bluuebunny/crossref_metadata_2025 huggingface dataset:
Wild leafy vegetables: A study of their subsistence dietetic support to the inhabitants of Nanda Devi Biosphere Reserve, India
Authors: Misra Shalini , Maikhuri RK , Kala CP , Rao KS , Saxena KG
Published: May 2008

Consumption of greens is a major source of vitamins and micro-nutrients for people using only vegetarian diets rich in carbohydrates. In remote rural settlements where vegetable cultivation is not practiced and market supplies are not organized, local inhabitants depend on indigenous vegetables, both cultivated in kitchen gardens and wild, for enriching the diversity of food. Knowledge of such foods is part of traditional knowledge which is largely transmitted through participation of individuals of households. A total of 123 households in six villages of Nanda Devi Biosphere Reserve buffer zone was surveyed using a schedule to assess the knowledge, availability and consumption pattern of wild leafy vegetables. Quantity estimations were done using regular visits with informants from 30 sample households of the six study villages during the collections. Monetization was used to see the value of wild leafy vegetables harvested during a year. The diversity of wild leafy vegetables being use by the local inhabitants is 21 species belonging to 14 genera and 11 families. This is far less than that being reported to be used by the communities from Western Ghats in India and some parts of Africa. Irrespective of social or economic status all households in the study villages had the knowledge and used wild leafy vegetables. The number of households reported to consume these wild leafy vegetables is greater than the number of households reporting to harvest them for all species except for Diplazium esculentum and Phytolacca acinosa. The availability and use period varied for the species are listed by the users. The study indicated that the knowledge is eroding due to changing social values and non participation of younger generation in collection and processing of such wild leafy vegetables.
Emergency room surgical workload in an inner city UK teaching hospital
Authors: Mai-Phan Tuong A , Patel Bijendra , Walsh Michael , Abraham Ajit T , Kocher Hemant M
Published: May 2008

Background

Emergency admissions may account for over 50% of surgical admissions. The impact on service provision and implications for training are difficult to quantify. We performed a cohort study to analyse these workload patterns.

Methods

Data on emergency room (ER) surgical admissions over six months was collected including patient demographics, referral sources, diagnosis, operation and length of stay and analysed according to sub-speciality and age-groups.

Results

There were 1392 (median age 41 (IQR 28–60) years, M:F = 1.7:1) emergency surgical admissions over six months; 45% were under 40 years of age and 48% patients self-referred to the ER. The commonest diagnoses were abscesses (11%), non-specific abdominal pain (9.7%) and neuro-trauma (9.6%). The median length of stay was 4 (IQR 2–8) days; with older (>80 years) patient staying significantly longer than those <40 years of age (median 8 vs 2 two days, P < 0.0001, Kruskal-Wallis test). Vascular patients remained in hospital longer than trauma or general surgery patients (median 14 vs 3 days, P < 0.0001, Kruskal-Wallis test). A high proportion (43.5%) of the patients required operative intervention and service implications of various diagnoses and operative interventions are highlighted.

Conclusion

With the introduction of shortened training period in Europe and World over, trainees may benefit from increased exposure to trauma and surgical emergencies. Resource planning should be based on more comprehensive, prospective data such as these.
Cigarette smoking associates with body weight and muscle mass of patients with rheumatoid arthritis: a cross-sectional, observational study
Authors: Stavropoulos-Kalinoglou Antonios , Metsios Giorgos S , Panoulas Vasileios F , Douglas Karen MJ , Nevill Alan M , Jamurtas Athanasios Z , Kita Marina , Koutedakis Yiannis , Kitas George D
Published: May 2008

Introduction

Rheumatoid arthritis (RA) is associated with altered metabolism leading to muscle wasting. In the general population, cigarette smoking is known to affect body composition by reducing fat and inhibiting muscle synthesis. Even though smoking has been implicated in the pathophysiology and progression of RA, its possible effects on body composition of such patients have not been studied. This cross-sectional study aimed to identify potential associations of smoking with body weight and composition of RA patients.

Methods

A total of 392 patients (290 females) with RA were assessed for body mass index (BMI), body fat (BF), fat-free mass (FFM), and waist circumference. Erythrocyte sedimentation rate, C-reactive protein, Disease Activity Score-28, and Health Assessment Questionnaire score were used to assess disease activity and severity. Smoking habit (current smoker, ex-smoker, or never-smoker) and intensity (pack-years) were also noted.

Results

Current smokers had a significantly lower BMI compared with ex-smokers (mean difference: male -2.6, 95% confidence interval [CI]: -3.5 to -1.7; female: -2.6, 95% CI: -4.8 to -0.5) and never-smokers (mean difference: male -1.8, 95% CI: -3 to -0.6; female: -1.4, 95% CI: -2.4 to -0.4). Similarly, the BF of current smokers was lower compared with that of ex-smokers (mean difference: male: -4.3, 95% CI: -7.5 to -1.2; female: -3.4, 95% CI: -6.4 to -0.4) and never-smokers (mean difference: male: -3.3, 95% CI: -6.3 to -0.4; female: -2.1, 95% CI: -4 to -0.2). FFM did not differ between groups. Finally, current smokers had a significantly smaller waist circumference compared with ex-smokers only (mean difference: male: -6.2, 95% CI: -10.4 to -1.9; female: -7.8, 95% CI: -13.5 to -2.1). Following adjustments for age, disease duration, and HAQ score, smoking remained a significant predictor for BMI (P < 0.001), BF (P < 0.05), and waist circumference (P < 0.05). Pack-years were inversely correlated with BF (r = -0.46; P < 0.001), and heavy smokers exhibited a significantly lower FFM (P < 0.05) compared with all other participants.

Conclusion

Within the limitations of a cross-sectional study, it appears that cigarette smoking associates with reduced BMI and BF in patients with RA and heavy smoking associates with lower muscle mass. Smoking cessation appears to associate with increased BMI, BF, and waist circumference in these patients. These results should be confirmed in prospective studies. Given the numerous adverse effects of smoking on general health and RA, patients should be actively advised against it. However, smoking cessation regimes in RA may need to include more general lifestyle counselling, particularly about weight control.
The scavenger receptor SR-A I/II (CD204) signals via the receptor tyrosine kinase Mertk during apoptotic cell uptake by murine macrophages
Authors: Todt Jill C , Hu Bin , Curtis Jeffrey L
Published: May 2008

Apoptotic cells (AC) must be cleared by macrophages (Mø) to resolve inflammation effectively. Mertk and scavenger receptor A (SR-A) are two of many receptors involved in AC clearance. As SR-A lacks enzymatic activity or evident intracellular signaling motifs, yet seems to signal in some cell types, we hypothesized that SR-A signals via Mer receptor tyrosine kinase (Mertk), which contains a multisubstrate docking site. We induced apoptosis in murine thymocytes by dexamethasone and used Western blotting and immunoprecipitation to analyze the interaction of Mertk and SR-A in the J774A.1 (J774) murine Mø cell line and in peritoneal Mø of wild-type mice and SR-A−/− mice. Phagocytosis (but not adhesion) of AC by J774 was inhibited by anti-SR-A or function-blocking SR-A ligands. In resting J774, SR-A was associated minimally with unphosphorylated (monomeric) Mertk; exposure to AC induced a time-dependent increase in association of SR-A with Mertk in a direct or indirect manner. Anti-SR-A inhibited AC-induced phosphorylation of Mertk and of phospholipase Cγ2, essential steps in AC ingestion. Relative to tissue Mø of wild-type mice, AC-induced Mertk phosphorylation was reduced and delayed in tissue Mø of SR-A−/− mice, as was in vitro AC ingestion at early time-points. Thus, during AC uptake by murine Mø, SR-A is essential for optimal phosphorylation of Mertk and subsequent signaling required for AC ingestion. These data support the Mertk/SR-A complex as a potential target to manipulate AC clearance and hence, resolution of inflammation and infections.
Sexual dysfunction and schizophrenia: psychiatrists' attitudes and training needs
Authors: Nnaji Romanus Ndubueze , Friedman Trevor
Published: May 2008

Aims and Method

We conducted a survey of the knowledge, attitudes and practices of sexual dysfunction and schizophrenia of general adult psychiatrists in Leicestershire and Lincolnshire mental health trusts.

Results

Two-thirds of psychiatrists that we interviewed do not routinely enquire about sexual dysfunction in their patients and only 17% felt competent in assessing sexual dysfunction, despite 88% agreeing that good sexual function is important to patients. Most practitioners (81.6%) have had no training in this area and wanted some.

Clinical Implications

Sexual dysfunction is underrecognised and possibly under-treated; suggestions on how to address this are made in this paper.
Daytime night attire as a therapeutic intervention in an acute adult psychiatric in-patient unit
Authors: Langan Camilla , McDonald Colm
Published: May 2008

Aims and Method

Dressing in-patients in night attire during daytime is currently practised in many in-patient psychiatric units, despite the lack of evidence to support its benefit in reducing absconding or self-harm. Using a triangulation design, we investigated the prevalence of, attitudes towards and associations of this practice in an acute psychiatric in-patient setting in the Republic of Ireland.

Results

Case-note review revealed a high prevalence of this practice (57%) and its significant association with involuntary admission. Nursing staff believed that using night attire was effective at reducing absconding and self-harm, and that only voluntary patients should retain the right to choose their clothes. Most patients interviewed were uncomfortable in night clothes and indicated that they should be entitled to choose what to wear.

Clinical Implications

Night attire is regularly used for risk-management, despite lack of evidence supporting its efficacy and negative attitudes towards it in many patients. This practice and the reasons for its implementation deserve medical documentation.
Mentoring: views and experiences of psychiatrists from low- and middle-income, and high-income countries
Authors: Khan Sobia T. , Khan Faria , Chaudary Haroon Rashid
Published: May 2008

Aims and Method

A cross-sectional qualitative survey was undertaken to compare the views and experiences of psychiatrists working in low- and middle-income, and high-income countries. Questionnaires were distributed to 110 psychiatrists attending the 2007 World Psychiatric Conference in Lahore, Pakistan.

Results

Of the 110 psychiatrists from 13 countries, 81 were included in the analysis. Their views and experiences on mentoring were compared according to country of practice, age, gender, sub-specialty and grade. No significant differences were found on any of the variables studied.

Clinical Implications

Mentoring relationship, identified as an appropriate means of responding to personal and professional challenges of psychiatric practice is valued by psychiatrists regardless of the country they have had their practice in. Our findings warrant wider study.
Isolation, Cloning, and Expression Mapping of a Gene Encoding an Antidiuretic Hormone and Other CAPA-Related Peptides in the Disease Vector, Rhodnius prolixus
Authors: Paluzzi Jean-Paul , Russell William K. , Nachman Ronald J. , Orchard Ian
Published: May 2008

After a blood meal, Rhodnius prolixus undergoes a rapid diuresis to eliminate excess water and salts. During the voiding of this primary urine, R. prolixus acts as a vector of Chagas’ disease, with the causative agent, Trypanosoma cruzi, infecting the human host via the urine. Diuresis in R. prolixus is under the neurohormonal control of serotonin and peptidergic diuretic hormones, and thus, diuretic hormones play an important role in the transmission of Chagas’ disease. Although diuretic hormones may be degraded or excreted, resulting in the termination of diuresis, it would also seem appropriate, given the high rates of secretion, that a potent antidiuretic factor could be present and act to prevent excessive loss of water and salts after the postgorging diuresis. Despite the medical importance of R. prolixus, no genes for any neuropeptides have been cloned, including obviously, those that control diuresis. Here, using molecular biology in combination with matrix-assisted laser desorption ionization-time of flight-tandem mass spectrometry, we determined the sequence of the CAPA gene and CAPA-related peptides in R. prolixus, which includes a peptide with anti-diuretic activity. We have characterized the expression of mRNA encoding these peptides in various developmental stage and also examined the tissue-specific distribution in fifth-instars. The expression is localized to numerous bilaterally paired cell bodies within the central nervous system. In addition, our results show that RhoprCAPA gene expression is also associated with the testes, suggesting a novel role for this family of peptides in reproduction.
Structural Interactions between Kisspeptin and GnRH Neurons in the Mediobasal Hypothalamus of the Male Rhesus Monkey (Macaca mulatta) as Revealed by Double Immunofluorescence and Confocal Microscopy
Authors: Ramaswamy Suresh , Guerriero Kathryn A. , Gibbs Robert B. , Plant Tony M.
Published: May 2008

Kisspeptin is recognized to play a critical role in eliciting the pubertal resurgence of pulsatile GnRH release, the proximal trigger of puberty in higher primates. Expression of the kisspeptin receptor (GPR54) by GnRH neurons indicates a direct action of kisspeptin on the GnRH neuronal network. The purpose of the present study was to examine the distribution of kisspeptin cell bodies in the monkey hypothalamus and to assess the structural basis for the stimulatory action of kisspeptin on the GnRH neuronal network. Three castrated male rhesus monkeys, 39–51 months of age, were deeply anesthetized and their brains perfused transcardially with 4% paraformaldehyde in PBS. Serial 25-μm coronal sections throughout the hypothalamus were prepared, and immunopositive neurons identified using a cocktail of specific primary antibodies (sheep anti-kisspeptin at 1:120,000, and rabbit anti-GnRH at 1:100,000) detected with fluorescently tagged secondary antibodies (antisheep, Alexa Fluor 488; antirabbit, Cy3) in combination with confocal microscopy. Kisspeptin perikarya were found only in the mediobasal hypothalamus (MBH) almost exclusively in the posterior two-thirds of the arcuate nucleus. Surprisingly, kisspeptin-beaded axons made only infrequent contacts with GnRH neurons (kisspeptin and GnRH profiles abutting in a 0.5- to 1.0-μm optical section) in the MBH. In the median eminence, kisspeptin and GnRH axons were found in extensive and intimate association. GnRH contacts on kisspeptin perikarya and dendrites were observed. These findings indicate that nonsynaptic pathways of communication in the median eminence should be considered as a possible mechanism of kisspeptin regulation of GnRH release, and provide an anatomical basis for reciprocal control of kisspeptin neuronal activity by GnRH.
Lessons Learned from the 1994 Rwanda Genocide
Authors: Murigande Charles
Published: May 2008

Charles Murigande is minister of foreign affairs and cooperation of the Republic of Rwanda. This essay is adapted from a presentation to the Congressional Black Caucus, Washington, DC, 21 September 2007.
Hydrodynamic performance of the minke whale (Balaenoptera acutorostrata) flipper
Authors: Cooper Lisa Noelle , Sedano Nils , Johansson Stig , May Bryan , Brown Joey D. , Holliday Casey M. , Kot Brian W. , Fish Frank E.
Published: May 2008

Minke whales (Balaenoptera acutorostrata) are the smallest member of balaenopterid whales and little is known of their kinematics during feeding maneuvers. These whales have narrow and elongated flippers that are small relative to body size compared to related species such as right and gray whales. No experimental studies have addressed the hydrodynamic properties of minke whale flippers and their functional role during feeding maneuvers. This study integrated wind tunnel, locomotion and anatomical range of motion data to identify functional parameters of the cambered minke whale flipper. A full-sized cast of a minke whale flipper was used in wind tunnel testing of lift, drag and stall behavior at six speeds, corresponding to swimming speeds of 0.7–8.9 m s–1. Flow over the model surface stalled between 10° and 14° angle of attack (α) depending on testing speed. When the leading edge was rotated ventrally, loss in lift occurred around –18° α regardless of speed. Range of mobility in the fresh limb was approximately 40% greater than the range of positive lift-generating angles of attack predicted by wind tunnel data (+14°α). Video footage, photographs and observations of swimming, engulfment feeding and gulping minke whales showed limb positions corresponding to low drag in wind tunnel tests, and were therefore hydrodynamically efficient. Flippers play an important role in orienting the body during feeding maneuvers as they maintain trim of the body, an action that counters drag-induced torque of the body during water and prey intake.
Nest-mark orientation versus vector navigation in desert ants
Authors: Bregy Patrick , Sommer Stefan , Wehner Rüdiger
Published: May 2008

Foraging ants and bees use path-integration vectors and landmark cues for navigation. When in particular experimental paradigms the two types of information – vector-based and landmark-based information – are made to compete with each other, the insect may weight either source more heavily depending on the navigational context and the animal's motivational state. Here we studied the effects of a displaced nest mark on the homing performances of Cataglyphis ants. Foragers were trained to shuttle between the nest, which was marked by a black cylinder (the beacon), and an artificial feeder. Trained ants were captured at the feeder and transferred to a distant test field, where they experienced the nest mark at various positions relative to their home vector. When the beacon was positioned to one side of the point of release, the ants slightly drifted towards the beacon right at the start of their inbound run, but thereafter resumed their home-vector courses. When the nest mark appeared to one side further down the homing course, the ants set off in the home-vector direction, but then gradually drifted towards the beacon. The distance, at which this occurred,and the ants' drift from the home-vector course were very similar across test conditions. During the final search for the nest, landmark information dominated the ants' path integrator. The results clearly show that nest-mark memories are effective during the entire vector-based homeward course, but that they are either only partly activated or partly used unless the state of the ants' path integrator is close to zero.
Stress, lies and red tape: the views, success rates and stress levels of the MTAS cohort
Authors: Whelan Paul , Meerten Maja , Rao Rahul , Jarrett Peter , Muthukumaraswamy Anandamurugan , Bhugra Dinesh
Published: May 2008

Summary

Objective

To track the success rates in obtaining a specialist training (ST) post of a cohort of medical training application system (MTAS) applicants, as well as canvassing their views of the process and measuring symptoms of psychological distress during application and after job allocation.

Design

A follow-up cross-sectional survey.

Setting

Two large south London psychiatry training schemes.

Participants

101 MTAS applicants.

Main outcome measures

Success in obtaining an ST post, respondents' views about MTAS and General Health Questionnaire-12 (GHQ-12) scores.

Results

48 of the original sample responded to the follow-up survey. Data were available about post-MTAS job status for a further 41 trainees. 64% of candidates obtained an ST post. Of those, however, 12% were only offered a fixed-term post. Most unsuccessful candidates were doing locum (34%) or non-training grade (21%) jobs. UK/European Economic Area (EEA) doctors were more successful than non-EEA applicants in obtaining an ST post (odds ratio 5.5, 95% confidence interval 2.1–14.3), as were women candidates compared to men (3.7, 0.5–9.3). The respondents' views about MTAS were globally negative (even if they were successful in obtaining an ST post). The median GHQ-12 score for respondents was 7 out of a potential total score of 12. 79% of the sample scored above the threshold (GHQ-12 ≥4) for psychological distress and 21% experienced significant distress (GHQ-12 ≥8).

Conclusions

MTAS was a flawed system. A considerable proportion (36%) of candidates who had been on a Senior House Officer training scheme were left without a training post after MTAS. The system seems to favour UK/EEA applicants. Applicants suffered significant psychological distress during and after the MTAS process.
Obesity and urinary incontinence
Authors: Khong Su-Yen , Jackson Simon
Published: May 2008

Obesity is growing at an alarming rate worldwide. It poses a major health problem that in turn places a huge financial burden on health services. Medical conditions such as diabetes mellitus and ischaemic heart disease are commonly associated with obesity but less well documented is the association between obesity and urinary incontinence. This article reviews the current literature to see whether: (1) obesity predisposes to urinary incontinence; (2) weight loss improves urinary incontinence and (3) obesity affects the surgical outcome. It also covers the surgical and anaesthetic implications of obesity. New minimally invasive surgical techniques make surgical risks acceptable for the obese patient but the anaesthetic risks remain high. Obese patients should not be denied surgery but be made aware of the higher risks. Future research should focus on the impact of obesity on surgical outcomes for continence surgery particularly on intraoperative and postoperative complication rates as well as long-term cure rates.
A 10-year follow-up of the effect of continuous-combined hormone replacement therapy and its discontinuation on bone in postmenopausal women
Authors: Heikkinen Jorma , Vaheri Raija , Haapalahti Jouko , Timonen Ulla
Published: May 2008

Objective

To establish the effect on bone mineral density (BMD) of long-term (nine years) continuous-combined hormone replacement therapy (ccHRT) with estradiol valerate/medroxyprogesterone acetate (E2V/MPA) and follow-up one year after discontinuation of ccHRT.

Study design

A total of 279 women were treated with daily dosages of E2V + MPA: 1 mg + 2.5 mg (n = 69), 1 mg + 5 mg (n = 70) or 2 mg + 5 mg (n = 140) (Indivina®, Orion Pharma, Espoo, Finland) for 8.5 years; all subjects received the lowest dosage for the next six months. BMD was measured at baseline, between 6 and 12 months, annually until the end of study and at one-year postdiscontinuation of ccHRT.

Main outcome measure

Change in BMD during nine years of treatment with ccHRT and at one-year post-discontinuation of ccHRT.

Results

Progressive increase of vertebral BMD was observed with all dosage regimens throughout nine years, with corresponding reduction in the proportion of women fulfilling criteria for osteoporosis or osteopaenia. Femoral neck BMD reached a peak at about five to six years, whereas in the lumbar spine the BMD increase was sustained until the end of the study treatment. Mean BMD declined after cessation of ccHRT use but remained substantially above baseline levels. In a subset of women (n = 58) there was a rapid (≤4%) loss of vertebral BMD in the year after termination of ccHRT use. These women had lower than average BMD at baseline but no other factor was identified that distinguished them from the overall study population.

Conclusions

Low-dose ccHRT in postmenopausal women is associated with increases in lumbar spine BMD for at least nine years. These gains are not sustained after cessation of therapy but the rate of BMD loss varies between individuals.
Direct Determination of Lipoprotein Particle Sizes and Concentrations by Ion Mobility Analysis
Authors: Caulfield Michael P , Li Shuguang , Lee Gloria , Blanche Patricia J , Salameh Wael A , Benner W Henry , Reitz Richard E , Krauss Ronald M
Published: May 2008

Background: Current methods for measuring the concentrations of lipoprotein particles and their distributions in particle subpopulations are not standardized. We describe here and validate a new gas-phase differential electrophoretic macromolecular mobility-based method (ion mobility, or IM) for direct quantification of lipoprotein particles, from small, dense HDL to large, buoyant, very-low-density lipoprotein (VLDL).

Methods: After an ultracentrifugation step to remove albumin, we determined the size and concentrations of lipoprotein particles in serum samples using IM. Scan time is 2 min and covers a particle range of 17.2–540.0 Å. After scanning, data are pooled by totaling the particle number across a predetermined size range that corresponds to particular lipoprotein subclasses. IM results were correlated with those of standard methods for cholesterol and apolipoprotein analysis.

Results: Intra- and interassay coefficients of variation for LDL particle size were <1.0%. The intra- and interassay variation for LDL and HDL particle subfraction measurements was <20%. IM-measured non-HDL correlated well with apolipoprotein B (r = 0.92).

Conclusions: The IM method provides accurate, reproducible, direct determination of size and concentration for a broad range of lipoprotein particles. Use of this methodology in studies of patients with cardiovascular disease and other pathologic states will permit testing of its clinical utility for risk assessment and management of these conditions.
Delayed Acclimatization of the Ventilatory Threshold in Healthy Trekkers
Authors: Myers Stephen D. , Biccard Bruce M. , Chan Colin , Imray Christopher H.E. , Wright Alexander D. , Pattinson Kyle T.S.
Published: May 2008

Objective

To test the hypothesis that acclimatization to high altitude results in an improvement of the ventilatory threshold (VT).

Methods

Eight lowlanders underwent cardiopulmonary exercise testing with a cycle ergometer to determine VT and peak oxygen uptake (Vo2peak) in Coventry, United Kingdom (altitude: 80 m), on arrival in Leh, India (altitude: 3500 m), and after 12 days of acclimatization that included a 5-day high altitude trek up to 4770 m.

Results

Vo2peak fell on arrival at 3500 m and remained depressed at 12 days. VT was depressed on arrival at high altitude and was further depressed at 12 days. VT as a proportion of the Vo2peak was decreased on arrival at high altitude, and after acclimatization, this relationship was further decreased.

Conclusions

Individuals who are sedentary or not participating in regular physical training appear to require a longer period of acclimatization than trained athletes. With the increasing numbers participating in high-altitude trekking and charity climbs of peaks, such as Mt. Kilimanjaro, this information has clinically significant practical implications for those leading or acting as medical advisors.
Characterization of a Novel Ubiquitin-Conjugating Enzyme That Regulates β1,4-Galactosyltransferase-1 in Embryonic Stem Cells
Authors: Wassler Michael J. , Shur Barry D. , Zhou Wenxia , Geng Yong-Jian
Published: May 2008

In this study we identified a novel galactosyltransferase 1-associating protein (GTAP) by cDNA cloning from a murine embryonic cDNA library using the two-hybrid yeast system. GTAP is expressed in early embryonic tissues, as well as in adult tissues with active cell turnover, and belongs to the class III ubiquitin-conjugating (E2) enzyme family. Its COOH-terminal domain contains a consensus sequence for ubiquitin binding shared by all the ubiquitin-conjugating enzymes, whereas its NH2-terminal domain appears critical for the binding and internalization of cell surface galactosyltransferase 1 (GalT1) in embryonic stem cells through a monensin- and MG132-dependent pathway. We have found that GTAP regulates GalT1-associated, laminin-dependent embryonic cell adhesion and the formation of embryoid bodies. Thus, GTAP functions as an evolutionarily conserved E2 enzyme, which may participate in intercellular adhesion and embryonic development.

Disclosure of potential conflicts of interest is found at the end of this article.
Fate-Mapping Evidence That Hepatic Stellate Cells Are Epithelial Progenitors in Adult Mouse Livers
Authors: Yang Liu , Jung Youngmi , Omenetti Alessia , Witek Rafal P. , Choi Steve , Vandongen Hendrika M. , Huang Jiawen , Alpini Gianfranco D. , Diehl Anna Mae
Published: May 2008

Liver injury activates quiescent hepatic stellate cells (Q-HSC) to proliferative myofibroblasts. Accumulation of myofibroblastic hepatic stellate cells (MF-HSC) sometimes causes cirrhosis and liver failure. However, MF-HSC also promote liver regeneration by producing growth factors for oval cells, bipotent progenitors of hepatocytes and cholangiocytes. Genes that are expressed by primary hepatic stellate cell (HSC) isolates overlap those expressed by oval cells, and hepatocytic and ductular cells emerge when HSC are cultured under certain conditions. We evaluated the hypothesis that HSC are a type of oval cell and, thus, capable of generating hepatocytes to regenerate injured livers. Because Q-HSC express glial fibrillary acidic protein (GFAP), we crossed mice in which GFAP promoter elements regulated Cre-recombinase with ROSA-loxP-stop-loxP-green fluorescent protein (GFP) mice to generate GFAP-Cre/GFP double-transgenic mice. These mice were fed methionine choline-deficient, ethionine-supplemented diets to activate and expand HSC and oval cell populations. GFP(+) progeny of GFAP-expressing precursors were characterized by immunohistochemistry. Basal expression of mesenchymal markers was negligible in GFAP(+)Q-HSC. When activated by liver injury or culture, HSC downregulated expression of GFAP but remained GFP(+); they became highly proliferative and began to coexpress markers of mesenchyme and oval cells. These transitional cells disappeared as GFP-expressing hepatocytes emerged, began to express albumin, and eventually repopulated large areas of the hepatic parenchyma. Ductular cells also expressed GFAP and GFP, but their proliferative activity did not increase in this model. These findings suggest that HSC are a type of oval cell that transitions through a mesenchymal phase before differentiating into hepatocytes during liver regeneration.

Disclosure of potential conflicts of interest is found at the end of this article.
Improved Efficiency and Pace of Generating Induced Pluripotent Stem Cells from Human Adult and Fetal Fibroblasts
Authors: Mali Prashant , Ye Zhaohui , Hommond Holly H. , Yu Xiaobing , Lin Jeff , Chen Guibin , Zou Jizhong , Cheng Linzhao
Published: May 2008

It was reported recently that human fibroblasts can be reprogrammed into a pluripotent state that resembles that of human embryonic stem (hES) cells. This was achieved by ectopic expression of four genes followed by culture on mouse embryonic fibroblast (MEF) feeders under a condition favoring hES cell growth. However, the efficiency of generating human induced pluripotent stem (iPS) cells is low, especially for postnatal human fibroblasts. We started supplementing with an additional gene or bioactive molecules to increase the efficiency of generating iPS cells from human adult as well as fetal fibroblasts. We report here that adding SV40 large T antigen (T) to either set of the four reprogramming genes previously used enhanced the efficiency by 23–70-fold from both human adult and fetal fibroblasts. Discernible hES-like colonies also emerged 1–2 weeks earlier if T was added. With the improved efficiency, we succeeded in replacing MEFs with immortalized human feeder cells that we previously established for optimal hES cell growth. We further characterized individually picked hES-like colonies after expansion (up to 24 passages). The majority of them expressed various undifferentiated hES markers. Some but not all the hES-like clones can be induced to differentiate into the derivatives of the three embryonic germ layers in both teratoma formation and embryoid body (EB) formation assays. These pluripotent clones also differentiated into trophoblasts after EB formation or bone morphogenetic protein 4 induction as classic hES cells. Using this improved approach, we also generated hES-like cells from homozygous fibroblasts containing the sickle cell anemia mutation Hemoglobin Sickle.

Disclosure of potential conflicts of interest is found at the end of this article.
Use of Intravenous Bisphosphonates in Older Women with Breast Cancer
Authors: Giordano Sharon H. , Fang Shenying , Duan Zhigang , Kuo Yong-Fang , Hortobagyi Gabriel N. , Goodwin James S.
Published: May 2008

Learning Objectives

After completing this course, the reader will be able to: Make optimal use of i.v. bisphosphonates in women with breast cancer.Uphold the current guidelines for the use of bisphosphonates among women with metastatic breast cancer.Assess the relationship between bisphosphonate use and patient age.

CME This article is available for continuing medical education credit at CME.TheOncologist.com

Introduction.

i.v. bisphosphonates reduce skeletal events in women with bone metastases from breast cancer, but little is known about the prevalence and duration of bisphosphonate use.

Methods.

Patients were identified from the Surveillance, Epidemiology, and End Results–Medicare database who were aged ≥65 years and were diagnosed with invasive breast cancer in 1995–2002. Healthcare Common Procedure Coding System codes were used to identify patients treated with pamidronate and zoledronic acid. Descriptive statistics were used to describe patterns of use. Multivariate analyses were performed to determine the predictors of bisphosphonate use.

Results.

In total, 55,864 women with breast cancer were included, with 307,467 person-years of follow-up. Overall, 1.26% of women with all stages of breast cancer received i.v. bisphosphonates. In 2004, 2% of all breast cancer patients and 32% of patients with distant stage disease received bisphosphonates. Approximately two thirds of patients treated with bisphosphonates received zoledronic acid and one third received pamidronate in 2004. Multivariate analyses showed that patients who were ≥75 years old were less likely to receive bisphosphonates (75–79 years versus 65–69 years: odds ratio [OR], 0.81; 95% confidence interval [CI], 0.70–0.93; 80+ years versus 65–69 years: OR, 0.49; 95% CI, 0.42–0.57). The use of bisphosphonates dramatically increased over time. The majority of living patients were continued on i.v. bisphosphonates once started (83% at 1 year, 64% at 3 years, 50% at 5 years), but the median survival time after initiation of i.v. bisphosphonates was only 21 months.

Conclusions.

i.v. bisphosphonates appear to be underused in patients with metastatic breast cancer, particularly among those patients >75 years of age.
Integrated Analysis of Zoledronic Acid for Prevention of Aromatase Inhibitor–Associated Bone Loss in Postmenopausal Women with Early Breast Cancer Receiving Adjuvant Letrozole
Authors: Brufsky Adam , Bundred Nigel , Coleman Robert , Lambert-Falls Rosemary , Mena Raul , Hadji Peyman , Jin Lixian , Schenk Nora , Ericson Solveig , Perez Edith A.
Published: May 2008

Learning Objectives

After reading this article, the reader should be able to: Monitor for and treat to prevent bone loss in postmenopausal breast cancer patients receiving an aromatase inhibitor.Describe the methodology of the Z-FAST and ZO-FAST clinical trials.Discuss the effectiveness and tolerability of zoledronic acid when administrated to prevent bone loss associated with aromatase inhibitors.

CME This article is available for continuing medical education credit at CME.TheOncologist.com

Background.

The interim (12-month) results of two similarly designed, ongoing studies (the Zometa®-Femara® Adjuvant Synergy Trials [Z-FAST and ZO-FAST]) suggest that zoledronic acid (4 mg intravenously every 6 months) when initiated with adjuvant letrozole increases bone mineral density (BMD) of the lumbar spine (LS) in postmenopausal women with early-stage breast cancer compared with patients who receive zoledronic acid only when bone loss became clinically significant or a fragility fracture occurred.

Methods.

An integrated analysis was performed to maximize the value of the large pool of data from the two studies in answering clinically relevant questions. The primary objective was to compare the change in LS BMD at month 12. Secondary objectives included comparing (a) the change in total hip (TH) BMD, (b) changes in bone turnover marker concentrations, (c) time to disease recurrence, and (d) safety at month 12.

Findings.

The integrated analysis included 1,667 patients. At month 12, LS BMD was 5.2% higher in the upfront group than in the delayed group; TH BMD was 3.5% higher. N-telopeptide and bone-specific alkaline phosphatase concentrations decreased by 21.3% and 12.8% in the upfront group and increased by 21.7% and 24.9% in the delayed group, respectively (p < .0001 for intergroup comparisons). Fewer patients receiving upfront zoledronic acid experienced disease recurrence than patients in the delayed group—seven patients (0.84%) versus 17 patients (1.9%) (p = .0401). Fracture rates were similar. No confirmed osteonecrosis of the jaw was reported.

Conclusions.

The results of this analysis strengthen the statistical validity of the preliminary results of the Z-FAST and ZO-FAST studies, showing that upfront zoledronic acid prevents aromatase inhibitor–associated bone loss more effectively than delayed-start zoledronic acid in postmenopausal women with early-stage breast cancer receiving letrozole. Additionally, disease recurrence appears to be lower with upfront zoledronic acid, but further follow-up is needed to confirm these interim results.
Health Economic Evaluation of Treating Anemia in Cancer Patients Receiving Chemotherapy: A Study in Belgian Hospitals
Authors: Spaepen Erik , Demarteau Nadia , Van Belle Simon , Annemans Lieven
Published: May 2008

Background.

Erythropoiesis-stimulating agents (ESAs) are used in chemotherapy-induced anemia (CIA) with the goal of improving quality of life and preventing RBC transfusions. This retrospective database study compared the three currently available ESAs, epoetin alfa (EPO-A), epoetin beta (EPO-B), and darbepoetin alfa (DARB), regarding costs and outcomes.

Methods.

Data were obtained from a Belgian longitudinal database, including medical and financial data on cancer patients receiving chemotherapy and ESAs, submitted by 46 Belgian hospitals. Propensity score matching was applied to correct for selection bias. The main effectiveness parameter was defined as transfusion- and anemia-readmission-free survival (TA-free survival) at 3 months. Costs were analyzed taking the health care payer perspective.

Results.

Including 1,584 EPO-A, 380 EPO-B, and 429 DARB propensity-matched patients, TA-free survival rates were similar for the three groups (DARB, 84.37%; EPO-A, 84.60%; EPO-B, 84.94%). Overall inpatient costs were €16,949 ± €1,025, €19,472 ± €901, and €19,295 ± €1,048 for DARB, EPO-A, and EPO-B, respectively (DARB versus EPO-A, p < .0001 and DARB versus EPO-B, p = .008). Anemia-associated costs were €3,051 ± €218 in the DARB group, compared with €3,995 ± €144 for EPO-A (p < .0001) and €3,752 ± €229 for EPO-B (p = .0132).

Conclusion.

To our knowledge, this is the first real-life matched retrospective study comparing ESAs with regard to both costs and effects. For similar patient profiles, the patients in the DARB group consumed the smallest amounts of ESAs, with similar clinical outcomes. These data therefore suggest a greater efficiency of DARB in the treatment of CIA.
Current Management of Medullary Thyroid Cancer
Authors: Sippel Rebecca S. , Kunnimalaiyaan Muthusamy , Chen Herbert
Published: May 2008

Learning Objectives

After completing this course, the reader will be able to: Evaluate a patient with a new diagnosis of medullary thyroid cancer.Use genetic testing for the ret proto-oncogene and assess how the location of the mutation affects the risks for the patient.Select among the surgical treatment options for patients with medullary thyroid cancer, including the optimal surgical treatment for patients with palpable disease as well as those patients who are found to be genetic carriers.

CME This article is available for continuing medical education credit at CME.TheOncologist.com

Medullary thyroid cancer accounts for 5%–10% of all thyroid cancers. The majority of medullary thyroid cancers are sporadic, but 20% of cases are a result of a germline mutation in the ret proto-oncogene. Hereditary medullary thyroid cancer can be seen as part of the multiple endocrine neoplasia syndrome type 2A or 2B or as part of familial medullary thyroid cancer. This article discusses the current methods available for the diagnosis and evaluation of a patient with suspected medullary thyroid cancer. The management of medullary thyroid cancer is predominantly surgical excision, consisting of a total thyroidectomy and lymph node dissection. The extent and timing of surgical excision are discussed. Systemic therapeutic options are limited for medullary thyroid cancer, but several therapeutic targets show promise for the development of new therapies in the future.
The Forgotten Team Member: Meeting the Needs of Oncology Support Staff
Authors: Cashavelly Barbara J. , Donelan Karen , Binda Kathryn D. , Mailhot Johanna R. , Clair-Hayes Katherine A. , Maramaldi Peter
Published: May 2008

Learning Objectives

After completing this course, the reader will be able to: Assess the impact of oncology care on nonlicensed support staff.Identify four areas that challenge support staff caring for oncology patients.Evaluate the impact of burnout and job satisfaction on support staff caring for oncology patients.

CME This article is available for continuing medical education credit at CME.TheOncologist.com

Introduction.

The impact of working in an oncology setting has been widely researched for physicians, nurses, social workers, and chaplains. The experiences of nonlicensed support staff in an oncology setting have rarely been acknowledged or addressed. Few studies have addressed support or education initiatives for support staff caring for oncology patients. The intent of this study was to understand the work experiences of oncology support staff. Emotional impact, patient relationships, and team relationships were addressed. These data would help shape the development of an oncology support staff program.

Methods.

A qualitative and quantitative approach was used to explore the experiences of support staff. Seven focus groups and individual interviews were conducted addressing work life in a cancer center. The quantitative survey collected baseline data on job satisfaction, working relationships, patient relationships, burnout, and support programs.

Results.

Four predominant themes emerged from the focus groups. These included: relationships with patients and families, coping with death and dying, value and recognition, and balancing function with emotion. The quantitative survey reported the highest satisfaction with patient relationships and the lowest satisfaction with job recognition and supervisor support. High personal accomplishment scores declined with duration of employment. Educational grand rounds were a high interest.

Discussion.

This study provides insight into the impact of caring for oncology patients on support staff. Burnout and job satisfaction can be costly. Recognizing the challenges inherent in the oncology environment is essential to supporting a successful oncology practice for licensed and nonlicensed support staff.
EBV-Associated Lymphoproliferative Disorders: Classification and Treatment
Authors: Carbone Antonino , Gloghini Annunziata , Dotti Giampietro
Published: May 2008

Learning Objectives

After completing this course, the reader will be able to: Assess patients with EBV-associated lymphoproliferative disorders.Describe the pathogenesis of the lymphoproliferative disorders linked to EBV infection.Evaluate EBV cell–based immunotherapy for use in patients with EBV-associated lymphoproliferative disorders.

CME This article is available for continuing medical education credit at CME.TheOncologist.com

Since its discovery as the first human tumor virus, Epstein-Barr virus (EBV) has been implicated in the development of a wide range of B-cell lymphoproliferative disorders, including Burkitt's lymphoma, classic Hodgkin's lymphoma, and lymphomas arising in immunocompromised individuals (post-transplant and HIV-associated lymphoproliferative disorders). T-cell lymphoproliferative disorders that have been reported to be EBV associated include a subset of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphoma, extranodal nasal type natural killer/T-cell lymphoma, and other rare histotypes. EBV encodes a series of products interacting with or exhibiting homology to a wide variety of antiapoptotic molecules, cytokines, and signal transducers, hence promoting EBV infection, immortalization, and transformation. However, the exact mechanism by which EBV promotes oncogenesis is an area of active debate. The focus of this review is on the pathology, diagnosis, classification, and pathogenesis of EBV-associated lymphomas. Recent advances in EBV cell–based immunotherapy, which is beginning to show promise in the treatment of EBV-related disorders, are discussed.
Lost in Translation: Integrating Medical Interpreters into the Multidisciplinary Team
Authors: Schapira Lidia , Vargas Erika , Hidalgo Renzo , Brier Marilyn , Sanchez Lourdes , Hobrecker Karin , Lynch Thomas , Chabner Bruce
Published: May 2008

Learning Objectives

After completing this course, the reader will be able to: Carry out three communication tasks that improve the accuracy of interpretation and increase patient understanding.Provide recommendations for working collaboratively with medical interpreters.Overcome common sources of misunderstanding that result from language and cultural barriers.

CME This article is available for continuing medical education credit at CME.TheOncologist.com

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members.

Professional medical interpreters play a crucial role in mediating language-discordant encounters between cancer patients and oncologists. Trained interpreters allow for timely information exchange that is both accurate and culturally sensitive. Rising numbers of immigrants will increase the demand for interpreters. Medical oncologists need to respond by establishing collaborative practices with interpreters or using remote interpretation services. The article provides specific recommendations for working with medical interpreters and reviews common areas of concern for patients and healthcare professionals facing language and cultural barriers.
Editorial: The Long and Winding Road to Better Cancer Cell–Specific Therapies
Authors: Sleijfer Stefan , Wiemer Erik
Published: May 2008

This editorial considers the efforts to devise cancer cell–specific therapies by Ray-Coquard et al. and Tawbi et al. in the previous issue, and applauds the progress being made by such efforts in this area.