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Biomedical subjects

B Cesana

Publications and source records attributed to B Cesana.

At least 55 records · Page 3Linked to original sources

Folinic acid + 5-fluorouracil (5-FU) versus equidose 5-FU in advanced colorectal cancer. Phase III study of 'GISCAD' (Italian Group for the Study of Digestive Tract Cancer).

In a multicentre Phase III trial, 182 patients were randomized to either folinic acid (FA) (200 mg/sqm i.v. x 5 days) + 5-fluorouracil (5-FU) (400 mg/sqm i.v. in 15' x 5 days) every 4 weeks (Arm A), or to 5-FU alone at the same dosage (Arm B). Response rates were 20.6% (Arm A) and 10% (Arm B) with a significant (p = 0.046) advantage for FA + 5-FU. Median time to progression (6 and 6 months) and overall survival (11.5 and 11 months) were similar in the 2 groups of patients, while neither treatment was effective in reducing pain or improving performance status. Univariate analysis showed that no prognostic factors other than treatment influenced response, although survival was affected by the number and site of metastases, performance status, and the presence and degree of pain. Toxicity was acceptable and lower in comparison with other Phase II-III trials, with no significant difference between the 2 arms. However, in individual patients, grade 3-4 side effects (mainly stomatitis and diarrhoea) were observed, particularly in patients receiving FA: this led to interruption of the treatment in 7 cases. The superiority, in terms of objective response, of FA + 5-FU over 5-FU alone would seem to justify a large-scale evaluation of this combination in the adjuvant setting. Further improvements in relation to advanced disease (i.e., modifications to the schedule and/or introduction of other modulators) are warranted.

Adenocarcinoma↗

The impact of azathioprine and cyclosporine on long-term function in kidney transplantation.

To assess the impact of cyclosporine on long-term kidney function in transplant patients, we retrospectively analyzed 273 patients on azathioprine and 308 on CsA with graft functioning at 1 year. To balance the length of follow-ups, the observation of patients was cut at 5 years. Actual graft survival rate at 5 years was similar in Aza and CsA (88% vs. 90%). Multivariate analysis in Aza pts showed that proteinuria (P = 0.006) and hypertension at 1 year (P = 0.002) increased the probability of irreversible graft failure by 2.47 and 2.85, respectively. In CsA patients, proteinuria (P = 0.007) and plasma creatinine higher than 2.5 mg/dl (P = 0.006) increased the probability of graft failure by 5.12 and 6.48, respectively. In both Aza and CsA patients with a follow-up of at least 5 years, plasma creatinine levels were significantly worse at 5 years vs. 1 year (P = 0.004). The slopes of plasma creatinine values plotted vs time were not different between the two groups. Chronic graft dysfunction (CGD) was defined as a stable increase of plasma creatinine of at least 50% above stable values at 1 year. The probability of remaining without CGD at 5 years was 75% for CsA and 80% for Aza patients (P = N.S.). Multivariate analysis of factors influencing the development of CGD showed that hypertension (P = 0.003) and proteinuria at 1 year (P = 0.081) increased the probability of developing CGD by 2.19 and 1.76, respectively, in Aza, while in CsA patients proteinuria only (P = 0.063) increased the probability of developing CGD by 2.29. Graft survival at 5 years after development of CGD was 34% in Aza and 53% in CsA-treated patients. These data confirm that in the long-term CsA does not cause a higher prevalence of CGD and show that, in the presence of CGD, CsA has a superior protective effect than Aza.

Adult↗

Renal lithium clearance in the different stages of hypertension.

This study investigated whether fractional lithium excretion (FELi), used as a marker of proximal fluid delivery, changes during different phases of essential hypertension. Forty-eight subjects were studied: 12 essential hypertensives (EH); 12 borderline hypertensives (BL); 12 normotensives with a positive family history of essential hypertension (NH) and 12 normotensives without a family history of essential hypertension (NN). Measurements were performed in the recumbent position, both in basal conditions and after a saline load (2% body weight in 1 h; 0.333 ml/min per kg body weight). In basal conditions, a moderate extracellular volume expansion was already present in the subjects. In these conditions, FELi of EH was significantly higher than that of all the other groups (P less than 0.01). After the saline load, fractional sodium excretion increased in all the groups (P less than 0.01), but to a significantly greater extent in EH (P less than 0.01). FELi rose significantly only in BL (P less than 0.05). The change in FELi of BL correlated positively (P less than 0.02) with the change in blood pressure in 10 of these subjects 3 years after this study. Moderate extracellular volume expansion may be able to either reveal or stimulate an increase of FELi in subjects with established hypertension. When a greater degree of extracellular volume expansion is induced, this increases FELi in BL and this effect may be related to the subsequent development of hypertension.

Adolescent↗

Safety of ibopamine therapy in congestive heart failure. Ibopamine cohort study: baseline and 1-year results.

The study was designed to evaluate the safety of ibopamine (3,4-diisobutyryl ester of N-methyldopamine. SB(-)-505. Inopamil; CAS 66195-31-1) for the chronic treatment of congestive heart failure. It was conducted as a comparative cohort survey, versus digitalis. A third cohort was made with patients who received both drugs in association. Any differences between cohorts at baseline were dealt with by identifying explanatory variables with linear discriminant analysis and by performing multivariate statistical analysis by Cox's proportional hazard model. During 16 months, 3.330 patients were enrolled and then followed-up for a median time of 1 year. Baseline characteristics are reported as well as follow-up results on mortality, disease progression, anginal episodes, arrhythmias, need for cointervention and other undesired on-therapy events. Results pointing to efficacy are consistent with the favourable results from controlled randomized double blind medium--long term clinical trials. In addition, data from the present study do indeed provide strong evidence on the safety of long-term treatment with ibopamine. At variance with inotropic agents ibopamine did not increase mortality. The results rather suggest that long-term treatment with ibopamine affords an increase in survival and a delay in the progression of the disease, without adverse effects on cardiac rhythm and myocardial oxygen balance, and with a general improvement in the patients' quality of life.

Adolescent↗

IgA antigliadin antibodies, cellobiose/mannitol sugar test, and carotenemia in the diagnosis of and screening for celiac disease.

Serum IgA antigliadin antibodies (IgAAGA) assay, cellobiose/mannitol sugar permeability test (ST), and carotenemia were evaluated prospectively as diagnostic tests in 60 consecutive adult patients with suspected celiac disease (CD). CD was confirmed histologically in 26 patients. IgAAGA, ST, and carotenemia had a sensitivity of 65.4%, 96.2%, and 76.9%, a specificity of 97.1%, 73.5%, and 70.6%, and positive likelihood ratio of 22.2, 3.6, and 2.6, respectively. Multivariate logistic regression showed that IgAAGA and ST had a sensitivity and specificity of 96.2% and 70.6% and a positive likelihood ratio of 47.3 if both were positive. Assuming a prevalence of CD of 1:2000 in the general population, for every 89 positive IgAAGA and 549 altered ST there would be one celiac patient, whereas, if both tests were positive, the patient was certain to have CD. We conclude that, of the tests studied, IgAAGA and ST are respectively the most specific and the most sensitive and that, used together, they can diagnose CD.

Adolescent↗

Effects of blood donation on cerebral blood flow velocity.

Eighteen healthy male blood donors, nine with hematocrit (Hct) of 0.40 to 0.45 (normal Hct) and nine with Hct of 0.49 to 0.52 (upper-limit Hct), were monitored by continuous-wave internal carotid Doppler sonography and hematologic tests for 28 days after blood donation, to ascertain whether and to what extent a single standard donation may modify the velocity of cerebral blood flow. The two groups had similar mean predonation values of internal carotid flow velocity (ICFV): blood donation was followed in both groups by a slight, transient decrease of ICFV at the end of phlebotomy, due to donation-induced hypovolemia, and then by an increase of ICFV lasting 7 to 10 days. Analysis of individual profiles revealed that only four of nine upper-limit and six of nine normal Hct donors displayed a positive trend (increase) in the ICFV within the first week after donation, and that it was due mainly to a rise in systolic flow velocity. Mean Hct and arterial oxygen content showed a negative trend (decrease) within the first week that was opposite to the ICFV trend. Other laboratory variables, including serum proteins and plasma fibrinogen concentration, and the iron status indicators did not change, except for serum ferritin, which also decreased within the first week after phlebotomy. It can be concluded that blood donation may result in a short-term increase of blood flow velocity that is independent of Hct predonation levels in approximately one-half of the donors.

Adult↗

Double blind, controlled study of the efficacy and safety of alpidem in the treatment of anxiety in schizophrenic in-patients.

In this double-blind study, alpidem, a new imidazo-pyridine anxiolytic drug, was compared with placebo in order to test its efficacy and safety in chronic schizophrenic in-patients suffering from anxiety not directly related to the schizophrenic process. Sixty-six patients aged from 18 to 65 entered the trial. They also scored at least 18 on the Hamilton Rating Scale for Anxiety (HRSA) after a seven-day placebo run-in. Improvement in symptoms was evaluated by means of the HRSA, the Brief Psychiatric Rating Scale (BPRS), a Visual Analogue Scale (VAS), and the Clinical Global Impression score (CGI). Thirty-three patients were randomly allocated to alpidem and 33 to placebo. Alpidem was significantly more effective (P less than 0.0001) than placebo in improving HRSA scores (total score and factorial scores for somatic and psychic anxiety), BPRS, and VAS. Considering the results of CGI at 21 day, more patients were moderately to markedly improved on alpidem (30/33) than on placebo (2/33) (P less than 0.0001). The efficacy index, according to CGI, was significantly better (P less than 0.001 at least) for alpidem than for placebo. Side-effects were negligible in both groups.

Adult↗

Therapeutic effects of fengabine, a new GABAergic agent, in depressed outpatients: a double-blind study versus clomipramine.

The results of a double-blind clinical trial of fengabine vs clomipramine in depressed outpatients are reported. Fengabine, a new GABAergic agent, seems to be as effective as the reference drug, with a faster onset of action and a more marked effect on cognitive disturbances and retardation. The new drug is free of any significant anticholinergic or cardiovascular effect, and it is not sedative.

Adult↗

Double blind comparison of zolpidem 20 mg versus flunitrazepam 2 mg in insomniac in-patients.

The efficacy of zolpidem 20 mg was compared to that of flunitrazepam 2 mg. Forty-two insomniac female in-patients between 30 and 65 years of age were included in a double blind, parallel group trial and were randomly allocated to the two treatments. Study duration was 9 days with 2 days of placebo run-in, 5 days of active medication and 2 days of placebo withdrawal. Sleep latency, sleep duration, number of awakenings and time spent asleep during the night were given an ordinal score; condition in the morning was evaluated by Visual Analogue Scales and the psychomotor performance was evaluated by the tests: night-day for anterograde amnesia, digit span for verbal recall and Grünberger's fine motor function test. There was no significant difference between zolpidem and flunitrazepam for any of the variables; the drugs were significantly better than placebo baseline for all the sleep efficacy variables. The results of this study indicate that zolpidem is as effective as flunitrazepam in inducing and maintaining sleep but it does not induce a sense of weakness in the morning and does not impair memory.

Adult↗

Survival in cystic fibrosis: preliminary report from an Italian multicenter study.

An Italian multicenter study has been carried out in order to obtain data on survival and prognostic factors in CF. We report data from four CF Centers: Milan, Neaples, Cagliari, Rome, Anagraphic data, mode of presentation and of diagnosis were collected, using CFDB database, from 536 CF pts. 39 pts had meconium ileus (7.3%); 269 (50%) were diagnosed before 12 months of age. 27 pts were lost to follow-up (5%); and 65 pts died (12%). Statistical analysis was performed by Kaplan-Meier survival curves compared by Logrank test.

Adolescent↗

Predicting interindividual variations in antihypertensive therapy: the role of sodium transport systems and renin.

The efficacy of captopril at 75 mg/day, atenolol at 100 mg/day and canrenoate potassium at 200 mg/day was compared in 42 essential hypertensive patients in randomly assigned sequences. All the drugs lowered blood pressure significantly but variations were found in the individual response. Patients who were more responsive to captopril also seemed to be more responsive to atenolol and vice versa (r = 0.75; P less than 0.0001), while the relationship between mean blood pressure reached after canrenoate potassium and that reached after atenolol or captopril was much weaker. The patients who were responsive to atenolol and captopril were considered as one group (n = 22) and compared with the 12 patients more responsive to canrenoate potassium. Before treatment, the former group had higher plasma renin activity (PRA) and lower Na,K cotransport activity across the erythrocyte membrane than the latter. These two variables, considered together as a discriminant function, correctly classified 92% of cases in the canrenoate potassium responder group and 73% of cases in the atenolol-captopril responders. These results raise the problem of individual assessment to obtain the most effective antihypertensive therapy and suggest that PRA and Na,K cotransport may be useful in predicting the individual response to antihypertensive drugs.

Adolescent↗

Antihypertensive activity and duration of action of dilevalol in hypertensive patients at rest and during exercise. A comparison with captopril.

The aim of this study was to compare the effect of dilevalol and captopril on blood pressure and heart rate in hypertensive subjects, both at rest and during bicycle exercise. Thirty mild hypertensive patients (24 men, 6 women), aged 34-55, were studied in a randomized, double-blind, parallel group trial. After a 3-week placebo run-in, patients were randomized to receive either dilevalol (200 mg once daily) or captopril (50 mg twice daily) for 4 weeks. Dilevalol-treated patients whose diastolic blood pressure had not decreased by more than 8 mmHg from baseline (or to less than 95 mmHg) were given 400 mg once daily for a further 2 weeks. Treatment was stopped for all other patients. Blood pressure and heart rate were measured at rest and during bicycle exercise tests 4 ("peak") and 24 hours ("trough") after dosing in the dilevalol group and 4 ("peak") and 12 hours ("trough") after dosing in the captopril group. At the end of the placebo run-in, mean resting blood pressure was 156/102 mmHg in the dilevalol group and 157/103 in the captopril group. Six patients had blood pressure normalization with captopril and 9 with dilevalol 200 mg; a further 2 patients achieved normalized blood pressure levels with dilevalol 400 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Early and late prognosis in acute myocardial infarct. A retrospective study in patients admitted to the coronary care unit in the past 10 years].

The prognostic evaluation of the patient with an acute myocardial infarction is one of the most interesting unanswered problems. This is both because of its complexity and its implications in terms of secondary prevention. Several clinical studies have emphasized the reliability of the prognostic evaluation based on data collected during the first 24 hours. We therefore evaluated the prognostic relevance of 26 variables measured in the coronary care unit in 1914 patients admitted to our Unit as a result of acute myocardial infarction during the past 10 years. Twenty-four patients were lost to follow-up so that the evaluation refers to 1,890 patients, 1,506 of whom are males aged between 22 and 99 years (mean 58.1) and 384 are females aged between 29 and 88 years (mean 67.1); thus there is a greater prevalence of males. The sex-related difference in the age distribution is statistically significant. In-hospital mortality was analyzed using univariate and multivariate statistical methods (chi-squared test, multiple logistic regression analysis). The prognostic relevance of the considered variables in relation to the survival was analysed using the logrank test and using Cox's model. The variables associated with a greater risk of in-hospital death were found to be: age, presence of diabetes, anterior location of the infarct, arterial hypotension at admission, Killip class III and IV and the presence of ventricular tachyarrhithmias. In contrast, smokers had a lower in-hospital death risk. As to mortality during the follow-up, there was an association with age, female sex, pre-existent coronary disease, presence of high heart rate on admission, low peripheral tissue perfusion, x-ray documented pulmonary congestion, supraventricular tachiarrhythmias and intraventricular block. In contrast, the presence of obesity was associated with a reduced death risk during the follow-up. During the follow-up the most frequent cause of death was re-infarction, followed by sudden death, death from non-cardiac causes and heart failure.

Adult↗

A randomized trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy.

We conducted a controlled trial to investigate the long-term effects of treatment with methylprednisolone and chlorambucil in patients with idiopathic membranous nephropathy. We have previously reported that after a mean of 31 months, treated patients did better. We now report the results of a longer follow-up. Eighty-one patients with proteinuria (greater than or equal to 3.5 g per day) and biopsy-proved membranous nephropathy were randomly assigned to receive either supportive therapy alone or a six-month course of corticosteroids alternated with chlorambucil (0.2 mg per kilogram of body weight per day) every other month. Methylprednisolone was first given intravenously in three pulses (1 g per day) and was then given orally (0.4 mg per kilogram per day) for 27 days. The patients were followed for 2 to 11 years (median, 5). Two patients in the control group and one in the treatment group died. At the last follow-up visit, 9 of 39 patients assigned to the control group (23 percent) and 28 of 42 patients assigned to the treatment group (67 percent) did not have the nephrotic syndrome. At five years there were more remissions of the nephrotic syndrome in treated patients than in controls (22 of 30 vs. 10 of 25; P = 0.026). Compared with base-line values, the mean reciprocal of the plasma creatinine level declined significantly in the control group (33 percent; P = 0.0002) but not in the treatment group (6 percent; P not significant). Plasma creatinine increased by 50 percent or more in 19 controls (49 percent) and in 4 treated patients (10 percent). We conclude that a six-month course of methylprednisolone and chlorambucil can bring about sustained remission of the nephrotic syndrome and help to preserve renal function in patients with idiopathic membranous nephropathy.

Administration, Oral↗

A possible primary role for the kidney in essential hypertension.

The role of the kidney in "essential" or "genetic" types of hypertension has been evaluated both in a rat model such as the Milan hypertensive strain (MHS) or in humans. In both species, abnormalities of renal function have been demonstrated before the development of hypertension. Moreover hypertension could be "transplanted" with the kidney when kidney cross-transplantation was carried out between MHS and the Milan normotensive strain (MNS). Also in humans, the familiality for hypertension of the donor affected the requirement of antihypertensive therapy of the recipient. Further studies furnished results that were consistent with the hypothesis that a primary increase in Na transport across the tubular cell could be responsible for the pressor effect of the kidney in MHS or in humans. Because many similarities were found between the function of the tubular cell and the red blood cell in MHS, red blood cells were used to gain information about the molecular genetic mechanisms underlying these cellular changes. The results so far obtained showed that red blood cell abnormalities in MHS were genetically determined within the stem cells and genetically associated with the development of hypertension in F2 hybrids obtained by crossing the F1 (MHS X MNS). Moreover, the abnormal Na transport across the cell membrane may be due to an abnormal function of the membrane skeleton proteins. Studies are in progress to evaluate a possible cause-effect relationship between: membrane skeleton protein-ion transport across the cell membrane and the development of hypertension.

Animals↗

A double-blind, placebo-controlled study of alpidem, a novel anxiolytic of imidazopyridine structure, in chronically anxious patients.

In this double-blind study alpidem, a new imidazopyridine anxiolytic drug, was compared with placebo to assess its efficacy and safety in severely anxious patients at the fixed dose of 150 mg/day (50 mg t.i.d.) for 3 weeks. Fifty-nine patients with a score of at least 18 on the Hamilton Rating Scale for Anxiety (HRSA) entered the trial after a 3- to 7-day placebo run-in period. Symptom improvement was evaluated with the HRSA, the State and Trait Anxiety Inventory (STAI-1 and STAI-2), a Visual Analogue Scale (VAS) and the Clinical Global Impression (CGI). Alpidem was more effective than placebo in improving mean HRSA (total score and factorial scores for somatic and psychic anxiety), STAI-1 and STAI-2 and VAS scores. The efficacy index of the CGI was better for alpidem than for placebo. Side effects were negligible in both groups. Alpidem appears to be a new interesting anxiolytic drug devoid of significant sedative effects on mental functions.

Adjustment Disorders↗

Long-term outcome of patients with membranous nephropathy after complete remission of proteinuria.

To assess the prognostic significance of complete remission in patients with idiopathic membranous nephropathy, 33 patients were followed for a median of 96 months after remission of proteinuria. All patients had had a histological diagnosis of membranous nephropathy and a nephrotic syndrome. Only patients with a complete remission lasting for at least six months and with a follow-up of at least four years after remission were considered. No relapse of proteinuria developed in 17 patients (51%), 7 patients had relapse of non-nephrotic proteinuria (21%) and 9 (27%) relapse of nephrotic proteinuria. However proteinuria disappeared again in some patients so that at follow-up 73% of patients are in complete remission, 21% have non-nephrotic proteinuria and only 6% have nephrotic syndrome. All patients maintained a normal plasma creatinine over the years. It is concluded that complete remission of proteinuria is a strong predictor of long-term favourable outcome in patients with idiopathic membranous nephropathy.

Adolescent↗