Publications by authors named "David J Wilkinson"

Article Synopsis
  • Serine proteinase inhibitors (serpins) are proteins that play important roles in various biological processes, including blood coagulation and extracellular matrix remodeling.
  • This study reveals that SERPINA3, a specific serpin, is crucial for the differentiation of mesenchymal stem cells into chondrocytes during early cartilage development, showing increased expression during this process.
  • Silencing SERPINA3 impairs cartilage formation and reduces levels of SOX9, a master regulator of chondrogenesis, indicating that SERPINA3 is essential for proper chondrocyte differentiation through the regulation of SOX9.
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Purpose: The use of laparoscopy for paediatric inguinal hernia repairs has increased significantly over the past 2 decades. However, there is significant variation in the reported recurrence rates in the literature, with many studies reporting higher rates than the open operation. This may be explained by the range of different techniques currently included under the term laparoscopic inguinal hernia repair.

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Richard Gordon (1921-2017) was a prolific writer of both humorous fiction and historical reviews. He trained in medicine at St Bartholomew's Hospital (Barts) in London and specialised in anaesthesia working at Hill End Hospital, St Albans (where a large proportion of Barts work took place to avoid the impact of the Blitz during the Second World War) and at the Radcliffe Infirmary, Oxford with Robert Macintosh. He published multiple papers and a book on trichlorethylene anaesthesia and edited a textbook of anaesthesia for medical students which ran for 10 editions.

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Introduction:  Opinion remains divided on whether to resect an asymptomatic congenital lung malformation (CLM) and on optimal timing of resection. This study aimed to determine if age at resection of CLM correlates with the presence of histological inflammation and/or incidence of prior antibiotic administration for lower respiratory tract infection (LRTI).

Materials And Methods:  A retrospective review of all CLMs resected between 2009 and 2021 was carried out.

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Victor Goldman specialised in dental anaesthesia from an early age. He published his research all over the world and demonstrated how safety could be improved and how important monitoring of the anaesthetised patient should be. He made films, wrote books, created courses, and invented a myriad of apparatus to improve the speciality and to show trainees how dental anaesthesia should be performed.

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Purpose: Children requiring long-term ventilation (LTV) via tracheostomy often require enteral tube feeding. We sought to investigate what proportion of these children underwent gastrostomy insertion to inform decision making at time of tracheostomy formation.

Methods: A retrospective review of all children commenced on LTV via a tracheostomy at Royal Manchester Children's Hospital over a 9-year period (2012-2020).

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Background: Recent evidence suggests simple laparoscopic inguinal herniorrhaphy is associated with higher rates of recurrence and testicular ascent. We instigated a standardised approach to laparoscopic inguinal herniotomy (LIH), with circumferential sac division and 'purse-string' closure (4/0 monofilament polypropylene). An active follow-up programme was pursued.

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Purpose: Congenital oesophageal stenosis (COS) is characterised by an intrinsic oesophageal narrowing that is present, but not necessarily symptomatic at birth. Small studies report an association of COS with oesophageal atresia (OA) in up to 14% of OA cases. Although OA is usually appreciated shortly after birth, the diagnosis of a concomitant COS is frequently delayed.

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Matrix metalloproteinase-13 (MMP-13) is a uniquely important collagenase that promotes the irreversible destruction of cartilage collagen in osteoarthritis (OA). Collagenase activation is a key control point for cartilage breakdown to occur, yet our understanding of the proteinases involved in this process is limited. Neutrophil elastase (NE) is a well-described proteoglycan-degrading enzyme which is historically associated with inflammatory arthritis, but more recent evidence suggests a potential role in OA.

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Background: Gastrostomy insertion is a common procedure for paediatric surgeons, with the percutaneous endoscopic gastrostomy (PEG) technique long favoured for its simplicity and speed. However, there is growing evidence to suggest that primary laparoscopic balloon gastrostomy (LBG) insertions may have lower complication rates. This study aimed to determine the relative safety and healthcare resource burden of PEG and LBG.

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The administration of chloroform by John Snow to Queen Victoria to provide analgesia for the delivery of her children was a pivotal moment in the development of anaesthesia. It has long been thought that this was the only occasion she had experienced anaesthesia but examination of her diaries shows this to be untrue.

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The collagenase subfamily of matrix metalloproteinases (MMPs) have important roles in the remodeling of collagenous matrices. The proteinase-activated receptor (PAR) family has a unique mechanism of activation requiring proteolysis of an extracellular domain forming a neo-N terminus that acts as a tethered ligand, a process that has been associated with the development of arthritis. Canonical PAR2 activation typically occurs via a serine proteinase at Arg-Ser, but other proteinases can cleave PARs downstream of the tethered ligand and "disarm" the receptor.

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Metalloproteinases remain important players in arthritic disease, in part because members of this large enzymatic family, namely matrix metalloproteinase-1 (MMP-1) and MMP-13, are responsible for the irreversible degradation of articular cartilage collagen. Although direct inhibition of MMPs fell out of vogue with the initial clinical disappointment of the first generation of compounds, interest in other mechanisms that control these important enzymes has always been maintained. Since these enzymes are critically important for tissue homeostasis, their expression and activity are tightly regulated at many levels, not just by direct inhibition by their endogenous inhibitors the tissue inhibitors of metalloproteinases (TIMPs).

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Dr. Richard Gill published a textbook in London in 1906 titled The CHCl - Problem. Gill was the Chief Chloroformist at St Bartholomew's Hospital, London, and was recognized as an excellent clinical anesthetist and was of an intelligent but reclusive and eccentric personality.

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Introduction: Circumcision has long been the mainstay of management for genitourinary lichen sclerosus et atrophicus (LS); however, there has been growing interest in surgical techniques that preserve the foreskin.

Objective: The aim of this study was to assess population-based surgical management of LS in England and determine surgical outcomes.

Study Design: Cases of LS treated in English NHS trusts (2002-2011) were extracted from the Hospital Episode Statistics (HES) Database.

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Irreversible cartilage collagen breakdown by the collagenolytic matrix metalloproteinases (MMPs)-1 and MMP-13 represents a key event in pathologies associated with tissue destruction such as arthritis. Inflammation is closely associated with such pathology and occurs in both rheumatoid and osteoarthritis making it highly relevant to the prevailing tissue damage that characterises these diseases. The inflammation-induced activating protein-1 (AP-1) transcription factor is an important regulator of both MMP1 and MMP13 genes with interplay between signalling pathways contributing to their expression.

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Many catabolic stimuli, including interleukin-1 (IL-1) in combination with oncostatin M (OSM), promote cartilage breakdown via the induction of collagen-degrading collagenases such as matrix metalloproteinase 1 (MMP1) and MMP13 in human articular chondrocytes. Indeed, joint diseases with an inflammatory component are characterised by excessive extracellular matrix (ECM) catabolism. Importantly, protein kinase C (PKC) signalling has a primary role in cytokine-induced MMP1/13 expression, and is known to regulate cellular functions associated with pathologies involving ECM remodelling.

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