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Biomedical subjects

D A Robertson

Publications and source records attributed to D A Robertson.

At least 73 records · Page 4Linked to original sources

H2 antagonists in the treatment of reflux oesophagitis: can physiological studies predict the response?

Ambulatory oesophageal pH, oesophageal manometry and fasting serum gastrin concentrations were carried out on 28 patients with reflux oesophagitis, before and during treatment with ranitidine 300 mg bd. Fourteen patients healed endoscopically at six weeks (group A) and 14 had residual oesophagitis (group B). Group A were characterised by a lower serum gastrin concentration before treatment (4.52 pmol/l; 2.4-10: mean and range) than group B (11.1 pmol/l; 3.5-21: p less than 0.05) and showed a marked reduction in acid reflux on treatment to near normal values. Mean per cent time below pH4 fell from 14.9 to 4.2 in group A (p less than 0.05) but was not affected in group B (14.2-15.6, not significant). Abnormal oesophageal motility was found in 13 patients from each group. This did not inhibit the response to ranitidine, and was not improved by healing of oesophagitis.

Adolescent↗

Negative inotropic effect of platelet-activating factor on human myocardium: a pharmacological study.

Because platelet-activating factor (PAF) has prominent depressant effects on cardiac contractility in various mammalian species, we assessed the negative inotropic effect of PAF on non-coronary perfused human right atrial pectinate muscles paced at constant rate. We found that PAF is a potent negative inotropic agent (EC50 approximately equal to 160 pM), whose action is unmodified by atropine, indomethacin and the leukotriene receptor antagonist compound FPL 55712. The negative inotropic effect of PAF was, however, antagonized by drugs known to inhibit PAF-induced platelet aggregation: the order of relative potency was SRI 63-441 greater than CV-3988 greater than alprazolam greater than or equal to triazolam; i.e., the same order in which these compounds antagonize the effects of PAF on platelets. Thus, the potent negative inotropic effect of PAF on human myocardium is independent of coronary flow changes, involves neither cholinergic mechanisms nor arachidonate metabolites and is probably mediated by specific receptors.

Calcium↗

IgE-mediated hypersensitivity in human heart tissue: histamine release and functional changes.

In experiments described herein, it was observed that IgE-mediated hypersensitivity can result in significant histamine and thromboxane release from human myocardium, suggesting that the human heart may participate as a target organ in allergic reactions. Muscle units (pectinate muscles) were isolated from human atrial appendages, removed routinely during corrective cardiac surgery, and were allowed to beat spontaneously in a tissue bath. Remnants of each atrial specimen were chopped and added to the tissue bath. Challenge of the atrial tissue with goat antiserum to human myeloma IgE caused histamine and thromboxane B2 release and marked increases in contractility and spontaneous rate. In contrast, challenge with nonspecific goat antiserum or with antiserum from which anti-IgE antibodies had been removed caused neither mediator release nor changes in rate or contractility. The histamine H2-receptor antagonist cimetidine inhibited the inotropic and chronotropic changes but not the histamine release.

Adult↗

Leucocyte migration inhibition test in coeliac disease - a reappraisal.

Results of the direct leucocyte migration inhibition (LMI) test using gluten fraction III as antigen were unaffected by incorporation of puromycin into the culture medium at concentrations shown to prevent lymphokine mediated inhibition. Results of the LMI test performed with purified polymorphs were similar to and correlated with results of the standard LMI test using mixed leucocytes in both coeliacs and controls. The addition of purified T lymphocytes did not increase migration inhibition. Normal leucocytes incubated with serum from coeliac patients and washed showed marked migration inhibition when incubated with gluten fraction III. This sensitisation of normal leucocytes was prevented by preincubation with aggregated human IgG. These results suggest that leucocyte migration inhibition by gluten in coeliac disease is not due to lymphokine production by sensitised lymphocytes but is caused by cytophilic antibody.

Adolescent↗

Small intestinal ulceration: diagnostic difficulties in relation to coeliac disease.

Seven cases of ulceration of the small intestine are described and the relationship to coeliac disease is discussed. Evidence for coeliac disease is found in all cases but is less strong in some than in others, and coeliac disease was proved in only two cases. The ulcers were examined histologically in each case and in three cases were associated with malignant histiocytosis but the others showed only non-specific chronic inflammation. This suggests a spectrum of disorders with an inconsistent relationship to gluten sensitivity and small intestinal lymphoma.

Adult↗

Effects of intrauterine infusion of oestradiol-17 beta and prostaglandin E-2 on luteal function in non-pregnant heifers.

Non-pregnant heifers (4/group) received intrauterine infusions of vehicle, oestradiol-17 beta (150 ng), PGE-2 (250 micrograms), or oestradiol + PGE-2 every 6 h from 12:00 h on Day 13 to 06:00 h on the day of subsequent oestrus or 06:00 h on Day 21 (day of oestrus = Day 0). Ten of 12 heifers receiving vehicle, oestradiol or PGE-2 returned to oestrus by Day 21, whereas none of the heifers receiving oestradiol + PGE-2 returned to oestrus by Day 21. Jugular venous progesterone concentrations of vehicle- and PGE-2-treated heifers declined rapidly after Day 15 and were basal (less than 1 ng/ml) by Day 20. For heifers receiving oestradiol infusions, systemic progesterone levels did not decline until after Day 18, but were again basal by Day 20. Heifers treated with oestradiol + PGE-2 maintained elevated systemic progesterone levels until Day 21 after oestrus. In addition, the corpora lutea of the heifers treated with oestradiol + PGE-2 were heavier (P less than 0.01) and contained more (P less than 0.05) progesterone than did corpora lutea of the heifers in the other 3 groups on Day 21 (3.4 g and 19.52 micrograms/g and 1.2 g and 1.65 micrograms/g, respectively). It is concluded that oestradiol-17 beta and PGE-2, both of which are produced by the bovine conceptus and secreted from the gravid uterus, may act synergistically to maintain luteal function during early pregnancy in the cow.

Animals↗

Jejunal biopsy and lymphocyte co-culture in coeliac disease.

Jejunal biopsies from 13 patients with treated coeliac disease were maintained in organ culture for 24 h with and without the addition of gluten fraction III, in each case with and without autologous peripheral blood mononuclear cells. Biopsies cultured with gluten alone or with lymphocytes alone showed no significant reduction in mean enterocyte height compared with those cultured in control medium, but those cultured with both gluten and lymphocytes had significantly lower enterocyte height than control biopsies, than those cultured with gluten alone, and than those cultured with lymphocytes alone. These results demonstrate that the combination of gluten and lymphocytes is more toxic to treated coeliac mucosa in vitro than either one alone and support the suggestion that immune reactions to gluten may be important in the pathogenesis of the mucosal lesion of coeliac disease.

Adult↗

Splenectomy causes auto-antibody formation.

Serum from 45 splenectomised patients was screened for 8 auto antibodies and compared with controls, either age and sex matched (35) or the same patients measured before splenectomy (10). Sixteen splenectomised patients had demonstrable auto-antibodies compared with 7 controls (p less than 0.05). Three patients who did not have auto-antibodies before splenectomy developed them after an interval of a few months. It is suggested that splenectomy-leads to loss of suppressor cell activity and this permits the development of auto-antibodies.

Adolescent↗

Duodeno-gastric reflux in normal and dyspeptic subjects.

A simple radiological technique is described for detecting the presence, or absence, of duodeno-gastric reflux (DGR) at barium meal examination. The incidence of DGR was found to be approximately the same in both normal volunteers and dyspeptic patients. Although there was a slight trend towards an increased incidence in gastric ulcer, this did not reach statistical significance. The severity of reflux did not correlate with the presence of peptic ulceration. DGR appears to be more common with increasing age. Our results cast doubt on the hypothesis that reflux of duodenal content plays a primary role in the pathogenesis of gastric ulcer.

Adolescent↗

Coeliac disease, splenic function, and malignancy.

Blood films from 41 cases of coeliac disease complicated by malignancy were examined and evidence of hyposplenism found in 12 cases (29%). This is similar to the proportion of adult coeliacs without malignancy who have hypoplenism and it is concluded that impaired splenic function is not associated with the development of malignancy in coeliac disease.

Adult↗

Cell-mediated immunity to dietary antigens in coeliac disease.

By means of the leukocyte migration inhibition test a significant depression of migration index (indicating increased immunity) was found in 10 untreated coeliac patients compared with 24 control subjects with the dietary antigens bovine serum albumin (BSA) and egg white but not with milk. The degree of immunity was similar to that obtained with gluten fraction III as antigen. Treatment with a gluten-free diet led to a decrease in immunity to egg white and BSA, but immunity to gluten fraction III was increased in the early months of treatment.

Adolescent↗

Suppressor cell activity, splenic function and HLA B8 status in man.

The enhanced proliferative response of peripheral blood lymphocytes (P.B.L.) to Concanavalin A (Con A) occurring after a 24 hr period of incubation was used as the basis of a suppressor cell assay and the results expressed as a suppressor index (S.I.) which if low implies impaired suppressor cell activity. S.I. was measured on P.B.L. from 26 patients with coeliac disease and defined splenic function, 8 patients with splenic atrophy not associated with coeliac disease, 30 patients after surgical splenectomy, and 52 controls. S.I. was lower than control in the splenectomy group (P less than 0.01) and in the coeliac group, but coeliacs with splenic atrophy were no different from coeliacs with apparently normal splenic function, nor were the non-coeliac splenic atrophy group different from control. Coeliacs with the HLA B8 gene had lower S.I. than those without, as did controls. Suspensions of cells from spleens removed at laparotomy demonstrated suppressor activity but this was no more marked than in P.B.L. It is concluded that the intact spleen is required for normal activation of suppressor cells in man, but this function is retained in splenic atrophy, and that the HLA B8 gene is associated with low suppressor cell activity in coeliac disease and in health.

Celiac Disease↗