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Biomedical subjects

Jon M Hanifin

Publications and source records attributed to Jon M Hanifin.

17 recordsLinked to original sources

Multiple diagnostic techniques identify previously vaccinated individuals with protective immunity against monkeypox.

Approximately 50% of the US population received smallpox vaccinations before routine immunization ceased in 1972 for civilians and in 1990 for military personnel. Several studies have shown long-term immunity after smallpox vaccination, but skepticism remains as to whether this will translate into full protection against the onset of orthopoxvirus-induced disease. The US monkeypox outbreak of 2003 provided the opportunity to examine this issue. Using independent and internally validated diagnostic approaches with >or=95% sensitivity and >or=90% specificity for detecting clinical monkeypox infection, we identified three previously unreported cases of monkeypox in preimmune individuals at 13, 29 and 48 years after smallpox vaccination. These individuals were unaware that they had been infected because they were spared any recognizable disease symptoms. Together, this shows that the US monkeypox outbreak was larger than previously realized and, more importantly, shows that cross-protective antiviral immunity against West African monkeypox can potentially be maintained for decades after smallpox vaccination.

Animals↗

Atopic dermatitis.

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Dermatitis, Atopic↗

Efficacy and safety of tacrolimus ointment treatment for up to 4 years in patients with atopic dermatitis.

OBJECTIVE: This study was designed to evaluate the long-term safety and efficacy of 0.1% tacrolimus ointment in adult and pediatric patients with atopic dermatitis (AD). METHODS: A total of 408 adult and 391 pediatric patients with AD who had participated in a previous clinical trial of tacrolimus ointment were enrolled in this long-term, open-label, noncomparative trial. Tacrolimus ointment 0.1% was applied twice daily either intermittently or continuously to the affected areas. Efficacy and safety assessments included percent body surface area affected, Eczema Area and Severity Index score, individual signs of AD, and the incidence of adverse events. RESULTS: A total of 799 patients were evaluated, of whom 300 (37.5%) were followed for more than 3 years (maximum 49 months). Improvements in efficacy parameters were observed within 1 week of treatment and continued for the duration of the study. Common adverse events included skin burning, pruritus, skin infection, skin erythema, flu-like symptoms, and headache. The incidence of adverse events, including cutaneous infections, did not increase with time on study. CONCLUSION: Tacrolimus ointment therapy is a rapidly effective and safe treatment for the management of AD in pediatric and adult patients for up to 4 years.

Adolescent↗

Effective therapy of childhood atopic dermatitis allays food allergy concerns.

BACKGROUND: Roughly one third of children with atopic dermatitis (AD) have IgE-mediated food allergy. Most parents and pediatricians assume foods also cause the eczema, a focus that diverts proper skin therapy and has negative outcomes including nutritional deficiency, costly referrals, and unnecessary testing. This project investigates the relationship between food allergy and AD, both before and after treatment in an established AD population. During an open trial of topical tacrolimus we observed a decrease in parental food allergy concern during good control of their child's eczema. We tested this observation by follow-up interviews and a questionnaire study to compare parental estimates of food allergy concerns after therapy with concerns before beginning the trial. Study subjects were children 11 years old and younger with AD and suspicion of food allergy. AD and food allergy parameters, pre- and post-treatment, were retrospectively assessed by a questionnaire given to the parents. RESULTS: Twenty-three patients were enrolled: 16 had positive food allergy tests (7 RAST and/or 10 skin prick tests) and 30% had a definite history of immediate IgE reactions to foods. Ninety-five percent of parents felt that food allergy exacerbated their child's AD. Treatment durations were 3 to 45 months. Parental concern of food allergy decreased significantly from 7.7 to 4.0 on a 10 point scale (P < .001). Additionally, estimated food reactions decreased by approximately 80% during 1- and 6-month periods (P = .001). CONCLUSIONS: In this selected university-based childhood AD population, nearly all parents were convinced their child had food allergy and further that the food contributed to the AD. The level of concern about food reactions was significantly decreased and the number of food reactions declined during effective topical therapy. This preliminary assessment of parental perceptions suggests that successful, stable therapy of AD reduces perceived food reactions and allays parental concerns about food allergy. Such therapy may encourage parents to refocus on direct skin care as the primary effort in AD therapy. We conclude that the effect of successful AD treatment on food allergy and food allergy concern are of interest and worthy of further study.

Child↗

Cell death-induced activation of epidermal growth factor receptor in keratinocytes: implications for restricting epidermal damage in dermatitis.

Recent findings have implicated Fas/Fas ligand (FasL) in mediating the death of keratinocytes in spongiotic lesions. We asked whether dying keratinocytes could potentially initiate a protective response of the skin to limit the destruction of the epidermis in the spongiotic areas. In addition to apoptosis, treatment of keratinocyte cultures in vitro with FasL triggers a profound phoshorylation of the epidermal growth factor receptor (EGFR) and of its downstream effectors ERK and protein kinase B (PKB/Akt). Using a variety of inhibitors and blocking antibodies, we demonstrated that: (i) apoptosis is required for the generation of the signal(s) leading to the activation of EGFR, ERK, and Akt; (ii) the activation of EGFR, ERK, and Akt by FasL is indeed mediated by its bona fide receptor Fas; (iii) the activation of EGFR is essential for the subsequent activation of ERK and Akt; and (iv) apoptotic keratinocytes secrete soluble EGFR ligands (including amphiregulin) that are processed from membrane-bound proligand forms by metalloproteinase(s). Our findings demonstrate a potential mechanism for the restriction and repair of spongiotic damage in eczemas.

Apoptosis↗

Tacrolimus ointment: utilization patterns in children under age 2 years.

Atopic dermatitis (AD) is a common eczematous skin condition; as many as 10-17 percent of all children are affected, and 35-60 percent of affected patients manifest symptoms manifest during the first year of life. Treatment principles for AD in young children involve conservative measures such as avoidance of hot water and environmental irritants, combined with liberal use of emollients after bathing. Low potency topical corticosteroids (TCS) are the current standard of therapy for AD in young children, reserving mid- and high-potency TCS for severe disease. However, complications of long-term use of TCS include skin atrophy, stria formation, telangiectasia, hypopigmentation, secondary infections, steroid acne, allergic contact dermatitis, and miliaria. The pediatric population is also at increased risk for systemic absorption because of their high ratio of skin surface to body mass. Systemic absorption may result in hypothalamic-pituitary-adrenal axis suppression and ultimately growth retardation. Although most topical and systemic corticosteroids are not approved by the Food and Drug Administration for use in children less than 2 years of age, conservative treatment often fails in this age group and frequently patients are treated with TCS, antibiotics, and antihistamines.

Administration, Cutaneous↗

Smallpox: the basics.

Variola major is the causative agent of smallpox, a severe disease that was arguably one of the most serious human pathogens in recorded history. Humans are the only known reservoir of variola major; no known animal or insect reservoirs have been identified. Thus, after eradication of smallpox through a global immunization effort, this incredibly lethal scourge was eliminated from all corners of the globe. Despite the total eradication of naturally occurring smallpox, there are still stockpiles of smallpox virus maintained in the United States and the former Soviet Union. Unfortunately, it is impossible to know if all smallpox stocks have been accounted for or whether unknown or unreported stocks of smallpox may still exist. In the age of genetic engineering, these viruses could theoretically be modified to increase their virulence to the levels associated with smallpox itself.

Biological Warfare↗

Duration of antiviral immunity after smallpox vaccination.

Although naturally occurring smallpox was eliminated through the efforts of the World Health Organization Global Eradication Program, it remains possible that smallpox could be intentionally released. Here we examine the magnitude and duration of antiviral immunity induced by one or more smallpox vaccinations. We found that more than 90% of volunteers vaccinated 25-75 years ago still maintain substantial humoral or cellular immunity (or both) against vaccinia, the virus used to vaccinate against smallpox. Antiviral antibody responses remained stable between 1-75 years after vaccination, whereas antiviral T-cell responses declined slowly, with a half-life of 8-15 years. If these levels of immunity are considered to be at least partially protective, then the morbidity and mortality associated with an intentional smallpox outbreak would be substantially reduced because of pre-existing immunity in a large number of previously vaccinated individuals.

Adult↗

The safety assessment of fragrance materials.

Safety evaluation of the large number of diverse chemicals used as fragrance ingredients follows a systematic prioritization of data generation and analysis, consideration of exposure and critical analysis of the quality of the available information. In prior publications the research priorities used by the Research Institute for Fragrance Materials (RIFM), and the methods of exposure estimation used by industry have been summarized. This paper provides details of the approach used by the RIFM Expert Panel (REXPAN), to examine the dermal effects, systemic toxicity and environmental consequences of the use of and exposure to fragrance materials, which allow a reliable determination of safe use under intended conditions. The key to the usefulness of this analysis is the grouping of more than 2600 discrete ingredients into classes, based on chemical structures. Research sponsored by RIFM, data supplied by member companies, and relevant published reports from many sources are all considered during hazard characterization. A discussion is provided of REXPAN's decision tree approach to assessing the dermal, systemic and environmental endpoints and the types and quality of data included. This overall process results in well-documented conclusions which are provided to the International Fragrance Association (IFRA) as the basis for consideration of a new or existing Fragrance Material Standard and to industry for appropriate product risk management actions.

Consumer Product Safety↗

Atopic dermatitis and asthma: parallels in the evolution of treatment.

OBJECTIVES: To review epidemiologic correlations between asthma and atopic dermatitis (AD), identify common features in disease pathophysiology, and review steps involved in the development of asthma therapy guidelines to assess the appropriateness of a similar process and approach for AD. METHODS: A 7-member panel representing specialists in dermatology, allergy, asthma, immunology, and pediatrics from around the United States convened to review the current literature and evolving data on AD. Participants presented reviews to the panel on the epidemiology of asthma and AD, the genetic predisposition to allergic disease, the current understanding of the immunopathophysiology of AD, interrelationships between the pathologic pathways of asthma and AD, evolving treatment concepts and options in AD, and the applicability of the asthma treatment model and how it may be adapted for guideline development for AD. Commentary and criticism were recorded for use in document preparation. RESULTS: There are clear epidemiologic parallels in asthma and AD. Importantly, AD frequently is the first manifestation of an atopic diathesis, which occurs in genetically predisposed individuals and also includes asthma and allergic rhinitis. Up to 80% of children with AD will eventually develop allergic rhinitis or asthma later in childhood. This classic "atopic triad" has numerous pathophysiologic elements in common, including cyclic nucleotide regulatory abnormalities, immune cell alterations, and inflammatory mediators and allergic triggers. New therapeutic options that target underlying immune mechanisms are available, and their place among treatments for AD is becoming established. Guidelines of care have been developed for asthma. The panel noted that the National Institutes of Health/National Heart, Lung, and Blood Institute guidelines for diagnosis and management of asthma, first issued in 1991, had a tremendous positive impact on many aspects of asthma treatment. It not only created a heightened awareness that asthma is a disease of chronic inflammation, but it also provided unified approaches for therapy and opened new areas of basic science and clinical research. In addition, the guidelines spurred interactions among physicians of various specialties and stimulated a great quantity of research in asthma therapy. It is anticipated that AD therapy guidelines would have similar positive outcomes. CONCLUSIONS: The panel concluded that, on the basis of current information and evolving therapeutic options, a clear rationale exists to support AD guideline development. The many parallels between AD and asthma suggest that processes and approaches used for the asthma therapy guidelines would be appropriate for AD.

Administration, Topical↗

An overview of atopic dermatitis.

Atopic dermatitis (AD) is an inflammatory disease, characterized by marked pruritus, which typically assumes a chronically relapsing course. Although AD is primarily a childhood disease, 60% to 70% of adults with AD suffer from hand eczema. Caring for patients with AD is time consuming and difficult. Patients and parents need proper education and detailed instructions from nurses and physicians to avoid flares and complications. Recognizing signs of infection and beginning appropriate treatment for them are important. Instruction on corticosteroid therapy as well as use of topical immunomodulators is crucial to effective acute and long-term management of AD.

Adult↗

Considerations for testing irritancy, allergy, and photoreactivity in fragrance safety evaluations.

The aims of the Research Institute for Fragrance Materials, Inc. (RIFM), an international nonprofit science-based organization established in 1966 by the fragrance industry, include the prevention of adverse cutaneous effects, systemic toxicity, and environmental consequences from fragrance ingredients. This paper gives an overview of the RIFM testing and research program, how priorities are established, and how RIFM's safety evaluation process works.

Allergens↗

Patient and physician perspectives vary on atopic dermatitis.

We compared the written responses of physicians (n=303) and patients (n=961) from a nationwide US survey concerning atopic dermatitis (AD). Physicians, primarily dermatologists, responded to 32 questions, and patients responded to 44 questions about AD and its management. Most physicians and patients were in agreement regarding disease severity, the relative lack of effectiveness of over-the-counter products, concerns about drug adverse effects, and the need for more patient support groups. However, physicians were more concerned about long-term adverse effects than were patients. Additionally, 91% of physicians versus 46% of patients rated prescription medications as "moderately" or "very" effective. Patients were generally pleased with their overall AD-related medical care: 42% were "a lot" or "very" satisfied, while only 8% were dissatisfied. Although physician and patient perceptions sometimes differed, both groups preferred treatments offering greater effectiveness, fewer adverse effects, and greater applicability to the pediatric population.

Adolescent↗