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Biomedical subjects

G Rossi

Publications and source records attributed to G Rossi.

At least 73 records · Page 4Linked to original sources

Darbepoetin alfa administered every 3 weeks alleviates anaemia in patients with solid tumours receiving chemotherapy; results of a double-blind, placebo-controlled, randomised study.

This dose-finding, placebo-controlled study evaluated the safety and efficacy of darbepoetin alfa administered every 3 weeks (Q3W) to anaemic patients receiving chemotherapy. In part A, patients (haemoglobin </=110 g/l) were randomised in a 1:4 ratio to receive 1 of 6 doses of darbepoetin alfa (4.5, 6.75, 9.0, 12.0, 13.5 and 15.0 microg/kg) or placebo Q3W for 12 weeks. In part B, patients received open-label darbepoetin alfa. Patients (n=249) were evaluated for safety, haemoglobin endpoints and red blood cell (RBC) transfusions. Darbepoetin alfa given at doses ranging from 4.5 to 15.0 microg/kg Q3W was well tolerated and comparable to placebo in terms of safety. No neutralising antibodies were detected. All doses (from 4.5 to 15 microg/kg) reduced transfusions compared with placebo, and resulted in >50% of patients achieving a haematopoietic response. Administration of darbepoetin alfa Q3W has a tolerable safety profile and effectively ameliorates anaemia due to chemotherapy.

Adult↗

Successful T-cell-depleted, related haploidentical peripheral blood stem cell transplantation in a patient with Fanconi anaemia using a fludarabine-based preparative regimen without radiation.

Haematopoietic stem cell transplantation (HSCT) represents the treatment of choice for severe bone marrow failure in patients with Fanconi anaemia (FA). When the donor is a compatible relative, the chance of being cured with an allograft is in the order of 70%. However, for FA children lacking an HLA-identical sibling, the results of HSCT from an alternative donor are less satisfactory because of a higher risk of graft rejection, graft-versus-host-disease (GVHD) and regimen-related toxicity. We report on a 12-year-old girl with FA, who was treated by T-cell-depleted (TCD) peripheral blood HSCT from her haploidentical uncle, using a novel fludarabine-based preparative regimen without radiation. She had rapid engraftment with no toxicity and no GVHD. Progressive recovery of both numbers of lymphocyte and of proliferative response to polyclonal activators occurred over time. At 18 months after transplantation, she is well with 100% donor chimerism and has recovered normal immune function.

Child↗

34BetaE12 expression along the whole spectrum of neuroendocrine proliferations of the lung, from neuroendocrine cell hyperplasia to small cell carcinoma.

AIMS: Monoclonal antibody 34betaE12 (Ck34betaE12) recognizes a set of cytokeratins (1, 5, 10, 14) expressed in normal stratified squamous epithelium. We have recently reported its expression in squamous cell carcinoma and basaloid carcinoma, in contrast to large cell neuroendocrine carcinoma, an entity with overlapping morphological features with basaloid carcinoma. We have now examined the role of Ck34betaE12 in discriminating between neuroendocrine and non-neuroendocrine proliferations. METHODS AND RESULTS: We performed an immunohistochemical study of 228 cases, comprising the whole spectrum of lung neuroendocrine proliferations and tumours. All cases of neuroendocrine cell hyperplasia (n = 15), tumorlet (n = 23), typical carcinoid (n = 27) and atypical carcinoid (n = 23) were completely negative for Ck34betaE12. Although the neuroendocrine cells of small cell lung carcinoma and large cell neuroendocrine carcinoma were consistently negative, a strong and diffuse positive staining was found in the non-neuroendocrine components of combined small cell carcinoma (three of eight cases) and combined large cell neuroendocrine carcinoma (11 of 12 cases). In addition, scattered Ck34betaE12+ cells were noted in 11 of 64 (17%) large cell neuroendocrine carcinoma and in seven of 56 (12.5%) small cell carcinoma, which were not obviously histologically combined. This heterogeneity of high-grade neuroendocrine tumours was not observed in carcinoids which lack Ck34betaE12 clusters of reactive cells. There was mutual exclusion between expression of neuroendocrine markers and that of Ck34betaE12. CONCLUSION: We conclude that 34betaE12 expression excludes the neuroendocrine nature of tumour cells and uncovers the real frequency of combined forms in high-grade neuroendocrine tumours.

Biomarkers, Tumor↗

Evaluation of quinacrine treatment for prion diseases.

Based on in vitro observations in scrapie-infected neuroblastoma cells, quinacrine has recently been proposed as a treatment for Creutzfeldt-Jakob disease (CJD), including a new variant CJD which is linked to contamination of food by the bovine spongiform encephalopathy (BSE) agent. The present study investigated possible mechanisms of action of quinacrine on prions. The ability of quinacrine to interact with and to reduce the protease resistance of PrP peptide aggregates and PrPres of human and animal origin were analyzed, together with its ability to inhibit the in vitro conversion of the normal prion protein (PrPc) to the abnormal form (PrPres). Furthermore, the efficiencies of quinacrine and chlorpromazine, another tricyclic compound, were examined in different in vitro models and in an experimental murine model of BSE. Quinacrine efficiently hampered de novo generation of fibrillogenic prion protein and PrPres accumulation in ScN2a cells. However, it was unable to affect the protease resistance of preexisting PrP fibrils and PrPres from brain homogenates, and a "curing" effect was obtained in ScGT1 cells only after lengthy treatment. In vivo, no detectable effect was observed in the animal model used, consistent with other recent studies and preliminary observations in humans. Despite its ability to cross the blood-brain barrier, the use of quinacrine for the treatment of CJD is questionable, at least as a monotherapy. The multistep experimental approach employed here could be used to test new therapeutic regimes before their use in human trials.

Animals↗

Fungus colonisation of pulmonary rheumatoid nodule.

This report describes a 69 year old woman, suffering from active rheumatoid arthritis since the age of 60 and presenting with severe dyspnoea and cough. A computed tomography scan of the chest showed multiple bilateral pulmonary nodules, sometimes cavitated, associated with reticular opacities and pleural effusion. A videothoracoscopic excision of a cavitated nodule was performed. Seven days after surgery, a right pneumothorax developed, and the patient died of septicaemia one month later. Microscopically, the excised nodule was composed of necrotic fibrinoid material with a peripheral rim of palisaded histiocytes, extending to the pleural surface and containing several fungal hyphae morphologically consistent with aspergillus. A diagnosis of pulmonary rheumatoid nodule with fungus colonisation was made. In the lung, fungus colonisation is a rare complication of rheumatoid nodules. The most important differential diagnostic considerations are briefly discussed.

Aged↗

Investigating the dose-response relation between air pollution and total mortality in the APHEA-2 multicity project.

BACKGROUND: Several recent studies have reported significant health effects of air pollution even at low levels of air pollutants, but in most of these studies linear non-threshold relations were assumed. AIMS: To investigate the NO2 mortality dose-response association in nine cities participating in the APHEA-2 project using two different methods: the meta-smooth and the cubic spline method. METHODS: The meta-smooth method developed by Schwartz and Zanobetti is based on combining individual city non-parametric smooth curves; the cubic spline method developed within the APHEA-2 project combines individual city estimates of cubic spline shaped dose-response relations. The meta-smooth method is easier and faster to implement, but the cubic spline method is more flexible for further investigation of possible heterogeneity in the dose-response curves among cities. RESULTS: In the range of the pollutant common to all cities the two methods gave similar and comparable curves. Using the cubic spline method it was found that smoking prevalence acts as an effect modifier with larger NO2 effects on mortality at lower smoking prevalence. CONCLUSIONS: The NO2-mortality association in the cities included in the present analysis, could be adequately estimated using the linear model. However, investigation of the city specific dose-response curves should precede the application of linear models.

Air Pollutants↗

Behavior of SaOS-2 cells cultured on different titanium surfaces.

Surface properties may affect the clinical outcome of titanium dental implants. The aim of the present study was to investigate the effects of 3 different titanium surfaces-smooth (S), sandblasted (SB), and titanium plasma-sprayed (TPS)-on proliferation, differentiation, and apoptosis of human osteoblast-like cells, SaOS-2. Cell proliferation was significantly (p < 0.05) higher on the S surface, and synthesis of extracellular matrix proteins was more abundant on TPS and SB than on S surfaces. Analysis of integrin receptors showed a higher expression of alpha2, alpha5, alphaVbeta3, and ss1 on TPS as compared with SB and S surfaces. An increase in alkaline phosphatase activity was detected only on SB and TPS surfaces. Analysis of cell apoptosis did not demonstrate any significant difference among the 3 different surfaces. The results indicate that titanium surface topography affects proliferation and differentiation of osteoblast-like SaOS-2 cells, suggesting that surface properties might be important for bone response around dental implants in vivo.

Alkaline Phosphatase↗

Association of Maedi Visna virus with Brucella ovis infection in rams.

Maedi Visna Virus (MVV) is the etiological agent of a systemic disease of sheep, which causes lesions in lungs, the central nervous system, joints, and mammary glands. It has been speculated that the association with Brucella ovis may lead to the venereal shedding of the virus. In this work, samples of epididymis from ten rams positive for MVV and infected experimentally with Brucella ovis, were subjected to liquid-phase PCR, immunohistochemistry (IHC) and in situ PCR tests, aimed at identifying the pathogens in a tissue context. IHC was carried out using a monoclonal antibody raised against p28 MVV protein and a polyclonal antibody to B. ovis. Liquid phase- and in situ PCR were designed to amplify a portion of MVV proviral DNA Pol sequence. In the animals showing B. ovis-related histopathological changes, IHC clearly demonstrated a positivity for B. ovis and MVV in interstitial and epithelial ductal cells. In situ PCR assessed the presence of MVV proviral DNA in macrophages and elements inside the epithelium. The unaffected and reagent control samples constantly gave negative results. Taken together, these data demonstrate that MVV may affect ovine epididymis, apparently taking advantage of the concurrent infection by B. ovis. The tropism of MVV for the epididymal epithelial cells, may be responsible for its excretion with the semen.

Animals↗

[Round atelectasis of the lung: clinicopathological study of 6 cases and review of the literature].

OBJECTIVE: To report about 6 new patients with round atelectasis of the lung, 1 of them professionally exposed to asbestos and another to silicates. RESULTS: The patients, 5 males and 1 female, presented with a peripheral, rounded pulmonary opacity, simulating a neoplasm. The examination of the surgical specimen revealed a pleuritis, with multiple pleural folding: the underlying lung parenchima was compressed, but otherwise unremarkable. CONCLUSIONS: Round atelectasis is relatively unusual for the pathologist. However, the correct diagnosis is potentially important, because the lesion can be the sign of a significant asbestos exposure.

Adenocarcinoma↗

[Primary leiomyoma of the lung, with clear-cell features and admixed alveolar spaces: description of a case presenting with pneumothorax].

OBJECTIVE: To report about a primary leiomyoma of the lung, with clear cell features and with admixed alveolar epithelium. RESULTS AND CONCLUSIONS: The patient, a 18-year-old female, non smoker, presented with a well-delimited pleuro-pulmonary mass, 6,5 cm across, located in the right upper lobe. The mass was discovered 5 years previously, following an episode of spontaneous pneumothorax; initially interpreted as an intralobar pulmonary sequestration, it was subsequently removed due to a small dimensional increase. A gynaecological examination, a thoracic CT-scan obtained 2 years after operation, and a recent abdomino-pelvic echography were negative. The patient is alive and well 7 years after surgery. Microscopically, the lesion was well delimited and it was punctuated by multiple cysts of variable dimensions, covered by bland cubic cells. The solid part of the lesion was composed by oval, clear cells, merging with fusiform elements with densely eosinophilic cytoplasm. Significant atypia, mitoses and necrosis were absent. Immunohistochemically, both oval and spindle cells were strongly positive for vimentin, smooth muscle actin, desmin and h-caldesmon, negative for cytokeratin, EMA, CD-34, CD-10, CD-117, HMB-45, TTF-1, BCL-2, GFAP, calretinin, chromogranin, estrogen and progesterone receptors. Cells covering the cystic spaces were positive for cytokeratin, TTF-1 and EMA, negative for all the other antibodies tested. Smooth muscle proliferations of the lung are briefly discussed, together with the most important problems in differential diagnosis.

Adolescent↗

[Solitary fibrous pseudopapillary tumor of the lung: pulmonary fibroadenoma and adenofibroma revisited].

We describe a peculiar pulmonary lesion, that we interpreted as a pseudopapillary variant of solitary fibrous tumor. The patient was a 62-year-old asymptomatic male, non smoking, presenting with a peripheral nodule, 0.8 cm across, located in the lower lobe of the right lung. The patient is alive and well 18 months after surgical excision of the nodule. Microscopically, the lesion was well-circumscribed and characterized by a diffuse pseudopapillary pattern. Pseudopapillae were large, and were covered by a rim of cubic epithelium devoid of atypia. The stromal axis was fibrous and contained scattered bland spindle cells. Immunohistochemically, the latter were strongly positive for vimentin and CD34, focally positive for BCL2 and CD99, negative for cytokeratin, EMA, TTF1, calretinin, smooth muscle actin, desmin and S100 protein; the epithelial cells were immunoreactive for cytokeratin, EMA and TTF1. We interpret this lesion as a peculiar pseudopapillary variant of solitary fibrous tumor, corresponding to what has been reported in the literature as pulmonary adenofibroma and fibroadenoma. The most important differential diagnostic considerations are briefly discussed.

Adenofibroma↗

[Enterocolic phlebitis. Description of a case and review of the literature].

OBJECTIVE: To report about a case of enterocolic phlebitis, a rare cause of ischemic intestinal necrosis. RESULTS AND CONCLUSIONS: The patient, a 71 year-old male, presented with signs of acute abdomen. A right hemicolectomy was performed, which revealed a tubulovillous adenoma with high grade dysplasia located in the ascending colon, and a diffuse ischemic colitis. A localized lymphocytic and granulomatous phlebitis was present in the resected colon. The arteries were spared by the inflammatory process. The patient is alive and well 7 years after surgery. The literature concerning enterocolic phlebitis, a peculiar form of localized intestinal vasculitis, is briefly summarized.

Abdomen, Acute↗

Experimental Maedi Visna Virus Infection in sheep: a morphological, immunohistochemical and PCR study after three years of infection.

A morphological, immunohistochemical and polymerase chain reaction (PCR) study was performed on eight ewes experimentally infected with an Italian strain of Maedi-Visna Virus (MVV) in order to evaluate the lesions and the viral distribution after three years of infection. At the moment of euthanasia, seven sheep were seropositive for MVV, while one sheep in poor body conditions was seronegative since one year. Lungs, pulmonary lymph nodes, udder, supramammary lymph nodes, carpal joints, the CNS, spleen and bone marrow of the eight infected sheep were collected for histology, for immunohistochemical detection of the MVV core protein p28 and for PCR amplification of a 218 bp viral DNA sequence of the pol region. The most common histological findings consisted of interstitial lymphoproliferative pneumonia and lymphoproliferative mastitis of different severity, while no lesions were observed in the CNS. MVV p28 antigen was immunohistochemically labelled in lungs, udder, pulmonary lymph nodes, spleen and bone marrow but not in the CNS of all the eight infected sheep. A 218 bp sequence of MVV pol region was detected in lung of a seropositive and of the seroconverted negative sheep. The results suggest that (i) MVV causes heterogeneous lesions in homogeneously reared ewes, (ii) MVV p28 antigen is detectable not only in inflammed target organs, but also in pulmonary lymph nodes, spleen and bone marrow, and (iii) immunohistochemistry and PCR are useful methods for Maedi-Visna diagnosis in suspected cases, also when serological tests are negative.

Animals↗

Adrenomedullin and endocrine disorders.

Adrenomedullin (AM) is a recently discovered potent vasodilatory peptide, originally isolated in extracts of human pheochromocytoma, with activities including maintenance of cardiovascular and renal homeostasis through vasodilatation, diuresis and natriuresis. Human AM consists of 52 amino acids with a 6-member ring structure linked by a disulfide bond and amidated COOH terminal, which belongs to calcitonin gene-related peptide (CGRP) and amylin. The main sites of AM production are the lungs, vascular tissues (both endothelial and smooth muscle cells), heart, kidney, adrenal glands, pancreatic islets, placenta, anterior pituitary gland and gastrointestinal neuroendocrine system. Intravenous injection of AM increases blood flow predominantly in the tissues with the highest AM expression, suggesting that AM functions primarily as a paracrine/autocrine hormone, but it is also important as circulating hormone. The objective of this review is to analyze the evidence that AM may play a role in some endocrine disorders.

Adrenal Insufficiency↗