F74 plasmids are major vectors of virulence genes in bovine NTEC2.

Necrotoxigenic Escherichia coli 2 (NTEC2) are defined as E. coli producing the toxin known as cytotoxic necrotizing factor 2 (CNF2), a potent toxin primarily found in bovine but also in humans. NTEC2 are mostly associated with bovine, and cnf2 is known to be carried by pVir-like plasmids. In this study, we looked for NTEC2 in a collection of E. coli collected between 2011 and 2018 in French bovine. Thirty-two isolates, collected from both sick (n = 19) and healthy (n = 13) animals, were identified and characterized using whole-genome sequencing. One F74 plasmid of this bacterial collection was long-read sequenced: its size was 138 121 bp and it carried the cnf2, F17cA-eG, cdtB, iutA, iucC and ompP virulence factors (VFs), but no resistance gene. A large variety of genetic backgrounds was observed, but all cnf2-carrying plasmids belonged to the IncF family, and most of them (78·1%) were of the F74 group. Similar F74 plasmids were also reported from bovine in the United Kingdom and the United States, as identified in the publically available databases. Consequently, these F74 plasmids, which are widely disseminated among E. coli from cattle in the French territory, are vectors of virulence determinants that largely went unnoticed until now.

Overall changes in the transcriptome of Escherichia coli O26:H11 induced by a subinhibitory concentration of ciprofloxacin.

AIMS: The goal was to explore the effects of subinhibitory concentration (SIC) (0·5 MIC = 20 µg l-1 ) of ciprofloxacin on the transcriptome of enterohaemorrhagic Escherichia coli O26:H11 isolate by 60 minutes of exposure. MATERIALS AND RESULTS: We used a combination of comparative genomic and transcriptomic (RNAseq) analyses. The whole genome of the E. coli O26:H11 #30934 strain of bovine origin was sequenced and assembled. This genome was next used as reference for the differential gene expression analysis. A whole-genome-based analysis of 36 publicly available E. coli O26:H11 genomes was performed to define the core and the accessory transcriptome of E. coli O26:H11. Using RNAseq and RT-qPCR analysis we observed overexpression of the SOS response and of T3SS effectors, together with the inhibition of specific motility-associated genes. Among the large set of transposases present, only three were activated, suggesting moderate transposition of genes with low doses of ciprofloxacin. Our results illustrated that transcriptional repressors, such as the CopG family protein, belonging to the core genome of E. coli O26:H11, are altered in response to fluoroquinolone exposure. The gene ontology enrichment analysis showed SIC of ciprofloxacin induced binding functions and catalytic activities, including mostly transferase and hydrolase proteins. The amino acid pathways involved in metabolic processes were significantly enhanced after the treatment. CONCLUSIONS: Although the core genome of E. coli O26:H11 constituted only 54·5% of the whole genome, we demonstrated that most differentially expressed genes were associated with the core genome of E. coli O26:H11, and that effects on the mobile genetic element, phage, and plasmid-related genes were rare. SIGNIFICANCE AND IMPACT OF THE STUDY: For the first time the effect of low dose of ciprofloxacin on the core transcriptome of E. coli O26:H11 was described. The effects on the main biological functions and protein classes including transcriptional regulators were illustrated.

Transfer of melamine in some poultry products.

This study deals with the transfer of melamine from poultry feed to certain poultry products, such as eggs and meat destined for human consumption. The tested amounts were, respectively, 50 and 500 mg of melamine/kg of feed. The addition of melamine had no significant effect on feed consumption and egg production. However, melamine appeared in the eggs as early as the first day of exposure. The average concentration was reached after the third day at both levels of contamination. The amounts of melamine found in eggs and tissues were almost directly proportional to the quantities ingested. However, melamine did not appear to accumulate in the organs and tissues that were studied.

[Assessment of the usefulness of autologous serum skin testing in chronic urticaria: a retrospective single-centre study of 74 patients]. / Evaluation de l'utilité du test au sérum autologue dans l'urticaire chronique idiopathique: étude rétrospective chez 74 patients.

BACKGROUND: Chronic urticaria (CU) is a debilitating disease, and patients and their physicians often seek an aetiological explanation. Studies have suggested that idiopathic CU is associated with the presence of serum auto-antibodies that may be detected by autologous serum skin test (ASST). AIM: To confirm the frequency of positivity of ASST and to evaluate its usefulness and possible correlation with the severity of urticaria (greater resistance to AH1, greater activity score or longer duration). PATIENTS AND METHODS: Patients referred for CU between 1 October 2001 and 31 March 2005 were submitted to standardized explorations including clinical examination, physical tests, CBC, ESR, CRP and anti-thyroperoxidase antibodies, and an ASST was ordered. Inclusion criteria included no discernible cause of CU, acceptance of the protocol, including blood sampling and injection of ASST 3 weeks later, serological tests for HBV, HCV and HIV, and discontinuation of anti-H1 agents and corticosteroids. Exclusion criteria comprised the presence of dermographism, physical urticaria, urticarial vasculitis, and failure to discontinue anti-H1 drugs or corticosteroids. In April 2006, we contacted patients by mail to assess their current treatment, their CU activity score or its resolution. RESULTS: Seventy-four patients (67 women, seven men) of mean age 43 years were included. ASST was positive in 43 patients (58 %) and negative in 31 (42 %). The only noticeable difference, although not statistically significant (p=0.23), was a positive anti-thyroperoxidase antibody result in 12 % of patients with negative ASST versus 24 % of patients with positive ASST. The occurrence of angioedema, the duration of CU, the severity score, the relative inefficiency of AH1 and the use of corticosteroids or cyclosporine were similar between the two groups. DISCUSSION: ASST was positive in more than half of the patients with idiopathic CU both in our study and in the literature, with sensitivity of around 70 % and specificity approaching 80 %. However, while this test can help patients understand their disease better and avoid both a fruitless search for other causes and unnecessary proscription of food allergens, our study shows that positive or negative ASST results have no bearing on treatment and are not associated with greater severity of urticaria or greater resistance to treatment. Consequently, we do not recommend routine use of ASST in patients presenting idiopathic CU.

Comparative analysis of different scintigraphic approaches to assess pulmonary ventilation.

A study was carried out to investigate the predictive value of 81-metastable-krypton (81mKr) distribution, high-size 99-metastable-technetium (99mTc) aerosol deposition and low-size 99mTc aerosol (Technegas) deposition on the pulmonary ventilation evaluated by 133-xenon (133Xe) lung scintigraphy, and to assess the correlation between the 81mKr distribution, the 99mTc aerosols deposition, and the respiratory parameters of patients with chronic obstructive pulmonary disease (COPD). Twenty COPD patients were included. The 81mKr, 133Xe, and 99mTc aerosol lung scintigraphies were successively carried out. The 81mKr distribution and 99mTc deposition were compared to the 133Xe distribution at equilibrium and to the 133Xe clearance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 81mKr and Technegas lung scintigraphies to detect alterations in ventilation revealed by 133Xe were defined. The 81mKr distribution and 99mTc deposition according to respiratory parameters were described using a principal component analysis. Compared to 133Xe distribution, a significantly higher distribution of 81mKr in the upper parts of the lungs in the more severe patients (p = 0.05), a significantly higher deposition of Technegas in the lower parts of the lungs (p = 0.0008), and a significantly higher deposition in the central parts of the high-size 99mTc aerosol were observed (p = 0.0001). The PPV and the NPV were, respectively, 0.54 and 0.58 for 81mKr and 0.54 and 0.55 for Technegas. There was a significant negative correlation between 81mKr distribution and 133Xe clearance (p = 0.0001) between Technegas deposition and 133Xe clearance (p = 0.0007), and between 99mTc diethylene-triamino-penta-acetate (DTPA) deposition and 133Xe clearance (p = 0.001). Both the 81mKr peripheral distribution and Technegas peripheral deposition correlated negatively with increased obstruction, as measured by forced expiratory volume in 1 sec (FEV1). Peripheral deposition of the high-size 99mTc aerosol deposition correlated with the inspiration/expiration time ratio. In conclusion, 81mKr and 99mTc aerosols' lung scintigraphies do not reflect exactly the pulmonary ventilation as measured by 133Xe scintigraphy.

Using bioluminescent biosensors for hazard analysis and critical control point (HACCP) in wastewater control.

Starting from a new approach for water pollution control and wastewater treatment plant management, the hazard analysis and critical control point (HACCP) quality concept, the interest for the development of new rapid and sensitive methods such as bioluminescence-based methods is evident. After an introduction of the HACCP procedure, a bibliographic study of the bioluminescence potentiality is presented and discussed.

Characteristics of EPI-hNE4 aerosol: a new elastase inhibitor for treatment of cystic fibrosis.

The purpose of this study was to define nebulization conditions providing delivery of aerosols of EPI-hNE4, an inhibitor of human neutrophil elastase (HNE). EPI-hNE4 was nebulized with Pari LC Star and tested at three concentrations (2.5, 5, and 10 mg/mL). The inhaled mass was measured over 15 min. Particle size distribution was measured by cascade impaction. The effect was also tested of mixing EPI-hNE4 with a (99m)Tc human serum albumin (HSA) tracer on the aerodynamic properties of the aerosol. The inhibitory activity of EPI-hNE4 after nebulization was assessed on purified HNE. The inhaled mass was 32.3 +/- 3.5% (mean +/- SD) after 10 min and 44.2 +/- 3.8% (mean +/- SD) after 15 min. Mass median aerodynamic diameter ranged between 1.2 and 1.8 microm. The (99m)Tc HSA EPI-hNE4 aerosol was similar in terms of particle size distribution (y = 1.0338x - 0.003, r = 0.83). (99m)Tc activity was predictive of EPI-hNE4 mass distribution (y = 1.0278x - 1.6991, r = 0.89). The inhibitory capacity of aerosolized samples remained unchanged after up to 10 min of nebulization. EPI-hNE4 can be nebulized efficiently without decrease in its activity. Mixing this inhibitor with (99m)Tc HSA should allow quantification of its deposition in CF patients.

Bioluminescence-based assay used for toxicity monitoring.

A new ATP bioluminescence-based method is proposed in order to examine the effect of toxic shock on microbial communities in urban wastewater treatment plant (WWTP). As the efficiency of WWTP must be improved, the occurrence and toxic effect of hazardous substances have to be evaluated (Directive 2455/2001/EC). Among bioluminescence assay with firefly luciferase is commonly used for intracellular ATP monitoring. A multienzyme systems catalysed by three enzymes (adenylate kinase, pyruvate kinase and firefly luciferase) for adenine nucleotides (AN = ATP+ ADP+ AMP) estimation is used for monitoring metabolic changes in activated sludge. The AN method provides better sensitivity than ATP quantification alone. The pool of intracellular and extracellular AN is constant during growth and the rate of intracellular AN is correlated with the microbial growth. In the present investigation, the extraction of total adenylate assay is optimized (chemical and mechanical extraction) and applied for monitoring the effect of the toxic shock (eg. Naphthalene) on indigenous biomass activity (intracellular and extracellular AN rates). In the same time, the removal of naphthalene is addressed Laboratory-scale reactors (4 L) are inoculated with urban activated sludge is under continuous-flow aeration. The reactor, containing non acclimated sludge enriched with naphthalene. The other reactor containing sterilised activated sludge is used as abiotic and volatilisation control system. In all this batch cultures, ATP and AN (intracellular and extracellular) rates and naphthalene concentrations are controlled. One of the objectives of this research is to determine a relation between the ATP/AN ratio and the biodegradation of naphthalene. Evidence is given which demonstrates that the ATP/AN parameter is a possible alternative for monitoring very rapid metabolic changes in complex microbial community such as activated sludge.

Urinary excretion reflects lung deposition of aminoglycoside aerosols in cystic fibrosis.

Using nebulization to deliver aminoglycosides may be of benefit in cystic fibrosis (CF) patients colonized by Pseudomonas aeruginosa. However, one problem with this route is the absence of clinical parameters allowing estimation of the mass of drug deposited in the lungs (MDL). The aim of this study was to assess whether aminoglycoside excretion in the urine reflects the MDL. Fourteen studies were performed in seven CF patients. Amikacin was mixed with albumin labelled with 99mTc and nebulized with an ultrasonic nebulizer. The MDL was determined by the mass-balance technique. Urine was collected during the 24 h following inhalation and was assayed for amikacin by fluorescence polarization immunoassay (FPIA). The mean+/-SEM MDL was 14.0+/-2.2% of the nebulizer charge. The mean+/-SEM amount of amikacin excreted in the urine was 20.9+/-4.5 mg and correlated with the MDL (r=0.93; p=0.0001). There was, however, wide intersubject variability in both deposition and excretion in the urine. Monitoring excretion of aminoglycosides in the urine allows noninvasive estimation of the mass of drug deposited in the lung in cystic fibrosis patients, which might be useful to assess the dose-response relationship in groups of patients, but intersubject variability prevents its use for individual follow-up.

Characterization of 99mTc-DTPA aerosols for lung permeability studies.

BACKGROUND: The interpretation of 99mTc diethylenetriamine pentaacetate (99mTc DTPA) aerosol clearance is based on the hypothesis that the 99mTc-DTPA complex is not altered by the nebulization process. OBJECTIVES: To characterize (1) the radiochemical purity (RCP) of 99mTc-DTPA and the stability of labeling after jet nebulization, and (2) the particle size distribution of the aerosol. METHODS: RCP and stability--the aerosol was driven by oxygen, captured on filters which were eluted and RCP was checked by thin layer chromatography. Particle size distribution--the aerosol was generated using dry air (50 psi) at three different flow rates, i.e. 3 (1 run), 6 (4 runs) and 9 l x min(-1) (4 runs). The mass median aerodynamic diameter (MMAD) and the geometric standard deviation (sigma(g)) were determined using a cascade impactor from the radioactivity counted on each stage. RESULTS: The RCP was more than 95% in all cases. Mean MMAD (+/-SD) was 0.70 microm (+/-0.07) at 9 l x min(-1), 0.93 microm (+/-0.05) at 6 l x min(-1) (p < 0.05) and 1.50 microm at 3 l x min(-1). Mean sigma(g) (+/-SD) was 2.02 (+/-0.08) at 9 l x min(-1), 2.00 (+/-0.16) at 6 l x min(-1) and 1.90 at 3 l x min(-1). CONCLUSION: This study demonstrates (1) that the high RCP of 99mTc-DTPA is not affected by jet nebulization, even when using oxygen at a high flow rate, and (2) that when using a flow rate between 6 and 9 l x min(-1), the MMAD remains optimal for peripheral lung deposition.

A new serologic index for low-grade non-Hodgkin's lymphoma based on initial CA125 and LDH serum levels.

BACKGROUND: Serum CA125 (sCA125) was recently reported to be of clinical value in the staging and follow-up of patients with non-Hodgkin's lymphoma (NHL). This report aims to investigate the prognostic value of a new serologic index combining sCA125 and LDH serum levels. PATIENTS AND METHODS: One hundred thirty-seven patients were studied, sixty-three with histologically proven low-grade NHL, and seventy-four with a high-grade subtype. RESULTS: sCA125 and LDH levels were elevated in more than one third of patients. sCA125 was more frequently increased than LDH in low-grade NHL. In this group, complete remission (CR) was achieved in 87, 45, and 0% (P = <2 x 10(-6)) of patients with normal sCA125 and LDH serum levels (Low-risk group), one parameter increased (Intermediate-risk group), and increased sCA125 and LDH serum levels (high-risk group), respectively. The estimated five-year overall survival was 97%, 67% and 22% for low, intermediate, and high-risk groups, respectively. This combination was the only parameter predictive of RFS and OS in multivariate analysis (P < 0.0001). CONCLUSIONS: In this study the combination of s-LDH and sCA125 levels (normal vs. abnormal) was found to be an important prognostic factor in low-grade lymphoma and may be used in the selection of appropriate therapeutic approaches for individual patients.

[Strategy for early diagnosis of lung involvement in systemic scleroderma]. / Stratégie pour le diagnostic précoce de l'atteinte pulmonaire dans la sclérodermie systémique.

Systemic sclerosis (SSc) is an autoimmune disorder characterized by accumulation of collagen in affected organs, mainly the skin and the lungs, associated with abnormalities of the arterioles and capillaries. There are two types of pulmonary involvement, which influence long term prognosis: infiltration of the lungs and/or pulmonary artery hypertension. Full investigations into possible lung involvement must be performed systematically when SSc is diagnosed and during follow-up. The double pathophysiology sometimes makes diagnosis difficult but it must be made as early as possible in order to decide on the optimal treatment. The aim of this study was to evaluate the usual explorations and to propose biological markers to identify patients requiring more detailed lung investigations, in order to establish a diagnostic approach to treatment and follow-up patients with SSc.

Severe non-infectious circulatory shock related to hypopituitarism.

The authors report a case of refractory non-infectious circulatory shock with catecholamine and massive fluid loading-resistant features related to hypopituitarism. A 76-year-old man was admitted for shock after suffering from gastroenteritis for 3 days. He was pale and had sparse axillary and pubic hair and small testes. Right catheterization showed shock with low preload pressure and a low oxygen extraction ratio relevant for septic shock. Ultrasound tomography revealed a distended gallbladder due to a stone without peritoneal effusion. A non-inflammatory hydrops of the gallbladder was removed surgically. No microorganism was isolated. Cerebral computed tomography (CT) scan showed a pituitary mass. In the post-surgical period the shock became uncontrollable. Cortisol replacement therapy was instituted and clinical and hemodynamic improvement occurred after 2 h. Hormonal screening on admission before catecholamine administration showed a major decrease in all the hypothalamic-pituitary hormone concentrations. The patient died on day 15 with multiple organ failure. Hypopituitarism, probably owing to pituitary adenoma, was the only disease identified in this case. Hormone replacement therapy dramatically improved the clinical and hemodynamic status, although the role of an abdominal sepsis could not be eliminated. Arguments that pituitary hormone deficiency might increase the hemodynamic consequences of adrenal deficiency are discussed.

[Serum procalcitonin and respiratory tract infections]. / Procalcitonine sérique et pathologie infectieuse respiratoire.

The aim of our study was to evaluate the prognostic value of serum procalcitonine (PCT) assay in adult respiratory infections. Forty-nine patients admitted with pleurisy, community-acquired pneumonia, tuberculosis, infection were included in this prospective study. PCT was assayed on admission and discharge. Biological and clinical parameters of gravity were also evaluated. Twenty patients had elevated PCT of more than 0.50 ng/ml. In 29 patients, PCT was undetectable. The serum PCT level was normal in the patients with tuberculosis, infection, pneumocytosis. PCT did not correlate with the biological and clinical markers of the disease severity but the evolution of PCT correlated with the evolution of C-reactive-protein (r = 0.58, p < 0.05). PCT seems to be an early marker of the evolution of respiratory infections, but it does not help to establish prognosis. Further studies are necessary to assess the potential value of PCT in more severe respiratory infections requiring assisted ventilation.

[Thyroid function and autoimmunity in 215 patients seropositive for the hepatitis C virus]. / Fonction et auto-immunité thyroïdienne chez 215 patients séropositifs pour le virus de l'hépatite C.

The aim of this study was to estimate thyroid function and the prevalence of thyroid antibodies among HCV seropositive patients. We undertook a screening for thyroid dysfunction, and antithyroperoxidase (ATPO) and antithyroglobulin (ATG) antibodies, in 215 HCV seropositive patients referred for hepatologic consultation, 118 males and 97 females, mean age 44 +/- 14 years, range 16-80 years. No patient was treated with interferon and all were seronegative for HIV. Eighteen patients (8%) had antithyroid antibodies, 12 with ATPO antibodies (5.6%) and 10 with ATG antibodies (4.7%). Four patients had both ATPO and ATG antibodies (1.8%), one case of Graves' disease and 3 cases of autoimmune hypothyroidism found during this study. Five patients (2.3%) had hyperthyroidism, three cases of Graves' disease, one case of iodine load and a case of Grave's disease incidentally diagnosed during medical examination. Eleven patients (5.1%) had hypothyroidism, one case already known and treated without antithyroid antibodies, 4 cases of autoimmune etiology (3 diagnosed in consultation and one already known and compensated hypothyroidism), one case of amiodarone-induced hypothyroidism discovered during this study, 5 cases of hypothyroidism without antibodies (two cases of compensated hypothyroidism with normal TRH stimulating test, two cases with severe liver cirrhosis and one case with chronic hepatitis). Twelve patients had antithyroid antibodies with normal TSH levels. The prevalence of ATPO and ATG antibodies in our study is similar to the prevalence usually observed in general population and does not suggest a pathogenic role of HCV in autoimmune thyroid disorders.

Sex differences in the control of sex-hormone-binding globulin in the elderly: role of insulin-like growth factor-I and insulin.

OBJECTIVE: Serum levels of sex-hormone-binding globulin (SHBG) have been reported in the literature to increase with age in both sexes. We have investigated the variations in levels of androgens, insulin and IGF-I with age and have evaluated their putative roles to obtain a better understanding of the increase in SHBG. DESIGN: Cross-sectional pilot study of blood samples in healthy elderly subjects aged 50 to 90 years. PATIENTS AND METHODS: Forty-four postmenopausal women and 40 men were classified into three age groups. Subjects who were obese, undernourished or smokers and postmenopausal women receiving hormone replacement therapy were excluded from the study. Body mass index and waist/hip ratio were evaluated in each subject. Fasting levels of blood glucose, insulin, triglycerides, cholesterol, SHBG, testosterone, dehydroepiandrosterone sulfate (DHEAS) and IGF-I were measured. Free testosterone and glucose/insulin ratio were calculated. RESULTS: The results are based on variance analysis of the mean of each parameter in the three age groups. Multiple regression analysis was performed to define the role of age, insulin and IGF-I in the increase in SHBG. The increase in SHBG with age in older men was significant but that in postmenopausal women was not. Decreasing DHEAS with age was confirmed. No significant variations in glucose and insulin were observed with age in our selected population. A positive correlation was observed between insulin and triglycerides in elderly men and women. IGF-I decreased significantly with age in both sexes. Insulin was the main factor explaining SHBG increase with age in women. In men, both age and IGF-I contributed to the SHBG increase. CONCLUSIONS: The factors regulating the increase in SHBG with age appear to be different in the two sexes. Insulin plays a major role in women, whereas a decrease in IGF-I is the predominant regulating factor in men. These results should be thought of as a working hypothesis rather than a reflection of physiology.

Relationship between abnormalities on high-resolution CT and pulmonary function in systemic sclerosis.

STUDY OBJECTIVES: To determine the predictive value of abnormalities on high-resolution CT (HRCT) on pulmonary disease in systemic sclerosis. PATIENTS: Fifty-two patients suffering from systemic sclerosis. DESIGN: Pulmonary disease was defined by pulmonary function test abnormalities, ie, total lung capacity (TLC) <80% of predicted value and/or diffusion of carbon monoxide (DLCO) <75% of predicted value, without any pulmonary event other than systemic sclerosis in the medical history. Patients were divided in two groups, group A with pulmonary disease (29 patients) and group B without pulmonary disease (23 patients). HRCT abnormalities were scored on whole lungs. A decision matrix was constructed to determine sensitivity, specificity, positive and negative predictive values, and false-positive and false-negative rates. A receiver operating characteristic curve was constructed to determine the best compromise between sensitivity and specificity. RESULTS: HRCT total scores were higher in group A (9.0+/-4.3) than in group B (5.0+/-2.8) (p < 0.001) and they correlated with TLC (r =-0.39, p < 0.005) and DLCO (r = -0.50, p < 0.0002). An HRCT score of 7 corresponded to the best compromise between sensitivity (0.60) and specificity (0.83), with a positive predictive value of 0.82. Taking into account a value of 10 for the HRCT score increased specificity to 1 but decreased sensitivity to 0.41. CONCLUSION: A minimum score of 7 would be required to consider HRCT abnormalities in systemic sclerosis as predictive of pulmonary disease. An HRCT score of 10 makes it possible to establish the diagnosis of lung involvement severe enough to impair pulmonary function.

Improved pharmacodynamics of L-asparaginase-loaded in human red blood cells.

To evaluate the modification of pharmacodynamic parameters induced by the administration of L-asparaginase loaded into red blood cells, 13 patients received a single dose of L-asparaginase internalised into the carrier. The enzyme was loaded using a reversible lysis-resealing process. The dose per patient ranged from 30 to 200 i.u. kg-1. Considerable heterogeneity occurred between patients. the level of L-asparaginase circulating after 24 h represented 47% of the total injected dose as compared to 74.8% for red blood cells (RBCs). However, the half-life of the enzyme remaining in the circulation was very similar to that of the RBC carrier, i.e. 29 days and 27 days, respectively, compared with 8-24 h for the free enzyme. Sustained elimination of plasma L-asparagine occurred, the duration of which was dependent on the injected dose. A single injection of 30.i.u.kg-1 was sufficient to eliminate plasma L-asparagine over 10 days. With 150-200 IU.kg-1 the elimination period was extended to 50 days. These data show that the use of RBCs as carriers of L-asparaginase greatly improves the pharmacodynamic parameters of the drug.

Imaging of pulmonary disease in rheumatoid arthritis using J001X scintigraphy: preliminary results.

The purpose of this study was to determine the ability of technetium-99m J001X scintigraphy to image active pulmonary involvement in patients suffering from rheumatoid arthritis (RA). J001X is a fully characterized acylated poly(1,3)galactoside, isolated from Klebsiella membranes, which is able to bind recruited macrophages after aerosol administration. J001X scintigraphy was compared with high-resolution computed tomography (HRCT), pulmonary function tests (PFTs) and bronchoalveolar lavage (BAL) in 15 patients suffering from RA. Patients were considered to have pulmonary involvement when they had an interstitial syndrome on HRCT and a decrease of 20% in TCO/VE (transfer coefficient) on PFTs and/or an abnormal BAL (lymphocytosis higher than 20% and/or percentage of neutrophils higher than 10%). Pulmonary involvement was present in eight patients, and absent in seven. Of the eight patients with pulmonary involvement, all had abnormal BAL, two had an interstitial syndrome on HRCT, two had decreased TCO/VE and three had positive J001X scintigraphy. Of the seven patients without pulmonary involvement, six had normal BAL (not available in one), two had an interstitial syndrome on HRCT, one had decreased TCO/VE and two had positive J001X scintigraphy. According to our gold standard of pulmonary involvement, the sensitivity of J001X scintigraphy for the detection of pulmonary involvement in RA was 37.5%, the specificity was 71.4% and the positive predictive value was 60%. The ability of J001X scintigraphy to detect active pulmonary involvement during RA appears unclear in this study but it may detect processes unnoticed by the other modalities. These patients will be followed 12 and 24 months later and the changes in J001X scintigraphy, HRCT and PFTs will be compared to demonstrate whether J001X scintigraphy is able to assess an active process in the pulmonary involvement during RA and to specify its predictive value.