bluuebunny/crossref_metadata_2025 huggingface dataset:
A COMMENT ON “PRICE DISPERSION, INFLATION, AND WELFARE” BY A. HEAD AND A. KUMAR*
Authors: Mortensen Dale T.
Published: May 2005

The principal results of Head and Kumar's article are derived under the natural assumption that the number of price offers received per period by buyers is distributed Poisson. This case is of interest for two reasons. First, because the infinite sums and integrals that enter the equilibrium conditions can be solved in closed form, the derivations of the model's implications are straightforward. Second, by regarding the arrival rate as the relevant measure of search intensity, the analysis of endogenous search effort is simplified.
FROM PRIVATE BANKING TO CENTRAL BANKING: INGREDIENTS OF A WELFARE ANALYSIS*
Authors: Wallace Neil
Published: May 2005

An earlier analysis of Cavalcanti and Wallace showing that the set of allocations achievable using outside (government) money is a subset of those achievable using inside (private) money is extended. Here, the class of outside‐money allocations is enriched by allowing the planner to make transfers in the form of outside money. At the same time, punishments for defection are weakened. It is shown that the subset result continues to hold, although for a different reason than in the Cavalcanti and Wallace analysis.
OPTIMAL MONETARY POLICY: WHAT WE KNOW AND WHAT WE DON'T KNOW*
Authors: Kocherlakota Narayana R.
Published: May 2005

In this article, I examine the current state of knowledge about optimal monetary policy. I distinguish between two literatures, basic and applied. The basic literature is explicit about the frictions that generate a positive value for money and make it socially beneficial. The applied literature is not. I describe the recent lessons about monetary policy that we have learned from each literature and discuss how the two distinct approaches may be usefully combined.
Analysis of the Residual Stress around a Cold‐expanded Fastener Hole in a Finite Plate
Authors: Zhang Y. , Fitzpatrick M. E. , Edwards L.
Published: May 2005

Abstract:  In this paper, we present results of residual stresses around a cold‐worked fastener hole in a thin, finite plate. An analytical model, with plane stress conditions, elastic nonlinear–plastic loading and unloading taken into account, is explicitly presented and has been developed from existing analytical models and methodologies. The solution also accounts for elastic deformation of the mandrel, and is applicable to different sizes of hole and mandrel. A parametric study of the strain‐hardening exponent, plate size, Bauschinger parameter and expansion ratio was carried out in the context of the present solution. A sample study of a plate subjected to 4% hole‐cold expansion was performed to compare this model with other analytical predictions, finite element simulation and X‐ray diffraction experimental results. A brief review of related issues is given. This work is intended to present completely the closed‐form equations able to generate residual stress profiles with ease around a cold‐expanded hole in a thin, finite plate where boundary conditions are at issue.
Diverse developmental mechanisms contribute to different levels of diversity in horned beetles
Authors: Moczek Armin P. , Nagy Lisa M.
Published: May 2005

Summary
An ongoing challenge to evolutionary developmental biology is to understand how developmental evolution on the level of populations and closely related species relates to macroevolutionary transformations and the origin of morphological novelties. Here we explore the developmental basis of beetle horns, a morphological novelty that exhibits remarkable diversity on a variety of levels. In this study, we examined two congeneric Onthophagus species in which males develop into alternative horned and hornless morphs and different sexes express marked sexual dimorphism. In addition, both species differ in the body region (head vs. thorax) that develops the horn. Using a comparative morphological approach we show that prepupal growth of horn primordia during late larval development, as well as reabsorption of horn primordia during the pupal stage, contribute to horn expression in adults. We also show that variable combinations of both mechanisms are employed during development to modify horn expression of different horns in the same individual, the same horn in different sexes, and different horns in different species. We then examine expression patterns of two transcription factors, Distal‐less (Dll) and aristaless (al), in the context of prepupal horn growth in alternative male morphs and sexual dimorphisms in the same two species. Expression patterns are qualitatively consistent with the hypothesis that both transcription factors function in the context of horn development similar to their known roles in patterning a wide variety of arthropod appendages. Our results suggest that the origin of morphological novelties, such as beetle horns, rests, at least in part, on the redeployment of already existing developmental mechanisms, such as appendage patterning processes. Our results also suggest, however, that little to no phylogenetic distance is needed for the evolution of very different modifier mechanisms that allow for substantial modulation of trait expression at different time points during development in different species, sexes, or tissue regions of the same individual. We discuss the implications of our results for our understanding of the evolution of horned beetle diversity and the origin and diversification of morphological novelties.
vasa and nanos expression patterns in a sea anemone and the evolution of bilaterian germ cell specification mechanisms
Authors: Extavour Cassandra G. , Pang Kevin , Matus David Q. , Martindale Mark Q.
Published: May 2005

Summary
Most bilaterians specify primordial germ cells (PGCs) during early embryogenesis using either inherited cytoplasmic germ line determinants (preformation) or induction of germ cell fate through signaling pathways (epigenesis). However, data from nonbilaterian animals suggest that ancestral metazoans may have specified germ cells very differently from most extant bilaterians. Cnidarians and sponges have been reported to generate germ cells continuously throughout reproductive life, but previous studies on members of these basal phyla have not examined embryonic germ cell origin. To try to define the embryonic origin of PGCs in the sea anemone Nematostella vectensis, we examined the expression of members of the vasa and nanos gene families, which are critical genes in bilaterian germ cell specification and development. We found that vasa and nanos family genes are expressed not only in presumptive PGCs late in embryonic development, but also in multiple somatic cell types during early embryogenesis. These results suggest one way in which preformation in germ cell development might have evolved from the ancestral epigenetic mechanism that was probably used by a metazoan ancestor.
A delay in age at first mating results in the loss of future reproductive potential via apoptosis
Authors: Moore Patricia J. , Sharma Simone
Published: May 2005

Summary
Women who delay childbearing risk subfertility. However, this loss of fertility is not a simple function of aging. Women who have had children early in life tend to maintain fertility longer, measured as a later age at menopause. But why should otherwise healthy women lose reproductive capacity? Loss of fertility independent of senescence, menopause, has been approached from two perspectives: evolution and development. Evolutionary biologists focus on how natural selection favors survival after reproductive ability has ceased, whereas reproductive biologists examine mechanisms by which women lose fertility with age and factors that influence the rate of reproductive aging. Combining mechanistic studies with evolutionary theory should allow us to define principles of the evolution of postembryonic development of ovaries, including the role of reproductive timing relative to sexual maturation. Achieving this will require identifying appropriate, and more experimentally tractable, taxa in which to study how early reproductive events influence lifetime fertility. We work with an invertebrate species, the cockroach Nauphoeta cinerea, with a complex reproductive biology in which females experience reproductive cycles, give live birth, and show age‐related decline in fertility. Thus, N. cinerea provides an opportunity to use an experimental approach to examine mechanisms by which females lose reproductive potential as they delay reproduction. Our results demonstrate that the loss of both oocytes ready for fertilization and future oocytes in females that delay mating is because of apoptosis. We suggest that loss of fertility because of delayed mating may originate in a nonadaptive response in control of apoptosis through mistiming of reproduction.
Quantitative trait loci mapping of floral and leaf morphology traits inArabidopsis thaliana: evidence for modular genetic architecture
Authors: Juenger Thomas , Pérez‐Pérez José Manuel , Bernal Salvador , Micol José Luis
Published: May 2005

SummaryMorphological variation within organisms is integrated and often modular in nature. That is to say, the size and shape of traits tend to vary in a coordinated and structured manner across sets of organs or parts of an organism. The genetic basis of this morphological integration is largely unknown. Here, we report on quantitative trait loci (QTL) analysis of leaf and floral organ size inArabidopsis thaliana. We evaluate patterns of genetic correlations among traits and perform whole‐genome scans using QTL mapping methods. We detected significant genetic variation for the size and shape of each floral and leaf trait in our study. Moreover, we found large positive genetic correlations among sets of either flower or leaf traits, but low and generally nonsignificant genetic correlations between flower and leaf traits. These results support the hypothesis of independent floral and vegetative modules. We consider co‐localization of QTL for different traits as support for a pleiotropic basis of morphological integration and modularity. A total of eight QTL affecting flower and three QTL affecting leaf traits were identified. Most QTL affected either floral or leaf traits, providing a general explanation for high correlations within and low correlations between modules. Only two genomic locations affected both flower and leaf growth. These results are discussed in the context of the evolution of modules, pleiotropy, and the putative homologous relationship between leaves and flowers.
Catamenial Epilepsy: The Elusive Condition
Authors: French Jacqueline A.
Published: May 2005

Frequency of Catamenial Seizure Exacerbation in Women with Localization-related Epilepsy

Herzog AG, Harden CL, Liporace J, Pennell P, Schomer DL, Sperling M, Fowler K, Nikolov B, Shuman S, Newman M

Ann Neurol 2004;56:431–434

This investigation assessed the frequency of catamenial epilepsy in 87 women who charted seizures and menses during three cycles. Catamenial epilepsy designation was made if two of three cycles showed at least one of three previously defined catamenial patterns. Among ovulatory cycles, average daily seizure frequency was significantly greater during the perimenstrual and preovulatory phases. Among anovulatory cycles, average daily seizure frequency was substantially less during the midfollicular phase than during the remainder of the cycle. Overall, 39.1% of the women had catamenial epilepsy.
H-Channels and Seizures: Less is More
Authors: Poolos Nicholas P.
Published: May 2005

Seizure-induced Plasticity of h Channels in Entorhinal Cortical Layer III Pyramidal Neurons

Shah MM, Anderson AE, Leung V, Lin X, Johnston D

Neuron 2004;44:495–508

The entorhinal cortex (EC) provides the predominant excitatory drive to the hippocampal CA1 and subicular neurons in chronic epilepsy. Discerning the mechanisms underlying signal integration within EC neurons is essential for understanding network excitability alterations involving the hippocampus during epilepsy. Twenty-four hours after a single seizure episode when no behavioral or electrographic seizures occurred, we found enhanced spontaneous activity still present in the rat EC in vivo and in vitro. The increased excitability was accompanied by a profound reduction in Ih in EC layer III neurons and a significant decline in hyperpolarization-activated cation (HCN)1 and HCN2 subunits that encode for h channels. Consequently, dendritic excitability was enhanced, resulting in increased neuronal firing despite hyperpolarized membrane potentials. The loss of Ih and the increased neuronal excitability persisted for 1 week after seizures. Our results suggest that dendritic Ih plays an important role in determining the excitability of EC layer III neurons and their associated neural networks.
Experimental Febrile Seizures Require an Undetermined Factor for Induction of Hippocampal Sclerosis in Immature Rat Brain
Authors: Pitkänen Asla , Gröhn Olli
Published: May 2005

Serial MRI after Experimental Febrile Seizures: Altered T2 Signal without Neuronal Death

Dube C, Yu H, Nalcioglu O, Baram TZ

Ann Neurol 2004;56:709–714

Whereas most febrile seizures (FSs) carry a benign outcome, a subpopulation of individuals with prolonged FSs are at risk for later temporal lobe epilepsy. Signal changes on MRI may provide early markers for changes in neuronal integrity that may promote epileptogenesis in such individuals. Here, we used serial MRIs, obtained before and at several times after experimental prolonged FSs, to determine the prevalence and distribution of signal changes on T2-weighted images and to investigate the pathologic substrates leading to these changes. Seventy-five percent of immature rats with experimental prolonged FSs had abnormal T2 signal enhancement at 24 hours, and 87.5%, at 8 days after the seizures. The altered T2 values involved the dorsal hippocampus (75%), the piriform cortex (87.5%), and the amygdala (25%). However, these changes were not accompanied by evidence of neuronal injury or death in these regions, as assessed by using the Fluoro-Jade method. Thus, experimental prolonged FSs lead to relatively frequent abnormal MRI signal in “temporal lobe” structures. Although these changes do not signify cell death, they may denote pathologic cellular processes that promote epileptogenesis.
MRI-negative Temporal Lobe Epilepsy: Is there a Role for PET?
Authors: Schwartz Theodore H.
Published: May 2005

MRI-negative PET-positive Temporal Lobe Epilepsy: A Distinct Surgically Remediable Syndrome

Carne RP, O'Brien TJ, Kilpatrick CJ, MacGregor LR, Hicks RJ, Murphy MA, Bowden SC, Kaye AH, Cook MJ

Brain 2004;127:2276–2285

Most patients with nonlesional temporal lobe epilepsy (NLTLE) will have the findings of hippocampal sclerosis (HS) on a high-resolution MRI. However, a significant minority of patients with NLTLE and electroclinically well-lateralized temporal lobe seizures have no evidence of HS on MRI. Many of these patients have concordant hypometabolism on fluorodeoxyglucose-PET ([18F]FDG-PET). The pathophysiologic basis of this latter group remains uncertain. We aimed to determine whether NLTLE without HS on MRI represents a variant of or a different clinicopathologic syndrome from that of NLTLE with HS on MRI. The clinical, EEG, [18F]FDG-PET, histopathologic, and surgical outcomes of 30 consecutive NLTLE patients with well-lateralized EEG but without HS on MRI (HS–ve TLE) were compared with 30 consecutive age- and sex-matched NLTLE patients with well-lateralized EEG with HS on MRI (HS+ve TLE). Both the HS+ve TLE group and the HS–ve TLE patients had a high degree of [18F]FDG-PET concordant lateralization (26 of 30 HS–ve TLE vs. 27 of 27 HS+ve TLE). HS–ve TLE patients had more widespread hypometabolism on [18F]FDG-PET by blinded visual analysis [odds ratio (OR,+∞(2.51,–); P = 0.001]. The HS–ve TLE group less frequently had a history of febrile convulsions [OR,0.077 (0.002 to 0.512), P = 0.002], more commonly had a delta rhythm at ictal onset [OR,3.67 (0.97 to 20.47); P = 0.057], and less frequently had histopathologic evidence of HS [OR,0 (0 to 0.85); P = 0.031]. No significant difference in surgical outcome despite half of those without HS having a hippocampal-sparing procedure. Based on the findings outlined, HS–ve PET-positive TLE may be a surgically remediable syndrome distinct from HS+ve TLE, with a pathophysiologic basis that primarily involves lateral temporal neocortical rather than mesial temporal structures.
The Absence of Information about Hormones and Absence
Authors: Scharfman Helen E.
Published: May 2005

Hormonal Regulation of Absence Seizures

Persad V, Ting Wong CG, Cortez MA, Wang YT, Snead OC 3rd

Ann Neurol 2004;44:353–361

A time course study that examined the effects of the female estrous cycle on the chronic slow spike-and-wave discharges (SSWDs), GABAB-receptor (GABABR) binding, and GABABR protein expression was conducted in Long-Evans hooded rats treated during development with a cholesterol synthesis inhibitor AY9944 (AY). In addition, a pharmacologic study using the hormones progesterone, 17 β-estradiol, mifepristone (intracellular progesterone-receptor antagonist), tamoxifen (intracellular estrogen-receptor antagonist), and allopregnanolone (progesterone metabolite) was performed to determine their effects on AY-induced seizures. The data indicate that a significant increase occurs in both the duration of SSWDs and GABABR binding in the AY model during the proestrus stage of the estrous cycle, the stage during which the levels of progesterone are at their highest. No changes in GABABR1a or R2 protein levels were observed. In addition, the administration of both progesterone and allopregnanolone exacerbated seizures in the AY model, whereas 17 β-estradiol attenuated the SSWD duration. Neither mifepristone nor tamoxifen blocked the effects of progesterone and 17 β-estradiol, respectively, on SSWD duration in the AY model, suggesting that these two sex hormones are working in a manner independent of their intracellular receptors. These data suggest an important role for steroid hormones in the regulation and maintenance of AY-induced atypical absence seizures.
How to Explain Multidrug Resistance in Epilepsy?
Authors: Löscher Wolfgang
Published: May 2005

Despite advancements in antiepileptic therapy, about one third of people with epilepsy will remain intractable to medication. The initial response to antiepileptic drug therapy is highly predictive of long-term outcome. However, the mechanisms of medical intractability of epilepsy are only incompletely understood. Current interest is focused on two hypotheses: overexpression of drug efflux transporters and alterations in drug targets in the brain, with the most relevant causative mechanism(s) still to be elucidated.
Biatrial and Three‐Dimensional Mapping of Spontaneous Atrial Arrhythmias in Patients with Refractory Atrial Fibrillation
Authors: SAKSENA SANJEEV , SKADSBERG NICHOLAS D. , RAO HYGRIV B. , FILIPECKI ARTUR
Published: May 2005

Introduction: While atrial fibrillation (AF) initiation in the pulmonary veins has been well‐studied, simultaneous biatrial and three‐dimensional noncontact mapping (NCM) has not been performed. We hypothesized that these two techniques would provide novel information on triggers, initiation, and evolution of spontaneous AF and permit study of different AF populations.

Methods and Results: The origin of atrial premature beats (APBs), onset of spontaneous AF and its evolution were analyzed in 50 patients with AF in the presence or absence of structural heart disease (SHD) and in different AF presentations (group A: Persistent, group B: Paroxysmal). In 45 patients, spontaneous APBs in the right atrium (RA; n = 60) and left atrium (LA; n = 25) with similar regional distributions regardless of heart disease status were demonstrated. In total, 22 patients (44%) had ≥2 disparate regional origins. Biatrial regional foci were seen with equal frequency in patients with SHD (31%), without SHD (40%), in group A (32%), and in group B (36%). Biatrial mapping and NCM showed organized monomorphic atrial tachyarrhythmias arising in the RA (17), septum (17), or LA (21) and were classified as atrial flutter (RA = 34, LA = 8), macro‐reentrant atrial tachycardia (RA = 1, LA = 3) or focal atrial tachycardia (RA = 2, LA = 7). Their regional distribution was more extensive in patients with SHD and persistent AF compared with patients without SHD or paroxysmal AF. Simultaneous biatrial tachycardias were observed only in group A patients and those with SHD.

Conclusions: Simultaneous biatrial and NCM permits successful AF mapping in different AF populations and demonstrates a biatrial spectrum of spontaneous triggers and tachycardias. Organized monomorphic tachycardias with multiple unilateral or biatrial locations are commonly observed in human AF. Patients with heart disease or persistent AF have a more extensive distribution as well as simultaneous coexistence of multiple tachycardias during AF.
Catheter Ablation of Atrial Fibrillation Versus Atrioventricular Junction Ablation Plus Pacing Therapy for Elderly Patients with Medically Refractory Paroxysmal Atrial Fibrillation
Authors: HSIEH MING‐HSIUNG , TAI CHING‐TAI , LEE SHIH‐HUANG , TSAO HUAN‐MING , LIN YUNG‐KUO , HUANG JIN‐LONG , CHAN PAUL , CHEN YI‐JEN , KUO JEN‐YUAN , TUAN TA‐CHUAN , HSU TSUI‐LIEH , KONG CHI‐WOON , CHANG SHIH‐LIN , CHEN SHIH‐ANN
Published: May 2005

Background: Catheter ablation of atrial fibrillation (AF) has become another nonpharmacologic therapeutic option for medically refractory paroxysmal AF. Whether this method is better than atrioventricular (AV) junction ablation plus pacing therapy is unknown. The purpose of this study was to compare the very long‐term (longer than 4 years) clinical outcomes of the 2 methods in elderly patients (>65 years old) with medically refractory paroxysmal AF.

Methods: From January 1995 to December 2001, 71 elderly patients with medically refractory paroxysmal AF were included; group 1 included 32 patients with successful AV junction ablation plus pacing therapy and group 2, 37 patients with successful catheter ablation of AF.

Results: After a mean follow‐up of more than 52 months, the AF was better controlled in the group 1 patients than group 2 (100% vs 81%, P = 0.013), however, they had a significantly higher incidence of persistent AF (69% vs 8%, P < 0.001) and heart failure (53% vs 24%, P = 0.001). Furthermore, the incidence of ischemic stroke and cardiac death was similar between the 2 groups. Compared with the preablation values, a significant increase in the NYHA functional class (1.7 ± 0.9 vs 1.4 ± 0.7, P = 0.01) and significant decrease in the left ventricular ejection fraction (44 ± 8% vs 51 ± 10%, P = 0.01) were noted in the group 1 patients, but not in the group 2 patients.

Conclusions: Although AV junction ablation plus pacing therapy better controlled the AF in elderly patients with medically refractory paroxysmal AF, that method was associated with a higher incidence of persistent AF and heart failure than catheter ablation of AF in the very long‐term follow‐up.
The Antiarrhythmic Peptide Analog ZP123 Prevents Atrial Conduction Slowing During Metabolic Stress
Authors: HAUGAN KETIL , OLSEN KRISTINE BOISEN , HARTVIG LINE , PETERSEN JØRGEN SØBERG , HOLSTEIN‐RATHLOU NIELS‐HENRIK , HENNAN JAMES K. , NIELSEN MORTEN SCHAK
Published: May 2005

Objective: As atrial conduction slowing is important in the pathogenesis of atrial reentry arrhythmias, a drug that increases atrial conduction or prevents atrial conduction slowing could serve to prevent atrial reentry arrhythmias. In this study, we investigated whether the novel stable antiarrhythmic peptide analog, ZP123, was able to prevent atrial conduction slowing.

Methods: We examined the effect of ZP123 on metabolic stress‐induced changes in conduction velocity (CV) and on dynamic CV restitution in isolated left atria from male Sprague‐Dawley rats. We performed binding of ZP123 to a broad panel of 80 different cardiac and noncardiac ion channels and receptors and examined the effect of ZP123 on HERG channel conductance.

Results: ZP123 dose‐dependently prevented metabolic stress‐induced atrial CV slowing at doses ranging from 1 nM to 10 μM. ZP123 did not affect CV during physiological conditions nor did it affect dynamic CV restitution. ZP123 had no effect on atrial contractility. ZP123 showed no or low affinity binding to all ion channels and receptors examined. ZP123 had no effects on HERG channel activity in concentrations that affected atrial conduction. The concentration of ZP123 giving maximal effect on atrial conduction (100 nM) inhibited the outward K+‐current by 2.7 ± 0.1%.

Conclusion: ZP123 has no effects on atrial conduction during physiological conditions, but it selectively prevents atrial conduction slowing during metabolic stress.
Is Atrial Fibrillation a Genetic Disease?
Authors: BRUGADA RAMON
Published: May 2005

Atrial fibrillation remains one of the most challenging arrhythmias for the clinician and basic researcher. Different approaches have been undertaken to improve its understanding; from the development of animal models to the analysis of genetic backgrounds in individuals with familial and acquired forms of the disease. In the last few years, a large body of evidence has shown that alterations in ionic currents are involved in the disease. However, it has not been until recently, with the genetic link between mutations in proteins responsible for these ionic currents and the familial disease, that we have been given the final evidence that atrial fibrillation can also be primarily an ion channelopathy. Despite the limited prevalence of the inherited diseases, it has been shown before that the knowledge gained in their study will be helpful in dealing with the most common acquired forms of the disease. Therefore, as data keep unraveling, clinicians can expect that soon better therapeutic and preventive options for atrial fibrillation will emerge from basic science.
A Novel Missense Mutation in the SCN5A Gene Associated with Brugada Syndrome Bidirectionally Affecting Blocking Actions of Antiarrhythmic Drugs
Authors: ITOH HIDEKI , SHIMIZU MASAMI , TAKATA SHIGEO , MABUCHI HIROSHI , IMOTO KEIJI
Published: May 2005

Brugada syndrome is an inherited cardiac disorder caused by mutations in the SCN5A gene encoding the cardiac sodium channel α subunit, which can lead ventricular fibrillation and sudden death. Inattentive use of antiarrhythmic drugs potentially triggers fatal cardiac arrhythmias through further reduction of sodium current (INa). We studied the molecular mechanism underlying a case of Brugada syndrome that showed no response to a class Ic antiarrhythmic drug. Molecular genetic studies of a patient with Brugada syndrome identified a novel mutation in SCN5A, which causes substitution of serine for asparagine (N406S) in S6 of domain I (IS6). The provocation test with pilsicainide, a class Ic antiarrhythmic drug, failed to exacerbate ST‐segment elevation in this case. Electrophysiological analyses of the N406S‐mutant channel expressed together with the β1 subunit in HEK293 cells showed that the voltage dependence of activation was positively shifted by 16 mV and that intermediate inactivation was enhanced. Whereas tonic block by pilsicainide was not changed in the N406S channel, use‐dependent block by pilsicainide was almost completely abolished, consistent with the clinical findings of the negative provocation test. In contrast, the N406S channel showed stronger use‐dependent block by quinidine than the wild‐type channel. We demonstrate a novel Brugada mutation N406S, which is associated with the discordant effects on blocking actions of antiarrhythmic drugs as well as the multiple channel gating defects. We emphasis that an antiarrhythmic drug may exert unpredicted effects in patients with channel mutations.
The role of dopamine in reward and pleasure behaviour – review of data from preclinical research
Authors: Bressan R. A. , Crippa J. A.
Published: May 2005

Objective:  The purpose of this article is to review some of the basic aspects of the dopaminergic system and its role in reward and pleasure behaviour. We also discuss the association between dopamine and unpleasant symptoms that are commonly found in neuropsychiatric disorders and may also be side‐effects of neuroleptic drugs.

Method:  A computer‐based search of the literature, augmented by extensive bibliography‐guided article reviews, were used to find basic information on the dopamine and the reward systems, and symptoms such as dysphoria, anhedonia and depression.

Results:  Central dopaminergic neurotransmission is complex, having multiple actions at each level of the mesocorticolimbic reward pathway. The role of dopamine in the reward process was classically associated with the ability to experience pleasure; recent data suggest a more motivational role. Dysfunction of the dopamine transmission in the reward circuit is associated with symptoms such as anhedonia, apathy and dysphoria found in several neuropsychiatric disorders, including Parkinson's disease, depression, drug addiction, and neuroleptic‐induced dysphoria.

Conclusion:  Viewing the dysfunctions of the reward pathways within a broader spectrum and exploring its complex relations with the dopaminergic transmission may help understand the pathophysiology of these neuropsychiatric disorders and lead to a rational development of novel treatments.
Brain imaging research on subjective responses to psychotropic drugs
Authors: Voruganti L. P. , Awad A. G.
Published: May 2005

Objective:  Neuroimaging studies on subjective responses to psychotropic drugs in humans were reviewed to examine progress in the field and identify gaps in knowledge.

Method:  An exhaustive search of computerized databases identified two categories of in vivo imaging studies: i) correlates of negative (dysphoric) subjective responses to neuroleptic use in schizophrenia, and ii) research on positive (euphoric) subjective responses, mostly from substance abuse population.

Results:  Research has been largely confined to neurochemical imaging of dopamine in the striatal complex, confirming earlier speculations that impaired or deficient dopaminergic function is associated with dysphoric responses, and enhanced activity is associated with euphoric or pleasurable responses. Cerebral blood flow, regional metabolic rate and glucose utilization studies provided preliminary clues to the putative neuroanatomical sites.

Conclusion:  Neuroimaging techniques added credibility to the study of subjective responses; however, further studies are required to identify the underlying anatomical and neurochemical interactions in order to enhance their applied value.
Adolescence, schizophrenia and drug abuse: a window of vulnerability
Authors: van Nimwegen L. , de Haan L. , van Beveren N. , van den Brink W. , Linszen D.
Published: May 2005

Objective:  To discuss the neurobiological and psychosocial developmental factors in adolescence contributing to simultaneous onset and co‐occurrence of psychosis and substance use disorders.

Method:  A review of the literature.

Results:  Adolescence is a period with specific psychosocial challenges and specific changes in the brain that increase the probability of the onset of both psychosis and substance abuse, in predisposed people. In vulnerable adolescents it is proposed that an excessive pruning of dopaminergic neurones leads to mesocortical hypofrontality causing anhedonia and dysphoria. At the same time, anhedonia and dysphoria are important risk factors for the development of substance abuse. In turn, hypofrontality leads to a reduction in mesocortical feedback inhibition of the mesolimbic system resulting in aberrant salience and positive symptoms. Finally, the development of aberrant salience plays a role in both psychoses and craving.

Conclusion:  Attention should be paid to the interaction of drug abuse and schizophrenia and an integrated treatment is needed. Dysphoria and anhedonia in schizophrenic adolescents are important factors in treatment with antipsychotic medication, both in terms of patient satisfaction and in the prevention of substance abuse.
Subjective experiences on antipsychotic medications: synthesis and conclusions
Authors: Marder S. R.
Published: May 2005

Objective:  This report synthesizes the literature describing the phenomenology, clinical importance and biology of subjective responses to antipsychotic medications in schizophrenia. A patient's experience of an antipsychotic is important because unpleasant or dysphoric responses can impair therapeutic relationships, lead to medication non‐adherence, and have direct negative effects on a patient's quality of life.

Method:  The author selectively reviewed early studies of subjective responses to antipsychotics and integrated this literature with the work of the other investigators in this special section.

Results:  There is substantial evidence that second‐generation antipsychotics have advantages in causing fewer dysphoric responses when compared with first‐generation agents. Clinical and neuroimaging studies suggest that dopamine blockade is an important determinant of many of these dysphorias. At this point in time it is unclear whether dysphoria results from extrapyramidal symptoms – particularly akathisia and akinesia – or whether they are a direct result of decreased dopamine activity.

Conclusion:  Clinicians and researchers should continue to monitor dysphorias in schizophrenia. Contributions by the authors in this supplement provide new and more refined methods for measuring subjective responses in future studies.
Effective in vivo purging with rituximab and autologous peripheral blood stem cell transplantation in a woman with CD5 positive primary cutaneous diffuse large B‐cell lymphoma
Authors: Goto H. , Nishio M. , Endo T. , Sato N. , Koizumi K. , Fujimoto K. , Sakai T. , Kumano K. , Obara M. , Koike T.
Published: May 2005

Abstract:  Generalized subcutaneous tumors developed without any other sites of the disease in a Japanese woman. Skin biopsy revealed CD5+ and CD20+ atypical diffuse large cells infiltrating subcutaneous tissues. The diagnosis was CD5+ primary cutaneous diffuse large B‐cell lymphoma. Tumor‐specific PCR showed the existence of malignant cells in the peripheral blood and bone marrow. After three cycles of chemotherapy, she was remained in partial remission. Peripheral blood stem cells (PBSC) were harvested after the fourth cycles of chemotherapy combined with rituximab for in vivo purging. The contamination of tumor cells in PBSC was negative with PCR. She then underwent autologous peripheral blood stem cell transplantation using purged PBSC and has remained in complete remission for the past 24 month.
The bisphosphonate zoledronic acid inhibits the development of plasmacytoma induced in BALB/c mice by intraperitoneal injection of pristane
Authors: Avcu Ferit , Ural Ali Ugur , Yilmaz Mahmut Ilker , Ozcan Ayhan , Ide Tayfun , Kurt Bulent , Yalcin Atilla
Published: May 2005

Abstract:  Objectives: Bisphosphonates (BPs) are mostly used in the palliative care of myeloma‐associated osteolytic lesions. Recent studies have suggested that BPs may also exert direct antitumor effects on myeloma cells. We have investigated the effect of the potent bisphosphonate, zoledronic acid (ZOL), on the development of pristane (2,6,10,14‐tetramethylpentadecane)‐induced plasmacytoma (PCT) in six‐week‐old BALB/c mice. Methods: Different groups of pristane‐treated mice also received ZOL (100 μg/kg) commencing after the development of PCT or ZOL (20 μg/kg) from the first day. Control groups received pristane alone, ZOL alone (20 μg/kg), or phosphate‐buffered saline. The study was terminated on day 300, and the remaining mice were autopsied and abdominal tissues were examined histologically for PCT. Results and conclusions: Statistical analysis revealed a significant delay in PCT development in the group receiving pristane plus ZOL (20 μg/kg) from the first day compared to the groups receiving pristane alone and pristane combined with ZOL (100 μg/kg) after the appearance of PCT (Log‐rank, P = 0.0001 and 0.0001; respectively). Kaplan–Meier analysis revealed a significant difference in survival between the group treated with pristane alone and the groups receiving pristane plus ZOL (20 μg/kg) from the first day or ZOL (100 μg/kg) after the appearance of PCT (Log‐rank, P = 0.016 and 0.023; respectively). These results indicate a direct anti‐tumor effect of ZOL in pristane‐induced PCT development BALB/c mice, which may contribute to their significantly increased survival. This hypothesis should now be further investigated in clinical trials.
Successful non‐T‐cell‐depleted HLA‐haploidentical 3‐loci mismatched bone marrow transplantation
Authors: Yagyu Shigeki , Kuroda Hiroshi , Fujiki Atsushi , Tamura Shinichi , Iehara Tomoko , Morimoto Akira , Hosoi Hajime , Sugimoto Tohru , Imashuku Shinsaku
Published: May 2005

Abstract:  A 17‐year‐old boy with therapy‐related acute myelocytic leukemia (FAB classification‐M0) successfully received allogeneic non‐T‐cell depleted (non‐TCD) bone marrow transplantation (BMT) from his 3‐loci HLA‐mismatch mother, although pre‐BMT detection of feto‐maternal microchimerism was negative. The BMT was performed with reduced intensity conditioning (total body irradiation; 4 Gy, fludarabine; 20 mg/m2 × 6, and melphalan; 70 mg/m2 × 2) and short‐course methotrexate and tacrolimus for GVHD prophylaxis. Complete donor chimera was obtained on day 19, associated with Grade 3 acute GVHD (skin: Stage 1, liver: Stage 0, gut: Stage 3) that was well controlled with immunosuppressive therapies. At day 200 of transplantation, he was in complete remission with no signs of chronic GVHD. Our case suggests that non‐TCD HLA‐haploidentical 3‐loci mismatched BMT can be safely performed from mother to offspring even when feto‐maternal microchimerism is barely detectable with the current detection procedure.
Early detection of cardiac dysfunction in thalassemic patients by radionuclide angiography and heart rate variability analysis
Authors: Chiara Benedetta De , Crivellaro Wilma , Sara Roberto , Ruffini Livia , Parolini Marina , Fesslovà Vlasta , Carnelli Vittorio , Fiorentini Cesare , Parodi Oberdan
Published: May 2005

Abstract:  Background: Cardiac dysfunction remains the major cause of death in beta‐thalassemia. Aim of this study was to assess early myocardial damage in thalassemic patients with no symptoms or echocardiographic evidence of dysfunction at routine monitoring. Methods: Twenty patients (seven females; median 25 yr [first quartile 22,third quartile 28]) with beta‐thalassemia underwent radionuclide angiography (RNA) at rest and during low‐dose dobutamine infusion (5–10 γ/kg/min). Right and left ventricular ejection fractions (EF) were determined by first‐pass method and gated equilibrium acquisition, respectively. Twenty‐four‐hour Holter monitoring with time‐domain heart rate variability (HRV) assessment and echocardiographic follow‐up (21 months [5,27]) were performed. Results: Eleven patients showed regional wall motion abnormalities at RNA; left ventricular EF, HR and diastolic measurements significantly increased after dobutamine infusion. Patients with abnormal RNA right ventricular EF (n = 8, <0.45) showed lower echocardiographic left ventricular EF at the enrolment (0.54 [0.50,0.61] vs. 0.62 [0.56,0.67], P = 0.02) than those with a normal right ventricular EF. Patients with reduced standard deviation of the averages of RR intervals in all 5‐minute periods of entire recording (SDANN) (n = 6, <100 ms), a measure of HRV, had lower echocardiographic left ventricular EF (0.53 [0.49,0.62] vs. 0.62 [0.56,0.66], P = 0.03) and lower fractional shortening (0.28 [0.25,0.32] vs. 0.36 [0.30,0.39], P = 0.003) at the enrolment than those with normal SDANN. No significant association was found between RNA and HRV measurements and follow‐up left ventricular function. Conclusions: Right ventricular dysfunction and abnormal HRV may represent the early features of cardiac disease in thalassemic patients with no evidence of ventricular dysfunction at routine evaluation.
Psychoanalyse und Peter Weiss’ Experimentalfilme1
Authors: Knittel Von Anton Philipp
Published: May 2005

Texte von Peter Weiss psychoanalytisch zu deuten, hat die Literaturwissenschaft mehrfach unternommen; etwas abseits standen bislang meist seine Filme. Diese greifen in erster Linie auf synkretistische Traumtheoreme der Surrealisten zurück; Buñuel und Dalí waren die großen Vorbilder des Filmemachers Peter Weiss. In seinen Experimentalfilmen werden mittels filmischer Techniken – wie beispielsweise iterative Schnitte, ungewöhnliche Kameratechniken und Perspektiven – sowie durch wiederholte Fragmentierungen des menschlichen Körpers und die Dekomposition von sinnstiftenden Handlungseinheiten die für sein gesamtes künstlerisches Schaffen zentralen Themen von Isolation und (Selbst‐)Befreiung medial inszeniert. Sichtbar wird jedoch zugleich auch die Grenze kinematografischen Nachvollzugs einer autopoietischen Selbstkonstitution mit dem Ziel einer Befreiung zur Kunst.
Reframing Research on Sexual Behavior and HIV
Authors: Obermeyer Carla Makhlouf
Published: May 2005

This review of recent studies examines the conceptual and methodological tools that are used to understand sexual behavior and HIV. Whereas surveys have provided reliable indicators of behavior, their validity is uncertain, their correlation with biological indicators tenuous, and the explanations they offer limited. Microlevel research has called into question the rationalizing, medically informed, and risk‐averse frameworks used in the public health literature on HIV and behavior, but its impact has been limited. Thus, surveys and qualitative research have proceeded along two separate tracks, and this separation has hampered our understanding of sexual behavior. A small but growing number of studies, however, provide examples of less‐compartmentalized research that avoids oversimplification. They show that expanding the models that drive research in this area is possible, and that efforts to combine disciplinary perspectives result in deeper understandings of knowledge, risk perceptions, attitudes, and behavioral change.
Hormonal Contraception and Physiology: A Research‐based Theory of Discontinuation Due to Side Effects
Authors: Vitzthum Virginia J. , Ringheim Karin
Published: May 2005

Side effects influence the acceptability and continuation of hormonal contraceptives. Counseling the client about the management of side effects is a principal approach advocated for increasing continuation. Evidence of a biological basis for variation in women's tolerance of hormonal contraceptives argues, however, that greater attention should be given to altering the product rather than principally attempting to alter a woman's ability to deal with the product. Discontinuation rates for hormonal contraceptives, largely attributable to side effects and health concerns, are high in nearly all less‐developed countries for which Demographic and Health Survey data are available. Oral contraceptives appear to be particularly problematic for Latin American women, most notably in Bolivia. Clinical trials suggest substantial variation in the physiological response to exogenous hormones, and new evidence confirms the hypothesis that the normal hormonal profiles of Bolivian women are significantly lower than those of women in the United States. These findings suggest a need for more population‐specific physiological research linked to analyses of the possible association between endogenous hormone differences and contraceptive continuation. Appropriately adjusting the level of the steroid delivered may benefit women's health and improve the acceptability and continuation of hormonal contraceptives.
The Impact of Franchised Family Planning Clinics in Poor Urban Areas of Pakistan
Authors: Hennink Monique , Clements Steve
Published: May 2005

This study uses a quasi‐experimental design to determine the impact of new family planning clinics on knowledge, contraceptive use, and unmet need for family planning among married women in poor urban areas of six secondary cities of Pakistan. Baseline (n = 5,338) and end line (n = 5,502) population surveys were conducted during 1999–2000 and 2001–02 in four study sites and two control sites. Exit interviews with clients identified the socio demographic and geographic characteristics of clinic users. The results show that the clinics contributed to a 5 percent increase in overall knowledge of family planning methods and an increase in knowledge of female sterilization and the IUD of 15 percent and 7 percent, respectively. Distinct effects were found on contraceptive uptake, including an 8 percent increase in female sterilization and a 7 percent decline in condom use. Unmet need for family planning declined in two sites, whereas impacts on the other sites were variable. Although the new clinics are located within poor urban communities, users of the services were not the urban poor, but rather were select subgroups of the local population.
Factors Influencing Boys' Age at First Intercourse and Condom Use in the Shantytowns of Recife, Brazil
Authors: Juarez Fatima , LeGrand Thomas
Published: May 2005

Despite the general recognition that the sexual practices of adolescent boys place them at high risk of acquiring sexually transmitted infections (STIs), including HIV, and of causing unwanted pregnancies, advances in mapping their sexual behaviors have been slow. This study uses data recently collected from low‐income areas of the city of Recife, Brazil, to study boys' age at first sexual intercourse and factors that hinder their use of condoms. These boys become sexually active at early ages, and despite their general awareness of HIV, they rarely use condoms, especially at ages younger than 15. Sustained family involvement in guiding boys is associated with later first intercourse and an increased use of condoms. Boys who describe themselves as shy with girls have later first intercourse, although the probability of their using condoms does not differ from that of other boys of their age. Higher socioeconomic status leads to earlier sexual activity for boys (in contrast with girls), but also to a greater likelihood of using condoms during first intercourse.
Reproductive Health and the Millennium Development Goals: The Missing Link
Authors: Crossette Barbara
Published: May 2005

This report was commissioned by the Population Program of the William and Flora Hewlett Foundation in December 2004. The author was charged with analyzing the United Nations' deliberations that led to the adoption of the Millennium Development Goals (MDGs) to answer the question of why there is no specific reproductive health goal. Her report, of which this is a lightly edited version, is also available online at 〈;http://www.hewlett.org/programs/population/publications.crossettereport.htm〉.

This coverage of the MDG process will be complemented by a special section of Studies in the June 2005 issue on reproductive health and the MDGs. The section will include excerpts about reproductive health from the final report of the Millennium Development Project entitled “Investing in Development: A Practical Plan to Achieve the Millennium Development Goals,” which was submitted to Secretary General Kofi Annan in January 2005, as well as commentaries by leading scholars and policymakers in the fields of population and reproductive health.
Analytical representation for Varian EDW factors at off‐center points
Authors: Kuperman Vadim Y.
Published: May 2005

The purpose of this study is to describe and evaluate a new analytical model for Varian enhanced dynamic wedge factors at off‐center points. The new model was verified by comparing measured and calculated wedge factors for the standard set of wedge angles (i.e., 15°, 30°, 45° and 60°), different symmetric and asymmetric fields, and two different photon energies. The maximum difference between calculated and measured wedge factors is less than 2%. The average absolute difference is within 1%. The obtained results indicate that the suggested model can be useful for independent dose calculation with enhanced dynamic wedges.