bluuebunny/crossref_metadata_2025 huggingface dataset:
The Convolution on Time Scales
Authors: Bohner Martin , Guseinov Gusein Sh.
Published: July 2007

The main theme in this paper is an initial value problem containing a dynamic version of the transport equation. Via this problem, the delay (or shift) of a function defined on a time scale is introduced, and the delay in turn is used to introduce the convolution of two functions defined on the time scale. In this paper, we give some elementary properties of the delay and of the convolution and we also prove the convolution theorem. Our investigation contains a study of the initial value problem under consideration as well as some results about power series on time scales. As an extensive example, we consider theq-difference equations case.
The Role of PPARs in Lung Fibrosis
Authors: Lakatos Heather F. , Thatcher Thomas H. , Kottmann R. Matthew , Garcia Tatiana M. , Phipps Richard P. , Sime Patricia J.
Published: July 2007

Pulmonary fibrosis is a group of disorders characterized by accumulation of scar tissue in the lung interstitium, resulting in loss of alveolar function, destruction of normal lung architecture, and respiratory distress. Some types of fibrosis respond to corticosteroids, but for many there are no effective treatments. Prognosis varies but can be poor. For example, patients with idiopathic pulmonary fibrosis (IPF) have a median survival of only 2.9 years. Prognosis may be better in patients with some other types of pulmonary fibrosis, and there is variability in survival even among individuals with biopsy-proven IPF. Evidence is accumulating that the peroxisome proliferator-activated receptors (PPARs) play important roles in regulating processes related to fibrogenesis, including cellular differentiation, inflammation, and wound healing. PPARαagonists, including the hypolidipemic fibrate drugs, inhibit the production of collagen by hepatic stellate cells and inhibit liver, kidney, and cardiac fibrosis in animal models. In the mouse model of lung fibrosis induced by bleomycin, a PPARαagonist significantly inhibited the fibrotic response, while PPARαknockout mice developed more serious fibrosis. PPARβ/δappears to play a critical role in regulating the transition from inflammation to wound healing. PPARβ/δagonists inhibit lung fibroblast proliferation and enhance the antifibrotic properties of PPARγagonists. PPARγligands oppose the profibrotic effect of TGF-β, which induces differentiation of fibroblasts to myofibroblasts, a critical effector cell in fibrosis. PPARγligands, including the thiazolidinedione class of antidiabetic drugs, effectively inhibit lung fibrosis in vitro and in animal models. The clinical availability of potent and selective PPARαand PPARγagonists should facilitate rapid development of successful treatment strategies based on current and ongoing research.
On Certain Multivalent Functions
Authors: Nunokawa Mamoru , Owa Shigeyoshi , Sekine Tadayuki , Yamakawa Rikuo , Saitoh Hitoshi , Nishiwaki Junichi
Published: July 2007

Let𝒮*(p,α)be the class of functionsf(z)which are analytic andp-valently starlike of orderαin the open unit diskE. The object of the present paper is to derive an interesting condition forf(z)to be in the class𝒮*(p,α).
Remarks on Separation of Convex Sets, Fixed-Point Theorem, and Applications in Theory of Linear Operators
Authors: Soltanov Kamal N
Published: July 2007

Some properties of the linear continuous operator and separation of convex subsets are investigated in this paper and a dual space for a subspace of a reflexive Banach space with a strictly convex norm is constructed. Here also an existence theorem and fixed-point theorem for general mappings are obtained. Moreover, certain remarks on the problem of existence of invariant subspaces of a linear continuous operator are given.
Quality-Based Backlight Optimization for Video Playback on Handheld Devices
Authors: Cheng Liang , Mohapatra Shivajit , El Zarki Magda , Dutt Nikil , Venkatasubramanian Nalini
Published: July 2007

For a typical handheld device, the backlight accounts for a significant percentage of the total energy consumption (e.g., around 30% for a Compaq iPAQ 3650). Substantial energy savings can be achieved by dynamically adapting backlight intensity levels on such low-power portable devices. In this paper, we analyze the characteristics of video streaming services and propose a cross-layer optimization scheme called quality adapted backlight scaling (QABS) to achieve backlight energy savings for video playback applications on handheld devices. Specifically, we present a fast algorithm to optimize backlight dimming while keeping the degradation in image quality to a minimum so that the overall service quality is close to a specified threshold. Additionally, we propose two effective techniques to prevent frequent backlight switching, which negatively affects user perception of video. Our initial experimental results indicate that the energy used for backlight is significantly reduced, while the desired quality is satisfied. The proposed algorithms can be realized in real time.
Variation-Tolerant and Low-Power Source-Synchronous Multicycle On-Chip Interconnect Scheme
Authors: Ghoneima Maged , Ismail Yehea , Khellah Muhammad , De Vivek
Published: July 2007

A variation-tolerant low-power source-synchronous multicycle (SSMC ) interconnect
scheme is proposed. This scheme is scalable and suitable for transferring data across
different clock domains such as those in “many-core” SoCs and in
3D-ICs. SSMC replaces intermediate flip-flops by a source-synchronous synchronization
scheme. Removing the intermediate flip-flops in the SSMC scheme enables better averaging
of delay variations across the whole interconnect, which reduces bit-rate degradation due to
within-die WID process variations. Monte Carlo circuit simulations show that SSMC eliminates
90% of the variation-induced performance degradation in a 6-cycle 9 mm-long
16-bit conventional bus.
The proposed multicycle bus scheme also leads to significant energy savings due to eliminating
the power-hungry flip-flops and efficiently designing the source synchronization
overhead. Moreover, eliminating intermediate flip-flops avoids the timing overhead of the setup
time, the flip-flop delay, and the single-cycle clock jitter. This delay slack can then be translated into
further energy savings by downsizing the repeaters. The significant delay jitter due to capacitive
coupling has been addressed and solutions are put forward to alleviate it. Circuit simulations in
a  65-nm process environment indicate that energy savings up to 20% are achievable for a 6-cycle 9 mm long 16-bit bus.
Trastuzumab causes antibody-dependent cellular cytotoxicity–mediated growth inhibition of submacroscopic JIMT-1 breast cancer xenografts despite intrinsic drug resistance
Authors: Barok Márk , Isola Jorma , Pályi-Krekk Zsuzsanna , Nagy Péter , Juhász István , Vereb György , Kauraniemi Päivikki , Kapanen Anita , Tanner Minna , Vereb György , Szöllösi János
Published: July 2007

Trastuzumab is a recombinant antibody drug that is widely used for the treatment of breast cancer. Despite encouraging clinical results, some cancers are primarily resistant to trastuzumab, and a majority of those initially responding become resistant during prolonged treatment. The mechanisms of trastuzumab resistance have not been fully understood. We examined the role of antibody-dependent cellular cytotoxicity (ADCC) using JIMT-1 cells that are ErbB2 positive but intrinsically resistant to trastuzumab in vitro. Unexpectedly, in experiments mimicking adjuvant therapy of submacroscopic disease in vivo (JIMT-1 cells inoculated s.c. in severe combined immunodeficiency mice), trastuzumab was able to inhibit the outgrowth of macroscopically detectable xenograft tumors for up to 5–7 weeks. The effect is likely to be mediated via ADCC because trastuzumab-F(ab′)2 was ineffective in this model. Moreover, in vitro ADCC reaction of human leukocytes was equally strong against breast cancer cells intrinsically sensitive (SKBR-3) or resistant (JIMT-1) to trastuzumab or even against a subline of JIMT-1 that was established from xenograft tumors growing despite trastuzumab treatment. These results suggest that ADCC may be the predominant mechanism of trastuzumab action on submacroscopic tumor spread. Thus, measuring the ADCC activity of patient's leukocytes against the tumor cells may be a relevant predictor of clinical trastuzumab responsiveness in vivo. [Mol Cancer Ther 2007;6(7):2065–72]
Intratumoral expression of respiratory syncytial virus fusion protein in combination with cytokines encoded by adenoviral vectors asin situtumor vaccine for colorectal cancer
Authors: Hoffmann Dennis , Bayer Wibke , Grunwald Thomas , Wildner Oliver
Published: July 2007

Although cancers can naturally elicit immune responses, immune ignorance is a common observation preventing immune-mediated elimination of tumor cells. We assessed whether intratumoral expression of respiratory syncytial virus fusion (RSV-F) protein, encoded by a replication-defective adenovirus vector (Ad.RSV-F), alone or in combination with local coexpression of cytokines can induce tumor-specific immune responses in a syngeneic murine colon cancer model. We confirmed in vitro by dye colocalization that transduction of murine cells with Ad.RSV-F induces cell-cell fusion. In vivo, we showed in a bilateral syngeneic s.c. colon cancer model in C57BL/6 and BALB/c mice that intratumoral injection of Ad.RSV-F leads to a significant volume reduction not only of the directly vector-treated tumor but also of the contralateral not directly vector-treated tumor. The intratumoral administration of Ad.RSV-F in combination with adenovirus vectors encoding interleukin (IL)-2, IL-12, IL-18, IL-21, or granulocyte macrophage colony-stimulating factor significantly enhanced the antitumor effect on the directly vector-treated tumor and also on the contralateral tumor. The antineoplastic efficacy of this combined treatment was significantly higher than that of the individual treatment components and was associated with the induction of a tumor-specific CTL response and increased infiltration of the tumors by natural killer cells and macrophages. Intratumoral coexpression of RSV-F and IL-21 resulted in the highest tumor growth inhibition and improved survival. Our experimental data indicate that intratumoral expression of RSV-F in combination with cytokines is a promising novel tool for the development of in situ tumor vaccination approaches. [Mol Cancer Ther 2007;6(7):1942–50]
Potentiation of antileukemic therapies by Smac mimetic, LBW242: effects on mutant FLT3-expressing cells
Authors: Weisberg Ellen , Kung Andrew L. , Wright Renee D. , Moreno Daisy , Catley Laurie , Ray Arghya , Zawel Leigh , Tran Mary , Cools Jan , Gilliland Gary , Mitsiades Constantine , McMillin Douglas W. , Jiang Jingrui , Hall-Meyers Elizabeth , Griffin James D.
Published: July 2007

Members of the inhibitor of apoptosis protein (IAP) family play a role in mediating apoptosis. Studies suggest that these proteins may be a viable target in leukemia because they have been found to be variably expressed in acute leukemias and are associated with chemosensitivity, chemoresistance, disease progression, remission, and patient survival. Another promising therapeutic target, FLT3, is mutated in about one third of acute myelogenous leukemia (AML) patients; promising results have recently been achieved in clinical trials investigating the effects of the protein tyrosine kinase inhibitor PKC412 on AML patients harboring mutations in the FLT3 protein. Of growing concern, however, is the development of drug resistance resulting from the emergence of point mutations in targeted tyrosine kinases used for treatment of acute leukemia patients. One approach to overriding resistance is to combine structurally unrelated inhibitors and/or inhibitors of different signaling pathways. The proapoptotic IAP inhibitor, LBW242, was shown in proliferation studies done in vitro to enhance the killing of PKC412-sensitive and PKC412-resistant cell lines expressing mutant FLT3 when combined with either PKC412 or standard cytotoxic agents (doxorubicin and Ara-c). In addition, in an in vivo imaging assay using bioluminescence as a measure of tumor burden, a total of 12 male NCr-nude mice were treated for 10 days with p.o. administration of vehicle, LBW242 (50 mg/kg/day), PKC412 (40 mg/kg/day), or a combination of LBW242 and PKC412; the lowest tumor burden was observed in the drug combination group. Finally, the combination of LBW242 and PKC412 was sufficient to override stromal-mediated viability signaling conferring resistance to PKC412. [Mol Cancer Ther 2007;6(7):1951–61]
Lessons learned in the development of targeted therapy for malignant gliomas
Authors: Omuro Antonio M.P. , Faivre Sandrine , Raymond Eric
Published: July 2007

The prognosis of patients with glioblastoma, anaplastic astrocytoma, and anaplastic oligodendroglioma remains poor despite standard treatment with radiotherapy and temozolomide. Molecular targeted therapy holds the promise of providing new, more effective treatment options with minimal toxicity. However, the development of targeted therapy for gliomas has been particularly challenging. The oncogenetic process in such tumors is driven by several signaling pathways that are differentially activated or silenced with both parallel and converging complex interactions. Therefore, it has been difficult to identify prevalent targets that act as key promoters of oncogenesis and that can be successfully addressed by novel agents. Several drugs have been tested, including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (gefitinib and erlotinib), mammalian target of rapamycin (mTOR) inhibitors (temsirolimus and everolimus), and vascular endothelial growth factor receptor (VEGFR), protein kinase C-β, and other angiogenesis pathways inhibitors (vatalanib, bevacizumab, and enzastaurin). Although preliminary efficacy results of most trials in recurrent disease have fallen short on expectations, substantial advances have been achieved by associated translational research. In this article, we seek to recapitulate the lessons learned in the development of targeted therapy for gliomas, including challenges and pitfalls in the interpretation of preclinical data, specific issues in glioma trial design, insights provided by translational research, changes in paradigms, and future perspectives. [Mol Cancer Ther 2007;6(7):1909–19]
Sensitizing HER2-overexpressing cancer cells to luteolin-induced apoptosis through suppressing p21WAF1/CIP1 expression with rapamycin
Authors: Chiang Chun-Te , Way Tzong-Der , Lin Jen-Kun
Published: July 2007

HER2 overexpression, which confers resistance to various therapeutic regimens, correlates with a poor clinical prognosis. In this study, we showed that luteolin, a naturally occurring flavonoid, is a potent stimulator of HER2 degradation. Luteolin effectively inhibited cell proliferation and induced apoptosis in HER2-overexpressing cancer cells. Furthermore, we found that low doses of luteolin up-regulated p21 expression and high doses of luteolin down-regulated its expression. Examination of the Akt/mammalian target of rapamycin (mTOR) signaling revealed that this signaling was only transiently inhibited by low doses of luteolin, which suggested that the inability to cause sustained Akt/mTOR inhibition may contribute to p21 induction and provide a survival advantage to HER2-overexpressing cancer cells. To test this hypothesis, we showed that the combined use of luteolin and mTOR inhibitor rapamycin prevented low doses of luteolin from inducing p21 expression, and HER2-overexpressing cancer cells would be sensitized toward luteolin-induced apoptosis. In addition, p21 small interfering RNA also increased the luteolin-induced cell death. In nude mice with xenografted SKOV3.ip1-induced tumors, luteolin significantly inhibited HER2 expression and tumor growth in a dose-dependent manner, and rapamycin further enhanced the effect of luteolin with a concomitant p21 inhibition. These results reveal an intriguing finding that suppressing p21 expression might have therapeutic implications and further suggest that combination of mTOR inhibitors may be a promising strategy to help increase the efficacy of preventive or therapeutic compounds against HER2-overexpressing tumors. [Mol Cancer Ther 2007;6(7):2127–38]
Ovarian cancer cell–derived migration inhibitory factor enhances tumor growth, progression, and angiogenesis
Authors: Hagemann Thorsten , Robinson Stephen C. , Thompson Richard G. , Charles Kellie , Kulbe Hagen , Balkwill Frances R.
Published: July 2007

In view of our previous findings that tumor cell–derived macrophage migration inhibitory factor (MIF) increased macrophage-mediated ovarian cancer cell invasiveness in vitro, we investigated the wider significance of ovarian cancer cell–derived MIF for tumor growth, metastasis, and angiogenesis. We found that MIF is expressed in borderline and malignant ovarian tumors, and active MIF is found in malignant ascitic fluid. We next investigated the expression and function of MIF in a syngeneic ovarian cancer model. Stable knockdown of MIF in the murine ovarian cancer cell line ID8 decreased in vivo tumor burden and overall survival. Tumors arising from MIF knockdown cells had decreased proliferation and significantly increased apoptosis. This was associated with an increased phosphorylation of p53 and reduced Akt phosphorylation. MIF knockdown led to a changed cytokine profile in the ascitic microenvironment; tumor necrosis factor-α, interleukin-6 (IL-6), and IL-10 expression were all significantly decreased. Accompanying this decrease in cytokine expression was a significant decrease in macrophage infiltration into ascites. Additionally, MIF knockdown reduced the expression of proangiogenic cytokines vascular endothelial growth factor and keratinocyte chemoattractant (KC) and reduced the amount of endothelial cells in the malignant ascites. We conclude that autocrine production of MIF by ovarian cancer cells stimulates other cytokines, chemokines, and angiogenic factors that may promote colonization of the peritoneum and neovascularization of tumor deposits. [Mol Cancer Ther 2007;6(7):1993–2002]
Inhibition of the mitogen-activated protein kinase pathway results in the down-regulation of P-glycoprotein
Authors: Katayama Kazuhiro , Yoshioka Sho , Tsukahara Satomi , Mitsuhashi Junko , Sugimoto Yoshikazu
Published: July 2007

The multidrug resistance gene 1 (MDR1) product, P-glycoprotein (P-gp), pumps out a variety of anticancer agents from the cell, including anthracyclines, Vinca alkaloids, and taxanes. The expression of P-gp therefore confers resistance to these anticancer agents. In our present study, we found that FTI-277 (a farnesyltransferase inhibitor), U0126 [an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)], and 17-allylamino-17-demethoxygeldanamycin (an inhibitor of heat shock protein 90) reduced the endogenous expression levels of P-gp in the human colorectal cancer cells, HCT-15 and SW620-14. In contrast, inhibitors of phosphatidylinositol 3-OH kinase, mammalian target of rapamycin, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase did not affect P-gp expression in these cells. We further found that U0126 down-regulated exogenous P-gp expression in the MDR1-transduced human breast cancer cells, MCF-7/MDR and MDA-MB-231/MDR. However, the MDR1 mRNA levels in these cells were unaffected by this treatment. PD98059 (a MEK inhibitor), ERK small interfering RNA, and p90 ribosomal S6 kinase (RSK) small interfering RNA also suppressed P-gp expression. Conversely, epidermal growth factor and basic fibroblast growth factor enhanced P-gp expression, but the MDR1 mRNA levels were unchanged in epidermal growth factor–stimulated cells. Pulse-chase analysis revealed that U0126 promoted P-gp degradation but did not affect the biosynthesis of this gene product. The pretreatment of cells with U0126 enhanced the paclitaxel-induced cleavage of poly(ADP-ribose) polymerase and paclitaxel sensitivity. Furthermore, U0126-treated cells showed high levels of rhodamine123 uptake. Hence, our present data show that inhibition of the MEK-ERK-RSK pathway down-regulates P-gp expression levels and diminishes the cellular multidrug resistance. [Mol Cancer Ther 2007;6(7):2092–2102]
ZD4054, a specific antagonist of the endothelin A receptor, inhibits tumor growth and enhances paclitaxel activity in human ovarian carcinoma in vitro and in vivo
Authors: Rosanò Laura , Di Castro Valeriana , Spinella Francesca , Nicotra Maria Rita , Natali Pier Giorgio , Bagnato Anna
Published: July 2007

The autocrine endothelin (ET)-1/endothelin A receptor (ETAR) pathway is an important regulator of several processes involved in ovarian cancer progression, and its overexpression is associated with aggressive disease. These features have led to the proposal of the ETAR receptor as a potential target for improving ovarian cancer treatment. In this study, we evaluated in vitro and in vivo the effects of ZD4054, an orally active antagonist that specifically binds ETAR, as monotherapy, and in combination with paclitaxel. In the human ovarian cancer ETAR-positive cell lines HEY, OVCA 433, SKOV-3, and A-2780, ZD4054 effectively inhibited the basal and ET-1–induced cell proliferation, associated with the inhibition of AKT and p42/44MAPK phosphorylation, and with increased apoptosis, through the inhibition of bcl-2 and activation of caspase-3 and poly(ADP-ribose) polymerase proteins. ZD4054 treatment also resulted in a reduction of ETAR-driven angiogenesis and invasive mediators, such as vascular endothelial growth factor, cyclooxygenase-1/2, and matrix metalloproteinase (MMP). The combination of ZD4054 and paclitaxel led to the potentiation of all these effects, indicating that ZD4054, by blocking the ETAR-dependent proliferative, invasive, and antiapoptotic signals, can enhance sensitivity to paclitaxel. In HEY ovarian cancer xenografts, ZD4054 significantly inhibited tumor growth to the same degree as paclitaxel. Furthermore, ZD4054-dependent tumor growth inhibition was associated with a reduction in proliferation index, microvessel density, and MMP-2 expression. Interestingly, the combination of ZD4054 and paclitaxel produced additive antitumor effects, with 40% of mice remaining tumor-free, supporting a rationale for the clinical use of ZD4054 as monotherapy or in combination with cytotoxic drugs. [Mol Cancer Ther 2007;6(7):2003–11]
Cross-Cultural Negotiating: A Japanese-American Case Study from Higher Education
Authors: Prestwich Roger
Published: July 2007

This article discusses a cross-cultural negotiation process between a new Japanese university and an established American university to create a joint business venture – a dual-degree program. The parties failed to sign a contract, and there were indicators during negotiations pointing to the likelihood of a failed outcome. Negotiation style convergence was evident, with the Japanese adopting an erabi ('either-or') style and the Americans an awase ('more-or-less') style. The 7-Step framework used to structure the negotiation discussion may be better suited to analyzing Japanese negotiation processes than American. The implications will be of value to Japanese and American/Western businesspeople or educational administrators involved in joint venture-type negotiations.
The Road To Helsinki: The Aceh Agreement and Indonesia's Democratic Development
Authors: Morfit Michael
Published: July 2007

Despite considerable skepticism, the August 2005 Helsinki agreement between the Government of Indonesia and Free Aceh Movement were largely successful in resolving nearly 30 years of armed conflict. The December 2006 local elections are now widely recognized as marking the consolidation of that peace agreement. Conventional accounts of the Helsinki negotiations do not capture the complexity and richness of the various political, military, institutional and personal forces at play. A closer examination reveals the extent to which the Helsinki Memorandum of Understanding was a key milestone in Indonesia's continuing democratic development.
Are Needs to Manage Uncertainty and Threat Associated With Political Conservatism or Ideological Extremity?
Authors: Jost John T. , Napier Jaime L. , Thorisdottir Hulda , Gosling Samuel D. , Palfai Tibor P. , Ostafin Brian
Published: July 2007

Three studies are conducted to assess the uncertainty— threat model of political conservatism, which posits that psychological needs to manage uncertainty and threat are associated with political orientation. Results from structural equation models provide consistent support for the hypothesis that uncertainty avoidance (e.g., need for order, intolerance of ambiguity, and lack of openness to experience) and threat management (e.g., death anxiety, system threat, and perceptions of a dangerous world) each contributes independently to conservatism (vs. liberalism). No support is obtained for alternative models, which predict that uncertainty and threat management are associated with ideological extremism or extreme forms of conservatism only. Study 3 also reveals that resistance to change fully mediates the association between uncertainty avoidance and conservatism, whereas opposition to equality partially mediates the association between threat and conservatism. Implications for understanding the epistemic and existential bases of political orientation are discussed.
Similar or Different? The Importance of Similarities and Differences for Support Between Siblings
Authors: Voorpostel Marieke , van der Lippe Tanja , Dykstra Pearl A. , Flap Henk
Published: July 2007

Using a large-scale Dutch national sample ( N = 7,126), the authors examine the importance of similarities and differences in the sibling dyad for the provision of support. Similarities are assumed to enhance attraction and empathy; differences are assumed to be related to different possibilities for exchange. For helping with housework, helping with odd jobs, giving advice, and showing interest, logistic regression models are estimated and similarities and differences in gender, age, educational level, partner status, and whether the siblings have children are examined. The authors find only limited corroboration for the relevance of similarities, both siblings being sisters, or both being childless. Validation for the importance of differences is found, relating to different roles. For instance, older siblings are more supportive toward their younger siblings than the other way around, and the childless support their parenting siblings, especially in young adulthood.
Variation Among Siblings in the Use of a Non–English Language
Authors: Stevens Gillian , Ishizawa Hiromi
Published: July 2007

As the concept of “mother-tongue shift,” which explicitly compares the first languages learned and spoken by parents and their children, suggests, the language repertoires of family members may differ across generations. In this study, the authors consider the possibility that language repertoires differ within the same generation. The results, based on recent Current Population Survey data, first show that the language repertoires of siblings are sometimes different, demonstrating that instances of mother-tongue shift and mother-tongue retention can occur within the same family. The authors also find that the odds of children speaking a non–English language vary according to the sibling position of the child within the household. The eldest child is more likely to speak a minority language than later-born children. Moreover, children's language repertoires are influenced by their siblings' characteristics.
Attitudes About Childlessness in the United States
Authors: Koropeckyj-Cox Tanya , Pendell Gretchen
Published: July 2007

The study used cross-sectional analyses of the National Survey of Families and Households (1987-1988, 1992-1994) to examine attitudes about childlessness in the United States. It (a) assesses prevalence of positive, neutral, and negative attitudes about childlessness and (b) identifies the correlates of different attitudes in the population. About one fifth of adults disagreed with prescriptive norms that favor parenthood over childlessness, whereas two fifths gave neutral responses. More than 86% agreed or were neutral on whether childless adults could have fulfilling lives. Positive attitudes were consistently found among those who were female, college educated, or childless. Those with negative attitudes were distinct from those with neutral or positive attitudes and were more likely to be older, male, non-White, less educated, or have conservative religious beliefs, net of other factors. The authors argue attitudes reflect acceptance but not endorsement of childlessness, and substantial proportions of neutral responses merit closer examination.
Long-Term Enzyme Replacement Therapy for Pompe Disease With Recombinant Human Alpha-glucosidase Derived From Chinese Hamster Ovary Cells
Authors: Rossi Massimiliano , Parenti Giancarlo , Della Casa Roberto , Romano Alfonso , Mansi Giuseppina , Agovino Teresa , Rosapepe Felice , Vosa Carlo , Del Giudice Ennio , Andria Generoso
Published: July 2007

Pompe disease is a rare autosomal recessive myopathy due to the deficiency of lysosomal acid alpha-glucosidase. Clinical phenotypes range from the severe classic infantile form (hypotonia and hypertrophic cardiomyopathy), to milder late onset forms (skeletal myopathy and absence of significant heart involvement). Enzyme replacement therapy with recombinant human alpha-glucosidase derived from either rabbit milk or Chinese hamster ovary cells has been introduced and is undergoing clinical trials. Reported is a long-term follow-up of 3 Pompe patients presenting without cardiomyopathy, treated with recombinant human alpha-glucosidase derived from Chinese hamster ovary cells. This study suggests that enzyme replacement therapy can lead to significant motor and respiratory improvement in the subgroup of patients who start the therapy before extensive muscle damage has occurred. The recombinant enzyme derived from Chinese hamster ovary cells, administered at doses significantly higher than previously reported, appears to have the same safety as the drug derived from rabbit milk.
Factors Associated With Epilepsy in Children With Periventricular Leukomalacia
Authors: Humphreys Peter , Deonandan Raywat , Whiting Sharon , Barrowman Nick , Matzinger Mary-Ann , Briggs Valerie , Hurteau Julie , Wallace Eda
Published: July 2007

Children with cerebral palsy associated with periventricular leukomalacia frequently develop unprovoked epileptic seizures. This article reports an analysis of risk factors for epilepsy in children with radiologically confirmed periventricular leukomalacia. This cohort was screened for epilepsy and for an array of clinical and demographic factors. Of 154 subjects with radiologically confirmed periventricular leukomalacia, 40 (26.0%) had epilepsy. In the epileptic group, radiologic pathology other than periventricular leukomalacia was uncommon. Significant associations were found between epilepsy and cerebral palsy patterns other than spastic diparesis, mental handicap, cortical visual impairment, neonatal seizures, and severe periventricular leukomalacia. Only the presence of neonatal seizures was significantly associated with epilepsy once other risk factors were controlled in the regression model. Some previous studies have shown an association between neonatal seizures and later epilepsy for cerebral palsy in general. This is the first report of such an association for a single predominant type of cerebral pathology.
Lamotrigine Overdose in a Child
Authors: Daana Muhannad , Nevo Yoram , Tenenbaum Ariel , Taustein Illana , Berger Itai
Published: July 2007

The purpose of this article is to describe an unusual presentation of lamotrigine toxicity in an epileptic child treated on a lower than previously reported dosage. This is a case description of a 5-year-old epileptic girl on lamotrigine monotherapy, which caused toxicity. The child presented with ataxia, drowsiness, and acute confusion after ingesting 500 mg (25 mg/kg/d) in two 250-mg doses 12 hours apart. This was followed by vomiting and seizure exacerbation. Discontinuing lamotrigine, intravenous fluids and observation were the mainstays of therapy. Until now, the reported minimum dose of lamotrigine causing toxicity was 800 mg. In this patient, toxic manifestation occurred after the initial 250 mg. This case report demonstrates the low safety margin in children treated with lamotrigine.
Prospective Open-Label Clinical Trial of Trihexyphenidyl in Children With Secondary Dystonia due to Cerebral Palsy
Authors: Sanger Terence D. , Bastian Amy , Brunstrom Jan , Damiano Diane , Delgado Mauricio , Dure Leon , Gaebler-Spira Deborah , Hoon Alec , Mink Jonathan W. , Sherman-Levine Sara , Welty Leah J. ,   the Child Motor Study Group
Published: July 2007

Although trihexyphenidyl is used clinically to treat both primary and secondary dystonia in children, limited evidence exists to support its effectiveness, particularly in dystonia secondary to disorders such as cerebral palsy. A prospective, open-label, multicenter pilot trial of high-dose trihexyphenidyl was conducted in 23 children aged 4 to 15 years with cerebral palsy judged to have secondary dystonia impairing function in the dominant upper extremity. All children were given trihexyphenidyl at increasing doses over a 9-week period up to a maximum of 0.75 mg/kg/d. Trihexyphenidyl was subsequently tapered off over the next 5 weeks. Objective motor assessments were performed at baseline, 9 weeks, and 15 weeks. The primary outcome measure was the Melbourne Assessment of Unilateral Upper Limb Function, tested in the dominant arm. Tolerability and safety were monitored closely throughout the trial. Of the 31 children who agreed to participate in the study, 5 failed to meet entry criteria and 3 withdrew due to nonserious adverse events (chorea, drug rash, and hyperactivity). Three children required a dosage reduction because of nonserious adverse events but continued to participate. The 23 children who completed the study showed a significant improvement in arm function at 15 weeks ( P = .045) but not at 9 weeks ( P = .985). Post hoc analysis showed that a subgroup (n = 10) with hyperkinetic dystonia (excess involuntary movements) worsened at 9 weeks ( P = .04) but subsequently returned to baseline following taper of the medicine. The authors conclude that scientific evidence for the clinical use of trihexyphenidyl in cerebral palsy remains equivocal. Trihexyphenidyl may be a safe and effective for treatment for arm dystonia in some children with cerebral palsy if given sufficient time to respond to the medication. Post hoc analyses based on the type of movement disorder suggested that children with hyperkinetic forms of dystonia may worsen. A larger, randomized prospective trial stratified by the presence or absence of hyperkinetic movements is needed to confirm these results.
Levetiracetam-Induced Diffuse Interstitial Lung Disease
Authors: Newsome Scott D. , Xue Lanny Y. , Jennings Timothy , Castaneda Glenn Y.
Published: July 2007

The authors report the first case of levetiracetam-induced diffuse interstitial lung disease. The patient is a 9-year-old girl who was admitted to the pediatric intensive care unit for aspiration pneumonia. She has a history of epilepsy, cerebral palsy, mental retardation, asthma, and repeated hospitalizations for presumed aspiration pneumonia, which resolved with conventional medical treatment. She has been on low-dose levetiracetam for her epilepsy over the past 2 years, and the dosage was increased just prior to this admission. However, this time, with conventional treatment, the patient's aspiration pneumonia did not improve, which led to a lung biopsy. The biopsy demonstrated a diffuse interstitial process of relatively recent onset, with features consistent with diffuse lung disease. Levetiracetam was implicated in the pathogenesis of the interstitial pneumonitis. The patient improved clinically after the discontinuation of levetiracetam and with the treatment of steroids.
Neurodevelopmental Outcome After Severe Traumatic Brain Injury in Very Young Children: Role for Subcortical Lesions
Authors: Bonnier Christine , Marique Patricia , Van Hout Anne , Potelle Dominique
Published: July 2007

Traumatic brain injury is a major cause of mortality and morbidity in children younger than 15 years of age. To evaluate the role of subcortical lesions on neurodevelopmental outcomes, long-term outcomes of 50 children with severe traumatic brain injury before 4 years of age (accidental injury, n = 21, nonaccidental injury, n = 29) were reviewed retrospectively and compared with late magnetic resonance imaging (MRI) findings: no visible lesions, cortical lesions, or subcortical lesions. Subcortical lesions occurred in both accidental and nonaccidental traumatic brain injuries. Traumatic brain injury severity (initial Glasgow Coma Scale or coma duration) was significantly associated with subcortical lesions. Long-term motor or visual deficiencies occurred in one third of patients and cognitive deficiencies in 52.1%. Although deficiencies occurred without visible MRI lesions, global outcome scores, motor delay, visual impairment, head growth slowing, global intellectual quotients, and planning performances were significantly worse in patients with subcortical lesions. An alarming deterioration in intellectual quotient over time was noted. It was concluded that neurodevelopmental outcomes are worrisome after severe traumatic brain injury in young children, and subcortical lesions affect the prognosis.
Neurodevelopmental Outcome of Children With Intrauterine Growth Retardation: A Longitudinal, 10-Year Prospective Study
Authors: Leitner Yael , Fattal-Valevski Aviva , Geva Ronny , Eshel Rina , Toledano-Alhadef Hagit , Rotstein Michael , Bassan Haim , Radianu Bella , Bitchonsky Ora , Jaffa Ariel J. , Harel Shaul
Published: July 2007

One hundred twenty-three children with intrauterine growth retardation were prospectively followed from birth to 9 to 10 years of age in order to characterize their specific neurodevelopmental and cognitive difficulties and to identify clinical predictors of such difficulties. Perinatal biometric data and risk factors were collected. Outcome was evaluated at age 9 to 10 by neurodevelopmental, cognitive, and school achievement assessments. Sixty-three children served as controls who were appropriate for gestational age. Significant differences in growth ( P < .001), neurodevelopmental scores ( P < .001), intelligence quotient (IQ) ( P < .0001), and school achievements measured by the Kaufmann Assessment Battery for Children ( P < .001) were found between the children with intrauterine growth retardation and controls. Children with intrauterine growth retardation demonstrated a specific profile of neurocognitive difficulties at school age, accounting for lower school achievements. The best perinatal parameter predictive of neurodevelopment and IQ was the Cephalization Index ( P < .001). Somatic catch-up growth at age 2 and at age 9 to 10 correlated with favorable outcome at 9 to 10 years of age.
Current Treatment of West Syndrome in Japan
Authors: Tsuji Takeshi , Okumura Akihisa , Ozawa Hiroshi , Ito Masatoshi , Watanabe Kazuyoshi
Published: July 2007

About 10 years have passed since a previous survey on the treatment of West syndrome in Japan. To elucidate current practice, a questionnaire was sent to 113 institutes. It included (1) the drugs used for the treatment, (2) their dosage, and (3) the dosage and the schedule of adrenocorticotropic hormone therapy. Response rate was 51.3%. Adrenocorticotropic hormone, valproic acid, vitamin B6, and zonisamide were frequently used. Vitamin B6 was used most frequently as the first-choice drug followed by valproic acid, zonisamide, and adrenocorticotropic hormone. The most frequently used dose of synthetic adrenocorticotropic hormone-Z was 0.0125 mg/kg/d. Adrenocorticotropic hormone was administered every day for 2 weeks and then tapered off in more than 80% of the institutes. Although therapeutic strategy and drug usage have not changed largely during these 10 years, 2 alterations were observed: an increased use of zonisamide and a shortened duration of adrenocorticotropic hormone therapy.
Childhood Epilepsy With Occipital Paroxysms: Difficulties in Distinct Segregation Into Either the Early-Onset or Late-Onset Epilepsy Subtypes
Authors: Genizi Jacob , Zelnik Nathanel , Ravid Sarit , Shahar Eli
Published: July 2007

The Commission on Classification and Terminology of the International League Against Epilepsy Childhood rigidly segregated epilepsy with occipital paroxysms into 2 separate syndromes with different predominant seizure types: early-onset seizure susceptibility type consisting of prolonged infrequent, nocturnal autonomic seizures and accompanied by eye deviation and ictal vomiting and late onset with short diurnal frequent seizures and visual ictal manifestations along with throbbing headaches. Epileptic clinical manifestations and electroencephalographic data were analyzed in 28 patients with suspected occipital lobe epilepsy in an attempt to segregate them into either the early or late forms according to the International League Against Epilepsy classification. Electroencephalography in 25 children demonstrated occipital epileptiform paroxysms compatible with the suspected epileptic syndrome. Only 14 (50%) children complied with the rigid criteria of either early-onset or late-onset presentations. The other 14 (50%) children presented with mixed diverse epileptic phenomena such as short-lived seizures in infancy or prolonged seizures during childhood, not complying with either rigid syndrome (ie, short-lived epileptic blindness at an early age or vomiting during later childhood). Despite present attempts to rigidly segregate childhood epilepsy with occipital paroxysms into 2 distinct epileptic syndromes, a high percentage of children still present with various mixed clinical phenomena. Therefore, clinicians should be aware of possible unique and unusual presentations of occipital lobe epilepsy at various ages.
Poor Penmanship in Children Correlates With Abnormal Rhythmic Tapping: A Broad Functional Temporal Impairment
Authors: Ben-Pazi Hilla , Kukke Sahana , Sanger Terence D.
Published: July 2007

Timing is crucial for proficient motor tasks; temporal impairments may lead to dysfunctional motor activities. Although much research has been dedicated to the study of movement timing, clinical examination often overlooks temporal impairment of motor activity. The authors hypothesize that some children have a global temporal impairment leading to dysfunctional motor skills. This article checks whether temporal abnormalities detected on a simple tapping task correlate with temporal dysfunction during complex motor skills such as handwriting. Twenty-three school-aged children, 8-14 years (11.1 ± 1.3 years), underwent tests to assess finger tapping and cursive handwriting. Handwriting samples were rated by experienced teachers. Children with abnormal tapping had lower handwriting rating scores. Temporal features were similar in both tasks; variability on the tapping test correlated with handwriting variability. Temporal variability was not significantly higher for children with poor penmanship as a whole but rather specific to the subgroup of children with a tapping abnormality. Poor penmanship could be attributed in certain children to global temporal impairment reflected as variable finger tapping and handwriting. Evaluation of dysfunctional motor performance should include temporal aspects, and further studies are needed to better delineate and address treatment of “dysrhythmia.”
Memantine as Adjunctive Therapy in Children Diagnosed With Autistic Spectrum Disorders: An Observation of Initial Clinical Response and Maintenance Tolerability
Authors: Chez Michael G. , Burton Quinn , Dowling Timothy , Chang Mina , Khanna Pavan , Kramer Christopher
Published: July 2007

Autism and Pervasive Developmental Disorder Not Otherwise Specified are common developmental problems often seen by child neurologists. There are currently no cures for these lifelong and socially impairing conditions that affect core domains of human behavior such as language, social interaction, and social awareness. The etiology may be multifactorial and may include autoimmune, genetic, neuroanatomic, and possibly excessive glutaminergic mechanisms. Because memantine is a moderate affinity antagonist of the N-methylD-aspartic acid (NMDA) glutamate receptor, this drug was hypothesized to potentially modulate learning, block excessive glutamate effects that can include neuroinflammatory activity, and influence neuroglial activity in autism and Pervasive Developmental Disorder Not Otherwise Specified. Open-label add-on therapy was offered to 151 patients with prior diagnoses of autism or Pervasive Developmental Disorder Not Otherwise Specified over a 21-month period. To generate a clinician-derived Clinical Global Impression Improvement score for language, behavior, and self-stimulatory behaviors, the primary author observed the subjects and questioned their caretakers within 4 to 8 weeks of the initiation of therapy. Chronic maintenance therapy with the drug was continued if there were no negative side effects. Results showed significant improvements in open-label use for language function, social behavior, and self-stimulatory behaviors, although self-stimulatory behaviors comparatively improved to a lesser degree. Chronic use so far appears to have no serious side effects.
Late-Infantile Neuronal Ceroid Lipofuscinosis (CLN2/Jansky-Bielschowsky Type) in Oman
Authors: Koul Roshan , Al-Futaisi Amna , Ganesh Anuradha , Rangnath Bushnarmuth Shivayogi
Published: July 2007

This study was conducted to see the pattern of neuronal ceroid lipofuscinosis in Oman. Eleven children (10 male) with late-infantile neuronal ceroid lipofuscinosis were seen in 5 families. Most of the patients, 9 of 11 (81.8%), were CLN2 type (late-infantile neuronal ceroid lipofuscinosis or Jansky-Bielschowsky), and 2 patients were the atypical type. Five children were seen in 1 extended family. All children had onset with seizures except in 1 family. The majority had onset between ages 1 to 4 years. Nine and of the 11 children had onset with myoclonic seizures. Neuroregression and microcephaly were noted in all. All children had brain volume reduction and typical cerebellar atrophy. Ophthalmological examination was abnormal in all. Clinical features, histological findings, and genetic study reveal that CLN2 type is the most common form of neuronal ceroid lipofuscinosis. There is male predominance of 90.1% in this part of the Arab world.
Costello Syndrome: Cognitive and Proton Magnetic Resonance Spectroscopy Findings—A Case Report
Authors: Perniola Tommaso , Dicuonzo Franca , Margari Lucia , Presicci Anna , Ventura Patrizia , Palma Michele , Carella Aristide
Published: July 2007

The authors describe a girl with Costello syndrome who showed cerebral palsy and neurosensorial deafness. Brain computer tomography and magnetic resonance findings were normal. Multivoxel proton magnetic resonance spectroscopy showed a lowering of the peak of choline with a reduced choline/creatine ratio at the level of the centrum semiovale. These findings might be due to a congenital dysmyelinating or hypomyelinating condition. A complete neuroimaging study can play a relevant role to better clarify the pathogenesis of brain involvement in Costello syndrome.
Methylation Status in Females With Rett Syndrome
Authors: Freilinger Michael , Kalisch David , Muehl Adolf , Haas Oskar , Moritz Anne , Bodamer Olaf
Published: July 2007

The authors studied methionine and creatine metabolism in females with Rett syndrome. Plasma metabolites (including methionine, homocysteine, guanidinoacetate) and urine creatine/creatinine ratios in 29 females with Rett syndrome were within the age-appropriate range. Although the authors have not been able to identify any abnormalities, it can be speculated that patients with Rett syndrome may benefit from dietary intervention to increase the supply of labile methyl groups to affected tissues.