Browsing by Author "Sousa, E"
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- Augmented renal clearance in septic patients and implications for vancomycin optimisationPublication . Baptista, JP; Sousa, E; Martins, PJ; Pimentel, JMThe aim of this study was to evaluate the effect of augmented renal clearance (ARC) on vancomycin serum concentrations in critically ill patients. This prospective, single-centre, observational, cohort study included 93 consecutive, critically ill septic patients who started treatment that included vancomycin by continuous infusion, admitted over a 2-year period (March 2006 to February 2008). ARC was defined as 24-h creatinine clearance (CL(Cr))>130mL/min/1.73m(2). Two groups were analysed: Group A, 56 patients with a CL(Cr)≤130mL/min/1.73m(2); and Group B, 37 patients with a CL(Cr)>130mL/min/1.73m(2). Vancomycin therapeutic levels were assessed on the first 3 days of treatment (D(1), D(2) and D(3)). Serum vancomycin levels on D(1), D(2) and D(3), respectively, were 13.1, 16.6 and 18.6μmol/L for Group A and 9.7, 11.7 and 13.8μmol/L for Group B (P<0.05 per day). The correlation between CL(Cr) and serum vancomycin on D(1) was -0.57 (P<0.001). ARC was strongly associated with subtherapeutic vancomycin serum concentrations on the first 3 days of treatment.
- Benign and malignant mammary tumors induced by DMBA in female Wistar ratsPublication . Dias, M; Cabrita, S; Sousa, E; França, B; Patrício, J; Oliveira, CFThis study pretends to characterize 7, 12-dimetylbenz[a]anthracene-induced benign and malignant tumors. One hundred and twenty female Wistar rats were randomly allocated to two groups: Control Group and Induction Group; IG animals were given a single dose of DMBA and killed 24 weeks after. Other tumors besides breast tumors were diagnosed, mainly tumors of the salivary glands and ovarian benign epithelial tumors. Incidence of breast disorders was about 60%. Macroscopic mammary tumors varied in dimension from 2 mm to 55 mm. Malignant breast tumors (n = 56) were essentially invasive ductal carcinomas (91.1%), G1 (92.2%), presenting histologic characteristics of good prognosis. Predominant benign breast disorders consisted of glandular (68.6%) and atypical (20%) hyperplasias reproducing histologic types of human breast diseases. Different individual susceptibility to DMBA apparently occurs; while some rats never developed neoplasias, others exhibited several tumors.
- Chemoprevention of DMBA-Induced Mammary Tumors in Rats by a Combined Regimen of Alpha-Tocopherol, Selenium, and Ascorbic AcidPublication . Dias, MF; Sousa, E; Cabrita, S; Patrício, J; Oliveira, CFThis experimental study was designed to evaluate the efficacy of associated naturally occuring antioxidants in the prevention of chemically induced breast cancer using DMBA in virgin female Wistar rats. Rats were randomly allocated to three groups: control group (CG; n = 20), induction group (IG; n = 100), and prevention group (PG; n = 70). A single dose (65 mg/kg) of DMBA was administered in the IG and PG animals at 50 days of age. PG animals also received a single dose of alpha-tocopherol (200 mg/rat) 1 hour after DMBA administration and an association of selenium (p-XSC, 40 ppm/day/rat) and ascorbic acid (540 mg/day/rat) in drinking water, daily, from carcinogenic induction until necropsy. Macroscopic study and pathology revealed a significantly lower development of neoplasms in the PG animals (p < 0.05); the number of rats with mammary tumors, breast cancer incidence, and the number of malignant breast tumors per rat as well as per tumor-bearing rat were significantly decreased in the PG animals. Other types of primary neoplasms existing in the IG animals totally disappeared in the PG animals. Immunostaining to hormone steroid receptors (ER and PR) and cathepsin D was similar in both groups. Overexpression of p53 and metallothioneine was significantly increased in the PG animals (p < 0.05) and immunostaining to bromodeoxiuridin and Ki-67 was also stronger in the remaining tumors in the PG animals. These data thus add to the accumulating evidence that those micronutrients in combination seem to be effective in reducing the incidence of malignant tumors. Nevertheless, remaining tumors seem to present more aggressive behavior and characteristics of drug resistance
- A comparison of estimates of glomerular filtration in critically ill patients with augmented renal clearancePublication . Baptista, JP; Udy, AA; Sousa, E; Pimentel, J; Wang, L; Roberts, JA; Lipman, JINTRODUCTION: Increasingly, derived estimates of glomerular filtration, such as the modification of diet in renal disease (MDRD) equation and Cockcroft-Gault (CG) formula are being employed in the intensive care unit (ICU). To date, these estimates have not been rigorously validated in those with augmented clearances, resulting in potentially inaccurate drug prescription. METHODS: Post-hoc analysis of prospectively collected data in two tertiary level ICU's in Australia and Portugal. Patients with normal serum creatinine concentrations manifesting augmented renal clearance (ARC) (measured creatinine clearance (CLCR) > 130 ml/min/1.73 m2) were identified by chart review. Comparison between measured values and MDRD and CG estimates were then undertaken. Spearman correlation coefficients (rs) were calculated to determine goodness of fit, and precision and bias were assessed using Bland-Altman plots. RESULTS: Eighty-six patients were included in analysis. The median [IQR] measured CLCR was 162 [145-190] ml/min/1.73 m2, as compared to 135 [116-171], 93 [83-110], 124[102-154], and 108 [87-135] ml/min/1.73 m2 estimated by CG, modified CG, 4-variable MDRD and 6-variable MDRD formulae. All of the equations significantly under-estimated the measured value, with CG displaying the smallest bias (39 ml/min/1.73 m2). Although a moderate correlation was noted between CLCR and CG (rs = 0.26, P = 0.017) and 4-variable MDRD (rs = 0.22, P = 0.047), neither had acceptable precision for clinical application in this setting. CG estimates had the highest sensitivity for correctly identifying patients with ARC (62%). CONCLUSIONS: Derived estimates of GFR are inaccurate in the setting of ARC, and should be interpreted with caution by the physician. A measured CLCR should be performed to accurately guide drug dosing.
- Decreasing the time to achieve therapeutic vancomycin concentrations in critically ill patients: developing and testing of a dosing nomogramPublication . Baptista, JP; Roberts, JA; Sousa, E; Freitas, R; Deveza, N; Pimentel, JINTRODUCTION: Achievement of optimal vancomycin exposure is crucial to improve the management of patients with life-threatening infections caused by susceptible Gram-positive bacteria and is of particular concern in patients with augmented renal clearance (ARC). The aim of this study was to develop a dosing nomogram for the administration of vancomycin by continuous infusion for the first 24 hours of therapy based on the measured urinary creatinine clearance (8 h CLCR). METHODS: This single-center study included all critically ill patients treated with vancomycin over a 13-month period (group 1), in which we retrospectively assessed the correlation between vancomycin clearance and 8 h CLCR. This data was used to develop a formula for optimised drug dosing. The efficiency of this formula was prospectively evaluated in a second cohort of 25 consecutive critically ill patients (group 2). Vancomycin serum concentrations between 20 to 30 mg/L were considered adequate. ARC was defined as 8 h CLCR more than 130 ml/min/1.73 m(2). RESULTS: The incidence of ARC was 36% (n = 29/79) and 40% (10/25) in group 1 (n = 79) and 2 (n = 25), respectively. The mean serum vancomycin concentration on day 1 was 21.5 (6.4) and 24.5 (5.2) mg/L, for both groups respectively. On the treatment day, vancomycin plasma clearance was 5.12 (1.9) L/h in group 1 and correlated significantly with the 8 h CLCR (r(2) = 0.66; P < 0.001). The achievement of adequate vancomycin serum concentrations in group 2 was 84% (n = 21/25) versus 51% (n = 40/79) - P < 0.005. CONCLUSIONS: This new vancomycin nomogram enabled the achievement of adequate serum concentrations in 84% of the patients on the first day of treatment.
- Undifferentiated connective tissue disease: a seven-center cross-sectional study of 184 patientsPublication . Vaz, CC; Couto, M; Medeiros, D; Miranda, L; Costa, J; Nero, P; Barros, R; Santos, MJ; Sousa, E; Barcelos, A; Inês, LThe purpose of this study was to characterize the clinical and serological features of a large cohort of patients with antinuclear antibody (ANA) positive undifferentiated connective tissue disease (UCTD). Consecutive patients with UCTD, followed up at the Rheumatology Clinic of the participating centers, were included. Data from these patients were obtained by clinical evaluation and chart review. All patients were diagnosed as having UCTD on basis of the following criteria: positive ANA plus at least one clinical feature of connective tissue disease, but not fulfilling classification criteria for any differentiated connective tissue disease. One hundred eighty-four patients were studied (female patients-94.5%; mean age at time of evaluation-47 years). The most prevalent manifestations were arthralgia (66%), arthritis (32%), Raynaud's phenomenon (30%), sicca symptoms (30%), and leukopenia (19%). The prevalence of ANA was 100%, anti-SSA 20%, anti-dsDNA 14%, and anti-SSB 7%. Patients with anti-dsDNA/anti-Sm, anticentromere/anti-Scl70, or anti-SSA/anti-SSB antibodies more frequently presented a set of manifestations close to systemic lupus erythematosus (SLE), systemic sclerosis, or Sjögren syndrome, respectively. We analyze a large cohort of UCTD. Seventy-two percent of these UCTD patients present lupus-, scleroderma-, or Sjögren-like features but do not fulfill classification criteria and mostly present a mild disease.