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Biomedical subjects

A Leone

Publications and source records attributed to A Leone.

At least 73 records · Page 4Linked to original sources

Anti-CEA immunoscintigraphy and computed tomographic scanning in the preoperative evaluation of mediastinal lymph nodes in lung cancer.

BACKGROUND: Thoracic computed tomography (CT) provides most of the staging information needed before operation for lung cancer and can reduce the number of exploratory thoracotomies. In recent years a new immunoscintigraphic technique with anti-carcinoembryonic antigen (CEA) monoclonal antibodies has been shown to be effective in lung cancer staging. This study compares the yields of CT scans and immunoscintigraphy in the preoperative evaluation of the medistinal lymph nodes of patients with non-small cell lung cancer. METHODS: One hundred and thirty one patients believed on clinical grounds to have a operable non-small cell lung cancer were photoscanned with the indium-111 labelled F(ab')2 fragments of the antibody FO23C5. Both planar and single photoemission computed tomography (SPECT) thoracic views were recorded. CT scan of the thorax, abdomen, and brain were obtained in all patients. Seventy of the patients eventually underwent surgery, an additional seven underwent mediastinoscopy or mediastinotomy, and a further 10 had both cervical exploration and thoracotomy. Pathological evaluation of the mediastinal nodes was available in all 87 patients, but in only 80 of them was the diagnosis of lung cancer eventually confirmed. RESULTS: The diagnostic accuracy of planar immunoscintigraphy, SPECT immunoscintigraphy, and CT scanning for N2 disease was 76%, 74%, and 71%, respectively. The corresponding sensitivity and specificity rates were 45%, 77%, 64% and 88%, 72%, and 74%. These were not significantly different. CONCLUSIONS: This study shows that anti-CEA immunoscintigraphy has no advantage over conventional CT scanning in assessing mediastinal lymphoadenopathy in patients with lung cancer. CT scanning remains the gold standard test in these patients.

Antibodies, Monoclonal↗

nm23 in ovarian cancer: correlation with clinical outcome and other clinicopathologic and biochemical prognostic parameters.

PURPOSE: The aim of the study was to define the prognostic role of the metastasis suppressor gene, nm23, in 106 primary ovarian cancer patients. PATIENTS AND METHODS: Northern and Western blotting analysis of nm23-H1 and nm23-H2 expression were performed in a subset of ovarian tumors. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens from 106 primary ovarian carcinomas by the antihuman nm23 monoclonal antibody. RESULTS: Northern and Western blotting analysis demonstrated a direct association between nm23-H1 and nm23-H2 levels. Moreover, an overall concordance of 86.7% between Northern blotting and immunohistochemical data was observed. Sixty-six specimens (68%) showed a positive nm23-H1 immunoreaction. The percentage of nm23-H1 positivity was higher in lymph node-negative (70%) than in lymph node-positive cases (44%) (P = .049). Moreover, the percentage of complete/partial responses to chemotherapy was higher in nm23-H1-positive (69%) than in nm23-H1-negative (44%) patients (P = .03). The percentage of epidermal growth factor receptor (EGFR) positive cases was lower in nm23-H1-positive (44%) than in nm23-H1-negative immunostained (72%) samples (P = .012). Lower ras/p21 levels (median, 1.77 absorbance units) were found in nm23-H1-positive than in nm23-H1-negative samples (median, 2.63 absorbance units) (P = .03). The 6-year progression-free survival (PFS) rate of nm23-H1-positive cases was 50% (95% confidence interval [CI], 33 to 67) versus 12% (95% CI, -2 to 26) for nm23-H1-negative patients (P = .0056). In multivariate analysis, only stage, ascites, and nm23-H1 content retained independent prognostic roles. CONCLUSION: The assessment of nm23 content may provide useful information for prognostic characterization of ovarian cancer patients.

Blotting, Northern↗

Causes of death from myocardial infarction before and after thrombolysis era: a pathologic study.

One hundred and sixty-eight out of 296 patients who died of acute myocardial infarction (AMI) in the Coronary Care Unit were studied to assess the cause of death. Twenty-two of them had received thrombolytic therapy. The mean age of these patients was 64.3 +/- 18.2 years. One hundred and eight subjects were male and 60 were female. One hundred and nine cases (64.8%) showed, at postmortem examination, histopathologic alterations due to acute myocardial infarction (AMI). Death was due to heart failure in 35.8%, cardiogenic shock in 20% and ventricular arrhythmia in 44%. The other 59 patients died from complications superimposed upon AMI: reinfarction (23.7%), heart rupture (40.7%), myocardial fibrosis and reinfarction (18.6%), and cerebral infarction (17%). Two of these patients also showed massive pneumonia. In those subjects who had received thrombolytic therapy, a broad spectrum of arrhythmic and haemorrhagic complications were seen (68%). Four causes of death were seen in the subjects studied: AMI, superimposed cardiac complications, side-effects of thrombolytic treatment, and non-cardiac causes. Patients who did not receive thrombolysis mechanical events eg heart failure, characterized their deaths. In subjects who had received thrombolytic therapy, arrhythmic and haemorrhagic were widely observed.

Adult↗

[Role of computerized tomography in percutaneous drainage of acute infected necrotic-hemorrhagic pancreatitis].

In the last few years, Computed Tomography (CT) has emerged as the most sensitive and reliable imaging technique to diagnose acute pancreatitis (AP). Besides assessing the extent of damage to the pancreas and to periglandular tissue. CT can recognize the major early and late complications of the disease promptly and with extreme accuracy. We investigated the diagnostic capabilities of CT in controlling AP development and tried to assess the role of interventional radiology as a therapeutic support after or instead of surgery in treating the necrotic forms of pancreatitis complicated by sepsis. From 1989 to 1995, acute pancreatitis mostly due to biliary tract disease and alcoholism was diagnosed in 228 patients. Necrotic processes were identified in 105 of them since disease onset; septic complications developed in 57 patients. Surgery was performed in 42 patients, but the result was poor in 11 of them (30%) and CT showed the persistence of some infectious pancreatic exudate which had been drained insufficiently. Since sepsis persisted in these patients, the exudate was aspirated percutaneously after positioning appropriate drainage means guided by abdominal CT. Sepsis resolved completely in 10 patients, while one required subsequent surgery. Percutaneous drainage catheters were positioned in 15 patients as the treatment of choice, under CT and US guidance. Sepsis resolved in 7 cases only (45%), while 3 of the extant patients died and 5 needed surgery. The results of our experience demonstrate the effectiveness of percutaneous drainage under CT guidance. However, this technique should be used after and as a support to surgery, the latter remaining the treatment of choice for infectious necrotic AP. Thus, in our experience, the use of percutaneous aspiration instead of surgery proved to be a less effective tool in curing this condition and its use should therefore be limited to high-risk surgical patients.

Acute Disease↗

Congenital toxoplasmosis: 10-year follow up.

A long-term follow up was begun in 1982 on offspring of mothers who acquired toxoplasmosis during gestation. The 114 newborns were subdivided into 3 groups: (1) 26 born to mothers with certain infection; (2) 51 born to mothers with probable infection, and (3) 37 born to mothers with doubtful infection. There were five infections in the first group (19.2%), three in the second (5.8%) and none in the third. For purposes of data elaboration we considered only the 77 offspring of mothers with certain or probable infection. Of these, 2 infected cases out of 52 (3.8%) were born to mothers with infection in the first trimester of pregnancy, 4 out of 21 (19%) in the second trimester, and two out of four in the third. There were a total of 8 congenital infections (10.4%). Specific IgM antibodies were revealed in five out of eight infected children (62.5%). Infection was symptomatic in two children (2.6% of newborns at risk, 25% of infected cases), both born to mothers with infection in the second trimester. In the other six cases diagnosis was reached by evaluating trends in antibody levels: the percentage of infected newborns was higher in the group of maternal infections untreated (50%) or improperly treated (15.4%), compared to those receiving adequate treatment (6.9%). We suggest considering as infected children presenting specific IgM antibodies and/or antibody titres which do not become negative, even when symptoms are absent. Therapy with spiramycin should be started in all newborns at risk, while the use of sulphamides and pyrimethamine is justified only after the presence of infection is confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Protozoan↗

Transcutaneous PCO2 level as an index of tissue resistance to ischemia.

The authors performed a retrospective study on a data base of 525 patients with peripheral arterial disease, to analyze the pathophysiologic meaning of resting transcutaneous pressure of carbon dioxide (PCO2) and of CO2 production during three minutes of local ischemia. The resting and postischemic PCO2 and its maximum increase related to rest (PCO2 production) were measured with Kontron 7640 equipment. The results show a significant increase of PCO2 production in the Fontaine stage 2A (183 patients, 4.61 mmHg, P < 0.0001), in stage 2B (194 patients, 5.22 mmHg, P < 0.0001), in the third stage (83 patients, 6.10 mmHg, P < 0.0001), and in the fourth stage (53 patients, 8.66 mmHg, P < 0.0001). Only the patients at the first stage showed an insignificant increase, perhaps because of the small number (12) in this group. The authors feel that the measurement of tcPCO2 production during local ischemic stress can be a very important parameter for evaluating peripheral arterial disease as an expression of metabolic tissue performance and, overall, of the tissue resistance to ischemia.

Arterial Occlusive Diseases↗

Cigarette smoking and health of the heart.

A large series of studies relate cigarette smoking to the development of cardiovascular damage. Both active and passive smoking seem to act negatively on the heart, although with different results. Active smoking impairs the cardiovascular system chronically causing mainly coronary atherosclerosis, whereas passive smoking impairs cardiac performance transiently after acute exposure, and to a greater extent in those with established ischaemic heart disease. Evidence indicates that the heart is a target organ for cigarette smoking (Leone, 1992). Diseases of the heart and blood vessels account for over one-third of all the excess deaths in smokers (follow-up report of the Royal College of Physicians, 1983). The purpose of this report is to demonstrate some of the links between cardiovascular damage and smoking by reviewing our previous findings based on an Italian population.

Adult↗

Prognostic significance of the loss of heterozygosity of Nm23-H1 and p53 genes in human colorectal carcinomas.

BACKGROUND: Nm23 is a gene associated with low tumor metastatic potential and has been proposed to be a metastasis suppressor gene. Nm23 is localized on chromosome 17q21.3-22, whereas the p53 suppressor gene is on 17p13. Allelic deletions of chromosome 17 have been related to the progression of colorectal carcinomas. The purpose of this study was to analyze the allelic deletions of Nm23 and p53 in colorectal carcinomas and to assess their prognostic significance in the evolution of the patients. METHODS: Allelic deletions of Nm23 and p53 genes were studied in 56 colorectal carcinomas using different restriction fragment length polymorphisms. DNA ploidy and proliferative activity of the tumors were studied by flow cytometry. Actuarial disease free and overall survival were analyzed by the Kaplan--Meier method, and the curves were compared with the log rank test. RESULTS: Thirty-eight patients were heterozygous for Nm23 gene (68%), and 9 of them (24%) exhibited a loss of heterozygosity in the tumor sample. One of the homozygous patients showed a loss of both Nm23 alleles. Allelic deletions of 17p13 were found in 63% of the 41 informative patients. All patients' tumors that had loss of heterozygosity of the Nm23-H1 locus also had allelic losses on the short arm of chromosome 17 (17p13) and in other loci on 17q. No relationship was found between localization, invasion, lymph node metastasis, or proliferative index of the tumors and the allelic deletions of the Nm23-H1 or 17p13 locus. Nm23-H1 deletions were relatively more frequent in poorly differentiated adenocarcinomas (P = 0.03). A significant association between 17p13 deletions and DNA aneuploidy was found (P = 0.016). A similar tendency was observed with Nm23-H1 deletions (P = 0.051). Loss of Nm23-H1, but not of 17p13, was significantly associated with a shorter disease free (P = 0.025) and overall (P = 0.04) patient survival. CONCLUSIONS: Allelic deletions of Nm23-H1 are significantly associated with a more aggressive behavior of colorectal carcinomas. The loss of this gene seems to be part of extensive deletions of chromosome 17, and it is also associated with DNA aneuploidy. More studies are needed to determine whether Nm23-H1 or a gene linked to this locus is the specific target of the progression of these tumors.

Adenocarcinoma↗

Interactions of nuclear proteins from uninduced, induced and superinduced HeLa cells with metal regulatory elements MRE3 and 4 of the human metallothionein IIa-encoding gene.

Transcriptional activation of metallothionein (MT)-encoding genes(MT) is regulated during heavy metal induction by short non-identical repeats, termed 'metal regulatory elements' (MRE), present in multiple imperfect copies in MT promoter regions of eukaryotes. Using mobility shift assays, we have studied the interaction between the human MRE 3 and 4 regions (hMRE3/4) of the MTIIa promoter and nuclear proteins from uninduced and Cd(2+)-induced HeLa cells, and from Cd(2+)-superinduced H454 cells, a HeLa-derived Cd(2+)-resistant cell isolate which overexpresses hMTIIa after exposure to metal. A specific complex with a similar electrophoretic mobility was formed in all three extracts. Dialysis of the extracts using EDTA inhibited the formation of the complexes, which could be reconstituted only after the addition of Zn2+. UV cross-linking analyses of the specific complexes formed by the three nuclear extracts interacting with the hMRE3/4 region revealed that in all of them polypeptides were present having similar electrophoretic mobilities and different molecular masses. Mobility shift assays showed no major differences in the binding of nuclear proteins from induced or uninduced cells. Proposed models of activation of metal-induced MT transcription are discussed.

Base Sequence↗

Effects of a nitric oxide synthase inhibitor in humans with septic shock.

OBJECTIVE: Studies in animals have indicated that increased production of nitric oxide from an inducible isoform of nitric oxide synthase contributes to the pathophysiology of endotoxic and cytokine induced shock. The aim of this study was to determine the role of nitric oxide in septic shock in humans. METHODS: The study was a randomised, double blind, placebo controlled investigation of the effects of the nitric oxide synthase inhibitor NG monomethyl-L-arginine (L-NMMA) in 12 patients with severe sepsis associated with hypotension. Measurements of haemodynamic, haematological, and biochemical variables were made. RESULTS: L-NMMA (0.3 and 1 mg.kg-1) produced a dose dependent increase in mean arterial pressure, systemic vascular resistance, pulmonary vascular resistance, central venous pressure, and pulmonary artery occlusion pressure, and a decrease in cardiac output and heart rate. In response to the highest dose of L-NMMA systemic vascular resistance increased from 547(SEM 92) to 889(143) dyne.s.cm-5, mean arterial blood pressure increased from 80.9(2.9) to 100.5(6.1) mm Hg, and cardiac output decreased from 11.2(2.1) to 8.9(1.9) litres.min-1. Continuous infusion of L-NMMA (1 mg.kg-1 x h-1) produced sustained haemodynamic changes. Platelet numbers decreased during the course of the study in both the L-NMMA and the placebo group and did not differ significantly between the groups. CONCLUSIONS: Low doses of L-NMMA cause a widespread increase in vascular tone and raise blood pressure in patients with septic shock. Overproduction of nitric oxide appears to be an important mechanism in septic shock in patients, and inhibition of nitric oxide synthesis might provide a novel therapeutic approach to this condition. However, L-NMMA produced a fall in cardiac output and it is possible that this would worsen tissue perfusion. Larger studies examining the effects of L-NMMA on mortality and morbidity are now required.

Adult↗

Efficacy of 2'-deoxy-2'-fluororibosides against influenza A and B viruses in ferrets.

Single-dose treatments (5 to 40 mg/kg of body weight given intraperitoneally) of ferrets with 2'-deoxy-2'-fluoroguanosine or its prodrug, 2,6-diamino-purine-2'-fluororiboside, 1 h after infection with influenza A virus significantly inhibited replication of virus in the upper respiratory tract, resulting in amelioration of fever and nasal inflammation. Replication of virus in the lower respiratory tract was also reduced > 100-fold, but three doses were required to prevent replication in the lungs. In ferrets infected with influenza B virus, single-dose treatment (40 mg/kg given intraperitoneally) produced a similar but reduced response in comparison with that in ferrets infected with influenza A virus, indicating that dosing was not optimal for this virus.

Adenosine↗

Cigarette smoking and cardiovascular damage: analytic review of the subject.

A large series of epidemiological, clinical and pathological studies relate cigarette smoking to the development of cardiac damage. Data of our studies on both active and passive smoking show the following results. (A) Active smoking: (i) clinical and electrocardiographic signs of myocardial ischaemia were seen in 266 (38%) out of 700 smokers vs 25 (12.5%) out of 200 non-smokers (p < 0.01) with similar characteristics, (ii) a significantly higher incidence (p < 0.05) of reinfarctions in 443 smokers who continued to smoke (200 reinfarctions, 45%) compared to 724 subjects with a previous infarction who stopped smoking (289 reinfarctions, 40%), (iii) a significantly higher incidence of reinfarction in smokers with a previous myocardial infarction who smoked more than 15 cigarettes per day compared to a similar population who smoked less than 15 cigarettes per day (118/212, 56% vs 82/231, 35%). (B) Passive smoking: 19 male volunteers (9 healthy and 10 with a previous myocardial infarction), who did not smoke, underwent exercise stress testing twice; once in a smoke-free environment and once in a smoking environment. Cardiac performance of these subjects was impaired significantly in the smoking environment. Pathologically, severe coronary alterations, especially in users of oral contraceptives, massive myocardial infarctions and focal myocardial lesions were seen. Several variables such as type of smoking, subject and environment may interfere with experimental results. When we standardise these variables, cardiac damage caused by cigarette smoking is an undoubted fact.

Adult↗

[The role of computed tomography and magnetic resonance in assessing degenerative arthropathy of the lumbar articular facets].

Degenerative arthropathy of the lumbar facet joints remains a debated issue relative to both its etiopathogenesis and its clinical significance. The authors studied 9 autoptic specimens by means of CT and MRI: the diagnostic value of the two methods was assessed taking the histopathologic findings of the relative specimens as the gold standard. The following signs of degenerative arthropathy were investigated in each specimen: cartilaginous wears, hypertrophy of the articular processes, osteophytosis, subchondral sclerosis and geodes and capsular and ligamentous calcifications. CT clearly demonstrated the characteristic signs of arthropathy, although failing to assess the cartilaginous wears in the early degeneration phases. Cartilaginous surface tears were directly depicted by MRI in the specimens showing medium and advanced degeneration. In our opinion, CT represents the examination of choice in the diagnosis of degenerative arthropathy of the lumbar apophyseal joints. Nevertheless, human trials are needed to assess MR capabilities in better detailing subchondral bone structure and in depicting the joint capsule and the synovial membrane and fluid as a major MR potential to diagnose back pain syndromes arising from the posterior arch.

Aged↗

Non-fistulous idiopathic coronary artery aneurysm. Report of three cases and literature review.

Non-fistulous idiopathic aneurysm of coronary arteries is a rare anomaly, often localized on the left coronary trunk and diagnosed in young patients following myocardial ischemia. Diagnosis before death is only possible since advent of selective coronary angiography. Idiopathic etiology can be inferred when the aneurysm is found in the absence of atherosclerosis and calcification of other arteries and if there is an absence of risk factors for atherosclerosis. Inflammatory etiology is excluded by a negative clinical history and lack of histologic inflammatory features. However, cumulating observations suggest that angeitis or other acquired process cannot definitely be disapproved. Advances in coronary artery surgery have permitted resection of aneurysms and grafting of involved coronary artery since the early seventies. Three cases of non-fistulous idiopathic aneurysms of coronary arteries are presented. The literature has been reviewed and the clinical, anatomic, angiographic findings and management are discussed.

Adult↗

Preliminary molecular analysis of a case of feline mucopolysaccharidosis VI.

Deficiency of the lysosomal enzyme arylsulphatase B (ASB) causes, in man, the Maroteaux-Lamy disease (mucopolysaccharidosis type VI, MPS VI). MPS VI has been described also in Siamese cats. Isolation and characterization of the human and feline cDNAs encoding ASB has been reported as well as the assignment of the feline ASB gene to feline chromosome A1. The present paper describes the Southern and Northern blot analyses on DNA and RNA from an MPS VI affected cat using the human arylsulphatase B probe (ASB2). Our data suggest that a gross deletion/rearrangement of the ASB gene is present in the affected animal.

Animals↗

Nm23 and breast cancer metastasis.

The majority of breast cancer patients succumb to metastatic disease. We summarize published and recent research concerning the nm23 gene in breast cancer metastasis. In a murine developmental study, nm23 expression increased with the functional differentiation of the mammary gland in nulliparous and pregnant animals. In human breast cancer, five studies have now demonstrated a significant association between reduced nm23 expression, at the RNA or protein levels, and aggressive tumor behavior. Nm23-negative tumor cells have been observed in comedo ductal carcinoma in situ lesions in two independent studies, indicating that decreases in nm23 expression begin prior to actual histologically identifiable invasion. Transfection studies, in which human nm23-H1 cDNA was expressed in the metastatic human MDA-MB-435 breast carcinoma cell line, indicate that nm23-H1 suppresses in vivo metastatic potential by 50-90%. Finally, our data in melanoma and breast carcinoma transfection systems suggest that the biochemical mechanism of nm23 suppressive activity is likely not due to its nucleoside diphosphate kinase activity, association with GAP proteins, or secretion from cells.

Animals↗