Orthodontic management of dentofacial skeletal deformities

The treatment of complex malocclusions with overriding skeletal discrepancies requires an exceptional amount of pretreatment planning. The roles of the orthodontist and the surgeon are equally important. Sufficient input from each member of the orthognathic surgical team is necessary before any patient care is delivered. Because the goals of presurgical orthodontic treatment are more often than not opposite to the routine orthodontic regimen, detailed planning, using diagnostic orthodontic set-ups and predictive visual imaging, is often needed to confirm the procedures necessary to create an aesthetic and functional result. Without this integrated team approach, successful outcomes of treatment can be problematic.     

Epinephrine enhances lysosomal enzyme delivery across the blood brain barrier by up-regulation of the mannose 6-phosphate receptor

Delivering therapeutic levels of lysosomal enzymes across the blood-brain barrier (BBB) has been a pivotal issue in treating CNS storage diseases, including the mucopolysaccharidoses. An inherited deficiency of beta-glucuronidase (GUS) causes mucopolysaccharidosis type VII that is characterized by increased systemic and CNS storage of glycosaminoglycans. We previously showed that the neonate uses the mannose 6-phosphate (M6P) receptor to transport phosphorylated GUS (P-GUS) across the BBB and that this transporter is lost with maturation. Induction of expression of this BBB transporter would make enzyme replacement therapy in the adult possible. Here, we tested pharmacological manipulation with epinephrine to restore functional transport of P-GUS across the adult BBB. Epinephrine (40 nmol) coinjected i.v. with (131)I-P-GUS induced the transport across the BBB in 8-week-old mice. The brain influx rate of (131)I-P-GUS (0.29 mul/g per min) returned to the level seen in neonates. Capillary depletion showed that 49% of the (131)I-P-GUS in brain was in brain parenchyma. No increases of influx rate or the vascular space for (125)I-albumin, a vascular marker, was observed with epinephrine (40 nmol), showing that enhanced passage was not caused by disruption of the BBB. Brain uptake of (131)I-P-GUS was significantly inhibited by M6P in a dose-dependent manner, whereas epinephrine failed to increase brain uptake of nonphosphorylated GUS. Thus, the effect of epinephrine on the transport of (131)I-P-GUS was ligand specific. These results indicate that epinephrine restores the M6P receptor-mediated functional transport of (131)I-P-GUS across the BBB in adults to levels seen in the neonate.     

Preparation and administration of androgen deprivation therapy products: Retrospective survey results

Leuprolide acetate (LA) is a gonadotropin-releasing hormone agonist used as androgen deprivation therapy for advanced prostate cancer. LA is available in formulations intended for intramuscular (IM-LA) or subcutaneous (SC-LA) administration. Post-marketing reports have noted handling errors associated with the preparation and administration of SC-LA. This study gathered real-world evidence on administration and management of IM-LA and SC-LA in large, urology- or oncology-based practices. Over 200 staff were invited; 151 participated in an online survey. Main outcomes were time for each step of the ordering, inventory, mixing and administration processes. Mean values and standard errors are reported for continuous variables, and frequency and percentage are reported for categorical variables. Comparisons between groups were made with t tests and chi-square tests as appropriate. For IM-LA and SC-LA, ease of ordering and time to place an order (10.8 ± 1.3 vs. 10.6 ± 1.4 min, respectively) were similar. IM-LA was associated with a shorter time to complete preparation (2.5 ± 0.2 vs. 6.1 ± 0.6 min, P < 0.001) compared with SC-LA. This difference of 3.6 min per preparation could result in substantial time savings annually ranging from 120 h per year to 240 h per year in clinical practices administering 2000 injections per year or 4000 injections per year, respectively. For IM-LA vs. SC-LA, greater ease of preparation was reported by 64% vs. 43% of respondents, respectively. Over 15% of respondents used injection sites inconsistent with prescribing information, regardless of the type of injection. This study found that it takes a significantly shorter time to prepare and administer IM-LA than SC-LA in large urology- and oncology-based practices. The time saved could be utilized for other tasks such as seeing additional patients. Use of injection sites inconsistent with prescribing information suggests a need for more training of nursing staff in the proper administration of these drugs to ensure adequate testosterone suppression and patient safety.