bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of boron concentration and grain size on weld heat affected zone microfissuring in Inconel 718 base superalloys
Authors: Guo H. , Chaturvedi M.C. , Richards N.L.
Published: June 2004

Microfissuring in the heat affected zone (HAZ) around electron beam (EB) welds was studied in two Inconel 718 based superalloys containing the minimum possible concentrations of C, S and P, and 11 and 43 wt-ppm concentrations of B. The microfissuring susceptibility was evaluated by measuring the microcracks formed in the HAZs of EB welds and by examining the hot ductility behaviour of the material. Bead on plate type EB welding, and on cooling hot ductility tests in a Gleeble 1500 thermomechanical simulator were performed on the two alloys with different grain sizes. The results of the hot ductility tests and crack measurements on EB welded samples correlated very well with each other. Using both techniques it was observed that the HAZ microfissuring of Inconel 718 increased with an increase in B concentration and an increase in grain size. The effect of B was attributed to its segregation to the grain boundaries, which resulted in a reduction in the melting point of the grain boundary material. This rendered them susceptible to liquation in the HAZ, and formation of microfissures due to the introduction of stresses during the cooling portion of the welding thermal cycle.
Prediction of nugget development during resistance spot welding using coupled thermal–electrical–mechanical model
Authors: Khan J. A. , Xu L. , Chao Y.-J.
Published: June 2004

An axisymmetric finite element model employing coupled thermal–electrical–mechanical analysis of resistance spot welding is presented. The welding parameters considered include: heat generation at the faying surface and the workpiece–electrode surface; Joule heating at the workpiece and the electrode; and the thermal contact conductance between the electrode and the workpiece. The latent heat of phase change due to melting is accounted for. The effect of friction coefficient on the workpiece interface is also studied. The computed results agree well with the experimental data. Heat generation at the faying surface in the initial stages of welding dominates the nugget development, and Joule heating at long times governs the weld nugget growth. A parametric study is carried out for the nugget growth with specific consideration of resistance spot welding of Al alloys. Process control and modelling of resistance spot welding of Al alloys is more difficult than that for steel because of their high electrical and thermal conductivity and low melting point.
Monitoring indices for assessing pulsed gas metal arc welding process
Authors: Ogunbiyi B. , Nixon J. , Richardson I. , Blackman S.
Published: June 2004

A methodology is presented for monitoring the pulsed gas metal arc welding process objectively using indices calculated from the statistical features of the welding current and voltage transient waveforms. Five monitoring indices are presented. The indices allow the quantitative interpretation of process performance and give an indication of which process parameter(s) should be altered to ensure stable pulse welding performance.
Use of acoustic emission to detect reheat cracks during post-weld heat treatment
Authors: Ferraresi V.A. , Modenesi P.J. , Mastelari N. , da Exaltação Trevisan R.
Published: June 2004

The phenomenon of stress relief cracking or reheat cracking can occur in the heat affected zone (HAZ) of welded joints during post-weld heat treatment (PWHT). The coarse grained region, which results from heating at elevated temperatures in the austenitic region, is the most susceptible to this problem. The present research programme was aimed at determining, by means of an acoustic emission measurement system (AEMS), the instant of propagation of reheat cracks during PWHT. The AEMS was fixed to a modified implant test device that allowed the loading of a specimen subjected to thermal cycles similar to those typically experienced by welded components in stress relief treatments. Tests were carried out with this setup using different load levels for the same thermal cycle and welding condition. Welding was done by means of the metal active gas process. The study was developed using a high strength low alloy (HSLA) steel commercially produced in Brazil. Test results have shown that the AEMS is adequate for monitoring the formation and growth of reheat cracking during PWHT.
Prediction of penetration depths during electron beam welding
Authors: Hemmer H. , Grong Ø.
Published: June 2004

An analytical penetration model for electron beam welding is presented, based on a combination of the moving line source solution and the solution for a cylindrical cavity moving through a plate of finite thickness. The input parameters are the net beam power, welding speed, keyhole wall temperature, and diameter of the electron beam from which the penetration depth can be calculated for a range of base materials, such as stainless steels, titanium grade 2, and aluminium alloy AA 5052. It is concluded that the penetration model is sufficiently comprehensive and relevant to be used as a predictive tool in ordinary production welding and some possible applications are briefly outlined.
Optimisation of Nd–YAG laser welding of superduplex stainless steel by parameter design
Authors: Yip W.M. , Man H.C. , Ip W.H.
Published: June 2004

Many researchers have found the welding of super duplex stainless steel UNS S32760 (Zeron 100) by high power CO2 laser to be an unacceptable process, because the austenite/ferrite (γ/α) ratio in the laser weld bead normally deviates significantly from the optimum balance of 50 : 50. To date, the best γ/αratio in a laser weld reported in the published literature was ∼30 : 70. The high percentage of ferrite would result in lower strength and poor corrosion properties. The present investigation was aimed at achieving a near 50 : 50 γ/αratio laser weld using the Nd–YAG laser. These lasers have more process parameters that can be varied, compared to CO2 lasers. Three different kinds of output power waveform, continuous, sine, and square waves, together with many other parameters, were investigated. The Taguchi method was used for parameter design, to reduce the number of experiments. Based on the Taguchi approach, optimum process parameters were determined and laser weld beads that consisted of 55 : 45 γ/α were achieved.
Hot ductility behaviour of 18%Ni maraging steel
Authors: Chen M.H. , Chou C.P.
Published: June 2004

The hot ductility behaviour of a material exhibits a good correlation with its heat affected zone (HAZ) hot cracking sensitivity. This study was aimed at evaluating the HAZ hot cracking susceptibility of 18%Ni maraging steel and exploring the relationship between hot ductility and microstructure of the HAZ in an 18%Ni maraging steel. Optical metallography and scanning electron microscopy (SEM) investigations revealed that the ductility loss was accompanied by fracture transition from ductile transgranular mode to brittle intergranular mode. Fracture specimens were examined using SEM with an attached energy dispersive X-ray spectrometer. The SEM fractographs indicate that the ductile transgranular dimple fracture (i.e. coarse) surface was the titanium rich inclusion precipitated at the grain boundary, which promotes microvoid nucleation, growth, and coalescence and leads to localisation deformation until final fracture. Results of hot ductility tests also indicate that the titanium rich inclusion can reduce the ultimate tensile strength without reducing the tensile ductility. The appearance of brittle intergranular fracture is caused by the constitutional liquation of titanium sulphide inclusions that induces formation of a liquid film penetrating the grain boundaries. The results show that titanium sulphide inclusion not only reduces the HAZ tensile ductility, but also reduces the ultimate tensile strength.
Model for inclusion formation in low alloy steel welds
Authors: Babu S.S. , David S.A. , Vitek J.M. , Mundra K. , DebRoy T.
Published: June 2004

Oxide inclusion formation in low alloy steel welds is described with a model as a function of weld metal composition and process parameters. The model was developed by coupling thermodynamic and kinetic considerations. Thermodynamic calculations considered the effect of the alloying elements and kinetic equations allowed, describing oxide formation during weld cooling. The model showed that weld cooling rate influences the inclusion characteristics and therefore must be taken into consideration. This inclusion model is capable of predicting the composition, size, number density, and oxidation sequence of inclusions and was verified with published data. The inclusion model was coupled with numerical heat transfer and fluid flow models to extend the model to a wide range of welding process conditions.
Model for estimating electrode face diameter during resistance spot welding
Authors: Lu F. , Dong P.
Published: June 2004

A mathematical model has been constructed to predict the electrode face diameter at various stages of electrode life. The model relates the electrode face evolution process to electrode design and welding parameters such as welding current, electrode force, etc. It requires a minimum amount of experimental data to determine the numerical constant in the model, which characterises electrode wear rate. To validate the model, constant welding current electrode life test data were used. These data were derived from earlier electrode life tests on six different galvannealed steels. The electrode face diameter was continuously recorded by carbon imprint tests at 200 weld intervals throughout the life tests. Excellent agreement between the experimental results and the model predictions has been achieved. Potential applications of the model in selecting electrode design and optimising welding schedules are also discussed.
Keyhole bottom separation in two beam Nd–YAG laser welding
Authors: Narikiyo T. , Miura H. , Fujinaga S. , Takenaka H. , Ohmori A. , Inoue K.
Published: June 2004

A pair of Nd–YAG laser beams transmitted through optical fibres from two oscillators have been condensed separately and combined at a single point on the workpiece in order to enhance welding ability. Bead on plate tests were carried out with symmetric arrangements of condensing optics in two different welding directions. Transition from penetration with one keyhole bottom to penetration with two bottoms occurred as the laser power increased when the angles of incidence of the laser beams were 30 or 45°. No transition occurred at 15°. Melting efficiency increased dramatically at the transition power, the transition conditions being determined by laser power and heat input.
Hybrid welding with arc and laser beam
Authors: Tusek J. , Suban M.
Published: June 2004

This paper deals with a combination of two different welding processes, i.e. the synergic action of two different heat sources for fusion welding. The major part of the paper is focused on the combined action of a welding arc and a laser beam. The main advantage of the use of both heat sources is more efficient use of the energy supplied. With certain parameters, the quantity of molten material increases by 100% compared with the sum of the individual quantities of molten material in the individual processes. The paper further presents several practical applications of the combined welding process. Eventually, development of arc augmented laser welding may progress in two directions; the first being the synergic effect of a laser beam and plasma welding arc and the second the combination of tandem laser welding and consumable electrode welding. This paper presents two such cases schematically.
Pseudorandom noise injection as diagnostic tool for gas metal arc welding systems
Authors: Lin Q. , Simpson S.W. , Offerman S.E. , Rados M.
Published: June 2004

The present work reports results obtained by applying pseudorandom noise injection to the gas metal arc welding process to determine the impulse response of the system (the response to a short pulse of energy). The phenomena having the longest time constants are investigated and it is found that there is a damped oscillation associated with delayed heating of the anode wire stickout. Properties of the oscillation are measured and found to agree with previous research. It is demonstrated that the pseudorandom noise injection technique has advantages in investigating welding processes in which it is desired to determine operating characteristics without significantly perturbing welding.
Characterisation of electron beam welded aluminium alloys
Authors: Çam G. , Ventzke V. , Dos Santos J.F. , Koçak M. , Jennequin G. , Gonthier-Maurin P.
Published: June 2004

Electron beam (EB) welding was performed on three different aluminium alloys, namely alloys 2024, 5005, and 6061 (plate thickness 5 mm except alloy 5005 which was 3 mm in thickness), to establish the local microstructure–property relationships that would satisfy the service requirements for an electron beam welded aluminium alloy component with weld zone strength undermatching. Microstructural characterisation of the weld metals was carried out by optical and scanning electron microscopy. A very low level of porosity was observed in all EB welds owing to surface cleaning before welding and the vacuum environment of the EB welding process. Extensive microhardness measurements were also conducted in the weld regions of the joints. Global tensile properties and fracture toughness properties (in terms of crack tip opening displacement, CTOD) of the EB joints were determined at room temperature. The effects of strength mismatch and local microstructure on fracture toughness of the EB joints are discussed. The purpose of the present paper is to report the partial results of the European Brite–Euram project ASPOW (assessment of quality of power beam weld joints; BRPR–CT95–0021), which has been undertaken predominantly by industrial companies to establish a European framework for destructive and non-destructive testing and assessment criteria for laser and electron beam welds of over 20 metallic materials.
Application of neural network to arc sensor
Authors: Eguchi K. , Yamane S. , Sugi H. , Kubota T. , Oshima K.
Published: June 2004

Full penetration control of the weld pool in the first layer of a single side multilayer weldment is important to obtain a good quality weld. For this purpose, a new method, the switchback welding method, is proposed to achieve a stable back bead. A welding torch not only weaves along the groove, but also moves back and forth. Also, a neural network (NN) arc sensor is proposed that estimates the wire extension and the arc length by using measurements of both voltage and current. Moreover, from the output of the NN, the gap and the error (deviation) of the oscillation centre of the torch from the groove centre are estimated. Training data are constructed from experimental results, and performance of the NN arc sensor is examined using test data. Seam tracking is carried out via the output of the NN arc sensors: a good tracking result is obtained.
Additive assisted through the arc sensing during gas tungsten arc welding
Authors: Middel W. , den Ouden G.
Published: June 2004

This paper concerns a novel approach to through the arc position sensing, which is based on the influence that certain additives have on the physical behaviour of the welding arc. The changes in the physical behaviour are reflected by changes in arc parameters, in particular arc voltage, which can be monitored during the welding process. In the first part of the paper the results of bead on plate experiments aimed at determining the influence of different additives on arc voltage are presented. Of the different additives considered, SiO2 is found to have the most pronounced effect. It appears that addition of SiO2 results in a voltage increase in the range 1–3 V, depending on arc length, welding current, and travel speed. The observed effect is ascribed to arc contraction and arc trailing. The influence of SiO2 on the weld bead geometry and the mechanical properties of the weld was also determined. It appears that the addition of SiO2 results in enhanced weld penetration, presumably as a result of the observed arc contraction. The results of hardness measurements carried out on transverse cross-sections of the welds indicate that the mechanical properties of the weld are not significantly affected by the addition of SiO2. Preliminary experiments show that the effect of SiO2 on arc voltage can be used as a tool for position sensing and, hence, for seam tracking during gas tungsten arc (GTA) welding.
Circuit simulation for gas metal arc welding
Authors: Xu P. , Rados M. , Simpson S.W.
Published: June 2004

An electrical circuit was developed to model the behaviour of gas metal arc welding. The model incorporates results from a one-dimensional free burning arc model to describe the arc and a second order differential equation to describe one-dimensional energy conservation in the welding anode. Commercial circuit analy sis software was used to solve the circuit model. Predictions have been compared with experimental data for short circuit transfer mode as well as spray. Predictions agree well with experimental results. The model provides a fast and useful technique to simulate the gas metal arc welding process. In short circuit transfer mode, the model predicts that chaotic phenomena are occurring.
Simulation of rotational arc sensing in gas metal arc welding
Authors: Halmøy E.
Published: June 2004

A mathematical model for the behaviour and interaction of power source, electrode extension, welding arc, and welding joint geometry is applied to simulation of seam tracking signals from high speed rotating electrodes in gas metal arc welding of carbon steel. Sensor signals from a tilted electrode approaching internal and external fillet corners are analysed, as well as the frequency dependence of signal amplitude from a perpendicular electrode. The simulations are compared with experimental results from other references showing good agreement. The current signals are stronger than predicted from static arc characteristics, suggesting important dynamic effects in the behaviour of the electrode extension.
Feasibility of friction stir welding steel
Authors: Thomas W.M. , Threadgill P.L. , Nicholas E.D.
Published: June 2004

The feasibility of friction stir welding (FSW) of steel is demonstrated. Tensile and bend testing have confirmed that the mechanical properties of friction stir welded 12% chromium alloy and low carbon steel joints compare favourably with the properties of the parent metal. Some initial feasibility studies of FSW of both 12% chromium alloy and low carbon steel are described. Although more development work is needed, particularly to improve tool materials, the prognosis for continued developments in FSW of steel is shown to be good.
The Hypothalamic-Pituitary-Thyroid Axis in Preterm Infants; Changes in the First 24 Hours of Postnatal Life
Authors: Murphy Nuala , Hume Robert , van Toor Hans , Matthews Tom G. , Ogston Simon A. , Wu Sing-Yung , Visser Theo J. , Williams Fiona L. R.
Published: June 2004

The purpose of this study was to measure serum T4, free T4, TSH, T3, rT3, T4 sulfate, and thyroxine binding globulin at four time points within the first 24 h of life (cord and 1, 7, and 24 h) in infants between 24 and 34 wk gestation. The infants were subdivided into gestational age groups: 24–27 wk (n = 22); 28–30 wk (n = 26); and 31–34 wk (n = 24). The TSH surge in the first hour of postnatal life was markedly attenuated in infants of 24–27 wk gestation [8 compared with 20 (28–30 wk) and 23 mU/liter (31–34 wk)]. T4 levels in the most immature group declined over the first 24 h, whereas levels increased in the more mature groups [mean cord and 24-h levels: 65 and 59 (NS) vs. 70 and 84 (P < 0.002) vs. 98 and 125 (NS) nmol/liter]. Free T4 and T3 showed only small, transient increases in the most immature group and progressively larger and sustained increases in the other gestational groups. rT3 and T4 sulfate levels in cord serum were higher in the most immature infants, and in all groups levels decreased initially and then variably increased. The features of a severely attenuated or failed hypothalamic-pituitary-thyroid response to delivery critically define this 24- to 27-wk group as distinct from more mature preterm infants.
Menopause Transition: Annual Changes in Serum Hormonal Patterns over the Menstrual Cycle in Women during a Nine-Year Period Prior to Menopause
Authors: Landgren Britt-Marie , Collins Aila , Csemiczky Giorgy , Burger Henry G. , Baksheev Lyrissa , Robertson David M.
Published: June 2004

To examine the hormonal characteristics of menstrual cycles in healthy women approaching menopause, serum hormone profiles were investigated annually in this longitudinal study of 13 healthy women between 4 and 9 yr before menopause and the year of the menopause. Serum FSH, LH, estradiol, progesterone, total inhibin, inhibins A and B, and prolactin were determined in blood samples collected annually three times weekly for 4 wk beginning with the onset of menses. Menstrual bleeding diaries covering this 4- to 9-yr period were also collected allowing the prospective identification of the final menstrual period. A change in serum hormone patterns was observed in cycles approaching menopause, exemplified by an increasing number of cycles of prolonged length with a prolonged follicular phase resulting in a failure to detect a luteal phase rise in serum progesterone within the 4-wk collection period. These prolonged cycles (designated B cycles based on a previous work) were analyzed separately and compared with the remaining ovulatory (D) cycles. No B cycles were identified in any women earlier than 27 cycles from menopause. The proportion of B cycles increased as menopause approached, reaching 62% in the last 10 cycles. The proportion of D cycles decreased accordingly. The B cycles during the initial 4-wk collection period were characterized by elevated FSH, LH, FSH/inhibin A and FSH/inhibin B ratios, and longer duration, although cycle length/subject was not significantly different presumably due to the small number of B cycles. The D cycles showed no changes in hormonal profiles over the 4- to 9-yr time period.

These data indicate that there is a time-related change in the character of menstrual cycles as menopause approaches, with an increasing proportion of cycles observed with prolonged follicular phases that may either be delayed ovulatory cycles or anovulatory cycles. The increase in the proportion of B cycles with elevated early follicular phase FSH levels and low inhibin/FSH ratios toward menopause provides a basis for the apparent early increase in serum FSH and decrease in serum inhibins observed previously in studies of the menopause transition based on sampling confined to the follicular phase only. The data amplify and clarify current concepts of the endocrine basis of the menopause transition.
The Economic Implications of Three Biochemical Screening Algorithms for Pheochromocytoma
Authors: Sawka Anna M. , Gafni Amiram , Thabane Lehana , Young William F.
Published: June 2004

Pheochromocytoma is a rare, life-threatening condition. Using a modeling technique, we studied the economic implications of detection strategies for pheochromocytoma (third-party payer perspective). The diagnostic efficacy of biochemical tests was based on Mayo Clinic Rochester data. In all hypothetical algorithms, positive biochemical tests were followed by abdominal computerized tomography and, if negative, metaiodobenzylguanidine scintigraphy.

In each hypothetical algorithm, imaging would be indicated after positive biochemical testing as follows: algorithm A, fractionated plasma metanephrine measurements above the laboratory reference range; or algorithm B, abnormal measurements of 24-h urinary total metanephrines or catecholamines. In algorithm C, subjects with fractions of plasma metanephrine at or above 0.5 nmol/liter or normetanephrine at or above 1.80 nmol/liter would undergo imaging, whereas those with values between the reference range and these cutoffs would undergo 24-h urinary measurements (total metanephrines and fractionated catecholamines) and be imaged if positive. We determined that, if 100,000 hypertensive patients (including 500 patients with pheochromocytoma) were tested, algorithm A (measurement of fractionated plasma metanephrines alone) would detect 489 pheochromocytoma patients at a cost of 56.6 million dollars, whereas B (24-h urinary measurements) would detect 457 pheochromocytoma patients for 39.5 million dollars, and C (combination of measurements of fractionated plasma metanephrines and urines) would detect 478 patients for 28.6 million dollars. None of the screening strategies for pheochromocytoma described are affordable if implemented on a routine basis in extremely low-risk patients. However, algorithm C may be the least costly, and at a reasonable level of sensitivity, for subjects in whom the suspicion of disease is moderate.
Drospirenone for the Treatment of Hirsute Women with Polycystic Ovary Syndrome: A Clinical, Endocrinological, Metabolic Pilot Study
Authors: Guido M. , Romualdi D. , Giuliani M. , Suriano R. , Selvaggi L. , Apa R. , Lanzone A.
Published: June 2004

The aim of this study was to investigate the effects of the new estro-progestinic containing the antimineralcorticoid progestogen drospirenone (DRSP) in women with polycystic ovary syndrome (PCOS). Fifteen hirsute PCOS patients were treated with 30 μg ethinyl estradiol plus 3 mg DRSP for 12 cycles. Ultrasonographic pelvic exams, evaluation of hirsutism scores, and hormonal and lipid profile assays were performed at baseline and after three, six, and 12 cycles of treatment. An oral glucose tolerance test and euglycemic hyperinsulinemic clamp were also performed, except at the third cycle. The treatment was well tolerated, and all women attained satisfactory cycle control. Hirsutism significantly improved from the sixth cycle onward. Body weight and fat distribution as well as blood pressure remained stable throughout the treatment. Plasma levels of LH, testosterone, SHBG, and, consequently, the free androgen index significantly fell from the third cycle on. Dehydroepiandrosterone sulfate and 17-hydroxyprogesterone significantly decreased after six cycles. The treatment did not affect glycoinsulinemic homeostasis. A trend toward an increase was seen for total cholesterol, triglycerides, and high- and low-density lipoproteins (HDL and LDL) plasma concentrations, although all parameters remained within the normal range. No modifications in total cholesterol/HDL and HDL/LDL ratios were induced by the therapy. The ethinyl estradiol/DRSP combination seems to be effective in ameliorating clinical and hormonal features of PCOS.
A Polymorphic CYP19 TTTA Repeat Influences Aromatase Activity and Estrogen Levels in Elderly Men: Effects on Bone Metabolism
Authors: Gennari Luigi , Masi Laura , Merlotti Daniela , Picariello Lucia , Falchetti Alberto , Tanini Annalisa , Mavilia Carmelo , Del Monte Francesca , Gonnelli Stefano , Lucani Barbara , Gennari Carlo , Brandi Maria Luisa
Published: June 2004

Current evidence suggests that estrogen plays a dominant role in determining bone mineral density (BMD) in men, and inactivating mutations in the aromatase CYP19 gene have been associated with low bone mass in young males. We previously reported an association between a TTTA repeat polymorphism in intron 4 of the CYP19 gene and osteoporotic risk in postmenopausal females. Here we explore the role of this polymorphism as a genetic determinant of BMD in a sample of elderly males who were recruited by direct mailing and followed longitudinally for 2 (n = 300) and 4 (n = 200) yr. Six different allelic variants, containing seven, eight, nine, 10, 11, and 12 TTTA repeats, were detected. There was a bimodal distribution of alleles, with two major peaks at seven and 11 repeats and a very low distribution of the nine-repeat allele. Men with a high-repeat genotype (>nine repeats) showed higher lumbar BMD values, lower bone turnover markers, higher estradiol levels, and a lower rate of BMD change than men with a low-repeat genotype (25), suggesting that the effect of CYP19 genotypes on bone may be masked by the increase in fat mass. Moreover, the high-repeat genotype was less represented, although not significantly, in the vertebral fracture group with respect to the nonvertebral fracture group. Functional in vitro analysis after incubation with [3H]-androstenedione showed a higher aromatase activity in fibroblasts from subjects with a high-repeat genotype than in fibroblasts from subjects with a low-repeat genotype. In conclusion, differences in estrogen levels due to polymorphism at the aromatase CYP19 gene may predispose men to increased age-related bone loss and fracture risk.
Effects of Testosterone on Mood, Aggression, and Sexual Behavior in Young Men: A Double-Blind, Placebo-Controlled, Cross-Over Study
Authors: O’Connor Daryl B. , Archer John , Wu Frederick C. W.
Published: June 2004

The prospects of wider application of testosterone (T) in novel indications such as male contraception have prompted renewed interest in the investigation of nonreproductive actions and safety of androgens. This study investigated potential changes in mood and behavior in response to elevations in circulating T concentrations produced by the new long-acting preparation, T undecanoate (TU).

Twenty-eight eugonadal men were randomized into one of two treatment groups: A1) active, receiving 1000 mg TU im followed by A2) washout, followed by A3) placebo, receiving 4 ml castor oil im; B1) placebo, 4 ml castor oil im; B2) washout followed by B3) active, receiving 1000 mg TU im. Mood, self- and partner-reported physical and verbal aggression, anger, hostility, irritability, assertiveness, self-esteem, and sexual function were assessed.

A single injection of 1000 mg TU im increased plasma T concentrations from 20.7 ± 1.5 to 37.5 ± 2.2 nmol/liter at wk 1 and 31.6 ± 1.5 nmol/liter at wk 2, and estradiol from 74.0 ± 4.9 to 120.4 ± 10.7 pmol/liter at wk 1, and 100.0 ± 6.3 pmol/liter at wk 2.

The T increment was associated with detectable but minor mood changes. Increased circulating T was associated with significant increases in anger-hostility from baseline (mean score = 7.48) to wk 2 (mean score = 10.71) accompanied by an overall reduction in fatigue-inertia (treatment = 6.21 vs. placebo = 7.84). TU treatment did not increase aggressive behavior or induce any changes in nonaggressive or sexual behavior. Changes in estradiol were not associated with any behavioral alterations.

Our results suggest that exogenous TU-induced elevation of circulating T, to the range likely to be used in hormonal male contraception, has limited psychological effects. Future research should investigate the implications of these minor mood changes.
Myocardial Blood Flow and Flow Reserve in Response to Hormone Therapy in Postmenopausal Women with Risk Factors for Coronary Disease
Authors: Duvernoy C. , Martin J. , Briesmiester K. , Bargardi A. , Muzik O. , Mosca L.
Published: June 2004

Estrogen has beneficial effects on markers of coronary heart disease (CHD) risk, but may increase overall CHD events. The effects of hormone therapy on vascular endothelial function have been mixed, and require further assessment. We studied the myocardial blood flow (MBF) response to postmenopausal combination hormone therapy (CHT) in postmenopausal women with risk factors for CHD.

We performed dynamic [13N]ammonia positron emission tomography in 15 postmenopausal women in a 7-month placebo-controlled crossover trial of continuous conjugated equine estrogen/cyclical micronized progesterone. MBF was measured at rest, after sympathetic stimulation with the cold pressor test (CPT), and after iv adenosine infusion, to determine baseline, endothelium-dependent, and maximal flows, respectively.

Response to CPT was neutral in all women at baseline (−0.51 ± 27%). Adenosine induced a marked increase in MBF (161 ± 111%). Treatment with 3 months of combined estrogen/progestin CHT did not change CPT or adenosine MBF responses. Myocardial flow reserve was unchanged as well.

In this group of postmenopausal women at higher cardiovascular risk, no association was found between CHT assignment and change in MBF. Further study is needed to clarify the effects of CHT on the endothelium of women with presumably diseased vasculature.
Testosterone Metabolic Clearance and Production Rates Determined by Stable Isotope Dilution/Tandem Mass Spectrometry in Normal Men: Influence of Ethnicity and Age
Authors: Wang Christina , Catlin Don H. , Starcevic Borislav , Leung Andrew , DiStefano Emma , Lucas Geraldine , Hull Laura , Swerdloff Ronald S.
Published: June 2004

The metabolic clearance rate (MCRT) and production rate (PRT) of testosterone (T) were measured using constant infusion of trideuterated (d3) T and quantitating serum d3T by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Serum unlabeled T (d0T) was measured by LC-MS-MS, and serum total T (d3T + d0T) was measured by RIA. Mean MCRT (measured by LC-MS-MS) in young white men (1272 ± 168 liters/d) was not significantly different from young Asian men (1070 ± 166 liters/d). Mean PRT was also not significantly different between the two ethnic groups (whites, 9.11 ± 1.11 mg/d; Asians, 7.22 ± 1.15 mg/d; P = 0.19 using d0T data). Both the mean MCRT (812 ± 64 liters/d; P < 0.01) and the PRT (3.88 ± 0.27 mg/d; P < 0.001) were significantly lower in middle-aged white men when compared with their younger counterparts. The mean MCRT and PRT calculated using serum total T or d0T data showed a diurnal variation, with levels at midday significantly higher than those measured in the evening in the young (MCRT, P < 0.01; PRT, P < 0.001) and to a lesser extent in the older men (MCRT, P < 0.05; PRT, P < 0.05 using total T and P < 0.001 using d0T data). We conclude that using LC-MS-MS to detect d3T in serum after constant infusion of stable isotope-labeled T allows the measurements of MCRT and PRT, which can be used to study androgen metabolism repeatedly after physiological or pharmacological interventions.
Diet-Induced Weight Loss Is Associated with an Improvement in β-Cell Function in Older Men
Authors: Utzschneider Kristina M. , Carr Darcy B. , Barsness Suzanne M. , Kahn Steven E. , Schwartz Robert S.
Published: June 2004

Although weight loss in older subjects has been shown to improve insulin sensitivity, it is unclear what effect this lifestyle intervention has on β-cell function. To determine whether diet-induced weight loss can improve β-cell function in older subjects, we studied 19 healthy male subjects (age, 65.4 ± 0.9 yr; body mass index, 30.9 ± 0.6 kg/m2; mean ± sem) before and after a 3-month 1200-kcal/d diet. The insulin sensitivity index (SI) was quantified using Bergman’s minimal model. The acute insulin response to glucose (AIRg) and the maximal glucose-potentiated insulin response (AIRmax) were determined and then adjusted for SI (SI × AIRg and SI × AIRmax), thus providing measures of β-cell function. Subjects demonstrated significant weight loss (95.6 ± 2.4 to 86.1 ± 2.5 kg; P < 0.001). Both fasting plasma glucose [97.3 ± 1.6 to 95.1 ± 1.3 mg/dl (5.4 ± 0.09 to 5.3 ± 0.07 mm); P = 0.05] and insulin [18.5 ± 1.3 to 12.2 ± 1.0 μU/ml (110.9 ± 7.7 to 73.5 ± 5.9 pm); P < 0.001] levels decreased. With weight loss, SI increased [1.59 ± 0.24 to 2.49 ± 0.32 × 10−4 min−1/(μU/ml) (2.65 ± 0.4 to 4.15 ± 0.5 × 10−5 min−1/pm); P < 0.001], whereas both AIRg [63.4 ± 13.4 to 51.0 ± 10.7 μU/ml (380 ± 80 to 306 ± 64 pm); P < 0.05] and AIRmax [314 ± 31.4 to 259.9 ± 33.4 μU/ml (1886 ± 188 to 1560 ± 200 pm); P < 0.05] decreased. Overall β-cell function improved (SI × AIRg, 9.63 ± 2.28 to 12.78 ± 2.58 × 10−3 min−1, P < 0.05; and SI × AIRmax, 51.01 ± 9.2 to 72.69 ± 13.4 × 10−3 min−1, P < 0.05). Thus, the weight loss-associated improvements in both insulin sensitivity and β-cell function may explain the beneficial effects of a lifestyle intervention on delaying the development of diabetes in older subjects.
Recombinant Human Chorionic Gonadotropin But Not Dihydrotestosterone Alone Stimulates Osteoblastic Collagen Synthesis in Older Men with Partial Age-Related Androgen Deficiency
Authors: Meier Christian , Liu Peter Y. , Ly Lam P. , de Winter-Modzelewski James , Jimenez Mark , Handelsman David J. , Seibel Markus J.
Published: June 2004

Several randomized trials of androgen supplementation in older men have been undertaken. However, the relative contributions of testosterone (T) and estrogens on bone metabolism in aging men are controversial. Within the setting of two double-blind, placebo-controlled studies, we evaluated the effect of dihydrotestosterone (DHT) and recombinant human chorionic gonadotropin (rhCG) on bone turnover in healthy, community-dwelling older men with partial androgen deficiency (total T ≤ 15 nmol/liter). In the first study, 35 men (age 68.3 ± 6.8 yr; baseline T, 13.9 ± 3.3 nmol/liter) were randomized to receive either daily transdermal DHT (n = 17) or placebo for 3 months. In the second study, 40 men (age 67.4 ± 5.4 yr; baseline T, 11.4 ± 2.2 nmol/liter) were randomized to receive either rhCG sc (n = 20), two injections weekly, or placebo for 3 months. The following parameters were measured before, monthly during, and 1 month after treatment: serum T, estradiol (E2), and LH; markers of bone formation, serum amino-terminal propeptide of type I procollagen (S-PINP) and osteocalcin; markers of bone resorption, serum carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline. Compared with placebo, treatment with DHT significantly increased serum DHT and suppressed LH and T levels, whereas E2 concentrations and markers of bone turnover did not change. In contrast, rhCG therapy significantly increased both T and E2, with the increases in E2 being supraphysiological. At the same time, rhCG significantly increased S-PINP concentrations with peak levels after 1 month (Δ40%; P = 0.02 compared with placebo). In contrast, serum osteocalcin and carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline levels did not change. The change in S-PINP levels correlated with the change in E2 levels (r = 0.59; P = 0.02) but not with a change in T.

We conclude that in older men with partial age-related androgen deficiency, rhCG treatment stimulates osteoblastic collagen formation proportionally to increased E2 concentrations but does not alter markers of mature osteoblastic function or bone resorption. In contrast, treatment with a pure, nonaromatizable androgen (DHT) has no effect on bone turnover despite a 20-fold increase in serum levels. Bone resorption was not accelerated during unchanged (DHT) or increased (rhCG) E2 levels, suggesting that minimal E2 levels are needed to maintain stable resorption, although direct androgen receptor-mediated effects cannot be excluded. If androgen supplementation is required for aging men, aromatizable androgens with sufficient endogenous estrogenic activity may have the most beneficial effects on bone.
Pharmacological Treatment of Insulin Resistance at Two Different Stages in the Evolution of Type 2 Diabetes: Impact on Glucose Tolerance and β-Cell Function
Authors: Xiang Anny H. , Peters Ruth K. , Kjos Siri L. , Goico Jose , Ochoa Cesar , Marroquin Aura , Tan Sylvia , Hodis Howard N. , Azen Stanley P. , Buchanan Thomas A.
Published: June 2004

The purpose of this study was to compare the impact of treating insulin resistance with a thiazolidinedione drug before vs. at the onset of diabetes on glucose levels and β-cell function.

Nondiabetic Hispanic women of Mexican or Central American descent with prior gestational diabetes mellitus (GDM) were randomized to troglitazone (early intervention), 400 mg/d, or placebo (later intervention). Women who developed diabetes were placed on open-label troglitazone. Glucose tolerance, insulin resistance, and β-cell function were measured at randomization, at the diagnosis of diabetes, and 8 months post trial to determine the long-term impact of the two treatment strategies on glucose levels and β-cell function.

During a mean follow-up of 4.3 yr between baseline and posttrial tests, glucose tolerance (oral glucose tolerance test glucose area, P = 0.04) and insulin resistance (MINMOD SI, P = 0.02) worsened more in women randomized to late intervention (n = 69) than to early intervention (n = 57). Insulin secretion (acute insulin response in the iv glucose tolerance test, P = 0.09) and β-cell compensation for insulin resistance (disposition index, P = 0.07) also tended to worsen more in the late intervention group. Among women in the late intervention group who developed diabetes, oral glucose tolerance test glucose area (P = 0.0001) and β-cell function (P ≤ 0.04) deteriorated significantly during development of diabetes on placebo and then did not change significantly (P > 0.50) during treatment with troglitazone and posttreatment washout.

In high-risk Hispanic women, amelioration of insulin resistance can stabilize glycemia at the time diabetes develops. These findings highlight the role of insulin resistance in the genesis of progressive β-cell dysfunction during the evolution of type 2 diabetes.
Changes in Muscle Myostatin Expression in Obese Subjects after Weight Loss
Authors: Milan G. , Dalla Nora E. , Pilon C. , Pagano C. , Granzotto M. , Manco M. , Mingrone G. , Vettor R.
Published: June 2004

Myostatin is a member of transforming growth factor-β superfamily that plays an important inhibitory role during muscle development; in fact mutations of myostatin gene result in a hypermuscular phenotype. Moreover myostatin-deficient mice have a significant reduction in fat depots and a depression of adipogenesis. Little is known about myostatin function in muscle growth regulation in humans and in particular during caloric restriction. In the present work we quantified by real-time RT-PCR myostatin expression in muscle biopsies of a group of morbidly obese patients before and after weight loss obtained by biliopancreatic diversion (BPD). The patients reduced body weight by 38.9%, mostly due to fat-mass loss, showing also a significant reduction in the 24-hour EE as assessed by the respiratory chamber. Myostatin mRNA levels result clearly decreased after weight loss, suggesting a role in counteracting the progressive decline of muscle mass after BPD. Myostatin may provide therefore another mechanistic explanation for the control of energy partitioning between protein and fat, working against muscle wasting. Our data suggest that myostatin might represent an important regulator of skeletal muscle size also in conditions of food restriction in obese subjects.
Detection of BRAF Mutation on Fine Needle Aspiration Biopsy Specimens: A New Diagnostic Tool for Papillary Thyroid Cancer
Authors: Xing Mingzhao , Tufano Ralph P. , Tufaro Anthony P. , Basaria Shehzad , Ewertz Marge , Rosenbaum Eli , Byrne Patrick J. , Wang James , Sidransky David , Ladenson Paul W.
Published: June 2004

Numerous biomolecular markers have been studied to improve the accuracy of fine needle aspiration biopsy (FNAB) in the diagnostic and prognostic evaluation of thyroid tumors, but none of them has yet become clinically useful. The recently discovered BRAF mutation, which occurs specifically in papillary thyroid cancers (PTC) with a high prevalence and is associated with poor clinicopathological outcomes, has the potential to be a useful diagnostic and prognostic marker for PTC. In the present study, we investigated whether detection of BRAF mutation on FNAB specimens was technically possible and could be used as an adjunct diagnostic tool with routine FNAB. Evaluation of a new colorimetric mutation detection method demonstrated 100% sensitivity and 100% specificity in comparison with conventional DNA sequencing as the “gold standard” in a large pool of DNA samples from various primary thyroid tumor specimens and cell lines. We found this novel technique even more sensitive in detecting BRAF mutation on FNAB specimens than conventional sequencing. In a series of 48 patients undergoing thyroidectomy, mostly for thyroid cancer or for suspicion of cancer, we performed preoperative FNAB and, using the colorimetric mutation detection method, identified BRAF mutation on the cytological specimens. Prospective analysis showed that 50% of the nodules that proved to be PTC on surgical histopathology were correctly diagnosed by BRAF mutation analysis on FNAB specimens; there were no false positive findings. Thus, we have demonstrated the usefulness of BRAF mutation detection on FNAB specimens that can help diagnose and identify those PTC patients who may need more aggressive surgical treatment and vigilant clinical monitoring.
Serum Inhibin B and Follicle-Stimulating Hormone Levels as Tools in the Evaluation of Infertile Men: Significance of Adequate Reference Values from Proven Fertile Men
Authors: Andersson Anna-Maria , Petersen Jørgen H. , Jørgensen Niels , Jensen Tina K. , Skakkebæk Niels E.
Published: June 2004

Inhibin B and FSH levels in 289 idiopathic infertile men were compared with reference materials consisting of 303 proven fertile men (reference group 1) and 307 healthy men from the general population with unknown fertility status (reference group 2). The diagnostic power of these two serum markers of spermatogenesis was evaluated by the use of receiver operating characteristic plot analysis, and an example of how both markers can be used simultaneously in a bivariate reference chart is presented.

Inhibin B levels were significantly lower and FSH levels were significantly higher in the infertile men, compared with either reference group, but with significant overlap, especially with reference group 2. Nevertheless, approximately 50% of the infertile men had an inhibin B or FSH, respectively, below the 2.5 percentile or above the 97.5 percentile of reference group 1, whereas only approximately 25% of the infertile men had an inhibin B or FSH, respectively, below the 2.5 percentile or above the 97.5 percentile of reference group 2. Fourteen and 11% of reference group 2 had an inhibin B or FSH, respectively, below the 2.5 percentile or above the 97.5 percentile of reference group 1, suggesting that a significant number of individuals from the general population with unknown fertility but otherwise healthy may actually be subfertile.

In conclusion, 1) proven fertile men constitute the most appropriate reference group in the evaluation of the FSH-inhibin B axis; the sensitivity of these markers to identify infertility increased by approximately 20% when fertile men rather than men from the general population were used as control group; 2) FSH alone had a slightly higher positive predictive value than inhibin B alone, but the positive predictive value were highest when both markers of spermatogenesis were used in an inhibin B/FSH ratio; and 3) a bivariate reference chart is a valuable objective tool in the simultaneous evaluation of FSH and inhibin B as two interrelated markers.