ABSTRACT
Numerous techniques are in use to provide analgesia for labor, of which central neuraxial block is widely considered superior to non-neuraxial options. Central neuraxial techniques have evolved over many years to provide greater efficacy, safety and maternal satisfaction. This narrative review focuses on the literature relating to central neuraxial labor analgesia from the past 5 years, from November 2010 to October 2015. We discuss the evidence related to the various central neuraxial techniques used, the increasingly widespread use of ultrasound guidance and the evidence surrounding other novel methods of central neuraxial block insertion. The timing of institution of central neuraxial analgesia in labor is considered, as are the advances in maintenance regimens for labor analgesia.
Subject(s)
Analgesia, Epidural/methods , Analgesia, Obstetrical/methods , Labor Pain , Pain Management/methods , Catheters , Female , Humans , Pregnancy , Treatment OutcomeABSTRACT
Laparoscopic and minimally-invasive robotic access has transformed the delivery of urological surgery. While associated with numerous desirable outcomes including shorter post-operative stay and faster return to preoperative function, these techniques have also been associated with increased morbidity such as reduced renal blood flow and post-operative renal dysfunction. The mechanisms leading to these renal effects complex and multifactorial, and have not been fully elucidated. However they are likely to include direct effects from raised intra-abdominal pressure, and indirect effects secondary to carbon dioxide absorption, neuroendocrine factors and tissue damage from oxidative stress. This review summarises these factors, and highlights the need for further work in this area, to direct novel therapies and guide alterations in technique with the aim of reducing renal dysfunction post-laparoscopic and robotic surgery.
ABSTRACT
The alpha v beta 6 integrin is a promising target for cancer therapy. Its expression is up-regulated de novo on many types of carcinoma where it may activate transforming growth factor-beta1 and transforming growth factor-beta 3, interact with the specific extracellular matrix proteins and promote migration and invasion of tumor cells. The viral protein 1 (VP1) coat protein of the O(1) British field strain serotype of foot-and-mouth disease virus is a high-affinity ligand for alpha v beta 6, and we recently reported that a peptide derived from VP1 exhibited alpha v beta 6-specific binding in vitro and in vivo. We hypothesized that this peptide could confer binding specificity of an antibody to alpha v beta 6. A 17-mer peptide of VP1 was inserted into the complementarity-determining region H3 loop of MFE-23, a murine single-chain Fv (scFv) antibody reactive with carcinoembryonic antigen (CEA). The resultant scFv (B6-1) bound to alpha v beta 6 but retained residual reactivity with CEA. This was eliminated by point mutation (Y100bP) in the variable heavy-chain domain to create an scFv (B6-2) that was as structurally stable as MFE-23 and reacted specifically with alpha v beta 6 but not with alpha 5 beta 1, alpha v beta 3, alpha v beta 5, alpha v beta 8 or CEA. B6-2 was internalized into alpha v beta 6-expressing cells and inhibited alpha v beta 6-dependent migration of carcinoma cells. B6-2 was subsequently humanized. The humanized form (B6-3) was obtained as a non-covalent dimer from secretion in Pichia pastoris (115 mg/l) and was a potent inhibitor of alpha v beta 6-mediated cell adhesion. Thus, we have used a rational stepwise approach to create a humanized scFv with therapeutic potential to block alpha v beta 6-mediated cancer cell invasion or to deliver and internalize toxins specifically to alpha v beta 6-expressing tumors.