Clinical Practice Guidelines for the Assessment of Uninvestigated Esophageal Dysphagia.

Background And Aims: Our aim is to review the literature and provide guidelines for the assessment of uninvestigated dysphagia.

Methods: A systematic literature search identified studies on dysphagia. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach.

Achalasia-Specific Quality of Life After Pneumatic Dilation or Laparoscopic Heller Myotomy With Partial Fundoplication: A Multicenter, Randomized Clinical Trial.

Objectives: Achalasia is a chronic, progressive, and incurable esophageal motility disease. There is clinical uncertainty about which treatment should be recommended as first-line therapy. Our objective was to evaluate the effectiveness of pneumatic dilation compared with laparoscopic Heller myotomy with partial fundoplication in improving achalasia-specific quality of life.

Identification of dysphagia using the Toronto Bedside Swallowing Screening Test (TOR-BSST©): are 10 teaspoons of water necessary?

Dysphagia screening often includes administration of water. This study assessed the accuracy in identifying dysphagia with each additional teaspoon of water. The original research of the TOR-BSST(©) permitted this assessment.

White matter abnormalities in irritable bowel syndrome and relation to individual factors.

Patients with irritable bowel syndrome (IBS) have abnormal cortical responses to rectal distension and grey matter thinning in brain areas associated with nociception. These abnormalities may be driven by white matter changes and individual factors. Therefore, we tested the hypothesis that WM subserving the pain system is compromised in IBS, and that disease characteristics and personality contribute to these abnormalities.

Interstitial cells of Cajal: pacemaker cells of the pancreatic duct?

Objectives: Ramon y Cajal discovered interstitial cells in the pancreas associated with intrinsic nerves. It was our aim to provide evidence for or against the hypothesis that the pancreatic duct harbors interstitial cells of Cajal (ICCs) that may function as pacemakers for duct motility.

Methods: We used immunohistochemistry using c-Kit as the ICC marker and protein gene product 9.

Nitric oxide activation of a potassium channel (BK(Ca)) in feline lower esophageal sphincter.

Aim: To assess the effect of nitric oxide (NO) on the large conductance potassium channel (BK(Ca)) in isolated circular (CM) and sling (SM) muscle cells and muscle strips from the cat lower esophageal sphincter (LES) to determine its regulation of resting tone and relaxation.

Methods: Freshly enzymatically-digested and isolated circular smooth muscle cells were prepared from each LES region. To study outward K+ currents, the perforated patch clamp technique was employed.

Cognitive factors affect treatment response to medical and psychological treatments in functional bowel disorders.

Objectives: For clinical trials in functional bowel disorders (FBD), the definition of a responder, one who meets the predefined criteria for a clinical response, is needed. Factors that determine clinical response aside from treatment itself are unknown. The aim of this study was to determine what baseline and post-treatment factors affect treatment response.

Altered brain structure in irritable bowel syndrome: potential contributions of pre-existing and disease-driven factors.

Background & Aims: Brain imaging studies have identified abnormal rectal-evoked responses and cortical thinning in patients with irritable bowel syndrome (IBS). However, it is not known whether these abnormalities are pre-existing or develop as result of long-term IBS. Therefore, we tested whether abnormal structural gray matter integrity in IBS correlates with individual disease symptoms, duration of the IBS, or the personality characteristic of pain catastrophizing.

Perceptions of psychological issues related to dysphagia differ in acute and chronic patients.

The objectives of this study were (1) to compare and contrast the psychological issues perceived by patients with oropharyngeal dysphagia and explore if the differences relate to recovery trajectory, and (2) to determine whether patients, caregivers, and clinicians had different perceptions of how psychological issues interacted with the lung and nutrition issues as consequences of dysphagia. Two focus groups (one each of acute and chronic patients) were conducted with a total of 8 participants. Four focus groups (3 with clinicians and 1 with caregivers) were also conducted.

Irritable bowel syndrome subtypes defined by Rome II and Rome III criteria are similar.

Background: The implications of the Rome III recommendations to change the irritable bowel syndrome (IBS) subtype criteria for stool pattern are unknown.

Aim: (1) Determine the level of agreement between Rome II and Rome III subtypes and (2) compare the behaviors of Rome II and Rome III subtypes over time.

Methods: Female patients (n=148) with Rome II defined IBS were prospectively tracked over 5 consecutive 3-month periods.

Not all side effects associated with tricyclic antidepressant therapy are true side effects.

Background & Aims: Patients with functional gastrointestinal disorders treated with tricyclic antidepressants sometimes report nongastrointestinal symptoms; it is unclear whether these are drug side effects or reflect a behavioral tendency to report symptoms. We evaluated whether symptoms reported before treatment with a tricyclic antidepressant (desipramine) increased in number or worsened in severity after 2 weeks of treatment and assessed the baseline factors that predispose patients to report symptoms.

Methods: Female patients in a multicenter National Institutes of Health trial for functional bowel disorders completed a 15-item symptom questionnaire at baseline (before randomization), 2 weeks after they were given desipramine (n = 81) or placebo (n = 40), and at study completion (12 weeks).

The Toronto Bedside Swallowing Screening Test (TOR-BSST): development and validation of a dysphagia screening tool for patients with stroke.

Background And Purpose: Dysphagia occurs in 55% of all acute stroke patients. Early identification of dysphagia from screening can lead to earlier treatments and thereby reduce complications. We designed and validated a new bedside dysphagia screening tool-the Toronto Bedside Swallowing Screening Test (TOR-BSST) for stroke survivors in acute and rehabilitative settings.

Using different perspectives to generate items for a new scale measuring medical outcomes of dysphagia (MOD).

Objective: To compare and contrast clinician, patient, and caregiver perspectives to generate all important and salient items for a new scale to measure medical consequences relevant to adult patients with dysphagia.

Study Design And Setting: Six focus groups (three with clinicians, two with patients, and one with caregivers) were conducted with a total of 33 participants. Through the constant comparison method of Grounded Theory, analysis began with open coding and progressed with higher-order categorization to derive perceptions from differing vantage points.

Patient-centered measures for achalasia.

Background: Various instruments may be used to measure health-related quality of life in patients with achalasia.

Methods: We administered four patient-centered measures used for evaluation of achalasia severity [an achalasia severity questionnaire we developed previously, an achalasia symptom checklist, the Gastrointestinal Quality-of-Life Index (GIQLI), and the Medical Outcomes Study 36-item Short-Form survey (SF-36)] to 25 subjects enrolled in a randomized controlled trial comparing pneumatic dilatation and laparoscopic Heller myotomy. We estimated correlations between the different measures.

Survival dependency of intramuscular ICC on vagal afferent nerves in the cat esophagus.

Interstitial cells of Cajal (ICC) have been proposed as stretch receptors for vagal afferent nerves in the stomach based on immunohistochemical studies. The aim of the present study was to use electron microscopy and the anterograde degeneration technique to investigate ultrastructural features and survival dependency of ICC associated with vagal afferent innervation of the cat esophagus. This is the first report on the ultrastructural characteristics of ICC in the cat esophagus.

Characterization of health related quality of life (HRQOL) for patients with functional bowel disorder (FBD) and its response to treatment.

Background And Aims: Assessing health related quality of life (HRQOL) is becoming more important in research and clinical care. However, little information is available on the performance of HRQOL questionnaires for the functional bowel disorders (FBD). The aims of this study were to (a) understand the performance of the Sickness Impact Profile (SIP) and IBS-QOL for the functional bowel disorders at baseline and after treatment, (b) determine which HRQOL subscales best improve with treatment, (c) determine clinically meaningful improvement, and (d) determine the predictors of HRQOL at baseline and in response to treatment.

Modulation of the K(v)4.3 channel by syntaxin 1A.

The SNARE protein syntaxin 1A (Syn1A) is known to inhibit delayed rectifier K(+) channels of the K(v)1 and K(v)2 families with heterogeneous effects on their gating properties. In this study, we explored whether Syn1A could directly modulate K(v)4.3, a rapidly inactivating K(v) channel with important roles in neuroendocrine cells and cardiac myocytes.

Unique distribution of interstitial cells of Cajal in the feline pylorus.

The feline gastrointestinal (GI) tract is an important model for GI physiology but no immunohistochemical assessment of interstitial cells of Cajal (ICC) has been performed because of the lack of suitable antibodies. The aim of the present study was to investigate the various types of ICC and associated nerve structures in the pyloric sphincter region, by using immunohistochemistry and electron microscopy to complement functional studies. In the sphincter, ICC associated with Auerbach's plexus (ICC-AP) were markedly decreased within a region of 6-8 mm in length, thereby forming an interruption in this network of ICC-AP, which is otherwise continuous from corpus to distal ileum.

Distinct modulation of Kv1.2 channel gating by wild type, but not open form, of syntaxin-1A.

SNARE proteins, syntaxin-1A (Syn-1A) and SNAP-25, inhibit delayed rectifier K(+) channels, K(v)1.1 and K(v)2.1, in secretory cells.

Two populations of pancreatic islet alpha-cells displaying distinct Ca2+ channel properties.

In low or absence of glucose, alpha-cells generate rhythmic action potentials and secrete glucagon. alpha-Cell T-type Ca(2+) channels are believed to be pacemaker channels, which are expected to open near the resting membrane potential (around -60 mV) to initiate a small depolarization. A previous publication, however, showed that alpha-cell T-type Ca(2+) channels have an activation threshold of -40 mV, which does not appear to fulfill their role as pacemakers.

Insulin regulates islet alpha-cell function by reducing KATP channel sensitivity to adenosine 5'-triphosphate inhibition.

Glucose regulates pancreatic islet alpha-cell glucagon secretion directly by its metabolism to generate ATP in alpha-cells, and indirectly via stimulation of paracrine release of beta-cell secretory products, particularly insulin. How the cellular substrates of these pathways converge in the alpha-cell is not well known. We recently reported the use of the MIP-GFP (mouse insulin promoter-green fluorescent protein) mouse to reliably identify islet alpha- (non-green cells) and beta-cells (green cells), and characterized their ATP-sensitive K(+) (K(ATP)) channel properties, showing that alpha-cell K(ATP) channels exhibited a 5-fold higher sensitivity to ATP inhibition than beta-cell K(ATP) channels.

Dysphagia after stroke: incidence, diagnosis, and pulmonary complications.

Objective: To determine the incidence of dysphagia and associated pulmonary compromise in stroke patients through a systematic review of the published literature.

Methods: Databases were searched (1966 through May 2005) using terms "cerebrovascular disorders," "deglutition disorders," and limited to "humans" for original articles addressing the frequency of dysphagia or pneumonia. Data sources included Medline, Embase, Pascal, relevant Internet addresses, and extensive hand searching of bibliographies of identified articles.

Feline lower esophageal sphincter sling and circular muscles have different functional inhibitory neuronal responses.

The lower esophageal sphincter (LES) has a circular muscle component exhibiting spontaneous tone that is relaxed by nitric oxide (NO) and a low-tone sling muscle that contracts vigorously to cholinergic stimulation but with little or no evidence of NO responsiveness. This study dissected the responses of the sling muscle to nitrergic innervation in relationship to its cholinergic innervation and circular muscle responses. Motor responses were induced by electrical field stimulation (EFS; 1-30 Hz) of muscle strips from sling and circular regions of the feline LES in the presence of cholinergic receptor inhibition (atropine) or NO synthase inhibition [NG-nitro-L-arginine (L-NNA)+/-atropine].

A measure of disease-specific health-related quality of life for achalasia.

Objectives: To develop a measure of disease-specific health-related quality of life for achalasia for use as an outcome measure in clinical trials.

Methods: We generated a list of potential items for a measure of disease-specific health-related quality of life for achalasia by semistructured interviews with seven persons with achalasia, and by expert opinion. We then used factor analysis and item response theory methods for item reduction, using responses on the long-form questionnaire from 70 persons with achalasia.

Electrophysiological characterization of pancreatic islet cells in the mouse insulin promoter-green fluorescent protein mouse.

We recently reported a transgenic [mouse insulin promoter (MIP)-green fluorescent protein (GFP)] mouse in which GFP expression is targeted to the pancreatic islet beta-cells to enable convenient identification of beta-cells as green cells. The GFP-expressing beta-cells of the MIP-GFP mouse were functionally indistinguishable from beta-cells of normal mice. Here we characterized the ionic channel properties and exocytosis of MIP-GFP mouse islet beta- and alpha-cells.