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Biomedical subjects

A Clerico

Publications and source records attributed to A Clerico.

At least 55 records · Page 3Linked to original sources
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

Cytomegalovirus-associated stage 4S neuroblastoma relapsed stage 4.

Neuroblastoma is one of the most frequent solid tumors in childhood, rarely recurrent after five years from diagnosis. Cytomegalovirus (CMV), a major pathogen causing congenital birth defects and severe opportunistic diseases, has been shown to have teratogenic, immunodepressive and oncogenic properties. The case of a girl with stage 4S neuroblastoma diagnosed at three months and relapsed as stage 4 five years later is reported. In both circumstances, active CMV infection was revealed by positive CMV-specific IgM and IgA antibodies, CMV-DNAemia and CMV culture. At three months, the patient presented with subcutaneous nodules, hepatosplenomegaly and increased aminotransferase levels, and the opsolonus-myoclonus syndrome. Mental retardation developed later on. At 5 years, relapsed neuroblastoma was preceded by a mononucleosis-like syndrome concomitant with active CMV infection and decreased levels of immune cells and natural killer activity. Clinical, virologic, and immunologic findings suggest an immune-mediated pathogenic role for CMV in this tumor.

Abdominal Neoplasms↗
PubMed1995

Does chemotherapy have a role in low-grade astrocytoma management? A report of 13 cases.

Surgery is the treatment of choice for low-grade astrocytoma while radiotherapy is carried out only when total resection is not possible. This study assessed the effectiveness of chemotherapy in nonresectable cases. Thirteen children with nonresectable astrocytoma were treated with carboplatin and etoposide and after four cycles the response to treatment was evaluated according to radiologic criteria. The results were: one with complete response (CR), three with minor response (MR), six with stable disease (SD), and three with progressive disease (PD). Moreover, in 77% there was an improvement in the neurologic picture. In particular, two cases with hypothalamic astrocytoma showed a regression of the diencephalic syndrome following chemotherapy. In six cases chemotherapy was carried out, at reduced dosage, after the first four cycles either because there was clinical improvement or because it was necessary to postpone radiotherapy in very young patients. After a follow-up period ranging between 11 and 63 months (average: 30 months), nine of the 13 patients are alive (69%) while four died of disease progression. Further studies would be useful to evaluate the role of chemotherapy in the management of low-grade astrocytoma.

Adolescent↗
PubMed1995

Pressor, renal and endocrine effects of L-arginine in essential hypertensives.

The pressor, renal and endocrine effect of the physiological precursor of endothelial derived nitric oxide, L-arginine was compared, with a substrate inactive on nitric oxide, hypertonic D-glucose, in hypertensive patients. Ten mild-moderate essential hypertensives were assigned to either L-arginine (n = 5) or D-glucose (n = 5). Substances were infused over 25 min at equiosmolal rates preceded and followed by saline infusion for 25 min. Blood pressure and heart rate were monitored at 3-min intervals, while hormonal and humoral variables, inulin and paraaminohippurate clearance and electrolyte excretion were measured at the end of each period under conditions of maximal diuresis. L-arginine and D-glucose increased serum osmolality comparably and caused similar haemodilution to that with control saline. During L-arginine infusion, systolic and diastolic blood pressure decreased by 16.6% and 11%, respectively, and recovered in the postinfusion period. Heart rate, plasma renin activity, and plasma noradrenaline did not change significantly. The percent blood pressure decrement induced by L-arginine was significantly greater than that by D-glucose. Glomerular filtration rate was stable and renal plasma flow was increased by both substances. However, natriuresis, kaliuresis and chloruresis were markedly stimulated only by L-arginine, which also promoted the development of systemic acidosis, possibly as a consequence of hydrochloridric acid generated during its metabolism. Circulating insulin, atrial natriuretic peptide, growth hormone and glucagon levels were increased and plasma aldosterone was unchanged during infusion of L-arginine. Insulin was stimulated and the other hormones inhibited during infusion of D-glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗
PubMed1995

Preparation of mono-radioiodinated tracers for study of the in vivo metabolism of atrial natriuretic peptide in humans.

In the present paper we evaluate the optimum chemical conditions for labelling atrial natriuretic peptide (ANP) and its metabolites and for preparing highly purified radiotracers which can be used for in vivo kinetic studies of ANP in humans. Synthetic alpha h1-28ANP and some hormone metabolites were iodinated with Na125I or Na131I by means of the lactoperoxidase (ANP) or the chloramine-T (ANP metabolites) technique. The biological activity of labelled ANP was tested by means of a binding study using mouse cardiac membranes. A high-performance liquid chromatography (HPLC) procedure was used to purify the labelled hormone and the principal labelled metabolites in venous plasma samples collected up to 50 min after the injection of 125I-labelled ANP from nine healthy men. 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. The main advantages of this tracer technique are: (1) high accuracy, allowing the identification of the metabolites produced in vivo under steady-state conditions after injection of the precursor (labelled hormone); (2) high sensitivity, allowing the detection of minimal quantities of metabolites (that cannot be identified on the basis of the integrated areas from the ultraviolet-absorbing peaks on HPLC); (3) high specificity, allowing the detection of possible in vitro artefactual generation of cleavage products of ANP using an internal labelled standard. Utilizing this tracer method, it was possible to estimate the principal parameters of ANP kinetics and also to plot the appearance curves of the labelled metabolites produced in vivo after the injection of the labelled precursor.

Adult↗
PubMed1995

Effects of different types of anti-aging dietary restrictions on age-related atrial natriuretic factor changes: an immunochemical and ultrastructural study.

The effects of two types of anti-aging dietary restrictions restrictions-60% diet restriction (DR) and every-other-day feeding (intermittent feeding, IF)-on age-related changes in atrial natriuretic factor (ANF) metabolism were studied in male Sprague Dawley rats by standard radioimmunological procedures and transmission electron microscopy. Both diet restrictions decreased plasma ANP (atrial natriuretic peptide) levels significantly (12-month-old rats: ad libitum fed controls 96 +/- 17.3 pg/mL, IF 63 +/- 4.8 pg/mL, DR 74 +/- 14.4 pg/mL; 24-month-old rats: AL 109 +/- 6.3 pg/mL, IF 75 +/- 8.9 pg/mL, DR 65 +/- 9.1 pg/mL). Dietary restriction prevented the age-related increase in ANP concentration in both the right atrium (12-month-old rats: AL 0.25 +/- 0.033 microgram/mg, IF 0.22 +/- 0.023 microgram/mg, DR 0.30 +/- 0.044 microgram/mg; 24-month-old rats: AL 0.39 +/- 0.037 microgram/mg, IF 0.10 +/- 0.015 microgram/mg, DR 0.07 +/- 0.011 microgram/mg) and left atrium (12-month-old rats: AL 0.23 +/- 0.033 microgram/mg, IF 0.13 +/- 0.019 microgram/mg, DR 0.17 +/- 0.035 microgram/mg; 24-month-old rats: AL 0.44 +/- 0.037 microgram/mg; IF 0.07 +/- 0.009 microgram/mg, DR 0.07 +/- 0.011 microgram/mg). Endocrine cardiocytes of diet-restricted senescent rats could be readily distinguished ultrastructurally from cells of ad libitum fed controls due to a higher number of beta-atrial specific granules of lower electrondensity. In conclusion, anti-aging diet restriction regimens fully prevented the age-related increase in the hormone store in atrial tissue, and lowered plasma ANP levels.

Age Distribution↗
PubMed1995

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↗
PubMed1995

Alterations in metabolic clearance of atrial natriuretic peptides in heart failure: how do they relate to the resistance to atrial natriuretic peptides?

Deficiencies in activity of the atrial natriuretic peptide (ANP) system may be able to explain the disturbed electrolyte and fluid homeostasis occurring in chronic heart failure. Generally, in studies concerning the possible pathophysiologic role of ANP in heart failure, only the circulating levels of the hormone were measured. It has been shown, however, that plasma ANP levels exhibit marked variability attributable to the pulsatory pattern of secretion and to its very short plasma half-life. An evaluation of the main turnover parameters might represent a significant improvement in the assessment of the functioning of the overall ANP system. By using a tracer method, which does not alter the steady-state condition, a disturbed peripheral metabolism of ANP and a resistance to its biologic effects was demonstrated in patients with idiopathic dilated cardiomyopathy, even in those in the asymptomatic phase of the disease, showing ANP circulating levels, atrial pressure and volume, and cardiac index within the normal range. The altered degradation and distribution of ANP in patients with heart failure were demonstrated by a great increase in metabolic clearance (on average, 2.5-fold), production (on average, 6-fold), or both, and by a progressive reduction in the distribution spaces of the hormone when compared with normal subjects at the same sodium intake. The ratio between ANP disposal and the daily excretion of sodium (equal to the sodium intake in subjects at a strictly controlled sodium balance) may give a good index of the biologic activity (natriuresis) of the ANP system. Preliminary studies suggest that an index of biologic activity of the ANP system may be a useful tool for the comparison of the efficacy of different therapeutic strategies in heart failure. Indeed, after a 2-month treatment with an angiotensin-converting enzyme inhibitor, this index was returned to within the normal range, suggesting that the drug was able to "normalize" the peripheral distribution and degradation of the hormone in these patients. Although future studies in a large series of patients will be useful to assess this important issue, the setup of accurate methods able to evaluate the presence and degree of resistance to biologic activity of ANP may be a useful tool in the follow-up evaluation of patients with heart failure, and may pave the way for further progress in the knowledge of more general physiologic and pathophysiologic mechanisms of this important clinical condition.

Animals↗
PubMed1995

Evaluation of the endocrine function of the heart in humans: proposal for an integrated approach for the assessment of production, secretion, distribution and degradation of atrial natriuretic factor and related peptides.

It has become established that heart has an endocrine function because it synthesizes and secretes a family of peptide hormones, called Atrial Natriuretic Peptide (ANP), with potent diuretic, natriuretic, vascular smooth muscle-relaxing activity and complex interactions with the hormonal and nervous systems. Because ANP has important volume-regulatory characteristics, it is postulated to play a central role in volume homoeostasis under normal conditions and in several pathophysiological states, such as congestive heart failure. ANP is able to counterbalance all the detrimental effects of activation of the neuro-hormonal system in patients with heart failure may lead to new therapeutical protocols that can prevent the progression from compensation to overt heart failure. An integrated approach for the assessment of the endocrine function of the heart is proposed, consisting of four different, but complementary, steps: 1) evaluation of gene expression of ANP in the myocardial cell; 2) determination of circulating and tissue levels of ANP; 3) in-vivo assessment of the main turnover parameters of the hormone; 4) studies on localization and identification of ANP receptors. These procedures have been employed in physiological, pharmacological and/or clinical studies. The development and the standardization of new methods for the assessment of endocrine function of the heart will not only increase our understanding of the physiological regulation of production, secretion, and function, and of the pathophysiological role of ANP and its related peptides, but also may pave the way for further progress concerning our knowledge of more general physiological and pathophysiological mechanisms of the cardiovascular system itself.

Amino Acid Sequence↗
PubMed1995

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↗
PubMed1995

Determination of endothelin binding sites in bovine atrium and ventricle membranes: a model for binding studies in human cardiac tissue.

The characterization of the binding sites of endothelin (ET) could constitute a useful tool to better understand its role in different pathophysiological conditions in human myocardial tissue. Crude membrane fractions were prepared from bovine atrium and ventricle for binding-assay assessment; membranes were also prepared from portions of atrium or ventricle < 100 mg each, a size comparable with human surgical fragments, and Scatchard analysis was performed from each single fragment. Portions of cardiac tissue were homogenized in 10 volumes of Tris/HCl buffer, 50 mM, pH 7.4, containing protease inhibitors; the supernatant was centrifuged at 50,000 x g for 30 min and the pellet stored at -80 degrees C. 125-I-ET-1 binding was performed by using 50 micrograms of protein and scalar concentrations of radioligand (8-200 pM), at 37 degrees C for 4 h and was stopped by filtration through a glass-fibre filter. The specific binding was saturable (at 200 pM of 125-I-ET-1 for 100 micrograms/ml of protein); the equilibrium was reached in 4 h at 37 degrees C at a radioligand concentration of 150 pM; a similar pattern, but a lower binding was obtained at 4 degrees C and 25 degrees C; the binding linearly increased with protein concentrations from 12.5 to 150 micrograms, and saturated at higher concentration. Non-specific binding was determined in presence of 0.1 microM unlabelled ET-1 and was about 2% of the total radioactivity added, for 125-I-ET-1 ranging from 8 to 200 pM, at 100 micrograms/ml of protein. By Scatchard analysis Kd proved to be 20.7 +/- 3.9 and 19.9 +/- 0.6 pM, Bmax 42.4 +/- 12.7 and 59.3 +/- 13.0 fmol/mg of protein, for atrium and ventricle respectively. Differential inhibition of binding was observed for the three ET isoforms; IC50 were similar for atrium and ventricle and proved to be 50 nM for ET-1 and ET-2 and > 200 nM for ET-3. This latter finding and the Scatchard analysis suggest the presence of a single class of binding sites in bovine cardiac membranes. No significant differences in absolute values of Kd and Bmax were found when cardiac membranes were obtained by small tissue fragments.

Animals↗
PubMed1994

Changes in endocrine atrial rat cardiocytes during growth and aging: an ultrastructural, morphometric and endocrinological study.

The effects of age on atrial natriuretic factor (ANF) metabolism were studied in male Sprague Dawley rats by standard radioimmunological procedures, transmission electron microscopy, and ultrastructural morphometry. Plasma atrial natriuretic peptide (ANP) levels increased during growth (1-month-old rats: 64 +/- 8.7 pg/mL; 2-month-old rats: 105 +/- 8.1 pg/mL) and did not change thereafter. Immunoreactive (ir)-ANP concentration increased significantly in senescent rats, both in the right (12-month-old rats: 254 +/- 33 ng/mg; 24 month-old: 415 +/- 77 ng/mg) and left atrium (226 +/- 30 and 498 +/- 60 respectively). The ultrastructural morphological features of the endocrine cardiocytes of senescent rats were the presence of a few lysosomal structures and atrial specific granules of higher electron-density. Ultrastructural morphometry studies did not reveal any significant increase in the number or in the mean individual volume of atrial specific granules, compared with young adult rats. In conclusion, unlike younger rats, morphometric data in older and senescent rats show that atrial granularity may not necessarily change together with atrial ir-ANP contents; ir-hormone assay findings show that senescent rats have ANP plasma levels within the norm, and a much larger hormone store in atrial tissue.

Aging↗
PubMed1994

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↗
PubMed1994

Analytical performance of CA 19.9, CA 125 and CA 15.3 assays as observed through an external quality assessment program.

Immunoassays of the tumor markers CA 19.9, CA125 and CA 15.3 are generally acknowledged to be a useful tool in the management of cancer patients. As a consequence, many methods developed by different companies are now commercially available. However, discrepancies have been described in the results of marker determinations even when the same monoclonal antibody was used. An external quality assessment (EQA) was carried out; starting from 1989 about 110 laboratories participated; since December 1991 the program was linked with the interlaboratory program Oncocheck organized by the Service de Radiopharmacie et Radioanalyse, University of Lyon. At present more than 200 laboratories of many European countries are involved: cumulatively 47 quality control samples have been prepared and sent to the participants. This manuscript is a report on data collected for CA 19.9, CA 125, and CA 15.3.

Analysis of Variance↗
PubMed1994

Critical evaluation of endothelins assay.

Endothelin(s) is (are) generally measured by highly-sensitive RIA (radioimmunoassay) or sandwich-EIA (enzyme immunoassay) methods after preliminary extraction and chromatographic purification using Sep-Pak C18 cartridges; however, there is no general consensus about the range of endothelin circulating levels in healthy subjects and patients. We have evaluated the analytical performance of two commercial RIAs for plasma endothelin-1 assay (supplied by Peninsula Laboratories, Belmont, California, and by Biomedica Gruppe, Biomedica Gesellschaft mbH, Vienna, Austria) in order to verify whether differences in extraction procedures, antibody affinities or standard preparations can explain the different results obtained by these two RIAs. The RIA kits tested in the present study showed some differences in the analytical performance; in particular, different antibody specificities have been observed. The concentration range of endothelin(s) assayed with an imprecision better than 15%, which can be considered the working range, was wider for the Peninsula than for the Biomedica kit (i.e. from 1.6 to 50 fmol/tube vs 0.7 to 10 fmol/tube), whereas the two RIA kits showed similar sensitivity (i.e. about 0.2 fmol/tube). Taking into account the working range and sensitivity of the two RIAs to measure with an acceptable error the samples of normal subjects and the most part of patients, > or = 3-ml volumes of plasma must be extracted by Sep-Pak C18 cartridges and then measured by RIA. Owing to the central role played by the endothelin superfamily in several pathophysiological conditions, it is important to have a reliable assay for the measurement of these peptides in biological fluids and tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗