Studies of the action of some anti-inflammatory drugs on complement mediated immune haemolysis.
(17/171)
1 The effects of various anti-inflammatory and non-anti-inflammatory drugs on complement mediated haemolysis have been studied. Drugs which were significantly protein bound were found to inhibit this form of immune lysis, but only at greater concentrations than achieved therapeutically. 2 Removal of the drugs by prolonged dialysis resulted in restoration of complement activity with the exceptions of phenylbutazone and warfarin sodium. 3 Reconstitution experiments indicated that C2 and some of the later components especially C7 were affected by the drugs. 4 Intra-articular injections of prednisolone (100 mg) in patients with rheumatoid arthritis, failed to produce significant changes in the synovial fluid complement system. 5 None of the drugs affected the binding of antibody to antigen, or the ability of sensitized sheep cells to fix complement. (+info)
Generalized seborrhoeic dermatitis. Clinical and therapeutic data of 25 patients.
(18/171)
Twenty-five infants with generalized seborrhoeic dermatitis have been studied with reference to the provision of optimum treatment. Leucocyte counts and chest x-ray examination are recommended in every case. Irrespective of clinical findings, antibiotics should be given to patients with overt bacterial infection and those with leucocytosis, shift to the left, and toxic granulation. One group of infants was treated with vitamin B complex plus biotin given slowly intravenously over 24 hours; a second group was given only biotin intravenously over 2-3 hours; and a third group only biotin over 1-2 minutes. A fourth group was treated with both biotin and antibiotics for confirmed or suspected superimposed bacterial infection. The results were excellent in all groups. Skin lesions improved within 4-8 days and cleared completely within 15-30 days. Intravenous administration of biotin is recommended as less painful and less dangerous than multiple intramuscular injections. (+info)
Diffusion of cloxacillin into synovial tissue.
(19/171)
After a 30 min i.v. infusion of 1 g cloxacillin, the concentrations of this antibiotic were measured in plasma and synovial tissue samples from 11 patients undergoing total hip replacement. Assuming passive distribution between plasma and tissue the rate constants of distribution were estimated. The mean half-life of distribution was 22 min. The concentration of free drug in synovial tissue was estimated to be 77% of the total tissue concentration. The maximum tissue drug concentration after an i.v. bolus dose is predicted to occur at about 37 min. (+info)
WILD-TYPE VARIANTS OF EXOPENICILLINASE FROM STAPHYLOCOCCUS AUREUS.
(20/171)
1. Three variants of staphylococcal exopenicillinase (types A, B and C) can be distinguished on chemical, enzymological and immunological grounds. 2. Enzyme type A has a higher specific activity than that of type B, but has a similar combination affinity with anti-(exopenicillinase type A) serum. 3. Enzyme types A and C have a similar specific activity, but enzyme type C has a lower combination affinity for anti-(exopenicillinase type A) serum than has enzyme type A. 4. The sedimentation coefficients and amino acid analyses of the three enzyme types are similar. 5. All three enzyme types have small but significant differences in kinetics of action when hydrolysing benzylpenicillin, methicillin, cloxacillin and cephalosporin C. 6. Peptide maps, obtained from enzyme types A and C after digestion with trypsin, show that these two variants probably differ in the nature of only a very few amino acid residues. 7. Enzyme type B seems to be confined to staphylococci that are members of staphylococcal phage group II. Enzyme types A and C are produced by staphylococci that are members either of phage group I or III, but never group II. 8. The low specific enzyme activity and affinity of enzyme type B towards all penicillins tested suggest that this enzyme type has a lower ;efficiency' in hydrolysing penicillin and therefore in protecting bacteria from the action of penicillin. This could account for the low incidence among ;hospital staphylococci' of penicillin-resistant staphylococci that are members of phage group II. (+info)
Site-directed mutagenesis and substrate-induced inactivation of beta-lactamase I.
(21/171)
The substrate-induced inactivation of beta-lactamase I from Bacillus cereus 569/H has been studied. Both the wild-type enzyme and mutants have been used. The kinetics follow a branched pathway of the type recently analysed [Waley (1991) Biochem. J. 279, 87-94]. The substrate cloxacillin (a penicillin) formed an acyl-enzyme (characterized by m.s.), and it was probably the instability of this intermediate that brought about inactivation. A disulphide bond was introduced into beta-lactamase I (the wild-type enzyme lacks this bond) by site-directed mutagenesis: Ala-77 and Ala-123 were replaced by cysteine. Spontaneous oxidation yielded the disulphide. The activity of this newly cross-linked enzyme was a little diminished, but the stability towards inactivation by cloxacillin was not increased. A second mutant of beta-lactamase I was studied: this mutant lacked the first 17 residues, i.e. the first alpha-helix. The mutant had reduced activity towards ordinary (non-inactivating) substrates and no hydrolysis of cloxacillin could be detected. These mutant enzymes were expressed in Bacillus subtilis, and were purified from the extracellular medium. (+info)
99mTc-Labeled UBI 29-41 peptide for monitoring the efficacy of antibacterial agents in mice infected with Staphylococcus aureus.
(22/171)
Based on our earlier observation that (99m)Tc-UBI 29-41, a radiolabeled peptide derived from ubiquicidin (UBI), discriminates between infections and sterile inflammatory processes, we considered the possibility that this tracer could be used for monitoring the efficacy of antibacterial agents in animals infected with Staphylococcus aureus. METHODS: We injected (99m)Tc-UBI 29-41 into S. aureus-infected mice after treatment with various doses of cloxacillin or erythromycin. At intervals thereafter, accumulation of the radiolabeled peptide at the site of infection was assessed by scintigraphy. When S. aureus was antibiotic resistant, we evaluated the efficacy of hLF 1-11, an antimicrobial peptide derived from human lactoferrin (hLF), in rats using (99m)Tc-UBI 29-41 and scintigraphy. RESULTS: Decreasing amounts of radiolabeled peptide at the site of the S. aureus infection in animals correlated (r(2) > 0.81; P < 0.001) with increasing doses of cloxacillin in animals. An effective dose of erythromycin resulted in reduced (P = 0.023) accumulation of the radiolabeled peptide at the site of S. aureus infection in mice. In addition, we noted decreasing amounts of (99m)Tc-UBI 29-41 at the site of infection after administration of increasing doses of hLF 1-11 peptide in rats infected with antibiotic-resistant S. aureus. Furthermore, the number of viable bacteria decreased with increasing doses of cloxacillin or hLF 1-11 peptide, and a good correlation (r(2) > 0.80; P < 0.001) between the accumulation of (99m)Tc-UBI 29-41 and the number of viable (antibiotic-resistant) S. aureus at the site of infection was seen. In an attempt to explain these results, we found that these antibacterial agents do not affect the in vitro binding of (99m)Tc-UBI 29-41 to bacteria. Furthermore, this radiolabeled peptide bound to free bacteria and to cell-adherent but not phagocytized S. aureus, suggesting that at sites of infection mainly extracellular bacteria are targeted by (99m)Tc-UBI 29-41. CONCLUSION: (99m)Tc-UBI 29-41 allows the monitoring of the efficacy of antibacterial agents in mice and rats with S. aureus infections. (+info)
Bacteraemia due to Staphylococcus aureus.
(23/171)
AIMS: To describe the clinical features and outcome of bacteraemia due to Staphylococcus aureus in children admitted to a rural Kenyan hospital. METHODS: Retrospective case review of all children with a positive blood culture for S aureus admitted to Kilifi District Hospital, Kenya, between January 1996 and December 2001. RESULTS: Ninety seven children (median age 17 months, range 1 day to 12 years; 46 male) with bacteraemia due to S aureus were identified, accounting for 5% of all positive blood cultures; 10 were considered to be nosocomially acquired. A focus that was clinically consistent with staphylococcal infection was identified in 52 cases; of these, 88% had multiple foci. Children with a focus were likely to be older, present later, and have a longer duration of hospital stay. Most children in this group (90%) received intravenous cloxacillin on admission in contrast to none of those without a focus. In the former group, mortality was only 6% compared to 47% among those without a focus; 10/13 neonates without an apparent staphylococcal focus died compared to none of the 11 with a focus. Eight of the 10 neonates in the former group died within 48 hours of admission, before empirical antibiotics could be changed to include cloxacillin. CONCLUSIONS: Children most at risk of death associated with bacteraemia due to S aureus are least likely to have clinical features traditionally associated with this infection. (+info)
Typing and characterization of carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex in a Chinese hospital.
(24/171)
This study was designed to investigate the prevalence of carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex (Acb complex) and to type carbapenemases. The relatedness of 45 isolates of carbapenem-resistant Acb complex collected from a clinical setting was analysed by PFGE. The carbapenemases produced by these isolates were typed by IEF, a three-dimensional test, 2-mercaptopropanoic acid inhibition assay, PCR and DNA cloning and sequencing. Results showed that all 45 isolates were resistant to multiple antibiotics including meropenem. The resistance rates to cefoperazone/sulbactam and ampicillin/sulbactam were 2.2 and 6.5%, respectively. About 71.7-78.3% of these isolates were intermediately resistant to cefepime, ceftazidime and cefotaxime. Forty-five isolates were classified into type A (98%) and B (2%) based on their PFGE patterns. Most of type A isolates were from the ICU. Type A was the dominant isolate, including subtypes A1 (22%), A2 (71%), A3 (2%) and A4 (2%). Only one isolate, from the haematology department, belonged to type B. Forty-three isolates (96%) were positive for carbapenemase. One isolate had two bands by IEF, the pIs of which were 6.64 and 7.17. The band with the pI of 6.64 was OXA-23. The other 42 isolates produced two bands with pIs of 6.40 and 7.01 which could not be inhibited by clavulanic acid, cloxacillin or 2-mercaptopropanoic acid. It can be concluded that the prevalent carbapenem-resistant Acb complex isolates from this hospital all had similar beta-lactamase patterns. (+info)