Segmental characteristics of oesophageal peristalsis in paediatric patients.

High-resolution manometry (HRM) in adults identifies a sequential chain of pressure segments that together form normal oesophageal peristalsis. HRM was performed in 40 neonates, infants/toddlers and children (age 1 day-14 years) to see if a similar segmental pattern could be identified in paediatric subjects. A chain of three pressure segments was found with inter-segmental troughs at 27.4 +/- 1.1%, 62.6 +/- 1.3% and 94.9 +/- 0.8% oesophageal length. The first and second pressure troughs were similarly distributed along the oesophagus across age groups; the third was 7.6-8.9% oesophageal length further from the lower oesophageal sphincter in neonates (P < 0.05 compared with other age groups). There were no significant differences in trough locations between subjects with or without oesophageal disease, controlling for age. Consistent presence of all three segments was less common in neonates, primarily because of fewer swallows demonstrating the first (proximal) and third (distal) segments compared with children. HRM in paediatric patients demonstrates, from neonates to children, the distinctive chain of pressure events that also characterizes oesophageal peristalsis in adults. The segmental character to oesophageal peristalsis should be taken into consideration in manometric investigation of all age groups - for example, in testing pharmacological responses and evaluating clearance mechanisms.

Influence of spastic motor disorders of the esophageal body on outcomes from laparoscopic antireflux surgery.

BACKGROUND: The clinical outcomes of laparoscopic antireflux surgery (LARS) in patients with the spectrum of nonspecific spastic esophageal motor disorders (NSSDs) are not known. METHODS: From a prospective database of patients undergoing LARS between 1997 and 2000, those with preoperative manometry at our institution and follow-up at ?6 months were identified. RESULTS: Of the 121 patients, 35 had NSSDs. There were no differences in symptoms between groups preoperatively, but in the immediate postoperative period NSSD patients had more symptoms than nonspastic patients. At 18-month mean follow-up, NSSD patients reported significantly more heartburn (22% vs 7%), waterbrash (14% vs 4%), and medication usage (17% vs 5%) than nonspastic patients (p <0.05 for each). Despite this difference, nearly all patients reported subjective improvement postoperatively, and the degree of improvement was similar between groups. CONCLUSIONS: Patients with NSSDs are more likely to have esophageal symptoms following LARS than subjects without these abnormalities. However, these patients still experience significant improvement in preoperative symptoms.

Association of depression and diabetes complications: a meta-analysis.

OBJECTIVE: The objective of this study was to examine the strength and consistency of the relationship between depression and diabetes complications in studies of type 1 and type 2 adult patients with diabetes. METHOD: MEDLINE and PsycINFO databases were searched for articles examining depression and diabetes complications in type 1 and type 2 diabetes samples published between 1975 and 1999. Meta-analytic procedures were used. Studies were reviewed for diabetes type, sample size, statistical tests, and measures of diabetes complications and depression. Significance values, weighted effect sizes r, 95% confidence intervals (CI), and tests of homogeneity of variance were calculated for the overall sample (k = 27) and for subsets of interest. RESULTS: A total of 27 studies (total combined N = 5374) met the inclusion criteria. A significant association was found between depression and complications of diabetes (p < .00001, z = 5.94). A moderate and significant weighted effect size (r = 0.25; 95% CI: 0.22-0.28) was calculated for all studies reporting sufficient data (k = 22). Depression was significantly associated with a variety of diabetes complications (diabetic retinopathy, nephropathy, neuropathy, macrovascular complications, and sexual dysfunction). Effect sizes were in the small to moderate range (r = 0.17 to 0.32). CONCLUSIONS: These findings demonstrate a significant and consistent association of diabetes complications and depressive symptoms. Prospective, longitudinal studies are needed to identify the pathways that mediate this association.

The association of irritable bowel syndrome and somatization disorder.

BACKGROUND AND OBJECTIVE: Irritable bowel syndrome (IBS) and somatization disorder (SD) are defined by nonobjective symptoms that overlap considerably. Psychiatric symptoms associated with IBS may originate from SD in IBS patients. Previous studies of IBS have not considered SD separately from IBS. METHODS: This study explored psychiatric symptoms and illness behavior in IBS in relation to SD. A total of 50 outpatients with IBS or ulcerative colitis (UC) were evaluated with the Diagnostic Interview Schedule and Illness Behavior Questionnaire. RESULTS: Definite or probable SD was diagnosed in no UC patients and in 42% of IBS patients (confirmed in 25% and lacking one symptom in another 17%). IBS patients with probable or definite SD, but not those without SD, reported more psychiatric symptoms and abnormal illness behaviors than did UC patients. SD accounted for the association of psychiatric symptoms with IBS. CONCLUSIONS: In this university-based office setting, the association of psychiatric features with IBS appears heterogeneous predicated on whether SD is present. Future studies of functional bowel diseases should distinguish between patients with and without SD to clarify its relationship to these disorders. Clinicians should consider whether patients with functional disorders have SD, a diagnosis that indicates specific clinical management strategies.

The prevalence of comorbid depression in adults with diabetes: a meta-analysis.

OBJECTIVE: To estimate the odds and prevalence of clinically relevant depression in adults with type 1 or type 2 diabetes. Depression is associated with hyperglycemia and an increased risk for diabetic complications; relief of depression is associated with improved glycemic control. A more accurate estimate of depression prevalence than what is currently available is needed to gauge the potential impact of depression management in diabetes. RESEARCH DESIGN AND METHODS: MEDLINE and PsycINFO databases and published references were used to identify studies that reported the prevalence of depression in diabetes. Prevalence was calculated as an aggregate mean weighted by the combined number of subjects in the included studies. We used chi(2) statistics and odds ratios (ORs) to assess the rate and likelihood of depression as a function of type of diabetes, sex, subject source, depression assessment method, and study design. RESULTS: A total of 42 eligible studies were identified; 20 (48%) included a nondiabetic comparison group. In the controlled studies, the odds of depression in the diabetic group were twice that of the nondiabetic comparison group (OR = 2.0, 95% CI 1.8-2.2) and did not differ by sex, type of diabetes, subject source, or assessment method. The prevalence of comorbid depression was significantly higher in diabetic women (28%) than in diabetic men (18%), in uncontrolled (30%) than in controlled studies (21%), in clinical (32%) than in community (20%) samples, and when assessed by self-report questionnaires (31%) than by standardized diagnostic interviews (11%). CONCLUSIONS: The presence of diabetes doubles the odds of comorbid depression. Prevalence estimates are affected by several clinical and methodological variables that do not affect the stability of the ORs.

Similarities in cyclic vomiting syndrome across age groups.

OBJECTIVE: Cyclic vomiting syndrome is well recognized in children yet has poorly defined pathogenesis and treatment. Cyclic vomiting syndrome is occasionally diagnosed in older subjects, but little attempt has been made to determine if such cases represent a unique disorder. METHODS: We reviewed clinical data from 39 patients aged 1.8-75 yr with cyclic vomiting syndrome meeting published criteria for diagnosis. Clinical characteristics were compared between subjects with symptom onset in childhood (<12 yr, n = 18) and subjects with onset at an older age (> or =12 yr, n = 21; mean age at onset 34.8+/-3.8 yr). RESULTS: All patients had stereotypical episodes of vomiting separated by varying symptom-free intervals. The prevalence rates of prodromal symptoms, triggering events, alleviants, associated symptoms including abdominal pain and diarrhea, and past or family history of migraine were similar in the children and older subjects with the syndrome (p > 0.3 for each). Delay in diagnosis was greater in the older subset (3.1+/-0.8 yr vs 7.9+/-3.1 yr, p < 0.05). Interepisode intervals and total number of hospitalizations did not differ significantly between younger and older patients, but duration of episodes was significantly longer in the older group (2.0+/-0.5 days vs 3.8+/-0.4 days, p < 0.01). When subjects were further substratified by age of illness onset, duration of episodes progressively increased from infant/toddlers (1.8+/-0.4 days) through childhood (2.3+/-0.5 days) and adolescence (2.9+/-1.0 days) and into adulthood (3.9+/-0.5; p < 0.05 across groups). Episode duration did not lengthen further in subgroups >20 yr of age. CONCLUSIONS: Many characteristics of cyclic vomiting syndrome are similar irrespective of age at disorder onset, suggesting a uniform pathogenesis. Duration of episodes increases with age to age 20 yr. Increased awareness of the condition and a high index of suspicion may help decrease delay in diagnosis after symptom onset.

Detection of incomplete lower esophageal sphincter relaxation with conventional point-pressure sensors.

OBJECTIVE: Completeness of lower esophageal sphincter relaxation, a parameter used to establish the diagnosis of achalasia, is an important manometric determination. This study compared four analysis methods that use point-pressure measurements to determine their relative accuracy and the best threshold values for incomplete relaxation. METHODS: Analyses were performed on 153 manometric studies that employed a 21-lumen catheter with pressure recording sites spaced at 1-cm intervals. Lower sphincter relaxation was measured from most appropriate sites as the 1) lowest residual pressure within 5 s of swallowing, 2) lowest residual pressure across the entire postdeglutitive period, 3) lowest mean residual pressure over a floating 3-s interval after swallowing, and 4) mean transsphincteric esophagogastric gradient extracted from a combination of conventional and topographic manometric information. Intragastric baseline pressures were taken both from the pull-through maneuver and from concurrent intragastric recordings, and methods were compared by their receiver operating characteristics. RESULTS: Best threshold values for segregating achalasia from nonachalasic controls differed across methods and depended on presence or absence of peristalsis in the comparison group. Transsphincteric gradient measurement had high sensitivity (> or = 0.94) and specificity (> or = 0.98) for achalasia irrespective of comparison group and was superior to all other methods. The 3-s mean residual pressure demonstrated greatest discriminant capabilities of the remaining conventional methods, which were modestly improved with concurrent measurement of intragastric pressure. CONCLUSIONS: Analyses that average postdeglutitive pressures are superior to isolated nadir values in correctly discerning incomplete lower sphincter relaxation. The transsphincteric gradient is a novel approach for measuring sphincter relaxation, is unaffected by sphincter asymmetry and axial movement, and has the best receiver operating characteristics using point-pressure sensors.

Esophageal motor disorders.

Esophageal motor function remains of investigative and clinical interest because of its relevance to symptoms and its relation to the occurrence and management of gastroesophageal reflux disease. Refinement in diagnostic methods continues to occur, and improved tests for identifying the nature or severity of motor disturbances in both the proximal and distal esophageal regions are now well described. Controversy concerning the management of achalasia, the best-understood distal motor disorder, is resolving as the benefits and disadvantages of available treatment options are becoming recognized. The relation of esophageal motor dysfunction to outcomes from antireflux surgery remains incompletely understood.

Topographic esophageal manometry: an emerging clinical and investigative approach.

Topographic esophageal manometry utilizes an increased number of pressure sensors and three-dimensional displays to fully reveal the pressure continuum representing peristalsis. The techniques demonstrate that peristalsis is comprised of a chain of pressure segments, beginning at the upper esophageal sphincter and continuing through lower sphincter aftercontraction. Topographic methods have already proven useful in both research and clinical settings. Description of the techniques, the topographic representation of normal and abnormal esophageal motility, and advantages of topography over conventional manometric methods are discussed in this review.

Application of topographical methods to clinical esophageal manometry.

OBJECTIVE: Topographical manometric methods have improved the understanding of esophageal peristalsis in research applications but require a large number of recording sensors. Commonly used methods limited to four sensors were compared to topographical methods to determine whether the latter also had significant clinical utility. METHODS: Two hundred twelve patients referred for esophageal manometry were studied with a data acquisition system having 21 intraluminal recording sites, and the findings were analyzed independently using both limited (pull-through plus four recording sites) and topographical approaches (all sites). Discrepant results were clarified using supportive clinical data. RESULTS: The two methods were in diagnostic agreement in 187 cases (88.2%). Topographical methods correctly identified all 26 patients with achalasia within the group with aperistalsis (n = 36). The limited methods could not confidently identify six achalasia patients and were significantly less effective in segregating aperistaltic disorders (p < 0.05 across methods). Topographical methods alone detected evidence of incomplete lower esophageal sphincter relaxation in 12 additional patients, eight of whom had clinical data supporting the findings. Topographical methods identified the upper margin of the lower sphincter in all but three subjects (1.4%); limited methods could not identify this location in these and five additional subjects (3.8%) and differed from the topographical measurement by > or = 2 cm in 11.9% of cases. CONCLUSIONS: Topographical methods are more accurate than commonly used methods in diagnosing the type of severe motor dysfunction and provide additional information important in the clinical practice of esophageal manometry.

Depression and poor glycemic control: a meta-analytic review of the literature.

OBJECTIVE: Depression is common among patients with diabetes, but its relationship to glycemic control has not been systematically reviewed. Our objective was to determine whether depression is associated with poor glycemic control. RESEARCH DESIGN AND METHODS: Medline and PsycINFO databases and published reference lists were used to identify studies that measured the association of depression with glycemic control. Meta-analytic procedures were used to convert the findings to a common metric, calculate effect sizes (ESs), and statistically analyze the collective data. RESULTS: A total of 24 studies satisfied the inclusion and exclusion criteria for the meta-analysis. Depression was significantly associated with hyperglycemia (Z = 5.4, P < 0.0001). The standardized ES was in the small-to-moderate range (0.17) and was consistent, as the 95% CI was narrow (0.13-0.21). The ES was similar in studies of either type 1 or type 2 diabetes (ES 0.19 vs. 0.16) and larger when standardized interviews and diagnostic criteria rather than self-report questionnaires were used to assess depression (ES 0.28 vs. 0.15). CONCLUSIONS: Depression is associated with hyperglycemia in patients with type 1 or type 2 diabetes. Additional studies are needed to establish the directional nature of this relationship and to determine the effects of depression treatment on glycemic control and the long-term course of diabetes.

Fluoxetine for depression in diabetes: a randomized double-blind placebo-controlled trial.

OBJECTIVE: Depression is prevalent in patients with diabetes. It is associated with poor glycemic control and is linked to an increased risk for diabetic complications. In this study, we assessed the efficacy of fluoxetine for depression in patients with diabetes. RESEARCH DESIGN AND METHODS: Sixty patients with diabetes (type 1, n = 26; type 2, n = 34) and major depressive disorder entered an 8-week randomized placebo-controlled double-blind trial. Patients were given daily doses of fluoxetine (up to 40 mg/day). The Beck Depression Inventory (BDI) and Hamilton Rating Scale for Depression (HAMD) were used to measure the severity of depression and to determine the percentage of patients who achieved substantial improvement or complete remission. GHb levels were obtained to monitor glycemic control. RESULTS: Reduction in depression symptoms was significantly greater in patients treated with fluoxetine compared with those receiving placebo (BDI, -14.0 vs. -8.8, P = 0.03; HAMD, -10.7 vs. -5.2, P = 0.01). The percentage of patients achieving a significant improvement in depression per the BDI was also higher in the fluoxetine group (66.7 vs. 37.0%, P = 0.03). Additionally, trends toward a greater rate of depression remission (48.1 vs. 25.9%, P = 0.09 per the HAMD) and greater reduction in GHb (-0.40 vs. -0.07%, P = 0.13) were observed in the fluoxetine group. CONCLUSIONS: Fluoxetine effectively reduces the severity of depression in diabetic patients. Our study demonstrated that after only 8 weeks, this treatment also produced a trend toward better glycemic control.

Persistence of abnormal gastrointestinal motility after operation for Hirschsprung's disease.

OBJECTIVE: Recent studies in patients with Hirschsprung's disease (HD) suggest that morphological abnormalities of the intramural intestinal plexuses are not restricted to the colon. In this report, symptoms and objective tests of gastrointestinal (GI) motor dysfunction were determined long after operative treatment to see whether evidence of a more widespread and relevant motility disturbance could be detected. METHODS: Twenty-one children were available for study an average of 6.6 yr after surgery for HD. All of these patients underwent evaluation of bowel frequency per week, total GI transit time (TGTT), and a scintigraphic gastric emptying test using solid food; anorectal manometry and segmental colonic transit times were performed in a subset of patients. Results were compared with findings in appropriately matched controls. RESULTS: Frequency of defecation per week in patients with HD after surgery was not different from that in control children, but TGTT was significantly longer (p < 0.01). Percentage retention of gastric isotope at 60 min exceeded the normal range in 12 of 21 (57.1%) patients, and colonic transit was abnormal in all six children studied. Symptoms persisted in two-thirds of patients postoperatively, and transit abnormalities were more common in the symptomatic subset (p = 0.026). CONCLUSIONS: Our data show that, in a subset of patients with HD, GI motor dysfunction persists long after surgical correction. The heterogeny of basic defects responsible for HD could provide the substrate for these motor abnormalities that, in turn, seem at least partially responsible for continuation of the symptomatic state.

Topographic analysis of esophageal double-peaked waves.

BACKGROUND & AIMS: Esophageal double-peaked waves occur with increased frequency in patients with functional esophageal symptoms. This study was undertaken to further understand the mechanisms responsible for their production. METHODS: Topographic methods that consider temporal and spatial relationships of pressure data were used to examine 74 double-peaked waves detected in 18 subjects referred for manometric evaluation of unexplained symptoms. The studies were performed with a computerized data acquisition and analysis system designed for topographic plotting. RESULTS: The second peak appeared to represent muscle contraction that merged with an unusually strong pressure site in the third topographic segment and covered 6.3 +/- 1.6 cm (33.5% +/- 8.5% esophageal length) proximal to this site. In 50 swallows (67.6%), the peak itself progressed in a retrograde direction at 13.2 +/- 10.8 cm/s, suggesting cephalad extension of a strong distal motor event. Analysis of wave onsets and movement of the peristaltic trailing edge detected retrograde propagation in up to 33.8% of waves, antegrade propagation in 2.7%, and simultaneous contraction in the remainder. CONCLUSIONS: In symptomatic patients, the second peak in a double-peaked wave is typically a short, simultaneous, or retrograde pressure event in the region of and merging with the third topographic segment in the distal esophageal body. Topographic methods help explain the common association of these waveforms with other features of exaggerated contraction in the distal esophagus and suggest their relationship to inadequate inhibitory nerve function.

Esophageal motor disorders.

Motor dysfunction is responsible for symptomatic illnesses both in the proximal skeletal muscle region and in the distal smooth muscle esophagus. Practical methods for diagnosing and treating oropharyngeal dysphagia continue to reach consensus. Achalasia, the most significant of the distal motor disorders, is of investigative interest because of the expanded armamentarium of treatment options. Minimally invasive surgical methods have taken an important foothold as a primary treatment of this disorder. Appreciation is growing for sensory dysfunction that accompanies distal motor disorders. Such dysfunction may help explain the observed discrepancies between symptoms and measurable motility abnormality.

Cyclic vomiting syndrome in adults: clinical features and response to tricyclic antidepressants.

OBJECTIVE: Cyclic vomiting syndrome (CVS) has been described infrequently in adults, and treatment in both children and adults remains unsatisfactory. We report clinical features of a group of adults with CVS and anecdotal outcome from open-label treatment with tricyclic antidepressants, medications that have some efficacy in other unexplained gastrointestinal disorders. METHODS: Clinical data were examined from 17 adult patients with CVS seen over a 10-yr period, each having been treated with a tricyclic antidepressant. Outpatient records were reviewed, clinical outcome was extracted using a priori criteria, and findings were compared with 37 patients having usual functional nausea and vomiting who also received tricyclic antidepressant therapy. RESULTS: Symptoms in CVS began at age 35 yr (range 14-73 yr); the average episode length was 6 days (range 1-21 days) and the symptom-free interval averaged 3.1 months (range 0.5-6 months). Vomiting cycles typically began without warning, and fewer than one-third of the subjects reported a prodrome or potential trigger event, such as menstrual periods, pregnancy, or large meals. Sleep was seemingly beneficial in 23.5%. Tricyclic antidepressant therapy was associated with complete remission in 17.6% and partial response in 58.8%, but was less effective than for functional nausea and vomiting (p = 0.02). CONCLUSIONS: CVS is a rare diagnosis with distinctive features in adults. Duration of episodes and cycles varies considerably across subjects. In open-label, uncontrolled use, tricyclic antidepressants appear beneficial for some subjects but are less effective in CVS than in chronic, persistent functional nausea and vomiting.