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Biomedical subjects

M J James

Publications and source records attributed to M J James.

At least 73 records · Page 4Linked to original sources

Inhibition of human endothelial prostacyclin synthesis by different aspirin formulations.

The availability of different formulations of low-dose aspirin for use as anti-thrombotic agents merits a comparison of their effects on vessel wall biochemistry. We compared the effect of ingestion of an enteric-coated slow-release aspirin (Astrix) with that of soluble aspirin (Cardiprin) on human endothelial prostacyclin synthesis. Patients undergoing varicose vein surgery (10 per group) ingested 100 mg aspirin per day as Astrix or Cardiprin for 7 days prior to surgery. A control group ingested no aspirin. Prostacyclin synthesis by the endothelial surface of the great saphenous vein was determined in vitro. Both aspirin formulations caused significant inhibition of endothelial prostacyclin synthesis compared with the control group. Using the median values, the enteric-coated slow-release aspirin caused 76% inhibition, whereas the soluble formulation caused significantly greater inhibition (95%). If differential inhibition of platelet thromboxane synthesis with 'sparing' of endothelial prostacyclin synthesis is necessary for an optimum anti-thrombotic effect of aspirin, the results suggest that a lower dose of soluble aspirin than enteric-coated slow-release aspirin may be preferred.

Aspirin↗

Effect of dietary oils on the production of n-3 and n-6 metabolites of leukocyte 5-lipoxygenase in five rat strains.

We examined the influence of various dietary oils, including linseed and fish oil on the relative rates of leukotriene B4 (LTB4) and LTB5 production by rat peritoneal exudate cells in five rat strains. While there was an association between the membrane phospholipid levels of the fatty acid precursors (arachidonic acid (AA) and eicosapentaenoic acid (EPA)) and the rate of synthesis of their respective 5-lipoxygenase products (LTB4 and LTB5), the rate of LTB4 synthesis was a combined function of both AA and EPA levels. We observed a strong linear relationship (correlation coefficient = 0.99) between the ratio of EPA/AA in the cell membrane phospholipids and the ratio of LTB5/LTB4 produced by these cells in vitro; this association was independent of genetic (strain) variability and was independent of the source of EPA (dietary EPA or EPA endogenously synthesized from dietary alpha-linolenic acid).

Animals↗

Comparison of cell membrane phospholipid fatty acids in five rat strains fed four test diets.

The fatty acid composition of phospholipids in peritoneal exudate cells and spleen cells was assessed in five rat strains fed four test diets of differing fatty acid composition. Distinctive patterns of fatty acids were seen in the total phospholipid preparations in both cell types in response to the diets which contained either olive, sunflower, linseed or fish oil. In general, similar fatty acid profiles were seen in each of the rat strains fed the same diet with the only evidence of possible genetic (strain) variation being a relative deficiency of delta 4 desaturase in Dark Agouti rats.

Animals↗

Vascular outflow resistance and angiographic assessment of lower limb arterial reconstructive procedures.

In an attempt to predict early graft occlusion secondary to poor distal run-off, the outflow resistance was measured intra-operatively and compared with the intra-operative angiogram in 50 patients undergoing lower limb bypass procedures. With arterial inflow occluded, 60 mL of plasmalyte was infused via a catheter and the resultant pressure generated in the graft was measured through a second catheter connected to a pressure transducer and recorder. Using the infusion rate and integrated pressure value, outflow resistance was calculated. High resistance measurements were defined as grafts with outflow resistance greater than 1.1 mmHg/mL per min, low measurements were defined as values less than 0.5 mmHg/mL per min and intermediate measurements were those in the range 0.5-1.1 mmHg/mL per min. Angiograms were classified independently of resistance measurements by scoring the numbers of run-off vessels crossing the ankle and stenoses, with subsequent assignment of the patient to one of three groups with either low, intermediate, or high probability of graft failure. Early graft failure was defined as cessation of graft function within 3 months of surgery. Early graft failure occurred in both cases with high outflow resistance and in seven of 44 with low outflow resistance. Of these nine occluded bypasses, six had been placed in the high probability of occlusion category on angiographic appearance and three in the intermediate category. Assessment of angiographic appearance and prediction of patency on a prospective basis had a sensitivity rate of 67% and a specificity rate of 78%. The corresponding sensitivity and specificity rates with resistance measurements were 22% and 100%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Intraarticular pressure and the relationship between synovial perfusion and metabolic demand.

We examined the influence of intraarticular pressure on products of synovial energy metabolism in patients with knee effusions. A range of intraarticular pressures was generated by controlled flexion. Pressures greater than or equal to 45 mm Hg were associated with increased synovial fluid lactate concentrations and pCO2, and decreased pH. Our results suggest that pressures greater than or equal to 45 mm Hg, which we also observed during standing and walking, can cause synovial ischemia and hypoxia manifest in a perfusion/metabolic demand mismatch. Monitoring changes in SF concentrations of uric acid did not provide consistent evidence for accelerated purine degradation following periods of inadequate perfusion. Overall, our results suggest that synovial blood flow can be compromised by modest elevations in intraarticular pressure in the range encountered during daily activity in patients with knee effusions.

Adult↗

Measurement of aspirin concentrations in portal and systemic blood in pigs: effect on platelet aggregation, thromboxane and prostacyclin production.

Low doses of enteric-coated aspirin were administered orally to pigs. Plasma aspirin concentrations measured in blood obtained simultaneously from permanent catheters in a systemic artery and portal vein for 6 hours after dosage showed a large variation in the plasma aspirin concentration: time profile between pigs. After 50 mg single dose the ratio of the arterial: portal area under the plasma concentration versus time curve (AUC) was 0.63 +/- 0.08 (mean +/- SE, n = 6). In three pigs which received all three dosage regimens, the arterial: portal AUC ratios were 0.48 +/- 0.05 after 50 mg single dose, 0.52 +/- 0.02 after 100 mg single dose and 0.47 +/- 0.02 after 100 mg daily for 1 week. Platelet aggregation in response to sodium arachidonate (1.65 mM) was completely abolished after chronic aspirin administration of 100 mg daily. Thromboxane production (pg/10(6) platelets) induced by this stimulus decreased from 536 +/- 117 before aspirin to 57 +/- 14 after aspirin (mean +/- SE, n = 4; p = 0.03). Aortic prostacyclin synthesis, measured as 6-keto PGF1 alpha (ng/disc after 10 min incubation), was 1.66 +/- 0.28 (mean +/- SE, n = 4) in untreated pigs and 0.95 +/- 0.25 (n = 5) in treated pigs (p = 0.07). Results from this study support the idea that a difference between aspirin concentrations in the portal and systemic circulations can be achieved. Whether this can be translated into a clinically useful differential effect on the vessel wall compared to the platelet remains to be determined.

Animals↗

Choledochoscopy via the cystic duct: evaluation of a new ultrathin disposable choledochoscope.

A 2 mm fibreoptic choledochoscope with a disposable (resterilisable) flexible section was evaluated in 25 cadavers and 13 patients undergoing cholecystectomy. It was possible to pass the instrument via the cystic duct (CD) into the common bile duct (CBD) in 23 out of 25 cadavers and in 12 out of 13 patients. The CD diameter in cadavers was 2.4 mm (SD 0.5). Optical clarity was excellent and it was easy to pass into the duodenum, but proximal passage required mobilisation of the CD/CBD junction. This instrument may be a useful adjunct or even an alternative to intraoperative cholangiography.

Common Bile Duct↗

Inter-relationships between vascular thromboxane and prostacyclin synthesis.

We have measured the effect of various concentrations of arachidonic acid on the rates of synthesis of prostacyclin and thromboxane in human umbilical artery slices. Increasing concentrations of arachidonate increased the rate of thromboxane synthesis, but had no effect on the rate of prostacyclin synthesis. However, in dexamethasone-treated artery slices, arachidonate increased the rate of thromboxane and prostacyclin synthesis. Overall, it was demonstrated that arachidonate can alter the ratio of prostacyclin/thromboxane synthesis in untreated artery slices and, by inference, arachidonate can alter the thrombogenicity of vascular endothelium. A mechanism is proposed to explain the arachidonate-induced changes in the prostacyclin/thromboxane ratio.

Arachidonic Acid↗

Effect of 50 mg enteric-coated aspirin (Astrix) on thromboxane and prostacyclin synthesis.

Although low-dose soluble aspirin can be recommended as a useful anti-thrombotic drug regimen in patients with vascular disease, enteric-coated preparations have a theoretical advantage for aspirin preparations which are to be ingested daily for many years. We have demonstrated that a 50 mg enteric-coated aspirin formulation (Astrix) which has an absorption rate much lower than soluble aspirin, is sufficient to inhibit platelet thromboxane synthesis while causing no major decrease in vascular prostacyclin synthesis.

Aspirin↗

Transluminal balloon angioplasty in diabetic peripheral vascular disease.

Transluminal (balloon) angioplasty of iliac or superficial femoral stenoses in 18 diabetic patients resulted in a significant improvement in ankle/brachial systolic pressure index with marked symptomatic improvement in 16, little change in one and deterioration requiring arterial bypass surgery in one patient. Follow-up for 12 months or more showed that the initial good results were sustained despite a downward drift in ankle pressures. These findings indicate that transluminal angioplasty has a useful place in the management of proximal atherosclerotic stenotic lesions in diabetic patients with symptomatic peripheral vascular disease.

Aged↗

An improved method for the preparation and culture of urothelial cells.

Urothelial cells have been prepared by a new method involving collagenase treatment of the lumen of a ureter. These cells have been identified as epithelial and successfully subcultured. In addition, we have observed that growth rate is significantly increased by the inclusion of an extract of bovine hypothalamus in the growth medium. This system for cell preparation and culture should greatly facilitate studies involving urothelial cells.

Animals↗

Lack of correlation between in vitro and in vivo effects of low density lipoprotein on the inflammatory activity of monosodium urate crystals.

The effect of coating monosodium urate crystals (MSU) with low density lipoprotein (LDL), postulated previously as a major regulator of gouty inflammation, was studied in a neutrophil chemiluminescence (CL) assay and an air pouch model of inflammation induced by MSU. LDL crystalline coating abrogated the neutrophil CL response but, in contrast, had no inhibitory effect on leucocyte accumulation, levels of the prostaglandin (PG) metabolite 6-keto-PGF1 alpha, and exudation of plasma proteins in the in vivo model. This latter observation raises doubts about the postulated physiological role of LDL in terminating the acute gouty attack.

6-Ketoprostaglandin F1 alpha↗

Stability of intravenous admixtures containing aztreonam and cefazolin.

The stability of aztreonam and cefazolin in intravenous admixtures was studied. Each of the following combinations of drugs was added to both 5% dextrose injection and 0.9% sodium chloride injection in polyvinyl chloride containers: aztreonam 20 mg/mL and cefazolin 20 mg/mL (as the sodium salt); aztreonam 10 mg/mL and cefazolin 5 mg/mL; aztreonam 20 mg/mL and cefazolin 5 mg/mL; and aztreonam 10 mg/mL and cefazolin 20 mg/mL. One of each of these admixtures was stored at 23-25 degrees C for 48 hours and at 4-5 degrees C for seven days. At various storage times the admixtures were inspected for visual changes, and 1-mL samples were tested for pH and assayed using a stability-indicating high-performance liquid chromatographic assay. No visual changes were observed, and changes in pH were negligible. Concentrations of aztreonam and cefazolin under both storage conditions decreased by less than 3%. Intravenous admixtures of aztreonam and cefazolin at the concentrations studied are stable for at least 48 hours at 23-25 degrees C and for seven days at 4-5 degrees C.

Aztreonam↗

Effects of aspirin and alcohol on platelet thromboxane synthesis and vascular prostacyclin synthesis.

We have studied interactions between aspirin and alcohol in vitro with regard to their effects on platelet thromboxane synthesis and vascular prostacyclin synthesis. Alcohol did not affect the inhibition by aspirin of platelet thromboxane synthesis. However, low concentrations of alcohol (0.05-0.15%, v/v) reversed the inhibition by aspirin of vascular prostacyclin synthesis. Since the effects on prostacyclin and thromboxane synthesis would favour bleeding rather than haemostasis, the observations reported herein may explain previous reports of a potentiation by alcohol of the aspirin-induced increase in bleeding time.

Aspirin↗

Peritoneal fluid 6-keto prostaglandin F1 alpha levels in women with endometriosis.

Peritoneal fluid was collected from women undergoing investigations for infertility at laparoscopy performed during the luteal phase. The volume of fluid was recorded and concentrations of 6-keto prostaglandin F1 alpha were determined by radioimmunoassay. No difference was found in either the total amount or the concentration of 6-keto prostaglandin F1 alpha in the women with or without endometriosis. Furthermore, there was no difference in the volume of peritoneal fluid between these two groups of women. We conclude that 6-keto prostaglandin F1 alpha in peritoneal fluid is not associated with macroscopically visible endometriosis.

6-Ketoprostaglandin F1 alpha↗

Stability of intravenous admixtures of aztreonam and ampicillin.

The stability of aztreonam and ampicillin in intravenous admixtures containing both drugs was studied. Each of the following drugs and combinations of drugs was added to both 5% dextrose injection and 0.9% sodium chloride injection: aztreonam 10 and 20 mg/mL, ampicillin sodium 5 and 20 mg/mL, aztreonam 20 mg/mL and ampicillin sodium 20 mg/mL, aztreonam 20 mg/mL and ampicillin sodium 5 mg/mL, aztreonam 10 mg/mL and ampicillin sodium 20 mg/mL, and aztreonam 10 mg/mL and ampicillin sodium 5 mg/mL. One of each of these admixtures was stored at 25 degrees C for 48 hours and 4 degrees C for seven days. At various storage times the admixtures were inspected for visual changes and 2-mL samples were examined microscopically for crystalline and particulate matter, tested for pH, and assayed by high-performance liquid chromatography. No visual changes were observed. In the two-drug solutions, pH was influenced by concentrations of the two drugs and stability of the drugs was influenced by the solution pH. The pH of single-drug aztreonam admixtures did not change during storage, but the pH of single-drug and two-drug admixtures containing ampicillin decreased. In single-drug admixtures, aztreonam loss under both storage conditions was less than 10% but ampicillin loss was more than 10% in 0.9% sodium chloride injection and more than 50% in 5% dextrose injection. The stability of ampicillin was increased in the presence of aztreonam, and the stability of aztreonam was decreased in the presence of ampicillin.(ABSTRACT TRUNCATED AT 250 WORDS)

Ampicillin↗