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Biomedical subjects

C Rossi

Publications and source records attributed to C Rossi.

At least 55 records · Page 3Linked to original sources

Dopaminergic degeneration and perfusional impairment in Lewy body dementia and Alzheimer's disease.

The clinical differentiation of Lewy body dementia (LBD) from Alzheimer's disease (AD) may be difficult. The aim of the present study was to assess the dopamine transporter function and the perfusional pattern in LBD and AD in vivo. Twenty patients with probable LBD and 24 with probable AD underwent on 2 separate days a brain perfusional SPECT with 99mTc-ECD and a SPECT with (123)I-FP-CIT, a ligand of dopamine transporter. In LBD a significantly ( p<0.0005) lower ratio of specific (bilateral caudate nucleus, putamen) to non-specific (occipital cortex) (123)I-FP-CIT binding than in AD was reported. Perfusional data (SPM analysis) showed a significant ( p<0.001) decrease of temporo-parietal blood flow in AD versus LBD, whereas in LBD a significant ( p<0.001) occipital hypoperfusion with respect to AD was reported. Our findings confirm that dopaminergic nigrostriatal function is impaired in LBD. The selective occipital hypoperfusion in LBD needs to be further investigated.

Aged↗

Persistent activation of p38 mitogen-activated protein kinase in a mouse model of familial amyotrophic lateral sclerosis correlates with disease progression.

The p38 mitogen-activated protein kinase (p38MAPK) is activated via phosphorylation in neurones and glial cells by a variety of stimuli including oxidative stress, excitotoxicity, and inflammatory cytokines. Activated p38MAPK can in turn induce phosphorylation of cytoskeletal proteins and activation of cytokines and nitric oxide, thus contributing to neurodegeneration. We investigated the expression and distribution of p38MAPK in the spinal cord of transgenic mice expressing a superoxide dismutase 1 mutation (SOD1G93A), a model of familial amyotrophic lateral sclerosis (ALS). Accumulation of p38MAPK was found by immunoblotting in the spinal cord of G93A mice during the progression of disease, but no changes were detected in its mRNA levels. Immunostaining for phosphorylated p38MAPK in lumbar spinal cord sections of SOD1G93A mice at the presymptomatic and early stages of disease showed an increased labeling in motor neurones that colocalized with phosphorylated neurofilaments in vacuolized perikarya and neurites, as detected by confocal microscopy. As the disease progressed, activated p38MAPK also accumulated in hypertrophic astrocytes and reactive microglia, as demonstrated by colocalization with GFAP and CD11b immunostaining, respectively. These data suggest that activation of p38MAPK in motor neurons and then in reactive glial cells may contribute, respectively, to the development and progression of motor neuron pathology in SOD1G93A mice.

Amyotrophic Lateral Sclerosis↗

Evolutionary Local Search of Fuzzy Rules through a novel Neuro-Fuzzy encoding method.

This paper proposes a new approach for constructing fuzzy knowledge bases using evolutionary methods. We have designed a genetic algorithm that automatically builds neuro-fuzzy architectures based on a new indirect encoding method. The neuro-fuzzy architecture represents the fuzzy knowledge base that solves a given problem; the search for this architecture takes advantage of a local search procedure that improves the chromosomes at each generation. Experiments conducted both on artificially generated and real world problems confirm the effectiveness of the proposed approach.

Algorithms↗

Atypical antibody responses in dengue vaccine recipients.

Eight of 69 (12%) healthy adult volunteers vaccinated with monovalent live-attenuated dengue virus (DENV) vaccine candidates had atypical antibody responses, with depressed IgM:IgG antibody ratios and induction of high-titer hemagglutination-inhibiting and neutralizing (NT) antibodies to all four DENV serotypes. These features suggested flavivirus exposure prior to DENV vaccination, yet no volunteer had a history of previous flavivirus infection, flavivirus vaccination, or antibody to flaviviruses evident before DENV vaccination. Moreover, production of antibody to DENV by atypical responders (AR) was not accelerated compared with antibody responses in the 61 flavivirus-naive responders (NR). Further evaluation revealed no differences in sex, age, race, DENV vaccine candidate received, or clinical signs and symptoms following vaccination between AR and NR. However, viremia was delayed at the onset in AR compared with NR. A comparative panel of all AR and five randomly selected NR found flavivirus cross-reactive antibody after vaccination only in AR. Unexpectedly, six of eight AR had NT antibodies to yellow fever virus (YFV) > 1:10 before vaccination while NR had none (P = 0.04). The AR also universally demonstrated YFV NT antibody titers > or = 1:160 after DENV vaccination, whereas four of five NR failed to seroconvert (P = 0.02). Yellow fever virus priming broadens the antibody response to monovalent DENV vaccination. The effect of flavivirus priming on the clinical and immunologic response to tetravalent DENV vaccine remains to be determined.

Adolescent↗

[Status of low-vision rehabilitation for age-related macular degeneration by orthoptists in the North of France].

AIM OF THE STUDY: To evaluate the status of low-vision rehabilitation carried out by the orthoptists in the North of France. This study was a preliminary step in setting up a network between different vision professionals for the management of age-related macular degeneration (AMD) the North of France. METHODS: The ASO (Association Septentrionale d'Ophtalmologie) conducted a survey funded by the URCAM (Union Régionale des Caisses d'Assurance Maladie) with the FAQSV (fond d'aide à la qualité des soins de ville). The survey was based on the analysis of two forms sent to orthoptists of the North region of France. RESULTS: The survey analyzed 46 responses (a representative sample with 69% responses) providing a description of the orthoptists of the North of France: 19% males, 81% females whose mean professional experience was 13.3 years. Thirty-four percent of the orthoptists have had training in low-vision rehabilitation. This training was given during the university courses for 21% of responders and during a postgraduate course for 79%. Of the orthoptists surveyed, 64% worked in a private context, 9% in a public context, and 27% in both public and private contexts. Their main activity was in their own private practice for 60%, in an ophthalmologist's office for 20%, in a public institution for 16%, and a private institution for 4%. The mean number of patients treated was 70 per week per orthoptist, with 21% working mostly with children, 36% working mainly with adults between 16 and 60 years of age, and 7% with the elderly, whereas 36% reported no specificity related to patient age. The mean number of patients dealt with for low vision related to AMD was 4.1 per month per orthoptist. The average number of patients dealt with for low vision with no relation to AMD was 1.5 per month. The prescriber of low-vision rehabilitation was an ophthalmologist for 88.9% of the orthoptists and a general practitioner for 11.1%. Questions addressed to AMD patients: at the beginning of the survey, 83.8% of the patients did not have sufficient visual acuity to be able to read a text of current size (Parinaud 4); 40.4% of the patients required help for everyday life, and 59.6% were autonomous. For 7.1% of the patients, low-vision rehabilitation was carried out less than 1 month after the stabilization of retinal lesions, but in 35.3%, rehabilitation was carried out more than 2 years after lesions were stabilized. The main request of the patients involved improvement of near vision (89.9%). CONCLUSION: This survey will be a preliminary step in setting up a regional health network coordinating the ophthalmological and orthoptic management of AMD.

Aged↗

Upper respiratory tract infections and pediatric anesthesia.

Anesthesia for the child with an upper respiratory infection (URI) presents a challenge for the pediatric anesthesiologist. Differences in study design have made interpretation and comparison very difficult. The general lack of evidence-based research has led to disparities in the manner in which children which URI have been traditionally managed. Many studies have described associations between URIs and adverse events and we must decide whether to proceed or postpone the procedure and how long to postpone it. More recent research, however, suggests that children with uncomplicated infections can undergo elective procedures without significant increase in adverse anesthetic outcomes. This presentation summarizes the evolving literature about cancellation of surgery for the child with an upper respiratory infection, perioperative outcomes and anesthetic management.

Anesthesia↗

Use of sedative and analgesic drugs in the first week of ICU stay in high-level-of-care.

AIM: The aim of this study was to update the current practice of pharmacological sedation and analgesia in Italian intensive care units. METHODS DESIGN: observational, prospective, cohort study involving consecutive patients admitted during 5 months in 1999. PATIENTS were evaluated for the first 7 days of high-level-of care. SETTING: 45 adult general intensive care units. PATIENTS: 388 fulfilling enrollment criteria: admission diagnosis out of non-traumatic cerebral hemorrage, stroke, respiratory failure in chronic obstructive pulmonary disease (COPD), acute lung injury/distress syndrome (ALI/ARDS), polytrauma, head trauma, cardiac failure and major abdominal surgery; unit stay longer than 47 hours and high-level-of care treatment. RESULTS: Sedation pattern was different among diagnosis-groups. No therapy was registered in 18.8% of overall days in polytrauma vs 67.6% of cardiac patients. Opioids supply ranged from 10.1% of overall days of acute on COPD patients vs 51.4% of polytrauma patients. Propofol was the more prescribed drug, followed by opioids and benzodiazepines. Propofol was at the top in cerebrovascular disease, ALI/ARDS and COPD; opioids in abdominal surgery and trauma, benzodiazepines in cardiac failure. The average number of prescribed drugs per day was 1.5 ranging from 1.2 on COPD to 1.7 in head trauma. CONCLUSION: Diagnosis influences the pattern of sedation-analgesia during high-level-of-care period. Sedation prevalence is reasonably prescribed in trauma groups while it remains low in ALI/ARDS, post-operative, cerebrovascular, COPD and hearth failure. Particularly opioid use remains limited in post-operative patients. This surveys shows a poorly standardised sedation approach to the different phases of the therapy: induction, short and long-term sedation phase.

Analgesia↗

Intraoperative radiation therapy for retroperitoneal soft tissue sarcomas.

Treatment of retroperitoneal soft tissue sarcomas is a difficult clinical problem. Despite the improvement in resection rates in the most recent surgical series, local control still remains the main problem because of the high incidence of local recurrences after surgery. Postoperative radiation therapy has not been always successful because of dose-tolerance of surrounding normal structures, which prevent the delivery of adequate doses of radiation. To overcome this limitations, new therapeutic approaches including external-beam radiation and intraoperative radiation therapy (IORT) have been evaluated at some Institutions. The results of IORT with or without external-beam radiation are reviewed and our experience with preoperative radiation and IORT is reported. As treatment of retroperitoneal sarcomas has evolved into combined modalities including preoperative radiation, maximum surgical resection and IORT, a possible improvement in local control rates has been achieved. However, locoregional failures and the incidence of distant metastases remain a challenge, emphasising the need for further improvement in local and distant treatment. The new phase II trial, activated within the Italian Sarcoma Group, with preoperative concurrent chemo-radiation therapy and IORT is presented.

Combined Modality Therapy↗

New microencapsulated sunscreens: technology and comparative evaluation.

The aim of this work is to obtain new technologically improved microencapsulated sunscreens characterised by UV-radiation stability, good substantivity, low toxicity, a better tolerability and easiness to formulation. For this purpose we prepared two different systems using semisynthetic Hyaluronic Acid (HA) benzyl ester and a synthetic polymer (patent pending). We obtained these systems using two different methodologies: emulsification/solvent evaporation and emulsification/solvent extraction. The comparison between the two formulated systems was carried out in terms of their chemical-physical and biological properties.

Capsules↗

Mesorectal microfoci adversely affect the prognosis of patients with rectal cancer.

PURPOSE: Mesorectal involvement is a common feature in rectal tumors. Neoplastic foci can be identified at pathologic examination of the mesorectum, but their incidence and prognostic significance remain to be defined. METHODS: A series of 77 patients with extraperitoneal rectal cancer, resected with total mesorectal excision, entered the study. After fixation, the excised specimens were submitted to serial transverse sections and staining. Direct tumor infiltration, lymph node involvement, and neoplastic microfoci in the mesorectum were investigated. Patients with mesorectal foci were compared with those without deposits with regard to clinical and pathologic parameters; different patterns of foci (endovasal, endolymphatic, perineural, isolated) were also considered. Univariate and multivariate analyses were used to evaluate the impact on survival rate. RESULTS: Neoplastic mesorectal involvement was found in 64 patients (83.1 percent). Direct tumor infiltration was detected in 66.2 percent, node involvement in 28.6 percent, microscopic foci in 44.2 percent of cases (endovasal in 11.7 percent, endolymphatic in 15.7 percent, perineural in 26 percent, isolated in 14.3 percent). In 7 cases (10.9 percent) microfoci alone (without any kind of other mesorectal involvement) were detected. Deposits were found in 18.8 percent of TNM Stage I tumors, in 46.9 percent of Stage II and in 59.3 percent of Stage III cancers. Similar incidence was found in patients treated with integrated therapies and surgery alone (43.3 vs. 44.7 percent, P = not significant). Poorer median (44.5 vs. 57 months, P = 0.04) five-year overall survival rate (43.4 vs. 63.3 percent, P = 0.016) and disease-free survival rate (43.3 vs. 57.7 percent, P = 0.048) were observed in patients with microscopic foci compared with those without deposits. Tumor configuration was found to be a independent prognostic factor for both overall and disease-free survival rates; furthermore, endolymphatic, perineural, and isolated foci significantly affected overall survival rate, while TNM staging affected disease-free survival rate. CONCLUSIONS: The incidence of neoplastic foci in the mesorectum is high, even in early staged tumors and despite aggressive preoperative treatment. They seem to affect prognosis. Such features should, therefore, be considered when local excision of the tumor is planned. Presence of mesorectal foci should modify conventional staging of the rectal tumor.

Adult↗

Inhibition of telomerase activity by a distamycin derivative: effects on cell proliferation and induction of apoptosis in human cancer cells.

In this study, we evaluated the potential of the distamycin derivative MEN 10716 as a telomerase inhibitor. Exposure of human melanoma cell extracts to MEN 10716 induced a dose-dependent inhibition of telomerase activity, with an IC50 of 24+/-3 microM. When intact JR8 melanoma cells were chronically exposed to the drug (200 microM every other day for 50 days), a marked inhibition (>80%) of the enzyme's catalytic activity was consistently observed starting from day 1. At later points in time, MEN 10716 inhibited melanoma cell proliferation and induced apoptosis. Cells surviving MEN 10716 exposure were characterised by a higher melanin content and a greater expression of p16(INK4A) protein than control cells. The effects of MEN 10716 were subsequently evaluated in different tumour cell systems. In particular, even in the H460 non-small cell lung cancer cell line, chronic exposure of the cells to the drug (100 microM every other day for 50 days) induced a consistent inhibition (>85%) of telomerase activity, a reduction of cell proliferation potential, and apoptosis. Conversely, MEN 10716 treatment did not appreciably inhibit cell proliferation in the U2-OS telomerase-negative human osteogenic sarcoma cell line. Interestingly, no variation in the mean telomere length was observed in MEN 10716-treated JR8 melanoma cells, whereas an appreciable increase in the mean telomere length was found in H460 lung cancer cells after drug exposure. Overall, the results of the study indicate that MEN 10716 is a possible telomerase inhibitor and suggest that abrogation of telomerase activity can affect cell proliferation even through pathways that are not dependent on telomere erosion.

Antineoplastic Agents↗

Prognostic factors in soft tissue sarcomas: a study of 395 patients.

AIMS: The aim of this study was to report prognostic factors, end-points of local recurrence, distant recurrence, post-metastasis survival, and overall survival in a cohort of patients with soft tissue sarcomas. METHODS: We analysed a database of 395 patients affected by primary soft tissue sarcomas of various primary sites, treated and followed up at the Centro di Riferimento Oncologico, Aviano, Italy from January 1985 to January 1997. RESULTS: Grade, size, stage, surgical margins, distant metastasis, age, sex, performance status, and haemoglobin value were significant for overall survival. Histology, grade, stage, and surgical margins were significant for local recurrence. Grade, size, and stage, were significant for distant recurrence; and surgical margin was significant variable for post-metastasis survival. CONCLUSIONS: Grade, size, and TNM stage (UICC/AJCC) have stronger prognostic significance for overall survival and distant recurrence than for local relapse. Positive surgical margins are the main predictors for local relapse. Age was the most consistent adverse independent prognostic factor for survival.

Adolescent↗

Bruno de Finetti: the mathematician, the statistician, the economist, the forerunner.

Bruno de Finetti is possibly the best known Italian applied mathematician of the 20th century, but was he really just a mathematician? Looking at his papers it is always possible to find original and pioneering contributions to the various fields he was interested in, where he always put his mathematical "formamentis" and skills at the service of the applications, often extending standard theories and models in order to achieve more general results. Many contributions are also devoted to educational issues, in mathematics in general and in probability and statistics in particular.He really thought that mathematics and, in particular, those topics related to uncertainty, should enter in everyday life as a useful support to everyone's decision making. He always imagined and lived mathematics as a basic tool both for better understanding and describing complex phenomena and for helping decision makers in assuming coherent and feasible actions. His many important contributions to the theory of probability and to mathematical statistics are well known all over the world, thus, in the following, minor, but still pioneering, aspects of his work, related both to theory and to applications of mathematical tools, and to his work in the field of education and training of teachers, are presented.

Economics↗

Radiotherapy and continuous infusion 5-fluorouracil in patients with nonresectable pancreatic carcinoma.

PURPOSE: The current standard local treatment for nonresectable pancreatic carcinoma is radiotherapy (RT) with concurrent 5-fluorouracil (5-FU); however, the optimal schedule for 5-FU administration has not been fully established. In this study, we report on our experience with the combination of RT and continuous infusion 5-FU in a group of patients with locally nonresectable pancreatic carcinoma. METHODS AND MATERIALS: Forty-two patients with adenocarcinoma of the pancreas were enrolled in a prospective clinical trial. RT was delivered using a four-field technique to a total dose of 59.4 Gy in 33 fractions. 5-FU was given through a central venous catheter at a dose of 300 mg/m(2)/day, 7 d/wk, throughout the entire course of RT. RESULTS: All patients completed the RT as planned, and 33 (78%) completed the full regimen of chemotherapy. Ten patients (23%) had a partial response, and 32 (77%) had stable disease. Subjective response, defined as the disappearance of symptoms observed at diagnosis, was also evaluated. Two patients (6%) had a complete, and 24 (75%) a partial, remission of symptoms. The median time to progression was 6.2 months, and the median survival time was 9.1 months. CONCLUSIONS: In terms of local control, the results of our study, with RT and protracted 5-FU infusion, compare well with those of other studies using RT and bolus 5-FU. The control of distant metastatic disease remains an open issue. However, the palliation of symptoms achieved by our treatment schedule in patients with a very poor prognosis and severe symptoms may be regarded as a positive result.

Adenocarcinoma↗

Improved function of rat islets upon co-microencapsulation with Sertoli's cells in alginate/poly-L-ornithine.

The purpose of this study was to assess whether Sertoli's cells would improve functional performance of homologous pancreatic islets within microcapsules. Purified rat Sertoli's cells were co-enveloped with islets in microcapsules that had been fabricated with alginic acid and poly-L-ornithine. Confocal laser microscopy was used to determine any mitogenic effects of Sertoli's cells on islets beta-cells. Insulin secretion from islets, with or without Sertoli's cells, was examined, and grafts of Sertoli's cells with islets in microcapsules into diabetic mice were carried out. Co-incubation of Sertoli's cells with islets resulted in a significant increase in the islet beta-cell mitotic rate, which was coupled with significantly higher insulin release under glucose stimulation, as compared to controls. Grafts of co-microencapsulated Sertoli's cells with islets resulted in prolongation of the achieved normoglycemia in the animals receiving Sertoli's cells with islets as compared to controls that received islets only. Sertoli's cells do promote mitogenic activities upon in vitro co-incubation with islets, whose in vitro functional and in vivo post-transplant consequences were evident. Sertoli's cells could, therefore, be co-microencapsulated with islets for transplantation in diabetic recipients.

Alginates↗

Fatal primary infection due to human herpesvirus 6 variant A in a renal transplant recipient.

We describe a fatal primary human herpesvirus 6 (HHV-6) variant A infection in a kidney transplanted adult woman. On day 20 post transplantation (TX), after rejection therapy, the patient presented an acute hemophagocytic syndrome with hepatitis and central nervous system involvement. HHV-6 IgG and IgM antibodies seroconversion was demonstrated. HHV-6 variant A was the sole pathogen detected by nested PCR and/or culture in blood, bone marrow aspiration, liver biopsy, cerebrospinal fluid and bronchoalveolar lavage. The graft was HHV-6 seropositive and the patient was not transfused before day 28 post TX, suggesting that the virus was transmitted by the graft. Despite immunoglobulins, ganciclovir and foscarnet therapy, the HHV-6 infection progressed and led to severe aplasia. The patient developed Aspergillus fumigatus pneumonia and died from fulminant candidemia. This case demonstrated for the first time that HHV-6 variant A primary infection can cause life-threatening disseminated infection in immunosuppressed patients.

Adult↗