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Biomedical subjects

F Santini

Publications and source records attributed to F Santini.

At least 91 records · Page 5Linked to original sources
PubMed1995

Successful repair of complete sternal cleft associated with congenital heart disease. Report of one case.

Total failure of sternal fusion without other developmental anomalies of the chest and abdominal wall is rare. We report on a 52-year-old man with a total cleft sternum associated exclusively with an ostium secundum type atrial septal defect, a large cono-ventricular septal defect and pulmonary stenosis, who underwent successful surgical repair of the congenital heart disease and of the sternal anomaly by direct approximation of the freshened sternal remnants to the midline without interposition of tissue graft or inert prosthesis. This technique should be considered and attempted first as a better surgical option even in adult patients.

Abnormalities, Multiple↗
PubMed1995

Use of oversized homografts for right ventricular outflow tract reconstruction in infants.

A surgical technique for reducing the size of large diameter homografts in order to make them suitable for right ventricular outflow reconstruction in infants was clinically introduced by us at the Department of Cardiac Surgery, University of Padova in 1990. The method consists of two longitudinal incisions along the oversized homograft root removing one cusp with the relevant part of the aortic annulus and aortic wall. The remaining, flat "bicuspid" homograft is closed into a tube again around a mandrel of appropriate size. Preliminary experiences with the first three patients were excellent and have already been reported. The current study includes five additional patients (two male, three female) ranging in age from 20 days to 11 months (mean 8.3 months) and in weight from 3.2 to 7.4 kg (mean 6.2 kg) who underwent right ventricular outflow tract reconstruction with this surgical technique. There were no operative deaths and no instances of valve related complications at a mean follow up of 18 months. Serial echocardiography showed mild homograft stenosis in one patient (15 mmHg) and mild regurgitation in another. Although a longer follow up is necessary to determine whether the durability of these surgically modified "bicuspid homografts" can match that of the intact valves, we believe that our technique represents a valuable therapeutic alternative at least in the short term to the use of synthetic grafts in infants when an appropriately small homograft is not available.

Bioprosthesis↗
PubMed1994

Detection of antibodies blocking thyrotropin effect using Chinese hamster ovary cells transfected with the cloned human TSH receptor.

Chinese hamster ovary (CHO) cells transfected with the cloned human TSH receptor (CHO-R) were used to develop an assay to detect thyroid autoantibodies blocking the TSH-dependent cAMP production (TSHBAb). The study group included 38 patients with goitrous Hashimoto's thyroiditis (HT) and 47 subjects with atrophic thyroiditis (AT). In the HT group, 8 patients had subclinical hypothyroidism (HT-SH) and 30 had overt hypothyroidism (HT-H). Thirty normal subjects served as controls. Immunoglobulin G (IgG) was prepared from serum by double chromatography on DEAE-Sephadex. CHO-R cells were seeded in 96-well plates and were cultured for 48 h before the assay in RPMI-1640 medium plus 1 mmol/L glutamine, 10% fetal calf serum, and 0.4 g/L geneticin. In the assay for TSHBAb, CHO-R cells were incubated with IgG alone (0.5-2 mg/ml), TSH alone (0.2-625 mU/L), or IgG plus TSH; all samples were diluted in hypotonic medium containing 0.5 mmol/L isobutylmethylxanthine (IBMX). After 2 h of incubation at 37 degrees C in 5% CO2-95% air atmosphere, TSH-stimulation was quantified by measuring extracellular cAMP by a RIA. IgGs from normal subjects did not significantly modify the stimulation of adenylate cyclase produced by TSH, the results obtained ranging between -30% and +18% (mean +/- SD = -3 +/- 14%). All IgGs producing an inhibition greater than 2SD from the mean of controls (> 25%) were considered positive for blocking antibodies. TSHABAb were detected in 1/8 (12.5%) patients with HT-SH, in 7/30 (23.3%) with HT-H and 16/47 (34.0%) patients with AT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Sex-related differences in iodothyronine metabolism in the rat: evidence for differential regulation among various tissues.

Various aspects of thyroid hormone metabolism were examined in vitro in age-matched (experiment I) and weight-matched (experiment II) male and female Sprague-Dawley rats; unless specified otherwise, results were similar in both experiments. The activity and content of iodothyronine 5'-monodeiodinase (type I-MD) in the liver of the female rat were markedly reduced, but there was no sex-related difference in these parameters in the kidney. The activity of the brain type III-MD was also not significantly influenced by the sex of the rat. Hepatic triiodothyronine (T3) sulfation activity in the females was only about 20% of that of the males. However, kidney and brain did not show this decrease in T3 sulfation. Similarly, hepatic T3 sulfate (T3S) desulfation activity was significantly reduced in the liver of the female rat (P < .001), whereas the activity in the kidney was either similar to (experiment I) or higher than (experiment II) that in the male, and the activity in the brain was similar in the two sexes. The mean serum T3S concentration in the female rat was no greater than 25% of the corresponding value measured in the male rat. The mean serum thyroxine (T4) concentration in female rats was similar to that in age-matched males (experiment I), whereas it was somewhat lower than that in weight-matched males (P < .05, experiment II). No significant difference in the mean serum T3 concentration was observed in rats of female and male sex. However, the mean serum thyrotropin (TSH) concentration in the female rat was significantly lower than that in the male.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Cytokines modulate type I iodothyronine deiodinase mRNA levels and enzyme activity in FRTL-5 rat thyroid cells.

Tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interferon-gamma (INF-gamma) have inhibitory effects on thyroid function both in vivo and in vitro. We have studied the effects of these cytokines on type I 5'-deiodinase (5'-DI) mRNA expression and enzyme activity in FRTL-5 cells maintained in standard cell culture medium containing 0 (5H) or 2 mIU/ml bovine TSH (6H). Northern blots were hybridized with 5'-DI cDNA. 5'-DI mRNA levels were reduced to 20% of control values after treating cells with 100 ng/ml TNF-alpha in 6H for 2 days while the corresponding enzyme activity was reduced 50%. Other cytokines, including IL-1beta and interferon-gamma, also significantly inhibited expression of 5'-DI in FRTL-5 cells grown in 6H medium. Because the majority of circulating T3 in the rat is secreted by the thyroid gland, the highly significant decline in the serum T3/T4 ratio following in vivo administration of cytokines may be due to their direct inhibitory effect on thyroidal 5'-DI expression.

Animals↗
PubMed1994

Appearance of thyroid stimulating antibody and Graves' disease after radioiodine therapy for toxic nodular goitre.

A patient with toxic nodular goitre is described in whom radioiodine (131I) therapy paradoxically induced typical Graves' disease. This patient had a goitre with two autonomously functioning nodules suppressing uptake by the remainder of the gland. Circulating thyroid peroxidase antibody indicated the coexistence of focal lymphocytic thyroiditis. Radioiodine therapy was followed by the development of severe and persistent Graves' hyperthyroidism associated with diffuse 131I uptake by the gland. A second administration of 131I produced a further worsening of hyperthyroidism, and the appearance of ophthalmopathy. TSH-receptor antibody and thyroid stimulating antibody were undetectable before 131I, appeared after the first administration of radioiodine, and showed a further increase after the second dose of 131I. We suggest that, in a patient genetically susceptible to thyroid autoimmunity, the release of TSH-receptor antigenic components from follicular cells damaged by radioiodine therapy triggered an autoimmune response to the TSH-receptor, thus turning a toxic nodular goitre into Graves' disease.

Autoantibodies↗
PubMed1994

Studies on the in vitro cytotoxic effect of amiodarone.

Amiodarone, a potent antiarrhythmic drug, contains 37.2% iodine by weight and may induce either hypo- or hyperthyroidism. The high iodine content of amiodarone may be responsible for both complications, but a cytotoxic effect of the drug on the thyroid resulting in thyroiditis has been reported. In the present study the cytotoxic effect of amiodarone was evaluated in three culture systems with different biological properties: 1) a strain of rat thyroid cells (FRTL-5 cells) that maintains most differentiated functions of normal thyroid cells, including an active iodide pump, but an inability to organify iodide; 2) a line of Chinese hamster ovary (CHO) fibroblasts; and 3) freshly prepared primary cultures of human thyroid follicles (hTF) that trap and organify iodide. Cells were radiolabeled with 51Cr and incubated for 24 h with medium alone, medium plus amiodarone (3.75-200 microM), medium plus an iodinated radiographic contrast agent (sodium diatrizoate; 7.5-200 microM), or medium plus potassium iodide (7.5-300 microM). At concentrations ranging from 75-200 microM, amiodarone induced a significant and dose-dependent release of 51Cr in FRTL-5 cells. In contrast, diatrizoate or KI had no cytotoxic effect on FRTL-5 cells. In the same molar concentrations, amiodarone was also cytotoxic in CHO cells. In hTF, the release of 51Cr produced by amiodarone occurred at a lower concentration (37.5 vs. 75 microM) and was significantly greater than that in FRTL-5 cells. The cytotoxic effect of amiodarone in hTF was partially, but significantly, reduced by methimazole, an inhibitor of iodide organification. In the FRTL-5 cell culture system, amiodarone also produced a dramatic inhibition of TSH-stimulated cell growth. This growth-inhibiting effect of amiodarone was evident at low concentrations (3.75-7.5 mumol/liter) of the drug, which did not produce significant cytotoxicity. In conclusion, 1) amiodarone had a cytotoxic effect in CHO fibroblasts, a nonthyroid cell line; 2) this cytotoxic effect occurred in thyroid cells independent of their ability to organify iodide; 3) however, the toxic effect of amiodarone was greater and occurred at a lower molar concentration in freshly prepared human thyroid follicles that trap and organify iodide; and 4) in the latter culture system, methimazole, an inhibitor of iodide organification, partially, but significantly, reduced the cytotoxic effect of amiodarone. These data suggest that thyroid cytotoxicity produced by amiodarone is mainly due to a direct effect of the drug on thyroid cells, but excess iodide released from the drug may contribute to its toxic action.

Amiodarone↗
PubMed1994

[Transient neonatal hypothyroidism and iodine deficiency].

Iodine is the essential constituent of thyroid hormones. Iodine deficiency disorders, ranging from endemic goiter to cretinism, result from low dietary intake of iodine. The fetus and the newborn are more sensitive than adults to a reduced environmental iodine supply, and in iodine-deficient areas, transient neonatal hypothyroidism is frequently observed. This transient thyroid failure may be associated with neonatal goiter. Border-line elevated neonatal TSH levels frequently occur in iodine deficient areas, and result in a higher recalling rate in the screening for congenital hypothyroidism. Iodine prophylaxis is highly effective in preventing the development of iodine deficiency disorders including transient neonatal hypothyroidism. Since iodine prophylaxis in Italy is inadequate, variable degrees of iodine deficiency are still present all-over the Country, and are responsible of a higher incidence of transient neonatal hypothyroidism or hyperthyrotropinemia. Educational programs for the general population, health professionals, and decision makers are essential for a successful iodine prophylaxis. Elimination of iodine deficiency by the year 2000 has been recently pledged by WHO/UNICEF. This goal is feasible if pursued with sufficient vigor and resources.

Congenital Hypothyroidism↗
PubMed1994

[Thyroid autoimmunity and congenital hypothyroidism].

The involvement of thyroid autoimmunity in the pathogenesis of sporadic congenital hypothyroidism is still incompletely understood. While antithyroglobulin and anti-thyroperoxidase antibodies are harmless, the transplacental passage of TSH receptor antibodies with blocking activity from a mother with autoimmune thyroiditis to the fetus is responsible of transient neonatal hypothyroidism in the baby. This is however a rare condition. Thyroid growth blocking antibodies have been described in healthy mothers of children with permanent congenital hypothyroidism due to thyroid dysgenesis, but this observation was not confirmed in other studies including our own. Antibodies producing cell mediated cytotoxicity (ADCC), either transferred from the mother or due to an autoimmune thyroiditis developing in utero, might be involved in the pathogenesis of permanent congenital hypothyroidism. However, this hypothesis requires confirmation in more extensive studies.

Autoimmune Diseases↗
PubMed1994

Aortic valve endocarditis. Determinants of early survival and late morbidity.

BACKGROUND: Aortic valve surgery for endocarditis remains a high-risk procedure. The objective of this study was to analyze the interaction between the various subsets of endocarditis (native, prosthetic, healed, and active), timing of surgery, and their influence on early and late outcomes. METHODS AND RESULTS: During a 20-year period starting January 1972, 200 patients underwent aortic valve replacement for infective endocarditis (age range, 13 to 88 years; median, 53 years). There were 51 (26%) females, and 109 (55%) were in New York Heart Association functional class IV before surgery. Native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE) were present in 132 (66%) and 68 (34%) patients, respectively. Surgery was required in 120 (60%) during the active phase (AE) and 80 (40%) during the healed phase (HE) of endocarditis. The main indication for surgery in the healed group was progressive congestive heart failure. The indications for the active group were congestive heart failure (68%), continuing active sepsis (70%), echocardiographic vegetation (28%), peripheral emboli (30%), and arrhythmias (13%). Streptococcal infections predominated in NVE, staphylococcal in PVE and AE; culture-negative endocarditis predominated in the healed group. Isolated aortic valve surgery was performed in 68% of the patients, and concomitant procedures (32%) included mitral valve and coronary bypass procedures. The overall operative mortality (OM) was 12.5%. The OM was 7.5% and 22% for NVE and PVE, respectively (P = .004), and 7% for HE versus 15% for AE (P = .06). The OM for early PVE was 33% versus 18% for late PVE (P < .05). Multivariate logistic regression analysis identified PVE and New York Heart Association functional class IV to be independent predictors for early death. Recurrent endocarditis occurred 26 times in 24 patients (11 early, 13 late), with three operative deaths in the early group, all due to residual staphylococcal infections. Freedom from recurrent endocarditis was significantly different between HE (96 +/- 3% and 86 +/- 6% at 5 and 10 years, respectively) and AE (89 +/- 3% and 83 +/- 4%, respectively (P = .02). Long-term survival for discharged patients was 81 +/- 3% and 63 +/- 5% at 5 and 10 years, respectively, with no significant difference between NVE, PVE, AE, and HE. CONCLUSIONS: These data suggest that for active endocarditis, surgery should be delayed to achieve a healed status provided there is no pressing need for immediate surgery. Patients with staphylococcal endocarditis, particularly on a prosthesis, should be operated on sooner and should be covered with antibiotics for an extended period to prevent recurrent PVE. This study stresses the need for aggressive antibiotic prophylaxis, particularly in the presence of a prosthesis.

Aortic Valve↗
PubMed1994

Cardiac myxoma of the tricuspid valve: description of a case and review of the literature.

Although myxomas are the most common cardiac neoplasms in the adult population, they are very rare in pediatric patients. Tricuspid valve myxomas are even more exceptional at all ages, with only 16 cases being reported in the literature. We describe the case of a 10-year-old boy with a myxoma of the tricuspid valve, who was successfully operated without valve replacement.

Child↗
PubMed1993

Tyrosine phosphorylation of a mitogen-activated protein kinase-like protein occurs at a late step in exocytosis. Studies with tyrosine phosphatase inhibitors and various secretagogues in rat RBL-2H3 cells.

Several inhibitors of tyrosine phosphatases, which included vanadate/H2O2, phenylarsine oxide, and diamide, blocked exocytosis in basophilic RBL-2H3 cells that had been transfected with the gene for the muscarinic m1 receptor. Because this block was observed whether the secretagogue acted through receptors (i.e. antigen and the muscarinic agonist, carbachol) or by direct activation of intracellular mechanisms (i.e. A23187, A23187 in combination with phorbol 12-myristate 13-acetate, and thapsigargin), the inhibitors appeared to act at a step distal to the mobilization of Ca2+ and activation of protein kinase C. All secretagogues caused the tyrosine phosphorylation of a 40-kDa protein, whereas the inhibitors caused a hyperphosphorylation of this protein. Therefore, both tyrosine kinase and phosphatase activities appear to regulate this phosphorylation which may, in turn, regulate secretion. The 40-kDa protein was identified as a mitogen-activated protein kinase-like protein on the basis of its reactivity to anti-mitogen-activated protein kinase antibodies. In addition, when cells were stimulated the tyrosine phosphorylated and the immunoreactive protein comigrated as a doublet on one-dimensional and as multiple phosphorylated forms on two-dimensional gel-electrophoretic systems.

Actins↗
PubMed1993

Application of fresh and cryopreserved homografts harvested from transplant patients for correction of complex congenital heart disease.

In recent years, the use of homograft tissue in cardiac surgery has increased so that supply is limited. Since October 1990, aortic and/or pulmonary valves were collected from 17 transplant recipients at the Department of Cardiovascular Surgery of the University of Padova Medical School (11 male, 6 female, mean age 43.4 years, range 11 months to 61 years). The indications for transplant were dilated cardiomyopathy in 7, and end-stage ischemic heart disease in the remaining 10 patients. Twelve such valves have been subsequently reimplanted either as fresh or as cryopreserved valved homografts in the repair of different forms of congenital heart disease, by means of different tailoring techniques (7 male, 5 female; mean age 4.8 years [range 1 day to 18 years]; transposition of the great arteries = 5 cases; tetralogy of Fallot = 3 cases; hypoplastic left heart syndrome = 2 cases; double outlet right ventricle = 1 case; truncus arteriosus = 1 case). Overall, early mortality was 25%. None of these deaths could be related to the use of homografts. There have been no instances of valve related complications among nine patients surviving surgery at a mean follow-up of 11 months. All patients having heart explanted should be regarded as potential sources for aortic and pulmonary homografts.

Adolescent↗
PubMed1993

Thyromimetic effects of 3,5,3'-triiodothyronine sulfate in hypothyroid rats.

Several parameters of the effects of thyroid hormone were examined in hypothyroid thyroidectomized (Tx) rats treated with T3 sulfate (T3S) or T3 [0.46 (low dose) or 2.3 (high dose) nmol/day for 10 days, ip]. Tx rats showed a marked degree of growth retardation, which improved significantly after treatment with both doses of T3S and T3. The mean serum GH level was markedly reduced in Tx rats, and it improved significantly to similar levels after treatment with the high dose of T3S and the low dose of T3. Type I monodeiodinase (MD) activity was markedly reduced in liver and kidney tissues of Tx rats. It increased significantly in Tx rats treated with the high dose of T3S; the latter values were similar to those observed in Tx rats treated with the low dose of T3. Hepatic and renal type I MD activities increased to supranormal levels in Tx rats treated with the high dose of T3. Cardiac outer ring (5') monodeiodination of 3',5'-diiodothyronine to 3'-monoiodothyronine was also significantly reduced in Tx rats, but it improved significantly only after treatment with the high dose of T3. Type III 5-MD activity was significantly reduced in the cerebral cortex of Tx rats. It was restored to normal in Tx rats treated with the high dose of T3S and both doses of T3. Serum TSH, markedly elevated in Tx rats, was appreciably reduced only in rats treated with the high dose of T3. In another study, significant suppression of serum TSH was observed when Tx rats were treated with T3S (11.5 nmol/day) or T3 (2.3 nmol/day) for 3 days. We conclude that administration of T3S to hypothyroid rats produces thyromimetic effects, with a potency approximately one fifth that of T3.

Animals↗
PubMed1993

A study of the 3,5,3'-triiodothyronine sulfation activity in the adult and the fetal rat.

We have employed a new in vitro assay for study of the T3 sulfation activity in rat tissues. The assay measures by RIA the generation of T3 sulfate (T3S) during incubation of T3 with cytosol of rat tissues as the source of phenol sulfotransferase(s) and 3-phosphoadenosine-5'-phosphosulfate as the sulfate donor. The conversion of T3 to T3S proceeded rapidly for 30 min at 37 C, and the optimal pH of the reaction was 8.0. Heating the cytosol at 44 C for 15 min decreased T3S production to 63% of its value at 37 C. T3 sulfation activity was plentiful in rat liver, brain, and kidney, but little activity was demonstrable in other tissues. The Km and maximum velocity of the hepatic conversion of T3 to T3S were 114 microM and 159 pmol/mg protein.h, respectively. There was a marked inhibition of the conversion of T3 to T3S with salicylamide, 3'-monoiodothyronine, thyronine, and rT3; the IC50 of these inhibitors approximated 15, less than 0.1, 9.5, and 43 microM, respectively. On day 17 of gestation, the T3 to T3S conversion activity was more abundant in fetal skin than in other fetal tissues. However, the activity decreased in fetal skin while it increased in fetal liver, kidney, and brain nearer to term on day 20. Placenta demonstrated lower T3 to T3S conversion activity than several fetal or maternal tissues. There was no effect of hypothyroidism or hyperthyroidism on T3 sulfation activity. We conclude that T3 sulfation activity in the rat is 1) most abundant in liver, kidney, and brain tissues of the adult; 2) inhibited more avidly by 3'-monoiodothyronine than other thyronines; 3) very abundant in fetal skin early in gestation; and 4) little affected by the thyroidal status of the animal.

Animals↗
PubMed1993

A radioimmunoassay for measurement of thyroxine sulfate.

A highly sensitive, specific, and reproducible RIA has been developed to measure T4 sulfate (T4S) in ethanol extracts of serum. rT3 sulfate (rT3S) cross-reacted 7.1%, and T3S cross-reacted 0.59% in the RIA; T4, T3, rT3, and 3,3'-diiodothyronine cross-reacted 0.004% or less. The recovery of nonradioactive T4S added to serum averaged 95%. The detection threshold of the RIA was 18 pmol/L. The coefficient of variation averaged 6.9% within an assay and 12% between assays. T4S was bound by T4-binding globulin and albumin in serum. The free fraction of T4S in four normal sera averaged 0.06% compared to a value of 0.03% for T4 (P < 0.001). The serum concentration of T4S was (mean +/- SE) 19 +/- 1.2 pmol/L in normal subjects, 33 +/- 10 in hyperthyroid patients with Graves' disease, 42 +/- 15 in hypothyroid patients, 34 +/- 6.9 in patients with systemic nonthyroidal illnesses, 21 +/- 4.3 in pregnant women at 15-40 weeks gestation, and 245 +/- 26 in cord blood sera of newborns; the value in the newborn was significantly different from normal (P < 0.001). The mean concentration of T4S in amniotic fluid samples at 15-38 weeks gestation was 106 +/- 22 pmol/L (cf. normal adults; P < 0.001). Administration of sodium ipodate (Oragrafin; 3 g, orally) to hyperthyroid patients was associated with a transient increase in serum T4S. The T4S content of the thyroid gland was less than 1/4000th that of T4. We conclude that 1) T4S is a normal component of human serum, and its levels are markedly increased in newborn serum and amniotic fluid; and 2) the sulfation pathway plays an important role in the metabolism of T4 in man.

Blood Proteins↗