bluuebunny/crossref_metadata_2025_split huggingface dataset:
GnRHa flare and IVF pregnancy rates
Authors: Confino E. , Zhang X. , Kazer R.R. 
Published: November 2003

AbstractObjectives: GnRH agonist administered early in the menstrual cycle (flare) causes an endogenous discharge of FSH and LH. Flare has been used in conjunction with gonadotropin ovarian stimulation for IVF ‘poor responders’. There is an ongoing controversy regarding whether flare protocols improve pregnancy rates in ‘poor responders’. The current study was designed to compare a GnRHa flare protocol with long suppression GnRHa IVF in ‘poor responders’. Methods: Seventy‐three newly diagnosed poor responders who failed long GnRHa suppression IVF attempts were compared retrospectively with 128 age‐matched IVF patients previously known poor ovarian responders treated with a long GnRHa suppression protocol. ‘Poor responders’ consisted of patients with peak E2 less than 1000 pg/ml and/or less than five mature follicles with diameter >15 mm on the day of hCG administration. Student's t‐test was used to analyze the data and the chi‐squared test was used to compare fertilization and pregnancy rates. Results: The flare protocol produced higher peak E2 levels (1647±747 vs. 720±258 mIU/ml, P<0.05) and a larger number of mature follicles (5.8±2.2 vs. 4.0±1.0 P<0.05) in the study vs. the control group. A 30% pregnancy rate was achieved during this second IVF attempt using GnRHa flare protocol in the study group vs. 37 in the control group (P>0.05, NS). Conclusions: A comparison between the flare protocol group and the age‐matched control group of poor ovarian responders subject to down regulation protocol, revealed higher peak E2 levels and more mature follicles, respectively. However, both groups yielded comparable pregnancy rates. The use of high dose gonadotropin treatment in our study groups seems to be the only explanation for their subsequent successful outcome. We concluded that GnRH agonist flare protocol does not result in better IVF outcome compared with long GnRH agonist suppression protocol in IVF poor responders.
Clinical trials update from the European Society of Cardiology: CHARM, BASEL, EUROPA and ESTEEM
Authors: Coletta Alison P. , Cleland John G.F. , Freemantle Nick , Loh Huan , Memon Anwar , Clark Andrew L. 
Published: November 2003

AbstractThis article contains a series of reports on recent research developments in the field of heart failure. Reports of key presentations made at the European Society of Cardiology meeting, held in Vienna, Austria, between 30 August and 3 September 2003 are reported. In the CHARM study, candesartan reduced cardiovascular deaths and hospital admissions for heart failure, both in patients who were already taking an ACE‐inhibitor and in those who were ACE intolerant. However, results in patients with preserved left ventricular function were less conclusive. The BASEL study supports the use of B‐type natriuretic peptide testing to confirm the diagnosis of heart failure in patients presenting with acute dyspnoea. In EUROPA, the largest ever study of secondary prevention of coronary artery disease, long‐term treatment with perindopril reduced the incidence of cardiovascular death, myocardial infarction (MI) and cardiac arrest. The ESTEEM study showed that the oral thrombin inhibitor ximelagatran plus aspirin was more effective than aspirin alone in the prophylaxis of major cardiovascular events following MI.
Efficacy and safety of oral candesartan cilexetil in patients with congestive heart failure
Authors: Matsumori Akira ,   on behalf of the assessment of response to candesartan in heart failure in Japan (ARCH‐J) study investigators
Published: November 2003

AbstractBackground:Candesartan cilexetil is a new angiotensin II receptor blocker with a high affinity for the angiotensin II‐subtype 1 receptor.Aims:This 6‐month study examined the safety and efficacy of candesartan cilexetil, 8 mg once daily, to prevent the progression of congestive heart failure (CHF).Methods:This randomised, double‐blind, placebo‐controlled study enrolled 305 patients with CHF who were not receiving ACE inhibitor therapy. The composite primary efficacy endpoint was progression of CHF or addition or dose escalation of CHF medications. The secondary endpoints were incidence of cardiovascular events and changes in left ventricular function.Results:The study was prematurely terminated after the second interim safety analysis. The incidence of confirmed progression of CHF was significantly lower in the candesartan group (7.4%) than in the placebo group (22.2%), with a risk reduction of 66.7% and a risk difference of −14.8% (95% CI: −22.8 to −6.8%, P<0.001). Cardiovascular events were also significantly lower during treatment with candesartan than with placebo (10.8% vs. 22.9%) with a risk reduction of 52.8% and a risk difference of −12.1% (95% CI: −20.6 to −3.6%, P<0.01). The actively treated group had a significant improvement in hemodynamics. Candesartan cilexetil was well tolerated.Conclusion:Candesartan cilexetil, 8 mg/day, significantly reduced the progression of CHF when compared with placebo.
Mutations in the low‐density‐lipoprotein receptor gene in German patients with familial hypercholesterolaemia
Authors: Weiss N. , Binder G. , Keller C. 
Published: November 2003

AbstractFamilial hypercholesterolaemia (FH) is an autosomal dominant disorder of lipid metabolism characterized by elevated low‐density lipoproteins (LDL), the formation of tendon and skin xanthomata and the development of premature coronary atherosclerosis. It is caused by a defect in the receptor‐mediated hepatic uptake of LDL due to mutations in the LDL receptor. In 25 FH families with a total of 160 members and in two individuals without available relatives, all of German origin, we identified LDL receptor mutations by a multiplex‐PCR‐based single‐strand conformation polymorphism method followed by direct sequencing. Of the 24 mutations found, 15 are missense mutations, 2 are nonsense mutations, 4 are small deletions or insertions leading to frameshifts, 2 are an in‐frame insertion and deletion, respectively, and one is a splice site mutation. Propositi carrying mutations that are known to completely abolish receptor function (nonsense and frameshift mutations, missense mutation V480M) had significantly higher untreated total and LDL‐cholesterol levels compared to those patients carrying missense and in‐frame insertion mutations of unknown functional consequence, which may lead to either reduced or completely abolished receptor function (11.30±1.64 vs 9.76±1.50 mmol/L, and 9.39±1.23 vs 7.99±1.45 mmol/L, respectively). These results confirm the clinical and molecular heterogeneity of FH and the influence of different functional classes of mutations on lipid values.
Trifunctional protein deficiency: Three families with significant maternal hepatic dysfunction in pregnancy not associated with E474Q mutation
Authors: Chakrapani A. , Olpin S. , Cleary M. , Walter J. H. , Wraith J. E. , Besley G. T. N. 
Published: November 2003

AbstractWe report five families with trifunctional protein deficiency in which, during pregnancy, three mothers experienced significant hepatic disease when carrying an affected fetus. Diagnoses were based on increased levels of long‐chain hydroxyacylcarnitines and deficiencies of 3‐hydroxyacyl‐CoA dehydrogenase (LCHAD) and 3‐ketoacyl‐CoA thiolase activity in fibroblasts. All affected infants lacked the common E474Q mutation associated with isolated LCHAD deficiency. This mutation is thought to be a predisposing factor for maternal hepatic disease in pregnancy. Our findings suggest that other defects in this enzyme complex might be responsible for maternal hepatic complications in pregnancy.
Hepatocellular carcinoma despite long‐term survival in chronic tyrosinaemia I
Authors: Kim S. Z. , Kupke K. G. , Ierardi‐Curto L. , Holme E. , Greter J. , Tanguay R. M. , Poudrier J. , D'Astous M. , Lettre F. , Hahn S. H. , Levy H. L. 
Published: November 2003

AbstractTyrosinaemia I (fumarylacetoacetate hydrolase deficiency) is an autosomal recessive inborn error of tyrosine metabolism that produces liver failure in infancy or a more chronic course of liver disease with cirrhosis, often complicated by hepatocellular carcinoma, in childhood or early adolescence. We studied a 37‐year‐old woman with tyrosinaemia I whose severe liver disease in infancy and rickets during childhood resolved with dietary therapy. From 14 years of age she resumed an unrestricted diet with the continued presence of the biochemical features of tyrosinaemia, yet maintained normal liver function. In adult years she accumulated only small amounts of succinylacetone. Despite this evolution to a mild biochemical and clinical phenotype, she eventually developed hepatocellular carcinoma. Her fumarylacetoacetate hydrolase genotype consists of a splice mutation, IVS6−1g>t, and a novel missense mutation, Q279R. Studies of resected liver demonstrated the absence of hydrolytic activity and of immunological expression of fumarylacetoacetate hydrolase in liver tumour. In nontumoral areas, however, 53% of normal hydrolytic activity and immunologically present fumarylacetoacetate hydrolase was found. This case demonstrates the high risk of liver cancer in tyrosinaemia I even in a seemingly favourable biological environment.
Plasma creatinine assessment in creatine deficiency: A diagnostic pitfall
Authors: Verhoeven N. M. , Guérand W. S. , Struys E. A. , Bouman A. A. , van der Knaap M. S. , Jakobs C. 
Published: November 2003

AbstractGuanidinoacetate methyltransferase (GAMT) deficiency (creatine deficiency syndrome) is a recently discovered inborn error of creatine biosynthesis. Affected patients have elevated concentrations of guanidinoacetate, the metabolic precursor of creatine, in urine, plasma and cerebrospinal fluid. In addition, urinary creatinine excretion and plasma creatinine concentration are decreased. For biochemical evaluation of patients suspected to suffer from GAMT deficiency, correct quantification of creatinine in plasma is important. Here we report our experience with different quantification techniques. We found that creatinine in plasma from two GAMT‐deficient patients appeared normal when measured by the Jaffé method but was decreased when measured enzymatically or by HPLC. The apparently normal levels of creatinine as measured by the Jaffé method were not caused by guanidinoacetate. In urine, the Jaffé method and the enzymatic method gave similar results, indicating that in urine no false elevations of creatinine can be expected. As the Jaffé method is still widely used for routine plasma creatinine measurements, it is important to realize it cannot be used to exclude GAMT deficiency.
Treating glucosphingolipid disorders by chemotherapy: Use of approved drugs and over‐the‐counter remedies
Authors: Radin N. S. 
Published: November 2003

AbstractThe accumulation of a glucosphingolipid (GSL) in individuals lacking an adequate level of hydrolase activity could be minimized by chemotherapeutic measures that slow the formation of the GSL and stimulate the defective hydrolase. By achieving a balance in the rates of formation and breakdown, one should be able to alleviate the symptoms of excess storage and achieve a satisfactory accommodation. While several drugs seem to be specifically suitable for this purpose, only one of these has been approved for human use. However, less effective drugs and over‐the‐counter substances are available for human use and may prove satisfactory for a few years until better ones are made available. The proposed materials and the evidence behind the recommendations are presented in this paper.
Axial–transverse fluvial interactions in half‐graben: Plio‐Pleistocene Palomas Basin, southern Rio Grande Rift, New Mexico, USA
Authors: Leeder M. R. , Mack G. H. , Salyards S. L. 
Published: November 2003

Accurate magnetostratigraphic dating of Plio‐Pleistocene alluvium in the Palomas half‐graben permits correlation of transverse and axial deposits, thus enabling analysis of the movement of alluvial facies belts in time and space for the first time. Northern areas show evidence for basinward progradation of footwall‐sourced Matuyama‐age alluvial fan deposits over axial channel belt deposits of the ancestral Rio Grande, despite both deposits having similar deposition rates. This gradual ‘forced’ westward migration of the axial belt was in opposition to ongoing eastward growth of hangingwall‐sourced fans and tectonic tilt imposed by the bounding Caballo normal fault. Fan growth was coincident with a recently proposed gradual climatic shift that may have increased sediment flux out of transverse catchments. It is also possible that continuing tectonic footwall uplift and divided retreat caused catchment areas to increase, contributing to these trends.Southern areas of the Palomas half‐graben feature late Gilbert/early Gauss deposits indicative of rapid westwards progradation of large low‐gradient, footwall‐sourced fans over axial deposits. This ‘forced’ migration of the ancestral Rio Grande may have occurred due to footwall catchment and fan growth consequent upon initiation and growth of the Red Hills Fault. Subsequent eastward movement of the axial channel belt in late Gauss and Matuyama times overwhelmed these large fans. We attribute this to continued tilting on the Red Hills Fault and to development of the Jornada Fault to the south‐east, the axial river belt avulsing north and eastwards through a developing Red Hills/Jornada crossover transfer zone.We conclude generally that facies architecture of axial and transverse elements in half‐graben must reflect both climatic influences and the effects of fault development. Careful field mapping, accurate dating and palaeoclimatic studies are all necessary to determine the relative importance of these controls. Although adequate as broad guides, previous purely ‘fixist’ tectonosedimentary models allow for no fault growth, decay or climatic modulation of facies trends and are thus generally inadequate to explain important aspects rift basin stratigraphy.
Plan‐view curvature of foreland basins and its implications for the palaeostrength of the lithosphere underlying the western Alps
Authors: Sinclair H. D. 
Published: November 2003

In zones of continental collision, three methods can be used to calculate the strength of the underthrust lithosphere: (1) a forward model approach to the Bouguer gravity field, (2) an inverse model of the gravity and topography using admittance techniques, or (3) a forward model of the stratigraphic infill of the foreland basin to estimate the cross‐sectional profile of the downflexed plate. The use of reconstructed stratigraphy has the potential to yield values for the equivalent elastic thickness (Te) of the cratonic lithosphere at varying slices in geological time, and hence enable an insight into the longer term (10–50 Myr) mechanical behaviour of the continental lithosphere.Calculations of Te based on isopachs of foreland basin stratigraphy use sea level as a reference line to estimate the basement deflection, and therefore are limited to using stratigraphy which records shallow marine or coastal sedimentation. A new empirical approach is applied to evaluating ancient Te values using the reconstructed palaeocurvature of the basin in plan view. The radius of curvature of 12 curvilinear foreland basins is plotted against their documented Te values and shows a linear relationship. The maximum Te value for a given radius of curvature can also be plotted as a straight line. The palaeocurvature of reconstructed basins can then be compared with the plots, and estimates of likely maximum Te values may be obtained.During Eocene times, the underfilled foreland basin of the Alps was characterized on its cratonic edge by the deposition of Nummulite‐rich limestones. Palaeogeographical reconstructions of the Nummulitic Limestones enable estimates of the palaeocurvature of the cratonic margin of the Alpine foreland basin during the Eocene. By comparing this value with the curvature of documented basins, it is possible to suggest that the European lithosphere underlying the western Alps had an effective elastic thickness of no greater than 17 km during the Eocene. It has been suggested that the transition in the depositional state of the Alpine foreland basin from an underfilled to a filled state during middle Oligocene times was linked to a thickening of the continental lithosphere associated with the effective ramp of the Tethyan passive margin. The Te value of less than 17 km during the underfilled stage combined with a value of 10±5 km for the later filled stage at 17 Ma does not lend support to this hypothesis.
Tectonic geomorphology of the Ash Hill fault, Panamint Valley, California
Authors: Densmore Alexander L. , Anderson Robert S. 
Published: November 2003

ABSTRACTPanamint Valley, in eastern California, is an extensional basin currently bounded by active, dextral‐normal oblique‐slip faults. There is considerable debate over the tectonic and topographic evolution of the valley. The least‐studied structure, the Ash Hill fault, runs for some 50 km along the valley’s western edge, and active strands of the fault continue south into the neighbouring Slate Range. Vertical displacement on the fault is valley‐side up, creating topography that conflicts with the gross morphology of the valley itself. We use this topography, along with kinematic and geological markers, to constrain the Quaternary slip rate and orientation of the Ash Hill fault. The fault offsets all but the active channel deposits in the valley, and slickenlines indicate a strike‐slip to dip‐slip ratio of 3.5:1. An offset volcanic unit dated at 4 Ma provides a minimum slip rate of 0.3±0.1 mm yr−1, and a long‐term strike‐slip to dip‐slip ratio of 5.2:1. Slip on the fault has warped a palaeolake shoreline within the valley. Simple elastic dislocation modelling of the vertical deformation of the shoreline suggests total fault slip of ≈60 m, valley‐side up. The shoreline probably dates to 120–150 ka, implying a late Quaternary slip rate of 0.4–0.5 mm yr−1. We suggest two possible mechanisms for the apparently anomalous slip behaviour of the Ash Hill fault. The fault may be a listric structure related to the proposed low‐angle fault underlying Panamint Valley. Alternatively, the Ash Hill fault is a high‐angle fault, implying that the valley is currently bounded by high‐angle dextral‐slip faults. Lack of detailed subsurface information precludes any knowledge of the true relationships between the presently active faults.
The Rioja Trough (N Spain): tectosedimentary evolution of a symmetric foreland basin
Authors: Muñoz‐Jiménez A. , Casas‐Sainz A. M. 
Published: November 2003

ABSTRACTThe Rioja Trough is the foreland basin of the western Pyrenees (to the north) and the Cameros‐Demanda Massif (to the south). This E–W elongated trough is about 120×35 km. It was filled with Tertiary continental deposits (upper Eocene to upper Miocene), reaching thicknesses between 2500 and 5000 m. Both margins of the Rioja Trough are large thrusts with horizontal displacements of more than 20 km basinward. Rocks that fill the basin originated in alluvial fan and playa‐lake environments, with conglomerates in the proximal sectors grading into sandstones, mudstones, lacustrine limestones and evaporites in distal sectors. The Tertiary series are horizontal in the central parts of the basin, with several E–W monoclines caused by north‐verging thrusts in the basement of the basin. Near the basin margins, the Tertiary units are folded and thrusted, with several syntectonic unconformities. Calculated velocities for the Cameros‐Demanda thrust range from 0.02 to1.1 mm yr−1 (average 0.7 mm yr−1). The sedimentation rate near the southern basin margin varies between 2 and 20 cm 1000 yr−1 (average 10 cm 1000 yr−1). Deposition in the Rioja Trough was strongly controlled by tectonic activity throughout the Tertiary. Eight tectosedimentary units (R1 to R8) have been characterized. These are bounded by angular unconformities at the margins and breaks in the vertical trend of the sedimentary record toward the basin centre. Every tectosedimentary unit (except R6 and R8) shows a fining‐upward/coarsening‐upward trend, corresponding to tectonic retrogradations and progradations, respectively. The main source area during the Palaeogene was the Cameros‐Demanda Massif, whose unroofing sequence was strongly dependent on tectonic activity. During the Neogene a longitudinal WNW–ESE drainage system, with short alluvial fans in the northern and southern margins, developed. The final shape and the evolution of the Rioja Trough are the result of crustal flexure in the northern border of the Iberian plate, linked to the emplacement of the southern Pyrenean thrust system, and intraplate thrusting with basement uplift at its southern margin.
Tectonic modelling of the Middle Jurassic synrift stratigraphy in the Oseberg–Brage area, northern Viking Graben
Authors: Ter Voorde M. , Ravnås R. , Færseth R. , Cloetingh S. 
Published: November 2003

A finite difference model, allowing for episodic movements along different faults, is used to examine the effect of tectonics on the stratigraphic signature in the Oseberg–Brage area in the northern Viking Graben. Constraints are provided by local exploration and production well data and 3‐D seismic coverage, and a regional depth‐converted seismic line.In the modelling, we focus on the influence of varying rates of fault movement on stratigraphic signatures such as upflank unconformities and changes in layer thickness. We couple the basinwide features of the northern Viking Graben with the fault‐block‐scale features of the Oseberg–Brage area by using parameter constraints derived by large‐scale modelling as input for the local‐scale model. In addition, subsidence patterns resulting from the basinwide model were used as background subsidence for the fault block model of the Oseberg–Brage area.The model results indicate that the alternating activation of different faults with varying extension rates can cause stratigraphic features such as unconformities, condensation and onlap/offlap patterns. Onlap occurs during periods of low extension rates. An increase in extension rate along a fault causes footwall uplift, resulting in condensation or upflank erosion yielding unconformities. This influence can also affect sub‐basins further away from the fault. Downdip layer thickening reflects the local tilting of fault blocks.The coupling of the local and regional scales turns out to be essential in explaining the stratigraphy of the Oseberg–Brage area: basinward and, notably, updip layer thickening as observed on some of the fault blocks can only be explained by activity of the boundary fault on the opposing, western margin of the northern Viking Graben.