Hairy leucoplakia—a clinical, histopathological and ultrastructural study in 33 patients

Thirty-three cases of hairy leucoplakia (HL) in HIV-positive patients were studied. The most frequent clinical presentation was the development of corrugated plaques on the lateral sides of the tongue without spiculations on the surface. In all biopsies, herpetic-type viral inclusions were found. In 12 out of 14 cases in whom an electromicroscopic study was carried out, only viral particles of the herpes group were found. Human papillomavirus (HPV) was not demonstrated, although by means of immunohistochemistry, positive labelling for HPV was found in 95% of the cases. The aetiopathological significance of these findings remains to be evaluated.     

A phase I study of bolus versus continuous infusion of the anti-CD19 immunotoxin, IgG-HD37-dgA, in patients with B-cell lymphoma

IgG-HD37-SMPT-dgA is a deglycosylated ricin A chain (dgA)-containing immunotoxin (IT) prepared by conjugating the monoclonal murine (MoAb) anti-CD19 antibody, HD37, to dgA using the heterobifunctional hindered disulfide linker, N-succinimidyl-oxycarbonyl-alpha-methyl-alpha-(2- pyridyldithio) toluene (SMPT). In this report, we have used two regimens for the administration of IgG-HD37-SMPT-dgA to patients with non-Hodgkin's lymphoma (NHL) in two concomitant phase I trials. One trial examined four intermittent bolus infusions administered at 48- hour intervals. The other studied a continuous infusion (CI) administered over the same 8-day period. In the intermittent bolus regimen, the maximum tolerated dose (MTD) was 16 mg/m2/8 d and the dose- limiting toxicity (DLT) consisted of vascular leak syndrome (VLS), aphasia, and evidence of rhabdomyolysis encountered at 24 mg/m2/8 d. Using the CI regimen, the MTD was defined by VLS at 19.2 mg/m2/8 d. At the MTD of both regimens, a novel toxicity, consisting of acrocyanosis with reversible superficial distal digital skin necrosis in the absence of overt evidence of systemic vasculitis, occurred in 3 patients. Of 23 evaluable patients on the bolus schedule, there was 1 persisting complete response (CR; > 40 months) and 1 partial response (PR). Of 9 evaluable patients on the continuous infusion regimen, there was 1 PR. Pharmacokinetic parameters for the bolus regimen at the MTD showed a mean maximum serum concentration (Cmax) of 1,209 +/- 430 ng/mL, with a median T1/2 beta for all courses of 18.2 hours (range, 10.0 to 80.0 hours), a volume of distribution (Vd) of 10.9 L (range, 3.1 to 34.5 L), and a clearance (CL) of 0.45 L/h (range, 0.13 to 2.3 L/h). For the CI regimen at MTD, the mean Cmax was 963 +/- 473 ng/mL, with a median T1/2 beta for all courses of 22.8 hours (range, 24.1 to 30.6 hours), a Vd of 9.4 L (range, 4.4 to 19.5 L), and a CL of 0.32 L/h (range, 0.12 to 0.55 L/h). Twenty-five percent of the patients on the bolus infusion regimen and 30% on the CI regimen made antibody against mouse Ig (HAMA) and/or ricin A chain antibody (HARA). We conclude that this IT can be administered safely and that both regimens achieve comparable peak serum concentrations at the MTD; these concentrations are similar to those achieved previously using other regimens with IgG-dgA ITs at their respective MTDs. Thus, toxicity is related to the serum level of the IT and does not differ with different targeting MoAbs.     

Application of neuroanatomical features to tractography clustering

Diffusion tensor imaging allows unprecedented insight into brain neural connectivity in vivo by allowing reconstruction of neuronal tracts via captured patterns of water diffusion in white matter microstructures. However, tractography algorithms often output hundreds of thousands of fibers, rendering subsequent data analysis intractable. As a remedy, fiber clustering techniques are able to group fibers into dozens of bundles and thus facilitate analyses. Most existing fiber clustering methods rely on geometrical information of fibers, by viewing them as curves in 3D Euclidean space. The important neuroanatomical aspect of fibers, however, is ignored. In this article, the neuroanatomical information of each fiber is encapsulated in the associativity vector, which functions as the unique “fingerprint” of the fiber. Specifically, each entry in the associativity vector describes the relationship between the fiber and a certain anatomical ROI in a fuzzy manner. The value of the entry approaches 1 if the fiber is spatially related to the ROI at high confidence; on the contrary, the value drops closer to 0. The confidence of the ROI is calculated by diffusing the ROI according to the underlying fibers from tractography. In particular, we have adopted the fast marching method for simulation of ROI diffusion. Using the associativity vectors of fibers, we further model fibers as observations sampled from multivariate Gaussian mixtures in the feature space. To group all fibers into relevant major bundles, an expectation‐maximization clustering approach is employed. Experimental results indicate that our method results in anatomically meaningful bundles that are highly consistent across subjects. Hum Brain Mapp 34:2089–2102, 2013. © 2012 Wiley Periodicals, Inc.     

The teaching of temporomandibular disorders and orofacial pain at undergraduate level in Brazilian dental schools

Objectives

Evaluate the way the topics for the study of pain mechanisms in general, and Orofacial Pain (OFP) and temporomandibular disorders (TMDs) more specifically, are addressed in undergraduate courses curricula, and also to verify the existence of specialist OFP/TMD teachers in Brazilian dental schools.

Methods

Between July 2010 and January 2011, course Coordinators/Directors of all dental schools duly registered at the Ministry of Education were invited to answer a questionnaire on topics related to OFP/TMD teaching in their institutions.

Results

Fifty-three dental schools representatives answered the questionnaire. The study of pain mechanisms was found to cover an average of less than 10% of the courses'' total time. Pharmacology, Endodontics and Physiology were identified as the departments usually responsible for addressing pain mechanisms in dental courses. Psychosocial aspects were found to occupy a very small proportion in the syllabi, while most of the content referred to biological or somatic aspects. OFP/TMD is addressed by a specific department in only 28.4% of the participating dental schools, while in most cases (46.3%), OFP/TMD is under the responsibility of the Prosthodontics department. Only 38.5% of respondents indicated that they had a specialist OFP/TMD teacher in their Schools.

Conclusion

Among the Brazilian dental schools participating in the study, the teaching of OFP/TMD was found to be insufficient, segmented or with an extremely restricted focus. This initial assessment indicates that Curricular Guidelines for the study of OFP/TMD at undergraduate dental schools should be developed and implemented to facilitate their appropriate inclusion into the curricula and in specific pedagogical projects.