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Biomedical subjects

C J Hawkey

Publications and source records attributed to C J Hawkey.

At least 199 records · Page 11Linked to original sources
PubMed1992

Development of biliary sludge in patients on intensive care unit: results of a prospective ultrasonographic study.

Biliary sludge may be a precursor of gall stones in man. The aim of this study was to determine the incidence of biliary sludge in a prospective study of 36 patients admitted to the intensive care unit for longer than two days. The presence of biliary sludge was determined by ultrasonography. Biliary sludge developed in 17 patients (47%), after a mean of 5.5 days in the intensive care unit. Patients who developed biliary sludge spent longer in the intensive care unit (14.2 d (1.3)), compared with patients who did not (8.3 d (1.4)); (p = 0.003). Ten of the patients with biliary sludge had a recognised risk factor: total parenteral nutrition (five), abdominal surgery (two), or both (three). All neurosurgical patients (four) who required total parenteral nutrition developed biliary sludge. Seven patients with biliary sludge had no previously recognised risk factor, five of whom had severe head trauma or neurosurgery. In conclusion, biliary sludge develops frequently and rapidly in patients admitted to an intensive care unit. Neurosurgical procedures are associated with biliary sludge formation. (Sludge is commonly associated with the development of cholestatic liver biochemistry.)

Adolescent↗
PubMed1992

Mechanisms of gastric and duodenal damage and protection.

By binding to the cyclooxygenase enzyme, non-steroidal, anti-inflammatory drugs (NSAIDs) inhibit synthesis of prostanoids characteristic of the cell under consideration. For the gastric mucosa, the main products are prostaglandin (PG) E2 or PGI2; for platelets the main product is thromboxane. Aspirin irreversibly acetylates the cyclooxygenase enzyme. Consequently, it has more prolonged effects, particularly in cells like platelets, which are not rapidly turned over. Prostaglandin-dependent protective actions in the stomach and duodenum which are inhibited by NSAIDs include mucous and bicarbonate secretion, surface epithelial cell hydrophobicity and mucosal blood flow. Prostaglandins are also protective of the microvasculature and can increase the flux of water from serosa to mucosa, with possible dilution of injurious substances. Abrogation of these properties renders the mucosa more vulnerable to injury. In addition, salicylates have topical irritant properties. A number of repair mechanisms, including epithelial cell division and possibly angiogenesis, are prostaglandin dependent. As a consequence of these actions, acute damage and ulcers develop more easily and ulcers heal more slowly when individuals take NSAIDs. In some cases the anti-hemostatic effects of NSAIDs may be partly instrumental, and data in model systems have shown that aspirin and possibly piroxicam can enhance intragastric bleeding separately from their effects of mucosal injury. Smoking, which predisposes to peptic ulceration, also appears to reduce mucosal prostaglandin synthesis. Other predisposing factors such as age, sex and the ulcer diathesis have little effect. Some have found Helicobacter pylori to enhance leukotriene synthesis. We have shown that NSAIDs are also associated with increased leukotriene B4 as well as reduced prostaglandin synthesis in patients taking NSAIDs long term.

Animals↗
PubMed1991

Separation of the impairment of haemostasis by aspirin from mucosal injury in the human stomach.

1. An increasing body of data suggests that the antihaemostatic as well as the ulcerogenic actions of aspirin and other non-steroidal anti-inflammatory drugs may be operative when patients present with haematemesis and melaena. 2. We therefore developed methods to allow separate evaluation of the erosive and anti-haemostatic actions of aspirin in the human gastric mucosa. Volunteer subjects took 300 mg of aspirin daily in the morning or 600 mg of aspirin four times a day for 5 days under blinded randomized conditions. Changes in spontaneous gastric microbleeding, endoscopic signs of injury, spontaneous bleeding per gastric erosion, biopsy-induced bleeding and eicosanoids were studied. 3. Both doses of aspirin significantly inhibited gastric mucosal synthesis of prostaglandin E2 and reduced the serum thromboxane concentration. Erosions developed and regressed rapidly; compared with baseline 300 mg of aspirin daily in the morning caused substantial numbers of gastric erosions to develop (mean 5.3, 95% confidence limits 2.7-10.2) but this was significantly less than that caused by 600 mg of aspirin four times a day (10.9, 7.2-16.5, P less than 0.05). The presence of erosions was associated with enhanced spontaneous bleeding, but only during aspirin administration. 4. Aspirin significantly increased bleeding induced by mucosal biopsy and was associated with significant enhancements in the rate of bleeding per gastric erosion. Bleeding rate per erosion but not biopsy-induced bleeding showed a significant dose-related increase with 600 mg of aspirin four times a day. Enteric coating reduced endoscopic signs of injury, but did not affect the impaired haemostasis caused by aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

A comparison of roxatidine and ranitidine for the acute treatment of duodenal ulcer.

Roxatidine acetate is a new histamine H2-antagonist of about twice the potency of ranitidine on a weight-for-weight basis. Two hundred and thirty-two patients participated in a double-blind randomized trial of duodenal ulcer healing comparing 300 mg ranitidine nocte with 150 mg roxatidine nocte. Endoscopy was repeated fortnightly to 4 weeks in each of four participating centres. Usual exclusion criteria applied but NSAID users were allowed. There were no important demographic differences between treatment recipients. Three analyses were used: protocol (dropouts and violators not included), intention-to-treat I (dropouts considered failures), and intention-to-treat II (dropouts considered failures, but violators outcome included). Healing rates differed markedly (but not significantly) with each analysis. After 2 weeks of treatment ulcers had healed in 51% versus 45% using the intention to treat I analysis with roxatidine and ranitidine, respectively; by the protocol analysis the healing proportions were 60% and 55%. These differences between treatments were not significant. After 4 weeks of treatment healing rates ranged from 71% to 83% on roxatidine and between 69% and 84% on ranitidine depending on the analysis. Differential healing proportions of smokers and non-smokers were non-significant (83% vs. 79%). Both drugs were well tolerated and adverse events were similar with each agent. Roxatidine should prove as effective as ranitidine for acute duodenal ulcer treatment.

Adult↗
PubMed1991

Aspirin-induced gastric mucosal damage: prevention by enteric-coating and relation to prostaglandin synthesis.

1. Gastric damage induced by low-dose aspirin and the protective effect of enteric-coating was assessed in healthy volunteers in a double-blind placebo-controlled cross-over trial using Latin square design. Each was administered placebo, plain aspirin 300 mg daily, plain aspirin 600 mg four times daily, enteric-coated aspirin 300 mg daily, or enteric-coated aspirin 600 mg four times daily for 5 days. Gastric damage was assessed endoscopically, and gastric mucosal bleeding measured. 2. Aspirin 300 mg daily and 600 mg four times daily caused significant increases in gastric injury compared with placebo. Gastric mucosal bleeding was significantly more with the high dose, with a trend towards increased gastric erosions, compared with the low dose. 3. Enteric-coating of aspirin eliminated the injury caused by low dose aspirin and substantially reduced that caused by the higher dose. 4. All dosages and formulations caused similar inhibition of gastric mucosal prostaglandin E2 synthesis. 5. Serum thromboxane levels were suppressed equally with plain and enteric-coated aspirin. 6. In this short-term study in healthy volunteers, gastric toxicity from aspirin was largely topical, independent of inhibition of prostaglandin synthesis, and could be virtually eliminated by the use of an enteric-coated preparation.

Adult↗
PubMed1991

5-Aminosalicylic acid is a potent inhibitor of interleukin 1 beta production in organ culture of colonic biopsy specimens from patients with inflammatory bowel disease.

Interleukin 1 beta in biopsy specimens from inflamed colonic mucosa of patients with active inflammatory bowel disease was studied. Compared with normal colonic mucosal biopsy specimens, a significantly greater amount of interleukin 1 beta was present in rectal mucosa before (median (range) 4.3 (2.0-11.8) v 119.2 (30.1-286.8) pg/mg; p less than 0.01) and produced during organ culture (39.1 (9.4-106.8) v 97.6 (28.2-991.6) pg/mg; p less than 0.01). Values of interleukin 1 beta after culture correlated with concentrations of thromboxane B2. Organ culture of inflamed biopsy specimens in the presence of 5 aminosalicylic acid and dexamethasone reduced the amount of interleukin 1 beta detected. At the doses studied, 5 aminosalicylic acid also reduced the amount of leukotriene B4 detected after culture.

Adult↗
PubMed1991

High circulating concentrations of interleukin-6 in active Crohn's disease but not ulcerative colitis.

Peripheral venous plasma concentrations of interleukin-6 were studied in 21 patients with active Crohn's disease, 20 patients with ulcerative colitis, and 16 control subjects. Interleukin-6 was detected in the plasma of 18 of 21 patients with Crohn's disease (median 47 (range less than 20-250) pg/ml) but in only two with ulcerative colitis and two control subjects. In the patients with Crohn's disease there was a significant negative correlation between the plasma interleukin-6 and the serum albumin concentrations. In eight patients with Crohn's disease and five patients with ulcerative colitis undergoing resection plasma from peripheral circulation and mesenteric vein draining diseased intestine was studied. Interleukin-6 was detected in seven of eight peripheral and mesenteric samples from the patients with Crohn's disease but was not detected in any of the samples from the patients with ulcerative colitis. There was no significant difference between mesenteric and peripheral samples in the concentrations of interleukin-6.

Adolescent↗
PubMed1990

Effect of reactive pharmacy intervention on quality of hospital prescribing.

OBJECTIVE: To evaluate the medical impact of reactive pharmacy intervention. DESIGN: Analysis of all interventions during 28 days by all 35 pharmacists in hospitals in Nottingham. SETTING: All (six) hospitals in the Nottingham health authority (a teaching district), representing 2530 mainly acute beds, 781 mental illness beds, and 633 mainly health care of the elderly beds. PATIENTS: Hospital inpatients and outpatients. INTERVENTIONS: Recording of every important intervention made by pharmacists to prescriptions for both inpatients and outpatients when they perceived inadequacies of drug prescription or administration, including characterisation of the problem, coding of outcome, recording of time taken to initiate and resolve intervention, and grade of prescribing doctor. The problems were independently assessed for their potential to cause medical harm. RESULTS: 769 Interventions (about 2.9% of prescriptions) were made, of which 60 concerned prescriptions rated as having a major potential for medical harm. The commonest problems concerned dosage, which was wrong in 280 prescriptions (102 for antibiotics) and not stated in 50 (one for antibiotics), especially those associated with a major potential for medical harm (32 prescriptions). These concerned sedatives; analgesics; cardiovascular drugs or diuretics; and iron, vitamin, or mineral preparations. Also common were overprolonged prescription of antibiotics (48 prescriptions), confusion of drug names (nine), and inadvertent coprescription of excessive quantities of aspirin or paracetamol in plain and compound preparations (seven). The pharmacist's recommendation was accepted in 639 instances (86%), and the prescription was altered in 575, leading to an appreciable (246 cases) or minor (231 cases) improvement. Interventions had little effect on costs; 427/646 had no effect and 130 produced savings less than 50p. Pharmacy intervention (730/769 interventions) occupied on average 41 minutes per pharmacist per week. CONCLUSIONS: Most reactive pharmacy interventions concerned prescribing errors with a limited potential for medical harm, but a small number of detected errors with a major potential for medical harm; cost savings were not appreciable.

Decision Making↗
PubMed1990

High dose eicosapentaenoic acid ethyl ester: effects on lipids and neutrophil leukotriene production in normal volunteers.

1. A 93% pure ethyl ester of eicosapentaenoic acid was investigated for tolerability and biochemical effects on neutrophil leukotriene synthesis and plasma lipoproteins when given in high dose. Six healthy volunteers received 6 g eicosapentaenoic acid ethyl ester daily for 6 weeks, followed by a 4 week wash-out and then 18 g daily for 6 weeks. 2. There was inhibition of neutrophil leukotriene B4 and 5-hydroxyeicosatetraenoic acid synthesis, with no significant differences between low and high dose. 3. There was a dose dependent increase in leukotriene B5 and 5-hydroxyeicosatetraenoic acid acid synthesis. 4. Plasma triglycerides were reduced maximally on 6 g daily, with no greater suppression at 18 g daily. 5. Plasma cholesterol was only suppressed significantly at 18 g daily. 6. The 6 g daily dose was well tolerated but the 18 g daily dose produced diarrhoea and steatorrhoea.

Adult↗
PubMed1990

Plasma and tissue interleukin-2 receptor levels in inflammatory bowel disease.

Plasma and tissue interleukin-2 receptor (IL-2R) levels were determined in patients with active ulcerative colitis and Crohn's disease. Compared with healthy controls (median 440 U/ml; range 240-900), significantly higher levels of plasma IL-2R were present in patients with active ulcerative colitis (median 1180 U/ml; range 580-7150; P less than 0.002) and Crohn's disease (median 1340 U/ml; range 480-9000; P less than 0.002). Compared with other laboratory parameters, plasma IL-2R levels were related most closely to clinical score of disease activity in Crohn's disease. Plasma IL-2R levels also reflected the clinical course and may provide a more accurate assessment of disease activity in Crohn's disease. In plasma of patients undergoing intestinal resection of active inflammatory bowel disease, raised levels of IL-2R were present in samples from mesenteric vein (draining inflamed intestine) compared with those from peripheral vein. In tissue homogenates of colonic biopsies, significantly higher levels of IL-2R were present in specimens from colons with active ulcerative colitis compared with healthy controls (median 230.2, range 20.7-581.5 versus 77.9, range 34.2-291.3; P less than 0.02).

Biopsy↗
PubMed1990

Abolition by omeprazole of aspirin induced gastric mucosal injury in man.

This study investigates whether aspirin injury to the human gastric mucosa can be prevented by profound acid suppression with omeprazole, in a randomised, double blind, crossover design according to latin square. It was concluded that profound acid suppression can prevent aspirin induced gastric mucosal injury in normal subjects. This approach may prevent the development of peptic ulcers and their complications in patients taking aspirin and other non-steroidal anti-inflammatory drugs.

Adult↗
PubMed1989

Human gastric mucosal bleeding induced by low dose aspirin, but not warfarin.

OBJECTIVE: To investigate the suitability of treatment with low dose aspirin or warfarin, or both, as possible prophylaxis against cardiovascular disease by determining the effect on gastric mucosal bleeding. DESIGN: Randomised crossover trial. SETTING: Academic department of therapeutics. SUBJECTS: Twenty healthy male volunteers aged 19-22. INTERVENTIONS: On separate occasions and in randomised order all subjects received aspirin 75 mg, warfarin, or aspirin 75 mg combined with warfarin. Each treatment was given for 12 days or (when warfarin was used) for longer if necessary until the international normalised ratio of the prothrombin time was stable at 1.4-1.6. END POINT: Loss of blood over 10 minutes into gastric washings. MEASUREMENTS AND MAIN RESULTS: Bleeding over 10 minutes into gastric washings under baseline conditions and after five days, and at end of each regimen of treatment. Aspirin 75 mg increased bleeding from 0.60 (95% confidence interval 0.36 to 0.99) microliters/10 minutes to 1.26 (0.71 to 2.25) microliters/10 minutes at five days, with no evidence of either progressive change or adaptation thereafter. Warfarin had no effect on bleeding either alone or when combined with aspirin. CONCLUSIONS: Aspirin 75 mg causes gastric mucosal bleeding. Low dose warfarin neither induces gastric mucosal bleeding nor enhances that caused by aspirin.

Adult↗
PubMed1989

Use of microbleeding and an ultrathin endoscope to assess gastric mucosal protection by famotidine.

We have developed an ultrathin endoscope for repeated endoscopy in unsedated subjects and used it with assessment of bleeding rates to investigate aspirin-induced gastric mucosal injury and its prevention by famotidine. Compared with placebo, 900 mg of aspirin b.i.d. taken for 48 h caused significant endoscopic injury (median grade 3.5, interquartile range 2-4, modified Lanza scale, p less than 0.01), with an increase in mucosal bleeding from 2.0 (geometric mean; 95% confidence limits, 1.1-3.9) microliters/12 min, to 8.3 (2.4-28.8) microliters/12 min (p less than 0.05). Famotidine (20 mg b.i.d.) raised intragastric pH and reduced endoscopic antral injury (median 1.5, interquartile range 0.5-2, p less than 0.05) and bleeding [3.1 (1.2-8.3) microliters/12 min, p less than 0.01] to levels not significantly different from placebo [1 (0-1) and 2.0 (1.1-3.9) microliters/12 min, respectively]. By contrast, 2 mg of famotidine b.i.d. had no significant effect on intragastric pH endoscopic injury or bleeding rates. The two assessments of gastric mucosal injury correlated strongly (r = 0.71, p less than 0.01). The reduction in bleeding with famotidine tended to be higher, the greater the intragastric pH (r = 0.66, p = 0.057). Ultrathin endoscopy is a simple technique that validates gastric mucosal bleeding as a measure of acute gastric mucosal injury in humans. Acid suppression is an effective method of ameliorating this injury.

Adolescent↗
PubMed1989

Nature and time-course of piroxicam-induced injury to human gastric mucosa.

The nature and time-course of acute piroxicam-induced gastric mucosal injury was determined in ten healthy volunteers treated with 10 mg piroxicam twice daily by mouth for 21 days. Mucosal injury was measured endoscopically by visual analogue scales and by the method of Lanza, and luminal blood loss by haemoglobin measurements in gastric washings, 10 h after the first drug dose and then after 5, 10 and 21 days. Acute mucosal injury, consisting mainly of haemorrhagic lesions in the gastric body, developed to a maximum extent within 10 h of the first dose of piroxicam, and did not increase thereafter. By contrast intraluminal bleeding increased little for 10 days and then rose significantly at 21 days, when plasma piroxicam levels reached values likely to affect platelet function. We conclude that gastric mucosal injury and bleeding may be dissociated and may constitute different targets for prophylaxis. Gastric mucosal injury is probably exerted topically as it is maximal at low plasma drug concentrations, whereas bleeding may arise because of interference with platelet-dependent mechanisms.

Adult↗
PubMed1989

Failure of ethamsylate to reduce aspirin-induced gastric mucosal bleeding in humans.

1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3. At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reaction. 4. Aspirin increased bleeding from a rate on placebo of 1.2 microliters 10 min-1 geometric mean (95% confidence limits) (0.7-1.8) microliters 10 min-1 to 20.0 (11.6-34.2) microliters 10 min-1, (P less than 0.01). The rate of bleeding after aspirin preceded by ethamsylate [14.1 (8.5-23.4) microliters 10 min-1] was not significantly different from that after aspirin alone. 5. We conclude that ethamsylate does not reduce acute aspirin-induced gastric mucosal bleeding in healthy humans.

Adult↗