bluuebunny/crossref_metadata_2025 huggingface dataset:
Biochemical characterization of muscle tissue of limb girdle muscular dystrophy: An 1H and 13C NMR study
Authors: Sharma Uma , Atri Surinder , Sharma M. C. , Sarkar Chitra , Jagannathan N. R.
Published: October 2003

The metabolic differences between the muscle biopsies of patients with limb girdle muscular dystrophy (LGMD) and normal controls were characterized using high‐resolution 1H and 13C NMR spectroscopy. In all, 44 metabolites were unambiguously assigned in the perchloric acid extracts of skeletal muscle tissue, using 2D double quantum filtered (DQF COSY), total correlation (TOCSY), and 1H/13C heteronuclear multiple quantum coherence (HMQC) spectroscopy. The concentrations of glycolytic substrate, glucose (p = 0.03), gluconeogenic amino acids, glutamine (p = 0.02) and alanine (p = 0.009) together with glycolytic product, lactate (p = 0.04), were found to be significantly lowered in LGMD patients as compared with controls. The reduction in the concentration of glucose may be attributed to the decrease in the concentration of gluconeogenic amino acids in the degenerated muscle. Reduction in the rate of anaerobic glycolysis and lowered substrate concentration appear to be the possible reasons for the decrease in the concentration of lactate. A significant reduction in the concentration of choline in LGMD patients was also observed compared with controls. Lower concentration of choline may be the result of decreased rate of membrane turnover in LGMD patients. The data presented here provide an insight into the potentials of in‐vitro NMR spectroscopy in the study of muscle metabolism. Copyright © 2003 John Wiley & Sons, Ltd.
Two‐dimensional NMR spectroscopy of urinary glycosaminoglycans from patients with different mucopolysaccharidoses
Authors: Hochuli Michel , Wüthrich Kurt , Steinmann Beat
Published: October 2003

Patients with different types of mucopolysaccharidoses (MPS) lack specific lysosomal enzymes, which leads to tissue accumulation and urinary excretion of glycosaminoglycans (GAGs). Since little is known about the molecular composition of the excreted GAG fragments, we used two‐dimensional [1H,13C]‐correlation nuclear magnetic resonance (NMR) spectroscopy for a detailed analysis of the urinary GAGs of patients with MPS types I, II, IIIA, IVA and VI. The method revealed that the molecular structures of the excreted GAGs, i.e. heparan sulfate (HS), dermatan sulfate (DS), chondroitin sulfate (CS), and keratan sulfate (KS) are clearly distinct for the different MPS types. The chain terminal residues that are the normal substrates for the defective enzymes constitute characteristic sets of signals for each MPS type. The GAG chains show variations in carbohydrate composition and sulfation patterns that can be related to the different MPS types and clinical features. For example, two patients with MPS IIIA (M. Sanfilippo) with signs of CNS degeneration but only mild somatic features excrete a highly sulfated variant of HS, resembling HS in porcine brain, whereas a patient with MPS I (M. Scheie) and two patients with MPS II (M. Hunter), who present primarily with coarse facial features, joint contractures and skeletal deformities excrete a different type of HS with lower sulfation. In another case study, a patient with MPS IVA (M. Morquio), who presented mainly with skeletal dysplasia, excreted not only excessive amounts of KS but also a highly sulfated CS variant, resembling CS in articular cartilage. The high‐resolution NMR analysis of urinary GAGs presented here for the first time provides a solid basis for future studies with a larger number of patients to further explore pathogenesis and course of the MPS diseases. Copyright © 2003 John Wiley & Sons, Ltd.
Limits on volume changes in the mushroom bodies of the honey bee brain
Authors: Fahrbach Susan E. , Farris Sarah M. , Sullivan Joseph P. , Robinson G.E.
Published: October 2003

The behavioral maturation of adult worker honey bees is influenced by a rising titer of juvenile hormone (JH), and is temporally correlated with an increase in the volume of the neuropil of the mushroom bodies, a brain region involved in learning and memory. We explored the stability of this neuropil expansion and its possible dependence on JH. We studied the volume of the mushroom bodies in adult bees deprived of JH by surgical removal of the source glands, the corpora allata. We also asked if the neuropil expansion detected in foragers persists when bees no longer engage in foraging, either because of the onset of winter or because colony social structure was experimentally manipulated to cause some bees to revert from foraging to tending brood (nursing). Results show that adult exposure to JH is not necessary for growth of the mushroom body neuropil, and that the volume of the mushroom body neuropil in adult bees is not reduced if foraging stops. These results are interpreted in the context of a qualitative model that posits that mushroom body neuropil volume enlargement in the honey bee has both experience‐independent and experience‐dependent components. © 2003 Wiley Periodicals, Inc. J Neurobiol 57:141–151, 2003
Dehydroepiandrosterone upregulates neural androgen receptor level and transcriptional activity
Authors: Lu Shi‐Fang , Mo Qianxing , Hu Shan , Garippa Carrie , Simon Neal G.
Published: October 2003

The mechanism of action of dehydroepiandrosterone (DHEA), a neuroactive neurosteroid synthesized in the brains of humans and other mammals, has not been fully characterized in the adult brain. Although well known for modulatory effects on GABAA, NMDA, and σ1 receptors, studies in both CNS and peripheral target cells suggest that DHEA also may exert genomic effects via the androgen receptor (AR). The current study tested the hypothesis that DHEA was capable of producing androgenic effects in the CNS by assaying its ability to induce three characteristic effects of an androgenic compound. These included the ability to upregulate neural AR protein level in mouse brain and immortalized GT1–7 hypothalamic cells, the capacity to induce transcriptional activity through AR in CV‐1 cells transfected with an MMTV‐ARE‐CAT reporter, and competition for recombinant AR binding in a radioligand binding assay. The results showed that DHEA treatment significantly augmented AR both in vivo and in vitro, and that this effect was not blocked by trilostane (TRIL), a known 3β‐hydroxysteroid dehydrogenase (3β‐HSD) inhibitor. DHEA also promoted AR‐mediated CAT reporter expression and competed with dihydrotestosterone (DHT) for binding to recombinant AR in a cell‐free system. These data indicate that DHEA possesses intrinsic androgenic activity that is potentially independent of metabolic conversion to other androgens, and that it can affect gene function through the AR. In combination with its modulation of neurotransmitter receptors at the cell membrane level, the findings suggest that the mechanism of action of DHEA in the brain can involve a “crosstalk” cellular signaling system that involves both nongenomic and genomic components. © 2003 Wiley Periodicals, Inc. J Neurobiol 57: 163–171, 2003
Neural correlates to flight‐related density‐dependent phase characteristics in locusts
Authors: Fuchs E. , Kutsch W. , Ayali A.
Published: October 2003

Locust phase polymorphism is an extreme example of behavioral plasticity; in response to changes in population density, locusts dramatically alter their behavior. These changes in behavior facilitate the appearance of various morphological and physiological phase characteristics. One of the principal behavioral changes is the more intense flight behavior and improved flight performance of gregarious locusts compared to solitary ones. Surprisingly, the neurophysiological basis of the behavioral phase characteristics has received little attention. Here we present density‐dependent differences in flight‐related sensory and central neural elements in the desert locust. Using techniques already established for gregarious locusts, we compared the response of locusts of both phases to controlled wind stimuli. Gregarious locusts demonstrated a lower threshold for wind‐induced flight initiation. Wind‐induced spiking activity in the locust tritocerebral commissure giants (TCG, a pair of identified interneurons that relay input from head hair receptors to thoracic motor centers) was found to be weaker in solitary locusts compared to gregarious ones. The solitary locusts' TCG also demonstrated much stronger spike frequency adaptation in response to wind stimuli. Although the number of forehead wind sensitive hairs was found to be larger in solitary locusts, the stimuli conveyed to their flight motor centers were weaker. The tritocerebral commissure dwarf (TCD) is an inhibitory flight‐related interneuron in the locust that responds to light stimuli. An increase in TCD spontaneous activity in dark conditions was significantly stronger in gregarious locusts than in solitary ones. Thus, phase‐dependent differences in the activity of flight‐related interneurons reflect behavioral phase characteristics. © 2003 Wiley Periodicals, Inc. J Neurobiol 57: 152–162, 2003
Specification of motoneuron fate in Drosophila: Integration of positive and negative transcription factor inputs by a minimal eve enhancer
Authors: McDonald Jocelyn A. , Fujioka Miki , Odden Joanne P. , Jaynes James B. , Doe Chris Q.
Published: October 2003

We are interested in the mechanisms that generate neuronal diversity within the Drosophila central nervous system (CNS), and in particular in the development of a single identified motoneuron called RP2. Expression of the homeodomain transcription factor Even‐skipped (Eve) is required for RP2 to establish proper connectivity with its muscle target. Here we investigate the mechanisms by which eve is specifically expressed within the RP2 motoneuron lineage. Within the NB4‐2 lineage, expression of eve first occurs in the precursor of RP2, called GMC4‐2a. We identify a small 500 base pair eve enhancer that mediates eve expression in GMC4‐2a. We show that four different transcription factors (Prospero, Huckebein, Fushi tarazu, and Pdm1) are all expressed in GMC4‐2a, and are required to activate eve via this minimal enhancer, and that one transcription factor (Klumpfuss) represses eve expression via this element. All four positively acting transcription factors act independently, regulating eve but not each other. Thus, the eve enhancer integrates multiple positive and negative transcription factor inputs to restrict eve expression to a single precursor cell (GMC4‐2a) and its RP2 motoneuron progeny. © 2003 Wiley Periodicals, Inc. J Neurobiol 57: 193–203, 2003
Balance of cell proliferation and death among dynamic populations: A mathematical model
Authors: Miller Michael W.
Published: October 2003

Developmental changes in cell numbers represent the dynamic balance between cell proliferation and death. One obstacle to assessing this balance is an inability to quantify the total amount of cell death, i.e., with a positive indicator such as terminal dUTP nick end labeling (TUNEL) or caspase activity. A novel mathematical model is described wherein data on daily cell growth (the change in cell number) and cell cycle kinetics can be used to determine the total amount of cell death. Two sets of data from previously published studies were tested in this model; primary cultured cortical neurons and B104 neuroblastoma cells. These two preparations have contrasting features: neuronal cultures are heterogeneous and have relatively few cells that are actively cycling (i.e., the growth fraction for these cells is low), whereas B104 cells are relatively homogeneous cultures in which the growth fraction is high. In primary cortical cultures, there was a balance in cell production and death. Treatment with a potent anti‐mitogen, ethanol (400 mg/dl), affected this balance principally by reducing cell production, although the rate of cell death was also increased. In untreated B104 cells, there was eight‐fold more cell production than cell death. Growth factors such as platelet‐derived growth factor BB doubled cell production. Ethanol reduced cell production by >60%, and it eliminated growth factor‐mediated cell production. All of these changes occurred in the absence of an effect on the amount of cell death. Thus, the model is ideal for predicting the effects of an epigenetic factor (e.g., a growth factor, toxin, or pharmacological agent) on cell development and can be useful in determining the consequences of a genetic manipulation as well. © 2003 Wiley Periodicals, Inc. J Neurobiol 57:172–182, 2003
Rapid electrical and delayed molecular signals regulate the serum response element after nerve injury: Convergence of injury and learning signals
Authors: Lin Hana , Bao Jianxin , Ying Ju‐Sung , Walters Edgar T. , Ambron Richard T.
Published: October 2003

Axotomy elicits changes in gene expression, but little is known about how information from the site of injury is communicated to the cell nucleus. We crushed nerves in Aplysia californica and the sciatic nerve in the mouse and found short‐ and long‐term activation of an Elk1‐SRF transcription complex that binds to the serum response element (SRE). The enhanced short‐term binding appeared rapidly and was attributed to the injury‐induced activation of an Elk1 kinase that phosphorylates Elk1 at ser383. This kinase is the previously described Aplysia (ap) ERK2 homologue, apMAPK. Nerve crush evoked action potentials that propagated along the axon to the cell soma. Exposing axons to medium containing high K+, which evoked a similar burst of spikes, or bathing the ganglia in 20 μM serotonin (5HT) for 20 min, activated the apMAPK and enhanced SRE binding. Since 5HT is released in response to electrical activity, our data indicate that the short‐term process is initiated by an injury‐induced electrical discharge that causes the release of 5HT which activates apMAPK. 5HT is also released in response to noxious stimuli for aversive learning. Hence, apMAPK is a point of convergence for injury signals and learning signals. The delay before the onset of the long‐term SRE binding was reduced when the crush was closer to the ganglion and was attributed to an Elk1 kinase that is activated by injury in the axon and retrogradely transported to the cell body. Although this Elk1 kinase phosphorylates mammalian rElk1 at ser383, it is distinct from apMAPK. © 2003 Wiley Periodicals, Inc. J Neurobiol 57: 204–220, 2003
Non‐reflecting artificial boundaries for transient scalar wave propagation in a two‐dimensional infinite homogeneous layer
Authors: Zhao Chongbin , Liu Tianyun
Published: October 2003

This paper presents an exact non‐reflecting boundary condition for dealing with transient scalar wave propagation problems in a two‐dimensional infinite homogeneous layer. In order to model the complicated geometry and material properties in the near field, two vertical artificial boundaries are considered in the infinite layer so as to truncate the infinite domain into a finite domain. This treatment requires the appropriate boundary conditions, which are often referred to as the artificial boundary conditions, to be applied on the truncated boundaries. Since the infinite extension direction is different for these two truncated vertical boundaries, namely one extends toward x →∞ and another extends toward x→‐ ∞, the non‐reflecting boundary condition needs to be derived on these two boundaries. Applying the variable separation method to the wave equation results in a reduction in spatial variables by one. The reduced wave equation, which is a time‐dependent partial differential equation with only one spatial variable, can be further changed into a linear first‐order ordinary differential equation by using both the operator splitting method and the modal radiation function concept simultaneously. As a result, the non‐reflecting artificial boundary condition can be obtained by solving the ordinary differential equation whose stability is ensured. Some numerical examples have demonstrated that the non‐reflecting boundary condition is of high accuracy in dealing with scalar wave propagation problems in infinite and semi‐infinite media. Copyright © 2003 John Wiley & Sons, Ltd.
An accurate scheme for mixed‐mode fracture analysis of functionally graded materials using the interaction integral and micromechanics models
Authors: Kim Jeong‐Ho , Paulino Glaucio H.
Published: October 2003

The interaction integral is a conservation integral that relies on two admissible mechanical states for evaluating mixed‐mode stress intensity factors (SIFs). The present paper extends this integral to functionally graded materials in which the material properties are determined by means of either continuum functions (e.g. exponentially graded materials) or micromechanics models (e.g. self‐consistent, Mori–Tanaka, or three‐phase model). In the latter case, there is no closed‐form expression for the material‐property variation, and thus several quantities, such as the explicit derivative of the strain energy density, need to be evaluated numerically (this leads to several implications in the numerical implementation). The SIFs are determined using conservation integrals involving known auxiliary solutions. The choice of such auxiliary fields and their implications on the solution procedure are discussed in detail. The computational implementation is done using the finite element method and thus the interaction energy contour integral is converted to an equivalent domain integral over a finite region surrounding the crack tip. Several examples are given which show that the proposed method is convenient, accurate, and computationally efficient. Copyright © 2003 John Wiley & Sons, Ltd.
Hybrid‐stabilized solid‐shell model of laminated composite piezoelectric structures under non‐linear distribution of electric potential through thickness
Authors: Yao Lin Quan , Lu Li
Published: October 2003

Eighteen‐node solid‐shell finite element models have been developed for the analysis of laminated composite plate/shell structures embedded with piezoelectric actuators and sensors. The explicit hybrid stabilization method is employed to formulate stabilization vectors for the uniformly reduced integrated 18‐node three‐dimensional composite solid element. Unlike conventional piezoelectric elements, the concept of the electric nodes introduced in this paper can effectively eliminate the burden of constraining the equality of the electric potential for the nodes lying on the same electrode. Furthermore, the non‐linear distribution of electric potential in the piezoelectric layer is expressed by introducing internal electric potential, which not only can simplify modelling but also obtains the same as the exact solution. Copyright © 2003 John Wiley & Sons, Ltd.
Implicit integration and consistent tangent modulus of a time‐dependent non‐unified constitutive model
Authors: Kobayashi M. , Mukai M. , Takahashi H. , Ohno N. , Kawakami T. , Ishikawa T.
Published: October 2003

This paper describes the implicit integration and consistent tangent modulus of an inelastic constitutive model with transient and steady strain rates, both of which are time‐ and temperature‐dependent; the transient rate is influenced by the evolution of back stress decomposed into parts, while the steady rate depends only on applied stress and temperature. Such a non‐unified model is useful for high‐temperature structural analysis and is practical owing to the ease in determining material constants. The implicit integration is shown to result in two scalar‐valued coupled equations, and the consistent tangent modulus is derived in a quite versatile form by introducing a set of fourth‐rank constitutive parameters into the discretized evolution rule of back stress. The constitutive model is, then, implemented in a finite element program and applied to a lead‐free solder joint analysis. It is demonstrated that the implicit integration is very accurate if the multilinear kinematic hardening model of Ohno and Wang is employed, and that the consistent tangent modulus certainly affords quadratic convergence to the Newton–Raphson iteration in solving nodal force equilibrium equations. Copyright © 2003 John Wiley & Sons, Ltd.
Multi‐time‐step and two‐scale domain decomposition method for non‐linear structural dynamics
Authors: Gravouil A. , Combescure A.
Published: October 2003

In this paper we propose a method to improve the means of taking into account the specific time‐scale and space‐scale characteristics in time‐dependent non‐linear problems. This method enables the use of arbitrary time steps in each subdomain: these can be coupled by prescribing continuous velocities at the interfaces, which are modelled using a dual Schur formulation. For certain subdomains, in space, we adopt a two‐scale resolution technique inspired by the multigrid methods in order to obtain the part of the solution related to small variation lengths on a refined scale and the part corresponding to large variation lengths on a coarse scale. For non‐linear problems, we propose an algorithm with a single iteration level to deal with both the non‐linear equilibrium and the two space scales thanks to a two‐grid method in which the relaxation steps are performed using a non‐linear, preconditioned conjugate gradient algorithm. Finally, we present an example which demonstrates the feasibility of the method. Copyright © 2003 John Wiley & Sons, Ltd.
Vector level sets for description of propagating cracks in finite elements
Authors: Ventura G. , Budyn E. , Belytschko T.
Published: October 2003

A new level set method is developed for describing surfaces that are frozen behind a moving front, such as cracks. In this formulation, the level set is described in two dimensions by a three‐tuple: the sign of the level set function and the components of the closest point projection to the surface. The update of the level set is constructed by geometric formulas, which are easily implemented. Results are given for growth of lines in two dimensions that show the method is very accurate. The method combines very naturally with the extended finite element method (XFEM) where the discontinuous enrichment for cracks is best described in terms of level set functions. Examples of crack growth simulations obtained by combining this level set method with the extended finite element method are given. Copyright © 2003 John Wiley & Sons, Ltd.
Measuring decentralisation: the case of Kerala (India)
Authors: John M. S. , Chathukulam Jos
Published: October 2003

Attempts at measuring decentralisation are still in an underdeveloped stage. The reason for this lies in the failure to devise common standards against which measurement is possible and the lack of consensus about the very meaning of decentralisation. An attempt to measure decentralisation was made by Vengroff and Ben Salem in the context of Tunisia nearly a decade ago. An expanded and adapted version of this model is used to measure decentralisation in Kerala using the same judgmental criteria that they used after involving a panel of nine experts. These experts had a fairly good understanding of the practice of decentralisation to score on the basis of the adapted criteria. An ideal form of decentralisation envisaged in this measurement exercise is devolution. It has been found that on a scale ranging between 0 and 5, the state of Kerala obtained a score of 2.00 in spite of the fact that the investment that the state had made in decentralisation has no parallels anywhere in the developing countries. Such a low score, despite the much publicised campaign for decentralisation, was due to the focus on planning rather than on decentralisation issues. Attempts to measure decentralisation will not only enable us to develop more contextually valid measures of decentralisation, but also contribute to the clarification of the concept of decentralisation, particularly by identifying aspects neglected hitherto. Copyright © 2003 John Wiley & Sons, Ltd.
Partnerships between local governments and community‐based organisations: exploring the scope for synergy
Authors: Krishna Anirudh
Published: October 2003

The utility of both local governments and community‐based organisations can be considerably enhanced when these agencies work in partnership with one another. Different roles will be played by local governments and community organisations in different types of partnership arrangements. Distinguishing among these roles helps allocate responsibilities better among the partner agencies, and it is also helpful for scheduling implementation, devising appropriate capacity building programmes and designing suitable accountability mechanisms. An analytical framework to help with these tasks is developed and presented in this article. Copyright © 2003 John Wiley & Sons, Ltd.
Local government decision‐making—citizen participation and local accountability: some evidence from Kenya and Uganda
Authors: Devas Nick , Grant Ursula
Published: October 2003

The current fashion for decentralisation is built on the assumption that it will result in decisions that reflect local needs and priorities. Yet representative democracy, through periodic elections, is a crude mechanism for establishing these needs and priorities. Most local government systems offer few other opportunities for citizens to participate, particularly for the poor, and few mechanisms of accountability. This article reviews the literature relating local level decision‐making, citizen participation and accountability. It then presents the findings of a study of decision‐making about the use of resources in a sample of municipal governments in Kenya and Uganda. Local governments in Kenya have traditionally offered minimal scope for citizen participation or accountability, but this is beginning to change, mainly as a result of performance conditions applied through the recently introduced Local Authorities Transfer Fund (LATF), together with an increasingly active civil society. In Uganda, which has undergone a radical decentralisation, there is much greater scope for citizen participation at the local level but there are still many of the same problems of local accountability as in Kenya. The article reviews some of the examples of, and reasons for, good (and bad) practice. It concludes that factors like committed local leadership, central monitoring of performance, articulate civil society organisations and the availability of information are critical. But even with these, there is no guarantee that decentralised decision‐making will be inclusive of the poor. Copyright © 2003 John Wiley & Sons, Ltd.
An introduction to Decentralized Cooperation: definitions, origins and conceptual mapping
Authors: Hafteck Pierre
Published: October 2003

The term ‘Decentralized Cooperation’, coined in the 1980s, is interpreted differently by various organisations involved in development cooperation. However, there are points of convergence among these interpretations that suggest a common definition involving: (a) the lead actors (local governments), (b) an overarching objective (sustainable local development) and (c) the nature of activities carried out (exchanges and support). From a historical perspective, the origin of Decentralized Cooperation is two‐fold. On the development cooperation scene, the concept emerged when the array of actors involved in development projects widened as a result of major changes in aid themes and approaches. In the field of international relations between local governments, Decentralized Cooperation activities appeared as the scope of municipal twinnings also widened accordingly to involve partners from countries in development or in transition. Today, Decentralized Cooperation continues as an evolving concept located at the intersection of its two parent fields: development cooperation and international municipal relations. At this intersection, a fusion of experiences, resources and ideas is taking place. Copyright © 2003 John Wiley & Sons, Ltd.
The National Integrity System: assessing corruption and reform
Authors: Doig Alan , McIvor Stephanie
Published: October 2003

This article builds on a Transparency International (TI)‐sponsored research study funded by the Dutch Government into the National Integrity System (NIS) in practice. The NIS is a framework approach developed by TI that proposes assessing corruption and reform holistically. The NIS not only looks at separate institutions or separate areas of activity or separate rules and practices, but also bases its perspective on institutional and other inter‐relationships, inter‐dependence and combined effectiveness. The study involved 18 countries, using in‐country researchers and an overview report. This article assesses the findings of the study to consider how the approach can work in practice, and what the approach can reveal about the causes and nature of corruption as well as the implications for reform. Copyright © 2003 John Wiley & Sons, Ltd.
Another lost decade? The future of reform in Latin America
Authors: Santiso Carlos
Published: October 2003

The 1990s ended equivocally in Latin America. What has gone wrong? Is economic failure the cause or the consequence of the democratic decay and the erosion of governance throughout the region? The review essay revisits the debate on the intricate links between politics and economics in the second stage of reform. Moving beyond standard typologies of regime type, it explores the interactions between the quality of democratic governance and the performance of economic policy under democratic auspices, in particular its credibility. It is now amply recognized that reforms have been hindered by inefficient unreliable and unaccountable government institutions. Furthermore, the manner in which market reforms have been implemented has undermined governance and accountability. The importance of policy credibility has essentially been neglected as a pivotal condition for effective economic reform. Consequently, policymakers propose a new round of reforms, centring on strengthening the institutions of governance and modifying the incentives shaping public policy. The essay argues that restoring the credibility of policy requires a fundamental redefinition of the state and reforming the methods of government and the styles of policymaking. The defining challenge of Latin American countries is to strengthen capacity to adequately implement policy and credibly commit to policy reform. Copyright © 2003 John Wiley & Sons, Ltd.
Cryptic 1p36.3/6q25.2 translocation in three generations ascertained through a foetus with IUGR and cerebral malformations
Authors: Cavani S. , Perfumo C. , Faravelli F. , Malacarne M. , Sogliani M. , Piombo G. , Zerega G. , Zucca M. , Dagna Bricarelli F. , Pierluigi M.
Published: October 2003

Here we describe a foetus with intrauterine growth retardation (IUGR), cerebral malformations and a 46,XY,der(1),t(1;6)(p36.3;q25.2) karyotype owing to a familial cryptic translocation segregating in three generations. A balanced translocation was present in the mother, the maternal uncle, the aunt and the grandmother. A female first cousin with dysmorphisms, hydrocephalus and mental retardation was a carrier of a partial trisomy 1p and a partial monosomy 6q. Multiple miscarriages were present in the family pedigree. Parents of the foetus had three other pregnancies: a male with a balanced translocation, and two foetuses with 1p36.3–pter monosomy and 6q25.2–qter trisomy. Copyright © 2003 John Wiley & Sons, Ltd.
Craniofacial dysmorphology and three‐dimensional ultrasound: a prospective study on practicability for prenatal diagnosis
Authors: Mangione Raphaele , Lacombe Didier , Carles Dominique , Guyon Frédéric , Saura Robert , Horovitz Jacques
Published: October 2003

Objective

The aim of this study is to compare two‐dimensional and three‐dimensional ultrasound for the visualization and diagnosis of craniofacial dysmorphism.

Methods

In this prospective study, we performed three‐dimensional (3D) ultrasound following good‐quality two‐dimensional (2D) ultrasound in an at‐risk population. Findings from 2D and 3D examination were noted.

Results

Our series included 41 patients. In 20 cases, 3D performed better than 2D, and in two cases 2D was more informative. In 9 cases, there was no difference between the performance of the two, and in two cases both 2D and 3D gave inadequate results. However, in 7 cases 3D images could not be obtained.

Conclusion

Although it is rarely decisive, 3D ultrasound is of interest when it comes to the precise description of craniofacial dysmorphisms and the study of the fetal ears. Copyright © 2003 John Wiley & Sons, Ltd.
The use of record linkage for auditing the uptake and outcome of prenatal serum screening and prenatal diagnostic tests for Down syndrome
Authors: Alberman Eva , Huttly Wayne , Hennessy Enid , McIntosh Alan
Published: October 2003

Objectives

To pilot the use of linked routine records for auditing Down syndrome prenatal serum screening and diagnostic tests.

Methods

The cohort studied were 110 272 patients of 4 London maternity units that offered the Bart's maternal serum tests any time between 1990 and 1999. Audit was based on linked data derived from obstetric records, referral data on maternal serum screening and/or prenatal diagnoses. Cytogenetic reports without matching obstetric data were retained in the cohort as they included fetal deaths or terminations.

Results

(1) Significant independent influences on uptake of serum screening (58% overall) were maternal age, ethnicity, year and referring hospital, and those on uptake of prenatal diagnosis (4% overall) were screening result (54% uptake after positive screen), maternal age, year and referring hospital; (2) detection, false‐positive rates and odds of being affected after positive results were respectively 49%, 4% and 1 : 59 between 1990 and 1994, and 78%, 7% and 1 : 58 after 1994. Using maternal age alone (cut‐off ≥37 at delivery), these would have been respectively 40%, 7% and 1 : 96 between 1990 and 1994, and 40%, 9% and 1 : 107 between 1995 and 1999.

Conclusions

Ongoing audit of DS prenatal programmes could be derived from computerised maternity data sets if they included fetal deaths, and relevant laboratory and ultrasound findings. Copyright © 2003 John Wiley & Sons, Ltd.
Intracranial hemorrhage progressing to porencephaly as a result of congenitally acquired cytomegalovirus infection—an illustrative report
Authors: Moinuddin Asif , McKinstry Robert C. , Martin Kimberly A. , Neil Jeffrey J.
Published: October 2003

Objective

To report ultrasound and magnetic resonance imaging (MRI) findings in a fetus with intracranial hemorrhage and porencephaly, presumed secondary to intrauterine cytomegalovirus (CMV) infection.

Methods

A 20‐year‐old, G2, P1 woman presented at 28.6 weeks' gestation after ultrasound examination demonstrated apparently isolated fetal ascites. Evaluation included maternal serology, amniocentesis, and repeated ultrasound examinations. Fetal MRI evaluation was also performed. The infant was born at 35 weeks' gestational age.

Results

Maternal serology was positive for CMV IgG. Intrauterine CMV infection was confirmed using polymerase chain reaction (PCR). At 31.6 weeks' gestation, ultrasound demonstrated borderline lateral cerebral ventriculomegaly. MRI of the fetal brain on the same day demonstrated parenchymal hemorrhage in the right posterior temporal and parietal regions along with mild ventricular enlargement. Sonography one day before delivery revealed brain parenchymal cystic change consistent with porencephaly of the right posterior temporal and parietal region. Postnatal ultrasound, computed tomography (CT), and MRI confirmed the diagnosis of a porencephalic cyst communicating with the posterior body of the right lateral ventricle. Placental pathology was consistent with CMV infection.

Conclusion

This case report illustrates that fetal MRI is a useful adjunct in the evaluation of intrauterine infection with CMV. Copyright © 2003 John Wiley & Sons, Ltd.
Ethmocephaly caused by de novo translocation 18;21—prenatal diagnosis
Authors: Goldstein Israel , Weissman Amir , Brill‐Zamir Ronit , Laevsky Ilana , Drugan Arie
Published: October 2003

Ethmocephaly is a rare anomaly associated with partial failure of cleavage of the prosencephalon. Morphologically, it is closely related to cyclopia. We present an extremely rare case of ethmocephaly diagnosed in utero and caused by an unbalanced de novo translocation 18;21. Copyright © 2003 John Wiley & Sons, Ltd.
Ultrasound evaluation of fetal nasal bone at 11 to 14 weeks in a consecutive series of 1906 fetuses
Authors: Viora E. , Masturzo B. , Errante G. , Sciarrone A. , Bastonero S. , Campogrande M.
Published: October 2003

Objective

The aim of this study is to evaluate the significance of nasal bone ossification as a marker for trisomy 21 at 11 to 14 weeks' gestation in an unselected obstetric population referred to our Centre.

Methods

A total of 1906 consecutive fetuses undergoing nuchal translucency scan at 11 to 14 weeks' gestation were evaluated for the presence of hypoplasia/absence of nasal bone. The data obtained were correlated with fetal karyotype.

Results

A successful view of the fetal profile was obtained in 1752 fetuses (91.9%). The nasal bone was hypoplastic/absent in 12 of 19 fetuses with chromosomal abnormalities. There were 10 cases of trisomy 21, in 8 of which hypoplastic/absent nasal bone was observed. Furthermore, absence of nasal bone was recorded in 24 of 1733 chromosomally normal fetuses.

Conclusions

Nasal bone evaluation may improve the detection of trisomy 21 in the first trimester in an unselected obstetric population. Although numerically limited, our experience confirms that delayed nasal bone ossification (hypoplasia/absence of nasal bone) is rarely observed in chromosomally normal fetuses (1.4%). An appropriate training of operators is mandatory in order to achieve an acceptable performance. Copyright © 2003 John Wiley & Sons, Ltd.
Prenatal diagnosis of capillary telangiectasia of the cerebellum—ultrasound and MRI features
Authors: Guibaud Laurent , Garel Catherine , Annie Buenerd , Pascal Gaucherand , François Varlet , Vavasseur Chantal , Oury Jean‐François , Pracros Jean‐Pierre
Published: October 2003

Objective

To report three cases of capillary telangiectasia (CT) of the cerebellum revealed as focal cerebellar lesions.

Methods

Ultrasound and magnetic resonance imaging (MRI) were performed in all cases in the prenatal period. Prenatal imaging findings were compared with either post‐mortem examination (case 1) or post‐natal MRI (cases 2 & 3).

Results

A discrepancy between a hyperechoic lesion without any mass effect on sonogram and normal T1 and T2 spin‐echo fetal magnetic resonance images was found in all cases. The diagnosis of CT was made on post‐mortem examination in case 1. Prenatal ultrasound and magnetic resonance imaging findings were suggestive of the diagnosis in cases 2 and 3. In both cases, the pregnancy was managed conservatively and the diagnosis of CT was documented on post‐natal MRI after gadolinium injection.

Conclusion

The diagnosis of CT of the cerebellum was strongly suggested in these three cases in the prenatal period by the combination of ultrasound and fetal MRI findings. In the vast majority of cases, CT has a benign clinical course and complication with haemorrhage appears to be exceedingly rare. This fact should be taken into account in the prenatal counselling. Copyright © 2003 John Wiley & Sons, Ltd.
Prenatal diagnosis of cavum velum interpositum cysts: significance and outcome
Authors: Eisenberg Vered H. , Zalel Yaron , Hoffmann Chen , Feldman Zeev , Achiron Reuwen
Published: October 2003

Objectives

To describe a fetal cavum velum interpositum cyst (CVIC) and to review its clinical significance.

Methods

Description and follow‐up of two cases with prenatal diagnosis of a midline cyst in the fetal brain, at the Chaim Sheba Medical Center. The cases were reviewed and followed‐up by a multidisciplinary team that included sonographers, pediatric neurologists, pediatric neurosurgeons, radiologists, and clinical geneticists. Medline search of cases of cysts of the cavum velum interpositum as reported in the English literature.

Results

Two patients referred for consultation owing to midline cysts were diagnosed with isolated cysts of the cavum velum interpositum without other anomalies. Magnetic resonance imaging (MRI) of the fetal brain did not reveal any additional malformations in either case. Prenatal follow‐up showed the cysts to be stable in one case and decreased in size in the other. Postnatal neurodevelopmental outcome to date is normal. (Range of follow‐up: 6–24 months.) Eight cases reported in the literature as CVIC resulted in favorable prognosis in all without further intervention. However, one infant required ventriculoperitoneal shunting due to progressive hydrocephalus, but developed normally nonetheless.

Conclusion

Prenatal diagnosis of cysts of the cavum velum interpositum, which are isolated, single, stable in size, and not associated with other anomalies, is consistent with a favorable postnatal outcome. Copyright © 2003 John Wiley & Sons, Ltd.
First‐trimester screening for Down syndrome in France combining fetal nuchal translucency measurement and biochemical markers
Authors: Muller Françoise , Benattar Clarisse , Audibert François , Roussel Nathalie , Dreux Sophie , Cuckle Howard
Published: October 2003

Background

In France, there is a strictly regulated National Screening Programme for Down syndrome, based on second‐trimester maternal serum markers. A prospective study of nuchal translucency together with retrospective evaluation of maternal serum markers was carried out to inform decisions on whether to move the programme to the first trimester.

Methods

Between January 1998 and June 2001, all women who presented for their prenatal care at 12 participating maternity units were, regardless of age, invited to provide a blood sample and to attend for an NT scan at 11 to 13 weeks. The results were used to derive Gaussian distribution parameters. Detection and false‐positive rates were computed in two ways: statistical modelling and directly. The cut‐off risk was 1 in 250 at term.

Results

A total of 5694 women with singleton pregnancies were screened including 26 with Down syndrome and 24 with other aneuploidies. The model‐predicted detection and false‐positive rates for combined ultrasound and serum screening were 81 and 4.5% compared to 64 and 6.0% for ultrasound alone. The directly observed rates were 73 and 4.7%, compared to 62 and 5.0% respectively.

Conclusion

In France, first‐trimester screening with nuchal translucency and maternal serum markers is likely to achieve a high screening efficiency. This has important implications for the national screening policy. Copyright © 2003 John Wiley & Sons, Ltd.
Do women prefer to have screening tests for Down syndrome that have the lowest screen‐positive rate or the highest detection rate?
Authors: Mulvey Sheila , Zachariah Rebecca , McIlwaine Kate , Wallace Euan M.
Published: October 2003

Objective

To assess whether women have a preference for Down syndrome screening test performance.

Methods

A structured questionnaire exploring women's preferences for screening test performance was administered to women attending their first prenatal visit who wished to have Down syndrome screening performed.

Results

One hundred and twenty women were interviewed. The majority of women (n = 80) chose a screening test with a low screen‐positive rate rather than the highest detection rate. The reasons given for this preference were a desire to minimise the risk of miscarriage of a normal baby and a belief that a detection rate of 80 to 90% was acceptable. However, older women (>37 years) chose a test with the highest detection rate possible, regardless of the higher screen‐positive rate, preferring to miscarry a normal baby as a result of a diagnostic test rather than miss the detection of a baby with Down syndrome. Preferences were not influenced by previous screening experience.

Conclusions

Women express different preferences for screening test performance. Maternal age rather than previous screening experiences appears to be the major influence in these choices. Copyright © 2003 John Wiley & Sons, Ltd.
Fetal cells and DNA in maternal blood
Authors: Jackson Laird
Published: October 2003

Although fetal cells have been known to escape to the maternal circulation for a number of years, research attempts to use them for prenatal diagnosis have not had any consistent success. This review attempts to trace the history of such attempts and to document their progress and reasons for success or failure. The opinions of recent conferences including that of the US National Institute of Child Health and Human Development, a sponsor of major US research in the field, are reported and discussed. It is concluded that although basic work has demonstrated the biologic availability of both fetal cells and their free DNA representatives in the maternal circulation at gestational ages relevant to prenatal diagnosis, much work remains to develop practical technology for their consistent recovery and assay. Copyright © 2003 John Wiley & Sons, Ltd.
Fetal chromosomal analysis of pregnancies following intracytoplasmic sperm injection with amniotic tissue culture
Authors: Samli Hale , Solak Mustafa , Imirzalioǧlu Necat , Beyatlı Yavuz , Şimşek Solmaz , Kahraman Semra
Published: October 2003

Objectives

The objective of this study was to determine the incidence of chromosomal anomalies in a complete cohort of ICSI pregnancies.

Methods

From January 1996 to December 2000, 1500 consecutive patients who had become pregnant after Intracytoplasmic Sperm Injection (ICSI) were given prenatal genetic counseling and 98 of them (6.5%) who accepted amniocentesis were studied. Amniocentesis was performed between 14 and 20th weeks of their pregnancy. Amniotic tissue cultures were processed according to Hoehn et al. A minimum of 20 metaphases were examined on each preparation. Both parents were also evaluated with peripheral blood karyotyping.

Results

Amniocentesis and karyotyping was performed to evaluate the 142 fetuses from 98 ICSI pregnancies. Karyotypes from peripheral leucocytes of the parents were also evaluated. Chromosomal anomalies were detected from 6 out of the 142 (4.2%) fetuses. The anomalies were as follows, ‘46,XX/69,XXX/92,XXXX’, ‘46,XY/69,XXY/92,XXYY’, ‘47,XY + 21’, ‘46,XY/47,XY + 7’, ‘47,XXY’, and ‘45,X0’. All except one pregnancy were terminated with the consent of the couples. Fetal tissue cultures were also studied after the termination of the pregnancy in order to confirm prenatal diagnosis. We did not detect abnormal karyotype from the parents of these fetuses.

Conclusions

The ratio of chromosomal abnormalities seems to be slightly increased in ICSI pregnancies. Paternal factors due to morphologically abnormal spermatozoa, maternal factors due to increased mother age and more frequently, de novo occurring sex chromosomal abnormalities may be responsible for this outcome. Copyright © 2003 John Wiley & Sons, Ltd.