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Biomedical subjects

A Ballinger

Publications and source records attributed to A Ballinger.

At least 19 recordsLinked to original sources
PubMed2001

COX-2 inhibitors vs. NSAIDs in gastrointestinal damage and prevention.

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit production of protective gastric mucosal prostaglandins and also have a direct topical irritant effect. In some patients this results in dyspepsia and development of gastroduodenal erosions and ulceration. The risk of ulcer complications, such as bleeding, perforation and death is increased approximately 4-fold in NSAID users. Patients at high risk of ulcer complications include the elderly, those taking anticoagulants, steroids and aspirin, those with a previous history of peptic ulceration and patients with concomitant serious medical problems. The interaction of NSAIDs with Helicobacter pylori (the major cause of peptic ulceration in non-NSAID users) is controversial and some studies suggest that H. pylori infection may even protect against NSAID-induced ulceration. Selective inhibitors of the inducible cyclooxygenase-2 (COX-2) enzyme spare COX-1 in the gastric mucosa and, hence, do not inhibit production of mucosal prostaglandins. COX-2-selective inhibitors are associated with a significant reduction in gastroduodenal damage compared with traditional NSAIDs. Proton pump inhibitors (PPI) are probably the best agents for healing and prevention of NSAID-induced ulcers. Preliminary studies suggest that COX-2 selective inhibitors, like traditional NSAIDs, may prevent lower gastrointestinal cancer. Further studies are needed but they may be useful in individuals at high risk of certain types of lower gastrointestinal malignancy with increased gastrointestinal tolerability and safety.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

The role of medial hypothalamic serotonin in the suppression of feeding in a rat model of colitis.

BACKGROUND & AIMS: Experimental colitis is associated with anorexia that is attenuated by treatment with an interleukin (IL)-1 receptor antagonist. Serotonin (5-hydroxytryptamine [5-HT]) is a potent inhibitor of feeding, and its release from the hypothalamus is stimulated by IL-1. We have tested the hypotheses that anorexia associated with experimental colitis results from increased activity of hypothalamic 5-HT neurons and that the increase in activity occurs secondary to an increase in availability of tryptophan, the precursor of 5-HT. METHODS: In vivo 5-HT release and regional hypothalamic 5-HT and tryptophan concentrations were measured in rats with 2,4,6,-trinitrobenzene sulfonic acid (TNBS)-induced colitis, healthy controls, and animals pair-fed to match the food intake of the colitic group. Food intake in the colitic group was assessed after depletion of brain 5-HT by p-chlorophenylalanine (PCPA). RESULTS: In the colitic group, release of 5-HT from the hypothalamic paraventricular nucleus (PVN) was 3-fold (P = 0.01) and 14-fold (P < 0.001) higher than in control and pair-fed groups, respectively. Concentrations of tryptophan were similar in each group in all hypothalamic regions. Food intake was significantly increased in the colitic group after PCPA treatment but was not restored to control values. CONCLUSIONS: In animals with TNBS-induced colitis, 5-HT release from the PVN is increased. The increase in food intake after depletion of brain 5-HT suggests that hypothalamic 5-HT contributes to anorexia but is not the only mediator. Increased 5-HT release in the colitic group was not driven by increased precursor availability.

Amino Acids↗
PubMed2000

Orlistat in the treatment of obesity.

Orlistat (Xenical, Hoffmann-La Roche) is a powerful inhibitor of gastrointestinal lipase and as such, reduces fat absorption. Unlike other weight-reducing drugs it is minimally absorbed and has no effects in the CNS. Orlistat is indicated for patients with a body mass index (BMI) of at least 30 kg/m2 or 28 kg/m2 in the presence of obesity-associated complications, such as hypertension, diabetes mellitus, hyperlipidaemia and obstructive sleep apnoea. In clinical trials, orlistat (120 mg t.i.d.) in combination with life-style modification and a hypocaloric diet (30% of energy from fat) induced significantly more weight loss and improved health complications of obesity (diabetes, hypertension, hyperlipidaemia) compared to patients treated with diet alone. Side effects related to fat malabsorption, occurred in more than 20% of subjects during the first year of treatment and included oily faecal spotting, abdominal pain, flatus with discharge and fatty/oily stool. Side effects from orlistat diminished in the second year of treatment. Plasma concentrations of fat soluble vitamins decreased in orlistat-treated patients but did not usually fall below the normal range. No studies have evaluated the efficacy of orlistat or side effect profile beyond two years.

Anti-Obesity Agents↗
PubMed1999

Gastric leptin.

Explore the source record for details and available documents.

Animals↗
PubMed1998

Plasma leptin in chronic inflammatory bowel disease and HIV: implications for the pathogenesis of anorexia and weight loss.

1. Leptin inhibits food intake and is an important regulator of long-term energy balance. In rodents, plasma concentrations of leptin are increased by administration of interleukin-1 and tumour necrosis factor. Hyperleptinaemia may mediate the anorexia and weight loss which is observed in chronic infections and inflammatory conditions. 2. Plasma leptin and soluble tumour necrosis factor receptor (sTNF-r55) concentrations were measured in patients with inflammatory bowel disease and acquired immunodeficiency syndrome (AIDS), and healthy controls. 3. The patients with AIDS were severely wasted [% body fat 12 (9-16); median (interquartile range)] compared with those with inflammatory bowel disease [25.1 (19-31.5)] and control subjects [29.4 (23.6-37.8)]. Leptin concentrations were highly correlated with percentage body fat in controls (r = 0.74, P < 0.001) and patients with IBD (r = 0.73, P < 0.001) but not in the patients with AIDS (r = -0.024). Leptin concentrations were similar in the inflammatory bowel disease [4.8 (2.6-10.1) ng/ml] and control groups [8.0 (3.1-14.1) ng/ml] but were significantly lower (P < 0.05) in patients with AIDS [1.8 (1.5-2.3) ng/ml] after 23 patients were matched for sex and percentage body fat in patients with inflammatory bowel disease [2.4 (1.8-4.1) ng/ml]. Plasma concentrations of sTNF-r55 were higher in both the patients with inflammatory bowel disease [0.19 (0.16-0.23) ng/ml] and those with AIDS [4.8 (2.8-7.3) ng/ml] compared with controls [0.14 (0.09-0.16) ng/ml] but were not correlated with either percentage body fat or plasma leptin concentrations. 4. Hyperleptinaemia does not appear to mediate the anorexia and weight loss associated with inflammatory bowel disease and AIDS. In patients with AIDS with extreme wasting there was no relationship between body fat and leptin and this may be related to the rapid weight loss which occurs in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1998

A prospective study of K-ras mutations in the plasma of pancreatic cancer patients.

K-ras mutations are frequently found in primary pancreatic adenocarcinomas. In this prospective study, we looked for K-ras mutations in the plasma of patients with pancreatic cancer. We isolated plasma DNA from 21 pancreatic cancer patients using a simple and rapid extraction technique and detected K-ras alterations with a PCR assay and subsequent product sequencing. Patients were followed up to determine their clinical outcome. We found K-ras mutations in the plasma of 17 patients (81%). In cases in which both plasma and pancreatic tissue were available, DNA mutations were similar in corresponding plasma and tissue samples. Plasma DNA alterations were found 5-14 months before clinical diagnosis in four patients. Mutant DNA was not found in the plasma of two patients with chronic pancreatitis or in five healthy controls. Our results indicate that K-ras mutations are often found in DNA isolated from the plasma of pancreatic cancer patients and that a noninvasive plasma-based assay may provide qualitative diagnostic information to clinicians in the future. Larger studies are required to further assess the relevance of our findings to clinical practice.

Adult↗
PubMed1997

Gastrin effects on growth and exocrine secretion in the neonatal rat pancreas.

In adult rats, cholecystokinin (CCK) binds to pancreatic CCK-A receptors and stimulates exocrine secretion and pancreatic growth. In newborn rats there is very little mature intestinal CCK and few pancreatic CCK-A receptors. However, there is an abundant source of the related peptide gastrin, and in addition, there are pancreatic CCK-B/gastrin receptors. In this study, we have explored the hypothesis that gastrin may "deputise" for CCK in the neonate and cause pancreatic exocrine secretion, growth, and maturation. Newborn rats were injected intraperitoneally with the gastrin antagonist, C1-988, or placebo for 5 days and sacrificed on day 6. Body weight (CI-988, 8.25 +/- 0.48 g; placebo, 10.17 +/- 0.93 g) and pancreatic weight (19.41 +/- 1.5 vs. 21.58 +/- 1.72 mg) were the same. Protein (1,202 +/- 78 vs. 1,254 +/- 56 micrograms), amylase (22.3 +/- 0.9 vs. 19.2 +/- 1.00 U), RNA (117 +/- 7 vs. 126 +/- 5 micrograms), and DNA (95 +/- 8 vs. 100 +/- 7 micrograms) contents of the pancreas were similar in the two groups. The weight of the stomach was reduced (p = 0.04) in the treated group (50.8 +/- 2.5 mg) compared to the placebo group (59.8 +/- 3.7 mg). In both neonates and adults, CCK-8 was approximately 1,000 times more potent than gastrin-17 in stimulating amylase release from isolated pancreatic acini. This suggests that enzyme release is probably mediated by the same receptors in both adults and neonates, and in adults previous work has shown this to be the CCK-A receptor. In conclusion, these data show that gastrin has very weak effects on neonatal pancreatic exocrine secretion, and furthermore, gastrin is not essential for growth and maturation of the neonatal pancreas. The role of gastrin and CCK-B/gastrin receptors in the neonatal pancreas remains speculative.

Amylases↗
PubMed1997

Highlights of the year in gastroenterology.

The past 12 months have been a period of steady progress in the field of gastroenterology. Helicobacter pylori continues to dominate many areas of clinical research and the indications for eradication are increasing. A potent, topically-acting corticosteroid for Crohn's disease, and new hope and potential treatments for IBS sufferers are other developments.

Administration, Topical↗
PubMed1996

A double-blind randomized trial of low-dose versus high-dose topical anaesthesia in unsedated upper gastrointestinal endoscopy.

BACKGROUND: Upper gastrointestinal endoscopy is frequently performed on unsedated subjects. Pharyngeal anaesthesia is thought to improve patient tolerance to the procedure but the optimum dose of anaesthesia is not known. The aim of this study was to assess the benefits of low-dose vs. high-dose topical anaesthesia in unsedated gastroscopy. METHODS: One hundred and fourteen subjects attending for diagnostic gastroscopy were studied. Patients were randomized to receive either 30 mg or 100 mg of topical pharyngeal lidocaine spray prior to endoscopy in a double-blind fashion. Subjects completed a questionnaire before and after endoscopy. RESULTS: A similar proportion of patients in each group required intravenous sedation because of discomfort or anxiety during the procedure (P = 0.48). The high-dose group experienced less discomfort during endoscope insertion (P = 0.002) and throughout the examination (P = 0.01). Overall satisfaction was almost identical in the two groups (P = 0.85) and a similar percentage of the high-dose and low-dose groups stated that they would request sedation prior to future endoscopy (37 vs. 44%; P = 0.48). Further analysis showed that apprehensive patients and younger patients reported relatively high levels of discomfort, and that female subjects were more likely to express a preference for sedation at any future gastroscopy. CONCLUSION: High-dose pharyngeal anaesthesia reduces patient discomfort during unsedated upper gastrointestinal endoscopy. However, patient tolerance is also influenced by clinical features, which might be useful in deciding which patients are suitable for this procedure.

Administration, Topical↗
PubMed1995

Cholecystokinin is a satiety hormone in humans at physiological post-prandial plasma concentrations.

1. Intravenous infusions of the brain/gut hormone, cholecystokinin, have been shown to reduce food intake in a subsequent test meal. However, in previous studies the doses administered were large and likely to have produced plasma concentrations far in excess of the normal post-prandial range. 2. In this study cholecystokinin-8 was infused intravenously to six healthy subjects in doses that reproduced physiological post-prandial concentrations. Plasma concentrations of cholecystokinin were measured using a novel sensitive and specific radioimmunoassay. The effect of cholecystokinin-8 infusion on subsequent food intake in a standard test meal was compared with the effect of saline infusion in the same subjects. 3. Food intake (mean +/- SEM) was significantly less during cholecystokinin (5092 +/- 665 kJ) than during saline infusion (6418 +/- 723 kJ, P = 0.03). During cholecystokinin infusion, plasma concentrations increased from 0.45 +/- 0.06 pmol/l to 7.28 +/- 2.43 pmol/l immediately before the meal. With saline infusion there was no premeal increase in plasma cholecystokinin concentration. 4. This paper describes a novel radioimmunoassay for measurement of plasma concentrations of cholecystokinin. Using this assay we have demonstrated that cholecystokinin is important in control of satiety in humans.

Adult↗
PubMed1993

Promotion of gallbladder emptying by intravenous aminoacids.

Patients receiving total intravenous nutrition have inert gallbladders; gallbladder sludge and gallstones often develop, but are preventable if gallbladder emptying can be improved. We measured the effect of giving rapid intravenous infusions of aminoacid solutions in eight normal subjects. Four regimens were tested (250 mL over 30 min, 250 mL over 10 min, 125 mL over 5 min, and 50 mL over 5 min). Gallbladder emptying, as measured by ultrasound and cholecystokinin release, depended on both the amount and the rate of aminoacid infusion. Rapid infusion of 125 mL of an aminoacid mixture (Synthamin 14 without electrolytes) over 5 min (2.1 g per min) produced a 64% reduction in gallbladder volume within 30 min, whereas a 50 mL infusion over 5 min produced only a 22% reduction. Intermittent rapid infusion of small amounts of aminoacids may prevent gallstones in patients receiving intravenous nutrition.

Adult↗
PubMed1992

Ulcerative colitis complicated by Wenckebach atrioventricular block.

Extracolonic manifestations of inflammatory bowel disease are common and diverse. Cardiac complications, however, are rare and of these pericarditis is the most frequently described association. A 57 year old man with a 20 year history of ulcerative colitis presented with a four day history of retrosternal chest pain and exertional dyspnoea. Electrocardiogram showed Wenckebach atrioventricular block. Three days later he developed bloody diarrhoea and sigmoidoscopy showed active proctocolitis. He was treated with oral prednisolone after which the chest pain and diarrhoea settled within 48 hours. At outpatient review two weeks later he was completely well and the electrocardiogram had returned to normal.

Colitis, Ulcerative↗