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Biomedical subjects

A Locatelli

Publications and source records attributed to A Locatelli.

At least 19 recordsLinked to original sources
PubMed2006

Formation of regular surface-supported mesostructures with periodicity controlled by chemical reaction rate.

We report a LEEM and XPEEM study of the formation of a variety of stationary two-dimensional metallic and oxygen structures in Au and Au + Pd adlayers on Rh(110) during water formation reaction. They result from chemically frozen spinodal decomposition and are created, preserved, or reversibly modified by tuning the reaction conditions. The wavelength of lamellar structures obtained at intermediate metal coverage is found to obey a power scaling law with respect to the reaction rate.

Letter↗
PubMed2006

Diffusion dynamics during the nucleation and growth of Ge/Si nanostructures on Si(111).

We report a low energy electron microscopy study of the relation between self-organized Ge/Si(111)nanostructures and their local environment. By comparison with Monte Carlo simulations, three-dimensional islands are shown to display a substantial tendency towards self-ordering. This tendency may result from the diffusive nature of the nucleation processes. The size of individual nanostructures does not significantly correlate with the distance between neighboring islands. Thus energetic factors are thought to govern the competition among coexisting nanostructures to capture the deposited mass.

Journal Article↗
PubMed2005

Imaging of ferroelectric thin films by X-ray photoemission electron microscopy (XPEEM).

We performed X-ray photoemission electron microscopy (XPEEM) measurements at the Nanospectroscopy Beamline of the synchrotron light source ELETTRA, Trieste, Italy, to demonstrate the principal possibility of imaging ferroelectric thin films by low-energy photoelectrons. Due to the insulating properties of ferroelectric films, severe surface charging was the major experimental challenge to overcome. This was achieved by grounding an array of gold inter-digital electrodes (with 5 microm blank intervals between them) deposited on top of the films. The images taken with BaTiO(3) films revealed 50-100 nm-sized holes (material discontinuities) on the surface, an observation confirmed by high-resolution scanning electron microscopy (HRSEM). Finer details, e.g. a granular structure, which has been resolved with HRSEM, could not be observed in the XPEEM images. Our measurements indicate that despite some residual charging, a 50 nm lateral resolution can be achieved in XPEEM measurements with ferroelectric films.

Journal Article↗
PubMed2004

Tuning surface reactivity via electron quantum confinement.

The effect of electron quantum confinement on the surface reactivity of ultrathin metal films is explored by comparing the initial oxidation rate of atomically flat magnesium films of different thickness, using complementary microscopy techniques. Pronounced thickness-dependent variations in the oxidation rate are observed for well ordered films of up to 15 atomic layers. Quantitative comparison reveals direct correlation between the surface reactivity and the periodic changes in the density of electronic states induced by quantum-well states crossing the Fermi level.

Journal Article↗
PubMed2004

Phase IB and pharmacological study of the novel taxane BMS-184476 in combination with doxorubicin.

The aim of this study was to define the maximum tolerated dose (MTD) and the pharmacological profile of the paclitaxel analogue BMS-184476 given once every 3 weeks, or on days 1 and 8 every 3 weeks (d1&8), in combination with a fixed dose of 50 mg/m(2) of Doxorubicin (Doxo) administered on day 1 of a 21-day cycle. Adult patients with advanced solid malignancies received escalating doses of BMS-184476 infused over 1 h after bolus Doxo. Pharmacokinetics (PK) of BMS-184476, Doxo and metabolites were investigated. The effect of BMS-184476 on doxorubicinol formation was studied in the cytosol from human myocardium. The MTD of 3-weekly BMS-184476 was 30 mg/m(2). The MTD/recommended Phase II dose was 35 mg/m(2)/week (70 mg/m(2) per cycle) in the d1&8 schedule. The dose-limiting toxicity was neutropenia for both schedules. Other toxicities were loss of appetite, asthenia, and mild, cumulative peripheral neuropathy. The objective response rate in 17 previously untreated or minimally pretreated patients with breast cancer treated at 35 mg/m(2)/week of BMS-184476 was 59% (95% Confidence Interval (CI): 33-82%). Two of the 7 patients not responding to the study regimen later responded to Doxo and paclitaxel. Plasma disposition of BMS-184476 at 30, 35 and 40 mg/m(2) was linear without evidence of a PK interaction with Doxo. In studies with cytosol from human myocardium, the formation of cardiotoxic doxorubicinol was not enhanced by BMS-184476. Dosing of BMS-184476 for 2 consecutive weeks allowed the administration of larger doses of the taxane with a promising antitumour activity in patients with untreated or minimally pretreated breast cancer. The higher than expected myelotoxicity of the 3-weekly schedule is unexplained by the investigated interactions. Lack of enhanced doxorubicinol formation in human myocardium is consistent with the cardiac safety of the regimen.

Aged↗
PubMed2004

Serial assessment of amniotic fluid index in uncomplicated term pregnancies: prognostic value of amniotic fluid reduction.

OBJECTIVE: Assessment of amniotic fluid volume in association with a non-stress test is a commonly used method to monitor fetal well-being in high-risk pregnancies. The aims of our study were to determine whether oligohydramnios and the trend in amniotic fluid volume have prognostic significance in low-risk pregnancies between 40.0 and 41.6 weeks' gestation. METHODS: Between January 1997 and December 2000, all uncomplicated gestations with a singleton non-anomalous fetus reaching 40.0 weeks' gestation underwent semi-weekly monitoring of amniotic fluid index (AFI) until delivery. Oligohydramnios was defined as an AFI of < or = 5 cm. Changes in AFI were expressed as centimeters per day, and were calculated as: [(last AFI before delivery minus first AFI at 40.0 weeks) / interval in days between the two scans]. Adverse outcome was considered the occurrence of 5-min Apgar score < 7; umbilical artery pH < 7.0; Cesarean section for fetal distress; or fetal death. Comparisons between the groups with favorable and adverse outcomes was performed with chi(2) or Fisher's exact test for categorical variables, and Student's t test for continuous variables. A two-tailed p value < 0.05 was considered significant. RESULTS: A total of 3050 women met the study criteria, and underwent a median number of two (range 1-7) sonographic assessments of AFI after 40.0 weeks, with oligohydramnios detected in 341 women. In 1466 women at least two serial AFI determinations were obtained, allowing computation of an AFI trend. Gestations resulting in adverse perinatal outcome (n = 167, 5.5%) had a significantly higher rate of oligohydramnios (33/167, 19.8% vs. 308/2883, 10.7%, p = 0.001), but a similar rate of reduction in AFI ( -0.65 +/- 0.64 vs. - 0.66 +/- 0.66 cm/day; p = 0.85) than those with favorable outcome. The difference in rate of reduction of AFI between the two groups was not significant, even in the subset of gestations that developed oligohydramnios ( -1.08 +/- 0.87 vs. -1.26 +/- 0.89 cm/day; p = 0.27). CONCLUSION: A sonographic diagnosis of oligohydramnios carries an increased risk of adverse perinatal outcome, even in low-risk pregnancies after 40 weeks. The trend in amniotic fluid volume reduction does not seem to have prognostic significance.

Adult↗
PubMed2004

5% Imiquimod cream for external anogenital warts in HIV-infected patients under HAART therapy.

The efficacy of imiquimod in the treatment of external genital warts in HIV positive subjects was compared to a group of patients with normal immune function. Imiquimod 5% cream was applied by patients three times a week until resolution for a maximum of 16 weeks. Assessment for response and the occurrence of side effects was performed every four weeks. Thirty-one per cent of 75 HIV positive patients achieved a complete clearance, a partial response was obtained in 24% of subjects while in 45% we observed no clinical response. In the control group a total clearance was obtained in 62% of subjects, a partial response in 24% and no response in 14%. Recurrences occurred in 4/23 HIV patients and 2/31 immunocompetent patients within three months of follow-up. Side effects were minor to moderate. We conclude that imiquimod 5% cream has an acceptable efficacy and safety on HIV patients.

Administration, Cutaneous↗
PubMed2002

Pathology findings in preterm placentas of women with autoantibodies: a case-control study.

OBJECTIVE: To evaluate the placental histopathology findings in women with systemic lupus erythematosus or antiphospholipid syndrome delivered preterm. METHODS: We performed a case-control study comparing clinical outcomes and placental histopathology of 18 consecutive singleton pregnancies with systemic lupus erythematosus (n = 9) or antiphospholipid syndrome (n = 9) delivered between 24 and 37 weeks, and 54 controls matched for gestational age and type of preterm delivery (spontaneous or indicated). Placental examinations were performed by a single pathologist, and placental lesions were grouped into four categories: uteroplacental vascular pathology and related villous lesions; coagulation-related damage; chronic inflammation; and acute inflammatory lesions. Statistical analysis included the Mantel-Haenzsel or Fisher's exact test, and logistic regression, with a value of p < 0.05 or an odds ratio (OR) with 95% confidence intervals (Cl) not inclusive of unity considered significant. RESULTS: Lupus anticoagulant was positive in ten out of 18 cases and medium or high positive IgG anticardiolipin antibodies in seven out of 18. Antenatal treatment included corticosteroids (n = 9), low-dose aspirin (n = 15) and heparin (n = 8). Rates of necrotizing enterocolitis (33% vs. 0%, p < 0.001) and of perinatal mortality (33% vs. 9%, p = 0.02) were significantly different between cases and controls, and rates of birth weight < 10th centile approached statistical significance. Uteroplacental vascular lesions (OR 3.7, 95% CI 1.1, 11.7) and coagulation-related damage (OR 16.8, 95% CI 3.9, 72.6) were significantly more common among cases than controls, and rates of chronic inflammatory lesions approached significance. CONCLUSIONS: Cases of systemic lupus erythematosus and antiphospholipid syndrome delivered preterm are associated with a significant increase in placental vascular and coagulation-related lesions, which are reflected clinically by higher rates of perinatal mortality, necrotizing enterocolitis, and small-for-gestational age neonates.

Adult↗
PubMed2001

Synthesis and screening for antiacetylcholinesterase activity of (1-benzyl-4-oxopiperidin-3-ylidene)methylindoles and -pyrroles related to donepezil.

The design, synthesis, and rapid evaluation of a new class of acetylcholinesterase (AChE) inhibitors related to donepezil are reported. A molecular dynamics simulation of the complex between AChE and one representative compound of the series showed a possible inhibitor binding mode in which favorable interactions are formed between the benzylpiperidinone moiety and some active-site residues. The biochemical evaluation of this newly synthesized series was performed using a chemiluminescent method suitable for high-throughput screening.

Acetylcholinesterase↗
PubMed2001

Clinical and pharmacologic study of the epirubicin and paclitaxel combination in women with metastatic breast cancer.

PURPOSE: A pharmacokinetic interaction may cause increased cardiotoxicity of paclitaxel (PTX) and high cumulative dose of doxorubicin. We tested antitumor activity, tolerability, and pharmacokinetics of the lesser cardiotoxic epirubicin (EPI) and PTX (ET combination). PATIENTS AND METHODS: Twenty-seven women with untreated metastatic breast cancer, median age of 56 years, and prominent visceral involvement (74%) were studied. Three-weekly EPI (90 mg/m(2)) and PTX (200 mg/m(2) over 3 hours) were given for a maximum nine cycles. EPI was administered 24 hours before PTX (E --> T) in cycle 1, and 15 minutes before PTX (ET) thereafter. EPI, epirubicinol (EOL), EPI-glucuronide (EPI-glu), EOL-glucuronide (EOL-glu), PTX, and 6alpha-OH-PTX were measured in plasma and urine in 14 women. RESULTS: Patients received 205 cycles of ET and a median EPI dose of 720 mg/m(2). Grade 4 neutropenia (49% of cycles) was the most frequent toxicity. Cardiac contractility was decreased in five patients. Mild congestive heart failure occurred in two (7.4%). Response rate was 76% (28% complete). Median overall survival was 29 months. On the basis of intrapatient comparison in the first 24 hours of E --> T and ET cycles, PTX did not affect EPI disposition, but significantly increased plasma exposure to EOL (by 137%), EPI-glu (threefold) and EOL-glu (twofold). Urinary excretion of EPI dose went from 8.2% in E --> T to 11.8% in ET cycles. Clearance of PTX was 30% slower in ET than E --> T. ET cycles caused lower neutrophil nadir than E --> T (644 +/- 327 v 195 +/- 91, P <.05) CONCLUSION: ET is feasible, devoid of excessive cardiac toxicity, and active. A reciprocal pharmacokinetic interference between the two drugs has pharmacodynamic consequences, and suggests a direct effect of PTX on EPI metabolism requiring ad hoc investigation.

Adult↗
PubMed2001

Survival and reproductive function after treatment of malignant germ cell ovarian tumors.

PURPOSE: Germ cell ovarian tumors are curable. The possible sequelae of chemotherapy on long-term survivors are still unknown, but these patients may expect normal lives. The aim of this study was to evaluate the outcome and reproductive function in a population of women treated since 1982. MATERIALS AND METHODS: Between 1982 and 1996, 169 women with malignant germ cell ovarian tumors were seen (70 dysgerminomas, 28 endodermal sinus tumors, 24 mixed tumors, and 47 immature teratomas). Seventy-one had advanced or recurrent disease. Fertility-sparing surgery was performed in 138 (81%) women, 81 of whom received postoperative chemotherapy. RESULTS: With a median follow-up of 67 months, the survival rate was 94% for dysgerminoma, 89% for endodermal sinus tumors, 100% for mixed types, and 98% for immature teratoma. For women who were treated conservatively, the survival rate was 98%, 90%, 100%, and 100%, respectively. Two women had adnexal recurrences, and both received salvage treatment. After treatment, all but one postpubertal woman had recovery of menses within 9 months. During follow-up, 12 untreated and 20 treated patients had 55 conceptions. We recorded 40 pregnancies at term, six terminations, and nine miscarriages. Four malformations were observed: one in 14 conceptions of patients who had not received chemotherapy and three in 41 conceptions of treated patients. CONCLUSION: Irrespective of subtype and stage, conservative surgery should become the standard approach to treating most patients with malignant ovarian germ cell tumors. Fertility seems to be only marginally affected by treatments. Miscarriages are in the expected range for the general population. The malformation rate is slightly higher than in the general population, but no significant difference was seen between patients who did and did not receive chemotherapy.

Adolescent↗
PubMed2001

Time course of female-to-male sex reversal in 38,XX fetal and postnatal pigs.

In an attempt to understand the etiology of intersexuality in pigs, we thoroughly analyzed the gonads of 38,XX (SRY negative) female to male sex-reversed animals at different developmental stages: during fetal life [50 and 70 days postcoitum (dpc)], just after birth [35 days postpartum (dpp)] and during adulthood. For each animal studied, we performed parallel histological and ultrastructural analyses on one gonad and RT-PCR analysis on the other gonad in order to define the expression profiles of sexually regulated genes: SOX9, 3beta-HSD, P450 aromatase, AMH, FOXL2, and Wnt4. Light and electron microscopic examination showed that testicular cords differentiated in XX sex-reversed gonads but were hypoplastic. Although the testicular cords contained gonia at the fetal stages, the germ cells had all died through apoptosis within a few weeks after birth. Ultrastructurally normal Leydig cells also differentiated, but later, and enclosed whorl-like residual bodies. At the fetal stages, three of the six genes studied in the intersex gonads presented, as early as 50 dpc, a modified expression profile corresponding to an elevated expression of SOX9 and the beginning of AMH and P450 aromatase gene transcription. In addition to genes involved in the testicular pathway, the same gonads expressed FOXL2, an ovarian-specific factor. The ovaries of true hermaphrodites were ineffective in ensuring correct folliculogenesis and presented abnormal expression profiles of ovarian specific genes after birth. These results indicate that the genes involved in this pathology act very early during gonadogenesis and affect the ovary-differentiating pathway with variable expressivity from ovarian germ cell depletion through to trans-differentiation into testicular structures.

Animals↗
PubMed2001

Synthesis and antitubercular activity of imidazo[2,1-b]thiazoles.

A number of selected imidazo[2,1-b]thiazoles entered the screening at the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) and one of these compounds, 2-chloro-6-phenylimidazo[2,1-b]thiazole, showed antitubercular activity. On this basis we planned the synthesis of new analogues bearing a substituted ring at the 6 position. For one compound only (2-chloro-6-p-chlorophenylimidazo[2,1-b]thiazole) the 5-nitroso derivative was also prepared. The antitubercular activity of these compounds was compared with the known analogues lacking the chlorine at the 2 position. 5-Nitroso-6-p-chlorophenylimidazo[2,1-b]thiazole showed potent antitubercular activity.

Antitubercular Agents↗
PubMed2001

Drug interactions of paclitaxel and docetaxel and their relevance for the design of combination therapy.

The taxanes' interaction with other anticancer drugs have been extensively investigated in in vitro and in animal models as well as in humans due to the outstanding antitumor activity in a broad range of malignancies. Paclitaxel and docetaxel are endowed of a rich and complex pharmacology whereby different pharmacodynamic effects are observed depending on the sequence of their administration in respect with the companion drug, and the type of drug that is combined. Pharmacokinetic interference is often but not always a basis of the pharmacodynamic effect. In addition, the vehicle of clinical formulation, especially Cremophor EL for paclitaxel, influence the pharmacological effect. Finally, new interaction based on as yet unknown mechanisms drive the two taxanes to multiple additive/synergistic relationships with new signal transduction drugs, such as modulators of the epidermal-growth-factor family of receptors and farnesyl-transferase inhibitors. The ongoing effort to better understanding such a rich pharmacology is worth continuing in view of designing new and better combinations of the taxanes.

Animals↗
PubMed2001

Can a cyclo-oxygenase type-2 selective tocolytic agent avoid the fetal side effects of indomethacin?

We evaluated the efficacy and safety of nimesulide (100 mg orally twice daily for > 48 hours) in a pilot series of five women (two with twin pregnancies) at 24(+6) weeks (range 21(+3) - 27(+2)) in preterm labour which was unresponsive to intravenous ritodrine. Nimesulide therapy was continued for eight days (5-16) and was associated with a prolongation of pregnancy of 27 days (6-69). Oligohydramnios occurred in all seven fetuses after three to nine days of therapy, and in the five pregnancies that continued after discontinuation of nimesulide, it resolved within four days (2-7). None of the babies manifested permanent renal damage.

Administration, Oral↗
PubMed2001

Clear cell papulosis (pagetoid papulosis) in a non-Asian patient.

Clear cell papulosis is a recently described disorder which is characterized by multiple flat, slightly elevated, hypopigmented papules, distributed mainly on the lower part of the trunk of healthy children. Histologically, the disease shows 'clear cells' with a pagetoid appearance spread among keratinocytes in basal and suprabasal layers of the epidermis. These cells stain for AE1, CEA and EMA, making a relationship to eccrine or apocrine elements likely. All cases reported until now describe Asian children. The first European child with clear cell papulosis is presented.

Child, Preschool↗
PubMed2000

Piglets born after vitrification of embryos using the open pulled straw method.

Morulae and unhatched blastocysts from Large White hyperprolific (LWh) and Meishan (MS) gilts were selected to test an ultrarapid open pulled straw (OPS) vitrification method with two media. The viability of vitrified/warmed embryos was estimated by the percentage of embryos that developed to the hatched blastocyst stage in vitro or by birth after transfer. In Experiment 1, two cryoprotectant dilution media were compared for cryopreservation of MS and LWh blastocysts: TCM was a standard Hepes-buffered TCM199 + 20% NBCS medium and PBS was a PBS + 20% NBCS medium. After a two-step equilibration in ethylene glycol, dimethyl sulfoxide, and sucrose, 2-5 blastocysts were loaded into OPS and plunged into liquid nitrogen. Embryos were warmed; a four-step dilution with decreasing concentrations of sucrose was applied. In PBS, LWh blastocysts (27%) had a lower viability in vitro than MS blastocysts (67%; P = 0.001). In TCM, no significant difference was observed between genotypes (41% for LWh and 43% for MS blastocysts) and both viability rates were lower than that of the control groups. In Experiment 2, morula-stage LWh and MS embryos were vitrified and warmed using PBS. The viability rate was low and did not differ between LWh (11%) and MS (14%). In Experiment 3, 200 MS and 200 LWh blastocysts were vitrified/warmed as described in Experiment 1 (PBS). In each of 20 MS recipients, 20 embryos were transferred. The farrowing rate was 55% and recipients farrowed four and five piglets (median) for MS and LWh blastocysts, respectively. The OPS method is therefore appropriate for cryopreservation of unhatched porcine blastocysts.

Animals↗