Medical and surgical management of esophageal and gastric motor dysfunction

he occurrence of esophageal and gastric motor dysfunctions happens, when the software of the esophagus and the stomach is injured. This is really a program previously established in the enteric nervous system as a constituent of the newly called neurogastroenterology. The enteric nervous system is composed of small aggregations of nerve cells, enteric ganglia, the neural connections between these ganglia, and nerve fibers that supply effectors tissues, including the muscle of the gut wall. The wide range of enteric neuropathies that includes esophageal achalasia and gastroparesis highlights the importance of the enteric nervous system. A classification of functional gastrointestinal disorders based on symptoms has received attention. However, a classification based solely in symptoms and consensus may lack an integral approach of disease. As an alternative to the Rome classification, an international working team in Bangkok presented a classification of motility disorders as a physiology-based diagnosis. Besides, the Chicago Classification of esophageal motility was developed to facilitate the interpretation of clinical high-resolution esophageal pressure topography studies. This review covers exclusively the medical and surgical management of the esophageal and gastric motor dysfunction using evidence from well-designed studies. Motor control of the esophagus and the stomach, motor esophageal and gastric alterations, treatment failure, side effects of PPIs, overlap of gastrointestinal symptoms, predictors of treatment, burden of GERD medical management, data related to conservative treatment vs. antireflux surgery, and postsurgical esophagus and gastric motor dysfunction are also taken into account.     

Prospective evaluation of medication-induced esophageal injury and its relation to esophageal function.

BACKGROUND: Few prospective studies are available on the incidence of medication-induced esophageal injury (MIEI). AIMS: To prospectively study the occurrence of MIEI with indomethacin and doxycycline and the predictive factors for its development. METHODS: In an operator-blinded study, 51 patients (age 16-65 y) requiring indomethacin (n = 24) or doxycycline (27) underwent symptom evaluation, endoscopy and scintigraphy before and after 7 days of therapy. MIEI was defined as de novo occurrence or worsening of pre-existing esophagitis or development of esophageal ulcer. RESULTS: Pre-therapy endoscopy was normal in 32 patients and revealed esophagitis in 19 (grade I--11, grade II--8). Post-therapy, 16 patients developed esophageal symptoms, which appeared earlier with doxycycline (2.0 [0.8] vs 4.1 [1.7] days, p = 0.016). MIEI developed in 23 patients--de novo esophagitis in 16, worsening of esophagitis in 6; 5 patients developed ulcer. Seven of 12 patients with hiatus hernia developed MIEI. Presence of pre-therapy gastroesophageal reflux disease did not predict MIEI. There was no difference in pre- or post-therapy transit values between patients with and without MIEI; patients who developed ulcers had significantly slower esophageal transit (p < 0.05). There was no difference in esophageal transit or occurrence of MIEI between patients who received indomethacin or doxycycline; however, 5 of 8 patients with hiatus hernia who received doxycycline developed MIEI (p = 0.02; relative risk 3.96 [CI 1.2-12.7]). CONCLUSIONS: 40% of patients receiving doxycycline or indomethacin developed MIEI; 10% developed ulcers. Hiatus hernia increased the risk for MIEI.     

Prospective evaluation of high-dose bethanechol in investigation of esophageal chest pain

We compared the value of bethanechol 80 g/kg subcutaneously, acid infusion with a 0.1 normal hydrochloric acid, and edrophonium 80 g/kg intravenously as provocative agents to reproduce chest pain and manometric alterations in 72 patients with noncardiac chest pain. No patient developed typical chest pain and manometric alteration with acid infusion, while five (6.9%) patients developed these changes with edrophonium and four (5.6%) with bethanechol. Only one patient developed diagnostic changes exclusively with bethanechol. All patients tested with bethanechol developed some degree of local pain or significant cholinergic symptoms, with two patients requiring atropine for relief. Side effects from edrophonium were infrequent (28% of patients tested) and did not require atropine administration. We conclude that, using the parameters of typical chest pain and the development of manometric alterations as proof of the esophageal origin of chest pain, bethanechol at 80 g/kg adds little information beyond that obtainable with edrophonium. Further, the high incidence of bethanechol-related side effects at 80 g/kg suggests that this dose should not be generally recommended.     

Functional chest pain of esophageal origin: hyperalgesia or motor dysfunction

OBJECTIVE: Many patients with functional (noncardiac) chest pain exhibit both hypersensitivity and motor dysfunction of the esophageal wall. We aimed to determine whether the sensory or motor dysfunction plays an important role in the pathogenesis of chest pain. METHODS: We performed graded balloon distentions of the esophagus using impedance planimetry in 16 consecutive patients with chest pain and otherwise normal cardiac and esophageal evaluations and in 13 healthy controls. In those patients who experienced chest pain with balloon distention, the test was repeated after atropine was given. Sensory and biomechanical parameters were measured. RESULTS: Balloon distention reproduced typical chest pain in 13/16 patients (81%) and at lower (p < 0.01) sensory thresholds than controls. Pain was reproduced in all 13 patients and at lower (p < 0.05) sensory thresholds after atropine. Also, after atropine, the esophageal cross-sectional area and wall tension increased (p < 0.05), the tension/strain association shifted to the right (p < 0.05), and reactivity decreased (p < 0.002) relative to results before atropine or in healthy controls (i.e., the esophageal wall relaxed and became more deformable). CONCLUSIONS: Even after relaxing the esophageal wall, most patients experienced chest pain and at lower sensory thresholds. Hence, hyperalgesia rather than motor dysfunction appears to be the predominant mechanism for functional chest pain of esophageal origin.     

Prospective evaluation of autonomic dysfunction in aggressive management of diabetic microangiopathy

Twenty-six type I diabetic nephropathy patients in a rigorous schedule for glucose control to preserve kidney function were studied to determine autonomic functional changes during 18 months. Intercurrent and nonrelated acute illness, withdrawal from the study for personal reasons, or failure to undergo testing on schedule resulted in complete data at 1 year for 26 of the original 41 patients enrolled, 24 patients completing a further 6 months. Glycohemoglobin A1c dropped for the total group from 9.0 to 7.9 at 6 months, 8.0 at 12 months, and 8.1 at 18 months (P < .01).Autonomic function tests revealed baseline results that were below the anticipated normals for age in 38% to 56% of patients. Timed ventilatory heart rate variations measured for the total group were 1.11, 1.13, 1.10, and 1.09 (normal ≥1.20). Valsalva heart rate variations for the total group were 1.27, 1.30, 1.255, and 1.35 (normal ≥1.50). Assumption of upright posture-related heart rate variations for the total group were 1.10, 1.07, 1.07, and 1.06 (normal ≥1.20). Mean arterial pressure day/night ratios for the total group were 1.04, 1.05, 1.05, and 1.08 (normal ≥1.10). Group analysis based on differences in insulin treatment programs, levels of blood pressure, and levels of renal function revealed no significant differences from the total group or companion groups during 18 months. Patients with a glycohemoglobin A1c of <8.0% were more likely to normalize mean arterial pressure day/night ratios than those with glycohemoglobin A1c ≥8.0%.We conclude that aggressive glucose control in diabetic patients with proteinuria for a period of 18 months resulted in a reproducible pattern of autonomic function tests during that period of time with neither worsening nor improvement. The restoration of day/night mean arterial pressure variation in a minority of patients should be studied with a larger cohort.     

Down's syndrome

The sequencing of chromosome 21 and the use of models of Down's syndrome in mice have allowed us to relate genes and sets of genes to the neuropathogenesis of this syndrome, and to better understand its phenotype. Research in prenatal screening and diagnosis aims to find methods to identify fetuses with Down's syndrome, and reduce or eliminate the need for amniocentesis. Other areas of active research and clinical interest include the association of Down's syndrome with coeliac disease and Alzheimer's disease, and improved median age of death. Medical management of the syndrome requires an organised approach of assessment, monitoring, prevention, and vigilance. Improvements in quality of life of individuals with Down's syndrome have resulted from improvements in medical care, identification and treatment of psychiatric disorders (such as depression, disruptive behaviour disorders, and autism), and early educational interventions with support in typical educational settings. Approaches and outcomes differ throughout the world.     

Pathophysiology of gastroesophageal reflux diseases in Chinese--role of transient lower esophageal sphincter relaxation and esophageal motor dysfunction

BACKGROUND AND AIMS: Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism for gastroesophageal reflux in the Western population. The major reflux mechanism in Chinese patients with GERD has not been studied before. METHODS: Fifty-four patients with GERD and 28 controls underwent stationary baseline manometry and the 24-h ambulatory esophageal pH monitoring. TLESRs were measured before and after an 850 kcal meal in the supine position. Primary peristalsis, secondary peristalsis, and esophageal acid clearance were measured by esophageal manometry. RESULTS: Total time esophageal pH 相似文献   

Dysphagia and esophageal motor dysfunction in gastroesophageal reflux are corrected by fundoplication

Abnormalities in esophageal peristaltic function and acid clearance appear to be responsible for prolonged esophageal acid exposure, a major determinant of the reflux esophagitis and esophageal stricture. We evaluated esophageal motility by manometry in 50 healthy controls and in 35 symptomatic reflux patients before, within 6 months, and 1 year after Nissen fundoplication. Preoperative motility was analyzed in relation to the presence or absence of both nonobstructive dysphagia and erosive esophagitis. We found that (a) preoperative dysphagia was related more to peristaltic dysfunction than to esophagitis; (b) peristaltic wave amplitude and duration were significantly lower than control values in patients with reflux, without correlation to degree of esophagitis or lower esophageal sphincter hypotension; (c) dysphagia ceased in most patients after antireflux surgery at the same time that normal motility was restored independently of lower esophageal sphincter pressure increments. These results suggest that motility disturbances are an important cause of dysphagia in reflux disease, and that reflux is the cause of, rather than the consequence of, peristaltic dysfunction.     

Arthropathy of Down's syndrome

Down's syndrome (trisomy 21) is associated with a variety of skeletal abnormalities and an increased incidence of joint hypermobility. Children with Down's syndrome are known to have a number of immunologic abnormalities and an increased incidence of autoimmune phenomena. We report 7 patients with Down's syndrome and arthritis. Four children had polyarticular disease and 3 had pauciarticular disease at onset. Only 1 child had significant cardiac disease. HLA typing in 5 children did not show specific correlations. Mean duration of followup was 3 years and 7 months. All children responded to nonsteroidal antiinflammatory drugs, but only 1 child is in clinical remission. Two children have died: 1 secondary to cervical spine instability and the other secondary to cardiac compromise. Arthropathy associated with Down's syndrome should be an additional exclusion for the diagnosis of juvenile rheumatoid arthritis. Further investigation of this association may give clues to the relationship between genetic and immunologic factors in the pathogenesis of joint inflammation.     

Insulin secretion in Down's syndrome

Summary Insulin secretion after oral (100 g) and i.v. glucose (0.33 g/kg b.w.) was studied in 14 patients with 21-trisomy (Down's syndrome) and in 18 normal subjects. Plasma immunoreactive insulin (IRI), fasting and at predetermined time intervals during each glucose load, was measured by a double antibody method (Hales-Randle). Tolerance to oral glucose in Down's patients was found to be normal though a flat, late peaked glycaemic response was characteristic of the group. Fasting IRI and insulin levels after oral glucose in patients did not significantly differ from those in the normal group. After i.v. glucose, the patients showed a slower decline of the blood sugar, maintaining significantly higher levels than the normals at 30, 40, 50 and 60 min after the glucose load. However, the peripheral glucose uptake expressed by the K index (Conard) did not significantly differ from the normal despite the lower K values in the patients. Insulin release after i.v. glucose showed some differences between both groups. — The present study cannot support a causal relationship between D.M. and the 21-trisomy through an altered insulin secretion.     

急性呼吸窘迫综合征与多器官功能障碍综合征肺启动机制

多器官功能障碍综合征(MODS)的肺启动机制是指原发肺损伤诱发或启动其它肺外器官的功能障碍或衰竭,该启动机制尚处于学说或假说阶段,尚未得到完全证实.急性呼吸窘迫综合征(ARDS)是全身炎症反应在肺部的失控,是以进行性呼吸困难和顽固性低氧血症为临床表现、具有全身炎症反应综合征(SIRS)特征的呼吸系统危重症.该文从缺氧和SIRS这两个角度评价ARDS在MODS肺启动机制中的作用.     

Hematological changes in Down's syndrome

The many hematological abnormalities observed in patients with Down's syndrome have intrigued hematologists for many years. This review summarizes recent studies concerning the hematological findings in newborn infants with Down's syndrome, the transient leukemoid/leukemia-like proliferative disorders in these infants, the increased incidence of leukemia and types of leukemia in patients with Down's syndrome, and immunological studies of these patients. In addition, studies concerning the significance of the extra genetic material in chromosome 21 found in patients with Down's syndrome are discussed. It appears that the extra genetic material in chromosome 21 confers a proliferative advantage to hematopoietic stem cells, and may make them more prone to further karyotypic changes leading to leukemia. Megakaryocytic proliferative disorders are more common in patients with Down's syndrome. The spectrum of myeloproliferative disorders including myelofibrosis, myeloid metaplasia, and megakaryoblastic leukemia is seen in these patients. Studies of the genetic loci on chromosome 21 have demonstrated loci for enzymes involved in purine biosyntheses. Further studies of specific loci on chromosome 21 may help explain the hematopoietic growth advantages found in the stem cells with an extra chromosome 21.     

Screening for Down's syndrome

Down's syndrome (DS) is the commonest single cause of severe mental retardation in children. It can be diagnosed antenatally by chorionic villus sampling (CVS) or amniocentesis followed by karyotyping. At one time the sole indication for these invasive procedures was maternal age: typically women above age 35. However, this led to the detection of only some 30% of cases of DS at best. In the past ten years a series of biochemical and other abnormalities have been noted in Down's pregnancies and these form the basis for new screening programmes. The most familiar of the biochemical abnormalities are elevated levels of maternal serum human chorionic gonadotrophin (hCG), and reduced levels of α-fetoprotein (AFP) and oestriol (E₃). Changes are also noted in a number of other fetoplacental products. The underlying mechanism of these changes is unknown: suggestions include the possibility that a Down's syndrome pregnancy is relatively 'immature', or that there is a fetal–placental imbalance.