bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiepileptic drugs and bone metabolism
Authors: Valsamis Helen A , Arora Surender K , Labban Barbara , McFarlane Samy I 
Published: September 2006

Abstract
Anti-epileptic medications encompass a wide range of drugs including anticonvulsants, benzodiazepines, enzyme inducers or inhibitors, with a variety effects, including induction of cytochrome P450 and other enzyme, which may lead to catabolism of vitamin D and hypocalcemia and other effects that may significantly effect the risk for low bone mass and fractures. With the current estimates of 50 million people worldwide with epilepsy together with the rapid increase in utilization of these medications for other indications, bone disease associated with the use of anti-epileptic medications is emerging as a serious health threat for millions of people. Nevertheless, it usually goes unrecognized and untreated. In this review we discuss the pathophysiologic mechanisms of bone disease associated with anti-epileptic use, including effect of anti-epileptic agents on bone turnover and fracture risk, highlighting various strategies for prevention of bone loss and associated fractures a rapidly increasing vulnerable population.
Decreases in procalcitonin and C-reactive protein are strong predictors of survival in ventilator-associated pneumonia
Authors: Seligman Renato , Meisner Michael , Lisboa Thiago C , Hertz Felipe T , Filippin Tania B , Fachel Jandyra MG , Teixeira Paulo JZ 
Published: September 2006

Abstract
Introduction
This study sought to assess the prognostic value of the kinetics of procalcitonin (PCT), C-reactive protein (CRP) and clinical scores (clinical pulmonary infection score (CPIS), Sequential Organ Failure Assessment (SOFA)) in the outcome of ventilator-associated pneumonia (VAP) at an early time point, when adequacy of antimicrobial treatment is evaluated.

Methods
This prospective observational cohort study was conducted in a teaching hospital. The subjects were 75 patients consecutively admitted to the intensive care unit from October 2003 to August 2005 who developed VAP. Patients were followed for 28 days after the diagnosis, when they were considered survivors. Patients who died before the 28th day were non-survivors. There were no interventions.

Results
PCT, CRP and SOFA score were determined on day 0 and day 4. Variables included in the univariable logistic regression model for survival were age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, decreasing ΔSOFA, decreasing ΔPCT and decreasing ΔCRP. Survival was directly related to decreasing ΔPCT with odds ratio (OR) = 5.67 (95% confidence interval 1.78 to 18.03), decreasing ΔCRP with OR = 3.78 (1.24 to 11.50), decreasing ΔSOFA with OR = 3.08 (1.02 to 9.26) and APACHE II score with OR = 0.92 (0.86 to 0.99). In a multivariable logistic regression model for survival, only decreasing ΔPCT with OR = 4.43 (1.08 to 18.18) and decreasing ΔCRP with OR = 7.40 (1.58 to 34.73) remained significant. Decreasing ΔCPIS was not related to survival (p = 0.59). There was a trend to correlate adequacy to survival. Fifty percent of the 20 patients treated with inadequate antibiotics and 65.5% of the 55 patients on adequate antibiotics survived (p = 0.29).

Conclusion
Measurement of PCT and CRP at onset and on the fourth day of treatment can predict survival of VAP patients. A decrease in either one of these marker values predicts survival.
Biological markers of lung injury before and after the institution of positive pressure ventilation in patients with acute lung injury
Authors: Cepkova Magda , Brady Sandra , Sapru Anil , Matthay Michael A , Church Gwynne 
Published: September 2006

Abstract
Background
Several biological markers of lung injury are predictors of morbidity and mortality in patients with acute lung injury (ALI). The low tidal volume lung-protective ventilation strategy is associated with a significant decrease in plasma biomarker levels compared to the high tidal volume ventilation strategy. The primary objective of this study was to test whether the institution of lung-protective positive pressure ventilation in spontaneously ventilating patients with ALI exacerbates pre-existing lung injury by using measurements of biomarkers of lung injury before and after intubation.

Materials and methods
A prospective observational cohort study was conducted in the intensive care unit of a tertiary care university hospital. Twenty-five intubated, mechanically ventilated patients with ALI were enrolled. Physiologic data and serum samples were collected within 6 hours before intubation and at two different time points within the first 24 hours after intubation to measure the concentration of interleukin (IL)-6, IL-8, intercellular adhesion molecule 1 (ICAM-1), and von Willebrand factor (vWF). The differences in biomarker levels before and after intubation were analysed using repeated measures analysis of variance and a paired t test with correction for multiple comparisons.

Results
Before endotracheal intubation, all of the biological markers (IL-8, IL-6, ICAM-1, and vWF) were elevated in the spontaneously breathing patients with ALI. After intubation and the institution of positive pressure ventilation (tidal volume 7 to 8 ml/kg per ideal body weight), none of the biological markers was significantly increased at either an early (3 ± 2 hours) or later (21 ± 5 hours) time point. However, the levels of IL-8 were significantly decreased at the later time point (21 ± 5 hours) after intubation. During the 24-hour period after intubation, the PaO2/FiO2 (partial pressure of arterial oxygen/fraction of the inspired oxygen) ratio significantly increased and the plateau airway pressure significantly decreased.

Conclusion
Levels of IL-8, IL-6, vWF, and ICAM-1 are elevated in spontaneously ventilating patients with ALI prior to endotracheal intubation. The institution of a lung-protective ventilation strategy with positive pressure ventilation does not further increase the levels of biological markers of lung injury. The results suggest that the institution of a lung-protective positive pressure ventilation strategy does not worsen the pre-existing lung injury in most patients with ALI.
Control of NK cell functions by CD4+CD25+ regulatory T cells
Authors: Ralainirina Natacha , Poli Aurélie , Michel Tatiana , Poos Linda , Andrès Emmanuel , Hentges François , Zimmer Jacques 
Published: September 2006

AbstractRegulatory T cells (Treg) are key players in the maintenance of peripheral tolerance. As a result of suppressive effects on CD4+ and CD8+ effector T cells, Treg control the adaptive immune system and prevent autoimmunity. In addition, they inhibit B lymphocytes, dendritic cells, and monocytes/macrophages. It is interesting that several recent papers show that CD4+CD25+ Treg are also able to inhibit NK cells. Thus, Treg exert their control on immune responses from the onset (triggering of innate immune cells) to the effector phase of adaptive immunity (B and T cell-mediated responses). That Treg inhibit NK cells suggests that their uncontrolled activation might break self-tolerance and induce “innate” autoimmune pathology. Conversely, Treg-mediated suppression of NK cell functions might have negative effects, as these cells are important in defense against infections and cancer. It is conceivable that Treg might dampen efficient activation of NK cells in these diseases.
Pharmacodynamic Studies of Gefitinib in Tumor Biopsy Specimens From Patients With Advanced Gastric Carcinoma
Authors: Rojo Federico , Tabernero Josep , Albanell Joan , Van Cutsem Eric , Ohtsu Atsushi , Doi Toshihiko , Koizumi Wasaburo , Shirao Kuniaki , Takiuchi Hiroya , Cajal S. Ramon , Baselga José 
Published: September 2006

Purpose Epidermal growth factor receptor (EGFR) is highly expressed in some gastric cancers and is implicated in cancer cell growth and proliferation. The objective of this study was to assess the in situ biologic activity of the EGFR tyrosine kinase inhibitor gefitinib in gastric tumor samples in a phase II study. Methods Patients with previously treated stage IV adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to receive gefitinib (250 or 500 mg/d). Tumor biopsies, obtained at screening and on day 28 of treatment, were assessed for biomarker expression using immunohistochemistry and analysis of apoptosis. Results One hundred sixteen tumor samples from 70 patients were available, 70 were baseline and 46 were on-therapy biopsies. At baseline, levels of EGFR expression significantly correlated with levels of phosphorylated EGFR (pEGFR; P < .001) and Ki67 expression (P = .011), but not with phosphorylated mitogen-activated protein kinase (pMAPK). After gefitinib treatment, levels of pEGFR in tumor cells were significantly reduced (P = .001); this was not the case for pMAPK and phosphorylated Akt (pAkt). However, in some cases gefitinib inhibited pAkt and these tumors had enhanced apoptosis. Likewise, there was a significant correlation between increased exposure to geftinib and enhanced apoptosis. Conclusion Gefitinib reached the tumors at concentrations sufficient to inhibit EGFR activation in advanced gastric carcinoma patients, although this did not translate into clinical benefit. Overall, intratumoral phosphorylation of MAPK and Akt was not significantly inhibited by gefitinib. However, the finding that decreases in pAkt correlated with enhanced apoptosis deserves further exploration.
Prediction of Breast Tumor Progression by Integrity of Free Circulating DNA in Serum
Authors: Umetani Naoyuki , Giuliano Armando E. , Hiramatsu Suzanne H. , Amersi Farin , Nakagawa Taku , Martino Silvana , Hoon Dave S.B. 
Published: September 2006

Purpose Cell-free DNA circulating in serum is a candidate molecular biomarker for malignant tumors. Unlike uniformly truncated DNA released from apoptotic cells, DNA released from dead cancer cells varies in size. Serum DNA integrity, the ratio of longer fragments to total DNA, may be clinically useful for detecting breast cancer progression. Patients and Methods Serum samples from 51 healthy females and 83 females with primary breast cancers (eight American Joint Committee on Cancer stage 0, 24 stage I, 27 stage II, 21 stage III, and three stage IV) were assessed preoperatively. Serum DNA integrity was assessed by fragment length-dependent quantitative real-time polymerase chain reaction of ALU DNA repeats. Results Mean serum DNA integrity was significantly higher in patients with stage II, III, and IV breast cancers than in healthy females (P = .005, P < .0001, and P = .002, respectively). The receiver operating characteristic (ROC) curve for discriminating patients with stage II or more advanced breast cancers from healthy females had an area under the curve (AUC) of 0.79 (95% CI, 0.70 to 0.86). Mean serum DNA integrity was positively correlated to size of invasive cancers (r = 0.48; P < .0001) and significantly higher in the presence of lymphovascular invasion (LVI; 0.25 ± 0.02 v 0.17 ± 0.02; P < .0001) or lymph node (LN) metastasis (0.27 ± 0.02 v 0.14 ± 0.02; P < .0001). The ROC curve for discriminating LN metastasis had an AUC of 0.81 (95% CI, 0.72 to 0.89). Serum DNA integrity and LVI were significant for predicting LN metastasis in a multivariate analysis (P = .0002 and P < .0001, respectively). Conclusion Integrity of serum circulating DNA is a promising molecular biomarker for detecting breast cancer tumor progression and regional LN metastases.
High Expression of the ETS Transcription Factor ERG Predicts Adverse Outcome in Acute T-Lymphoblastic Leukemia in Adults
Authors: Baldus Claudia D. , Burmeister Thomas , Martus Peter , Schwartz Stefan , Gökbuget Nicola , Bloomfield Clara D. , Hoelzer Dieter , Thiel Eckhard , Hofmann Wolf K. 
Published: September 2006

Purpose In adult T-lymphoblastic leukemia (T-ALL) disease-free survival remains limited to 32% to 46%. The adverse prognosis in T-ALL has not been attributed to cytogenetic or molecular aberrations. We have determined the prognostic impact of the oncogenic transcription factor ERG in T-ALL. Patients and Methods ERG expression was analyzed by real-time polymerase chain reaction (PCR) in 105 adults with newly diagnosed T-ALL treated on the German ALL protocols. Patients were dichotomized at ERG′s median expression into low (n = 52) and high (n = 53) expressers. Homeobox (HOX) 11 and HOX11L2 expression was determined by real-time PCR. Results High ERG expressers compared with low ERG expressers had an inferior overall survival (OS, P = .02; 5-year OS: high ERG 26% v low ERG 58%) and relapse-free survival (RFS, P = .003; 5-year RFS: high ERG 34% v low ERG 72%). On multivariable analysis high ERG expression (P = .005), immunophenotypic subgroups (early v mature v thymic T-ALL; overall P = .04), HOX11L2 positivity (P = .055), and absence of HOX11 (P = .017) were independent adverse risk factors predicting RFS. Patients with high ERG expression had a hazard ratio (HR) for relapse of 3.2. Within the good prognostic subgroup of thymic T-ALL (n = 57), high ERG (HR, 4.1; P = .02) and presence of HOX11L2 (HR, 6.6; P = .008) were independent adverse factors for RFS. Conclusion High expression of ERG is an adverse risk factor in adult T-ALL. Within thymic T-ALL, otherwise classified as standard-risk, high ERG expression-identified patients that were four times more likely to fail long-term RFS. The prognostic impact of ERG may assist treatment stratification and suggest the need of alternative regimens.
Hyperinsulinemia, Impaired Glucose Tolerance, and Diabetes Mellitus in Survivors of Childhood Cancer: Prevalence and Risk Factors
Authors: Neville Kristen A. , Cohn Richard J. , Steinbeck Katharine S. , Johnston Karen , Walker Jan L. 
Published: September 2006

Abstract
Context: Hyperinsulinism and its associated metabolic abnormalities, including diabetes mellitus (DM), have been reported in long-term survivors of childhood cancer, mainly after bone marrow transplant (BMT); however, the predisposing factors are unclear, and early markers have not been identified.
Methods: The prevalence of overweight/obesity, abdominal adiposity and hyperinsulinemia (HI), impaired glucose tolerance (IGT), or DM was examined prospectively in 248 survivors of childhood cancer (36 prepubertal, 88 pubertal, and 124 adult subjects; 67 BMT) at a median of 12.9 yr (2.3–33.6) after diagnosis and compared with healthy controls. Potential risk factors for the development of HI, IGT, or DM were sought.
Results: Overweight/obesity was not increased when comparing subjects with controls; however, the prevalence of abdominal adiposity in prepubertal and pubertal subjects was roughly doubled (P ≤ 0.04). Fasting insulin concentrations were higher in prepubertal and pubertal subjects compared with their controls (P &lt; 0.001) and were similar in adult and pubertal subjects. HI, IGT, or DM was detected in 39 of 212 (18%) pubertal or adult subjects (23 BMT). Ten of 88 (11%) pubertal and 14 of 124 (11%) adult subjects had IGT/DM (vs. 0 and 4.9% controls, respectively; P &lt; 0.001). Total body irradiation, untreated hypogonadism, and abdominal adiposity emerged as independent risk factors for the development of HI, IGT, or DM in multivariate regression analysis.
Conclusions: The risk factors identified suggest the need for reconsideration of BMT protocols and regular screening of survivors. The increased prevalence of abdominal adiposity among prepubertal subjects, none of whom had developed HI/IGT/DM, suggests that a waist to height ratio greater than 0.5 has potential as a clinical screening tool.
Expression of HIF-1α, HIF-2α (EPAS1), and Their Target Genes in Paraganglioma and Pheochromocytoma with VHL and SDH Mutations
Authors: Pollard Patrick J. , El-Bahrawy Mona , Poulsom Richard , Elia George , Killick Pip , Kelly Gavin , Hunt Toby , Jeffery Rosemary , Seedhar Pooja , Barwell Julian , Latif Farida , Gleeson Michael J. , Hodgson Shirley V. , Stamp Gordon W. , Tomlinson Ian P. M. , Maher Eamonn R. 
Published: September 2006

Abstract
Context: Activation of the hypoxia-inducible transcription factors HIF-1 and HIF-2 and a HIF-independent defect in developmental apoptosis have been implicated in the pathogenesis of pheochromocytoma (PCC) associated with VHL, SDHB, and SDHD mutations.
Objective: Our objective was to compare protein (HIF-1α, EPAS1, SDHB, JunB, CCND1, CD34, CLU) and gene (VEGF, BNIP3) expression patterns in VHL and SDHB/D associated tumors.
Results: Overexpression of HIF-2 was relatively more common in VHL than SDHB/D PCC (12 of 13 vs. 14 of 20, P = 0.02), whereas nuclear HIF-1 staining was relatively more frequent in SDHB/D PCC (19 of 20 vs. 13 of 16, P = 0.04). In addition, CCND1 and VEGF expression (HIF-2 target genes) was significantly higher in VHL than in SDHB/D PCC. These findings suggest that VHL inactivation leads to preferential HIF-2 activation and CCND1 expression as described previously in VHL-defective renal cell carcinoma cell lines but not in other cell types. These similarities between the downstream consequences of VHL inactivation and HIF dysregulation in renal cell carcinoma and PCC may explain how inactivation of the ubiquitously expressed VHL protein results in susceptibility to specific tumor types. Both VHL and SDHB/D PCC demonstrated reduced CLU and SDHB expression. SDHB PCC are associated with a high risk of malignancy, and expression of (proapototic) BNIP3 was significantly lower in SDHB than VHL PCC.
Conclusion: Although inactivation of VHL and SDHB/D may disrupt similar HIF-dependent and HIF-independent signaling pathways, their effects on target gene expression are not identical, and this may explain the observed clinical differences in PCC and associated tumors seen with germline VHL and SDHB/D mutations.
Planned pre‐operative irradiation for carcinoma of the larynx and laryngopharynx treated by total and partial laryngectomy.
Authors: Biller Hugh F. , Ogura Joseph H. , Davis William H. , Powers William E. 
Published: September 2006

AbstractPlanned pre‐operative irradiation for large laryngeal and laryngopharyngeal cancers has been adopted by many surgeons.
Superiorly based pharyngeal flap.
Authors: Skolnik Emanuel M. , Saberman Mark N. , Meyers Robert M. , Ross Joel C. 
Published: September 2006

AbstractVelopharyngeal incompetence may be either congenital or acquired in origin. Congenital defects not only exist as an obvious cleft in the palate but the incompetence may also be a result of more subtle defects such as submucous cleft, platybasia, congenital short palate, or cervical spine deformity. Acquired defects are usually more obvious. Postinflammatory or postirradiation cicatrization and defects after surgical resection are the usual causes, but palate paralysis secondary to neurologic disease and palatal incompetency following adenoidectomy, should also be considered.
Cervical vertigo.
Authors: Jongkees L. B. W. 
Published: September 2006

AbstractIt has been known for decades that movements of the neck can provoke eye movements. Barany1 and Voss2 demonstrated them in newborn children; de Kleyn,3 in rabbits. A sustained torsion of the neck in these circumstances leads to a sustained compensatory eye deviation interrupted by nystagmus beats. In mature humans, turning of the neck causes eye movements only in a patient whose eyes are closed or who are examined in the dark.4,5,6,7,8 Though the combination of compensatory eye movements and nystagmus is found again in this case, the sustained deviation of the eyeball during sustained deviated positions of the neck is not found. Not only neck torsion, but even torsion of the thorax or the pelvis in respect to the adjacent parts of the spine, suffices to elicit nystagmus,4,5 and it must be kept in mind that the angles over which neck, thorax or pelvis must be rotated in order to provoke eye movements need not be extreme. Rotations of 90° or even less, in general, suffice.
Meckel's cartilage remnant?
Authors: Zonis Richard D. 
Published: September 2006

AbstractCASE REPORT. A 12‐year‐old, full blood Pima Indian boy was referred to the otology clinic of the Phoenix Indian Hospital complaining of “something in my ear” found on routine physical examination. The boy had no past or present symptoms related to either ear. On physical examination the right ear was normal. The left revealed a slender, firm, skin‐covered process extending from the anterior canal wall bulge, tapering to a narrow insertion on the malleus, just inferior to the short process (Fig. 1). The tympanic membrane was otherwise normal and moved well on pneumo‐massage. Audiogram was normal (Fig. 2), as were X‐rays of the mandible and temporo‐mandibular joints. Although the boy was asymptomatic, it was felt that the chance of difficulty with accumulation of debris medial to this process was sufficient to advise surgical removal. On December 27, 1967, under general anesthesia, the attachment to the malleus was severed with a sickle knife and the anomalous process removed with a curette. It was softer in consistency than expected. Pathologic examination revealed normal cartilage (Fig. 3). Postoperative course was uneventful. The tympanic membrane was not disturbed. Hearing was unchanged.
Delayed management of facial fractures
Authors: Bernstein Leslie 
Published: September 2006

AbstractIt is generally agreed that best results in the treatment of facial fractures may be expected if the reduction is done within the first few days after the injury; unfortunately, due to a number of factors, this is not always possible. Excluding inevitable delay associated with distance from a suitable medical unit, and failure of complete diagnosis and appreciation of the facial injury, the most frequent reasons for delaying the treatment of facial fractures are serious concomitant injuries which take precedence in management. The most common of these, and certainly the most serious, is a cerebral injury; yet, despite the fact that neurologic levels usually become stable within 10 days after injury, some of these accident victims continue to receive attention to their more obvious injuries, and repair of the facial skeleton is frequently postponed too long, and thus, for one reason or another, delay in specific treatment is not an uncommon sequence following admission to hospital.
Importance of vestibulography in the acoustic neurinoma test battery
Authors: Janeke Johan B. , Sommerville Suzanne , Maddox H. Edward , Battin R. Ray 
Published: September 2006

AbstractVestibular, audiological and X‐ray findings on 25 surgically confirmed neurinoma cases were reviewed to determine the diagnostic sensitivity of each in the neurinoma test battery. A comprehensive, retrocochlear audiological and vestibular work‐up was run. X‐ray procedures included posterior fossa myelograms in all but one instance, with all of the patients complaining of some auditory difficulties; progressive hearing loss and tinnitus were the most common complaints with tinnitus as the earliest symptom. Thirty‐six percent of the cases had a retrocochlear audiological pattern, while 60 percent manifested a mixed cochlear and retrocochlear pattern, the remaining 4 percent presented cochlear findings. A correlation between audiological findings and standard X‐ray views revealed that 32 percent of the cases presented equivocal audiometric and negative X‐ray findings, while myelogram were performed on 24 percent of the patients, and all but two. cases were positive. One of these cases revealed negative findings, and the other was equivocal. Our clinical findings indicated that a routine vestibular work‐up provided the indication for a more progressive neurinoma evaluation.