Algorithms for Treating Dyslipidemia in Youth.

PURPOSE OF REVIEW: The goal of this article is to review algorithms for treating dyslipidemia in youth, discuss pitfalls, propose enhanced algorithms to address pitfalls, and consider future directions. RECENT FINDINGS: The presence of modifiable and non-modifiable cardiovascular disease (CVD) risk factors during childhood is associated with CVD-related events in adulthood. Recent data has shown that childhood initiation of statin therapy in youth < 18 years of age with familial hypercholesterolemia reduces the risk of adult CVD. However, pediatric dyslipidemia remains undertreated in part due to a lack of primary health care providers with adequate understanding of screening guidelines and pediatric lipidologists with experience in treatment and follow-up of this unique population. Management algorithms have been published by the National Heart, Lung, and Blood Institute and American Heart Association as tools to empower clinicians to manage dyslipidemia. We propose enhanced algorithms, which incorporate recently approved pharmacotherapy to address the management gaps. Future algorithms based upon clinical risk scores may enhance treatment and improve outcomes. Algorithms for dyslipidemia management which target youth < 18 years of age are tools which empower clinicians to manage dyslipidemia in this unique population. Enhanced algorithms may help address pitfalls. We acknowledge the need for further risk assessment tools in pediatrics for tailored dyslipidemia management.

Post-adolescent acne in women: more common and more clinical considerations.

Current evidence suggests that post-adolescent acne in women is on the rise. Acne in this subgroup of patients commonly follows a specific pattern that can often be treatment resistant and/or prone to relapse, including after oral isotretinoin therapy. With a plethora of medications to choose from for acne treatment, many of which have been used in the past by patients without success, dermatology practitioners often find oral contraceptives and spironolactone to be of benefit in otherwise healthy adult females. Also, some of these patients may have concurrent hormonal anomalies such as polycystic ovarian syndrome or other underlying endocrine disorders, which should also be appropriately worked up by the clinician and managed accordingly. This article reviews some of the underlying pathophysiological factors, available treatment options, and screening guidelines to assist clinicians in the management of acne in adult females.

Laser and light-based therapies for acne vulgaris: a current guide based on available data.

There are some patients that, despite their continued use of optimized topical and systemic medication and skin care regimens, exhibit at least partial persistence of acne vulgaris (AV) lesions that is bothersome and treatment-resistant to pharmacologic approaches. Additionally, professional, public and governmental concern regarding "antibiotic resistance" has led to interest in therapeutic alternatives other than antibiotics. These challenges drive research into non-pharmacologic approaches to AV treatment, including laser and light-based approaches.

Topical antibiotics: therapeutic value or ecologic mischief?

Based on antibiotic prescribing data from 2003, dermatologists account annually for 8-9 million prescriptions for oral antibiotics, and 3-4 million prescriptions for topical antibiotics. Overall, much of the emphasis on concerns related to emergence of clinically significant antibiotic-resistant bacterial strains focuses on use of systemic antibiotics, however, topical antibiotic use may also have potential implications. The following article discusses the perspectives of the authors related to the potential therapeutic benefits and ecologic implications ("ecologic mischief") of topical antibiotic therapy for specific indications encountered in ambulatory dermatology practice.

Inter- and intra-group variability in perceptions of behavior among Asian Americans and European Americans.

Between-group and within-group differences in perceptions of behavior were examined among 74 Asian Americans and 111 European Americans. Participants rated videotaped interactions of Asian American mothers and daughters. Asian Americans, and a more homogeneous sample of Chinese Americans, perceived less maternal control and more reciprocity than did European Americans. Intra-cultural variations in perceptions were also evident, as within-group analyses revealed differences in perceptions based on the generational status of Asian Americans and the degree of multicultural experience of European Americans. Overall, findings suggest that perceptions of behavior are shaped as much by within-group differences in familiarity and experience with the target culture as by between-group differences in ethnicity. Implications for theories of child socialization, multicultural counseling, and observational research are discussed.

Topical pimecrolimus 1% cream in the treatment of seborrheic dermatitis.

Seborrheic dermatitis is a multifactorial skin disease characterized by a chronic course with periods of exacerbation and remission. Although topical corticosteroids have been the mainstay of treatment, alternative therapies are often needed to avoid protracted use of topical corticosteroid therapy in order to avert side effects and to sustain control of the disorder. Topical pimecrolimus, a calcinuerin inhibitor, is a safe alternative for seborrheic dermatitis and is more ideal for long-term use. More specifically, topical pimecrolimus not only has an attractive safety profile with no risk of many of the potential side effects seen with topical corticosteroids, but also has favorable efficacy data, including more data on long-term use. This is a review of literature evaluating the efficacy and safety profile of topical pimecrolimus 1% cream for the treatment of seborrheic dermatitis.

Treatment of Cutaneous Lupus Erythematosus: Review and Assessment of Treatment Benefits Based on Oxford Centre for Evidence-based Medicine Criteria.

The treatment of cutaneous lupus erythematosus is centered upon formulating a regimen of topical and systemic therapies designed to reduce disease activity and minimize cosmetic damage. Sun avoidance and sunscreen are important preventative measures proven to minimize cutaneous lupus erythematosus exacerbations. Limited disease is typically managed with topical corticosteroids or calcineurin inhibitors. Antimalarial therapy is the gold standard of systemic therapy. Many other treatments have been studied in patients with recalcitrant cutaneous lupus erythematosus, and their use must be evaluated based on individual risk-benefit concerns. R-salbutamol and pulsed dye laser therapy have proven to be effective topical alternatives. Additional systemic agents include retinoids, immunosuppressants, immunomodulators, biologics, and other experimental therapies with novel modes of action. According to the Oxford Centre for Evidence-based Medicine criteria for evaluating the strength of evidence supporting an individual treatment measure, no therapy for cutaneous lupus erythematosus has achieved Level 1 status. This demonstrates the need for randomized, controlled trials and systematic reviews of all cutaneous lupus erythematosus interventions in order to meet increasing standards and demand for evidence-based practice.

Oral Spironolactone in Post-teenage Female Patients with Acne Vulgaris: Practical Considerations for the Clinician Based on Current Data and Clinical Experience.

Oral spironolactone has been used for over two decades in the dermatological setting. Although it is not generally considered a primary option in the management of female patients with acne vulgaris, the increase in office visits by post-teenage women with acne vulgaris has recently placed a spotlight on the use of this agent in this subgroup of patients. This article reviews the literature focusing on the use of oral spironolactone in this subset of women with acne vulgaris, including discussions of the recommended starting dose, expected response time, adjustments in therapy, potential adverse effects, and patient monitoring.

Status report on the management of dermatofibrosarcoma protuberans: is there a viable role for the use of imatinib mesylate? In which cases may it be therapeutically helpful and in which cases not?

Dermatofibrosarcoma protuberans (DFSP) is an uncommon cutaneous neoplasm with intermediate- to low-grade malignancy, but can be a surgical challenge. DFSP is characterized by a storiform proliferation of bland-appearing cells that diffusely infiltrate the dermis. Due to these characteristics, it has a high potential for wide and deep extensions into the deep dermis. Although the majority of DFSPs are cured by Mohs micrographic surgery, tumor size and disfigurement may be a limiting factor for such a procedure. Moreover, even when surgery is utilized, there are cases where positive margins remain, in which case imatinib would be an option, often in combination with surgery. Imatinib can decrease tumor size preoperatively and help to improve postsurgical aesthetic appearance and minimize functional impairment. This article is a review of literature examining the indications for the use of imatinib in DFSP lesions and understanding the pathophysiology behind the treatment.

Drug-provoked psoriasis: is it drug induced or drug aggravated?: understanding pathophysiology and clinical relevance.

Psoriasis is a commonly encountered dermatosis with a variety of internal and external paradoxical factors contributing to the clinical course of the disease. There are several drugs described in the literature that have been associated with the initiation, exacerbation, and aggravation of psoriasis. Understanding the pathophysiology can provide clues to treatment and management of drug-induced and drug-aggravated psoriasis, which may be indistinguishable from idiopathic psoriasis. The clinical manifestations of drug-associated psoriasis can range from plaque-type psoriasis to severe erythroderma, thus warranting astute and sustained clinical observation.

Inhibition of Mer and Axl receptor tyrosine kinases in astrocytoma cells leads to increased apoptosis and improved chemosensitivity.

Astrocytomas account for the majority of malignant brain tumors diagnosed in both adult and pediatric patients. The therapies available to treat these neoplasms are limited, and the prognosis associated with high-grade lesions is extremely poor. Mer (MerTK) and Axl receptor tyrosine kinases (RTK) are expressed at abnormally high levels in a variety of malignancies, and these receptors are known to activate strong antiapoptotic signaling pathways that promote oncogenesis. In this study, we found that Mer and Axl mRNA transcript and protein expression were elevated in astrocytic patient samples and cell lines. shRNA-mediated knockdown of Mer and Axl RTK expression led to an increase in apoptosis in astrocytoma cells. Apoptotic signaling pathways including Akt and extracellular signal-regulated kinase 1/2, which have been shown to be activated in resistant astrocytomas, were downregulated with Mer and Axl inhibition whereas poly(ADP-ribose) polymerase cleavage was increased. Furthermore, Mer and Axl shRNA knockdown led to a profound decrease of astrocytoma cell proliferation in soft agar and a significant increase in chemosensitivity in response to temozolomide, carboplatin, and vincristine treatment. Our results suggest Mer and Axl RTK inhibition as a novel method to improve apoptotic response and chemosensitivity in astrocytoma and provide support for these oncogenes as attractive biological targets for astrocytoma drug development.

Skin cancer in asians: part 2: melanoma.

The Asian population in the United States is expected to increase in the next 50 years. Concurrently, there is an overall rise in the incidence of melanoma. It is therefore crucial to obtain a better understanding of this deadly skin cancer in this minority population, as little information is currently available and prognosis remains poor. Through a review of the literature, this paper explores melanoma in the Asian population, including the most common subtype encountered, prognosis, theories on pathogenesis, and molecular biology.

Skin cancer in asians: part 1: nonmelanoma skin cancer.

Since the 1960s, basal cell carcinoma and squamous cell carcinoma among the Caucasian population have increased 3 to 8 percent annually. Although Asians display relative protection from basal cell carcinoma and squamous cell carcinoma, incidence rates of these nonmelanoma skin cancers have been increasing over the past three decades. With changing demographics and a steady rise in the minority population in the United States, there is an increased need for further studies of cutaneous malignancies within Asian and other ethnic populations. This article reviews nonmelanoma skin cancers in the Asian population with an insight into contributing factors, such as skin type, occupation, cultural practices, and genetic components.

Mer tyrosine kinase (MerTK) promotes macrophage survival following exposure to oxidative stress.

The MerTK plays several important roles in normal macrophage physiology, including regulation of cytokine secretion and clearance of apoptotic cells. Mer signaling in other cell types, including malignant cells that ectopically overexpress the RTK, leads to downstream prosurvival pathway activation. We explored the hypothesis that Mer has a prosurvival role in macrophages exposed to oxidative stress. H(2)O(2) treatment of peritoneal exudate murine macrophages and J774 cells rapidly stimulated Mer phosphorylation in a concentration-dependent manner. Mer phosphorylation was dependent on the ligand Gas6, as treatment with warfarin or MerFc (a fusion protein of the extracellular domain of Mer and the Fc portion of human Ig), inhibitors of Gas6 activity, blocked H(2)O(2)-mediated activation of Mer. Antiapoptotic signals including pAkt and pErk 1/2 were increased dramatically (threefold and 4.5-fold, respectively) in WT Mer-positive macrophages compared with Mer KO macrophages stimulated with H(2)O(2). In a consistent manner, Mer expression led to decreased cleavage of proapoptotic indicators PARP and Caspase-3. Furthermore, Mer provided up to twofold enhanced cellular survival to primary macrophages exposed to H(2)O(2). These data represent the first report of Mer activation in response to oxidative stress and demonstrate the ability of Mer RTK to promote macrophage survival in disease states that involve an oxidative stress environment.