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Biomedical subjects

Andrea T Borchers

Publications and source records attributed to Andrea T Borchers.

At least 19 recordsLinked to original sources
PubMed2006

Ankylosing spondylitis: a contemporary perspective on diagnosis and treatment.

OBJECTIVES: In recent years, great progress has been made in the development of diagnostic tools, therapeutic approaches, and validated outcome measures in the understanding of the pathogenesis of ankylosing spondylitis (AS). The purpose of this review was to summarize these developments. METHODS: We performed a PubMed search for the period 1978 to 2005, using the keyword, "ankylosing spondylitis," resulting in a total of 4878 publications, including 778 reviews. Articles were then selected based on their discussion of recent diagnostic tools and new treatment approaches in the pathogenesis of AS, leading to a final total of 104 articles. RESULTS: In recent years, there have been 2 major developments in the management of AS that make earlier diagnosis possible and offer the hope of alleviating pain and preventing structural changes that result in loss of function. These developments include the use of magnetic resonance imaging to visualize the inflammatory changes in the sacroiliac joint and the axial spine, and the demonstration that tumor necrosis factor blocking agents are highly efficacious in reducing spinal inflammation and possibly in slowing radiographic progression. CONCLUSIONS: There have been major advances in both the diagnostic tools and the therapeutic regimens available for patients with AS.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Airborne environmental injuries and human health.

The concept that the environment in which we live can have detrimental effects on our health has existed for centuries. Obvious examples of substances that can cause human diseases include infectious agents, poisons, chemicals and other noxious agents, drugs, and physical stimuli such as bright lights and loud sounds. Some less obvious agents can include allergens, nontangible agents such as colorless, odorless gases and aerosolized toxins. In recent decades, humans have developed various new materials and compounds. Additionally, we are now producing known compounds, and even naturally occurring substances, in vastly increased amounts. Many of these substances are generally believed to threaten the health of our environment. However, there is also a considerable amount of hype and exaggeration regarding some of these agents (e.g., mold) that is unsubstantiated. This article extensively reviews the data on a large number of airborne-related illnesses and attempted to place scientific reality in the context of clinical medicine.

Air Pollutants↗
PubMed2005

Juvenile idiopathic arthritis.

One of the most enigmatic problems in rheumatology has been juvenile idiopathic arthritis (JIA). Firstly, the classification has often depended on clinical features that have variations between patients. Secondly, there are different classification schemes in usage and there are few objective serologic tests that help to resolve the differences between the criteria sets. Thirdly, only recently have significant advances been made in understanding the immunology and immunopathology of JIA and, in particular, new treatment options. In this review, we will define the historical basis of JIA and emphasize not only the clinical features, but also the immunological characteristics, the pathogenesis, and treatment options. We will also discuss, in particular, quality of life, psychosocial functioning, socioeconomic outcomes and the difficult area of mortality. Finally, this review will attempt to bridge genetic observations with clinical presentation. JIA represents a relatively common syndrome of pediatric onset rheumatologic disease and a better understanding of the clinical definition, the relationship to autoimmunity, and novel treatments with biologic agents are critical for improved patient care.

Adolescent↗
PubMed2005

NOD mice and autoimmunity.

The NOD mouse has been an important model of type 1 diabetes and autoimmune diseases for over 20 years. Experimental and genetic manipulations of the NOD mouse have demonstrated a broad susceptibility to multiple autoimmune syndromes. This predisposition to autoimmunity is due to defects in both central and peripheral tolerance. The defect of central tolerance is likely secondary to improper negative selection mediated by the unique MHC Class II molecule, I-A(g7) as well as intrinsic T cell signaling defects. The genetic basis for impaired peripheral tolerance is controlled by over 20 susceptibility loci termed insulin-dependent diabetes (idd) loci. The maintenance of peripheral tolerance is impaired by alterations in T cell signaling and apoptosis. In addition, insufficient co-stimulation from accessory cells, and defective regulatory T cells, may promote the production of autoreactive T cells.

Animals↗
PubMed2005

Neuropsychiatric features of systemic lupus erythematosus.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious and well known complication of systemic lupus erythematosus that remains a significant source of morbidity and mortality. Fortunately, advances in neuroimaging techniques and cognitive testing have improved the diagnosis of this disease and allowed earlier and more successful therapeutic intervention. Further, the association of NPSLE with the anti-phospholipid syndrome, other autoantibodies and inflammatory cytokines have also provided clues to the diagnosis and pathophysiology. Treatment of NPSLE is largely symptom based with outcome based on appropriate diagnosis.

Humans↗
PubMed2005

Transforming growth factor beta (TGF-beta) and autoimmunity.

TGF-beta1 deficient mice develop multifocal inflammatory autoimmune disease and serve as a valuable animal model of autoimmunity. Transgenic expression of a dominant negative form of TGF-beta receptor type II in T cells have enabled the study of cell lineage specific effects of TGF-beta providing clues to the potential etiology of autoimmunity. These studies suggest that TGF-beta deficiency may induce autoimmune disease by influencing a number of immunological phenomena including lymphocyte activation and differentiation, cell adhesion molecule expression, regulatory T cell function, the expression of MHC molecules and cytokines, and cell apoptosis. The spectrum of effects appears to be significant in mucosal immunity and may contribute to the pathogenesis of inflammatory bowel disease.

Animals↗
PubMed2005

Hope for the hygiene hypothesis: when the dirt hits the fan.

The hygiene hypothesis was developed in response to data suggesting that the increase in allergic diseases as well as asthma was secondary to a reduced exposure to infectious stimuli. Indeed, the epidemiologic changes, resulting in an increase in atopic disease, have been impressive and intriguing. Furthermore, although there clearly is a genetic component to atopic diseases, genetics cannot account for a marked increase in the incidence and prevalence of allergic manifestations within a few generations. Thus, environmental factors have been suggested as responsible for the changing prevalence. There are two--not mutually exclusive--possibilities, namely, that substances that promote atopy have been added to the environment or that factors that provided protection from allergic disease were lost from the environment. Both outdoor and indoor pollution, along with a long list of other environmental factors, have been proposed. It is of interest that in many developed countries, certain types of pollution have decreased, whereas the prevalence of atopic disease has increased. In this review, we have explored a detailed analysis of a large number of studies that have focused on this issue and suggest that, although the hygiene hypothesis has merit, the stimuli responsible for the new epidemiology remain enigmatic.

Asthma↗
PubMed2004

The diagnosis and management of anaphylaxis.

Anaphylaxis is amongst the most frightening reactions that any physician will face. What often separates life and death is the acute management, including the proper use of epinephrine. In this review, the differential diagnosis and management plan are outlined.

Adrenergic Agonists↗
PubMed2004

Surviving the butterfly and the wolf: mortality trends in systemic lupus erythematosus.

OBJECTIVE: To address changes in survival of patients with systemic lupus erythematosus (SLE) and to compare mortality statistics with associated disease specific as well as comorbid conditions. METHODS: Review of the international literature on survival of patients with SLE. RESULTS: During the first half of the 20th century, SLE was considered a rapidly progressive and almost invariably fatal disease. Since the 1950s, the estimated 5-year survival of SLE patients in developed countries rose from <50% to >95% and similar increases were seen in 10-year survival. Mortality rates of SLE patients, however, remain approximately 3 times that of an age- and sex-matched population in most studies, indicating that death still occurs prematurely in a substantial portion of patients, albeit later in the disease course. This improved prognosis does not appear to have been shared equally by all racial/ethnic groups. This appears to be attributable more to socioeconomic and sociocultural factors than to true differences in disease manifestations. Along with the increased survival of SLE patients, there has been a change in the causes of death. Most notably, there has been a dramatic increase in the proportionate mortality from vascular disease, particularly accelerated atherosclerosis. Both disease and therapeutic modalities, in particular corticosteroids, appear to contribute to the high prevalence of coronary artery disease (CAD). CONCLUSIONS: Much progress has been made in improving the survival of SLE, but there is need for further improvement. Aggressive treatment of risk factors for CAD is advisable, but it remains to be assessed to what extent such interventions can further reduce mortality.

Arteriosclerosis↗
PubMed2004

The use of methotrexate in rheumatoid arthritis.

OBJECTIVE: To address the long-term efficacy and toxicity issues related to methotrexate (MTX) and compare it with other disease-modifying antirheumatic drugs (DMARDs). METHODS: Review of the international literature on the clinical use of MTX in rheumatoid arthritis (RA) disease. RESULTS: MTX has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies, particularly because of its considerably longer median drug survival. The toxicity profile of MTX is well established and includes serious and sometimes fatal liver disease, pneumonitis, and cytopenias. Hence, regular and careful monitoring of patients taking MTX is essential, particularly when MTX is combined with other DMARDs. Folate supplementation can reduce some of the most common side effects of MTX, but it has not yet been established whether this translates into a reduced risk of serious disease. Another potential approach to reducing the toxicity of MTX is therapeutic drug monitoring and dose individualization. However, correlations between pharmacokinetics and clinical response have been addressed in only a few studies and with conflicting results. CONCLUSIONS: MTX is an effective DMARD with a relatively safe profile compared with other therapies. Folate supplementation can significantly reduce the risk of MTX toxicity. Finally, it is essential that patients be monitored carefully to reduce the potential serious toxicities of MTX.

Adult↗
PubMed2004

The asymmetry of existence: do we owe our existence to cold dark matter and the weak force?

A common theme throughout biology is homochirality, including its origin and especially implications. Homochirality has also intrigued scientists because of the hypothesis that life, as it currently exists, could not have occurred without it. In this review, we discuss several hypotheses regarding homochirality and their linkage to processes that range from subatomic in scale to processes that help define the structure of the universe. More importantly, this exploration begins with the knowledge that humans inhabit the universe in which there is an excess of normal matter over antimatter. It is a universe characterized by homochirality but is nonetheless contained in what is most easily described as a 3+1 dimensional spacetime wherein most laws of physics are invariant under spacetime transformations. This restriction on spacetime poses significant constraints on the processes that can be invoked to explain homochirality. However, in dealing with such restraints, including the total mass contained in the universe, the concepts of cold dark matter and dark energy can be incorporated into cosmological models with resultant behaviors and predictions very much in accord with the findings of the cosmic background surveys. Indeed, the introduction of cold dark matter and dark energy to solve problems relating to the mass found in the universe may provide a means for generating the needed asymmetry to allow homochirality to arise.

Astronomy↗
PubMed2004

Mushrooms, tumors, and immunity: an update.

There is significant interest in the use of mushrooms and/or mushroom extracts as dietary supplements based on theories that they enhance immune function and promote health. To some extent, select mushrooms have been shown to have stimulatory action on immune responsiveness, particularly when studied in vitro. However, despite their widespread use for potential health benefits, there is a surprising paucity of epidemiologic and experimental studies that address the biologic activities of mushrooms after oral administration to animals or humans. There have been a number of studies that have addressed the ability of mushrooms to modulate mononuclear cell activation and the phenotypic expression of cytokines and their cognate receptors. There have also been a number of attempts to determine antitumor activities of mushrooms. Such studies are important because many of the components of mushrooms do potentially have significant biologic activity. All data, however, should be tempered by the possibility that there are toxic levels of metals, including arsenic, lead, cadmium, and mercury as well as the presence of radioactive contamination with 137Cs. In this review, we will present the comparative biology with respect to both immunological and antitumor activities of mushroom extracts and also highlight the need for further evidence-based research.

Administration, Oral↗
PubMed2004

Fatalities following allergen immunotherapy.

Allergen immunotherapy has been in use for nearly 100 yr and has become an important method of reducing allergic symptoms in select patients with allergic rhinitis, asthma, and insect venom hypersensitivity. Unfortunately, immunotherapy has been associated with anaphylaxis and death. Although the relative risk of severe reactions to immunotherapy is low, the number of such reactions has increased since the introduction of standardized and more potent extracts. There are a number of risk factors associated with such severe anaphylactic reactions. Such risk factors include errors in dosage, failure to reduce the dosage after a longer than scheduled interval, administration of the wrong extract, inadvertent intravenous administration, failure to postpone injection because of infection or asthma exacerbation, failure to observe patients for appropriate length of time, failure to adhere to guidelines for established contraindications, concurrent use of beta-adrenergic blocking agents, uses of mixtures of allergens, immunotherapy during the active allergy season, and types of allergens. In this review, we focus on these and other risk factors in attempts to reduce the risk of anaphylaxis following allergen immunotherapy.

Age Factors↗
PubMed2003

Immunopathogenesis of Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease characterized by the sicca symptoms of dry eyes and dry mouth. Glandular dysfunction is thought to arise from destruction associated with lymphocytic infiltration. The degree of glandular destruction, however, does not correlate with the severity of sicca symptoms, suggesting that other mechanisms are involved, including abnormalities in parasympathetic neurotransmission. Autoantibodies against the muscarinic acetylcholine receptor have been implicated in this process, but multiple other autoantibodies have been found. Cytokines elaborated in the inflammatory lesions also appear to be involved and dysregulation of apoptosis are also involved in the pathogenesis of SS. A new two-stage model of SS has been proposed. First, there is a lymphocyte-independent phase during which inappropriate apoptosis results in the generation of apoptotic autoantigens which then attract lymphocytes. Subsequently, in the second lymphocyte-dependent phase, an immune attack causes further cell death and salivary dysfunction. Although the disease generally takes a rather stable and benign course, patients with SS have a significant risk of developing B cell lymphoma.

Humans↗
PubMed2003

Clinical and immunologic components of sarcoidosis.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology that affects the lungs and the lymphatic system. It is seen by specialists in allergy, rheumatology, and pulmonary disease. Although there are no clues to etiology, an environmental basis has been implicated primarily on the basis of epidemiologic and anecdotal data. The majority of patients are very readily diagnosed and should not be confused with other pulmonary disorders. Sarcoidosis can become an issue if it occurs in the presence of other significant pulmonary disease, such as patients with asthma or hypersensitivity pneumonitis. Most patients remain asymptomatic and many are diagnosed when picked up on a routine screening exam. Steroids can be used to manage some patients but caution should be exercised to choose the appropriate dose and to treat patients for a limited period of time to avoid the complications of steroids. A minority of patients do progress to significant disease, including morbidity and mortality, and further research is needed to determine more appropriate and specific therapy for such situations.

Biomarkers↗
PubMed2002

Microgravity and immune responsiveness: implications for space travel.

To date, several hundred cosmonauts and astronauts have flown in space, yet knowledge about the adaptation of their immune system to space flight is rather limited. It is evident that a variety of immune parameters are changed during and after space flight, but the magnitude and pattern of these changes can differ dramatically between missions and even between crew members on the same mission. A literature search was conducted involving a total of 335 papers published between 1972 and 2002 that dealt with the key words immune response, microgravity and astronauts/cosmonauts, isolation, gravity, and human health. The data from multiple studies suggested that major discrepancies in outcome are due to methodologic differences. However, the data also suggested major factors that affect and modulate the immune response during space travel. In part at least, these discrepancies can be attributed to methodologic differences. In addition, a variety of other features, in particular the types and extent of stressors encountered during space missions, are likely to contribute to the variability of immune responses during and after space flight. That stress plays an important role in the effects of space flight on immunologic parameters is suggested by the frequent findings that stress hormones are upregulated during and after space flight. Unfortunately, however, the existing data on hormonal parameters are almost as varied as those on immunologic changes, and correlations between the two datasets have only rarely been attempted. The functional implications of space flight-induced alterations in immune response largely remain to be elucidated, but the data suggest that long-term travel will be associated with the development of immune-compromised hosts.

Adaptation, Physiological↗
PubMed2002

Vaccines, viruses, and voodoo.

Vaccinations are invaluable in protection from a wide variety of diseases that can cause substantial morbidity and mortality. Although a rare complication of vaccination, autoimmune disorders represent one of these morbidities. Recently, widespread public concern has arisen from case reports suggesting that--similar to what has been observed after natural viral infections--there might be an association between specific immunizations and autoimmune diseases. Herein we address the biological plausibility of such a connection, focusing particularly on the examples of hepatitis B, rubella, and measles-mumps-rubella (MMR) vaccinations, and the autoimmune diseases they are potentially associated with. Our review of the available data suggests that, for the general population, the risk: benefit ratio is overwhelmingly in favor of vaccinations. However, the possibility cannot be ruled out that, in genetically susceptible individuals, vaccination can result in the unmasking of an autoimmune disease triggered by the immunization. We also critically examine the existing data suggesting a link between immunization against MMR and autism, and briefly discuss the controversial evidence pointing to a possible relationship between mercury exposure from vaccines and autistic disorders. There is a continued urgent need for rigorously designed and executed studies addressing these potential associations, although the use of vaccinations remains a critical public health tool for protection against infectious disease.

Adolescent↗