Fidaxomicin versus oral vancomycin for severe Clostridium difficile infection: a retrospective cohort study.

OBJECTIVES: This study was conducted to compare clinical outcomes of fidaxomicin versus oral vancomycin in the management of severe Clostridium difficile infection (CDI). METHODS: The investigation was a retrospective, multicentre, propensity score-matched analysis using a national clinical administrative database. Veterans treated for severe CDI from any Veterans Affairs Medical Center between 1 June 2011 and 30 June 2017 were included if they received fidaxomicin or an oral vancomycin regimen for treatment. The two groups were matched by the nearest-neighbour method from a propensity score derived from independent variables associated with the selection of a fidaxomicin course. RESULTS: Propensity score matching resulted in two well-matched cohorts consisting of 213 fidaxomicin and 639 oral vancomycin courses. No statistically-significant difference was found for the primary outcome of combined clinical failure or recurrence (68/213 (31.9%) versus 163/639 (25.5%), respectively, p 0.071). Additionally, no statistically significant differences were found for the secondary outcomes of 30-day (23/213 (10.8%) versus 75/639 (11.7%), respectively, p 0.71), 90-day (48/213 (22.5%) versus 140/639 (21.9%), respectively, p 0.85), and 180-day mortality (62/213 (29.1%) versus 186/639 (29.1%), respectively, p 1.0) between the two treatment groups. CONCLUSIONS: Courses of fidaxomicin or oral vancomycin for severe CDI resulted in similar treatment outcomes. Study findings are consistent with current treatment guideline recommendations for the use of either agent in the management of severe CDI.

A systematic comparison of sugar content in low-fat vs regular versions of food.

Obesity remains a significant public health concern. One of the primary messages from providers and health-care organizations is to eat healthier foods with lower fat. Many in the lay press, however, have suggested that lower fat versions of foods contain more sugar. To our knowledge, a systematic comparison of the sugar content in food with lower fat alternatives has not been performed. In this study, we compared fat free, low fat and regular versions of the same foods using data collected from the USDA National Nutrient Database. We found that the amount of sugar is higher in the low fat (that is, reduced calorie, light, low fat) and non-fat than 'regular' versions of tested items (Friedman P=0.00001, Wilcoxon P=0.0002 for low fat vs regular food and P=0.0003 for non-fat vs regular food). Our data support the general belief that food that is lower in fat may contain more sugar.

Spark erosion: a high production rate method for producing Bi(0.5)Sb(1.5)Te3 nanoparticles with enhanced thermoelectric performance.

We report a new 'spark erosion' technique for producing high-quality thermoelectric nanoparticles at a remarkably high rate and with enhanced thermoelectric properties. The technique was utilized to synthesize p-type Bi(0.5)Sb(1.5)Te(3) nanoparticles with a production rate as high as 135 g h(-1), using a relatively small laboratory apparatus and low energy consumption. The compacted nanocomposite samples made from these nanoparticles exhibit a well-defined, 20-50 nm size nanograin microstructure, and show an enhanced figure of merit, ZT, of 1.36 at 360 K. Such a technique is essential for providing inexpensive, oxidation-free nanoparticles which are required for the fabrication of high performance thermoelectric devices for power generation from waste heat, and for refrigeration.

Prominent electrochromism through vacancy-order melting in a complex oxide.

Electrochromes are materials that have the ability to reversibly change from one colour state to another with the application of an electric field. Electrochromic colouration efficiency is typically large in organic materials that are not very stable chemically. Here we show that inorganic Bi(0.9)Ca(0.1)FeO(3-0.05) thin films exhibit a prominent electrochromic effect arising from an intrinsic mechanism due to the melting of oxygen-vacancy ordering and the associated redistribution of carriers. We use a combination of optical characterization techniques in conjunction with high-resolution transmission electron microscopy and first-principles theory. The absorption change and colouration efficiency at the band edge (blue-cyan region) are 4.8×10(6) m(-1) and 190 cm(2) C(-1), respectively, which are the highest reported values for inorganic electrochromes, even exceeding values of some organic materials.

Renal transplantation from living related donors: a single center experience in Viet Nam.

INTRODUCTION: End-stage renal disease is a major public health problem in Viet Nam. A cooperative project between the University of Liège, Belgium, and the University of Medicine Pham Ngoc Thach, Ho Chi Minh City, Viet Nam, has permitted the establishment of an autonomous program of renal transplantation from living-related donors at the Peoples' Hospital No 115. The aim of this paper was to report the primary results of the project and to draw conclusions for the future. PATIENTS AND METHODS: From January 2004 to July 2008, we performed 33 living-related renal transplantations. Mean ages of donors and recipients were 31.8 ± 9.5 and 41.6 ± 13.5 years, respectively. Laparoscopic nephrectomy was performed in 6 donors. The immunosuppressive regimen consisted of three drugs associated with induction therapy using anti-interleukin-2 receptor monoclonal antibody. RESULTS: The 33 donors are in good health at follow-up. Four developed major intra- or postoperative hemorrhage necessitating transfusion, with a surgical re-exploration in 1 donor. Wound infection occurred in 2 donors. Posttransplant recipient and graft survivals at 1 versus 3 years were 82% and 73% versus 82% and 65%, respectively. Eight recipients presented 13 biopsy-proven acute rejection episodes that were reversible in 7, but 1 patient lost his graft due to an irreversible rejection. Two recipients developed cancer. CONCLUSIONS: These initial results have encouraged us to continue the program of renal transplantation from living-related donors. However, they also pointed out the need to develop other donor sources.

A literature review of different pressure ulcer models from 1942-2005 and the development of an ideal animal model.

The literature from 1942-2005 was reviewed in order to determine an inexpensive animal model which can closely mimic pressure ulcers seen in humans of varying ages, without the need for surgical procedures. Two animal models for producing pressure ulcers were found to be inexpensive: pigs to mimic pressure ulcers in young humans due to their fixed skin, and rats to mimic pressure ulcers in the elderly due to their loose skin. The methods which were found to be inexpensive, reproducible, non-invasive and easy to carry out without the need of a surgeon or specialist were the use of magnets for rat models and the use of a cast placed over a bony prominence for pig models.

Moexipril and left ventricular hypertrophy.

Angiotensin-converting enzyme (ACE) inhibitors today are the standard therapy of patients with myocardial infarction and heart failure due to their proven beneficial effects in left ventricular remodeling and left ventricular function. ACE inhibitors have also been demonstrated to lead to regression of left ventricular hypertrophy (LVH). It is believed that the mechanism of action of LVH regression with ACE inhibitors arises from more than simple blood pressure reduction. LVH is an important risk factor for cardiovascular disease morbidity and mortality independent of blood pressure. Moexipril hydrochloride is a long-acting, non-sulfhydryl ACE inhibitor that can be taken once daily for the treatment of hypertension. Moexipril has now also been demonstrated to have beneficial effects on LVH and can lead to LVH regression.

Caspase-3 inhibition partially protects oxidant production in apoptotic human neutrophils.

UNLABELLED: Apoptotic PMN lose functional activity, which emphasizes the tissue injury limiting potential of PMN apoptosis. Caspase-3 activation is the first step in the execution phase of apoptosis. We hypothesized that PMN functional activity, as evidenced by oxidant production, can be restored in apoptotic PMN by inhibition of caspase-3. METHODS: To accelerate PMN apoptosis, PMN were UV-irradiated for 15 min as previously described. PMN were pretreated with the caspase-3 inhibitor DEVD-fmk (100 microM) for 30 min prior to UV. PMN apoptosis was quantitated by flow cytometry with CD16 staining. Oxidant production in response to 10 microM PMA was quantitated fluorometrically using the method of Hyslop and Sklar. Caspase-3 activity was quantitated fluorometrically using a commercially available assay. RESULTS: UV-treated PMN demonstrated a 3-fold increase in caspase-3 activity. This was associated with a significant increase in apoptotic PMN and a 10-fold decrease in oxidant production compared to control PMN. DEVD-fmk blocked increases in caspase-3 activity and significantly reduced PMN apoptosis. Oxidant production was increased 5-fold compared to UV-treated PMN but was still significantly less than control PMN. CONCLUSIONS: In UV-accelerated PMN apoptosis, inhibition of caspase-3 activity partially protects oxidant production in apoptotic PMN. This suggests that signaling events in the initiation phase of PMN apoptosis, which are proximal to caspase-3 activation, may in part be responsible for loss of oxidant production in apoptotic PMN independent of caspase-3 activity.

Chelerythrine chloride induces rapid polymorphonuclear leukocyte apoptosis through activation of caspase-3.

Polymorphonuclear leukocytes (PMN) play a primary role in the initiation and propagation of inflammatory responses. PMN apoptosis is a major mechanism associated with the resolution of inflammatory reactions. Understanding mechanisms associated with PMN apoptosis will be of critical value in the development of novel pharmacological treatment strategies for local and/or systemic inflammatory disorders. The present study demonstrates that chelerythrine chloride induces human PMN to undergo rapid and synchronous progression into the apoptotic process via a PKC-independent mechanism. The appearance of the morphological features of apoptosis in chelerythrine-treated PMN is preceded by a significant upregulation in caspase-3 activity. GM-CSF (a cytokine that protects PMN in several models of PMN apoptosis) does not protect PMN from chelerythrine chloride-induced apoptosis.

Granulocyte-macrophage colony-stimulating factor rescues human polymorphonuclear leukocytes from ultraviolet irradiation-accelerated apoptosis.

INTRODUCTION: Bacterial lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF) delay PMN apoptosis during in vitro culture. The present study was undertaken to determine if LPS and GM-CSF can rescue UV-irradiated PMN from undergoing apoptosis and to determine the role of extracellular signal-regulated kinase (ERK) in this process. MATERIALS AND METHODS: PMN were preincubated with LPS (20 ng/ml) and GM-CSF (100 units/ml) for 60 min before being UV-irradiated for 15 min. Additional PMN were UV-irradiated for 15 min and then treated with LPS and GM-CSF. To determine the role of ERK in protection or rescue of PMN from apoptosis, PMN were preincubated with PD098059 for 30 min. Morphologic features of apoptosis were determined 4 h after UV irradiation. DNA laddering was confirmed by agarose gel electrophoresis. RESULTS: LPS and GM-CSF pretreatment significantly protected PMN from UV-accelerated apoptosis, although GM-CSF was more effective than LPS. Only GM-CSF rescued PMN that had already been exposed to UV irradiation from undergoing apoptosis. Time response experiments demonstrated that GM-CSF rescued a significant percentage of PMN when added up to 90 min after UV irradiation. Inhibition of ERK with PD098059 abrogated the protective effect of LPS and GM-CSF and blocked rescue of PMN from apoptosis by GM-CSF. CONCLUSIONS: LPS and GM-CSF protect PMN, whereas only GM-CSF can rescue PMN from UV-accelerated apoptosis. The ERK-signaling pathway plays an important role in the protection and/or rescue of PMN from UV-accelerated apoptosis, but appears to be a proximal event in this process. This study provides further insight into factors that regulate PMN apoptosis and provides a novel approach for investigating signal transduction pathways involved in PMN apoptosis.

Lipopolysaccharide protects polymorphonuclear leukocytes from apoptosis via tyrosine phosphorylation-dependent signal transduction pathways.

BACKGROUND: The present study was undertaken to determine if tyrosine phosphorylation signal transduction pathways, which are known to be activated in polymorphonuclear leukocytes (PMN) by lipopolysaccharide (LPS), play a role in priming of PMN oxidative burst and protection of PMN from apoptosis by LPS, and to determine if an interface between these two signaling pathways exists. METHODS: PMN were combined with or without 10-fold serial dilutions (0.1 ng-1 microgram/ml) of LPS and incubated at 37 degrees C/5% CO2. After 24 h PMN apoptosis was assessed using fluorescence microscopy and DNA agarose gel electrophoresis. Additional PMN were pretreated with the tyrosine kinase inhibitors genistein and herbamycin A before addition of LPS. Tyrosine phosphorylation was detected by immunoblotting. Oxidant production was quantitated by following the oxidation of a chromophore to its fluorescent product. RESULTS: LPS delayed the onset of apoptosis and prolonged the survival of PMN in a dose-dependent fashion. Both tyrosine kinase inhibitors blocked the protective effect of LPS on PMN apoptosis; however, only genistein blocked the priming effect of LPS on PMN oxidative burst. CONCLUSIONS: Tyrosine phosphorylation signal transduction pathways are central to protection of PMN from apoptosis by LPS. Although tyrosine phosphorylation pathways also play a role in priming of the oxidative burst in PMN, our data suggest that there is not an interface between these important signaling pathways.

Autocrine/paracrine modulation of polymorphonuclear leukocyte survival after exposure to Candida albicans.

Polymorphonuclear leukocytes (PMN) play a central role in the host response to injury and infection. These terminally differentiated phagocytes have a limited life span, after which they undergo spontaneous apoptosis. PMN life span can be significantly prolonged by several naturally occurring cytokines, and PMN are now known to be capable of cytokine production in response to various antigenic stimuli. These facts suggest the possibility that PMN possess an autocrine/paracrine mechanism for the control of their own survival. The present study was undertaken to test this hypothesis. Supernatants from PMN that had been incubated with Candida albicans for 18 h significantly decreased the number of fresh PMN demonstrating features of apoptosis and increased the percentage of viable PMN during in vitro culture. This was demonstrated by monitoring morphologic features of apoptosis with fluorescence microscopy and DNA endonuclease activity with agarose gel electrophoresis. Significant levels of tumor necrosis factor (TNF) were detectable in the supernatants of PMN that had been stimulated with C. albicans, as determined using a TNF-sensitive cell line. Neutralization of TNF biologic activity with a specific monoclonal antibody partially abrogated the supernatant-mediated prolongation of PMN survival. The present study demonstrates that PMN possess a mechanism for the modulation of their own survival, which in part may be through the production of TNF.

Ultraviolet irradiation accelerates apoptosis in human polymorphonuclear leukocytes: protection by LPS and GM-CSF.

Polymorphonuclear leukocytes (PMN) play a central role in host response to injury and infection. Understanding factors that regulate PMN survival may therefore have a major influence on the development of novel treatment strategies for controlling life-threatening infections, as well as local and systemic inflammatory responses. Unfortunately, the presently utilized in vitro culture model of PMN apoptosis makes the examination of early biochemical events surrounding PMN apoptosis very difficult. This study demonstrates that a short course of UV irradiation (15 min) can be used to induce rapid progression of PMN through the apoptotic process with 70-90% of PMN displaying features of apoptosis by 4 h after UV exposure. Bacterial lipopolysaccharide and granulocyte-macrophage colony-stimulating factor, which are known to prolong PMN survival during in vitro culture, also protected PMN from UV-accelerated apoptosis. The UV-accelerated model of PMN apoptosis provides another valuable tool for the investigation of early signaling pathways associated with inducing or delaying PMN apoptosis.

Flow cytometric analysis of kappa and lambda light chain expression in evaluation of specimens for B-cell neoplasia.

Analysis of light chain expression is one of the most important determinations in flow cytometric immunophenotyping of patient specimens. Numerous technical factors, such as antibody choice and cytophilic antibody artifact, impact a laboratory's ability to perform this test. There have been conflicting reports concerning the efficacy of polyclonal versus monoclonal antibodies, as well as methods of circumventing cytophilic antibodies, indicating that a consensus has not been reached on optimal methods for light chain determination. The authors have investigated methods for light chain analysis in 104 normal donors and 366 patient specimens, comparing different anti-light chain antibodies as well as strategies for analysis of specimens with low numbers of monoclonal B cells, admixed polyclonal B cells, or cytophilic antibodies. The patient specimens were either part of the initial diagnostic evaluation of patients with suspected lymphoma, or were performed for staging or assessment of treatment of patients with known B-cell neoplasia. No monoclonality was detected in control specimens, and there was no significant difference in staining with monoclonal verses polyclonal anti-light chain antibodies. In addition, cytophilic antibody did not obscure results in normal controls. Monoclonality was detected in 106 patient specimens, with 89 showing gross involvement with a predominant monoclonal B-cell process. However, in 43% of the grossly monoclonal specimens, there was failure to detect monoclonality with at least one light chain antibody set, with 8% of these cases showing failure with two anti-light chain sets. This indicates the importance of antibody choice in light chain analysis. Cytophilic antibody artifact in monoclonal specimens was easily overcome by appropriate antibody combinations, obviating the need for cytophilic antibody-shedding by incubation at 37 degrees C in fetal calf serum. In 27 patient specimens with low numbers of B cells or admixed polyclonal B cells, a clonal search based on FSC and CD19 or CD20 expression was performed. In 17 of the 27 cases (63%), a small monoclonal population was detected among admixed polyclonal B cells. The authors conclude that multiple strategies are necessary in flow cytometric analysis for B-cell monoclonality.

The treatment of hydrocephalus in preterm infants with intraventricular haemorrhage.

The hospital charts and clinical course of forty-one patients requiring one or more ventricular drainage procedures for hydrocephalic complications of neonatal intraventricular haemorrhage were evaluated retrospectively. All drainage procedures were performed on patients with intraventricular haemorrhage with ventricular dilatation (Grade III [25 patients]) and intraventricular and intraparenchymal haemorrhage (Grade IV [16 patients]) who were medical management failures. Twenty-six ventricular reservoirs (Rickham or McComb reservoirs) were placed in neonates weighing less than 1500 grams, allowing for a safe but intermittent ventricular access. Eighteen of these reservoirs were subsequently converted to ventriculoperitoneal shunts. Thirty-two percent of the patients incurred a shunt and/or reservoir infection and 59% required a shunt revision during the first year of life. There was no mortality related to the neurosurgical interventions. These results compare favorably with the published literature. No grade IV patients achieved a normal functional level, while 10 grade III patients did. The incidence of severe developmental delay (44% versus 28%) and death (38% versus 12%) was greater in the grade IV than the grade III patients. The placement of ventricular reservoirs is acceptable as an alternative to the early placement of ventriculo-peritoneal shunts. This approach may reduce the incidence of shunt infection as well as noninfectious shunt complications.

Products of cells cultured from gliomas. V. Cytology and morphometry of two cell types cultured from glioma.

Explants of cells of a human glioma were evaluated with the nuclear fluorochrome 4',6-diamidino-2-phenylindole, by phase-contrast illumination, and by Giemsa staining correlated with double immunofluorescence for glial fibrillary acidic protein (GFAP) and fibronectin (FN). FN-positive (FN+) cells lacked GFAP detectable by immunofluorescence. Their mean nuclear-to-cytoplasmic ratio was large (0.192). Actual mean areas of nuclei (1,252 microns2) and cytoplasm (8,376 microns2) of FN+ cells compared with mean areas of fibroblasts suggested that the high nuclear-to-cytoplasmic ratio of FN+ cells was due to their microscopically evident reduced cytoplasmic spreading rather than to larger nuclei. Some FN+ cells showed marked variation in nuclear and nucleolar size and shape. Others had abnormal mitoses or hyperchromatic nuclei. GFAP-positive (GFAP+) cells lacked FN detectable by immunofluorescence. GFAP+ cells were smaller and less round than FN+ cells. Their usual location was growing on a layer of FN+ cells. The mean nuclear-to-cytoplasmic ratio (0.245) of GFAP+ cells was the highest in the study, surpassing the ratio of the continuous glioma line LM (0.176). Mean areas of nuclei (289 microns2) and of cytoplasm (1,350 microns2) of GFAP+ cells suggested that their high nuclear-to-cytoplasmic ratio was due to their microscopically evident reduced cytoplasmic spreading. Reduced spreading was associated with extension of long, thin cytoplasmic processes. The majority of GFAP+ cells showed marked cytoplasmic basophilia, nuclear hyperchromasia, and clumped chromatin. Features observed in both FN+ and GFAP+ cells from this high-grade astrocytoma are features associated with malignant transformation in more thoroughly studied tumor systems.