Description of serum symmetric dimethylarginine concentration and of urinary SDS-AGE pattern in dogs with ACTH dependent hyperadrenocorticism.

Serum symmetric dimethylarginine (SDMA) and patterns of urinary protein separated by sodium dodecyl sulfate agarose gel electrophoresis (SDS-AGE) have not been investigated as biomarkers in dogs with ACTH-dependent hyperadrenocorticism (ADHAC). This exploratory prospective study aimed to evaluate SDMA, serum creatinine (sCR), and SDS-AGE in dogs with ADHAC with and without proteinuria (ADHAC-P and ADHAC-nP, respectively). Thirty-five pet dogs classified as ADHAC-P (n=16), ADHAC-nP (n=6) and healthy (n=13) were included. Renal biomarkers were evaluated in all dogs at diagnosis. Baseline concentration of SDMA was not significantly different between the three groups (P = 0.15) whereas sCr was significantly lower in dogs in ADHAC dogs compared to healthy dogs (88.0 µmol/L [70.4-132.6; 79.2-114.4]) whether they had proteinuria or not (P = 0.014 and 0.002, respectively). However, baseline concentrations of sCr and SDMA were not significantly different between dogs with ADHAC-P dogs (SDMA, 8 µg/dL [5-12; 7-9]; sCr, 57.2 µmol/L [35.2-212.2; 52.8-92.4]) and ADHAC-nP dogs (SDMA, 8.5 µg/dL [7-13; 8-10]; sCr, 70.4 µmol/L [61.6-79.2; 61.6-70.4]) (P = 0.35 and P = 0.41, respectively). Proteinuria in dogs with ADHAC-P was mainly of glomerular origin (SDS-AGE pattern: glomerular in 10/16 dogs; mixed glomerular/tubular in four dogs). In our study, SDMA was neither significantly different in dogs with ADHAC whether they were proteinuric or not, nor between ADHAC and healthy dogs. Urinary electrophoresis provides additional information to the UPC and further investigations are needed to determine whether it may help identify dogs with ADHAC-P requiring specific antiproteinuric treatment.

A versatile flexure-based six-axis force/torque sensor and its application to tribology.

Six-axis force/torque sensors are increasingly needed in mechanical engineering. Here, we introduce a flexure-based design for such sensors, which solves some of the drawbacks of the existing designs. In particular, it is backlash-free, it can be wirelessly monitored, it exactly enforces 90° angles between axes, and it enables visual inspection of the monitored system, thanks to its hollow structure. We first describe the generic design, implementation, and calibration procedure. We then demonstrate its capabilities through three illustration examples relevant to the field of tribology: low friction measurements under ultra-high vacuum, multi-directional friction measurements of elastomer contacts, and force/torque-based contact position monitoring.

Clinical description of Corynebacterium urealyticum urinary tract infections in 11 dogs and 10 cats.

OBJECTIVES: To examine the clinical signs, laboratory findings, possible predisposing factors, antimicrobial sensitivity and outcomes of dogs and cats diagnosed with urinary tract infection caused by Corynebacterium urealyticum. MATERIALS AND METHODS: Retrospective, observational study of dogs and cats that were diagnosed with urinary tract infection caused by C. urealyticum. RESULTS: This report concerns a total of 11 dogs and 10 cats. All cats had a history of urethral catheterisation, and six cats had undergone urological surgery before diagnosis of this specific infection. Dogs had history of neurogenic urinary incontinence (n=5), urethral catheterisation (n=4), urological surgery (n=4), lower urinary tract disease (n=2) or prostatic disease (n=1). In seven animals, previous urine culture was negative. Median urine pH was 8.6 (interquartile range 7.5 to 9), and 19 animals had pyuria and struvite crystalluria. Encrusted cystitis was diagnosed by abdominal ultrasound in nine animals. All but one isolate were resistant to at least three antimicrobial classes. Thirteen isolates were sensitive to tetracyclines. There was bacterial and clinical resolution of the infection in nine dogs and seven cats. Two animals died from sepsis and two cats were euthanased because of clinical deterioration. CLINICAL SIGNIFICANCE: Urinary tract infection caused by C. urealyticum should be suspected in animals with pre-existing urinary disorders, especially if urine is alkaline and there is struvite crystalluria, negative routine urine culture and encrusted cystitis.

Evolution of real contact area under shear and the value of static friction of soft materials.

The frictional properties of a rough contact interface are controlled by its area of real contact, the dynamical variations of which underlie our modern understanding of the ubiquitous rate-and-state friction law. In particular, the real contact area is proportional to the normal load, slowly increases at rest through aging, and drops at slip inception. Here, through direct measurements on various contacts involving elastomers or human fingertips, we show that the real contact area also decreases under shear, with reductions as large as 30[Formula: see text], starting well before macroscopic sliding. All data are captured by a single reduction law enabling excellent predictions of the static friction force. In elastomers, the area-reduction rate of individual contacts obeys a scaling law valid from micrometer-sized junctions in rough contacts to millimeter-sized smooth sphere/plane contacts. For the class of soft materials used here, our results should motivate first-order improvements of current contact mechanics models and prompt reinterpretation of the rate-and-state parameters.

Fibroblast Growth Factor 23 drives MMP13 expression in human osteoarthritic chondrocytes in a Klotho-independent manner.

OBJECTIVE: Fibroblast Growth Factor 23 (FGF23) may represent an attractive candidate that could participate to the osteoarthritic (OA)-induced phenotype switch of chondrocytes. To address this hypothesis, we investigated the expression of FGF23, its receptors (FGFRs) and co-receptor (Klotho) in human cartilage and studied the effects of rhFGF23 on OA chondrocytes. METHOD: Gene expression or protein levels were analysed by RT-PCR and immunohistochemistry. Collagenase 3 (MMP13) activity was measured by a fluorescent assay. MAPK signalling pathways were investigated by phosphoprotein array, immunoblotting and the use of selective inhibitors. RNA silencing was performed to confirm the respective contribution of FGFR1 and Klotho. RESULTS: We showed that the expression of FGF23, FGFR1 and Klotho was up-regulated at both mRNA and protein levels in OA chondrocytes when compared to healthy ones. These overexpressions were markedly elevated in the damaged regions of OA cartilage. When stimulated with rhFGF23, OA chondrocytes displayed an extended expression of FGF23 and of markers of hypertrophy such as MMP13, COL10A1, and VEGF. We demonstrated that FGF23 auto-stimulation was both FGFR1-and Klotho-dependent, whereas the expression of markers of hypertrophy was mainly dependent on FGFR1 alone. Finally, we showed that FGF23-induced MMP13 expression was strongly regulated by the MEK/ERK cascade and to a lesser extent, by the PI-3K/AKT pathway. CONCLUSION: These results demonstrate that FGF23 sustains differentiation of OA chondrocytes in a Klotho-independent manner.

Aggressiveness Changes in Populations of Didymella pinodes over Winter and Spring Pea Cropping Seasons.

UNLABELLED: Ascochyta blight, caused by the necrotrophic ascomycete Didymella pinodes, is responsible for severe losses in winter and spring pea crops. Despite different climatic conditions, epidemics on winter and spring crops are due to a single population of D. pinodes, suggesting gene flow either between the two crops or from reservoir sources during the cropping season. This should lead to similar pathogenicity characteristics in isolates sampled from the two crops. However, these hypotheses have never been formally tested. We therefore sampled a total of 520 D. pinodes strains throughout a growing season from winter and spring pea plots (WP and SP, respectively) and from winter and spring trap plants (TWP and TSP). Amplified fragment length polymorphism (AFLP) markers revealed high genetic diversity within subpopulations, whereas pathogenicity tests showed that mean aggressiveness increases over the course of an epidemic. These results support the idea that alloinoculum contributes to the carryover of epidemics between winter and spring crops and that the most aggressive isolates are selected as an epidemic progresses. IMPORTANCE: Ascochyta blight, caused by Didymella pinodes, is responsible for severe losses in pea crops. While previous studies have shown that ascochyta blight epidemics on winter and spring crops are due to a single population of D. pinodes, suggesting that isolates from the two crops present similar pathogenicity characteristics, that hypothesis have never been tested. Genetic analysis of subpopulations sampled throughout a growing season from winter and spring pea plots revealed high genetic diversity within subpopulations, whereas pathogenicity tests showed that mean aggressiveness increases over the course of an epidemic.

Effet paradoxal du type d'excision sur la prise et le délai de cicatrisation des greffes expansées pour le traitement des brûlures aiguës: a propos de 1129 cas.

Split-thickness meshed skin graft is frequently used in the treatment of acute burns. We studied the effect of the type of basement preparation on graft intake and healing time. We retrospectively analysed 1,129 meshed grafts used in the treatment of acute burns between 1995 and 2005. Intake was significantly better after avulsion (82%) than after tangential excision (75%). Intake was better if avulsion was performed before day 7 (83% vs. 73%). A trend for better intake after tangential excision was seen when performed between day 7 and 21. Healing time was significantly shorter after tangential excision. These results show the paradox that avulsion favours graft intake but delays healing time, contrary to tangential excision.

[Reduction mammaplasty in ambulatory: A prospective study of feasibility]. / Plasties mammaires de réduction en ambulatoire : étude prospective de faisabilité

OBJECTIVE: The French Ministry of Health and its regional agencies decided on December 27th, 2010 to develop the ambulatory surgery in the purpose to eliminate 48,000 beds of surgery in France. This evolution, which results from Anglo-Saxon countries, is inevitable in front of the financial deficit of our health insurance. Like the Canadian plastic surgeons, who were forced to it for 7 years, we wanted to study the feasibility of an ambulatory care of the reduction mammaplasties in a hospitalo-university department. METHODS: Between January and June, 2012, 25 patients, of less than 65 years old, were operated for a reduction mammaplasty scheduled in ambulatory. None presented particular anesthetic risk. All lived unless 1h of the hospital, went out accompanied, were revised the day after the intervention, then in a usual way. Our criterias of evaluation were the following ones: global satisfaction of the care in ambulatory, weight of glandular resection, postoperative complications, rate of readmission. RESULTS: The average age of the patients was 32 years (19-56 years). The average weight of resection was 400g by breast (140-1000g). Twenty patients went out on evening (80%). Among them, 19 (95%) expressed their satisfaction and would accept again this intervention in ambulatory. No major complication arose in this series. Five other patients saw their release repelled by the anaesthetists for the following motives: score of Aldrete lower than 9, pain not relieved by the analgesic (I or II), nausea and uncontrollable vomitings. CONCLUSION: This first clinical study realized in France, confirms that when certain conditions are filled, the reduction mammaplasty can be realized in ambulatory with complete safety. The rate of satisfaction shows a very strong support of the patients for the ambulatory care.

Quality of life in patients treated for advanced hypopharyngeal or laryngeal cancer.

OBJECTIVE: To study quality of life in patients treated for advanced hypopharyngeal or laryngeal cancer, with laryngeal conservation or laryngectomy. PATIENTS AND METHODS: A retrospective 2-center study included 100 patients in remission from squamous cell carcinoma, treated between 1998 and 2009. Seventy patients (24 hypopharynx, 46 larynx) were treated by total (pharyngo-) laryngectomy followed by external radiation therapy, and 30 (13 hypopharynx, 17 larynx) underwent an organ-conservation protocol with concurrent radiochemotherapy or with induction chemotherapy using platin-5FU or taxan-platin-5FU followed by radiation therapy. All patients responded to the quality of life questionnaires (EORTC QLQ-C30 and QLQ-H&N35). RESULTS: Advanced tumor stages IVa and IVb were significantly more frequent in the surgery groups (hypopharynx: 71.6% vs. 45.9%, p=0.01; larynx: 72.4% vs. 37.5%, p<0.01). In pharyngeal cancer, the only significant difference between surgical treatment and laryngeal conservation was for "sensory disorder" (taste and odor), with better results in case of laryngeal conservation (p<0.0001). For the other items, there was a trend for quality of life to appear better in patients with laryngeal conservation (p=NS). In laryngeal cancer, the only significant difference was for "dry mouth", which was significantly less invalidating with surgical treatment (p<0.001). The impairment of the other quality of life items did not differ between surgical and conservative treatment. CONCLUSIONS: Quality of life is impaired in all patients treated for pharyngeal or laryngeal cancer. The type of treatment, surgical or conservative, affects differently various aspects of quality of life.

[Multiple brain abscesses complicating Enterobacter cloacae sepsis in a premature infant]. / Abcès cérébraux multiples à Enterobacter cloacae chez un prématuré. Intérêt de la ciprofloxacine.

A neonatal infection with Enterobacter cloacae was diagnosed at day 21 in a premature infant. Five cerebral abscesses were discovered 6 days while a treatment with cefotaxim and amikacin was administered. We switched for axepim during 4 weeks and ciprofloxacin until complete regression of cerebral abscesses. At 13 months of age, the infant neurodevelopmental outcome was normal. Ciprofloxacin indications and tolerance during neonatal period are discussed.

New combinations of mutations in VanD-Type vancomycin-resistant Enterococcus faecium, Enterococcus faecalis, and Enterococcus avium strains.

We studied the clinical isolates Enterococcus faecium NEF1, resistant to high levels of vancomycin (MIC, 512 microg/ml) and teicoplanin (MIC, 64 microg/ml); Enterococcus faecium BM4653 and BM4656 and Enterococcus avium BM4655, resistant to moderate levels of vancomycin (MIC, 32 microg/ml) and to low levels of teicoplanin (MIC, 4 microg/ml); and Enterococcus faecalis BM4654, moderately resistant to vancomycin (MIC, 16 microg/ml) but susceptible to teicoplanin (MIC, 0.5 microg/ml). The strains were distinct, were constitutively resistant via the synthesis of peptidoglycan precursors ending in D-alanyl-D-lactate, and harbored a chromosomal vanD gene cluster that was not transferable. New mutations were found in conserved domains of VanS(D): at T(170)I near the phosphorylation site in NEF1, at V(67)A at the membrane surface in BM4653, at G(340)S in the G2 ATP-binding domain in BM4655, in the F domain in BM4656 (a 6-bp insertion), and in the G1 and G2 domains of BM4654 (three mutations). The mutations resulted in constitutivity, presumably through the loss of the phosphatase activity of the sensor. The chromosomal Ddl D-Ala:D-Ala ligase had an IS19 copy in NEF1, a mutation in the serine (S(185)F) or near the arginine (T(289)P) involved in D-Ala1 binding in BM4653 or BM4655, respectively, and a mutation next to the lysine (P(180)S) involved in D-Ala2 binding in BM4654, leading to the production of an impaired enzyme. In BM4653 vanY(D), a new insertion sequence, ISEfa9, belonging to the IS3 family, resulted in the absence of D,D-carboxypeptidase activity. Strain BM4656 had a functional D-Ala:D-Ala ligase, associated with high levels of both VanX(D) and VanY(D) activities, and is the first example of a VanD-type strain with a functional Ddl enzyme. Study of these five clinical isolates, displaying various assortments of mutations, confirms that all VanD-type strains isolated so far have undergone mutations in the vanS(D) or vanR(D) gene, leading to constitutive resistance, but that the Ddl host ligase is not always impaired. Based on sequence differences, the vanD gene clusters could be assigned to two subtypes: vanD-1 and vanD-4.

[Major orbital complications of acute maxillary sinusitis of dental aetiology]. / Complications orbitaires majeures des sinusites maxillaires aiguës d'origine dentaire.

OBJECTIVES: To demonstrate the importance of searching for a dental aetiology when confronted with an orbital cellulitis secondary to an acute unilateral maxillary sinusitis and to diagnose and treat as soon as possible in order to avoid visual sequelae. CASE REPORT: Two cases are presented. The first case of a 35 year-old man who was diagnosed and treated late, for an orbital abscess secondary to a sinusitis of dental origin. The patient presented with visual signs such as diplopia and impaired occulomotoricity. The clinical diagnosis was concluded by an emergency sinus CT scan. Treatment consisted of an urgent surgical drainage associated to broad spectrum antibiotics with a high spectrum against Gram +cocci and anaerobes. Dispite this treatment regimen and two subsequent surgeries, the evolution was pejorative ending in a unilateral blindness. The second case is of a 45 year-old immunodeficient woman, presenting with the same pathology but without visual signs and whose evolution was satisfactory after adapted surgical and medical treatments. DISSCUSSION: The presence of visual and ocular signs warn on the gravity of the infection and indicate the need for urgent surgery. Sinus CT scan is essential to highlight the association between the orbit and the causal dental infection. For that, it must include the alveolar processes of the maxilla to show the dental lesion which is usually missed clinically. Functional endoscopic sinus surgery achieves two goals here; one diagnostic by the direct exploration of the nasal sinus cavities and the other therapeutic by the possible drainage all the paranasal sinuses.

Unusual etiology of visual loss in an HIV-infected patient due to endogenous endophthalmitis.

Disseminated candidiasis, especially ocular infections such as endophthalmitis, is uncommon in HIV-infected patients. We report a case of candidal endophthalmitis in an HIV-positive non-drug-user patient, following candidemia from a cutaneous abscess at the site of a peripheral catheter. Ocular disease was revealed by a visual decrease in the left eye. DNA analysis using RAPD showed identical patterns of Candida albicans isolated from the skin and eye. Combination therapy with high-dose fluconazole and intravenous amphotericin B was performed. Two intravitreal amphotericin B injections and a vitrectomy were administered because of an amblyopic right eye and severe vitritis. The outcome was favorable without relapse at 18 months.

Acute pancreatitis caused by severe Legionella pneumophila infection.

We report three cases of severe community-acquired Legionella pneumophila pneumonia with acute pancreatitis. Pancreas involvement is unusual. The clinical presentations consisted of painless pancreatitis with only elevation of serum pancreatic enzymes (case 1), tender abdomen with edematous pancreas on computed tomography scan (case 2) and necrosis (case 3). We discuss the possible mechanisms of L. pneumophila associated acute pancreatitis for which the pathophysiology is still undetermined: infection, toxin release or cytokine secretion.

Maternal-fetal staphylococcal infections: a series report.

The objective of this paper is to study the characteristics of maternal-fetal staphyloccocal infection. A retrospective study among 1,582 infants admitted consecutively to our neonatal intensive care unit was carried out from January 1995 through September 1998. The antenatal history, and the clinical and bacteriological findings and outcome of the infants fulfilling maternal-fetal staphyloccocal infection were analysed. Among 122 (7.7%) maternal-fetal infection, 11 cases (8.9%) of congenital staphyloccal infections were diagnosed in 9 premature and 2 full-term babies. Antenatal invasive procedures were noted in 6 occasions (56%). All the 11 infants developed respiratory and hemodynamic failure. Staphylococcus aureus was the most common organism encountered in maternal bacteriologic data (9/11, 82%) as well as on peripheral sites (9/11, 82%) and in blood cultures (7/11, 64%) performed in the infants. There was one case of methicillin-resistant Staphylococcus aureus. The outcome was favorable for 9 infants. Two very preterm neonates died within the first 72 hours of life. Mother-to-infant transmission of Staphylococcus should be suspected whenever invasive procedures are performed during pregnancy and in the presence of severe neonatal distress associated with an inflammatory response. Prompt and adapted antibiotic therapy allows a favourable outcome.

Microbiology in sudden infant death syndrome (SIDS) and other childhood deaths.

The usefulness of post-mortem microbiology in the assessment of sudden unexpected deaths in infants and children has been debated by many pathologists. In our centre, microbiological investigations have been part of the post-mortem protocol for investigation of sudden deaths in infants and children for the past 12 years. The objective of this study was to review the microbiological findings for infants and children examined by our unit during the past 4 years in relation to gross and histological findings of the autopsy and the medical and social histories of the children. We reviewed 57 consecutive sudden deaths in infants and children examined by our Referral Centre between November 1994 and October 1998. These 57 sudden deaths were aged from 1 day to 4 years and 9 months including 40 cases of sudden infant death syndrome (SIDS) and 17 non-SIDS deaths. Results of the microbiological investigations of tissues and body fluids were assessed during the case review with reference to histological shock signs, severe gastric aspiration, and signs of acute thymic involution. Bacteria alone or in association with viruses were identified in 45/57 (79%) cases including 34/40 (85%) SIDS. The most frequent bacterial isolate was Escherichia coli (27), and the virus identified most frequently was enterovirus (8). C-reactive protein was increased in 10 out of the 42 cases tested including 8/32 (25%) SIDS. Significant gastric content aspiration was found in 17/57 (29.8%) including 13/40 (32.5%) SIDS. Histological signs of shock were present in 33/55 (60%) cases including 22/39 SIDS (56.4%). The microbiological findings were positive for 27/33 (81.8%). We conclude that post-mortem microbiology is essential in sudden death investigation. The conclusion that a death is unexplained if no microbiology was done is not valid, even if in some cases it may be difficult to know precisely in what way the pathogen contributed to the death.

Integron- and carbenicillinase-mediated reduced susceptibility to amoxicillin-clavulanic acid in isolates of multidrug-resistant Salmonella enterica serotype typhimurium DT104 from French patients.

Fifty-seven Salmonella enterica serotype Typhimurium (S. typhimurium) isolates were collected from human patients in two French hospitals, Hôpital Antoine Béclère (Clamart, France) and Hôpital Bicêtre (Le Kremlin-Bicêtre, France), between 1996 and 1997. Thirty of them (52 percent) were resistant to amino-, carbeni-, and ureidopenicillins, had reduced susceptibility to amoxicillin-clavulanic acid, were susceptible to cephalothin, and were resistant to sulfonamides, streptomycin, chloramphenicol, and tetracyclines. All these strains possessed a blaPSE-1-like gene and were of phage type DT104. Ten of them were studied in more detail, which revealed that blaPSE-1 is located on the variable region of a class 1 integron. This integron was found to be chromosomally located, as was another class 1 integron containing aadA2, a streptomycin-spectinomycin resistance gene. The reduced susceptibility to amoxicillin-clavulanic acid (and to ticarcillin-clavulanic acid) may result from the high level of hydrolysis of the beta-lactam rather than to the clavulanic acid resistance properties of PSE-1 in these clonally related S. typhimurium isolates.

Cloning, sequence analyses, expression, and distribution of ampC-ampR from Morganella morganii clinical isolates.

Shotgun cloning experiments with restriction enzyme-digested genomic DNA from Morganella morganii 1, which expresses high levels of cephalosporinase, into the pBKCMV cloning vector gave a recombinant plasmid, pPON-1, which encoded four entire genes: ampC, ampR, an hybF family gene, and orf-1 of unknown function. The deduced AmpC beta-lactamase of pI 7.6 shared structural and functional homologies with AmpC from Citrobacter freundii, Escherichia coli, Yersinia enterocolitica, Enterobacter cloacae, and Serratia marcescens. The overlapping promoter organization of ampC and ampR, although much shorter in M. morganii than in the other enterobacterial species, suggested similar AmpR regulatory properties. The MICs of beta-lactams for E. coli MC4100 (ampC mutant) harboring recombinant plasmid pACYC184 containing either ampC and ampR (pAC-1) or ampC (pAC-2) and induction experiments showed that the ampC gene of M. morganii 1 was repressed in the presence of ampR and was activated when a beta-lactam inducer was added. Moreover, transformation of M. morganii 1 or of E. coli JRG582 (delta ampDE) harboring ampC and ampR with a recombinant plasmid containing ampD from E. cloacae resulted in a decrease in the beta-lactam MICs and an inducible phenotype for M. morganii 1, thus underlining the role of an AmpD-like protein in the regulation of the M. morganii cephalosporinase. Fifteen other M. morganii clinical isolates with phenotypes of either low-level inducible cephalosporinase expression or high-level constitutive cephalosporinase expression harbored the same ampC-ampR organization, with the hybF and orf-1 genes surrounding them; the organization of these genes thus differed from those of ampC-ampR genes in C. freundii and E. cloacae, which are located downstream from the fumarate operon. Finally, an identical AmpC beta-lactamase (DHA-1) was recently identified as being plasmid encoded in Salmonella enteritidis, and this is confirmatory evidence of a chromosomal origin of the plasmid-mediated cephalosporinases.

Molecular and biochemical characterization of VEB-1, a novel class A extended-spectrum beta-lactamase encoded by an Escherichia coli integron gene.

A clinical isolate, Escherichia coli MG-1, isolated from a 4-month-old Vietnamese orphan child, produced a beta-lactamase conferring resistance to extended-spectrum cephalosporins and aztreonam. In a disk diffusion test, a typical synergistic effect between ceftazidime or aztreonam and clavulanic acid was observed along with an unusual synergy between cefoxitin and cefuroxime. The gene for VEB-1 (Vietnamese extended-spectrum beta-lactamase) was cloned and expressed in E. coli JM109. The recombinant plasmid pRLT1 produced a beta-lactamase with a pI of 5.35 and conferred high-level resistance to extended-spectrum (or oxyimino) cephalosporins and to aztreonam. Vmax values for extended-spectrum cephalosporins were uncommonly high, while the affinity of the enzyme for ceftazidime and aztreonam was relatively low. blaVEB-1 showed significant homology at the DNA level with only blaPER-1 and blaPER-2. Analysis of the deduced protein sequence showed that VEB-1 is a class A penicillinase having very low levels of homology with any other known beta-lactamases. The highest percentage of amino acid identity was 38% with PER-1 or PER-2, two uncommon class A extended-spectrum enzymes. Exploration of the genetic environment of blaVEB-1 revealed the presence of gene cassette features, i.e., (i) a 59-base element associated with blaVEB-1; (ii) a second 59-base element just upstream of blaVEB-1, likely belonging to the aacA1-orfG gene cassette; (iii) two core sites (GTTRRRY) on both sides of blaVEB-1; and (iv) a second antibiotic resistance gene 3' of blaVEB-1, aadB. blaVEB-1 may therefore be the first class A extended-spectrum beta-lactamase that is part of a gene cassette, which itself is likely to be located on a class 1 integron, as sulfamide resistance may indicate. Furthermore, blaVEB-1 is encoded on a large (> 100-kb) transferable plasmid found in a Klebsiella pneumoniae MG-2 isolated at the same time from the same patient, indicating a horizontal gene transfer.