| 1. |
- Evangelou, Evangelos, et al.
(författare)
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Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:2, s. 349-355
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p = 9.2 x 10(-9)), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
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| 2. |
- Wilson, Andrew D H, et al.
(författare)
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Acetyl-l-carnitine increases nerve regeneration and target organ reinnervation : A morphological study
- 2010
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Ingår i: Journal of Plastic, Reconstructive & Aesthetic Surgery. - : Elsevier. - 1748-6815 .- 1878-0539. ; 63:7, s. 1186-1195
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Tidskriftsartikel (refereegranskat)abstract
- Peripheral nerve injury frequently results in functional morbidity since standard management fails to adequately address many of the neurobiological hurdles to optimal regeneration. Neuronal survival and regeneration are neurotrophin dependent and require increased aerobic capacity. Acetyl-l-carnitine (ALCAR) facilitates this need and prevents neuronal loss. ALCAR is clinically safe and is shown here to significantly improve nerve regeneration and target organ reinnervation. Two groups of five rats underwent sciatic nerve division followed by immediate repair. One group received parenteral ALCAR (50mg/kg/day) from time of operation until termination at 12 weeks. A 'sham treatment' group received normal saline. A third group was left unoperated and did not receive any treatment. A segment of nerve was harvested between 5mm proximal and 10mm distal to the repair in operated groups, and at the corresponding level in the unoperated group. Mean axonal count in normal, non-axotomised nerve was 14,720 (SD 2378). That of the saline group (17,217 SD 1808) was not significantly different from normal nerve (P=0.0985). Mean number of myelinated axons in the ALCAR group (24,460 SD 3750) was significantly greater than both sham group (P<0.01) and normal nerve (P=0.0012). Mean myelin thickness in the saline treated group (0.408mum SD 0.067mum) was less than normal nerve (0.770mum SD 0.143mum) (P<0.001). Mean myelin thickness in the ALCAR group (0.627mum SD 0.052mum) was greater than the sham (saline) group (P<0.01) and not statistically different from normal nerve (P=0.07). ALCAR increased dermal PGP9.5 staining by 210% compared to sham treatment (P<0.0001) and significantly reduced the mean percentage weight loss in gastrocnemius muscle (ALCAR group 0.203% vs. 0.312% in sham group P=0.015). ALCAR not only increases the number of regenerating nerve fibres but also morphologically improves the quality of regeneration and target organ reinnervation. Adjuvant ALCAR treatment may improve both sensory and motor outcomes and merits further investigation.
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| 3. |
- Ackermann, Paul W, et al.
(författare)
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Neuronal pathways in tendon healing and tendinopathy : update
- 2014
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Ingår i: Frontiers in Bioscience-Landmark. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1093-4715 .- 1093-9946 .- 2768-6698.
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Tidskriftsartikel (refereegranskat)abstract
- The regulatory mechanisms involved in tendon homeostasis and repair are not fully understood. Accumulating data, however, demonstrate that the nervous system, in addition to afferent (sensory) functions, through efferent neuronal pathways plays an active role in regulating pain, inflammation, and tissue repair processes. Thus, in normal-, healing- and tendinopathic tendons three major neuronal signalling pathways consisting of autonomic, sensory and glutamatergic neuromediators have been established. In healthy tendons, these neural elements are found in the paratenon, whereas the proper tendon is practically devoid of nerves, reflecting that normal tendon homeostasis is regulated by pro- and anti-inflammatory mediators from the tendon surroundings. During tendon repair, however, there is extensive nerve ingrowth into the tendon proper and subsequent time-dependent appearance of sensory, autonomic and glutamatergic mediators, which amplify and fine-tune inflammation and tendon regeneration. In tendinopathy, excessive and protracted sensory and glutamatergic signalling may be involved in inflammatory, painful and hypertrophic tissue reactions. As our understanding of these processes improves, neuronal mediators may prove to be useful in the development of targeted pharmacotherapy and tissue engineering approaches to painful, degenerative and traumatic tendon disorders.
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| 4. |
- Booth, Malcolm G, et al.
(författare)
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Anthrax infection in drug users
- 2010
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 375:9723, s. 1345-1346
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Button, J., et al.
(författare)
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Shoulder function following autologous latissimus dorsi breast reconstruction : A prospective three year observational study comparing quilting and non-quilting donor site techniques
- 2010
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Ingår i: Journal of Plastic, Reconstructive & Aesthetic Surgery. - : Elsevier BV. - 1748-6815 .- 1878-0539. ; 63:9, s. 1505-1512
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Tidskriftsartikel (refereegranskat)abstract
- Latissimus dorsi harvest and axillary surgery can affect shoulder function. The effect of autologous latissimus dorsi flap (ALD) breast reconstruction and donor site quilting have been inadequately studied. A cohort of ALD flap breast reconstruction patients were assessed pre-operatively and at eight post-operative time-points (up to 3 years after reconstruction) using the self-administered Disabilities of the Arm, Shoulder and Hand (DASH) outcome measure, for which validated normative data is available. Patients with incidental shoulder conditions and bilateral reconstructions were excluded. This was a prospective, observational study with blinded data interpretation: 58 patients, 22 of whom had donor site quilting, were assessed. Groups were compatible demographically, in breast care management and in pre-operative DASH score (quilted 6.5, non-quilted 6.4; P = 0.98). Scores were significantly increased at initial post-operative clinic review (mean 49, SD19; P < 0.001), 6 week (29, SD20; P < 0.001), and 3 month (19, SD19; P < 0.01), thereafter remaining at a plateau value of similar to 15 (P > 0.05). Seroma incidence was reduced in the quilted group (5% vs 70%). A strong, significant correlation was found between 3 month DASH score and long term function (r = 0.66, P < 0.0003); patients with DASH > 20 fare significantly worse in the long-term (mean 20 point increase, SD5.0, P < 0.001). Higher post-operative DASH scores correlated significantly with pre-operative DASH (r = 0.58) and BMI (r = 0.36). Adjuvant therapy had no effect on shoulder function. Axillary dissection had a weak correlation with a higher DASH score, but only at the 3-month post-operative time-point (r = 0.32, P = 0.03). ALD flap breast reconstruction generally results in a functionally insignificant increase (6.5 points) in longterm DASH score, although a small subset of patients do develop longterm impairment, and quilting does not appear to inhibit shoulder function. (C) 2009 British Association of Plastic, Reconstructive and Aesthetic Surgeons.
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| 6. |
- Chan, Simon S. M., et al.
(författare)
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Body Mass Index and the Risk for Crohn's Disease and Ulcerative Colitis : Data From a European Prospective Cohort Study (The IBD in EPIC Study)
- 2013
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Ingår i: American Journal of Gastroenterology. - New York, NY, USA : Nature Publishing Group. - 0002-9270 .- 1572-0241. ; 108:4, s. 575-582
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Obesity is associated with a proinflammatory state that may be involved in the etiology of inflammatory bowel disease (IBD), for which there are plausible biological mechanisms. Our aim was to perform the first prospective cohort study investigating if there is an association between obesity and the development of incident IBD. METHODS: A total of 300,724 participants were recruited into the European Prospective Investigation into Cancer and Nutrition study. At recruitment, anthropometric measurements of height and weight plus physical activity and total energy intake from validated questionnaires were recorded. The cohort was monitored identifying participants who developed either Crohn's disease (CD) or ulcerative colitis (UC). Each case was matched with four controls and conditional logistic regression used to calculate odds ratios (ORs) for body mass index (BMI) adjusted for smoking, energy intake, and physical activity. RESULTS: In the cohort, 177 participants developed incident UC and 75 participants developed incident CD. There were no associations with the four higher categories of BMI compared with a normal BMI for UC (P-trend = 0.36) or CD (P-trend = 0.83). The lack of associations was consistent when BMI was analyzed as a continuous or binary variable (BMI 18.5 <25.0 vs. >= 25 kg/m(2)). Physical activity and total energy intake, factors that influence BMI, did not show any association with UC (physical activity, P-trend = 0.79; total energy intake, P-trend = 0.18) or CD (physical activity, P-trend = 0.42; total energy, P-trend = 0.11). CONCLUSIONS: Obesity as measured by BMI is not associated with the development of incident UC or CD. Alternative measures of obesity are required to further investigate the role of obesity in the development of incident IBD.
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| 7. |
- Chan, Simon S. M., et al.
(författare)
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Carbohydrate Intake in the Etiology of Crohn's Disease and Ulcerative Colitis
- 2014
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Ingår i: Inflammatory Bowel Diseases. - : Lippincott Williams & Wilkins. - 1078-0998 .- 1536-4844. ; 20:11, s. 2013-2021
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diet may have a role in the etiology of inflammatory bowel disease. In previous studies, the associations between increased intakes of carbohydrates, sugar, starch, and inflammatory bowel disease are inconsistent. However, few prospective studies have investigated the associations between these macronutrients and incident Crohn's disease (CD) or ulcerative colitis (UC). Methods: A total of 401,326 men and women were recruited between 1991 and 1998. At recruitment, dietary intakes of carbohydrate, sugar, and starch were measured using validated food frequency questionnaires. The cohort was monitored identifying participants who developed incident CD or UC. Cases were matched with 4 controls, and odds ratios were calculated for quintiles of total carbohydrate, sugar, and starch intakes adjusted for total energy intake, body mass index, and smoking. Results: One hundred ten participants developed CD, and 244 participants developed UC during follow-up. The adjusted odds ratio for the highest versus the lowest quintiles of total carbohydrate intake for CD was 0.87, 95% CI = 0.24 to 3.12 and for UC 1.46, 95% CI = 0.62 to 3.46, with no significant trends across quintiles for either (CD, P-trend = 0.70; UC, P-trend = 0.41). Similarly, no associations were observed with intakes of total sugar (CD, P-trend = 0.50; UC, P-trend = 0.71) or starch (CD, P-trend = 0.69; UC, P-trend = 0.17). Conclusions: The lack of associations with these nutrients is in agreement with many case-control studies that have not identified associations with CD or UC. As there is biological plausibility for how specific carbohydrates could have an etiological role in inflammatory bowel disease, future epidemiological work should assess individual carbohydrates, although there does not seem to be a macronutrient effect.
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| 8. |
- Chin, Kuen Yeow, et al.
(författare)
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Melanoma diagnosed 27 years after a benoxaprofen-induced photosensitivity reaction
- 2012
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Ingår i: Journal of Dermatological Case Reports. - : Specjalisci Dermatolodzy. - 1898-7249. ; 6:1, s. 5-7
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Tidskriftsartikel (refereegranskat)abstract
- Background: The propionic acid derivative Benoxaprofen was introduced for the treatment of rheumatic disorders in 1980. Its product license was then withdrawn2 years later due to concerns over serious dermatologic, hepatic and renal side effects. Photosensitivity was the most common side effect with reported incidence of up to 50%.Main observations: We present the first case report of a patient who presented with a melanoma diagnosed 27 years after a benoxaprofen-induced photosensitivity reaction. With an estimated 1.5 million patients previously on benoxaprofen, a large number of patients may potentially face increased risk of developing malignant melanoma. This case report can only suggest an association between solar injury secondary to benoxaprofen-related photosensitivity and subsequent melanoma. However the primary factor that improves survival from melanoma is early diagnosis, and so clinicians treating this group of patients should be aware of this risk.Conclusion: Although benoxaprofen is no longer in clinical use, the long-term sequelae to its photosensitizing effects may still be clinically important. Clinicians treating this group of patients should be vigilant, and consider a low threshold for diagnostic biopsy of suspicious skin lesions.
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| 9. |
- Cotrufo, Stefano, et al.
(författare)
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The Vascular Anatomy of the Rat Superficial Epigastric Flap by Vascular Corrosion Casting and Technical Refinement for the Study of Choke Vessels in Cadaveric Flap Models
- 2010
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Ingår i: Annals of Plastic Surgery. - : Lippincott Williams & Wilkins. - 0148-7043 .- 1536-3708. ; 64:1, s. 93-97
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Tidskriftsartikel (refereegranskat)abstract
- Accurate depiction of cutaneous vascular microanatomy is of relevance to plastic surgical flap research, and to descriptive anatomy. Yet current techniques have not permitted full visualization of the subdermal plexus, or potential angiosomal connections. Nor has endothelial visualization been facilitated. Vascular corrosion casting techniques are promising in that regard, and were applied in an extended lateral thoracoabdominal suprafascial adipocutancous flap in the rat (based on the superficial epigastric bundle). Technical refinements for application to further study of human cadaveric flap models are presented. The intraflap vascular branching pattern of the superficial epigastric artery is described, with filling of the lateral thoracic, intercostals, and iliolumbar angiosomes found when coagulation of vessels at the periphery was delayed until after clearance. The vascular casting protocol presented is an effective and promising tool for the study of macro- and microvascular anatomy.
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| 10. |
- Crotty Alexander, Laura E., et al.
(författare)
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Myeloid cell HIF-1 alpha regulates asthma airway resistance and eosinophil function
- 2013
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Ingår i: Journal of Molecular Medicine. - : Springer Verlag (Germany). - 0946-2716 .- 1432-1440. ; 91:5, s. 637-644
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Tidskriftsartikel (refereegranskat)abstract
- Hypoxia-inducible factor (HIF)-1 alpha is a master regulator of inflammatory activities of myeloid cells, including neutrophils and macrophages. These studies examine the role of myeloid cell HIF-1 alpha in regulating asthma induction and pathogenesis, and for the first time, evaluate the roles of HIF-1 alpha and HIF-2 alpha in the chemotactic properties of eosinophils, the myeloid cells most associated with asthma. Wild-type (WT) and myeloid cell-specific HIF-1 alpha knockout (KO) C57BL/6 mice were studied in an ovalbumin (OVA) model of asthma. Administration of the pharmacological HIF-1 alpha antagonist YC-1 was used to corroborate findings from the genetic model. WT, HIF-1 alpha, and HIF-2 alpha KO eosinophils underwent in vitro chemotaxis assays. We found that deletion of HIF-1 alpha in myeloid cells and systemic treatment with YC-1 during asthma induction decreased airway hyperresponsiveness (AHR). Deletion of HIF-1 alpha in myeloid cells in OVA-induced asthma also reduced eosinophil infiltration, goblet cell hyperplasia, and levels of cytokines IL-4, IL-5, and IL-13 in the lung. HIF-1 alpha inhibition with YC-1 during asthma induction decreased eosinophilia in bronchoalveolar lavage, lung parenchyma, and blood, as well as decreased total lung inflammation, IL-5, and serum OVA-specific IgE levels. Deletion of HIF-1 alpha in eosinophils decreased their chemotaxis, while deletion of the isoform HIF-2 alpha led to increased chemotaxis. This work demonstrates that HIF-1 alpha in myeloid cells plays a role in asthma pathogenesis, particularly in AHR development. Additionally, treatment with HIF-1 alpha inhibitors during asthma induction decreases AHR and eosinophilia. Finally, we show that HIF-1 alpha and HIF-2 alpha regulate eosinophil migration in opposing ways.
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| 11. |
- Dabernig, Jörg, et al.
(författare)
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The anatomic and radiologic basis of the circumflex scapular artery perforator flap
- 2010
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Ingår i: Annals of Plastic Surgery. - 0148-7043 .- 1536-3708. ; 64:6, s. 784-788
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Tidskriftsartikel (refereegranskat)abstract
- Microsurgical development has recently focused upon the perforator paradigm and primary thinning. Existing perforator flaps may require intramuscular dissection or lack reliable surface markings, whereas traditional scapular/parascapular flaps have low donor morbidity and reliable anatomy, but can be excessively bulky. Clinical application of a new flap based on a perforator from the circumflex scapular axis (CSA) has recently been published, but the vessel's anatomy has not been adequately characterized. The CSA was dissected in 115 sites in 69 cadavers. The number, external vessel diameter, and site of origin of perforators were measured relative to the CSA bifurcation. Color Doppler ultrasound was used to delineate the CSA and its perforators bilaterally in 40 volunteers. The number, origin relative to CSA bifurcation, diameter, length, and flow velocity of cutaneous perforators were determined. A CSA perforator was always present, running into the subdermal plexus, arising within 2.4 cm of the bifurcation. Cadaver studies: mean perforator diameter, 1.3 mm (SD, 0.66); 13% arose at bifurcation, 36% arose proximal (mean, 1.1 mm; SD, 0.63), and 52% distal to bifurcation (mean, 1.5 mm; SD, 0.88). Ultrasound: mean perforator diameter, 1.18 mm (SD, 0.41); mean flow velocity, 16.3 cm/s (SD, 3.65); perforator arose in 36% proximal, in 40% distal to bifurcation, and in 24% from the bifurcation. We definitively describe the anatomy of the perforator from the circumflex scapular artery upon which a new flap has been based. Its origin and dimensions are anatomically and radiologically reliable. The flap has certain potential benefits over existing perforator flaps.
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| 12. |
- Hart, Andrew, et al.
(författare)
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Tissue Engineering for Peripheral Nerve Regeneration
- 2011
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Ingår i: Tissue Engineering. - Berlin : Springer Berlin/Heidelberg. - 9783642028236 - 9783642028243 ; , s. 245-262
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The outcome of peripheral nerve repair has changed very little over the past 50 years, and clinical outcomes remain generally poor. Surgical technique has evolved to a high level of technical microsurgical proficiency, but this approach remains unable to adequately address the neurobiological barriers to the optimization of nerve regeneration. Reconstruction of complex segmental injuries, as in the brachial plexus, additionally requires a considerable length of interpositional nerve autograft, which may be unobtainable without considerable donor morbidity.Research has therefore turned to the modulation of the repair-site environment to optimise nerve regeneration across neurorraphies, and to the creation of nerve conduits to reduce the need for nerve autograft. Tissue engineering has involved the use of growth factors to modulate neuronal and glial cell behaviour, and the creation of macro, micro and nanoscale constructs from a variety of materials in order to replace the connective tissue functions of nerve autograft. Implantation of cultured Schwann and stem cells is an area of particular development given the necessity of viable support cells to facilitate neuronal growth. These approaches are reviewed in the light of current published work.The future of peripheral nerve repair lies in the modulation of neuronal and glial cell responses to nerve injury, and during regeneration, while taking account of the clinical requirements and practical limitations. The peripheral nervous system also provides a simpler model for nerve regeneration than the central nervous system, but with translational potential.
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| 13. |
- Jones, Rebecca M., et al.
(författare)
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Surgical treatment of a Morel-Lavallee lesion of the distal thigh with the use of lymphatic mapping and fibrin sealant
- 2012
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Ingår i: Journal of Plastic, Reconstructive & Aesthetic Surgery. - : Elsevier BV. - 1748-6815 .- 1878-0539. ; 65:11, s. 1589-1591
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A Morel-Lavallee lesion can occur after a closed degloving injury. It is a persistent seroma that may be resistant to conservative methods of treatment such as percutaneous drainage and compression therapy. We present a novel, successful method of surgical treatment. Case report: A 70 year-old lady developed a 30 x 15 cm rapidly enlarging right medial thigh/knee swelling after being hit by a car. Conservative treatments failed, sarcoma was excluded, and the diagnosis confirmed, by MR imaging and cytology prior to referral. The lesion was excised, and blue dye lymphatic mapping used to identify and ligate feeding lymphatic vessels. The cavity was then closed using fibrin sealant spray and resorbable quilting sutures. A pressure garment was fitted. Result: The wound healed without complication, with no recurrence at six months. The patient returned to normal activities without pressure garments. Conclusion: This method provides a novel, successful approach to the surgical treatment of a chronic Morel-Lavallee lesion. (c) 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
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| 14. |
- Kirby, Andrew, et al.
(författare)
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Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:3, s. 299-303
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Tidskriftsartikel (refereegranskat)abstract
- Although genetic lesions responsible for some mendelian disorders can be rapidly discovered through massively parallel sequencing of whole genomes or exomes, not all diseases readily yield to such efforts. We describe the illustrative case of the simple mendelian disorder medullary cystic kidney disease type 1 (MCKD1), mapped more than a decade ago to a 2-Mb region on chromosome 1. Ultimately, only by cloning, capillary sequencing and de novo assembly did we find that each of six families with MCKD1 harbors an equivalent but apparently independently arising mutation in sequence markedly under-represented in massively parallel sequencing data: the insertion of a single cytosine in one copy (but a different copy in each family) of the repeat unit comprising the extremely long (similar to 1.5-5 kb), GC-rich (>80%) coding variable-number tandem repeat (VNTR) sequence in the MUC1 gene encoding mucin 1. These results provide a cautionary tale about the challenges in identifying the genes responsible for mendelian, let alone more complex, disorders through massively parallel sequencing.
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| 15. |
- Terenghi, Giorgio, et al.
(författare)
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The nerve injury and the dying neurons : diagnosis and prevention
- 2011
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Ingår i: Journal of hand surgery. European volume. - Oxford : Churchill Livingstone. - 1753-1934 .- 2043-6289. ; 36E:9, s. 730-734
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Forskningsöversikt (refereegranskat)abstract
- Following distal nerve injury significant sensory neuronal cell death occurs in the dorsal root ganglia, while after a more proximal injury, such as brachial plexus injury, a sizeable proportion of spinal motoneurons also undergo cell death. This phenomenon has been undervalued for a long time, but it has a significant role in the lack of functional recuperation, as neuronal cells cannot divide and be replaced, hence the resulting nerve regeneration is usually suboptimal. It is now accepted that this cell death is due to apoptosis, as indicated by analysis of specific genes involved in the apoptotic signalling cascade. Immediate nerve repair, either by direct suturing or nerve grafting, gives a degree of neuroprotection, but this approach does not fully prevent neuronal cell death and importantly it is not always possible. Our work has shown that pharmacological intervention using either acetyl-L-carnitine (ALCAR) or N-acetyl-cysteine (NAC) give complete neuroprotection in different types of peripheral nerve injury. Both compounds are clinically safe and experimental work has defined the best dose, timing after injury and duration of administration. The efficacy of neuroprotection of ALCAR and NAC can be monitored non-invasively using MRI, as demonstrated experimentally and more recently by clinical studies of the volume of dorsal root ganglia. Translation to patients of this pharmacological intervention requires further work, but the available results indicate that this approach will help to secure a better functional outcome following peripheral nerve injury and repair.
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| 16. |
- van Schaik, Fiona D. M., et al.
(författare)
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Serological markers predict inflammatory bowel disease years before the diagnosis
- 2013
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 62:5, s. 683-688
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Tidskriftsartikel (refereegranskat)abstract
- Objective Anti-neutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae mannan antibodies (ASCAs) have been detected in the serum of patients with ulcerative colitis (UC) and Crohn's disease (CD) and their unaffected family members. The aim of this study was to establish the value of serological markers as predictors of UC and CD. Design Individuals who developed CD or UC were identified from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. At recruitment, none of the participants had a diagnosis of CD or UC. For each incident case, two controls were randomly selected matched for centre, date of birth, sex, date of recruitment and time of follow-up. Serum of cases and controls obtained at recruitment were analysed for ASCA IgG, ASCA IgA, perinuclear anti-neutrophil cytoplasmic antibody (pANCA), antibodies against Escherichia coli outer membrane porin C (OmpC) and flagellin CBir1. Conditional logistic regression was used to determine risk of CD and UC. Receiver operating characteristic curves were constructed to test accuracy. Results A total of 77 individuals were diagnosed with CD and 167 with UC after a mean follow-up of 4.5 (SD 3.2) and 4.4 (SD 3.1) years following blood collection, respectively. Combinations of pANCA, ASCA, anti-CBir1 and anti-OmpC were most accurate in predicting incident CD and UC (area under curve 0.679 and 0.657, respectively). The predictive value of the combination of markers increased when time to diagnosis of CD or UC decreased. Conclusion A panel of serological markers is able to predict development of CD and UC in individuals from a low-risk population.
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| 17. |
- West, Christian Alexander, et al.
(författare)
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Sensory neuron death after upper limb nerve injury and protective effect of repair : clinical evaluation using volumetric magnetic resonance imaging of dorsal root Ganglia.
- 2013
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Ingår i: Neurosurgery. - 0148-396X .- 1524-4040. ; 73:4, s. 632-640
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Extensive death of sensory neurons after nerve trauma depletes the number of regenerating neurons, contributing to inadequate cutaneous innervation density and poor sensory recovery. Experimentally proven neuroprotective neoadjuvant drugs require noninvasive in vivo measures of neuron death to permit clinical trials. In animal models of nerve transection, magnetic resonance imaging (MRI) proved a valid tool for quantifying sensory neuron loss within dorsal root ganglia (DRG) by measuring consequent proportional shrinkage of respective ganglia.OBJECTIVE: This system is investigated for clinical application after upper limb nerve injury and microsurgical nerve repair.METHODS: A 3-T clinical magnet was used to image and measure volume (Cavalieri principle) of C7-T1 DRG in uninjured volunteers (controls, n = 14), hand amputees (unrepaired nerve injury, n = 5), and early nerve repair patients (median and ulnar nerves transected, microsurgical nerve repair within 24 hours, n = 4).RESULTS: MRI was well tolerated. Volumetric analysis was feasible in 74% of patients. A mean 14% volume reduction was found in amputees' C7 and C8 DRG (P < .001 vs controls). Volume loss was lower in median and ulnar nerve repair patients (mean 3% volume loss, P < .01 vs amputees), and varied among patients. T1 DRG volume remained unaffected.CONCLUSION: MRI provides noninvasive in vivo assessment of DRG volume as a proxy clinical measure of sensory neuron death. The significant decrease found after unrepaired nerve injury provides indirect clinical evidence of axotomy-induced neuronal death. This loss was less after nerve repair, indicating a neuroprotective benefit of early repair. Volumetric MRI has potential diagnostic applications and is a quantitative tool for clinical trials of neuroprotective therapies.
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| 18. |
- West, Christian Alexander, et al.
(författare)
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Sensory Neurons of the Human Brachial Plexus : A Quantitative Study Employing Optical Fractionation and In-Vivo Volumetric Magnetic Resonance Imaging.
- 2012
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Ingår i: Neurosurgery. - Philadelphia : Lippincott Williams & Wilkins. - 0148-396X .- 1524-4040. ; 70:5, s. 1183-1194
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Extensive neuron death following peripheral nerve trauma is implicated in poor sensory recovery. Translational research for experimentally proven neuroprotective drugs requires knowledge of the numbers and distribution of sensory neurons in the human upper limb, and a novel non-invasive clinical measure of neuron loss. OBJECTIVE: To compare optical fractionation and volumetric MRI of dorsal root ganglia (DRG) in histological quantification and objective clinical assessment of human brachial plexus sensory neurons. METHODS: Bilateral C5-T1 DRG were harvested from 5 human cadavers for stereological volume measurement and sensory neuron counts (optical fractionator). MRI scans were obtained from 14 normal volunteers for volumetric analysis of C5-T1 DRG. RESULTS: 425,409 (SD 15,596) sensory neurons innervate the brachial plexus with a significant difference in neuron counts and DRG volume between segmental levels (p<0.0001), with C7 ganglion containing the most. DRG volume correlated with neuron counts (r=0.75, p<.001). Vertebral artery pulsation hindered C5&6 imaging, yet high resolution MRI of C7, C8 and T1 DRG permitted unbiased volume measurement. In accord with histological analysis, MRI confirmed a significant difference between C7, C8 and T1 DRG volume (p<.001), inter-individual variability (COV 15.3%), and sex differences (p=.04). Slight right-left (R/L) sided disparity in neuron counts (2.5%, p=.04) was possibly related to hand dominance, but no significant volume disparity existed. CONCLUSION: Neuron counts for the human brachial plexus are presented. These correlate with histological DRG volumes and concur with volumetric MRI results in human volunteers. Volumetric MRI of C7-T1 DRG is a legitimate non-invasive proxy measure of sensory neurons for clinical study.
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| 19. |
- Zetlitz, Elisabeth, et al.
(författare)
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Objective Assessment of Surgical Training in Flexor Tendon Repair : The Utility of a Low-Cost Porcine Model as Demonstrated by a Single-Subject Research Design
- 2012
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Ingår i: Journal of Surgical Education. - : Elsevier BV. - 1931-7204. ; 69:4, s. 504-510
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study evaluated the utility of a porcine flexor tendon model and standard biomechanical testing procedures to quantify the acquisition of surgical skills associated with Zone II flexor tendon repair in a trainee by benchmarking task performance outcomes relative to evidence-based standards. STUDY DESIGN: Single-subject repeated measures research design. Bench-top set-up of apparatus undertaken in a University Research laboratory. After initial directed learning, a trainee repaired 70 fresh flexor digitorum profundus tendons within the flexor sheath using either a Pennington or ventral-locking-loop modification of a two-strand Kessler core repair. Tendon repairs were then preconditioned and distracted to failure. Key biomechanical parameters of the repair, including the ultimate tensile strength (UTS), yield strength, 3 mm gap force and stiffness, were calculated. Repairs were divided into 3 categories, early (first 10 days), intermediate (ensuing 10 days), and late repairs (final 10 days), and potential changes in repair properties over the training period were evaluated using a general linear modeling approach. RESULTS: There was a significant change in the mechanical characteristics of the repairs over the training period, evidencing a clear learning effect (p < 0.05). Irrespective of the repair technique employed, early and intermediate repairs were characterized by a significantly lower UTS (29% and 20%, respectively), 3 mm gap (21% and 16%, respectively), and yield force (18% and 23%, respectively), but had a higher stiffness (33% and 38%, respectively) than late repairs (p < 0.05). The UTS of late repairs (47-48 N) were comparable to those published within the literature (45-51 N), suggesting surgical competence of the trainee. CONCLUSIONS: This simple, low-cost porcine model appears to be useful for providing preclinical training in flexor tendon repair techniques and has the potential to provide a quantitative index to evaluate the competency of surgical trainees. Further research is now required to identify optimal training parameters for flexor tendon repair and to develop procedure-specific standards for adequate benchmarking.
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