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F Santini

Publications and source records attributed to F Santini.

At least 109 records · Page 6Linked to original sources

A study of the serum 3,5,3'-triiodothyronine sulfate concentration in normal and hypothyroid fetuses at various gestational stages.

We have studied T3 sulfate (T3S) levels, blindly, in coded plasma samples from 21 normal and 3 hypothyroid fetuses at different stages of gestation (19-42 weeks). Fetal plasma samples were obtained by cordocentesis. T3S was detectable in all samples studied, with values ranging from 50-294 (mean +/- SD, 130 +/- 62 pmol/L). Plasma T3S was low (< 45 pmol/L) in all 4 normal adult control subjects studied simultaneously; serum T3S ranged from less than 20 to 130 in another set of 18 control subjects (mean +/- SD, 63 +/- 32 pmol/L). Fetal T3S values were positively correlated with gestational age (r = 0.43; P < 0.05), but not with free T4 (FT4), FT3, or TSH values. In the 3 hypothyroid fetuses at 31, 38, and 40 weeks gestation, respectively, plasma TSH was elevated (26, 98, and 24 mU/L, respectively), FT4 was low (10, 6.7, and 7.5 pmol/L, respectively), and FT3 was normal or high (3.2, 8.2, and 2.2 pmol/L, respectively). However, T3S values in hypothyroid fetuses (88, 133, and 252 pmol/L, respectively) were similar to those in normal fetuses at corresponding gestational ages. We conclude that 1) T3S is detectable in fetal circulation from at least 19 weeks gestation, and its concentration increases with fetal-age; 2) plasma T3S concentrations in the fetus at 19-40 weeks gestation are at least comparable to but generally higher than those in the adult; and 3) plasma T3S levels in hypothyroid fetuses are similar to those in normal fetuses. Recent studies demonstrating the ability of some fetal rat tissues (e.g. cerebral cortex) to desulfate T3S to T3 have suggested a possible role of T3S as a source of T3. Normal T3S in fetal hypothyroidism suggests that T3S may contribute to attenuation of the effects of hypothyroidism during intrauterine life.

Embryonic and Fetal Development↗

Antibodies producing complement-mediated thyroid cytotoxicity in patients with atrophic or goitrous autoimmune thyroiditis.

Thyroid-cytotoxic antibodies (thyroid-cytotoxic Abs) have been described in patients with autoimmune thyroiditis, but their role in the development of hypothyroidism remains to be clarified. In this study, we evaluated the pathogenetic role of thyroid-cytotoxic Abs in 20 patients with atrophic thyroiditis (idiopathic myxedema; AT) and 94 patients with goitrous Hashimoto's thyroiditis (HT). Among patients with HT, 27 were euthyroid (HT-E), 27 had subclinical hypothyroidism (HT-SH), and 40 had overt hypothyroidism (HT-H). Seventeen normal subjects and 8 patients with nonthyroidal illnesses were used as controls (C). To detect thyroid-cytotoxic Abs, human thyroid cells expressing thyroid peroxidase (TPO) were labeled with 51Cr and challenged with the immunoglobulin G (IgG) fraction of serum plus rabbit complement. The cytotoxic effect of IgGs was calculated as the percent specific lysis (% SL), taking into account the lytic effect of complement alone and the maximal lysis produced by a detergent. Most C-IgGs decreased the cytotoxic effect of complement (median % SL, -3.3). IgGs from hypothyroid patients with thyroiditis had a greater cytotoxic effect than C-IgGs, either as a whole group (P < 0.001), or when subdivided according to clinical diagnosis: HT-SH (median % SL, 4.8; P < 0.005), HT-H (%SL, 2.2; P < 0.0001), or AT (%SL, 0.9; P < 0.01). Among patients with HT, the lytic activity of IgGs from patients with subclinical and overt hypothyroidism was higher than that of IgGs from euthyroid patients (P < 0.05). The results of IgGs from euthyroid patients with HT (median % SL, -0.9) did not significantly differ from those of C-IgGs. By taking a cut-off over the upper range of % SL produced by C-IgGs (> 2), the prevalence of thyroid-cytotoxic Abs was 30% in AT, 59% in HT-SH, and 55% in HT-H. However, 37% of euthyroid patients with HT also had thyroid-cytotoxic Abs. No IgG containing TPO antibodies (TPOAb) at low titer (< 40(2)) was cytotoxic. However, the levels of thyroid-cytotoxic Abs did not correlate with TPOAb titers, and preabsorption with TPO only partially abolished the lytic effect of some HT-IgG. These findings suggest that TPO is a target of thyroid-cytotoxic Abs, but other thyroid antigens are also involved in the cytotoxic reaction.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Pulmonary atresia, intact ventricular septum, and Ebstein anomaly of the tricuspid valve. Anatomic and surgical considerations.

Pulmonary atresia with intact ventricular septum is a disorder that involves the whole right ventricle. An associated Ebstein deformity of the tricuspid valve is found in 10% of the cases, further complicating the anatomy and the function of the right ventricle. From January 1966 to December 1990, pulmonary atresia, intact ventricular septum, and Ebstein deformity of the tricuspid valve were observed in 11 cases in our institution; four of them were necropsy findings and the remaining seven were patients treated surgically. Of the latter, two were boys and five were girls (age range 1 day to 18 days). Two patients were managed by pulmonary valvotomy, three by systemic-pulmonary artery shunt, and two had a combination of the two. Operative mortality was 57%. Eight hearts were available for morphologic study. All had viscero-atrial situs solitus, D-loop ventricular structure, and normally related great arteries. A correlation between the degree of tricuspid valve dysplasia and right ventricular cavity size was observed in all. Furthermore, in five cases the anterior leaflet of the tricuspid valve obstructed the right ventricle at the ostium infundibuli level. In two of our surgical patients, a protruding anterior tricuspid valve leaflet was identified and excised and both patients survived. Ebstein anomaly of the tricuspid valve further complicates surgical management and outcome of pulmonary atresia and intact ventricular septum. Potential obstruction at the ostium infundibuli level should always be considered during repair. Various degrees of right ventricular inlet dysplasia, always present in this complex, may contraindicate an anatomic correction. In these cases a modified Fontan-type procedure should be considered as a valid surgical option.

Abnormalities, Multiple↗

Metabolism of 3,5,3'-triiodothyronine sulfate by tissues of the fetal rat: a consideration of the role of desulfation of 3,5,3'-triiodothyronine sulfate as a source of T3.

We have recently demonstrated that serum concentration of 3,5,3'-triiodothyronine sulfate (T3S) is markedly elevated in the human newborn at a time when serum 3,5,3'-triiodothyronine (T3) is very low. The present study explores the ability of maternal (19-21 d pregnant) and near-term fetal Sprague-Dawley rat tissues to 1) monodeiodinate T3S and T3 in both the outer and the inner ring and 2) desulfate T3S to T3. Maternal liver microsomes metabolized T3S exceedingly efficiently (compare fetus p less than 0.05). Eighty percent or more of T3S was consumed during its incubation with 360 micrograms/mL microsomes for 2 h. The majority of the consumption of T3S by adult liver microsomes occurred by its 5'-monodeiodination to I-; little inner-ring monodeiodination to 3,3'-diiodothyronine was demonstrable. In fetal liver microsomes, however, over 75% of the substrate T3S remained unchanged after a 2-h incubation. T3 was metabolized similarly moderately by fetal and maternal liver microsomes. Brain microsomes metabolized T3S poorly in both the mother and the fetus. Over 90% of substrate T3S remained unchanged after a 2-h incubation in each case. Interestingly, brain microsomes metabolized T3 more rapidly than T3S (p less than 0.05). In the fetus, desulfation of T3S to T3 was clearly evident only in microsomes from the liver and the brain; in the adult, it was plentiful in many tissues. Fetal liver and brain tissues metabolize T3S poorly, and both actively desulfate T3S to T3. These data and those indicating high serum T3S in the fetus suggest that T3S is a local source of T3 in critical tissues in the fetus and possibly in adults with the low T3 syndrome.

Animals↗

A study of the characteristics of the rat placental iodothyronine 5-monodeiodinase: evidence that it is distinct from the rat hepatic iodothyronine 5'-monodeiodinase.

Recent studies have demonstrated that rat liver type I iodothyronine 5'-monodeiodinase (5'-MD) characteristically contains selenocysteine. The present study was undertaken to characterize rat placental type III iodothyronine 5-MD and to compare it with 5'-MD. Solubilized rat placental microsomes were delipidated by carboxymethyl cellulose-Sephadex chromatography. Phospholipids and proteins were recovered in two distinct peaks, which did not show 5-MD activity. 5-MD activity was recovered fully, however, by combining the two components (phospholipids and protein) and partially after the addition of exogenous phospholipids to protein. Tissue selenoproteins were labeled by injection of radioactive selenium (75Se; 50 microCi, iv; on days 5, 10, and 15 of gestation) to pregnant rats. Subcellular fractions of maternal and fetal tissues were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by autoradiography. No specific seleno-labeled proteins were evident in the microsomes of placenta or maternal or fetal brain. A 27- to 29-kilodalton (kDa) band previously suggested to be 5'-MD was observed, however, in maternal liver and kidney microsomes. Aurothioglucose inhibited rat placental 5-MD, but the dose required for 50% inhibition was over 50-fold greater than that for Se-containing hepatic 5'-MD (430 vs. 8 nM). The mechanism of the inhibition was noncompetitive for 5-MD, whereas it was competitive for 5'-MD. A synthetic peptide of 16 amino acids corresponding to the carboxy-terminal portion of 5'-MD was synthesized, and rabbits were immunized with the peptide-BSA conjugate. Western blots studies using the rabbit antiserum showed one specific 29-kDa band in rat liver microsomes. However, no specific bands were observed in 5-MD-rich placental or fetal brain microsomes. Bromoacetyl T3 (BrAcT3) was a potent inhibitor of rat placental 5-MD. Affinity labeling of solubilized rat placental microsomes with [125I]BrAcT3 showed a predominant band of 31 kDa, distinct from the 27- to 29-kDa band found in liver and kidney. The labeling of the 31-kDa band was enhanced by 10 mM dithiothreitol, inhibited 60% by 150 microM T3, and prevented by 40 microM aurothioglucose. A dominant affinity-labeled 31-kDa band was also observed in fetal brain microsomes. Some tissues without 5-MD activity (testes and spleen) also showed weak binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A study of the characteristics of hepatic iodothyronine 5'-monodeiodinase in various vertebrate species.

Rat type I iodothyronine 5'-monodeiodinase (5'-MD) has recently been shown to be a selenium-containing enzyme. In the present study we compared the characteristics of the 5'-MD from liver microsomes of rat, mouse, guinea pig, man, beef, pig, sheep, and chicken. Aurothioglucose (ATG), a known potent inhibitor of selenium-containing enzymes, was a consistent, very potent inhibitor of 5'-MD activity in all species studied, with a 50% inhibitory dose in the narrow range of 5.8-12 nM. ATG was also a potent and selective inhibitor of [125I]bromoacetyl T3 affinity labeling of 5'-MD. Thus, in the species studied, only one affinity-labeled band, which was selectively displaced by gold, was identified. The mol wt of the affinity-labeled proteins in various liver microsomal preparations ranged between 28-36 kilodaltons (kDa), and the ATG concentrations necessary for the inhibition of affinity labeling of microsomes with [125I]bromoacetyl T3 were comparable to those required for inhibition of the enzyme activity in all species except the pig. The pig liver microsomes demonstrated a dominant affinity-labeled 36-kDa band, but much higher ATG concentrations (micromolar) were required for inhibition of affinity labeling. In view of the potent inhibition of pig liver 5'-MD activity by ATG, it appears unlikely that this band in the pig corresponds only to the substrate-binding site of 5'-MD, but this issue requires further study. A synthetic peptide of 16 amino acids corresponding to the carboxy-terminal portion of rat 5'-MD was synthesized, and rabbits were immunized with the peptide-BSA conjugate. Western blot studies using the rabbit antiserum showed one specific 29-kDa band in rat liver and kidney microsomes and thyroid homogenate. No specific bands were observed in other adult rat tissues studied or in fetal rat liver. No specific bands were observed when Western blot studies with antibody against the carboxy-terminal portion of rat 5'-MD were performed in liver microsomes from species other than the rat. In conclusion, our studies indicate that selenium is a likely component of type I 5'-MD in all species studied. However, substantial structural differences exist between the rat type I 5'-MD and that in various other species.

Affinity Labels↗

A study of metabolism of deaminated and sulfoconjugated iodothyronines by rat placental iodothyronine 5-monodeiodinase.

The interaction of the rat placental type III iodothyronine 5-monodeiodinase (5-MD) with acetic acid (AA), propionic acid (PA), and sulfoconjugate (SA) derivatives of thyroid hormones has been investigated in comparison with hepatic iodothyronine type I MD. PA and AA derivatives of both T3 and T4 were potent inhibitors of 5-monodeiodination of [125I]T3 by rat placental microsomes. 3,5,3'-Triiodothyroacetic acid (T3AA) and 3,5,3'-triiodothyropropionic acid (T3PA) were comparable to T3 in their ability to inhibit 5-monodeiodination of [125I]T3, whereas T4AA and T4PA were more potent than T4. 3,5,3'-triiodothyrosulfonic acid (T3SA), T4SA, and rT3SA caused little or no inhibition of placental 5-MD activity. Among various analogs of T3 or T4, the order of relative potency of inhibition of hepatic 5'-MD was PA > AA > SA > parent iodothyronine. The metabolism of T3 and its derivatives by rat placental microsomes was studied by determining the rates of disappearance of the various substrates and the production of the metabolites generated by inner ring monodeiodination of the substrate. T3AA and T3PA were metabolized at a rate comparable to that of T3. Under the same conditions, essentially 100% of T3SA remained intact. Kinetic studies of placental inner ring monodeiodination of T3, T3AA, and T3PA demonstrated comparable values for Km (1.3, 1.8, and 2.3 nM, respectively) and maximum velocity (44, 57, and 74 fmol/micrograms.h, respectively). All derivatives of T3 studied were deiodinated by hepatic type I MD more avidly than the parent iodothyronine. Our data suggest that 1) deamination does not appreciably influence, while sulfoconjugation markedly inhibits type III 5-monodeiodination of T3; and 2) deamination may be even more conducive to degradation of thyroid hormone than sulfoconjugation.

Animals↗

A radioimmunoassay of rat type I iodothyronine 5'-monodeiodinase.

A highly sensitive, specific, and reproducible RIA has been developed to measure rat type I iodothyronine 5'-monodeiodinase (5'-MD). A 16-amino acid peptide (LAP-744) corresponding to a portion of the carboxy-terminal region of the rat liver 5'-MD, as predicted from its cDNA, was synthesized, and rabbits were immunized with the peptide-BSA conjugate. In a final dilution of 1:15,000, our anti-5'-MD antibody bound about 30-35% of a tracer amount of [125I]LAP-744. The detection threshold of the RIA approximated 0.08 pmol LAP-744 or an equivalent amount of 0.08 pmol 5'-MD. Rat liver and kidney microsomes produced dose-response curves that were essentially parallel to that of LAP-744. No inhibition of binding of [125I]LAP-744 to antibody was produced by 0.3 mg or less rat microsomal proteins from testes, heart, brain, muscle, spleen, intestine, lung, placenta, or fetal liver. Recovery of nonradioactive LAP-744 added to spleen microsomes averaged 103%. The coefficient of variation averaged 4% within an assay and 11% between assays. In 16 normal rats studied, the mean (+/- SD) 5'-MD content was 2.4 +/- 0.22 pmol/mg protein in liver microsomes and 2.5 +/- 0.27 pmol/mg protein in kidney microsomes. Fasting of the rat for 2-4 days was associated with a significant reduction in both the activity and the content of the 5'-MD in liver and kidney. Hypothyroidism was also associated with a significant decrease in the activity and content of 5'-MD in both tissues. Significant opposite changes were observed in these parameters in hyperthyroidism. Treatment of the rat with sodium ipodate for 3 days was associated with a significant decrease in both the activity and the content of 5'-MD in liver and kidney. A similar treatment of the rat with propylthiouracil induced a clear reduction in the activity of 5'-MD in liver and kidney, but the content of the enzyme was significantly increased in both tissues. Rats treated with aurothioglucose for 3 days exhibited a significant decrease in 5'-MD activity in liver and kidney microsomes, whereas the tissue content of 5'-MD was not affected. A similar treatment of the rat with methimazole had no significant effect on either the activity or the content of 5'-MD.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Evidence that the human placental 5-monodeiodinase is a phospholipid-requiring enzyme.

Gel filtration (GFI) of the solubilized human placental microsomes (SHPMP) performed in an Ultrogel AcA-34 column in the presence of 1 mM 3-(3-cholamidopropyl)dimethylammonio-1-propane sulfonate (CHAPS) plus 10 mM n-octyl-beta-D-glucopyranoside (beta-OG) demonstrated two main protein peaks. The 5-Monodeiodinase (5-MD) activity measured by the conversion of [125I]T3 to [125I]3,3'-diiodothyronine in a 2- to 18-h incubation at 37 C in the presence of 10 mM dithiothreitol was detected only in the first peak, and the specific activity was increased about 9 times over that of the starting SHPM. The fractions containing most of the 5-MD activity were filtered through a second Ultrogel AcA34 column (GFII) in the presence of 2 mM CHAPS plus 20 mM beta-OG. In these conditions, 5-MD activity was detected in low amounts only in the second peak. Cation exchange chromatography on carboxymethylcellulose-Sephadex with a starting buffer of pH 5 containing 2 mM CHAPS plus 20 mM beta-OG, followed by a pH 8 buffer, showed a very small OD peak at the void volume (P) and a second peak with about 95% of the protein (E). However, no 5-MD activity was detectable in either peak, while a nearly complete restoration of the enzyme was achieved when P and E were mixed. 5-MD was also completely restored by combination of P with the first inactive peak of GFII. When P was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, no distinct protein bands were observed. After ethanol-ether extraction and digestion with H2SO4 and H2O2, inorganic phosphate was detectable only in P, suggesting the presence of phospholipids. We next studied the effect of phosphatidyl serine (PS), phosphatidyl choline (PC), or phosphatidyl ethanolamine (PE) on 5-MD activity of E (5 micrograms protein/mL). The 5-MD activity was recovered in a dose-response manner with all phospholipids studied, but PS was the most effective agent for reconstitution. At 1 microgram/mL, 5-MD activity, expressed as a percentage of the total P plus E activity, was 101% for PS, 35% for PC, and 20% for PE. The addition of rat liver or kidney microsomes (80 micrograms/mL) to E (5 micrograms/mL) provided recoveries of 79% and 48%, respectively, of the total P plus E activity. The following conclusions were reached. 1) Phospholipids are essential for the 5-MD activity of SHPMP. 2) CHAPS and beta-OG may extract phospholipids from the membranes without denaturation of the 5-MD.(ABSTRACT TRUNCATED AT 400 WORDS)

Cholic Acids↗

A radioimmunoassay for measurement of 3,5,3'-triiodothyronine sulfate: studies in thyroidal and nonthyroidal diseases, pregnancy, and neonatal life.

A highly sensitive, specific, and reproducible RIA has been developed to measure T3 sulfate (T3S). Only T4 sulfate cross-reacted significantly (approximately 3%) in the RIA; rT3 sulfate, T4, T3, rT3, and diiodothyronine cross-reacted less than 0.01%. T3S was bound by thyronine-binding globulin and albumin in serum. The free fraction of T3S in four normal sera averaged 0.25% compared to a value of 0.35% for T3. Therefore, T3S was measured in ethanol extracts of serum. Recovery of the nonradioactive T3S added to serum averaged 92%. The dose-response curves of inhibition of binding of [125I]T3S to anti-T3S antibody by serial dilutions of serum extracts were essentially parallel to the standard curve. The detection threshold of the RIA was 20 pmol/L (1.5 ng/dL). The coefficient of variation averaged 7.8% within an assay and 11% between assays. The serum concentration of T3S was (mean +/- SE) 76 +/- 7.2 pmol/L in normal subjects, 268 +/- 29 in hyperthyroid patients with Graves' disease, 92 +/- 28 in hypothyroid patients, 201 +/- 32 in patients with systemic nonthyroidal illnesses, 40 +/- 6.2 in pregnant women (15-31 weeks gestation), and 429 +/- 39 in cord sera of newborns; the values in hyperthyroidism, nonthyroidal illnesses, and newborns were significantly different from normal (P less than 0.01). The mean concentration of T3S in amniotic fluid samples at 15-31 weeks gestation (90 +/- 1.3 pmol/L) was significantly higher than the corresponding value in maternal serum (P less than 0.05) and significantly lower than the corresponding value in newborn cord blood serum (P less than 0.001). Oral administration of sodium ipodate (Oragrafin; 3 g) to two hyperthyroid patients was associated with a 76-190% increase in serum T3S at 8 h, followed by a gradual decrease to a nadir that was 25-60% of the baseline value 2-3 days after ipodate ingestion. We conclude that 1) T3S is a normal component of human serum, and its levels change substantially in several physiological and pathological conditions; 2) sulfation pathway plays an important role in the metabolism of iodothyronines in man; and 3) high serum T3S levels in newborns and low normal levels in pregnancy despite elevated thyronine-binding globulin levels may signify markedly different metabolism of T3S in the mother and fetus.

Adolescent↗

Thyroid hypoechogenic pattern at ultrasonography as a tool for predicting recurrence of hyperthyroidism after medical treatment in patients with Graves' disease.

An abnormal thyroid echographic pattern characterized by a diffuse low echogenicity has been described in Hashimoto's thyroiditis and Graves' disease. The aim of the present work was to study the relationship between thyroid hypoechogenicity and the outcome of treatment for hyperthyroidism with antithyroid drugs in patients with Graves' disease. The study group included 105 patients who underwent a course of methimazole treatment. Thyroid ultrasonography was carried out at diagnosis, and autoantibodies to thyrotropin receptor (TR-ab) were measured at the end of treatment. During the follow-up after methimazole treatment, 87/105 (83%) patients had relapse of hyperthyroidism and 18/105 (17%) were in remission. Recurrence of hyperthyroidism occurred in 71/76 (93%) patients with thyroid hypoechogenicity and in 16/29 (55%) of those with normal thyroid echogenicity (chi 2 = 19.0; p less than 0.0001). Positive TR-ab values at the end of methimazole treatment were found in 59/76 (78%) patients with thyroid hypoechogenicity and in 12/29 (41%) patients with normal thyroid echogenicity (chi 2 = 10.9; p less than 0.0001). Sixty-five/87 (74%) patients with relapse of hyperthyroidism and 6/18 (33%) of those who remained euthyroid were TR-ab-positive at the end of methimazole treatment (chi 2 = 9.8; p less than 0.002). The finding of thyroid hypoechogenicity at diagnosis had higher specificity (0.81) and sensitivity (0.72) with respect to TR-ab positivity at the end of methimazole treatment (0.74 and 0.66 respectively) for the prediction of relapse of hyperthyroidism. Therefore, the evaluation of thyroid echographic pattern can be considered a useful prognostic tool in patients with Graves' disease.

Adult↗

Cardiac rhabdomyoma. Rare cause of fetal death.

Two cases of nonimmune hydrops fetalis and fetal death associated with cardiac rhabdomyoma are reported. Case 1 presented with fetal supraventricular tachycardia, and cardiac rhabdomyoma was accurately diagnosed by fetal echocardiography. Autopsy revealed multiple rhabdomyomata involving the right atrial free wall, the sinoatrial node, and the left ventricle. The left circumflex coronary artery was extrinsically compressed by adjacent tumor tissue, causing left ventricular myocardial infarction. Case 2 had a unique, pedunculated, ball-like rhabdomyoma that almost totally occluded the mitral orifice. The causes of fetal death in patients with cardiac rhabdomyoma are analyzed and the possibility of fetal surgical management is proposed.

Female↗

[Follow-up using echocardiography and ambulatory electrocardiography of patients after excision of intracardiac myxoma].

From November 1968 to May 1990, 56 patients, 19 male and 37 female (mean age 49 +/- 14 years) underwent excision of an intracardiac myxoma (M). M was located into the left atrium in 48 (86%), the right atrium in 6 (11%), and the right ventricle in 2 (3.5%). Operation consisted of excision of the tumor together with its base of attachment. There were 2 early (3.5%) and 2 late (3.7%) deaths. Actuarial survival at 20 years is 91 +/- 4%. Non-invasive reevaluation has been carried out in 44 patients (84%), 39 with left atrial M, 4 with right atrial M, and 1 with right ventricular M. 2-D echocardiography ruled out tumor recurrence in all patients and showed, in those with left atrial M, a reduction in the size of the atrial chamber; on the contrary, left ventricular systolic diameter, diastolic diameter and ejection fraction were unmodified. In 7 patients (15.9%) a residual mild mitral insufficiency was disclosed. In 34 patients 24-hour electrocardiographic monitoring reevaluation showed a low incidence of major supraventricular arrhythmias, late postoperatively (short runs of paroxysmal supraventricular tachycardia in 3 patients, and atrial ectopic rhythm in 1). All these patients had undergone tumor excision by biatrial approach. Based on our results, we conclude that excision of intracardiac myxomas is curative and long-term survival is excellent. Non-invasive reevaluation of patients by 2-D echocardiography and 24-hour electrocardiographic monitoring is mandatory in order to promptly disclose possible complications, particularly tumor recurrence and arrhythmias.

Adolescent↗

Neuropsychological assessment in schoolchildren from an area of moderate iodine deficiency.

Neuropsychological assessment was carried out in schoolchildren from a montane area of Eastern Tuscany (Tiberina Valley). This area was found to be moderately iodine deficient (mean urinary iodine excretion: 39 micrograms/g creatinine), with a cumulative goiter prevalence of 51.9% in schoolchildren aged 6-14 yr (goiter prevalence in the control iodine-sufficient area: 5.6%). No significant differences in serum TT4, TT3, FT4I, TSH levels between the endemic and control areas were found, whereas serum thyroglobulin values were significantly higher in the iodine-deficient area (61 +/- 8 vs 17 +/- 1 ng/ml, p less than 0.01). No differences were found as to the height, body weight and pubertal development in the two areas. Neuropsychological assessment, performed in a representative sample of 50 schoolchildren from the endemic area and 50 schoolchildren from the control area, matched for age, sex and socioeconomical conditions, failed to show major differences between the two groups in the global neuropsychological performance and cognitive levels. However, minor but significant differences were noted in the information vocabulary and coding subtests, at least in children aged 8. Although familial cultural influences might play a role, it would appear that some marginal impairment, with particular regard to motor-perceptual functions, be present in areas of moderate iodine deficiency.

Adolescent↗

Surgical excision of intracardiac myxomas: a 20-year follow-up.

Since November 1968, 54 patients have undergone excision of an intracardiac myxoma, which was located in the left atrium in 46 (85%), in the right atrium in 6 (11%), and in the right ventricle in 2 (4%). There were 35 female and 19 male patients with a mean age of 48 +/- 14 years (range, 7 to 68 years). Four patients were asymptomatic; the others were seen mostly with exertional dyspnea, palpitation, signs of systemic illness, and syncopal episodes. Before operation, embolic episodes occurred in 13 patients with a left atrial myxoma. There were two early (3.7%) and two late deaths (3.8). Actuarial survival at 20 years is 91% +/- 4%, and most of the current survivors are asymptomatic at a mean follow-up of 6.5 +/- 5 years (range, 0.2 year to 20 years). Noninvasive reevaluation was performed with echocardiographic studies in 44 patients and 24-hour electrocardiographic monitoring in 34. No instances of tumor recurrence were observed, and there was a low incidence of major supraventricular arrhythmias late postoperatively. We conclude that excision of intracardiac myxomas is curative and long-term survival is excellent. The transseptal approach provides adequate exposure and allows complete removal of the tumor regardless of its location.

Adolescent↗

Incidence of antibodies blocking thyrotropin effect in vitro in patients with euthyroid or hypothyroid autoimmune thyroiditis.

Autoantibodies blocking the TSH-dependent production of cAMP in thyroid cells (TSH-BAb) have been described in atrophic thyroiditis (AT; idiopathic myxedema) and in neonates with transient hypothyroidism, but their incidence in autoimmune thyroiditis in relation to thyroid status remains to be completely established. To this purpose TSH-BAb were evaluated in a group of 140 consecutive patients with autoimmune thyroiditis, which included 26 cases of AT and 114 subjects with goitrous Hashimoto's thyroiditis (HT); among the goitrous group 27 were euthyroid (HT-E), 32 had subclinical hypothyroidism (HT-SH), and 55 had clinical hypothyroidism (HT-H). TSH-BAb were measured in immunoglobulin G prepared by DEAE-Sephadex A-50 by determining their ability to inhibit TSH-dependent cAMP production in a differentiated strain of cultured rat thyroid cells (FRTL-5). Using this sensitive and reproducible method, TSH-BAb were detected in 12 of 26 (46%) patients with AT, in 1 of 27 (3.7%) subjects with HT-E, in 3 of 32 (9.4%) with HT-SH, and in 20 of 55 (36%) with HT-H. The prevalence of TSH-BAb was higher in AT vs. HT-H (P less than 0.001), HT-SH (P less than 0.001), or HT-E (P less than 0.001), and in HT-H vs. HT-SH (P less than 0.001) or HT-E (P less than 0.001). Mean TSH-BAb levels in AT were higher than those in HT-H (P less than 0.005) and HT-SH (P less than 0.025); the difference was not significant between HT-H and HT-SH. An inverse correlation was found between TSH-BAb levels and estimated goiter weight (P less than 0.005). The results of the present study indicate that 1) in autoimmune thyroiditis TSH-BAb are detectable almost exclusively in hypothyroid patients, their prevalence being higher in overt hypothyroidism than in subclinical thyroid failure; 2) the prevalence of TSH-BAb and their mean levels are higher in hypothyroid patients with AT than in those with HT; and 3) therefore, the presence of circulating TSH-BAb appears to be related to the development of hypothyroidism and thyroid atrophy.

Adult↗