Relevance of multidrug-resistant Pseudomonas aeruginosa infections in cystic fibrosis.

Multidrug-resistant (MDR) Pseudomonas aeruginosa is an important issue for physicians who take care of patients with cystic fibrosis (CF). Here, we review the latest research on how P. aeruginosa infection causes lung function to decline and how several factors contribute to the emergence of antibiotic resistance in P. aeruginosa strains and influence the course of the infection course. However, many aspects of the practical management of patients with CF infected with MDR P. aeruginosa are still to be established. Less is known about the exact role of susceptibility testing in clinical strategies for dealing with resistant infections, and there is an urgent need to find a tool to assist in choosing the best therapeutic strategy for MDR P. aeruginosa infection. One current perception is that the selection of antibiotic therapy according to antibiogram results is an important component of the decision-making process, but other patient factors, such as previous infection history and antibiotic courses, also need to be evaluated. On the basis of the known issues and the best current data on respiratory infections caused by MDR P. aeruginosa, this review provides practical suggestions to optimize the diagnostic and therapeutic management of patients with CF who are infected with these pathogens.

Th2 cytokines impair innate immune responses to rhinovirus in respiratory epithelial cells.

BACKGROUND: Asthma and other Th2 inflammatory conditions have been associated with increased susceptibility to viral infections. The mechanisms by which Th2 cytokines can influence immune responses to infections are largely unknown. METHODS: We measured the effects of Th2 cytokines (IL-4 and IL-13) on bronchial epithelial cell innate immune antiviral responses by assessing interferon (IFN-ß and IFN-λ1) induction following rhinovirus (RV)-16 infection. We also investigated the modulatory effects of Th2 cytokines on Toll-like receptor 3 (TLR3), interferon-responsive factor 3 (IRF3) and nuclear factor (NF)-kB, that is key molecules and transcription factors involved in the rhinovirus-induced interferon production and inflammatory cascade. Pharmacological and redox modulation of these pathways was also assessed. RESULTS: Th2 cytokines impaired RV-16-induced interferon production, increased rhinovirus replication and impaired TLR3 expression in bronchial epithelial cells. These results were replicated in vivo: we found increased IL-4 mRNA levels in nasal epithelial cells from nasal brushing of atopic rhinitis patients and a parallel reduction in TLR3 expression and increased RV-16 replication compared to nonatopic subjects. Mechanistically, Th2 cytokines impaired RV-16-induced activation of IRF3, but had no effects on RV-16-induced NF-kB activation in bronchial epithelial cell cultures. N-acetylcysteine and phosphoinositide 3-kinase (PI3K) inhibitor restored the inhibitory effects of Th2 cytokines over RV-16-induced activation of IRF3. CONCLUSIONS: IL-4 and IL-13, through inhibition of TLR3 expression and signalling (IRF3), impair immune response to RV-16 infection. These data suggest that Th2 conditions increase susceptibility to infections and identify pharmacological approaches with potential to restore impaired immune response in these conditions.

A Health Technology Assessment: laparoscopy versus colpoceliotomy.

INTRODUCTION: The objective of this paper is the comparison between two different technologies used for the removal of a uterine myoma, a frequent benign tumor: the standard technology currently used, laparoscopy, and an innovative one, colpoceliotomy. It was considered relevant to evaluate the real and the potential effects of the two technologies implementation and, in addition, the consequences that the introduction or exclusion of the innovative technology would have for both the National Health System (NHS) and the entire community. METHODS: The comparison between these two different technologies, the standard and the innovative one, was conducted using a Health Technology Assessment (HTA). In particular, in order to analyse their differences, a multi-dimensional approach was considered: effectiveness, costs and budget impact analysis data were collected, applying different instruments, such as the Activity Based Costing methodology (ABC), the Cost-Effectiveness Analysis (CEA) and the Budget Impact Analysis (BIA). Organisational, equity and social impact were also evaluated. RESULTS: The results showed that the introduction of colpoceliotomy would provide significant economic savings to the Regional and National Health Service; in particular, a saving of € 453.27 for each surgical procedure. DISCUSSION: The introduction of the innovative technology, colpoceliotomy, could be considered a valuable tool; one offering many advantages related to less invasiveness and a shorter surgical procedure than the standard technology currently used (laparoscopy).

Fatigue in patients undergoing radiation therapy: an observational study.

AIM: Fatigue can be defined as an unpleasant feeling of tiredness, weakness and lack of energy. It is found in about 80% of the patients receiving radiation therapy and has a significant impact on quality of life. The aim of this paper was to assess the frequency, severity and changes of fatigue before, during and after administration of a nutraceutical (mixture of whey protein with an high biological value, with an high content in native cysteine, albumin and lactoferrin in patients undergoing treatment for breast and prostate cancer. METHODS: Thirty patients (20 breast and 10 prostate ones) were enrolled in our test and they received a questionnaire about Fatigue developed by the University of Texas, MD Anderson Cancer Center, 1999. The patients who achieved a score between 4 and 6 were administered the nutraceutical (Prother) at a dose of 20 g / day for the first 10 days of radiation treatment and then 10 g/day for the following 20 days without considering the terms of the radiation oncology treatment [corrected]. Each patient was reassessed using the same Fatigue test after 10 and 30 days from the start of the administration of nutraceutical. We enrolled 30 control patients who did not receive Prother. RESULTS: The results showed the effectiveness of Prother in all patients with moderate-to-mild fatigue. CONCLUSION: The administration of Prother has therefore been effective in terms of both improving the compliance of the radiation treatment and the quality of life.

Analysis of errors in histology by root cause analysis: a pilot study.

INTRODUCTION: The study objective is to evaluate critical points in the process of pre-analytical histology in an Anatomic Pathology laboratory. Errors are an integral part of human systems, including the complex system of Anatomic Pathology. Previous studies focused on errors committed in diagnosis and did not consider the issues related to the histology preparation of routine processes. METHODS: Root Cause Analysis was applied to the process of histology preparation in order to identify the root cause of each previously identified problem. The analysis started by defining an 'a priori' list of errors that could occur in the histology preparation processes. During a three-month period, a trained technician tracked the errors encountered during the process and reported them on a form. 'Fishbone' diagram and 'Five whys' methods were then applied RESULTS: 8,346 histological cases were reviewed, for which 19,774 samples were made and from which 29,956 histologies were prepared. 132 errors were identified. Errors were detected in each phase: accessioning (6.5%), gross dissecting (28%), processing (1.5%), embedding (4.5%), tissue cutting and slide mounting (23%), coloring, (1.5%), labeling and releasing (35%). DISCUSSION: Root cause analysis is effective and easy to use in clinical risk management. It is an important step for the identification and prevention of errors, that are frequently due to multiple causes. Developing operators' awareness of their central role in the risk management process is possible by targeted training. Furthermore, by highlighting the most relevant points of interest, it is possible to improve both the methodology and the procedural safety.

Efficacy of embryo transfer in lactating dairy cows during summer using fresh or vitrified embryos produced in vitro with sex-sorted semen.

The objective was to determine whether transfer of fresh or vitrified embryos produced in vitro with sex-sorted semen improves pregnancy and calving rates during summer in lactating dairy cows compared with artificial insemination (AI). Lactating dairy cows (n=722) were enrolled during summer months at 2 commercial dairies in Central Texas and randomly assigned to 1 of 3 treatments: AI with conventional semen (n=227), embryo transfer-vitrified (ET-V; n=279) or embryo transfer-fresh (ET-F; n=216). Embryos were produced in vitro using sex-sorted semen and with Block-Bonilla-Hansen-7 culture medium. For vitrification, grade 1 expanded blastocysts were harvested on d 7 after fertilization and vitrified using the open-pulled straw method. Fresh embryos were grade 1 blastocysts and expanded blastocysts harvested on d 7 after fertilization. Cows were submitted to the Ovsynch56 protocol: d -10 GnRH, d -3 PGF(2α), d -1 GnRH and d 0 timed AI; or Select Synch protocol: d -9 GnRH, d -2 PGF(2α), and AI following detected estrus (day of AI=d 0). On d 7, all cows were examined for presence of a corpus luteum (CL). A vitrified or fresh embryo was transferred to cows with CL in ET-V and ET-F groups. Cows were considered synchronized if progesterone was <1ng/mL on d 0 and a CL was present on d 7. At d 40±7 of gestation, the percentage of cows pregnant was greater for the ET-F compared with the ET-V and AI groups among all cows (42.1 vs. 29.3 and 18.3%, respectively) and synchronized cows (45.5 vs. 31.6 and 24.8%, respectively). Also, the percentage of cows pregnant was greater for the ET-V than the AI group among all cows and tended to be greater among synchronized cows. At d 97±7 of gestation, the percentage of cows pregnant among all cows was greater for ET-F and ET-V groups than for the AI group (36.4 and 25.7 vs. 17.0%, respectively) and the percentage for the ET-F group was greater than for the ET-V group. Among synchronized cows, the percentage of cows pregnant was significantly increased for the ET-F group than for ET-V and AI groups (39.4 vs. 27.8 and 23.1%, respectively) and no difference was found between ET-V and AI groups. No effect of treatment on embryo loss was observed. The percentage of cows with live births was significantly increased for the ET-F than for ET-V and AI groups among all cows (27.5 vs. 17.1 and 14.6%, respectively) and synchronized cows (29.9 vs. 18.5 and 20.0%, respectively). The percentage of cows giving birth to a live heifer was significantly increased for the ET-F and ET-V groups compared with the AI group among all cows (79.1 and 72.5 vs. 50.0%, respectively) and synchronized cows (79.1 and 72.5 vs. 50.0%, respectively). No difference existed between ET-F and ET-V groups for percent live heifer births but both were greater than for the AI group. The transfer of fresh embryos produced in vitro using sex-sorted semen to lactating dairy cows during summer can effectively increase the percentage of cows that establish pregnancy and also the percentage of cows that give birth to a live heifer compared with percentages from AI with conventional semen.

Effects of postbreeding gonadotropin treatments on conception rates of lactating dairy cows subjected to timed artificial insemination or embryo transfer in a tropical environment.

The objective of experiment 1 was to evaluate the effects of treatments with human chorionic gonadotropin (hCG) or GnRH 7 d after induced ovulation on reproductive performance of lactating dairy cows submitted to timed artificial insemination (TAI) or timed embryo transfer (TET). A total of 834 potential breedings were used from 661 lactating Holstein cows (37.3±0.3 kg of milk/d). Cows had ovulation synchronized and were assigned randomly to receive TAI on d 0 or TET on d 7. Within each group, cows were assigned randomly to receive on d 7 no additional treatment (control; nTAI=156; nTET=126), a 100 µg i.m. injection of GnRH (nTAI=155; nTET=124), or a 2,500 IU i.m. injection of hCG (nTAI=151; nTET=122). Postbreeding treatment affected the percentages of pregnant cows at TET on d 28 (control: 38.1%; GnRH: 52.4%; hCG: 45.1%) and on d 60 (control: 32.5%; GnRH: 41.1%; hCG: 38.5%), but postbreeding treatment did not affect percentages of pregnant cows at TAI on d 28 (control: 30.1%; GnRH: 32.2%; hCG: 32.4%) or on d 60 (control: 25.6%; GnRH: 27.1%; hCG: 29.8%). The objective of experiment 2 was to evaluate the effect of a treatment with GnRH 7 d after TET on reproductive performance of lactating dairy cows that received a previous GnRH treatment at TET. A total of 285 potential breedings were used from 257 lactating Holstein cows (35.1±0.8 kg of milk/d). Cows had ovulation synchronized and were assigned for TET on d 7. Immediately after TET, all cows were treated with a 100 µg i.m. injection of GnRH. On d 14, cows were assigned randomly to receive (G7-14; n=147) or not (G7; n=138) an additional injection of GnRH. Pregnancy diagnosis were performed on d 28 and 60. The additional treatment with GnRH on d 14 did not affect the percentages of pregnant cows on d 28 (G7: 48.5%; G7-14: 42.9%) or on d 60 (G7: 39.8%; G7-14: 37.4%). In conclusion, treatment with GnRH or hCG 7 d after induced ovulation increased conception rates in lactating dairy cows submitted to TET, but not in cows submitted to TAI. Moreover, treatment with GnRH 7 d after TET did not enhance reproductive performance of lactating dairy cows that received a previous GnRH treatment at TET.

Plasma adiponectin and leptin concentrations in professional rugby players.

Adipose tissue synthesizes and secretes a number of cytokine hormones, defined adipokines, which have emerged as critical regulators of several metabolic functions, including energy homeostasis, insulin action and lipid metabolism. The present study is aimed at assessing the relationship between plasma concentrations of leptin and adiponectin and body composition in a cohort of 38 male professional rugby players (age: 22-35 years). Anthropometric evaluation included body mass index (BMI, range: 23.4-35.1 kg/m2) and whole body bioelectric impedance to determine absolute fat-free mass (FFM), absolute fat mass (FAT), relative percentage of fat mass (FAT percent) and fat-free mass (FFM percent). FAT percent ranged from 15 to 34 percent, corresponding to a FAT of 11.5-38.7 kg, whereas FFM range was 62.1-83.5 kg. Plasma leptin range was 1.2-4.3 ng/mL and adiponectin range was 2.0-16.6 microg/mL. Plasma leptin and adiponectin concentrations and their ratio did not correlate with BMI, nor with FAT, FAT percent, FFM and FFM percent, even after correction for BMI. The findings of this study suggest that in professional rugby players some additional factors, like neuroendocrine adaptations, other than adipose mass play a relevant role in the determination of adipokine levels, which in this group appear to be rather independent of body composition.

Soluble transferrin receptor values in top level soccer players and skiers: comparison with sedentary people and pitfalls of laboratory methods.

AIM: Hematological assessment is crucial in athletes: the risk of sports' anemia should be monitored with hematological parameters and iron metabolism tests. The aim of this study was to evaluate soluble transferrin receptor (sTfR) efficacy, as it is highly sensitive and specific and usually utilized in sport medicine for monitoring iron metabolism. METHODS: sTfR was studied using two immunological methods (IDeA Orion, and Biokit) on a group of professional athletes, together with hematological and iron metabolism parameters. Values have been compared with those of sedentary people, before and during competitive season. Athletes were 76 professional male soccer players plus 20 males and 14 females of the alpine ski Italian National Teams. RESULTS: The sTfR values in athletes are similar to those found in sedentary people. Different results have been observed between the two different methods: a bias of 0.37 mg/L was found comparing them. A significant correlation between sTfR and iron, transferrin saturation, and reticulocytes was found in skiers; there was no correlation with hemoglobin, erythrocytes, ferritin. In soccer players significant differences have been retrieved among different teams' distribution of data. CONCLUSIONS: The principal limit for using sTfR in sports medicine, but also in the general population, is the lack of standardization among methods. The quantitative differences in athletes between the two methods are high, although the behavior of the parameter is similar from the quality point of view. The differences between measured concentrations could influence the thresholds used in antidoping context.

Relation between body mass index and serum aminotransferases concentrations in professional athletes.

AIM: Reference intervals commonly used for evaluating and interpreting laboratory values obtained in athletes are the same used in the general population. Aminotransferases (aspartate aminotransferase [AST], and alanine aminotransferase [ALT]) are commonly analyzed in serum for evaluating hepatic function. Some studies in the general population and in blood donors testified that ALT concentrations clearly correlated with weight and body mass. METHODS: We compared the aminotransferase concentrations at rest of 116 male professional athletes of 7 different sport disciplines with their body mass index (BMI). The blood drawing was performed before the start of training and of the competitive season. The athletes engaged in rugby, triathlon, soccer, sailing, cycling, basketball, alpine skiing. One hundred age-matched, apparently healthy, not physically active, males chosen for general check-up were recruited as a control group. RESULTS: The average concentrations of AST and ALT in the whole group of athletes were 24.4 U/L (standard deviation [SD]: 10.5) and 23.6 (SD: 6.5). The results in athletes were not statistically different from those of sedentary people. A positive correlation between BMI and ALT exists, whilst a very weak negative correlation between BMI and AST occurs. CONCLUSION: High concentrations of ALT should be evaluated considering BMI values whilst high values of AST should be evaluated considering the influence of physical exercise.

Persistent parvovirus B19-induced anemia in an HIV-infected patient under HAART. Case report and review of literature.

Recent reports document resolution of human parvovirus B19-related pure red blood cell aplasia (PB19-PRCA) in HIV-infected patients upon commencement of highly active antiretroviral therapy (HAART). This article describes a patient with PB19-PRCA who, despite fully suppressive HAART, required cyclic administration of intravenous human immunoglobulin over a period of 17 months before PB19 seroconversion and subsequent resolution of relapsing severe anemia. All reports in the English literature describing PB19-related hematologic abnormalities in the post-HAART era are also described herein.

FMECA methodology applied to two pathways in an orthopaedic hospital in Milan.

INTRODUCTION: Adverse events pose a challenge to medical management: they can produce mild or transient disabilities or lead to permanent disabilities or even death; preventable adverse events result from error or equipment failure. METHODS: IRCCS Istituto Ortopedico Galeazzi implemented a clinical risk management program in order to study the epidemiology of adverse events and to improve new pathways for preventing clinical errors: a risk management FMECA-FMEA pro-active analysis was applied either to an existing clinical support pathway or to a new process before its implementation. RESULTS: The application of FMEA-FMECA allowed the clinical risk unit of our hospital to undertake corrective actions in order to reduce the adverse events and errors on high-risk procedure used inside the hospitals.

Altered expression of the tetraspanin CD81 on B and T lymphocytes during HIV-1 infection.

CD81 is a member of the tetraspan superfamily and plays a role in immune responses and in hepatitis C virus (HCV) pathogenesis. We analysed CD81 cell surface and mRNA expression in different lymphocytic subpopulations in human immunodeficiency virus (HIV)-1, HCV and dually infected subjects. CD81 cell surface expression was evaluated with fluorescence activated cell sorter (FACS) analysis; mRNA quantification was performed with semiquantitative polymerase chain reaction (PCR). CD81 cell surface expression on CD4(+) T lymphocytes was significantly different by analysis of variance (anova) test (P < 0.001), with reduced expression in HIV-1(+) patients. In B lymphocytes, higher cell surface expression was present in HIV-1, in HCV and in dually infected subjects compared to healthy controls. CD81 expression on B lymphocytes showed a positive correlation with plasma HIV-RNA. CD81 mRNA levels in B lymphocytes were significantly higher in HIV-1(+) patients compared to healthy controls. The potential consequence of the down-regulation of CD81 in CD4(+) cells during HIV-1 infection in conjunction with diverted CD28, CD4 and CD3 expression is the disruption of T cell function. Increased CD81 expression on B lymphocytes might explain the higher prevalence of lymphoproliferative disorders in HIV-1 and HCV infection. Up-regulation of CD81 mRNA on CD4(+) T cells indicates that down-regulation of CD81 occurs at the post-transcriptional/translational level.

Cost-benefit evaluation of influenza vaccination in the elderly in the Italian region of Liguria.

Influenza causes considerable morbidity and mortality and the damage to public health can be considerable. The most effective measures available for the prevention of influenza is vaccination. In most industrialised countries the objective of vaccination is to limit the disease among individuals at risk, especially the elderly. During the winter of 2000/2001, General Practitioners (GPs) monitored 14,818 elderly individuals. The objective was to evaluate the weekly incidence of the disease. Furthermore, we carried out a prospective study on 512 elderly individuals, arranged according to vaccination (304 vaccinated and 208 non-vaccinated), with the main objective of assessing the costs of the disease and the efficacy of vaccination. Finally, in order to assess the percentage of vaccinated elderly individuals, we carried out a telephone survey on 500 subjects. Our clinical surveillance study enabled us to establish that morbidity was particularly low in elderly individuals.The results of the prospective study allowed us to estimate the cost-benefit ratio at 8.22, with a net saving of 110.20 Euros for each vaccinated subject. We were also able to establish that the vaccine coverage among elderly individuals was 63%. Our study, though carried out during a low epidemic year, confirms the economic advantage of vaccination in the elderly.

Low-dose lansoprazole and clarithromycin plus metronidazole vs. full-dose lansoprazole and clarithromycin plus amoxicillin for eradication of Helicobacter pylori infection.

AIM: To compare, in a randomized controlled trial, the efficacy and tolerability of two 1-week triple therapies for Helicobacter pylori eradication. METHODS: One hundred and thirty-four consecutive patients with non-ulcer dyspepsia and H. pylori infection were randomized to receive lansoprazole 30 mg once daily, clarithromycin 250 mg twice daily, and metronidazole 500 mg twice daily (LCM group), or lansoprazole 30 mg twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1000 mg twice daily (LCA group). H. pylori status was assessed by rapid urease test, histology and 13C-urea breath test before and after therapy. RESULTS: At 3 months, H. pylori eradication (intention- to-treat/per protocol analysis) was 92.4%/93.8% in the LCM group and 83.1%/85.7% in the LCA group (P=N.S.). Side-effects were more frequently reported in the LCA group (37.9%) than in the LCM group (19.7%) (P < 0.05). CONCLUSIONS: In this open, randomized controlled trial, eradication of H. pylori by low-dose lansoprazole and clarithromycin plus metronidazole was higher with significantly less side-effects than by full-dose lansoprazole and clarithromycin plus amoxicillin. This finding may be related to the stronger synergism of clarithromycin plus metronidazole, even at lower doses, than of clarithromycin plus amoxicillin. Considering the lower cost as well, LCM should be preferred to LCA in the eradication of H. pylori.

Effect of genotypic resistance on the virological response to highly active antiretroviral therapy in cerebrospinal fluid.

Paired plasma and cerebrospinal fluid (CSF) specimens drawn from 15 HIV-infected patients with neurological disease before and after a median 6-week duration of highly active antiretroviral therapy (HAART) were studied to assess the short-term virological response of CSF and whether this can be predicted on the basis of baseline resistance mutations. After treatment, the median plasma and CSF viral load (VL) decreased by, respectively, 2.08 log10 (p = 0.0001) and 0.91 log10 copies/ml (p = 0.007) in comparison with baseline. A plasma virological response was observed in all but one patient, whereas the posttreatment CSF VL increased, remained unchanged, or decreased at a substantial lower rate than in plasma of six "CSF non/slow responders" (40%). Direct sequencing of baseline specimens showed that none of these patients had reverse transcriptase (RT) or primary protease resistance mutations in the CSF alone, but two had RT mutations conferring high-level resistance to drugs included in the HAART regimen in both CSF and plasma. The other four patients had no RT or primary protease resistance mutations. There was no significant difference in the nucleotide diversity of the CSF and plasma RT sequences, baseline plasma or CSF VL, the CSF-to-plasma VL ratio, the number of CSF cells, the CD4+ cell counts, or the history of antiretroviral treatment between the CSF non-slow responders and the other patients. During this short-term follow-up and despite a plasma response, a significant proportion of HAART-treated patients with neurological symptoms showed a slow or absent CSF response. Most of these cases were not associated with the presence of resistant HIV strains in the CSF.

'Eloquent chaos' in the oral discourse of killing fields survivors: an exploration of atrocity and narrativization.

If "narrative" implies a form of discourse in which sequenced events are meaningfully connected, an "anti-narrative" is a chaotic discourse form "of time without sequence, telling without mediation, and speaking about oneself without being fully able to reflect on oneself" (Frank 1995: 98). This paper examines narratives and anti-narratives in the oral discourses of survivors of the Cambodian killing fields. Through an extended analysis of two cases, we demonstrate the internal logic and "eloquence" of anti-narratives--i.e., the ways in which anti-narrative patterns vividly express and reveal a survivor's complex and continuing experience of atrocity.