[Atypical Sézary syndrome in a young subject]. / Syndrome de Sézary atypique chez un sujet jeune.

INTRODUCTION: Sézary syndrome accounts for 5% of cutaneous T-cell lymphomas, with mean age of onset of 60 years. Erythroderma associated with palmoplantar keratoderma and lymphadenopathy is the usual clinical presentation, but the disease has potentially confusing polymorphic clinical features. PATIENTS AND METHODS: We report the case of a 27-year-old patient with no notable disease history, presenting generalized non-pruritic dermatosis for 3 months, with erythema and papules, and follicular distribution, localized to the limbs, the trunk and the face. Palmoplantar keratoderma was associated with acral edema. The clinical presentation was initially evocative of pityriasis rubra pilaris. Laboratory tests showed hyperlymphocytosis with Sézary cells in the blood. A diagnosis of grade IVA Sézary syndrome was made based on the skin biopsy results and the PET scan. Screening for KIR3DL2 on T-cells in blood was positive. Extracorporeal photochemotherapy was initiated but cutaneous relapse occurred, leading to combined treatment with bexarotene, which proved ineffictive. Despite numerous chemotherapies (cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone, then dexamethasone, oxaliplatin and cytarabine, associated with brentuximab, vedotin, and, ultimately, clofarabine and endoxan), the patient died after 9 months. DISCUSSION: Our case illustrates an atypical clinical presentation of cutaneous lymphoma in a young patient. With a fatal outcome in 9 months despite 5 different lines of treatment, our case highlights the aggressive nature of Sézary syndrome as well as the difficulties involved in treating this disease. CONCLUSION: A diagnosis of Sézary syndrome must be considered in the event of atypical dermatosis in patients of all ages. The presence of lymphomatous clonal cells and Sézary cells in the blood, immunophenotyping of lymphocytes in blood and marrow, and a second reading of the cutaneous biopsy results enabled us to make a diagnosis of Sezary syndrome.

[Monoclonal gammopathies of undetermined significance do not systematically require a specialized consultation]. / Les gammapathies monoclonales de signification indéterminée ne nécessitent pas systématiquement un recours à une consultation spécialisée.

INTRODUCTION: Monoclonal gammopathy of undetermined significance (MGUS) is a frequent entity in the general population. The incidence rate of fortuitous discovery of a monoclonal component in asymptomatic patients is increasing nowadays. The majority of MGUS is being addressed to a hematologist for diagnosis or follow-up by their generalist practitioners. The management of MGUS consists of a clinical and biological surveillance as per published and validated international guidelines available for MGUS diagnosis and follow-up. MGUS thus may not necessarily need a specialized consultation and follow-up in a hematology ward, as we believe it could be performed by generalist practitioners. METHODS: We studied 190 patients addressed to our hematology department of Lille for diagnosis or follow-up of MGUS. RESULTS: Among the patients, 9.5% developed a malignant hemopathy (multiple myeloma or Waldenström macroglobulinemia). Among patients diagnosed with MGUS of IgG isotype and a monoclonal component <15 g/L, 96.2% showed no pejorative outcome: these represent simple and routine prognostic factors that can be assessed at diagnosis in order to predict the risk of progression. Those patients could have easily been followed by their generalist practitioner from the diagnosis of MGUS. CONCLUSION: A specialist's consultation would still be recommended for patients with pejorative factors at diagnosis, or if a clinical or biological event that could suggest progression occurs during follow-up, or in case of MGUS with complication, in which cases patients would need a specialized management in a hematology department.

Impact of alginate type and bead diameter on mass transfers and the metabolic activities of encapsulated C3A cells in bioartificial liver applications.

Liver-assist devices have been developed in the last few decades to support patients with liver failure on the road to recovery or transplantation. Fluidised bed bio-artificial livers--where liver cells are encapsulated within alginate beads--appear to be a valuable alternative to hollow fibre devices for improving mass transfers and enhancing treatment efficacy. This approach nevertheless deserves optimization in terms of bead production. The aim of this study was to investigate the impact of alginate type and of two bead diameters (1000 µm and 600 µm) on mass transfers within beads and on the biological functions of encapsulated C3A cells. After assessing the effect of the encapsulation process on bead quality, we investigated cell viability and metabolic activities (ammonia, albumin, alpha-fetoprotein synthesis and glucose consumption). They were successfully maintained over 48 h within fluidised bed bioreactors, independently of alginate type and bead diameter. Mass transfers were not significantly influenced by the latter parameters. Finally, suggestions are made for improving the entrapment process as a means of enhancing the treatment efficiency of the fluidised bed bioartificial liver.

Basal insulin dose in 40 type 1 diabetic patients remains stable 1 year after educational training in flexible insulin therapy.

AIM: Basal insulin dose (BID) determination is the key to successful flexible insulin therapy (FIT). As our hypothesis was that BID changes over time, the primary objective of the present study was to determine the changes in BID 1 year after a therapeutic educational programme on FIT. METHODS: This single-centre retrospective study recruited the first 40 type 1 adult diabetic patients undergoing an educational FIT programme, which was conducted over a 4-day hospital stay and included a carbohydrate-fasting test. RESULTS: Patients' BIDs decreased between Day 0 and Day 4 after the programme (0.31±0.11IU/kg/day vs 0.27±0.09IU/kg/day; P<0.0001), and was increased at 1 year (0.29±0.09IU/kg/day; P=0.004). There was no significant variation in prandial insulin requirements. A tendency toward a reduction in HbA(1c) was observed at 1 year (8.3±1.4% vs 8.1±1.6%; P=0.075), with a decrease by more than 0.5% in 37.5% of patients. Body weight increased at 1 year (66.9±10.4 kg vs 68.1±10.7 kg; P=0.003), and the gain was greater than 5% in 7.5% of patients. Frequency of mild hypoglycaemia either remained stable (40%) or decreased (30%). Only nine patients (baseline HbA(1c) 8.03±1.7%, baseline BID 0.27±0.09IU/kg/day) had BID increases more than 20%, with no changes in prandial insulin requirements and no distinctive phenotype. Baseline HbA(1c), and BID have an impact on the BID at 1 year of approximately 0.3IU/kg/day in most patients. CONCLUSION: The stability of BID over 1 year, with values close to 0.3IU/kg/day associated with a trend towards improvement in HbA(1c), reduction in the frequency of mild hypoglycaemic episodes and absence of major weight gain, supports the relevance of FIT educational training.

Tests for determining in-use concentrations of antibiotics and disinfectants are based on entirely different concepts: "resistance" has different meanings.

There are concerns that more extensive application of disinfectants in the food industry could result in increased resistance of bacteria to antibiotics and that therapeutic failure could ensue. This paper highlights the differences in application and mode of action between antibiotics in human or animal medicine and disinfectants in the food industry. It describes the completely different methods used to determine in-use concentrations in the two contexts. It points out that the minimum inhibitory concentration (MIC) is never the concentration at which disinfectants should be applied. It also discusses erroneous conclusions that may be drawn when the failure of therapy or disinfection is attributed to intrinsic properties of the molecules rather than to misuse of antibiotics or disinfectants. The paper suggests that the intended meaning of the word "resistance" be carefully defined in scientific articles with due reference to the measurement mentioned in the abstract and possibly reflected in the title. It also suggests that in matters of disinfection the word "resistance" be preferred when the phenomenon being studied is killing and "tolerance" when it is the adaptation to inhibitory concentrations.

Artificial and bioartificial liver devices: present and future.

Liver failure is associated with high morbidity and mortality without transplantation. There are two types of device for temporary support: artificial and bioartificial livers. Artificial livers essentially use non-living components to remove the toxins accumulated during liver failure. Bioartificial livers have bioreactors containing hepatocytes to provide both biotransformation and synthetic liver functions. We review here the operating principles, chemical effects, clinical effects and complications of both types, with specific attention paid to bioartificial systems. Several artificial support systems have FDA marketing authorisation or are CE labelled, but the improvement they provide in terms of patient clinical outcome has not yet been fully demonstrated. At present, different bioartifical systems are being investigated clinically on the basis of their promises and capacity to provide and replace most liver functions. However, important issues such as cost, cell availability, maintenance of cell viability and functionality throughout treatment, and regulatory issues, as well as difficult challenges, including implementing cell-housing devices at the patient's bedside on an emergency basis, have delayed their appearance in intensive care units and on the market. Bioreactors are, nevertheless, when combined with artificial components, a pragmatic approach for future treatment of liver failure.

Comparative evaluation of biofilm formation and tolerance to a chemical shock of pathogenic and nonpathogenic Escherichia coli O157:H7 strains.

Seven Escherichia coli O157:H7 strains, three pathogenic (including epidemic EDL933 and Sakai) and four nonpathogenic (including mutants of EDL933 and Sakai), were compared to find a model strain to avoid the use of European third-class biological agents in biofilm studies. Comparison was performed on attached populations reached at the end of growth in eight environmental conditions defined as the combinations of three two-level factors: (i) culture medium composed of meat exudate and glucose-supplemented minimal salts medium (MSM), (ii) growth temperatures of 15 and 25 degrees C, and (iii) materials of stainless steel and polyurethane. The influence of each of these four factors (strain, medium, temperature, and material) often depended on the level of at least one of the others. Exudate produced attached populations that were larger than or similar to those obtained with MSM, except for EDL933 mutant at 15 degrees C. When exudate led to larger populations than did MSM, the highest differences of up to 1.8 log CFU/cm2 were observed with the nonepidemic strains grown at 25 degrees C. Populations of these strains were not significantly different in any of the conditions studied, but they were different from the epidemic strains in some conditions. No nonpathogenic mutant was representative of its parental strain. Furthermore, the Sakai mutant biofilm was significantly more reduced than its parental strain was after chemical shock. It is therefore not possible to find a surrogate of either EDL933 or Sakai, and it is advisable that main results be validated on a pathogenic strain whenever nonpathogenic strains are used.

Comparative evaluation of methods for counting surviving biofilm cells adhering to a polyvinyl chloride surface exposed to chlorine or drying.

AIM: To compare techniques for assessing biofilm populations previously subjected, or not, to inimical treatment by chlorine or drying. METHODS AND RESULTS: Four sonication treatments and swabbing were compared on Salmonella Typhimurium or Pseudomonas fluorescens biofilms grown on polyvinyl chloride (PVC). The apparatuses emitting the highest ultrasound energy were the most efficient except on Salm. Typhimurium biofilms subjected to drying: a lethal effect, leading to an underestimation of at least 1.5 log (CFU cm(-2)) was observed with the more aggressive treatment. The differences between the highest count and the swabbing counts ranged from 0.3 log (CFU cm(-2)) (untreated Salm. Typhimurium) to 1.7 log (CFU cm(-2)) (chlorine treated Ps. fluorescens). Impedance measurements, used to assess populations without detaching any cells showed that the calibration curves that were built up from data obtained with suspended cells plus PVC slides were not appropriate. CONCLUSIONS: High energy ultrasound techniques designed either for in vitro or in situ studies proved efficient in assessing the number of attached CFU. However, the right treatment duration has to be carefully established before using high energy ultrasound techniques. SIGNIFICANCE AND IMPACT OF THE STUDY: The effectiveness of a cleaning and disinfection regime inferred from data obtained after swabbing may be greatly underestimated.

The place of adsorption and biochromatography in extracorporeal liver support systems.

Artificial and bioartificial liver devices aim at replacing some or all liver functions in the cases of end stage or fulminant disorders. Among all of its function, liver plays a key role in detoxification of substances that are hydrosoluble or bound to albumin. In this paper, the authors first reviewed the requirements for temporary liver support, then the adsorption-based systems that can be found on the market and finally propose new applications of biochromatography using perfusion-based bioartificial systems.

Beneficial effects due to increasing blood and plasma viscosity.

Increased plasma and blood viscosity are usually associated with pathological conditions; however there are several situations in which the elevation of both parameters results in increased perfusion and the lowering of peripheral vascular resistance. In extreme hemodilution blood viscosity is too low and insufficient to maintain functional capillary density, a problem that in experimental studies is shown to be corrected by increasing plasma viscosity up to 2.2 cP. This effect is mediated by Nitric oxide (NO) production via restoration of shear stress at the endothelium as shown by microelectrode perivascular measurements of NO concentration. Moderate elevations of blood viscosity by increasing hematocrit (approximately 10% of baseline) result in reductions of blood pressure by 10 mmHg of baseline. This effect is also NO mediated since it is absent after N-nitro-L-arginine methyl ester (L-NAME) treatment and in endothelial NO synthase deficient mice. These results show that the rheological properties of plasma affect vessel diameter in the microcirculation leading to counterintuitive responses to the increase in viscosity.

[Is early treatment of infants at risk of spastic diplegia warranted?]. / La prise en charge précoce de l'enfant à risque de diplégie spastique est-elle utile? Est-elle opportune?

OBJECTIVE: To test the possible link between first investigation and development of spastic diplegia. METHOD: A long-term retrospective study was carried out in the Neonatal Medicine Department of Arras Hospital, the C.A.M.S.P. of that town and with corresponding therapists. RESULTS: The study undertaken from January 1, 1991, to December 31, 1997, involved 56 children suspected of developing spastic diplegia and requiring a specialized course of treatment during the evolution of disease. In 32, evolution of disease was favourable, and in 24 spastic diplegia developed. An unfavourable evolution was significantly associated with late intervention of rehabilitation. CONCLUSION: Although few pre- or neonatal factors differentiated the two groups of children in their opposite evolution, haemorrhage during pregnancy and early detection seem to be determining factors in spastic diplegia.

Impact of cleaning and disinfection agents on biofilm structure and on microbial transfer to a solid model food.

AIM: To determine how single cells and microcolonies transfer to food from open surfaces in the meat industry. METHODS AND RESULTS: Biofilms of four bacterial strains isolated from food processing surfaces were established on stainless steel substrates conditioned with meat exudate in the presence or absence of CaCl(2). Image analysis of the biofilms showed that the addition of calcium resulted in an increase of the number and size of microcolonies with two strains: Staphylococcus sciuri and Pseudomonas fluorescens. Image analysis of the biofilms of those two strains grown in the presence of calcium was performed before and after contacts with tryptone soya agar as a solid model food. For the biofilms treated or not with a chlorinated alkaline agent, where a decrease in surface coverage occurred, it was accompanied by a decrease in the percentage of the coverage accounted for by microcolonies (P(m)). Attachment strength was greater for P. fluorescens than for S. sciuri. When the P. fluorescens biofilms were treated with a solution containing glutaraldehyde, the contacts did not modify their structure. By contrast, their treatment with chlorinated alkaline resulted, after contacts, in the smallest coverage and P(m). With S. sciuri, a decrease in coverage after contacts always occurred and was the greatest for the untreated biofilms. CONCLUSIONS: After contacts between biofilms and a solid model food, microcolonies were preferentially detached compared with single cells. A chlorinated alkaline product either decreased biofilm attachment strength (P. fluorescens) or unexpectedly increased it (S. sciuri), whereas a glutaraldehyde-based disinfectant increased both attachment strength and microcolony cohesion. SIGNIFICANCE AND IMPACT OF THE STUDY: The contaminating potential of a surface depends not only on the level of contamination but also on the nature, structure and history of the contamination.

Ecology of mixed biofilms subjected daily to a chlorinated alkaline solution: spatial distribution of bacterial species suggests a protective effect of one species to another.

Three bacterial strains (Kocuria sp. C714.1, Brevibacterium linens B337.1 and Staphylococcus sciuri CCL101) were grown together on stainless steel and were subjected daily to a commercial alkaline chlorine solution (22 mg l-1 of free chlorine, pH 11) over a period of 4 weeks. After the daily chemical shock, culture madia [1:20 dilution of tryptic soy broth (TSB-YE/20) or diluted whey] was deposited on the biofilms. The chemical shocks led first to a drop in the culturable population, followed by an increase and finally stabilization at around 106-107 CFU cm-2 by day 11 of the experiment. These changes in the microbial population can be attributed to a decreasing susceptibility to the antimicrobial agent with biofilm age, and to the consumption of free chlorine by biofilm exoproteins. The microbial composition appeared to be linked to the free chlorine concentration that depended on exoprotein production. At the end of the experiment, exoprotein production was greater for biofilms grown in TSBYE/20 than in whey. As a consequence, biofilms grown in whey did not neutralize the chlorine and the dominant strain was the one having the highest resistance to chlorine: K. varians. When biofilm were grown in TSBYE/20, chlorine was neutralized and the dominant strain was the one having the highest growth rate: S. sciuri. The presence of chlorine may also explain the distribution of S. sciuri cells as a ring around Kocuria sp. microcolonies. When chlorine was totally consumed by the biofilm during the chemical shock, S. sciuri was no longer grouped around Kocuria sp. microcolonies but was evenly scattered over the substratum as single cells or in small clusters, as it was before any chemical treatment. These findings strongly suggest protection of S. sciuri by Kocuria sp. microcolonies against the chlorinated solution. This phenomenon, added to the low susceptibility phenotype of the biofilm cells, could at least partly explain the survival of microbial cells in an adverse environment.

Gastrostomy as a decompression technique in children with chronic gastrointestinal obstruction.

BACKGROUND: Percutaneous or surgical insertion of gastrostomy tubes for feeding children has been well described. However, there is no report of percutaneous gastrostomy for chronic decompression in children with chronic gastrointestinal obstruction. The objective of this study was to evaluate this technique. METHODS: Eighteen gastrostomies were performed for gastrointestinal decompression in children. The patients ranged in age from 2 to 125 months (median: 15.5), and all had prolonged hospital stays for severe disease: severe gastroparesis and/or duodenal dysmotility (n = 8), duodenal stenosis (n = 2), chronic intestinal pseudo-obstruction (n = 4), enterocolitis (n = 2), and metastatic abdominal carcinomatosis (n = 2). The duration of symptoms before gastrostomy placement ranged from 0.5 to 44 months (median: 2), with major symptoms including epigastric pain, early satiety, nausea, vomiting, and bloating. RESULTS: The goals of gastric decompression and removal of the nasogastric tube were achieved in all patients, and all had significant relief of both nausea and emesis. Oral intake of liquids and soft foods was possible in 17 of 18 of the children. The tubes were kept in place for a median of 22.5 months (range, 2-73). There was neither long-term morbidity nor mortality associated with the presence of the tube. Seventeen patients returned home with gastric decompression and cyclic parenteral nutrition, two of them for terminal care. Six patients died. In all patients, gastrostomy was used throughout and did not contribute to the death of the patients. For seven children, tubes were removed because of resolution of small bowel or gastric outlet obstruction. CONCLUSIONS: Gastrostomy is an efficient and well-tolerated method of achieving long-term gastric decompression in children with abdominal obstruction not amenable to surgery and/ or resistant to medical treatment.

Pump battery assessment: cold, old, or dead!

Intraspinal drug delivery systems are becoming increasingly utilized for the management of patients with pain or spasticity. Numerous potential complications associated with the use of this technology have previously been described in the literature. We have had experience with a new complication of the internal alarm being triggered by the instillation of cold solution into the pump resevoir. This new finding could have implications for patients with respect to unnecessary reevaluations of the pump, or possible premature scheduling of pump replacement surgery.

Use of an enzyme-linked lectinsorbent assay to monitor the shift in polysaccharide composition in bacterial biofilms.

An enzyme-linked lectinsorbent assay (ELLA) was developed for quantification and characterization of extracellular polysaccharides produced by 1- and 4-day biofilms of 10 bacterial strains isolated from food industry premises. Peroxidase-labeled concanavalin A (ConA) and wheat germ agglutinin (WGA) were used, as they specifically bind to saccharide residues most frequently encountered in biofilms matrices: D-glucose or D-mannose for ConA and N-acetyl-D-glucosamine or N-acetylneuraminic acid for WGA. The ELLA applied to 1- and 4-day biofilms colonizing wells of microtiter plates was able to detect that for Stenotrophomonas maltophilia and to a lesser extent Staphylococcus sciuri, the increase in production of exopolysaccharides over time was not the same for sugars binding with ConA and those binding with WGA. Differences in extracellular polysaccharides produced were observed among strains belonging to the same species. These results demonstrate that ELLA is a useful tool not only for rapid characterization of biofilm extracellular polysaccharides but also, in studies of individual strains, for detection of changes over time in the proportion of the exopolysaccharidic component within the polymeric matrix.

Limitation of adhesion and growth of Listeria monocytogenes on stainless steel surfaces by Staphylococcus sciuri biofilms.

The adhesion and subsequent development of Listeria monocytogenes on stainless steel was studied in the absence and in the presence of a Staphylococcus sciuri biofilm. In the three growth media studied, the percentage of adherent cells was reduced to nearly the same extent by the presence of 1-day biofilms of Staph. sciuri for the two strains of L. monocytogenes studied. One-day biofilms of Staph. sciuri exhibited the same exopolysaccharide content per square centimetre, although they colonized from 3.5 to 35% of the stainless steel depending on the growth media. This suggests that extracellular substances rather than cell-to-cell interactions were involved in the decreased adhesion. After 3 days of culture, Staphylococcus biofilms prevented the adherent L. monocytogenes population from increasing within the biofilm, leading to an average logarithmic cfu difference of 0.9-2.7 between the pure and mixed culture. A competition for nutrients by Staph. sciuri was observed in one of the three media. A role for extracellular polysaccharides produced by the Staphylococcus biofilm in preventing the adhesion of L. monocytogenes and in modifying the balance existing between its planktonic and biofilm phase is hypothesized. A higher proportion of L. monocytogenes cells was observed in the planktonic phase in mixed cultures, suggesting that the extracellular substances produced by Staph sciuri biofilms and involved in the decreased adhesion of L. monocytogenes could modify the balance existing between planktonic and biofilm populations. In addition, co-cultures of L. monocytogenes and Staph. sciuri in broth showed competition for nutrients for Staph. sciuri in one of the three media.

[Health costs associated with the diabetic foot in developed countries.A plea for the creation of health care networks]. / Coûts de santé liés aux lésions du pied chez les diabétiques dans les pays développés. Plaidoyer pour la création de structures de soins adaptées.

COST OF DIABETIC FOOT: A limited number of epidemiological and economical studies on diabetic foot in France is available. Studies conducted in other countries, namely USA, Netherlands, UK and especially Sweden, have evidenced major direct and indirect costs that generally are underestimated in overall economical cost of diabetes forecast. The rapid increase of diabetes prevalence throughout the world, combined with diabetic population aging, allows to speculate that this situation may dramatically worsen in the future. In order to reduce the economical and human burden of this complication, it is an urgent public health necessity in France to set multidisciplinary organisations, dealing with both in-patient care, which importance should be decreasing, and out-patient care, as well as prevention and foot care networks. The swedish experience figures an interesting model for our healthcare system.

Behaviour of L. monocytogenes in an artificially made biofilm of a nisin-producing strain of Lactococcus lactis.

The survival of Listeria monocytogenes in a binary biofilm with a bacteriocin producer (Lactococcus lactis CNRZ 150) was investigated. Two situations were simulated: in the first, L. monocytogenes was deposited on a 1-day biofilm of Lactococcus lactis (deferred adhesion); in the second, L. monocytogenes was simultaneously mixed with Lact. lactis (simultaneous adhesion). Biofilms were cultivated in tryptic soy broth supplemented with 6 g l(-1) of yeast extract (TSB-YE) and L. monocytogenes counts were followed for 48 h, both in co-culture with Lact. lactis and in pure culture. The influence of the mode of inoculation of L. monocytogenes (deferred or simultaneous adhesion) into the Lact. lactis biofilm, the size of the L. monocytogenes inoculum and the replacement of the culture medium at 20-24 h on the survival of L. monocytogenes was studied. Results showed that the antilisterial activity of the Lact. lactis started within the first 6 h of the deposition of L. monocytogenes. The log cycle reduction rate in number of L. monocytogenes in the mixed biofilm (compared to the pure biofilm) was greatly dependent on the inoculum size: when the smallest inoculum was used to colonise stainless steel coupons (10(6)-10(7) CFU ml(-1)), the log cycle reduction was greater and L. monocytogenes was not detected after t = 10 h (simultaneous adhesion) and t = 24 h (deferred adhesion) in the adherent population as well as in the planktonic population. On the other hand, in the case of a greater supply of L. monocytogenes (10(8) CFU ml(-1)), the results showed that the early reduction of L. monocytogenes counts was relatively slow and was followed by a stabilisation of the population, leading to the establishment of a great number of resident cells in the biofilm (10(5) to 106 CFU cm(-2)). This population level was maintained during the 48 h of experimentation and replacement of the culture media with fresh medium at t = 22 h (simultaneous adhesion) or t = 24 h (deferred adhesion) did not modify the level of the population of L. monocytogenes within the biofilm.