Seven novel COL7A1 mutations identified in patients with recessive dystrophic epidermolysis bullosa from Mexico.

Recessive dystrophic epidermolysis bullosa (RDEB; OMIM #226600) is one of the most devastating subtypes of epidermolysis bullosa, a group of skin and mucous membrane blistering disorders often associated with extracutaneous manifestations. RDEB is caused by mutations in COL7A1, the gene encoding type VII collagen (C7), and to date over 700 different mutations in the 8835 nucleotides constituting the open reading frame or adjacent exon-intron boundaries of COL7A1 have been described. We used targeted next-generation sequencing to identify seven previously unreported mutations in a cohort of 17 Mexican patients who were diagnosed with RDEB based on clinical presentation and immunoepitope mapping. Our study expands the spectrum of mutations identified in this cohort, including those suitable for emerging therapies reliant on precise genotyping.

Clinical features of gingival lesions in patients with dystrophic epidermolysis bullosa: a cross-sectional study.

BACKGROUND: Gingival lesions in patients with dystrophic epidermolysis bullosa (DEB) are a common manifestation. However, their clinical features, frequency and severity are currently unknown. METHODS: Forty-five DEB patients were assessed by an oral medicine specialist, who analysed the presence/absence of four clinical signs (erythema, erosion/ulcer, atrophy, blister) on free and attached gingiva, using the Epidermolysis Bullosa Oropharyngeal Severity score. RESULTS: Twenty-eight (62.2%) out of 45 DEB patients showed different types of gingival lesions, whose presence/absence and total frequency/distribution were not significantly different between males and females (p=0.087 and p=0.091, respectively). Erythema was the most prevalent lesion (66.2%) and the recessive DEB severe generalized (RDEB-sev gen) reached the highest median disease activity score. A significant correlation was observed between the DEB subtypes and the disease activity median score (p<0.001), but not between age and total disease activity score in each group of DEB (p>0.05). Lastly, logistic regression showed that only gender (p=0.031) and RDEB-sev gen (p=0.001) were risks factors for the presence of gingival lesions. CONCLUSIONS: Gingival lesions in DEB patients are a relatively common entity and may have multiple clinical aspects, emphasizing the need for thorough attention and awareness among dentists.

Genotype-oropharyngeal phenotype correlation in Mexican patients with dystrophic epidermolysis bullosa.

Previous investigations have attempted to correlate the genotype with the cutaneous phenotype in patients with epidermolysis bullosa (EB), but never with the oropharyngeal phenotype. Seventeen dystrophic EB (DEB) patients were genotyped for COL7A1 gene mutations and divided into five distinct groups. Oropharyngeal disease severity was assessed with the Epidermolysis Bullosa Oropharyngeal Severity (EBOS) score by an oral medicine specialist. The genotype-phenotype correlation was calculated by Kruskal-Wallis analysis of variance using the Mann-Whitney test, applying the Bonferroni correction. The most severe oropharyngeal phenotype was found in the group with the 2470insG/3948insT mutation, with a mean disease severity score of 18.50 ± 2.12; the mildest was found in the 6862del16 mutation group, with a mean disease severity score of 0.57 ± 1.13. The most significant difference in median score was found in the total score (P = 0.009), followed by tongue (P = 0.02) and upper lip (P = 0.021), but no correlation was found between disease severity and the groups (P>0.005, after Bonferroni correction). Multiple comparisons among the five different genotypic groups revealed no statistically significant genotype-oropharyngeal phenotype correlation; it was not possible to establish which group was more severe, or to associate a specific mutation to a specific oropharyngeal phenotype.

[The United Nations conventions on the rights of persons with disabilities: which strategies for protection at work?]. / La convenzione O.N.U. sui diritti delle persone con disabilità: quali strategie per la tutela sul lavoro?

More than 15% of the world's population lives with some form of moderate or severe disabilities, a growing percentage due to aging population as well as to the global increase of chronic diseases. The United Nations approved, in December 2006, the "Convention on the Rights of Persons with Disabilities" which dealt with the theme "work and employment". It prohibited discrimination on the grounds of disability with regard to health and safety at work, ensuring safe and healthy working conditions including protection from harassment. The most important expectation for the UN Convention, ratified in Italy by law 18/2009, is the guarantee that disable people in the workplaces are provided with "reasonable accomodation". This term refers to modifications and adaptations which are necessary and appropriate, that do not foresee excessive costs, to be taken, where necessary, to ensure even workers with disabilities the enjoyment and exercise of all their rights.

Adjuvant triamcinolone acetonide injections in oro-pharyngeal pemphigus vulgaris.

BACKGROUND: High-potency topical and perilesional/intralesional corticosteroids are becoming increasingly useful as adjuvant to treat autoimmune blistering diseases. OBJECTIVE: We sought to evaluate the role of perilesional/intralesional triamcinolone acetonide (PITA) injections in reducing the time for first complete clinical remission and the total amount of systemic corticosteroids in oro-pharyngeal pemphigus vulgaris (OPV) patients, and also the compliance of PITA injections, in terms of satisfaction, pain and discomfort. METHODS: Thirty-five OPV patients were treated with conventional immunosuppressive therapy (CIST) and received high potency topical corticosteroids (clobetasol and/or methylprednisolone) and/or PITA injections. Patients were grouped as follows: (i) a group of 16 patients was treated with PITA injections and (ii) a group of 19 patients without PITA injections. RESULTS: Sixteen patients treated with PITA injections and 19 without PITA injections reached complete clinical remission within 126.6 days (SD: 41; 95% CI: 104.7-148.8) and 153.2 days (SD: 97.4; 95% CI: 106.2-200.1) (P = 0.4) respectively. The total amount of corticosteroids in patients treated with PITA and without PITA was 4894 mg (SD: 2832; 95% CI: 3385-6403) and 5312 mg (SD: 4009; 95% CI: 3380-7245) (P = 0.4) respectively. Patients treated with PITA reported a satisfaction score significantly higher than pain (P = 0.0007) and discomfort score (P = 0.0006). CONCLUSION: Perilesional/intralesional triamcinolone acetonide injections seems to represent a helpful clinical tool to successfully join CIST, in terms of shortening the time of complete clinical remission, reducing the total amount of corticosteroids and obtaining an acceptable compliance.

Oral pemphigus.

Pemphigus is a group of potentially life-threatening autoimmune diseases characterized by cutaneous and/or mucosal blistering, due to the presence circulating IgG antibodies directed against desmoglein 1 and 3 (Dsg 1 and 3). Differences in the particular distribution of these result in different clinical manifestations of the disease. The most common variant is pemphigus vulgaris (PV). There is a fairly strong genetic background to pemphigus with linkage to HLA class II alleles and ethnic groups such as Ashkenazi Jews and those of Mediterra-nean and Indian origin are especially liable. Oral lesions are commonly characterized by the presence of vesiculobullous and ulcerative lesions. Diagnosis is achieved via three different parameters: perilesional tissue biopsy, histological and immunological examinations. Serum autoantibodies to either Dsg1 or Dsg3 are best detected using both normal human skin and monkey esophagus or by enzyme-linked immunosorbent assay. The main aim of treatment is to reduce inflammatory re-sponse and autoantibody production, in order to achieve disease remission in a short time. Before the advent of corticosteroids, PV was typically fatal due to dehydration or secondary systemic infections. Current treatment is largely based on systemic immunosuppression using corticosteroids, with azathioprine or other adjuvants or alternatives. Nonetheless, newer therapies, such as intravenous immunoglobulins (IVIg) or anti-CD20 monoclonal antibodies (Rituximab), with potentially fewer adverse effects also appear promising.

Analysis of thromboembolic risk related to high-dose intravenous immunoglobulin treatment: a preliminary clinical study of 10 patients with autoimmune mucocutaneous blistering diseases.

BACKGROUND: Intravenous immunoglobulin (IVIg) treatment is a well-known treatment that has been used successfully in a broad spectrum of autoimmune diseases. Currently no data are available in the literature about the role of IVIg in the pathogenesis of thromboembolic events in patients with autoimmune blistering diseases refractory to conventional immunosuppressive treatment. AIM: To determine the relationship between IVIg and thromboembolism in patients with autoimmune blistering diseases and to establish a protocol to deal with the thromboembolic risk. METHODS: In our preliminary clinical study, 10 patients with autoimmune blistering diseases underwent IVIg cycles to a total of 133 cycles in all (total number of infusions in the patient group: 399), at a standard dose of 2 g/kg/infusion accompanied by an accurate and a complete clinical and laboratory screening for thromboembolism. Preventive measures, such as hydration before and after IVIg, and administration of 100 mg of acetyl salicylic acid (aspirin) or 1000 IU of subcutaneous heparin calcium per day for 3 weeks, were introduced to reduce the thromboembolic risk. RESULTS: Throughout the 2 years of IVIg treatment, no patient developed a superficial and/or deep venous or arterial thrombosis, even though some of the patients had underlying thromboembolic risk factors and had tested positive for some congenital and acquired thrombophilia markers. CONCLUSIONS: Our results indicate that thromboembolic events are uncommon, despite the presence of risk factors. However, as these disorders are very rare and the percentage of nonresponder patients is very low, further investigations are needed to better understand whether IVIg alone is able to trigger these fatal events in blistering disorders.

[Development of an educational programme for schools to promote the awareness on child labour]. / Sviluppo di un percorso formativo per le scuole orientato alla conoscenza del lavoro minorile.

The main aim of the ISPESL project "Child Labour: to know in order to take action" is to introduce the subject of the problem of child labour in primary schools. This is done through pedagogical tools and communication methods, using the child's curiosity and point of view as a starting point and giving support to the child as he/she expresses his feelings, messages and emotions and at the same time, develops his own reaction to the problem. This project has been developed within the activities of ISPESL as WHO Collaborating Center and addressed to all the reference figures interacting with school such as teachers, educators and headmaster, but also families and local Institutions who promote understanding and awareness on child labour. The project aims at giving a general picture of the phenomenon, by focusing on the multiple and complex causes affecting the physical and psychosocial well-being of children and on fostering the increase of awareness among children on child labour issues. Observation and investigation tools will be developed and used in specific training modules suited to the cultural and geographic framework of each field of teaching, in order to allow the children to acknowledge and express their better awareness on child labour.

[Health risks associated with child labor: activities and proposals of WHO collaboration centers]. / Rischi per la salute connessi al lavoro minorile: attività e proposte dei centri di collaborazione dell'OMS.

Child labour should be analyzed with regard to the main frameworks where it arises: particularly, the small family based enterprises in agricultural, hospitality and restaurateurs' sectors play a leading role. In these contexts the child can underestimate the risks related to the carried out work activity and assimilate the work background to the family background. In spite of the national thorough regulations on child labour, the network of WHO Collaborating Centres is working to develop a common awareness in order to evaluate, communicate and prevent the occupational health and safety risks for children, at national and international level.

[Importance of endocervical cells in the diagnosis of CIN]. / Importanza delle cellule endocervicali nella diagnosi di CIN.

BACKGROUND AND AIM: The authors performed a comparative study to define the role played by the presence of endocervical cells on the smear in the correct diagnosis of CIN. METHODS: The study was performed from January to December 1996 at the Clinic of Obstetrics and Gynecology of the Second University of Naples and involved 67 women with a histological diagnosis of CIN made in the two previous months of the study. The smears taken earlier were re-examined to assess the endocervical component regarding columnar and metaplastic cells and a comparison was made between smears which were CIN-positive and negative. RESULTS: The difference between positive and negative CIN smears was statistically non-significant for columnar cells (66% vs 56%), unlike the findings for metaplastic cells (82% vs 61%). This demonstrated that CIN smears are more likely to include metaplastic cells compared to negative smears and the two types of smear do not differ significantly with regard to columnar cells. CONCLUSIONS: In order to make a cytological diagnosis of CIN, attention must predominantly be focused on the metaplastic component of endocervical cells.

Phase II study of cisplatin and vinorelbine as first-line chemotherapy in patients with carcinoma of the uterine cervix.

PURPOSE: To evaluate the activity and toxicity of the combination of cisplatin (80 mg/m2 day 1) and vinorelbine (25 mg/m2 days 1 and 8) in patients with carcinoma of the uterine cervix that has not been previously treated with chemotherapy. PATIENTS AND METHODS: Fifty patients with cervical cancer were enrolled onto this study (27 stage IB-III, 23 stage IVB-recurrent). A two-stage optimal Simon design was applied. Thirteen responders of 29 treated patients were required to proceed beyond the first stage, and 28 responders were needed overall. RESULTS: Hematologic toxicity was mild, with neutropenia being the most frequent side effect. Nonhematologic toxicity was frequent but never severe; one patient had grade 3 peripheral neurotoxicity. Objective responses were recorded for 32 patients (64%): 11 patients (22%) achieved a complete response (CR) and 21 patients (42%) achieved a partial response (PR). The response rate was 81.5% in patients with IB-III stage (25.9% CR rate) and 43.5% in patients with IVB-recurrent disease (17.4% CR rate). Responses were seen both in stage IVB patients (one CR and two PRs, for an overall rate of 37.5%) and in patients with recurrent disease (three CRs + four PRs, for an overall rate of 46.7%). CONCLUSION: The combination of cisplatin and vinorelbine is an active regimen in the treatment of patients with early-stage and advanced carcinoma of the uterine cervix. The hematologic and nonhematologic toxicity of this combination is mild.

Primary malignant melanoma of the vagina: case report.

Primary vaginal melanoma is a very rare gynecological malignant tumor (less than 150 reported cases to-date). Prognosis is poor in spite of treatment. Due to the fact that only small groups of patients have been compared, conservative treatment has usually been recommended. In recent times, radical pelvic surgery has appeared to improve the chances of survival. We present an unusual case of primitive melanoma of the upper-third of the vagina with urethral and urinary bladder infiltration in a 47-year-old woman. Treatment consisted of preliminary pelvic bilateral lymphadenectomy, anterior exenteration, and urinary bladder reconstruction according to the Bricker technique. Four months after surgical treatment, liver metastases were found. Chemotherapy was initiated consisting of 8 cycles every 21 days of fotemustine 100 mg/m2 (day 1) and dacarbazine (DTIC) 250 mg/m2 (days 2-5). Interferon alpha-2-b, 3 MU thrice weekly, for the whole period of chemotherapy, was also administered. The patient is in partial remission one year after surgical treatment.