Search PubMed⌕ Search

Biomedical subjects

S Berti

Publications and source records attributed to S Berti.

At least 37 records · Page 2Linked to original sources

Normalization of peripheral thyroid hormone metabolism induced by successful chronic amiodarone treatment in patients with ventricular arrhythmias.

Amiodarone, an antiarrhythmic agent, is also known to have important effects on the peripheral metabolism of thyroid hormones; the relationship between these two effects of the drug, however, is not well established. We tested the hypothesis that the antiarrhythmic effect of amiodarone might be mediated by its effect on the metabolism of thyroid hormones. Peripheral thyroid hormone metabolism was investigated using a double-tracer ([125I]-T4 and [131I]-T3) procedure in 10 normal volunteers and 10 euthyroid patients with complex ventricular arrhythmias before and during 6 months' amiodarone treatment. The underlying cardiac disease was coronary artery disease in four cases, dilated cardiomyopathy in three and idiopathic arrhythmias in three. In all but one patient with complex ventricular arrhythmias amiodarone treatment resulted in a reduction of > or = 80% of premature ventricular contractions and complete suppression of episodes of ventricular pairs or ventricular tachycardia. In all cases successful treatment with amiodarone was accompanied by normalization of all kinetic parameters: T4 to T3 conversion ratio and T3/T4 molar ratio of production decreased to mean values of 24.7 +/- 17.5% and 0.35 +/- 0.22% respectively, whereas T4 production rate increased (mean value 75.9 +/- 30.0 nmol day-1 m-2). Our kinetic data indicate that long-term therapy with amiodarone, when effective in suppressing cardiac arrhythmias, also reduces peripheral T4 to T3 conversion, hence restoring the normal peripheral thyroid hormone metabolic pattern. In conclusion, our study confirms that the antiarrhythmic action of amiodarone may be (at least partially) mediated by its action on thyroid hormone metabolism, and may justify the hypothesis that an altered peripheral metabolism of thyroid hormones may play a role in the pathogenesis of complex ventricular arrhythmias.

Aged↗

Analytical performance and clinical usefulness of a commercially available IRMA kit for measuring atrial natriuretic peptide in patients with heart failure.

We evaluated the analytical characteristics and clinical usefulness of a commercially available IRMA kit for measuring plasma concentrations of atrial natriuretic peptide (ANP) in healthy subjects and in patients with heart failure. The method uses two monoclonal antibodies prepared against sterically remote epitopes of the ANP molecule; the first antibody is coated on the solid-phase beads, and the second is radiolabeled with 125I. Fifty-nine healthy subjects and 77 patients with heart failure were studied. After subjects had rested 20 min in a recumbent position, blood samples were collected from a brachial vein into ice-chilled disposable polypropylene tubes containing aprotinin and EDTA. Plasma samples were immediately separated by centrifugation and stored at -20 degrees C until assay. The working range (CV <15%) was 10-2000 ng/L. The detection limit (2.13 +/- 0.91 ng/L) was similar to those reported for other IRMAs but was much better than those of RIAs. For healthy subjects, the results of this method (18.0 +/- 10.6 ng/L, range 4.7-63 ng/L, median 16.7 ng/L, n = 59) were similar to those generally reported for the most accurate methods, i.e., those using preliminary extraction and chromatographic purification of plasma samples. Measured plasma ANP was significantly associated with the severity of clinical symptoms, i.e., NYHA class (ANOVA, P <0.0001), and with the left ventricular ejection fraction (n = 62, r = 0.618, P <0.0001). Patients with severe heart failure showed greatly increased values (NYHA III-IV: 257.4 +/- 196.6 ng/L, n = 23).

Adult↗

Altered tissue degradation and distribution of atrial natriuretic peptide in patients with idiopathic dilated cardiomyopathy and its relationship with clinical severity of the disease and sodium handling.

BACKGROUND: Atrial natriuretic peptide (ANP) has been suggested to play an important role in heart failure, preserving cardiorenal homeostasis through maintenance of the sodium balance and inhibition of the detrimental effects of the neurohormonal vasoconstrictor system. The current study was designed to investigate whether there is a disturbed renewal and distribution of ANP in patients with idiopathic dilated cardiomyopathy (IDC) with differing clinical severity of disease. METHODS AND RESULTS: We used a tracer method to perform a cross-sectional study of 15 IDC patients with differing clinical severity (New York Heart Association functional class I to III), prospectively divided into two groups according to their functional class (group 1, classes I and II; group 2, classes II-III and III). Eleven normotensive, nonobese male volunteers also were studied as a control group. Main ANP kinetic parameters were derived from the disappearance curve of the labeled hormone after the bolus injection of [125I]-labeled ANP. A high-performance liquid chromatography technique was used to separate the radiolabeled hormone in each plasma sample. Patients in group 1 showed higher ANP metabolic clearance rate (MCR) (2731.9 +/- 726.2 mL.min-1.m-2) than patients of group 2 (1718.4 +/- 621.2 mL.min-1.m-2) and control subjects (1873.1 +/- 551.2 mL.min-1.m-2). ANP disposal (MCR) positively correlated with biological hormonal effect (urinary sodium excretion) both in control subjects and in patients. In IDC patients of both groups, however, MCR values were always higher (approximately doubled) than the values found in control subjects at the corresponding sodium excretion. This finding indicates that a reduced ANP biological activity is associated with hormone degradation in patients. Moreover, patients of group 2 showed significantly higher ANP production rates (395.6 +/- 183.8 ng.min-1.m-2) than group 1 (166.0 +/- 139.0 ng.min-1.m-2) and control subjects (130.7 +/- 105.4 ng.min-1.m-2) despite a marked reduction in sodium excretion. Patients with IDC showed a progressive reduction in the total distribution volume (group 1, 19.8 +/- 5.8 L/m2; group 2, 12.7 +/- 6.9 L/m2; control subjects, 27.0 +/- 11.6 L/m2) of the hormone; this probably was due to a reduction in exchanges of ANP with peripheral tissues. CONCLUSIONS: Our study demonstrates a markedly altered degradation and distribution of ANP in patients with IDC, even in those at the early stage of clinical disease (classes I and II, group 1) who have ANP plasma levels in the normal range.

Adult↗

In vivo measurement of ANP overall turnover and identification of its main metabolic pathways under steady state conditions in humans.

Using a tracer method, we evaluated, in vivo, the main turnover parameters and the main metabolic pathways of ANP in 10 normal subjects. HPLC was used to purify the labeled hormone and the principal labeled metabolites present in venous plasma samples collected at determined times after tracer injection. The main ANP kinetic parameters were derived from the disappearance curves of [125I] ANP, which were satisfactorily fitted by a biexponential function in all subjects. Newly produced ANP initially distributes in a large, plasma equivalent space (10.9 +/- 3.6 l/m2 body surface); the hormone rapidly leaves this space due to both degradation and to distribution in peripheral spaces. The mean residence time in the body (19.4 +/- 19.8 min) and the plasma equivalent total distribution volume (28.2 +/- 11.5 l/m2) indicate that ANP is also widely distributed outside the initial space in humans (circulating ANP is no more than 1/15 of the body pool). Metabolic clearance rate values were distributed across a wide range (from 740 ml/min/m2 to 2581 ml/min/m2, mean 1849 ml/min/m2), and were shown to strongly correlate (R = 0.962) with the daily urinary excretion of sodium. A complete separation of labeled ANP from its labeled metabolites was achieved by the HPLC technique; at least 3 different peaks due to labeled metabolites in vivo produced from the injected [125I]ANP1-28 were found. The first chromatographic peak eluted showed an identical elution time to monoiodotyrosine. At least two other peaks due to in vivo generated labeled metabolites were well identified in the chromatograms: one peak (coeluting with labeled COOH-terminal tripeptide, H-Phe-Arg-Tyr-OH) was eluted ahead and one (coeluting with labeled peptide fragments ANP7-28, ANP13-28, and ANP18-28) behind the elution peak of the labeled ANP. The peak of labeled tyrosine appearing in the plasma ranged between 3 and 5 min after tracer injection; the other two peaks of radioiodinated metabolites showed their highest activity in the first sample (1.5 min), suggesting an earlier occurrence of their peaks. These labeled metabolites seem to be intermediate peptides, between the intact circulating form of the hormone and the final labeled metabolite (tyrosine), which is the last amino acid of the peptide hormone, produced in vivo after injection of the tracer.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Measurement of serum amiodarone and desethylamiodarone by HPLC: its usefulness in the follow-up of arrhythmic patients treated with amiodarone.

Amiodarone is an antiarrhythmic agent used for the treatment of supraventricular and ventricular arrhythmias. Owing to its narrow therapeutical range, monitoring of drug concentration is mandatory. The circulating and tissue levels of amiodarone and of its main endogenous metabolite, N-desethyl-amiodarone, are currently measured by means of HPLC procedures, which are tedious and time-consuming, and often beset with problems and drawbacks. We have developed a new chromatographic assay for the simultaneous measurement of amiodarone and N-desethyl-amiodarone in serum samples, and tested its usefulness in the follow-up of 14 patients (8 men and 6 women, age range 40-65 years) with complex ventricular arrhythmias, treated with amiodarone for at least 5 weeks. This assay uses trifluoperazine dihydrochloride as internal standard and a preliminary extraction of serum samples with isopropyl ether. The assay procedure was the following: 350 microliter patient's serum, to which 1 microgram trifluoperazine was added, were extracted with 280 microliter isopropyl ether. After mixing and centrifugation, 50 microliter of the organic layer were filtered and then injected onto the HPLC system (15 cm x 3.9 mm Resolve 5-micrometer spherical silica column); the elution rate was 1.8 ml/min (mobile phase, 920 ml of methanol and 80 ml of ammonium sulfate buffer) in isocratic condition. The time for a complete assay of each serum sample was less than 20 min, and its working range was 0.1-5.0 microgram/ml of amiodarone. An excellent recovery of the drug from subtherapeutical values up to toxic amiodarone concentration was obtained. The intra-assay precision of amiodarone assay ranged form 5 to 11%, while the between-assay precision administered in all patients, without increasing the amiodarone concentration beyond the toxic threshold level. The plateau of the circulating levels of the drug was generally reached in about 5-12 days, at the acceptable therapeutical range, from 0.5 to 2 microgram/ml. In conclusion, this chromatographic method for the assay of serum amiodarone levels is sufficiently simple, rapid and reliable to be considered a useful tool in the follow-up of arrhythmic patients chronically treated with amiodarone.

Adult↗

[Treatment of large bowel obstruction. Experience with intra-operative wash-out of the colon].

The treatment of colorectal obstructions is a surgical problem. The surgeon can choose between primary resection with anastomosis and the staged operations. The one stage procedures need colon decompression or intraoperative colonic lavage. In our experience between 1990 and 1993, 23 patients required an emergency intervention for colon obstruction; between them 13 patients were affected by a left colonic obstruction and were treated with a staged procedure (like Hartman operation) in 9 cases and with intraoperative colonic wash-out with primary anastomosis in 4 cases. The last group had a good postoperative course without an increased incidence of anastomotic leakage (no one in our limited experience). Compared with staged surgery, immediate resection and anastomosis had significant advantages for the patients because: 1) the quality of the life is better (absence of colonstomy); 2) the cumulative hospitalization is reduced (15 days vs 32 days); 3) there is a reduction in operative risk and in the cumulative intra- and postoperative immunodepression. The correct evaluation of the effect on the long-term survival of these factors needs larger series and of longer follow-up.

Colonic Diseases↗

Kinetic study of atrial natriuretic peptide in patients with idiopathic dilated cardiomyopathy: evidence for resistance to biologic effects of the hormone even in patients with mild myocardial involvement.

Atrial natriuretic peptide (ANP) kinetics was studied in 12 patients with idiopathic dilated cardiomyopathy at different sodium excretion (30-175 mmol/day) and variable degrees of hemodynamic dysfunction [New York Heart Association (NYHA) class range I-III] to investigate whether differences in renewal and distribution of this hormone (as compared with those of a control group) play a role in pathogenesis and evolution of heart failure. [125I]Labeled ANP was injected as a bolus, and a high-performance liquid chromatography (HPLC) procedure was used to purify the labeled hormone in venous plasma samples collected for < or = 50 min after injection; the main ANP kinetic parameters were then derived from the disappearance curve of the labeled hormone. As in controls, a positive linear regression between ANP metabolic clearance rate (MCR, ml/min/m2) values and daily urinary excretion of sodium (NaUE, mmol/day) was noted in patients. The different linear regression coefficients between normal subjects (MCR = 365 +/- 8.08 NaUE, r = 0.986, p < 0.0001) and patients (MCR = 497 + 18.5 NaUE, r = 0.867, p = 0.001) indicate that in patients a higher peptide clearance rate is needed to obtain the same biologic effect (sodium excretion) and suggest that resistance to biologic effects of the hormone exists in patients at an early stage of disease (NYHA class I). When the efficiency of the ANP system in excreting sodium was expressed as the ratio of NaUE to ANP production rate (PR = MCR x ANP plasma concentration, microgram/day/m2) patients showed significantly lower values (p = 0.0126) than normal volunteers, thus confirming resistance to the hormone effects. Significantly lower values for ANP total distribution volume (16.5 +/- 8.4 L/m2), mean residence time in the sampling space (4.04 +/- 1.14 min), mean residence time in the body (7.25 +/- 2.13 min), and fewer recycles through the initial (sampling) space (0.27 +/- 0.16) were noted in patients, indicating an altered mechanism regulating distribution of the hormone. The positive correlations between ANP MCR (L/min/m2) values and cardiac index (CI, L/min/m2) (MCR = -1.24 + 1.17 CI, r = 0.689, p = 0.0092) and between initial distribution volume (IDV, L/m2) and CI (IDV = -11.2 + 6.85 CI, r = 0.730, p = 0.0046) in all patients indicate that hemodynamic factors contribute to the progressive reduction in MCR and IDV values throughout the progression of myocardial involvement.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

ANP kinetics in normal men: in vivo measurement by a tracer method and correlation with sodium intake.

125I-labeled atrial natriuretic peptide (ANP) was bolus injected into seven healthy human male subjects on an unrestricted diet (sodium intake ranging from 80 to 300 mmol/day). A high-performance liquid chromatographic procedure was used to purify the labeled hormone and the principal labeled metabolites in venous plasma samples collected up to 50 min after injection. The main ANP kinetic parameters were derived from the disappearance curves of the 125I-ANP, which were satisfactorily fitted by a biexponential function in all subjects. Newly produced ANP initially distributes in a large space (plasma-equivalent volume is 12.1 +/- 3.6 l/m2 body surface); the hormone rapidly leaves this sampling space through both degradation and distribution in peripheral spaces, as indicated by the single-pass mean transit time through the sampling space (3.9 +/- 1.2 min). The mean residence time in the body (22.7 +/- 23.1 min) and the plasma-equivalent total distribution volume (30.9 +/- 12.0 l/m2) indicate that ANP is also widely distributed outside the initial space. Metabolic clearance rate (MCR) values were distributed across a wide range (from 740 to 2,581 ml.min-1 x m-2) and were shown to correlate strongly with the daily urinary excretion of sodium. These results indicate that: 1) newly produced ANP is rapidly distributed and degraded, 2) the body pool of the hormone can be considered as a combination of two exchanging spaces, 3) circulating ANP is < or = 1/15 of the body pool, and 4) MCR of ANP is closely related to sodium intake, at least in normal subjects on a free sodium intake diet.

Adult↗

Histologic evidence of myocardial damage in apparently healthy subjects with ventricular arrhythmias and myocardial dysfunction.

The association of ventricular arrhythmias and myocardial dysfunction could be considered an early step toward cardiomyopathy; therefore, we studied 28 patients in NYHA class I and II, characterized by complex ventricular arrhythmias (VA) on 24-h Holter monitoring and volumetric and/or contractile abnormalities on a standard two-dimensional echocardiogram (2-D echo). All patients underwent radioisotopic angiography, 20 patients complete hemodynamic study, and 15 patients endomyocardial biopsy. Ambulatory ECG monitoring showed the presence of frequent premature ventricular contractions in 14 patients (50%) and episodes of ventricular tachycardia in 16 patients (57%). 2-D echo showed mono- or biventricular enlargement and dyssynergies in 25 patients (89%) (left ventricle in 6, right ventricle in 11, both in 8). Two patients showed only left ventricle enlargement and one patient isolated left ventricular dyssynergies. Radioisotopic angiography showed mono- or biventricular ejection fraction reduction in 24 patients (85%) and regional dyssynergies in 24 patients (85%) in accordance with 2-D echo. Hemodynamic study showed in all patients normal coronary arteries, and right and left angiography confirmed enlargement and/or regional dyssynergies. Endomyocardial biopsy was abnormal in 11 of 15 patients: various degrees of hypertrophy, parcellar fibrosis, and adipogenic infiltration were found. Our preliminary data suggest that the simultaneous occurrence of ventricular arrhythmias and ventricular dyssynergies and/or enlargement in patients without apparent clinical heart disease may represent an early stage of dilated cardiomyopathy.

Adolescent↗

Atrial natriuretic peptide during different pacing modes in a comparison with hemodynamic changes.

The study investigates the response of atrial natriuretic peptide (ANP) to different cardiac pacing modes in comparison with hemodynamic changes. Ten patients underwent Swan-Ganz catheterization during pacemaker implant. Atrioventricular and ventricular pacing were performed consecutively at three pacing rate levels (80, 100, and 110 ppm). Blood samples were taken from the pulmonary artery for ANP determination, both basally and at the end of each pacing period. Concomitantly, mean pulmonary capillary wedge pressure (PCWP) and mean pulmonary artery pressure (PAP) were measured. Cardiac output (CO) was determined by thermodilution both basally and during the 110 ppm steps. During atrioventricular pacing, whereas no significant changes were observed for ANP, PCWP and PAP, CO increased significantly (P less than 0.0005). At the beginning of ventricular pacing hemodynamic parameters and ANP levels were comparable with those of baseline conditions. During subsequent ventricular pacing PCWP and ANP increased significantly at the 110 ppm rate step (P less than 0.05). PAP did not change significantly, whereas CO decreased in all cases (P less than 0.01). A positive correlation was observed between ANP and PCWP during ventricular (P less than 0.001), but not atrioventricular pacing. The results, while confirming the hemodynamic advantages of atrioventricular pacing, point to a major stimulation of ANP secretion during ventricular pacing. This fact, together with the observed drop in CO and the correlation between ANP and PCWP, suggest that the increase of ANP in ventricular pacing may be the expression of a compensatory mechanism to the hemodynamic disadvantages of atrioventricular asynchrony.

Aged↗

[Ambulatory electrocardiography in the screening of patients with palpitations].

The role of 24 hour Holter monitoring in the screening of patients complaining of palpitations is reviewed. The term "palpitations", although not always unequivocally used, implies the presence of an arrhythmia. The clinical-instrumental correlation of an intermittent symptom is made possible by continuous electrocardiographic monitoring. Answers to be expected from a 24 hour Holter monitoring in order to achieve an early characterization of the arrhythmia are related to: site of origin, incidence, circadian distribution, prognostic stratification, events aggregation, presence of other asymptomatic abnormalities (rhythm, ST-T).

Arrhythmias, Cardiac↗

Sequential behaviour of extracellular matrix glycoproteins in an experimental model of hepatic fibrosis.

The behaviour of extracellular matrix glycoproteins (fibronectin, laminin, basement membrane heparan-sulphate proteoglycan, type III, IV and V collagens) has been investigated in a sequential model of experimental hepatic fibrosis, using an immunofluorescence technique. The presence of some basement membrane macromolecules (such as type IV and V collagens, laminin and basement membrane heparan-sulphate proteoglycan) is detectable only in the early stages of septa formation, while type III collagen and fibronectin persist in late septa. These data suggest that hepatic fibroplasia proceeds through different steps in which stromal glycoproteins are preferentially engaged, as happens during organogenesis.

Animals↗