The Timed Up and Go test measures the time a person needs to stand up from a chair, walk 3 m at a comfortable speed, turn around, walk back, and sit down. The test is internally consistent, reliable, valid, and responsive (Lin et al 2004, Mathias et al 1986, Morris et al 2001). The 10 m Walk test can

buy Lenvatinib be used in people able to walk independently with or without walking aids and/or orthoses. The test is reliable, valid and responsive (Garraway et al 1980). The data on outcome measures were collected by an independent, blinded assessor. Data were collected at three assessment points: at baseline, after the 6-week intervention period, and at a follow-up assessment 3 months after randomisation. In order to reduce the influence of fluctuating performance associated with the on/off periods that characterise Parkinson’s disease, data were collected on three separate days for each of the three assessment points and on each day each test was performed three times. At each assessment point, the three days of data collection were scheduled within a 2-week period: during the two weeks before the intervention started (Week −1 to 0), after the intervention period (Week 7–8) and

at the follow-up assessment (Week 12–13). For each patient we used the mean score on each measure for the measurement period. Potentially this was the mean of nine values although some patients completed fewer measures. Neratinib cost The visual analogue scale was measured only once in each assessment period. Florfenicol The calculation of the sample size was based on the visual analogue scale outcome. We sought a difference between the two groups of 2 cm on the 0 to 10 cm visual analogue scale.

In this sample size calculation, we used a standard deviation of 2.25 cm and assumed a 50:50 random allocation. There is no literature available on the minimum clinically important difference between groups or the standard deviation in a population with Parkinson’s disease. In pain patients, however, the minimum clinically important change is set at 1.5 cm (Ostelo et al 2008). Since we hypothesised that participants in the control group would not improve we aimed for a 2-cm difference between groups. In other populations the standard deviation on a visual analogue scale is somewhere between 1.5 and 3.0 (Donnelly and Carswell 2002). With the power of this study set at 90% and the level of significance set at 5%, 19 patients in each group were needed to identify a 2-cm difference between groups as statistically significant. Group characteristics at baseline were presented using descriptive statistics: means and standard deviations for continuous variables, and absolute numbers of participants and percentages for categorical variables. Differences between groups with regard to baseline characteristics were judged on clinical relevance (Assmann et al 2000).

This plan included three main pillars: (1) immediate support for seasonal influenza vaccination in countries not yet administering

it; (2) technical cooperation to assist LAC countries in elaborating national pandemic vaccination plans of action; and (3) support in pandemic (H1N1) vaccine acquisition [23]. In May 2009, PAHO mobilized resources to support the use of seasonal influenza vaccine in nine remaining countries and territories in the Region yet to have introduced the vaccine2. In July 2009, WHO’s Strategic Advisory Group of Experts (SAGE) made their first recommendations on find more pandemic vaccination target groups [9]. One month later, PAHO’s Technical Advisory Group (TAG) endorsed these recommendations, but due to expected vaccine scarcity, TAG emphasized the vaccination of individuals with chronic medical conditions and pregnant women in order to reduce morbi-mortality. TAG also promoted vaccinating health-care workers to protect critical health infrastructure [24]. In the event that more vaccine became available, TAG recommended

expanding target populations, vaccinating groups AUY-922 manufacturer such as school children to reduce community transmission [9] and [24]. PAHO prepared comprehensive technical guidelines which included topics such as defining target populations; vaccination strategies; planning and micro-planning; vaccination safety, including regulatory considerations, ESAVI surveillance, risk communication and crisis planning; vaccine deployment; and vaccination waste management [23]. PAHO also developed separate expanded guidelines on ESAVI surveillance and management [25]. Country

training workshops were conducted between October and November 2009. Pandemic influenza (H1N1) vaccine was acquired in LAC through three mechanisms: (1) purchase through PAHO’s Revolving Fund (RF); (2) direct purchase from vaccine manufacturers; and (3) WHO donation. Some countries used more than one mechanism. In September 2009, almost the RF opened a bid solicitation for approximately 400 million doses of pandemic influenza (H1N1) vaccine. This amount was based on a prior PAHO survey to Member States and not yet knowing whether one or two doses would be required. Sub-regional economic integration systems, such as the Union of South American Nations (UNASUR), supported countries’ use of the RF for pandemic influenza (H1N1) vaccine purchase based on the benefits of collective group negotiation [15] and [26]. Approximately 20.5 million doses of pandemic (H1N1) vaccine from different manufacturers were procured on behalf of 24 LAC countries/territories, including 16.9 million doses of un-adjuvanted vaccines (82.3%) and 3.6 million (17.7%) adjuvanted doses.

These strategies have produced striking reductions in the reported number of human malaria cases in Thailand over the past 30 years, although there have been regional differences with respect to the extent of the reduction. Epidemiological evidence of declining numbers of cases suggest that control measures may be able to produce substantial reductions Enzalutamide manufacturer in local parasite effective population sizes of malaria parasite species, which in turn might cause reduction in the level of parasite

polymorphism. Thus, after extensive mobilization of non-vaccine control measures, a local population may have sufficiently reduced polymorphism that a location-specific vaccine might be feasible and effective. We tested the hypothesis that control measures can induce a loss of polymorphism at antigen-encoding loci by examining data on numbers of P. falciparum and P. vivax infections and nucleotide sequence polymorphism at selected antigen-encoding loci in two areas of Thailand. We compared data from

two different regions: (1) Tak Province, in northwestern Thailand, along the border of Myanmar (henceforth NW); and (2) from Yala and Narathiwat Provinces in southern Thailand (henceforth South; Fig. 1). Reported cases of malaria have declined sharply in the South over the ERK inhibitor price past three decades, but less sharply in the NW [19] and [21]. By comparing sequence polymorphism at antigen-encoding loci, we tested the hypothesis that the more severe decline in malaria cases in the South has been accompanied by a reduction in polymorphism at these vaccine-candidate loci. We randomly recruited blood samples from symptomatic malaria patients from northwestern (Tak Province) and southern Thailand (Yala and Narathiwat Provinces) collected during 1996–1997 for P. falciparum samples and 2006–2007 for both P. falciparum and P. vivax samples. The ethical aspects of this study have been approved by the Institutional Review Board of Faculty of Medicine, Chulalongkorn University. DNA was extracted from either venous blood samples using QIAamp kit (Qiagen, Hilden, Germany) or finger-pricked blood spotted onto filter

paper. We excluded multiple clone infections of P. falciparum isolates by genotyping of polymorphic block 2 of the merozoite surface protein-1 why (Pfmsp-1) and the central repeat region of the merozoite surface protein-2 (Pfmsp-2) genes as described by others [22]. Likewise, genotyping of P. vivax isolates was performed using the highly polymorphic block 6 of the merozoite surface protein-1 (Pvmsp1) [23]. Further, samples showing superimposed eletropherogram signals during DNA sequencing were also excluded from analysis. The complete nucleotide sequences of P. falciparum csp and msp-2 and of P. vivax msp-1, ama-1 and msp-4 were obtained by using respective forward and reverse primers for each gene as described previously [10], [12], [19], [23] and [24]. Sequences of P.

5 (Roche Diagnostic System, Branchburg, NJ, USA) was also performed on all participants

at enrollment to confirm HIV infection by polymerase-chain-reaction (PCR). The PCR result was taken as the definitive result for infant HIV infection, and all positive BMS777607 PCR tests were repeated for verification. In this report, infants whose HIV antibody test was negative but PCR test was positive were considered HIV-infected, which differs from our previous report of this trial where these infants were not classified as HIV-infected [14]. The presence of HIV antibody in PCR-negative children indicated HIV exposure without HIV infection. Children were also tested for HIV (both antibody and PCR) at 9, 12, and 18 months from enrollment (until the study ended) to record acquisition of new HIV infection. The same HIV testing algorithm as above was used. The CD4 T-lymphocyte percentage (CD4%) was obtained for all HIV-infected infants at enrollment. All HIV-exposed and -infected children were referred for appropriate HIV care and treatment (cotrimoxazole if HIV-exposed, and cotrixomazole and antiretroviral treatment if HIV-infected) at local comprehensive care clinics focused on managing Trametinib price patients with HIV infection. Voluntary counseling and testing was offered to mothers of HIV-exposed and -infected infants. Nutritional status of HIV-infected and HIV-exposed

infants was assessed by clinicians throughout the trial, and access to food supplement programs was facilitated, as needed. Infants who were underweight, had marasmus, were wasted, and/or directed to be given nutritional supplements were recorded as malnourished, and were enrolled/retained in the study as long as the subject met the inclusion/exclusion criteria. An independent, unblinded data safety monitoring board (DSMB), composed of at least one representative person (not affiliated with the trials) from each of the participating countries, as well as a number of experts and a biostatistician, Thiamine-diphosphate kinase monitored all SAE’s for all five country sites in these multicenter trials. The DSMB met on a regular

basis and reviewed all SAES, including intussusception and deaths in an unblinded fashion. The DSMB evaluated all SAEs and the safety data from the intensive safety surveillance cohort including all adverse events, with a focus on vomiting, diarrhea and elevated temperature, by vaccination group and HIV status, and provided guidance as to whether modifications should be made regarding enrollment of HIV-infected children or children of unknown HIV status. The DSMB provided reports to all of the ethical review committees and institutional review boards, the principal investigators in each of the five countries, and the sponsors, PATH and Merck. For all safety evaluations, the analysis included all participants who had received at least 1 dose of vaccine/placebo and who were followed for safety.

For the CTL assay, frozen PBMC samples from each time point were thawed and cultured for 24 h prior to use in complete medium consisting of RPMI 1640 (Invitrogen) supplemented with

nonessential amino acids (Invitrogen), penicillin/streptomycin (Invitrogen) and 10% heat-inactivated fetal bovine serum (FBS; Invitrogen) at 37 °C, in a 5% CO2 incubator. Autologous tumor cells were maintained in a 6 well plate coated with matrigel matrix (BD bioscience, San Jose, CA) in DMEM (Invitrogen) supplemented with penicillin/streptomycin and 10% FBS. The day of the assay, effector cells were incubated with target cells in complete RPMI 1640 media in 12 × 75 mm Facs tubes (BD bioscience) GSK1349572 cost for 5 h at 37 °C in 5% CO2. The effector/target cell ratio used was 10:1 with 1 × 105 PBMCs. Effector cells from each time point were cultured alone (no targets) as control for spontaneous degranulation and IFNγ elaboration. A representative background degranulation response is shown in Fig. 2B, left panel. FITC conjugated anti-CD107b

antibody (AbD Serotec, Oxford, UK) or IgG1 isotype control (AbD Serotec) was added at the beginning of the co-culture. After a 1-h coincubation, Monensin (1:100 dilution; BD Biosciences) and Brefeldin A (3 μg/ml final concentration; eBioscience) were added check details for the last 4 h of incubation [26]. Following incubation, cell suspensions were washed with ice-cold PBS and stained for with anti-CD8 TCL antibody conjugated to Alexa Fluor 700 (AbD Serotec) for 30 min at 4 °C. Samples were then fixed and permeabilized using BD Cytofix/Cytoperm kit (BD bioscience) and stained for intracellular IFNγ with the cross-reactive anti-bovine IFNγ antibody conjugated to PE (AbD Serotec). For detection of Tregs, frozen PBMCs were thawed and added at 1 × 105 in 12 × 75 mm Facs tubes. Cell surface staining was done using Pacific Blue-conjugated anti-dog CD4 antibody (AbD Serotec) or IgG1 isotype control (AbD Serotec) at 4 °C for 30 min. Following incubation, cell suspensions were

washed with cold PBS and resuspended in fixation permeabilization working solution (Foxp3 staining buffer set, eBioscience) overnight. The next day cells were washed with permeabilization buffer (Foxp3 staining buffer set, eBiosceince) followed by intracellular staining with a cross-reactive anti-mouse Foxp3 PeCy-5 conjugated antibody (eBioscience) at 4 °C for 30 min [29]. Samples were then washed and resuspended in PBS for flow cytometric analysis. Analysis gates were set on the live lymphocyte population based on forward and side scatter characteristics. All flow cytometric analysis was performed on a FACS Canto II flow cytometer (BD Biosciences). A total of 20,000 events were acquired and analyzed using FlowJo software (Tree Star, Ashland, OR). Cultured autologous tumor cells were washed, pelleted, and lysed in RIPA buffer (25 mM Tris–HCl, 0.1% SDS, 1% Triton X-100, 1% sodiumdeoxycholate, 0.

For live attenuated strains containing other disabling

mutations, sustaining colonisation by inclusion of capsule may be a strategy to enhance the immunogenicity of the non-capsular antigens present in the strain and induce protection against invasive disease. The authors are grateful to the staff at the UCL Biological Services Unit for assistance with animal maintenance. This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health’s NIHR Biomedical Research Talazoparib nmr Centre’s funding scheme. JMC was supported by a Clinical Research Training Fellowship from the Medical Research Council (G0700829). “
“The authors regret that there was an error in their paper. The primers reported for cloning the DR2 domain of H. somni IbpA were not DAPT correct. The error was present in the original data. The correct forward and reverse primers used for IbpA DR2 (p. 4507) are as follows: 5′-AGCTCCATGGGAAAATCATCTCCGCAAGAG-3′; 5′-AGCTGGATCCTGATTTTTTTGCCAACTCTTTTAAA-3′. These primers were published in a later paper

by Geertsema RS, Zekarias B, La Franco Scheuch L, Worby C, Russo R, Gershwin LJ, Herdman DS, Lo K, Corbeil LB. IbpA DR2 subunit immunization protects calves against Histophilus somni pneumonia. Vaccine 2011;29:4805–12. “
“The authors wish to update the corresponding author’s contact email to: [email protected]. “
“TB remains one of the world’s most serious infectious diseases and is responsible for more than 2 million deaths each year [1]. The only available vaccine, Mycobacterium bovis Bacille Calmette Guérin (BCG), confers some protection against disseminated TB in childhood but is largely ineffective at protecting against adult pulmonary disease [2]. Thus, a more effective TB vaccine is urgently needed. New vaccines for TB are assessed on measures

including safety, the ability to confer Isotretinoin protection against Mycobacterium tuberculosis (MTB) challenge in preclinical animal models, and the ability to induce an antigen specific IFN-γ immune response. Although there is no immune correlate of protection for TB, impairment of IFN-γ and IL-12 signalling in humans is associated with susceptibility to mycobacterial disease and the measurement of antigen specific IFN-γ remains the primary immune outcome in Phase I testing of new TB vaccine candidates [3]. We have previously reported that recombinant Modified Vaccinia virus Ankara (MVA) expressing antigen 85A from MTB (MVA85A) is well-tolerated and enhances the frequency of antigen-specific IFN-γ producing T cells in adults, children and infants previously vaccinated with BCG [4], [5], [6], [7], [8], [9] and [10]. We have also shown that antigen specific T cells induced by MVA85A are highly polyfunctional, and can express IFN-γ, TNF-α, IL-2, MIP1-β and IL-17 [11] and [12]. However, to date we have not performed any dose-finding studies in UK adults.

Recently, New Delhi metallo-β-lactamase 1 (NDM-1) has been identified in Gram −ve Enterobacteriaceae which is resistance to carbapenam. 6 This prompted us to syntheses a novel series of sulfonamides based on anthranilic acid (A1-A19). The newly synthesized compounds were characterized by using IR, 1H NMR, 13CNMR and Mass Spectrometry (unpublished data). This selleck article documents in vitro antibacterial activity of the synthesized

compounds against 19 Gram −ve and 2 Gram +ve (Staphylococcus aureus ATCC25923 and Enterococcus faecalis) pathogenic bacteria, and the minimum inhibitory concentration (MIC) determined by agar dilution method. 2-(substituted sulfonamido) benzoic acid derivatives (A1-A19) were synthesized by reacting 2-aminobenzoic acid (anthranilic acid) with different alkyl, aryl and substituted aryl sulfonyl chlorides. IR, NMR and MS data of synthesized compounds are in agreement with their structures (unpublished data). Determination of MIC for the synthesized compounds was carried out as described by Wiegand et al using Mueller–Hinton agar medium against 19 Gram −ve and 2 Gram +ve organisms.7 About 50 mg/ml solutions of test compounds (A1-A19) as well as sulphamethoxazole were prepared in DMSO. From these stock solutions, serial dilutions of the compounds (50,000, 25,000 – 781.25 μg/ml) were prepared. Then, 16 ml of agar medium (at

50 °C) was added to bring the final concentrations in the range of 2941, 1470.5 – 45.95 μg/ml and transferred into petri dishes. Suspensions of each microorganism were prepared find more to contain approximately 106 colony forming units per ml and applied to plates containing serially diluted compounds to be tested; and incubated at 37 °C for overnight these (approx. 18–20 h). At the end of the incubation period,

the MIC values were determined. All determinations were done in triplicates and average was taken as final reading. Sulphamethoxazole was used as positive control, and DMSO as negative control. Minimum inhibitory concentration (MIC) is defined as the lowest concentration that inhibits the visual growth of a microorganism. MIC values of the tested compounds are presented in Table 1. To our knowledge, this is the first report on the antibacterial activity of the novel series of 2-(substituted sulfonamido) benzoic acid. The negative control, DMSO, used for the preparation of test and standard solution did not show any inhibition against the tested organisms. MIC values of the standard against different microorganisms were presented in Table 1, and they are comparable with the values published by Pandeya et al.8 Tested compounds showed mild to moderate antibacterial activity against tested organisms. Compounds, A5, A12, A15, A18 and A19 were showed moderate antibacterial activity against atypical Escherichia coli. Whereas, compounds with p-chloro (A14, Fig. 2) and p-fluoro (A17) phenyl substitutions showed good antibacterial activity with MIC values 183.81 μg/ml and 367.

Demographically, the coming years are expected to show a reduced demand for paediatric vaccines due to lower birth rates. On the other hand, the increase in life expectancy means that the population over 60 years of age will represent about 40% of the total population in 2040. This evolution

has an important bearing on vaccine needs and production plant capacity. Indeed, using 15 μg of antigen per dose as anticipated for a non-adjuvanted split inactivated vaccine, Butantan would not be able to meet the demand of the Ministry of Health for seasonal influenza vaccine. Butantan’s production plant will operate for 4–6 months per year to produce southern hemisphere influenza vaccine, and would remain idle for a full semester. It could therefore be envisaged to produce the northern hemisphere formulation during Selleck Everolimus these inactive months, which could be provided to other governments for immunization of their target ZD1839 manufacturer groups, in exchange for southern hemisphere vaccine. Approval for this strategy remains to be sought from the technology provider (sanofi pasteur). There are further complexities in the timing and formulation of influenza

vaccine in Brazil. Vaccination in the north and north-east currently takes place as elsewhere in the country in April, yet this is four months after the local seasonal influenza peak. Analysis of an epidemiological survey suggests that vaccination should take place earlier in this region. The exact transmission pathway that determines the origin of the virus is not clearly understood, nor the onset of a significant drop in temperature that sparks influenza incidence. Even if we could use the northern hemisphere formulation in this region, our inability to meet the demand for the southern hemisphere vaccine would not change, as the north and north-eastern regions only needs 2–5 million doses per year. Further,

the difference in protection using one or the other formulation is not well defined [6] as this will depend on the extent to which the viruses have drifted. Butantan considers that the best option to address potential Astemizole shortages of influenza vaccine is antigen sparing through the use of adjuvants. We first intended to formulate our influenza vaccines using aluminium hydroxide. We anticipated that by doing this we would not only be able to maximize production capacity by reducing the HA antigen content per dose, but also to lower the price of the vaccine to make it accessible for the least developed countries. Unfortunately, results of many published animal and clinical assays, mostly for H5N1, show that immunopotentiation by aluminium hydroxide is at best moderate, and most likely dependent on the source of aluminium salts, although the recent establishment of the mechanism of potentiation of aluminium salts [7] should lead to the improved performance of aluminium preparations.

C’est particulièrement le cas pour les diurétiques, et en particulier l’hydrochlorothiazide susceptible de perturber la libido, d’induire une dysfonction érectile et une sécheresse vaginale. La spironolactone peut avoir aussi des effets défavorables aussi bien chez l’homme que chez la femme. L’analyse des effets indésirables des différentes classes médicamenteuses de traitement cardiaque chez les Selleckchem Regorafenib hommes montre

que les médicaments les plus délétères sur la fonction érectile sont les antihypertenseurs centraux et les diurétiques, bien plus que les bêtabloqueurs ; les antagonistes calciques et les IEC n’ayant pratiquement pas d’effet. Il existerait même un discret effet favorable des alpha-bloquants et des antagonistes des récepteurs de l’angiotensine II [30]. Il est en effet très important de ne pas diaboliser les bêtabloquants qui peuvent certes être responsables de dysfonction érectile ou, peut-être surtout, d’aggravation de la dysfonction érectile préalable selleck chemicals à l’infarctus (liée à la dysfonction endothéliale). Il est probable qu’il y a là une part d’effet placebo dans la mesure où l’effet délétère des bêtabloquants

est largement diffusé et qu’il est spécifié dans les notices des médicaments. Les études expérimentales, notamment contre placebo, montrent finalement que l’effet défavorable des bêtabloquants sur la fonction érectile est plutôt moins important que celui qui leur est habituellement attribué [32] and [33]. On peut ADP ribosylation factor citer ici l’éventuel intérêt du nébivolol dont le mode d’action est original, avec un effet vasodilatateur périphérique via la voie du NO qui est sans doute le bêtabloquant le moins délétère sur la fonction érectile, même s’il n’a pas d’AMM spécifique en post-infarctus [34]. Il est bien sûr essentiel de proposer une prise en charge thérapeutique au patient cardiaque ayant une dysfonction érectile. La démarche doit débuter

par la recherche de causes organiques avant d’évoquer d’éventuels effets médicamenteux indésirables, et un travail en équipe, notamment avec une unité d’urologie compétente, est indispensable. Ce n’est qu’en cas d’absence d’anomalie qu’il faudra proposer une prise en charge médicamenteuse. L’érection est un phénomène sous la dépendance du monoxyde d’azote secrété au niveau de l’endothélium. Ce monoxyde d’azote va avoir pour effet de relâcher la musculature lisse vasculaire et d’aboutir à l’érection. Le monoxyde d’azote stimule la guanylate et l’adénylate cyclase avec augmentation des taux intracellulaires de GMP et d’AMP cycliques aboutissant à la vasodilatation. Les phosphodiestérases dégradent le GMP cyclique diminuant ainsi la vasodilatation. Les inhibiteurs de phosphodiestérases de type 5 agissent en maintenant des taux de GMP cycliques élevés, favorisant la vasodilatation et donc l’érection (figure 2).

This analysis of IgA responses from 3 clinical studies in young

children confirms that LAIV induces measurable strain-specific IgA and demonstrates that these responses are associated with protection from subsequent influenza illness. IgA response rates were similar among subjects with and without prior exposure to influenza, as measured by baseline HAI antibody. For LAIV recipients, postvaccination strain-specific to total IgA ratios were consistently higher among those without influenza illness; thus higher amounts of strain-specific IgA appeared to protect the children from developing BTK inhibitor influenza illness. These findings are expected given that LAIV is a mucosal vaccine; however, they have not been previously demonstrated in large clinical studies. The association

between nasal strain-specific IgA and the incidence of influenza illness was consistently observed in years 1 and 2. The increased IgA response following 2 doses versus 1 dose of vaccine in study 3 also demonstrates that LAIV-induced mucosal antibody responses can be boosted with revaccination, consistent with data demonstrating enhanced clinical efficacy following revaccination [20]. However, the observed increases in IgA among LAIV recipients were of moderate magnitude and highly variable and substantial responses were observed among placebo recipients. This high variability is expected given that variation in nasal secretions and sample collection can lead to significant variability in sample volume PKC inhibitor and quality; this phenomenon explains the response rates observed among placebo almost recipients. As a result, the current data demonstrate that evaluations of strain-specific IgA responses in LAIV versus placebo recipients can provide a positive marker of vaccine-induced immunity but do not fully explain LAIV-induced

protection from influenza illness. A previous study by Boyce et al. demonstrated higher postvaccination IgA responses among pediatric LAIV recipients than the current analysis; IgA responses were observed in 62–85% of LAIV recipients compared to 0–33% of placebo recipients [27]. The higher response seen may be due to the small sample, more consistent sampling in a single study center, or slight differences in assay methodology. Additionally, Boyce et al. evaluated IgA an average of 82 days following vaccination, in contrast to the 56 days used in the studies presented here. Data from study 3 suggest that LAIV-induced strain-specific IgA responses continue to increase over time, as responses in subjects who received a single dose of LAIV were more apparent at 2 months versus 1 month after vaccination. In adults vaccinated with LAIV, IgA responses have been less consistent and more modest than the responses observed in children. In previous exploratory studies conducted in adults, IgA response rates in LAIV recipients ranged from 10% to 40%, and in many cases, responses were not different from those observed among placebo recipients.