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Biomedical subjects

R Longo

Publications and source records attributed to R Longo.

At least 19 recordsLinked to original sources

EEG dynamics of the frontoparietal network during reaching preparation in humans.

Visuomotor transformation processes are essential when accurate reaching movements towards a visual target have to be performed. In contrast, those transformations are not needed for similar, but non-visually guided, arm movements. According to previous studies, these transformations are carried out by neuronal populations located in the parietal and frontal cortical areas (the so-called "dorsal visual stream"). However, it is still debated whether these processes are mediated by the sequential and/or parallel activation of the frontoparietal areas. To investigate this issue, we designed a task where the same visual cue could represent either the target of a reaching/pointing movement or the go-signal for a similar but non-targeting arm movement. By subtracting the event-related potentials (ERPs) recorded from healthy subjects performing the two conditions, we identified the brain processes underlying the visuomotor transformations needed for accurate reaching/pointing movements. We then localized the generators by means of cortical current density (CCD) reconstruction and studied their dynamics from visual cue presentation to movement onset. The results showed simultaneous activation of the parietal and frontal areas from 140 to 260 ms. The results are interpreted as neural correlates of two critical phases of visuomotor integration, namely target selection and movement selection. Our findings suggest that the visuomotor transformation processes required for correct reaching/pointing movements do not rely on a purely sequential activation of the frontoparietal areas, but mainly on a parallel information processing system, where feedback circuits play an important role before movement onset.

Adult↗

Rhodotorula mucilaginosa outbreak in neonatal intensive care unit: microbiological features, clinical presentation, and analysis of related variables.

Reported here are the features of a Rhodotorula mucilaginosa outbreak that occurred in a neonatal intensive care unit. Over a period of 19 days, clinical and laboratory signs of sepsis appeared in four premature infants carrying indwelling vascular catheters. After bloodstream infection with R. mucilaginosa was ascertained, the patients underwent amphotericin B therapy and recovered completely. In a retrospective case-control study, the variables displaying a statistical difference between case and control-group neonates were birth weight, gestational age, duration of parenteral nutrition, duration of antibiotic therapy and prophylactic administration of fluconazole. To our knowledge, this is the first reported outbreak caused by yeasts of the Rhodotorula genus.

Amphotericin B↗

Functional MRI in the assessment of cortical activation in subjects with Parkinson's disease.

PURPOSE: The purpose of this study was to evaluate cortical activation patterns in patients with Parkinson's disease during a relatively complex motor task. MATERIALS AND METHODS: Seven patients (six men and one woman) with lateralised akinetic-rigid Parkinson's disease underwent functional magnetic resonance imaging (MRI) of the brain with a 1.5-T magnet. Finger tapping was chosen as a motor task. The control group included 11 volunteers (six men and five women) with no neurological disease. RESULTS: Patients showed hyperactivity of the ipsilateral and contralateral motor cortex associated with bilateral over-activation of the parietal cortex during movement of the affected hand. In some cases, there was a lack of activation of the pre-motor and supplementary motor areas whereas, when present, activation in these areas was greater during movement of the healthy hand. Finally, activation of the occipital cortex was found in all patients as a result of their tendency to control movement visually. CONCLUSIONS: Results of this study confirm a re-organisation of cortical circuits due to subcortical damage in patient's with Parkinson's disease.

Adult↗

End-user survey for digital sensor characteristics: a pilot questionnaire study.

OBJECTIVE: To survey end-user opinions on dental digital sensor characteristics for the design of a new X-ray imaging sensor. MATERIALS AND METHODS: 100 questionnaires were sent out to dentists and dental radiologists. The questionnaire consisted of six parts related to dental sensors. A: Details about the respondent; B: Prioritization of most important aspects of digital sensors; C: Rating advantages and D: disadvantages of digital sensors; F: Dental features that need to be enhanced by digital sensors; G: End-user comments. RESULTS: Fifty-six questionnaires were returned. Contrast resolution and imaging time were assessed as the most and the least important aspects, respectively. Aspects considered as advantages by approximately 80% of respondents were: optimal contrast resolution, increased specificity, increased discrimination between diseased and healthy tissue, increased sensitivity, lower dose to the patient by more than 20%; as a disadvantage, increased patient dose was given. Dental features considered important by over 80% of the respondents were for intraoral radiographs: the visibility of caries, periapical, periodontal, and bone lesions; for panoramic radiographs: reduction of ghost images, image sharpness and bone. Bone and soft tissues on cephalograms and bone on temporomandibular joint (TMJ) tomograms were mentioned by over 70%. CONCLUSION: The most desired characteristic for a new sensor is contrast resolution. Dose saving is not considered as important unless it is more than 20%. Examination time is not a major issue. Caries, periapical and periodontal, and bone lesions for intraoral radiographs, reduction of ghost images, image sharpness and bone for panoramic radiographs were the most frequently mentioned dental features that should be enhanced by digital sensors.

Artifacts↗

Gefitinib (ZD1839) combined with weekly epirubicin in patients with metastatic breast cancer: a phase I study with biological correlate.

PURPOSE: Epidermal growth factor receptor (EGFR) is overexpressed in approximately 50% of invasive breast carcinomas and it is correlated with hormone resistance and poor prognosis. EGFR suppression by gefitinib, a quinazoline derivative that inhibits phosphorylation of the specific receptor, represents a novel therapeutic strategy. A dose-finding study was performed to evaluate the combination of gefitinib with weekly epirubicin in patients with pretreated metastatic breast cancer. METHODS: Fifteen patients were enrolled at four sequential dose levels. Gefitinib was administered orally, at the fixed daily dose of 250 mg. The starting dose of epirubicin was 20 mg/m2. Escalating dose levels of epirubicin were planned by increments of 5 mg/m2 per level, up to the maximum tolerated dose (MTD). Pharmacodynamic studies were performed by determining serum and tissue ERBB2 and EGFR. RESULTS: At the first three dose levels tested no patient experienced a dose-limiting toxicity (DLT). In cohort 4, two patients experienced DLTs (grade 4 dyspnea and asthenia, grade 3 diarrhea and thrombocytopenia) identifying the MTD of epirubicin as 35 mg/m2. Of the 14 cases assessable for response, partial response was documented in two patients, and stable disease in seven, giving an overall disease control rate of 64.2%. The comparison of pre- and post-therapy ERBB2 and EGFR values was not statistically significant between the subgroups of patients regarding responsiveness to treatment. CONCLUSIONS: The recommended dose of epirubicin for phase II studies is 30 mg/m2 in combination with gefitinib at the daily dose of 250 mg. Pharmacodynamic studies did not identify any biomarker predictive of response.

Adult↗

High resolution Ca/P maps of bone architecture in 3D synchrotron radiation microtomographic images.

The Ca/P ratio was measured in cortical bone samples from the femoral neck and tibia of different animal species, using synchrotron radiation microtomography. Use of a monoenergetic X-ray beam, as provided by the synchrotron facility, generates accurate 3D maps of the linear attenuation coefficient within the sample and hence gives the ability to map different chemical components. Also, by comparing normal and abnormal bones, i.e. osteoporotic (induced by inflammation), changes in the Ca/P ratio brought about by bone diseases can be detected. MicroCT data sets were collected at 20 and 28 keV for each bone sample and two calibration phantoms. From the 3D data sets, multiple 2D slices were reconstructed with a slice thickness of approximately 30 microm. Regions of interest were defined around suitable sites and were converted to Ca/P ratios using the data collected from the test phantoms. A significant difference (p<0.001) between osteoporotics and age-matched normals at both energies was detected. Differences between different bone sites from the same animal are not significant (p>0.5) while those between the same bone sites from different animals are highly significant (p<0.001). Differences between estimates made at 20 and 28 keV are not significant (p>0.5). An important aspect is the ability to map the spatial distribution of the Ca/P ratio.

Animals↗

Clinical benefit of intermittent administration of imatinib in a patient with metastatic gastrointestinal stromal tumour.

Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours of the gastrointestinal tract, resistant to conventional chemotherapy and radiotherapy, but responsive to imatinib. Acquired resistance to imatinib has been reported in some patients, and several studies have suggested the possibility of overcoming imatinib resistance by increasing the dose of the drug. This case shows the possibility of obtaining clinical benefit with intermittent administration of imatinib in a patient who developed acquired resistance to a high dose of the drug.

Aged↗

Therapy of breast cancer with molecular targeting agents.

Invasive breast cancer is a heterogeneous disease sustained by intercorrelated and complex growth pathways. Classically, human breast carcinoma has been classified for therapeutic purposes in two distinct categories: one hormone-correlated, the other hormone-uncorrelated. However, the recent advancements of the technology applied to molecular biology by genomic and proteomic analyses have suggested that many more factors are involved in breast cancer growth and progression and that some clusters of these distinguish subgroups of patients at different prognosis. The knowledge of the diversities between tumor and normal tissue of origin is the key to identify novel targets for new selective therapeutic strategies. In fact, the principal goal of molecular-targeted therapy is the suppression of the transformed phenotype minimally affecting normal cells. This review focuses on the molecular targeting compounds directed against the known molecular pathways involved in breast cancer such as: type I growth factors (HER-2/neu; epidermal growth factor receptor [EGFR]), angiogenesis, cyclooxigenase-2 (COX-2) and farnesylation. Presently, trastuzumab is the first agent approved for therapy of HER-2/neu overexpressing tumors. Several other compounds directed against different targets have entered clinical evaluation and the preliminary results are here presented and commented. The major challenges on the clinical development of targeted therapy include the proper selection of patients, the identification of the optimal dosage and schedule of administration, the combinations with conventional treatments and the more appropriate therapeutic strategy.

Angiogenesis Inhibitors↗

Long-term follow-up of a pilot phase II study with neoadjuvant epidoxorubicin, etoposide and cisplatin in gastric cancer.

OBJECTIVE: The prognosis in T3-T4 or N+ gastric cancer is dismal, and the role of adjuvant therapy remains uncertain. Neoadjuvant chemotherapy could improve both resectability and survival. Here, we report the results of the long-term follow-up of a pilot study aimed at evaluating a neoadjuvant treatment in a group of patients carefully staged by computed tomography (CT), endoscopic ultrasound and laparoscopy. METHODS: Twenty-five stage II-III patients with histologically proven gastric adenocarcinoma were enrolled in the study. All patients gave informed consent and were thoroughly staged. Patients were treated with epidoxorubicin (40 mg/m2 i.v.) on days 1 and 4, etoposide (VP-16; 100 mg/m2) on days 1, 3 and 4 and cisplatinum (80 mg/m2) on day 2, every 21-28 days for 3 pre-operative cycles before CT clinical restaging followed by laparotomy and D2 gastrectomy. Three further cycles of chemotherapy were planned after radical surgery. RESULTS: Twenty-four patients received the planned pre-operative chemotherapy and underwent surgical resection; total (13 patients) or subtotal (7 patients) R0 D2 gastrectomy was possible in 20 patients. One patient died as a result of gastric bleeding. Perioperative complications occurred in 5 patients (failure of anastomosis in 1 patient and wound infection in the other 4). The pathologic response rate included 7 partial responses (29.1%) and 10 patients with stable disease (41.7%). The main toxicity was grade 3/4 neutropenia (68%), which occurred more frequently during the postoperative chemotherapy, and fatigue (68%). Fever or infection, however, were never observed. The median disease-free survival was 37 months, and median survival has not been reached after 40 months of median follow-up. One-, 2- and 3-year survival rates were 80, 64 and 60%, respectively. CONCLUSION: The notable long-term survival in the present study suggests a comparison between the neoadjuvant approach, including new drug combinations, and adjuvant chemo- or chemoradio-therapy in locally advanced gastric cancer.

Adenocarcinoma↗

Corticobasal degeneration: structural and functional MRI and single-photon emission computed tomography.

We studied seven patients with corticobasal degeneration (CBD) from a clinical and imaging perspective. We describe the main morphological features of CBD and, using functional MRI, try to define the possible role of the parietal lobe in simple and complex learned motor sequences. We showed decreased activation of the parietal lobe contralateral to the more affected arm, when movements, simple or complex, are performed with that hand. Moreover we found that functional imaging can demonstrate parietal and motor cortex dysfunction before structural, and even single-photon emission computed tomography changes become evident.

Aged↗

Weekly gemcitabine and 24-hour infusional 5-fluorouracil in advanced pancreatic cancer: a phase I-II study.

OBJECTIVE: In this phase I-II study we explored the potential of the combination of weekly gemcitabine (GEM) and 24-hour continuous infusion of 5-fluorouracil (5-FU) in order to determine the toxicity profile in pancreatic cancer. The efficacy of this drug combination was studied as a secondary endpoint. METHODS: Twenty-one patients with histologically or cytologically proven unresectable or metastatic previously untreated pancreatic adenocarcinoma were included in this study. Two dose levels of GEM and two dose levels of 5-FU were evaluated in three cohorts of patients who received GEM 1,000 mg/m(2) and 5-FU 2,000 mg/m(2), GEM 1,200 mg/m(2) and 5-FU 2,000 mg/m(2), or GEM 1,200 mg/m(2) and 5-FU 2,250 mg/m(2), on days 1, 8, and 15, every 4 weeks, respectively. RESULTS: Grade 3-4 neutropenia was observed in 10% of the cycles. Non-myelosuppressive toxicities included fatigue (22%), grade 1-2 diarrhea (12%) and grade 1 liver toxicity. There was no limiting toxicity and the maximum tolerated dose has not been reached. Two patients experienced a partial response (9.5 +/- 12.6%) and 12 patients had stable disease (57.1 +/- 21.2%). Seven of the 14 symptomatic patients improved their disease-related symptoms and 4 of the 8 patients evaluable for clinical benefit had a clinically beneficial response (50 +/- 34.6%). The median progression-free survival was 6 months (range 2-28), median survival was 11 months (range 3-32+), and the actuarial 1-year survival rate 33%. CONCLUSION: The weekly administration of GEM combined with 24-hour continuous infusion of 5-FU shows a good safety profile at the dose levels evaluated. Some partial responses had also been achieved, disregarding the dose level of the two drugs. Survival confirms the activity of this drug combination.

Adult↗

Signal-to-noise ratio evaluation in dual-energy radiography with synchrotron radiation.

Dual-energy radiography is an effective technique that allows removal of contrast between pairs of materials in order to display details of interest on a uniform background. In mammographic images the detection of small nodules is often impeded by obscuring background 'clutter' resulting from the contrast between normal tissues (glandular and adipose) in their neighbourhood. We consider whether it could be possible to apply dual-energy radiography to the breast, which is hypothetically principally composed of three tissues, glandular, adipose and cancerous, in order to remove the contrast due to the distribution of normal tissues and, as a consequence, to enhance the intrinsic contrast of the pathology. The purpose of this work is to test the limitations of dual-energy radiography on a three-component phantom under optimum conditions of the source and detector. We use a synchrotron monochromatic beam, produced at the ELETTRA synchrotron facility (Trieste, Italy), and an imaging plate detector, in order to acquire two images at low and high energies of a phantom composed of polyethylene, plexiglas and water. For evaluation of the potential of this procedure we studied the signal-to-noise ratio (SNR) of polyethylene and water on a set of images obtained by applying the dual-energy procedure. We found that the SNR of polyethylene and water is around the detectability threshold (according to Rose's criteria) at the contrast cancellation angles. Finally we evaluated the air entrance dose required for this double exposure, resulting in 0.81 mGy for the low-energy image and 0.01 mGy for the high-energy image. To obtain the same image quality for a standard breast of 5.5 cm, mean glandular doses of 3.50 mGy and 0.03 mGy at 17 keV and at 34 keV, respectively, are required.

Algorithms↗

Preliminary study on extremely small angle x-ray scatter imaging with synchrotron radiation.

Among the medical physics community, there is nowadays a great interest in the possible implementation of scatter imaging techniques, especially in the field of breast imaging. It is well known that malignant lesions and normal tissue differ in their scattering signatures, and thus scattered radiation can provide a powerful tool to distinguish between the two cases. Up to now, most of the proposed techniques rely on the detection of radiation scattered at angles of the order of a few degrees, which in most cases results in very high contrast values. On the other hand, at those relatively large angles the scattered flux is relatively low with respect to the primary, which often implies the necessity of increasing the dose delivered to the sample in order to achieve sufficient statistics. Furthermore, most of these techniques are based on pencil beam set-ups, which results in an increase of the overall duration of the examination. We propose here an alternative approach based on the detection of radiation scattered at extremely small angles, of the order of approximately 100-200 microrad. This results in a relatively high scattered flux (5-10% of the primary) and in the possibility of utilizing a fan beam geometry, which reduces the acquisition times with respect to pencil beam set-ups. Images of several samples have been acquired, demonstrating that the proposed technique results in an increased contrast with respect to absorption imaging. Possible in vivo implementations of the technique at no dose expense are finally discussed.

Algorithms↗

Antioxidant activity of propolis: role of caffeic acid phenethyl ester and galangin.

Propolis, a natural product produced by the honeybee, has been used for thousands of years in folk medicine for several purposes. The extract contains amino acids, phenolic acids, phenolic acid esters, flavonoids, cinnamic acid, terpenes and caffeic acid. It possesses several biological activities such as antiinflammatory, immunostimulatory, antiviral and antibacterial. The exact mode of physiological or biochemical mechanisms responsible for the medical effects, however, is yet to be determined. In this work, we have investigated the antioxidant activity of a propolis extract deprived of caffeic acid phenethyl ester (CAPE). In addition, the activity of CAPE and galangin was also examined. Propolis extract (with and without CAPE) and its active components showed a dose-dependent free radical scavenging effect, a significant inhibition of xanthine oxidase activity, and an antilipoperoxidative capacity. Propolis extract with CAPE was more active than propolis extract without CAPE. CAPE, used alone, exhibited a strong antioxidant activity, higher than galangin. The experimental evidence, therefore, suggests that CAPE plays an important role in the antioxidant activity of propolis.

Antioxidants↗

Anti-angiogenic therapy: rationale, challenges and clinical studies.

Physiological angiogenesis occurs during embryogenesis, wound healing and reproductive functions in adults. Abnormal angiogenesis takes place in certain chronic diseases (diabetes, psoriasis, rheumatoid arthritis, etc.) and tumours. Genetic changes and local stresses including hypoxia, glucose deprivation and oxidative stress play a pivotal role in angiogenesis switch, which is necessary for tumour development and is rate-limiting for tumour progression. Angiogenesis is tightly regulated by pro- and anti-angiogenic growth factors with a series of complex and interrelated steps. Activated endothelial cells (ECs) migrate as a solid cord and, subsequently, form lumina; the sprout tips then anastomose to form vessel loops or networks. One of the final events is the laying down of a basement membrane and the structural support of pericytes. The molecular alterations that sustain angiogenesis represent novel targets for rationally designed anti-cancer treatment strategies. Inhibition of angiogenesis presents certain advantages on conventional therapies, such as the direct accessibility from the circulation, and the potential low rate of drug resistance related to the genetic stability of ECs. Certain anti-angiogenic compounds were found to have potent anticancer property in in vivo experimental studies. Nevertheless, in contrast to preclinical studies, the first generation of anti-angiogenic drugs tested in clinical trials have shown a moderate activity in advanced disease partly due to suboptimal schedules of therapy or biases in study design.

Angiogenesis Inhibitors↗

Learned movements in a left-handed pianist: an f-MRI evaluation.

The spatial arrangement of neuronal sources for digit movement is non somatotopic, and is structured as extensively arranged through different regional cortex. We have functionally examined the cerebro-cortical activation during simple and complex motor sequences, before and after learning sessions, in healthy volunteers, both considering left- and right-dominant hand use, and left non dominant hand use, skillfulness and educational level. We discuss the results with a review on the topic.

Adult↗