89 results on '"L. Montemurro"'
Search Results
2. Bile duct injuries during laparoscopic cholecystectomy: a 1994–2001 audit on 13,718 operations in the area of Rome
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C. De Stefano, Gianfranco Silecchia, E. Nanni, Francesco Gossetti, M. Di Paola, G. Montalto, L. Alessandroni, F. Cristini, A. Gatto, M. Valle, B. Benini, Riccardo Angeloni, D. Polito, E. Puce, A. Terenzi, A. Dalla Torre, S. Manfroni, L. Montemurro, P. Mascagni, Sandro de Vita, Paolo Gentileschi, Luigi Masoni, T. Zanarini, Massimo Carlini, E. Santoro, and Marco Catarci
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Rome ,cholecystectomy ,laparoscopic/adverse effects ,bile duct/injuries ,multicenter studies ,Aged ,Bile Ducts ,Cholecystectomy ,Cholecystectomy, Laparoscopic ,Cholelithiasis ,Female ,Follow-Up Studies ,Humans ,Incidence ,Intraoperative Complications ,Jejunum ,Liver ,Medical Audit ,Middle Aged ,Prospective Studies ,Retrospective Studies ,Surveys and Questionnaires ,Laparoscopic ,Medicine ,Laparoscopy ,medicine.diagnostic_test ,business.industry ,Bile duct ,General surgery ,Gallbladder ,Incidence (epidemiology) ,Retrospective cohort study ,Settore MED/18 ,Surgery ,medicine.anatomical_structure ,Biliary tract ,business ,Abdominal surgery - Abstract
Bile duct injuries (BDIs) during laparoscopic cholecystectomy (LC) still are reported with greater frequency than during open cholecystectomy (OC). In 1999, a retrospective study evaluating the incidence of BDIs during LC in the area of Rome from 1994 to 1998 (group A) was performed. In addition, a prospective audit was started, ending in December 2001 (group B). In group A, 6,419 LCs were performed (222 were converted to OC; 3.4%). In group B, 7,299 LCs were performed (225 were converted to OC; 3.1%). Seventeen BDIs (0.26%) occurred in group A and 16 (0.22%) in group B. Overall, mortality and major morbidity rates were 12.1% and 30.3%, respectively, without significant differences between the two groups. The incidence and clinical relevance of BDIs during LC in the area of Rome appeared to be stable over the past 8 years and were not influenced by the use of a prospective audit, as compared with a retrospective survey.
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- 2003
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3. ACLIMATACIÓN AL ESTRÉS HÍDRICO DE PLANTAS DE UVA DE MESA cv. CRIMSON SEEDLESS CULTIVADAS EN MACETA
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Rafael Domingo, L. Montemurro, J.M. de la Rosa, M. García, María R. Conesa, and Alejandro Pérez-Pastor
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Congreso Nacional de Riegos - Abstract
1- Introduccion. Objetivo del trabajo Numerosas investigaciones han resaltado la importancia que ejerce el nivel de estres hidrico en la hoja sobre las propiedades estructurales y de los intercambios gaseosos de la vid (Chaves et al. 2010; Romero et al. 2014). Sin embargo, en uva de mesa, no se ha documentado el impacto que ejerce en estos intercambios la aclimatacion de las plantas al deficit hidrico. El objetivo de este trabajo fue comprobar, la capacidad de adaptacion (endurecimiento) y tolerancia a la sequia de la uva de mesa ante diferentes condiciones de estres hidrico. 2- Descripcion del tema y del proceso de ejecucion El ensayo bajo invernadero se realizo en la Estacion Experimental Agroalimentaria ‘Tomas Ferro’ de la ETSIA-UPCT, situada en la Palma, (Murcia), durante el verano de 2014. Los plantones de uva de mesa cv. Crimson Seedless fueron injertados en vivero sobre patron Paulsen 1103 y trasplantados a macetas de 5 litros sobre sustrato de fibra de coco. Se seleccionaron 9 plantas por tratamiento de similar desarrollo y aspecto (75 cm de altura y 1 cm de diametro de tronco). El sistema radicular de todas las plantas se dividio en dos mitades (cada mitad en una maceta), a fin de mantener similares condiciones experimentales. La radiacion fotosinteticamente activa, temperatura del aire y humedad relativa (RFA, T a y HR) fueron registradas en una estacion climatica instalada dentro del invernadero. A partir de T a y HR se calculo el DPV. El sistema de riego consistio en una hilera de plantas con un emisor por maceta de 2 L h -1 (2 emisores planta -1 ). Todas las plantas se regaron diariamente durante 30 dias con identicas dosis de agua y solucion nutritiva vegetativa. Posteriormente, se establecieron 5 tratamientos de riego de acuerdo a un diseno experimental al azar de 3 repeticiones por tratamiento: (i) CTL-1 y CTL-2, ambos regados diariamente a condiciones de humedad de suelo correspondiente a capacidad de campo (Ө CC ≈ 28%); (ii) Riego deficitario (RD), dosis equivalente al 50% del CTL-1; (iii) Riego fijo por desecacion parcial de raices (PRD FIX ), dosis equivalente al 50% del CTL-1, aplicado en una mitad de raices de forma fija; (iv) Riego alterno por desecacion parcial de raices (PRD ALT ), dosis equivalente al 50% del CTL-1, aplicado en una solo mitad de raices de forma alterna, cuando el contenido de agua en el suelo (Ө v ) de la maceta sin riego se reducia al 12% (correspondiente al punto de marchitez). Estos tratamientos se aplicaron durante 1 mes (periodo de endurecimiento ) e inmediatamente despues, se suprimio el riego en todos los tratamientos durante 7 dias ( periodo de estres ), a excepcion del tratamiento CTL-1, que se mantuvo regado en las condiciones iniciales. Finalizado el periodo de estres, todas las plantas fueron tratadas como las plantas CTL-1, con riego diario ( periodo de recuperacion ). Se realizaron las siguientes determinaciones: potencial hidrico de tallo a mediodia (Ψ t,md ) y potencial hidrico antes del alba (Ψ pd ) con camara de presion; contenido volumetrico de agua en el suelo (Ө v ) con sondas GS3; asimilacion neta de CO 2 , (A lm ) conductancia estomatica (g sm ) y eficiencia de uso del agua (EUA, g CO 2 /g H 2 O transpirada) con un medidor portatil CIRAS-2 en condiciones de saturacion; temperatura del dosel vegetal (T f, oC) con una pistola de infrarrojos digital. A partir de los valores de T f y T a , se calculo el indice de estres hidrico (CWSI, Idso et al., 1981). Ademas, al final del periodo de estres, se evaluo la calidad visual de las plantas estableciendo 4 categorias expresadas en porcentaje: (1) plantas en condiciones ideales; (2) plantas en condiciones aceptables; (3) plantas con danos moderados; (4) plantas con danos severos. Para el analisis de los datos se realizo un ANOVA simple y test de rango multiple de Duncan (P
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- 2015
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4. Nephrolithiasis as a presenting feature of chronic sarcoidosis
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G Rizzato, L Montemurro, and P Fraioli
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Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Systemic disease ,Pediatrics ,Time Factors ,Sarcoidosis ,Population ,urologic and male genital diseases ,Kidney Calculi ,Adrenal Cortex Hormones ,Recurrence ,medicine ,Humans ,Hypercalciuria ,education ,Calculus (medicine) ,Retrospective Studies ,education.field_of_study ,business.industry ,Incidence ,Incidence (epidemiology) ,Retrospective cohort study ,Middle Aged ,medicine.disease ,female genital diseases and pregnancy complications ,Surgery ,Chronic Disease ,Female ,business ,Complication ,Research Article - Abstract
BACKGROUND--Renal calculi have been reported to occur in about 10% of patients with chronic sarcoidosis, but nephrolithiasis as a presentation of this disease has not been studied. METHODS--The charts of 618 patients with histologically proven sarcoidosis, seen in the period October 1978-1992, were reviewed in order to identify nephrolithiasis at presentation. RESULTS--Seventeen patients had renal calculi which preceded other manifestations of sarcoidosis. In six the occurrence of calculi suggested the diagnosis. Another eight patients had a previous history of recurrent colic with calculi. The time intervals between the first calculus and the appearance of other manifestations of sarcoidosis ranged from one to 25 years, but it was over four years in only two cases and all had at least one calculus in the year before the diagnosis was made. In the other three patients appearance of the calculus was distant in time and was probably unrelated to their sarcoidosis. In most cases the sarcoidosis was chronic and needed long term treatment with corticosteroids. Four patients had further calculi during follow up (one month to 16 years) due to an improper withdrawal of treatment decided by the patient in two cases, and to the reduction in the corticosteroid dose in the other two. CONCLUSIONS--Calculi were the presenting feature of sarcoidosis in six (1%) patients, and were the first manifestation of the disease in a total of 14 (2.2%). This frequency is over 20 times the likely incidence of calculi in the general population. Renal calculi may therefore be a rare primary manifestation of sarcoidosis. In such cases the disease is likely to be chronic and to require long term corticosteroid therapy. Sarcoidosis should always be suspected in cases of nephrolithiasis of unknown origin.
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- 1995
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5. Comparative study of protirelin tartrate and standard therapy in the treatment of stroke patients
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Patrizia Fraioli, Gianfranco Rizzato, Guido Montanari, and L. Montemurro
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Pharmacology ,Chemotherapy ,medicine.medical_specialty ,Activities of daily living ,business.industry ,medicine.medical_treatment ,medicine.disease ,Surgery ,Clinical trial ,Tolerability ,Rating scale ,Anesthesia ,Statistical significance ,medicine ,Pharmacology (medical) ,Protirelin ,business ,Stroke - Abstract
We conducted a clinical trial to evaluate the effects of protirelin tartrate on the overtone, mobility, activities of daily living, and degree of disability of 60 patients who experienced a cerebral stroke within the 15 days preceding the start of therapy. This open, controlled study compared patients treated with protirelin plus standard therapy with those receiving standard therapy alone. The standard therapy consisted of cerebral antiedemic drugs and antiaggregants. During the first month, protirelin was administered intravenously in the hospital at a dose of 2 mg twice daily for 15 days, followed by a 15-day washout period. From month 2 through month 6, an additional five cycles of protirelin therapy given intramuscularly were administered at home. In both the protirelin and standard therapy groups, a substantial improvement was observed compared with the patients' clinical condition at baseline. This improvement was more significant in the group treated with protirelin. In particular, the difference between the protirelin and standard therapy groups for the degree of autonomy (as measured by using the Modified Parkside Behavior Rating Scale) and for mobility (as measured by using Albert's scale) reached statistical significance after 6 months of treatment. This trend was confirmed by the subjective evaluations after 3 months: most patients treated with protirelin improved, while most patients receiving standard therapy remained stable. Data on tolerability revealed no clinically significant differences between the two groups at any observation time.
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- 1994
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6. Meropenem versus imipenem: Relationship between microbiological parameters and clinical outcome in lower respiratory tract infections
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E. Magliano, L. Montemurro, L. Cava, Guido Montanari, Patrizia Fraioli, D. Fanti, and Gianfranco Rizzato
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Pharmacology ,Chronic bronchitis ,Pathology ,medicine.medical_specialty ,Imipenem ,biology ,Cilastatin ,business.industry ,Klebsiella pneumoniae ,medicine.disease_cause ,biology.organism_classification ,Meropenem ,Microbiology ,Haemophilus influenzae ,Moraxella catarrhalis ,medicine ,Pharmacology (medical) ,business ,Antibacterial agent ,medicine.drug - Abstract
Thirty-two patients with lower respiratory tract infections (18 with pneumonia, 14 with exacerbation of chronic bronchitis) were treated intramuscularly with either meropenem (MEM group) 500 mg twice daily (BID) (n = 16) or a combination of 500 mg of imipenem and 500 mg of cilastatin (IMI group) BID (n = 16), according to a randomized, open, clinical, and microbiological study. The clinical results (5 failures in the IMI group—3 of 10 from pneumonia, 2 of 6 from exacerbation of chronic bronchitis; 2 superinfections in the IMI group; 1 relapse of bacterial bronchitis in the MEM group) are part of a multicenter study, which will be published elsewhere in detail with safety and tolerance results. The aim of this study was to evaluate the relationship between microbiological parameters (isolates, zone diameters, minimum inhibitory concentrations [MICs], beta-lactamases, killing rates) and the clinical outcome. Thirteen pathogens (sputum culture if acceptable on Bartlett criteria, bacterial count ≥ 10 6 CFU/ml) were isolated in the MEM group from 10 different patients (3 of them with 2 isolates each); 13 pathogens were also isolated in the IMI group from 7 different patients (1 with 4 isolates, 1 with 3 isolates, and 2 with 2 isolates). Beta-lactamases (nitrocefin) were found in 3 isolates from 3 different patients in the MEM group (all with good outcome, confirming no difference in the results for MEM between beta-lactamase and non-beta-lactamase producing strains), and in 7 isolates from 3 patients in the IMI group; in 2 of them imipenemcilastatin failed. One had beta-lactamase producing Pseudomonas aeruginosa and Staphylococcus aureus exacerbation, the other one had beta-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis pneumonia. Both MEM and IMI zone diameter was Xantomonas maltophilia , one S aureus ); both were allocated to imipenem-cilastatin, which failed. MICs could be studied in 19 isolates; in all MEM-MIC was ≤0.25 μg/ml and IMI-MIC was >0.25 μg/ml. IMI-MIC was ≥ 4 μg/ml in 7 isolates from 6 different patients, 3 of them treated with imipenem-cilastatin, which failed in 2: 1 with beta-lactamase producing H influenzae pneumonia (IMI-MIC 8 μg/ml, MEM-MIC 0.12 μ/ml), 1 with exacerbation of chronic bronchitis due to H influenzae (IMI-MIC 4 μg/ml, MEM-MIC 0.12 μg/ml); the IMI zone diameter was >18 mm in all of the above 7 isolates, so that it appeared to be unreliable for evaluating IMI resistance. The MEM zone diameter-MIC plot does not show a correlation, probably because all MEM-MICs fall in the nonlinear portion of the regression line on the scattergram. Moreover, in six Enterobacteriaceae isolates MEM and IMI killing rates were studied at 1 × MIC, 2 × MIC, 4 × MIC, and 8 × MIC; in each instance there was a 2 log 10 or greater decrease in viability (in CFU/ml) within 6 hours of exposure to MEM (but not to IMI). The MEM killing rate was far better than the IMI killing rate versus Citrobacter freundii and versus Klebsiella pneumoniae , and better versus Klebsiella oxytoca , whereas results were similar versus Enterobacter cloacae . In conclusion, in vitro microbiological parameters reflected accurately (with some exclusion of IMI zone diameter) the clinical outcome, and meropenem compared favorably versus imipenem both in vitro and in vivo. Local tolerance and safety results were very similar for imipenem-cilastatin and meropenem; both regimens were well tolerated.
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- 1993
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7. Reversibility of exogenous corticosteroid-induced bone loss
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G Rizzato and L Montemurro
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Pulmonary and Respiratory Medicine - Abstract
Osteoporosis is not usually considered to be reversible, as it is a consequence of the ageing process. However, an improvement of bone mineral density after successful surgery in Cushing's syndrome has been shown in several reports. The question of reversibility of exogenous corticosteroid-induced osteoporosis is, as yet, unanswered, possibly because of the difficulty in discontinuing steroids after long-term use. We describe six patients, all under 45 yrs of age, with chronic long-standing sarcoidosis, in whom long-term prednisone therapy resulted in 15 +/- 7% bone loss, as evaluated by quantitative computed tomography. This side-effect appeared fully reversible after prednisone withdrawal. This report of the reversibility of exogenous corticosteroid-induced bone loss needs confirmation in elderly people, where the capacity for recovery of bone mass could be reduced. Such potential for recovery may have implications for the pattern of use of corticosteroids.
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- 1993
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8. Bone Mineral Content in Sarcoidosis
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Patrizia Fraioli, L. Montemurro, and Gianfranco Rizzato
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Pulmonary and Respiratory Medicine ,Systemic disease ,Pathology ,medicine.medical_specialty ,business.industry ,Toxicity ,Medicine ,Bone mineral content ,Sarcoidosis ,Critical Care and Intensive Care Medicine ,business ,medicine.disease - Published
- 1992
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9. Prevention of corticosteroid-induced osteoporosis with salmon calcitonin in sarcoid patients
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Gianfranco Rizzato, Gianpiero Tosi, Patricia Fraioli, Gianfranco Schiraldi, Angelo Riboldi, and L. Montemurro
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Adult ,Calcitonin ,Male ,medicine.medical_specialty ,Sarcoidosis ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Osteoporosis ,Injections, Intramuscular ,Gastroenterology ,Endocrinology ,Bone Density ,immune system diseases ,Prednisone ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Orthopedics and Sports Medicine ,Quantitative computed tomography ,Administration, Intranasal ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Surgery ,surgical procedures, operative ,Nasal spray ,Orthopedic surgery ,Corticosteroid ,Female ,business ,therapeutics ,human activities ,Follow-Up Studies ,medicine.drug - Abstract
The aim of this study was to evaluate the usefulness of salmon calcitonin (sCT) in preventing corticosteroid-induced osteoporosis. Three groups of patients with sarcoidosis requiring long-term steroid therapy were followed for 2 years with yearly evaluations of vertebral cancellous mineral content (VCMC) by quantitative computed tomography. The first group (n = 18) was treated with intramuscular (i.m.) sCT for the 2-year study period; the second (n = 11) with i.m. sCT for the first 4 months and then with sCT nasal spray for 20 months; the third (n = 35) received no sCT. We observed a large mineral loss in the third group but a very slight drop of VCMC in the two groups receiving sCT. SCT nasal spray was better tolerated and as effective as i.m. injections. The action of sCT appeared extremely useful, especially in the first year of steroid therapy when corticosteroid-induced mineral loss was maximal. We conclude that sCT nasal spray is a good tool for preventing corticosteroid-induced osteoporosis.
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- 1991
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10. [Gastric hemangiopericytoma: unusual neoplasia but not always benign]
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L, Montemurro, M, Catarci, A, Bellotti, R, Piccirillo, B, Battaglia, M A, Viarengo, L, Ricca, and G B, Grassi
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Adult ,Male ,Stomach Neoplasms ,Humans ,Hemangiopericytoma - Published
- 2006
11. [Metastatic malignant melanoma of the pancreas: which strategy?]
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L, Montemurro, M, Catarci, S, Mancini, A, Bellotti, R, Piccirillo, B, Battaglia, M A, Viarengo, L, Ricca, and G B, Grassi
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Male ,Pancreatic Neoplasms ,Humans ,Middle Aged ,Melanoma - Published
- 2006
12. Comparison among ecography, scintigraphy and surgery in the localization of parathyroid glands in uremic patients undergoing parathyroidectomy
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S, Mazzaferro, G, Matera, G, Barresi, E, Mancini, C, Conte, G, Otranto, F, Taggi, S, Gallina, F, Gossetti, L, Montemurro, D, Proposito, and M, Carboni
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Adult ,Male ,Parathyroidectomy ,Technetium Tc 99m Sestamibi ,Time Factors ,Middle Aged ,Parathyroid Glands ,Data Interpretation, Statistical ,Humans ,Female ,Hyperparathyroidism, Secondary ,Radionuclide Imaging ,Follow-Up Studies ,Sodium Pertechnetate Tc 99m ,Ultrasonography ,Uremia - Abstract
Sensitivity and specificity of the most widely employed techniques of parathyroid glands localization, namely echography and scintigraphy, are mostly obtained with short-term follow-up data and do not underline the existence of a methodological problem. As a matter of fact, both methods identify only pathological glands, with no "normal" results; therefore "true negatives" cannot be obtained. Aim of our study was to compare, by means of a statistically appropriate approach, the results of echography, scintigraphy and surgery with the data obtained after a mid term follow-up period, enabling us to discover all parathyroid glands.Twenty six consecutive dialysis patients (14M/12F; age 50+/-12 years) underwent echography and scintigraphy immediately before a total parathyroidectomy with autotransplantation and were followed-up for 6 months to recognize all the existing glands (PTH levels and scintigraphy).Total identified glands were: 73 by scintigraphy, 86 by echography, 99 by surgery and 103 by follow-up data. The concordance indexes (K0) between the number of glands effectively present in the individual patient (follow-up data) and those identified with each method were rather low with scintigraphy (0.071) and echography (0.218), and acceptable (0.578) with surgery. The number of patients correctly classified was: 9/26 (34,6%) with scintigraphy, 13/26 (50%) with echography and 22/26 (85%) with surgery. Finally, the number of wrongly identified glands (from zero to three) in each patient was similar with scintigraphy (65,4%) and echography (50%) and significantly better with surgery (15,6%; p0.01).The most reliable technique to identify parathyroid glands in uremic subjects is surgery, nonetheless a meticulous clinical follow-up is necessary to recognize all of them.
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- 2006
13. [Lymphangiomatosis of the spleen. Report of a clinical case]
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C, Talarico, V, Cerasoli, B, Mancini, G, Mulieri, F, Cancellario D'Alena, L, Montemurro, and F, Verna
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Cysts ,Humans ,Female ,Middle Aged ,Splenic Diseases - Abstract
Lymphangiomatosis confined to the spleen is a very are condition. The authors in this article describes one new case and briefly reviews the literature. In this case, after the exclusion of an hydatidosis of the spleen, a total splenectomy was performed. The histologic findings confirmed the lymphangiomatosis of the spleen. The authors emphasize the surgical strategy in splenic lymphangiomyomatosis, infact the total splenectomy is mandatory, because the splenic parenchyma is nearly completely substitute by the cysts. For this reason is preferably, before surgery, to perform the antibateric profilaxis against the OPSI.
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- 2001
14. [A case of intestinal occlusion caused by endometriosis of the cecum]
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M, Veneziano, F, Zaraca, M, Framarino, M, Di Paola, M, Giobbe, L, Montemurro, C, Fabiani, P, Filippoussis, B, Mancicni, L, Marzetti, and M, Carboni
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Adult ,Endometriosis ,Cecal Diseases ,Humans ,Female ,Emergencies ,Intestinal Obstruction - Abstract
The purpose of this study is to heighten awareness of intestinal endometriosis, a disease that may mimic other abdominal pathologies (bowel carcinoma, intestinal inflammatory disease, diverticulitis), sometimes found in the emergency setting. The Authors report a case of acute bowel obstruction due to coecal endometriosis with appendix mucocele, peritoneal pseudomyxoma and ovarian endometrioma. The patient was operated on in the emergency setting, a right colectomy was performed and she then received pharmacological suppressive treatment with Gn-RH analogues and danatrol. We remark that preoperative diagnosis is very difficult in those cases that do not have a past history of pelvic endometriosis. An accurate anamnesis regarding the chronology of pain onset (typically only during the menstruation at first), but especially intraoperative histopathologic examination are useful for diagnosis. An increased awareness of intestinal endometriosis in reproductive age women with acute bowel obstruction, associated with an accurate anamnesis of menstrual history may allow pre- or intraoperative diagnosis, which is the clue to a less aggressive operation. Postoperative follow up and hormonal therapy are mandatory.
- Published
- 2000
15. The clinical spectrum of the sarcoid peripheral lymph node
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G, Rizzato and L, Montemurro
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Adult ,Male ,Time Factors ,Sarcoidosis ,Sarcoidosis, Pulmonary ,Biopsy ,Humans ,Female ,Lymph Nodes ,Lymphatic Diseases ,Follow-Up Studies ,Retrospective Studies - Abstract
The finding of sarcoid-type granulomas in a peripheral lymph node (PLN) without clinical evidence of changes suggestive of sarcoidosis elsewhere poses a diagnostic problem. The long term follow-up of these patients has never been described in adults. AIMS OF THE WORK: 1. To describe in the above population whether and when a definite diagnosis of sarcoidosis was eventually made, and the time required to make the diagnosis. 2. To study the percentage of peripheral lymph node presentation in sarcoidosis.A peripheral lymph node presentation, with lymph node biopsy demonstrating sarcoid granulomas, was seen in 127 patients over the last 20 years. Detailed investigation permitted the early diagnosis of sarcoidosis in 76, and of sarcoid reaction in 8 patients. The other 43-patients with granulomatous lymph node and no clinical evidence of changes outside the lymphatic system at the onset are the subject of the present study.Periodic examination at our Sarcoid Clinic every 2 to 4 months, in a long term median follow-up of 36 months (range 1 to 203) and workup according to clinical need, including chest X ray and Computed Axial Tomography (CAT), pulmonary function tests, total body 67Ga scan, Broncho Alveolar Lavage (BAL) studies, blood cell counts, 24 h calciuria and urine analysis, serological tests for liver function, calcaemia, Angiotensin Converting Enzyme (ACE).The diagnosis of sarcoidosis (chronic in all) could be made in 33 patients (25 pulmonary, 8 extrapulmonary), after a median time from presentation of 5 years (range 3-288 months). In the other 10, in spite of a median duration of the illness of 62 months (range 20-487), our diagnosis has been idiopathic granulomatous disease of peripheral lymph nodes. Thus, we observed 109 patients in 20 years presenting with lymph nodes that were surgically removed and provided the diagnosis of sarcoidosis sooner (76 patients) or later (33 patients).1. In patients presenting only sarcoid granulomas in peripheral lymph nodes, sarcoidosis may be diagnosed months or years later, but a subpopulation of them still exists where granulomatous lesions remain unexplained. 2. In our series of patients, peripheral lymph node presentation occurred in 11.7% of cases of sarcoidosis.
- Published
- 2000
16. [Routine use of open laparoscopy: technique and results in 1006 consecutive cases]
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M, Catarci, F, Zaraca, G, Mulieri, M, Di Paola, L, Montemurro, P, Filippoussis, E, Greco, F, Gossetti, and M, Carboni
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Adult ,Aged, 80 and over ,Male ,Spermatic Cord ,Adolescent ,Fundoplication ,Hernia, Inguinal ,Middle Aged ,Laparoscopes ,Meckel Diverticulum ,Cholecystectomy, Laparoscopic ,Appendectomy ,Humans ,Female ,Laparoscopy ,Pneumoperitoneum, Artificial ,Aged - Abstract
Blind insertion of the Veress needle and/or the first trocar is one of the most frequent causes of laparoscopic surgery complications. Nevertheless, the closed technique is still more preferred than the open one. The Authors retrospectively analyzed 1006 consecutive laparoscopic procedures in which Hasson's technique was routinely utilized. The overall complication rate was 2.2%, but the vast majority of complications occurred during the learning curve (6% vs. 1.9%). The Authors conclude that after the first 50 cases the open technique is a quick and safe procedure.
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- 1999
17. Acute biliary pancreatitis. Role of laparoscopy after 30 years of traditional surgery experience
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F, Zaraca, M, Di Paola, F, Gossetti, M, Catarci, P, Trentino, D, Proposito, P, Filippoussis, E, Talarico, V, Cerasoli, C, Talarico, L, Montemurro, and M, Carboni
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Adult ,Male ,Time Factors ,Cholecystectomy, Laparoscopic ,Pancreatitis ,Acute Disease ,Humans ,Female ,Gallstones ,Middle Aged ,Algorithms ,Aged - Abstract
The authors herein show their own experience in the treatment of acute biliary pancreatitis. Aim of this study is to evaluate the effectiveness and the safety of the "early" laparoscopic approach to the mild to moderate acute biliary pancreatitis. The authors studied sixty cases of laparoscopic cholecystectomy with intraoperative colangiography for acute biliary pancreatitis (M/F 1:1.2; mean age 59.6 yrs, range 29.79). The patients were divided in two groups on the basis of the severity of the pancreatitis, defined through Ranson's score and Balthazar classification. The mortality rate was nil. Intraoperative morbidity rate was 6.6% in the group I (3/45), and 13.3% in the group II (2/15). Postoperative morbidity rate was 6.7% (3/45) in the group I and 40% in the group II (6/15). The authors show an original diagnostic and therapeutic algorithm for the treatment of acute biliary pancreatitis. Early laparoscopic cholecystectomy with I.O.C. is proposed as the gold standard treatment for mild to moderate acute biliary pancreatitis. This approach appears to be effective and safe in their experience. In case of severe acute biliary pancreatitis, further investigations are mandatory to evaluate the role of laparoscopic approach.
- Published
- 1999
18. The late follow-up of chronic sarcoid patients previously treated with corticosteroids
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G, Rizzato, L, Montemurro, and P, Colombo
- Subjects
Adult ,Male ,Time Factors ,Sarcoidosis ,Logistic Models ,Sarcoidosis, Pulmonary ,Recurrence ,Retreatment ,Humans ,Prednisone ,Female ,Glucocorticoids ,Follow-Up Studies ,Retrospective Studies - Abstract
The aim of the study was to evaluate, in a white population with chronic sarcoidosis, the rate and pattern of relapses, the correlated factors, and the course of disease after prednisone withdrawal.We have retrospectively examined the charts of 702 consecutive patients with histologically proven sarcoidosis, first seen in the Milan Sarcoidosis Clinic in the period October 1978-October 1994. 239 patients required corticosteroid therapy; in 82 it was possible to discontinue prednisone therapy and to have a follow-up of at least 18 months after withdrawal.A relapse, requiring a new course of steroids, was observed in 30 (36.6%) of the 82 patients (R group). The other 52 patients (No-R group) did not relapse during a mean follow-up of 36.8 +/- 24.8 months (range 18-125). There were no relapses after 3 asymptomatic years of prednisone withdrawal. Extrapulmonary sarcoidosis was a reason for giving therapy in 46.6% of patients in the R group, vs 23.0% in the No-R group (P0.05). The first course of therapy lasted 22 months [median time; i.q. 11.5 to 34.5] in R group vs 26 months [i.q. 18 to 41] in No-R group (P0.05). The mean daily prednisone dose was higher in the R group: 17 mg [median value; i.q. 8.9 to 23.2] vs 10.6 mg [i.q. 8.1 to 13.8] in the No-R group (p0.05). Logistic regression confirmed the prognostic significance of mean daily prednisone dose and of extrapulmonary sarcoidosis at presentation (P0.01). A mild sarcoid activity at the time of withdrawal was still present in 51.9% of patients who did not relapse, and in 66.7% of patients who relapsed (p0.05). Relapse in the first year after withdrawal of prednisone therapy occurred in twenty-five of the 30 patients. The pattern of relapse was different from the initial manifestation in 5. Nine of the 30 patients could ultimately be weaned successfully from prednisone.Relapses occurred in 36.6% of cases, and their pattern was the same as the initial manifestation in the majority of cases. A mild sarcoid activity at the time of withdrawal is not a reason for continuing steroids when the disease is abating. In our white population severe irreversible pulmonary impairment is rare, and even patients requiring chronic therapy need low prednisone dosage, usually around 10 mg daily, to control the disease in the late course.
- Published
- 1998
19. Uveitis as a presenting feature of chronic sarcoidosis
- Author
-
A Tommasini, M Angi, E Pilotto, L. Montemurro, Gianfranco Rizzato, and Patrizia Fraioli
- Subjects
Pulmonary and Respiratory Medicine ,Adult ,Male ,medicine.medical_specialty ,Systemic disease ,Sarcoidosis ,Eye disease ,Diagnosis, Differential ,Uveitis ,Epidemiology ,medicine ,Humans ,Caucasian population ,Aged ,medicine.diagnostic_test ,Medical treatment ,business.industry ,Middle Aged ,medicine.disease ,Dermatology ,Surgery ,Chronic Disease ,Female ,Chest radiograph ,business ,Follow-Up Studies - Abstract
Uveitis is often a manifestation of sarcoidosis. Less well-recognized, however, is the development of uveitis several years before the diagnosis of systemic sarcoidosis. The possibility that presentation of uveitis is a marker for the chronicity of sarcoidosis has never been investigated. The aim of this work was to evaluate, in a Caucasian population, the epidemiology of uveitis as the primary manifestation of sarcoidosis with long-term follow-up, and the relationship of uveitis to the chronicity of sarcoidosis. The records of 1,156 Caucasian patients with histologically proven sarcoidosis, first seen in the period 1976-1992, were reviewed. In patients in whom uveitis was the primary feature of sarcoidosis, the following parameters were identified: systemic manifestations; time interval between the diagnosis of uveitis and sarcoidosis; therapy; the evolution of chest radiographic image over time; chronicity; the relationship between sarcoidosis and uveitis; and, finally, status in October 1994. In nine patients, uveitis was the reason for seeking medical treatment, resulting in the discovery of systemic sarcoidosis, which was then found to be chronic in 7 out of 9 cases. In an additional eight patients, uveitis preceded the diagnosis of systemic sarcoidosis by 1-11 yrs, and yet most subjects had systemic manifestations that went unrecognized during this time period, with chest radiograph at the time of diagnosis suggesting a long-standing chronic disease. Thus, uveitis appeared to be the primary manifestation of sarcoidosis in 17 of the 1,156 patients studied (1.5%). In conclusion, any uveitis of unknown origin may be due to sarcoidosis, although its systemic manifestations may not occur for up to 11 yrs. Uveitis patients need a very long-term follow-up, including periodic diagnostic tests for systemic sarcoidosis. Furthermore, when uveitis precedes the systemic symptoms and diagnosis of sarcoidosis by more than one year, it may be regarded as a marker of the chronicity of sarcoidosis.
- Published
- 1996
20. Efficacy of a three day course of azithromycin in moderately severe community-acquired pneumonia
- Author
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Guido Montanari, Gianfranco Rizzato, R. Pozzoli, Patrizia Fraioli, D. Fanti, L. Montemurro, and E. Magliano
- Subjects
Pulmonary and Respiratory Medicine ,Adult ,Male ,medicine.medical_specialty ,Mycoplasma pneumoniae ,Azithromycin ,medicine.disease_cause ,Drug Administration Schedule ,Sputum culture ,Community-acquired pneumonia ,Haemophilus parainfluenzae ,Clarithromycin ,Internal medicine ,Streptococcus pneumoniae ,medicine ,Pneumonia, Bacterial ,Humans ,medicine.diagnostic_test ,biology ,business.industry ,Middle Aged ,medicine.disease ,biology.organism_classification ,respiratory tract diseases ,Surgery ,Community-Acquired Infections ,Hospitalization ,Pneumonia ,Treatment Outcome ,Female ,business ,medicine.drug - Abstract
This study was designed to evaluate the efficacy of a 3 day course of azithromycin in low to moderately severe community-acquired pneumonia. Forty patients with low to moderately severe community-acquired pneumonia (29 males, 11 females, mean age 46 +/- 17 yrs; 20 pretreated with betalactams for 2-10 days with no results before admission to hospital; 18 with evidence of co-morbidity) were enrolled in an open, randomized study with azithromycin, 500 mg q.d. oral therapy for 3 days, versus clarithromycin, 250 mg b.i.d. oral therapy for 10 +/- 2 days. The aetiology of pneumonia was identified in 18 patients by serology (nine Mycoplasma pneumoniae, four Chlamydia pneumoniae, five Legionella pneumophila; one patient with chlamydial infection also had Klebsiella pneumoniae bacteraemia). A presumptive aetiological diagnosis was obtained with sputum culture in three other patients (one Haemophilus influenzae, two Haemophilus parainfluenzae), all strains were sole isolates with 10(8) Colony forming units (CFU), and with Gram stain in one patient with Streptococcus pneumoniae. All patients in the azithromycin group (one after a second 3 day course), and all but two (of those available for evaluation) of the clarithromycin group were cured. Defervescence occurred after 2.6 +/- 1.6 days, and chest roentgenogram cleared after 8.9 +/- 3.3 days, with no difference between the two groups. Tolerance was good, and there were no withdrawals from therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1995
21. Sarcoid extrapulmonary features. Shift of the bioptic approach from the mediastinoscopy to the pleuroscopy
- Author
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G, Rizzato, L, Montemurro, and P, Fraioli
- Subjects
Mediastinoscopy ,Sarcoidosis ,Sarcoidosis, Pulmonary ,Biopsy ,Humans ,Retrospective Studies - Published
- 1993
22. Is sarcoidosis a borreliosis?
- Author
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L, Montemurro and G, Rizzato
- Subjects
Adult ,Male ,Borrelia burgdorferi Group ,Sarcoidosis ,Humans ,Enzyme-Linked Immunosorbent Assay ,Female ,Middle Aged ,Antibodies, Bacterial - Abstract
Recently some Authors have suggested that sarcoidosis may be a borreliosis. Thus in the period April to June 1991 we studied serum samples of 12 sarcoid patients (pts) by ELISA in order to identify antibodies to Borrelia burgdorferi (Bb). None had positive results. We conclude that great caution is to be used in advancing the hypothesis of an etiologic role of Bb in sarcoidosis.
- Published
- 1991
23. Researching, monitoring and treating osteoporosis in a Sarcoid Clinic: seven years of experience and follow-up
- Author
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G, Rizzato, L, Montemurro, and P, Fraioli
- Subjects
Calcitonin ,Sarcoidosis ,Humans ,Osteoporosis ,Glucocorticoids ,Follow-Up Studies - Published
- 1991
24. Bone loss in untreated longstanding sarcoidosis
- Author
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L, Montemurro, P, Fraioli, and G, Rizzato
- Subjects
Adult ,Male ,Postmenopause ,Time Factors ,Sarcoidosis ,Bone Density ,Humans ,Osteoporosis ,Female ,Middle Aged ,Spine - Abstract
The introduction of new techniques for the study of Bone Mineral Content (BMC) has not yet been extensively applied to sarcoidosis. Using Quantitative Computed Tomography (QCT) in a long-term prednisone-treated sarcoid population we have shown in 1988 [1] that Bone Mineral Loss is more frequent than elsewhere reported with other techniques on patients with different diseases. It was not clear if this difference was due to the sarcoidosis itself or to the better sensitivity of QCT compared to former techniques [2]. Thus we have now studied QCT in a group of 36 untreated patients with active, histologically proven sarcoidosis, chronic in most cases, to clarify the action of sarcoidosis itself over the BMC. For each patient Vertebral Cancellous Mineral Content (VCMC) has been expressed in terms of Z score (i.e. the number of Standard Deviations (SD) above or below the normal value) in order to overcome the differences due to age and sex. In the whole group, mean value of Z score was -0.41 +/- 0.30 (P0.05 vs. 190 normals). Nevertheless VCMC was below the normal range in 13 out of 36 patients; in five of them, all with longstanding sarcoidosis for at least 2 years, VCMC was more than two SD below the normal; four out of 36 had a VCMC lower than 110 mg/cm3 K2HPO4 eq, that is considered the threshold level under which the risk of fracture begins (but three of them were postmenopausal females).(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1991
25. Long-term therapy with deflazacort in chronic sarcoidosis
- Author
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Gianfranco Rizzato, Patrizia Fraioli, and L. Montemurro
- Subjects
Pulmonary and Respiratory Medicine ,Adult ,Lung Diseases ,Male ,medicine.medical_specialty ,Time Factors ,Sarcoidosis ,medicine.drug_class ,Anti-Inflammatory Agents ,Peptidyl-Dipeptidase A ,Critical Care and Intensive Care Medicine ,Gastroenterology ,Pulmonary function testing ,Prednisone ,Pregnenediones ,Internal medicine ,medicine ,Humans ,Lung volumes ,Respiratory function ,Radionuclide Imaging ,Lung ,business.industry ,Respiratory disease ,Middle Aged ,medicine.disease ,Surgery ,Deflazacort ,Radiography ,Corticosteroid ,Calcium ,Female ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
To evaluate the long-term action of deflazacort (DF), a new calcium-sparing and bone-saving corticosteroid, in chronic sarcoidosis patients needing prolonged therapy.40 patients with chronic histologically proved sarcoidosis requiring long-term corticosteroid therapy were treated with DF and followed for a mean period of 958 +/- 515 days (range 382-2, 068). The indication for giving corticosteroid therapy was pulmonary impairment in most (36), but also other events including hypercalcemia (2), kidney stones (5, 2 with recurrent colic), uveitis (2), lupus pernio (3), suspected heart impairment (5), hypersplenism (1), and other causes. Follow-up examination included serial ACE, chest x-ray, 67Ga lung scan, pulmonary function data, serum and urinary calcium levels. Eleven patients (UT group) were not receiving glucocorticoids when first seen at our clinic; 29 patients (PT group) were on therapy with glucocorticoids (27 wity prednisone, 2 with DF) for 870 +/- 1,128 days (range 27-4,310)In the PT group, DF maintained the good results previously obtained with prednisone; in this group, chest x-ray film showed improvement in 16 patients, 67Ga lung scan was better in 13, while worsening chest x-ray film findings in 1 and 67Ga lung scan in 2 was seen coincident with DF tapering. Respiratory function data showed a mild nonsignificant improvement. SACE decreased significantly from 114.6 +/- 38.7 to 91.5 +/- 37.9 nM/ml/min (p less than .05). In the UT group the results were better, as expected in a population where the action of corticosteroids did not influence the first observation. FVC increased significantly from 76.3 +/- 13.0 to 89.9 +/- 19.5 percent predicted (p less than .01); the 67Ga lung scan and chest x-ray film findings improved in all but 1 patient, and ACE dropped significantly (p less than .01) from 131.8 +/- 46.3 to 83.7 +/- 25.0. In both groups the side effects were mild, and only 2 patients discontinued the treatment, 1 for gastric ulcer, and the other for amenorrhea plus a 14 kg weight gain.One patient died of cancer, 9 discontinued treatment (5 because therapy was no longer necessary, 2 for the above described side effects, 2 for non-drug-related reasons), 4 dropped out and were last seen when taking DF 22.5, 18, 12 and 6 mg daily respectively. Twenty-six are continuing the drug on a long-term basis at the current mean daily dose of 12.1 +/- 7.3 mg (range 3-30). In a number of these, an attempt to discontinue DF resulted in a sarcoid relapse, and DF was restarted.DF is a good and safe approach to the long-term corticosteroid therapy of sarcoidosis.
- Published
- 1991
26. Retroperitoneal involvement in sarcoidosis
- Author
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P, Fraioli, L, Montemurro, L, Castrignano, and G, Rizzato
- Subjects
Adult ,Male ,Cholestasis ,Sarcoidosis ,Humans ,Female ,Hydronephrosis ,Lymph Nodes ,Retroperitoneal Space ,Middle Aged ,Tomography, X-Ray Computed ,Aged ,Ureteral Obstruction - Abstract
The presence of retroperitoneal lymphnodes is well known in sarcoidosis. We observed in two patients unilateral hydronephrosis (asymptomatic in one; dysuria in the other), and in one patient urine retention due to compression of both ureters; this patient also had jaundice due to lymphnode compression of the biliary tract. In another four patients we noted retroperitoneal lymphnodes without compression. We conclude that retroperitoneal impairment may be a previously unreported complication of Sarcoidosis.
- Published
- 1990
27. Bone loss in prednisone treated sarcoidosis: a two-year follow-up
- Author
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L, Montemurro, P, Fraioli, A, Riboldi, S, Delpiano, D, Zanni, and G, Rizzato
- Subjects
Adult ,Male ,Time Factors ,Sarcoidosis ,Humans ,Osteoporosis ,Prednisone ,Female ,Menopause ,Middle Aged ,Models, Biological ,Aged - Abstract
We followed up 35 sarcoid patients treated with prednisone for two years in order to evaluate bone mineral loss over time. Vertebral cancellous mineral content was detected by quantitative computed tomography and calibration phantom before beginning prednisone therapy and monitored two more times at yearly intervals. The percent mineral loss (ML%) averaged -13.9 +/- 2.1 at the end of the first year and -15.3 +/- 2.6 at the end of second year. We conclude first, that the time course of mineral loss in prednisone treated sarcoidosis is similar to that of other diseases such as asthma and rheumatoid arthritis. In a separate group of 10 early postmenopausal females, we observed a greater ML% averaging -21.9 +/- 16.6 and -26.2 +/- 18.5, at the end of the first and second year respectively. Our second conclusion was thus that the synergic effect of postmenopausal status and prednisone therapy results in an ML% far more significant than expected from the two single conditions.
- Published
- 1990
28. Spontaneous regression of amiodarone pulmonary toxicity
- Author
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P, Fraioli, M, Barberis, and L, Montemurro
- Subjects
Male ,Radiography ,Pulmonary Fibrosis ,Remission, Spontaneous ,Amiodarone ,Humans ,Female ,Middle Aged ,Lung ,Aged - Abstract
Two patients with Amiodarone-induced interstitial lung disease are described. The pulmonary lung biopsy in one of them, as well as Chest X ray, BAL cellularity and pulmonary function data in both, are in agreement with the reports from the literature, while Ga lung scan was negative in one of the two, and positive in the other one. In both, a total resolution was seen six and four months respectively after discontinuation of Amiodarone therapy. Corticosteroid therapy could be advisable only when no spontaneous resolution occurs after tapering the drug.
- Published
- 1990
29. D78 Long-term effects of anti-hypertensive treatment on bi-ventricula mass and function
- Author
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L. Montemurro, M. Lombardo, A. Pezzano, S. Ferrari, G. Zaini, M. Broccolino, C. Alli, and Daniela Zanni
- Subjects
medicine.medical_specialty ,business.industry ,Internal medicine ,Anti hypertensive treatment ,Internal Medicine ,Cardiology ,Medicine ,business ,Term (time) - Published
- 1997
- Full Text
- View/download PDF
30. The reversibility of exogenous corticosteroid-induced osteoporosis
- Author
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L. Montemurro and G. Rizzato
- Subjects
Corticosteroid induced osteoporosis ,medicine.medical_specialty ,Endocrinology ,business.industry ,Internal medicine ,Medicine ,Surgery ,business ,Biochemistry - Published
- 1992
- Full Text
- View/download PDF
31. Salmon calcitonin nasal spray in corticosteroid — Induced osteoporosis
- Author
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L. Montemurro, M.G. Brambilla, P. Fraioli, and G. Rizzato
- Subjects
medicine.medical_specialty ,Corticosteroid induced osteoporosis ,Endocrinology ,business.industry ,Internal medicine ,medicine ,Surgery ,Salmon calcitonin Nasal Spray ,business ,Biochemistry - Published
- 1992
- Full Text
- View/download PDF
32. Efficacy and tolerability of long-term (6-month) Protirelin Tartrate treatment in patients surviving after cerebral stroke
- Author
-
G. Montanari, G. Rizzato, P. Fraioli, and L. Montemurro
- Subjects
Pharmacology ,medicine.medical_specialty ,business.industry ,Cerebral stroke ,Tartrate ,Surgery ,chemistry.chemical_compound ,Tolerability ,chemistry ,Anesthesia ,Medicine ,Protirelin ,In patient ,business - Published
- 1990
- Full Text
- View/download PDF
33. MYCN is a novel oncogenic target in pediatric T-cell acute lymphoblastic leukemia
- Author
-
ASTOLFI, ANNALISA, F. Vendemini, URBINI, MILENA, F. Melchionda, MASETTI, RICCARDO, M. Franzoni, V. Libri, S. Serravalle, TOGNI, MARCO, L. Montemurro, R. Rondelli, G. Paone, BRESSANIN, DANIELA, F. Chiarini, MARTELLI, ALBERTO MARIA, TONELLI, ROBERTO, PESSION, ANDREA, A. Astolfi, F. Vendemini, M. Urbini, F. Melchionda, R. Masetti, M. Franzoni, V. Libri, S. Serravalle, M. Togni, L. Montemurro, R. Rondelli, G. Paone, D. Bressanin, F. Chiarini, A.M. Martelli, R. Tonelli, and A. Pession.
- Subjects
Male ,T cell ,Biology ,MYCN ,Pediatric T-ALL ,Peptide nucleic acid ,TAL1 ,Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ,Transfection ,N-Myc Proto-Oncogene Protein ,TGF-β inhibitors ,Precursor cell ,Cell Line, Tumor ,Proto-Oncogene Proteins ,medicine ,Basic Helix-Loop-Helix Transcription Factors ,Gene silencing ,Humans ,Viability assay ,Gene Silencing ,Molecular Targeted Therapy ,Child ,neoplasms ,T-Cell Acute Lymphocytic Leukemia Protein 1 ,Oncogene Proteins ,Gene knockdown ,Oncogene ,Gene Expression Regulation, Leukemic ,Gene Expression Profiling ,Nuclear Proteins ,pediatric T-ALL ,Molecular biology ,medicine.anatomical_structure ,Treatment Outcome ,MYCN, Pediatric T-ALL, Peptide nucleic acid, TAL1 ,Oncology ,Case-Control Studies ,Child, Preschool ,Gene Knockdown Techniques ,Cancer research ,peptide nucleic acid ,Female ,N-Myc ,Research Paper ,Transcription Factors - Abstract
MYCN is an oncogene frequently overexpressed in pediatric solid tumors whereas few evidences suggest his involvement in the pathogenesis of haematologic malignancies. Here we show that MYCN is overexpressed in a relevant proportion (40 to 50%) of adult and pediatric T-cell acute lymphoblastic leukemias (T-ALL). Focusing on pediatric T-ALL, MYCN-expressing samples were found almost exclusively in the TAL1-positive subgroup. Moreover, TAL1 knockdown in T-ALL cell lines resulted in a reduction of MYCN expression, and TAL1 directly binds to MYCN promoter region, suggesting that TAL1 pathway activation could sustain the up-regulation of MYCN. The role of MYCN in T-ALL was investigated by peptide nucleic acid (PNA-MYCN)-mediated transcriptional silencing of MYCN and by siRNAs. MYCN knockdown in T-ALL cell lines resulted in a reduction of cell viability, up to 50%, while no effect was elicited with a mismatch PNA. The inhibitory effect of PNA-MYCN on cell viability was due to a significant increase in apoptosis. PNA-MYCN treatment in pediatric T-ALL samples reduced cell viability of leukemic cells from patients with high MYCN expression, while no effect was obtained in MYCN-negative blast cells. These results showed that MYCN is frequently overexpressed in pediatric T-ALL and suggested his role as a candidate for molecularly-directed therapies.
34. The Milan Conference on Sarcoidosis and Other Granulomatous Disorders. Clinical highlights
- Author
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G, Rizzato and L, Montemurro
- Subjects
Granuloma ,Sarcoidosis ,Humans - Published
- 1988
35. A new approach to the study of pneumoconiosis: the nuclear reactor
- Author
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G, Rizzato, S, Sabbioni, R, Pietra, P, Fraioli, L, Montemurro, M, Barberis, and M, Torre
- Subjects
Lung Diseases ,Male ,Time Factors ,Sarcoidosis ,Humans ,Cobalt ,Neutron Activation Analysis ,Pneumoconiosis ,Tantalum ,Middle Aged ,Tungsten - Published
- 1989
36. Prednisone-induced bone loss in sarcoidosis: a risk especially frequent in postmenopausal women
- Author
-
G, Rizzato, G, Tosi, C, Mella, L, Montemurro, D, Zanni, and S, Sisti
- Subjects
Adult ,Male ,Minerals ,Lumbar Vertebrae ,Sarcoidosis ,Middle Aged ,Radiography ,Risk Factors ,Humans ,Osteoporosis ,Prednisone ,Female ,Menopause ,Aged - Abstract
The incidence of glucocorticoid-induced osteoporosis is reported in about 40 to 50% of treated patients, but it has never been extensively studied in sarcoidosis. We have studied Vertebral Cancellous Mineral Content (VCMC) of the lumbar spine by Quantitative Computed Tomography (QCT) in 190 normal subjects, 7 patients with sarcoid on no treatment and 64 patients with sarcoid on treatment with prednisone. As compared to the 190 normal subjects and the 7 untreated patients, VCMC was reduced in 46 of 64 patients with sarcoid on treatment with prednisone. Loss of VCMC in the patients varied directly with dose and duration of prednisone treatment. It is concluded that - in sarcoid patients and especially in postmenopausal females - long-term prednisone therapy results in bone mineral loss more frequently than elsewhere reported for other groups of patients. It is not clear if this difference is due to the sarcoidosis itself or to the better sensitivity of Computed Tomography compared to former techniques.
- Published
- 1988
37. Bone protection with salmon calcitonin (sCT) in the long-term steroid therapy of chronic sarcoidosis
- Author
-
G, Rizzato, G, Tosi, G, Schiraldi, L, Montemurro, D, Zanni, and S, Sisti
- Subjects
Adult ,Calcitonin ,Male ,Minerals ,Sarcoidosis ,Chronic Disease ,Humans ,Osteoporosis ,Prednisone ,Female ,Menopause ,Middle Aged ,Spine - Abstract
Prednisone-induced osteoporosis is very frequent in the long-term treatment of sarcoidosis (sarcoidosis 4:45-48, 1987). The aim of this work is to evaluate if salmon Calcitonin (sCT) is able to prevent osteopenia in the long-term. We have studied 53 patients with chronic histologically-proven sarcoidosis, all needing steroids, in a follow-up of 15 months; 20 of them were protected with sCT (100 I.U. i.m. daily for one month, then every two days for all the time of the study), 33 were unprotected. The two groups were matched for age, sex and total dose of prednisone. In order to overcome the differences of Vertebral Cancellous Mineral Content (VCMC) due to age and sex, we express VCMC in terms of Z score, i.e. the number of standard deviations above or below our normal means: initial Z score was -1.77 +/- 0.16 in the sCT group and -0.99 +/- 0.17 in the other group (P less than .05). For each subject we calculated the Mineral Loss (ML) in % of the initial value. At the end of the study ML% averaged -2.15(+/- 2.27) in the sCT protected group, and -14.11(+/- 2.08) in the unprotected group (P less than .001). We have also analysed the results limited to pts with initial Z score under -1 (19 sCT protected pts vs 18 unprotected). In these subgroups the ML% after 15 months averaged -13.62(+/- 2.9) in the unprotected group and -2.80(+/- 2.29) in the protected one (P less than .01). Finally we have studied another subgroup, i.e. 21 postmenopausal females: 9 were sCT protected, 12 were unprotected.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1988
38. Down-regulation of HOXA4, HOXA7, HOXA10, HOXA11 and MEIS1 during monocyte-macrophage differentiation in THP-1 cells
- Author
-
Annalisa Bianchera, Roberto Tonelli, Luca Montemurro, Raffaella Fazzina, Gian C. Gazzola, Vincenzo Martino, Roberto Sala, Flora Marino, Ovidio Bussolati, L. Reia, Andrea Pession, V MARTINO, A BIANCHERA, L REIA, O BUSSOLATI, R FAZZINA, F MARINO, L MONTEMURRO, R TONELLI, A PESSION, GC GAZZOLA, and R SALA
- Subjects
Cancer Research ,HOXA4 ,Chromosomal translocation ,HOXA ,Biology ,medicine.disease_cause ,MLL-AF9 ,MEIS1 ,Biochemistry ,chemistry.chemical_compound ,hemic and lymphatic diseases ,Genetics ,medicine ,THP1 cell line ,neoplasms ,Molecular Biology ,Oncogene ,Myeloid leukemia ,Cell biology ,DIFFERENTIATION ,Oncology ,chemistry ,Phorbol ,Molecular Medicine ,Carcinogenesis ,A431 cells ,ACUTE MYELOID LEUKAEMIA - Abstract
The translocation t(9;11)(p22;q23) generates the MLL-AF9 oncogene and is commonly associated with monocytic acute myeloid leukemia (AML-M5; FAB-classification). For the oncogenicity of MLL-AF9, the (over)expression of several other genes, including selected HOXA cluster genes as well as MEIS1 (a HOX cofactor), is required. We previously showed that the down-regulation of MLL-AF9 expression is not obligatory for monocyte-macrophage maturation in AML-M5 cells carrying t(9;11)(p22;q23). In this study, we analyzed the expression patterns of HOXA4, 5, 6, 7, 9, 10 and 11 (defined as ‘HOXA-code’ genes) and MEIS1 by semiquantitative RT-PCR during the monocytemacrophage differentiation induced by phorbol 12-myristate 13-acetate (PMA) in THP-1 cells carrying t(9;11)(p22;q23) and expressing MLL-AF9. The analyses were performed in THP-1 cells expressing MLL-AF9 even after PMA treatment. The results showed that all the analyzed genes were expressed in untreated THP-1 cells. After the induction of differentiation, we observed a down-regulation of HOXA4, 7, 10, 11 and MEIS1, an up-regulation of HOXA6, and no significant variation in the expression of HOXA5 and 9. These data indicate that the expression of most HOXA-code genes, as well as MEIS1, could be implicated in the differentiation blockage observed in MLL-AF9-related leukemias.
- Published
- 2011
39. Preclinical Pharmacokinetics in Tumors and Normal Tissues of the Antigene PNA Oligonucleotide MYCN-Inhibitor BGA002.
- Author
-
Scardovi AL, Bartolucci D, Montemurro L, Bortolotti S, Angelucci S, Amadesi C, Nieddu G, Oosterholt S, Cerisoli L, Della Pasqua O, Hrelia P, and Tonelli R
- Subjects
- Animals, Mice, Female, Humans, Male, Tissue Distribution, Cell Line, Tumor, Rhabdomyosarcoma genetics, Rhabdomyosarcoma drug therapy, Rhabdomyosarcoma pathology, Nuclear Proteins genetics, Nuclear Proteins antagonists & inhibitors, Organic Chemicals, N-Myc Proto-Oncogene Protein genetics, N-Myc Proto-Oncogene Protein antagonists & inhibitors, Peptide Nucleic Acids pharmacokinetics, Peptide Nucleic Acids chemistry, Peptide Nucleic Acids administration & dosage, Peptide Nucleic Acids genetics, Neuroblastoma drug therapy, Neuroblastoma pathology, Neuroblastoma genetics
- Abstract
Although MYCN has been considered an undruggable target, MYCN alterations confer poor prognosis in many pediatric and adult cancers. The novel MYCN -specific inhibitor BGA002 is an antigene peptide nucleic acid oligonucleotide covalently bound to a nuclear localization signal peptide. In the present study, we characterized the pharmacokinetics (PK) of BGA002 after single and repeated administration to mice using a novel specific enzyme-linked immunosorbent assay. BGA002 concentrations in plasma showed linear PK, with dose proportional increase across the tested dose levels and similar exposure between male and female and between intravenous and subcutaneous route of administration. Repeated dosing resulted in no accumulation in plasma. Biodistribution up to 7 days after single subcutaneous administration of [
14 C]-radiolabeled BGA002 showed broad tissues and organ distribution (suggesting a potential capability to reach primary tumor and metastasis in several body sites), with high concentrations in kidney, liver, spleen, lymph nodes, adrenals, and bone marrow. Remarkably, we demonstrated that BGA002 concentrates in tumors after repeated systemic administrations in three mouse models with MYCN amplification (neuroblastoma, rhabdomyosarcoma, and small-cell lung cancer), leading to a significant reduction in tumor weight. Taking into account the available safety profile of BGA002, these data support further evaluation of BGA002 in patients with MYCN -positive tumors.- Published
- 2024
- Full Text
- View/download PDF
40. Antigene MYCN Silencing by BGA002 Inhibits SCLC Progression Blocking mTOR Pathway and Overcomes Multidrug Resistance.
- Author
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Bortolotti S, Angelucci S, Montemurro L, Bartolucci D, Raieli S, Lampis S, Amadesi C, Scardovi A, Nieddu G, Cerisoli L, Paganelli F, Chiarini F, Teti G, Falconi M, Pession A, Hrelia P, and Tonelli R
- Abstract
Small-cell lung cancer (SCLC) is the most aggressive lung cancer type, and is associated with smoking, low survival rate due to high vascularization, metastasis and drug resistance. Alterations in MYC family members are biomarkers of poor prognosis for a large number of SCLC. In particular, MYCN alterations define SCLC cases with immunotherapy failure. MYCN has a highly restricted pattern of expression in normal cells and is an ideal target for cancer therapy but is undruggable by traditional approaches. We propose an innovative approach to MYCN inhibition by an MYCN -specific antigene-PNA oligonucleotide (BGA002)-as a new precision medicine for MYCN -related SCLC. We found that BGA002 profoundly and specifically inhibited MYCN expression in SCLC cells, leading to cell-growth inhibition and apoptosis, while also overcoming multidrug resistance. These effects are driven by mTOR pathway block in concomitance with autophagy reactivation, thus avoiding the side effects of targeting mTOR in healthy cells. Moreover, we identified an MYCN -related SCLC gene signature comprehending CNTFR , DLX5 and TNFAIP3 , that was reverted by BGA002. Finally, systemic treatment with BGA002 significantly increased survival in MYCN -amplified SCLC mouse models, including in a multidrug-resistant model in which tumor vascularization was also eliminated. These findings warrant the clinical testing of BGA002 in MYCN -related SCLC., Competing Interests: R. Tonelli and A. Pession are BIOGENERA shareholders. C. Amadesi, D. Bartolucci, S. Bortolotti, S. Angelucci, A. Scardovi, G. Nieddu, and L. Cerisoli are employed at BIOGENERA. The authors declare no potential conflicts of interest.
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- 2023
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41. MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment.
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Bartolucci D, Montemurro L, Raieli S, Lampis S, Pession A, Hrelia P, and Tonelli R
- Abstract
Among childhood cancers, neuroblastoma is the most diffuse solid tumor and the deadliest in children. While to date, the pathology has become progressively manageable with a significant increase in 5-year survival for its less aggressive form, high-risk neuroblastoma (HR-NB) remains a major issue with poor outcome and little survivability of patients. The staging system has also been improved to better fit patient needs and to administer therapies in a more focused manner in consideration of pathology features. New and improved therapies have been developed; nevertheless, low efficacy and high toxicity remain a staple feature of current high-risk neuroblastoma treatment. For this reason, more specific procedures are required, and new therapeutic targets are also needed for a precise medicine approach. In this scenario, MYCN is certainly one of the most interesting targets. Indeed, MYCN is one of the most relevant hallmarks of HR-NB, and many studies has been carried out in recent years to discover potent and specific inhibitors to block its activities and any related oncogenic function. N-Myc protein has been considered an undruggable target for a long time. Thus, many new indirect and direct approaches have been discovered and preclinically evaluated for the interaction with MYCN and its pathways; a few of the most promising approaches are nearing clinical application for the investigation in HR-NB.
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- 2022
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42. The MYCN inhibitor BGA002 restores the retinoic acid response leading to differentiation or apoptosis by the mTOR block in MYCN-amplified neuroblastoma.
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Lampis S, Raieli S, Montemurro L, Bartolucci D, Amadesi C, Bortolotti S, Angelucci S, Scardovi AL, Nieddu G, Cerisoli L, Paganelli F, Valente S, Fischer M, Martelli AM, Pasquinelli G, Pession A, Hrelia P, and Tonelli R
- Subjects
- Animals, Child, Humans, Mice, Apoptosis, N-Myc Proto-Oncogene Protein genetics, N-Myc Proto-Oncogene Protein metabolism, TOR Serine-Threonine Kinases, Neuroblastoma drug therapy, Neuroblastoma genetics, Neuroblastoma metabolism, Tretinoin pharmacology, Tretinoin therapeutic use
- Abstract
Background: Neuroblastoma is a deadly childhood cancer, and MYCN-amplified neuroblastoma (MNA-NB) patients have the worst prognoses and are therapy-resistant. While retinoic acid (RA) is beneficial for some neuroblastoma patients, the cause of RA resistance is unknown. Thus, there remains a need for new therapies to treat neuroblastoma. Here we explored the possibility of combining a MYCN-specific antigene oligonucleotide BGA002 and RA as therapeutic approach to restore sensitivity to RA in NB., Methods: By molecular and cellular biology techniques, we assessed the combined effect of the two compounds in NB cell lines and in a xenograft mouse model MNA-NB., Results: We found that MYCN-specific inhibition by BGA002 in combination with RA (BGA002-RA) act synergistically and overcame resistance in NB cell lines. BGA002-RA also reactivated neuron differentiation (or led to apoptosis) and inhibited invasiveness capacity in MNA-NB. Moreover, we found that neuroblastoma had the highest level of mRNA expression of mTOR pathway genes, and that BGA002 led to mTOR pathway inhibition followed by autophagy reactivation in MNA-NB cells, which was strengthened by BGA002-RA. BGA002-RA in vivo treatment also eliminated tumor vascularization in a MNA-NB mouse model and significantly increased survival., Conclusion: Taken together, MYCN modulation mediates the therapeutic efficacy of RA and the development of RA resistance in MNA-NB. Furthermore, by targeting MYCN, a cancer-specific mTOR pathway inhibition occurs only in MNA-NB, thus avoiding the side effects of targeting mTOR in normal cells. These findings warrant clinical testing of BGA002-RA as a strategy for overcoming RA resistance in MNA-NB., (© 2022. The Author(s).)
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- 2022
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43. Efficacy and Safety of Remdesivir over Two Waves of the SARS-CoV-2 Pandemic.
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Poliseno M, Gallo C, Cibelli DC, Minafra GA, Bottalico IF, Bruno SR, D'Errico ML, Montemurro L, Rizzo M, Barbera L, Custodero GE, La Marca A, Lo Muzio D, Miucci A, Santantonio TA, and Lo Caputo S
- Abstract
The aim of this study is to describe the features, the outcomes, and the clinical issues related to Remdesivir administration of a cohort of 220 patients (pts) with COVID-19 hospitalized throughout the last two pandemic waves in Italy. One hundred and nine pts were enrolled from 1 September 2020, to 28 February 2021 (Group A) and 111 from 1 March to 30 September 2021 (Group B). Notably, no differences were reported between the two groups neither in the timing of hospitalization. nor in the timing of Remdesivir administration from symptoms onset. Remarkably, a higher proportion of pts with severe COVID-19 was observed in Group B (25% vs. 10%, p < 0.001). At univariate and multivariate analysis, rather than the timing of Remdesivir administration, age, presence of coexisting conditions, D-dimers, and O2 flow at admission correlated positively to progression to non-invasive ventilation, especially for patients in Group B. However, the rate of admission in the Intensive Care Unit and/or death was comparable in the two groups (7% vs. 4%). Negligible variations in serum GOT, GPT, GGT, and eGFR levels were detected. A mean reduction in heart rate was noticed within the first three days of antiviral treatment ( p < 0.001). Low rate of ICU admission, high rate of clinical recovery, and good drug safety were observed in COVID-19 patients treated with Remdesivir during two diverse pandemic waves.
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- 2021
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44. Safety and heart rate changes in Covid-19 patients treated with Remdesivir.
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Brunetti ND, Poliseno M, Bottalico IF, Centola A, Montemurro L, Sica S, Santantonio T, and Lo Caputo S
- Subjects
- Adenosine Monophosphate analogs & derivatives, Alanine analogs & derivatives, Antiviral Agents therapeutic use, Heart Rate, Humans, SARS-CoV-2, COVID-19 Drug Treatment
- Abstract
Objectives: Limited data are available regarding the occurrence and the extent of cardiac rhythm disturbances in patients with COVID-19 treated with Remdesivir., Methods: We present a case series of 52 patients who underwent daily electrocardiogram (ECG) examination after Remdesivir administration., Results: Compared to baseline, a significant heart rate reduction was observed after initiation of Remdesivir; however, no case of severe bradycardia or arrhythmias leading to significant clinical complications or Remdesivir discontinuation occurred. Heart rate reduction was proportional to baseline heart rate values (r=0.75, p<0.001). By multivariate analysis, a less severe clinical presentation of Covid-19 (beta=0.47, p<0.01) was related to lower heart rate levels observed after Remdesivir administration., Conclusions: Despite a significant reduction in heart rate observed after Remdesivir administration, no severe cardiovascular toxicity was observed in Covid-19 patients, even in the case of cardiovascular comorbidities., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2021
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45. Guillain-Barré syndrome as only manifestation of COVID-19 infection.
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d'Orsi G, Sica S, Maiorano A, Melchionda D, Lalla A, Montemurro L, Sabetta A, Goffredo R, Lecce B, Fiore JR, Santantonio T, and Avolio C
- Subjects
- COVID-19 therapy, Guillain-Barre Syndrome therapy, Humans, Male, Middle Aged, Plasma Exchange methods, COVID-19 complications, COVID-19 diagnostic imaging, Guillain-Barre Syndrome diagnostic imaging, Guillain-Barre Syndrome etiology
- Abstract
Post-infectious/immune mediated effects of COVID-19 infection include descriptions of Guillain-Barré syndrome (GBS) in patients usually with respiratory failure and after 1-2 weeks from the onset of viral illness. Asymptomatic cases for COVID-19 infection were rarely described. Herein, we studied a 62-year-old patient with progressive weakness of lower extremities, rapidly evolving to a severe, flaccid tetraplegia and dysphagia. Neurological symptoms weren't preceded by fever or pulmonary symptoms. Because of laboratory test abnormalities (thrombocytopenia, lymphocytopenia, high inflammation indexes), the patient underwent to nasopharyngeal swab, resulted positive for SARS-CoV-2 on RT-PCR assay; cerebrospinal fluid (CSF) was negative for SARS-CoV-2. The clinical (severe symmetric distal upper and lower limbs weakness, grade 0/5; decreased proprioceptive sensitivity and hypoesthesia involving the four limbs; loss of deep tendon reflexes), electrophysiological (prevailing axonal polyradiculoneuritis) and CSF features (albumino-cytological dissociation) disclosed the GBS diagnosis (level 1 of diagnostic certainty according to the Brighton criteria). The patient received plasma exchange and immunoglobulin, and, at 4 weeks after treatment and physical therapy, the patient had moderate improvement (weakness at lower and upper extremities was grade 2/5 and 3/5, respectively). Neurologists and clinicians should be aware of the possible link between neurological symptoms and COVID-19 infection, not only after viral prodrome and pulmonary symptoms, but also without COVID-19 symptoms., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2021
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46. Two nasal swabs may not be enough to exclude SARS-CoV-2 infection in symptomatic patients.
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Fiore JR, D'Errico M, Bottalico I, Rizzo M, Montemurro L, Lo Caputo S, Faleo G, Di Stefano M, and Santantonio T
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- Aged, Humans, Male, Nasopharynx virology, Symptom Assessment, COVID-19 diagnosis, COVID-19 Nucleic Acid Testing methods, SARS-CoV-2 isolation & purification
- Abstract
Abstracts: The spread of COVID-19 (COronaVIrus Disease 2019), due to SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2) has taken on dramatic pandemic proportions, affecting over 100 countries in a matter of weeks. Italy has had 237,828 confirmed cases according to the Istituto Superiore di Sanità as of May 13, and 34,448 deaths (1).
- Published
- 2021
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47. MYCN Drives a Tumor Immunosuppressive Environment Which Impacts Survival in Neuroblastoma.
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Raieli S, Di Renzo D, Lampis S, Amadesi C, Montemurro L, Pession A, Hrelia P, Fischer M, and Tonelli R
- Abstract
A wide range of malignancies presents MYCN amplification (MNA) or dysregulation. MYCN is associated with poor prognosis and its over-expression leads to several dysregulations including metabolic reprogramming, mitochondria alteration, and cancer stem cell phenotype. Some hints suggest that MYCN overexpression leads to cancer immune-escape. However, this relationship presents various open questions. Our work investigated in details the relationship of MYCN with the immune system, finding a correlated immune-suppressive phenotype in neuroblastoma (NB) and different cancers where MYCN is up-regulated. We found a downregulated Th1-lymphocytes/M1-Macrophages axis and upregulated Th2-lymphocytes/M2-macrophages in MNA NB patients. Moreover, we unveiled a complex immune network orchestrated by N-Myc and we identified 16 genes modules associated to MNA NB. We also identified a MYCN -associated immune signature that has a prognostic value in NB and recapitulates clinical features. Our signature also discriminates patients with poor survival in non-MNA NB patients where MYCN expression is not discriminative. Finally, we showed that targeted inhibition of MYCN by BGA002 (anti- MYCN antigene PNA) is able to restore NK sensibility in MYCN -expressing NB cells. Overall, our study unveils a MYCN- driven immune network in NB and shows a therapeutic option to restore sensibility to immune cells., Competing Interests: RT and AP are co-founders and shareholders of Biogenera. Authors SR, SL and CA are employed by Biogenera. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Raieli, Di Renzo, Lampis, Amadesi, Montemurro, Pession, Hrelia, Fischer and Tonelli.)
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- 2021
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48. A Novel MYCN-Specific Antigene Oligonucleotide Deregulates Mitochondria and Inhibits Tumor Growth in MYCN-Amplified Neuroblastoma.
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Montemurro L, Raieli S, Angelucci S, Bartolucci D, Amadesi C, Lampis S, Scardovi AL, Venturelli L, Nieddu G, Cerisoli L, Fischer M, Teti G, Falconi M, Pession A, Hrelia P, and Tonelli R
- Subjects
- Adolescent, Adult, Animals, Apoptosis drug effects, Cell Differentiation drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Child, Child, Preschool, Female, HSP90 Heat-Shock Proteins metabolism, Humans, Infant, Infant, Newborn, Kaplan-Meier Estimate, Male, Mice, Mitochondria metabolism, Mitochondria pathology, Mitophagy drug effects, N-Myc Proto-Oncogene Protein antagonists & inhibitors, N-Myc Proto-Oncogene Protein genetics, Neuroblastoma drug therapy, Neuroblastoma genetics, Neuroblastoma mortality, Peptide Nucleic Acids genetics, Peptide Nucleic Acids therapeutic use, Prognosis, RNA, Messenger genetics, RNA, Messenger metabolism, Reactive Oxygen Species metabolism, Xenograft Model Antitumor Assays, Young Adult, Gene Expression Regulation, Neoplastic drug effects, Mitochondria drug effects, N-Myc Proto-Oncogene Protein metabolism, Neuroblastoma pathology, Peptide Nucleic Acids pharmacology
- Abstract
Approximately half of high-risk neuroblastoma is characterized by MYCN amplification. N-Myc promotes tumor progression by inducing cell growth and inhibiting differentiation. MYCN has also been shown to play an active role in mitochondrial metabolism, but this relationship is not well understood. Although N-Myc is a known driver of the disease, it remains a target for which no therapeutic drug exists. Here, we evaluated a novel MYCN-specific antigene PNA oligonucleotide (BGA002) in MYCN-amplified (MNA) or MYCN-expressing neuroblastoma and investigated the mechanism of its antitumor activity. MYCN mRNA and cell viability were reduced in a broad set of neuroblastoma cell lines following BGA002 treatment. Furthermore, BGA002 decreased N-Myc protein levels and apoptosis in MNA neuroblastoma. Analysis of gene expression data from patients with neuroblastoma revealed that MYCN was associated with increased reactive oxygen species (ROS), downregulated mitophagy, and poor prognosis. Inhibition of MYCN caused profound mitochondrial damage in MNA neuroblastoma cells through downregulation of the mitochondrial molecular chaperone TRAP1, which subsequently increased ROS. Correspondingly, inhibition of MYCN reactivated mitophagy. Systemic administration of BGA002 downregulated N-Myc and TRAP1, with a concomitant decrease in MNA neuroblastoma xenograft tumor weight. In conclusion, this study highlights the role of N-Myc in blocking mitophagy in neuroblastoma and in conferring protection to ROS in mitochondria through upregulation of TRAP1. BGA002 is a potently improved MYCN-specific antigene oligonucleotide that reverts N-Myc-dysregulated mitochondrial pathways, leading to loss of the protective effect of N-Myc against mitochondrial ROS. SIGNIFICANCE: A second generation antigene peptide oligonucleotide targeting MYCN induces mitochondrial damage and inhibits growth of MYCN-amplified neuroblastoma cells., (©2019 American Association for Cancer Research.)
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- 2019
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49. MYCN is a novel oncogenic target in pediatric T-cell acute lymphoblastic leukemia.
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Astolfi A, Vendemini F, Urbini M, Melchionda F, Masetti R, Franzoni M, Libri V, Serravalle S, Togni M, Paone G, Montemurro L, Bressanin D, Chiarini F, Martelli AM, Tonelli R, and Pession A
- Subjects
- Basic Helix-Loop-Helix Transcription Factors genetics, Basic Helix-Loop-Helix Transcription Factors metabolism, Case-Control Studies, Cell Line, Tumor, Child, Child, Preschool, Female, Gene Expression Profiling, Gene Expression Regulation, Leukemic, Gene Knockdown Techniques, Gene Silencing, Humans, Male, Molecular Targeted Therapy, N-Myc Proto-Oncogene Protein, Nuclear Proteins biosynthesis, Nuclear Proteins metabolism, Oncogene Proteins biosynthesis, Oncogene Proteins metabolism, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma metabolism, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, T-Cell Acute Lymphocytic Leukemia Protein 1, Transfection, Treatment Outcome, Nuclear Proteins genetics, Oncogene Proteins genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma genetics, Transcription Factors genetics
- Abstract
MYCN is an oncogene frequently overexpressed in pediatric solid tumors whereas few evidences suggest his involvement in the pathogenesis of haematologic malignancies. Here we show that MYCN is overexpressed in a relevant proportion (40 to 50%) of adult and pediatric T-cell acute lymphoblastic leukemias (T-ALL). Focusing on pediatric T-ALL, MYCN-expressing samples were found almost exclusively in the TAL1-positive subgroup. Moreover, TAL1 knockdown in T-ALL cell lines resulted in a reduction of MYCN expression, and TAL1 directly binds to MYCN promoter region, suggesting that TAL1 pathway activation could sustain the up-regulation of MYCN. The role of MYCN in T-ALL was investigated by peptide nucleic acid (PNA-MYCN)-mediated transcriptional silencing of MYCN and by siRNAs. MYCN knockdown in T-ALL cell lines resulted in a reduction of cell viability, up to 50%, while no effect was elicited with a mismatch PNA. The inhibitory effect of PNA-MYCN on cell viability was due to a significant increase in apoptosis. PNA-MYCN treatment in pediatric T-ALL samples reduced cell viability of leukemic cells from patients with high MYCN expression, while no effect was obtained in MYCN-negative blast cells. These results showed that MYCN is frequently overexpressed in pediatric T-ALL and suggested his role as a candidate for molecularly-directed therapies.
- Published
- 2014
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50. Down-regulation of HOXA4, HOXA7, HOXA10, HOXA11 and MEIS1 during monocyte-macrophage differentiation in THP-1 cells.
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Martino V, Bianchera A, Reia L, Bussolati O, Fazzina R, Marino F, Montemurro L, Tonelli R, Pession A, Gazzola GC, and Sala R
- Abstract
The translocation t(9;11)(p22;q23) generates the MLL-AF9 oncogene and is commonly associated with monocytic acute myeloid leukemia (AML-M5; FAB-classification). For the oncogenicity of MLL-AF9, the (over)expression of several other genes, including selected HOXA cluster genes as well as MEIS1 (a HOX cofactor), is required. We previously showed that the down-regulation of MLL-AF9 expression is not obligatory for monocyte-macrophage maturation in AML-M5 cells carrying t(9;11)(p22;q23). In this study, we analyzed the expression patterns of HOXA4, 5, 6, 7, 9, 10 and 11 (defined as 'HOXA-code' genes) and MEIS1 by semiquantitative RT-PCR during the monocyte-macrophage differentiation induced by phorbol 12-myristate 13-acetate (PMA) in THP-1 cells carrying t(9;11)(p22;q23) and expressing MLL-AF9. The analyses were performed in THP-1 cells expressing MLL-AF9 even after PMA treatment. The results showed that all the analyzed genes were expressed in untreated THP-1 cells. After the induction of differentiation, we observed a down-regulation of HOXA4, 7, 10, 11 and MEIS1, an up-regulation of HOXA6, and no significant variation in the expression of HOXA5 and 9. These data indicate that the expression of most HOXA-code genes, as well as MEIS1, could be implicated in the differentiation blockage observed in MLL-AF9-related leukemias.
- Published
- 2009
- Full Text
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