Asymptomatic carotid murmur: ultrasonic factors influencing outcome.

Sixty consecutive patients with an asymptomatic mid-cervical murmur on auscultation were identified amongst 1000 patients who underwent duplex scanning of the extracranial carotid arteries during 1981-83. They were classified according to the scan results into 12 high risk subjects with greater than 75 per cent stenosis of an internal carotid artery, 37 low risk subjects with a less than 75 per cent stenosis and 6 with no detectable stenosis. The mean duration of follow-up was 3 years (minimum 2 years) or until stroke or death. One was lost to follow-up and four were excluded having undergone carotid endarterectomy during the study. Six of twelve subjects with greater than 75 per cent stenosis suffered a stroke (five fatal and one non-fatal). There were no premonitory signs except in one patient with non-focal cerebral ischaemia for 2 months before an hemispheric stroke. There was one fatal stroke in the less than 75 per cent stenosis group and none in the control group. In all, 17 (28 per cent) patients died (myocardial infarction, 8; stroke, 6; malignant disease, 3). These results confirm that asymptomatic carotid murmurs are associated with increased mortality with most having non-severe carotid disease on duplex scanning and few strokes during follow-up. There is an important minority with tight carotid stenosis who carry a worrying risk of stroke if left untreated.

Compliance changes in in-situ femoropopliteal bypass vein grafts.

Changes in wall structure, including neo-intimal proliferation and medial fibrosis, have been implicated as a cause of late occlusion in reversed femoropopliteal vein grafts. These changes can be measured indirectly as a fall in compliance. It has been suggested that long-term patency might be improved by the in situ technique because the nutrient vasa vasorum are left intact and therefore wall structure preserved. We have measured the compliance of 62 in situ vein grafts, with times after operation ranging from 2 days to 6 years, and also compared the compliance changes, in the first 3 months after operation, of 15 undisturbed in situ vein grafts with 15 fully mobilized in situ vein grafts. Compliance was derived non-invasively from the pulse wave velocity using Doppler ultrasound. There was a significant fall in compliance after operation (P less than 0.001) and no difference could be found between the undisturbed and mobilized in situ vein grafts (P greater than 0.1). Histological examination of 6 grafts suggested that the fall in compliance was due to neo-intimal proliferation which still occurred although medial fibrosis was reduced. Any potential improvement in long-term patency rates using the in situ technique must be due to other factors.

Correlation of clinical findings, duplex carotid artery scanning and CT scanning of the brain in 54 consecutive patients with bruits over the carotid artery bifurcation.

Fifty-four patients presenting consecutively with bruits over the carotid artery bifurcation have been studied by Duplex ultrasonography of the carotid artery and CT of the brain. The patients were divided into symptomatic (transient ischaemic attacks (TIA), non-focal neurological symptoms, minor and major strokes) and asymptomatic groups. The duplex scans were subdivided into those showing a greater than 50% stenosis of the internal carotid artery and those with a less than 50% stenosis. The CT brain scans were subdivided into those showing evidence of cerebral infarction and those without. Symptomatic patients were found to be more likely to have an area of cerebral infarction than asymptomatic ones (P = 0.0086 Fisher's Exact Test). Patients with a significant stenosis (greater than 50%) of the internal carotid artery were more likely to have an ipsilateral cerebral infarction on CT than patients with a minor stenosis (less than 50% stenosis) (P = 0.028 Fisher's Exact Test). Three patients (two with TIA's and one with non-focal neurological symptoms) were found to have unsuspected cerebral infarcts on CT of the brain. These patients could theoretically be at risk following carotid endarterectomy and revascularization if the infarct were an early one. Patients with non-focal neurological symptoms and carotid bruit were more likely to have a significant stenosis than asymptomatic patients with carotid bruit (P = 0.0069 Fisher's Exact Test). Therapy should be directed at the carotid artery lesion in these cases. Duplex scanning of the carotid artery bifurcation may be combined usefully with CT brain scanning in the non-invasive investigation of patients with symptomatic extracranial carotid artery bruits.

Structure-activity studies on phosphonoacetate.

Phosphonoacetic acid is a selective antiherpesvirus agent. More than 100 congeners of phosphonoacetic acid were evaluated in vitro and in vivo to understand structure-activity relationships in the hope of designing a superior analog. Results showed that the antiherpesvirus activity had highly specific structural requirements. Neither the carboxylic nor the phosphono groups could be replaced. The distance between these two groups is important. Increase of this distance caused complete loss of activity. However, if this distance was maintained, the addition of groups to the methylene carbon resulted in a reduction, but not loss, of activity. On the other hand, decrease of the carbon chain to formic acid did not deteriorate its antiherpes activity. All analogs tested had lower activity than the parent compound. However, some compounds with decreased activity in vitro appeared to have favorable pharmacological properties in vivo.

In situ femoropopliteal and distal vein bypass for limb salvage--experience of 50 cases.

The aim of this paper is to assess the in situ technique of saphenous vein femoropopliteal (and femorotibial) bypass for limb salvage, and to compare it with the reversed vein method of bypass. In our 3-year study, we have operated on 50 cases resulting in a graft patency and limb salvage rate of 78 per cent at 18 months and 72 per cent overall. There was a 2 per cent perioperative and 10 per cent overall mortality. Graft thrombosis was associated with a variety of factors, mostly notably a small vein (les than 4 mm), a low calf vessel anastomosis, wound sepsis and progressive proximal (inflow) disease. However, the strongest correlation was that between graft thrombosis and the extent of distal disease, as 11 of 12 cases with thrombosed grafts had grade 2 or 3 run-off. In our experience the in situ technique offers haemodynamic and technical advantages over the reversed vein method of performing straightforward femoropopliteal bypass. Moreover, the in situ technique has wider application in that it allows a smaller vein (greater than 2.5 mm) to be used and also makes anastomosis to a small calf vessel easier. In this series, 16 per cent of cases would have been considered unsuitable for the reversed vein method if 4 mm was accepted as the lower limit of size for a reversed vein graft.

Synthesis and anti-herpes simplex activity of analogues of phosphonoacetic acid.

The synthesis of monoesters (P and C) of phosphonoacetic acid (PA) is given. The carboxyl esters were prepared by two methods: the reaction of chloroacetates with tris(trimethylsilyl) phosphite, followed by hydrolysis; and by the acid-catalyzed esterification of PA with the appropriate alcohol. P-Monoesters of PA were prepared either by the reaction of alkyl[bis(trimethylsilyl)] phosphite with benzyl chloroacetate followed by deprotection or by the reaction of dimethylphenyl phosphite with benzyl bromoacetate followed by hydrogenolysis. Three aryl- (alkyl-)phosphinic acid derivatives are reported. The above compounds were evaluated for anti-herpes activity against HSV-induced DNA polymerase and in animals infected with herpes dermatitis.