| 61. |
- Herlin, Maria, et al.
(författare)
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Quantitative characterization of changes in bone geometry, mineral density and biomechanical properties in two rat strains with different Ah-receptor structures after long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin
- 2010
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Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 273:1-3, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Both industrial chemicals and environmental pollutants can interfere with bone modeling and remodeling. Recently, detailed toxicological bone studies have been performed following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which exerts most of its toxic effects through the aryl hydrocarbon receptor (AhR). OBJECTIVES: The aims of the present study were to quantitatively evaluate changes in bone geometry, mineral density and biomechanical properties following long-term exposure to TCDD, and to further investigate the role of AhR in TCDD-induced bone alterations. To this end, tissue material used in the study was derived from TCDD-exposed Long-Evans (L-E) and Han/Wistar (H/W) rats, which differ markedly in sensitivity to TCDD-induced toxicity due to a strain difference in AhR structure. METHODS: Ten weeks old female L-E and H/W rats were administered TCDD s.c. once per week for 20 weeks, at doses corresponding to calculated daily doses of 0, 1, 10, 100 and 1000ngTCDD/kgbw (H/W only). Femur, tibia and vertebra from the L-E and H/W rats were analyzed by peripheral quantitative computed tomography (pQCT) and biomechanical testing at multiple sites. Dose-response modeling was performed to establish benchmark doses for the analyzed bone parameters, and to quantify strain sensitivity differences for those parameters, which were affected by TCDD exposure in both rat strains. RESULTS: Bone geometry and bone biomechanical parameters were affected by TCDD exposure, while bone mineral density parameters were less affected. The trabecular area at proximal tibia and the endocortical circumference at tibial diaphysis were the parameters that showed the highest maximal responses. Significant strain differences in response to TCDD treatment were observed, with the L-E rat being the most sensitive strain. For the parameters that were affected in both strains, the differences in sensitivity were quantified, showing the most pronounced (about 49-fold) strain difference for cross-sectional area of proximal tibia. CONCLUSION: The study provides novel information about TCDD-induced bone alterations at doses, which are of relevance from a health risk assessment point of view. In addition, the obtained results provide further support for a distinct role of the AhR in TCDD-induced bone alterations, and suggest that the benchmark dose modeling approach is appropriate for quantitative evaluation of bone toxicity parameters.
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| 62. |
- Hermsen, Sanne A. B., et al.
(författare)
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In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects bone tissue in rhesus monkeys
- 2008
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Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 253:1-3, s. 147-152
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Tidskriftsartikel (refereegranskat)abstract
- Bone tissue is one of the target tissues for dioxins and dioxin-like compounds. Therefore, the aim of this study was to investigate effects of in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), oil bone tissue in rhesus monkey, the most human-like experimental model available, Pregnant rhesus monkeys (Macaca mulatta; age 4-10 years) were exposed to TCDD with a total dose of 40.5-42.0 or 405-420 ng/kg bodyweight by repeated subcutaneous injections starting at gestational day 20 and followed by injections every 30 days until 90 clays after delivery. At a mean age of 7 years the offspring were sacrificed and the femur bone dissected. Results from peripheral Quantitative Computed Tomography (pQCT) analyses of the metaphyseal part of the femur bones in female offspring showed significant increases in trabecular bone mineral content (BMC; +84.6%, p < 0.05, F-value (F)=5.9) in the low-dose treatment group compared with the controls. In the same animals, analysis of the mid-diaphyseal part revealed increases in total BMC (+21.3%. p < 0.05, F = 5.2) and cortical cross-sectional area (CSA; +16.4%. p < 0.01, F=7.4) compared with the controls. In males, changes in biomechanical properties indicating more fragile bone were observed. Displacement at failure were significantly increased in the male low-dose group compared to the controls (+38.0%, p, < 0.05, F=11). The high dose of TCDD did not induce any significant changes in bone morphology.
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| 63. |
- Hernefalk, Björn, et al.
(författare)
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Estimating pre-traumatic quality of life in patients with surgically treated acetabular fractures and pelvic ring injuries : Does timing matter?
- 2016
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Ingår i: Injury. - : Elsevier. - 0020-1383 .- 1879-0267. ; 47:2, s. 389-394
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Evaluation of patient-assessed functional outcome in traumatic conditions has specific challenges. To obtain pre-traumatic data to allow for comparison during follow-up, retrospective assessments are needed. How such data is affected by posttraumatic time-point chosen for evaluation is unknown. The primary purpose of this study was to investigate how the time-point chosen for retrospective assessment of pre-traumatic quality of life (QoL) in patients with surgically treated acetabular fractures and pelvic ring injuries influenced the results. A secondary purpose was to examine the pre-traumatic QoL-profile in patients with these injuries.PATIENTS AND METHODS: 73 patients were included, where 50 had an acetabular fracture and 23 a pelvic ring injury. Pre-traumatic QoL was evaluated using the generic instruments SF-36 and EQ5D in conjunction with the condition-specific Pelvic Trauma Questionnaire (PTQ). Questionnaires were completed at three time points: 0, 1 and 2 months post-surgery.RESULTS: Number of responders were 73 patients at 0 months, 61 patients at 1 month and 53 patients at 2 months. 50 patients answered the questionnaires at all three time-points. A trend was observed with all instruments where patients estimated a better pre-traumatic status with narrower distributions when assessment was delayed. At 2 months, scores for 4 out of 8 SF-36 domains where significantly higher compared to 0 months. For EQ5D, EQ VAS improved at 1 and 2 months compared to month 0 results but no other significant differences between time-points were found. Results from the PTQ demonstrated no significant differences over time. Pre-traumatic quality of life was high and for SF-36 comparable to a population norm. A very low level of pre-existing discomfort from the pelvic region was reported through the PTQ.CONCLUSION: Patients with surgically treated acetabular fractures and pelvic ring injuries estimate a higher pre-traumatic functional status when assessment is carried out at 1 or 2 months post-surgery compared to perioperative measurements. The SF-36 seems to be more sensitive than the EQ5D in this respect. Pre-traumatic QoL in patients with surgically treated acetabular fractures and pelvic ring injuries is generally high and pre-existing discomfort from the pelvic region is uncommon.
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| 64. |
- Hernefalk, Björn, et al.
(författare)
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Patient-reported Outcome in Surgically Treated Pelvic Ring Injuries at 5 Years Post-surgery
- 2021
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Ingår i: Scandinavian Journal of Surgery. - : Sage Publications. - 1457-4969 .- 1799-7267. ; 110:1, s. 86-92
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Long-term prospective data on patient-reported outcome after surgical treatment of pelvic ring injuries are scarce. This study aimed at describing results at 5 years post-surgery using validated outcome measures.PATIENTS AND METHODS: Patients admitted for surgical treatment of pelvic ring injuries were prospectively included and asked to report their outcome at 1, 2 and 5 years post-surgery using two patient-reported outcome measures: the generic Short-Form 36 and the condition-specific pelvic discomfort index. Data were evaluated using mixed-effects linear models.RESULTS: There were 108 patients (68 males and 40 females), mean age 38 years. Injury type according to the AO/OTA-classification was B-type in 68 patients and C-type in 40 patients. No domain of the Short-Form 36 reached norm values at 5 years post-surgery. Females reported a worse outcome than males concerning general health (p < 0.01) at 5 years. Recovery of physical function (p < 0.01), mental health (p = 0.04), and pain (p = 0.01) was observed for males at 5 years compared to earlier assessments, while females on the contrary described more pain at this time-point (p = 0.03). Mean pelvic discomfort index at 5 years was 27, indicating moderate residual pelvic discomfort overall. Males reported less pelvic discomfort than females at 5 years (p = 0.02) and improved when compared to results at 2 years (p = 0.02), while females did not. Influence of age, fracture type, and presence of associated injuries on patient-reported outcome was limited.CONCLUSION: Surgically treated pelvic ring injuries are associated with long-standing negative effects on patient-reported outcome. Males report a better outcome than females at 5 years post-surgery.
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| 65. |
- Hernefalk, Björn
(författare)
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Surgical Treatment of Pelvic Ring Injuries and Acetabular Fractures : Aspects on Patient-reported Outcome
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of the present thesis was to study the patient perspective on outcome following surgical treatment of pelvic ring injuries and acetabular fractures. All studies were based on patients treated for such injuries at the Department of Orthopaedics, Uppsala University Hospital, Sweden.In Study I, a patient-reported outcome measure to provide condition-specific information regarding outcome after surgical treatment of pelvic ring injuries was developed. Seventy-three patients were asked to complete a questionnaire at three time points during follow-up. Evaluation of data resulted in the Pelvic Discomfort Index (PDI). This instrument is comprised of six questions regarding residual problems from the pelvic region with respect to pain, walking, hip motion, leg numbness, sexual life and the operation scar.The influence of the time-point post-surgery at which patients with surgically treated pelvic ring injuries or acetabular fractures estimate their pre-traumatic state was examined in study II. Seventy-three patients assessed their pre-traumatic status at three time-points post-surgery. It was found that pre-traumatic quality of life was high and comparable to a reference population. Pre-existing discomfort from the pelvic region was uncommon. A tendency for patients to estimate a better pre-traumatic status when assessments were delayed was observed.The objective of Study III was to compare outcome after surgical treatment of complex acetabular fractures in the elderly using either the combined hip procedure, consisting of open reduction and internal fixation (ORIF) in conjunction with an acute total hip arthroplasty, or ORIF alone with respect to mortality, need for secondary surgery and patient-reported outcome. Thirteen patients treated with the CHP were compared to 14 patients with similar fracture patterns treated with ORIF alone. The CHP conferred a markedly reduced need for secondary surgical procedures while no differences in perioperative mortality or patient-reported outcome could be demonstrated.Patient-reported outcome at five years following surgical treatment of pelvic ring injury was evaluated in study IV. The consequences of these injuries were found to be substantial and long-standing. Females reported a worse outcome than males, while influence of variables age, injury type and presence of associated injuries was limited.In Study V, patient experiences of life following treatment for pelvic ring injury was explored. Semi-structured interviews were conducted with ten patients at a median of 11 years after injury and analyzed using inductive content analysis. Patients described a heterogenous outcome, with residual impairment ranging from virtually none to severe disability. A need for adequate patient information and individual assessments of patients was noted.
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| 66. |
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| 67. |
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| 68. |
- Hulsart-Billstrom, Gry, 1982-, et al.
(författare)
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Guiding bone formation using semi‐onlay calcium phosphate implants in an ovine calvarial model
- 2022
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Ingår i: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 16:5, s. 435-447
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Tidskriftsartikel (refereegranskat)abstract
- The restoration of cranio-maxillofacial deformities often requires complex reconstructive surgery in a challenging anatomical region, with abnormal soft tissue structures and bony deficits. In this proof-of-concept, the possibility of vertical bone augmentation was explored by suspending hemispherically shaped titanium-reinforced porous calcium phosphate (CaP) implants (n = 12) over the frontal bone in a sheep model (n = 6). The animals were euthanized after week 13 and the specimens were subject to micro-computed tomography (μCT) and comprehensive histological analysis. Histology showed that the space between implant and the recipient bone was filled with a higher percentage of newly formed bone (NFB) versus soft tissue with a median of 53% and 47%, respectively. Similar results were obtained from the μ-CT analysis, with a median of 56% NFB and 44% soft tissue filling the void. Noteworthy, significantly higher bone-implant contact was found for the CaP (78%, range 14%–94%) versus the Titanium (29%, range 0%–75%) portion of the implant exposed to the surrounding bone. The histological analysis indicates that the CaP replacement by bone is driven by macrophages over time, emphasized by material-filled macrophages found in close vicinity to the CaP with only a small number of single osteoclasts found actively remodeling the NFB. This study shows that CaP based implants can be assembled with the help of additive manufacturing to guide vertical bone formation without decortification or administration of growth factors. Furthermore, it highlights the potential disadvantage of a seamless fit between the implant and the recipient's bone.
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| 69. |
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| 70. |
- Hulsart-Billström, Gry, et al.
(författare)
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A surprisingly poor correlation between in vitro and in vivo testing of biomaterials for bone regeneration : Results of a multicentre analysis
- 2016
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Ingår i: European Cells & Materials. - 1473-2262. ; 31, s. 312-322
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Tidskriftsartikel (refereegranskat)abstract
- New regenerative materials and approaches need to be assessed through reliable and comparable methods for rapid translation to the clinic. There is a considerable need for proven in vitro assays that are able to reduce the burden on animal testing, by allowing assessment of biomaterial utility predictive of the results currently obtained through in vivo studies. The purpose of this multicentre review was to investigate the correlation between existing in vitro results with in vivo outcomes observed for a range of biomaterials. Members from the European consortium BioDesign, comprising 8 universities in a European multicentre study, provided data from 36 in vivo studies and 47 in vitro assays testing 93 different biomaterials. The outcomes of the in vitro and in vivo experiments were scored according to commonly recognised measures of success relevant to each experiment. The correlation of in vitro with in vivo scores for each assay alone and in combination was assessed. A surprisingly poor correlation between in vitro and in vivo assessments of biomaterials was revealed indicating a clear need for further development of relevant in vitro assays. There was no significant overall correlation between in vitro and in vivo outcome. The mean in vitro scores revealed a trend of covariance to in vivo score with 58 %. The inadequacies of the current in vitro assessments highlighted here further stress the need for the development of novel approaches to in vitro biomaterial testing and validated pre-clinical pipelines.
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