phase relative to the follicular phase, and a significant decrease in the tyrosine level at the luteal relative to the follicular phase. Since there was no significant difference between the two OC subgroups in the levels of the specified variables at either of the phases, the two groups were considered together. The sum of amino acids in the OC group decreased to 89% at mid-cycle and 91% at the luteal phase relative to the follicular phase, indicating less metabolic effect than reported for older OC formulations. Compared to the controls, the OC group showed significant increased threonine level at the luteal phase, decreased glycine levels at mid-cycle and the luteal phases, decreased citrulline level at mid-cycle, and markedly decreased tyrosine levels at the mid-cycle and luteal phases. Neither total nor high density lipoprotein (HDL) cholesterol differed significantly between the control and OC groups., Conclusion: The results suggest that the metabolic effects of the new generation combined OC on neutral amino acids and cholesterol are only modest to slight, except for the effect on tyrosine, the brain noradrenaline precursor, which may cause disturbances of various noradrenaline-mediated central functions in susceptible subjects.

Solid organ transplant provides lifesaving therapy for infants and children with otherwise terminal diseases, but it is severely limited by donor organ supply. Medical examiners perform a pivotal role in the organ procurement process by determining whether a "heartbeating cadaver" on life support is a medicolegally suitable donor. This descriptive questionnaire study assesses medical examiner practice and behavior regarding organ procurement from child abuse/homicide victims. Obtaining forensic evidence for judicial purposes and releasing organs to children awaiting transplantation are not necessarily conflicting values. Greater than 60% of medical examiners sampled would agree to release organs from abuse/homicide victims in the scenarios presented here if provided with requested information. Further confronting the origins of variable medical examiner practice in this area might result in the availability of additional solid organs for pediatric transplantation.

Objective: To study fermentability of different samples of resistant starch (RS), compared to one another and to lactulose, and to study the effect on gastric emptying of addition of RS to test meal. Finally to study if adaptation to RS results in a measurable change in fermentation pattern, (H2/CH4 production). Sources of RS: Raw potato starch (RPS), 58% RS; corn flakes (CF), 5% RS; hylon VII high amylomaize starch, extrusion cooked and cooled (HAS) 30% RS; highly retrograded hylon VII high amylomaize starch (HRA) 89% RS., Design: (1) Fermentation: seven healthy volunteers ingested in randomized order 50 g RPS, 100 g CF, 75 g HAS, 25 g HRA. End-expiratory H2/CH4 was measured every 30 min for 12 to 22 hours post-ingestion as a measure of fermentation. A dose-response study of RPS, 5, 10, 25, 50, 75 and 100 g was performed. (2) Adaptation: In five 3-week periods seven volunteers added daily to their usual diet 50 g of either RPS, HAS, oat bran, wheat bran or common maize starch. The polysaccharides were administered in randomized order. The test periods were separated by 1 week's wash out. Basic end-expiratory H2/CH4 was measured once a week prior to and during the test periods. (3) Gastric emptying: The rate of increase in blood glucose was measured after test meals consisting of 50 and 100 g of RPS, 50 g HAS and 50 g glucose dissolved in a gel, alone, and mixed with 25 g of RPS. As controls we chose wheat bran and oat bran., Results: (1) We found that RPS is fermentable, although the cumulated excessive H2 production after 50 g RPS corresponding to 29 g RS was clearly less than after 10 g lactulose. The time from ingestion of RPS to a sustained increase in end-expiratory H2 (apparent transit time; 5-11 h) was longer than lactulose (1-4 h), indicating either a slow passage through the small intestine or a slow fermentation rate. 100 g of corn flakes (4.6 g RS) resulted in a measurable increase in H2 production, equivalent to 10-20 g RPS, whereas neither of the two samples of hylon VII high amylomaize resulted in any significant increase in H2 production. The dose-response study with RPS showed that even 5 g of RPS resulted in a measurable increase in end-expiratory H2, and increasing doses from 5 g to 100 g resulted in a seemingly exponential increase in H2 production. (2) 3 weeks' daily administration of HAS resulted in a slightly elevated increase in basic end-expiratory H2, although the increase did not reach statistical significance. RPS resulted in a sustained increase in basic end-expiratory H2. Both RS samples increased measurable end-expiratory CH4 in volunteers with measurable CH4 production after a lactulose load, but 3 weeks' daily challenge with these slowly fermentable substrates did not increase measurable CH4 in volunteers, who prior to the study only produced CH4 intermittently. (3) The rate of increase in blood sugar was unaffected by addition of RS or non-starch-polysaccharides to the test meal, indicating that addition of the polysaccharides does not affect gastric emptying., Conclusions: A fraction of RPS is resistant to digestion in the small intestine, and it is fermentable by the colonic microbial flora. RS from CF, HAS and RPS give very different H2 responses, either due to differences in digestion patterns or fermentation patterns. Short-term adaptation (3 weeks) to HAS or RPS does not change the H2/CH4 response. RS does not affect gastric emptying of a test meal consisting of glucose dissolved in a gel.

Placebo controlled trials of methotrexate, auranofin, penicillamine, azathioprine, sulphasalazine, gold sodium thiomalate and chloroquines were subjected to meta-analysis. The difference between drugs and placebo in the erythrocyte sedimentation rate was 8.8 mm/hr [95% confidence interval (CI), 6.4-11.3]. In multiple linear regression analyses, with the physician's global evaluation and relative change in joint tenderness count as outcome variables, a substantial sample size bias was demonstrated. The effect decreased with increasing sample size. The risk of dropping out from any cause was larger on drug than on placebo (odds ratio, 1.17; CI, 0.99-1.38). No evidence of a worthwhile effect on radiological changes was found. Of the 3439 patients, 4 went into complete remission on drug. We conclude that the benefit of second-line drugs is uncertain.

Using a newly developed radioimmunoassay for porcine gastrin-releasing peptide in plasma, we studied the pharmacokinetics of this peptide after infusing it into pigs at two dose levels. The disappearance of the peptide from plasma was characterized by two components, a fast one (t 1/2 1.4 min) and a slow one (t 1/2 6.6 min). With the same assay the release of gastrin releasing-peptide from the stomachs of 8 pigs that had been catheterized for selective sampling of fundic and antral blood was studied during vagal and splanchnic stimulation with or without acute adrenalectomy at neutral, acidic, and alkaline intragastric pH. Electrical stimulation of the vagal nerves resulted in a marked increase in both antral and fundic gastrin-releasing peptide release, whereas splanchnic stimulation was without effect. The effects of nerve stimulation were neither influenced by intragastric pH nor by adrenalectomy. Because of its presence in nerves in all layers of the gastric wall, its potent effect on gastrin release, and its release after vagal stimulation, gastrin-releasing peptide is likely to play a role in the vagal control of gastrin release, gastric motility, and acid secretion.

The influence of the autonomic nervous system on the secretion of somatostatin from the antral and the fundic parts of the stomach and from the pancreas of the pig was investigated in experiments involving electrical stimulation of the vagal nerves and the splanchnic nerves in (1) intact, anesthetized pigs and (2) isolated perfused preparations of (a) antrum with intact vagal supply, (b) pancreas with intact vagal supply, (c) pancrease with intact sympathetic supply. The results clearly demonstrated that parasympathetic activity inhibits D-cell function in all gastro-pancreatic tissues; antral gastrin secretion was inversely correlated to somatostatin secretion and it is suggest that antral D-cell secretion participates in the control of gastrin secretion; the inhibitory effect of Gastric Inhibitory Polypeptide (GIP) as well as intraluminal HCl on gastrin secretion may be exerted via the stimulatory effect of both on somatostatin secretion. The sympathetic innervation of the pancreas is also clearly inhibitory to the pancreatic somatostatin secretion, whereas sympathetic nervous activity influences little the gastric somatostatin release.