| 1. |
- Andin, Ulla, et al.
(författare)
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Alzheimer's disease (AD) with and without white matter pathology-clinical identification of concurrent cardiovascular disorders.
- 2007
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Ingår i: Archives of Gerontology and Geriatrics. - : Elsevier BV. - 1872-6976 .- 0167-4943. ; 44, s. 277-286
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Tidskriftsartikel (refereegranskat)abstract
- Clinical vascular features, either as manifest vascular disease or as cardiovascular risk factors were compared in AD with and without neuropathological white matter disease (WMD). The aim of the study was to investigate whether the presence of WMD and the severity of either AD pathology or WMD were associated with different cardiovascular profiles. A total of 44 AD cases were retrospectively studied. All the cases were neuropathologically diagnosed as AD with WMD (n = 22) and as AD without WMD (n = 22), respectively. The patients' medical records were studied with regard to their medical history and to somatic and neurological findings including arrhythmia, congestive heart failure, angina, myocardial infarctions, signs of TIA/stroke, diabetes mellitus, and blood pressure abnormalities, such as hypertension and orthostatic hypotension. In AD-WMD, hypertension, orthostatic hypotension as well as dizziness/unsteadiness were significantly more common than in AD without WMD. Cardiovascular symptoms were more frequent in AD-WMD than in the other group, though the difference did not reach statistical significance. Hypothetically, abnormal and unstable blood pressure levels underlie recurrent cerebral hypoperfusion, which may in turn leave room for the development of WMD. Furthermore, dizziness/unsteadiness may be a symptom reflecting the presence of WMD. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
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| 2. |
- Angsten, Gertrud, et al.
(författare)
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Resolution of infantile intestinal pseudo-obstruction in a boy
- 2017
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Ingår i: Journal of Pediatric Surgery Case Reports. - : Elsevier. - 2213-5766. ; 24, s. 28-34
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Tidskriftsartikel (refereegranskat)abstract
- A term boy with spontaneous passage of meconium exhibited episodes of abdominal distension and diarrhea. Due to failure to thrive and suspicion of Hischsprung's disease he was referred to our university hospital at five months of age. Rectal biopsies were normal. Laparotomy revealed dilation of the small bowel and colon without any mechanical obstruction. Full thickness bowel biopsies were taken and a loop ileostomy was constructed. Histopathology revealed fibrosing myopathy, Cajal cell hypertrophy, and neuronal degeneration in both the large and small bowel. The small bowel showed mastocytosis without inflammation. A central venous catheter was placed for vascular access, replaced three times and later switched to a subcutaneous venous port. Catheters were locked after use with vancomycin-heparin and later taurolidine. The individually tailored home parenteral nutrition contained unsaturated fatty acid lipids to reduce cholestasis. Initial insufficient growth was improved after correction of partial parenteral nutrition based on a metabolic balance study. The ileostomy was revised once and finally taken down at 11 years of age following one year without parenteral support. At follow-up at 13 years of age he has episodes of moderate abdominal pain and has entered puberty and reports a high quality of life. (C) 2017 The Authors. Published by Elsevier Inc.
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| 3. |
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| 4. |
- Asif, Sana, et al.
(författare)
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Heparinization of cell surfaces with short peptide-conjugated PEG-lipid regulates thromboinflammation in transplantation of human MSCs and hepatocytes
- 2016
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 35, s. 194-205
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Tidskriftsartikel (refereegranskat)abstract
- Infusion of therapeutic cells into humans is associated with immune responses, including thromboinflammation, which result in a large loss of transplanted cells\ To address these problems, heparinization of the cell surfaces was achieved by a cell-surface modification technique using polyethylene glycol conjugated phospholipid (PEG-lipid) derivatives. A short heparin-binding peptide was conjugated to the PEG-lipid for immobilization of heparin conjugates on the surface of human mesenchymal stem cells (hMSCs) and human hepatocytes. Here three kinds of heparin-binding peptides were used for immobilizing heparin conjugates and examined for the antithrombogenic effects on the cell surface. The heparinized cells were incubated in human whole blood to evaluate their hemocompatibility by measuring blood parameters such as platelet count, coagulation markers, complement markers, and Factor Xa activity. We found that one of the heparin-binding peptides did not show cytotoxicity after the immobilization with heparin conjugates. The degree of binding of the heparin conjugates on the cell surface (analyzed by flow cytometer) depended on the ratio of the active peptide to control peptide. For both human MSCs and hepatocytes in whole-blood experiments, no platelet aggregation was seen in the heparin conjugate-immobilized cell group vs. the controls (non-coated cells or control peptide). Also, the levels of thrombin-antithrombin complex (TAT), C3a, and sC5b-9 were significantly lower than those of the controls, indicating a lower activation of coagulation and complement. Factor Xa analysis indicated that the heparin conjugate was still active on the cell surface at 24 h post-coating. It is possible to immobilize heparin conjugates onto hMSC and human hepatocyte surfaces and thereby protect the cell surfaces from damaging thromboinflammation. Statement of Signigficance We present a promising approach to enhance the biocompatibility of therapeutic cells. Here we used short peptide-conjugated PEG-lipid for cell surface modification and heparin conjugates for the coating of human hepatocytes and MSCs. We screened the short peptides to find higher affinity for heparinization of cell surface and performed hemocompatibility assay of heparinized human hepatocytes and human MSCs in human whole blood. Using heparin-binding peptide with higher affinity, not only coagulation activation but also complement activation was significantly suppressed. Thus, it was possible to protect human hepatocytes and human MSCs from the attack of thromboinflammatory activation, which can contribute to the improvement graft survival. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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| 5. |
- Brunnström, Hans, et al.
(författare)
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History of depression prior to Alzheimer's disease and vascular dementia verified post-mortem.
- 2013
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Ingår i: Archives of Gerontology and Geriatrics. - : Elsevier BV. - 1872-6976 .- 0167-4943. ; 56:1, s. 80-84
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to analyze the medical history, with regards to previous remote depression, in patients with neuropathologically verified Alzheimer's disease (AD), vascular dementia (VaD) and mixed AD/VaD. The 201 patients included (115 AD, 44 VaD and 42 mixed AD/VaD) had been referred to the Psychogeriatric/Psychiatric Department, Lund University Hospital, for psychogeriatric investigation and were followed-up with clinical records and detailed information on psychiatric history prior to the onset of dementia. Depression was considered to exist when the patient had consulted a psychiatrist or physician and had been diagnosed with a "depressive episode" or "depression" and when anti-depressants and/or other specific treatments had been prescribed. Twenty patients (10%) had suffered from depression earlier in life well before the onset of dementia. Eight of the 9 AD patients with a previous diagnosis of depression had suffered from only one depressive episode and all had responded well to treatment, with complete recovery. In the VaD group, 8 out of 9 patients suffered two or more depressive episodes and only two recovered completely. Events with a possible significant relationship to depression were seen in 8 of the 9 AD patients but in only 1 of the 9 VaD patients. Psychotic symptoms were more common in VaD than in the AD group. The treatment modality of depression was similar in the groups. In conclusion, a history of depression prior to dementia is more common and more therapy-resistant in VaD than in AD.
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| 6. |
- Brunnström, Hans, et al.
(författare)
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Prevalence of dementia subtypes: A 30-year retrospective survey of neuropathological reports.
- 2009
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Ingår i: Archives of Gerontology and Geriatrics. - : Elsevier BV. - 1872-6976 .- 0167-4943. ; Aug 7, s. 146-149
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the distribution of neuropathologically defined dementia subtypes among individuals with dementia disorder. The neuropathological reports were studied on all patients (n=524; 55.3% females; median age 80, range 39-102 years) with clinically diagnosed dementia disorder who underwent complete autopsy including neuropathological examination within the Department of Pathology at the University Hospital in Lund, Sweden, during the years 1974-2004. The neuropathological diagnosis was Alzheimer's disease (AD) in 42.0% of the cases, vascular dementia (VaD) in 23.7%, dementia of combined Alzheimer and vascular pathology in 21.6%, and frontotemporal dementia in 4.0% of the patients. The remaining 8.8% of the patients had other dementia disorders, including combinations other than combined Alzheimer and vascular pathology. The registered prevalence of dementia subtypes depends on many variables, including referral habits, clinical and neuropathological judgments and diagnostic traditions, all of these variables potentially changing over time. This, however, does not seem to obscure the delineation of the major dementia subgroups. In this material of 30 years from Lund in the south of Sweden, AD by far dominated among dementia subtypes, while cerebrovascular pathology corresponded with the dementia disorder, either entirely or partly, in almost half of the demented patients.
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| 7. |
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| 8. |
- Donoso, Felipe, et al.
(författare)
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Outcome and management in infants with esophageal atresia : a single centre observational study
- 2016
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Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 51:9, s. 1421-1425
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Tidskriftsartikel (refereegranskat)abstract
- Background/Purpose: A successful outcome in the repair of esophageal atresia (EA) is associated with a high quality pediatric surgical centre, however there are several controversies regarding the optimal management. The aim of this study was to investigate the outcome and management EA in a single pediatric surgical centre.Methods: Medical records of infants with repaired EA from 1994 to 2013 were reviewed.Results: 129 infants were included. Median follow-up was 5.3 (range 0.1-21) years. Overall survival was 94.6%, incidences of anastomotic leakage 7.0%, recurrent fistula 4.6% and anastomotic stricture 53.5% (36.2% within first year). In long gap EA (n = 13), delayed primary anastomosis was performed in 9 (69.2%), gastric tube in 3 (23.1%) and gastric transposition in one (7.7%) infants. The incidences of anastomotic leakage and stricture in long gap EA were, 23.1% and 69.2%, respectively. Peroperative tracheobronchoscopy and postoperative esophagography were implemented as a routine during the study-period, but chest drains were routinely abandoned.Conclusion: The outcome in this study is fully comparable with recent international reports showing a low mortality but a significant morbidity, especially considering anastomotic strictures and LGEA. Multicenter EA registry with long-term follow up may help to establish best management of EA.
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| 9. |
- Englund, Elisabet, et al.
(författare)
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Familial Lund frontotemporal dementia caused by C9ORF72 hexanucleotide expansion.
- 2012
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 1558-1497 .- 0197-4580.
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) as an important clinical entity was rediscovered in Lund and Manchester in the early 1990s. Here we show that the large Lund pedigree with behavioral variant of frontotemporal dementia previously described with this disorder has an expansion in the recently described C9ORF72 locus on chromosome 9.
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| 10. |
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| 11. |
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| 12. |
- Gustafson-Capková, Sofia, 1964-
(författare)
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Integrating Prosody into an Account of Discourse Structure
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis a study of discourse segmenting is carried out, which investigates both segment boundaries and segment content. The results are related to discourse theory. We study the questions of how the prosody and the text structure influence subjects' annotations of discourse boundaries and discourse prominence. The hypothesis was that the annotations would be influenced by the discourse type.Two studies were carried out. 1) a study of boundary annotation, 2) a study of prominence annotation. All studies were made on four different discourse types, scripted and spontaneous monologue and scripted and spontaneous dialogue. In addition the annotations were carried out under two different conditions 1) based on transcripts alone and 2) based on transcripts together with access to the speech signal.The results indicate that the boundary annotations were less dependent on the speech signal than the prominence annotations. It seems that subjects have segmented on the basis of the text structure, while prominence to a great extent was annotated on the basis of the prosody. In the case of boundary markings the boundary context in terms of parts of speech differs across speaking styles, which is not the case for the prominences. A separate study of segment intentions was also made, and it was found that the interpretation of a specific intention, questions, seems to be arrived at primarily on the basis of the text structure. However, in some cases also the prosody affects the annotations.The picture that emerges indicates a distribution of labour between text structure and prosody, governed by the principle of economy. In cases where the boundaries were less well definied, as in e.g. spontaneous monologue, the pattern of the prominences was clearer. In cases where the boundaries were more clearly indicated, as in read aloud text, the prominences were less clearly communicated.The findings were interpreted within Grosz and Sidner's (1986) discourse theory. It is suggested that differences in the segmenting strategy originating from the interaction of text structure and prosody can be expressed as differences in the contributions from the different components of discourse suggested in the framework of Grosz and Sidner (1986).
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| 13. |
- Gustafson, D, et al.
(författare)
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An 18-year follow-up of overweight and risk of Alzheimer disease
- 2003
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Ingår i: Archives of Internal Medicine. - 0003-9926 .- 1538-3679. ; 163:13, s. 1524-1528
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Tidskriftsartikel (refereegranskat)abstract
- Background Overweight and obesity are epidemic in Western societies and constitute a major public health problem because of adverse effects on vascular health. Vascular factors may play a role in the development of a rapidly growing disease of late life, Alzheimer disease (AD). Using body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters), we examined whether overweight is a risk factor for dementia and AD.Methods The relationship between BMI and dementia risk was investigated in a representative cohort of 392 nondemented Swedish adults who were followed up from age 70 to 88 years, with the use of neuropsychiatric, anthropometric, and other measurements. Multivariate Cox proportional hazards regression analyses included BMI, blood pressure, cardiovascular disease, cigarette smoking, socioeconomic status, and treatment for hypertension.Results: During the 18-year follow-up (4184.8 risk-years), 93 participants were diagnosed as having dementia. Women who developed dementia between ages 79 and 88 years were overweight, with a higher average BMI at age 70 years (27.7 vs 25.7; P = .007), 75 years (27.9 vs 25.0; P<.001), and 79 years (26.9 vs 25.1; P = .02) compared with nondemented women. A higher degree of overweight was observed in women who developed AD at 70 years (29.3; P = .009), 75 years (29.6; P<.001), and 79 years (28.2; P = .003) compared with nondemented women. For every 1.0 increase in BMI at age 70 years, AD risk increased by 36%. These associations were not found in men.Conclusions Overweight is epidemic in Western societies. Our data suggest that overweight at high ages is a risk factor for dementia, particularly AD, in women. This may have profound implications for dementia prevention.
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| 14. |
- Gustafson, Elisabet, et al.
(författare)
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Control of IBMIR Induced by Fresh and Cryopreserved Hepatocytes by Low Molecular Weight Dextran Sulfate Versus Heparin
- 2017
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Ingår i: Cell Transplantation. - : Sage Publications. - 0963-6897 .- 1555-3892. ; 26:1, s. 71-81
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Tidskriftsartikel (refereegranskat)abstract
- Rapid destruction of hepatocytes after hepatocyte transplantation has hampered the application of this procedure clinically. The instant blood-mediated inflammatory reaction (IBMIR) is a plausible underlying cause for this cell loss. The present study was designed to evaluate the capacity of low molecular weight dextran sulfate (LMW-DS) to control these initial reactions from the innate immune system. Fresh and cryopreserved hepatocytes were tested in an in vitro whole-blood model using ABO-compatible blood. The ability to elicit IBMIR and the capacity of LMW-DS (100 mu g/ml) to attenuate the degree of activation of the cascade systems were monitored. The effect was also compared to conventional anticoagulant therapy using unfractionated heparin (1 IU/ml). Both fresh and freeze thawed hepatocytes elicited IBMIR to the same extent. LMW-DS reduced the platelet loss and maintained the cell counts at the same degree as unfractionated heparin, but controlled the coagulation and complement systems significantly more efficiently than heparin. LMW-DS also attenuated the IBMIR elicited by freeze thawed cells. Therefore, LMW-DS inhibits the cascade systems and maintains the cell counts in blood triggered by both fresh and cryopreserved hepatocytes in direct contact with ABO-matched blood. LMW-DS at a previously used and clinically applicable concentration (100 mu g/ml) inhibits IBMIR in vitro and is therefore a potential IBMIR inhibitor in hepatocyte transplantation.
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| 15. |
- Gustafson, Elisabet K., et al.
(författare)
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Controlled outcome of Hirschsprung's disease beyond adolescence : a single center experience
- 2019
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Ingår i: Pediatric surgery international (Print). - : Springer. - 0179-0358 .- 1437-9813. ; 35:2, s. 181-185
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe aim of this study was to assess the function and quality of life of Hirschsprung's Disease (HD) beyond adolescence and relate it to matched controls.MethodsAll 203 patients diagnosed with HD at our department from 1961 to 1995 were identified. 21 had died, 43 had unclear diagnosis and 16 could not be traced. The remaining 123 patients were sent bowel function and SF-36 quality of life questionnaires. 69 patients (mean age 37.8, range 22-58, 13 female) responded and were matched with 138 age and sex-matched controls.ResultsFunction: HD-patients had significantly higher number of bowel movements per week, higher incidence of soiling, urgency, permanent stomas, use of laxatives, enemas and loperamide. HD-patients also scored significantly lower in their satisfaction with their bowel function. There was, however, no significant difference in Miller Incontinence score.QOL: HD-patients reported a significantly higher incidence of negative impact by their bowel function on daily life, social interaction and ability to go on vacation. There were no significant differences in SF-36-scores.ConclusionsBowel function has a lifelong negative impact on the lives of patients with HD. This strongly indicates a need for structured follow-up beyond adolescence.
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| 16. |
- Gustafson, Elisabet K., et al.
(författare)
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Exposure of von Willebrand Factor on Isolated Hepatocytes Promotes Tethering of Platelets to the Cell Surface
- 2019
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Ingår i: Transplantation. - : Wolters Kluwer. - 0041-1337 .- 1534-6080. ; 103:8, s. 1630-1638
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Tidskriftsartikel (refereegranskat)abstract
- Background. Hepatocyte transplantation (Hctx) is a potentially attractive method for the treatment of acute liver failure and liver-based metabolic disorders. Unfortunately, the procedure is hampered by the instant blood-mediated inflammatory reaction (IBMIR), a thromboinflammatory response elicited by the vascular innate immune system, causing activation of the coagulation and complement systems and clearance of transplanted cells. Observations have also revealed platelets adhered to the surface of the hepatocytes (Hc). To establish Hctx as a clinical treatment, all factors that trigger IBMIR need to be identified and controlled. This work explores the expression of von Willebrand factor (VWF) on isolated Hc resulting in tethering of platelets. Methods. VWF on Hc was studied by flow cytometry, confocal microscopy, immunoblot, and real-time polymerase chain reaction. Interaction between Hc and platelets was studied in a Chandler loop model. Adhesion of platelets to the hepatocyte surface was demonstrated by flow cytometry and confocal microscopy. Results. Isolated Hc constitutively express VWF on their cell surface and mRNA for VWF was found in the cells. Hc and platelets, independently of coagulation formed complexes, were shown by antibody blocking studies to be dependent on hepatocyte-associated VWF and platelet-bound glycoprotein Ib alpha. Conclusions. VWF on isolated Hc causes, in contact with blood, adhesion of platelets, which thereby forms an ideal surface for coagulation. This phenomenon needs to be considered in hepatocyte-based reconstitution therapy and possibly even in other settings of cell transplantation.
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| 17. |
- Gustafson, Elisabet K., et al.
(författare)
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The Instant Blood-Mediated Inflammatory Reaction Characterized in Hepatocyte Transplantation
- 2011
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 91:6, s. 632-638
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Tidskriftsartikel (refereegranskat)abstract
- Background. Hepatocyte transplantation (HcTx) has proven to be a safe procedure, although the functional results have been unsatisfactory, probably due to insufficient engraftment or a loss of transplanted mass or function. In this study, we investigate whether hepatocytes in contact with blood induce an inflammatory reaction leading to, similar to what happens in clinical islet transplantation, an instant blood-mediated inflammatory reaction (IBMIR) resulting in an early loss of transplanted cells. Methods. By using an experimental model that mimics the portal vein blood flow, we could study different parameters reflecting the effects on the innate immunity elicited by hepatocytes in contact with ABO-matched human blood. Results. We report that all aspects of the IBMIR such as platelet and granulocyte consumption, coagulation, and complement activation were demonstrated. Addition of various specific inhibitors of coagulation allowed us to clearly delineate the various stages of the hepatocyte-triggered IBMIR and show that the reaction was triggered by tissue factor. Analysis of a case of clinical HcTx showed that hepatocyte-induced IBMIR also occurs in vivo. Both the inflammatory and the coagulation aspects were controlled by low-molecular-weight dextran sulfate. Conclusion. Isolated hepatocytes in contact with blood induce the IBMIR in vitro, and there are indications that these events are also relevant in vivo. According to these findings, HcTx would benefit from controlling a wider range of signals from the innate immune system.
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| 18. |
- Gustafson, Elisabet
(författare)
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Thromboinflammation : in a Model of Hepatocyte Transplantation
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hepatocyte transplantation is an attractive method for the treatment of metabolic liver disease and acute liver failure. The clinical application of this method has been hampered by a large initial loss of transplanted cells.This thesis has identified and characterized an instant blood-mediated inflammatory reaction (IBMIR), which is a thromboinflammatory response from the innate immunity that may partly explain the observed loss of cells. In vitro perifusion experiments were performed and established that hepatocytes in contact with blood activate the complement and coagulation systems and induce clot formation in conjunction with the recruitment of neutrophils. Within an hour, the hepatocytes were surrounded by platelets and entrapped in a clot infiltrated by neutrophils. Furthermore, hepatocytes expressed tissue factor (TF), and the reactions were shown to be initiated through the TF pathway. Monitoring of hepatocyte transplantation in vivo revealed activation of the same parameters as were noted in vitro.For the first time, von Willebrand factor (vWF) was identified on the hepatocyte surface, being demonstrated by flow cytometry and confocal microscopy. mRNA for vWF was also confirmed in hepatocytes. Complex formation between platelets and hepatocytes was also identified. Addition of antibodies targeting the binding site for vWF on the platelets reduced the complex formation.Two different strategies, systemic and local intervention, were applied to diminish the thromboinflammation elicited from the hepatocytes in contact with ABO-matched blood. Systemic inhibition with LMW-DS, in a clinically applicable dose, was found to be superior in controlling the IBMIR in vitro when compared to heparin. Cryopreserved hepatocytes elicited the IBMIR to the same extent as did fresh hepatocytes, and the IBMIR was equally well controlled with LMW-DS in both cryopreserved and fresh cells.Hepatocytes were coated with two layers of immobilized heparin in an attempt to protect the cells from the IBMIR. In vitro perifusion experiments showed heparinized hepatocytes triggered a significantly lower degree of IBMIR.
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| 19. |
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| 20. |
- Gustafson, Lars, et al.
(författare)
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A 50-year perspective of a family with chromosome 14-linked Alzheimer’s disease
- 1998
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 1432-1203 .- 0340-6717. ; 102:3, s. 253-257
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Tidskriftsartikel (refereegranskat)abstract
- A Swedish family with two generations suffering from presenile dementia with an unusually severe Alzheimer encephalopathy was first reported in 1946. The hypothesis that the disease was inherited through a dominant gene is strongly supported by the follow-up 50years later of three additional generations and molecular genetic findings of a novel presenilin-1 gene mutation in the family. The pedigree contains six cases with well-documented dementia in four consecutive generations. The Alzheimer encephalopathy was unusually severe in the three cases studied post-mortem, with a pronounced involvement of the central grey structures, such as the claustrum, the nuclei around the third ventricle, the central thalamic nuclei and the brain stem. There were no vascular lesions and little amyloid angiopathy. All six affected cases showed the typical temporoparietal symptom pattern and other core symptoms of Alzheimer’s disease, such as logoclonia, myoclonic twitchings and major motor seizures. Other predominant features were psychomotor slowness, increased muscular tension, a stiff stooped gait and a rapid loss of weight. The symptom pattern is convincingly explained by the consistent and severe involvement of cortical and central grey structures and is probably linked to the presenilin-1 gene mutation.
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| 21. |
- Gustafson, Lars, et al.
(författare)
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A factor analytic approach to symptom patterns in dementia.
- 2010
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Ingår i: International Journal of Alzheimer's Disease. - : Hindawi Limited. - 2090-0252 .- 2090-8024.
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Tidskriftsartikel (refereegranskat)abstract
- Previous publications have shown a high diagnostic sensitivity and specificity of three short clinical rating scales for Alzheimer's disease (AD), frontotemporal dementia (FTD), and vascular dementia (VaD) validated against neuropathological (NP) diagnoses. In this study, the aim was to perform an exploratory factor analysis of the items in these clinical rating scales. The study included 190 patients with postmortem diagnoses of AD (n = 74), VaD (n = 33), mixed AD/VaD (n = 31), or FTD (n = 52). The factor analysis produced three strong factors. Factor 1 contained items describing cerebrovascular disease, similar to the Hachinski Ischemic Score. Factor 2 enclosed major clinical characteristics of FTD, and factor 3 showed a striking similarity to the AD scale. A fourth symptom cluster was described by perception and expression of emotions. The factor analyses strongly support the construct validity of the diagnostic rating scales.
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| 22. |
- Gustafson, Lars, et al.
(författare)
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The accuracy of short clinical rating scales in neuropathologically diagnosed dementia.
- 2010
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Ingår i: The American journal of geriatric psychiatry. - 1064-7481 .- 1545-7214. ; 18:9, s. 810-820
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The overall aim was to evaluate to what extent the diagnosis of dementia subtypes, obtained by three clinical rating scales, concurred with postmortem neuropathologic (NP) diagnosis of Alzheimer disease (AD), frontotemporal dementia (FTD), vascular dementia (VaD) and mixed AD/VaD. Design: A prospective longitudinal clinical work-up with postmortem NP examination. Participants: Two hundred nine patients with dementia referred for clinical evaluation and follow-up. Methods: The diagnostic scores in a set of three short clinical rating scales for AD, FTD, and VaD were evaluated against NP diagnoses. Results: The sensitivity and specificity of the AD scale were 0.80 and 0.87, respectively, of the FTD scale 0.93 and 0.92, respectively, and of the Hachinski Ischemic Score (HIS, VaD diagnosis) 0.69 and 0.92, respectively. Cases with mixed AD/VaD generally presented a combination of high AD and ischemic scores. A preferred cutoff score of six was identified for both the AD and FTD scales. Conclusions: All three clinical rating scales showed a high sensitivity and specificity, in close agreement with final NP diagnosis-for the HIS a moderate sensitivity. These scales may thus be considered good diagnostic tools and are recommended for clinical and research center settings.
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| 23. |
- Jedel, Elizabeth, 1962, et al.
(författare)
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Anxiety and depression symptoms in women with polycystic ovary syndrome compared with controls matched for body mass index.
- 2010
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Ingår i: Human reproduction. - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 25:2, s. 450-456
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Anxiety and depression are more prevalent in women with polycystic ovary syndrome (PCOS) than in those without this disorder. Possible confounding effects of overweight and obesity are suggested. The aim was to compare symptoms of anxiety and depression in women with PCOS and controls matched for age, body weight and body mass index (BMI). METHODS Women with PCOS (n = 30) and controls (n = 30) were recruited from the community. Persons with ongoing psychotropic medication were excluded. All potential participants underwent gynecological examination to confirm case-control status. Participants completed the self-reported versions of the Brief Scale for Anxiety (BSA-S) and Montgomery Asberg Depression Rating Scale (MADRS-S). RESULTS Women with PCOS had a higher BSA-S score compared with controls (median, range: 10.5, 1-24 versus 5.0, 0-28, P < 0.001). They scored higher on the following four individual symptoms: reduced sleep (2.0, 0-5 versus 0, 0-2, P < 0.001), worry (1.5, 0-4 versus 0, 0-6, P = 0.004), phobias (1, 0-4 versus 0, 0-3, P < 0.001), and pain (1, 0-3 versus 0, 0-2, P < 0.001). No statistical difference was demonstrated regarding MADRS-S scores (10.0, 0-27 versus 5.5, 0-24, P = 0.053). Only one of the nine MADRS-S symptoms, reduced sleep, which is also included in the BSA-S, differed between cases and controls. CONCLUSIONS Several anxiety symptoms distinguished women with PCOS from a control group matched on BMI. A better understanding of the symptoms is needed to identify and alleviate anxiety symptoms in this vulnerable group.
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| 24. |
- Jedel, Elizabeth, 1962, et al.
(författare)
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Sex steroids, insulin sensitivity and sympathetic nerve activity in relation to affective symptoms in women with polycystic ovary syndrome.
- 2011
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 36:10, s. 1470-9
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Affective symptoms are poorly understood in polycystic ovary syndrome (PCOS). Clinical signs of hyperandrogenism and high serum androgens are key features in PCOS, and women with PCOS are more likely to be overweight or obese, as well as insulin resistant. Further, PCOS is associated with high sympathetic nerve activity. OBJECTIVE: To elucidate if self-reported hirsutism, body mass index (BMI) and waistline, circulating sex steroids, sex hormone-binding globulin (SHBG), insulin sensitivity and sympathetic nerve activity are associated with depression and anxiety-related symptoms in women with PCOS. DESIGN AND METHODS: Seventy-two women with PCOS, aged 21-37 years, were recruited from the community. Hirsutism was self-reported using the Ferriman-Gallway score. Serum estrogens, sex steroid precursors, androgens and glucuronidated androgen metabolites were analyzed by gas and liquid chromatography/mass spectroscopy (GC-MS/LC-MS/MS) and SHBG by chemiluminiscent microparticle immunoassay (CMIA). Insulin sensitivity was measured with euglycemic hyperinsulinemic clamp. Sympathetic nerve activity was measured with microneurography. Symptoms of depression and anxiety were self-reported using the Montgomery Åsberg Depression Rating Scale (MADRS-S) and the Brief Scale for Anxiety (BSA-S). RESULTS: Circulating concentrations of testosterone (T) (P=0.026), free T (FT) (P=0.025), and androstane-3α 17β-diol-3glucuronide (3G) (P=0.029) were lower in women with depression symptoms of potential clinical relevance (MADR-S≥11). The odds of having a MADRS-S score ≥11 were higher with lower FT and 3G. No associations with BSA-S were noted. CONCLUSION: Lower circulating FT and 3G were associated with worse self-reported depression symptoms. The relationship between mental health, sex steroids and corresponding metabolites in PCOS requires further investigation.
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| 25. |
- Klar, Joakim, et al.
(författare)
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Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution
- 2015
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Ingår i: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 23:12, s. 1679-1683
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Tidskriftsartikel (refereegranskat)abstract
- Familial visceral myopathy (FVM) is a rare heritable and heterogeneous condition due to impaired smooth muscle function. We identified a family segregating 11 individuals with a spectrum of visceral symptoms involving the small intestine, colon, biliary tract, urinary tract and uterus. Whole-exome sequencing revealed a novel heterozygous tandem base substitution c.806_807delinsAA (p.(Gly269Glu)) in ACTG2, encoding smooth muscle actin gamma-2, in affected family members. Variants in ACTG2 were recently identified in FVM with intestinal pseudo-obstruction as well as with the congenital megacystics-microcolon-intestinal hypoperistalsis syndrome. In our family, eight affected members presented with severe complications from the biliary and/or the urinary tracts in addition to gastrointestinal pseudo-obstructions. Furthermore, all affected mothers had a history of assisted deliveries owing to poor progress during labor and weak uterine contractions. The variable involvement of multiple smooth muscle-dependent organs in our family, including the biliary tract and the uterus, add to the phenotypic spectrum associated with ACTG2 missense variants.
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| 26. |
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| 27. |
- Landqvist, Maria, et al.
(författare)
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Psychotic symptoms in frontotemporal dementia: a diagnostic dilemma?
- 2015
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Ingår i: International Psychogeriatrics. - 1741-203X. ; 27:4, s. 531-539
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT Background: Frontotemporal dementia (FTD) constitutes a spectrum of neurodegenerative disorders associated with degeneration of, predominantly, the frontal and temporal lobes. The clinical heterogeneity is evident, and early diagnosis is a challenge. The primary objectives were to characterize psychotic symptoms, initial clinical diagnoses and family history in neuropathologically verified FTD-patients and to analyze possible correlations with different neuropathological findings. Methods: The medical records of 97 consecutive patients with a neuropathological diagnosis of frontotemporal lobar degeneration (FTLD) were reevaluated. Psychotic symptoms (hallucinations, delusions, paranoid ideas), initial diagnosis and family history for psychiatric disorders were analyzed. Results: Psychotic symptoms were present in 31 patients (32%). There were no significant differences in age at onset, disease duration or gender between patients with and without psychotic symptoms. Paranoid ideas were seen in 20.6%, and hallucinations and delusions in 17.5% in equal measure. Apart from a strong correlation between psychotic symptoms and predominantly right-sided brain degeneration, the majority of patients (77.4%) were tau-negative. Only 14.4% of the patients were initially diagnosed as FTD, while other types of dementia were seen in 34%, other psychiatric disorders in 42%, and 9.2% with other cognitive/neurological disorders. The patients who were initially diagnosed with a psychiatric disorder were significantly younger than the patients with other initial clinical diagnoses. A positive heredity for dementia or other psychiatric disorder was seen in 42% and 26% of the patients respectively. Conclusions: Psychotic symptoms, not covered by current diagnostic criteria, are common and may lead to clinical misdiagnosis in FTD.
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| 28. |
- Landqvist, Maria, et al.
(författare)
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Somatic complaints in frontotemporal dementia.
- 2014
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Ingår i: American Journal of Neurodegenerative Disease. - 2165-591X. ; 3:2, s. 84-92
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is associated with a broad spectrum of clinical characteristics. The objective of this study was to analyze the prevalence of unexplained somatic complaints in neuropathologically verified FTD. We also examined whether the somatic presentations correlated with protein pathology or regional brain pathology and if the patients with these somatic features showed more depressive traits. Ninety-seven consecutively neuropathologically verified FTLD patients were selected. All 97 patients were part of a longitudinal study of FTD and all medical records were systematically reviewed. The somatic complaints focused on were headache, musculoskeletal, gastro/urogenital and abnormal pain response. Symptoms of somatic character (either somatic complaints and/or abnormal pain response) were found in 40.2%. These patients did not differ from the total group with regard to gender, age at onset or duration. Six patients showed exaggerated reactions to sensory stimuli, whereas three patients showed reduced response to pain. Depressive traits were present in 38% and did not correlate with somatic complaints. Suicidal behavior was present in 17 patients, in 10 of these suicidal behavior was concurrent with somatic complaints. No clear correlation between somatic complaints and brain protein pathology, regional pathology or asymmetric hemispherical atrophy was found. Our results show that many FTD patients suffer from unexplained somatic complaints before and/or during dementia where no clear correlation can be found with protein pathology or regional degeneration. Somatic complaints are not covered by current diagnostic criteria for FTD, but need to be considered in diagnostics and care. The need for prospective studies with neuropathological follow up must be stressed as these phenomena remain unexplained, misinterpreted, bizarre and, in many cases, excruciating.
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| 29. |
- Larsson, Elna-Marie, et al.
(författare)
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Magnetic resonance imaging and histopathology in dementia, clinically of frontotemporal type
- 2000
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 11:3, s. 123-134
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Tidskriftsartikel (refereegranskat)abstract
- The magnetic resonance imaging (MRI) and computed tomography findings in 28 patients with the clinical diagnosis of frontotemporal dementia (FTD) were compared with the findings in a control group of 76 individuals without dementia or stroke. A pattern of frontal and temporal atrophy with predominantly frontal white matter changes was found in the FTD patients, and this was significantly different from the radiological findings in the control group. Six of the FTD patients have undergone autopsy. Histopathological evaluation showed a primary cortical degenerative disease (frontal lobe degeneration of non-Alzheimer type) in 3 of them, and primary white matter disorder, mainly frontal, of basically ischemic type (selective incomplete white matter infarction) in 3 of them. MRI could be a helpful tool to support the clinical diagnosis FTD, especially in young patients. MRI may also be helpful for the differentiation of a primary neurodegenerative from a mainly ischemic-vascular type of dementia.
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| 30. |
- Leja, Justyna, et al.
(författare)
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A novel chromogranin-A promoter-driven oncolytic adenovirus for midgut carcinoid therapy
- 2007
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:8, s. 2455-2462
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The use of replication-selective oncolytic adenoviruses is an emerging therapeutic approach for cancer, which thus far has not been employed for carcinoids. We therefore constructed Ad[CgA-E1A], a novel replication-selective oncolytic adenovirus, where the chromogranin A (CgA) promoter controls expression of the adenoviral E1A gene. Experimental Design: The Ad[CgA-E1A] virus was evaluated for E1A protein expression, replication ability, and cytolytic activity in various cell lines. It was also evaluated for treatment of xenografted human carcinoid tumors in nude mice. To use Ad[CgA-E1A] for the treatment of carcinoid liver metastases, it is important that normal hepatocytes do not support virus replication to minimize hepatotoxicity. We therefore evaluated CgA protein expression in normal hepatocytes. We also evaluated CgA gene expression in normal hepatocytes and microdissected tumor cells from carcinoid metastases. Results: We found that Ad[CgA-E1A] replicates similarly to wild-type virus in tumor cells with neuroendocrine features, including the BON carcinoid cell line and the SH-SY-5Y neuroblastoma cell lines, whereas it is attenuated in other cell types. Thus, cells where the CgA promoter is active are selectively killed. We also found that Ad[CgA-E1A] is able to suppress fast-growing human BON carcinoid tumors in nude mice. Furthermore, CgA is highly expressed in microdissected cells from carcinoid metastases, whereas it is not expressed in normal hepatocytes. Conclusion: Ad[CgA-E1A] is an interesting agent for the treatment of carcinoid liver metastases in conjunction with standard therapy for these malignancies.
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| 31. |
- Leja, Justyna, et al.
(författare)
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Double-detargeted oncolytic adenovirus shows replication arrest in liver cells and retains neuroendocrine cell killing ability
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:1, s. e8916-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:We have previously developed an oncolytic serotype 5 adenovirus (Ad5) with chromogranin-A (CgA) promoter-controlled E1A expression, Ad[CgA-E1A], with the intention to treat neuroendocrine tumors, including carcinoids. Since carcinoids tend to metastasize to the liver it is important to fully repress viral replication in hepatocytes to avoid adenovirus-related liver toxicity. Herein, we explore miRNA-based regulation of E1A expression as a complementary mechanism to promoter-based transcriptional control.METHODOLOGY/PRINCIPAL FINDINGS: Ad[CgA-E1A-miR122], where E1A expression is further controlled by six tandem repeats of the target sequence for the liver-specific miR122, was constructed and compared to Ad[CgA-E1A]. We observed E1A suppression and replication arrest of the miR122-detargeted adenovirus in normal hepatocytes, while the two viruses killed carcinoid cells to the same degree. Repeated intravenous injections of Ad[CgA-E1A] induced liver toxicity in mice while Ad[CgA-E1A-miR122] injections did not. Furthermore, a miR122-detargeted adenovirus with the wild-type E1A promoter showed reduced replication in hepatic cells compared to wild-type Ad5 but not to the same extent as the miR122-detargeted adenovirus with the neuroendocrine-selective CgA promoter.CONCLUSIONS/SIGNIFICANCE:A combination of transcriptional (promoter) and post-transcriptional (miRNA target) regulation to control virus replication may allow for the use of higher doses of adenovirus for efficient tumors treatment without liver toxicity.
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| 32. |
- Londos, Elisabet, et al.
(författare)
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Blood pressure and drug treatment in clinically diagnosed Lewy body dementia and Alzheimer's disease
- 2000
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Ingår i: Archives of Gerontology and Geriatrics. - 1872-6976. ; 30:1, s. 35-35
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to investigate arterial blood pressure (BP) and the use of pharmacological treatment in patients with Lewy body dementia (cLBD) and Alzheimer's disease (cAD) diagnosed on clinical grounds. BP and pharmacological treatment was analysed based on the medical records of 200 deceased dementia patients. Forty-eight cases with LBD and 45 AD were diagnosed using clinical criteria. The patients, who died between 1985 and 1994, were part of a prospective longitudinal dementia project. The majority of the cases were examined and cared for at the psychogeriatric and psychiatric departments. BP levels were very similar at an early stage of dementia but there was a marked decrease during the course of dementia in cAD and cLBD. The cLBD cases became hypotensive during the course of dementia to a significantly greater extent and also had a more pronounced drop in systolic BP at orthostatic testing compared to the cAD cases. cLBD and cAD were prescribed neuroleptics and medication potentially associated with hypotension to the same extent. The total number of these drugs was however higher in cLBD than in cAD. Antiparkinsonian treatment was, as expected, more common in cLBD compared to cAD. The findings suggest that insufficient BP regulation and drug treatment could affect the clinical picture of dementia, particularly in cLBD patients.
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| 33. |
- Londos, Elisabet, et al.
(författare)
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Clinical Lewy body dementia and the impact of vascular components
- 2000
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Ingår i: International Journal of Geriatric Psychiatry. - 1099-1166. ; 15:1, s. 40-49
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the prevalence of patients fulfilling the clinical consensus criteria for dementia with Lewy bodies (DLB) in a dementia population followed up with postmortem examination. To compare the clinical and neuropathological findings in the clinical Lewy body dementia (LBD) group with findings in a clinically defined group with Alzheimer's disease (AD). DESIGN: Medical records from 200 patients were studied retrospectively. Clinical consensus criteria for DLB and clinical criteria for other dementias were applied. SETTING: The majority of the cases were examined and cared for in psychogeriatric and psychiatric departments. PATIENTS: The patients, who died between 1985 and 1994, were part of a longitudinal dementia project. Each case was neuropathologically examined. Main outcome measures Prevalence of clinical signs and neuropathology was compared between the clinical groups. RESULTS: Forty-eight (24%) patients fulfilled the clinical criteria for DLB while 45 (22%) fulfilled the clinical criteria for Alzheimer's disease. The clinical LBD group had a higher Hachinski score compared to the clinical AD group. They also showed a tendency towards a 'frontal profile' with disinhibition, confusion, personality change and vocally disruptive behaviour. More than 80% of the AD and LBD groups respectively exhibited Alzheimer pathology. The LBD group had frontal white matter pathology and degeneration of the substantia nigra more often than the clinical AD group. Both LBD and AD groups showed a progressive and marked increase in severity of dementia and decrease in ADL capacity according to an evaluation based on the Berger scale and Katz index. The condition of the LBD group was significantly worse earlier in dementia. CONCLUSION: The results of this study indicate that patients fulfilling the clinical criteria for DLB also exhibit clinical features of possible vascular origin and a frontal profile. Subcortical vascular pathology, nigral degeneration and AD pathology in this group could partly explain the clinical features used to define DLB.
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| 34. |
- Londos, Elisabet, et al.
(författare)
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Contributions of other brain pathologies in dementia with lewy bodies.
- 2002
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 13:3, s. 130-148
-
Tidskriftsartikel (refereegranskat)abstract
- The clinical picture with its pathological correlate was analysed in 16 patients fulfilling consensus criteria for dementia with Lewy bodies (DLB). The cases were part of a larger cohort (n = 200) of patients within a prospective longitudinal study of dementing disorders. Six cases exhibited not only Lewy bodies (LBs) but also other brain pathologies such as Alzheimer changes, multiple infarcts or complete and incomplete white matter infarcts. Degeneration of the nucleus basalis of Meynert and substantia nigra was also seen. The 10 cases without LBs all had Alzheimer changes. In 7 cases, these changes were combined with mainly incomplete frontal white matter infarcts. However, the degeneration of brain stem nuclei was less pronounced in these cases. Symptoms such as fluctuations in cognition, falls and episodic confusion appeared in association with arterial hypotension, which developed during the course of dementia in almost all the 16 cases. The majority of the cases were treated with neuroleptics and other potentially hypotensive medication. This study shows that multiple and different pathological features may contribute to a clinical symptom constellation as in DLB. The case study approach reveals the complexity of the clinico-pathological relationships in dementia that might otherwise be lost in the analysis of larger group data. Copyright 2002 S. Karger AG, Basel
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| 35. |
- Londos, Elisabet, et al.
(författare)
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Neuropathological correlates to clinically defined dementia with Lewy bodies
- 2001
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Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 16:7, s. 667-679
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To analyse the neuropathological changes behind clinically defined dementia with Lewy bodies (clinDLB) compared with clinically diagnosed Alzheimer's disease (clinAD). METHODS: The prevalence of neuropathological findings in 48 clinDLB and 45 clinAD cases was compared. Sixteen clinDLB and 10 clinAD cases were reassessed with alpha-synuclein staining for Lewy bodies (LB). RESULTS: Alzheimer pathology was found in 81% of the clinDLB and 93% of the clinAD cases. The clinDLB group had a higher prevalence of frontal white matter pathology, mostly of ischemic type, and a more severe degeneration of the substantia nigra compared with the clinAD group. In hematoxylin-eosin staining, LBs were identified in seven (15%) of the clinDLB and in four (9%) of the clinAD group. In alpha-synuclein staining, 38% of the clinDLB and 40% of the clinAD cases exhibited LBs. The cases without LBs, in the clinDLB group, had AD pathology in combination with frontal white matter disease. Vascular pathology of significant degree was prevalent in more than 40% of all the cases with verified LBs regardless of clinical diagnosis. CONCLUSION: Consecutive dementia cases, fulfilling the clinical consensus criteria for DLB, may exhibit combinations of neuropathological changes which in themselves can explain the clinical picture of DLB even when LBs are absent.
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| 36. |
- Londos, Elisabet, et al.
(författare)
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Regional cerebral blood flow and EEG in clinically diagnosed dementia with Lewy bodies and Alzheimer's disease.
- 2003
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Ingår i: Archives of Gerontology and Geriatrics. - 1872-6976. ; 36:3, s. 231-245
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Tidskriftsartikel (refereegranskat)abstract
- This study was undertaken in order to compare regional cerebral blood now (rCBF) and EEG findings of patients with clinically diagnosed dementia with Lewy bodies (clinDLB) and Alzheimer’s disease (clinAD). Furthermore, within the clinDLB group to compare cases with and without neuropathologically verified Lewy bodies (LBs). When we studied 200 dementia cases in a prospective longitudinal dementia study, 48 had clinDLB and 45 clinAD in retrospective analyses. EEG information was analysed in 34 clinDLB and 28 clinAD patients and cerebral blood flow, measured with the Xe 133 inhalation method, in 26 clinDLB and 25 clinAD. There were no differences in EEG between the clinDLB and clinAD groups or between the cases with and without LBs. The rCBF patterns in the clinDLB and clinAD groups showed similar reductions in the temporoparietal areas. The rCBF in cases with LBs showed heterogeneous pathology. The imaging results in clinDLB and clinAD were strikingly similar. The EEG and rCBF could not differentiate between cases with or without LB. The study illustrates the lack of specific changes of EEG and rCBF in cases with LB pathology.
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| 37. |
- Naji, Hussein, 1971-, et al.
(författare)
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Vet doktorn hur en barnrumpa ser ut? : Sent upptäckta anorektala missbildningar hos barn
- 2011
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 108:46, s. 2380-2381
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Tidskriftsartikel (refereegranskat)abstract
- Av de 28 senaste barnen med anorektala missbildningar på vår klinik hade tolv fistel till perineum, analmembran eller fistel till vestibulum vaginae. Av dem upptäcktes fem sent – upp till sju månader efter födelsen.Tre av dessa fem hade uttalade förstoppningsbesvär med krystbeteende, och föräldrarna hade påpekat att anus hade avvikande utseende.Hos två av barnen visade utredning missbildningar i fler organ.
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| 38. |
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| 39. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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Dangerous liaisons : complement, coagulation, and kallikrein/kinin cross-talk act as a linchpin in the events leading to thromboinflammation
- 2016
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Ingår i: Immunological Reviews. - : Wiley. - 0105-2896 .- 1600-065X. ; 274:1, s. 245-269
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Forskningsöversikt (refereegranskat)abstract
- Innate immunity is fundamental to our defense against microorganisms. Physiologically, the intravascular innate immune system acts as a purging system that identifies and removes foreign substances leading to thromboinflammatory responses, tissue remodeling, and repair. It is also a key contributor to the adverse effects observed in many diseases and therapies involving biomaterials and therapeutic cells/organs. The intravascular innate immune system consists of the cascade systems of the blood (the complement, contact, coagulation, and fibrinolytic systems), the blood cells (polymorphonuclear cells, monocytes, platelets), and the endothelial cell lining of the vessels. Activation of the intravascular innate immune system in vivo leads to thromboinflammation that can be activated by several of the system's pathways and that initiates repair after tissue damage and leads to adverse reactions in several disorders and treatment modalities. In this review, we summarize the current knowledge in the field and discuss the obstacles that exist in order to study the cross-talk between the components of the intravascular innate immune system. These include the use of purified in vitro systems, animal models and various types of anticoagulants. In order to avoid some of these obstacles we have developed specialized human whole blood models that allow investigation of the cross-talk between the various cascade systems and the blood cells. We in particular stress that platelets are involved in these interactions and that the lectin pathway of the complement system is an emerging part of innate immunity that interacts with the contact/coagulation system. Understanding the resulting thromboinflammation will allow development of new therapeutic modalities.
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| 40. |
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| 41. |
- Passant, Ulla, et al.
(författare)
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Psychiatric Symptoms and Their Psychosocial Consequences in Frontotemporal Dementia.
- 2005
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Ingår i: Alzheimer Disease and Associated Disorders. - 0893-0341. ; 19 Suppl 1, s. 15-18
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Tidskriftsartikel (refereegranskat)abstract
- Based on a retrospective study of 19 neuropathologically verified cases with frontotemporal dementia (FTD), neuropsychiatric symptoms related to behavioral disturbances and their psychosocial consequences were studied. The results indicate that frontotemporal dementia is often misdiagnosed early in the clinical course. Behavioural features with impaired social interactions, impaired personal regulation, and loss of insight were seen in all patients. The psychosocial consequences reported in this paper challenge future research in frontotemporal dementia.
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| 42. |
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| 43. |
- Risberg, Jarl, et al.
(författare)
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Posterior cingulate cortex in familiar Alzheimer’s disease: A clinicopathological and brain imaging study
- 2003
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Ingår i: Journal of the International Neuropsychological Society. - 1355-6177. ; 9, s. 174-174
-
Konferensbidrag (refereegranskat)abstract
- The degenerative process in Alzheimer´s disease (AD) follows a temporal and topographic pattern of early and accentuated involvement of temporal limbic, parietal and posterior cingulate cortices. We have studied a pedigree with four generations suffering from early onset AD linked to a presenilin-1 gene mutation. This family now contains 7 AD cases, neuropathologically confirmed in four cases of three generations. In all four cases the degeneration was most pronounced in the temporoparietal cortex, but also engaged central grey structures such as the claustrum, central thalamic and brain stem nuclei. There was a consistent and severe degeneration in posterior cingulate cortex in contrast to a compara¬tively spared anterior cingulum. Regional cerebral blood flow (rCBF) was studied repeated¬ly with 133-xenon inhalation and SPECT methods. The rCBF measurements showed the typical cortical pathology of AD with bilateral decreases in temporoparietal and posterior cingulate cortices, accentuating over time and spreading anteriorly. There was a very good correspondence between clinical, neuroimaging and neuropathological features. Our findings indicate that posterior cingulum is a major locus for functional and structural vulnerability in both familial and sporadic forms of AD, something that might be used for diagnostic purposes together with possible posterior cingulate symptomatology.
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| 44. |
- Rosvall, Felicia, et al.
(författare)
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Clinical and Socioeconomic Effects of Misdiagnosed Wrist Ligament Injuries
- 2024
-
Ingår i: JOURNAL OF WRIST SURGERY. - 2163-3916 .- 2163-3924.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Misdiagnosed and maltreated wrist ligament injuries (scapholunate [SL], lunotriquetral, and triangular fibrocartilage complex [TFCC]) filed to the Swedish National Patient Insurance Company (LoF ["regionernas omsesidiga forsakringsbolag"]) 2011 to 2018 were analyzed in terms of complications and costs for society.Methods All filed claims are database registered. The database was assessed in June 2019 through injury International Classification of Diseases 10th Revision-SWE diagnoses. Demographics, reasons for avoidance, type of complication, and costs were assessed. Trend analysis was also used to compare the numbers of filed claims of wrist ligament injuries and total injuries.Results The mean age of the 231 extracted patients was 38 years. Females represented 57%. Ninety-eight (42%) of the claims were judged as avoidable, in accordance with the 40% approved patient injuries of all notified injuries during the same time period. Isolated injuries to the TFCC and SL ligament were the most common (n = 185, 80%). One to seven secondary surgical procedures/patient were needed to treat the condition. Sixty-nine (30%) of the 231 patients had medical invalidity due to the avoidable complication(s). Disability was more severe if more than one surgical procedure was needed. There was a significant trend toward decreasing numbers of filed claims for wrist ligament injuries ( p = 0.002) over time, in contrast to the total number of filed claims to LoF, which has increased by an average of 6% annually for a cumulative increase of 60% from 2011 to 2018.Interpretation The total cost for misdiagnosed and mistreated wrist ligament injuries in Sweden from 2011 to 2018 was euro2,203,467, and costly for both the patients and society at large.Level of Evidence Level III, therapeutic.
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| 45. |
- Stener-Victorin, Elisabet, 1964, et al.
(författare)
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Acupuncture and physical exercise for affective symptoms and health-related quality of life in polycystic ovary syndrome: Secondary analysis from a randomized controlled trial.
- 2013
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Ingår i: BMC complementary and alternative medicine. - : Springer Science and Business Media LLC. - 1472-6882. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Women with polycystic ovary syndrome (PCOS) have symptoms of depression and anxiety and impaired health related quality of life (HRQoL). Here we test the post-hoc hypothesis that acupuncture and exercise improve depression and anxiety symptoms and HRQoL in PCOS women. METHODS: Seventy-two PCOS women were randomly assigned to 16 weeks of 1) acupuncture (n = 28); 2) exercise (n = 29); or 3) no intervention (control) (n = 15). Outcome measures included: change in Montgomery Asberg Depression Rating Scale (MADRS-S), Brief Scale for Anxiety (BSA-S), Swedish Short-Form 36 (SF-36), and PCOS Questionnaire (PCOSQ) scores from baseline to after 16-week intervention, and to 16-week post-intervention follow-up. RESULTS: A reduction in MADRS-S and BSA-S from baseline to 16-weeks post-intervention follow-up was observed for the acupuncture group. The SF-36 domains role physical, energy/vitality, general health perception and the mental component of summary scores improved in the acupuncture group after intervention and at follow-up. Within the exercise group the role physical decreased after treatment, while physical functioning and general health perception scores increased at follow-up. The emotion domain in the PCOSQ improved after 16-weeks of intervention within all three groups, and at follow-up in acupuncture and exercise groups. At follow-up, improvement in the infertility domain was observed within the exercise group. CONCLUSION: There was a modest improvement in depression and anxiety scores in women treated with acupuncture, and improved HRQoL scores were noted in both intervention groups. While not a primary focus of the trial, these data suggest continued investigation of mental health outcomes in women treated for PCOS.Trial registration numberClinicalTrials.gov Identifier: NCT00484705.
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| 46. |
- Teramura, Yuji, et al.
(författare)
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A cell glue : Inducing cell adhesion using surface modification with cell-penetrating peptide-peg-lipid for 3d cell structures
- 2019
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Ingår i: The Pinnacle of Biomaterials Innovationand Excellence. - : Society for Biomaterials. - 9781510883901 ; , s. 678-
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Konferensbidrag (refereegranskat)abstract
- Statement of Purpose: The ultimate goal of regenerative therapy is the transplantation of functional stem cells-derived tissues and organs to replace those lost as the result of pathology or tissue damage. Since tissues and organs are complicated 3D structures, 3D scaffolds such as decellularized organs and tissues, are required to properly orient living functional cells of different types. 3D scaffolds offer an environment for cell adhesion that differs from that of conventional 2D culture. Therefore, the induction and control of cell attachment, not only to 2D substrate surfaces but also to 3D scaffolds, is of great importance. Here, we propose new type of cell glue made of cell-penetrating peptides (CPP) and PEG-conjugated lipid, which are used for cell-surface modification. PEG-lipid derivatives are incorporated into the lipid bilayer membranes of cells via hydrophobic interactions, and the CPP anchored onto the cell membrane could work as an adhesive domain. In our study, various floating cells, (i.e., T cells, B cells) were used to examine the adhesive efficacy by cell surface modification with CPP-PEG-lipid onto material surface as well as PS microfiber-based 3D scaffolds.
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| 47. |
- Teramura, Yuji, et al.
(författare)
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Cell Adhesion Induced Using Surface Modification with Cell-Penetrating Peptide-Conjugated Poly(ethylene glycol)-Lipid : A New Cell Glue for 3D Cell-Based Structures
- 2017
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 9:1, s. 244-254
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Tidskriftsartikel (refereegranskat)abstract
- We synthesized a novel material, cell-penetrating peptide conjugated poly(ethylene glycol)-lipid (CPP-PEG-lipid), that can induce the adhesion of floating cells. Firm cell adhesion with spreading could be induced by cell surface modification with the CPP-PEG-lipids. Cell adhesion was induced by CPPs but not by any other cationic short peptides we tested. Here, we demonstrated adherence using the floating cell line CCRF-CEM as well as primary human T cells, B cells, erythrocytes, and hepatocytes. As compared to cells grown in suspension, adherent cells were more rapidly induced to attach to substrates with the cell-surface modification. The critical factor for attachment was localization of CPPs at the cell membrane by PEG-lipids with PEG > 20 kDa. These cationic CPPs on PEG chains were able to interact with substrate surfaces such as polystyrene (PS) surfaces, glass surfaces, and PS microfibers that are negatively charged, inducing firm cell adhesion and cell spreading. Also, as opposed to normal cationic peptides that interact strongly with cell membranes, CPPs were less interactive with the cell surfaces because of their cell-penetrating property, making them more available for adhering cells to the substrate surface. No effects on cell viability or cell proliferation were observed after the induction of cell adhesion. With this technique, cells could be easily immobilized onto PS microfibers, an important step in fabricating 3D cell-based structures. Cells immobilized onto 3D PS microfibers were alive, and human hepatocytes showed normal production of urea and albumin on the microfibers. This method is novel in inducing firm cell adhesion-via a one-step treatment.
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- Ygland, Emil, et al.
(författare)
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Slowly progressive dementia caused by MAPT R406W mutations : longitudinal report on a new kindred and systematic review
- 2018
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Ingår i: Alzheimer's Research & Therapy. - : BioMed Central. - 1758-9193. ; 10
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Forskningsöversikt (refereegranskat)abstract
- Background: The MAPT c.1216C > T (p.Arg406Trp; R406W) mutation is a known cause of frontotemporal dementia with Parkinsonism linked to chromosome 17 tau with Alzheimer's disease-like clinical features. Methods: We compiled clinical data from a new Swedish kindred with R406W mutation. Seven family members were followed longitudinally for up to 22 years. Radiological examinations were performed in six family members and neuropathological examinations in three. We systematically reviewed the literature and compiled clinical, radiological, and neuropathological data on 63 previously described R406W heterozygotes and 3 homozygotes. Results: For all cases combined, the median age of onset was 56 years and the median disease duration was 13 years. Memory impairment was the most frequent symptom, behavioral disturbance and language impairment were less common, and Parkinsonism was rare. Disease progression was most often slow. The most frequent clinical diagnosis was Alzheimer's disease. R406W homozygotes had an earlier age at onset and a higher frequency of behavioral symptoms and Parkinsonism than heterozygotes. In the new Swedish kindred, a consistent imaging finding was ventromedial temporal lobe atrophy, which was evident also in early disease stages as a widening of the collateral sulcus with ensuing atrophy of the parahippocampal gyrus. Unlike previously published R406W carriers, all three autopsied patients from the novel family showed neuropathological similarities with progressive supranuclear palsy, with predominant four-repeat (exon 10+) tau isoform (4R) tauopathy and neurofibrillary tangles accentuated in the basal-medial temporal lobe. Amyloid-beta pathology was absent. Conclusions: Dominance of 4R over three-repeat (exon 10-) tau isoforms contrasts with earlier reports of R406W patients and was not sufficiently explained by the presence of H1/H2 haplotypes in two of the autopsied patients. R406W patients often show a long course of disease with marked memory deficits. Both our neuropathological results and our imaging findings revealed that the ventromedial temporal lobes were extensively affected in the disease. We suggest that this area may represent the point of origin of tau deposition in this disease with relatively isolated tauopathy.
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