Publications by authors named "Andrew J Freidin"

5 Publications

  • Page 1 of 1

CT Texture Analysis of Ex Vivo Renal Stones Predicts Ease of Fragmentation with Shockwave Lithotripsy.

J Endourol 2017 07 5;31(7):694-700. Epub 2017 Jun 5.

1 Oxford Stone Group, University of Oxford , Oxford, United Kingdom .

Introduction: Understanding the factors affecting success of extracorporeal shockwave lithotripsy (SWL) would improve informed decision-making on the most appropriate treatment modality for an individual patient. Although stone size and skin-to-stone distance do correlate with fragmentation efficacy, it has been shown that stone composition and architecture, as reflected by structural heterogeneity on CT, are also important factors. This study aims to determine if CT texture analysis (CTTA), a novel, nondestructive, and objective tool that generates statistical metrics reflecting stone heterogeneity, could have utility in predicting likelihood of SWL success.

Materials And Methods: Seven spontaneously passed, intact renal tract stones, were scanned ex vivo using standard CT KUB and micro-CT. The stones were then fragmented in vitro using a clinical lithotripter, after which, chemical composition analysis was performed. CTTA was used to generate a number of metrics that were correlated to the number of shocks needed to fragment the stone.

Results: CTTA metrics reflected stone characteristics and composition, and predicted ease of SWL fragmentation. The strongest correlation with number of shocks required to fragment the stone was mean Hounsfield unit (HU) density (r = 0.806, p = 0.028) and a CTTA metric measuring the entropy of the pixel distribution of the stone image (r = 0.804, p = 0.039). Using multiple linear regression analysis, the best model showed that CTTA metrics of entropy and kurtosis could predict 92% of the outcome of number of shocks needed to fragment the stone. This was superior to using stone volume or density.

Conclusions: CTTA metrics entropy and kurtosis have been shown in this experimental ex vivo setting to strongly predict fragmentation by SWL. This warrants further investigation in a larger clinical study for the contribution of CT textural metrics as a measure of stone heterogeneity, along with other known clinical factors, to predict likelihood of SWL success.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/end.2017.0084DOI Listing
July 2017

G mutation in mice causes hypocalcemia rectifiable by calcilytic therapy.

JCI Insight 2017 02 9;2(3):e91103. Epub 2017 Feb 9.

Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.

Heterozygous germline gain-of-function mutations of G-protein subunit α (Gα), a signaling partner for the calcium-sensing receptor (CaSR), result in autosomal dominant hypocalcemia type 2 (ADH2). ADH2 may cause symptomatic hypocalcemia with low circulating parathyroid hormone (PTH) concentrations. Effective therapies for ADH2 are currently not available, and a mouse model for ADH2 would help in assessment of potential therapies. We hypothesized that a previously reported dark skin mouse mutant () - which has a germline hypermorphic Gα mutation, Ile62Val - may be a model for ADH2 and allow evaluation of calcilytics, which are CaSR negative allosteric modulators, as a targeted therapy for this disorder. Mutant and mice were shown to have hypocalcemia and reduced plasma PTH concentrations, similar to ADH2 patients. In vitro studies showed the mutant Val62 Gα to upregulate CaSR-mediated intracellular calcium and MAPK signaling, consistent with a gain of function. Treatment with NPS-2143, a calcilytic compound, normalized these signaling responses. In vivo, NPS-2143 induced a rapid and marked rise in plasma PTH and calcium concentrations in and mice, which became normocalcemic. Thus, these studies have established mice, which harbor a germline gain-of-function Gα mutation, as a model for ADH2 and have demonstrated calcilytics as a potential targeted therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.91103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291742PMC
February 2017

Night-time immobilization of the distal interphalangeal joint reduces pain and extension deformity in hand osteoarthritis.

Rheumatology (Oxford) 2014 Jun 8;53(6):1142-9. Epub 2014 Feb 8.

Arthritis Research UK Centre for OA Pathogenesis, Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, Rheumatology Department, Therapies Department, Charing Cross Hospital, Imperial College Healthcare NHS Trust, Centre for Haematology, Hammersmith Hospital, Imperial College London, Imaging Department, Charing Cross Hospital, Imperial College Healthcare NHS Trust and Department of Imaging, King's College Hospital, London, UK.Arthritis Research UK Centre for OA Pathogenesis, Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, Rheumatology Department, Therapies Department, Charing Cross Hospital, Imperial College Healthcare NHS Trust, Centre for Haematology, Hammersmith Hospital, Imperial College London, Imaging Department, Charing Cross Hospital, Imperial College Healthcare NHS Trust and Department of Imaging, King's College Hospital, London, UK.

Objective: DIP joint OA is common but has few cost-effective, evidence-based interventions. Pain and deformity [radial or ulnar deviation of the joint or loss of full extension (extension lag)] frequently lead to functional and cosmetic issues. We investigated whether splinting the DIP joint would improve pain, function and deformity.

Methods: A prospective, radiologist-blinded, non-randomized, internally controlled trial of custom splinting of the DIP joint was carried out. Twenty-six subjects with painful, deforming DIP joint hand OA gave written, informed consent. One intervention joint and one control joint were nominated. A custom gutter splint was worn nightly for 3 months on the intervention joint, with clinical and radiological assessment at baseline, 3 and 6 months. Differences in the change were compared by the Wilcoxon signed rank test.

Results: The median average pain at baseline was similar in the intervention (6/10) and control joints (5/10). Average pain (primary outcome measure) and worst pain in the intervention joint were significantly lower at 3 months compared with baseline (P = 0.002, P = 0.02). Differences between intervention and control joint average pain reached significance at 6 months (P = 0.049). Extension lag deformity was significantly improved in intervention joints at 3 months and in splinted joints compared with matched contralateral joints (P = 0.016).

Conclusion: Short-term night-time DIP joint splinting is a safe, simple treatment modality that reduces DIP joint pain and improves extension of the digit, and does not appear to give rise to non-compliance, increased stiffness or joint restriction.

Trial Registration: clinical trials.gov, http://clinicaltrials.gov, NCT01249391.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/ket455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023558PMC
June 2014

Ultrasonographic measures of synovitis in an early phase clinical trial: a double-blind, randomised, placebo and comparator controlled phase IIa trial of GW274150 (a selective inducible nitric oxide synthase inhibitor) in rheumatoid arthritis.

Clin Exp Rheumatol 2012 Mar-Apr;30(2):254-61. Epub 2012 Apr 13.

Kennedy Institute of Rheumatology, London, UK.

Objectives: To test the sensitivity to change of ultrasonographic endpoints in early phase clinical trials in subjects with active rheumatoid arthritis (RA).

Methods: A double-blind, placebo and comparator controlled, randomised, two-centre study investigated the effect on synovial thickness and vascularity of 28 days repeat daily oral dosing of 60 mg of the inducible nitric oxide synthase inhibitor GW274150 or 7.5 mg prednisolone in RA. Fifty patients with DAS28 scores ≥4.0 were assigned to 3 treatment arms of 17, 19 and 14 (on placebo, GW274150 and prednisolone respectively). Synovial thickness and vascularity of all 10 metacarpophalangeal joints were assessed by ultrasonography using a semi-quantitative scale at baseline (Day 1), Day 15 and Day 28. Vascularity was also measured quantitatively by power Doppler area.

Results: At Day 28, the GW274150 group showed a trend towards reduction in synovial thickness compared with placebo, with an adjusted mean decrease of 33% (p=0.072); the prednisolone group decreased significantly by 44% (p=0.011). Similarly, there was a trend to reduced synovial vascularity with GW274150 by 42% compared with placebo (p=0.075); prednisolone resulted in a statistically significant decrease of 55% (p=0.012). There was a 55% decrease in power Doppler area for GW274150, compared with placebo although the result was not statistically significant (p=0.375). Prednisolone 7.5 mg resulted in a highly statistically significant decrease of 95% (p=0.003).

Conclusions: This study advocates the use of ultrasonographic measures of metacarpophalangeal joint synovitis as an endpoint for clinical studies assessing therapeutic potential of new compounds in small patient cohorts over 28 days.
View Article and Find Full Text PDF

Download full-text PDF

Source
July 2012

Effects of extensor synovectomy and excision of the distal ulna in rheumatoid arthritis on long-term function.

J Hand Surg Am 2010 Sep 29;35(9):1442-8. Epub 2010 Jul 29.

Kennedy Institute of Rheumatology, Imperial College, London, United Kingdom.

Purpose: Objective outcomes data after excision of the distal ulna in rheumatoid arthritis are lacking. The aim of this study was to evaluate the functional results of this surgery in the long term.

Methods: We prospectively collected data on range of motion (22 wrists), visual analog pain scores (14 wrists), and grip strength measured using a Jamar dynamometer (20 hands) in a group of 23 patients (26 wrists) preoperatively and at 3 months, 12 months, and a minimum of 5 years postoperatively (range, 5.3-10.4 y). The Jebsen-Taylor hand function test was administered to 9 patients at the same time points. A subgroup of patients also underwent extensor carpi radialis longus to extensor carpi ulnaris tendon transfer (11 wrists).

Results: At one year, there were improvements in wrist pronation and supination, which were maintained at final follow-up. Active radial deviation decreased significantly at 3 months (p = .01) and one year (p = .02); this remained reduced at final follow-up (not significant). Wrist extension and active ulnar deviation showed slight improvements by one year, but reduced to levels below that measured preoperatively by final follow-up. Wrist flexion was significantly reduced at all time points postoperatively. Grip strength showed improvement from 10.0 kg (standard deviation [SD] 4.1 kg) preoperatively to 12.5 kg (SD 4.6 kg) 1 year after surgery and returned to preoperative levels (9.5 kg, SD 5.6 kg) by final follow-up. Wrist pain was significantly reduced from a mean score of 5 (SD 4) preoperatively to 2 (SD 2) postoperatively (p = .01). The Jebsen-Taylor hand function test showed improvements in writing and card turning.

Conclusions: In the long term, excision of the distal ulna in rheumatoid patients results in an improvement in some aspects of hand function. There is a significant (p = .01) reduction in wrist pain but a reduction of wrist flexion.

Type Of Study/level Of Evidence: Therapeutic IV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhsa.2010.04.034DOI Listing
September 2010
-->