Measuring Intracompartmental Pressures in the Lower Leg: Assessing the Use of Unilateral Measurements in Patients with Bilateral Symptoms.

The purpose of the present study was to evaluate whether unilateral intracompartmental pressure (ICP) measurements correctly represent the contralateral ICP value in patients suspected to have bilateral chronic exertional compartment syndrome (CECS) in the anterior compartment of the leg. Methods: A retrospective cohort study was performed that included military service members who had been referred to a secondary care department for bilateral anterolateral exercise-related leg pain. The obtained ICP values were utilized to assess 2 possible measurement strategies to perform unilateral ICP measurements: the right-leg strategy (i.e., always testing the right leg) and the most-symptomatic-leg strategy (i.e., always testing the most symptomatic). The diagnostic cutoff value for CECS in this cohort was 35 mmHg in the first minute after provocation. Four outcome categories were created to describe the pressure classification of the second leg if only 1 leg would have been measured: correct (category 1: both values ≥35 mmHg; category 2: both values <35 mmHg) or incorrect (category 3: measured leg, ≥35 mmHg and contralateral leg, <35 mmHg; category 4: measured leg, <35 mmHg and contralateral leg, ≥35 mmHg). Results: A total of 442 patients (884 legs) were included. In 88% of patients, the unilateral value would have correctly diagnosed the other symptomatic leg, whereas in 12% of patients, the contralateral leg would have been diagnosed incorrectly. The right-leg strategy had a slightly smaller proportion of cases in which the contralateral leg would have been incorrectly diagnosed (7% compared with 8% for the most symptomatic leg strategy). In 89% of the 390 patients in categories 1 and 2, the ICP values deviated by >5 mmHg from the 35-mmHg cutoff value compared with 40% of the 52 patients in categories 3 and 4. Conclusions: In military service members with bilateral chronic anterolateral exertional pain, a unilateral ICP measurement seems to be justified, especially among those with pressure values >5 mmHg above or below the diagnostic cutoff value. When a unilateral pressure measurement is within 5 mmHg above or below the cutoff value, a bilateral ICP measurement may be warranted. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Presence of CD163+ macrophages in DCD kidneys with high DGF reduces the risk for acute cellular rejection in 6 months after kidney transplantation.

Acute cellular rejection (ACR) occurs in 10% of renal allograft recipients and is characterized by leukocyte infiltration as observed in needle biopsies. ACR onset is subject to several risk factors, including delayed graft function (DGF). As the impact of DGF on the etiology of ACR remains unclear, this study analyzed the association between presence of leukocyte subsets and ACR onset, in DCD kidney biopsies with extensive DGF following transplantation. Immunohistochemical analysis of protocol biopsies taken 10 days after kidney transplantation revealed that patients with high levels of renal CD163+ macrophages have a decreased risk (OR = 0.021, P = 0.008) for ACR in the first 6 months after transplantation. In pre-transplant biopsies of a comparable DCD cohort, with >80% DGF, presence of donor CD163+ macrophages showed no effect on ACR risk. Therefore, leukocyte infiltrate present during the inflammatory response at the time of DGF may contain anti-inflammatory macrophages that exert a protective effect against ACR development.

The evolution of mammalian brain size.

Relative brain size has long been considered a reflection of cognitive capacities and has played a fundamental role in developing core theories in the life sciences. Yet, the notion that relative brain size validly represents selection on brain size relies on the untested assumptions that brain-body allometry is restrained to a stable scaling relationship across species and that any deviation from this slope is due to selection on brain size. Using the largest fossil and extant dataset yet assembled, we find that shifts in allometric slope underpin major transitions in mammalian evolution and are often primarily characterized by marked changes in body size. Our results reveal that the largest-brained mammals achieved large relative brain sizes by highly divergent paths. These findings prompt a reevaluation of the traditional paradigm of relative brain size and open new opportunities to improve our understanding of the genetic and developmental mechanisms that influence brain size.

Data for a city-level health impact assessment of urban transport in Mauritius.

Participatory quantitative Health Impact Assessments (HIAs) in developing countries are rare partly due to data scarcity. This paper reports on primary data collected in the city of Port Louis to complete a HIA of urban transport planning in Mauritius. We conducted a full-chain participatory HIA to assess health impacts on the basis of a transport mode shift in Port Louis, Mauritius [1]. By applying mixed-methods, we estimated averted deaths per year and economic outcomes by assessing the health determinants of air pollution, traffic deaths and physical activity. The participatory quantitative HIA included [1] baseline data collection [2] co-validation of transport policy scenarios with stakeholders and [3] quantitative modelling of health impacts. We used the risk assessment method for HIA appraisal. The data can be reused for epidemiological analysis and different types of impact assessments.

Effectiveness of pulmonary rehabilitation at high-altitude compared to sea-level in adults with severe refractory asthma.

BACKGROUND: Beneficial effects of pulmonary rehabilitation at high-altitude (HAPR) in patients with severe refractory asthma have been reported earlier, but evidence for the effectiveness is limited. AIM: To investigate the effectiveness of high-altitude pulmonary rehabilitation to comparable treatment at sea-level (LAPR) on patient outcome parameters. METHODS: Adults with severe refractory asthma living in The Netherlands were included. Treatment consisted of a 12-week personalized multidisciplinary rehabilitation program either at high-altitude (Davos Switzerland) (n = 93) or in a tertiary lung center at sea-level in The Netherlands (n = 45). At baseline, after treatment, and during 12 months follow-up asthma related quality of life (AQLQ), asthma control (ACQ), pulmonary function and OCS-dose were assessed. Patients could not be randomized resulting in different asthma populations. Groups were compared using linear regression analysis (ANCOVA) adjusted for baseline values, in addition to age, atopy, smoking history, BMI and gender. RESULTS: After treatment, and at 12 months follow-up, improved AQLQ(0.92,p < 0.001 and 0.82,p = 0.001, respectively), ACQ(-0.87,p < 0.001 and -0.69,p = 0.008, respectively) and lower maintenance OCS dose (Unadjusted linear regression analysis-5.29 mg, p = 0.003 and Crude Odds Ratio-1.67, p = 0.003, respectively) were observed in the HAPR-group compared to the LAPR group. Patients receiving HAPR also had less asthma exacerbations (≥1 exacerbation: 20% vs 60%,p < 0.001) and showed improvement in lung function (%predFEV1 3.4%,p = 0.014) compared to the LAPR group, but at 12 months no differences between groups were observed. CONCLUSION: HAPR resulted in a larger improvement in patient outcome parameters compared to LAPR, on the long run the improvement in patient reported symptoms and lower maintenance OCS-dose persists. Underlying factors that explain this observed effect need to be investigated.

Participatory quantitative health impact assessment of urban transport planning: A case study from Eastern Africa.

BACKGROUND: High rates of motorization in urban areas of Africa have adverse effects on public health. Transport-related mortality will increase as a result of inadequate transport infrastructure, air pollution and sedentary lifestyles. Health Impact Assessments (HIAs) have proven to be a successful tool to predict and mitigate negative health impact of urban transport planning policies, programmes or projects. Yet, there is a gap of evidence on transport and health in African countries. The aim of this study is assessing the health impacts of transport scenarios in Port Louis (city of 119,018 inhabitants in Mauritius) using a full chain participatory HIA model. METHODS: We estimated health and economic impacts associated to transport scenarios with qualitative data and quantitative comparative risk assessment methods. The health impact modeling was based on differences between the baseline and three transport scenarios (worse, good, ideal), estimating the averted deaths per year and economic outcomes by assessing health determinants of air pollution (AP), traffic deaths and physical activity (PA). Data on air pollution and traffic fatalities were obtained from public data sources. Data used to construct scenarios, establish baseline travel mode shares and physical activity were collected through (a) open-ended individual interviews (IDIs) with 14 stakeholders (b) closed-ended survey questions to 600 citizens and (c) 2 focus group discussions (FGDs) with the same 14 stakeholders from (a). RESULTS: In Port Louis, the worse-case transport scenario (doubling in car trips and a reduction in walking, motorcycle, and public transport), resulted in a total increment of 3.28 premature deaths per year. The good-case scenario (reducing car trips by half and increasing walking, motorcycle, and public transport trips) resulted in a total increment of 0.79 premature deaths per year. The ideal-case scenario (reduction in car and motorcycle trips and an increase in walking and public transport trips) resulted in a total reduction of 13.72 premature deaths per year. We estimated USD 23 millions of economic benefits related to mortality if the ideal-case was achieved. CONCLUSION: Participatory HIA shows that implementing transport policies aiming for less than an ideal situation may not be adequate or sufficient to avoid negative transport-related mortality in Mauritius. Urban transport planning is an opportunity to encourage physical activity in rapidly urbanizing settings of Africa. Transport policies should aim to restrict all forms of private motorized vehicles and promote active and public transport to support public health. We highly recommend the use of participatory approaches in quantitative HIA to ensure context specificity and policy relevance.

The single-cell eQTLGen consortium.

In recent years, functional genomics approaches combining genetic information with bulk RNA-sequencing data have identified the downstream expression effects of disease-associated genetic risk factors through so-called expression quantitative trait locus (eQTL) analysis. Single-cell RNA-sequencing creates enormous opportunities for mapping eQTLs across different cell types and in dynamic processes, many of which are obscured when using bulk methods. Rapid increase in throughput and reduction in cost per cell now allow this technology to be applied to large-scale population genetics studies. To fully leverage these emerging data resources, we have founded the single-cell eQTLGen consortium (sc-eQTLGen), aimed at pinpointing the cellular contexts in which disease-causing genetic variants affect gene expression. Here, we outline the goals, approach and potential utility of the sc-eQTLGen consortium. We also provide a set of study design considerations for future single-cell eQTL studies.

Absolute Bioavailability and Pharmacokinetic Comparability of Sirukumab Following Subcutaneous Administration by a Prefilled Syringe or an Autoinjector.

This phase 1, randomized, open-label study assessed the absolute bioavailability and pharmacokinetic comparability of sirukumab, a human anti-interleukin-6 monoclonal antibody, following subcutaneous (SC) administration via Prefilled Syringe-UltraSafe Passive® Delivery System (PFS-U) or Prefilled Syringe-SmartJect® Autoinjector (PFS-AI; Janssen Research & Development, LLC, Spring House, Pennsylvania). A total of 144 healthy male subjects were randomized to 5 single-dose treatment groups: sirukumab 50 mg and 100 mg (each by PFS-U and PFS-AI) and sirukumab 100 mg intravenous (IV) infusion. Pharmacokinetic parameters were calculated using noncompartmental analysis. Following SC administration, maximum serum concentrations (Cmax ) and area under the concentration-vs-time curve (AUC) increased in an approximately dose-proportional manner. Median time to reach Cmax was 5 days, and mean half-life ranged from 16 to 19 days. Mean absolute bioavailability of sirukumab by PFS-AI and PFS-U, respectively, was estimated at 92.4% and 81.4% with 100 mg and 88.4% and 94.7% with 50 mg. Ratios of geometric means (90% confidence intervals) of Cmax and AUC0-77d for PFS-AI:PFS-U were 1.13 (1.03, 1.25) and 1.14 (1.05, 1.24), respectively, indicating comparable systemic exposures of sirukumab following a single 100-mg SC dose by PFS-U or PFS-AI. The incidence of antibodies to sirukumab was low (1.4%). No new safety concerns associated with sirukumab were identified at either dose.

Physics of IED Blast Shock Tube Simulations for mTBI Research.

Shock tube experiments and simulations are conducted with a spherical gelatin filled skull-brain surrogate, in order to study the mechanisms leading to blast induced mild traumatic brain injury. A shock tube including sensor system is optimized to simulate realistic improvised explosive device blast profiles obtained from full scale field tests. The response of the skull-brain surrogate is monitored using pressure and strain measurements. Fluid-structure interaction is modeled using a combination of computational fluid dynamics (CFD) simulations for the air blast, and a finite element model for the structural response. The results help to understand the physics of wave propagation, from air blast into the skull-brain. The presence of openings on the skull and its orientation does have a strong effect on the internal pressure. A parameter study reveals that when there is an opening in the skull, the skull gives little protection and the internal pressure is fairly independent on the skull stiffness; the gelatin shear stiffness has little effect on the internal pressure. Simulations show that the presence of pressure sensors in the gelatin hardly disturbs the pressure field.

FIB-SEM cathodoluminescence tomography: practical and theoretical considerations.

Focused ion beam-scanning electron microscope (FIB-SEM) tomography is a powerful application in obtaining three-dimensional (3D) information. The FIB creates a cross section and subsequently removes thin slices. The SEM takes images using secondary or backscattered electrons, or maps every slice using X-rays and/or electron backscatter diffraction patterns. The objective of this study is to assess the possibilities of combining FIB-SEM tomography with cathodoluminescence (CL) imaging. The intensity of CL emission is related to variations in defect or impurity concentrations. A potential problem with FIB-SEM CL tomography is that ion milling may change the defect state of the material and the CL emission. In addition the conventional tilted sample geometry used in FIB-SEM tomography is not compatible with conventional CL detectors. Here we examine the influence of the FIB on CL emission in natural diamond and the feasibility of FIB-SEM CL tomography. A systematic investigation establishes that the ion beam influences CL emission of diamond, with a dependency on both the ion beam and electron beam acceleration voltage. CL emission in natural diamond is enhanced particularly at low ion beam and electron beam voltages. This enhancement of the CL emission can be partly explained by an increase in surface defects induced by ion milling. CL emission enhancement could be used to improve the CL image quality. To conduct FIB-SEM CL tomography, a recently developed novel specimen geometry is adopted to enable sequential ion milling and CL imaging on an untilted sample. We show that CL imaging can be manually combined with FIB-SEM tomography with a modified protocol for 3D microstructure reconstruction. In principle, automated FIB-SEM CL tomography should be feasible, provided that dedicated CL detectors are developed that allow subsequent milling and CL imaging without manual intervention, as the current CL detector needs to be manually retracted before a slice can be milled. Due to the required high electron beam acceleration voltage for CL emission, the resolution for FIB-SEM CL tomography is currently limited to several hundreds of nm in XY and up to 650 nm in Z for diamonds. Opaque materials are likely to have an improved Z resolution, as CL emission generated deeper in the material is not able to escape from it.

Donor brain death predisposes human kidney grafts to a proinflammatory reaction after transplantation.

Donor brain death has profound effects on post-transplantation graft function and survival. We hypothesized that changes initiated in the donor influence the graft's response to ischemia and reperfusion. In this study, human brain dead donor kidney grafts were compared to living and cardiac dead donor kidney grafts. Pretransplant biopsies of brain dead donor kidneys contained notably more infiltrating T lymphocytes and macrophages. To assess whether the different donor conditions result in a different response to reperfusion, local cytokine release from the reperfused kidney was studied by measurement of paired arterial and renal venous blood samples. Reperfusion of kidneys from brain dead donors was associated with the instantaneous release of inflammatory cytokines, such as G-CSF, IL-6, IL-9, IL-16 and MCP-1. In contrast, kidneys from living and cardiac dead donors showed a more modest cytokine response with release of IL-6 and small amounts of MCP-1. In conclusion, this study shows that donor brain death initiates an inflammatory state of the graft with T lymphocyte and macrophage infiltration and massive inflammatory cytokine release upon reperfusion. These observations suggest that brain dead donors require a novel approach for donor pretreatment aimed at preventing this inflammatory response to increase graft survival.

[Providing oral healthcare to frail older people who wear complete dentures. No place for standard treatments]. / Zorgverlening aan kwetsbare ouderen met volledige gebitsprothesen. Geen plaats voor standaardbehandelingen.

Frail older people who wear complete dentures may have denture-related complaints which are more pronounced due to their somatic, psychological and/or social problems. On the other hand, it often happens that serious complaints are not or cannot be expressed. In those cases, members of the individual's social network or care providers may request treatment. According to the authors' experience, managing technical denture disorders by carrying out standard treatments or inserting oral implants is not always successful. Basic principles of providing oral healthcare to frail older people are: restraint in carrying out treatments, avoiding standard treatments, taking into consideration the limited adaptability of older people, continuous awareness of one's own functioning in the decision-making process, and paying attention to the role of family members, voluntary and professional care providers, and physicians.

[Effects of recollecting autobiographical memories on the emotional well-being of older adults]. / Effecten van het ophalen van autobiografische herinneringen op emotioneel welbevinden bij ouderen.

This experiment examined the effect of different ways of recollecting autobiographical memories on emotional well-being. Participants between 65 and 80 years old (N = 70) were instructed to write about a memory from their life when they were 15 to 30 years old. They were asked to do this in a narrative way about a positive memory, in a narrative way about a negative memory or in an interpretative way about a negative memory. We also examined whether spontaneous reminiscence types in everyday life moderate the effects of the experimental manipulation on emotional well-being. Narrating positive memories is more favourable for negative affect than narrating or interpreting negative memories. There is no moderating role for everyday reminiscence types, even though these are related to emotional well-being. Manipulated and spontaneous reminiscence are therefore different. This is a favourable finding for reminiscence interventions, because they can stimulate positive memories, no matter how older people are used to memorize their past.

Systematic review: the effects of conservative and surgical treatment for obesity on gastro-oesophageal reflux disease.

BACKGROUND: Incidence rates of both obesity and gastro-oesophageal reflux disease (GERD) are increasing, particularly in the Western world. It has been suggested that GERD symptoms may be improved by weight reduction. AIM: To review the literature on the effect of various weight reducing modalities on manifestations of GERD in obese patients. METHODS: A literature search was performed using PubMed, EMBASE and the Cochrane Library, combining the words obesity and gastro-oesophageal reflux with bariatric surgery, diet, lifestyle intervention and weight loss. RESULTS: With regard to diet/lifestyle intervention (conservative), four of seven studies reported an improvement of GERD. For Roux-en-Y gastric bypass, a positive effect on GERD was found in all studies, although this was mainly evaluated by questionnaires. In contrast, for vertical banded gastroplasty, no change or even an increase of GERD was noted, whereas the results for laparoscopic adjustable gastric banding were conflicting. CONCLUSIONS: Dietary and lifestyle intervention may improve GERD in obese patients; however, the most favourable effect is likely to be found after bariatric surgery, especially after Roux-en-Y gastric bypass. Future studies need to elucidate for which GERD patients laparoscopic adjustable gastric banding might have a beneficial effect and how they can be identified preoperatively.

Oesophageal acid hypersensitivity is not a contraindication to Nissen fundoplication.

BACKGROUND: The Rome III criteria classify patients with a positive relationship between symptoms and reflux episodes but a physiological oesophageal acid exposure time as having gastro-oesophageal reflux disease (GORD) with an acid hypersensitive oesophagus. The long-term outcome of antireflux surgery in these patients was investigated. METHODS: Outcomes of Nissen fundoplication in 28 patients with GORD refractory to proton-pump inhibitors (PPIs) and oesophageal acid hypersensitivity (group 1) were compared with those of 126 patients with pathological acid exposure (group 2). RESULTS: Fundoplication had a similar effect in both groups. Three months after surgery, total acid exposure time and the prevalence of oesophagitis had decreased, whereas mean lower oesophageal pressure had increased. The percentage of patients using PPIs was reduced from 83 to 4 per cent in group 1 and from 86.1 to 7.4 per cent in group 2 (both P < 0.001). Quality of life measured on a scale from 0 to 100 improved from 52 to 69 (P = 0.009) and 64 (P < 0.001) respectively. The percentage of patients with resolved or improved symptoms at 5 years was similar. CONCLUSION: Patients with oesophageal acid hypersensitivity benefit from Nissen fundoplication as much as those with pathological acid exposure.

Early renal ischemia-reperfusion injury in humans is dominated by IL-6 release from the allograft.

The pathophysiology of ischemia/reperfusion (I/R) injury is complex, and current knowledge of I/R injury in humans is incomplete. In the present study, human living-donor kidney transplantation was used as a highly reproducible model to systematically study various processes potentially involved in early I/R injury. Unique, direct measurements of arteriovenous concentration differences over the kidney revealed massive release of interleukin (IL)-6 in the first 30 minutes of graft reperfusion and a modest release of IL-8. Among the assessed markers of oxidative and nitrosative stress, only 15(S)-8-iso-PGF(2alpha) was released. When assessing cell activation, release of prothrombin factor 1 + 2 indicated thrombocyte activation, whereas there was no release of markers for endothelial activation or neutrophil activation. Common complement activation complex sC5b-9 was not released into the bloodstream, but was released into urine rapidly after reperfusion. To investigate whether IL-6 plays a modulating role in I/R injury, a mouse experiment of renal I/R injury was performed. Neutralizing anti-IL-6 antibody treatment considerably worsened kidney function. In conclusion, this study shows that renal I/R in humans is dominated by local IL-6 release. Neutralization of IL-6 in mice resulted in a significant aggravation of renal I/R injury.

In GERD patients, mucosal repair associated genes are upregulated in non-inflamed oesophageal epithelium.

Previous studies addressing the effects of acid reflux and PPI therapy on gene expression in oesophageal epithelium concentrated on inflamed tissue. We aimed to determine changes in gene expression in non-inflamed oesophageal epithelium of GERD patients. Therefore, we included 20 GERD patients with pathological total 24-hr acid exposure of 6-12% and SAP > or = 95%. Ten patients discontinued PPI treatment (PPI-), 10 took pantoprazole 40 mg bid (PPI+). Ten age/sex-matched healthy controls were recruited. Biopsies were taken from non-inflamed mucosa 6 cm and 16 cm proximal to the squamocolumnar junction (SCJ). Gene expression profiling of biopsies from 6 cm was performed on Human Genome U133 Plus 2.0 arrays (Affymetrix). Genes exhibiting a fold change >1.4 (t-test P-value < 1(E)- 4) were considered differentially expressed. Results were confirmed by real-time RT-PCR. In PPI- patients, 92 microarray probesets were deregulated. The majority of the corresponding genes were associated with cell-cell contacts, cytoskeletal reorganization and cellular motility, suggesting facilitation of a migratory phenotype. Genes encoding proteins with anti-apoptotic or anti-proliferative functions or stress-protective functions were also deregulated. No probesets were deregulated in PPI+ patients. QPCR analysis of 20 selected genes confirmed most of the deregulations in PPI- patients, and showed several deregulated genes in PPI+ patients as well. In the biopsies taken at 16 cm QPCR revealed no deregulations of the selected genes. We conclude that upon acid exposure, oesophageal epithelial cells activate a process globally known as epithelial restitution: up-regulation of anti-apoptotic, anti-oxidant and migration associated genes. Possibly this process helps maintaining barrier function.

Patients with physiological acid exposure and positive symptom association scores: a distinct group within the GORD spectrum.

Studies comparing pH-metrically well-characterized gastro-oesophageal reflux disease (GORD) patients with physiological reflux to GORD patients with pathological reflux, with regard to clinical and epidemiological data, are lacking. We included 273 GORD patients with pathological 24-h pH-monitoring (pH+), defined as pH<4 > or = 6% of time. A symptom index (SI) > or = 50% was considered positive, as well as a symptom association probability (SAP) > or = 95%. We included 84 GORD patients with physiological acid exposure (pH-) and a positive SI and/or SAP. Manometry and endoscopy reports were reviewed. Subjects completed questionnaires about demographics and medical history, functional dyspepsia and irritable bowel syndrome, the Nepean Dyspepsia Index symptom score and the RAND-36 quality of life scale. pH- patients were younger (45 vs 50 years, P = 0.003), more often female (60%vs 39%, P = 0.001), smoked more (31%vs 19%, P = 0.021) and reported proton pump inhibition failure more often (47%vs 32%, P = 0.027). A hypotensive lower oesophageal sphincter was less common in pH- patients (18%vs 34%, P = 0.008) and distal oesophageal contraction amplitude was higher (11 vs 9.5 kPa, P = 0.045). pH- patients had hiatal hernia and oesophagitis less often (48%vs 73%, P < 0.0005; 36%vs 54%, P = 0.012 respectively). pH- patients less often reported no other symptoms besides GORD (20%vs 34%, P = 0.015). pH- patients scored worse at the Nepean (reflux 19 vs 12 out of 39, P < 0.0005; dyspepsia 54 vs 38 out of 156, P < 0.0005). In the subgroup of patients who have physiological oesophageal acid exposure the enhancement of the perceived symptom burden appears to be the most important mechanism in GORD pathogenesis.

Gastroesophageal reflux disease is associated with the C825T polymorphism in the G-protein beta3 subunit gene (GNB3).

OBJECTIVES: Visceral hypersensitivity is involved in the etiology of reflux symptoms. Familial clustering and twin studies demonstrated a genetic predisposition to gastroesophageal reflux disease (GERD). G-protein-coupled receptors (GPCRs) mediate the response to acid, neurotransmitters and humoral factors modulating esophageal sensory function. Thus, polymorphisms in G-proteins are putative genetic factors contributing to GERD manifestation. A functional polymorphism in the G-protein beta3 subunit gene (GNB3) is associated with functional dyspepsia (FD), in which visceral hypersensitivity is implicated in symptom generation. We evaluated the association of the GNB3 C825T polymorphism with GERD and GERD subgroups classified according to esophageal acid exposure time, symptom-reflux correlation, or coexistence of FD and/or irritable bowel syndrome (IBS) symptoms. METHODS: In total, 363 GERD patients, defined as having esophageal pH < 4 > or = 6% of time and/or symptom index (SI) > or = 50% or symptom association probability (SAP) > or = 95%, participated. In addition, 373 healthy controls free of gastrointestinal symptoms were studied. Genotyping was performed by molecular beacon assay. RESULTS: The CT genotype was more prevalent in GERD patients relative to healthy controls (adjusted odds ratio (OR)=1.43, 95% CI 1.04-1.98). GERD patients sensitive to physiological amounts of reflux displayed a higher OR (1.59), as did GERD patients with a positive symptom association score (1.50). The strongest association was detected in patients without concomitant FD and/or IBS symptoms (OR=1.66). CONCLUSIONS: GERD is associated with GNB3 C825T. The results for GERD subgroups support the hypothesis that enhanced perception of reflux events, as a consequence of the increased signal transduction upon GPCR activation associated with the 825T allele, underlies this association.

Validation of a disease-specific quality-of-life questionnaire in a large sample of Dutch achalasia patients.

SUMMARY: The aim of this study was to validate a translated version of an achalasia-specific quality-of-life questionnaire (achalasia-DSQoL) by examining its psychometric properties in a Dutch cohort of achalasia patients. The achalasia-DSQoL was administered to 171 treated achalasia patients together with a clinical symptom score and the RAND-36. Validation methods included factor analysis, known-group techniques, Cronbach's alpha and Spearman rank correlation with other questionnaires and feasibility. About 72.5% of the achalasia patients completed the questionnaires. The achalasia-DSQoL showed evidence of an underlying construct and seems reliable with a Cronbach's alpha of 0.77. The question concerning heartburn did not correlate with the other items on the questionnaire. Known-group techniques demonstrated that the achalasia-DSQoL discriminates between achalasia patients in clinical remission and patients who are not. There was a moderate correlation between the achalasia-DSQoL and the RAND-36 subscales. The questionnaire was easy in use. The translated version of the achalasia-DSQoL is a valid and reliable instrument to compare groups of achalasia patients although the question concerning heartburn should be excluded.