Showing papers by "David W. Johnson published in 2004"

Networks of power and influence: the role of mycorrhizal mycelium in controlling plant communities and agroecosystem functioning

Abstract: Extraradical mycelia of mycorrhizal fungi are normally the �hidden half� of the symbiosis, but they are powerful underground influences upon biogeochemical cycling, the composition of plant communities, and agroecosystem functioning. Mycorrhizal mycelial networks are the most dynamic and functionally diverse components of the symbiosis, and recent estimates suggest they are empowered by receiving as much as 10% or more of the net photosynthate of their host plants. They often constitute 20%�30% of total soil microbial biomass yet are undetected by standard measures of biomass used by soil scientists and agromomists. Mycorrhizal mycelia provide extensive pathways for carbon and nutrient fluxes through soil, often exceeding tens of metres per gram of soil. We consider the amounts of photosynthate �power� allocated to these mycelial networks and how this is used in fungal respiration, biomass, and growth and in influencing soil, plant, and ecosystem processes. The costs and functional �benefits� to plants linking to these networks are fungal specific and, because of variations in physiology and host specificity, are not shared equally; some plants even depend exclusively on these networks for carbon. We briefly assess the potential contribution of extraradical mycorrhizal mycelium to sustainable agriculture and maintenance of biodiversity and highlight technologies that promise new vistas and improved fine-scale resolution of the dynamic spatial and temporal functioning of these networks in soil.Key words: arbuscular mycorrhiza, ectomycorrhiza, extraradical mycelium, hyphal networks.

Plant communities affect arbuscular mycorrhizal fungal diversity and community composition in grassland microcosms

Abstract: Summary • The diversity of arbuscular mycorrhizal (AM) fungi was investigated in an unfertilized limestone grassland soil supporting different synthesized vascular plant assemblages that had developed for 3 yr. • The experimental treatments comprised: bare soil; monocultures of the nonmycotrophic sedge Carex flacca; monocultures of the mycotrophic grass Festuca ovina; and a species-rich mixture of four forbs, four grasses and four sedges. The diversity of AM fungi was analysed in roots of Plantago lanceolata bioassay seedlings using terminal-restriction fragment length polymorphism (T-RFLP). The extent of AM colonization, shoot biomass and nitrogen and phosphorus concentrations were also measured. • The AM diversity was affected significantly by the floristic composition of the microcosms and shoot phosphorus concentration was positively correlated with AM diversity. The diversity of AM fungi in P. lanceolata decreased in the order: bare soil > C. flacca > 12 species > F. ovina. • The unexpectedly high diversity in the bare soil and sedge monoculture likely reflects differences in the modes of colonization and sources of inoculum in these treatments compared with the assemblages containing established AM-compatible plants.

The DNA sequence and comparative analysis of human chromosome 20.

Abstract: Chromosome 5 is one of the largest human chromosomes and contains numerous intrachromosomal duplications, yet it has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding conservation with non-mammalian vertebrates, suggesting that they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-coding genes including the protocadherin and interleukin gene families. We also completely sequenced versions of the large chromosome-5-specific internal duplications. These duplications are very recent evolutionary events and probably have a mechanistic role in human physiological variation, as deletions in these regions are the cause of debilitating disorders including spinal muscular atrophy.

Erythropoietin protects against ischaemic acute renal injury

Abstract: Erythropoietin (EPO) has recently been shown to exert important cytoprotective and anti-apoptotic effects in experimental brain injury and cisplatin-induced nephrotoxicity. The aim of the present study was to determine whether EPO administration is also renoprotectivein both in vitro and in vivo models ofischaemic acute renal failure Methods. Primary cultures of human proximal tubule cells (PTCs) were exposed to either vehicle or EPO (6.25–400 IU/ml) in the presence of hypoxia (1% O2), normoxia (21% O2) or hypoxia followed by normoxia for up to 24 h. The end-points evaluated included cell apoptosis (morphology and in situ end labelling [ISEL], viability [lactate dehydrogenase (LDH release)], cell proliferation [proliferating cell nuclear antigen (PCNA)] and DNA synthesis (thymidine incorporation). The effects of EPO pre-treatment (5000 U/kg) on renal morphology and function were also studied in rat models of unilateral and bilateral ischaemia–reperfusion (IR) injury. Results. In the in vitro model, hypoxia (1% O2) induced a significant degree of PTC apoptosis, which was substantially reduced by co-incubation with EPO at 24 h (vehicle 2.5±0.5% vs 25 IU/ml EPO 1.8±0.4% vs 200 IU/ml EPO 0.9±0.2%, n = 9, P<0.05). At high concentrations (400 IU/ml), EPO also stimulated thymidine incorporation in cells exposed to hypoxia with or without subsequent normoxia. LDH release was not significantly affected. In the unilateral IR model, EPO pre-treatment significantly attenuated outer medullary thick ascending limb (TAL) apoptosis (EPO 2.2±1.0% of cells vs vehicle 6.5±2.2%, P<0.05, n = 5) and potentiated mitosis (EPO 1.1±0.3% vs vehicle 0.5±0.3%, respectively, P<0.05) within 24 h. EPO-treated rats exhibited enhanced PCNA staining within the proximal straight tubule (6.9±0.7% vs vehicle 2.4±0.5% vs sham 0.3±0.2%, P<0.05), proximal convoluted tubule (2.3±0.6% vs vehicle 1.1±0.3% vs sham 1.2±0.3%, P<0.05) and TAL (4.7±0.9% vs vehicle 0.6±0.3% vs sham 0.3±0.2%, P<0.05). The frequency of tubular profiles with luminal cast material was also reduced (32.0±1.6 vs vehicle 37.0±1.3%, P = 0.05). EPO-treated rats subjected to bilateral IR injury exhibited similar histological improvements to the unilateral IR injury model, as well as significantly lower peak plasma creatinine concentrations than their vehicle-treated controls (0.04±0.01 vs 0.21±0.08 mmol/l, respectively, P<0.05). EPO had no effect on renal function in sham-operated controls. Conclusions. The results suggest that, in addition to its well-known erythropoietic effects, EPO inhibits apoptotic cell death, enhances tubular epithelial regeneration and promotes renal functional recovery in hypoxic or ischaemic acute renal injury.

Oak forest carbon and water simulations: model intercomparisons and evaluations against independent data

Abstract: Models represent our primary method for integration of small-scale, process- level phenomena into a comprehensive description of forest-stand or ecosystem function. They also represent a key method for testing hypotheses about the response of forest ecosystems to multiple changing environmental conditions. This paper describes the eval- uation of 13 stand-level models varying in their spatial, mechanistic, and temporal com- plexity for their ability to capture intra- and interannual components of the water and carbon cycle for an upland, oak-dominated forest of eastern Tennessee. Comparisons between model simulations and observations were conducted for hourly, daily, and annual time steps. Data for the comparisons were obtained from a wide range of methods including: eddy covariance, sapflow, chamber-based soil respiration, biometric estimates of stand-level net primary production and growth, and soil water content by time or frequency domain reflectometry. Response surfaces of carbon and water flux as a function of environmental drivers, and a variety of goodness-of-fit statistics (bias, absolute bias, and model efficiency) were used to judge model performance. A single model did not consistently perform the best at all time steps or for all variables considered. Intermodel comparisons showed good agreement for water cycle fluxes, but considerable disagreement among models for predicted carbon fluxes. The mean of all model outputs, however, was nearly always the best fit to the observations. Not surprisingly, models missing key forest components or processes, such as roots or modeled soil water content, were unable to provide accurate predictions of ecosystem responses to short-term drought phenomenon. Nevertheless, an inability to correctly capture short-term physiolog- ical processes under drought was not necessarily an indicator of poor annual water and carbon budget simulations. This is possible because droughts in the subject ecosystem were of short duration and therefore had a small cumulative impact. Models using hourly time steps and detailed mechanistic processes, and having a realistic spatial representation of the forest ecosystem provided the best predictions of observed data. Predictive ability of all models deteriorated under drought conditions, suggesting that further work is needed to evaluate and improve ecosystem model performance under unusual conditions, such as drought, that are a common focus of environmental change discussions.

Catheter-Related Interventions to Prevent Peritonitis in Peritoneal Dialysis: A Systematic Review of Randomized, Controlled Trials

Abstract: As many as 15 to 50% of end-stage kidney disease patients are on peritoneal dialysis (PD), but peritonitis limits its more widespread use. Several PD catheter-related interventions (catheter designs, surgical insertion approaches, and connection methods) have been purported to reduce the risk of peritonitis in PD. The goal was to assess the trial evidence supporting their use. The Cochrane CENTRAL Registry, MEDLINE, EMBASE, and reference lists were searched for randomized trials of catheter types and related interventions in PD. Two reviewers extracted data on the rates of peritonitis and exit-site/tunnel infection, catheter removal/replacement, technique failure, and all-cause mortality. Analysis was by a random effects model, and results are expressed as relative risk and 95% confidence intervals. Thirty-seven eligible trials (2822 patients) were identified: eight of surgical strategies of catheter insertion, eight of straight versus coiled catheters, 10 of Y-set versus conventional spike systems, four of Y-set versus double-bag systems, and seven of other interventions. Despite the large total number of patients, few trials covered the same interventions, small numbers of patients were enrolled in each trial, and the methodologic quality was suboptimal. Y-set and twin-bag systems were superior to conventional spike systems (seven trials, 485 patients; relative risk, 0.64; 95% confidence intervals 0.53 to 0.77), and no other catheter-related intervention was demonstrated to prevent peritonitis in PD. This systematic review demonstrates that of all catheter-related interventions designed to prevent peritonitis in PD, only disconnect (twin-bag and Y-set) systems have been proved to be effective (compared with conventional spike systems). Despite the importance of PD as a renal replacement therapy modality and the large number of patients who receive it, it is still not known whether any particular PD catheter designs, implantation techniques, or modalities are effective, given the limitations of available trials.

A Randomized Trial of a Single Dose of Oral Dexamethasone for Mild Croup

Abstract: background The benefits of dexamethasone treatment for moderate-to-severe croup are well established. However, most children with croup have mild symptoms, and it is unknown whether they would derive the same degree of benefit from dexamethasone treatment as children with more severe disease. methods We conducted a double-blind trial at four pediatric emergency departments in which 720 children with mild croup were randomly assigned to receive one oral dose of either dexamethasone (0.6 mg per kilogram of body weight) or placebo. The children had mild croup, as defined by a score of ≤2 on the croup scoring system of Westley et al. The primary outcome was a return to a medical care provider for croup within seven days after treatment. The secondary outcome was the presence of ongoing symptoms of croup on days 1, 2, and 3 after treatment. Other outcomes included economic costs, hours of sleep lost by the child, and stress on the part of the parent in relation to the child’s illness. results Baseline clinical characteristics were similar in the two groups. Return to medical care was significantly lower in the dexamethasone group (7.3 percent vs. 15.3 percent, P<0.001). In the dexamethasone group, there was quicker resolution of croup symptoms (P=0.003), less lost sleep (P<0.001), and less stress on the part of the parent (P<0.001). conclusions For children with mild croup, dexamethasone is an effective treatment that results in consistent and small but important clinical and economic benefits. Although the longterm effects of this treatment are not known, our data support the use of dexamethasone in most, if not all, children with croup.

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

Abstract: ObjectiveThe 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 w...

Donor treatment with pegylated-G-CSF augments the generation of IL-10 producing regulatory T cells and promotes transplant tolerance

Abstract: We investigated whether the protection from graft-versus-host disease (GVHD) afforded by donor treatment with granulocyte colony-stimulating factor (G-CSF) could be enhanced by dose escalation. Donor treatment with human G-CSF prevented GVHD in the B6 --> B6D2F1 murine model in a dose-dependent fashion, and murine G-CSF provided equivalent protection from GVHD at 10-fold lower doses. Donor pretreatment with a single dose of pegylated G-CSF (peg-G-CSF) prevented GVHD to a significantly greater extent than standard G-CSF (survival, 75% versus 11%, P <.001). Donor T cells from peg-G-CSF-treated donors failed to proliferate to alloantigen and inhibited the responses of control T cells in an interleukin 10 (IL-10)-dependent fashion in vitro. T cells from peg-G-CSF-treated IL-10(-/-) donors induced lethal GVHD; T cells from peg-G-CSF-treated wild-type (wt) donors promoted long-term survival. Whereas T cells from peg-G-CSF wt donors were able to regulate GVHD induced by T cells from control-treated donors, T cells from G-CSF-treated wt donors and peg-G-CSF-treated IL-10(-/-) donors did not prevent mortality. Thus, peg-G-CSF is markedly superior to standard G-CSF for the prevention of GVHD following allogeneic stem cell transplantation (SCT), due to the generation of IL-10-producing regulatory T cells. These data support prospective clinical trials of peg-G-CSF-mobilized allogeneic blood SCT.

Practice variation among pediatric emergency departments in the treatment of bronchiolitis.

Abstract: Objectives: Bronchiolitis is the most common disease of the lower respiratory tract in the first year of life. Treatment is controversial, with studies giving conflicting views on the benefits of bronchodilators and steroids. The objectives of this study were 1) to characterize the management of bronchiolitis in pediatric emergency departments (PEDs) in Canada, 2) to determine patient outcomes following emergency department (ED) visits, and 3) to provide descriptive data regarding bronchiolitis symptoms and family/personal medical history of these patients. Methods: A prospective consecutive cohort of children with bronchiolitis presenting to seven Canadian PEDs was enrolled during a seven-to-21-day period. Standardized interviews with parents provided data regarding symptoms, previous treatment, and past history. Charts were reviewed for treatment, investigations, and disposition. Telephone follow-up at two to three weeks collected information regarding duration of illness and return visits. Results: Two hundred thirty-seven (91%) of 260 eligible patients were enrolled. One hundred eighty-nine patients (80%) had both an interview and chart review, and 48 (20%) had only chart reviews; follow-up was completed for 163 (69%) patients. One hundred fifteen (63%) had seen their primary care provider during their illness prior to the ED visit. Seventythree percent of patients (range per site 59‐100%) were treated in the ED with bronchodilators (usually salbutamol or epinephrine) and 5% (range per site 0‐14%) with oral steroids. Twenty-four percent (58/237) were prescribed bronchodilators on discharge, 3% (7/237) inhaled steroids, and 2% (5/237) oral steroids. Chi-square tests indicated significant practice variation by site in ED bronchodilator use (p \ 0.001) and bronchodilator use at discharge (p = 0.0003). Admission rate was 31% (range by site 22‐ 43%), 17% of patients had more than one ED visit, and 1% were admitted more than once. Admission rates were increased in younger children, children with comorbidities, and children with lower oxygen saturation. Viral studies were obtained in 53%, with 76% of these positive for respiratory syncytial virus (RSV). Median duration of cough was 12 days, poor sleeping and irritability eight days, and wheeze and poor feeding seven days. Conclusions: This study prospectively describes the treatment of bronchiolitis in the pediatric ED. The findings are consistent with the literature regarding the reported use of bronchodilators; however, use of steroids was found to be much lower than reported in other studies. Bronchodilator use in the ED and at discharge varied significantly by site. The results capture variation in treatment practices in Canadian PEDs, which may be the result of discordant randomized controlled trial evidence. Further research is needed to establish best practices. Key words: children; bronchiolitis. ACADEMIC EMERGENCY MEDICINE 2004; 11:353‐360.

Free mycophenolic acid should be monitored in renal transplant recipients with hypoalbuminemia.

Abstract: The current approach for therapeutic drug monitoring in renal transplant recipients receiving mycophenolate mofetil (MMF) is measurement of total mycophenolic acid (MPA) concentration. Because MPA is highly bound, during hypoalbuminemia the total concentration no longer reflects the free (pharmacologically active) concentration. The authors investigated what degree of hypoalbuminemia causes a significant change in protein binding and thus percentage free MPA. Forty-two renal transplant recipients were recruited for the study. Free and total concentrations of MPA (predose, and 1, 3, and 6 hours post-MMF dose samples) and plasma albumin concentrations were determined on day 5 posttransplantation. Six-hour area under the concentration-time curve (AUC(0-6)) values were calculated for free and total MPA, and percentage free MPA was determined for each patient. The authors found a significant relationship between low albumin concentrations and increased percentage free MPA (Spearman correlation = -0.54, P or = 3%) in this patient population was 31 g/L. At this cutoff value albumin was found to be a good predictor of altered free MPA percentage, with a sensitivity and specificity of 0.75 and 0.80, respectively, and an area under the ROC curve of 0.79. To rationalize MMF dosing regimens in hypoalbuminemic patients (plasma albumin < or = 31 g/L), clinicians should consider monitoring the free MPA concentration.

Catheter type, placement and insertion techniques for preventing peritonitis in peritoneal dialysis patients

Abstract: BackgroundAs many as 15-50% of end-stage kidney disease patients are on peritoneal dialysis (PD), but peritonitis limits its more widespread use. Several PD catheter-related interventions have been purported to reduce the risk of peritonitis in PD.ObjectivesTo evaluate the use of catheter-related interventions for the prevention of peritonitis in PD.Search strategyThe Cochrane Renal Group's specialised register (June 2004), The Cochrane CENTRAL Register of Controlled Trials (The Cochrane Library Issue 2 2004), MEDLINE (1966-April 2004), EMBASE (1988-April 2004) and reference lists were searched without language restrictionSelection criteriaTrials comparing different catheter insertion techniques, catheter types, use of immobilisation techniques or different break in periods were included. Trials of different PD sets were excluded.Data collection and analysisTwo reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using a random effects model and the results expressed as risk ratio (RR) with 95% confidence intervals (CI).Main resultsSeventeen eligible trials (1089 patients) were identified, eight of surgical strategies of catheter insertion, eight of straight versus coiled catheters, one of single cuff versus double cuff catheters and one of an immobiliser device. The methodological quality was suboptimal. There were no significant differences with laparoscopy compared with laparotomy for peritonitis, the peritonitis rate, exit-site/tunnel infection or catheter removal/replacement. Standard insertion with resting but no subcutaneous burying of the catheter versus implantation and subcutaneous burying was not associated with a significant reduction in peritonitis rate, exit-site/tunnel infection rate or all-cause mortality. Midline compared to lateral insertion showed no significant difference in the risk of peritonitis or exit-site/tunnel infection. There was no significant difference in the risk of peritonitis, peritonitis rate, exit-site/tunnel infection, exit-site/tunnel infection rate or catheter removal/replacement between straight versus coiled intraperitoneal portion catheters. One trial compared single versus double cuffed catheters and showed no significant difference in the risk of peritonitis, exit-site/tunnel infection or catheter removal/replacement. One trial compared immobilisation versus no immobilisation of the PD catheter and showed no significant difference in the risk of peritonitis and exit-site/tunnel infection. No trials of different break-in periods were identified.Authors' conclusionsNo major advantages from any of the catheter-related interventions which have been purported to reduce the risk of PD peritonitis could be demonstrated in this review. The frequency and quality of available trials are suboptimal.

Medicinal herbal extracts -- renal friend or foe? Part one: the toxicities of medicinal herbs.

Abstract: In recent years, an increasing percentage of people from industrialized countries have been using complementary and alternative medicines (CAM). This, combined with numerous warnings regarding the potential toxicity of these therapies, suggests the need for practitioners to keep abreast of the reported incidence of renal toxicity caused by the ingestion of medicinal herbs. The goal of the present two-part series, on the toxic or beneficial effects of medicinal herbs on renal health, is to provide practitioners with a summary of the most recent information as well as the means by which evidence for benefit or toxicity has been found. In this first article, we explore in vivo evidence of toxicity. Included are nephrotoxicity from aristolochic acid and other components within herbs, herb--drug interactions resulting in adverse renal effects, and renal toxicity from contaminants within the extracts. The review aims to provide a guide to encourage future toxicity studies and rigorous clinical trials.

Fall-related risk factors and osteoporosis in women with rheumatoid arthritis

Abstract: Background. Rheumatoid arthritis (RA) is associated with an increased risk of osteoporotic fractures. Whilst numerous studies have demonstrated low bone density in RA, few studies have examined the risk of falling, which is another major contributor to the pathogenesis of fractures (particularly hip fractures). Objectives. The aim of this study was to see if fall risk is increased in women with RA, define high-risk subgroups, and determine what proportion of women have increased risk of hip fracture due to osteoporosis and due to increased fall risk. Methods. We performed a case–control study of older women with RA (n ¼ 103) compared with women without RA referred for open access bone densitometry (n ¼ 203). We measured bone density using dual-energy X-ray absorptiometry and fall risk factors (visual acuity, ability to perform standups, and heel–toe walking). Results. More women with RA gave a history of a previous fall compared with controls (54 vs 44%), although this was just short of being statistically significant (difference 10%, 95% CI –2 to 22). Women with RA were more likely to have abnormal heel–toe walking and inability to perform standups compared with controls (P<0.001); however, visual acuity was similar between cases and controls. Femoral neck osteoporosis was found in 31% and increased fall risk in 68% of women with RA. Women with RA who underperformed in heel–toe walking and were unable to do standups had significantly higher ESR, Health Assessment Questionnaire score and tender joint count. RA symptoms/signs localized to the knees and ankles were more likely to be associated with the presence of fall risk factors. Conclusions. Fall-related risk factors predictive of hip fracture are common in women with RA. Fall risk needs to be considered when RA patients are being treated for osteoporosis and further work needs to be done to help reduce the risk of falling and fracture in women with RA. Osteoporotic hip fractures are common and cause significant morbidity and mortality. Rheumatoid arthritis (RA) is also a common disease and is associated with doubling of the rate of hip fracture compared with individuals without RA [1–4]. This is in part due to patients with RA having lower bone density at the hip compared with aged-matched non-rheumatoid controls. However, the risk of hip fracture occurring in an individual is determined by both hip bone density and the risk of falling [5, 6]. Although studies have been carried out of hip bone density in RA patients, there are no studies of fall risk and falling. The risk of falls may be higher in RA patients because of lower limb joint disease and muscle weakness (due to disuse and steroids). Visual acuity could also be reduced in steroid-treated patients due to cataract formation. As falls are important in the pathogenesis of hip fractures, this important mechanism of hip fracture may be being overlooked in RA patients. Certainly fear of falling is very common in RA patients, a recent study of 570 patients over the age of 50 yr demonstrating that 50% were concerned about falling [7]. In this study we investigate whether fall risk is increased in women with RA, define high risk subgroups, and determine what proportion of women have increased risk of hip fracture due to osteoporosis and due to increased fall risk. Patients and methods

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

Abstract: 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 m(2) ("early start") or 5-7 mL/min/1.73 m(2) ("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.

Evidence-based guide to slowing the progression of early renal insufficiency.

Abstract: Early renal insufficiency (ERI), defined as a calculated or measured glomerular filtration rate (GFR) between 30 and 60 mL/min per 1.73 m2, is present in more than 10% of the adult Australian population. This pernicious condition is frequently unrecognised, progressive and accompanied by multiple associated comorbidities, including hypertension, renal osteodystrophy, anaemia, sleep apnoea, cardiovascular disease, hyperparathyroidism and malnutrition. Several treatments have been suggested to retard GFR decline in ERI, including blood pressure reduction, angiotensin-converting enzyme inhibition, angiotensin receptor antagonism, calcium channel blockade, cholesterol reduction, smoking cessation, erythropoietin therapy, dietary protein restriction, intensive glycaemic control and early intensive multidisciplinary patient education within a renal unit. In addition, specific interventions have been reported to be renoprotective in atherosclerotic renal artery stenosis, diabetic nephropathy, lupus nephritis and certain forms of primary glomerulonephritis. The present paper reviews the available published randomised controlled clinical trials and meta-analyses supporting (or refuting) a role for each of these therapeutic manoeuvres.

The neurological outcome of non-accidental head injury.

Abstract: Purpose: The literature regarding the outcome of non-accidental head injury (NAHI) is scarce and lacks specific detail even though it is generally considered to be poor The purpose of this study is to review the literature to date and report the neurological outcome of these children in detailMethods: A cross-sectional and prospective study of children admitted to hospital with NAHI in ScotlandResults: Twenty-five children were enrolled and 68% of children were neurologically abnormal at an average follow-up of 59 months A wide range of abnormalities and outcomes was seen Speech and language difficulties were present in 64% including autistic spectrum disorder Cranial nerve abnormalities were present in 20% Visual deficits and epilepsy compounded learning difficulties in 25% of survivors Consent for follow-up was more likely to be obtained where the perpetrator was knownConclusions: The spectrum and degree of severity of neurological abnormalities in survivors of NAHI is extremely variable, with

Cigarette smoking history predicts sensitivity to erlotinib: Results of a phase II trial in patients with bronchioloalveolar carcinoma (BAC)

Abstract: 7062 Background: The most dramatic benefits seen with epidermal growth factor receptor tyrosine kinase inhibitors in patients with NSCLC occur with BAC. For gefitinib, BAC histology and cigarette smoking history predict sensitivity. We now report pretreatment factors associated with radiographic response after erlotinib (Tarceva) in patients with any BAC features (Ebright MI. Ann Thorac Surg 2002) in tumor specimens. Methods: 127 patients with stage IIIB/IV, inoperable NSCLC underwent central review of biopsies. BAC was found in 65%. To date, 69 have received erlotinib 150mg PO daily. Results: Patients: median age 65 (range 33–85 yrs), 64% women, 26% prior chemotherapy, 91% KPS ≥ 80%, Path: 25% "pure" BAC, 74% AdenoCa with BAC features, 29% never smokers. Partial responses occurred in 15 of 59 evaluated, 25% (95% CI 15 to 38%). Response correlated with smoking: 7/19 (37%) in never smokers, 3/7 (43%) in persons smoking ≤ 5 pack yrs and 5/33 (15%) in those smoking ≥ 6 pack yrs. Responses occurred in 1/14 (7...

Implementing the "Teaching Students to be Peacemakers Program"

Abstract: The Teaching Students To Be Peacemakers Program trains every student in a school in the competencies they need to (a) resolve conflicts constructively and (b) make their schools safe places in which to learn. The program is directly based on the theory and research on constructive conflict resolution. More than 16 studies in 2 different countries have been conducted on the program's effectiveness. The evidence indicates that without training, children and adolescents tend to manage their conflicts in destructive ways. When given training, however, they learn how to engage in integrative negotiations and how to mediate their schoolmates' conflicts. They maintain their ability to do so months after the training has ended. They apply the learned procedures to actual conflicts in the classroom, school, and family settings. Learning the negotiation and mediation procedures can be integrated with academic learning in a way that enhances subject matter understanding.

Detailed cost analysis of care for survivors of severe sepsis.

Abstract: ObjectivesThe objectives of our study were to accurately describe the costs and resources required to treat survivors of severe sepsis subsequent to hospital discharge and to determine what factors influenced these costs.DesignObservational cohort study.SettingThree regional intensive care units.Pat

Severe toxicity associated with a markedly elevated mycophenolic acid free fraction in a renal transplant recipient.

Abstract: A 58-year-old man with end-stage renal failure secondary to polycystic kidney disease developed a profoundly elevated mycophenolic acid (MPA) free fraction and associated severe toxicity after cadaveric renal transplantation. Initial immunosuppressive therapy was 4 mg/kg body weight bid cyclosporin (Neoral(R); Novartis Pharmaceutical Co Ltd, Sydney, Australia) given orally with 1 g bid mycophenolate mofetil (MMF) (CellCept(R); Roche Products Ply Ltd, Sydney, Australia). In the first 5 days pottransplantation, the serum creatinine concentration fell, and the patient developed profound hypoalbuminemia (serum albumin 150 mumol/L) that resulted from progressing biliary obstruction. On day 5 posttransplantation, the 2-hour whole-blood cyclosporin concentration and total MPA area under the curve (AUC(0-6)) were low (837 mug/L and 12.6 mg(.)h/L, respectively), while the total mycophenolic acid glucuronide (MPAG) AUC(0-6) was elevated (1317 mgy-h/L). MMF was continued at the same dose, but tacrolimus substituted for cyclosporin. The patient subsequently experienced severe nausea, vomiting, hematemesis, and pancytopenia (nadir white cell count 1.6 x 10(9)/L, platelet count 32 x 10(9)/L, and hemoglobin 73 g/L) that were normalized after cessation of MMF Retrospective measurement of the free MPA concentration on day 5 showed that free MPA AUC(0-6) was markedly elevated at 2.3 mg(.)h/L, as was the free fraction, at 18.3%. This case illustrates how altered protein binding can be associated with severe MMF toxicity caused by an increased free MPA concentration despite relatively low total MPA. These data support the monitoring of free MPA concentrations in those patients considered at risk for MMF-related toxicity.

The effect of oral iron admiinistration on mycophenolate mofetil absorption in renal transplant recipients: a randomized, controlled trial.

Abstract: Background. Oral iron supplements are frequently prescribed to renal transplant recipients in the early posttransplant period. A recent trial in seven healthy volunteers demonstrated a significant 91% reduction in mycophenolate mofetil (MMF) absorption when co-administered with oral iron. However, the effect of iron on MMF absorption in renal transplant patients has not been studied.

Sleep dysfunction in patients with gastro-oesophageal reflux disease: prevalence and response to GERD therapy, a pilot study.

Abstract: Summary Background : There is little information on the prevalence of pathological sleep disorders in patients with gastro-oesophageal reflux disease and whether pharmacological treatment of patients with gastro-oesophageal reflux disease will lead to improvement in sleep. Aims: This pilot study determined the prevalence of sleep disorder in patients with erosive gastro-oesophageal reflux disease, correlated subjective (questionnaire) and objective (actigraphy – a watch worn on the wrist that monitors motion to help differentiate sleep from awake states) assessment of sleep dysfunction and determined whether therapeutic resolution of oesophageal symptoms was associated with an improvement in sleep. Methods : Eighteen patients with erosive gastro-oesophageal reflux disease received esomeprazole 40 mg once daily for 8 weeks. Assessments at 0, 4 and 8 weeks included: Gastrointestinal Symptoms Rating Scale, Pittsburgh Sleep Quality Index questionnaire and ambulatory wrist actigraphy. Results : Unrecognized sleep disturbance occurred in 81% of this cohort of patients with gastro-oesophageal reflux disease and erosive oesophagitis. Median reflux syndrome score (heartburn and acid regurgitation) on Gastrointestinal Symptoms Rating Scale decreased from 2 at baseline to 0 at weeks 4 and 8 (P ≤ 0.0001). Median global Pittsburgh Sleep Quality Index score decreased from 8.50 at baseline to 4.50 at week 4 (P = 0.002) and to 7.00 at week 8 (P = 0.043). There were no significant changes in actigraphy measurements. Conclusions : Sleep disturbance is common in patients with gastro-oesophageal reflux disease with erosive oesophagitis. This study which is the first to evaluate sleep abnormalities and gastro-oesophageal reflux disease using a validated questionnaire, demonstrates that in patients with gastro-oesophageal reflux disease, sleep improvement, may be effected by gastro-oesophageal reflux disease therapy. Actigraphy may be inappropriate for measurement of sleep disturbance in gastro-oesophageal reflux disease patients.

ABX-EGF in combination with paclitaxel and carboplatin for advanced non-small cell lung cancer (NSCLC)

Abstract: 7083 Background: ABX-EGF is a high-affinity, fully human, IgG2 monoclonal antibody directed against epidermal growth factor receptor (EGFr). This is a report of results from part 1 of a 2-part, phase 2 trial to evaluate the efficacy, safety, and pharmacokinetics (PK) of ABX-EGF in combination with paclitaxel and carboplatin for advanced NSCLC. Methods: In this open-label, sequential, dose-escalation design in pts with NSCLC (stage IIIb or IV) and EGFr expression of 2+ or 3+ in >=10% of tumor cells, pts received weekly IV ABX-EGF in combination with standard paclitaxel and carboplatin every 3 weeks for up to 6 cycles; pts with response or stable disease could receive extended ABX-EGF therapy. Responses (RECIST) were evaluated at week 6 with confirmation >=3 weeks later. The PK of ABX-EGF and paclitaxel were evaluated at weeks 0 and 3. Results: Nineteen pts (5 men/14 women; mean [SD] age 52.2 [11.9] years) were enrolled into 3 ABX-EGF cohorts: 1.0 mg/kg (n=6), 2.0 mg/kg (n=7), and 2.5 mg/kg (n=6). One pt (5...