Biomedical subjects
M L Barrett
Publications and source records attributed to M L Barrett.
Diagnosing childhood depression who should be interviewed--parent or child? The Newcastle Child Depression Project.
The extent of the similarities and discrepancies in the reporting of depressive symptomatology by children and their mothers was examined. Child-parent agreement was not always impressive, particularly for more subjective symptoms. It is suggested that direct psychiatric assessment of children provides a more accurate picture of their mental state regardless of presenting disorder, but particularly where depression is suspected.
The context of childhood depression. The Newcastle Childhood Depression Project.
This paper examines the family background, premorbid personality traits and adverse life events preceding childhood depression. The non-depressed group proved more likely to have experienced pre-school bereavement and familial disturbance, and to come from the more deprived background; there was also an excess of premorbid anxiety and hysterical personality traits in this group. School phobia and premorbid obsessional traits were associated with the depressed group. Although there was an association between depression and the total number of adverse life events, this was more substantial when the perceived impact of the events was taken into account. Of the individual classes of life event, only illness and a change in social relationships were associated specifically with depression.
The dexamethasone suppression test in children: lack of an association with diagnosis.
The dexamethasone suppression test was carried out on 44 children to assess agreement with diagnosis of depression. No significant association was found between suppression of plasma cortisol and depression diagnosed clinically or by cluster analysis.
The Newcastle Child Depression Project. Diagnosis and classification of depression.
A total of 275 successive referrals to a university child psychiatry unit out-patient department were examined using the Child Depression Inventory. Of these, 95 children were examined further by a structured clinical interview, and the relationship between different instruments for the assessment of depression in childhood was investigated. Just over one-third of the children (35%) had significant depression, and it was found that depression may be missed unless children with other psychiatric diagnoses are examined closely. Multivariate analyses of the clinical data provided factorial validation of diagnoses when employing different clinical diagnostic schemas.
Inhibition of platelet-derived mitogen release by nitric oxide (EDRF).
Platelets exposed to thrombogenic surfaces adhere, aggregate and release mitogenic substances from their alpha-granules. Endothelium-derived relaxing factor (EDRF) which has been identified as nitric oxide (NO) has been reported to inhibit platelet aggregation. We now report that NO inhibits mitogen release from stimulated human platelets. Mitogenic activity was assayed on mouse fibroblast 3T3 cells using incorporation of 3H-thymidine. Serum from collagen-aggregated platelets significantly increased 3H-thymidine incorporation by 3T3 cells above that of serum from control platelets. Both this increase and platelet aggregation were blocked by NO and prostacyclin in a dose related manner. The inhibitory activity of NO decayed with time when incubated in platelet-free plasma at 37 degrees C, but was still detectable after 2 minutes.
Induction of cyclo-oxygenase by interleukin-1 in rheumatoid synovial cells.
The ability of interleukin-1 (IL-1) to stimulate prostaglandin E2 (PGE2) production by human rheumatoid adherent synovial cells was found to be time-dependent and sensitive to protein synthesis inhibitors. Cells incubated with exogenous arachidonic acid (10 microM) showed no increase in PGE2 production. However, with IL-1 (2.5 U/ml) and exogenous arachidonic acid there was a marked increase, with levels reaching twice that for cells incubated with IL-1 alone. Aspirin pre-treatment studies and the use of [acetyl-14C]aspirin showed that IL-1 increased PGE2 production through the induction of cyclo-oxygenase.
Extracts of feverfew inhibit mitogen-induced human peripheral blood mononuclear cell proliferation and cytokine mediated responses: a cytotoxic effect.
Feverfew has been used since antiquity to treat inflammatory conditions. Extracts of the herb were found to inhibit mitogen-induced tritiated thymidine ([3H]-TdR) uptake by human peripheral blood mononuclear cells (PBMC), interleukin 2 (IL-2)-induced [3H]-TdR uptake by lymphoblasts and PGE2 release by interleukin 1 (IL-1)-stimulated synovial cells. Parthenolide, a major secondary metabolite from the herb also blocked [3H]-TdR uptake by mitogen-induced PBMC. However, both crude extracts and parthenolide proved cytotoxic to mitogen-induced PBMC and IL-1 stimulated synovial cells, the cytotoxic effect being functionally indistinguishable from the inhibitory effects. The pharmacological properties of feverfew may thus be due to cytotoxicity, although the time course of the events described in this paper is different from those where feverfew appears to have more specific inhibitory effects.
Cannflavin A and B, prenylated flavones from Cannabis sativa L.
Two novel prenylated flavones, termed Cannflavin A and B, were isolated from the cannabinoid free ethanolic extract of Cannabis sativa L. Both compounds inhibited prostaglandin E2 production by human rheumatoid synovial cells in culture.
Immunosuppressive actions of prostaglandins and the possible increase in chronic inflammation after cyclo-oxygenase inhibitors.
A method is described to examine the activity of potential antirheumatic drugs on the release and activity of lymphokines and interleukins in vitro, using human peripheral blood mononuclear cells and synovial cells. The enhancement of lymphocyte-mediated effects brought about by non-steroid anti-inflammatory drugs has been shown to be the result of inhibition of a prostaglandin negative-feedback mechanism. Since the underlying features of rheumatoid arthritis and related diseases are almost certainly brought about by mononuclear cell activation, their enhancement by non-steroid anti-inflammatory drugs might well have serious clinical implications. The possibility is discussed that aspirin-like drugs, administered in large doses to patients suffering slight joint pain, might well exacerbate, perpetuate or even initiate a chronic arthritic condition. We suggest that, as soon as the disease has been diagnosed, patients should be treated with a disease-modifying drug and, if necessary, an analgesic which does not inhibit cyclo-oxygenase.
Unique properties of auranofin as a potential anti-rheumatic drug.
Gold salts, auranofin (AF), aurothiomalate (ATM) and aurothioglucose (ATG) displayed immunosuppressive action in a series of in vitro assays which mimic the cell-cell interactions thought to occur in rheumatoid arthritis. The gold salts inhibited phytohaemagglutinin (PHA)-induced thymidine incorporation and gamma-IF production by peripheral blood mononuclear cells, as well as IL-2-induced proliferation of PHA-blasts. The separate addition of IL-2 and gamma-IF partly reversed the anti-proliferative effects of ATM and ATG; however, the addition of IL-1 had no effect. ATM and ATG inhibited PHA-stimulated IL-1 production by mononuclear cells but not spontaneous or LPS-induced IL-1 production by adherent monocytes. It was concluded that ATM and ATG inhibited lymphocyte function and lymphocyte-amplification of macrophage function. The anti-proliferative effects of AF were partly reversed by IL-2 but not by gamma-IF or IL-1. AF inhibited PHA-stimulated IL-1 production by mononuclear cells as well as spontaneous and LPS-induced production by adherent cells. It appeared that AF inhibited lymphocyte and macrophage function directly. AF also displayed potential anti-inflammatory activity in that it inhibited PGE2 and collagenase production by proteolytically dispersed rheumatoid synovial cells.
Isolation from Cannabis sativa L. of cannflavin--a novel inhibitor of prostaglandin production.
The isolation from Cannabis sativa L. of an inhibitor of prostaglandin (PG) E2 production by cultured rheumatoid synovial cells is described. This agent, for which the name Cannflavin has been coined, is distinct from cannabinoids on the basis of isolation procedure, preliminary structural analysis and biological properties. The activity of Cannflavin has been compared with several established anti-inflammatory drugs and the major cannabinoids.
Structural correlations of phorbol-ester-induced stimulation of PGE2 production by human rheumatoid synovial cells.
Eight phorbol esters were studied for their ability to stimulate prostaglandin production in human rheumatoid synovial cells over the dose range 0.1 ng to 1.0 micrograms. These derivatives were based upon phorbol, 4-deoxyphorbol, and 12-deoxyphorbol nuclei. This activity was structurally dependent and, although it did not correlate with the actions of the same compounds to induce erythema in vivo, it did correlate with their ability to stimulate human lymphocyte mitogenesis. Stimulation of PGE2 production by a phorbol and a 12-deoxyphorbol analog was inhibited in this system by both indomethacin and dexamethasone.
Depression in childhood.
The concept and classification of depression in childhood is currently under review. A modern view is that childhood depression is similar to adult depressive disorders, although the extent of variation with age and sex is not yet clear. Reliable and valid diagnostic criteria are being established, which will allow a more accurate estimation of prevalence rates, aetiology, and prognosis.
Spinal cord transection and subsequent treatment with cyclophosphamide or isobutyl-2-cyanocrylate: associated microvascular abnormalities.
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Development of the rat salivary glands. II. The identification of a trypsinlike protease in the submaxillary gland.
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Behavioral growth of cerebral palsied children from group experience in a confined space.
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Drug susceptibility tests for tuberculosis using drug impregnated disks.
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