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Biomedical subjects

Carol A Langford

Publications and source records attributed to Carol A Langford.

At least 19 recordsLinked to original sources
PubMed2006

Novel therapeutic strategies for large vessel vasculitis.

Giant cell arteritis and Takayasu's arteritis are systemic vasculitides that cause inflammation of large arteries and their branches. Both have similar histology, but differ in their age of onset. Corticosteroids have been the mainstay of treatment for the past 50 years but are limited by the potential toxicity that may occur in almost 60% of patients. This limitation has lead to the investigation of alternative agents for the treatment of these diseases.

Anti-Inflammatory Agents↗
PubMed2006

Advances in the treatment of small vessel vasculitis.

The systemic small vessel vasculitides encompass Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. The traditional approach to therapy, which incorporates cytotoxic drugs and glucocorticoids, is associated with a significant risk of relapse and treatment-related toxicity. The formation of multicenter collaborative groups has facilitated the execution of randomized controlled trials, and has led to the identification of several effective therapeutic options. This article reviews the existing data and refers to studies in progress that may answer some of the questions that remain regarding the treatment of the small vessel vasculitides.

Anti-Inflammatory Agents↗
PubMed2005

How can relapses be detected and prevented in primary systemic small-vessel vasculitides?

Relapse is an important outcome measure in patients with Wegener's granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome. Although relapses are common in these diseases, it remains unclear why these occur and whether they are influenced by exogenous or endogenous factors. A key to minimizing the consequences of relapse is early recognition through monitoring. This is particularly essential to detect glomerulonephritis that is often asymptomatic and can be rapidly progressive. While the presence of relapse is currently based on objective evidence of active disease, investigations seek to identify factors that may distinguish patients at risk of relapse or markers that reliably predict the occurrence of relapse prior to organ injury. With the ability to successfully induce remission and the toxicities of available therapies, the relapse rate has become a critical issue in assessing the efficacy of new treatments. Recent clinical trials have sought to investigate safer therapeutic options that decrease disease relapse.

Clinical Trials as Topic↗
PubMed2005

Vasculitis in the geriatric population.

Vasculitis represents an uncommon but important group of disease entities that may affect older patients. The most common systemic vasculitic disease in humans is giant cell arteritis, a disease process seen almost exclusively in patients over the age of 50. Vasculitic disease in geriatric patients presents unique challenges with regard to diagnosis and treatment. A thorough understanding of the vasculitic disease entities that may affect older patients as well as their diagnosis and management is essential in minimizing disease and treatment related morbidity and mortality.

Aged↗
PubMed2005

Update on Wegener granulomatosis.

Wegener granulomatosis classically involves clinical disease of the upper airways, lungs, and kidneys. Ninety percent of patients present with symptoms involving the upper or lower airways, or both, and it should be suspected in any patient with pulmonary hemorrhage, glomerulonephritis, mononeuritis multiplex, unexplained multisystem disease, or progressive unresponsive sinus disease. Current treatments induce remission and allow long-term survival.

Antibodies, Monoclonal↗
PubMed2004

Mycophenolate mofetil for remission maintenance in the treatment of Wegener's granulomatosis.

OBJECTIVE: To examine the safety of mycophenolate mofetil (MMF) for remission maintenance in patients with Wegener's granulomatosis (WG) who had been treated with daily cyclophosphamide (CYC) and glucocorticoids to induce remission. METHODS: Fourteen patients were treated for active WG using a standardized regimen of CYC and glucocorticoids for induction of remission and MMF for remission maintenance. Outcome was assessed using predetermined definitions based on clinical characteristics and pathologic, laboratory, and radiographic findings. RESULTS: Remission occurred in all 14 patients (100%) at a median time of 3 months. The median time to discontinuation of glucocorticoids was 8 months. No patients died during protocol treatment and 6 patients (43%) relapsed at a median of 10 months after achieving remission. MMF was well tolerated and no patients had to be withdrawn as a result of medication toxicity. CONCLUSION: The use of CYC and glucocorticoids for induction of remission and MMF for remission maintenance was well tolerated, but disease relapses were observed.

Adult↗
PubMed2004

Wegener's granulomatosis: evolving concepts in treatment.

Wegener's granulomatosis (WG), the most common of the pulmonary granulomatous vasculitides, typically involves the upper respiratory tract, lower respiratory tract (bronchi and lung), and kidney, with varying degrees of disseminated vasculitis. Major histological features include a necrotizing vasculitis involving small vessels, extensive "geographic" necrosis, and granulomatous inflammation. Clinical manifestations of WG are protean; virtually any organ can be involved. Further, the spectrum and severity of the disease is heterogeneous, ranging from indolent disease involving only one site to fulminant, multiorgan vasculitis leading to death. The pathogenesis of WG has not been elucidated, but both cellular and humoral components are involved. Circulating antineutrophil cytoplasmic antibodies (cANCA) likely play a role in the pathogenesis and often correlate with activity of the disease. Treatment strategies are evolving. Cyclophosphamide (CYC) plus corticosteroids (CS) is the mainstay of therapy for generalized, multisystemic WG. Historically, the combination of CYC plus CS was used for a minimum of 12 months, but concern about late toxicities associated with CYC has led to novel treatment approaches. Currently, short-course (3-6 months) induction treatment with CYC plus CS, followed by maintenance therapy with less toxic agents (e.g., methotrexate, azathioprine) is recommended. Further, recent studies suggest that methotrexate combined with CS may be adequate for limited, non-life threatening WG. The role of other immunomodulatory agents (including trimethoprim-sulfamethoxazole) is also explored.

Journal Article↗
PubMed2004

Biologic immunomodulatory therapies in the vasculitic diseases.

The expanding range of biologic agents capable of modulating the immune response has opened up a new realm for therapeutic exploration in the vasculitic diseases. Partnered with increasing knowledge regarding the mechanisms of vascular inflammation, these agents have raised the question as to whether it may be possible to treat systemic vasculitis syndromes by selectively targeting pathways involved in disease pathogenesis. The action of these agents to directly modulate specific immunologic components offers the potential not only to impact disease activity but also to reduce the risk of morbidity that can result from currently available treatment options. The study of biologic therapies in the vasculitides must, however, be approached with caution because unanticipated effects on disease activity and disease-specific toxicities can occur. The only biologic agent that has currently been shown to have therapeutic efficacy in a systemic vasculitis syndrome is interferon-alpha in the treatment of hepatitis C-associated cryoglobulinemic vasculitis. The use of biologic agents to treat other vasculitides remains investigational. Methodical evaluation of biologic agents prior to their use in general clinical practice is essential to understand their safety and efficacy. Rigorous, standardized investigations may also provide important insights into pathogenesis of the vasculitic diseases.

Journal Article↗
PubMed2004

Polyarteritis nodosa reports to the vaccine adverse event reporting system (VAERS): implications for assessment of suspected vaccine-provoked vasculitis.

OBJECTIVE: To examine polyarteritis nodosa (PAN) reports to the Vaccine Adverse Event Reporting System (VAERS) as the initial stage in investigating the hypothesis that vaccination can very rarely cause PAN. METHODS: We reviewed PAN reports submitted from 1990 through 2001 using a causal inference framework to evaluate the consistency of the reports' clinical details with this hypothesis. We also reviewed published literature relating to the hypothesized association's biological plausibility. RESULTS: VAERS received 25 PAN reports. Ten met our case definition for definite or possible PAN and had no alternative etiology for PAN identified. Nine of these 10 followed hepatitis B vaccine with a modal peak (4 definite cases) in time to symptom onset 2 weeks after vaccination. However, all potential triggering infections were not excluded, and identification of vaccine antigens in clinical specimens was not attempted. Also, 14 of 25 reports were European, with 11 from France. All 9 French reports with a known diagnosis date began during 1994-97, when autoimmune and rheumatologic events following hepatitis B vaccine were a focus of public concern in France. CONCLUSION: While we identified some supportive evidence, overall, current adverse event reports do not support a causal link between vaccination and PAN. Appropriate prospective evaluation of future post-vaccination PAN cases could add to current knowledge with rigorous confirmation of diagnosis, appropriate testing for possible triggering infections including polymerase chain reaction testing for latent hepatitis B infection, and an attempt to link the vaccine antigen to pathology such as by immunohistochemical staining or immune complex identification.

Adolescent↗
PubMed2003

Wegener's granulomatosis: current and upcoming therapies.

Wegener's granulomatosis is a complex multisystem disease that can be associated with morbidity and mortality. The introduction of cyclophosphamide and glucocorticoids brought about the potential for long-term survival and provided the opportunity and impetus to explore treatment options that can reduce the toxicity of therapy and lessen the likelihood of relapse. With the growth of knowledge regarding disease pathophysiology and the increasing ability to selectively target the immune system, the potential options for therapeutic investigation have continued to expand. Careful study of new agents through rigorously designed trials is essential to answering questions of safety and efficacy in Wegener's granulomatosis.

Clinical Trials as Topic↗
PubMed2003

Use of a cyclophosphamide-induction methotrexate-maintenance regimen for the treatment of Wegener's granulomatosis: extended follow-up and rate of relapse.

PURPOSE: To determine the relapse rate and outcome in patients with Wegener's granulomatosis treated with daily cyclophosphamide and glucocorticoids to induce remission followed by methotrexate for remission maintenance. METHODS: We performed an open-label prospective study in 42 patients with active Wegener's granulomatosis. All patients were treated with a standardized regimen. Outcomes were assessed using predetermined definitions based on clinical characteristics and pathologic, laboratory, and radiographic findings. RESULTS: All patients achieved disease remission. The median time to remission was 3 months, and the median time to discontinuation of glucocorticoids was 8 months. During a median of 32 months of follow-up, 1 patient died (of a myocardial infarction not related to vasculitis). Two patients (5%) had to withdraw from the study because of medication toxicity. Twenty-two patients (52%) relapsed, with glomerulonephritis occurring in 16 patients. Of these 16 patients, 4 had an increase of >0.2 mg/dL in serum creatinine level. All 4 patients returned to their prior level of renal function with treatment. None of the 22 relapses met the criteria for severe disease. CONCLUSION: The use of cyclophosphamide and glucocorticoids for induction and methotrexate for maintaining remission is an effective and well-tolerated therapeutic approach in patients with active Wegener's granulomatosis.

Adolescent↗
PubMed2003

Tarsal-conjunctival disease associated with Wegener's granulomatosis.

OBJECTIVE: To describe the clinical characteristics of tarsal-conjunctival disease in a cohort of patients with Wegener's granulomatosis (WG). DESIGN: Retrospective, case-controlled study. PARTICIPANTS: The medical records of 82 consecutive WG patients who underwent an eye examination between January 1996 and June 2002 at the National Institutes of Health were reviewed. METHODS: Details of the ophthalmic examination, results of medical therapy, and histopathologic analysis results were recorded. Tarsal-conjunctival disease was defined by (1). conjunctival hyperemia and granuloma formation, areas of necrosis, or active fibrovascular changes in the tarsus or conjunctiva, or (2). evidence of inactive fibrovascular scar. The association of tarsal-conjunctival disease with major organ system involvement was assessed using Bayesian methods. MAIN OUTCOME MEASURES: The occurrence and clinical characteristics of tarsal-conjunctival disease in a cohort of patients with WG and associations with major organ system involvement. RESULTS: Tarsal-conjunctival disease occurred in 13 of 82 patients (16%) with WG examined over a 6.5-year period. The palpebral surface of the upper lid was involved most commonly, showing conjunctival hyperemia in seven patients, granulomatous lesions in three patients, tarsal-conjunctival necrosis in four patients, active fibrovascular proliferation in six patients, and inactive fibrous scar tissue in seven patients. Histopathologic analysis of eyelid biopsy specimens showed granulomatous inflammation, focal necrosis, and areas of occlusive vasculitis in the tarsus and conjunctiva. In reviewing the patterns of organ involvement in patients with and without tarsal-conjunctival disease, the association of subglottic stenosis and nasolacrimal duct obstruction with tarsal-conjunctival disease showed a high probability of clinical significance. CONCLUSIONS: Tarsal-conjunctival disease, a previously uncommon finding in patients with WG, was characterized by inflammation of the palpebral conjunctiva and tarsus followed by a fibrovascular proliferation and scar formation. Because of the important association of tarsal-conjunctival disease with subglottic stenosis, which can progress and lead to laryngeal obstruction and respiratory failure, patients with tarsal-conjunctival disease should be referred to an otolaryngologist for evaluation.

Adult↗
PubMed2003

15. Vasculitis.

Vasculitis is histologically defined by the presence of blood vessel inflammation. It can be observed in a wide variety of settings, either occurring secondarily to another process or as the pathologic foundation of a primary vasculitic disease. The primary systemic vasculitides comprise a broad group of disease entities that are uniquely identified by the nature of their clinical, histopathologic, or therapeutic characteristics. Individual diseases often predominantly affect blood vessels of a particular size, the pattern of which influences their clinical manifestations and has been used in their classification. The vasculitides span a wide range of disease severity, extending from illnesses that rarely produce death to those almost universally fatal before the introduction of effective therapy. Immunosuppressive and cytotoxic agents are used to treat many vasculitic diseases. Although such approaches can be effective, long-term treatment may be complicated by chronic sequelae from organ damage, disease relapses, and medication side effects. Recent investigations have focused on understanding the pathophysiology of these diseases, which may lead to more efficacious and less toxic therapeutic options.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2003

Biologic therapies in the vasculitides.

Monoclonal antibody and recombinant DNA technologies have led to the development of biologic therapies capable of directly targeting selected components of the immune response. With the steady expansion of knowledge regarding the mechanisms of vascular inflammation, the safety and efficacy of biologic agents in the vasculitic diseases are being increasingly investigated. By targeting specific effector mechanisms involved in the pathogenesis of vasculitis, these agents may provide a less toxic means of inducing remission and lessening relapse. However, the study of biologic therapies in the vasculitides must be approached with caution, as unanticipated effects on disease activity and disease-specific toxicities can occur. Studies to examine these agents must recognize the potential for active vasculitis to be organ- or life-threatening as well as the current existence of effective therapies. In the research setting, investigation of biologic agents in the treatment of vasculitic diseases may also provide important insights into pathogenesis of these syndromes.

Animals↗
PubMed2003

New insights into the immunopathogenesis and treatment of small vessel vasculitis of the kidney.

PURPOSE OF REVIEW: Glomerulonephritis is an important manifestation of small vessel vasculitides such as Wegener granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Renal involvement in these diseases is characterized by a pauci-immune segmental necrotizing and crescentic glomerulonephritis that is strongly associated with circulating antineutrophil cytoplasmic autoantibodies. We will review recent advances in understanding the pathogenesis of antineutrophil cytoplasmic autoantibody-related renal vasculitides and innovative approaches to their treatment. RECENT FINDINGS: An experimental milestone in antineutrophil cytoplasmic autoantibody research has been reached in the past year. Using an innovative mouse model, investigators from the University of North Carolina in Chapel Hill have recently acquired robust data supporting the pathogenic role of antineutrophil cytoplasmic autoantibodies in the glomerulonephritis and small vessel vasculitis, analogous to those seen in microscopic polyangiitis and Wegener granulomatosis. Novel immunosuppressive approaches have been examined including preliminary studies using biologic agents, such as antagonists of tumor necrosis factor and monoclonal antibodies to B lymphocytes. SUMMARY: Recent insights into the pathogenesis of antineutrophil cytoplasmic autoantibody-related vascular injury and the availability of new biologic, immune response modifiers to complement standard chemical immunosuppressive agents offer exciting new prospects for investigation in the management of patients with small vessel renal vasculitides.

Adjuvants, Immunologic↗