ELISA versus PCR for diagnosis of chronic Chagas disease: systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Most current guidelines recommend two serological tests to diagnose chronic Chagas disease. When serological tests are persistently inconclusive, some guidelines recommend molecular tests. The aim of this investigation was to review chronic Chagas disease diagnosis literature and to summarize results of ELISA and PCR performance.</p> <p>Methods</p> <p>A systematic review was conducted searching remote databases (MEDLINE, LILACS, EMBASE, SCOPUS and ISIWeb) and full texts bibliography for relevant abstracts. In addition, manufacturers of commercial tests were contacted. Original investigations were eligible if they estimated sensitivity and specificity, or reliability -or if their calculation was possible - of ELISA or PCR tests, for chronic Chagas disease.</p> <p>Results</p> <p>Heterogeneity was high within each test (ELISA and PCR) and threshold effect was detected only in a particular subgroup. Reference standard blinding partially explained heterogeneity in ELISA studies, and pooled sensitivity and specificity were 97.7% [96.7%-98.5%] and 96.3% [94.6%-97.6%] respectively. Commercial ELISA with recombinant antigens studied in phase three investigations partially explained heterogeneity, and pooled sensitivity and specificity were 99.3% [97.9%-99.9%] and 97.5% [88.5%-99.5%] respectively. ELISA's reliability was seldom studied but was considered acceptable. PCR heterogeneity was not explained, but a threshold effect was detected in three groups created by using guanidine and boiling the sample before DNA extraction. PCR sensitivity is likely to be between 50% and 90%, while its specificity is close to 100%. PCR reliability was never studied.</p> <p>Conclusions</p> <p>Both conventional and recombinant based ELISA give useful information, however there are commercial tests without technical reports and therefore were not included in this review. Physicians need to have access to technical reports to understand if these serological tests are similar to those included in this review and therefore correctly order and interpret test results. Currently, PCR should not be used in clinical practice for chronic Chagas disease diagnosis and there is no PCR test commercially available for this purpose. Tests limitations and directions for future research are discussed.</p

Personalized therapy for mycophenolate:Consensus report by the international association of therapeutic drug monitoring and clinical toxicology

When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and comprehensive presentation of consensus on the status for personalized treatment with MPA, this report was prepared following an initiative from members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). Topics included are the criteria for analytics, methods to estimate exposure including pharmacometrics, the potential influence of pharmacogenetics, development of biomarkers, and the practical aspects of implementation of target concentration intervention. For selected topics with sufficient evidence, such as the application of limited sampling strategies for MPA area under the curve, graded recommendations on target ranges are presented. To provide a comprehensive review, this report also includes updates on the status of potential biomarkers including those which may be promising but with a low level of evidence. In view of the fact that there are very few new immunosuppressive drugs under development for the transplant field, it is likely that MPA will continue to be prescribed on a large scale in the upcoming years. Discontinuation of therapy due to adverse effects is relatively common, increasing the risk for late rejections, which may contribute to graft loss. Therefore, the continued search for innovative methods to better personalize MPA dosage is warranted.</p

Insulin glargine effect on glycemic control and hypoglycemia risk in patients with type 2 diabetes mellitus and chronic kidney disease stages 3 and 4: a randomized, open-label controlled clinical trial

Diabetes mellitus (DM) é uma das principais causas de doença renal crônica terminal. Na doença renal diabética (DRD) observa-se um curso bifásico no padrão glicêmico, na fase inicial o aumento da resistência insulínica induz a hiperglicemia e, com perda progressiva da taxa de filtração glomerular, há redução na depuração dos medicamentos anti-hiperglicemiantes e insulina, aumentando o risco de hipoglicemias. Portanto, diante da perda da função renal, a reavaliação da terapia hipoglicemiante e ajustes constantes nas doses de insulina são necessários, com intuito de otimizar o controle glicêmico e minimizar seus efeitos colaterais. A revisão da literatura mostra diversos pontos sem resposta, principalmente relacionados à dose, ajuste da terapia insulínica, seguimento e monitoração do controle glicêmico em portadores de DM e DRC. O objetivo deste ensaio randomizado, cruzado, controlado foi comparar o controle glicêmico do tratamento com insulina glargina à insulina NPH em portadores de DM2 e DRD estágios 3 e 4. Pacientes e métodos: Trinta e quatro pacientes foram randomizados para receber insulina glargina uma vez ao dia ou insulina NPH em três aplicações diárias. Insulina lispro foi prescrita três vezes ao dia, em aplicações pré-prandiais nos dois grupos. Após 24 semanas de terapia, os pacientes tiveram seu esquema de insulina trocado para terapia insulínica oposta. Testes laboratoriais foram realizados após 12, 24, 36 e 48 semanas de estudo. O sistema de monitorização continua de glicose (CGMS) foi instalado ao término de cada terapia. Resultados: Dos 34 pacientes incluídos, 29 completaram as 48 semanas propostas no estudo, 2 pacientes perderam seguimento por má adesão e 3 pacientes não completaram o estudo em decorrência a eventos adversos (1 óbito, 1 ingresso em hemodiálise e 1 evento cardiovascular, todos em uso de insulina NPH). Após 24 semanas de tratamento com insulina glargina houve uma redução estatisticamente significante da média da HbA1c de 8,86 ± 1,4% para 7,95 ± 1,1% (p=0,0285), esta diferença não foi observada com a insulina NPH (8,21 ± 1,29% para 8,44 ± 1,32%). Durante o uso de insulina glargina o número de eventos noturnos de hipoglicemia foi menor comparado a insulina NPH (p=0,046); além disso, hipoglicemia grave ocorreu apenas na terapêutica com NPH. Conclusão: O tratamento com insulina glargina foi associado a melhor controle glicêmico e a redução do risco de hipoglicemia noturna quando comparada à insulina NPH,em pacientes portadores de DM e DRC estágios 3 e 4Diabetes mellitus is the leading cause of chronic kidney disease (CKD). Kidney disease diagnosis and its progression require re-evaluation of hypoglycemic therapy and constant dosing adjustments, to optimize glycemic control and minimize its side effects. Long acting insulin analogs and its pharmacokinetics have not been studied in different stages of kidney disease, nor is there consensus defining appropriate dose adjustment in patients with type 2 diabetes (T2DM) and CKD. The aim of this randomized, cross-over, open-label controlled clinical trial is to compare the glycemic response to intensive insulin treatment with NPH insulin or insulin glargine in T2DM patients and CKD stages 3 and 4. The primary efficacy end point was change in A1C from baseline. Thirty-four patients were randomized to receive insulin glargine once a day or NPH insulin, three times a day. Insulin lispro was prescribed as prandial insulin to both groups. After six months, patients switched to the other insulin therapy group. Laboratory tests were performed at baseline at 12, 24, 36 and 48 weeks. A continuous glucose monitoring system was implemented after 24 weeks and at the end of protocol. Results: Total of 29 subjects have completed the two branches of study, 2 patients dropped out due to low compliance and other 3 patients as a result of adverse events (1 death, 1 ingress on dialysis program, 1 cardiovascular event; all of them were on NPH therapy). After 24 weeks, average of A1c decreased on glargine group compared to baseline 8,86 ± 1,4% to 7,95 ± 1,1% (p=0,0285), but this difference was not observed on NPH group. There were no differences of insulin doses between both groups. Glargine group showed a tendency of lower risk of nocturnal hypoglycemia compared to NPH group (p=0,046). Conclusion: Insulin glargine improved glycemic control by reducing HbA1c without gain weight and with reduced tendency toward nocturnal hypoglycemic events compared with NPH insuli

Determination of the temperature distribution of ESP motors under variable conditions of flow rate and loading

A model to predict the motor temperature of an electrical submersible pump (ESP), under variable conditions of flow rate and loading, has been developed. This model takes into account the coupled behavior between motor, pump and production system. Thus, given a defined frequency in the variable speed drive, the motor temperature was determined as a result of the equilibrium between the heat generation, calculated from the power that the pump demands from the motor, and the heat extraction resistance, calculated from the production flow rate around the motor. Furthermore, in real field operations, the measurement of the motor temperature is made at the lower end of the stator winding, which is not exactly the maximum temperature point. In order to predict the maximum motor temperature value, the model developed in this work determines the motor temperature distribution. A convective heat transfer study has also been made comparing models based on fully developed temperature profile to models that consider the development of the thermal boundary layer. A case study has been made with several oil viscosities and water cut. The results showed a fact commonly observed in ESP field operations, that is, the motor temperature rises when the motor speed is continuously increased. It was also shown that neglecting the effect of the thermal boundary layer development may result in an overheated motor prediction where actually, the motor maximum temperature is much lower than its upper limit. Thus, it was observed that fully developed temperature profile models suffer from inaccuracy when used in viscous oil applications, because of their great thermal entry length12911012

T cells activate the tumor necrosis factor-alpha system during hemodialysis, resulting in tachyphylaxis

T cells activate the tumor necrosis factor-α system during hemodialysis, resulting in tachyphylaxis.BackgroundThe immunosuppressive state of hemodialysis (HD) patients is accompanied by activation of antigen-presenting cell-derived cytokines, for example, tumor necrosis factor-α (TNF-α), which are required for T-cell activation. To test whether an activated TNF-α system results in impaired T-cell response in these patients, we analyzed parameters of their antigen-presenting cell (APC) function (for example, TNF-α system) and T-cell function [for example, interleukin-2 (IL-2) system].MethodsBy quantitative flow cytometry, the expression of the TNF-receptor 2 (TNF-R2 = CD120b) and the α and β chain of the IL-2 receptor (IL-2R; CD25, CD122) was measured. Using reverse transcriptase-polymerase chain reaction, the mRNA for TNF-α, IL-2, and IL-2R were determined. Phyto-hemagglutinin (PHA)- and IL-2–stimulated proliferation and cytokine production were measured. Biological activity of soluble receptors was measured by adding recombinant cytokines to the patient's plasma.ResultsCD120b expression was significantly increased in HD patients, whereas CD25 and CD122 was comparable to controls. In contrast to mRNA for IL-2 and IL-2R, mRNA for TNF-α was increased in HD. This resulted in significantly increased TNF-α levels in HD patients. In peripheral blood of HD patients, high levels of soluble TNF-R (R1 and R2) and IL-2R were found. These receptors were capable of binding 40% of added TNF-α and 55% of added IL-2. PHA-induced TNF-α production by T cells from HD patients was significantly lower, while their PHA-stimulated IL-2 production and proliferation capacity by T cells were comparable to controls.ConclusionsWe conclude that although the TNF-α system is activated during HD, the TNF-α production of T cells is impaired, suggesting that tachyphylaxis of T cells occurs for TNF-α, as their proliferative capacity and IL-2 production capacity do not imply an intrinsic T-cell defect

Paulista registry of glomerulonephritis: 5-year data report

Background. The Paulista Registry of Glomerulopathies was created in May 1999 and comprises several centres of Sao Paulo, the most populous Brazilian State, that concentrates people from all regions of the country who look for health care. Methods. This report includes data from 2086 patients from Brazil submitted to renal biopsy due to the presumed diagnosis of glomerular diseases, registered prospectively since May 1999 until January 2005. Data were collected by the integrants of the 11 centres involved, utilizing a standardized questionnaire. Results. The mean age of the patients was 34.5 +/- 14.6 years. Primary glomerular diseases were more frequent in males (55.1%) than in females; on the other hand, secondary glomerular diseases were more frequent in females (71.8%). The most common clinical presentation was nephrotic syndrome and the frequency of hypertension, at this time, was 55.5%. There was a predominance of indication of biopsies in the third, fourth and fifth decades of life. The most common primary glomerular diseases were focal and segmental glomerulosclerosis (29.7%), followed by membranous nephropathy (20.7%), IgA nephropathy (17.8%), minimal change disease (9.1%), membranoproliferative glomerulonephritis (7%), crescentic glomerulonephritis (4.1%), advanced chronic glomerulopathy (4%), non-IgA mesangial glomerulonephritis (3.8%), diffuse proliferative glomerulonephritis (2.5%), focal segmental proliferative glomerulonephritis (1%) and others (0.3%). The most frequent secondary glomerular disease was lupus nephritis, corresponding to 66.2% of the cases, followed by post-infectious glomerulonephritis (12.5%), diabetic nephropathy (6.2%), diseases associated to paraproteinaemia (4.9%), hereditary diseases (4.6%), vasculitis (3.2%), malignancies (0.9.%), secondary focal segmental glomerulosclerosis (0.6%) and others (0.9%). Conclusion. Focal segmental glomerulosclerosis was the most frequent primary glomerular disease, followed by membranous nephropathy and IgA nephropathy. Lupus nephritis predominated over all the other secondary glomerular diseases.21113098310