Case Report of Disseminated Adrenal Histoplasmosis and Secondary Adrenal Insufficiency.

Histoplasmosis is a chronic, infectious disease caused by the environmental fungus H. capsulatum, primarily affecting the respiratory system. In immunocompromised patients, histoplasmosis can become severely complicated due to dissemination into various other organ systems. Adrenal insufficiency is an uncommon complication of disseminated histoplasmosis, as its manifestation requires necrotizing granulomatous inflammation of both adrenal glands. We describe a rare case of delayed histoplasmosis in the bilateral adrenal glands and liver of an immunocompromised patient with development of symptoms at 21 years after liver transplant and nine years after renal transplant. In addition, this patient presented with secondary adrenal insufficiency due to long-term use of corticosteroids rather than the typical primary adrenal insufficiency seen in histoplasmosis with adrenal involvement.

Prospective analysis of toxicity in patients treated with strut-adjusted volume implant for early-stage breast cancer.

PURPOSE: We report the toxicity of patients treated with strut-adjusted volume implant (SAVI) for accelerated partial breast irradiation treated at our institution. METHODS AND MATERIALS: Patients treated from January 2013 to July 2015 with SAVI planned for 10 b.i.d. fractions for a total dose of 34 Gy were included. Acute and late toxicities were prospectively collected on patients in followup and graded by the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: A total of 132 patients were included, with 1 patient having synchronous breast cancer treated in each breast. Median followup was 20.0 months (range, 2.7-37.4 months). The median age at diagnosis was 61 years (range, 41-83 years). Forty-two lesions (32%) were in situ, 88 lesions (66%) were Stage 1, and 3 (2%) lesions were Stage 2. The median planning target volume was 58.2 cc (range, 24.2-109.9 cc), median V150 was 26.3 cc (range, 11.5-47.5 cc), and median V200 was 13.0 cc (range, 6.3-26.1 cc). On a pain scale of 0-10 (10 = worst pain), pain was worst on Day 2 of treatment, with an average score of 0.46. There was one acute skin infection; there were three late skin infections, two of which was Grade 3. Other late toxicities were Grade 1 or 2: hyperpigmentation (44%), telangiectasia (0.8%), seroma (9%), fat necrosis (5%), and fibrosis (12%). Crude local recurrence rate was 4%. CONCLUSION: SAVI is a safe treatment option for patients who are candidates for accelerated partial breast irradiation. Local control seems to be excellent, but longer followup is needed.

Phosphodiesterase 1A modulates cystogenesis in zebrafish.

Substantial evidence indicates the importance of elevated cAMP in polycystic kidney disease (PKD). Accumulation of cAMP in cystic tissues may be, in part, caused by enhanced adenylyl cyclase activity, but inhibition of cAMP degradation by phosphodiesterases (PDE) likely has an important role, because cAMP is inactivated much faster than it is synthesized. PDE1 is the only PDE family activated by Ca(2+), which is reduced in PKD cells. To assess the contribution of the PDE1A subfamily to renal cyst formation, we examined the expression and function of PDE1A in zebrafish. We identified two splice isoforms with alternative starts corresponding to human PDE1A1 and PDE1A4. Expression of the two isoforms varied in embryos and adult tissues, and both isoforms hydrolyzed cAMP with Ca(2+)/calmodulin dependence. Depletion of PDE1A in zebrafish embryos using splice- and translation-blocking morpholinos (MOs) caused pronephric cysts, hydrocephalus, and body curvature. Human PDE1A RNA and the PKA inhibitors, H89 and Rp-cAMPS, partially rescued phenotypes of pde1a morphants. Additionally, MO depletion of PDE1A aggravated phenotypes in pkd2 morphants, causing more severe body curvature, and human PDE1A RNA partially rescued pkd2 morphant phenotypes, pronephric cysts, hydrocephalus, and body curvature. Together, these data indicate the integral role of PDE1A and cAMP signaling in renal development and cystogenesis, imply that PDE1A activity is altered downstream of polycystin-2, and suggest that PDE1A is a viable drug target for PKD.