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Objective: COVID-19 is associated with an elevated risk of thromboembolism and excess mortality. Difficulties with best anticoagulation practices and their implementation motivated the current analysis of COVID-19 patients who developed Venous Thromboembolism (VTE)., Method: This is a post-hoc analysis of a COVID-19 cohort, described in an economic study already published. The authors analyzed a subset of patients with confirmed VTE. We described the characteristics of the cohort, such as demographics, clinical status, and laboratory results. We tested differences amid two subgroups of patients, those with VTE or not, with the competitive risk Fine and Gray model., Results: Out of 3186 adult patients with COVID-19, 245 (7.7%) were diagnosed with VTE, 174 (5.4%) of them during admission to the hospital. Four (2.3% of these 174) did not receive prophylactic anticoagulation and 19 (11%) discontinued anticoagulation for at least 3 days, resulting in 170 analyzed. During the first week of hospitalization, the laboratory most altered results were C-reactive protein and D-dimer. Patients with VTE were more critical, had a higher mortality rate, worse SOFA score, and, on average, 50% longer hospital stay., Conclusion: Proven VTE incidence in this severe COVID-19 cohort was 7.7%, despite 87% of them complying completely with VTE prophylaxis. The clinician must be aware of the diagnosis of VTE in COVID-19, even in patients receiving proper prophylaxis., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: Coronavirus disease 2019 (COVID-19) is associated with high mortality among hospitalized patients and incurs high costs. Severe acute respiratory syndrome coronavirus 2 infection can trigger both inflammatory and thrombotic processes, and these complications can lead to a poorer prognosis. This study aimed to evaluate the association and temporal trends of D-dimer and C-reactive protein (CRP) levels with the incidence of venous thromboembolism (VTE), hospital mortality, and costs among inpatients with COVID-19., Methods: Data were extracted from electronic patient records and laboratory databases. Crude and adjusted associations for age, sex, number of comorbidities, Sequential Organ Failure Assessment score at admission, and D-dimer or CRP logistic regression models were used to evaluate associations., Results: Between March and June 2020, COVID-19 was documented in 3,254 inpatients. The D-dimer level ≥4,000 ng/mL fibrinogen equivalent unit (FEU) mortality odds ratio (OR) was 4.48 (adjusted OR: 1.97). The CRP level ≥220 mg/dL OR for death was 7.73 (adjusted OR: 3.93). The D-dimer level ≥4,000 ng/mL FEU VTE OR was 3.96 (adjusted OR: 3.26). The CRP level ≥220 mg/dL OR for VTE was 2.71 (adjusted OR: 1.92). All these analyses were statistically significant (p<0.001). Stratified hospital costs demonstrated a dose-response pattern. Adjusted D-dimer and CRP levels were associated with higher mortality and doubled hospital costs. In the first week, elevated D-dimer levels predicted VTE occurrence and systemic inflammatory harm, while CRP was a hospital mortality predictor., Conclusion: D-dimer and CRP levels were associated with higher hospital mortality and a higher incidence of VTE. D-dimer was more strongly associated with VTE, although its discriminative ability was poor, while CRP was a stronger predictor of hospital mortality. Their use outside the usual indications should not be modified and should be discouraged.

Background. Health and social management of the SARS-CoV-2 epidemic, responsible for the COVID-19 disease, requires both screening tools and diagnostic procedures. Reliable screening tests aim at identifying (truely) infectious individuals that can spread the viral infection and therefore are essential for tracing and harnessing the epidemic diffusion. Instead, diagnostic tests should supplement clinical and radiological findings, thus helping in establishing the diagnosis. Several analytical assays, mostly using RT-PCR-based technologies, have become commercially available for healthcare workers and clinical laboratories. However, such tests showed some critical limitations, given that a relevant number of both false-positive and false-negative cases have been so far reported. Moreover, those analytical techniques demonstrated to be significantly influenced by pre-analytical biases, while the sensitivity showed a dramatic time dependency. Aim. Herein, we critically investigate limits and perspectives of currently available RT-PCR techniques, especially when referring to the required performances in providing reliable epidemiological and clinical information. Key Concepts. Current data cast doubt on the use of RT-PCR swabs as a screening procedure for tracing the evolution of the current SARS-COV-2 pandemic. Indeed, the huge number of both false-positive and false-negative results deprives the trustworthiness of decision making based on those data. Therefore, we should refine current available analytical tests to quickly identify individuals able to really transmit the virus, with the aim to control and prevent large outbreaks.

The demand for high value health care uncovered a steady trend in laboratory tests ordering and inappropriate testing practices. Residents' training in laboratory ordering practice provides an opportunity for quality improvement. We collected information on demographics, the main reason for the appointment, preexisting medical conditions and presence of co-morbidities from first-visit patients to the internal medicine outpatient service of our university general hospital. We also collected information on all laboratory tests ordered by the attending medical residents. At a follow-up visit, we recorded residents' subjective perception on the usefulness of each ordered laboratory test for the purposes of diagnosis, prognosis, treatment or screening. We observed that 17.3% of all ordered tests had no perceived utility by the attending resident. Tests were usually ordered to exclude differential diagnoses (26.7%) and to help prognosis estimation (19.1%). Age and co-morbidity influenced the chosen category to legitimate usefulness of tests ordering. This study suggests that clinical objectives (diagnosis, prognosis, treatment or prevention) as well as personalization to age and previous health conditions should be considered before test ordering to allow a more appropriate laboratory tests ordering, but further studies are necessary to examine this framework beyond this medical training scenario., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To evaluate the trend of use of Prostate Specifi c Antigen (PSA) for screening of prostate cancer (PC) among Brazilian doctors, from the beginning of its regular availability in clinical laboratories., Material and Methods: A serial cross-sectional study was performed using data obtained from a large database between 1997 and 2016. The general PSA screening trend during this period, adjusted for the total number of exams performed in men, was analyzed. Time-series analysis was performed through observation of the general regression curve using the generalized least squares method, and the impact of the recommendations was assessed with autoregressive integrated moving average (ARIMA) models., Results: During the period studied 2,521,383 PSA determinations were done. The age of the participants ranged from 21 to 111 years, with an average of 56.7 ± 22.7 years. The relative number of PSA tests/100.000 exams in males showed a constant reduction since 2001, and this trend was more evident in the group aged 55-69 years. Although statistically signifi cant, the impact of reduced PSA screening after the 2012 USPSTF publication was clinically irrelevant., Conclusions: Our results indicated a continuous reduction in the use of PSA screening over time, regardless of the publication of recommendations or clinical guidelines. The fact that this trend was more pronounced among those with a greater benefi t potential (55-69 years), relative to groups with a greater damage potential due to overdiagnosis and overtreatment (aged >74 years and < 40 years), is a matter of concern. Follow-up studies of these trends are advisable., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Aim: To detect differences in the pattern of serum calcium tests ordering before and after the implementation of a decision algorithm., Methods: We studied patients admitted to an internal medicine ward of a university hospital on April 2013 and April 2016. Patients were classified as critical or non-critical on the day when each test was performed. Adequacy of ordering was defined according to adherence to a decision algorithm implemented in 2014., Results: Total and ionised calcium tests per patient-day of hospitalisation significantly decreased after the algorithm implementation; and duplication of tests (total and ionised calcium measured in the same blood sample) was reduced by 49%. Overall adequacy of ionised calcium determinations increased by 23% (P=0.0001) due to the increase in the adequacy of ionised calcium ordering in non-critical conditions., Conclusions: A decision algorithm can be a useful educational tool to improve adequacy of the process of ordering serum calcium tests., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The use of point-of-care testing (POCT) in different clinical applications is justified by the fact that the time to release the result is shortened, allowing the physician to define the diagnosis and most appropriate therapy in a shorter time. However, the negative aspects must also be highlighted and studied so that we can move forward with the use of these devices. These negative aspects include greater analytical imprecision compared to laboratory automation, the variability between different equipment from different manufacturers, the risk of inappropriate use, a low level of global regulation, higher costs compared with laboratory testing and cost ineffectiveness in terms of health care. Methods and., Results: This review presents some clinical applications of POCT in different scenarios, such as for diabetes mellitus, infectious diseases, pediatrics, and chronic kidney disease, among others., Conclusions: We hope to see a global consensus on an acceptable quality standard for performing POCT that is adaptable, practical, and cost effective in primary care settings, ensuring patient safety, and minimizing the risk of harm.

Point-of-Care Testing (POCT) has been highlighted in the health care sector in recent decades. On the other hand, due to its low demand, POCT is at a disadvantage compared to conventional equipment, since its cost is inversely proportional to the volume of use. In addition, for the implementation of POCT to succeed, it is essential to rely on the work of a multidisciplinary team. The awareness of health professionals of the importance of each step is perhaps the critical success factor. The trend towards the continuous advancement of the use of POCT and the great potential of its contributions reinforce the need to implement quality management tools, including performance indicators, to ensure their results. This review presents some advantages and disadvantages concerning POCT and the real need to use it. A worldwide call for the availability of easy-to-use health technologies that are increasingly closer to the final user is one of the main reasons for this focus.

Objectives: The adequacy of laboratory test orders by medical residents is a longstanding issue. The aim of this study is to analyze the number, types, and pattern of repetition of tests ordered by medical residents., Methods: We studied all tests ordered over a 1-year period for inpatients of an internal medicine ward in a university hospital. Types, results, and repetition pattern of tests were analyzed in relation to patients' diagnoses., Results: We evaluated 117,666 tests, requested for 1,024 inpatients. The mean number of tests was 9.5 per day. The test repetition pattern was similar, regardless of patients' diagnoses, previous test results, or duration of stay. The probability of an abnormal result after a sequence of three normal tests was lower than 25%, regardless of the diagnosis., Conclusions: Number of tests and repetition were both high, imposing costs, discomfort, and risks to patients, thus warranting further investigation., (© American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Hepatitis C virus (HCV) infection is often persistent and gradually advances from chronic hepatitis to liver cirrhosis and hepatocellular carcinoma (HCC). Worldwide, hepatocellular carcinoma is the fifth most common neoplasm., Method of Study: the Interferon lambda (IFNL) polymorphisms genotypes (rs8099917, rs12979860 and rs12980275) and the presence of mutations in HCV core protein were analyzed in 59 patients with HCC, and also in 50 cirrhotic patients (without HCC)., Results: the rs12980275-AG genotype was associated with HCC on age-adjusted analysis (OR 2.42, 95% CI 1.03-5.69, P=0.043). Core substitutions R70Q and L91M were mainly found in genotype 1b isolates. Furthermore, a borderline level of statistical significance association was found among the presence of amino acid Glutamine (Q) in the position 70 and IFNL3 genotype AG (P=0.054)., Conclusions: the screening of these polymorphisms and functional studies would be useful in clinical practice for identifying groups at high risk of HCC development., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Nephropathic cystinosis is an autosomal recessive systemic severe disease characterized by intralysosomal cystine storage. Cysteamine is an essential component of treatment. There is solid evidence that cystine accumulation itself is not responsible for all abnormalities in cystinosis; there is also a deficiency of glutathione in the cytosol. Patients with cystinosis can be more susceptible to oxidative stress., Case-Diagnosis/treatment: The patient cohort comprised 23 cystinosis patients (16 males) aged <18 years (mean age 8.0 ± 3.6 years) with chronic kidney disease class I-IV with good adherence to treatment, including cysteamine. Oxidative stress was evaluated based on the levels of serum thiobarbituric acid-reactive substances (TBARS), and renal function was evaluated based on serum creatinine and cystatin C levels and creatinine clearance (Schwartz formula). N-Acetylcysteine (NAC), an antioxidant drug was given to all patients for 3 months (T1) at 25 mg/kg/day divided in three doses per day. The measured values at just before the initiation of NAC treatment (T0) served as the control for each patient., Results: Median serum TBARS levels at T0 and T1 were 6.92 (range 3.3-29.0) and 1.7 (0.6-7.2)  nmol/mL, respectively (p < 0.0001). In terms of renal function at T0 and T1, serum creatinine levels (1.1 ± 0.5 vs. 0.9 ± 0.5 mg/dL, respectively; p < 0.0001), creatinine clearance (69.7 ± 32.2 vs. T1 = 78.5 ± 33.9 mL/min/1.73 m(2), respectively; p = 0.006), and cystatin c level (1.33 ± 0.53 vs. 1.15 ± 0.54 mg/l, respectively; p = 0.0057) were all significantly different at these two time points. Serum creatinine measurements at 6 (T -6) and 3 months (T -3) before NAC initiation and at 3 (T +3) and 6 months (T +6) after NAC had been withdrawn were also evaluated., Conclusion: During the 3-month period that our 23 cystinosis patients were treated with NAC, oxidative stress was reduced and renal function significantly improved. No side-effects were detected. Larger and controlled studies are needed to confirm these findings.

Context and Objective: This study was motivated by the recent excessive increase in requests for blood calcium determinations and laboratory tests in general, in the Hospital das Clínicas complex of Faculdade de Medicina, Universidade de São Paulo (HCFMUSP). Its aim was to suggest rules for the determination of total and ionized calcium in our intensive care units, emergency department, wards and outpatient services, thus contributing towards improving the quality of medical care and achieving more appropriate use of human and financial resources., Design and Setting: Critical analysis on clinical and laboratory data and the pertinent scientific literature, conducted by the study group for rational clinical laboratory use, which is part of the Central Laboratory Division, HCFMUSP., Methods: The study group reviewed scientific publications, statistics and clinical and laboratory data concerning requests for total and ionized calcium determinations in the settings of intensive care units, emergency department, wards and outpatient services., Results: From this critical analysis, clinical decision flow diagrams aimed at providing guidance for ordering these tests were constructed., Conclusions: Use of the proposed flow diagrams may help to limit the numbers of inappropriate requests for ionized and total calcium determinations, with consequent reductions in the number of tests, risks to patients and unnecessary costs.

Recent years have witnessed a substantial increase in the number of seric determinations of vitamin D, in a worldwide basis. At Hospital das Clínicas of Faculdade de Medicina of Universidade de São Paulo that increase reached 700% over the last four years. Nevertheless there are many controversies on the literature about the role of vitamin D in conditions unrelated to the musculoskeletal system. In this study the metabolism, sources and actions of vitamin D on the body are reviewed. Observational studies, clinical trials, systematic reviews and metanalysis which focused on the relationship between the vitamin and conditions such as cancer, cardiovascular disease, diabetes and falls were searched on the literature, analyzed and discussed. Results are presented as quiz and answer, tables and a figure. The role of vitamin D on the above-mentioned conditions is discussed, and the controversial issues stressed., (Copyright © 2013 Elsevier Editora Ltda. All rights reserved.)

C-reactive protein (CRP) is an acute-phase protein whose requests have been growing exponentially in several countries, including Brazil. In this study, the use of CRP in several clinical situations was reviewed by a group of physicians comprised by specialists in internal medicine, medical emergencies, intensive care, screening, and laboratory medicine, aiming to analyze the applicable literature and to propose guidelines for a more rational use of this laboratory test. The result was the creation of flowcharts guiding CRP request, adjusted to four different healthcare environments, namely, intensive care units, emergency room, wards, and outpatient clinics. These flowcharts, as well as a more detailed discussion on several clinical recommendations for the test, are presented in this study.

Background: Cystinosis is an autossomic recessive systemic disease that leads to renal insufficiency early in life unless cysteamine be started early. Unfortunately, even in this situation the patients will develop chronic renal disease with need of renal replacement therapy about second decade of life. Therefore, the renal function evaluation is essential to these patients. The aim of this study was to evaluate cystatin C, serum creatinine and creatinine clearance estimated by stature (Schwartz Formula) in cystinosis patients, with different degrees of renal function, and to correlate these parameters., Methods: We studied cystinosis patients, aged lower than 18 years, with different degrees of renal function, classified according to KDOQI in Chronic Kidney Disease stage 1 to 4. No patient was under renal replacement therapy. In these patients we evaluate the serum creatinine, cystatin C and creatinine clearance according to Schwartz Formula., Results: We analyzed 103 blood samples of 26 patients. We detected a significant statistical correlation between serum creatinine and cystatin C (r = 0.81, p < 0.0001), cystatin C and creatinine clearance estimated by stature (r = -0.84, p < 0.0001) and between serum creatinine and creatinine clearance estimated by stature (r = -0.97, p < 0.0001)., Conclusions: The expensive measurement of cystatin C showed no advantage in relation to serum creatinine and creatinine clearance according to Schwartz Formula in cystinosis patients to estimate the glomerular filtration rate. This is the first report checking the value of serum creatinine, creatinine clearance estimated by stature and cystatin C in cystinosis patients.

Background: Some studies have reported a decreased absorption of mycophenolic acid (MPA) from mycophenolate mofetil (MMF) in renal transplanted (RTx) patients under proton-pump inhibitors (PPIs). There is still a lack of information regarding (1) whether this effect occurs when MMF is administered with either tacrolimus or cyclosporine A [calcineurin inhibitors (CNIs)], (2) whether the effect has the same amplitude during the first year after RTx, and finally (3) whether this decrease in exposure is clinically relevant., Methods: We retrospectively analyzed the omeprazole effect in 348 12-hour pharmacokinetic samplings [area under the curve (AUC)(0-12h)] performed on days 7, 14, 30, 60, 180, and 360 after RTx in 77 patients who participated in previous trials., Results: For all periods, the groups with and without PPI did not differ in all variables. By mixed-model analysis of variance, PPI reduced the MPA AUC(0-12h) (P < 0.0008) in the patients under both CNIs mainly due to decreased absorption (P = 0.049). In the tacrolimus group, a lower exposure seemed also due to a decreased MPA reabsorption at 10-12 hours. The PPI effect remains throughout the first year but was clinically more important on day 7. By Cox analysis, the use of PPI was associated with a 25% less chance of being adequately exposed to MPA (95% confidence interval 0.58-0.99, P = 0.04). Similarly, the number of patients underexposed to MPA (AUC < 30 ng·h/mL) was higher at most periods in the PPI group but again not statistically significant., Conclusions: These data indicate that PPI decreases the MPA exposure when associated with both CNIs but particularly in the first week after RTx. In this period, the MMF dose should be increased. This effect lasts throughout the first year but does not seem to be clinically relevant after the first week.

Introduction: Tourniquet due venous stasis can alter both concentration and/or activity of several blood analytes, but is rarely regarded as an issue of laboratory variability. To overcome the problem transillumination devices (TD) have been proposed for a stasis-free phlebotomy. In this paper the use of a TD in place of tourniquet during blood collection has been evaluated., Materials and Methods: Blood was collected from 250 volunteers divided in five homogenous groups of tourniquet times (G1: 30 sec, G2: 60 sec, G3: 90 sec, G4:120 sec, G5: 180 sec) and compared to blood obtained using TD. All samples were analyzed for glucose (GLU), total protein (TP), albumin (ALB), triglycerides (TRIG), potassium (K), sodium (NA), phosphate (PHOS), calcium (CA), alkaline phosphatase (ALKP) and magnesium (MG)., Results: In respect of TD, G1 did not show statistically significant increases in all clinical chemistry tests; G2 showed increases for GLU, TP, ALB, TRIG, K, CA, MG and ALKP. G3 and G4, showed no significant increase only for PHOS. G5 showed significant increases in all the tests evaluated. Moreover, clinically significant variations were observed for TP, ALB, K and CA in G2 to G5; for NA in G3 to G5; for MG in G4 and G5; for GLU, TRIG, ALKP only in G5., Conclusions: These results support the application of TD in blood collection for routine clinical chemistry laboratory tests, suggesting its use should be more diffused.

Changes in urinary porphyrin excretion may be the result of hereditary causes and/or from environmental or occupational exposure. The objective of this study was to measure the amount of some porphyrins in spot urine samples obtained from volunteers randomly selected from a healthy adult population of São Paulo with a sensitive HPLC method and to estimate normal ranges for a non-exposed population. Spot urine samples were collected from 126 subjects (both genders, 18 to 65 years old) not occupationally exposed to porphyrinogenic agents. Porphyrin fractions were separated on RP-18 HPLC column eluted with a methanol/ammonium acetate buffer gradient, pH 4.0, and measured fluorometrically (excitation 405 nm/emission 620 nm). The amount of porphyrins was corrected for urinary creatinine excretion. Only 8-carboxyl (uro) and 4-carboxyl (copro) porphyrins were quantified as microg/g creatinine. Data regarding age, gender, occupational activities, smoking and drinking habits were analyzed by Mann-Whitney and Kruskal-Wallis tests. Uroporphyrin results did not differ significantly between the subgroups studied. Copro and uro + copro porphyrins were significantly different for smokers (P = 0.008) and occupational activities (P = 0.004). With respect to alcohol consumption, only men drinking >20 g/week showed significant differences in the levels of copro (P = 0.022) and uro + copro porphyrins (P = 0.012). The 2.5-97.5th percentile limit values, excluding those for subjects with an alcohol drinking habit >20 g/week, were 0-20.8, 11.7-93.1, and 15.9-102.9 microg/g creatinine for uro, copro and uro + copro porphyrins, respectively. These percentile limit values can be proposed as a first attempt to provide urinary porphyrin reference values for our population, serving for an early diagnosis of porphyrinopathies or as biomarkers of exposure to porphyrinogenic agents.

In this study, the elements Br, Ca, Cl, Fe, Na, Rb, Se and Zn were determined in serum of a healthy elderly population residing in the São Paulo Metropolitan area, using instrumental neutron activation analysis. Comparison studies indicated that only Se concentration was significantly lower in the elderly group aged 75-91 years than those obtained for the group aged 60-74 years. Between genders, males presented lower Br concentrations and, the females lower Fe. Mean concentrations obtained for most elements were within the values reported in the literature.

Background: There is little information regarding the 12-h mycophenolic acid (MPA) pharmacokinetics (PK), a way to monitor the drug and the need of frequent monitoring, in stable patients., Methods: A cohort of 35 adults, under long-term mycophenolate mofetil (MMF) therapy plus cyclosporin A (n = 12), TACimus (n = 12) or MMF only (n = 11); all with prednisone had a 12-h MPA-PK performed to ascertain the percentage of them within a defined therapeutic window. In 13 other patients, two PK studies undergone 1 wk apart were performed to evaluate the need for frequent measurements., Results: Fourteen (40%) patients were within the defined therapeutic window (36-60 microg h/mL). Nine patients (26%) were overexposed while 12 (34%) were underexposed. A Cmax> or =10 microg/mL was seen in 20 (57%) of the patients. These percentages were equally distributed between the treatment groups both for AUC0-12 and Cmax. The equations using C0, C2 or both predict exposure, although the use of C2 seems to be more adequate in clinical practice. There were no differences in MPA exposure in patients with a repeated PK evaluated 1 wk later., Conclusion: The use of MMF without monitoring MPA blood levels may cause over-/underexposure to the drug in stable recipients. However, in patients under MMF for more than 1 yr, MPA levels are stable and there is no need for frequent measurements.

New cyclosporine A (CsA) formulations must prove their bioequivalence to Neoral, the reference CsA formulation, to allow free prescription for the patients. The aim of this study was to compare the pharmacokinetics (PK) of a new CsA formulation (Zinograf-ME), produced by Strides-Arcolab, to Neoral and to demonstrate their interchangeability in stable renal transplant recipients. Twelve-hour PK studies were obtained from 18 (13 M/5 F) adult patients (mean age 44.7 +/- 12 years). They received their renal allografts from 13 cadaver and 5 living donors. Before enrollment, all patients were receiving a third generic CsA for a mean of 48 months. Nine patients were also under azathioprine and 9 under mycophenolate mofetil; 17 received prednisone. A single oral dose of either Zinograf or Neoral was administered. The first PK study was performed with one formulation, and 1 week later, a second PK was done with the other formulation. During the washout period, patients continued taking the third CsA formulation. The drug substitution was done milligram-for-milligram. The CsA whole-blood level was measured by TDx immunoassay. Mean +/- SD of area under the curve (AUC), maximum concentration (C(max)), and concentration at the second hour (C2) of Zinograf were not statistically different from those with Neoral (4019 +/- 1466 vs 3971 +/- 1325 ng x h/mL, 998 +/- 376 vs 1021 +/- 356 ng/mL, and 707 +/- 254 vs 734 +/- 229 ng/mL, respectively). In the same way, the Zinograf 90% confidence interval for either C(max) (-123, +77 ng/mL) or AUC (-214, +311 ng.mL/h) were within the Neoral bioequivalence interval for the same parameters (+/-204 ng/mL and +/-794 ng x mL/h, respectively). These data demonstrate that the ZinografME CsA formulation is bioequivalent to Neoral.

Tradescantia pallida cv. purpurea, a plant species widely employed for ornamentation in Brazil, has been successfully used for monitoring the genotoxicity of various agents by the micronucleus assay. To amplify knowledge about its suitability as a bioindicator species, its capacity for accumulating trace elements from urban air pollution was evaluated. T. pallida was rooted using standardized soil, and the vases were distributed in two highly polluted sites of the urban area of São Paulo, Brazil (Cerqueira Cesar and Congonhas districts), and in one unpolluted control site situated approximately 50 km from downtown São Paulo (in Caucaia do Alto). Approximately six months after exposure to pollutants, adult leaves of this plant were collected monthly for 12 months. The leaves were washed with deionized water, dried, and ground for analyses. Characterization of element levels was carried out by neutron activation analysis. Powdered samples and standards were irradiated at the IEA-R1 nuclear reactor for short and long periods, and concentrations of As, Ba, Br, Ca, Ce, Cl, Cr, Co, Fe, K, La, Mn, Na, Rb, Sb, Sc, Sr, Th, and Zn were determined. Analysis of variance applied to the results indicated that samples from polluted sites present the highest concentrations of Ba, Ce, Cr, Co, Fe, La, Sb, and Sc (p < 0.05). Discriminant analysis revealed that it was possible to distinguish the two polluted areas with a precision of 97.5%, based on the amount of pollutant elements measured in the plants at each site. The results indicated the potential use of T. pallida as an accumulator plant for air pollution biomonitoring.

Mycophenolate mofetil (MMF) is given to children in fixed doses based either on body weight or body surface area. There are data indicating mycophenolic acid (MPA) blood levels should be monitored in the early period of transplantation. However, there is little information regarding MPA pharmacokinetics (PK) in stable pediatric recipients. We evaluated MPA-PK in 20 stable renal transplant children (11.7+/-1.9 years) under long-term (46+/-31 months) MMF (26.1+/-7 mg/kg per day or 785+/-183 mg/m(2) per day) therapy plus prednisone and cyclosporin A (n=16), tacrolimus (n=3), or MMF/prednisone (n=1). Total MPA levels were measured using the EMIT-MPA assay at 0, 1, 2, 3, 4, 6, and 8 h after an oral dose of MMF. The level at 12 h was considered equal to the trough level for AUC(0-12) calculation. Mean C(0), C(max), AUC (0-12), and T(max )were 3.46+/-1.32, 13.5+/-0.58 microg/ml, 63.2+/-24.4 microg x h/ml, and 1.3+/-0.6 h, respectively. Six (30%) children were considered to have an adequate exposure (36-54 microg x h/ml) to MPA, 11 (55%) showed an AUC(0-12 )>54 microg.h/ml, and 3 (15%) showed an AUC(0-12 )<36 microg x h/ml. A C(max )>/=10 microg/ml was seen in 13 (65%) children. MMF dose did not correlate with AUC(0-12) or C(max). The combination of variables C(0), C(1), and C(4 )provided an equation to predict exposure (r(2)=0.75) where AUC(0-12)=12.62+(7.78 x C(0))+(0.90 x C(1))+(1.30 x C(2)) (P<0.001). The use of MMF without monitoring MPA blood levels may cause unnecessary overexposure to the drug in stable pediatric recipients.