The prevalence and distribution of human papillomavirus genotypes in oral epithelial hyperplasia: proposal of a concept

Background:  Evidence is accumulating for the aetiological role of human papillomavirus (HPV) in the pathogenesis of potentially malignant oral mucosal lesions and squamous cell carcinomas.
Methods:  Paraffin tissue sections from 49 patients with 'white patches' of the oral mucosa were investigated histologically, by broad-spectrum PCR followed by genotyping and chromogenic in situ hybridisation (CISH).
Results:  Histologically, 33 flat hyperplasias and 16 papillary hyperplasias were diagnosed. Twenty-two of 28 samples studied (78.6%) were positive for HPV DNA by PCR and six were negative. The following HPV types were detected in decreasing order of prevalence: HPV 35, HPV 6, HPV16, HPV 53, HPV 18, HPV 51 and HPV 55. Seventeen samples (60.7%) contained high-risk HPV DNA. Using CISH, ≥ 1 HPV signals were detected at least in a few epithelial cells in 95% of cases studied. All but one case were positive with the high-risk HPV probe and all HPV infections contained low viral load. Concordant positive results both by PCR and CISH were detected in 14 of 19 cases (73.7%) analysed.
Conclusions:  The high prevalence of HPV infection in hyperplastic 'white patches' of the oral mucosa supports the putative role of HPV at an early stage of oral carcinogenesis. These results further indicate that the majority of white oral mucosal lesions – flat, exophytic, wart-like or papillary proliferations – could be considered as the clinical manifestations of oral HPV infection. This finding has clinical relevance regarding therapy and patient management and may help in elucidating the role of HPV infection in oral carcinogenesis.     

Analysis of cytokine pattern in exhaled breath condensate of lung transplant recipients with bronchiolitis obliterans syndrome

Introduction  

Exhaled breath condensate (EBC) analysis is a promising method for investigating airway pathology. In this pilot study we tested the cytokine pattern of EBC of lung transplant patients with and without clinical evidence of bronchiolitis obliterans syndrome (BOS).     

Investigation of the sorption properties and pharmaceutical application of alpha1-acid glycoprotein by liquid chromatography

The separation and quantitation of the enantiomers and also the determination of the enantiomeric purity are all current and indispensable tasks for the pharmaceutical analysis. The aim of this work was to study the sorption properties of the alpha 1-acid glycoprotein (AGP) based stationary phase, which may have crucial importance for the enantioselectivity. New binding data are presented for the mechanism of the chromatographic separation, which has not clarified in the literature yet. On the basis of these new findings the composition of the mobile phase for a given analytical separation can be designed, including the preparative separation, as well. Binding data for dioxane, known as a solvent with low dielectric constant, are determined at first time. It was found that the sorption of both acetonitrile and dioxane is pH-dependent: as at pH 7.2 the binding can be characterized by a saturation curve, while at pH 4.0 by a twostep, monotone curve. The pH-dependence of the adsorption has been explained by conformational changes of the selector, which were confirmed by CD-spectroscopic and fluorescence quenching study of the native AGP. In accordance with the binding study by increasing the acetonitrile percentage at pH 4.0 a tipical alpha-helical peak was observed in the CD-spectrum. Opposite that at pH 7.2 the increase in the acetonitrile content does not result in any changes in the spectra. Effective dynamic quenching constants of AGP have been determined at given acetonitrile concentrations using 2,2,2-trichloroethanol as fluorescence quencher. In agreement with the results of the CD measurements at pH 4.0 it was found that the degree of quenching enhanced by increasing the amount of the acetonitrile, that can be explained by enhanced exposure of the buried tryptophan residues. Taking these results into account, new optimized and validated HPLC methods have been developed for compendial control in testing the enantiomeric purity of an acidic (ibuprophen), a basic (propranolol) and a neutral (norgestrel) drug molecule.     

Oral symptoms of immunologic disorders. Part I. Systemic autoimmune diseases

Polysystemic autoimmune diseases often cause orofacial and stomatognathic symptoms. Inflammation of the temporomandibular joint only rarely and slightly reduces the range of mouth opening (rheumatoid arthritis), which is much more restricted in systemic sclerosis due to fibrosis of perioral soft tissues. Weakness of masticatory and pharyngeal muscles in idiopathic inflammatory myopathies results in dysphagia and dystonia. Ulcerations, petechiae, teleangiectasia, and lichenoid lesions are the characteristic symptoms of oral mucosal involvement, but drugs used in systemic treatment can also cause very similar side effects. Salivary gland hypofunction (Sj?gren's syndrome) is common, and in addition to the subjective complaints, leads to objective pathologic alterations such as oral mycotic infections, purulent sialadenitis, and increased caries prevalence. The side effects of steroid administration should be taken into account also during dental treatments. Regular dental follow-up and treatment is a basic part of the complex care of these patients in order to diagnose and cure oral abnormalities and salivary gland hypofunction in time. Impairment of hand functions (rheumatoid arthritis, scleroderma) reduces the oral hygienic activity and therefore special devices, local antiseptics and local fluoride preparations are necessary.     

Clinical role of flow velocity of left atrial auricle for prediction of short and long term success of cardioversion in patients with non-valvular atrial fibrillation

INTRODUCTION: Echocardiographic parameters for predicting cardioversion (CV) outcome and long-term sinus rhythm (SR) maintenance in patients with nonvalvular atrial fibrillation (AF) are not accurately defined. AIMS: The authors aim was to evaluate the role of left atrial appendage (LAA) flow velocity detected by transesophageal echocardiography before CV for prediction of short and long-term (1 year) outcome of CV in patients with nonvalvular AF. METHODS: One hundred and nine patients (66 males, mean age: 57 +/- 13 years) with nonvalvular AF lasting more than 48 hours but less than 1-year duration underwent transthoracic and transesophageal echocardiography before either electrical or pharmacological CV attempt. RESULTS: Cardioversion was successful in restoring SR rhythm in 83 (76%) and unsuccessful in patients 26 (24%). Mean LAA peak emptying flow was higher in patients with successful than in those with unsuccessful CV (36.7 +/- 14.7 vs 26.3 +/- 9.2 cm/sec; p < 0.01). At multivariate analysis the left LAA emptying velocity > 32 cm/sec was the only independent predictor of CV success. Seventy-four out of the 83 patients with successful CV had a complete follow-up of 1 year. At the end of the 1-year follow-up, 40 of the 74 (54%) patients who underwent successful CV preserved the SR. Mean LAA peak emptying velocity was higher in patients remaining in SR for 1 year than in those with AF relapse (40.3 +/- 15.6 vs 32.2 +/- 12.2 cm/sec cm/sec; p < 0.001). On multivariate analysis, only the mean LAA peak emptying velocity > 39 cm/sec and the use of preventive antiarrhythmic drug treatment predicted the continuous preservation of SR during 1 year. CONCLUSION: In patients with nonvalvular AF, measurement of precardioversion LAA flow velocity profile by transesophageal echo cardiography provides valuable information for prediction of both short and long-term success of CV.     

Short-term hypobaric hypoxia enhances visual contrast sensitivity

The effect of hypoxia on early visual functions remains a controversial area of research. To explore this question, we measured static and dynamic visual contrast sensitivity in 14 healthy volunteers at a simulated altitude of 5500 m. In comparison with the baseline condition (mean arterial oxygen saturation: 98.4%), contrast sensitivity significantly increased after 5, 10 and 15 min of hypoxic exposure (saturation: 82.9%, 77.0%, 74.3%, respectively). After 10 min, this enhancement was markedly pronounced under dynamic conditions. Returning to the baseline altitude (saturation: 97.7%), contrast sensitivity recovered, mostly at the lower spatial frequencies. There was a significant negative relationship between arterial oxygen saturation and contrast sensitivity values at low and medium spatial frequencies (0.5-4.8 c/deg). These results suggest that early visual processing may be enhanced during short-term hypoxic challenge.     

Catecholamine levels in peripheral blood lymphocytes from multiple sclerosis patients

Circumstantial evidence suggests the involvement of sympathoadrenergic mechanisms in the progress of multiple sclerosis (MS).We studied peripheral blood lymphocytes from MS patients. The levels of dopamine (DA), norepinephrine (NE), epinephrine (E) and their metabolites in extracts of lymphocytes from 58 MS patients and 19 healthy controls were measured by using capillary electrophoresis. The MS patients were divided into clinical subgroups: a laboratory-supported definitive (first-attack) MS group, and a relapsing-remitting (RR) group in remission.The peripheral blood lymphocyte level of epinephrine was significantly higher in the first-attack MS patients (p=0.028) than in the controls. However, the norepinephrine levels were significantly (p=0.027) lower in the RR patients in remission. The catecholamines are known to be able to affect the lymphocyte activity, both by stimulation and by immunosuppression. Our results suggest that the catecholamines are important regulators of lymphocyte activation in MS, and of potential importance as concerns new diagnostic and therapeutic methods.     

Pharmacogenetics of inflammatory bowel disease

There are interindividual variations with regard to efficacy and toxicity of many commonly employed drugs. Major causes of interindividual differences of drug effects include genetic variations of drug-metabolizing enzymes, transporters and targets. Pharmacogenetics studies the genetic background of the interindividual variations of drug response. By means of preliminary genetic screening personalized treatment can be achieved, drugs with low efficacy and many side-effects can be avoided. The pharmacogenetically best studied medications of inflammatory bowel disease are azathioprine/6-mercaptopurine. It is obvious that there is a genetic background of the efficacy and toxicity of corticosteroids, 5-ASA drugs, infliximab and other immunosuppressors as well, but further studies now require to confirm the functional significance of it. Therefore, at present, the application and clinical usefulness of pharmacogenetics in the management of inflammatory bowel disease is limited. The aims of future investigations are understanding of the mechanism of drug action, identification of new drug targets and acquainting with genetic factors that determine drug response.