Objective
Glucocorticoids suppress the hypothalamic–pituitary–adrenal axis, which may lead to glucocorticoid‐induced adrenal insufficiency. The study aimed to investigate the prevalence of this state ...in patients with oral lichen planus treated with topical clobetasol propionate.
Methods
In this cross‐sectional study, 30 patients with oral lichen planus receiving long‐term (>6 weeks) clobetasol propionate gel 0.025% were invited to participate. Adrenal function was assessed by measuring morning plasma cortisol after a 48‐h withdrawal of clobetasol treatment. In patients with plasma cortisol <280 nmol/L, a cosyntropin stimulation test was performed.
Results
Twenty‐seven patients were included. Twenty‐one (78%) patients presented with plasma cortisol ≥280 nmol/L (range 280–570 nmol/L), and six (22%) <280 nmol/L (range 13–260 nmol/L). Five of these six patients underwent cosyntropin stimulation that revealed severe adrenal insufficiency in two patients (cortisol peak 150 nmol/L and 210 nmol/L) and mild adrenal insufficiency in three patients (cortisol peak 350–388 nmol/L).
Conclusion
In this study, approximately 20% of patients receiving intermittent topical glucocorticoid treatment for oral lichen planus had glucocorticoid‐induced adrenal insufficiency. It is essential for clinicians to be aware of this risk and to inform patients about the potential need for glucocorticoid stress doses during intercurrent illness.
Objective
The World Workshop on Oral Medicine VII chose the oral microbiome as a focus area. Part 1 presents the methodological state of the science for oral microbiome studies. Part 2 was guided by ...the question: What is currently known about the microbiome associated with oral squamous cell carcinoma and potentially malignant disorders of the oral mucosa?
Materials and Methods
A scoping review methodology was followed to identify and analyse relevant studies on the composition and potential functions of the oral microbiota using high‐throughput sequencing techniques. The authors performed searches in PubMed and EMBASE. After removal of duplicates, a total of 239 potentially studies were identified.
Results
Twenty‐three studies on oral squamous cell carcinoma, two on oral leukoplakia and four on oral lichen planus were included with substantial differences in diagnostic criteria, sample type, region sequenced and sequencing method utilised. The majority of studies focused on bacterial identification and recorded statistically significant differences in the oral microbiota associated with health and disease. However, even when comparing studies of similar methodology, the microbial differences between health and disease varied considerably. No consensus on the composition of the microbiomes associated with these conditions on genus and species level could be obtained. Six studies on oral squamous cell carcinoma had included in silico predicted microbial functions (genes and/or pathways) and found some similarities between the studies.
Conclusions
Attempts to reveal the microbiome associated with oral mucosal diseases are still in its infancy, and the studies demonstrate significant clinical and methodological heterogeneity across disease categories. The immense richness and diversity of the microbiota clearly illustrate that there is a need for additional methodologically comparable studies utilising deep sequencing approaches in significant cohorts of subjects together with functional analyses. Our hope is that following the recipe as outlined in our preceding companion paper, that is Part 1, will enhance achieving this in the future and elucidate the role of the oral microbiome in oral squamous cell carcinoma and potentially malignant disorders of the oral mucosa.
Advances in high‐throughput sequencing technologies have allowed for a rapid increase in knowledge about the human microbiome in both healthy and diseased states, which is expected to increase our ...understanding of multifactorial diseases. The World Workshop on Oral Medicine VII chose the microbiome as one of its topics of focus. Part 1 of this review provides updated knowledge in the field of microbiome research, describes the advantages and disadvantages of currently available sequencing technologies, and proposes a seven‐step “recipe” for designing and performing studies that is supported by contemporary evidence. Part 2 of this review in a companion paper discusses the results of high‐throughput sequencing studies published to date on the microbiota associated with oral mucosal diseases. The goal of this collective enterprise is to encourage more oral medicine specialists to become engaged in multidisciplinary collaborations to investigate the role of the microbiome in relation to oral diseases, which could potentially lead to enhanced diagnosis, risk assessment and treatment of these patients.
Background
White sponge nevus is a rare autosomal dominant disorder that affects the non‐keratinised stratified squamous epithelium. Mutations in the genes that encode mucosa‐specific keratin‐4 and ...keratin‐13 are strongly linked to the manifestation of white sponge nevus. This study involved mutational analysis of the genes encoding keratin‐4 and keratin‐13 in two Swedish families with white sponge nevus.
Methods
The diagnosis of white sponge nevus was based on disease history, clinical characteristics of the lesions and, in the majority of the cases, histopathological examination. Samples were collected from the affected buccal mucosa using buccal swabs. DNA was subsequently extracted and amplified using touchdown‐PCR. The keratin‐4 and keratin‐13 genes were sequenced, and a genetic analysis was performed.
Results
A novel heterozygous missense mutation was identified in exon 1A of the keratin‐4 gene in Family 2. In addition, previously reported heterozygous missense mutations were identified in the keratin‐4 (E449K, A72V, Q156R, R208H) and keratin‐13 (L115P) genes in both families.
Conclusion
We describe a novel heterozygous missense mutation in the keratin‐4 gene of a Swedish family with white sponge nevus. Our results support the notion that mutations in keratin‐4 and keratin‐13 are the underlying cause of white sponge nevus.
Nonsense mutations, resulting in a premature stop codon in the open reading frame of mRNAs are responsible for thousands of inherited diseases. Readthrough of premature stop codons by small molecule ...drugs has emerged as a promising therapeutic approach to treat disorders resulting from premature termination of translation. The aminoglycoside antibiotics are a class of molecule known to promote readthrough at premature termination codons. Gentamicin consists of a mixture of major and minor aminoglycoside components. Here, we investigated the readthrough activities of the individual components and show that each of the four major gentamicin complex components representing 92-99% of the complex each had similar potency and activity to that of the complex itself. In contrast, a minor component (gentamicin X2) was found to be the most potent and active readthrough component in the gentamicin complex. The known oto- and nephrotoxicity associated with aminoglycosides preclude long-term use as readthrough agents. Thus, we evaluated the components of the gentamicin complex as well as the so-called "designer" aminoglycoside, NB124, for in vitro and in vivo safety. In cells, we observed that gentamicin X2 had a safety/readthrough ratio (cytotoxicity/readthrough potency) superior to that of gentamicin, G418 or NB124. In rodents, we observed that gentamicin X2 showed a safety profile that was superior to G418 overall including reduced nephrotoxicity. These results support further investigation of gentamicin X2 as a therapeutic readthrough agent.
Objective To study the prevalence and profile of thyroid disease in a cohort of referred patients with oral lichen planus (OLP) in comparison with a random population sample and to examine the ...clinical characteristics of OLP patients with and without thyroid disease. Study Design Data from 1611 patients with OLP and 1615 patients from the general population were collected by using a standardized registration method. Patients with OLP using levothyroxine (OLP/levothyroxine+) were re-examined to collect information about existing OLP lesions and to confirm the thyroid disease diagnosis. The clinical characteristics of OLP lesions in this group were compared with those in an age- and gender-matched population of patients with OLP without a history of thyroid disease or levothyroxine medication (OLP/levothyroxine−). Results Nearly 11% (n = 170) of the patients with OLP were taking levothyroxine compared with 2.5% (n = 40) of the controls (multivariate odds ratio 2.99, 95% confidence interval 2.03-4.44; P < .0001). No difference was found in the thyroid disease profile between the groups. At the time of re-examination, patients with OLP/levothyroxine− displayed more erythematous OLP lesions and complained of more severe symptoms compared with the OLP/levothyroxine+ group ( P < .001). Conclusions The prevalence of thyroid disease in patients with OLP was significantly higher than in the general population. The OLP lesions of patients with concomitant thyroid disease have a different presentation over time, which indicates a specific subgroup of OLP.
The worldwide scarcity of psychiatrists makes the identification of the factors associated with the intention to choose this specialty an important issue. This study aims to evaluate the association ...between religious affiliation and the intention to choose psychiatry as a specialty among medical students from 11 Latin American countries. We conducted a cross-sectional, multi-country study that included first- and fifth-year students of 63 medical schools in 11 Latin-American countries between 2011 and 2012. The main outcome and measures were the intention to pursue psychiatry as a specialty over other specialties (yes/no) and religious affiliation (without: atheist/agnostic; with: any religion). A total of 8308 participants were included; 53.6% were women, and the average age was 20.4 (SD = 2.9) years. About 36% were fifth-year students, and 11.8% were not affiliated with any religion. Only 2.6% had the intention to choose psychiatry; the highest proportion of students with the intention to choose psychiatry was among students in Chile (8.1%) and the lowest among students in Mexico (1.1%). After adjusting for demographic, family, academic as well as personal and professional projection variable, we found that those who had no religious affiliation were more likely to report the intention to become a psychiatrist OR: 2.92 (95%CI: 2.14-4.00). There is a strong positive association between not having a religious affiliation and the intention to become a psychiatrist. The possible factors that influence this phenomenon must be evaluated in greater depth, ideally through longitudinal research.
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