Publications by authors named "Werken C"

In mouse female preimplantation embryos, the paternal X chromosome (Xp) is silenced by imprinted X chromosome inactivation (iXCI). This requires production of the noncoding Xist RNA in cis, from the Xp. The Xist locus on the maternally inherited X chromosome (Xm) is refractory to activation due to the presence of an imprint.

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Study Question: Are the kinase feedback loops that regulate activation and centromeric targeting of the chromosomal passenger complex (CPC), functional during mitosis in human embryos?

Summary Answer: Investigation of the regulatory kinase pathways involved in centromeric CPC targeting revealed normal phosphorylation dynamics of histone H2A at T120 (H2ApT120) by Bub1 kinase and subsequent recruitment of Shugoshin, but phosphorylation of histone H3 at threonine 3 (H3pT3) by Haspin failed to show the expected centromeric enrichment on metaphase chromosomes in the zygote.

What Is Known Already: Human cleavage stage embryos show high levels of chromosomal instability. What causes this high error rate is unknown, as mechanisms used to ensure proper chromosome segregation in mammalian embryos are poorly described.

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The different configurations of maternal and paternal chromatin, acquired during oogenesis and spermatogenesis, have to be rearranged after fertilization to form a functional embryonic genome. In the paternal genome, nucleosomal chromatin domains are re-established after the protamine-to-histone exchange. We investigated the formation of constitutive heterochromatin (cHC) in human preimplantation embryos.

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Immunofluorescence has been widely used to study histone modification dynamics and chromosome-associated proteins that regulate the segregation of chromosomes during cell divisions. Since many of these regulatory proteins interact (in)directly to exert their proper function, it is of interest to detect these proteins simultaneously, to establish their spatiotemporal relation. However, the detection of multiple epitopes on the same material is limited by the availability of antibodies derived from different host species.

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Background: The clinical results of removal of metal implants after fracture healing are unknown and the question whether to remove or to leave them in is part of discussion worldwide. We present the design of a prospective clinical multicentre cohort study to determine the main indications for and expectations of implant removal, the influence on complaints, the incidence of surgery related complications and the socio-economic consequences of implant removal.

Methods/design: In a prospective multicentre clinical cohort study at least 200 patients with a healed fracture after osteosynthesis with a metal implant are included for analyzing the outcome after removal.

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Purpose: In a level 1 university trauma center, an explorative randomized controlled study was performed to compare soft tissue damage and functional outcome after antegrade femoral nailing through a trochanteric fossa (also known as piriform fossa) entry point to a greater trochanter entry point in patients with a femoral shaft fracture.

Materials And Methods: Nineteen patients were enrolled and randomly assigned to two nail insertion groups; ten patients were treated with an Unreamed Femoral Nail(®) (UFN, Synthes(®), Solothurn, Switzerland) inserted at the trochanteric fossa and nine patients were treated with an Antegrade Femoral Nail(®) (AFN, Synthes(®), Solothurn, Switzerland) inserted at the tip of the greater trochanter. The main outcome measures were pain, gait, nerve and muscle function, along with endurance.

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Background: Human embryos generated by IVF demonstrate a high incidence of chromosomal segregation errors during the cleavage divisions. To analyse underlying molecular mechanisms, we investigated the behaviour of the chromosomal passenger complex (CPC) in human oocytes and embryos. This important mitotic regulatory complex comprises the inner centromere protein (INCENP), survivin, borealin and Aurora B, or the meiotic kinase Aurora C.

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Objectives: This study was performed to explore the relationship between entry point-related soft tissue damage in antegrade femoral nailing and the functional outcome in patients with a proximal third femoral shaft fracture.

Design: Retrospective clinical trial.

Setting: Level I university trauma center.

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Background: Complications of acute Achilles tendon rupture treatment are considered to negatively influence outcome, but the relevance of these effects is largely unknown.

Purpose: The Achilles Tendon Total Rupture Score (ATRS) was used to determine level of disability in patients with minimally invasive surgical Achilles tendon rupture repair with a complicated postoperative course.

Study Design: Case series; Level of evidence, 4.

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Rerupture after treatment of acute Achilles tendon rupture is considered a serious complication. Yet data on long-term outcome after rerupture are limited. This study evaluated outcome after rerupture and compares it to a reference of uncomplicated cases.

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The aim of this study was to measure the effect of treatment of acute Achilles tendon ruptures on calf muscle strength recovery. Eighty-three patients with acute Achilles tendon rupture were randomly allocated to either minimally invasive surgery with functional after-treatment or conservative treatment by functional bracing. Calf muscle strength using isokinetic testing was evaluated at 3 months and after 6 or more months posttreatment.

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Objective: To assess among seriously injured accident victims whether change of the Triage Revised Trauma Score (T-RTS) between first assessment and arrival at the hospital independently predicts mortality.

Design: Prospective cohort study.

Methods: The study analysed data on 507 trauma patients with multiple injuries and with a Hospital Trauma Index-Injury Severity Score (HTI-ISS) of 16 or higher, who were presented directly by ambulance services to the Accident & Emergency Department of the University Medical Centre Utrecht (the Netherlands) in 1999 and 2000.

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Background: Bioresorbable implants for musculoskeletal injuries involving bone and ligaments in adults might have significant advantages compared to the conventionally used non-resorbable metal implants because they lead to a gradual transfer of the mechanical load from the implant to the healing bone and do not require a secondary removal operation. Tissue reactions may present a problem and bioresorbable screws are mechanically not as strong as their metal counterparts.

Objectives: To compare bioresorbable implants to non-resorbable implants with respect to functional outcome, wound infections, other complications and reoperation rate,in the fixation of bone fractures or re-attachment of soft tissue to bone.

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Objectives: Insertion of rigid uniplane bent femoral nails through the piriform fossa has been reported to cause neurovascular complications. New nails were designed for more lateral entry points. However, these may be associated with a higher risk of iatrogenic fractures.

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Antegrade intramedullary nailing is an accepted method of treatment for femoral shaft fractures. Entrance of the nail through the trochanteric fossa is currently recommended by some surgeons. This approach results in some cases, however, in loss of abduction strength and persistent pain.

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Background: Several randomised trials have been published on the effect of low-intensity pulsed ultrasound (LIPUS) on fracture healing in both distal radius and tibia fractures. Most studies showed a positive effect on time to clinical and radiological healing. We hypothesised that LIPUS has a beneficial effect on the healing of fresh clavicle fractures as well and studied its effect in non-operatively treated shaft fractures.

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Background: Surgical repair of acute Achilles tendon ruptures is considered superior to nonoperative treatment, but complications other than rerupture range up to 34%. Nonoperative treatment by functional bracing seems a promising alternative.

Hypothesis: Nonoperative treatment of acute Achilles tendon rupture with functional bracing reduces the number of complications compared with surgical treatment with a minimally invasive technique.

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The treatment of unstable trochanteric femoral fractures is still challenging. The ideal implant should be easy to handle, allow for immediate full weight-bearing postoperatively and should have sufficient purchase in the femoral head/neck-fragment to limit cut-outs due to varus-deviation and rotation. The proximal femoral nail antirotation (PFNA), designed by AO, is an intramedullary device with a helical blade rather than a screw for better purchase in the femoral head and was tested in a clinical study.

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Background: The routine removal of orthopaedic fixation devices after fracture healing remains an issue of debate. There are no evidence-based guidelines on this matter, and little is known on surgeons' practice and perceived effectiveness of implant removal in different clinical settings.

Methods: A 41-item questionnaire was distributed to 730 attendees of the AO Principles and Masters Courses of Operative Fracture Treatment in Davos, Switzerland, to assess their attitudes towards removal of different types of implants, and perceived benefits and risks with this common procedure.

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Objective: To assess the impact of major trauma on individual and population health.

Methods: Data from a regional trauma registry were used, including all trauma fatalities and nonfatal severely injured patients (injury severity score >15) in 1999 and 2000. The impact of fatalities was expressed in terms of years of life lost (YLL).

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Objective: To quantify the prevalence of return to work after major trauma, and to investigate the determinants of postinjury work status.

Design: Prospective cohort study.

Setting: University Medical Centre Utrecht, a level 1 trauma centre in the Netherlands.

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Objective: To determine which factors predict death occurring in trauma patients who are alive on arrival at hospital Design Prospective cohort study Method Data were collected from 507 trauma patients with multiple injuries, with a Hospital Trauma Index-Injury Severity Score of 16 or more, who were initially delivered by the Emergency Medical Services to the Emergency Department of the University Medical Centre Utrecht (UMCU) during the period 1999-2000.

Results: Univariate analysis showed that every year of age increase resulted in a 2% greater risk of death. If the patient had been intubated at the scene of the accident, this risk was increased 4.

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Objective: To determine which factors predict death occurring in trauma patients who are alive on arrival at hospital Design Prospective cohort study Method Data were collected from 507 trauma patients with multiple injuries, with a Hospital Trauma Index-Injury Severity Score of 16 or more, who were initially delivered by the Emergency Medical Services to the Emergency Department of the University Medical Centre Utrecht (UMCU) during the period 1999-2000.

Results: Univariate analysis showed that every year of age increase resulted in a 2% greater risk of death. If the patient had been intubated at the scene of the accident, this risk was increased 4.

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Background: Studies of the consequences of major trauma have traditionally focused on mortality rates. The aims of this study were, firstly, to investigate the long-term functional health status in a large, unselected group of severely injured patients and to compare this with normative data, and secondly, to explore relations between functional health status and personal and injury characteristics.

Methods: A prospective cohort study was performed at the University Medical Centre Utrecht (a level-1 trauma centre) in The Netherlands.

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Objective: To determine the background and consequences of failing to diagnose injuries in prehospital care.

Design: Prospective cohort study.

Method: Data were collected from 507 trauma patients with multiple injuries, and a Hospital trauma index-injury severity score of 16 or higher, who were delivered by the emergency ambulance service to the emergency department of the University Medical Centre Utrecht, the Netherlands, in 1999-2000.

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