Clinicopathological and prognostic characterization of oral lichenoid disease and its main subtypes: A series of 384 cases.

BACKGROUND: To clinicopathologically characterize the diagnosis of oral lichenoid disease (OLD) and its main subtypes: oral lichen planus (OLP) and oral lichenoid lesion (OLL), in order to correctly asses their prognosis. MATERIAL AND METHODS: Ambispective cohort study of 384 patients with diagnosis of OLD, based on pre-established clinical and histopathological criteria. We have analysed 272 (70.8%) women and 112 (29.2%), whose mean age was 57.1+/-11.8 years (range 21-90); minimum follow-up time was 36 months. A specific protocol was designed for this study, where we gathered the data of each patient, including malignant transformation. RESULTS: OLP was diagnosed in 229 cases (77.9%) and OLL in 85 (22.1%). Tobacco consumption was found in 20.3% of the patients and alcohol intake in 41.1%. Liver pathology was present in 10.7% of the cases, thyroid pathology in 11.5%, arterial hypertension in 15.6%, diabetes mellitus in 7.6%, psycho-emotional disorders in 33.3%, skin involvement in 12% and genital involvement in 4.9%. Ten patients (2.6%) developed an oral squamous cell carcinoma, 5 (1.7%) with OLP and 5 (5.9%) with OLL. CONCLUSIONS: OLD is a potentially malignant disorder of the oral mucosa which has to be correctly diagnosed as either OLP or OLL, since the risk of malignancy of these subtypes is significantly different.

High-Resolution Melting Assay for Genotyping Variants of the CYP2C19 Enzyme and Predicting Voriconazole Effectiveness.

Voriconazole is a triazole antifungal agent recommended as primary treatment for invasive aspergillosis, as well as some other mold infections. However, it presents some pharmacokinetic singularities that lead to a great variability intra- and interindividually, nonlinear pharmacokinetics, and a narrow therapeutic range. Most experts have recommended tracing the levels of voriconazole in patients when receiving treatment. This azole is metabolized through the hepatic enzyme complex cytochrome P450 (CYPP450), with the isoenzyme CYP2C19 being principally involved. Allelic variations (polymorphisms) of the gene that encodes this enzyme are known to contribute to variability in voriconazole exposure. Three different allelic variants, CYP2C19*17, CYP2C19*2, and CYP2C19*3, could explain most of the phenotypes related to the voriconazole metabolism and some of its pharmacokinetic singularities. We designed a rapid molecular method based on high-resolution melting to characterize these polymorphisms in a total of 142 samples, avoiding sequencing. Three PCRs were designed with similar cycling conditions to run simultaneously. The results showed that our method represents a fast, accurate, and inexpensive means to study these variants related to voriconazole metabolism. In clinical practice, this could offer a useful tool to individually optimize therapy and reduce expenses in patients with fungal infections.

Oral lichenoid lesions associated with amalgam restorations: a prospective pilot study addressing the adult population of the Basque Country.

UNLABELLED: Oral lichenoid lesions (OLLs) are linked to a heterogeneous group of pathologies involving the oral mucosa that cannot be distinguished from the oral lichen planus excepting the fact that direct causal factors such as silver amalgam restorations (SARs) can be allocated to them. PURPOSE: To analyze the prevalence of mucosal lesions associated with SAR in a group of SAR carrying patients in the Basque Country. STUDY DESIGN: A clinical prospective study was carried out on 100 adult patients over 30 years of age at the UPV/EHU Clinical Odontology Service whose rear teeth had at least one SAR. Patients were identified and mucosal lesions and amalgam restorations were characterized. Patch tests were performed on patients with lesions and amalgams were replaced with composite material. A statistical and comparative analysis was performed with the resulting data. RESULTS: OLLs were found in 7 patients whose predominant lesion was bilateral, asymmetrical and asymptomatic white papule-macule. Lesions were related to old and corroded SARs. Patch testing was positive in two cases. SAR substitution produced an improvement in 5 cases. CONCLUSIONS: The presence of lichenoid lesions associated with SARs is infrequent in our environment and is preferentially related to old and corroded restorations.

Pathway towards an ideal and sustainable framework agreement for the public procurement of vaccines in Spain: a multi-criteria decision analysis.

Objective: To advance the development of an ideal and sustainable framework agreement for the public procurement of vaccines in Spain, and to agree on the desirable award criteria and their relative weight. Methods: A multidisciplinary committee of seven health-care professionals and managers developed a partial multi-criteria decision analysis to determine the award criteria that should be considered and their specific weights for the public procurement of routine vaccines and seasonal influenza vaccines, considering their legal viability. A re-test of the results was carried out. The current situation was analyzed through 118 tender specifications and compared to the ideal framework. Results: Price is the prevailing award criterion for the public procurement of both routine (weighting of 60% versus 40% for all other criteria) and influenza (36% versus 64%) vaccines. Ideally, 22 criteria should be considered for routine vaccines, grouped and weighted into five domains: efficacy (weighting of 29%), economic aspects (27%), vaccine characteristics (22%), presentation form and packaging (13%), and others (9%). Per criteria set, price was the most important criterion (22%), followed by effectiveness (9%), and composition/formulation (7%). Regarding influenza vaccines, 20 criteria were selected, grouped, and weighted: efficacy (29%), economic aspects (25%), vaccine characteristics (20%), presentation form and packaging (16%), and others (11%). Per criteria set, price was also the most relevant criterion (19%), followed by composition/formulation (8%), and effectiveness (8%). Conclusions: Contrary to the current approach, technical award criteria should prevail over economic criteria in an ideal and sustainable framework agreement for the public procurement of vaccines.

[Lafora and neuropathology]. / Lafora y la neuropatología.

This article wants to be a memory to the figure and neuro-pathologic work of D. Gonzalo Rodríguez-Lafora. The tediousness of its neurological work allows to divide it in its slopes neurophatologic, neurophysiologic, clinic and therapy. Also, it embraces other topics outside of the field of the neurology, centered fundamentally in the psychiatry. It is without a doubt the facet neuro-histopathologic the one that provides him bigger national and international prestige and it contributes to deepen in the histopathology of the senility, picking up in a definitive way in their work critical valuation of the discoveries histopathological in the senility (1952) their thought in this respect. Mention separated deserves its more important discovery: The inclusions amylaceous in cells ganglionars, in a certain type of epilepsy myoclonic that today takes its name. Other entities like the illness of Wernicke, the hemorrhages hipofisarias, the Parkinson (for scarce months he is not early to Levy in an important discovery), or the alterations of the malaria in the cerebral fabric plows object of their attention, of the work of Lafora highlights its anatomo-pathologics works next to figures as Kraepelin, Alzheimer, Vogt, Openheim or Brodmann. Professor Lafora's figure is known internationally as neuropathologist, recognizing its contribution, collection in the world literature, to the study of the myoclonic epilepsy: 'Lafora disease. A form of progressive myoclonus epilepsy.

[Ischemic infarct, mitral valve prolapse and protein S deficiency]. / Infarto isquémico, prolapso de válvula mitral y déficit de proteína S.

Ischaemic stroke in young people, that is in those under 45 years of age, forms a distinct entity. Whereas in the case of older patients the main cause is arteriosclerosis, in the younger group a broad spectrum of etiologies can be found. It is for this reason that in these latter cases we must carry out a diagnostic study that is not only more exhaustive but also additionally is aimed at seeking out specific pathologies as for instance a possible association with vasculitis, infectious diseases, hematological abnormalities or unclear cardiopathology. Given the therapeutic transcendency that findings might have, in order to avoid new bouts in patients at the most productive moments in their lives, we believe it to be of great interest to carefully study these patients as exhaustively as need be. In the present work we present the case of a young patient with ischaemic infarct in the region of both upper cerebella which started out with a clinical picture of ataxia and dysarthria with benign course and total recovery. Possible etiologies are discussed in the light of findings made during complementary tests, as well as the unusual location of the lesions.

[Untreatable hiccup as un unusual sign in a rostral occlusion syndrome of the basilar artery]. / Hipo intratable como manifestación inusual de un síndrome de oclusión rostral de la arteria basilar.

Hiccoughs (singultus) is a habitual physiological phenomenon, the persistence of which might indicate neurological and extraneurological multiple lesions. Its activation involves starting up numerous central and peripheral mechanisms which have yet to be clearly determined. Hiccoughs results from an intermittent myoclonus of the diaphragm, reflex in origin, with unknown authentic cause or physiological significance. It has been suggested that, more than just an abnormal reflex, it could be a type of myoclonus brought on by repeated activity of the 'solitary inspiratory nucleus', by releasing control of the inhibiting-activating upper nervous system activity. We present the case of a patient with uncontrollable hiccoughs lasting over six years as a result of paramedial bilateral thalamic ischaemia (rostral occlusion syndrome of the basilar artery type 1) of cardioembolic origin (auricular fibrillation) secondary to hyperthyroidism.

[Segmental arteriographic anomalies in migranous cerebral infarct]. / Anomalías arteriográficas segmentarias en el infarto cerebral migrañoso.

A migranous cerebral infarct (ICM) has the appearance of an ischaemic cerebral lesion which occurs during a migraine crisis and is shown by neuroimaging techniques to be in the corresponding vascular area. Four young patients are described. They fulfilled the clinical and neuroimaging criteria for compatibility with ICM and the protocol for the aetiological study of stroke was normal. Angiography ruled out other causes of ischaemia (dissection, fibromuscular dysplasia, etc.) and showed segmental images of 'vasculitis appearance' similar to these described in Call's syndrome, in 'benign intracranial angiopathy' and in other intracranial vasculopathies or criteria of 'reversible segmental cerebral vasoconstriction'. The pathogenic significance, as with migraine, is still unknown.

Borrelia burgdorferi gene expression in vivo and spirochete pathogenicity.

Borrelia burgdorferi spirochetes that do not cause arthritis or carditis were developed and used to investigate Lyme disease pathogenesis. A clonal isolate of B. burgdorferi N40 (cN40), which induces disease in C3H/HeN (C3H) mice, was repeatedly passaged in vitro to generate nonpathogenic spirochetes. The passage 75 isolate (N40-75) was infectious for C3H mice but did not cause arthritis or carditis, and spirochetes were at low levels or absent in the joints or hearts, respectively. N40-75 could, however, cause disease in severe combined immunodeficient (SCID) mice, suggesting that the response in immunocompetent mice prevented effective spirochete dissemination and the subsequent development of arthritis and carditis. Administration of immune sera at 4 days after spirochete challenge aborted N40-75, but not cN40, infection in SCID mice. A B. burgdorferi genomic expression library was differentially probed with sera from cN40- and N40-75-infected mice, to identify genes that may not be effectively expressed by N40-75 in vivo. N40-75 was defective in the up-regulation of several genes that are preferentially expressed during mammalian infection, including dbpAB, bba64, and genes that map to the cp32 family of plasmids. These data suggest that adaptation and gene expression may be required for B. burgdorferi to effectively colonize the host, evade humoral responses, and cause disease.