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- Halim, Md Abdul, et al.
(författare)
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GLP-1 acts at myenteric neurons to inhibit motility in humans: results of in vivo motility studies and in vitro characterization of responses to GLP-1 and ROSE-010 : GLP-1 and digestive motility
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Glucagon-like peptide-1 (GLP-1) is secreted from L-cells after nutrient ingestion, inhibiting motility. Aims: To clarify whether infused GLP-1 inhibits in vivo prandial motility response and determine the likeliest target cell type and mechanism of action of GLP-1 and its analogue ROSE-010 using in vitro human gut muscle strips. Methods: Sixteen healthy volunteers underwent antroduodenojejunal manometry. Recordings of 1 hour infusion of saline or GLP-1 (0.7 or 1.2 pmol/kg/min) were compared. Plasma GLP-1 and GLP-2 were measured by RIA. Gastrointestinal muscle strips from surgical re-sections, pre-contracted with bethanechol or electric field stimulation (EFS), were investigated for GLP-1 or ROSE-010 induced relaxation. Receptors for GLP-1 and GLP-2 (GLP-1R, GLP-2R) were visualized by immunohistochemistry. Mechanisms were studied employing exendin(9-39) amide, Lw-nitro-monomethyl arginine (L-NMMA), 2´5´-dideoxyadenosine (DDA) and tetrodotoxin (TTX). Results: Food-intake increased motility index from 4.0±0.5 to 6.4±0.3 (antrum), 4.2±0.4 to 5.7±0.4 (duodenum) and 4.6±0.3 to 5.9±0.2 (jejunum) ln(Σ(mmHg·s·min-1)). GLP-1 at 0.7 pmol/kg/minwas sufficient to suppress these indexes from 6.2±0.4 to 3.8±0.7, 5.6±0.6 to 3.9±0.6 and 5.8±0.1 to 4.6±0.4 ln(Σ(mmHg·s·min-1)). Both GLP-1 doses raised plasma GLP-1, but not GLP-2. GLP-1 (EC50 40 nM) and ROSE-010 (EC50 50 nM) relaxed bethanechol-induced contractions in muscle strips. Inhibitory responses were blocked by exendin(9-39) amide, L-NMMA, DDA or TTX pre-treatment. GLP-1R and GLP-2R were expressed in myenteric neurons, but not muscle. Conclusions: GLP-1 and ROSE-010 inhibit motility through GLP-1R at myenteric neurons, which also possess GLP-2 receptors. GLP-1 increases more than GLP-2 with meals and does not increase plasma GLP-2. GLP-1 and ROSE-010 relaxations are cAMP and NO dependent.
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- Hultman, Bo, 1964-, et al.
(författare)
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A population-based study of incidence of peritoneal metastases and prognostic factors in patients with loco-regionally advanced gastric cancer
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Purpose The aim was to investigate epidemiological and prognostic factors as a knowledge base for the treatment of patients with loco-regionally advanced gastric cancer (GC). Methods In Uppsala County between 2000 and 2009, two hundred and fifty-five patients with GC were identified. Data from patient records were analyzed for loco-regionally advanced GC, defined as tumor invading the parietal and/or visceral peritoneum, including peritoneal metastasis but excluding serosal invasion from the primary tumor only, at primary diagnosis or during follow-up. Presence or absence of distant metastasis (DM) in these patients was also assessed. Results One hundred and twenty patients (47% of all patients with GC) experienced loco-regionally advanced disease. Forty-one percent also had DM. Median overall survival (mOS) from diagnosis of local-regionally advanced disease was 4.8 months for the whole group of patients, 5.1 months for the subgroup of patients without DM and 4.7 months for the subgroup with DM. Using multivariate Cox analysis, positive prognostic factors for survival identified were good performance status and treatment with palliative chemotherapy and/or radiotherapy. Synchronous DM was a negative predictive factor. The mOS did not differ between the first and second time period. Discussion Peritoneal metastasis from GC is more common than previously reported. The lack of improvement in OS over the past decade signals a need for new treatment strategies.
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- Jestin Hannan, Christine, et al.
(författare)
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Atelectasis formation and pleural effusion after esophagectomy : postoperative radiologic comparison of thoracoscopic versus open surgery
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Esophagectomy entails risk for postoperative pulmonary complications. In clinical practice, these might be reduced by minimal invasive esophagectomy (MIE). We tested the hypothesis that pulmonary findings on postoperative computed tomography (CT) differed between open esophagectomy and MIE. Secondarily, we present a suggestion for standardized CT-evaluation in these patients.Method: Postoperative (day 5) CT thorax from 40 patients (20 open and 20 MIE) who had undergone esophagectomy were reviewed. On an axial view, the areas of atelectasis and pleural effusion were measured at one and five centimetres above the right diaphragmatic dome and at the level of the carina. Additionally, the total distribution of atelectasis and pleural effusion was estimated on an ordinal scale (0-5), with ≥ 3 considered clinically important.Results: The groups were well-matched in terms of age, sex, and smoking status. There were no statistically significant differences in the areas of atelectasis or pleural effusion for open surgery compared with MIE. Neither did the groups differ in the proportion of patients subjective of clinically important atelectasis (dx: 30% vs. 25%, sin: 65% vs. 65%) or pleural effusion (dx: 15% vs. 15%, sin: 65% vs. 45%). More pleural effusion and atelectasis at the 1 cm level was present on the left side.Conclusion: Despite major differences in surgical access, there were no differences in postoperative atelectasis or pleural effusion between the two procedures. Less right-sided pleural effusion demonstrates the effect of surgical drains. The present measurements, performed at clear anatomical landmarks, can be of value in future studies.
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- Löfling Skogar, Martin, 1983-, et al.
(författare)
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Complications, Adverse Events and Healthcare Consumption the First Ten Years after Duodenal Switch and Gastric Bypass in a Matched National Cohort
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background:Roux-en-Y Gastric Bypass (RYGB), risk unsatisfactory weight loss in super obese patients. Duodenal switch (DS) is more effective, however, considered to have an increased complication rate. Objectives:To compare early complications, healthcare consumption, long-term adverse events and mortality up until 10 years after primary DS and RYGB, respectively. Setting:Nationwide study in Sweden Methods:In this nationwide population-based cohort study, propensity-score matching (1DS:4RYGB) was used. Five national registers were cross-matched; the Scandinavian Obesity Surgery Register (perioperative data), the Prescribed Drug Register (comorbidities, i.e. medication for the specific conditions), Statistics Sweden (socioeconomic data), the National Patient Register (subsequent healthcare) and the Death Register (mortality). Results:The study population consisted of 333 DS and 1332 RYGB, operated 2007-2017 (BMI of 55 kg/m2, 38.5 years and 60.7% females). Early complications (≤30 days) were more common after DS (15.3% vs. 8.1%, p<0.01). Hospital admissions and in-hospital days over the 10-year period were similar (1.3 vs. 1.1 admission, p=0.30 and 6.6 vs. 7.2 in-hospital days, p=0.81), while DS had more visits to specialized outpatient clinics (7.1 vs. 4.2, p<0.01). DS were associated with an increased risk of protein-malnutrition/malabsorption (OR 11.7 [3.1-43.5]) and having an additional abdominal operation (any type) (OR 1.9 [1.4-2.6]). Overall mortality did not differ between groups. Conclusion:DS was associated with more early complications and an increased risk for protein-malnutrition/malabsorption and more additional abdominal surgeries, however, the overall mortality and long-term requirement of in-hospital care were similar to RYGB.
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- Löfling Skogar, Martin, 1983-, et al.
(författare)
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Weight loss, Effect on Comorbidities and Quality of Life in the Long Term after Duodenal Switch and Gastric Bypass : A population-based cohort study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective:To compare long-term weight-loss, effect on comorbidities and quality of life after duodenal switch (DS) and gastric bypass (RYGB) in super obese patients. Background:Unsatisfactory weight loss is common after bariatric surgery in patients with super obesity (Body Mass Index [BMI]≥50 kg/m2). Unfortunately, this group of patients is increasing worldwide. Methods:Population-based cohort-study of primary DS and RYGB (BMI≥48 kg/m2), in Sweden 2007-2017, with cross-matching of four national registers. Baseline characteristics were used for propensity score matching (1DS:4RYGB). Weight loss and quality of life were analyzed up until 5 years after surgery. Medication for obesity-related conditions (diabetes, hypertension, dyslipidemia, depression, pain) and gastrointestinal symptoms were analyzed up until 10 years. Results:The study population consisted of 333 DS and 1332 RYGB, with 60.7% females, 38.5 years old and BMI 55.0 kg/m2at baseline. DS resulted in a lower BMI at 5 years compared to RYGB, 32.2±5.5 and 37.8±7.3, respectively, (p<0.01). DS reduced prevalence of diabetes and hypertension more than RYGB, while reduction in dyslipidemia was similar for both groups, during the 10-year follow-up. Both groups increased their use of anti-depressants and a maintained a high use of opioids. Reflux and diarrhea were more common after DS. Improvement in physical quality of life was seen for both groups, with superior improvement after DS. Mental quality of life remained unchanged at 5 years. Conclusion:This study indicates that super obese patients have a more favorable outcome after DS compared to RYGB, regarding weight loss, effect on diabetes and hypertension, and physical quality of life.
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