Synthesis, structure and geometrically frustrated magnetism of the layered oxide-stannide compounds Fe(Fe3-xMnx)Si2Sn7O16.

Fe4Si2Sn7O16 has a unique crystal structure that contains alternating layers of Fe(2+) ions octahedrally coordinated by O (oxide layer) and Sn (stannide layer), bridged by SiO4 tetrahedra. The formula can be written as FeFe3Si2Sn7O16 to emphasise the distinction between the layers. Here, we report the changes in structure and properties as iron is selectively replaced by manganese in the oxide layer. Solid-state synthesis was used to produce polycrystalline samples of Fe(Fe3-xMnx)Si2Sn7O16 for x≤ 2.55, the structures of which were characterised using high-resolution synchrotron X-ray and neutron powder diffraction. Single-crystal samples were also grown at x = 0.35, 0.95, 2.60 and characterised by single crystal X-ray diffraction. We show that manganese is doped exclusively into the oxide layer, and that this layer contains exclusively magnetically active high-spin M(2+) transition metal cations; while the stannide layer only accommodates non-magnetic low-spin Fe(2+). All samples show clear evidence of geometrically frustrated magnetism, which we associate with the fact that the topology of the high-spin M(2+) ions in the oxide layer describes a perfect kagomé lattice. Despite this frustration, the x = 0 and x = 2.55 samples undergo long-range antiferromagnetic ordering transitions at 3.0 K and 2.5 K, respectively.

Direct and indirect effects of maltreatment typologies on suicidality in a representative Northern Irish sample: Psychopathology only partially mediates the relationship.

There has been a rise in suicide rates among men who grew up during the 1970's in Northern Ireland (NI). Conflict exposures (CEs) have been linked with suicide ideation but not attempts. Civil conflict has also been linked with aggressive parenting which is associated with the development of aggressive drives, psychopathology and suicidality. This study investigated (1) cohort specific associations between latent classes (LCs) of maltreatment and (2) associations between LCs, CEs, psychopathology and suicidality. Data were from NI Study of Health and Stress (N = 1986). Maltreatment and suicidality were queried using validated measures. Psychiatric assessments were based on DSM-IV criteria. Logistic regression, latent class analysis, chi square tests and mediation analyses were conducted. Two at risk LCs were identified, entitled "family violence exposure" (FVE, 10.4%; Male, 55.4%) and "family violence and sexual abuse exposure" (FVSAE, 1.2%; Female, 90.5%). Both were more likely to have experienced CEs (FVE = 71%; FVSAE = 77.5%) than the low risk class. The FVE were more likely to be male; aged 35-49 and to suffer from a mental disorder. The FVSAE class all endorsed rape, were more likely to be separated and to suffer from a mental disorder. CEs uniquely predicted ideation but not enactment. Psychopathology partially mediated the relationship between LCs and suicidality. FVE and FVSAE directly increased the odds of enactment. These findings are original and highly pertinent and they should be used to inform any strategy for addressing the cohort specific and trauma related rise in suicide rates in NI.

Cardiac ischaemia and rhythm disturbances during elective colonoscopy.

BACKGROUND: The number of colonoscopic procedures continues to rise rapidly. With widespread adoption of colonoscopy based bowel screening programmes, this rising trend is set to continue. AIMS: This study aimed to identify whether elective colonoscopy could provoke cardiac rhythm disturbances and/or myocardial ischaemia, as evidenced by 12 lead Holter ECG recordings and troponin I (cTnI) changes. MATERIALS AND METHODS: Patients were stratified into three groups based on the presence of cardiac disease or cardiovascular risk factors. They underwent real time 12 lead Holter monitoring before, during and after colonoscopy. Bloods were taken for pre- and post-procedure cTnI estimation. RESULTS: Holter ECG recordings of the three groups showed a high incidence of new but silent ischaemic and arrhythmic ECG changes during the colonoscopy in patients with documented but stable heart disease and to a lesser extent in those patients with one or more risk factors for heart disease. Three patients had high cTnI concentrations both before and after colonoscopy. Two patients with known heart disease died within 30 days of colonoscopy. CONCLUSIONS: This study demonstrates for the first time the occurrence of potentially clinically significant ST-T wave changes and rhythm disturbances during elective colonoscopy in patients with known heart disease and to a lesser extent in those patients with a known cardiovascular risk profile.

The value of auditing negative lower GI investigations preceding a final diagnosis of colorectal cancer.

OBJECTIVE: To review all preceding 'negative' large bowel investigations in patients with a final diagnosis of colorectal cancer, and to examine whether delayed diagnosis was associated with worse outcome. METHOD: Details were gathered on all patients with a new diagnosis of colorectal adenocarcinoma presenting over 4.5 years. For each patient the hospital's clinical workstation and radiology and endoscopy databases were interrogated for all flexible sigmoidoscopies, colonoscopies and barium enemas during the 5 years prior to diagnosis. RESULTS: Among the 570 patients, 28 (5%) had undergone colonoscopy and/or flexible sigmoidoscopy that had not shown colorectal cancer during the 5 years preceding final diagnosis, and a further 28 (5%) had undergone 'negative' barium enemas. Polyp surveillance might have missed four lesions destined to become malignant. Correspondingly there were three patients undergoing IBD surveillance found to have CRC, having had a negative complete colonoscopy within the preceding 5 years. Among patients undergoing de novo colonoscopy for diagnosis the true miss rate was only one patient per year. At August 2007, 29 (58%) of those with delayed diagnosis were still alive, compared with 216 (42%) of those diagnosed during initial investigation (chi2 = 5.04, P < 0.05). CONCLUSIONS: Colonoscopic miss rates are in line with previous studies. The application of simple clinical ground rules will avoid most pitfalls. The methodology described herein may assist in auditing the quality assurance of lower gastrointestinal diagnostic services. Despite the delay, late diagnosis was found to be associated with improved survival and a lower likelihood of metastatic disease.

Mode of delivery and risk of fecal incontinence in women with or without inflammatory bowel disease: questionnaire survey.

BACKGROUND: Elective cesarean section (CS) may be recommended for patients with Crohn's disease and perineal involvement. Little is known about CS rates in parous women with inflammatory bowel disease (IBD), nor the possible long-term impact of vaginal delivery and episiotomy on continence in women with IBD. METHODS: Questionnaires were sent to all 777 regional members of a Colitis and Crohn's Disease patient association. Male members were asked to request their unaffected female spouse/partner to complete the forms in order to give a "control" group for comparison. RESULTS: Forms were returned by 491 members (response rate 63%). CS had been undertaken for 37 of the 229 parous women with IBD (16%) versus 15 of the 116 without IBD (13%) (chi(2) = 0.62, P = NS). Only 2 women had undergone CS due to IBD. Of the parous women with IBD, 75 (33%) had persisting problems with fecal incontinence, of whom 21 (28%) dated this back to the time of vaginal delivery. By contrast, only 2 (2%) of the parous control group had suffered persisting fecal incontinence following vaginal delivery (chi(2) = 8.27, P < 0.01). CONCLUSIONS: Persisting fecal incontinence is reported by a significant minority of parous women with IBD, of whom over one-quarter date this back to vaginal delivery. CS is rarely recommended due to IBD alone. If our findings are confirmed in prospective studies, the threshold for recommending CS may need to be lowered for patients with IBD.

Proton pump inhibitor therapy is a risk factor for Clostridium difficile-associated diarrhoea.

BACKGROUND: Inhibition of gastric acid removes a defence against ingested bacteria and spores, increasing the risk of some forms of gastroenteritis. Previous studies investigating a possible link between acid suppression therapy and Clostridium difficile-associated diarrhoea have reported conflicting results. AIM: To investigate whether acid suppression therapy is associated with an increased risk of C. difficile-associated diarrhoea. Prospective case-control study of 155 consecutive in-patients with C. difficile-associated diarrhoea. RESULTS: Antibiotics had been received by 143 (92%) of the C. difficile-associated diarrhoea group and 76 (50%) of the controls during the preceding 3 months. Among those receiving antibiotics, 59 (41%) of the C. difficile-associated diarrhoea group had also received acid suppression, compared with 21 (28%) of controls (OR 1.84, CI 1.01, 3.36, chi(2) = 4.0, P = 0.046). Among the entire C. difficile-associated diarrhoea group 64 (41%) had received acid suppression compared with 40 (26%) of controls (OR 1.99, CI 1.19, 3.31, chi(2) = 7.9, P = 0.005). Logistic regression analyses found that C. difficile-associated diarrhoea was independently associated with: antibiotic use (OR 13.1, 95% CI: 6.6, 26.1); acid suppression therapy (OR 1.90, 95% CI: 1.10, 3.29); and female sex (OR 1.79, 95% CI: 1.06, 3.04). CONCLUSIONS: The risk of C. difficile-associated diarrhoea in hospitalized patients receiving antibiotics may be compounded by exposure to proton pump inhibitor therapy.

Colonoscopy first for iron-deficiency anaemia: a Numbers Needed to Investigate approach.

BACKGROUND: British Society of Gastroenterology guidelines recommend that gastrointestinal investigations should be considered in males and post-menopausal women presenting with iron-deficiency anaemia (IDA). AIM: To compare the diagnostic yields and clinical effectiveness of upper and lower gastrointestinal (GI) investigation in detecting malignancy among patients presenting with IDA. DESIGN: Retrospective review of case notes, endoscopy records and radiology reports. METHODS: We reviewed the results of 3798 investigations in 2600 patients presenting to our hospital with IDA from October 1995 to December 2003. The findings of the 2318 gastroscopies were compared with those of the 896 colonoscopies and the 584 barium enemas. Patients diagnosed with GI malignancy were identified and their outcomes determined. RESULTS: Gastroscopy identified 44 patients with newly-diagnosed upper GI cancer (18 oesophageal, 26 gastric). Thus for patients being gastroscoped for IDA, the Numbers Needed to Investigate (NNI) to detect each cancer was 53. Five-year survival for these 44 patients was 10%, so the NNI to identify each curable upper GI malignancy was 527. Colonoscopy or barium enema identified 111 (7.5%) patients with newly diagnosed colorectal cancer, giving a NNI of 13. Their 5-year survival was 35%, giving a NNI to identify each curable colorectal cancer patient of 38. DISCUSSION: Potentially curable gastrointestinal malignancy was diagnosed over 13 times more commonly using colonoscopy or barium enema vs. gastroscopy. For patients presenting with IDA, our findings favour investigating the lower GI tract first, or performing both gastroscopy and colonoscopy during the same endoscopy list.

Multidisciplinary team management is associated with improved outcomes after surgery for esophageal cancer.

We aim to compare the outcomes of patients undergoing R0 esophagectomy by a multidisciplinary team (MDT) with outcomes after surgery alone performed by surgeons working independently in a UK cancer unit. An historical control group of 77 consecutive patients diagnosed with esophageal cancer and undergoing surgery with curative intent by six general surgeons between 1991 and 1997 (54 R0 esophagectomies) were compared with a group of 67 consecutive patients managed by the MDT between 1998 and 2003 (53 R0 esophagectomies, 26 patients received multimodal therapy). The proportion of patients undergoing open and closed laparotomy and thoracotomy decreased from 21% and 5%, respectively, in control patients, to 13% and 0% in MDT patients (chi2 = 11.90, DF = 1, P = 0.001; chi2 = 5.45, DF = 1, P = 0.02 respectively). MDT patients had lower operative mortality (5.7%vs. 26%; chi2 = 8.22, DF = 1, P = 0.004) than control patients, and were more likely to survive 5 years (52%vs. 10%, chi2 = 15.05, P = 0.0001). In a multivariate analysis, MDT management (HR = 0.337, 95% CI = 0.201-0.564, P < 0.001), lymph node metastases (HR = 1.728, 95% CI = 1.070-2.792, P = 0.025), and American Society of Anesthesiologists grade (HR = 2.207, 95% CI = 1.412-3.450, P = 0.001) were independently associated with duration of survival. Multidisciplinary team management and surgical subspecialization improved outcomes after surgery significantly for patients diagnosed with esophageal cancer.

The prevalence of iron deficiency among patients presenting with colorectal cancer.

OBJECTIVES: To examine prospectively the prevalence of iron deficiency among new patients presenting with colorectal cancer and to compare transferrin saturation and serum ferritin as markers of iron deficiency in this group of patients. PATIENTS AND METHODS: Data were gathered on all patients presenting with a new diagnosis of colorectal cancer over a 12-month period. Iron status was estimated and, when possible, confirmed by measurement of serum ferritin concentration and transferrin saturation. Iron status was further examined in relation to tumour site and Dukes' stage. RESULTS: During the study 157 patients presented with a new colorectal cancer. Of these, 130 could be evaluated and 78[60%] had evidence of iron deficiency. Transferrin saturation was below the reference range in 55 patients, but serum ferritin was below in only 18 patients. Among the 49 patients with right-sided cancers, 39[80%] were iron deficient. Iron deficiency was significantly more likely in patients with right sided cancers compared with those with cancers at or distal to the splenic flexure (chi2 = 13, P < 0.001). CONCLUSION: The majority of patients with a new diagnosis of colorectal cancer are iron deficient at presentation. In such patients transferrin saturation measurement is a more sensitive marker of iron deficiency than serum ferritin. The potential role of measuring serum transferrin saturation as an adjunct to faecal occult blood screening should be explored further.

Prognostic significance of alarm symptoms in patients with gastric cancer.

BACKGROUND: The aim of this study was to determine the incidence and spectrum of alarm symptoms in patients with newly diagnosed gastric cancer, and to examine the relationship between symptoms and outcome. METHODS: Three hundred consecutive patients with gastric adenocarcinoma were studied prospectively. The outcomes of 40 patients (13.3 per cent) without alarm symptoms (21 men; median age 69 years) were compared with those of the 260 patients (86.7 per cent) with alarm symptoms (175 men; median age 72 years). RESULTS: It was possible to perform an R0 gastrectomy more often in patients without alarm symptoms (21 patients; 52 per cent) than in those with alarm symptoms (71 patients; 27.3 per cent) (chi(2) = 10.35, 1 d.f., P = 0.001). The cumulative survival rate at 5 years was 38 per cent for patients without alarm symptoms versus 15.0 per cent for those with alarm symptoms (chi(2) = 10.18, 1 d.f., P = 0.001). In a multivariate analysis, distant metastasis (hazard ratio (HR) 2.73 (95 per cent confidence interval (c.i.) 2.04 to 3.66); P < 0.001), overall stage of cancer (HR 1.83 (95 per cent c.i. 1.53 to 2.19); P < 0.001) and persistent vomiting at diagnosis (HR 1.66 (95 per cent c.i. 1.26 to 2.18); P < 0.001) were independently associated with length of survival. CONCLUSION: Alarm symptoms are absent in a significant minority of patients with gastric cancer at diagnosis; these patients stand a better chance of curative surgery and long-term survival than those with alarm symptoms.

GOAL: a simplified mental test for emergency medical admissions.

BACKGROUND: Several scoring systems are used in screening for cognitive impairment, but none are suited to the busy medical assessment environment. AIM: To construct, validate and assess the reliability of a simple scale (Gwent Orientation and Awareness Listing, GOAL) for this purpose, and to examine its application in consecutive emergency admissions in two general hospitals. DESIGN: Prospective cohort studies. METHODS: The validity and reliability of GOAL was assessed in three studies of patients aged > or =65 years who had been pronounced medically fit for discharge. The evaluation studies were carried out over 4-week medical intake periods in each participating hospital. RESULTS: Correlation of GOAL with the standard 30-point Mini-Mental State Examination was 0.89, and the inter-observer reliability was 0.90. Based on Receiver Operating Characteristics Curves, patients scoring <8 on GOAL were deemed to be cognitively impaired. Assessment by GOAL took half the time required for the widely used Abbreviated Mental Test Score. Of 1037 consecutive patients admitted to two hospitals' acute medical intakes and remaining for >24 h, 952 were able and willing to be scored by GOAL, and of these 201 (21%) 'failed', with a score of <8. DISCUSSION: Loss of orientation and awareness is common among patients admitted via medical intakes. GOAL is a practical brief screen for identifying and following-up these patients.

Prospective comparison of D1 vs modified D2 gastrectomy for carcinoma.

To compare the outcomes after D1 gastrectomy with those after modified D2 gastrectomy (preserving pancreas and spleen) performed by specialist surgeons for gastric cancer in a large UK NHS Trust. In all, 118 consecutive patients with gastric adenocarcinoma were referred by postcode, to undergo either a D1 gastrectomy (North Gwent (RJ), n=36, median age 76 years, 21 m) or a modified D2 gastrectomy (South Gwent (WL), n=82, 70 years, 57 m). Operative mortality in the two groups of patients was similar (D1 8.3% vs D2 7.3%, chi2 0.286, DF 1, P=0.593). Overall cumulative survival at 5 years was 32% after D1 gastrectomy compared to 59% after D2 gastrectomy (chi2 4.25, DF 1, P=0.0392). In patients with stage III cancers, survival was 8% after D1, compared with 33% after D2 gastrectomy (chi2 6.43, DF 1, P=0.0112). In a multivariate analysis, T stage (hazard ratio 2.339, 95% CI 1.683-2.995, P=0.01), N stage (hazard ratio 4.026, 95% CI 3.536-4.516, P=0.0001) and the extent of lymphadenectomy (hazard ratio 0.258, 95% CI -0.426-0.942, P=0.0001) were independently associated with durations of survival. In conclusion, modified D2 gastrectomy can improve survival four-fold for patients with stage III gastric cancer, without significantly increasing morbidity and mortality when compared with a D1 gastrectomy.

Comparison of special interest computed tomography, endosonography and histopathological stage of oesophageal cancer.

AIMS: To assess the strength of agreement between the perceived pre-operative stage of oesophageal tumours as determined by spiral computed tomography (CT) and endoscopic ultrasound (EUS), both alone and in combination, with the histopathological stage. METHODS: Sixty patients with oesophageal cancer underwent both pre-operative CT and EUS performed by two consultant radiologists with a special interest in upper gastrointestinal radiology. The strength of the agreement between the radiological stage and the histopathological stage was determined by means of the weighted Kappa statistic (Kw). RESULTS: Sensitivity for T and N stages was 58% and 79% for CT, and 72% and 91% for EUS. Specificity for T and N stages was 80% and 84% for CT, and 85% and 68% for EUS. Kw for T and N stages was 0.455 (p=0.0001) and 0.603 (p=0.0001) for CT compared with 0.604 (p=0.0001) and 0.610 (p=0.0001) for EUS. In patients when CT and EUS agreed regarding the T and N stages, the strength of agreement between the radiological and the histopathological stage was greater (Kw T 0.613 (p=0.0001), Kw N 0.781 (p=0.0001)). CONCLUSION: CT and EUS are complimentary techniques for the staging of oesophageal tumours, and these results reinforce the importance of specialist radiology in stage directed management.

A comparison of three types of biopsy forceps in the endoscopic surveillance of Barrett's oesophagus.

BACKGROUND AND STUDY AIMS: Periodic endoscopic biopsy surveillance is recommended for selected patients with Barrett's oesophagus. A new angled swing-jaw forceps has become available which is said to facilitate tangential oesophageal biopsy sampling. We examined the size and quality of oesophageal biopsies obtained with the forceps of angled design in comparison with the large cup disposable forceps and the conventional reusable upper gastrointestinal forceps. PATIENTS AND METHODS: In this prospective comparative study, three biopsies were taken at each of three levels, using a different design of forceps at each level, in each of 48 patients undergoing endoscopic surveillance. The order in which the forceps were used was randomized. A pathologist assessed the size and quality of each set of biopsies obtained. RESULTS: The mean biopsy diameter was significantly greater at 3.00 mm with the angled forceps (P < 0.01), in comparison with 2.52 mm with the elliptical forceps and 2.07 mm with the conventional forceps. Fewer biopsies obtained with the angled forceps were graded as inadequate (8.3 %) compared with those obtained using the disposable large cup and conventional forceps (25 % and 22.9 %, respectively). CONCLUSIONS: The design of forceps used influences the size and quality of tissue obtained during endoscopic surveillance of Barrett's oesophagus. The angled swing-jaw forceps are recommended as the most suitable for this purpose.

A randomized placebo-controlled trial of a humanized monoclonal antibody to alpha4 integrin in active Crohn's disease.

BACKGROUND & AIMS: alpha4 integrins are important mediators of leukocyte migration across vascular endothelium. This pilot placebo-controlled study aimed to assess the safety and efficacy of natalizumab, a recombinant humanized monoclonal antibody to alpha4 integrin, in patients with mild to moderately active Crohn's disease. METHODS: Thirty patients with active Crohn's disease (Crohn's Disease Activity Index [CDAI] > or =151 and < or =450) received a 3-mg/kg infusion of natalizumab (n = 18) or placebo (n = 12) by double-blind randomization. The study's primary endpoint was change in CDAI at week 2. RESULTS: At week 2, the CDAI decreased significantly from baseline after infusion of natalizumab (mean 45 points) but not placebo (mean 11 points). Seven (39%) natalizumab-treated patients achieved remission at week 2, compared with 1 (8%) treated with placebo. In contrast, 4 (33%) of the placebo-treated patients required rescue medication by week 2, compared with 2 (11%) natalizumab-treated patients. Significant increases in circulating B and T lymphocytes were detected only after natalizumab administration. The frequency of commonly reported adverse events did not differ significantly between groups. CONCLUSIONS: A single 3-mg/kg natalizumab infusion was well tolerated by Crohn's disease patients, although the dose used may have been suboptimal. Elevated circulating lymphocyte levels after natalizumab suggest interrupted lymphocyte trafficking. Natalizumab therapy in active Crohn's disease merits further investigation.

Provision of ERCP services and training in the United Kingdom.

BACKGROUND AND STUDY AIMS: A rising demand for hands-on training in endoscopic retrograde cholangiopancreatography (ERCP) has coincided with a need for increased scrutiny of outcomes (clinical governance) and the development of less invasive methods of pancreaticobiliary imaging. We surveyed the current provision of ERCP facilities and training throughout the United Kingdom. METHODS: Questionnaires were sent to senior endoscopists in 252 acute hospitals and to 500 trainees in gastroenterology. RESULTS: Completed forms were returned from 180 hospitals (a 71% response rate) and from 233 trainees (a 47% response rate). A median of 210 ERCPs per year are carried out at each centre (range 40-1000), under the supervision of 345 senior endoscopists. ERCP training had been started by 163 trainees (70%), of whom 42 (26%) had been given one or fewer procedures to start per week. Trainees rated their training as excellent (25%), good (28%), adequate (24%) or inadequate (22%); 193 (83%) perceived that they needed training in ERCP to ensure that future career opportunities were not denied to them. CONCLUSIONS: Some centres have insufficient capacity for training in ERCP. Some form of preselection for both trainers and trainees may be required to ensure that quality is maintained. Gastroenterology training programmes should move away from encouraging all trainees to learn ERCP, and should promote the acquisition of alternative skills.

Buckling of redundant expansile stent distal to an oesophageal cancer: endoscopic management.

This report describes a complication that occurred as a result of deploying an Ultraflex stent too low in relation to a stenosing carcinoma of the gastro-oesophageal junction. Intermittent kinking of the redundant lower end of the stent caused frequent episodes of total dysphagia. A percutaneous endoscopic gastrostomy was deployed to anchor the redundant portion of the stent within the stomach, allowing it to be shortened with endoscopic stitch cutters. This procedure relieved the episodic dysphagia, and was well tolerated.