bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammation causes tissue-specific depletion of vitamin B6
Authors: Chiang En-Pei , Smith Donald E , Selhub Jacob , Dallal Gerard , Wang Yi-Cheng , Roubenoff Ronenn 
Published: September 2005

AbstractPreviously we observed strong and consistent associations between vitamin B6 status and several indicators of inflammation in patients with rheumatoid arthritis. Clinical indicators, including the disability score, the length of morning stiffness, and the degree of pain, and biochemical markers, including the erythrocyte sedimentation rate and C-reactive protein levels, were found to be inversely correlated with circulating vitamin B6 levels. Such strong associations imply that impaired vitamin B6 status in these patients results from inflammation. In the present study we examined whether inflammation directly alters vitamin B6 tissue contents and its excretion in vivo. A cross-sectional case-controlled human clinical trial was performed in parallel with experiments in an animal model of inflammation. Plasma and erythrocyte and pyridoxal 5'-phosphate concentrations, urinary 4-pyridoxic acid excretion, and the activity coefficient of erythrocyte aspartate aminotransferase were compared between patients and healthy subjects. Adjuvant arthritis was induced in rats for investigating hepatic and muscle contents as well as the urinary excretion of vitamin B6 during acute and chronic inflammation. Patients with rheumatoid arthritis had low plasma pyridoxal 5'-phosphate compared with healthy control subjects, but normal erythrocyte pyridoxal 5'-phosphate and urinary 4-pyridoxic acid excretion. Adjuvant arthritis in rats did not affect 4-pyridoxic acid excretion or muscle storage of pyridoxal 5'-phosphate, but it resulted in significantly lower pyridoxal 5'-phosphate levels in circulation and in liver during inflammation. Inflammation induced a tissue-specific depletion of vitamin B6. The low plasma pyridoxal 5'-phosphate levels seen in inflammation are unlikely to be due to insufficient intake or excessive vitamin B6 excretion. Possible causes of decreased levels of vitamin B6 are discussed.
Selective estrogen receptor modulators inhibit growth and progression of premalignant lesions in a mouse model of ductal carcinoma in situ
Authors: Namba Ruria , Young Lawrence JT , Maglione Jeannie E , McGoldrick Erik T , Liu Stephenie , Wurz Gregory T , DeGregorio Michael W , Borowsky Alexander D , MacLeod Carol L , Cardiff Robert D , Gregg Jeffrey P 
Published: September 2005

Abstract
Introduction
Ductal carcinoma in situ (DCIS) is a noninvasive premalignant lesion and is considered a precursor to invasive carcinoma. DCIS accounts for nearly 20% of newly diagnosed breast cancer, but the lack of experimentally amenable in vivo DCIS models hinders the development of treatment strategies. Here, we demonstrate the utility of a mouse transplantation model of DCIS for chemoprevention studies using selective estrogen receptor modulators (SERMs). This model consists of a set of serially transplanted lines of genetically engineered mouse mammary intraepithelial neoplasia (MIN) outgrowth (MIN-O) tissue that have stable characteristics. We studied the ovarian-hormone-responsiveness of one of the lines with a particular focus on the effects of two related SERMs, tamoxifen and ospemifene.

Methods
The estrogen receptor (ER) status and ovarian-hormone-dependence of the mouse MIN outgrowth tissue were determined by immunohistochemistry and ovarian ablation. The effects of tamoxifen and ospemifene on the growth and tumorigenesis of MIN outgrowth were assessed at 3 and 10 weeks after transplantation. The effects on ER status, cell proliferation, and apoptosis were studied with immunohistochemistry.

Results
The MIN-O was ER-positive and ovarian ablation resulted in reduced MIN-O growth and tumor development. Likewise, tamoxifen and ospemifene treatments decreased the MIN growth and tumor incidence in comparison with the control (P < 0.01). Both SERMs significantly decreased cell proliferation. Between the two SERM treatment groups, there were no statistically significant differences in MIN-O size, tumor latency, or proliferation rate. In contrast, the ospemifene treatment significantly increased ER levels while tamoxifen significantly decreased them.

Conclusion
Tamoxifen and ospemifene inhibit the growth of premalignant mammary lesions and the progression to invasive carcinoma in a transplantable mouse model of DCIS. The inhibitory effects of these two SERMs are similar except for their effects on ER modulation. These differences in ER modulation may suggest different mechanisms of action between the two related SERMs and may portend different long-term outcomes. These data demonstrate the value of this model system for preclinical testing of antiestrogen or other therapies designed to prevent or delay the malignant transformation of premalignant mammary lesions in chemoprevention.
Hospital-acquired sinusitis is a common cause of fever of unknown origin in orotracheally intubated critically ill patients
Authors: van Zanten Arthur RH , Dixon Mark J , Nipshagen Martine D , de Bree Remco , Girbes Armand RJ , Polderman Kees H 
Published: September 2005

Abstract
Introduction
Sinusitis is a well recognised but insufficiently understood complication of critical illness. It has been linked to nasotracheal intubation, but its occurrence after orotracheal intubation is less clear. We studied the incidence of sinusitis in patients with fever of unknown origin (FUO) in our intensive care unit with the aim of establishing a protocol that would be applicable in everyday clinical practice.

Methods
Sinus X-rays (SXRs) were performed in all patients with fever for which an initial screening (physical examination, microbiological cultures and chest X-ray) revealed no obvious cause. All patients were followed with a predefined protocol, including antral drainage in all patients with abnormal or equivocal results on their SXR.

Results
Initial screening revealed probable causes of fever in 153 of 351 patients (43.6%). SXRs were taken in the other 198 patients (56.4%); 129 had obvious or equivocal abnormalities. Sinus drainage revealed purulent material and positive cultures (predominantly Pseudomonas and Klebsiella species) in 84 patients. Final diagnosis for the cause of fever in all 351 patients based on X-ray results, microbiological cultures, and clinical response to sinus drainage indicated sinusitis as the sole cause of fever in 57 (16.2%) and as contributing factor in 48 (13.8%) patients with FUO. This will underestimate the actual incidence because SXR and drainage were not performed in all patients.

Conclusion
Physicians treating critically ill patients should be aware of the high risk of sinusitis and take appropriate preventive measures, including the removal of nasogastric tubes in patients requiring long-term mechanical ventilation. Routine investigation of FUO should include computed tomography scan, SXR or sinus ultrasonography, and drainage should be performed if any abnormalities are found.
Preferences for place of care and place of death among informal caregivers of the terminally ill
Authors: Brazil Kevin , Howell Doris , Bedard Michel , Krueger Paul , Heidebrecht Christine 
Published: September 2005

Objectives: (1) To determine informal caregivers perceptions about place of care and place of death; and (2) to identify variables associated with a home death among terminally ill individuals who received in–home support services in a publicly funded home care system. Participants and design: A total of 216 informal caregivers participated in a bereavement interview. Data collection included care recipient and informal caregiver characteristics, the use of and satisfaction with community services, and preferences about place of death. Results: Most caregivers reported that they and the care recipient had a preferred place of death (77 and 68%, respectively) with over 63% reporting home as the preferred place of death. Caregivers had a greater preference for an institutional death (14%) than care recipients (4.7%). While 30% of care recipients did not die in their preferred location, most caregivers (92%) felt, in retrospect, that where the care recipient died was the appropriate place of death. Most caregivers reported being satisfied with the care that was provided. The odds of dying at home were greater when the care recipient stated a preference for place of death (OR: 2.92; 95% CI: 1.25, 6.85), and the family physician made home visits during the care recipients last month of life (Univariate odds ratios (OR): 4.42; 95% CI: 1.46, 13.36). Discussion: The ethic of self–control and choice for the care recipient must be balanced with consideration for the well being of the informal caregiver and responsiveness of the community service system.
Assessing Benefit and Risk in the Prevention of Prostate Cancer: The Prostate Cancer Prevention Trial Revisited
Authors: Klein Eric A. , Tangen Catherine M. , Goodman Phyllis J. , Lippman Scott M. , Thompson Ian M. 
Published: September 2005

Purpose The Prostate Cancer Prevention Trial demonstrated a 25% reduction in period prevalence of prostate cancer in men randomly assigned to 5 mg/d of finasteride. However, widespread use of finasteride for prevention is inhibited by the observed increased risk of high-grade disease. We present a model of risk and benefit that estimates the potential effects of histologic artifact in the assignment of excess risk for high-grade disease and the possible effect of overdetection bias introduced by finasteride-induced volume reduction. Methods The absolute benefit/absolute risk ratio of finasteride use was estimated by calculating the ratio of absolute risk reduction in the finasteride arm to the absolute risk of excess high-grade cancers. This ratio was recalculated for assumptions that 10%, 25%, or 50% of the excess high-grade cancers were due to histologic artifact, and that there was a 25% overdetection bias in the finasteride arm. Results For all cancers the absolute benefit/absolute risk ratio increased from 4.6:1 to 5.1:1, 6.2:1, and 9.2:1 for assumptions of 10%, 25%, or 50% histologic artifact, respectively. The ratio increased from 4.6:1 to 8.2:1 for the assumption of 25% overdetection bias, and to 9.1:1, 10.9:1, and 16.3:1 for combined assumptions of 25% overdetection bias and 10%, 25%, or 50% histologic artifact, respectively. Conclusion The adoption of a prevention strategy hinges on potential benefits weighed against potential risks. This model demonstrates the magnitude of effect for a hypothesized range of histologic artifact and overdetection bias on the assessment of risk versus benefit for finasteride.
Assessment of Quality of Life in the Supportive Care Setting of the Big Lung Trial in Non–Small-Cell Lung Cancer
Authors: Brown J. , Thorpe H. , Napp V. , Fairlamb D.J. , Gower N.H. , Milroy R. , Parmar M.K.B. , Rudd R.M. , Spiro S.G. , Stephens R.J. , Waller D. , West P. , Peake M.D. 
Published: September 2005

Purpose The Big Lung Trial (BLT) was a large, pragmatic trial to evaluate the addition of chemotherapy to primary treatment (ie, surgery, radical radiotherapy, or supportive care) in non–small-cell lung cancer (NSCLC). In the supportive care group, there was a small but significant survival benefit in patients treated with chemotherapy compared with supportive care alone (no chemotherapy). A substudy was undertaken to evaluate the quality of life (QoL) implications of the treatment options. QoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires C30 (QLQ-C30) and LC17, and daily diary cards. Patients and Methods EORTC QLQ-C30 and LC17 were collected at 0, 6 to 8, 12, 18, and 24 weeks. Diary cards were completed during the first 12 weeks of the study. The primary end point was global QoL at 12 weeks. Results A total of 273 patients were randomly assigned: 138 to no chemotherapy and 135 to chemotherapy. There was no evidence of a large detrimental effect on QoL of chemotherapy. No statistically significant differences in global QoL or physical/emotional functioning, fatigue and dyspnea, and pain were detected at 12 weeks. Higher rates of palliative radiotherapy in the no chemotherapy arm may have lessened differences in QoL. Global QoL, role functioning, fatigue, appetite loss, and constipation were prognostic indicators of survival at 12 weeks. Conclusion There were no important adverse effects of chemotherapy on QoL.
Assessment of Quality of Life in MA.17: A Randomized, Placebo-Controlled Trial of Letrozole After 5 Years of Tamoxifen in Postmenopausal Women
Authors: Whelan Timothy J. , Goss Paul E. , Ingle James N. , Pater Joseph L. , Tu Dongsheng , Pritchard Kathleen , Liu Shifang , Shepherd Lois E. , Palmer Michael , Robert Nicholas J. , Martino Silvana , Muss Hyman B. 
Published: September 2005

Purpose To evaluate the impact of letrozole compared with placebo after adjuvant tamoxifen on quality of life (QOL) in the MA.17 trial. Methods Patients completed the Short Form 36-item Health Survey (SF-36) and the Menopause Specific Quality of Life Questionnaire (MENQOL) at baseline, 6 months, and annually. Mean change scores from baseline were compared between groups for summary measures and domains. A response analysis compared the proportion of patients who demonstrated an important change in QOL. Results Of 5,187 randomly assigned women in the trial, 3,612 (69.9%) participated in the QOL substudy: 1,799 were allocated to placebo and 1,813 were allocated to letrozole. No differences were seen between groups in mean change scores from baseline for the SF-36 physical and mental component summary scores at 6, 12, 24, and 36 months. Small (< 0.2 standard deviations) but statistically significant differences in mean change scores from baseline were seen for the SF-36 domains of physical functioning (12 months), bodily pain (6 months) and vitality (6 and 12 months), and the MENQOL vasomotor (6, 12, and 24 months) and sexual domains (12 and 24 months). On the response analysis, a significant difference was seen between groups for the bodily pain domain (percentage of patients reporting a worsening of QOL, 47% placebo v 51% letrozole; P = .009) and the vasomotor domain (22% placebo v 29% letrozole; P = .001). Conclusion Letrozole did not have an adverse impact on overall QOL. Small effects were seen in some domains consistent with a minority of patients experiencing changes in QOL compatible with a reduction in estrogen synthesis.
Outcome of Shunting in Idiopathic Normal-pressure Hydrocephalus and the Value of Outcome Assessment in Shunted Patients
Authors: Klinge Petra , Marmarou Anthony , Bergsneider Marvin , Relkin Norman , Black Peter McL. 
Published: September 2005

Abstract

OBJECTIVE:
To develop guidelines for assessing shunt outcome in patients with idiopathic normal-pressure hydrocephalus (INPH). To date, the literature available on this topic has been marked by disparate definitions of clinical improvement, varying postoperative follow-up protocols and periods, and substantial differences in the postoperative management. Because specific criteria for defining clinical improvement are seldom reported, conclusions drawn about shunt outcome may be subjective.

METHODS:
A MEDLINE search back to 1966 was undertaken using the query NPH, normal-pressure hydrocephalus, shunting, shunt treatment, shunt response, outcome, and clinical outcome. The criteria for selection were studies that included INPH from 1966 to the present in which the outcome of INPH was reported in patient groups of 20 or more.

RESULTS:
To date, there is no standard for outcome assessment of shunt treatment in INPH. The variable improvement rates reported are not only because of different criteria for selection of patients but also because of different postoperative assessment procedures and follow-up intervals.

CONCLUSION:
Studies that have established fixed protocols for follow-up have shown that short- and long-term periods after shunting are determined by many factors. Whereas short-term results were more likely to be influenced by shunt-associated risks, long-term results were independent of factors inherent to the shunt procedure and shunt complications, i.e., death and morbidity related to concomitant cerebrovascular and vascular diseases. Studies have shown that beyond 1 year after surgery, these factors definitely influence the clinical effect of shunting, making the 1-year postshunt period a potential determinant of the shunt outcome. Guidelines for outcome assessment were developed on the basis of the available evidence and consensus of expert opinion.
Emerging Concepts in the Treatment of Intracranial Aneurysms: Stents, Coated Coils, and Liquid Embolic Agents
Authors: Lanzino Giuseppe , Kanaan Yassine , Perrini Paolo , Dayoub Hayan , Fraser Kenneth 
Published: September 2005

ABSTRACT
ENDOVASCULAR TECHNIQUES FOR the treatment of intracranial aneurysms are rapidly evolving. Modifications of more traditional coils have been introduced. Such modifications include newer coils coated with various polymers to increase both coil thrombogenicity and degree of aneurysm packing. In addition, newer coil designs aimed at improving the conformability of the coil to the aneurysm have been used with promising preliminary results. The availability of a newer generation of stents specifically designed for intracranial navigation allows for more effective treatment of aneurysms with wide necks, which usually have been considered unsuitable for optimal endovascular treatment. Endovascular alternatives to coil embolization, such as liquid embolic materials, also have been explored for the treatment of intracranial aneurysms, with varying results. We summarize the rationale for use of these newer devices and early clinical experiences. Areas of current research and future directions of endovascular aneurysm treatment also are discussed.
In Vivo Optical Spectroscopy Detects Radiation Damage in Brain Tissue
Authors: Lin Wei-Chiang , Mahadevan-Jansen Anita , Johnson Mahlon D. , Weil Robert J. , Toms Steven A. 
Published: September 2005

ABSTRACT

OBJECTIVE:
Magnetic resonance imaging abnormalities in malignant brain tumors after irradiation may represent either recurrent tumor or radiation injury. Optical spectroscopy may represent a novel technique to identify radiation damage in brain tissues and to differentiate contrast-enhancing lesions from recurrent tumor.

METHODS:
Fluorescence and diffuse reflectance spectra were acquired from 90 patients: 15 undergoing surgical resection for presumed recurrent tumor after radiation therapy, 15 with epilepsy and hippocampal sclerosis, and 60 with tumors who had not received irradiation. Optical spectra were acquired from 6 to 10 sites and were compared with a biopsy obtained from beneath the optical spectroscopy probe; the data then were classified by a neuropathologist blinded to the spectroscopy data. A probe for the intraoperative collection of diffuse reflectance and fluorescence spectra was used.

RESULTS:
Thirteen of 15 patients (29 of 129 spectra) with previous irradiation showed a unique spectral feature characterized by a fluorescence peak centered at 500 nm (F500). All biopsy specimens showing histopathological signs of radiation injury had the F500 on their corresponding spectra (18 of 18). The F500 was identified in another 10% (11 of 111 spectra) of samples with previous irradiation but no histologically identifiable signs of radiation damage. The F500 was never seen in the normal temporal lobe of epilepsy patients with hippocampal sclerosis (0 of 105) and was seen in only 1.5% of tumor patients who did not undergo previous irradiation (6 of 433).

CONCLUSION:
Optical spectroscopy detects radiation damage in brain tissues. The F500 spectral peak may allow accurate selection of tissues for biopsy in evaluating patients with new, contrast-enhancing lesions in the setting of previous irradiation.
Altered Flow Territories after Extracranial-Intracranial Bypass Surgery
Authors: Hendrikse Jeroen , van der Zwan Albert , Ramos Lino M.P. , van Osch Matthias J.P. , Golay Xavier , Tulleken Cees A.F. , van der Grond Jeroen 
Published: September 2005

ABSTRACT

OBJECTIVE:
To prevent stroke after carotid sacrifice and to augment cerebral perfusion in patients with internal carotid artery (ICA) occlusion, high-flow extracranial-intracranial (EC-IC) bypass operations are performed. Although the function and efficacy of the bypass is monitored during surgery, the postoperative flow through the bypass is significantly lower than the flow in the contralateral ICA. Thus far, it is unknown whether decreased bypass flow is caused by a low tissue perfusion or by a relatively small flow territory.

METHODS:
Seven patients, four with an atherosclerotic ICA occlusion and three with a giant aneurysm of the ICA, were investigated; each underwent a high-flow EC-IC bypass and permanent occlusion of the ICA. Cerebral blood flow was measured with arterial spin labeling perfusion magnetic resonance imaging. Separate flow territory mapping of the EC-IC bypass, contralateral ICA, and posterior circulation was performed with selective arterial spin labeling magnetic resonance imaging.

RESULTS:
No significant difference was found in cerebral blood flow between the hemisphere ipsilateral to the EC-IC bypass (70.9 ± 11.3 ml/min/100 g tissue), contralateral to the EC-IC bypass (71.9 ± 14.3 ml/min/100 g tissue), and comparable findings in 50 healthy control participants (69.1 ± 17.5 ml/min/100 g tissue). Paired analysis of the individual flow territories demonstrated a 15% volume reduction (P = 0.018) in flow territory of the EC-IC bypass compared with the contralateral side.

CONCLUSION:
In the present study, we demonstrate the feasibility of selective arterial spin labeling magnetic resonance imaging for clinical follow-up of patients after high-flow EC/IC bypass surgery, providing both information on flow territories and the level of regional cerebral blood flow.
Avulsion Fracture of the Foramen Magnum Treated with Occiput-to-C1 Fusion: Technical Case Report
Authors: Maughan Peter H. , Horn Eric M. , Theodore Nicholas , Feiz-Erfan Iman , Sonntag Volker K.H. 
Published: September 2005

ABSTRACTOBJECTIVE AND IMPORTANCE:A 31-year-old woman presented with an avulsion fracture of the foramen magnum via bilateral occipital condyles with extension through the inferior aspect of the clivus.CLINICAL PRESENTATION:The patient had no neurological deficits and was initially immobilized in a halo brace.INTERVENTION:To preserve rotational motion at C1–C2, we performed an occiput-to-C1 fusion with bilateral C1 lateral mass screws attached with rods to occipital keel screws. Postoperatively, the patient remained neurologically intact. Three-month follow-up imaging revealed no abnormal motion. Follow-up computed tomographic scan showed an intact construct and bony fusion.CONCLUSION:This rare injury, a bony variant of occipitoatlantal dislocation, was successfully treated with a unique occiput-to-C1 fusion.