Evaluation of the sensitivity and specificity of basal plasma adrenocorticotrophic hormone concentration for diagnosing pituitary pars intermedia dysfunction in horses: A systematic review.

Measurement of basal adrenocorticotrophic hormone (ACTH) is currently used to diagnose pituitary pars intermedia dysfunction (PPID) in horses, yet a systematic review of the evidence for its use has not been undertaken. This study aimed to systematically review evidence regarding the sensitivity and specificity of the basal ACTH diagnostic test. Electronic databases were systematically searched in January 2019, September 2020 and January 2021, for English language publications published prior to these dates. Screening, data extraction and quality assessment of publications was undertaken by the authors using predefined criteria. Study design, methodology and information reported in included studies were assessed using Standards for Reporting of Diagnostic Accuracy (STARD) checklists. Risk of bias and applicability were appraised using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2) quality assessment tool. Due to identified biases and marked between-study variations, meta-analysis was not undertaken. After removal of duplicates, 415 publications were identified, of which 25 were evaluated in full, with 11 of these meeting inclusion criteria. In most studies, basal ACTH was reported to have good sensitivity (overall median 75.5%; interquartile range [IQR], 64.0-86.5%; range, 36.0-100%) and excellent specificity (overall median, 95.2%; IQR, 84.2-98.9%; range, 63.3-100%). However, QUADAS-2 and STARD assessment highlighted that studies did not utilise optimal study design and/or study populations for the evaluation of a diagnostic test and the majority were subject to bias, or provided insufficient information to fully assess possible biases. Based on this review, basal ACTH performed better at ruling out PPID than detecting it.

Microevolution in the pansecondary metabolome of Aspergillus flavus and its potential macroevolutionary implications for filamentous fungi.

Fungi produce a wealth of pharmacologically bioactive secondary metabolites (SMs) from biosynthetic gene clusters (BGCs). It is common practice for drug discovery efforts to treat species' secondary metabolomes as being well represented by a single or a small number of representative genomes. However, this approach misses the possibility that intraspecific population dynamics, such as adaptation to environmental conditions or local microbiomes, may harbor novel BGCs that contribute to the overall niche breadth of species. Using 94 isolates of Aspergillus flavus, a cosmopolitan model fungus, sampled from seven states in the United States, we dereplicate 7,821 BGCs into 92 unique BGCs. We find that more than 25% of pangenomic BGCs show population-specific patterns of presence/absence or protein divergence. Population-specific BGCs make up most of the accessory-genome BGCs, suggesting that different ecological forces that maintain accessory genomes may be partially mediated by population-specific differences in secondary metabolism. We use ultra-high-performance high-resolution mass spectrometry to confirm that these genetic differences in BGCs also result in chemotypic differences in SM production in different populations, which could mediate ecological interactions and be acted on by selection. Thus, our results suggest a paradigm shift that previously unrealized population-level reservoirs of SM diversity may be of significant evolutionary, ecological, and pharmacological importance. Last, we find that several population-specific BGCs from A. flavus are present in Aspergillus parasiticus and Aspergillus minisclerotigenes and discuss how the microevolutionary patterns we uncover inform macroevolutionary inferences and help to align fungal secondary metabolism with existing evolutionary theory.

Efficacy of pergolide for the management of equine pituitary pars intermedia dysfunction: A systematic review.

Pergolide, a dopamine agonist, is commonly administered to manage pituitary pars intermedia dysfunction (PPID), a progressive neurodegenerative disease prevalent in aged horses. However, available evidence regarding pergolide's efficacy in improving clinical and endocrine parameters is limited. The aim of this systematic review was to assess published literature and evaluate evidence regarding whether pergolide treatment results in improvement of clinical signs and/or adrenocorticotrophic hormone (ACTH) concentration compared to no treatment or other unlicensed treatments. Systematic searches of electronic databases were undertaken in April 2019, repeated in August and October 2019, and updated in July 2020. English language publications published prior to these dates were included. Screening, data extraction and quality assessment of publications was undertaken individually by the authors using predefined criteria and subsequently cross-checked. Modified critically appraised topic data collection forms were used to extract data. Due to marked between-study variations, meta-analysis was not undertaken. After removal of duplicate records; 612 publications were identified, of which 129 abstracts were screened for eligibility and 28 publications met criteria for inclusion in the review. Most studies were descriptive case series, cohort studies or non-randomised, uncontrolled field trials. Despite marked variation in study populations, case selection, diagnostic protocols, pergolide dose, follow-up period and outcome measures, in the vast majority of the included studies, pergolide was reported to provide overall clinical improvement in >75% of cases. However, reported improvements in individual clinical signs varied widely. A reduction in plasma ACTH concentrations was reported in 44-74% of cases, while normalisation to within reported reference intervals occurred in 28-74% of cases.

The Frequency of Sex: Population Genomics Reveals Differences in Recombination and Population Structure of the Aflatoxin-Producing Fungus Aspergillus flavus.

The apparent rarity of sex in many fungal species has raised questions about how much sex is needed to purge deleterious mutations and how differences in frequency of sex impact fungal evolution. We sought to determine how differences in the extent of recombination between populations of Aspergillus flavus impact the evolution of genes associated with the synthesis of aflatoxin, a notoriously potent carcinogen. We sequenced the genomes of, and quantified aflatoxin production in, 94 isolates of A. flavus sampled from seven states in eastern and central latitudinal transects of the United States. The overall population is subdivided into three genetically differentiated populations (A, B, and C) that differ greatly in their extent of recombination, diversity, and aflatoxin-producing ability. Estimates of the number of recombination events and linkage disequilibrium decay suggest relatively frequent sex only in population A. Population B is sympatric with population A but produces significantly less aflatoxin and is the only population where the inability of nonaflatoxigenic isolates to produce aflatoxin was explained by multiple gene deletions. Population expansion evident in population B suggests a recent introduction or range expansion. Population C is largely nonaflatoxigenic and restricted mainly to northern sampling locations through restricted migration and/or selection. Despite differences in the number and type of mutations in the aflatoxin gene cluster, codon optimization and site frequency differences in synonymous and nonsynonymous mutations suggest that low levels of recombination in some A. flavus populations are sufficient to purge deleterious mutations.IMPORTANCE Differences in the relative frequencies of sexual and asexual reproduction have profound implications for the accumulation of deleterious mutations (Muller's ratchet), but little is known about how these differences impact the evolution of ecologically important phenotypes. Aspergillus flavus is the main producer of aflatoxin, a notoriously potent carcinogen that often contaminates food. We investigated if differences in the levels of production of aflatoxin by A. flavus could be explained by the accumulation of deleterious mutations due to a lack of recombination. Despite differences in the extent of recombination, variation in aflatoxin production is better explained by the demography and history of specific populations and may suggest important differences in the ecological roles of aflatoxin among populations. Furthermore, the association of aflatoxin production and populations provides a means of predicting the risk of aflatoxin contamination by determining the frequencies of isolates from low- and high-production populations.

The 2018 ISDE achalasia guidelines.

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

Translocation of the papillomavirus L2/vDNA complex across the limiting membrane requires the onset of mitosis.

The human papillomavirus type 16 (HPV16) L2 protein acts as a chaperone to ensure that the viral genome (vDNA) traffics from endosomes to the trans-Golgi network (TGN) and eventually the nucleus, where HPV replication occurs. En route to the nucleus, the L2/vDNA complex must translocate across limiting intracellular membranes. The details of this critical process remain poorly characterized. We have developed a system based on subcellular compartmentalization of the enzyme BirA and its cognate substrate to detect membrane translocation of L2-BirA from incoming virions. We find that L2 translocation requires transport to the TGN and is strictly dependent on entry into mitosis, coinciding with mitotic entry in synchronized cells. Cell cycle arrest causes retention of L2/vDNA at the TGN; only release and progression past G2/M enables translocation across the limiting membrane and subsequent infection. Microscopy of EdU-labeled vDNA reveals a rapid and dramatic shift in vDNA localization during early mitosis. At late G2/early prophase vDNA egresses from the TGN to a pericentriolar location, accumulating there through prometaphase where it begins to associate with condensed chromosomes. By metaphase and throughout anaphase the vDNA is seen bound to the mitotic chromosomes, ensuring distribution into both daughter nuclei. Mutations in a newly defined chromatin binding region of L2 potently blocked translocation, suggesting that translocation is dependent on chromatin binding during prometaphase. This represents the first time a virus has been shown to functionally couple the penetration of limiting membranes to cellular mitosis, explaining in part the tropism of HPV for mitotic basal keratinocytes.

Classification of esophageal motor findings in gastro-esophageal reflux disease: Conclusions from an international consensus group.

BACKGROUND: High-resolution manometry (HRM) has resulted in new revelations regarding the pathophysiology of gastro-esophageal reflux disease (GERD). The impact of new HRM motor paradigms on reflux burden needs further definition, leading to a modern approach to motor testing in GERD. METHODS: Focused literature searches were conducted, evaluating pathophysiology of GERD with emphasis on HRM. The results were discussed with an international group of experts to develop a consensus on the role of HRM in GERD. A proposed classification system for esophageal motor abnormalities associated with GERD was generated. KEY RESULTS: Physiologic gastro-esophageal reflux is inherent in all humans, resulting from transient lower esophageal sphincter (LES) relaxations that allow venting of gastric air in the form of a belch. In pathological gastro-esophageal reflux, transient LES relaxations are accompanied by reflux of gastric contents. Structural disruption of the esophagogastric junction (EGJ) barrier, and incomplete clearance of the refluxate can contribute to abnormally high esophageal reflux burden that defines GERD. Esophageal HRM localizes the LES for pH and pH-impedance probe placement, and assesses esophageal body peristaltic performance prior to invasive antireflux therapies and antireflux surgery. Furthermore, HRM can assess EGJ and esophageal body mechanisms contributing to reflux, and exclude conditions that mimic GERD. CONCLUSIONS & INFERENCES: Structural and motor EGJ and esophageal processes contribute to the pathophysiology of GERD. A classification scheme is proposed incorporating EGJ and esophageal motor findings, and contraction reserve on provocative tests during HRM.

Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: Update of the Porto consensus and recommendations from an international consensus group.

BACKGROUND: An international group of experts evaluated and revised recommendations for ambulatory reflux monitoring for the diagnosis of gastro-esophageal reflux disease (GERD). METHODS: Literature search was focused on indications and technical recommendations for GERD testing and phenotypes definitions. Statements were proposed and discussed during several structured meetings. KEY RESULTS: Reflux testing should be performed after cessation of acid suppressive medication in patients with a low likelihood of GERD. In this setting, testing can be either catheter-based or wireless pH-monitoring or pH-impedance monitoring. In patients with a high probability of GERD (esophagitis grade C and D, histology proven Barrett's mucosa >1 cm, peptic stricture, previous positive pH monitoring) and persistent symptoms, pH-impedance monitoring should be performed on treatment. Recommendations are provided for data acquisition and analysis. Esophageal acid exposure is considered as pathological if acid exposure time (AET) is greater than 6% on pH testing. Number of reflux episodes and baseline impedance are exploratory metrics that may complement AET. Positive symptom reflux association is defined as symptom index (SI) >50% or symptom association probability (SAP) >95%. A positive symptom-reflux association in the absence of pathological AET defines hypersensitivity to reflux. CONCLUSIONS AND INFERENCES: The consensus group determined that grade C or D esophagitis, peptic stricture, histology proven Barrett's mucosa >1 cm, and esophageal acid exposure greater >6% are sufficient to define pathological GERD. Further testing should be considered when none of these criteria are fulfilled.

Benchmarks for the interpretation of esophageal high-resolution manometry.

BACKGROUND: Competent interpretation of esophageal high-resolution manometry (HRM) is integral to a quality study. Currently, methods to assess physician competency for the interpretation of esophageal HRM do not exist. The aim of this study was to use formal techniques to (i) develop an HRM interpretation exam, and (ii) establish minimum competence benchmarks for HRM interpretation skills at the trainee, physician interpreter, and master level. METHODS: A total of 29 physicians from 8 academic centers participated in the study: 9 content experts separated into 2 study groups-expert test-takers (n=7) and judges (n=2), and 20 HRM inexperienced trainees ("trainee test-taker"; n=20). We designed the HRM interpretation exam based on expert consensus. Expert and trainee test-takers (n=27) completed the exam. According to the modified Angoff method, the judges reviewed the test-taker performance and established minimum competency cut scores for HRM interpretation skills. KEY RESULTS: The HRM interpretation exam consists of 22 HRM cases with 8 HRM interpretation skills per case: identification of pressure inversion point, hiatal hernia >3 cm, integrated relaxation pressure, distal contractile integral, distal latency, peristaltic integrity, pressurization pattern, and diagnosis. Based on the modified Angoff method, minimum cut scores for HRM interpretation skills at the trainee, physician interpreter, and master level ranged from 65-80%, 85-90% (with the exception of peristaltic integrity), and 90-95%, respectively. CONCLUSIONS & INFERENCES: Using a formal standard setting technique, we established minimum cut scores for eight HRM interpretation skills across interpreter levels. This examination and associated cut scores can be applied in clinical practice to judge competency.

Esophageal hypermotility: cause or effect?

Nutcracker esophagus (NE), Jackhammer esophagus (JHE), distal esophageal spasm (DES), and hypertensive lower esophageal sphincter (HTLES) are defined by esophageal manometric findings. Some patients with these esophageal motility disorders also have abnormal gastroesophageal reflux. It is unclear to what extent these patients' symptoms are caused by the motility disorder, the acid reflux, or both. The aim of this study was to determine the effectiveness of laparoscopic Nissen fundoplication (LNF) on esophageal motility disorders, gastroesophageal reflux, and patient symptoms. Between 2007 and 2013, we performed high-resolution esophageal manometry on 3400 patients, and 221 patients were found to have a spastic esophageal motility disorder. The medical records of these patients were reviewed to determine the manometric abnormality, presence of gastroesophageal symptoms, and amount of esophageal acid exposure. In those patients that underwent LNF, we compared pre- and postoperative esophageal motility, gastroesophageal symptom severity, and esophageal acid exposure. Of the 221 patients with spastic motility disorders, 77 had NE, 2 had JHE, 30 had DES, and 112 had HTLES. The most frequently reported primary and secondary symptoms among all patients were: heartburn and/or regurgitation, 69.2%; respiratory, 39.8%; dysphagia, 35.7%; and chest pain, 22.6%. Of the 221 patients, 192 underwent 24-hour pH monitoring, and 103 demonstrated abnormal distal esophageal acid exposure. Abnormal 24-hour pH monitoring was detected in 62% of patients with heartburn and regurgitation, 49% of patients with respiratory symptoms, 36.8 % of patients with dysphagia, and 32.6% of patients with chest pain. Sixty-six of the 103 patients with abnormal 24-hour pH monitoring underwent LNF. Thirty-eight (13NE, 2JHE, 6 DES, and 17 HTLES) of these 66 patients had a minimum of 6-month postoperative follow-up that included clinical evaluation, esophageal manometry, and 24-hour pH monitoring. Postoperatively, all 38 patients had normal distal esophageal acid exposure. Of these 38 patients, symptoms resolved in 28 and improved in 10. Of six patients (one with NE, two JHE, and three with HTLES) that underwent postoperative esophageal manometry, five exhibited normal motility. Typical reflux symptoms are common among patients with esophageal hypermotility disorders. Abnormal 24-hour pH monitoring is present in the majority of patients with who report typical reflux symptoms and almost half of patients who report respiratory symptoms. Conversely, the majority of patients who report dysphagia or chest pain have normal distal esophageal acid exposure. Based on a small number of patients in this study, it also appears that motility disorders often improve after LNF. LNF is associated with resolution or improvement in reflux related symptoms and esophageal motility parameters in patients exhibiting abnormal esophageal acid exposure. This suggests that patient symptoms are due to abnormal acid exposure and not the motility disorder.

Prevalence of respiratory symptoms in patients with achalasia.

Achalasia is a primary esophageal motor disorder that results in poor clearance of the esophagus. Although an esophagus filled with debris and undigested food should put these patients at risk for aspiration, the frequency with which the latter occurs has never been documented. In this study, we sought to determine the incidence of respiratory symptoms and complaints in patients with achalasia. A comprehensive symptom questionnaire was administered to 110 patients with achalasia presenting to the Swallowing Center at the University of Washington between 1994 and 2008 as part of their preoperative work-up. Questionnaires were analyzed for the frequency of respiratory complaints in addition to the more typical symptoms of dysphagia, regurgitation, and chest pain. Twenty-two achalasia patients with respiratory symptoms who had also undergone Heller myotomy and completed a post-op follow-up questionnaire were analyzed as a subset. Ninety-five patients (86%) complained of at least daily dysphagia. Fifty-one patients (40%) reported the occurrence of at least one respiratory symptom daily, including cough in 41 patients (37%), aspiration (the sensation of inhaling regurgitated esophagogastric material) in 34 patients (31%), hoarseness in 23 patients (21%), wheezing in 17 patients (15%), shortness of breath in 11 patients (10%), and sore throat in 13 patients (12%). Neither age nor gender differed between those with and those without respiratory symptoms. In the subset of patients with respiratory symptoms who had undergone Heller myotomy, respiratory symptoms improved in the majority after the procedure. Patients with achalasia experience respiratory symptoms with much greater frequency than the approximately 10% that was previously believed. Awareness of this association may be important in the workup and ultimate treatment of patients with this uncommon esophageal disorder.

Does combined multichannel intraluminal esophageal impedance and manometry predict postoperative dysphagia after laparoscopic Nissen fundoplication?

Laparoscopic Nissen fundoplication (LNF) is an effective treatment for gastroesophageal reflux disease; however, some patients develop dysphagia postoperatively. Manometry is used to evaluate disorders of peristalsis, but has not been proven useful to identify which patients may be at risk for postoperative dysphagia. Multichannel intraluminal impedance (MII) evaluates the effective clearance of a swallowed bolus through the esophagus. We hypothesized that MII combined with manometry may detect those patients most at risk of developing dysphagia after LNF. Between March 2003 and January 2007, 74 patients who agreed to participate in this study were prospectively enrolled. All patients completed a preoperative symptom questionnaire, MII/manometry, and 24-h pH monitoring. All patients underwent LNF. Symptom questionnaires were administered postoperatively at a median of 18 months (range: 6-46 months), and we defined dysphagia (both preoperatively and postoperatively) as occurring more than once a month with a severity >or=4 (0-10 Symptom Severity Index). Thirty-two patients (43%) reported preoperative dysphagia, but there was no significant difference in pH monitoring, lower esophageal sphincter pressure/relaxation, peristalsis, liquid or viscous bolus transit (MII), or bolus transit time (MII) between patients with and without preoperative dysphagia. In those patients reporting preoperative dysphagia, the severity of dysphagia improved significantly from 6.8 +/- 2 to 2.6 +/- 3.4 (P < 0.001) after LNF. Thirteen (17%) patients reported dysphagia postoperatively, 10 of whom (75%) reported some degree of preoperative dysphagia. The presence of postoperative dysphagia was significantly more common in patients with preoperative dysphagia (P= 0.01). Patients with postoperative dysphagia had similar lower esophageal sphincter pressure and relaxation, peristalsis, and esophageal clearance to those without dysphagia. Neither MII nor manometry predicts dysphagia in patients with gastroesophageal reflux disease or its occurrence after LNF. The presence of dysphagia preoperatively is the only predictor of dysphagia after LNF.

Reduced tLESR elicitation in response to gastric distension in fundoplication patients.

Transient lower esophageal sphincter relaxations (tLESRs) are vagally mediated in response to gastric cardiac distension. Nine volunteers, eight gastroesophageal reflux disease (GERD) patients, and eight fundoplication patients were studied. Manometry with an assembly that included a barostat bag was done for 1 h with and 1 h without barostat distension to 8 mmHg. Recordings were scored for tLESRs and barostat bag volume. Fundoplication patients had fewer tLESRs (0.4 +/- 0.3/h) than either normal subjects (2.4 +/- 0.5/h) or GERD patients (2.0 +/- 0.3/h). The tLESRs rate increased significantly in normal subjects (5.8 +/- 0.9/h) and GERD patients (5.4 +/- 0.8/h) during distension but not in the fundoplication group. All groups exhibited similar gastric accommodation (change in volume/change in pressure) in response to distension. Fundoplication patients exhibit a lower tLESR rate at rest and a marked attenuation of the response to gastric distension compared with either controls or GERD patients. Gastric accommodation was not impaired with fundoplication. This suggests that the receptive field for triggering tLESRs is contained within a wider field for elicitation of gastric receptive relaxation and that only the first is affected by fundoplication.

Manometric heterogeneity in patients with idiopathic achalasia.

BACKGROUND & AIMS: In certain cases of achalasia, particularly those in early stages with minimal endoscopic or radiographic abnormalities, the diagnosis may rely on manometry, which is the most sensitive test for the disease. The aim of this study was to critically evaluate the manometric criteria in a population of patients with idiopathic achalasia. METHODS: Clinical histories and manometric recordings of 58 patients with idiopathic achalasia and 43 control subjects were analyzed with regard to esophageal body contraction amplitude, peristaltic effectiveness in terms of both completeness and propagation velocity, lower esophageal sphincter (LES) resting pressure, LES relaxation pressure, and intraesophageal-intragastric pressure gradient. Variants of achalasia were defined by finding manometric features that significantly differed from the remainder of achalasia patients, such that the diagnosis might be questioned. RESULTS: Four manometrically distinct variants were identified. These variants were characterized by (1) the presence of high amplitude esophageal body contractions, (2) a short segment of esophageal body aperistalsis, (3) retained complete deglutitive LES relaxation, and (4) intact transient LES relaxation. In each instance, the most extreme variant is discussed and compared with the remainder of the achalasia population and with controls. CONCLUSIONS: The significance in defining these variants of achalasia lies in the recognition that these sometimes confusing manometric findings are consistent with achalasia when combined with additional clinical data supportive of the diagnosis. Furthermore, such variants provide important clues into the pathophysiology of this rare disorder.

Osteochondritis dissecans of the knee: a radiology case report.

OBJECTIVE: To discuss the case of a patient with osteochondritis dissecans, a common disorder primarily affecting children and adolescent patients that involves the medial femoral condyle, and to examine its radiologic appearance. CLINICAL FEATURES: A 25-year-old man with knee pain sought treatment at a chiropractic clinic. The patient had a 2-year history of left knee pain that was exacerbated by activity and relieved with rest. Plain film radiography of the knee revealed findings consistent with osteochondritis dessicans. INTERVENTION AND OUTCOME: The patient was promptly referred for a concurrent orthopedic consultation with subsequent management. A trial basis of conservative care was initiated with the possibility of future surgical intervention if necessary. CONCLUSIONS: Osteochondritis dissecans is a common disorder of unknown and perhaps controversial cause. The disease is characterized by a fragment of articular cartilage and subchondral bone (osteochondral fragment) that becomes separated from the underlying bone. Treatment is aimed primarily at the preservation of articular surface congruity.

Bolus transit assessed by an esophageal stress test in postfundoplication dysphagia.

INTRODUCTION: Dysphagia is common after Nissen fundoplication but the relationship between dysphagia and bolus transit is poorly defined. This study compared bolus transit of fundoplication patients to normal individuals. METHODS: Twelve fundoplication patients and 20 healthy volunteers rated their ability to swallow eight bolus consistencies from no difficulty (0) to extreme difficulty (3) to compute a dysphagia score (range = 0-24). A 16-lumen manometric assembly was positioned across the esophagogastric junction (EGJ) and subjects were imaged fluoroscopically in a supine posture while swallowing 5 cc liquid barium and a 5-cc marshmallow-like viscoelastic barium bolus. Videofluoroscopic images were analyzed for total esophageal transit time and the fraction of time required to cross the EGJ. Manometric tracings were analyzed for the intrabolus pressure proximal to the EGJ, intragastric pressure, and distal peristaltic amplitude for each bolus. RESULTS: Dysphagia scores for fundoplication patients were significantly higher (7.3 +/- 5.1, range = 1-17) than for normals (0.5 +/- 0.6, range = 0-2). This correlated with longer total transit times for liquids and solids (r = 0.60, P < 0.01) and a greater percentage of transit time attributable to the EGJ transit. Retrograde flow at the EGJ (escape of bolus proximally up the esophagus) and peristaltic dysfunction were more frequent in fundoplication patients. However, no differences existed in manometric parameters between groups. CONCLUSIONS: Fundoplication impairs both liquid and solid esophageal bolus transit. Dysphagia perceived by fundoplication patients correlated with increased transit time, particularly across the EGJ. Combined quantitative evaluation with manometry and fluoroscopy reveals functional defects in fundoplication subjects, which are not evident by either modality alone.

Operative manometry and endoscopy during laparoscopic Heller myotomy. An initial experience.

BACKGROUND: We report our initial experience using operative esophageal manometry as an adjunct to endoscopy to determine the completeness of esophagogastric high-pressure zone (HPZ) obliteration during laparoscopic Heller myotomy. METHODS: Between July 1997 and October 1998, we performed laparoscopic Heller myotomies in 20 patients (eight male, 12 female; median age, 41 years). Mean duration of symptoms was 3.2 +/- 2.6 years (r = 0.5-11), and 45% of the patients had received prior dilation or toxin injection. A 16-channel esophageal manometry catheter was placed prior to anesthesia, with sites crossing the lower esophageal sphincter (LES). An endoscope was passed intraoperatively to localize the squamocolumnar junction, and the myotomy was performed. While the translucency was imaged in the area of the incision, we determined the adequacy of myotomy by visual assessment of LES and gastric cardia opening in response to endoscopic air insufflation. Manometry was then performed to detect any potential residual high pressure at the myotomized esophagogastric junction (EGJ). If it was found, the locus of persistent pressure was identified by probing along the myotomy, and residual muscle fibers were cut to yield a minimum pressure at the EGJ. RESULTS: A persistent HPZ was identified after the initial myotomy in 10 of 20 patients (50%). A Dor fundoplasty completed the operation. The mean operating time was 2.6 +/- 0.5 h (median, 2.5; r = 2-3.5 h), and the mean hospital stay was 1.6 +/- 1 days (median, 1, r = 1-5 days). The mean LES pressure was 2 +/- 3 mmHg immediately postmyotomy (p < 0.001 compared with preoperative value). Of 20 patients, only two have reported recurrence of dysphagia (10%). One had a recurrent HPZ on manometry, and one developed esophagitis, which resolved with omeprazole. CONCLUSIONS: Our initial experience suggests that operative esophageal manometry is a useful adjunct to upper endoscopy during laparoscopic Heller myotomy, quantitatively assuring obliteration of the nonrelaxing LES and HPZ.

Esophageal solid bolus transit: studies using concurrent videofluoroscopy and manometry.

OBJECTIVE: Our aim was to assess the efficacy and mechanism of solid bolus transit through the esophagus. METHODS: Eight healthy volunteers were studied with concurrent manometry and videofluoroscopy while swallowing 5 ml liquid barium, a 5-6 mm diameter bread ball, and 4 g chewed bread in both a supine and upright posture. As many as four successive swallows were performed until clearance was achieved. RESULTS: The esophageal clearance of liquid barium was 100% with the first swallow. Clearance of the unchewed bread ball occurred with the first swallow in only 6.7% of trials in the upright posture and 5.9% in the supine posture. After four swallows, clearance was 100% and 52.9% in the upright and supine postures, respectively. Chewed bread was more readily cleared than unchewed bread, with 100% clearance after two swallows in the upright posture and 91% clearance after four swallows in the supine posture. The most common locus of bread stasis was at the aortic arch and carina. The bread boluses were noted to move more effectively when localized in the head as opposed to the tail of the bolus composite. Nonocclusive contractions often occurred at the bolus tail despite the increased peristaltic amplitude seen with the chewed bread. Failed peristalsis, a frequent cause for solid clearance failure, was observed during 30% of all bread swallows. This usually occurred distal to the stopping point of the bolus, suggesting it to be the result rather than the cause of impaired transit. CONCLUSIONS: Although infrequently perceived by these normal subjects and in contradistinction to liquid clearance, bread is rarely cleared from the esophagus with a single swallow. Mastication and an upright posture facilitate the esophageal transport of solids. Bolus composition and impaired bolus transit alter the amplitude and conductance of peristalsis. Manometric data pertaining to liquid clearance through the esophagus do not readily apply to bread.

Esophageal sensitivity and symptom perception in gastroesophageal reflux disease.

Patients with gastroesophageal reflux disease (GERD) experience a wide spectrum of symptoms, varying both in quality and severity. This review summarizes clinical observations of esophageal sensitivity and symptom perception in GERD patients. The Bernstein test, although lacking standardization, remains a useful tool in determining esophageal sensitivity to acid stimuli. Ambulatory 24-hour pH monitoring with symptom event marking and subsequent symptom-reflux correlation between acid reflux events and esophageal symptomatology now provides an alternative method for establishing esophageal acid sensitivity. The intraesophageal balloon distention test (IEBD) was developed to assess esophageal sensitivity to mechanical stimuli. Variants of each of these tests have been applied to the evaluation of uncomplicated GERD patients and patients with esophagitis and Barrett's metaplasia, who generally demonstrate less esophageal sensitivity than the former group. Studies using these methods have demonstrated increased esophageal sensitivity in patients with esophageal chest pain and have also identified a subset of patients with esophageal symptoms yet normal esophageal acid exposure, a condition referred to as "hypersensitive esophagus." The Bernstein test, 24-hour pH monitoring with symptom assessment, and IEBD have each contributed to our understanding of esophageal pain syndromes; it is hoped that future work in this area will lead to improved and more specific therapy for these patients.

Two new schemes for classifying propagating cracks in human tooth structure.

Currently, the dental profession has no comprehensive classification method or scheme to identify the many types of propagating cracks in human tooth structure. This article presents two new and practical classification systems that encompass numerous types of cracks. The first is the more simplified--the Surface and Position Classification System. The second and more comprehensive system is the Directional Crack Propagation System.