Plasma Levels of Middle Molecules to Estimate Residual Kidney Function in Haemodialysis without Urine Collection

© 2015 Vilar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/Licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.BACKGROUND: Residual Kidney Function (RKF) is associated with survival benefits in haemodialysis (HD) but is difficult to measure without urine collection. Middle molecules such as Cystatin C and β2-microglobulin accumulate in renal disease and plasma levels have been used to estimate kidney function early in this condition. We investigated their use to estimate RKF in patients on HD. DESIGN: Cystatin C, β2-microglobulin, urea and creatinine levels were studied in patients on incremental high-flux HD or hemodiafiltration(HDF). Over sequential HD sessions, blood was sampled pre- and post-session 1 and pre-session 2, for estimation of these parameters. Urine was collected during the whole interdialytic interval, for estimation of residual GFR (GFRResidual = mean of urea and creatinine clearance). The relationships of plasma Cystatin C and β2-microglobulin levels to GFRResidual and urea clearance were determined. RESULTS: Of the 341 patients studied, 64% had urine output>100 ml/day, 32.6% were on high-flux HD and 67.4% on HDF. Parameters most closely correlated with GFRResidual were 1/β2-micoglobulin (r2 0.67) and 1/Cystatin C (r2 0.50). Both these relationships were weaker at low GFRResidual. The best regression model for GFRResidual, explaining 67% of the variation, was: GFRResidual = 160.3 · (1/β2m) - 4.2. Where β2m is the pre-dialysis β2 microglobulin concentration (mg/L). This model was validated in a separate cohort of 50 patients using Bland-Altman analysis. Areas under the curve in Receiver Operating Characteristic analysis aimed at identifying subjects with urea clearance≥2 ml/min/1.73 m2 was 0.91 for β2-microglobulin and 0.86 for Cystatin C. A plasma β2-microglobulin cut-off of ≤19.2 mg/L allowed identification of patients with urea clearance ≥2 ml/min/1.73 m2 with 90% specificity and 65% sensitivity. CONCLUSION: Plasma pre-dialysis β2-microglobulin levels can provide estimates of RKF which may have clinical utility and appear superior to cystatin C. Use of cut-off levels to identify patients with RKF may provide a simple way to individualise dialysis dose based on RKF.Peer reviewe

Physiological Stress and Refuge Behavior by African Elephants

Physiological stress responses allow individuals to adapt to changes in their status or surroundings, but chronic exposure to stressors could have detrimental effects. Increased stress hormone secretion leads to short-term escape behavior; however, no studies have assessed the potential of longer-term escape behavior, when individuals are in a chronic physiological state. Such refuge behavior is likely to take two forms, where an individual or population restricts its space use patterns spatially (spatial refuge hypothesis), or alters its use of space temporally (temporal refuge hypothesis). We tested the spatial and temporal refuge hypotheses by comparing space use patterns among three African elephant populations maintaining different fecal glucocorticoid metabolite (FGM) concentrations. In support of the spatial refuge hypothesis, the elephant population that maintained elevated FGM concentrations (iSimangaliso) used 20% less of its reserve than did an elephant population with lower FGM concentrations (Pilanesberg) in a reserve of similar size, and 43% less than elephants in the smaller Phinda reserve. We found mixed support for the temporal refuge hypothesis; home range sizes in the iSimangaliso population did not differ by day compared to nighttime, but elephants used areas within their home ranges differently between day and night. Elephants in all three reserves generally selected forest and woodland habitats over grasslands, but elephants in iSimangaliso selected exotic forest plantations over native habitat types. Our findings suggest that chronic stress is associated with restricted space use and altered habitat preferences that resemble a facultative refuge behavioral response. Elephants can maintain elevated FGM levels for ≥6 years following translocation, during which they exhibit refuge behavior that is likely a result of human disturbance and habitat conditions. Wildlife managers planning to translocate animals, or to initiate other management activities that could result in chronic stress responses, should consider the potential for, and consequences of, refuge behavior

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

An atypical presentation of myositis ossificans

In the following case study an atypical presentation of myositis ossificans (MO) in the superior anterolateral thigh of a young  soccer player is discussed. This case  demonstrates that MO can present without obvious history of trauma, which makes the diagnosis of this condition more challenging. The most important differential diagnosis is malignant osteosarcoma or soft-tissue sarcoma, which usually presents without trauma. Additionally both pathologies typically occur in the same population.Keywords: case report, ossification, osteosarcom

Osteoid osteoma of the fibula in a female rugby player

Osteoid osteomas are benign osteoblastic tumours encountered relatively commonly among skeletal lesions. Despite distinct clinical findings, atypical presentations make for a challenging or delayed diagnosis which may negatively affect a patient’s quality of life in the interim. We present the case of a young female rugby player with a subperiosteal osteoid osteoma of the distal fibula – a rare location for this type of tumour

Frozen shoulder or missed posterior dislocation?

The clinical presentation of a missed posterior shoulder dislocation has similarities with an idiopathic frozen shoulder masking proper diagnosis at the time of injury. We report a case of a 48-year-old woman with shoulder pain which demonstrates the importance of correct initial diagnosis and management

The effect of simulated gastrointestinal conditions on the antimicrobial activity and chemical composition of indigenous South African plant extracts

Abstract Few in vitro screening assays for biological activities of plant extracts consider the potential effect of the gastrointestinal system on orally consumed plant extracts. Crude water and methanol extracts of Tarchonanthus camphoratus (wild camphor) and Agathosma betulina (‘buchu’) were prepared and exposed to simulated gastric fluid and simulated intestinal fluid during dissolution studies to address this aspect. The crude extracts and resulting simulated gastric fluid and simulated intestinal fluid products were screened for antimicrobial activity against Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 25922) and Proteus vulgaris (ATCC 33420). The T. camphoratus crude extract exhibited antimicrobial activity which was reduced after exposure to simulated gastric fluid. After exposure to simulated intestinal fluid no antimicrobial activity was detected, which suggests chemical alteration or degradation of the active compounds. For A. betulina, the crude water extract and simulated gastric fluid product exhibited no antimicrobial activity, while the simulated intestinal fluid product exhibited antimicrobial activity. This suggests activation of antimicrobial constituents during exposure to simulated intestinal fluid. The chemical composition profiles of the crude extracts and products were determined by means of liquid chromatography coupled to an ultraviolet detector (LC-UV) and a mass spectrometer (LC-MS) to qualitatively assess the effect of exposure to simulated gastrointestinal conditions on the chemical composition of the extracts. In many cases, the peak area of compounds decreased after exposure to simulated gastric fluid and simulated intestinal fluid, while the peak area of other compounds increased. Thus, it can be deduced that the antimicrobial activity and chemical composition was altered after exposure to intestinal conditions during dissolution studies