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Biomedical subjects

C Rusconi

Publications and source records attributed to C Rusconi.

At least 19 recordsLinked to original sources
PubMed2006

QSAR study for a novel series of ortho disubstituted phenoxy analogues of alpha1-adrenoceptor antagonist WB4101.

On the basis of the affinities at the alpha1a-, alpha1b- and alpha1d-adrenoceptors and the 5-HT1A receptor of a previous series of sixteen 2-[(2-phenoxyethyl)aminomethyl]-1,4-benzodioxanes ortho monosubstituted at the phenoxy moiety, a number of ortho disubstituted analogues were designed, synthesized in both the enantiomeric forms and tested in binding assays on the same receptors. The affinity values of the new compounds 1-11 were compared with those of the enantiomers of the 2,6-dimethoxyphenoxy analogue, the well-known alpha1 antagonist WB4101, and of the ortho monosubstituted derivatives, suggesting some distinctive aspects of the interaction of the phenoxy moiety, in particular with the alpha1a-AR and the 5-HT1A receptor, of the monosubstituted and the disubstituted compounds. A classical quantitative structure-activity relationship (Hansch) analysis was applied to the whole set of the S enantiomers of the ortho mono- and disubstituted WB4101 analogues (26 compounds), finding a very good correlation for the alpha1a affinity. For this latter, a significant parabolic relationship was also found with the volume of the two ortho substituents. Diametrically opposite, the same relationships for the 5-HT1A exhibit low or insignificant correlation coefficients.

Adrenergic Antagonists↗
PubMed2005

Efficacy, toxicity and feasibility of a shorter schedule of DCEP regimen for stem cell mobilization in multiple myeloma.

From 2000 to 2004, 152 patients with multiple myeloma aged or=4 x 10(6) cells/kg. The proportion of patients in whom mobilization failed was similar in the two groups. The incidence of WHO grade III neutropenia was higher in group II, although the difference was not statistically significant; the percentage of patients requiring hospitalization for severe infections was similar in the two groups. The incidence of WHO grade IV thrombocytopenia did not differ between the two groups. The response rate was 72% in group I and 80% in group II with similar percentages of patients achieving good responses. DCEP-short is a good mobilizing regimen, sharing the same characteristics as infusional-DCEP: high mobilizing efficacy, low toxicity and good antitumor activity. This new schedule of DCEP does, however, allow complete outpatient management and so could be advantageously included in any high-dose therapy program.

Antigens, CD34↗
PubMed2004

Modification of thrombomodulin plasma levels in refractory myeloma patients during treatment with thalidomide and dexamethasone.

Deep venous thrombosis (DVT) has been variably reported in multiple myeloma patients during treatment with thalidomide alone or in combination with chemotherapy or dexamethasone. With the aim of investigating this complication, we performed, on a cohort of 13 relapsed refractory MM patients treated with low-dose thalidomide (100 mg/day) and dexamethasone (20 mg p.o./day for 4 days every 2 weeks), a serial evaluation of different laboratory parameters implicated in DVT. No significant abnormalities in all genetic, serologic, or plasmatic parameters studied were registered, apart from thrombomodulin which showed significant variations between baseline and 1st-month values and 1st- and 3rd-month values. In conclusion, the evidence of significant variations of thrombomodulin values in the 1st month of therapy, which is considered to involve the highest risk of thrombosis, might support a role for thrombomodulin in this complex mechanism.

Adult↗
PubMed2003

Urinary proteins in multiple myeloma: correlation with clinical parameters and diagnostic implications.

Renal failure is one of the worst complications occurring in multiple myeloma (MM) patients. It does not affect survival if reverted by a prompt chemotherapy before the damage becomes irreversible; therefore, the early diagnosis of renal dysfunction is crucial. High and low molecular weight urinary proteins have proved to be helpful in diagnosing initial renal damage since they are more sensitive than urea and creatinine serum levels or creatinine clearance. We studied the renal function of 111 MM patients through serum creatinine, urea, urinary IgG, alpha(1)-microglobulin (alpha(1)-M), and albumin (Alb). Two successive controls were made in a subset of 30 patients, categorized in three groups (improved, stable, worsened) according to the behavior of tumor burden markers (bone marrow plasmacytosis, monoclonal component, and beta(2)-microglobulin). In every group, we evaluated the behavior of urinary proteins. Renal dysfunction evaluated with serum parameters was present in 19 patients (17%), while if studied with urinary proteins was revealed in 71 patients (64.5%). Urinary proteins statistically correlated with each other. They correlated with creatinine, IgG, and alpha(1)-M also with urea. By contrast, they showed a variable correlation with clinical parameters: alpha(1)-M correlated with bone marrow plasmacytosis (BMPC) ( p=0.02) and beta(2)-M ( p=0.000001), IgG with all three disease parameters (MC p=0.0005, BMPC p=0.009, beta(2)-M p=0.007), and Alb only with beta(2)-M ( p=0.0004). In the subset of 30 patients followed with two successive controls, urinary proteins showed a parallel behavior with the indices of tumor burden. In conclusion, IgG, alpha(1)-microglobulin, and albumin are reliable and sensitive to precociously reveal renal damage, and we recommend their routine use for the definition and monitoring of renal function in multiple myeloma patients, mainly those in early stage, to better identify initial signs of progression.

Adult↗
PubMed2001

Prevalence of isolated left ventricular diastolic dysfunction in hypertension as assessed by combined transmitral and pulmonary vein flow Doppler study.

In a relatively large population of patients with treated systemic hypertension and normal left ventricular systolic function, prevalence of abnormalities of left ventricular diastolic function, as assessed by Doppler echocardiographic study of mitral and pulmonary vein flow, was high, with 51% of patients showing indirect signs of increased left ventricular end-diastolic pressure. Furthermore, our data documented that a "normal" mitral flow profile does not exclude the presence of an abnormality of left ventricular filling, which could be otherwise identified by combined analysis of a pulmonary vein flow profile.

Adult↗
PubMed2001

Generation of species cross-reactive aptamers using "toggle" SELEX.

Species cross-reactivity facilitates the preclinical evaluation of potentially therapeutic molecules in animal models. Here we describe an in vitro selection strategy in which RNA ligands (aptamers) that bind both human and porcine thrombin were selected by "toggling" the protein target between human and porcine thrombin during alternating rounds of selection. The "toggle" selection process yielded a family of aptamers, all of which bound both human and porcine thrombin with high affinity. Toggle-25, a characteristic member, inhibited two of thrombin's most important functions: plasma clot formation and platelet activation. If appropriate targets are available, the toggle strategy is a simple measure that promotes cross-reactivity and may be generalizable to related proteins of the same species as well as to other combinatorial library screening strategies. This strategy should facilitate the isolation of ligands with needed properties for gene therapy and other therapeutic and diagnostic applications.

Animals↗
PubMed2000

[Heart failure with conserved systolic function. Therapeutic potential with beta blocking agents].

It is increasingly recognized that the syndrome of congestive heart failure may occur in the absence of any abnormality of left ventricular systolic function. In this situation, the clinical picture of heart failure, particularly the presence of symptoms and/or signs of pulmonary congestion, is usually considered a consequence of an abnormal diastolic function of the left ventricle (diastolic heart failure). However, in the individual patient, several other potential causes should be taken into account before attributing to an isolated diastolic dysfunction of the left ventricle the pathogenetic role of clinical presentation. In fact, due to the current lack of validated criteria for diagnosis of diastolic heart failure, it still represents an exclusion diagnosis in the clinical setting. Prevalence of heart failure with preserved left ventricular systolic function is widely variable among the different studies, from 13% to over 70%, with most reports showing a prevalence of 30-40%. These differences depend on several factors, such as the criteria used for diagnosis of heart failure, as well as those used for recognizing a normal systolic function or the clinical setting considered (for example hospital versus community). According to an analysis of the studies published, heart failure with preserved left ventricular systolic function seems to be more common in the female sex and in elderly patients, and it is associated with hypertension and electrocardiographic or echocardiographic evidence of left ventricular hypertrophy. Atrial fibrillation, either paroxysmal or chronic, is common and may represent a precipitating factor of clinical deterioration. According to most studies, patients with preserved left ventricular systolic function show, compared to patients with reduced left ventricular systolic function, a better prognosis, as indicated by a lower mortality and hospital readmission rates. Regarding the therapy of these patients, it is known that there are virtually no well-controlled studies of the effect of pharmacological treatment on outcome. Accordingly, the therapeutic approach of heart failure with preserved systolic function is currently based on a careful pathophysiological interpretation of clinical picture in the individual patient.

Adrenergic beta-Antagonists↗
PubMed2000

[Diastolic function of the left ventricle and congestive heart failure with normal systolic function].

Mechanical performance of the heart depends on the physiologic interplay of its systolic and diastolic function. However, the cardiologist is used to defining left ventricular (LV) function only in terms of ejection fraction, cardiac output and blood pressure, thus observing only systolic function. In the last 10 to 15 years experience has revealed that, despite the presence of a normal LV systolic function, alterations of LV diastolic function may impair exercise tolerance and may be responsible for the clinical picture of about 30% of patients with a definite diagnosis of congestive heart failure. Doppler echocardiography has emerged as the most feasible and accurate noninvasive technique in assessing LV diastolic function in the clinical setting. Combined Doppler evaluation of transmitral and pulmonary venous flow velocity recordings, by transthoracic approach, allows us to obtain clinically relevant information on LV relaxation, LV filling, LV compliance, and LV end-diastolic and mean filling pressure, as well as on left atrial function, in more than 95% of patients referred to the echo-lab. With this combined evaluation different types of filling patterns have been identified. Clinical evaluation, together with structural/functional information obtained by M-mode and two-dimensional echocardiography, and mainly with detailed analysis of these LV filling patterns by Doppler, allow for a fairly accurate identification of various diastolic abnormalities, as well as the presence of diastolic dysfunction, i.e., increased filling pressures. Diastolic failure, characterized by the association of diastolic dysfunction and symptoms of pulmonary venous congestion, can now be more precisely identified following the criteria established by the Working Group on Diastolic Heart Failure of the European Society of Cardiology. Echo-Doppler age-adjusted normal values of indices of impaired LV relaxation and filling, along with cut-off values of Doppler signs of reduced compliance or increased filling pressures have been defined by the Working Group, and are herewith reported for practical purposes. Furthermore, as a reference for an advanced echo-lab, a "decalogue" of diastological performances is suggested.

Diastole↗
PubMed1999

Doppler echocardiographic assessment of hemodynamic progression of valvular aortic stenosis over time: comparison between aortic valve resistance and valve area.

BACKGROUND: Doppler-derived aortic valve resistance (AVR), i.e. the ratio between pressure gradient and flow rate, has been proposed as an alternative parameter to valve area (AVA) for assessing the hemodynamic severity of aortic stenosis (AS). There are no data on the evaluation of hemodynamic progression of AS using AVR. METHODS: Forty-five adult patients (24 women and 21 men, mean age 72 +/- 10 years) with AS were followed up for 18 months (range 6 to 45 months) with serial Doppler-derived AVR (Isaaz, JACC 1991; 18: 1661) and AVA (continuity equation). Rates of change of AVR and AVA over time were indexed for year of follow-up; furthermore, variations of these parameters during follow-up were expressed as percent change from baseline. RESULTS: During the follow-up period, AVA decreased from 0.74 +/- 0.28 to 0.6 +/- 0.17 cm2 (p < 0.05), with a rate of change of -0.1 +/- 0.13 cm2/year; AVR increased from 349 +/- 187 to 462 +/- 180 dyne/s/cm-5 (p < 0.05), with a rate of change of 79 +/- 69 dyne/s/cm-5/year. Variations observed in AVR, expressed as percent change from baseline, were larger than those observed in AVA (51 +/- 62% versus -16.5 +/- 15%). AVR percent change from baseline significantly correlated with AVA percent change from baseline (r = 0.83, p < 0.05). During follow-up, 6 patients showed no change in AVA: AVR was unchanged in 3 and increased in the remaining 3 patients (6, 11 and 58%, respectively), indicating a progression of AS severity that could not be appreciated from AVA alone. CONCLUSIONS: Serial changes in AVR, as assessed by Doppler echocardiography, significantly correlate with changes in AVA. Thus, the noninvasive assessment of AVR may be utilized in the evaluation of hemodynamic progression of AS and, in conjunction with AVA, may also provide complementary information for the management of these patients.

Adult↗
PubMed1998

Ventricular arrhythmias in adult aortic stenosis: prevalence, mechanisms, and clinical relevance.

With the longer life expectancy of the population, calcific aortic stenosis has become a common cardiac problem in the elderly. When patients with moderate to severe aortic stenosis become symptomatic, the prognosis is usually poor in absence of valve replacement and sudden death is a feared complication. It has been hypothesized that malignant ventricular arrhythmias could be responsible for the high incidence of sudden death in symptomatic patients with aortic stenosis. The purpose of this review is to analyze the prevalence, the electrophysiologic mechanisms, and the possible role of ventricular arrhythmias in the development of symptoms and in the outcome of adult subjects with aortic stenosis.

Adult↗
PubMed1997

Failure of low dosage thrombolytic therapy with streptokinase to treat heparin-induced thrombocytopenic-thrombotic syndrome.

We report the case of a 58-year-old man affected by thrombocytopenic-thrombotic syndrome induced by therapy with subcutaneous unfractionated heparin for superficial phlebitis of the left inferior limb. Thrombolytic therapy with low-dosage streptokinase, reported as successful in a previous case described by other authors, was inefficacious and the patient's outcome was unfavourable. Thrombocytopenic-thrombotic syndrome may be a dreadful and often deadly consequence of heparin therapy, and its treatment needs investigation, owing to currently broadening use of anticoagulant treatment with both unfractionated and low molecular weight heparins.

Anticoagulants↗