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Biomedical subjects

C J Hawkey

Publications and source records attributed to C J Hawkey.

At least 253 records · Page 14Linked to original sources
PubMed1984

Comparison of the Eder-Puestow and Celestin techniques for dilating benign oesophageal strictures.

The Celestin and Eder-Puestow methods of dilating benign oesophageal strictures have been compared prospectively in a randomised trial. One hundred and thirty three dilatations were performed on 72 patients. There was no significant difference between the two techniques with regard to the long term relief of symptoms. Celestin dilatation was quicker, less likely to cause pharyngeal trauma, and less damaging to guide wires. It could not be used, however, in those patients in whom only a short length of guide wire could be passed through the stricture.

Deglutition Disorders↗
PubMed1983

Haemostatic changes following surgery.

Changes in factors V, VII and VIII and in fibrinogen were studied in 32 patients undergoing major abdominal surgery. Mean levels of factors V and VII were similar to population-based values preoperatively. Factor V fell following elective surgery and then rose above the mean pre-operative level before returning to it by the tenth post-operative day. Factor VII fell following both elective and emergency surgery and tended to remain depressed throughout the post-operative period. Pre-operative values of factor VIII and fibrinogen were higher than population-based values and higher in the emergency than in waiting-list patients. Both factor VIII and fibrinogen rose following elective surgery but no statistically significant change was seen following emergency surgery. The uncomplicated conditions leading to elective surgery, the acute complications leading to emergency surgery, and surgery itself may each have contributed to increases in factor VIII and fibrinogen levels, whereas the fall in factors V and VII was largely related to surgery itself. The findings may help in the interpretation of associations between clotting factors and thrombotic disease, particularly in the case of factor VII.

Aged↗
PubMed1983

Benoxaprofen in the treatment of active ulcerative colitis.

We have conducted an open pilot trial to assess the therapeutic effect of the lipoxygenase inhibitor, benoxaprofen, in 10 patients with active ulcerative proctocolitis. After 18 days treatment with benoxaprofen (600 mg daily) there was no significant change in bowel habit, rectal bleeding, constitutional upset, sigmoidoscopic appearance, mucosal histology, haemoglobin, ESR, serum albumin or serum orosomucoid. Benoxaprofen itself seems unlikely to prove useful in ulcerative colitis, but evaluation of the therapeutic potential of other lipoxygenase inhibitors in inflammatory bowel disease may be worthwhile.

Adolescent↗
PubMed1983

A thromboxane synthetase inhibitor in Raynaud's phenomenon.

The balance between thromboxane A2 (a vasoconstrictor) and prostacyclin (a vasodilator) may be important in the pathogenesis of Raynaud's phenomenon. Dazoxiben is a selective inhibitor of thromboxane synthetase, with no effect on prostacyclin synthetase. It has been shown to abolish cold induced forearm vasoconstriction in normal volunteers. We have compared its effect with that of placebo in a double blind crossover study in eight patients with severe Raynaud's phenomenon. No consistently clinically useful benefit was demonstrated from three weeks' treatment with dazoxiben, and there were no significant changes in finger temperature or finger blood flow. We conclude that dazoxiben at this dosage is unlikely to be of practical clinical benefit in Raynaud's phenomenon.

Adult↗
PubMed1983

A monoclonal antibody reactive with human hepatocytes.

A monoclonal antibody, RL23/36, reacting preferentially with a determinant expressed on normal human hepatocytes is described. Use of an immunohistochemical technique on frozen sections from a range of 75 human liver biopsy specimens revealed that the determinant detected by RL23/36 was not expressed on hepatocytes from a number of patients with biopsy-proven liver disease. Although a normal staining pattern was observed in 28 of 29 biopsy specimens from patients with no evidence of liver disease, the antibody did not bind to hepatocytes in some cases of chronic active hepatitis (2/13), alcoholic liver disease (2/9), haemochromatosis (1/1), cirrhosis (1/2) and liver metastases (2/8). Furthermore, as in a previous study undertaken in the rat, the antibody failed to bind to tumour cells in the single human hepatoma observed in this study. These results suggest that further studies using RL23/36 may shed light on the pathogenesis of a number of liver diseases, including primary hepatocellular carcinoma.

Animals↗
PubMed1983

Imbalance of prostacyclin and thromboxane synthesis in Crohn's disease.

Synthesis of prostanoids in Crohn's disease was investigated using rectal biopsy specimens maintained in organ culture. As with ulcerative colitis increased synthesis of prostaglandin (PG)E2 was observed when the mucosa was inflamed, compared with uninflamed mucosa in Crohn's disease, and with control biopsy specimens. In contrast with ulcerative colitis differences from control specimens were observed even in the absence of inflammation. There was a raised synthesis of thromboxane (Tx)B2 (stable breakdown product of TxA2); concentrations of 6-keto PGF1 alpha (stable breakdown product of prostacyclin) were unchanged and hence the ratio of 6-keto PGF1 alpha/TxB2 was reduced. These changes might lead to an altered cytoprotective capacity or reduced suppressor cell activity, such as has previously been reported in intestinal lymphocytes in Crohn's disease.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Biosynthesis of lipoxygenase and cyclo-oxygenase products from [14C]-arachidonic acid by human colonic mucosa.

The human colon synthetises several prostanoids which may have a role in inflammatory bowel diseases. As lipoxygenase products of arachidonate metabolism have been implicated in inflammatory processes, we have now investigated the formation of both lipoxygenase and cyclo-oxygenase metabolites from [14C]-arachidonic acid [(14C]-AA) by human colonic tissue. Homogenates of human colonic mucosa were incubated with [14C]-AA and after extraction into diethyl ether, separated by thin layer chromatography using two solvent systems that allowed resolution of cyclo-oxygenase and lipoxygenase products. The predominant cyclo-oxygenase products, as identified by their chromatographic mobility, were PGE2 greater than PGF2 alpha greater than PGD2 greater than TXB2 greater than 6-keto-PGF1 alpha. The formation of these products was inhibited both by indomethacin (1-10 microM) and the dual pathway inhibitor, BW755C (1-30 microM). The predominant lipoxygenase products formed, which had the chromatographic mobility of 11-, 12-, 15-HETE (which ran together) were inhibited by BW755C (19 microM) but not by indomethacin (3 microM). Further resolution of this TLC band, performed using normal phase HPLC, indicated that both 12-HETE and 15-HETE were major lipoxygenase products formed by human colonic homogenate. The present findings indicate that human colonic tissue can convert [14C]-AA into lipoxygenase as well as cyclo-oxygenase products and support the suggestion that lipoxygenase products may have a role in inflammatory bowel disease.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1983

Inhibition of prostaglandin synthetase in human rectal mucosa.

Miniaturised methods have been used to construct dose-response curves for the effects of inhibitory drugs on prostaglandin synthesis using individual rectal biopsies obtained from patients with ulcerative colitis. The potency of different drugs has been compared. Sulphasalazine, 5 amino salicylic acid (5-ASA) and N-acetyl 5-ASA inhibited prostaglandin synthesis at high concentration, but sulphapyridine and prednisolone did not. Indomethacin and flurbiprofen were considerably more potent inhibitors. These data imply that sulphasalazine does not act by simple inhibition of prostaglandin synthesis but leave open the possibility that sulphasalazine or 5-ASA may be inhibitors of the synthesis of related lipoxygenase products.

Aminosalicylic Acids↗
PubMed1983

The need for prophylactic treatment to the central nervous system in patients with aggressive non-Hodgkin's lymphoma.

During 2 years, 6 out of 34 patients presenting with newly diagnosed non-Hodgkin's lymphoma developed central nervous system (CNS) complications. All were male and had diffuse, undifferentiated lymphomas. In all 6 patients, CNS disease developed during, or shortly after, treatment. We suggest that a group at high risk from these complications can be identified and should be considered for a trial of prophylaxis.

Adult↗
PubMed1981

Effect of prednisolone on prostaglandin synthesis by rectal mucosa in ulcerative colitis: investigation by laminar flow bioassay and radioimmunoassay.

The effect of two concentrations of prednisolone on synthesis of prostaglandin E2 (PGE2) by 40 rectal biopsies in organ culture was investigated using both laminar flow bioassay and radioimmunoassay (RIA). Prednisolone (concentration 8.33 x 10(-7)M) reduced mean synthesis of PGE2 to 36.4% of control values (measured by bioassay) or 26.2% of control values (measured by RIA). With prednisolone (concentration 5.66 X 10(-4) M) synthesis of PGE2 was 7.7% of control values (RIA). The two concentrations are similar respectively to those achieved in plasma after oral prednisolone and delivered topically by prednisolone enemata. Inhibition of PG synthesis may thus explain prednisolone's anti-inflammatory action in the treatment of ulcerative colitis.

Biological Assay↗
PubMed1981

Plasma exchange and immunosuppressive drug treatment in myasthenia gravis: no evidence for synergy.

We have investigated whether plasma exchange in myasthenia gravis synergises with additional immunosuppressive drug therapy (azathioprine, cyclophosphamide or cytosine arabinoside). Serum anti-acetylcholine receptor (AChR) antibody titres were followed over 28 days after a course of PE in 20 patients, of whom 17 were taking 20-80 mg prednisone on alternate days. No significant difference was observed in mean anti-AChR antibody recovery following plasma exchange with and without additional immunosuppressive therapy. In paired studies where patients served as their own controls, mean anti-AChR recovery with and without azathioprine or cytosine arabinoside showed no significant differences. Anti-AChR recovery rates after large and small plasma exchange courses also did not differ significantly. Prolonged administration of azathioprine reduced antibody titres independently of plasma exchange. These results fail to demonstrate significant synergy between plasma exchange and the additional immunosuppressive drugs used, and suggest that the effects of plasma exchange were transient.

Adolescent↗
PubMed1976

The Prader-Willi syndrome with a 15/15 translocation. Case report and review of the literature.

A case, diagnosed clinically as the Prader-Willi syndrome, was shown by Giemsa banding, to have a 15/15 chromosome translocation. A review of the literature indicates that such a translocation has only been described once before, in a normal woman, but that chromosme abnormalities in the Prader-Willi syndrome most commonly involve the D group. The significance of this would be clarified by specific chromosome identification in these patients.

Adult↗