| 1. |
- Amoroso, Matteo, 1984, et al.
(författare)
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Functional and morphological studies of in vivo vascularization of 3D-bioprinted human fat grafts
- 2021
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Ingår i: Bioprinting. - : Elsevier BV. - 2405-8866. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- Three-dimensional (3D) bioprinting offers the ability to design and biofabricate 3D structures based on autologous fat; however, the lack of vascularization in larger 3D-bioprinted constructs represents a limiting factor that hampers translation of this technology from bench to bedside. 3D bioprinting using microfractured fat mixed with nanocellulose–alginate hydrogel can promote vascularization through connections of fragments of vessels included in the fat. In this study, we determined the perfusion and diffusion characteristics of 3D-bioprinted fat constructs using magnetic resonance imaging (MRI) and assessed correlations between perfusion and angiogenesis within the printed constructs. Microfractured human fat from liposuction was printed with tunicate nanocellulose–alginate hydrogel, followed by transplantation of the constructs (10 × 10 × 3 mm) into nude mice that underwent longitudinal MRI for up to 99 days. Confirmation of vascularization was undertaken using immunohistochemical and histologic analyses. Before implantation, the constructs contained abundant fat tissue and fragments of human blood vessels (CD31+ and Ku80+), with subsequent in vivo MRI analysis following transplantation indicating low perfusion and suggesting their continued survival mainly by diffusion. Additionally, we observed a high diffusion coefficient (~2 × 10−3 mm2/s) that was preserved throughout the observation period. Following explantation, evaluation revealed that the constructs displayed preserved histology along with a mixture of human (Ku80+) and murine (Ku80−) erythrocyte-containing vessels. These results demonstrated successful interconnection of blood-vessel fragments from microfractured human fat via angiogenesis to form a vascular network with the host circulation, thereby confirming vascularization of the 3D-bioprinted fat constructs.
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| 2. |
- Kljajić, Marizela, et al.
(författare)
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Children Treated for Nonsyndromic Craniosynostosis Exhibit Average Adaptive Behavior Skills with Only Minor Shortcomings
- 2021
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Ingår i: Plastic and reconstructive surgery. - 1529-4242. ; 147:2, s. 453-464
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Tidskriftsartikel (refereegranskat)abstract
- Copyright © 2021 by the American Society of Plastic Surgeons. BACKGROUND: Adaptive behavior skills are important when assessing cognitive functions related to daily life; however, few studies have assessed these skills in patients treated for nonsyndromic craniosynostosis. In this study, the authors assessed the adaptive behavior skills of children treated for craniosynostosis and examined whether their outcomes are related to surgical technique. METHODS: The Adaptive Behavior Assessment System, 2nd Edition, parent report was used for children (age, 7 to 16 years) treated for sagittal (n = 41), metopic (n = 24), and other rare synostoses (n = 8). Background data, including intelligence quotient, were controlled for confounders. RESULTS: All evaluated children treated for craniosynostosis were estimated as lower in all aspects of adaptive behavior skills (full-scale, conceptual, social, and practical composites; effect size, 0.36 to 0.44) as compared with norms. The sagittal group showed shortcomings in social composite (effect size, 0.48) and subscales measuring self-care and self-direction, although no difference was observed between spring-assisted surgery and pi-plasty regarding outcomes of adaptive behavior skills. In addition, children treated for metopic synostosis showed results indicating shortcomings with adaptive behavior according to the full-scale, conceptual, and social composites (effect size, 0.53 to 0.61) relative to norms. Furthermore, attrition analysis revealed no significant differences between responders (rate, 80.2 percent) and nonresponders. CONCLUSION: These results found that children treated for craniosynostosis display average adaptive behavior skills, and that the two surgical techniques used to treat sagittal synostosis did not differ in their behavioral outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
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| 3. |
- Kölby, Lars, 1963, et al.
(författare)
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Histidine decarboxylase expression and histamine metabolism in gastric oxyntic mucosa during hypergastrinemia and carcinoid tumor formation.
- 1996
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Ingår i: Endocrinology. - 0013-7227. ; 137:10, s. 4435-42
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Tidskriftsartikel (refereegranskat)abstract
- Histamine is an important stimulator of gastric acid secretion. In experimental animals, inhibition of acid secretion by long term histamine2 receptor blockade causes hypergastrinemia, proliferation of enterochromaffin-like (ECL) cells, and formation of histamine-producing gastric carcinoids. The aim of this study was to examine the role of gastrin in histamine synthesis and metabolism of the oxyntic mucosa of normal, hyperplastic, and carcinoid-bearing Mastomys natalensis. Administration of exogenous gastrin to normal animals increased histidine decarboxylase (HDC) messenger RNA (mRNA) expression in the oxyntic mucosa within 30 min, indicating that gastrin stimulates histamine synthesis by regulating HDC mRNA abundance. Endogenous hypergastrinemia, induced by short term histamine2 receptor blockade (loxtidine) for 3-29 days, did not induce tumors, but enhanced the expression of HDC mRNA (2- to 4-fold elevated) and histamine contents (2-fold elevated) in the oxyntic mucosa. Long term histamine2 receptor blockade (7-21 months) resulted in sustained hypergastrinemia and ECL tumor formation. Tumor-bearing animals had a 4-fold increase in HDC mRNA expression and histamine contents of the oxyntic mucosa. Urinary excretion of the histamine metabolite methyl-imidazole-acetic acid was 2-fold elevated. Tumor-bearing animals recovering from histamine2 receptor blockade were normogastrinemic and had normal levels of HDC mRNA and histamine in the oxyntic mucosa as well as normal excretion of methyl-imidazole-acetic acid. The results indicate that ECL cell carcinoids developing during hypergastrinemia are well differentiated tumors that respond to high gastrin levels with increased histamine synthesis and secretion.
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| 4. |
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| 5. |
- Selvaggi, Gennaro, 1973, et al.
(författare)
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Ethical Considerations in Surgery for Single-suture Craniosynostosis.
- 2023
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Ingår i: The Journal of craniofacial surgery. - 1049-2275 .- 1536-3732. ; 34:7, s. 1922-1926
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Tidskriftsartikel (refereegranskat)abstract
- Single-suture craniosynostosis (SSC) describes the premature fusion of one cranial suture, which restricts cranial growth and consequently results in unaffected regions presenting a compensatory expansion. Surgery can redistribute intracranial volume, reduce the risk of elevated intracranial pressure, and improve head shape, potentially leading to improved neurocognitive function and social acceptance. However, there is limited evidence that surgery for SSC improves neurocognitive function and social acceptance. Given the inherent surgical risks and uncertainty of outcomes, the conditions under which this surgery should be allowed remain uncertain. Here, we discuss ethical questions regarding the permissibility of surgery, value of neurocognitive function and social acceptance, research ethics associated with SSC, patient autonomy and parental roles, and the process of recommending surgery and obtaining consent. Because surgery for SSC has become a routine procedure, its practice now presents a relatively low risk of complications. Furthermore, having acquired an understanding of the risks associated with this surgery, such knowledge fulfils the principle of non-maleficence although not beneficence. Thus, we advocate that surgery should only be offered within Institutional Review Board-approved research projects. In these situations, decisions concerning enrollment in scientific research involves health care providers and parents or guardians of the child, with the former acting as gate-keepers upon recognition of a lack of coping skills on the part of the parent or guardian in dealing with unforeseen outcomes. To minimize associated surgical risks and maximize its benefits, there exists a moral obligation to refer patients only to highly specialized centers.
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| 6. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Clinical management of gastric carcinoid tumors.
- 1994
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Ingår i: Digestion. - 0012-2823. ; 55 Suppl 3, s. 77-85
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Tidskriftsartikel (refereegranskat)abstract
- Four types of gastric carcinoids have been identified: (1) multiple small body-fundus carcinoids associated with chronic atrophic gastritis type A (A-CAG); (2) sporadic solitary lesions without specific pathogenetic background (non-A-CAG); (3) carcinoidosis associated with Zollinger-Ellison/MEN 1 syndrome, and (4) rare tumors, e.g. gastrin cell tumors, neuroendocrine carcinomas and mixed endocrine-exocrine tumors. In a retrospective study of 15 patients with gastric carcinoids (11 A-CAG, 3 non-A-CAG and 1 gastrin cell tumor) over a 10-year period, the histopathological and clinical features were assessed. The A-CAG-type carcinoids were clinically silent with lymph node metastases in 2/11 cases but no hepatic metastases. The non-A-CAG-type carcinoids were malignant with disseminated disease, hormonal symptoms and increased urinary excretion of the main histamine metabolite, MeImAA. Five patients with A-CAG tumors were subjected to antrectomy to remove hypergastrinemia, which is thought to be of pathogenetic importance for these tumors. During the observation period (1.5-8 years) 1 patient developed recurrent tumors, while the other 4 showed persistent argyrophil cell hyperplasia. A prospective treatment protocol of these tumors is suggested with endoscopic removal of less numerous, small lesions as first-step therapy, followed by antrectomy at recurrence. Larger lesions should be excised in combination with antrectomy. Gastrectomy is reserved for the rare cases of invasive tumors with lymph node metastases. As evident from the outcome of patients with non-A-CAG tumors radical surgery should be performed whenever practicable.
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| 7. |
- Andersson, Mattias K, 1979, et al.
(författare)
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Clinical, genetic and experimental studies of the Brooke-Spiegler (CYLD) skin tumor syndrome
- 2019
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Ingår i: Journal of Plastic Surgery and Hand Surgery. - : Medical Journals Sweden AB. - 2000-656X .- 2000-6764. ; 53:2, s. 71-75
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Tidskriftsartikel (refereegranskat)abstract
- Brooke-Spiegler syndrome (BSS; a.k.a. tuban tumor syndrome) is an autosomal dominant inherited skin disorder caused by germline mutations in the CYLD tumor suppressor gene. BSS is characterized by multiple skin adnexal tumors, mainly cylindromas and spiradenomas on the head and neck. The tumors are often severely disfiguring and require repeated surgical interventions. Here, we describe a four-generation BSS-family with a novel germline c.1613_1614delGC CYLD mutation that introduces a premature STOP codon predicted to result in a truncated, inactivated CYLD protein. In addition, we present a pilot study describing establishment of the first patient-derived xenografts (PDXs) from cutaneous CYLD-defective cylindromas. Fresh tumor tissues from cylindromas were transplanted into immunocompromised mice to generate PDXs. One xenograft showed progressive tumor growth after 3 months whereas the others remained unchanged in size during the 6 months study period. Histopathological and immunohistochemical analyses of the PDXs revealed that they recapitulate the histological and molecular features of their respective primary tumors, including expression of NTRK3 and the oncogenic driver MYB. In summary, we present the first preclinical BSS-model that morphologically and genetically recapitulates human CYLD-defective cylindromas. This model will be useful for preclinical therapeutic drug testing and for further studies of the molecular pathogenesis of inherited cylindromas.
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| 8. |
- Cornelissen, M. J., et al.
(författare)
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Perinatal complications in patients with unisutural craniosynostosis: An international multicentre retrospective cohort study
- 2017
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Ingår i: Journal of Cranio-Maxillofacial Surgery. - : Elsevier BV. - 1010-5182. ; 45:11, s. 1809-1814
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Craniosynostosis may lead to hampered fetal head molding and birth complications. To study the interaction between single suture craniosynostosis and delivery complications, an international, multicentre, retrospective cohort study was performed. Materials and methods: All infants born between 2006 and 2012 in the Netherlands and Sweden with sagittal or metopic suture synostosis were included. All births were included as a reference population. The primary outcome measure was rate of medically assisted labor. The secondary outcomes included method of conception, term of birth and fetal position. Results: We included 152 trigonocephaly patients, 272 scaphocephaly patients and 1.954.141 controls. A higher rate of assisted reproductive technology (ART) was found in patients with trigonocephaly (13%) and scaphocephaly (7%) compared to controls (3%, p < 0.001). Scaphocephaly resulted in more postterm births (8% vs 4%, p < 0.001). Trigonocephaly patients showed more preterm births (11% vs 6%, p < 0.001), breech position was more frequent (10% vs 4%, p = 0.003) and labor was more often induced. Rate of assisted delivery, including cesarean section, was significantly higher in both patient groups. Conclusions: Scaphocephaly leads to more postterm births and an increased rate of cesarean sections. Trigonocephaly is related to ART, and in addition higher rates of breech position and cesarean section are found. Prenatal detection of single suture craniosynostosis could improve perinatal care. (C) 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
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| 9. |
- Forssell-Aronsson, Eva, 1961, et al.
(författare)
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Aspects on radionuclide therapy in malignant pheochromocytomas.
- 2006
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923. ; 1073, s. 498-504
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Tidskriftsartikel (refereegranskat)abstract
- Malignant pheochromocytomas/paragangliomas (PCs/PGs) often have distant metastases to the skeleton, liver, and lungs. Radionuclide therapy is valuable for treatment of disseminated tumor disease and could be used as adjuvant therapy after surgery. Patients with local and/or distant metastases of PC/PG should be investigated preoperatively by scintigraphy using both 123I-MIBG and 111In-DTPA-D-Phe1-octreotide, to evaluate the possibilities for radionuclide therapy (i.e., a dosimetric estimation of radiation dose to the tumor tissue versus critical normal tissues). Individual patient dose-planning should be performed. For patients in whom positive therapeutic effects are anticipated radionuclide therapy can be applied. Therapy with both 131I-MIBG and 177Lu-octreotate might be favorable in individual patients with lesions visualized by both metaiodobenzylguanidine (MIBG) and octreotide scintigraphy with enhanced therapeutic effects and reduced side effects.
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| 10. |
- Jakobsen, A M, et al.
(författare)
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Differential expression of vesicular monoamine transporter (VMAT) 1 and 2 in gastrointestinal endocrine tumours.
- 2001
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Ingår i: The Journal of pathology. - : Wiley. - 0022-3417. ; 195:4, s. 463-72
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Tidskriftsartikel (refereegranskat)abstract
- Neuroendocrine tumours are characterized by their capacity to produce hormones, which are stored in vesicles and secretory granules. Demonstration of granule/vesicle proteins in tumours is taken as evidence of neuroendocrine differentiation. Vesicular monoamine transporters (VMAT1 and VMAT2) mediate the transport of amines into vesicles of neurons and endocrine cells. The expression of VMAT1 and VMAT2 and the usefulness of VMAT1 and VMAT2 in the histopathological diagnosis of gastrointestinal endocrine tumours have not been fully explored. This study therefore investigated the expression of VMAT1 and VMAT2 in 211 human gastrointestinal tumours by immunocytochemistry and western blotting. VMAT1 and/or VMAT2 were demonstrated in the majority of amine-producing endocrine tumours of gastric, ileal, and appendiceal origin. Serotonin-producing endocrine tumours (ileal and appendiceal carcinoids) expressed predominantly VMAT1, while histamine-producing endocrine tumours (gastric carcinoids) expressed VMAT2 almost exclusively. In peptide-producing endocrine tumours such as rectal carcinoids and endocrine pancreatic tumours, only a small number of immunopositive tumour cells were observed. No labelling was found in non-endocrine tumours, including gastric, colorectal and pancreatic adenocarcinomas and gastrointestinal stromal tumours. In conclusion, VMAT1 and VMAT2 are differentially expressed by gastrointestinal endocrine tumours, with a pattern specific for each tumour type, reflecting their neuroendocrine differentiation and origin. VMAT1 and VMAT2 may therefore become valuable markers in the classification of neuroendocrine tumours and may also indicate patients suitable for radioisotope treatment operating via these transporter systems.
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