Risk of stillbirth, preterm delivery, and fetal growth restriction following exposure in a previous birth: systematic review and meta-analysis.

BACKGROUND: Little is known about the risk of non-recurrent adverse birth outcomes. OBJECTIVES: To evaluate the risk of stillbirth, preterm birth (PTB), and small for gestational age (SGA) as a proxy for fetal growth restriction (FGR) following exposure to one or more of these factors in a previous birth. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Maternity and Infant Care, and Global Health from inception to 30 November 2016. SELECTION CRITERIA: Studies were included if they investigated the association between stillbirth, PTB, or SGA (as a proxy for FGR) in two subsequent births. DATA COLLECTION AND ANALYSIS: Meta-analysis and pooled association presented as odds ratios (ORs) and adjusted odds ratios (aORs). MAIN RESULTS: Of the 3399 studies identified, 17 met the inclusion criteria. A PTB or SGA (as a proxy for FGR) infant increased the risk of subsequent stillbirth ((pooled OR 1.70; 95% confidence interval, 95% CI, 1.34-2.16) and (pooled OR 1.98; 95% CI 1.70-2.31), respectively). A combination of exposures, such as a preterm SGA (as a proxy for FGR) birth, doubled the risk of subsequent stillbirth (pooled OR 4.47; 95% CI 2.58-7.76). The risk of stillbirth also varied with prematurity, increasing three-fold following PTB <34 weeks of gestation (pooled OR 2.98; 95% CI 2.05-4.34) and six-fold following preterm SGA (as a proxy for FGR) <34 weeks of gestation (pooled OR 6.00; 95% CI 3.43-10.49). A previous stillbirth increased the risk of PTB (pooled OR 2.82; 95% CI 2.31-3.45), and subsequent SGA (as a proxy for FGR) (pooled OR 1.39; 95% CI 1.10-1.76). CONCLUSION: The risk of stillbirth, PTB, or SGA (as a proxy for FGR) was moderately elevated in women who previously experienced a single exposure, but increased between two- and three-fold when two prior adverse outcomes were combined. Clinical guidelines should consider the inter-relationship of stillbirth, PTB, and SGA, and that each condition is an independent risk factor for the other conditions. TWEETABLE ABSTRACT: Risk of adverse birth outcomes in next pregnancy increases with the combined number of previous adverse events. PLAIN LANGUAGE SUMMARY: Why and how was the study carried out? Each year, around 2.6 million babies are stillborn, 15 million are born preterm (<37 weeks of gestation), and 32 million are born small for gestational age (less than tenth percentile for weight, smaller than usually expected for the relevant pregnancy stage). Being born preterm or small for gestational age can increase the chance of long-term health problems. The effect of having a stillbirth, preterm birth, or small-for-gestational-age infant in a previous pregnancy on future pregnancy health has not been summarised. We identified 3399 studies of outcomes of previous pregnancies, and 17 were summarised by our study. What were the main findings? The outcome of the previous pregnancy influenced the risk of poor outcomes in the next pregnancy. Babies born to mothers who had a previous preterm birth or small-for-gestational-age birth were more likely to be stillborn. The smaller and the more preterm the previous baby, the higher the risk of stillbirth in the following pregnancy. The risk of stillbirth in the following pregnancy was doubled if the previous baby was born both preterm and small for gestational age. Babies born to mothers who had a previous stillbirth were more likely to be preterm or small for gestational age. What are the limitations of the work? We included a small number of studies, as there are not enough studies in this area (adverse birth outcomes followed by adverse cross outcomes in the next pregnancy). We found very few studies that compared the risk of small for gestational age after preterm birth or stillbirth. Definitions of stillbirth, preterm birth categories, and small for gestational age differed across studies. We did not know the cause of stillbirth for most studies. What are the implications for patients? Women who have a history of poor pregnancy outcomes are at greater risk of poor outcomes in following pregnancies. Health providers should be aware of this risk when treating patients with a history of poor pregnancy outcomes.

Cytomegalovirus (CMV) infection and pregnancy-potential for improvements in Australasian maternity health providers' knowledge.

PURPOSE: To assess the knowledge, practice and attitudes of maternity clinicians regarding congenital cytomegalovirus (CMV). It is the most common congenital infection, and well-recognized cause of neurodevelopmental disability and hearing loss. New consensus recommendations state all pregnant women and health-care providers should be educated about congenital CMV infection and preventive measures. MATERIALS AND METHODS: An email questionnaire was distributed in October 2015 to specialists, diplomates (general practitioners), and trainees of the Royal Australian New Zealand College of Obstetricians and Gynaecologists (RANZCOG), and Victorian and New South Wales midwives. RESULTS: 774 responded: (37.3% specialists, 17.3% diplomates, 16.8% trainees, 28.6% midwives). Clinicians had variable knowledge of fetal sequelae, transmission routes and prevention. Overall, 30.2% felt confident about discussing CMV in pregnancy: less than 10% of midwives (7.4%) and less than half of specialists (47.1%, p < .0001). Only 8.8% of respondents routinely discussed CMV prevention with pregnant women. The majority (69.3%) responded that professional societies should make practice recommendations, and 88% thought more patient information was needed, preferably leaflets. CONCLUSIONS: Australasian maternity clinicians lack confidence and knowledge about congenital CMV. Few (<10%) routinely provide advice on prevention. There is urgent need for clinical guidance and patient information to reduce the burden of disease.

Inflammatory bowel disease in pregnancy: a population-based study of prevalence and pregnancy outcomes.

OBJECTIVE: To determine the prevalence of the inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), in pregnant women and determine pregnancy and fetal/neonatal outcomes. DESIGN: Population-based cohort study. SETTING: New South Wales, Australia, 2001-11. POPULATION: A total of 630 742 women who delivered at ≥20 weeks of gestation. METHODS: Descriptive and multivariate regression analyses of perinatal data linked to hospital admission data. We compared birth outcomes of women with and without a documented diagnosis of IBD. MAIN OUTCOME MEASURES: Caesarean section, severe maternal morbidity, preterm birth <37 weeks of gestation, planned preterm birth, small-for-gestational-age (birthweight <10th centile), perinatal mortality (stillbirth/neonatal death ≤28 days). RESULTS: In all, 1960 women (0.31%) with IBD, who had 2781 births (1183 UC, 1287 CD and 311 IBD-indeterminate). Women with IBD were more likely than women without IBD to have a caesarean section [41.5 versus 28.2%, adjusted risk ratio (aRR) 1.38, 95% CI 1.31-1.45], severe maternal morbidity (2.6 versus 1.6%, aRR 1.54, 95% CI 1.17-2.03), preterm birth (9.7 versus 6.6%, aRR 1.47, 95% CI 1.30-1.66), planned preterm birth (5.3 versus 2.9%, aRR 1.74, 95% CI 1.47-2.07), and their infants to be small-for-gestational-age (9.7 versus 9.5%, aRR 1.19, 95% CI 1.04-1.36). There was no evidence of a difference in perinatal mortality. CONCLUSION: Pregnancy-associated IBD is more common than previously reported. Pregnancies complicated by IBD at or near the time of birth have significantly higher rates of adverse pregnancy outcomes than pregnancies of women without IBD. TWEETABLE ABSTRACT: Increased rates preterm birth and caesarean section in women with inflammatory bowel disease.

Twin pregnancies complicated by gestational diabetes mellitus: a single centre cohort study.

AIMS: In women with a twin pregnancy, to determine the incidence of, risk factors for and outcomes of women with gestational diabetes mellitus, and assess how these have changed with a change in gestational diabetes screening. METHODS: Retrospective cohort study of women with a twin pregnancy attending an Australian tertiary hospital, 2002-2013. Information on gestational diabetes status, gestational diabetes risk factors and pregnancy outcomes was ascertained. Pregnancy outcomes included hypertensive disorders, twin birthweight centile and a composite adverse pregnancy outcome. Analysis was stratified pre/post screening protocol change (epoch 1: 2002-2009, epoch 2: 2010-2013) and by gestational diabetes status. RESULTS: Gestational diabetes was diagnosed in 86/982 (8.8%) women, increasing from 4.4% to 14.7% between epochs (P = 0.0001). The proportion of women with hypertensive disorders increased (11.7% vs. 13.4%, P = 0.009), but the proportion of infant's birthweight > 90th centile decreased (11.0% vs. 7.6%, P = 0.02) between epochs. Overall, 33.6% of women had ≥ 1 risk factors for gestational diabetes. Three-quarters (73.7%) of women overall had an adverse pregnancy outcome, with a slightly higher proportion in women with gestational diabetes compared with those with no gestational diabetes (79.7% vs. 73.1%, P = 0.06). The rate of the adverse pregnancy outcome did not change by epoch, after adjusting for maternal and pregnancy risk factors (adjusted odds ratio = 0.96, 95% confidence interval 0.73-1.26). CONCLUSIONS: Almost 1 in 10 women with a twin pregnancy were diagnosed with gestational diabetes, with the incidence of gestational diabetes increasing threefold with a new screening protocol. The pregnancy outcomes of women with a twin pregnancy did not change with increased detection and treatment for gestational diabetes.

A trial of mercaptopurine is a safe strategy in patients with inflammatory bowel disease intolerant to azathioprine: an observational study, systematic review and meta-analysis.

BACKGROUND: Thiopurines maintain remission and modify disease course in inflammatory bowel disease. Use is limited by intolerance and subsequent drug withdrawal in approximately 17% of patients treated with azathioprine. Previous case series have addressed the success rates of re-treatment with mercaptopurine in these individuals. AIMS: To determine the rate of tolerance when trialling mercaptopurine in azathioprine-intolerant patients and the factors predictive of success, and to perform a systematic review and meta-analysis of these data with other published data sets. METHODS: A retrospective observational study of 149 patients with IBD (82 with Crohn's disease and 67 with ulcerative colitis) previously intolerant of azathioprine subsequently treated with mercaptopurine was performed. A meta-analysis was undertaken of all published studies of mercaptopurine use in azathioprine-intolerant patients (455 patients in 11 included studies). RESULTS: Mercaptopurine was tolerated by 58% of azathioprine-intolerant patients in the Edinburgh cohort. In the meta-analysis, 68% tolerated mercaptopurine. A higher proportion of those in the meta-analysis with GI toxicity (62%) or hepatotoxicity (81%) were able to tolerate mercaptopurine than those with flu-like illness (36%). Among those patients who ceased mercaptopurine for further adverse effects, 59% experienced the same adverse effect as they had with azathioprine. CONCLUSIONS: This meta-analysis shows that switching to mercaptopurine is a safe therapeutic strategy for over two-thirds of azathioprine-intolerant patients and may help optimise immunomodulatory therapy in inflammatory bowel disease. A trial of mercaptopurine should be attempted in IBD patients (except those with acute pancreatitis or bone marrow aplasia) before considering thiopurine intolerance.

Occurrence and recurrence of diabetes in pregnancy.

AIMS: To determine occurrence and recurrence rates of gestational diabetes among women having at least two consecutive pregnancies. Risk factors for recurrence of gestational diabetes and rates of second/third pregnancy pre-existing diabetes mellitus were also assessed. METHODS: Population-based study using longitudinally linked hospital discharge and birth records (2001-2009) in NSW, Australia. Participants included women without a pre-existing diagnosis of Type 1 or Type 2 diabetes at time of first pregnancy and with at least a first and second birth. Factors associated with recurrence of gestational diabetes were examined using multivariate log-binomial models to adjust for correlation within mothers and estimate relative risks and 95% confidence intervals. RESULTS: First occurrence of gestational diabetes was 3.7% (5315/142 843) in the first pregnancy and 2.7% (3689/137 528) in the second pregnancy. The recurrence rate of gestational diabetes in a second consecutive pregnancy was 41.2%. Risk of pre-existing diabetes in a pregnancy subsequent to one with first occurrence of gestational diabetes was 2.2% and 2.0% in the second or third pregnancy, respectively. Among women with a diagnosis of gestational diabetes in the first pregnancy, independent predictors of gestational diabetes recurrence were maternal age ≥ 35 years, ethnicity (Middle East/North Africa and Asia), pregnancy hypertension, large for gestational age infant and preterm birth in the first pregnancy, longer inter-pregnancy birth interval and pregnancy hypertension and multiple pregnancy in the second pregnancy. CONCLUSIONS: Gestational diabetes in a previous pregnancy is a strong indicator of future risk and a useful clinical marker for identifying women at elevated risk in a subsequent pregnancy.

Clopidogrel, Turkey and a red herring?

The authors present the case of acute hepatitis E in a 61-year-old Edinburgh man who had returned from a holiday in Turkey 6 weeks previously. Diagnosis was ambiguous with his presentation initially attributed to a drug-induced liver injury.

Maternal vitamin D status in pregnancy and adverse pregnancy outcomes in a group at high risk for pre-eclampsia.

OBJECTIVE: To determine in a group of pregnant women if vitamin D status, based on serum 25-hydroxyvitamin D (25OHD) concentration, was associated with a subsequent risk of pre-eclampsia or adverse pregnancy outcomes. DESIGN: Prospective cohort study. SETTING: Vancouver, British Columbia, Canada (49°N). POPULATION: Women attending a specialist antenatal clinic because of clinical or biochemical risk factors for pre-eclampsia (n = 221). METHODS: Serum 25OHD concentration measured between 10 and 20 weeks of gestation. MAIN OUTCOME MEASURES: Pre-eclampsia and composite adverse pregnancy outcomes. RESULTS: Of the women, 78% were vitamin D insufficient (25OHD <75 nmol/l) and 53% were vitamin D deficient (25OHD <50 nmol/l). There was no difference in the rates of pre-eclampsia, gestational hypertension, preterm birth or composite adverse pregnancy outcomes by 25OHD concentration. CONCLUSIONS: Vitamin D deficiency and insufficiency were common in a group of women at high risk of pre-eclampsia; however, it was not associated with subsequent risk of an adverse pregnancy outcome.

Lack of association between cervical dysplasia and IBD: a large case-control study.

BACKGROUND: It has been variously reported that women with inflammatory bowel disease (IBD) have an increased risk of cervical dysplasia. We aimed to assess in a large, accurately phenotyped, case-controlled population whether women with IBD had increased rates of abnormal cervical smears and if this was affected by immunosuppressant therapy or disease phenotype. METHODS: Women with IBD diagnosed prior to the age of 60 were studied at a single tertiary referral center in Scotland. Full cervical smear histories were available on 411 women (204 Crohn's disease, 207 ulcerative colitis, median age at diagnosis 28.4 years, median current age 44.1 years). All the cases were matched 1:4 to healthy controls (n = 1644) from the same geographical location. RESULTS: There was no difference in rates of abnormal smears between patients with IBD (80.5% negative, 10.5% low-grade, and 9.0% high-grade dysplasia) and controls (85.4%, 7.7%, and 6.9%, P = 0.37). The use of immunosuppressant therapy had no impact on rates of cervical dysplasia or neoplasia. Furthermore, there was no effect of disease location, behavior, or oral contraceptive use. However, there were significantly more abnormal cervical smears in IBD patients who were current smokers compared with exsmokers and those who had never smoked (27.4% versus 11.4%, P = 0.001, odds ratio = 2.95, 95% confidence interval = 1.55-5.50). CONCLUSIONS: Women with IBD are not at increased risk of abnormal cervical smears unless they smoke. These data suggest that young women with IBD should be managed as per the background population; attending for regular smear testing, and undergoing vaccination against cervical cancer when available.

Fecal calprotectin predicts the clinical course of acute severe ulcerative colitis.

OBJECTIVES: Calprotectin is a granulocyte neutrophil-predominant cytosolic protein. Fecal concentrations are elevated in intestinal inflammation and may predict relapse in quiescent inflammatory bowel disease. We aim to investigate fecal calprotectin (FC) as a biomarker in predicting the clinical course of acute severe ulcerative colitis (ASUC). METHODS: In 90 patients with ASUC requiring intensive in-patient medical therapy (January 2005-September 2007), we investigated the discriminant ability of FC to predict colectomy and corticosteroid and infliximab nonresponse. All patients received parenteral corticosteroids as first-line treatment; 21 (23.3%) were also treated with infliximab (5 mg/kg), after failure of corticosteroid therapy. RESULTS: Of 90 patients, 31 (34.4%) required colectomy, including 11 (52.4%) of those treated with infliximab. Overall FC was high (1,020.0 microg/g interquartile range: 601.5-1,617.5). FC was significantly higher in patients requiring colectomy (1,200.0 vs. 887.0; P=0.04), with a trend toward significance when comparing corticosteroid nonresponders and responders (1,100.0 vs. 863.5; P=0.08), as well as between infliximab nonresponders and responders (1,795.0 vs. 920.5; P=0.06). Receiver-operator characteristic curve analysis yielded an area under the curve of 0.65 to predict colectomy (P=0.04), with a maximum likelihood ratio of 9.23, specificity 97.4%, and sensitivity 24.0% at a cutoff point of 1,922.5 microg/g. Kaplan-Meier analyses showed that using 1,922.5 microg/g over a median follow-up of 1.10 years, 87% of patients will need subsequent colectomy. CONCLUSIONS: This is the first data set to demonstrate that FC levels are dramatically elevated in severe UC. These data raise the possibility that this biomarker can predict response to first or second-line medical therapy in this setting.

Antenatal intravenous immunoglobulin in chronic immune thrombocytopenic purpura: case report and literature review.

Immune thrombocytopenic purpura (ITP) may complicate pregnancy and, uncommonly, may cause severe neonatal thrombocytopenia. However, it is difficult to predict which neonates are at risk of severe thrombocytopenia. Direct fetal sampling is not commonly done, as it poses significant risks to the fetus. Furthermore, appropriate antenatal treatment of neonates is controversial. We describe the case of a 32-year-old woman with chronic severe ITP and a previous severely affected infant, pregnant with trichorionic triplets, who was successfully managed with the use of weekly intravenous immunoglobulin 1 g/kg without recourse to direct fetal sampling.

Efficacy and complications of adalimumab treatment for medically-refractory Crohn's disease: analysis of nationwide experience in Scotland (2004-2008).

BACKGROUND: Adalimumab is a second generation humanized anti-tumour necrosis factor (TNF) monoclonal antibody with established efficacy in Crohn's disease (CD). AIMS: To evaluate the efficacy and safety of adalimumab on a nationwide clinical setting. METHODS: We used the Scottish Society of Gastroenterology network to identify and follow up the clinical outcomes of patients with CD treated with adalimumab over a 4-year period (2004-2008). RESULTS: A total of 98 patients received adalimumab - 100.5 patient follow-up years were recorded (64.3% females; median age at diagnosis of 20.7 years; 88.8% treated with 80/40 mg induction regimen. Eighty eight (89.8%) had previous infliximab with 29 (32.9%) primary nonresponders; 32 (32.6%) were corticosteroid-dependent; 47 (47.9%) were intolerant/resistant to most immunosuppressive therapies (two or more). In all, 60% of patients were in clinical remission at 1-year follow-up, with 30% and 55% requiring dose escalation to weekly therapy at 1-and 2-year follow-up respectively. Overall, 29 (29.6%) patients developed complications with eight nonfatal serious (8.2%) adverse events and 2 (2.0%) case fatalities (sepsis following perforation and disseminated colorectal cancer, respectively). CONCLUSIONS: Adalimumab is efficacious in severe and refractory CD in the clinical setting, although there remain significant therapy- and disease-related risks of serious complications.

The safety profile of anti-tumour necrosis factor therapy in inflammatory bowel disease in clinical practice: analysis of 620 patient-years follow-up.

BACKGROUND: Anti-TNF agents are now widely used in Crohn's disease (CD), and in ulcerative colitis (UC). AIM: To review the safety profile of anti-TNF agents in all patients treated with infliximab in Edinburgh from 1999 to 2007. METHODS: Complete data were available on 202/207 patients comprising 157 CD, 42 UC and three coeliac disease. Median follow-up was 2.4 years (1.0-4.9) with a total of 620 patient-years follow-up. About 19.1% of CD patients were subsequently treated with adalimumab. RESULTS: Seven deaths (3.3%) occurred in follow-up; only one death was <1 year post-infliximab (at day 72, from lung cancer). A total of six malignancies (three haematological, three bronchogenic) and six cases of suspected demyelination (three with confirmed neurological disease) were reported. In the 90 days following infliximab, 95 adverse events (36 serious) occurred in 58/202 (28.7%) patients. In all, 42/202 (20.8%) had an infectious event (22 serious) and 27/202 (13.4%) of patients had an infusion reaction: 19 acute (four serious) and eight delayed (three serious). CONCLUSIONS: Serious infections, malignancies and neurological disease complicate anti-TNF use in clinical practice. Although evidence for causality is unclear, potential mechanisms and predisposing factors need to be explored. In individual patients, the risk/benefit analysis needs to be carefully assessed and discussed prior to commencement of therapy.

Outcomes of pregnancies in women with pre-gestational diabetes mellitus and gestational diabetes mellitus; a population-based study in New South Wales, Australia, 1998-2002.

AIM: To determine population-based rates and outcomes of pre-gestational diabetes mellitus (pre-GDM) and gestational diabetes mellitus (GDM) in pregnancy. METHODS: This was a cross-sectional study, using linked population databases, of all women, and their infants, discharged from hospital following birth in New South Wales (NSW) between 1 July 1998 and 31 December 2002. Women with, and infants exposed to pre-GDM or GDM were compared with those without diabetes mellitus for pregnancy characteristics and outcomes. RESULTS: Women with a singleton pregnancy (n = 370,703) and their infants were included: 1248 women (0.3%) had pre-GDM and 17,128 (4.5%) had GDM. Of those women with pre-GDM, 57% had Type 1 diabetes, 20% had Type 2 diabetes and for 23% the type of diabetes was unknown. Major maternal morbidity or mortality was more common in women with pre-GDM (7.9%) [odds ratio (OR) 3.2, 95% confidence interval (CI) 2.6, 3.9] and in women with GDM (3.1%) (OR 1.2, 95% CI 1.1, 1.4) when compared with women without diabetes (2.6%). Major infant morbidity or mortality occurred more frequently in infants exposed to pre-GDM compared with no diabetes (13.6% vs. 3.1%) (OR 5.0, 95% CI 4.2, 5.8) and in infants exposed to GDM compared with no diabetes (3.2% vs. 2.3%) (OR 1.4, 95% CI 1.3, 1.5). CONCLUSIONS: Pre-GDM and GDM continue to be associated with an increased risk of adverse maternal and neonatal outcomes; however, women with GDM have adverse outcomes less frequently. Rates of GDM and pre-GDM appear to be increasing over time. Clinicians should consider the potential for adverse outcomes, and arrange referral to appropriate services.

The use of adalimumab in the management of refractory Crohn's disease.

BACKGROUND: Adalimumab is a humanized monoclonal antibody targeting tumour necrosis factor-alpha. Recent clinical trials have demonstrated its efficacy in Crohn's disease; however, experience in clinical practice remains limited. AIM: To investigate the efficacy and safety of adalimumab in the clinical setting. METHODS: The clinical outcomes of patients with medically refractory Crohn's disease treated with adalimumab in the Western General Hospital Edinburgh, over a 3-year period (2003-2006), were studied. RESULTS: Twenty-two (14 females; age at therapy: 32.6 years) patients were treated using an 80/40 mg induction regimen followed by fortnightly 40 mg treatment. All had proven refractory/intolerant to corticosteroids and immunosuppression. Twenty patients had had previous infliximab infusions - of these eight (36%), six (27%), three (14%) had previous infusion reactions, no response and lost response to infliximab, respectively. Over a period of 1.0 years (IQR: 0.62-2.5), Kaplan-Meier analyses showed that 68% (seven nonresponders) were in clinical remission and 67% (five surgery - discounting oral CD) avoided further surgery for active disease. 59% required dose escalation to 40 mg weekly (0.55 years; IQR: 0.22-1.4). Three (50%) primary nonresponders to infliximab achieved remission. Two patients developed serious infective complications and one patient developed lung cancer. CONCLUSIONS: Adalimumab is efficacious in refractory Crohn's disease, with benefit observed in infliximab primary nonresponders. However, many patients require escalation of dosing regimen.

A retrospective analysis of the efficacy and safety of infliximab as rescue therapy in acute severe ulcerative colitis.

BACKGROUND: Forty per cent of patients with acute severe ulcerative colitis will not respond to intravenous corticosteroids and require second-line medical therapy or colectomy. A recent controlled trial has suggested that infliximab may be effective as rescue therapy. AIM: To assess the value of infliximab as rescue therapy for acute severe colitis in a retrospective cohort of ulcerative colitis patients in Scotland. METHODS: All patients satisfied Truelove and Witts criteria on admission, failed to respond to intravenous corticosteroids and received infliximab (5 mg/kg) as rescue therapy. Response was defined as need for colectomy at hospital discharge and by 90 days. RESULTS: A total of 39 patients (median age 31.7 years) were treated. 26/39 (66%) responded, avoiding colectomy during the acute admission, and were followed up for a median of 203 days (Interquartile range = 135.5-328.5). Hypoalbuminaemia was a consistent predictor of non-response on univariate and multivariate analysis. At day 3 of intravenous steroids, 9/18 (50.0%) with serum albumin <34 g/L had urgent colectomy vs. 1/13 (7.7%) >or=34 g/L (P = 0.02, OR = 12.0, C.I. 1.28-112.7). Two serious adverse events occurred - one death due to Pseudomonas pneumonia, and one post-operative fungal septicaemia. CONCLUSIONS: Infliximab represents a moderately effective rescue therapy for patients with acute severe ulcerative colitis. Serious adverse events, including death, do occur and should be discussed with patients prior to therapy.

Dissemination of brain emboli following captive bolt stunning of sheep: capacity for entry into the systemic arterial circulation.

The epidemic of bovine spongiform encephalopathy in the United Kingdom and the recognition of a variant of Creutzfeldt-Jakob disease prompted revision of the guidelines for slaughter of cattle and sheep to prevent contamination of the edible parts of the carcass with central nervous system tissue. We previously showed that captive bolt gun stunning, which is routinely used for the slaughter of cattle and sheep, causes entry of fragments of central nervous system tissue into the jugular vein. To determine whether such tissue can traverse pulmonary capillaries to enter the systemic circulation, we introduced small volumes of brain tissue that had been disrupted by stunning with a captive bolt gun into the jugular vein of sheep sent for slaughter. We examined aortic blood samples by immunocytochemistry for neurofilament and S100 proteins and by enzyme-linked immunosorbent assay for glial fibrillary acidic protein and found fragments of neurofilament- and S100-immunopositive central nervous system tissue in samples from 2 of 11 sheep and elevated glial fibrillary acidic protein in 6 sheep. Our findings suggest that central nervous system tissue that is dislodged during routine captive bolt gun stunning and slaughter of sheep can enter the systemic arterial circulation and that, in some cases, this method of slaughter of an animal infected with bovine spongiform encephalopathy would be likely to contaminate edible parts of the carcass with infective material.

Erythromycin for the treatment of chronic intestinal pseudo-obstruction: description of six cases with a positive response.

BACKGROUND: Chronic intestinal pseudo-obstruction, due to intestinal myopathy or neuropathy, is characterized by the signs and symptoms of intestinal obstruction in the absence of true obstruction. Episodes are resistant to medical therapy. AIM: To determine the value of erythromycin treatment in chronic intestinal pseudo-obstruction. METHODS: All patients with proven chronic intestinal pseudo-obstruction treated with erythromycin were reviewed. Patients with symptomatic benefit are described in detail. Responders were compared with non-responders to identify the factors associated with benefit. RESULTS: Fifteen consecutive patients (nine females; median age, 37 years; median follow-up, 41 months) were treated with oral erythromycin, 1.5-2.0 g/day. Six patients (three primary visceral myopathy, two normal histology on light microscopy, one visceral myopathy secondary to scleroderma) responded, with decreased pain and vomiting, normalized bowel dysfunction and decreased episodes of ileus. Five of the six patients (83%) who responded to erythromycin were male, compared with two of the nine non-responders (22%) (P = 0.04). Four of the six responders (67%) had histological or immunohistological visceral myopathy, compared with three of the nine patients (33%) who failed to respond. Responders were less likely than non-responders to be taking long-term opiates. CONCLUSIONS: Erythromycin is effective for acute episodes of ileus and chronic symptoms in some patients with chronic intestinal pseudo-obstruction.