Background Papillary fibroelastomas are rare, benign cardiac tumors. They are predominantly asymptomatic. However, they can lead to serious complications, namely thromboembolic events. Symptomatic lesions can be managed primarily with surgical excision and valvular preservation. Controversy exists as to the management of asymptomatic lesions. Methods All patients diagnosed with cardiac papillary fibroelastoma between 1996 and 2012 at a single institution were queried for clinical and pathologic characteristics. Results Twenty-three patients with 29 lesions were identified. Most lesions were solitary, less than 1.0 cm in diameter, and occurred in patients greater than 60 years of age. The most common presentation was thromboembolic complication. All were managed successfully with surgical excision. One patient developed a recurrence or metachronous lesion within 3 months of initial surgical intervention. Conclusions Papillary fibroelastomas are rare, benign, predominantly asymptomatic cardiac tumors that can cause potentially serious complications. The natural history and etiology of papillary fibroelastomas are largely unknown. Controversy exists over the management of asymptomatic lesions. However, there is consensus that symptomatic lesions should undergo surgical excision with valvular preservation when possible. A unique case of a possible papillary fibroelastoma recurrence is also described.

Chronic granulomatous disease is an inherited immunodeficiency in which phagocytes fail to generate superoxide and its metabolites, resulting in severe recurrent infections and frequent hospitalizations. Chronic illness and frequent hospitalizations can affect growth and development as well as social and educational opportunities. Since no data have been reported on cognitive functioning in patients with this illness, the authors sought to examine cognitive function in a group of patients with chronic granulomatous disease. A retrospective chart review of 26 patients seen and followed at the National Institutes of Health who had received cognitive testing at the request of parent or staff was performed. Demographic information including medical, psychiatric, and developmental histories was gathered. Six patients (23%) were found to have an IQ of 70 or below, indicative of cognitive deficits, and all of those patients had defects in the membrane-linked cytochrome b558. The prevalence of cognitive deficits in this selected population of chronic granulomatous disease patients was high. The determination of the true distribution of cognitive functioning in the general chronic granulomatous disease population is important, since cognitive deficits have implications for educational planning and potential therapies such as transplantation and gene therapy in children.

Outcomes of patients with complex CAD undergoing the optimal treatment strategy recommended by the MHT were similar to those of published national standards. Implementation of the MHT approach for patients with complex CAD is safe and efficacious.

Background The adenosine triphosphate-sensitive potassium (KATP) channel opener, diazoxide, preserves myocyte volume homeostasis and contractility during stress via an unknown mechanism. Pharmacologic overlap has been suggested between succinate dehydrogenase (SDH) activity and KATP channel modulators. Diazoxide may be cardioprotective due to the inhibition of SDH which may form a portion of the mitochondrial KATP channel. To determine the role of inhibition of SDH in diazoxide's cardioprotection, this study utilized glutathione to prevent the inhibition of SDH. Methods SDH activity was measured in isolated mitochondria exposed to succinate (control), malonate (inhibitor of succinate dehydrogenase), diazoxide, and varying concentrations of glutathione alone or in combination with diazoxide. Enzyme activity was measured by spectrophotometric analysis. To evaluate myocyte volume and contractility, cardiac myocytes were superfused with Tyrode's physiologic solution (20 minutes), followed by test solution (20 minutes) including: Tyrode's, hyperkalemic cardioplegia (stress), cardioplegia + diazoxide, cardioplegia + diazoxide + glutathione, or glutathione alone; followed by Tyrode's (20 minutes). Myocyte volume and contractility were recorded using image grabbing software. Results Both malonate and diazoxide inhibited succinate dehydrogenase. Glutathione prevented the inhibition of succinate dehydrogenase by diazoxide in a dose dependent manner. The addition of diazoxide prevented the detrimental myocyte swelling due to cardioplegia alone and this benefit was lost with the addition of glutathione. However, glutathione elicited an independent cardioprotective effect on myocyte contractility. Conclusion The ability of diazoxide to provide beneficial myocyte homeostasis during stress involves the inhibition of succinate dehydrogenase, which may also involve the opening of a purported mitochondrial KATP channel.

Background Diazoxide maintains myocyte volume and contractility during stress via an unknown mechanism. The mechanism of action may involve an undefined (genotype unknown) mitochondrial adenosine triphosphate-sensitive potassium (mKATP) channel and is dependent upon the KATP channel subunit SUR1. KATP channel openers have been shown to inhibit succinate dehydrogenase (SDH) and a gene for a portion of SDH has been found in the SUR intron. Thus, diazoxide may be cardioprotective via inhibition of SDH, which may form part of a KATP channel or share its genetic material. This study investigated the role of inhibition of SDH by diazoxide and its relationship to the SUR1 subunit. Study Design Mitochondria were isolated from wild type and SUR1 knockout mice. Succinate dehydrogenase activity was measured by spectrophotometric analysis of 2,6-Dichloroindophenol reduction for 20 minutes as the relative change in absorbance over time. Mitochondria were treated with succinate (20 mM), succinate + 1% dimethylsulfoxide, succinate + malonate (8 mM) (competitive inhibitor of SDH), or succinate + diazoxide (100 μM). Results Both malonate and diazoxide inhibit SDH activity in mitochondria of wild type mice and in mice lacking the SUR1 subunit (p<0.05 vs control). Conclusions The ability of DZX to inhibit SDH persists even after the deletion of the SUR1 gene. Therefore, the enzyme complex SDH is not dependent on the SUR1 gene. The inhibition of SDH by DZX may play a role in the cardioprotection afforded by DZX, however, this role is independent of the KATP channel subunit SUR1.