Anxiety can significantly explain bolus perception in the context of hypotensive esophageal motility: Results of a large multicenter study in asymptomatic individuals.

BACKGROUND: Previous studies have not been able to correlate manometry findings with bolus perception. The aim of this study was to evaluate correlation of different variables, including traditional manometric variables (at diagnostic and extreme thresholds), esophageal shortening, bolus transit, automated impedance manometry (AIM) metrics and mood with bolus passage perception in a large cohort of asymptomatic individuals. METHODS: High resolution manometry (HRM) was performed in healthy individuals from nine centers. Perception was evaluated using a 5-point Likert scale. Anxiety was evaluated using Hospitalized Anxiety and Depression scale (HAD). Subgroup analysis was also performed classifying studies into normal, hypotensive, vigorous, and obstructive patterns. KEY RESULTS: One hundred fifteen studies were analyzed (69 using HRM and 46 using high resolution impedance manometry (HRIM); 3.5% swallows in 9.6% of volunteers were perceived. There was no correlation of any of the traditional HRM variables, esophageal shortening, AIM metrics nor bolus transit with perception scores. There was no HRM variable showing difference in perception when comparing normal vs extreme values (percentile 1 or 99). Anxiety but not depression was correlated with perception. Among hypotensive pattern, anxiety was a strong predictor of variance in perception (R2 up to .70). CONCLUSION AND INFERENCES: Bolus perception is less common than abnormal motility among healthy individuals. Neither esophageal motor function nor bolus dynamics evaluated with several techniques seems to explain differences in bolus perception. Different mechanisms seem to be relevant in different manometric patterns. Anxiety is a significant predictor of bolus perception in the context of hypotensive motility.

The Chicago Classification 3.0 Results in More Normal Findings and Fewer Hypotensive Findings With No Difference in Other Diagnoses.

OBJECTIVES: High-resolution manometry (HRM) is the preferred method for the evaluation of motility disorders. Recently, an update of the diagnostic criteria (Chicago 3.0) has been published. The aim of this study was to compare the performance criteria of Chicago version 2.0 (CC2.0) vs. 3.0 (CC3.0) in a cohort of healthy volunteers and symptomatic patients. METHODS: HRM studies of asymptomatic and symptomatic individuals from several centers of Spain and Latin America were analyzed using both CC2.0 and CC3.0. The final diagnosis was grouped into hierarchical categories: obstruction (achalasia and gastro-esophageal junction obstruction), major disorders (distal esophageal spasm, absent peristalsis, and jackhammer), minor disorders (failed frequent peristalsis, weak peristalsis with small or large defects, ineffective esophageal motility, fragmented peristalsis, rapid contractile with normal latency and hypertensive peristalsis) and normal. The results were compared using McNemar's and Kappa tests. RESULTS: HRM was analyzed in 107 healthy volunteers (53.3% female; 18-69 years) and 400 symptomatic patients (58.5% female; 18-90 years). In healthy volunteers, using CC2.0 and CC3.0, obstructive disorders were diagnosed in 7.5% and 5.6%, respectively, major disorders in 1% and 2.8%, respectively, minor disorders in 25.2% and 15%, respectively, and normal in 66.4% and 76.6%, respectively. In symptomatic individuals, using CC2.0 and CC3.0, obstructive disorders were diagnosed in 11% and 11.3%, respectively, major disorders in 14% and 14%, respectively, minor disorders in 33.3% and 24.5%, respectively, and normal in 41.8% and 50.3%, respectively. In both groups of individuals, only an increase in normal and a decrease in minor findings using CC3.0 were statistically significant using McNemar's test. DISCUSSIONS: CC3.0 increases the number of normal studies when compared with CC2.0, essentially at the expense of fewer minor disorders, with no significant differences in major or obstructive disorders. As the relevance of minor disorders is questionable, our data suggest that CC3.0 increases the relevance of abnormal results.

Normal values of esophageal pressure responses to a rapid drink challenge test in healthy subjects: results of a multicenter study.

BACKGROUND: Multiple water swallow is increasingly used as a complementary challenge test in patients undergoing high-resolution manometry (HRM). Our aim was to establish the range of normal pressure responses during the rapid drink challenge test in a large population of healthy subjects. METHODS: Pressure responses to a rapid drink challenge test (100 or 200 mL of water) were prospectively analyzed in 105 healthy subjects studied in nine different hospitals from different countries. Esophageal motility was assessed in all subjects by solid-state HRM. In 18 subjects, bolus transit was analyzed using concomitant intraluminal impedance monitoring. KEY RESULTS: A virtually complete inhibition of pressure activity was observed during multiple swallow: Esophageal body pressure was above 20 mm Hg during 1 (0-8) % and above 30 mm Hg during 1 (0-5) % of the swallow period, and the pressure gradient across the esophagogastric junction was low (-1 (-7 to 4) mm Hg). At the end of multiple swallow, a postswallow contraction was evidenced in only 50% of subjects, whereas the remaining 50% had non-transmitted contractions. Bolus clearance was completed after 7 (1-30) s after the last swallow, as evidenced by multichannel intraluminal impedance. CONCLUSIONS & INFERENCES: The range of normal pressure responses to a rapid drink challenge test in health has been established in a large multicenter study. Main responses are a virtually complete inhibition of esophageal pressures with a low-pressure gradient across esophagogastric junction. This data would allow the correct differentiation between normal and disease when using this test.

Modulation of M(2) muscarinic receptor-receptor interaction by immunoglobulin G antibodies from Chagas' disease patients.

Circulating immunoglobulin (Ig)G antibodies against M(2) muscarinic acetylcholine receptors (M(2) mAChR) have been implicated in Chagas' disease (ChD) pathophysiology. These antibodies bind to and activate their target receptor, displaying agonist-like activity through an unclear mechanism. This study tested the ability of serum anti-M(2) mAChR antibodies from chronic ChD patients to modulate M(2) muscarinic receptor-receptor interaction by bioluminescence resonance energy transfer (BRET). Human embryonic kidney (HEK) 293 cells co-expressing fusion proteins M(2) mAChR-Renilla luciferase (RLuc) and M(2) mAChR-yellow fluorescent protein (YFP) were exposed to the serum IgG fraction from ChD patients, and BRET between RLuc and YFP was assessed by luminometry. Unlike serum IgG from healthy subjects and conventional muscarinic ligands, ChD IgG promoted a time- and concentration-dependent increase in the BRET signal. This effect neither required cellular integrity nor occurred as a consequence of receptor activation. Enhancement of M(2) receptor-receptor interaction by ChD IgG was receptor subtype-specific and mediated by the recognition of the second extracellular loop of the M(2) mAChR. The monovalent Fab fragment derived from ChD IgG was unable to reproduce the effect of the native immunoglobulin. However, addition of ChD Fab in the presence of anti-human Fab IgG restored BRET-enhancing activity. These data suggest that the modulatory effect of ChD IgG on M(2) receptor-receptor interaction results from receptor cross-linking by bivalent antibodies.

Interaction of human chagasic IgG with human colon muscarinic acetylcholine receptor: molecular and functional evidence.

BACKGROUND AND AIMS: Gastrointestinal disorders is one of the clinical manifestations of chronic Chagas' disease. The pathogenesis seems to be associated with autonomic dysfunction. Here, we consider the muscarinic cholinoceptor mediated alteration in distal colon function in chagasic megacolon. PATIENTS: Patients were divided into four groups: group I, chronic chagasic patients with megacolon; group II, chronic chagasic patients without megacolon; group III, non-chagasic patients with megacolon; and group IV, normal healthy volunteers (control). METHODS: Binding assay and immunoblot of cholinoceptors from human and rat colon and enzyme immunoassay (ELISA) using a synthetic 24mer peptide corresponding to the second extracellular loop of human M2 muscarinic acetylcholine receptors (mAChR) were used to detect the presence of serum antibodies. The effect of antibodies on basal tone and 3',5'-cyclic monophosphate (cAMP) production of human and rat distal colon strips were also tested. RESULTS: Group I but not the other groups had circulating antibodies capable of interacting with human colon activating M2 mAChR, as they competed with binding of specific radioligand to mAChR and interacted with the second extracellular loop of human M2 mAChR. Moreover, affinity purified anti-M2 peptide IgG from group I, in common with monoclonal antihuman M2 mAChR, recognised bands with a molecular weight corresponding to colon mAChR. This antibody also displayed an agonist-like activity, increasing basal tone and decreasing cAMP accumulation. Both effects were blunted by AF-DX 116 and neutralised by the synthetic peptide. CONCLUSIONS: In chagasic patients with megacolon there are antibodies that can recognise and activate M2 mAChR. The implications of these autoantibodies in the pathogenesis of chagasic megacolon is discussed.

On the first-order Rao-Scott correction of the Umesh-Loughin-Scherer statistic.

Decady and Thomas (2000, Biometrics 56, 893-896) propose a first-order corrected Umesh-Loughin-Scherer statistic to test for association in an r x c contingency table with multiple column responses. Agresti and Liu (1999, Biometrics 55, 936-943) point out that such statistics are not invariant to the arbitrary designation of a zero or one to a positive response. This paper shows that, in addition, the proposed testing procedure does not hold the correct size when there are strong pairwise associations between responses.

Functional implications of circulating muscarinic cholinergic receptor autoantibodies in chagasic patients with achalasia.

BACKGROUND & AIMS: Autoantibodies against M(2)-muscarinic acetylcholine receptors (M(2) mAChR) have been reported in patients with chronic Chagas' disease who have cardiac dysautonomia. The aim of this study was to investigate the presence of such antibodies in chronic chagasic and non-chagasic patients with esophageal achalasia and their ability to activate M(2) mAChR in the isolated esophagus. METHODS: Enzyme-linked immunosorbent assay was used to detect serum immunoglobulin (Ig) G antibodies against a synthetic 24-mer peptide corresponding to the second extracellular loop of human M(2) mAChR. The effects of both total serum IgG and affinity-purified antipeptide antibodies on the contractile activity and adenosine 3', 5'-cyclic monophosphate (cAMP) production in rat esophageal strips were also tested. RESULTS: Circulating IgG antibodies from chagasic achalasia patients recognized the M(2)-peptide more often than those from non-chagasic achalasia patients (P < 0.0005) and normal subjects (P < 0.0001). A strong association between the existence of circulating anti-M(2) mAChR antibodies and the presence of achalasia in chagasic patients was found (P < 0.01). Both the total IgG fraction and anti-M(2)-peptide antibodies increased the basal tone, reduced the relaxant effect of isoproterenol, and decreased cAMP accumulation in esophageal strips, displaying a muscarinic agonist-like activity on M(2) mAChR. CONCLUSIONS: Patients with chronic Chagas' disease have circulating autoantibodies against M(2) mAChR. These antibodies could be involved in the pathophysiological mechanism of chagasic achalasia.

Colonic motility in man: features in normal subjects and in patients with chronic idiopathic constipation.

The human colon is still a relatively unknown viscus, especially concerning its motor activity. However, in recent years, techniques have been perfected that allow a better understanding of colonic motility, especially through prolonged recording periods. In this way, it has been demonstrated that the viscus contracts according to a circadian trend, is responsive to physiological stimuli (meals, sleep), and features high amplitude, propulsive contractions that are part of the complex dynamic of the defecatory process. These physiological properties and their alterations in patients with chronic idiopathic constipation are reviewed in this article.

Effect of bolus volume on the response of the human esophagus to a viscous bolus.

It is well known that increasing the volume of a non-viscous bolus has no significant effect on esophageal peristalsis. Viscous boluses, however, tend to remain more compact during passage through the esophagus; we therefore sought to determine whether increasing the volume of a viscous bolus would significantly affect esophageal peristalsis. Intraluminal pressure events were measured with a low-compliance-infused catheter system, and lower esophageal sphincter (LES) pressure was monitored continuously with a Dent sleeve. Each subject was given a series of 10 swallows of a water bolus (viscosity, 0.89 centipoise) and of a viscous bolus (syrup; viscosity, 102 centipoise). The volume of each bolus varied (5, 10, 15, 20 ml), and the order of administration of each set of swallows was randomized. Tracings were coded and analyzed blindly. Increasing the volume of the non-viscous bolus had no significant effects of esophageal peristalsis. Additionally, the viscous bolus at each volume was associated with significant (p less than 0.05) reductions in peristaltic wave velocity and significant (p less than 0.05) increments in durations of contraction and LES relaxation. However, increasing the volume of the viscous bolus did not significantly alter variables of esophageal peristalsis. It is concluded that altering the volume of a viscous bolus has no incremental effect on esophageal peristalsis over the effect of viscosity alone.

Effect of bolus osmolality on human esophageal function.

The effect of bolus osmolality on human esophageal function is undefined. We sought to define the response of the human esophagus to boluses with a wide range of osmolalities in 10 healthy male volunteers. Intraluminal pressure events were measured with an infused catheter system, and lower esophageal sphincter pressure was monitored continuously with a Dent sleeve. Each subject was given a series of 10 swallows of each of seven boluses, which consisted of water, mannitol solutions with osmolalities of 142, 296, 449, 704, and 1481 mOsm/kg, and orange juice (585 mOsm/kg), in a randomized fashion. Tracings were coded and analyzed blindly. Alterations in bolus osmolality did not elicit any significant changes in amplitude and duration of contraction, velocity of wave propagation, or the duration of relaxation of the lower esophageal sphincter. We conclude that bolus osmolality does not play a significant role in the control of human esophageal motility, and that this lack of effect is explained by consideration of esophageal muscle mechanics.

Abdomen agudo como forma de presentación de un adenoma hepático

Reportamos el caso de una mujer de 33 años que fue internada con un cuadro de abdomen agudo. Refería ingesta de anticonceptivos orales. Los hallazgos físicos fueron dolor abdominal, defensa y rigidez del cuadrante superior derecho. Se realizaron los seguientes estudios: los tests de laboratorio excluyeron hidatidosis y amebiasis. La ecografía mostró una imagen nodular en el lóbulo hepático derecho y una vía biliar normal. Con la tomográfia computada se observó una masa de baja densidad. Una biopsia con aguja guiada tomográficamente fue informada como hepatocitos normales. La angiografía mostró arterias hepáticas tortuosas. La laparoscopía reveló una formación sólida y se obtuvo sangre al punzarla. Se indicó una laparotimía. Se encontró un tumor en el lóbulo hepático derecho pero el cirujano no resecó la lelsión porque una biopsia por congelación no consiguió demostrar células tumorales. Se llegó l diagnóstico de adenoma hepático con la biopsia definitiva. Nuestra paciente tuvo buena evolución con la suspensión de los anticonceptivos y una tomografía demostró la remisión casi completa del tumor un año después de la cirugía. En 12-52% de los pacientes con un adenoma hepático se observó dolor como el síntoma inicial y comienzo brusco em 33% de ellos. Sin embargo no se considera frecuentemente este tumor como causa de abdomen agudo (AU)

Abdomen agudo como forma de presentación de un adenoma hepático

Reportamos el caso de una mujer de 33 años que fue internada con un cuadro de abdomen agudo. Refería ingesta de anticonceptivos orales. Los hallazgos físicos fueron dolor abdominal, defensa y rigidez del cuadrante superior derecho. Se realizaron los seguientes estudios: los tests de laboratorio excluyeron hidatidosis y amebiasis. La ecografía mostró una imagen nodular en el lóbulo hepático derecho y una vía biliar normal. Con la tomográfia computada se observó una masa de baja densidad. Una biopsia con aguja guiada tomográficamente fue informada como hepatocitos normales. La angiografía mostró arterias hepáticas tortuosas. La laparoscopía reveló una formación sólida y se obtuvo sangre al punzarla. Se indicó una laparotimía. Se encontró un tumor en el lóbulo hepático derecho pero el cirujano no resecó la lelsión porque una biopsia por congelación no consiguió demostrar células tumorales. Se llegó l diagnóstico de adenoma hepático con la biopsia definitiva. Nuestra paciente tuvo buena evolución con la suspensión de los anticonceptivos y una tomografía demostró la remisión casi completa del tumor un año después de la cirugía. En 12-52% de los pacientes con un adenoma hepático se observó dolor como el síntoma inicial y comienzo brusco em 33% de ellos. Sin embargo no se considera frecuentemente este tumor como causa de abdomen agudo

[Acute abdomen as form of presentation of hepatic adenoma]. / Abdomen agudo como forma de presentación de un adenoma hepático.

We report the case of a woman aged 33 years old who was admitted with an acute abdomen. She referred oral contraceptives intake. Physical findings were abdominal tenderness, involuntary guarding and right upper quadrant rigidity. The following studies were performed: laboratory tests excluded hydatidosis and amebiasis. Ultrasonography showed a nodular image in the right hepatic lobe and a normal biliary tract. A low-density mass was observed with the computed tomographic scanning. A tomographic guided needle biopsy was informed as normal liver cells. Angiography showed tortuous hepatic arteries. Laparoscopy revealed a solid formation blood was obtained when it was punctured. Laparotomy was indicated. A tumor in the right hepatic lobe was found but a surgeon did not resect the lesion because a congelation biopsy failed to demonstrate tumoral cells. The diagnosis of hepatic adenoma was reached with the definitive biopsy. Our patient had a good evolution with the contraceptives withdrawal and a tomographic scanning one year after surgery showed the almost complete remission of the tumor. Pain as the initial symptom was observed in 12-52% of patients with an hepatic adenoma an audden onset in 33% of them. However this tumor is not frequently considered as a cause of acute abdomen.

PIP: The case is described of a 33-year-old woman with an 8-year history of oral contraceptive (OC) use who was treated at a hospital in Buenos Aires for a hepatic adenoma. The woman was admitted with an acute abdomen. Apart from OC use she had a history of hypertension for which she was treated with clonidine and diuretics. The physical findings included pain in the right abdomen, involuntary guarding, vomiting, and fever. Ultrasonography showed a normal bladder and pancreas and a nodular image in the right hepatic lobe. A CAT scan revealed a mass in the right hepatic lobe, and a needle biopsy later showed normal hepatic cells. Laparoscopy revealed a solid formation from which blood was obtained on puncturing. Angiography showed tortuous hepatic arteries. Laboratory tests were normal. An exploratory laparotomy was performed when the different studies failed to establish a clear diagnosis. A tumor was found in the right hepatic lobe but was not respected because the frozen section biopsy did not show malignant cells. The definite diagnosis of hepatic adenoma was based on the definitive biopsy. OC treatment was terminated and the tumor was in almost complete remission 1 year later. Hepatic adenomas are benign tumors, usually single, which occur rarely and primarily in women aged 30-40 who use OCs. A review of the literature indicated that the forms of presentation of hepatic adenoma are very varied. Pain was the initial symptom in 12-52% of cases. The pain was of sudden onset in 1/3. Hepatic adenoma is however infrequently considered as a cause of acute abdomen. Treatment in 73% of cases is surgical because of the danger of hemorrhage and shock and because of the potential for malignant transformation.

Abdomen agudo como forma de presentación de un adenoma hepático. / [Acute abdomen as form of presentation of hepatic adenoma]

We report the case of a woman aged 33 years old who was admitted with an acute abdomen. She referred oral contraceptives intake. Physical findings were abdominal tenderness, involuntary guarding and right upper quadrant rigidity. The following studies were performed: laboratory tests excluded hydatidosis and amebiasis. Ultrasonography showed a nodular image in the right hepatic lobe and a normal biliary tract. A low-density mass was observed with the computed tomographic scanning. A tomographic guided needle biopsy was informed as normal liver cells. Angiography showed tortuous hepatic arteries. Laparoscopy revealed a solid formation blood was obtained when it was punctured. Laparotomy was indicated. A tumor in the right hepatic lobe was found but a surgeon did not resect the lesion because a congelation biopsy failed to demonstrate tumoral cells. The diagnosis of hepatic adenoma was reached with the definitive biopsy. Our patient had a good evolution with the contraceptives withdrawal and a tomographic scanning one year after surgery showed the almost complete remission of the tumor. Pain as the initial symptom was observed in 12-52

of patients with an hepatic adenoma an audden onset in 33

of them. However this tumor is not frequently considered as a cause of acute abdomen.

Esophageal motility in chagasic patients

Se estudió la motilidad esofágica en 16 individuos normales y 59 pacientes chagásicos crónicos. En éstos se realizaron estímulos con dosis submáximas de betanecol y pentagastrina con el objeto de estudiar si existe daño esofágico motor. Se obtuvieron los siguiéntes resultados: 1) no se encontraron diferencias en los trazados electromanométricos basales entre chagásicos y normales; 2) al utilizar estímulo colinérgico y hormonal, los trazados correspondientes a los pacientes chagásicos evidenciaron un significativo aumento de la presión de la zona de alta presión; 3) en los pacientes chagásicos se demostró un significativo incremento de la presión del cuerpo esofágico después del estímulo con betanecol y pentagastrina, así como un aumento en la duración de la onda peristáltica, y 4) no se detectaron alteraciones en los porcentajes de la velocidad de propagación de la onda peristáltica ni en la relajación cardial. Concluimos que en este grupo de pacientes chagásicos crónicos, procedentes de áreas endémicas argentinas, hallamos un comportamiento anormal de la motilidad esofágica sugestivo de daño neuronal precoz (AU)

Esophageal motility in chagasic patients

Se estudió la motilidad esofágica en 16 individuos normales y 59 pacientes chagásicos crónicos. En éstos se realizaron estímulos con dosis submáximas de betanecol y pentagastrina con el objeto de estudiar si existe daño esofágico motor. Se obtuvieron los siguiéntes resultados: 1) no se encontraron diferencias en los trazados electromanométricos basales entre chagásicos y normales; 2) al utilizar estímulo colinérgico y hormonal, los trazados correspondientes a los pacientes chagásicos evidenciaron un significativo aumento de la presión de la zona de alta presión; 3) en los pacientes chagásicos se demostró un significativo incremento de la presión del cuerpo esofágico después del estímulo con betanecol y pentagastrina, así como un aumento en la duración de la onda peristáltica, y 4) no se detectaron alteraciones en los porcentajes de la velocidad de propagación de la onda peristáltica ni en la relajación cardial. Concluimos que en este grupo de pacientes chagásicos crónicos, procedentes de áreas endémicas argentinas, hallamos un comportamiento anormal de la motilidad esofágica sugestivo de daño neuronal precoz