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Biomedical subjects

A Moretti

Publications and source records attributed to A Moretti.

At least 37 records · Page 2Linked to original sources
PubMed2003

Staging of digestive endocrine tumours using helical computed tomography and somatostatin receptor scintigraphy.

BACKGROUND: In patients with digestive endocrine tumours, complete pre-operative staging is essential in planning proper management and evaluating treatment efficacy. To date, somatostatin receptor scintigraphy (SRS) is considered the 'gold standard' imaging procedure, and very few data are available concerning the use of helical computed tomography (hCT). This study aimed to determine the diagnostic accuracy and the ability to modify the surgical management of hCT, alone or combined with SRS. PATIENTS AND METHODS: Sixty patients were staged before surgery by hCT, SRS and tumour markers, and included in group 1 if suitable for radical surgery, otherwise in group 2. All patients underwent laparotomy followed by subsequent re-staging. RESULTS: SRS sensitivity was 77%, 48% and 67% for primary, lymph-node and liver lesions, respectively. hCT sensitivity was 94%, 69% and 94% for primary, lymph-node and liver lesions, respectively (P = 0.02 versus SRS, for liver lesions). During pre-operative evaluation, hCT correctly staged 92% and SRS 75% of patients (P = 0.02). hCT provided additional information in 17% of patients. CONCLUSIONS: Since hCT has been shown to be extremely accurate, providing essential information for the planning of surgical treatment compared with that of SRS, both techniques should be used in the pre-operative work-up of digestive endocrine tumours.

Adolescent↗
PubMed2003

[Surgical treatment of malignant lip tumors. Personal experience].

The malignant tumours of the lip account for nearly 1-2% of the cervicofacial neoplasms. These lesions are frequently spinous cell carcinomas and basal cell carcinomas (25% of all oral cancers). The spinous cell carcinoma is mainly located in the lower lip, the basal cell carcinoma is more common in the upper lip. The incidence of lip cancer in males is much high than in females. The etiopathogenesis of these lesions is connected with exposure to sun, smoking, genetics predisposition (mutation of the p53 suppressor factor) and with the evolution of precancerous lesions (radiodermatitis, chronic cheilitis, xeroderma pigmentosum). Some Authors emphasized the viral etiopathogenesis: HPV16, HPV24, HSV1, HSV2. The treatment of lip carcinoma is surgical: excision and reconstruction. The numerous reconstructive techniques are mostly the cutaneous local sliding flaps and the rotation flaps. The lip reconstruction require a remarkable diligence for preserve, as much possible, the shape and functions of lip. The Authors report their experience about the surgical treatment of 19 patients with lip carcinoma (16 spinous cell carcinomas, 3 basal cell carcinomas) and describe the main surgical reconstructive techniques to preserve the feeding, phonation and mimic expression.

Aged↗
PubMed2003

Continuing validity of pectoralis major muscle flap 25 years after its first application.

Surgical treatment of malignant cervico-facial tumours often includes vast demolition of mucosal, cutaneous, muscle and bone tissues, requiring immediate repair of the extensive loss of substance with reconstructive pedicled or revascularised free flaps. Still today, when it is not necessary to reconstruct the mandibular bone or in particular clinical situations as found in patients in whom microsurgery is contraindicated due to general conditions or in those cases of unsuccessful microsurgical flaps, use of the pedicled flaps is still indicated, particularly the myocutaneous flap of the major pectoral muscle described approximately 25 years ago, and quite rightly referred to as "work horse" or "spare wheel" of reconstructive surgery. Study population comprises 33 patients (27 male, 6 female, mean age: 61 years, range: 36-86) observed between 2000-2002. These patients were submitted to demolitive surgery on account of malignant cervico-facial neoplasias. The role of the major pectoral muscle pedicled flap is emphasised stressing that resection of the pedicle, even a few weeks after transplant, together with the subclavicular passage, may avoid the majority of the well-known functional and aesthetic problems related to this reparative technique.

Adult↗
PubMed2002

Apoptosis control and proliferation marker in human normal and neoplastic adrenocortical tissues.

We evaluated by immunohistochemistry the expression of the Bcl-2 and p53 proteins, as markers of apoptosis control, and of MIB-1, as a marker of cell proliferation, in a series of normal and neoplastic adrenocortical tissues. The specimens were 13 normal adrenals, 13 aldosterone-producing adenomas, 13 non-functioning adenomas and 16 carcinomas. Results were calculated as percentage of immunostained cells by using specific antibodies. No p53 protein was detected in any of the adrenocortical adenomas (functioning and non functioning) or normal adrenals, while p53 was overexpressed in 15 out of 16 carcinomas. In particular, 10 adrenal cancer specimens (62.5%) showed strong staining in a high percentage (range 10-50%) of the malignant cells. The percentage of Bcl-2 positive cells was higher (P<0.05 or less) in non-functioning adenomas (8.1+/-1.9%) and in carcinomas (14.9+/-5.6%) than in normals (2.9+/-0.9%) and aldosterone-producing adenomas (5.3+/-1.3%) since four specimens of the non-functioning adenomas-group (30.7%) and six of the carcinomas-group (37.5%) showed over 10% positivity (cut-off for normal values, set at 90th percentile of our controls). MIB-1 positivity was 0.50+/-0.36% in normals, 0.54+/-0.08% in non-functioning adenomas and 0.54+/-0.08% in aldosterone-producing adenomas. MIB-1 was expressed in all carcinomas with values (13.7+/-3.1%) significantly (P<0.0006) higher than in the other groups. In conclusion, the present data indicate that the apoptosis control and proliferation activity evaluated by the p53 and MIB-1 proteins are impaired in adrenal carcinomas but preserved in adenomas, independently of their functional status. Therefore, these immunohistochemical markers, overexpressed in carcinomas only, may be useful in the diagnosis of malignancy in adrenocortical tumours. Whether Bcl-2 positivity found in some carcinomas and non-functioning adenomas may constitute, in the latter, a negative prognostic marker is still unknown.

Adenocarcinoma↗
PubMed2002

Cell division cycle control in embryonal and alveolar rhabdomyosarcomas.

In this study, we investigated the mRNA level of several genes involved in cell cycle regulation in alveolar (ARMS) and embryonal rhabdomyosarcomas (ERMS). p21(Cip1), Cyclin D1, Cyclin D2, Cyclin D3, CDK2, and CDK4 were evaluated by RT-PCR. All (13 out of 13) ERMS expressed the p21(Cip1) gene compared with only 40% (4 out of 10) of the ARMS. Moreover, the amount of p21(Cip1) mRNA was noticeably higher in the ERMS samples than in the positive ARMS specimens. p27(Kip1) protein were analysed by immunohistochemical and immunoblotting. A noticeable difference was observed, in that ERMS had higher amounts of the cell cycle inhibitor compared with the ARMS. Finally, treatment of two rhabdomyosarcoma cell lines, RH-30 and RD, with butyrate, resulted in complete growth inhibition and in the upregulation of the p21(Cip1) and p27(Kip1) levels. Our results demonstrate that ERMS have a much higher level of p27(Kip1) and p21(Cip1) than the alveolar types, explaining, at least in part, the distinct features and outcomes (i.e. a poor prognosis of the alveolar type) of the two forms of this childhood solid cancer. Moreover, the data on butyrate-treated cell lines suggest that the two genes are potential novel therapeutic targets for the treatment of rhabdomyosarcomas.

CDC2-CDC28 Kinases↗
PubMed2002

Angiogenesis in human normal and pathologic adrenal cortex.

The angiogenic phenotype of 13 normal adrenal glands (N), 13 aldosterone-producing adenomas (APA), 12 cortisol-producing adenomas (CPA), 13 nonfunctioning adrenal cortical adenomas (NFA), and 13 adrenal cortical carcinomas (CA) was investigated. Intratumoral vascular density was explored by CD34, a marker of endothelial cells, and the angiogenic status was investigated by vascular endothelial growth factor (VEGF) expression, an important angiogenic factor expressed by tumoral cells. Vascular density, quantified as the number of vessels per square millimeter, was significantly lower (P < 0.0001) in CA (110.3 +/- 27.8) than in N (336.6 +/- 14.5), APA (322.8 +/- 19.1), CPA (288.5 +/- 14.3), and NFA (274.2 +/- 19.8). VEGF expression, calculated as the percentage of positive cells, was significantly greater (P < 0.0001) in CA (85.3 +/- 2.1) than in APA (56.5 +/- 7.5), CPA (38.5 +/- 7.0), N (33.1 +/- 6.1), and NFA (0.76 +/- 0.6). In APA, a negative relation between CD34 and plasma renin activity (P < 0.0002) and a positive association between CD34 and aldosterone levels (P < 0.05) was found. In conclusion, the angiogenic phenotype of CA is characterized by VEGF overexpression but low vascularization, a finding suggesting a dissociation between angiogenic potential and neoangiogenic capabilities of these tumors. The lack of VEGF expression in NFA and the close association between angiogenesis and functional status in APA also suggest a possible influence of the angiogenic phenotype on hormonal secretion of these endocrine tumors.

Adenoma↗
PubMed2001

Blocking caspase-activated apoptosis improves contractility in failing myocardium.

Cardiac myocyte apoptosis has been demonstrated in end-stage failing human hearts. The therapeutic utility of blocking apoptosis in congestive heart failure (CHF) has not been elucidated. This study investigated the role of caspase activation in cardiac contractility and sarcomere organization in the development of CHF. In a rabbit model of heart failure obtained by rapid ventricular pacing, we demonstrate, using in vivo transcoronary adenovirus-mediated gene delivery of the potent caspase inhibitor p35, that caspase activation is associated with a reduction in contractile force of failing myocytes by destroying sarcomeric structure. In this animal model gene transfer of p35 prevented the rise in caspase 3 activity and DNA-histone formation. Genetically manipulated hearts expressing p35 had a significant improvement in left ventricular pressure rise (+dp/dt), decreased end-diastolic chamber pressure (LVEDP), and the development of heart failure was delayed. To better understand this benefit, we examined the effects of caspase 3 on cardiomyocyte dysfunction in vitro. Microinjection of activated caspase 3 into the cytoplasm of intact myocytes induced sarcomeric disorganization and reduced contractility of the cells. These results demonstrate a direct impact of caspases on cardiac function and may lead to novel therapeutic strategies via antiapoptotic regimens.

Adenoviridae↗
PubMed2001

Gene transfer of heterologous G protein-coupled receptors to cardiomyocytes: differential effects on contractility.

In heart failure, reduced cardiac contractility is accompanied by blunted cAMP responses to beta-adrenergic stimulation. Parathyroid hormone (PTH)-related peptide and arginine vasopressin are released from the myocardium in response to increased wall stress but do not stimulate contractility or adenylyl cyclase at physiological concentrations. To bypass the defective beta-adrenergic signaling cascade, recombinant P1 PTH/PTH-related peptide receptors (rPTH1-Rs) and V(2) vasopressin receptors (rV(2)-Rs), which are normally not expressed in the myocardium and which are both strongly coupled to adenylyl cyclase, and recombinant beta(2)-adrenergic receptors (rbeta(2)-ARs) were overexpressed in cardiomyocytes by viral gene transfer. The capacity of endogenous hormones to increase contractility via the heterologous, recombinant receptors was compared. Whereas V(2)-Rs are uniquely coupled to Gs, PTH1-Rs and beta(2)-ARs are also coupled to other G proteins. Gene transfer of rPTH1-Rs or rbeta(2)-ARs to adult cardiomyocytes resulted in maximally increased basal contractility, which could not be further stimulated by adding receptor agonists. Agonists at rPTH1-Rs induced increased cAMP formation and phospholipase C activity. In contrast, healthy or failing rV(2)-R-expressing cardiomyocytes showed unaltered basal contractility. Their contractility and cAMP formation increased only at agonist exposure, which did not activate phospholipase C. In summary, we found that gene transfer of PTH1-Rs to cardiomyocytes results in constitutive activity of the transgene, as does that of beta(2)-ARS: In the absence of receptor agonists, rPTH1-Rs and rbeta(2)-ARs increase basal contractility, coupling to 2 G proteins simultaneously. In contrast, rV(2)-Rs are uniquely coupled to Gs and are not constitutively active, retaining their property to be activated exclusively on agonist stimulation. Therefore, gene transfer of V(2)-Rs might be more suited to test the effects of cAMP-stimulating receptors in heart failure than that of PTH1-Rs or beta(2)-ARS:

Adenoviridae↗
PubMed2001

A new human chromogranin 'A' immunoradiometric assay for the diagnosis of neuroendocrine tumours.

We investigated whether plasma chromogranin A (CgA), measured by a new immunoradiometric assay, may be a sensitive and specific marker of phaeochromocytoma and of other neuroendocrine tumours. This study involved 121 patients of whom 20 with phaeochromocytoma, 28 with other neuroendocrine tumours (19 gastroenteropancreatic tumors, 3 medullary thyroid and 6 small cell lung carcinomas), 25 with solid nonfunctioning adrenocortical tumours and 48 with essential hypertension. In addition, 130 normal subjects were taken as controls. Plasma catecholamines were measured by using high-performance liquid chromatography, and CgA by a two-site sandwich immunoradiometric assay involving monoclonal antibodies raised against the unprocessed central domain (145-245) of human CgA. Plasma CgA in controls (49.0 +/- 3.1 ng ml(-1), mean +/- SE) and in essential hypertensives (50.8 +/- 3.5 ng ml(-1)) was lower (P< 0.0001) than in adrenocortical tumours (91.8 +/- 13.2 ng ml(-1)), in phaeochromocytomas (254 +/- 49 ng ml(-1)) and in patients with other neuroendocrine tumours (469 +/- 84 ng ml(-1)). Plasma CgA and catecholamines identified 13 and 18 out of 20 phaeochromocytomas with sensitivity of 65% and 90%, respectively. Combined measurement of both markers improved sensitivity up to 100%. In the other neuroendocrine tumours, CgA was abnormal in 23/28 cases (sensitivity 82%) and in 6 it was the only circulating marker of disease. In gastroenteropancreatic tumours, CgA measurement identified all cases (sensitivity 100%). Specificity of CgA in patients with essential hypertension was 98%. In conclusion, CgA determination showed high sensitivity in identifying gastroenteropancreatic tumours and, in association with catecholamines, in detecting patients with phaeochromocytoma. CgA sometimes appeared to be the only circulating marker of disease. Since the specificity of CgA proved to be excellent, this assay may be useful for diagnosis both of functioning and non-functioning neuroendocrine tumours.

Adolescent↗
PubMed2001

Digestive neuroendocrine tumours: diagnosis and treatment in Italy. A survey by the Oncology Study Section of the Italian Society of Gastroenterology (SIGE).

BACKGROUND: New insights in the diagnosis and treatment of digestive neuroendocrine tumours have prompted a renewed interest in these rare and complex diseases. AIM: To establish how many new cases of digestive neuroendocrine tumours were diagnosed, and how they were treated, at gastroenterological centres across Italy during a two-year period (1997-1998). METHODS: The 12 centres taking part filled in a data collection form reporting type of tumour, methods of diagnosis and therapeutic strategies adopted in each case. Data were collected and analysed by the authors of the present report. RESULTS: Data refer to 98 patients, 22 with functioning and 76 with non-functioning digestive neuroendocrine tumours [50 carcinoids, 48 pancreatic endocrine tumour syndromes]. Primary tumours were localised in 96% (38% with metastases) of non-functioning and 81% (50% with metastases) of functioning tumours. These were surgically removed in >80% of patients in both groups. Somatostatin analogue treatment, with or without interferon, was administered in 35% of patients, while chemotherapy was used in 9% and 23% of functioning and non-functioning tumours, respectively. The imaging study always included a computed tomography scan (20% helical computed tomography). Magnetic resonance and somatostatin receptor scintigraphy were also performed, the former in 41% and 21% of the two (functioning and non-functioning tumour) groups, the latter in 45% and 30%. CONCLUSIONS: The number of functioning digestive neuroendocrine tumours reported was lower than expected. Surgery plays a major role in the treatment of these tumours in all centres. Overall, in only a small number of patients was a multidisciplinary approach applied.

Adolescent↗
PubMed2001

Effect of Fusarium, Paecilomyces and Trichoderma formulations against aphid Schizaphis graminum.

Fungal strains belonging to the genera Fusarium, Paecilomyces and Trichoderma were tested in vitro in order to study their effects against Schizaphis graminum, one of the major pests of cereal crops around the world. Biological assays were performed using a solid formulation that was obtained from fungal cultures grown on rice and then finely ground (<0.2 mm). The occurrence of toxic secondary metabolites (fumonisin B1 and beauvericin) produced by these fungi was also investigated. In each experiment, three groups of aphids: 15-hour old larvae, 5-day old nymphs with wing buds and wingless morphs were treated with a suspension of a fungal formulation. Some strains belonging to the genera Fusarium and Trichoderma significantly controlled the specimens of the three groups of S. graminum. The F proliferatum strain ITEM 1407, producing a high level of fumonisin B1 in the culture (1250 microg/g), and F larvarum strain ITEM 2139 had high insecticidal activity (>60%) within 10 minutes after application. As F. larvarum ITEM 2139 did not produce metabolites toxic to mammals, it might be a good candidate as a biocontrol agent of S. graminum in the field.

Animals↗
PubMed2001

The use of a synthetic antigen for the serological diagnosis of human trichinellosis.

Hosts infected with Trichinella produce antibodies specific for an epitope common to the TSL-1 family antigens. This epitope contained uncommon terminal 3, 6-dideoxy-D-arabinohexose (so called tyvelose) residues. The disaccharide moiety was synthesized and an immunodiagnostic assay was developed, which was specific and sensitive in swine trichinellosis. We aimed to verify the specificity and sensitivity of this immunodiagnostic test in human trichinellosis. 15 sera from normal subjects, 12 from patients with other parasitic diseases and 50 from trichinellosis patients were tested. Indirect enzyme linked immunosorbent assay (ELISA) for specific IgG and an amplified ELISA for specific IgE were performed using beta-tyvelose-GalNAc-bovine serum albumin (BSA) disaccharide conjugate or T. spiralis muscle larvae excretory/secretory (E/S) products, as antigens. Neither control sera nor other parasitic infection sera resulted positive both for IgG and IgE when synthetic or E/S antigens were used. In trichinellosis patient sera, specific IgG were present in 100% of cases, irrespective of the antigen used, but whereas specific IgE were detected in 78% using E/S antigens, a 100% positivity rate was obtained, using the beta-tyvelose-BSA conjugate.

Antibodies, Helminth↗
PubMed2001

Experimental trichinellosis in fallow-deer (Dama dama L.).

Herbivora can play a very important role in spreading trichinellosis, as showed by the massive epidemics in man, caused by the consumption of horse meat in the last years. In this context, the present study has been undertaken to verify, through an experimental infection, the susceptibility, together with other biological parameters, of fallow-deer to Trichinella infection. The four animals, 8-9 months of age and 18-25 Kg body weight, were orally infected with low doses of Trichinella britovi and T. pseudospiralis (2,000 larvae/animal). After day 30 p.i., the animals were necropsied and, using artificial digestion methods, larval burden of Trichinella in muscle tissues was determined. Histopathological, serological (IgG monoclonal blocking ELISA) and biochemical data were assessed during the experiment. The results showed the susceptibility of fallow-deer to T. britovi and T. pseudospiralis infection; under the same inoculum size, the number of larvae/g was higher in group infected with T. britovi. The animals showed a higher immunological response to T. pseudospiralis infection. The results are discussed.

Animals↗
PubMed2001

Trichinella spp. in ostrich meat: a public health risk?

In the present work the biological behaviour of T. spiralis and T. pseudospiralis in ostriches is reported. Oral infections were performed in eight ostriches with two infective doses (10,000 and 80,000 larvae) for each species of Trichinella. On day 0, 30 and 60 p.i. blood samples were collected to assay the serum changes concerning specific muscle enzyme activities and total proteins. The immunological study, to determine specific IgG in sera, was conducted employing a monoclonal blocking ELISA. From the carcasses of sacrificed animals, samples of various muscle tissues were examined by the digestion method and by standard histopathologic procedures. The study showed a low susceptibility of the ostriches to T. pseudospiralis; preferential sites of larval distribution were muscle tissues of the legs. T. spiralis could be found in muscle tissues only when a high number of larvae were inoculated. Immunological reactivity was found only in animals infected with higher doses of T. pseudospiralis.

Animals↗
PubMed2001

Susceptibility of nutria (Myocastor coypus) to Trichinella infection: biological aspects.

Experimental infections with three different species of Trichinella in nutria in order to evaluate the susceptibility and the role of these rodents in the spreading of parasitosis in nature were carried out. The nutria is present in many italian wet areas and its distribution is expanding. The nutria meat is utilized as food in different countries and is retained responsible for trichinellosis in man. Two groups of ten animals were infected per os with 500 and 5,000 (n. 10) infective larvae of T. britovi; an additional study was arranged with two groups of animals infected with 5,000 larvae of T. spiralis and T. pseudospiralis, respectively. After 45 days, all animals were slaughtered and samples of different muscles were processed by standard artificial digestion and by routine histological methods. Serological investigations (specific IgG) have been carried out on sera samples by employing a monoclonal blocking ELISA. The animals showed a significant susceptibility to the infection with all species of tested Trichinella and immunological reactivity. Data obtained are discussed.

Animals↗
PubMed2001

Effects of sublethal ammonia exposure on swimming performance in rainbow trout (Oncorhynchus mykiss).

Adult trout Oncorhynchus mykiss fitted with a dorsal aortic catheter were exposed to 288+/-15 micromol l(-1) (mean +/- S.E.M.) total ammonia for 24h in water at a pH of 8.39+/-0.02, while swimming at a speed equivalent to 0.75 bodylengths s(-1) (BLs(-1)) in a Brett-type tunnel respirometer. The fish were then exposed to stepwise increments in swimming speed (0.25 BLs(-1) every 30 min) until exhaustion. Measurements of oxygen uptake (M(O2)) and plasma total ammonia levels and pH were made at each speed. Control trout were treated identically but without exposure to ammonia. Ammonia exposure caused an increase in plasma total ammonia level to 436+/-34 micromol l(-1), compared to 183+/-30 micromol l(-1)in control animals (N=6). A significant reduction in total plasma ammonia level was found in both groups during exercise, despite a large negative concentration gradient in those exposed to an elevated concentration of ammonia in water, which may indicate an active excretory process. The overall increase in plasma ammonia levels in exposed trout was associated with a significant reduction in critical swimming speed (U(crit)) to 1.61+/-0.17BL s(-1) from 2.23+/-0.15BL s(-1) in control animals. Ammonia-exposed trout had a significantly higher maintenance metabolic rate (MMR) than control fish, when estimated as the y-intercept of the relationship between swimming speed and M(O2). Active metabolic rate (AMR, maximum M(O2) as measured at U(crit)) was significantly lower in ammonia-exposed animals, leading to a profound reduction in factorial aerobic scope (AMR/MMR). Reduced U(crit) was also linked to a reduction in maximum tailbeat frequency. Calculation of membrane potentials (E(M)) in the white muscle of fish swum to U(crit) revealed a significant partial depolarisation of white muscle in ammonia-exposed fish. This may have prevented white muscle recruitment and contributed to the reduced maximum tailbeat frequency and overall impairment of swimming performance in the ammonia-exposed fish.

Ammonia↗
PubMed2000

Plasma levels of amyloid beta 40 and 42 are independent from ApoE genotype and mental retardation in Down syndrome.

In Down syndrome (DS) brain an early, selective accumulation of amyloid beta (Abeta) peptides ending at residue 42 (Abeta42) occurs. Whether this event depends on an altered processing of amyloid beta precursor protein (APP) or on defective clearance is uncertain. To investigate this issue, we measured Abeta species 40 and 42 in plasma from 61 patients with DS, 77 age-matched normal controls, and 55 mentally retarded subjects without chromosomal abnormalities. The Abeta 40 and 42 plasma levels were then correlated with apolipoprotein E (apoE) genotypes in all groups of cases, and with I. Q. and Mini Mental Status Examination values in DS subjects. Both Abeta species were significantly elevated in DS compared to control groups, and the extent of their increase reflects that expected from APP gene overexpression. Plasma levels of Abeta 40 and 42 did not correlate with apoE genotypes in DS and control cases, and with the extent of mental retardation in DS subjects. The results indicate that accumulation and clearance of plasma and cerebral Abeta are regulated by different and independent factors.

Adolescent↗