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Response Modifier (response + modifier)
Kinds of Response Modifier Selected AbstractsEruptive Epidermoid Cysts Resulting from Treatment with ImiquimodDERMATOLOGIC SURGERY, Issue 7 2005Chelsy L. Marty MD Background Because of its unique mechanism of action and safety profile, imiquimod, a topical immune response modifier, is used for many benign and malignant dermatologic conditions. Adverse effects are typically limited to treatment site erythema and erosion. Objective To describe a newly recognized adverse effect of imiquimod. Methods A 79-year-old woman being treated with imiquimod 5 days per week for a nodular basal cell developed a verrucous plaque over the treatment area after 7 weeks of therapy. Results Scouting biopsies demonstrated multiple comedones and ruptured epidermoid cysts. There was no evidence of residual basal cell carcinoma. Conclusions Imiquimod is a new and novel treatment option for cutaneous malignancies. We report its successful use in the treatment of a nodular basal cell carcinoma. The multiple comedones and ruptured epidermoid cysts are newly reported adverse effects of imiquimod therapy. [source] Imiquimod Treatment of Superficial and Nodular Basal Cell Carcinoma: 12-Week Open-Label TrialDERMATOLOGIC SURGERY, Issue 3 2005Ketty Peris MD Background Imiquimod is an immune response modifier shown to be effective in basal cell carcinoma (BCC). Objective To evaluate the efficacy, tolerability, and response durability of imiquimod 5% cream in selected patients with superficial and/or nodular BCCs. Methods Seventy-five superficial and 19 nodular BCCs in 49 patients were treated with imiquimod once daily three times a week for up to 12 weeks. Results Of the 49 enrolled patients, 1 discontinued the study and 1 was lost to follow-up. After 12 weeks of treatment, a complete response occurred in 70 of 75 (93.3%) superficial BCCs and a partial response in 4 of 75 (5.3%) superficial BCCs. Ten of 19 (52.6%) nodular BCCs cleared after 12 weeks, whereas 7 (36.8%) showed partial remission. Adverse side effects were limited to local skin reactions. Recurrence was observed in 2 of 70 (2.9%) successfully treated superficial BCCs 6 and 8 months after treatment discontinuation. No recurrence was detected in 68 of 70 (97.1%) superficial BCCs and in 10 successfully treated nodular BCCs after 12 to 34 months of follow-up (mean 23 months). Conclusions In our patient population, treatment of superficial BCCs with topical imiquimod for 12 weeks produced an excellent clinical response overall, with complete remission maintained after a mean of 23 months. KETTY PERIS, MD, ELENA CAMPIONE, MD, TAMARA MICANTONIO, MD, GEORGIANA CLARE MARULLI, MD, MARIA CONCETTA FARGNOLI, MD, AND SERGIO CHIMENTI, MD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS. [source] Noninvasive Imaging, Treatment, and Microscopic Confirmation of Clearance of Basal Cell CarcinomaDERMATOLOGIC SURGERY, Issue 3 2003Mark Goldgeier MD BACKGROUND. The diagnosis of basal cell carcinoma (BCC) is generally established by skin biopsy followed by tissue preparation and microscopic analysis. Treatment of BCC is often accomplished by surgical excision. Objective. To confirm the presence of BCC with a noninvasive imaging technique, to treat the patient with a topical immune response modifier, and to confirm the clearance of BCC noninvasively. METHODS. Confocal microscopy (CM) is a noninvasive technique for real-time imaging of skin in vivo. Imiquimod, an immune response modifier, is applied topically by the patient to the skin lesion. RESULTS. The presence of BCC was confirmed with CM. Posttreatment CM imaging confirmed the clearance of BCC from the entire treatment field. Both the pretreatment and the posttreatment CM findings were confirmed by invasive biopsy. CONCLUSION. The ability to use CM to image in real time without discomfort to the patient makes it a powerful tool to assist in the diagnosis of skin disease. [source] Association of immunological disorders in lethal side effect of NSAIDs on ,-glucan-administered miceFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2001Hideaki Takahashi Abstract (1,3)-,- d -Glucan (,-glucan) is a biological response modifier that regulates host immune response. We have found that the combination of a ,-glucan and a non-steroidal anti-inflammatory drug (NSAID), indomethacin (IND), induced lethal toxicity in mice [Yoshioka et al. (1998) FEMS Immunol. Med. Microbiol., 21, 171,179]. This study was undertaken to analyze the mechanism of the lethal side effect. Combination of a ,-glucan and IND increased the number of leukocytes, especially macrophages and neutrophils, in various organs and these cells were activated. The activated state of these cells was supported by the enhanced production of interferon-, in the presence of IND in vitro culture of the peritoneal exudate cells. Intestinal bacterial flora was translocated into the peritoneal cavity in these mice to cause peritonitis. Comparing the toxicity of various NSAIDs, nabumetone, a partially cyclooxygenase-2-selective NSAID with weaker toxicity to the gastrointestinal tract, did not exhibit a lethal side effect. These facts strongly suggested that gastrointestinal damage by NSAIDs was more severe in ,-glucan-administered mice, resulting in peritonitis by enteric bacteria and leading to death. [source] Current modalities and new advances in the treatment of basal cell carcinomaINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2006Roger I. Ceilley MD Basal cell carcinoma (BCC) is one of the most common cancers. Surgical extirpation is currently the standard of care for BCC, which is associated with several advantages and disadvantages. Procedures such as surgical excision used to treat superficial BCC (sBCC) and nodular BCC (nBCC) may have high 5-year recurrence rates if tumors are not completely excised. Curettage with electrodesiccation is a common method for treating primary BCC. However, multiple cycles are recommended and the procedure can have unsatisfactory cosmetic results (e.g. scarring and hypopigmentation). Mohs micrographic surgery has a low rate of disease recurrence but is a specialized procedure usually limited to specific indications (e.g. high-risk tumors). Cryosurgery and photodynamic therapy require multiple cycles and are associated with variable cosmetic outcomes and recurrence rates. As with any procedure, potential risks and patient quality-of-life issues need to be considered. In addition, substantial patient and healthcare provider inconvenience limit the practical utility of some modalities. Pharmacologic interventions provide another treatment option as adjunctive or monotherapy. Investigations of imiquimod, a novel immune response modifier, have indicated that this topical, noninvasive agent is safe and well tolerated and may be efficacious in the treatment of BCC. This review will highlight the role of standard treatment modalities and introduce new advances in the treatment of BCC. [source] Imiquimod 5% cream: a topical immune response modifierINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2002Mario Marini PhD No abstract is available for this article. [source] Enhanced type I interferon signaling and recruitment of chemokine receptor CXCR3-expressing lymphocytes into the skin following treatment with the TLR7-agonist imiquimodJOURNAL OF CUTANEOUS PATHOLOGY, Issue 4 2005Joerg Wenzel Introduction:, Imiquimod (AldaraÔ) is an immune response modifier approved for the topical treatment of external genital and perianal warts which can mediate regression of several cutaneous malignancies [basal cell carcinoma (BCC), Bowen's disease, actinic keratosis, and metastasis of malignant melanoma]. Recently, it was discovered that imiquimod acts through the toll-like receptor (TLR) 7. We hypothesize that TLR7-signaling strongly induces the production of interferon (IFN) ,, which is able to enhance Th1-mediated cellular antiviral and antitumor immunity. Patients and methods:, In the present study we analyzed the expression of MxA, a protein specifically induced by type I IFNs during topical imiquimod treatment in several patients suffering from different cutaneous malignancies (BCC, cutaneous metastasis of melanoma, and breast cancer), and characterized the inflammatory infiltrate, along with the expression of chemokine receptor CXCR3, by immunohistochemistry. Results:, Treatment with the TLR7-agonist imiquimod induced a significant lesional lymphocytic inflammation, associated with strong expression of MxA, indicating the induction of type I IFN signaling. The extent of lesional MxA staining closely correlated with the number of infiltrating T lymphocytes and the expression of the chemokine receptor CXCR3, characteristic for Th1-biased immune responses. Discussion:, Our in vivo results suggest an important role for TLR7-induced production of type I IFN, which links innate and adaptive immunity and promotes specific Th1-biased cellular immune response capable of eliminating cutaneous malignancies. MxA appears to be a valuable parameter to demonstrate IFN-type I expression in imiquimod therapy. [source] Effects of hydrolyzed Chlorella vulgaris by malted barley on the immunomodulatory response in ICR mice and in Molt-4 cellsJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 9 2010Na-Hyung Kim Abstract BACKGROUND:Chlorella vulgaris is a unicellular and microscopic algae that is currently used in a variety of forms of tablets, capsules and liquid as a biological response modifier. The aim of this study was to investigate the effects of hydrolyzed Chlorella vulgaris by malted barley for its potential reduction of the immobility time in ICR mice and on the cytokine regulation in human T cell line, Molt-4. RESULTS: After a forced swimming test, the changes in aspects of blood biochemical parameters due to the administration of hydrolyzed Chlorella vulgaris by malted barley were examined. The effect of hydrolyzed Chlorella vulgaris by the malted barley-treated group for 14 days on the immobility time was significantly reduced in comparison with that of the control group (P < 0.01). The plasma level of blood urea nitrogen was significantly decreased in hydrolyzed Chlorella vulgaris by malted barley-treated group compared with the control group (P < 0.05). In addition, hydrolyzed Chlorella vulgaris by malted barley increased interferon-, and interlukin-2 levels in Molt-4 cells. CONCLUSION: These results indicate that hydrolyzed Chlorella vulgaris by malted barley is useful for immune function improvements, enhanced physical stamina, and as a candidate for an anti-fatigue or antidepressant agent. Copyright © 2010 Society of Chemical Industry [source] Resolution of vulvitis circumscripta plasmacellularis with topical imiquimod: two case reportsBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2003H.L. Ee Summary Vulvitis circumscripta plasmacellularis (VCP) is a rare but well-described entity. It is notorious for its recalcitrant nature to various modalities of treatment. Intralesional interferon-, showed some promise, with complete resolution, but is coupled with the side-effect of myelosuppression. Topical imiquimod is a novel immune response modifier with the ability to induce the production of interferon-,. In this paper, we report two cases of VCP whose lesions were resistant to antibiotics, topical and oral corticosteroids, but resolved after a treatment trial with imiquimod. [source] Diffuse large B-cell lymphoma in a patient with rheumatoid arthritis treated with infliximab and methotrexateCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 4 2008C. Nakashima Summary Infliximab is a tumour necrosis factor (TNF)-, blocking drug classified as a biological response modifier. It has been suggested that the risk of malignancies, especially lymphomas, is increased in patients with rheumatoid arthritis (RA) treated with anti-TNF-, antibody therapy. We present a case of malignant lymphoma during the treatment of RA with infliximab and methotrexate. [source] Successful treatment of extramammary Paget's disease of the scrotum with imiquimod 5% creamCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 2003B. Berman Summary Extramammary Paget's disease (EMPD) of the skin is an uncommon malignancy involving the epidermis, which sometimes extends into the dermis. Current treatments for EMPD are surgical excision, Mohs' micrographic surgery or laser ablation. We report a case of a 68-year-old male who presented with recurrent EMPD. The patient refused to have surgery and, as an alternative, he applied imiquimod 5% cream, an immune response modifier, daily for a total of 6 weeks. During the initial weeks of therapy, he experienced moderate erythema. Imiquimod treatment resulted in clinical and histological eradication of EMPD, with no recurrence observed during 6 months of follow-up. [source] Actinic keratosis treated with an immune response modifier: a case report of six patientsCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 2003L. Bianchi Summary Actinic keratoses (AKs) are intraepidermal tumours, which result from the proliferation of transformed neoplastic keratinocytes. They are typically induced by chronic exposure to ultraviolet radiation, and can often develop into squamous cell carcinoma (SCC). Six patients, who presented with AKs located on the head, face and chest, were treated with the immune response modifier, imiquimod, as a 5% cream five times per week for up to 8 weeks. The majority of patients experienced mild to moderate side-effects, consisting of erythema, itching and burning. Topical application of imiquimod for 4,8 weeks resulted in complete clearance in all patients. No new or recurrent lesions were observed during a 6,8 month follow-up period. [source] Perioperative Management of Medications for Psoriasis and Psoriatic Arthritis: A Review for the DermasurgeonDERMATOLOGIC SURGERY, Issue 4 2008CLAUDIA HERNANDEZ MD BACKGROUND Psoriasis affects an estimated 3% of the world's population. Many are on chronic immunosuppressive therapy for the cutaneous and joint manifestations of this disorder. The management of these medications in the perioperative period is controversial. Psoriasis and psoriatic arthritis medications can affect wound healing, hemostasis, and infection risk during cutaneous surgery. OBJECTIVES The objective of this article is to provide a critical review of various medications used for care of the psoriatic patient and their potential effect on cutaneous surgical procedures. CONCLUSIONS This review summarizes current understanding of wound healing, hemostatic effects, and infectious risks regarding many psoriasis medications including nonsteroidal anti-inflammatory drugs, cyclooxygenase inhibitors, corticosteroids, various immunosuppressants, and biologic response modifiers. Recommendations vary depending on the agent in question, type of procedure, and comorbid conditions in the patient. Caution is advised when using many of the medications reviewed due to lack of human data of their effects in the perioperative period. [source] Immune response modifiers , mode of actionEXPERIMENTAL DERMATOLOGY, Issue 5 2006Meinhard Schiller Abstract:, The innate immune system governs the interconnecting pathways of microbial recognition, inflammation, microbial clearance, and cell death. A family of evolutionarily conserved receptors, known as the Toll-like receptors (TLRs), is crucial in early host defense against invading pathogens. Upon TLR stimulation, nuclear factor-,B activation and the interferon (IFN)-regulatory factor 3 pathway initiate production of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor-,, and production of type I IFNs (IFN-, and IFN-,), respectively. The innate immunity thereby offers diverse targets for highly selective therapeutics, such as small molecular synthetic compounds that modify innate immune responses. The notion that activation of the innate immune system is a prerequisite for the induction of acquired immunity raised interest in these immune response modifiers as potential therapeutics for viral infections and various tumors. A scenario of dermal events following skin cancer treatment with imiquimod presumably comprises (i) an initial low amount of pro-inflammatory cytokine secretion by macrophages and dermal dendritic cells (DCs), thereby (ii) attracting an increasing number type I IFN-producing plasmacytoid DCs (pDCs) from the blood; (iii) Langerhans cells migrate into draining lymph nodes, leading to an increased presentation of tumor antigen in the draining lymph node, and (iv) consequently an increased generation of tumor-specific T cells and finally (v) an accumulation of tumoricidal effector cells in the treated skin area. The induction of predominately T helper (Th)1-type cytokine profiles by TLR agonists such as imiquimod might have further benefits by shifting the dominant Th2-type response in atopic diseases such as asthma and atopic dermatitis to a more potent Th1 response. [source] Biologic therapy in the management of extraintestinal manifestations of inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 11 2007Arthur Barrie MD Abstract The inflammatory bowel diseases (IBD), notably Crohn's disease (CD) and ulcerative colitis (UC), are systemic inflammatory diseases primarily involving the gastrointestinal tract. Twenty percent to 40% of patients with IBD develop extraintestinal inflammation and symptoms, known as extraintestinal manifestations (EIMs).1,7 The most common EIMs affect the joints, skin, eyes, and biliary tract. The EIMs associated with IBD bear a negative impact on patients with UC and CD. Thus, the successful treatment of EIMs is essential for improving the quality of life of IBD patients. For most EIMs, their resolution often parallels that of the active IBD in both timing and therapy required. However, some EIM such as axial arthritis, pyoderma gangrenosum, uveitis, and primary sclerosing cholangitis run a clinical course independent of IBD disease activity. The advent of biologic response modifiers, e.g., tumor necrosis factor-, (TNF) inhibitors, has improved the treatment of IBD and its associated EIMs. This article reviews the therapeutic experiences of the 2 most widely used anti-TNF neutralizing antibodies, infliximab and adalimumab, for immune-mediated EIM of IBD. (Inflamm Bowel Dis 2007) [source] Cytokines and Cognition,The Case for A Head-to-Toe Inflammatory ParadigmJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 12 2002Craig J. Wilson MBBS The brain is not only immunologically active of its own accord, but also has complex peripheral immune interactions. Given the central role of cytokines in neuroimmmunoendocrine processes, it is hypothesized that these molecules influence cognition via diverse mechanisms. Peripheral cytokines penetrate the blood-brain barrier directly via active transport mechanisms or indirectly via vagal nerve stimulation. Peripheral administration of certain cytokines as biological response modifiers produces adverse cognitive effects in animals and humans. There is abundant evidence that inflammatory mechanisms within the central nervous system (CNS) contribute to cognitive impairment via cytokine-mediated interactions between neurons and glial cells. Cytokines mediate cellular mechanisms subserving cognition (e.g., cholinergic and dopaminergic pathways) and can modulate neuronal and glial cell function to facilitate neuronal regeneration or neurodegeneration. As such, there is a growing appreciation of the role of cytokine-mediated inflammatory processes in neurodegenerative diseases such as Alzheimer's disease and vascular dementia. Consistent with their involvement as mediators of bidirectional communication between the CNS and the peripheral immune system, cytokines play a key role in the hypothalamic-pituitary-adrenal axis activation seen in stress and depression. In addition, complex cognitive systems such as those that underlie religious beliefs, can modulate the effects of stress on the immune system. Indirect means by which peripheral or central cytokine dysregulation could affect cognition include impaired sleep regulation, micronutrient deficiency induced by appetite suppression, and an array of endocrine interactions. Given the multiple levels at which cytokines are capable of influencing cognition it is plausible that peripheral cytokine dysregulation with advancing age interacts with cognitive aging. [source] Simple assay for antitumour immunoactive glycoprotein derived from Chlorella vulgaris strain CK22 using ELISAPHYTOTHERAPY RESEARCH, Issue 6 2002Kiyoshi Noda Abstract A quantitative ELISA system was developed using a monoclonal antibody (MAb) specific for an antitumour immunoactive glycoprotein (CVS) derived from C. vulgaris strain CK22. The full measuring range of the assay extends from 0.63 to 10.0,ng/mL of CVS. Although no cross-reaction was observed to proteins tested or other biological response modifiers (BRMs) derived from different sources, cross-reactions were found with culture supernatants from two other strains of C. vulgaris having a strong antitumour immunoactivity. Treatment of CVS with protease, acid or alkali weakened or completely eliminated the reactivity against the MAb and also its antitumour immunoactivities. This ELISA system is suitable for the biologically active form of CVS derived from C. vulgaris strain CK22 and related immunoactive strains. Copyright © 2002 John Wiley & Sons, Ltd. [source] Inflammatory protein profile during systemic high dose interleukin-2 administrationPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 2 2006Leonardo Rossi Abstract Systemic interleukin-2 (IL-2) administration induces an assortment of downstream effects whose biological and therapeutic significance remains unexplored mostly because of the methodological inability to globally address their complexity. Protein array analysis of sera from patients with renal cell carcinoma obtained prior and during high-dose IL-2 therapy had previously revealed extensive alterations in expression of the soluble factors analyzed, whose discovery was limited by the number of capture antibodies selected for protein detection. Here, we expanded the analysis to SELDI-TOF-MS and quantitative protein analysis (nephelometry). All cytokines/chemokines detected by protein arrays were below the SELDI detection limit, while novel IL-2-specific changes in expression of acute-phase reactants and high-density lipoprotein metabolites could be identified. Serum amyloid protein,A (SAA) and C-reactive protein expression were consistently up-regulated after four doses of IL-2, while other proteins were down-regulated. These findings were confirmed by SELDI immunoaffinity capture and nephelometry. Immunoaffinity capture revealed different, otherwise undetectable, isoforms of SAA. A linear correlation between peak area by SELDI and protein concentration by nephelometry was observed. Overall distinct yet complementary information was obtained using different platforms, which may better illustrate complex phenomena such as the systemic response to biological response modifiers. [source] Determination of Sample Sizes for Demonstrating Efficacy of Radiation CountermeasuresBIOMETRICS, Issue 1 2010Ralph L. Kodell Summary In response to the ever increasing threat of radiological and nuclear terrorism, active development of nontoxic new drugs and other countermeasures to protect against and/or mitigate adverse health effects of radiation is ongoing. Although the classical LD50 study used for many decades as a first step in preclinical toxicity testing of new drugs has been largely replaced by experiments that use fewer animals, the need to evaluate the radioprotective efficacy of new drugs necessitates the conduct of traditional LD50 comparative studies (FDA, 2002,,Federal Register,67, 37988,37998). There is, however, no readily available method to determine the number of animals needed for establishing efficacy in these comparative potency studies. This article presents a sample-size formula based on Student's,t,for comparative potency testing. It is motivated by the U.S. Food and Drug Administration's (FDA's) requirements for robust efficacy data in the testing of response modifiers in total body irradiation experiments where human studies are not ethical or feasible. Monte Carlo simulation demonstrated the formula's performance for Student's,t, Wald, and likelihood ratio tests in both logistic and probit models. Importantly, the results showed clear potential for justifying the use of substantially fewer animals than are customarily used in these studies. The present article may thus initiate a dialogue among researchers who use animals for radioprotection survival studies, institutional animal care and use committees, and drug regulatory bodies to reach a consensus on the number of animals needed to achieve statistically robust results for demonstrating efficacy of radioprotective drugs. [source] | |||||||||||||