bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombomodulin Ala455Val Polymorphism and the risk of cerebral infarction in a biracial population: the Stroke Prevention in Young Women Study
Authors: Cole John W , Roberts Stacy C , Gallagher Margaret , Giles Wayne H , Mitchell Braxton D , Steinberg Karen K , Wozniak Marcella A , Macko Richard F , Reinhart Laurie J , Kittner Steven J 
Published: January 2005

Abstract
Background
The genes encoding proteins in the thrombomodulin-protein C pathway are promising candidate genes for stroke susceptibility because of their importance in thrombosis regulation and inflammatory response. Several published studies have shown that the Ala455Val thrombomodulin polymorphism is associated with ischemic heart disease, but none has examined the association with stroke. Using data from the Stroke Prevention in Young Women Study, we sought to determine the association between the Ala455Val thrombomodulin polymorphism and the occurrence of ischemic stroke in young women.

Methods
All 59 hospitals in the greater Baltimore-Washington area participated in a population-based case-control study of stroke in young women. We compared 141 cases of first ischemic stroke (44% black) among women 15 to 44 years of age with 210 control subjects (35% black) who were identified by random digit dialing and frequency matched to the cases by age and geographical region of residence. Data on historical risk factors were collected by standardized interview. Genotyping of the thrombomodulin Ala455Val polymorphism was performed by pyrosequencing.

Results
The A allele (frequency = 0.85) was associated with stroke under the recessive model. After adjustment for age, race, cigarette smoking, hypertension, and diabetes, the AA genotype, compared with the AV and VV genotypes combined, was significantly associated with stroke (odds ratio 1.9, 95% CI 1.1–3.3). The AA genotype was more common among black than white control subjects (81% versus 68%) but there was no significant interaction between the risk genotype and race (adjusted odds ratio 2.7 for blacks and 1.6 for whites). A secondary analysis removing all probable (n = 16) and possible (n = 15) cardioembolic strokes demonstrated an increased association (odds ratio 2.2, 95% CI 1.2–4.2).

Conclusions
Among women aged 15 to 44 years, the AA genotype is more prevalent among blacks than whites and is associated with increased risk of early onset ischemic stroke. Removing strokes potentially related to cardioembolic phenomena increased this association. Further studies are needed to determine whether this polymorphism is functionally related to thrombomodulin expression or whether the association is due to population stratification or linkage to a nearby functional polymorphism.
Morphological brain differences between adult stutterers and non-stutterers
Authors: Jäncke Lutz , Hänggi Jürgen , Steinmetz Helmuth 
Published: January 2005

Abstract
Background
The neurophysiological and neuroanatomical foundations of persistent developmental stuttering (PDS) are still a matter of dispute. A main argument is that stutterers show atypical anatomical asymmetries of speech-relevant brain areas, which possibly affect speech fluency. The major aim of this study was to determine whether adults with PDS have anomalous anatomy in cortical speech-language areas.

Methods
Adults with PDS (n = 10) and controls (n = 10) matched for age, sex, hand preference, and education were studied using high-resolution MRI scans. Using a new variant of the voxel-based morphometry technique (augmented VBM) the brains of stutterers and non-stutterers were compared with respect to white matter (WM) and grey matter (GM) differences.

Results
We found increased WM volumes in a right-hemispheric network comprising the superior temporal gyrus (including the planum temporale), the inferior frontal gyrus (including the pars triangularis), the precentral gyrus in the vicinity of the face and mouth representation, and the anterior middle frontal gyrus. In addition, we detected a leftward WM asymmetry in the auditory cortex in non-stutterers, while stutterers showed symmetric WM volumes.

Conclusions
These results provide strong evidence that adults with PDS have anomalous anatomy not only in perisylvian speech and language areas but also in prefrontal and sensorimotor areas. Whether this atypical asymmetry of WM is the cause or the consequence of stuttering is still an unanswered question.
Successful obstetrical management of 110-day intertwin delivery interval without cerclage: counseling and conservative management approach to extreme asynchronous twin birth
Authors: Ghulmiyyah Labib M , Wehbe Salim A , Schwartz Seth A , Sills Eric Scott 
Published: January 2005

Abstract
Background
This report describes a patient counseling approach and non-surgical management of a dichorionic-diamniotic twin pregnancy where delivery of the second twin followed the delivery of the first by 110 days.

Case presentation
An early transvaginal sonogram at 19 1/2 weeks suggested cervical dilation with protruding amniotic membranes. Tocolytic and antibiotic therapy was initiated; no cerclage was placed. Spontaneous rupture of membranes and cord prolapse occurred 48 h later, resulting in delivery of a stillborn female infant. Conservative management was offered after counseling for possible risks associated with maternal sepsis, need for extended hospitalization, potential for hysterectomy and death. The cervix appeared closed after delivery and the umbilical cord was ligated, with subsequent spontaneous cord retraction in utero. Reassuring fetal status was observed for twin B without evidence of contractions or chorioamnionitis. A viable male infant (2894 g) was delivered vaginally at 35 1/2 weeks.

Conclusions
This report outlines a counseling approach useful for patients with premature delivery of one twin, and presents application of conservative obstetrical management principles for the aftercoming twin even when delivery interval is extreme.
Protocol for a randomised controlled trial of a decision aid for the management of pain in labour and childbirth [ISRCTN52287533]
Authors: Roberts Christine L , Raynes-Greenow Camille H , Nassar Natasha , Trevena Lyndal , McCaffery Kirsten 
Published: January 2005

Abstract
Background
Women report fear of pain in childbirth and often lack complete information on analgesic options prior to labour. Preferences for pain relief should be discussed before labour begins. A woman's antepartum decision to use pain relief is likely influenced by her cultural background, friends, family, the media, literature and her antenatal caregivers. Pregnant women report that information about analgesia was most commonly derived from hearsay and least commonly from health professionals. Decision aids are emerging as a promising tool to assist practitioners and their patients in evidence-based decision making.
Decision aids are designed to assist patients and their doctors in making informed decisions using information that is unbiased and based on high quality research evidence. Decision aids are non-directive in the sense that they do not aim to steer the user towards any one option, but rather to support decision making which is informed and consistent with personal values.

Methods/design
We aim to evaluate the effectiveness of a Pain Relief for Labour decision aid, with and without an audio-component, compared to a pamphlet in a three-arm randomised controlled trial. Approximately 600 women expecting their first baby and planning a vaginal birth will be recruited for the trial.
The primary outcomes of the study are decisional conflict (uncertainty about a course of action), knowledge, anxiety and satisfaction with decision-making and will be assessed using self-administered questionnaires. The decision aid is not intended to influence the type of analgesia used during labour, however we will monitor health service utilisation rates and maternal and perinatal outcomes. This study is funded by a competitive peer-reviewed grant from the Australian National Health and Medical Research Council (No. 253635).

Discussion
The Pain Relief for Labour decision aid was developed using the Ottawa Decision Support Framework and systematic reviews of the evidence about the benefits and risks of the non-pharmacological and pharmacological methods of pain relief for labour. It comprises a workbook and worksheet and has been developed in two forms – with and without an audio-component (compact disc). The format allows women to take the decision aid home and discuss it with their partner.
The DiAMOND trial protocol: a randomised controlled trial of two decision aids for mode of delivery among women with a previous caesarean section [ISRCTN84367722]
Authors: Montgomery Alan A ,   the DiAMOND Study Group
Published: January 2005

Abstract
Background
Caesarean section (CS) has become an increasingly common method of delivery worldwide, rising in the UK from 9% of deliveries in 1980 to over 21% 2001. This increase, and the question of whether CS should be available to women on request, has been the subject of considerable debate, and national reports and guidelines have specifically highlighted the importance of patient choice in the decision making process. For women who have already experienced CS, the UK National Institute of Clinical Excellence recommends that the decision should consider maternal preferences and priorities in addition to general discussion of the overall risks and benefits of CS. Decision aids for many different medical treatment and screening decisions have been developed and evaluated, but there is relatively little evidence for the use of decision aids for choice of mode of delivery among women with a previous CS. The aim of the study is to evaluate two interventions to assist decision making about mode of delivery among pregnant women with one previous CS.

Methods/design
Women with one previous CS are recruited to the trial during their booking visit at approximately 12–20 weeks' gestation in participating maternity units in Bristol, Weston and Dundee. Using central randomisation, women are allocated to one of three arms: information programme and website; decision analysis; usual care. Both interventions are computer-based, and are designed to provide women with detailed information about the potential outcomes for both mother and baby of planned vaginal delivery, planned CS and emergency CS. The decision analysis intervention additionally provides a recommended 'preferred option' based on maximised expected utility. There are two primary outcomes (decisional conflict and actual mode of delivery), and five secondary outcomes (anxiety, knowledge, perceptions of shared decision making; satisfaction with decision making process, proportion of women attempting vaginal delivery). Primary follow up for the questionnaire measures is at 36–37 weeks' gestation, and a total of 660 women will be recruited to the study. The primary intention-to-treat analyses will comprise three pair-wise comparisons between decision analysis, information and usual care groups, for each of the two primary outcomes. A qualitative study will investigate women's experiences of the decision making in more depth, and an economic evaluation from the perspective of the NHS will be conducted.

Discussion
Provision of information to women facing this decision appears variable. The DiAMOND study aims to inform best practice in this area by evaluating the effectiveness of two interventions designed to aid decision making.
The in vitroeffect of gefitinib ('Iressa') alone and in combination with cytotoxic chemotherapy on human solid tumours
Authors: Knight Louise A , Di Nicolantonio Federica , Whitehouse Pauline , Mercer Stuart , Sharma Sanjay , Glaysher Sharon , Johnson Penny , Cree Ian A 
Published: January 2005

Abstract
Background
Activation of the epidermal growth factor receptor (EGFR) triggers downstream signaling pathways that regulate many cellular processes involved in tumour survival and growth. Gefitinib ('Iressa') is an orally active tyrosine kinase inhibitor (TKI) targeted to the ATP-binding domain of EGFR (HER1; erbB1).

Methods
In this study we have used a standardised ATP-based tumour chemosensitivity assay (ATP-TCA) to measure the activity of gefitinib alone or in combination with different cytotoxic drugs (cisplatin, gemcitabine, oxaliplatin and treosulfan) against a variety of solid tumours (n = 86), including breast, colorectal, oesophageal and ovarian cancer, carcinoma of unknown primary site, cutaneous and uveal melanoma, non-small cell lung cancer (NSCLC) and sarcoma. The IC50 and IC90 were calculated for each single agent or combination. To allow comparison between samples the IndexSUM was calculated based on the percentage tumour growth inhibition (TGI) at each test drug concentration (TDC). Gefitinib was tested at concentrations ranging from 0.0625–2 microM (TDC = 0.446 microg/ml). This study represents the first use of a TKI in the assay.

Results
There was heterogeneity in the degree of TGI observed when tumours were tested against single agent gefitinib. 7% (6/86) of tumours exhibited considerable inhibition, but most showed a more modest response resulting in a low TGI. The median IC50 value for single agent gefitinib in all tumours tested was 3.98 microM. Interestingly, gefitinib had both positive and negative effects when used in combination with different cytotoxics. In 59% (45/76) of tumours tested, the addition of gefitinib appeared to potentiate the effect of the cytotoxic agent or combination (of these, 11% (5/45) had a >50% decrease in their IndexSUM). In 38% of tumours (29/76), the TGI was decreased when the combination of gefitinib + cytotoxic was used in comparison to the cytotoxic alone. In the remaining 3% (2/76) there was no change observed.

Conclusion
The in vitro model suggests that gefitinib may have differential effects in response to concomitant cytotoxic chemotherapy with the agents tested during this study. The mechanism involved may relate to the effect of TKIs on growth rate versus their effect on the ability of the cell to survive the stimulus to apoptosis produced by chemotherapy.
SMAC is expressed de novoin a subset of cervical cancer tumors
Authors: Espinosa Magali , Cantu David , Lopez Carlos M , De la Garza Jaime G , Maldonado Vilma A , Melendez-Zajgla Jorge 
Published: January 2005

Abstract
Background
Smac/Diablo is a recently identified protein that is released from mitochondria after apoptotic stimuli. It binds IAPs, allowing caspase activation and cell death. In view of its activity it might participate in carcinogenesis. In the present study, we analyzed Smac expression in a panel of cervical cancer patients.

Methods
We performed semi quantitative RT-PCR on 41 cervical tumor and 6 normal tissue samples. The study included 8 stage I cases; 16 stage II; 17 stage III; and a control group of 6 samples of normal cervical squamous epithelial tissue.

Results
Smac mRNA expression was below the detection limit in the normal cervical tissue samples. In contrast, 13 (31.7%) of the 41 cervical cancer biopsies showed detectable levels of this transcript. The samples expressing Smac were distributed equally among the stages (5 in stage I, 4 in stage II and 4 in stage III) with similar expression levels. We found no correlation between the presence of Smac mRNA and histology, menopause, WHO stage or disease status.

Conclusions
Smac is expressed de novo in a subset of cervical cancer patients, reflecting a possible heterogeneity in the pathways leading to cervical cancer. There was no correlation with any clinical variable.
BAG-1 haplo-insufficiency impairs lung tumorigenesis
Authors: Götz Rudolf , Kramer Boris W , Camarero Guadalupe , Rapp Ulf R 
Published: January 2005

Abstract
Background
BAG-1 is a multifunctional co-chaperone of heat shock proteins (Hsc70/Hsp70) that is expressed in most cells. It interacts with Bcl-2 and Raf indicating that it might connect protein folding with other signaling pathways. Evidence that BAG-1 expression is frequently altered in human cancers, in particular in breast cancer, relative to normal cells has been put forward but the notion that overexpression of BAG-1 contributes to poor prognosis in tumorigenesis remains controversial.

Methods
We have evaluated the effect of BAG-1 heterozygosity in mice in a model of non-small-cell lung tumorigenesis with histological and molecular methods. We have generated mice heterozygous for BAG-1, carrying a BAG-1 null allele, that in addition express oncogenic, constitutively active C-Raf kinase (SP-C C-Raf BxB) in type II pneumocytes. SP-C C-Raf BxB mice develop multifocal adenomas early in adulthood.

Results
We show that BAG-1 heterozygosity in mice impairs C-Raf oncogene-induced lung adenoma growth. Lung tumor initiation was reduced by half in BAG-1 heterozygous SP-C C-Raf BxB mice compared to their littermates. Tumor area was reduced by 75% in 4 month lungs of BAG-1 haploinsufficient mice compared to mice with two BAG-1 copies. Whereas BAG-1 heterozygosity did not affect the rate of cell proliferation or signaling through the mitogenic cascade in adenoma cells, it increased the rate of apoptosis.

Conclusion
Reduced BAG-1 expression specifically targets tumor cells to apoptosis and impairs tumorigenesis. Our data implicate BAG-1 as a key player in oncogenic transformation by Raf and identify it as a potential molecular target for cancer treatment.
Atypical presentation of hepatocellular carcinoma: a mass on the left thoracic wall
Authors: Çoban Şahin , Yüksel Osman , Köklü Seyfettin , Ceyhan Koray , Baykara Meltem , Dökmeci Abdulkadir 
Published: January 2005

Abstract
Background
Hepatocellular carcinoma is a common malignancy for which chronic hepatitis B infection has been defined as the most common etiologic factor. The most frequent metastatic sites are the lung, bone, lymphatics, and brain, respectively. Metastases to the chest wall have been reported only rarely.

Case presentation
We report a patient with hepatocellular carcinoma who presented with an isolated metastatic mass on the left anterolateral chest wall in the axillary region.

Conclusions
Metastasis of HCC should be included in the differential diagnosis of rapidly growing lesions in unusual localizations, particularly in patients with chronic liver disease even if a primary tumor can not be radiologically identified.
Penile metastasis from primary transitional cell carcinoma of the renal pelvis: first manifestation of systemic spread
Authors: Pomara Giorgio , Pastina Ilaria , Simone Maurizio , Casale Paolo , Marchetti Gabriella , Francesca Francesco 
Published: January 2005

Abstract
Background
Almost one-third of all penile metastases are detected at the same time as a primary tumor, whereas the remaining two-thirds are detected a mean of 18 months after the discovery of the primary tumor. Cutaneous metastasis of transitional cell carcinoma (TCC) is extremely rare and generally accepted as the late manifestation of a systemic spread.

Case presentation
We report the first case of simultaneous penile and lung metastases from a primary TCC of the renal pelvis in a 76-year-old man, that occurred 8 years after a left nephroureterectomy.

Conclusions
This case report underscores the importance of physical examinations of the skin of patients who undergo surgical procedures for TCC from bladder as well as from the upper urinary tract, including those seemingly without metastatic disease, because of the possibility of skin and penile metastatic spread.
Expression of inwardly rectifying potassium channels (GIRKs) and beta-adrenergic regulation of breast cancer cell lines
Authors: Plummer Howard K , Yu Qiang , Cakir Yavuz , Schuller Hildegard M 
Published: January 2005

Abstract
Background
Previous research has indicated that at various organ sites there is a subset of adenocarcinomas that is regulated by beta-adrenergic and arachidonic acid-mediated signal transduction pathways. We wished to determine if this regulation exists in breast adenocarcinomas. Expression of mRNA that encodes a G-protein coupled inwardly rectifying potassium channel (GIRK1) has been shown in tissue samples from approximately 40% of primary human breast cancers. Previously, GIRK channels have been associated with beta-adrenergic signaling.

Methods
Breast cancer cell lines were screened for GIRK channels by RT-PCR. Cell cultures of breast cancer cells were treated with beta-adrenergic agonists and antagonists, and changes in gene expression were determined by both relative competitive and real time PCR. Potassium flux was determined by flow cytometry and cell signaling was determined by western blotting.

Results
Breast cancer cell lines MCF-7, MDA-MB-361 MDA-MB 453, and ZR-75-1 expressed mRNA for the GIRK1 channel, while MDA-MB-468 and MDA-MB-435S did not. GIRK4 was expressed in all six breast cancer cell lines, and GIRK2 was expressed in all but ZR-75-1 and MDA-MB-435. Exposure of MDA-MB-453 cells for 6 days to the beta-blocker propranolol (1 μM) increased the GIRK1 mRNA levels and decreased beta2-adrenergic mRNA levels, while treatment for 30 minutes daily for 7 days had no effect. Exposure to a beta-adrenergic agonist and antagonist for 24 hours had no effect on gene expression. The beta adrenergic agonist, formoterol hemifumarate, led to increases in K+ flux into MDA-MB-453 cells, and this increase was inhibited by the GIRK channel inhibitor clozapine. The tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a high affinity agonist for beta-adrenergic receptors stimulated activation of Erk 1/2 in MDA-MB-453 cells.

Conclusions
Our data suggests β-adrenergic receptors and GIRK channels may play a role in breast cancer.
An unusual pathological finding of chronic lymphocitic leukemia and adenocarcinoma of the prostate after transurethral resection for complete urinary retention: case report
Authors: Ballario Riccardo , Beltrami Paolo , Cavalleri Stefano , Ruggera Lorenzo , Zorzi Maria Grazia , Artibani Walter 
Published: January 2005

Abstract
Background
We describe a patient who underwent transurethral resection of the prostate for urinary obstructive symptoms and had histological findings of adenocarcinoma of the prostate with prostatic localization of chronic lymphocitic leukemia (CLL).The contemporary presence of CLL, adenocarcinoma of the prostate and residual prostatic gland after transurethral resection has never been reported before and the authors illustrate how they managed this unusual patient.

Case presentation
A 79-years-old white man, presented with acute urinary retention, had a peripheral blood count with an elevated lymphocytosis (21.250/mL) with a differential of 65.3% lymphocytes and the prostate-specific antigen (PSA) value was 3.38 ng/mL with a percent free PSA of 8.28%. The transrectal ultrasound (TRUS) indicated an isoechonic and homogenic enlarged prostate of 42 cm3 and the abdomen ultrasound found a modest splenomegaly and no peripheral lymphadenophaty. The patient underwent transurethral resection of the prostate and had a pathological finding of adenocarcinoma in the prostate with a Gleason Score 4 (2+2) of less than 5% of the material (clinical stage T1a), associated with a diffused infiltration of chronic lymphocitic leukemia elements.

Conclusions
The incidental finding of a prostatic localization of a low-grade non-Hodgkin's lymphoma does not modify eventually further treatments for neither prostate cancer nor lymphoma. The presence of a low-grade and low-stage lymphoma, confirmed by a hematological evaluation, and the simultaneous evidence of an adenocarcinoma after transurethral resection of the prostate for acute urinary retention do not require any immediate treatment due to its long-term survival rate and the follow-up remains based on periodical PSA evaluation and complete blood count.