PubMed Health⌕ Search

Biomedical subjects

P J Prichard

Publications and source records attributed to P J Prichard.

17 recordsLinked to original sources
PubMed1998

Colorectal cancer.

Colorectal cancer is the leading cause, after lung cancer, of death from cancer in Australia. About 50% of colorectal cancers are attributed to dietary factors and about 15%-20% to genetic factors, including high risk familial syndromes. The most common presenting symptoms are rectal bleeding (left-sided cancers) and iron-deficiency anaemia (right-sided cancers). Patients with suggestive symptoms should have a digital rectal examination, followed by sigmoidoscopy and biopsy if a rectal lesion is suspected, or colonoscopy if colon cancer is suspected. Treatment of most colorectal cancers is segmental resection with a wide resection margin; the role of adjuvant therapy is still being refined. Screening with annual (or biennial) faecal occult blood tests is recommended for people over 50 years without symptoms and with average or slightly above average risk; more intensive, earlier screening is recommended for those with greater risk.

Colectomy↗
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

Enhanced gastric mucosal bleeding with doses of aspirin used for prophylaxis and its reduction by ranitidine.

1. We evaluated injury to the human gastric mucosa caused by low doses of aspirin and its prophylaxis by ranitidine. On two separate occasions, 30 subjects took aspirin 300 mg daily for 12 days either with or without ranitidine 150 mg, 30 min before aspirin. This dose of aspirin caused more than a 5 fold increase in gastric bleeding, from control values of 0.5 microliters 10 min-1 (95% confidence limits 0.3-0.8 microliters 10 min-1) to 2.8 microliters 10 min-1 (1.9-4.1 microliters 10 min-1, P less than 0.01) after 5 days of aspirin. Adaptation did not occur and the gastric bleeding rates remained elevated at 3.4 microliters 10 min-1 (1.9-6.1 microliters 10 min-1) after 12 days of aspirin consumption (P less than 0.01). 2. Coadministration of ranitidine significantly raised intragastric pH and reduced aspirin induced bleeding to 1.5 microliters 10 min-1 (1.0-2.3 microliters 10 min-1) after 5 days and 1.6 (1.0-2.5 microliters 10 min-1) after 12 days (P less than 0.05). 3. Although these values were higher than control levels our results raise the possibility that coadministration of ranitidine may reduce the incidence of peptic ulceration and gastrointestinal haemorrhage which is increasingly reported in some subjects taking low dose aspirin for vascular prophylaxis.

Adult↗
PubMed1989

Aspirin and gastroduodenal injury.

Aspirin almost invariably causes acute mucosal injury to the stomach or duodenum as evidenced by erosions seen endoscopically, extensive surface cell disruption on histology, reduced mucosal potential difference and increased gastric bleeding. This injury is usually minor and transient, and not associated with symptoms. However, in the elderly recent aspirin intake may be associated with bleeding peptic ulcer, and along with other NSAIDs, may be causal in a third of cases. Regular chronic aspirin intake may also be associated with gastric ulceration. Such ulceration, however, although seemingly capable of healing despite continued aspirin or other NSAID use, may take longer to do so. Although aspirin and other NSAIDs have a strong connection with gastroduodenal problems the risk in an individual needs to be balanced by the likelihood of such events. Given their widespread use, the serious side effects of these drugs occur in only a small proportion of users. This, however, does not mitigate against careful prescription.

Aspirin↗
PubMed1988

Effect in man of aspirin, standard indomethacin, and sustained release indomethacin preparations on gastric bleeding.

1. We have compared acute gastric bleeding caused by a new slow release preparation of indomethacin (indomethacin Continus) with that caused by aspirin and other indomethacin preparations. 2. In a randomized crossover study, blood loss into timed gastric aspirates was determined in 20 healthy volunteers after receiving, over 96 h, either placebo, aspirin (600 mg four times daily; 17 doses) indomethacin BP (50 mg three times daily; 13 doses), Indocid-R (75 mg twice daily; 9 doses) or indomethacin Continus (75 mg twice daily; 9 doses). A venous blood sample was also taken during each treatment period for subsequent determination of alpha 1-glycoprotein, and for drug assay. 3. Gastric bleeding on placebo was 1.4 (0.7-2.8) microliters 10 min-1 (mean, 95% confidence interval). Both aspirin and the indomethacin preparations caused significantly more bleeding (P less than 0.05). Rates of bleeding after aspirin, indomethacin BP, Indocid-R, and indomethacin Continus were respectively 22.0 (10.7-47.2) microliters 10 min-1, 4.4 (2.2-9.1) microliters 10 min-1, 10.8 (5.3-22.3) microliters 10 min-1, and 5.1 (3.0-10.6) microliters 10 min-1. 4. Rates of bleeding after indomethacin BP and indomethacin Continus, but not Indocid-R, were significantly less than after aspirin (P less than 0.01). 5. Salicylate or indomethacin was detectable in the plasma of all subjects after the active treatment periods, except for one instance involving a subject allocated indomethacin BP. Indomethacin levels were significantly higher 2 h after Indocid-R than with indomethacin BP or indomethacin Continus. 6. alpha 1-acid glycoprotein levels were not significantly affected by prior treatment with aspirin or indomethacin.

Adolescent↗
PubMed1987

Oral phenytoin pharmacokinetics during omeprazole therapy.

1. In a double-blind crossover study 10 healthy males received either placebo or omeprazole (40 mg day-1) for 9 days, a single dose of phenytoin (300 mg) being taken on the seventh day. 2. Omeprazole significantly increased the area under the curve (0 to 72 h) of phenytoin (mean +/- s.e. mean) from 121.6 +/- 14.0 to 151.4 +/- 13.6 micrograms ml-1 h) (P less than 0.01). 3. The peak concentration, and apparent elimination half-life of phenytoin also tended to be increased though not significantly. 4. The omeprazole-phenytoin interaction observed may be clinically important because of the low therapeutic index associated with phenytoin.

Administration, Oral↗
PubMed1986

The effectiveness of ranitidine in reducing gastric acid-secretion decreases with continued therapy.

To examine whether changes in inhibition of gastric acid secretion occur during chronic ranitidine therapy, duodenal ulcer patients in remission were studied before and after 9 months of maintenance ranitidine therapy (150 mg nocte). At each time, the effect of a bolus i.v. dose of ranitidine (50 mg) on pentagastrin-stimulated maximal acid output was measured. Oral and intravenous pharmacokinetic studies were also performed to examine whether changes in absorption or disposition occur during long-term dosage. After 9 months' therapy, ranitidine inhibited pentagastrin-stimulated secretion by a median of 62%, substantially less than the median inhibition of 95% pre-treatment. Median acid output in the period 60-120 min post-ranitidine was six times the pretreatment value. Since pharmacokinetic parameters were unaltered, this reduced ability to inhibit acid output appears to indicate reduced sensitivity of acid secreting mechanisms to ranitidine after prolonged dosage.

Administration, Oral↗
PubMed1986

Strategies for preventing aspirin-induced gastric bleeding.

Prostaglandins protect the gastric mucosa in animals, but the evidence of an effect independent of pH changes in man is not overwhelming. Gastrointestinal bleeding because of non-steroidal anti-inflammatory drugs is a major clinical problem, which we have investigated in a model system measuring bleeding rates caused by short-term administration of aspirin. Of the various strategies tested, only those that elevated intra-gastric pH reduced aspirin-induced bleeding.

Animals↗
PubMed1985

Double blind comparative study of omeprazole 10 mg and 30 mg daily for healing duodenal ulcers.

Healing of duodenal ulcers was assessed in 66 patients who received omeprazole either 10 mg or 30 mg daily for four weeks in a double blind study. Healing was rapid in both groups. At two weeks the ulcers in 15 of the 30 patients taking 10 mg daily had healed compared with 28 of the 36 (78%) taking 30 mg daily (p less than 0.03). At four weeks the respective proportions had risen to 83% (25/30) and 94% (33/35) (p greater than 0.05). In non-smokers the proportion of ulcers healed did not differ significantly with the two doses, although there was a trend for less healing at two weeks with 10 mg daily; in smokers significantly fewer ulcers (p less than 0.05) were healed with 10 mg than 30 mg daily at two weeks (7/16 (44%) v 17/21 (81%] and at four weeks (12/16 (75%) v all 21 (100%]. Adverse reactions were few and transient and were considered unlikely to be due to omeprazole.

Adult↗
PubMed1985

Omeprazole: a study of its inhibition of gastric pH and oral pharmacokinetics after morning or evening dosage.

Pharmacodynamic and pharmacokinetic studies of omeprazole, a new gastric antisecretory agent, were undertaken in 8 healthy subjects. The drug was administered orally as an encapsulated enteric-coated granulate (40 mg daily at 9 am or 9 pm for 5 days), and its effect on the integrated 24-h gastric pH was determined, together with its apparent bioavailability. The pretreatment 24-h median pH was 1.9 (interquartile range 1.4-2.9). After 5 days of treatment, the median pH had risen to 5.0 (3.7-6.0) (p less than 0.01) with morning dosage and 4.5 (3.0-5.6) (p less than 0.01) with evening dosage. This corresponded to a greater than 99% reduction in 24-h median hydrogen ion activity, with morning dosage having a greater effect (from 9 am to 8 pm) (p less than 0.01) than evening dosage. The relative bioavailability of omeprazole increased twofold from day 1 to day 5 of treatment with morning dosage (p less than 0.02) and threefold with evening dosage (p less than 0.02), suggesting that increased absorption of this acid-labile drug occurs with increasing inhibition of acid secretion. We conclude that this formulation of omeprazole presently being used in clinical trials is a highly potent antisecretory agent in humans, although its optimal effect may not be observed for several days.

Adult↗
PubMed1983

Simultaneous high-performance liquid chromatographic analysis of omeprazole and its sulphone and sulphide metabolites in human plasma and urine.

Omeprazole, a substituted benzimidazole which suppresses gastric acid secretion, and its sulphone and sulphide metabolites were simultaneously measured in human plasma and urine using a selective, reversed-phase, high-performance liquid chromatographic method with a sensitivity of 5 ng/ml for omeprazole, 30 ng/ml for omeprazole sulphone, and 50 ng/ml for omeprazole sulphide. The coefficients of variation for within-day assays were 4.4, 7.5, and 17.5%, respectively. In a pilot pharmacokinetic study, 40 mg of omeprazole (encapsulated enteric-coated granules) were administered to two healthy volunteers. Peak plasma concentrations for omeprazole of 240 and 520 ng/ml, and for omeprazole sulphone of 320 and 400 ng/ml, were reached between 3 and 4 h post-dose. Omeprazole concentrations fell rapidly with apparent half-lives of about 40 min, and concentrations of both omeprazole and the sulphone metabolite were below the minimal detectable level by 6-8 h. Omeprazole sulphide could not be detected in this study.

Adult↗
PubMed1980

Anaphylactoid reaction to 50% solution of dextrose.

Two patients with extrinsic asthma and coexistent insulin-dependent diabetes mellitus sustained an anaphylactoid reaction after the intravenous administration of 50% solution of dextrose. Investigations suggested that the dextrose, rather than any additives, was responsible for the reaction. The effect of varying concentrations of dextrose on the histamine content of the blood of normal, allergic, non-diabetic and diabetic, and non-allergic patients was studied. Preliminary results suggest that the higher concentrations of dextrose induce increased histamine release from blood cells, and that this phenomenon is more marked in diabetic, and particularly diabetic-allergic, individuals. We suggest that the treatment of hypoglycaemia with 50% solution of dextrose is associated with a significant risk factor in those diabetic individuals who are either allergic or are receiving beta-adrenoreceptor blocking drugs.

Aged↗