| 11. |
- Bengtsson, Daniel, 1975-, et al.
(författare)
-
Long-Term Outcome and MGMT as a Predictive Marker in 24 Patients With Atypical Pituitary Adenomas and Pituitary Carcinomas Given Treatment With Temozolomide
- 2015
-
Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 100:4, s. 1689-1698
-
Tidskriftsartikel (refereegranskat)abstract
- Context/Objective: Locally aggressive pituitary tumors (LAPT) and pituitary carcinomas respond poorly to conventional therapy and cytotoxic drugs. Temozolomide (TMZ) is an oral alkylating drug with good tolerability, approved for treatment of malignant gliomas. The experience of its use in pituitary tumors is limited. Design and Setting: We report on 24 patients with aggressive pituitary tumors (16 LAPTs, 8 carcinomas) treated with TMZ for a median of 6 months (range 1-23). Follow-up ranged from 4 to 91 months with a median of 32.5 months. 19/24 tumors were hormone secreting (PRL 9, ACTH 4, GH 4, GH/PRL 2). Ki-67 was 2-50% in LAPTs, and 5-80% in carcinomas. Main Outcome: Response to TMZ and the association with tumor expression of O6-methylguanine DNA methyltransferase (MGMT), MLH1, MSH2, and MSH6, examined by immunohistochemistry. Results: Complete tumor regression occurred in two carcinomas and persisted at follow-up after 48 and 91 months, respectively. Partial regress of tumor mass ranging from 35% to 80% occurred in 5 LAPTs and 2 carcinomas. Another patient with LAPT had a 71% decrease in prolactin levels without change in tumor volume. Three LAPTs could not be evaluated. Median MGMT staining was 9% (5-20%) in responders vs 93% (50-100%) in nonresponders. Loss of MSH2 and MSH 6 was observed in a single patient who had a rapid development of resistance to TMZ. Conclusions: This study shows that TMZ is a valuable treatment option for patients with uncontrolled pituitary tumors. The data suggest that tumoral MGMT staining below 50% is associated with a high likelihood of treatment response.
|
|
| 12. |
- Broomé, Sofia, et al.
(författare)
-
Dynamics are important for the recognition of equine pain in video
- 2019
-
Ingår i: Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition. - : Institute of Electrical and Electronics Engineers (IEEE). - 1063-6919.
-
Konferensbidrag (refereegranskat)abstract
- A prerequisite to successfully alleviate pain in animals is to recognize it, which is a great challenge in non-verbal species. Furthermore, prey animals such as horses tend to hide their pain. In this study, we propose a deep recurrent two-stream architecture for the task of distinguishing pain from non-pain in videos of horses. Different models are evaluated on a unique dataset showing horses under controlled trials with moderate pain induction, which has been presented in earlier work. Sequential models are experimentally compared to single-frame models, showing the importance of the temporal dimension of the data, and are benchmarked against a veterinary expert classification of the data. We additionally perform baseline comparisons with generalized versions of state-of-the-art human pain recognition methods. While equine pain detection in machine learning is a novel field, our results surpass veterinary expert performance and outperform pain detection results reported for other larger non-human species.
|
|
| 13. |
- Chiotis, Konstantinos, et al.
(författare)
-
Imaging in-vivo tau pathology in Alzheimer's disease with THK5317 PET in a multimodal paradigm
- 2016
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 43:9, s. 1686-1699
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose The aim of this study was to explore the cerebral distribution of the tau-specific PET tracer [F-18]THK5317 (also known as (S)-[F-18]THK5117) retention in different stages of Alzheimer's disease; and study any associations with markers of hypometabolism and amyloid-beta deposition. Methods Thirty-three individuals were enrolled, including nine patients with Alzheimer's disease dementia, thirteen with mild cognitive impairment (MCI), two with non-Alzheimer's disease dementia, and nine healthy controls (five young and four elderly). In a multi-tracer PET design [F-18]THK5317, [C-11] Pittsburgh compound B ([C-11]PIB), and [F-18]FDG were used to assess tau pathology, amyloid-beta deposition and cerebral glucose metabolism, respectively. The MCI patients were further divided into MCI [C-11]PIB-positive (n=11) and MCI [C-11]PIB-negative (n=2) groups. Results Test-retest variability for [F-18]THK5317-PET was very low (1.17-3.81 %), as shown by retesting five patients. The patients with prodromal (MCI [C-11]PIB-positive) and dementia-stage Alzheimer's disease had significantly higher [F-18]THK5317 retention than healthy controls (p=0.002 and p=0.001, respectively) in areas exceeding limbic regions, and their discrimination from this control group (using the area under the curve) was >98 %. Focal negative correlations between [F-18]THK5317 retention and [F-18]FDG uptake were observed mainly in the frontal cortex, and focal positive correlations were found between [F-18]THK5317 and [C-11] PIB retentions isocortically. One patient with corticobasal degeneration syndrome and one with progressive supranuclear palsy showed no [C-11]PIB but high [F-18]THK5317 retentions with a different regional distribution from that in Alzheimer's disease patients. Conclusions The tau-specific PET tracer [F-18]THK5317 images in vivo the expected regional distribution of tau pathology. This distribution contrasts with the different patterns of hypometabolism and amyloid-beta deposition.
|
|
| 14. |
- Englund, Elias, et al.
(författare)
-
Metabolic Engineering of Synechocystis sp. PCC 6803 for Production of the Plant Diterpenoid Manoyl Oxide
- 2015
-
Ingår i: ACS Synthetic Biology. - : American Chemical Society (ACS). - 2161-5063. ; 4:12, s. 1270-1278
-
Tidskriftsartikel (refereegranskat)abstract
- Forskolin is a high value diterpenoid with a broad range of pharmaceutical applications, naturally found in root bark of the plant Coleus forskohlii. Because of its complex molecular structure, chemical synthesis of forskolin is not commercially attractive. Hence, the labor and resource intensive extraction and purification from C. forskohlii plants remains the current source of the compound. We have engineered the unicellular cyanobacterium Synechocystis sp. PCC 6803 to produce the forskolin precursor 13R-manoyl oxide (13R-MO), paving the way for light driven biotechnological production of this high value compound. In the course of this work, a new series of integrative vectors for use in Synechocystis was developed and used to create stable lines expressing chromosomally integrated CfTPS2 and CfTPS3, the enzymes responsible for the formation of 13R-MO in C. forskohlii. The engineered strains yielded production titers of up to 0.24 mg g(-1) DCW 13R-MO. To increase the yield, 13R-MO producing strains were further engineered by introduction of selected enzymes from C. forskohlii, improving the titer to 0.45 mg g(-1) DCW. This work forms a basis for further development of production of complex plant diterpenoids in cyanobacteria.
|
|
| 15. |
- Eriksen, Jaran, et al.
(författare)
-
High adherence to the 'Wise List' treatment recommendations in Stockholm : a 15-year retrospective review of a multifaceted approach promoting rational use of medicines
- 2017
-
Ingår i: BMJ Open. - London, UK : BMJ Publishing Group Ltd. - 2044-6055. ; 7:4
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To present the 'Wise List' (a formulary of essential medicines for primary and specialised care in Stockholm Healthcare Region) and assess adherence to the recommendations over a 15-year period.DESIGN: Retrospective analysis of all prescription data in the Stockholm Healthcare Region between 2000 and 2015 in relation to the Wise List recommendations during the same time period.SETTING: All outpatient care in the Stockholm Healthcare Region.PARTICIPANTS: All prescribers in the Stockholm Healthcare Region.MAIN OUTCOME MEASURES: The number of core and complementary substances included in the Wise List, the adherence to recommendations by Anatomic Therapeutic Chemical (ATC) 1st level using defined daily doses (DDDs) adjusted to the DDD for 2015, adherence to recommendations over time measured by dispensed prescriptions yearly between 2002 and 2015.RESULTS: The number of recommended core substances was stable (175-212). Overall adherence to the recommendations for core medicines for all prescribers increased from 75% to 84% (2000 to 2015). The adherence to recommendations in primary care for core medicines increased from 80% to 90% (2005 to 2015) with decreasing range in practice variation (32% to 13%). Hospital prescriber adherence to core medicine recommendations was stable but increased for the combination core and complementary medicines from 77% to 88% (2007 to 2015). Adherence varied between the 4 therapeutic areas studied.CONCLUSIONS: High and increasing adherence to the Wise List recommendations was seen for all prescriber categories. The transparent process for developing recommendations involving respected experts and clinicians using strict criteria for handling potential conflicts of interests, feedback to prescribers, continuous medical education and financial incentives are possible contributing factors. High-quality evidence-based recommendations to prescribers, such as the Wise List, disseminated through a multifaceted approach, will become increasingly important and should be developed further to include recommendations and introduction protocols for new expensive medicines.
|
|
| 16. |
- Farid, Karim, et al.
(författare)
-
Case Report of Complex Amyotrophic Lateral Sclerosis with Cognitive Impairment and Cortical Amyloid Deposition.
- 2015
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908 .- 1387-2877. ; 47:3, s. 661-7
-
Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS), a fatal disease of unknown origin, affects motor neurons in the primary motor cortex, brainstem, and spinal cord. Cognitive impairment may occur before the motor symptoms. We present a patient who was initially diagnosed with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) but who developed ALS-like symptoms during follow-up and died shortly thereafter. A 60-year-old subject with cognitive impairment underwent neuropsychological testing, cerebrospinal fluid (CSF) analysis, structural imaging (computed tomography and magnetic resonance imaging) and functional imaging [11C]-Pittsburgh compound B (PIB) positron emission tomography (PET), [18F]-fluorodeoxyglucose (FDG) PET, and [11C]-deuterium-L-deprenyl (DED) PET. Neuropsychological testing showed episodic memory impairment. CSF P-tau and T-tau levels were elevated. CSF amyloid-β (Aβ)42 levels were initially normal but became pathological during follow-up. MCI was diagnosed. [18F]-FDG PET showed hypometabolism in the left temporal and prefrontal cortices and [11C]-PIB PET demonstrated amyloid plaque deposition in the prefrontal, posterior cingulate, and parietal cortices. [11C]-DED PET showed high brain accumulation consistent with astrocytosis. The memory impairment progressed and AD was diagnosed. Motor impairments developed subsequently and, following additional neurological evaluation, ALS was diagnosed. The disease progressed rapidly and the patient died with pronounced motor symptoms three years after the initial cognitive assessment. Since relatives refused autopsy, postmortem analysis was not possible.
|
|
| 17. |
|
|
| 18. |
- Haubro Andersen, Pia
(författare)
-
Accuracy and precision of oscillometric blood pressure in standing conscious horses
- 2016
-
Ingår i: Journal of Veterinary Emergency and Critical Care. - : Wiley. - 1479-3261 .- 1476-4431. ; 26, s. 85-92
-
Tidskriftsartikel (refereegranskat)abstract
- Background - Arterial blood pressure (BP) is a relevant clinical parameter that can be measured in standing conscious horses to assess tissue perfusion or pain. However, there are no validated oscillometric noninvasive blood pressure (NIBP) devices for use in horses.Animals - Seven healthy horses from a teaching and research herd.Hypothesis/Objective - To evaluate the accuracy and precision of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) in conscious horses obtained with an oscillometric NIBP device when compared to invasively measured arterial BP.Methods - An arterial catheter was placed in the facial or transverse facial artery and connected to a pressure transducer. A cuff for NIBP was placed around the tail base. The BP was recorded during normotension, dobutamine-induced hypertension, and subnormal BP induced by acepromazine administration. Agreement analysis with replicate measures was utilized to calculate bias (accuracy) and standard deviation (SD) of bias (precision).Results - A total of 252 pairs of invasive arterial BP and NIBP measurements were analyzed. Compared to the direct BP measures, the NIBP MAP had an accuracy of -4 mm Hg and precision of 10 mm Hg. SAP had an accuracy of -8 mm Hg and a precision of 17 mm Hg and DAP had an accuracy of -7 mm Hg and a precision of 14 mm Hg.Conclusions and Clinical Relevance - MAP from the evaluated NIBP monitor is accurate and precise in the adult horse across a range of BP, with higher variability during subnormal BP. MAP but not SAP or DAP can be used for clinical decision making in the conscious horse.
|
|
| 19. |
- Haubro Andersen, Pia
(författare)
-
An equine pain face
- 2015
-
Ingår i: Veterinary Anaesthesia and Analgesia. - : Elsevier BV. - 1467-2987 .- 1467-2995. ; 42, s. 103-114
-
Tidskriftsartikel (refereegranskat)abstract
- Conclusions and clinical relevanceAn equine pain face comprising low' and/or asymmetrical' ears, an angled appearance of the eyes, a withdrawn and/or tense stare, mediolaterally dilated nostrils and tension of the lips, chin and certain facial muscles can be recognized in horses during induced acute pain. This description of an equine pain face may be useful for improving tools for pain recognition in horses with mild to moderate pain.
|
|
| 20. |
|
|
