ABSTRACT
We have employed a biological chemistry approach to dissect the mechanisms underpinning cellular responses to oxidant stress and to develop biologically relevant anti-oxidants. We have used telomere biology to define cellular stress responses and have observed telomere independent, p21- and p16-dependent stasis following oxidative insult in human fibroblasts. This was accompanied by a [corrected] reduction in XRCC5 expression and a reduction in [corrected] SIRT 1 expression. Using these markers in conjunction with senescence-associated beta-galactosidase expression, we have developed and screened novel nitrone based anti-oxidant compounds. We have identified functional compounds that are unsuitable for use in primary human cells. This has allowed subsequent identification of suitably structured compounds that act as superior biological anti-oxidants, which have potential for use in clinical interventions.
Subject(s)
Antioxidants/pharmacology , Drug Design , Nitrogen Oxides/chemistry , Telomere/drug effects , Antioxidants/chemistry , Bromodeoxyuridine/metabolism , Cells, Cultured , Cellular Senescence , Cyclin-Dependent Kinase Inhibitor p16/genetics , Cyclin-Dependent Kinase Inhibitor p21/genetics , DNA Helicases/genetics , Dose-Response Relationship, Drug , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/metabolism , Gene Expression/drug effects , Humans , Hydrogen Peroxide/pharmacology , Infant, Newborn , Ku Autoantigen , Molecular Structure , Oxidants/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Structure-Activity Relationship , Telomere/genetics , Telomere/metabolism , beta-Galactosidase/metabolismABSTRACT
There has been speculation as to how the outcome of revision total knee arthroplasty (TKA) compares with that of primary TKA. We have collected data prospectively from patients operated on by one surgeon using one prosthesis in each group. One hundred patients underwent primary TKA and 60 revision TKA. They completed SF-12 and WOMAC questionnaires before and at six and 12 months after operation. The improvements in the SF-12 physical scores and WOMAC pain, stiffness and function scores in both primary and revision TKA patients were highly statistically significant at six months. There was no statistically significant difference in the size of the improvement in the SF-12 physical and WOMAC pain, stiffness and function scores between the primary and revision patients at six months after surgery. The SF-12 mental scores of patients in both groups showed no statistically significant difference after surgery at the six- and 12-month assessments. Our findings show that primary and revision TKA lead to a comparable improvement in patient-perceived outcomes of physical variables in both generic and disease-specific health measures at follow-up at one year.
Subject(s)
Arthritis, Rheumatoid/surgery , Arthroplasty, Replacement, Knee , Osteoarthritis, Knee/surgery , Aged , Aged, 80 and over , Analysis of Variance , Female , Health Status , Humans , Knee Prosthesis , Male , Middle Aged , Prospective Studies , Reoperation , Surveys and Questionnaires , Treatment OutcomeSubject(s)
Foreign-Body Migration/complications , Knee Injuries/etiology , Menisci, Tibial/surgery , Orthopedic Fixation Devices/adverse effects , Postoperative Complications , Tibial Meniscus Injuries , Adult , Foreign-Body Migration/diagnosis , Humans , Knee Injuries/diagnosis , Male , Menisci, Tibial/diagnostic imaging , UltrasonographyABSTRACT
Five cases of perforated diverticular disease are described in which pain in the thigh or leg was the predominant symptom. In four patients pyrexia or leucocytosis were present and three patients ultimately developed surgical emphysema in the left thigh. In retroperitoneal perforation of the colon, the symptoms in the leg may overshadow those in the abdomen and lead to delay in diagnosis.
Subject(s)
Diverticulum, Colon/physiopathology , Intestinal Perforation/physiopathology , Leg , Pain/etiology , Aged , Diverticulum, Colon/diagnostic imaging , Female , Humans , Intestinal Perforation/diagnostic imaging , Middle Aged , RadiographyABSTRACT
A prospective randomised trial (534 patients, 1969-75) was designed to determine whether radical mastectomy conferred advantages over modified radical mastectomy for breast cancer in terms of total survival, local recurrence, distant metastasis, and disease-free interval. The results showed no significant difference in outcome as regards these variables between the two treatments.
