Introduction: There is growing interest in, and emphasis on, electronic teaching tools in medicine. Despite relevant testing on the United States Medical Licensing Examination (USMLE), American medical schools offer limited training in skin disorders. Teaching visual topics like dermatology in classroom formats is challenging. We hypothesized that an electronic module would enhance students' dermatology competency. Methods: A self-directed, case-based module was created. To test its efficacy, 40 medical students were randomized to have module access (interventional group) or none (conventional group). Learning outcomes were compared using a multiple-choice exam, including questions relevant and irrelevant to the module. Outcomes included proportions of correctly answered module questions (module scores) and nonmodule questions (nonmodule scores). Difference scores were calculated: (module score) − (nonmodule score). Positive values indicated that knowledge of module questions surpassed that of
Metastatic melanoma remains difficult to treat despite recent approvals of several new drugs. Recently we reported encouraging results of Phase I clinical trial of radiolabeled with 188Re murine monoclonal IgM 6D2 to melanin in patients with Stage III/IV melanoma. Subsequently we generated a novel murine IgG 8C3 to melanin. IgGs are more amenable to humanization and cGMP (current Good Manufacturing Practice) manufacturing than IgMs. We performed comparative structural analysis of melanin-binding IgM 6D2 and IgG 8C3. The therapeutic efficacy of 213Bi- and 188Re-labeled 8C3 and its comparison with anti-CTLA4 immunotherapy was performed in B16-F10 murine melanoma model. The primary structures of these antibodies revealed significant homology, with the CDRs containing a high percentage of positively charged amino acids. The 8C3 model has a negatively charged binding surface and significant number of aromatic residues in its H3 domain, suggesting that hydrophobic interactions contribute to the antibody-melanin interaction. Radiolabeled IgG 8C3 showed significant therapeutic efficacy in murine melanoma, safety towards healthy melanin-containing tissues and favorable comparison with the anti-CTLA4 antibody. We have demonstrated that antibody binding to melanin relies on both charge and hydrophobic interactions while the in vivo data supports further development of 8C3 IgG as radioimmunotherapy reagent for metastatic melanoma.
Abbreviations: CT, computed tomography; HVOO, hepatic venous outflow obstruction; IVC, inferior vena cava; LHV, left hepatic vein; NPV, negative predictive value; OLT, orthotopic liver transplantation; PPV, positive predictive value; TJLB, transjugular liver biopsy; US, ultrasound.Abstract Objective: To investigate Doppler US and catheter venogram correlates to improve detection of transplant HVOO and avoid unnecessary invasive imaging procedures. Materials and methods: A retrospective review was performed in all pediatric OLT patients undergoing catheter venography of the hepatic veins between 2007 and 2017 at a single large tertiary pediatric liver transplant institution. Results: Forty-four transplant hepatic venograms in 32 OLT patients were included (mean 1.38, range 1-4 venograms per patient). All venograms were preceded by an independent Doppler US examination. Twenty-one (47.7%) venograms were performed for the investigation of suspected HVOO based on Doppler US alone, 19(43.2%) were performed for TJLB without suspected HVOO, 4 (9.1%) were performed for both. Sixteen (36.3%) instances of >50% anastomotic stenosis were identified.Mean peak anastomotic velocities were 208 cm/s and 116 cm/s in the presence and absence of a >50% venographic stenosis, respectively (P < 0.004). In all cases where there was a monophasic waveform seen on Doppler US, there was a > 50% stenosis seen on hepatic vein venogram. In all cases where a triphasic waveform was seen on Doppler US, there was no stenosis seen on hepatic vein venogram. Conclusion: While a Doppler US velocity threshold providing both high sensitivityand specificity has yet to be identified, increasing peak anastomotic velocity and decreasing intrahepatic venous velocity correlate strongly with venographic outflow stenosis. The presence of a triphasic intrahepatic waveform provides good NPV. K E Y W O R D S Doppler ultrasound, hepatic vein, liver, pediatric, transplant, venography TA B L E 1 Patient demographics and transplant details Patient characteristics Age, mean (range) 9.3 y (6 mo-20 y)Weight, mean (range) 37 kg (7-102 kg)
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