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Biomedical subjects

C J Hawkey

Publications and source records attributed to C J Hawkey.

At least 235 records · Page 13Linked to original sources
PubMed1987

Review: acute human models of gastric mucosal injury.

The use of acute human models of gastric mucosal injury has been stimulated by a need to understand more fully the problems of non-steroidal anti-inflammatory drugs but such models have other applications. None is ideal and they all share certain drawbacks. For none of them has a precise relationship to clinical events been established and they have all tended to be employed on a population of young healthy subjects who are not those at greatest clinical risk. Of individual methods mucosal potential difference is an indirect measure which is too often affected by other influences to be acceptable as a measure of mucosal injury when used alone, although it has some value as an adjunct to other measurements. Assay of DNA in gastric washings is a suitable technique for quantifying desquamation of gastric epithelial cells occurring in response to acute injury; on present evidence its significance is much more difficult to assess in the context of continuing challenge over several days. By contrast, measurement of microbleeding is more suitable for quantifying injury over several days of NSAID ingestion; little bleeding is recorded with a single acute challenge. Endoscopy can demonstrate macroscopic lesions which result from mucosal injury--injury which is quantified more easily and sensitively by measurements of cellular exfoliation or bleeding. Paradoxically, endoscopy's strength has been to underline the scientific weakness of acute models because it shows that it is rare for ulcers, which are the lesions of clinical concern to develop in these studies.

Animals↗
PubMed1987

Gastric mucosal protection with selective inhibition of thromboxane synthesis.

Because thromboxane synthesis enhances gastric mucosal damage we have investigated whether the thromboxane synthesis inhibitor dazmegrel might be protective to the mucosa. Dazmegrel at a dose of 1 and 5 mg per rat (4.8 and 23.8 mg/kg) significantly reduced the damage caused by acidified taurocholate. In parallel experiments dazmegrel exerted a selective and dose dependent inhibition of ex vivo thromboxane synthesis by gastric fragments over the dose range in which protection was observed. As dazmegrel can be given to man, these experiments suggest that investigation of mucosal protection would be justified.

Animals↗
PubMed1986

Prostaglandins for peptic ulcer: a promise unfulfilled.

Prostaglandin analogues appear to heal peptic ulcers no better than would be predicted from their ability to inhibit acid secretion. This implies that their cytoprotective properties, which are so dramatic in acute animal experiments, play no part in ulcer healing. Ulcer healing involves mucosal repair, whereas cytoprotection concerns preservation of normal mucosa, the two processes being conceptually different. If any general benefits of prostaglandin cytoprotection are to be harnessed to clinical ends, drug delivery systems that ensure long-lasting contact with the gastroduodenal mucosa may be needed.

Gastric Acid↗
PubMed1986

Reduction by enprostil of aspirin-induced blood loss from human gastric mucosa.

Enprostil's ability to protect human gastric mucosa against aspirin-induced damage was investigated in a controlled study. Damage was assessed as blood loss into gastric washings measured spectrophotometrically using orthotolidine in the presence of hydrogen peroxide. Phenol red was used to correct for recovery rates. Five doses of aspirin, 600 mg, given over 48 hours increased blood loss ninefold compared with placebo. Administration of enprostil 35 micrograms twenty minutes before each dose of aspirin halved this blood loss. After enprostil administration, the pH of both aspirated gastric juice and washings was significantly elevated, suggesting that an antisecretory dose had been used. Increased losses of phenol red occurred following both aspirin and enprostil administration, suggesting enhanced gastric emptying or possible absorption of phenol red as a result of aspirin damage. Side effects related mainly to the alimentary system were associated with enprostil treatment. Enprostil reduced aspirin-induced mucosal blood loss but the mechanism is unclear.

Adult↗
PubMed1986

Patterns of reactivity of the monoclonal antibody 791T/36 with different tumour metastases in the liver.

Reactivity of the monoclonal antibody 791T/36 with secondary malignant deposits has been investigated in frozen sections of 74 human liver biopsy specimens. There was no reactivity with hepatocytes but in some instances binding to fibrous tissues and in one case to portal tract lymphocytes was observed. Sections from 9 biopsy specimens contained malignant deposits. In seven of these 791T/36 bound either to malignant cells or to pseudoacinar contents (3 colorectal adenocarcinomas; 1 probable pancreatic adenocarcinoma; 1 medullary cell carcinoma of thyroid; 1 oat cell carcinoma of bronchus and 1 deposit of nodular sclerosing Hodgkins Disease). Two undifferentiated tumours (1 gastric adenocarcinoma and 1 oat cell bronchial carcinoma) showed no antibody binding. The histological pattern of reactivity previously reported with primary tumours appears to be similar in secondary deposits. A wider range of tumours than recognised hitherto binds 791T/36. Whether the binding to fibrous tissue seen in some instances is sufficient to cause diagnostic uncertainty when 791T/36 is used for scanning requires further investigation.

Adenocarcinoma↗
PubMed1986

Proposed pathogenic mechanism for the diarrhea associated with human intestinal spirochetes.

Spirochetes resembling Brachyspira aalborgi were found in the feces and rectal biopsies of a patient with persistent diarrhea. Although the organism failed to grow on bacteriologic media, it was found attached to the surfaces of the epithelial cells on the rectal lumen. Blunting and destruction of the cellular microvilli was evident. These induced pathologic cell surface changes, together with the presence of intracellular bacteria in the cells of the rectal colon, suggest a pathogenic mechanism for the persistent diarrhea often associated with this condition. Both the spirochetosis and clinical symptoms disappeared on treatment with metronidazole.

Adolescent↗
PubMed1986

Synthesis of prostaglandin E2, thromboxane B2 and prostaglandin catabolism in gastritis and gastric ulcer.

Because endogenous prostaglandins may protect the gastric mucosa a study was conducted to determine factors influencing the synthesis of immunoreactive prostaglandin (iPG) E2 and thromboxane (iTx) B2 as measured by radioimmunoassay and prostaglandin catabolism measured radiometrically, in human gastric mucosa. Gastric mucosa was obtained at endoscopy. Synthesis of iPE2 and iTxB2 was inhibited in vitro by indomethacin; iTxB2 synthesis was also selectively inhibited by the thromboxane synthesis inhibitor dazmegrel. Prostaglandin catabolism was inhibited by carbenoxolone. Multivariate analysis showed that synthesis of iPGE2 from endogenous precursor during homogenisation was decreased in patients on non-steroidal anti-inflammatory drugs. Mucosal inflammation was associated with significantly increased synthesis of iPGE2 and decreased prostaglandin catabolism. There were no differences between the mucosa of patients with or without gastric ulcers, nor between the ulcer rim and mucosa 5 cm away. Age, sex, smoking history and ingestion of antisecretory drugs appeared to exert no influence. In this study gastritis was the major influence on prostaglandin synthesis. It seems unlikely that prostaglandin deficiency is a strong predisposing factor for gastric ulceration.

Dinoprostone↗
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↗
PubMed1986

Haemorrhage from idiopathic annular ulcers of the small intestine.

Annular small bowel ulceration is rare. We report three patients who presented with signs of chronic gastrointestinal blood loss. In two patients the main presenting symptom was intermittent abdominal pain while the third patient subsequently developed abdominal pain during the course of investigation. Preoperative localisation of the source of haemorrhage proved difficult in each case. However in all three patients an easily identifiable lesion was found at laparotomy. We believe that laparotomy should be undertaken more readily in the investigation of patients with the combination of abdominal pain and gastrointestinal bleeding as these patients are likely to have an anatomically identifiable cause for their symptoms.

Abdomen↗
PubMed1985

Somatostatin in treatment of haematemesis and melaena.

630 patients with haematemesis and melaena were randomly allocated to treatment by a constant intravenous infusion of either somatostatin or an apparently identical placebo in a double-blind controlled trial. Rebleeding was less common in treated patients (70 episodes in 315 individuals compared with 89 episodes in 315 controls) but the difference was not significant. Operation rates were virtually identical (35 treated patients and 34 controls), while there were slightly more deaths in the treated group than in the controls (31 and 25, respectively). These results are in clear disagreement with those of other smaller series. Though it is not possible to be completely sure that treatment is not useful in some individuals, earlier claims of marked benefit seem unlikely to be justified.

Clinical Trials as Topic↗
PubMed1985

Modulation of human colonic arachidonic acid metabolism by sulfasalazine.

The effects of sulfasalazine and its moieties on synthesis of individual products of arachidonic acid metabolism by human colonic mucosa have been investigated. Sulfasalazine inhibited synthesis of the lipoxygenase products. Sulfasalazine and sulfapyridine also inhibited synthesis of thromboxane B2 while enhancing synthesis of prostaglandin (PG) F2 alpha or PGE2, respectively. Inhibition of synthesis of lipoxygenase products and modulation of the profile of cyclooxygenase products could reduce inflammation and enhance mucosal resistance to damage in ulcerative colitis.

Aminosalicylic Acids↗
PubMed1985

Prostaglandins and the gastrointestinal mucosa: are they important in its function, disease, or treatment?

In 1971 interest in the role of prostaglandins in the gastrointestinal tract was stimulated by the publication of two hypotheses--that aspirin damaged the gastric mucosa by inhibiting prostaglandin synthesis (1) and that cholera toxin caused diarrhea by stimulating it (2). Subsequent research into the gastrointestinal actions of prostaglandins has been considerable and now impinges on clinical practice. This paper reviews the involvement of prostaglandins and related compounds in mucosal protection, in ulcer healing, in diarrhea, and in gastrointestinal inflammation, with particular reference to the growing body of human data.

Animals↗
PubMed1985

In-vitro enhancement of cholesterol dissolution by commonly used drugs.

A rotating disc apparatus was used to study the dissolution of cholesterol in sodium cholate solutions and ox bile. Drugs with structures that render them capable of lowering interfacial resistance were tested and shown to increase cholesterol dissolution rates in both systems. In sodium cholate solutions, loperamide (3 X 10(-4)M) increased the rate of dissolution by over six times, and a similar effect was observed with amitriptyline (3 X 10(-3)M), diphenhydramine (3 X 10(-3)M), dicyclomine (3 X 10(-3)M) and propantheline (3 X 10(-3)M). These drugs are as effective as benzalkonium chloride at these concentrations. Amitriptyline, propantheline, dicyclomine and diphenhydramine also increased cholesterol dissolution rates into ox bile. If these drugs are excreted into human bile in sufficient quantities and in an active form they may be able to enhance the speed of cholesterol gallstone dissolution therapy.

Animals↗
PubMed1985

Intravenous omeprazole rapidly raises intragastric pH.

Twenty four hour intragastric acidity was measured in five duodenal ulcer patients studied at least three times. The effects of different dosage regimens of intravenous omeprazole was compared with placebo. Mean intragastric acidity from 1000 to 0800 was 34.3 +/- 4.3 mmol/l on placebo. After omeprazole 80 mg at 0900 and 40 mg at 1700 mean acidity was 2.1 +/- 0.9 mmol/l and after omeprazole 80 mg at 0900 and 80 mg at 1700 it was 0.7 +/- 0.2 mmol/l. pH remained above 4.0 for about 80% of recordings with these regimens and for only 5% with placebo. Three of the five patients also received omeprazole 80 mg at 0900, 40 mg at 1700 and 40 mg at 0100 when pH remained above 4.0 for 90% of recordings with 99% inhibition of acidity. Omeprazole rapidly raised intragastric pH in all patients and maintained a gastric pH of greater than 4.0 for most of the time. Large doses of IV omeprazole were required compared with studies using the oral compound.

Adult↗
PubMed1985

Pleomorphic T-cell leukaemia in a Caucasian adult: clinical phenotypic and functional characteristics.

Pleomorphic T-cell leukaemia occurring in an adult Caucasian patient is described. The leukaemia cells expressed both antigenic determinants (T4 and T8) normally detected separately on either helper or suppressor cells. They functioned as helper cells and there was evidence of unbridled antibody production. It is possible that a distinctive subtype of pleomorphic T-cell leukaemia occurs in Caucasian patients.

Epitopes↗