Multidisciplinary approach to carotid stenting.

BACKGROUND: Stroke neurologists, vascular surgeons, interventional neuroradiologists and interventional cardiologists have embraced carotid angioplasty and stenting (CAS) because of potential advantages over carotid endarterectomy (CEA). At Austin Health, a multidisciplinary neuro-interventional group was formed to standardise indications and facilitate training. The aims of this study were to describe our organisational model and to determine whether 30-day complications and early outcomes were similar to those of major trials. METHODS: A clinical protocol was developed to ensure optimal management. CAS was performed on patients with high medical risk for CEA, with technically difficult anatomy for CEA, or who were randomised to CAS in a trial. RESULTS: From October 2003 to May 2008, 47 patients (34 male, mean age 71.5) underwent CAS of 50 carotid arteries. Forty-three cases had ipsilateral carotid territory symptoms within the previous 12 months. The main indications for CAS were high risk for CEA (n= 17) and randomised to CAS (n= 21). Interventionists were proctored in 27 cases. The procedural success rate was 94% with two cases abandoned because of anatomical problems and one because of on-table angina. Hypotension requiring vasopressor therapy occurred in 12 cases (24%). The duration of follow up was one to 44 months (mean 6.8 months). The 30-day rate of peri-procedural stroke or death was 6% and the one-year rate of peri-procedural stroke or death or subsequent ipsilateral stroke was 10.6%. Restenosis occurred in 13% (all asymptomatic). CONCLUSION: A multidisciplinary approach is a useful strategy for initiating and sustaining a CAS programme.

A systematic review of stapled hemorrhoidectomy.

HYPOTHESIS: Use of circular stapled hemorrhoidectomy will result in the same or improved safety and efficacy outcomes as those of the conventional methods for hemorrhoidectomy in patients with hemorrhoids. DATA SOURCES: Studies on stapled hemorrhoidectomy were identified using PREMEDLINE and MEDLINE (June 1966-June 2001), EMBASE (January 1980-June 2001), Current Contents (June 1993-June 2001), Ovid HEALTHSTAR (January 1975-June 2001), the National Institutes of Health Clinical Trials database (searched June 13, 2001), and The National Coordinating Centre for Health Technology Assessment database (searched June 14, 2001). The search terms were as follows: haemorrhoid* and (stapl* or convent*) or hemorrhoid* and (stapl* or convent*). The Cochrane Library (2001, issue 2) was searched using the search terms haemorrhoid* or hemorrhoid*. STUDY SELECTION: Articles detailing randomized controlled trials were included if they compared circular stapled with conventional hemorrhoidectomy and provided relevant safety and efficacy outcome information. DATA EXTRACTION: Data from all included studies were extracted using standardized data extraction tables that were developed a priori. In addition, the randomized controlled trials were examined with respect to the adequacy of allocation concealment, handling of those unavailable for follow-up, and any other aspect of the study design or execution that may have introduced bias. DATA SYNTHESIS: Seven randomized controlled trials met the inclusion criteria. A meta-analysis was conducted when the studies had comparable outcomes, inclusion criteria, and follow-up. There was reasonably clear evidence in favor of the stapled procedure for bleeding at 2 weeks (relative risk, 0.55; 95% confidence interval, 0.37-0.82) and length of hospital stay (weighted mean difference, -0.89 days; 95% confidence interval, -1.42 to -0.36). Other less robust results in favor of the stapled hemorrhoidectomy related to pain, bleeding, anal discharge, wound healing, tenderness to per rectal examination, incontinence scores, earlier return of bowel function, analgesic requirement, and resumption of normal activities. One trial showed that prolapse occurred at significantly higher rates in the stapled hemorrhoidectomy group. However, the outcomes were poorly reported and generally showed statistically significant heterogeneity. CONCLUSIONS: Stapled hemorrhoidectomy may be at least as safe as conventional hemorrhoidal surgical techniques. However, the efficacy of the stapled procedure compared with the conventional techniques could not be determined. More rigorous studies with longer follow-up periods and larger sample sizes need to be conducted.

Dextran reduces embolic signals after carotid endarterectomy.

One hundred fifty patients undergoing carotid endarterectomy were randomly assigned to receive intravenous 10% dextran 40 or placebo. Transcranial Doppler monitoring of the ipsilateral middle cerebral artery 0 to 1 hour postoperatively detected embolic signals in 57% of placebo and 42% of dextran patients, with overall embolic signal counts 46% less for dextran (p = 0.052). Two to 3 hours postoperatively, embolic signals were present in 45% of placebo and 27% of dextran patients, with embolic signal counts 64% less for dextran (p = 0.040). We conclude that dextran reduces embolic signals within 3 hours of CEA.

Modification of surface histidine residues abolishes the cytotoxic activity of Clostridium difficile toxin A.

Clostridium difficile toxin A displays both cytotoxic and enterotoxic activities. It has recently been demonstrated that toxin A exerts its cytotoxic effect by the glucosylation of the small GTP-binding proteins of the Rho family. Diethyl pyrocarbonate, at pH 7.0, was used to chemically modify exposed histidine residues on toxin A. Modification of toxin A with diethyl pyrocarbonate abolished both its cytotoxic activity and the ability of the toxin to bind Zn-Sepharose gel. Treatment of toxin A with [(14)C]-diethyl pyrocarbonate revealed concentration dependent labelling of histidine residues on the toxin molecules. The effects of diethyl pyrocarbonate could be reversed by hydroxylamine treatment. These data suggest the modified histidine residues on toxin A are critical to its cytotoxic activity. Histidine modification had no effect on the glucosyl transferase enzyme activity of toxin A. However, modification abolished the 'cold' binding of toxin to bovine thyroglobulin in an ELISA and reduced ligand binding activity in a rabbit erythrocyte haemagglutination assay. The data suggest that the histidine residues may be crucial to the receptor-binding activity of toxin A. Exposed histidines on toxin A are available for zinc chelation, and these have been exploited in the development of a novel purification protocol for toxin A using zinc-chelating chromatography.

Biomechanics of ankle and hindfoot injuries in dynamic axial loading.

Twenty-three Post Mortem Human Surrogate (PMHS) limbs were impacted using a test set up that was developed to simulate the loading conditions seen in a frontal collision. Articulation studies were performed on each limb prior to impact. Failure occurred at impact loads of 5.7+/-1.9 kN (resultant tibial failure load 6.4+/-1.9 kN) and the following injuries were generated: 9 intra-articular calcaneal fractures; 1 talar neck and 2 talar body fracture; 3 intra-articular distal tibial (pilon) fractures; 2 malleolar fractures; 3 soft tissue injuries and 3 had no detectable injury. The impact test conditions were replicated with a Hybrid III leg in a first attempt at developing injury risk functions for the dummy. This study has demonstrated the significance of preload through muscle tension and the intrinsic properties of PMHS specimens in the generation of severe ankle and hindfoot injury.

Association of polymorphism within the promoter of the tumor necrosis factor alpha gene with increased risk of preterm premature rupture of the fetal membranes.

OBJECTIVE: The rarer allele of a polymorphism within the promoter region at position -308 of the gene for tumor necrosis factor alpha is associated with increased gene transcription. In this study we tested the hypothesis that this rarer allele is associated with spontaneous preterm birth. STUDY DESIGN: We conducted a case-control study of women admitted to our labor and delivery unit. To assess data from a single racial group with a high incidence of preterm birth we restricted our analysis to African American women, who contributed 73.6% of the samples collected during the study period. Case patients (n = 55) were defined as women who were delivered before 37 weeks' gestation after idiopathic preterm labor or preterm premature rupture of membranes. Control subjects (n = 110) included women who were delivered after 37 weeks' gestation and had no history of preterm delivery. We also performed subgroup analyses of women with idiopathic preterm labor and delivery (n = 29) and women who were delivered preterm after preterm premature rupture of the fetal membranes (n = 26). RESULTS: Although carriers (homozygotes plus heterozygotes) of the rarer allele of the polymorphism at position -308 in the gene for tumor necrosis factor alpha were not significantly more common among women who were delivered preterm (n = 24/55, 44%) than among control subjects (n = 33/110, 30%, P =.08, odds ratio 1.81, 95% confidence interval 0.92-3.54), carriers of the rarer allele were more common among women who were delivered preterm after preterm premature rupture of membranes (n = 15/26, 58%) than among control subjects (P =.008, odds ratio 3.18, 95% confidence interval 1.33-7.83). CONCLUSIONS: Our results demonstrate an association between allelic variants of the polymorphism at position -308 in the gene for tumor necrosis factor alpha and preterm birth after preterm premature rupture of the fetal membranes. We hypothesize that host susceptibility to environmental factors, such as hyperresponsiveness of the gene for tumor necrosis factor alpha to genital tract infection, may promote preterm premature rupture of the fetal membranes and subsequent preterm delivery.

Transcranial Doppler microembolus detection in the identification of patients at high risk of perioperative stroke.

OBJECTIVES: Perioperative ischaemic stroke is the leading cause of morbidity and mortality associated with carotid endarterectomy (CEA). The aim was to test the hypotheses that the detection of microembolic ultrasonic signals (MES) with transcranial Doppler ultrasound (TCD) during and after the operation may be of value in identifying patients at increased perioperative stroke risk. DESIGN: Open prospective case series. PATIENTS AND METHODS: Eighty-one consecutive patients undergoing CEA with TCD monitoring. Preoperative, intraoperative and interval postoperative TCD monitoring of the middle cerebral artery (MCA) ipsilateral to the operated carotid artery. On-line pre- and intraoperative MES counting and blinded off-line analysis of postoperative MES counts. End-points were any focal neurological deficit and death at 30 days postoperatively. RESULTS: MES were detected in 94% of patients intraoperatively and 71% of cases during the first postoperative hour. MES counts ranged from 0 to 25 per operative phase (range of median counts 0-8) and from 0 to 212 per hour postoperatively (range of median counts 0-4). Eight cases (10%) developed postoperative MES counts greater than 50/h. Five of these eight cases evolved ischaemic neurological deficits in the territory of the insonated MCA, indicating a strong association between frequent postoperative microembolism and the development of early cerebral ischaemia (chi 2 = 34.2, p < 0.0001). Intraoperative MES were not associated with clinical outcome measures. CONCLUSIONS: MES counts of greater than 50/h in the early postoperative phase of carotid endarterectomy are predictive of the development of ipsilateral focal cerebral ischaemia.

Transcranial Doppler detected cerebral microembolism following carotid endarterectomy. High microembolic signal loads predict postoperative cerebral ischaemia.

Cerebral ischaemia, the most frequent serious complication of carotid endarterectomy (CEA), usually occurs in the early postoperative period and is often the result of thromboembolism. We hypothesized that the early postoperative detection of microembolic ultrasonic signals (MES) with transcranial Doppler ultrasound (TCD) may be of value in identifying patients at risk of postoperative cerebral ischaemia and that the MES rate may be an important determinant in risk prediction. Sixty-five patients undergoing CEA were studied at intervals up to 24 h postoperatively with TCD insonation of the middle cerebral artery ipsilateral to the operation side. Study design was open and prospective with blinded off-line analysis of MES counts. End-points were any focal ischaemic neurological deficit and/or death up to 30 days postoperatively. MES were detected in 69% of cases during the first hour postoperatively with counts ranging from 0 to 212 MES/h (means 19 MES/h; SEM +2- 4.5; median 4 MES/h). In seven cases (10.8%) counts were > 50 MES/h. Five of these seven cases developed ischaemic neurological deficits in the territory of the insonated middle cerebral artery during the monitoring period. The positive predictive value of counts > 50 MES/h for cerebral ischaemia was 0.71. Frequent signals (> 50 MES/h) occur in approximately 10% of cases in the early postoperative phase of CEA and are predictive for the development of ipsilateral focal cerebral ischaemia.

Peptide substrate specificity and properties of the zinc-endopeptidase activity of botulinum type B neurotoxin.

Clostridium botulinum type B neurotoxin has been shown to be a zinc endopeptidase specific for vesicle-associated membrane protein (VAMP). A synthetic peptide of human/rat VAMP-2 [VAMP-2-(60-94)] is cleaved by the neurotoxin with the same specificity as that demonstrated for the membrane-associated protein (at the Gln76-Phe77 bond) and has been used to study the properties of the endopeptidase activity of the neurotoxin. Cleavage of the VAMP-2 peptide was demonstrated by both botulinum type B neurotoxin (Km = 3.3 x 10(-4) M) and by its purified light subunit (Km = 3.5 x 10(-4) M). The endopeptidase displayed a pH optimum of 7.0-7.5 and was inhibited by greater than 0.2 M NaCl and greater than 0.05 M sodium phosphate. Neurotoxin which had been inactivated by dialysis against EDTA could be re-activated by incubation with various divalent cations, notably Zn2+ and Cu2+. The substrate specificity of botulinum type B neurotoxin was studied using various analogues of VAMP-2 (60-94). The neurotoxin cleaved selectively to the N-terminal side of phenylalanine and tyrosine; no activity was observed with either leucine, valine or alanine in the P'1 position. The properties of the P1 amino acid were less critical; the neurotoxin cleaving the C-terminus of glutamine, asparagine and alanine. A substrate analogue with valine in the P1 position corresponding to the sequence of rat VAMP-1 was not cleaved. The rate of cleavage of a substrate analogue representing the sequence of human VAMP-1, however, was more than twofold that of the VAMP-2 peptide. The properties and substrate specificity of botulinum type B neurotoxin suggest that the toxin represents a novel class of endopeptidase which requires a specific peptide substrate conformation for the expression of proteolytic activity.

Supplementation of an adapted formula with bovine lactoferrin: 1. Effect on the infant faecal flora.

The development of the infant faecal flora was studied over the first three months of life in infants receiving breast milk, a modern adapted formula and adaptations of this formula. Breast-fed infants developed a flora rich in Bifidobacterium sp. Facultative anaerobes were ubiquitous, but in relatively small numbers within the diet group. Other obligate anaerobes, such as Clostridium sp. and Bacteriodes sp. were rarely isolated. Standard formula produced a flora rich in bifidobacteria, but the growth of facultative organisms was not suppressed by this diet. Clostridium sp. and Bacteroides sp. were more common in this feeding group. After the addition of lactoferrin at 10 mg/100 ml to the formula diet, a flora similar to that of the standard formula-fed babies was achieved. Lactoferrin at 100 mg/100 ml was able to establish a "bifidus flora" in half of the babies given this formula, but only at age three months. Clostridium sp. and Bacteroides sp. were common faecal isolates from babies receiving both the lactoferrin diets.

Venous reflux patterns in the popliteal fossa.

Incompetent veins in the popliteal fossa were assessed with duplex ultrasound in 123 legs of 104 patients. In 91 cases the venous reflux was the result of a single incompetent vein draining into the deep system. In 32 cases duplex ultrasound demonstrated a combination of incompetent veins. With the exception of 3 patients duplex scanning accurately localised the incompetent veins and their "junctions" with the deep system. In 48 legs the reflux signal, detected in the surface vein, extended back beyond the "junction" into a proximal segment of the popliteal vein or superficial femoral vein; in most cases the distal popliteal vein remained competent. Six distinct venous reflux patterns were identified in the popliteal fossa, which seemed to correlate with the severity of related clinical symptoms.

The detection of early femoro-distal vein graft stenosis by treadmill exercise testing.

A prospective study of 125 femoro-distal vein bypass grafts (103 patients) was undertaken to assess the role of treadmill exercise testing in the detection and correction of early vein graft stenosis. Patients were followed at 1,3,6,12 months and then annually with routine clinical assessment, palpation of pulses and resting Doppler ankle/brachial index. In addition, the Doppler index was repeated after 5 minutes exercise on a treadmill set at 5 degrees and 3 km/hr. Follow-up has been carried out for a mean of 24 months (range 3-48 months) and during that time 30 vein grafts (28 patients) were submitted to angiography. This revealed vein graft stenosis in 15, native vessel disease in 11 and no morphologic abnormality in 4. One additional graft was suspected to have a stenosis but occluded before angiography could be carried out. At the time of detection by the treadmill test, 8 of the 15 (53%) confirmed vein graft stenoses, and 4 of 11 (36%) native vessel stenoses would not have been detected by clinical assessment or resting Doppler pressure measurements. The 15 vein graft stenoses which were corrected all remain patent, suggesting that treadmill testing is of value in the detection and prevention of early femoro-distal vein graft occlusion.

Prospects for further approximation of infant formulas to human milk.

In this study: breast-fed babies developed a flora rich in bifidobacteria with lower counts of enterobacteria; bacteroides and clostridia, if detected were usually present in low numbers; formula-fed babies usually had high counts of bifidobacteria and enterobacteria; bacteroides plus clostridia were isolated with higher counts and from a larger percentage of babies than in the breast-fed group; and conalbumin did not appear to bring the gut flora of formula-fed babies nearer to that observed in breast-fed infants.

Acute aorto-caval fistula: a complication of abdominal aortic aneurysm.

Three patients, with acute spontaneous aorto-caval fistulae, are described. The important aspects of the diagnosis and treatment of these fistulae are discussed and the recommended anaesthetic and surgical management presented.

Distal profunda femoris to popliteal artery bypass for patients with a short length of long saphenous vein.

A technique of distal profunda femoris to popliteal artery bypass is described in two patients in whom the length of long saphenous vein available for grafting was too short for a conventional femoropopliteal bypass. Because each patient has a large profunda system which was free from proximal disease, a bypass was constructed betweeen the distal profunda femoris and the upper popliteal arteries, utilizing the short length of long saphenous vein available. Both patients had complete relief of their symptoms and objective evidence of improvement.

Aneurysm formation in an expanded microporous polytetrafluorethylene graft.

Microporous expanded polytetrafluoroethylene (PTFE) has recently been proposed as an arterial graft. Although excellent graft patency rates have been achieved both experimentally and clinically, aneurysm formation of the graft has occurred in a small number of cases. This report describes a further case of aneurysm formation in a PTFE graft five months after insertion. We discuss the possible causes of graft aneurysm formation and a newly developed reinforced form of PTFE graft.

Definitive emergency treatment of perforated duodenal ulcer.

A retrospective survey was made of all patients with a proved diagnosis of perforated duodenal ulcer admitted to a regional hospital during a recent six year period. The over-all mortality from this condition in the 192 patients was 11.4 per cent and mortality after operation, 6.3 per cent. One hundred and seventy-six patients were treated surgically. Seventy-seven patients underwent simple suture only with a mortality of 13 per cent and are compared with 99 patients treated by emergency vagotomy and pyloroplasty procedures with a 1 per cent mortality. Emergency definitive operations were performed without increased morbidity, mortality or hospital stay by junior surgeons with greatly improved long term results compared with simple suture. At the present time, emergency vagotomy and pyloroplasty procedures are the treatment of choice for a perforated duodenal ulcer.