Spontaneous fulminant gas gangrene.

Gas gangrene is a rare condition, usually associated with contaminated traumatic injuries. It carries a high rate of mortality and morbidity. A number of studies have implicated non-traumatic gas gangrene and colonic neoplasia. This paper reports a patient who presented spontaneously with Clostridium septicum gas gangrene and an occult caecal carcinoma.

Forearm blood flow measurements using technetium-99m human serum albumin following brachial arteriotomy.

A simple, low cost method for measuring forearm blood flow during reactive hyperemia has been developed. Subjects are seated with hands and forearms over a large field-of-view gamma camera. Blood pressure cuffs inflated above the elbows isolate the blood in the forearms and hands and induce a hyperemic response. The remaining blood pool is labeled with technetium. The rate of increase of activity following release of the cuffs is measured from the gradient of time-activity curves and is calibrated for flow by counting a venous blood sample. The technique has been applied to a group of normal controls and to symptomatic and asymptomatic patients following right brachial arteriotomy. Forearm blood flow in normal subjects was 32.9 +/- 6.4 ml/100 ml/min and for subjects with occlusion of the brachial artery was 6.4 +/- 2.1 ml/100 ml/min. The method is simple, widely available, and reproducible. The good signal to noise ratio allows it to be used in cases of very low flow either as an aid to diagnosis or to measure treatment response.

Results of vascular reconstruction with double velour Dacron in patients with critical lower limb ischaemia.

The results of 65 arterial reconstructions with double velour Dacron carried out for limb salvage have been reviewed. Successful revascularization was achieved initially in 86%, and the peri-operative mortality was 9.0%. Cumulative salvage was greater in patients with aorto-iliac disease (65% at 5 years) than in those with femoropopliteal disease (36% at 5 years). Results were poorest in patients with gangrene or marked trophic changes at presentation, in those with distal disease and in those who required revisional surgery.

Comparison of the thrombogenicity of four types of knitted Dacron arterial graft in an artificial circulation.

The thrombogenicity of four types of knitted Dacron arterial graft was compared by measuring the effect of each prosthetic graft on human platelet function in an artificial circulation. The grafts examined were plain knitted (Meadox 'Cooley'), knitted double velour (Meadox 'Microvel'), filamentous external velour (U.S.C.I. 'Sauvage Filamentous') and a plain knitted graft with a pyrolytic carbon coating (Meadox 'Carboknit'). Platelet count, adhesion and percentage aggregation were all decreased during perfusion. The greatest changes in these parameters were produced by the filamentous velour graft and the least by the carbon coated graft. Electron microscopy demonstrated significantly more platelets adherent to the filamentous graft (rho less than 0.01) with changes in platelet morphology indicating activation. These results suggest that the filamentous graft is more thrombogenic than the other grafts.

Effect of preclotting on the porosity and thrombogenicity of knitted Dacron grafts.

The effects of single- and four-stage preclotting methods on graft porosity and thrombogenicity were compared in two types of Dacron prosthesis. The single-stage method significantly reduced leakage of blood (P less than 0.001), but did not seal the grafts. The four-stage method rendered the grafts impermeable at the second step. Thrombogenicity was compared by perfusing preclotted grafts with fresh heparinized blood (containing 111In-labelled platelets) in an artificial circulation. Platelet deposition and consumption were significantly less in the four-stage method whilst platelet function remained unchanged during perfusion. We conclude that the four-stage technique is superior to standard preclotting methods by rendering knitted Dacron grafts impermeable and hypothrombogenic.

The distribution of plasminogen activator in the male genital tract.

The distribution of fibrinolytic activity in the tissues of the male genital tract was studied by a histological technique. Preparations made from testis, epididymis, vas deferens, seminal vesicle, prostate, bulbo-urethral gland, and urethra showed that most activity was related to the blood vessels. However, inconsistent fibrinolytic activity related to epithelium was found in all parts of the genital tract. This epithelial activity was least in the testis, greater in the seminal vesicle and prostate gland, and was greatest in the bulbo-urethral gland and terminal urethra. No fibrinolytic activity could be demonstrated in relation to spermatozoa.

Plasminogen activator in the human prostate.

The distribution of plasminogen activator in fresh human prostatic tissue has been studied, using a histological technique. The vascular endothelium consistently showed fibrinolytic activity while inconstant and lesser activity arose from the epithelial cells of glands and ducts. Increased epithelial activity was often accompanied by evidence of trauma. Activity of the secretions was insignificant. The source of the fibrinolytic activity of blood in prostatic disease and of the seminal fluid remains uncertain, and cannot yet be ascribed to the prostatic epithelium.

The clinical application of forearm and hand blood flow measurements using a gamma camera.

A new method of measuring blood flow to forearms and hands during reactive hyperemia is described. Subjects are positioned with forearms and hands over a gamma camera, and the circulation below the elbows is isolated for 4 minutes with pneumatic cuffs. The remaining blood pool is labeled with technetium-99m-labeled human serum albumin given via a vein in the dorsum of the foot. The rate of rise of activity in the arms after cuff release is measured from the gradient of time activity curves, and these are calibrated for flow by counting a sample of venous blood. Blood flow per unit volume is obtained from measurements of the limb volume, done by water displacement. Results for eight normal control subjects showed a mean flow per unit volume to forearm plus hand of 32.9 +/- 6.4 ml/100 ml/min and to hand alone 36.5 +/- 6.9 ml/100 ml/min. Case studies of patients with a variety of large- and small-vessel diseases are presented, illustrating the use of the technique to aid diagnosis and measure response to treatment.

Antithrombotic therapy for vascular prosthesis: an experimental model testing platelet inhibitory drugs.

Although Dacron vascular grafts are widely used, they are thrombogenic and rapid blood flow maintains patency. When blood flow is suboptimal, antithrombotic therapy may prevent early occlusion. We evaluated the effect of three platelet inhibitory drugs: acetylsalicylic acid (ASA), dipyridamole (DPM), sulphinpyrazone (SPZ), and a combination of ASA plus DPM on platelet adherence to woven Dacron in an artificial circulation. Heparinized blood from 18 volunteers was divided equally for test and control circuits, and to the test each drug was added in therapeutic concentration. The experiment was repeated ex vivo using blood donated by six volunteers after each had taken, separately for 1 week: (1) no drug; (2) ASA, 300 mg, three times a day; (3) DPM, 100 mg, four times a day; (4) SPZ, 200 mg, four times a day; (5) ASA, 300 mg, plus DPM, 75 mg, combined, three times a day. Platelet count, adhesion and aggregation were measured during the 60-minute perfusion, and scanning electron miscroscopy of the graft's luminal surface was performed. ASA was the most effective single agent, significantly impairing platelet function and reducing consumption of platelets by the graft. DPM reduced platelet adherence only in the ex vivo experiment, and its addition to ASA imparted no further influence. Sulphinpyrazone had little effect in either experiment. Antithrombotic therapy with ASA and DPM requires clinical evaluation.

Modulation of 5-HT receptor subtype-mediated behaviours by corticosterone.

Malfunction of the serotonergic system and dysregulation of the hypothalamo-pituitary-adrenocortical axis have been implicated in the pathophysiology of depression. Several studies provide evidence for reciprocal influences between glucocorticoids and 5-HT receptors. The effect of repeated treatment with a high dose of corticosterone (50 mg/kg s.c. twice daily for 4 days) on 5-HT receptor subtype-mediated behaviours was studied. It was found that in rats that were repeatedly treated with corticosterone the number of 2-chloro-6-(1-piperazinyl)pyrazine HCl (MK 212)-induced, 5-HT2C receptor-mediated penile erections were reduced, whereas both MK 212 and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced 5-HT2A receptor-mediated head shakes were increased. The (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced lower lip retraction mediated by presynaptic 5-HT1A receptors was unchanged, whereas the open field activity induced by 8-OH-DPAT was enhanced in corticosterone pretreated rats. These changes in 5-HT receptor subtype-mediated behaviours were not seen after a single injection with corticosterone given 24 h or 5 days before. The results suggest that 5-HT2A, 5-HT2C and postsynaptic 5-HT1A receptor-mediated behaviour can be modulated by repeated treatment with a high dose of corticosterone.

Tissue levels of cephradine in ischaemic limbs following a single intravenous injection.

A single dose of 2g cephradine was administered intravenously at the time of anaesthetic induction to 20 patients with occlusive arterial disease. Concentrations of cephradine were measured in serum, subcutaneous fat from the groins of 10 patients underdoing arterial reconstruction and in the subcutaneous fat and skeletal muscle of 10 legs amputated for severe arterial ischaemia. Concentrations of cephradine were adequate for antibacterial prophylaxis at the time of operation in all serum samples, 9 out of 10 samples of subcutaneous fat from reconstruction cases, all muscle and 8 of 10 fat samples from the level of section of amputated limbs, and in 8 of 10 muscle and fat samples from the distal parts of amputated limbs. These results confirm that a single intravenous dose of 2 g cephradine given with anaesthetic provides adequate serum and tissue concentrations for antibacterial prophylaxis during vascular surgery.

Peroperative cephradine concentrations in the gall bladder wall and bile.

Cephradine levels were assayed in serum, gall bladder wall and bile sampled from the gall bladder and common bile duct in 24 patients undergoing elective cholecystectomy. Cephradine was administered either as 1 g given intravenously at the time of anaesthetic induction, or as three 6-hourly doses of 0.5 g taken orally during the pre-operation day followed by 1 g intramuscularly with the premedication. Adequate antibacterial levels of cephradine were achieved in all serum samples, 8 of 9 samples of choledochal bile, 6 of 12 samples of cholecystic bile and all 12 samples of gall bladder wall in the group receiving a single intravenous dose, compared to only 4 of 12 serum samples, 6 of 11 choledochal bile samples, 6 of 10 cholecystic bile samples, and only 3 of 12 samples of gall bladder wall in the group receiving oral cephradine. Therefore, cephradine given as a 1 g bolus intravenously with anaesthetic induction provides satisfactory concentrations for antibacterial prophylaxis during gall bladder surgery but a regimen of oral and intramuscular dosage was found to be unsatisfactory.

The penetrability of cephazolin into the subcutaneous fat and skeletal muscle of ischaemic lower limbs with atherosclerotic disease.

Seventeen patients with atherosclerotic disease, who were undergoing arterial reconstruction or amputation of the lower limb, had 2 g cephazolin injected per-operatively in two equal doses by intramuscular and intravenous routes. Samples of subcutaneous fat and skeletal muscle from the ischaemic leg, and serum were collected during the operation for assay of cephazolin content. The mean cephazolin levels in the serum, skeletal muscle and subcutaneous fat were found to be well above the minimum inhibitory concentrations required for most important Gram-positive and Gram-negative pathogens.

Evaluation of tissue levels of cefamandole in severely ischaemic lower limbs using two regimens of dosage.

Cefamandole levels were measured in peripheral blood, and in skeletal muscle and subcutaneous fat samples taken from 20 patients during amputation of the leg for severe ischemia. Tissue samples were taken from both proximal and distal levels in the amputated limb. Cefamandole was administered as either a 2 g intravenous bolus given with induction of anaesthesia, or a combination of 1 g intramuscularly with the premedication plus 1 g intravenously with anaesthetic induction. Levels of cefamandole in serum and proximal muscle and fat samples were well above the minimum inhibitory concentrations required for most Gram-positive and Gram-negative organisms. Cefamandole levels in more distal samples were somewhat lower but still achieved therapeutic levels in most cases. Higher tissue levels of cefamandole were achieved when 2 g were given intravenously as a bolus.

A study on tissue concentrations of cephradine achieved in patients with peripheral vascular disease.

The levels of cephradine were measured in serum, voluntary muscle and subcutaneous fat samples collected from 30 patients during surgical operations for peripheral vascular disease. Cephradine 2 g was administered in two equal doses by intramuscular and intravenous routes before each operation. The mean levels found in the serum and muscle were well above the minimum inhibitory concentrations required for most important Gram-positive and Gram-negative pathogens, in contrast to the relatively low mean level found in subcutaneous fat.

Does oxpentifylline ('Trental') have a place in the treatment of intermittent claudication?

In a randomized double-blind study, the clinical and haemorrheological responses of 40 patients receiving oxpentifylline (200 mg 3-times daily) were compared with those of 40 patients receiving placebo. The treatment period in both groups was 2 months. The parameters measured before and after treatment were: subjective response; claudication and maximum walking distances; ankle systolic indices; maximum blood flow in the lower limb by gravimetric plethysmography; plasma fibrinogen; erythrocyte deformability and whole blood viscosity. There was a significant increase (p less than 0.05) in mean erythrocyte deformability in the oxpentifylline group but not in the placebo group; this apparent difference between the groups, however, was not significant. The placebo group showed a significant improvement (p less than 0.05) in claudication distance and mean plasma fibrinogen concentration, but no such improvements were observed in the oxpentifylline group. There were no significant differences in either of the two groups with regard to the subjective response, ankle systolic indices, maximum limb blood flow or whole blood viscosity. It is concluded that oxpentifylline , when taken in oral form at the dose used in this study, increased erythrocyte deformability without conferring any clinical or haemorrheological benefit to patients with intermittent claudication.

A comparison of teicoplanin versus cephradine plus metronidazole in the prophylaxis of post-operative infection in vascular surgery.

A total of 272 patients were enrolled into this prospective, unblinded, randomized comparison of single-dose teicoplanin vs three doses of cephradine plus metronidazole as prophylaxis for vascular surgery at St James's and Seacroft Hospitals, Leeds, UK. In all, 71.3% of patients (194/272) were enrolled at St James's University Hospital. Patients received either a single dose of teicoplanin, 6 mg/kg i.v., or cephradine, 1 g i.v. with metronidazole, 1 g rectally, at induction of anaesthesia followed by two further 1 g doses of cephradine and metronidazole 8 and 16 hours later. There were 136 patients in each treatment group. The most common operations were femoropopliteal grafts (96) and aortic aneurysm repairs (47). In the 'intention-to-treat' analysis, primary wound infections were seen in 4.4% of patients (6/136) receiving teicoplanin and 5.9% of patients (8/136) receiving cephradine plus metronidazole (95% CI -6.7%, +3.8%). Other disturbances to wound healing occurred in 23 patients (11 in the teicoplanin and 12 in the cephradine plus metronidazole group). Secondary respiratory tract infections occurred in 17 patients (8 receiving teicoplanin and 9 receiving cephradine plus metronidazole). In the evaluable patients analysis, primary wound infections occurred in 3.5% of patients (4/114) receiving teicoplanin and 5.1% of patients (6/117) receiving cephradine plus metronidazole. Staphylococcus aureus and Proteus sp. were the most common pathogens in primary wound infections. Despite the absence of Gram-negative cover in the teicoplanin group, Gram-negative infections occurred more often in the cephradine plus metronidazole group. Surgery of the lower extremities carried the highest risk of post-operative infection. Rates of infection were significantly higher at Seacroft Hospital (P = 0.001), and significantly higher for cephradine plus metronidazole between the two hospitals (P = 0.0008). Adverse events occurred in 40 patients receiving teicoplanin (29.4%) and 39 patients receiving cephradine plus metronidazole (28.7%). In 19 patients receiving teicoplanin (14%) and 15 receiving cephradine plus metronidazole (11%) these events were considered to be related to the study drugs. The most often reported events were infections, cardiac events and vascular phenomena (haematoma or emboli). Marked changes in haematological parameters and liver function tests were noted seven days after operation in patients in each treatment group, but these resolved quickly as the effects of the operation subsided. ESR remained elevated in both groups at the six-month follow-up assessment. It is concluded from this two-centre study that a single dose of teicoplanin shows similar efficacy to a three-dose regimen of cephradine plus metronidazole as prophylaxis for wound infection in vascular surgery. Both regimens were well tolerated, and there was an equal incidence of adverse events in the two regimens, which reflected the poor general health status of this elderly study population.

Radionuclide limb blood flow measurements to resolve diagnostic problems in vascular surgery.

This paper describes the application of radionuclide limb blood flow measurements in 60 patients presenting to the vascular surgeons with exercise-induced leg pain. All patients were considered to be diagnostic problems since either their symptoms were atypical for peripheral vascular disease, or they had normal peripheral pulses and/or a normal ankle/brachial pressure index. Thirty-one patients were ultimately shown to have peripheral vascular disease and underwent treatment. In all these cases the limb blood flow to one or both legs was below the normal range. Twenty-three patients were shown, by myelography, computed tomography or plain radiography, to have orthopaedic disease and in all cases their limb blood flow to both legs was within the normal range. In five patients, the limb blood flow was normal and the symptoms spontaneously resolved, no cause for the leg pain having been found (one patient refused angiography). Radionuclide limb blood flow is a simple and reliable diagnostic test which is superior to the assessment of peripheral pulses or their ankle to brachial pressure index in resolving diagnostic problems in vascular surgery.

Dual tracer technique to measure salvaged red cell survival following autotransfusion in aortic surgery.

The survival of autotransfused red cells was measured for two salvage devices used in 12 elective aortic reconstructions. Six patients underwent cell salvage with the Solco-trans device and six with the Haemonetics cell saver. A double tracer technique was used to take account of post-operative blood loss and fluid replacement. Comparison was made with the results of a group of normal volunteers. A comparison was made of the labelling efficiency of damaged and undamaged red cells using chromium to check that red cells damaged during autotransfusion can be labelled. No significant difference was seen. There was no significant difference in red cell survival between the volunteer group and either of the two salvage device groups. These results suggest that red cell survival is not compromised by the autotransfusion process using these two devices.

Radionuclide limb blood flow in peripheral vascular disease: a review of 1100 measurements.

Radionuclide limb blood flow measurements using 99Tcm-labelled human serum albumin and a gamma camera have been performed on normal volunteers and on patients with suspected or confirmed peripheral arterial disease. The normal range of flow was found to be 10.0-22.3 ml per 100 ml tissue per min. Flow in the symptomatic legs of patients with arterial disease varied from 9.0 ml per 100 ml tissue per min in mild claudication to less than 1.0 ml per 100 ml tissue per min in rest pain. The technique has been used as an initial screening procedure, to resolve diagnostic problems, to measure objectively the treatment response and to assess patients with critical ischaemia. The results of 1100 measurements are reported and the clinical utility in routine vascular surgical practice is discussed.