Acute phase proteins and clinical synovitis activity in patients with rheumatoid arthritis

Summary A number of laboratory variables, including Hb., ESR and several phase proteins, fluctuated in concord with the clinical signs of synovitis activity in patients with rheumatoid arthritis during a controlled study of 3 disease-modifying anti-rheumatic drugs (DMARD). The correlation between laboratory variables and clinical synovitis was significant in a large patient population but the correlation coefficients were not of such magnitude that any of the laboratory variables reflected clinical synovitis activity in a reliable manner in the individual patients. In patients treated with azathioprine, the response of the Hb, (and consequently of the ESR), was reduced compared to patients given other DMARD. This phenomenon was caused by the bone marrow suppressing effect of azathioprine. However, the effect of azathioprine on the clinical synovitis activity did not differ from that of the 2 other drugs. Similar results were found by reviewing the literature about controlled trials of DMARD. In the present trial the clinical evaluation was performed under optimal conditions. In daily clinical practice the evaluations of the joints may be less than optimal since they may be performed by different rheumatologists with varying experience. Consequently, it may be difficult to do without the unreliable laboratory variables mentioned in the routine assessments of disease activity, unless the quality of routine evaluations of synovitis activity is improved considerably.     

Influence of medical audit on electrodiagnostic evaluation of polyneuropathy. A multicentre study.

OBJECTIVE: Since 1992, 7 European neurophysiologists have participated in the ESTEEM project concerned with improvements in electrodiagnostic medicine. This study assesses whether the collaboration that includes peer review medical audit has influenced the involved physicians' electrodiagnostic criteria for polyneuropathy (PNP) diagnosing and classification. METHODS: Two sets of each physician's PNP examinations performed early and late in the study were examined for changes in (1) number of studies with abnormal electrophysiological findings required for diagnosing PNP, and (2) agreement between the classifications given by the individual physicians and the peer review group. RESULTS: The average number of abnormal motor nerve segments per patient increased from 4.6 to 6.4 during the study. Although most individual changes were minor, the second set of examinations showed an increased homogeneity among the physicians in the number of abnormal motor nerve segments and abnormal F wave studies, and a tendency towards increased homogeneity in the number of abnormal sensory nerve segments. There was also an increased agreement on pathophysiological PNP classification in the second set of examinations compared to the first set. CONCLUSIONS: The participation in the ESTEEM project seems to have impacted the physicians' clinical routine, possibly as they have accustomed themselves to apply criteria more strictly. SIGNIFICANCE: This study support that international collaboration is a useful step towards improvements in electrodiagnostic medicine.     

Evidence for xylitol 5-P production in human dental plaque

The Turku sugar studies indicated that xylitol may possess a caries-therapeutic effect. More recent data show that xylitol exhibits a bacteriostatic activity on a wide range of bacteria based on uptake and expulsion of xylitol. Intracellular xylitol 5-P appears to be a key substance associated with inhibition of bacterial metabolism by xylitol. This has been shown in studies with pure strains of bacteria, mainly Streptococcus mutans . The aim of the present study was to examine if production of xylitol 5-P occurs in freshly collected dental plaque which is exposed to labeled xylitol. Plaque extracts were analyzed by thin-layer chromatography combined with autoradiography and high performance liquid chromatography. Strong indications were obtained that xylitol 5-P is readily produced by dental plaque. No other significant xylitol metabolites were identified. The bacteriostatic properties of xylitol in plaque are a mechanism which may well account for the caries-therapeutic effect of xylitol.     

Preparation of protein loaded poly(D,L-lactide-co-glycolide) microparticles for the antigen delivery to dendritic cells using a static micromixer.

The cellular immune response against tumors, viruses, or intracellular bacteria requires adequate antigen delivery to professional phagocytes, their processing and the presentation of antigenic peptides to T-cells. Biodegradable microparticles to enhance antigen phagocytosis and the response of cytotoxic lymphocytes have been proposed. The aim of the present study was to formulate poly(lactide-co-glycolide) (PLGA) microparticles using a w/o/w solvent evaporation procedure in order to obtain suitable vehicles for vaccination. Bovine serum albumin bearing fluorescein isothiocyanate (FITC-BSA) was used as a model antigen. For microparticle preparation a static micromixer was employed. Microparticles of 2-3 microm can be produced with good reproducibility by applying high flow rates at the micromixer. Microparticles with a smooth surface and only one pore were observed using scanning electron microscopy (SEM). Confocal laser scanning microscopy (CLSM) allowed localisation of the FITC-BSA near the surface of the microparticle. Microencapsulation of FITC-BSA did not altered the polymer characteristics, as determined by measuring the glass transition temperature. Additionally we could determine residual methylene chloride, employed as solvent in microparticle preparation, to be less than 1/1000 of the USP and Ph. Eur. limit. The microparticles described herein were able to deliver the model antigen to human dendritic cells (DC).     

Seasonal variations in the biophysical properties of rabbit aorta and its susceptibility to arteriosclerosis.

The physiological variations in the mechanical properties of rabbit aortae in relation to the periods of hair shedding were studied. The load-strain curves of the eight proximal thoracic segment in 15 shedding and 15 non-shedding male albino rabbits were analysed. The slope of the curves (tangent of the angle between the linear region of the load-strain curve and the strain axis) was decreased in the shedding animals compared to that of the non-shedding animals and the toe of the load-strain curves was significantly lower towards the x-axis in the shedding animals. The observations indicate a lower stiffness, that is increased elasticity, of the aortae of rabbits during hair shedding. The increased elasticity during hair shedding may explain the previously reported resistance to experimental arteriosclerosis caused by the hemodynamic strain elicited by exposure to systemic hypoxia. A decrease in the aortic content of collagen and of sulfated glycosaminoglycans, and an increase in the content of hyaluronic acid, may be of importance in the alterations of the mechanical properties of rabbit aorta during hair shedding.     

pH effect on osmotic response of collecting tubules to vasopressin and 8-CPT-cAMP

The effect of peritubular and luminal pH changes on hydraulic conductance, (Lp, 10(-7) cm X s-1 X atm-1) in the isolated perfused rabbit cortical collecting tubule (CCT) was tested at 37 degrees C before and after administration of 20 microU/ml vasopressin or 10(-4) M 8-[p-chlorophenylthio]-adenosine cyclic monophosphate (8-CPT-cAMP). In vasopressin experiments when bath pH was changed from 7.58 to 7.16 or from 7.58 to 6.70, mean Lp decreased from 249 +/- 32 to 199 +/- 23 (n = 5; P less than 0.01) and from 231 +/- 38 to 201 +/- 36 (n = 5; NS), respectively. In contrast, in 8-CPT-cAMP experiments when bath [HCO3] was kept constant while CO2 was elevated the hydroosmotic response was increased. Using 2.5 mM HCO3, Lp at 0.4% CO2 was 275 +/- 15 and at 6% CO2 it was 352 +/- 50 (n = 4; paired t test; P less than 0.05). At 8.5 and 21.5 mM HCO3 raising CO2 from 2 to 13% and from 4 to 32% increased Lp from 237 +/- 71 to 410 +/- 32 (n = 4; paired t test; P less than 0.05) and from 282 +/- 45 to 449 +/- 63 (n = 6; paired t test; P less than 0.001), respectively. Reducing luminal pH from 7.40 to 5.40 had no effect on either vasopressin- or cAMP-induced changes in Lp. Accordingly, lowering the bath pH by increasing the PCO2 at constant [HCO3] markedly stimulates the response to 8-CPT-cAMP, whereas lowering the bath pH by reducing [HCO3] inhibits the vasopressin response.