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Biomedical subjects

J Hayllar

Publications and source records attributed to J Hayllar.

17 recordsLinked to original sources
PubMed2002

A three year prospective audit of 212 presentations to the emergency department after electrical injury with a management protocol.

Significant numbers of presentations to the emergency department were found to relate to low voltage electrical injury, for which there was no widely accepted management protocol. It was decided to examine the outcome of patients after low voltage electrical injury with particular reference to electrocardiogram (ECG) changes and to evaluate a protocol for managing these injuries in order to optimise the management of patients after electrical injury. A prospective observational study was done over three years of 212 consecutive presentations to the emergency department of Mount Isa Base Hospital with a four year follow up after implementation of the revised protocol. In 4% of patients, early transient conduction abnormalities were seen after low voltage electrical injury. Admissions for cardiac monitoring were reduced dramatically with no resultant ill effects. Asymptomatic patients with a normal ECG on presentation do not need ECG monitoring after low voltage electrical injury. Patients with significant symptoms or ECG changes should be admitted for monitoring and observation. In view of the high proportion of workplace related injuries occupational health measures such as "triple gloving" should be mandatory for high risk groups.

Accidents, Occupational↗
PubMed1998

Intestinal permeability and inflammation in patients on NSAIDs.

BACKGROUND: The frequency with which non-steroidal anti-inflammatory drugs (NSAIDs) increase small intestinal permeability and cause inflammation is uncertain. AIMS: To examine small intestinal permeability and inflammation in a large number of patients on long term NSAIDs. METHODS: Sixty eight patients receiving six different NSAIDs for over six months underwent combined absorption-permeability tests at three different test dose osmolarities (iso-, hypo-, and hyperosmolar). Two hundred and eighty six patients on 12 different NSAIDs underwent indium-111 white cell faecal excretion studies to assess the prevalence and severity of intestinal inflammation. RESULTS: The iso- and hyperosmolar tests showed significant malabsorption of 3-0-methyl-D-glucose, D-xylose, and L-rhamnose. Intestinal permeability changes were significantly more pronounced and frequent with the hypo- and hyperosmolar as opposed to the iso-osmolar test. Sequential studies showed that four and nine patients (of 13) developed inflammation after three and six months treatment with NSAIDs, respectively. There was no significant difference (p>0.1) in the prevalence (54-72%) or severity of intestinal inflammation in the 286 patients taking the various NSAIDs apart from those on aspirin and nabumetone, these having no evidence of intestinal inflammation. There was no significant correlation between the inflammatory changes and age, sex, dose of NSAID, length of disease, or NSAID ingestion. CONCLUSIONS: Intestinal permeability test dose composition is an important factor when assessing the effects of NSAIDs on intestinal integrity. All the conventional NSAIDs studied were equally associated with small intestinal inflammation apart from aspirin and nabumetone which seem to spare the small bowel.

Adult↗
PubMed1997

Mitochondrial damage: a possible mechanism of the "topical" phase of NSAID induced injury to the rat intestine.

BACKGROUND: The "topical" effect of non-steroidal anti-inflammatory drugs (NSAIDs) seems to be an important cause of NSAID induced gastrointestinal damage. AIM: To examine the possible mechanism of the "topical" phase of damage in the small intestine. METHODS: Electron microscopy and subcellular organelle marker enzyme studies were done in rat small intestine after oral administration of indomethacin (doses varied between 5 and 30 mg/kg). The effect of conventional and non-acidic NSAIDs on rat liver mitochondrial respiration was measured in vitro in a Clarke-type oxygen electrode. RESULTS: The subcellular organelle marker enzymes showed mitochondrial and brush border involvement within an hour of indomethacin administration. Electron microscopy showed dose dependent mitochondrial changes following indomethacin administration consistent with uncoupling of oxidative phosphorylation (or inhibition of electron transport) which were indistinguishable from those seen with the uncoupler dinitrophenol. Parenteral indomethacin caused similar changes, but not in rats with ligated bile ducts. A range of NSAIDs, but not paracetamol or non-acidic NSAIDs which have a favourable gastrointestinal tolerability profile, uncoupled oxidative phosphorylation in vitro at micromolar concentrations and inhibited respiration at higher concentrations. In vivo studies with nabumetone and aspirin further suggested that uncoupling or inhibition of electron transport underlies the "topical" phase of NSAID induced damage. CONCLUSION: Collectively, these studies suggest that NSAID induced changes in mitochondrial energy production may be an important component of the "topical" phase of damage induction.

Acetaminophen↗
PubMed1997

A randomized, double-blind, crossover comparative endoscopy study on the gastroduodenal tolerability of a highly specific cyclooxygenase-2 inhibitor, flosulide, and naproxen.

BACKGROUND: Inhibition of constitutively expressed cyclooxygenase (Cox-1) is thought to play an important role in the gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs (NSAID), while their therapeutic action may be due to inhibition of the enzyme Cox-2, which is specifically expressed at sites of inflammation. NSAIDs with high affinity and specifity for Cox-2 hold the promise of maintaining efficacy without the gastrointestinal side effects of conventional NSAIDs. METHODS: We assessed the gastrointestinal tolerability of flosulide (20 mg twice a day), a highly selective Cox-2 inhibitor with that of naproxen (500 mg twice a day), which has equal affinity for Cox-1 and -2 in 19 patients with osteoarthrosis in a randomized, double blind, crossover endoscopy study. Subjects were treated for 2 weeks with a 2-week washout period. Gastroduodenal damage was primarily assessed as by Lanza (grades 0-4). RESULTS: No stomach damage was seen in 13 (68%) patients after flosulide and in 5 (37%) after naproxen (P < 0.001). Lanza scores were significantly lower after flosulide (0.58) than after naproxen (1.47) (P < 0.001; odds ratio, 84.4; 95% confidence interval, 1.45-4908). Flosulide was significantly better tolerated (P < 0.005) than naproxen. CONCLUSION: These results endorse the idea that highly selective Cox-2 inhibitors may be associated with lesser gastrointestinal side effects than conventional NSAIDs.

Adult↗
PubMed1996

Early pathogenic events in NSAID-induced gastrointestinal damage.

A number of studies show that the idea that inhibition of cyclooxygenase is the sole mechanism of NSAID-induced gastrointestinal damage is no longer tenable. We re-examined various aspects of the mechanism of small intestinal damage due to NSAIDs in rat. Subcellular organelle marker enzyme studies show selective alterations in mitochondrial and brush border marker enzymes. Electron microscopy shows changes compatible with uncoupling of mitochondrial oxidative phosphorylation. In vitro, all common acidic-NSAIDs (n = 15) were found to uncouple oxidative phosphorylation at concentrations (microM) easily achievable within intestinal epithelium. Experiments in bile duct ligated animals show that intact indomethacin within the gastrointestinal lumen is required for uncoupling. Relative importance and pathophysiological consequences of uncoupling and inhibition of cyclooxygenase were assessed following administration of R and S flurbiprofen: the former selectively uncouples whilst the latter is also an effective cyclooxygenase inhibitor. R flurbiprofen uncoupled in vitro and in vivo, increased intestinal permeability and caused mild intestinal inflammation, but had not significant effect on prostanoid levels and produced no ulcers. S flurbiprofen uncoupled and increased intestinal permeability equally but was associated with significant decreases in intestinal prostanoid levels, more inflammation and numerous ulcers. Collectively these studies suggest that uncoupling may underlie the "topical" phase of NSAID damage which leads to increased intestinal permeability and inflammation, but concomitant inhibition of cyclooxygenase is essential to drive the inflammation to ulcers.

Animals↗
PubMed1996

Gastroduodenal tolerability of highly specific cyclo-oxygenase-2 inhibitor.

Inhibition of constitutively expressed cyclo-oxygenase (COX-1) by NSAIDs is thought to play an important role is the gastrointestinal toxicity of NSAIDs. To minimise the intestinal toxicity of NSAIDS, highly selective COX-2 (induced at inflammatory sites) inhibitors have been developed. One such is flosulide. We assessed the gastroduodenal tolerability of flosulide (20 mg twice a day) in man and compared it with that of naproxen (500 mg twice a day) in a randomised, double blind crossover fashion in 19 patients with osteoarthrosis. Treatment period was 2 weeks with a 2-week washout period with endoscopy before and after each treatment. Gastroduodenal damage was assessed as by Lanza (Grades 0-4) and by the Gastroscopic Rating Scale (Grades 0-9). Flosulide was significantly better tolerated (p < 0.005, analyses of deviance) than naproxen. No stomach damage was seen in 13 (68%) patients following flosulide and 5 (37%) following naproxen (p < 0.001). Lanza scores following flosulide (0.58) were significantly better than that of naproxen (1.47) (p < 0.001). The duodenal damage was mild with both treatments. The selective COX-2 inhibitor, flosulide, is significantly better tolerated and causes less gastric mucosal damage than naproxen when given for two weeks.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1994

Nonsteroidal antiinflammatory drug-induced small intestinal inflammation and blood loss. Effects of sulfasalazine and other disease-modifying antirheumatic drugs.

OBJECTIVE: To identify the source of intestinal blood loss in rheumatoid arthritis patients being treated with nonsteroidal antiinflammatory drugs (NSAIDs) and assess the response to sulfasalazine and other disease-modifying antirheumatic drugs (DMARDs). METHODS: Intestinal inflammation, blood loss, and gastroduodenal damage, and the response to treatment with DMARDs, were assessed in 46 patients taking NSAIDs. RESULTS: Intestinal inflammation and blood loss correlated significantly with one another (r = 0.43, P < 0.003), but not with the macroscopic or microscopic appearance of the gastroduodenal mucosa. Sulfasalazine reduced both intestinal inflammation and blood loss, whereas the other DMARDs did not. CONCLUSION: The small intestine is the main site of mild chronic blood loss in patients receiving NSAIDs, and this blood loss can be reduced with sulfasalazine treatment.

Aged↗
PubMed1993

Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans.

BACKGROUND: It is not widely appreciated that nonsteroidal anti-inflammatory drugs (NSAIDs) may cause damage distal to the duodenum. We reviewed the adverse effects of NSAIDs on the large and small intestine, the clinical implications and pathogenesis. METHODS: A systematic search was made through Medline and Embase to identify possible adverse effects of NSAIDs on the large and small intestine. RESULTS: Ingested NSAIDs may cause a nonspecific colitis (in particular, fenemates), and many patients with collagenous colitis are taking NSAIDs. Large intestinal ulcers, bleeding, and perforation are occasionally due to NSAIDs. NSAIDs may cause relapse of classic inflammatory bowel disease and contribute to serious complications of diverticular disease (fistula and perforation). NSAIDs may occasionally cause small intestinal perforation, ulcers, and strictures requiring surgery. NSAIDs, however, frequently cause small intestinal inflammation, and the associated complications of blood loss and protein loss may lead to difficult management problems. The pathogenesis of NSAID enteropathy is a multistage process involving specific biochemical and subcellular organelle damage followed by a relatively nonspecific tissue reaction. The various possible treatments of NSAID-induced enteropathy (sulphasalazine, misoprostol, metronidazole) have yet to undergo rigorous trials. CONCLUSIONS: The adverse effects of NSAIDs distal to the duodenum represent a range of pathologies that may be asymptomatic, but some are life threatening.

Animals↗
PubMed1993

Gastro-duodenal damage due to non-steroidal anti-inflammatory drugs in children.

Thirteen juvenile chronic arthritis patients with abdominal symptoms related to non-steroidal anti-inflammatory drug therapy were endoscoped before and after a 6-week course of either misoprostol or ranitidine therapy. Major presenting symptoms were generalized abdominal pain and nausea. Symptoms did not correlate well with endoscopic findings which revealed no evidence of ulceration and minimal erosive damage. Five patients had mild erythema or gastritis. Bleeding lesions were confined to small numbers of petechiae. Following treatment with either misoprostol or ranitidine, patients improved symptomatically without a corresponding improvement on endoscopic and histological examination of stomach and duodenum. Both treatments were well tolerated.

Adolescent↗
PubMed1992

Metronidazole reduces intestinal inflammation and blood loss in non-steroidal anti-inflammatory drug induced enteropathy.

This study assessed the effect of metronidazole on the gastroduodenal mucosa, intestinal permeability, blood loss, and inflammation in patients on non-steroidal anti-inflammatory drugs (NSAIDs). Thirteen patients were studied before and after 2-12 weeks' treatment with metronidazole 800 mg/day, while maintaining an unchanged NSAID intake. Intestinal inflammation, as assessed by the faecal excretion of indium-111 labelled neutrophils, and blood loss, assessed with chromium-51 labelled red cells, were significantly reduced after treatment (mean (SD) 111In excretion 4.7 (4.7)% v 1.5 (1.3)% (N < 1.0%), p < 0.001, 51Cr red cells loss 2.6 (1.6) ml/day v 0.9 (0.5) ml/day (N < 1.0 ml/day), p < 0.01). Intestinal permeability assessed as the 5 hour urinary excretion ratio of 51CrEDTA/L-rhamnose did not change significantly (0.133 (0.046) v 0.154 (0.064), p > 0.1) and there were no significant changes in the endoscopic or microscopic appearances of the gastroduodenal mucosa. These results suggest that the neutrophil is the main damaging effector cell in NSAID induced enteropathy. The main neutrophil chemo-attractant in this enteropathy may be a metronidazole sensitive microbe.

Aged↗
PubMedDate not supplied

Gastroprotection and nonsteroidal anti-inflammatory drugs (NSAIDS). Rationale and clinical implications.

There is no doubt that nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal injury. The most serious consequences are gastric and duodenal ulcers which can cause bleeding and perforation, and which may lead to the premature death of 3000 to 4000 patients in the UK annually. The immediate actions of NSAIDs operate at a subcellular level; in particular altering of mitochondrial function which causes depletion of ATP and renders the cell vulnerable to oxidant stress. Secondary consequences follow, such as the inhibition of prostaglandin synthesis which delays cellular repair. While adaptation can be shown in volunteers despite continued NSAID ingestion, studies in patients suggest mucosal damage develops continuously and cumulatively even with low doses of aspirin. Histamine H2-receptor antagonists and proton pump inhibitors heal NSAID-related ulcers, though healing rates with H2-antagonists are slower in patients who continue NSAID treatment. They have little role in preventing damage. In addition to acid suppression, prostaglandin analogues cause bicarbonate secretion and enhance mucosal blood flow. They have a specific role in both prevention and treatment of NSAID-related damage. The use of misoprostol offers a rational approach to reduce the high prevalence of unwanted gastroduodenal damage from NSAIDs. On a purely financial basis more information is needed before routine coprescribing can be recommended. However, for any patient on NSAIDs with a previous ulcer or for patients aged over 60 years (where the risks and seriousness of complications are markedly increased), the use of misoprostol should be considered. Further developments in prostaglandin analogues may reduce their adverse effects and perhaps thereby improve their efficacy at symptom control.

Animals↗