N. L. Browse

Pericapillary fibrin in the ulcer-bearing skin of the leg: the cause of lipodermatosclerosis and venous ulceration.

Forty-one biopsy specimens, taken from the ulcer-bearing skin of 41 legs of 21 patients attending the varicose vein clinic, were selectively stained for fibrin with phosphotungstic acid haemotoxylin before being blindly assessed,. Layers of fibrin were found surrounding the dermal capillaries in all 26 legs with lipodermatosclerosis. None of the specimens from the 15 legs with clinically normal skin contained fibrin. There was also an increased number of dermal capillaries cut in cross section per high powered field in 24 of the 26 legs with lipodermatosclerosis compared with two of the 15 legs with normal skin (p less than 0.001). The mean reduction in foot vein pressure during exercise was significantly less in the 26 limbs with pericapillary fibrin than in the other 15 limbs (p less than 10(-6). Lipodermatosclerosis is synonymous with pericapillary fibrin deposition and is associated with, and probably secondary to, both a persistently raised venous pressure and an increase in the size of the dermal capillary bed. This extravascular deposition of fibrin probably stimulates tissue fibrosis and blocks the diffusion of oxygen to the overlying epidermis, producing cellular death and venous ulceration.

Comparison of venous reflux assessed by duplex scanning and descending phlebography in chronic venous disease

Venous reflux was assessed by duplex scanning and descending phlebography in 98 limbs of 52 patients. There was moderately good agreement for deep vein reflux elicited by a standardised Valsalva manoeuvre, classified by a modified Kistner grading (0 to IV). The same grade was found in 58 limbs, with a difference of one grade in 27 limbs, and more than one grade in 13. Descending phlebography underestimated reflux in the lower leg compared with duplex scanning. The presence of reflux found on duplex scan correlated with the half-volume refilling time on a foot-volume plethysmogram with a below-knee tourniquet. There was no correlation between descending phlebography and the half-refilling time. Ascending phlebography showed post-thrombotic changes in 23 limbs. The duplex scan confirmed severe reflux (grades III and IV) in 14 of these 23 limbs, and demonstrated isolated reflux below normal valves in 4 other limbs. Severe reflux was seen on the descending phlebogram in only 10 of the 23 limbs with post-thrombotic changes. Duplex scanning may be a better method for detecting reflux than descending phlebography and is more acceptable to the patient. Ascending phlebography remains essential to display anatomical abnormalities found in some postthrombotic limbs that are not associated with reflux.

Streptokinase and deep vein thrombosis.

Five patients with deep vein thrombosis were given streptokinase. Five others with similar phlebograms were given anticoagulants, and the results assessed by examining changes in the iliac, femoral, and calf segments of the phlebograms when repeated 7-10 days later. Those of the anticoagulant group were unchanged. Four of the five given streptokinase had a reduction in the size and extent of their thrombosis. Fresh thrombus surrounded by flowing blood was lysed. Thrombus completely blocking a vein was not lysed. The indications for the use of streptokinase in deep vein thrombosis are reviewed.

Oxidisability of low density lipoproteins in patients with carotid or femoral artery atherosclerosis

Oxidation of low density lipoprotein (LDL) is implicated in the pathogenesis of atherosclerosis. In this study the susceptibility to oxidation of LDL (from patients with atherosclerosis) is related to the progression of the disease. LDL were isolated from 37 patients with demonstrable atherosclerotic plaques. The susceptibility of LDL to oxidation (induced by an exogenous oxidative stress) was assessed by measuring the breakdown products of lipid peroxidation, the increased formation of conjugated dienes, and changes in surface charge of the apolipoprotein B (apo B). Progression of the atherosclerotic plaque was assessed by measuring the maximum velocity of blood through the narrowest portion of the vessel at inclusion and after one year. Twenty-nine of the 37 samples taken were found to have LDL that were partially oxidised, whereas 8 samples showed LDL whose state of oxidation was within the normal range. Progression of the atherosclerotic plaque occurred in 19 (66%) of the 29 patients whose lipoproteins were partially oxidised compared with only 2 (25%) of the 8 patients with normal lipoproteins (P = 0.055, Fishers exact test). These data support an association between the progression of atherosclerotic plaques in carotid and femoral vessels and the susceptibility to oxidation of LDL.

Comparison between Sequelae of Surgical and Medical Treatment of Venous Thromboembolism

Thirty-six patients have been studied clinically and phlebographically three years after a major deep vein thrombosis. Twenty were treated surgically and 16 medically. The incidence of post-thrombotic symptoms was similar in the two groups. The use of superficial femoral vein ligation to prevent embolism will not worsen the prognosis of a leg which is already the site of deep vein thrombosis.

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.

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.