Pre-filled normal saline syringes to reduce totally implantable venous access device-associated bloodstream infection: a single institution pilot study.

Flushing totally implantable venous access devices (TIVADs) with manually filled saline syringes may increase contamination and catheter-related bloodstream infection (CRBSI). We used a retrospective cohort study to assess the impact of changing from manually filled syringes to manufactured pre-filled syringes on the frequency of CRBSI in 718 TIVADs. Manually filled syringes were used in 269 patients and pre-filled syringes in 449. The CRBSI rate was 2.7% in the pre-filled syringe group and 6.3% in the manually filled syringe group (P = 0.016). Sex, tumour type and stage, access site and access body side were not independent risk factors for CRBSI.

D(-)lentiginosine-induced apoptosis involves the intrinsic pathway and is p53-independent.

We have recently found that D(-)lentiginosine, a synthetic iminosugar exerting glucosidase inhibitory activity, but not its natural enantiomer lentiginosine, is endowed with an unexpected, pro-apoptotic activity. Here, we investigated mechanisms involved in apoptosis induced by D(-)lentiginosine in MOLT-3, HT-29 and SH-SY5Y tumour cell lines. The results showed that D(-)lentiginosine increased caspase 9 expression at 18 h in all the cell lines from 1.5-3.1 folds. Cytochrome c in the cytoplasm was found to be increased from 2.3-2.6 folds in treated cells with respect to control cells. These effects were accompanied by a remarkable collapse of the mitochondrial membrane potential and by the downregulation of anti-apoptotic genes, as well as the upregulation of pro-apoptotic genes of the Bcl-2 family. U937Bcl-2 transfectants, highly expressing Bcl-2, were reluctant to undergo apoptosis even following treatment with 500 µM D(-)lentiginosine, whereas apoptosis by D(-)lentiginosine was induced also in U937 cells, naturally deficient in P53. Thus, our study establishes that the enantiomer of a natural iminosugar is endowed with a possible anti-tumorigenic effect that might be ascribed not only to their capacity to inhibit glycosidases but also to other unknown mechanisms. These data encourage further investigation on similar compounds to make them an interesting platform for the generation of new anticancer drugs.

A comparison of two agar gel immunodiffusion methods and a complement fixation test for serologic diagnosis of Brucella ovis infection in experimentally infected rams / Comparação entre dois métodos de imunodifusão em gel de Agar e um método de fixação de complemento para o diagnóstico sorológico da infecção por Brucella ovis em carneiros experimentalmente infectados

A infecção por Brucella ovis é considerada uma das principais causas de epididimite e infertilidade em carneiros, resultando em falhas reprodutivas e perdas econômicas significativas em rebanhos ovinos ao redor do mundo. O estudo teve o objetivo de avaliar três testes sorológicos disponíveis para o diagnóstico da brucelose ovina por B. ovis, utilizando 181 soros ovinos. Amostras de soro provenientes de carneiros experimentalmente infectados foram coletadas ao longo de 192 dias pós-infecção (n=117) e durante o período pré-infecção (n=9). Adicionalmente, amostras de soro foram obtidas de ovinos provenientes de um rebanho livre para B. ovis (n=55). As técnicas de imunodifusão em gel de agar (IDGA), utilizando dois antígenos disponíveis comercialmente, e de fixação de complemento foram comparadas (FC). Foram obtidos resultados de sensibilidade especificidade semelhantes para ambos os métodos de IDGA e ainda, a técnica de IDGA foi mais eficiente do que a da FC para o diagnóstico sorológico da infecção por B. ovis.

The use of biomarkers for risk assessment: Reporting from the INTARESE/ENVIRISK Workshop in Prague.

This publication is a report on the workshop "The use of biomarkers for risk assessment" which took place in November 2007 in Prague, the Czech Republic. The main aim of the workshop was to bring together a broad international audience with a particular interest in the development and application of human biomonitoring (HBM) and biomarkers for environmental health research, and to provide a state-of-the art overview of the potential values and pitfalls of biomarkers in risk assessment. Throughout the presentations and the subsequent discussions, it was shown that human biomonitoring is a highly plastic and versatile tool for the unraveling of the link between contaminants in the environment and potentially associated health effects in the general population. Although it offers a means to integrate exposure through different environmental compartments, to integrate exposure over time, to include individual risk factors and genetic susceptibility, exposure biomarkers would greatly benefit from standardized, accurate and sensitive detection methods and toxicokinetic data. Effect biomarkers on the other hand need to be put into their relevant public health perspective, and well validated, mechanistically sound dose-response relationships are essential. New developments, such as in vitro assays and "-omics", may drastically improve our knowledge on the causal mechanisms behind environmental health associations and will allow for a more informed linkage of toxicological and epidemiological reality.

Inhibition of NF-κB activation sensitizes U937 cells to 3'-azido-3'-deoxythymidine induced apoptosis.

In this study, we investigated molecular mechanisms underlying low susceptibility to apoptosis induced by the nucleoside analog azidothymidine (AZT) and the role of nuclear factor-κB (NF-κB) activation in these phenomena. A preliminary screening in different cell lines indicated U937 monocytic cell line as suitable to this purpose. Treatment of U937 cells even with suprapharmacological concentrations of AZT induced only moderate levels of apoptosis. Surprisingly, SuperArray analysis showed that AZT induced the transcriptional activity of both pro- and anti-apoptotic genes. Interestingly, moreover, several genes upregulated by AZT were NF-κB related. In fact, AZT, after an initial inhibition of NF-κB activation with respect to control, induced a transient, but consistent, increase in NF-κB-binding activity. Inhibition of NF-κB activation in U937 cells, stably transfected with a dominant-negative IκBα or by pharmacological treatment, sensitized them to apoptosis induced by AZT and impaired the upregulation of anti-apoptotic genes in response to AZT treatment, with respect to control cells. These results indicate that NF-κB activation by AZT has a role in protecting target cells from apoptotic cell death, improving our understanding of the toxicology and the therapeutic usage of this drug.

New technologies: robotic-assisted laparoscopic dismembered pyeloplasty in adolescents. The first Italian experience.

AIM: The literature about pediatric robotic-assisted laparoscopic dismembered pyeloplasty (RALDP) is poor and limited to few series. This article reports the initial pediatric experience comparing it with the major series. METHODS: Between January 2006 and January 2007 at Umberto Parini Hospital in Aosta three patients were treated for left RALDP by a single senior surgeon. RESULTS: Mean age of the patients was 16.1 years (range 14.9-17.0). Mean body mass index was 21.6 kg/m2 (range 18.7-26.9). All patients were treated for left RALDP. Mean operative time (OT) was 160 minutes (range 120-185). Blood loss was null in all procedures and no interventions were converted to open. Mean postoperative hospitalization was 6.3 days (range 5-8). No intra- or postoperative complications occurred. CONCLUSIONS: This short series demonstrates that RALDP is feasible in adolescents as well and in a peripheral Centre high skilled in adult robotic urology. The OT is excellent in comparison with other series. A preliminary experience in adult robotic surgery and an initial collaboration with urologists for adults are strongly recommended.

Dynamics of the ion cyclotron resonance effect on amino acids adsorbed at the interfaces.

In this study we show a reproduction of the Zhadin experiment, which consists of the transient increase of the electrolytic current flow across an aqueous solution of L-arginine and L-glutamic acid induced by a proper low frequency alternating magnetic field superimposed to a static magnetic field of higher strength. We have identified the mechanisms that were at the origin of the so-far poor reproducibility of the above effect: the state of polarization of the electrode turned out to be a key parameter. The electrochemical investigation of the system shows that the observed phenomenon involves the transitory activation of the anode due to ion cyclotron frequency effect, followed again by anode passivation due to the adsorption of amino acid and its oxidation products. The likely occurrence of similar ion cyclotron resonance (ICR) phenomena at biological membranes, the implications on ion circulation in living matter, and the consequent biological impact of environmental magnetic fields are eventually discussed.

Cefazolin concentrations in serum during cardiopulmonary bypass surgery.

The objective of the study was to investigate possible changes in cefazolin serum levels induced by cardiopulmonary bypass (CPB). Six cardiac male patients who underwent cardiac surgery requiring CPB took part in the study. Cefazolin 2 g was intravenously infused over 60 min before anesthesia and blood samples were taken at appropriate times after drug administration (0, 0.25, 0.5, 1, 4, 6, 8 h), 2 min before and 5 min after the beginning and 2 min before and 5 min after the end of CPB. Drug serum concentrations were determined by means of a microbiological method. Five minutes after the start of CPB, cefazolin serum levels decreased on average by 46.6% and remained steadily low until 5 min after the end of CPB. Then, they rose on average by 37.3% at 4 h and then declined slowly until the last sampling at 8 h. Cefazolin serum concentrations were low during CPB but remained in a potentially effective range for antimicrobial prophylaxis for this surgery.

Prognostic factors in stage T1 grade 3 bladder cancer survival: the role of G1-S modulators (p53, p21Waf1, p27kip1, Cyclin D1, and Cyclin D3) and proliferation index (ki67-MIB1).

OBJECTIVE: To determine the prognostic value of a subset of regulators of the transition from G1-to-S phase of cell cycle in stage T1 grade 3 bladder cancers. METHODS: Fifty-one such cases were investigated to determine the significance on patient's survival of p53, p21Waf1, p27Kip1, Cyclin D1, Cyclin D3, and ki67-MIB1 (proliferation index). The statistical analysis included Kaplan-Meier methodology with Log-rank test and Cox' proportional hazard analysis. RESULTS: Tumor size (p=0.0034), and the labeling index of ki67-MIB1 (p=0.0034), p53 (p=0.0332), p27kip1 (p=0.0059) and Cyclin D1 (p=0.0103) were associated to disease-free survival. Progression-free survival was related to tumor size (p<0.0001), ki67 (p=0.0163), p53 (p=0.0041), p27kip1 (p=0.0161), Cyclin D1 (p<0.0001) and Cyclin D3 (p<0.0001). Patient's overall survival was associated to Cyclin D3 (p<0.0001), p53 (p=0.0017), p21Waf1 (p=0.0142), Cyclin D1 (p<0.0001), ki67-MIB1 (p=0.0450), and tumor size (p=0.0296). Down-regulation of p27kip1 and Cyclin D3 over-expression (disease-free), over-expression of p53, Cyclin D1 and Cyclin D3 (progression-free), and over-expression of Cyclin D3 (overall survival) were independent predictors by Cox's multivariate analysis. Down-regulation of p27kip1 (p<0.001, R.R. 0.997, 95%C.I. 0.995-0.999), and over-expression of Cyclin D1 (p<0.001, R.R. 1.009, 95%C.I. 1.004-1.014) and Cyclin D3 (p=0.005, R.R. 1.013, 95%C.I. 1.004-1.022) were the main independent predictors. CONCLUSION: Down-regulation of p27kip1 and over-expression of Cyclin D1 and Cyclin D3 might be relevant predictors of survival in stage T1 grade 3 bladder cancers, thus selecting a group of patients at higher risk of malignant behavior.

Immunocytochemical study by two photon fluorescence microscopy of the distribution of GABA(A) receptor subunits in rat cerebellar granule cells in culture.

An immunocytochemical investigation of the expression of alpha(1), alpha(6), beta(2/3), gamma(2) and delta subunits was performed on rat cerebellum granule cells in culture by the two photon microscopy technique. The first four subunits appear to be expressed abundantly in these cells, whereas the delta one seems to be expressed at a lower level. Another major difference in the distribution of these subunits is that whereas alpha(6), beta(2/3) and gamma(2) appear only on plasma membranes alpha(1) and delta are present mainly in the cell bodies cytoplasm. Still another difference was found in that the presence of gamma(2) on neurites is "polarized", preferentially labelling neurites with the appearance of dendrites. The subunits alpha(6) and beta(2/3) appear to label all types of neurites, with beta(2/3) being by far the most heavily expressed subunit type. A final distinct characteristic is that alpha(6) and, even more, gamma(2) appear to accumulate in the cytoplasmic domains immediately below the cone of emergence of neurites. This suggests a conspicuous transport of such subunits from the site of synthesis in the cell body to the site of final expression in the neurites (dendrites and axon terminals).

[European multicenter cross-sectional study on exposure to low doses of benzene]. / Studio trasversale multicentrico europeo su esposizione a basse dosi di benzene.

A cross-sectional multicenter european study has been carried out to evacuate the relations between exposure to low level of benzene and biological markers of internal dose (t,t-MA, S-PMA) and early biological effect (DNA-SSB). The research has shown significantly increased levels (adjusted for smoking habits) of the urinary excretion of t,t-MA, S-PMA and DNA-SSB in petrochemical workers (mean benzene level = 5,694 micrograms/m3) but not in filling station attendants, traffic police officers, and bus drivers compared to referent workers. Dose-response relations were detected between benzene air levels, t,t-MA, S-PMA and DNA-SSB in petrochemical workers, with significantly increased levels of DNA-SSB detected for benzene exposure levels in the range 391-1,800 micrograms/m3 (0.12-0.58 ppm).

Histological changes following two-step flap gastrocystoplasty in rats.

INTRODUCTION: A gastric segment used to increase bladder capacity can undergo considerable changes over time, as can all intestinal segments implanted in the urinary tract and in contact with urine. This experimental study reports the differences between the histological alterations observed in the gastric patch transposed in the bladder both with its own pedicle and after deafferentation from the stomach. MATERIALS AND METHODS: A group of 30 young male Sprague-Dawley rats underwent gastrocystoplasty. Survivors were divided into 3 groups: gastrocystoplasty alone (8 rats); gastrocystoplasty with vascular deafferentation at 15 days (7 rats), and at 2 months (8 rats). 5 rats were used as controls. Urinary pH was evaluated during a 6-month follow-up. RESULTS: Histology showed that early devascularization hindered the fusion of the two mucosae in the junctional area but reduced papillary hyperplasia (p = 0.013) of the gastric mucosa. No changes were observed in urinary pH after patch devascularization. CONCLUSIONS: Vascular deafferentation creates a gastric flap on the bladder which, even if it does not prevent urinary acidification, reduces the frequency of histologically detected changes susceptible for transformation into neoplasms.

A historical cohort mortality study among shipyard workers in Genoa, Italy.

BACKGROUND: A historical cohort mortality study was conducted among 3984 shipyard workers assigned to ship repair, refitting, and construction in the harbor of Genoa, Italy, between 1960 and 1981. These workers were exposed to asbestos fibers, welding fumes and gases, silica dust, polycyclic aromatic hydrocarbons, and solvents. METHODS: Workers were classified in 20 different job-titles depending upon the type of activity. Standardized mortality ratios (SMRs) were computed using male residents of the Province of Genoa as the referent population. RESULTS AND CONCLUSIONS: For the whole cohort significantly increased SMRs were detected for all causes, all cancers, liver, larynx, lung, pleural and bladder cancers, respiratory tract diseases, and cirrhosis of the liver. The analysis by job-title showed increased SMRs not only for pleural cancer, but also for lung, laryngeal cancers and respiratory tract diseases in occupations entailing heavy asbestos exposure. Bladder and liver cancers and liver cirrhosis mortality also appeared to be related to occupational exposure.

Occupational exposure to carbon black and risk of bladder cancer.

Exposure to carbon black has been linked to risk of lung and bladder cancer. We therefore investigated the frequency of these cancers in a group of 2286 longshoremen who were exposed occupationally to carbon-black dust. We identified 208 cancers (standardised incidence ratio 96, 95% CI 83-109), 53 lung cancers (108, 81-141), and 32 bladder cancers (130, 89-184). Longshoremen exposed to high concentrations of carbon black (n=14) had a significantly increased frequency of bladder cancer (204, 112-343). We conclude that the increase in bladder cancer in longshoremen is probably related to high exposure to carbon black.

Secondary thyroid carcinoma after allogeneic bone marrow transplantation during childhood.

The aim of this study was to evaluate the incidence and risk factors related to secondary thyroid carcinoma (STC) in patients who have undergone allogeneic BMT during childhood. Data related to the primary hematological disorder and BMT procedure were obtained from the records of 113 patients (42 F; 71 M) who underwent BMT before the age of 18 (median 10.0 years; range 1.7-18.0) and survived more than 3 years after transplant with a median follow-up of 10.1 years (range 3.0-19.0). Sixteen received cranial radiation (CRT) during first-line treatment. Pre-transplant conditioning included TBI in 85 patients, TAI in two, while 26 children did not receive irradiation. The standardized incidence ratio of STC after BMT was significantly higher (P < 0.001) than that of the general population. STC was found in eight patients, 3.1 to 15.7 years after transplant. All received TBI and three also CRT. The Cox's regression analysis, although not statistically significant due to the small study population, showed an increased risk in those who had received a cumulative radiation dose higher than 10 Gy and in those who developed chronic GVHD. Careful follow-up of thyroid status including annual ultrasound examination is recommended for early detection of tumor.

Reparación perineal transvaginal del rectocele sintomático mediante perineorrafia protésica con malla de marlex. Valoraciones anatomoclínicas, fisiológicas y de tratamiento / Transvaginal perineal repair of symptomatic rectocele using a Marlex mesh prosthesis: anatomoclinical, physiological and treatment considerations/assessment

Introducción. El propósito de este estudio es valorar el tratamiento de los rectoceles sintomáticos, en un grupo seleccionado de pacientes, mediante una técnica diseñada personalmente, en función de su etiología (fallo de la fascia de Denonvilliers), y con la colocación de una malla de Marlex. Pacientes y métodos. Se seleccionaron exclusivamente 12 pacientes en las cuales existía una historia de estreñimiento grave y que, además del uso diario de laxantes, recurrían a la digitación como única solución para la evacuación rectal. Se realizó un abordaje quirúrgico perineal transvaginal, colocándose una malla de Marlex anclada sobre la fascia de Denonvilliers y posteriormente una colpectomía romboidal posterior de la pared redundante. Resultados. Todas las pacientes notaron una mejoría inmediata de los síntomas con una evacuación sin necesidad de digitación, a la vez que desapareció el prolapso vaginal posterior. La rectificación del rectocele fue perfecta y se normalizaron los parámetros anatómicos, fisiológicos y radiológicos. Conclusiones. La perineorrafia protésica transvaginal mejora de forma definitiva los síntomas del rectocele de gran tamaño, tratando a la vez los dos parámetros anatomoclínicos, de distensión rectal anterior y prolapso vaginal posterior (AU)

IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. International Programme on Chemical Safety.

The purpose of these guidelines is to provide concise guidance on the planning, performing and interpretation of studies to monitor groups or individuals exposed to genotoxic agents. Most human carcinogens are genotoxic but not all genotoxic agents have been shown to be carcinogenic in humans. Although the main interest in these studies is due to the association of genotoxicity with carcinogenicity, there is also an inherent interest in monitoring human genotoxicity independently of cancer as an endpoint. The most often studied genotoxicity endpoints have been selected for inclusion in this document and they are structural and numerical chromosomal aberrations assessed using cytogenetic methods (classical chromosomal aberration analysis (CA), fluorescence in situ hybridisation (FISH), micronuclei (MN)); DNA damage (adducts, strand breaks, crosslinking, alkali-labile sites) assessed using bio-chemical/electrophoretic assays or sister chromatid exchanges (SCE); protein adducts; and hypoxanthine-guanine phosphoribosyltransferase (HPRT) mutations. The document does not consider germ cells or gene mutation assays other than HPRT or markers of oxidative stress, which have been applied on a more limited scale.

A simple modified arthroscopic procedure for fixation of displaced tibial eminence fractures.

SUMMARY: Avulsion fractures of the tibial eminence have been well described in children and adults with an increased in incidence resulting from road traffic and athletic accidents. According to the literature, only surgical treatment is advocated because of the high incidence of the nonunion and instability following conservative treatment. Open reduction can cause some morbidity and, therefore, arthroscopic techniques have been developed. The limitations of the techniques are related to technical difficulty and unstable fixation. We report a simple and effective method of fixation with the following advantages: (1) use of metallic suture for stable fixation, (2) the fixation device is easily removed in the office, (3) there is no need of additional instruments, and (4) the minimal size of the fixation device avoids damage to the anterior cruciate ligament insertion. This technique has been used in a series of 10 consecutive patients treated for avulsion fractures of the tibial spine since 1991, resulting in a high rate of excellent and good results without any case of nonunion fracture or related complication.

[Computerized tomography of the meniscus with a stress device]. / Studio con Tomografia Computerizzata dei menischi con apparecchio distrattore.

PURPOSE: We investigated the usefulness of a mechanical stress device to increase widening of the articular rima in CT studies of the meniscus on forced varus and valgus. MATERIAL AND METHODS: September 1997 to October 1998, we examined 284 patients with symptoms and clinical signs of meniscal injury. CT was performed during forced varus and valgus, depending on the site of the suspected damage, in 70 of 284 patients. We used an FOV of 18 cm, with a potential difference of 140 kVp and power of 170 mA. The reconstruction matrix was 512 x 512 and acquisition time was 3 s. A set of 8-10 partially overlapping scans were acquired craniocaudally, with slice thickness of 1.5 mm and gap of 1 mm. The mechanical strainer was locked in the correct position and a second set of 4-5 images acquired at the meniscus. Then the patients were submitted to arthroscopy to check the radiological findings. RESULTS: CT performed in forced varus and valgus had 96.8% specificity, 97.3% sensitivity and 97.1% diagnostic accuracy. Sensitivity was 100%, specificity 96% and diagnostic accuracy 98% in the medial meniscus, while we had 88.9%, 100% and 94.7% respectively in the external meniscus. CONCLUSIONS: CT with a mechanical stress device was extremely useful in defining the meniscal loose edge. It also showed the exact shape and complexity of meniscal injury, even in the cases with narrow articular rima or those where conventional CT had performed poorly.