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Biomedical subjects

G Ranieri

Publications and source records attributed to G Ranieri.

At least 19 recordsLinked to original sources
PubMed1998

Prognostic significance of p53, angiogenesis, and other conventional features in operable breast cancer: subanalysis in node-positive and node-negative patients.

To validate the prognostic value of the determination of p53 expression, intratumoral microvessel density (IMD) (a measure of angiogenesis), and the conventional features, we studied 531 patients operated of breast cancer (271 node-positive and 260 node-negative), with a median follow-up exceeding 6 years. IMD was assessed by using the anti-CD31 antibody to identify the microvessels. p53, estrogen receptor (ER) and progesterone receptor (PgR) were determined by immunocytochemistry using the antibodies PAb1801, H-222 Sp2y and KD-68, respectively. The prognostic value of the markers was analyzed by univariate and multivariate statistical analyses. In the overall series p53 expression, IMD, nodal status, ER and PgR were statistically significant prognostic indicators for both relapse-free survival (RFS) and overall survival (OS) in the final multivariate model. Likewise, tumor size and menopausal status were significant prognostic indicators for RFS and OS, respectively. In the subgroup of node-negative patients who did not receive adjuvant therapy only p53, IMD, and tumor size were statistically significant in multivariate analysis. In the subgroup of node-positive patients treated with adjuvant chemotherapy, IMD, the number of involved nodes and PgR were statistically significant in multivariate analysis. In the subgroup of node-positive patients treated with adjuvant tamoxifen, IMD and ER (and the number of involved nodes, only for OS) were statistically significant for both RFS and OS in the final multivariate model. Different markers played a diverse prognostic role in the diverse subgroups studied. Angiogenesis was the sole marker which retained prognostic value in all the sub-groups analyzed. p53 retained significance only in the subgroup of node-negative patients, whilst ER and PgR were statistically significant in the subgroups of node-positive patients treated with adjuvant hormone therapy or chemotherapy, respectively.

Adult↗
PubMed1998

Vascular integrin alpha(v)beta3: a new prognostic indicator in breast cancer.

Blood vessel density is a prognostic indicator of multiple tumor types. Recently, it has been established that tumor-associated blood vessels express elevated levels of integrin alpha(v)beta3. In fact, there is evidence that integrin alpha(v)beta3 identifies the most proliferative endothelial cells within human breast carcinomas. Therefore, we evaluated breast cancer tissue in terms of both blood vessel density and alpha(v)beta3 expression. We found that the antibody LM609 to integrin alpha(v)beta3 preferentially stains the blood vessels of small caliber. Furthermore, comparative studies between LM609 and anti-CD31 antibodies on normal breast indicate that very low and weak expression of integrin alpha(v)beta3 was found on vessels within normal tissue, whereas CD31 antigen was expressed in almost all vasculature. Indeed, expression of integrin alpha(v)beta3 was significantly higher in tumors of patients with metastasis than in those without metastasis. In a series of 197 consecutive patients with invasive breast cancer and long follow-up, vascular expression of integrin alpha(v)beta3 in tumor vascular "hot spots" was found to be the most significant prognostic factor predictive of relapse-free survival in both node-negative and node-positive patients. These findings support the contention that angiogenesis plays a critical role in breast cancer progression and suggest that integrin alpha(v)beta3 is an endothelial cell marker with significant prognostic value and potential usefulness as a target for specific antiangiogenic therapy.

Adult↗
PubMed1996

Effects of isradipine sustained release on platelet function and fibrinolysis in essential hypertensives with or without other risk factors.

The aim of this study was to assess the chronic effects of a highly selective dihydropiridine calcium channel blocker, israpidine, in its sustained release form (I-SRO), on platelet functions and fibrinolytic parameters in subjects with essential hypertension (EH) combined or not with other well-known cardiovascular risk factors, such as cigarette smoking (EH+S) and type II diabetes mellitus (EH+DM). Thirty-six patients with essential hypertension with sitting diastolic blood pressures of 96-104 mmHg without (EH, n = 12) or with other risk factors (EH+S, n = 12, EH+DM, n = 12) were enrolled. After a 4-week, single-blind, placebo run-in period, the subjects received I-SRO 5 mg once daily for 18 weeks. After both placebo and 6 and 18 weeks of I-SRO treatment, the following parameters were measured: sitting blood pressure by mercury sphygmomanometer; platelet aggregation, plasma beta-thromboglobulin (BTG), platelet factor-4 (PF4), and plasminogen activator inhibitor 1 (PAI-1) by means of ELISA methods; and euglobulin lysis time before (ELT) and after standardized (10 min) venous occlusion (ELT-VO). In the group of patients as a whole compared with placebo, I-SRO significantly reduced SBP/DBP platelet aggregation, BTG, PF4, ELT, and ELT-VO. Significant reductions in these parameters were also observed in each group. In addition to the antihypertensive effect, I-SRO chronic treatment may favorably affect the platelet function and fibrinolytic system in essential hypertension with or without other cardiovascular risk factors.

Antihypertensive Agents↗
PubMed1996

Effects of benazepril and nicardipine on microalbuminuria in normotensive and hypertensive patients with diabetes.

Diabetic nephropathy is the most frequent cause of chronic renal failure. The onset of microalbuminuria in patients with diabetes mellitus, which seems to be related to blood pressure and the control of glycemia, is predictive of the development of true proteinuria. This multicenter, single-blind, randomized study examined the effects of benazepril and nicardipine on overnight microalbuminuria in 57 normotensive and 46 hypertensive diabetic patients. At the end of a 3-month placebo run-in period, the patients were stratified on the basis of the presence or absence of arterial hypertension and, within each stratum, randomized to receive one daily tablet of 10 mg benazepril or one tablet of 20 mg nicardipine twice daily for 6 months. Renal hemodynamics was investigated in 25 patients. Both drugs decreased overnight microalbuminuria throughout the study period, but benazepril was more effective than nicardipine (p = 0.025); in the patients with hypertension, both drugs led to a similar marked reduction in systolic and diastolic blood pressure. This study shows that benazepril was more effective than nicardipine in reducing overnight microalbuminuria in patients with diabetes mellitus, independently of their antihypertensive properties.

Adult↗
PubMed1996

The chick embryo chorioallantoic membrane as an in vivo wound healing model.

The chick embryo chorioallantoic membrane (CAM) was used as an in vivo wound healing model. A full excision of a 1 mm2 CAM area was filled by a granulation tissue after 96-120 h, which eventually formed a scar in 75% of the cases. In the remaining 25%, a solution of continuity was left which, however, was smaller in size than the one observed immediately after the excision. Under the microscope, the CAM area involved in the repair process showed: i. hyperplasia of the chorionic epithelium; ii. about three times as many microvessels and fibroblasts in the mesenchyme as in the normal adjacent control regions; iii. an inflammatory infiltrate mostly consisting of macrophages; and iv. a strong positivity for fibronectin in the extracellular matrix. The validity of this experimental model appears to be confirmed by the fact that we were able to reproduce all the critical events controlling the wound healing process, such as re-epithelization, angiogenesis, formation of an inflammatory infiltrate and deposition of one of the main constituents of the extracellular matrix, such as fibronectin.

Allantois↗
PubMed1994

Effects of lisinopril and amlodipine on microalbuminuria and renal function in patients with hypertension.

Many patients with arterial hypertension have abnormal urinary excretion levels of albumin. This study was aimed at examining the effects of lisinopril and amlodipine on urinary excretion of albumin and kidney function. Thirty-six previously untreated patients with essential arterial hypertension were divided randomly into two groups. The first group received lisinopril 20 mg daily for 12 weeks followed by 10 mg amlodipine daily for another 12 weeks. The second group received 10 mg amlodipine daily for 12 weeks followed by 20 mg lisinopril daily for another 12 weeks. The arterial pressure decreased in a similar way with both therapies in both groups. In both groups urinary albumin excretion decreased in patients receiving lisinopril (p < 0.01). No significant changes were observed with amlodipine. This study shows that lisinopril, but not amlodipine, is able to reduce urinary excretion of albumin in patients with essential hypertension independently of its effective antihypertensive properties. It is probable that the positive effect of lisinopril on microalbuminuria is attributable to the modifications in intrarenal hemodynamics or to a change in glomerular permeability.

Adult↗
PubMed1994

Twenty-four-hour ambulatory blood pressure monitoring and antihypertensive treatment: focus on ACE inhibitors.

The use of ambulatory blood pressure monitoring in clinical studies offers some advantages in comparison to the clinic blood pressure measurement. In fact, this approach does not induce any alerting reaction and provides 24-h blood pressure values that are more reproducible and not affected by the placebo effect. This allows a better evaluation of blood pressure under antihypertensive treatment and an optimization of the number of patients to be studied in pharmacologic trials. In a recent double-blind, parallel-group study, ambulatory blood pressure monitoring was used to investigate the antihypertensive efficacy of a new angiotensin-converting enzyme inhibitor, trandolapril, in 62 mild and moderate hypertensive patients. After a washout period, patients received trandolapril, 2 mg o.d., or placebo for 6 weeks, followed by a second washout period. Clinic and 24-h blood pressures were assessed at the end of each period. In comparing the pre- and post-treatment period, trandolapril significantly reduced clinic and 24-h systolic and diastolic blood pressures. The fall was evident throughout the 24 h and was statistically significant also in the last 4 h of blood pressure monitoring. The placebo group did not show any significant blood pressure change. Thus, trandolapril, 2 mg once daily, is effective in reducing blood pressure. Its efficacy over 24 h is better documented by 24-h blood pressure monitoring than by isolated clinic blood pressure measurement.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Bone marrow angiogenesis and progression in multiple myeloma.

Tumour growth is angiogenesis-dependent. We found a high correlation between the extent of bone marrow angiogenesis, evaluated as microvessel area, and the proliferating (S-phase) fraction of marrow plasma cells, evaluated as labelling index (LI), in patients with multiple myeloma (MM) and in those with monoclonal gammopathies of undetermined significance (MGUS). Angiogenesis itself was significantly associated with active as opposed to non-active MM and MGUS. The highest microvessel area accompanied rapidly progressive MM with the highest LI. When a cut-off value of 2% or greater of the microvessel area was used, most patients with active MM were classified correctly. The risk of active disease in patients with MM increased in parallel with the microvessel area. A causal relationship between plasma cell growth, activity phase in MM and marrow angiogenesis is suggested. Since angiogenesis proceeds in step with the enlargement of plasma cell tumours and the activity phase in MM, its measurement could be a useful prognostic marker in patients with plasma cell proliferative disorders.

Aged↗
PubMed1994

Differential expression of two ICAM-1 epitopes and LFA-1 chains in B-cell non-Hodgkin's lymphomas.

B-cell non-Hodgkin's lymphomas (B-NHL) and B-cell areas of reactive lymphadenopathies were investigated immunohistochemically for expression of two distinct ICAM-1 epitopes, Me14/D12 and P3-58, and the LFA-1 alpha and beta chains. Partial or total loss of expression of one or both epitope(s) and/or chain(s) was evident in all B-NHL in function of increasing Working Formulation (WF) malignancy grade, with most defects in the high-grade tumors, namely the lowest detectability of the ICAM-1 Me14/D12 and LFA-1 alpha chain, the lowest co-expression of ICAM-1 epitopes and LFA-1 chains, and the most frequent simultaneous loss. The ICAM-1 and LFA-1 profiles overlapped within the low- and intermediate-grades, whereas striking differences between the high-grade subtypes were detected. Specifically, Burkitt's and lymphoblastic tumors always lost both epitopes and both chains. Large cell, immunoblastic tumors occasionally did so, and also showed either uncoordinated expression or co-expression of these constituents. It is suggested that expression defects of this type may help differentiate malignant from benign lymphoproliferations, and also be involved in the progression of B-NHL, since most are observed in high-grade tumors, whose ICAM-1 and LFA-1 profiles indicate that their subtypes are the expression of distinct normal B-cell differentiation stages.

Antibodies, Monoclonal↗
PubMed1993

Forearm arterial distensibility in patients with hypertension: comparative effects of long-term ACE inhibition and beta-blocking.

Fifty patients with mild or moderate hypertension were assessed for the influence on peripheral hemodynamics of 10 months of treatment with lisinopril (25 patients) or metoprolol (25 patients). Two-dimensional Doppler flowmetry was used for the evaluation. Responding patients (blood pressure < 150/90 mm Hg) were monitored for another 4 weeks after treatment withdrawal to determine whether changes in forearm hemodynamics, if any, persisted. Twenty-two patients from either group (88%) were considered to be responders. Systolic and diastolic blood pressure in patients receiving lisinopril dropped by 6% and 15%, respectively (p < 0.001), in those receiving metoprolol the decrease was 5.9% and 14%, respectively (p < 0.001). Forearm hemodynamics was not significantly different before treatment and improved in patients receiving lisinopril, with increased compliance (p < 0.001) and lower vascular resistance (p < 0.001). No significant changes were observed with metoprolol. After withdrawal, blood pressure returned to baseline values in both groups. However, improvement in forearm hemodynamics persisted in the lisinopril group. Hemodynamics changes were statistically different on lisinopril versus metoprolol both after treatment and after withdrawal. Lisinopril, but not metoprolol, seems capable to induce regression of functional and/or structural changes of large arteries in patients with hypertension.

Adult↗
PubMed1993

Effects of atenolol and enalapril on kidney function in hypertensive diabetic patients.

The aim of the study was to evaluate the efficacy of enalapril and atenolol in decreasing the severity of proteinuria in hypertensive patients suffering from insulin-dependent diabetes mellitus. We studied 20 hypertensive patients. All patients had proteinuria (> 3 g/24 h) and were receiving insulin treatment. Proteinuria was measured monthly in the run-in period (3 months) and during the active drug treatment (8 months). Glomerular filtration rate, effective renal plasma flow, filtration fraction, and total renal resistance were determined after the run-in and treatment periods. The patients were randomly assigned to treatment with enalapril 20 mg/day or atenolol 100 mg/day for 8 months. In both groups blood pressure decreased significantly. After 8 months' treatment, severity of proteinuria significantly decreased both in the enalapril-treated group and in the group receiving atenolol. Glomerular filtration rate and effective renal plasma flow significantly increased, while total renal resistance decreased in the patients given enalapril, whereas glomerular filtration rate, renal plasma flow, and total renal resistance significantly decreased in the patients given atenolol. The results of this study show that enalapril and atenolol reduce proteinuria in hypertensive diabetic patients by a mechanism related to their antihypertensive effects; furthermore, the beneficial effects of enalapril might be also linked to intrarenal effects.

Adult↗
PubMed1993

Glucose and lipid metabolism in essential hypertension: effects of diuretics and ACE-inhibitors.

Various aspects of carbohydrate and lipid metabolism were studied in two groups of patients with mild hypertension before and after 6 months' treatment with either lisinopril (n = 10) or hydrochlorothiazide (n = 10). A significant reduction of arterial blood pressure was seen after both treatment regimens. Circulating plasma glucose, insulin, C-peptide and triglyceride concentrations were measured at hourly intervals from 8.00 a.m. to 5.00 p.m. in patients on an isocaloric diet (35 cal/kg/day). Plasma glucose concentrations remained unchanged, while insulin and C-peptide concentrations were higher in association with hydrochlorothiazide treatment. Conversely, lisinopril-treated patients had lower C-peptide concentrations after treatment. The changes in daylong plasma glucose and insulin-stimulated glucose uptake increased after hydrochlorothiazide treatment and decreased following lisinopril. Lastly, plasma cholesterol concentrations did not change after lisinopril therapy, whereas plasma high density cholesterol decreased as a result of hydrochlorothiazide treatment.

Blood Glucose↗
PubMed1993

[Antihypertensive action of nicardipine retard in 24 hours and its effect on stress].

Thirty-six patients (17 males and 19 females), aged between 40 and 70 years old (mean age 55.9), suffering from slight or moderate arterial hypertension, were monitored for four weeks after 14 days of placebo treatment. In a double-blind and random study 24 patients were treated with Nicardipine Retard (40 mg twice a day) whereas a further 12 received placebo twice a day. Sphigomanometric controls carried out after two and four weeks showed a significant reduction in arterial pressure only in those patients receiving active treatment. 24-hour out-patient monitoring of arterial pressure, carried out using Spacelabs 5300, showed a reduction in both systolic and diastolic arterial pressure throughout the day in subjects treated with calcium-antagonists compared to the placebo group. The normal physiological 24-hour trend of arterial pressure was always taken into account. The pressure response to a cold pressor test, mental arithmetic test, isometric and dynamic effort tests, measuring using a cycloergometer, was not modified by anti-hypertensive treatment, thus confirming the preservation of normal physiological behaviour during daily activities. There was no significant change in heart rate and the drug was well tolerated.

Adult↗
PubMed1993

[Slow-release nicardipine in the treatment of arterial hypertension: comparative study vs. an ACE inhibitor].

The anti-hypertensive activity and influence on some forms of stress of slow-release Nicardipoine and Captopril were compared using a randomized 2:1 protocol. Thirty-six patients, mean age 55.9 years, suffering from slight or moderate arterial hypertension were treated with either 40 mg of Nicardipine retard twice a day (b.i.d.), or Captopril in a dose of 25 mg (b.i.d.) for 8 weeks. A significant reduction was observed in arterial pressure, both in orthostatism and clinostatism, following both treatments in comparison to the placebo period, but the group treated with slow-release Nicardipine showed a greater and statistically significant reduction in arterial pressure. No significant change in heart rate was reported using either drug. Non-invasive out-patient monitoring of arterial pressure, performed using Spacelabs 5300, showed a significant reduction in arterial pressure using both drugs and the conservation of the normal circadian rhythm of arterial pressure. The pressure response to the cold pressor test (CPT), mental arithmetic test (MAS), and to dynamic and isometric effort was positive with both drugs, thus revealing a degree of protection offered by treatment using these two substances. In overall terms, the two drugs were well tolerated.

Adult↗
PubMed1992

Evaluation of the antihypertensive effect of once-a-day trandolapril by 24-hour ambulatory blood pressure monitoring. The Italian Trandolapril Study Group.

The aim of this study was to evaluate the effects of trandolapril on 24-hour blood pressure in patients with mild-to-moderate essential hypertension. After a washout period of 4 weeks, 42 patients were randomized to receive 2 mg of trandolapril once daily and 20 to receive placebo in a double-blind fashion for 6 weeks. This was followed by a second washout period of 4 weeks. At the end of each period, clinic blood pressure was assessed at 24 hours after the last dose and 24-hour ambulatory blood pressure was measured noninvasively, taking blood pressure readings every 15 minutes during the day and every 20 minutes during the night. Two patients were dropped out before any blood pressure evaluation under treatment. Analysis of ambulatory blood pressure was performed in 48 patients who met the criteria for the minimal number of ambulatory blood pressure data (2 values per hour during the day and 1 value per hour in the night). In the trandolapril-treated group (n = 41) clinic systolic/diastolic blood pressures were 159.8 +/- 2.0/102.4 +/- 0.8, 146.8 +/- 2.3/94.8 +/- 1.1, and 155.7 +/- 2.0/99.2 +/- 0.7 mm Hg in the pretreatment, treatment, and post-treatment periods, respectively. The corresponding values for 24-hour mean blood pressure (n = 31) were 139.5 +/- 1.9/91.2 +/- 1.5, 131.0 +/- 2.0/84.3 +/- 1.2, and 139.7 +/- 1.8/90.9 +/- 1.1 mmHg. The differences between the lower treatment, versus the higher pre- and post-treatment, values were all statistically significant (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Large artery compliance in essential hypertension. Effects of calcium antagonism and beta-blocking.

This study used 2D Doppler flowmetry to assess the effects on peripheral hemodynamics of effective treatment with nicardipine or atenolol in 40 patients with mild or moderate essential hypertension. Two groups of 20 patients received treatment with nicardipine or atenolol, respectively, for 8 months. Consequently, those patients considered to be responders (blood pressure less than 150/90 mm Hg) were monitored for another 4 weeks after the therapy was suspended in order to determine whether the changes, if any, in arterial compliance persisted. Following the 8-month therapy, four patients from each group were excluded from the study because of unsatisfactory blood pressure levels. After the treatment, there was a decrease in blood pressure in both groups (P less than .01). In the nicardipine group, there was a significant increase in diameter and compliance (P less than .01), whereas pulse wave velocity and resistance decreased (P less than .01). In the atenolol group, these parameters did not change significantly. After therapy was ended, blood pressure returned to baseline values in both groups. However, in the nicardipine group, the observed improvement in forearm hemodynamics persisted. This result may indicate that nicardipine is able to induce a regression of functional and/or structural changes in the large arteries of hypertensive patients.

Adrenergic beta-Antagonists↗