A scoring system to predict the outcome of long femorodistal arterial bypass grafts to single calf or pedal vessels.

OBJECTIVES: The aim of this study was to develop a scoring system to predict the outcome of long femorocrural and femoropedal bypass grafts performed for critical limb ischaemia. SETTING: Teaching hospital. METHODS: An analysis of 109 consecutive femorodistal bypass grafts performed for critical lower limb ischaemia between June 1991 to December 1994. Factors shown to affect the outcome were: inflow, number of patent calf vessels, graft material, straight flow to the foot and patent pedal vessels. These variables were weighted according to their relative significance (multivariate Cox regression) and a scoring system (ranging from 0 to 10) was developed. RESULTS: Patients with a preoperative score of 0-4 (n = 35) showed a secondary patency of 36% at 1 month, 12% at 3 months and 0% at 10 months (Cum SE = 6.90/0.0). Secondary patency rates for the 46 patients with score 5-7 were 88.7% at 3 months, 56.3% at 12, and 45.1% at 2 and 3 years (Cum SE = 9.82), while the respective values for the 28 patients with score 8-10 were 92.7%, 88.5% and 81.7% (Cum SE = 8.08). The difference was highly significant (p = 0.000) in all tests of equality. In addition, the median total hospital cost was 12,600 Pounds for the group 0-4 compared with 8100 Pounds (group 5-7) and 4400 Pounds (group 8-10) (p = 0.0085). CONCLUSIONS: This preoperative scoring system appears to correlate well with the outcome of distal revascularisation to single calf or pedal vessels. If applied to patient selection, it could significantly reduce the total hospital cost per leg saved. A prospective testing of its predictive ability is needed and is in progress.

Successful intraarterial thrombolysis of an ischemic limb four days after laparoscopic cholecystectomy.

Intraarterial thrombolysis is usually contraindicated after abdominal surgery because of the risk of bleeding. However, it is a highly effective treatment for embolic acute limb ischemia, particularly for clearing the distal vessels. We report a case in which intraarterial thrombolysis was safely used 4 days after laparoscopic cholecystectomy in a patient with an acutely ischemic leg due to embolus.

Low-molecular-weight heparin versus warfarin for prevention of recurrent venous thromboembolism: a randomized trial.

A group of 105 consecutive patients with venographically proved major acute deep vein thrombosis (DVT) were randomized in an open prospective study to evaluate the comparative efficacy and safety of a fixed dose of subcutaneous low-molecular-weight heparin (LMWH) and warfarin for the prevention of recurrent venous thromboembolism. Four patients developed venographically proved recurrent DVT during the 3 months of treatment: three in the LMWH group and one in the warfarin group. Nonfatal pulmonary embolism occurred in two patients in the LMWH group and in one in the warfarin group. Five of the 55 patients (10%) in the warfarin group and none of the 50 patients in the LMWH developed bleeding complications (two-tailed Fisher exact test, p = 0.06). A preliminary assessment of the costs indicated that treatment with LMWH was less expensive by Pounds 900 per patient than warfarin. In conclusion, the fixed daily dose of LMWH and the adjusted dose of warfarin therapy were of similar efficacy in preventing recurrence of DVT. However, warfarin therapy, despite strict laboratory control, is associated with more frequent side effects and is expensive. Another study with a higher dose of LMWH is recommended.

The changing pattern of venous thromboembolic disease.

A review of 14,667 necropsy reports for every year from 1965 to 1990 and 6,436 diagnostic venograms performed from 1976 to 1990 was undertaken at a single teaching hospital. A progressive reduction in the percentage of necropsies reporting fatal pulmonary embolism from 6.1 to 2.1%, occurred over the 25-year period (chi(2) tests for linear trend with time p < 0.00001). Over the last decade, there has been a significant reduction in the rate of venographically diagnosed postoperative deep vein thrombosis (DVT) from 49.9 to 24.7 per 100,000 population (p < 0.0001) which was in marked contrast to the constant rate of non-postoperative DVT. Our findings suggest that the introduction of thromboprophylactic measures, in addition to changes in hospital practice, may have had a highly significant effect on the pattern of this serious, but potentially avoidable disease.

A dose ranging study to evaluate dermatan sulphate in preventing deep vein thrombosis following total hip arthroplasty.

Dermatan sulphate catalyses thrombin inhibition by heparin cofactor II; it has a lower haemorrhagic to antithrombotic ratio than that of heparin in animal models. Consecutive patients aged forty years or more, electively undergoing total hip replacement under general anaesthesia, were randomly allocated to one of three dosage regimens of dermatan sulphate (MF701, Mediolanum Farmaceutici) given intramuscularly. These were 200 mg once daily (n = 50), 200 mg twice daily (n = 52) and 300 mg twice daily (n = 51), administered from twenty-four hours pre-operatively until the tenth postoperative day. The overall incidence of DVT assessed by bilateral venography was 53%, 51% and 34% respectively (Chi-square test for trend p = 0.06). The incidence of major proximal DVT was 10.6%, 8.5% and 2.1% respectively. Pulmonary embolism (PE) and bleeding were assessed in all 153 patients. There was one case of PE in each dose group. The incidence of bleeding episodes, volume of blood lost and blood transfusion requirements were low and showed no increase with increasing dose. The patients were followed up 4-8 weeks after discharge. We conclude that the two lower doses were subtherapeutic in this population, however dermatan sulphate given 300 mg twice daily, proved to be efficacious with an incidence of proximal major DVT of 2.1% and a low incidence of bleeding complications. A trial of dermatan sulphate 300 mg twice daily compared to standard prophylactic agents is needed.

Low-molecular weight heparin versus aspirin and dipyridamole after femoropopliteal bypass grafting.

Low-molecular weight heparin has theoretical advantages over aspirin and dipyridamole in maintaining vascular-graft patency by virtue of its better antithrombotic effect and antiproliferative activity on vascular, smooth-muscle cells. We tested the hypothesis that low-molecular weight heparin would be more effective than aspirin and dipyridamole in maintaining graft patency in patients undergoing femoropopliteal bypass grafting. Patients were randomised to receive either a daily injection of 2500 IU low-molecular weight heparin, or 300 mg aspirin with 100 mg dipyridamole 8 hourly for 3 months. 94 patients were randomised to low-molecular weight heparin and 106 to aspirin and dipyridamole. Patients were stratified according to indication for surgery and were followed up for 1 year. Kaplan-Meier estimate of graft patency showed 87% graft survival on low-molecular-weight heparin and 72% on aspirin and dipyridamole at 6 months. At 12 months, the respective figures were 78% and 64%. Stratified survival analysis showed that this benefit was confined to those having salvage surgery (log rank test p = 0.0006); for those having surgery for claudication there was no significant benefit. No major bleeding events occurred in either group. We conclude that low-molecular weight heparin is better than aspirin and dipyridamole in maintaining femoropopliteal-graft patency in patients with critical limb ischaemia undergoing salvage surgery. This treatment should have considerable cost benefits.

Endoscopic transthoracic sympathectomy in the treatment of hyperhidrosis.

A 5-year experience of 50 endoscopic transaxillary dorsal sympathectomies is presented. The procedure was successful in either curing or improving the symptoms of hyperhidrosis in the great majority of patients. The commonest side effects were compensatory sweating (75%) and gustatory sweating (48%); despite this, there was an extremely high level of patient satisfaction. Permanent Horner's syndrome did not occur. The procedure is effective, simple, cheap, and requires only an overnight stay; and is recommended as the method of choice for the surgical treatment of upper limb hyperhidrosis.

Uptake of a catecholic cephalosporin by the iron transport system of Escherichia coli.

beta-Lactam antibiotics containing a catechol moiety show potent activity against Gram-negative bacteria, particularly organisms grown under iron-limited conditions, suggesting that the iron-regulated outer membrane proteins (IROMPs) play a role in antibiotic uptake. A catecholic C(7) alpha-formamido-substituted cephalosporin showed increased penetration into Escherichia coli cells grown in an iron-deficient medium compared with cells grown in a medium supplemented with iron. In contrast, penetration of the corresponding monohydroxyphenyl analogue was not influenced by iron concentration. Susceptibility studies with mutants of E. coli lacking one or more IROMPs suggested that the catecholic analogue was able to utilize the Fiu (83 kDa) and Cir (74 kDa) proteins, but not the enterobactin receptor FepA (81 kDa). Mutants lacking both Fiu and Cir showed a specific decreased susceptibility for catechol-containing cephalosporins. Radio-ligand binding studies with a Fe-catecholic cephalosporin confirmed an association with these proteins.

Beta-lactamase stability of temocillin.

The stability of temocillin to 12 different beta-lactamase preparations was studied using high pressure liquid chromatography and was compared with that of aztreonam, cefotetan and cefotaxime. Temocillin was the most stable beta-lactam examined, being as stable as cefotetan to most of the beta-lactamases tested. However, cefotetan was hydrolysed at measurable rates by the beta-lactamase of Enterobacter cloacae P99, in contrast to temocillin which was completely stable to this enzyme. Aztreonam was hydrolysed at a slow rate by many of the preparations, being especially labile to the enzyme from Klebsiella oxytoca K1. Cefotaxime was hydrolysed at varying rates by all the preparations.

In vitro antibacterial properties of BRL 36650, a novel 6 alpha-substituted penicillin.

BRL 36650 is a new type of penicillin in which a formamido group has been introduced into the 6 alpha-position of the nucleus. The compound is highly active against aerobic gram-negative bacteria and is stable to a wide range of beta-lactamases produced by these organisms. Against members of the family Enterobacteriaceae, BRL 36650 was considerably more active than piperacillin, particularly against beta-lactamase-producing strains, and showed a similar level of activity to moxalactam, aztreonam, and the third-generation cephalosporins cefotaxime and ceftazidime. Against Pseudomonas aeruginosa and other Pseudomonas species, BRL 36650 was more active than piperacillin, cefoperazone, and aztreonam and compared favorably with ceftazidime. BRL 36650 was highly active against Haemophilus influenzae and Neisseria gonorrhoeae, including beta-lactamase-producing strains, and against Acinetobacter calcoaceticus. Clinical isolates of Enterobacter species and P. aeruginosa which showed markedly reduced susceptibility to cefotaxime, ceftazidime, and aztreonam were only slightly less susceptible to BRL 36650. Against Bacteroides fragilis and most gram-positive bacteria, BRL 36650 showed only a low level of activity. BRL 36650 was found to be only 35% bound to human serum protein, and the antibacterial activity was little affected by the presence of serum. In contrast, the composition of the test medium influenced the activity of BRL 36650 slightly, and an antagonistic effect could be demonstrated between the compound and a component of certain Mueller-Hinton media.

BRL 17421, a novel beta-lactam antibiotic, highly resistant to beta-lactamases, giving high and prolonged serum levels in humans.

BRL 17421 is a new semisynthetic beta-lactam antibiotic with an unusual spectrum of antibacterial activity. The compound exhibits exceptional stability to a wide range of bacterial beta-lactamases and is active against the majority of Enterobacteriaceae, including strains highly resistant to many of the penicillins and cephalosporins currently available. Among the clinical isolates of Enterobacteriaceae tested, the frequency of strains resistant to BRL 17421 was found to be low, and there was a slow rate of emergence of resistance during in vitro studies. BRL 17421 was highly active against Haemophilus influenzae and Neisseria gonorrhoeae, including beta-lactamase-producing strains. The compound was markedly less active against Pseudomonas aeruginosa and Bacteroides fragilis than against the Enterobacteriaceae. Against the gram-positive bacteria, BRL 17421 showed a very low level of activity. BRL 17421 was found to be 85% bound to human serum, and the antibacterial activity was diminished two- to fourfold in the presence of human serum. Against experimental infections in mice, the activity of BRL 17421 reflected the properties observed in vitro. Studies in human volunteers showed unusually high and prolonged serum concentrations of the compound after parenteral dosage, with a serum half-life of about 5 h, and approximately 85% of the dose was recovered unchanged in the urine. BRL 17421 was poorly absorbed after oral administration. The compound was well tolerated after intramuscular and intravenous administration in volunteers, with no adverse side effects.