[The use of photodynamic therapy in patients with severe forms of leukoplakia]. / Primenenie fotodinamicheskoi terapii u patsientov s tyazhelymi formami leikoplakii.

OBJECTIVE: The aim the study is to increase the effectiveness of the treatment of severe forms of leukoplakia with the use of photodynamic therapy. MATERIAL AND METHODS: 120 patients with severe forms of leukoplakia were examined. 30 patients were diagnosed with Cr and carcinoma in situ, and therefore they were excluded from the study. In 90 patients, the diagnosis was confirmed by histological and IHC studies. Before the use of photodynamic therapy, the degree of saturation of pathological foci with a photosensitizer was determined by the method of fluorescent diagnostics using the LED device «RFS-400¼. RESULTS: As a result of treatment with photodynamic therapy using a 2nd generation photosensitizer («Photoditazine¼ 0.5% gel penetrator), a significant improvement in the epithelization of lesion elements was observed: in 92% of patients with verrucous leukoplakia and in 83% of patients with erosive leukoplakia. CONCLUSION: The use of photodynamic therapy for the treatment of patients with complicated forms of leukoplakia is an effective method of treatment for this pathology.

Adverse Drug Events in the Oral Cavity.

Adverse reactions to medications are common and may have a variety of clinical presentations in the oral cavity. Targeted therapies and new biologic agents have revolutionized the treatment of cancers, autoimmune diseases, and inflammatory and rheumatologic diseases but have also been associated with adverse events in the oral cavity. This review describes the most common clinical presentations of oral mucosal reactions to medications, namely hyposalivation, lichenoid reactions, ulcers, bullous disorders, pigmentation, fibrovascular hyperplasia, reactive keratosis, dysesthesia, osteonecrosis, infection, angioedema, and malignancy.

Oral mucosal health in liver transplant recipients and controls.

Immunosuppressive drugs and other medications may predispose patients to oral diseases. Data on oral mucosal health in recipients of liver transplantation (LT) are limited. We, therefore, recruited 84 LT recipients (64 with chronic liver disease and 20 with acute liver failure) for clinical oral examinations in a cross-sectional, case-control study. Their oral health had been clinically examined before transplantation. The prevalence of oral mucosal lesions (OMLs) was assessed in groups with different etiologies of liver disease and in groups with different immunosuppressive medications, and these groups were compared to controls selected from a nationwide survey in Finland (n = 252). Risk factors for OMLs were evaluated with logistic regression. OMLs were more frequent in LT recipients versus controls (43% versus 15%, P < 0.001), and the use of steroids raised the prevalence to 53%. Drug-induced gingival overgrowth was the single most common type of lesion, and its prevalence was significantly higher for patients using cyclosporine A (CSA; 29%) versus patients using tacrolimus (TAC; 5%, P = 0.007); the prevalence was even higher with the simultaneous use of calcium channel blockers and CSA (47%) or TAC (8%, P = 0.002). Lesions with malignant potential such as drug-induced lichenoid reactions, oral lichen planus-like lesions, leukoplakias, and ulcers occurred in 13% of the patients with chronic liver disease and in 6% of the controls. Every third patient with chronic liver disease had reduced salivary flow, and more than half of all patients were positive for Candida; this risk was higher with steroids. In conclusion, the high frequency of OMLs among LT recipients can be explained not only by immunosuppressive drugs but also by other medications. Because dry mouth affects oral health and OMLs may have the potential for malignant transformation, annual oral examinations are indicated.

Rise and fall of oral health products with Canadian bloodroot extract.

The rhizome of Sanguinaria canadensis (SC, bloodroot) contains an active principle with antimicrobial, antiinflammatory, antioxidative and immunomodulatory effects. For this reason SC extract has been added to toothpastes and mouthwashes in various concentrations. When tested separately, neither the toothpastes nor the mouthwashes with SC extract had any demonstrable clinical effectiveness against dental plaque and gingivitis. Although using them together twice a day seemed more effective than using placebo, more recent studies have shown conflicting results. Preclinical safety studies up to 2000, which did not include studies longer than 6 months, were thought not to indicate any appreciable potential for harm - to the oral mucosa in particular. In 2003, the FDA Subcommittee on Oral Health Care Drug Products for Over-the-Counter Human Use concluded from a review that using SC-containing products is safe. However, for reasons unknown, the review failed to consider publications between 1999 and 2001 that suggested a possible link between the use of SC-containing products and the pre-neoplastic lesion, leukoplakia. As it happened, bloodroot had already been removed (in 2001) from the formula of one of the most widely used products in question and the brand has since then disappeared altogether from the worldwide market.

Reference moist smokeless tobacco-induced apoptosis in human monocytes/macrophages cell line MM6.

Moist smokeless tobacco use is associated with various types of oral injury, including leukoplakia and dipper's pouch, although the mechanism by which the injury is caused still remains unclear. One possible mechanism is that moist smokeless tobacco affects the inflammatory response. For example, a study by Johnson et al. demonstrated a reduction in the volume density of macrophages and increased inflammation and redness at the smokeless tobacco placement site when compared to non-placement site. The current study investigated the direct effect of reference moist smokeless tobacco extract (STE) exposure on the viability of MM6 monocyte/macrophage cell line. The exposure of MM6 cells to various concentrations of STE, led to a significant and dose-related decrease in cell viability. Furthermore, STE exposure resulted in an increase in Annexin V/PI positive cells, an increase in TUNEL-positive cells, and cleaved PARP staining all of which were inhibited by pre-incubation with a pan-caspase inhibitor, suggesting that the observed STE toxicity was due to the induction of apoptosis. Next, the role of various moist smokeless tobacco-derived components in STE-induced apoptosis of MM6 cells was investigated. Our findings suggest that STE-induced osmotic stress, but not exposure to nicotine, plays an important role in STE-induced apoptosis of MM6 cells. Together, these data show for the first time that STE exposure leads to the induction of apoptosis in human monocyte/macrophage cells, which appears to be induced in part, by reference STE-mediated osmotic stress.

Oral manifestations of habitual khat chewing: a case-control study.

BACKGROUND AND OBJECTIVES: Khat, or qat (Catha edulis), is a shrub indigenous to Yemen and certain parts of eastern Africa. Chewing the leaves, which have sympathomimetic and euphoric effects, is a popular habit in numerous countries including the Yemenite population in Israel. Khat has potentially significant toxic effects; however, its oral effects have been only sporadically examined and some changes suggested. The aim of this study was to assess the association between habitual Khat use and oral/dental pigmentation, gingival health, and reports of oral dryness. STUDY DESIGN: Forty-seven Yemenite Israeli individuals >30 years old, who chewed Khat at least twice a week for over 3 years, and 55 control subjects were studied. All individuals underwent standard clinical oral examinations for color changes and gingival health. RESULTS: White changes were significantly more prevalent in the khat chewers, identified primarily at the chewing site (83% vs. 16%). The difference in the prevalence of oral mucosal pigmentation between nonchewing nonsmoking (66.7%) and the khat-chewing (100%) groups was highly significant. The mean gingival index and the depth of periodontal pockets of the khat-chewing subjects were significantly reduced at the chewing side compared with the nonchewing side. Increased gingival recession was recorded on the khat-chewing side. Discoloration of the teeth adjacent to the site of chewing was recorded. Oral dryness occurring 30 minutes after initiating the khat-chewing session was reported by khat users. CONCLUSION: Khat chewing may result in a number of changes in the oral mucosa and the dentition. The mechanical and chemical irritation may result in the development of mucosal white lesions and dark pigmentation. Khat chewing may reduce aspects related to risk of gingival and periodontal inflammation, but it appears to be associated with attachment loss at the site of chewing.

Exposure to alcohol or tobacco affects the pattern of maturation in oral mucosal cells: a cytohistological study.

OBJECTIVE: To assess the maturation pattern of oral mucosal cells of patients exposed to tobacco and alcohol. METHODS: (i) Group without lesions. Smears obtained from the lower lip, border of the tongue and floor of the mouth of 31 control individuals (group I), 49 tobacco users (group II) and 27 tobacco/alcohol users (group III) were stained using the Papanicolaou method. The first 100 cells counted on each smear determined the maturation pattern and the keratinization index (KI). Analysis of variance (ANOVA) and the Tukey multiple comparison test were used for statistical analysis, at a 5% significance level. (ii) Group with lesions. Cytopathological and histopathological studies were conducted for 15 patients: eight with leucoplakia without epithelial dysplasia, two with epithelial dysplasia and five with squamous cell carcinoma. RESULTS: (i) Group without lesions. Statistical analysis revealed a smaller number of superficial cells with nuclei in all sites of the group of tobacco/alcohol users (group III) when compared to the control group (group I), and this difference was statistically significant (P<0.005). (ii) Group with lesions. The severity of histopathological findings increased with the increase in the number of cells of the deeper epithelial layers, with a statistically significant difference in the number of intermediate (P=0.013) and parabasal cells (P=0.049), which increased with the severity of the epithelial maturation disorder: leucoplakias with dysplasia had a greater number of intermediate and parabasal cells than leucoplakias without dysplasia; and the number in squamous cell carcinomas was greater than in leucoplakias with dysplasia. CONCLUSION: The maturation pattern of cells in the three anatomic sites showed changes that may be associated with the synergistic effect of tobacco and alcohol. Also, the severity of histopathological findings was associated with the increase in the number of cells in the deeper epithelial layers.

Exacerbation of oral erosive lichen planus by combination of interferon and ribavirin therapy for chronic hepatitis C.

Hepatitis C virus (HCV) induces extrahepatic manifestations such as oral lichen planus (OLP) as well as chronic liver diseases. The treatment of HCV-related chronic liver disease has evolved from the use of a single agent, mainly interferon (IFN), to the combination of IFN and ribavirin. We present a case of erosive OLP, cutaneous lichen planus (CLP), and leukoplakia of the vocal cord in a man with chronic hepatitis C infection treated with IFN and ribavirin. A 65-year-old man suffered from OLP before undergoing combination of IFN and ribavirin therapy for chronic hepatitis C. He was initially treated with IFNbeta (6 million units (MU) /day for 2 weeks), then a combination of IFNalpha-2b (6 MU/day for 2 weeks and 3 times a week for 14 weeks) and ribavirin (400-600 mg/day). The OLP lesion was not aggravated by application of steroids during the 7 weeks after the treatment, but after 18 weeks, the combination of IFN and ribavirin was stopped because of aggravation of the OLP. Elevated aminotransferase levels returned to normal during the therapy. But 7 weeks after discontinuation, aminotransferase levels rose to 10 times the normal range. Five months after discontinuation, the papules of CLP appeared. Eight months after discontinuation, the OLP erosion had gradually reduced, but some erosion remained. Aminotransferase levels were decreased, but serum HCV RNA had not disappeared. Caution should be exercised when IFN or ribavirin therapy is given to chronic hepatitis C patients with prior erosive OLP.

Laryngeal findings in users of combination corticosteroid and bronchodilator therapy.

EDUCATIONAL OBJECTIVE: At the conclusion of this article, the readers should be able to 1) describe the laryngeal findings in patients who use combination therapy for asthma, 2) discuss the mechanism of laryngeal irritation from the use of inhalers, and 3) describe possible mechanisms for reducing laryngeal irritation and secondary dysphonia from the use of inhalers. OBJECTIVES: To describe voice changes and laryngeal findings in patients who are started on combination corticosteroid and bronchodilator therapy in the form of a dry powder inhaler (DPI). STUDY DESIGN: Retrospective, single-subject design. METHODS: Retrospective review of 10 consecutive patients meeting inclusion criteria, who presented at the voice center with more than 4 weeks of dysphonia after being started on a combination form of asthma medication for control and maintenance therapy. All patients were nonsmokers and without history of previous identification or excision of vocal pathology. All patients were treated previously with a proton pump inhibitor for gastroesophageal reflux. Laryngeal videostroboscopic evaluations were performed on all patients. Patients were asked to complete a questionnaire regarding their perceived voice change and history of medical maintenance therapy for asthma. RESULTS: Dysphonia was present in the patients selected for greater than 4 weeks. Patients had been switched to combination therapy after previously using traditional two-drug asthma regimens. In eight of nine patients, the vocal folds demonstrated areas of hyperemia, with plaque-like changes on the surface mucosa. Reduced amplitude of vibration and a reduction in mucosal wave propagation were present on videostroboscopy. Questionnaires revealed that all patients were initiated on combination DPI treatment within the last 6 months. CONCLUSIONS: Dysphonia caused by a change in the surface mucosa is a side effect from the use of DPI therapy for asthma. The high-impact force during inhalation of the medication and carrier leads to deposition of particles in the upper airway. We believe the extent of mucosal irritation can be minimized by patient education in the proper delivery of DPI. In some cases, however, return of the two medications delivered separately was necessary. The irritation of the laryngeal mucosa and return of normal vibratory parameters occurred in all patients.

Specific induction of the high-molecular-weight microtubule-associated protein 2 (hmw-MAP2) by betel quid extract in cultured oral keratinocytes: clinical implications in betel quid-associated oral squamous cell carcinoma (OSCC).

Betel quid (BQ) chewing, a popular habit in numerous Asian countries including India and Taiwan, has a strong correlation with an increased risk of oral squamous cell carcinoma (OSCC). While substantial efforts have been made to test the cytotoxic, genotoxic and mutagenic effects of BQ extract and its components, the disease mechanisms underlying BQ-induced oral carcinogenesis remain obscure. Here, we show that a neuronal protein, microtubule-associated protein 2 (MAP2), was induced by BQ extract in cultured normal human oral keratinocytes (NHOKs). Subsequent analyses demonstrated that such induction was more eminent and consistent in the high-molecular-weight isoform of MAP2 (hmw-MAP2) than that in its low-molecular-weight counterpart (lmw-MAP2). Furthermore, we analyzed expression of hmw-MAP2 protein in 88 oral specimens consisting of clinicopathologically pre-malignant (leukoplakia) and malignant (OSCC) lesions, along with their adjacent normal mucosa. Immunohistochemistry revealed that, with the exposure to BQ, the hmw-MAP2 was over-expressed in 41.2% (7/17) of OSCC, 11.2% (1/9) of leukoplakia and none (0/19) of normal mucosa. In contrast, expression of the hmw-MAP2 was barely detected in BQ-free OSCC. These results suggest a significant correlation between expression of the hmw-MAP2 and BQ-associated progression of oral carcinogenesis (P=0.0046). Interestingly, the hmw-MAP2 was found to preferentially express in histopathologically less differentiated OSCC (P=0.014); the percentages of positive staining in poorly, moderately and well differentiated OSCC were 62.5, 21.4 and 7.1%, respectively. However, BQ chewing appeared to have marginal correlation with such propensity. Finally, we show that the majority of hmw-MAP2-positive poorly differentiated lesions were also histopathologically invasive. Taken together, these findings suggest the possibility that the hmw-MAP2 may be a diagnostic marker for BQ-chewing lesions and a potential therapeutic target. To our knowledge, this study has provided the first clinical implication that closely links a cytoskeletal protein to BQ-associated oral cancer.