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Biomedical subjects

C Warren

Publications and source records attributed to C Warren.

At least 91 records · Page 5Linked to original sources

Immune complexes in early arthritis. II. Immune complex constituents are synthesized in the synovium before rheumatoid factors.

Synovial fluids and paired sera taken from patients either before, after or at the time of diagnosis of definite rheumatoid arthritis (RA) were compared with samples from patients with unclassified inflammatory arthropathies (IA). Raised levels of immune complexes (IC) were detected in some RA patients by C1q binding activity but in the majority of both RA and IA patients by the platelet aggregation test; levels were usually higher in joint fluids than in sera. IgM rheumatoid factors (RF) and IgA RFs were lower in synovial fluids but IgF RF levels were similar in matched samples. Synovial fluid to serum albumin ratios were used to estimate synovial permeability (inflammation) and then to calculate which patients synthesized macromolecules locally in the synovium. Local synthesis of RFs was detected in a greater proportion of RA than IA patients and only two patients formed RFs locally in the first months of symptoms. Half the patients in both groups however appeared to synthesize or trap IC constituents and in many patients there was evidence of local synthesis within 6 months after their symptoms had started. We conclude that local synthesis of large amounts of RFs is uncommon in the early stages of RA but that IC of unknown composition are synthesized or localized in the affected joints of many patients with RA and inflammatory arthropathies shortly after their symptoms appear.

Adolescent↗

Measurement of serum glycosaminoglycans by laser nephelometry.

A simple, sensitive micromethod for the assay of serum hyaluronic acid and chondroitin sulphates is presented. The method is based on the binding of the quaternary ammonium salt, cetylpyridinium chloride (CPC) to serum polyanions, and quantitation of the complexes by laser nephelometry. Measurement of the CPC complexes in serum before and after digestion with specific enzymes enables quantitation of hyaluronic acid and chondroitin sulphates in less than 100 microliters serum. Using this technique, hyaluronic acid is detectable in a small number of normal human sera at concentrations up to 4 mg/l, and chondroitin sulphates are consistently present at concentrations ranging from 2 to 25 mg/l.

Carbazoles↗

The use of concanavalin A to measure acute phase proteins by laser nephelometry.

Concanavalin A (con A) binds specifically to alpha-D-glucosyl, alpha-D-mannosyl and sterically related structures. Many serum glycoproteins contain such residues and will therefore bind and precipitate con A. Using this principle, a nephelometric method was developed for measuring total con A binding proteins in serum. The effect of parameters such as con A to glycoprotein ratio, polymer enhancement, reaction time, stability of the complexes and potential inhibitory molecules such as glucose and calcium were assessed. A brief clinical evaluation of the assay in human sera showed that con A binding correlates well with specific acute phase protein-changes in inflammatory disease and may be used as an index of disease activity. Preliminary studies show that con A binding also reflects disease activity in a number of animal species and thus may provdie a much needed index of inflammation in the experimental animal and in veterinary practice, where species specific antisera to acute phase proteins are not widely available and protein analyses have been rather neglected. The assay is rapid, cheap and may be performed on automated nephelometric systems.

Adult↗

In vitro antibacterial activity and susceptibility of the cephalosporin Ro 13-9904 to beta-lactamases.

The in vitro activity of Ro 13-9904 was assessed against clinical isolated of common bacteria. Its activity against most enterobacteria was similar to that of cefotaxime and moxalactam, but it was even more active than these compounds against all Proteus species. It was also highly active against Haemophilus influenzae and Neisseria gonorrhoeae, including beta-lactamase producers. Like cefotaxime and moxalactam, Or 13-9904 was approximately eightfold more active than carbenicillin against most isolates of Pseudomonas aeruginosa and also active against highly carbenicillin-resistant isolates, but it was relatively inactive against moderately carbenicillin-resistant isolates. Ro 13-9904 also resembled cefotaxime and moxalactam in that it was active, though less so than cephaloridine, against staphylococci and streptococci, except for methicillin-resistant staphylococci and Streptococcus faecalis, which were resistant to it. It was less active than cefoxitin but slightly more active than ampicillin against both Bacteroides fragilis and other Bacteroides spp. Ro 13-9904 was resistant to most beta-lactamases but was attacked by enzymes from B. fragilis, isolates of indole-positive Proteus species, and also by a cefoxitin-hydrolyzing enzyme from an isolate of Enterobacter cloacae.

Bacteria↗

Determination of antibiotic sensitivities by the Sensititre system.

The Sensititre system provides antibiotics dried in microtitre trays in appropriate concentrations for the determination of minimum inhibitory concentrations (MIC) when organisms are added in liquid culture medium and incubated overnight. Results with a variety of media--for Gram-negative bacilli tested with ampicillin, carbenicillin, cephaloridine, and gentamicin, staphylococci with penicillin, cloxacillin, fusidic acid, and gentamicin, and streptococci with penicillin, ampicillin, cephaloridine, and erythromycin--were usually very similar to those of agar dilution tests. Discrepant results are found in a few situations, and in some cases, especially those involving borderline resistance to fusidic acid and gentamicin among staphylococci and Gram-negative bacilli, we have been unable to suggest modfication to produce the right results. Despite these problems, fortunately few and identifiable, we recommend the system especially for use in laboratories that determine the MICs infrequently.

Anti-Bacterial Agents↗

A comparison of methods for the immunoassay of serum apolipoprotein B in man.

Three assays for serum apolipoprotein B, radioimmunoassay, automated immunoprecipitation and rocket immunoelectrophoresis were compared. The antiserum used was raised against lipoprotein of density 1.040-1.053 g/ml (lipoprotein B). Each of the methods had a high degree of specificity when tested against potential interfering substances. The lowest levels of apolipoprotein B could be measured with radioimmunoassay but this sensitivity entailed the use of high dilutions of serum and resulted in a lower precision. Concentration response curves of lipoprotein B solution and serum were parallel for radioimmunoassay and automated immunoprecipitation but were not for rocket immunoelectrophoresis. Serum apolipoprotein B could be assayed by immunoelectrophoresis, however, if serum calibrated against the protein concentration of lipoprotein B solution by either of the other two methods was used as a secondary standard. Such a secondary serum standard also proved advantageous for all the methods because of the relative stability of the apolipoprotein B content of serum as compared to aqueous solutions of lipoprotein B. The mean apolipoprotein B concentration in 29 normolipaemic subjects aged 20-30 years was 0.84 +/- 0.12 g/1 (mean +/- S.D.) by radioimmunoassay, 0.85 +/- 0.11 g/1 by automated immunoprecipitation and 0.88 +/- 0.11 g/1 by rocket immunoelectrophoresis. The correlation between apolipoprotein B levels measured by the three methods was good. The ratio of serum cholesterol to serum apolipoprotein B was unaffected by individual differences in serum cholesterol or triglyceride levels. There was no significant difference between fasting and post-prandial serum apolipoprotein B concentrations. Radioimmunoassay is particularly suited to the measurement of low levels of apolipoprotein B, automated immunoprecipitation for large numbers of samples and rocket immunoelectrophoresis, when care is taken in the interpretation of results, for small numbers of samples.

Apoproteins↗

Antibiotic susceptibilities of streptococci from the mouth and blood of patients treated with penicillin or lincomycin and clindamycin.

Patients undergoing dental extractions were non-randomly allocated to three groups, one of which received no antibiotic, one benzylpenicillin followed by oral penicillin for 5 days, and the third intramuscular lincomycin followed by oral clindamycin. Dental extraction was performed at the beginning of the course of chemotherapy. Streptococci were isolated from the extracted teeth, from blood cultures collected before and immediately after dental extraction, and from sutures removed from the gums 5-7 days after the operation. The species of these organisms was determined, and their susceptibilities to penicillin, clindamycin, cephaloridine, erythromycin and tetracycline were assessed. The majority of streptococci isolated from teeth belonged to the species Streptococcus sanguis, S. mitior, S. mutans and S. milleri. Occasional isolates of each of these organisms collected before the antibiotic could take effect were resistant to penicillin. Three of these species, but not S. mutans, were the commonest streptococci to be isolated from the blood after dental extraction. Penicillin completely suppressed dental bacteriaemia under the conditions of our investigation, and lincomycin reduced the incidence by about 60 per cent. The commonest streptococci from sutures were also S. sanguis, S. mitior, S. mutans and S. milleri. S. faecalis was also isolated, but only in patients who had received antibiotics. Among the non-faecalis organisms, penicillin resistance was significantly more frequent among isolates from patients given penicillin than from patients not given this antibiotic, and clindamycin resistance was significantly more frequent among isolates from patients given lincomycin and clindamycin than from patients not given these antibiotics.

Anti-Bacterial Agents↗

Activity of sulfamethoxazole and trimethoprim against Bacteroides fragilis.

Minimum inhibitory concentrations (MICs) of sulfamethoxazole (SMX) and trimethoprim (TMP), alone and in three combinations, 20:1, 1:1, and 1:20, were determined on Diagnostic Sensitivity Test (DST) and Mueller-Hinton (MH) agars containing lysed blood for various inocula of 91 strains of Bacteroides fragilis from the U.S.A. and U.K. MICs of SMX were high with large inocula and higher on MH than DST, but results for TMP were less affected by these two factors. True SMX resistance was rare: 10 U.S.A. strains previously reported as resistant appeared to be susceptible. Maximum potentiation of MICs was observed when SMX and TMP were combined in ratios close to those of the ratios of their MICs, that is, SMX/TMP 20:1 for large inocula and the reverse for small inocula for determinations on DST and usually 20:1 for all inoculum sizes on MH. These observations explain some of the discrepancies in reports, but defer the problem of potential usefulness of the drugs in the treatment of infection with anaerobes to future study.

Bacteroides fragilis↗