Morphology of the Esophageal Hiatus: Is It Different in 3 Types of Hiatus Hernias?

Background/aimsThe esophageal hiatus is formed by the right crus of the diaphragm in the majority of subjects. Contraction of the hiatus exerts a sphincter-like action on the lower esophageal sphincter (LES). The aim is to study the hiatal anatomy (using CT scan imaging) and function (using high-resolution manometry [HRM]), and esophageal motor function in patients with sliding and paraesophageal hiatal hernia.MethodsWe assessed normal subjects (n = 20), patients with sliding type 1 hernia (n = 18), paraesophageal type 2 hernia (n = 19), and mixed type 3 hernia (n = 19). Hernia diagnosis was confirmed on the upper gastrointestinal series. The hiatal morphology was constructed from the CT scan images. The LES pressure and relaxation, percent peristalsis, bolus pressure, and hiatal squeeze pressure were assessed by HRM.ResultsThe CT images revealed that the esophageal hiatus is formed by the right crus of the diaphragm in all normal subjects and 86% of hernia patients. The hiatus is elliptical in shape with a surface area of 1037 mm2 in normal subjects. The hiatal dimensions were larger in patients compared to normal subjects. The HRM revealed impaired LES relaxation and higher bolus pressure in patients with paraesophageal compared to the sliding hernia. The hiatal pinch on HRM was recognized in significantly higher number of patients with sliding as compared to paraesophageal hernia.ConclusionsUsing a novel approach, we provide details of the esophageal hiatus in patients with various kinds of hiatal hernia. Impaired LES relaxation in paraesophageal hernia may play a role in its pathophysiology and genesis of symptoms

Artifact Rejection Methodology Enables Continuous, Noninvasive Measurement of Gastric Myoelectric Activity in Ambulatory Subjects.

The increasing prevalence of functional and motility gastrointestinal (GI) disorders is at odds with bottlenecks in their diagnosis, treatment, and follow-up. Lack of noninvasive approaches means that only specialized centers can perform objective assessment procedures. Abnormal GI muscular activity, which is coordinated by electrical slow-waves, may play a key role in symptoms. As such, the electrogastrogram (EGG), a noninvasive means to continuously monitor gastric electrical activity, can be used to inform diagnoses over broader populations. However, it is seldom used due to technical issues: inconsistent results from single-channel measurements and signal artifacts that make interpretation difficult and limit prolonged monitoring. Here, we overcome these limitations with a wearable multi-channel system and artifact removal signal processing methods. Our approach yields an increase of 0.56 in the mean correlation coefficient between EGG and the clinical "gold standard", gastric manometry, across 11 subjects (p < 0.001). We also demonstrate this system's usage for ambulatory monitoring, which reveals myoelectric dynamics in response to meals akin to gastric emptying patterns and circadian-related oscillations. Our approach is noninvasive, easy to administer, and has promise to widen the scope of populations with GI disorders for which clinicians can screen patients, diagnose disorders, and refine treatments objectively

Spatial Patterns From High-Resolution Electrogastrography Correlate With Severity of Symptoms in Patients With Functional Dyspepsia and Gastroparesis.

Background & aimsInvasive gastric electrical mapping has revealed spatial abnormalities of the slow wave in subjects with gastroparesis and functional gastrointestinal disorders. Cutaneous high-resolution electrogastrography (HR-EGG) is a non-invasive method that can detect spatial features of the gastric slow wave. We performed HR-EGG in subjects with active foregut symptoms to evaluate associations between gastric myoelectric abnormalities, symptoms (based on a validated questionnaire), and gastric emptying.MethodsWe performed a case-control study of 32 subjects, including 7 healthy individuals (controls), 7 subjects with functional dyspepsia and normal gastric emptying, and 18 subjects with gastroparesis, from a tertiary care program. All subjects were assessed by computed tomography imaging of the abdomen and HR-EGG and completed the PAGI-SYM questionnaire on foregut symptoms, which includes the gastroparesis cardinal symptom index. We performed volume reconstruction of the torso and stomach from computed tomography images to guide accurate placement of the HR-EGG array.ResultsSpatial slow-wave abnormalities were detected in 44% of subjects with foregut symptoms. Moreover, subjects with a higher percentage of slow waves with aberrant propagation direction had a higher total gastroparesis cardinal symptom index score (r = 0.56; P < .001) and more severe abdominal pain (r = 0.46; P = .009). We found no correlation between symptoms and traditional EGG parameters.ConclusionsIn case-control study, we found that the genesis of symptoms of functional dyspepsia and gastroparesis is likely multifactorial, including possible contribution from gastric myoelectric dysfunction. Abnormal spatial parameters, detected by cutaneous HR-EGG, correlated with severity of upper gastrointestinal symptoms, regardless of gastric emptying. This noninvasive, repeatable approach might be used to identify patients for whom gastric myoelectric dysfunction contributes to functional dyspepsia and gastroparesis

Strain System for the Motion Base Shuttle Mission Simulator

The Motion Base Shuttle Mission Simulator (MBSMS) Strain System is an innovative engineering tool used to monitor the stresses applied to the MBSMS motion platform tilt pivot frames during motion simulations in real time. The Strain System comprises hardware and software produced by several different companies. The system utilizes a series of strain gages, accelerometers, orientation sensor, rotational meter, scanners, computer, and software packages working in unison. By monitoring and recording the inputs applied to the simulator, data can be analyzed if weld cracks or other problems are found during routine simulator inspections. This will help engineers diagnose problems as well as aid in repair solutions for both current as well as potential problems

Quality Control of Pre-1948 Cooperative Observer Network Data

A recent comprehensive effort to digitize U.S. daily temperature and precipitation data observed prior to 1948 has resulted in a major enhancement in the computer database of the records of the National Weather Service’s cooperative observer network. Previous digitization efforts had been selective, concentrating on state or regional areas. Special quality control procedures were applied to these data to enhance their value for climatological analysis. The procedures involved a two-step process. In the first step, each individual temperature and precipitation data value was evaluated against a set of objective screening criteria to flag outliers. These criteria included extreme limits and spatial comparisons with nearby stations. The following data were automatically flagged: 1) all precipitation values exceeding 254 mm (10 in.) and 2) all temperature values whose anomaly from the monthly mean for that station exceeded five standard deviations. Addi- tional values were flagged based on differences with nearby stations; in this case, metrics were used to rank outliers so that the limited resources were concentrated on those values most likely to be invalid. In the second step, each outlier was manually assessed by climatologists and assigned one of the four following flags: valid, plausible, questionable, or invalid. In excess of 22 400 values were manually assessed, of which about 48% were judged to be invalid. Although additional manual assessment of outliers might further improve the quality of the database, the procedures applied in this study appear to have been successful in identifying the most flagrant errors

Requirement for PCNA in DNA Mismatch Repair at a Step Preceding DNA Resynthesis

Abstractid system was used to screen yeast and human expression libraries for proteins that interact with mismatch repair proteins. PCNA was recovered from both libraries and shown in the case of yeast to interact with both MLH1 and MSH2. A yeast strain containing a mutation in the PCNA gene had a strongly elevated mutation rate in a dinucleotide repeat, and the rate was not further elevated in a strain also containing a mutation in MLH1. Mismatch repair activity was examined in human cell extracts using an assay that does not require DNA repair synthesis. Activity was inhibited by p21 WAF1 or a p21 peptide, both of which bind to PCNA, and activity was restored to inhibited reactions by addition of PCNA. The data suggest a PCNA requirement in mismatch repair at a step preceding DNA resynthesis. The ability of PCNA to bind to MLH1 and MSH2 may reflect linkage between mismatch repair and replication and may be relevant to the roles of mismatch repair proteins in other DNA transactions

Ethanol Feeding Impairs Innate Immunity and Alters the Expression of Th1- and Th2-Phenotype Cytokines in Murine Klebsiella Pneumonia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65658/1/j.1530-0277.1998.tb04303.x.pd

A Two Micron All-Sky Survey View of the Sagittarius Dwarf Galaxy: II. Swope Telescope Spectroscopy of M Giant Stars in the Dynamically Cold Sagittarius Tidal Stream

We present moderate resolution (~6 km/s) spectroscopy of 284 M giant candidates selected from the Two Micron All Sky Survey photometry. Radial velocities (RVs) are presented for stars mainly in the south, with a number having positions consistent with association to the trailing tidal tail of the Sagittarius (Sgr) dwarf galaxy. The latter show a clear RV trend with orbital longitude, as expected from models of the orbit and destruction of Sgr. A minimum 8 kpc width of the trailing stream about the Sgr orbital midplane is implied by verified RV members. The coldness of this stream (dispersion ~10 km/s) provides upper limits on the combined contributions of stream heating by a lumpy Galactic halo and the intrinsic dispersion of released stars, which is a function of the Sgr core mass. The Sgr trailing arm is consistent with a Galactic halo containing one dominant, LMC-like lump, however some lumpier halos are not ruled out. An upper limit to the total M/L of the Sgr core is 21 in solar units. A second structure that roughly mimics expectations for wrapped, leading Sgr arm debris crosses the trailing arm in the Southern Hemisphere; however, this may also be an unrelated tidal feature. Among the <13 kpc M giants toward the South Galactic Pole are some with large RVs that identify them as halo stars, perhaps part of the Sgr leading arm near the Sun. The positions and RVs of Southern Hemisphere M giants are compared with those of southern globular clusters potentially stripped from the Sgr system and support for association of Pal 2 and Pal 12 with Sgr debris is found. Our discussion includes description of a masked-filtered cross-correlation methodology that achieves better than 1/20 of a resolution element RVs in moderate resolution spectra.Comment: 41 pages, 6 figures, Astronomical Journal, in press (submitted Nov. 24, 2003; tentatively scheduled for July 2004 issue

Comparative RNA editing in autistic and neurotypical cerebella

Adenosine-to-inosine (A-to-I) RNA editing is a neurodevelopmentally regulated epigenetic modification shown to modulate complex behavior in animals. Little is known about human A-to-I editing, but it is thought to constitute one of many molecular mechanisms connecting environmental stimuli and behavioral outputs. Thus, comprehensive exploration of A-to-I RNA editing in human brains may shed light on gene–environment interactions underlying complex behavior in health and disease. Synaptic function is a main target of A-to-I editing, which can selectively recode key amino acids in synaptic genes, directly altering synaptic strength and duration in response to environmental signals. Here, we performed a high-resolution survey of synaptic A-to-I RNA editing in a human population, and examined how it varies in autism, a neurodevelopmental disorder in which synaptic abnormalities are a common finding. Using ultra-deep (>1000 × ) sequencing, we quantified the levels of A-to-I editing of 10 synaptic genes in postmortem cerebella from 14 neurotypical and 11 autistic individuals. A high dynamic range of editing levels was detected across individuals and editing sites, from 99.6% to below detection limits. In most sites, the extreme ends of the population editing distributions were individuals with autism. Editing was correlated with isoform usage, clusters of correlated sites were identified, and differential editing patterns examined. Finally, a dysfunctional form of the editing enzyme adenosine deaminase acting on RNA B1 was found more commonly in postmortem cerebella from individuals with autism. These results provide a population-level, high-resolution view of A-to-I RNA editing in human cerebella and suggest that A-to-I editing of synaptic genes may be informative for assessing the epigenetic risk for autism.Nancy Lurie Marks Family FoundationF. Hoffmann-La Roche & Co. (Applied Science Sequencing Grant Program)Autism Speaks (Organization)Simons FoundationNational Institutes of Health (U.S.) (Grant 1R01MH085143-01