bluuebunny/crossref_metadata_2025 huggingface dataset:
Levetiracetam: A Practical Option for Seizure Management in Elderly Patients With Cognitive Impairment
Authors: Lippa Carol F. , Rosso Andrea , Hepler Marjorie , Jenssen Sigmund , Pillai Jyoti , Irwin David
Published: November 2008

Cognitive impairment and seizures are common in our aging population. Anticonvulsant treatment is problematic due to sedation, cognitive slowing, and behavioral changes. Levetiracetam has favorable pharmacokinetics, good efficacy in elderly individuals, a favorable side effect profile, and lacks major drug interactions. We conducted a prospective, uncontrolled, phase 4, open label, 12-week study of levetiracetam to better profile its efficacy, safety, and impact on cognitive/behavioral status in 24 cognitively impaired, elderly individuals. In total, 69% were seizure free for the duration of the study; the remaining participants had satisfactory seizure control. Fatigue was the most common side effect (5 participants). Significant overall improvements were observed for the Folstein’s Mini-Mental State Examination and the Alzheimer’s Disease Assessment Scale—Cognitive. No significant changes were seen in behavioral or functional measures. Levetiracetam is an effective antiepileptic drug in elderly individuals with cognitive impairment. At 3 months, participants who remained on levetiracetam showed excellent cognitive tolerability.
Challenging gold based filler metals for uses in medicine
Authors: Bobzin K. , Lugscheider E. , Ernst F. , Rösing J. , Ferrara S.
Published: November 2008

Research has been carried out to investigate new soldering materials and technologies for the medical field. The two soldering techniques, which have been considered, are diffusion and active soldering. In order to satisfy the most important medical requirement, the biocompatibility, gold based solders and soldering systems have been studied. According to the Directive 2002/95/EC of the European Parliament, lead as well as cadmium, hexavalent chromium and mercury have not been alloyed in the developed solders. The examined soldering systems enable joining similar and dissimilar materials, which is essential in the field of hybrid microsystems engineering. Furthermore, the achieved low process temperatures reduce the incidence of damage and thermally induced stresses in the components being joined.
Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases
Authors: Joshi Ila , Minter Lisa M. , Telfer Janice , Demarest Renée M. , Capobianco Anthony J. , Aster Jon C. , Sicinski Piotr , Fauq Abdul , Golde Todd E. , Osborne Barbara A.
Published: November 2008

Notch signaling plays a role in normal lymphocyte development and function. Activating Notch1-mutations, leading to aberrant downstream signaling, have been identified in human T-cell acute lymphoblastic leukemia (T-ALL). While this highlights the contribution of Notch signaling to T-ALL pathogenesis, the mechanisms by which Notch regulates proliferation and survival in normal and leukemic T cells are not fully understood. Our findings identify a role for Notch signaling in G1-S progression of cell cycle in T cells. Here we show that expression of the G1 proteins, cyclin D3, CDK4, and CDK6, is Notch-dependent both in vitro and in vivo, and we outline a possible mechanism for the regulated expression of cyclin D3 in activated T cells via CSL (CBF-1, mammals; suppressor of hairless, Drosophila melanogaster; Lag-1, Caenorhabditis elegans), as well as a noncanonical Notch signaling pathway. While cyclin D3 expression contributes to cell-cycle progression in Notch-dependent human T-ALL cell lines, ectopic expression of CDK4 or CDK6 together with cyclin D3 shows partial rescue from γ-secretase inhibitor (GSI)-induced G1 arrest in these cell lines. Importantly, cyclin D3 and CDK4 are highly overexpressed in Notch-dependent T-cell lymphomas, justifying the combined use of cell-cycle inhibitors and GSI in treating human T-cell malignancies.
Accuracy of death certification and hospital record linkage for identification of incident stroke
Authors: Sinha Shubhada , Myint Phyo K , Luben Robert N , Khaw Kay-Tee
Published: November 2008

Background

There is little information on the validity of using record linkage with routinely collected data for case ascertainment of stroke in large population-based studies in the UK. We examined the accuracy of these routine record linkage approaches for identifying incident stroke cases in a large UK population-based study, the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort.

Methods

We examined a sample of hospital records of incident stroke cases identified by linkage with two routine data sources, death certificates and a national hospital record linkage system (ENCORE), using predefined study criteria. Two senior Specialist Registrars with clinical experience in stroke medicine examined the hospital records and searched for the evidence of stroke recorded in these records between 1993/97–2003.

Results

Of 520 incident strokes identified between 1993/1997–2003 using record linkage systems in the EPIC-Norfolk, a sample of 250 medical case notes were examined between March and July 2004. Using the predefined study criteria, there were 191 definite strokes (76%), 20 probable strokes (8%), 11 possible strokes and 11 cases of transient ischaemic attacks (4% each) i.e. 233/250 (93%) with possible or definite stroke or transient ischaemic attacks. Stroke could not be verified using hospital records in 13 cases (5%) and 4 cases (2%) had other diagnoses: 3 cases of vascular dementia and 1 case of benign intracranial hypertension. The diagnosis of stroke in 185 out of 250 cases identified in the EPIC-Norfolk (74.0%) was supported by radiological evidence using WHO criteria.

Conclusion

Death certificates and hospital record linkage in this British prospective study have a high accuracy or positive predictive value in correctly identifying incident stroke cases.
Predictors of gastrointestinal lesions on endoscopy in iron deficiency anemia without gastrointestinal symptoms
Authors: Majid Shahid , Salih Mohammad , Wasaya Rozina , Jafri Wasim
Published: November 2008

Background

Iron deficiency anaemia (IDA) due to occult gastrointestinal (GI) blood loss usually remains unnoticed until patient become symptomatic. There is sparse data in IDA patients without gastrointestinal symptoms. This study was designed to find out the frequency and predictors of endoscopic lesions in IDA without gastrointestinal symptoms. Cross-sectional study performed on a convenience sample of consecutive subjects.

Methods

Ninety five consecutive patients with laboratory based diagnosis of IDA having no gastrointestinal symptoms were interviewed and their clinical and biochemical variables were recorded. All the study patients underwent esophago-gastroduodenoscopy (EGD) and colonoscopy. Endoscopic findings were documented as presence/absence of bleeding related lesion and presence/absence of cause of IDA. Multiple logistic regressions were performed to identify variables significantly related to outcome variables.

Results

Possible cause of anaemia was found in 71% and bleeding related lesions were found in 53% of patients. Upper gastrointestinal tract lesions were found in 41% of patients with bleeding related lesions. On multivariable logistic regression; advancing age, low mean corpuscular volume (MCV ≤ 60 fl), and positive fecal occult blood test were predictive factors for bleeding related GI lesions and cause of IDA

Conclusion

Clinical and Biochemical markers can predict gastrointestinal lesions on endoscopy in IDA patients without gastrointestinal symptoms. High proportion of upper gastrointestinal involvement warrants EGD as initial endoscopic procedure however, this needs validation by further studies.
Streptococcus intermedius causing infective endocarditis and abscesses: a report of three cases and review of the literature
Authors: Tran MaryAnn P , Caldwell-McMillan Molly , Khalife Walid , Young Vincent B
Published: November 2008

Background

Streptococcus intermedius is a member of the Streptococcus anginosus group. Clinical disease with S. intermedius is characterized by abscess formation and rarely endocarditis. Identification of Streptococcus intermedius is difficult, leading to the development of molecular methods to more accurately identify and characterize this organism.

Case presentation

Over a period of 6 months we encountered three cases of invasive Streptococcus intermedius infection presenting as hepatic abscesses, brain abscess, and endocarditis. We confirmed our microbiologic diagnosis through 16S sequencing and found a common virulence gene in each case.

Conclusion

Our report illustrates three different clinical manifestations due to Streptococcus intermedius infection that can be encountered in healthy individuals in a community hospital setting. To our knowledge, this is the first case of Streptococcus intermedius endocarditis confirmed by 16S sequencing analysis. The use of molecular methods may allow a better understanding of the epidemiology and pathogenesis of this organism.
Frameshift mutations in coding repeats of protein tyrosine phosphatase genes in colorectal tumors with microsatellite instability
Authors: Korff Sebastian , Woerner Stefan M , Yuan Yan P , Bork Peer , von Knebel Doeberitz Magnus , Gebert Johannes
Published: November 2008

Background

Protein tyrosine phosphatases (PTPs) like their antagonizing protein tyrosine kinases are key regulators of signal transduction thereby assuring normal control of cellular growth and differentiation. Increasing evidence suggests that mutations in PTP genes are associated with human malignancies. For example, mutational analysis of the tyrosine phosphatase (PTP) gene superfamily uncovered genetic alterations in about 26% of colorectal tumors. Since in these studies tumors have not been stratified according to genetic instability status we hypothesized that colorectal tumors characterized by high-level of microsatellite instability (MSI-H) might show an increased frequency of frameshift mutations in those PTP genes that harbor long mononucleotide repeats in their coding region (cMNR).

Results

Using bioinformatic analysis we identified 16 PTP candidate genes with long cMNRs that were examined for genetic alterations in 19 MSI-H colon cell lines, 54 MSI-H colorectal cancers, and 17 MSI-H colorectal adenomas. Frameshift mutations were identified only in 6 PTP genes, of which PTPN21 show the highest mutation frequency at all in MSI-H tumors (17%).

Conclusion

Although about 32% of MSI-H tumors showed at least one affected PTP gene, and cMNR mutation rates in PTPN21, PTPRS, and PTPN5 are higher than the mean mutation frequency of MNRs of the same length, mutations within PTP genes do not seem to play a common role in MSI tumorigenesis, since no cMNR mutation frequency reached statistical significance and therefore, failed prediction as a Positive Selective Target Gene.
Giant breast tumors: Surgical management of phyllodes tumors, potential for reconstructive surgery and a review of literature
Authors: Liang Margaret I , Ramaswamy Bhuvaneswari , Patterson Cynthia C , McKelvey Michael T , Gordillo Gayle , Nuovo Gerard J , Carson William E
Published: November 2008

Background

Phyllodes tumors are biphasic fibroepithelial neoplasms of the breast. While the surgical management of these relatively uncommon tumors has been addressed in the literature, few reports have commented on the surgical approach to tumors greater than ten centimeters in diameter – the giant phyllodes tumor.

Case presentation

We report two cases of giant breast tumors and discuss the techniques utilized for pre-operative diagnosis, tumor removal, and breast reconstruction. A review of the literature on the surgical management of phyllodes tumors was performed.

Conclusion

Management of the giant phyllodes tumor presents the surgeon with unique challenges. The majority of these tumors can be managed by simple mastectomy. Axillary lymph node metastasis is rare, and dissection should be limited to patients with pathologic evidence of tumor in the lymph nodes.
Lung adenocarcinoma presenting as obstructive jaundice: a case report and review of literature
Authors: Pericleous Stephanos , Mukherjee Samrat , Hutchins Robert R
Published: November 2008

Background

Lung cancer is known to metastasize to the pancreas with several case reports found in the literature, however, most patients are at an advanced stage and receive palliative treatment.

Case presentation

We describe the case of a 56 year old male patient who presented with a picture of obstructive jaundice. Investigations revealed an obstructing lesion in the pancreas and a further lesion in the lung with benign appearances. The patient underwent a pancreatectomy and, unexpectedly, the histology of the resected specimen demonstrated metastatic adenocarcinoma of bronchogenic origin. He was referred to a cardiothoracic team who proceeded to resect the patient's thoracic lesion before administration of adjuvant chemotherapy. The patient was reviewed 18 months post operatively and remains symptom free with no clinical or radiological evidence of recurrence. We were unable to identify any previous case reports (of lung adenocarcinoma) with such a presentation which were ultimately treated with resection of both lesions.

Conclusion

Similar situations are bound to arise again in the future and we believe that this report could demonstrate that there is a case for aggressive surgical management in a highly selected group of patients: those with NSCLC and a synchronous solitary pancreatic deposit.
Field validation of listings of food stores and commercial physical activity establishments from secondary data
Authors: Paquet Catherine , Daniel Mark , Kestens Yan , Léger Karine , Gauvin Lise
Published: November 2008

Background

Food- and activity-related establishments are increasingly viewed as neighbourhood resources that potentially condition health-related behaviour. The primary objective of the current study was to establish, using ground truthing (on-site verification), the validity of measures of availability of food stores and physical activity establishments that were obtained from commercial database and Internet searches. A secondary objective was to examine differences in validity results according to neighbourhood characteristics and commercial establishment categories.

Methods

Lists of food stores and physical activity-related establishments in 12 census tracts within the Montreal metropolitan region were compiled using a commercial database (n = 171 establishments) and Internet search engines (n = 123 establishments). Ground truthing through field observations was performed to assess the presence of listed establishments and identify those absent. Percentage agreement, sensitivity (proportion of establishments found in the field that were listed), and positive predictive value (proportion of listed establishments found in the field) were calculated and contrasted according to data sources, census tracts characteristics, and establishment categories.

Results

Agreement with field observations was good (0.73) for the commercial list, and moderate (0.60) for the Internet-based list. The commercial list was superior to the Internet-based list for correctly listing establishments present in the field (sensitivity), but slightly inferior in terms of the likelihood that a listed establishment was present in the field (positive predictive value). Agreement was higher for food stores than for activity-related establishments.

Conclusion

Commercial data sources may provide a valid alternative to field observations and could prove a valuable tool in the evaluation of commercial environments relevant to eating behaviour. In contrast, this study did not find strong evidence in support of commercial and Internet data sources to represent neighbourhood opportunities for active lifestyle.
Mitochondrial concept of leukemogenesis: key role of oxygen-peroxide effects
Authors: Lyu Boris N , Ismailov Sanzhar B , Ismailov Bolat , Lyu Marina B
Published: November 2008

Background and hypothesis

The high sensitivity of hematopoietic cells, especially stem cells, to radiation and to pro-oxidative and other leukemogenic agents is related to certain of their morphological and metabolic features. It is attributable to the low (minimal) number of active mitochondria and the consequently slow utilization of O2 entering the cell. This results in an increased intracellular partial pressure of O2 (pO2) and increased levels of reactive oxygen (ROS) and nitrogen (RNS) species, and a Δ(PO – AO) imbalance between the pro-oxidative (PO) and antioxidative (AO) constituents.

Proposed mechanism

Because excessive O2 is toxic, we suggest that hematopoietic cells exist in a kind of unstable dynamic balance. This suggestion is based on the idea that mitochondria not only consume O2 in the process of ATP production but also constitute the main anti-oxygenic stage in the cell's protective antioxidative system. Variations in the mitochondrial base capacity (quantity and quality of mitochondria) constitute an important and highly efficient channel for regulating the oxidative stress level within a cell.

The primary target for leukemogenic agents is the few mitochondria within the hematopoietic stem cell. Disturbance and weakening of their respiratory function further enhances the initial pro-oxidative state of the cell. This readily results in peroxygenation stress, creating the necessary condition for inducing leukemogenesis. We propose that this is the main cause of all related genetic and other disorders in the cell. ROS, RNS and peroxides act as signal molecules affecting redox-sensitive transcription factors, enzymes, oncogenes and other effectors. Thereby, they influence the expression and suppression of many genes, as well as the course and direction of proliferation, differentiation, leukemogenesis and apoptosis.

Differentiation of leukemic cells is blocked at the precursor stage. While the transformation of non-hematopoietic cells into tumor cells starts during proliferation, hematopoietic cells become leukemic at one of the interim stages in differentiation, and differentiation does not continue beyond that point. Proliferation is switched to differentiation and back according to a trigger principle, again involving ROS and RNS. When the leukemogenic ΔL(PO – AO) imbalance decreases in an under-differentiated leukemia cell to the differentiation level ΔD(PO – AO), the cell may continue to differentiate to the terminal stage.

Conclusion

The argument described in this article is used to explain the causes of congenital and children's leukemia, and the induction of leukemia by certain agents (vitamin K3, benzene, etc.). Specific research is required to validate the proposals made in this article. This will require accurate and accessible methods for measuring and assessing oxidative stress in different types of cells in general, and in hematopoietic cells in particular, in their different functional states.
The YPLGVG sequence of the Nipah virus matrix protein is required for budding
Authors: Patch Jared R , Han Ziying , McCarthy Sarah E , Yan Lianying , Wang Lin-Fa , Harty Ronald N , Broder Christopher C
Published: November 2008

Background

Nipah virus (NiV) is a recently emerged paramyxovirus capable of causing fatal disease in a broad range of mammalian hosts, including humans. Together with Hendra virus (HeV), they comprise the genus Henipavirus in the family Paramyxoviridae. Recombinant expression systems have played a crucial role in studying the cell biology of these Biosafety Level-4 restricted viruses. Henipavirus assembly and budding occurs at the plasma membrane, although the details of this process remain poorly understood. Multivesicular body (MVB) proteins have been found to play a role in the budding of several enveloped viruses, including some paramyxoviruses, and the recruitment of MVB proteins by viral proteins possessing late budding domains (L-domains) has become an important concept in the viral budding process. Previously we developed a system for producing NiV virus-like particles (VLPs) and demonstrated that the matrix (M) protein possessed an intrinsic budding ability and played a major role in assembly. Here, we have used this system to further explore the budding process by analyzing elements within the M protein that are critical for particle release.

Results

Using rationally targeted site-directed mutagenesis we show that a NiV M sequence YPLGVG is required for M budding and that mutation or deletion of the sequence abrogates budding ability. Replacement of the native and overlapping Ebola VP40 L-domains with the NiV sequence failed to rescue VP40 budding; however, it did induce the cellular morphology of extensive filamentous projection consistent with wild-type VP40-expressing cells. Cells expressing wild-type NiV M also displayed this morphology, which was dependent on the YPLGVG sequence, and deletion of the sequence also resulted in nuclear localization of M. Dominant-negative VPS4 proteins had no effect on NiV M budding, suggesting that unlike other viruses such as Ebola, NiV M accomplishes budding independent of MVB cellular proteins.

Conclusion

These data indicate that the YPLGVG motif within the NiV M protein plays an important role in M budding; however, involvement of any specific components of the cellular MVB sorting pathway in henipavirus budding remains to be demonstrated. Further investigation of henipavirus assembly and budding may yet reveal a novel mechanism(s) of viral assembly and release that could be applicable to other enveloped viruses or have therapeutic implications.
Timing of supplementation of selenium and isoflavones determines prostate cancer risk factor reduction in rats
Authors: Tolman Jessica R , Lephart Edwin D , Setchell Kenneth DR , Eggett Dennis L , Christensen Merrill J
Published: November 2008

Background

High dietary intake of selenium or isoflavones reduces risk factors for prostate cancer. We tested whether combined supplementation of these two dietary components would reduce prostate cancer risk factors in rats more than supplementation of each component individually.

Methods

Male Noble rat pups were exposed from conception to diets containing an adequate (0.33–0.45 mg/kg diet) or high (3.33–3.45 mg/kg) concentration of selenium as Se-methylselenocysteine and a low (10 mg/kg) or high (600 mg/kg) level of isoflavones in a 2 × 2 factorial design. Pups consumed their respective diets until sacrifice at 35, 100, or 200 days. Male Noble rat breeders, whose exposure to the diets began after puberty, were sacrificed at 336 days. Rats were weighed biweekly. Blood was collected at the time of sacrifice and body fat and prostates were dissected and weighed. Serum levels of leptin, IGF-1, and testosterone were determined using ELISA kits. Serum levels of isoflavones were assayed by GC/MS. Liver activity of selenium-dependent glutathione peroxidase 1 was measured as an indicator of selenium status.

Results

Serum isoflavone concentrations were nearly 100-fold higher at 35 days of age (1187.1 vs. 14.4 ng/mL, mean ± SD) in pups fed the high vs. low isoflavone diets, and remained so at 100 and 200 days, and in breeders. There were no dietary differences in liver glutathione peroxidase activity in pups or breeders. High isoflavone intake significantly (p = 0.001–0.047) reduced body weight in rat pups from 35 days onward, but not in breeders. Body fat and leptin were likewise significantly reduced by high isoflavones in pups while effects in breeders were less pronounced but still significant. High intake of Se and isoflavones each decreased serum IGF-1 in pups at 100 and 200 days, but not in breeders. No consistent dietary effects were observed on serum testosterone or relative weights of prostates. In pups, the combination of high isoflavones and high selenium produced the lowest weight gain, the lowest serum leptin, and the lowest serum IGF-1 concentrations of all four diets.

Conclusion

Combined intake of high selenium and high isoflavones may achieve greater chemopreventive effects than either compound individually. The timing of supplementation may determine the significance of its effects.
Z factor: A New Index for Measuring Academic Research Output
Authors: Zhuo Min
Published: November 2008

With rapid progress in scientific research activities and growing competition for funding resources, it becomes critical to effectively evaluate an individual researcher's annual academic performance, or their cumulative performance within the last 3–5 years. It is particularly important for young independent investigators, and is also useful for funding agencies when determining the productivity and quality of grant awardees. As the funding becomes increasingly limited, having an unbiased method of measuring recent performance of an individual scientist is clearly needed. Here I propose the Z factor, a new and useful way to measure recent academic performance.
Can only intelligent children do mind reading: The relationship between intelligence and theory of mind in 8 to 11 years old
Authors: Rajkumar Anto P , Yovan Simpson , Raveendran Anoop L , Russell Paul Swamidhas Sudhakar
Published: November 2008

Background

The mind reading ability of children has evoked wide interest, but its relationship with general cognitive abilities remains obscure.

Methods

We studied the relationship between the mind reading ability and general intelligence. Children (N = 105) between 8 to 11 years from educational institutions were assessed for the mind reading ability using Picture Sequencing Task and Unexpected Contents Theory of Mind task. We used Strengths and Difficulties Questionnaire to rule out psychiatric morbidity. An independent investigator quantified intelligence and adaptive behavior with Binet- Kamat Test of intelligence and Vineland Adaptive Behavior Scale respectively. We employed bivariate and multivariate statistical tests.

Results

We demonstrated that mind reading ability was not significantly related to general intelligence or its domains except for the social intelligence after controlling the confounders methodologically and statistically.

Conclusion

These findings argue that mind reading skill exists as an independent cognitive domain and has clinical, research as well as educational implications.
Traumatic unilateral lumbosacral jumped facet without fracture in a child – presentation of a safe treatment strategy for a rare injury
Authors: Szentirmai Oszkar , Seinfeld Joshua , Beauchamp Kathryn , Patel Vikas
Published: November 2008

The vast majority of pediatric lumbosacral spondylolisthesis have developmental etiology. Of the very rare type of pediatric lumbosacral facet dislocations, there are only three reported cases of a pediatric unilateral jumped facet injury. All of these cases are associated with fracture dislocation of L5-S1. Hyperflexion with rotation is thought to provoke this uncommon type of spine injury.

The authors report the first pediatric patient reported in literature to date with a traumatic unilateral jumped facet at the lumbosacral joint without fracture. The presentation, surgical treatment, hospital course, outcome and management options with the review of the literature is summarized.
Human Epidermal Growth Factor Receptor 2 Overexpression As a Prognostic Factor in a Large Tissue Microarray Series of Node-Negative Breast Cancers
Authors: Chia Stephen , Norris Brian , Speers Caroline , Cheang Maggie , Gilks Blake , Gown Allen M. , Huntsman David , Olivotto Ivo A. , Nielsen Torsten O. , Gelmon Karen
Published: November 2008

Purpose

Human epidermal growth factor receptor 2 gene (HER2) is associated with a poorer outcome in node-positive breast cancer, but the results are conflicting in node-negative disease. This study assessed the prognostic impact of HER2 overexpression/amplification in a large series of node-negative breast cancers.

Patients and Methods

A tissue microarray (TMA) series was constructed consisting of 4,444 invasive breast cancers diagnosed in British Columbia from 1986 to 1992. Within this series, 2,026 patients were node negative, of whom 70% did not receive adjuvant systemic therapy. The TMA series was assessed for estrogen receptor (ER) and HER2. Logistic regression modeling was used to estimate odds ratios at the 10-year follow-up.

Results

HER2 was positive in 10.2% of the node-negative cohort. In this cohort, an inferior outcome was seen in patients with HER2-positive tumors compared with HER2-negative tumors for 10-year relapse-free survival (RFS; 65.9% v 75.5%, respectively; P = .01), distant RFS (71.2% v 81.8%, respectively; P = .004), and breast cancer–specific survival (BCSS; 75.5% v 86.3%, respectively; P = .001). A trend for a worse overall survival was also seen (P = .06). HER2 was an independent poor prognostic factor for RFS and BCSS at 10 years, with odds ratios of 1.71 (P = .01) and 2.03 (P = .003), respectively. The number of HER2-positive tumors that were ≤ 1 cm was small, but there was a trend for a worse outcome in T1b tumors.

Conclusion

HER2 overexpression/amplification is correlated with a poorer outcome in node-negative breast cancer. Larger studies are needed to more clearly define the prognostic impact of HER2 in tumors ≤ 1 cm, particularly within the separate hormone receptor subgroups.
Comparison of Prospective and Retrospective Indicators of the Quality of End-of-Life Cancer Care
Authors: Setoguchi Soko , Earle Craig C. , Glynn Robert , Stedman Margaret , Polinski Jennifer M. , Corcoran Colleen P. , Haas Jennifer S.
Published: November 2008

Purpose

To compare prospectively and retrospectively defined benchmarks for the quality of end-of-life care, including a novel indicator for the use of opiate analgesia.

Methods

Linked claims and cancer registry data from 1994 to 2003 for New Jersey and Pennsylvania were used to examine prospective and retrospective benchmarks for seniors with breast, colorectal, lung, or prostate cancer who participated in state pharmaceutical benefit programs.

Results

Use of opiates, particularly long-acting opiates, was low in both the prospective and retrospective cohorts (9.1% and 10.1%, respectively), which supported the underuse of palliative care at the end-of-life. Although hospice was used more commonly in the retrospective versus prospective cohort, admission to hospice within 3 days of death was similar in both cohorts (28.8% v 26.4%), as was the rate of death in an acute care hospital. Retrospective and prospective measures identified similar physician and hospital patterns of end-of-life care. In multivariate models, a visit with an oncologist was positively associated with the use of chemotherapy, opiates, and hospice. Patients who were cared for by oncologists in small group practices were more likely to receive chemotherapy (retrospective only) and less likely to receive hospice (both) than those in large groups. Compared with patients who were cared for in teaching hospitals, those in other hospitals were more likely to receive chemotherapy (both) and to have toxicity (prospective) but were less likely to receive opiates (both) and hospice (retrospective).

Conclusion

Retrospective and prospective measures, including a new measure of the use of opiate analgesia, identify some similar physician and hospital patterns of end-of-life care.
Lymphedema and Quality of Life in Breast Cancer Survivors: The Iowa Women's Health Study
Authors: Ahmed Rehana L. , Prizment Anna , Lazovich DeAnn , Schmitz Kathryn H. , Folsom Aaron R.
Published: November 2008

Purpose

The impact of lymphedema or related arm symptoms on health-related quality of life (HRQOL) in breast cancer (BrCa) survivors has not been examined using a large population-based cohort.

Patients and Methods

The Iowa Women's Health Study (IWHS) collected self-report data for lymphedema, arm symptoms, and HRQOL (Medical Outcomes Study Short Form-36) in 2004 and data for cancer diagnosis, treatment, and behavioral and health characteristics between 1986 and 2003. We studied 1,287 women, age 55 to 69 years at baseline, who developed unilateral BrCa. We used cross-sectional analyses to describe the prevalence of lymphedema and arm symptoms and multivariate-adjusted generalized linear models to compare HRQOL (physical functioning, bodily pain, general health, physical and emotional role limitations, vitality, social functioning, and mental health) between the following three survivor groups: women with lymphedema (n = 104), women with arm symptoms without diagnosed lymphedema (n = 475), and women without lymphedema or arm symptoms (n = 708).

Results

The mean (± SE) time between BrCa diagnosis and lymphedema survey was 8.1 ± 0.2 years. Of BrCa survivors, 8.1% self-reported diagnosed lymphedema, and 37.2% self-reported arm symptoms. Knowledge of lymphedema was low among survivors without diagnosed lymphedema (n = 1,183). After multivariate adjustment, women with diagnosed lymphedema or arm symptoms without diagnosed lymphedema had lower physical and mental HRQOL compared with women without lymphedema or arm symptoms. Effect sizes were mild to moderate. There was a dose-response relation between number of arm symptoms and lower HRQOL.

Conclusion

In the IWHS, HRQOL was lower for BrCa survivors with diagnosed lymphedema and for those with arm symptoms without diagnosed lymphedema. Clinical trials are needed to determine what interventions can improve lymphedema and impact HRQOL for BrCa survivors.
Association of Serum Interleukin-7 Levels With the Development of Acute Graft-Versus-Host Disease
Authors: Dean Robert M. , Fry Terry , Mackall Crystal , Steinberg Seth M. , Hakim Fran , Fowler Daniel , Odom Jeanne , Foley Jason , Gress Ronald , Bishop Michael R.
Published: November 2008

Purpose

Morbidity from acute graft-versus-host disease (GVHD) limits the success of allogeneic hematopoietic stem-cell transplantation (HSCT) to treat malignancy. Interleukin-7 (IL-7), the principal homeostatic cytokine for T cells, is required for acute GVHD in murine models. In contrast to inflammatory cytokines (eg, IL-2, tumor necrosis factor α), IL-7 has not been studied extensively in the clinical transplant setting relative to its relationship with acute GVHD.

Patients and Methods

We evaluated the association of serum IL-7 levels with acute GVHD in 31 patients who were uniformly treated in a prospective clinical trial with reduced-intensity allogeneic HSCT from human leukocyte antigen–identical siblings. GVHD prophylaxis consisted of cyclosporine and methotrexate. Serum IL-7 levels and lymphocyte populations were determined at enrollment, the day of transplantation before the allograft infusion, and at specified intervals through 12 months post-transplantation.

Results

As expected, IL-7 levels were inversely correlated with T-cell populations (P < .00001). Acute GVHD was significantly associated with higher IL-7 levels at day +7 (P = .01) and day +14 (P = .00003) post-transplantation as well as with the allograft CD34+cell dose (P = .01). IL-7 levels at day +14 also correlated with the severity of acute GVHD (P < .0001). In logistic regression models, these factors were highly sensitive (up to 86%) and specific (100%) for classifying whether patients developed acute GVHD.

Conclusion

These data support preclinical observations that IL-7 plays a critical role in inducing acute GVHD and provide a rational basis for novel approaches to prevent and treat acute GVHD through modulation of the IL-7 pathway.
Phase III Trial Comparing Concurrent Biochemotherapy With Cisplatin, Vinblastine, Dacarbazine, Interleukin-2, and Interferon Alfa-2b With Cisplatin, Vinblastine, and Dacarbazine Alone in Patients With Metastatic Malignant Melanoma (E3695): A Trial Coordinated by the Eastern Cooperative Oncology Group
Authors: Atkins Michael B. , Hsu Jessie , Lee Sandra , Cohen Gary I. , Flaherty Lawrence E. , Sosman Jeffrey A. , Sondak Vernon K. , Kirkwood John M.
Published: November 2008

Purpose

Phase II trials with biochemotherapy (BCT) have shown encouraging response rates in metastatic melanoma, and meta-analyses and one phase III trial have suggested a survival benefit. In an effort to determine the relative efficacy of BCT compared with chemotherapy alone, a phase III trial was performed within the United States Intergroup.

Patients and Methods

Patients were randomly assigned to receive cisplatin, vinblastine, and dacarbazine (CVD) either alone or concurrent with interleukin-2 and interferon alfa-2b (BCT). Treatment cycles were repeated at 21-day intervals for a maximum of four cycles. Tumor response was assessed after cycles 2 and 4, then every 3 months.

Results

Four hundred fifteen patients were enrolled, and 395 patients (CVD, n = 195; BCT, n = 200) were deemed eligible and assessable. The two study arms were well balanced for stratification factors and other prognostic factors. Response rate was 19.5% for BCT and 13.8% for CVD (P = .140). Median progression-free survival was significantly longer for BCT than for CVD (4.8 v 2.9 months; P = .015), although this did not translate into an advantage in either median overall survival (9.0 v 8.7 months) or the percentage of patients alive at 1 year (41% v 36.9%). More patients experienced grade 3 or worse toxic events with BCT than CVD (95% v 73%; P = .001).

Conclusion

Although BCT produced slightly higher response rates and longer median progression-free survival than CVD alone, this was not associated with either improved overall survival or durable responses. Considering the extra toxicity and complexity, this concurrent BCT regimen cannot be recommended for patients with metastatic melanoma.
Phase III Study of Cisplatin, Etoposide, and Concurrent Chest Radiation With or Without Consolidation Docetaxel in Patients With Inoperable Stage III Non–Small-Cell Lung Cancer: The Hoosier Oncology Group and U.S. Oncology
Authors: Hanna Nasser , Neubauer Marcus , Yiannoutsos Constantin , McGarry Ronald , Arseneau James , Ansari Rafat , Reynolds Craig , Govindan Ramaswamy , Melnyk Anton , Fisher William , Richards Donald , Bruetman Daniel , Anderson Thomas , Chowhan Naveed , Nattam Sreenivasa , Mantravadi Prasad , Johnson Cynthia , Breen Tim , White Angela , Einhorn Lawrence
Published: November 2008

Purpose

Concurrent chemoradiotherapy is standard treatment for patients with inoperable stage III non–small-cell lung cancer (NSCLC). A phase II study by the Southwest Oncology Group using consolidation docetaxel after cisplatin (P), etoposide (E), and radiation (XRT) resulted in a median survival time (MST) of 26 months. This randomized phase III trial evaluated whether consolidation docetaxel was responsible for this improved survival.

Patients and Methods

Eligible patients had stage IIIA or IIIB NSCLC, baseline performance status of 0 to 1, forced expiratory volume in 1 second ≥ 1 L, and less than 5% weight loss. Patients received P 50 mg/m2 intravenously (IV) on days 1, 8, 29, and 36 and E 50 mg/m2 IV on days 1-5 and 29-33 concurrently with chest XRT to 59.40 Gy. Patients who did not experience progression were randomly assigned to docetaxel 75 mg/m2 IV every 21 days for three cycles versus observation. The primary end point was to compare overall survival (Kaplan-Meier analysis).

Results

On the basis of evidence of futility, a data and safety monitoring board recommended early termination after an analysis of the initial 203 patients. Patient characteristics (n = 203) were as follows: 34% female; median age, 63 years; 39.4% stage IIIA; and 60.6% stage IIIB. One hundred forty-seven (72.4%) of 203 patients were randomly assigned to docetaxel (n = 73) or observation (n = 74). Grade 3 to 5 toxicities during docetaxel included febrile neutropenia (10.9%) and pneumonitis (9.6%); 28.8% of patients were hospitalized during docetaxel (v 8.1% in observation arm), and 5.5% died as a result of docetaxel. The MST for all patients (n = 203) was 21.7 months; MST was 21.2 months for docetaxel arm compared with 23.2 months for observation arm (P = .883).

Conclusion

Consolidation docetaxel after PE/XRT results in increased toxicities but does not further improve survival compared with PE/XRT alone in patients with stage III inoperable NSCLC.
Physicians’ Experiences With BRCA1/2 Testing in Community Settings
Authors: Keating Nancy L. , Stoeckert Kathryn A. , Regan Meredith M. , DiGianni Lisa , Garber Judy E.
Published: November 2008

Purpose

We surveyed a national sample of nonacademic physicians who ordered BRCA1/2 testing to understand their implementation of genetic testing and to assess recommendations for surveillance and cancer risk management of women with positive test results.

Patients and Methods

We surveyed physicians (N = 611 of 1,050; response rate, 58.2%) practicing in nonacademic settings who ordered BRCA1/2 testing during 2004 to 2005. We described physicians’ experiences with testing and used multivariable regression models to identify factors associated with more complete counseling and with recommendations for cancer risk management for a BRCA1 mutation carrier.

Results

Most physicians (68.2%) usually or always discussed six counseling items before testing. In adjusted analyses, physicians who were assisted by genetic counselors, nurse geneticists, or others (v counseling by themselves), those who spent more than 60 minutes in counseling, and medical oncologists (v surgeons or geneticists) were more likely to discuss all six items (all P < .05). A total of 61.4% of physicians would recommend bilateral prophylactic mastectomy to a 38-year-old BRCA1 mutation carrier who had completed childbearing. After adjustment, geneticists and gynecologists were less likely than medical oncologists and surgeons to recommend prophylactic mastectomy (P < .001), as were physicians in the Northeast versus those in other regions of the United States (P = .01).

Conclusion

Community-based physicians seem to be successfully incorporating BRCA1/2 testing into their practices. Physicians’ recommendations for surveillance of mutation carriers are generally consistent with practice guidelines, yet recommendations for preference-based procedures such as prophylactic mastectomy vary by physician characteristics such as specialty and geographic region. The providers whom patients see for testing may contribute to variations in prophylactic treatments.
A mathematical model in three-dimensional piezoelectric continuum to predict non-linear responses of piezoceramic materials
Authors: Samal M K , Seshu P , von Wagner U , Hagedorn P , Dutta B K , Kushwaha H S
Published: November 2008

It has been experimentally observed that the piezoceramic materials exhibit different types of non-linearities under different combinations of electrical and mechanical fields. When excited near resonance in the presence of weak electric fields, they exhibit typical non-linearities similar to a Duffing oscillator such as jump phenomena and the presence of superharmonics in the response spectra. In this work, these non-linearities have been modelled for a generalized three-dimensional piezoelectric continuum using higher-order quadratic and cubic terms in the electric enthalpy density function and the virtual work. The identification of the parameters of the model requires a closed form solution for non-linear response of a simplified geometry. A simple proportional damping formulation has been used in the model. Experiments have been conducted on rectangular and cylindrical geometries of piezoceramic PIC 181 at different magnitudes of applied electric fields and results have been compared with those of simulation.
Finding the jerk properties of multi-body systems using helicoidal vector fields
Authors: Gallardo-Alvarado J , Orozco-Mendoza H , Rodríguez-Castro R
Published: November 2008

In this contribution, the kinematic angular and linear third-order properties, also known as jerk analysis, of a multi-body system are determined applying the concept of helicoidal vector fields. The reduced acceleration state, or accelerator, of the body of interest, with respect to a reference frame, is obtained as the time derivative, via a helicoidal field, of the velocity state, also known as the infinitesimal twist. Following that trend, the reduced jerk state, or jerkor, is obtained as the time derivative of the accelerator. The computation of the instantaneous centre of jerk, with its corresponding ellipsoid of jerk, is also included. The expressions thus obtained are extended systematically to multi-body systems. Two numerical examples are provided in order to illustrate the potential of the presented method.
Tribology of rough ultra-film contacts in drug delivery devices
Authors: Grimble D W , Theodossiades S , Rahnejat H , Wilby M
Published: November 2008

Elastomeric seals are extensively used in an assortment of drug delivery devices, such as syringes and pressurized metered dose inhalers. Although tribology of rubber seals and o-rings is reasonably well understood in engineering applications, the drug mixtures and formulations do not enjoy the required rheology to ensure coherent hydrodynamic action. In fact formation of uninterrupted hydrodynamic films is not actually sought in drug delivery devices, which often contain mixtures that are volatile when exposed to the environment. Furthermore, while engineering devices are often driven to overcome friction, many drug delivery systems are actuated manually and frequently by frail individuals. Therefore, the tribological problem is quite complex with many biological and environmental constraints. This paper highlights a parametric friction model for combined adhesive friction due to asperity interactions and non-Newtonian viscous action of the formulation. The model predicts the hysteretic behaviour of elastomeric seal contacts and conforms reasonably well to the experimental measurements of the same through actuation and release of inhaler valves.
A non-linear model for the atomization of a swirling viscous liquid jet
Authors: Ibrahim E A , Williams T L
Published: November 2008

The instability and consequent atomization of a swirling viscous liquid jet emanated into gaseous surroundings and subjected to periodical surface disturbances is modelled and investigated. The theoretical analysis is based on a simplified mathematical formulation of the continuity and momentum equations in their conservative forms. Numerical solutions of the governing equations along with appropriate initial and boundary conditions are obtained through a robust finite-difference scheme. The computations yield real-time evolution of the interfacial profile and subsequent breakup characteristics of the liquid jet. It is found that the jet disintegrates into main and satellite drops, under all the conditions considered in the present study. The swirl enhances the instability of the jet and causes radial stretching of the main drops, whereas the satellite drops exhibit axial elongation. Increasing viscosity hinders jet instability and leads to main and satellite drop deformations that are similar to those produced by the swirl. The sizes of both main and satellite drops are diminished at higher disturbance wave numbers. A greater swirl strength induces a higher dominant wave number, and hence a reduced size of resultant main and satellite drops. Larger satellite drops and smaller main drops are produced as viscous forces are increased. The present model could be used as a guide for designing swirl injectors.