Psychosocial health and quality of life in ICSI and naturally conceived adolescents: a cross-sectional comparison.

PURPOSE: Psychosocial health (PH) and quality of life (QoL) are important health outcomes. We compared PH and QoL of adolescents conceived with intrazytoplasmatic sperm injection (ICSI) and of naturally conceived controls. The impact of disclosure of ICSI-conception on QoL and PH was quantified. METHODS: The cross-sectional sample consisted of 545 ICSI-conceived adolescents and 427 unmatched singleton controls aged 14-18 years. Adolescents reported PH with the 'Strengths and Difficulties Questionnaire' (low values indicating high PH), and QoL with the KINDL questionnaire (high values indicating high QoL). Because of clustering of multiples within families, adjusted linear regressions with generalized estimating equations were used to compare ICSI- and naturally conceived adolescents. Missing values were treated by multiple imputation. Minimal importance was defined as half a standard deviation. RESULTS: Both ICSI and control adolescents had high PH (low mean 'total difficulties' score: 9 of 40) and high QoL (mean 'total KINDL' score: 75 of 100). Differences were generally in favour of the ICSI group. Significant differences occurred for 'impact of behavioural problems' (p = 0.033), the 'total KINDL' score (p = 0.021) and the dimensions 'physical wellbeing' (p = 0.031) and 'school' (p = 0.005), but all differences were far below minimal importance. About 80% of ICSI adolescents were informed about their mode of conception. PH and QoL were slightly higher in informed adolescents; behavioural difficulties ('total behavioural problems' and 'conduct problems') were significantly lower (p = 0.013 and p = 0.003), behavioural strengths ('prosocial behaviour') and 'physical QoL' significantly higher (p = 0.004 and p = 0.018), but differences remained clearly below minimal importance. CONCLUSIONS: Our results are reassuring for parents using ICSI and their children. Speaking openly about an ICSI conception in the family may be beneficial.

Myo1g is required for efficient adhesion and migration of activated B lymphocytes to inguinal lymph nodes.

Cell migration is a dynamic process that involves adhesion molecules and the deformation of the moving cell that depends on cytoskeletal remodeling and actin-modulating proteins such as myosins. In this work, we analyzed the role of the class I Myosin-1 g (Myo1g) in migratory processes of LPS + IL-4 activated B lymphocytes in vivo and in vitro. In vivo, the absence of Myo1g reduced homing of activated B lymphocytes into the inguinal lymph node. Using microchannel chambers and morphology analysis, we found that the lack of Myo1g caused adhesion and chemotaxis defects. Additionally, deficiency in Myo1g causes flaws in adopting a migratory morphology. Our results highlight the importance of Myo1g during B cell migration.

H2A.Z overexpression suppresses senescence and chemosensitivity in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most intractable and devastating malignant tumors. Epigenetic modifications such as DNA methylation and histone modification regulate tumor initiation and progression. However, the contribution of histone variants in PDAC is unknown. Here, we demonstrated that the histone variant H2A.Z is highly expressed in PDAC cell lines and PDAC patients and that its overexpression correlates with poor prognosis. Moreover, all three H2A.Z isoforms (H2A.Z.1, H2A.Z.2.1, and H2A.Z.2.2) are highly expressed in PDAC cell lines and PDAC patients. Knockdown of these H2A.Z isoforms in PDAC cell lines induces a senescent phenotype, cell cycle arrest in phase G2/M, increased expression of cyclin-dependent kinase inhibitor CDKN2A/p16, SA-ß-galactosidase activity and interleukin 8 production. Transcriptome analysis of H2A.Z-depleted PDAC cells showed altered gene expression in fatty acid biosynthesis pathways and those that regulate cell cycle and DNA damage repair. Importantly, depletion of H2A.Z isoforms reduces the tumor size in a mouse xenograft model in vivo and sensitizes PDAC cells to gemcitabine. Overexpression of H2A.Z.1 and H2A.Z.2.1 more than H2A.Z.2.2 partially restores the oncogenic phenotype. Therefore, our data suggest that overexpression of H2A.Z isoforms enables cells to overcome the oncoprotective barrier associated with senescence, favoring PDAC tumor grow and chemoresistance. These results make H2A.Z a potential candidate as a diagnostic biomarker and therapeutic target for PDAC.

mTORC1 Prevents Epithelial Damage During Inflammation and Inhibits Colitis-Associated Colorectal Cancer Development.

Epithelial cells lining the intestinal mucosa constitute a selective-semipermeable barrier acting as first line of defense in the organism. The number of those cells remains constant during physiological conditions, but disruption of epithelial cell homeostasis has been observed in several pathologies. During colitis, epithelial cell proliferation decreases and cell death augments. The mechanism responsible for these changes remains unknown. Here, we show that the pro-inflammatory cytokine IFNγ contributes to the inhibition of epithelial cell proliferation in intestinal epithelial cells (IECs) by inducing the activation of mTORC1. Activation of mTORC1 in response to IFNγ was detected in IECs present along the crypt axis and in colonic macrophages. mTORC1 inhibition enhances cell proliferation, increases DNA damage in IEC. In macrophages, mTORC1 inhibition strongly reduces the expression of pro-inflammatory markers. As a consequence, mTORC1 inhibition exacerbated disease activity, increased mucosal damage, enhanced ulceration, augmented cell infiltration, decreased survival and stimulated tumor formation in a model of colorectal cancer CRC associated to colitis. Thus, our findings suggest that mTORC1 signaling downstream of IFNγ prevents epithelial DNA damage and cancer development during colitis.

Cortactin deficiency causes increased RhoA/ROCK1-dependent actomyosin contractility, intestinal epithelial barrier dysfunction, and disproportionately severe DSS-induced colitis.

The intestinal epithelium constitutes a first line of defense of the innate immune system. Epithelial dysfunction is a hallmark of intestinal disorders such as inflammatory bowel diseases (IBDs). The actin cytoskeleton controls epithelial barrier integrity but the function of actin regulators such as cortactin is poorly understood. Given that cortactin controls endothelial permeability, we hypothesized that cortactin is also important for epithelial barrier regulation. We found increased permeability in the colon of cortactin-KO mice that was accompanied by reduced levels of ZO-1, claudin-1, and E-cadherin. By contrast, claudin-2 was upregulated. Cortactin deficiency increased RhoA/ROCK1-dependent actomyosin contractility, and inhibition of ROCK1 rescued the barrier defect. Interestingly, cortactin deficiency caused increased epithelial proliferation without affecting apoptosis. KO mice did not develop spontaneous colitis, but were more susceptible to dextran sulfate sodium colitis and showed severe colon tissue damage and edema formation. KO mice with colitis displayed strong mucus deposition and goblet cell depletion. In healthy human colon tissues, cortactin co-localized with ZO-1 at epithelial cell contacts. In IBDs patients, we observed decreased cortactin levels and loss of co-localization with ZO-1. Thus, cortactin is a master regulator of intestinal epithelial barrier integrity in vivo and could serve as a suitable target for pharmacological intervention in IBDs.

14-3-3 Proteins regulate Akt Thr308 phosphorylation in intestinal epithelial cells.

Akt activation has been associated with proliferation, differentiation, survival and death of epithelial cells. Phosphorylation of Thr308 of Akt by phosphoinositide-dependent kinase 1 (PDK1) is critical for optimal stimulation of its kinase activity. However, the mechanism(s) regulating this process remain elusive. Here, we report that 14-3-3 proteins control Akt Thr308 phosphorylation during intestinal inflammation. Mechanistically, we found that IFNγ and TNFα treatment induce degradation of the PDK1 inhibitor, 14-3-3η, in intestinal epithelial cells. This mechanism requires association of 14-3-3ζ with raptor in a process that triggers autophagy and leads to 14-3-3η degradation. Notably, inhibition of 14-3-3 function by the chemical inhibitor BV02 induces uncontrolled Akt activation, nuclear Akt accumulation and ultimately intestinal epithelial cell death. Our results suggest that 14-3-3 proteins control Akt activation and regulate its biological functions, thereby providing a new mechanistic link between cell survival and apoptosis of intestinal epithelial cells during inflammation.

[Are speed cameras able to reduce traffic noise disturbances? An intervention study in Luebeck]. / Reduktion der Lärmbelästigung durch Geschwindigkeitsmessanlagen? Eine Interventionsstudie in Lübeck.

BACKGROUND: Disturbance by traffic noise can result in health problems in the long run. However, the subjective perception of noise plays an important role in their development. OBJECTIVES: The aim of this study was to determine if speed cameras are able to reduce subjective traffic noise disturbance of residents of high-traffic roads in Luebeck? METHODS: In August 2012 a speed camera has been installed in 2 high-traffic roads in Luebeck (IG). Residents living 1.5 km in front of the installed speed cameras and behind them received a postal questionnaire to evaluate their subjective noise perception before (t0), 8 weeks (t1) and 12 months (t2) after the installation of the speed camera. As controls (CG) we asked residents of another high-traffic road in Luebeck without speed cameras and residents of 2 roads with several consecutive speed cameras installed a few years ago. Furthermore, objective measures of the traffic noise level were conducted. RESULTS: Response rates declined from 35.9% (t0) to 27.2% (t2). The proportion of women in the CG (61.4-63.7%) was significantly higher than in the IG (53.7-58.1%, p<0.05), and responders were significantly younger (46.5±20.5-50±22.0 vs. 59.1±17.0-60.5±16.9 years, p<0.05). A reduction of the perceived noise disturbance of 0.2 point, measured on a scale from 0 (no disturbance) to 10 (heavy disturbance), could be observed in both IG and CG. Directly asked, 15.2% of the IG and 19.3% of the CG reported a traffic noise reduction at t2. The objective measure shows a mean reduction of 0.6 dB at t1. CONCLUSION: The change of noise level of 0.6 dB, which could only be experienced by direct comparison, is in line with the subjective noise perception. As sole method to reduce traffic noise (and for health promotion) a speed camera is insufficient.

[Screening for colorectal, skin, breast and prostate cancer. Essential knowledge for counseling]. / Screening auf Kolorektal-, Haut-, Brust- und Prostatakrebs. Basiswissen für die Beratung.

The major goal of cancer screening programs is the reduction of disease-specific mortality by detecting malignant tumors in an early and still curable stage. Sensitive screening tests are used in apparently healthy people and conspicuous findings are referred for further investigations. Taking the personal disease risk into account, persons considering participation in a screening program should be informed about the methods, benefits and disadvantages of the screening program. This information, together with personal preferences, is the basis for a well-informed decision for or against participation in a screening program. This article imparts essential knowledge that is needed for individual medical counseling on screening for colorectal, skin, breast and prostate cancer.

[Reasons for non-participation in mammography screening--a survey in Schleswig-Holstein, Germany]. / Gründe für die Nicht-Teilnahme am Mammographie-Screening--eine Querschnittsuntersuchung aus Schleswig-Holstein.

BACKGROUND: In 2007, an organized population-based mammography screening program in Schleswig-Holstein has been implemented. According the European guideline a participation rate of 70% should be reached as a measurement of quality. In Schleswig-Holstein participation rate reached only 45% and is one of the lowest rates in Germany. The reasons are unknown. METHOD: To 20,000 women, aged 50-69, who did not participate in mammography screening after an invitation letter, a questionnaire was sent to assess reasons of non-participation and knowledge about the program. We calculated the proportion of women answering to given aspects in the questionnaire. RESULTS: The response rate was 14.8% (n = 2591). Women reported multiple reasons for non-participation. Medical reasons and personal attitude were the most frequent ones. Organizational reasons were of minor importance. 75% of women get primarily informed about the program by the invitation letter. 25% of women talked with their practitioner about the program. CONCLUSION: The low participation rate of mammography screening in Schleswig-Holstein is not based on worse organization but on medical reasons or personal attitudes of the women. It seems, that information about the program and benefits and harms of mammography screening has not reached the general population. So general practitioner or gynecologists should advice women more intensively. Leaflets and pamphlets should be more disseminated.

Colorectal cancer incidence in Germany: stage-shift 6 years after implementation of a colonoscopy screening program.

BACKGROUND: In 2002, colonoscopy was introduced as a tool for colorectal cancer screening in Germany. The long-term objective was to reduce the incidence in colorectal cancer (CRC) by detection and removal of advanced adenomas. Currently, the effect of colonoscopy screening on the population-based incidence of CRC in Germany is unknown. METHODS: We provide data on stage-specific (age-standardized) incidence rates in three federal states in Germany, 6 years after the implementation of colonoscopy. RESULTS: Between 2002 and 2008 a statistically significant decrease in CRC incidence could be observed (annually 3.0%, 95% confidence interval [CI]: -3.8; -2.2). The decline could be observed in all advanced tumor categories (T2, T3, and T4), whereas the incidence of in situ carcinomas (Tis) increased annually by 51.6% (95% CI: 28.0; 79.4) until 2004, and remained stable until 2008. CONCLUSION: The observed changes cannot be attributed definitively to the screening activities, but the presented data support a possible causal association.

Therapeutic Index (TIX) for intranasal corticosteroids in the treatment of allergic rhinitis.

BACKGROUND: Intranasal corticosteroids (INS) are the first line treatment for allergic rhinitis (AR). To guide clinical decision-making, we created a therapeutic index (TIX) for INS reflecting efficacy and safety. METHODS: A Medline search (1966 to June 2009) was carried out to identify all placebo-controlled randomized trials, and observational reports for safety issues, with Dexamethasone, Budesonide (BUD), Fluticasone propionate (FP), Fluticasone furoate (FF), Flunisolide, Mometasone furoate (MF), Triamcinolone (TRIAM), and Beclomethasone dipropionate (BDP) as treatment for AR. Data on three efficacy (nasal symptoms, ocular symptoms, global assessment) and three safety outcomes (epistaxis, growth, systemic ocular effects) were extracted. Meta analyses were performed for each INS and outcome and results were categorised into scores by quartiles. Scores of the three efficacy and safety outcomes were summed up to create summation scores for efficacy (ES) and side effects (AES), respectively with a maximum of 9 points. The TIX was then defined as the ratio of ES and AES. RESULTS: Data of 84 studies were extracted. Based on availability of data, a TIX was calculated for 6 substances. BUD showed the highest efficacy score followed by MF and TRIAM. The lowest scores for side effects were achieved by MF and TRIAM followed by FP. These findings resulted in TIX scores of 7 and 5 for MF and TRIAM, respectively, indicating a high efficacy and low potential of adverse events. Medium scores were reached by BUD and FP and lower scores by BDP and FF. CONCLUSION: Although safety and efficacy is proven for all available INS by multiple studies, the systematic aggregation and analysis of data allows for a differentiated summary on clinically important features.

Development and evaluation of an implementation strategy for the German guideline on community-acquired pneumonia.

BACKGROUND: Data of the German Competence Network for Community-Acquired Pneumonia showed a gap between the recommendations of the national guideline for management of community-acquired pneumonia (CAP) and the routine care. We developed and evaluated an implementation strategy to improve the quality of care of patients with CAP. METHOD: A prospective, randomised, controlled trail was conducted within CAPNETZ. In four local clinical centres (LCC), the guideline was implemented by different strategies. The other four LCC served as control group. Indicators for guideline adherence comprised initial site of treatment, initial antibiotic treatment and duration of antibiotic treatment. As patient-related factors, we assessed the effect of guideline implementation on 30-day mortality and length of hospital stay. RESULTS: Active guideline implementation yielded an increased proportion of guideline adherence to the length of antibiotic treatment in outpatients (+9.2%), the recommended antibiotic treatment (+5.6%) and duration of antibiotic treatment in inpatients (+5.0%) compared with baseline. In contrast, the proportion of patients in the control group, treated according to the guideline, decreased in the same period by 7.9%, 2.9% and 4.7%, respectively. None of these results was statistically significant. Decrease of CAP-related mortality was higher in the intervention group compared with the control group (2.9% vs 0.5%, ns). CONCLUSION: This study showed improvements in the process of care after implementation of a guideline for treating CAP. Further strategies, such as quality improvement cycles and medical practice audits, may enhance this effect.

[Systemic manifestations and comorbidities in patients with chronic obstructive pulmonary disease (COPD) and their effect on clinical state and course of the disease--an overview of the cohort study COSYCONET]. / Einfluss systemischer Manifestationen und Komorbiditäten auf den klinischen Zustand und den Verlauf bei COPD. Eine Ubersicht über die Kohortenstudie COSYCONET.

BACKGROUND AND RATIONALE: The integrated project COSYCONET, as part of the competence network ASCONET funded by the BMBF, has the aim to investigate the relationship between the pulmonary disorder, comorbidities and systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) by adopting cross-sectional as well as longitudinal analyses. METHODOLOGICAL APPROACH: COSYCONET includes a number of projects addressing the issue of comorbidities at the basic science level. Its core project, however, is the establishment of a cohort of patients with COPD, which is compared with two population-based control cohorts. The COPD cohort will include 3,000 patients, among them 1,500 with severity according to GOLD category I/II and 1,500 with category III/IV. Patients will be recruited in study centers covering all major regions of Germany, and this will be achieved in close cooperation with pneumologists from private practices. After recruitment, patients will be studied upon an initial visit as well as 6 and 18 months later. Each visit includes a comprehensive battery of functional tests and questionnaires that aim at assessing the state of the disease as accurately and completely as feasible, comprising lung function and the individual pattern and risk factors of comorbidities including cardiovascular disorders, metabolic disorders, osteoporosis, exercise capacity, acticity and mental status. In addition blood samples will be taken and asservated in a biobank in order to assess markers of systemic inflammation and aging as well as organ-specific markers. Moreover morphological information on the lung as available from HR-CT pictures that have not been specifically taken for the study will be analysed semi-quantitatively in a central facility and standardised manner.

Impact of intravenous {beta}-lactam/macrolide versus {beta}-lactam monotherapy on mortality in hospitalized patients with community-acquired pneumonia.

OBJECTIVES: Guidelines recommend dual-therapy consisting of a beta-lactam/macrolide (BLM) for hospitalized patients with community-acquired pneumonia. Nevertheless, the superiority over beta-lactam-monotherapy (BL) remains unproven. METHODS: Analyses from an observational study initiated by the German competence network CAPNETZ were performed. RESULTS: One thousand eight hundred and fifty-four patients were treated with either BL (49.0%) or BLM (51.0%). BLM therapy was associated with lower adjusted 14 day mortality [odds ratio (OR) 0.53; 95% confidence interval (CI): 0.30-0.94]. CRB65, neoplastic disease, age and nursing home residency were confirmed as independent predictors of death. Adjusted 14 day mortality risk was clearly reduced in patients with CRB65 = 2 (n = 411; OR 0.35; CI: 0.12-0.99) and CRB65 > or = 2 (n = 519; OR 0.42; CI: 0.18-0.997). However, this could not be shown for adjusted 30 day mortality. Patients with CRB65 < or = 1 showed low mortality (2.1%) without the influence of BLM. BLM therapy was associated with lower adjusted risk of treatment failure at 14 days (n = 1854; OR 0.65; CI: 0.47-0.89) and 30 days (OR 0.69; CI: 0.51-0.94) as well as in the subgroup of patients with CRB65 = 2 and CRB65 > or = 2. CONCLUSIONS: This study suggests the superiority of BLM therapy in patients with CRB65 risk classes of 2 or higher on 14 day mortality. BLM therapy was also associated with lower risk of treatment failure.

Guanylate-binding protein-1 is expressed at tight junctions of intestinal epithelial cells in response to interferon-gamma and regulates barrier function through effects on apoptosis.

Guanylate-binding protein-1 (GBP-1) is an interferon inducible large GTPase involved in endothelial cell proliferation and invasion. In this report, expression and function of GBP-1 were investigated in vitro in intestinal epithelia after exposure to interferon-gamma and in human colonic mucosa from individuals with inflammatory bowel disease (IBD). Interestingly, in contrast to other epithelia, GBP-1 distributed to the plasma membrane in intestinal epithelial cells where it colocalized with the tight junction protein coxsackie- and adenovirus receptor. In addition, expression of GBP-1 was upregulated in colonic epithelia of individuals with IBD. Downregulation of GBP-1 by siRNA resulted in enhanced permeability that correlated with increased apoptosis. Indeed, inhibition of caspase activity prevented the inhibition of barrier formation induced by the loss of GBP-1. These data suggest that GBP-1 is a novel marker of intestinal mucosal inflammation that may protect against epithelial apoptosis induced by inflammatory cytokines and subsequent loss of barrier function.

Determinants of influenza and pneumococcal vaccination in elderly people: a systematic review.

OBJECTIVES: Despite strong national and international recommendations on immunization practices, rates for influenza (IV) and pneumococcal vaccinations (PV) are low. We aimed to review international immunization rates and to analyze attitudes and beliefs regarding IV and PV. STUDY DESIGN: Systematic review. METHOD: The MEDLINE database search comprised articles from 1966 to October 2005. Fourteen surveys evaluating a total number of 49292 participants in nine different countries were included into the analysis. RESULTS: Vaccination rates among risk groups do vary significantly between different countries, reaching highest rates in the USA (IV, 82%; PV, 71%) and lowest in former West-Germany for IV (37%) and in Israel for PV (20%). Recommendations by doctors play a central role in promoting IV and PV. The main reason for not being vaccinated was lack of information. CONCLUSION: Specific strategies targeted at groups are needed to increase the knowledge of IV and PV, and thereby decrease incidences of acute lung diseases.

Risk factors for community-acquired pneumonia in German adults: the impact of children in the household.

The objective of this case-control study was to identify the main risk factors for community-acquired pneumonia (CAP) in a German adult population. A self-administered questionnaire was given to CAP cases provided by the German competence network CAPNETZ and population-based, randomly selected controls (sex- and age-matched). Multivariate analysis showed that in addition to known risk factors such as previous CAP [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.3-2.1], more than one respiratory infection during the previous year (OR 3.6, 95% CI 2.9-4.5), chronic pulmonary diseases (OR 2.3, 95% CI 1.7-3.0), number of comorbidities (OR 1.6, 95% CI 1.4-1.9), and number of children in the household (2 children: OR 2.2, 95% CI 1.5-3.4; > or = 3 children: OR 3.2, 95% CI 1.5-7.0) were independent risk factors for CAP. This was pronounced in particular in people aged < or = 65 years. The most likely explanation for this finding is higher exposure to infectious agents.

[Results of a comparison: active versus passive reporting in cases of community acquired pneumonia. Results of the German Competence Network CAPNETZ]. / Ergebnisvergleich: Aktives versus passives Meldesystem bei Fällen mit ambulant erworbener Pneumonie. Ergebnisse aus dem Kompetenznetzwerk CAPNETZ.

INTRODUCTION: Since 2002, the German competence network CAPNETZ has been collecting data from inpatients and outpatients with community acquired pneumonia (CAP) at eight local clinical centres. Contrary to the literature reports, the proportion of outpatients in CAPNETZ averages out at 28 %. Therefore, this study determines whether an active reporting system can increase the number of cases reported in medical practices. METHOD: In ten medical practices in Lübeck, the passive reporting system was changed to an active reporting system consisting of a) a weekly announcement of CAP cases including negative reporting, b) a study nurse who was responsible for the reporting, c) additional payment, d) a telephone call after two weeks by absent announcements and e) incentives like benchmarking or additional information. The number of the reported cases between the active reporting period (2004) and the same period in the year before was recorded. RESULTS: The number of reported cases increased in eight of the ten medical practices. Overall 72 CAP cases were reported, 33 % more than in the period of passive reporting. The number of patients encompassed in CAPNETZ increased from 17 to 34. CONCLUSION: We did not find a comparable increase of CAP cases either in Lübeck overall (including inpatients) or in all the local clinical centres together. Thus, it is assumed that the increase of reported cases depends on the methodical effect.

Recombinant erythropoietin for the treatment of anemia in inflammatory bowel disease.

BACKGROUND: Some patients with inflammatory bowel disease have anemia that is refractory to treatment with iron and vitamins. We examined whether administering iron and recombinant erythropoietin could raise hemoglobin levels in such patients. METHODS: Thirty-four patients with inflammatory bowel disease (15 with ulcerative colitis and 19 with Crohn's disease) and anemia refractory to iron therapy (hemoglobin concentrations below 10.0 g per deciliter [6.2 mmol per liter]) were randomly assigned in a prospective, double-blind, 12-week trial to receive either oral iron (100 mg per day) and subcutaneous erythropoietin (150 U per kilogram of body weight twice per week) (n=17) or oral iron and placebo (n=17). The primary measure of efficacy was an increase in hemoglobin levels of more than 1.0 g per deciliter (0.62 mmol per liter). Additional analyses were performed with other patients with inflammatory bowel disease. RESULTS: The severity of anemia was related to clinical disease activity as well as to in vitro monocyte secretion of interleukin-1 beta, a proinflammatory cytokine. Serum erythropoietin concentrations were increased in 52 randomly selected outpatients with inflammatory bowel disease and anemia, but the concentrations were inadequate in relation to the degree of anemia. Twelve weeks of therapy with recombinant erythropoietin and oral iron increased mean (+/-SE) hemoglobin concentrations from 8.81+/-0.27 g per deciliter (5.47+/-0.17 micromol per liter) to 10.52+/-0.41 g per deciliter (6.5+/-0.25 micromol per liter), whereas hemoglobin concentrations in the placebo group decreased from 8.69+/-0.11 g per deciliter (5.4+/-0.068 micromol per liter) to 7.84+/- 0.33 g per deciliter (4.9+/-0.2 mmol per liter) (P<0.001). After 12 weeks, hemoglobin levels had increased by more than 1.0 g per deciliter in 82 percent of the patients in the erythropoietin group, as compared with 24 percent of those in the placebo group (P=0.002). There were five treatment failures in the placebo group and two in the erythropoietin group (P=0.18); treatment failure was defined as a decrease in hemoglobin levels of more than 2.0 g per deciliter (1.24 micromol per liter) to a value below 8.0 g per deciliter (4.96 micromol per liter) or any decrease to less than 6.5 g per deciliter (4.03 micromol per liter). CONCLUSIONS: In patients with inflammatory bowel disease and anemia refractory to treatment with iron and vitamins, treatment with oral iron and recombinant erythropoietin can raise hemoglobin levels.