First synthesis of silicon nanocrystals in amorphous silicon nitride from a preceramic polymer.

We report the first synthesis of silicon nanocrystals embedded in a silicon nitride matrix through a direct pyrolysis of a preceramic polymer (perhydropolysilazane). Structural analysis carried out by XRD, XPS, Raman and TEM reveals the formation of silicon quantum dots and correlates the microstructures with the annealing temperature. The photoluminescence of the nanocomposites was investigated by both linear and nonlinear measurements. Furthermore we demonstrate an enhanced chemical resistance of the nitride matrix, compared to the typical oxide one, in both strongly acidic and basic environments. The proposed synthesis via polymer pyrolysis is a striking innovation potentially allowing a mass-scale production nitride embedded Si nanocrystals.

The gap between scientific evidence and clinical practice: 5-aminosalicylates are frequently used for the treatment of Crohn's disease.

BACKGROUND: There is uncertain evidence of effectiveness of 5-aminosalicylates (5-ASA) to induce and maintain response and remission of active Crohn's disease (CD), and weak evidence to support their use in post-operative CD. AIM: To assess the frequency and determinants of 5-ASA use in CD patients and to evaluate the physicians' perception of clinical response and side effects to 5-ASA. METHODS: Data from the Swiss Inflammatory Bowel Disease Cohort, which collects data since 2006 on a large sample of IBD patients, were analysed. Information from questionnaires regarding utilisation of treatments and perception of response to 5-ASA were evaluated. Logistic regression modelling was performed to identify factors associated with 5-ASA use. RESULTS: Of 1420 CD patients, 835 (59%) were ever treated with 5-ASA from diagnosis to latest follow-up. Disease duration >10 years and colonic location were both significantly associated with 5-ASA use. 5-ASA treatment was judged to be successful in 46% (378/825) of treatment episodes (physician global assessment). Side effects prompting stop of therapy were found in 12% (98/825) episodes in which 5-ASA had been stopped. CONCLUSIONS: 5-Aminosalicylates were frequently prescribed in patients with Crohn's disease in the Swiss IBD cohort. This observation stands in contrast to the scientific evidence demonstrating a very limited role of 5-ASA compounds in the treatment of Crohn's disease.

Efetividade do EDTA 17% na remo??o da smear layer e da medica??o intracanal de hidr?xido de c?lcio das paredes dos canais radiculares: parte II / Effect of 17% EDTA on removal of canal wall smear layer and calciumhydroxide dressing: part II

Objective: the aim of this study was to evaluate, by scanning electron microscopy, the effectiveness of 17% EDTA on removal of canal wall smear layer and calcium hydroxide dressing in different thirds of root canal. Methods: Ttwenty-four premolars were instrumented in the cervical and middle thirds using Gates-Glidden drills. At the working length, the canal was widened up to # 35 file, followed by scaling up to file # 50. After instrumentation, the teeth were divided into four groups according to the treatment received: GI - irrigation performed with 5 ml of NaOCl 2.5 % ; GII - irrigation with 5 ml of 17% EDTA for 2 and a half minutes , submitted to agitation with file # 15, followed by irrigation with 5 ml of 2.5% NaOCl ; GIII - irrigation with 5 ml of NaOCl 2.5% , drying , application of temporary dressing of Ca (OH )2 with propylene glycol and sealing. After 5 days , removing the sealing irrigation with 5 ml of 17% EDTA for 2 and a half minutes , submitted to agitation with file # 15, followed by a final flush with 5 ml of 2.5% NaOCl ; GIV - irrigation with 5 ml of 17% EDTA for 2 and a half minutes , submitted to agitation with file # 15 , followed by irrigation with 5 ml of 2.5% NaOCl , drying and after use of the medication in Ca (OH )2 with the sealing and propylene glycol which was removed after 5 days performing the irrigation with 5 ml of 17% EDTA for 2 and a half minutes , submitted to agitation with file # 15, followed by using 5 ml 2.5% NaOCl . Next, the teeth were prepared and taken to the scanning electron microscope. Results: The images revealed: Group I - a marked presence of smear layer in all three thirds, Group II - removal of almost all of the smear layer in the cervical third and removal of large quantity in the middle third, whereas in the apical third a large quantity of smear layer still remained however, in comparison with the other groups, this was shown to be cleaner; Group III - in the three thirds, the presence of smear layer was observed, which was shown to be much less compacted than that observed in Group 1; Group IV- in all the thirds there was reduction of smear layer and Ca(OH)2-based medication, and presence of several unobstructed dentinal tubules could be observed, demonstrating the second best result observed. Conclusion: It could be concluded that the use of 17% EDTA favored removal of the smear layer and intracanal medication residues in all thirds of the root canal.

Objetivo: Avaliar atrav?s de Microscopia Eletr?nica de Varredura, a efic?cia do EDTA a 17% na remo??o da smear layer e da medica??o de hidr?xido de c?lcio nos diferentes ter?os do canal radicular. M?todos: Vinte e quatro pr?-molares foram instrumentados nos ter?os cervical e m?dio utilizando-se brocas Gates-Glidden. No comprimento de trabalhorealizou-se o alargamento at? a lima #35 seguido do escalonamento at? a lima #50. Ap?s, os dentes foram divididos em quatro grupos de acordo como tratamento recebido: GI - irriga??o realizada com 5 ml de hipoclorito de s?dio a 2,5%; GII - irriga??o com 5 ml de EDTA 17%, durante 2 minutose meio, submetidos a agita??o com a lima #15, seguidos de uma irriga??o com 5 ml de NaOCl a 2,5%; GIII - irriga??o com 5 ml de hipoclorito des?dio a 2,5%, secagem, aplica??o de medica??o intracanal de Ca(OH)2 associado ao propilenoglicol e selamento, ap?s 5 dias, remo??o do selamento, irriga??o com 5 ml de EDTA 17%, durante 2 minutos e meio, submetidos a agita??o com a lima #15, seguida de irriga??o final com 5 ml de NaOCl a 2,5%; GIV - irriga??o com 5 ml de EDTA 17%, durante 2 minutos e meio, submetidos a agita??o com a lima #15, seguidos de uma irriga??o com 5 ml de NaOCl a 2,5%, secagem e ap?s o uso da medica??o intracanal de Ca(OH)2 associado ao propilenoglicol e selamento que foi removido ap?s 5 dias realizando-se a irriga??o com 5 ml de EDTA 17%, durante 2 minutos e meio, submetidos a agita??o com a lima #15, seguida da utiliza??o de 5 ml de NaOCl a 2,5%. A seguir, os dentes foram preparados e levados ao microsc?pio eletr?nico de varredura. Resultados: As imagens revelaram: grupo I - presen?a marcante de smear layer nos tr?s ter?os; grupo II - nota-se a menor quantidade de smear layer no ter?ocervical e m?dio enquanto no apical h? presen?a mais marcante; grupo III- no ter?o cervical e apical h? presen?a de smear layer compactada nas paredes do canal e o aspecto mais disperso da medica??o enquanto no ter?o m?dio nota-se presen?a da medica??o no interior dos canal?culos; grupo IV- em todos os ter?os houve redu??o da smear layer e da medica??o e a presen?a de v?rios canal?culos dentin?rios desobstru?dos.Conclus?o: Pode-se concluir que o uso do EDTA a 17% favoreceu a remo??o da lama dentin?ria e dos res?duos da medica??o intracanal em todos os ter?os do canal radicular.

Identification of human tear fluid biomarkers in vernal keratoconjunctivitis using iTRAQ quantitative proteomics.

BACKGROUND: Understanding and treating vernal keratoconjunctivitis (VKC) has been a challenge because the pathogenesis is unclear and antiallergic therapy often unsuccessful. The aim of the study was to analyze peptide profiles in human tears using mass spectrometry to elucidate compositional differences between healthy subjects and patients affected by VKC. METHODS: Tears were collected from healthy subjects and VKC patients. Digested samples were treated with iTRAQ (isobaric tag for relative and absolute quantitation). Separation of tryptic peptides was realized using a MicroHPLC interfaced with a microfraction collector. MS and MS/MS mass spectra were performed using a MALDI TOF/TOF 4800 Applied Biosystem spectrometer. Protein Pilot™ software with Paragon™ algorithm v4.1.46 or GPS™ with Mascot engine was used as search engines with SwissProt or IPI human as the databases. RESULTS: A significant number of peptides were examined, and 78 proteins were successfully identified. In all VKC samples, levels of serum albumin, transferrin, and hemopexin were found up to 100 times higher than control tear levels and correlated to the severity of disease. Hemopexin, transferrin, mammaglobin B, and secretoglobin 1D were found significantly over-expressed in VKC samples compared with the control samples. Tear samples from patients treated with topical cyclosporine or corticosteroids showed a dramatic reduction in these protein levels. CONCLUSIONS: LC MALDI MS and isobaric tag for relative and absolute quantitation technique may be useful in the quantitative and qualitative characterization of the peptidoma of human tears. These techniques may identify target proteins to be used in the diagnosis and management of VKC and other inflammatory ocular surface conditions.

Effects of fructose and glucose overfeeding on hepatic insulin sensitivity and intrahepatic lipids in healthy humans.

OBJECTIVE: To assess how intrahepatic fat and insulin resistance relate to daily fructose and energy intake during short-term overfeeding in healthy subjects. DESIGN AND METHODS: The analysis of the data collected in several studies in which fasting hepatic glucose production (HGP), hepatic insulin sensitivity index (HISI), and intrahepatocellular lipids (IHCL) had been measured after both 6-7 days on a weight-maintenance diet (control, C; n = 55) and 6-7 days of overfeeding with 1.5 (F1.5, n = 7), 3 (F3, n = 17), or 4 g fructose/kg/day (F4, n = 10), with 3 g glucose/kg/day (G3, n = 11), or with 30% excess energy as saturated fat (fat30%, n = 10). RESULTS: F3, F4, G3, and fat30% all significantly increased IHCL, respectively by 113 ± 86, 102 ± 115, 59 ± 92, and 90 ± 74% as compared to C (all P < 0.05). F4 and G3 increased HGP by 16 ± 10 and 8 ± 11% (both P < 0.05), and F3 and F4 significantly decreased HISI by 20 ± 22 and 19 ± 14% (both P < 0.01). In contrast, there was no significant effect of fat30% on HGP or HISI. CONCLUSIONS: Short-term overfeeding with fructose or glucose decreases hepatic insulin sensitivity and increases hepatic fat content. This indicates short-term regulation of hepatic glucose metabolism by simple carbohydrates.

Endocytosis and intracellular localisation of type 1 ribosome-inactivating protein saporin-s6.

Saporin-S6 is a single-chain ribosome-inactivating protein (RIP) that has low toxicity in cells and animals. When the protein is bound to a carrier that facilitates cellular uptake, the protein becomes highly and selectively toxic to the cellular target of the carrier. Thus, saporin-S6 is one of the most widely used RIPs in the preparation of immunoconjugates for anti-cancer therapy. The endocytosis of saporin-S6 by the neoplastic HeLa cells and the subsequent intracellular trafficking were investigated by confocal microscopy that utilises indirect immunofluorescence analysis and transmission electron microscopy that utilises a direct assay with gold-conjugated saporin-S6 and an indirect immunoelectron microscopy assay. Our results indicate that saporin-S6 was taken up by cells mainly through receptor-independent endocytosis. Confocal microscopy analysis showed around 30% co-localisation of saporin-S6 with the endosomal compartment and less than 10% co-localisation with the Golgi apparatus. The pathway identified by the immunofluorescence assay and transmission electron microscopy displayed a progressive accumulation of saporin-S6 in perinuclear vesicular structures. The main findings of this work are the following: i) the nuclear localisation of saporin-S6 and ii) the presence of DNA gaps resulting from abasic sites in HeLa nuclei after intoxication with saporin-S6.

Effect of red pepper on symptoms of irritable bowel syndrome: preliminary study.

BACKGROUND: Abdominal pain, that characterizes irritable bowel syndrome (IBS) together with bloating and disordered defecation, is mainly related to a visceral hypersensitivity due to an increase of TRPV(1) nociceptive nerve fiber activity. AIM: As capsaicin contained in red pepper is able to desensitize the TRPV(1) fibres, we evaluated whether the red pepper oral administration can decrease the symptoms of visceral hypersensitivity in IBS patients. METHODS: The study was performed on 50 patients with IBS diagnosed following Rome II criteria. After a 2-week washout period, 23 patients were planned to receive 4 pills/day, for 6 weeks randomly and in a double blind manner, each containing 150 mg of red pepper powder with a coat that dissolves in the colon, and 27 patients placebo. The patients scored each day in a diary the abdominal pain and bloating intensities following the 5-point Likert scale. The weekly symptom mean scores and the final patient subjective evaluation on treatment effectiveness were statistically compared among groups and intra-groups with appropriate tests. RESULTS: Eight patients dropped from the study: 6 in the red pepper group for abdominal pain and 2 in the placebo group. In 8 patients, the pills were reduced to 2/day, because of the abdominal pain at the onset of treatment. The intra-group comparisons showed that in patients taking red pepper the abdominal pain and bloating mean score values of the last weeks of treatment were significantly improved with respect to pre-treatment values, unlike patients taking placebo. The final patient subjective evaluation on the treatment effectiveness showed that red pepper group scored significantly better than placebo. CONCLUSIONS: The results of this preliminary study indicate that the chronic administration of red pepper powder in IBS patients with enteric-coated pills was significantly more effective than placebo in decreasing the intensity of abdominal pain and bloating and was considered by the patients more effective than placebo.

Effects of short-term overfeeding with fructose, fat and fructose plus fat on plasma and hepatic lipids in healthy men.

AIMS: The present study aimed to assess the effects of excess fat, fructose and fat-plus-fructose intakes on intrahepatocellular lipid (IHCL). METHODS: Healthy male subjects were studied after an isocaloric diet or a 7-day high-fructose (Fru: +3.5 g fructose/kg fat-free mass/day, +35% energy), high-fat (Fat: +30% energy as saturated-fat) or high-fructose, high-fat diet (FruFat: +3.5 g fructose/kg fat-free mass/day, +30% energy as fat, +65% total energy). IHCL was measured by (1)H magnetic resonance spectroscopy. RESULTS: All hypercaloric diets increased IHCL (Fru: +16%; Fat: +86%; FruFat: +133%; P<0.05). Very low-density lipoprotein (VLDL) triacylglycerols increased after Fru (+58%; P<0.05), but decreased after Fat (-22%; P<0.05), while no change was observed after FruFat. CONCLUSION: Fat and fructose both increased IHCL, but fructose increased, while fat decreased, VLDL triacylglycerols. However, excess fat and fructose combined had additive effects on IHCL and neutralizing effects on VLDL triglycerides. This suggests that fructose stimulates, while fat inhibits, hepatic VLDL triacylglycerol secretion.

Treatment of gastric emptying delay.

Gastric emptying delay is a rather frequent occurrence that may reveal itself with a broad spectrum of clinical manifestations, from slight dyspeptic symptoms up to alimentary vomiting. Once diagnosed with appropriate examinations, the treatment of this condition may be performed with a variety of means proportionate to the severity of the disease. In the first line there are dietetic measures and pharmacologic aids, that vary from currently available prokinetics drugs, drugs created for other therapeutical purposes, that reveal prokinetic properties, to new classes of prokinetics currently under clinical investigation or clinical trials. In more severe cases of gastroparesis, with vomiting and abdominal pain refractory to prokinetic therapy, other pharmacologic measures can be utilized, such as antiemetic and analgesic drugs. If the medical therapy is insufficient, endoscopic and surgical procedures are available, from the widening of the pyloric ring with botulinum toxin infiltrations or pneumatic dilatation, to the employment of various techniques of gastric electrical stimulation, up to partial or total gastric resection, when any other treatment fails and the patient is kept alive only with partial or total parenteral nutrition.

Cytokines, matrix metalloproteases, angiogenic and growth factors in tears of normal subjects and vernal keratoconjunctivitis patients.

BACKGROUND: To detect the presence of multiple mediators and growth factors in tears of vernal keratoconjunctivitis (VKC) patients with active disease using stationary phase antibody arrays. METHODS: Tears were collected from 12 normal subjects (CT) and 24 active VKC patients. Tears were centrifuged and successively probed using three microwell plate arrays specific for: (i) cytokines: interleukin (IL)-2, IL-4, IL-5, IL-8, IL-10, IL-12, IL-13, interferon-gamma and tumour necrosis factor-alpha; (ii) growth factors: basic fibroblast growth factor (bFGF), platelet-derived growth factor, thrombopoietin, angiopoietin-2, vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), keratocyte growth factor, tissue inhibitor of metalloprotease (TIMP)-1 and heparin-binding epithelial growth factor (HB-EGF) and (iii) matrix metalloprotease (MMP)-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, TIMP-1 and TIMP-2. RESULTS: Interleukin-8 signals were detected in all CT and highly detected in all VKC samples. The Th2-type cytokines, IL-4, IL-5 and IL-10 were detected only in tears of VKC patients. Signals for bFGF, HB-EGF, VEGF and HGF were detected in 41-87% of VKC samples and in few CT samples. Only TIMP-1 and TIMP-2 were found in all normal and patient tear samples, whereas MMP-1, MMP-2, MMP-3, MMP-9 and MMP-10 were highly present in all VKC samples. CONCLUSIONS: Stationary phase antibody array methodology was useful for the screening of various cytokines, growth factors and MMPs in tears. These analyses identified in tears of VKC patients previously unreported factors including MMP-3 and MMP-10 and multiple proteases, growth factors and cytokines, which may all play an important role in the pathogenesis of conjunctival inflammation.

Allergy and the eye.

The eye represents an ideal and frequent site for the allergic reactions. The term 'allergic conjunctivitis' refers to a collection of disorders that affect the lid, conjunctiva and/or cornea. Even though the diagnosis is essentially clinical, local tests such as cytology, conjunctival provocation and tear mediator analysis can be performed. The immunoglobulin E (IgE)-mediated mechanism does not explain completely the severity and the clinical course of chronic allergic ocular diseases such as vernal (VKC) and atopic keratoconjunctivitis (AKC), which are probably also related to T cell-mediated responses, massive eosinophil attraction and activation and non-specific hypersensitivity. An altered balance between T helper type 1 (Th1) and Th2 cells and between Th1- and Th2-types of cytokines is thought to be responsible of the development of ocular allergic disorders. New findings suggest that a wide range of cytokines, chemokines, proteases and growth factors are involved by complex interwoven interactions rather than distinct and parallel pathways. In addition, several non-specific enzymatic systems may be activated during acute and chronic allergic inflammation, thus contributing to the complex pathogenesis of the disease. Current drug treatment for ocular allergy targets the key mechanisms involved in the development of clinical disease: mast cells with mast cell stabilizers, histamine with histamine receptor antagonists and inflammation with corticosteroids, severe inflammation with immunomodulators. None of these agents lacks side effects and none abolishes signs and symptoms completely. New therapeutic strategies are still needed to respond to the complex pathogenesis of severe forms of ocular allergy such as VKC and AKC.

Clinical and biological efficacy of preservative-free NAAGA eye-drops versus levocabastine eye-drops in vernal keratoconjunctivitis patients.

AIMS: This comparative and randomised pilot study assessed the clinical and biological efficacy of Naaxia Sine(R) eye-drops versus levocabastine eye-drops in the treatment of vernal keratoconjunctivitis (VKC). METHODS: Twenty-three VKC patients were randomised and treated bilaterally for 28 days with N-acetyl-aspartyl-glutamate (NAAGA) or levocabastine (LEVO) eye-drops. The primary efficacy variable, overall evolution of eosinophil cationic protein (ECP) tear concentrations, was assessed in a masked fashion on D0, D7 and D28. Clinical symptoms and signs were reported at the same time points. Biological parameters were analysed with a non-parametric rank-based approach. Global tolerance was assessed by the investigator and patient. RESULTS: At all time points, ECP tear levels were significantly reduced in the NAAGA compared with the LEVO group (p = 0.023). Reduction of eosinophil leucocytes and tear lymphocytes was higher not significant in the NAAGA group. The same trend was observed for the evolution of total ocular symptom score. There were no significant differences between treatment groups in the occurrence of adverse effects, except for burning which was more frequent in the LEVO group (p = 0.002). CONCLUSION: The anti-eosinophilic actions of NAAGA were shown by a significant reduction of ECP tear concentrations. A decreased lymphocyte count and an overall improvement of the symptomatology were also noted. Moreover, the tolerability of NAAGA appeared to be better.

Molecular connectivity methods for the characterization of surface energetics of liquids and polymers.

In the topological approach to structure-property relationships, the molecular structure is described in terms of appropriate weighted graphs to which suitable topological parameters, usually known as molecular connectivity indices, can be associated. Molecular connectivity indices are here applied to the prediction of surface free energy and Good-van Oss-Chaudhury acid-base components of organic compounds. To this aim, some quantitative structure-property relationships (QSPRs) are determined, involving both topological indices and group indicator variables of the customary functional group theory. The semiempirical models obtained to appear satisfactory and show significant advantages with respect to the models based on the purely functional group approach.

Obstructive sleep apnoea is improved by a prolonged treatment of gastrooesophageal reflux with omeprazole.

BACKGROUND: Obstructive sleep apnoea has been demonstrated to induce gastrooesophageal reflux through highly negative intrathoracic pressure during the attacks. However, we believe that gastrooesophageal reflux on its part may favour or aggravate the apnoea attacks. AIMS: We investigated whether the treatment of gastrooesophageal reflux with omeprazole is able to decrease apnoea attacks. PATIENTS AND METHODS: Twenty patients (mean age 55.4 years, range 49-73 years; 17 males) with confirmed obstructive sleep apnoea at overnight polysomnography and pathological gastrooesophageal reflux at ambulatory 24-h oesophageal pHmetry were asked to note in a diary the occurrence of apnoea attacks for a basal period of 4 weeks. Subsequently, the patients were randomly and in a double-blind manner treated with omeprazole 20mg (10 patients, group A) or placebo (10 patients, group B) by giving 1 cp 30 min before breakfast and 1 cp 30 min before dinner for another 6 weeks with a diary documentation. The results were averaged weekly and over the entire treatment duration and a statistical comparison was made between the groups and within each group before and after treatment. RESULTS: The mean weekly frequency of apnoea attacks of group A during the entire period of treatment with omeprazole was significantly decreased with respect to the basal period and was significantly lower than that of group B. The weekly frequency of apnoea attacks in group A started to be significantly lower from the third week than the corresponding values of both group B and the basal period, reaching a decrease of about 73% in the sixth week. CONCLUSION: The occurrence of apnoea attacks progressively decreased during the treatment of gastrooesophageal reflux with omeprazole. This fact suggests that gastrooesophageal reflux may play a role in triggering and/or worsening obstructive sleep apnoea.

A novel antireflux device based on magnets.

BACKGROUND: The problem of eliminating gastroesophageal reflux (GER) with simple, effective and devoid of unpleasant side effects procedures is still unresolved. We tried to settle this problem with a magnetic device that should be applied to the distal end of the esophagus. MATERIALS AND METHODS: Two plastoferrite magnets of 2 x 4 x 0.5cm(1) were applied, on the opposite sides of a flaccid polyethylene tube mimicking the physical characteristics of the terminal esophagus. The two magnets attracting themselves compressed the tube, creating an artificial high-pressure zone that divided the tube in two segments. Both segments of the tube were connected to pressure transducers and a polygraph and one of them was connected to a hydraulic pump. The pressure was progressively increased in this segment up to a value sufficient to detach the magnets with consequent flowing of the water in the other segment of the tube. RESULTS: The progressive increase of the pressure in a segment of the tube detached the magnets allowing a free flow into the other segment when the pressure reached an average value of 9.75+/-1.05 mmHg (mean+/-SD). CONCLUSIONS: A couple of magnets clamping a tube with the characteristics of the distal esophagus is able to prevent the passage of liquid with a pressure value near to that of a normal lower esophageal sphincter. This magnetic device could be useful to maintain closed a sphincter unable to prevent gastroesophageal reflux.

Effect of different sterile barrier precautions and central venous catheter dressing on the skin colonization around the insertion site.

AIM: The purpose of this prospective, randomized, controlled study was the comparison of maximal sterile barrier (consisting of mask, cap, sterile gloves, gown, large drape) vs control precautions (mask, cap, sterile gloves, small drape) and of transparent polyurethan film vs gauze dressing for use on central venous (CVC) nontunneled catheters, inserted via the jugular vein. Skin colonization at the insertion site (defined by quantitative skin cultures performed at the time of insertion and in days 2 and 5) was used as a primary endpoint. Catheter tip colonization was also assessed through qualitative culture and CVC related sepsis was defined by the isolation of the same organism from the catheter tip and the blood, with clinical sepsis of no other apparent source. METHODS: Eighty-two consecutive patients were enrolled, admitted to a mixed medical-surgical ICU, aged 72+/-12 years, 58% male, SAPS II 42+/-13. One-hundred and seven CVCs were studied (presenting 750 catheter in situ days); CVCs were in place for a mean period of 6.9+/-4.7 days and 5 episodes of central catheter-related bloodstream infection were detected (6.6 per 1000 catheter days). RESULTS: A multiple logistic regression detected an increased risk of skin colonization in male gender (OR=2.5) and control precautions (OR=3.4) and no difference with regard to age, dressing and diagnostic group. CONCLUSIONS: Maximal sterile barrier proved to be an effective and recommended practice. However surveillance skin cultures revealed the common and changing nature of colonization of skin at the insertion site.

CD38 as a target of IB4 mAb carrying saporin-S6: design of an immunotoxin for ex vivo depletion of hematological CD38+ neoplasia.

An anti-CD38 mAb (IB4) coupled to saporin-S6, a type 1 ribosome-inactivating protein (RIP), was designed for ex vivo or loco-regional therapeutical applications in myeloma and lymphoma. The ability of this immunotoxin to eliminate CD38+ cells was studied in vitro on selected CD38+ human cell lines (Raji, HBL6, L540 and CEM) and on CD38+ neoplastic cells from a Non Hodgkin Lymphoma (NHL) patient. HBL6, Raji and L540 cells resulted very sensitive to the IB4/saporin-S6 conjugate, concentrations as low as 100 pM of the immunotoxin completely inhibited protein synthesis. CD38+ neoplastic cells from the NHL patient were completely eliminated after treatment with immunotoxin at 10 nM concentration. CFU-c rescue by bone marrow precursors was maintained after exposure to the immunotoxin. These results indicate that IB4/saporin-S6 is endowed with strong and specific cytotoxic effects on selected CD38+ tumor cells lineages. Consequently, it is reasonable to propose a clinical use of the IB4/saporin-S6 for ex vivo purging of unwanted cells (e.g. depletion of contaminating neoplastic cells in aphereses obtained from G-CSF-treated patients) or for loco-regional therapies of CD38+ tumors.