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Biomedical subjects

W Mantovani

Publications and source records attributed to W Mantovani.

At least 19 recordsLinked to original sources

Predictive factors of efficacy of the somatostatin analogue octreotide as first line therapy for advanced pancreatic endocrine carcinoma.

About 40% of nonfunctioning pancreatic endocrine carcinomas (NF-PEC) cannot be cured by surgery due to advanced stage disease. Somatostatin analogues have been proposed as first line therapy in these cases. We performed a prospective phase IV study to assess the efficacy of octreotide in advanced NF-PEC and identify factors predictive of response to therapy. Twenty-one consecutive patients with octreoscan-positive advanced-stage well-differentiated NF-PEC were treated with long-acting release octreotide 20 mg i.m. at diagnosis. The immunohistochemical expression of somatostatin receptor 2 (SSTR2) and the quantitative mRNA analysis of SSTR2 and SSTR5 were assessed in 12 tumours. The tumour proliferative fraction was assessed by immunohistochemistry for Ki-67. Eight patients (38%) had stable disease (SD) after a median follow-up of 49.5 months. Thirteen patients (62%) developed progression after a median of 18 months. Tumour progression correlated with a proliferative index>or=5% (P=0.016), weight loss (P=0.006) and absence of abdominal pain (P=0.003) at diagnosis. Other clinical (age, gender and primary tumour resection) or pathological parameters (site, size and liver metastasis) lacked significant correlation with tumour progression. No difference in the amount of SSTR2 mRNA and protein or SSTR5 mRNA was found between tumours that were stable (n=5) and seven tumours that progressed (n=7). Treatment with long-acting release octreotide was associated with stabilization of disease and a good quality of life in 38% of patients. A Ki-67 index>or=5% and/or the presence of weight loss may justify more aggressive therapy without waiting for radiologically proven progression of disease.

Aged↗

Levels of F2-isoprostanes in systemic sclerosis: correlation with clinical features.

OBJECTIVE: Oxidative stress may be one of the important complex pathogenetic mechanisms that lead to damage in scleroderma; free radicals may provoke endothelial injury, fibroblast proliferation and fragmentation of autoantigens favouring induction of autoantibodies. The present study investigates the oxidant status in scleroderma patients by measuring the urinary concentration of 8-isoprostaglandin-F2alpha, an F2-isoprostane, and a product of free radical-mediated peroxidation of arachidonic acid. METHODS: Forty-three scleroderma patients (42 women and 1 man, mean age 54.1 yr, mean disease duration 9.0 yr) underwent clinical evaluation and instrumental investigations in order to assess skin, vascular, lung and heart involvement. Von Willebrand factor was evaluated as marker of vascular dysfunction in 36 out of the 43 cases. The urinary level of 8-isoprostaglandin-F2alpha was measured in all scleroderma patients and in the 43 age- and sex-matched healthy controls. RESULTS: Urinary levels of 8-isoprostaglandin-F2alpha were higher in scleroderma patients than in the healthy control group (341.7 vs 147.6 pg/mg creatinine; P < 0.001). Values of 8-isoprostaglandin-F2alpha were strongly correlated with the nailfold videocapillaroscopy pattern and lung involvement (P = 0.002 and 0.003, respectively), showing increasing levels with the progression of pulmonary severity. Correlation between 8-isoprostaglandin-F2alpha level and von Willebrand factor narrowly failed to reach statistical significance (P = 0.05). There was no correlation between 8-isoprostaglandin-F2alpha concentration and disease activity, vascular, skin and heart involvement, disease pattern or autoantibody profile. CONCLUSIONS: Our study further supports the role of oxidant stress in the pathogenesis of scleroderma, showing a strong correlation between a marker of free radical damage with both the severity of lung involvement and the videocapillaroscopic patterns.

Adult↗

Role of unlabelled somatostatin analogues in the prevention of complications after elective pancreatic and peripancreatic surgery: a critical review.

Although studies on the use of the somatostatin analogues in the elective pancreatic surgery are mostly prospective, double blind and randomised, the results are contradictory and not univocally interpretable. Through the examination of all randomised perspective works published on this subject, a critical interpretation is attempted which may give relevant suggestions for further studies. A new clinical, randomised, double blind and multicentric prospective trial should take into proper consideration even the changes which have occurred in the care of the patients. Over the years a significant decrease of postoperative hospital stay and a deeper awareness of the medical expenses have been observed. Moreover, since the drug has a potential advantage on specific pancreatic complications, only these must be considered among the end points of the study and the population studied will be limited exclusively to patients who underwent resection of the pancreatic head or of the periampullar region because of neoplastic disease. Finally, the selection of the centres that enrol the patients must be considered, since the expertise of each operator or of the team, affects, as an independent variable, both morbidity and mortality.

Double-Blind Method↗

Mortality and recruitment of trees in a secondary montane rain forest in southeastern Brazil.

Mortality and recruitment rates were obtained for tree species over a 5.6 year period in a 1-ha fragment of secondary montane rain forest in Southeastern Brazil. All plants with a diameter at breast height (dbh) > or = 8 cm were sampled in 1989-1990 and 1995. There was an increase from 90 to 96 species, and 669 ind./ha to 749 ind./ha over the period. The mortality rate of 1.67%/yr was similar to findings for other forests, while recruitment of 3.46%/yr was the highest rate reported. Both mortality and recruitment were significantly higher in the smaller dbh classes. Recruitment was higher among rare species, and the relatively slow-growing species had significantly higher mortality rates. Differences between species dynamics were marked. Species with high values of lambda were mainly early successional and understorey trees but some understorey species also suffered a marked population decline. The classification system of species in response to light which divides understorey species into "partial shade-bearers" and "shade-bearers" groups showed to be the most suitable to the obtained results. The results suggest that this forest is undergoing a process of recovery from past disturbance.

Brazil↗

High recurrence rate after atypical resection for pancreatic metastases from renal cell carcinoma.

BACKGROUND: Pancreatic metastases from renal cell carcinoma are rare but highly resectable. The aim of this study was to review a series of patients with this condition. METHODS: The study involved 22 consecutive patients with histologically proven pancreatic metastases from renal cell cancer. RESULTS: Seventeen of the 22 patients had surgery. No patient died but eight of the 17 patients had a postoperative complication. Median follow-up was 33 (range 1-96) months. The 24- and 60-month survival probabilities were 0.84 and 0.53 respectively. Five patients who did not undergo surgery had 24- and 60-month survival probabilities of 0.53 and 0.26 respectively. The difference between the two groups was significant (P = 0.040). CONCLUSION: Despite the slow development of these secondaries and their well encapsulated morphology, the high rate of recurrence after limited resection suggests that radical resection should be recommended.

Adult↗

Carcinoma of pancreatic body and tail: are there improvements in diagnosis and treatment modalities over the past decade?

BACKGROUND AND AIM OF STUDY: The aim of the present study is to assess whether or not there has been improvement in the therapeutic strategy for body-tail pancreatic carcinoma over the past decade. PATIENTS AND METHODS: A total of 215 patients suffering from cytologically and histologically documented ductal carcinoma in the pancreatic body-tail, observed from 1990 to 1999, were analysed. Changes in tumour stage at diagnosis, in the percentage of patients treated surgically, in resectability rates and in the use of anticancer therapies over the years were sought. Survival curves were evaluated in relation to the treatments adopted. RESULTS: Over the 10-year period, no significant differences were observed with respect to the stage at diagnosis, resectability or type of surgery adopted. There was a significant increase in the percentage of unoperated patients (p < 0.0001) and, as expected, in the percentages of patients submitted to chemo- and/or radiotherapy (p < 0.0001). With the sole exception of tumour stage in the case of patients undergoing radiotherapy, a comparison between groups revealed no element of patient selection bias other than time. The survival of patients undergoing chemotherapy is significantly better, also at multivariate analysis, than that of patients not undergoing such therapy (13 vs. 5.8 months; p < 0.0001). CONCLUSIONS: There has been no change over the years in the direction of earlier diagnosis and the prognosis remains distinctly poor. More extensive use of anticancer therapies, however, has led to a significant increase in median survival. Radical resection, when possible, assures the longest survival.

Carcinoma, Ductal, Breast↗

The soil seed bank during Atlantic Forest regeneration in Southeast Brazil.

A survey was conducted to determine the density and species composition of viable seeds buried in four stands of a tropical montane forest at Parque Estadual Intervales, Brazil. The objective was to understand: (1) how numbers and composition of the soil seed bank change as the forest regrows, and (2) how such changes affect the species available for regeneration if forests of different ages are cut down. In each forest stand (5, 18, 27-yr-old and a mature forest), 57 soil samples were collected (0-2.5 and 2.5-5 cm deep). Viable seed density of herbaceous species ranged between 11,003 seeds. m-2 (5-yr-old vegetation) and 482 (mature forest), and between 25 (5-yr-old vegetation) and 389 seeds. m-2 (mature forest) for woody plant species in the 0-5 cm soil layer, suggesting a decrease in seed stocks in the course of forest regeneration. Seeds buried in the 0-2.5 cm soil layer represented between 56.9% and 67.4% of all viable seeds. Most of the viable seeds belonged to weeds of Asteraceae, Poaceae, Malvaceae and Solanaceae. The results provide evidence that, in forests of different ages, the soil does not store seeds of the same key ecological groups involved in the regeneration of Atlantic forest. Allochthonous seeds from remaining patches of forest, as well as their vertebrate dispersers, are needed for forest regeneration since the soil seed bank does not store large seeds of shade-tolerant species.

Brazil↗

Vegetation structure in cerrado physiognomies in south-eastern Brazil.

We studied three cerrado physiognomies (campo cerrado, a savanna woodland; cerrado sensu stricto, a woodland; and cerradão, a tall woodland) in a reserve with 1,225 ha, in Santa Rita do Passa-Quatro (21 degrees 36-38'S and 47 degrees 36-39'W), São Paulo State, South-eastern Brazil, to compare plant communities structure. As descriptors of the vegetation structure, we used richness, density, basal area, cylindrical volume, and diversity. Ten 40 m2 quadrats were placed randomly in each physiognomy, in which we sampled the woody plants with stem diameter equal or larger than 1 cm (woody component), and ten 2.5 m2 quadrats, in which we sampled the woody plants with stem diameter smaller than 1 cm and all the non-woody individuals (herbaceous component). In the woody component, we found significant differences among the physiognomies for richness, density and cylindrical volume. Cylindrical volume increased from campo cerrado to cerradão, but richness and density were higher in cerrado sensu stricto. In the herbaceous component, we detected differences for all variables, which were higher in the savanna physiognomies, campo cerrado and cerrado sensu stricto, than in the forest physiognomy, cerradão. Cylindrical volume was the best variable to distinguish the physiognomies. Floristic similarity followed the campo cerrado-cerrado sensu stricto-cerradão gradient, and beta diversity was higher in the herbaceous component.

Brazil↗

Lack of association with spondyloarthritis and HLA-B27 in Italian patients with Whipple's disease.

OBJECTIVE: To examine consecutive patients with Whipple's disease (WD) for the full clinical spectrum of spondyloarthritis. METHODS: Nine consecutive patients, 8 men, 1 woman, with WD were clinically evaluated and examined for clinical and radiological manifestations of spondyloarthritis by 2 rheumatologists with special interest in spondyloarthritis. The mean age of the patients at the time of study and at the time of their initial diagnosis of WD by duodenal biopsy was 62.4 years (range 42-71) and 54.4 years (range 40-62), respectively. Each patient had an anteroposterior radiographic view of the pelvis and also had HLA typing for class I and II alleles. Pelvis radiographs were read blindly for evidence of sacroiliitis. RESULTS: All but one patient had rheumatologic manifestations related to WD. The mean interval between the onset of these symptoms and the diagnosis of WD was 6.1 years (range 1-15). One had recurrent polyarthritis, 1 recurrent oligoarthritis, 3 recurrent monoarthritis, 2 recurrent synovitis with pitting edema of the dorsum of hands and/or feet, and 1 isolated De Quervain's tenosynovitis. Of the 5 patients with arthritis, 3 also had episodes of swelling with pitting edema over the dorsum of hands and/or feet together with flexor digit tenosynovitis, 2 also had olecranon bursitis, and 1 tibial tenosynovitis. No patient had clinical or radiological manifestations of spondyloarthritis. None had the HLA-B27. CONCLUSION: In Italian Caucasian patients with WD there was no association with spondyloarthritis and HLA-B27.

Adult↗

Reproductive phenological patterns of cerrado plant species at the Pé-de-Gigante Reserve (Santa Rita do Passa Quatro, SP, Brazil): a comparison between the herbaceous and woody floras.

A natural vegetation area, with 1269 ha, composed mainly by cerrado, located at Santa Rita do Passa Quatro Municipality, São Paulo State, southeastern Brazil (21 degrees 36-39'S, 47 degrees 36-38'W), was studied. From September 1995 to February 1997, a floristic survey was carried out, when all vascular plant species at reproductive stage were collected. The flowering and fruiting patterns of the community were studied, comparing the herbaceous and the woody species. In the herbaceous component, 239 species were found and, in the woody one, 108 species. The woody species flowered mainly at the beginning of the rainy season, while the herbaceous ones produced flowers generally at the end of that season. The proportion of anemo and autochorous species was greater in the herbaceous component. The zoochorous ones, on the contrary, were more frequent in the woody component. At the dry season, when their dispersion is more efficient, the proportion of anemo and autochorous species producing fruits was higher. During the rainy season, when their fruits become attractive for longer time, the zoochorous species fruited more intensely.

Brazil↗

HLA-DRB1 alleles associated with rheumatoid arthritis in Northern Italy: correlation with disease severity.

The aim of the study was to evaluate the relationship between the presence of the 'rheumatoid epitope', defined by a sequence motif in the HLA-DRB1 alleles, rheumatoid factor and disease severity in Northern Italian patients with rheumatoid arthritis (RA). Twenty-nine DR4-positive and 57 DR4-negative RA patients were studied. Each DR4-positive patient was matched with two DR4-negative controls of similar disease duration and sex. HLA-DRB1 alleles were determined in the 86 patients and 351 controls from the same geographical area. The patients were retrospectively evaluated for extra-articular features (EAF) and radiographic damage. The rheumatoid epitope was expressed in 45% of patients. No significant differences in the presence of rheumatoid factor, EAF and articular damage were observed between patients with no, one or two doses of epitope. However, the patients encoding the epitope by an HLA-DR4 allele had a higher number of eroded joints and a higher Larsen score compared to those without the epitope. No differences were present between patients expressing HLA-DRB1*01 alleles and those lacking the rheumatoid epitope. Even in the absence of expression of the rheumatoid epitope, seropositive patients had more EAF and more erosive disease compared to those who were seronegative. Even if most Northern Italian RA patients do not express the rheumatoid epitope, the radiological severity of disease is associated with HLA-DRB1*04 alleles.

Aged↗

["Black adenoma" associated with medullary nodular hyperplasia in the ipsilateral adrenal gland. Case report and review of the literature regarding "mixed" cortico-medullary pathology].

BACKGROUND: Pigmented or "black" cortical adenoma is a rare variant of the compact or eosinophilic cell type of adrenal gland cortical adenoma. Usually it is non functioning so representing an incidental finding at autopsy, but rare cases producing Cushing's syndrome or hyperaldosteronism have been reported. The simultaneous occurrence of a cortical adenoma and pheochromocytoma in the ipsilateral adrenal gland is an extremely rare event, which has been so far described only seven times with the cortical adenoma always being of the usual yellow or clear cell type. So far no case of "black adenoma" associated with a proliferative condition of the ipsilateral adrenal medulla has ben described. CASE REPORT: A case of functioning pigmented ("black") cortical adenoma in a male patient affected by Cushing's syndrome associated with asymptomatic medullary nodular hyperplasia in the ipsilateral adrenal gland is described. The results of light microscopy, histochemistry, immunohistochemistry, and electron microscopy studies are presented. It is worthy of note the finding of two types of pigment granules (lipofuscin type, neuromelanin type) observed at elecatron microscopy. CONCLUSIONS: The authors underline the difficulty of classifying adrenal medullary nodules and the arbitrarity usually adopted in separating nodular adrenal medullary hyperplasia from early neoplasia (pheochromocytoma). Thus nodular medullary hyperplasia in this case could also be interpreted as an early neoplastic condition. The case herein presented is the first report of a combined cortico-medullary proliferative process in which a "black" adenoma is involved.

Adrenal Cortex↗

N-myc amplification and cell proliferation rate in human neuroblastoma.

In neuroblastoma, N-myc amplification has been found to be strikingly associated with rapid tumour progression and poor prognosis. Recent studies have demonstrated that cell proliferative activity also significantly predicts the clinical outcome in patients with neuroblastoma. In order to define the correlation between N-myc amplification and cell proliferation rate, in the present investigation the two parameters were first assessed in 48 neuroblastoma tumours. N-myc amplification was evaluated in frozen specimens by Southern-blot analysis using the NB 19-21 probe and it was detected in nine patients. Cell proliferative activity was determined by measuring the AgNOR protein area in histological sections selectively stained by silver. The mean AgNOR protein area value of neuroblastomas with N-myc amplification (3.63 +/- 1.62 microns2) was not significantly different from that of neuroblastomas without N-myc amplification (2.46 +/- 1.57 microns2; P = 0.30). On the other hand, both N-myc amplification and AgNOR protein expression were found to be significantly related to the clinical outcome of the disease (P < 0.001 and P = 0.0143, respectively; median follow-up time = 47 months; range 18-106 months). In a second set of experiments, the relationship between N-myc amplification and cell proliferation rate was assessed in seven established human neuroblastoma cell lines. N-myc amplification was found to be completely independent of the population doubling time (DT), which, on the contrary, was strictly related to the quantitative expression of AgNOR protein (r = -0.947; P < 0.001). Altogether, the present results indicate that N-myc amplification and cell proliferation rate are not interrelated in neuroblastoma, each representing an independent biological parameter of cancer cells associated with the clinical behaviour of the disease.

Antigens, Nuclear↗

An 8-year follow-up of anti-insulin antibodies in diabetic children: relation to insulin autoantibodies, HLA type, beta-cell function, clinical course and type of insulin therapy.

In 105 children and adolescents with IDDM, insulin antibodies were detected as a percentage of radiolabelled insulin both at onset of disease and during the first 8 years of treatment. At diagnosis, 29 patients (27%) were insulin autoantibody positive (IAA+). An inverse relationship was found between IAA levels and age at diagnosis. No significant correlation was seen between IAA positivity and HLA antigens, while there was a negative correlation between IAA and C-peptide levels in the second year of the disease. The percentage of insulin antibody (IA) positive patients increased after insulin administration, with a maximum peak between the first and second year of the disease. The IA response to insulin therapy was similar in IAA+ and IAA- patients, while it was greater in younger children. No relationship was found between IA levels and haemoglobin A1c values, daily insulin requirement, HLA and early complications. No difference in either percentage of positivity or IA levels was seen in patients treated continually for the first 5 years of the disease with monocomponent porcine insulin or human insulin. A negative correlation was found between IA and C-peptide levels in the first and second years of the disease. In conclusion, we have shown that, even after many years of disease, neither IAA nor IA, induced in equal measures by current human insulin preparations, have significant effects on the clinical course of the disease.

Adolescent↗

Prevalence of psoriatic arthritis in Italian psoriatic patients.

OBJECTIVE: To evaluate the prevalence of psoriatic arthritis (PsA) in Italian patients with psoriasis and to compare the Moll and Wright criteria, the European Spondylarthropathy Study Group (ESSG) criteria, and Amor criteria when applied to this patient population. METHODS: We examined 205 unselected patients with psoriasis. The diagnosis of PsA was based upon the clinical experience of a rheumatologist. After, we tested these classification criteria. HLA class I and II antigens were also analyzed. RESULTS: Thirty-six percent (75) of psoriatic patients were considered by a clinical expert to have PsA. Moll and Wright criteria identified 46 patients (22%) with PsA; 49 patients (24%) were identified by ESSG criteria and Amor criteria; 12 patients identified by Amor criteria but not by ESSG criteria presented enthesitis or dactylitis; 10 patients identified by ESSG but not by Amor criteria had peripheral synovitis. In patients with peripheral arthritis and psoriasis, the evaluation of NSAID response was critical to fulfilling Amor criteria. However, it was not easy to retrospectively evaluate NSAID response using these criteria. The sensitivity was low for each of the 3 classification criteria (from 61 to 65%), whereas the specificity was high (from 99 to 100%). CONCLUSION: Our study confirms a high prevalence of PsA among an unselected population of Italian patients with psoriasis. Our data reveal the inadequacy of the existing criteria for PsA, including the ESSG criteria and Amor criteria for the classification of spondyloarthropathy.

Aged↗

[4 cases of Horton's temporal arteritis. Hypothesis on the possible correlations with rheumatic polymyalgia].

Giant cell arteritis (GCA) or temporal arteritis is an entity of unknown aetiology and uncertain autonomy for the close relationship with polymyalgia rheumatica (PMR). This work describes four patients with GCA alone. All patients had clinical and laboratoristic evidence of the disease and were treated with steroids. The distribution of HLA antigens showed an increased occurrence of DR4 and B8 antigens. Unfortunately, the small number of patients and the short period of observation don't allow to prove the exact nature of the link between GCA and PMR.

Aged↗