Biomedical subjects
Publications and source records attributed to R D Stevenson.
In two patients who had recently undergone major abdominal operations and were later suspected of having pulmonary emboli, pulmonary angiography showed no evidence of embolism, but in both cases one of the hemidiaphragms was clearly outlined by contrast material. It is suggested that subdiaphragmatic inflammation was responsible for this unusual appearance.
Theophylline stimulates the capillary tube migration of human peripheral blood mixed leucocytes. Minor stimulation of polymorph migration is produced directly by theophylline and dibutyryl cyclic AMP, but polymorph migration is markedly stimulated by mononuclear leucocyte culture supernatants to which theophylline has been added. These results suggest that polymorph migration is stimulated when intracellular cyclic AMP increases, and that mononuclear leucocytes produce a potential migration stimulator whose activity is enhanced by theophylline.
A male infant presented with dermatitis, purpura and susceptibility to bacterial infections. The clinical diagnosis of Wiskott-Aldrich syndrome was confirmed and after full immunological assessment, treatment with transfer factor was commenced. This has resulted in a rise in the platelet count and improvement in the bleeding tendency. This improvement in the haematological aspect of the disease has, however, been accompanied by exacerbations of the cutaneous lesions.
Polymorph migration stimulator (PMS) is a peptide factor produced by an in vitro reaction between glucocorticoids and human mononuclear phagocytes. This study was undertaken to determine the significance of the stimulatory effect of PMS on the capillary tube migration of human polymorphs. Colchicine, vinblastine and Nocodazole, all of which inhibit microtubular assembly, are shown to stimulate migration. Conversely, deuterium oxide which stabilizes microtubules inhibits migration. Increased intracellular cyclic AMP is associated with microtubular inhibition and isoprenaline, theophylline and dibutyryl cyclic AMP are also found to stimulate capillary tube migration. These results suggest that PMS acts by inhibiting the assembly of polymorph microtubules, an effect which may be mediated by cyclic AMP in the same manner as other peptide hormones.
The addition of prednisolone to autostimulatory cultures of human bone marrow in agar results in the formation of an increased number of granulocytic aggregates. The effect is dependent on the concentration of cultured cells and does not occur at low cell concentration. The increase in aggregate numbers is maximal early in the culture and occurs at steroid concentrations which are comparable with pharmacological levels. Prednisolone directly inhibits the responsiveness of granulocytic precursors to colony-stimulating activity (CSA) and it is suggested that the stimulatory effect is indirect and may be caused by a steroid action on mediator production. These findings may be relevant to the polymorphonuclear leucocytosis induced by glucocorticoids.
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Glucocorticosteroids react with blood monocytes and tissue macrophages to produce a peptide factor which stimulates the random migration of polymorphs in vitro in the capillary-tube migration system. An identical effect on polymorph migration is produced by colchicine and vinblastine, drugs which inhibit the assembly of the cytoplasmic microtubules on which the functional activity of polymorphs depends. Pharmacological agents which inhibit microtubular assembly indirectly by increasing intracellular cyclic adenosine monophosphate (A.M.P.), also stimulate polymorph migration in vitro. These observations suggest that the anti-inflammatory activity of glucocorticosteroid drugs is mediated by a peptide hormone which inhibits polymorph microtubular assembly. Many peptide hormones are believed to act by increasing the concentration of cyclic A.M.P. within target cells and this mechanism is probably also responsible for the inhibitory effect of steroids on phagocytic cells.
Although five patients with severe pre-eclamptic toxaemia (PET) had increased anticomplementary activity in their serum, there was no evidence of complement activation in the plasma of four of the five patients. These results are not implicated in the pathogenesis of PET. No significant correlation was found between anticomplementary activity and pregnancy-associated alpha2-glycoprotein.
This paper describes an in vivo method for measuring total thyroidal iodine stores by activation analysis, its evaluation and measurements in thyrotoxic patients. There was good correlation between measurements of solutions of iodine and post-mortem thyroids by activation analysis and chemical analysis. Measurements in thyrotoxic patients showed low levels in untreated and treated (antithyroid drugs) patients and a marked increase in patients studied whilst in clinical remission. The practical importance of this method of measurement of thyroidal iodine stores is that it is a reliable in vivo measurement obtained at a single visit and should enable the definition of the relationship of thyroidal iodine stores to pathophysiology and prognosis.
Polymorph migration stimulator is a supernatant factor produced by the interaction between glucocorticosteroids and human blood monocytes in culture. Studies on the physical characteristics of this factor show that it is soluble and stable at high and low temperatures. Its activity is reduced by acid and alkali treatment and destroyed by the proteolytic enzyme protease. Experiments involving dialysis, ultrafiltration and Sephadex G-100 gell filtration indicate that the molecular weight of the polymorph migration stimulator is between 12,000 and 15,000. It is suggested that this factor may mediate the anti-inflammatory effects of glucocorticosteroids on phagocytic cells.
Human blood monocytes are known to react with hydrocortisone in vitro to produce a factor which stimulates polymorph migration. This study shows that the polymorph migration stimulator (PMS) is generated only by steroids with glucocorticoid activity. The interaction between steroid and monocytes is dependent on protein synthesis. Serum is necessary for the expression of the activity of the factor, but the steroid-monocyte reaction can occur in the absence of serum. The stimulatory effect on migration appears to be specific for polymorphs and does not affect mono-nuclear leucocytes. In addition to blood monocytes, spleen and bone marrow cells also react with corticosteroids to produce the polymorph migration stimulator.
Eight cases of septic arthritis occurring in patients with rheumatoid arthritis are reviewed. The difficulty in diagnosis of this condition is due in part to a failure of these patients to respond normally to infection. Consequently patients often present late in the course of their septic episode and treatment is often delayed. The importance of early diagnosis and treatment of the infection is stressed by the high mortality rate in this group of patients. Many factors operate to encourage infection in rheumatoid arthritis and the current concepts of the problem are reviewed.
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