Molecular analysis of endometrial inflammation in preterm birth.

Spontaneous preterm birth (sPTB) represents the 35%-45% of all preterm birth (PTB) cases and its etiology is unknown. We investigated if the expression level of endometrial cytokines and angiogenetic factors is related to the onset of sPTB.Endometrial tissues from non-pregnant women who experienced sPTB and from non-pregnant women who did not experience sPTB were collected and examined for their expression profile. With this aim, the PCR Array analysis was performed and data were confirmed by Real-Time PCR. Differential gene expression measurements (pathological vs control tissues) showed a significant up-regulation for genes codifying for two angiogenetic factors known as connective tissue growth factor (CTGF), and coagulation factor III (F3). An increased level of expression was detected both for tyrosine kinase endothelial (TEK) and for transforming growth factor beta 2 (TGF-ß2) genes but without reaching the statistical significance. The expression level of interleukin 10 receptor alpha (IL10RA) gene was slightly decreased in pathological group compared to control one but, as well as forTEK and TGF-ß2 measurements, without reaching the statistical significance. Our work is the first to correlate the imbalance in endometrial district of non -pregnant women with sPTB. These data could suggest a new point of view whence to read sPTB. We need additional clinical and biological studies to clarify sPTB pathogenesis.

RET genetic screening of sporadic medullary thyroid cancer (MTC) allows the preclinical diagnosis of unsuspected gene carriers and the identification of a relevant percentage of hidden familial MTC (FMTC).

OBJECTIVE: This study was aimed to demonstrate the clinical benefits of rearranged during transfection (RET) genetic screening in patients with apparently sporadic medullary thyroid cancer (MTC) not only to identify the hereditary nature of the disease in the index case but also to discover family members harbouring the same germline mutations (i.e. gene carriers) who are unaware of their condition. CONTEXT: RET genetic screening allowed the identification of germline RET mutations in apparently sporadic MTC resulting in their re-classification as hereditary forms. PATIENTS AND MEASUREMENTS: RET genetic screening was performed in 729 apparently sporadic MTC patients by direct sequencing RET exons 5, 8, 10, 11 and 13-16. Clinical and biochemical evaluation of gene carriers was also performed. RESULTS: We discovered an unsuspected germline RET mutation in 47 of 729 (6·5%) apparently sporadic MTC who were re-classified as hereditary. We found 60 of 146 (41·1%) gene carriers, 35 of whom had biochemical or clinical evidence of MTC. Thirty gene carriers underwent total thyroidectomy and 27 of 30 (90%) were persistently cured after a mean follow-up of 6·0 years. As a further result of RET genetic screening, we observed a significantly higher prevalence of familial medullary thyroid cancer (FMTC) in our series with respect to the largest series of the International RET Consortium (P = 0·0002). CONCLUSIONS: RET genetic screening of patients with apparently sporadic MTC represents a major tool for the preclinical diagnosis and early treatment of unsuspected affected family members and allows the identification of a relevant percentage of hidden FMTC.

Relationship between maternal hemodynamics and plasma natriuretic peptide concentrations during pregnancy complicated by preeclampsia and fetal growth restriction.

OBJECTIVE: A proper maternal cardiovascular adaptation to the pregnancy plays a key role for promoting an adequate uteroplacental perfusion, for ensuring normal fetal development and for preventing gestational hypertensive complications such as preeclampsia. This study aims to evaluate hemodynamic measurements obtained by noninvasive methods among preclamptic women with and without fetal growth restriction (FGR) and the relationship with plasma levels of natriuretic peptides. STUDY DESIGN: The study compared 98 pregnant women (n=48 with preeclampsia; n=50 normotensive pregnant women) and 50 nonpregnant normotensive control subjects undergoing anultrasonic cardiac output monitor (USCOM) and plasma assessment of atrial N-terminal pro B-type natriuretic peptide (NT-proBNP). The statistical analysis was carried out by analysis of variance and correlation analysis. RESULTS: Preeclampsia state is associated with increased vascular resistance (mean 1587±236 vs 978±153 dyn s cm-3) and lower cardiac output (mean 5.7±1.1 vs 6.78±0.8 l) and this hemodynamic state is associated with higher levels of NT-proBNP (mean 121.2±26.3 vs 42.5±11.4 pg ml-1); furthermore, we found an inverse correlation between maternal cardiac output and plasma levels of NT-proBNP only if preeclampsia is associated with FGR. CONCLUSION: The elevated NT-proBNP in preeclampsia may reflect ventricular stress and subclinical cardiac dysfunction worsening if FGR is present. This may have implications for the acute management of the preeclampsia and FGR women and for appropriately timed therapeutic interventions later in life.

Validation of the Photography Method for Nutritional Intake Assessment in Hospitalized Elderly Subjects.

OBJECTIVE: The aim of the present study was to validate the photographic indirect method as an accurate and specific tool to assess nutritional intake in a cohort of elderly hospitalized patients. DESIGN: this is a prospective observational study. SETTING: hospital (geriatric acute ward and transitional care of IRCCSS AUO San Martino Hospital, Genoa, Italy). PARTICIPANTS: 255 consecutive elderly hospitalized patients. MEASUREMENTS: assessment of malnutrition by: Mini nutritional assessment (MNA) and abbreviated Comprehensive geriatric assessment (CIRS; Barthel index, SPMSE). The direct method (Gold standard): food dish weight (before lunch) and residual (after lunch) food dish weight and estimation of the percentage of eaten food and of residual food for each dish. The percentages of food intake and residual food were calculated according to the following formula: intake %= initial weight of the dishes- residual food weight)/ initial weight dish x100. The unit of variable was the percentage. The indirect photographic method with extrapolation of the lunch food intake by photographic method confronting initial meal and residual meal (25% quartile food dish estimation). RESULTS: The results showed a significant correlation between the direct method (weighing residual food) and the indirect photographic method(n=255; r=0.9735; p<0.001) as well as a significant positive correlation between the indirect photographic method and the food caloric estimation calculated by the direct method (n=255; r= 0.6489, p<0.001). Intraclass coefficient (ICC), showed a highly significant degree of agreement between the gold standard and the indirect photographic method (ICC: 0.69; p<0.0001). Additionally, the results showed a good inter rater agreement of the indirect photographic method (kappa-statistic measure of interrater agreement: (Z=13.04; p<0.001); agreement 70.29% e Kappa=0.5965) and a good specificity of the indirect method as it was independent on the single food item. CONCLUSIONS: The study originally provided the validation of the indirect photographic method for the assessment of nutritional intake in a vast cohort of hospitalized elderly subjects. The present results moved a step forward in the appropriate assessment of nutrition intake in frail elderly, providing an easy to use tool that may be incorporate in routine clinical practice for early and targeted therapeutic interventions.

Acute effects of amiodarone administration on thyroid function in patients with cardiac arrhythmia.

Because little has been published on early effects of treatment with amiodarone on thyroid function, we studied serum total and free thyroid hormone, reverse T3, and TSH levels in patients with cardiac arrhythmias during the first 10 days of treatment with a loading dose of amiodarone by iv infusion. Twenty-four patients were enrolled in the study. A standardized loading regimen for the i.v. infusion of amiodarone was used. The protocol provided the i.v. infusion of 20 mg/kg per day on day 1, the i.v. infusion of 10 mg/kg per day on day 2, then 600 mg/day per os for 7-10 days, and finally, in patients chronically treated with the drug, the dose was gradually reduced to 400-200 mg/day per os. Total and free concentrations of T4 tended to progressively and significantly increase (P < 0.0001 repeated measures ANOVA) starting from the fourth day of therapy, whereas total T3 decreased from the second day progressively (P < 0.0001) throughout the study; free T3 did not significantly change. TSH levels early and significantly (P < 0.001, by ANOVA) increased throughout the study, starting from the first day of therapy and reaching at 10 days a value 2.7 times higher than the basal value. Reverse T3 levels progressively and significantly (after 2 days of treatment) increased and paralleled the TSH values, reaching at the 10th day a value about 2 times higher than basal value. In conclusion, our data suggest that after i.v. treatment with amiodarone: 1) TSH is the first hormone to change significantly followed by reverse T3, T4, and T3; 2) the progressive fall of T3 levels reflects an inhibition of the peripheral conversion of T4 to T3; 3) the observed later increase of total and free T4 levels may be explained by a contribution of direct thyroidal stimulation by TSH and/or by a reduction in T4 clearance.

Evidence that atrial natriuretic peptide tissue extraction is not changed by large increases in its plasma levels induced by pacing in humans.

Atrial natiurectic peptide (ANP) is a cardiac hormone with a very short plasma half-life, which plays an important role in a variety of clinical conditions associated with an increase in pressure and/or volume overload on the heart. The MCR of the hormone is considered to represent a stable parameter, reflecting the uptake and degradation rate of ANP by the periphery, only scarcely affected by rapid oscillations of circulating levels. To evaluate the extent to which MCR is affected by rapid and large variations of circulating levels of the hormone, we measured MCR in five patients with different degrees of myocardial function (from normal to severely impaired), in whom changes in ANP levels were induced by atrial and/or ventricular pacing. Cardiac output was simultaneously measured by thermodilution to calculate whole body extraction of ANP. During constant i.v. infusion of [125I]ANP, the hormone MCR was determined both under basal conditions (at tracer equilibration, 20-30 min after the start of infusion) and during atrial and ventricular pacing. Pacing maneuvers, begun 50 min after the start of infusion, induced a marked and rapid increase in endogenous plasma ANP values in all patients (on the average, 3,7-fold compared to basal values; range, 1.8-5.68), whereas corresponding values of [125I]ANP only minimally changed. The MCR of ANP (3.62 +/- 1.06 L/min, mean +/- SD) slightly decreased (by repeated measures ANOVA, P = 0.0458) during atrial and ventricular pacing procedures (3.35 +/- 1.03 and 3.15 +/- 0.74 L/min, respectively), reaching a mean value of 88.7 +/- 9.0% compared to basal. The small decrease in MCR could be almost completely ascribed to hemodynamic factors; indeed, basal cardiac output (5.76 +/- 1.70 L/min) was found, on the average, to be slightly decreased during atrial and ventricular pacing (5.28 +/- 1.46 and 5.16 +/- 1.33 L/min, respectively), and so whole body extraction of the hormone, measured before pacing (50.0 +/- 12%), remains stable throughout the study period (50.4 +/- 10.6% and 49.6 +/- 10% during atrial and ventricular pacing, respectively). Our findings demonstrate that degradative mechanisms involved in ANP clearance are not saturable at least for acute elevations of ANP plasma levels up to 3-5 times the basal level.

Distribution and subcellular localization of acylpeptide hydrolase and acylase I along the hog gastro-intestinal tract.

The distribution of acylase I and acylpeptide hydrolase along the hog small intestine was investigated. No significant changes in their respective specific activity was found when the intestine was cut off and divided into eight segments (taken every 200 cm) so as to specifically study the duodenum, jejunum and ileum. Upon performing subcellular fractionation of hog enterocytes, it was observed that acylpeptide hydrolase is a soluble enzyme, while acylase I is essentially a soluble protein accounting for only 5% of the activity associated with the whole membrane fraction. The membrane-bound acylase I was neither solubilized by phosphatidylinositol-specific phospholipase C from Bacillus cereus nor by detergents which are commonly used to solubilize alkaline phosphatase, a glycosylphosphatidylinositol-anchored protein. When a phase separation was carried out in Triton X-114, all the anchored-membrane proteins of the intestinal membranes were located in the detergent-rich phase, while acylase I was present in the detergent-poor phase. Finally, the immunolabeling of intestinal cells with specific antibodies definitively established the cytoplasmic localization of acylase I. Acylpeptide hydrolase and acylase I therefore both are located in the enterocyte cytoplasm.

The hog intestinal mucosa acylase I: subcellular localization, isolation, kinetic studies and biological function.

The soluble acylase I (N-acylamino acid amidohydrolase, EC 3.5.1.14) from hog intestinal mucosa was 11,000-fold purified for the first time using a new four-step procedure involving an immunoaffinity chromatography. The resulting protein, which had an isoelectric point of 5.2 and a M(r) of 90,000 was composed of two apparently identical N-acylated polypeptide chains. Its amino acid composition was comparable to that of hog kidney acylase I. The enzyme had a pH optimum at 8.0 and required Zn2+ or Co2+. The optimal temperature for the acylase reaction was 40 degrees C and the activation energy of thermodenaturation was estimated at 260 kJ mol-1. The enzyme was strongly inhibited when preincubated with chelating agents, by diethyl pyrocarbonate under histidine-modifying conditions as well as by sulfhydryl compounds. The reaction of the purified enzyme with the synthetic substrate furylacryloyl-L-methionine was partly characterized as follows: Km = 0.22 +/- 0.03 mM, kcat = 128.0 +/- 17.8 s-1 and kcat/Km = 5.8 +/- 1.6 x 10(5) M-1 s-1. The L-stereoisomer of methionine competitively inhibited the enzyme reaction with a Ki of 3.4 +/- 0.2 mM. It is suggested that acylase I might not only be involved in the catabolism of intracellular N-acylated protein but also be responsible for the biological utilization of N-acylated food proteins.

In vitro oxidative decarboxylation of L-2-hydroxy-4-methylthiobutanoic acid by L-2-hydroxy acid oxidase A from chicken liver.

The first step in the set of reactions responsible for the biological utilization of L-2-hydroxy-4-methylthiobutanoic acid, the methionine hydroxy analogue, in protein synthesis was investigated in vitro using pure L-2-hydroxy acid oxidase A from chicken liver. The reaction yielded no more than 20% of the corresponding alpha-keto acid, the well-known intermediate in methionine metabolism, and as much as 80% of the subsequent decarboxylation product, 3-methylthiopropionate, suggesting that L-2-hydroxy-4-methylthiobutanoic acid cannot be completely converted into methionine in vivo. It was therefore concluded that chicken liver L-2-hydroxy acid oxidase, a peroxisomal enzyme requiring flavin mononucleotide as a coenzyme, also has an oxidative decarboxylation activity in vitro, which was found to be NADH-dependent. The mechanism possibly underlying the successive conversion of the methionine hydroxy analogue into alpha-keto acid and 3-methylthiopropionate by this NADH:flavin oxidoreductase-decarboxylase activity is described.

Inhibitory effects of anions and active site amino acid sequence of chicken liver L-2-hydroxyacid oxidase A, a member of the FMN-dependent alpha-hydroxyacid oxidizing enzyme family.

Monocarboxylic acids with aliphatic chains were found to be mixed inhibitors of chicken liver L-2-hydroxyacid oxidase A when L-2-hydroxy-4-methylthiobutanoic acid was used as the substrate. The finding that the binding affinity of the enzyme for monocarboxylic acids was directly proportional to the number of carbon atoms in the chain strongly suggests that in addition to the electrostatic interaction due to the carboxyl moiety, hydrophobic forces may also be involved in the binding affinity of monocarboxylic acids to the enzyme's active site. Oxalate, a dicarboxylic acid, also resulted in a mixed-type inhibition of chicken liver L-2-hydroxyacid oxidase A, and, surprisingly, its binding affinity to the enzyme was found to be quite high as compared with monocarboxylic acids. This is probably due to the fact that the two carboxyl groups of oxalate give rise to electrostatic interactions with the positively charged side chains of two adjacent residues in the polypeptide chain. The inhibitory effects of other dicarboxylic acids was found to decrease as the number of carbon atoms in the chain increased. Oxamate was found however to be a novel type of potent inhibitor of the enzyme. All in all, these kinetic studies and the amino acid sequence determination in the active site region after limited proteolysis of the polypeptide chain definitely establish that chicken liver NADH/FMN containing L-2-hydroxyacid oxidase A is a member of the FMN-dependent alpha-hydroxyacid oxidizing enzyme family.

Findings from long-term electrocardiographic monitoring of patients with variant angina in a coronary care unit.

Eleven patients with frequent episodes of variant angina underwent 24-hour electrocardiographic monitoring in a coronary care unit for a total of 70 days to assess circadian variation in ischemic episodes and its correlation with circadian heart rate (HR) rhythm. In each patient a series of 4 to 13 consecutive days, in the absence of therapy, with 8 or more ischemic episodes per day were analyzed. Harmonic regression models were fitted to the hourly number of ischemic episodes and the hourly values of HR. Out of 54 days, with 8 or more episodes per day for a total of 1,357 episodes, a circadian rhythm was observed for 34 days (64%), in at least 1 day in all patients and during the entire period of observation in only 3. Its presence was independent of the number of episodes; the peak of periodic functions occurred at 2.9 +/- 2.7 AM. A cadian rhythm for HR was observed in 61 of the 70 days (87%), consistently in 7 patients; the nadir occurred at 2.4 +/- 1.5 AM; simultaneous cycling in HR and transient ischemia was found on 32 days. The intrapatient difference between the peak and the nadir of the ischemic and the HR function was, on average, 2.6 +/- 3.3 hours. Thus, a circadian rhythm of ischemic episodes was present in all patients although it was not consistently present; simultaneous occurrence of circadian variation in ischemic episodes and HR was observed only in 60% of the days with a sufficiently high number of attacks and when this occurred, a significant phase shift was observed; occasional loss of HR cycling was observed in some patients, without an apparent cause.

Ventricular arrhythmias in dilated cardiomyopathy as an independent prognostic hallmark. Italian Multicenter Cardiomyopathy Study (SPIC) Group.

Prevalence and characteristics of ventricular arrhythmias (VA) on Holter monitoring were evaluated in 218 patients with invasively documented idiopathic dilated cardiomyopathy to clarify their relation to pump dysfunction, and their prognostic role. VA were observed in 205 patients (94%) and were high grade (ventricular pairs or tachycardia) in 130 (60%). No simple or multiform ventricular premature complexes were present in 88 patients (group 1; 41%), ventricular pairs in 63 (group 2; 32%), and ventricular tachycardia in 67 (group 3; 27%). Only echocardiographic right ventricular dimensions (p less than 0.05) and prevalence of VA during effort (8% in group 1, 15% in group 2, and 14% in group 3; p = 0.0005) differed significantly between groups. VA severity, and number of ventricular premature beats and tachycardia episodes were not correlated to right/left ventricular dimensions and pump function indexes. During a mean follow-up of 29 +/- 16 months, 27 patients died from cardiac events, and 16 received transplants. Three-year survival probability was lower in groups 2 (0.82) and 3 (0.81) than in group 1 (0.94). By Cox multivariate analysis, VA severity (p less than 0.01) was a major independent predictor of prognosis after markers of ventricular dysfunction such as left ventricular ejection fraction (p less than 0.001) and stroke work index (p less than 0.001).

Effect of coronary bypass and cardiac valve surgery on systemic endothelial function.

Seventeen patients scheduled for a cardiac procedure necessitating cardiopulmonary bypass underwent serial perioperative assessment of brachial artery flow-mediated dilation. Patients who underwent coronary bypass surgery had a sustained systemic endothelial dysfunction in the perioperative period, whereas those undergoing cardiac valve surgery experienced transient postoperative systemic endothelial dysfunction.

Comparison of verapamil and propranolol therapy for angina pectoris at rest: a randomized, multiple-crossover, controlled trial in the coronary care unit.

The effects of oral verapamil (V), 400 mg/day, oral propranolol (P), 300 mg/day, and placebo were compared in 10 patients admitted to the coronary care unit because of frequent attacks of angina at rest. Testing was done according to a randomized, double-blind, multiple-crossover, placebo-controlled trial, consisting of 8 consecutive 48-hour treatment periods with V or P or placebo. Three patients had variant angina, 5 had episodes of both ST-segment elevation and depression and 2 had only ST-segment depression. One patient had no critical coronary stenoses, 1 had 1-vessel disease, 7 had 2-vessel disease and 1 had 3-vessel disease. Electrocardiographic monitoring and tape recording were continued during the 16 days of the trial. A total of 1,602 episodes of transient diagnostic ST shift were recorded during the trial (1,309 episodes of ST-segment elevation, 293 of ST-segment depression); 43% were painless. Mean blood levels of V and P at the end of the active phases were 161 +/- 89 and 120 +/- 45 ng/ml, respectively. In the group as a whole, the average number of diagnostic ischemic ST-segment shifts per 24 hours was significantly reduced relative to corresponding placebo periods during V (2.6 +/- 2.4 vs 11.9 +/- 8.6; p less than 0.01) but not during P treatment (11.9 +/- 8.6 vs 12.0 +/- 7.3). Similar statistically significant reductions were observed in the number of anginal attacks and nitroglycerin tablets consumed. Considering individual patients, V reduced ischemic episodes during both active phases in all patients, whereas P was effective only in 1.(ABSTRACT TRUNCATED AT 250 WORDS)

HLA segregation of human T-cell subpopulation markers.

Antisera recognizing subsets of human T lymphocytes can be produced by planned immunizations involving HLA-A and HLA-B compatible donors. The reactivity of these antisera against some individuals of a population, but not others, show that they recognize a polymorphic cell surface component. The study of informative families shows the HLA linkage of at least some of these alloantigenic determinants.

Role of dipyridamole-echocardiography test in the evaluation of coronary reserve after coronary artery bypass grafting.

The object of this study was to assess the usefulness of the dipyridamole-echocardiography test in the early evaluation of coronary artery bypass grafting, when the use of an exercise stress test is precluded. We studied 39 consecutive patients (37 men and two women, mean age 57.3 years) referred to our institute for elective coronary artery bypass. Five patients had single, 12 patients double, 20 patients triple vessel disease, and two had left main stem disease. Nineteen left internal mammary artery grafts, 20 sequential grafts, and 39 single vein grafts were performed. All the patients were subjected to the test before (time range 1 to 3 days) and after (time range 6 to 10 days) the operation in the absence of therapy. Dipyridamole was administered intravenously 0.56 mg/kg over 4 minutes (low dose); if no effect was apparent, an additional 0.28 mg/kg over 2 minutes (high dose) was given. During the test, blood pressure and a twelve-lead electrocardiogram were monitored. An arbitrary wall motion score was derived by dividing the left ventricle into six regions and grading from 0 to 3-normokinetic, hypokinetic, akinetic, and dyskinetic zones. Preoperatively the test was positive in 38 patients as evidenced by wall motion abnormalities (36 patients had electrocardiographic changes) and in one patient by electrocardiographic changes and chest pain; 22 tests were positive after the low dose and 17 after the high dose. Angina was present in 33 patients. Mean wall motion score was 1.64 per patient in the basal condition and 4.03 per patient after the test (p less than 0.001). After coronary bypass in three patients the test was positive at the same dosage that was used preoperatively, as shown by wall motion abnormalities (in two patients by electrocardiographic changes, as well). Four patients had symptoms. Furthermore, at 6 months' follow-up, a treadmill stress test performed in these three patients was positive for ischemia and angina. The wall motion score was 1.25 per patient in the basal condition and 1.53 per patient after the test (no significant difference). When the preoperative wall motion score obtained after dipyridamole echocardiography was compared with the postoperative score, a statistically significant difference was seen: 4.03 per patient versus 1.53 per patient (p less than 001). In eight patients we observed an improvement of basal myocardial contractility after the operation, which indicates the reversibility of wall motion abnormalities observed before coronary bypass. In conclusion our data show that the dipyridamole-echocardiography test is a suitable method for the early assessment of bypass grafting when other methods, exercise dependent, are not indicated.(ABSTRACT TRUNCATED AT 400 WORDS)

Up-regulation of 'clearance' receptors in patients with chronic heart failure: a possible explanation for the resistance to biological effects of cardiac natriuretic hormones.

BACKGROUND: Three specific receptors for the cardiac natriuretic peptide system have been identified to date. Down-regulation of the biologically active binding sites (i.e. NPR-A and NPR-B) could explain the blunted response to cardiac natriuretic hormones observed in heart failure (HF), but not the increased metabolic clearance rate. Variations in the ratio between biological and clearance (NPR-C) receptors in target tissue may explain this increase. AIM: The aim of this study was to investigate the regulation of NPR-C receptors on platelets, in patients with HF. METHODS: Eighteen patients with HF (NYHA class: I-II, n=8; III-IV, n=10) and 18 age-matched healthy subjects were studied. The affinity constant (K(d)) and density (B(max)) of binding sites were derived by saturation assays on platelet suspensions using 125I-ANP as radioligand. RESULTS: B(max) increased as a function of the severity of disease: 21.3+/-3.3 fmol/10(9) cells in class III-IV, 11.7+/-2.2 in class I-II, and 11.6+/-1.1 in controls, respectively (P=0.0179 for class III-IV vs. controls and P=0.0451 vs. NYHA I-II). CONCLUSIONS: The increase in density of 'clearance' receptors in severe HF is theoretically consistent with the reduction in cardiac natriuretic peptide biological activity, as well as the increase in metabolic clearance rate. This suggests that clearance receptor blockade may be of potential therapeutic value in HF.

Thyroid hormones homeostasis in pediatric patients during and after cardiopulmonary bypass.

The concentrations of thyroid hormones were measured in 14 pediatric patients before, during, and after cardiopulmonary bypass. The ages of the patients ranged between 18 months and 14 years. Patients were kept normothermic, or moderate or deep hypothermia was induced depending on the specific pathologic condition involved. A marked reduction in the levels of total triiodothyronine, total thyroxine, free triiodothyronine, and thyroid-stimulating hormone, and in the ratio of free triiodothyronine to free thyroxine was detected during the time frame of the study. The minimum levels of each hormone were reached between 12 and 48 hours after cardiopulmonary bypass, indicating that changes in thyroid function and in the conversion of thyroxine to triiodothyronine are triggered by cardiopulmonary bypass and represent specific phenomena, and that these changes are progressively exacerbated during the post-operative period. The thyroid-stimulating hormone level was markedly reduced versus its baseline values (24% +/- 0.13%), despite low levels of both total (40% +/- 18%) and free (39% +/- 20%) triiodothyronine: it returned to its preoperative level by the third postoperative day, but both the total (75% +/- 10%) and free (74% +/- 3%) triiodothyronine levels remained below their baseline values for 7 days postoperatively. Neither hemodilution nor hypothermia was responsible for the alteration observed. We conclude that pediatric patients undergoing cardiopulmonary bypass manifest changes in hormone metabolism similar to those seen in adult patients. These changes increase progressively during the postoperative period, and are still present 7 days postoperatively. The exact mechanism responsible for causing these changes is not thoroughly understood. Whether triiodothyronine replacement therapy is beneficial or deleterious remains controversial.

Preoperative assessment of coronary artery disease in aortic stenosis: a dipyridamole echocardiographic study.

BACKGROUND: The aim of this study was to establish the feasibility, safety, and diagnostic accuracy of the dipyridamole echocardiography test in patients with severe aortic valve stenosis for noninvasive detection of coexisting coronary artery disease. METHODS: The high-dose dipyridamole echocardiography test was performed in 52 patients with severe aortic stenosis; all patients also underwent coronary angiography, independent of test results, before cardiac operation. RESULTS: The dipyridamole echocardiography test was completed without major complications. One patient had transient atrial fibrillation that was reversed by aminophylline. Thirty-one patients (60%) had a negative test result; all had normal coronary arteries. Ten of the 21 patients (48%) with a positive test result had coexisting coronary artery disease. The positive predictive value of the dipyridamole echocardiography test for detection of coronary disease in patients with severe aortic stenosis was 48%. The negative predictive value was 100%. The sensitivity was 100% and the specificity was 74%. CONCLUSIONS: Dipyridamole echocardiography is a safe and feasible tool in patients with severe aortic stenosis eligible for a cardiac operation. A negative test result reliably rules out a significant stenosis, whereas a positive one is much less accurate in predicting coronary artery disease.