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Biomedical subjects

M Boguniewicz

Publications and source records attributed to M Boguniewicz.

At least 19 recordsLinked to original sources
PubMed2006

Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report.

There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.

Adult↗
PubMed2001

Pathophysiologic mechanisms in atopic dermatitis.

Atopic dermatitis is a common, chronic inflammatory skin disease that frequently predates the development of asthma and/or allergic rhinoconjunctivitis. Recent studies have provided new insights into how the complex interrelationship of genetic, environmental, and immunologic factors may contribute to the development of atopic dermatitis. This article examines some of the factors involved in chronic cutaneous inflammation in this disease. Greater understanding of the mechanisms that underlie the pathophysiology of atopic dermatitis may lead to improved treatment strategies for this increasingly common skin disease.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Fibronectin and fibrinogen contribute to the enhanced binding of Staphylococcus aureus to atopic skin.

BACKGROUND: Staphylococcus aureus colonizes the skin lesions of more than 90% of patients with atopic dermatitis (AD). The mechanism for increased S aureus colonization in AD is unknown. However, the initial event in colonization requires adherence of S aureus to the skin. OBJECTIVE: The purpose of this study was to examine the roles of various bacterial adhesins on S aureus binding to AD skin. METHODS: In an attempt to delineate the mechanism behind this adherence process, an in vitro bacterial binding assay was developed to quantitate the adherence of various S aureus strains to AD, psoriatic, and normal skin sections. S aureus strains used in this study were obtained either from cultures of AD skin lesions or from genetically manipulated strains of S aureus that lacked specific microbial surface components recognizing adhesive matrix molecules (MSCRAMMs)--namely, fibronectin-binding protein (Fnbp), fibrinogen-binding protein (Clf), collagen-binding protein (Cna), and their parent strains. In addition, S aureus strains from patients with AD were pretreated with fibronectin or fibrinogen to block MSCRAMM receptors and interfere with binding. RESULTS: Under all experimental conditions, binding of S aureus was localized primarily to the stratum corneum. Immunocytochemical staining of AD skin sections showed a redistribution of fibronectin to the cornified layer, an observation not seen in normal skin. S aureus binding to uninvolved AD skin was significantly greater than the binding to uninvolved psoriatic skin (P <.0001) and normal skin (P <.0005). The Fnbp-negative S aureus showed a significant reduction in binding to the AD skin (P <.0001) but not to the psoriatic and normal skin. In the AD skin, a significant reduction in the binding of S aureus was also observed in the Clf-negative strain (P <.0001) but not in the Cna-negative S aureus. Preincubation of S aureus with either fibronectin or fibrinogen also inhibited bacterial binding to AD skin (P <.0001). CONCLUSION: These data suggest that fibronectin and fibrinogen--but not collagen--play a major role in the enhanced binding of S aureus to the skin of patients with AD.

Bacterial Adhesion↗
PubMed2000

Evidence for increased expression of eotaxin and monocyte chemotactic protein-4 in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with tissue eosinophilia and the activation of T lymphocytes. The novel eosinophil chemoattractants, eotaxin and monocyte chemotactic protein (MCP)-4, are up-regulated at sites of allergic inflammation, yet their contribution to the pathophysiologic mechanisms of AD remains to be determined. OBJECTIVE: We sought to investigate the expression of eotaxin and MCP-4 in acute and chronic lesions from patients with AD and to determine their relationship to the numbers of resident inflammatory cells. METHODS: With use of in situ hybridization, the expression of eotaxin and MCP-4 messenger RNA (mRNA) in skin biopsy specimens from patients with acute and chronic AD skin lesions was compared with that of uninvolved skin from these patients and skin from healthy volunteers. RESULTS: There was a constitutive expression of eotaxin and MCP-4 mRNA in skin biopsy specimens from healthy subjects. Positive signal for chemokine mRNA was observed both within the epidermis and inflammatory cells (macrophages, eosinophils, and T cells) of the subepidermis in AD skin lesions. Within the subepithelium acute and chronic skin lesions exhibited a significant increase in the numbers of eotaxin and MCP-4 mRNA-positive cells compared with uninvolved skin (P <.01), whereas the numbers of eotaxin and MCP-4 mRNA-positive cells were significantly higher in chronic AD compared with acute AD skin lesions (P <.005, P <.001, respectively). Correlations were observed between the expression of eotaxin and MCP-4 mRNA and the presence of eosinophils and macrophages, respectively, in AD lesions (r(2) = 0.84, r(2) = 0.94). CONCLUSION: There is an increased expression of eotaxin and MCP-4 in acute and chronic lesions, suggesting that these chemotactic factors play a major role in the pathophysiologic mechanisms of AD.

Biopsy↗
PubMed1999

Understanding and treating atopic dermatitis.

Atopic dermatitis is a chronic, relapsing inflammatory pruritic skin disease commonly associated with respiratory allergy. The keys to successful management of this disease continue to include accurate diagnosis, hydration of the skin, control of pruritus and infections, appropriate use of topical corticosteroids and emollients, and identification and elimination of exacerbating factors. Treatment can be complicated and educating the patient regarding disease and therapy is critical for success.

Administration, Cutaneous↗
PubMed1998

In vivo expression of cytokine receptor mRNA in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with immunopathologic features that vary depending on the duration of the lesion. Acute lesions are associated with a T-cell infiltrate and a high expression of IL-4 mRNA compared with chronic lesions, uninvolved AD skin, or skin from normal control subjects. Chronic lesions are rich in eosinophils and monocyte/macrophages and contain a greater number of IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-12 (p40) mRNA-positive cells. OBJECTIVES: In this study, we investigated the mRNA expression of the IL-4 receptor (IL-4Ralpha), IL-5Ralpha, GM-CSFRalpha, and IL-12Rbeta2 in biopsy specimens from acute and chronic AD lesions, uninvolved AD skin, normal skin, and psoriatic skin lesions. METHODS: Cytokine receptor mRNA was examined in paraformaldehyde-fixed biopsy specimens with in situ hybridization with specific antisense riboprobes. RESULTS: Acute and chronic skin lesions exhibited a significant increase in numbers of IL-5Rbeta and GM-CSFRalpha mRNA-positive cells compared with uninvolved AD skin and normal skin (P < .001). Chronic skin lesions had a significantly greater number of IL-5Ralpha and GM-CSFRalpha mRNA-positive cells when compared with acute AD skin (P < .001). In contrast, IL-4Ralpha mRNA expression was increased in acute but not chronic AD lesions compared with uninvolved and normal skin (P < .001). No significant differences were observed in numbers of IL-12Rbeta2 mRNA-positive cells when comparing acute AD, chronic AD, uninvolved AD, and normal skin. In psoriatic skin, the numbers of GM-CSFRalpha and IL-12Rbeta2 mRNA-positive cells were significantly increased compared with acute AD lesions, uninvolved skin, and normal control skin (P < .01). CONCLUSIONS: These results demonstrate that acute AD is associated with a high expression of IL-4Ralpha, whereas IL-5Ralpha and GM-CSFRalpha mRNA are predominantly increased in chronic AD and to lesser extent in acute lesions. These findings support the biphasic role of IL-4, IL-5, and GM-CSF in the pathophysiology of AD.

Adult↗
PubMed1998

A randomized, vehicle-controlled trial of tacrolimus ointment for treatment of atopic dermatitis in children. Pediatric Tacrolimus Study Group.

BACKGROUND: A topical formulation of tacrolimus, an immunosuppressant currently marketed for the prevention of rejection after solid organ transplant, is a potential therapeutic agent for atopic dermatitis. OBJECTIVE: We sought to determine the safety and efficacy of tacrolimus ointment in pediatric patients with moderate-to-severe atopic dermatitis. METHODS: In this double-blind, vehicle-controlled multicenter trial, children ages 7 to 16 years were treated with twice daily application of tacrolimus ointment at 1 of 3 concentrations (0.03% [n = 43], 0.1% [n = 49], or 0.3% [n = 44]) or vehicle (n = 44) for up to 22 days, with a 2-week follow-up period. RESULTS: The Physician's Global Evaluation of clinical response showed that 69% (95% confidence interval: 53-82) of patients in the 0.03% tacrolimus ointment group, 67% (95% confidence interval: 52-81) in the 0.1% tacrolimus ointment group, and 70% (95% confidence interval: 54-83) in the 0.3% tacrolimus ointment group, compared with 38% (95% confidence interval: 24-54) in the vehicle group, had a marked to excellent (> or =75%) improvement or clearing of their atopic dermatitis (P =.005, .007, and .004, respectively for the 3 tacrolimus groups compared with the vehicle group). The mean percent improvement for a modified Eczema Area and Severity Index at end of treatment for each of the 3 tacrolimus groups (0.03%, 72%; 0.1%, 77%: and 0.3%, 81%) was significantly better than that of the vehicle group (26%; P <.001). The median percent reduction in pruritus was significantly greater for tacrolimus-treated patients (74% to 89%) than for vehicle-treated patients (51%, P = .027). No serious systemic adverse events were noted, and systemic absorption was minimal. CONCLUSION: Tacrolimus ointment appears to be safe and effective in children with atopic dermatitis.

Administration, Topical↗
PubMed1998

Association of increased CD4+ T-cell infiltration with increased IL-16 gene expression in atopic dermatitis.

BACKGROUND: The mechanisms involved in the initiation and the maintenance of skin inflammation in atopic dermatitis (AD) are poorly understood. Previous studies have demonstrated increased numbers of infiltrating CD4+ T cells in acute lesions compared with normal control skin. IL-16 is a cytokine that has selective chemotactic activity for CD4+ cells. OBJECTIVE: We sought to examine whether IL-16 expression might be upregulated in acute versus chronic AD. METHODS: We investigated the expression of IL-16 mRNA in skin biopsy specimens from acute and chronic skin lesions, as well as from the uninvolved skin of patients with AD and normal skin. Cryostat sections from 4% paraformaldehyde-fixed skin biopsy specimens were processed for in situ hybridization by using cRNA coding for IL-16 mRNA. Numbers of infiltrating CD4+ and CD8+ cells were also determined by immunocytochemistry. RESULTS: There were positive signals for IL-16 mRNA both in the basal layer of the epidermis and in the dermis of AD skin biopsy specimens from all subjects studied. The numbers of epidermal and dermal IL-16 mRNA+ cells were significantly increased in acute skin lesions compared with chronic (P <.01) and uninvolved (P <.001) skin lesions and compared with normal skin (P <.001). The number of CD4+ cells was significantly increased in acute skin lesions compared with chronic (P <.01) skin lesions and uninvolved skin (P <.01) and compared with normal skin (P <.01). Significant correlations were found between the numbers of CD4+ cells and the numbers of epidermal (r = 0.82, P <.001) and dermal (r = 0.71, P <.001) IL-16 mRNA+ cells. CONCLUSION: The results demonstrate that upregulation of IL-16 mRNA expression in acute AD is associated with increased numbers of CD4+ cells, suggesting that IL-16 may play a role in the initiation of skin inflammation, presumably through recruitment of CD4+ cells.

Biopsy↗
PubMed1997

Laparoscopic fundoplication to enhance pulmonary function in children with severe reactive airway disease and gastroesophageal reflux disease.

BACKGROUND: The relationship between severe reactive airway disease (RAD) and gastroesophageal reflux disease (GERD) has been noted but the relationship is poorly understood. This study reports our experience with laparoscopic fundoplication and its effect on the pulmonary status of children with severe steroid-dependent reactive airway disease. METHODS: Fifty-six patients with severe steroid-dependent RAD and medically refractory GERD underwent laparoscopic Nissen fundoplications. Mean age was 7 years and mean weight was 20 kg. All patients had the procedure completed successfully laparoscopically with an average operative time of 62 min. Average hospital stay was 1.6 days. RESULTS: Forty-eight of 56 patients noted significant improvement in their respiratory symptoms in the first week. Fifty of 56 patients have been weaned off their oral steroids and four others have had a greater than 50% decrease in their dose. Sixteen patients had a documented increase in their FEV1 in the initial postoperative period (avg. 26%). CONCLUSION: Patients with steroid-dependent RAD and GERD refractory to medical management show improvement in their respiratory status following fundoplication and the majority can be weaned off of their oral steroids. Laparoscopic techniques allow this procedure to be performed safely even in this high-risk group of patients.

Adolescent↗
PubMed1997

Advances in the understanding and treatment of atopic dermatitis.

Atopic dermatitis is the most common chronic skin disease of young children and is frequently associated with asthma and allergies. Th2-type cytokine secreting T cells expressing the cutaneous lymphocyte-associated antigen play a central role in the induction of local IgE responses and recruitment of eosinophils in this disease. Chronic inflammation in atopic dermatitis likely involves a number of interdependent factors, including repeated or persistent exposure to allergens, which can lead to Th2-cell expansion. In addition, exotoxins secreted by Staphylococcus aureus acting as both superantigens and allergens can contribute to persistent inflammation or exacerbations of atopic dermatitis. Treatment of atopic dermatitis with topical agents such as tacrolimus ointment and phosphodiesterase-4 inhibitors offers new approaches directed at correction of the immune dysfunction associated with this disease.

Adjuvants, Immunologic↗
PubMed1996

In vivo expression of IL-12 and IL-13 in atopic dermatitis.

Previous studies in atopic dermatitis (AD) have shown that acute and chronic skin lesions are associated with a TH2-type profile of cytokine expression. IL-12 and IL-13 are recently described cytokines, which possess TH1-and TH2-like actions, respectively. We have used the technique of in situ hybridization to examine the expression of IL-12 and IL-13 messenger RNA in skin biopsy specimens of acute and chronic skin lesions and uninvolved skin from patients with AD. When compared with normal control skin, the acute and chronic skin lesions and unaffected skin from patients with AD had significantly greater numbers of cells that were positive for IL-13 mRNA (p < 0.05). Acute AD skin lesions expressed a higher number of positive cells than those observed in chronic AD skin lesions (p < 0.05) or psoriasis skin lesions (p < 0.05) There was a significant increase in the numbers of IL-12 mRNA-positive cells in chronic skin lesions compared with acute lesions and uninvolved skin from patients with AD (p < 0.05). These data demonstrate that acute AD skin lesions are associated with an increased expression of IL-13 mRNA. In contrast, the relative increase in IL-12 mRNA in chronic AD skin lesions suggests a possible role for IL-12-producing cells in modulating chronic inflammation.

Acute Disease↗