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Biomedical subjects

N L Browse

Publications and source records attributed to N L Browse.

At least 37 records · Page 2Linked to original sources

Effects of cigarette smoke, carbon monoxide and nicotine on the uptake of fibrinogen by the canine arterial wall.

An animal model has been used to investigate the effects of cigarette smoke, carbon monoxide and nicotine on the uptake of 125I-labelled fibrinogen by the arterial wall. The uptake of fibrinogen in the smoking group (5.5 +/- 2.8 counts.cm-2 x 10(-4)) and carbon monoxide group (6.1 +/- 2.7 counts.cm-2 x 10(-4)) was greater than the uptake in the control group (4.5 +/- 1.4 counts.cm-2 x 10(-4)) but this difference was not significant. In the nicotine group, there was a highly significant increase in wall uptake of 125I-fibrinogen (9.1 +/- 2.1 counts.cm-2 x 10(-4)) (P less than or equal to 0.001). These results suggest that nicotine, a major constituent of cigarette smoke, increases the retention of 125I-fibrinogen by the arterial wall and that this might be one mechanism by which cigarette smoking exerts its atherogenic effect.

Animals↗

The CHAT classification of stroke.

Current terminology for clinical episodes relating to stroke is inconsistent and unclear, does not permit inclusion of data regarding the location and magnitude of extracranial and intracerebral arterial disease, does not coincide with existing classifications in Europe, and characterizes a hemispheric entity only, as opposed to a global description including prior symptoms in both hemispheres. A new classification system (CHAT) has been designed to deal with these problems, including the current clinical presentation, historical clinical episodes, the site and pathologic type of arterial disease, and information regarding abnormalities of the brain. Using this system, a retrospective review of 480 consecutive carotid endarterectomies is presented, demonstrating the advantages of the CHAT classification. Data include a significant difference in the probability of survival after carotid endarterectomy for asymptomatic stenosis in patients with prior symptoms on the opposite side, as well as a significant difference in the probability of stroke-free survival between patients with amaurosis fugax and those with prior carotid cortical symptoms (TIAs) as the presenting clinical condition. The CHAT classification is suggested as a significant advance in the reporting of all surgical cerebrovascular disease experience, and has particular implications for the current randomized trials between medical and surgical therapy for carotid artery disease.

Actuarial Analysis↗

31P nuclear magnetic resonance of rat pancreatic grafts.

This study investigates whether phosphate metabolite concentrations and intracellular pH alter in early acute rejection of rat pancreatic allografts. In vitro biochemical assays, in vitro 31P nuclear magnetic resonance spectroscopy, and in vivo 31P NMR spectroscopy of the grafts were compared. Duct-ligated, vascularized rat pancreatic isografts and allografts were transplanted onto the infrarenal aorta of the recipients with inferior vena cava venous drainage. In order to obtain reproducible acute rejection, allografting was performed across a major histocompatibility barrier. For the in vitro experiments freeze-clamped graft extracts were prepared and analyzed for adenosine triphosphate concentration by fluorimetry, then placed in an 8.5 Tesla vertical bore magnet. 31P NMR spectra were recorded using a Bruker AM 360 spectrometer operating at 145.7 MHz for 31P. Spectra were acquired from nontransplanted controls; 3-day, 5-day, and 1-month posttransplant isografts, and 3-day and 5-day posttransplant allografts. All grafts examined were functioning satisfactorily. The ATP content of the extracts was significantly lower in the 3- and 5-day allografts than the respective isografts. Invasive in vivo 31P NMR spectra were recorded using surface coils adjacent to the grafts from functioning 5-day posttransplant isografts and allografts (i.e., 3 days prior to an expected elevation in blood sugar from acute rejection in the allografts). The ATP/inorganic phosphate ratios and pH from the in vivo spectra were significantly lower in the allografts than in the isografts. It is concluded that changes in intracellular metabolism occur early in the process of acute rejection and that 31P NMR spectroscopy may provide a means of diagnosing this before current methods.

Adenosine Triphosphate↗

Modified plasma-derived lipoproteins in human atherosclerotic plaques.

Low density lipoproteins extracted from surgical specimens of human atherosclerotic plaques (A-LDL) showed altered electrophoretic mobility indicating a greater negative charge than that of plasma LDL (P-LDL). A-LDL but not P-LDL showed high affinity binding/degradation by human monocyte-derived macrophages; this was inhibited by acetylated LDL but not by native P-LDL. Following injection of 125I-labelled autologous P-LDL prior to reconstructive arterial surgery, polyacrylamide and agarose gel electrophoresis of A-LDL extracted from arterial intima showed that the A-LDL and its apolipoprotein B moiety were derived from P-LDL; the electrophoretic mobility of the product A-LDL was greater than that of native P-LDL. The compositions of arterial intermediate density lipoprotein (A-IDL) and A-LDL differed from those obtained from human plasma intermediate density lipoprotein (P-IDL) and P-LDL. A-IDL showed a reduced triglyceride content and increased esterified and unesterified cholesterol. Although the total cholesterol content of A-LDL was similar to that of P-LDL, there was an increase in unesterified cholesterol and a decrease of cholesteryl ester. These studies indicate that LDL extracted from human atherosclerotic plaque is derived from and modified from P-LDL in vivo. Compared with native P-LDL, A-LDL showed differences in charge and composition, associated with its high affinity binding by the acetyl LDL receptor of human macrophages.

Arteriosclerosis↗

The effect of cigarette smoke, nicotine, and carbon monoxide on the permeability of the arterial wall.

The association between cigarette smoking and the development of atherosclerosis is well established, but the mechanism that makes cigarettes such a potent "risk factor" is not understood. There is normally a constant insudation of plasma macromolecules into the arterial wall. Fibrinogen and lipids are two of the large molecules involved in atherosclerosis. Therefore we studied the effect of cigarette smoke, nicotine, and carbon monoxide on the permeability of the canine arterial wall to 125I-labeled fibrinogen. The results show that inhaled cigarette smoke significantly and rapidly increases the permeability of the arterial wall to fibrinogen and that this effect can be produced with carbon monoxide alone but not with intravenous nicotine.

Animals↗

Transcranial Doppler assessment of cerebral collateral during carotid endarterectomy.

Sixteen patients (mean age 59 +/- 9 years) who were to undergo carotid endarterectomy were examined pre- and peroperatively using pulsed Doppler-shifted ultrasound; blood velocities in the middle cerebral artery were measured before and during common carotid compression in the conscious patient, and before and during measurement of carotid stump pressures at surgery in the anaesthetized patient. Measurements at endarterectomy showed a significant difference in middle cerebral artery blood velocities from patients with stump pressures of greater and less than 50 mmHg (t = 4.0, P less than 0.005). A threshold of 10 cm s-1 distinguished between stump pressures of greater and less than 50 mmHg in 15 of the 16 patients. Pre-operative blood velocity measurements during carotid compression did not correlate with those taken peroperatively at carotid clamping.

Adult↗

Early diagnosis of femorodistal graft stenoses.

Detection and early correction of stenoses following femorodistal bypass grafting may prevent graft occlusion. We studied 43 grafts (36 saphenous vein and 7 human umbilical vein) prospectively by peroperative angiography and then by clinical assessment, post-exercise Doppler ankle pressures and digital subtraction angiography at 1 week, 3 months, 6 months and 1 year. There were 11 grafts inserted for critical ischaemia, 16 for rest pain and 16 for disabling claudication. Four patients died within the year with five patient grafts and these were excluded from the final results. Eight grafts failed during the first year; four within 1 month and a further four subsequently, with no warning alteration of symptoms, ankle Doppler pressure or digital subtraction angiography. Four additional grafts were jeopardized by symptomatic stenoses. Six grafts developed an asymptomatic stenosis of greater than 50 per cent without a change in exercising ankle Doppler pressure. Three symptomatic stenoses were successfully revised but the fourth occluded on conservative management. Three asymptomatic stenoses have also been successfully revised and three have been treated conservatively. Close surveillance of femorodistal grafts is justified by this study but a deterioration in ankle brachial Doppler index was only useful in the patients with recurrent symptoms and was unable to detect half the stenoses of greater than 50 per cent. The detection of these by intravenous digital subtraction angiography might help to avoid graft failure.

Adult↗

Reduced response of cerebral blood flow to hypercapnia: restoration by extracranial-intracranial bypass.

Cerebral blood flow, estimated by the xenon clearance technique, has been used to study eight patients before and after extracranial-intracranial (EC-IC) bypass surgery. Response of cerebral blood flow to hypercapnia was also measured to estimate cerebral reactivity, an indicator of cerebral vasodilator reserve capacity. Measurements in all patients were repeated 3 months after surgery. Resting cerebral blood flow was not increased by the operation but cerebral reactivity in the ipsilateral hemisphere was significantly increased in all patients (P = 0.002). Reactivity also increased in the contralateral hemisphere in six of the eight patients (P = 0.065). The response of cerebral blood flow to hypercapnia may prove useful in the selection of symptomatic patients with carotid occlusions or inaccessible stenoses for revascularization by EC-IC bypass.

Aged↗

Effect of carotid endarterectomy on cerebral blood flow and its response to hypercapnia.

Cerebral blood flow (CBF) was measured in 14 patients before carotid endarterectomy, 3 h after surgery and 2 days postoperatively using the intravenous xenon-133 technique. In 11 of the patients CBF was remeasured at 6 months and in 8 patients CBF and the response to hypercapnia (5 per cent CO2 in air) was measured pre-operatively and 6 months following surgery. All operations were performed using an intraluminal Javid shunt and internal carotid artery (ICA) 'stump' pressure was recorded. CBF measured at 3 h after endarterectomy revealed a postoperative cerebral hyperperfusion with significantly increased flows in both hemispheres. There was a significant correlation between carotid cross clamping time and ipsilateral hemispheric CBF increase which implied an ischaemic aetiology for the hyperperfusion and supported the routine use of an intraluminal shunt in carotid endarterectomy. Six months after surgery, CBF had returned to its preoperative value but reactivity to CO2 was significantly improved, which suggested that the operation had increased cerebral reserve.

Aged↗

Evaluation of a new classification of cerebrovascular disease: CHAT.

A new scheme that classifies cerebrovascular disease on the basis of current and prior clinical symptoms, arteriographic findings, and target organ abnormalities has been evaluated. The scheme proved to be easy to learn and to use. Its utility was demonstrated by the previously unreported distinctions that became apparent when various patient subsets were analyzed according to the CHAT classification. These included an improved probability of stroke-free survival in patients operated on for brief strokes (transient ischemic attack) as opposed to temporary strokes (reversible ischemic neurologic deficit), and similarly improved survival probability in patients operated on for amaurosis fugax in comparison to those with carotid territory hemispheric transient ischemic attacks. The impact of multiple arterial lesions and positive computerized tomography scan findings appeared to be minimal with respect to both late stroke and survival in our preliminary observations. The simplicity and utility of the CHAT scheme make it a useful method to evaluate and report clinical experience with cerebrovascular disease.

Carotid Arteries↗

A method for quantifying lipoprotein flux rates between plasma and arterial intima in vivo.

A new method is proposed for measuring in vivo the rates of transfer of plasma lipoprotein into and out of arterial intima in man. The technique requires the injection of a lipoprotein which can be labelled with two different tracers, followed by a single arterial sample during elective surgery. The feasibility of the method was tested by computer simulation and it was found that measurement uncertainties of the order of those likely in practice produced uncertainties of 7% SD in the calculated influx and 16% SD in the calculated efflux rates. The principal assumption, that lipoprotein in arterial intima can be modelled as a single compartment system, was tested in a preliminary study in an anaesthetised dog: reasonable evidence of monocompartmental behaviour was obtained. The new method was used in a preliminary study of three patients undergoing elective arterial surgery. Low density lipoprotein (LDL) labelled with 125I was injected about 24 h before surgery, followed by 131I-labelled LDL 4 to 6 h before surgery. The radioactivities of washed extracts of arterial intima were then measured in a gamma counter. LDL flux rates were higher in atherosclerotic specimens than in less seriously diseased or normal tissue, and were highest in the most hyperlipidaemic patient.

Animals↗