A survey of patient informational preferences when choosing between medical and surgical therapy for ulcerative colitis: a sub-study from the DISCUSS project.

AIM: People living with ulcerative colitis (UC) have two broad treatment avenues, namely medical or surgical therapy. The choice between these can depend on patient preference as well as the receipt of relevant information. The aim of this study was to define the informational needs of patients with UC. METHOD: A postal survey was designed to capture respondent demographics, treatment experienced within the previous 12 months and informational preferences by rating a long list of items. It was delivered through two hospitals that provide tertiary inflammatory bowel disease services. Descriptive analyses were performed to describe demographics and experiences. Principal component analysis was carried out using a varimax rotation to investigate informational needs. RESULTS: A total of 101 responses were returned (20.1% response rate). The median age of respondents was 45 years and the median time since diagnosis was 10 years. Control preferences skewed towards shared (42.6%) or patient-led but clinician-informed (35.6%). Decision regret was low for the population (median 12.5/100, range 0-100). Key informational needs related to medical therapy were benefits and risks of long-term therapy, burden of hospital attendance, reproductive health, need for steroid treatment and impact on personal life. For surgery, these were stoma information, effect on daily life, effect on sexual and reproductive health, risks and benefits and disruption of life due to surgery. CONCLUSION: This study has identified key areas for discussion when counselling patients about treatment decisions around medical therapy and surgery for UC.

A systematic review and meta-analysis of outcomes after elective surgery for ulcerative colitis.

AIM: Approximately 20%-30% of patients with ulcerative colitis (UC) will undergo surgery during their disease course, the vast majority being elective due to chronic refractory disease. The risks of elective surgery are reported variably. The aim of this systematic review and meta-analysis is to summarize the outcomes after elective surgery for UC. METHODS: A systematic review was conducted that analysed studies reporting outcomes for elective surgery in the modern era (>2002). It was prospectively registered on the PROSPERO database (ref: CRD42018115513). Searches were performed of Embase and MEDLINE on 15 January 2019. Outcomes were split by operation performed. Primary outcome was quality of life; secondary outcomes were early, late and functional outcomes after surgery. Outcomes reported in five or more studies underwent a meta-analysis of incidence using random effects. Heterogeneity is reported with I2 , and publication bias was assessed using Doi plots and the Luis Furuya-Kanamori index. RESULTS: A total of 34 studies were included (11 774 patients). Quality of life was reported in 12 studies, with variable and contrasting results. Thirteen outcomes (eight early surgical complications, five functional outcomes) were included in the formal meta-analysis, all of which were outcomes for ileal pouch-anal anastomosis (IPAA). A further 71 outcomes were reported (50 IPAA, 21 end ileostomy). Only 14 of 84 outcomes received formal definitions, with high inter-study variation of definitions. CONCLUSION: Outcomes after elective surgery for UC are variably defined. This systematic review and meta-analysis highlights the range of reported incidences and provides practical information that facilitates shared decision making in clinical practice.

YouTube™ as a source of information for patients undergoing laryngectomy: a thematic analysis.

PURPOSE: Total laryngectomy and end tracheal stoma formation are often required to treat advanced laryngeal cancer. Resources on the internet are commonly accessed by patients as a source of healthcare information. YouTube™, the most popular video-hosting website, is one such resource. The aims of this study were to assess the thematic content of the most viewed YouTube™ videos concerning laryngectomy for laryngeal cancer and to evaluate user response to these videos. METHOD: A search of YouTube™ was performed and data were extracted from videos with > 100 views. Upload source, number of views, likes, dislikes and comments were collected and the content of comments was analysed. User response was compared between upload sources using Kruskal-Wallis testing. Inductive thematic analysis of video content was performed to identify overarching themes and subthemes. RESULTS: A total of 96 videos were identified, 16 uploaded by patients, 24 by individual healthcare professionals and 56 by professional healthcare institutions. There were 1214,503 views and no significant differences in the number of views, likes or dislikes between upload sources. Three overarching themes and 17 subthemes were identified. Comments were most frequently characterised as offering praise. CONCLUSION: YouTube™ has been shown to be a popular platform for sharing information about laryngectomy for laryngeal cancer. There is a lack of data concerning the quality of this information, however, and future work should focus on assessing this. Trusted institutions could make use of this medium to disseminate high-quality information to their patients, and to the wider public.

The assessment of online health videos for surgery in Crohn's disease.

AIM: YouTube™ is an open-access, nonpeer-reviewed video-hosting site and is used as a source of publicly available healthcare information. This study aimed to assess the thematic content of the most viewed videos relating to surgery and Crohn's disease and to explore the viewer interactions with these videos. METHOD: A search of YouTube™ was carried out using one search string. The 50 most viewed videos were identified and categorized by source and content themes and assessed for viewer interactions. Video comments were used to describe the usefulness of the video content to viewers. RESULTS: The majority of videos were uploaded by patients (n = 21).The remainder were uploaded by individual healthcare professionals (n = 9), hospital/speciality associations (n = 18) and industry (n = 2). The median number of likes for patient videos was significantly higher than for hospital/speciality association videos (P < 0.001). Patient videos received more comments praising the video content (n = 27) and more comments asking for further information (n = 14). The median number of likes for 'experience of surgery' (P < 0.001) and 'experience of disease' (P = 0.0015) themed videos were significantly higher than for 'disease management' themed videos. CONCLUSION: Crohn's disease patients use YouTube™ as a surgical information source. The content of patient-sourced videos focused on surgical and disease experience, suggesting that these themes are important to patients. Current patient developed videos provide limited information, as reflected by viewers requesting further information. Storytelling patient-centred videos combined with clinical evidence may be a good model for future videos.

A systematic review of online resources to support patient decision-making for full-thickness rectal prolapse surgery.

BACKGROUND: The internet is becoming an increasingly popular resource to support patient decision-making outside of the clinical encounter. The quality of online health information is variable and largely unregulated. The aim of this study was to assess the quality of online resources to support patient decision-making for full-thickness rectal prolapse surgery. METHODS: This systematic review was registered on the PROSPERO database (CRD42017058319). Searches were performed on Google and specialist decision aid repositories using a pre-defined search strategy. Sources were analysed according to three measures: (1) their readability using the Flesch-Kincaid Reading Ease score, (2) DISCERN score and (3) International Patient Decision Aids Standards (IPDAS) minimum standards criteria score (IPDASi, v4.0). RESULTS: Overall, 95 sources were from Google and the specialist decision aid repositories. There were 53 duplicates removed, and 18 sources did not meet the pre-defined eligibility criteria, leaving 24 sources included in the full-text analysis. The mean Flesch-Kincaid Reading Ease score was higher than recommended for patient education materials (48.8 ± 15.6, range 25.2-85.3). Overall quality of sources supporting patient decision-making for full-thickness rectal prolapse surgery was poor (median DISCERN score 1/5 ± 1.18, range 1-5). No sources met minimum decision-making standards (median IPDASi score 5/12 ± 2.01, range 1-8). CONCLUSIONS: Currently, easily accessible online health information to support patient decision-making for rectal surgery is of poor quality, difficult to read and does not support shared decision-making. It is recommended that professional bodies and medical professionals seek to develop decision aids to support decision-making for full-thickness rectal prolapse surgery.

Assessing internet-based information used to aid patient decision-making about surgery for perianal Crohn's fistula.

BACKGROUND: Decision-making in perianal Crohn's fistula (pCD) is preference sensitive. Patients use the internet to access healthcare information. The aim of this study was to assess the online information and patient decision aids relating to surgery for pCD. METHODS: A search of Google™ and the Decision Aids Library Inventory (DALI) was performed using a predefined search strategy. Patient-focussed sources providing information about pCD surgery were included in the analysis. Written health information was assessed using the International Patient Decision Aids Standards (IPDAS) and DISCERN criteria. The readability of the source content was assessed using the Flesch-Kincaid score. RESULTS: Of the 201 sources found, 187 were excluded, leaving 14 sources for analysis. Three sources were dedicated to pCD, and six sources mentioned pCD-specific outcomes. The most common surgical intervention reported was seton insertion (n = 13). The least common surgical intervention reported was proctectomy (n = 1). The mean IPDAS and DISCERN scores were 4.43 ± 1.65 out of 12 (range = 2-8) and 2.93 ± 0.73 out of 5 (range = 1-5), respectively. The mean reading ease was US college standard. CONCLUSIONS: We found no patient decision aids relating to surgery for pCD. The online sources relating to surgery for pCD are few, and their quality is poor, as seen in the low IPDAS and DISCERN scores. Less than half of the sources mentioned pCD-specific outcomes, and three sources were solely dedicated to providing information on pCD. Healthcare professionals should look to create a patient tool to assist decision-making in pCD.

Treatment of primary hyperhidrosis with oral anticholinergic medications: a systematic review.

Primary hyperhidrosis is a condition characterized by excessive sweating. Patients are treated off-license with oral anticholinergic medications and report adverse events associated with systemic anticholinergic interactions. This review assesses clinical evidence of efficacy, impact on quality of life and adverse events associated with oral anticholinergic therapy for primary hyperhidrosis. PRISMA guidelines were implemented to complete a systematic review (PROSPERO:CRD42016036326). MEDLINE, EMBASE and PubMed were searched from 1946 to 2015. Inclusion criteria included observational and experimental studies, anticholinergic medication use in primary hyperhidrosis, oral therapy and clear diagnostic and outcome measures. Twenty-three articles relevant to the inclusion criteria were analysed. Oxybutynin therapy improved symptoms in an average of 76.2% (range 60-97%) patients and improved QOL in 75.6% (range 57.6-100%) of patients. Methantheline bromide therapy was associated with a 41% reduction in axillary sweating, 16.4% reduction in palmar sweating, 25% decrease in HDSS score and 40.9% increase in DLQI score. Outcome measures of glycopyrrolate therapy were too variable to collate. Dry mouth was reported in 73.4% (range 43.3-100%) of participants taking oxybutynin 10 mg/day, 38.6% (range 27.8-63.2%) of patients taking glycopyrrolate and 68.8% of patients taking methantheline bromide. Nine studies reported that patients stopped therapy due to adverse events. In eight of these studies, a mean of 10.9% of total participants ceased treatment due to dry mouth. Evidence of oral anticholinergic therapy for hyperhidrosis is limited. However, its use is associated with improvement in quality of life and clinical symptoms but at the cost of considerable adverse events.

Topical glycopyrrolate reduces axillary hyperhidrosis.

INTRODUCTION: Oral anti-cholinergic medications reduce generalized hyperhidrosis, but the effectiveness of topical anticholinergic solutions on axillary hyperhidrosis is unclear. This study determines the initial effectiveness of 1% and 2% topical glycopyrrolate spray and compares this with Botulinum toxin type A injections for the management of axillary hyperhidrosis. METHODS: In a non-randomized, consecutive patient, prospective questionnaire, treatment comparison study, 40 patients with axillary hyperhidrosis were allocated to one of four study groups (10 patients to each group): (a) 1% glycopyrrolate spray, (b) 2% glycopyrrolate spray, (c) subcutaneous Botulinum toxin type A injections, (d) no treatment. Clinical outcomes were measured by comparing a prospectively administered questionnaire, completed both pre-treatment and 6 weeks after starting treatment. Forty healthy volunteers without axillary hyperhidrosis completed the same questionnaire. RESULTS: The three treatment groups showed a significant (P < 0.05) improvement in their hyperhidrosis scores following treatment. The degree of improvement was less for the 1% glycopyrrolate group when compared with the Botulinum toxin type A group (P < 0.05), but there was no difference in treatment outcomes between the 2% glycopyrrolate and Botulinum toxin type A groups. No treatment group experienced reduced hyperhidrosis to a level similar to those without hyperhidrosis. Patients in both, the 2% glycopyrrolate and Botulinum toxin type A groups reported a significant improvement in axillary hyperhidrosis symptoms. These included reduction in psychologically precipitating factors (e.g. public speaking) and axillary hyperhidrosis-specific physical effects (e.g. limitation of clothing choice). CONCLUSIONS: Topical glycopyrrolate spray could provide a further treatment modality to manage axillary hyperhidrosis.

HLA-DQ allele-restricted activation of nitroso sulfamethoxazole-specific CD4-positive T lymphocytes from patients with cystic fibrosis.

BACKGROUND: For certain HLA allele-associated drug hypersensitivity reactions, the parent drug has been shown to associate directly with the risk allele. In other forms of hypersensitivity, HLA risk alleles have not been identified and T cells are activated in an allele unrestricted manner. Chemically reactive drug metabolites bind to multiple proteins; thus, it is assumed that the derived peptide antigens interact with a number of HLA molecules to activate T cells; however, HLA restriction of the drug metabolite-specific T-cell response has not been studied. OBJECTIVE: To utilize T cells from sulfamethoxazole (SMX) hypersensitive patients with cystic fibrosis to examine the HLA molecules that interact with nitroso SMX (SMX-NO)-derived antigens. METHODS: T-cell clones were generated from 4 hypersensitive patients. Drug-specific proliferative responses and cytokine secretion were measured. Anti-human class I and class II antibodies were used to analyse HLA restriction. Antigen-presenting cells expressing different HLA molecules were used to determine the alleles involved in the presentation of SMX-NO-derived antigens to T cells. RESULTS: A total of 976 clones were tested for SMX-NO reactivity. Thirty-nine CD4+ clones were activated with SMX-NO and found to proliferate and secrete cytokines. The SMX-NO-specific response was blocked with an antibody against HLA-DQ. SMX-NO-specific responses were detected with antigen-presenting cells expressing HLA-DQB1*05:01 (patient 1) and HLA-DQB1*02:01 (patient 2), but not other HLA-DQB1 alleles. CONCLUSION AND CLINICAL RELEVANCE: HLA-DQ plays an important role in the activation of SMX-NO-specific CD4+ T cells. Detection of HLA-DQ allele-restricted responses suggests that T cells are activated by a limited repertoire of SMX-NO-modified peptides.

Nitric oxide synthase in critically ischaemic muscle and alterations in isoform expression during revascularization surgery.

BACKGROUND: Dysfunction of the nitric oxide pathway is implicated in peripheral arterial disease. Nitric oxide synthase (NOS) isoforms and NOS activity were studied in muscle from patients with critical leg ischaemia (CLI). Alterations in NOS during revascularization surgery were also assessed. METHODS: Muscle biopsies were taken from patients with CLI undergoing amputation and also from patients undergoing femorodistal bypass at the start of surgery, after arterial clamping and following reperfusion. The presence of NOS within muscle sections was confirmed using reduced nicotinamide adenine dinucleotide phosphate diaphorase histochemistry. NOS isoform distribution was studied by immunohistochemistry. NOS mRNA and protein levels were measured using real-time reverse transcriptase-polymerase chain reaction and western blotting. NOS activity was assessed with the citrulline assay. RESULTS: All three NOS isoforms were found in muscle, associated with muscle fibres and microvessels. NOS I and III protein expression was increased in CLI (P = 0.041). During revascularization, further ischaemia and reperfusion led to a rise in NOS III protein levels (P = 0.008). NOS activity was unchanged. CONCLUSION: Alterations in NOS I and III occurred in muscle from patients with CLI and further changes occurred during bypass surgery.

A multicenter review of carotid body tumour management.

OBJECTIVE: Carotid body tumour (CBT) is a rare but the most common form of head and neck paraganglioma (PGL). We present the biggest ever series on CBT in UK/EU discussing diagnostic challenges, surgical treatment and complications of surgical intervention. METHOD: A detailed proforma was designed and sent to all members of Joint Vascular Research Group (JVRG). Data of 95 patients was collected. Generic terms including carotid body tumour/s, or paraganglioma/s were used to search a variety of electronic database in order to get latest informations available in literature. RESULTS: A total of 95 patients were recorded in our data from 1979 to 2005. Mean age of presentation was 55 years. Incidence was higher in females. CBT was more common on right side (58%). 18% tumours were bilateral. Neck lump (98%) and pressure symptoms including cranial nerve deficits and pain were main presenting complaints. About 18% of tumours were familial. Only 4.2% were malignant. Duplex scan is the best investigation for diagnosis, though MRI, DSA and CT scan are important for preoperative assessment. Surgery is the treatment of choice. Stroke and cranial nerve injury constitute postoperative morbidity (35%) and mortality (1%). Incidence of postoperative cranial nerve deficit was about 19%. Combined ipsilateral and contralateral recurrence rate was 4.2%. CONCLUSION: CBT is a rare condition which needs surgical excision by experienced vascular surgeon. Surgical resection is associated with significant morbidity of 35% and mortality of 1%. Mostly CBT is benign but malignant forms are not uncommon.

Alterations in purinoceptor expression in human long saphenous vein during varicose disease.

OBJECTIVES: Varicose veins are dilated tortuous veins of varying tone. Purinergic signalling is important in the control of tone and in mediating trophic changes in blood vessels. The expression of P2 receptors in control and varicose veins will be examined. METHODS: Purinergic signalling in circular and longitudinal smooth muscle of the human long saphenous vein was studied in control and varicose tissues using immunohistochemistry, organ bath pharmacology and electron microscopy. RESULTS: P2X1, P2Y1, P2Y2, P2Y4 and P2Y6 receptors were present on circular and longitudinal smooth muscle. Purine-mediated circular and longitudinal muscle contractions were weaker in varicose veins. Electron microscopy and immunohistochemistry findings support the view that smooth muscle cells change from the contractile to synthetic phenotype in varicose veins, associated with an upregulation of P2Y1 and P2Y2 receptors and a down regulation of P2X1 receptors. CONCLUSIONS: Down regulation of P2X1 receptors on the smooth muscle of varicose veins is associated with loss of contractile activity. Upregulation of P2Y1 and P2Y2 receptors is associated with a shift from contractile to synthetic and/or proliferative roles. The phenotype change in smooth muscle is associated with weakening of vein walls and may be a causal factor in the development of varicose veins.

Increased angiogenic response but deficient arteriolization and abnormal microvessel ultrastructure in critical leg ischaemia.

BACKGROUND: Ischaemia is known to induce angiogenesis, but the effects of critical leg ischaemia (CLI) on angiogenesis remain unclear. The aim of this study was to examine the physiological angiogenic response in CLI by investigating the extent of neovascularization, characterizing microvessel subtypes and determining the microvessel ultrastructure. METHODS: Gastrocnemius muscles were biopsied from 12 patients with CLI and 12 without leg ischaemia. Microvessels were evaluated immunohistochemically using three endothelial markers (anti-CD31, anti-CD34 and PAL-E) and anti-alpha smooth muscle actin (SMA) as a mural cell marker to label arterioles. Ki67 was used to demonstrate active cell proliferation. Further microvessel ultrastructural characteristics were determined by transmission electron microscopy. RESULTS: The CLI group had significantly higher microvessel density and microvessel : muscle fibre ratio for all endothelial subtypes examined (P < 0.001). PAL-E staining demonstrated the highest increase: 4.7 times higher in CLI muscle. There was no significant difference in alphaSMA-positive microvessel density (P = 0.118) or microvessel: muscle fibre ratio (P = 0.214). Ki67 staining showed no active cell proliferation. Transmission electron microscopy showed CLI microvessels had abnormal morphology, mainly a thick basement membrane. CONCLUSION: A physiological angiogenic response was found in CLI, but the microvessels had an abnormal ultrastructure. A lack of active cell proliferation suggests that the angiogenic response may have been exhausted.

Knee versus thigh length graduated compression stockings for prevention of deep venous thrombosis: a systematic review.

OBJECTIVE: Graduated compression stockings are a valuable means of thrombo-prophylaxis but it is unclear whether knee-length (KL) or thigh length (TL) stockings are more effective. The aim of this review was to systematically analyse randomised controlled trials that have evaluated stocking length and efficacy of thromboprophylaxis. METHOD: A systematic review of the literature was undertaken. Clinical trials on hospitalised populations and passengers on long haul flights were selected according to specific criteria and analysed to generate summated data. RESULTS: 14 randomized control trials were analysed. Thirty six of 1568 (2.3%) participants randomised to KL stockings developed a deep venous thrombosis, compared with 79 of 1696 (5%) in the TL control/thigh length group. Substantial heterogeneity was observed amongst trials. KL stockings had a significant effect to reduce the incidence of DVT in long haul flight passengers, odds ration 0.08 (95%CI 0.03-0.22). In hospitalised patients KL stockings did not appear to be far worse than TL stockings, odds ratio 1.01 (95%CI 0.35-2.90). For combined passengers and patients, there was a benefit in favour of KL stockings, weighted odds ratio 0.45 (95% CI 0.30-0.68). CONCLUSION: KL graduated stockings can be as effective as TL stockings for the prevention of DVT, whilst offering advantages in terms of patient compliance and cost.

Cryptic speciation in the cosmopolitan and clonal human pathogenic fungus Aspergillus fumigatus.

Microbes and other organisms smaller than one to a few millimeters in size are hypothesized to have global populations, in contrast to the geographically restricted ranges of larger organisms. However, fungi, which routinely have reproductive propagules no larger than 10 micrometers, challenge the generality of this hypothesis because recent studies have shown that globally distributed morphological species embrace two or more geographically restricted phylogenetic species. We used the concordance of gene genealogies to recognize phylogenetic species in the globally distributed opportunistic human pathogenic fungus, Aspergillus fumigatus. Based on DNA sequence data of five loci for each of 63 individuals collected from five continents, we have delineated two phylogenetic species in this single morphological species. Unlike all other fungi examined to date, both genetically isolated groups showed a global distribution with no evidence of a correlation between genotype and geographic location. Sexual reproduction has never been observed in A. fumigatus, but when the same data were used to explore the association of alleles at the five loci for one of the phylogenetic species, evidence was found to support recombination. The discovery of a cryptic species is medically relevant because different species are likely to differ in virulence or drug resistance. The discovery of a globally distributed A. fumigatus species clade highlights the need for ecological studies of the fungus to either document global dispersal or propose alternative mechanisms by which it persists as single, global phylogenetic population.

Time course of the GH/IGF axis response to fasting and increased ration in chinook salmon (Oncorhynchus tshawytscha).

Body growth in vertebrates is chiefly regulated by the GH/IGF axis. Pituitary growth hormone (GH) stimulates liver insulin-like growth factor-I (IGF-I) production. During fasting, plasma IGF-I levels decline due to the development of liver GH resistance, while GH levels generally increase. In mammals, decreased insulin during fasting is thought to cause liver GH resistance. However, the sequence of events in the GH/IGF axis response to fasting is not well characterized, especially in non-mammalian vertebrates. We assessed the time course of the GH/IGF axis response to fasting and increased ration in chinook salmon. Fish were placed on Fasting, Increased, or Control rations, and sampled daily for 4 days and at more widely spaced intervals through 29 days. Plasma IGF-I, GH, insulin, and 41 kDa IGF binding protein (putative salmon IGFBP-3), and liver IGF-I gene expression were measured. Control and Increased ration fish did not differ strongly. Plasma IGF-I and 41 kDa IGFBP were significantly lower in Fasted versus Control fish from day 4 onward, and liver IGF-I gene expression was significantly lower from day 6 onward. Liver IGF-I gene expression and plasma IGF-I levels were correlated. Plasma insulin was lower in Fasted fish from day 6 onward. There was a trend toward increased GH in Fasted fish on days 1-2, and GH was significantly increased Fasted fish from day 3 onward. Fasted GH first increased (days 1-3) to a plateau of 10-20 ng/ml (days 4-12) and then increased dramatically (days 15-29), suggesting that the GH response to fasting had three phases. The early increase in GH, followed by the decrease in plasma IGF-I after 4 days, suggests that GH resistance developed within 4 days.

Altered endothelin-1 levels in acute lower limb ischemia and reperfusion.

Tourniquet-induced ischemia is often used in orthopedic and reconstructive procedures. This is associated with muscle damage and dysfunction, which limits tourniquet application time. Endothelin-1 (ET-1) is a potent vasoconstrictor, which has been implicated in ischemic conditions and ischemia-reperfusion injury. This study aimed to investigate the role of ET-1 in human skeletal muscle subjected to tourniquet-induced acute ischemia and reperfusion. Thirteen patients undergoing total knee replacement were studied. Plasma and muscle ET-1 concentrations were measured at the start of surgery, after an hour of acute ischemia, and 15 minutes following reperfusion. ET-1 receptor binding was also studied by use of autoradiography, and ET-1 mRNA expression investigated by use of real-time polymerase chain reaction (RT-PCR). Tissue ET-1 increased following the period of acute ischemia and persisted during reperfusion. ET-1 was associated with microvessels and macrophages in the muscle. No changes in circulating ET-1 levels, ET-1 mRNA expression, or ET-1 receptor binding were found. It is concluded that the ET-1 pathway is involved in acute ischemia and reperfusion and it may contribute to the muscle injury that occurs during surgical procedures.

True juxta-anastomotic aneurysms in the residual infra-renal abdominal aorta.

INTRODUCTION: abdominal aortic dilatation can occur above the graft following repair of infra-renal abdominal aortic aneurysm (AAA). This study aimed to determine the incidence and possible aetiological associations of recurrent juxta-anastomotic aneurysms following open repair of AAA. METHODS: the diameter of the infra-renal aorta above the graft of 135 patients who had previously undergone open AAA repair was determined using ultrasound. In those where the diameter was greater than 40 mm a CT scan was undertaken. Co-morbid and operative details were determined from the patients and their clinical notes. RESULTS: seven patients had true juxta-anastomotic aneurysms (>40 mm) in the residual infra-renal abdominal aorta, the occurrence of which was associated with tobacco smoking and hypertension. There was no association with other co-morbid factors, surgical operative details or the development of iliac aneurysms (which occurred in 3% of patients). CONCLUSIONS: true juxta-anastomotic aneurysms develop in the residual infra-renal neck of patients following open repair of abdominal aortic aneurysm. Tobacco smoking and hypertension are significant factors associated with the development of these aneurysms. This group of patients may warrant surveillance to prevent aneurysm rupture.

Evidence for the involvement of endothelin-1 but not urotensin-II in chronic lower limb ischaemia in man.

BACKGROUND: endogenous vasoconstrictor peptides may play a role in the pathophysiology of critical limb ischaemia (CLI). This study investigated endothelin-1 (ET-1) and urotensin-II (U-II) mRNA expression, peptide distribution and ET receptor subtype binding in chronically ischaemic muscle. METHODS: open muscle biopsies were taken from patients undergoing amputations for CLI and from patients undergoing coronary artery bypass surgery (controls). ET-1 and U-II mRNA expression in muscle biopsies was studied using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). ET-1 and U-II immunohistochemistry was performed on muscle sections and ET receptor binding studied using in vitro autoradiography. RESULTS: ET-1 mRNA expression was significantly increased in CLI compared to controls (p<0.05) whilst no significant change in U-II expression occurred. ET-1 immunoreactivity was also increased in CLI with no difference in U-II immunostaining observed. ET(B) receptor binding was significantly increased in CLI (median 4, range 1-8 vs 2, range 1-3, dpm x 10(3)/mm(2), p=0.01, Mann-Whitney test) whilst ET(A) receptor binding was not significantly raised. Binding was associated with microvessels and macrophages. CONCLUSIONS: in CLI, the ET-1 pathway is upregulated but U-II is unaffected. ET-1 may vasoconstrict microvessels and mediate inflammation in chronically ischaemic muscle. ET-1 binding to ET(B) receptors in particular may play an important role in the pathophysiology of CLI underscoring the therapeutic potential of ET(B) receptor antagonists in the management of CLI.

Potential role of endothelin 1 in ischaemia-induced angiogenesis in critical leg ischaemia.

BACKGROUND: Ischaemia-induced angiogenesis occurs in critical leg ischaemia (CLI) and endothelin (ET) 1 may be involved in this process. The aim of this study was to quantify microvessels and study ET receptor expression and distribution in critically ischaemic leg muscle. METHODS: Leg muscle biopsies were taken from 12 patients with CLI and 12 patients with no leg ischaemia. Microvessels were identified immunohistochemically on muscle sections, and the number of immunopositive cells was quantified. ETA and ETB receptor messenger RNA (mRNA) expression was studied using real-time quantitative reverse transcriptase-polymerase chain reaction, and receptor binding was localized and assessed by in vitro autoradiography. RESULTS: The number of microvessels in CLI muscle biopsies was 2.6 times higher than that in controls (P < 0.01). ETB receptor mRNA expression and binding were significantly increased in CLI tissue (P < 0.05), while ETA receptor levels were not significantly raised. High-resolution autoradiography showed that ET receptor binding was associated with microvessels. CONCLUSION: Angiogenesis occurs in CLI and raised ETB receptors within the muscle were associated with microvessels, suggesting that ET-1 may mediate angiogenesis via these receptors in critically ischaemic muscle.