Search PubMed⌕ Search

Biomedical subjects

P G Calzavara-Pinton

Publications and source records attributed to P G Calzavara-Pinton.

At least 19 recordsLinked to original sources

A comprehensive overview of photodynamic therapy in the treatment of superficial fungal infections of the skin.

Photodynamic therapy (PDT) is a two-step procedure, involving the topical or systemic administration of a photosensitizer followed by selective illumination of the target lesion with visible light, which triggers the oxidative photodamage and subsequent cell death within the target area. In dermatology, PDT has proven to be a useful treatment for a variety of malignant tumors and selected inflammatory diseases. In addition, PDT of several infective viral or bacterial skin diseases has been investigated. These investigations grew out of the positive findings of studies of another important use of PDT: that of disinfection of blood products. Up to now, little has been published concerning the application of PDT to fungi, probably due to the fact that research funding has been mainly directed towards blood disinfection, and these pathogens show a low risk of transfusion transmission. However, preliminary findings have demonstrated that dermatophytes and yeasts can be effectively sensitized in vitro by administering photosensitizers belonging to four chemical groups: phenothiazine dyes, porphyrins and phthalocyanines, as well as aminolevulinic acid, which, while not a photosensitizer in itself, is effectively metabolized into protoporphyrin IX. Besides efficacy, PDT has shown other benefits. First, the sensitizers used are highly selective, i.e., fungi were killed at combinations of drug and light doses much lower than that needed for a similar effect on keratinocytes. Second, all investigated photosensitizers lack genotoxic and mutagenic activity. Finally, the hazard of selection of drug resistant fungal strains was never reported. This paper intends to provide a comprehensive overview of investigative studies about the effects of PDT on yeasts and dermatophytes, and bring attention to this application of PDT which we believe very important in that skin mycosis is so common and PDT is not only cost-effective, but also has the advantages of being highly selective and avoiding the occurrence of drug resistant strains.

Animals↗

Polymorphism analysis of Epstein-Barr virus isolates of lymphoblastoid cell lines from patients with mycosis fungoides.

In order to determine whether there is an association between the presence of Epstein-Barr virus (EBV) and mycosis fungoides (MF) disease progression, PCR was performed to detect the EBV status of 20 MF patients; six EBV-positive patients were found. EBV variants may differ in their biological properties, such as their ability to transform cells; therefore, the ability of these variants to immortalize B cells in vitro was analysed. Six continuously growing cell lines were obtained from prolonged cultures of unstimulated peripheral blood mononuclear cells that were taken from the six EBV-positive patients with MF. In order to characterize the EBV strains, EBNA-2 and LMP-1/LMP-2 gene polymorphisms in the six cell lines were also analysed. All patients were followed up for 10 years and it was noticed that EBV-positive patients had a poor prognosis with rapid disease progression and high mortality rates, compared to EBV-negative patients. EBV may therefore constitute a co-factor that accelerates the progression of disease.

Aged↗

Photodynamic therapy of interdigital mycoses of the feet with topical application of 5-aminolevulinic acid.

BACKGROUND: Findings of in vitro studies have demonstrated that dermatophytes and yeasts can be effectively photosensitized after topical delivery of 5-aminolevulinic acid (ALA). This procedure, called photodynamic therapy (PDT), seems to lack mutagenic activity and hazard of selection of drug-resistant strains. METHODS: Twenty percent ALA preparation in Eucerin cream was applied under an occlusive dressing to skin lesions of nine patients with clinical and microbiological evidence of interdigital mycosis of the feet. After 4 h, lesions were irradiated with 75 J/cm(2) of broad-band red light. Interdigital lesions of the other foot served as control (treated with only light or only ALA). After 7 days from the first treatment, no further treatment was delivered if lesions were not clinically evident and direct microscopic examination was negative. Otherwise, three additional weekly treatments were delivered. Four weeks after the last treatment, patients had a final follow-up clinical and laboratory examination. RESULTS: Clinical and microbiological recovery was seen in six out of nine patients after one (four cases) or four (two cases) treatments. However, after 4 weeks, recurrences were seen in four patients. Overall tolerability was always good. CONCLUSION: Under the conditions employed in the present study, ALA-PDT had good therapeutic effects on interdigital mycosis of the feet. However, recurrences were quick. In vivo environmental conditions, i.e. temperature, humidity and pH of the interdigital skin, could induce a poor cell uptake of ALA and a deficient biosynthesis of photosensitizing protoporphyrin IX. In addition, the irregular tridimensional shape of this peculiar anatomical area could lead to a non-uniform delivery of light and/or ALA cream. However, the present results can stimulate further studies on the PDT of superficial skin mycoses.

Administration, Cutaneous↗

Photodynamic therapy using topical methyl 5-aminolevulinate compared with cryotherapy for actinic keratosis: A prospective, randomized study.

BACKGROUND: Actinic keratoses (AKs) are the most common premalignant tumors. Without treatment, a significant number of patients with AK will experience squamous cell carcinoma. Photodynamic therapy (PDT) using the new highly selective photosensitizer methyl 5-aminolevulinate is a promising new treatment modality for AK. OBJECTIVE: We investigated the complete response rates, cosmetic outcome, and patient satisfaction after photodynamic therapy (PDT) using methyl 5-aminolevulinate (Metvix) versus cryotherapy in the treatment of AKs. METHODS: Patients were randomized to receive either cryotherapy with liquid nitrogen spray or PDT using methyl 5-aminolevulinate cream 160 mg/g, 3 hours application time, and red light (75 J/cm(2)). RESULTS: Efficacy results from 193 patients with 699 lesions (92% face/scalp and 93% thin/moderately thick) were analyzed. Overall complete response rates after 3 months were 69% for PDT and 75% for cryotherapy. Both treatments gave higher response rates in thin lesions (PDT 75%, cryotherapy 80%). PDT gave better cosmetic results and higher patient satisfaction than cryotherapy. CONCLUSION: PDT using methyl 5-aminolevulinate is an attractive treatment option for patients with AK, with a response rate similar to that of cryotherapy, but with superior cosmetic results and high patient satisfaction.

Administration, Topical↗

Blisters on psoriatic lesions treated with TL-01 lamps.

BACKGROUND: Asymptomatic blisters on psoriatic plaques are an uncommon adverse effect of TL-01 (UVB narrow-band 312 nm) phototherapy. OBJECTIVE: We report 7 new cases aiming to clarify the pathogenesis. METHODS: Blisters were biopsied at different times after onset. Blood porphyrins and antibodies to nuclear antigens and the cell surface of keratinocytes were investigated. RESULTS: We observed 7 asymptomatic blistering eruptions strictly limited to recovering psoriatic plaques. Biopsies taken within 24 h showed junctional detachment and apoptotic necrosis of basal keratinocytes. After 48 and 72 h, the blisters were intraepithelial, due to basal cell regeneration, and were no longer evident at 96 and 120 h. Dermal inflammation was always mild. Direct immunofluorescence tests as well as stainings for p53 protein did not show substantial changes. Blood investigations were negative. CONCLUSIONS: TL-01 blisters are caused by the quick reduction of acanthosis and desquamation before defensive mechanisms, i.e. the increase in the thickness of the stratum corneum and pigmentation, develop. However, the pathogenetic mechanisms of apoptosis of keratinocytes remain unknown.

Adolescent↗

Incidence of antiperinuclear factor in patients with psoriatic arthritis.

Antiperinuclear factor (APF) is considered a disease marker of rheumatoid arthritis (RA) and its diagnostic value is obvious in patients who are seronegative for rheumatoid factor (RF) activity. We have evaluated APF positivites in 76 patients with psoriatic arthritis, 38 uncomplicated psoriatic patients, 119 patients with non-inflammatory rheumatic diseases (NIRD), 36 RF- and 123 RF + RA patients and 204 healthy controls. APFs were investigated with an indirect immunofluorescence (IIF) test using epithelial cells from human buccal mucosa as a substrate. 6/76 (7.9%) PA patients were APF+. The incidence was greater than in healthy controls (2/204; p < 0.01) and similar to the incidences in patients with uncomplicated psoriasis (1/38; p = NS) and patients with non-inflammatory rheumatic disease NIRD (5/119; p = NS). However, the incidence was much lower than in RF- (19/36; p < 0.001) as well as RF+ (111/123; p < 0.001) RA patients. Finally, we emphasise that 3 out of 6 APF positivities shown by PA patients were found in our 3 patients with pustolotic arthroosteitis, a new specific entity in the spectrum of PA.

Antibodies, Antinuclear↗

Antiperinuclear factor in psoriatic arthropathy.

BACKGROUND: Antiperinuclear factor (APF) is an autoantibody directed against (pro)-filaggrin molecules. OBJECTIVE: We evaluated whether APF determination is useful for the diagnosis of psoriatic arthritis (PA). METHODS: We determined APF titers in sera from patients with PA (n = 76), psoriasis vulgaris (n = 38), noninflammatory rheumatic diseases (NIRDs, n = 119), rheumatoid arthritis (RA, n = 159) both with negative (n = 36) and positive (n = 123) rheumatoid factor (RF) tests, as well as from 204 healthy controls. We used an indirect immunofluorescence test on epithelial cells from human buccal mucosa as a substrate. RESULTS: In patients with PA, 7.9% of the serum samples were APF-positive. The incidence was greater than in healthy controls (1.0%; P < .01), similar to those with uncomplicated psoriasis (2.6%; P = NS) and NIRDs (4.0%; P = NS), and lower than in RF-negative (52.7%; P < .001) and RF-positive (90.2%; P < .001) patients with RA. Three APF-positive patients with PA had symmetric joint involvement and 3 had pustulotic arthroosteitis. CONCLUSION: The APF test may be useful in differentiating PA from RA, and APF may be specific for two PA subgroups.

Antibodies, Antinuclear↗

Bath-5-methoxypsoralen-UVA therapy for psoriasis.

BACKGROUND: After oral intake, 5-methoxypsoralen (5-MOP) is as effective as 8-MOP for PUVA therapy for psoriasis, with a lower incidence of acute cutaneous side effects. OBJECTIVE: We compared bath-water delivery of 5-MOP and 8-MOP for photochemotherapy of psoriasis. METHODS: Twenty-two patients underwent phototesting with 0.0003% 5-MOP or 8-MOP aqueous solutions. Twelve patients with palmar psoriasis were studied with a side-to-side comparison, and 10 patients with recurrent plaque-type psoriasis were treated with one therapy or the other. RESULTS: Minimal phototoxic dose (MPD) values were 2.8 +/- 1.2 J/cm2 with 8-MOP and 2.0 +/- 1.2 J/cm2 with 5-MOP (p < 0.01). Both therapies cleared palmar lesions but 8-MOP required more UVA irradiation (46.3 +/- 21.0 J/cm2 vs 30.2 +/- 21.5 J/cm2; p < 0.01) and more exposures (21.0 +/- 6.0 vs 17.0 +/- 5.0; p = 0.02). Bath-5-MOP-UVA was also more effective in the treatment of plaque-type psoriasis (cumulative UVA doses, 56.8 +/- 39.2 vs 59.1 +/- 27.9 J/cm2; number of exposures, 20.0 +/- 5.7 vs 21.6 +/- 4.7), but these differences were not significant (p = NS). Patients developed an intense tan significantly earlier with 5-MOP than with 8-MOP (3.5 +/- 0.5 weeks vs 4.4 +/- 0.5 weeks; p < 0.01). CONCLUSION: Bath-5-MOP-UVA was more phototoxic than bath-8-MOP-UVA. It was more effective in the treatment of palmar psoriasis, whereas its greater pigmentogenic activity appeared to have an adverse effect on therapeutic effectiveness in the treatment of plaque-type psoriasis.

5-Methoxypsoralen↗

Efficacy and safety of stand-up irradiation cubicles with UVA metal-halide lamps (and a new filter) or UVA fluorescent lamps for photochemotherapy of psoriasis.

BACKGROUND: Metal-halide lamps (MHLs) and fluorescent lamps (FLs) are widely employed for PUVA therapy of psoriasis, but they have never been compared in a clinical trial. OBJECTIVE: We studied the irradiance, spectral power distribution, irradiation field and efficacy of two cabinets with standard FLs or MHLs with a new UVA filter. METHODS: The photophysical properties of the lamps were studied with a spectroradiometer. After phototesting, 22 patients with recurrent plaque type psoriasis were treated in a stand-up irradiation cubicle housing 27 standard FLs, and, at recurrence, in a cubicle with 15 MHLs. When indicated, lesions of the legs underwent supplementary exposures with small FL or MHL devices. RESULTS: MHLs had a greater emission in the longer UVA wavelengths than FIs. The MHL cubicle had a greater irradiance and a more uniform output along the vertical axis. Both cubicles were effective in a similar number of exposures. However, FLs were more phototoxic and lower cumulative UVA doses were administered although the total duration of exposures was longer. Eleven patients treated with FLs and 7 patients with MHLs required supplementary treatments of the legs. The number, cumulative UVA dose and total duration of these exposures were significantly greater with FLs. CONCLUSION: Cabinets with MHLs increase the number of patients treated in the same time period and reduce the number of patients needing supplementary treatments of the legs. Cumulative UVA doses are greater with MHLs, but their emission is prevalent in the less erythematogenic and carcinogenic longer UVA wavelengths.

Adolescent↗

Perspectives in cutaneous photodynamic sensitization.

The photodynamic therapy of cutaneous disease is developing more rapidly than that of other organs due to the accessibility of the skin to photosensitizers and light. The use of hematoporphyrin derivative, with its prolonged photosensitivity of normal skin, is gradually being replaced by a new generation of tetrapyrrolic photosensitizers. These are designed to absorb at longer wavelengths for deeper tissue penetration. Many also feature a greatly reduced photosensitizing potential of uninvolved skin. Another major development is the topical and systemic use of aminolevulinic acid for inducing the formation of endogenous porphyrins in cells which result in photosensitivity. This regimen is currently used quite extensively due to the easy availability of both drug and suitable light sources. However, continued investigation of the underlying mechanisms and their regulation will help to improve this specific photodynamic regimen. Currently, researchers use a whole array of therapeutic regimens and schedules for the evaluation of treatment efficacy. A certain uniformity of both treatment parameters and evaluation criteria will help to improve more rapidly our understanding of photodynamic sensitization in skin disease. This will also help us to define the right place and targeting strategies for photodynamic therapy in dermatology.

Hematoporphyrin Derivative↗

Photodynamic therapy with systemic administration of photosensitizers in dermatology.

We have reviewed the results of clinical investigations into the use of photodynamic therapy (PDT) with intravenous injection of hematoporphyrin derivative (HpD), Photofrin (PF) and Sn-protoporphyrin (Sn-Pp) or oral administration of delta-aminolevulinic acid in the treatment of skin cancers and/or psoriasis. Bowen's disease was highly responsive, provided that adequate light and HpD or PF doses were delivered. In contrast, poor results were shown for squamous cell carcinoma, and the rates of complete response of basal cell carcinoma ranged between 0% and 100%. Treatment failures could be related to the delivery of low drug and/or light doses, but differences in the thickness and pigmentation of the treated lesions may play a relevant role. Good palliation was almost always achieved in patients affected by primary and secondary breast carcinomas, although complete eradication of tumors was very rare. PDT is a very promising treatment modality for both Mediterranean and HIV-related Kaposi's sarcoma, because it appears to be effective, can be repeated and is not associated with immunosuppressive activity or significant systemic toxicity. PDT of psoriasis with low doses of Sn-Pp, HpD or PF plus UVA light and PF plus 630 nm light proved to be effective and was associated with mild, dose-related and reversible photosensitivity.

Aminolevulinic Acid↗

Repetitive photodynamic therapy with topical delta-aminolaevulinic acid as an appropriate approach to the routine treatment of superficial non-melanoma skin tumours.

Photodynamic therapy (PDT) with topical delta-aminolaevulinic acid (ALA) is considered as a valuable tool for treating non-melanoma skin tumours, but there is no consensus about the methods of treatment, where they should be used and the rates of complete responses. This study reports the treatment of 50 actinic keratoses (AKs), 23 superficial basal cell carcinomas (BCCs), 30 nodular BCCs, 4 pigmented BCCs, 12 superficial squamous cell carcinomas (SCCs), 6 nodular SCCs, 6 Bowen's diseases and 4 keratoacanthomas (KAs). A 20% ALA emulsion was applied under an occlusive dressing for 6-8 h and the skin was then irradiated with 630 nm light from a dye laser. Treatments were delivered every other day until complete clinical disappearance of the lesions was observed. ALA-PDT was interrupted in the case of a partial response if, after two additional treatments, no further improvement was observed. All AKs (50/50), superficial BCCs (23/23), Bowen's diseases (6/6) and KAs (4/4) showed a complete response. In addition, 91.6% (11/12) superficial SCCs, 80.0% (24/30) nodular BCCs and 66.7% (4/6) nodular SCCs responded completely to the treatment. All 4 pigmented BCCs were resistant to the therapy. Some (59) of the treated areas that appeared completely responsive were excised for serial histopathological examination and the remaining 63 were followed-up for 24-36 months (median value, 29 months). Comprehensively, the rates of complete responses decreased after taking into consideration the results of these histological examinations and the long-term follow-up. The final response rates are as follows: 84.0% (42/50) AKs, 86.9% (20/23) superficial BCCs, 50% (15/30) nodular BCCs, 83.3% (10/12) superficial SCCs and 33.3% (2/6) nodular SCCs. The rates of complete responses of Bowen's diseases and KAs remained at 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Angiokeratoma corporis diffusum and arteriovenous fistulas with dominant transmission in the absence of metabolic disorders.

BACKGROUND: A three-generation family with members affected by angiokeratoma corporis diffusum (ACD) and arteriovenous fistulas of the legs is described. Our purpose was to investigate possible lysosomal storage defects previously described in association with ACD. OBJECTIVE: Results of physical examination of both affected and unaffected family members were otherwise normal as was the life span. The inheritance pattern of both ACD and arteriovenous fistula traits was autosomal dominant, with variable expressivity and incomplete penetrance. Microscopic examination of ACD lesions showed dilated capillaries without vacuolation of cells. Ultrastructural studies failed to reveal lysosomal abnormalities. Normal levels of alpha-galactosidase, beta-galactosidase, alpha-fucosidase, and alpha-sialidase were detected in peripheral blood leukocytes and skin fibroblasts. CONCLUSIONS: The association of autosomal dominant ACD and arteriovenous fistulas might represent a novel syndrome. However, pathogenesis of these lesions remains unknown.

Adolescent↗

Safety and effectiveness of an aggressive and individualized bath-PUVA regimen in the treatment of psoriasis.

BACKGROUND: The optimal therapeutic regimen of bath-PUVA therapy of psoriasis is still under debate. OBJECTIVE: We investigated the safety and efficacy of an aggressive and individualized bath-PUVA regimen. METHODS: Two closely matched groups of 22 psoriatic patients were treated either with 30-min baths in 0.0003% 8-methoxypsoralen (8-MOP) aqueous solution or oral administration of the drug. According to the standard European regimen, treatments were delivered 4 times a week starting with the minimal phototoxic dose. RESULTS: Complete clearing or marked improvement was observed in all the patients. However, with bath-PUVA, the same therapeutic effect required smaller cumulative UVA doses (39.3 +/- 15.8 vs. 123.8 +/- 39.9 J/cm2) and lower numbers of exposures (15.2 +/- 4.4 vs. 20.6 +/- 4.2). Both differences were significant at the 0.01 level (Student's t test). Gastro-intestinal side-effects were of course restricted to oral 8-MOP. The incidences of burns and pruritus were similar. CONCLUSION: Using an aggressive and individualized schedule, bath-PUVA therapy showed a greater efficacy than oral PUVA therapy while being just as safe.

Administration, Oral↗

Ocular side effects of PUVA-treated patients refusing eye sun protection.

We have investigated short- and long-term ocular side effects of psoralen plus UVA (PUVA) therapy in 82 patients who refused to wear UVA blocking sunglasses after the treatments. They had received 321.7 +/- 328.8 J/cm2 of UVA in 148.8 +/- 113.9 exposures over 2-4 years. Results were compared with findings obtained in 749 patients who shielded their eyes. They received 402.6 +/- 302.2. J/cm2 of UVA in 167.8 +/- 136.9 treatments over 2-6 years. 20 patients refusing eye sun protection developed conjunctival hyperemia and 21 patients decreased lacrimation. Among patients who adequately protected the eyes, we observed 5 cases of conjunctival hyperemia and 1 case of decreased lacrimation. Lens opacities did not develop in any patient. Adequate eye sun-protection is thus needed to avoid acute toxicity of cornea and conjunctiva but lens opacities do not appear to be a side effect of long-term PUVA-therapy.

Adolescent↗

Comparison of narrow-band (311 nm) UVB and broad-band UVA after oral or bath-water 8-methoxypsoralen in the treatment of psoriasis.

BACKGROUND: There is a disparity between the absorption spectrum of 8-methoxypsoralen and the action spectrum for psoralen-sensitized erythema. In an action spectrum corrected for unsensitized reaction 313 and 365 nm have similar efficacies. OBJECTIVE: We evaluated the relative erythemogenic and antipsoriatic efficacy of narrow-band (311 nm) UVB with and without prior psoralen exposure. We also compared the effects of narrow-band UVB and broad-band UVA after oral and bath-water psoralen exposure. METHODS: Patients with psoriasis underwent half-side comparison studies. In one group the therapeutic efficacy of 311 nm UVB with and without oral psoralen was assessed. The second group received UVA and 311 nm UVB after oral psoralen. The third group was exposed to both radiation sources after bath-water exposure. RESULTS: The erythemogenic, pigmentogenic, and therapeutic efficacy of 311 nm was increased by oral psoralen. With systemic 8-methoxypsoralen, UVA was comparable to 311 nm UVB. After bath-water exposure, 311 nm was clearly superior to broad-band UVA. CONCLUSION: The efficacy of narrow-band 311 nm UVB can be enhanced by psoralen. Narrow-band 311 nm UVB is also effective after psoralen bath-water delivery.

Administration, Cutaneous↗