Testing for equivalence: an intersection-union permutation solution

The notion of testing for equivalence of two treatments is widely used in clinical trials, pharmaceutical experiments,bioequivalence and quality control. It is essentially approached within the intersection-union (IU) principle. According to this principle the null hypothesis is stated as the set of effects lying outside a suitably established interval and the alternative as the set of effects lying inside that interval. The solutions provided in the literature are mostly based on likelihood techniques, which in turn are rather difficult to handle, except for cases lying within the regular exponential family and the invariance principle. The main goal of present paper is to go beyond most of the limitations of likelihood based methods, i.e. to work in a nonparametric setting within the permutation frame. To obtain practical solutions, a new IU permutation test is presented and discussed. A simple simulation study for evaluating its main properties, and three application examples are also presented.Comment: 21 pages, 2 figure

Humoral immunological parameters in Italian patients with oral lichen planus

Serum humoral immunological parameters were determined in 25 patients with atrophic-erosive forms of oral lichen planus (OLP) (Group 1), in 28 patients with reticular-plaque-like lesions of OLP (Group 2) and in 21 healthy patients without oral lesions (Group 3). Comparing patients affected by atrophic-erosive forms of OLP (Group 1) with normal Controls (Group 3), increased levels of serum IgG approaching the statistical significance were found (Kruskal-Wallis test p = 0.0572). It was also found a significantly higher value of kappa (Kruskal-Wallis test p = 0.0017; Mann-Whitney test with Bonferroni’s correction p < 0.001) and lambda (Kruskal-Wallis test p = 0.0346; Mann-Whitney test with Bonferroni’s correction p = 0.013) light chains in patients with atrophic-erosive OLP (Group 1) as compared with normal controls (Group 3). However these higher levels were probably caused by strong prevalence of chronic liver diseases (40%), in patients with atrophic-erosive variety of OLP. No one of these patients was affected by autoimmune liver disease. No differences were noted between atrophic-erosive OLP (Group 1) and hyperkeratosic OLP (Group 2). This study does not confirm the suggestion that patients with OLP may have a generalized immunologic disorder and it also add some evidences that the role of humoral immunity in the pathogenesis of OLP is probably secondary to the cell-mediated reaction against basal keratinocytes.Les principaux aspects de l’immunologie humorale ont été évalués dans deux groupes de malades porteur d’un lichen plan de la muqueuse buccale, 25 à formes atrophiques-érosives (Groupe 1), 28 à formes en réseaux ou en plaques blanches (Groupe 2), et chez 21 sujets sains. Au terme de cette étude les différences les plus remarquables sont les suivantes: le taux des IgG sériques est nettement plus élevé chez les sujets du Groupe 1 ce qui est presque significatif par rapport au Groupe 3 (p = 0.0577). L’analyse statistique a surtout révélé des différences significatives entre le Groupe 1 et le Groupe 3 (contrôle) en ce qui concerne les taux sériques des chaînes Kappa (Kruskal-Wallis test p = 0.0017; Mann-Whitney test corrigé par Bonferroni p < 0.001 ) et des chaînes Lambda (Kruskal-Wallis test p = 0.0346; Mann-Whitney test corrigé par Bonferroni p = 0.013). Aucune autre différence significative entre les trois groupes n’a été observee. Nous pensons que ces résultats sont probablement dus à la présence d’une hépatopathie chronique non auto-immune qui a été diagnostiquée dans 40% des cas du Groupe 1. Cette étude ne confirme donc pas la thèse selon laquelle les sujets atteints de lichen plan buccal pourraient avoir une défaillance de l’immunité humorale. Elle nous permet de penser que le rôle de cette dernière dans la pathogénèse de la maladie est probablement secondaire à la réaction cellulaire dirigée contre les kératinocytes

Phenotypic analysis of peripheral blood cell immunity in Italian patients with different varieties of oral lichen planus

Quantitative analysis of peripheral blood lymphocytes was carried out in 25 patients with atrophic-erosive type of oral lichen planus (OLP) (Group 1), in 28 patients with reticular-plaque like lesions of OLP (Group 2) and in 21 healthy patients (Group 3) by using flow cytometry. CD4 + subsets decreased significantly in patients with reticular-plaque like varieties when compared with healthy patients (Group 3) (One way analysis of variance p = 0.039; t-test with Bonferroni correction p< 0.05). Moreover, in patients with hyperkeratosic forms of OLP (Group 2) CD8 + cell populations were significantly higher than in controls (Group 3) (Kruskal-Wallis test p = 0.035; Mann-Whitney test with Bonferroni’s correction p< 0.0001) and consequently CD4/CD8 ratio was significantly lower in patients with reticular-plaque like lesions than in controls (Kruskal-Wallis test p = 0.01; Mann-Whitney test with Bonferroni’s correction p = 0.013). No statistical differences between patients of Group 1 (atrophic-erosive OLP) and the other two Groups (hyperkeratosic OLP and healthy controls) were detected. 40% of the patients of Group 1 were affected by chronic hepatopathies, most of which were related to hepatitis C virus (HCV), but the data were not substantially modified after adjustment for the patients with chronic liver disease HCV positive. There is no clear evidence that these results indicate the existence of a different pathogenetic mechanism between erosive-atrophic and hyperkeratosic types of OLP. On the other hand, these results and the previously reported immunohistochemical findings suggest that quantitative alterations of peripheral blood lymphocytes in hyperkeratosic varieties of OLP could represent a shift of CD4 + cells from the vascular to the oral mucosa compartment.Les lymphocytes du sang périphérique ont été évalués par cytométrie de flux dans deux groupes de malades porteurs d’un lichen plan de la muqueuse buccale: 25 à forme atrophique-érosive (Groupe 1), 28 à forme en réseaux ou en plaques blanches (Groupe 2), et chez 21 sujets sains (Groupe 3). Au terme de cette étude les différences les plus remarquables ont été les suivantes: diminution de la fraction CD4 + et une augmentation de la fraction CD8 + dans le Groupe 2 (réseaux et plaques blanches) comparés au Groupe 3 (contrôle), la différence est statistiquement significative (One ways analysis of variance p = 0.039, t test corrigé par Bonferroni p<0.05 pour CD4 + et Kruskal-Wallis test p = 0.035, Mann-Whitney test corrigé par Bonferroni p< 0.001 pour CD8 + ) par conséquent le rapport CD4/CD8 du Groupe 2 a été significativement plus bas par rapport au Groupe 3 (Kruskal-Wallis test p = 0.014; Mann-Whitney test corrigé par Bonferroni p = 0.013). Aucune autre différence significative entre les trois groupes n’a été observée, en particulier avec le Groupe 1 (formes atrophiques-érosives) dont il faut signaler que le 40% des sujets sont porteurs d’une hépatopathie chronique souvent due au virus de l’hépatite C. En conclusion la différence des résultats entre les groupes 1 et 2 ne permet pas d’affirmer l’existence d’une pathogénie différente entre les formes atrophiques-érosives et les formes en réseaux ou en plaques, elle est en accord avec les précédentes études en histo-immunochimie. Il est possible que la diminution des lymphocytes CD4 + soit secondaire au déplacement de cette population cellulaire du compartement vasculaire de la muqueuse affectée par le lichen plan.

Hepatitis C virus infection and lichen planus: a systematic review with meta-analysis

Oral Diseases (2010) doi: 10.1111/j.1601-0825.2010.01670.x Objective: Hepatitis C virus (HCV) is one of the major causes of chronic liver disease worldwide but its morbidity is also due to a variety of extra-hepatic manifestations including mixed cryoglubulinemia, non-Hodgkin lymphoma, diabetes, porphyria cutanea tarda and lichen planus. The aims of this study were to conduct a systematic review and a meta-analysis on the prevalence of HCV in lichen planus patients and on the prevalence of lichen planus in chronic HCV infection. Materials and Method: Bibliographic searches were conducted in several electronic databases. Pooled data were analysed by calculating odds ratios, using a random effects model. Results and Conclusions: Thirty-three studies comparing the seroprevalence of HCV in lichen planus patients and six reporting the prevalence of lichen planus in patients with HCV infection were included in the meta-analysis. The summary estimate showed that LP patients have significantly higher risk (odds ratio 4.85; 95% confidence interval 3.58-6.56) than controls of being HCV seropositive. A similar odds ratio of having lichen planus was found among HCV patients (4.47; 95% confidence interval 1.84-10.86). Sub-analyses indicated that variability of HCV/lichen planus association seemed only partially depending on geographic effect

Griscelli syndrome type 2: long-term follow-up after unrelated donor bone marrow transplantation

Griscelli syndrome (GS) is a rare autosomal recessive disease characterized by silvery hair ('partial albinism'). Three forms exist; GS type 2 (GS2), the most common one, is characterized by severe primary immunodeficiency with acute episodes of hemophagocytic lymphohistiocytosis (HLH) which may be fatal in the absence of hematopoietic stem cell transplantation. A 5-year-old boy with HLH was referred to us because of silvery-gray hair present since birth. Abnormal pigment clumps were observed in the medulla of hair shafts on light microscopy. Electron microscopy of a skin biopsy revealed melanosomes in melanocytes, but not in keratinocytes. Leukocytes were devoid of intracytoplasmic granules on blood smear. Neurological signs were absent. Genotyping revealed a homozygous haplotype for polymorphic markers linked to the RAB27A locus, but no RAB27A mutation. A diagnosis of GS2 was established. The patient received bone marrow transplantation (BMT) from an unrelated donor, and after 72 months he did not show relapse of HLH. The long, uneventful follow-up supports the use of BMT from an unrelated donor if transplantation from a relative is not possible

Isolated meniscotibial ligament rupture. The medial meniscus “belt lesion”

Ramp lesions play a major role in both anteroposterior and rotational instability following anterior cruciate ligament rupture. The meniscotibial ligament (MTL) is the most important structure to repair and is the primary stabilizer of the posterior horn of the medial meniscus. The posteroinferior insertion of the MTL on the posterior horn of the medial has been described, forming a posterior “belt.” Isolated MTL lesion diagnosis can be challenging, as the absence of a meniscocapsular ligament lesion prevents its correct visualization through transnotch vision. This article details a tech- nique to diagnose and repair the “belt lesion” of the medial meniscus

Lichen planus and Hepatitis C: a case-control study

BACKGROUND: The association of lichen planus with hepatitis C (HCV) has been widely reported in the literature. However, there are wide geographical variations in the reported prevalence of HCV infection in patients with lichen planus. This study was conducted to determine the frequency of hepatitis C in Iranian patients with lichen planus at Razi hospital, Tehran. METHODS: During the years 1997 and 1998, 146 cases of lichen planus, 78 (53.1%) women and 69 (46.9%) men were diagnosed. They were diagnosed on the basis of the usual clinical features and, if necessary, typical histological findings. The patients were screened for the presence of anti-HCV antibodies by third generation ELISA and liver function tests. We used the results from screening of blood donors for anti HCV (carried out by Iranian Blood Transfusion Organization) for comparison as the control group. RESULTS: Anti-HCV antibodies were detected in seven cases (4.8%). This was significantly higher than that of the blood donors' antibodies (p < 0.001). The odds ratio was 50.37(21.45–112.24). A statistically significant association was demonstrated between erosive lichen planus and HCV infection. Liver function tests were not significantly different between HCV infected and non-infected patients. CONCLUSION: HCV apears to have an etiologic role for lichen planus in Iranian patients. On the other hand, liver function tests are not good screening means for HCV infection

TERT Extra-Telomeric Roles: Antioxidant Activity and Mitochondrial Protection

Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase holoenzyme, which adds telomeric DNA repeats on chromosome ends to counteract telomere shortening. In addition, there is evidence of TERT non-canonical functions, among which is an antioxidant role. In order to better investigate this role, we tested the response to X-rays and H2O2 treatment in hTERT-overexpressing human fibroblasts (HF-TERT). We observed in HF-TERT a reduced induction of reactive oxygen species and an increased expression of the proteins involved in the antioxidant defense. Therefore, we also tested a possible role of TERT inside mitochondria. We confirmed TERT mitochondrial localization, which increases after oxidative stress (OS) induced by H2O2 treatment. We next evaluated some mitochondrial markers. The basal mitochondria quantity appeared reduced in HF-TERT compared to normal fibroblasts and an additional reduction was observed after OS; nevertheless, the mitochondrial membrane potential and morphology were better conserved in HF-TERT. Our results suggest a protective function of TERT against OS, also preserving mitochondrial functionality