Altnagelvin Area Hospital

Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called "inflamm-aging." Despite research there is no clear understanding about the causes of "inflamm-aging" that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer's disease, rheumatoid arthritis, cancer, and aging itself. While inflammation is part of the normal repair response for healing, and essential in keeping us safe from bacterial and viral infections and noxious environmental agents, not all inflammation is good. When inflammation becomes prolonged and persists, it can become damaging and destructive. Several common molecular pathways have been identified that are associated with both aging and low-grade inflammation. The agerelated change in redox balance, the increase in age-related senescent cells, the senescence-associated secretory phenotype (SASP) and the decline in effective autophagy that can trigger the inflammasome, suggest that it may be possible to delay age-related diseases and aging itself by suppressing pro-inflammatory molecular mechanisms or improving the timely resolution of inflammation. Conversely there may be learning from molecular or genetic pathways from long-lived cohorts who exemplify good quality aging.

OBJECTIVE: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing's syndrome, because there is no recent consensus on the management of this rare disorder. PARTICIPANTS: Thirty-two leading endocrinologists, clinicians, and neurosurgeons with specific expertise in the management of ACTH-dependent Cushing's syndrome representing nine countries were chosen to address 1) criteria for cure and remission of this disorder, 2) surgical treatment of Cushing's disease, 3) therapeutic options in the event of persistent disease after transsphenoidal surgery, 4) medical therapy of Cushing's disease, and 5) management of ectopic ACTH syndrome, Nelson's syndrome, and special patient populations. EVIDENCE: Participants presented published scientific data, which formed the basis of the recommendations. Opinion shared by a majority of experts was used where strong evidence was lacking. CONSENSUS PROCESS: Participants met for 2 d, during which there were four chaired sessions of presentations, followed by general discussion where a consensus was reached. The consensus statement was prepared by a steering committee and was then reviewed by all authors, with suggestions incorporated if agreed upon by the majority. CONCLUSIONS: ACTH-dependent Cushing's syndrome is a heterogeneous disorder requiring a multidisciplinary and individualized approach to patient management. Generally, the treatment of choice for ACTH-dependent Cushing's syndrome is curative surgery with selective pituitary or ectopic corticotroph tumor resection. Second-line treatments include more radical surgery, radiation therapy (for Cushing's disease), medical therapy, and bilateral adrenalectomy. Because of the significant morbidity of Cushing's syndrome, early diagnosis and prompt therapy are warranted.

To investigate the contribution of glycation and oxidation reactions to the modification of insoluble collagen in aging and diabetes, Maillard reaction products were measured in skin collagen from 39 type 1 diabetic patients and 52 nondiabetic control subjects. Compounds studied included fructoselysine (FL), the initial glycation product, and the glycoxidation products, N epsilon-(carboxymethyl) lysine (CML) and pentosidine, formed during later Maillard reactions. Collagen-linked fluorescence was also studied. In nondiabetic subjects, glycation of collagen (FL content) increased only 33% between 20 and 85 yr of age. In contrast, CML, pentosidine and fluorescence increased five-fold, correlating strongly with age. In diabetic patients, collagen FL was increased threefold compared with nondiabetic subjects, correlating strongly with glycated hemoglobin but not with age. Collagen CML, pentosidine and fluorescence were increased up to twofold in diabetic compared with control patients: this could be explained by the increase in glycation alone, without invoking increased oxidative stress. There were strong correlations among CML, pentosidine and fluorescence in both groups, providing evidence for age-dependent chemical modification of collagen via the Maillard reaction, and acceleration of this process in diabetes. These results support the description of diabetes as a disease characterized by accelerated chemical aging of long-lived tissue proteins.

Glycation, oxidation, and browning of proteins have all been implicated in the development of diabetic complications. We measured the initial Amadori adduct, fructoselysine (FL); two Maillard products, N epsilon-(carboxymethyl) lysine (CML) and pentosidine; and fluorescence (excitation = 328 nm, emission = 378 nm) in skin collagen from 39 type 1 diabetic patients (aged 41.5 +/- 15.3 [17-73] yr; duration of diabetes 17.9 +/- 11.5 [0-46] yr, [mean +/- SD, range]). The measurements were related to the presence of background (n = 9) or proliferative (n = 16) retinopathy; early nephropathy (24-h albumin excretion rate [AER24] > or = 20 micrograms/min; n = 9); and limited joint mobility (LJM; n = 20). FL, CML, pentosidine, and fluorescence increased progressively across diabetic retinopathy (P < 0.05, P < 0.001, P < 0.05, P < 0.01, respectively). FL, CML, pentosidine, and fluorescence were also elevated in patients with early nephropathy (P < 0.05, P < 0.001, P < 0.01, P < 0.01, respectively). There was no association with LJM. Controlling for age, sex, and duration of diabetes using logistic regression, FL and CML were independently associated with retinopathy (FL odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.01-1.12, P < 0.05; CML OR = 6.77, 95% CI = 1.33-34.56, P < 0.05) and with early nephropathy (FL OR = 1.05, 95% CI = 1.01-1.10, P < 0.05; CML OR = 13.44, 95% CI = 2.00-93.30, P < 0.01). The associations between fluorescence and retinopathy and between pentosidine and nephropathy approached significance (P = 0.05). These data show that FL and Maillard products in skin correlate with functional abnormalities in other tissues and suggest that protein glycation and oxidation (glycoxidation) may be implicated in the development of diabetic retinopathy and early nephropathy.

BACKGROUND: Identification of lobar spontaneous intracerebral haemorrhage associated with cerebral amyloid angiopathy (CAA) is important because it is associated with a higher risk of recurrent intracerebral haemorrhage than arteriolosclerosis-associated intracerebral haemorrhage. We aimed to develop a prediction model for the identification of CAA-associated lobar intracerebral haemorrhage using CT features and genotype. METHODS: We identified adults with first-ever intracerebral haemorrhage diagnosed by CT, who died and underwent research autopsy as part of the Lothian IntraCerebral Haemorrhage, Pathology, Imaging and Neurological Outcome (LINCHPIN) study, a prospective, population-based, inception cohort. We determined APOE genotype and radiologists rated CT imaging appearances. Radiologists were not aware of clinical, genetic, and histopathological features. A neuropathologist rated brain tissue for small vessel diseases, including CAA, and was masked to clinical, radiographic, and genetic features. We used CT and APOE genotype data in a logistic regression model, which we internally validated using bootstrapping, to predict the risk of CAA-associated lobar intracerebral haemorrhage, derive diagnostic criteria, and estimate diagnostic accuracy. FINDINGS: Among 110 adults (median age 83 years [IQR 76-87], 49 [45%] men) included in the LINCHPIN study between June 1, 2010 and Feb 10, 2016, intracerebral haemorrhage was lobar in 62 (56%) participants, deep in 41 (37%), and infratentorial in seven (6%). Of the 62 participants with lobar intracerebral haemorrhage, 36 (58%) were associated with moderate or severe CAA compared with 26 (42%) that were associated with absent or mild CAA, and were independently associated with subarachnoid haemorrhage (32 [89%] of 36 vs 11 [42%] of 26; p=0·014), intracerebral haemorrhage with finger-like projections (14 [39%] of 36 vs 0; p=0·043), and APOE ɛ4 possession (18 [50%] of 36 vs 2 [8%] of 26; p=0·0020). A prediction model for CAA-associated lobar intracerebral haemorrhage using these three variables had excellent discrimination (c statistic 0·92, 95% CI 0·86-0·98), confirmed by internal validation. For the rule-out criteria, neither subarachnoid haemorrhage nor APOE ɛ4 possession had 100% sensitivity (95% CI 88-100). For the rule-in criteria, subarachnoid haemorrhage and either APOE ɛ4 possession or finger-like projections had 96% specificity (95% CI 78-100). INTERPRETATION: The CT and APOE genotype prediction model for CAA-associated lobar intracerebral haemorrhage shows excellent discrimination in this cohort, but requires external validation. The Edinburgh rule-in and rule-out diagnostic criteria might inform prognostic and therapeutic decisions that depend on identification of CAA-associated lobar intracerebral haemorrhage. FUNDING: UK Medical Research Council, The Stroke Association, and The Wellcome Trust.

Large-scale perturbation databases, such as Connectivity Map (CMap) or Library of Integrated Network-based Cellular Signatures (LINCS), provide enormous opportunities for computational pharmacogenomics and drug design. A reason for this is that in contrast to classical pharmacology focusing at one target at a time, the transcriptomics profiles provided by CMap and LINCS open the door for systems biology approaches on the pathway and network level. In this article, we provide a review of recent developments in computational pharmacogenomics with respect to CMap and LINCS and related applications.

Despite continuous progress in medicine, sepsis remains the main cause of deaths in the intensive care unit. Liver failure complicating sepsis/septic shock has a significant impact on mortality in this group of patients. The pathophysiology of sepsis-associated liver dysfunction is very complicated and still not well understood. According to the Surviving Sepsis Campaign (SSC) Guidelines, the diagnosis of liver dysfunction during sepsis is based on the increase in bilirubin concentration >2 mg/dL and the occurrence of coagulation disorders with INR > 1.5. The lack of specificity and ability to distinguish acute liver failure from previous liver dysfunction disqualifies bilirubin as a single parameter reflecting the complex liver function. Clinical manifestations of sepsis-associated liver dysfunction include hypoxic hepatitis, sepsis-induced cholestasis and dysfunction of protein synthesis manifesting with, e.g., coagulopathies. Detoxifying liver dysfunction, which is associated with an increase in serum ammonia concentration, manifesting with e.g., confusion, loss of consciousness and hepatic encephalopathy, may be disguised by analgosedation used in the intensive care unit. To determine a liver dysfunction in a critically ill patient, the concept of shock liver may be used. It is a complex syndrome of hemodynamic, cellular, molecular and immunologic changes leading to severe liver hypoxia. In clinical practice, there is no standardized diagnostic panel that would allow for an early, clear diagnosis of acute liver dysfunction, and there is no therapeutic panel enabling the full restoration of damaged liver function. The aim of the article is to present the pathophysiology and clinical manifestations of sepsis-associated liver dysfunction.

BACKGROUND: It is well established that a minority of celiac patients present with "classic" symptoms due to malabsorption. However, few studies have focussed on the distribution of body mass index (BMI) in celiac populations and its relationship to clinical characteristics, or on its response to treatment. METHODS: We reviewed BMI measurements and other clinical and pathological characteristics from a database of 371 celiac patients diagnosed over a 10-yr period and seen by a single gastroenterologist. To assess response to gluten exclusion, we compared BMI at diagnosis and after 2 yr treatment in patients with serological support for dietary compliance. RESULTS: Mean BMI was 24.6 kg/m2 (range 16.3-43.5). Seventeen patients (5%) were underweight (BMI < 18.5), 211 (57%) were normal, and 143 (39%) were overweight (BMI > or = 25), including 48 (13% of all patients) in the obese range (BMI > or = 30.0). There was a significant association between low BMI and female gender, history of diarrhea, reduced hemoglobin concentration, reduced bone mineral density (BMD), osteoporosis, and higher grades (subtotal/total) of villous atrophy. Of patients compliant with a gluten-free diet, 81% had gained weight after 2 yr, including 82% of initially overweight patients. CONCLUSIONS: Few celiac patients are underweight at diagnosis and a large minority is overweight; these are less likely to present with classical features of diarrhea and reduced hemoglobin. Failed or delayed diagnosis of celiac disease may reflect lack of awareness of this large subgroup. The increase in weight of already overweight patients after dietary gluten exclusion is a potential cause of morbidity, and the gluten-free diet as conventionally prescribed needs to be modified accordingly.

The accuracy of ultrasound imaging to identify lumbar intervertebral level was assessed in 50 patients undergoing X-ray of the lumbar spine. Using an ultraviolet marker, an anaesthetist attempted to mark the L2/3, L3/4 and L4/5 intervertebral spaces. A radiologist unaware of these marks attempted to mark the same spaces with the aid of ultrasound imaging. X-ray-visible pellets were taped to the back at the various marks prior to lateral lumbar X-ray. Ultrasound imaging identified the correct level in up to 71% of cases, but palpation was successful in only 30% (p < 0.001). Up to 27% of marks using the palpation method were more than one spinal level above or below the assumed level using palpation, but none were more than one level high or low using ultrasound guidance.

OBJECTIVES: To compare exposure to secondhand smoke and respiratory health in bar staff in the Republic of Ireland and Northern Ireland before and after the introduction of legislation for smoke-free workplaces in the Republic. DESIGN: Comparisons before and after the legislation in intervention and control regions. SETTING: Public houses in three areas in the Republic (intervention) and one area in Northern Ireland (control). PARTICIPANTS: 329 bar staff enrolled in baseline survey; 249 (76%) followed up one year later. Of these, 158 were non-smokers both at baseline and follow-up. MAIN OUTCOME MEASURES: Salivary cotinine concentration, self reported exposure to secondhand smoke, and respiratory and sensory irritation symptoms. RESULTS: In bar staff in the Republic who did not themselves smoke, salivary cotinine concentrations dropped by 80% after the smoke-free law (from median 29.0 nmol/l (95% confidence interval 18.2 to 43.2 nmol/l)) to 5.1 nmol/l (2.8 to 13.1 nmol/l) in contrast with a 20% decline in Northern Ireland over the same period (from median 25.3 nmol/l (10.4 to 59.2 nmol/l) to 20.4 nmol/l (13.2 to 33.8 nmol/l)). Changes in self reported exposure to secondhand smoke were consistent with the changes in cotinine concentrations. Reporting any respiratory symptom declined significantly in the Republic (down 16.7%, -26.1% to -7.3%) but not in Northern Ireland (0% difference, -32.7% to 32.7%). After adjustment for confounding, respiratory symptoms declined significantly more in the Republic than in Northern Ireland and the decline in cotinine concentration was twice as great. CONCLUSION: The smoke-free law in the Republic of Ireland protects non-smoking bar workers from exposure to secondhand smoke.

Given the increased reporting of multi-resistant bacteria and the shortage of newly approved medicines, researchers have been looking towards extreme and unusual environments as a new source of antibiotics. Streptomyces currently provides many of the world’s clinical antibiotics, so it comes as no surprise that these bacteria have recently been isolated from traditional medicine. Given the wide array of traditional medicines, it is hoped that these discoveries can provide the much sought after core structure diversity that will be required of a new generation of antibiotics. This review discusses the contribution of Streptomyces to antibiotics and the potential of newly discovered species in traditional medicine. We also explore how knowledge of traditional medicines can aid current initiatives in sourcing new and chemically diverse antibiotics.

OBJECTIVES: To characterize current practice in fluid administration and deresuscitation (removal of fluid using diuretics or renal replacement therapy), the relationship between fluid balance, deresuscitative measures, and outcomes and to identify risk factors for positive fluid balance in critical illness. DESIGN: Retrospective cohort study. SETTING: Ten ICUs in the United Kingdom and Canada. PATIENTS: Adults receiving invasive mechanical ventilation for a minimum of 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four-hundred patients were included. Positive cumulative fluid balance (fluid input greater than output) occurred in 87.3%: the largest contributions to fluid input were from medications and maintenance fluids rather than resuscitative IV fluids. In a multivariate logistic regression model, fluid balance on day 3 was an independent risk factor for 30-day mortality (odds ratio 1.26/L [95% CI, 1.07-1.46]), whereas negative fluid balance achieved in the context of deresuscitative measures was associated with lower mortality. Independent predictors of greater fluid balance included treatment in a Canadian site. CONCLUSIONS: Fluid balance is a practice-dependent and potentially modifiable risk factor for adverse outcomes in critical illness. Negative fluid balance achieved with deresuscitation on day 3 of ICU stay is associated with improved patient outcomes. Minimization of day 3 fluid balance by limiting maintenance fluid intake and drug diluents, and using deresuscitative measures, represents a potentially beneficial therapeutic strategy which merits investigation in randomized trials.

OBJECTIVE: To investigate video content on YouTube™ related to orthognathic surgery. MATERIALS AND METHODS: YouTube™ was searched using the terms: orthognathic surgery; orthodontic surgery; jaw surgery; jaw corrective surgery. Inclusion criteria included English language; primary content orthognathic surgery and acceptable audio-visual quality. Videos were sorted into the top 50 for each search term by view-count and into an overall top 60 from the four searches. The following parameters were recorded for each video: number of views; likes; dislikes; source; primary intention. Each was classified according to information content as 'excellent', 'moderate' or 'poor'. A pre-determined list of orthognathic surgery-related information domains was also evaluated. RESULTS: The top 60 videos had a combined total of 6,986,141 views. Videos predominantly involved patients describing their personal experience (41.67%) with the majority positively biased (61.67%). Only 9.17% of videos were classified as having excellent general information content and 55.83% were rated as poor. Surgical procedures were described in 45% whilst the need for pre- and post-surgical orthodontics was discussed in 33% and 16%, respectively. Post-operative paraesthesia was discussed in 17.5% of videos outcome. CONCLUSIONS: Video content on YouTube™ relating to orthognathic surgery is substandard and patients should be advised to view it with caution.

Campath-1H (alemtuzumab) is the most effective monoclonal antibody in single-agent use in B-cell chronic lymphocytic leukemia (CLL) with reported response rates of 33% to 70%. Combination therapy is now the conventional treatment for most hematologic malignancies. Monoclonal antibody treatments may sensitize tumor cells to subsequent chemotherapy. We report the combination of Campath-1H with fludarabine in patients with CLL refractory to each agent used singly. Six patients who had received a median of 8 courses of fludarabine (range, 4-10 courses) and 16 weeks of Campath-1H (range, 8-32 weeks) were treated. Five patients responded, including one who had a complete response by National Cancer Institute criteria. The responses observed were better in each patient than responses after each agent used singly. Complete morphologic bone marrow responses were seen in 3 patients, including eradication of disease measured by sensitive flow cytometry in 2. Campath-1H combined with fludarabine is a highly promising novel therapy for refractory CLL.

In a study of 247 patients who had general anaesthesia for dental procedures, the incidence of individual anxieties was noted using a questionnaire completed by the patient. The most common anxieties related to the period before transfer to the operating theatre, intra-operative awareness and postoperative pain. These anxieties were present in over half the patients questioned. The follow-up questionnaire was completed by 207 patients in order to indicate which anxieties they would expect to have if they needed anaesthesia in the future. All anxieties were less frequent than found before operation.

Mental health and behavioural problems are common among students commencing university. University life can be stressful and problems often exacerbate during their course of study, while others develop disorders for the first time. The WHO World Mental Health Surveys International College Student Project aims to conduct longitudinal research to examine and monitor student mental health and wellbeing. The Ulster University Student Wellbeing study, which commenced in September 2015 in Northern Ireland (NI), was conducted as part of this initiative (wave 1, n = 739), using the WMH-CIDI to examine psychopathology. Baseline prevalence rates of lifetime and 12-month mental health and substance disorders, ADHD and suicidality were high, with more than half of new undergraduate students reporting any lifetime disorder. Co-morbidity was common with 19.1% of students experiencing three or more disorders. Logistic regression models revealed that females, those over 21, non-heterosexual students, and those from a lower SES background were more likely to have a range of mental health and behavioural problems. Overall, 10% of new entry students received treatment for emotional problems in the previous year. However, 22.3% of students with problems said they would not seek help. The study provides important information for universities, policy makers and practice, on mental health and wellbeing in young people generally but particularly for students commencing university. The findings will assist in the development and implementation of protection and prevention strategies in the university setting and beyond.

AIMS: To profile site of stroke/cerebrovascular accident, type and extent of field loss, treatment options, and outcome. METHODS: Prospective multicentre cohort trial. Standardised referral and investigation protocol of visual parameters. RESULTS: 915 patients were recruited with a mean age of 69 years (SD 14). 479 patients (52%) had visual field loss. 51 patients (10%) had no visual symptoms. Almost half of symptomatic patients (n = 226) complained only of visual field loss: almost half (n = 226) also had reading difficulty, blurred vision, diplopia, and perceptual difficulties. 31% (n = 151) had visual field loss as their only visual impairment: 69% (n = 328) had low vision, eye movement deficits, or visual perceptual difficulties. Occipital and parietal lobe strokes most commonly caused visual field loss. Treatment options included visual search training, visual awareness, typoscopes, substitutive prisms, low vision aids, refraction, and occlusive patches. At followup 15 patients (7.5%) had full recovery, 78 (39%) had improvement, and 104 (52%) had no recovery. Two patients (1%) had further decline of visual field. Patients with visual field loss had lower quality of life scores than stroke patients without visual impairment. CONCLUSIONS: Stroke survivors with visual field loss require assessment to accurately define type and extent of loss, diagnose coexistent visual impairments, and offer targeted treatment.

Familial Hypercholesterolaemia is an autosomal, dominant genetic disorder that leads to elevated blood cholesterol and a dramatically increased risk of atherosclerosis. It is perceived as a rare condition. However it affects 1 in 250 of the population globally, making it an important public health concern. In communities with founder effects, higher disease prevalences are observed.We discuss the genetic basis of familial hypercholesterolaemia, examining the distribution of variants known to be associated with the condition across the exons of the genes LDLR, ApoB, PCSK9 and LDLRAP1. We also discuss screening programmes for familial hypercholesterolaemia and their cost-effectiveness. Diagnosis typically occurs using one of the Dutch Lipid Clinic Network (DCLN), Simon Broome Register (SBR) or Make Early Diagnosis to Prevent Early Death (MEDPED) criteria, each of which requires a different set of patient data. New cases can be identified by screening the family members of an index case that has been identified as a result of referral to a lipid clinic in a process called cascade screening. Alternatively, universal screening may be used whereby a population is systematically screened.It is currently significantly more cost effective to identify familial hypercholesterolaemia cases through cascade screening than universal screening. However, the cost of sequencing patient DNA has fallen dramatically in recent years and if the rate of progress continues, this may change.

OBJECTIVE: Although serum IgA-class endomysial antibody (EmA) has high sensitivity for villous atrophy (VA) in patients with untreated celiac disease, few studies have attempted to correlate EmA seroconversion with histological recovery after starting a gluten-free diet. We prospectively studied changes in EmA status and in duodenal histology of seropositive patients after dietary treatment. METHODS: Patients with VA and EmA had repeat EmA testing at 3, 6, and 12 months after starting gluten-free diet, plus assessment of dietary compliance by dietitians and follow-up duodenal biopsy at 12 months. VA before and after treatment was classified as partial (P), subtotal (ST), and total (T). RESULTS: Of 77 patients with newly diagnosed VA and without IgA deficiency, 62 (81%) had EmA: 46 of 57 (81%) with T or STVA and 16 of 20 (80%) with PVA. Of 53 initially EmA-positive patients who completed study criteria, EmA was undetectable in 31 patients (58%) after 3 months' diet, in 40 (75%) after 6 months, and in 46 (87%) after 12 months. However, only 21 patients (40%), all seronegative by 12 months, had complete villous recovery. Only three (33%) of 10 patients with persisting ST or TVA and two (9%) of 22 with PVA remained EmA positive. Four of the five patients with persisting EmA had poor dietary compliance. CONCLUSIONS: EmA is a poor predictor of persisting VA after patients have started gluten-free diet, although it may be of value in monitoring dietary compliance. Although there are no clear guidelines regarding the need for follow-up biopsy, EmA seroconversion cannot substitute. The apparent association between dietary compliance and seroconversion suggests that gluten intake may determine whether untreated celiac patients are EmA positive or negative for a given degree of small bowel damage.

BACKGROUND: Although IgA endomysial antibody (EmA) is currently the serologic test of choice in selecting suspected coeliac patients for duodenal biopsies, false-negative cases have been reported and may be more common than previous studies suggest. We assessed the sensitivity of EmA for patients with biopsy-confirmed villous atrophy (VA). METHODS: We studied 89 patients without IgA deficiency for whom biopsy had not been primarily prompted by a positive EmA result. VA was graded as partial, subtotal, or total (PVA, STVA, TVA). Serum EmA was assayed with indirect immunofluorescence. RESULTS: The sensitivity of EmA for VA was 78% (69 of 89) and was similar for PVA (79%) and ST/TVA (77%). Only 4 of the 20 EmA-negative patients had increased serum IgA-class antigliadin antibody levels as measured with enzyme-linked immunosorbent assay. All seronegative patients who complied with dietary gluten exclusion responded clinically, with histologic improvement after 12 months in 8 (67%) of 12 patients who had follow-up biopsies. CONCLUSIONS: EmA-negative coeliac disease is common. Reliance on EmA testing to select patients for biopsy will result in significant underdiagnosis.