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Biomedical subjects

P Rubegni

Publications and source records attributed to P Rubegni.

At least 19 recordsLinked to original sources

A case of bullous tinea pedis with dermatophytid reaction caused by Trichophyton violaceum.

Summary The authors report a case of bullous tinea pedis caused by Trichophyton violaceum with dermatophytid reaction in a 26-year-old woman who had been in Africa. Diagnosis was based on mycological examination (direct microscope observation and culture). Recovery was achieved after systemic antimycotic therapy with itraconazole and topical imidazole for a month.

Adult↗

A case of Darier's disease successfully treated with topical tacrolimus.

Tacrolimus is a macrolide that inhibits T-cell activation. The most extensive experience with topical tacrolimus has been in treating atopic dermatitis but it has been used in various skin diseases, including Hailey-Hailey disease, with encouraging results. We report a case of extensive Darier's disease successfully treated with topical tacrolimus, after suspension of oral isotretrinoin due to major depression.

Administration, Topical↗

Dysplastic naevus vs. in situ melanoma: digital dermoscopy analysis.

BACKGROUND: To date, much confusion exists about the biological significance of dysplastic naevi and about the relationship between melanocytic dysplasia and clinical atypia. OBJECTIVES: To use a digital dermoscopy analyser with a series of 'borderline' pigmented skin lesions (i.e. dysplastic naevi and in situ melanomas) to find correlation between the studied variables and to determine their discriminating power with respect to histological diagnosis. METHODS: The pigmented skin lesions (n = 174) were histologically examined by three experienced dermatopathologists and identified as in situ melanomas (n = 38) and dysplastic naevi (n = 136). The system evaluated 48 parameters as possible discriminant variables, grouped into four categories: geometry, colours, textures and islands of colour. Once the lesions were analysed (stepwise discriminant analysis), sensitivity, specificity and accuracy were calculated. RESULTS: At the end of the stepwise procedure the percentage of cases classified correctly was 71.8%. Of 136 dysplastic naevi only 98 were classified correctly, while 27 of 38 in situ melanomas were recognized correctly. CONCLUSIONS: We conclude that there are so far no digital dermoscopic criteria that can clearly distinguish dysplastic naevi from in situ melanomas.

Dermoscopy↗

Extracorporeal photopheresis affects interleukin (IL)-10 and IL-12 production by monocytes in patients with chronic graft-versus-host disease.

BACKGROUND: Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic bone marrow transplantation. Extracorporeal photopheresis (ECP) has recently been introduced as an alternative treatment for cases of cGVHD refractory to conventional immunosuppressive treatment, but its mechanism of action is not yet clear. OBJECTIVES: To investigate in seven patients with cGVHD the effects of ECP on resistance of monocytes to apoptosis and on monocyte cytokine production. METHODS: We designed an in vitro model that could mimic the potential in vivo effect of reinfusion of peripheral blood mononuclear cells treated by ECP. The model was based on coculture of ECP-treated lymphocytes with untreated monocytes from the same patient. RESULTS: ECP did not accelerate spontaneous apoptosis of monocytes. However, ECP-treated monocytes produced increased amounts of interleukin (IL)-12. In contrast, IL-12 production by monocytes did not increase in cocultures, but IL-10 production was upregulated. CONCLUSIONS: These results suggest that reinfusion of large numbers of autologous apoptotic lymphocytes is significant for the therapeutic outcome of ECP through upregulation of IL-10, which is an immunosuppressive cytokine.

Adult↗

Role of extracorporeal photochemotherapy in patients with refractory chronic graft-versus-host disease.

Recent studies suggest that extracorporeal photochemotherapy (ECP) may be beneficial in patients with steroid-refractory chronic graft-versus-host disease (cGvHD). However, it is not yet clear whether certain conditions, such as age, mode of onset of cGvHD etc., influence clinical response and whether certain affected organs are more sensitive to ECP than others. We analysed the main clinical and laboratory parameters related to evolution of the disease in 32 steroid-refractory cGvHD patients, to identify any useful response predictors to ECP. ECP affected the course of the disease positively in 78% (25/32) of our cases.

Adult↗

Umbilical endometriosis in pregnancy: a case report.

To our knowledge, this is the first case reported in the literature of umbilical endometriosis in a pregnant woman. We report a case of umbilical endometriosis in a pregnant woman at 16 weeks of gestation. The patient revealed a reddish-brown polypoid nodule within the umbilical depression, with the typical history of monthly bleeding from the umbilicus. A nodule biopsy, testing of serum levels of CA-125 and a transabdominal ultrasound examination were performed. The diagnosis of endometriosis was confirmed by pathological examination. Serum levels of CA-125 were slightly increased and the pelvic ultrasound examination did not identify ovarian cysts of a possible endometriotic nature. The patient was also examined at 24 weeks' gestation, after delivery and in the late postpartum period. No therapy was given and the lesion resolved spontaneously 2 months after the biopsy was taken.

Adult↗

Mechanism of action of extracorporeal photochemotherapy in chronic graft-versus-host disease.

Chronic graft-versus-host disease (GvHD) affects 50% of long-term bone marrow transplant survivors and remains a cause of major long-term morbidity in these patients despite aggressive therapy. Extracorporeal photochemotherapy (ECP), considered as an effective treatment for patients with erythrodermic cutaneous T-cell lymphoma (CTCL), has recently been used successfully in the treatment of GvHD. One of the most intriguing aspects of ECP is its ability to induce two apparently opposite effects: activation of the immune system against neoplastic cells (as in CTCL) and downregulation of the activity of T-cell clones in autoimmune diseases (as in systemic sclerosis, systemic lupus erythematosus and pemphigus vulgaris) and autoallogeneic immune responses (as in GvHD and allograft rejection). Only a better and more complete understanding of the various mechanisms involved will enable this interesting new therapy to be made more effective and selective.

Apoptosis↗

ECP-treated lymphocytes of chronic graft-versus-host disease patients undergo apoptosis which involves both the Fas/FasL system and the Bcl-2 protein family.

Chronic graft-versus-host disease (cGVHD) is a severe and frequent complication of allogenic bone marrow transplantation which is often treated with extracorporeal photochemotherapy (ECP) with a positive clinical outcome in patients resistant to conventional protocols. The mechanism of action of ECP has not been fully elucidated, although several authors have reported that it is able to induce apoptosis. Using samples obtained from ten cGVHD patients, we sought to determine whether lymphocytes treated with ECP underwent apoptosis and, above all, the mechanisms involved. Lymphocytes at four stages were isolated: immediately before ECP, from the last buffy coat collected, after UV irradiation prior to reinfusion, and the day after ECP. When cultured for 48 h, lymphocytes treated with ECP underwent accelerated apoptosis (tested as annexin V binding cells and as intracellular histone-associated DNA fragments) in comparison with lymphocytes from the other samples. This enhanced programmed cell death could not be prevented by IL-2. Immediately after isolation, there was no difference in Bcl-2 or bax expression among the four different samples, or in Fas and FasL mRNA. However, when cultured, lymphocytes treated with ECP showed a rapid downregulation of Bcl-2, an upregulation of bax with an increased bax/Bcl-2 ratio, a decrease in bcl-2 mRNA and an increase in Fas. No changes were detectable in lymphocytes from the other samples. IL-2 and TNF-alpha production was not significantly different among lymphocytes from the four samples. In conclusion, in patients affected by cGVHD, ECP induced apoptosis of lymphocytes with the involvement of both the Fas/FasL system and the Bcl-2 protein family.

Adult↗

Different effects of interferon-alpha on melanoma cell lines: a study on telomerase reverse transcriptase, telomerase activity and apoptosis.

BACKGROUND: Although the antiproliferative and proapoptotic effects of interferon (IFN)-alpha are widely recognized, its antitumour mechanisms are not completely known. Recent studies indicate that the derepressed expression of the catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT), and telomerase activity (TA) are involved in the process of human carcinogenesis. Only a few studies have investigated the effects of IFN-alpha on hTERT and TA, with controversial results. Objectives To study the hTERT mRNA expression, TA and apoptosis in human melanoma cells treated with IFN-alpha. METHODS: Five human melanoma cell lines (Me665/2/21, Me665/2/60, HT-144, SK-Mel-28 and SK-Mel-5) were cultured in standard conditions and treated with 20000 IU mL-1 of human recombinant IFN-alpha-2b. Apoptosis was evaluated as hypodiploid DNA content determined by flow cytometry, caspase-3/7 activity by enzymatic assay, and poly(adenosine diphosphate-ribose) polymerase cleavage by Western blot analysis. IFN-alpha receptor (IFNA-R) and hTERT mRNA expression levels were evaluated by semiquantitative reverse transcription-polymerase chain reaction. TA was evaluated by a polymerase chain reaction-based telomerase repeat amplification protocol assay. RESULTS: Besides a variable degree of cell proliferation inhibition in all cell lines tested, we found different responses, ranging from no significant effects in SK-Mel-28 cells, to a high degree of apoptosis with no hTERT mRNA expression and TA modification in HT-144 cells, and induction of apoptosis, along with decrease in hTERT mRNA expression and TA in Me665/2/21 cells. No induction of apoptosis was observed in SK-Mel-5 and Me665/2/60 cells, although an early decrease in hTERT mRNA expression, and a minor increase of both hTERT mRNA expression and TA were found, respectively. CONCLUSIONS: Our results suggest that the effects of IFN-alpha on hTERT and TA can result from the induction of apoptosis, but they can also occur through a direct modulation of hTERT. We hypothesize that, depending on the cellular context rather than the IFNA-R status of the targeted cells, IFN-alpha can elicit an apoptotic cell death; furthermore, different pathways of apoptosis, not necessarily involving telomerase, can be put into motion.

Apoptosis↗

Encephalocraniocutaneous lipomatosis (Haberland syndrome) with bilateral cutaneous and visceral involvement.

Encephalocraniocutaneous lipomatosis, or Haberland syndrome, is a rare congenital neurocutaneous disease. It is characterized clinically by unilateral lipomatous hamartomata of the scalp, eyelid, and outer globe of the eye, ipsilateral porencephalic cysts with cortical atrophy, cranial asymmetry, marked developmental delay and mental retardation. This syndrome should be distinguished from other mosaic neurocutaneous phenotypes such as as Delleman syndrome, Schimmelpenning syndrome, Goltz syndrome, Goldenhar syndrome and Proteus syndrome. Here we report a case of Haberland syndrome with bilateral involvement which underscores the extreme heterogeneity of clinical presentation of this and related syndromes.

Biopsy↗

Extracorporeal photochemotherapy in the treatment of eosinophilic fasciitis.

BACKGROUND: Eosinophilic fasciitis (EF) is a rare connective tissue disorder characterized clinically by symmetrical swelling, induration and thickening of the skin and histologically by thickening of the fascia with chronic inflammatory infiltrate containing eosinophils. The disease is classified in the spectrum morphea/systemic sclerosis and treated with systemic steroids and other immunosuppressant drugs. OBJECTIVE: The purpose of this study was to use extracorporeal photochemotherapy (ECP) in patients with EF to evaluate the effectiveness of this therapy. SUBJECTS AND METHODS: Three patients affected by EF were treated with ECP because they failed to respond or with contraindications to immunosuppressant treatment. The patients underwent ECP with a UVAR XTS apparatus. Subjects were treated on two consecutive days at 2-week intervals for the first 3 months and thereafter every 4 weeks on the basis of clinical response. The patients were assessed before therapy and then monthly by means of a clinical score. Changes in affected areas were evaluated at predetermined points by computerized skin elastometry (Cutometer SEM 474). RESULT: After 1 year of therapy we found considerable improvement of clinical parameters in two cases. There was less striking improvement in the other case. These clinical results were confirmed by the elastometry measurements. All patients reported improved quality of life, which enabled a reduction in the dose of immunosuppressants. CONCLUSION: ECP emerged as a safe and effective therapy in association with low doses of immunosuppressants in our three patients. A randomized comparative multicentre study between ECP as single therapy and ECP plus immunosuppressants and conventional therapies is required to firmly establish photopheresis as a possible basic treatment to combine with conventional therapies for EF.

Adrenal Cortex Hormones↗