ABSTRACT
The clearance of sulphamethoxazole (SMX), a compound metabolised primarily by the N-acetyltransferase NAT1, is increased in cystic fibrosis (CF) patients. We assessed the activity and kinetic properties of NAT1 in lysates of peripheral blood mononuclear leukocytes (MNL) from CF (n = 17) and control (n = 22) subjects using SMX and p-aminobenzoic acid (PABA) as test substrates. The Km and Vmax values of both substrates in MNL from CF patients and control subjects were not significantly different. The acetylation of PABA (100 microM) by intact MNL from CF patients (n = 4) was not different from the observed in intact MNL from controls (n = 9) (25 +/- 3 pmol h-1 per 10(6) MNL vs 27 +/- 4 pmol h-1 per 10(6) MNL). These results suggest that there are not systemic changes in this enzyme in CF. The increased metabolic clearance of SMX may therefore be related to factors other than alterations in the level of activity of the N-acetyltransferase NAT1.
Subject(s)
4-Aminobenzoic Acid/metabolism , Arylamine N-Acetyltransferase/blood , Cystic Fibrosis/enzymology , Leukocytes, Mononuclear/enzymology , Sulfamethoxazole/metabolism , Acetylation , Adolescent , Adult , Centrifugation, Density Gradient , Chromatography, High Pressure Liquid , Computer Simulation , Female , Humans , Hydrogen-Ion Concentration , MaleABSTRACT
A large proportion of patients attending our adult cystic fibrosis (CF) clinic have lung colonization with P. cepacia. We present a review of these patients with regard to clinical course and survival, lung function and immunological parameters. Twenty-two of 44 patients (50 percent) have P. cepacia colonization (17 males, 5 females, aged 20-33 years). All patients acquired the organism after the age of 10 years with 17 of 22 (77 percent) acquiring it after the age of 15 years. All but one patient were followed up in the same paediatric CF clinic with documented acquisition before transfer to the adult clinic. Both members of the one pair of siblings are colonized. Three of 22 (14 percent) are also colonized with other organisms (P. aeruginosa, 1; P. maltophilia, 1; S. aureus, 1). There was no significant difference in frequency of hospitalizations or lung function tests between patients with and without P. cepacia. However, patients with P.cepacia had significantly higher ESR, C-reactive protein and immunologlobulin than those without P.cepacia. To date, two of 22 (9 percent) with P.cepacia have died as a result of deteriorating lung disease. P.cepacia has become a more common pathogen in our adult CF patients. It appears to be nosocomially acquired and although not specifically associated with increased mortality may be associated with a more severe immunological response. However, in this setting, it presents a greater challenge for control of acquisition and selection of antimicrobial therapy (AU)
