Changes in quality of life after thyroidectomy in subjects with thyroid cancer in relation to the dose of levothyroxine.

PURPOSE: Previous studies demonstrated decreased quality of life (QoL) in differentiated thyroid cancer (DTC) survivors and suggested QoL variability related to time from thyroidectomy and levothyroxine dosage. The aims of this study were to evaluate QoL in thyroidectomized subjects in different levothyroxine states and to evaluate the association between TSH and thyroid hormones and QoL. METHODS: Prospective 5-year study enrolling 208 patients thyroidectomized for DTC, studied in one to four times according to levothyroxine dosage: withdrawal (WITHD), complete (C-SUPP) and mild TSH-suppression (M-SUPP), replacement (REPL). Each patient was allowed to participate into the study more than one time. A total of 300 evaluations were collected, consisting of detailed thyroid hormone profile and QoL assessment through the ThyPRO questionnaire. RESULTS: Comparing the four groups, significant differences were found for anxiety, impaired social and daily life and item 12 (overall impact of thyroid disease) domains (p < 0.05). Interestingly, C-SUPP subjects reported the best scores in almost all ThyPRO scales. Significant correlations were found between QoL and pituitary-thyroid axis function, as well as between QoL and gender, being females more affected. At multiple regression analyses fT3 demonstrated to be the best explanatory factor for overall impact of thyroid disease on the patient's life, followed by gender. CONCLUSIONS: TSH-suppressive doses of levothyroxine are more effective in improving QoL in DTC patients after thyroidectomy. These results confirm the urgent need of further studies aimed to define the best treatment of hypothyroidism, effective on well-being and harmless for patients.

Hepatitis C virus long-term persistence in peripheral blood mononuclear cells in patients with haemophilia. Detection of occult genotype 1.

Peripheral blood mononuclear cells (PBMC) from chronic hepatitis C virus-infected persons can harbour viral variants that are not detected in plasma samples. We explored the presence and persistence of HCV genotypes in plasma and PBMC cultures from 25 HCV-monoinfected and 25 HIV/HCV-coinfected patients with haemophilia. Cell cultures were performed at different time points between 1993 and 2010-2011, and the HCV genome was examined in culture supernatants. Sequential plasma samples were studied during the same time period. Analysing sequential plasma samples, 21% of patients had mixed-genotype infections, while 50% had mixed infections determined from PBMC culture supernatants. HIV coinfection was significantly associated with the presence of mixed infections (OR = 4.57, P = 0.02; 95% CI = 1.38-15.1). In our previous study, genotype 1 was found in 72% of 288 patients of this cohort. Similar results were obtained with the sequential plasma samples included in this study, 69% had genotype 1. However, when taking into account plasma samples and the results from PBMC supernatants, genotype 1 was identified in 94% of the population. The PBMC-associated variants persisted for 10 years in some subjects, emphasizing their role as long-term reservoirs. The presence of genotype 1 in PBMC may be associated with therapeutic failure and should not be disregarded when treating haemophilic patients who have been infected by contaminated factor concentrates. The clinical implications of persistent lymphotropic HCV variants deserve further examination among multiple exposed groups of HCV-infected patients.

Intra-host evolution of multiple genotypes of hepatitis C virus in a chronically infected patient with HIV along a 13-year follow-up period.

The intra-host evolutionary process of hepatitis C virus (HCV) was analyzed by phylogenetic and coalescent methodologies in a patient co-infected with HCV-1a, HCV-2a, HCV-3a and human immunodeficiency virus (HIV) along a 13-year period. Direct sequence analysis of the E2 and NS5A regions showed diverse evolutionary dynamics, in agreement with different relationships between these regions and the host factors. The Bayesian Skyline Plot analyses of the E2 sequences (cloned) yielded different intra-host evolutionary patterns for each genotype: a steady state of a "consensus" sequence for HCV-1a; a pattern of lineage splitting and extinction for HCV-2a; and a two-phase (drift/diversification) process for HCV-3a. Each genotype evolving in the same patient and at the same time presents a different pattern apparently modulated by the immune pressure of the host. This study provides useful information for the management of co-infected patients and provides insights into the mechanisms behind the intra-host evolution of HCV.

Search for light dark matter in XENON10 data.

We report results of a search for light (≲10 GeV) particle dark matter with the XENON10 detector. The event trigger was sensitive to a single electron, with the analysis threshold of 5 electrons corresponding to 1.4 keV nuclear recoil energy. Considering spin-independent dark matter-nucleon scattering, we exclude cross sections σ(n)>7×10(-42) cm(2), for a dark matter particle mass m(χ)=7 GeV. We find that our data strongly constrain recent elastic dark matter interpretations of excess low-energy events observed by CoGeNT and CRESST-II, as well as the DAMA annual modulation signal.

Limits on spin-dependent WIMP-nucleon cross sections from the XENON10 experiment.

XENON10 is an experiment to directly detect weakly interacting massive particles (WIMPs), which may comprise the bulk of the nonbaryonic dark matter in our Universe. We report new results for spin-dependent WIMP-nucleon interactions with 129Xe and 131Xe from 58.6 live days of operation at the Laboratori Nazionali del Gran Sasso. Based on the nonobservation of a WIMP signal in 5.4 kg of fiducial liquid xenon mass, we exclude previously unexplored regions in the theoretically allowed parameter space for neutralinos. We also exclude a heavy Majorana neutrino with a mass in the range of approximately 10 GeV/c2-2 TeV/c2 as a dark matter candidate under standard assumptions for its density and distribution in the galactic halo.

First results from the XENON10 dark matter experiment at the Gran Sasso National Laboratory.

The XENON10 experiment at the Gran Sasso National Laboratory uses a 15 kg xenon dual phase time projection chamber to search for dark matter weakly interacting massive particles (WIMPs). The detector measures simultaneously the scintillation and the ionization produced by radiation in pure liquid xenon to discriminate signal from background down to 4.5 keV nuclear-recoil energy. A blind analysis of 58.6 live days of data, acquired between October 6, 2006, and February 14, 2007, and using a fiducial mass of 5.4 kg, excludes previously unexplored parameter space, setting a new 90% C.L. upper limit for the WIMP-nucleon spin-independent cross section of 8.8x10(-44) cm2 for a WIMP mass of 100 GeV/c2, and 4.5x10(-44) cm2 for a WIMP mass of 30 GeV/c2. This result further constrains predictions of supersymmetric models.

Exclusión de paternidad con 14 STR en provincia de Buenos Aires. Argentina / Paternity eclusions with 14 STRs in Buenos Aires province

Sobre un total de 546 estudios de filiación analizados por electroforesis capilar utilizando los kits PowerPlex 16 o Identifiler, se registraron exclusiones en 103 casos (18,9 por ciento). De estos, se analizaron en forma detallada 69 informes. El número promedio de marcadores que excluyeron el vínculo fue de 8. En el 50 por ciento de los casos se detectaron de 6 a 8 exclusiones. En un único análisis el número de exclusiones fue de 3. El marcador que puso en evidencia el mayor número de incompatibilidades fue el FGA y el locus que resultó menos informativo el TPOX (AU)

Inclusión de paternidad con 14 STR en provincia de Buenos Aires, Argentina / Paternity inclusions with 14 STRs in Buenos Aires province

Se realizaron 546 estudios de filiación por electroforesis capilar utilizando los kits PowerPlex e Identifiler; con un promedio de 14 marcadores STR analizados. El 75,5 por ciento de los casos fueron inclusiones, el 18,9 por ciento fueron exclusiones y el 1,6 por ciento resultó no informativo. El 4 por ciento restante correspondió a impugnaciones y reconocimiento de paternidad (dos padres alegados).Sobre 211 inclusiones (madre, hijo, padre alegado) el 95,3 por ciento resultó con índice de paternidad superiores a 104. En 40 inclusiones hijo/padre o madre alegados el 80 por ciento de los índices estimados resultó mayor de 104. En 9 casos se consideró la presencia de una mutación en el hijo (AU)

Delitos sexuales: relevamiento de las solicitudes de cotejo durante el 2001 / Sexual offenses: relevance of comparison requests for 2001

El Laboratorio de Inmunogenética es un organismo dependiente de la Suprema Corte de Justicia de la provincia de Buenos Aires. Durante el año 2001 ingresaron 295 pedidos de delitos sexuales, abarcando violaciones (41,4 por ciento), violaciones agravadas (18,7 por ciento), violaciones seguidas de muerte (2,2 por ciento), abuso sexual (28,4 por ciento), abuso deshonesto (7,2 por ciento) y estupro (2,1 por ciento). En un 22 por ciento las víctimas fueron menores. En un 34 por ciento el autor permanece desconocido. En el 45 por ciento del total de los casos analizados, se observó correspondencia entre el genotipo detectado en las evidencias y el imputado, mientras que un 20 por ciento resultaron exclusiones. Como conclusión del relevamiento surge la necesidad de implementar una base de datos (AU)

Solvation enthalpies as descriptors of structure--in vitro percutaneous permeation relationship of benzoxazinones regioisomers.

The aim of this work was to correlate the in vitro human skin permeability, expressed as the permeability coefficient (Kp), and some physicochemical parameters of a new series of benzoxazinones. The in vitro human skin permeability of 14 substances, including regioisomers with CH3, OH, OCH3, and Cl groups in different positions on the aromatic ring, was determined. The modified Franz diffusion cell method was used. The Kp values were in the range 0.14-8.24 cm/h, showing a strong dependence on the position and type of substituent. Physicochemical descriptors usually referred in literature, such as log P, molecular weight and volume (MV), hydrogen bond donor (Hd) and acceptor activity (Ha), and molecular refractivity were considered, with the addition of solvation enthalpy (delta deltaHsolv). Delta deltaHsolv is defined as the difference between formation enthalpies in water and octanol. The algorithm with the best correlation between Kp and physicochemical descriptors was calculated, taking into account the differences observed among the regioisomers. The algorithm obtained with delta deltaHsolv had a good correlation (r2 = 0.749, F = 16.43, P = 0.0005), comparable with the equation, proposed by Potts and Guy, based on MV, Hd and Ha (r2 = 0.830, F = 16.3, P = 0.0004).

Pharmacokinetics of ITF 296 (Sinitrodil) a novel organic nitrate, in healthy volunteers.

ITF 296 is a new orally active nitrate acting selectively on large arterial vessels over a wide range of doses. In healthy volunteers it causes less reduction in vascular resistance and less venodilatation than classic nitrates. Its pharmacokinetic profile was evaluated after intravenous infusion and oral (solution and immediate-release tablet) administration in a randomised cross-over design on 11 healthy volunteers. The plasma levels of ITF 296 and its metabolite ITF 1124 were determined by a HPLC method. The drug is rapidly distributed (mean steady-state distribution volume 53+/-17 liters) and eliminated (half-life of about 25 minutes) both after intravenous and oral administration. The total clearance is 2. 31+/-0.46 l/min. The oral solution of ITF 296 is well absorbed (Cmax=0.057 microg/ml, tmax=30 min) but it undergoes a first-pass effect (F=25%). The tablet, developed only for Phase 1 clinical studies, is characterised by an immediate release (Cmax=0.057 microg/ml, tmax=30 min). The extent of its absolute and relative bioavailability is about 14% and 53% respectively.

In vitro skin permeation of Sinitrodil, a member of a new class of nitrovasodilator drugs.

Clinical trials have shown the potential of benzoxazinones, a new class of organic nitrates, in cardiovascular therapy. In particular Sinitrodil possesses a coronary vascular selectivity greater than that of Nitroglycerin and isosorbide dinitrate. The objective of this study was a preliminary evaluation of the ability of these new organic nitrate derivatives to reach therapeutical steady-state plasma concentrations following a transdermal administration. In vitro permeation studies through human stratum corneum and epidermis have been conducted on two members of this class: Sinitrodil (ITF 296) and ITF 1129. Comparative studies have also been carried out with Nitroglycerin, Isosorbide dinitrate and Nicorandil. Two different fixed concentrations were tested: 0.08% w/v solution and saturated solution. Sinitrodil could be considered a good candidate for transdermal administration on the basis of the in vitro permeation results and of the known therapeutical plasma concentration.

Pharmacokinetic study in rats after single intravenous and oral administrations of [14C]-ITF-296.

Pharmacokinetics of [14C]-ITF-296 and its metabolites, ITF-1124 and ITF-1577, were studied in rats after a single intravenous (2.5 mg/kg) and oral (10 mg/kg) administration. Radioactivity was measured by LSC while unchanged drug and its metabolites in plasma were assayed by an HPLC-UV method. The absorption of [14C]-ITF-296 after oral administration is practically complete. Elimination of radioactivity occurs mainly in urine (higher than 80%) and the recovery of the dose (higher than 95%) takes place up to 96 h after both treatments. Both by i.v. and p.o. route the results show that the radioactivity is largely excreted in the bile and reabsorbed in the intestine. The tissue distribution study indicates that there is no accumulation or localization of radioactivity in the major organs or blood and no radioactivity levels are found 96 h after either treatment. In addition, whole body autoradiography confirms the tissue distribution pattern, showing no differences between albino and pigmented rats.

Pharmacokinetic study in dogs and monkeys after single intravenous and oral administrations of [14C]-ITF-296.

Pharmacokinetics of [14C]-ITF-296 and its metabolites, ITF-1124 and ITF-1577, were studied in dogs and monkeys after a single intravenous (2.5 mg/kg) and oral (10 mg/kg) administration. Radioactivity was measured by LSC while unchanged drug and its metabolites in plasma were assayed by an HPLC-UV method. The absorption of [14C]-ITF-296 after oral administration is practically complete both in dogs and in monkeys. The determination of unchanged drug and its metabolites shows quite a similar profile in dogs and monkeys for ITF-296 and ITF-1124 and a different time-course for ITF-1577. Elimination of radioactivity occurs mainly in urine (namely 70-80%) for both species and the recovery of the dose (higher than 90%) takes place up to 96 h after both treatments.

Simultaneous determination of ITF 296 and two metabolites in plasma by a validated HPLC method.

A simple and sensitive HPLC validated method was developed for the simultaneous determination of ITF 296 (a new orally active nitrate) and its metabolites ITF 1124 and ITF 1577 in biological samples. Quantitation was performed by peak height ratios between the three compounds and the internal standard (ITF 1721). Detection limit of the method was 0.005 microgram/ml using 1 ml of plasma. The results indicated that the method is reproducible, accurate, precise, sensitive and specific for the measurement of the three compounds in plasma samples. Those characteristics allowed us to conclude that the method is suitable for analysing samples obtained after administration of ITF 296 to humans at therapeutic dosage and to animals for formulation studies.

HPLC determination of ITF 188 and its metabolite ITF 1078 in urine after intranasal administration of new heparin salt ITF 1300 to dogs.

Heparin salt ITF 1300 in which low molecular weight heparin is salified with a new counterion, di-[3-(N,N-dibutylamino)]propyl carbonate (ITF 188), was selected for the pharmacological development. A specific, sensitive and reproducible HPLC method for the determination of ITF 188 and its alcoholic metabolite ITF 1078 in urine was developed. The method was employed for the study of urinary excretion of the counterion after intranasal administration of ITF 1300 to dogs. The total amount of ITF 188 and ITF 1078 found in urine within 72 hours after the nasal instillation of ITF 1300 accounts for about 5% of the administered dose.

Flexible electrogoniometers: kinesiological advantages with respect to potentiometric goniometers.

Unlike conventional potentiometric goniometers, flexible electrogoniometers do not suffer from any alignment problems with respect to the joint axis. We hypothesized that flexible goniometers provide more valid measurements in that they avoid some biomechanical pitfalls. With both devices simultaneously we measured the movements of dorsal flexion of the ankle and flexion of the knee in three healthy subjects. In the various subjects, this comparison showed that the flexible goniometers signalled ankle excursion greater by 19-40% with the foot remaining in neutral position or being simultaneously pronated, and lower by 10-21% with the foot being simultaneously supinated. At the knee the flexible goniometers signalled a flexion greater by 24-32%, with respect to potentiometric goniometers. Biomechanical considerations support the validity of records taken with flexible goniometers, potentiometric measures being biased by (a) multijoint, multiplane motions underlying foot dorsal flexion, and (b) multiaxis motion underlying knee flexion RELEVANCE: In measurements of angles between adjacent body segments, flexible goniometers should be preferred to potentiometric goniometers despite their higher cost. Flexible goniometers not only are more practical: more importantly, they provide a valid measure of relative orientations in one plane, regardless of the number and different concurrent motions of the underlying joints.

[Effect of GH/IGF-I deficiency on bone and collagen turnover in children and adults with GH deficiency]. / Effetti della carenza di GH/IGF-I sul turnover osseo e collagene in bambini ed adulti con deficit di GH.

Serum bone Gla protein (BGP), marker of osteoblastic function, carboxyterminal cross-linked telopeptide of type I collagen (ICTP), index of bone resorption, and aminoterminal propeptide of type III procollagen, marker of collagen synthesis, were evaluated in children with GH deficiency (GHD), in adults with childhood-onset GHD and in adults with acquired GHD in adultlife. In children with GHD, serum BGP (12.7 +/- 0.5 ng/ml), ICTP (8.5 +/- 0.9 ng/ml) and PIIINP (3.4 +/- 0.4 ng/ml) were significantly lower (p < 0.0001, p < 0.0001 and p < 0.001, respectively) than those observed in a sex and age matched control group (BGP:18.9 +/- 0.9 ng/ml, ICTP: 14.4 +/- 0.6 ng/ml, PIIINP: 6.7 +/- 0.7 ng/ml). In adults with childhood onsed GHD, BGP levels (3.7 +/- 0.4 ng/ml) were significantly lower (p < 0.0001) than those recorded in a sex and age matched control group (5.4 +/- 0.1 ng/ml), while ICTP (4.7 +/- 0.7 ng/ml) and PIIINP (3.7 +/- 0.5 ng/ml) levels were similar to those found in controls (ICTP: 4.1 +/- 0.3 ng/ml; PIIINP: 3.3 +/- 0.2 ng/ml). In adults with acquired GHD, serum BGP (5.3 +/- 0.4 ng/ml), ICTP (3.8 +/- 0.4 ng/ml) and PIIINP (3.6 +/- 0.3 ng/ml) levels were not significantly different from those recorded in controls (BGP: 5.4 +/- 0.1 ng/ml, ICTP: 4.1 +/- 0.3 ng/ml, PIIINP: 3.3 +/- 0.2 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)