AIM: To investigate the effects of electroacupuncture (EA) at neiguan (PC6) on gastric distention-induced transient lower esophageal sphincter relaxations (TLESRs) and discuss the mechanisms of this treatment. METHODS...AIM: To investigate the effects of electroacupuncture (EA) at neiguan (PC6) on gastric distention-induced transient lower esophageal sphincter relaxations (TLESRs) and discuss the mechanisms of this treatment. METHODS: ProtocolⅠ: Twelve healthy cats underwent gastric distention for 60 min on the first day. Electrical acupoint stimulation was applied at the neiguan or a sham point on the hip in randomized order before gastric distention, on the third day and fifth day. Those cats that underwent EA at neiguan on the fifth day were named "Neiguan Group" and the cats that underwent EA at a sham acupoint on the fifth day were named "Sham Group" (control group). During the experiment the frequency of TLESRs and lower esophageal sphincter (LES) pressure were observed by a perfused sleeve assembly. Plasma levels of gastrin (GAS) and motilin (MTL) were determined by radioimmunoassay. Nitrite/nitrate concentration in plasma and tissues were measured by Griess reagent. The nuclei in the brain stem were observed by immunohistochemistry method of c-Fos and NADPH-d dyeing. Protocol Ⅱ: Thirty six healthy cats were divided into 6 groups randomly. We gave saline (2 mL iv. control group), phaclofen (5 mg/kg iv. GABA-B antagonist), cholecystokinin octapeptide (CCK-8) (1 μg/kg per hour iv.), L-Arginine (200 mg/kg iv.), naloxone (2.5 μmol/kg iv.) and tacrine (5.6 mg/kg ip. cholinesterase inhibitor) respectively before EA at Neiguan and gastric distention. And the frequencies of TLESRs in experimental groups were compared with the control group.RESULTS: ProtocolⅠ: Not only the frequency of gastric distention-induced TLESR in 60 min but also the rate of common cavity during TLESRs were significantlydecreased by EA at neiguan compared to that of sham acupoint stimulation. C-Fos immunoreactivity and NOS reactivity in the solitarius (NTS) and dorsal motor nucleus of the vagus (DMV) were significantly decreased by EA at neiguan compared to that of the sham group. However, the positive nuclei of C-Fos and NOS in reticular formation of the medulla (RFM) were increased by EA at neiguan. Protocol Ⅱ: The inhibited effect of EA at neiguan on TLESR’s frequency was completely restored by pretreatment with CCK (23.5/h vs 4.5/h, P < 0.05), L-arginine (17.5/h vs 4.5/h, P < 0.05) and naloxone(12/h vs 4.5/h, P < 0.05). On the contrary, phaclofen (6/h vs 4.5/h, P > 0.05) and tacrine (9.5/h vs 4.5/h, P > 0.05) did not influence it. CONCLUSION: Electric acupoint stimulation at Neiguan significantly inhibits the frequency of TLESR and the rate of common cavity during TLESR in cats. This effect appears to act on the brain stem, and may be mediated through nitric oxide (NO), CCK-A receptor and mu-opioid receptors. But the GABAB receptor and acetylcholine may not be involved in it.展开更多
The junction between the esophagus and the stomach is a specialized region, composed of lower esophageal sphincter (LES) and its adjacent anatomical structures, the gastric sling and crural diaphragm. Together these s...The junction between the esophagus and the stomach is a specialized region, composed of lower esophageal sphincter (LES) and its adjacent anatomical structures, the gastric sling and crural diaphragm. Together these structures work in a coordinated manner to allow ingested food into the stomach while preventing reflux of gastric contents across the esophago-gastric junction (EGJ) into the esophagus. The same zone also permits retrograde passage of air and gastric contents into esophagus during belching and vomiting. The precise coordination required to execute such a complicated task is achieved by a finely-regulated high-pressure zone. This zone keeps the junction between esophagus and stomach continuously closed, but is still able to relax briefly via input from inhibitory neurons that are responsible for its innervation. Alterations of the structure and function of the EGJ and the LES may predispose to gastroesophageal reflux disease (GERD).展开更多
AIM:To investigate the in vitro effects of pantoprazole on rat lower esophageal sphincter(LES)tone.METHODS:Rats weighing 250-300 g,provided by the Yeditepe University Experimental Research Center(Yü-DETAM),were u...AIM:To investigate the in vitro effects of pantoprazole on rat lower esophageal sphincter(LES)tone.METHODS:Rats weighing 250-300 g,provided by the Yeditepe University Experimental Research Center(Yü-DETAM),were used throughout the study.They were anesthetized before decapitation.LES tissues whose mucosal lining were removed were placed in a stan-dard 30-mL organ bath with a modif ied Krebs solution and continuously aerated with 95% oxygen-5% carbon dioxide gas mixture and kept at room temperature.The tissues were allowed to stabilize for 60 min.Sub-sequently,the contractile response to 10-6 mol/L carba-chol was obtained.Different concentrations of freshly prepared pantoprazole were added directly to the tis-sue bath to generate cumulative concentrations of 5×10-6 mol/L,5×10-5 mol/L,and 1.5×10-4 mol/L.Activi-ties were recorded on an online computer via a 4-channeltransducer data acquisition system using the software BSL PRO v 3.7,which also analyzed the data.RESULTS:Pantoprazole at 5×10-6 mol/L caused a small,but statistically insignif icant,relaxation in the car-bachol-contracted LES(2.23% vs 3.95%).The 5×10-5 mol/L concentration,however,caused a signif icant relax-ation of 10.47% compared with the control.1.5×10-4 mol/L concentration of pantoprazol caused a 19.89% relaxation in the carbachol contracted LES(P<0.001).CONCLUSION:This is the fi rst study to demonstrate that pantoprazole has a relaxing effect in isolated LESs.These results might have signif icant clinical implications for the subset of patients using proton pump inhibitors who do not receive full symptomatic alleviation from gastroesophageal reflux disease.展开更多
AIM:To study the relationship between upper esophageal sphincter (UES) relaxation,peristaltic pressure and lower esophageal sphincter (LES) relaxation following deglutition in non-dysphagic subjects.METHODS:Ten non-dy...AIM:To study the relationship between upper esophageal sphincter (UES) relaxation,peristaltic pressure and lower esophageal sphincter (LES) relaxation following deglutition in non-dysphagic subjects.METHODS:Ten non-dysphagic adult subjects had a high-resolution manometry probe passed transnasally and positioned to cover the UES,the esophageal body and the LES.Ten water swallows in each subject were analyzed for time lag between UES relaxation and LES relaxation,LES pressure at time of UES relaxation,duration of LES relaxation,the distance between the transition level (TL) and the LES,time in seconds that the peristaltic wave was before (negative value) or after the TL when the LES became relaxed,and the maximal peristaltic pressure in the body of the esophagus.RESULTS:Relaxation of the LES occurred on average 3.5 s after the bolus had passed the UES and in most cases when the peristaltic wave front had reached the TL.The LES remained relaxed until the peristaltic wave faded away above the LES.CONCLUSION:LES relaxation seemed to be caused by the peristaltic wave pushing the bolus from behind against the LES gate.展开更多
AIM: To characterize the effects of age on the mechanisms underlying the common condition of esophageal dysphagia in older patients, using detailed manometric analysis. METHODS: A retrospective case-control audit was ...AIM: To characterize the effects of age on the mechanisms underlying the common condition of esophageal dysphagia in older patients, using detailed manometric analysis. METHODS: A retrospective case-control audit was performed on 19 patients aged ≥ 80 years (mean age 85 ± 0.7 year) who underwent a manometric study for dysphagia (2004-2009). Data were compared with 19 younger dysphagic patients (32 ± 1.7 years). Detailed manometric analysis performed prospectively included basal lower esophageal sphincter pressure (BLESP), pre-swallow and nadir LESP, esophageal body pressures and peristaltic duration, during water swallows (5 mL) in right lateral (RL) and upright (UR) postures and with solids. Data are mean ± SE; a P-value < 0.05 was considered significant. RESULTS: Elderly dysphagic patients had higher BLESP than younger patients (23.4 ± 3.8 vs 14.9 ± 1.2 mmHg; P < 0.05). Pre-swallow LESP was elevated in the elderly in both postures (RL: 1 and 4 s P = 0.019 and P = 0.05; UR: P < 0.05 and P = 0.05) and solids (P < 0.01). In older patients, LES nadir pressure was higher with liquids (RL: 2.3 ± 0.6 mmHg vs 0.7 ± 0.6 mmHg, P < 0.05; UR: 3.5 ± 0.9 mmHg vs 1.6 ± 0.5 mmHg, P = 0.01) with shorter relaxation after solids (7.9 ± 1.5 s vs 9.7 ± 0.4 s, P = 0.05). No age-related differences were seen in esophageal body pressures or peristalsis duration. CONCLUSION: Basal LES pressure is elevated and swallow-induced relaxation impaired in elderly dysphagic patients. Its contribution to dysphagia and the effects of healthy ageing require further investigation.展开更多
Background:Achalasia is a primary esophageal motility disorder with potential molecular pathogenesis remaining uncertain.This study aimed to identify the differentially expressed proteins and potential pathways among ...Background:Achalasia is a primary esophageal motility disorder with potential molecular pathogenesis remaining uncertain.This study aimed to identify the differentially expressed proteins and potential pathways among achalasia subtypes and controls to further reveal the molecular pathogenesis of achalasia.Methods:Paired lower esophageal sphincter(LES)muscle and serum samples from 24 achalasia patients were collected.We also collected 10 normal serum samples from healthy controls and 10 normal LES muscle samples from esophageal cancer patients.The 4D label-free proteomic analysis was performed to identify the potential proteins and pathways involved in achalasia.Results:Analysis of Similarities showed distinct proteomic patterns of serum and muscle samples between achalasia patients and controls(both P<0.05).Functional enrichment analysis suggested that these differentially expressed proteins were immunity-,infection-,inflammation-,and neurodegeneration-associated.The mfuzz analysis in LES specimens showed that proteins involved in the extracellular matrix–receptor interaction increased sequentially between the control group,type III,type II,and type I achalasia.Only 26 proteins altered in the same directions in serum and muscle samples.Conclusions:This first 4D label-free proteomic study of achalasia indicated that there were specific protein alterations in both the serum and muscle of achalasia,involving immunity,inflammation,infection,and neurodegeneration pathways.Distinct protein clusters between types I,II,and III revealed the potential molecular pathways associated with different disease stages.Analysis of proteins changed in both muscle and serum samples highlighted the importance of further studies on LES muscle and revealed potential autoantibodies.展开更多
Gastroesophageal reflux(GER)in children is very common and refers to the involuntary passage of gastric contents into the esophagus.This is often physiological and managed conservatively.In contrast,GER disease(GERD)i...Gastroesophageal reflux(GER)in children is very common and refers to the involuntary passage of gastric contents into the esophagus.This is often physiological and managed conservatively.In contrast,GER disease(GERD)is a less common pathologic process causing troublesome symptoms,which may need medical management.Apart from abnormal transient relaxations of the lower esophageal sphincter,other factors that play a role in the pathogenesis of GERD include defects in esophageal mucosal defense,impaired esophageal and gastric motility and clearance,as well as anatomical defects of the lower esophageal reflux barrier such as hiatal hernia.The clinical manifestations of GERD in young children are varied and nonspecific prompting the necessity for careful diagnostic evaluation.Management should be targeted to the underlying aetiopathogenesis and to limit complications of GERD.The following review focuses on up-to-date information regarding of the pathogenesis,diagnostic evaluation and management of GERD in children.展开更多
AIM:To clarify the effects of anti-hypertensive drugs on esophageal contraction and determine their possi-ble relationship with gastro-esophageal reflux disease.METHODS:Thirteen healthy male volunteers were enrolled. ...AIM:To clarify the effects of anti-hypertensive drugs on esophageal contraction and determine their possi-ble relationship with gastro-esophageal reflux disease.METHODS:Thirteen healthy male volunteers were enrolled. Esophageal body peristaltic contractions and lower esophageal sphincter (LES) pressure were measured using high resolution manometry. All subjects were randomly examined on four separate occasions following administrations of nifedipine,losartan,and atenolol,as well as without any drug administration.RESULTS:Peristaltic contractions by the esophageal body were separated into three segments by two troughs. The peak peristaltic pressures in the mid and lower segments of the esophageal body under atenolol administration were signifi cantly higher than those without medication in a supine position. On the other hand,peristaltic pressures under nifedipine administration were lower than those observed without drug ad-ministration. Losartan did not change esophageal body peristalsis. Atenolol elevated LES pressure and slowed peristaltic wave transition,while the effects of nifedip-ine were the opposite. CONCLUSION:Among the anti-hypertensive drugs tested,atenolol enhanced esophageal motor activity,which was in contrast to nifedipine.展开更多
Almost 15 years have passed since the first paper on the possibility of using magnets to prevent gastro-esophageal reflux(GER)was published and so it is time to assess the results obtained with the first magnetic devi...Almost 15 years have passed since the first paper on the possibility of using magnets to prevent gastro-esophageal reflux(GER)was published and so it is time to assess the results obtained with the first magnetic device available on the market,the Linx magnetic sphincter augmentation(MSA)and to consider what other options are forthcoming.MSA demonstrated an anti-reflux activity similar to that of Nissen fundoplication,considered the“gold standard”surgical treatment for GER disease,and caused less gas-bloating and a better ability to allow vomiting and belching.However,unlike Nissen fundoplication,this magnetic device is burdened by complications,which are roughly similar to those of the non-magnetic anti-reflux Angelchik prosthesis,that,after considerable use in the eighties,was shelved due to these complications.It is interesting to note that some of these complications show the same pathophysiological mechanism in both devices.The upcoming new magnetic devices should avoid these complications,as their anti-reflux magnetic mechanism is completely different.The experiments in animals regarding these new magnetic appliances were examined,remarking their advantages and drawbacks,but the way to apply them in surgical practice is long and difficult,although worthy,as they represent the future of magnetic surgery.展开更多
Objectives: In this retrospective analysis, we explored the effect of botulinum toxin A (BTA) injection to treat oropharyngeal dysphagia or esophageal dysfunction caused by diseases of the upper (UES) and lower (LES) ...Objectives: In this retrospective analysis, we explored the effect of botulinum toxin A (BTA) injection to treat oropharyngeal dysphagia or esophageal dysfunction caused by diseases of the upper (UES) and lower (LES) esophageal sphincter. Methods: In total, 48 patients (17 patients with UES disorders, and 31 patients with LES dysfunction;mean age 64 years) were treated between 1996 and 2007 in our hospital. Comorbid diseases as well as maintenance medication were documented to evaluate the overall health status of our patients. The mean duration of symptoms, the number of pre-treatments and the specification of dysphagia were considered. Results: One month after injection, the response rates were 73.3% (UES group) and 76.6% (LES group). Most patients in the UES group received 30-40 units BTA (Botox?) whereas most patients in the LES group were treated with 100 units BTA. In cases of re-injection, 50% of patients in the UES group experienced an escalation of dosage (up to 75 units), whereas the other 50% received the same dosage. The dosages in the LES group were mostly kept constant. Conclusion: Comparing the two groups with esophageal dysfunction of fundamentally different etiologies (UES/LES), a discrepancy in the level of symptom relief, onset and a longer cessation of clinical benefit were observed in the LES group. In this analysis, we were able to show that injection of BTA is an effective and safe treatment for disorders of the UES and LES.展开更多
Idiopathic achalasia is a rare primary motility disorder of the esophagus. The classical features are incomplete relaxation of a frequently hypertensive lower esophageal sphincter (LES) and a lack of peristalsis in th...Idiopathic achalasia is a rare primary motility disorder of the esophagus. The classical features are incomplete relaxation of a frequently hypertensive lower esophageal sphincter (LES) and a lack of peristalsis in the tubular esophagus. These motor abnormalities lead to dysphagia, stasis, regurgitation, weight loss, or secondary respiratory complications. Although major strides have been made in understanding the pathogenesis of this rare disorder, including a probable autoimmune mediated destruction of inhibitory neurons in response to an unknown insult in genetically susceptible individuals, a definite trigger has not been identified. The diagnosis of achalasia is suggested by clinical features and conf irmed by further diagnostic tests, such as esophagogastroduodenoscopy (EGD), manometry or barium swallow. These studies are not only used to exclude pseudoachalasia, but also might help to categorize the disease by severity or clinical subtype. Recent advances in diagnostic methods, including high resolution manometry (HRM), might allow prediction of treatment responses. The primary treatments for achieving long-term symptom relief are surgery and endoscopic methods. Although limited high-quality data exist, it appears that laparoscopic Heller myotomy with partial fundoplication is superior to endoscopic methods in achieving long-term relief of symptoms in the majority of patients. However, the current clinical approach to achalasia will depend not only on patients' characteristics and clinical subtypes of the disease, but also on local expertise and patient preferences.展开更多
基金the National Natural Science Foundation of China, No. C030503039
文摘AIM: To investigate the effects of electroacupuncture (EA) at neiguan (PC6) on gastric distention-induced transient lower esophageal sphincter relaxations (TLESRs) and discuss the mechanisms of this treatment. METHODS: ProtocolⅠ: Twelve healthy cats underwent gastric distention for 60 min on the first day. Electrical acupoint stimulation was applied at the neiguan or a sham point on the hip in randomized order before gastric distention, on the third day and fifth day. Those cats that underwent EA at neiguan on the fifth day were named "Neiguan Group" and the cats that underwent EA at a sham acupoint on the fifth day were named "Sham Group" (control group). During the experiment the frequency of TLESRs and lower esophageal sphincter (LES) pressure were observed by a perfused sleeve assembly. Plasma levels of gastrin (GAS) and motilin (MTL) were determined by radioimmunoassay. Nitrite/nitrate concentration in plasma and tissues were measured by Griess reagent. The nuclei in the brain stem were observed by immunohistochemistry method of c-Fos and NADPH-d dyeing. Protocol Ⅱ: Thirty six healthy cats were divided into 6 groups randomly. We gave saline (2 mL iv. control group), phaclofen (5 mg/kg iv. GABA-B antagonist), cholecystokinin octapeptide (CCK-8) (1 μg/kg per hour iv.), L-Arginine (200 mg/kg iv.), naloxone (2.5 μmol/kg iv.) and tacrine (5.6 mg/kg ip. cholinesterase inhibitor) respectively before EA at Neiguan and gastric distention. And the frequencies of TLESRs in experimental groups were compared with the control group.RESULTS: ProtocolⅠ: Not only the frequency of gastric distention-induced TLESR in 60 min but also the rate of common cavity during TLESRs were significantlydecreased by EA at neiguan compared to that of sham acupoint stimulation. C-Fos immunoreactivity and NOS reactivity in the solitarius (NTS) and dorsal motor nucleus of the vagus (DMV) were significantly decreased by EA at neiguan compared to that of the sham group. However, the positive nuclei of C-Fos and NOS in reticular formation of the medulla (RFM) were increased by EA at neiguan. Protocol Ⅱ: The inhibited effect of EA at neiguan on TLESR’s frequency was completely restored by pretreatment with CCK (23.5/h vs 4.5/h, P < 0.05), L-arginine (17.5/h vs 4.5/h, P < 0.05) and naloxone(12/h vs 4.5/h, P < 0.05). On the contrary, phaclofen (6/h vs 4.5/h, P > 0.05) and tacrine (9.5/h vs 4.5/h, P > 0.05) did not influence it. CONCLUSION: Electric acupoint stimulation at Neiguan significantly inhibits the frequency of TLESR and the rate of common cavity during TLESR in cats. This effect appears to act on the brain stem, and may be mediated through nitric oxide (NO), CCK-A receptor and mu-opioid receptors. But the GABAB receptor and acetylcholine may not be involved in it.
文摘The junction between the esophagus and the stomach is a specialized region, composed of lower esophageal sphincter (LES) and its adjacent anatomical structures, the gastric sling and crural diaphragm. Together these structures work in a coordinated manner to allow ingested food into the stomach while preventing reflux of gastric contents across the esophago-gastric junction (EGJ) into the esophagus. The same zone also permits retrograde passage of air and gastric contents into esophagus during belching and vomiting. The precise coordination required to execute such a complicated task is achieved by a finely-regulated high-pressure zone. This zone keeps the junction between esophagus and stomach continuously closed, but is still able to relax briefly via input from inhibitory neurons that are responsible for its innervation. Alterations of the structure and function of the EGJ and the LES may predispose to gastroesophageal reflux disease (GERD).
基金Supported by Government Foundation Grant from Hebei Provincial Department of Education,No.HBGX2005-52and National Natural Science Foundation of China,No.30371413
文摘AIM: To compare the binding of cholecystokinin (CCK)-8 to CCK receptors in sling and clasp fibers of the human lower esophageal sphincter.
文摘AIM:To investigate the in vitro effects of pantoprazole on rat lower esophageal sphincter(LES)tone.METHODS:Rats weighing 250-300 g,provided by the Yeditepe University Experimental Research Center(Yü-DETAM),were used throughout the study.They were anesthetized before decapitation.LES tissues whose mucosal lining were removed were placed in a stan-dard 30-mL organ bath with a modif ied Krebs solution and continuously aerated with 95% oxygen-5% carbon dioxide gas mixture and kept at room temperature.The tissues were allowed to stabilize for 60 min.Sub-sequently,the contractile response to 10-6 mol/L carba-chol was obtained.Different concentrations of freshly prepared pantoprazole were added directly to the tis-sue bath to generate cumulative concentrations of 5×10-6 mol/L,5×10-5 mol/L,and 1.5×10-4 mol/L.Activi-ties were recorded on an online computer via a 4-channeltransducer data acquisition system using the software BSL PRO v 3.7,which also analyzed the data.RESULTS:Pantoprazole at 5×10-6 mol/L caused a small,but statistically insignif icant,relaxation in the car-bachol-contracted LES(2.23% vs 3.95%).The 5×10-5 mol/L concentration,however,caused a signif icant relax-ation of 10.47% compared with the control.1.5×10-4 mol/L concentration of pantoprazol caused a 19.89% relaxation in the carbachol contracted LES(P<0.001).CONCLUSION:This is the fi rst study to demonstrate that pantoprazole has a relaxing effect in isolated LESs.These results might have signif icant clinical implications for the subset of patients using proton pump inhibitors who do not receive full symptomatic alleviation from gastroesophageal reflux disease.
文摘AIM:To study the relationship between upper esophageal sphincter (UES) relaxation,peristaltic pressure and lower esophageal sphincter (LES) relaxation following deglutition in non-dysphagic subjects.METHODS:Ten non-dysphagic adult subjects had a high-resolution manometry probe passed transnasally and positioned to cover the UES,the esophageal body and the LES.Ten water swallows in each subject were analyzed for time lag between UES relaxation and LES relaxation,LES pressure at time of UES relaxation,duration of LES relaxation,the distance between the transition level (TL) and the LES,time in seconds that the peristaltic wave was before (negative value) or after the TL when the LES became relaxed,and the maximal peristaltic pressure in the body of the esophagus.RESULTS:Relaxation of the LES occurred on average 3.5 s after the bolus had passed the UES and in most cases when the peristaltic wave front had reached the TL.The LES remained relaxed until the peristaltic wave faded away above the LES.CONCLUSION:LES relaxation seemed to be caused by the peristaltic wave pushing the bolus from behind against the LES gate.
文摘AIM: To characterize the effects of age on the mechanisms underlying the common condition of esophageal dysphagia in older patients, using detailed manometric analysis. METHODS: A retrospective case-control audit was performed on 19 patients aged ≥ 80 years (mean age 85 ± 0.7 year) who underwent a manometric study for dysphagia (2004-2009). Data were compared with 19 younger dysphagic patients (32 ± 1.7 years). Detailed manometric analysis performed prospectively included basal lower esophageal sphincter pressure (BLESP), pre-swallow and nadir LESP, esophageal body pressures and peristaltic duration, during water swallows (5 mL) in right lateral (RL) and upright (UR) postures and with solids. Data are mean ± SE; a P-value < 0.05 was considered significant. RESULTS: Elderly dysphagic patients had higher BLESP than younger patients (23.4 ± 3.8 vs 14.9 ± 1.2 mmHg; P < 0.05). Pre-swallow LESP was elevated in the elderly in both postures (RL: 1 and 4 s P = 0.019 and P = 0.05; UR: P < 0.05 and P = 0.05) and solids (P < 0.01). In older patients, LES nadir pressure was higher with liquids (RL: 2.3 ± 0.6 mmHg vs 0.7 ± 0.6 mmHg, P < 0.05; UR: 3.5 ± 0.9 mmHg vs 1.6 ± 0.5 mmHg, P = 0.01) with shorter relaxation after solids (7.9 ± 1.5 s vs 9.7 ± 0.4 s, P = 0.05). No age-related differences were seen in esophageal body pressures or peristalsis duration. CONCLUSION: Basal LES pressure is elevated and swallow-induced relaxation impaired in elderly dysphagic patients. Its contribution to dysphagia and the effects of healthy ageing require further investigation.
基金supported by the National Natural Science Foundation of China[grant numbers 82170577 and 81970479]the Provincial Natural Science Foundation of Guangdong[grant number 2023A1515010187]the Provincial and Municipal Joint Fund Youth Project of Guangdong[grant number 2022A1515111159].
文摘Background:Achalasia is a primary esophageal motility disorder with potential molecular pathogenesis remaining uncertain.This study aimed to identify the differentially expressed proteins and potential pathways among achalasia subtypes and controls to further reveal the molecular pathogenesis of achalasia.Methods:Paired lower esophageal sphincter(LES)muscle and serum samples from 24 achalasia patients were collected.We also collected 10 normal serum samples from healthy controls and 10 normal LES muscle samples from esophageal cancer patients.The 4D label-free proteomic analysis was performed to identify the potential proteins and pathways involved in achalasia.Results:Analysis of Similarities showed distinct proteomic patterns of serum and muscle samples between achalasia patients and controls(both P<0.05).Functional enrichment analysis suggested that these differentially expressed proteins were immunity-,infection-,inflammation-,and neurodegeneration-associated.The mfuzz analysis in LES specimens showed that proteins involved in the extracellular matrix–receptor interaction increased sequentially between the control group,type III,type II,and type I achalasia.Only 26 proteins altered in the same directions in serum and muscle samples.Conclusions:This first 4D label-free proteomic study of achalasia indicated that there were specific protein alterations in both the serum and muscle of achalasia,involving immunity,inflammation,infection,and neurodegeneration pathways.Distinct protein clusters between types I,II,and III revealed the potential molecular pathways associated with different disease stages.Analysis of proteins changed in both muscle and serum samples highlighted the importance of further studies on LES muscle and revealed potential autoantibodies.
基金Supported by the Research Grant Contract Allocated for Basic Research from the Chulalongkorn University,No.HEA663000047.
文摘Gastroesophageal reflux(GER)in children is very common and refers to the involuntary passage of gastric contents into the esophagus.This is often physiological and managed conservatively.In contrast,GER disease(GERD)is a less common pathologic process causing troublesome symptoms,which may need medical management.Apart from abnormal transient relaxations of the lower esophageal sphincter,other factors that play a role in the pathogenesis of GERD include defects in esophageal mucosal defense,impaired esophageal and gastric motility and clearance,as well as anatomical defects of the lower esophageal reflux barrier such as hiatal hernia.The clinical manifestations of GERD in young children are varied and nonspecific prompting the necessity for careful diagnostic evaluation.Management should be targeted to the underlying aetiopathogenesis and to limit complications of GERD.The following review focuses on up-to-date information regarding of the pathogenesis,diagnostic evaluation and management of GERD in children.
基金Supported by The Grants-in-Aid from Science Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, No. 19590724
文摘AIM:To clarify the effects of anti-hypertensive drugs on esophageal contraction and determine their possi-ble relationship with gastro-esophageal reflux disease.METHODS:Thirteen healthy male volunteers were enrolled. Esophageal body peristaltic contractions and lower esophageal sphincter (LES) pressure were measured using high resolution manometry. All subjects were randomly examined on four separate occasions following administrations of nifedipine,losartan,and atenolol,as well as without any drug administration.RESULTS:Peristaltic contractions by the esophageal body were separated into three segments by two troughs. The peak peristaltic pressures in the mid and lower segments of the esophageal body under atenolol administration were signifi cantly higher than those without medication in a supine position. On the other hand,peristaltic pressures under nifedipine administration were lower than those observed without drug ad-ministration. Losartan did not change esophageal body peristalsis. Atenolol elevated LES pressure and slowed peristaltic wave transition,while the effects of nifedip-ine were the opposite. CONCLUSION:Among the anti-hypertensive drugs tested,atenolol enhanced esophageal motor activity,which was in contrast to nifedipine.
文摘Almost 15 years have passed since the first paper on the possibility of using magnets to prevent gastro-esophageal reflux(GER)was published and so it is time to assess the results obtained with the first magnetic device available on the market,the Linx magnetic sphincter augmentation(MSA)and to consider what other options are forthcoming.MSA demonstrated an anti-reflux activity similar to that of Nissen fundoplication,considered the“gold standard”surgical treatment for GER disease,and caused less gas-bloating and a better ability to allow vomiting and belching.However,unlike Nissen fundoplication,this magnetic device is burdened by complications,which are roughly similar to those of the non-magnetic anti-reflux Angelchik prosthesis,that,after considerable use in the eighties,was shelved due to these complications.It is interesting to note that some of these complications show the same pathophysiological mechanism in both devices.The upcoming new magnetic devices should avoid these complications,as their anti-reflux magnetic mechanism is completely different.The experiments in animals regarding these new magnetic appliances were examined,remarking their advantages and drawbacks,but the way to apply them in surgical practice is long and difficult,although worthy,as they represent the future of magnetic surgery.
文摘Objectives: In this retrospective analysis, we explored the effect of botulinum toxin A (BTA) injection to treat oropharyngeal dysphagia or esophageal dysfunction caused by diseases of the upper (UES) and lower (LES) esophageal sphincter. Methods: In total, 48 patients (17 patients with UES disorders, and 31 patients with LES dysfunction;mean age 64 years) were treated between 1996 and 2007 in our hospital. Comorbid diseases as well as maintenance medication were documented to evaluate the overall health status of our patients. The mean duration of symptoms, the number of pre-treatments and the specification of dysphagia were considered. Results: One month after injection, the response rates were 73.3% (UES group) and 76.6% (LES group). Most patients in the UES group received 30-40 units BTA (Botox?) whereas most patients in the LES group were treated with 100 units BTA. In cases of re-injection, 50% of patients in the UES group experienced an escalation of dosage (up to 75 units), whereas the other 50% received the same dosage. The dosages in the LES group were mostly kept constant. Conclusion: Comparing the two groups with esophageal dysfunction of fundamentally different etiologies (UES/LES), a discrepancy in the level of symptom relief, onset and a longer cessation of clinical benefit were observed in the LES group. In this analysis, we were able to show that injection of BTA is an effective and safe treatment for disorders of the UES and LES.
文摘Idiopathic achalasia is a rare primary motility disorder of the esophagus. The classical features are incomplete relaxation of a frequently hypertensive lower esophageal sphincter (LES) and a lack of peristalsis in the tubular esophagus. These motor abnormalities lead to dysphagia, stasis, regurgitation, weight loss, or secondary respiratory complications. Although major strides have been made in understanding the pathogenesis of this rare disorder, including a probable autoimmune mediated destruction of inhibitory neurons in response to an unknown insult in genetically susceptible individuals, a definite trigger has not been identified. The diagnosis of achalasia is suggested by clinical features and conf irmed by further diagnostic tests, such as esophagogastroduodenoscopy (EGD), manometry or barium swallow. These studies are not only used to exclude pseudoachalasia, but also might help to categorize the disease by severity or clinical subtype. Recent advances in diagnostic methods, including high resolution manometry (HRM), might allow prediction of treatment responses. The primary treatments for achieving long-term symptom relief are surgery and endoscopic methods. Although limited high-quality data exist, it appears that laparoscopic Heller myotomy with partial fundoplication is superior to endoscopic methods in achieving long-term relief of symptoms in the majority of patients. However, the current clinical approach to achalasia will depend not only on patients' characteristics and clinical subtypes of the disease, but also on local expertise and patient preferences.