bluuebunny/crossref_metadata_2025 huggingface dataset:
The Cyclooxygenase‐2 Selective Inhibitor Celecoxib Suppresses Proliferation and Invasiveness in the Human Oral Squamous Carcinoma
Authors: KWAK YOUNG EUN , JEON NAM KYEOUNG , KIM JIN , LEE EUN JU
Published: April 2007

Abstract:  Cyclooxygenease‐2 (COX‐2) expression is a critical factor in inflammation, and plays an important role in defense against exogenous stimuli, while overexpression of COX‐2 causes cells to exhibit changes in tumor phenotype. This article attempted to determine the mechanisms underlying the chemopreventive effects of celecoxib on cellular level events, in order to characterize the effects of celecoxib with regard to human oral squamous cell carcinoma (OSCC) cell growth and invasion/migration. In order to determine COX‐2 expression levels, we used an OSCC cell line established from surgically resected specimens of an untreated primary OSCC of the tongue, and used reverse transcription‐polymerase chain reaction (RT‐PCR) and Western blot analyses with anti‐COX‐2 monoclonal antibodies. The YD‐10B cells represented a highly invasive OSCC cell line, which was found to express the COX‐2 protein. Celecoxib inhibited the growth of this OSCC cell line, in a time‐ and dose‐dependent manner. This reduction in cell proliferation was associated with the upregulation of the cyclin‐dependent kinase (CDK) inhibitors, p27. In addition, 10 uM celecoxib inhibited cell invasion/migration through the type I collagen matrix by ∼40% within 24 h. The results of zymography reveal that, in the presence of 10 μL celecoxib, both MMP‐2 and MMP‐9 enzyme activity decreased by ∼30–40%. The current in vitro study indicated that the inhibition of proliferation and invasion/migration in OSCC cell line by the COX‐2‐specific inhibitor, celecoxib, results in anticancerous effects via a variety of cellular and molecular mechanisms. This article also supports the notion that the COX‐2 inhibitor may be useful in the inhibition and/or prevention of metastasis.
The Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor ZD1839 (Iressa) Suppresses Proliferation and Invasion of Human Oral Squamous Carcinoma Cells via p53 Independent and MMP, uPAR Dependent Mechanism
Authors: LEE EUN JU , WHANG JIN HA , JEON NAM KYEONG , KIM JIN
Published: April 2007

Abstract:  Oral squamous cell carcinomas (OSCCs) are characterized by a marked propensity for local invasion and dissemination to cervical lymph nodes. Overexpression of the epidermal growth factor receptor (EGFR) and high levels of certain matrix metalloproteinases (MMPs) have been implicated in the development of squamous cell carcinoma of oral cancer. ZD1839 (Iressa) is a quinazoline derivative that selectively inhibits the EGFR tyrosine kinase activity and is clinically used for cancer patients. This article attempted to determine the mechanisms underlying the effects of ZD1839 on the cellular level, and to characterize the effects of ZD1839 with regard to human OSCC cell growth and invasion/migration. The YD‐10B cells represent a highly invasive human OSCC cell line, which has a frame shift p53 mutation. ZD1839 inhibited the growth of the cell line in a time‐ and dose‐dependent manner. Cell cycle kinetic analysis demonstrated that ZD1839 induces a delay in cell cycle progression and a G1 arrest. This induction of a G1 cell cycle arrest was associated with the upregulation of cyclin‐dependent kinase inhibitors (CDKI) p27KIP1 and p21CIP1/WAF1. The upregulation of CDKI in ZD1839 treated cell lines may be mediated by a p53‐independent and hnRNPC1/C2‐dependent pathway. In addition, 100 nM ZD1839 demonstrated that both MMP‐2 and MMP‐9 enzyme activity were decreased by ∼25–30%. Reverse transcription‐polymerase chain reaction (RT‐PCR) analysis showed that ZD1839 downregulated the uPAR mRNA level. These results might be associated with the reduction of MMP‐2 and MMP‐9 activities. The current in vitro study indicates that the inhibition of proliferation and invasion/migration in OSCC cell lines by ZD1839 results in an anticancer effect via multiple cellular and molecular mechanisms, and suggests that ZD1839 may be useful in inhibiting and/or preventing metastasis.
Increased Cyclooxygenase‐2 Expression Associated with Inflammatory Cellular Infiltration in Elderly Patients with Vulvar Cancer
Authors: LEE TAEK SANG , JEON YONG TARK , KIM JAE WEON , WON JAE KYUNG , PARK NOH HYUN , PARK IN AE , JUHNN YONG SUNG , KANG SOON BEOM , LEE HYO PYO , SONG YONG SANG
Published: April 2007

Abstract:  As the relationship between inflammation and carcinogenesis grows stronger, the role of cyclooxygenase‐2 (COX‐2) and epidermal growth factor (EGFR) has been highlighted in the pathogenesis and progression of human cancer. In view of the fact that vulvar cancer is characterized by precancerous inflammatory changes in elderly patients, the expressions of COX‐2 and EGFR are expected to show different patterns of distribution according to age and other prognostic factors. To verify whether there was a relationship between their expression and clinicopathologic parameters in vulvar cancer, we investigated the inflammatory cellular infiltration and the expression of COX‐2 and EGFR by immunohistochemical analysis. Eleven of 19 samples (57.8%) were stained positive for COX‐2, and 17 (89.4%) for EGFR. The portion of inflammatory cellular infiltration in adjacent normal tissue was also higher in the older age group, and showed a strong correlation with COX‐2 positivity (P= 0.002). Furthermore, COX‐2 expression was significantly more frequent in patients over 60 years of age compared to those under 50 years (P= 0.009). COX‐2 expression was noted to be high in moderate and well‐differentiated cases, whereas, poorly differentiated carcinoma was negative for COX‐2 expression (P= 0.023). However, EGFR expression was not differently distributed on the basis of stage, age, tumor grading, or presence of lymph node metastasis. Our article suggests that vulvar cancer in elderly patients may be associated with inflammation, and thus with increased COX‐2 expression. In light of these findings, a clinical trial designed to assess the addition of COX‐2 targeted therapy to conventional treatment in vulvar cancer would be helpful for consideration of additional treatment options and possibly avoiding the serious surgical morbidity in elderly patients.
Immune Complexes Induce Monocyte Survival through Defined Intracellular Pathways
Authors: BIANCHI GIORDANO , MONTECUCCO FABRIZIO , BERTOLOTTO MARIA , DALLEGRI FRANCO , OTTONELLO LUCIANO
Published: April 2007

Abstract:  Monocytes recruitment and survival at sites of inflammation are determinant for the persistence of inflammatory reactions. Immune‐complexes (ICs), whose tissue deposition is involved in a variety of autoimmune diseases, activate monocytes through the interaction with Fcγ‐receptor triggering the secretion of several inflammatory modulators and favoring their tissue accumulation by inhibiting the apoptosis. To elucidate the intracellular pathways governing this process, on the basis of our previous findings regarding the dose‐dependent inhibition of apoptosis in IC‐activated monocytes, we have investigated the role of PI3K/Akt pathway, MAP kinases, nuclear factor‐κB (NF‐κB), and caspase 3, 8, and 9. Here we show that IC‐activated monocytes underwent apoptosis at a rate comparable to that of resting monocytes in the presence of LY294002, a selective inhibitor of PI3K, as well in the presence of Akt inhibitor, PD98059 inhibitor of ERK1/2, and SB203580 inhibitor of p38. Moreover, IC‐triggered phosphorylation of Akt, ERK1/2, and p38 MAP kinase was demonstrated on Western blot analysis. SN50, an inhibitor of NF‐κB translocation and BMS345541, a specific inhibitor of IKK, also abolished the apoptosis protection conferred by ICs. In parallel, ICs induced an increase in NF‐κB activation, as shown by EMSA, together with the expression of XIAP, as shown by Western blot, though indicating that in monocytes IC protection from apoptosis is NF‐κB dependent. Finally, the activity of caspase 3, 8, and 9 resulted inhibited in IC‐activated monocytes. These results disclose a signaling route triggered by ICs which can be involved in the pathophysiology of inflammatory diseases and can represent a target for therapy of IC‐mediated diseases.
Resveratrol Induces Apoptosis in Chemoresistant Cancer Cells via Modulation of AMPK Signaling Pathway
Authors: HWANG JIN‐TAEK , KWAK DONG WOOK , LIN SUN KYO , KIM HYE MIN , KIM YOUNG MIN , PARK OCK JIN
Published: April 2007

Abstract:  Resveratrol has been reported to possess therapeutic effects for various cancers including colon cancers. In this article, the molecular basis of resveratrol with emphasis on its ability to control intracellular signaling cascades of adenosine monophosphate (AMP)‐activated protein kinase (AMPK) responsible for inducing apoptosis in drug‐resistant cancer cells was investigated.
Recently, the evolutionarily conserved serine/threonine kinase, AMPK, emerges as a possible target molecule of cancer control. We have investigated the effects of resveratrol on apoptosis in relation to AMPK in HT‐29 cells shown chemoresistant to a cancer chemotherapeutic drug, etoposide. Resveratrol exhibited a variety of molecular events in etoposide‐based combination therapy in HT‐29 colon cancer cells including the AMPK activation, inhibition of cell growth, induction of apoptosis, and reactive oxygen species (ROS) generation. The involvement of AMPK signaling cascade in resveratrol‐based cancer therapy was clearly shown by comparing the conditions of AMPK activated states and inactivated states. We have identified ROS as an upstream regulator of AMPK. Further investigation warrants to elucidate the mechanism by which resveratrol generates ROS and AMPK activation.
Epigallocatechin Gallate Inhibits Phorbol Ester‐Induced Activation of NF‐κB and CREB in Mouse Skin
Authors: KUNDU JOYDEB KUMAR , SURH YOUNG‐JOON
Published: April 2007

Abstract: The modulation of intracellular signaling network involved in an inappropriate expression of cyclooxygenase‐2 (COX‐2) is a pragmatic approach for chemoprevention with a wide variety of dietary phytochemicals. Epigallocatechin gallate (EGCG), a major green tea polyphenol, is one of the most extensively investigated chemopreventive agents. Our previous study revealed that EGCG inhibited expression of COX‐2 and activation of mitogen‐activated protein kinases (MAPKs) in mouse skin stimulated with a prototype tumor promotor 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA). This study was aimed at identifying transcription factors as molecular targets of EGCG in downregulating COX‐2 expression. We found that EGCG inhibited TPA‐induced DNA binding of NF‐κB and CREB in mouse skinin vivo. EGCG also suppressed TPA‐induced phosphorylation and subsequent degradation of IκBα, and prevented nuclear translocation of p65. We also examined whether extracellular signal‐regulated protein kinase (ERK) and p38 MAPK, which are known to regulate activation of NF‐κB, can also modulate CREB DNA binding. Pretreatment with U0126 and SB203580, pharmacological inhibitors of ERK and p38 MAPK, respectively, showed that SB203580, but not U0126, attenuated TPA‐induced CREB DNA binding in mouse skin. Taken together, EGCG inhibited TPA‐induced DNA binding of NF‐κB and CREB by blocking activation of p38 MAPK, which may provide a molecular basis of COX‐2 inhibition by EGCG in mouse skinin vivo.
Wogonin, a Plant Flavone, Potentiates Etoposide‐Induced Apoptosis in Cancer Cells
Authors: LEE EIBAI , ENOMOTO RIYO , SUZUKI CHIE , OHNO MASATAKA , OHASHI TOSHINORI , MIYAUCHI AZUSA , TANIMOTO ERIKO , MAEDA KAORI , HIRANO HIROYUKI , YOKOI TOSHIO , SUGAHARA CHIYOKO
Published: April 2007

Abstract: Etoposide, a podophylotoxin anticancer agent, induces apoptotic cell death in normal and cancer cells. Etoposide‐induced apoptosis plays a role in not only anticancer effect but also adverse reaction, such as myelosuppression. Since we have found that wogonin, a flavone found inScutellaria baicalensisGeorgi, prevents thymocyte apoptosis induced by various compounds including etoposide, we examined the effect of this flavone on etoposide‐induced apoptosis in cancer cells. Although 100 μM wogonin itself significantly increased DNA fragmentation in HL‐60 cells, this change was not observed in Jurkat cells. On the other hand, this flavone significantly potentiated etoposide‐induced apoptosis in Jurkat and HL‐60 cells. Similarly, wogonin accelerated etoposide‐induced cell death in lung cancer cells. Since wogonin had no effect on the action of other anticancer agents, such as 5‐FU and cisplatin, this flavone seems to accelerate only etoposide‐induced apoptotic cell death in cancer cells. These results suggest that the modification of etoposide‐induced apoptosis by wogonin may be available to reduce the adverse reaction of this agent.
Resveratrol Inhibits IL‐1β–Induced Stimulation of Caspase‐3 and Cleavage of PARP in Human Articular Chondrocytes in Vitro
Authors: SHAKIBAEI MEHDI , JOHN THILO , SEIFARTH CLAUDIA , MOBASHERI ALI
Published: April 2007

Abstract:  Resveratrol is a polyphenolic phytoalexin that is present in various fruits, in the skin of red grapes and peanuts. Recent studies have shown that resveratrol exhibits potent antioxidant properties and is able to exert anti‐inflammatory and anti‐catabolic properties in several cell types. The pro‐inflammatory cytokine interleukin‐1β (IL‐1β) plays a pivotal role in the pathogenesis of osteoarthritis (OA) in humans and animals. In this article we investigated whether resveratrol is able to block the effects of IL‐1β, specifically the activation of caspase‐3 and subsequent cleavage of poly (ADP‐ribose) polymerase (PARP) in human articular chondrocytes. Cultures of human chondrocytes were prestimulated with 10 ng/mL IL‐1β for 1, 12, and 24 h before being co‐treated with IL‐1β and 100 μM resveratrol or 50 μM of the caspase inhibitor Z‐DEVD‐FMK for 1, 12, and 24 h, respectively in vitro. Resveratrol significantly reduced the IL‐1β‐induced inhibition of expression of cartilage‐specific collagen type II and signal transduction receptor β1‐integrin in a time‐dependent manner. Incubation of chondrocytes with IL‐1β resulted in the activation of caspase‐3 and PARP cleavage. These effects were abolished through co‐treatment with resveratrol. Furthermore, co‐treatment of IL‐1β‐stimulated cells with the caspase inhibitor Z‐DEVD‐FMK blocked activation of caspase‐3 and PARP cleavage, suggesting that this process is a caspase‐dependent pathway. In summary, our results confirm that resveratrol is an effective inhibitor of chondrocyte apoptosis in vitro. These findings suggest that this dietary polyphenolic compound may have future applications in the nutraceutical‐based therapy of human and animal OA.
Assessment of the Effect of Echinacea purpurea (L.) Moench on Apoptotic and Mitotic Activity of Liver Cells during Intoxication by Cadmium
Authors: SMALINSKIENE ALINA , LESAUSKAITE VAIVA , RYSELIS STANISLOVAS , ABDRAKHMANOV OLEG , KREGZDYTE RIMA , SADAUSKIENE ILONA , IVANOV LEONID , SAVICKIENE NIJOLE , ZITKEVIČIUS VIRGILIJUS , SAVICKAS ARUNAS
Published: April 2007

Abstract:  Cadmium (Cd2+) is an important industrial pollutant, although its mechanism of toxicity has not been completely clarified. Cd2+ is toxic to a wide range of organs and tissues, however, the primary target organs of Cd2+ toxicity are the liver and kidney. Echinacea purpurea stimulating one or another tread of the immune system stimulates the expression of immunoglobulins and interferons. The experiments were performed on white laboratory mice using intraperitoneal (i.p.) injections 0.05 LD50 amount of CdCl2 solution. Two groups of mice were injected by Echinacea purpurea liquid extract: one 0.05 LD50 and the other 0.1 LD50. In this article, the Cd2+ distribution in internal organs, its effect on the mitotic and apoptotic activity of liver cells, as well as effects of Echinacea purpurea liquid extract on Cd2+‐induced changes in mice were investigated. Cd2+ concentration in mice blood, liver, and kidney was detected by atomic absorption spectroscopy. Long‐term injections of extract of Echinacea purpurea combined with Cd2+Cl2 leads to the significant increase of Cd2+ concentration in blood and investigated organs of experimental mice. Mitotic and apoptotic activity of liver cells was expressed as the estimated number of mitotic and apoptotic liver cells in randomly selected reference areas in histological slide. Echinacea purpurea decreases the mitotic activity of liver cells induced by Cd2+ and increases apoptotic activity of the liver cells.
Extraosseous Localized Ewing Tumors: Improved Outcome With Anthracyclines—The French Society of Pediatric Oncology and International Society of Pediatric Oncology
Authors: Castex Marie-Pierre , Rubie Hervé , Stevens Michael C.G. , Escribano Carlota Calvo , de Gauzy Jérôme Sales , Gomez-Brouchet Anne , Rey Annie , Delattre Olivier , Oberlin Odile
Published: March 2007

Purpose

To evaluate the outcome of children with an extraosseous Ewing tumor (EOE) according to treatment.

Patients and Methods

Children with EOE were treated either with the strategy used for malignant mesenchymal tumors (MMTs) by the International Society of Pediatric Oncology (SIOP) or with the French Society of Pediatric Oncology (SFOP) regimen used for osseous Ewing tumors (OET). The MMT strategy included vincristine/actinomycin for small and resected tumors or ifosfamide/vincristine/actinomycin for unfavorable sites or unresectable tumors. Surgical excision was to be attempted after four courses, followed by local irradiation in case of residue. Osseous Ewing (OE) protocol included three courses of cyclophosphamide/doxorubicin followed either by two similar courses in case of good response or two courses of ifosfamide/etoposide in case of no response. After resection of the primary, treatment included conventional chemotherapy in case of good histologic response and high-dose chemotherapy and radiotherapy for poor response. All diagnosis specimens were reviewed by the panel.

Results

Between 1989 and 1999, 63 patients were registered. Characteristics of patients treated by both protocols were similar. Five-year overall survival (OS) and event-free survival (EFS) of those treated with the OE protocol are 83% and 75%, respectively, which is significantly better than the OS and EFS of those treated with the MMT strategy (59% and 44%, respectively; P = .04 and .008, respectively). The size of the primary and the type of protocol influenced patients’ EFS. In multivariate analysis, only the regimen had an impact on OS and EFS.

Conclusion

Our study shows that patients with EOE should be treated with OE regimens, probably because of the use of anthracyclines.
Direct-to-Consumer Advertising in Oncology: A Content Analysis of Print Media
Authors: Abel Gregory A. , Lee Stephanie J. , Weeks Jane C.
Published: March 2007

Purpose

Content analysis of cancer-related direct-to-consumer advertising (DTCA), with a focus on how benefit and risk/adverse effect information is presented, is essential to understanding its potential impact on oncology outcomes.

Methods

We reviewed all oncology DTCA appearing in three patient-focused cancer magazines and a sample of selected popular magazines from January 2003 to June 2006. We determined the Flesch reading ease score (FRES) for the text in each advertisement (a score ≥ 65 is readable for the average person). We also assessed the proportion, type size, and placement of benefits and risks/adverse effects, as well as the nature and content of advertising appeals.

Results

Of 284 advertisements identified, 49 were unique. Oncology-related DTCA was rare in the popular magazines, and appeared mostly in those aimed at female readership. About equal amounts of text were devoted to benefits and risks/adverse effects, and all text was difficult to read. The mean FRES for benefit text was 39.71; for risk/adverse effect text, it was 38.22, a difference of 1.49 (95% CI, −4.02 to 7.00). The largest font size for benefits was 4.60 mm on average; for risks/adverse effects, it was 2.38 mm, a difference of 2.22 mm (95% CI, 1.35 to 3.09). Appeals to medication effectiveness were frequent (95%) and often made with clinical trial data (61%).

Conclusion

Oncology print DTCA is prevalent in cancer-related, patient-directed magazines, and infrequent in the popular press. The information presented is considerably difficult to read, raising important questions about the appropriateness of direct-to-consumer marketing for oncologic medications.
Identification of dystroglycan as a second laminin receptor in oligodendrocytes, with a role in myelination
Authors: Colognato Holly , Galvin Jason , Wang Zhen , Relucio Jenne , Nguyen Tom , Harrison David , Yurchenco Peter D. , ffrench-Constant Charles
Published: March 2007

Developmental abnormalities of myelination are observed in the brains of laminin-deficient humans and mice. The mechanisms by which these defects occur remain unknown. It has been proposed that, given their central role in mediating extracellular matrix (ECM) interactions, integrin receptors are likely to be involved. However, it is a non-integrin ECM receptor,dystroglycan, that provides the key linkage between the dystrophin-glycoprotein complex (DGC) and laminin in skeletal muscle basal lamina, such that disruption of this bridge results in muscular dystrophy. In addition, the loss of dystroglycan from Schwann cells causes myelin instability and disorganization of the nodes of Ranvier. To date, it is unknown whether dystroglycan plays a role during central nervous system (CNS)myelination. Here, we report that the myelinating glia of the CNS,oligodendrocytes, express and use dystroglycan receptors to regulate myelin formation. In the absence of normal dystroglycan expression, primary oligodendrocytes showed substantial deficits in their ability to differentiate and to produce normal levels of myelin-specific proteins. After blocking the function of dystroglycan receptors, oligodendrocytes failed both to produce complex myelin membrane sheets and to initiate myelinating segments when co-cultured with dorsal root ganglion neurons. By contrast, enhanced oligodendrocyte survival in response to the ECM, in conjunction with growth factors, was dependent on interactions with beta-1 integrins and did not require dystroglycan. Together, these results indicate that laminins are likely to regulate CNS myelination by interacting with both integrin receptors and dystroglycan receptors, and that oligodendrocyte dystroglycan receptors may have a specific role in regulating terminal stages of myelination, such as myelin membrane production, growth, or stability.
The Association of Depression and Sense of Belonging with Suicidal Ideation Among Older Adults: Applicability of Resiliency Models
Authors: McLaren Suzanne , Gomez Rapson , Bailey Maria , Van Der Horst Renee K.
Published: March 2007

Suicide among older people, especially men, is a significant problem. In this study the applicability of the compensatory, the risk‐protective, the challenge, and the protective‐protective models of resiliency for the prediction of suicidal ideation from depression (the risk factor) and sense of belonging to the community (the protective factor) was investigated. A total of 351 retired Australians (130 males and 221 females), with a mean age of 71.31 years (SD = 7.99), completed the Zung Depression Scale, the suicide subscale of the General Health Questionnaire, and the Sense of Belonging Instrument. When sense of belonging (psychological) was the protective factor, results indicated support for the risk‐protective model for men and women, and for the compensatory model for women only. In contrast, when sense of belonging (antecedents) was the protective factor, support was evident for the compensatory model for men and women, and for the challenge model for women only. Results indicate that interventions should be developed to enhance sense of belonging among aging adults.
Modeling Tonal Tension
Authors: Lerdahl Fred , Krumhansl Carol L.
Published: April 2007

THIS STUDY PRESENTS AND TESTS a theory of tonal tension (Lerdahl, 2001). The model has four components: prolongational structure, a pitch-space model, a surfacetension model, and an attraction model. These components combine to predict the rise and fall in tension in the course of listening to a tonal passage or piece. We first apply the theory to predict tension patterns in Classical diatonic music and then extend the theory to chromatic tonal music. In the experimental tasks, listeners record their experience of tension for the excerpts. Comparisons between predictions and data point to alternative analyses within the constraints of the theory. We conclude with a discussion of the underlying perceptual and cognitive principles engaged by the theory's components.
Association Between Passive Smoking and Infection WithMycobacterium tuberculosisin Children
Authors: den Boon Saskia , Verver Suzanne , Marais Ben J. , Enarson Donald A. , Lombard Carl J. , Bateman Eric D. , Irusen Elvis , Jithoo Anamika , Gie Robert P. , Borgdorff Martien W. , Beyers Nulda
Published: April 2007

OBJECTIVE. Tuberculosis and smoking are both significant public health problems. The association between passive smoking and Mycobacterium tuberculosis infection is not well documented. The objective of this study was to examine the influence of passive smoking on M tuberculosis infection in children.

METHODS. A community survey was conducted in 15% of addresses in 2 adjacent low-income suburbs in Cape Town, South Africa. All children (<15 years of age) and their adult household members residing at these addresses were included in the study. Children underwent tuberculin skin testing. An induration of ≥10 mm was considered to define M tuberculosis infection. Passive smoking was defined as living in the household with at least 1 adult who smoked for at least 1 year. Random-effects logistic regression analysis was performed, and odds ratios were adjusted for age, presence of a patient with tuberculosis in the household, average household income, and clustering at the household level.

RESULTS. Of 1344 children, 432 (32%) had a positive tuberculin skin test. Passive smoking was significantly associated with M tuberculosis infection in the unadjusted analyses but not in the adjusted analyses. In the 172 households with a patient with tuberculosis, passive smoking was significantly associated with a positive tuberculin skin test (but not in the 492 households without a patient with tuberculosis.

CONCLUSIONS. Passive smoking is associated with M tuberculosis infection in children living in a household with a patient with tuberculosis. More studies are needed to confirm this observation, but the possible association is a cause of great concern, considering the high prevalence of smoking and tuberculosis in most developing countries.
Impact of the State Children's Health Insurance Program on Adolescents in New York
Authors: Klein Jonathan D. , Shone Laura P. , Szilagyi Peter G. , Bajorska Alina , Wilson Karen , Dick Andrew W.
Published: April 2007

OBJECTIVES. Adolescents face financial and nonfinancial barriers to health care. Little is known about the impact of health insurance on health care for adolescents. We assessed the impact of New York's State Children's Health Insurance Program on access, use, and quality of care for adolescents.

METHODS. Adolescents and their parents from a stratified random sample of new enrollees in New York's State Children's Health Insurance Program were interviewed by telephone shortly after enrollment (baseline, n = 1118 adolescents and their parents) and 1 year later (follow-up, n = 970). Outcome measures included access (having a usual source of care and reported unmet health needs), use (preventive care and other types of visits), and quality (satisfaction with care, receipt of confidential care and preventive counseling). Outcomes were assessed at baseline (year before the State Children's Health Insurance Program) versus follow-up (year during the State Children's Health Insurance Program).

RESULTS. The proportion of adolescents who reported having a usual source of care increased during State Children's Health Insurance Program compared with before (69.9% to 87.1%). The proportion with any unmet health care need (54.3% to 42.1%) or with unmet need for preventive care (53.8% to 40.6%) decreased, with elimination of racial disparities that existed before the State Children's Health Insurance Program. After enrollment in the State Children's Health Insurance Program, more adolescents reported having had a preventive care visit (65.9% to 74.2%); emergency department use did not change. No differences in satisfaction were noted, although significant increases were noted in both parent- and adolescent-reported rates of having received confidential care and preventive counseling.

CONCLUSIONS. Adolescents who enrolled in New York's State Children's Health Insurance Program experienced improved access, use, and quality of care. These findings suggest that the provision of health insurance can help to improve health care for adolescents.
United Kingdom General Medical Council Fails Child Protection
Authors: Williams Catherine
Published: April 2007

To protect children, pediatricians must be willing to raise the possibility of abuse and not be intimidated by the consequences. We consider that the United Kingdom General Medical Council does not understand child protection matters and has no system for dealing adequately with complaints submitted by parents who claim false allegations of abuse. The actions of the General Medical Council in the recent cases of Drs Roy Meadow and David Southall conflict with current child protection laws and guidance for professionals. By deterring doctors from raising concerns about a child's safety and giving opinions on child deaths, the General Medical Council may be increasing the risk of serious child abuse. Although the rate of registrations by child protection authorities decreased by 28% between 1995 and 2005 (ie, there are fewer multiagency child protection plans), the number of criminal convictions for cruelty to or neglect of a child increased by 247% between 1998 and 2005. It is unacceptable that to date the General Medical Council has refused training in child protection offered by the Royal College of Paediatrics and Child Health.
Reduction of Frequent Otitis Media and Pressure-Equalizing Tube Insertions in Children After Introduction of Pneumococcal Conjugate Vaccine
Authors: Poehling Katherine A. , Szilagyi Peter G. , Grijalva Carlos G. , Martin Stacey W. , LaFleur Bonnie , Mitchel Ed , Barth Richard D. , Nuorti J. Pekka , Griffin Marie R.
Published: April 2007

OBJECTIVE. Streptococcus pneumoniae is an important cause of otitis media in children. In this study we estimated the effect of routine childhood immunization with heptavalent pneumococcal conjugate vaccine on frequent otitis media (3 episodes in 6 months or 4 episodes in 1 year) and pressure-equalizing tube insertions.

PATIENTS AND METHODS. The study population included all children who were enrolled at birth in TennCare or selected upstate New York commercial insurance plans as of July 1998 and continuously followed until 5 years old, loss of health plan enrollment, study outcome, or end of the study. We compared the risk of developing frequent otitis media or having pressure-equalizing tube insertion for 4 birth cohorts (1998–1999, 1999–2000, 2000–2001, and 2001–2002) by using Cox regression analysis. We used data from the National Immunization Survey to estimate the heptavalent pneumococcal conjugate vaccine uptake for children in these 4 birth cohorts in Tennessee and New York.

RESULTS. The proportion of children in Tennessee and New York who received at least 3 doses of heptavalent pneumococcal conjugate vaccine by 2 years of age increased from ≤1% for the 1998–1999 birth cohort to ∼75% for the 2000–2001 birth cohort. By age 2 years, 29% of Tennessee and New York children born in 2000–2001 had developed frequent otitis media, and 6% of each of these birth cohorts had pressure-equalizing tubes inserted. Comparing the 2000–2001 birth cohort to the 1998–1999 birth cohort, frequent otitis media declined by 17% and 28%, and pressure-equalizing tube insertions declined by 16% and 23% for Tennessee and New York children, respectively. For the 2000–2001 to the 2001–2002 birth cohort, frequent otitis media and pressure-equalizing tubes remained stable in New York but increased in Tennessee.

CONCLUSIONS. After heptavalent pneumococcal conjugate vaccine introduction, children were less likely to develop frequent otitis media or have pressure-equalizing tube insertions.
Improving Informed Consent: Suggestions From Parents of Children With Leukemia
Authors: Eder Michelle L. , Yamokoski Amy D. , Wittmann Peter W. , Kodish Eric D.
Published: April 2007

OBJECTIVE. The objective of this study was to report suggestions for improving the informed consent process from the perspective of parents of children with leukemia.

METHODS. Recommendations for improving informed consent were elicited from 140 parents of children who had been offered participation in a randomized clinical trial for the treatment of their acute leukemia. Four different methods and data collection time points were used with this group of parents, including open-ended, in-person interviews within 72 hours after the informed consent conference; follow-up telephone interviews 6 months after diagnosis; focus groups during year 3 of the project; and a parent advisory group on informed consent meeting in year 4.

RESULTS. The most frequently cited suggestions for improving informed consent during the interviews and focus groups related to giving parents more time to make their decision, the amount and type of information provided, organization of the consent conference, communication style, and providing additional materials. During the parent advisory group on informed consent meeting, parents developed specific guidelines for organization of the information that is presented during the consent process that include 7 major components: timing, sequence, checklist, checking for understanding, anticipatory guidance, segue into randomized clinical trial discussion with historical perspective, and choice.

CONCLUSIONS. Through the incorporation of parental perspectives that provide an authentic stakeholder voice, our research represents a true partnership approach to improving the consent process. Parents provided practical advice for improving informed consent that can be applied to most adult and pediatric patient populations.
Results of Random Drug Testing in an Adolescent Substance Abuse Program
Authors: Levy Sharon , Sherritt Lon , Vaughan Brigid L. , Germak Matthew , Knight John R.
Published: April 2007

OBJECTIVE. The objective of this study was to estimate from a random urine drug-testing program for adolescents the proportion of drug tests that are susceptible to interpretation errors.

METHODS. This was a secondary analysis of a clinical database and chart review from an adolescent outpatient substance abuse program at a large children's hospital. We analyzed from 110 adolescent patients (13–21 years of age) all 710 urine drug test results that were collected between December 2002 and July 2005 and 85 original laboratory reports for tests that were collected between December 2002 and May 2006 and were confirmed positive for opioids. We calculated the percentage of tests that were too dilute to interpret (potential false-negatives) and the percentage of confirmed positive tests for oxycodone that did not result in a positive initial screen (potential false-negatives). We also reviewed clinical information to determine whether confirmed positive tests resulted from legitimate use of prescription or over-the-counter medication (potential false-positives).

RESULTS. Of 710 drug tests, 40 negative tests were too dilute to interpret properly, and 45 of 217 positive tests resulted from prescription medication use for a total of 85 tests that were susceptible to error. Of the 85 confirmatory laboratory reports reviewed, 43 were positive for oxycodone, but only 16 of these had produced a positive opiate screen.

CONCLUSIONS. Unless proper procedures are used in collecting, analyzing, and interpreting laboratory testing for drugs, there is a substantial risk for error.
Parental Knowledge About Antibiotic Use: Results of a Cluster-Randomized, Multicommunity Intervention
Authors: Huang Susan S. , Rifas-Shiman Sheryl L. , Kleinman Ken , Kotch Jamie , Schiff Nancy , Stille Christopher J. , Steingard Ron , Finkelstein Jonathan A.
Published: April 2007

OBJECTIVE. The goal was to determine the impact of a community-wide educational intervention on parental misconceptions likely contributing to pediatric antibiotic overprescribing.

METHODS. We conducted a cluster-randomized trial of a 3-year, community-wide, educational intervention directed at parents of children <6 years of age in 16 Massachusetts communities to improve parental antibiotic knowledge and attitudes and to decrease unnecessary prescribing. Parents in 8 intervention communities were mailed educational newsletters and exposed to educational materials during visits to local pediatric providers, pharmacies, and child care centers. We compared responses from mailed surveys in 2000 (before the intervention) and 2003 (after the intervention) for parents in intervention and control communities. Analyses were performed on the individual level, clustered according to community.

RESULTS. There were 1106 (46%) and 2071 (40%) respondents to the 2000 and 2003 surveys, respectively. Between 2000 and 2003, the proportion of parents who answered ≥7 of 10 knowledge questions correctly increased significantly in both intervention (from 52% to 64%) and control (from 54% to 61%) communities. We did not detect a significant intervention impact on knowledge regarding appropriate antibiotic use in the population overall. In a subanalysis, we did observe a significant intervention effect among parents of Medicaid-insured children, who began with lower baseline knowledge scores.

CONCLUSIONS. Although knowledge regarding appropriate use of antibiotics is improving without additional targeted intervention among more socially advantaged populations, parents of Medicaid-insured children may benefit from educational interventions to promote judicious antibiotic use. These findings may have implications for other health education campaigns.
Antifungal Therapy in Children With Invasive Fungal Infections: A Systematic Review
Authors: Blyth Christopher C. , Palasanthiran Pamela , O'Brien Tracey A.
Published: April 2007

Invasive fungal infections are associated with significant morbidity and mortality. Differences between children and adults are reported, yet few trials of antifungal agents have been performed in pediatric populations. We performed a systematic review of the literature to guide appropriate pediatric treatment recommendations. From available trials that compared antifungal agents in either prolonged febrile neutropenia or invasive candidal or Aspergillus infection, no clear difference in treatment efficacy was demonstrated, although few trials were adequately powered. Differing antifungal pharmacokinetics between children and adults were demonstrated, requiring dose modification. Significant differences in toxicity, particularly nephrotoxicity, were identified between classes of antifungal agents. Therapy needs to be guided by the pathogen or suspected pathogens, the degree of immunosuppression, comorbidities (particularly renal dysfunction), concurrent nephrotoxins, and the expected length of therapy.
Paracetamol (Acetaminophen) Penetrates Readily Into the Cerebrospinal Fluid of Children After Intravenous Administration
Authors: Kumpulainen Elina , Kokki Hannu , Halonen Toivo , Heikkinen Marja , Savolainen Jouko , Laisalmi Merja
Published: April 2007

INTRODUCTION. The main action of paracetamol (acetaminophen) is presumed to be in the central nervous system. The central nervous system penetration of paracetamol has been described in children with intracranial pathologies but not in children with an intact blood-brain barrier.

OBJECTIVE. We investigated the cerebrospinal fluid penetration of paracetamol in 32 healthy children, aged 3 months to 12 years, who were undergoing surgery in the lower body using spinal anesthesia.

MATERIALS AND METHODS. In this open-label prospective study, children were given a single intravenous injection of paracetamol (15 mg/kg). Cerebrospinal fluid and venous blood samples were obtained between 5 minutes and 5 hours after injection. Paracetamol concentrations were determined from the cerebrospinal fluid and plasma by using a fluorescence polarization immunoassay.

RESULTS. Paracetamol was detected in cerebrospinal fluid from the earliest sample at 5 minutes, although in this sample paracetamol concentration was below the limit of quantification of 1.0 mg/L. Subsequent paracetamol concentrations in cerebrospinal fluid ranged between 1.3 and 18 mg/L (median: 7.2 mg/L), plasma concentrations ranged between 2.4 and 33 mg/L, and cerebrospinal fluid/plasma ratios ranged between 0.06 and 2.0. The highest CSF paracetamol concentration was detected at 57 minutes.

CONCLUSIONS. Paracetamol permeates readily into the cerebrospinal fluid of children. This fast and extensive transfer enables the rapid central analgesic and antipyretic action of intravenous paracetamol.
Pediatrics on the Web: 10 Years of Innovation and Discovery
Authors: Clarke Michael T.
Published: April 2007

The electronic edition of Pediatrics celebrates its 10th birthday this year. This article describes the origins and evolution of the online edition of Pediatrics, which, after launching in 1997, featured the world's first online-only section of a medical journal. Over the proceeding 10 years the journal introduced numerous innovations, including e-mail alerts, postpublication peer review, video supplements, online classified advertisements, Web-based manuscript submission, early release, and the development of the eJournal Archive. This article also describes the use and reception of the electronic journal. Whether measured by article accesses, citation rates, or the number of manuscript submissions, the electronic edition of Pediatrics has proven to be a success. It has allowed the journal to publish a larger number of articles and reach a wider audience than would have been economically possible with a print-only publication. Yet, even as Pediatrics recreates itself online, it is clear that there is much more that can be done to fully realize the potential of the new medium to facilitate professional communication.
Enhancing the Diversity of the Pediatrician Workforce
Authors:   Committee on Pediatric Workforce
Published: April 2007

This policy statement describes the key issues related to diversity within the pediatrician and health care workforce to identify barriers to enhancing diversity and offer policy recommendations to overcome these barriers in the future. The statement addresses topics such as health disparities, affirmative action, recent policy developments and reports on workforce diversity, and research on patient and provider diversity. It also broadens the discussion of diversity beyond the traditional realms of race and ethnicity to include cultural attributes that may have an effect on the quality of health care. Although workforce diversity is related to the provision of culturally effective pediatric care, it is a discrete issue that merits separate discussion and policy formulation. At the heart of this policy-driven action are multiorganizational and multispecialty collaborations designed to address substantive educational, financial, organizational, and other barriers to improved workforce diversity.
Quality of maize ( Zea mays L.) kernels as affected by the NP supplies of the soil
Authors: Izsáki Z.
Published: April 2007

In a long-term mineral fertilisation experiment with 64 treatments representing all possible combinations of four rates each of N, P and K, set up on chernozem meadow soil in Szarvas in 1989, the protein and oil contents and the amino acid and fatty acid compositions of the maize grain yield were analysed between 1997 and 2004.The protein content of the maize kernels increased by 1.1–1.5 percentage points up to a NO
3
-N level of 80–100 kg ha
−1
in the 0–60 cm soil layer prior to sowing. The year had a greater influence on the protein content than the N supplies. No consistent effect of N on the amino acid composition, detectable as a change in the ratio of any amino acid in the majority of experimental years, was observed. In the AL-P
2
O
5
range of 120–362 mg kg
−1
in the ploughed layer, the soil P supplies had no statistically significant effect on the kernel protein content. In most years the P supplies had little effect on the amino acid composition of the protein. The oil content and fatty acid composition of maize kernels was extremely stable, and was very little affected by the nutrient supplies or the year. During the experimental period excessive N supplies were only found to reduce the oil content and modify the fatty acid composition on one occasion. The oil content and fatty acid composition were not substantially affected by the P supplies.
Effect of increased UV-B radiation on the anthocyanin content of maize ( Zea mays L.) leaves
Authors: Pintér J. , Kósa E. , Hadi G. , Hegyi Z. , Spitkó T. , Tóth Z. , Szigeti Z. , Páldi E. , Marton L.
Published: April 2007

The level of UV-B radiation reaching the surface of the earth is increasing due to the thinning of the ozone layer in the stratosphere over recent decades. This has numerous negative effects on living organisms.Some of the Hungarian inbred maize lines examined under the climatic conditions in Chile exhibited an unusually high proportion of pollen mortality, flowering asynchrony and barrenness. The evidence suggests that this can be attributed to the approx. 30% greater UV-B radiation in Chile.The investigation of this problem within the framework of abiotic stress breeding programmes is extremely important in the light of the global rise in UV-B radiation, which may make it necessary to elaborate a selection programme to develop inbred lines with better tolerance of this type of radiation.In the course of the experiment the same ten inbred lines, having different maturity dates and genetic backgrounds, were tested for five years in Chile and Hungary. The tests focussed on anthocyanin, a flavonoid derivative involved in the absorption of damaging UV-B radiation.Averaged over years and varieties, the total anthocyanin content in the leaf samples was significantly higher in Chile than in Hungary. This was presumably a response at the metabolic level to the negative stress represented by higher UV-B radiation.In the five early-maturing flint lines the anthocyanin contents were more than 45% greater than those recorded in Hungary. This suggests that these genotypes, originating from northern regions, were not sufficiently adapted to the higher radiation level. In these samples higher UV-B caused a sharp rise in the quantity of anthocyanin, which absorbs the dangerous radiation. In late-maturing genotypes the initial content of the protective compound anthocyanin was higher at both locations, so in these types the high radiation level was not a problem and did not cause any substantial change.Similar conclusions were drawn from the results of fluorescence imaging. The F440/F690 ratio indicative of the stress level was higher in late lines with a high anthocyanin content, good tolerance and good adaptability.