Bile acids aspiration reduces survival in lung transplant recipients with BOS despite azithromycin.

Azithromycin (AZM) improved bronchiolitis obliterans syndrome (BOS) and reduced aspiration in lung transplant (LTx) recipients. We hypothesize that AZM could improve graft and overall survival more efficiently in LTx patients with BOS who have bile acid (BA) aspiration by protecting against the aspiration-induced progression of BOS. The goal was to compare FEV(1) (% baseline), BOS progression and overall survival in LTx recipients treated with AZM for BOS, both with versus without BA aspiration. Therefore, LTx recipients treated with AZM for BOS were recruited and broncho-alveolar lavage (BAL) samples were analyzed for the presence of BA and neutrophilia before the start of AZM treatment. Short-term effect of AZM on FEV(1) and BAL neutrophilia was assessed, progression of BOS and survival were followed-up for 3 years and results were compared between patients with/without BA aspiration. 19/37 LTx patients had BA in BAL. BA aspiration predisposed to a significantly worse outcome, in terms of decline in FEV(1) , progression of BOS ≥ 1 and survival. AZM does not seem to protect against the long-term allograft dysfunction caused by gastroesophageal reflux (GER) and aspiration and an additional treatment targeting aspiration may be indicated in those LTx patients.

Characteristics of gastroesophageal reflux and potential risk of gastric content aspiration in children with cystic fibrosis.

OBJECTIVES: Increased gastroesophageal reflux (GER) is common in children with cystic fibrosis (CF). We studied the occurrence of acid, weakly acidic (WA), and weakly alkaline (WALK) reflux in children with CF and evaluated a possible surrogate marker for risk of gastric content aspiration. PATIENTS AND METHODS: Twenty-four children with CF underwent impedance-pH monitoring for detection of acid (pH < 4), WA (pH 4-7), and WALK-GER (pH > or = 7). In 11 children, cough was objectively recorded with esophageal manometry and the symptom association probability was calculated to determine the reflux-cough relation. Presence of bile acids (BA) was measured in the saliva of 65 patients with CF and 23 healthy children, respectively. RESULTS: Sixteen of the 24 children had increased GER (esophageal acid exposure). The majority of reflux events were acidic in nature. WA reflux was less common and WALK reflux was rare. The sequence reflux-cough was found in 8 of the 11 children and 1 of 11 children had a positive symptom association probability for reflux-cough. The sequence cough-reflux was found in only 3 of the 11 children. Only a small fraction of the total esophageal acid and volume exposure was secondary to cough. Twenty-three of the 65 children with CF had BA in saliva compared with none of the healthy controls. CONCLUSIONS: Although WA-GER is uncommon, acid GER is prevalent in children with CF. It is a primary phenomenon and is not secondary to cough. One third of the children with CF have BA in saliva, which may indicate an increased risk for aspiration. However, the impact of salivary BA and potential aspiration on CF pulmonary disease needs further investigation.

Azithromycin reduces gastroesophageal reflux and aspiration in lung transplant recipients.

Azithromycin (AZI) is a macrolide antibiotic that improves lung function in lung transplant recipients (LTx). Gastroesophageal reflux (GER) has been implicated in the pathogenesis of chronic rejection after LTx. Macrolide antibiotics may affect GER by modifying esophageal and gastric motility. The purpose of this study was to evaluate the effect of AZI on GER and gastric aspiration after LTx. Acid and weakly acidic GER was measured with 24-h pH-impedance monitoring in 47 LTx patients (12 patients "on" AZI). Gastric aspiration was assessed in a separate group of 30 LTx patients before and after AZI by measurements of pepsin and bile acid in bronchoalveolar lavage fluid (BALF). Patients "on" AZI had a significant lower total number of reflux events [41 (30-61) vs. 22.5 (7-37.5)], number of acid reflux events [24 (16-41) vs. 8 (4-18)], esophageal acid exposure [2.9% (0.7-7.3) vs. 0.2% (0.1-2.0)], bolus exposure [0.73% (0.5-1.4) vs. 0.21% (0.12-0.92)], and proximal extent of reflux [14 (9-24) vs. 5 (2-7)]. AZI reduced the concentration of bile acids in BALF without affecting levels of pepsin. LTx patients "on" AZI have less GER and bile acids aspiration. This effect might be due to enhanced esophageal motility and accelerated gastric emptying.

Gastro-oesophageal reflux and aspiration of gastric contents in adult patients with cystic fibrosis.

BACKGROUND: Gastro-oesophageal reflux (GOR) is increased in cystic fibrosis (CF), but its prevalence, characteristics, association with gastric aspiration and respiratory impact are not well characterised. We investigated acid and weakly acidic reflux, aspiration and respiratory symptoms/function in adult CF patients. METHODS: Thirty-three CF patients [19 men; 29 (18-55) years, [10 post-lung transplant (LTx)] underwent impedance-pH monitoring for detection of acid (pH<4) and weakly acid GOR (pH 4-7). In 16 patients cough was objectively recorded with oesophageal manometry, and the symptom association probability (SAP) was calculated. Saliva and bronchoalveolar lavage fluid (BALF) were tested for bile acids. RESULTS: Twenty-eight patients had increased GOR (21 acid, 5 weakly acidic and 2 acid+weakly acidic) and 10 had a positive SAP for reflux cough. GOR parameters were similar in non-LTx and post-LTx CF patients. The sequence reflux cough was significantly more common than cough reflux. Sixteen of 38 patients had bile acids in saliva and 6/10 in BALF and this was almost exclusively observed in patients with genotype DF508/DF508. Only 12/28 with increased GOR and 9/22 with bile acids in saliva/BALF had typical reflux symptoms. There was a positive correlation (r = 0.53, p = 0.03) between oesophageal acid exposure and cough. SAP-positive patients with for reflux cough had a lower lung function than SAP-negative patients. CONCLUSION: Increased GOR is prevalent in CF and not secondary to cough. Acid GOR is common, but weakly acidic GOR may also occur. CF patients have a high risk of aspiration and reflux seems to be associated with more cough and poorer lung function. Outcome studies with intense anti-reflux therapy are needed to confirm the deleterious role of reflux in CF progression.

Short exposure of oesophageal mucosa to bile acids, both in acidic and weakly acidic conditions, can impair mucosal integrity and provoke dilated intercellular spaces.

BACKGROUND: Severe duodeno-gastro-oesophageal reflux (DGOR) is a risk factor for oesophagitis and Barrett's oesophagus. Patients with non-erosive reflux disease (NERD) have a slight increase in DGOR. Patients with gastro-oesophageal reflux disease (GORD), who are taking proton pump inhibitors (PPIs), still have reflux but of weakly acidic pH and persistence of bile. In these two groups of patients, heartburn might be due to increased oesophageal mucosal permeability and dilated intercellular spaces (DIS). We aimed to assess whether experimental short exposure of the oesophageal mucosa to bile acids, in low concentrations (at acidic, weakly acidic and neutral conditions) can increase mucosal permeability and provoke DIS. METHODS: Rabbit oesophageal mucosa was studied in diffusion and Ussing chambers. We assessed the effects of different solutions containing bile acids, applied to the mucosal side, on transepithelial electrical resistance (R(T)) and permeability to fluorescein. The diameter of intercellular spaces was assessed by using transmission electron microscopy. RESULTS: Incubation of oesophageal mucosa with acidic solutions (pH 2.0) containing a range of bile acids (0.5-5 mmol/l) markedly decreased R(T) and increased mucosal permeability. Weakly acidic solutions (pH 5.0), and to some extent neutral solutions (pH 7.4), containing some bile acids also decreased R(T) and increased permeability, although the effects were much less marked and in some combinations no effect was seen. Exposure to bile acids provoked DIS in acid and weakly acidic conditions but not in neutral (pH 7.4) solutions. CONCLUSIONS: Experimental short exposure of the oesophageal mucosa to solutions with a bile acid concentration and acidity similar to that observed in the gastric contents of patients with NERD or ERD, and who are taking PPIs, may impair oesophageal mucosal integrity and even induce dilated intercellular spaces. Such a situation could, theoretically, underlie the occurrence and/or persistence of symptoms in these patients.

Gastro-oesophageal reflux and gastric aspiration in lung transplant patients with or without chronic rejection.

Acid gastro-oesophageal reflux (GOR) and gastric aspiration have been labelled as risk factors for chronic rejection bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). The present study aimed to further characterise GOR (both acid and nonacid) and the degree of gastric aspiration in LTx recipients both with and without BOS. Impedance-pH recordings were used for GOR detection. Pepsin and bile acid levels were measured in bronchoalveolar lavage fluid (BALF). A total of 48% of patients had increased GOR, of which 27% had exclusively increased nonacid reflux. Cystic fibrosis patients had the highest prevalence of GOR. Pepsin was found in BALF of all patients and bile acids in BALF of 50% of the patients. Patients with BOS had neither increased GOR nor elevated pepsin in BALF. However, 70% of the patients with BOS had bile in BALF compared with 31% of stable patients. Proton pump inhibitor (PPI) treatment reduced acid reflux but did not affect nonacid reflux. Moreover, pepsin and bile levels in BALF were not reduced by PPI. One-half of the lung transplant patients had increased reflux, and nonacid reflux was common. Gastric aspiration occurred in most lung transplant patients. Pepsin was a more general marker and bile acids a more specific marker that might be associated with bronchiolitis obliterans syndrome. Proton pump inhibitor treatment did not prevent nonacid reflux and gastric aspiration.

Synthetic dyes decolourisation by white-rot fungi: Development of original microtitre plate method and screening.

A microtitre plate-based method was developed for a fast screening of numerous fungal strains for their ability to decolourise textile dyes. In 3 days, this method allowed to estimate significant fungal decolourisation capability by measuring the absorbance decrease on up to ten dyes. More than 325 white-rot fungi (WRF) strains belonging to 76 fungal genera were compared with regards to their capability to decolourise five azo and two anthraquinone dyes as well as the dyes mixture. The most recalcitrant dyes belonged to the azo group. Several new species unstudied in the bioremediation field were found to be able to efficiently decolourise all the dyes tested.

Note: Internal diamagnetic flux measurements on ASDEX Upgrade.

Internal diamagnetic flux measurements, with measurement loops and compensation magnetic probes inside the vacuum vessel, are now available on the ASDEX Upgrade tokamak. The measured diamagnetic flux is compared to that predicted by simulations and calculated from equilibrium reconstruction. The diamagnetic flux measured at 2 positions separated toroidally by 180° in the vacuum vessel is compared.

Improved diagnosis of gastro-oesophageal reflux in patients with unexplained chronic cough.

BACKGROUND: Symptoms, oesophageal pHmetry and proton pump inhibitor treatment are used for diagnosing gastro-oesophageal reflux-related cough. Weakly acidic reflux is now increasingly associated with reflux symptoms such as regurgitation or chest pain. AIM: To study the association between weakly acidic reflux and cough in a selected, large group of patients with unexplained chronic cough. METHODS: A total of 100 patients with chronic cough (77 'off' and 23 'on' a proton pump inhibitor) were studied using impedance-pHmetry for reflux detection and manometry for objective cough monitoring. Symptom Association Probability (SAP) Analysis characterized the reflux-cough association. RESULTS: Acid reflux could be a potential mechanism for cough in 45 patients (with either heartburn, high acid exposure or +SAP for acid reflux). Weakly acidic reflux could be a potential mechanism for cough in 24 patients (with either increased oesophageal volume exposure, increased number of weakly acidic reflux or +SAP for weakly acidic reflux). Reflux could not be identified as a potential mechanism for cough in 31 patients. CONCLUSION: A positive association between cough and weakly acidic reflux was found in a significant subgroup of patients with unexplained chronic cough. Impedance-pH-manometry identified patients in whom cough can be related to reflux that would have been disregarded using the standard diagnostic criteria for acid reflux.

Spring-driven high speed valve for massive gas injection in tokamaks.

A new high speed gas valve was developed for disruption mitigation studies in the tokamak ASDEX Upgrade. The valve was designed to operate inside the vacuum vessel to reduce the time of flight of the injected gas and to prevent dispersion of the gas cloud before the gas reaches the plasma. A spring-driven mechanism was chosen for the valve as it is robust against the high magnetic fields and electromagnetic disturbances inside the vessel. The internal gas reservoir (128 cm3) of the valve, which holds the mitigation gas, is opened within 1.5 ms, and the maximal stroke between the valve plate and nozzle (diameter 13 mm) is 4.5 mm. This allows a peak flow rate of 72 kPam3/s after 1 ms which was determined both analytically and numerically. The highest gas velocity (approximately 560 m/s) is reached 0.6 ms after the valve is opened. The gas cloud expands in a pear shape with an opening angle of 49°.

Real-time diamagnetic flux measurements on ASDEX Upgrade.

Real-time diamagnetic flux measurements are now available on ASDEX Upgrade. In contrast to the majority of diamagnetic flux measurements on other tokamaks, no analog summation of signals is necessary for measuring the change in toroidal flux or for removing contributions arising from unwanted coupling to the plasma and poloidal field coil currents. To achieve the highest possible sensitivity, the diamagnetic measurement and compensation coil integrators are triggered shortly before plasma initiation when the toroidal field coil current is close to its maximum. In this way, the integration time can be chosen to measure only the small changes in flux due to the presence of plasma. Two identical plasma discharges with positive and negative magnetic field have shown that the alignment error with respect to the plasma current is negligible. The measured diamagnetic flux is compared to that predicted by TRANSP simulations. The poloidal beta inferred from the diamagnetic flux measurement is compared to the values calculated from magnetic equilibrium reconstruction codes. The diamagnetic flux measurement and TRANSP simulation can be used together to estimate the coupled power in discharges with dominant ion cyclotron resonance heating.

Adenocarcinoma of the rectum with a solitary metastasis to the urethra in a female.

Adenocarcinoma of the urethra is extremely rare, constituting 10 to 20% of all primary urethral malignancies in women. As in men, the squamous carcinoma accounts for 70% of all urethral tumours. Adenocarcinomas are mostly primary lesions, originating from the paraurethral glands. A case is reported about a female patient, presenting with a mucinous urethral adenocarcinoma, presumably secondary to a primary rectal adenocarcinoma.

Gastric emptying and different types of reflux in adult patients with cystic fibrosis.

BACKGROUND: Increased gastro-oesophageal reflux (GER) is common in patients with cystic fibrosis (CF). Previous studies showed delayed gastric emptying (GE) and a high prevalence of bile acids in saliva suggesting duodenogastro-oesophageal reflux (DGER). AIM: To assess different types of reflux (acid, weakly acidic and bile) and their relationship with rate of GE in adult CF patients. METHODS: Gastric emptying was assessed in 33 CF patients using breath tests, reflux was monitored in 42 patients using impedance-pH-metry and 14 CF patients underwent combined impedance-pH-Bilitec monitoring. RESULTS: Delayed GE was found in 33%, increased GER (predominantly acid) in 67% and pathological DGER in 35% of the CF patients. There was a significant correlation between oesophageal bile and acid exposure (P < 0.0001, r = 0.85). Patients with increased DGER had a higher proximal extent of reflux compared to those without DGER [17 (9-35) vs. 5 (1-12), P = 0.04]. There was no correlation between GE and reflux parameters, however, in a subgroup of 10 patients studied by impedance-pH-Bilitec and GE, there was a strong correlation between GE rate and bile exposure (P = 0.005, r = 0.83). CONCLUSIONS: Delayed gastric emptying is present in 1/3 of patients with cystic fibrosis. There is a subgroup of these patients with both delayed gastric emptying and increased acidic duodenogastro-oesophageal reflux with high proximal extent and risk of aspiration. Controlled studies should be performed to evaluate the effect of prokinetics or antireflux surgery on the clinical cystic fibrosis evolution in these patients.

The relationship between gastroesophageal reflux and cough in children with chronic unexplained cough using combined impedance-pH-manometry recordings.

INTRODUCTION: Assessment of the reflux-cough association in children is challenging. Esophageal (impedance) pH recording is sensitive to recognize reflux. However, cough recorded by an event marker, possibly lacks accuracy. We aimed to study the exact time relationship between reflux and cough in children with chronic cough. METHODS: Twenty-six children (12 boys; 1-10.5 years) with chronic unexplained cough underwent ambulatory impedance-pH-manometry recordings. Manometry was used for precise cough recognition. Reflux was assessed with impedance-pH monitoring and defined as acid (pH <4), weakly acidic (WA) (pH 4-7), weakly alkaline (WALK) (pH ≥7), or acid only (pH <4 for ≥4 sec without impedance pattern). Cough was considered "induced by" reflux, if it started ≤2 min after reflux. The Symptom Association Probability (SAP) was calculated and considered positive if >95%. Cough-induced reflux if it occurred 30 sec before the reflux event. RESULTS: Impedance-pH detected 30 (21-52) reflux episodes/patient (55.2% acid, 41.5% WA, and 3.3% WALK). Additionally 59 acid only events were identified [1 (0-21)/patient]. Manometry detected 47 (5-203) cough bursts/patient. Reflux-cough was found in 22/26 patients. Ten patients had a +SAP for reflux-cough (one acid, six WA, and three acid + WA gastroesophageal reflux [GER]), of which nine had a normal acid exposure. Six out of 10 patients with +SAP using manometry had a +SAP using the event marker. Cough-reflux was detected in 19 patients [3 (0-7)/patient]. Only a small fraction of the esophageal acid exposure [9.6 (0.4-31.8%)] was secondary to cough. CONCLUSION: Both acid and WA GER may precede cough in children with unexplained cough, but cough does not induce GER. Objective cough recording improves symptom association analysis.