Biomedical subjects
Publications and source records attributed to D Baron.
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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.
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.
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.
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.
Elderly patients who develop insufficiency fractures of the sacrum usually have generalized bone loss and/or lesions of the pelvic bones (due to radiation therapy or previous fractures). The sacral fracture occurs either spontaneously or after a trivial traumatic episode. We compared patients admitted for sacral fractures (n = 12) or vertebral crush fractures (n = 56) in an effort to identify risk factors for sacral fractures. We conducted a retrospective review of the medical records of the 12 patients older than 70 years who were admitted to the rheumatology department of the Morvan Hospital between January 1, 1985 and December 31, 1994 for evaluation of a sacral fracture. The onset of symptoms was abrupt in 11 patients and occurred after an unremarkable fall in three. Patients admitted for sacral fractures were significantly more likely to have a positive history for a fracture, femoral surgery, or pelvic radiation therapy than patients admitted for vertebral fractures (58% versus 9%, p = 0.0005). In contrast, levels of calcium, phosphorus, 25-OH vitamin D and 1,25(OH)2 vitamin D were comparable in the two groups after exclusion of those patients with endocrine disorders or a history of calcium and vitamin D supplementation. In conclusion, populations of elderly patients with sacral fractures and crush fractures are comparable and the occurrence of a sacral fracture is dependent on the presence of pelvic and/or femoral osseous abnormalities.
Hereditary nonpolyposis colorectal cancer (HNPCC) is a genetic disorder characterized by a strong family history of colorectal and extracolonic cancers, usually at a young age. This article presents a new provincial service for families with HNPCC. The Steve Atanas Stavro Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital is accruing patients that meet a set of criteria establishing a putative diagnosis of HNPCC. The objectives of the Registry are to develop and assess patient pedigrees, to coordinate screening procedures for at-risk persons, to maintain a prospective database of patient information, to provide education and support for families and to contribute to research. To date, surgeons and patients are the most common referral sources, while oncologists and geneticists are the least common. The ultimate goal of the HNPCC service is the secondary prevention of cancer and a corresponding decrease in mortality for HNPCC family members.
Two synthetic fragments, corresponding to the 4-9 and 4-14 sequences of a tetradecapeptide used as a model to test the RXVRG-endoprotease activity from Xenopus laevis skin, have been studied by two-dimensional nmr spectroscopies, correlated spectroscopy, and nuclear Overhauser effect (NOE) spectroscopy. Both peptides wore the 5-9 consensus sequence found in several hormonal precursors. The nmr data for the 4-9 hexapeptide did not indicate any particular organization, either in water or in dimethylsulfoxide (DMSO), whereas, the 4-14 undecapeptide, a substrate for the RXVRG endoprotease, showed, in DMSO solution, significant trends of structural organization involving the amino acids pertaining to the consensus domain. From variations of integrated NOE peaks with temperature, the apparent interproton correlation times tau c were estimated and the maxima observed with Val7, the central residue in the consensus sequence. A defined tertiary structure in that domain was also supported by medium- and long-range NOEs between Asp6 and Arg8, Glu4 and Gly9, and by the likely involvement of Arg8 and Gly9 NHs in intramolecular hydrogen bonds. Most of these observations could be rationalized by an equilibrium between a 5-8 beta-turn and a 9 > 4 H-bonded loop. The predominance of one rotamer for the C alpha-C beta bond was established in four residues. Finally, the average phi and psi angles were derived from two models taking, or not, into account variations in the correlation times along the sequence. This allowed us to discuss the artefacts generated by using an average correlation time through the whole molecule.
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Capreomycin was incorporated into multilamellar vesicles of pure dipalmitoylphosphatidylcholine. The pharmacokinetics and nephrotoxicity of capreomycin in the free and liposomal forms were studied in normal mice. The efficacies of the two forms were evaluated by using the Mycobacterium avium complex beige mouse model. Approximately 10(7) viable M. avium cells were injected intravenously. Seven days later, treatment with either liposomal or free capreomycin at 60 or 120 mg/kg of body weight was administered daily for 5 days. Mice were sacrificed 5 days after the end of treatment, and the viable bacteria in liver, spleen, lungs, and blood were counted. After 5 days of treatment with dosages of 60 or 120 mg/kg/day, the level of blood urea nitrogen increased in the group treated with free capreomycin but not in the group treated with liposomal capreomycin. After intravenous injection of 120 mg/kg, liposomes enhanced the diffusion of capreomycin in the spleen, lungs, and kidneys and increased the half-life in serum. The 120-mg/kg dose of liposomal capreomycin significantly reduced the number of viable mycobacteria in the liver, spleen, and blood compared with those in the controls. Although these results are promising, further studies are needed to assess the efficacy of liposomal capreomycin for the treatment of M. avium complex infections.
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A patient who received treatment for acute myelogenous leukemia (chemotherapy, irradiation, corticosteroid therapy) developed cerebral radionecrosis with hemiplegia (treated by corticosteroids) then multiple foci of osteonecrosis on the nonparalyzed side. The mechanisms which may have prevented osteonecrosis from occurring on the side of the hemiplegia are discussed.
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Excessive intake of ethyl alcohol leads to acute intoxication and necessitates the same management as other forms of intoxication. Diagnosis is based on clinical examination, medical history and course. Determination of alcohol level in the expired air is of limited interest. If low or absent, it should direct clinical investigation toward a disorder having similar symptoms; if high, it does not necessarily explain the clinical picture. The severity of the intoxication must always be assessed carefully. Severity is linked either to a complication of acute alcohol intoxication (coma, inhalation, pneumopathy), or to an associated disorder, observed in 50% of the patients (cranial trauma, drug intoxication). Means of treatment and patient management are simple and well established.
Deltorphin-I, H-Tyr-(D)ala-Phe-Asp-Val-Val-Gly-NH2 and dermenkephalin, H-Tyr-(D)met-Phe-His-Leu-Met-Asp-NH2 are 2 members of small but growing family of D-amino acid containing opioid peptides isolated from the frog skin. Both peptides exhibit high affinity and selectivity for the delta-opioid receptor. Two-dimensional NMR study of deltorphin-I in DMSO-d6 revealed a close conformational homology with dermenkephalin. However, the temperature dependency of NOE correlations issued from Val5 and Val6 of deltorphin-I reflects a high intrinsic flexibility of the carboxyend. Whereas most of the JN alpha coupling constants and interresidue alpha N NOE effects were compatible with an extended structure, some sequential NOEs together with several medium and long range correlations involving Tyr1, Val6 and Asp4 may reflect an equilibrium mixture of extended and folded conformers in which the C- and the N-terminal parts of deltorphin-I are in close proximity. Finally, g- is the preferential conformer in the side chain of Phe3 in both deltorphin-I and dermenkephalin.
Dermenkephalin, H-Tyr-(D)Met-Phe-His-Leu-Met-Asp-NH2, a highly potent and selective delta-opioid peptide isolated from frog skin, was studied in DMSO-d6 solution by two-dimensional nmr spectroscopy, including the determination of NH temperature coefficients, the evaluation of 3J coupling constants from phase-sensitive correlated spectroscopy (COSY) and the volumes of nuclear Overhauser effect (NOE) correlations. The two-dimensional NOE spectroscopy (NOESY) spectrum of dermenkephalin revealed sequential, medium-, and long-range effects. To put this information on a quantitative basis, special attention was devoted to J cross-peak suppression, quantification of the NOE volumes and analysis of the overlaps, normalization of the NOEs against diagonal peaks and H beta beta' geminal interactions. Although most of the dihedral angles deduced from the 3JN alpha coupling constants together with several Ni alpha i and alpha iNi+1 NOEs pointed to a partially extended peptide backbone, several NiNi+1 NOEs and beta iNi+1 interactions argued in favor of a folded structure. Moreover, several long-range correlations of strong intensities were found that supported a close spatial proximity between the side chains of D-Met2 and Met6, Tyr1 and His4, Tyr1 and Asp7, and His4 and the C-terminal amide group. In Phe, the g- rotamer in the side chain is deduced from the 3J alpha beta coupling constants and alpha beta and N beta NOE correlations. Whereas the amide proton dependency was not indicative of stable hydrogen bonds, the nonuniform values of the temperature coefficient may reflect an equilibrium mixture of folded and extended conformers. The overall data should provide realistic starting models for energy minimization and modelization studies.
Twenty-four patients with suspected infection (eight bone, 16 lung) were studied using monoclonal antibody BW250/183 which recognizes epitopes present on the surface of granulocytes. Bronchofibroscopic samples (microbiological studies and alveolar cell counts) were obtained from 14/16 patients with lung disease. Bronchofibroscopy isolated a micro-organism nine times. In two other cases, the diagnosis of infection was based on clinical course data. Infection was confirmed by surgical biopsy in the eight patients with bone pathology. Scans were performed 2 and 24 h after injection of 1 mg BW 250/183 labelled with 99Tcm. For lung disease, immunoscintigraphy was positive six times (five true positive, one false positive) and negative 10 times (six false negative, four true negative). Immunoscintigraphy was false negative when the lung infection was not systematized or no granulocytes were mobilized in the infectious site. Immunoscintigraphy was falsely positive when noninfectious lung disease mobilized granulocytes. It was positive in all patients with bone infection. Images recorded at 24 h had better sensitivity (five false negative) than those at 2 h (eight false negative).
Aminoglycosides are commonly used in the treatment of nosocomial pneumonia in association with beta-lactams. Unfortunately, penetration of intravenously administered aminoglycosides into the lung tissue remains low. In animal models, aerosolization of these drugs provides high lung concentrations and low serum levels. Three-hundred milligrams of tobramycin and 1 ml of 99mTc-DTPA were administered via a pneumatic nebulizer to five healthy volunteers and to five mechanically ventilated patients. Lung scintigraphy was then performed, and plasma and urine pharmacokinetics were studied. In a second group of patients undergoing thoracic surgery, 300 mg of tobramycin alone were administered in the same way; a fragment of healthy lung was then removed, and tobramycin was measured. In the first group, the scintigraphy showed radioactivity distribution in the whole lungs both in healthy volunteers and in ventilated patients. Urine samples contained 5.5% of the initial amount of tobramycin. The mean serum half-life of tobramycin was 8.96 h in healthy volunteers and 11.23 h in ventilated patients. In the second group, mean lung tissue concentrations were 5.5 and 3.61 micrograms/g, respectively, 4 and 12 h after nebulization, respectively. Aerosolization of tobramycin thus produced high lung concentrations and low serum levels.