bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional oscillation of canonical clock genes in mouse peripheral tissues
Authors: Yamamoto Takuro , Nakahata Yasukazu , Soma Haruhiko , Akashi Makoto , Mamine Takayoshi , Takumi Toru 
Published: October 2004

Abstract
Background
The circadian rhythm of about 24 hours is a fundamental physiological function observed in almost all organisms from prokaryotes to humans. Identification of clock genes has allowed us to study the molecular bases for circadian behaviors and temporal physiological processes such as hormonal secretion, and has prompted the idea that molecular clocks reside not only in a central pacemaker, the suprachiasmatic nuclei (SCN) of hypothalamus in mammals, but also in peripheral tissues, even in immortalized cells. Furthermore, previous molecular dissection revealed that the mechanism of circadian oscillation at a molecular level is based on transcriptional regulation of clock and clock-controlled genes.

Results
We systematically analyzed the mRNA expression of clock and clock-controlled genes in mouse peripheral tissues. Eight genes (mBmal1, mNpas2, mRev-erbα, mDbp, mRev-erbβ, mPer3, mPer1 and mPer2; given in the temporal order of the rhythm peak) showed robust circadian expressions of mRNAs in all tissues except testis, suggesting that these genes are core molecules of the molecular biological clock. The bioinformatics analysis revealed that these genes have one or a combination of 3 transcriptional elements (RORE, DBPE, and E-box), which are conserved among human, mouse, and rat genome sequences, and indicated that these 3 elements may be responsible for the biological timing of expression of canonical clock genes.

Conclusions
The observation of oscillatory profiles of canonical clock genes is not only useful for physiological and pathological examination of the circadian clock in various organs but also important for systematic understanding of transcriptional regulation on a genome-wide basis. Our finding of the oscillatory expression of canonical clock genes with a temporal order provides us an interesting hypothesis, that cyclic timing of all clock and clock-controlled genes may be dependent on several transcriptional elements including 3 known elements, E-box, RORE, and DBPE.
A report of dangerously high carbon monoxide levels within the passenger compartment of a snow-obstructed vehicle
Authors: Griffin Jill A , Playe Stephen J , Osborne Benjamin , Smithline Howard A 
Published: October 2004

Abstract
Background
We sought to determine how quickly carbon monoxide would accumulate in the passenger compartment of a snow-obstructed vehicle.

Methods
A 1992 sedan was buried in snow to the level of the undercarriage, the ignition was then engaged and carbon monoxide levels recorded at 2.5-minute intervals. The primary outcome was the time at which a lethal carbon monoxide level was detected. Six trials were conducted: windows closed; windows open one inch; windows open 6 inches; windows closed and tailpipe swept clear of snow; windows closed and one cubic foot of snow removed around tailpipe; windows closed and tailpipe completely cleared of snow to ground level in a path 12 inches wide.

Results
Lethal levels of carbon monoxide occurred within 2.5 minutes in the vehicle when the windows were closed, within 5 minutes when the widows were opened one inch, and within 7.5 minutes when the widows were opened six inches. Dangerously high levels of carbon monoxide were detected within the vehicle when the tailpipe had been swept clear of snow and when a one cubic foot area had been cleared around the tailpipe. When the tailpipe was completely unobstructed the carbon monoxide level was zero.

Conclusions
Lethal levels of carbon monoxide occurred within minutes in this snow-obstructed vehicle.
Lack of association between vascular dementia and Chlamydia pneumoniae infection: a case-control study
Authors: Chan Carusone Soo , Smieja Marek , Molloy William , Goldsmith Charlie H , Mahony Jim , Chernesky Max , Gnarpe Judy , Standish Tim , Smith Stephanie , Loeb Mark 
Published: October 2004

Abstract
Background
Chronic inflammation appears to play a role in the pathogenesis of vascular dementia. Given the association between Chlamydia pneumoniae and stroke, the possibility exists that previous exposure to C. pneumoniae may play a role in vascular dementia. The objective of this study was to determine if there was an association between serological evidence of C. pneumoniae infection or inflammatory markers with vascular dementia.

Methods
28 case-patients with vascular dementia at a geriatric clinic and 24 caregiver-controls were tested for C. pneumoniae IgG and IgA antibodies. The association between vascular dementia and C. pneumoniae titres as well as inflammatory markers was estimated by using both conditional logistic regression and stratified logistic regression.

Results
When matched cases were compared to controls, there was no significant difference in elevated C. pneumoniae specific IgG antibodies (titre ≥ 1:32), odds ratio [OR] 1.3 (95% confidence intervals [CI] 0.3 to 6.0), p = 0.71, or in elevated C. pneumoniae specific IgA antibodies (titre ≥ 1:16), OR 2.0 (95%CI 0.5 to 8.0), p = 0.33 indicative of past or persistent C. pneumoniae infection. Similarly, no difference in high IgG or IgA antibody levels (IgG titre ≥ 1:512 or IgA titre ≥ 1:64) between the two groups, indicative of recent C. pneumoniae infection, was found, OR 0.4 (95%CI 0.1 to 2.1), p = 0.27. For C-reactive protein (CRP), the mean difference between 18 matched pairs (case – control) was – 3.33 mg/L. There was no significant difference between cases and controls when comparing log transformed values, OR 0.03 (95%CI 0.00 to 2.89), p = 0.13 or comparing CRP values above or below the median, OR 0.8 (95%CI 0.2 to 3.4), p = 0.71. For fibrinogen, the mean difference between pairs (case – control) was -0.07 g/L. There was no statistical difference between cases and controls when comparing log transformed values, OR 0.6 (95%CI 0.0 to 31.2), p = 0.79 or between fibrinogen values above and below the median, OR = 0.5 (95%CI 0.1 to 2.0), p = 0.50.

Conclusion
We found no evidence for a significant association between C. pneumoniae infection, inflammatory markers such as CRP and fibrinogen, and vascular dementia.
Cerebral relapse of metastatic gastrointestinal stromal tumor during treatment with imatinib mesylate: Case report
Authors: Hughes Brett , Yip Desmond , Goldstein David , Waring Paul , Beshay Victoria , Chong Guan 
Published: October 2004

Abstract
Background
The management of unresectable or metastatic gastrointestinal stromal tumors (GISTs) has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are sanctuary sites such as the central nervous system where imatinib does not achieve adequate concentrations. We describe the case of a man with metastatic GIST who experienced multiple cerebral relapses of disease while systemic disease progression appeared to be controlled by imatinib.

Case presentation
A 47-year-old man presented in July 1999 with a jejunal GIST with multiple hepatic metastases. The jejunal primary was resected and after unsuccessful cytoreductive chemotherapy, the liver metastases were also resected in December 1999. The patient subsequently relapsed in August 2001 with symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular metastases all confirmed on CT and PET scanning. Biopsy confirmed recurrent GIST. MRI and lumbar puncture excluded central nervous system involvement. The patient was commenced on imatinib 400 mg bd in September 2001 through a clinical trial.
The symptoms improved with objective PET and CT scan response until December 2002 when the patient developed a right-sided foot drop. MRI scan showed a left parasagittal tumor which was resected and confirmed histologically to be metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol but recommenced in February 2003 on a compassionate use program. The left parasagittal metastasis recurred and required subsequent re-excision in September 2003 and January 2004. Control of the systemic GIST was temporarily lost on reduction of the dose of imatinib (due to limited drug supply) but on increasing the dose back to 800 mg per day, systemic disease was stabilized for a period of time before generalised progression occurred.

Conclusion
This case illustrates that the brain can be a sanctuary site to treatment of GISTs with imatinib. Maintaining dosing of imatinib in the face of isolated sites of disease progression is also important, as other metastatic sites may still be sensitive.
Surveillance of antimicrobial resistance at a tertiary hospital in Tanzania
Authors: Blomberg Bjørn , Mwakagile Davis SM , Urassa Willy K , Maselle Samwel Y , Mashurano Marcellina , Digranes Asbjørn , Harthug Stig , Langeland Nina 
Published: October 2004

Abstract
Background
Antimicrobial resistance is particularly harmful to infectious disease management in low-income countries since expensive second-line drugs are not readily available. The objective of this study was to implement and evaluate a computerized system for surveillance of antimicrobial resistance at a tertiary hospital in Tanzania.

Methods
A computerized surveillance system for antimicrobial susceptibility (WHONET) was implemented at the national referral hospital in Tanzania in 1998. The antimicrobial susceptibilities of all clinical bacterial isolates received during an 18 months' period were recorded and analyzed.

Results
The surveillance system was successfully implemented at the hospital. This activity increased the focus on antimicrobial resistance issues and on laboratory quality assurance issues. The study identified specific nosocomial problems in the hospital and led to the initiation of other prospective studies on prevalence and antimicrobial susceptibility of bacterial infections. Furthermore, the study provided useful data on antimicrobial patterns in bacterial isolates from the hospital. Gram-negative bacteria displayed high rates of resistance to common inexpensive antibiotics such as ampicillin, tetracycline and trimethoprim-sulfamethoxazole, leaving fluoroquinolones as the only reliable oral drugs against common Gram-negative bacilli. Gentamicin and third generation cephalosporins remain useful for parenteral therapy.

Conclusion
The surveillance system is a low-cost tool to generate valuable information on antimicrobial resistance, which can be used to prepare locally applicable recommendations on antimicrobial use. The system pinpoints relevant nosocomial problems and can be used to efficiently plan further research. The surveillance system also functions as a quality assurance tool, bringing attention to methodological issues in identification and susceptibility testing.
Description and evaluation of an EBM curriculum using a block rotation
Authors: Thom David H , Haugen Julie , Sommers Peter S , Lovett Peter 
Published: October 2004

Abstract
Background
While previous authors have emphasized the importance of integrating and reinforcing evidence-based medicine (EBM) skills in residency, there are few published examples of such curricula. We designed an EBM curriculum to train family practice interns in essential EBM skills for information mastery using clinical questions generated by the family practice inpatient service. We sought to evaluate the impact of this curriculum on interns, residents, and faculty.

Methods
Interns (n = 13) were asked to self-assess their level of confidence in basic EBM skills before and after their 2-week EBM rotation. Residents (n = 21) and faculty (n = 12) were asked to assess how often the answers provided by the EBM intern to the inpatient service changed medical care. In addition, residents were asked to report how often they used their EBM skills and how often EBM concepts and tools were used in teaching by senior residents and faculty. Faculty were asked if the EBM curriculum had increased their use of EBM in practice and in teaching.

Results
Interns significantly increased their confidence over the course of the rotation. Residents and faculty felt that the answers provided by the EBM intern provided useful information and led to changes in patient care. Faculty reported incorporating EBM into their teaching (92%) and practice (75%). Residents reported applying the EBM skills they learned to patient care (86%) and that these skills were reinforced in the teaching they received outside of the rotation (81%). All residents and 11 of 12 faculty felt that the EBM curriculum had improved patient care.

Conclusions
To our knowledge, this is the first published EBM curriculum using an individual block rotation format. As such, it may provide an alternative model for teaching and incorporating EBM into a residency program.
Intracardiac echocardiography to guide transseptal catheterization for radiofrequency catheter ablation of left-sided accessory pathways: two case reports
Authors: Citro Rodolfo , Ducceschi Valentino , Salustri Alessandro , Santoro Michele , Salierno Michele , Gregorio Giovanni 
Published: October 2004

AbstractIntracardiac echocardiography (ICE) is a useful tool for guiding transseptal puncture during electrophysiological mapping and ablation procedures. Left-sided accessory pathways (LSAP) can be ablated by using two different modalities: retrograde approach through the aortic valve and transseptal approach with puncture of the fossa ovalis. We shall report two cases of LSAP where transcatheter radiofrequency ablation (TCRFA) was firstly attempted via transaortic approach with ineffective results. Subsequently, a transseptal approach under ICE guidance has been performed. During atrial septal puncture ICE was able to locate the needle tip position precisely and provided a clear visualization of the "tenting effect" on the fossa ovalis. ICE allowed a better mapping of the mitral ring and a more effective catheter ablation manipulation and tip contact which resulted in a persistent and complete ablation of the accessory pathway with a shorter time of fluoroscopic exposure. ICE-guided transseptal approach might be a promising modality for TCRFA of LSAP.
Improved gene delivery to human saphenous vein cells and tissue using a peptide-modified adenoviral vector
Authors: Work Lorraine M , Reynolds Paul N , Baker Andrew H 
Published: October 2004

AbstractThe establishment of efficient gene delivery to target human tissue is a major obstacle for transition of gene therapy from the pre-clinical phases to the clinic. The poor long-term patency rates for coronary artery bypass grafting (CABG) is a major clinical problem that lacks an effective and proven pharmacological intervention. Late vein graft failure occurs due to neointima formation and accelerated atherosclerosis. Since CABG allows a clinical window of opportunity to genetically modify vein ex vivo prior to grafting it represents an ideal opportunity to develop gene-based therapies. Adenoviral vectors have been frequently used for gene delivery to vein ex vivo and pre-clinical studies have shown effective blockade in neointima development by overexpression of candidate therapeutic genes. However, high titers of adenovirus are required to achieve sufficient gene delivery to provide therapeutic benefit. Improvement in the uptake of adenovirus into the vessel wall would therefore be of benefit. Here we determined the ability of an adenovirus serotype 5 vector genetically-engineered with the RGD-4C integrin targeting peptide inserted into the HI loop (Ad-RGD) to improve the transduction of human saphenous vein smooth muscle cells (HSVSMC), endothelial cells (HSVEC) and intact saphenous vein compared to a non-modified virus (Ad-CTL). We exposed each cell type to virus for 10, 30 or 60 mins and measured transgene at 24 h post infection. For both HSVSMC and HSVEC Ad-RGD mediated increased transduction, with the largest increases observed in HSVSMC. When the experiments were repeated with intact human saphenous vein (the ultimate clinical target for gene therapy), again Ad-RGD mediated higher levels of transduction, at all clinically relevant exposures times (10, 30 and 60 mins tissue:virus exposure). Our study demonstrates the ability of peptide-modified Ad vectors to improve transduction to human vein graft cells and tissue and has important implications for gene therapy for CABG.
Multicenter Phase II Study of the Oral MEK Inhibitor, CI-1040, in Patients With Advanced Non-Small-Cell Lung, Breast, Colon, and Pancreatic Cancer
Authors: Rinehart John , Adjei Alex A. , LoRusso Patricia M. , Waterhouse David , Hecht J. Randolph , Natale Ronald B. , Hamid Oday , Varterasian Mary , Asbury Peggy , Kaldjian Eric P. , Gulyas Stephen , Mitchell David Y. , Herrera Roman , Sebolt-Leopold Judith S. , Meyer Mark B. 
Published: October 2004

Purpose This multicenter, open-label, phase II study was undertaken to assess the antitumor activity and safety of the oral mitogen-activated extracellular signal regulated kinase kinase (MEK) inhibitor, CI-1040, in breast cancer, colon cancer, non-small-cell lung cancer (NSCLC), and pancreatic cancer. Patients and Methods Patients with advanced colorectal, NSCLC, breast, or pancreatic cancer received oral CI-1040 continuously at 800 mg bid. All patients had measurable disease at baseline, a performance status of 2 or less, and adequate bone marrow, liver, and renal function. Expression of pERK, pAkt, and Ki-67 was assessed in archived tumor specimens by quantitative immunohistochemistry. Results Sixty-seven patients with breast (n = 14), colon (n = 20), NSCLC (n = 18), and pancreatic (n = 15) cancer received a total of 194 courses of treatment (median, 2.0 courses; range, one to 14 courses). No complete or partial responses were observed. Stable disease (SD) lasting a median of 4.4 months (range, 4 to 18 months) was confirmed in eight patients (one breast, two colon, two pancreas, and three NSCLC patients). Treatment was well tolerated, with 81% of patients experiencing toxicities of grade 2 or less severity. Most common toxicities included diarrhea, nausea, asthenia, and rash. A mild association (P < .055) between baseline pERK expression in archived tumor specimens and SD was observed. Conclusion CI-1040 was generally well tolerated but demonstrated insufficient antitumor activity to warrant further development in the four tumors tested. PD 0325901, a second generation MEK inhibitor, has recently entered clinical development and, with significantly improved pharmacologic and pharmaceutical properties compared with CI-1040, it may better test the therapeutic potential of MEK inhibition in cancer.
Prolonged Clinical and Molecular Remission in Patients With Low-Grade or Follicular Non-Hodgkin's Lymphoma Treated With Rituximab Plus CHOP Chemotherapy: 9-Year Follow-Up
Authors: Czuczman Myron S. , Weaver Robin , Alkuzweny Baha , Berlfein Judy , Grillo-López Antonio J. 
Published: October 2004

Purpose Long-term follow-up with updated time to disease progression (TTP) and duration of response (DR) data are presented from a multicenter, phase II trial of rituximab/cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) combination therapy in 40 patients with CD20+, B-cell, non-Hodgkin's lymphoma (NHL). Revised response rates based on International Workshop Response Criteria are also provided. Patients and Methods Enrollment began in April 1994 and consisted of patients with histologically confirmed, low-grade, B-cell lymphoma who had received no prior chemotherapy or who had no more than four prior standard therapies. Patients received six cycles of CHOP and six infusions of rituximab. Results Eight (21%) of the 38 treated patients were classified as International Working Formulation (IWF) A, 16 (42%) were IWF B, 13 (34%) were IWF C, and one (3%) was IWF D. Nine (24%) of 38 patients had received prior chemotherapy. Nine (24%) of 38 were considered poor risk according to the Follicular Lymphoma International Prognostic Index. Overall response rate was 100%; 87% of patients achieved a complete response or unconfirmed complete response. The median TTP and DR were 82.3 months and 83.5 months, respectively. Seven of eight patients who were bcl-2 positive at baseline converted to negative, and three of the seven patients have sustained the molecular remission. Conclusion Although a cure has not been found yet for follicular NHL, the R-CHOP combination provides a lengthy response duration in patients with relapsed or newly diagnosed indolent NHL.
Clinical Outcome of Lymphoma Patients After Idiotype Vaccination Is Correlated With Humoral Immune Response and Immunoglobulin G Fc Receptor Genotype
Authors: Weng Wen-Kai , Czerwinski Debra , Timmerman John , Hsu Frank J. , Levy Ronald 
Published: October 2004

PurposeThe unique immunoglobulin idiotype (Id) expressed by each B-cell lymphoma is a target for immunotherapy. Vaccination with Id induces humoral and/or cellular anti-Id immune responses. However, the clinical impact of these anti-Id immune responses is unknown. We and others have previously reported that immunoglobulin G Fc receptor (FcγR) polymorphisms predict the clinical response of lymphoma patients to passive anti-CD20 antibody infusions. In this study, we tested whether anti-Id immune responses or FcγR polymorphisms associate with clinical outcome of patients who received Id vaccination.Patients and MethodsWe analyzed 136 patients with follicular lymphoma who had received Id vaccination. The anti-Id immune responses were measured and FcγRIIIa and FcγRIIa polymorphisms were determined and correlated with clinical outcome for these patients.ResultsPatients who mounted humoral immune responses had a longer progression-free survival (PFS) than those who did not (8.21 v 3.38 years; P = .018). Patients with FcγRIIIa 158 valine/valine (V/V) genotype also had a longer PFS than those with valine/phenylalanine (V/F) or phenylalanine/phenylalanine (F/F) genotypes (V/V, 8.21 v V/F, 3.38 years; P = .004; v F/F, 4.47 years; P = .035). Multivariate analysis using the Cox proportional hazards model showed that V/V genotype and humoral immune responses were independent positive predictors for PFS.ConclusionThis study is the first to identify the predictive value of FcγR polymorphism on clinical outcome in patients who received active immunotherapy with tumor antigen vaccines. Our results imply that the antibodies induced against a tumor antigen are beneficial and that FcγR-bearing cells mediate an antitumor effect by killing antibody-coated tumor cells.