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In complex velocity models, such as below rugose salt bodies, wavefield continuation migration usually is superior to Kirchhoff methods because of multi-pathing, sharp velocity contrasts, and the bandlimited nature of [...]

Structural imaging and event location require an accurate estimation of the seismic velocity. However, active seismic surveys used to estimate it are expensive and time‐consuming. During the last decade, fiber‐optic‐based distributed acoustic sensing has emerged as a reliable, enduring, and high‐resolution seismic sensing technology. We show how downhole distributed acoustic sensing passive records from the San Andreas Fault Observatory at Depth can be used for seismic velocity estimation. Using data recorded from earthquakes propagating near‐vertically, we compute seismic velocities using first‐break picking as well as slant stack decomposition. This methodology allows for the estimation of both Pand Swave velocity models. We also use records of the ambient seismic field for interferometry and Pwave velocity model extraction. Results are compared to a regional model obtained from surface seismic as well as a conventional downhole geophone survey. We find that using recorded earthquakes, we obtain the highest Pwave model resolution. In addition, it is the only method that allows for Swave velocity estimation. Computed Pand Smodels unravel three distinct areas at the depth range of 50‐750 m, which were not present in the regional model. In addition, we find high VP/VSvalues near the surface and a possible VP/VSanomaly about 500 m deep. We confirm its existence by observing a strong S‐Pmode conversion at that depth. A seismically active area is recorded using distributed acoustic sensing of a downhole fiberWe estimate P‐ and S‐ wave velocities using fiber data and compare them with conventional surveysVelocity analysis unveils a geological structure at the San Andreas Fault Observatory at Depth location

Levothyroxine (L-T4) is recommended as lifelong replacement therapy for hypothyroidism. Recent clinical and experimental data support the addition of levotriiodothyronine (L-T3) treatment in some selected hypothyroid patients when their symptoms persist and their quality of life remains impaired despite adequate L-T4 monotherapy. An increase in L-T3 prescriptions has been recently observed in Italy due to availability of different L-T3 formulations, making it possible to clinicians to prescribe L-T3 alone or in combination with L-T4. The aim of the present position statement was to define the correct clinical indications, schedule, duration of treatment and contraindications of combined treatment with L-T4 and L-T3 in hypothyroid patients in an attempt to guide clinicians and to avoid potential adverse effects of overtreatment.

We show that a reliable and statistically significant group velocity time‐lapse difference between 2004 and 2010 can be retrieved from ambient seismic noise in an offshore hydrocarbon exploitation setting. We performed a direct comparison of Scholte wave group velocity images obtained using regularized tomography. We characterize the expected variation in group velocity images from the 2004 or 2010 recordings that result from fluctuations in the cross correlations by looking at cross correlations of portions of the recordings. We prove that the time‐lapse difference is statistically significant. The time‐lapse group velocity image from ambient noise data shows strong similarities with a time‐lapse phase velocity map obtained from controlled source data. The most striking features are a northern and a southern group velocity increase due to compaction and subsidence as a result of reservoir production. We present a new approach for time‐lapse seismic monitoringWe apply the new method to a large data set in a hydrocarbon exploration settingWe detect velocity changes in the subsoil caused by reservoir compaction

Background:Obesity and insulin resistance predispose individuals to the development of both metabolic syndrome and non-toxic nodular thyroid diseases. Aim:The aim of this observational, cross-sectional study is to evaluate the relationship between metabolic syndrome and multinodular non-toxic goiter in an inpatient population from a geographic area with moderate iodine deficiency. Subjects and methods: We examined 1422 Caucasian euthyroid inpatients. Thyroid volume was determined by ultrasound of the neck. A fine-needle aspiration biopsy was performed to evaluate single thyroid nodules and dominant nodules ≥15 mm in euthyroid multinodular goiter. The diagnosis of metabolic syndrome was made according to the criteria of the American Heart Associaion/National Heart, Lung, and Blood Institute. Results:Of the sample, 277 patients had clinical evidence of multinodular non-toxic goiter, 461 met the criteria for the diagnosis of metabolic syndrome, and 132 were found to have both conditions. After adjusting for age, gender, body mass index, nicotinism, parity, alcohol intake, thyroid function, and metabolic syndrome-related pharmacological treatment, metabolic syndrome was found to be an independent risk factor for the occurrence of multinodular non-toxic goiter. The relationship between metabolic syndrome and multinodular non-toxic goiter was apparent in both men and women. Conclusions:In this study of euthyroid inpatients, we demonstrate that metabolic syndrome is an independent risk factor for the occurrence of multinodular non-toxic goiter in a geographic area with moderate iodine deficiency. We propose that patients meeting the criteria for metabolic syndrome should be screened for the presence of multinodular non-toxic goiter.

The identification of patients with von Hippel-Lindau (VHL) disease dictates accurate genetic counseling of family members, whereas screening for early detection of visceral and neurological involvement is usually performed by a combination of radiological and nuclear medicine techniques such as ultrasonography or contrastenhanced computed tomography of the upper abdomen, magnetic resonance imaging of the central nervous system and 131I-metaiodobenzylguanidine-scintigraphy. The role of 111-indium-diethylenetriaminepentaacetic acid [111ln-DTPA0] octreotide scintigraphy in this clinical context has never been investigated. Here, we report imaging findings in a VHL patient and in 3 consecutive family members undergoing clinical and radiological screening that included [111ln-DTPA0] octreotide scintigraphy in addition to the above-mentioned procedures. Somatostatin receptor expression was investigated in vitroby immunohistochemistry in pancreatic tumor sections. On the basis of in vivoand in vitrofindings, octreotide long-acting release treatment followed by 90Y-1,4,7,10-Tetraazacyclododecane-N, N′, N′’, N‴-tetraacetic acid (DOTA0)-Tyr3-octreotide led to a lack of progression in this patient although this result is a possibility which needs to be proved by further investigation and longer follow-up. The results of this study suggest that [111In-DTPA0] octreotide scintigraphy may be helpful in the routine work-up of VHL patients for diagnostic and therapeutic purposes.

Herein we report on a young girl with recurrent, functioning paraganglioma of the organ of Zuckerkandl and severe and sustained arterial hypertension (systolic pressure >200, diastolic pressure >120 mmHg); with evidence of cardiac damage induced by chronic cathecolamine excess. She promptly and steadily improved after the institution of doxazosin (6 mg/day) plus atenolol (50 mg bid) treatment. This case demonstrates that a correct therapeutic strategy in the longterm management of patients with inoperable catecholamine-producing neuroendocrine tumors (pheochromocytomas and paragangliomas) can maintain arterial pressure in the normal range and reverse the cardiac damage induced by chronic cathecolamine excess.

OBJECTIVES: To ascertain whether myocardial contractility and total arterial stiffness are significantly altered in human thyrotoxicosis, and to what extent they are affected by acute beta(1)-adrenergic blockade. METHODS: Doppler-echocardiography was used to assess left ventricular (LV) structure and function, hemodynamics and total arterial stiffness in untreated overt hyperthyroid patients before and 2 h after 5 mg bisoprolol given orally compared with age- and sex-matched healthy euthyroid controls. RESULTS: Compared with controls, untreated patients (n=20) had a higher heart rate (HR) and LV stroke index (SI), which were associated with higher pulse pressure (PP), larger LV end-diastolic volume index (EDVI, an index of preload,+11%, P<0.05), marginally increased stress-corrected LV midwall fractional shortening (MWS, an index of myocardial contractility,+5%; P=0.066), and shorter isovolumic relaxation time (IVRT). These changes resulted in a higher cardiac index (CI) and a lower systemic vascular resistance (SVR), which were associated with fairly normal mean blood pressure (BP) but higher PP/stroke volume (an index of total arterial stiffness,+29%; P<0.01). After bisoprolol, compared with controls, the randomly treated patients (n=10) had comparable HR but additionally increased SI; PP remained enhanced, EDVI was further enlarged (+26%, P<0.001), stress-corrected MWS was substantially unchanged, and IVRT remained shorter. Overall, these effects attenuated the high-output state, which was associated with normalization of PP/stroke volume without changes of mean BP. CONCLUSIONS: In human overt hyperthyroidism, myocardial contractility does not play a major role in increasing LV performance, which is instead predominantly sustained by increased preload with enhanced LV diastolic function. In addition, human thyrotoxicosis is associated with increased total arterial stiffness despite fairly normal mean BP. In this scenario, acute beta(1)-adrenergic blockade blunts the cardiovascular hyperkinesia predominantly by slowing HR - a process that is associated with normalization of total arterial stiffness.

BACKGROUND: Gender differences in tumor size are supposed to exist in hyperprolactinemia since microadenomas are more commonly found in women and macroadenomas in men. Whether this reflects only a delay in diagnosis in men or a true gender difference in tumor pathogenesis is still unclear. OBJECTIVE: To prospectively analyze gender differences in the presentation and response to cabergoline treatment in 219 consecutive newly diagnosed patients with hyperprolactinemia. DESIGN: An open prospective design. SUBJECTS: Of the 219 patients of which 145 were women; 107 patients had macroprolactinoma, 97 had microprolactinoma, and 15 had non-tumoral hyperprolactinemia. METHODS: Presenting clinical symptoms, prolactin levels and tumor size at magnetic resonance imaging were measured before and 3-6 Months after cabergoline therapy. RESULTS: Prevalence of microprolactinomas (56% vs 22%, P=<0.0001) and non-tumoral hyperprolactinemia (10% vs 0%, P=0.01) was higher in women than in men. Men and women were of similar age (median 32 vs 29 Years; P=0.2) and a similar number had gonadal/sexual dysfunction (85 vs 83%, P=0.6); weight gain (70 vs 46%; P=<0.0001) and galactorrhea (52 vs 19%; P=<0.0001) were more common in women. Prolactin levels were higher in men than in women, whether exhibiting macro- (2848+/-2954 vs 1132+/-2351 microg/l, P=<0.0001) or microadenomas (187.8+/-51.8 vs 135.4+/-60.5 microg/l, P=0.009) and the size of the adenoma was larger in men than in women irrespective of macro- (25.8+/-12.4 vs 17.2+/-7.2 mm, P=<0.0001) or microadenoma diagnosis (8.0+/-1.4 vs 7.1+/-1.6 mm, P=0.04). After treatment, prolactin levels decreased by 89.2-96.4% in all groups, and normalized more frequently in micro- than in macroadenoma patients (86 vs 64%, P<0.0001), regardless of gender (70% vs 69%, P=0.9). Menses resumed in 82% of women, libido disturbances improved in 57% of men. Tumor size was reduced by 45+/-25% and 52+/-24% in macroprolactinoma patients and by 44+/-31 and 38+/-29% in microprolactinoma patients in women and men respectively. Visual field defects disappeared in 61% of women and in 71% of men (P=0.6). CONCLUSIONS: Prevalence of macroprolactinomas was similar in men and women; microprolactinomas and non-tumoral hyperprolactinemia were more frequent in women. Clinical symptoms at presentation differed according to gender, with galactorrhea and weight gain more frequent in women. The successful response to cabergoline treatment for 6 Months was higher in micro- than in macroprolactinoma patients and was similar in women and men.

We report the results of a prospective Italian multi-center study of the effects of lanreotide, a slow-release somatostatin analog, on left ventricular morphology and function and on the prevalence of ventricular arrhythmic events in 19 patients with active, newly diagnosed, uncomplicated acromegaly. Cardiac features were evaluated with Doppler-echocardiography and 24-h Holter ECG monitoring at baseline and after 6 months of lanreotide therapy. Fifteen patients (78.9%) had left ventricular hypertrophy. Lanreotide treatment significantly decreased the left ventricular mass (127.8±6.9 vs 140.7±7.1 g/m2, p<0.001) and left ventricular hypertrophy significantly disappeared in 6 of these patients. Treatment did not significantly affect systolic function, whereas it increased the Doppler- derived early-to-late mitral flow velocity, (E/A) ratio, of early-to-late trans-mitral flow velocity (1.34±0.1 vs 1.09±0.06, p=0.001). Stroke volume was slightly but not significantly increased after treatment, whereas systolic BP was significantly higher (134±14 vs 129±13 mmHg, p<0.05). The 24-h mean heart rate was significantly reduced after treatment (66.5±11 vs 71.5±20 beats/min, p<0.05). Supra-ventricular premature beats (>50/24 h) occurred in 16.6% of patients and were unaffected by treatment. Differently, ventricular premature beats (>50/24 h) occurred in 33.3% of patients before treatment vs 16.5%, after treatment. In conclusion, lanreotide reduced the left ventricular mass, and improved ventricular filling and ventricular arrhythmic profile. (J.

Despite the observation that parity may increase the risk of thyroid carcinoma, very few studies have investigated the possible repercussion of parity on thyroid benign pathology. Recently, parity has been identified as one of the factors contributing to a larger thyroid size in healthy females. The aim of this work was to investigate a possible role for parity on the prevalence of multinodular goiter in iodine deficient areas. For this purpose, the reproductive histories of 2 cohorts of women, normal (Group I, 235 cases) and non-toxic multinodular goiter (NTMNG) affected (Group II, 274 cases) were compared. All subjects were euthyroid and had no previous history of thyroid function abnormalities. The number of full-term previous pregnancies (2.55±0.11 vs1.77±0.10) and age (47.7±0.76 vs42.3±0.83 yr) were found significantly higher (p<0.001) in multinodular goiter (MNG) patients than controls. Parity and age were found to be directly correlated (p<0.001), nevertheless the partial correlation coefficients demonstrated an independent and statistically significant difference for both variables between normal and NTMNG. Therefore, the independent effects of parity and age were further investigated. The effect of age on NTMNG prevalence seems to be weaker, in fact significant differences (p«0.001) for age between patients and controls were detected only when the effect of parity was absent (nulliparous), while with increasing gestations the effect of age disappeared. Our results indicate that age plays a minor role compared to parity which can therefore be considered as a stronger risk factor. In conclusion, the present study shows that, at least in iodine deficient regions, non-toxic multinodular goiter women show a statistically significant higher parity rate than healthy controls. Age may play a certain role but only when additional stronger risk factors are absent.

Interferon (IFN)-ß has become a widespread therapy for multiple sclerosis. As already reported for IFN-a, thyroid autoimmunity and dysfunctions have been observed also in course of IFN-ß therapy. Nevertheless, very few cases of Graves’ disease, occurred in such condition, have been reported in literature. We here describe the case of a 40-year-old female affected by multiple sclerosis, who received IFN-ß-1b, 8 million IU sc every other day for her condition. After 22 months of cytokine administration, she developed a severe Graves’ disease with persistently positive TRAb which suggested the withdrawal of the treatment. Our patient had performed a complete thyroid evaluation with normal findings, before and during the first 6 months of therapy. This case suggests that patients undergoing long-term IFN-ß therapy should be monitored for thyroid hormones and antibodies throughout the treatment as thyroidal side effect can be a late event.

Abstract: In order to investigate the antiproliferative properties of antamanide, we have synthesized and studied two antamanide analogs where the phenylalanine residue in positions 6 or 9 is substituted by tyrosine, their corresponding linear forms and the cyclic and linear des Phe⁵,Phe⁶-Tyr⁹-analogs. Antamanide and its biologically active synthetic analogs are able to form highly stable complexes with metal ions, particularly Na⁺, K⁺ and Ca²⁺. We studied the ion-binding properties of the Tyr-antamanide analogs by CD and Tb³⁺-mediated fluorescence in acetonitrile. In this medium the far-and near-UV CD spectra of the neat Tyr⁶-antamanide analog are very similar to that of the parent cyclic decapeptide. Substantial differences occur on the contrary in the CD spectra of the neat Tyr⁹-antamanide, particularly in the regions at 220 nm and 270-290 nm. In acetonitrile, as already found for antamanide, the interaction with the above-mentioned metal ions always produces evident changes in the far- and near-UV CD spectra of both analogs. On the contrary, the CD spectra of the linear deca- and octa- and of the cyclic octa-analogs are affected by the presence of metal ions only in the near-UV region. In the same solvent the Tb³⁺-mediated fluorescence spectra of all the synthetic peptides are remarkably affected by the addition of ions. On the basis of the spectral total changes, by using either or both the spectroscopic techniques, it has been possible to determine the ion binding constants for all the linear and cyclic Tyr-antamanide analogs and to compare them with that of the parent peptide. The antitoxic and antiproliferative activities of these antamanide analogs have been tentatively correlated to their ion-binding properties. A preliminary account of this work was given in ( 1).

Thyroid autoimmunity and dysfunction are a well known side effect of IFN α therapy for viral hepatitis and tumors, while the IFN β effects on the thyroid gland in neurological patients have not been studied. The aim of this longitudinal study was to look for the appearance of thyroid autoimmunity as well as for the occurrence of overt thyroid disease in the patients affected by multiple sclerosis (MS) treated with IFN β 1b. Eight patients (4 males, 4 females) undergoing r-IFN β 1b treatment (8 M.U. every other day for 9 months) for relapsing remitting multiple sclerosis entered the study. We have analyzed thyroid function parameters and auto antibody levels before and after 1, 2, 3, 6 and 9 months of therapy. None of them referred to familiar thyroid pathology or presented clinically overt thyroid disease except for one patient (case 4) who showed TPO-Ab pretreatment positivity and another (case 8) who was in therapy with Levothy-roxine 100 μg/die for multinodular goiter. The number of patients with appearance of thyroid antibodies has slowly increased, until the third month of therapy with 3 patients out of 7 positive for TPO-Ab. The only case of overt thyroid dysfunction reported by us appeared after nine months of therapy and consisted of a hypothyroidism. Our data suggest that short-term interferon β treatment is able to induce thyroid autoimmunity (42.8%) and dysfunction (12.5%).

Lithium carbonate, widely used in the treatment of bipolar patients, is well known to induce thyroid alterations. In this longitudinal study the thyroid function was investigated during lithium treatment over a period of 12 months in 12 euthymic bipolar patients with a normal thyroid function and absence of thyroid antibodies. Nine of the 12 patients were further studied on the 15th month, 5 of these 9 on the 18th month and 4 of the last-mentioned 5 on the 24th month. The mean basal and TRH-stimulated TSH values during lithium therapy were significantly higher as compared to those at the beginning of the treatment. More particularly, during lithium therapy, a significant increase of basal TSH over the normal range was found in 10 out of the 12 patients. A rise of TRH-stimulated TSH was found in 11 out of the 12 patients. The impairment of the hypothalamic-pituitary-thyroid (HPT) axis was transitory in the majority of cases. Two patients developed a nodular goiter during the treatment. Plasma T3, T4, FT3 and FT4 levels did not change during the treatment. Thyroid antibodies remained undetectable. The conclusions of the study are twofold: 1) Subclinical hypothyroidism during lithium therapy is much more frequent than previous cross-sectional studies suggest; 2) Thyroxine replacement in lithium-treated patients is advisable in order to prevent subclinical hypothyroidism and the risk of a subsequent goiter.

We have studied a young untreated patient with low-renin hypertension. All the clinical tests were in normal range, except plasma renin activity, which was low. Also all traditional tests evaluating the adrenal function were normal. A test of supraphysiological ACTH stimulation revealed a partial enzymatic defect of adrenal 11-hydroxylase. The patient has been treated with dexamethasone (0.75 mg once daily), during 4 weeks. At the end of the treatment blood pressure reached normal values. The traditional adrenal function tests are not sufficient to exclude enzymatic abnormalities and their possible involvement in the pathogenesis of hypertension.