Towards REPO4 nanocrystal-doped optical fibers for distributed sensing applications.

Rayleigh scattering enhanced nanoparticle-doped optical fibers, for distributed sensing applications, is a new technology that offers unique advantages to optical fiber community. However, the existing fabrication technology, based on in situ grown alkaline earth nanoparticles, is restricted to few compositions and exhibit a great dependence on many experimental conditions. Moreover, there is still several uncertainties about the effect of drawing process on the nanoparticle characteristics and its influence on the scattering enhancement and the induced optical loss. In this work, we shed light on all these issues that prevent the progress in the field and demonstrate the suitability of doping optical fibers with YPO4 nanocrystals for developing tunable Rayleigh scattering enhanced nanoparticle-doped optical fibers. An exhaustive 3D microstructural study reveals that their features are closely linked to the fiber drawing process, which allow the size and shape engineering at the nanoscale. In particular, the YPO4 nanocrystals preserve their features to a large extent when the optical fibers are drawn below 1950 °C, which allows obtaining homogeneous nanocrystal features and optical performance. Fabricated fibers exhibit a tunable enhanced backscattering in the range of 15.3-54.3 dB, with respect to a SMF-28 fiber, and two-way optical losses in the range 0.3-160.7 dB/m, revealed by Optical Backscatter Reflectometry (OBR) measurements. This allows sensing lengths from 0.3 m up to more than 58 m. The present work suggests a bright future of YPO4 nanocrystals for distributed sensing field and open a new gate towards the incorporation of other rare-earth orthophosphate (REPO4) nanocrystals with pre-defined characteristics that will overcome the limitations of the current in situ grown alkaline earth-based technology.

The EEG correlates and dangerous behavioral consequences of drowsy driving after a single night of mild sleep deprivation.

OBJECTIVE: Here, we investigated the behavioral, cognitive, and electrophysiological impact of mild, acute sleep loss via simultaneously recorded behavioral and electrophysiological measures of vigilance during a "real-world", simulated driving task. METHODS: Participants (N = 34) visited the lab for two testing days where their brain activity and vigilance were simultaneously recorded during a driving simulator task. The driving task lasted approximately 70 mins and consisted of tailgating the lead car at high speed, which braked randomly, requiring participants to react quickly to avoid crashing. The night before testing, participants either slept from 12am-9am (Normally Rested), or 1am-6am (Sleep Restriction). RESULTS: After a single night of mild sleep restriction, sleepiness was increased, participants took longer to brake, missed more braking events, and crashed more often. Brain activity showed more intense alpha burst activity and significant changes in EEG spectral power frequencies related to arousal (e.g., delta, theta, alpha). Importantly, increases in amplitude and number of alpha bursts predicted delays in reaction time when braking. CONCLUSIONS: The findings of this study suggest that a single night of mild sleep loss has significant, negative consequences on driving performance and vigilance, and a clear impact on the physiology of the brain in ways that reflect reduced arousal. SIGNIFICANCE: Understanding neural and cognitive changes associated with sleep loss may lead to important advancements in identifying and preventing potentially dangerous sleep-related lapses in vigilance.

Active recovery shows favorable IGF-I and IGF binding protein responses following heavy resistance exercise compared to passive recovery.

IGF-I and IGFBPs have important physiological modulatory effects and this study sought to examine the influence of active vs. passive recovery following a heavy resistance exercise on IGF-I and IGF binding protein (IGFBP) recovery responses. It was hypothesized that increased IGF-I and decreased inhibitory IGFBPs during active recovery may be reflective of cascades promoting physiological recovery. 18 untrained men ((AR n = 7, PR n = 11), age: 26 ±â€¯4 years, height: 174 ±â€¯8 cm, body mass: 75 ±â€¯13 kg) performed either a protocol-specific 10 × 10 × 30% 1RM active (AR) or passive recovery (PR) session following a heavy resistance exercise session performed on a leg press device (10 × 10 1RM). Maximal isometric force production (MVC) and IGF- and IGFBPs were measured pre, post, 1-hr post, and next morning. A significantly greater relative response in IGF-I was observed in AR than in PR at post recovery and next morning (p < .01 and statistical trend, respectively) while absolute concentrations of IGFBP-1 at next morning were significantly higher in PR than AR (p < .05), and relative IGFBP-1 response from control to next morning in PR was significantly greater than in AR (p < .001). IGFBP-1 may be inhibitory to IGF-I biological action, thus the lower concentration of IGFBP-1 after AR may be considered favorable in terms of recovery due to its positive relationship with glucose metabolism and maintaining metabolic homeostasis. These results suggest that some of the benefits of an active recovery bout may be mediated by favorable IGF-I system responses (increased IGF-I and decreased IGFBP-1) in the hormonal milieu that may assist facilitating the cascade of physiological recovery processes following acute heavy resistance loading exercise.

Driving safety improves after individualized training: An RCT involving older drivers in an urban area.

Objective: This study aimed to reproduce the results of a previous investigation on the safety benefits of individualized training for older drivers. We modified our method to address validity and generalizability issues. Methods: Older drivers were randomly assigned to one of the 3 arms: (1) education alone, (2) education + on road training, and (3) education + on road + simulator training. Older drivers were recruited from a larger urban community. At the pre- and posttests (separated by 4 to 8 weeks) participants followed driving directions using a Global Positioning System (GPS) navigation system. Results: Our findings support the positive influence of individualized on-road training for urban-dwelling older drivers. Overall, driving safety improved among drivers who received on-road training over those who were only exposed to an education session, F(1, 40) = 11.66, P = .001 (26% reduction in total unsafe driving actions [UDAs]). Statistically significant improvements were observed on observation UDAs (e.g., scanning at intersections, etc.), compliance UDAs (e.g., incomplete stop), and procedural UDAs (e.g., position in lane). Conclusion: This study adds to the growing evidence base in support of individualized older driver training to optimize older drivers' safety and promote continued safe driving.

Food habits during treatment of childhood cancer: a critical review.

Several factors can affect the nutritional status of children undergoing cancer therapy. The present review aims to describe children's food intake during cancer treatments and to explore the contributing determinants. It also assesses the nutritional educational interventions developed for this clientele. Scientific literature from January 1995 to January 2018 was searched through PubMed and MEDLINE using keywords related to childhood cancer and nutritional intake. Quantitative and qualitative studies were reviewed: forty-seven articles were selected: thirty-eight related to food intake and parental practices and nine related to nutritional interventions. Patients' intakes in energy, macronutrients and micronutrients were compared with those of healthy controls or with requirement standards. Generally, patients ate less energy and proteins than healthy children, but adhered similarly to national guidelines. There is a lack of consensus for standard nutrient requirement in this population and a need for more prospective evaluations. Qualitative studies provide an insight into the perceptions of children, parents and nurses on several determinants influencing eating behaviours, including the type of treatment and their side effects. Parental practices were found to be diverse. In general, savoury and salty foods were preferred to sweet foods. Finally, most interventional studies in childhood cancer have presented their protocol or assessed the feasibility of an intervention. Therefore, because of the variability of study designs and since only a few studies have presented results, their impact on the development of healthful eating habits remains unclear. A better understanding of children's nutritional intakes and eating behaviours during cancer treatment could guide future nutritional interventions.

Nutrition education and cooking workshops for families of children with cancer: a feasibility study.

BACKGROUND: Changes in food intake are common in children with cancer and are often caused by nausea and perturbations in sense of taste. The VIE (Valorization, Implication, Education) study proposes family-based nutrition and cooking education workshops during childhood cancer treatments. Process evaluation during implementation allows to assess if the intervention was delivered as planned and to determine its barriers and facilitators. The study objective was to describe the implementation process of a nutrition education and cooking workshop program for families of children actively treated for cancer in a non-randomized non-controlled feasibility study. METHODS: Six open-to-all in-hospital workshops were offered on a weekly basis during a one-year implementation phase. We collected qualitative and quantitative data using field notes and activity reports completed by the registered dietician facilitator; surveys and questionnaires fulfilled by the workshop participants and by the families enrolled in the VIE study. Field notes were used to collect only qualitative data. Survey respondents (n = 26) were mostly mothers (n = 19, 73%). Children's mean age was 7.80 (± 4.99) years and the mean time since diagnosis was 7.98 (± 0.81) months. Qualitative data were codified using hybrid content analysis. The first deductive analysis was based on the Steckler & Linnan concepts. Subthemes were then identified inductively. Quantitative data were presented with descriptive statistics. RESULTS: Workshop attendance was low (17 participants over 1 year) and 71% of the planned workshops were cancelled due to lack of participants. The principal barriers to participation referred the child's medical condition, parental presence required at the child's bedside and challenges related to logistics and time management. The level of interest in the topics addressed was found high or very high for 92% of the participants. The themes that were perceived as the most useful by parents were related to the child's specific medical condition. CONCLUSIONS: Despite high interest, workshops delivered in a face-to-face format were poorly feasible in our sample population. This supports the need to develop educational programs in pediatric oncology using strategies and delivery formats that address the major barriers for participation encountered by families.

Active and passive recovery influence responses of luteinizing hormone and testosterone to a fatiguing strength loading.

The purpose of this study was to examine the acute hormonal and muscular responses to a strenuous strength loading [bilateral leg press (LP) 10 × 10 1RM] followed by loading-specific active (AR, n = 7, LP 10 × 10 × 30% 1RM) or passive (PR, n = 11, seated) recovery. The subjects were men age: 26 ± 4 years, height: 174 ± 8 cm, body mass: 75 ± 13 kg. After control measurements, experimental measurements were conducted at pre- and post-loading as well as post-recovery and next morning. A significantly higher absolute concentration (p < 0.05) of serum luteinizing hormone (LH) was observed in AR than PR at next morning while no differences were observed in serum testosterone (T), cortisol (C) or sex hormone binding globulin (SHBG). Significant differences in relative hormonal responses to the loading were observed at next morning with greater responses observed in AR than in PR in terms of LH, and T (p < 0.05). Maximal bilateral isometric force (MVC) and countermovement jump height (CMJ) decreased significantly (p < 0.001) from the control measurements in both AR and PR but returned to control levels by next morning. No between-group differences were observed in mean absolute or relative changes in MVC or CMJ. From a hormonal perspective, the present AR method appears to have had some favorable effects following the strenuous strength loading; however, acute decreases in muscular force production did not significantly differ between groups. These results provide insight into the development of training programs that may help to support the performance of individuals involved in strenuous tasks.

[Multicenter multidisciplinary training program for chronic low back pain: French experience of the Renodos back pain network (Réseau Nord-Pas-de-Calais du DOS)].

OBJECTIVES: To evaluate the short- and long-term effectiveness of the multidisciplinary training program (MTP). To show the benefits which the network organization brings to the treatment of chronic low back pain (CLPB). METHODS: The member centres of the Renodos back pain network included 748 subjects in the MTP. The centres used a common evaluation protocol including pain and quality of life visual analogue scales (VAS), fingertip-to-floor distance (FFD), muscle isometric endurance tests, Roland-Morris Disability Questionnaire (RDQ), the Dallas Pain Questionnaire (DPQ) and the Hospital Anxiety Depression (HAD) scale. Measurements were carried out before (T0) and immediately after (T1) the intervention, and at the 3-, 6-, 12-month (T3, T6, T12) follow-up visits. RESULTS: Statistically discernible improvement occurred for men and women on every outcome measure from before to after the MTP (T0-T1, p<0.0001). This improvement obtained at T1 was maintained for most of the outcome measures throughout the 12-month follow-up. However, the pain intensity and isometric muscle endurance times showed significant negative evolution. Significant differences between genders were found for the trunk flexibility measurement (FFD), the isometric endurance time of the quadratus lumborum muscle, the RDQ and the HAD depression. There was no time-gender interaction. CONCLUSION: The MTP was effective in reducing back pain intensity, functional disability, symptoms of anxiety and depression and in improving quality of life, flexibility and isometric muscle endurance time. It was possible to propose the MTP to both men and women. A network organization effectively contributes to the harmonization of evaluation methods and brings coherence to the treatment of CLBP patients.

Purely axial compression of fiber Bragg gratings embedded in a highly deformable polymer.

We demonstrate a tuning device for fiber Bragg gratings with a wavelength tuning range in excess of 65 nm. A purely axial tuning technique using a highly deformable polymer molded in a cylinder shape is used to embed a fiber Bragg grating and to achieve a wavelength tuning range from 1551.7 to 1485.5 nm. The tuning curve is highly linear with a tuning rate of 9.6 nm for every percent of applied strain. The insertion losses of the device, the variations of the full width at half maximum, and the stability of the Bragg wavelength over a working day have been studied and shown to be less than 0.02 dB, 0.14, and 0.2 nm, respectively.

Cognitive structure of executive deficits in patients with frontal lesions performing activities of daily living.

OBJECTIVE: Executive function in activities of daily living (ADL) were investigated in 10 patients with excised frontal lobe tumours. METHOD: The patients with frontal lesions were compared to 10 normal controls with a neuropsychological test battery, a script generation task and a realistic implementation of complex multi-task ADL (planning and preparing a meal). RESULTS: The patients manifested numerous basic executive deficits on the paper-pencil tests, were unimpaired on the script generation task despite an aberrant semantic structure and manifested marked anomalies in the meal preparation task. CONCLUSION: Frontal lobe deficits in lengthy complex multi-task ADL can be explained by impairment of several executive functions, generalized slowness of performance and paucity of behaviour.

Prenatal blockade of estradiol synthesis impairs respiratory and metabolic responses to hypoxia in newborn and adult rats.

We tested the hypothesis that estradiol modifies respiratory control in pregnant rats and participates in the development of respiratory chemoreflexes in fetuses. Pregnant rats (n = 12) received daily subcutaneous injections of vehicle (Veh, n = 6) or 4-androsten-4-ol-3,17-dione acetate (ATD; inhibitor of estradiol synthesis; n = 6; 5 mg/day in vehicle) from gestational day 16 (G16) to delivery. Baseline ventilation (whole body plethysmography) and metabolic rate [oxygen consumption (Vo(2))] were determined at G14 and G20, in pups [on postnatal day 3 (P3) and P20] and in adult rats (on P70) born to Veh- or ATD-treated mothers. Hypoxic chemoreflex was assessed in P3 rats by acute exposure to 60% O(2) and in P20 or P70 rats by moderate hypoxia (12% O(2), 30 min). ATD treatment reduced circulating estradiol in pregnant dams at G20 without producing changes in the circulating level of estradiol precursors (testosterone and androstenedione). ATD-treated dams showed impaired respiratory adjustment to late gestation. Pups born to ATD mothers had higher resting Vo(2) (+23% at P3, +21% at P20), respiratory frequency (+15% at P3, +12% at P20), and minute ventilation (+11% at P3, +18% at P20) than pups from Veh mothers. Respiratory decrease during acute hyperoxic exposure at P3 was -9.7% in Veh (P < 0.05 vs. room air) and only -2.6% (P = not significant) in ATD pups. In P20 ATD rats, hypoxic ventilatory response was attenuated compared with Veh. In P20 and P70 rats, the drop of Vo(2) in hypoxia (-31% in P70, P < 0.0001) was not observed in ATD rats. We conclude that estradiol secreted during late gestation is necessary for respiratory adjustment to pregnancy and is required for adequate development of respiratory and metabolic control in the offspring.

Script generation following frontal and parietal lesions.

The purpose of this investigation was to distinguish putative effects of parietal lobe lesions on script generation, in distinction from the better known and established effects of frontal lobe lesions. Nine patients, most with excised parietal lesions, were compared to nine age, gender and education matched normal participants. Eleven patients with excised tumors of the frontal lobe were compared to twelve age, gender and education matched normal subjects. Participants were requested to generate, out loud, scripts corresponding to everyday activities. Half the scripts were relatively more demanding with respect to temporal representation (understanding the time line of events) and the other half with respect to spatial representation (understanding the layout of the actions in space). These two conditions were further broken down into conditions of high and low demands on working memory (reciting the scripts backwards versus forward). The frontal lobe patients enunciated significantly fewer actions overall. They were also significantly more impaired than the normal participants on all tasks with high demands on working memory, and more often, high temporal demands (sequencing and perseverative errors). The parietal lobe patients had significant difficulty in sequencing in all conditions, and manifested no perseveration. Though script generation tasks have been primarily associated with frontal lobe function until now, consideration should be given to the type of activity being scripted as a function of relative demands on spatial or temporal representation, as well as working memory, and the contributions of other lobes ought to be taken into consideration.

Cardiovascular and metabolic responses to fasting and thermoneutrality in Ay mice.

Several lines of evidence support a role for reduced melanocortin signaling in the regulation of metabolic rate and cardiovascular function during negative energy balance. We tested the hypothesis that agouti yellow (B6.Cg-A(y)) mice would exhibit blunted physiologic responses to fasting and thermoneutrality. Male B6.Cg-A(y) mice (A(y); n=11, 34+/-2 g) and lean B6 littermates (B6; n=7, 26+/-2 g) were implanted with telemetry devices and housed in metabolic chambers (T(a)=23 degrees C) to determine the effects of a 24-h fasting and exposure to thermoneutrality (T(a)=30 degrees C) on mean arterial pressure (MAP), heart rate (HR), AP and HR variability (time and frequency domain), oxygen consumption (VO(2)), and locomotor activity. A(y) mice exhibited elevated baseline light-period MAP (A(y): 113+/-4; B6: 99+/-3 mm Hg) and VO(2) (A(y): 1.82+/-0.08 vs. B6: 1.45+/-0.13 ml/min) with no difference in HR (A(y): 530+/-12 vs. B6: 548+/-19 bpm). At 12-24 h after food removal, A(y) mice displayed normal fasting-induced bradycardia (A(y): -106+/-12; B6: -117+/-19 bpm) and reduction in VO(2) (A(y): -0.19+/-0.04 vs. B6: -0.28+/-0.05 ml/min), but with augmented hypotension (A(y): -9+/-2 vs. B6: -0.5+/-2 mm Hg) and blunted hyperactivity (A(y): 27+/-23 vs. B6: 122+/-42 m/11 h). Fasting was associated with increased HR variability in both time and frequency domain in B6 but not A(y) mice. Exposure to thermoneutrality produced comparable reductions in MAP, HR, and VO(2) in both strains. We conclude that inhibition of melanocortin signaling is not requisite for, but participates in, the metabolic and cardiovascular responses to negative energy balance.

Up-regulation of glutamate receptors is associated with LTP defects in the early stages of diabetes mellitus.

AIMS/HYPOTHESIS: Recent studies involving electrophysiology and immunolabelling indicate that short-term insulin treatment of hippocampal neurons in culture induces changes in glutamate receptor function, suggesting that this receptor system can be altered on a relatively rapid time scale during diabetic conditions. To investigate this hypothesis, we examined whether brain glutamate receptors and long-term potentiation are altered in the early stages of diabetes mellitus in non-obese diabetic mice, a genetic model of Type I (insulin-dependent) diabetes mellitus. METHODS: In vitro receptor autoradiography and immunoblotting were used to study the impact of diabetes on brain glutamate receptors. From an electrophysiological point of view, field potential recordings were also examined in area CA1 of hippocampal slices to determine the influence of diabetes on long-term potentiation. RESULTS: Quantitative autoradiographic analysis revealed enhanced 3H-glutamate binding to several brain regions of diabetes mice, with maximal increases in the cerebral cortex and hippocampus. Saturation kinetics within the cerebral cortex disclosed that this change of 3H-glutamate was possibly due to an increase in the maximal number of N-methyl- D-aspartate binding sites, an interpretation that was corroborated by Western blot analysis of N-methyl- D-aspartate 2A subunits. Impairment in the expression of hippocampal long-term potentiation was also observed in diabetic mice, while the failure to elicit synaptic potentiation was prevented by insulin treatment. CONCLUSION/INTERPRETATION: Because glutamate receptors are thought to be involved in several degenerative processes, our results suggest that up-regulation of these receptors in the early stages of diabetes could represent an important mechanism underlying neurological complications within the brain of diabetic patients.

T cell receptor Vbeta gene usage in Thai children with dengue virus infection.

T lymphocyte activation during dengue is thought to contribute to the pathogenesis of dengue hemorrhagic fever (DHF). We examined the T cell receptor Vbeta gene usage by a reverse transcriptase-polymerase chain reaction assay during infection and after recovery in 13 children with DHF and 13 children with dengue fever (DF). There was no deletion of specific Vbeta gene families. We detected significant expansions in usage of single Vbeta families in six subjects with DHF and three subjects with DF over the course of infection, but these did not show an association with clinical diagnosis, viral serotype, or HLA alleles. Differences in Vbeta gene usage between subjects with DHF and subjects with DF were of borderline significance. These data suggest that the differences in T cell activation in DHF and DF are quantitative rather than qualitative and that T cells are activated by conventional antigen(s) and not a viral superantigen.

[Lack of conviction about vaccination in certain Quebec vaccinators]. / Manque de conviction face à la vaccination chez certains vaccinateurs québécois.

A questionnaire was mailed to all vaccinators in Quebec in 1998. The objective of this survey was to document vaccinators' attitudes, knowledge, and practices related to vaccination. Vaccinators generally believe in the security, efficacy and usefulness of vaccines given to young children. However, 41% of nurses do not fully agree with these opinions. More than 94% of pediatricians completely disagree that "certain practices (homeopathy, good eating habits and a healthy lifestyle) can eliminate the need for vaccination", compared with 85% of general practitioners and only 60% of nurses. Less than 25% of doctors recall children who are late in getting their immunizations; approximately 45% of vaccinators are in complete agreement with simultaneous injections of two vaccines; many circumstances are incorrectly seen as contra indications for vaccination. Public health authorities should target systematic interventions towards vaccinators to improve this situation and to increase nurses' conviction regarding the benefits of vaccination.

The role of human papillomavirus deoxyribonucleic acid assay and repeated cervical cytologic examination in the detection of cervical intraepithelial neoplasia among human immunodeficiency virus-infected women. Cervical Disease Study Group of the American Foundation for AIDS Research Community Based Clinical Trials Network.

OBJECTIVES: We sought to measure the characteristics of a quantitative human papillomavirus deoxyribonucleic acid assay and repeated cervical cytologic examination in screening for cervical intraepithelial neoplasia among human immunodeficiency virus-infected women. STUDY DESIGN: Human immunodeficiency virus-infected women with screening CD4+ lymphocyte counts of < or = 500 cells/mm3 (n = 103) were examined by quantitative human papillomavirus deoxyribonucleic acid assay and serial cervical cytologic examination and by colposcopy with biopsy and endocervical curettage during the course of 1 year. RESULTS: Quantitative measures of total human papillomavirus deoxyribonucleic acid and high-risk human papillomavirus deoxyribonucleic acid were strongly associated with any cervical intraepithelial neoplasia (P = .005) and high-grade cervical intraepithelial neoplasia (P = .0006), but they improved the sensitivity and negative predictive value of baseline screening only slightly when combined with cervical cytologic examination. Incident cervical intraepithelial neoplasia occurred frequently (20%) during 1 year of follow-up and was more common among human papillomavirus-infected women. Repeated cytologic examination identified 60% of women with new cervical intraepithelial neoplasia. CONCLUSION: Human immunodeficiency virus-infected women with at least mild immunosuppression have a high incidence of cervical intraepithelial neoplasia, which warrants close follow-up. Those with high baseline human papillomavirus deoxyribonucleic acid levels may be at the highest risk for incident cervical intraepithelial neoplasia.

Identification of a crucial energetic footprint on the alpha1 helix of human histocompatibility leukocyte antigen (HLA)-A2 that provides functional interactions for recognition by tax peptide/HLA-A2-specific T cell receptors.

Structural studies have shown that class I major histocompatibility complex (MHC)-restricted peptide-specific T cell receptor (TCR)-alpha/betas make multiple contacts with the alpha1 and alpha2 helices of the MHC, but it is unclear which or how many of these interactions contribute to functional binding. We have addressed this question by performing single amino acid mutagenesis of the 15 TCR contact sites on the human histocompatibility leukocyte antigen (HLA)-A2 molecule recognized by the A6 TCR specific for the Tax peptide presented by HLA-A2. The results demonstrate that mutagenesis of only three amino acids (R65, K66, and A69) that are clustered on the alpha1 helix affected T cell recognition of the Tax/HLA-A2 complex. At least one of these three mutants affected T cell recognition by every member of a large panel of Tax/HLA-A2-specific T cell lines. Biacore measurements showed that these three HLA-A2 mutations also altered A6 TCR binding kinetics, reducing binding affinity. These results show that for Tax/HLA-A2-specific TCRs, there is a location on the central portion of the alpha1 helix that provides interactions crucial to their function with the MHC molecule.

Efficacy and safety of iron sucrose for iron deficiency in patients with dialysis-associated anemia: North American clinical trial.

Iron sucrose has been used to provide intravenous (IV) iron therapy to patients outside the United States for more than 50 years. In a multicenter North American clinical trial, we determined the efficacy and safety of iron sucrose therapy in patients with dialysis-associated anemia, evidence of iron deficiency, and below-target hemoglobin (Hgb) levels despite epoetin therapy. Evidence of iron deficiency included a transferrin saturation (Tsat) less than 20% and ferritin level less than 300 ng/mL, and below-target Hgb levels included values less than 11.0 g/dL. We administered iron sucrose in 10 doses, each administered undiluted as 100 mg IV push over 5 minutes, without a prior test dose. We assessed efficacy by determining the subsequent change in Hgb, Tsat, and ferritin values. We assessed safety by recording blood pressure and adverse events after iron sucrose injection and comparing results with those for the same patients during an observation control period. Results showed a significant increase in Hgb level that was first evident after three doses of iron sucrose and persisted at least 5 weeks after the 10th dose. Tsat and ferritin levels also increased significantly and remained elevated. In 77 enrolled patients, including those with previous iron dextran sensitivity, other drug allergies, or concurrent angiotensin-converting enzyme inhibitor use, we saw no serious adverse drug reactions and no change in intradialytic blood pressure associated with iron sucrose administration. We conclude that iron sucrose injection administered as 1,000 mg in 10 divided doses by IV push without a prior test dose is safe and effective for the treatment of iron deficiency in patients with dialysis-associated anemia.

Characterization of cytohesin-1 monoclonal antibodies: expression in neutrophils and during granulocytic maturation of HL-60 cells.

ADP-ribosylation factors (Arf) are small GTP-binding proteins involved in vesicular transport and the activation of phospholipase D (PLD). The conversion of Arf-GDP to Arf-GTP is promoted in vivo by guanine nucleotide exchange factors such as ARNO or cytohesin-1. In order to examine the expression of ARNO and cytohesin-1 in human granulocytes, we generated specific polyclonal and monoclonal antibodies (mAbs). We also overexpressed GFP-ARNO and GFP-cytohesin-1 in RBL-2H3 cells to characterize the specificity and the ability of cytohesin-1 mAbs to immunoprecipitate cytohesin-1. Among the hybridomas secreting cytohesin-1 mAbs, only the clones 2E11, 1E4, 3C8, 6F5, 4C7, 7A3 and 8F7 were found to be specific for cytohesin-1. Furthermore, mAb 2E11 immunoprecipitated GFP-cytohesin-1 but not GFP-ARNO under native conditions. In contrast, mAbs 5D8, 4C3, 2G8, 6G11, 4C3, 6D4, 7B4 and 6F8 detected both cytohesin-1 and ARNO as monitored by immunoblotting. Although mAb 6G11 detected both proteins, this antibody immunoprecipitated GFP-ARNO but not GFP-cytohesin-1 under native conditions. Another antibody, mAb 10A12, also selectively immunoprecipitated GFP-ARNO under native conditions, but the epitope recognized by this mAb is unlikely to be linear as no signal was obtained by immunoblotting. Immunoprecipitation with a cytohesin-1 polyclonal antibody and blotting with cytohesin-1 specific mAbs revealed that cytohesin-1 is highly expressed in neutrophils. Cytohesin-1 can be detected in HL-60 cells but the endogenous protein levels were low in undifferentiated cells. Using the specific cytohesin-1 mAb 2E11 we observed a marked increase in levels of cytohesin-1 expression during dibutyryl-cyclic AMP-induced granulocytic differentiation of HL-60 cells. These data suggest that cytohesin-1, which may have important functions in neutrophil physiology, can be useful as a potential marker for granulocytic differentiation.