Manipulation of distal radius fractures: a comparison of Bier's block vs haematoma block.

INTRODUCTION: Displaced distal radius fractures often require manipulation under anaesthesia. Many anaesthetic techniques are described, with the two most commonly used being Bier's block (BB) and haematoma block (HB). Despite national guidance preferring a BB, an HB is often performed instead. This study aims to compare the analgesic properties of a BB with those of an HB when manipulating distal radius fractures. METHODS: This is an observational cohort study comparing the management of displaced distal radius fractures requiring reduction across two National Health Service trusts. Patients aged over 18 with isolated, displaced distal radius fractures were recruited. Patient demographics, AO fracture classification and grade of clinician performing the procedure were recorded. A numeric rating scale (NRS) pain score was obtained for each patient after manipulation. The quality of reduction was judged against standardised anatomical parameters. RESULTS: Some 200 patients were recruited (100 HB, 100 BB). There were no differences in age (BB: median 66.5 years, interquartile range [IQR] 55-74; HB: median 67 years, IQR 55-74; p = 0.79) or fracture characteristics (p = 0.29) between cohorts. Patients undergoing BB had significantly lower pain scores with a lower IQR than those undergoing HB (p < 0.005). Patients undergoing BB manipulation were more likely to have the fracture reduced and normal anatomy restored (p < 0.005). BBs were performed mainly by Foundation Year 2 junior doctors, whereas HB manipulations were performed by a range of clinicians from emergency nurse practitioners to consultants. CONCLUSIONS: BB provides better analgesia than an HB. This can be performed successfully and reliably by Senior House Officer-level junior doctors.

Biological mesh is a safe and effective method of abdominal wall reconstruction in cytoreductive surgery for peritoneal malignancy.

BACKGROUND: Patients with peritoneal malignancy often have multiple laparotomies before referral for cytoreductive surgery (CRS). Some have substantial abdominal wall herniation and tumour infiltration of abdominal incisions. CRS involves complete macroscopic tumour removal and hyperthermic intraperitoneal chemotherapy (HIPEC). Abdominal wall reconstruction is problematic in these patients. The aim of this study was to establish immediate and long-term outcomes of abdominal wall reconstruction with biological mesh in a single centre. METHODS: A dedicated peritoneal malignancy database was searched for all patients who had biological mesh abdominal wall reconstruction between 2004 and 2015. Short- and long-term outcomes were reviewed. All patients had annual abdominal CT as routine peritoneal malignancy follow-up. RESULTS: Some 33 patients (22 women) with a mean age of 53·4 (range 19-82) years underwent abdominal wall reconstruction with biological mesh. The majority (23) had CRS for pseudomyxoma (19 low grade), six for colorectal peritoneal metastasis and four for appendiceal adenocarcinoma; 18 had undergone CRS and HIPEC previously. Twenty-five of the 33 patients had abdominal wall tumour involvement and eight had concurrent hernias. The mean duration of surgery was 486 (range 120-795) min and the mean mesh size used was 345 (50-654) cm2. Ten patients developed wound infections and four had a seroma. Two developed early enterocutaneous fistulas. Mean follow-up was 48 months. Five patients developed an incisional hernia. Four died from progressive malignancy. A further 15 patients had disease recurrence, but only one had isolated abdominal wall recurrence. CONCLUSION: Biological mesh was safe and effective for abdominal wall reconstruction in peritoneal malignancy. Postoperative wound infections were frequent but nevertheless incisional hernia rates were low with no instances of mesh-related bowel erosion or fistulation.

Eomesodermin-At Dawn of Cell Fate Decisions During Early Embryogenesis.

Proteins of the large family of T-box transcription factors are implicated in a broad spectrum of developmental processes. Loss-of-function mutations of T-box(Tbx) factors frequently cause severe embryonic phenotypes, often resulting from defects in cell fate specification and lineage differentiation. This review summarizes current knowledge on the functions of the T-box transcription factor Eomesodermin (Eomes) from postfertilization development until gastrulation stages of vertebrate embryos. Eomes exhibits evolutionary conserved functions in cell lineage specification and morphogenesis during gastrulation in all studied vertebrate model systems. In addition, during mammalian embryogenesis, Eomes is crucially required in extraembryonic tissues that are specific for intrauterine development. This chapter mainly focuses on mammalian development of mouse; however, common functions shared among other vertebrate model system, such as embryos of zebrafish and Xenopus laevis, will be compared in the context of specification cell lineages during gastrulation. Furthermore, this review recapitulates the current understanding of the molecular functions and transcriptional targets of Eomes as component of transcriptional complexes that guide cell-type specification and morphogenesis of early vertebrate embryos.

Three difficult cases: the challenge of autoimmunity, immunodeficiency and recurrent infections in patients with Good syndrome.

Good syndrome (GS) is a rare, adult-acquired primary combined immunodeficiency syndrome arising in the context of previous or current thymoma. Patients with GS frequently develop recurrent sinopulmonary infections and are also at high risk of autoimmune manifestations, including skin conditions such as lichen planus. We report three middle-aged patients with GS complicated by multiple autoimmune and infectious manifestations. The combination of immunodeficiency, autoimmunity and recurrent infections seen in patients with GS continues to present a management challenge, particularly in patients with oral mucosal disease and recurrent candidiasis. Clinicians should be prompted to investigate an underlying immunodeficiency in patients with multiple autoimmune conditions and recurrent sinopulmonary infections.

The effects of stochastic and episodic movement of the optimum on the evolution of the G-matrix and the response of the trait mean to selection.

Theoretical and empirical results demonstrate that the G-matrix, which summarizes additive genetic variances and covariances of quantitative traits, changes over time. Such evolution and fluctuation of the G-matrix could potentially have wide-ranging effects on phenotypic evolution. Nevertheless, no studies have yet addressed G-matrix stability and evolution when movement of an intermediate optimum includes large, episodic jumps or stochasticity. Here, we investigate such scenarios by using simulation-based models of G-matrix evolution. These analyses yield four important insights regarding the evolution and stability of the G-matrix. (i) Regardless of the model of peak movement, a moving optimum causes the G-matrix to orient towards the direction of net peak movement, so that genetic variance is enhanced in that direction (the variance enhancement effect). (ii) Peak movement skews the distribution of breeding values in the direction of movement, which impedes the response to selection. (iii) The stability of the G-matrix is affected by the overall magnitude and direction of peak movement, but modes and rates of peak movement have surprisingly small effects (the invariance principle). (iv) Both episodic and stochastic peak movement increase the probability that a population will fall below its carrying capacity and go extinct. We also present novel equations for the response of the trait mean to multivariate selection, which take into account the higher moments of the distribution of breeding values.

The majority of colorectal resections require an open approach, even in units with a special interest in laparoscopic surgery.

AIM: Proponents suggest that laparoscopic colorectal resection might be achievable in up to 90% of cases, while keeping conversion rates below 10%. This unselected prospective case series reports on the proportion of patients having a completed laparoscopic colorectal resection in two units where laparoscopic colorectal practice is well established and readily available. METHOD: All patients undergoing elective and emergency colorectal resection during a 6-month period were identified. The underlying pathology and the surgical approach (laparoscopic or open) were recorded. The contraindications to laparoscopic resection were also documented. The need and rationale for conversion to an open approach were recorded. RESULTS: In total, 205 consecutive patients (160 elective and 45 emergency procedures) underwent colorectal resection for malignancy [117 (57%) patients] and benign pathology [88 (43%) patients]. Laparoscopic resection was attempted in 127/205 (62%) patients and 31/127 (24%) of these were converted to open surgery. The main reasons for not attempting laparoscopic resection were locally advanced disease and emergency surgery. The commonest reasons for conversion were advanced disease and to allow completion of rectal dissection and/or cross-stapling of the rectum. CONCLUSION: Despite a special interest in laparoscopic colorectal surgery of the two colorectal units who provided the data for this study, fewer than half (96/205; 47%) of the patients in this consecutive unselected series who were undergoing major colorectal resection had the procedure completed laparoscopically.

The impact of stenting obstructing colorectal tumours in a district general hospital.

INTRODUCTION: The technique of stenting malignant obstructing colorectal lesions is established as an acceptable treatment with a low morbidity and mortality. This paper reviews our experience in stenting malignant colorectal obstruction and compares this group with those who underwent emergency surgery as their primary intervention. METHODS: A retrospectively kept database over four years was reviewed and patients who had undergone either stenting or emergency surgery for a malignant colorectal obstruction were identified. These patients' notes were retrieved and reviewed. RESULTS: During the duration of study, a total of 29 stents were placed in 28 patients, with a mean age of 78 y (range 59-96 years). Patients generally had significant co-existing morbidity, with a median ASA score of 2.5. The timing of stent placement was a mean of 3.4 days (1-9 days) after presentation, including time for relevant investigation and diagnosis. Mean length of hospital stay was 9.8 days (2-36 days). In the emergency operation category, during the period of study, a total of 38 patients had operations for large bowel obstruction, either because the lesion was not suitable for stenting, or the personnel for stenting were not available. These patients ranged in age from 45 to 96 years, with a mean age of 72.4 years. Patients in this group were generally a little fitter than the stented group, with a median ASA grade of 2, and 14/38 patients were ASA1 (the largest group). Despite this Post-operative recovery was slow with these patients, the average length of stay being 16 days (range 8-66 days). CONCLUSIONS: In this study, we report our data on the first four years of stenting malignant bowel obstruction. It is a feasible and acceptable means of treatment, and we have demonstrated comparable morbidity and mortality to that reported in medical literature. The technique may avoid the need for emergency operation with its concomitant risks, lengthy in-patient stay, and high likelihood for a stoma. We would advocate the use of self expanding metal stents where appropriate in the management of large bowel obstruction.

Adaptive divergence within and between ecotypes of the terrestrial garter snake, Thamnophis elegans, assessed with F(ST)-Q(ST) comparisons.

Populations of the terrestrial garter snake (Thamnophis elegans) around Eagle Lake in California exhibit dramatic ecotypic differentiation in life history, colouration and morphology across distances as small as a few kilometres. We assayed the role of selection in ecotypic differentiation in T. elegans using F(ST)-Q(ST) analysis and identified selective agents using direct and indirect observations. We extended the conventional implementation of the F(ST)-Q(ST) approach by using three-level analyses of genetic and phenotypic variance to assess the role of selection in differentiating populations both within and between ecotypes. These results suggest that selection has driven differentiation between as well as within ecotypes, and in the presence of moderate to high gene flow. Our findings are discussed in the context of previous correlational selection analyses which revealed stabilizing and correlational selection for some of the traits examined.

Introduction to the DAPPLE Air Pollution Project.

The Dispersion of Air Pollution and its Penetration into the Local Environment (DAPPLE) project brings together a multidisciplinary research group that is undertaking field measurements, wind tunnel modelling and computer simulations in order to provide better understanding of the physical processes affecting street and neighbourhood-scale flow of air, traffic and people, and their corresponding interactions with the dispersion of pollutants at street canyon intersections. The street canyon intersection is of interest as it provides the basic case study to demonstrate most of the factors that will apply in a wide range of urban situations. The aims of this paper are to introduce the background of the DAPPLE project, the study design and methodology for data collection, some preliminary results from the first field campaign in central London (28 April-24 May 2003) and the future for this work. Updated information and contact details are available on the web site at http://www.dapple.org.uk.

Molecular systematics and evolution of Regina and the thamnophiine snakes.

Snakes of the tribe Thamnophiini represent an ecologically important component of the herpetofauna in a range of habitats across North America. Thamnophiines are the best-studied colubrids, yet little is known of their systematic relationships. A molecular phylogenetic study of 32 thamnophiine species using three complete mitochondrial genes (cytochrome b, NADH dehydrogenase subunit 2, and 12S ribosomal DNA) recovered a well-supported phylogeny with three major clades: a garter snake group, a water snake group, and a novel semifossorial group. The historically contentious genus Regina, which contains the crayfish-eating snakes, is polyphyletic. The phylogeographic pattern of Thamnophis is consistent with an hypothesis of at least one invasion of northern North America from Mexico.

The adaptive landscape as a conceptual bridge between micro- and macroevolution.

An adaptive landscape concept outlined by G.G. Simpson constitutes the major conceptual bridge between the fields of micro- and macroevolutionary study. Despite some important theoretical extensions since 1944, this conceptual bridge has been ignored in many empirical studies. In this article, we review the status of theoretical work and emphasize the importance of models for peak movement. Although much theoretical work has been devoted to evolution on stationary, unchanging landscapes, an important new development is a focus on the evolution of the landscape itself. We also sketch an agenda of empirical issues that is inspired by theoretical developments.

The Bateman gradient and the cause of sexual selection in a sex-role-reversed pipefish.

As a conspicuous evolutionary mechanism, sexual selection has received much attention from theorists and empiricists. Although the importance of the mating system to sexual selection has long been appreciated, the precise relationship remains obscure. In a classic experimental study based on parentage assessment using visible genetic markers, more than 50 years ago A. J. Bateman proposed that the cause of sexual selection in Drosophila is 'the stronger correlation, in males (relative to females), between number of mates and fertility (number of progeny)'. Half a century later, molecular genetic techniques for assigning parentage now permit mirror-image experimental tests of the 'Bateman gradient' using sex-role-reversed species. Here we show that, in the male-pregnant pipefish Syngnathus typhle, females exhibit a stronger positive association between number of mates and fertility than do males and that this relationship responds in the predicted fashion to changes in the adult sex ratio. These findings give empirical support to the idea that the relationship between mating success and number of progeny, as characterized by the Bateman gradient, is a central feature of the genetic mating system affecting the strength and direction of sexual selection.

Brachyury is a target gene of the Wnt/beta-catenin signaling pathway.

To identify target genes of the Wnt/beta-catenin signaling pathway in early mouse embryonic development we have established a co-culture system consisting of NIH3T3 fibroblasts expressing different Wnts as feeder layer cells and embryonic stem (ES) cells expressing a green fluorescent protein (GFP) reporter gene transcriptionally regulated by the TCF/beta-catenin complex. ES cells specifically respond to Wnt signal as monitored by GFP expression. In GFP-positive ES cells we observe expression of Brachyury. Two TCF binding sites located in a 500 bp Brachyury promoter fragment bind the LEF-1/beta-catenin complex and respond specifically to beta-catenin-dependent transactivation. From these results we conclude that Brachyury is a target gene for Wnt/beta-catenin signaling.

Disseminated toxoplasmosis. Unusual presentations in the immunocompromised host.

OBJECTIVE: Owing to the increasing number of patients with acquired immunodeficiency syndrome and immunosuppressed transplant patients, disseminated Toxoplasma gondii has emerged as a potentially fatal pathogen. Common presentations include encephalitis, pneumonia, and myocarditis. The objective of this report is to describe the clinical course, histologic features, and outcome in two immunocompromised patients with disseminated toxoplasmosis presenting with parasitemia and panniculitis. MATERIALS AND METHODS: Two cases of disseminated toxoplasmosis presenting with parasitemia (patient 1) and panniculitis (patient 2) were retrieved from the clinical, surgical, and autopsy pathology archives of Vanderbilt University Medical Center, Nashville, Tenn. The histology and diagnostic approaches used are reported. Charts were reviewed for primary diagnosis, therapy protocols, clinical presentation of infection, and outcome. RESULTS: Patient 1 developed a clinically unexplained sepsis syndrome shortly after heart transplantation; T gondii parasitemia was diagnosed by examination of peripheral blood smears. The diagnosis was confirmed at autopsy. Patient 2 was a child undergoing induction chemotherapy for lymphoma who developed rapidly progressive neurologic deterioration accompanied by a maculopapular skin rash; T gondii panniculitis was diagnosed retrospectively when histologic examination was combined with immunohistochemistry. Autopsies performed in both cases confirmed widely disseminated infection. CONCLUSIONS: Disseminated toxoplasmosis should be considered in the differential diagnosis of immunocompromised patients with culture-negative sepsis syndrome, particularly if combined with neurologic, respiratory, or unexplained skin lesions. Examination of Wright's-stained peripheral blood smears or antitoxoplasma immunoperoxidase studies of skin biopsies may be diagnostic and allow rapid initiation of antibiotic therapy. Autopsy findings contributed to both of our cases by documenting the wide-spread heavy parasite burden and demonstrating numerous diagnostic T gondii cyst forms.

Unrecognized congenital posterior urethral minivalves in men.

Removal of small congenital posterior urethral valves, unrecognized in prior urologic investigations of 10 men, relieved "prostatic" symptoms in 9. In follow-ups (5-20 years, average 12.5 years), 3 have experienced a recurrence attributed to bladder neck obstruction in 2 and to unknown causes in 1. Bladder neck incision carried out in 2, cured 1. The other was lost to follow-up.