Local endovascular treatment of aortic aneurysms. From operating theater to lab bench.

Current treatment of aortic abdominal aneurysms by conventional surgery or endoprosthesis is flawed by high post-operative mortality and unpredictable durability of haemodynamic exclusion, respectively. We have developed endovascular approaches with cell and gene transfer, aimed at controlling further diameter expansion in an animal model of already-developed aneurysms in rats. Preliminary results suggest that both cell and gene endovascular therapy can be used to control expansion of aneurysms generated by inflammation and proteolytic destruction of the aortic wall.

[Development and repair of vessels from bone marrow stem cells in the adult: from biology to clinical practice]. / Le développement et la réparation des vaisseaux à partir de cellules de la moelle osseuse chez l'adulte. De la biologie à la clinique.

In addition to its role in hematopoiesis, bone marrow appears to be a reservoir of stem cells that can differentiate into components of vessel wall. Upon stimulation by factors such as tissue ischemia, bone marrow stem cells can enter into circulating blood, and incorporate into areas of vascular development. Animal models suggest that bone marrow is a cellular source for tissue repair and/or regeneration. Data from humans, and clinical trials using bone marrow stem cells for the treatment of chronic ischemia in limbs and myocardium, support the view that stem cells may represent a new tool for the treatment of ischemia.

Extremely high levels of estradiol and testosterone in a case of polycystic ovarian syndrome. Hormone and clinical similarities with the phenotype of the alpha estrogen receptor null mice.

A 19-year-old nulliparous hirsute woman was evaluated for the very high serum levels of testosterone (T) and estradiol (E2) measured in an outside laboratory. Menarche had occurred at 11 years and was followed by regular menses. We confirmed the high levels of T (9-16 ng/ml, nv 0.2-0.8) and E2 (>1,000 pg/ml, nv 30-120). LH and FSH were consistently high (73-118 mU/l and 18-29 mU/l, respectively; LH/FSH ratio=4.1-4.7) and responsive to iv GnRH (LH baseline=118 mU/I, 30 min=290; FSH baseline=25 mU/l, 30 min=46). The unstimulated values contrasted with those (LH=12, FSH=8 mU/I) measured in the outside laboratory, suggesting antigenically anomalous gonadotropins. 17-OH-progesterone was normal (0.5 ng/ml). After 1 mg dexamethasone, serum cortisol was normally suppressed (24-->0.4 microg/dl), T declined minimally (9-->8.6 ng/ml) and E2 remained high (>1,000 pg/ml). An exploratory laparotomy was performed, and two enlarged ovaries with multiple cysts as in a typical polycystic ovarian syndrome (PCOS) were seen. Before the wedge resection of the ovaries, hormones were assayed in the ovary veins (right ovary: T=30 ng/ml, Pg=17 ng/ml, E2=>5,000 pg/ml; left: T=14 ng/ml, Pg=14 ng/ml, E2=>5,000 pg/ml). Histologically, the follicle cysts showed luteinization of the theca interna; there was no evidence for ovary tumor in either ovary. After 21 days of 35 microg ethynyl-E2+2 mg cyproterone acetate (CA), E2=3,000 pg/ml, T=1.4 ng/ml, LH=10.5 mU/l and FSH=4.1 mU/I. After three cycles of the said therapy (but with 50 mg CA in the first 10 days of each cycle), E2 was 1,600 pg/ml, T 1.7 ng/ml, LH 7.1 and FSH 4.6 mU/I. Based on similarities with the phenotype of the alpha estrogen receptor knockout female mice (alphaERKO), one possible explanation for the puzzling clinical and biochemical picture of our patient is resistance of (alphaER to estrogens. This is the first case of PCOS with extremely high E2 and T. Thus, the differential diagnosis of high levels of E2 +/- T should include PCOS.

Euthyroid hyperthyrotropinemia secondary to hyperestrogenemia in a male with congenital adrenal hyperplasia.

A 10-year-old boy with congenital adrenal hyperplasia and associated hyperplastic testicular adrenal rests had high serum concentrations of 17-OH progesterone (17-OHP), estradiol (E2), testosterone (T), and basal and TRH-stimulated TSH and PRL, but normal thyroid hormones (T3, T4, FT3, FT4) and thyroxine-binding globulin (TBG). Upon dexamethasone therapy, steroid hormones returned progressively toward normal as did both PRL and TSH; PRL declined faster than TSH. Serum E2 correlated better with PRL than with TSH. Therefore, the responsiveness of the thyrotrophs to the ambient concentration of E2 is lower and slower than that of the lactotrophs. In the context of the inconclusive data on the role of estrogens in controlling the secretion of TSH in humans, our case suggests that E2 does stimulate the secretion of basal and TRH-elicited both TSH and PRL, and that this positive action is unopposed by T. In contrast, T antagonizes the estrogen-induced increase in serum TBG. We also postulate that E2 might impair the bioactivity of TSH, in order to explain (i) the approximate 3-fold increase in serum TSH coexisting with a normally sized (rather than enlarged) thyroid and normal (rather than increased) serum thyroid hormones, and (ii) the inability of TRH-stimulated TSH to acutely raise FT3 serum levels.

Testicular adrenal rests: evidence for luteinizing hormone receptors and for distinct types of testicular nodules differing for their autonomization.

We report one patient with 21-hydroxylase deficiency and associated bilateral macro-orchidism caused by nodular hyperplasia of testicular adrenal rests (TAR). The boy, referred to us when 10 years old, was born with bilateral cryptorchidism that was treated unsuccessfully with i.m. injections of human chorionic gonadotropin (hCG) and later on with orchidopexy. He was treated with oral dexamethasone (0.625 mg per day) for the following 13 years. After one year, there was a marked reduction in steroid hormone levels (17-hydroxyprogesterone (17-OH P) from 27.2 to 1.2 nmol/l, testosterone from >104 to 4.8 nmol/l, estradiol (E(2)) from 481 to 33 pmol/l). After the same period of time, both testicular volume and nodularity decreased: from 45 to 18 ml and from numerous to four nodules in the right testis, and from 40 to 13 ml and from numerous to three nodules in the left testis. At the third year, there were transient increases in serum gonadotropins, testicular volume (right testis = 25 ml, left testis = 20 ml) and steroid hormones, including cortisol (serum ACTH and dehydroepiandrosterone sulfate remained suppressed). At the fourth year of follow-up, there were still four nodules in the right testis and three in the left testis. The LH-dependency (which implies possession of LH/hCG receptors) of these nodules was also substantiated by their steroidogenic response to an acute i.m. hCG test. An exogenous ACTH stimulation test increased serum 17-OH P and cortisol. Since these nodules, unlike the majority of those present initially, were not suppressed by the corticosteroid therapy and since they were not detected when the patient returned for control at 23 years of age, they had partial autonomy from ACTH. At 23 years of age, the patient had a single nodule in the right testis (right testis volume = 13 ml, left testis volume = 10 ml), which should have accounted for the consistent difference in size between the two gonads. Serum LH was about 7 mU/l and FSH about 23 mU/l. The responsiveness of plasma steroid hormones to hCG had changed quantitatively and qualitatively. Secretion of cortisol was absent, secretion of 17-OH P and testosterone was reduced, and secretion of E(2) was much increased. The ACTH stimulation test showed that serum cortisol did not respond, while the other steroids responded in the order of 17-OH P>E(2)> testosterone. We conclude that there were three different groups of TAR when the patient was already 10 years old: (i) ACTH-sensitive (the majority), (ii) partially ACTH-insensitive but LH/hCG-sensitive (three nodules in the left testis and three in the right testis), (iii) almost entirely ACTH-insensitive and partially hCG-insensitive (a single nodule in the right testis). Probably, the never suppressed gonadotropin levels (presumably due to the bilateral testicular damage subsequent to the cryptorchid state) and the hCG therapy were major etiological factors for the appearance of the second and third population of TAR.

[Erectile dysfunction of vasculogenic origin: ultrastructural evaluation of cavernous myo-endothelial unit as prognostic index of penile revascularization]. / Disfunzioni erettili di natura vasculogenica: valutazione ultrastrutturale dell'unità mio-endoteliale cavernosa quale indice prognostico per la rivascolarizzazione peniena.

The authors focus on the myoendothelial unit of the cavernous tissue, as they believe it to be of primary importance for the erectile event. The operations aimed at penile revascularisation were functionally unsuccessful, notwithstanding the haemodynamic resumption. This could be due to the myoendothelial unit not being perfectly integral. The authors have carried out 90 fine needle biopsies of the cavernous bodies in patients with erectile dysfunctions. These were evaluated using an ultra-microscope. The results of this ultra-structural analysis have highlighted various degrees of regressive phenomena, which can be linked to the severity and the duration of the symptom. The authors conclude by proposing that FNB should be used as a diagnostic tool for the selection of patients eligible for penile revascularisation.

[The conversion of a modified Fontan procedure to a total extracardiac cavo-pulmonary conduit. The Medico-Surgical Cardiology Group]. / Conversione della procedura di Fontan modificata a connessione cavopolmonare totale extracardiaca. Raggrupamento di Cardiologia Medico Chirurgica.

BACKGROUND: After a modified Fontan procedure with atriopulmonary or atrioventricular conduit, some patients present stress intolerance, supraventricular arrhythmia, recurrent pleuropericardial or ascitic effusions, and protein-losing enteropathy, all of which are signs that the previous procedure has failed. The aim of this study was to evaluate the midterm outcome after surgical therapy for this condition. MATERIAL AND METHODS: Between August 1994 and December 1997, nine patients (6 males and 3 females), age 10 to 39 (mean 21.5) years, underwent conversion of previous modified Fontan procedure to total extracardiac cavo-pulmonary connection. Time from the previous procedure was 6 to 18 years (mean 10). Diagnosis was tricuspid atresia with pulmonary stenosis (n = 2), double-inlet left ventricle and concordant ventriculoarterial connection (n = 3), double-inlet left ventricle and discordant ventriculoarterial connection (n = 3), Holmes heart (n = 1). Nine patients presented decreased stress tolerance, seven had arrhythmia, five had pleuropericardial effusions and two had protein-losing enteropathy. In all but one patient, right atrial pressure was higher than 15 mmHg, while in six patients the cardiac index was less than 2 l/min/m2. A polytetrafluoroethylene non-valved conduit was interposed between the inferior vena cava and the right pulmonary artery for conversion in all patients. A bidirectional cavo-pulmonary anastomosis (modified Glenn) was associated in all patients. Evaluation was done by NYHA Class and by an arbitrary score assigned to patients based on 7 parameters. RESULTS: There was no perioperative mortality. All patients were clinically improved at a mean follow-up of 24 months (range: 3 to 46). No patient had effusions, and the arrhythmias disappeared in 4 patients and were controlled by medical therapy in one. The two patients with protein-losing enteropathy improved markedly within 30 days and the score dropped below 10 points. CONCLUSIONS: The conversion of the modified Fontan procedure to total extracardiac cavo-pulmonary connection improves clinical condition by decreasing the right atrium-pulmonary gradient and right atrial preload, and by providing a laminar cavo-pulmonary flow without any need for intracardiac anastomoses. This procedure should be undertaken early in this subset of patients, before ventricular failure ensues.

[The role of a bidirectional cavopulmonary anastomosis in the correction and palliation of complex congenital cardiopathies]. / Ruolo dell'anastomosi cavo-polmonare bidirezionale nella correzione e palliazione delle cardiopatie congenite complesse.

Between May 1990 and January 1998, 68 patients underwent bidirectional cavo-pulmonary anastomosis. We evaluated all patients in whom the bidirectional cavo-pulmonary anastomosis was associated with additional pulmonary flow (group A) and those in whom it was associated with biventricular repair (group B). Group A included 23 patients (33.8%), 14 males and 9 females, mean age 25 years and 6 months (range 4 months-16 years). Diagnoses were double outlet right ventricle (6), univentricular heart (6), tricuspid atresia (5), congenitally-corrected transposition of the great arteries with ventricular septal defect and pulmonary stenosis (3), right isomerism (2) and pulmonary atresia with atrioventricular canal (1). Group B included 13 patients (19.1%), 6 males and 7 females, mean age 13 years and 7 months (range 1 year-37 years). Diagnoses were pulmonary atresia with intact ventricular septum (4), Ebstein's anomaly (3), tetralogy of Fallot (3), atrioventricular canal (1), hypoplastic right ventricle (1), and pulmonary and tricuspid insufficiency (1). Four patients (17.3%) in group A died in the postoperative period, whereas there was no postoperative mortality in group B. Follow-up data were available in 31 patients (19 from group A, 13 from group B). Mean follow-up was 1 year and 6 months (range 30 days to 6 years). Evaluation was done by NYHA class functional status. In group A, 14 patients are doing well (NYHA I or II), while five patients (26.3%) underwent Fontan operation with one death. All group B patients are currently doing well (NYHA class I or II). In group A, complications were pericardial effusion (7), transient superior vena cava syndrome (5), pleural effusion (4), chylothorax (1) and rhythm disturbance (1). Complications in group B involved neurological events (2), pleural effusion (1) and rhythm disturbance (1). Bidirectional cavo-pulmonary anastomosis can be associated with additional pulmonary flow with good short- and intermediate-term outcome. Concern remains for the ability to properly regulate the amount of effective pulmonary blood flow. Bidirectional cavo-pulmonary anastomosis can be associated with biventricular repair in patients with diminutive right ventricles, amenable to anatomic complete correction, with good clinical outcome.

Dissociation between adrenarche and gonadarche in two longstanding hypothyroid youngsters.

An evident dissociation between adrenarche and gonadarche was found in two longstanding hypothyroid youngsters, one male and one female, with advanced gonadal development and absent sexual hair. This discrepancy rapidly vanished after the institution of thyroxine substitutive treatment. These case reports underline the important relationships existing between thyroid function and endocrine systems involved in the regulation of adrenarche and gonadarche.

[Functional evaluation of cystic thyroid nodules]. / Valutazione funzionale dei noduli tiroidei cistici.

7 patients (age between 22 and 52 years, mean 38.2 +/- 10.6 SD) with cystic nodules have been subjected to the same diagnostic screening (scintiscanning and echography, needle aspiration); in every subject hormonal pattern has been studied at the cyst and periphery level. The Authors found very high TG levels in the cyst's fluid, perhaps due to an increased sensitiviness to the thyrotropic hormone, and an rT3/T4 increased at periphery level, probably because an enhancement of mechanisms connected to the reuptake of iodine. These reports outline the great importance in the induction and development of cystic nodules of changes related to the enzymatic steps of iodination and coupling.

[Intraoperative functional study of unilateral cold thyroid nodules]. / Studio funzionale intraoperatorio dei noduli tiroidei freddi unilaterali.

The authors studied 7 patients (age between 22 and 52 years, mean 40.2 +/- 6.55 S.D.) with single or multiple solid nodules, localized in the same thyroid lobe. All subjects performed scintiscanning and echography for evaluating the nature of nodules. During the thyroidectomy the hormonal pattern has been studied in the venous blood of both lobes (inferior thyroid and jugular veins, homo and heterolateral). The authors found a significant decrease of T3 and T4 values with increased T3/T4 ratio at the nodular level. This report could be related to an hypothetical alteration of iodination mechanisms, maybe due to an intrinsic defect of oxidative mitochondrial systems.

[Serum prolactin in obese subjects with and without glucose intolerance]. / Comportamento della prolattinemia nei soggetti obesi con e senza intolleranza ai carboidrati.

Basal values of H-Prl have been assayed with reproducible RIA in two accurately selected group of subjects: 1) obese with latent glucose intolerance; 2) obese without glucose intolerance. In these patients have been valued also IRI and blood glucose (GOD-POD Biochemia). The data reported in this paper show that therein't correlation between basal H-Prl values and difference obese -- normal of IRI concentrations neither in non-diabetics nor in pre-diabetics obese. It indicate that the H-Prl not plays a controinsular role in obese-prediabetics subjects. No difference in basal values of H-Prl we found in the examined patient obese pre- and not-diabetics.

[Serum prolactin in obese subjects with glucose intolerance before and after treatment with phenformin]. / Comportamento della prolattinemia in soggetti obesi con intolleranza ai carboidrati prima e dopo trattamento con fenformina.

10 obese subjects with latent glucose-intolerance we studied before and after a "short term" treatment with an oral antidiabetic drug, phenformina (100 mg/day for 14 days). The parameters we evaluated, were: basal IRI, C-peptide immunoreactive (IRCP), IRCP/IRI ratio, areas elicited by values of IRI after oral glucose tolerance test (OGTT), basal H-Prl, before and after the phenformin (F) treatment. Our data show that F decreases the basal IRI values but not IRCP values, so the IRCP/IRI ratio is significantly higher. No difference is found in the basal H-Prl values.