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Biomedical subjects

M Vickers

Publications and source records attributed to M Vickers.

35 records · Page 2Linked to original sources

The isolation and characterization of magnesium whitlockite crystals from human articular cartilage.

A number of basic calcium phosphate crystals have been demonstrated in human articular tissues. The exact relationship between crystal deposition and disease remains obscure, although there is evidence supporting a rapid degenerative arthropathy within a specific set of patients. Limited reports of 'cuboid' calcium phosphate microcrystals in articular cartilage have been made over the last 10 years. In this study the occurrence of such crystals, not apparent by light microscopy, in human articular cartilage has been confirmed by transmission electron microscopy and X-ray microanalysis of tissue prepared by aqueous and anhydrous processing techniques. A crystal isolation technique involving collagenase digestion, centrifugation and sodium hypochlorite treatment was developed enabling crystal characterization by electron and X-ray diffraction. Crystals were identified as magnesium whitlockite; the first report of this mineral in articular cartilage. The presence of this mineral phase in normal and osteoarthritic articular cartilage is discussed with consideration given to physical conditions known to favor whitlockite formation and those extant in articular cartilage.

Calcium Phosphates↗

t(8;21) myelodysplasia, an early presentation of M2 AML.

The reciprocal translocation of genetic material between chromosomes 8 and 21, t(8;21), is usually restricted to cases of acute myeloid leukaemia (AML). Cases of AML with t(8;21) exhibit characteristic dysplastic features in myeloid and erythroid lineages with reduction in megakaryocytes. We report details of three patients presenting with myelodysplastic features; two had a typical t(8;21), and the third had a variant t(8;21) translocation. We discuss the significance of t(8;21) in the aetiology of myelodysplastic syndrome (MDS) and implications for the management of such patients.

Adult↗

Quantification of urinary insulin-like growth factors (IGFs) and IGF binding protein 3 in healthy volunteers before and after stimulation with recombinant human growth hormone.

We examined excretion of urinary insulin-like growth factors I and II (IGF-I and IGF-II) and their major binding protein IGFBP-3 in comparison to their respective serum concentration in nine healthy female volunteers (median age 25 years, range 22-27) under baseline conditions and after stimulation with recombinant human growth hormone (rhGH), 4.5 IU twice daily subcutaneously for a period of 3 days. The IGFs were measured in unconcentrated urine by use of recently developed, highly sensitive radioimmunoassays. The IGFBP-3 was measured by a specific radioimmunoassay. The mean (+/- SD) urinary concentrations of IGF-I (0.08 +/- 0.07 micrograms/l), IGF-II (1.02 +/- 0.47 micrograms/l) and IGFBP-3 (19.1 +/- 6.9 micrograms/l) were two to three orders of magnitude lower than in serum. The ratio of IGF-II over IGF-I concentration in urine (13:1) was five times higher than in serum (2.5:1), and the ratio of IGFBP-3 over the sum of IGF-I and IGF-II in urine (17:1) was four times higher than in serum (4:1). Urinary excretion was 63.3 +/- 46.6 ng.m-2.24h-1 for IGF-I, 1002 +/- 598 ng.m-2.24h-1 for IGF-II and 18039 +/- 4983 ng.m-2.24h-1 for IGFBP-3. Using fast protein liquid exclusion chromatography, only immunoreactive IGFBP-3 components of less than 60 kD were detected in urine, with a major peak at 20 kD. Urinary IGFBP-3 excretion correlated with serum IGFBP-3 (r = 0.61, p < 0.01) and the glomerular filtration rate (r = 0.56, p < 0.05) measured by steady-state inulin infusion clearances.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Response of T-beta CD8+ lymphocytosis-associated neutropenia to G-CSF.

Only limited data are reported on the response to granulocyte-colony stimulating factor (G-CSF) of large granular lymphocytosis-associated neutropenia. We report features of such a case who developed a suppurating leg ulcer following a dog bite. G-CSF was used to increase the neutrophil count, allowing the ulcer to be successfully skin grafted.

Female↗

Quality of platelet concentrates irradiated with UVB light: effect of UV dose and dose rate on glycocalicin release and correlation with other markers of the platelet storage lesion.

The amount of membrane-associated glycoprotein Ib in platelet concentrates (PCs) irradiated with a high dose of UVB light has been shown to be significantly reduced after 48 h storage. We recently corroborated this finding when we noted an increase in the supernatant levels of glycocalicin (GC, a major segment of glycoprotein Ib) in UVB-treated PCs during storage. The aim of the present study was to determine whether GC release was related to both the UV dose and the rate of dose delivery. Plateletpheresis concentrates obtained from five donors were pooled and split into five equal parts. Four of these were treated with 7500 and 15,000 mJ/cm2 UVB using two prototype UV sources with differing rates of dose delivery; namely, Baxter (BAT) and British Aerospace (BAC) cabinets, with the latter having the slower rate of delivery. On days 1 and 5 of storage, GC levels in the supernatants of PCs were determined by ELISA. Moreover, the following parameters were also assessed: platelet and WBC count; hypotonic shock response (HSR) and platelet aggregation response to ADP, ADP+collagen, ADP+arachidonic acid and ristocetin; pH; supernatant levels of lactate, glucose, von Willebrand factor (vWf) and beta-thromboglobulin (beta TG). The results revealed an association of GC release with UVB dose using both UV sources, although this was more apparent in the BAC system, in which glycocalicin release at day 5 of storage was as follows (microgram/ml, mean +/- SD): 4.8 +/- 0.3 and 9.5 +/- 3.6 at 7500 and 15,000 mJ/cm2 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗

Induction of CYP1A1 gene expression in H4-II-E rat hepatoma cells by benzo[e]pyrene.

In the rat, expression of the CYP1A1 gene is closely associated with arylhydrocarbon hydroxylase (AHH) enzyme activity. AHH is an inducile enzyme activity known to play an important role in the bioactivation of polycyclic aromatic hydrocarbons (PAHs) to mutagenic and carcinogenic metabolites. PAH-induced expression of the CYP1A1 gene appears to be regulated by several trans-acting factors, including the Ah receptor and the 4S PAH-binding protein. In this study, we used the PAH isomers benzo[a]pyrene (BaP) and benzo[e]pyrene (BeP) to further evaluate the role of the 4S PAH-binding protein in induction of the CYP1A1 gene in H4-II-E rat hepatoma cells. Although BaP is believed to bind to both the Ah receptor and the 4S protein, BeP has been reported to bind exclusively to the 4S protein. The results of the study presented here indicate that BaP and BeP induce the expression of the CYP1A1 gene, as measured by ethoxyresorufin O-deethylase (EROD) activity, in a concentration-dependent manner. However, BaP is about 25 times as potent as BeP in inducing EROD activity in these cells. Slot-blot analysis of total RNA isolated from these cells indicated that BeP, BaP, and 3-methylcholanthrene increased the level of CYP1A1 mRNA expression. Sucrose-gradient analysis of BeP binding activity indicated that BeP bound with high affinity to the 4S PAH-binding protein, but not to the Ah receptor. These results suggest that the 4S protein may play a role in the PAH-induced expression of the CYP1A1 gene in rat H4-II-E cells.

Animals↗

Effects of a fish oil supplement on platelet function, haemostatic variables and albuminuria in insulin-dependent diabetics.

A randomised trial of the effects of 15 gm per day of a fish oil supplement (MaxEPA) on blood lipids, haemostatic variables (including platelet function) and albuminuria was undertaken in 41 insulin dependent diabetics. Compared with the control group there was a significant reduction in thromboxane production by platelets stimulated by collagen in vitro in the group who took the fish oil supplement. The extent of platelet aggregation was not altered but the lag phase before aggregation was prolonged. There were also statistically significant increases in plasma LDL cholesterol, fibrinogen and clotting factor X in the group who took the fish oil supplement. No other significant differences were noted.

Administration, Oral↗

Effect on blood lipids and haemostasis of a supplement of cod-liver oil, rich in eicosapentaenoic and docosahexaenoic acids, in healthy young men.

1. Twelve healthy male subjects took a daily supplement of 20 ml of cod-liver oil for 6 weeks. This provided 1.8 g of eicosapentaenoic acid (20:5 omega 3) and 2.2 g of docosahexaenoic acid (22:6 omega 3). The effects of the supplement on blood lipids, haemostatic variables, bleeding time and plasma vitamin A and carotene were studied. In seven subjects platelet aggregation induced by adenosine 5'-pyrophosphate (ADP) was also studied. 2. The proportions of 20: 5 omega 3 and 22: 6 omega 3 in platelet and erythrocyte phosphoglycerides were substantially increased by the supplement mainly at the expense of omega 6 polyunsaturated fatty acids. 3. Mean plasma triglyceride concentrations were reduced and those of high-density-lipoprotein (HDL) cholesterol were increased by the supplement. 4. The mean bleeding time was significantly prolonged after 3 weeks of taking the supplement, but had returned to the presupplementation value 5 weeks after withdrawal of the supplement. 5. The maximum estimated response to platelet aggregation induced by ADP was increased by the supplement. 6. The mean levels of antithrombin III (immunological) and blood pressure were lower at the end of the period of supplementation and remained so 5 weeks after withdrawal of the supplement. No significant changes in other variables were noted.

Adult↗

Effect of treatment of hyperlipidaemia on haemostatic variables.

The haemostatic function of 11 men with hyperlipidaemia was measured before and after they were treated with a carbohydrate-reduced, fat-modified diet. After treatment, which significantly reduced serum triglyceride and cholesterol concentrations, they showed a significant fall in mean levels of clotting factors VII, VIII, and X and a rise in fibrinolytic activity. These findings suggest that haemostatic function may be important in the pathogenesis of ischaemic heart disease.

Adult↗

Automation of two-stage factor VIII assay.

Two automated methods for two-stage factor VIII assays have been compared with one another, and evaluated in practice. The Depex method records the clotting time when an electric circuit is completed by the formation of a fibrin thread across a hook-type electrode; the Electra method is based on an optical density technique of clot detection. The two methods gave comparable results for measured levels of factor VIII when haemophilic or "normal" plasmas were assayed. Results from the two methods in practice also suggest that both are valid at low and "normal" factor VIII levels. The Electra method is also probably suitable for assays of concentrates; however, the Depex method appears to give falsely high values in these circumstances, and experimental findings suggest that the reason may be that increased viscosity due to the high fibrinogen levels in factor VIII concentrates causes premature closure of the circuit between the two ends of the Depex electrode. The main advantage of the Depex method is that, provided 3 or 4 machines are available, a given number of assays can be completed more quickly than on Electra. The main advantages of Electra are that it is probably subject to less laboratory error than Depex, and that it is suitable for assaying concentrates as well as haemophilic and "normal" plasmas.

Automation↗

An assessment of one year of computer-assisted microbiology reporting at Charing Cross Hospital.

The pilot scheme began in August 1972 after three months of running parallel with a conventional system. In October 1972 the system was moved from Fulham Hospital into the new Charing Cross Hospital. Sixty thousand routine bacteriology requests have been processed satisfactorily by the computer system, about 70% of the total received. The cost for a computer-printed report is 32p compared with 6p for a typed one.

Bacteriological Techniques↗