Holdengolden0687
To describe the elements critical to successful middle temporal artery periosteal rotational flap harvest and utilization based on the anatomic features of the middle temporal artery.
Description of anatomy based on cadaver dissection.
Seventy temporal fossa dissections were performed on 35 adult human cadavers.
Sixty-nine of 70 dissections had an identifiable middle temporal artery muscular branch pedicle in the periosteum deep to the temporalis muscle. Pedicle length was at least 7 cm in 32 of 38 (84%) male cadavers and in 20 of 31 (65%) female cadavers (P = 0.054), whereas the average length required to reach the digastric ridge from the pedicle base to the digastric ridge in a mastoidectomy cavity was 5.2 cm. The pedicle sharply transitions from a posterior to a posterior-superior course 0.93 cm superior (range 0.5-1.9 cm) and 0.04 cm posterior (range 1.4 cm posterior-0.7 cm anterior) to the spine of Henle. Branching occurred in 26 of 69 pedicles (38%), and 20 of 31 (65%) branches were oriented posteriorly. If temporalis muscle fibers are not incorporated into the flap, the thickness is roughly three times that of a standard temporalis fascia graft.
The muscular branch of the middle temporal artery is reliably identified in the periosteum deep to the posterior aspect of the temporalis muscle, and this vessel is sufficiently robust to provide axial blood supply to a rotational periosteal flap that has sufficient thickness and length to allow a variety of applications in otologic surgery.
NA. Laryngoscope, 1261426-1432, 2016.
NA. Laryngoscope, 1261426-1432, 2016.The volume of scientific literature continues to expand and decision-makers are faced with increasingly unmanageable volumes of evidence to assess. Systematic reviews (SRs) are powerful tools that aim to provide comprehensive, transparent, reproducible and updateable summaries of evidence. SR methods were developed, and have been employed, in healthcare for more than two decades, and they are now widely used across a broad range of topics, including environmental management and social interventions in crime and justice, education, international development, and social welfare. Despite these successes and the increasing acceptance of SR methods as a 'gold standard' in evidence-informed policy and practice, misconceptions still remain regarding their applicability. The aim of this article is to separate fact from fiction, addressing twelve common misconceptions that can influence the decision as to whether a SR is the most appropriate method for evidence synthesis for a given topic. Through examples, we illustrate the flexibility of SR methods and demonstrate their suitability for addressing issues on environmental health and chemical risk assessment.Magnetic resonance imaging (MRI) is an excellent imaging modality. However the low sensitivity of the technique poses a challenge to achieving an accurate image of function at the molecular level. To overcome this, contrast agents are used; typically gadolinium based agents for T1 weighted imaging, or iron oxide based agents for T2 imaging. Traditionally, only one imaging mode is used per diagnosis although several physiological situations are known to interfere with the signal induced by the contrast agents in each individual imaging mode acquisition. Recently, the combination of both T1 and T2 imaging capabilities into a single platform has emerged as a tool to reduce uncertainties in MR image analysis. CIL56 nmr To date, contradicting reports on the effect on the contrast of the coupling of a T1 and T2 agent have hampered the application of these specialised probes. Herein, we present a systematic experimental study on a range of gadolinium-labelled magnetite nanoparticles envisioned to bring some light into the mechanism of interaction between T1 and T2 components, and advance towards the design of efficient (dual) T1 and T2 MRI probes. Unexpected behaviours observed in some of the constructs will be discussed. In this study, we demonstrate that the relaxivity of such multimodal probes can be rationally tuned to obtain unmatched potentials in MR imaging, exemplified by preparation of the magnetite-based nanoparticle with the highest T2 relaxivity described to date.Human cytochrome P450 3A4 (CYP3A4) is a key xenobiotic-metabolizing enzyme that oxidizes and clears the majority of drugs. CYP3A4 inhibition may lead to drug-drug interactions, toxicity, and other adverse effects but, in some cases, could be beneficial and enhance therapeutic efficiency of coadministered pharmaceuticals that are metabolized by CYP3A4. On the basis of our investigations of analogs of ritonavir, a potent CYP3A4 inactivator and pharmacoenhancer, we have built a pharmacophore model for a CYP3A4-specific inhibitor. This study is the first attempt to test this model using a set of rationally designed compounds. The functional and structural data presented here agree well with the proposed pharmacophore. In particular, we confirmed the importance of a flexible backbone, the H-bond donor/acceptor moiety, and aromaticity of the side group analogous to Phe-2 of ritonavir and demonstrated the leading role of hydrophobic interactions at the sites adjacent to the heme and phenylalanine cluster in the ligand binding process. The X-ray structures of CYP3A4 bound to the rationally designed inhibitors provide deeper insights into the mechanism of the CYP3A4-ligand interaction. Most importantly, two of our compounds (15a and 15b) that are less complex than ritonavir have comparable submicromolar affinity and inhibitory potency for CYP3A4 and, thus, could serve as templates for synthesis of second generation inhibitors for further evaluation and optimization of the pharmacophore model.The aim of this study was to characterize the profile of the proteins involved in the Hedgehog signaling pathway to aid in the understanding of the pathogenesis of oral epithelial dysplasia (OED). The proteins SHH, PTCH1, HHIP, SUFU, GLI1, and cyclin D1 were evaluated by immunohistochemistry in 25 cases of OED, 4 of non-neoplasic oral mucosa, 8 of inflammatory fibrous hyperplasia and 5 of hyperkeratosis. SHH proteins were predominant in OED cases. Although PTCH1 protein was observed in all cases, this molecule was more highly expressed in OED. The inhibitor protein SUFU was present in OED and HHIP protein was overexpressed in OED. GLI1 proteins were predominantly found in the nuclei of epithelial cells in OED. Basal and suprabasal cells in the epithelial lining were positive for cyclin D1 only in OED. In conclusion, comparative analysis of the proteins involved in the Hedgehog pathway suggests that enhanced expression of these proteins can play an important role in the biological behavior of OED.Human papillomaviruses (HPV) are oncogenic DNA viruses implicated in squamous cell carcinomas of several anatomic sites, as well as endocervical adenocarcinomas. Identification of HPV is an actionable finding in some carcinomas, potentially influencing tumor classification, prognosis, and management. We incorporated capture probes for oncogenic HPV strains 16 and 18 into a broader next-generation sequencing (NGS) panel designed to identify actionable mutations in solid malignancies. A total of 21 head and neck, genitourinary, and gynecologic squamous cell carcinomas and endocervical adenocarcinomas were sequenced as part of the UNCSeq project. Using p16 immunohistochemical results as the gold standard, we set a cutoff for proportion of aligned HPV reads that maximized performance of our NGS assay (92% sensitive, 100% specific for HPV). These results suggest that sequencing of oncogenic pathogens can be incorporated into targeted NGS panels, extending the clinical utility of genomic assays.Undifferentiated brain tumors represent a diagnostic challenge, particularly in small biopsies, with regards to their primary versus metastatic origin. The latter may show overlapping morphologic features with primary high-grade brain tumors. In recent years several new antibodies have entered the realm of daily pathology practice. PAX8 (mammalian paired box genes 1 to 9 protein encoding gene) is among these new markers and is recognized as a differentiating marker of the primary site in epithelial tumors outside of the central nervous system. A review of the literature shows lack of site-specific studies with regards to the expression of PAX8 in the central nervous system and its neoplasms. Using this marker we investigated its immunohistochemical expression in normal brain tissue and glial tumors. The immunostain was performed on tissue microarrays of 71 cores from 24 cases. We also performed PAX8 immunostain on sections from cerebellum, pons, periventricular ependymal layer, choroid plexus, pituitary, and meninges of 3 autopsy cases. Our results indicate lack of PAX8 expression by benign brain tissue. Only 1 glioblastoma core (1/9 cores) showed focal nuclear reactivity with the antibody. Our results indicate that presence of PAX8 immunoreactivity in an undifferentiated brain tumor lacking gliofibrillary acidic protein expression should prompt consideration of a metastatic tumor.Dedifferentiated endometrioid adenocarcinoma (DEAC) of the uterus or ovary is characterized by the coexistence of low-grade endometrioid adenocarcinoma and an undifferentiated carcinoma (UC) with solid sheets of medium-sized monotonous epithelial cells. This admixed carcinoma has not been widely recognized, because the solid areas of UC have usually been misdiagnosed as a solid form of FIGO grade 3 endometrioid adenocarcinoma. These tumors have been shown to be clinically aggressive; therefore, accurate diagnosis is necessary for proper patient management. We reviewed our experience with DEACs and compared them with grade 3 endometrioid carcinomas regarding their clinicopathologic, morphologic, and immunohistochemical features. Our results indicate that DEACs are clinically aggressive tumors presented at advanced stages with vascular invasions in 73% and lymph node metastases in 46%. Thirty-eight percent of cases also showed distal metastases. Clinical follow-up data revealed that all patients had either recurrent or metastatic diseases within 3 years of diagnosis, except 1 patient who remained disease free for 3 years after diagnosis. Morphologically, UC components of DEACs were composed of diffuse sheets/solid nests of medium-sized epithelial cells with scant to moderate cytoplasm, uniform vesicular nuclei, and inconspicuous nucleoli. Although UC components of DEACs are variably positive for cytokeratin, EMA, and ER, they are mostly negative for PAX8, except 1 case. Instead, well-differentiated components of DEACs and solid grade 3 endometrioid carcinoma retained all these markers. Our results indicate that DEACs exhibit significantly different clinicopathologic features from grade 3 endometrioid adenocarcinoma, and a combination of immunohistochemical stains can be helpful to differentiate them from each other.
Acquired somatic mutation Janus kinase 2 (JAK2) V617F is associated with various myeloproliferative neoplasms (MPN). Allele-specific real-time polymerase chain reaction has been widely adopted to detect mutation; however, the utility of low positive results is not well understood. The aim of this study is to investigate the clinical significance of low positivity of JAK2 V617F.
Retrospective analysis was performed for JAK2 V617F mutation tests performed using JAK2 MutaQuant kit (Ipsogen) in molecular laboratories at 2 major academic medical centers between 2010 and 2012. Cases with low positive JAK2 V617F, defined as 0.2% to 5% mutant allele, were documented. Chart review was performed for the clinical correlation.
A total of 1697 JAK2 V617F tests was performed. Forty-five cases (2.65%) yielded a low JAK2 V617F positivity (average 1.45%), the majority of which (n=26, 62%) had <1%. Eight cases had a history of MPN. The remaining cases were related to reactive conditions without a clonal disease. Our data indicate that a low positivity of JAK2 V617F can be seen in MPN as well as reactive conditions.
