[Necrotic leg ulcers after topical application of chlormethine]. / Ulcères de jambe nécrotiques après application locale de chlorméthine.

BACKGROUND: Topical chlormethine has been widely used in the early stages of mycosis fungoides for many years. Cutaneous reactions (skin irritation and itch) are the most frequent adverse effects. Herein we report a rare side effect: severe necrotic leg ulcers. PATIENTS AND METHODS: An 82-year-old woman with a history of high blood pressure developed hyperalgesic necrotic ulcers on the lower limbs following local trauma one month after initiation of topical chlormethine (Valchlor®) to treat mycosis fungoides. Aetiological examination showed moderate peripheral arterial disease which, while constituting an aggravating factor, did not account fully for these skin ulcers. Moreover, drug-induced ulcer was suspected on account of the chronology. Dermal corticoids and topical treatment were prescribed in place of chlormethine and led to a favourable outcome. CONCLUSION: Incrimination of chlormethine was based on the chronological and semiological criteria. This is the first published case of leg ulceration induced by Valchlor®.

Supervised short-stretch compression therapy in mixed leg ulcers.

OBJECTIVES: This study was conducted to determine hemodynamic and clinical tolerance under short-stretch compression therapy in elderly patients suffering from mixed-etiology leg ulcers. DESIGN: Transversal observational study conducted in 25 hospitalized patients with a moderate peripheral arterial occlusive disease defined as an ankle-brachial pressure index>0.5, an ankle pressure of>70mmHg and a toe cuff pressure (TP)>50mmHg. MATERIAL AND METHODS: Short-stretch bandages were applied daily with pressures from 20 to 30mmHg. Ankle-brachial pressure, great toe laser Doppler flowmetry (LDF) and transcutaneous oxygen pressure (TcPO2) on dorsum of the foot were measured at baseline and after its removal at 24hours. Great toe LDF was also measured at 10minutes after bandage application. Compression pressure (CP) was measured with a sub-bandage device at baseline, at 10minutes and before bandage removal at 24hours. Clinical tolerance was evaluated taking into account the patient's pain and skin tolerance. RESULTS: Mean age of patients was 80±15 years. Median duration of ulcers was 18 months. Hypertension was highly prevalent. One third of patients had diabetes. Toe pressure index and TcPO2 values did not significantly change under compression therapy (P=0.51 and P=0.09, respectively) whereas CP decreased significantly during 24hours. The loss of CP was significant 10minutes after bandage application (P<0.001). Nearly all ulcers were painful prior to placement of compression therapy and required level 1 analgesics. One patient required level 2 analgesic for pain relief. No increase in pain and no ischemic skin damage occurred under compression therapy. CONCLUSIONS: In elderly patients with mixed leg ulcers and with an absolute TP>50mmHg, short-stretch compression of up to 30mmHg does not adversely affect arterial flow and appears clinically well tolerated. Such bandages with appropriate levels of compression may aid ulcer healing by treating the venous part of the disease.

[When to ask for a skin biopsy in a patient with leg ulcer? Retrospective study of 143 consecutive biopsies]. / Quand poser l'indication d'une biopsie cutanée chez un patient porteur d'ulcère de jambe ? Étude rétrospective sur 143 biopsies consécutives.

OBJECTIVE: A vascular cause is found in around 85% of leg ulcer patients, but non-vascular causes are also observed. Their diagnosis is based on a set of clinical arguments and skin biopsy with histological analysis. The aim of this study was to analyze the results of these biopsies and to find common criteria for ulcers whose skin biopsies had led to the diagnosis of a non-vascular ulcer. MATERIAL AND METHOD: A retrospective study was carried out on the analysis of 143 skin biopsies of leg ulcers. The reasons for the biopsy were mainly atypical clinical signs and/or the lack of improvement in care after 6 months, as advocated by the French health authorities. RESULTS: The skin biopsies led to a diagnosis of non-vascular ulcer in 4.9% of cases (7/143), including skin cancer (n=5, 3.5%), cutaneous leishmaniasis (n=1, 0.7%) and Pyoderma gangrenosum (n=1, 0.7%). The univariate statistical analysis revealed that an elevated rim and abnormal excessive granulation tissue were significantly more frequently found in these ulcers. All patients with a positive skin biopsy had associated vascular involvement. CONCLUSION: This study found a 5% rate of non-vascular causes of ulcers, mainly skin cancer. Elevated rims and abnormal excessive granulation tissue were the unusual features most commonly found in these ulcers. All patients whose skin biopsy revealed a non-vascular cause had associated vascular involvement. This information confirms the need to perform a skin biopsy, even in the presence of a vascular disease.

[Deep venous thrombosis of the upper limb in a violin player: The "bow syndrome"]. / Thrombose veineuse profonde du membre supérieur chez une violoniste : « le syndrome de l'archet ¼.

BACKGROUND: Exercise-induced thrombosis is a rare cause of deep venous thrombosis (DVT) of the upper limb and usually affects young subjects without comorbid conditions. The diagnosis may be challenging. CASE REPORT: A 23-year-old female right-handed French teacher and amateur violin player presented with edema of the root of the right arm associated with erythrocyanosis of the extremity and collateral circulation of the shoulder. History taking revealed oral contraception and recent change in violin playing habits. D-dimers were negative. A second duplex-Doppler was required before visualization of a DVT in the right subclavian vein. The patient was given low-molecular-weight heparin alone, followed by rivaroxaban. The outcome was very favorable at 48h. The patient was seen at 4 months and had not had a recurrent episode. DISCUSSION: The diagnosis of DVT of the upper limb is basically clinical. There is a clinical probability score for the introduction of anticoagulation even if the duplex-Doppler fails to visualize DVT, a situation that can occur due to the clavicular superposition in this region. Exercise-induced DVT should be suspected in patients with minimally intense but repeated exercise (hyper-abduction), e.g. as here playing the violin. Anticoagulation is the treatment of choice. The role for surgery and pharmacomechanical strategies remains to be defined. CONCLUSION: Exercise-induced thrombosis (Paget-Schroetter syndrome) should be suspected in young patients free of any comorbidity who develop a thrombosis of the upper limb. Studies comparing different therapeutic options would be useful to achieve more homogeneous management practices despite the heterogeneous clinical presentations.

[Peripheral artery occlusive disease of the lower limbs: Rapid aggravation in a patient taking nilotinib for chronic myeloid leukemia]. / Artériopathie des membres inférieurs d'aggravation rapide chez un patient traité par nilotinib pour leucémie myéloïde chronique.

The development of tyrosine kinase inhibitors (TKI) has revolutionized management of patients with chronic myeloid leukemia (CML), transforming this fatal disease into a chronic disease with nearly normal life expectancy. Nilotinib is a second generation TKI targeting the oncoprotein BCR-ABL used in patients in the chronic phase of CML. Several research teams have suggested over recent years that nilotinib might be the causal agent in the development or aggravation of vascular disease, particularly in patients with cardiovascular risk factors or an established cardiovascular disease. We report here the case of a patient who developed severe peripheral arterial disease of the lower limbs that worsened despite optimal medical and surgical care, presenting recurrent re-stenoses after different revascularization techniques (bypass, angioplasty…) associated with aggravation of severe trophic disorders to the point of potentially requiring amputation. Discontinuation of nilotinib enabled a stabilization of the arterial lesions and complete healing of the trophic lesions. This case illustrates the importance of recognizing co-morbid conditions in patients with severe vascular disease and to examine the possibility of drug interactions leading to rapid aggravation of arterial disease with no other cause. Studying the pathophysiological impact of TKIs on the vascular system may open new avenues of research for the investigation of factors triggering arteriosclerosis.

[Portal vein thrombosis associated with an acute cytomegalovirus infection]. / Thrombose portale associée à une infection aiguë à cytomégalovirus.

UNLABELLED: Portal vein thrombosis is an unusual condition and its association with an acute cytomegalovirus (CMV) infection is known but rarely reported. We present here the case of a 24-year-old woman suffering from a symptomatic portal vein thrombosis, confirmed by CT angiography, and acute CMV-related hepatitis. Besides a second generation oral contraceptive with estrogen and progesterone, not associated with smoking, the acute CMV infection was the only cause found to have provoked the venous thrombosis; a myeloproliferative disorder or biological thrombophilia were ruled out. The patient rapidly recovered with vitamin K antagonists (VKA) anticoagulant treatment. Eighteen cases of splanchnic vein thrombosis complicating acute CMV infection were found in the literature. All patients had acute hepatitis. The outcome was usually favorable with warfarin therapy for a period lasting 3 to 7 months. Antiviral treatment (anti-CMV) was used in three cases of severe infection. The antiviral therapy was given only in immunosuppressed patients. For immunocompetent patients, CMV infection is usually asymptomatic and clinical signs are often non-specific and mild, not requiring treatment. CONCLUSION: This case report and the review of the literature recall the need to search for acute CMV infection in patients with portal thrombosis so a possible transient trigger for venous thromboembolism can be identified, avoiding extended anticoagulation.

Evaluation under real-life conditions of a stand-alone fall detector for the elderly subjects.

BACKGROUND AND OBJECTIVES: Elderly patients unable to get up after a fall or to activate an alarm mechanism are particularly at risk of complications and need to be monitored with extreme care. The different risk factors have fostered the development of stand-alone devices facilitating early detection of falls. We aimed at assessing performance of the Vigi'Fall(®) system, a cutting edge fall detector associating a "passive release" mechanism attached to the patient and including external sensors; in the event of a fall, the system automatically triggers an alarm, and it also incorporates embedded confirmation software. We have put it to the test under real-life conditions so as to evaluate not only its efficacy, but also and more particularly its acceptability and tolerability in elderly subjects. METHOD: The study ran from March 2007 through December 2008 in a geriatric ward with 10 subjects over 75 years of age, all of whom presented with a risk of falling. RESULTS: For eight patients wearing an accelerometric sensor, eight "falling" events and 30 "alarm release" events were recorded. Sensitivity and specificity of the device came to 62.5 and 99.5% respectively. For the two patients wearing the complete device, no events were detected. Not a single adverse occurrence was noted. Local tolerance was excellent in all but one of the subjects. CONCLUSION: Our results clearly show that the device may be worn by patients without discomfort over prolonged periods of time, and also demonstrate that the verification component will help to increase sensitivity in real-life conditions to a level comparable to the level attained in our laboratory studies.

Diversity in VIM-2-encoding class 1 integrons and occasional blaSHV2a carriage in isolates of a persistent, multidrug-resistant Pseudomonas aeruginosa clone from Tunis.

From 2002 to 2006, 35 of 73 multidrug-resistant Pseudomonas aeruginosa isolates from different wards at Charles Nicolle hospital of Tunis were positive for class B carbapenemase (using the imipenem-EDTA test), owing to a bla(VIM-2) gene cassette in a class 1 integron. Twenty-three isolates additionally produced the extended-spectrum beta-lactamase SHV2a. DNA sequences immediately surrounding bla(SHV2a) shared extensive identity with a Klebsiella pneumoniae plasmid sequence. Despite belonging to the same chromosomal type, as shown by pulsed-field gel electrophoresis (PFGE), the VIM-2 producing P. aeruginosa isolates prevalent at Charles Nicolle hospital displayed a diversity of VIM-2-carrying integrons.

Functional interaction of HTLV-1 tax protein with the POZ domain of the transcriptional repressor BCL6.

The Tax protein encoded by human T-cell leukaemia virus type 1 (HTLV-1) has a pivotal role in T-cell transformation by deregulating cellular signalling pathways. Using the yeast two-hybrid system to screen a human leukocyte cDNA library, we identified BCL6 (B-cell lymphoma 6) as a cellular protein, which interacts with Tax 1. The BCL6 gene encodes a sequence-specific transcriptional repressor that contains a conserved N-terminal poxvirus and zinc finger (POZ) repressor domain and a C-terminal Kruppel-like zinc finger DNA binding domain. Using both in vivo and in vitro methods, we demonstrate that the POZ domain of BCL6 is sufficient for its interaction with Tax 1. Using functional assays, we demonstrate that Tax 1 enhanced the repressive activity of BCL6 and increased the levels of apoptosis induced by BCL6 in osteosarcoma cells indicating that both proteins cooperate in vivo to cause a physiological affect. Furthermore, BCL6 recruited Tax 1 into punctate nuclear structures, which suggests that Tax 1 colocalizes with BCL6 in repressor complexes in vivo. BCL6 expression significantly downregulated both basal and Tax-induced nuclear factor-kappaB and long terminal repeat activation. This suggests that the expression of BCL6 in HTLV infected cells may contribute to the silencing of viral gene expression and to the long clinical latency associated with HTLV infection.

Genetic context of plasmid-carried blaCMY-2-like genes in Enterobacteriaceae.

Analysis of 15 European clinical Enterobacteriaceae isolates showed that differences in the genetic context of blaCMY-2-like genes reflected the replicon type, usually IncA/C or IncI1. These blaCMY-2 loci may originate from the same ISEcp1-mediated mobilization from the Citrobacter freundii chromosome as structures described in earlier studies.

Prevalence and characterization of extended-spectrum beta-lactamases in Klebsiella pneumoniae in Algiers hospitals (Algeria).

AIM OF THE STUDY: To determine the prevalence and the diversity of extended-spectrum beta-lactamases (ESBLs) in 196 Klebsiella pneumoniae clinical isolates collected from three hospitals in Algiers. MATERIALS AND METHODS: Antibiograms were done on Mueller-Hinton agar plates with the disc-diffusion method and MICs were determined by agar-dilution method. Mating experiments were performed in agar medium. Plasmid DNA was extracted by the alcalin-lysis method. Total DNA was extracted with a Qiagen mini kit and screened for bla(TEM) and bla(CTX-M) genes by PCR. Linkage of bla(CTX-M) genes with insertion sequence ISEcp1B and class 1 integrons was investigated by PCR. PCR products were sequenced by the Sanger method. The epidemiological relationships between ESBL-producing K. pneumoniae isolates were analyzed by ERIC-PCR. RESULTS: Thirty-nine (19.9%) isolates were found to produce ESBLs belonging to CTX-M-1 group and TEM penicillinases (CTX-M-3, CTX-M-15 and TEM-1). ERIC-PCR analysis showed that the isolates are genetically unrelated. The bla(TEM) and bla(CTX-M) genes as well as aminoglycosides and sulfonamides resistance determinants were found located in self-transferable plasmids of approximately 85 kb. The class 1 integrons and the insertion sequence ISEcp1B were present in the isolates and in their transconjugants. ISEcp1B was found genetically linked to the bla(CTX-M) genes and located 127bp upstream, with the presence of the V and W sequences. CONCLUSION: The study revealed a high rate of ESBL-producing K. pneumoniae in Algerian hospitals, resulting from horizontal dissemination of mobile bla(CTX-M) genes.

Genetic environment of acquired bla(ACC-1) beta-lactamase gene in Enterobacteriaceae isolates.

We studied the genetic organization of bla(ACC-1) in 14 isolates of Enterobacteriaceae from France, Tunisia, and Germany. In a common ancestor, ISEcp1 was likely involved in the mobilization of this gene from the Hafnia alvei chromosome to a plasmid. Other genetic events involving insertion sequences (particularly IS26), transposons (particularly Tn1696), or sulI-type integrons have occurred, leading to complex genetic environments.

Clonal dissemination of a CTX-M-15 beta-lactamase-producing Escherichia coli strain in the Paris area, Tunis, and Bangui.

One hundred twenty CTX-M-15-producing Escherichia coli strains isolated in 10 different hospitals from Paris (France), in the Hospital Charles Nicolle in Tunis (Tunisia), and in the Pasteur Institute in Bangui, Central African Republic (CAR), between 2000 and 2004 were studied. Eighty isolates, recovered from the three countries, were clonally related by repetitive extragenic palindromic PCR and pulsed-field gel electrophoresis. Various resistance profiles were identified among these clonal strains. After conjugation or electroporation of plasmids from E. coli strains representative of each profile and each geographic region, we observed seven resistance profiles in the recipient strains. Incompatibility typing showed that all the plasmids transferred from the clonal strains studied, except one, belonged to the incompatibility group FII. They all shared a multidrug resistance region (MDR) resembling the MDR region located in pC15-1a, a plasmid associated with an outbreak of a CTX-M-15-producing E. coli strain in Canada. They also shared the common backbone of an apparent mosaic plasmid, including several features present in pC15-1a and in pRSB107, a plasmid isolated from a sewage treatment plant. This study suggests that although the plasmid-borne blaCTX-M-15 gene could be transferred horizontally, its dissemination between France, Tunisia, and CAR was due primarily to its residence in an E. coli clone with a strong propensity for dissemination.

DNA sequence analysis of the genetic environment of various blaCTX-M genes.

OBJECTIVES: Over a 3 year period (2000-2003) 21 Escherichia coli, 5 Klebsiella pneumoniae, 1 Serratia marcescens and 1 Proteus mirabilis producing CTX-M-type beta-lactamase were collected from five different hospitals in Paris, France. This study was conducted to analyse the genetic environment of these 28 bla(CTX-M) genes. METHODS: Antimicrobial susceptibility testing was performed by the disc diffusion method and MICs of various beta-lactams were determined by an agar dilution method. PCR was used to detect and sequence alleles encoding CTX-M, TEM, SHV and CMY enzymes. The genetic environment was analysed by amplification and direct sequencing using various set of PCR primers or cloning in pBK-CMV. RESULTS: Sequence analysis revealed that these isolates contained seven different bla(CTX-M) genes: bla(CTX-M-1) (4 strains), bla(CTX-M-2) (2 strains), bla(CTX-M-3) (4 strains), bla(CTX-M-9) (1 strain), bla(CTX-M-14) (5 strains), bla(CTX-M-15) (11 strains), bla(CTX-M-24) (1 strain). TEM-1 was associated with CTX-M-type enzymes in 15 isolates. Two strains produced both CTX-M-15 and SHV-2 or CTX-M-14 and CMY-2. In 25 strains the insertion sequence ISEcp1 was located upstream of the 5' end of the bla(CTX-M) gene. Among these strains, in five isolates, ISEcp1 was disrupted by insertion sequences such as IS26 (in three of them) or IS1 or IS10. Insertion sequence IS903 was found downstream of bla(CTX-M-14) or bla(CTX-M-24). Examination of the other three bla(CTX-M) genes (two bla(CTX-M-2) and one bla(CTX-M-9)) by cloning, sequencing and PCR analysis revealed the presence of complex Class 1 integrons, In35, an integron similar to In60 and a novel integron. CONCLUSIONS: This work further confirmed the predominant role of ISEcp1 in the mobilization of bla(CTX-M) genes of the CTX-M-1 cluster and the presence of In35, of an integron similar to In60 and a novel complex Class 1 integron.

First description of DHA-1 ampCbeta-lactamase in Proteus mirabilis.

This report describes the first occurrence of the DHA-1 ampCbeta-lactamase gene in Proteus mirabilis. The organism was isolated from the vaginal flora of a pregnant woman in a French hospital. The DHA-1 beta-lactamase gene was identified on the basis of phenotypic characteristics, PCR amplification and sequencing. Antagonism between cefoxitin and the other cephalosporins suggested inducible production of the DHA-1 enzyme.

[Spontaneous thrombosis of lesion-free carotid arteries: a retrospective analysis of eight patients]. / Thrombus endoluminal de l'artère carotide sans lésion sous-jacente. Etude rétrospective de 8 patients.

Strokes are rarely secondary to spontaneous carotid artery thrombosis. The objectives of this retrospective analysis were to define characteristic features and the clinical course. The study population included eight patients (6 females/2 males) seen at six university neurological centers. Age of onset was 46.5 years (range 38-52). Half of the patients had no vascular risk factor. Symptoms were TIA (n=1), strokes (n=7). Echotomography revealed intraluminal thrombus, with occlusion in 2 cases. Thrombi were found in common carotid artery (n=3), carotid bifurcation (n=2) and internal carotid artery (n=3). The thrombus was mobile in 4 cases. Seven patients were treated by anticoagulation therapy, one by surgery because of recurrent TIA. Further echotomographic exams revealed total resolution (3 cases) or decrease of the thrombus (3 cases). Occlusion was definitive in one patient. A cause was identified in six patients: acute leukemia (n=1), thrombocytopenic purpura (n=1), iron deficiency anemia (n=4).

[Home-based pulmonary rehabilitation: the evidence, practical issues and medico-economics]. / La réhabilitation respiratoire à domicile: données de la littérature, aspects pratiques et médico-économiques.

INTRODUCTION: Pulmonary rehabilitation is an established part of the management of chronic obstructive airway disease. For longer-term effects, extending rehabilitation into domiciliary care settings may be necessary. There are few studies evaluating precisely this modality of management in a home setting. STATE OF THE ART: This review analyses the current literature on home based rehabilitation. The benefits of pulmonary rehabilitation, the practical aspects of its application, and its advantages and limitations are detailed. The few data on economic aspects of home rehabilitation are also discussed. PERSPECTIVES: Home-based pulmonary rehabilitation is effective with positive short-term effects on quality of life, breathlessness and effort tolerance. Its practical application needs to be defined. CONCLUSION: Home-based pulmonary rehabilitation appears to be an effective intervention in patients with COPD but more studies are necessary to evaluate it fully.

Dissemination of CTX-M-type beta-lactamases among clinical isolates of Enterobacteriaceae in Paris, France.

We analyzed 19 clinical isolates of the family Enterobacteriaceae (16 Escherichia coli isolates and 3 Klebsiella pneumoniae isolates) collected from four different hospitals in Paris, France, from 2000 to 2002. These strains had a particular extended-spectrum cephalosporin resistance profile characterized by a higher level of resistance to cefotaxime and aztreonam than to ceftazidime. The bla(CTX-M) genes encoding these beta-lactamases were involved in this resistance, with a predominance of bla(CTX-M-15). Ten of the 19 isolates produced both TEM-1- and CTX-M-type enzymes. One strain (E. coli TN13) expressed CMY-2, TEM-1, and CTX-M-14. bla(CTX-M) genes were found on large plasmids. In 15 cases the same insertion sequence, ISEcp1, was located upstream of the 5' end of the bla(CTX-M) gene. In one case we identified an insertion sequence designated IS26. Examination of the other three bla(CTX-M) genes by cloning, sequencing, and PCR analysis revealed the presence of a complex sul1-type integron that includes open reading frame ORF513, which carries the bla gene and the surrounding DNA. Five isolates had the same plasmid DNA fingerprint, suggesting clonal dissemination of CTX-M-15-producing strains in the Paris area.