Michelle J Connolly

Publications (3)7.07 Total impact

• Article: Time to internal fixation of femoral neck fractures in patients under sixty years-does this matter in the development of osteonecrosis of femoral head?

  Fathima Razik, Anastasia-Stefania Alexopoulos, Bassel El-Osta, Michelle J Connolly, Ashley Brown, Soueid Hassan, Kasetti Ravikumar
  [show abstract] [hide abstract]
  ABSTRACT: Osteonecrosis of femoral head remains a major complication of femoral neck fractures. It has been postulated that early internal fixation drastically reduces the incidence of osteonecrosis of the femoral head. However, there is a paucity of literature looking at the effect of time delay to internal fixation on the development of this late complication. In this study, we aim to assess the effect of time delay and method of internal fixation on the development of osteonecrosis in those less than 60 years of age. We retrospectively analysed 92 patients less than 60 years of age who presented with intracapsular neck of femur fractures that underwent internal fixation between 1999 and 2009. Of the 92 intracapsular fractures, 50 underwent fixation using cannulated screws, 32 using a dynamic hip screw, and ten using a dynamic hip screw with a derotation screw. In total, 13 patients (14.1 %) developed osteonecrosis of the femoral head, the highest incidence being in the cannulated screw fixation group with an osteonecrosis rate of 24 %. We did not find the time delay to internal fixation to be a significant predictor of the development of osteonecrosis. Our study demonstrated that the method of internal fixation rather than delay in internal fixation was more predictive of osteonecrosis of the femoral head. We did not find support to the current belief that early surgical fixation of neck of femur fractures reduces the risk of osteonecrosis in patients less than 60 years.
  International Orthopaedics 07/2012; 36(10):2127-32. · 2.03 Impact Factor
• Article: Key role of the RhoA/Rho kinase system in pulmonary hypertension.

  Michelle J Connolly, Philip I Aaronson
  [show abstract] [hide abstract]
  ABSTRACT: Pulmonary hypertension (PH) is a general term comprising a spectrum of pulmonary hypertensive disorders which have in common an elevation of mean pulmonary arterial pressure (mPAP). The prototypical form of the disease, termed pulmonary arterial hypertension (PAH), is a rare but lethal syndrome with a complex aetiology characterised by increased pulmonary vascular resistance (PVR) and progressive elevation of mPAP; patients generally die from heart failure. Current therapies are inadequate and median survival is less than three years. PH due to chronic hypoxia (CH) is a condition separate from PAH and is strongly associated with chronic obstructive pulmonary disease (COPD). An early event in the pathogenesis of this form of PH is hypoxic pulmonary vasoconstriction (HPV), an acute homeostatic process that maintains the ventilation-perfusion ratio during alveolar hypoxia. The mechanisms underlying HPV remain controversial, but RhoA/Rho kinase (ROK)-mediated Ca²+-sensitisation is considered important. Increasing evidence also implicates RhoA/ROK in PASMC proliferation, inflammatory cell recruitment and the regulation of cell motility, all of which are involved in the pulmonary vascular remodelling occurring in all forms of PH. ROK is therefore a potential therapeutic target in treating PH of various aetiologies. Here, we examine current concepts regarding the aetiology of PAH and also PH due to CH, focusing on the contribution that RhoA/ROK-mediated processes may make to their development and on ROK inhibitors as potential therapies.
  Pulmonary Pharmacology &amp Therapeutics 02/2011; 24(1):1-14. · 2.80 Impact Factor
• Article: Cell redox state and hypoxic pulmonary vasoconstriction: recent evidence and possible mechanisms.

  Michelle J Connolly, Philip I Aaronson
  [show abstract] [hide abstract]
  ABSTRACT: During alveolar hypoxia, hypoxic pulmonary vasoconstriction (HPV) maintains blood oxygenation near optimum via incompletely defined mechanisms. It is proposed that a hypoxia-induced rise in the intracellular concentration of reactive oxygen species (ROS) or an oxidising shift in the cytoplasmic redox state provides the signal which initiates the constriction of pulmonary arteries (PA), although this is controversial. Here, we review recent investigations demonstrating that hypoxia causes a rise in [ROS] in PA smooth muscle, and that ROS and antioxidants have effects on PA which would be predicted if cell oxidation causes contraction. We argue that intracellular Ca2+ release and Ca2+-sensitisation are the key effector mechanisms causing HPV, and discuss evidence that both processes are promoted by ROS or oxidative protein modifications. We conclude that while it is plausible that an increase in cytoplasmic [ROS] activates HPV effector mechanisms, proving this link will require the determination of whether hypoxia causes oxidative modifications of proteins involved in Ca2+ homeostasis and sensitisation.
  Respiratory Physiology & Neurobiology 12/2010; 174(3):165-74. · 2.24 Impact Factor