Journal of biological regulators and homeostatic agents
Discovery and pharmacological development of cyclosporine was conducted by Jean Borel and colleag... more Discovery and pharmacological development of cyclosporine was conducted by Jean Borel and colleagues in the 1970s. Cyclosporine is the first compound to inhibit the lymphocytes specifically and reversibly, and represents the prototype of a new generation of immunosuppressive drugs: the calcineurine inhibitors. Historical chronology of successes in clinical application of cyclosporine and development of solid-organ transplantation are retraced here, underscoring the converging timelines of this drug and these interventions. In 1978-79 the first successful results of the use of cyclosporine in kidney were reported. Cyclosporine was the first single drug able to control rejection. In 1982-83 first trials demonstrated the benefit from treatment with cyclosporine in kidney recipients compared to azathioprine and steroids. In the 1980s solid-organ transplantation entered the cyclosporine era with unhoped-for results in heart transplantation. The present review focuses also on cyclosporine...
Page 1. 14 Systemic Cyclosporin in the Treatment of Psoriasis Delia Colombo* and Antonino Di Piet... more Page 1. 14 Systemic Cyclosporin in the Treatment of Psoriasis Delia Colombo* and Antonino Di Pietro 1Ospedale Luigi Marchesi, Via Marchesi, Milano Italy 1. Introduction Cyclosporin was isolated in 1970, by Jean François ...
Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR) and has been shown to have... more Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR) and has been shown to have antineoplastic activity in addition to its use as an immunosuppressive agent for the prevention of organ transplant rejection. We report the use of everolimus for the compassionate treatment of four elderly, nontransplant patients presenting with multiple basal cell carcinomas (BCC). All patients had a long history of BCC, had refused surgery as a current treatment option, and did not respond to alternative treatments (including topical 5-fluorouracil and imiquimod). Patients were treated with oral everolimus (1.5-3.0 mg daily) for 12 months or longer: a complete and sustained response was seen in one case, and partial responses were seen in two other cases. Everolimus was well tolerated in these elderly patients. These promising preliminary data suggest that further dose-finding, controlled clinical studies are warranted to evaluate the antineoplastic effects of everolimus in patients affected by BCC who cannot or will not undergo surgery.
Journal of the American Academy of Dermatology, 2002
The involvement of Candida in the pathogenesis of chronic paronychia (CP) has never been proven, ... more The involvement of Candida in the pathogenesis of chronic paronychia (CP) has never been proven, even though this condition is commonly considered a type of Candida onychomycosis. The purpose of this study was to compare the efficacy of systemic antifungals (itraconazole or terbinafine) with a topical corticosteroid (methylprednisolone aceponate) in the treatment of patients with CP. The study involved 45 adult patients with CP. Medication was given in a randomized, double-blind and double dummy manner over 3 weeks. Patients were then followed for 6 weeks. Clinical and mycologic evaluations were performed at baseline, and at weeks 3 and 9. The efficacy measures included clinical and photographic evaluation. Of 48 nails treated with methylprednisolone aceponate, 41 were improved or cured at the end of the follow-up period. The statistical analysis showed a significant difference between the number of nails improved or cured by methylprednisolone aceponate and that of nails improved or cured with terbinafine (30 out of 57) or itraconazole (29 out of 64). Presence of Candida was not strictly linked to disease activity, and Candida eradication was associated with clinical cure in only 2 of the 18 patients who carried Candida at the beginning of the study. This study shows that topical steroids are more effective than systemic antifungals in the treatment of CP, and supports the view that CP is not a type of onychomycosis but a variety of hand dermatitis caused by environmental exposure.
Data about relapses of onychomycosis after treatment with the new systemic antifungals vary among... more Data about relapses of onychomycosis after treatment with the new systemic antifungals vary among the different studies, with figures ranging from 3 to 20% for terbinafine and from 21 to 27% for itraconazole, depending on the follow-up duration. To determine the prevalence of relapses of onychomycosis cured by terbinafine compared with that of onychomycosis cured by itraconazole. We followed up 47 patients whose toenail onychomycosis had been mycologically cured in an open randomized study comparing intermittent itraconazole treatment with continuous terbinafine treatment and intermittent terbinafine therapy. Patients were examined every 3 months for up to 3 years after the end of therapy. At each visit clinical and mycologic (direct microscopy and cultures) evaluations were performed. Eight of the 36 patients (22.2%) who completed the study had a relapse of onychomycosis during the follow-up period, including 2 patients of the terbinafine 250 mg group, 2 patients of the terbinafine 500 mg group and 4 patients in the itraconazole 400 mg group. As the original infection, the relapse was caused in all cases by Trichophyton rubrum. This study shows that 22.2% of patients with onychomycosis successfully treated with systemic antifungals experienced a relapse. The relapse rate increased from 8. 3% at month 12 to 19.4% at month 24 and to 22.2% at month 36. Relapses were more common in patients treated with pulse itraconazole (4/11) than in patients treated with continuous (2/12) or intermittent (2/13) terbinafine. Statistical analysis did not reveal any significant difference between relapse rates in the three groups.
... to Dynamic and Isometric Exercise in Men with Systemic Hypertension Stefano Savonitto, MD, Gi... more ... to Dynamic and Isometric Exercise in Men with Systemic Hypertension Stefano Savonitto, MD, Giovanni Cardellino, MD, Giulio Doveri, MD ... Valve Prosthesis Shimon A. Reisner, MD, Diana Rinkevich, MD, Walter Markiewicz, MD, Zvi Adier, MD, and Simcha Milo, MD Spontaneous ...
Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia, Jan 2, 2016
The SYNERGY study is an observational, multicenter Italian study, conducted in patients with diag... more The SYNERGY study is an observational, multicenter Italian study, conducted in patients with diagnosis of psoriatic arthritis (PsA) treated from at least 3 months with cyclosporine and aimed at assessing patients' seropositivity for viral infections and efficacy and safety of cyclosporine, administered as monotherapy or in combination with other systemic drugs in the routine clinical practice. The aim of this subanalysis of the SYNERGY study was to evaluate the effects of CsA as monotherapy only in PsA over 12 months of observation. Psoriasis was evaluated by Body Surface Area and the Psoriasis Area Severity Index (PASI). PsA was evaluated by number of swollen and tender joints, painful entheses and fingers with dactylitis, the Bath Ankylosing Spondylitis Activity Index (BASDAI) and by patients' and physicians' global assessment on a 10-point Visual Analogue Scale. Cyclosporine in monotherapy was effective in reducing all the measured disease parameters. The major indexe...
Clinical, cosmetic and investigational dermatology, 2016
Sex medicine studies have shown that there are sex differences with regard to disease characteris... more Sex medicine studies have shown that there are sex differences with regard to disease characteristics in immune-mediated inflammatory diseases, including psoriasis, in immune response and susceptibility to viral infections. We performed a post hoc analysis of the Observational Study of infectious events in psoriasis complicated by active psoriatic arthritis (SYNERGY) study in patients with psoriatic arthritis (PsA) treated with immunosuppressive regimens including cyclosporine, in order to evaluate potential between-sex differences in severity of disease and prevalence of viral infections. SYNERGY was an observational study conducted in 24 Italian dermatology clinics, which included 238 consecutively enrolled patients with PsA, under treatment with immunosuppressant regimens including cyclosporin A. In this post hoc analysis, patients' demographical data and clinical characteristics of psoriasis, severity and activity of PsA, prevalence of seropositivity for at least one viral i...
Sequential therapy may improve the efficacy and safety of single treatments for severe psoriasis.... more Sequential therapy may improve the efficacy and safety of single treatments for severe psoriasis. We compared sequential Cyclosporin A and narrow-band UVB phototherapy versus narrow-band UVB phototherapy alone. A group of 30 patients with severe psoriasis received 3 mg/kg/day Cyclosporin A for 4 weeks. Afterwards, Cyclosporin A was rapidly tapered and phototherapy begun. An additional 30 patients received phototherapy alone. Treatments were given until psoriasis cleared or until partial improvement was achieved without further amelioration despite another week of treatment. Both treatments were highly effective and well tolerated but sequential therapy was more effective in lesions of UV-shielded body areas; itching disappeared more quickly. The cumulative narrow-band UVB dosages and number of exposures were lower. No difference was seen at follow-up extended up to 9 months. Sequential therapy was well tolerated and allowed for the reduction of narrow-band UVB dosage and exposures, quick relief of itching and improvement of UV-shielded lesions.
Chronic urticaria (CU) is a common skin disorder with important repercussion on the quality of li... more Chronic urticaria (CU) is a common skin disorder with important repercussion on the quality of life and a relevant socioeconomic impact. CU is included among the skin diseases that exhibit a significant female preponderance, with an average female to male ratio of nearly 2- 4/1. In recent years, an ever-growing interest in gender medicine has been registered and the assessment of gender differences has increasingly become an attractive issue in clinical research. Unfortunately, there are only limited data relative to the study of CU in the perspective of gender medicine. However, apart from the predilection for females, an in-depth evaluation of the available literature shows the existence of other interesting gender-related differences in CU. The aim of this article is to review the current knowledge on gender differences in CU under different points of view, including pathophysiology, epidemiology, clinical and prognostic features, association with comorbidities, psychological asp...
Journal of biological regulators and homeostatic agents
Discovery and pharmacological development of cyclosporine was conducted by Jean Borel and colleag... more Discovery and pharmacological development of cyclosporine was conducted by Jean Borel and colleagues in the 1970s. Cyclosporine is the first compound to inhibit the lymphocytes specifically and reversibly, and represents the prototype of a new generation of immunosuppressive drugs: the calcineurine inhibitors. Historical chronology of successes in clinical application of cyclosporine and development of solid-organ transplantation are retraced here, underscoring the converging timelines of this drug and these interventions. In 1978-79 the first successful results of the use of cyclosporine in kidney were reported. Cyclosporine was the first single drug able to control rejection. In 1982-83 first trials demonstrated the benefit from treatment with cyclosporine in kidney recipients compared to azathioprine and steroids. In the 1980s solid-organ transplantation entered the cyclosporine era with unhoped-for results in heart transplantation. The present review focuses also on cyclosporine...
Page 1. 14 Systemic Cyclosporin in the Treatment of Psoriasis Delia Colombo* and Antonino Di Piet... more Page 1. 14 Systemic Cyclosporin in the Treatment of Psoriasis Delia Colombo* and Antonino Di Pietro 1Ospedale Luigi Marchesi, Via Marchesi, Milano Italy 1. Introduction Cyclosporin was isolated in 1970, by Jean François ...
Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR) and has been shown to have... more Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR) and has been shown to have antineoplastic activity in addition to its use as an immunosuppressive agent for the prevention of organ transplant rejection. We report the use of everolimus for the compassionate treatment of four elderly, nontransplant patients presenting with multiple basal cell carcinomas (BCC). All patients had a long history of BCC, had refused surgery as a current treatment option, and did not respond to alternative treatments (including topical 5-fluorouracil and imiquimod). Patients were treated with oral everolimus (1.5-3.0 mg daily) for 12 months or longer: a complete and sustained response was seen in one case, and partial responses were seen in two other cases. Everolimus was well tolerated in these elderly patients. These promising preliminary data suggest that further dose-finding, controlled clinical studies are warranted to evaluate the antineoplastic effects of everolimus in patients affected by BCC who cannot or will not undergo surgery.
Journal of the American Academy of Dermatology, 2002
The involvement of Candida in the pathogenesis of chronic paronychia (CP) has never been proven, ... more The involvement of Candida in the pathogenesis of chronic paronychia (CP) has never been proven, even though this condition is commonly considered a type of Candida onychomycosis. The purpose of this study was to compare the efficacy of systemic antifungals (itraconazole or terbinafine) with a topical corticosteroid (methylprednisolone aceponate) in the treatment of patients with CP. The study involved 45 adult patients with CP. Medication was given in a randomized, double-blind and double dummy manner over 3 weeks. Patients were then followed for 6 weeks. Clinical and mycologic evaluations were performed at baseline, and at weeks 3 and 9. The efficacy measures included clinical and photographic evaluation. Of 48 nails treated with methylprednisolone aceponate, 41 were improved or cured at the end of the follow-up period. The statistical analysis showed a significant difference between the number of nails improved or cured by methylprednisolone aceponate and that of nails improved or cured with terbinafine (30 out of 57) or itraconazole (29 out of 64). Presence of Candida was not strictly linked to disease activity, and Candida eradication was associated with clinical cure in only 2 of the 18 patients who carried Candida at the beginning of the study. This study shows that topical steroids are more effective than systemic antifungals in the treatment of CP, and supports the view that CP is not a type of onychomycosis but a variety of hand dermatitis caused by environmental exposure.
Data about relapses of onychomycosis after treatment with the new systemic antifungals vary among... more Data about relapses of onychomycosis after treatment with the new systemic antifungals vary among the different studies, with figures ranging from 3 to 20% for terbinafine and from 21 to 27% for itraconazole, depending on the follow-up duration. To determine the prevalence of relapses of onychomycosis cured by terbinafine compared with that of onychomycosis cured by itraconazole. We followed up 47 patients whose toenail onychomycosis had been mycologically cured in an open randomized study comparing intermittent itraconazole treatment with continuous terbinafine treatment and intermittent terbinafine therapy. Patients were examined every 3 months for up to 3 years after the end of therapy. At each visit clinical and mycologic (direct microscopy and cultures) evaluations were performed. Eight of the 36 patients (22.2%) who completed the study had a relapse of onychomycosis during the follow-up period, including 2 patients of the terbinafine 250 mg group, 2 patients of the terbinafine 500 mg group and 4 patients in the itraconazole 400 mg group. As the original infection, the relapse was caused in all cases by Trichophyton rubrum. This study shows that 22.2% of patients with onychomycosis successfully treated with systemic antifungals experienced a relapse. The relapse rate increased from 8. 3% at month 12 to 19.4% at month 24 and to 22.2% at month 36. Relapses were more common in patients treated with pulse itraconazole (4/11) than in patients treated with continuous (2/12) or intermittent (2/13) terbinafine. Statistical analysis did not reveal any significant difference between relapse rates in the three groups.
... to Dynamic and Isometric Exercise in Men with Systemic Hypertension Stefano Savonitto, MD, Gi... more ... to Dynamic and Isometric Exercise in Men with Systemic Hypertension Stefano Savonitto, MD, Giovanni Cardellino, MD, Giulio Doveri, MD ... Valve Prosthesis Shimon A. Reisner, MD, Diana Rinkevich, MD, Walter Markiewicz, MD, Zvi Adier, MD, and Simcha Milo, MD Spontaneous ...
Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia, Jan 2, 2016
The SYNERGY study is an observational, multicenter Italian study, conducted in patients with diag... more The SYNERGY study is an observational, multicenter Italian study, conducted in patients with diagnosis of psoriatic arthritis (PsA) treated from at least 3 months with cyclosporine and aimed at assessing patients' seropositivity for viral infections and efficacy and safety of cyclosporine, administered as monotherapy or in combination with other systemic drugs in the routine clinical practice. The aim of this subanalysis of the SYNERGY study was to evaluate the effects of CsA as monotherapy only in PsA over 12 months of observation. Psoriasis was evaluated by Body Surface Area and the Psoriasis Area Severity Index (PASI). PsA was evaluated by number of swollen and tender joints, painful entheses and fingers with dactylitis, the Bath Ankylosing Spondylitis Activity Index (BASDAI) and by patients' and physicians' global assessment on a 10-point Visual Analogue Scale. Cyclosporine in monotherapy was effective in reducing all the measured disease parameters. The major indexe...
Clinical, cosmetic and investigational dermatology, 2016
Sex medicine studies have shown that there are sex differences with regard to disease characteris... more Sex medicine studies have shown that there are sex differences with regard to disease characteristics in immune-mediated inflammatory diseases, including psoriasis, in immune response and susceptibility to viral infections. We performed a post hoc analysis of the Observational Study of infectious events in psoriasis complicated by active psoriatic arthritis (SYNERGY) study in patients with psoriatic arthritis (PsA) treated with immunosuppressive regimens including cyclosporine, in order to evaluate potential between-sex differences in severity of disease and prevalence of viral infections. SYNERGY was an observational study conducted in 24 Italian dermatology clinics, which included 238 consecutively enrolled patients with PsA, under treatment with immunosuppressant regimens including cyclosporin A. In this post hoc analysis, patients' demographical data and clinical characteristics of psoriasis, severity and activity of PsA, prevalence of seropositivity for at least one viral i...
Sequential therapy may improve the efficacy and safety of single treatments for severe psoriasis.... more Sequential therapy may improve the efficacy and safety of single treatments for severe psoriasis. We compared sequential Cyclosporin A and narrow-band UVB phototherapy versus narrow-band UVB phototherapy alone. A group of 30 patients with severe psoriasis received 3 mg/kg/day Cyclosporin A for 4 weeks. Afterwards, Cyclosporin A was rapidly tapered and phototherapy begun. An additional 30 patients received phototherapy alone. Treatments were given until psoriasis cleared or until partial improvement was achieved without further amelioration despite another week of treatment. Both treatments were highly effective and well tolerated but sequential therapy was more effective in lesions of UV-shielded body areas; itching disappeared more quickly. The cumulative narrow-band UVB dosages and number of exposures were lower. No difference was seen at follow-up extended up to 9 months. Sequential therapy was well tolerated and allowed for the reduction of narrow-band UVB dosage and exposures, quick relief of itching and improvement of UV-shielded lesions.
Chronic urticaria (CU) is a common skin disorder with important repercussion on the quality of li... more Chronic urticaria (CU) is a common skin disorder with important repercussion on the quality of life and a relevant socioeconomic impact. CU is included among the skin diseases that exhibit a significant female preponderance, with an average female to male ratio of nearly 2- 4/1. In recent years, an ever-growing interest in gender medicine has been registered and the assessment of gender differences has increasingly become an attractive issue in clinical research. Unfortunately, there are only limited data relative to the study of CU in the perspective of gender medicine. However, apart from the predilection for females, an in-depth evaluation of the available literature shows the existence of other interesting gender-related differences in CU. The aim of this article is to review the current knowledge on gender differences in CU under different points of view, including pathophysiology, epidemiology, clinical and prognostic features, association with comorbidities, psychological asp...
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