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  • Sayin, Sama I., et al. (författare)
  • Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist.
  • 2013
  • Ingår i: Cell metabolism. - 1932-7420. ; 17:2, s. 225-35
  • Tidskriftsartikel (refereegranskat)abstract
    • Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. Bile acid synthesis is under negative feedback control through activation of the nuclear receptor farnesoid X receptor (FXR) in the ileum and liver. Here we profiled the bile acid composition throughout the enterohepatic system in germ-free (GF) and conventionally raised (CONV-R) mice. We confirmed a dramatic reduction in muricholic acid, but not cholic acid, levels in CONV-R mice. Rederivation of Fxr-deficient mice as GF demonstrated that the gut microbiota regulated expression of fibroblast growth factor 15 in the ileum and cholesterol 7α-hydroxylase (CYP7A1) in the liver by FXR-dependent mechanisms. Importantly, we identified tauro-conjugated beta- and alpha-muricholic acids as FXR antagonists. These studies suggest that the gut microbiota not only regulates secondary bile acid metabolism but also inhibits bile acid synthesis in the liver by alleviating FXR inhibition in the ileum.
  • Choung, Rok Seon, et al. (författare)
  • Community-Based Study of Celiac Disease Autoimmunity Progression in Adults
  • 2020
  • Ingår i: Gastroenterology. - 1528-0012 .- 0016-5085. ; 158:1, s. 151-159
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Celiac disease can develop at any age, but outcomes of adults with positive results from serologic tests for tissue transglutaminase antibodies (tTGA) without endoscopic determination of celiac disease (called celiac autoimmunity) have not been thoroughly evaluated. We investigated the proportion of adults with celiac autoimmunity at a community medical center and their progression to celiac disease. Methods: We analyzed waste blood samples from a community clinic from 15,551 adults for tTGA and, if titer results were above 2 U/mL, for endomysial antibody. The blood samples had been collected at 2 time points (median interval, 8.8 years) from 2006 through 2017. We collected data from the clinic on diagnoses of celiac disease based on duodenal biopsy analysis. Results: Of the serum samples collected at the first time point, 15,398 had negative results for tTGA, and 153 had positive results for tTGA (>4 U/mL). Based on medical records, 6 individuals received a diagnosis of celiac disease, for a cumulative incidence of celiac disease diagnosis of 0.06% (95% confidence interval, 0.01–0.11). Forty-nine (0.32%) individuals with a negative result from the first serologic test for tTGA had a positive result from the second test. Among the 153 adults who were tTGA positive at the first time point, 31 (20%) had a subsequent diagnosis of celiac disease, 81 (53%) remained positive for tTGA without a clinical diagnosis of celiac disease, and 41 (27%) had negative test results for tTGA at the second time point. Higher initial tTGA titers, female sex, and a history of hypothyroidism and autoimmune disease were associated with increased risks of subsequent diagnosis of celiac disease. Interestingly, adults whose first blood sample had a positive test result but second blood sample had a negative result for tTGA were older, had lower-than-average initial tTGA titer results, and had a higher mean body mass index than adults whose blood samples were positive for tTGA at both time points and adults later diagnosed with celiac disease. Conclusions: In an analysis of serum samples collected from a community clinic an average of 8.8 years apart, we found that fewer than 1% of adults with negative results from an initial test for tTGA have a positive result on a second test. Of adults with positive results from the test for tTGA, only 20% are later diagnosed with celiac disease; the remaining individuals maintain persistent increases in tTGA without diagnoses of celiac disease or have negative results from second tests.
  • Polster, Annikka, et al. (författare)
  • Heart rate variability characteristics of patients with irritable bowel syndrome and associations with symptoms
  • 2018
  • Ingår i: Neurogastroenterology and Motility. - 1350-1925. ; 30:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Disturbed brain-gut interactions are assumed to be of importance for symptom generation in patients with irritable bowel syndrome (IBS). The autonomic nervous system (ANS) is part of the bidirectional brain-gut communication, but previous studies in IBS show diverging results. We aimed to identify subgroups of IBS patients with distinct ANS characteristics differentiating them from healthy controls (HC), and to study associations between ANS status and symptoms. Methods: Heart rate variability (HRV) was measured in IBS patients and HC (Holter monitoring: supine and standing positions with controlled respiration and ambulatory 24-hour period). Frequency (5 minutes, supine, standing) and time domains (24 hours, day, night) were analyzed. Validated questionnaires were used to measure gastrointestinal and psychological symptoms in patients. Patients and HC were compared on a univariate and multivariate level (principal component analysis [PCA] and orthogonal partial least squares discriminatory analysis (OPLS-DA)). Key Results: We analyzed 158 IBS patients (Rome III) and 39 HC. Patients differed significantly from HC in HRV parameters during daytime and in standing position. In the PCA, a majority of patients overlapped with HC, but the weighted means differed (P <.01). A subset of patients (n = 30; 19%) with an aberrant global HRV profile was identified through PCA and OPLS-DA; these patients reported more severe symptoms of frequent (P <.05) and loose stools (P =.03), as well as urgency (P =.01). Conclusions and Inferences: Altered ANS function was demonstrated in patients with IBS, and this might be of particular relevance for symptoms in a subset of the patients.
  • Laurell, Helena, et al. (författare)
  • Acute abdominal pain among elderly patients
  • 2006
  • Ingår i: Gerontology. - 0304-324X .- 1423-0003. ; 52:6, s. 339-344
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Diagnosis of acute abdominal pain in older persons is a challenge, with the age-related increase in concurrent diseases. In most western countries the number of elderly people is constantly rising, which means that an increasing proportion of patients admitted for abdominal pain at the emergency department are elderly. Objective: To characterize differences in clinical presentation and diagnostic accuracy between younger and more elderly patients with acute abdominal pain. Methods: Patients admitted to Mora Hospital with abdominal pain of up to seven days' duration were registered according to a detailed schedule. From 1st February 1997 to 1st June 2000, 557 patients aged 65-79 years and 274 patients aged ≥80 years were registered. Patients aged 20-64 years (n = 1,458) served as a control group. Results: A specific diagnosis, i.e. other than 'non-specific abdominal pain', was established in 76 and 78% of the patients aged 65-79 and ≥80 years respectively, and in 64% of those aged 20-64 (p < 0.001). Pain duration before admission increased with age (p < 0.003), as did frequency and duration of hospitalization (p < 0.0001). Hospital stay increased from 170 days per 100 emergency admissions in the control group to 320 and 458 days in the younger and older study groups, respectively. At the emergency department, older patients were more often misdiagnosed than control patients (52 vs. 45%; p = 0.002). At discharge the diagnosis was more accurate in the control group (86 vs. 77%; p < 0.0001). Hospital mortality was higher among older patients (23/831 vs. 2/1,458; p < 0.001). The admission-to-surgery interval was increased (1.8 vs. 0.9 days, p < 0.0001) in patients ≥65 years. Rebound tenderness (p < 0.0001), local rigidity (p = 0.003) and rectal tenderness (p = 0.004) were less common in the older than in the control patients with peritonitis. In patients ≥65 years, C-reactive protein did not differ between patients operated on and those not, contrary to the finding in patients <65 years (p<0.0001). Conclusion: Both the preliminary diagnosis at the emergency department and the discharge diagnosis were less reliable in elderly than in younger patients. Elderly patients more often had specific organic disease and arrived at the emergency department after a longer history of abdominal pain compared to younger patients.
  • Abdelrahman, Islam, 1982-, et al. (författare)
  • Evaluation of Glandular Liposculpture as a Single Treatment for Grades I and II Gynaecomastia
  • 2018
  • Ingår i: Aesthetic Plastic Surgery. - Springer. - 0364-216X. ; 42:2, s. 1222-1230
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundGynaecomastia is a benign enlargement of the male breast, of which the psychological burden on the patient can be considerable, with the increased risk of disorders such as depression, anxiety, and social phobia. Minimal scarring can be achieved by liposuction alone, though it is known to have a limited effect on the dense glandular and fibroconnective tissues. We know of few studies published on “liposuction alone”, so we designed this study to evaluate the outcome of combining liposuction with glandular liposculpturing through two axillary incisions as a single treatment for the management of grades I and II gynaecomastia.MethodsWe made a retrospective analysis of 18 patients with grade I or II gynaecomastia who were operated on by combined liposuction and glandular liposculpturing using a fat disruptor cannula, without glandular excision, during the period 2014–2016. Patient satisfaction was assessed using the Breast Evaluation Questionnaire (BEQ), which is a 5-point Likert scale (1 = very dissatisfied; 2 = dissatisfied; 3 = neither; 4 = satisfied; 5 = very satisfied). The post-operative aesthetic appearance of the chest was evaluated by five independent observers on a scale from 1 to 5 (5 = considerable improvement).ResultsThe patient mean (SD) overall satisfaction score was 4.7 (0.7), in which 92% of the responders were “satisfied” to “very satisfied”. The mean (SD) BEQ for all questions answered increased from 2.1 (0.2) “dissatisfied” preoperatively to 4.1 (0.2) “satisfied” post-operatively. The observers’ mean (SD) rate for the improvement in the shape of the front chest wall was 4.1 (0.7). No haematomas were recorded, one patient developed a wound infection, and two patients complained of remnants of tissue. The median (IQR) body mass index was 27.4 (26.7–29.4), 11 patients had gynaecomastia grade I, and 7 patients grade II. The median (IQR) volume of aspirated fat was 700 ml (650–800), operating time was 67 (65–75) minutes, 14 patients had general anaesthesia, and hospital charges were US$ 538 (481–594).ConclusionsCombined liposuction and liposculpturing using the fat disruptor cannula resulted in satisfied patients and acceptable outcomes according to the observers’ ratings. It could be a useful alternative with an outcome that corresponds to that of more expensive methods.
  • Ahlman, Håkan, 1947-, et al. (författare)
  • Somatostatin receptors on neuroendocrine tumors--a way to intraoperative diagnosis and localization.
  • 1994
  • Ingår i: The Yale journal of biology and medicine. - 0044-0086. ; 67:3-4, s. 215-21
  • Tidskriftsartikel (refereegranskat)abstract
    • Intraoperative radionuclide detection using 111In-DTPA-D-Phe1-octreotide was evaluated in five patients with midgut carcinoids and in three patients with recurrent medullary thyroid carcinoma. Three different time intervals (24, 48 and 120 hr) from injection of the radiopharmaceutical to surgery were used. At surgery, suspect tumors were measured by probe in situ and ex vivo after excision. All tissue specimens and blood samples withdrawn during surgery were measured for 111In activity, and tissue/blood activity concentration ratios were calculated. In situ measurements were valuable especially in neck surgery, where the probe was helpful not only in localization of tumors but also in the control of tumor clearance. Ex vivo measurements were helpful in diagnosing tumor tissue. All five patients with midgut carcinoids were somatostatin receptor-positive, while only three out of seven patients with medullary thyroid carcinoma were receptor-positive. The tissue/blood activity concentration ratios and probe measurement ratios were in general higher in patients with midgut carcinoid than in patients with medullary thyroid carcinoma. Of particular interest were the high tissue/blood concentration ratios in all receptor-positive patients at all time intervals studied. This fact suggests a potential role for radiolabelled octreotide in radiotherapy of these tumor types.
  • Aleman, Soo, et al. (författare)
  • A Risk for Hepatocellular Carcinoma Persists Long-term After Sustained Virologic Response in Patients With Hepatitis C-Associated Liver Cirrhosis
  • 2013
  • Ingår i: Clinical Infectious Diseases. - The Infectious Diseases Society of America. - 1537-6591. ; 57:2, s. 230-236
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. The long-term effect of sustained virologic response (SVR) to antiviral therapy on the risk of developing hepatocellular carcinoma (HCC), liver complications, liver-related death, and overall death in hepatitis C virus (HCV)-infected patients with liver cirrhosis is not fully known. Methods. These risks were evaluated during long-term follow-up in 351 patients with HCV-related cirrhosis. One hundred ten patients with SVR, 193 with non-SVR, and 48 who were untreated were included in a multicenter cohort that was initiated in 2001 and prospectively followed up for a mean of 5.3 (SD, 2.8) years. Complementary follow-up data from national registries were used to minimize the loss of patients during follow-up. Results. Six patients with SVR developed HCC at 0.04, 0.64, 2.4, 7.4, 7.4, and 7.6 years, respectively, after achieving SVR. The incidences of HCC, any liver complication, liver-related death, and overall death per 100 person-years were significantly lower in SVR time with 1.0, 0.9, 0.7, and 1.9, compared to 2.3, 3.2, 3.0, and 4.1 in non-SVR and 4.0, 4.9, 4.5, and 5.1 in untreated time. The long-term consequences did not decline significantly after >3 years versus during the first 3 years of follow-up. Conclusions. The risk for HCC, liver decompensation, and death in patients with liver cirrhosis related to HCV was markedly reduced after SVR, but a long-term risk of developing HCC remains for up to 8 years. Cirrhotic patients with HCV who achieve SVR should therefore maintain long-term surveillance for HCC. Future studies aimed to better identify those with remaining long-term risk for HCC are needed.
  • Andersson, P, et al. (författare)
  • Internalization of indium-111 into human neuroendocrine tumor cells after incubation with indium-111-DTPA-D-Phe1-octreotide.
  • 1996
  • Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 37:12, s. 2002-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuroendocrine tumor cells frequently overexpress somatostatin receptors at their cell surfaces. To evaluate the possibility of using the somatostatin analog 111In-DTPA-D-Phe1-octreotide for radiation therapy, we studied the binding and subsequent internalization of 111In into three types of cultured human neuroendocrine tumor cells.
  • Arora, Tulika, et al. (författare)
  • Diabetes-associated microbiota in fa/fa rats is modified by Roux-en-Y gastric bypass
  • 2017
  • Ingår i: Isme Journal. - 1751-7362. ; 11:9, s. 2035-2046
  • Tidskriftsartikel (refereegranskat)abstract
    • Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with shamoperated fa/fa rats in all intestinal segments, and their microbiota composition resembled that of unoperated fa/+ rats. To investigate the functional role of RYGB-associated microbiota alterations, we transferred microbiota from sham-and RYGB-treated fa/fa rats to germ-free mice. The metabolic phenotype of RYGB-treated rats was not transferred by the transplant of ileal microbiota. In contrast, postprandial peak glucose levels were lower in mice that received cecal microbiota from RYGBversus sham-operated rats. Thus, diabetes-associated microbiota alterations in fa/fa rats can be modified by RYGB, and modifications in the cecal microbiota may partially contribute to improved glucose tolerance after RYGB.
  • Backman, Olof, et al. (författare)
  • Gastric Bypass Surgery Reduces De Novo Cases of Type 2 Diabetes to Population Levels : A Nationwide Cohort Study From Sweden
  • 2019
  • Ingår i: Annals of Surgery. - Lippincott Williams & Wilkins. - 0003-4932. ; 269:5, s. 895-902
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The aim of this study was to determine long-term changes in pharmacological treatment of type 2 diabetes after primary Roux-en-Y gastric bypass (RYGB) surgery, in patients with and without pharmacological treatment of diabetes preoperatively.SUMMARY OF BACKGROUND DATA: Several studies have shown that gastric bypass has good effect on diabetes, at least in the short-term. This study is a nationwide cohort study using Swedish registers, with basically no patients lost to follow-up during up to 7 years after surgery.METHODS: The effect of RYGB on type 2 diabetes drug treatment was evaluated in this nationwide matched cohort study. Participants were 22,047 adults with BMI ≥30 identified in the nationwide Scandinavian Surgical Obesity Registry, who underwent primary RYGB between 2007 and 2012. For each individual, up to 10 general population comparators were matched on birth year, sex, and place of residence. Prescription data were retrieved from the nationwide Swedish Prescribed Drug Register through September 2015. Incident use of pharmacological treatment was analyzed using Cox regression.RESULTS: Sixty-seven percent of patients with pharmacological treatment of type 2 diabetes before surgery were not using diabetes drugs 2 years after surgery and 61% of patients were not pharmacologically treated up to 7 years after surgery. In patients not using diabetes drugs at baseline, there were 189 new cases of pharmacological treatment of type 2 diabetes in the surgery group and 2319 in the matched general population comparators during a median follow-up of 4.6 years (incidence: 21.4 vs 27.9 per 10,000 person-years; adjusted hazard ratio 0.77, 95% confidence interval 0.67-0.89; P < 0.001).CONCLUSIONS: Gastric bypass surgery not only induces remission of pharmacological treatment of type 2 diabetes but also protects from new onset of pharmacological diabetes treatment. The effect seems to persist in most, but not all, patients over 7 years of follow-up.
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