High-resolution manometry in patients with idiopathic inflammatory myopathy: Elevated prevalence of esophageal involvement and differences according to autoantibody status and clinical subset.

INTRODUCTION: In this study we assessed high-resolution manometry (HRM) findings in patients with dermatomyositis and polymyositis. METHODS: From 2008 to 2015, we performed a cross-sectional study of myositis patients. A survey of esophageal symptoms and HRM data were analyzed and compared among different clinical and serologic groups. RESULTS: Twenty-four (45%) of the 53 patients included in the study had manometric involvement that was not correlated with any esophageal symptom (P = 0.8). Failed waves (34% vs. 0%, P = 0.004) and decreased upper esophageal sphincter pressure (50 vs. 70 mm Hg, P = 0.03) were more common in polymyositis than in dermatomyositis patients. Jackhammer esophagus was more common in anti-TIF1-γ patients (30% vs. 9%, P = 0.04), and lower esophageal sphincter involvement (47% vs. 25%, P = 0.03) was more prevalent in patients with the antisynthetase syndrome. CONCLUSIONS: Esophageal involvement is common in myositis patients, but it correlates poorly with esophageal symptoms. Specific clinical and serologic groups have different manometric features. Muscle Nerve 56: 386-392, 2017.

Possible implications of TGF-alpha in oesophageal dysmotility in systemic sclerosis.

OBJECTIVES: Hypoxia is a characteristic feature of systemic sclerosis (SSc).Transforming growth factor alpha (TGF-α) has an important role in excessive inflammation under hypoxic conditions. Since oesophageal dysmotility is one of the most common signs of SSc, the aim of this study was to explore the relation between TGF-α and oesophageal dysmotility in SSc. METHODS: The study included 35 patients with SSc and 32 healthy controls matched for sex and age. Serum concentrations of TGF-α were measured using ELISA. Oesophageal motility was assessed by oesophageal scintigraphy. A multiple-swallow test was performed in the study population with 99mTc-DTPA. A region of interest over the entire oesophagus was defined and the retention index (RI) was calculated. RESULTS: Statistically significant differences in serum concentration of TGF-α as well as of RI of 99mTc-DTPA were found between patients with SSc and healthy controls. A statistically significant correlation was found between serum concentrations of TGF-α and RIs of 99mTc-DTPA. This correlation was inverse, i.e. when serum concentrations of TGF-α increased, the RI of 99mTc-DTPA decreased (Spearman rho =-0361, p=0.033). CONCLUSIONS: These results point to a possible relation between TGF-α and oesophageal dysmotility in SSc. Although the results do not explain the exact role of this cytokine in the pathogenesis of esophageal changes, the finding of inverse correlation between TGF-α and oesophageal dysmotility is intriguing and requires further investigation.

Gastroparesis is associated with oxytocin deficiency, oesophageal dysmotility with hyperCCKemia, and autonomic neuropathy with hypergastrinemia.

BACKGROUND: Gastrointestinal (GI) dysmotility and autonomic neuropathy are common problems among diabetics with largely unknown aetiology. Many peptides are involved in the autonomic nervous system regulating the GI tract. The aim of this study was to examine if concentrations of oxytocin, cholecystokinin (CCK), gastrin and vasopressin in plasma differ between diabetics with normal function and dysfunction in GI motility. METHODS: Nineteen patients with symptoms from the GI tract who had been examined with gastric emptying scintigraphy, oesophageal manometry, and deep-breathing test were included. They further received a fat-rich meal, after which blood samples were collected and plasma frozen until analysed for hormonal concentrations. RESULTS: There was an increase in postprandial oxytocin plasma concentration in the group with normal gastric emptying (p = 0.015) whereas subjects with delayed gastric emptying had no increased oxytocin secretion (p = 0.114). Both CCK and gastrin levels increased after the meal, with no differences between subjects with normal respective delayed gastric emptying. The concentration of vasopressin did not increase after the meal. In patients with oesophageal dysmotility the basal level of CCK tended to be higher (p = 0.051) and those with autonomic neuropathy had a higher area under the curve (AUC) of gastrin compared to normal subjects (p = 0.007). CONCLUSION: Reduced postprandial secretion of oxytocin was found in patients with delayed gastric emptying, CCK secretion was increased in patients with oesophageal dysmotility, and gastrin secretion was increased in patients with autonomic neuropathy. The findings suggest that disturbed peptide secretion may be part of the pathophysiology of digestive complications in diabetics.

Esophageal and Gastric Dysmotilities are Associated with Altered Glucose Homeostasis and Plasma Levels of Incretins and Leptin.

BACKGROUND: Gastrointestinal complications in diabetes may affect glucose and endocrine homeostasis. Glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), and leptin regulate glucose homeostasis, food intake, and gastric emptying. AIM: The aim was to investigate associations between diabetes complications and glucose homeostasis and plasma levels of GIP, GLP-1, and leptin. METHODS: Sixteen diabetes patients (seven men) were examined with gastric emptying scintigraphy and 72-h continuous subcutaneous glucose monitoring, 14 with the deep-breathing test, and 12 with esophageal manometry. A fiber-rich breakfast was given during the second day of glucose registration. Blood samples were taken 10 min and right before a fat-rich breakfast, as well as 10, 20, 30, 45, 60, 90, 120, 150, and 180 min afterwards. 20 healthy volunteers acted as controls. Plasma was analyzed regarding GIP, GLP-1, and leptin by Luminex. RESULTS: Gastroparesis lowered maximal concentration (c-max) (p = 0.003) and total area under the curve (tAUC) (p = 0.019) of glucose levels as well as d-min (p = 0.043) of leptin levels. It tended to lower baseline (p = 0.073), c-max (p = 0.066), change from baseline (d-max) (p = 0.073), and tAUC (p = 0.093) of GLP-1 concentrations. Esophageal dysmotility tended to lower tAUC of glucose levels (p = 0.063), and c-min (p = 0.065) and tAUC (p = 0.063) of leptin levels. Diabetes patients had a higher baseline concentration of glucose (p = 0.013), GIP (p = 0.023), and leptin (p = 0.019) compared with healthy subjects. CONCLUSIONS: Gastric and esophageal dysmotility are associated with both lesser increases in postprandial glucose elevations and decreased postprandial changes in GLP-1 and leptin.

Plasma leptin concentrations and esophageal hypomotility in obese patients.

BACKGROUND: Although esophageal hypomotility is prevalent in obese patients, its cause remains unknown. Leptin, a hormone derived from adipose tissue, may be involved in this phenomenon because it has been shown to decrease gastric and intestinal motility in animals. It has been hypothesized that elevated plasma leptin concentration is a risk factor for esophageal dysmotility in obese patients. OBJECTIVE: To determine whether plasma leptin concentrations are higher in obese patients with esophageal hypomotility than in obese patients with a normal motility profile. METHOD: Fasting plasma leptin concentration (assessed by radioimmuoassay) was measured in all patients who were included in a study protocol investigating esophageal manometry before bariatric surgery. The patients completed standardized surveys regarding epidemiological data, upper gastrointestinal symptoms, medical history and medication(s). Basal levels of leptin, as well as corrected leptin scores adjusted for sex and body mass index, were compared in patients with and without esophageal dysmotility. RESULTS: Nine patients without dysmotility and eight with dysmotility were included. Both groups were comparable with regard to age (42±9 versus 38±9 years), sex (78% versus 75% women) and body mass index (49±10 kg/m2 versus 42±7 kg/m2). There were no significant differences regarding medication(s) and comorbidities between the two groups. When compared with normal predicted values, the corrected leptin scores were 30% higher in patients with dysmotility than in the control group with normal motility (P≤0.05). CONLCUSION: Obese patients with esophageal dysmotility exhibited elevated plasma leptin concentrations, suggesting a role for leptin in promoting esophageal hypomotility.

[Relationship among VIP plasma levels, esophageal dysfunction, and microcirculation in systemic sclerosis]. / Rapporti fra livelli plasmatici di VIP, disfunzione esofagea e del microcircolo in corso di sclerosi sistemica.

BACKGROUND: Recent studies suggest that esophageal dysmotility occurring in systemic sclerosis might be caused by neurotransmitter levels decrease. The aim of the present study is to value VIP plasma levels, and to relate them with the pressure of the inferior esophageal sphincter (IES) and the capillaroscopy score in a group of patients affected by Systemic Sclerosis (SSc). METHODS: Eleven subjects affected by SSc (eight male and three female, age from 30 to 72 years old) have been studied through esophageal manometry, capillaroscopy and VIP plasma levels evaluation. Fifteen healthy volunteers, as control group, have been enlisted. RESULTS: Our results show a decrease of VIP plasma levels in patients with SSc compared with control group. The difference between two groups has statistical significance (p < 0.01). Capillaroscopy has shown remarkable microcirculatory impairment and the esophageal manometry proved a decreased IES pressure. The scores of capillaroscopy, VIP plasma levels and pressures of IES have been compared and it has been observed that there is a relationship between VIP plasma level and pressure of IES. CONCLUSIONS: VIP plasma levels decrease enhances the role of the autonomic disorder in SSc and may contribute to produce the alteration of vascular tone as well as the gastroenteric musculature dysfunction.

High levels of leptin modulate esophageal motor characteristics in type 2 diabetic patients.

UNLABELLED: Leptin regulates gastric and intestinal motility, but its effect on oesophageal motility is unknown. We analyzed oesophageal manometric characteristics in diabetics with elevated leptin. METHODS: Fasting blood leptin levels were measured in 32 type 2 individuals aged from 39-81 years. An oesophageal stationary manometry was then performed. Each manometric door (P) registered one third of the oesophageal activity. Results are presented as mean +/- SD. RESULTS: Twenty-one subjects had elevated leptin (HLL) while 11 displayed normal levels (NLL). Peristaltic wave distributions (%) in NLL vs. HLL were 79.4 +/- 26.3 vs. 88.6 +/- 8.3 (p = 0.2). Simultaneous and retrograde waves showed similar trends. Non-transmitted waves were 16.1 +/- 26.5 vs. 4.6 +/- 4.5% (p < 0.05). Amplitudes in NLL vs. HLL (in mm Hg) were P1: 30.2 +/- 10.8 vs. 33.2 +/- 11.7 (p = 0.4), P2: 38.4 +/- 14.4 vs. 58.0 +/- 21.2 (p = 0.01), P3: 42.4 +/- 14.4 vs. 64.7 +/-2 8.3 (p < 0.006), and average amplitudes: 37.1 +/- 12.1 vs. 52.1 +/- 17.6 (p = 0.01). Wave average upstroke (in mm Hgs) was P1: 25.6 +/- 19.1 vs. 23.3 +/- 10.1 (p = 0.6), P2: 26.8 +/- 10.7 vs. 36.2 +/- 11.6 (p < 0.03), and P3: 25.5 +/- 9.1 vs. 34.1 +/- 16.3, (p < 0.06). Wave maximum upstroke was P1: 39.0 +/- 18.6 vs. 40.5 +/- 13.8, (p = 0.8), P2: 45.5 +/- 15.5 vs. 63.8 +/- 19.2 (p = 0.01), P3: 46.6 +/- 17.8 vs. 65.0 +/- 29.1 (p <0.03). Wave duration in distal oesophagus was 4.5 +/- 0.7 vs. 5.5 +/- 1.1 s (p = 0.01), and velocity 3.3 +/- 3.3 vs. 2.96 +/- 3.7 cm/s (p = 0.6). CONCLUSION: 1--Non-transmitted waves were slightly higher in NLL. 2--In medium and distal oesophagus, the wave amplitude, medium and maximum upstroke, and duration in distal oesophagus were increased in HLL.

Patients with irritable bowel syndrome and dysmotility express antibodies against gonadotropin-releasing hormone in serum.

BACKGROUND: The etiology of irritable bowel syndrome (IBS) and dysmotility is in most cases unknown. Organic, pathognomonic changes have not been described. We have previously demonstrated sporadic expressions of antibodies against gonadotropin-releasing hormone (GnRH) in serum from these patients. The aim of this study was to screen for the presence of GnRH antibodies in healthy subjects and patients with gastrointestinal (GI) diseases. METHODS: Consecutive patients suffering from either IBS, idiopathic dysmotility, GI complaints secondary to diabetes mellitus, celiac disease or inflammatory bowel disease (IBD) were included. Healthy blood donors served as controls. Blood samples were taken for analyzing IgM and IgG antibodies against GnRH using an ELISA method. Medical records were scrutinized with respect to duration of symptoms, co-existing diseases, drug treatments, hereditary factors, and laboratory analyses. KEY RESULTS: Healthy controls expressed low levels of GnRH IgM antibodies in a prevalence of 23%. The prevalence of GnRH IgM antibodies in IBS and dysmotility patients was 42% (P = 0.008), and the levels were higher (P = 0.000). Patients with diabetes mellitus expressed GnRH IgM antibodies in the same prevalence as controls (25%), but in higher levels (P = 0.02). Patients with celiac disease or IBD had the same or lower levels of antibodies. There were no associations between antibodies, other co-existing diseases or laboratory analyses. CONCLUSIONS & INFERENCES: Higher levels of GnRH IgM antibodies were detected in patients with IBS and dysmotility, but not organic GI diseases, compared with healthy controls. These findings suggest that IBS and dysmotility to some extent may be of an autoimmune origin.

Motilin concentrations in relation to gastro intestinal dysmotility in diabetes mellitus.

AIM: Dysmotility in the upper gastro intestinal (GI) tract are common problems in diabetics. Many peptides are involved in the regulation of the motility. The aim of this study was to examine whether plasma levels of motilin were related to dysfunction in the oesophagus and stomach in a well-defined diabetic patient group. METHODS: Nineteen patients with symptoms from the GI tract who had been examined with oesophageal manometry, gastric emptying scintigraphy and deep-breathing test were included. They received a fat-rich meal, after which blood samples were collected and analysed for motilin concentrations. RESULTS: Symptoms of abdominal fullness and gastro oesophageal reflux significantly associated with delayed gastric emptying, whereas no symptom correlated to oesophageal dysmotility. Plasma levels of motilin were increased after the fat-rich meal (p=0.000), with no difference between the groups. Abnormal manometry was characterized by aperistalsis and/or simultaneous contractions. The percentage of simultaneous contractions correlated to basic and peak motilin values (r(s)=0.898, p=0.006 and r(s)=0.842, p=0.017, respectively). Gastric emptying did not influence motilin concentrations. CONCLUSION: Plasma motilin concentrations vary with abnormalities of oesophageal motility in diabetics, but not with abnormalities of gastric emptying.

Oesophageal dysmotility, delayed gastric emptying and autonomic neuropathy correlate to disturbed glucose homeostasis.

AIMS/HYPOTHESIS: Among diabetic patients, glucose homeostasis may be affected by abnormal gastrointestinal motility and autonomic neuropathy. This study analysed whether oesophageal dysmotility, delayed gastric emptying or autonomic neuropathy affect glucose homeostasis. MATERIALS AND METHODS: Oesophageal manometry and gastric emptying scintigraphy were performed in 20 diabetic patients. Heart-rate variation during deep breathing (expiration/inspiration [E/I] ratio) and continuous subcutaneous glucose concentrations for a period of 72 h were also monitored in the same patients. RESULTS: Oesophageal dysmotility was found in eight of 14 patients. Eleven of 20 patients had delayed gastric emptying (abnormal gastric emptying half-time [T (50)]) and nine of 18 had an abnormal E/I ratio. Complaints of abdominal fullness were predictive of delayed gastric emptying. A low peristaltic speed of the oesophagus was associated with impaired T (50) (r ( s )=-0.67; p=0.02). One hour after breakfast, subcutaneous glucose levels decreased in patients with delayed gastric emptying but continued to rise in those with normal emptying. Consequently, the median glucose level 2.5 h after breakfast was lower in the former (9.1 [4.2-12.5] vs 14.3 [11.2-17.7] mmol/l; p<0.05). Glucose fluctuations during the 72 h were significantly higher in patients with an abnormal E/I ratio than in those with a normal E/I ratio (coefficient of variation: 41 [46-49] vs 28 [27-34]%; p=0.008). CONCLUSIONS/INTERPRETATION: Abdominal fullness predicted delayed gastric emptying that was associated with diminished glucose uptake after breakfast. Low oesophageal peristaltic speed was associated with slow gastric emptying whereas parasympathetic neuropathy was associated with increased glucose variations.