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Biomedical subjects

R Sutton

Publications and source records attributed to R Sutton.

At least 19 recordsLinked to original sources

Pacing for neurally mediated syncope: is placebo powerless?

BACKGROUND: After two recent controlled trials failed to prove superiority of cardiac pacing over placebo in patients affected by neurally mediated syncope, a widely accepted opinion is that cardiac pacing therapy is not very effective and that a strong placebo effect exists. AIM: To measure the effect of placebo pacing therapy. METHOD AND RESULTS: We compared the recurrence rate of syncope during placebo vs. no treatment in controlled trials of drug or pacing therapy. Syncope recurred in 38% of 252 patients randomized to placebo pooled from five trials vs. 34% of 881 patients randomized to no treatment pooled from eight trials. The corresponding recurrence rate with active cardiac pacing was 15% in 203 patients from six trials. CONCLUSIONS: Placebo is not an effective therapy for neurally mediated syncope. Different selection criteria in patients who are candidates for cardiac pacing-for example, presence, absence, or severity of the cardioinhibitory reflex may separate positive from negative trials.

Follow-Up Studies↗

Instantaneous effects of resynchronisation therapy on exercise performance in heart failure patients: the mechanistic role and predictive power of total isovolumic time.

BACKGROUND: Cardiac resynchronisation therapy improves peak oxygen uptake (peak VO(2)) 3-9 months after device implantation. In chronic heart failure, total isovolumic time (t-IVT) is a major determinant of peak VO(2) and of cardiac output at peak dobutamine stress. In selected patients, resynchronisation can instantaneously shorten t-IVT. We sought to determine the acute effect of resynchronisation on exercise performance and determine, with pharmacological stress echocardiography, the mechanism underlying this effect. METHODS AND RESULTS: Twenty-two patients with resynchronisation were studied within 3 months after device implantation. On a single study day, sequential cardiopulmonary exercise tests were performed during native activation (left bundle branch block) and resynchronisation (atrio-biventricular pacing) in random order. Total-IVT and cardiac output (at rest and peak dobutamine stress) were then measured in each activation mode. Resynchronisation acutely increased peak VO(2) by 1.6 (SD 1.5) ml/kg/min (p<0.001) and shortened peak stress t-IVT by 10 (SD 7) s/min (p<0.001), with the effects in individual patients showing a correlation (r = -0.46, p<0.05). Amongst all measurements during native activation, the best predictor of gain in peak VO(2) from resynchronisation was peak stress t-IVT (r = 0.71, p<0.001) with every increment of 5 s/min of peak stress t-IVT during native activation predicting an 8% gain in peak VO(2). No conventional measures during native activation at rest or on stress (including QRS duration, Tei index, tissue Doppler intraventricular delay, and resting t-IVT) added significant additional information. CONCLUSIONS: In eligible patients, resynchronisation can acutely augment peak VO(2), possibly through a mechanism of t-IVT shortening. Under native activation, long t-IVT during peak stress is the single best predictor of acute resynchronisation-mediated increment in peak VO(2).

Aged↗

Portosystemic shunts versus endoscopic therapy for variceal rebleeding in patients with cirrhosis.

BACKGROUND: Randomised clinical trials have compared portosystemic shunting procedures with endoscopic therapy for variceal haemorrhage, but there is no consensus as to which approach is preferable. OBJECTIVES: To compare the effects of shunts (total surgical shunt (TS); distal spleno-renal shunts (DSRS) or transjugular intrahepatic porto-systemic shunts (TIPS) with endoscopic therapy (ET, sclerotherapy and/or banding) for prevention of variceal rebleeding in patients with cirrhosis. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, MEDLINE, EMBASE, conference proceedings, and the references of identified trials were searched (last search February 2004). Researchers in the field and in industry were contacted. SELECTION CRITERIA: Randomised clinical trials comparing TS, DSRS or TIPS with ET in patients who had recovered from a variceal haemorrhage and were known to be cirrhotic. DATA COLLECTION AND ANALYSIS: Data were collected to allow intention-to-treat analysis where possible. For each outcome, a pooled estimate of treatment effect (log hazard ratio for time to outcome, Peto odds ratio for binary outcomes, and differences in means for continuous outcomes) across trials was calculated. MAIN RESULTS: Twenty-two trials evaluating 1409 patients were included. All trials had problems of method. Shunt therapy compared with ET demonstrated significantly less rebleeding (OR 0.24, 95% CI 0.18 to 0.30) at the cost of significantly increased acute hepatic encephalopathy (OR 2.07, 95% CI 1.59 to 2.69) and chronic encephalopathy (OR 2.09, 95% CI 1.20 to 3.62). There were no significant differences regarding mortality (hazard ratio 1.00, 95% CI 0.82 to 1.21) and duration of in-patient stay (weighed mean difference 0.78 day, 95% CI -1.48 to 3.05). The proportion of patients with shunt occlusion or dysfunction was 3.1% (95% CI 0.4 to 10.7%) following TS (two trials), 7.8% (95% CI 3.8 to 13.9%) following DSRS (four trials), and 59% (range 18% to 72%) following TIPS (14 trials). AUTHORS' CONCLUSIONS: All shunts resulted in a significantly lower rebleeding rate at the expense of a higher incidence of encephalopathy. TIPS was complicated by a high incidence of shunt dysfunction. No survival advantage was demonstrated with any shunt.

Endoscopy↗

Serum CA19-9 measurement increases the effectiveness of staging laparoscopy in patients with suspected pancreatic malignancy.

BACKGROUND/AIMS: Staging laparoscopy for suspected pancreatic neoplasia is not widely accepted due to its low yield. The aim of this study was to determine if serum carbohydrate antigen (CA19-9) levels could be used to improve the selection of patients for staging laparoscopy. METHODS: The data from a prospectively collected database (1997-2004) with 159 patients who had computed tomography-predicted resectable disease and who had undergone laparoscopic staging were analysed to determine if a low preoperative CA19-9 level (< or =150 kU/l, or < or =300 kU/l with a bilirubin >35 micromol/l) identified patients in whom laparoscopy was not useful. RESULTS: The CA19-9 level was >150 kU/l in 96 patients of whom 75 (78%) were considered resectable following laparoscopic assessment. There were 63 patients with a CA19-9 < or =150 kU/l of whom 60 (95%) were considered resectable following laparoscopic assessment. The sensitivity, specificity, positive predictive value and negative predictive value for CA19-9 < or =150 kU/l in predicting that laparoscopic assessment would judge patients as resectable were 44, 88, 95 and 22%, respectively. A cut-off level of < or =300 kU/l in patients with a bilirubin >35 micromol/l produced values of 30, 94, 94 and 28%, respectively. By using CA19-9 < or =150 kU/l, laparoscopy could have been avoided in 40% of patients, increased to 55% of patients with adjustment for the presence of jaundice; concomitantly, the yield from laparoscopy would have been increased from 15 to 22 and 25%, respectively. CONCLUSION: Use of serum CA19-9 levels would increase the efficiency of laparoscopic staging in patients with suspected pancreatic malignancy.

Bile Duct Neoplasms↗

Positron emission tomography does not add to computed tomography for the diagnosis and staging of pancreatic cancer.

BACKGROUND: Positron emission tomography (PET) has been proposed for pancreatic cancer diagnosis and staging. METHODS: 112 patients with suspected pancreatic cancer underwent 18F-fluoro-2-deoxy-D-glucose gamma camera PET and computed tomography (CT), of whom 62 also had laparoscopic ultrasonography and 70 underwent abdominal exploration for potential resection. The final diagnosis was malignancy in 78 and benign disease in 34 patients (25 with chronic pancreatitis). RESULTS: The diagnostic sensitivity and specificity for PET were 73 and 60% compared to 89 and 65% for CT respectively (Cohen's kappa = 0.59). In 30 patients CT was equivocal with cancer in 14 and benign disease in 16. PET correctly diagnosed 13 of these patients (cancer in 6 and benign disease in 7), interpreted 4 as equivocal (cancer in 3 and benign disease in 1) but was incorrect in the remaining 13 patients (cancer in 5 and benign disease in 8). The sensitivity and specificity for detecting small volume metastatic disease were 20 and 94% for CT and 22 and 91% for PET, respectively. CONCLUSION: PET had a similar accuracy to that of CT for imaging pancreatic cancer but it did not provide any additional information in patients with equivocal CT findings and currently would seem of little benefit for the staging of pancreatic cancer.

Adult↗

Comparison of Surgical Risk Score, POSSUM and p-POSSUM in higher-risk surgical patients.

BACKGROUND: Much current interest is focused on the use of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) and the Portsmouth predictor equation (p-POSSUM) for risk-adjusted surgical audit. The Surgical Risk Score (SRS) has been shown to offer an equivalent accuracy, but was validated using a cohort that contained a high proportion of low-risk patients. The aim of this study was to compare the accuracy of mortality prediction using SRS with that of POSSUM and p-POSSUM in a cohort of higher-risk patients. METHODS: Some 949 consecutive patients undergoing inpatient surgical procedures in a district general hospital under the care of a single surgeon were analysed. RESULTS: The observed 30-day mortality rate was 8.4 per cent. Mean mortality rates predicted using SRS, POSSUM and p-POSSUM scores were 5.9, 12.6 and 7.3 per cent respectively. No significant difference was observed in the area under the receiver-operator characteristic curves for the three methods. CONCLUSION: The SRS accurately predicted mortality in higher-risk surgical patients. The accuracy of prediction equalled that of POSSUM and p-POSSUM.

Hospital Mortality↗

Chemical signal mediated premating reproductive isolation in a marine polychaete, Neanthes acuminata (arenaceodentata).

Neanthes acuminata Ehlers (1868) is a monogamous coastal polychaete with male parental care and a high level of sexual selection. We measured the level of prezygotic isolation among allopatric populations of N. acuminata; from the East and West Coast of the USA, a population from Hawaii, and a laboratory culture originating from Los Angeles, CA. All populations were found to preferably mate with members of their own population. Individuals from populations from Atlantic vs. Pacific Ocean failed to pair and to mate, either during the 10 min or 48 hr experiments. Instead, individuals showed high levels of aggressive behavior. Experiments measuring the levels of interpopulation aggression, established that individuals can recognize and discriminate among different populations of N. acuminata on the basis of olfactory cues. Aggressive behavior was induced by exposure of animals to seawater "conditioned" by individuals from the other populations, thus demonstrating the role of olfaction in the detection of "home" populations. The aggressive display was stronger upon exposure to seawater conditioned with "unrelated" populations and especially between Pacific and Atlantic populations.

Aggression↗

Early and late complications after pancreatic necrosectomy.

BACKGROUND: Surgery for pancreatic necrosis is associated with a high morbidity and mortality. The aim of this study was to review the incidence of early and late complications after pancreatic necrosectomy in a large contemporary series of patients. METHODS: The clinical outcomes of 88 patients who underwent pancreatic necrosectomy between 1997 and 2003 were reviewed. RESULTS: The median age was 55.5 (range, 18-85) years, 54 (61%) were males, 68 (77%) had primary pancreatic infection, 71 (81%) had >50% necrosis, and the median admission Acute Physiology and Chronic Health Evaluation score was 9 (range, 1-21). Median time to surgery was 31 (range, 1-161) days; 47 patients underwent minimally invasive necrosectomy and 41 open necrosectomy; 81 (92%) of patients had complications postoperatively, and 25 (28%) died. Multiorgan failure (odds ratio = 3.4, P = .05) and hemorrhage (odds ratio = 6.1, P = .03) were the only independent predictors of mortality. During a median follow-up of 28.9 months, 39 (62%) of 63 surviving patients had one or more late complications: biliary stricture in 4 (6%), pseudocyst in 5 (8%), pancreatic fistula in 8 (13%), gastrointestinal fistula in 1 (2%), delayed collections in 3 (5%), and incisional hernia in 1 (2%); intervention was required in 10 (16%) patients. Sixteen (25%) of 63 surviving patients developed exocrine insufficiency, and 19 (33%) of 58 without prior diabetes mellitus developed endocrine insufficiency. CONCLUSIONS: Almost all patients undergoing necrosectomy developed significant early or late complications or both. Multiorgan failure and postoperative hemorrhage were independent predictors of mortality. Long-term follow-up was important because 62% developed complications, and 16% of those with complications required surgical or endoscopic intervention.

APACHE↗

Mechanisms of acinar cell injury in acute pancreatitis.

Acute pancreatitis has many causes, all leading to a common pathway of changes within the pancreatic acinar cell. Key amongst these changes is premature intracellular activation of digestive enzymes but this is also accompanied by the appearance of cytosolic vacuoles, co-localization of digestive and lysosomal enzymes, activation of NF-kappaB, and release of pro-inflammatory cytokines. The exact mechanism responsible for enzyme activation remains the subject of much research effort and not a little debate, however it is clear that all of these changes are triggered by an abnormal, sustained rise in cytosolic calcium concentration, which is itself dependent both on release of calcium from endoplasmic reticulum stores and uptake from the extracellular milieu. Activated enzymes are directly damaging to the acinar cell themselves, but recruitment of circulating neutrophils leads to further cellular damage. Cytokines and neutrophil activation are also responsible for the systemic inflammatory response typically seen in severe acute pancreatitis.

Acute Disease↗

Surgery in the treatment of acute pancreatitis--minimal access pancreatic necrosectomy.

Between 5% and 10% of patients with acute pancreatitis will develop infected pancreatic necrosis. Traditional open surgery for this condition carries a mortality rate of up to 50%, and therefore a number of less invasive techniques have been developed, including radiological drainage and a minimal access retroperitoneal approach. No randomised controlled trials have been published which compare these techniques. Indications for minimal access surgery are the same as for open surgery, i.e. infected pancreatic necrosis or failure to improve with extensive sterile necrosis. Access is obtained to the pancreatic necrosis via the left loin and necrosectomy performed using an operating nephroscope, and this often requires several procedures to remove all necrotic tissue. The cavity is continuously irrigated on the ward in between procedures. The results of this approach are encouraging, with less systemic upset to the patient, a lower incidence of post-operative organ failure when compared with open surgery, and a reduced requirement for ITU support. There is also a trend towards a lower mortality rate, although this does not reach statistical significance on the data published so far. Current evidence suggests that a minimal access approach to pancreatic necrosis is feasible, well tolerated and beneficial for the patient when compared with open surgery.

Dilatation↗

Comparative assessment of right, left, and biventricular pacing in patients with permanent atrial fibrillation.

AIMS: Left ventricular (LV) and biventricular (BiV) pacing are potentially superior to right ventricular (RV) apical pacing in patients undergoing atrioventricular (AV) junction ablation and pacing for permanent atrial fibrillation. METHODS AND RESULTS: Prospective randomized, single-blind, 3-month crossover comparison between RV and LV pacing (phase 1) and between RV and BiV pacing (phase 2) performed in 56 patients (70+/-8 years, 34 males) affected by severely symptomatic permanent atrial fibrillation, uncontrolled ventricular rate, or heart failure. Primary endpoints were quality of life and exercise capacity. Compared with RV pacing, the Minnesota Living with Heart Failure Questionnaire (LHFQ) score improved by 2 and 10% with LV and BiV pacing, respectively, the effort dyspnoea item of the Specific Symptom Scale (SSS) changed by 0 and 2%, the Karolinska score by 6 and 14% (P<0.05 for BiV), the New York Heart Association (NYHA) class by 5 and 11% (P<0.05 for BiV), the 6-min walked distance by 12 (+4%) and 4 m (+1%), and the ejection fraction by 5 and 5% (P<0.05 for both). BiV pacing but not LV pacing was slightly better than RV pacing in the subgroup of patients with preserved systolic function and absence of native left bundle branch block. Compared with pre-ablation measures, the Minnesota LHFQ score improved by 37, 39, and 49% during RV, LV, and BiV pacing, respectively, the effort dyspnoea item of the SSS by 25, 25, and 39%, the Karolinska score by 39, 42, and 54%, the NYHA class by 21, 25, and 30%, the 6-min walking distance by 35 (12%), 47 (16%), and 51 m (19%) and the ejection fraction by 5, 10, and 10% (all differences P<0.05). CONCLUSIONS: Rhythm regularization achieved with AV-junction ablation improved quality of life and exercise capacity with all modes of pacing. LV and BiV pacing provided modest or no additional favourable effect compared with RV pacing.

Aged↗

Fungal infection but not type of bacterial infection is associated with a high mortality in primary and secondary infected pancreatic necrosis.

INTRODUCTION: Knowledge of microbiology in the prognosis of patients with necrotizing pancreatitis is incomplete. AIM: This study compared outcomes based on primary and secondary infection after surgery for pancreatic necrosis. METHOD: From a limited prospective database of pancreatic necrosectomy, a retrospective case note review was performed (October 1996 to April 2003). RESULTS: 55 of 73 patients had infected pancreatic necrosis at the first necrosectomy. 25 of 47 patients had resistant bacteria to prophylactic antibiotics (n = 21) or did not receive prophylactic antibiotics (n = 4), but this was not associated with a higher mortality (9 of 25) compared to those with sensitive organisms (4 of 22). Patients with fungal infection (n = 6) had a higher initial median (95% CI) APACHE II score compared to those without (11 (9-13) verus 8.5 (7-10), p = 0.027). Five of six patients with fungal infection died compared to 13 of 47 who did not (p = 0.014). With the inclusion of secondary infections 21 (32%) of 66 patients had fungal infection with 10 (48%) deaths compared to 11 (24%) of 45 patients without fungal infection (p = 0.047). CONCLUSION: Whether associated with primary or secondary infected pancreatic necrosis, fungal but not bacterial infection was associated with a high mortality.

Bacterial Infections↗

Laparoscopy and laparoscopic ultrasound in the evaluation of pancreatic and periampullary tumours.

BACKGROUND AND AIMS: The pre-operative determination of resectability of pancreatic and peri-ampullary neoplasia assists the selection of patients for surgical or non-surgical treatment. This study investigated whether the addition of laparoscopy with laparoscopic ultrasound to dual-phase helical CT could improve the accuracy of assessment of resectability. PATIENTS AND METHODS: Prospective study of 305 patients referred to a single unit for consideration of pancreatic resection who underwent dual-phase helical CT scanning +/- laparoscopy with laparoscopic ultrasound. Data were collected on patient demographics, CT findings, assessment of operability, laparoscopic assessment (LA), surgical procedures and histology. RESULTS: LA was undertaken in 239/305 patients, 190 of whom were considered CT resectable, and 49 CT unresectable. Of the 190 CT resectable patients, LA correctly identified unresectability in 28 (15%: metastases in 15; vascular encasement in 6; anaesthesia for laparoscopy found 7 unfit for major resection) and incorrectly in 2 (vascular encasement), but did not identify unresectability in 33; LA correctly confirmed resectability in the remainder (prediction improved, chi(2) = 9.73, p < 0.01). Of the 49 CT unresectable patients, LA correctly identified resectability in 4, and incorrectly in 12, and correctly identified unresectability in the remaining 33. Sixty-six of the 305 patients did not undergo LA, of whom 23 underwent resection. CONCLUSION: When added to dual-phase helical CT, laparoscopy with laparoscopic ultrasound provides valuable information that significantly improves the selection of patients for surgical or non-surgical treatment.

Adult↗

Surgical treatment of pancreatic fistula.

BACKGROUND: Pancreatic fistula remains a significant problem in pancreatic disease, trauma and surgery. Whilst improved diagnostic and treatment techniques, including endoscopic approaches, have resulted in considerably improved outcomes, surgical intervention remains an important aspect of treatment but has been relatively poorly documented. AIMS: The aims were to review the recent world literature on the relative incidence of pancreatic fistula and the results of surgical treatment. RESULTS: The pancreatic fistula rate following partial pancreato-duodenectomy was 421 (12.9%) in 3,268 patients in 13 large series; 80 (13.0%) in 671 patients after left pancreatectomy in 6 large series, and 28 (11.9%) in 243 patients after pancreatic trauma in 4 recent series. The success rate of surgical procedures for external pancreatic fistulae was 101 (90.2%) in 112 patients with an overall mortality of 7 (6.3%) reported in 9 series. For internal pancreatic fistulae the success rate of surgical treatment was 61 (92%) in 66 patients with an overall mortality of 6 (9%) reported in 7 series. CONCLUSIONS: The treatment of established pancreatic fistula remains challenging. Although surgical treatment is reserved for patients who have failed all other treatments, the success rate is 90-92% but with a mortality of 6-9%.

Ascites↗

Diagnosis, treatment and outcome of pancreatoblastoma.

BACKGROUND: Pancreatoblastoma is a rare tumour mainly presenting in childhood but also in adults. OBJECTIVES: The aim was to determine the clinical course of pancreatoblastoma by an analysis of reported cases. METHODS: Patients with pancreatoblastoma were identified from Medline and combined with patients identified from the Royal Liverpool University Hospital. RESULTS: There were 153 patients with a median (range) age at presentation of 5 (0-68) years and a male:female ratio of 1.14:1. The most frequent site was the head of pancreas (48/123, 39%). The median and 5-year (95% CI) survival rates were 48 months and 50% (37-62%) respectively. At presentation there were 17 (17%) out of 101 patients with metastases, the liver being the commonest site (15/17, 88%). On univariate analysis, factors associated with a worse prognosis were synchronous (p = 0.05) or metachronous metastases (p < 0.001), non-resectable disease at presentation (p < 0.001) and age > 16 years at time of presentation (p = 0.02). On multivariate analysis, resection (p = 0.006) and metastases post-resection (p = 0.001) but not local recurrence influenced survival. CONCLUSIONS: Pancreatoblastoma is one of the pancreatic tumours with a relatively good prognosis. The treatment of choice is complete resection with long-term follow-up aiming to treat any early local recurrence or metastasis.

Child↗

Hereditary pancreatic endocrine tumours.

The two main types of hereditary pancreatic neuroendocrine tumours are found in multiple endocrine neoplasia type 1 (MEN-1) and von Hippel-Lindau disease (VHL), but also in the rarer disorders of neurofibromatosis type 1 and tuberous sclerosis. This review considers the major advances that have been made in genetic diagnosis, tumour localization, medical and surgical treatment and palliation with systemic chemotherapy and radionuclides. With the exception of the insulinoma syndrome, all of the various hormone excess syndromes of MEN-1 can be treated medically. The role of surgery however remains controversial ranging from no intervention (except enucleation for insulinoma), intervening for tumours diagnosed only by biochemical criteria, intervening in those tumours only detected radiologically (1-2 cm in diameter) or intervening only if the tumour diameter is > 3 cm in diameter. The extent of surgery is also controversial, although radical lymphadenectomy is generally recommended. Pancreatic tumours associated with VHL are usually non-functioning and tumours of at least 2 cm in diameter should be resected. Practice guidelines recommend that screening in patients with MEN-1 should commence at the age of 5 years for insulinoma and at the age of 20 years for other pancreatic neuroendocrine tumours and variously at 10-20 years of age for pancreatic tumours in patients with VHL. The evidence is increasing that the life span of patients may be significantly improved with surgical intervention, mandating the widespread use of tumour surveillance and multidisciplinary team management.

Endocrine Gland Neoplasms↗