Infant coarctation: a spectrum in clinical presentation and treatment

Between 1975 and 1985, 125 infants 2 to 365 days old (majority, 30 days old or less) with coarctation of the aorta underwent surgical repair. Forty-seven patients (38%) had severe congestive heart failure (CHF), metabolic acidosis, and poor systemic perfusion. The predominant operative technique was synthetic patch aortoplasty (100 patients); the remaining 25 had an end-to-end anastomosis. There were no operative deaths. Perioperative complications were minimized with the synthetic patch technique (less than 15%). For patients surviving at least 3 months after repair, the arm-leg systolic blood pressure gradient was relieved in 82% (71/87) of the patients having patch aortoplasty versus 65% (15/23) of the patients with end-to-end anastomosis. Although the rate of reoperation between the two groups was similar (patch, 5 [6%]; end-to-end, 3 [13%], two of the reoperations in the patch group were for preexisting hypoplastic transverse aortic arch. Late deaths (20 patients, 16%) were due to other major associated cardiac anomalies. Patch aneurysms have not occurred. Expedient use of synthetic patch aortoplasty has decreased perioperative complications, relieved coarctation gradients for CHF, increased early survival even in the presence of complex or associated cardiac anomalies, and has an acceptable rate of recurrent coarctation (6 to 13%).     

Health care access and glycemic control in youth and young adults with type 1 and type 2 diabetes in South Carolina

Affordability and geographic accessibility are key health care access characteristics. We used data from 481 youth and young adults (YYA) with diabetes (389 type 1, 92 type 2) to understand the association between health care access and glycemic control as measured by HbA_1c values. In multivariate models, YYA with state or federal health insurance had HbA_1c percentage values 0.68 higher (P = 0.0025) than the privately insured, and those without insurance 1.34 higher (P < 0.0001). Not having a routine diabetes care provider was associated with a 0.51 higher HbA_1c (P = 0.048) compared to having specialist care, but HbA_1c did not differ significantly (P = 0.069) between primary vs specialty care. Distance to utilized provider was not associated with HbA_1c among YYA with a provider (P = 0.11). These findings underscore the central role of health insurance and indicate a need to better understand the root causes of poorer glycemic control in YYA with state/federal insurance.     

Synthesis of a dual carbon-14-labeled calcitonin gene-related peptide receptor antagonist for use in a human absorption–distribution–metabolism–elimination study

Oral calcitonin gene-related peptide (CGRP) receptor antagonists have been shown to be effective in the acute and preventive treatment of migraine. CGRP receptor antagonists offer safety advantages over triptans because they are not active vasoconstrictors, which reduces cardiovascular risks. Bristol Myers Squibb discovered a high affinity CGRP receptor antagonist BMS-927711 for the treatment of migraine now FDA approved as Nurtec® ODT (rimegepant). Dual-labeled [¹⁴C]-BMS-927711 was prepared and used in a human absorption–distribution–metabolism–elimination (ADME) study. A dual-labeled analog of BMS-927711 was required to fully track the compound's metabolic transformation. The carbon-14-labeled synthesis of both right side and left side portions of [¹⁴C]-BMS-927711 is described.     

Expression of key hypoxia sensing prolyl‐hydroxylases PHD1, ‐2 and ‐3 in pancreaticobiliary cancer

Gossage L, Zaitoun A, Fareed K R, Turley H, Aloysius M, Lobo D N, Harris A L & Madhusudan S
(2010) Histopathology 56, 908–920
Expression of key hypoxia sensing prolyl‐hydroxylases PHD1, ‐2 and ‐3 in pancreaticobiliary cancer Aims: Tumour hypoxia is associated with an aggressive phenotype and resistance to chemotherapy and radiotherapy. The aim was to investigate whether key hypoxia sensing prolyl hydroxylases PHD1, PHD2 and PHD3 are dysregulated in pancreaticobiliary cancers, and to evaluate their potential clinical significance. Methods and results: Formalin‐fixed human pancreatic tissue from 120 consecutive patients undergoing pancreatic resections between June 2001 and June 2006 was constructed into tissue microarrays. Expression of PHD1, PHD2 and PHD3 was analysed using immunohistochemistry and correlated with clinicopathological variables and disease‐specific overall survival. PHD1, PHD2 and PHD3 were significantly overexpressed in pancreaticobiliary tumours compared with normal pancreatic ductal tissues (P = 0.03, P < 0.0001 and P < 0.0001, respectively). PHD3 expression in tumour tissue was associated with a trend towards worse overall disease‐specific survival in ampullary adenocarcinomas (P = 0.035) and pancreatic adenocarcinomas (P = 0.084). Absence of PHD1 expression was significantly associated with perineural invasion in pancreatic adenocarcinomas (P = 0.02) and a trend towards significance was also seen for absence of PHD2 expression in pancreatic adenocarcinomas (P = 0.04). Conclusions: Our results provide the first clinical evidence that PHD1, PHD2 and PHD3 may be involved in pancreaticobiliary tumorigenesis.