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Biomedical subjects

Napier M Thomson

Publications and source records attributed to Napier M Thomson.

6 recordsLinked to original sources
PubMed2006

Predictors of decline in renal function after lung transplantation.

BACKGROUND: Survival after lung transplantation has improved, but with the consequence that long-term toxicities of treatment are of growing importance. In particular, renal impairment is common, has many causes, and carries with it increased morbidity and mortality. METHODS: We retrospectively analyzed clinical and laboratory data of 136 patients who underwent lung and heart-lung transplantation at our institution between 1990 and 2004 inclusive. Using multivariate analysis we considered the impact of age, gender, pulmonary diagnosis, transplant type (single lung, double lung, heart-lung), hypertension, diabetes mellitus, cigarette smoking, current immunosuppression, duration of calcineurin inhibitor (CNI) exposure and pre-existing renal impairment on renal function. RESULTS: At transplantation, creatinine clearance (CrCl) for the patient population was 108 +/- 3.28 (mean +/- SEM) ml/min/1.73 m(2). At end of follow-up (6 +/- 0.32 years) there was a significant decline in glomerular filtration rate (GFR) to 56.7 +/- 1.78 ml/min/1.73 m(2) (p < 0.001). Five of 136 patients (3.7%) developed end-stage renal failure (ESRF). On multivariate analysis, factors most strongly associated with this decline included (in order of significance): CrCl at transplantation; pack-years of cigarette smoking; exposure to sirolimus (SLM); CNI exposure; and age at transplantation. The rate of decline in GFR was linked to CrCl and age at the time of transplantation. CONCLUSIONS: This analysis has demonstrated that patients with a lower baseline CrCl, older age at transplantation, and a smoking history are at high risk for rapid loss of renal function after transplantation. To best preserve kidney function, these patients should be targeted for aggressive risk factor modification as well as minimization of CNI exposure wherever possible.

Adolescent↗
PubMed2005

Beyond operational tolerance: effect of ischemic injury on development of chronic damage in renal grafts.

BACKGROUND: The induction of operational tolerance is the holy grail of clinical transplantation. However, in animal models with operational tolerance, long- term grafts still develop chronic damage. The elucidation of the impact of allogenic versus nonallogeneic factors in such a model is important. This study examined the effect of a clinically relevant combination of warm ischemia and cold preservation in the absence of allogeneic response (isografts) and in the context of operational tolerance. METHODS: Dark Agouti (DA) rat kidneys were transplanted into DA recipients (isografts) or Albino Surgery recipients (allografts) tolerized by two transfusions of DA blood, under cover of cyclosporin A. Grafts were subjected to minimal cold preservation or to 30 mins warm ischemia followed by 24 hrs cold preservation. RESULTS: After an initial peak of renal dysfunction, serum creatinine concentration returned to normal in isografts and nonischemic allografts, but remained significantly elevated in ischemic allografts (P<0.0002) throughout 6 months follow-up. Both allograft groups developed proteinuria. At 6 months, ischemic isografts and nonischemic allografts demonstrated very mild tubular atrophy and interstitial fibrosis. Tubulointerstitial injury was significantly more severe in ischemic allografts (P<0.01 vs. nonischemic allografts) and was associated with increased infiltrating monocyte/macrophages and NK cells (P<0.05). Moderate glomerulosclerosis was a feature of both allograft groups (P<0.05). CONCLUSIONS: The modified allogeneic response in operationally tolerant recipients acts in synergy with ischemia/reperfusion injury in the development of chronic damage. Strategies to limit or modify the initial ischemia/reperfusion injury may ameliorate chronic tubulointerstitial damage. Progressive glomerular damage and proteinuria in allografts may require other pharmacological intervention.

Animals↗
PubMed2004

Lessons from the Clinical Support Systems Program: facilitating better practice through leadership and team building.

The increasing array of strategies and models for improving clinical practice and patient outcomes can be confusing for clinicians. The Clinical Support Systems (CSS) model has proved to be effective in local environments because it demystifies the design and implementation of evidence-based practice improvement projects. The CSS model is simple and has a wide scope. It provides a broad framework with minimalist specifications, enabling clinicians to design their own systems of care that cut across fragmented organisational structures. Implementing simple rules can be an effective strategy for change in complex care systems. These rules do not impose solutions on clinicians, but rather, help them to find creative solutions that have meaning for them and are contextually relevant.

Australia↗
PubMed2004

Increased expression of urotensin II and urotensin II receptor in human diabetic nephropathy.

BACKGROUND: Urotensin II (UII) is an 11-amino acid vasoactive peptide, recently identified as the ligand for a novel G protein-coupled receptor, GPR-14 (renamed urotensin receptor [UT]). In addition to its potent vasoconstrictive actions, UII also has trophic and profibrotic effects, leading to its implication in the pathogenesis of heart failure. However, elevated plasma UII levels also were reported in association with renal impairment and diabetes. Accordingly, the present study sought to examine the expression and localization of UII and its receptor in kidney tissue from patients with diabetic nephropathy. METHODS: We quantified UII and UT gene expression in renal biopsy tissue samples from patients with diabetic nephropathy by using quantitative real-time polymerase chain reaction and determined the intrarenal distribution of their peptides by means of immunohistochemistry. RESULTS: In human diabetic tissue, gene expression of UII and UT were increased 45- and almost 2,000-fold in comparison to control nephrectomy tissue, respectively (P < 0.0001). Immunohistochemical studies showed intense UII peptide staining in diabetic tissue localized predominantly to tubular epithelial cells, and fluorescein-labeled ligand binding studies showed a similar tubular pattern of distribution. CONCLUSION: In the context of its known biological actions, the dramatic overexpression of UII and its receptor implicate this vasoactive peptide as a possible novel factor in the pathogenesis of diabetic nephropathy.

Computer Systems↗
PubMed2003

Over-expression of platelet-derived growth factor in human diabetic nephropathy.

BACKGROUND: The pathogenetic mechanisms responsible for progressive renal impairment of diabetic nephropathy are still poorly understood, despite its growing incidence. Increasing evidence suggests that growth factors may contribute to the initiation and progressive fibrosis of diabetic nephropathy. In this study, the gene expression and protein distribution of platelet-derived growth factor-A and -B (PDGF-A and PDGF-B) in human diabetic nephropathy were examined. METHODS: PDGF-A and PDGF-B mRNA levels in surplus renal biopsy tissue from seven patients with overt diabetic nephropathy and six nephrectomy samples were examined using quantitative reverse transcription-polymerase chain reaction (RT-PCR). In addition, each sample was also examined immunohistochemically to quantify and localize peptide expression of each PDGF isoform. RESULTS: Gene expression of PDGF-A and PDGF-B mRNA were increased 22- and 6-fold, respectively, in biopsies from patients with diabetic nephropathy compared with control tissue. Immunostaining also demonstrated increased peptide expression of both PDGF-A and PDGF-B in diabetic nephropathy, with each isoform showing a specific pattern of tissue distribution. CONCLUSIONS: The findings of increased gene and protein expression of PDGF in renal biopsies from patients with diabetic nephropathy imply a potential role for this prosclerotic growth factor in the development of the progressive fibrosis that characterizes human diabetic kidney disease.

Diabetes Mellitus, Type 2↗