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Biomedical subjects

N L Browse

Publications and source records attributed to N L Browse.

At least 19 recordsLinked to original sources

Lymphangiomatosis of the limbs. Clinicopathologic analysis of a series with a good prognosis.

Six cases of a distinctive but poorly recognized variant of lymphangiomatosis with predominant or exclusive involvement of the soft tissues of the limb/limb girdle are described. The six patients were male and presented with slowly progressive swelling of the involved limb. The age of onset was at birth (three cases), 3 months (one case), 11 years (one case) and 12 years (one case). Five patients had involvement of the lower extremity and one of the right upper extremity. Three patients had concomitant asymptomatic bone involvement either in the affected limb (two cases) or in distant bones (one case). Only one patient had visceral involvement that was limited to the ipsilateral thorax and was associated with chylothorax. Diagnosis was confirmed in all but one patient by lymphangiography. Treatment consisted principally of surgical reduction with significant clinical improvement. No patient later developed systemic involvement and the clinical course was benign. The bone lesions did not progress in any patient. Histologically, each case was characterised by interconnecting, dilated lymphatic spaces, lined by a single, attenuated layer of endothelial cells, involving the dermis, subcutis, and occasionally, underlying fascia and skeletal muscle with characteristic and extensive "dissection" of collagen and surrounding normal adnexal structures. Despite the absence of red blood cells in the vascular spaces, interstitial hemosiderin deposition was prominent in four cases. As opposed to most cases of lymphangiomatosis, which usually have extensive visceral involvement associated with a very poor prognosis, involvement in this variant is limited almost exclusively to soft tissues of the limb and bone and is associated with good prognosis.

Arm

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.

Adult

Effect of foot compression on the velocity and volume of blood flow in the deep veins.

The A-V Impulse System reduces the incidence of deep vein thrombosis by pneumatically compressing the venae comitantes of the lateral plantar artery, causing an increase in the velocity of blood in the proximal axial veins. Using a duplex scanner the effects of altering the pressure, pulse duration and frequency of foot compression on the velocity and volume of blood flow in the superficial femoral and popliteal veins were quantified. In 20 legs, foot compression of 50, 125 and 200 mmHg significantly increased the maximum venous blood flow by 9.0, 13.4 and 15.1 ml/s respectively (P < 0.001). Conversely, reducing the frequency of compression from 6 to 3 cycles per min significantly increased the rise in peak flow from 10.1 to 14.8 ml/s (P < 0.001). Changing the duration of compression from 1 to 3 s had no significant effect on peak flow. Increased blood flow is best achieved with high-pressure low-frequency foot compression. Increasing the duration of compression beyond 1 s has no effect on augmentation of flow in the deep veins.

Adult

Use of Teflon stents for lymphovenous anastomosis.

The treatment of lymphoedema is difficult; conservative and surgical management show variable results. Lymphovenous anastomoses (LVAs) in experimental animals and patients give poor results in the treatment of primary lymphoedema and variable results in that of secondary lymphoedema. Conventional sutured LVAs were compared with anastomoses using polytetrafluoroethylene (Teflon) stents; 32 sutured and 21 stented LVAs were constructed in 16 rabbits with normal lymphatics. Anastomoses were assessed for quality and patency at 1-16 weeks by direct exposure; 27 cases were further assessed using lymphangiography. Patency in stented and sutured LVAs was 71 and 38 per cent at 1 week, and 38 and 8 per cent at 3 weeks, respectively. After 4 weeks all anastomoses were occluded. The quality of stented LVAs seemed to be higher than that of sutured LVAs. Stented LVAs are feasible and probably superior to conventional sutured LVAs. However, the patency of LVAs is of short duration because of the disadvantageous pressure gradient from lymphatics to veins, and this limits their clinical application.

Anastomosis, Surgical

Aetiology and treatment of chylous ascites.

A series of 45 patients with chylous ascites has been reviewed. The age at presentation ranged from 1 to 80 (median 12) years; 23 patients were aged < or = 15 years. Thirty-five patients had an abnormality of the lymphatics (primary chylous ascites); in the remaining ten, the ascites was secondary to other conditions, principally non-Hodgkin's lymphoma (six patients). Two principal mechanisms of ascites formation were identified using lymphangiography and inspection at laparotomy: leakage from retroperitoneal megalymphatics, usually through a visible lymphoperitoneal fistula (14 patients); and leakage from dilated subserosal lymphatics of the small intestine, invariably associated with leaking lacteals causing protein-losing enteropathy (24 patients). Both sites of leakage were present in a further five patients. In the remaining two patients, chyle was leaking from normal mesenteric lymphatics, in one via a ruptured mesenteric lymph cyst and in the other from the site of a previous lymph node biopsy. Other associated lymphatic abnormalities were present in 36 patients, lymphoedema of the leg being the commonest (26 patients). All patients were initially treated conservatively with dietary manipulation; this was the most satisfactory treatment for those with leaking small bowel lymphatics. Surgery (fistula closure, bowel resection or insertion of a peritoneovenous shunt) was performed in 30 patients. Closure of a retroperitoneal fistula, when present, was the most successful operation, curing seven of the 12 patients so treated.

Adolescent

Repair and replacement of deep vein valves in the treatment of venous insufficiency.

Venous insufficiency is a widespread condition, the prevalence of venous ulceration being 0.5-1.0 per cent in Western populations. A principal abnormality causing venous insufficiency is deep venous reflux, usually resulting from post-thrombotic valve destruction. Patients undergoing treatment for venous insufficiency should have all venous abnormalities investigated, defined and corrected where possible. Although treatment for superficial and communicating vein incompetence is available, correction of deep vein reflux has been neglected until recently. Deep vein valve physiology, the selection of patients for deep vein valve surgery and methods of valve repair and replacement are reviewed.

Animals

In situ venous valve construction.

A technique of in situ deep venous valve construction based on vein wall intussusception is described. The technique has been used to construct a size-matched, autogenous valve in the femoral vein of the dog. Forty-one valves have been constructed. Immediately after construction, all 41 were patent at ascending phlebography and Harvey's test showed them to be competent. Descending phlebography demonstrated competence in 38 valves. Hydrostatic testing was performed on 27 valves in the vertical position at pressure gradients in the range 0.2-250 cmH2O. Of these, 24 valves were fully competent. Six valves were studied at intervals between 1 and 112 days after construction. All six were competent by Harvey's test and five were competent at descending phlebography. There was no evidence of thrombosis in any valve. This technique may be suitable for replacement of deep venous valves in patients with the calf pump failure syndrome caused by deep venous reflux.

Animals

Fibrinolytic activity of the arms and legs of patients with lower limb venous disease.

Clearance of subcutaneous 125I-labelled fibrin was prolonged from the legs but not from the arms of patients with uncomplicated varicose veins and patients with healed ulcers, compared with controls. The euglobulin clot lysis time (ECLT) of blood from the arms and legs of those with healed ulcers was prolonged; venous congestion significantly shortened the ECLT of blood from all limbs except legs with healed ulcers. The clearance of interstitial fibrin of both legs and arms correlated with the response of the ECLT to venous congestion (P less than 0.05). The clearance of interstitial 125I-labelled albumin in five patients with healed ulcers was faster from the legs than from the arms, whereas the clearance of interstitial 125I-labelled fibrin was faster from the arms in all cases. These results suggest that there is a defect in interstitial fibrinolytic activity as well as vein wall production of plasminogen activator in legs with chronic venous insufficiency.

Arm

Fibrinolytic activity and calf pump failure.

The interstitial fibrinolytic activity of the upper and lower limbs was investigated in subjects with abnormal calf pump function by measuring the lysis rate of experimentally produced subcutaneous 125I-fibrin clots. Thirty-three subjects with healed venous ulcers, five with varicose veins and 11 controls were studied. 125I-fibrin clots were produced in the subcutaneous tissue of the forearms and legs and clearance half-life was calculated. Calf pump function was assessed by foot volumetry and the 'gaiter' skin nutritive circulation by measuring the transcutaneous oxygen tension (PtcO2). Fibrin clearance was prolonged from the subcutaneous tissues of the legs of subjects with varicose veins and healed ulcers compared with controls. Negative correlations were found between fibrin clearance half-life and the half-volume refilling time (P less than 0.01) and the PtcO2 (P less than 0.01).

Fibrinolysis

Measurement of the healing of venous ulcers.

The surface area of 99 leg ulcers was measured from a scaled photograph using a computerized ultrasonic digitizer. This was compared with the area obtained by multiplying the two maximal perpendicular diameters of each ulcer. There was an extremely good correlation between these two methods (r = 0.951). Seventy-four patients were followed up as part of a placebo-controlled double-blind study. In this study, treatment was assessed by the time taken for the ulcerated limb to heal completely. The initial ulcer size was found to be a weak predictor of subsequent ulcer healing (r = 0.49). The healing rates of individual ulcers calculated over 1 month intervals from presentation proved to be a poor predictor of the time required for complete ulcer healing (Spearman rank correlation coefficients ranged from 0.15 to 0.61). The healing curves of individual ulcers showed considerable fluctuations during the process of healing. The product of the maximal dimensions of an ulcer provides an easy and accurate method of monitoring treatment. The reduction in ulcer size within a set time interval, used in many ulcer studies, is a poor predictor of eventual ulcer healing. The percentage of ulcers completely healed within a pre-determined time interval is a better method of assessing new treatments.

Adult

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