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Biomedical subjects

G J Murphy

Publications and source records attributed to G J Murphy.

83 records · Page 5Linked to original sources
PubMed1977

Screening for carotid junction disease by spectral analysis of Doppler signals.

The established test for disease in the internal carotid artery using continuous wave Doppler is to listen for flow velocity changes over the supraorbital artery with ipsilateral temporal (or facial) artery compression. This is only reliable when there is a reduction in mean pressure (and flow) distal to disease in the internal carotid artery, ie reduction of lumen diameter by more than 85%. In this study, 101 vessel segments (48 with disease at the carotid junction, 53 normal) were compared with the results of angiography. Seven gave a positive temporal artery occlusion test, all of which showed severe disease. However, spectral analysis of the Doppler signals from supraorbital and common carotid arteries showed sonagram changes both with ageing and with disease. In particular, the ratio of primary peak (A) to secondary peak (B) in systole falls, the A/B ratio being lower in disease than in health. At A/B ratios less than 1.05 there was an 88% probability of disease at the carotid junction. 36/48 (75%) diseased junctions were detected, including almost all major lesions. The method did not so reliably detect small lesions (less than 2 mm plaques, less than 60% lumen diameter stenosis, and 'minimal atheroma'). In 5/53 normal junctions the A/B ratio was in the disease range. Scanning the carotid junction for turbulence yielded additional information in some cases.

Adolescent↗
PubMedDate not supplied

Mycophenolate mofetil inhibits intimal hyperplasia and attenuates the expression of genes favouring smooth muscle cell proliferation and migration.

AIM: Intimal hyperplasia remains the leading cause of late graft failure following heart transplantation. The immunosuppressive drug mycophenolate mofetil has been shown to inhibit the development of intimal hyperplasia. This study aimed to assess the efficacy of a combination of mycophenolate mofetil, calcineurin inhibition, and sirolimus on the development of intimal hyperplasia. METHODS: Male Sprague-Dawley rats received mycophenolate mofetil (30 mg/kg per day) and either tacrolimus (0.1 mg/kg per day), cyclosporine (5 mg/kg per day), or sirolimus (0.05 mg/kg per day) and were compared to an untreated control group. All animals underwent left common carotid artery balloon angioplasty. Morphometric analysis was performed on representative transverse sections, and intima medial ratios calculated at 2 weeks. Profibrotic gene expression was assessed with competitive RT-PCR at 2 weeks for metalloproteinase-2, metalloproteinase-9, TIMP-1, collagen III, and TGF-beta. Sections were stained with sirius red, and extracellular matrix deposition was quantified. RESULTS: Mycophenolate mofetil in combination with rapamycin was associated with the greatest reduction in intimal thickening (intima medial ratio 0.79; range 0.45-0.86), compared to its combination with either cyclosporine (1.41; range 1.06-1.68, P < .02) or tacrolimus (0.93; range 0.81-1.37, P < .05) and controls (1.47; range 1.02-2.04, P < .005). Mycophenolate mofetil and rapamycin significantly inhibited all profibrotic genes studied compared to controls (P < .01) but there were no differences between tacrolimus and cyclosporine. Mycophenolate mofetil and sirolimus significantly attenuated extracellular matrix deposition compared to tacrolimus and cyclosporin (P < .023). CONCLUSION: The benefits of mycophenolate mofetil in combination with sirolimus are preferential over those with cyclosporine or tacrolimus. Randomised trials are warranted to assess if mycophenolate mofetil should be an alternative agent to calcineurin-inhibitors when used in combination with sirolimus.

Animals↗
PubMedDate not supplied

Activation of two signal-transduction systems in hepatocytes by glucagon.

The ability of glucagon to stimulate glycogen breakdown in liver played a key part in the classic identification of cyclic AMP and hormonally stimulated adenylate cyclase. But several observations indicate that glucagon can exert effects independent of elevating intracellular cAMP concentrations. These effects are probably mediated by an elevation of the intracellular concentration of free Ca2+ although the mechanism by which this occurs is unknown. We show here that glucagon, at the low concentrations found physiologically, causes both a breakdown of inositol phospholipids and the production of inositol phosphates. Indeed, we show that the glucagon analogue, (1-N-alpha-trinitrophenylhistidine,12-homoarginine)glucagon (TH-glucagon), which does not activate adenylate cyclase or cause any increase in cAMP in hepatocytes yet can fully stimulate glycogenolysis, gluconeogenesis and urea synthesis, stimulates the production of inositol phosphates. This stimulation of inositol phospholipid metabolism by low concentrations of glucagon provides a mechanism whereby glucagon can exert cAMP-independent actions on target cells. We suggest that hepatocytes possess two distinct receptors for glucagon, a GR-1 receptor coupled to stimulate inositol phospholipid breakdown and a GR-2 receptor coupled to stimulate adenylate cyclase activity.

Adenylyl Cyclases↗
PubMedDate not supplied

Side effects of cardiopulmonary bypass: what is the reality?

Despite many years of clinical and experimental research, the contribution of cardiopulmonary bypass (CPB) and cardioplegic arrest to morbidity and mortality following cardiac surgery remains unclear. This is due, in part, to lack of suitable control group against which bypass and cardioplegic arrest can be compared. The recent success of beating heart coronary artery bypass grafting has, however, for the first time, provided an opportunity to compare the same operation, in similar patient groups, with, or without CPB and cardioplegic arrest. CPB is associated with an acute phase reaction of protease cascades, leucocyte, and platelet activation that result in tissue injury. This is largely manifest as subclinical organ dysfunction that produces a clinical effect in those patients that generate an excessive inflammatory response or in those with limited functional reserve. The contribution of myocardial ischemia/reperfusion, secondary to aortic cross-clamping, and cardioplegic arrest, to the systemic inflammatory response and wider organ dysfunction is unknown, and requires further evaluation in clinical trials.

Cardiopulmonary Bypass↗