Search PubMed⌕ Search

Biomedical subjects

David W Johnson

Publications and source records attributed to David W Johnson.

100 records · Page 6Linked to original sources
PubMed2002

Interacting roles of myofibroblasts, apoptosis and fibrogenic growth factors in the pathogenesis of renal tubulo-interstitial fibrosis.

The interrelationship between myofibroblasts and fibrogenic growth factors in the pathogenesis of renal fibrosis is poorly defined. A temporal and spatial analysis of myofibroblasts, their proliferation and death, and presence of transforming growth factor-beta1 (TGF-beta1) and platelet-derived growth factor-B (PDGF-B) was carried out in an established rodent model in which chronic renal scarring and fibrosis occurs after healed renal papillary necrosis (RPN), similar to that seen with analgesic nephropathy. Treated and control groups (N = 6 and 4, respectively) were compared at 2, 4, 8 and 12 weeks. A positive relationship was found between presence of tubulo-interstitial myofibroblasts and development of fibrosis. Apoptotic myofibroblasts were identified in the interstitium and their incidence peaked 2 weeks after treatment. Levels of interstitial cell apoptosis and fibrosis were negatively correlated over time (r = -0.57, p < 0.01), suggesting that as apoptosis progressively failed to limit myofibroblast numbers, fibrosis increased. In comparison with the diminishing apoptosis in the interstitium, the tubular epithelium had progressively increasing levels of apoptosis over time, indicative of developing atrophy of nephrons. TGF-beta1 protein expression had a close spatial and temporal association with fibrosis and myofibroblasts, whilst PDGF-B appeared to have a closer link with populations of other chronic inflammatory cells such as infiltrating lymphocytes. Peritubular myofibroblasts were often seen near apoptotic cells in the tubular epithelium, suggestive of a paracrine toxic effect of factor/s secreted by the myofibroblasts. In vitro, TGF-beta1 was found to be toxic to renal tubular epithelial cells. These findings suggest an interaction between myofibroblasts, their deletion by apoptosis, and the presence of the fibrogenic growth factor TGF-beta1 in renal fibrosis, whereby apoptotic deletion of myofibroblasts could act as a controlling factor in progression of fibrosis.

Animals↗
PubMed2002

Differences in admission rates of children with bronchiolitis by pediatric and general emergency departments.

OBJECTIVE: It is uncertain whether pediatric and general emergency departments have different admitting practices regarding children with bronchiolitis. The objective of this study was to quantify the differences in admission practices between pediatric and general emergency departments of children with bronchiolitis in 1 North American metropolitan area, controlling for various factors such as clinical severity, comorbid conditions, and socioeconomic status. DESIGN: Retrospective cohort review of emergency department visits from April 1992 to March 1997. SETTING: Five emergency departments (1 pediatric and 4 general) serving the Calgary Health Region, which encompasses approximately 850 000 people. PATIENTS: All children residing within the region who visited a regional emergency department and were diagnosed to have bronchiolitis (International Classification of Diseases, Ninth Revision code 466.1, primary or secondary diagnosis). MAIN OUTCOME MEASURE: Population-standardized estimates of admission rates. RESULTS: The medical charts of 3091 children diagnosed to have bronchiolitis during the study period were reviewed. Of this number, 2496 children were evaluated at the pediatric emergency department, and 629 (25%) were admitted. The remaining 595 (19%) were evaluated at the general emergency departments, and 221 (37%) were admitted. Controlling for age, gender, estimated family income based on postal code, medical comorbidity, and clinical severity estimated by presenting respiratory rate and room air oxygen saturation, population-standardized estimates for admission rates at the pediatric and general emergency departments were 24% (standard error: 1%) and 43% (standard error: 2%), respectively. CONCLUSION: Children diagnosed to have bronchiolitis at the Calgary Health Region's pediatric emergency department were about half as likely to be admitted to the hospital as children diagnosed at the region's general emergency departments.

Alberta↗
PubMed2002

Glandular-haired alfalfa resistance to potato leafhopper (Homoptera: Cicadellidae) and hopperburn: development of resistance indices.

Eight proprietary genotypes of glandular-haired alfalfa, Medicago sativa L., supplied by two different companies, were compared for the degree and types of resistance to the potato leafhopper, Ernpoasca fabae (Harris), and hopperburn. A tube cage no-choice bioassay was developed to test leafhopper mortality, feeding, settling preferences, severity of hopperburn symptoms (in this case, defined as both yellowing and stem growth reduction), and trichome density and type on feeding sites. Leafhopper mortality was both strongly and significantly associated with feeding and leaf trichome density; decreased hopperburn symptom severity was weakly, although significantly, associated with increased mortality. To quantify hopperburn in terms of both yellowing and stem growth reduction, we developed a ranking system that reduces overall hopperburn expression to a single number that considers the varying responses to both types of symptoms. Great variability in leafhopper settling, leafhopper mortality, and stem glandular trichome density was detected among alfalfa genotypes, suggesting that genotypic differences may be based on the concentration and/or chemical constituency of the trichome exudates. We postulate that, among variably resistant genotypes of glandular-haired alfalfa, differences among leafhopper responses and hopperburn severity are linked to forced movement from the stems to the leaves as refuge feeding sites. Principal component analysis was performed to reduce the 10 variables down to five biologically significant factors. Scores for these factors were then used to develop resistance indices for potato leafhopper resistance, hopperburn resistance, and an overall glandular-haired alfalfa resistance index.

Animals↗
PubMedDate not supplied

Viral croup: a current perspective.

Viral croup is the most common cause of upper airway obstruction in children 6 months to 6 years of age. Parainfluenza virus accounts for the majority of cases. The disease is characterized by varying degrees of inspiratory stridor, barking cough, and hoarseness because of laryngeal and/or tracheal obstruction. The diagnosis is mainly a clinical one and diagnostic studies usually are not necessary. The management has altered dramatically in the past decade. Good evidence exists to support the routine use of corticosteroid in all children with croup. Intervention at an earlier phase of the illness will reduce the severity of the symptoms and the rates of return to a health care practitioner for additional medical attention, visits to the emergency department, and admission to the hospital. Most children respond to a single, oral dose of dexamethasone. For those who do not tolerate the oral preparation, nebulized budesonide or intramuscular dexamethasone are reasonable alternatives. Nebulized epinephrine should be reserved for patients with moderate to severe croup. Simultaneous administration of corticosteroid and epinephrine reduces the rate of intubation in patients with severe croup and impending respiratory failure.

Administration, Inhalation↗
PubMedDate not supplied

Predictors of decline of residual renal function in new peritoneal dialysis patients.

OBJECTIVE: The aim of this study was to prospectively evaluate the risk factors for decline of residual renal function (RRF) in an incident peritoneal dialysis (PD) population. DESIGN: Prospective observational study of an incident PD cohort at a single center. SETTING: Tertiary-care institutional dialysis center. PARTICIPANTS: The study included 146 consecutive patients commencing PD at the Princess Alexandra Hospital between 1 August 1995 and 1 July 2001 (mean age 54.8 +/- 1.4 years, 42% male, 34% diabetic). Patients with failed renal transplants (n = 26) were excluded. MAIN MEASUREMENTS: Timed urine collections (n = 642) were performed initially and at 6-month intervals thereafter to measure RRF. The development of anuria was also prospectively recorded. RESULTS: The mean (+/- SD) follow-up period was 20.5 +/- 14.8 months. The median slope of RRF decline was -0.05 mL/minute/month/1.73 m2. Using binary logistic regression, it was shown that the 50% of patients with more rapid RRF loss (< -0.05 mL/min/month/1.73 m2) were more likely to have had a higher initial RRF at commencement of PD [adjusted odds ratio (AOR) 1.83, 95% confidence interval (CI) 1.39-2.40] and a higher baseline dialysate/ plasma creatinine ratio at 4 hours (D/P creat; AOR 44.6, 95% CI 1.05-1900). On multivariate Cox proportional hazards model analysis, time from commencement of PD to development of anuria was independently predicted by baseline RRF [adjusted hazard ratio (HR) 0.81, 95% CI 0.60-0.81], D/P creat (HR 2.87, 95% CI 2.06-82.3), body surface area (HR 6.23, 95% CI 1.53-25.5), dietary protein intake (HR 2.87, 95% CI 1.06-7.78), and diabetes mellitus (HR 1.65, 95% CI 1.00-2.72). Decline of RRF was independent of age, gender, dialysis modality, urgency of initiation of dialysis, smoking, vascular disease, blood pressure, medications (including angiotensin-converting enzyme inhibitors), duration of follow-up, and peritonitis rate. CONCLUSIONS: The results of this study suggest that high baseline RRF and high D/P creat ratio are risk factors for rapid loss of RRF. Moreover, a shorter time to the onset of anuria is independently predicted by low baseline RRF, increased body surface area, high dietary protein intake, and diabetes mellitus. Such at-risk patients should be closely monitored for early signs of inadequate dialysis.

Anuria↗
PubMedDate not supplied

The Initiating Dialysis Early and Late (IDEAL) study: study rationale and design.

OBJECTIVES: The primary objective of the IDEAL study is to determine whether the timing of dialysis initiation has an effect on survival in subjects with end-stage renal disease (ESRD). The secondary objectives are to determine the impact of "early start" versus "late start" dialysis on nutritional and cardiac morbidity, quality of life, and economic cost. DESIGN: Prospective multicenter randomized controlled trial. Patients are randomized to commence dialysis at a glomerular filtration rate (by Cockcroft-Gault) of either 10-14 mL/minute/1.73 m2 ("early start") or 5-7 mL/min/1.73 m2 ("late start"), with stratification for dialysis modality (hemodialysis vs peritoneal dialysis), study center, and the presence or not of diabetes mellitus. SETTING: Dialysis units throughout Australia and New Zealand. PATIENTS: Patients with ESRD commencing chronic dialysis therapy. OUTCOME MEASURES: Three years from randomization, all-cause mortality, morbidity, and economic impact; structural and functional cardiac status, nutritional state, and quality of life will be assessed. RESULTS: To date, 388 patients of a minimum 800 patients have been entered and randomized into the study. Current recruitment rates suggest sufficient patients will be enrolled by December 2004 and follow-up completed by December 2007. CONCLUSIONS: The IDEAL study will provide evidence for the optimal time to commence dialysis.

Health Care Costs↗
PubMedDate not supplied

Obesity is a risk factor for peritonitis in the Australian and New Zealand peritoneal dialysis patient populations.

OBJECTIVE: The aim of the present investigation was to examine the association between body mass index (BMI) and peritonitis rates among incident peritoneal dialysis (PD) patients in a large cohort with long-term follow-up. DESIGN: Retrospective observational cohort study of the Australian and New Zealand PD patient population. SETTING: Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. PARTICIPANTS: The study included all incident adult patients (n = 10 709) who received PD in Australia and New Zealand in the 12-year period between 1 April 1991 and 31 March 2003. Patients were classified as obese (BMI > or = 30 kg/m2), overweight (BMI 25.0 - 29.9 kg/m2), normal weight (20 - 24.9 kg/m2), or underweight (< 20 kg/m2). MAIN MEASUREMENTS: Time to first peritonitis and episodes of peritonitis per patient-year were recorded over the 12-year period. RESULTS: Higher BMI was associated with a shorter time to first peritonitis episode, independent of other risk factors [hazard ratio 1.08 for each 5-kg/m2 increase in BMI, 95% confidence interval (CI) 1.04 - 1.12, p < 0.001]. When peritonitis outcomes were analyzed as episodes of peritonitis per patient-year, these rates were significantly higher among patients with higher BMI: underweight 0.69 episodes/year (95% CI 0.66 - 0.73), normal weight 0.79 (95% CI 0.77 - 0.81), overweight 0.88 (95% CI 0.85 - 0.90), obese 1.06 (95% CI 1.02 - 1.09). Coronary artery disease and chronic lung disease were associated with both shorter time to first peritonitis and higher peritonitis rates, independently of these other factors. There was also a "vintage effect," with lower peritonitis rates seen among people who commenced dialysis in more recent years. CONCLUSIONS: Higher BMI at the commencement of renal replacement therapy is a significant risk factor for peritonitis. The mechanisms for this remain undefined.

Adolescent↗
PubMedDate not supplied

A comparison of peritoneal equilibration tests performed 1 and 4 weeks after PD commencement.

OBJECTIVE: The aim of this study was to prospectively evaluate the ability of a peritoneal equilibration test (PET) performed in the first week of peritoneal dialysis (PD) to predict subsequent transport status, as determined by a PET at 4 weeks and >1 year after PD commencement. DESIGN: Prospective observational study of an incident PD cohort at a single center. SETTING: Tertiary-care institutional dialysis center. PARTICIPANTS: The study included 50 consecutive patients commencing PD at the Princess Alexandra Hospital between 25/2/2001 and 14/5/2003 (mean age 60.9 +/- 12.2 years, 54% male, 92% Caucasian, 38% diabetic). All patients were initially prescribed continuous ambulatory PD. MAIN MEASUREMENTS: Measurements performed during paired PETs included dialysate-to-plasma ratios of urea (D/P urea) and creatinine (D/P creatinine) at 4 hours, the ratio of dialysate glucose concentrations at 0 and 4 hours (D/D0 glucose), and drain volumes at 4 hours. RESULTS: When paired 1-week and 1-month PET data were analyzed, significant changes were observed in measured D/P urea (0.91 +/- 0.07 vs 0.94 +/- 0.07 respectively; p < 0.05), D/P creatinine (0.55 +/- 0.12 vs 0.66 +/- 0.11, p < 0.001), and D/D0 glucose (0.38 +/- 0.08 vs 0.36 +/- 0.10, p < 0.05). Using Bland-Altman analysis, the repeatability coefficients were 0.17, 0.20, and 0.13, respectively. Agreement between 1-week and 1-month PET measurements with respect to peritoneal transport category was moderate for D/D0 glucose (weighted kappa 0.52), but poor for D/P urea (0.30), D/P creatinine (0.35), and drain volumes (0.20). The PET measurements performed more than 1 year following PD commencement (n = 28) generally agreed closely with 1-month measurements, and poorly with 1-week measurements. CONCLUSIONS: Peritoneal transport characteristics change significantly within the first month of PD. PETs carried out during this time should be considered preliminary and should be confirmed by a PET 4 weeks later. Nevertheless, performing an early D/D0 glucose measurement at 1 week predicted ultimate transport status sufficiently well to facilitate early clinical decision-making about optimal PD modality while patients were still receiving PD training. On the other hand, the widespread practice of using measured drain volumes in the first week to predict ultimate transport category is highly inaccurate and not recommended.

Female↗