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Biomedical subjects

M Carrozzo

Publications and source records attributed to M Carrozzo.

At least 19 recordsLinked to original sources

Sequential immunohistochemical p53 expression in biopsies of oral lichen planus undergoing malignant evolution.

Transformation in squamous cell carcinoma (SCC) may occur in a small percentage of patients affected by oral lichen planus (OLP), but the pathogenesis remains to be elucidated. Overexpression of p53 protein was investigated immunohistochemically in 28 cases of OLP, followed up by sequential biopsies for up to 96 months. In 15 cases (Group 1), no dysplastic changes or neoplastic transformation occurred during the follow-up period; in 7 cases, OLP and SCC were synchronously observed (Group 2), whereas in another 6 cases (Group 3) SCC developed several months or years after diagnosis of OLP. The percentage of p53-positive epithelial cells at first diagnosis was significantly higher in the cases of Groups 2 and 3 than in those of Group 1. In contrast, evaluation of growth fraction by MIB-1 monoclonal antibody did not show any statistical differences among the three groups. Although no conclusions can be drawn about the molecular pathway leading to neoplastic transformation of OLP, or about the role of p53, the results indicate that immunohistochemical evaluation of p53 expression may be a practical tool to select cases of OLP with a high risk of neoplastic transformation.

Aged↗

Increased frequency of HLA-DR6 allele in Italian patients with hepatitis C virus-associated oral lichen planus.

BACKGROUND: Recent controlled studies have confirmed that hepatitis C virus (HCV) is the main correlate of liver disease in patients with lichen planus (LP), mainly in southern Europe and Japan. However, a low prevalence of HCV infection has been found in LP patients in England and northern France, and significant differences in serum HCV RNA levels or HCV genotypes have not been found between LP patients and controls. Thus host rather than viral factors may be prevalent in the pathogenesis of HCV-related LP. The HLA-DR allele may influence both the outcome of HCV infection and the appearance of symptoms outside the liver. OBJECTIVES: To assess whether major histocompatibility complex class II alleles play a part in the development of HCV-related LP. METHODS: Intermediate-resolution DRB typing by hybridization with oligonucleotide probes was performed in 44 consecutive Italian oral LP (OLP) patients with HCV infection (anti-HCV and HCV RNA positive), in an age, sex and clinically comparable disease control group of 60 Italian OLP patients without HCV infection (anti-HCV and HCV RNA negative), and in 145 healthy unrelated Italian bone marrow donors without evidence of liver disease or history of LP and with negative tests for HCV. RESULTS: Patients with exclusive OLP and HCV infection possessed the HLA-DR6 allele more frequently than patients with exclusive OLP but without HCV infection (52% vs. 18%, respectively; Pc (Pcorrected) = 0.028, relative risk = 4.93). We did not find any relationship between mucocutaneous LP, HCV infection and HLA-DR alleles. CONCLUSIONS: HCV-related OLP therefore appears to be a distinctive subset particularly associated with the HLA class II allele HLA-DR6. This could partially explain the peculiar geographical heterogeneity of the association between HCV and LP.

Adult↗

Hepatitis C virus-associated oral lichen planus: no influence from hepatitis G virus co-infection.

There is a variable geographic distribution in the prevalence of hepatitis C virus (HCV)-related oral lichen planus (OLP), which appears unrelated to either HCV genotype or HCV epidemiology. The present study investigated whether hepatitis G virus (HGV) co-infection may be a feature of patients with HCV-related OLP, which might explain these phenomena. HGV co-infection was detected in 6 of 39 Italian patients with HCV-related OLP, but the presence of HGV did not influence the clinical presentation of OLP. It is concluded that HGV co-infection is unlikely to influence the clinical detection of HCV-related OLP.

Adult↗

Previous tuberculosis, hepatitis C virus and lichen planus. A report of 10 cases, a causal or casual link?

We report 10 cases of lichen planus (LP) and chronic liver disease linked to HCV. The mean age was 63.4 +/- 5.1 years (range 51-73), five were female; six patients had an established cirrhosis of the liver, as shown by either a liver biopsy or the ultrasonographic and biohumoral evidence. The remaining four patients had chronic hepatitis. Histological examination confirmed the presence of LP: the localization of the dermatosis was restricted to the skin in four patients, to the mucous membranes in five (4 atrophic erosive and one erosive) while the remaining had mucous-cutaneous localization. A type II cryoglobulinemia was demonstrated in two and a type III in one of the patients, while no one had otherwise circulating autoantibodies (anti-nuclear, anti-smooth muscle, anti-liver kidney microsomal type 1 and anti-mitochondrial antigens) such as other etiological factors of liver disease. In six of the patients the history was positive for previous Mycobacterium tuberculosis infection. In clinical practice the patients with chronic liver disease and HCV infection can also suffer from severe extrahepatic manifestations, including lichen planus.

Aged↗

Viewer-centered and body-centered frames of reference in direct visuomotor transformations.

It has been hypothesized that the end-point position of reaching may be specified in an egocentric frame of reference. In most previous studies, however, reaching was toward a memorized target, rather than an actual target. Thus, the role played by sensorimotor transformation could not be disassociated from the role played by storage in short-term memory. In the present study the direct process of sensorimotor transformation was investigated in reaching toward continuously visible targets that need not be stored in memory. A virtual reality system was used to present visual targets in different three-dimensional (3D) locations in two different tasks, one with visual feedback of the hand and arm position (Seen Hand) and the other without such feedback (Unseen Hand). In the Seen Hand task, the axes of maximum variability and of maximum contraction converge toward the mid-point between the eyes. In the Unseen Hand task only the maximum contraction correlates with the sight-line and the axes of maximum variability are not viewer-centered but rotate anti-clockwise around the body and the effector arm during the move from the right to the left workspace. The bulk of findings from these and previous experiments support the hypothesis of a two-stage process, with a gradual transformation from viewer-centered to body-centered and arm-centered coordinates. Retinal, extra-retinal and arm-related signals appear to be progressively combined in superior and inferior parietal areas, giving rise to egocentric representations of the end-point position of reaching.

Adult↗

Update on mucous membrane pemphigoid: a heterogeneous immune-mediated subepithelial blistering entity.

Most oral involvement in the skin diseases (dermatoses) is related to mucous membrane pemphigoid or lichen planus. Mucous membrane pemphigoid was the subject of a European Symposium held in Turin, Italy, in June 1997. This review is based on that symposium. Mucous membrane pemphigoid is a subepithelial vesiculobullous disorder mainly of late middle age; it has a slight predilection for women. Whereas mucous membrane pemphigoid was formerly considered a single entity, it is now quite evident that a number of subepithelial vesiculobullous disorders may produce similar clinical pictures and also that a range of variants of mucous membrane pemphigoid exists, with antibodies directed against various hemidesmosomal components or components of the epithelial basement membrane. The term immune-mediated subepithelial blistering diseases has therefore been used. Diagnosis and management of immune-mediated subepithelial blistering diseases on clinical grounds alone are impossible; a full history, general and oral examinations, and biopsy with immunostaining are now invariably required, sometimes supplemented with other investigations. Most patients with mucous membrane pemphigoid affecting the mouth manifest desquamative gingivitis, a fairly common complaint typically seen in women who are middle-aged or older. Oral vesicles and erosions may also occur, and there can be a positive Nikolsky sign. Some patients have lesions of other stratified squamous epithelia, presenting as conjunctival, nasal, oesophageal, laryngeal, vulval, penile, or anal involvement. Apart from improving oral hygiene, immunomodulatory-in particular, immunosuppressive-therapy is typically required to control oral lesions in mucous membrane pemphigoid. No single treatment regimen reliably controls all these disorders.

Eye Diseases↗

Oral lichen planus in patients infected or noninfected with hepatitis C virus: the role of autoimmunity.

Serum proteins, serum immunoglobulins, anti-nuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), anti-mitochondrial antibodies (AMA), anti-liver-kidney antibodies (LKM), anti-parietal-cell gastric antibodies (APCA), anti-epithelial antibodies and concomitant autoimmune disease were studied in 27 OLP-HCV+ve subjects and in a comparable group of 23 who were OLP-HCV-ve. In addition, all the patients with chronic liver disease who were sero-positive for ANA, AMA or LKM were scored using the new aggregate scoring system to detect those with the accepted criteria for the diagnosis of autoimmune hepatitis (AIH). Hypergammaglobulinemia was more frequent in OLP-HCV+ve than in OLP-HCV-ve (P = 0.008) subjects. Serum IgG and IgM levels were higher in HCV+ve than in HCV-ve (respectively, P = 0.017 and P = 0.018) individuals. However, there was no difference in the frequency of any autoantibody between OLP-HCV+ve and OLP-HCV-ve patients. Overall, immunologically-related abnormalities were found in 17(63%) OLP-HCV+ve and 11(48%) OLP-HCV-ve (P = 0.43) patients. Three OLP-HCV-ve and no OLP-HCV+ve patients had score criteria of probable AIH. The present and our previous data suggest that OLP patients with HCV infection neither had evidence of autoimmune liver damage nor had abnormal humoral immune-responses, with the exception of higher than control levels of serum immunoglobulins. Cryoglobulins may be responsible.

Adult↗

Topical corticosteroids in association with miconazole and chlorhexidine in the long-term management of atrophic-erosive oral lichen planus: a placebo-controlled and comparative study between clobetasol and fluocinonide.

OBJECTIVE: To evaluate the efficacy of a combination of topical corticosteroids with topical antimycotic drugs in the therapy of atrophic-erosive forms of oral lichen planus (OLP). PATIENTS AND METHODS: The study population consisted of 60 patients with OLP subdivided into three groups matched for sex and age. The first group (25 patients) and the second group (24 patients) received respectively 0.05% clobetasol propionate ointment or 0.05% fluocinonide ointment in an adhesive medium (4% hydroxyethyl cellulose gel) plus in each case antimycotic treatment consisting of miconazole gel and 0.12% chlorhexidine mouthwashes. The third group (11 patients), placebo group, received only hydroxyethyl cellulose gel and antimycotic treatment as above. All the treatment regimens were carried out for 6 months. Each patient was examined every 2 months during the 6-month period of active treatment and for a further 6 months of follow-up. Objective and subjective clinical progress was scored and compared between the three groups. Plasma cortisol levels were monitored in half the patients using the topical corticosteroids. RESULTS: All patients treated with clobetasol and 90% of the patients treated with fluocinonide witnessed some improvement, whereas in the placebo group only 20% of patients improved (P < 0.0001 and P = 0.00029, respectively. However, when considering complete responses, only clobetasol gave significantly better results than placebo. Clobetasol resolved 75% of the lesions whereas fluocinonide was effective in 25% of cases and placebo in none. Clobetasol achieved better results statistically than did fluocinonide (P = 0.00442) and placebo (P = 0.00049) whereas there was no statistical difference among fluocinonide and placebo (P = 0.140). Similar results were obtained for symptoms. Both drugs were shown to be effective in the treatment of erosive lesions, but clobetasol was considerably more efficacious than fluocinonide in the atrophic areas (75% vs 25% of total response, respectively) (P = 0.00442). None of the treated patients contracted oropharyngeal candidiasis. After 6 months of follow-up, 65% of the clobetasol-treated group and 55% of the fluocinonide group were stable. Estimation of plasma cortisol levels showed no significant systemic adverse effects of clobetasol or fluocinonide. CONCLUSIONS: Our results suggest that a very potent topical corticosteroid such as clobetasol may control OLP in most cases, with no significant adrenal suppression or adverse effects. Moreover, a concomitant antimycotic treatment with miconazole gel and chlorhexidine mouthwashes is a useful and safe prophylaxis against oropharyngeal candidiasis.

Administration, Topical↗

The management of oral lichen planus.

OBJECTIVE: To review the current literature regarding the medical treatment of oral lichen planus (OLP). DATA SOURCES: PubMed on-line Medline data searches were carried out for the years 1966-1998 to identify reports on therapy of OLP. METHODS OF STUDY SELECTION: Single case reports or open trials were included if they covered new therapeutic approaches or suggested significant modifications of known treatment modalities. Review papers were limited to those dealing with the topic. DATA EXTRACTION AND SYNTHESIS: Every paper was critically examined. Because of the great heterogeneity of the response criteria, many data could not be directly compared. Stronger weight was given to therapies that have proven to be effective under placebo-controlled research protocols. Attention was also drawn to potential and effective adverse effects of every drug used. CONCLUSIONS: Among the various medications advocated for the treatment of OLP, several lack conclusive findings from adequately controlled trials. Mainly high-potency topical corticosteroids in an adhesive medium appear at present the safest and most efficacious. Adjuvant agents as antimycotics may be useful in topical steroid treatment. Systemic corticosteroids may be occasionally indicated for severe recalcitrant erosive OLP or for diffuse mucocutaneous involvement. Topical cyclosporine should be considered in steroid-unresponsive cases considering that its efficacy in OLP could be related to a systemic effect and its high cost. Classical PUVA therapy seems to have too many side effects; topical application of psoralen is promising but still experimental. Topically and systemically delivered retinoids combined with topical corticosteroids could improve the efficacy of these agents whereas complete remission is difficult to achieve with retinoids alone and they frequently cause adverse effects. Finally, there are only few data concerning the long-term effect of the medical treatments upon the course of OLP and we do not know if therapy influences the malignant evolution of OLP.

Adrenal Cortex Hormones↗

[Erythema multiforme. A heterogeneous pathologic phenotype].

The term Erythema Multiforme (EM) include actually a wide range of clinical expressions, from exclusive oral erosions (Oral EM) to mucocutaneous lesions (EM Minor), sometimes with severe involvement of multiple mucosal membrane (EM major, Stevens-Johnson syndrome [SJS]) or with involvement of a large area of the total body surface (toxic epidermal necrolysis [TEN]). However, this terminology is not worldwide accepted and often the various clinical categories show some overlapping features. Among the great number of suspected etiological factors, herpes simplex virus is involved in many cases of EM minor whereas SJS and TEN are caused in 80% of cases by systemic drugs, mainly by anticonvulsivants, sulfonamides, nonsteroidal anti-inflammatory drugs and antibiotics. Several oral EM seem idiopathic, but data on this topic are very few. There is no specific or consistent microscopic and immunopathologic pattern of EM and the diagnosis should be done by excluding other similar diseases. The treatment include the use of antivirals for EM minor, mainly if recurrent, and of immunosuppressants (especially systemic corticosteroids) for SJS. TEN patients require adequate supportive care and often they have to be treated in emergency departments. Finally, patients with exclusive oral lesions may be treated with both topical and systemical corticosteroids.

Adolescent↗

Virtual reality: a tutorial.

Virtual reality (VR) technology is complex and relies on multidisciplinary knowledge. VR applications are attracting an increasing interest among neuroscientists, in particular in the study of the human brain. Here we present a brief tutorial in which we address aspects of VR methodology that are most relevant to neurophysiology applications. After a brief survey of possible applications to neurophysiology, we discuss the following issues in VR: display technology, visual stimulus presentation techniques, visual spatial resolution and accuracy, devices for real-time interaction with the virtual environment and force-feedback.

Humans↗

Altered expression of alpha 6 integrin subunit in oral squamous cell carcinoma and oral potentially malignant lesions.

The expression and distribution of integrin chains alpha 2, alpha 3, alpha 5, alpha 6, beta 1, beta 4, collagen type IV, laminin 1 and laminin 5 in oral squamous cell carcinoma (SCC) and oral keratoses with and without dysplasia (OL) have been studied by immunochemistry and western blotting. Focal interruptions of basement membrane protein staining were detected in SCC indicating a loss of continuity, whereas tumour nests were apparently completely surrounded by laminin 1, type IV collagen and laminin 5; the loss of basement membrane components in OL was found in only one specimen showing severe dysplasia. The localisation of integrins showed altered suprabasal and pericellular expression of the alpha 6 chain in all but one SCC, as well as in many OL samples, whereas the beta 4 subunit showed only a faint pericellular redistribution in SCC. In OL, beta 4 was often seen in a normal basally polarised distribution. Western blotting analysis confirmed that alpha 6 protein levels were abnormally high in cancerous lesions, whereas quantitative recovery of the beta 4 subunit in SCC was only minimal, suggesting a dissociation in the synthetic ratios of the two chains of the alpha 6 beta 4 heterodimer in SCC. Because alterations in the polarised expression of integrin alpha 6 beta 4 have been seen during epithelial tumour progression and wound healing, we suggest that the lack of restricted basal polarisation of alpha 6 could be an early but non-specific marker of oral malignancy, indicating that the generation of abnormal signals from the extracellular matrix may be involved.

Antigens, CD↗

[An increase in gingival volume induced by drugs (phenytoin, cyclosporine and calcium antagonists). A review of the literature].

The aim of this review is to evaluate the side effects of some drug therapies on the gingival tissue in certain susceptible individuals. Phenytoin, cyclosporine-A and a variety of calcium channel blockers have been shown to produce gingival overgrowth. In this paper the pharmacodynamics and pharmacokinetics of these drugs, the pathogenesis, the clinical aspect of the enlargement and its treatment are examined. Several of the reviewed theories on pathogenesis are well documented in the literature, while others are controversial and less described. The old term gingival hyperplasia is not exact because histologically an increase in the number of fibroblasts has not been demonstrated, but an increase has been found out in the amount of collagen fibers and noncollagenous proteins in the connective tissue. The clinical findings have the same characteristics both in location and growth pattern while prevention is primarily directed at the removal of local irritant factors. The prevalence and severity of gingival enlargement increase in heart transplant patients who are often medicated with cyclosporin and channel blockers.

Anticonvulsants↗

Systemic corticosteroid therapy of oral vesiculoerosive diseases (OVED). An open trial.

BACKGROUND: We report the preliminary findings from our open study on how to optimize the doses and the response times to systemic corticosteroid therapy for three forms of oral vesiculoerosive diseases (OVED). METHODS: All twenty-one patients enrolled in the study were affected with OVED (10 OLP, 6 MMP, 5 EM) and received different doses of prednisone in relation to the type of disease and its severity. Daily mouthwashes with 0.12% chlorhexidine and application of miconazole gel were added to the therapy; its response time to treatment varied individually, the doses were reduced only after 75% of lesions had cleared. RESULTS: The average response time to treatment was 28 days. Clinical assessment showed that 95% of the patients had improved, whereas 71% had complete remission of oral signs and 48% experienced side effects. The degree of clinical resolution was: 70% complete remission after 26 days of therapy in patients with OLP, 33% complete remission after 38 days in patients with MMP, and 100% complete remission after ten days in patients with EM. CONCLUSIONS: Although a preliminary study, initial results showed different types and times of response to systemic corticosteroid treatment for the three diseases. Our findings strongly suggest that a unified therapeutic protocol for different OVED is not advisable, nor can systemic treatment be considered the first therapeutic approach.

Adolescent↗

Visuomotor transformations for reaching to memorized targets: a PET study.

Positron emission tomography (PET) was used to identify cortical and subcortical regions involved in the control of reaching to visual targets. Regional cerebral blood flow (rCBF) was measured in eight healthy subjects using H2(15)O PET during the performance of three different tasks. All tasks required central fixation while a 400-ms target was flashed every 5 s at a random location around a virtual circle centered on the fixation target. Additional instructions differed according to the task: (i) visual detection of the target without overt responses; (ii) immediate pointing to the most recent target in the sequence, and (iii) pointing to the previous target in the sequence. By design, the two motor tasks differed in the cognitive processing required. In each trial of immediate pointing, the spatial location of only the most recent target needed to be processed. In each trial of pointing to the previous, instead, while the most recent target was stored in memory for the movement of the next trial, the previous target had to be retrieved from memory to direct the current movement. Limb trajectories were comparable between the two motor tasks in terms of most spatiotemporal parameters examined. Significant rCBF increases were identified using analysis of covariance and t statistics. Compared with visual detection there was activation of primary sensorimotor cortex, ventrolateral precentral gyrus, inferior frontal gyrus in the opercular region, supramarginal gyrus, and middle occipital gyrus, all these sites in the hemisphere (left) contralateral to the moving limb, and cerebellar vermis, during both immediate pointing and pointing to the previous. During immediate pointing there was additional activation of left inferior parietal lobule close to the intraparietal sulcus, and when compared with pointing to the previous, dorsolateral prefrontal cortex bilaterally. During pointing to the previous, instead, there was additional activation of supplementary motor cortex, anterior and midcingulate, and inferior occipital gyrus in the left hemisphere; superior parietal lobule, supramarginal gyrus, and posterior hippocampus in the right hemisphere; lingual gyri and cerebellar hemispheres bilaterally; anterior thalamus; and pulvinar. The activation of two partially distinct cerebral networks in these two motor tasks reflects the different nature of signal processing involved. In particular, the specific activation of intraparietal sulcus and prefrontal cortex in immediate pointing appears characteristic of a network for visuospatial working memory. By contrast, the corticolimbic network engaged in pointing to the previous could mediate spatial attention and the sequence of encoding, recording, and decoding of spatial memories required by a dual task with two competing targets.

Adult↗

An atypical verrucous carcinoma of the tongue arising in a patient with oral lichen planus associated with hepatitis C virus infection.

Recently, a clinical relationship between oral lichen planus (OLP) and hepatitis C virus (HCV) infection has been suggested, but the role of this virus on the course of OLP is unknown. We report an unusual lingual localisation of verrucous carcinoma arising in a patient with histologically confirmed OLP and HCV infection diagnosed with second generation enzyme-linked immunosorbent assay and recombinant immunoblot assay. Serum HCV-RNA detected using nested reverse transcriptase polymerase chain reaction (RT-PCR) confirm HCV replication. No classical risk factors associated with verrucous carcinoma were present.

Aged↗

HCV genotypes in Italian patients with HCV-related oral lichen planus.

Hepatitis C virus (HCV) has high genomic variability and since its discovery, six different "types" and an increasing number of "subtypes" have been reported. HCV genotype may influence viral replication, natural history of disease and response to therapy. Recently, an association between lichen planus (LP) and HCV infection has been suggested, as there is an increased frequency of HCV infection among some groups of patients with LP, in particular from Italy and Japan. These results have not been confirmed by other reports from different geographical areas. Since HCV genotypes have a heterogeneous geographical distribution, we have determined by restriction fragment length polymorphism the genotypes of 39 HCV-seropositive Italian patients with oral LP in order to establish whether the association between LP and HCV infection is influenced by HCV subtype. Of the 33 (84.6%) viraemic patients, 17 (51%) were infected by HCV subtype 1b, 9 (27%) were infected by HCV subtype 2a, 2 by subtype 1a and 1 by subtype 2b. In four cases the gel patterns were uninterpretable. This distribution of HCV genotypes is similar to that reported in recent studies of Italian HCV-seropositive patients of unknown LP status. It is concluded from this small sample that the association of lichen planus with HCV infection and its differential geographic distribution is unlikely to be due to infection by a particular HCV genotype.

Adult↗

[Melanoma of the oral cavity. Review of the literature].

The location of melanoma in the oral cavity is extremely rare: its frequency varies between 0.2 and 8%. Oral melanoma strikes mainly male subjects and is more frequently seen at the level of the hard palate and gingiva. Today the clinicopathological classification of oral melanoma is not yet clearly outlined, and that is why the skin form is often taken as a reference. The acral lentiginous subtype proves to be the most common in this seat. In many cases (up to 50%) the diagnosis of melanoma is made on lesions which have evolved from the pre-existing pigmented lesions: as a consequence, every pigmented lesion of undetermined origin must be biopsied as a routine. The prognosis often proves poor and the surgical approach, combined with the chemotherapeutic one, is the first choice treatment. Lymph node dissection is not routinely practiced.

Antineoplastic Agents↗