Superhydrophobic polypyrene films to prevent Staphylococcus aureus and Pseudomonas aeruginosa biofilm adhesion on surfaces: high efficiency deciphered by fluorescence microscopy.

A blue luminescent and superhydrophobic coating based on an electropolymerized fluorinated-pyrene monomer and its planktonic bacteria and biofilm repellent properties are reported. Two different pathogenic bacterial strains (Gram-positive and Gram-negative) at two different incubation times (2 h planktonic bacterial and 24 h biofilm adhesion) were studied and monitored (analyzed) using multicolor scanning confocal fluorescence microscopy. The coating was proved to reduce bacterial adhesion by 65%. It is highly effective against biofilm attachment, with 90% reduction of bacteria surface coverage. This blue fluorescent surface provides a facile method to characterize the coating, observe the bacterial distribution and quantify the bacterial coverage rate by fluorescence imaging of different colors. Furthermore, the film does not show significant bacterial toxicity during the working incubation times.

3D shapes of aryl(dihydro)naphthothiophenes: a comprehensive and structural study.

Convenient access to new aryl(dihydro)naphthothiophenes is described using a common ß-chloroacrolein derivative. Our strategy is based on the construction of a condensed thiophene ring prior to a Suzuki-Miyaura coupling and allowed installing various substituents at the molecular platform. The overall shapes of these architectures were confirmed by X-ray analyses and were in good agreement with theoretical calculations. It has been established that the relative orientation between all fragments that composed molecules within this series is strongly related to both steric and electronic factors. Contribution of these key parameters revealed to be crucial to rationalize attempts to prepare fluorenone and fluorene derivatives from aryl(dihydro)naphthothiophene platforms.

Understand, elucidate and rationalize the coordination mode of pyrimidylmethylamines: an intertwined study combining NMR and DFT methods.

Conception of new pyrimidylmethylamine (pyrma) ligands and their corresponding Pd(II) complexes has been described. Both symmetrical and non-symmetrical ligands were prepared and subjected to complexation. Two different coordination modes, Pd(N,N)- or Pd(C,N,N)-pyrma, have been evidenced depending on the substitution of the pyrimidine ring and the nature or the shape of the additional pendant arm. In a non-symmetrical pyrimidine series, the substituent-induced discrimination of each heterocyclic nitrogen atom provoked regio-controlled coordination to the metal center. The molecular structure of pyrma-Pd(II) complexes in the solution state has been elucidated thanks to combined NMR experiments and DFT calculations. This study highlights the potency of (15)N and (13)C NMR spectroscopy for the elucidation of the regio-selective coordination to the Pd(II) in the pyrma-based complex series. DFT calculations were highly relevant to the identification of crucial factors that govern the regio-selectivity and the complexation modes. Close predicted and experimental chemical shift values put into relief the reliability of coordination modes for the most stable complexes in solution, depicted by DFT approaches.

Accuracy of respiratory rate monitoring by capnometry using the Capnomask(R) in extubated patients receiving supplemental oxygen after surgery.

BACKGROUND: Respiratory monitoring is standard after anaesthesia and surgery. Abnormal respiratory rate is a sensitive indicator of respiratory problems, even in patients receiving supplemental oxygen, but the best method for its continuous measurement in spontaneously breathing patients is unclear. This study compared respiratory rate assessment by capnometry using a new oxygen mask with a carbon dioxide sampling port (Capnomask(®)) and thoracic impedance pneumography with clinical measurement (used as a reference method) in extubated patients receiving supplemental oxygen. METHODS: Adult males admitted to the post-anaesthesia care unit after general anaesthesia were studied. Immediately after extubation, a Capnomask(®) connected to a capnometer was positioned appropriately. Respiratory rate was measured by visual inspection of chest movement for 1 min, by capnometry, and thoracic impedance pneumography. One set of measurements was obtained for every patient receiving supplemental oxygen at different flow rates. RESULTS: Twenty men, mean (inter-quartile range) age 54 (23-66) yr and BMI 25 (21-31) kg m(-2), were studied. Compared with visual inspection, the bias and limits of agreement were 0.0 (1.0 to -1.0) bpm for the Capnomask(®) and -2.2 (2.0 to -6.5) bpm for the impedance pneumography. The accuracy of respiratory rate assessment using Capnomask(®) was not influenced by the supplemental oxygen flow rate. CONCLUSIONS: In extubated patients, continuous assessment of respiratory rate with the Capnomask(®) is more accurate than by thoracic impedance pneumography even when supplemental oxygen is delivered at a high flow rate.

Accuracy of respiratory rate monitoring using a non-invasive acoustic method after general anaesthesia.

BACKGROUND: Respiratory rate should be monitored continuously in the post-anaesthesia care unit (PACU) to avoid any delay in the detection of respiratory depression. Capnometry is the standard of care but in extubated patients requires a nasal cannula or a face mask that may be poorly tolerated or can be dislodged, leading to errors in data acquisition and false alarms. The value of a new non-invasive acoustic monitor in this setting has not been fully investigated. METHODS: Adult patients admitted to the PACU after general anaesthesia were included. After tracheal extubation, an adhesive sensor with an integrated acoustic transducer (RRa™) was placed on the patient's throat and connected to its monitor while the patient breathed through a face mask with a carbon dioxide sampling port (Capnomask™) connected to a capnometer. Both the acoustic monitor and the capnometer were connected to a computer to record one pair of data per second for up to 60 min. RESULTS: Fifty-two patients, mean (range) age 54 (22-84) yr and BMI 26 (19-39) kg m(-2), were studied. Compared with capnometry, the bias and limits of agreement of the acoustic method were 0 (-1.4-1.4) bpm. The acoustic sensor was well tolerated while the face mask was removed by eight patients, leading to study discontinuation in two patients. CONCLUSIONS: In extubated patients, continuous assessment of respiration rate with an acoustic monitor correlated well with capnometry.

Total and free ketoprofen in serum and synovial fluid after intramuscular injection.

Free and total ketoprofen levels in serum and synovial fluid were determined in 37 patients after a single intramuscular injection of ketoprofen, 100 mg. Free drug was separated by equilibrium dialysis. Ketoprofen was assayed by HPLC. Ketoprofen penetrated into the joints rapidly and significant concentrations were found at 15 minutes. The equilibrium time was about 3 1/2 hours. The AUC for total ketoprofen was greater in serum than in synovial fluid. On the other hand, the free fraction AUC in the serum and synovial fluid were quite similar. The mean residence time in the joint was about three times that in the systemic circulation. Ketoprofen was strongly bound to proteins and the percentage of free ketoprofen was not significantly different between serum and synovial fluid. These results provide a possible explanation for duration of the therapeutic effect of ketoprofen despite the short elimination half-life from the serum.

Articular diffusion of meloxicam after a single oral dose: relationship to cyclo-oxygenase inhibition in synovial cells.

OBJECTIVE: To investigate the distribution of meloxicam in the human knee joint and to compare it with the inhibition of cyclo-oxygenase (COX) activity in synovial cells. DESIGN: Prospective pharmacokinetic study and in vitro laboratory investigation. PATIENTS AND PARTICIPANTS: 42 male and female patients aged 26 to 85 years hospitalised for rheumatic disease and requiring a diagnostic and/or therapeutic knee puncture. METHODS: After a single oral dose of meloxicam 15mg, synovial fluid and blood samples were collected once per patient at various intervals after administration. Meloxicam concentrations were determined by a validated high performance liquid chromatography assay, protein binding by equilibrium dialysis, and pharmacokinetic parameters were calculated by noncompartmental analysis from the mean drug concentration-time profiles. The inhibitory effect of meloxicam on COX activity was investigated separately in unstimulated or interleukin-1beta-stimulated human synovial cells from osteoarthritic patients. RESULTS: Meloxicam was found in synovial fluid at the earliest sampling time (1 hour). Peak concentrations were reached approximately 6 hours postdose in both plasma (842 microg/L) and synovial fluid (320 microg/L). A plateau was observed after the distribution phase (6 hours), corresponding to a constant ratio of drug concentration between synovial fluid and plasma of about 0.47. This ratio was higher in patients with acute inflammation (0.58) than in those with no inflammation (0.38). Meloxicam was extensively bound to protein, mainly to serum albumin. The area under the drug concentration-time curve (AUC) in plasma was more than 2.5 times that in synovial fluid. The AUC for free meloxicam was similar in plasma and synovial fluid. The 50% inhibitory concentrations (IC50) for basal and stimulated COX activity in human synovial cells were 33.7 nmol/L (11.8 microg/L) and 2.0 nmol/L (0.70 microg/L), respectively. The free concentration of meloxicam in synovial fluid was higher than the IC50 for stimulated COX activity from 6 to 36 hours postdose. CONCLUSION: On the basis of free synovial concentrations and the IC50 for stimulated COX activity, meloxicam is expected to have a long duration of action. Inhibition of COX activity is expected to be more marked in inflamed synovium compared with non-inflamed synovium.

High-performance liquid chromatographic separation of novel atropic alpha,alpha-disubstituted-beta-amino acids, either on different beta-cyclodextrin-bonded phases or as their 1-fluoro-2,4-dinitrophenyl-5-L-alanine amide derivatives.

The high-performance liquid chromatographic enantioresolution of free and N- and/or C-protected derivatives of (R,S)-2',1':1,2;1",2":3,4-dinaphthcyclohepta-1,3-diene-6-aminometh yl-6- carboxylic acid (beta 2-Bin) by direct and indirect methods is reported. The direct separation was carried out on native and different derivatized beta-cyclodextrin-bonded phases. The indirect resolution was achieved by applying pre-column derivatization with 1-fluoro-2,4-dinitrophenyl-5-L-alanine amide. The effects of different parameters such as the mobile phase composition and the structures of the compounds on the enantiomeric resolution are discussed.

Influence of sulfasalazine on established collagen arthritis in rats.

Collagen induced arthritis (CIA) in rats is an experimental model that is characterized by an erosive synovitis associated with periostitis and both peripheral and axial ossifying enthesopathy. The influence of long-term therapy with sulfasalazine (80 mg/day on weekdays) on established CIA in Wistar Furth rats was investigated. Clinical and X-ray examination showed a significant improvement in the joint lesions of the uninjected paws in the treated rats as compared to controls. This effect was, however, delayed. On the other hand, periosteal new bone formation and caudal enthesopathy (spondylodiscitis) were not altered by the treatment.

Lymphocyte subpopulations in an experimental model of axial and peripheral enthesiopathies.

We report a study of lymphocyte subsets in experimental arthritis induced in Wistar Furth rats by native human type II collagen and muramyl dipeptide. This experimental arthritis shares similarities with both the spondyloarthropathies and rheumatoid arthritis. Peripheral blood T lymphocytes, primarily the CD4+ cells (p = 0.01), were lower in arthritic rats than in the controls, although the difference in the CD4/CD8 ratio was not statistically significant. Splenic CD4 cells were significantly (p = 0.03) more numerous in arthritic rats, while the numbers of MHC class II positive cells (p = 0.002) and kappa-bearing B-cells (p = 0.0004) were significantly lower. Determination of peripheral blood and spleen lymphocytes subsets could therefore be used for the assessment of arthritis and for the evaluation of therapeutic agents. Thymic T-cell differentiation does not appear to be impaired in this model. These results differ from the peripheral blood disturbances described in the active stages of human rheumatoid arthritis and are more similar to those reported in ankylosing spondylitis patients. However, the absence of alterations in the Peyer's patches suggests that pathogeneic mechanisms involving mucosal areas and exogenous intestinal antigens are not reproduced in this model.

Clinical pharmacokinetics of nonsteroidal anti-inflammatory drugs in the cerebrospinal fluid.

The pharmacokinetics of nonsteroidal anti-inflammatory drugs (NSAIDs) in the cerebrospinal fluid (CSF) is of clinical interest as it may be related to some of their properties and side-effects. Two types of NSAIDs can be described with respect to their concentration and time course in CSF: in the first type, the transfer across the blood-brain barrier seems to be controlled by simple physico-chemical factors. These drugs (oxyphenbutazone, indomethacin, ketoprofen) are characterized by a high lipophilicity. At steady state, their free plasma concentrations correspond to their CSF concentrations. The second group consists of more hydrophilic compounds (salicylates); there is no correlation between plasma concentrations and CSF concentration. Further investigation needs to be carried out on CNS side-effects and the antialgesic activity of salicylates in relation on their CSF distribution.

Experimental synovitis induced by aluminium phosphate in rabbits. Comparison of the changes produced in synovial tissue and in articular cartilage by aluminium phosphate, carrageenin, calcium hydrogen phosphate dihydrate, and natural diamond powder.

The goal of this experimental study was to examine the effect on articular tissue of tribasic aluminium phosphate (crystalline and amorphous forms) after intraarticular injection in rabbit and to compare it with that of various phlogistic compounds such as carrageenin, calcium hydrogen phosphate dihydrate and diamond powder, as a control. Synovium and cartilage were studied with light microscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy dispersive micro-analysis (EDM). Crystalline and amorphous aluminium phosphate could induce a synovitis with articular effusion in rabbits. With TEM, lysosomal inclusions of phagocytosed material were observed. Through SEM coupled with EDM, aluminium associated with phosphate was found in cellular elements.

Difficulties in applying the Scatchard model of ligand binding to proteins--proposal of new mathematical tools--application to salicylates.

Ill-considered use of the Scatchard model often leads to unjustified deductions. Since the main difficulty of this model is its number of parameters, new models are proposed that have only two parameters. After checking the models on simulated data, they were applied to real data on the binding of salicylates to albumin.

Piroxicam concentrations in plasma and synovial fluid after a single dose of piroxicam-beta-cyclodextrin.

AIMS: The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in rheumatic diseases depends on their concentrations within the joint. We determined piroxicam concentrations in plasma and synovial fluid (SF) after a single oral dose of 20 mg in the form of one tablet of piroxicam-beta-cyclodextrin. METHODS: 45 patients, aged 21 to 84 years, presenting with an effusion of the knee, related to degenerative or inflammatory joint disease, were included in this study after having given their written consent. One blood and one SF sample were drawn concomitantly in each patient from 0.5 to 48 h after NSAID administration. Piroxicam assays were performed by high performance liquid chromatography. Pharmacokinetic parameters were obtained from the mean plasma and synovial concentrations measured at various sampling times. RESULTS: The peak concentration was higher in plasma (2.51+/-0.25 microg/ml) than in SF (1.31+/-0.76 microg/ml), but the elimination half-life was much longer in SF (90.7 h) than in plasma (32.5 h). The SF/plasma area under the concentration-time curve ratio (evaluating the quantity of NSAID transferred from the blood to the joint) was equal to 0.39. CONCLUSIONS: Piroxicam contained in piroxicam-beta-cyclodextrin diffused well into the SF where its pharmacokinetic profile corresponded to that of a long half-life NSAID.

The 'small-patella' syndrome. Hereditary osteodysplasia of the knee, pelvis and foot.

We describe a syndrome combining abnormalities of the pelvis, knee and foot in three related patients with a familial history of small dislocated patellae. The clinical and radiological appearance of the patella and pelvis is consistent with the 'small-patella' syndrome, a rare autosomal dominant disorder. There were also previously unreported deformities affecting the feet.

Insufficiency fractures of the pelvis.

There are two kinds of stress fracture. One is fatigue fracture of a healthy bone during unusual mechanical overloading. This kind is seen particularly in young persons, such as soldiers and athletes, and most often affects the metatarsals, calcaneum, tibia, and fibula. The second kind is insufficiency fracture, in which the bone has become fragile because of age, metabolic disorder, static disorder of a leg, or prior orthopedic surgery, and cannot withstand even moderate stress. This type of fracture particularly affects the elderly, and is by far most frequent in the pelvis. Bone imaging is very helpful in early diagnosis of stress fractures, because as soon as there are clinical signs it reveals some degree of very localized uptake.

Radionuclide imaging in hip abnormalities.

The uptake of Tc-99m-diphosphonate was studied topographically and quantitatively on 258 diseased hips. For many diseased hips, bone scintigraphy provides items of information that complement the clinical, radiological, and biological data, with which it should always be compared. The localization, extent, and intensity of the uptake differ greatly according to the hip disorder studied, and depend not only on the cause of the lesion but also on its stage of evolution. Bone scintigraphy can shed light on the etiologic diagnosis of a painful hip at the beginning of its evolution, before definite roentgenographic signs appear, thanks to some very precise characteristics of the uptake, this is the case for transient osteoporosis of the hip, aseptic osteonecrosis, Legg-Perthes disease, early arthritis of the hip joint, and stress fractures of the femoral neck or of the pubic rami.

Parturition and angioneurotic oedema.

Angioneurotic oedema is a rare disease caused by Cl esterase inhibitor deficiency. Hereditary angioneurotic oedema includes type I (quantitative and functional) deficiency and type 11 (functional) deficiency. Its prophylactic treatment during pregnancy, based on danazol therapy if the fetus is male, may avoid acute attacks of generalized or laryngeal oedema. It must be instituted before delivery and carried into the postpartum period. If the fetus is female, epsilon aminocaproic acid may be used. The acquired form of angioneurotic oedema can be due to antibodies to C1 esterase inhibitor. A prophylactic therapy is not well established, but high doses of corticosteroids are recommended. Operative delivery is best avoided when possible. Regional analgesia is indicated for labour or caesarean section to prevent pain and stress and to avoid the difficulties associated with laryngeal oedema and tracheal intubation. In the treatment of an acute attack, Cl esterase inhibitor concentrates (1500 units) may be given i.v. We present two cases, one of hereditary and one of acquired angioneurotic oedema, both presenting during pregnancy and both delivered vaginally under epidural analgesia with successful outcome.

Decrease of in vitro serum protein binding of salicylate in rheumatoid arthritis.

Free and bound fractions of salicylates were separated by equilibrium dialysis and measured by spectrofluorimetry in 27 patients with rheumatoid arthritis and in 16 controls. The results showed that in patients with rheumatoid arthritis, the binding of salicylate to proteins decreased in an overproportional manner with the decrease of serum albumin concentrations. This phenomenon was linked with the severity of the inflammatory syndrome. The saturation binding capacity per unit of protein concentration was lower in the patients suffering from active forms of the condition, a finding which suggests that the changes observed are not due only to quantitative changes in the serum albumins. This study confirms the importance of determining free salicylate concentrations in the treatment of patients with inflammatory diseases.

[Sternocostoclavicular hyperostosis. Nosological concepts]. / Les hyperostoses sterno-costo-claviculaires. Conceptions nosologiques.

The term sternocostoclavicular hyperostosis groups affections of different pathogenicity. These result from an ossifying enthesiopathy, either inflammatory, isolated to the thoracic wall anteriorly or combined with a spondylarthropathy, particularly ankylosing spondylitis, or degenerative, the anterior thoracic hyperostosis usually being part of an ensheathing vertebral hyperostosis. A differential diagnosis is anterior thoracic hyperostosis due to an inflammatory osteopathy occurring in young patients and often associated with other bone lesions of pelvis and spine or long bones.