Nucleolin protein expression in cutaneous melanocytic lesions

Background:  Nucleolin is a major nucleolar argyrophilic protein involved in carcinogenesis. There are only few studies on its tissue expression in human cancer and none in melanoma. We aimed at exploring this protein and its prognostic impact in cutaneous melanocytic lesions.
Methods:  We studied 193 cases including benign, dysplastic and malignant melanocytic lesions. Nuclear positivity was evaluated by immunohistochemistry and quantified by automated image analysis.
Results:  Most dysplastic and malignant lesions showed high percentages of cells with abnormal patterns of nuclear positivity (Abn+N) consisting in multiple, irregular, positive dots (ID+) and a coarse, irregularly positive nucleoplasm (CNpl+) or both (ID+CNpl+). The patterns CNpl+ and/or ID+CNpl+ were never observed in benign lesions, in which ID+ were also virtually absent. Abn+N% was significantly lower in dysplastic nevi than in primary melanomas and metastases and in primary melanomas than in metastases (p < 0.05). Furthermore, Abn+N was the second powerful prognostic discriminator, after melanoma thickness, and a significantly lower survival was observed in vertical growth phase melanoma patients showing Abn+N in more than 50% of melanoma cells.
Conclusion:  An altered nuclear nucleolin expression seems to accompany melanoma progression. Further investigation on nucleolin functionality and subcellular trafficking could add information on its altered role in melanoma.     

Factors affecting aseptic loosening of 4750 total hip arthroplasties: multivariate survival analysis

Background  

Total hip arthroplasty is a successful surgery, that fails at a rate of approximately 10% at ten years from surgery. Causes for failure are mainly aseptic loosening of one or both components partially due to wear of articular surfaces and partially to design. The present analysis aimed to identify risk factors and quantify their effects on aseptic failure.     

Long-term Doppler echocardiographic evaluation of the right heart after major lung resections.

OBJECTIVE: The effects of major lung resections on cardiac function in the medium and long term have not been thoroughly evaluated. We have studied right heart function with serial Doppler echocardiography in patients undergoing lobectomy and pneumonectomy during 4 years of follow-up after surgery. METHODS: Thirty-six patients undergoing lobectomy and 15 receiving pneumonectomy were evaluated with one- and two-dimensional Doppler standard transthoracic echocardiography before surgery and 1 week, 3 months, 6 months, 1 year, and 4 years postoperatively. We have studied the right midventricular diastolic diameter (RVDD), the right ventricle free wall thickness, the tricuspid valve insufficiency (TVI) and regurgitation jet (TRJ), and the pulmonary artery systolic pressure (PASP). RESULTS: None of the patients died within the first postoperative year. After lobectomy there were no significant modifications of any variable at any time. RVDD progressively increased after pneumonectomy (26.5+/-2.2mm preoperatively vs 34.3+/-7.6 at 4 years; p<0.001). Four years after surgery all patients undergoing pneumonectomy had moderate TVI while only 55% of patients receiving lobectomy showed it (low grade in 50% and moderate in 5%). In this group of patients PASP increased from 26.1+/-2.6 mmHg preoperatively to 34.3+/-7.6 mmHg at 4 years (p<0.00001). CONCLUSIONS: Right ventricle modifications are clearly evident after pneumonectomy and even if they do not show a clear clinical impact they should not be neglected.     

Efficacy of piribedil as early combination to levodopa in patients with stable Parkinson's disease: a 6-month, randomized, placebo-controlled study.

Piribedil is a non-ergot D2/D3 agonist with a significant antagonist action on alpha2A and alpha2C adrenergic receptor subtypes. This double-blind placebo-controlled study was undertaken to confirm the efficacy of 150 mg/day piribedil po in improving motor symptoms of idiopathic Parkinson's disease (PD) in nonfluctuating patients insufficiently controlled by a stable daily dose of levodopa (L-dopa). Efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) III score as primary criterion over 4 months. A second comparison was planned at 6 months, after possible adjustment of L-dopa. At 4 months, the rate of response, defined as a 30% decrease from baseline on UPDRS III score, was significantly greater with piribedil compared with placebo (56.4% vs. 37.7%; P = 0.040). At 6 months, the better efficacy of piribedil was maintained (61.8% of responders vs. 39.6% on placebo; P = 0.020). The difference between groups on UPDRS III change from baseline reached statistical significance only at 6 months: -10.0 points in the piribedil group vs. -6.7 points in the placebo group (P = 0.037). Secondary end-points were not significantly different. The most frequently reported adverse events were gastrointestinal symptoms (27 of 61 patients in the piribedil group vs. 13 of 54 patients in the placebo group). In conclusion, a 6-month oral administration of 150 mg/day piribedil in combination with L-dopa is well tolerated, except for minor gastrointestinal symptoms at the beginning of the treatment and significantly improves motor symptoms compared with placebo in PD nonfluctuating patients.     

MRI of pancreatic gastrinomas.

Pancreatic islet cell tumors are often small and multiple, and preoperative diagnosis can be difficult. In a woman with hypergastrinemia, angiography and CT each depicted a solitary lesion. Magnetic resonance images, acquired using fat suppression, fast spin echo, and contrast material injection, depicted seven separate lesions, which were surgically confirmed.     

Preparation and pharmacologic activity of amido- derivatives of 3-methyl-3,4-dihydro benzo- and pyrido-1,2,4-triazin-3-acetic acids

Thirteen amidoderivatives of 3-methyl-3,4-dihydro-6-R-benzo-1,2,4-triazin-3-yl-acetic acids and of 3-methyl-3,4-dihydro-pyrido [3,2-e]/[3,4-e]-1,2,4-triazin- 3-yl-acetic acids were prepared and submitted to a wide pharmacological screening. The dihydrobenzotriazine and dihydropyridotriazine moieties were endowed with a wide pharmacogenic capacity; in fact, several compounds exhibited high antiinflammatory [(I c), (I d), (II d), (V f), (VI f)], diuretic [(I f), (I g), (I h)] and antihypertensive activities [(I d), (III d)], as well as minor effects on the C.N.S.     

The effects of THA on scopolamine and nucleus basalis lesion-induced EEG slowing

The effectiveness of THA (an anticholinesterae) on scopolamine (0.4 mg/kg) and nucleus basalis (NB) lesion-induced change in neocortical spectral electroencephalography (EEG) were investigated. Scopolamine increased the amplitudes of all the spectral components in waking-immobility. In the movement-related EEG spectral values, only the alpha power was increased. THA 7.5 mg/kg, but not THA 3 mg/kg, could reverse scopolamine-induced amplitude change. NB lesioning increased delta and theta amplitudes, but decreased beta amplitude. Delta amplitude was increased during movement recordings in NB-lesioned rats. THA 7.5 mg/kg and pilocarpine 10 mg/kg, but not THA 3 mg/kg, could partially reverse the increase of delta and theta amplitudes induced by NB lesions. However, the beta power decrease could not be restored with cholinomimetics. This study demonstrates that quantitative EEG activity analysis may reflect the THA-induced restoration of the function of the cholinergic nucleus basalis.     

Faecal lipids in familial adenomatosis coli

Faecal sterols and bile acids from six patients with familial adenomatosis coli (FPC) and 61 healthy men were analysed preoperatively. Faecal concentrations and secretion of neutral sterols, plant sterols, and degradation products of cholesterol were identical in the two groups. No increase was found in the faecal bile acid excretion, and the distribution of individual bile acids was normal in FPC. The results suggest that the development of adenomas in FPC is not associated with abnormal cholesterol and bile acid excretion.     

Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB).

PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder. INTRODUCTION: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein-binding domain (UBA) and representing a mutational hot spot area. MATERIALS AND METHODS: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases. RESULTS: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without. CONCLUSIONS: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder.