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PubMed2002

The value of synovial fluid assays in the diagnosis of joint disease: a literature survey.

OBJECTIVE: To carry out a critical appraisal of the literature in an attempt to assess the current value of synovial fluid (SF) analysis in the diagnosis of joint disease. METHODS: A literature search was undertaken using the Medline, Biomed, Bids, Pubmed, and Embase electronic databases using the keywords: synovial fluid (SF) analysis, SF crystals, joint sepsis, acute arthritis, and SF cell counts, cytology, biomarkers, and microbiology. RESULTS: Publications fell into three main categories. Firstly, reports assessing the value of the three traditional assays (microbiology, white blood cell counts, and microscopy for pathogenic crystals). For these quality control evidence was found to be sparse, and tests for sensitivity, specificity, and reliability showed worrying variations. These poor standards in SF analysis may be due to lack of inclusion of some tests within routine pathology services. Secondly, claims for the usefulness of "new" assays (cytology and biochemical markers). For cytology, the supporting evidence was mainly anecdotal and there were no reports on specificity, sensitivity, and reliability. Interpretation difficulties are a major hindrance to the clinical use of biochemical assays, which remain primarily research tools. Finally, work on the diagnostic value of SF analysis in general. The appraisal confirmed that SF analysis remains of major diagnostic value in acute arthritis, where septic arthritis or crystal arthropathy is suspected, and in intercritical gout. CONCLUSIONS: Given the importance of SF tests, rationalisation of their use, together with improved quality control, should be immediate priorities. Further investigation is recommended into the contribution of SF inspection and white cell counts to diagnosis, as well as of the specificity and sensitivity of SF microbiological assays, crystal identification, and cytology.

Acute Disease↗

PubMed2003

Global plagues and the Global Fund: Challenges in the fight against HIV, TB and malaria.

BACKGROUND: Although a grossly disproportionate burden of disease from HIV/AIDS, TB and malaria remains in the Global South, these infectious diseases have finally risen to the top of the international agenda in recent years. Ideal strategies for combating these diseases must balance the advantages and disadvantages of 'vertical' disease control programs and 'horizontal' capacity-building approaches. DISCUSSION: The Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) represents an important step forward in the struggle against these pathogens. While its goals are laudable, significant barriers persist. Most significant is the pitiful lack of funds committed by world governments, particularly those of the very G8 countries whose discussions gave rise to the Fund. A drastic scaling up of resources is the first clear requirement for the GFATM to live up to the international community's lofty intentions. A directly related issue is that of maintaining a strong commitment to the treatment of the three diseases along with traditional prevention approaches, with the ensuing debates over providing affordable access to medications in the face of the pharmaceutical industry's vigorous protection of patent rights. SUMMARY: At this early point in the Fund's history, it remains to be seen how these issues will be resolved at the programming level. Nevertheless, it is clear that significant structural changes are required in such domains as global spending priorities, debt relief, trade policy, and corporate responsibility. HIV/AIDS, tuberculosis and malaria are global problems borne of gross socioeconomic inequality, and their solutions require correspondingly geopolitical solutions.

Journal Article↗

PubMed1994

Establishing specific retrovirus-free breeding colonies of macaques: an approach to primary screening and surveillance.

For reasons of occupational safety and animal health, as well as to improve the quality of nonhuman primates used in biomedical research, the establishment and maintenance of specific retrovirus-free breeding colonies of macaques (genus Macaca) are now high priorities. Sensitive and specific screening tests are now available for use in identifying macaques infected with the exogenous simian retroviruses simian immunodeficiency virus (SIV), simian T-lymphotropic virus (STLV), and simian type D retrovirus (SRV/D). A testing algorithm of repeated antibody screening by enzyme immunoassay with confirmatory testing of enzyme immunoassay-reactive sera by Western blot (immunoblot) has proved adequate for identification and exclusion of SIV- and STLV-infected animals in five facilities. In follow-up testing of animals seronegative on primary screening, seroconversions to these two viruses have been rare (0% and < 0.01%, respectively). The testing algorithm for SRV/D must include virus isolation in addition to antibody screening, as some SRV/D-infected animals lack detectable antibody or exhibit a prolonged interval between infection and seroconversion. This parallel testing for SRV/D antibody and virus is critical, especially during primary screening of potential specific pathogen-free stock obtained from external sources. "Indeterminate" immunoblot results, particularly for SRV/D, continue to pose a problem of interpretation. However, preliminary results indicate that newer diagnostic test methods, such as polymerase chain reaction for amplification of proviral DNA, will be useful in resolving SRV/D infection status and will contribute substantially to specific pathogen-free colony development and maintenance.

Algorithms↗

PubMed1994

Plant responses to atmospheric CO2 enrichment with emphasis on roots and the rhizosphere.

Empirical records provide incontestable evidence of global changes: foremost among these changes is the rising concentration of CO(2) in the earth's atmosphere. Plant growth is nearly always stimulated by elevation of CO(2). Photosynthesis increases, more plant biomass accumulates per unit of water consumed, and economic yield is enhanced. The profitable use of supplemental CO(2) over years of greenhouse practice points to the value of CO(2) for plant production. Plant responses to CO(2) are known to interact with other environmental factors, e.g. light, temperature, soil water, and humidity. Important stresses including drought, temperature, salinity, and air pollution have been shown to be ameliorated when CO(2) levels are elevated. In the agricultural context, the growing season has been shortened for some crops with the application of more CO(2); less water use has generally, but not always, been observed and is under further study; experimental studies have shown that economic yield for most crops increases by about 33% for a doubling of ambient CO(2) concentration. However, there are some reports of negligible or negative effects. Plant species respond differently to CO(2) enrichment, therefore, clearly competitive shifts within natural communities could occur. Though of less importance in managed agro-ecosystems, competition between crops and weeds could also be altered. Tissue composition can vary as CO(2) increases (e.g. higher C: N ratios) leading to changes in herbivory, but tests of crop products (consumed by man) from elevated CO(2) experiments have generally not revealed significant differences in their quality. However, any CO(2)-induced change in plant chemical or structural make-up could lead to alterations in the plant's interaction with any number of environmental factors-physicochemical or biological. Host-pathogen relationships, defense against physical stressors, and the capacity to overcome resource shortages could be impacted by rises in CO(2). Root biomass is known to increase but, with few exceptions, detailed studies of root growth and function are lacking. Potential enhancement of root growth could translate into greater rhizodeposition, which, in turn, could lead to shifts in the rhizosphere itself. Some of the direct effects of CO(2) on vegetation have been reasonably well-studied, but for others work has been inadequate. Among these neglected areas are plant roots and the rhizosphere. Therefore, experiments on root and rhizosphere response in plants grown in CO(2)-enriched atmospheres will be reviewed and, where possible, collectively integrated. To this will be added data which have recently been collected by us. Having looked at the available data base, we will offer a series of hypotheses which we consider as priority targets for future research.

Journal Article↗

PubMed2004

[Central issues of prevention of nosocomial infections--status in 2004].

Despite significant progress in our understanding of their pathogenesis, nosocomial infections remain a major problem in hospitals. They may originate from the endogenous flora of the patient as a result of translocation of microorganisms from a physiologically colonized area to an area, where they act as pathogens. Transmission of microorganisms between patients results in exogenous infections. Healthcare workers may serve as transient carriers and vectors or even as reservoir of these infectious agents. Both, exogenous as well as endogenous nosocomial infections are preventable. Based on knowledge of the mode of transmission, the pathogenesis of and risk factors for infection, it is possible to design appropriate preventive strategies, which must be targeted to the type of infection to be prevented and should also be adapted to the local circumstances in a given hospital. Regardless of the type of infection to be prevented, hand disinfection is a standard measure and remains the most important preventive activity. The approach to the prevention of nosocomial infections has to be interdisciplinary and should involve all areas that are affected by any of the proposed measures. Hospital epidemiology plays a central role in coordinating preventive activities and often sets the priorities for prevention based on the available information. Given the growing complexity and the emergence of new nosocomial threats such as SARS, hospital administrators are well advised to invest sufficiently into their department of hospital hygiene and epidemiology in order to be ready for all the problems that will need to be tackled in the future.

Bacterial Infections↗

PubMed2003

Analysis of structure and function of putative surface-exposed proteins encoded in the Streptococcus pneumoniae genome: a bioinformatics-based approach to vaccine and drug design.

Streptococcus pneumoniae is the most common cause of fatal community-acquired pneumonia, middle ear infection, and meningitis. The prevention and treatment of this infection have become a top priority for the medical-scientific community. The present polysaccharide-based vaccine used to immunize susceptible hosts is only approximately 60% effective and is ineffective in children younger than 2 years of age. The new conjugate vaccine, based on the engineered diphtheria toxin coupled to polysaccharide antigens. is approved only for use in children under 2 years of age to treat invasive disease. While penicillin is the drug of choice to treat infections secondary to S. pneumoniae, increasing numbers of bacterial strains are resistant to penicillin as well as to broad spectrum antibiotics such as vancomycin. Thus, there is a need to identify new strategies to prevent and treat diseases caused by to S. pneumoniae. In this article, we summarize the utilization of the recently available S. pneumoniae genomic information in order to identify and characterize novel proteins likely located on the surface of this Gram-positive pathogenic bacterium. Because only a limited number of surface proteins of S. pneumoniae have been characterized to date, this information provides new insights into the pathogenesis of this organism as well as highlights possible avenues for its treatment and/or prevention in the future. The review is divided into two sections. First, we brietly summarize current information about known surface-exposed proteins of S. pneumoniae. This is followed by the illustration of procedures for the identification of new putative surface-exposed proteins. These have signal peptides required for their extra-cytoplasmic transport and/or additional signature sequences. Some of these will be S. pneumoniae virulence factors. The signature sequences we have chosen are those leading to protein binding to choline present on the bacterial surface, attachment to peptidoglycan of the cell wall, or anchoring to lipids of the cytoplasmic membrane. All these signatures are indicative of binding of proteins to the surface of this organism. Secondly, we illustrate the application of bioinformatics and modeling tools to these selected proteins in order to provide information about their likely functions and preliminary three-dimensional structure models. The focal point of the analysis of these proteins, their sequences, and structures is the evaluation of their antigenic properties and possible roles in pathogenicity. The information obtained from the genome analysis will be instrumental in the development of a more effective prophylactic and/or therapeutic agents to prevent and to treat infections due to S. pneumoniae.

Amino Acid Sequence↗

PubMed2005

Military importance of diarrhea: lessons from the Middle East.

PURPOSE OF REVIEW: Historically, diarrhea has been one of the most important diseases encountered during military operations. With more than 140,000 US military personnel currently deployed to the Middle East in support of the global war on terror, it is important for health care providers and planners to be aware of the incidence and potential impact of diarrheal disease in that region. RECENT FINDINGS: Recently published data from mid-deployment surveys assessing the incidence and clinical impact of diarrhea on troops deployed to Iraq and Afghanistan have been updated and presented along with a review of the recent literature concerning diarrheal pathogens of military concern in the Middle East. Of 4348 volunteers, 76% reported at least one diarrhea episode during their deployment and more than half reported multiple episodes. In 45% of subjects, diarrhea resulted in decreased job performance for a median of 3 days. Diarrhea resulted in 62% of subjects seeking medical care at least once, and 31% required intravenous rehydration. In 17% of subjects, diarrhea resulted in confinement to bed for a median of 2 days, causing an estimated 3.7 days (Poisson 95% CI, 3.4 to 4.0 days) of complete work loss per 100 person-months. SUMMARY: Despite modern preventive medicine efforts, diarrhea rates remain high, and the impact of illness remains a threat to military efficiency. Novel enteric disease research programs designed to decrease the impact of diarrhea on the military mission are needed. The development of enteric vaccines and appropriate treatment regimens remain a top priority.

Absenteeism↗

PubMedDate not supplied

The role of Haemophilus influenzae in the pathogenesis of pneumonia.

Haemophilus influenzae, one of the bacteria comprising the commensal flora of the human upper respiratory tract, is also pathogenic and causes both localized and invasive (septicemic) infections. The major focus of attention and research has been on infections caused by serotype b organisms, which cause several life-threatening illnesses in children, including meningitis and acute respiratory infection (ARI; e.g., epiglottitis, pneumonia). Type b polysaccharide-protein conjugate vaccines are at an advanced stage of development and implementation; however, these vaccines will not protect against noncapsulated (nontypable) strains of H. influenzae or strains expressing capsular polysaccharides other than serotype b, strains which cause a substantial proportion of ARI (especially pneumonia) among infants, particularly in developing countries. The magnitude of this problem, which contributes to many thousands-perhaps millions-of deaths each year, emphasizes the need for research on the epidemiology, pathogenesis, virulence factors, immune mechanisms, and forms of treatment relevant to ARI caused by H. influenzae in infants and implies that such studies should be given a high priority.

Carrier State↗

PubMed2000

Evolution of the management of depression in Spain from the psychiatrist's perspective. A comparative analysis: 1997 vs 1982.

The main problem of depression is not only the high prevalence of the disorder but also its serious consequences on the patient's quality of life and the associated social costs in terms of health care resource utilization and productivity losses. In recent years, there has been a considerable improvement in the knowledge of depression from the pathogenic, clinical and therapeutic perspectives. The present study analyzes whether such advances are reflected in a positive evolution of the treatment of depression in Spain. To this effect we have contrasted the results of two socio-sanitary studies published in this country: the White Book editions of 1982 and 1997 (WB82 and WB97, respectively). From the methodological perspective, the physician selection criteria employed were very uniform (structured questionnaires delivered to 128 (WB82) and 300 (WB97) randomly selected psychiatrists). The origin of patients consulting for specialized care has varied over this 15-year period. In effect, WB82 patients were essentially referred by friends (87.5%) and from the primary care setting (44.5%), whereas in the WB97 study referral from primary care predominated (50.1%), followed by the patient's personal decision (24.8%). In turn, 40.7% and 51.7% of the psychiatrists in WB97 respectively considered the diagnostic and therapeutic means available in primary care to be insufficient. The priorities for improving patient quality of life, as reflected by both editions of the study, were the training of primary care physicians and the adequate provision of means in the mental health care centers. On the other hand, fewer problems for establishing a correct diagnosis were referred in the 1997 edition of the study (28.7%) than in 1982 (48.4%). In this sense, the main problem reported in WB82 was the lack of specialized training, whereas the masking of depression by some other disease process or symptoms was the main problem in WB97 (67.6% vs 21.1% according to WB82). The main symptoms upon which the diagnosis of depression are based do not seem to have evolved much in the past 15 years. The most frequently cited manifestations were a worsening of mood, loss of interest and leisure capacity, sleep alterations and diminished vitality. A comparative analysis of the therapeutic resources used was not possible, for prior to 1982 the only drugs available to physicians were the classical tricyclic agents and some MAO inhibitors; the selective serotonin reuptake inhibitors (SSRIs) - possibly the greatest advance in the treatment of depression in these 15 years - had not yet been introduced. Nevertheless, it should be pointed out that 98% of the psychiatrists consulted in WB97 considered pharmacologic treatment to be the most widely adopted form of management once depression has been diagnosed.

Antidepressive Agents↗

PubMed1997

Epidemiology and control of egg-associated Salmonella enteritidis in the United States of America.

The isolation rate for Salmonella enterica serotype Enteritidis (SE) in humans in the United States of America (USA) increased from 1,207 sporadic isolates identified in 1976 (0.6 isolates/100,000 population) to 10,201 identified in 1995 (4.0/100,000 population). The proportion of reported Salmonella isolates which were SE increased from 5% to 25% during the same time period. In 1990, 1994, and 1995, SE was the most commonly reported reported Salmonella serotype in the USA. Much of this increase has been associated with the consumption of contaminated shell eggs. An examination of the results of a United States Department of Agriculture (USDA) survey of spent hens at slaughter and unpasteurised liquid egg at breaker plants (liquid egg processors) in 1991 and 1995 reveals an increase in the prevalence of SE isolates overall and in most regions of the USA. SE phage type 4 (pt 4), the predominant SE phage type in other parts of the world, has emerged in the egg industry in the western USA concurrent with a sharp increase in the number of sporadic human SE pt 4 isolates in California and Utah. Research on the molecular structure and virulence of SE pt 4 isolates from the USA as compared with isolates from other parts of the world (human and poultry) should be a priority. A comparison of DNA from pt 4 isolates from the USA and Europe may provide information about the potential threat to public health and poultry in the USA from this phage type. Some regional success in the reduction of human illness as a result of SE control efforts is apparent. The Pennsylvania Egg Quality Assurance Program has shown progress in reducing SE infection in participating flocks. At a national level, however, neither the incidence of human illness due to SE nor the prevalence of SE in flocks and unpasteurised liquid eggs have decreased significantly, despite the implementation of the USDA 'trace back' regulation from 1990 to 1995, and intensified efforts to educate food handlers and to enforce safe food handling practices. More effort is needed to control SE at every stage of the egg continuum, from production through to consumption. A risk-reduction approach, with barriers to the introduction and multiplication of the pathogen throughout the farm-to-table continuum, is the most practical method for reducing human illness from SE in shell eggs at present. An effective long-term solution will require interdisciplinary efforts involving government, industry, consumers, and academics. Interventions should be developed and evaluated in compliance with the potential for reducing the risk to human health and cost-effectiveness.

Animal Husbandry↗

PubMed1998

International collective action in health: objectives, functions, and rationale.

To improve the performance of international health organisations, their essential functions must be agreed. This paper develops a framework to discuss these essential functions. Two groups are identified: core functions and supportive functions. Core functions transcend the sovereignty of any one nation state, and include promotion of international public goods (eg, research and development), and surveillance and control of international externalities (eg, environmental risks and spread of pathogens). Supportive functions deal with problems that take place within individual countries, but which may justify collective action at international level owing to shortcomings in national health systems-such as helping the dispossessed (eg, victims of human rights violations) and technical cooperation and development financing. Core functions serve all countries, whereas supportive functions assist countries with greater needs. Focus on essential functions appropriate to their mandate will better prepare international health organisations to define their roles, eg for WHO to focus on core functions and for the World Bank to focus on supportive ones.

Global Health↗

PubMed2026

CRISPR-Cas and Infectious Diseases: A Decade of Translational Advances in Molecular Biotechnology.

CRISPR-Cas systems have emerged as a versatile tool for diagnosing, treating, and preventing infectious diseases. This review highlights translational advancements in CRISPR-Cas-based applications, concentrating on the past decades in diagnostics, therapeutic genome editing, and vaccine development. The article highlights key platforms like DETECTR and SHERLOCK, which enable rapid, sensitive pathogen detection, and explores CRISPR-Cas9 systems in therapeutic strategies for directly targeting viral genomes and combating antimicrobial resistance. It also examines the role of CRISPR-Cas9 in engineering live-attenuated and personalized neoantigen vaccines. Principal findings demonstrate a clear progression from experimental proof-of-concept to preclinical applications primarily in CRISPR-based diagnostics and the engineering of live-attenuated vaccine candidates, whereas translation in CRISPR-based therapeutics and personalized neoantigen vaccines for infectious diseases remains at earlier, more exploratory stages. CRISPR-based diagnostics have progressed further toward clinical evaluation than therapeutics due to delivery and safety constraints, while personalized neoantigen vaccines are included mainly as an emerging, comparative concept for infectious diseases rather than a mature application. This review uniquely integrates CRISPR-based diagnostics, therapeutics, and vaccine development within a single infectious disease framework, critically assesses their current maturity, and systematically highlights technical, regulatory, and ethical barriers alongside realistic future priorities. The review concludes that while CRISPR-Cas holds transformative potential for infectious disease management, significant challenges in delivery efficiency, off-target effects, and ethical regulation must be addressed to ensure safe and equitable clinical translation.

Humans↗

PubMed1996

The role of epidemiology and surveillance systems in the control of sexually transmitted diseases.

Surveillance and epidemiological studies are essential components of effective control programmes for sexually transmitted diseases. While other forms of basic biomedical research may add to our understanding of why an exposure or behaviour causes or prevents disease, only epidemiology allows the quantification of the magnitude of the exposure-disease relationship in humans. It is this measure of the association between risk and disease that is needed to inform rational policy on altering risk through intervention. Surveillance data are used both to determine the need for public health action and to assess the effectiveness of programmes: they are required for the setting of priorities, for planning and resource allocation, for the definition of population subgroups and risky behaviours for targeted interventions, for the development of disease prevention programmes, and for the evaluation of interventions. Data from surveillance systems and epidemiological studies can also inform diagnostic and therapeutic practice, and indicate areas for further research. Over the last 20 years chlamydia infections and viral agents have emerged as the major cause of STD in developed countries, and with this change in the aetiological mix of STD cases the focus of prevention and control of STDs has shifted from treatment and partner notification towards health education. In developing countries there is an urgent need for appropriate surveillance infrastructures, particularly now that there is evidence that STD control programmes, informed by surveillance data, can reduce HIV transmission at the population level. The importance of surveillance and epidemiology in the control of STDs is set to increase in the face of the changing pattern of sexually transmitted pathogens. The challenge to clinicians and epidemiologists is to work together in developing systems that will inform new approaches to control and prevention.

Developing Countries↗

PubMed2005

Phase I safety study of Praneem polyherbal vaginal tablet use among HIV-uninfected women in Pune, India.

Praneem polyherbal formulations containing purified extracts of Azadirachta indica (neem tree) have shown activity against HIV and sexually transmitted disease pathogens in studies in vitro. The product also has contraceptive properties. This has prompted its development as a possible microbicide. We evaluated the safety of Praneem polyherbal tablet use among HIV-uninfected women. Twenty eligible women were enrolled in a Phase I open-label study requiring 14 days of consecutive intravaginal use of Praneem polyherbal tablets. Nine (45%) participants experienced 17 episodes of genital irritation. Transient genital itching was reported by eight (40%) participants, burning micturation by two (10%) and lower abdominal pain, genital burning and intermenstrual spotting by one (5%) each. On colposcopy, petechial haemorrhage was observed in two participants, one on day 7 and the other on day 14, and both were resolved without any treatment. There were no serious adverse events. Praneem polyherbal tablets were found to be safe for once daily intravaginal use for 14 consecutive days in sexually active HIV-uninfected women and a Phase II study may be taken up as a priority.

Administration, Intravaginal↗

PubMed1988

Human retroviruses.

After many unsuccessful years of searching, the first pathogenic human retrovirus, the human T-cell leukaemia lymphoma virus (HTLV-I), was reported as recently as 1980 and since that time has been causally linked to the adult T-cell leukaemia lymphoma syndrome. A second HTLV (HTLV-II) isolated shortly afterwards is less clearly linked to some leukaemic and chronic lymphoid malignancies. The second major family of human retroviruses are the human immunodeficiency viruses (HIV) the first group of isolates (HIV-I) of which cause the acquired deficiency syndrome (AIDS). A second group of these viruses (HIV-II), have recently been identified in West Africa. They appear to be less clearly associated with disease and more similar in molecular structure to the Simian immunodeficiency viruses. AIDS has now become a major global pandemic, and vaccine and therapeutic strategies are urgently being investigated in an effort to control the disease. Unfortunately, current results are not very encouraging. In the meantime, preventative and educational measures are of utmost priority in order to prevent further spread. It is not unlikely that new human retroviruses will be discovered over the next few years.

Deltaretrovirus Infections↗

PubMed2005

Current concepts in the evaluation, diagnosis and management of acute infectious diarrhea.

Despite recent advances in our understanding of the pathogenesis of enteric diseases, acute infectious diarrhea remains a major cause of morbidity and mortality worldwide. Infection is the most common cause of acute diarrhea. Some causes of infectious diarrhea also result in serious long-term sequelae such as hemolytic uremic syndrome, Guillain-Barré syndrome and malnutrition. A better understanding of bacterial pathogenesis has grown increasingly important because of the emergence of new pathogens and the growing problems of resistance among enteric pathogens and other enteric flora. Non-antimicrobial approaches to therapy have become increasingly important with the emergence of serious antimicrobial resistance, such as vancomycin-resistant enterococcal colonization of the gastrointestinal tract. Finally, new understanding of how intestinal bacteria cause disease is revealing that enteric infections might trigger damage to epithelial cells or the intestinal barrier, or disrupt intestinal barrier and absorptive function (without necessarily causing overt diarrhea); thus, enteric infections might be far more important as emerging causes of malnutrition than has been previously appreciated. Therefore, diarrhea is both a cause and an effect of malnutrition. Treatment in most cases of bacterial and viral diseases consists of correcting fluid loss and electrolyte imbalance by oral or parenteral rehydration. Prevention of enteric illness by virtue of improved hygiene and provision of sanitation and water treatment is impractical in most developing countries, where morbidity and mortality rates are highest. For this reason, development of vaccines against the most important gastrointestinal infections remains a high priority.

Acute Disease↗

PubMed2005

Gene expression signatures in neutrophils exposed to glucocorticoids: a new paradigm to help explain "neutrophil dysfunction" in parturient dairy cows.

Neutrophils are the first line of immunity against most pathogens that infect cattle. These normally short-lived white blood cells develop from myeloid-lineage cells in bone marrow. Upon maturation, bone marrow neutrophils are released into the circulation where they marginate on inflamed blood vessel endothelial cells and migrate through them into the area of infection. Once migrated, neutrophils do not reenter the circulation, but rather, perform their bactericidal functions and die by apoptosis in the tissue. The cytokine and hormonal milieu of the blood and extracellular tissue fluid can influence neutrophil development and immunity-related activities, but the molecular basis of these phenotypic changes and physiological benefits or drawbacks of them are poorly understood. In the current paper, we review new gene expression information that resulted from two of our functional genomics studies designed to evaluate effects of glucocorticoid hormones on bovine neutrophils. This work provides one model to describe complex changes that occur in neutrophils as the cells respond to glucocorticoids, which might act to alter the cells' functional priorities and tip the delicate balance between health and disease during stress, including at parturition. A bovine immunobiology microarray and real time RT-PCR were used to study blood neutrophils collected during the natural surge of endogenous glucocorticoid (cortisol) in parturient dairy cows and bone marrow neutrophils collected from glucocorticoid (dexamethasone)-treated dairy steers. The gene expression signatures we observed led us to perform additional phenotyping of the neutrophils and correlation analyses, which together painted a picture suggesting that glucocorticoids have key roles in modulating neutrophil development, life span, and tissue defense functions during parturition and hormone therapy. Based on these observations, we postulate that glucocorticoids orchestrate adaptive changes in the entire neutrophil system that support increased cell numbers and longevity in blood and heightened remodeling activity in tissues, while at the same time decreasing some important antimicrobial defense activities of the cells. Thus, our functional genomics studies have enabled us to elucidate multiple consequences of neutrophil exposure to glucocorticoids, highlighting a probable role for this interaction in the induction of parturition and partly explaining why some parturient dairy cows may experience heightened incidence and severity of inflammatory diseases like mastitis.

Animals↗

PubMed1998

Blood-borne virus-related discrimination in dental services.

While the risk of infection through occupational exposure to blood-borne viruses is a major concern of dental health care workers, the National HIV/AIDS Strategy and many health, AIDS and discrimination-related agencies have identified discrimination related to HIV/AIDS as a priority area for action. In 1995 the Commonwealth Department of Health and Family Services selected the School of Medical Education at the University of New South Wales to conduct a national project to reduce discrimination related to blood-borne viruses within dental services (Godwin, Meihubers & Rotem 1997). This paper provides an overview of the study and its major findings. The study focused on quality of care issues which may cause or manifest discrimination. Key stakeholders were invited to review policies, procedures, organisational arrangements and other systemic issues which influence the quality of oral health services to populations within selected geographical regions.

Blood-Borne Pathogens↗