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Biomedical subjects

A Tosti

Publications and source records attributed to A Tosti.

At least 37 records · Page 2Linked to original sources

Innate immunity against hematological malignancies.

BACKGROUND: Allogeneic hematopoietic transplantation relies on T-cell alloreactions for engraftment and the GvL effect. In HLA haplotype-mismatched transplants, extensive T-cell depletion of the graft is essential to prevent GvHD. This raises the question of whether mismatched transplants exert any GvL effect, and whether it will ever be possible to reduce the intensity of preparative regimens. Natural killer (NK) cells are negatively regulated by MHC Class I-specific inhibitory receptors. Mismatched transplants may therefore trigger NK-cell alloreactivity. METHODS: The effects of NK-cell alloreactivity were evaluated in clinical transplantation and in murine transplant models. RESULTS: In clinical hematopoietic stem-cell transplants, HLA Class I disparities driving NK-cell alloreactions in the GvH direction eliminate AML relapse and graft rejection, while protecting patients from GvHD. In murine MHC mismatched transplant models, the pre-transplant infusion of donor-versus-recipient alloreactive NK cells conditioned the recipients to BMT, and reduced GvHD. DISCUSSION: NK-cell alloreactivity may thus provide a novel, powerful tool for enhancing the efficacy and safety of allogeneic hematopoietic transplantation.

Animals↗

Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype-mismatched hematopoietic transplants.

In human leukocyte antigen haplotype-mismatched transplantation, extensive T-cell depletion prevents graft-versus-host disease (GVHD) but delays immune recovery. Granulocyte colony-stimulating factor (G-CSF) is given to donors to mobilize stem cells and to recipients to ensure engraftment. Studies have shown that G-CSF promotes T-helper (Th)-2 immune deviation which, unlike Th1 responses, does not protect against intracellular pathogens and fungi. The effect of administration of G-CSF to recipients of mismatched hematopoietic transplants with respect to transplantation outcome and functional immune recovery was investigated. In 43 patients with acute leukemia who received G-CSF after transplantation, the engraftment rate was 95%. However, the patients had a long-lasting type 2 immune reactivity, ie, Th2-inducing dendritic cells not producing interleukin 12 (IL-12) and high frequencies of IL-4- and IL-10-producing CD4(+) cells not expressing the IL-12 receptor beta(2) chain. Similar immune reactivity patterns were observed on exposure of donor cells to G-CSF. Elimination of postgrafting administration of G-CSF in a subsequent series of 36 patients with acute leukemia, while not adversely affecting engraftment rate (93%), resulted in the anticipated appearance of IL-12-producing dendritic cells (1-3 months after transplantation versus > 12 months in transplant recipients given G-CSF), of CD4(+) cells of a mixed Th0/Th1 phenotype, and of antifungal T-cell reactivity in vitro. Moreover, CD4(+) cell counts increased in significantly less time. Finally, elimination of G-CSF-mediated immune suppression did not significantly increase the incidence of GVHD (< 15%). Thus, this study found that administration of G-CSF to recipients of T-cell-depleted hematopoietic transplants was associated with abnormal antigen-presenting cell functions and T-cell reactivity. Elimination of postgrafting administration of G-CSF prevented immune dysregulation and accelerated functional immune recovery.

Acute Disease↗

Studies on the photostability and in vitro phototoxicity of Labetalol.

The purpose of this study was to obtain information on the photochemical and phototoxic properties of Labetalol, a beta-blocker drug. Preliminary information on the drug photoreactivity was achieved using a flow system with a photochemical reactor on-line with a diode array detection system. Photophysical and photochemical investigations on the drug were performed in aqueous solutions at different pH values using spectrophotometric and fluorimetric methods; the photodegradation quantum yield was found to be 2.7 x 10(-3) at pH 5.8 and 1.5 x 10(-2) at pH 11.5. Forced photodegradation of labetalol solutions under exposure to UVA--UVB radiations (xenon arc lamp) was monitored by reversed-phase liquid chromatography. The main photodegradation products were isolated and characterized by NMR and mass spectrometry; labetalol was found to give 3-amino-1-phenylbutane and salicylamide-4-carboxaldehyde as the main photoproducts. Preliminary phototoxic testings on human keratinocyte cultures were performed evaluating the viability of the cells by the neutral-red uptake assay; mutagenic and photomutagenicity tests were also carried out based on Salmonella typhimurium strains. As a result, labetalol was found to be photolabile,mainly in alkaline medium, but evidences of significant phototoxic and photomutagenic effects by the drug were not observed.

3T3 Cells↗

Pustular psoriasis of the nails: treatment and long-term follow-up of 46 patients.

BACKGROUND: Pustular psoriasis of the nail apparatus is a common disease that greatly influences the quality of life because of its chronic course and poor response to treatment. OBJECTIVES: To review the clinical and histopathological features, the response to treatment and the long-term follow-up of 46 patients with pustular psoriasis of the nail unit. METHODS: Treatments utilized included oral retinoids (n = 12), oral nimesulide (n = 13), topical calcipotriol (n = 15) and topical steroids (n = 18). Retinoids were utilized as first choice in seven patients with involvement of several digits and in five patients with severe relapses, whereas topical calcipotriol, oral nimesulide or topical steroids were utilized in patients with involvement of a single nail. Topical calcipotriol was also prescribed as maintenance therapy in patients who responded to oral treatment. Twenty-five patients were followed for more than 5 years. RESULTS: Improvement or regression of the lesions was obtained in 23 of 46 patients. Retinoids were effective in six of 12 patients, nimesulide in four of 13, topical calcipotriol in nine of 15 and topical steroids in four of 18. The long-term follow-up showed a complete remission of the disease in only two patients, both affected by pustular psoriasis involving multiple nails. All other patients experienced periodic relapses which were in most cases controlled by regular use of topical calcipotriol. CONCLUSIONS: Severe cases of pustular psoriasis of the nail are best treated with systemic retinoids. Topical calcipotriol is effective in about 50% of patients with localized disorder and is also useful as maintenance therapy after retinoid treatment.

Adolescent↗

Evaluation of sexual function in subjects taking finasteride for the treatment of androgenetic alopecia.

BACKGROUND: Our practical experience indicates that sexual side-effects in subjects taking finasteride 1 mg (Propecia) for androgenetic alopecia are much less common than reported in the literature. OBJECTIVE: To evaluate the sexual function in subjects taking finasteride (1 mg) compared with age-matched controls using the International Index of Erectile Function (IIEF). METHODS: The IIEF, a brief, reliable questionnaire, was self-administered to 236 patients taking Propecia and 236 age-matched males attending the Department of Dermatology of the University of Bologna. RESULTS: Statistical analysis showed no differences between scores obtained with the IIEF in subjects taking finasteride and controls. CONCLUSIONS: The sexual and erectile function of subjects taking finasteride does not significantly differ from that of age-matched controls. This is consistent with the experience of many dermatologists who do not see sexual or erectile dysfunction in patients taking Propecia.

Adolescent↗

Distal digital keratoacanthoma: two cases with a review of the literature.

BACKGROUND: Distal digital keratoacanthoma (DKA) is an uncommon tumor difficult to diagnose clinically, and even histologically, with certainty. OBJECTIVE: Our purpose is to report on two new cases and to discuss the clinical, histologic, and differential diagnosis. METHODS: We have reviewed all well documented cases published in the literature. RESULTS: No single diagnostic criterion is sufficiently sensitive and specific to be pathognomonic. CONCLUSION: The diagnosis of DKA should be based on the correlation of clinical, radiological and pathologic findings, but the tumor is frequently diagnosed histologically as "squamous cell carcinoma, keratoacanthoma type" or as keratocarcinoma.

Adult↗

Telogen effluvium after allergic contact dermatitis of the scalp.

OBJECTIVE: After observing 2 cases of acute telogen effluvium induced by allergic contact dermatitis to hair dyes, we decided to evaluate the effects of acute contact dermatitis of the scalp on the hair cycle. DESIGN: Single-center, 6-month study of consecutive patients affected by acute scalp dermatitis. SETTING: Department of Dermatology, University of Bologna, Bologna, Italy. PATIENTS: Diagnosis of allergic contact dermatitis of the scalp was confirmed by patch testing. Eight women presenting with acute contact dermatitis of the scalp entered the study. Hair shedding was evaluated monthly for 6 months by pull test and wash test. Increased hair loss was detected in 4 of the 7 patients who completed the study. Hair loss was mild to moderate and appeared 2 to 4 months after the episode of scalp dermatitis. A scalp biopsy specimen from 2 patients confirmed the diagnosis of telogen effluvium. CONCLUSIONS: Allergic contact dermatitis of the scalp should be included among the possible causes of telogen effluvium. The pathogenesis of telogen effluvium caused by contact dermatitis is unknown but may be related to cytokine release during the inflammatory process.

Acute Disease↗

Warts of the nail unit: surgical and nonsurgical approaches.

BACKGROUND: Warts are the most common nail tumor and mostly affect children and young adults. Periungual warts are usually due to HPV-1, 2, and 4. Development of periungual warts is favored by maceration and trauma, especially nail biting. OBJECTIVE: To discuss the biology, clinical features, and medical and surgical treatment of periungual warts. METHODS: Review of the literature and personal experience. RESULTS: The natural course of warts makes aggressive approaches restricted to selected cases. Medical treatments, usually topical, include keratolytic agents, virucidal agents, and immunomodulators. All choices have been utilized successfully, but keratolytic agents are the best first-line approach. Surgical treatments include cryotherapy, surgical excision, electrosurgery, infrared coagulation, localized heating with a radio-frequency heat generator and laser therapy, especially the Er:YAG laser, which has an excellent safety profile. CONCLUSIONS: Definitive cure is not guaranteed by any therapy and periungual warts can recur and become larger after correct treatment.

Diagnosis, Differential↗

Hair diameter diversity: a clinical sign reflecting the follicle miniaturization.

BACKGROUND: The degree of androgenetic alopecia is generally evaluated either by global clinical scales or time-consuming methods like phototrichogram or histological studies. We describe a new clinical and reliable scoring method based on hair diameter diversity. OBSERVATIONS: (1) The clinical macroscopic scoring we propose for hair density was significantly correlated with Hamilton classification and with histological hair density. (2) Diversity in hair diameter was the main and most accurate clinical parameter linked to follicle miniaturization. (C) The anagen-telogen ratio decreased in parallel with the decrease in clinical hair density score. CONCLUSIONS: Considering that hair follicle miniaturization is the key point during androgenic alopecia onset and development, diversity in hair diameter represents an important feature to consider as an accurate clinical sign reflecting hair follicle miniaturization. Moreover, diversity in hair diameter seems to be an easily accessible and reliable parameter that should be taken into consideration for further characterization of hair disorders. By itself, we believe that this clinical feature constitutes a new tool of substantial help for the diagnosis and management of androgenic alopecia.

Adult↗

Nail lichen planus in children: clinical features, response to treatment, and long-term follow-up.

OBJECTIVE: To report clinical features, response to treatment, and long-term follow-up of nail lichen planus in children. DESIGN: Retrospective study involving 15 children with nail lichen planus. SETTING: Outpatient consultation for nail disorders at the Department of Dermatology of the University of Bologna, Bologna, Italy. PATIENTS OR OTHER PARTICIPANTS: We diagnosed nail lichen planus in 15 children younger than 12 years, including 10 children with typical nail matrix lesions, 2 children with 20-nail dystrophy (trachyonychia), and 3 children with idiopathic atrophy of the nails. Only 2 of the 15 children had oral lichen planus; none had cutaneous lesions. A nail biopsy confirmed the diagnosis in all cases. INTERVENTION: Intramuscular triamcinolone acetonide, 0.5 to 1 mg/kg per month, was prescribed to children with typical nail lichen planus and prolonged from 3 to 6 months until the proximal half of the nail was normal. No treatment was prescribed to patients with 20-nail dystrophy or idiopathic atrophy of the nails. RESULTS: Treatment with systemic corticosteroids was effective in curing typical nail lichen planus. Two children experienced a recurrence of the disease during the follow-up. Recurrences were always responsive to therapy. The 2 children with 20-nail dystrophy improved without any therapy. Nail lesions caused by idiopathic atrophy of the nails remained unchanged during the follow-up period. CONCLUSIONS: Nail lichen planus in children is not rare but probably underestimated. It often presents with atypical clinical features such as 20-nail dystrophy or idiopathic atrophy of the nails.

Child↗

Onychomycosis caused by nondermatophytic molds: clinical features and response to treatment of 59 cases.

BACKGROUND: Nail invasion by nondermatophytic molds (NDM) is considered uncommon with prevalence rates ranging from 1.45% to 17. 6%. OBJECTIVE: We report the clinical features and response to treatment of onychomycosis caused by these molds. METHODS: From 1995 through 1998 we performed a mycologic study on 1548 patients affected by nail disorders, and we diagnosed 431 cases of onychomycosis including 59 cases of onychomycosis caused by molds. These include 17 patients with onychomycosis caused by Scopulariopsis brevicaulis, 26 patients with onychomycosis caused by Fusarium sp, 9 patients with onychomycosis caused by Acremonium sp, and 7 patients with onychomycosis caused by Aspergillus sp. RESULTS: Onychomycosis caused by S brevicaulis, Fusarium sp, and Aspergillus sp may often be suspected by clinical examination. In fact 38 of 50 patients with onychomycosis resulting from these molds were affected by proximal subungual onychomycosis associated with inflammation of the proximal nailfold. In our experience mold onychomycosis is not significantly associated with systemic diseases or immunodepression. NDM are difficult to eradicate; by using and combining different treatments (systemic itraconazole, systemic terbinafine, topical terbinafine after nail plate avulsion, and ciclopirox nail lacquer) we were able to cure only 69.2% of patients with S brevicaulis onychomycosis, 71.4% of patients with Acremonium onychomycosis, and 40% of patients with Fusarium onychomycosis. Aspergillus onychomycosis, on the other hand, responded very well to therapy and all our patients were cured after systemic or topical treatment. Eradication of the mold produced a complete cure of the nail abnormalities in all the patients who responded to treatment. CONCLUSION: Clinical examination usually suggests diagnosis of onychomycosis resulting from NDM. Topical treatment can be more successful than systemic therapy to cure onychomycosis caused by S brevicaulis, Fusarium sp, and Acremonium sp.

Administration, Topical↗

Treatment of common nail disorders.

Treatment of nail diseases is not always easy; topical treatment is often ineffective because the nail plate is not penetrated by topical drugs, and the nail matrix is located under the proximal nail fold. The most frequent nail disorders are nail psoriasis and onychomycosis. In these cases, systemic treatment is often necessary to cure the nail changes. Systemic treatment with steroids is mandatory for patients with nail lichen planus because the disease may cause definitive destruction of the nail matrix. Environmental nail abnormalities are frequent and include nail brittleness, onycholysis, and chronic paronychia. Preventive measures should always be associated with treatment in these cases.

Humans↗

Patch testing with corticosteroid mixes in Europe. A multicentre study of the EECDRG.

This study investigated whether a corticosteroid mix containing tixocortol pivalate, budesonide, and hydrocortisone-17-butyrate could detect contact allergy to corticosteroids. 2 corticosteroid mixes, 1 with a high (mix I) and 1 with a low (mix II) concentration and the 3 individual constituents, each at 2 concentrations, were inserted into the standard series of 16 participating clinics. Tests were read on day (D) 3 or 4. 5432 patients were tested, and 110 (2.0%) had positive reactions to at least 1 of the 8 test preparations. Of the 8 preparations, mix I identified most allergic patients, followed by mix II, budesonide 0.10%, budesonide 0.002%, and tixocortol pivalate, both concentrations (1.0 and 0.10%) tracing the same number. With the mixes, 53.2-59.6% of tixocortol pivalate allergy was missed. 47 patients were allergic to either concentration of tixocortol pivalate, 25% of these only to 1.0% and another 25% only to 0.10%. Testing with mix I and tixocortol pivalate 0.10% picked up 98/110, testing with tixocortol pivalate 1.0% and 0.10% and budesonide 0.10% picked up 105/110. 3379 patients were read on both D3 or D4 as well as on D7. Without a late reading (D7), up to 30% of contact allergy to corticosteroid markers was missed.

Administration, Topical↗

Provocative use testing of methyldibromo glutaronitrile in a cosmetic shampoo.

Methyldibromo glutaronitrile (1,2-dibromo-2,4-dicyanobutane, MDGN) is a component of Euxyl K400, a broad-spectrum preservative increasingly used in cosmetics over the last 10 years. Contact allergy to MDGN is not uncommon, with leave-on cosmetics and moistened toilet tissue being the most important sources. Rinse-off products have rarely been reported to elicit allergic reactions in patients sensitized to MDGN and shampoos have only been implicated in hairdressers. To determine whether subjects sensitized to MDGN would react in a provocative use test with a shampoo containing the preservative, we asked 12 pre-sensitized subjects to use a shampoo containing 0.02% MDGN for a period of 9-13 weeks. During this time, none of the subjects showed any skin reactions indicative of contact allergy. The results of this study provide evidence to support that a shampoo product containing 0.02% MDGN may safely be used by most individuals who are presensitized to MDGN.

Adolescent↗