Biomedical subjects
Publications and source records attributed to L M Smart.
We wish to report the progress of a patient with pyoderma faciale and Crohn's disease. The patient is interesting in that on two occasions the relapse in her skin condition coincided with the introduction of non-steroidal anti-inflammatory drugs. Therapy with isotretinoin was effective and well tolerated.
The introduction of new GP contracts in April 1990 incorporated a financial incentive to undertake minor surgical procedures. Previous reports have noted large increases in the number of GP-derived skin specimens after April 1990. Our present study intended to address whether similar changes have occurred in Grampian Region as well as, more specifically, noting whether there have been changes in the quality of practice following the 1st April 1990. A retrospective study of skin biopsies removed by general practitioners in Grampian Region was undertaken. Cases were selected from four periods of six months (1st April to end of September) in 1987, 1988, 1989 and 1990. All skin specimens sent by general practitioners to the Department of Pathology, Aberdeen Royal Infirmary, were included. Following April 1990 there was a two-fold increase in skin specimen numbers--an increase significantly greater than increases observed over previous years (p < 0.01). Of particular note was the contribution made to this increase by Aberdeen City GPs whose contribution rose five-fold (p < 0.0001). Non-benign lesions (ie malignant plus carcinoma-in-situ-) represented 6% of lesions excised. A non-benign clinical diagnosis or an indication of suspicion was written on only one third of request forms for histopathologically diagnosed non-benign lesions. The proportion of histologically incompletely excised lesions rose over the four years (p < 0.01); moreover the increase in total numbers of lesions resulted in a striking increase in the actual numbers of incompletely excised lesions after April 1990.
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Seven cases of neonatal pulmonary sequestration are reviewed which illustrate the varied clinical presentations and radiological findings. In four patients, real time ultrasound scanning was used to image the chest and the features are described. In three cases, the systemic supplying artery was demonstrated by duplex Doppler scanning and further invasive investigations were avoided; after a chest radiograph, this should be the examination of choice in the investigation of a neonate with a possible pulmonary sequestration.
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Cyclosporin A (CsA) has become established as the agent of choice for the prevention of organ allograft rejection and has shown considerable promise in the clinical management of certain autoimmune disorders. The impact of CsA as an immunotherapeutic agent of major importance is attributable to its powerful, selective inhibitory action on T-lymphocyte activation and proliferation. Moreover, CsA lacks the myelotoxic and other major side effects associated with cytotoxic immunosuppressive agents, such as cyclophosphamide or azathioprine. It is now clear that CsA has a potential therapeutic role in the treatment of malignancies, especially T-cell cancers. Recent studies suggest that there may be several areas of application for CsA, either as a direct antiproliferative agent or in combination with other drugs, including inhibitors of polyamine biosynthesis or cytotoxic anti-tumour agents, including vincristine and adriamycin. In addition, CsA and non-immunosuppressive analogues have been shown to restore multi-drug sensitivity in cancer cells with acquired drug resistance. A further application of CsA may be to prevent the induction of human immune responses to therapeutic mouse monoclonal antibodies directed against tumour antigens, thereby enhancing the efficiency and safety of this form of cancer immunotherapy. Due to our incomplete understanding of the antiproliferative properties of CsA, further exploration of its potential as an anti-tumour agent must be accompanied by detailed studies aimed at elucidating its action on subcellular molecular events in both normal and malignant cells.
We have examined the influence of cyclosporin A (CsA), administered together with the polyamine antimetabolite, alpha-difluoromethylornithine (DFMO), on growth of the Roser acute T-cell leukaemia in PVG rats and on growth of the EL4 lymphoma in C57BL/6 mice. CsA or DFMO alone, administered from the time of tumour injection, markedly reduced numbers of circulating lymphoblasts in leukaemic rats, although survival was prolonged only in those animals given DFMO. Drug combination further reduced blood-borne tumour cells, but had no additional effects on tumour growth within organs or on host survival, compared to that achieved with DFMO treatment alone. Neither CsA nor DFMO, administered from the time of tumour-cell injection, nor both drugs in combination, affected peritoneal growth of the EL4 lymphoma or organ infiltration. Host survival was prolonged by DFMO. As anticipated, DFMO inhibited polyamine synthesis in vivo, but the observed anti-tumour effect of CsA was not accompanied by an alteration in polyamine biosynthesis. By reducing polyamine synthesis, however, DFMO may enhance the vulnerability of those malignant T cells which are susceptible to the as yet unexplained selective inhibitory action of CsA in vivo.
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Our objective was to examine the effect of cyclosporin A (CsA; 25 or 12.5 mg/kg) on growth of an acute (Roser) T-cell leukaemia in male PVG rats. The leukaemic blasts were shown (by immunocytochemical analysis) to have a mature, T-helper-cell phenotype, i.e., OX-19 (CD5) +/- , W3/25 (CD4)+, OX44+, MHC-class I+, OX-26+, corresponding to a population comprising 5% of normal rat medullary thymocytes. Animals received 20 X 10(3) viable tumour cells intramuscularly (day 0) and were given either CsA (25 or 12.5 mg/kg) or drug vehicle by gavage from day 0 or day 14, by which latter time leukaemic blasts normally appeared in the circulation. Administration of the higher dose of CsA from day 0 or day 14 significantly delayed the appearance of leukaemic cells in the peripheral circulation, whereas treatment with 12.5 mg/kg was without significant effect. CsA whole blood levels on day 17 were twice as high in leukaemic rats as in normal controls. Leukaemic infiltration of the spleen and the liver was reduced on day 17 after 25 mg/kg CsA, but no such effect was observed in lymph nodes or kidneys. A heterogeneous, host "reactive" cell population, which developed in response to the leukaemia, was inhibited by CsA, indicating that the effect of the drug was probably not mediated by host defence mechanisms. In CsA-treated leukaemic animals, there was biochemical evidence of synergistic impairment of glomerular and tubular function.
The relative value of fructosamine as an alternative to glycosylated hemoglobin (HbA1) and other measures of glycemic control was assessed in 100 insulin-dependent (IDDM) and 104 non-insulin-dependent (NIDDM) diabetic patients. We measured HbA1 (by electrophoretic and affinity methods), plasma glucose, glycosylated plasma proteins, and fructosamine in blood taken at a single clinic visit. The values were compared both by correlation analysis and by considering whether the various indices of glycemic control placed the patients in the same clinical decision categories as they were in by the HbA1 (affinity) result. Fructosamine correlated moderately well with HbA1 (affinity; r = .8) and placed 71% of IDDM and 72% of NIDDM patients in the same clinical category of good, moderate, or poor control. Differences can probably be partly attributed to the different periods over which HbA1 and fructosamine reflect average glycemia and partly to imprecision.
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The values of several non-invasive methods for the diagnosis of right ventricular necrosis in inferior myocardial infarction were compared in 51 consecutive patients who underwent serial radionuclide ventriculography, pyrophosphate scintigraphy, and cross sectional echocardiography. In addition a unipolar electrocardiographic lead V4R was recorded on admission, daily, and during episodes of further pain. Profound right ventricular dysfunction was evident in 50% of patients studied by radionuclide methods after inferior myocardial infarction but recognition on clinical groups alone was poor. Functionally important right ventricular infarction was best detected and followed serially by radionuclide ventriculography. Echocardiographic methods for evaluating right ventricular ejection fraction correlated poorly with radionuclide methods. Increased uptake of radioactivity by the right ventricle on pyrophosphate scintigraphy usually indicated poor right ventricular function, but a scan that was negative in the right ventricular territory did not exclude dysfunction. ST segment elevation in V4R was not specific for right ventricular infarction and its routine use may lead to overdiagnosis of this condition. Serial measurements suggest that profound right ventricular dysfunction persists after acute inferior infarction and is associated with considerable morbidity and mortality. Of 25 patients with severe right ventricular dysfunction, six died in the late hospital period. In the remaining 19 patients mean right ventricular ejection fraction over a two month period did not improve; six patients had persistent right ventricular dyskinesia and features of chronic right ventricular failure developed in three survivors.
Antibody coating of bacterial isolates has been proposed as a method of identifying bacteria responsible for chronic lower respiratory infections. This study was designed to determine the specificity of antibody coating by examining bronchial secretions obtained from a group of patients with chronic bronchitis who had no clinical evidence of acute infection. Routine and quantitative bacterial cultures were performed at the same time. The bronchial brush specimens contained potentially pathogenic bacteria in all 18 patients examined, and 17 of these 18 specimens had antibody coating of bacteria. Quantitative cultures yielded greater than 10(4) colony forming units in only one patient and he subsequently developed a lower respiratory tract infection. We conclude that in patients with chronic bronchitis, the determination of antibody coating of bacterial isolates does not significantly increase the specificity of routine culture. Quantitative cultures of specimens obtained via the protected brush catheter are useful in identifying potential pathogens.
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