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Biomedical subjects

R Capizzi

Publications and source records attributed to R Capizzi.

At least 19 recordsLinked to original sources

Association between cutaneous melanoma, Breslow thickness and vitamin D receptor BsmI polymorphism.

BACKGROUND: Literature data report an association between some vitamin D receptor (VDR) polymorphisms and different kinds of tumours, including malignant melanoma (MM). Only three VDR polymorphisms (FokI, TaqI and A-1012G) have been investigated in association with the presence of cutaneous MM or the development of metastases. OBJECTIVES: The present paper analyses for the first time the association between BsmI polymorphism and MM prevalence together with Breslow thickness. In addition, the FokI single nucleotide polymorphism was also determined. METHODS: One hundred and one patients with MM and 101 healthy donors matched for age and sex were enrolled. Molecular VDR typing was performed by means of restriction fragment length polymorphism analysis. RESULTS: All cases and controls were in Hardy-Weinberg equilibrium for BsmI, FokI and A-1012G. Significant associations were found between the BsmI bb genotype frequency and MM (P = 0.02) along with Breslow thickness (P = 0.001). This same behaviour was not observed for the FokI or A-1012G polymorphisms. Multivariate logistic regression analysis confirmed these significant results after correction for age, gender, skin type and MM localization. CONCLUSIONS: Although the biological meaning of the effects exerted by BsmI polymorphism is still under debate, the statistical association found in the present study suggests that further work should be done to verify this variant as a possible risk marker for MM and its aggressiveness, also considering that the real association may be due to other unknown genes linked to the BsmI b allele.

Adult↗

Cutaneous manifestations in celiac disease.

Celiac disease (CD) is an autoimmune gluten-dependent enteropathy characterized by atrophy of intestinal villi that improves after gluten-free diet (GFD). CD is often associated with extra-intestinal manifestations; among them, several skin diseases are described in CD patients. The present review reports all CD-associated skin manifestations described in the literature and tries to analyze the possible mechanisms involved in this association. The opportunity to evaluate the possible presence of CD in patients affected by skin disorders is discussed.

Celiac Disease↗

Vitiligo associated with other autoimmune diseases: polyglandular autoimmune syndrome types 3B+C and 4.

Vitiligo is a common skin disease characterized by depigmented maculae resulting from a reduction of the number and function of melanocytes. Many studies suggest that vitiligo might be an autoimmune disease. Vitiligo has been frequently described in association with other autoimmune diseases. Among the diseases described in association with vitiligo are the so-called autoimmune polyglandular syndromes (APS). Vitiligo can be present in all types of APS but the most frequent association appears to be in APS-3. APS-3 was defined as the association between autoimmune thyroiditis and another autoimmune disease. Here we report one patient with thyroiditis, vitiligo and autoimmune gastritis (APS-3B+C), one patient with chronic autoimmune thyroiditis, vitiligo and alopecia (APS-3C), and one case of a young patient with type 1 diabetes mellitus and vitiligo (APS-4), according to the newest classification. We stress the importance of a thorough assessment for autoimmune diseases in selected patients with vitiligo.

Adult↗

Atypical multifocal cutaneous leishmaniasis in an immunocompetent patient treated by liposomal amphotericin B.

Multifocal cutaneous leishmaniasis (MCL) is an extremely rare disease in South Europe, and it mainly affects immunosuppressed patients. We report a case of MCL in an immunocompetent patient affected by type II diabetes mellitus that clinically presented with three large ulcers on the legs with a non-linear distribution and several months later with an erythematous-crusty lesion on the left cheek. Diagnosis of leishmaniasis due to Leishmania infantum was formulated by PCR analysis. Given the diffuse and wide lesions, the unresponsiveness to previous local and systemic treatments, a parenteral i.v. therapy with liposomal amphotericin B at a dosage of 3mg/kg/day for 5 days was started and then repeated on the 14th and 21st days, leading to a clear improvement in the clinical picture. The different clinical expression and the evolution of leishmaniasis depend on both the parasite subtype and the host's immunity status. L. infantum manifests with an atypical clinical feature more frequently than other species. The differential diagnosis for multiple ulcers must include several skin diseases, such as cutaneous TBC, bacterial ulcers, traumatic ulcers, deep mycoses, and sarcoidosis. However, an MCL should always be considered in subjects coming from endemic areas. In our case, the multifocality, the size of the lesions and the unresponsiveness to other treatment indicate a short course treatment with liposomal B amphotericin that proved to be a suitable alternative to traditional drugs used in MCL.

Aminoglycosides↗

Skin tolerability and efficacy of combination therapy with hydrogen peroxide stabilized cream and adapalene gel in comparison with benzoyl peroxide cream and adapalene gel in common acne. A randomized, investigator-masked, controlled trial.

BACKGROUND: Combination therapy with antiseptics such as benzoyl peroxide (BP) and topical retinoids is widely used as first-line treatment for acne vulgaris (AV). However, these combinations could have a suboptimal skin tolerability. Recently, a new formulation of hydrogen peroxide (HP) 1% in stabilized cream (Crystacide; Mipharm, Milan, Italy) became available. A previous clinical study has shown that HP cream monotherapy presents a better skin tolerability in comparison with BP in patients with mild AV. OBJECTIVES: To evaluate the tolerability and the efficacy of combination therapy with HP cream and adapalene 0.1% gel in comparison with the combination of BP 4% cream and adapalene 0.1% gel in the treatment of mild to moderate AV. METHODS: In a randomized, investigator-blinded trial, 52 patients (mean +/- SD age 25 +/- 6 years; 19 men and 33 women) with AV were randomly assigned to HP cream and adapalene gel (group HP + A) or to BP cream and adapalene gel (group BP + A), for eight consecutive weeks. Efficacy was assessed by total (TL), inflammatory (IL) and noninflammatory (NL) lesion counts performed at baseline and weeks 4 and 8. Tolerability was assessed by evaluating skin erythema, burning and dryness at weeks 4 and 8. RESULTS: All patients completed the study. At baseline, the mean +/- SD numbers of TL, IL and NL were 44 +/- 9, 25 +/- 7 and 19 +/- 6 in group HP + A and 40 +/- 9, 21 +/- 7 and 19 +/- 9 in group BP + A, respectively. At the end of the treatment period, TL, IL and NL were reduced by 93%, 92% and 95%, respectively, in group HP + A and by 88%, 86% and 90%, respectively, in group BP + A. A significantly (P = 0.0025) greater reduction in NL was observed in group HP + A in comparison with group BP + A. Tolerability was significantly better in group HP + A in comparison with group BP + A (P = 0.02). Skin dryness and burning sensation were more frequent in group BP + A. CONCLUSIONS: The combination of adapalene and HP cream is an effective topical treatment regimen in mild to moderate AV. This combination has shown a better tolerability profile in comparison with the combination of BP and adapalene.

Acne Vulgaris↗

Huriez syndrome: case report with a detailed analysis of skin dendritic cells.

We report a 60-year-old man with familial scleroatrophic syndrome of Huriez who developed squamous cell carcinomas on the affected skin of the right palm. Immunohistochemical analysis showed a marked reduction in the number of CD1a+, Lag+ and S100+ epidermal Langerhans cells, but not of CD1b+ and factor XIIIa+ dermal dendritic cells, limited to palmoplantar skin. The Langerhans cell depletion was not associated with an abnormal skin content of mRNA for factors involved in Langerhans cell development or recruitment in the epidermis, including granulocyte/macrophage colony-stimulating factor, transforming growth factor-beta1 and macrophage inflammatory protein-3alpha. The results indicate that other as yet unknown mechanisms may account for the reduced number of Langerhans cells in the affected skin of such patients.

Carcinoma, Squamous Cell↗

Stimulation of hematopoiesis by amifostine in patients with myelodysplastic syndrome.

The aminothiol, amifostine (Ethyol; U.S. Bioscience, West Conshohocken, PA), is a cytoprotective agent that ameliorates the toxicities of anticancer therapy. In vitro, amifostine promotes the formation and survival of primitive hematopoietic progenitors derived from myelodysplastic bone marrow (BM) specimens. To evaluate the hematological effects of amifostine, 18 patients with myelodysplastic syndrome (MDS) and one or more refractory cytopenias received treatment with amifostine in a Phase I/II study. Four cohorts received intravenous treatment with 100, 200, or 400 mg/m2 amifostine three times a week, or 740 mg/m2 weekly for three consecutive weeks followed by 2 weeks observation. Nonresponding patients received a second course of therapy at the next higher dose level depending upon drug tolerance. Bone marrow (BM) progenitor growth was assessed before treatment and after day 21. Diagnoses included refractory anemia (7), refractory anemia with ringed sideroblasts (5), refractory anemia with excess blasts (RAEB) (4), and RAEB-in transformation (RAEB-t) (2). Single- or multi-lineage hematologic responses occurred in 15 patients (83%) treated with the three-times-a-week dose schedule. Fourteen patients had a 50% or greater increase in absolute neutrophil count with amifostine treatment (range, 426 to 11,348/microL). Platelet count increased in 6 (43%) of 14 patients with thrombocytopenia (absolute increase, 16, 000 to 110,000/microL), and 5 of 15 red blood cell transfusion-dependent patients had a 50% of greater reduction in transfusion needs. Assayable hematopoietic progenitors increased in 13 of 15 evaluable patients; including CFU-GEMM (12), BFU-E (8), and CFU-GM (6). Amifostine doses less than or equal to 200 mg/m2 were well tolerated, whereas grade II nausea, vomiting, and fatigue was limiting at higher doses. Three patients with excess blasts before enrollment experienced an increase in BM blast percentage and two patients had evolution to acute leukemia that persisted after treatment withdrawal. We conclude that amifostine administered at doses </=200 mg/m2 three times a week is well tolerated and has hematologic activity in patients with MDS.

Aged↗

Randomized trial of carboplatin plus amifostine versus carboplatin alone in patients with advanced solid tumors.

BACKGROUND: To test the hypothesis that the cytoprotectant amifostine attenuates the thrombocytopenia produced by carboplatin, the authors performed a randomized trial comparing treatment with carboplatin alone versus the combination of amifostine and carboplatin. METHODS: Patients with refractory or carboplatin-sensitive malignancies were randomized to receive either carboplatin, 500 mg/m2 alone or carboplatin, 500 mg/m2 in conjunction with 2 doses of amifostine of 910 mg/m2 each. RESULTS: Fifty-five patients with a variety of malignancies were entered on this study. One patient withdrew from each arm prior to the administration of any therapy, leaving 30 evaluable patients treated with carboplatin alone and 23 treated with the combination of amifostine and carboplatin. For 82 cycles of therapy with amifostine plus carboplatin, the median platelet nadir was 127 x 10(9)/L while the median platelet nadir was 88 x 10(9)/L over the 80 courses of therapy with carboplatin alone (P = 0.023). The median platelet nadir after the first cycle of therapy was 144 x 10(9)/L for patients treated with amifostine plus carboplatin and 85 x 10(9)/L for patients treated with carboplatin alone (P = 0.24). The median survival for 9 patients with advanced nonsmall cell lung carcinoma treated with carboplatin alone was 39 weeks whereas the median survival for 12 such patients treated with amifostine plus carboplatin was 52 weeks (P = 0.116). CONCLUSIONS: These data support the hypothesis that amifostine attenuates the myelosuppression of carboplatin. Additional studies of amifostine in combination with carboplatin-containing chemotherapy regimens are warranted.

Adult↗

Phase II study of trimetrexate, fluorouracil, and leucovorin for advanced colorectal cancer.

PURPOSE: A phase II study to evaluate the response rate and toxicities of a trimetrexate, fluorouracil (5FU), and leucovorin regimen in patients with advanced incurable colorectal cancer. PATIENTS AND METHODS: Thirty-six patients with unresectable or metastatic colorectal cancer who had not been treated for advanced disease received the following chemotherapy regimen weekly for six courses every 8 weeks: trimetrexate 110 mg/m2 intravenously (I.V.) on day 1, leucovorin 200 mg/m2 I.V. on day 2 (24 hours later), 5FU 500 mg/m2 on day 2 immediately following leucovorin, and oral leucovorin 15 mg every 6 hours for seven doses starting 6 hours after 5FU. Patients were treated until progression or unacceptable toxicity. RESULTS: Thirty patients were assessable for response, and all 36 were assessable for toxicity. Two patients (7%) achieved a complete response (CR) and 13 (43%) a partial response (PR), for an overall response (OR) rate of 50% (95% confidence interval [CI], 32% to 68%). Analysis by intent to treat demonstrated a 42% OR rate (95% CI, 26% to 58%). At final analysis, 16 patients were alive. The median survival duration for the entire cohort was 53.4 weeks. Gastrointestinal toxicity was most common, with 21 patients (58%) having grade 3/4 diarrhea and 12 patients (34%) grade 3/4 nausea. Hematologic toxicity was generally low grade, although two patients died of sepsis. CONCLUSION: The combination of trimetrexate with 5FU and leucovorin is active in metastatic colorectal cancer. Gastrointestinal toxicity with this regimen is most prominent, but is manageable.

Adult↗

Amifostine: the preclinical basis for broad-spectrum selective cytoprotection of normal tissues from cytotoxic therapies.

Administered prior to cytotoxic chemotherapy or radiation, the aminothiol amifostine provides broad-spectrum cytoprotection of various normal tissues without attenuating antitumor response. The basis for the selectivity of action resides in the anabolism of amifostine at the normal tissue site by membrane-bound alkaline phosphatase. Dephosphorylation to the free thiol WR-1065 is followed by rapid uptake into normal tissues by a carrier-mediated facilitated diffusion process. In contrast, uptake into tumor tissues is slow to negligible. Pretreatment with amifostine provides protection of normal tissues from the cytotoxic effects of alkylating agents, organoplatinums, anthracyclines, taxanes, and radiation. Additionally, the mutagenic and carcinogenic effects of these modalities are also attenuated. Preclinical studies show significant protection of marrow progenitor cells that give rise to the red blood cells, white blood cells, and platelets. Protection of kidneys and neural tissues from cisplatin toxicity has been shown, along with protection of the heart, intestinal crypt cells, and pulmonary tissues from chemotherapy and radiation, as well as vasculoconnective and musculoconnective tissue in an irradiated field. Comparative in vitro and in vivo studies using murine and human tumor xenografts show no attenuation of antitumor effects of these same therapies despite the protection of normal organs. The unique preclinical profile of amifostine serves as the basis for the clinical development program for this important new broad-spectrum cytoprotective agent.

Amifostine↗

Use of amifostine in bone marrow purging.

One of the main obstacles for the use of high-dose chemotherapy with autologous hematopoietic progenitor cell support in the treatment of malignancies is the possibility of reinfusing clonogenic tumor cells with the hematopoietic graft. Purging of the graft with chemicals can reduce the number of tumor cells but can also damage the normal hematopoietic progenitors. Preclinical studies showed that the phosphorylated sulfhydryl compound amifostine (WR-2721) can protect normal hematopoietic progenitors from damage from alkylating agents. We conducted a randomized clinical trial in patients with breast cancer, non-Hodgkin's lymphoma, and Hodgkin's disease undergoing autologous bone marrow transplant. In this study, patients were randomized to have their bone marrow purged with 4-hydroperoxycyclophosphamide (4-HC) with (arm A) or without (arm B) amifostine. The percentage of colony-forming unit granulocyte-macrophages recovered after purging was higher in the amifostine arm, both in patients with breast cancer and in those with lymphoma, although this difference was not statistically significant. In addition, the time to engraftment was significantly shorter in the amifostine arm in both cohorts. We showed that pretreatment of bone marrow with amifostine prior to purging with 4-HC can protect normal hematopoietic progenitors from damage by 4-HC. This resulted in shorter engraftment rates and less need for supportive care.

Adult↗

[Cutaneous tuberculosis: a case of difficult classification].

We describe a case of cutaneous tuberculosis in a 25-year-old Philippine man. Erythematous papulo-nodular lesions, measuring 0.5 to 1 cm, were present on lower limbs; a 2 cm nodule was located on the left flank. The examination of the skin biopsy showed the presence of a superficial and deep perivascular dermatitis with histiocytes, lymphocytes and plasma cells. Ziehl-Nielsen stain for mycobacterium were negative, while the cultural examination led to the isolation of M. tuberculosis. Direct smear and cultural examination of sputum for M. tuberculosis were negative; chest and skeletal roentgenograms, syphilis and HIV infection serology, haematological and hematochemical examinations and urinalysis were negative. Specific treatment with isoniazid, rifampin and ofloxacin led to a rapid remission of cutaneous lesions. This case was particularly difficult to classify, but the Authors think it would be considered a tuberculid.

Adult↗