In situ normothermic regional perfusion for controlled donation after circulatory death--the United Kingdom experience.

Organs recovered from donors after circulatory death (DCD) suffer warm ischemia before cold storage which may prejudice graft survival and result in a greater risk of complications after transplant. A period of normothermic regional perfusion (NRP) in the donor may reverse these effects and improve organ function. Twenty-one NRP retrievals from Maastricht category III DCD donors were performed at three UK centers. NRP was established postasystole via aortic and caval cannulation and maintained for 2 h. Blood gases and biochemistry were monitored to assess organ function. Sixty-three organs were recovered. Forty-nine patients were transplanted. The median time from asystole to NRP was 16 min (range 10-23 min). Thirty-two patients received a kidney transplant. The median cold ischemia time was 12 h 30 min (range 5 h 25 min-18 h 22 min). The median creatinine at 3 and 12 months was 107 µmol/L (range 72-222) and 121 µmol/L (range 63-157), respectively. Thirteen (40%) recipients had delayed graft function and four lost the grafts. Eleven patients received a liver transplant. The first week median peak ALT was 389 IU/L (range 58-3043). One patient had primary nonfunction. Two combined pancreas-kidney transplants, one islet transplant and three double lung transplants were performed with primary function. NRP in DCD donation facilitates organ recovery and may improve short-term outcomes.

Palliation of abdominal aortic aneurysms in the endovascular era.

OBJECTIVES: To establish outcome of patients with abdominal aortic aneurysm (AAA) deemed unfit for repair. DESIGN: Retrospective non-randomised study. MATERIALS AND METHODS: Identification of males with >5.5 cm or females with >5.0 cm AAA turned down for elective repair between 01/01/2006-24/07/2009 from a prospective database. Comorbidities, reasons for non-intervention, aneurysm size, survival, use of CPEX (cardio-pulmonary exercise) testing and cause of death were analysed. Although well-established at the time, patients unfit for open operation were not considered for endovascular repair. RESULTS: Seventy two patients were unsuitable for AAA repair. Aneurysm size ranged from 5.3 cm to 12 cm. Functional status, comorbidity and patient preference determined decision to palliate. Sixty percent of patients were alive at study close. Aneurysm rupture was cause of death in 46%. CPEX testing was performed in 54%, whose mortality was 28%, vs. 54% in the non-CPEX group (P < 0.05). Median survival of patients with 5.1-6.0 cm AAA was 44 months and 11% died of rupture. Between 6.1 and 7.0 cm median survival was 26 months and 20% died of rupture. However, with >7 cm aneurysms, survival was 6 months and 43% ruptured. CONCLUSION: Under half the deaths in our comorbid cohort were due to rupture. However, decision to palliate may be revisited as risk-benefit ratio changes with aneurysm expansion.

Validation and development of fluorescence two-dimensional differential gel electrophoresis proteomics technology.

Fluorescence two-dimensional differential gel electrophoresis (2-D DIGE*) is a new development in protein detection for two-dimensional gels. Using mouse liver homogenates (control and paracetamol (N-acetyl-p-aminophenol, APAP)-treated), we have determined the quantitative variation in the 2-D DIGE process and established statistically valid thresholds for assigning quantitative changes between samples. Thresholds were dependent on normalised spot volume, ranged from approximately 1.2 fold for large volume spots to 3.5 fold for small volume spots and were not markedly affected by the particular cyanine dye combination or by multiple operators carrying out the dye labelling reaction. To minimise the thresholds, substantial user editing was required when using ImageMaster 2D-Elite software. The difference thresholds were applied to the test system and quantitative protein differences were determined using replicate gels of pool samples and single gels from multiple individual animals (control vs treated in each gel). Throughout, the differences revealed with a particular cyanine dye combination were mirrored almost without exception when the dye combination was reversed. Both pool and individual sample analyses provided unique data to the study. The inter-animal response variability in inbred mice was approximately nine times that contributed by the 2-D DIGE process. A number of the most frequently observed protein changes resulting from APAP-treatment were identified by mass spectrometry. Several of these can be rationalised based on available data on the mechanism of APAP hepatotoxicity but others cannot, indicating that proteomics can provide further insights into the biochemical basis of APAP toxicity.

A prospective study examining the association between the symptoms of anxiety and depression and severity of urinary incontinence.

OBJECTIVE: To investigate the association of the presence or absence of the symptoms of anxiety and depression compared with the 48 h pad test as an objective measure of incontinence. DESIGN: Prospective study. SETTING: Urodynamics clinic in a large teaching hospital. SUBJECTS: All patients with urinary incontinence attending for urodynamic assessment from 23.4.96 to 29.10.96. INTERVENTIONS: 48 h pad test, Hospital Anxiety and Depression scale (HAD scale). MAIN OUTCOME MEASURES: Urodynamic diagnosis of cause of incontinence. Urinary loss over 48 h as measured by weight change in pads. Presence of symptoms of anxiety or depression as defined by HAD scale score of 8 or more. RESULTS: Urodynamic investigation was performed for incontinence on 133 patients. Of these 127 (95.4%) completed the HAD scale questionnaire. Of the 43 patients (32.2%) who returned the pads 18 (41.8%) patients were found to have symptoms of anxiety and six patients (13.9%) had symptoms of depression. Patients with symptoms of anxiety had lower mean measured urinary loss over a 48 h period compared to women with no symptoms of anxiety (median loss 44.2 ml range 6.8-622.4 versus 97.1 ml range 8.2-4384.4 ml) (P=0.05). There was no significant association between symptoms of depression and pad test results. CONCLUSIONS: Patients presenting with incontinence who have symptoms of anxiety are on average less incontinent compared to than those without symptoms of anxiety. It suggests that anxious patients present with a lesser degree of incontinence than nonanxious patients.

A prospective placebo controlled double blind randomised study to investigate the use of indoramin to prevent post-operative voiding disorders after surgical treatment for genuine stress incontinence.

A prospective placebo controlled double blind randomised study was undertaken to investigate the use of indoramin an alpha blocker to prevent post-operative voiding disorders after surgical treatment for genuine stress incontinence. Fifty-six patients were randomised to receive indoramin 20 mg orally twice a day or identical placebo from the first post-operative day until discharge from hospital. After seven exclusions, 49 patients were included in the study. There was no significant difference between the treatment (indoramin) group and placebo group for any of the outcomes measured. The routine use of indoramin to prevent post-operative voiding problems cannot be justified on the basis of these data.

Approximate standard errors in semiparametric models.

We consider semiparametric models with p regressor terms and q smooth terms. We obtain an explicit expression for the estimate of the regression coefficients given by the back-fitting algorithm. The calculation of the standard errors of these estimates based on this expression is a considerable computational exercise. We present an alternative, approximate method of calculation that is less demanding. With smoothing splines, the method is exact, while with loess, it gives good estimates of standard errors. We assess the adequacy of our approximation and of another approximation with the help of two examples.

Desmoid tumour of the thoracic outlet: an unusual cause of thoracic outlet syndrome.

Desmoid tumour is an unusual and aggressive tumour associated with a high recurrence rate. A 35-year-old man presented with recurrent debilitating left arm pain 2 years after undergoing bilateral transaxillary first rib resection for thoracic outlet syndrome. Nerve conduction studies demonstrated impairment of nerve conduction in the left arm. Magnetic resonance imaging of the brachial plexus demonstrated a mass at the apex of the left hemithorax involving the lower cord of the brachial plexus. Subsequent percutaneous needle biopsies failed to provided a definitive diagnosis. A cervicothoracic approach as described by Dartevelle was used to resect the lesion. Histologic and ultrastructural studies confirmed the diagnosis of a desmoid tumour. This report describes the atypical presentation of this unusual tumour and the application of the novel Dartevelle approach to secure its complete excision.

Clinical audit; who is auditing who?

Clinical audit is the principal means by which current clinical practice is improved. Doctors in training must gain positive experience of audit as juniors, so as to establish the importance of audit for future practice. Good audit requires involvement of doctors in training, a high level of participation and a leading role to be taken by the professional bodies. To examine the degree to which such criteria are met currently, the quality and prevalence of clinical audit, the participation of junior doctors in audit, and the preparedness of medical professional bodies' to guide audit were assessed. One hundred and twenty-six junior and senior house officers in three Edinburgh hospitals were administered questionnaires in person, whilst eight Royal Colleges, the British medical Association and the General Medical Council were assessed by the quality of their written guidelines for audit. The data showed that only thirteen out of twenty four specialties, which employed half the juniors, utilised clinical audit. Half of these audit programs were structured to lead to improved patient care. Surprisingly, only three out of ten professional bodies were able to provide good quality audit information. In conclusion, clinical audit is not universal practice and many existing audit programs are inappropriately structured. Commonly, doctors at all levels seemed unaware of the goals of clinical audit. In addition, the majority of professional bodies provide poor information, thereby impeding successful audit by doctors in training. Clinical audit will not succeed until such deficiencies are rectified.

The relationship between laparoscopic disease, pelvic pain and infertility; an unbiased assessment.

OBJECTIVES: To measure the relationship between laparoscopically detected pelvic pathology and pelvic pain or infertility. METHODS: Women undergoing diagnostic laparoscopy either for the investigation of pelvic pain, for sterilisation or for the investigation of infertility were studied. The indication for surgery was recorded before laparoscopy. At operation a series of 35-mm slide photographs were taken of the pelvis and later scored by two independent assessors without knowledge of the indication for surgery. RESULTS: Satisfactory photographs were obtained in 298 women. Minimal endometriosis was not associated with pain (adjusted OR 1.3; 0.5-2.8), although moderate disease was non-significantly so (2.5; 0.4-7.1). Severe disease was significantly more common and never occurred in patients being sterilised (P = 0.02). The odds of pain were not increased in the presence of dilated veins > 9 mm diameter (OR 1.1; 0.4-3.2) or adhesions (OR 0.6; 0.2-4.7). The odds of infertility were non-significantly increased in the presence of minimal and moderate endometriosis (OR 2.0; 0.8-5.3, and OR 4.2; 0.6-25 respectively) and again significantly more common in the presence of advanced disease (P = 0.002). The odds of infertility tended to be lower in the presence of severely dilated veins (OR 0.2; 0.032-1.2). There was no clear effect of adhesions (OR 0.9; 0.1-5.9). CONCLUSIONS: The long established associations between severe endometriosis and pelvic pain, and between endometriosis in general and infertility are confirmed. However there is little or no association between minimal endometriosis, pelvic adhesions or dilated pelvic veins and pain. Previously reported associations may have been an artefact of the surgeon's knowledge of the indication for operation when assessing the pelvis.

Vein quality influences neointimal hyperplasia in an organ culture model of human saphenous vein.

OBJECTIVES: The severity of pre-existing pathological changes in human saphenous vein (HSV) correlates with the development of vein graft stenosis and graft patency. The aim of this study was to investigate the influence of pre-existing intimal hyperplasia on development of the neointima in vitro, using an organ culture model. MATERIALS AND METHODS: Segments of HSV were harvested during coronary artery bypass surgery. Histology was performed on part of the vein; the remainder was maintained in culture. Pre-existing intimal thickness (PIT) in HSV from day 0 and neointimal thickness (NIT) in cultured HSV were measured using computerised image analysis on histological sections. Day 0 and 14 veins were compared with respect to intimal hyperplasia. RESULTS: Twelve pairs of veins were examined. A mean tissue ATP of 297 nmoles/g wet weight for cultured. HSV confirmed cell viability. Mean PIT was 180 microns (CI: 86-274) and mean NIT was 60 microns (CI: 48-72), with a significant correlation between them using the Spearman Rank test (Rs = 0.72; p = 0.008). CONCLUSIONS: Pre-existing vein quality as measured by PIT correlates with the development of neointimal hyperplasia in culture, adding further support to clinical evidence that poor vein quality predisposes to vein graft stenosis due to an inherent susceptibility to intimal hyperplasia.

Adipose tissue and lipid droplet embolism following periurethral injection of autologous fat: case report and review of the literature.

The authors present a case of a death associated with pulmonary adipose tissue and lipid droplet embolism following autologous fat harvesting, periurethral injection and videocystourethroscopy for the treatment of recurrent genuine stress incontinence.

Influence of angioscopic vein graft preparation on development of neointimal hyperplasia in an organ culture model of human saphenous vein.

PURPOSE: Angioscopy for in situ vein graft preparation has been criticized on the basis that the trauma of instrumentation may predispose to accelerated intimal hyperplasia, jeopardizing patency rates following infrainguinal revascularization. The aim of this study was to assess the effects of angioscopic preparation on endothelial integrity and smooth muscle cell (SMC) behavior in an established organ culture model of human saphenous vein (HSV). METHODS: HSV was harvested from 12 patients during bypass surgery before and after angioscopic preparation. Endothelial integrity was evaluated by immunohistochemical staining with JC-70 and scanning electron microscopy (SEM); remaining segments of pre- and postangioscopy vein were maintained in culture for 14 days in medium supplemented with 30% fetal calf serum. Viability was confirmed by measurement of tissue adenosine triphosphate on day 14 and thickness of the neointima was measured by computerized image analysis of histologic sections. Monoclonal antibodies to proliferating cell nuclear antigen (PCNA) were used as an immunohistochemical marker for proliferating SMCs. RESULTS: There was a significant reduction in the percentage staining by JC-70 (71.3% versus 20.4%) in pre- versus postangioscopy vein (p = 0.002 by Wilcoxon's rank test; n = 12). This was supported by SEM images. Despite this, there were no significant differences between the pre- and postangioscopy HSVs after 14 days of culture with respect to neointimal thickness (61 versus 56 microns) and staining with PCNA (4.80 versus 4.08 nuclei per 10 microns), all according to Wilcoxon's rank test. CONCLUSIONS: Angioscopic vein graft preparation is associated with endothelial cell loss but does not induce additional neointimal hyperplasia in HSV in vitro. These results suggest that angioscopic manipulation does not alter SMC behavior.

Hyperhomocysteinaemia is a risk factor for vein graft stenosis.

OBJECTIVES: Many infrainguinal vein graft failures are due to progressive vein graft stenosis (VGS) from intimal hyperplasia. Systemic factors have been implicated in the aetiology of intimal hyperplasia. Hyperhomocysteinaemia (HHCA) is established as an independent risk factor for coronary and peripheral arterial disease. The objective of this study was to examine the influence of HHCA and other serological factors upon the development of VGS. STUDY DESIGN: Thirty-eight patients who had undergone infrainguinal vein bypass were recruited to a case/control study from a graft surveillance program. Nineteen patients with documented VGS were matched against controls without stenosis for age, sex, length of time from surgery, diabetes, smoking history and preoperative symptom score. All patients were recalled for Duplex ultrasound scans, venesection and carbon monoxide estimation which were performed in a blinded fashion. RESULTS: Statistical analysis of all parameters revealed that plasma homocysteine was significantly elevated in patients with VGS (p < 0.3, Wilcoxon rank sum). CONCLUSIONS: These results suggest that HHCA is a previously unidentified risk factor for VGS. Patients with HHCA are susceptible to VGS and preoperative investigation would allow identification of patients at risk.

Homocysteine: an independent risk factor for the failure of vascular intervention.

Hyperhomocysteinaemia is an independent risk factor for the early development of arterial disease. Homocysteine and cardiovascular risk factors were assessed in 41 young and 25 older patients with vascular disease. As homocysteine may act by the generation of free radicals, total antioxidant capacity was measured. Hyperhomocysteinaemia was found in 29 per cent of patients but there was no difference between young and older patients. Homocysteine level was unrelated to other cardiovascular risk factors. Young age, diabetes and hyperhomocysteinaemia were independent risk factors for the failure of vascular procedures (P = 0.006). Patients with hyperhomocysteinaemia had raised total antioxidant capacity. The potential of identifying and treating a subgroup of patients with a poor prognosis deserves further study.

Angioscopically-assisted in situ saphenous vein bypass for infrainguinal revascularisation.

OBJECTIVES AND STUDY DESIGN: The diagnostic capability of angioscopy for endoluminal evaluation is established and its superiority over arteriography for completion studies has been confirmed. The therapeutic use of angioscopy in vein graft preparation is more controversial. The aim of this prospective study was to establish whether angioscopic vein preparation confers real benefits over existing techniques. METHODS: Forty-seven patients were randomised to either full angioscopic (ANG) vein preparation (23 patients) or conventional (CON) in situ grafting (19 patients). All patients underwent completion studies with arteriography and angioscopy and postoperatively, entered a Duplex graft surveillance programme. RESULTS: There was a significant difference in the incidence of wound morbidity: 26% in the ANG group as against 63% in the CON group (Fisher's exact test: p = 0.043), but no significant differences with respect to duration of operation, duration of vein graft preparation, length of hospital stay and both 30 day and 12 month secondary cumulative patencies (log rank test: p > 0.5). Completion angioscopy detected eight persistent valve cusps in six patients, all missed at arteriography, but failed to detect arteriovenous fistulae. CONCLUSIONS: Angioscopic preparation reduces wound morbidity and complements arteriography for detecting intraoperative defects. A large, prospective, randomised trial is now warranted to fully evaluate the potential therapeutic role of angioscopy with respect to current vascular practice.

Cutting the cost of emergency surgical admissions.

Over a one-month period, 207 general surgical emergency admissions (excluding urology) to a district general hospital were audited. The potential to improve the delivery of emergency care and reduce inpatient stay was studied. During the year of study, 44 per cent of all surgical admissions were emergency patients who consumed 61 per cent of inpatient bed days. Most emergency admissions were for gastroenterological problems although patients with arterial disorders tended to have relatively prolonged inpatient stays. Operations were performed in 34 per cent of emergency admissions with six post-operative deaths. Delays in operative treatment were mainly due to waiting for space on scheduled operating lists. A number of post-operative patients remained in hospital over the weekend awaiting discharge on Monday. Most emergency admissions were treated conservatively. Delays in discharge of fit patients occurred whilst the results of inpatient investigations were awaited. Twelve patients were admitted for complications of previous procedures. Emergency patients accounted for over half the inpatient bed days. There is considerable scope for improving the process of delivery of emergency surgical care and reducing inpatient stay.

Isolated tibial vessel disease: treatment options and outcome.

Tibial vessel disease is an important cause of limb ischaemia, particularly in diabetics. Revascularisation by angioplasty and bypass is increasingly feasible. The aim of this study was to review treatment and outcome in patients with this patterns of disease. We have performed 25 procedures in 20 patients since September, 1989. Six patients (5 diabetic) underwent 9 tibial angioplasties for stenotic lesions causing critical ischaemia or short-distance claudication. In 6 procedures there was single vessel run-off. Eight angioplasties were radiologically successful with a median increase in ankle-brachial index (ABI) of 0.15 [range: 0.00-0.44] at a median follow-up of 9 months. A further 4 patients (3 diabetic) with critical ischaemia underwent popliteal-distal, in-situ vein bypass for tibial occlusions. Distal anastomosis was onto the dorsalis pedis artery or distal anterior artery. Three grafts remain patent with successful limb salvage and ABI's greater than 1.0. Angioplasty is also useful for distal disease progression following femoro-popliteal bypass. Six patients with "at-risk" grafts underwent 8 tibial angioplasties for stenotic lesions in distal run-off. Radiologically, 6 procedures were successful with a median increase in ABI of 0.21 [range: 0.00-0.38] at a median follow-up of 7 months. There were less favourable results when a "graft-distal" bypass performed to salvage an occluded femoro-popliteal graft with diseased run-off vessels. Three of 4 grafts reoccluded within 3 months, 2 patients requiring amputation. We advocate an aggressive policy towards localised distal disease causing foot ischaemia.