Development of Pulmonary Hypertension During Treatment with Diazoxide: A Case Series and Literature Review.

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infancy. The mainstay of medical management for CHI is diazoxide. Diazoxide inhibits insulin release from the pancreas, but also causes smooth muscle relaxation and fluid retention so it is typically given with chlorothiazide. In July 2015, the FDA issued a drug safety communication warning that pulmonary hypertension (PH) had been reported in 11 infants being treated with diazoxide and that the PH resolved with withdrawal of diazoxide. All three of the cases in our hospital were admitted to the neonatal intensive care unit (NICU) for hypoglycemia. All patients received thorough radiologic and laboratory evaluations related to their diagnosis of CHI. All initially improved when diazoxide was initiated. Case 1 and case 3 were discharged from the NICU on diazoxide and chlorothiazide. Case 2 developed pulmonary hypertension while still in the NICU days after an increase in diazoxide dosing. Case 1 presented to the emergency room in respiratory distress shortly after discharge from the NICU with evidence of PH and heart failure. Case 3 presented to the emergency room after 2 weeks at home due to a home blood glucose reading that was low and developed PH and heart failure while an inpatient. Discontinuation of diazoxide led to resolution of all three patients' PH within approximately one week. The experience of our hospital indicates that pulmonary hypertension may be more common than previously thought in infants taking diazoxide. It is unclear if these symptoms develop slowly over time or if there is some other, as yet undescribed, trigger for the pulmonary hypertension. Our hospital's experience adds to the body of evidence and suggests these infants may benefit from more surveillance with echocardiography.

Ebola Virus Disease Simulation Case Series: Patient With Ebola Virus Disease in the Prodromal Phase of Illness (Scenario 1), the "Wet" Gastrointestinal Phase of Illness (Scenario 2), and the Late, Critically Ill Phase of Disease (Scenario 3).

INTRODUCTION: As part of an international response to the Ebola virus disease (EVD) outbreak, the US Department of Defense has deployed thousands of personnel to help train and augment international health care workers. The transmission risk of this deadly virus to health care workers has been extreme, demonstrating the importance of safe practices while caring for these patients. Medical simulation training is well recognized as an integral component for disease outbreak preparedness. Therefore, the US Government created a program of instruction that outlines a formalized EVD training program, using high-fidelity simulation, which projects both an understanding of the disease and its transmission risks. METHODS: Two 5-day training courses were established to provide training to the 65-member Department of Defense Ebola Response Team, which would be activated during a stateside Ebola outbreak. This training consisted of Ebola-specific protocols, personal protective equipment familiarization, and scenario-based certification for physicians, nurses, and public health trainers. Simulation was used to replicate the work environment inside an Ebola treatment unit. RESULTS: Three comprehensive clinical scenarios covering a wide spectrum of EVD presentations were designed around details of published cases to provide the most realistic and relevant EVD training available. The authors conducted 10 iterations of the 3 EVD clinical scenarios totaling more than 1100 hours of simulation training. CONCLUSIONS: Quality practical exercises to include specialized task performance and collective teamwork training relied heavily on dedicated facilities and realistic medical simulation resulting in valuable lessons learned. In future iterations, these characteristics would be imperative to a successful training course.

Germline p53 mutation in a Micronesian child with adrenocortical carcinoma and subsequent osteosarcoma.

In 1990, an 18-month-old Micronesian girl was initially diagnosed with a right adrenocortical carcinoma. More than a decade later (2003), she was diagnosed with metastatic osteosarcoma with the primary in her right proximal fibula. Given this child's remarkable history of malignancy, she underwent testing for a genetic mutation that is associated with increased cancer formation. One such cancer syndrome is called Li-Fraumeni syndrome where approximately 70% of patients carry a genetic mutation in the p53 tumor suppressor gene. Patients with LFS are at risk for developing cancers of the breast, soft tissues, brain, bone, adrenal gland, and blood cells. Mutational analysis of our patient did reveal the presence of a germline mutation of the p53 tumor suppressor gene. She was found to have a base pair change (A-->C) at nucleotide 394 resulting in a lysine to glutamine amino acid change at codon 132 (K132Q), which remarkably has never been described in association with either adrenocortical carcinoma or osteosarcoma.

Heteroleptic copper dipyrromethene complexes: synthesis, structure, and coordination polymers.

The synthesis of neutral [Cu(dpm)2] and [Cu(dpm)(acac)] (dpm = dipyrromethene, acac = acetylacetonato) complexes is presented. The formation of the asymmetric metal complexes was monitored by electronic absorption and infrared spectroscopy. Two of the complexes investigated, containing pyrdpm ligands (pyrdpm = pyridyldipyrromethene), form 1-dimensional coordination polymers. The coordination polymers formed by these complexes have been characterized by single-crystal X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. The complexes possess square pyramidal coordination geometries with the apical position occupied by the meso-pyridyl donor of a neighboring complex in the crystal lattice. The features of these coordination complexes that facilitate formation of extended solids have been probed. Symmetric [Cu(pyrdpm)2] complexes are unable to form coordination solids due to steric hindrance at the metal center. Use of cyano donors in complexes such as [Cu(cydpm)(acac)] (cydpm = cyanodipyrromethene) in lieu of pyridyl donors also fail to form network solids. Through these systematic studies, both the basic coordination chemistry of these complexes and the fundamental design requirements for synthesizing this novel class of coordination polymers have been defined.