Direct immunofluorescence is of limited utility in patients with low clinical suspicion for an oral autoimmune bullous disorder

ObjectivesOral autoimmune bullous disorders show clinical overlap with diseases such as lichen planus and others that may cause desquamative gingivitis. As direct immunofluorescence is expensive, we sought to determine if routine histology alone would be sufficient to distinguish between oral autoimmune bullous disorders and mimics.MethodsWe searched the records for patients with a suspected oral autoimmune bullous disorder who underwent biopsies for concurrent routine histologic evaluation and direct immunofluorescence and who had at least one followâ up visit. Cases were separated into high and low suspicion subgroups based on clinical findings.ResultsWithin 148 cases, the sensitivity of routine histology alone was 0.810, with a negative predictive value of 0.889. However, the specificity was 0.989 with a positive predictive value of 0.979. Of the high suspicion cases, 57 (47.1%) were found to be consistent with an oral autoimmune bullous disorder, with a total of 11 histologic false negatives. 8 cases, all in the high suspicion subgroup, showed indeterminate direct immunofluorescence results. There were no histologic false negatives or inconclusive direct immunofluorescence results in the low suspicion subgroup.ConclusionsIn patients with a low clinical suspicion for an oral autoimmune bullous disorder, it is reasonable and more costâ effective to evaluate the lesion with routine histology alone.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153107/1/odi13159_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153107/2/odi13159.pd

Extensive Dental Caries in Patients with Oral Chronic Graft-versus-Host Disease

The oral cavity is one of the sites most frequently affected by chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (alloHCT) and can be a significant source of patient morbidity due to both mucosal and salivary gland involvement. The development of dental decay is a potentially devastating oral complication that has only rarely been reported in the transplantation literature. The purpose of this study was to comprehensively characterize a cohort of patients with cGVHD who subsequently developed extensive dental caries. A retrospective case-record review was conducted for patients who had undergone alloHCT at Dana-Farber/Brigham and Women's Cancer Center between 1990 and 2010 and developed cGVHD-associated rampant dental decay. All patients underwent dental evaluation, involving soft and hard tissue examination and dental radiography, before and after alloHCT. Any dental caries diagnosed at the pre-alloHCT evaluation were treated definitively, such that all patients were considered free of caries at the time of admission for alloHCT. A total of 21 patients were identified, with a median time of cGVHD onset of 5.4 months (range, 2.2-18.5 months) after alloHCT. All patients were diagnosed with oral cGVHD, with 90% demonstrating mucosal involvement and 95% demonstrating salivary gland involvement. Post-alloHCT dental evaluation was performed at a median of 22 months (range, 4-81) after alloHCT, when 10 patients were diagnosed with gross caries and 8 patients had 4 or more affected teeth. Cervical and interproximal patterns of dental caries were frequently diagnosed. The proportions of patients with gross caries, one surface caries, and more than one surface caries (classified as 0, 1-3, and ≥4, respectively) were significantly higher after alloHCT than before alloHCT, with at least 50% of patients experiencing an increase. Patients with oral cGVHD who were free of caries at the time of transplantation developed extensive areas of cervical decay at a median of less than 2 years after alloHCT. This is the first comprehensive characterization of this severe late complication of alloHCT and oral cGVHD. Greater awareness by transplantation oncologists and dentists, as well as more aggressive preventive measures, are needed, as are further prospective studies to better elucidate the incidence of this complication, identify risk factors, and evaluate the effectiveness of preventive interventions

Therapeutic genome editing for Charcot-marie-tooth disease type 1a

Charcot-Marie-Tooth 1A (CMT1A) is the most common inherited neuropathy without a known therapy, which is caused by a 1.4 Mb duplication on human chromosome 17, which includes the gene encoding the peripheral myelin protein of 22 kDa (PMP22). Overexpressed PMP22 protein from its gene duplication is thought to cause demyelination and subsequently axonal degeneration in the peripheral nervous system (PNS). Here, we targeted regulatory region of human PMP22 to normalize overexpressed PMP22 level in C22 mice, a mouse model of CMT1A harboring multi copies of human PMP22. Direct local intraneural delivery of CRISPR/Cas9 designed to target TATA-box of PMP22 before the onset of disease, downregulates gene expression of PMP22 and preserves both myelin and axons. Notably, the same approach was effective in partial rescue of demyelination even after the onset of disease. Collectively, our data present a potential therapeutic efficacy of CRISPR/Cas9-mediated targeting of regulatory region of PMP22 to treat CMT1A. Please click Additional Files below to see the full abstract

Population Genetic Structure of Peninsular Malaysia Malay Sub-Ethnic Groups

Patterns of modern human population structure are helpful in understanding the history of human migration and admixture. We conducted a study on genetic structure of the Malay population in Malaysia, using 54,794 genome-wide single nucleotide polymorphism genotype data generated in four Malay sub-ethnic groups in peninsular Malaysia (Melayu Kelantan, Melayu Minang, Melayu Jawa and Melayu Bugis). To the best of our knowledge this is the first study conducted on these four Malay sub-ethnic groups and the analysis of genotype data of these four groups were compiled together with 11 other populations' genotype data from Indonesia, China, India, Africa and indigenous populations in Peninsular Malaysia obtained from the Pan-Asian SNP database. The phylogeny of populations showed that all of the four Malay sub-ethnic groups are separated into at least three different clusters. The Melayu Jawa, Melayu Bugis and Melayu Minang have a very close genetic relationship with Indonesian populations indicating a common ancestral history, while the Melayu Kelantan formed a distinct group on the tree indicating that they are genetically different from the other Malay sub-ethnic groups. We have detected genetic structuring among the Malay populations and this could possibly be accounted for by their different historical origins. Our results provide information of the genetic differentiation between these populations and a valuable insight into the origins of the Malay sub-ethnic groups in Peninsular Malaysia

Identification of Close Relatives in the HUGO Pan-Asian SNP Database

The HUGO Pan-Asian SNP Consortium has recently released a genome-wide dataset, which consists of 1,719 DNA samples collected from 71 Asian populations. For studies of human population genetics such as genetic structure and migration history, this provided the most comprehensive large-scale survey of genetic variation to date in East and Southeast Asia. However, although considered in the analysis, close relatives were not clearly reported in the original paper. Here we performed a systematic analysis of genetic relationships among individuals from the Pan-Asian SNP (PASNP) database and identified 3 pairs of monozygotic twins or duplicate samples, 100 pairs of first-degree and 161 second-degree of relationships. Three standardized subsets with different levels of unrelated individuals were suggested here for future applications of the samples in most types of population-genetics studies (denoted by PASNP1716, PASNP1640 and PASNP1583 respectively) based on the relationships inferred in this study. In addition, we provided gender information for PASNP samples, which were not included in the original dataset, based on analysis of X chromosome data

Oral lichen planus: REU scoring system correlates with pain

Objectives. The objectives of this study were to correlate a semiquantitative scoring system for oral lichen planus (OLP) with pain before versus after treatment and to analyze sites of involvement and candidal status of patients in a retrospective study.Study Design. Reticulation/keratosis, erythema, and ulceration (REU) scores and numerical rating scale (NRS) for pain were used. Correlation was tested using Spearman rank correlation, and the change in REU and NRS scores using the paired t test.Results. One hundred fifteen patients were evaluable with 55 follow-up visits. Pain showed positive correlation with the total weighted score (r = .40), erythema (r = .35), ulceration (r = .31), and reticulation scores (r = .29), all at P < .005. There was improvement in REU and NRS scores before versus after treatment (P < .0001). The internal consistency reliability analysis yielded good reliability with Cronbach coefficient alpha of 0.70. The ventral tongue, floor of mouth, and soft palate were never the only sites affected. Candidal carriage was present in 24% of cases but candidiasis developed in only 10% of carriers.Conclusions. The REU system is easy to use, correlates with an NRS for pain, and reliably reflects improvement attributable to treatment. Ventral tongue, floor of mouth, and soft palate were sites of OLP only if other sites were involved and candidiasis did not always develop in patients who were carriers. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:75-82)OAIID:oai:osos.snu.ac.kr:snu2012-01/102/0000047106/1SEQ:1PERF_CD:SNU2012-01EVAL_ITEM_CD:102USER_ID:0000047106ADJUST_YN:YEMP_ID:A077052DEPT_CD:861CITE_RATE:1.457FILENAME:OLP-REU scoring-park-2012.pdfDEPT_NM:치의학과EMAIL:[email protected]_YN:YCONFIRM: