Distal radius fracture: epidemiology, outcome, and the prediction of instability

INTRODUCTION: Distal radius fracture as an injury appeared in the literature 2400 years ago. It was only recognised as a fracture 220 years ago. That it was not a benign fracture was only recognised 60 years ago. Attempts to improve the surgical treatment of the fracture have only been in the last two or three decades. The introduction of this thesis outlines the history of distal radius fracture, describes the relevant anatomy, and describes the methods used to classify and measure the fracture. The aims of the thesis are presented with respect to the main deficiencies in our strategies for the management of the fracture, namely an inability to predict how the fracture will behave.MATERIALS AND METHODS: The studies in the thesis are divided into two broad sections. The first section is descriptive. Data were collected prospectively over a five-and-one-half year period for approximately 4000 fractures. Validation of the data is performed. The data are used to describe the epidemiology of the fracture in the Lothian Region, and the anatomical outcome of the fracture. Multiple logistic regression analysis of the data is performed to identify those factors (recordable at patient presentation) that are prognostic of outcome. The statistical method used provides weighted significance for each of these factors, and thus mathematical formulae predictive of outcome are constructable. A number of formulae are produced, depending on the displacement of the fracture at presentation (minimally displaced or displaced), and on the outcome measure (early and late instability, the risk of malunion, and carpal malalignment). The second section is validative. The studies in this section are an assessment of the performance of the mathematical formulae in the clinical setting. In the first study, data are collected prospectively for 139 patients, and outcomes recorded. Blinded to outcome, the formulae are applied to each patient's data to calculate the percentage risk of poor outcome. The sensitivity and specificity of mathematical prediction of outcome are calculated. In the second study, a group of clinicians involved in fracture management are asked to predict fracture outcome using first clinical experience and then the predictive formula. This is done using forty radiographs of displaced fractures of known outcome. The two methods of prediction are then compared.RESULTS: The distal radius fracture occurred predominately in the older female patient following a simple fall. The fracture in this typical patient was usually unstable. The most consistently important predictors of fracture outcome were patient age, fracture displacement, comminution and ulnar variance. The mathematical formulae were able to correctly predict anatomical outcome in approximately 7/10 patients in the validative study. This was a significant improvement upon the predictive accuracy of the clinicians using experience alone. Use of the predictive formula also significantly reduced inter-observer variation in the assessment of fracture stability.CONCLUSION: Use of the predictive formula in the Accident & Emergency setting could improve decision-making in fracture management. By promoting an assessment of fracture stability rather than fracture displacement, appropriate management choices are facilitated. The unstable fracture can be referred for operative management, and ineffective closed reduction avoided. The thesis also demonstrates the potential value of the method employed. Multiple logistic regression analysis may provide a guide to treatment where the management of the condition is dependent upon the natural history

Monoartritis gotosa de muñeca asociada a necrosis del semilunar: a propósito de un caso clínico

Se presenta un caso de monoartritis de muñeca asociada a imágenes radiológicas de necrosis avascular del semilunar que, tras biopsia de la sinovial, se diagnostica de artritis gotosa. Esta asociación es rara. La alteración metabólica que se produce en la gota da lugar a una sinovitis, que provoca un aumento de presión intraarticular. Esta hiperpresión en el carpo podría determinar una necrosis isquémica del semilunar, pero con una evolución diferente a la enfermedad de Kienböck. Es por ello que una artropatía metabólica, debe considerarse como diagnóstico diferencial con la enfermedad de Kiemböck cuando se asocian imágenes geódicas en el carpo y radio.We report a case of monoarthritis of the wrist associated with radiological signs of avascular necrosis of lunate. The synovial biopsy confirmed the diagnosis of gout. This is a very rare association. Differential diagnosis should be make with a metabolic arthritis when bone necrosis is associated with osseous lesions in carpal bones and radius

International consensus guideline for reporting transmission electron microscopy results in the diagnosis of Primary Ciliary Dyskinesia (BEAT PCD TEM Criteria)

Primary Ciliary Dyskinesia (PCD) is a heterogeneous genetic condition. European and North American diagnostic guidelines recommend transmission electron microscopy (TEM) as one of a combination of tests to confirm a diagnosis. However, there is no definition of what constitutes a defect or consensus on reporting terminology. The aim of this project was to provide an internationally agreed ultrastructural classification for PCD diagnosis by TEM. A consensus guideline was developed by PCD electron microscopy experts representing 18 centres in 14 countries. An initial meeting and discussion were followed by a Delphi consensus process. The agreed guideline was then tested, modified and retested through exchange of samples and electron micrographs between the 18 diagnostic centres. The final guideline a) Provides agreed terminology and a definition of class 1 defects which are diagnostic for PCD; b) Identifies class 2 defects which can indicate a diagnosis of PCD in combination with other supporting evidence; c) Describes features which should be included in a ciliary ultrastructure report to assist multidisciplinary diagnosis of PCD d) Defines adequacy of a diagnostic sample. This tested and externally validated statement provides a clear guideline for the diagnosis of PCD by TEM which can be used to standardise diagnosis internationally.</p

Treatment of reducible unstable fractures of the distal radius in adults: a randomised controlled trial of De Palma percutaneous pinning versus bridging external fixation

Background: At present, there is no conclusive evidence regarding the best treatment method for reducible unstable fractures of the distal radius. This study compared the effectiveness of two methods used in surgical treatment of such fractures: percutaneous pinning and external fixation.Methods: We randomly allocated 100 patients into two groups treated surgically with modified de Palma percutaneous pinning and bridging external fixation. Independent but not blinded evaluators administered the DASH quality-of-life questionnaire at postoperative months 6 and 24, performed functional assessment of pain, range of motion, and palm grip strength, and radiographic examinations (volar and radial angle, and height of the radius) before the operation, immediately afterwards, and at 6 and 24 months postoperative. Modified de Palma percutaneous pinning patients used an above-elbow cast whereas external fixation group had unrestricted elbow motion after surgery. Patients who for any reason demonstrated treatment failure or required additional interventions were followed up and their results were included in the group into which these patients had initially been randomised according to the intention-to-treat principle. A significance level of 5% (alpha = 0.05). was used for all statistical tests, such that tests presenting a p-value less than 0.05 were considered statistically significant.Results: Ninety one (58.8 mean age and 66 participants were female) were included in the final assessment at 24 months. the DASH questionnaire evaluation showed a statistically significant result favouring the de Palma group (mean difference = -7.1 p = 0.044) after six months, but this was not maintained at 24 months. There were no statistically differences between the groups with respect to palm grip strength. Analysis of the range-of-motion limitation index (uninjured side minus affected side motion of) showed a statistical difference (mean difference = 2.4 p = 0.043) favoring the external fixator group with regard to the supination movement 6 months after the operation; however, this was not maintained at 24 months. the final results of the radiographic evaluation were similar for the two groups. Overall, five patients developed complications: two with de Palma pinning and three with external fixation.Conclusion: There was a small statistically significant difference favouring the de Palma method in early functional at 6 months according to the DASH questionnaire, and for supination movement favouring the fixator group. However, both were not clinical relevant. By 24 months the groups were similar for all outcome

Functional redundancy between DNA ligases I and III in DNA replication in vertebrate cells

In eukaryotes, the three families of ATP-dependent DNA ligases are associated with specific functions in DNA metabolism. DNA ligase I (LigI) catalyzes Okazaki-fragment ligation at the replication fork and nucleotide excision repair (NER). DNA ligase IV (LigIV) mediates repair of DNA double strand breaks (DSB) via the canonical non-homologous end-joining (NHEJ) pathway. The evolutionary younger DNA ligase III (LigIII) is restricted to higher eukaryotes and has been associated with base excision (BER) and single strand break repair (SSBR). Here, using conditional knockout strategies for LIG3 and concomitant inactivation of the LIG1 and LIG4 genes, we show that in DT40 cells LigIII efficiently supports semi-conservative DNA replication. Our observations demonstrate a high functional versatility for the evolutionary new LigIII in DNA replication and mitochondrial metabolism, and suggest the presence of an alternative pathway for Okazaki fragment ligation

Mapping and Use of a Sequence that Targets DNA Ligase I to Sites of DNA Replication In Vivo

The mammalian nucleus is highly organized, and nuclear processes such as DNA replication occur in discrete nuclear foci, a phenomenon often termed “functional organization” of the nucleus. We describe the identification and characterization of a bipartite targeting sequence (amino acids 1–28 and 111–179) that is necessary and sufficient to direct DNA ligase I to nuclear replication foci during S phase. This targeting sequence is located within the regulatory, NH2-terminal domain of the protein and is dispensable for enzyme activity in vitro but is required in vivo. The targeting domain functions position independently at either the NH2 or the COOH termini of heterologous proteins