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Background Railroad maintenance of way (MOW) workers are exposed to many workplace hazards, including diesel fuel and exhaust, ballast (silica) dust, asbestos, solvents, herbicides, welding fumes, heavy rolling equipment, vibration and extreme weather. Aims Due to the number of excess deaths we found in a companion standardized mortality ratio (SMR) study for union members <65 years, we hypothesized that these workers may have elevated mortality risks among all ages for many chronic conditions. Methods Proportionate mortality ratios (PMRs) were calculated for 37 661 male MOW workers ages 20 and older who were members of the Brotherhood of Maintenance of Way Employes Division (BMWED). A data set was submitted to the National Death Index (NDI) to identify decedents and to determine cause of death for workers who died between 1979 and 2014. The CDC WONDER database was used to determine expected mortality for US males. Results For certain diseases and cancers the SMR and PMR findings have parallel mortality excesses. Examples include septicaemia and anaemia; diabetes; chronic obstructive pulmonary disease (COPD); nephritis; and transportation accidents. Among cancers, we found excess oesophageal, stomach, colorectal, lung, prostate, kidney and in situ cancers. Two excess SMR findings were not replicated in the PMR assessment—Alzheimer's and Parkinson's disease. Conclusions The PMR findings suggest that some of the mortality excesses from the SMR study are elevated, which adds support to their being consistently raised among BMWED members. The shared excess causes of death in the PMR and SMR studies should be focused on for future prevention and surveillance activities. [ABSTRACT FROM AUTHOR]

Overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in the pathophysiology of heart failure (HF) and chronic kidney disease (CKD). RAAS antagonists can significantly improve clinical outcomes, but monotherapy blocks but one step of the RAAS and can be bypassed through compensatory mechanisms. Providing more complete RAAS blockade by deploying drugs with complementary actions seemed logical - hence the practice of using dual (or triple) RAAS inhibitors. However, RAAS antagonists also exhibit dose-limiting side effects, including acute kidney injury, hyperkalaemia and hypotension, which blunt their overall effectiveness. Despite achieving better RAAS blockade, several trials failed to show clinical outcome improvements. Patients with concomitant CKD and HF (cardiorenal syndrome) are at the greatest risk of these adverse events and therefore the least able to benefit, yet they also have the worst prognosis. This paradox, where those most in need have fewest therapeutic options, poses three questions which are the focus of this review: whether (i) novel therapies that prevent adverse effects can restore therapeutic benefits to patients who would otherwise be RAAS-therapy intolerant, (ii) there are any validated alternatives to their use and (iii) newer approaches to the detection of fluid congestion are ready for implementation. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension is a well-known though poorly characterized disease in veterinary medicine. In humans, pulmonary veno-occlusive disease (PVOD) is a rare cause of severe pulmonary hypertension with a mean survival time of 2 years without lung transplantation. Eleven adult dogs (5 males, 6 females; median age 10.5 years, representing various breeds) were examined following the development of severe respiratory signs. Lungs of affected animals were evaluated morphologically and with immunohistochemistry for alpha smooth muscle actin, desmin, CD31, CD3, CD20, and CD204. All dogs had pulmonary lesions consistent with PVOD, consisting of occlusive remodeling of small- to medium-sized pulmonary veins, foci of pulmonary capillary hemangiomatosis (PCH), and accumulation of hemosiderophages; 6 of 11 dogs had substantial pulmonary arterial medial and intimal thickening. Ultrastructural examination and immunohistochemistry showed that smooth muscle cells contributed to the venous occlusion. Increased expression of CD31 was evident in regions of PCH indicating increased numbers of endothelial cells in these foci. Spindle cells strongly expressing alpha smooth muscle actin and desmin co-localized with foci of PCH; similar cells were present but less intensely labeled elsewhere in non-PCH alveoli. B cells and macrophages, detected by immunohistochemistry, were not co-localized with the venous lesions of canine PVOD; small numbers of CD3-positive T cells were occasionally in and around the wall of remodeled veins. These findings indicate a condition in dogs with clinically severe respiratory disease and pathologic features resembling human PVOD, including foci of pulmonary venous remodeling and PCH. [ABSTRACT FROM AUTHOR]

The consensus management of diabetic nephropathy (DN) in 2015 involves good control of glycaemia, dyslipidaemia and blood pressure (BP). Blockade of the renin-angiotensin-aldosterone system using angiotensin-converting enzyme inhibitors, angiotensin-2 receptor blockers or mineralocorticoid inhibitors are key therapeutic approaches, shown to be beneficial once overt nephropathy is manifest, as either, or both, of albuminuria and loss of glomerular filtration rate. Some significant additional clinical benefits in slowing the progression of DN was reported from the Remission clinic experience, where simultaneous intensive control of BP, tight glycaemic control, weight loss, exercise and smoking cessation were prioritised in the management of DN. This has not proved possible to translate to more conventional clinical settings. This review briefly looks over the history and limitations of current therapy from landmark papers and expert reviews, and following an extensive PubMed search identifies the most promising clinical biomarkers (both established and proposed). Many challenges need to be addressed urgently as in order to obtain novel therapies in the clinic; we also need to examine what we mean by remission, stability and progression of DN in the modern era. [ABSTRACT FROM AUTHOR]

Background: Vascular calcification (VC) is common and is both a marker and a cause of increased cardiovascular morbidity and mortality, especially so in chronic kidney disease (CKD) patients. Renal transplantation is the cornerstone of the successful long-term management of CKD, and in order to satisfy transplantation needs, more use is made now of living kidney donors (LKD). Prior to selection for transplantation, much screening of potential LKD takes place, including for cardiovascular issues. It is not known; however, how much these potentially healthy LKD may be prone to clinically silent VC. Methods: We identified 103 living kidney donors from 2011 renal transplant records. Abdominal aortic calcification (AAC) was assessed using existing abdominal CT imaging using multi-channel CT aortograms (used primarily to assess renal vascular anatomy). Using these CT scans, manual calcium scoring was undertaken to calculate total aortic calcium load (AAC severity score). The prevalence, severity and associations of AAC between calcified and non-calcified donors were then compared. Results: A total of 103 donors were identified from records. Ninety three of these had detailed clinical records to complement their CT scans. Fifty of ninety-three donors were male, and the mean age was 45.9 ± 1.8 years. Mean MDRD eGFR was 88.73 ± 2.97 ml/min/1.73 m. 7.14 ± 3.07 % of the aorta in these donors was calcified with a mean AAC severity score of 0.98 ± 0.56. In kidney donors >50 years of age, there was significantly more AAC than in those <50: 2.47 ± 1.56 versus 0.31 ± 0.29, p < 0.001. There was no relationship between the presence or severity of aortic VC and donor GFR, systolic blood pressure, pulse pressure, calcium-phosphate product or smoking. Conclusions: AAC prevalence, patterns and severity in this important donor population have not previously been described in the literature. There was relatively little VC in what would be regarded as a 'healthy' donor population. VC was more common with age, but the other possible risk factors for the presence or severity of VC did not impact on overall AAC scores. VC did not influence vascular stiffness as represented by pulse pressure. Following the evolution of AAC over time in those who have donated a kidney, and lost some global renal function as a consequence, would be of considerable interest. [ABSTRACT FROM AUTHOR]

Background Pain management in adult patients with concomitant substance use disorders ( SUDs) presents a clinical challenge in the absence of objective assessment criteria. Effective pain management is dependent on the clinician's ability to differentiate true pain symptoms from manipulative behaviours. Successful strategies for achieving effective pain control in these patients include implementing a multidisciplinary team approach, use of non-opioid and non-pharmacologic alternatives, and judicious use of opioid analgesics. Objective To describe the implementation of a pharmacist-driven pain management service for patients with concomitant SUDs. Methods In an urban teaching hospital located in Trenton, New Jersey, United States, a clinical pharmacist-led pain management service evolved to provide formal consultation. Standardised assessment and treatment approaches were developed to assure consistency. Multidisciplinary education was provided to the medical staff. Main outcome measure The study describes a variety of patterns associated with the program from its pilot period through the first 6 years of service, including opioid utilisation, volume and source of consultations, and multidisciplinary perceptions regarding the program's impact. Results The establishment of a pharmacist-led pain management consult service successfully addressed patient's needs while modifying drug-seeking behaviours. A significant decrease in opioid usage was noted during the program's pilot period and sustained over time. The program's success has extended the pharmacist's role beyond the program's initial scope to address general pain management needs and to address educational needs of the medical staff. Today, clinical pharmacists are utilised most often for refractory cases for which the most appropriate method of pain management may not be clear. [ABSTRACT FROM AUTHOR]

The article discusses the toxicity of thiopurines, a class of immunosuppressant and antineoplastic drugs developed by biochemist Gertrude Elion and physician George Hitchings. It describes the drug's mechanism of action and its limitations as therapeutic agents. It offers information on the types of thiopurine toxicity and the various reasons for stopping thiopurines such as nausea and myelotoxicity. It also discusses the risk of malignancy.

Chronic kidney disease (CKD) affects around 10-13% of the general population, with only a small proportion in end stage renal disease (ESRD), either on dialysis or awaiting renal transplantation. It is well documented that CKD patients have an extremely high risk of developing cardiovascular disease (CVD) compared with the general population, so much so that in the early stages of CKD patients are more likely to develop CVD than they are to progress to ESRD. Various pathophysiological pathways and explanations have been advanced and suggested to account for this, including endothelial dysfunction, dyslipidaemia, inflammation, left ventricular hypertrophy and cardiac autonomic dysfunction. In this review, we try to understand and further explore the link between CKD and CVD, as well as offering interventional advice where available, while exposing the current lack of RCT-based research and trial evidence in this area. We also suggest pragmatic Interim measures we could take while we wait for definitive RCTs. [ABSTRACT FROM AUTHOR]

Abnormalities of bone metabolism and increased vascular calcification are common in chronic kidney disease (CKD) and important causes of morbidity and mortality. The Wnt signaling pathway may play a role in the bone and vascular disturbances seen in CKD, termed collectively 'CKD-MBD.' The aim of the study was to investigate the possible association of circulating concentrations of the secreted Wnt signaling inhibitors DKK1 and sclerostin with BMD and arterial stiffness in predialysis CKD. Seventy-seven patients (48 M, 29 F), mean age 57 (SD = 14) years with CKD stages 3B ( n = 32) and 4 ( n = 45) were studied. Sclerostin, DKK1, PTH, and 1,25(OH)D were analyzed. BMD was measured at the lumbar spine (LS), femoral neck (FN), total hip (TH), and forearm (FARM). Arterial stiffness index was determined by contour analysis of digital volume pulse (SI). There was a positive correlation between sclerostin and age ( r = 0.47, p < 0.000). Sclerostin was higher in men than women ( p = 0.013). Following correction for age and gender, there was a negative association between GFR and sclerostin ( p = 0.002). We observed a positive association between sclerostin and BMD at the LS ( p = 0.0001), FN ( p = 0.004), and TH ( p = 0.002). In contrast, DKK1 was negatively associated with BMD at the FN ( p = 0.038). A negative association was seen between DKK1 and SI ( p = 0.027). Our data suggest that the Wnt pathway may play a role in CKD-MBD. Prospective studies are required to establish the clinical relevance of sclerostin and DKK1 as serological markers in CKD. [ABSTRACT FROM AUTHOR]

Mammalian target of rapamycin (mTOR) inhibitors (mTORis) constitute a relatively new category of immunosuppressive and antineoplastic drugs. These share a unique mechanism of action that is focused on the inhibition of the mTOR. Their clinical applications have recently expanded significantly to cover a wide spectrum of immune and non-immune-mediated disorders, including, apart from solid organ transplantation, various solid organ and haematological malignancies, rheumatological and auto-immune diseases such as rheumatoid arthritis, systemic lupus erythematosus, fibrotic conditions, e.g. pulmonary and hepatic fibrosis, and even metabolic problems such as diabetes mellitus and obesity. The most challenging and frequent adverse effects of the mTORis are the haematological ones, especially anaemia, leukopenia and thrombocytopenia. A unique characteristic of mTORi-induced anaemia is concurrent marked microcytosis. Recently, mechanisms have been proposed to explain the microcytic appearance of this anaemia; these include globin production defect, erythropoietin resistance, chronic inflammation, dysregulation of cellular iron metabolism and hepcidin-mediated iron homeostasis interference. As the differential diagnosis of microcytic anaemia includes pure iron deficiency, functional iron deficiency and haemoglobinopathies, characterization of the anaemia requires significant investigation, time and costs. Therefore, understanding of the likely interaction between mTORis and patients is valuable in clinical practice. Moreover, this could expand the drugs' therapeutic applications to other disorders, and suggest novel targets for further research. [ABSTRACT FROM AUTHOR]

Summary: We investigated the association between fibroblast growth factor-23 (FGF-23) and (1) the biochemical parameters implicated in chronic kidney disorder (CKD)-bone and mineral disorder (CKD-MBD) and (2) bone mineral density (BMD) in patients with CKD 1-4. C-reactive protein (CRP) and serum phosphate correlated with FGF-23. A significant association was seen between FGF-23 and BMD at the hip. Introduction: Circulating FGF-23 is elevated in CKD, although the primary stimulus remains unclear. Moreover, it is still unknown whether increase in FGF-23 has a biological effect on bone metabolism. The aim of the study was to investigate the association of FGF-23 with (1) the biochemical parameters linked with CKD-bone and mineral disorder (CKD-MBD) and (2) bone mineral density in CKD. Methods: We studied 145 patients (74 M, 71 F) aged (mean [SD]) 53 [14] years with CKD 1-4. Serum calcium, phosphate, parathyroid hormone, FGF-23, 25 (OH) vitamin D, 1, 25 (OH) vitamin D, bone turnover markers, CRP were determined. BMD was measured at the lumbar spine, femoral neck (FN), forearm, and total hip (TH). Multivariate analysis was undertaken to explore the association between (1) the biochemical variables and FGF-23 and (2) FGF-23 and BMD. Results: Elevations in FGF-23 occurred in CKD stage 3 compared to CKD stage 1/2, although no significant differences in serum phosphate were observed. Serum phosphate ( p < 0.001), CRP ( p < 0.001) and diabetes mellitus ( p < 0.05) were associated with FGF-23. BMD Z-score was significantly lower at the TH and FN in CKD 4 ( p < 0.05). A significant association was seen between BMI, FGF-23, bone specific alkaline phosphatase and BMD at the TH ( p < 0.05). Conclusions: The data suggest that FGF-23 may be associated with parameters implicated in the complications of CKD. Longitudinal studies are required for further clinical evaluation. [ABSTRACT FROM AUTHOR]

Background: Biosimilars or follow-on biologics (FoB) are biopharmaceuticals that, unlike small molecule generic products, are copies of larger, much more complex proteins. As such, data generated from one biopharmaceutical cannot be extrapolated to another. Unlike small molecule generics, FoB require a full developmental programme, albeit smaller than for an originator product. This has been recognized by European regulatory authorities and it is becoming clear that accelerated processes for FoB marketing approval are not feasible. Objective: To determine the balance between costs surrounding FoB (including relatively extensive developmental programmes and subsequent price to the market) and the necessity to ensure efficacy and safety. Principal findings: It is important that FoB are sufficiently tested to ensure patient safety is not compromised. Conducting such a development programme followed by sound pharmacovigilance is very challenging and costly. Conclusions: Cost-savings associated with FoB may be limited. [ABSTRACT FROM AUTHOR]

Background: Biosimilars or follow-on biologics (FoB) are biopharmaceuticals that, unlike small molecule generic products, are copies of larger, much more complex proteins. As such, data generated from one biopharmaceutical cannot be extrapolated to another. Unlike small molecule generics, FoB require a full developmental programme, albeit smaller than for an originator product. This has been recognized by European regulatory authorities and it is becoming clear that accelerated processes for FoB marketing approval are not feasible. Objective: To determine the balance between costs surrounding FoB (including relatively extensive developmental programmes and subsequent price to the market) and the necessity to ensure efficacy and safety. Principal findings: It is important that FoB are sufficiently tested to ensure patient safety is not compromised. Conducting such a development programme followed by sound pharmacovigilance is very challenging and costly. Conclusions: Cost-savings associated with FoB may be limited. [ABSTRACT FROM AUTHOR]

The article presents a study which discusses the use of passive integrated transponder (PIT) incorporated with antenna array technology. This equipment is used for assessing freshwater fish habitats and populations, and to track movements of fishes in past specific locations. According to the study, the use of PIT allows continuous remote monitoring of fish behaviour with minimal levels of intrusion and high levels of temporal and spatial resolution. Details on the advantages and disadvantages of this equipment are also considered.

The hypothesis that the introduction of artificial refuges might provide protection for fish and reduce the level of cormorant predation was tested in two, paired-pond, cross-over trials during the winters of 2003 and 2004, using a ‘refuge’ pond and an adjacent equivalently stocked ‘control’ pond. There were 77% fewer cormorant visits to the refuge pond than the control pond, on average. There was also a 67% fall in the mean mass of fish consumed per cormorant visit and 79% less fish mass lost in the refuge pond. The results are discussed in the context of interactions between cormorants and fish and the potential use of the tool in fisheries management. [ABSTRACT FROM AUTHOR]

We recently identified an erythrocyte nucleotide accumulating in end-stage renal disease as 4-pyridone-3-carboxamide ribonucleotide triphosphate (4PYTP), a nucleotide never described previously. Plasma tryptophan concentration has been previously reported to be reduced in patients in chronic renal failure that is in turn associated with elevated precursors of tryptophan metabolism, including l-kynurenine and quinolinic acid, both of which have been implicated in the neurotoxic manifestations of chronic renal failure. Here we compare mean erythrocyte 4PYTP, and plasma tryptophan concentrations, in controls and four patient groups with renal impairment (10 per group) and confirmed a reduction in plasma tryptophan in patients on dialysis that corrected with renal transplantation. We found: An inverse correlation between plasma tryptophan and red cell 4PYTP concentrations (R2=0.44, P<0.001) when all patients were grouped together. Restoration of both tryptophan and 4PYTP concentrations to control values was only achieved following renal transplantation. 4PYTP was absent from erythrocytes in Molybdenum cofactor (MoCF) deficiency implicating aldehyde oxidase/dehydrogenase, a Molybdenum requiring enzyme. High 4PYTP erythrocyte concentrations in adenine or hypoxanthine-phosphoribosyltransferase deficient patients in severe uremia (113 μM and 103 μM), confirmed the lack of involvement of either enzyme in 4PYTP formation. We propose that 4PYTP is formed by a novel route involving the oxidation of the intermediates of NAD turnover from quinolinic acid by aldehyde oxidase. [ABSTRACT FROM AUTHOR]

In January 2006, NCSU Libraries implemented Endeca as a public interface for the online catalog. This indexing tool exposes selected MARC data elements and allows for guided navigation through the bibliographic data of the Libraries collections using a faceted display based on Library of Congress Subject Headings (LCSH) along with item attributes from an underlying ILS. The article discusses the Endeca technology and NCSU Libraries' implementation of the service. The authors also examine the impact of this revolutionary service on serials including an evaluation of how Endeca complies with several serial-specific recommendations of the University of California Bibliographic Report. A brief discussion of future implications of Endeca on serials concludes the article. [ABSTRACT FROM AUTHOR]

Both chronic kidney disease (CKD) and type II diabetes mellitus (DM) are increasing in frequency among Western populations and both are potent risk factors for the development of anaemia. The presence of CKD and diabetes together represent the most important aetiopathogenic combination for the development of anaemia. New evidence has highlighted some of the underlying mechanisms which make diabetic patients more susceptible to dyserythropoiesis, particularly once they have developed concomitant CKD. In addition, recent publications from large-scale epidemiological studies have highlighted the impact of anaemia on diabetic patients. The purpose of this review was to focus on the pathophysiology and impact of anaemia in DM. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: We investigated the relationship between haemoglobin (Hb) and diabetes in patients with renal disease. Subjects, materials and methods: All adult patients with stable chronic kidney disease attending renal or diabetic outpatient clinics in a six-month period were identified. Patients' notes and electronic patient records were used to build a comprehensive biochemical and clinical database. Results were analysed for the predictors of Hb, the severity of anaemia in both groups and the relative impact of diabetes on haemoglobin and anaemia. Results: The study group consisted of 468 patients, of whom 204 had diabetes and 264 did not. At every level of renal function haemoglobin levels were lower by an average of 10 g/l in subjects with diabetes than in those without. Likewise, anaemia was found to occur at an earlier stage of chronic kidney disease (and to be of greater severity) in diabetic patients. Independent predictors of haemoglobin included female sex, diabetes, renal function and serum albumin, with diabetes and renal function being the greatest predictors. Multiple logistic regression showed that patients with diabetes had an odds ratio of 4 for being anaemic. Had we used an estimated GFR of less than 60 ml/min to trigger investigation of anaemia, we would have detected 85% of anaemic patients. Conclusions/interpretation: Anaemia is frequently found in diabetic patients with renal disease, occurs earlier and is more severe than in similar but non-diabetic subjects. In contrast to previous publications, our findings suggest that anaemia is prevalent at the earliest stages of chronic kidney disease. We advocate an estimated GFR threshold of <60 ml/min to trigger investigation for anaemia in diabetic subjects. [ABSTRACT FROM AUTHOR]

Background: Medical Emergency Teams (MET) have been developed to identify, review and manage acutely unwell ward patients. Previous studies have suggested that there may be obstacles to the utilization and activation of the MET. Aims: To determine the effect of a detailed education programme on the rate of utilization of the MET system 3.5 years after its introduction in a University teaching hospital. Methods: Prospective interventional study involving a detailed programme of education, feedback and decision support for nursing and medical staff given before, during and after implementation of a MET system. We measured the number of MET calls per month for both medical and surgical patients for 109 250 consecutive admissions to the acute care campus of Austin Health from August 2000 to June 2004. Results: Overall activation of the MET increased from 25 calls per month to a peak of 79 calls per month over the study period (average increase of one MET call/month). After standardization for monthly admissions, the increase in MET utilization for surgical patients (increase by 1.13 MET/1000 admissions/month) was 4.9-fold greater than for medical patients (increase by 0.23 MET/1000 admissions/month; P < 0.0001). At the peak level of activity (April 2004), the MET was called to review 8.4% of surgical and 2.7% of medical admissions ( P < 0.0001). Conclusions: There was a progressive increase in the utilization of the MET service in the 3.5 years after implementation, with the rate of uptake 4.9 times greater for surgical than for medical patients. Sustained uptake of the MET system is possible, but increased utilization may take several years to develop. Short-term studies testing the efficacy of the MET system are likely to significantly underestimate its effect on reducing adverse events. Intensive care unit resource adjustments will become necessary to meet increased demand. [ABSTRACT FROM AUTHOR]

ObjectiveTo obtain preliminary data regarding the efficacy and long-term safety of leflunomide in patients with refractory polyarticular-course juvenile rheumatoid arthritis (JRA).MethodsTwenty-seven patients were entered into the initial 26-week open-label study of leflunomide therapy; 17 entered the extension phase (maximum 107 weeks). Mean disease duration at study entry was 7.0 years. All patients had >/=5 joints with active arthritis and had received methotrexate for a mean of 36.0 months. Following a loading dose, patients initially received leflunomide at a dosage of 10 mg/1.73 m[2]/day, which could be increased to 20 mg/1.73 m[2]/day (maximum 20 mg/day) beginning at week 8. The primary efficacy outcome was the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement. Last observation carried forward (LOCF) analysis was used, and all patients were entered into an intent-to-treat analysis. Intraarticular corticosteroids (maximum of 2 in the initial 26 weeks) were allowed, but no new disease-modifying antirheumatic drug or change in nonsteroidal antiinflammatory drug was allowed throughout the study.ResultsSeventeen of the 27 patients (63%) completed the initial 26-week study. Fourteen patients (52%) met the ACR Pedi 30 response criteria at week 26. Seventeen patients entered into the extension phase (13 who met response criteria and 4 who failed to meet response criteria but decided to continue). Nine of the 17 patients (53%) who entered the extension phase either completed all 30 months of study or the study ended prior to the month 30 visit. Five patients withdrew because of failure to maintain efficacy, 2 withdrew their consent, and 1 withdrew because of an adverse event. Using LOCF analysis, 65% of patients met ACR Pedi 30 response criteria at 1 year and 2 years (weeks 50 and 106, respectively) and 53% at the end of the study. Good response rates were also seen using ACR Pedi 50 and ACR Pedi 70 criteria (47% and 24% at week 106, respectively).ConclusionIn this open-label study of JRA patients who either failed to respond to, or were intolerant of, methotrexate, the majority met the ACR Pedi 30 response criteria at week 26. The response was durable, since 53% of patients who entered into the extension phase (maximum 30 months) responded at the end of this phase. Our findings support the further study of the role of leflunomide in the treatment of polyarticular-course JRA. [ABSTRACT FROM AUTHOR]

Objective: To test whether hemofiltration using a hemofilter with large pores (super high flux hemofiltration) achieves effective cytokine removal. Design: Ex vivo study. Setting: Laboratory of an intensive care unit in a tertiary hospital. Patients and participants: Five healthy volunteers. Interventions: Blood was spiked with 1 mg of endotoxin and then circulated through a closed hemofiltration circuit with a large pore polyamide super high flux hemofilter (nominal cut-off point: 100 kDa). Hemofiltration was conducted at 1 l/h or 6 l/h of ultrafiltrate flow. Samples were taken from the arterial, venous and ultrafiltration sampling ports. Measurements and results: Sieving coefficients (SC) above 0.6 were achieved for interleukin (IL)-1β, IL-6 and IL-10 and SCs above 0.3 were achieved for IL-8 and TNF-α at 1 l/h. SCs of all cytokines (except IL-1) were reduced when the ultrafiltration rate was increased from 1 l/h to 6 l/h (p<0.01), but cytokine clearances still increased (p<0.01). The highest SC for albumin was 0.1 at 1 l/h and fell to 0.01 at 6 l/h. No adsorption of cytokines and albumin was observed. Conclusion: High volume ultrafiltration using a super high flux filter achieved cytokine clearances comparable to, or greater than, those currently achieved for urea during standard continuous renal replacement therapy. [ABSTRACT FROM AUTHOR]

Abstract Aim Diabetes is now the commonest cause of end-stage renal failure, so there are many diabetic patients receiving dialysis therapy. There are several important ways in which dialysis practice can impinge unfavourably on glucose control. This study focuses on the interaction between maltose-derived metabolites in a new peritoneal dialysis fluid and blood glucose measurements using reagent sticks that depend on the glucose dehydrogenase method. Case report We report the cases of three patients, with insulin-treated diabetes and end-stage renal disease treated with peritoneal dialysis, who experienced symptomatic hypoglycaemia with inaccurate glucose readings on reagent strips when converted to icodextrin. Conclusion Careful teamwork between diabetes and renal physicians and specialist nurses is highly desirable to achieve good glucose control in a group of patients at particular risk of microvascular and macrovascular complications. Diabet. Med. 18, 679–682 (2001). [ABSTRACT FROM AUTHOR]

Reports on the use of angiotensin-converting enzyme (ACE) inhibitors for the treatment of hypertension in the U.S. Benefits of the therapy with an ACE inhibitor; Superiority of ACE inhibitors as antihypertensive agents; Efficacy of the therapy.

Background Pemphigus vulgaris (PV) autoantibodies (PV-IgG) have been found in 40–70% of sera of first-degree relatives of pemphigus patients. Objectives To determine the possible role of PV-IgG subclasses in the pathogenesis of the disease. Patients and methods Study groups comprised 25 PV patients, 55 unaffected family members and 56 sera of healthy individuals. Indirect immunofluorescence (IIF) staining and Western immunoblotting (WB) techniques were used to determine total PV-IgG and PV-IgG subclasses and their reactivity to desmoglein (Dsg) 1 and 3. Results By IIF staining, circulating PV-IgG were found in 64% of the patients, in 15% of the relatives and in none of the controls (P ≤ 0·001); by WB the results were 91%, 49% and 12%, respectively (P ≤ 0·001). The distribution of PV-IgG subclasses 1–3 was similar among patients and their relatives. PV-IgG4 was found in 62% of the patients but in only one relative and was absent in the controls (P ≤ 0·001). PV-IgG1, 2 and 4 were found to react mainly with Dsg3 and PV-IgG3 mainly with Dsg1 and 3. Conclusions These results support the concept of a genetic predisposition in pemphigus. The non-complement-fixing PV-IgG4 and at least one complement-fixing PV-IgG subclass appear to be involved in the pathogenesis of the disease. The absence of PV-IgG4 among relatives who were PV-IgG carriers seems to be linked to the fact that they do not develop pemphigus. The exact nature of this linkage is still unclear. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ambulatory blood pressure recordings have been shown to correlate better with target organ damage than have isolated clinic blood pressure readings. There have been some small studies demonstrating that abnormal blood pressure diurnal rhythm is common in uraemia and in patients on renal replacement therapy. Abnormal blood pressure diurnal rhythm itself may be a risk factor for accelerated target organ damage. METHODS: We retrospectively studied 480 ambulatory blood pressure recordings in 380 patients with essential hypertension, secondary hypertension, and on renal replacement therapy. We examined diurnal blood pressure rhythm in each group. RESULTS: Abnormal blood pressure diurnal rhythm (non-dipping) is significantly more prevalent in patients with underlying renal disease, even with normal excretory renal function (53%) than in age-, sex-, and race-matched controls with essential hypertension ((30%), P < 0.01). In patients with renal disease the prevalence of non-dipping rose with worsening renal function, reaching statistical significance once plasma creatinine was greater than 400 mumol/l. There was a direct correlation between plasma creatinine and percent decline in blood pressure at night for both systolic (r = 0.23) and diastolic (r = 0.24) blood pressure in patients with underlying renal disease and impaired excretory renal function. High prevalences of abnormal diurnal BP rhythm are seen in patients on haemodialysis (82%), peritoneal dialysis (78%), patients with plasma creatinine > 600 mumol/l (75%), and in renal transplant recipients (74%). CONCLUSIONS: Abnormal blood pressure diurnal rhythm ('non-dipping') is significantly more common in secondary than in primary hypertension, even with normal renal function. Abnormal blood pressure diurnal rhythm becomes increasingly common with advancing uraemia. Once the plasma creatinine is greater than 600 mumol/l the prevalence of non-dipping is the same as that seen with renal replacement therapy. This phenomenon is not modulated by successful renal transplantation. [ABSTRACT FROM PUBLISHER]

Based on correlation analysis with 24-h dialysis collections the peritoneal equilibration test (PET) has been promoted as an aid to prescribe and monitor dialysis dose. However correlation is an incorrect statistical technique to demonstrate the similarity of one measure to another. The closeness (or limits) of agreement should be measured using the technique of Bland and Altman. One hundred and nineteen patients underwent a 24-h dialysate collection and a PET. D/P ratios for urea and creatinine, dialysate volume, urea and creatinine clearance and KT/V (urea) were calculated using both methods and compared using correlation analysis. In addition the limits of agreement, reflecting the potential margins of difference between the two methods, were determined. When used to calculate a daily dialysate volume required to achieve adequacy targets, the PET was found to result in a prescription error range of −0.6 to +1.5 l/day for creatinine clearance and −0.9 to +0.6 l/day for urea clearance. The tendency of the PET to exaggerate clearance resulted in 14% of patients incorrectly achieving a target creatinine clearance of 50 l/week and 17% incorrectly reaching a target KT/V of 1.7. The PET cannot be used in place of 24-h dialysis collections to prescribe or monitor dialysis therapy. [ABSTRACT FROM PUBLISHER]