A mechanistic linkage between oral lichen planus and autoimmune thyroid disease.

OBJECTIVE: To determine the levels of antithyroid antibodies and thyroid hormones in the sera of patients with oral lichen planus (OLP), and to quantify the expression of thyroid proteins in OLP lesions. SUBJECTS AND METHODS: Venous blood samples were drawn from 110 patients with OLP who had no history of thyroid disease or levothyroxine supplementation (OLP+/LT4 -). A random population sample of 657 healthy subjects was used as the control group. Two additional groups were used as comparators. Immunohistochemical and qPCR analyses were performed on tissue specimens collected from the patients with OLP and thyroid disease and healthy subjects. RESULTS: No association was found between the presence of antithyroid antibodies and OLP. More patients in the OLP+/LT4 - group showed high levels of thyroid-stimulating hormone and low levels of free thyroxine than were seen in the control group. Thyroid-stimulating hormone receptor was more highly expressed in the OLP lesions of patients with thyroid disease than in the healthy oral mucosa. CONCLUSIONS: A significant number of patients with OLP who are not previously diagnosed with thyroid disease have thyroid parameters that are compatible with hypothyroidism. The expression of thyroid-stimulating hormone receptor in OLP lesions suggests that mechanisms related to autoimmune thyroid disease are involved in the aetiology of OLP.

Oral psoriasis-a diagnostic dilemma: a report of two cases and a review of the literature.

Whether psoriasis can manifest itself in the oral mucosa has been a matter of debate for many years. If an oral version of psoriasis exists, most researchers regard this manifestation as rare. The present report describes two patients who presented with lesions possibly related to cutaneous psoriasis. One patient had patchy erythematous lesions on the gingiva, and one had serpiginous lesions in the hard palate. We discuss these cases in relation to the existing literature, with special emphasis on the clinical and histopathologic criteria for the diagnosis of oral psoriasis.

Use of systemic medication in patients with oral lichen planus - a possible association with hypothyroidism.

BACKGROUND: Several drugs have been regarded as a possible aetiological factor for oral lichen planus (OLP). OBJECTIVE: To investigate the medication profile of patients with OLP and its possible association with the pathogenesis of OLP. METHODS: Data from 956 patients with OLP and 1029 controls were collected using a standardized registration method. All regular medications were recorded and classified according to the Anatomical Therapeutic Chemical Classification System. RESULTS: Patients with OLP used thyroid preparations (P < 0.001) and non-steroidal anti-inflammatory drugs (NSAIDs) (P < 0.01) in higher proportions compared to controls. A multivariate logistic regression model demonstrated that levothyroxine was associated with OLP (multivariate OR 3.39, 95% CI: 2.09-5.46, P < 0.001), even after controlling for confounders, including age, sex, smoking, allergies and systemic diseases. No statistical significance could be found between NSAIDs and OLP using the same model. CONCLUSION: In this study, the use of levothyroxine was associated with OLP, which in turn suggests a possible connection with hypothyroidism.

Advancing oral medicine through informatics and information technology: a proposed framework and strategy.

The implementation of information technology in healthcare is a significant focus for many nations around the world. However, information technology support for clinical care, research and education in oral medicine is currently poorly developed. This situation hampers our ability to transform oral medicine into a 'learning healthcare discipline' in which the divide between clinical practice and research is diminished and, ultimately, eliminated. This paper reviews the needs of and requirements for information technology support of oral medicine and proposes an agenda designed to meet those needs. For oral medicine, this agenda includes analyzing and reviewing current clinical and documentation practices, working toward progressively standardizing clinical data, and helping define requirements for oral medicine systems. IT professionals can contribute by conducting baseline studies about the use of electronic systems, helping develop controlled vocabularies and ontologies, and designing, implementing, and evaluating novel systems centered on the needs of clinicians, researchers and educators. Successfully advancing IT support for oral medicine will require close coordination and collaboration among oral medicine professionals, information technology professionals, system vendors, and funding agencies. If current barriers and obstacles are overcome, practice and research in oral medicine stand ready to derive significant benefits from the application of information technology.

Oral pigmentation in the hard palate associated with imatinib mesylate therapy: a report of three cases.

Imatinib mesylate is a tyrosine kinase inhibitor which targets Bcr-Abl-protein, c-Kit, and platelet-derived growth factor receptor. The drug was originally developed for treatment of chronic myeloid leukemia but is also regarded as first-line treatment of patients with metastatic gastrointestinal stromal tumours (GIST). Dermatologic side effects are common, with superficial edema and rash as the most frequent. In addition, imatinib mesylate treatment is often associated with hypopigmentation. Intraoral side effects are very rare. The present paper demonstrates 1 patient with GIST and 2 patients with chronic myeloid leukemia treated with imatinib mesylate for 5-6 years. All 3 patients presented with diffuse solitary bluish-brown pigmentations in the hard palate. The lesions persisted at follow-ups. There were no other pigmentations in the oral mucosa. The histopathologic examination showed depositions of melanin pigment in the lamina propria. The possible relationship between the observed melanotic maculae and imatinib mesylate treatment is discussed.

Molecular characterization of uptake hydrogenase in Frankia.

A molecular characterization of uptake hydrogenase in Frankia was performed by using two-dimensional gel electrophoresis, matrix-assisted laser-desorption ionization-time-of-flight mass spectrometry, PCR amplification and Southern blotting. A polypeptide of approx. 60 kDa was recognized in Frankia UGL011102, AVCI1 and KB5 on the two-dimensional gel by blotting with Ralstonia eutropha (Hox G) antibody. Further analysis by MS resulted in a peptide 'fingerprint', which was similar to the membrane-bound hydrogenase 2 large subunit (HYD2) in Escherichia coli. In addition, a 127 bp PCR fragment could also be amplified from Frankia AVCI1, which gave a 76% similarity with the large subunit of hydrogenase in, e.g., Azotobacter chrococcum, Bradyrhizobium japonicum and Rhizobium leguminosarum. Although immunological similarity between the small subunit of Frankia hydrogenase and that of other organisms has not yet been found, a PCR product of 500 bp could be amplified from the local source of Frankia, the analysis of which gave 69 and 67% identity with the small subunit of hydrogenases in B. japonicum and R. leguminosarum respectively. A Southern-blot analysis further indicated evidence for the presence of the small hydrogenase subunit in other Frankia strains, i.e. KB5, AvcI1 and CcI3.

Frankia KB5 possesses a hydrogenase immunologically related to membrane-bound.

The immunological relationship of the hydrogenase in Frankia KB5 to hydrogenases in other microorganisms was investigated using antisera raised against holo-[NiFe]-hydrogenases isolated from Alcaligenes latus, Azotobacter vinelandii, Ralstonia eutropha, and the small and large hydrogenase subunits from Bradyrhizobium japonicum. The antisera raised against the A. latus, R. eutropha, and B. japonicum (large subunit) polypeptides were found to recognize two polypeptides, corresponding to the unprocessed and processed forms of the hydrogenase subunit in Frankia KB5. None of the antisera, including the antibodies produced against the small hydrogenase subunit isolated from B. japonicum, recognized any polypeptide related to the small hydrogenase subunit in Frankia KB5. An immunogold localization study of the intracellular distribution of hydrogenase in Frankia KB5, with the cryo-section technique, showed that labeling in the membrane of both hyphae and vesicles was positively correlated with hydrogenase activity.

Intravenous lidocaine infusion in the treatment of experimental human skin burns - digital colour image analysis of erythema development.

Previous studies have shown that local anaesthetics possess a wide range of effects on the pathophysiology of burns, including inhibition of burn oedema and inhibition of progressive burn ischemia. The present randomised double-blind cross-over study in six volunteers investigated the effects of intravenous lidocaine infusion on partial thickness skin burns. A thermoprobe was used to induce a standardised thermal injury (1 cm(2)) on the flexor side of one forearm and was repeated on the opposite side 1 week later. Subjects received either an intravenous bolus dose of lidocaine (1 mg kg(-1)) immediately after the thermal trauma followed by continuous intravenous infusion of lidocaine (40 microg kg(-1) min(-1)) during 4 h or equal volumes of isotonic saline. Macrophotographs of the experimental skin area were taken preburn and 1, 2, 3, 4, and 12 h postburn and evaluated by computerised image colour analysis using normalised rgb (n-rgb) and Hue-Saturation-Intensity (HSI) colour systems as a quantitative measure of pathophysiological events. Maximum erythema occurred 2-3 h postburn. Differences between lidocaine- and placebo-treated burns were not significant during the first 4 h postburn. At 12 h postburn, the lidocaine-treated burn demonstrated a significantly faster restitution of residual erythema compared to control sites. The present study shows that intravenous lidocaine significantly inhibits the long-term inflammation-induced tissue responses to thermal trauma.

Importance of nitric oxide in the regulation of burn oedema, proteinuria and urine output.

Burn injuries trigger a pronounced inflammatory response in the burned skin, resulting in oedema formation and impaired circulation. This response involves activation of the nitric oxide (NO) synthetic pathway, which could play a key role in the complex hemodynamic and hemostatic changes occurring as a result of a burn trauma. The results presented in full-thickness skin burns of rats show that the NO-precursor, L-arginine (n = 10), inhibit burn-induced plasma extravasation as compared to saline-treated burned controls (n = 10) (p<0.001) to a level not significantly different from nonburned animals. Administration of the NO-synthase inhibitor. NG-nitro-L-arginine (L-NNA) (n = 10), did not significantly influence burn extravasation compared to burned controls. Accumulated urine volume 90 min post-burn increased ten-fold in burned animals treated with L-arginine compared to saline-treated burned controls (p<0.001) and nonburned animals (p<0.001), while L-NNA had no significant effect on diuresis. A significantly increased proteinuria occurred in L-arginine treated burned animals as compared to burned controls and nonburned controls (p<0.001), whereas L-NNA did not significantly influence the leakage of protein in the urine. Activation of NO synthesis significantly suppresses burn edema and strongly increases diuresis along with increased proteinuria.

Role of nitric oxide in the control of burn perfusion.

Vascular changes following deep skin burns are characterised by vasoconstriction and progressive ischemia. Nitric oxide (NO) has been shown to be a potent regulator of vascular smooth muscle tone and tissue perfusion. We assessed the importance of NO on post-burn skin perfusion in rats using laser Doppler. The present results show that neither the NO-synthase inhibitor, NG-nitro-L-arginine (L-NNA) (n = 6) nor the NO precursor, L-arginine, significantly influenced skin perfusion in nonburned skin compared to saline-treated animals. In the area of full-thickness skin burn, neither L-arginine (n = 6) nor L-NNA (n = 6) had significant influence on post-burn perfusion compared to saline-treated controls (n = 6). Administration of L-NNA (n = 6) significantly impaired skin perfusion in the area adjacent to the contact burn representing a partial-thickness burn, while the NO precursor, L-arginine (n = 6) had no significant effect on burn perfusion as compared to saline-treated controls (n = 6). In conclusion, impairment of perfusion in a full thickness burn following administration of NO-synthase inhibitor suggests that nitric oxide is involved in the mechanisms responsible for maintaining adequate circulation post-burn. The lack of additional improvement of perfusion in response to L-arginine may suggest that NO synthesis in response to the thermal trauma is already at a peak.

Hydrogenase in Frankia KB5: expression of and relation to nitrogenase.

The localization and expression of the hydrogenase in free-living Frankia KB5 was investigated immunologically and by monitoring activity, focusing on its relationships with nitrogenase and H2. Immunological studies revealed that the large subunit of the hydrogenase in Frankia KB5 was modified post-translationally, and transferred into the membrane after processing. The large subunit was constitutively expressed and no correlation was found between hydrogenase activity and synthesis. Although H2 was not needed for induction of hydrogenase synthesis, exogenously added H2 triggered hydrogen uptake in medium containing nitrogen, i.e., in the hyphae. A correlation between nitrogenase activity and hydrogen uptake was found in cultures grown in media without nitrogen, but interestingly the two enzymes showed no co-regulation.

Digital image analysis of erythema development after experimental thermal injury to human skin: effect of postburn topical local anesthetics (EMLA).

UNLABELLED: Local anesthetics inhibit edema and improve circulation in experimental burns. We evaluated the effect of topical local anesthetics on human skin burns in volunteers using computerized color analysis that allowed repeated noninvasive quantitative measurements. A standardized partial-thickness burn (1 cm2) was induced in one forearm of 10 healthy volunteers and in the opposite forearm a week later. The burned areas were treated with lidocaine/prilocaine cream (EMLA; Astra, Sweden) or a placebo cream for 1 h. The experimental skin area was photographed before and 1, 2, 4, and 12 h postburn. Digitized images were evaluated using normalized red-green-blue and Hue-Saturation-Intensity. Differences in erythema between skin treated with EMLA and placebo were not significant during the first 4 h postburn. However, 12 h postburn, a pronounced decrease in the degree of erythema was observed in EMLA-treated skin compared with placebo-treated skin. We conclude that topical local anesthetics administered for 1 h postburn significantly reduces the duration of erythema after a mild thermal injury, which suggests a potential use in clinical practice in the treatment of minor skin burns. IMPLICATIONS: Burn injury constitutes a serious type of tissue damage that activates inflammatory mechanisms, often causing pain, disfiguration, or malfunction. We treated burns using an anesthetic cream and demonstrated a reduction in burn-induced inflammation by using computer-based color image analysis.

Topical local anaesthetics (EMLA) inhibit burn-induced plasma extravasation as measured by digital image colour analysis.

Amide local anaesthetics have previously been shown to reduce oedema and improve dermal perfusion following experimental burns. Previous studies have used invasive techniques for burn oedema quantification which do not allow continuous monitoring in the same animal. The present study used digital image colour analysis to investigate the effect of topical local anaesthetics on burn-induced extravasation of Evans blue albumin. A standardised full-thickness burn injury (1 x 1 cm) was induced in the abdominal skin of anaesthetised rats. The burn area was subsequently covered with 0.5 g of lidocaine-prilocaine cream 5% (25 mg of each in 1 g; EMLA, ASTRA, Sweden) or placebo cream during the first hour post-burn. One hour after the burn trauma, animals received Evans blue dye intravenously. Skin colour appearances were recorded by macrophotography before the burn and 5, 60. 65, 90, 120, 150, and 180 min post-burn. Colour slides were digitised and colour changes were analysed using the normalised red-green-blue (n-rgb) colour system. Results showed a significant inhibition of Evans blue extravasation between 60 and 180 min post-burn in EMLA-treated animals versus controls. Topical local anaesthetics are potent inhibitors of burn-induced plasma albumin extravasation, probably by direct action on vascular permeability and by inhibition of various steps of the pathophysiological response after burn injury.

Quantification of burn induced extravasation of Evans blue albumin based on digital image analysis.

The present study evaluated a non-invasive method based on digital image colour analysis that allows near-continuous quantification of extravasated Evans blue albumin after burn injury. A full-thickness burn was induced in the abdominal skin of rats, followed by injection of Evans blue dye. Tissue content of Evans blue were quantified using spectrophotometry, and compared with digital colour analysis. The non-invasive technique demonstrated a good correlation when compared to invasive spectrophotometry, but is superior by allowing near continuous measurement in the same subject and may be of value for evaluation of effective burn oedema-reducing treatment.

Inhibition of plasma extravasation after burns by D-myo-inositol-1,2,6-trisphosphate using digital image colour analysis.

D-myo-inositol-1,2,6-triphosphate (1,2,6-IP3) has beneficial effects in experimental, progressive burn-induced ischaemia and oedema. A 1 cm2 full-thickness burn was made in the skin of 20 rats with a hot aluminium rod followed by infusion of 1,2,6-IP3 (60 mg.kg.-1 h-1) or isotonic saline (n = 10 in each group). One hour later Evans blue was injected intravenously. Colour photographs of the area of the burn were taken in a standard manner before the burn and at intervals for three hours afterwards. The photographs were analysed by digital image colour analysis using normalised red-green-blue values. The increase in normalised blue values between 60 and 180 minutes after the burn was significantly reduced in animals treated with 1,2,6-IP3 compared with control animals (p < 0.001). Spectrophotometric analysis of extravasated Evans blue in the skin 180 minutes after the burn showed that it had been significantly inhibited by treatment with 1,2,6-IP3 (p < 0.001). In conclusion, digital image analysis allowed repeated evaluation over time and confirmed previous data about the ability of 1,2,6-IP3 to inhibit extravasation of plasma after burns.

Assessment of erythema and skin perfusion by digital image analysis and scanner laser Doppler.

BACKGROUND/AIMS: In the present study, a model for measuring the intensity of skin erythema by computer-assisted digital image analysis (DIA) was elaborated. The DIA technique was compared with laser Doppler perfusion imaging (PIM) to evaluate the relationship between erythema and skin perfusion. METHODS: To produce erythema, three different types of nicotine patches (Nicotinell®, Nicorette® and Nicorette® placebo) were randomly applied ventrally on the upper arms for the time period recommended by the manufactures. After removal of the patches, colour photographs for subsequent DIA were taken and laser Doppler scanning for PIM was performed. The relationship between PIM and DIA was estimated intra- and inter-individually. RESULTS/CONCLUSIONS: A statistically significant linear correlation between PIM and DIA data was found, but the relationship was relatively weak. This may be explained by the fact that DIA and PIM are influenced by different physiological factors such as skin chromophores and velocity of moving cells. The results strengthen the theory that erythema and perfusion measurements reflect separate physiological phenomena and that the methods should be considered complements to each other in the experimental situation.

Digital image analysis (DIA) of colour changes in human skin exposed to standardized thermal injury and comparison with laser Doppler measurements.

Clinical macrophotography followed by digitization and computer-assisted image analysis was performed on volunteers exposed to a mild experimental thermal injury. The aim was to elaborate a non-invasive technique allowing repetitive and quantitative monitoring of induced erythema and to evaluate a possible relationship with laser Doppler measurement of skin perfusion. A standardized 1 x 1 cm large thermal trauma was induced in the skin of the ventral forearm of 12 volunteers. Photographic recordings and skin blood flow measurements were made preburn and at 30-min, 1-h, 2-h, 4-h and 12-h postburn. Image analysis was performed with two colour systems, normalized rgb-values (rgb) and Hue-Saturation-Intensity (HSI). Erythema measured by rgb and HSI was most pronounced during the first hour postburn, after which it gradually decreased in order to increase again at 12 h postburn. Skin perfusion peaked at 30 min postburn and then continuously decreased during the course of the experiments. Degree of erythema could be quantified using both colour systems and a linear relationship was obtained between the observed colour changes of both systems and changes in skin perfusion. Results may also indicate that erythema can be present without a concomitant increase in skin perfusion, probably representing postburn venous stasis. The present study showed that digital image analysis is a non-invasive technique allowing repetitive and quantitative analysis of skin erythema which can be used to monitor pathophysiological changes in the body as well as the result of their treatment.

Healing of lichenoid reactions following removal of amalgam. A clinical follow-up.

174 patients referred to the Department of Oral and Maxillofacial Surgery, Central Hospital, Karlstad, Sweden during 1987 to 1989 for lichenoid lesions and evaluation of a possible connection with amalgam restorations were invited to a clinical re-examination. 159 of the patients were re-examined with the purpose of evaluating the long-term effect upon performed substitution therapy. Partial or total removal of amalgam had been recommended according to a set of given criteria. The re-examination showed that 62 patients had performed partial and 69 patients total removal of amalgam fillings. 28 patients had not performed any substitution therapy. There was a difference between recommended and performed therapy. The results demonstrated that 92% of patients with lichenoid lesions only in contact with amalgam fillings healed or improved clinically following removal of amalgam. No statistical difference was found in healing between patients who only removed fillings in contact and those who had removed all amalgam restorations. More than 60% of buccal lichenoid lesions without contact with amalgam at time of referral disappeared following amalgam substitution. Gingival lichenoid lesions did not respond to substitution of amalgam to another material. 3 out of 17 patch-tested patients demonstrated a hypersensitivity reaction to mercury. All lichenoid lesions in these patients healed following total substitution. Partial or total removal of amalgam fillings was also performed on 10 patients with completely negative patch-tests. 6 out of these patients demonstrated complete healing of their lichenoid reactions at re-examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of computer-assisted image analysis for noninvasive evaluation of oral lichenoid reactions and oral leukoplakia.

The objective of the present study was to elaborate and to evaluate a method in which the clinical appearance of a mucosal lesion could be expressed by means of color and morphologic features extracted from digitized images. The ability to express mucosal changes with image features was evaluated, as was the accuracy of a classification of the lesions on the basis of image feature analysis. Computer-assisted image analysis was performed on digitized color slides from 76 patients with lichenoid reactions that included both oral lichen planus and contact lesions and 20 patients with homogenous oral leukoplakia. Color features were measured according to the intensity-hue-saturation color system, and morphologic features were estimated by tracing the hyperkeratotic area. Hyperkeratinizing and inflammatory tissue reactions could be demonstrated and defined by image analysis. Image features indicating inflammatory tissue reactions were more pronounced in cases of oral lichenoid reactions. Morphologic parameters could express the anatomic appearance of the lesions. The comparison between histopathologic diagnosis and a classification through computerized analysis demonstrated that 90.5% of oral lichenoid reactions could be separated from homogenous oral leukoplakia by linear discriminant analysis.