Estimated glomerular filtration rate for drug dose adjustment: Cockcroft and Gault or abbreviated MDRD equation?

OBJECTIVES: Evaluate if Cockcroft and Gault (CG) estimated glomerular filtration rate (eGFR) might be replaced by abbreviated MDRD eGFR for drug dose adjustment. DESIGN AND METHODS: eGFR was determined in 140 hospitalized patients (median: 68 years, 65 kg) treated by nephrotoxic and/or renally cleared drugs. RESULTS: CG eGFR was 61 mL/min vs. 78 mL/min/1.73 m(2) for MDRD (p<0.0001). CG-MDRD difference ranged from -93 to +34 mL/min, influenced by patient age, weight, and gender (p<0.001). CONCLUSIONS: CG eGFR cannot be easily replaced by abbreviated MDRD eGFR for drug dose adjustment.

Effects of a short-course of amoxicillin/clavulanic acid on systemic and mucosal immunity in healthy adult humans.

Although amoxicillin/clavulanic acid (AMC) is the most frequently administered antibiotic in France, its in vivo effects on immunity in healthy adults have never, to our knowledge, been described. Eighteen healthy adult male volunteers, 25+/-6 years old, were treated for 5 days with oral amoxicillin (1 g) /clavulanate potassium (125 mg), two times daily. Systemic and local intestinal immunity parameters were sequentially explored before, during and after the antibiotic treatment. No significant differences were obtained for transudation markers (albumin and alpha1-antitrypsin) in sera, feces and saliva, showing that AMC did not induce inflammatory reaction. Phagocytosis, peripheral blood cell subsets, intracellular interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha production by natural killer (NK) cells and cytotoxic T lymphocytes, intracellular TNF-alpha production by monocytes showed no significant differences throughout the trial. In fecal outputs, no significant differences were found in secretory immunoglobulin A (S-IgA), lactoferrin (Lf), lysozyme (Lz) and transforming growth factor (TGF)-beta1. In sera, concentrations of total IgA (T-IgA), S-IgA, IgM, Lf and Lz did not show any significant variations throughout the study, whereas concentrations of IgG were slightly but significantly reduced 15 days after AMC treatment. In saliva, concentrations of T-IgA were slightly but significantly higher, whereas S-IgA concentrations were unchanged. Our results showed that oral AMC intake did not induce any significant adverse effects on immunity in adult humans.

New sensitive method for the measurement of lysozyme and lactoferrin for the assessment of innate mucosal immunity. part I: time-resolved immunofluorometric assay in serum and mucosal secretions.

Mucous peristalsis, mucus and immunity proteins, such as lysozyme and lactoferrin, are part of humoral innate immunity. The aim of this study was to develop a quantitative method, a time-resolved-immunofluorometric assay, to measure lysozyme and lactoferrin in sera, saliva, stools and cervico-vaginal secretions. This method was validated in 51 healthy subjects. Linearity for lysozyme was between 1.02 and 25 microg/l and for lactoferrin between 1.02 and 100 microg/l. The detection limit was 0.5 microg/l for lysozyme and 1 microg/l for lactoferrin. Albumin and alpha1-antitrypsin were measured by immuno-nephelometry to calculate salivary, intestinal and cervico-vaginal coefficients of excretion. Lysozyme and lactoferrin were present in all types of mucosal surfaces. Very high concentrations of lysozyme and lactoferrin were found in cervico-vaginal fluid (166.2 and 72.7 mg/l, respectively), compared to the concentrations found in the other mucosal fluids. Lysozyme in stools was produced at the rate of 0.42 mg/d compared to 0.02 mg/d lactoferrin production. Lysozyme and lactoferrin greatly exceeded the values expected from the molecular weight-affected seepage from plasma, suggesting primarily local synthesis in healthy subjects. Quantitative measurement of lysozyme and lactoferrin can aid in the assessment of the activity of mucus-associated lymphoid tissues in innate immunity, and can help in further understanding of the role of these proteins in mucosal diseases.

New sensitive method for the measurement of lysozyme and lactoferrin to explore mucosal innate immunity. Part II: time-resolved immunofluorometric assay used in HIV patients with oral candidiasis.

The aim of this study was to explore lysozyme and lactoferrin concentrations in human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis (OPC). These proteins were measured by time-resolved immunofluorometric assay, validated in Part I of this study, in paired serum and salivary secretions of 30 patients. Eleven HIV-positive patients without OPC, eight HIV-positive patients with OPC and eleven HIV-negative healthy subjects were included in the study. The relative coefficient of excretion of salivary albumin was used to establish protein origin. In serum, the low lactoferrin concentrations in HIV-infected patients with and without OPC (0.610 mg/l (p < 0.05) and 0.896 mg/l (p < 0.01) vs. 1.439 mg/l in healthy subjects) were probably due to a decrease in nonspecific immunity, particularly the polymorphonuclear cells. In HIV-infected patients with OPC, the high salivary lysozyme and lactoferrin concentrations (170.94 mg/l and 66.48 mg/l vs. 23.35 mg/l and 10.20 mg/l in healthy subjects, respectively) and their mean relative coefficient of excretion of above 1 indicated a high local production of lysozyme and lactoferrin in saliva. The development of OPC in HIV-infected patients could be a consequence of inefficient lysozyme and lactoferrin concentrations and of decreased cooperation between innate and adaptative immune systems.