Prolonged manometric recordings of oesophagus and lower oesophageal sphincter in achalasia patients

BACKGROUND AND AIMS: Conventional short term manometry is a valuable tool in the diagnosis of achalasia but the technique may fail to detect intermittent motor events. The aim of this study was to investigate the pattern of lower oesophageal sphincter (LOS) and oesophageal pressures during prolonged recording in patients with achalasia. METHODS: Eleven patients with idiopathic achalasia were studied. Prolonged combined oesophageal pH and manometric recordings of the pharynx, LOS, and stomach were performed using a pH glass electrode and a multiple lumen assembly incorporating a Dent sleeve connected to a portable water perfused manometric system. RESULTS: LOS pressure varied during the day. Postprandial LOS pressures were lower than those recorded preprandially (1.2 v 1.8 kPa; p=0.005) and basal LOS pressures were significantly higher during phase III of the migrating motor complex than during the subsequent phase I (3.3 v 1.8 kPa; p=0.028). Complete LOS relaxations were occasionally observed in seven patients (0.48/h). Complete LOS relaxations were longer in duration than incomplete LOS relaxations (10.8 v 2.8 s; p=0.01) and 57% of complete relaxations fulfilled the criteria of a transient LOS relaxation (TLOSR). Complete LOS relaxations were associated with oesophageal pressure waves with higher amplitudes and longer durations. In addition, a higher proportion of these oesophageal pressure waves were spontaneous (55.6% v 0%; p<0.02) and multipeaked (72.7% v 0%). During prolonged manometry, high amplitude oesophageal pressure waves (>10 kPa) were recorded in six patients and retrograde oesophageal pressure waves in four, phenomena which were not observed during short term manometry. CONCLUSION: In contrast with short term stationary manometry, prolonged manometry in achalasia patients revealed the occurrence of complete LOS relaxations, TLOSRs, variations in LOS pressure associated with a meal or phase III, and high amplitude and retrograde oesophageal pressure waves.     

Zellweger syndrome in a preterm,small for gestational age infant

Summary A preterm (gestational age 34 weeks), small for gestational age infant (birth weight <P _2,3) is described. Because of unexplained slightly disturbed liver function tests at age 2 months, extensive metabolic examinations were performed. Elevated blood levels of very long-chain fatty acids, pipecolic acid and abnormal levels of bile acid intermediates were detected, suggesting a peroxisomal disorder. The plasmalogen content of erythrocytes was decreased. Morphologically distinct peroxisomes were absent in the liver. In fibroblasts an accumulation of very long-chain fatty acids, decreased activity of acyl-CoA: dihydroxyacetone phosphate acyltransferase and impairedde novo biosynthesis of plasmalogens was found.In summary, a mild variant of the classical cerebro-hepato-renal syndrome of Zellweger was found without the characteristic clinical facial signs.     

Noninvasive measurement of gastric accommodation in patients with idiopathic nonulcer dyspepsia

OBJECTIVES: Postprandial symptoms are associated with impaired postprandial gastric accommodation. The aims of this study were to apply a noninvasive method to measure accommodation of the entire stomach in healthy subjects and in patients with idiopathic dyspeptic symptoms, and to assess the frequency of abnormal gastric accommodation and emptying of solids in these patients. METHODS: In 20 healthy volunteers and 32 tertiary referral patients, we used i.v. 99mTc-single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes; we expressed the volume response to feeding ("accommodation") as the change in gastric volume and the ratio of postprandial/fasting volumes. The stomach was identified in transaxial SPECT tomographic images using a semiautomated, intensity-based extraction algorithm. Whole gastric volumes were measured using AnalyzeAVW software. Gastric emptying in patients was measured by scintigraphy. We also assessed dyspeptic symptoms and the association with normal or reduced accommodation. RESULTS: SPECT imaging detects the postprandial change in gastric volume ("accommodation") in health and disease. Among healthy subjects (eight men, 12 women), the postprandial/fasting gastric volume ratio was 4.9+/-1.7 (mean +/- SD; fifth through 95th percentiles 3-8, median 4.6). Thirteen (41%) patients with idiopathic nonulcer dyspepsia had reduced postprandial "accommodation." Gastric emptying was fast in four (13%), normal in 25 (78%), and slow in three (9%) patients. Both tests were normal in 50% of patients. Weight loss of >10 pounds tended to be more frequently observed in those with reduced "accommodation" (62% vs 32%, p = 0.09). CONCLUSIONS: SPECT imaging noninvasively measures fasting and postprandial gastric volumes in humans. Half the patients with idiopathic nonulcer dyspepsia had impaired gastric accommodation or emptying. Reduced gastric "accommodation" was observed in 41% of a group with idiopathic nonulcer dyspepsia. Abnormal gastric emptying is less frequent (22%).     

Characterization of Small Intestinal Pressure Waves in Ambulant Subjects Recorded with a Novel Portable Manometric System

The organization of lumen-occlusive pressurewaves is believed to be an important determinant ofluminal flow. At present, little is known about theorganization of small intestinal pressure waves inhumans. The aim of the present study was tocharacterize the spatiotemporal organization of smallintestinal pressure waves using a portable 12-channelmicromanometric system. Small intestinal pressures wererecorded from six duodenal (1 cm apart) and six jejunal(1 cm apart) sites after a standard lunch (1892 kJ) anddinner (3305 kJ) and an overnight fast in seven ambulantsubjects. Postprandially, the number of isolated pressure waves and the number of pressure wavesequences that spanned 1 and 2 cm decreased over time (P= 0.04, P = 0.003, and P = 0.0001) and were higher afterlunch than dinner (P = 0.04, P = 0.02 and P = 0.04), in contrast to the number oflong-spanned pressure wave sequences, which remainedconstant over time and were not influenced by the meal.The number of isolated pressure waves and pressure wave sequences over 1-5 cm recorded in the earlypostprandial period were higher than during the 30-minperiod of nocturnal phase II (P < 0.01). Inconclusion, prolonged recording of small intestinalmotility in ambulant subjects using a perfusedmanometric system is feasible. Postprandial recordingsshowed that the spatiotemporal organization of pressurewaves is time- and meal-dependent.     

C-reactive protein levels during a relapse of Crohn’s disease are associated with the clinical course of the disease

AIM: To explore if C-reactive protein (CRP) levels might serve as a prognostic factor with respect to the clinical course of Crohn's disease and might be useful for classification.METHODS: In this retrospective cohort study we enrolled 94 patients from the inflammatory bowel disease (IBD) database of the University Medical Centre Utrecht. CRP levels during relapse were correlated with the number of relapses per year. Severity of relapses was based on endoscopic reports and prednisone use. Furthermore, patients were categorized in a low or high CRP group based on their CRP response during relapse and demographic and clinical features were compared.RESULTS: Overall, a positive correlation between CRP levels, number of relapses, and severity of relapse was found (respectively rs = 0.31, P < 0.01 and rs = 0.50, P < 0.001). Employing a cut-off level of 15 mg/L, the index CRP level was found to discriminate patients with respect to the number of relapses per year, as well as for severity of relapses (respectively 0.25 ± 0.16 vs 0.36 ± 0.24, P < 0.05 and 4.4 ± 1.2 vs 3.2 ± 1.1 on a 10-point visual analogue scale, P < 0.001 for the high CRP and low CRP groups respectively). In addition, the high CRP group showed more cumulative days of prednisone use per year (107 ± 95 vs 58 ± 48, P < 0.05), as well as a better response to infliximab (93 % vs 33 %, P = 0.06).CONCLUSION: A higher CRP level during relapse seems to be associated with a more severe clinical course of disease.     

C-reactive protein levels during a relapse of Crohn＇s disease are associated with the clinical course of the disease

AIM： TO explore if C-reactive protein （CRP） levels might serve as a prognostic factor with respect to the clinical course of Crohn＇s disease and might be useful for classification. METHODS： In this retrospective cohort study we enrolled 94 patients from the inflammatory bowel disease （IBD） database of the University Medical Centre Utrecht. CRP levels during relapse were correlated with the number of relapses per year. Severity of relapses was based on endoscopic reports and prednisone use. Furthermore, patients were categorized in a low or high CRP group based on their CRP response during relapse and demographic and clinical features were compared. RESULTS： Overall, a positive correlation between CRP levels, number of relapses, and severity of relapse was found （respectively rs = 0.31, P 〈 0.01 and rs = 0.50, P 〈 0.001）. Employing a cut-off level of 15 mg/L, the index CRP level was found to discriminate patients with respect to the number of relapses per year, as well as for severity of relapses （respectively 0.25 ± 0.16 vs 0.36 ± 0.24, P 〈 0.05 and 4.4 ± 1.2 vs 3.2 ± 1.1 on a 10-point visual analogue scale, P 〈 0.001 for the high CRP and low CRP groups respectively）. In addition, the high CRP group showed more cumulative days of prednisone use per year （107 ± 95 vs 58 ± 48, P 〈 0.05）, as well as a better response to infiiximab （93 % vs 33 %, P = 0.06）. CONCLUSION： A higher CRP level during relapse seems to be associated with a more severe clinical course of disease.     

Effect of proton-pump inhibitor treatment on symptoms and quality of life in GERD patients depends on the symptom-reflux association

BACKGROUND: Gastroesophageal reflux disease patients demonstrate various pathophysiologic backgrounds. Therefore, a heterogeneous response to proton-pump inhibitor (PPI) treatment can be expected. We investigated the effect of short-term PPI treatment on symptoms and quality of life (QOL) in primary care patients with and without pathologic esophageal acid exposure and in presence or absence of a positive association between symptoms and reflux episodes. STUDY: Seventy-four heartburn patients were categorized into 4 groups according to positive or negative symptom-reflux association, as expressed in symptom index, symptom sensitivity index, and symptom association probability (SAP) and presence or absence of pathologic reflux, defined as esophageal pH<4%>6% of the time (pH+/pH-). Overall and specific reflux symptoms were assessed 1 week before and the last week during a 2-week course of 40-mg esomeprazole daily. The QOL was scored by the Quality of Life in Reflux and Dyspepsia questionnaire 2 weeks before treatment and directly after. RESULTS: Using the SAP to assess symptom-reflux associations, the 4 groups [SAP+pH+(n=40); SAP+pH-(n=12); SAP-pH+(n=10); SAP-pH-(n=10)] had similar demographic characteristics. The SAP-pH- subgroup had the least overall symptom reduction (P<0.01) and in the SAP+pH+ subgroup the greatest heartburn symptom reduction was found (P<0.02). The residual symptom scores on treatment were lowest in SAP+pH+ and highest in SAP-pH- subgroups and relatively high in the SAP+pH-. QOL was severely reduced and SAP-pH- patients had the lowest QOL overall. Similar findings were made using symptom index and symptom sensitivity index. CONCLUSIONS: Symptomatic reflux patients without evidence of reflux disease on a 24-hour pH recording responded less favorably to PPI treatment than patients with a positive symptom-reflux association or with pathologic reflux.     

Characterization of ectopic lymphoid structures in different types of acute renal allograft rejection

We hypothesize that T cells such as interleukin (IL)‐21⁺B cell lymphoma 6 (BCL6)⁺ T follicular helper cells can regulate B cell‐mediated immunity within the allograft during acute T cell‐mediated rejection; this process may feed chronic allograft rejection in the long term. To investigate this mechanism, we determined the presence and activation status of organized T and B cells in so‐called ectopic lymphoid structures (ELSs) in different types of acute renal allograft rejection. Biopsies showing the following primary diagnosis were included: acute/active antibody‐mediated rejection, C4d⁺ (a/aABMR), acute T cell‐mediated rejection grade I (aTCMRI) and acute T cell‐mediated rejection grade II (aTCMRII). Paraffin sections were stained for T cells (CD3 and CD4), B cells (CD20), follicular dendritic cells (FDCs, CD23), activated B cells (CD79A), immunoglobulin (Ig)D, cell proliferation (Ki67) and double immunofluorescent stainings for IL‐21 and BCL6 were performed. Infiltrates of T cells were detected in all biopsies. In aTCMRI, B cells formed aggregates surrounded by T cells. In these aggregates, FDCs, IgD and Ki67 were detected, suggesting the presence of ELSs. In contrast, a/aABMR and aTCMRII showed diffuse infiltrates of T and B cells but no FDCs and IgD. IL‐21 was present in all biopsies. However, co‐localization with BCL6 was observed mainly in aTCMRI biopsies. In conclusion, ELSs with an activated phenotype are found predominantly in aTCMRI where T cells co‐localize with B cells. These findings suggest a direct pathway of B cell alloactivation at the graft site during T cell mediated rejection.