Biomedical subjects

Alan Menter

Publications and source records attributed to Alan Menter.

48 records · Page 3Linked to original sources

PubMed2002

Novel immunoglobulin superfamily gene cluster, mapping to a region of human chromosome 17q25, linked to psoriasis susceptibility.

Chromosome 17q25 harbors a susceptibility locus for psoriasis ( PSORS2). This locus may overlap with loci for atopic dermatitis and rheumatoid arthritis. To further refine the location of PSORS2, we genotyped 242 primarily nuclear families for 15 polymorphic microsatellites mapping to chromosome 17q23-q25. Non-parametric linkage analysis revealed a linkage peak lying close to a novel cluster of genes from the immunoglobulin (Ig) superfamily. This cluster spans >250 kb and harbors five CMRF35-like genes and a sixth inhibitory receptor ( CMRF35H) with three ITIM motifs that is transcribed in the opposite direction from the rest. The Ig domains encoded by these genes are most similar to those of the TREM (triggering receptor expressed selectively in myeloid cells) molecules, NKp44 and the polymeric immunoglobulin receptor. CMRF35-like genes are only expressed in sub-populations of cells of the myeloid lineage. In order to investigate the association of this region with psoriasis, we genotyped the families for 13 novel microsatellites and 19 SNPs from the region of linkage. A maximum NPL of 1.6 ( P=0.05) was obtained within the interval. Two SNP-based haplotypes revealed some evidence for association with psoriasis. One spanned CMRF35H and includes a non-synonymous polymorphism within CMRF35H (R111Q) (TDT P=0.03). The second was a three-locus haplotype lying within the first intron of CMRF35A2 ( TREM5) (TDT P=0.04). The novel markers described here will facilitate additional linkage and association studies between the CMRF35 family and disease.

Adult↗

PubMed2002

Update on botulinum toxin for facial aesthetics.

The use of botulinum toxin has revolutionized the treatment of facial lines with an incomparable safety record over the past 14 years. The most common used injection sites are shown in Fig. 9. With the recent FDA approval for Botox in the treatment of glabellar lines, its use will likely increase dramatically. It is essential that practitioners have a detailed and specific knowledge of the facial and neck musculature to be injected to minimize untoward side effects, especially in the early days of new users' learning curve. The specifics of the dilutions and units per amount used for the various different commercial forms of botulinum toxin types A and B need to be understood fully and standardized together with the potential for antigenicity with the higher protein load of type B. In addition, specific indications for the use of botulinum toxin as adjunctive therapy for specific facial surgical procedures (i.e., blepharoplasty, surgical brow lift, and laser resurfacing) will become better understood. [figure: see text] Finally, even though the anatomy of the facial musculature is well described, individual differences in men and women, in different population groups, and in tissue qualities, such as turgor and elasticity [87], are important factors to be considered before undertaking botulinum toxin injections. It is likely that the use of specific measuring devices, such as digital imaging, will further help define the use of botulinum toxin for different muscle groups and facial aesthetic indications.

Botulinum Toxins, Type A↗

PubMed2002

A randomized, double-blind, placebo-controlled study of clobetasol propionate 0.05% foam in the treatment of nonscalp psoriasis.

BACKGROUND: Topical corticosteroids are the primary treatment for mild to moderate psoriasis. Foam preparations of corticosteroids offer potential cosmetic and pharmacodynamic advantages over cream and ointment vehicles. A clobetasol propionate foam product is as effective as clobetasol propionate solution in the treatment of scalp psoriasis. AIM: To evaluate the safety and efficacy of clobetasol propionate foam in the treatment of psoriasis involving sites other than the scalp. METHODS: Eighty-one subjects with mild to moderate psoriasis were randomized in a 3 : 1 ratio to receive clobetasol propionate foam vs. placebo foam treatment in this double-blind study of psoriasis involving nonscalp sites. The investigator's and subject's global assessment of the response at week 2 (or at the end of treatment) and at week 4 (follow-up) and the severity of erythema, scaling, and plaque thickness were assessed. Safety was assessed from reported adverse events. RESULTS: After 2 weeks of treatment, there was significantly greater improvement with clobetasol propionate foam compared with placebo foam in both investigator's and subject's global assessment of the response (P < 0.0005). The improvement with clobetasol propionate foam was still present at the 4-week follow-up visit. Adverse effects were generally limited to mild to moderate application site reactions. No subjects withdrew because of adverse events. CONCLUSIONS: Clobetasol propionate foam is more effective than placebo in the treatment of nonscalp psoriasis. Twice-daily applications are well tolerated, compliance exceeds 90%, cosmetic characteristics are acceptable, and the medication may eliminate the need for separate scalp and body prescriptions.

Administration, Topical↗

PubMed2002

Cardiocutaneous syndromes and associations.

UNLABELLED: Multiple cardiocutaneous syndromes and associations are described and reviewed with the emphasis on syndromes that are likely first to be recognized by dermatologists, thereby creating awareness of potential significant cardiovascular disease. Multiple lentigines syndrome, the Carney complex, and Marfan syndrome are examples of syndromes with embryologic and genetic overlap between the cardiac and cutaneous systems. An exhaustive, complete listing of every known disorder or syndrome with combined cardiac and cutaneous findings is beyond the scope of this review. However, all the common associations, both acquired and inherited, including connective tissue, autoimmune, infiltrative, and endocrine disorders are discussed. Because of the serious nature of many of the cardiac defects, early recognition of these conditions by dermatologists and appropriate referrals to colleagues is essential; in addition, when appropriate, genetic counseling is recommended for known heritable disorders. LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should be familiar with the embryology of the neural crest, specifically the development of melanocytes and the heart with its vessels, leading to shared abnormalities of the two systems; the major syndromes and associations producing both cutaneous changes, especially of the pigment systems, and cardiovascular abnormalities; the role of the dermatologist in recognizing these changes; and the need to be cognizant and alert in helping screen for associated systemic disease.

Cardiovascular Diseases↗

PubMed2002

Novel therapies for psoriasis.

The T cell-driven immunopathogenesis of psoriasis has been well recognized since cyclosporine first revolutionized the treatment of psoriasis 20 years ago. Almost all investigative and clinical research subsequently, has concentrated on elucidating the specifics of antigen presentation, T cell interaction and the production of specific cytokines. The role of the keratinocyte, previously thought to be the primary target cell in psoriasis pathogenesis, has been relegated to a secondary role and the mechanism of action of systemic methotrexate in psoriasis has been challenged, the primary role of the T lymphocyte is now well known. While psoriasis has traditionally been treated "ab initio" with topical medications (corticosteroids, vitamin D(3), and retinoid derivatives), either singly, in combination, or with ultraviolet B (UVB) or psoralens and ultraviolet A (PUVA) therapy, the role of systemic medications has assumed greater prominence. Thus, three systemic medications currently are approved worldwide for the treatment of moderate to severe forms of psoriasis, namely cyclosporine, methotrexate and acitretin. The first two are likely to give significant clearing (greater than 75%) in the majority of cases, whereas acitretin is significantly less effective as monotherapy, but may approach methotrexate and cyclosporine in efficacy, if combined with PUVA or UVB phototherapy. The main limitations of these three drugs remain organ toxicity, especially hepatic toxicity with methotrexate, hypertension and nephrotoxicity with cyclosporine, and teratogenicity and mucocutaneous toxicity with acitretin. Thus, the need for more specific systemic therapy, targeting the T lymphocyte. This has become the major area of clinical research interest over the past 5 years, with the promise of longer-term disease control (improved remissions) and less organ toxicities. Currently, there are over 15 of these "biologic" drugs in various stages of development and clinical trials, either by the subcutaneous, intramuscular or intravenous route. The three main variables are the rapidity of onset, percentages of improvement and remission rates. Without exception, these new systemic agents appear to be remarkably free of systemic organ toxicities (liver, renal, bone-marrow, etc.), with adverse effects being limited to mild flu-like symptoms with the anticipated increase in infections (e.g., herpes simplex) being either equal to placebo or only marginally increased. Not all these agents under evaluation give clinical responses equal to methotrexate or cyclosporine (75% or greater clearing in 75% of cases). In addition, response rates may be slower with some therapies versus others. However, the need for intermittent administration even by the injectable route, longer remissions, lack of systemic organ toxicities and the potential for safer usage in females of child-bearing age, make a compelling argument for widespread acceptance by both patients and the dermatological community. Other modalities under clinical evaluation include vitamin D and retinoid drugs, topically and systemically, with effects on nuclear receptors, as well as more specific wavelengths (308 to 311 nm) of UVB phototherapy with application for more localized forms of psoriasis. For the 2 to 3% of the worldwide population of patients with psoriasis the future has never looked brighter.

Adrenal Cortex Hormones↗

PubMed2002

Effective treatment of actinic keratosis with 0.5% fluorouracil cream for 1, 2, or 4 weeks.

New therapeutic options would benefit patients with actinic keratosis (AK), a precancerous condition that is a significant health concern. The efficacy and safety of a microsphere-based formulation of 0.5% fluorouracil cream were evaluated in a randomized, double-blind, multicenter, parallel-group study. Patients (N= 177) were randomized to receive 0.5% fluorouracil or vehicle once daily for 1, 2, or 4 weeks. Efficacy was assessed by lesion counts and clearance. Safety was evaluated by monitoring adverse events, including facial irritation. Significant improvements were seen from baseline to posttreatment follow-up in all efficacy variables for all fluorouracil regimens compared with vehicle. Patients treated for one week experienced significant improvements compared with vehicle, although efficacy increased with increasing treatment duration. Most patients experienced mild to moderate facial irritation of predictable onset and duration. Once-daily administration of 0.5% fluorouracil cream for 1, 2, or 4 weeks is safe and effective for the treatment of AKs.

Administration, Topical↗

PubMedDate not supplied

Changing paradigms in dermatology: nuclear hormone receptors.

Nuclear hormone receptors (NHRs) are a family of proteins that function similarly as nuclear transcription factors. The NHR family includes glucocorticoid receptors, retinoic acid and retinoid receptors, vitamin D receptors, thyroxin receptors, and peroxisome proliferator activated receptors. These proteins are targets for some of the most commonly prescribed medications in dermatology, including corticosteroids, retinoids, and vitamin D analogues, all of which have limiting side effects. Advances in this field have led to better understanding of the mechanisms of NHR therapeutic and toxic effects, receptor subtypes, tissue distribution, and interaction with other molecules. New generations of more specific NHR ligands designed to increase therapeutic efficacy and limit adverse effects have dramatically expanded the clinical application of NHR-targeting drugs. The current understanding of NHRs and future directions for NHR ligands in dermatology are discussed.

Adrenal Cortex Hormones↗

PubMedDate not supplied

Changing paradigms in dermatology: tumor necrosis factor alpha (TNF-alpha) blockade in psoriasis and psoriatic arthritis.

Psoriasis is an inflammatory T cell-mediated disease characterized by epidermal hyperplasia and parakeratosis, resulting in lesional areas of thick and scaling skin. Elevated levels of proinflammatory cytokines, including TNF-alpha, are found in psoriatic lesions. TNF-alpha has many effects in producing an inflammatory response such as stimulating production of pro-inflammatory molecules (eg, IL-1, IL-6, IL-8, NF-kappaB) and adhesion molecules (eg, ICAM-1, P-selectin, E-selectin). As such, TNF-alpha is a target for immunotherapy in the treatment of psoriasis and psoriatic arthritis. The role of TNF-alpha in the pathogenesis of psoriasis is reviewed, along with clinical trials demonstrating the efficacy of new anti-TNF-alpha immunobiologics in the treatment of psoriasis and psoriatic arthritis.

Arthritis, Psoriatic↗

PubMedDate not supplied

PsEma--a hitherto unnamed dermatologic entity with clinical features of both psoriasis and eczema.

INTRODUCTION: Recent advances in molecular biology have helped establish differences between psoriasis and a group of inflammatory skin disorders commonly referred to as eczema. The authors have observed significant overlap between these two conditions such that a distinction between them may not always be made, even with histologic examination of skin biopsy specimens. OBJECTIVE: To determine how frequently psoriasis patients present features of both psoriasis and eczema. METHODS: The authors conducted a prospective analysis of 100 consecutive psoriasis patients in their clinic. RESULTS: The authors found that 20% could be diagnosed as "intermediate," having lesions with characteristics of both psoriasis and eczema, or a personal history of both. The authors suggest naming this category of inflammatory dermatosis "PsEma"--an overlap condition in which the clinical, histologic, molecular, biologic, and therapeutic responses show characteristics of both psoriasis and eczema.

Diagnosis, Differential↗

PubMedDate not supplied

Impact of efalizumab on psoriasis-specific patient-reported outcomes. Results from three randomized, placebo-controlled clinical trials of moderate to severe plaque psoriasis.

The objective of this study was to document the disease burden associated with moderate to severe plaque psoriasis, and assess the impact of efalizumab psoriasis treatment in improving patient-reported outcomes. This included analysis of patient-reported dermatology-related quality of life (DRQL) and psoriasis symptom scores among patients with moderate to severe psoriasis participating in three phase III, randomized, double-blinded, parallel-group, placebo-controlled, multi-center clinical trials conducted to evaluate the efficacy and safety of efalizumab. A total of 1,242 patients with moderate to severe psoriasis treated either with efalizumab 1.0 mg/kg/wk or placebo were followed for 12 weeks. DRQL and psoriasis symptom severity were assessed at baseline (pre-treatment) and at the end of the first treatment phase (12 weeks). DRQL was measured using the Dermatology Life Quality Index (DLQI). Symptoms were measured using the Psoriasis Symptom Assessment (PSA) and an Itch scale. Disease burden was assessed at baseline by examining responses to individual questions of the DLQI, PSA, and Itch patient-reported outcome measures. The impact of treatment on disease burden was assessed over a 12-week double-blind study period by comparing changes in DLQI, PSA, and Itch scale scores between the active treatment and placebo groups. Patient-reported outcomes were also assessed during a 12-week extended treatment phase. Prior to treatment, the responses to DLQI and PSA items revealed significant disease burden. Greater than 90% of patients reported being embarrassed or self conscious because of their skin, 53% reported that their skin prevented them from working or studying. and 98% reported that scaling and itching was bothersome. Compared to placebo-treated patients, efalizumab-treated patients showed significant improvement in patient-reported outcomes, reducing the limitations and burden associated with moderate to severe psoriasis within each of the three studies, as measured by DLQI (p<0.001), PSA-Severity (p<0.001), PSA-Frequency (p<0.001), and Itch (p<0.001) scores. Across all measures, the proportion of patients that improved on both statistical and clinical criteria for meaningful improvement was at least twofold greater among efalizumab-treated patients than in placebo-treated patients. The benefit of efalizumab was maintained over the course of an additional 12 weeks during an extended treatment phase. In conclusion, patients with moderate to severe plaque psoriasis reported significant DRQL burden and symptom severity at baseline, but efalizumab significantly improved patient-reported DRQL and reduced the frequency and severity of psoriasis symptoms during 12-week double-blind and 12-week extended treatment periods.

Adolescent↗

PubMedDate not supplied

Rationale for the use of topical corticosteroids in melasma.

Corticosteroids have been combined with other agents in the treatment of melasma for years. In early studies by Kligman and Willis, topical dexamethasone as monotherapy produced little depigmentation even after 3 months of therapy. A significant concern is that topical corticosteroids used alone in this setting, especially on the face, may result in epidermal atrophy, telangiectasia, rosacea-like erythemas, acne, and perioral dermatitis. Topical corticosteroids, however, including low-potency fluocinolone acetonide, also exert an anti-metabolic effect, resulting in decreased epidermal turnover, and, thus, may produce a mild depigmenting effect. When used in combination with tretinoin and hydroquinone in the treatment of melasma, fluocinolone acetonide 0.01% suppresses biosynthetic and secretory functions of melanocytes, and thus melanin production, leading to early response in melasma, synergy among the three agents, and no significant side effects over an 8-week period.

Administration, Topical↗

PubMedDate not supplied

A large 12-month extension study of an 8-week trial to evaluate the safety and efficacy of triple combination (TC) cream in melasma patients previously treated with TC cream or one of its dyads.

This was a 12-month extension of a randomized, investigator-blinded, multicenter, 8-week trial with triple combination (TC) cream in facial melasma. A total of 585 patients were enrolled in the study and 569 patients received study medication. Three hundred eighty-nine patients completed 6 months of treatment and 327 patients completed 12 months of treatment. TC cream demonstrated a favorable safety profile: only 14 patients (2.5%) discontinued the study due to treatment-related adverse events (AEs). The 2 cases of skin atrophy were mild and did not lead to withdrawal. From the 23 cases of mild telangiectasia, only 2 resulted in discontinuation. All others were transient. Results confirmed those of a previous smaller study, with both physicians and patients reporting clinically significant improvements in melasma. By month 12, 80% of patients had lesions completely cleared or nearly cleared. Once daily application of TC cream applied intermittently over a long period is a safe, tolerable, and effective treatment for moderate to severe melasma of the face.

Administration, Topical↗