Using 12 different and elaborate broth, agar, and cell culture procedures, we failed to isolate mycoplasmas, ureaplasmas, spiroplasmas, or chlamydiae from the synovial fluid of 10 patients with rheumatoid arthritis (RA) and from six patients with non-rheumatoid arthritis (NRA). In addition, sera from 35 patients with RA and 12 patients with NRA also were examined. Although some of the sera had moderately high titers of metabolism-inhibiting antibody to some of the 10 human Mycoplasma species, especially to the common respiratory pathogen Mycoplasma pneumoniae, and to some of the eight Ureaplasma urealyticum serovars, especially serovars V and VII, there were no significant differences between titers of these antibodies in the two groups of patients. Among RA patients serum antibody titers to M. pneumoniae were 1:32 in five and 1:16 in eight; two patients had higher synovial fluid titers (1:16) than serum titers (1:4). The geometric mean titer (GMT) of antibody to serovar V in synovial fluid was higher in RA patients than in NRA patients, but the difference did not reach significance (P = .056). Reports on the possible role of infectious agents in the pathogenesis of rheumatoid arthritis are reviewed.

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[Standardization and quality control in the evaluation of proliferation parameters in T1T2, N0N1, M0 breast cancer : multicentric retrospective study I. DNA synthesis enzyme activities].

As part of a clinical research project co-ordinated in Grenoble, six French institutions (CRLCC Angers, CHU Grenoble, Hospices civils Lyon, AP Marseille, CRLCC St-Cloud, CHU Tours) grouped together in order to study the following proliferative parameters in primary breast cancer: DNA synthesis enzymes [thymidine kinase (TK), thymidylate synthase (TS)], signal transduction enzyme [protein tyrosine kinase (PTK)] and S-phase fraction (%S). TK, TS and PTK were measured in cytosols using radio-enzymatic biochemical methods. S-phase was estimated using flow cytometry. The first step consisted in standardization and technical validation of the measurements. The second step consisted in the clinical validation by using a retrospective series of 1,003 breast cancers T1T2, N0N1, M0. We report the results of the first step, together with the distributions of the variables and their relationship with classical clinical variables: 1) Using standardized methods and a cytosolic control, a good reproducibility of measurements was obtained, whether assays were performed in one (TS, PTK) or in several laboratories (TK). 2) Significantly different distributions of TK and TS were observed between the different centres mainly due to different conditions of storage of tumours and cytosols. 3) A highly significant correlation was observed between TK, TS and PTK. Highest TK, TS and PTK levels were observed in tumours with high histological grade or receptor negative tumors. This study clearly illustrates the importance of quality assurance of multicentre studies.

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[Standardization and quality control in the evaluation of proliferation parameters in T1T2, N0N1, M0 breast cancer: multicentric retrospective study II. DNA-ploidy and S-phase fraction].

As part of a clinical research project, proliferative parameters were studied in primary breast cancer: standardization and technical validation of thymidine kinase (TK), thymidylate synthase (TS) and protein tyrosine kinase (PTK) are described. A total of 633 frozen tumor specimens, available in four institutions, was analyzed in three flow cytometry laboratories for DNA content and percentage of S-phase cells (%S) measurement. 1) The standardization step consisted in developing a common protocol for sample preparation; then, common cell suspensions were analyzed in order to perform an inter-laboratory control. Objective guidelines were elaborated to interpret DNA histograms in breast carcinoma. 2) DNA-aneuploidy was observed in 61% of cases of the retrospective series. Compared with DNA-aneuploid tumors, mean %S was significantly lower in case of DNA-diploidy (respectively: 6.4% and 2.2%, p < 0.001). When compared between the four institutions, %S distributions did not differ significantly. 3) %S is strongly correlated with TK, TS and PTK and high percentages were also observed in high grade tumors or tumor without hormone receptors. These results show that a standardization in using flow cytometers and DNA software allows multicenter studies.

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Hemodialysis for extracorporeal bicarbonate/CO2 removal (ECBicCO2R) and apneic oxygenation for respiratory failure in the newborn. Theory and preliminary results in animal experiments.

Extracorporeal techniques for respiratory support in the newborn are feasible, as the growth of neonatal extracorporeal membrane oxygenation (ECMO) has demonstrated. It has been shown, however, that even in severely damaged lungs, sufficient oxygenation and gas exchange can be maintained only by removing CO2 in an extracorporeal circuit, i.e., extracorporeal CO2 removal (ECCO2R). To demonstrate the effectiveness of CO2 removal in a bicarbonate-free hemodialysis procedure, CO2 removal was measured during routine acetate hemodialysis in 22 patients on renal replacement therapy for end-stage renal disease. By comparison of predialyzer and postdialyzer total CO2, an overall CO2 removal of 79.1 +/- 15.1 ml/min was measured in the blood and 77.0 +/- 19.5 ml/min in the dialysate; this was approximately one third of the entire metabolic CO2 production and probably accounted for the secondary hypoxia during acetate hemodialysis. To use bicarbonate-free hemodialysis for total metabolic CO2 removal, acetate dialysate was modified with lactate, phosphate buffer, and sodium hydroxide to compensate for the bicarbonate loss. In sheep, apneic oxygenation could be achieved with blood flow rates as low as 10-15 ml/kg/min for 4-6 hours. These preliminary data suggest that a hemodialysis procedure for bicarbonate and CO2 elimination (ECBicCO2R) could be an efficient method for CO2 removal requiring much lower blood flow rates than techniques presently in use.

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