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Background: p53 and bcl-2 are two key genes involved in cell cycle and cell death regulation. Altered expression or mutation of these genes has been found in human cancers and also has been identified in clear cell renal carcinoma (RCC). Their role in RCC progression, however, is still unclear. By contrast, the prognostic significance of ploidy and S-phase fraction (SPF) have been studied extensively in RCC. To better characterize the biologic role of p53 and bcl-2 oncoproteins in RCC, we offer a multisample correlative analysis of the expression of these two proteins with ploidy and SPF., Methods: Ploidy and SPF along with p53 and bcl-2 expression were analyzed in 296 specimens, selected by multiple sampling of 33 consecutive operable RCCs. The expression of p53 and bcl-2 proteins was studied by immunohistochemistry, and SPF and tumor ploidy were studied by flow cytometry., Results: In our study, 4 of 32 (12.5%) were found to be diploid, and 28 of 32 (87.5%) cases showed an abnormal DNA content. Among the aneuploid tumors, 14 of 28 (50%) were multiploid. Heterogeneous DNA content was detected in 21 of 32 (65.6%) tumors and was correlated with the more advanced Robson stage tumor (P = 0. 03). Intratumor heterogeneity also was detected for p53 and bcl-2 protein expression. Expression of p53 protein correlated with the lack of bcl-2 protein expression (P = 0.0032), aneuploidy (P < 0. 0001), and high SPF (P = 0.0006), whereas bcl-2 expression was associated with a normal DNA content (P < 0.0001) and low SPF (P = 0. 035)., Conclusions: Within each RCC, p53 and bcl-2 expression is markedly heterogeneous. Our results depicted a scenario in which bcl-2 protein, expressed by normal renal parenchyma, is still present in euploid cell clones of RCC but disappears during the progression of renal neoplasm toward a more aggressive phenotype characterized by overexpression of p53 protein, aneuploidy, and high SPF.

Background: Helicobacter pylori, the main cause of chronic gastritis, is a class I gastric carcinogen. Chronic gastritis progresses to cancer through atrophy, metaplasia, and dysplasia. Precancerous phenotypic expression is generally associated with acquired genomic instability., Aim: To evaluate the effect of H pylori infection and its eradication on gastric histology, cell proliferation, DNA status, and oncogene expression., Methods/subjects: Morphometric and immunohistochemical techniques were used to examine gastric mucosal biopsy specimens from eight controls, 10 patients with H pylori negative chronic gastritis, 53 with H pylori positive chronic gastritis, and 11 with gastric cancer., Results: All patients with chronic gastritis were in a hyperproliferative state related to mucosal inflammation, regardless of H pylori infection. Atrophy was present in three of 10 patients with H pylori negative chronic gastritis and in 26 of 53 with H pylori positive chronic gastritis, associated in 18 with intestinal metaplasia. DNA content was abnormal in only 11 patients with atrophy and H pylori infection; eight of these also had c-Myc expression, associated in six cases with p53 expression. Fifty three patients with H pylori positive chronic gastritis were monitored for 12 months after antibiotic treatment: three dropped out; infection was eradicated in 45, in whom cell proliferation decreased in parallel with the reduction in gastritis activity; atrophy previously detected in 21/45 disappeared in five, regressed from moderate to mild in nine, and remained unchanged in seven; complete metaplasia disappeared in 4/14, and markers of genomic instability disappeared where previously present. In the five patients in whom H pylori persisted, atrophy, metaplasia, dysplasia, and markers of genomic instability remained unchanged., Conclusions: Chronic H pylori infection seems to be responsible for genomic instability in a subset of cases of H pylori positive chronic atrophic gastritis; eradication of H pylori infection can reverse inflammation and the related atrophy, metaplasia, and genomic instability.

Background: Serum alpha-L-fucosidase activity is considered a marker of hepatocellular carcinoma. To the authors' knowledge, its clinical usefulness in the early detection of hepatocellular carcinoma in the follow-up of cirrhotic patients has not been reported previously., Methods: The authors prospectively studied serum alpha-L-fucosidase activity, in addition to alpha-fetoprotein and ultrasonography, in a regular screening of 132 cirrhotic patients during an 8-year follow-up., Results: At enrollment, 120 patients had low alpha-L-fucosidase activity (below the cutoff value) and 12 had high activity. All patients had serum alpha-fetoprotein levels below the cutoff value. During the follow-up, hepatocellular carcinoma was detected in 19 patients, 16 with alpha-L-fucosidase activity below the cutoff value at enrollment and 3 with activity above it. In 7 of those 16 patients with carcinoma and low enzyme activity, the enzyme activity showed a significant increase 6-9 months before there was ultrasonographic evidence of a focal lesion, and by the time of diagnosis it had risen above the cutoff value in all of them; in only 3 of the 7 patients was the increase in alpha-L-fucosidase activity associated with an increase in alpha-fetoprotein. In another 4 of the 19 patients with carcinoma, only alpha-fetoprotein increased., Conclusions: Serum alpha-L-fucosidase activity is useful in the early detection of hepatocellular carcinoma. The data from this study suggest that cirrhotic patients who have a marked increase in serum alpha-L-fucosidase levels during follow-up should be closely monitored for signs of hepatocellular carcinoma development.

Objective: To define the value of silver-stained nucleolar organizer regions (AgNOR) in the evaluation of uveal malignant melanomas (MM)., Study Design: Morphometric analysis of AgNORs was performed on 30 uveal MM of spindle A, B, epithelioid and mixed cell types. Findings were compared with cytotype, largest tumor dimension (LTD) and clinical outcome., Results: AgNOR mean perimeter (MP) was 3.76 microns (SD 1.21, range 1.79-8.51 microns) in A, 5.05 microns (SD 1.96, range 1.79-16.41 microns) in B and 6.15 microns (SD 3.86, range 1.79-33.80 microns) in epithelioid MM; mean area (MA) was 0.86 micron 2 (SD 0.60, range 0.20-2.78 microns 2) in A, 1.58 microns 2 (SD 1.11, range 0.20-9.63 microns 2) in B and 2.34 microns 2 (SD 2.10, range 0.20-15.27 microns 2) in epithelioid MM; the aspect ratio (AR) was 3.10 (SD 0.19, range 2.90-3.35) in A, 5.80 (SD 2.07, range 3.77-9.32) in B and 12.22 (SD 2.84, range 8.11-15.81) in epithelioid MM. From comparing MA and RA with follow-up, it seemed that MM with a good prognosis (spindle A and a subgroup of B tumors, B1) exhibited the lowest MA and AR values, while MM with poorer clinical behavior (epithelioid and a second subgroup of spindle B MM, B2) showed the highest. No correlation was found between AgNORs and LTD., Conclusion: AgNORs may contribute to the prognostic evaluation of uveal MM.

In order to evaluate the effects of cilazapril on left structure and function in essential hypertension, we evaluated 10 patients (4 females and 6 males) affected with mild-to-moderate systemic hypertension. All patients were treated with cilazapril 5 mg/day over a 6-months period and underwent a 24 hours ambulatory blood pressure monitoring and a complete Doppler echocardiographic examination at study entry, after 3 and 6-months of therapy. After therapy, mean systolic and diastolic arterial pressure decreased significantly from 153 +/- 16/102 +/- 8 mmHg to 135 +/- 13/83 +/- 6 mmHg respectively (p < 0.005/0.001 respectively). Moreover there was a significant decrease of left ventricular mass from 109 +/- 27 to 87 +/- 23 g/m2 (p < 0.005). Ejection phase indices did not change significantly, whereas left ventricular diastolic filling improved after therapy with a significant increase of M1/M2 ratio from 0.9 +/- 0.2 to 1.1 +/- 0.3 (p < 0.02). In conclusion, these data demonstrate that cilazapril 5 mg/day is effective in reducing blood pressure in mild-to-moderate essential hypertension. This normalization of blood pressure measurements is paralleled by a significant decrease of left ventricular mass index and by an improvement of left ventricular diastolic filling.

A two years follow up on 105 diabetic patients and 50 normal subjects was carried out by high resolution real time echotomography, aiming to evaluate the prevalence and the evolutionary trends of carotid atherosclerotic plaques. The prevalence of atherosclerotic lesions was higher in diabetic patients than in normal subjects, and the most part of them showed an "intermediate" echographic pattern, minimal stenosis and regular surface. The results of the two years follow up indicate that the "soft" and the "hard" plaque types were those showing a more significant progression toward to the "mixed" type. "Hard" and "mixed" plaques, particularly those showing irregular surface, resulted most associated with higher degree of vessel stenosis. Four diabetic patients experienced three minor and one major ischemic events during the follow up; however all the patients had shown plaques with "intermediate" pattern, regular surface, and no signs of vessel stenosis progression. Further studies, performed for longer period of time with a higher number of patients are needed to evaluate the evolutionary trends of carotid plaques in diabetic patients and their relationship with clinical ischemic events.

The antihypertensive effect of a recently introduced antiserotoninic drug, ketanserin, was examined in a single-blind, placebo-controlled parallel group study in 28 patients with mild to moderate hypertension. Supine and standing blood pressure, electrocardiogram, heart rate and laboratory parameters of liver, kidney and bone marrow functions were checked before and after 3 months of treatment. After 12 weeks' treatment with ketanserin (20-40 mg twice a day), there was a highly significant reduction of both systolic and diastolic blood pressure, as compared to placebo in the supine position (p less than 0.0001/p less than 0.001). In the standing position, the reduction of systolic pressure was more significant than the diastolic pressure (p less than 0.0001/p less than 0.01). Eleven out of 28 hypertensive patients showed electrocardiographic evidence of left ventricular hypertrophy (LVH) according to the ECG criteria of Romhilt and Estes. Although a reduction of the mean point score for LVH as compared to placebo was observed in the ketanserin group, that difference was not statistically significant. These preliminary observations suggest a possible role of ketanserin in the regression of LVH due to essential hypertension.

A patient with Marfan syndrome and Schoenlein-Henoch purpura is reported. The diagnosis has been possible only by clinical criteria because no laboratory test is available to support the clinical impressions. Possible initial diagnostic confusion with other purpuric disorders is discussed.

An epidemiological study has been carried out on a group of 622 students (10 to 13 years old) from a secondary school in Naples. Aims of the present work were: the evaluation of the prevalence of hypertension in an adolescent population; the association with familial hypertension and obesity; the persistence of high blood pressure values at follow-up. Blood pressure data obtained in these subjects by the use of a standard evaluation scale based on body surface percentiles were compared with those obtained by two major current methods used for the definition of "normal" blood pressure values in pediatric age. The method based on body surface percentiles has shown the highest specificity. The prevalence of hypertension, as detected by this method, has been of 3,5% as compared to 12,9% and to 9,5% of the other two methods. In a follow-up at one year, while the percentage of hypertensive students remained unchanged in the group detected by the method of body surface percentiles, it decreased from 12,9% to 9,3% and from 9,5% to 7,8% in the other two groups. The high prevalence of obesity and familial hypertension observed in these young hypertensive subjects suggest the possibility of selecting, by body surface percentiles, well defined group of subjects at risk, characterized by borderline hypertension, high grade of familial aggregation, high prevalence of obesity and by the persistence of hypertension at the follow-up.