Effectiveness and safety of 0.5% timolol solution in the treatment of pyogenic granuloma: A randomized, double-blind and placebo-controlled study.

Introduction Pyogenic granulomas are benign vascular lesions of the skin and mucosa which are often a source of concern because of their recurrent bleeding even with minimal trauma. Current treatment for pyogenic granuloma is ablative; no medical therapy is standardized to date. Timolol, due to its vasoconstrictive effect, vascular growth factor inhibition and apoptosis promotion properties, is a potential therapeutic option. Objectives: To assess the effectiveness and safety of topical timolol in the treatment of pyogenic granulomas. Methods A two-centre, double-blind and placebo-controlled trial (Registration CTRI/2019/04/018581) was conducted. Patients of either sex were recruited with pyogenic granuloma lesions of less than eight weeks duration. Topical treatment with 0.5% timolol or matching glycerin placebo was continued for six weeks. Changes in color, size, bleeding tendency, physicians' and patients' global assessments and adverse events were assessed. Results Forty subjects were randomized between the two groups which were comparable in age, sex, duration of illness and baseline lesion size.Significant improvement was noted with timolol, with color change from first follow-up onwards and lesion size reduction from second follow-up onward. Patients' assessment of bleeding tendency also showed imrovement from the second visit onward. Between-group comparison showed significant difference with respect to percentage reduction in size (timolol 40.9%, placebo 3.4%; P = 0.002). Rescue treatment (electrosurgery) was required in five patients on placebo and in one in the timolol group (P = 0.182). Complete resolution occurred in 2 (10%) patients with timolol and in no patients on placebo (P = 0.231). Limitations: We observed effects of treatment for only six weeks. Conclusion Topical timolol may be a treatment option for early pyogenic granulomas but complete resolution is unlikely in six weeks. Studies of longer duration are required to assess resolution and recurrence rates.

Targeted genetic and molecular therapies in neurofibromatosis - A review of present therapeutic options and a glimpse into the future.

Neurofibromatosis type 1, the most common phakomatoses, can present with a host of signs and symptoms, usually involving the skin and the peripheral nervous system. It is characterized by a mutation in the neurofibromatosis type 1 gene on chromosome 17q11.2 that codes for the protein neurofibromin. Neurofibromin acts as a tumor suppressor gene by inhibiting rat sarcoma (Ras) activity and its deficiency leads to increased Ras activity, cellular proliferation and tumor formation. This review was conducted to analyze the various targeted therapies at the genetic and molecular level employed to manage the tumors and other clinical presentations associated with neurofibromatosis type 1. Twenty-eight studies of treatment modalities for the conditions associated with neurofibromatosis and which involved either targeted gene therapy or molecular level therapies, including the latest advances, were included in this review. Mitogen-activated protein kinase kinase inhibition, mammalian target of Rapamycin inhibition and Tyrosine kinase inhibition, represent some of the newer treatment options in this category. Although there are a number of trials for providing therapeutic options at the genetic and molecular level for the various physical and psychological morbidities associated with neurofibromatosis type 1, most of them are in the preclinical stage. Increased clinical trials of the molecules and gene therapies could significantly help in managing the various chronic and sometimes, life-threatening conditions associated with neurofibromatosis 1 and these will probably represent the preferred treatment direction of the future.

Simple moulage for improving simulation for objective structured clinical examinations in undergraduate dermatology courses.

BACKGROUND: Objective structured clinical examination (OSCE) is being increasingly used as an assessment tool for undergraduate dermatology courses. One of the practical difficulties in conducting OSCEs in dermatology is getting patients with typical skin lesions which can be used for the whole group to ensure uniformity of assessment. We present a study on the use of simple moulage techniques to create uniform and standardized skin lesions for OSCEs in dermatology. METHODS: As a first step, the dermatology faculty in our department chose the clinical conditions which could be covered by using moulages. The main criteria considered were the importance of the condition to the exam blueprint, ease of making and resistance to handling (should not require frequent retouching). Moulages were created on volunteers after taking consent and the same were used in OSCEs s for a group of 5th-year students (N = 102). Difficulty and discrimination indices were compared between the stations using the moulage and the other stations. Qualitative feedback was obtained regarding the same from both the faculty and the students. RESULTS: There was consensus among the faculty and the majority of the students that the lesions were clearly recognizable. As far as other psychometrics were concerned, average difficulty and discrimination of the stations using the moulage were good (average difficulty index-0.78 and average discrimination index-0.68) and compared favorably with the other stations (average difficulty index-0.77 and average discrimination index-0.57). LIMITATIONS: Limited number of stations included, lack of detailed item analysis and lack of feedback from the simulated patients were the main limitations in this study. CONCLUSION: For most common skin conditions creating moulages to simulate the corresponding lesions is an easy procedure and can be an effective tool to standardize dermatology OSCEs for undergraduates, especially in resource-poor settings.

Malignant melanoma: Underlying epigenetic mechanisms.

Although malignant melanoma is not the most common type of skin cancer, it is the most aggressive and fatal type as it can spread out and metastasize progressively. Early diagnosis and interventions lead to improved patient survival. The incidence rate of melanoma is dramatically increasing, with a few newer therapeutic options available. Therefore, establishing a reliable genetic or epigenetic-based diagnostic and prognostic tool is really important. In this review, we highlight the underlying epigenetic mechanisms involved in melanoma. Furthermore, the epigenetic-based therapeutic options will be also discussed. One of the key areas of discussion will be microRNA which is a small, single-stranded RNA molecule that serves as a regulatory element and found to regulate nearly a third of human genes. MicroRNAs play a role in a wide range of diseases including cancer. In malignant cells, it regulates cell proliferation, invasion, and metastasis.