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Biomedical subjects

C Hawkey

Publications and source records attributed to C Hawkey.

At least 19 recordsLinked to original sources
PubMed2004

Reduced incidence of gastroduodenal ulcers associated with lumiracoxib compared with ibuprofen in patients with rheumatoid arthritis.

BACKGROUND: Lumiracoxib (Prexige; Novartis Pharma AG, Basel, Switzerland) is a cyclooxygenase-2 selective inhibitor associated with improved gastrointestinal safety compared with nonsteroidal anti-inflammatory drugs, in patients with osteoarthritis. AIM: To compare the gastroduodenal safety of lumiracoxib with ibuprofen and celecoxib in patients with rheumatoid arthritis. METHODS: A total of 893 patients with rheumatoid arthritis were randomized to lumiracoxib 400 mg once daily, lumiracoxib 800 mg once daily, ibuprofen 800 mg three times daily or celecoxib 200 mg twice daily for 13 weeks, in a double-blind randomised controlled clinical trial. The primary endpoint was the cumulative incidence of gastroduodenal ulcers over 13 weeks. RESULTS: The incidence of gastroduodenal ulcers >/=3 mm with lumiracoxib 400 mg once daily (2.8%) or lumiracoxib 800 mg once daily (4.3%) was significantly lower than with ibuprofen (13.6%, all P < 0.01) and not different from celecoxib (1.9%). The incidence of adverse events was similar for lumiracoxib 400, 800 mg and celecoxib (78, 75 and 77%, respectively) and higher with ibuprofen (86%). Discontinuation for adverse events was highest for ibuprofen (12.5% vs. 7.9-8.8% for the other groups). CONCLUSIONS: Lumiracoxib demonstrated gastroduodenal safety superior to ibuprofen and similar to celecoxib in patients with rheumatoid arthritis.

Adolescent↗
PubMed2001

An engineered human antibody to TNF (CDP571) for active Crohn's disease: a randomized double-blind placebo-controlled trial.

BACKGROUND & AIMS: We evaluated CDP571, a humanized antibody to tumor necrosis factor, for the treatment of active Crohn's disease. METHODS: One hundred sixty-nine patients with moderate-to-severe Crohn's disease were enrolled in a 24-week placebo-controlled trial. Patients were initially randomized to a single dose of 10 or 20 mg/kg CDP571 or placebo to assess dose response. Patients were then retreated with 10 mg/kg CDP571 or placebo every 8 or 12 weeks to assess subsequent dosing intervals. The primary endpoint was clinical response at week 2, defined as a decrease in the Crohn's Disease Activity Index score > or = 70 points. RESULTS: At week 2, clinical response occurred in 45% of CDP571-treated patients compared with 27% of patients in the placebo group (P = 0.023). Patients appeared to benefit from retreatment with CDP571 over 24 weeks, but not all of the results for secondary endpoints were statistically significant. The frequency of severe or serious adverse events was similar among all groups. CONCLUSIONS: CDP571 at an initial dose of 10 or 20 mg/kg is safe and effective for treatment of patients with moderate-to-severe Crohn's disease. Preliminary evidence suggests that retreatment with 10 mg/kg CDP571 at dose intervals of 8 or 12 weeks may also be beneficial, but additional studies are needed.

Adolescent↗
PubMed2001

Quality of life in chronic NSAID users: a comparison of the effect of omeprazole and misoprostol.

OBJECTIVE: To compare the impact on quality of life (QoL) of omeprazole and misoprostol during healing, and omeprazole, misoprostol, and placebo during maintenance treatment in chronic NSAID users with NSAID-associated gastroduodenal lesions. METHODS: Validated baseline and follow-up QoL questionnaires were completed by 610 patients (healing: after 4/8 weeks; maintenance: after 6 months). RESULTS: Patients with arthritis being treated with NSAIDs have a poor QoL. Rheumatoid arthritis causes more joint problems and physical mobility limitations than osteoarthritis. Chronic NSAID use causes heartburn and dyspepsia. QoL improved on both treatments (about equally on two general QOL scales), but omeprazole relieved gastrointestinal symptoms more than misoprostol, particularly reflux, abdominal pain and indigestion symptoms. During maintenance, both treatments maintained QoL, but misoprostol induced diarrhoea. CONCLUSION: QoL in arthritis patients on chronic NSAID treatment is destroyed. Omeprazole is superior to misoprostol for relief and prevention of NSAID-associated gastrointestinal symptoms allowing continued NSAID treatment without compromising the patients' QoL.

Adolescent↗
PubMed2000

Prospective study of potentially virulent strains of Helicobacter pylori and coronary heart disease in middle-aged men.

BACKGROUND: Studies are needed to test claims that potentially virulent strains of Helicobacter pylori are more strongly related to coronary heart disease (CHD) than are other strains. METHODS AND RESULTS: We measured serum IgG antibodies to mixed H pylori antigens and separately to the virulence-associated H pylori antigen CagA (cytotoxin-associated gene product A) in 505 CHD cases and in 1025 age-matched controls "nested" in a prospective study of 7735 British men (mean duration of follow-up in controls, 16 years). Of the 505 cases, 401 (79%) were seropositive for H pylori antibodies compared with 740 (72%) of the 1025 controls, yielding an odds ratio for CHD of 1.55 (95% CI 1.19 to 2.03), which fell to 1.30 (95% CI 0.88 to 1. 90) after adjustments were made for standard vascular risk factors and indicators of socioeconomic status. Of the CHD cases, 240 (48%) were seropositive for IgG antibodies to CagA compared with 450 (44%) of the controls. When CagA-seropositive individuals were compared with H pylori-seronegative individuals, the odds ratio for CHD was 1. 42 (95% CI 1.06 to 1.91), which fell to 1.10 (95% CI 0.71 to 1.71) after adjustments. In an analysis restricted to the 1141 (75%) H pylori-seropositive participants, the odds ratio for CHD was 1.0 (95% CI 0.78 to 1.29) in CagA-seropositive men. No strong associations were observed between H pylori seropositivity and blood lipids, blood pressure, markers of systemic inflammation, or plasma homocysteine. CONCLUSIONS: H pylori infection is not strongly related to the incidence of CHD in late middle-aged men, and CagA-positive strains appear to be no more strongly related to the disease than other strains. However, further studies are required to confirm or refute the existence of any moderate associations, particularly at younger ages.

Antibodies, Bacterial↗
PubMed2000

Comparison of the effect of rofecoxib (a cyclooxygenase 2 inhibitor), ibuprofen, and placebo on the gastroduodenal mucosa of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial. The Rofecoxib Osteoarthritis Endoscopy Multinational Study Group.

OBJECTIVE: This randomized, double-blind study tested the hypothesis that rofecoxib, a drug that specifically inhibits cyclooxygenase 2, would cause fewer gastroduodenal ulcers than ibuprofen (in a multicenter trial), and its side effects would be equivalent to those of placebo (in a prespecified analysis combining the results with another trial of identical design). METHODS: Seven hundred seventy-five patients with osteoarthritis were randomized to receive rofecoxib at a dosage of 25 mg or 50 mg once daily, ibuprofen 800 mg 3 times daily, or placebo. Gastroduodenal ulceration was assessed by endoscopy at 6, 12, and (for active treatment) 24 weeks. The primary and secondary end points were the incidence of gastroduodenal ulcers at 12 and 24 weeks, respectively. RESULTS: Ulcers were significantly less common (P < 0.001) following treatment with rofecoxib (25 mg or 50 mg) than with ibuprofen after 12 weeks (5.3% and 8.8% versus 29.2%, respectively) or 24 weeks (9.9% and 12.4% versus 46.8%, respectively). In the combined analysis, the 12-week ulcer incidence with 25 mg rofecoxib (4.7%) and with placebo (7.3%) satisfied prespecified criteria for equivalence. CONCLUSION: At 2-4 times the therapeutically effective dose, rofecoxib caused fewer endoscopically detected ulcers than did ibuprofen. Rofecoxib at a dose of 25 mg (the highest dose recommended for osteoarthritis) satisfied prespecified criteria for equivalence to placebo.

Cyclooxygenase Inhibitors↗
PubMed2000

High prevalence of potentially virulent strains of Helicobacter pylori in the general male British population.

BACKGROUND: Strains of Helicobacter pylori that express the cytotoxin associated gene product A (CagA) may be more strongly associated with serious gastric diseases, such as gastric cancer and peptic ulceration, than other strains. Data, however, are sparse on the prevalence, risk factors, and other correlates of these strains in the general population. AIM: To characterise aspects of the seroepidemiology of CagA(+) strains of H pylori in the general British population. METHODS: We measured serum IgG antibodies to mixed H pylori antigens and separately to CagA in 1025 men aged 40-59 years who were randomly selected from a larger group of participants in a community based survey conducted in 18 different British towns. RESULTS: Overall, 44% (95% confidence interval 41-47%) of the men were seropositive to CagA antibodies, representing about 61% (57-65%) of the men seropositive to mixed antigen H pylori. The risk factors for seropositivity to CagA antibodies were similar to those for seropositivity to mixed antigen H pylori, apart from an increased prevalence of reported bedroom sharing in childhood (p<0.01). CONCLUSION: In a nationwide study of potentially virulent H pylori strains, there was a high prevalence of the infection, with some evidence that acquisition of such strains might occur earlier in life than other strains.

Aged↗
PubMed1998

Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients. International MELISSA Study Group. Meloxicam Large-scale International Study Safety Assessment.

Although widely used, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with a high incidence of gastrointestinal (GI) side-effects. Inhibition of the cyclooxygenase (COX) enzyme is the basis for both the efficacy and toxicity of NSAIDs. The discovery of two COX isoforms, constitutive COX-1 and inducible COX-2, has led to the hypothesis that selective inhibition of COX-2 will minimize the potential for GI toxicity without compromising efficacy. The Meloxicam Large-scale International Study Safety Assessment (MELISSA) trial reported here was therefore set up to investigate the tolerability of meloxicam, a preferential inhibitor of COX-2, compared to diclofenac. MELISSA was a large-scale, double-blind, randomized, international, prospective trial, conducted over 28 days in patients with symptomatic osteoarthritis. Patients received either meloxicam 7.5 mg or diclofenac 100 mg slow release, the recommended doses for the treatment of osteoarthritis. Evaluation of the profile of adverse events was the main aim of the trial, together with assessment of efficacy. A total of 9323 patients received treatment (4635 and 4688 in the meloxicam and diclofenac groups, respectively). Significantly fewer adverse events were reported by patients receiving meloxicam. This was attributable to fewer GI adverse events (13%) compared to diclofenac (19%; P < 0.001). Of the most common GI adverse events, there was significantly less dyspepsia (P < 0.001), nausea and vomiting (P < 0.05), abdominal pain (P < 0.001) and diarrhoea (P < 0.001) with meloxicam compared to diclofenac. Five patients on meloxicam experienced a perforation, ulcer or bleed vs seven on diclofenac (not significant). No endoscopically verified ulcer complication was detected in the meloxicam group compared to four with diclofenac. There were five patient days of hospitalization in patients on meloxicam compared to 121 with diclofenac. Adverse events caused withdrawal from the study in 254 patients receiving meloxicam (5.48%) compared to 373 (7.96%) on diclofenac (P < 0.001). These differences were attributable to differences in reported GI adverse events (3.02% on meloxicam vs 6.14% on diclofenac; P < 0.001). Differences in efficacy, as assessed by visual analogue scales, consistently favoured diclofenac. In all instances, 95% confidence intervals did not cross zero, suggesting a statistically significant effect. However, differences were small (4.5-9.01% difference) and did not reach pre-determined levels of clinical significance. Nevertheless, significantly more patients discontinued meloxicam because of lack of efficacy (80 out of 4635 vs 49 out of 4688; P < 0.01). The MELISSA trial confirms earlier studies suggesting that meloxicam has a significantly improved GI tolerability profile in comparison with other NSAIDs, including diclofenac. These results may in part reflect the preferential COX-2 selectivity of meloxicam, although the dose and other aspects of tolerability may be important. These results may provide support for the hypothesis that selective inhibition of COX-2 relative to COX-1 might be an effective approach towards improved NSAID therapy.

Aged↗
PubMed1998

Improvement in gastrointestinal tolerability of the selective cyclooxygenase (COX)-2 inhibitor, meloxicam, compared with piroxicam: results of the Safety and Efficacy Large-scale Evaluation of COX-inhibiting Therapies (SELECT) trial in osteoarthritis.

SELECT is a large-scale, prospective, international, multicentre, double-blind, double-dummy, randomized, parallel-group trial. Patients with exacerbation of osteoarthritis were treated with the recommended dose of meloxicam (7.5 mg) or piroxicam (20 mg) once daily for 28 days; 4320 patients were administered meloxicam and 4336 piroxicam. The incidence of adverse events was significantly lower in the meloxicam group (22.5%) compared with the piroxicam group (27.9%; P < 0.001), mainly due to the significantly lower incidence of gastrointestinal (GI) adverse events in the meloxicam than in the piroxicam group (10.3% vs 15.4%,; P < 0.001), while the efficacy of both drugs was equivalent. Individual GI events occurred significantly less often with meloxicam than piroxicam: dyspepsia (3.4% vs 5.8%; P < 0.001), nausea/vomiting (2.5% vs 3.4%; P < 0.05) and abdominal pain (2.1% vs 3.6%; P < 0.001). There were 16 patients with perforations, ulcerations or bleeding (PUBs) of the upper GI tract in the piroxicam group compared with seven in the meloxicam group (relative risk piroxicam:meloxicam = 1.4). Four PUBs were complicated (perforations or bleedings); none of these occurred in the meloxicam group (relative risk piroxicam:meloxicam = 1.9). The outcome of SELECT is consistent with that of the large-scale clinical trial of similar design and size which compared 7.5 mg meloxicam with 100 mg diclofenac in patients with osteoarthritis, and with a previous global analysis of the safety of meloxicam. It adds further data to the proposed relationship between selective inhibition of cyclooxygenase-2 and improved GI tolerability of non-steroidal anti-inflammatory drugs.

Aged↗
PubMed1996

Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis.

OBJECTIVE: To compare the relative risks of serious gastrointestinal complications reported with individual non-steroidal anti-inflammatory drugs. DESIGN: Systematic review of controlled epidemiological studies that found a relation between use of the drugs and admission to hospital for haemorrhage or perforation. SETTING: Hospital and community based case-control and cohort studies. MAIN OUTCOME MEASURES: (a) Estimated relative risks of gastrointestinal complications with use of individual drugs, exposure to ibuprofen being used as reference; (b) a ranking that best summarised the sequence of relative risks observed in the studies. RESULTS: 12 studies met the inclusion criteria. 11 provided comparative data on ibuprofen and other drugs. Ibuprofen ranked lowest or equal lowest for risk in 10 of the 11 studies. Pooled relative risks calculated with exposure to ibuprofen used as reference were all significantly greater than 1.0 (interval of point estimates 1.6 to 9.2). Overall, ibuprofen was associated with the lowest relative risk, followed by diclofenac. Azapropazone, tolmetin, ketoprofen, and piroxicam ranked highest for risk and indomethacin, naproxen, sulindac, and aspirin occupied intermediate positions. Higher doses of ibuprofen were associated with relative risks similar to those with naproxen and indomethacin. CONCLUSIONS: The low risk of serious gastrointestinal complications with ibuprofen seems to be attributable mainly to the low doses of the drug used in clinical practice. In higher doses ibuprofen is associated with a similar risk to other non-steroidal anti-inflammatory drugs. Use of low risk drugs in low dosage as first line treatment would substantially reduce the morbidity and mortality due to serious gastrointestinal toxicity from these drugs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Two comparative endoscopic evaluations of Naprelan.

This paper describes the results of two endoscopic studies of Naprelan (Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania), a controlled-release formulation of naproxen sodium. In one study, 19 healthy male subjects received either 2 controlled release Naprelan 500-mg tablets once daily or 1 Naprosyn (naproxen; Syntex Laboratories, Inc., Palo Alto, California) 500-mg tablet BID. At baseline, all subjects had gastroduodenal endoscopy scores of 0 on both the Lanza and Euler scales. Although the trend favored Naprelan, differences in Lanza and Euler scale elevations were not statistically significant. Eight of 10 subjects in the Naprelan group and 7 of 9 subjects in the Naprosyn group reported a total of 27 adverse events (AEs). In the second study, healthy subjects received Naprelan 1,000 mg once daily, Naprosyn 500 mg BID, and film-coated aspirin 650 mg QID. In the stomach, there was a significant difference in favor of Naprelan over aspirin (P = 0.0001) and in favor of Naprosyn over aspirin (P = 0.0001). Fewer erosions were seen in the duodenum than in the stomach. In the duodenum, there was a significant difference in favor of Naprelan over Naprosyn (P = 0.0236), and in favor of Naprelan over aspirin (P = 0.0086), but the difference between Naprosyn and aspirin was not significant (P = 0.6643). Of the 23 subjects who received medication, 12 reported AEs: 8 while receiving aspirin, 3 while receiving Naprosyn, and 1 while receiving Naprelan. Differences in the number of erosions and ulcers seen following each of the periods of drug administration favored Naprelan and the Intestinal Protective Drug Absorption System.

Adolescent↗
PubMed1995

Hematology of fledgling Manx shearwaters (Puffinus puffinus) with and without 'puffinosis'.

Hematological parameters were measured in 14 fledgling Manx shearwaters (Puffinus puffinus), with the disease puffinosis and in 10 birds that did not have the disease, on the Island of Skomer between 2 and 11 September 1991. The mean plasma fibrinogen concentration was significantly higher in the diseased birds and some of these had abnormally elevated monocyte counts. No other significant differences were observed.

Animals↗
PubMed1991

The effect of dietary change on in vitro erythrocyte haemolysis, skin lesions and alopecia in common marmosets (Callithrix jacchus).

1. The effect of dietary change on common marmosets (Callithrix jacchus) exhibiting high in vitro erythrocyte haemolysis, skin lesions and alopecia was investigated. 2. The experimental diet was low in lipid, high in vitamin E and was devoid of n-3 long chain polyunsaturated fatty acids. 3. There were significant increases in the concentrations of plasma alpha-tocopherol (vitamin E) (P less than 0.05), all-trans retinol (vitamin A) (P less than 0.001) and total lipid (P less than 0.025), and a reduction in fibrinogen (P less than 0.02) concentration and neutrophil count (P less than 0.02). 4. Moreover, the mean in vitro erythrocyte haemolysis declined from an initial value of 64% to less than 2%, and there was a regression of skin lesions and alopecia with complete fur regrowth. 5. The amelioration of the conditions appear to be due to high circulating vitamin E which provided protection against oxidative stress, and the correction of membrane n-6:n-3 balance.

Alopecia↗
PubMed1990

Anaesthesia, movement and emesis.

One hundred and eighty-two women undergoing dilatation and curettage were allocated randomly to receive premedication comprising temazepam, papaveretum-hyoscine or placebo. The temazepam recipients reported significantly fewer episodes of postoperative nausea. Movement was blamed by 66% of patients who identified a cause for nausea. These patients had higher scores on a motion sickness susceptibility questionnaire and were more likely to have been treated previously for nausea or vomiting. It may be possible to identify susceptible patients before surgery.

Adult↗
PubMed1989

Heinz bodies do not modify the membrane characteristics of common marmoset (Callithrix jacchus) erythrocytes.

The possibility was examined that the membrane function of erythrocytes obtained from healthy common marmosets (Callithrix jacchus) was modified by the presence in the cells of Heinz bodies. No significant differences were found in erythrocyte endogenous free malonyl dialdehyde (MDA) or reduced glutathione (GSH) between normal human erythrocytes and marmoset erythrocytes containing Heinz bodies. Membrane fluorescent chromolipids, surface charge and thiol levels were similar in both species but average membrane bulk lipid fluidity was slightly elevated in the marmosets. It was concluded that, in contrast to the situation in human erythrocytes, the presence of Heinz bodies in red cells of marmosets does not adversely affect the properties of the membrane.

Animals↗
PubMed1988

The effect of dietary fatty acids on the gastric production of prostaglandins and aspirin-induced injury.

We have investigated in man the effect of dietary supplementation with evening primrose oil (linoleic acid 72%, gamma-linolenic acid 9%) on gastric immunoreactive PGE2 release and aspirin-induced mucosal injury. Twenty healthy volunteers received in a randomized crossover evening primrose oil (2 g b.d.) and olive oil (control) for 2 weeks each. During the last 48 hours of each period, five doses of aspirin 900 mg were taken. In gastric washings on day 7, evening primrose oil had enhanced immunoreactive PGE2 release from a mean of 38 ng/30 min (olive oil) to 80 ng/30 min (P less than 0.05). This, however, was not able to protect against aspirin-induced gastric blood loss which rose from a mean (95% confidence limits) of 1.3 (0.7-2.1) microliters 10 min-1 (evening primrose oil day 7) to 9.4 (5.4-16.5) microliters 10 min-1 (day 14). Although not effective against aspirin, similar dietary supplementation might assist in preventing peptic ulcer recurrence.

Adult↗