- Email: [email protected]
24-hour ambulatory esophageal manometry in patients with achalasia of the esophagus
April 1995
Esophageal, Gastric, and Duodenal Disorders
• TRIGLYCERIDE BIOSYNTHESIS AND SECRETION BY RAT GI MUCOSA. E.J. Dial and L.M. Lichtenberger. Department of Physiology and Cell Biology, University of Texas Medical School, Houston TX. Neutral lipids have been localized histochemically in the surface mucous cells of the gastric and duodenal mucosae, where they may play a role in gastroduodenal protection (Gastroenterology 101:7-21,1991). We investigated: 1) the ability of these and other GI tissues to synthesize triglyceride (TG) de novo, and 2) the effects of lipidic and non-lipidic meals on TG biosynthesis and secretion. For Study 1, rat GI tissues were incubated in vitro with 3H-palmitic acid (PA) for 2h at 37 ° CI extracted for total lipid, and separated by thin layer chromatography (TLC) for neutral lipids. For Study 2, rats received orally either saline, skim milk, or whole milk (3.5% fat), followed 1.75 h later by 3H-PA. After another 15min, gastric fluid and tissue were collected, extracted for lipid, and separated by TLC. The results of Study 1 showed that the greatest TG synthetic activity was located in the esophagus, antrum, and duodenum. The tongue, oxyntic mucosa, and distal small and large bowel possessed lesser TG synthetic activity. Ingestion of skim and whole milk in Study 2 resulted in 3- and I0-fold increases in the appearance of 3H-TG in the gastric juice, and 0- and 2-fold decreases in 3HTG in gastric tissue, respectively. Incubation of 3H-PA and milk m vitro did not form 3H-TG. However, collection of gastric juice 1.75 hailer oral dosing with saline or milk, and in vitro incubation of this juice with 3H-PA, resulted in a clear 4-fold generation of TG in vitro as determined by 3H-labelling. Conclusions: 1) TG is synthesized t e a greater extent by non-acid secreting, upper GI tissues which are normally exposed to gastric acid or exogenous challenges; 2) gastric mucosa is stimulated by the presence of food to increase the secretion and biosynthesis of TG, which occurs in part in the GI lumen; 3) lipid-containing food stimulates TG secretion from gastric mucosa more than lipid-free food; and 4) these results are consistent with a role for endogenous and diet-induced TG synthesis and secretion in protection of the GI tract. (Supported by NRICGP/USDA grant 92-37200-7651).
• 24-HOUR AMBULATORY ESOPHAGEAL MANOMETRY IN PATIENTS" WITH ACHALASIA OF THE ESOPHAGUS. N. Di Martino, *M. Bortolott~ V. Maffettone~ G. 1~o, L Monaco and A. Del Genie. Dept. of Digestive Surgery, 2~ University o f Naples - * 1"~Medical Clinic, University o f Bologna - 1TALE
Absence of the peristaltic enntraetioas in the esophageal body and the failure of the lower esophageal sphincter (LES) pesLdeglutitive relaxation are the mean motor disturbances in patients with aehalasia. These alterations were usually evidenced by means stationary esophageal mannmetry, which is able to record for a brief period. A I M OF THE WORK: to study the circadian esophageal motor activity of the esophageal body in patients with aehalasia, using a non-perfnsed ambulatory manometry system. MATERIALS AND METHODS: ten patients (Pts) with unheated esophageal aehalasia (dilatation < 5 em) had an 24-hoar ambulatory esophageal manometry. The portable recording system enusistad of a computerized data logger (Miurodigitrapper; Syneeties) and a probe with 4 mierotrausducers 5 em apart (Konigsberg; USA), the distal one being positioned 5 em above the LES. A miurotranaducer, positioned 1 em below the upper esophageal sphincter, recorded the swallow activity. Contractions frequency (I) (n°/min), mean amplitude (II) (mmHg), mean duration of contraction (HI) (see), % of contraction > 7 see. (IV), % of multipeaked (V), repetitive (VI) and isolated (VII) contractions, % of peristaltic (VIII) end simultaneous (IX) sequences were evaluated and analyzed during the following periods: a) meal-time (MT); b) upright (UP); c) supine night-time (NT). On the basis of the relationship with swallows the enntraetion events were classified as postdeglutifive (PD) or spontaneous (S).The data out of a group of 65 normal subjects were used as eonffol . Student's t-test and Wilcoxon's rank-sum test were used for statistical analysis. RESULTS: (see table I): Table tt & PATIENTS WITH ACHALASIA w CONTROL GROUP
1
II
III
IV
V
VI
VII
VIII IX
PD
S
NT NS ,1, ,1, 1" NS NS NS ,b 1" $ t *~ai~eam;,I,l"~e~, or le=mteo/'/mtm, ya/u~vf~r,*ro/tro~,~ d , ntt'~r t~t a d ~ma/j,sk ofvar/a~(X~- p • 0.05). Peristaltic sequences were detected in all patients. 27.8±12.6% on the total, and the 19.5+11.06% of these was complete. Moreover primary peristaltic sequences were pr~ent in 33.1:v23.4% of all pexistaltiesequences. CONCLUSIONS: in contrast to the current knowledgments, our results show surprisingly the presence of peristaltis activity in pts with aehalasia (27.9% Mr, 26.9% UP, 28.1% NT). We believe these results are
related both with the use of ambulatory system, which allow a 24-hour monitoring and with miorotransducors, which are able to detect motor events with much accuracy. These motor events are usually not detectable by stationary perilled system. l) Bortolotti M. et al. Neurogastroenterology and MotHtty, 6.'1-4, 1994.
~INFLUENCE GASTRITIS ECL CELL PROLONGED
A83
OF THE DEGREE OF SEVERITY OF FUNDIC ON SERUM GASTRIN CONCENTRATION AND DENSITY IN CONTROLS AND DURING TREATMENT WITH ANTISECR~Ry DRUGS.
Diebold M.D.*, Richardson S.**, Zeitoun P.*, Duchateau A.*, Bigard M.A., Colin R., Cortot A., and colleagues in 52 centers. * C.H.U. Reims, ** Unit 170 INSERM, France. The d e g r e e of fundic g a s t r i t i s was one of the factors evaluated in a study comparing the density of ECL cells and basal serum gastrin concentration (BSGC) in control subjects and patients treated long term with antisecretory drugs. Patients and m e t h o d s . Four proximal fundic biopsies were carried out in s u b j e c t s treated with omeprazole (OME, n=20!), with an H2-receptor antagonist (H2RA, n=ll8) and in control subjects with normal upper GI tract endoscopy (C, n=215). The w h i t e h e a d classification was e m p l o y e d in evaluating fundic gastritis, i.e. absent (GO), superficial (GI), i n t e r s t i t i a l (G2), and atrophic (G3).The ECL cells (Grimelius method) were counted per unit field. The BSGC was determined. The r e l a t i o n s h i p s b e t w e e n g a s t r i t i s severity, BSGC and d e n s i t y of ECL cells w e r e determined by correlation tests and/or analyses of variance and covariance after logarithmic transformation of the 2 variables. R e s u l t s : the distribution of fundic gastritis was as follows : OME: GI=23,62%, G2=8,04%, G3=I,01% H2RA: GI=23,93%, G2=II,97%, G3=3,42% C: GI=33,02%, G2=II,16%, G3=4,65% The ECL cell density was similar in the OME and H2RA groups and significantly higher than in the C group (p=0,0009 and p=0,035 respectively). In each group the ECL cell density increased as the BSCG increased (p=0,0001), It was significantly higher in atrophic gastritis (G3) but was not clearly related to fundic gastritis (GI.G2).Conclusion : The degree of severity of fundic gastritis, atrophy excepted, has little effect on ECL cell p o p u l a t i o n density in controls as in OME and H2RA treated patients.
• ADAPTATION OF THE GASTRIC EPITHELIUM TO INJURY IS INDEPENDENT OF NEURONAL AND HUMERAL FACTORS BUT HAS A TGF-a-DEPENDENT COMPONENT. K. Doljanin, A.S, Giraud, M.V. Skeljo, N.D. Yeomans. University of Melbourne, Department of Medicine, Western Hospital, Australia. The progressive reduction in gastric mucosal damage after repeated dosing of injurious agents like NSAIDS is termed adaptation. NSAID-induced adaptation confers cross-tolerance to ethanol injury in vivo.This study aimed to determine whether adaptation is an intrinsic property of the gastric epithelium, independent of neuronal and humeral influences, and whether the gut mitogen TGFtx plays a role in its development. Rats (n=5/group) were treated daily with : methylcellulose (MC) for 6 days, MC for 5 days and the NSAID diclofenac (DCF, 10 mg/kg) on the 6th day, or DCF for 6 days. Antral mucosa was taken for organ culture and loaded with 51Cr. Cultured explants were challenged with ethanol for 60 min and damage quantified by 5~Cr release into medium. Explant viabilitywas confirmed by the linear incorporation of 3H-leucine into protein over 16 hr. In a separate experiment, rats (n=7/group) treated with DCF or vehicle as above, but for 7 days, were sacrificed 4 hr after the final dose, the gastric mucosa extracted and TGFa quantified by RIA. Gastric damage (the proportion (%) of total 5~Cr released in 60 min) and tissue TGFcz (mean + SE) for each dose group is given below: Pro-treatment Ethanol concentration TGF-a 0% 20% 30 (fmol/mg protein) Vehicle(MC) 10.3+0.4 36.7+3.3 41.7_+2.2 92.9_+10.9 DCF x 1 18.9+4.0 36.2_+3.5 34.5_+4.4 95.1_+14.6 DCFx 6 16.4_+0.6 19.5+2.5" 19.4+3.8" 218.1_+34.3# Control (no dose) 98.7+23.3 *P<0.01(ANOVA) vs. other ethanol groups. #P<0,05 (t-test) vs. other groups. The rate of 5~Crrelease was significantly lower in ethanol-injured explants from rats previously adapted to diclofenac compared to those exposed to a single damaging dose of diclofenac, or vehicle only. The concentration of TGFa was significantly higher in the gastric epithelium of rats adapted to diclofenac than in other groups. Conclusions: (1) Cross adaptation of the gastric mucosa to injury is demonstrable by antral mucosal explants in organ culture (2) TGF-a peptide expression is up-regnlated in the adapted gastric mucosa. Together these findings suggest that adaptation is an intrinsic property of the gastric epithelium and that TGF-cc may play a role in its maintenance.
Esophageal, Gastric, and Duodenal Disorders
• TRIGLYCERIDE BIOSYNTHESIS AND SECRETION BY RAT GI MUCOSA. E.J. Dial and L.M. Lichtenberger. Department of Physiology and Cell Biology, University of Texas Medical School, Houston TX. Neutral lipids have been localized histochemically in the surface mucous cells of the gastric and duodenal mucosae, where they may play a role in gastroduodenal protection (Gastroenterology 101:7-21,1991). We investigated: 1) the ability of these and other GI tissues to synthesize triglyceride (TG) de novo, and 2) the effects of lipidic and non-lipidic meals on TG biosynthesis and secretion. For Study 1, rat GI tissues were incubated in vitro with 3H-palmitic acid (PA) for 2h at 37 ° CI extracted for total lipid, and separated by thin layer chromatography (TLC) for neutral lipids. For Study 2, rats received orally either saline, skim milk, or whole milk (3.5% fat), followed 1.75 h later by 3H-PA. After another 15min, gastric fluid and tissue were collected, extracted for lipid, and separated by TLC. The results of Study 1 showed that the greatest TG synthetic activity was located in the esophagus, antrum, and duodenum. The tongue, oxyntic mucosa, and distal small and large bowel possessed lesser TG synthetic activity. Ingestion of skim and whole milk in Study 2 resulted in 3- and I0-fold increases in the appearance of 3H-TG in the gastric juice, and 0- and 2-fold decreases in 3HTG in gastric tissue, respectively. Incubation of 3H-PA and milk m vitro did not form 3H-TG. However, collection of gastric juice 1.75 hailer oral dosing with saline or milk, and in vitro incubation of this juice with 3H-PA, resulted in a clear 4-fold generation of TG in vitro as determined by 3H-labelling. Conclusions: 1) TG is synthesized t e a greater extent by non-acid secreting, upper GI tissues which are normally exposed to gastric acid or exogenous challenges; 2) gastric mucosa is stimulated by the presence of food to increase the secretion and biosynthesis of TG, which occurs in part in the GI lumen; 3) lipid-containing food stimulates TG secretion from gastric mucosa more than lipid-free food; and 4) these results are consistent with a role for endogenous and diet-induced TG synthesis and secretion in protection of the GI tract. (Supported by NRICGP/USDA grant 92-37200-7651).
• 24-HOUR AMBULATORY ESOPHAGEAL MANOMETRY IN PATIENTS" WITH ACHALASIA OF THE ESOPHAGUS. N. Di Martino, *M. Bortolott~ V. Maffettone~ G. 1~o, L Monaco and A. Del Genie. Dept. of Digestive Surgery, 2~ University o f Naples - * 1"~Medical Clinic, University o f Bologna - 1TALE
Absence of the peristaltic enntraetioas in the esophageal body and the failure of the lower esophageal sphincter (LES) pesLdeglutitive relaxation are the mean motor disturbances in patients with aehalasia. These alterations were usually evidenced by means stationary esophageal mannmetry, which is able to record for a brief period. A I M OF THE WORK: to study the circadian esophageal motor activity of the esophageal body in patients with aehalasia, using a non-perfnsed ambulatory manometry system. MATERIALS AND METHODS: ten patients (Pts) with unheated esophageal aehalasia (dilatation < 5 em) had an 24-hoar ambulatory esophageal manometry. The portable recording system enusistad of a computerized data logger (Miurodigitrapper; Syneeties) and a probe with 4 mierotrausducers 5 em apart (Konigsberg; USA), the distal one being positioned 5 em above the LES. A miurotranaducer, positioned 1 em below the upper esophageal sphincter, recorded the swallow activity. Contractions frequency (I) (n°/min), mean amplitude (II) (mmHg), mean duration of contraction (HI) (see), % of contraction > 7 see. (IV), % of multipeaked (V), repetitive (VI) and isolated (VII) contractions, % of peristaltic (VIII) end simultaneous (IX) sequences were evaluated and analyzed during the following periods: a) meal-time (MT); b) upright (UP); c) supine night-time (NT). On the basis of the relationship with swallows the enntraetion events were classified as postdeglutifive (PD) or spontaneous (S).The data out of a group of 65 normal subjects were used as eonffol . Student's t-test and Wilcoxon's rank-sum test were used for statistical analysis. RESULTS: (see table I): Table tt & PATIENTS WITH ACHALASIA w CONTROL GROUP
1
II
III
IV
V
VI
VII
VIII IX
PD
S
NT NS ,1, ,1, 1" NS NS NS ,b 1" $ t *~ai~eam;,I,l"~e~, or le=mteo/'/mtm, ya/u~vf~r,*ro/tro~,~ d , ntt'~r t~t a d ~ma/j,sk ofvar/a~(X~- p • 0.05). Peristaltic sequences were detected in all patients. 27.8±12.6% on the total, and the 19.5+11.06% of these was complete. Moreover primary peristaltic sequences were pr~ent in 33.1:v23.4% of all pexistaltiesequences. CONCLUSIONS: in contrast to the current knowledgments, our results show surprisingly the presence of peristaltis activity in pts with aehalasia (27.9% Mr, 26.9% UP, 28.1% NT). We believe these results are
related both with the use of ambulatory system, which allow a 24-hour monitoring and with miorotransducors, which are able to detect motor events with much accuracy. These motor events are usually not detectable by stationary perilled system. l) Bortolotti M. et al. Neurogastroenterology and MotHtty, 6.'1-4, 1994.
~INFLUENCE GASTRITIS ECL CELL PROLONGED
A83
OF THE DEGREE OF SEVERITY OF FUNDIC ON SERUM GASTRIN CONCENTRATION AND DENSITY IN CONTROLS AND DURING TREATMENT WITH ANTISECR~Ry DRUGS.
Diebold M.D.*, Richardson S.**, Zeitoun P.*, Duchateau A.*, Bigard M.A., Colin R., Cortot A., and colleagues in 52 centers. * C.H.U. Reims, ** Unit 170 INSERM, France. The d e g r e e of fundic g a s t r i t i s was one of the factors evaluated in a study comparing the density of ECL cells and basal serum gastrin concentration (BSGC) in control subjects and patients treated long term with antisecretory drugs. Patients and m e t h o d s . Four proximal fundic biopsies were carried out in s u b j e c t s treated with omeprazole (OME, n=20!), with an H2-receptor antagonist (H2RA, n=ll8) and in control subjects with normal upper GI tract endoscopy (C, n=215). The w h i t e h e a d classification was e m p l o y e d in evaluating fundic gastritis, i.e. absent (GO), superficial (GI), i n t e r s t i t i a l (G2), and atrophic (G3).The ECL cells (Grimelius method) were counted per unit field. The BSGC was determined. The r e l a t i o n s h i p s b e t w e e n g a s t r i t i s severity, BSGC and d e n s i t y of ECL cells w e r e determined by correlation tests and/or analyses of variance and covariance after logarithmic transformation of the 2 variables. R e s u l t s : the distribution of fundic gastritis was as follows : OME: GI=23,62%, G2=8,04%, G3=I,01% H2RA: GI=23,93%, G2=II,97%, G3=3,42% C: GI=33,02%, G2=II,16%, G3=4,65% The ECL cell density was similar in the OME and H2RA groups and significantly higher than in the C group (p=0,0009 and p=0,035 respectively). In each group the ECL cell density increased as the BSCG increased (p=0,0001), It was significantly higher in atrophic gastritis (G3) but was not clearly related to fundic gastritis (GI.G2).Conclusion : The degree of severity of fundic gastritis, atrophy excepted, has little effect on ECL cell p o p u l a t i o n density in controls as in OME and H2RA treated patients.
• ADAPTATION OF THE GASTRIC EPITHELIUM TO INJURY IS INDEPENDENT OF NEURONAL AND HUMERAL FACTORS BUT HAS A TGF-a-DEPENDENT COMPONENT. K. Doljanin, A.S, Giraud, M.V. Skeljo, N.D. Yeomans. University of Melbourne, Department of Medicine, Western Hospital, Australia. The progressive reduction in gastric mucosal damage after repeated dosing of injurious agents like NSAIDS is termed adaptation. NSAID-induced adaptation confers cross-tolerance to ethanol injury in vivo.This study aimed to determine whether adaptation is an intrinsic property of the gastric epithelium, independent of neuronal and humeral influences, and whether the gut mitogen TGFtx plays a role in its development. Rats (n=5/group) were treated daily with : methylcellulose (MC) for 6 days, MC for 5 days and the NSAID diclofenac (DCF, 10 mg/kg) on the 6th day, or DCF for 6 days. Antral mucosa was taken for organ culture and loaded with 51Cr. Cultured explants were challenged with ethanol for 60 min and damage quantified by 5~Cr release into medium. Explant viabilitywas confirmed by the linear incorporation of 3H-leucine into protein over 16 hr. In a separate experiment, rats (n=7/group) treated with DCF or vehicle as above, but for 7 days, were sacrificed 4 hr after the final dose, the gastric mucosa extracted and TGFa quantified by RIA. Gastric damage (the proportion (%) of total 5~Cr released in 60 min) and tissue TGFcz (mean + SE) for each dose group is given below: Pro-treatment Ethanol concentration TGF-a 0% 20% 30 (fmol/mg protein) Vehicle(MC) 10.3+0.4 36.7+3.3 41.7_+2.2 92.9_+10.9 DCF x 1 18.9+4.0 36.2_+3.5 34.5_+4.4 95.1_+14.6 DCFx 6 16.4_+0.6 19.5+2.5" 19.4+3.8" 218.1_+34.3# Control (no dose) 98.7+23.3 *P<0.01(ANOVA) vs. other ethanol groups. #P<0,05 (t-test) vs. other groups. The rate of 5~Crrelease was significantly lower in ethanol-injured explants from rats previously adapted to diclofenac compared to those exposed to a single damaging dose of diclofenac, or vehicle only. The concentration of TGFa was significantly higher in the gastric epithelium of rats adapted to diclofenac than in other groups. Conclusions: (1) Cross adaptation of the gastric mucosa to injury is demonstrable by antral mucosal explants in organ culture (2) TGF-a peptide expression is up-regnlated in the adapted gastric mucosa. Together these findings suggest that adaptation is an intrinsic property of the gastric epithelium and that TGF-cc may play a role in its maintenance.