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Biomedical subjects

M Venturini

Publications and source records attributed to M Venturini.

At least 19 recordsLinked to original sources
PubMed2006

Safety of adjuvant aromatase inhibitor therapy.

The long-term effects of aromatase inhibitors (AIs) on lipids and bone and cardiovascular and gynecological health are of particular interest to clinicians. The safety data of anastrozole, letrozole, and exemestane are limited to trials with follow-up periods of 5 years or less, and much of the data arise from comparisons with tamoxifen, a drug that has both estrogen agonist and antagonist effects. With the lack of extensive long-term data, indirect comparisons between the safety profiles of the AIs provide some insights. Although results from these indirect comparisons should be interpreted cautiously, they may assist physicians in the decision-making process. Thus far, AIs confer an increased risk of bone loss and osteoporosis and fractures, while the effects on lipid profiles and cardiovascular health seem to indicate only that AIs lack the cardioprotective and lipid-lowering effects of tamoxifen. Some data also are available from comparisons with placebo, a more appropriate comparator to investigate the tolerability and safety of a specific drug. In the MA.17 trial, patients receiving letrozole experienced similar rates of cardiovascular ischemic events and hypercholesterolemia compared with those on placebo. The significant clinical benefits of AIs compared with tamoxifen have been achieved without worsening quality of life.

Aromatase Inhibitors↗
PubMed2006

Intercalation of ethidium into triple-strand poly(rA).2poly(rU): a thermodynamic and kinetic study.

The kinetics and equilibria of the interaction of ethidium bromide (EB) with the triple-stranded RNA, poly(rA).2poly(rU), have been investigated by stopped-flow, absorption, fluorescence, and circular dichroism methods; to properly assess the effect of the third strand on the polymer molar properties, molar volumes, adiabatic compressibilities, and heats of melting have also been measured for both poly(rA).2poly(rU) and poly(rA).poly(rU). The melting experiments reveal that ethidium tends to destabilize the triplex, whereas it stabilizes the duplex; however, the triplex/ethidium system in 0.1 M NaCl is stable below 37 degrees C. The static titrations reveal that one ethidium ion binds every three base triplets of the polymer; on the basis of the excluded-site model, this feature suggests intercalation, as in the duplex, but the binding affinity for the triplex is weaker compared to that for the duplex. The kinetic experiments displayed a two-phase behavior, which was rationalized assuming the sequence D + S right arrow over left arrow DS(I), DS(I) + S right arrow over left arrow DS(II) + S (D = drug, S = site), the second step involving direct transfer of the drug between strands. Comparison with the duplex/EB system reveals that the additional strand of poly(U), present in the triplex, hinders the formation of the intermediate complex DS(I), while stabilizing the structure of the final DS(II) complex by hampering the partial slipping out of the dye from the triplex cavity.

Binding Sites↗
PubMed2006

Multicenter phase II study of trastuzumab in combination with epirubicin and docetaxel as first-line treatment for HER2-overexpressing metastatic breast cancer.

The primary objective of study is to evaluate cardiac safety of trastuzumab in combination with epirubicin and docetaxel. HER2-overexpressing metastatic breast cancer patients were enrolled in a two-stage, multicenter phase II trial with weekly trastuzumab (4 and then 2 mg/kg) with epirubicin and docetaxel (either 75 mg/m(2)) on day 1 every 3 weeks. After eight courses of chemotherapy, trastuzumab was continued as a single agent. To assess cardiotoxicity, patients were evaluated for left ventricular ejection fraction (LVEF) at baseline, every two cycles during chemotherapy and trastuzumab, and every 3 months during trastuzumab alone. Cardiotoxicity was defined as signs and/or symptoms of congestive heart failure (CHF) and/or an absolute decrease in LVEF of >or=20 units or a decline to <or=45%. In the first stage of the study, three episodes of cardiotoxicity were observed (two asymptomatic declines of LVEF and one CHF) in 29 patients, and recruitment continued. During follow-up of patients who continued trastuzumab after chemotherapy, seven further cardiologic events occurred (three asymptomatic decline of LVEF and four CHF). Therefore, recruitment was interrupted after the 45th patient. The majority of cardiac events occurred late during trastuzumab alone, half were asymptomatic and all cases of CHF were resolved using cardiac therapy. Complete and partial responses were 20 and 47%, respectively, and the median time to progression was 15.7 months (95% CI, 11.6-19.0 months). In light of the cardiotoxicity experienced during this study, we currently recommend that this combination be used only in controlled clinical trials under vigilant cardiac monitoring.

Adult↗
PubMed2006

Taxane-containing chemotherapy in the treatment of early breast cancer patients.

In primary breast cancer, taxane-based compared with anthracycline-based adjuvant chemotherapy significantly reduces the relative risk of recurrence (ranging from 17% to 36%) and sometimes improves overall survival. Different dosages and schedules of anthracyclines and taxanes have been tested. Randomized studies comparing sequential versus concurrent administrations are in progress and no data about efficacy are available. However, based on a single randomized trial and on indirect comparisons, safety and tolerability seem to be better with sequential schema. A formal comparison between weekly and every 3 weeks administration of taxanes reported no substantial difference in terms of efficacy. However, taking into account a subgroup analysis of this study, and results coming from metastatic disease, the best way to give taxanes seems to be either weekly paclitaxel or docetaxel every 3 weeks. In the majority of the study, taxane efficacy seems to be independent of hormonal receptor status, i.e. active in both hormonal receptor positive and negative disease. In conclusion, taxane-based adjuvant chemotherapy is a standard option for most early breast cancer patients with node-positive disease. No sufficient and dedicated data are available in node-negative disease.

Anthracyclines↗
PubMed2006

Rosemary contact dermatitis and cross-reactivity with other labiate plants.

Rosemary, a plant belonging to the labiate family, is frequently used in the making of cosmetics and also for medicinal purposes. There are few reported cases of contact dermatitis due to this plant. Here we present 1 case and asses the existence of cross-reactivity with plants from the same family. 53-year-old man with several episodes of a pruritic and erythematous eruption that resulted in peeling of the skin, after applying rosemary alcohol, on the chest reported. Epicutaneous tests were done with the standard European series (GEIDC), with the commercial plant series (Bial-Aristegui) and with plants from the labiate family. Results were positive for 3 of 4 labiate species tested. we present a case of rosemary contact dermatitis, where we have found cross-reactivity with 3 of 4 species tested from the same family.

Cross Reactions↗
PubMed2006

Immediate hypersensitivity to corticosteroids.

INTRODUCTION: In comparison with the extremely frequent use of corticosteroids in different diseases, immediate allergic reactions remain uncommon. In addition to the steroid molecule, the causative agent of these reactions can be an excipient. MATERIAL AND METHODS: We report seven cases of immediate reactions induced by different preparations of corticosteroids. Skin tests with the suspected steroid and excipients were carried out. In patients with negative skin tests, oral or parenteral challenges were performed with the drug and the excipients involved. Challenge tests with at least two other corticosteroids belonging to another or even the same group of the Coopman classification were carried out. RESULTS: Of the 7 patients, six had positive skin tests with the suspected preparation of corticoid: three cases with methylprednisolone acetate, two cases with carboxymethylcellulose and one case with the complete triamcinolone preparation. Only in one case did we have to challenge with the suspected steroid preparation to confirm the diagnosis. All challenge tests with other corticosteroids belonging to another or to the same group of the Coopman classification were negative. CONCLUSIONS: The reactions were caused by the steroid molecule (Triamcinolone or methylprednisolone succinate) in four patients, by an excipient (carboxymethylcellulose) in another two patients and we could not identify the sensitized molecule in one patient. We did not demonstrate cross-reactivity between different corticosteroids.

Adrenal Cortex Hormones↗
PubMed2005

Prevention of chemotherapy-induced menopause by temporary ovarian suppression with goserelin in young, early breast cancer patients.

BACKGROUND: Standard methods to prevent chemotherapy-induced early menopause in young, breast cancer patients are unavailable to date. Preclinical data has suggested that luteinising hormone-releasing hormone (LH-RH) analogs given during treatment can decrease the gonado-toxicity induced by chemotherapy. This phase II study aimed to assess the activity of such a method in young, breast cancer patients undergoing adjuvant chemotherapy. PATIENTS AND METHODS: Premenopausal patients received the LH-RH analog goserelin 3.6 mg every 4 weeks before and during chemotherapy. According to two-stage optimal phase II Simon design, treatment was considered clinically interesting if it was able to prevent menopause in 19 out of 29 patients of the study population. The resumption of ovarian function was defined by a resumption of menstrual activity or by a follicle-stimulating hormone (FSH) value < or = 40 IU/l within 12 months after the last cycle of chemotherapy. RESULTS: Thirty patients were enrolled and 29 were evaluable. Median age was 38 years (range 29-47). All but one patient received CEF regimen (cyclophosphamide, epirubicin, 5-fluorouracil). Resumption of menstrual activity was observed in 21 patients (72%; 95% CI 52% to 87%) and a FSH value < or = 40 IU/l in 24 patients (83%; 95% CI 63% to 93%). Menses resumption was observed in 16 out of 17 patients (94%) with age <40 years and in five out of 12 patients (42%) with age > or = 40 years. CONCLUSION: Goserelin given before and during chemotherapy may prevent premature menopause in the majority of patients. The different success rate by age, however, indicates the need of a prospective evidence of the efficacy of such a strategy.

Adult↗
PubMed2005

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↗
PubMed2005

Weekly paclitaxel as first-line chemotherapy in elderly advanced breast cancer patients: a phase II study of the Gruppo Italiano di Oncologia Geriatrica (GIOGer).

BACKGROUND: First-line chemotherapy regimens suitable for elderly advanced breast cancer patients are still not defined. PATIENTS AND METHODS: Women with stage III or IV breast cancer aged > or =70 years were enrolled in a phase II study aimed to evaluate both activity and toxicity of weekly paclitaxel. Among 46 planned patients, at least 18 responses and not more than seven unacceptable toxic events are required for a favourable conclusion. Paclitaxel 80 mg/m(2) was administered weekly for 3 weeks every 28 days. RESULTS: Unacceptable toxicity occurred in seven out of 46 patients evaluated for toxicity [15.2%; exact 95% confidence interval (CI) 7.6% to 28.2%] and was represented by one case of febrile neutropenia, one case of severe allergic reaction and five cases of cardiac toxicity. Among 41 patients evaluated for response, a complete response occurred in two (4.9%) patients and a partial response in 20 (48.8%), with an overall response rate of 53.7% (exact 95% CI 38.7% to 67.9%). The median progression-free survival was 9.7 months (95% CI 8.5-18.7) and median survival was 35.8 months (95% CI 19-not defined). CONCLUSIONS: Weekly paclitaxel is highly active in elderly advanced breast cancer patients. Data on cardiovascular complications, however, indicate the need for a careful monitoring of cardiac function before and during chemotherapy.

Age Factors↗
PubMed2005

Occupational asthma caused by white mushroom.

The commercial growing of white mushroom (Agaricus bisporus) is a frequent activity in certain Spain regions as La Rioja. We report two cases of white mushroom workers suffering from asthma caused by hypersensitivity to basidiocarp and spores of white mushroom.

Adult↗
PubMed2005

Correlation between Chenopodiacea/Amaranthacea pollen counts and allergic symptoms in Salsola kali monosensitized patients.

UNLABELLED: We performed a prospective observational study to establish a relationship between pollen counts of Chenopodiacea/Amaranthacea and clinical symptoms of rhinoconjunctivitis and asthma in a group of monosensitised patients. MATERIAL AND METHODS: A total of 60 patients (19 with asthma) were included in the study. All patients collected daily symptom scores during the summer months of 1999, 2000 and 2001. The questionnaire included ocular, nasal and pulmonary symptoms. Pollen counts were expressed as pollen grains/m3. Symptom scores and pollen counts were correlated using correlation coefficients and Log transformed variables. RESULTS: In the 3 seasons studied we identified a peak of pollen and clinical symptoms in the second half of August and first half of September. In 1999, there was a significant positive correlation between total symptoms and daily pollen grains/m3 (p<0.005, r = 0.347). This correlation was not significant for the summers of 2000 and 2001. After further analysis, and by displacing one of both variables between 11 to 17 days, the correlation coefficients for total symptoms, improved for 1999 (r = 0. 744; p < 0.0001) and became significant for 2000 (r = 0. 521; p < 0.0001) and 2001 (r = 0.635; p < 0.0001). CONCLUSION: We identified a significant time lag between pollen counts and symptom scores in S. kali monosensitized patients.

Adolescent↗
PubMed2004

A model describing stable coherent synchrotron radiation in storage rings.

We present a model describing high power stable broadband coherent synchrotron radiation (CSR) in the terahertz frequency region in an electron storage ring. The model includes distortion of bunch shape from the synchrotron radiation (SR), which enhances higher frequency coherent emission, and limits to stable emission due to an instability excited by the SR wakefield. It gives a quantitative explanation of several features of the recent observations of CSR at the BESSY II storage ring. We also use this model to optimize the performance of a source for stable CSR emission.

Journal Article↗
PubMed2004

Multicenter randomized phase III trial of epirubicin plus paclitaxel vs epirubicin followed by paclitaxel in metastatic breast cancer patients: focus on cardiac safety.

The aim of the study was to evaluate cardiac safety of two different schedules of Epirubicin and Paclitaxel in advanced breast cancer patients enrolled into a multicenter randomized phase III trial. Patients received Epirubicin 90 mg m(-2) plus Paclitaxel 200 mg m(-2) (3-h infusion) on day 1 every 3 weeks for eight courses (arm A), or Epirubicin 120 mg m(-2) on day 1 every 3 weeks for four courses followed by four courses of Paclitaxel 250 mg m(-2) on day 1 every 3 weeks (arm B). Left ventricular ejection fraction was evaluated by bidimesional echocardiography at baseline, after four and eight courses of chemotherapy and every 4 months during follow-up. Baseline median left ventricular ejection fraction was 60% in arm A and 65% in arm B; after four courses, figures were 57 and 60%, respectively. After eight courses, the median left ventricular ejection fraction in arm A declined to 50% while no further reduction was detected in arm B by adding four courses of high-dose Paclitaxel. Seven episodes of congestive heart failure were observed during treatment in arm A. Present monitoring demonstrated that the risk of congestive heart failure or impairment in the cardiac function correlated only with the cumulative dose of Epirubicin; no impact on cardiotoxicity can be attributed to high-dose Paclitaxel.

Adult↗
PubMed2004

Cross-reactivity between obeche wood (Triplochiton scleroxylon) and natural rubber latex.

BACKGROUND: Several studies have shown that allergy to natural rubber latex is associated with cross reactivity to other plants. We have investigated a possible cross reactivity with a tree belonging to the Sterculiaceae family, Tryplochiton scleroxylon, in a patient allergic to obeche wood, that began to suffer symptoms of allergy in contact with latex. METHODS: Determinations of specific IgE by CAP to obeche, natural rubber latex (NRL) and recombinant allergens of latex were done. Immunoblotting was performed to study allergens detected by serum of our patient. CAP-inhibition methods were used to study cross-reactive between NRL and obeche wood. RESULTS: In obeche extract, 4 bands were found of an apparent molecular weight of 18, 38, 75 and 199 kDa. In NRL extract the allergens have a molecular weight around 18, 21, 32, 38, 60, 70 and 199 kDa. IgE to latex was almost completely inhibited (96%) by the obeche extract in CAP-inhibition studies. Using obeche extract as inhibitor, IgE binding to native hevein (nHevb 6.02) was reduced by 25%. CONCLUSIONS: The results obtained in CAP-inhibition demonstrate the existence of cross-reactivity between proteins in NRL and obeche wood. In our patient, a band of apparent molecular weight of 38 kDa could be the most important allergen.

Adult↗
PubMed2004

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↗
PubMed2004

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↗