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PubMed2006

Cytokines and pregnancy in rheumatic disease.

Cytokines are important mediators involved in the successful outcome of pregnancy. The concept of pregnancy as biased toward a Th2 immune response states that Th1 type cytokines are associated with pregnancy failure and that Th2 cytokines are protective and counteract pregnancy-related disorders. Studies at the level of the maternal-fetal interface, in the maternal circulation and in cells of peripheral blood have shown that the Th2 concept of pregnancy is an oversimplification. Both Th1 and Th2 type cytokines play a role at different stages of pregnancy and are adapted to the localization and function of cells and tissues. The changes of local and systemic cytokine patterns during pregnancy correspond to neuroendocrine changes with hormones as powerful modulators of cytokine expression. Several autoimmune disorders show a modulation of disease activity during and after pregnancy. In rheumatic diseases with a predominance of a Th1 immune response, a shift to a Th2 type immune response during pregnancy has been regarded as beneficial. Studies of pregnant patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have shown a cytokine expression similar to that found in healthy pregnant women. Significant differences were present only for a few cytokines and seemed related to the activity of the underlying disease. Interestingly, a gestational increase of cytokine inhibitors interleukin 1 receptor antagonist (IL-1ra) and soluble tumor necrosis factor receptor (sTNFR) in the circulation corresponded to low disease activity in RA. The influence of hormones and cytokines on autoimmune disease is an issue for further study.

Animals↗
PubMed2005

Soft tissue sarcoma or malignant mesenchymal tumors in the first year of life: experience of the International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor Committee.

PURPOSE: To describe the outcome of infants with a histologically confirmed diagnosis of malignant mesenchymal tumor (MMT) included in the International Society of Paediatric Oncology studies MMT 84 and MMT 89. PATIENTS AND METHODS: One hundred two infants (< or = 12 months old) were included. Twenty-four children were less than 3 months old, and 16 were less than 1 month old. Sixty-four patients had rhabdomyosarcoma (RMS), 26 had undifferentiated sarcoma, and 12 had other histology. Clinical TNM stage was stage I (41%), II (39%), III (6%), and IV (14%). First-line treatment was ifosfamide, vincristine, dactinomycin, whereas the second-line combination consisted of either cisplatin and doxorubicin (in MMT 84) or vincristine, carboplatin, etoposide/teniposide (in MMT 89). Chemotherapy doses were adapted to age. Local therapy was conservative surgery as often as possible. RESULTS: After a median follow-up of 7.8 years (range, 0.1 to 13 years), 5-year overall survival (OS) and event-free survival rates were 66% and 55% for the total study population and 72% and 60% for nonmetastatic patients, respectively. Only two of 13 stage IV patients survived. Sixty-seven percent of newborn infants survived. Infants with alveolar subtype had a poorer survival than those with non-RMS MMT or nonalveolar RMS (5-year OS, 37% v 75% or 82%, respectively; P = .002). When compared with older children with MMT, young age does not seem to be an important prognostic factor. CONCLUSION: OS was satisfactory even when local treatment was not aggressive, although the prognosis was poor for infants with alveolar RMS or metastatic tumors. Chemotherapy toxicity was manageable with appropriate dose modification.

Age Factors↗
PubMed2005

Neonatal screening for sickle cell disorders in Ouagadougou, Burkina Faso: a pilot study.

OBJECTIVES: To determine the incidence of sickle cell disorders (SCDs) and the feasibility of a neonatal screening programme in Ouagadougou. METHODS: During 2000, 2003 and 2004, 2341 cord blood samples obtained in five maternity hospitals in Ouagadougou were screened for SCDs using an isoelectric focusing technique. The feasibility of a neonatal screening programme was evaluated. RESULTS: The incidence of SCD was 1:57; 14 neonates were homozygous for haemoglobin (Hb)S and 27 were compound heterozygotes for HbSC. Thirty-two neonates were homozygous for HbC. The incidence of the HbC trait was 1:6; incidence of the HbS trait was 1:14. A centralized laboratory for neonatal screening of SCDs was established. CONCLUSIONS: SCDs should be considered a major public health problem in Ouagadougou. A neonatal screening programme should be implemented, but to be effective it requires strategies adapted to the local situation.

Anemia, Sickle Cell↗
PubMed2006

Comparative risk assessment of the burden of disease from climate change.

The World Health Organization has developed standardized comparative risk assessment methods for estimating aggregate disease burdens attributable to different risk factors. These have been applied to existing and new models for a range of climate-sensitive diseases in order to estimate the effect of global climate change on current disease burdens and likely proportional changes in the future. The comparative risk assessment approach has been used to assess the health consequences of climate change worldwide, to inform decisions on mitigating greenhouse gas emissions, and in a regional assessment of the Oceania region in the Pacific Ocean to provide more location-specific information relevant to local mitigation and adaptation decisions. The approach places climate change within the same criteria for epidemiologic assessment as other health risks and accounts for the size of the burden of climate-sensitive diseases rather than just proportional change, which highlights the importance of small proportional changes in diseases such as diarrhea and malnutrition that cause a large burden. These exercises help clarify important knowledge gaps such as a relatively poor understanding of the role of nonclimatic factors (socioeconomic and other) that may modify future climatic influences and a lack of empiric evidence and methods for quantifying more complex climate-health relationships, which consequently are often excluded from consideration. These exercises highlight the need for risk assessment frameworks that make the best use of traditional epidemiologic methods and that also fully consider the specific characteristics of climate change. These include the longterm and uncertain nature of the exposure and the effects on multiple physical and biotic systems that have the potential for diverse and widespread effects, including high-impact events.

Climate↗
PubMedDate not supplied

Pathways for continence care: an audit to assess how they are used.

This is a follow-up article to three articles that were published between 2000 and 2001 in the British Journal of Nursing about the development of template pathways for continence care (Bayliss et al, 2000a,b, 2001). It reports on what has happened since the development of these templates. One hundred and forty-four healthcare professionals working in the field of continence care were asked to complete a questionnaire about whether the pathways are being used and what changes have been made to them. The audit found nearly half of the respondents are currently using the pathways and find them an effective method of assessing incontinence and providing equitable quality of care for patients. Many respondents have made changes to the pathways, making them easier to use and adapting them to local practice and the availability of local resources. This was what was anticipated, although the authors noted that variance tracking, which should be the driver for change, had not significantly influenced local pathways. Of those healthcare professionals not using pathways, all said they were still interested in using them, which is particularly encouraging as pathways are promoted in 'Guidelines for Continence Care' (Department of Health, 2000). To provide support to these individuals and encourage the efforts of those already using the pathways, a support group is to be established following a further conference on pathways for continence care later this year. It will be the role of this group to facilitate information sharing on pathway development. As a first step in the dissemination of information, a pack is being produced comprising consolidated versions of the changes to the pathways used in practice all over the country.

Clinical Nursing Research↗
PubMed2006

Wiring the HIV/AIDS system: building interorganizational infrastructure to link people, sites, and networks.

This paper presents a case example of the new "geometry of care" (Rier and Indyk, this volume), by examining selected examples from five facets of a program developed by the lead author and in operation since 1989. This program is designed to understand, build, revise, and maintain the organizational infrastructure with which to link diverse players and sites, and combine these into a web for producing, assessing, and exchanging the information needed to combat HIV/AIDS. Each example demonstrates how opportunities were exploited for developing and linking resources within and between systems of care and prevention. The program began as an iterative and systems approach to improve access of high-risk, hard-to-reach inner city New York populations to HIV/AIDS services, treatment, and research. The approach is also currently being further elaborated and applied in Argentina and India (see Boylan et al., this volume), and is adaptable to other local and global public health challenges (see Indyk & Rier, this volume).

Acquired Immunodeficiency Syndrome↗
PubMed2002

Hypoxic activation of adventitial fibroblasts: role in vascular remodeling.

Substantial experimental evidence supports the idea that the fibroblast may play a significant role in the vascular response to injury, especially under hypoxic conditions. Fibroblasts have the ability to rapidly respond to hypoxic stress and to modulate their function to adapt rapidly to local vascular needs. Fibroblasts appear to be uniquely equipped to proliferate, transdifferentiate, and migrate under hypoxic conditions. Proliferative responses to hypoxia depend on the activation of Galpha(i) and Gq kinase family members, and on the subsequent stimulation of protein kinase C and mitogen-activated protein kinase family members. Extracellular nucleotides (eg, adenosine triphosphate [ATP]) are likely to be increased in the hypoxic adventitial compartment and can act as autocrine/paracrine modifiers of the hypoxia-induced proliferative response. The proliferative effects of ATP appear to be mediated largely through G-protein-coupled P2Y receptors in fetal and neonatal fibroblasts. Hypoxia, acting through Galpha(iota)-coupled pathways, also can directly up-regulate alpha-smooth muscle actin expression in fibroblast subpopulations, suggesting that hypoxia may play a direct role in mediating the "transdifferentiation" of fibroblasts into myofibroblasts in the vessel wall. In addition, chronic hypoxia causes stable (at least in vitro) phenotypic changes in fibroblasts that appear to be associated with changes in the signaling pathways used to elicit proliferation. However, it is also becoming clear that, similar to the heterogeneity described for vascular smooth muscle cells, numerous fibroblast subtypes exist in the vessel wall, and that each may respond in unique ways to hypoxia and other stimuli and thus serve special functions in response to injury. In fact, adventitia may be considered to be compartments in which cells with "stem-cell-like" characteristics reside. Future work is needed to determine more precisely the role of the fibroblast in the wide variety of vascular complications observed in many humans diseases, and in the genes and gene products that confer unique properties to this important vascular cell.

Adult↗
PubMed2007

Review of image-guided radiation therapy.

Image-guided radiation therapy represents a new paradigm in the field of high-precision radiation medicine. A synthesis of recent technological advances in medical imaging and conformal radiation therapy, image-guided radiation therapy represents a further expansion in the recent push for maximizing targeting capabilities with high-intensity radiation dose deposition limited to the true target structures, while minimizing radiation dose deposited in collateral normal tissues. By improving this targeting discrimination, the therapeutic ratio may be enhanced significantly. The principle behind image-guided radiation therapy relies heavily on the acquisition of serial image datasets using a variety of medical imaging platforms, including computed tomography, ultrasound and magnetic resonance imaging. These anatomic and volumetric image datasets are now being augmented through the addition of functional imaging. The current interest in positron-emitted tomography represents a good example of this sort of functional information now being correlated with anatomic localization. As the sophistication of imaging datasets grows, the precise 3D and 4D positions of the target and normal structures become of great relevance, leading to a recent exploration of real- or near-real-time positional replanning of the radiation treatment localization coordinates. This 'adaptive' radiotherapy explicitly recognizes that both tumors and normal tissues change position in time and space during a multiweek course of treatment, and even within a single treatment fraction. As targets and normal tissues change, the attenuation of radiation beams passing through these structures will also change, thus adding an additional level of imprecision in targeting unless these changes are taken into account. All in all, image-guided radiation therapy can be seen as further progress in the development of minimally invasive highly targeted cytotoxic therapies with the goal of substituting remote technologies for direct contact on the part of an operator or surgeon. Although data demonstrating clear-cut superiority of this new high-tech paradigm compared with more conventional radiation treatment approaches are scant, the emergence of preliminary data from several early studies shows that interest in this field is broad based and robust. As outcomes data accumulate, it is very likely that this field will continue to expand greatly. Although at present most of the work is being performed at major academic centers, the enthusiastic adoption of many of the devices and approaches being developed for this field suggest a rapid penetration into the community and the use of the technology by teams of specialists in the fields of radiation medicine, radiation physics and various branches of surgery. A recent survey of practitioners predicted very widespread adoption within the next 10 years.

Humans↗
PubMed2005

Management of healthcare-associated methicillin-resistant Staphylococcus aureus.

Healthcare-associated methicillin-resistant Staphylococcus aureus is a major cause of nosocomial infections worldwide, with significant attributable morbidity and mortality in addition to pronounced healthcare costs. Treatment results with vancomycin--the current recommended antibiotic for serious methicillin-resistant S. aureus infections--have not been impressive. The recent availability of effective antimicrobial agents other than glycopeptides, such as linezolid and daptomycin, as well as the anticipated approval of newer agents with diverse mechanisms of action, has somewhat ameliorated the threat posed by this organism. However, these drugs are expensive, and there is still no overall satisfactory strategy for reducing the incidence of healthcare-associated methicillin-resistant S. aureus in endemic regions. Although early results with the Society for Healthcare Epidemiology of America guidelines give cause for cautious optimism, long-term experience is lacking, and it is likely that these guidelines will have to be adapted according to local conditions and resources before implementation. Trends to keep in mind when considering the problem of healthcare-associated methicillin-resistant S. aureus include the advent of community-associated methicillin-resistant S. aureus, and the propensity of S. aureus to evolve and acquire resistance determinants over time. This was last vividly demonstrated by the handful of vancomycin-resistant S. aureus isolated recently, which had acquired the vancomycin resistance gene from vancomycin-resistant enterococci.

Animals↗
PubMed2001

Human health improvement in Sub-Saharan Africa through integrated management of arthropod transmitted diseases and natural resources.

A concept of an ecosystem approach to human health improvement in Sub-Saharan Africa is presented here. Three factors mainly affect the physical condition of the human body: the abiotic environment, vector-transmitted diseases, and natural resources. Our concept relies on ecological principles embedded in a social context and identifies three sets of subsystems for study and management: human disease subsystems, natural resource subsystems, and decision-support subsystems. To control human diseases and to secure food from resource subsystems including livestock or crops, integrated preventive approaches are preferred over exclusively curative and sectorial approaches. Environmental sustainability - the basis for managing matter and water flows - contributes to a healthy human environment and constitutes the basis for social sustainability. For planning and implementation of the human health improvement scheme, participatory decision-support subsystems adapted to the local conditions need to be designed through institutional arrangements. The applicability of this scheme is demonstrated in urban and rural Ethiopia.

Africa South of the Sahara↗
PubMed2004

Cancer among indigenous people in the Amazon Basin of Ecuador, 1985-2000.

OBJECTIVE: To provide some of the first data on cancer incidence among indigenous people in the Amazon basin of Ecuador, and to compare that incidence with the level found among nonindigenous persons living in that same area. METHODS: From the study area 1 207 cancer cases were reported to the National Cancer Registry over the 1985-2000 period. Frequency and relative risks were calculated for the indigenous residents and for the nonindigenous residents of the area. RESULTS: Cancer of the testes and leukemia were the most common cancer types among indigenous men, and cancer of the cervix uteri was the most common among indigenous women. Indigenous men were at significantly lower risk for cancer of the stomach, skin, prostate, and lymph nodes and for leukemia than were nonindigenous men. Indigenous women were at significantly lower risk for cancer of the stomach, skin, breast, cervix uteri, and lymph nodes than were nonindigenous women. CONCLUSION: Our data from the Ecuadorian Amazon indicate the need to develop appropriate mechanisms to register the indigenous population in the national census as well as in the National Cancer Registry. Also needed are cancer early detection programs, more health education efforts, and stronger health services that are adapted to the local conditions. Future research should focus on factors that may help to explain the different cancer patterns found among indigenous persons and nonindigenous persons.

Adolescent↗
PubMed2006

Flight activity of Melipona asilvai Moure (Hymenoptera: Apidae).

Many stingless bee species are specific to their areas of occurrence. Even when adapted to their local climate and flora conditions, they are subject to modifications in the environment, directly influencing flight activity. The aim of this work is to obtain information about the flight activity of the stingless bee Melipona asilvai Moure, thus contributing to the knowledge of this species. The flow of bees entering and leaving the colony was evaluated, and the type of transported material was identified. This information was correlated with climatic data collected at the time of observations, performed between June 2002 and March 2003. It can be proved that temperature was the factor with the greatest influence on the external activity of this species, showing a significant positive correlation with the entry of bees into the colony and pollen collection. Mud collecting showed a significant positive correlation with a humidity increase. Flight activity began at a temperature of 21.0 degrees C and humidity of 84.5%, peaking at 27.4 degrees C and 60.6% RH, respectively.

Animals↗
PubMed1994

Idiosyncratic drug-induced haematological abnormalities. Incidence, pathogenesis, management and avoidance.

Haematological dyscrasias remain important because they are potentially fatal. Their accurate reporting is required to confirm the cause-effect relationship of suspected adverse drug reactions (ADRs); to estimate their incidence; and, by risk-benefit analysis of such events, to introduce preventive measures to reduce their impact. Limitations within the available data on haematological ADRs are reviewed and some suggestions made for improvement. The drugs most commonly associated with haematological dyscrasias are listed. An understanding of the pathogenesis of haematological dyscrasias is essential for their effective management and these are briefly reviewed. Features common to the management of the different types of haematological dyscrasia include the early involvement of a haematologist and drug information pharmacist and the accurate identification and early withdrawal of any likely offending agent. Guidelines for the management of drug-induced aplastic anaemia, agranulocytosis, thrombocytopenia and haemolytic anaemia are presented and the potential value of granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF; GM-CSF) in the management of agranulocytosis is specifically mentioned. Finally, general principles are discussed whereby serious haematological ADRs might be prevented. These include: the importance of continuing education for drug prescribers; policies on the restricted prescribing of likely offending agents; the use of written instructions for patients; and, the use of haematological monitoring. The guidelines presented in this article should be adapted to meet local circumstances and would prove suitable subjects for audit of their effectiveness.

Adolescent↗
PubMed2006

Exovesicles from human activated dendritic cells fuse with resting dendritic cells, allowing them to present alloantigens.

Dendritic cells (DCs) can release microvesicles, but the latter's numbers, size, and fate are unclear. Fluorescently labeled DCs were visualized by laser-scanning microscopy. Using a Surpass algorithm, we were able to identify and quantify per cell several hundred microvesicles released from the surface of stimulated DCs. We show that most of these microvesicles are not of endocytic origin but result from budding of the plasma membrane, hence their name, exovesicle. Using a double vital staining, we show that exovesicles isolated from activated DCs can fuse with the membrane of resting DCs, thereby allowing them to present alloantigens to lymphocytes. We concluded that, within a few hours from their release, exovesicles may amplify local or distant adaptive immunological response.

Antigen Presentation↗
PubMed1983

Genotype X environment interaction in Hereford cattle: III. Postweaning trait of heifers.

The postweaning performance of heifers from contrasting lines of Hereford cattle was compared simultaneously at Miles City, Montana and at Brooksville, Florida in an experiment designed to evaluate the importance of genotype X environment interactions in beef cattle. During Phase 1 of the study (1964 to 1973), the performance of two unrelated lines, M1 and F6, was compared at the two locations. During Phase 2 (1967 to 1974), two related lines, M1 of Montana origin and F4 derived from M1 by selection in Florida, were compared at each of the two locations. The line X location interaction term was highly significant in either Phase 1, Phase 2 or both for weaning weight, daily gain from weaning to spring, spring yearling weight, daily gain from weaning to fall, fall yearling weight, yearling condition score, conformation score, wither height, body depth, body length, shoulder width, hook width and forecannon circumference. Daily gain of yearlings from spring to fall was the only objective measurement for which the interaction term was nonsignificant in both phases. These results, consistent with the results on performance to weaning age reported previously, indicate the existence of highly significant genotype X environment interactions in beef cattle. The results indicate that genetic adaptation to the local environment is important in beef cattle production and should be considered in designing breeding programs or performance testing procedures and in interregional transfer of breeding stock.

Animals↗
PubMedDate not supplied

3-D components of a biological neural network visualized in computer generated imagery. II. Macular neural network organization.

Computer-assisted reconstructions of small parts of the macular neural network show how the nerve terminals and receptive fields are organized in 3-dimensional space. This biological neural network is anatomically organized for parallel distributed processing of information. Processing appears to be more complex than in computer-based neural networks, because spatiotemporal factors figure into synaptic weighting. Serial reconstruction data show anatomical arrangements which suggest that 1) assemblies of cells analyse and distribute information with inbuilt redundancy, to improve reliability; 2) feedforward/feedback loops provide the capacity for presynaptic modulation of output during processing; 3) constrained randomness in connectivities contributes to adaptability; and 4) local variations in network complexity permit differing analyses of incoming signals to take place simultaneously. The last inference suggests that there may be segregation of information flow to central stations subserving particular functions.

Acoustic Maculae↗
PubMed2002

Cutting edge: negative regulation of immune synapse formation by anchoring lipid raft to cytoskeleton through Cbp-EBP50-ERM assembly.

Ag recognition by T lymphocytes induces immune synapse formation and recruitment of signaling molecules into a lipid raft. Cbp/PAG is a Csk-associated membrane adapter protein exclusively localized in a lipid raft. We identified NHERF/EBP50 as a Cbp-binding molecule, which connects the membrane raft and cytoskeleton by binding to both Cbp through its PDZ domain and ezrin-radixin-moesin through the C terminus. Overexpression of Cbp reduced the mobility of the raft on the cell surface of unstimulated T cells and prevented synapse formation and subsequent T cell activation, whereas a mutant incapable of EBP50 binding restored both synapse formation and activation. These results suggest that anchoring of lipid raft to the cytoskeleton through Cbp-EBP50-ezrin-radixin-moesin assembly regulates membrane dynamism for synapse formation and T cell activation.

Adaptor Proteins, Signal Transducing↗
PubMed2003

The immune response modifier and Toll-like receptor 7 agonist S-27609 selectively induces IL-12 and TNF-alpha production in CD11c+CD11b+CD8- dendritic cells.

IL-12 and TNF-alpha production by dendritic cells (DCs) is a critical step in the initiation of local inflammation and adaptive immune responses. We show in this study that a small molecule immune response modifier that is a Toll-like receptor 7 (TLR7) agonist induces IL-12 and TNF-alpha production from murine CD11c(+)CD11b(+)CD8(-) DCs, a subset not previously known for this activity. Stimulation of these DCs through TLR7 in vivo induces significant cytokine production even 12 h after initial stimulation, as well as migration of the DC into T cell zones of the lymphoid tissue. In contrast, stimulation through TLR4 and TLR9 induced IL-12 production predominantly from CD8(+) DCs, consistent with previously published data. All TLR stimuli induced the increase in surface expression of the activation markers B7-1, B7-2, and class II in both CD8(+) and CD8(-) DCs, demonstrating that CD8(+) DCs do respond to TLR7-mediated stimuli. To date this is the only known stimuli to induce preferential cytokine production from CD8(-) DCs. Given the efficacy of TLR7 agonists as antiviral agents, the data collectively indicate that stimulation of CD8(-) DCs through TLR7 most likely plays a role in the generation of antiviral immune responses.

Aminoquinolines↗