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Biomedical subjects

D Baron

Publications and source records attributed to D Baron.

At least 37 records · Page 2Linked to original sources
PubMed1996

Raynaud's phenomenon in rheumatoid arthritis.

The aim of this study was to evaluate the prevalence of Raynaud's phenomenon in patients with rheumatoid arthritis (RA), and to relate this symptom to clinical, radiological and serological characteristics of the patients. All relevant information was retrospectively obtained from the standardized clinical records of 322 RA in-patients first admitted to the Rheumatology Unit of Brest University Medical School. Raynaud's phenomenon was found in 54 (17.2%) of 322 RA patients. There was no significant correlation between demographic, clinical or radiological characteristics. However, the subgroup of RA patients with Raynaud's phenomenon had a slightly higher prevalence of vasculitis than the subgroup without Raynaud's phenomenon. CRP level and C4 level were found to be lower in the former than in the latter group, whereas ESR and various serological findings (rheumatoid factor, antinuclear antibodies) were comparable in the two groups. We conclude that the prevalence of Raynaud's phenomenon is high in French RA in-patients, and that some clinical and biological abnormalities (vasculitis, low CRP level and low C4 level) suggest an association between Raynaud's phenomenon and vasculitis in a few cases, whereas this association might be fortuitous in the remainder.

Adult↗
PubMed1996

Folded conformations of the delta-selective opioid dermenkephalin with head-to-tail interactions. A simulated annealing study through NMR restraints.

Despite similar tripeptide N-termini, dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) and dermenkephalin (Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2), naturally occuring opioid peptides from frog skin, exhibit high affinity but contrasting selectivity for the mu- and delta-opioid receptors, respectively. Structure-activity relationship studies have shown that the N-terminal tripeptide, Tyr-D-Xaa-Phe (where Xaa is either Ala or Met), is necessary for binding with both the mu- and delta-receptors while the nature and/or the conformation of the C-terminus His-Leu-Met-Asp-NH2 of dermenkephalin are responsible for addressing the peptide to the delta-receptor. In order to examine the conformational characteristics that are related to the selectivity of dermenkephalin towards the delta-receptor, 50 NOE restraints (10 between non-adjacent residues), and 7 dihedral angles, derived from a two-dimensional 1H-NMR study of dermenkephalin in dimethyl sulfoxide, were used in simulated annealing and energy minimization procedures. Twenty-four resulting conformers (60% of the generated structures) with no severe distance restraint violation were pooled into seven groups and three related families. These 24 conformers show close proximity between the two methionine residues, S-shaped structures, mean planes of N-terminal and C-terminal moieties almost at right angles to each other, a C-terminus region above the plane of the N-terminal region and g- as preferential orientation in the side chain of Phe. Aside these similarities, families of conformers differ by the preferential orientation in the side chain of Tyr (t or g-) and proximity between Tyr and Asp, or Tyr and the C-terminus. In contrast to previous models, practically no beta-turn structures exist for dermenkephalin, most of the NH hydrogen bonds participating to gamma-turns. The possible relationship between the conformational characteristics of dermenkephalin and the delta-opioid receptor selectivity is discussed.

Animals↗
PubMed1996

Influence of pH on adaptive resistance of Pseudomonas aeruginosa to aminoglycosides and their postantibiotic effects.

Adaptive resistance to aminoglycosides in Pseudomonas aeruginosa and other gram-negative bacilli is usually induced by the initial exposure to the drug. We investigated the influence of pH on the adaptive resistance of a clinical P. aeruginosa strain to aminoglycosides in vitro and on their postantibiotic effects. For adaptive resistance, the first-exposure concentrations of both amikacin and netilmicin were one, two, four, and eight times the MIC of each drug and the second-exposure concentrations were two times the MIC of each drug. Adaptive resistance was greater and more prolonged with higher initial aminoglycoside concentrations, and the bactericidal effects of the aminoglycosides were concentration dependent at pH 7.4. At pH 6.5, the killing rates of amikacin and netilmicin were far lower than those observed at pH 7.4. At pH 5.5, amikacin and netilmicin exerted practically no bactericidal effect on the P. aeruginosa strain used. However, with media at pH 5.5 and 6.5, adaptive resistance of P. aeruginosa preexposed to amikacin and netilmicin was also clearly exhibited, with the degree of adaptive resistance depending on the bactericidal effects of both drugs on nonpreexposed controls. Maximal adaptive resistance occurred between 0 and 4 h after preexposure. The postantibiotic effects of amikacin and netilmicin against the P. aeruginosa strain were shown to be concentration dependent and were reduced at acidic pHs. No changes in outer and inner membrane proteins occurred during the adaptive-resistance interval.

Adaptation, Physiological↗
PubMed1996

In vivo antibacterial effects of simulated human serum profiles of once-daily versus thrice-daily dosing of amikacin in a Serratia marcescens endocarditis experimental model.

Once-daily dosage of aminoglycosides is currently under consideration. The lower toxicity of this regimen has been clearly established, but there are conflicting experimental and clinical data concerning its efficacy. It is inadvisable to optimize human therapy by extrapolation from experimental studies since animal and human pharmacokinetics differ. The simulation of human pharmacokinetics in experimental infectious models would seem to offer a more rational approach. We used computer-controlled infusion of amikacin at a variable flow rate to simulate human pharmacokinetics in a Serratia marcescens rabbit endocarditis model and to compare two therapeutic regimens (once-daily versus thrice-daily doses). The doses corresponded to simulations of 15 and 30 mg/kg of body weight per day in humans, and antibacterial activity was measured in vegetations (Veg) after 24 h of treatment. The results show that the dose corresponding to 15 mg/kg/day failed to produce a significant reduction of CFU (6.8 +/- 0.9 and 6.4 +/- 0.8 log10 CFU/g of Veg, respectively, for once-daily and thrice-daily doses versus 7.6 +/- 1.0 for controls). A significant reduction was observed only for the dose corresponding to 30 mg/kg/day in humans (5.2 +/- 1.5 and 5.4 +/- 1.1 log10 CFU/g of Veg, respectively, for the two regimens). With this model, the efficacy of amikacin was similar for both regimens after 24 h of treatment simulating human pharmacokinetics.

Amikacin↗
PubMed1996

Spondylarthropathy with distal joint involvement.

To study whether the presence of distal joint involvement in spondylarthropathy corresponds to a particular set of the disease, one hundred and twenty six patients with spondylarthropathy were included in a retrospective study. Two groups of patients were defined according to the presence or the absence of distal joint involvement and their clinical, radiological, and biological features were compared. The patients with distal joint involvement had a later onset of spondylarthropathy and showed higher levels of biological markers of inflammation in their peripheral blood. However, no great difference appeared between the two groups of patients. Spondylarthropathy with distal joint involvement cannot be separated from spondylarthropathy without distal joint involvement and appears to be the same disease.

Adult↗
PubMed1996

Four new cases of collagenous colitis with joint symptoms.

Collagenous colitis is characterized by chronic watery diarrhea and a greater than 10 micron-thick collagen deposit in the subepithelial layer of the colonic mucosa. Rheumatic and autoimmune diseases have been reported to occur in patients with collagenous colitis. In 1993, we managed four patients with collagenous colitis and joint diseases. One had rheumatoid arthritis, one had a spondylarthropathy and two had seronegative polyarthritis without joint destruction. Three patients had dryness of the eyes and/or mouth and two had Raynaud's phenomenon. These four cases and data from a literature review provide a basis for discussing possible links between collagenous colitis and a number of joint diseases. Although some anecdotal case-reports may reflect a chance association with inflammatory joint diseases, available evidence suggests that collagenous colitis may be a cause of enteropathic arthropathy. Recent data point to an abnormality in the differentiation of fibroblasts in the colonic mucosa, although the mechanism that initiates this abnormality remains unknown.

Adult↗
PubMed1996

Is collagenous colitis a new etiology of sicca syndrome?

We conducted a prospective cross-sectional study of seven patients with collagenous colitis to determine the clinical, immunologic and histologic features of sicca syndrome associated with this condition. Four patients reported dryness of the mouth and/or eyes. No laboratory evidence of autoimmune disease was found, except in one patient with ankylosing spondylitis. Collagenous infiltration of the salivary glands was quantified in each patient as the percentage of the total gland surface examined. Histologic studies of salivary glands demonstrated significantly more collagen in the group of patients with collagenous colitis than in the group of age-matched controls (30.52% versus 11.8%, p < 0.05). No inflammatory infiltrates were seen. Our data suggest that a common mechanism may underlie the various lesions found in patients with collagenous colitis. However, the mechanism that initiates the fibrotic process in the colon and salivary glands remains unknown.

Adult↗
PubMed1995

[Critical serum concentration of antibiotics. A therapeutic tool and means of comparative evaluation].

It is difficult to predict the clinical activity of antibiotics solely on the basis of in vitro data. Experimental models measuring the relationship between serum concentration and in vivo activity are essential for comparing the activity of different compounds currently available. The critical serum concentration can be used to compare the intrinsic activity of antibiotics on a given bacterial strain. When compared with the minimal inhibiting concentration measured in vitro, "activity loss" can be determined for each antibiotic placed in contact with bacteria in an infected tissue. The relevance of this therapeutic tool in comparison with other methods is discussed.

Animals↗
PubMed1995

Anti-Fc gamma receptor III autoantibody is associated with soluble receptor in rheumatoid arthritis serum and synovial fluid.

We sought to detect anti-Fc gamma receptor (Fc gamma R) autoantibodies and soluble Fc gamma R in the serum and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and to correlate these serological abnormalities to the polymorphonuclear cell (PMN) activation state. Paired samples of blood and SF were obtained from 33 RA patients as well as blood from 25 normal adults from SF from 20 non-RA patients. Anti-Fc gamma R autoantibodies were assessed by an enzyme-linked immunosorbent assay (ELISA) using recombinant human Fc gamma R as the substrate. Soluble Fc gamma RIII was determined by an ELISA based on the combination of two monoclonal antibodies (MAb). The mean fluorescence intensity (MFI) of complement receptor 1 (CD35) and 3 (CD11b) and Fc gamma RIII (CD16) was evaluated by flow cytometry on the membrane of PMN. IgM anti-Fc gamma RIII activity was present in seven RA sera and five SF, and IgG in eight RA sera and six SF. The average concentration of soluble Fc gamma RIII was 1.80 +/- 3.50 micrograms/ml in RA patients and 0.33 +/- 0.06 micrograms/ml in normal adults (P < 0.05). This was elevated in the SF of 15 RA, while normal in that of all the non-RA patients. There was an inverse correlation between the CD16 MFI on the PMN and the serum/SF soluble Fc gamma RIII level, whereas the density of CD35 and CD11b was markedly augmented. Anti-Fc gamma RIII activity exists in RA patients, associated with soluble Fc gamma RIII. PMN activation could be due to these autoantibodies and thereby obviate the clearance of immune complexes.

Adult↗
PubMed1995

Structure determination of a tetradecapeptide mimicking the RXVRG consensus sequence recognized by a Xenopus laevis skin endoprotease: an approach based on simulated annealing and 1H NMR.

The tetradecapeptide of sequence H-Asp-Val-Asp-Glu-Arg5-Asp-Val-Arg-Gly9-Phe-Ala-Ser-Phe-Leu- NH2 is recognized by a putative maturation endoprotease of the Xenopus laevis skin, which cleaves between Arg8 and Gly9. A conformational search has been performed on this peptide by simulated annealing calculations. Two different models in agreement with the NMR data were found. The conformational difference between the two types of model is located in the consensus sequence, i.e., from Arg5 to Gly9.

Amino Acid Sequence↗
PubMed1995

Two-dimensional 1H NMR study of a tetradecapeptide with the consensus sequence Arg5-Asp-Val-Arg-Gly9: structural effects of the outside substitution Ser12 by Ala12.

Conformation of a tetradecapeptide with a RXVRG consensus sequence, Arg5-Asp-Val-Arg-Gly9, found in several precursors of antibacterian peptides, was investigated in dimethylsulfoxide solution by proton NMR spectroscopy. Complete resonance assignments and conformational parameters were obtained through correlated (COSY) and nuclear Overhauser (NOESY) techniques. The 3J(alpha H, beta H) coupling constants and the intramolecular NOE, NH...beta H, were used to analyse the conformers around the C alpha-C beta bond and, in four cases, to obtain stereospecific assignments. Use of restraints derived from NOE connectivities and 3J(NH, alpha H) coupling constants allows the determination of a range of phi and psi dihedral angles for all the residues in the sequence. The present NMR results provide favourable evidence for the formation of two bends in the consensus sequence of the tetradecapeptide. The first one has most of the features of a Glu4-Val7 beta-turn (low temperature coefficient of the Val7NH chemical shift, Arg5 alpha H...Val7NH and Asp6NH...Val7NH NOE correlations). The second one exhibits only the Asp6 alpha H...Arg7NH and Val7NH...Arg8NH NOE interactions. These consensus sequence organizations proposed were confirmed by molecular modeling based on low potential energy structure on the [4-9] fragment with high agreement of NOE data. Overall, the substitution of Ser12 by Ala12 shifts the conformation of the hydrophobic moiety [10-14] towards a quite random coil structure in this fragment and strongly destabilizes the folded structures of the consensus domain where only one NH (Val7) is solvent-shielded opposed to three (Asp6 to Arg8) in the [Ser12] tetradecapeptide. These conformational changes could be related to the processing enzyme activities on these model oligopeptides.

Alanine↗
PubMed1995

The antiperinuclear factor in spondylarthropathies.

The aim of the present study was to evaluate the prevalence of antiperinuclear factor (APF) in patients with spondylarthropathy and the relationships between this autoantibody and a variety of clinical, radiological and serological findings. We conducted a retrospective review of the medical records of all patients first admitted to the Rheumatology Unit of the Brest University Medical School Hospital from 1 January 1986 to 31 December 1994, and who met the European Spondylarthropathy Study Group (ESSG) criteria at admission. Each patient had a standard battery of tests. Serum samples from 123 of 126 patients suffering from spondylarthropathy were examined for the presence of APF. Thirty-three patients (26.8%) had APF at a titre > or = 1/80. There were no significant relationships between various demographic, clinical or radiological characteristics and the presence of APF. However, the subgroup of APF-positive patients had a higher prevalence of both rheumatoid factors (RF), although not significant, and antikeratin antibody-positive serum than the rest. These results suggest that some patients had rheumatoid arthritis (RA) and three patients with APF > 1/100 and who were RF positive met ACR criteria for RA. APF should thus be used only as an additional serological marker in cases where clinical features suggest the association of spondylarthropathy with RA.

Adult↗
PubMed1995

NMR conformational study of a model tetradecapeptide mimicking the RXVRG consensus cleavage site of a Xenopus laevis skin endoprotease.

A model tetradecapeptide, used for the purification of the RXVRG-endoprotease from Xenopus laevis skin exudate, has been studied by two-dimensional NMR, correlation (COSY) and NOE (NOESY) spectroscopy. This peptide has the 5-9 consensus sequence (RXVRG), along with an acidic moiety (1-4) and a hydrophobic domain (10-14). Variations with temperature of NH chemical shifts in a dimethyl sulfoxide solution (low thermal coefficients at residues 6, 7 and 8) and quantified NOE values from four spectra at different mixing times clearly showed a structural organization in the consensus domain with psi-angles around [-40, -10 degrees] for residues 7 and 8, and two NOE correlations of alpha HiNHi + 2 type (5-7 and 6-8). Moreover, a privileged rotamer in the side chain is established for three residues (Val2, Asp3 and Val7) and limited possibilities are discussed for seven others. Most of the folding trends were not observed in the [Ser7] derivative, underlying the relationship between the conformations and a full consensus sequence. In the model tetradecapeptide an equilibrium between two beta-turns of type I, fragments 4-7 and 5-8, seems the most probable. Comparison between this tetradecapeptide and its 4-14 fragment, also a substrate for RXVRG-endoprotease, shows that the 1-3 moiety (DVD) influences the consensus domain structure(s) and clearly stabilizes the folded one(s). Finally, two analytical methods are developed in order to determine: (1) the trifluoroacetic acid content of the peptide samples, on the basis of 19F NMR spectroscopy; (2) the mean phi- and psi-angles of each residue, from the whole set of NH/alpha H coupling constants (3JN alpha) and NOE data at a local level.

Amino Acid Sequence↗
PubMed1995

Comparative efficacies of ciprofloxacin and pefloxacin alone or in combination with fosfomycin in experimental endocarditis induced by multidrug-susceptible and -resistant Pseudomonas aeruginosa.

The in vivo efficacy of ciprofloxacin or pefloxacin alone or in combination with fosfomycin was evaluated in experimental aortic valve endocarditis induced in 133 rabbits by a multidrug-susceptible or multidrug-resistant strain of Pseudomonas aeruginosa. Therapy was initiated early (12 h after infection), when bacterial counts in aortic valve vegetations were relatively low, or late (48 h after infection), when vegetations contained a larger inoculum. Antibodies were administered as a continuous 24-h intravenous infusion. Mean steady-state levels of ciprofloxacin (64 mg/kg), pefloxacin (64 mg/kg), and fosfomycin (300 mg/kg) in serum were 2.5, 4.2, and 63.9 mg/liter, respectively. For the multidrug-susceptible strain, all regimens except pefloxacin alone significantly reduced the number of CFU per gram of vegetation versus controls, whether treatment was performed early or late. For the multidrug-resistant strain, none of the regimens showed differences from untreated controls, except ciprofloxacin-fosfomycin, which significantly reduced bacterial counts in vegetations compared with controls when therapy was begun early (4.1 +/- 1.1 log10 CFU/g of vegetation; P < 0.001 versus the control). These data suggest that combination of fosfomycin with ciprofloxacin or pefloxacin is more effective than ciprofloxacin or pefloxacin alone for the therapy of severe infections caused by multidrug-susceptible P. aeruginosa.

Animals↗
PubMed1995

How useful are tests for rheumatoid factors, antiperinuclear factors, antikeratin antibody, and the HLA DR4 antigen for the diagnosis of rheumatoid arthritis?

To evaluate the usefulness for the diagnosis of rheumatoid arthritis of tests for rheumatoid factors, antiperinuclear factors, antikeratin antibodies, and the HLA DR4 antigen, we retrospectively reviewed the medical records of 138 patients consecutively admitted to our rheumatology department between January 1, 1988 and December 31, 1990 for evaluation of peripheral inflammatory joint manifestations. Each patient had a standard work-up including a physical examination, laboratory tests, and roentgenograms. In 1994, after a follow-up of three to six years, the final diagnosis was rheumatoid arthritis in 39 patients and another well-defined disorder in 63; no diagnosis was established in 36 patients, among whom nine were lost to follow-up. The decreasing order of diagnostic usefulness was antiperinuclear factors, HLA DR4, rheumatoid factors (latex test), and antikeratin antibody. The likelihood of rheumatoid arthritis was greatest in those patients with positivity of two of the three following markers: rheumatoid factors, antiperinuclear factors, and the HLA DR4 antigen.

Adult↗