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Biomedical subjects

M Davies

Publications and source records attributed to M Davies.

At least 505 records · Page 28Linked to original sources

On the pathogenesis of glomerulonephritis: a clinico-pathological study indicating that neutrophils attack and degrade glomerular basement membrane.

Lysosomal proteinase activity was assayed in urines from 157 patients with renal disease. 16 were found to be excreting acid and neutral proteinases. 15 of these 16 had a severe proliferative glomerulonephritis with polymorphonuclear leucocyte (PMN) infiltration of the glomeruli. These same 16 patients excreted excess quantities of glomerular basement membrane (GBM) antigen. Only urines with neutral proteinase activity were capable of degrading GBM in vitro. Clinical recovery was accompanied by disappearance of both proteinases and excess GBM fragments from the urine. Detailed studies on one patient showed that the neutral proteinase activity was, at least in part, due to PMN lysosomal elastase. Calculation shows that in these patients enough PMN neutral proteinase was present in the glomeruli to cause significant GBM damage.

Antigens↗

Clinical characteristics of imipramine-induced orthostatic hypotension.

The effects of imipramine hydrochloride on blood-pressure were examined in a prospective and a retrospective study. In a prospective study of 44 depressed patients given imipramine in doses to achieve antidepressant plasma-concentrations there was no effect of the drug on lying blood-pressure. When patients then stood up, the drug produced an average fall in systolic pressure of 26 mm Hg (t = 13.6, P less than 0.001) that was consistent over the four weeks of observation. Contrary to expectation, this fall was independent of patients' age, pre-existing heart-disease, or plasma-level of the drug. The best predictor of orthostatic hypotension during treatment was the degree of orthostatic drop in pressure before treatment (r = 0.695, P less than 0.001). In order to establish the clinical significance of this orthostatic drop in pressure, a retrospective study of 148 depressed patients treated with imipramine was conducted. These 148 patients, average age 59 years, received an average dose of 225 mg of imipramine. Almost 20% of them had symptoms usually associated with orthostatic hypotension that were severe enough to interfere with their treatment: over 4% sustained physical injuries. In our experience orthostatic hypotension is the commonest serious cardiovascular side-effect of imipramine.

Adult↗

Salt taste detection: an R-index approach to signal-detection measurements.

The R-index approach to the signal-detection P(A) index of sensitivity was used to measure taste sensitivity to NaCl solutions. The R-index is the predicted probability of the correct choice of a signal, for a given signal-noise pair. For flow-wise and sipwise presentation, R-indices did not fluctuate significantly, provided subjects could not see the stimuli yet to be presented, indicating a lack of systematic sensitivity drift. The simultaneous measurement of more than one signal strength with reference to a common noise stimulus was seen to be a viable and sensitive procedure. Comparison of flow-wise and sipwise presentation of stimuli using R-indices, indicated that the former elicited greater subject sensitivity to NaCl taste.

Adolescent↗

Iron deficiency anaemia--a prospective study.

A prospective study was performed over 15 months to determine the cause of iron deficiency in adult males and postmenopausal females attending a general hospital. The laboratory computer identified all subjects with a haemoglobin less than 10.6 g/dl and a mean corpuscular volume less than 86 fl. Patients becoming anaemic after trauma or recent surgery were excluded. The iron status of each patient was assessed by serum iron studies, serum ferritin or sternal marrow aspiration. Reduced red cell indices and blood film morphology were not diagnostic of iron deficiency. Of 215 patients assessed, about half (103) were found to be iron replete. This group had a variety of disorders--malignancy, chronic inflammation, chronic renal and non-malignant haematological diseases. The other group of 104 patients satisfied criteria for iron deficiency, and 100 of these were investigated further. The cause of iron deficiency was found in all but three subjects. Inadequate dietary intake was a contributing factor in over half of the patients and 40 regularly took salicylates. Investigation defined a source of chronic gastrointestinal blood loss in most instances.

Adult↗

Albumin-coated Amberlite XAD-7 resin for hemoperfusion in acute liver failure. Part II: in vivo evaluation.

Albumin-coated Amberlite XAD-7 has been previously shown to be blood compatible in in vitro hemoperfusion experiments whith human blood. In this study, the preliminary results are reported on single hemoperfusions with albumin-coated XAD-7 resin in four patients with acute liver failure. The mean platelet count was 116+/-SE 16.3% of the initial arterial value and the mean white cell count was 96+/-SE 6.5% of initial at the end of four hours of hemoperfusion. Removal of bilirubin, phenols and substances in the middle molecular weight range by the resin was demonstrated. These preliminary results suggest albumin-coated Amberlite XAD-7 resin to be blood compatible and capable of removing protein-bound and middle molecular weight substances from patients with acute liver failure. Further clinical evaluation of repeated resin hemoperfusion is required to determine whether this treatment will be beneficial to patient survival.

Acrylic Resins↗

Dose-dependent adjuvant effects of Bacillus Calmette-Guérin on tumor immunity in Lewis rats.

The study was undertaken of the ability of Bacillus Calmette-Guérin (BCG), used in combination with a live tumor cell vaccine, to potentiate systemic antitumor immunity in rats. BCG was administered in two injections, with the first one given i.v. and the second one given intradermally mixed with the tumor cell vaccine 12 days later at the time of implant of an s.c. tumor, which served to monitor antitumor immunity. Both these BCG injections were necessary to obtain maximal protection measured in terms of increased survival rates of the rats and of decreased tumor growth rates. The dose of BCG in both the first and second injections was critical for optimal protection, since low doses (125 to 250 micrograms) afforded protection, while higher doses (over 1500 micrograms) decreased or abolished the protective effect. These results strongly suggest that BCG, only if administered under the appropriate conditions, is able to potentiate systemic tumor immunity and to provide a significant level of protection for a tumor-bearing animal.

Animals↗

The continuing risk of vitamin-D intoxication.

Eight cases of vitamin-D poisoning are described. In six patients this therapy was unnecessary and in the remaining two patients inadequate supervision of the treatment resulted in overdosage. In five cases the history of vitamin-D therapy was either unknown or not appreciated by the referring clinician so that three surgical procedures of dubious value were performed on two patients. Large doses of vitamin D should only be used when strictly indicated and on the understanding that close biochemical and clinical supervision is necessary.

Adolescent↗

The binding of lipopolysaccharide from Escherichia coli to mammalian cell membranes and its effect on liposomes.

The kinetics of the absorption of 32P- or 14C-labelled lipopolysaccharide from Escherichia coli NCTC 8623, serotype 0 125, chemotype XII, to erythrocytes, leukocytes, peritoneal macrophages and peritoneal lymphocytes was examined. Under variable conditions maximal levels of binding were found due to saturation of receptor sites on the cell membrane or steric hindrance by bound lipopolysaccharide. During adsorption slight leakage of haemoglobin was found but complete lysis of erythrocytes was ruled out after noting the effect of lipopolysaccharide on artificial lipid bilayers. The affinit of lipopolysaccharide to cell membranes revealed a consistent pattern of cyclic fluctuation between adsorption and desorption. A model was proposed to explain this cyclic fluctuation in binding based on membrane reorganization. It was significant that the cycle of lipopolysaccharide adsorption-desorption proceeded to completion even if the process was interrupted. The indication was that, once triggered, membrane reorganization occurred independently without influence from the test environment.

Animals↗

The degradation of human glomerular basement membrane with purified lysosomal proteinases: evidence for the pathogenic role of the polymorphonuclear leucocyte in glomerulonephritis.

1. Human polymorphonuclear leucocyte elastase and cathepsin G were incubated with preparations of isolated human glomerular basement membrane at neutral pH and 37 degrees C. 2. The ability of these enzymes to degrade glomerular basement membrane was followed by the release of hydroxyproline. Both proteinases released considerable amounts of hydroxyproline. 3. By using Sephadex G-100 it was shown that the solubilized basement membrane fragments appeared as a single peak and had a molecular weight of over 100 000. These proteins after reduction were analysed by sodium dodecyl sulphate-gel electrophoresis to examine their subunit pattern and determine their molecular size. 4. The released basement membrane proteins gave at least four precipitin lines with a rabbit anti-(glomerular basement membrane) antiserum. 5. These results support the concept that polymorphonuclear leucocyte neutral proteinases play an important role in the pathogenesis of glomerulonephritis. 6. At acid pH values cathepsin B also released hydroxyproline from human glomerular basement membrane but the lysosomal carboxyl proteinase, cathepsin D, had no action.

Basement Membrane↗