Understanding demand for, and feasibility of, centre-based child-care for poor urban households: a mixed methods study in Dhaka, Bangladesh.

BACKGROUND: Centre-based child-care has potential to provide multiple health and development benefits to children, families and societies. With rapid urbanisation, increasing numbers of low-income women work with reduced support from extended family, leaving a child-care vacuum in many low- and middle-income countries. We aimed to understand perceptions of, and demand for, centre-based child-care in Dhaka, Bangladesh among poor, urban households, and test the feasibility of delivering sustainable centre-based child-care. METHODS: We used sequential mixed methods including a household survey (n = 222) and qualitative interviews with care-givers (n = 16), community leaders (n = 5) and policy-makers (n = 5). We co-produced and piloted a centre-based child-care model over ten-months, documenting implementation. A co-design focus group with mothers, parents' meetings, and qualitative interviews with child-care centre users (n = 5), non-users (n = 3), ex-users (n = 3) and staff (2) were used to refine the model and identify implementation issues. RESULTS: We found 24% (95% CI: 16,37%) of care-givers reported turning-down paid work due to lack of child-care and 84% (95% CI:74, 91%) reported wishing to use centre-based child-care and were willing to pay up to 283 Takka (~$3.30) per month. Adjusted odds of reported need for child-care among slum households were 3.8 times those of non-slum households (95% CI: 1.4, 10). Implementation highlighted that poor households needed free child-care with food provided, presenting feasibility challenges. Meta-inference across quantitative and qualitative findings identified the impact of the urban environment on child-care through long working hours, low social capital and fears for child safety. These influences interacted with religious and social norms resulting in caution in using centre-based child-care despite evident need. CONCLUSION: Sustainable provision of centre-based care that focuses on early childhood development requires subsidy and careful design sensitive to the working lives of poor families, particularly women and must respond to the dynamics of the urban environment and community values. We recommend increased research and policy focus on the evaluation and scale-up of quality centre-based child-care, emphasising early-childhood development, to support low-income working families in urban areas.

Conjunctivitis in dupilumab clinical trials.

BACKGROUND: Dupilumab blocks the shared receptor component for interleukin (IL)-4 and IL-13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate-to-severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate-to-severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate-to-severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo. OBJECTIVES: To characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials. METHODS: We evaluated randomized placebo-controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47). RESULTS: In most AD trials, dupilumab-treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators. In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase the incidence compared with placebo. In the EoE trial, no patients had conjunctivitis. CONCLUSIONS: Conjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the incidence of conjunctivitis was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab-treated patients require further study. What's already known about this topic? Ocular disorders, including allergic conjunctivitis, are common in patients with atopic dermatitis (AD). In most dupilumab AD trials, dupilumab-treated patients had higher conjunctivitis incidence than those receiving placebo. Most cases were mild to moderate and recovered or were recovering during study treatment; study treatment discontinuation due to conjunctivitis was rare. Conjunctivitis incidence was very low and similar for dupilumab and placebo in clinical trials in asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis. What does this study add? This analysis confirms and extends the results of the individual clinical trials. Baseline disease-related factors, including AD severity, prior conjunctivitis history and certain biomarkers (thymus and activation-regulated chemokine, IgE, eosinophils), were associated with increased incidence of conjunctivitis. Patients who responded well to dupilumab had reduced incidence of conjunctivitis. Further study is needed to elucidate the aetiology and treatment of conjunctivitis in dupilumab-treated patients with AD.

Oral delivery of fluticasone powder improves esophageal eosinophilic inflammation and symptoms in adults with eosinophilic esophagitis.

Topical steroids are the primary medical therapy for eosinophilic esophagitis (EoE). Current steroid formulations are used off-label and designed for airway delivery. It is known that the efficacy of topical steroids depends on drug-mucosal contact time, which is related to its formulation. The purpose of this study is to examine the effectiveness of fluticasone administered by means of an orally administered powder formulation. We conducted a retrospective analysis of patients diagnosed with EoE based on current guidelines and who were treated with orally administered fluticasone powder. The primary outcome was histologic response (peak eosinophil density (eos/hpf)). Secondary outcomes included patient-reported symptoms (EoEQ) and endoscopic features measured by a validated instrument (EoE endoscopic reference score, EREFS). Forty patients were treated with fluticasone powder with doses of 500 to 1000 mcg b.i.d. A significant difference was found between pre- and posttreatment levels of eosinophilia (P < 0.0001). Seventy-five percent of patients achieved peak densities of <15 eos/hpf. Improvement was also demonstrated in dysphagia symptoms (P = 0.031) and endoscopic findings of furrows (P = 0.0001) and exudates (P = 0.0001). Oral fluticasone powder induced significant improvement in histopathology, symptoms, and endoscopic features of inflammation in adults with EoE. It offers an easy-to-administer formulation of a topical steroid that circumvents concerns with esophageal delivery of commonly used, aerosolized inhaler preparations.

Prospective assessment of disease-specific quality of life in adults with eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is an important cause of upper gastrointestinal dysfunction in children and adults. The EoE-quality of life (QOL)-A was validated as a disease-specific measure of quality of life in EoE. This study characterized the extent of QOL concerns in a cohort of adult EoE patients and delineated the relationships between QOL and other disease activity measures. One hundred sixty-seven patients enrolled in this prospective cohort study. Patients with established and suspected EoE undergoing endoscopy at a single university-based medical center were recruited. EoE was diagnosed on the basis of the clinical criteria and histologic demonstration of ≥15 eos/hpf while on proton pump inhibition therapy. Sixty five patients undergoing repeat endoscopy during the enrollment period participated twice. Patients provided demographic information and completed symptom assessments and the EoE-QOL-A. Analyses included comparisons with overall QOL as well as QOL subscales. Outcome measures included endoscopic activity using a validated instrument, the EoE Endoscopic Reference Score, and histology. Overall QOL was significantly correlated with dysphagia frequency, intensity, and severity (P < 0.001). Patients who experienced a food impaction in the last 30 days had significantly worse overall QOL (P = 0.009). There was no correlation between overall QOL and years since diagnosis, symptom duration, endoscopic features, or histologic findings. Patient symptoms correlated with endoscopic features of edema, rings, and stricture severity. Histologic activity was highly correlated with severity of endoscopic features. Patients who underwent repeat endoscopy with histologic response demonstrated improved eating and social QOL; however, overall QOL was unchanged. In adults with EoE, patient reported QOL is associated with symptom severity but not endoscopic or histologic features. Disease-specific QOL may complement parameters of biologic activity in the assessment of overall disease burden in EoE.

Editorial: Reflux While Running: Something to Belch About.

Running is the most popular form of exercise in the United States. Gastroesophageal reflux (GER) is common during exercise and may affect performance. Previous studies have focused on increased intra-abdominal pressure as a major determinant of acid reflux during physical exertion. In this issue, Herregods et al. examined the mechanisms of GER in healthy volunteers using simultaneous high-resolution manometry and pH impedance testing performed while running. Novel observations afforded by the utilization of state-of-the-art technology include the importance of transient lower esophageal sphincter relaxation ("belch reflex") and transient formation of hiatal hernia during exercise. The findings are provocative and lend credence to commonsense strategies to minimize the consequences of belching in runners.

Evaluation of esophageal distensibility in eosinophilic esophagitis: an update and comparison of functional lumen imaging probe analytic methods.

BACKGROUND: Distensibility evaluation of the esophageal body using the functional lumen imaging probe (FLIP) offers an objective measure to characterize patients with eosinophilic esophagitis (EoE), though this analysis may be limited by unrecognized catheter movement and esophageal contractility. The aims of this study were to report novel FLIP analytic methods of esophageal distensibility measurement in EoE and to assess the effect of contractility. METHODS: Nine healthy controls (six female; ages 20-49) and 20 EoE patients (four female; ages 19-64; grouped by degree of distension-mediated contractility identified on FLIP) were evaluated with a 16-cm FLIP device during step-wise balloon distension during upper endoscopy. A distensibility plateau (DP) was generated using multiple methods to identify the narrowest esophageal body diameter: (i) wavelet decomposition (WD), (ii) maximal diameter (MD), and (iii) FLIP Analytics software. KEY RESULTS: Distensibility was reduced in EoE patients compared with controls using the WD (p = 0.002) and MD (p = 0.001) methods; a trend was detected using the FLIP Analytics method (p = 0.055). Significant intra-subject differences were detected between methods among both patients and controls (p-values <0.001 to 0.025); the difference was more pronounced among subjects with a greater degree of contractility. DP was <19 mm among 7/9 controls with FLIP Analytics, 6/9 controls with WD, and 0/9 controls using the MD method. CONCLUSIONS & INFERENCES: Distension-mediated contractility affects distensibility measurement with the FLIP. Using software-based algorithms, particularly with a method that identifies the maximal-achieved diameters (MD), may improve objective distensibility measurement for clinical research and practice.

Prospective assessment of the diagnostic utility of esophageal brushings in adults with eosinophilic esophagitis.

Patients with eosinophilic esophagitis (EoE) undergo multiple endoscopies with biopsy for both diagnosis and assessment of treatment response, which is inconvenient and costly. Brush cytology has been examined in Barrett's esophagus to reduce the need for repeated endoscopic biopsies. The aim of this pilot study was to evaluate the ability of brush cytology to detect mucosal eosinophilia in patients with EoE. This prospective study included adults with untreated and treated esophageal eosinophilia undergoing endoscopy at a tertiary care center. Patients received paired brushings and biopsies at the proximal and distal esophagus. A blinded pathologist quantified the number of eosinophils and epithelial cells per high-power field (hpf) on the cytology slides. The ratio of eosinophils/epithelial cells was used to normalize the cytology specimens for density of cells collected. The main outcome measures were sensitivity and specificity of brush cytology, and correlation between cytology and histology. Twenty-eight patients enrolled. The average age of the cohort was 37.7 ± 10.4 years; 75% of subjects were male. The sensitivity of cytology was 67-69% at the proximal esophagus and 70-72% at the distal esophagus. The specificity was 61-67% proximally and 70-75% distally. Histology was not significantly correlated with the max ratio of eosinophils/epithelial cells per hpf or the absolute number of eosinophils on cytology slides. Cytology using esophageal brushing has limited sensitivity and specificity for the detection of esophageal mucosal eosinophilia. The presence of exudates on endoscopy increased the detection of eosinophilia, which could make cytology useful in pediatric EoE, which often has a more exudative presentation. Diagnostic yield may improve with alternative acquisition techniques or the incorporation of eosinophil degranulation proteins.

Eosinophilic oesophagitis: relationship of quality of life with clinical, endoscopic and histological activity.

BACKGROUND: Knowledge about determinants of quality of life (QoL) in eosinophilic oesophagitis (EoO) patients helps to identify patients at risk of experiencing poor QoL and to tailor therapeutic interventions accordingly. AIM: To evaluate the impact of symptom severity, endoscopic and histological activity on EoE-specific QoL in adult EoE patients. METHODS: Ninety-eight adult EoE patients were prospectively included (64% male, median age 39 years). Patients completed two validated instruments to assess EoE-specific QoL (EoO-QoL-A) and symptom severity (adult EoE activity index patient-reported outcome) and then underwent esophagogastroduodenoscopy with biopsy sampling. Physicians reported standardised information on EoE-associated endoscopic and histological alterations. The Spearman's rank correlation coefficient was calculated to determine the relationship between QoL and symptom severity. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms, endoscopic and histological findings explain variations in QoL. RESULTS: Quality of life strongly correlated with symptom severity (r = 0.610, P < 0.001). While the variation in severity of symptoms, endoscopic and histological findings alone explained 38%, 35% and 22% of the variability in EoE-related QoL, respectively, these together explained 60% of variation. Symptom severity explained 18-35% of the variation in each of the five QoL subscale scores. CONCLUSIONS: Eosinophilic oesophagitis symptom severity and biological disease activity determine QoL in adult patients with eosinophilic oesophagitis. Therefore, reduction in both eosinophilic oesophagitis symptoms as well as biological disease activity is essential for improvement of QoL in adult patients. Clinicaltrials.gov number, NCT00939263.

Practical approach to implementing dietary therapy in adults with eosinophilic esophagitis: the Chicago experience.

Eosinophilic esophagitis (EoE) is a chronic immune/antigen-mediated esophageal disease characterized by esophageal dysfunction and esophageal mucosal eosinophilia. Diet therapy is effective in the treatment of EoE in both children and adults. The role of food allergens is well established in the pathogenesis and treatment of eosinophilic esophagitis. Empiric elimination with a six-food elimination diet (avoiding milk, wheat, egg, soy, peanuts/tree nuts, and fish/shellfish) demonstrates remission in over 70% of adults with this disease. Dietary therapy in adult EoE is becoming more accepted by both patients and clinicians. Dietary therapy can be effectively implemented in clinical practice with appropriate dietary education, patient resources, and close communication with physician and clinical staff. The ability to identify specific food triggers to help tailor dietary therapy for long-term management allows for a return to consumption of most table foods. Furthermore, the diet approach avoids the need for chronic topical corticosteroid use and possible long-term side effects of these medications. The decision to proceed with dietary therapy should be decided by patient preference and available resources. A collaborative and multidisciplinary approach including gastroenterologists, allergists, nurses, and dietitians is essential in the success of this approach.

Development and field testing of a novel patient-reported outcome measure of dysphagia in patients with eosinophilic esophagitis.

BACKGROUND: Dysphagia is the hallmark of eosinophilic esophagitis (EoE), but no validated dysphagia instruments in this population exist. AIM: To develop and field test a patient-reported outcome (PRO) for dysphagia in subjects with EoE. METHODS: This was a multi-centre/multi-phase prospective study. The first phase developed a dysphagia questionnaire using qualitative methods. The second phase was a 30-day field trial to test the instrument and assess content validity. Adolescents and adults with EoE, active symptoms of dysphagia and oesophageal eosinophilia (≥15 eosinophils per high-power field) were enrolled. Solid-food-avoidance days, dysphagia days and actions taken to get relief were recorded. A dysphagia score was calculated and compared to the Straumann Dysphagia Instrument (SDI). RESULTS: Ten adolescents and 10 adults were included in the first phase and the Dysphagia Symptom Questionnaire (DSQ), a three-item daily electronic diary, was developed. In the second phase, 35 subjects finished the field trial (18 adults, 17 adolescents, mean age 24, 54% male, 95% white, 54% currently on topical corticosteroids). The median number of dysphagia days per week was 2 for adolescents vs. 4 for adults (P < 0.001), and 2 for those on topical steroids vs. 4 for those not on topical steroids (P < 0.001). The DSQ score strongly correlated with the number of dysphagia days (R = 0.96; P < 0.001) and the SDI (R = 0.77; P < 0.001). CONCLUSIONS: The DSQ, a three-question patient-reported outcome, was successfully developed and field tested. The DSQ had content validity and the score accurately measured dysphagia frequency and intensity. The Dysphagia Symptom Questionnaire is suitable for use in clinical trials of EoE patients with dysphagia.

Pediatric and adult eosinophilic esophagitis: similarities and differences.

Early in the 1990s, several case series described adults suffering from dysphagia and children with refractory reflux symptoms, both accompanied by an eosinophil-predominant infiltration, thereby conclusively distinguishing it from gastroesophageal reflux disease. Eosinophilic esophagitis (EoE) was recognized as its own entity in the adult and in the pediatric literature. In the last decade, evidence has accumulated that EoE represents a T-helper (Th)2-type inflammatory disease. Remodeling of the esophagus is a hallmark of EoE, leading to esophageal dysfunction and bolus impaction. Familial occurrence and disease association with single-nucleotide polymorphisms underscore the influence of genetics in this disease. Eosinophilic esophagitis may affect individuals at any age, although the clinical presentation is highly age dependent. There is a significant allergic bias in the EoE population, with the majority of patients having concurrent allergic rhinitis, asthma, eczema, and/or a history of atopy. One noteworthy difference is that in children, EoE seems to be primarily a food antigen-driven disease, whereas in adults, mainly aeroallergen sensitization has been observed. Treatment modalities for EoE include the 3Ds: drugs, diet, and dilation. The crucial question of whether adult and pediatric EoE are different phenotypes of one single entity or whether we are confronted with two different diseases is still open. Here, we review similarities and differences between EoE in adults and children.

The adult eosinophilic oesophagitis quality of life questionnaire: a new measure of health-related quality of life.

BACKGROUND: Eosinophilic oesophagitis (EoO) is a chronic disease characterised by significant symptoms and challenging treatment regimens. Health-related quality of life (HRQOL) is a useful way to direct patient care. EoO symptoms and treatment may impact patient HRQOL. Currently, there is no reliable and valid measure of adult EoO patient HRQOL. AIM: To validate the Adult Eosinophilic Oesophagitis Quality of Life (EoO-QOL-A) questionnaire as a measure of HRQOL in this population. METHODS: The EoO patients aged 18-70 recruited via an out-patient GI clinic and two EoO advocacy groups completed the preliminary EoO-QOL-A, demographic and clinical information, and measures of general HRQOL, psychological distress and EoO symptom severity. A subset of patients completed test-retest assessments. Scale reliability, internal consistency, factor structure, concurrent and convergent validity were evaluated. RESULTS: A total of 201 patients have participated. The study sample was primarily Caucasian, college-educated, and evenly split by gender. The average duration of disease was 7 years with duration of symptoms of 26 months prior to diagnosis. Patients reported were using both pharmacological and dietary treatments. Factor analysis yielded a 37-item, 5-factor structure: Eating/Diet Impact, Social Impact, Emotional Impact, Disease Anxiety and Choking Anxiety. The EoO-QOL-A demonstrated excellent internal consistency, split-half and test-retest reliability. Concurrent and convergent validity were supported by moderate correlations with established HRQOL measures, psychological distress and oesophageal symptoms. CONCLUSIONS: The EoO-QOL-A is a valid and reliable disease-specific HRQOL measure for adult EoO patients. Developing the Adult Eosinophilic Oesophagitis Quality of Life is an important step in guiding treatment practices, improving disease education and standardising research protocols.

Use of a continuing medical education course to improve fellows' knowledge and skills in esophageal disorders.

Advanced esophageal endoscopic procedures such as stricture dilation, hemostasis tools, and stent placement as well as high-resolution manometry (HRM) interpretation are necessary skills for gastroenterology fellows to obtain during their training. Becoming proficient in these skills may be challenging in light of higher complication rates compared with diagnostic procedures and infrequent opportunities to practice these skills. Our aim was to determine if intensive training during a continuing medical education (CME) course boosts the knowledge and skills of gastroenterology fellows in esophageal diagnostic test interpretation and performance of therapeutic procedures. This was a pretest-posttest design without a control group of a simulation-based, educational intervention in esophageal stricture balloon dilation and HRM interpretation. The participants were 24 gastroenterology fellows from 21 accredited US training programs. This was an intensive CME course held in Las Vegas, Nevada from August 7 to August 9, 2009. The research procedure had two phases. First, the subjects were measured at baseline (pretest) for their knowledge and procedural skill. Second, the fellows received 6 hours of education sessions featuring didactic content, instruction in HRM indications and interpretation, and deliberate practice using an esophageal stricture dilation model. After the intervention, all of the fellows were retested (posttest). A 17-item checklist was developed for the esophageal balloon dilation procedure using relevant sources, expert opinion, and rigorous step-by-step procedures. Nineteen representative HRM swallow studies were obtained from Northwestern's motility lab and formed the pretest and posttest in HRM interpretation. Mean scores on the dilation checklist improved 81% from 39.4% (standard deviation [SD]= 33.4%) at pretest to 71.3% (SD = 29.5%) after simulation training (P < 0.001). HRM mean examination scores increased from 27.2% (SD = 16.4%) to 46.5% (SD = 15.8%), representing a 71% improvement (P < 0.001). Pearson's correlations indicated there was no correlation between pretest performance, medical knowledge measured by United States Medical Licensing Examination examinations, prior clinical experience, or procedural self-confidence and posttest performance of esophageal dilation or HRM interpretation. The education program was rated highly. This study demonstrated that a CME course significantly enhanced the technical skills and knowledge of gastroenterology fellows in esophageal balloon dilation and HRM interpretation. CME courses such as this may be a valuable adjunct to standard fellowship training in gastroenterology.

Manometric features of eosinophilic esophagitis in esophageal pressure topography.

BACKGROUND: Although most of the patients with eosinophilic esophagitis (EoE) have mucosal and structural changes that could potentially explain their symptoms, it is unclear whether EoE is associated with abnormal esophageal motor function. The aims of this study were to evaluate the esophageal pressure topography (EPT) findings in EoE and to compare them with controls and patients with gastro-esophageal disease (GERD). METHODS: Esophageal pressure topography studies in 48 EoE patients, 48 GERD patients, and 50 controls were compared. The esophageal contractile pattern was described for ten 5-mL swallows for each subject and each swallow was secondarily characterized based on the bolus pressurization pattern: absent, pan-esophageal pressurization, or compartmentalized distal pressurization. KEY RESULTS: Thirty-seven percent of EoE patients were classified as having abnormal esophageal motility. The most frequent diagnoses were of weak peristalsis and frequent failed peristalsis. Although motility disorders were more frequent in EoE patients than in controls, the prevalence and type were similar to those observed in GERD patients (P=0.61, chi-square test). Pan-esophageal pressurization was present in 17% of EoE and 2% of GERD patients while compartmentalized pressurization was present in 19% of EoE and 10% of GERD patients. These patterns were not seen in control subjects. CONCLUSIONS & INFERENCES: The prevalence of abnormal esophageal motility in EoE was approximately 37% and was similar in frequency and type to motor patterns observed in GERD. Eosinophilic esophagitis patients were more likely to have abnormal bolus pressurization patterns during swallowing and we hypothesize that this may be a manifestation of reduced esophageal compliance.

Caffeine and taurine enhance endurance performance.

Caffeine enhances endurance performance; however, its effect on accumulated lactate remains unclear. Conversely, taurine, which also enhances endurance performance, decreases accumulated lactate. In this study, the effect of combination of caffeine and taurine on endurance performance was assessed. Mice ran on a treadmill, and the accumulated lactate was measured. In addition, muscle fibers from the gastrocnemius muscle of the mice were stained with ATPase and analyzed. The use of caffeine and taurine over a 2 week period enhanced endurance performance. Moreover, taurine significantly decreased the accumulated concentration of lactate over long running distances. However, the diameter of the cross-sections and ratios of Types I, IIA, and IIB muscle fibers were not affected.

CMC-544 (inotuzumab ozogamicin), an anti-CD22 immuno-conjugate of calicheamicin, alters the levels of target molecules of malignant B-cells.

We studied the effect of CMC-544, the calicheamicin-conjugated anti-CD22 monoclonal antibody, used alone and in combination with rituximab, analyzing the quantitative alteration of target molecules, that is, CD20, CD22, CD55 and CD59, in Daudi and Raji cells as well as in cells obtained from patients with B-cell malignancies (BCM). Antibody inducing direct antiproliferative and apoptotic effect, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) were tested separately. In Daudi and Raji cells, the CDC effect of rituximab significantly increased within 12 h following incubation with CMC-544. The levels of CD22 and CD55 were significantly reduced (P<0.001 in both cells) after incubation with CMC-544, but CD20 level remained constant or increased for 12 h. Similar results were obtained in cells from 12 patients with BCM. The antiproliferative and apoptotic effect of CMC-544 were greater than that of rituximab. The ADCC of rituximab was not enhanced by CMC-544. Thus, the combination of CMC-544 and rituximab increased the in vitro cytotoxic effect in BCM cells, and sequential administration for 12 h proceeded by CMC-544 was more effective. The reduction of CD55 and the preservation of CD20 after incubation with CMC-544 support the rationale for the combined use of CMC-544 and rituximab.

Review article: modern technology in the diagnosis of gastro-oesophageal reflux disease--Bilitec, intraluminal impedance and Bravo capsule pH monitoring.

Ambulatory pH monitoring detects abnormal levels of acid reflux in the oesophagus and can be used to correlate patients' symptoms with oesophageal acid exposure. Catheter-based pH testing has several limitations, including issues of sensitivity, specificity, tolerability and the inability to record non-acid reflux events. In an effort to improve upon these drawbacks, several devices have been introduced, including the Bilitec system for measuring duodenogastro-oesophageal reflux; intraluminal impedance monitoring, which detects the distribution, composition and clearing of both acid and non-acid oesophageal reflux; and a wireless pH monitoring device, the Bravo capsule. Initial investigations using the Bilitec system demonstrated that duodenogastro-oesophageal reflux tracked very closely with acid reflux and decreased with proton-pump inhibitor (PPI) therapy, casting doubt on the clinical utility of Bilitec monitoring. Recent evidence revealed a possible role for duodenogastro-oesophageal reflux in a subset of patients who continue to report reflux symptoms in the setting of normalized oesophageal acid exposure on high-dose PPI therapy. When combined with pH monitoring, impedance monitoring enhances the detection and characterization of gastro-oesophageal reflux and may have a role in the evaluation of certain specific gastro-oesophageal reflux disease (GERD) symptoms that persist despite acid suppression therapy. The utility of the Bravo wireless technology for GERD diagnosis has been validated in several studies, with improvements over catheter-based pH monitoring in tolerability, accuracy and sensitivity, as well as the ability to record periods both off and on PPI therapy in a single study. All three diagnostic modalities have advanced the understanding of GERD pathogenesis, but their impact on the clinical management of GERD is still the focus of active investigation.