| 1. |
- Alfirevic, Andrej, et al.
(author)
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Serratus anterior and pectoralis plane blocks for robotically assisted mitral valve repair : a randomised clinical trial
- 2023
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In: British Journal of Anaesthesia. - 0007-0912. ; 130:6, s. 786-794
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Journal article (peer-reviewed)abstract
- Background: Minimally invasive cardiac surgery provokes substantial pain and therefore analgesic consumption. The effect of fascial plane blocks on analgesic efficacy and overall patient satisfaction remains unclear. We therefore tested the primary hypothesis that fascial plane blocks improve overall benefit analgesia score (OBAS) during the initial 3 days after robotically assisted mitral valve repair. Secondarily, we tested the hypotheses that blocks reduce opioid consumption and improve respiratory mechanics. Methods: Adults scheduled for robotically assisted mitral valve repairs were randomised to combined pectoralis II and serratus anterior plane blocks or to routine analgesia. The blocks were ultrasound-guided and used a mixture of plain and liposomal bupivacaine. OBAS was measured daily on postoperative Days 1–3 and were analysed with linear mixed effects modelling. Opioid consumption was assessed with a simple linear regression model and respiratory mechanics with a linear mixed model. Results: As planned, we enrolled 194 patients, with 98 assigned to blocks and 96 to routine analgesic management. There was neither time-by-treatment interaction (P=0.67) nor treatment effect on total OBAS over postoperative Days 1–3 with a median difference of 0.08 (95% confidence interval [CI]: –0.50 to 0.67; P=0.69) and an estimated ratio of geometric means of 0.98 (95% CI: 0.85–1.13; P=0.75). There was no evidence of a treatment effect on cumulative opioid consumption or respiratory mechanics. Average pain scores on each postoperative day were similarly low in both groups. Conclusions: Serratus anterior and pectoralis plane blocks did not improve postoperative analgesia, cumulative opioid consumption, or respiratory mechanics during the initial 3 days after robotically assisted mitral valve repair. Clinical trial registration: NCT03743194.
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| 2. |
- Asplund, Olof, et al.
(author)
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Islet Gene View-a tool to facilitate islet research
- 2022
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In: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 5:12
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Journal article (peer-reviewed)abstract
- Characterization of gene expression in pancreatic islets and its alteration in type 2 diabetes (T2D) are vital in understanding islet function and T2D pathogenesis. We leveraged RNA sequencing and genome-wide genotyping in islets from 188 donors to create the Islet Gene View (IGW) platform to make this information easily accessible to the scientific community. Expression data were related to islet phenotypes, diabetes status, other islet-expressed genes, islet hormone-encoding genes and for expression in insulin target tissues. The IGW web application produces output graphs for a particular gene of interest. In IGW, 284 differentially expressed genes (DEGs) were identified in T2D donor islets compared with controls. Forty percent of DEGs showed cell-type enrichment and a large proportion significantly co-expressed with islet hormone-encoding genes; glucagon (GCG, 56%), amylin (IAPP, 52%), insulin (INS, 44%), and somatostatin (SST, 24%). Inhibition of two DEGs, UNC5D and SERPINE2, impaired glucose-stimulated insulin secretion and impacted cell survival in a human beta-cell model. The exploratory use of IGW could help designing more comprehensive functional follow-up studies and serve to identify therapeutic targets in T2D.
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| 3. |
- Egerod, Kristoffer L, et al.
(author)
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A Major Lineage of Enteroendocrine Cells Coexpress CCK, Secretin, GIP, GLP-1, PYY, and Neurotensin but Not Somatostatin.
- 2012
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In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170.
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Journal article (peer-reviewed)abstract
- Enteroendocrine cells such as duodenal cholecystokinin (CCK cells) are generally thought to be confined to certain segments of the gastrointestinal (GI) tract and to store and release peptides derived from only a single peptide precursor. In the current study, however, transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of the CCK promoter demonstrated a distribution pattern of CCK-eGFP positive cells that extended throughout the intestine. Quantitative PCR and liquid chromatography-mass spectrometry proteomic analyses of isolated, FACS-purified CCK-eGFP-positive cells demonstrated expression of not only CCK but also glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide (GIP), peptide YY (PYY), neurotensin, and secretin, but not somatostatin. Immunohistochemistry confirmed this expression pattern. The broad coexpression phenomenon was observed both in crypts and villi as demonstrated by immunohistochemistry and FACS analysis of separated cell populations. Single-cell quantitative PCR indicated that approximately half of the duodenal CCK-eGFP cells express one peptide precursor in addition to CCK, whereas an additional smaller fraction expresses two peptide precursors in addition to CCK. The coexpression pattern was further confirmed through a cell ablation study based on expression of the human diphtheria toxin receptor under the control of the proglucagon promoter, in which activation of the receptor resulted in a marked reduction not only in GLP-1 cells, but also PYY, neurotensin, GIP, CCK, and secretin cells, whereas somatostatin cells were spared. Key elements of the coexpression pattern were confirmed by immunohistochemical double staining in human small intestine. It is concluded that a lineage of mature enteroendocrine cells have the ability to coexpress members of a group of functionally related peptides: CCK, secretin, GIP, GLP-1, PYY, and neurotensin, suggesting a potential therapeutic target for the treatment and prevention of diabetes and obesity.
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| 4. |
- Falkmer, Ursula G., et al.
(author)
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Malignant presacral ghrelinoma with long-standing hyperghrelinaemia
- 2015
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In: Uppsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 120:4, s. 299-304
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Journal article (peer-reviewed)abstract
- Background. A 57-year old man with low-back pain was found to have a 3 x 3 x 3 cm presacral neuroendocrine tumour (NET) with widespread metastases, mainly to the skeleton. His neoplastic disease responded well to peptide receptor radionuclide therapy (PRRT) with the radiotagged somatostatin agonist Lu-177-DOTATATE. During almost 10 years he was fit for a normal life. He succumbed to an intraspinal dissemination. Procedures. A resection of the rectum, with a non-radical excision of the adjacent NET, was made. In addition to computerized tomography (CT), receptor positron emission tomography (PET) with Ga-68-labelled somatostatin analogues was used. Observations. The NET showed the growth pattern and immunoprofile of a G2 carcinoid. A majority cell population displayed immunoreactivity to ghrelin, exceptionally with co-immunoreactivity to motilin. Somatostatin receptor scintigraphy and Ga-68-DOTATATE PET-CT demonstrated uptake in the metastatic lesions. High serum concentrations of total (desacyl-)ghrelin were found with fluctuations reflecting the severity of the symptoms. In contrast, the concentrations of active (acyl-)ghrelin were consistently low, as were those of chromogranin A (CgA).Conclusions. Neoplastically transformed ghrelin cells can release large amounts of desacyl-ghrelin, evoking an array of non-specific clinical symptoms. Despite an early dissemination to the skeleton, a ghrelinoma can be compatible with longevity after adequate radiotherapy.
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| 5. |
- Hoppener, J. W. M., et al.
(author)
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Human Islet Amyloid Polypeptide Transgenic Mice: In Vivo and Ex Vivo Models for the Role of hIAPP in Type 2 Diabetes Mellitus
- 2008
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In: Experimental Diabetes Research. - : Hindawi Limited. - 1687-5214 .- 1687-5303.
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Journal article (peer-reviewed)abstract
- Human islet amyloid polypeptide (hIAPP), a pancreatic islet protein of 37 amino acids, is the main component of islet amyloid, seen at autopsy in patients with type 2 diabetes mellitus (DM2). To investigate the roles of hIAPP and islet amyloid in DM2, we generated transgenic mice expressing hIAPP in their islet beta cells. In this study, we found that after a long-term, high-fat diet challenge islet amyloid was observed in only 4 of 19 hIAPP transgenic mice. hIAPP transgenic females exhibited severe glucose intolerance, which was associated with a downregulation of GLUT-2 mRNA expression. In isolated islets from hIAPP males cultured for 3 weeks on high-glucose medium, the percentage of amyloid containing islets increased from 5.5% to 70%. This ex vivo system will allow a more rapid, convenient, and specific study of factors influencing islet amyloidosis as well as of therapeutic strategies to interfere with this pathological process. Copyright (C) 2008 J. W. M. Hoppener et al.
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| 6. |
- Mccourt, Andy, et al.
(author)
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Characterization of Gastric Mucosa Biopsies Reveals Alterations in Huntington's Disease.
- 2015
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In: PLoS Currents. - : Public Library of Science (PLoS). - 2157-3999. ; 7
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Journal article (peer-reviewed)abstract
- Weight loss is an important complication of Huntington's disease (HD), however the mechanism for weight loss in HD is not entirely understood. Mutant huntingtin is expressed in the gastrointestinal (GI) tract and, in HD mice, mutant huntingtin inclusions are found within the enteric nervous system along the GI tract. A reduction of neuropeptides, decreased mucosal thickness and villus length, as well as gut motility impairment, have also been shown in HD mice. We therefore set out to study gastric mucosa of patients with HD, looking for abnormalities of mucosal cells using immunohistochemistry. In order to investigate possible histological differences related to gastric acid production, we evaluated the cell density of acid producing parietal cells, as well as gastrin producing cells (the endocrine cell controlling parietal cell function). In addition, we looked at chief cells and somatostatin-containing cells. In gastric mucosa from HD subjects, compared to control subject biopsies, a reduced expression of gastrin (a marker of G cells) was found. This is in line with previous HD mouse studies showing reduction of GI tract neuropeptides.
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| 7. |
- van der Burg, Jorien m, et al.
(author)
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Gastrointestinal dysfunction contributes to weight loss in Huntington's disease mice.
- 2011
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In: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 44, s. 1-8
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Journal article (peer-reviewed)abstract
- Weight loss is the most important non-neurological complication of Huntington's disease (HD). It correlates with disease progression and affects the quality of life of HD patients, suggesting that it could be a valuable target for therapeutic intervention. The mechanism underlying weight loss in HD is unknown. Mutant huntingtin, the protein that causes the disease, is not only expressed in the brain, but also along the gastrointestinal (GI) tract. Here we demonstrate that the GI tract of HD mice is affected. At the anatomical level we observed loss of enteric neuropeptides, as well as decreased mucosal thickness and villus length. Exploring the functions of the GI system we found impaired gut motility, diarrhea, and malabsorption of food. The degree of malabsorption was inversely associated with body weight, suggesting that GI dysfunction plays an important role in weight loss in HD mice. In summary, these observations suggest that the GI tract is affected in HD mice and that GI dysfunction contributes to nutritional deficiencies and weight loss.
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| 8. |
- van der Burg, Jorien m, et al.
(author)
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Increased metabolism in the R6/2 mouse model of Huntington's disease.
- 2008
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In: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 29:1, s. 41-51
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Journal article (peer-reviewed)abstract
- Huntington’s disease (HD) is a hereditary disorder characterized by personality changes, chorea, dementia and weight loss. The cause of this weight loss is unknown. The aim of this study was to examine body weight changes and weight-regulating factors in HD using the R6/2 mouse model as a tool. We found that R6/2 mice started losing weight at 9 weeks of age. Total locomotor activity was unaltered and caloric intake was not decreased until 11 weeks of age, which led us to hypothesize that increased metabolism might underlie the weight loss. Indeed, oxygen consumption in R6/2 mice was elevated from 6 weeks of age, indicative of an increased metabolism. Several organ systems that regulate weight and metabolism, including the hypothalamus, the stomach and adipose tissue displayed abnormalities in R6/2 mice. Together, these data demonstrate that weight loss in R6/2 mice is associated with increased metabolism and changes in several weight-regulating factors.
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| 9. |
- Wierup, P, et al.
(author)
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Bronchial healing, lung parenchymal histology, and blood gases one month after transplantation of lungs topically cooled for 2 hours in the non-heart-beating cadaver
- 2000
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In: The Journal of Heart and Lung Transplantation. - 1557-3117. ; 19:3, s. 270-276
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Journal article (peer-reviewed)abstract
- BACKGROUND: The aim of this study was to investigate, in an experimental survival model, the functional and morphologic results of lung transplantation using lungs from non-heart-beating donors. METHODS: Left lungs, topically cooled to 25 degrees C for 2 hours in situ after 5 minutes of circulatory arrest followed by 26 minutes of unsuccessful cardiopulmonary resuscitation, were transplanted into syngeneic rats. Five weeks after the transplantation, right pneumonectomy was performed and blood gases measured after 60 minutes. In a control group, fresh donor lungs were used for transplantation and comparison was made with the cadaver group and a group of normal rats after right pneumonectomy. Morphologic changes were evaluated by semiquantitative scoring of 13 different parameters to obtain a total histologic index for each rat. RESULTS: Computerized tomography scans of the chest made during the third post-operative week showed normal lung parenchyma in both groups, and at 5 weeks there were no significant differences in blood gases. The bronchial anastomoses showed normal healing in all cases. The histologic changes in the lung parenchyma were generally mild and focal, primarily consisting of interstitial and perivascular mononuclear inflammation, bronchial inflammation and athelectasis. Surprisingly, the transplanted controls demonstrated the most pronounced changes, although only the difference in total histologic index between groups was significant. CONCLUSIONS: Lungs from non-heart-beating donors, topically cooled in the cadaver for two hours after failed resuscitation, showed normal bronchial healing and favorable parenchymal histology compared to transplanted control lungs 5 weeks after transplantation.
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| 10. |
- Wierup, P, et al.
(author)
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Ex vivo evaluation of nonacceptable donor lungs
- 2006
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In: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 81:2, s. 460-466
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Journal article (peer-reviewed)abstract
- Background. Only a minority of the potential candidates for lung donation are considered suitable, using current evaluation methods. A new method for ex vivo evaluation, with the potential for reconditioning of marginal and nonacceptable lungs, has been developed. This is a report of the ex vivo evaluation of six donor lungs deemed nonacceptable (arterial oxygen pressure less than 40 kPa) by the Scandiatransplant, Eurotransplant, and UK transplant organizations. Methods. The lungs are perfused ex vivo with Steen solution, a lung evaluation-preservation solution, mixed with red blood cells to a hematocrit of 15%. This extracellular solution is designed to have an optimal colloid osmotic pressure so that physiologic pressure and flow can be maintained without development of pulmonary edema. An oxygenator connected to the extracorporeal circuit maintains a normal mixed venous blood gas level in the perfusate. The lungs are ventilated and evaluated through analyses of pulmonary vascular resistance, oxygenation capacity, and arterial carbon dioxide pressure minus end-tidal carbon dioxide difference. Results. The arterial oxygen pressure (inspired oxygen fraction, 1.0) increased from 27 kPa (range, 17 to 34 kPa) in situ in the organ donor at the referring hospital to 57 kPa (range, 39 to 66 kPa) during the ex vivo evaluation. The pulmonary vascular resistance varied from 3.2 to 5.7 Wood units, and the arterial carbon dioxide pressure minus end-tidal carbon dioxide difference was in the range of 1 to 2.5 kPa. Conclusions. The arterial oxygen pressure improves significantly in this model. This ex vivo evaluation model is a valuable addition to the armamentarium in finding acceptable lungs in a donor population with inferior arterial oxygen pressure values.
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