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Biomedical subjects

Sarah Boyce

Publications and source records attributed to Sarah Boyce.

5 recordsLinked to original sources

Fibroblast growth factor 21 prevents catecholaminergic arrhythmias in a mouse model of PKP2 arrhythmogenic cardiomyopathy.

BACKGROUND: Pathogenic variants in plakophilin-2 (PKP2) cause arrhythmogenic cardiomyopathy (ACM) with intracellular calcium dysregulation as a major component of its arrhythmia phenotype. Recent adeno-associated virus (AAV)-based PKP2 gene therapy has shown promising results in a few different PKP2-associated ACM models. Fibroblast growth factor 21 (FGF21) has multiple cardioprotective effects and has recently emerged as a promising therapeutic agent for cardiovascular disease. OBJECTIVE: This study aimed to assess the efficacy and impact on calcium regulation of a novel AAV serotype 8 (AAV8)-based FGF21 gene therapy on adult cardiac-specific, tamoxifen-activated PKP2 knockout (PKP2-cKO) mice. METHODS: Experiments were performed using a PKP2-cKO murine model. AAV8-FGF21 was delivered to adult mice by a single tail vein injection 7 days before tamoxifen-activated PKP2-cKO. Cardiac functions were monitored using echocardiography and electrocardiography. Intracellular calcium transients were investigated in acute isolated adult mouse cardiomyocytes, and calcium fluorescent signals were acquired using the IonOptix system. RESULTS: Loss of PKP2 expression caused cardiac mechanical dysfunction and proarrhythmic phenotype in adult mouse models. AAV-mediated delivery of FGF21 mitigated the progression of biventricular structural changes, decreased the occurrence of adrenergic arrhythmias, and rescued intracellular calcium imbalance in the setting of PKP2 haploinsufficiency. In contrast, acute in vitro FGF21 treatment for 1 hour had no effect on intracellular calcium transients. CONCLUSION: These beneficial effects of AAV8-FGF21 on the PKP2-ACM phenotype suggest a therapeutic landscape for various targeted cardiomyopathies.

Animals↗

Randomized, controlled surgical trial of preoperative tumor curettage of basal cell carcinoma in Mohs micrographic surgery.

BACKGROUND: The use of preoperative tumor curettage in Mohs micrographic surgery has never been prospectively systematically assessed. OBJECTIVE: To assess the utility of preoperative tumor curettage in Mohs micrographic surgery for primary or recurrent, well-defined basal cell carcinoma less than 2 cm in diameter located on the head or neck. METHODS: Patients were randomized to either preoperative tumor curettage or control group and were compared in terms of percent surface area increase from tumor surface area to wound surface area, absolute surface area increase, number of tissue layers removed, types of repairs performed, and postoperative complications. Multivariate analysis was performed to see if tumor location, appearance (exophytic or flat), or histology affected any of the above. RESULTS: The preoperative tumor curettage group had a 399% (95% confidence interval [CI] 346-452) mean surface area increase from tumor to wound surface area versus 263% (95% CI 216-311) for control group (P=.0002). The preoperative tumor curettage group had a mean absolute surface area increase of 1.78 cm2 (95% CI 1.57-1.99) versus 1.40 cm2 (95% CI 1.15-1.65) for control group (P=.02). The preoperative tumor curettage group had fewer tissue layers removed (P=.3). Preoperative tumor curettage had no effect on types of repairs performed or number or type of postoperative complications. Tumor appearance and histology had no effect on any of the above end points. CONCLUSION: Preoperative tumor curettage was associated with significantly greater percent surface area increase and absolute surface area increase from tumor surface area to wound surface area. This difference did not affect type of repair performed or postoperative complications.

Basal Cell Carcinoma↗

Paraneoplastic dermatoses.

Skin manifestations of systemic disease and malignancy are protean. The recognition of a potentially paraneoplastic dermatosis as such must prompt an investigation for occult malignancy. Lack of familiarity with cutaneous clues of internal malignancy may delay diagnosis and treatment of cancer. It is important to consider a paraneoplastic process in the differential diagnosis of a number of eruptive and treatment-resistant dermatoses. These dermatoses may be the first sign of an occult neoplasm. Their recognition may assist in cancer detection and the swift induction of appropriate therapy.

Diagnosis, Differential↗

CO2 laser treatment of epidermal nevi: long-term success.

BACKGROUND: Epidermal nevi have been notoriously difficult to treat due to their large size and often conspicuous location. Variable results have been obtained with different laser treatments, and scarring and/or incomplete removal is typical after excisional or other destructive modalities. OBJECTIVE: To outline the successful use of a short-pulsed CO2 laser in the long-term eradication of epidermal nevi in three patients. METHODS: Three females (ages 15-19) presented with extensive grouped verrucous papules and plaques on the face, trunk, and extremities. A pulsed CO2 laser was used to vaporize the lesions using a 500 mJ pulse energy, 3 mm spotsize, and 7 watts of power. RESULTS: All lesions healed without incident. No lesional recurrence was observed 10 to 13 months after treatment except in one small area on the ankle in one patient. CONCLUSIONS: Carbon dioxide laser vaporization of epidermal nevi provides good clinical effect and offers unique advantages for the treatment of these lesions, including effective intraoperative hemostasis with excellent lesional visualization. It is also possible to treat widespread areas in one laser treatment session. While the results of this series clearly show the benefit of CO2 laser treatment, epidermal nevi may not always respond so favorably, due in part to the variability in their depths of involvement.

Adolescent↗

Treatment of atopic dermatitis and psoriasis vulgaris with bupropion-SR: a pilot study.

OBJECTIVE: To determine whether the antidepressant bupropion may be useful in treating atopic dermatitis and psoriasis in nondepressed patients. METHOD: Ten nondepressed subjects with atopic dermatitis and 10 with psoriasis completed a single-track, open-label treatment protocol with bupropion-SR in doses of 150 mg/day and 300 mg/day, administered sequentially for 3 weeks each, followed by a 3-week wash-out. Treatment response was assessed at the end of each 3-week period. RESULTS: Six of the 10 subjects with atopic dermatitis showed a reduction in affected body surface area by the end of 6 weeks of bupropion treatment, with affected area increasing toward the prestudy baseline in all responders following bupropion discontinuation-a highly significant treatment effect (p =.0003). Of the 10 subjects having psoriasis, improvement over baseline after 6 weeks of treatment was seen in eight subjects, with coverage increasing toward the prestudy baseline in the responders following bupropion discontinuation (p =.001). Average reduction in affected area in the responders at week 6 of treatment was approximately 50% in both groups. CONCLUSIONS: The generally good tolerability and relative safety of bupropion-SR makes a trial of this agent worthwhile in patients with atopic dermatitis or psoriasis who have failed treatment with more conventional medications. Normalization by bupropion of potentially causative neuroendocrine, immunologic, or catecholaminergic abnormalities in both of these dermatologic disorders is a possible mechanism of action for the observed salutary effects of this drug on our subjects' skin disease.

Adult↗