bluuebunny/crossref_metadata_2025 huggingface dataset:
Archaeology of landscape change in south-west Scotland, 6000 BC–AD 1400
Authors: Banks Iain , Duffy Paul R J , MacGregor Gavin , Campbell Ewan , Duncan John S , Miller Jennifer , Ramsay Susan , Smith Catherine , Stuart Eland , Speller Keith , Halliday Stuart , Will Bob , Arthur John , Evans Caitlin , Francoz Charlotte
Published: March 2022

Between 1996 and 1998, Glasgow University Archaeological Research Division (GUARD) undertook a programme of archaeological investigation at the headquarters of William Grant and Sons Distillers Ltd, Girvan (NGR: NS 200 006). The work revealed evidence of occupation and use from prehistoric times, including palaeobotanical and pedological evidence of deliberate prehistoric tree clearance, and the presence of six discrete deposits of burnt mound material. The project also confirmed the survival of archaeological deposits relating to the occupation of the medieval moated enclosure of Ladywell. A number of worked lithics, indicative of prehistoric tool making or maintenance, were also recovered. The excavation and post-excavation work allowed an opportunity to explore the occupational, ecological and geomorphological history of the entire length of the valley, from the immediate post-glacial period to the present day. The results contribute significantly to our understanding of the changing patterns of human interaction with environment and landscape over a period of some 10,000 years, both in the immediate area and beyond.
Calcium‐dependent translocation of sorcin to membranes: functional relevance in contractile tissue
Authors: Meyers Marian B. , Zamparelli Carlotta , Verzili Daniela , Dicker Adam P. , Blanck Thomas J.J. , Chiancone Emilia
Published: July 2002

Sorcin, a 22 kDa calcium binding protein present in abundance in cardiac tissue and in multi‐drug resistant cells and previously described as a soluble protein, is now shown to undergo a calcium‐dependent translocation process from the cytosol to cellular membranes in both systems. The translocation process takes place also in E. coli BL21 cells that express recombinant sorcin, r‐sorcin, and can be exploited in the purification of the protein. Calcium binding to purified r‐sorcin occurs at micromolar concentrations of the metal and is accompanied by a conformational change that renders the protein soluble in the non‐ionic detergent Triton X‐114. This finding suggests that lipids are the target of sorcin on cellular membranes. The possible significance of the calcium‐dependent translocation of sorcin in the specialized functions of sorcin‐expressing cells is discussed.
Bifunctional phosphomannose isomerase/GDP‐D‐mannose pyrophosphorylase is the point of control for GDP‐D‐mannose biosynthesis in Helicobacter pylori
Authors: Wu Bingyuan , Zhang Yingxin , Zheng Rong , Guo Cuiwen , Wang Peng George
Published: July 2002

In this report a recombinant bifunctional phosphomannose isomerase/GDP‐D‐mannose pyrophosphorylase from Helicobacter pylori has been studied. The enzyme catalyzes the first and third steps of GDP‐D‐mannose biosynthesis from D‐fructose‐6‐phosphate. The first step, isomerization from D‐fructose‐6‐phosphate to D‐mannose‐6‐phosphate, is found to be rate‐limiting in GDP‐D‐mannose biosynthesis due to feedback inhibition. The inhibition is of non‐competitive (mixed) type. As the enzyme is found only in bacteria probably participating in capsular polysaccharide biosynthesis, it could be a specific therapeutic target against bacterial infection.
Identification of a novel prokaryotic HEAT‐repeats‐containing protein which interacts with a cyanobacterial IscA homolog
Authors: Morimoto Kozo , Nishio Kazuaki , Nakai Masato
Published: July 2002

IscA homologs are known to be involved in iron–sulfur cluster formation in various organisms. Recombinant proteins of two IscA homologs from the cyanobacterium Synechocystis PCC 6803, designated SLR1417 and SLR1565, were purified. The absorption spectrum of purified SLR1565 was typical for [2Fe–2S] cluster‐containing proteins, whereas that of SLR1417 predominantly showed the presence of the iron ion alone. In the cyanobacterial cell extracts, only SLR1565 was found to form a complex with a novel prokaryotic HEAT‐repeats‐containing protein, SLR1098. Thus, the two cyanobacterial IscA protein homologs exist in distinct molecular states, suggesting different cellular roles for these proteins.
Suppression of cyclooxygenase‐2 gene transcription by humulon of beer hop extract studied with reference to glucocorticoid
Authors: Yamamoto Kei , Wang Jining , Yamamoto Shozo , Tobe Hiroyasu
Published: July 2002

In murine osteoblastic MC3T3‐E1 cells which produced prostaglandin E2 as a bone resorption factor, the cyclooxygenase‐2 induction by tumor necrosis factor α (TNFα) was suppressed by dexamethasone with an IC50 of 1 nM. Humulon isolated from hop extract for beer brewing was reported previously as an inhibitor of bone resorption [Tobe, H. et al. (1997) Biosci. Biotech. Biochem. 61, 158–159]. We showed that the compound suppressed the TNFα‐dependent cyclooxygenase‐2 induction with an IC50 of as low as about 30 nM as demonstrated experimentally by catalytic activity assay, Northern blot analysis and promoter analysis. Reporter gene experiments suggested that humulon blocked the cyclooxygenase‐2 expression mediated by NFκB and NF‐IL6, but the intracellular glucocorticoid receptor was not involved. The catalytic activity of cyclooxygenase‐2 was inhibited by humulon with an IC50 of as high as 1.6 μM. These results showed that humulon suppressed cyclooxygenase‐2 induction at the step of transcription.
STAT signalling in the mature and aging brain
Authors: De‐Fraja Claudio , Conti Luciano , Govoni Stefano , Battaini Fiorenzo , Cattaneo Elena
Published: July 2002

Activation of the Janus kinases (JAK) and signal transducers and activator of transcription (STAT) proteins in response to specific cytokines and growth factors has been investigated primarily in cells of non‐neuronal origin. More recently, the JAKs and the STATs have also been found to be active in the developing and mature brain, providing evidence for important roles played by these molecules in the control of neuronal proliferation, survival and differentiation. Nothing, however, is known about their occurrence and role(s) in the aged brain. We, therefore, investigated the presence of Stat3 and Stat1 in aged‐rat brain, and have found that the Stat3 protein was markedly down regulated with respect to adult tissue, while Stat1 remained invariant. We also investigated the potential role of some growth factors in the activation of the JAK/STAT in mature neurons, exposing primary neuronal cells to ciliary neurotrophic factor (CNTF), basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Besides CNTF, which is known to recruit Stat3, we found that Stat3 was also tyrosine phosphorylated by bFGF. These data are indicative of an important role of Stat3 and Stat1 in regulating the physiological status of mature neurons.
Mathematical Model of the lac Operon: Inducer Exclusion, Catabolite Repression, and Diauxic Growth on Glucose and Lactose
Authors: Wong Patrick , Gladney Stephanie , Keasling J. D.
Published: July 2002

A mathematical model of the lactose (lac) operon was developed to study diauxic growth on glucose and lactose. The model includes catabolite repression, inducer exclusion, lactose hydrolysis to glucose and galactose, and synthesis and degradation of allolactose. Two models for catabolite repression were tested: (i) cyclic AMP (cAMP) synthesis inversely correlated with the external glucose concentration and (ii) synthesis inversely correlated with the glucose transport rate. No significant differences in the two models were observed. In addition to synthesis, degradation and secretion of cAMP were also included in the model. Two models for the phosphorylation of the glucose produced from lactose hydrolysis were also tested: (i) phosphorylation by intracellular hexokinase and (ii) secretion of glucose and subsequent phosphorylation upon transport back into the cell. The latter model resulted in weak catabolite repression when the glucose produced from lactose was transported out of the cell, whereas the former model showed no catabolite repression during growth on lactose. Parameter sensitivity analysis indicates the importance of key parameters to lac operon expression and cell growth: the lactose and allolactose transformation rates by β‐galactosidase and the glucose concentrations that affect catabolite repression and inducer exclusion. Large values of the allolactose hydrolysis rate resulted in low concentrations of allolactose, low‐level expression of the lac operon, and slow growth due to limited import and metabolism of lactose; small values resulted in a high concentration of allolactose, high‐level expression of the lacoperon, and slow growth due to a limiting concentration of glucose 6‐phosphate formed from allolactose. Changes in the rates of all β‐galactosidase‐catalyzed reactions showed similar behavior, but had more drastic effects on the growth rate. Changes in the glucose concentration that inhibited lactose transport could extend or contract the diauxic growth period during growth in the presence of glucose and lactose. Moreover, changes in the glucose concentration that affected catabolite repression affected the cAMP levels and lacoperon expression, but had a lesser effect on the growth rate.
The high-affinity calcium–calmodulin-binding site does not play a role in the modulation of type 1 inositol 1,4,5-trisphosphate receptor function by calcium and calmodulin
Authors: NOSYREVA Elena , MIYAKAWA Tomoya , WANG Zhengnan , GLOUCHANKOVA Lyuba , MIZUSHIMA Akiko , IINO Masamitsu , BEZPROZVANNY Ilya
Published: July 2002

Modulation of the inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3R) by cytosolic calcium (Ca2+) plays an essential role in Ca2+ signalling, but structural determinants and mechanisms responsible for the InsP3R regulation by Ca2+ are poorly understood. In the present study, we expressed rat InsP3R type 1 (InsP3R1) in Spodoptera frugiperda cells using a baculovirus-expression system and reconstituted the recombinant InsP3R1 into planar lipid bilayers for functional analysis. We observed only minor effects of 0.5mM of calmodulin (CaM) antagonist W-7 on the Ca2+ dependence of InsP3R1. Based on a previous analysis of mouse InsP3R1 [Yamada, Miyawaki, Saito, Nakajima, Yamamoto-Hino, Ryo, Furuichi and Mikoshiba (1995) Biochem J. 308, 83–88], we generated the Trp1577→Ala (W1577A) mutant of rat InsP3R1 which lacks the high-affinity Ca2+—CaM-binding site. We found that the W1577A mutant displayed a bell-shaped Ca2+ dependence similar to the wild-type InsP3R1 in planar lipid bilayers. Activation of B cell receptors resulted in identical Ca2+ signals in intact DT40 cells lacking the endogenous InsP3R and transfected with the wild-type InsP3R1 or the W1577A mutant cDNA subcloned into a mammalian expression vector. In the planar lipid bilayer experiments, we showed that both wild-type InsP3R1 and W1577A mutant were equally sensitive to inhibition by exogenous CaM. From these results, we concluded that the interaction of CaM with the high-affinity Ca2+—CaM-binding site in the coupling domain of the InsP3R1 does not play a direct role in biphasic modulation of InsP3R1 by cytosolic Ca2+ or in InsP3R1 inhibition by CaM.
Solution structure and backbone dynamics of human epidermal-type fatty acid-binding protein (E-FABP)
Authors: GUTIÉRREZ-GONZÁLEZ Luis H. , LUDWIG Christian , HOHOFF Carsten , RADEMACHER Martin , HANHOFF Thorsten , RÜTERJANS Heinz , SPENER Friedrich , LÜCKE Christian
Published: July 2002

Human epidermal-type fatty acid-binding protein (E-FABP) belongs to a family of intracellular 14–15kDa lipid-binding proteins, whose functions have been associated with fatty acid signalling, cell growth, regulation and differentiation. As a contribution to understanding the structure—function relationship, we report in the present study features of its solution structure and backbone dynamics determined by NMR spectroscopy. Applying multi-dimensional high-resolution NMR techniques on unlabelled and 15N-enriched recombinant human E-FABP, the 1H and 15N resonance assignments were completed. On the basis of 2008 distance restraints, the three-dimensional solution structure of human E-FABP was subsequently obtained (backbone atom root-mean-square deviation of 0.92±0.11Å; where 1Å = 0.1nm), consisting mainly of 10 anti-parallel β-strands that form a β-barrel structure. 15N relaxation experiments (T1, T2 and heteronuclear nuclear Overhauser effects) at 500, 600 and 800MHz provided information on the internal dynamics of the protein backbone. Nearly all non-terminal backbone amide groups showed order parameters S2>0.8, with an average value of 0.88±0.04, suggesting a uniformly low backbone mobility in the nanosecond-to-picosecond time range. Moreover, hydrogen/deuterium exchange experiments indicated a direct correlation between the stability of the hydrogen-bonding network in the β-sheet structure and the conformational exchange in the millisecond-to-microsecond time range. The features of E-FABP backbone dynamics elaborated in the present study differ markedly from those of the phylogenetically closely related heart-type FABP and the more distantly related ileal lipid-binding protein, implying a strong interdependence with the overall protein stability and possibly also with the ligand-binding affinity for members of the lipid-binding protein family.
Identification, cloning and expression of the mouse N-acetylglutamate synthase gene
Authors: CALDOVIC Ljubica , MORIZONO Hiroki , YU Xiaolin , THOMPSON Mark , SHI Dashuang , GALLEGOS Rene , ALLEWELL Norma M. , MALAMY Michael H. , TUCHMAN Mendel
Published: July 2002

In ureotelic animals, N-acetylglutamate (NAG) is an essential allosteric activator of carbamylphosphate synthetase I (CPSI), the first enzyme in the urea cycle. NAG synthase (NAGS; EC 2.3.1.1) catalyses the formation of NAG from glutamate and acetyl-CoA in liver and intestinal mitochondria. This enzyme is supposed to regulate ureagenesis by producing variable amounts of NAG, thus modulating CPSI activity. Moreover, inherited deficiencies in NAGS have been associated with hyperammonaemia, probably due to the loss of CPSI activity. Although the existence of the NAGS protein in mammals has been known for decades, the gene has remained elusive. We identified the mouse (Mus musculus) and human NAGS genes using their similarity to the respective Neurospora crassa gene. NAGS was cloned from a mouse liver cDNA library and was found to encode a 2.3kb message, highly expressed in liver and small intestine with lower expression levels in kidney, spleen and testis. The deduced amino acid sequence contains a putative mitochondrial targeting signal at the N-terminus. The cDNA sequence complements an argA (NAGS)-deficient Escherichia coli strain, reversing its arginine auxotrophy. His-tagged versions of the pre-protein and two putative mature proteins were each overexpressed in E. coli, and purified to apparent homogeneity by using a nickel-affinity column. The pre-protein and the two putative mature proteins catalysed the NAGS reaction but one of the putative mature enzymes had significantly higher activity than the pre-protein. The addition of l-arginine increased the catalytic activity of the purified recombinant NAGS enzymes by approx. 2–6-fold.
Apolipoprotein E structural requirements for the formation of SDS-stable complexes with β-amyloid-(1–40): the role of salt bridges
Authors: BENTLEY Nicholas M. , LaDU Mary Jo , RAJAN Chandrika , GETZ Godfrey S. , REARDON Catherine A.
Published: July 2002

Of the three major isoforms of human apolipoprotein E (apoE), apoE4 is a risk factor for the development of Alzheimer's disease. Among possible neurologically relevant differences in the properties of apoE3 and apoE4 is the fact that apoE3 forms an SDS-stable complex with β-amyloid-(1–40) (Aβ40) with greater avidity than does apoE4. This interaction may sequester potentially toxic species of Aβ or facilitate clearance. To understand more about this difference, we examined whether differences in salt bridges between apoE domains influence the capacity of apoE isoforms to form complexes with Aβ. In apoE3 there is a salt bridge between Arg-61 and Asp-65, while in apoE4 there are salt bridges between Arg-61 and Glu-255, and Arg-112 and Glu-109. Mutation of position 112, which is Cys in apoE3 and Arg in apoE4, to Ala or Lys abolished complex formation, while mutant apoE with Ser at this position retained the capacity to form complex. Substituting Ala for Glu-109 had no effect on the ability of either apoE4 or apoE3 to form complexes. On the other hand, substitution of Thr for Arg-61 in apoE3 abolished, and truncation of apoE3 at position 201 substantially lowered, but did not abolish, complex formation. Neither of these mutations within apoE4 had any affect on its complex formation with Aβ. These results suggest that the nature of the cysteine residue in apoE3 and interactions between the N-terminal and C-terminal domains of human apoE are important for the ability of apoE3 to form an SDS-stable complex with Aβ40.
Digest
Authors: Castaing D
Published: July 2002

Dr Denis Castaing, Editor of Annales de Chirurgie, chooses the best from issues six and seven of 1997. A reciprocal digest written by our European Editor, Mr Colin Johnson, is published in the French journal.
Sodium fusidate and the cytokine response in an experimental model of acute pancreatitis
Authors: Osman M O , El-Sefi T , Lausten S B , Jacobsen N O , Larsen C G , Jensen S I
Published: July 2002

Background

New therapies designed to downregulate the aberrant immune response associated with severe acute necrotizing pancreatitis (ANP) are being increasingly investigated in different experimental models of ANP. The aim of this study was to test the potential effects of sodium fusidate on the course of severe ANP in rabbits.

Methods

ANP was induced in 20 rabbits by retrograde injection of 5 per cent chenodeoxycholic acid into the pancreatic duct followed by duct ligation. The rabbits were allocated to pretreatment with intravenous physiological saline or sodium fusidate 80 mg/kg 30 min before the induction of ANP. Levels of serum amylase, lipase, tumour necrosis factor (TNF) α, interleukin (IL) 8, glucose and calcium, and leucocyte count were measured every 3 h for a total of 12 h. At the end of the experiment, ascitic fluid was collected and the pancreatic, lung and kidney tissues were obtained for histological examination.

Results

Pretreatment with sodium fusidate reduced the mortality rate from six of ten to three of ten (P < 0·05) and reduced the output of ascitic fluid from 5·2 to 2·0 ml/h (P <0·001). Serum levels of TNF-α and IL-8 were reduced significantly in the treated group from 5 min up to 9 h after induction of ANP. The leucopenia observed after 3 h in the untreated group was not significantly improved in the group treated with sodium fusidate (P = 0·055). By contrast, both treated and untreated rabbits had similar biochemical changes including levels of amylase, lipase, glucose and calcium as well as similar histological changes in the pancreas and lungs.

Conclusion

Pretreatment with sodium fusidate resulted in a considerable reduction in mortality rate and ascitic fluid output in rabbits with bile-induced ANP, probably by lowering the TNF-α and IL-8 blood levels. However, pretreatment with sodium fusidate did not alter the local or systemic manifestations of ANP. Thus, cytokines other than TNF-α and IL-8 are likely to mediate the local and systemic symptoms of ANP.
Book reviews
Authors: Smith J A R , Baxter J N
Published: July 2002

Applied Surgical Anatomy – A Guide for the Surgical Trainee

M. A. Glasby, W. J. Owen and F. Kristmundsdottir (eds) 252 × 192 mm. Pp. 299. Illustrated. 1998. Oxford: Butterworth-Heinemann. £49.50.

A Guide to Laparoscopic Surgery

A. Najmaldin and P. Guillou 233 × 154 mm. Pp. 169. Illustrated. 1998. Oxford: Blackwell Science. £24.95.
A hernia sac cannot be found at operation
Authors: Waters K J
Published: July 2002

During an attempt to repair an inguinal hernia difficulty is encountered in finding the sac. How should such a situation be handled? Mr Kenneth Waters of London replies.
Electronic evaluation of the value of double gloving
Authors: Caillot J-L , Côte C , Abidi H , Fabry J
Published: July 2002

Background

Breakdown of the surgeon–patient barrier represents a risk for transmission of infectious disease. Such breakdowns are frequently not recognized by the surgical team. The protection afforded by double gloving under normal operating conditions was evaluated.

Methods

An electronic device detected breakdown of the surgeon–patient barrier in a series of 80 surgical procedures, randomly assigned to either double or single gloving. Fluid contact due to glove perforation, porosity or gown wetting was recorded during 151 individual surgeon episodes covering 238 operator-hours. Surgical procedures were called superficial for incisions of less than 10 cm.

Results

Double gloving reduced the number of perforation and porosity alarms twofold in both superficial and deep surgical procedures. Deep procedures carried a sevenfold increased risk of barrier breakdown compared with superficial procedures, the risk being greatest for the principal operator.

Conclusion

Without electronic detection, a large majority of barrier breakdowns would remain undetected by the surgical team and lead to prolonged contact with potentially contaminating body fluids. The use of double gloving provides real protection against such contamination risks.
Surgical management of polypoid lesions of the gallbladder
Authors: Mainprize K S , Gould S W T , Gilbert J M
Published: July 2002

Background

With improvements in ultrasonography more polypoid lesions of the gallbladder (PLGs) are being detected. The management of these is controversial.

Methods

The demographic, radiological and pathological data of 38 patients with ultrasonographically detected PLGs were reviewed. A Medline search for such lesions was performed and a review of the literature is presented.

Results

Thirty-four patients underwent cholecystectomy and four were advised against or declined operation. Of the 34 who had cholecystectomy, 11 had macroscopic and histopathologically proven PLGs. Of these, seven had cholesterol polyps, two had adenomas, one had a carcinoid tumour and one had an adenocarcinoma of the gallbladder. One patient had a histopathologically normal gallbladder. The remainder had chronic cholecystitis with or without gallstones. All of the patients with neoplastic lesions of the gallbladder had solitary polyps greater than 1·0 cm in diameter.

Conclusion

A protocol for the management of ultrasonographically detected PLGs is proposed. In this protocol it is suggested that patients with a PLG should undergo surgery if they are symptomatic, or if the PLG is 1·0 cm or more in diameter.
Long-term symptomatic follow-up after Lind fundoplication
Authors: Cameron I C , Stoddard J E , Treacy P J , Patterson J , Stoddard C J
Published: July 2002

Aims

Few published studies have detailed the long-term results of antireflux surgery. The aim of this study was to assess the long-term success of open Lind fundoplication in controlling the symptoms of gastro-oesophageal reflux disease.

Methods

One hundred and thirty-two patients with reflux symptoms underwent a primary Lind fundoplication between April 1986 and February 1994; all operations were supervised or performed by one surgeon. The median age at operation was 47 (range 17–77) years. All patients attended for follow-up in the early postoperative period. It was possible to conduct a telephone interview to assess long-term symptom control, at a median time of 9·5 (range 5–13) years following operation, in 112 of the 124 patients who were still alive.

Results

Ninety-one patients underwent oesophageal pH studies before and soon after operation. The oesophageal pH was less than 4 for a mean 14·9 per cent of the time before operation, falling to 2·4 per cent in the early postoperative period (P < 0·001, Wilcoxon test). At early postoperative assessment, two patients complained of mild reflux symptoms and 44 (33 per cent) complained of postfundoplication symptoms (dysphagia, epigastric bloating and early satiety). At telephone interview, 106 patients (95 per cent) were symptom free with regard to heartburn and regurgitation. Six patients have developed recurrent reflux symptoms, in four of whom symptoms are controlled by a proton pump inhibitor. Two patients have required further antireflux surgery, one within 2 months of the first procedure for severe dysphagia and the other for recurrent reflux. Significant postfundoplication symptoms persist (dysphagia with or without gas bloat) in three patients (3 per cent).

Conclusions

Open Lind fundoplication appears to be effective in the long-term control of gastro-oesophageal reflux in 95 per cent of patients and represents a standard against which the long-term results of laparoscopic surgery will need to be compared.
Angiographic embolization for major haemorrhage after upper gastrointestinal surgery
Authors: Beattie G C , MacDonald A , Powell J J , Redhead D , Siriwardena A K
Published: July 2002

Aims

Severe postoperative haemorrhage after upper gastrointestinal surgery is a serious complication. This study examined the effectiveness of selective mesenteric angiography (SMA) in localizing a bleeding point and the ability of angiographic haemostatic methods to control bleeding.

Methods

The case notes of a consecutive series of nine patients undergoing urgent SMA during 1996–1998 were analysed. Examination of angiography suite records confirmed the accuracy of patient identification. SMA was performed 18 times with 13 embolizations in nine individuals (seven men; median age 54 (27–73) years). Patients underwent the following operations: Whipple pancreaticoduodenectomy (four patients), pancreatic necrosectomy (two), total gastrectomy (one), cholecystectomy (one) and splenectomy (one). The median interval from surgery to haemorrhage was 15 (2–49) days. Six patients presented with haematemesis/melaena and three with bleeding from drains. Seven had evidence of shock (systolic blood pressure less than 100 mmHg, pulse more than 100 per min); the mean preprocedure haemoglobin concentration was 59 g/l. A median of 8 (4–14) units of blood were transfused before embolization and 4 (2–9) units after. Ten initial endoscopies were performed in six patients, seven of which revealed a source of bleeding. Endoscopic haemostasis was attempted in five and achieved temporary control of bleeding in two.

Results

Angiography revealed a discrete bleeding point in 13 of 18 procedures in eight patients. Where a bleeding point was identified, angiographic embolization using 3–8-mm stainless steel coils (ten) or a combination of coils and gelatin sponge (three) achieved radiological evidence of haemostasis in all cases. Periprocedural complications occurred in one patient with unintentional partial embolization of the right hepatic artery during embolization of an actively bleeding left hepatic artery pseudoaneurysm. Rebleeding occurred in six patients within 48 h. Three rebleeds were successfully managed with repeat SMA and embolization (one patient required a third embolization); the remaining three required surgery. Definitive radiological haemostasis was achieved in six patients. Five of the nine patients died in hospital, two of whom had been successfully embolized.

Conclusions

In this group of patients, endoscopy contributed relatively little to treatment of postoperative haemorrhage. In contrast, SMA identified a bleeding point in eight of nine patients and achieved definitive control of bleeding in six. SMA and embolization appears to have a useful role in patients with this infrequent but potentially lethal complication.
Achalasia: management, outcome and surveillance in a specialist unit
Authors: Harris A M , Dresner S M , Griffin S M
Published: July 2002

Aims

The management and surveillance of achalasia remains controversial at the present time. The aim of this study was therefore to evaluate the results of endoscopic management and subsequent surveillance of patients with achalasia presenting to a specialist unit.

Methods

A prospective cohort of 40 patients with a radiological and manometric diagnosis of achalasia who presented to this unit between 1991 and 1998 were studied; the male: female ratio was 1: 1 and the median age 38 (range 15–84) years. Twenty-one patients presented de novo, seven had previously undergone cardiomyotomy and 12 were referred following unsuccessful dilatation.

Results

Some 36 patients were treated with balloon dilatation (Microvasive achalasia balloon, 35/40 mm). Results were graded 1–4 (1, asymptomatic; 2, symptomatic but significantly improved; 3, symptomatic with no change; and 4, symptomatic but worse); 29 of 36 patients were grade 1 at subsequent follow-up and the remaining seven were grade 2 (median follow-up 17 (range 5–96) months). There was a single complication of oesophageal perforation which was treated conservatively with full recovery. Following intervention, patients were enrolled in a prospective surveillance programme of chromoendoscopy at 2-year intervals; in a total of 74 patient-years' follow-up, two superficial squamous cell carcinomas (SCCs) and one adenocarcinoma (following cardiomyotomy) were detected, giving a relative risk of one cancer in 25 patient-years.

Conclusions

Balloon dilatation is a safe and effective treatment for achalasia even in patients who have had previous unsuccessful dilatations or cardiomyotomy. There is a high risk of SCC and the adenocarcinoma may have resulted from previous refluxogenic therapy, so all patients with achalasia should be followed up with surveillance endoscopy.
Belching and bloating: facts and fantasy after antireflux surgery
Authors: Tew S , Ackroyd R , Jamieson G G , Holloway R H
Published: July 2002

Background

Fundoplication is commonly complicated by belching difficulty and abdominal bloating. Postoperative belching ability, however, is difficult to assess; subjective patient reporting is often used but may be unreliable. Manometric measurement of the gastro-oesophageal ‘common cavity’ is an objective marker of gastro-oesophageal gas reflux.

Methods

Twenty patients who had undergone Nissen fundoplication and 11 healthy controls underwent oesophageal manometry at rest and during gastric distension for 10 min with 750 ml of gas.

Results

Half of the patients reported an inability to belch; the other half reported varying degrees of belching difficulty, most of whom were rarely able to relieve bloating by belching. During gastric distension, none of the patients had transient lower oesophageal sphincter relaxation, while the controls had a median of 1 (range 0–1). Patients had fewer common cavities than controls; however, none of the belch urges experienced during gastric distension in patients was associated with a common cavity, compared with 48 per cent in controls.

Conclusion

After fundoplication, patients do not belch as a result of gastro-oesophageal gas reflux; rather it may be due to oesophagopharyngeal reflux of swallowed air. Subjective reporting of belching ability is inaccurate and manometric measurement of common cavities provides a better means of assessment.
Lower limb ulceration: a detailed study of aetiology in 555 patients
Authors: Naik J , Bello A M , Scriven J M , Hartshorne T , London N J M
Published: July 2002

Background

The purpose of the study was to investigate the aetiology of lower limb ulceration.

Methods

The aetiology of lower limb ulceration was reviewed in 555 patients with 689 ulcerated limbs referred to a single-visit leg ulcer clinic.

Results

The mean age of the patients was 70 (range 27–95) years and 335 (60 per cent) were women. The aetiology of the ulceration in 689 limbs was venous in 496 (72 per cent), arterial in 14 (2 per cent), mixed venous and arterial in 101 (15 per cent), with other causes in 78 (11 per cent). Of the 496 venous ulcers, 261 (53 per cent) had isolated superficial reflux, 233 (47 per cent) had deep venous reflux, of which 165 (71 per cent) had full-length and 68 (29 per cent) segmental reflux, and two patients had isolated perforator reflux. Deep venous obstruction was present in 16 limbs (3 per cent) with venous ulcers and 14 of these demonstrated continuous flow in the long saphenous vein (LSV). Of the 261 ulcerated legs with isolated superficial reflux, 197 (75 per cent) had LSV reflux only, 22 (8 per cent) had short saphenous vein (SSV) reflux only and 41 (16 per cent) had combined LSV and SSV reflux. Of those with LSV reflux, 65 per cent had a medial malleolar ulcer and 20 per cent had a lateral malleolar lesion. Of those with SSV reflux, 62 per cent had a lateral malleolar ulcer and 38 per cent had a medial malleolar ulcer.

Conclusion

Half of the ulcerated legs have superficial venous reflux; these combined with the superficial and segmental deep venous reflux group comprise the 65 per cent of patients who may benefit from superficial venous surgery. Continuous flow in the LSV should alert the clinician to deep venous obstruction, in which circumstance compression therapy should be used with extreme caution. Duplex is central to the investigation of the ulcerated leg.
Decreased endothelin binding and receptor density in varicose veins
Authors: Agu O , Atwal A , Dashwood M , Hamilton G , Baker D M
Published: July 2002

Background

The primary cause of venodilatation and reduced contractility in varicose veins is unclear. Endothelin (ET) 1 acts on smooth muscle cell ET A/ET B receptors to induce contraction and growth, and on endothelial cells to induce production of the vasorelaxant and growth inhibitors nitric oxide and prostacyclin. These factors may be involved in the aetiology of varicose veins. This study investigated ET-1 binding and ET A/ET B receptor density in varicose and non-varicose veins.

Methods

Proximal long sapheous vein (LSV) sections from nine patients undergoing surgery for varicose veins were compared with normal LSV from nine patients undergoing coronary artery bypass surgery. Slide-mounted sections were incubated in [125I]-radiolabelled ET-1 and ET A/ET B binding sites were identified using subtype-selective radioligands. Receptor density and distribution was quantified on autoradiographs by densitometry and binding was localized at the cellular level by nuclear emulsion.

Results

ET-1 binding and ET B receptor density decreased significantly in the varicose group. There was no significant difference in ET A receptor density.

Conclusion

Decreased ET-1 binding may contribute to venodilatation and poor contractility in varicose veins. This may be due to decreased tunica media ET B receptor density.
Durability of angioplasty in treating severe leg ischaemia
Authors: Molloy K , Nasim A , London N J M , Naylor A R , Bell P R F , Fishwick G , Bolia A , Thompson M M
Published: July 2002

Background

Percutaneous transluminal angioplasty (PTA) has recently been accepted as a valuable therapeutic option in patients with severe limb ischaemia. However, despite the increasing use of this technique, there have been concerns that the long-term efficacy of PTA is inferior to that of surgical revascularization. This prospective study reports the outcome of an unselected cohort of patients who underwent balloon angioplasty for severe lower limb ischaemia in a single centre.

Methods

During 1997, 108 patients with 133 severely ischaemic legs were treated by PTA. The median age of the patients (49 per cent men) was 76 years. Symptoms were rest pain in 31 per cent, ischaemic ulceration in 56 per cent and gangrene in 13 per cent. The distribution of risk factors was typical: diabetes 32 per cent, ischaemic heart disease 18 per cent and stroke 16 per cent. Median (interquartile range) follow-up was 16 (12–19) months. There was a mean of 1·7 angioplasty sites per patient, distributed in the iliofemoral (14 per cent), superficial femoral (42 per cent), popliteal (18 per cent) and crural (26 per cent) arteries. PTA was performed luminally in 20 per cent of cases and subintimally in the remainder. Overall, 67 per cent of the lesions were complete occlusions with a median length of 20 (10–40) cm.

Results

Technical success was achieved in 104 limbs, with 29 failures. The outcome of patients with a failed angioplasty (29) was poor, with 14 requiring bypass surgery, 11 undergoing a major amputation and 32 per cent dying after the procedure. In contrast, patients having a technically successful angioplasty had a good outcome after a median follow-up of 16 (12–19) months. In this group there was a 30 per cent overall mortality rate during follow-up. However, 85 per cent of the patients had no symptoms of critical ischaemia and the limb salvage rate was 92 per cent.

Conclusion

PTA is an effective and durable procedure in patients with critical leg ischaemia, with results comparable to those of historical surgical controls. Technical failure of PTA is, however, associated with a dire outcome.
Dextran-40 stimulates resting platelets and binds more avidly to activated platelets
Authors: Hayes P D , Box H , Tull S , Bell P R F , Goodall A H , Naylor A R
Published: July 2002

Background

A programme of monitoring and treatment with low-dose 10 per cent Dextran-40 (20 ml h−1) can successfully prevent thrombotic occlusion of the carotid artery after endarterectomy. This is a clinically effective treatment, over 500 CEAs have been performed with no thrombotic strokes, but little is known about the mechanism by which low-dose Dextran-40 affects platelet-rich thrombus formation.

Methods

In study 1, platelets from ten patients undergoing CEA were collected in a standardized manner. The response to therapeutic doses of Dextran-40 was assessed in vitro using whole-blood flow cytometric analysis of fibrinogen binding in response to adenosine 5′-diphosphate (ADP) and thrombin. Platelet aggregation in response to ADP and collagen was recorded. In study 2, blood collected from ten normal subjects was incubated with fluorescently labelled Dextran-40 and binding was measured using flow cytometry. In these experiments blood was either first incubated for 10 min with the FITC–Dextran-40 and then activated with thrombin 0·4 units ml−1 or activated with thrombin 0·4 units ml−1 for 10 min before incubation with FITC–Dextran-40.

Results

In study 1, reincubation of the patients' blood with Dextran-40 increased fibrinogen binding to resting platelets by 352 per cent (P < 0·05) and to ADP-stimulated platelets by 39 per cent (P < 0·05). Dextran-40 also increased fibrinogen binding in response to thrombin although this difference was not significant (P = 0·12), and increased platelet aggregation in response to ADP (48 per cent) and collagen (32 per cent) (P < 0·05 for both). In study 2, fluorescently labelled Dextran-40 bound to the surface of resting platelets from normal subjects in a dose-dependent manner, and caused platelet activation, as measured by increased P-selectin expression. Incubation with Dextran followed by activation caused a 28 per cent increase in Dextran binding; however, if the platelets were activated first and then exposed to Dextran the binding increased 94 per cent (P = 0·001).

Conclusion

Low-dose Dextran-40 is very effective in preventing thromboembolic complications after CEA. However, in vitro, Dextran-40 has a direct stimulatory effect on platelets. Dextran-40 binds to platelets and shows preferential binding to activated, compared with resting, platelets. Dextran may exert a beneficial antiplatelet/antithrombotic effect in vivo by inhibiting the recruitment of activated platelets to a growing thrombus.
Clinical governance and the vascular surgeon
Authors: Irvine C , Grayson D , Lusby R J
Published: July 2002

Background

Monitoring of surgeons and their results is currently in question. The validity and the practicality of audit to determine substandard results is undetermined. To test the instrument of audit, statistical modelling was applied to two indicator vascular procedures, elective abdominal aortic aneurysm (AAA) repair and carotid endarterectomy (CEA), with accepted adverse event rates.

Methods

Binomial statistical models for varying adverse event rates were constructed. A power calculation was used in an attempt to predict the case numbers required to determine substandard results for individual surgeons and vascular units. Statistical conventions of power (80 per cent) and upper criterion of rarity (0·05) were used. Previous activity rates for CEA and elective AAA repair were used to predict the time taken to gather these data.

Results

Base rates of 3 and 6 per cent were considered, along with a range of alternate practice. Number of adverse events, number of operations to be studied and the time that this would take are shown in the Table.

Conclusion

Statistical modelling demands assumptions about accepted adverse event rates, confidence criteria and what constitutes substandard results. Large numbers of patient data are required even for common operations with accepted adverse event rates. These data raise serious questions as to the feasibility of performing clinical governance on the basis of crude morbidity and mortality event rates alone.
Effect of chronic renal failure on postoperative mortality rate following arterial reconstruction
Authors: Ray S A , Keast-Butler O D , Wood C M , Scoble J E , Taylor P R
Published: July 2002

Background

Chronic renal failure (CRF) is both a risk factor for, and a consequence of, peripheral arterial disease. There is also increasing evidence that patients with CRF have a higher mortality rate following arterial reconstruction, but it is not known whether this is different for aneurysmal or occlusive disease.

Methods

Over 8 years 1718 consecutive arterial reconstructions performed under the care of one consultant were studied prospectively. Patients were defined as having CRF if at the time of surgery the serum creatinine measured more than 400 μmol 1−1, they were undergoing dialysis or they had received a renal transplant. The in-hospital postoperative mortality rate was compared between patients with and without CRF and analysed according to the urgency as well as the type of arterial reconstruction.

Results

Sixty-nine patients (4 per cent) undergoing arterial reconstruction over the study period were defined as having CRF. Sixteen (23 per cent) of these died following surgery (myocardial infarct seven, multiple organ failure three, stroke one, mesenteric thrombosis one, paraplegia one, respiratory failure one, pneumonia one, failure to thrive one), in comparison to 120 (7·3 per cent) of 1649 patients without CRF. The mortality rate in patients with CRF was highest in those who underwent urgent/emergency surgery and those who had reconstruction for occlusive disease.

Conclusion

Patients with CRF have a threefold increase in mortality rate following arterial reconstruction. Patients undergoing infrainguinal bypass are at particular risk and should be carefully selected and counselled.
Prevalence of popliteal aneurysm in patients with abdominal aortic aneurysm or intermittent claudication
Authors: Phillips D , Hussain S T , Minor J , Collin J
Published: July 2002

Background

The prevalence of abdominal aortic aneurysm (AAA) in defined risk groups has been well established but the prevalence of popliteal artery aneurysm is unknown. The aim was to discover the prevalence of popliteal artery aneurysm in patients with known AAA and in patients attending a vascular clinic with intermittent claudication (IC).

Methods

The maximum anterior posterior diameter of the popliteal artery was measured by duplex sonography in 200 patients with known AAA attending an established surveillance programme and 325 patients with IC but no aortic aneurysm attending a vascular clinic. In all patients sex, age and height were recorded.

Results

Conclusion

The prevalence of popliteal aneurysm is 2·0 (confidence interval 0–3·9) per cent in patients with AAA and 0·6 (0·2–1·4) per cent in patients with IC. Compared with claudicants, patients with AAA are significantly older and taller, more likely to be men and have larger popliteal arteries. The prevalence of popliteal aneurysm is too low, even in suspected high-risk groups, for screening to be worthwhile.
RETA: update on the short-term (30 day) and long-term (1 and 2 years) results of endovascular repair of abdominal aortic aneurysms
Authors: Thomas S M , Gaines P A , Beard J D
Published: July 2002

Background

The updated results from the Registry of Endovascular Treatment of Aneurysms (RETA) for short- and long term outcomes from 3 years of data collection are presented.

Methods

Some 611 patients were submitted to RETA from January 1996 to December 1999 from 31 centres. In the same period 1-year follow-up was received for 299 of the 340 cases requested (88 per cent return rate) and 2-year follow-up for 88 of the 155 cases requested (57 per cent return rate).

Results

At 30 days 90 per cent of abdominal aortic aneurysms (AAA) were excluded. The rate of conversion to open repair was 5 per cent. Complications occurred in 25 per cent of patients. The overall 30-day mortality rate was 7 per cent with significantly more deaths in the aortouni-iliac and crossover groups (12 versus 4 per cent; adjusted odds ratio (OR) 2·6 (95 per cent confidence interval (c.i.) 1·2–5·9); P = 0·018), in unfit patients (18 versus 4 per cent; adjusted OR 4·3 (95 per cent c.i. 2·0–9·5); P < 0·001) and in patients with larger aneurysms (10 versus 2 per cent; adjusted OR 4·4 (95 per cent c.i. 1·4–13); P = 0·009). At 1 year the mortality rate was 11 per cent, with four deaths (1 per cent) due to ruptured AAA. New complications were reported in 53 patients (20 per cent) with 31 (12 per cent) related to the device or AAA. In the second year of follow-up the mortality rate was 11 per cent with one death (1 per cent) due to ruptured AAA. New complications in the second year after device placement were reported in 24 per cent of patients, with 16 (20 per cent) related to the device or AAA. The cumulative endoleak-free survival for all patients was 57 per cent at 2 years.

Conclusion

The 30-day mortality rate for endovascular repair was comparable to reported results for conventional surgery, particularly in fit patients. There was a relatively high complication rate at follow-up, with ruptures reported. Most complications had endovascular treatment.
Infrainguinal bypass grafting for critical ischaemia in the hands of trainees
Authors: Papp L , Evans S M , Kelman J , Chalmers R T A , Murie J A , Bradbury A W
Published: July 2002

Background

Changes in surgical training mean that operative experience must be gained more efficiently. However, it is important to demonstrate that increasing training opportunities are not associated with inferior patient outcome. The immediate and long-term outcomes of patients undergoing infrainguinal bypass surgery by consultants and trainees were compared.

Methods

A prospectively gathered database of 1077 infrainguinal bypasses performed on 1003 patients for chronic critical limb ischaemia between 1 January 1983 and 31 December 1998 in a single regional vascular unit was evaluated.

Results

Consultants performed 733 operations (68·1 per cent), 347 (47·3 per cent) above-knee, 257 (35·1 per cent) below-knee popliteal, 121 (16·5 per cent) crural and eight (1·1 per cent) other procedures. Of 344 trainee operations, 170 (49·4 per cent) were above-knee, 122 (35·5 per cent) below-knee, 48 (14·0 per cent) crural and four (1·2 per cent) other operations. There was no significant difference in 30-day mortality rate between consultant (2·8 per cent) and trainee (2·0 per cent) operations, nor was there any significant difference in patency or limb salvage rates at 36 months (Table). There was a trend towards reduced graft patency in trainee crural bypasses but this was not statistically significant (35·9 versus 56·2 per cent; P = 0·14, log rank test).

Conclusion

These data suggest that, with appropriate case selection and supervision, training in femoropopliteal and crural bypass grafting does not compromise early or long-term outcome.