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Selected AbstractsResponse of lung ,, T cells to experimental sepsis in miceIMMUNOLOGY, Issue 1 2004Mark Hirsh Summary ,, T cells link innate and adaptive immune systems and may regulate host defence. Their role in systemic inflammation induced by trauma or infection (sepsis) is still obscured. The present study was aimed to investigate functions of lung ,, T cells and their response to experimental sepsis. Mice were subjected to caecal ligation and puncture (CLP) to induce sepsis and acute lung injury (ALI), or to the sham operation. Animals were killed 1, 4, and 7 days postoperatively; lungs were examined by histology, and isolated cells were studied by flow cytometry. Absolute number of ,, T cells progressively increased in lungs during sepsis, and reached a seven-fold increase at day 7 after CLP (3·84 ± 0·41 × 105/lung; P,=,0·0002 versus sham). A cellular dysfunction was revealed one day after CLP, as manifested by low cytolytic activity (22·3 ± 7·1%; P,<,0·05 versus sham), low interferon-, (IFN-,; 8·5 ± 2·5%; P,<,0·05 versus control) and interleukin-10 (IL-10) expression, and high tumour necrosis factor-, expression (19·5 ± 1·7%; P,<,0·05 versus control). The restoration of cytotoxicity, and increase in IFN-, and IL-10 expression was observed at day 7 of CLP-induced sepsis. In summary, our results demonstrate significant progressive accumulation of ,, T cells in lungs during CLP-induced ALI. The temporary functional suppression of lung ,, T cells found early after CLP may influence the outcome of sepsis, possibly being associated with uncontrolled inflammatory lung damage. [source] Influence of maternal carbohydrate intake on fetal movements at 14 to 16 weeks of gestationPRENATAL DIAGNOSIS, Issue 2 2003Israel Goldstein Abstract Objective Ultrasonographic assessment of fetal movements at 14 to 16 weeks of gestation before and after maternal oral intake of carbohydrate. Design Thirty consecutive healthy pregnant women between 14 and 16 weeks of gestation were scanned transvaginally. Real-time ultrasound recordings of 20 min duration were performed in the fasting state and after an oral intake of 110 g of glucose. The number of fetal movements, body and limb movements and breathing movements were evaluated. Fetal movements were quantified using a digital chronometer, and the percentage of time spent moving and the rate of movements per minute were then calculated. Data was statistically analyzed using the simple and Wilcoxon paired t -test. Results Absolute number of fetal movements, body movements, rotation movements, time spent moving and rate of movements per minute showed a statistically significant increase after maternal intake of carbohydrate (p < 0.0001). Conclusions Maternal oral intake of 110 g of carbohydrate significantly increases fetal movements at 14 to 16 weeks of gestation, thus allowing better ultrasonographic viewing of the fetus. Copyright © 2003 John Wiley & Sons, Ltd. [source] Evaluation of the Personal Dental Services (Wave 1) for Lambeth, Southwark and Lewisham Primary Care Trusts , Part 1: Retrospective analyses of registration data and access issuesJOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 3 2005Helen Best BDS MDS PhD Abstract Aim/objective, The purpose of the study was to undertake analyses of registration data for the personal dental services (PDS) of Lambeth, Southwark and Lewisham primary care trusts and relate the analyses to the PDS goal ,of ,increasing ,uptake ,of ,dental services. Method, Secondary analyses of registration statistics provided by the Dental Practice Board were undertaken for both 1 years pre-PDS (October 1997 to September 1998) and post-PDS (October 1998 to March 2003) periods. Three sets of analyses were undertaken to consider different aspects of changing registrations: (1) Absolute numbers of patients registered at each time interval; (2) Rates of change in numbers of patients registered for the entire period after the introduction of PDS; and (3) Rates of change in numbers of patients registered ,for ,the ,most recent 3 years of available data. Results, There was a significant increase in the numbers of children registered under capitation, post-PDS as compared to the pre-PDS level (all ages and both genders combined). Post-PDS, the rate of increase for the children was approximately one additional child per practice per month (0.96, 95% CI 0.41,1.52). Similarly there was a significant trend for increasing adults registrations over time of about two and a half adults per practice per month (2.42, 95% CI 0.90,3.95). There was no evidence of a change in registrations for children or adults in total over the most recent period of 3 years. Conclusions, The analysis of the absolute numbers of registered patients each month indicated that the PDS practices had more children registered than before the implementation of the PDS scheme, but not adults. Overall post-implementation there was a trend for increasing registrations in both children and adults, but the most recent data indicated a plateau effect. Further consideration of facilitators to achieve PDS goals of improved uptake of services is required, particularly as they relate to local contexts. [source] Cellular dynamics in the draining lymph nodes during sensitization and elicitation phases of contact hypersensitivityCONTACT DERMATITIS, Issue 5 2007Jeppe Madura Larsen Background:, The different role of various immunological effector cells in contact hypersensitivity (CHS) is receiving increased attention. During the past decade, the involvement of different cell types in CHS has been investigated by the use of antibody-induced depletion of specific subtypes of immunological cells and by studying knockout mice lacking one or more of these immunological cell populations. Objectives:, To develop a method for studying the collective cellular dynamics of immune cells in the draining lymph nodes during CHS in intact animals. Patients/Methods:, Mice were sensitized and/or challenged with 2,4-dinitrofluorobenzene or oxazolone. Using multi-parameter flow cytometry we determined the proliferation, activation state, and absolute number of helper T cells, cytotoxic T cells, B cells, and natural killer cells in the draining lymph nodes. Results:, The presented method can be applied to evaluate the effect of different contact allergens on various cell populations of the immune system. Conclusions:, Our study support recent findings that several cell types seem to be involved in CHS. [source] Abundance of six tetracycline resistance genes in wastewater lagoons at cattle feedlots with different antibiotic use strategiesENVIRONMENTAL MICROBIOLOGY, Issue 1 2007Nicholas Peak Summary The abundance of six tetracycline resistance genes tet(O), tet(Q), tet(W), tet(M), tet(B) and tet(L), were quantified over time in wastewater lagoons at concentrated animal feeding operations (CAFO) to assess how feedlot operation affects resistance genes in downstream surface waters. Eight lagoons at five cattle feedlots in the Midwestern United States were monitored for 6 months. Resistance and 16S-rRNA gene abundances were quantified using real-time PCR, and physicochemical lagoon conditions, tetracycline levels, and other factors (e.g. feedlot size and weather conditions) were monitored over time. Lagoons were sorted according to antibiotic use practice at each site, and designated as ,no-use', ,mixed-use' or ,high-use' for comparison. High-use lagoons had significantly higher detected resistance gene levels (tetR; 2.8 × 106 copies ml,1) relative to no-use lagoons (5.1 × 103 copies ml,1; P < 0.01) and mixed-use lagoons (7.3 × 105 copies ml,1; P = 0.076). Bivariate correlation analysis on pooled data (n = 54) confirmed that tetR level strongly correlated with feedlot area (r = 0.67, P < 0.01) and ,total' bacterial 16S-rRNA gene level in each lagoon (r = 0.51, P < 0.01), which are both characteristic of large CAFOs. tet(M) was the most commonly detected gene, both in absolute number and normalized to 16S-rRNA gene level, although tet(O), tet(Q) and tet(W) levels were also high in the mixed and high-use lagoons. Finally, resistance gene levels were highly seasonal with abundances being 10,100 times greater in the autumn versus the summer. Results show that antibiotic use strategy strongly affects both the abundance and seasonal distribution of resistance genes in associated lagoons, which has implications on water quality and feedlot management practices. [source] Homeostatic regulation of T effector to Treg ratios in an area of seasonal malaria transmissionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2009Olivia C. Finney Abstract An important aspect of clinical immunity to malaria is the ability to down-regulate inflammatory responses, once parasitaemia is under control, in order to avoid immune-mediated pathology. The role of classical (CD4+CD25+CD127lo/,FOXP3+) Treg in this process, however, remains controversial. Thus, we have characterized the frequency, phenotype and function of Treg populations, over time, in healthy individuals in The Gambia. We observed that both the percentage and the absolute number of CD4+FOXP3+CD127lo/, T cells were higher among individuals living in a rural village with highly seasonal malaria transmission than among individuals living in an urban area where malaria rarely occurs. These CD4+FOXP3+CD127lo/, T cells exhibited an effector memory and apoptosis-prone phenotype and suppressed cytokine production in response to malaria antigen. Cells from individuals exposed to malaria expressed significantly higher levels of mRNA for forkhead box P3 and T-box 21 (T-BET) at the end of the malaria transmission season than at the end of the non-transmission season. Importantly, the ratio of T-BET to forkhead box P3 was remarkably consistent between populations and over time, indicating that in healthy individuals, a transient increase in Th1 responses during the malaria transmission season is balanced by a commensurate Treg response, ensuring that immune homeostasis is maintained. [source] Therapy-induced antitumor vaccination by targeting tumor necrosis factor-, to tumor vessels in combination with melphalanEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2007Lorenzo Mortara Abstract Treatment of tumor-bearing mice with mouse (m)TNF-,, targeted to tumor vasculature by the anti-ED-B fibronectin domain antibody L19(scFv) and combined with melphalan, induces a therapeutic immune response. Upon treatment, a highly efficient priming of CD4+ T cells and consequent activation and maturation of CD8+ CTL effectors is generated, as demonstrated by in vivo depletion and adoptive cell transfer experiments. Immunohistochemical analysis of the tumor tissue demonstrated massive infiltration of CD4+ and CD8+ T cells 6,days after treatment and much earlier in the anamnestic response to tumor challenge in cured mice. In fact, the curative treatment with L19mTNF-, and melphalan resulted in long-lasting antitumor immune memory, accompanied by a mixed Th1/Th2-type response and significant in vitro tumor-specific cytolytic activity. Finally, the combined treatment reduced the percentage and absolute number of CD4+CD25+ regulatory T cells in the tumor-draining lymph nodes of mice responding to therapy, and this was associated with the establishment of protective immunity. These findings pave the way for alternative therapeutic strategies based on the targeted delivery of biological and pharmacological cytotoxic compounds that not only kill most of the tumor cells but, more importantly, trigger an effective and long-lasting antitumor adaptive immune response. [source] CLINICAL STUDY: FULL ARTICLE: Immunomodulating properties of gamma-hydroxybutyrate (GHB), flunitrazepam and ethanol in ,club drugs' usersADDICTION BIOLOGY, Issue 3 2010Simona Pichini ABSTRACT Despite the increasing concern about gamma-hydroxybutyrate (GHB) toxicity in users, no studies have addressed GHB and other club drugs effects on the immune system under controlled administration. Lymphocyte subsets and functional responsiveness of lymphocytes to mitogenic stimulation were measured in 10 healthy male recreational users of GHB who participated in five experimental sessions within the framework of a clinical trial. The study was randomized, double blind, double dummy and cross-over. Drug conditions were: a single oral dose of GHB (40 mg/kg or 60 mg/kg), ethanol (0.7 g/kg), flunitrazepam (1.25 mg) and placebo. Acute GHB produced a time-dependent immune impairment in the first 4 hours after drug administration associated with an increase in cortisol secretion. Although total leukocyte count remained unchanged, there was a significant decrease in the CD4 T/CD8 T-cell ratio, as well as in the percentage of mature T lymphocytes, probably because of a decrease in both the percentage and absolute number of T helper cells. A significant decrease was also observed in natural killer cells and in functional responsiveness of lymphocytes to mitogenic stimulation. Flunitrazepam administration did not produce any change in the immune system, while ethanol intake produced a decrease in B lymphocytes and in lymphocyte proliferative response to mitogens. These results provide the first evidence that GHB intake under a controlled environmental setting impairs the immunological status and confirms the alterations in the immune function caused by ethanol. [source] CNS-irrelevant T-cells enter the brain, cause blood,brain barrier disruption but no glial pathologyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2007Alina Smorodchenko Abstract Invasion of autoreactive T-cells and alterations of the blood,brain barrier (BBB) represent early pathological manifestations of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Non-CNS-specific T-cells are also capable of entering the CNS. However, studies investigating the spatial pattern of BBB alterations as well as the exact localization and neuropathological consequences of transferred non-CNS-specific cells have been thus far lacking. Here, we used magnetic resonance imaging and multiphoton microscopy, as well as histochemical and high-precision unbiased stereological analyses to compare T-cell transmigration, localization, persistence, relation to BBB disruption and subsequent effects on CNS tissue in a model of T-cell transfer of ovalbumin (OVA)- and proteolipid protein (PLP)-specific T-cells. BBB alterations were present in both EAE-mice and mice transferred with OVA-specific T-cells. In the latter case, BBB alterations were less pronounced, but the pattern of initial cell migration into the CNS was similar for both PLP- and OVA-specific cells [mean (SEM), 95 × 103 (7.6 × 103) and 88 × 103 (18 × 103), respectively]. Increased microglial cell density, astrogliosis and demyelination were, however, observed exclusively in the brain of EAE-mice. While mice transferred with non-neural-specific cells showed similar levels of rhodamine-dextran extravasation in susceptible brain regions, EAE-mice presented huge BBB disruption in brainstem and moderate leakage in cerebellum. This suggests that antigen specificity and not the absolute number of infiltrating cells determine the magnitude of BBB disruption and glial pathology. [source] Efficacy of doublecortin as a marker to analyse the absolute number anddendritic growth of newly generated neurons in the adult dentate gyrusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2004Muddanna S. Rao Abstract Doublecortin (DCX), a microtubule-associated phosphoprotein, has been recently utilized as a marker of newly born neurons in the adult dentate gyrus (DG). Nonetheless, it is unknown whether DCX exclusively labels newly formed neurons, as certain granule cells with the phenotype of differentiated neurons express DCX. We addressed the authenticity of DCX as a marker of new neurons in the adult DG by quantifying cells that are positive for 5,-bromodeoxyuridine (BrdU), DCX and both BrdU and DCX in hippocampal tissues of adult rats treated with daily injections of BrdU for 12 consecutive days. We provide new evidence that neurons visualized with DCX immunostaining in the adult rat DG are new neurons that are predominantly born during the 12 days before euthanasia. This is confirmed by the robust expression of BrdU in 90% of DCX-positive neurons in the DG of animals injected with BrdU for 12 days. Furthermore, DCX expression is specific to newly generated healthy neurons, as virtually all DCX-positive cells express early neuronal antigens but lack antigens specific to glia, undifferentiated cells or apoptotic cells. As DCX expression is also robust in the dendrites, DCX immunocytochemistry of thicker sections facilitates quantification of the dendritic growth in newly born neurons. Thus, both absolute number and dendritic growth of new neurons that are generated in the adult DG over a 12-day period can be quantified reliably with DCX immunostaining. This could be particularly useful for analysing changes in dentate neurogenesis in human hippocampal tissues as a function of ageing or neurodegenerative diseases. [source] Cardiovascular Risk Assessment and TriptansHEADACHE, Issue 2004Vasilios Papademetriou MD Identifying the patient for whom triptans are contraindicated because of recognized, diagnosed cardiovascular disease is relatively straightforward. Determining whether a patient with potential unrecognized cardiovascular disease is an appropriate candidate for triptan therapy, however, constitutes a difficult challenge, especially in the absence of a framework for workup of patients. This article discusses the pathophysiology of coronary heart disease and issues involved in assessing cardiovascular risk, and it attempts to provide a framework for cardiovascular risk assessment that can be applied to decisions for prescribing triptans. Current guidelines for cardiovascular risk assessment allow stratification of patients to low, intermediate, or high risk of coronary heart disease events. This framework for risk assessment can be applied to decisions for prescribing triptans. Cardiovascular risk-assessment algorithms discussed elsewhere in this supplement suggest that patients at low risk (1 or no risk factors) of coronary heart disease can be prescribed triptans without the need for a more intensive cardiovascular evaluation. Conversely, patients with established coronary heart disease or coronary heart disease risk equivalents should not be prescribed triptans according to the current prescribing recommendations. Patients at intermediate risk (2 or more risk factors) of coronary heart disease require cardiovascular evaluation before triptans can be prescribed. Current understanding suggests that the risk of future acute coronary events is a function of the absolute number of vulnerable plaques present, a variable that cannot be accurately determined using available technology or risk-prediction models. Cardiovascular risk-assessment guidelines should be evaluated in the context of this limitation. [source] Impact of human immunodeficiency virus 1 infection and inflammation on the composition and yield of cervical mononuclear cells in the female genital tractIMMUNOLOGY, Issue 1pt2 2009Nonhlanhla N. Nkwanyana Summary Cervical cytobrush sampling is a relatively non-invasive method for obtaining mucosal cells from the female genital tract. To define mucosal immune cells sampled by cervical cytobrushing and to validate this approach for local immunity studies, we investigated the impact of human immunodeficiency virus (HIV) status and inflammation on the yield and composition of cervical cytobrush specimens. Cervical cytobrush samples were obtained from 89 chronically HIV-infected and 46 HIV-negative women. The HIV-infected women had significantly higher yields of CD3+, CD45+, CD19+, CD14+, Langerin+ and CD24+ cells than the uninfected women. While cytobrush-derived T cells from uninfected women were predominantly CD4+ (4·2 CD4 : 1 CD8), CD8+ T cells were predominant in HIV-infected women (0·6 CD4 : 1 CD8). The majority of CD4+ and CD8+ T cells from HIV-infected and uninfected women were of the effector memory (CD45RA, CCR7, CD27,) phenotype. HIV-infected women had significantly elevated levels of interleukin (IL)-1,, IL-6 and IL-8 in cervical supernatants compared with uninfected women. We observed a significant positive correlation between T-cell counts and IL-1,, tumour necrosis factor (TNF)-, and IL-12 concentrations. Neutrophil counts correlated significantly with cervical concentrations of IL-1,, TNF-,, IL-8, IL-6 and IL-10. Antigen-presenting cell numbers correlated significantly with TNF-, and IL-12 concentrations. HIV-infected women on antiretroviral therapy had similar levels of cervical lymphocyte infiltration and inflammation to women naïve to therapy. In conclusion, we suggest that inflammation at the cervix and HIV infection are likely to be key determinants in the absolute number of mucosal immune cells recovered by cervical cytobrushing. [source] Sperm function tests and fertilityINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2006R. J. Aitken Summary Traditionally, the diagnosis of male infertility has depended upon a descriptive evaluation of human semen with emphasis on the number of spermatozoa that are present in the ejaculate, their motility and their morphology. The fundamental tenet underlying this approach is that male fertility can be defined by reference to a threshold concentration of motile, morphologically normal spermatozoa that must be exceeded in order to achieve conception. Many independent studies have demonstrated that this fundamental concept is flawed and, in reality, it is not so much the absolute number of spermatozoa that determines fertility, but their functional competence. In the light of this conclusion, a range of in vitro tests have been developed to monitor various aspects of sperm function including their potential for movement, cervical mucus penetration, capacitation, zona recognition, the acrosome reaction and sperm,oocyte fusion. Such functional assays have been found to predict the fertilizing capacity of human spermatozoa in vitro and in vivo with some accuracy. Recent developments in this field include the introduction of tests to assess the degree to which human spermatozoa have suffered oxidative stress as well as the integrity of their nuclear and mitochondrial DNA. Such assessments not only yield information on the fertilizing capacity of human spermatozoa but also their ability to support normal embryonic development. [source] Cytotoxic effects of ,, T cells expanded ex vivo by a third generation bisphosphonate for cancer immunotherapyINTERNATIONAL JOURNAL OF CANCER, Issue 1 2005Kiyoshi Sato Abstract Nitrogen containing-bisphosphonates (N-BPs), widely used to treat bone diseases, have direct antitumor effects via the inactivation of Ras proteins. In addition to the direct antitumor activities, N-BPs expand gd,,T cells, which exhibit major histocompatibility complex-unrestricted lytic activity. BPs accumulate intermediate metabolites which may be tumor antigens in target cells. The purpose of our study was to clarify the cytotoxicity of gd,, T cells expanded ex vivo by the most potent N-BP, zoledronate (ZOL). Especially, we focused on the importance of pretreatment against target cells also with ZOL; 1 m,M ZOL plus IL-2 increased the absolute number of gd,,T cells 298,768 fold for 14 days incubation. The small cell lung cancer and fibrosarcoma cell lines pretreated with 5 m,M ZOL showed a marked increase in sensitivity to lysis by gd,,T cells. While, untreated cell lines were much less sensitive to lysis by gdT cells. Video microscopy clearly demonstrated that gd,,T cells killed target cells pre-treated with ZOL within 3 hr. Pretreatment with 80 m,g/kg ZOL also significantly enhanced the antitumor activity of gd,,T cells in mice xenografted with SBC-5 cells. These findings show that ZOL significantly stimulated the proliferation of gd,,T cells and that gd,,T cells required pre-treatment with ZOL for cytotoxic activity against target cells. © 2005 Wiley-Liss, Inc. [source] Growth Hormone Administration and Exercise Effects on Muscle Fiber Type and Diameter in Moderately Frail Older PeopleJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2001James V. Hennessey MD OBJECTIVE: Reduced muscle mass and strength are characteristic findings of growth hormone deficiency (GHD) and aging. We evaluated measures of muscle strength, muscle fiber type, and cross sectional area in response to treatment with recombinant human growth hormone (rhGH) with or without a structured resistance exercise program in frail older subjects. DESIGN: Placebo-controlled, randomized, double blind trial. SETTING: Outpatient clinical research center at an urban university-affiliated teaching hospital. PARTICIPANTS: Thirty-one consenting older subjects (mean age 71.3 ± 4.5 years) recruited as a subset of a larger project evaluating rhGH and exercise in older people, who underwent 62 quadricep-muscle biopsies. INTERVENTION: Random assignment to a 6-month course of one of four protocols: rhGH administered subcutaneously daily at bedtime, rhGH and a structured resistance exercise program, structured resistance exercise with placebo injections, or placebo injections only. MEASUREMENTS: Muscle biopsy specimens were obtained from the vastus lateralis muscle. Isokinetic dynamometry strength tests were used to monitor individual progress and to adjust the weights used in the exercise program. Serum insulin-like growth factor-I (IGF-I) was measured and body composition was measured using a Hologic QDR 1000W dual X-ray densitometer. RESULTS: The administration of rhGH resulted in significant increase in circulating IGF-I levels in the individuals receiving rhGH treatment. Muscle strength increased significantly in both the rhGH/exercise (+55.6%, P = .0004) as well as the exercise alone (+47.8%, P = .0005) groups. There was a significant increase in the proportion of type 2 fibers between baseline and six months in the combined rhGH treated subjects versus those not receiving rhGH (P = .027). CONCLUSIONS: Our results are encouraging in that they suggest an effect of growth hormone on a specific aging-correlated deficit. IGF-I was increased by administrating rhGH and muscle strength was increased by exercise. The administration of rhGH to frail older individuals in this study resulted in significant changes in the proportions of fiber types. Whether changes in fiber cross-sectional area or absolute number occur with long-term growth hormone administration requires further study. [source] Incidence of Hip and Other Osteoporotic Fractures in Elderly Men and Women: Dubbo Osteoporosis Epidemiology Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2004Kevin P Chang Abstract In this prospective 12-year study in men and women 60 years of age and older, there was a 4,6% per year reduction in the incidence rate of overall osteoporotic fractures, but the study was unable to exclude any change in the hip fracture incidence rate. Approximately one-half of hip fractures occurred before 80 years in men and two-thirds before 85 years in women. The age distribution of hip fractures underlines the need for earlier intervention in osteoporosis. Introduction: Although hip fracture is the major osteoporotic fracture in terms of health outcomes, quality of life, and costs, there is a paucity of long-term data on secular changes in men and women within a defined community. This long-term prospective population-based study over 12 years from 1989 to 2000 specifically examined the age distribution and secular changes in the incidence rates of hip and other osteoporotic fractures in men and women 60 years of age and older in a predominantly white population in Dubbo, Australia. Materials and Methods: Hip and all other clinical fractures were ascertained by reviewing all radiography reports from the two area radiology services, ensuring complete ascertainment of all clinical osteoporotic fractures. Results and Conclusion: Among the 1055 symptomatic atraumatic fractures (after excluding pathological fractures), there was a significant reduction in the overall fracture incidence rate in women (4% per year; p = 0.0003) and men (6% per year; p = 0.0004) over the 12 years. There were 229 hip fractures (175 in women and 54 in men) within 39,357 person-years of observation. The overall rate ± SE of hip fracture was 759 ± 57 per 100,000 person-years in women and 329 ± 45 per 100,000 person-years in men, with an exponential increase with age. With advancing age, the incidence rate of hip fractures in men approached that in women; the female:male ratio fell from 4.5 (95% CI: 1.3,15.7) to 1.5 (0.9,2.5) and 1.9 (1.2,2.8) in the 60,69, 70,79, and 80+ year age groups, respectively. In women, the absolute number of fractures and incidence rate continuously increased with age; however, in men, the absolute number of hip fractures peaked at 80,84 years of age and then decreased. Most importantly, despite the continuing increase with age, almost one-half (48%) of the hip fractures occurred before the age of 80 years in men, and 66% of hip fractures occurred before the age of 85 years in women. The overall hip fracture incidence is comparable with other white (except Sweden) and Asian groups as well as two other Australian studies. This study could not exclude a change in hip fracture incidence rate, even in those 80 years of age and over among whom the incidence of hip fractures was the highest. The incidence data highlight the fact that a large proportion of hip fractures occurs in those under 80 years of age, particularly in men. This age distribution underlines the need for earlier intervention in osteoporosis in women and particularly in men to achieve the most cost-effective outcomes. [source] Reduced reproductive success in small populations of the self-incompatible Primula vulgarisJOURNAL OF ECOLOGY, Issue 1 2004Rein Brys Summary 1Habitat fragmentation and the resulting decline in population size can affect biotic interactions and reproductive success of plant species. We investigated the impact of habitat type, population size, morph type and frequency, plant density, floral display and predation on different reproductive components in 16 populations of the distylous self-incompatible perennial herb, Primula vulgaris , a rare, declining species in Belgium. 2Although habitat type accounted for significant variation in population size, we did not find any relation between habitat type and either reproductive and vegetative characteristics. Population size, however, strongly affected reproductive success, such that plants in small populations produced significantly fewer fruits per plant and seeds per fruit, and therefore fewer seeds per plant. 3No significant difference was found between morph types for any reproductive characteristic, nor an interaction with population size. However, when morph frequency was strongly biased (, 1 : 3), the proportion of flowers setting fruit and the number of seeds per fruit were significantly lower in individuals of the common morph type. 4Within populations, individual plants varied tremendously in size and floral display. Total number of fruits per plant significantly increased with floral display, but the highest fruit set per flower was found at intermediate flower number. 5The proportion of fruit suffering pre-dispersal predation per plant significantly increased with floral display, but this did not offset the potential fitness gains of producing a large display. Furthermore, the absolute number of predated fruits per plant was significantly and positively affected by the interaction of the total number of fruits per plant and the density of the population. [source] The Vanishing Trial: An Examination of Trials and Related Matters in Federal and State CourtsJOURNAL OF EMPIRICAL LEGAL STUDIES, Issue 3 2004Marc Galanter This article traces the decline in the portion of cases that are terminated by trial and the decline in the absolute number of trials in various American judicial fora. The portion of federal civil cases resolved by trial fell from 11.5 percent in 1962 to 1.8 percent in 2002, continuing a long historic decline. More startling was the 60 percent decline in the absolute number of trials since the mid 1980s. The makeup of trials shifted from a predominance of torts to a predominance of civil rights, but trials are declining in every case category. A similar decline in both the percentage and the absolute number of trials is found in federal criminal cases and in bankruptcy cases. The phenomenon is not confined to the federal courts; there are comparable declines of trials, both civil and criminal, in the state courts, where the great majority of trials occur. Plausible causes for this decline include a shift in ideology and practice among litigants, lawyers, and judges. Another manifestation of this shift is the diversion of cases to alternative dispute resolution forums. Within the courts, judges conduct trials at only a fraction of the rate that their predecessors did, but they are more heavily involved in the early stages of cases. Although virtually every other indicator of legal activity is rising, trials are declining not only in relation to cases in the courts but to the size of the population and the size of the economy. The consequences of this decline for the functioning of the legal system and for the larger society remain to be explored. [source] Association between color doppler vascularity index, angiogenesis-related molecules, and clinical outcomes in gastric cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 7 2009Chiung-Nien Chen MD Abstract Purpose This study was conducted to evaluate the correlation between color Doppler vascularity index (CDVI), clinical outcomes and five angiogenesis-related molecules including vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and calreticulin (CRT) in gastric cancer, and to develop an effective model selected from these five molecules to predict patient survival. Patients and Methods CDVI could be obtained preoperatively by transabdominal ultrasound from 30 patients. Enzyme immunoassay was adopted to determine protein level of VEGF and PlGF, and immunohistochemistry was used to detect COX-2, iNOS and CRT expression. Correlation between CDVI and five individual molecules was assessed. Multiple molecules model was developed using classification and regression tree (CART) analysis from five molecules, and was tested for patient survival in another 45 patients. Results CDVI was significantly correlated with patient survival (P,=,0.00907) and absolute number of metastatic lymph nodes (P,=,0.01). There was no significant association between CDVI and any individual molecule. The model, developed by CART consisting of VEGF and PlGF, could differentiate high and low CDVI and survival in testing group (P,=,0.00257). Conclusions CDVI was associated with lymph node metastasis, combined VEGF and PlGF expression status and patient survival in gastric cancer. J. Surg. Oncol. 2009;99:402,408. © 2009 Wiley-Liss, Inc. [source] Landscape context and microenvironment influences on liana communities within treefall gapsJOURNAL OF VEGETATION SCIENCE, Issue 5 2008Agustina Malizia Abstract Questions: How do gap aspect, openness, age and gap density in the surroundings affect diversity and composition of lianas within treefall gaps? Are the variation patterns in liana communities within treefall gaps associated with their climbing mechanisms? Location: Subtropical montane forests in northwestern Argentina. Methods: We used ordination analyses (NMDS) and multiple regressions to describe liana communities (species and climbing groups, stems , 1 cm) in 35 gaps located in a 6-ha plot and to assess relationships with aspect, canopy and subcanopy openness, age and density of recent (three to eight years old) and old (> 8 years old) gaps. Results: Treefall gaps segregated in the ordination diagrams based on their liana species and climbing mechanisms composition: gaps surrounded by a higher density of recent gaps showed higher densities of lianas species using tendrils, spines/hooks and voluble stems. Liana density and richness (independent of stem density) were also positively associated with the density of recent gaps in the surroundings, and negatively associated to gap age. The number of liana species corrected per area was negatively associated to gap aspect and subcanopy openness, and absolute number of liana species was positively associated to gap canopy openness. Conclusions: This study integrates the analysis of different factors influencing liana communities within treefall gaps, and shows that spatial context of gap density (a variable largely neglected in previous studies) is particularly important on lianas composition and diversity, probably by increasing propagule input and the availability of small trellises for support. [source] The significance of small herbivores in structuring annual grasslandJOURNAL OF VEGETATION SCIENCE, Issue 2 2007Halton A. Peters Abstract Question: Herbivores can play a fundamental role in regulating the composition and structure of terrestrial plant communities. Relatively inconspicuous but nevertheless ubiquitous gastropods and small mammals are usually considered to influence grassland communities through distinct modes. 1. Do terrestrial gastropods and small mammals, either alone or in combination, influence plant community composition of an intact annual grassland? 2. Do these herbivores influence the plant size structure of the dominant grass Avena? Location: Jasper Ridge Biological Preserve (37°24' N, 122° 13' W, elevation 150 m) in northern California. Methods: Animal exclosures were used to examine the single and combined influences of these herbivores on annual grassland production, community composition, and plant size structure during the growing season of an intact annual grassland. Results: The removal and exclusion of the herbivores increased the prevalence of grasses relative to legumes and non-legume forbs; increased total production of above-ground plant biomass; and increased mean plant size and exacerbated size hierarchies in populations of Avena. The effect of both gastropods and small mammals, alone and in combination, was characterized by temporal oscillations in the relative dominance of grasses in plots with vs. without herbivores. Conclusions: Both groups of herbivores are important controllers of California annual grassland that exert similar influences on production and composition. While other factors appear to determine the absolute number of individuals in this plant community, selective consumption of grasses by gastropods and small mammals partially offsets the competitive advantages associated with their early germination. [source] T-lymphocyte subsets, thymic size and breastfeeding in infancyPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2 2004Dorthe L. Jeppesen We followed the changes in concentration of T-lymphocyte subsets (CD4+ and CD8+ cells) in peripheral blood and thymus size during infancy. Previous studies have found increased thymus size in breastfed infants. The present study analyzed the association between breastfeeding and the number of CD4+ and CD8+ cells. Two different populations of infants between birth and 1 year of age were examined. Study Group I: infants with a variable duration of breastfeeding. Study Group II: long-term breastfed infants. In both groups a correlation was found between CD8+ cells and the thymic index at 10 months of age. In Group I, infants still breastfed at the 8-month examination had a higher CD8% than formula-fed infants (p = 0.05), and infants breastfed at the 4-month examination had a higher CD4% at 10 months of age (p=,0.03). Group II showed an increase in the absolute number of CD4+ and CD8+ cells from 8 to 10 months of age; and a positive correlation between the number of breastfeedings per day at 8 months of age, and an increase in CD4+ cells from 8 to 10 months of age (p <0.01). In conclusion, a correlation was found between thymus size and CD8+ cells. Breastfeeding might have both a current and long-term immune-modulating effect on the developing cellular immune system. [source] Investigation of molecule chemisorption on Si(001)2 × 1 surfaces by surface reflectance spectroscopiesPHYSICA STATUS SOLIDI (B) BASIC SOLID STATE PHYSICS, Issue 13 2005O. Pluchery Abstract Several examples are given on the investigation of adsorption of atoms and molecules on Si(001)2 × 1 in ultra-high vacuum, by means of two different surface optical spectroscopies, the Surface Differential Reflectance Spectroscopy and the Reflectance Anisotropy Spectroscopy. Hydrogen, water, oxygen, benzene and pyridine adsorptions are presented. Specific spectra are obtained, which are interpreted as a function of the mode of adsorption of the adsorbates. In particular, it is possible to discriminate between adsorption on the dangling bonds of the Si dimers and adsorption inducing a breaking of the dimers. Moreover, quantitative information is obtained from these optical techniques which yields the determination of the absolute number of surface Si atoms involved in the bonding. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Trends in Midlevel Provider Utilization in Emergency Departments from 1997 to 2006ACADEMIC EMERGENCY MEDICINE, Issue 10 2009Michael D. Menchine MD Abstract Objectives:, The objective was to quantify the expansion of midlevel provider (MLP) practice in U.S. emergency departments (EDs) over the past decade. Specifically, we sought to quantify the absolute number of patients seen by MLPs, the annual growth rate of patients seen by MLPs, and the expansion in the proportion of EDs using MLPs. Methods:, Data were analyzed from the ED portion of the 10 most recent years (1997 to 2006) National Hospital Ambulatory Medical Care Survey (NHAMCS), a nationally representative survey of ED visits compiled by the Centers for Disease Control and Prevention (CDC). The main outcomes of interest were the proportion and absolute numbers of ED patients seen by MLPs during the 10-year study period. National estimates derived from sample weights are reported. In addition, a multivariate logistic regression model was created with "seen by midlevel provider" as the dependent variable to determine factors associated with being seen by a MLP. Results:, Between 1997 and 2006, 8.23% (95% confidence interval [CI] = 7.31% to 9.15%) of ED patients were seen by a MLP. The proportion of ED patients seen by MLPs increased from 5.5% (95% CI = 3.8% to 7.1%) in 1997 to 12.7% (95% CI = 10.5% to 14.9%) in 2006 (13% annual growth). This corresponds to an increase in the number of ED patients seen by MLPs from 5.2 million in 1997 to 15.2 million in 2006. The proportion of hospitals using MLPs in the ED increased from 28.3% (95% CI = 22.4% to 34.1%) in 1997 to 77.2% (95% CI = 71.2% to 83.3%) in 2006 (17% annual growth). Slightly over half of MLP cases (54.9%; 95% CI = 49.1% to 60.7%) were also seen by staff physicians. On multivariate regression, younger patient age, non,southern geographic region, and triage acuity were associated with increased MLP use. Conclusions:, The number of ED patients seen by MLPs has increased sharply, from 5.2 million in 1997 (5.5% of all ED cases) to 15.2 million in 2006 (12.7% of all ED cases). Similarly, the proportion of EDs reporting use of MLPs has increased from 28.3% in 1997 to 77.2% in 2006. [source] Association of normal nailfold end row loop numbers with a shorter duration of untreated disease in children with juvenile dermatomyositisARTHRITIS & RHEUMATISM, Issue 5 2010Rochella A. Ostrowski Objective To determine the association of normal numbers of end row loops (ERLs) in nailfold capillaries at the time of diagnosis of juvenile dermatomyositis (DM) with clinical findings in untreated children with the disease and to identify predictors of the development of decreased numbers of ERLs. Methods Clinical and laboratory data from 80 untreated children with juvenile DM were collected. ERL numbers were recorded at the time of diagnosis and at 24 months and 36 months thereafter. The 12 children who had normal ERLs at diagnosis were compared with the remaining 68 children. Outcomes included the duration of untreated disease, the duration of treatment with immunosuppressive medications, family medical history, Disease Activity Score (DAS) for juvenile DM, creatinine phosphokinase level, aldolase level, absolute number of CD3,CD56+/16+ natural killer cells, and von Willebrand factor antigen level. Cross-sectional and longitudinal analyses were performed. Results At diagnosis, children with normal ERLs had a shorter duration of untreated disease (P = 0.03) and a lower skin DAS (P = 0.045). Over time, an increased likelihood of having decreased numbers of ERLs was associated with a longer duration of untreated disease and with a higher skin DAS. Conclusion The presence of a normal number of ERLs in juvenile DM appears to be associated with a shorter duration of symptoms and may be a useful indicator of disease chronicity in the newly diagnosed child. Normal ERLs is also associated with a lower skin DAS. The lack of association between normal ERLs and other variables indicates that normal findings on nailfold capillaroscopy should not be used as justification to delay immunosuppressive therapy in children with typical symptoms of juvenile DM. [source] Elevated CD16 expression by monocytes from patients with tumor necrosis factor receptor,associated periodic syndromeARTHRITIS & RHEUMATISM, Issue 12 2007Ian Todd Objective Tumor necrosis factor receptor,associated periodic syndrome (TRAPS) is an inherited autosomal-dominant autoinflammatory condition caused by mutations in the ectodomain of the 55-kd tumor necrosis factor (TNF) receptor superfamily 1A. Proinflammatory blood monocytes with the phenotype CD14+,CD16+,HLA,DR++ are a major source of TNF, and the number of such monocytes is increased during infection and inflammation. The aim of this study was to investigate whether the expression of circulating CD16+ monocytes is affected in patients with TRAPS. Methods Peripheral blood obtained from patients with TRAPS and healthy control subjects was stained with monoclonal antibodies to detect CD14++,CD16, monocytes and CD14+,CD16+ monocytes, using flow cytometry. Lipopolysaccharide-induced TNF production was measured by intracellular cytokine staining. Activation-induced shedding of CD16 was investigated by treating blood samples with phorbol myristate acetate. Results The level of CD16 expression by CD14+,CD16+ monocytes, but not their absolute number, was significantly elevated in patients with TRAPS, even though the patients were not experiencing clinically overt episodes of autoinflammation at the time of sampling. These findings are similar to those for the C-reactive protein levels and erythrocyte sedimentation rates in the same patients. The enhanced level of CD16 expression by monocytes from patients with TRAPS was not attributable to a defect in activation-induced shedding of CD16. The CD14+,CD16+ monocytes were the predominant source of TNF in both patients and healthy control subjects. Conclusion The level of CD16 expression by monocytes was elevated in patients with TRAPS, as a feature of the underlying constitutive inflammation status. [source] Prognostic value of lymph node ratio in poor prognosis node-positive breast cancer patients in Saudi ArabiaASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 2 2010Ezzeldin M IBRAHIM Abstract Aim: Women in Saudi Arabia develop breast cancer at a young age with high prevalence of poor prognostic features. Because of such features, it is necessary to examine prognostic factors in this population. One such factor is the prognostic role of lymph node ratio (LNR). Methods: We performed retrospective analyses of patients with invasive non-metastatic breast cancer who underwent axillary lymph node dissection and had one or more positive axillary lymph nodes. Results: Two hundred and seventeen patients were considered eligible for the analysis. The median age was 46 years. At a median follow-up of 39.8 months, the median disease-free survival (DFS) was 67.3 months (95% CI, 50.4 to 84.3 months). Neither the classification of patients based on positive lymph node (pN) staging system, nor the absolute number of pN prognosticated DFS. Conversely, age , 35 years at diagnosis, grade 3 tumors and the intermediate (>0.20 to ,0.65) and high (>0.65) LNR categories were the only variables that were independently associated with adverse DFS. Using these variables in a prognostic model allowed the classification of patients into three distinctive risk strata. The overall survival (OS) in this series was 92.5 months (95% CI, 92.1,92.6). Only ER negative tumor adversely influenced OS. Conclusion: Analysis of survival outcome of mostly young patients with early breast cancer identified adverse prognostic variables affecting DFS. If the utility of the derived model including LNR is proven in a larger patient population, it may replace the use of absolute number of positive axillary lymph nodes. [source] Balancing absolute and relative risk reduction in tobacco control policy: the example of antenatal smoking in Victoria, AustraliaAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 4 2010Nathan Grills Abstract Objective: This descriptive epidemiological analysis aims to explore the benefits, risks and policy balance between a whole-of-population and high-risk reduction approach to reducing antenatal smoking prevalence. Methods: Using Victorian hospital antenatal statistics the rate-ratio for smoking in each hypothesised high prevalence group was calculated and combined with the absolute number of births in each high-risk group. The effect on smoking prevalence of whole-of-population reductions and high-risk group reductions was then modelled. Results: In Victoria, there were higher rates of antenatal smoking among single [RR = 4.67 (3.46,4.42)], teenage women [RR (95%CI) = 3.26 (3.00,3.54)] of indigenous ethnicity [RR = 4.39 (3.94, 4.88)] with low income [RR = 4.67 (4.17,5.22)] and low education attainment [RR = 3.89 (3.47,4.36)] who lived in less accessible areas [RR = 2.14 (1.92,2.39)]. However, as each of these high-risk groups represents a relatively small proportion of mothers, most antenatal smokers are aged 25,34, educated, city-based, non-Indigenous and non-impoverished. Conclusions: The majority of Victorian women who smoke in pregnancy do not belong to traditional high-risk groups. Implications: Absolute reductions in smoking prevalence in high-risk groups can potentially be achieved by whole-of-population prevalence reductions, despite a potential continuance in high relative risk among these groups. Conversely, an exclusive focus on smoking reduction in high-risk groups may fail to reduce the whole-of-population antenatal smoking prevalence. [source] Regulatory T cells in atopic dermatitis: epidermal dendritic cell clusters may contribute to their local expansionBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2009A. Szegedi Summary Background, Regulatory T cells (Tregs) have an essential role in tolerance and immune regulation. However, few and controversial data have been published to date on the role and number of these cells in atopic dermatitis (AD). Objectives, To investigate the number of CD4+CD25+FOXP3+ Tregs and interleukin 10-producing T regulatory type 1 (Tr1) cells in patients with AD. Methods, Peripheral blood and skin biopsy samples from atopy patch test (APT)-positive patients with acute- and chronic-phase AD were investigated. Immunohistochemistry was applied to identify CD4+CD25+FOXP3+ Tregs in the skin, while flow cytometry was used to detect CD4+CD25highFOXP3+ Tregs and Tr1 cells in the peripheral blood. Results, In the peripheral blood samples of patients with AD significantly elevated numbers of Tr1 cells were found. Although neither the absolute number nor the percentage of CD4+CD25highFOXP3+ Tregs showed significant alteration in the peripheral blood of patients, increased numbers of FOXP3+ Tregs were detected in skin biopsy specimens. All of the APT-positive skin samples showed epidermal dendritic cell aggregates, morphologically consistent with so-called Langerhans cell microgranulomas, which also contained intermingled FOXP3+ Tregs. Conclusions, Tr1 cell numbers were elevated in the peripheral blood and increased numbers of CD4+CD25highFOXP3+ Tregs were detected in the skin of patients with AD. The epidermal dendritic cell clusters in APT-positive lesional skin showed a close connection to the FOXP3+ Tregs. [source] Follicular miniaturization in female pattern hair loss: clinicopathological correlationsBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2006A.G. Messenger Summary Background, The pathology of female pattern hair loss (FPHL) is characterized by an increase in the proportion of vellus follicles, manifest as a low terminal/vellus ratio. This is conventionally thought to be due to a progressive miniaturization of terminal hair follicles. There is also a prolongation of the latent period of the hair cycle (kenogen) in both male pattern hair loss and FPHL and follicles in kenogen may be difficult to classify histologically. Therefore, a low terminal/vellus ratio could be due to a preferential increase in the number of terminal follicles in kenogen rather than to a true increase in the number of vellus follicles. Objectives, To establish whether there is an increase in the absolute number of vellus follicles during the progression of FPHL, indicating a process of follicular miniaturization. Methods, We studied 42 women complaining of hair loss. The severity of the hair loss was graded clinically on a five-point scale from 1 (no obvious hair loss) to 5 (severe hair loss). Three 4-mm punch biopsies were taken from the frontal scalp of each patient, sectioned horizontally and stained with haematoxylin and eosin. Two levels were studied on each biopsy: through the mid-infundibular region and through the mid-isthmus. The following were counted: total follicles, terminal follicles, vellus follicles, anagen and telogen/catagen follicles. The results from the three biopsies from each subject were averaged and statistical evaluations performed on the mean values. Results, There was a progressive decline in mean total follicle count with increasing grade of hair loss (grade 1, 317 cm,2; grade 5, 243 cm,2) and a more pronounced reduction in terminal follicle counts (grade 1, 263 cm,2; grade 5, 96 cm,2). The absolute number of vellus follicles increased from 33 cm,2 (grade 1) to 71 cm,2 (grade 4), declining to 51 cm,2 at grade 5. The terminal/vellus ratio fell from 12·8 (grade 1) to 2·3 (grade 4) and remained at this level thereafter. The proportion of follicles in telogen increased from 13·7% (grade 1) to 31·4% (grade 5). Conclusions, Our results show that there is an increase in vellus follicle numbers with increasing severity of hair loss in women with FPHL, suggesting that terminal follicles do indeed miniaturize. It is possible that there is also an increase in the number of follicles in a latent stage of telogen but this was difficult to assess from our data. The fall in total follicle counts with stabilizing of the terminal/vellus ratio in severe hair loss suggests that miniaturization does not stop with a vellus follicle but progresses to follicular deletion. [source] | |||||||||||||||||||||||||||||||||||||