bluuebunny/crossref_metadata_2025 huggingface dataset:
General Mental Health, Quality of Life and Suicide-Related Attitudes Among Kurdish People in Iran
Authors: Mofidi N. , Ghazinour M. , Araste M. , Jacobsson L. , Richter J.
Published: August 2008

Aim: To investigate (1) general mental health, (2) quality of life and (3) suicide-related attitudes in Kurds living in Iranian Kurdistan.

Methods: Cross-sectional investigation; cluster random sampling procedure; 1,000 Kurds were randomly selected from 1,000 of 68,000 households in Sannandaj City, Iran; General Health Questionnaire (GHQ-12); Questionnaire on Attitudes Towards Suicide (ATTS).

Results: About 27% of the subjects had to be regarded as probably suffering from a psychological disturbance. There was no gender difference regarding the number of `cases'. These possible `cases' were younger than `non-cases'. The most `cases' occurred among the unemployed. An increasing number of experiences related to suicide and the increasing emotional closeness of those experiences was found to be related to an increased probability that the individual would be classified as a `case' according to the GHQ-12 total score. Unmarried individuals more often evaluated their overall quality of life as `moderate' or `bad' compared to married individuals. Unemployed people, self-employed people and housewives formed the groups who most often reported a `very bad' or `bad' quality of life.

Conclusions: Kurdish people in Iran are in need of facilities and interventional programmes aiming to improve general mental health.
Family Structure and Mediators of Adolescent Drug Use
Authors: Broman Clifford L. , Xin Li  , Reckase Mark
Published: August 2008

This study investigates how family structure is associated with adolescent drug use and how parenting, peer use, religiosity, and neighborhood problems may mediate the relationship. The authors use structural equation modeling to examine the relationship between family structure and drug use across race, and examine potential mediators. Using data from a nationally representative sample of adolescents, the authors find that family structure has little impact on adolescent drug use once potential mediators are accounted for. Though there is minimal direct effect of family structure on adolescent drug use, family structure is significantly correlated with the four mediators. Although there is some variation in the impact of these mediators on adolescent drug use across race/ethnicity, comparison of structural models suggests these variations are not statistically significant. Possible limitations of the findings are discussed.
The term return in the Palestinian discourse on the Right of Return
Authors: Kuzar Ron
Published: August 2008

The term return is used in the English texts of contemporary Palestinian political authors writing on the Right of Return of Palestinians to their homes and homeland. The first part of this article is dedicated to a semantic analysis of return as a radial category with a core meaning and extensions. The meanings of return in these texts as used in the discourse of Palestinian maximalists versus pragmatists are then discussed. It is shown that: (1) different meanings of return are selected according to whether the writer is a maximalist or a pragmatist, and (2) a reality that harmonizes with these meanings is narratively constructed.
Interruptions, status and gender in medical interviews: the harder you brake, the longer it takes
Authors: Menz Florian , Al-Roubaie Ali
Published: August 2008

Discourse research has repeatedly dealt with interruptions as indicators of power and dominance, especially in the context of gender and status. But little research has used doctor—patient communication as a database. From a total of 576 medical interviews, 48 were selected for a qualitative context-bound in-depth analysis of interruptions and were evaluated statistically. Our findings support a differentiated interpretation: regardless of gender, physicians use more non-supportive interruptions than patients ( p = 0.000); patients failed to interrupt physicians more frequently than vice versa ( p = 0.034), even more so with senior physicians than with doctors-in-training ( p = 0.003). Here, status seems to be the decisive variable. However, both female patients and female doctors produced more supportive interruptions than males ( p = 0.013). Furthermore, contrary to intuition, we were able to show that interviews take longer the more physicians interrupt. The article closes with a critical discussion concerning the conjunction of qualitative and quantifying methods within discourse analysis.
TP508 (Chrysalin®) Reverses Endothelial Dysfunction and Increases Perfusion and Myocardial Function in Hearts With Chronic Ischemia
Authors: Fossum Theresa W. , Olszewska-Pazdrak Barbara , Mertens Michelle M. , Makarski Lori A. , Miller Matthew W. , Hein Travis W. , Kuo Lih , Clubb Fred , Fuller Gerald M. , Carney Darrell H.
Published: August 2008

Endothelial dysfunction (ED) is characterized by impaired nitric oxide (NO) signaling, decreased NO-dependent vasodilatation, increased vascular inflammation, and diminished response to angiogenic factors. TP508 (Chrysalin®), an angiogenic tissue repair peptide, was tested for potential effects on myocardial revascularization and ED using a porcine model of chronic myocardial ischemia. TP508 increased perfusion in ischemic regions up to16-fold ( P < .02) and doubled myocardial wall thickening ( P < .02) relative to placebo controls. Ischemic arterioles exhibited impaired NO-mediated vasodilation and diminished NO production. TP508 reversed ischemic effects, increasing NO-mediated vasodilation ( P < .05), endothelial nitric oxide synthase (eNOS) expression, and NO production. In human endothelial cells, TP508 stimulated eNOS activation (1.84 ± 0.2-fold; P < .02), increased NO production (85 ± 18%; P < .02), and prevented hypoxia-induced eNOS downregulation ( P < .01). Thus, TP508 reverses ED both in porcine ischemic hearts and cultured human endothelial cells. These results suggest potential therapeutic benefit of TP508 in myocardial revascularization and treatment of ED-related diseases.
Risk Factors for Physical Injury Among Help-Seeking Battered Women
Authors: Mechanic Mindy B. , Weaver Terri L. , Resick Patricia A.
Published: August 2008

Physical injuries among battered women represent risks for both acute and long-term physical health functioning. The current study assessed the nature and extent of minor and severe injuries among a help-seeking sample of battered women. Hierarchical regression analyses were conducted to assess the unique roles of physical violence, sexual coercion, psychological abuse, and stalking to the prediction of minor and severe injuries in battered women. Not unexpectedly, length of relationship abuse and severity of physical aggression were the most robust predictors of minor and severe physical injuries. Consistent with other research findings, psychological abuse and stalking, as a block, contributed uniquely to the prediction of severe injuries. Results are discussed in terms of implications for future research and intervention with battered women.
WebQuests
Authors: Maxwell Susan M.
Published: August 2008

The nursing shortage, coupled with growing case loads, limits the available time for nurses in home care to attend continuing professional education programs necessary to keep abreast of the changes in nursing practice and enhance their clinical competency. The purpose of this case study was to evaluate the effectiveness of the WebQuest, a Web-based inquiry-oriented model congruent with the pedagogical approaches and cognitive activities commonly used with nursing education, in providing continuing education content to nurses in a mid-sized home health care agency. A convenience sample of registered nurse case managers completed a researcher-designed WebQuest, modified for independent learning, on diabetes education utilizing their personal computers from home. WebQuests proved to be an innovative and creative approach to provide new information, promote higher level thinking skills, and develop nurses' confidence with computer technology.
Examining Offending Specialization in a Sample of Male Multiple Homicide Offenders
Authors: Wright Kevin A. , Pratt Travis C. , DeLisi Matt
Published: August 2008

The American public's fascination with multiple homicide offenders—individuals who seemingly transcend the heinousness of “regular” homicide offenders because of their multiple victims—has grown during the past few decades. Such growth has not, however, been matched by a proportional increase in serious scholarly attention concerning whether those who kill repeatedly are, or are not, “generally” deviant. As a way of moving beyond this problem, the current analysis builds on recent work concerning multiple homicide offenders to investigate the degree to which such offenders are, in fact, more specialized in their offending careers than are other homicide offenders. The implications for continued theoretical development and empirical research are discussed.
The Impact of Value Congruence on Consumer-Service Brand Relationships
Authors: Jing Zhang  , Bloemer Josée M. M.
Published: August 2008

By integrating results from literature pertaining to social psychology, organizational behavior, and relationship marketing, the authors develop and test a model that explains how value congruence affects the key components of consumer-brand relationship quality and outcomes, including satisfaction, trust, affective commitment, and loyalty. Using structural equation modeling, they test the model with data from a survey of 1,037 consumers of clothing stores and banks in the Netherlands. The results show that value congruence has significant direct, positive effects on satisfaction, trust, affective commitment, and loyalty. Furthermore, value congruence indirectly influences loyalty through satisfaction, trust, and affective commitment. The authors discuss the implications of these findings for marketing theory and practice.
Determinants of sick-leave duration: A tool for managers?
Authors: Flach Peter A. , Krol Boudien , Groothoff Johan W.
Published: August 2008

Aims: To provide managers with tools to manage episodes of sick-leave of their employees, the influence of factors such as age, gender, duration of tenure, working full-time or part-time, cause and history of sick-leave, salary and education on sick-leave duration was studied. Method: In a cross-sectional study, data derived from the 2005 sick-leave files of a Dutch university were examined. Odds ratios of the single risk factors were calculated for short spells (≤7 days), medium spells (8— 42 days), long spells (43—91 days) or extended spells (≥91 days) of sick-leave. Next, these factors were studied in multiple regression models. Results: Age, gender, duration of employment, cause and history of sick-leave, salary and membership of scientific staff, studied as single factors, have a significant influence on sick-leave duration. In multiple models, this influence remains for gender, salary, age, and history and cause of sick-leave. Only in medium or long spells and regarding the risk for a long or an extended spell do the predictive values of models consisting of psychological factors, work-related factors, salary and gender become reasonable. Conclusions: The predictive value of the risk factors used in this study is limited, and varies with the duration of the sick-leave spell. Only the risk for an extended spell of sick-leave as compared to a medium or long spell is reasonably predicted. Factors contributing to this risk may be used as tools in decision-making.
Norhealth: Norwegian Health Information System
Authors: Trewin Cassie , Strand Bjørn Heine , Grøholt Else-Karin
Published: August 2008

Norhealth (www.norgeshelsa.no) is a web-based health information system that monitors health and health related conditions, including risk- and protective factors, over time. Norhealth was developed to create a knowledge base for health promotion and prevention strategies in Norway and is targeted at politicians, decision makers, media, students and health professionals. Norhealth has a Norwegian and English version.

Users of Norhealth can create their own tables, graphs, time series, maps and radar diagrams. Most Norhealth elements can be exported to PDF and tables can also be exported to Excel. Norhealth elements can also be pasted into Word or PowerPoint.

Norhealth has 40 health indicators, but aims to reach 70. The indicator list corresponds roughly to the European Community Health Indicators (ECHI) short list. Data is presented at the national and regional level and by age group and gender. Around 50 fact sheets are written in Norwegian.

Future developments include linking fact sheets to figures in Norhealth, writing annual health reports, translating fact sheets to English, improving user friendliness, adding more health indicators and monitoring social inequalities in health. Conclusions: Norhealth is an interactive web-based health information system that was developed to create a knowledge base for health promotion and prevention strategies in Norway.
Incidence and recurrent work-related violence towards healthcare workers and subsequent health effects. A one-year follow-up study
Authors: Hogh Annie , Sharipova Muborak , Borg Vilhelm
Published: August 2008

Aims: The aim of the present study was to analyse the incidence of violence and threats of violence during the first year at work after graduating as a healthcare worker, the risk of re-exposure and health effects among respondents previously exposed to violence or threats. Methods: We analysed baseline data from 5,696 healthcare students and conducted prospective multinomial regression analyses following 2,847 respondents during their first year of employment. Results: At baseline we found that nearly a third of the respondents had been exposed to violence or threats of violence, 8.7% during trainee periods. At follow-up, we found that 24.6% of the healthcare workers had been exposed to violence and 33.4% to threats during the first year at work after graduation. Exposure to violence or threats during trainee periods was a strong predictor of violence (Odds ratio (OR)=3.3) and threats (OR=4.2) at follow-up. The results showed that violence or threats in previous jobs or at other places had a significant impact on the health of the victims at follow-up independent of gender, age, sense of coherence, self-efficacy and health at baseline. Exposure during trainee periods had a small but not quite significant (p=0.06) impact on the health of the victims at follow-up. Conclusions: The study shows a high risk of violence and threats of violence among healthcare workers during training and the first year at work after graduation, indicating a need for violence prevention planning involving both college and workplaces.
Fluids as oxygen carriers and the potential role in trauma resuscitation
Authors: Shirley Peter J
Published: August 2008

Patients with major trauma present a challenge, often using large quantities of banked blood both at the time of injury and during their hospital stay. Blood transfusion is not without risk and is associated with high costs; it is immunosuppressive, rendering patients more susceptible to infection. In the western world, banked blood is fully screened and relatively safe; the same is not true in parts of the developing world, where high rates of HIV carriage make blood transfusion a risky undertaking. Additionally, blood transfusion as a vector for transmission of illnesses such as prion disease is a distinct possibility, for both the developed and developing world alike. The introduction of artificial blood substitutes would ameliorate some risk and also remove the cost of extensive blood testing. For trauma outside hospital, blood substitutes could compete directly with fluid resuscitation as donated blood is not usually available. Patients with prolonged transport times would appear to be the most obvious beneficiaries and volume expansion, along with improvement in oxygen-carrying capacity would be the ultimate goal. All clinicians confronted with the need for transfusion of homologous blood would welcome the development of a safe and reliable alternative to red blood cells in order to ensure oxygen transport to the tissues. However, even though research on red cell substitutes started more than 100 years ago, even now none of the heavily investigated compounds based on haemoglobin or perfluorocarbons has been released in Europe or the USA for routine clinical use.
Acetabular fractures in the 21st century
Authors: Rickman M. , Bircher MD
Published: August 2008

Acetabular fractures are uncommon other than in the polytrauma setting, and most orthopaedic surgeons will never develop a wide exposure to them. The early management of these injuries can have profound effects on the long term outcomes from what is often a significant injury in a young patient. We present a current review of the anatomy, classification and management guidelines for acetabular fractures, including a comprehensive review of the major decision making processes, as well as describing the most common complications and the expected outcomes.
Injuries to the proximal humerus
Authors: Costan Lucian , Ashwood Neil
Published: August 2008

Five to seven percent of all fractures involve the humerus, with most occurring in ladies over the age of 60 who have osteoporosis. and suffer fractures after a simple fall. In younger individuals such fractures result from high energy injuries (road traffic accidents). Around 75% are non-displaced fractures according to Neer's classification and can be treated non-operatively. The remaining 25% require surgical intervention based on the understanding of the anatomy of the proximal, the mechanism of the injury and the quality of the patient's bone. The displaced fractures may lead to avascular necrosis, osteoarthritis, pseudoarthrosis, and reduced motion and function. Involvement of the specialist is needed at an early stage in order to restore the limb functionality and the quality of life.
Antimitotic Drug Injections and Radiotherapy: A Review of the Effectiveness of Treatment for Hypertrophic Scars and Keloids
Authors: Wang Xi-Qiao , Liu Ying-Kai , Wang Zhi-Yong , Wei Jun  , Jiang Yu-zhi , Qing Chun  , Lu Shu-Liang
Published: August 2008

Scars are a common complication of surgery or burn wound management. Scars occur over the body, affecting people of both sexes and all ages. Scar therapy is a constant clinical challenge; antimitotic drugs and radiotherapy are used with varying degrees of success. This article examines the success of both these types of treatment modalities.
Pathologic Scars: An Overview of Surgical Strategies
Authors: Téot Luc
Published: August 2008

In most cases pathologic scars are managed using surgical procedures. In recent decades a trend towards the generalized use of flaps has been observed. Skin expanders have been applied for a while and are still useful in postburn alopecia. Large surfaces are being treated more and more with skin substitutes. These are mainly dermal substitutes covered with partial thickness skin grafts. These procedures can be combined in order to cover very large skin surfaces. Prefabricated flaps are based on angiogenesis induction via vessel carriers implanted in the depth of the skin structure. The use of skin substitutes limits skin harvesting, which may be a source of scarring.
Intralesional Cryosurgery for the Treatment of Hypertrophic Scars and Keloids Following Aesthetic Surgery: The Results of a Prospective Observational Study
Authors: Har-Shai Yaron , Brown Wifred , Labbé Daniel , Dompmartin Anne , Goldine Irina , Gil Tamir , Mettanes Issa , Pallua Norbert
Published: August 2008

Hypertrophic scars and keloids following aesthetic surgery, which ignite patient dissatisfaction, are difficult to handle. Intralesional cryosurgery for the treatment of such scars has been introduced. This study was designed to evaluate the efficacy of this technology in the treatment of such scars and to assess the reduction of dissatisfaction. Eleven scars (on 11 patients) were treated by intralesional cryosurgery, following breast surgery, otoplasty, face-lifting, and brachioplasty. Each patient scored the concern from the scar and the scar deformity (scale from 1 to 5) prior and following treatment (higher score represents least satisfaction and a severe deformity). The follow-up period was between 3 months and 8 years. The results demonstrated a significant reduction in concern and deformity scores compared with before the cryotreatment ( P = .001). The intralesional cryosurgery technique provides the plastic surgeon with an effective instrument to treat hypertrophic scars and keloids following aesthetic surgery, thus reducing the dissatisfaction of patients.
Avotermin: A Novel Antiscarring Agent
Authors: Durani Piyush , Occleston Nick , O'Kane Sharon , Ferguson Mark W. J.
Published: August 2008

Published literature shows that both physicians and their patients are highly concerned about scarring, even relatively minor scars and those that can be concealed by clothing. Furthermore, both patients and their physicians value any opportunities to improve or minimize scarring. While a range of treatment paradigms have been evaluated, no single therapy has been adopted as a universally accepted standard of care and, currently, there are no marketed pharmaceuticals for the prophylactic reduction of scarring. Many of the available treatments are used empirically and most have not been evaluated in robust prospective, randomized, controlled clinical trials. To address this unmet medical need, translational research into the molecular mechanisms of scarring has led to the discovery and commercial development of a new class of prophylactic medicines that promote the regeneration of normal skin and improve scar appearance. Avotermin, the first agent identified in this class, is the clinical application of human recombinant transforming growth factor β3 (TGFβ3), a key protein involved in scar-free healing observed in embryos. Controlled, double-blind, randomized phase I/II clinical studies have shown that avotermin, administered as an intradermal injection at the time of surgery, leads to both short-term and longer-term (at ≥12 months) improvements in the appearance of scars compared with placebo and standard wound care.
Analysis of Abdominal Wounds Made by Surgical Trocars Using Functional Luminal Imaging Probe (FLIP) Technology
Authors: McMahon Barry P. , O'Donovan Deidre , Donghua Liao  , Jingbo Zhao  , Schiretz Rich , Heninrich Russell , Gregersen Hans
Published: August 2008

The aim was to use a novel functional luminal imaging probe for evaluation of wound defects and tissue damage resulting from the use of trocars. Following general anesthesia of 4 adult pigs, 6 different trocars were randomly inserted at preselected locations in the porcine abdominal wall. The functional luminal imaging probe was used to profile the trocar holes during bag distension from 8 axial cross-sectional area measurements. The cross-sectional areas and pressure in the bag were recorded and exported to Matlab for analysis and data display. Geometric profiles were generated, and the minimum cross-sectional area and hole length (abdominal wall thickness) were used as endpoints. Successful distensions were made in all cases. The slope of the contours increased away from the narrowest point of the hole. The slope increased more rapidly toward the inner abdominal wall than toward the outer wall. The slope of the linear trend lines for the cross-sectional area—pressure relation represents the compliance at the narrowest point in the wall. The hole length (abdominal wall thickness) could be obtained at different cross-sectional area cutoff points. A cutoff point of 300 mm2 gave good results when compared to the length of the hole measured after the tissue was excised. This technique represents a new and straightforward way to evaluate the effects of trocars on the abdominal wall. It may also prove useful in comparing techniques and technology from different manufacturers.
A Dual Benefit of Sacral Neuromodulation
Authors: Indar Adrian , Young-Fadok Tonia , Cornella Jeffrey
Published: August 2008

Sacral neuromodulation is a therapeutic option for women with detrusor overactivity and more recently has been used in patients with fecal incontinence and slow-transit constipation. A 47-year-old woman presented with chronic constipation since childhood. She used multiple laxatives, fiber supplements, and enemas, all without success, and defecated only once per week. Extensive investigations, including barium enema, colonoscopy, defecating proctography, pelvic magnetic resonance imaging, and anorectal manometry all were normal. A transit study showed delayed small-bowel emptying. Colonic transit could not be accurately interpreted because of the marked delayed in proximal transit. An ileostomy was being considered to defunction the colon after the patient become desperate for a better quality of life. She also complained of severe urinary frequency and incomplete emptying. A cystoscopy was normal, and a temporary sacral neuromodulation device was inserted as a staged procedure to improve her urinary symptoms. From the day of device placement and thereafter, the patient defecated without difficulty and has also been free of bladder symptoms. Repeat colonic transit has shown normalization of the stomach, small bowel, and colon.
Endolumenal Fundoplication With EsophyX: The Initial North American Experience
Authors: Bergman Simon , Mikami Dean J. , Hazey Jeffrey W. , Roland Jason C. , Dettorre Rebecca , Melvin W. Scott
Published: August 2008

EsophyX is a novel endolumenal therapeutic option for the treatment of gastroesophageal reflux disease (GERD). The device is passed into the stomach, where it deploys a series of full-thickness fasteners to create a neogastroesophageal valve. The objective of this study was to demonstrate the safety and characterize the effectiveness of this approach in the initial North American experience. This is a retrospective study of consecutive patients with GERD who had undergone endolumenal fundoplication with the EsophyX device. At follow-up, proton pump inhibitor usage was elicited and 2 validated questionnaires were administered measuring GERD health—related quality of life (range 0-50) and symptom severity (range 0-72). In limited preliminary evaluation, the initial North American experience with endolumenal fundoplication using the EsophyX device is that it appears to be safe and provides moderate effectiveness in treating the symptoms of GERD. Further studies comparing this technique with conventional medical and surgical therapies are necessary.
High Definition in Minimally Invasive Surgery: A Review of Methods for Recording, Editing, and Distributing Video
Authors: Kelly Christopher R. , Hogle Nancy J. , Landman Jaime , Fowler Dennis L.
Published: August 2008

The use of high-definition cameras and monitors during minimally invasive procedures can provide the surgeon and operating team with more than twice the resolution of standard definition systems. Although this dramatic improvement in visualization offers numerous advantages, the adoption of high definition cameras in the operating room can be challenging because new recording equipment must be purchased, and several new technologies are required to edit and distribute video. The purpose of this review article is to provide an overview of the popular methods for recording, editing, and distributing high-definition video. This article discusses the essential technical concepts of high-definition video, reviews the different kinds of equipment and methods most often used for recording, and describes several options for video distribution.
Single Port Laparoscopic Cholecystectomy With the TriPort System: A Case Report
Authors: Romanelli John Robert , Mark Lisa , Omotosho Philip A.
Published: August 2008

Single port access surgery may be the next generation of minimally invasive surgery. This study reports a recent experience with the TriPort system (trademark pending, Advanced Surgical Concepts, Wicklow, Ireland) to perform a laparoscopic cholecystectomy via a single peri-umbilical incision. To the authors' knowledge, this is one of the first cases of single port laparoscopic cholecystectomy ever performed with this device in the United States. Randomized studies to compare single port laparoscopic cholecystectomy with traditional laparoscopic cholecystectomy, with specific regard to postoperative pain scores, would be helpful in determining how much additional benefit, if any, there is to the patient.
Biomesh Placement in Laparoscopic Repair of Paraesophageal Hernias
Authors: Diwan T.S. , Ujiki M.B. , Dunst C.M. , Swanström L.L.
Published: August 2008

The placement of mesh in the crural closure of paraesophageal hiatal hernia repairs has been shown to decrease hernia recurrence rates. Typical synthetic mesh are easy to use but have high rate of erosion into the esophagus. Alternatively, biologic mesh decrease the risk of erosion, but are more difficult to manipulate, and there is currently no well-described method for securing them. Current fixation techniques of mesh are difficult, cumbersome, incur extra expense, and are not without complications. A method that requires no additional sutures or staples and achieves excellent contact and reinforcement of the crural closure is presented.
Promoting Nutrition for Men's Health
Authors: Melanson Kathleen J.
Published: August 2008

Morbidity and mortality are significantly higher in men than in women and are particularly related to lifestyle-related chronic diseases. Men tend to consume fewer vegetables and fruits than women and fail to meet recommendations for intakes of fats, fibers, and sodium. Men in some population groups tend to consume diets with lower nutrient density than women. Barriers to healthy eating in men include lack of awareness and personal interest, perceptions that foods and diets are “women's business,” lack of social support, and cynicism regarding nutrition messages by health authorities. In addition, many men perceive health-promoting foods as expensive, bland, nonsatiating, and time-consuming to prepare. Research specifically focused on men's health and nutrition is critically needed. Topics to be addressed include biological, psychological, and social correlates of healthy eating in men and nutritional factors particular to chronic disease risk reduction in men. Social, cultural, religious, economic, educational, and other aspects should be taken into account.
Activating mutations in human acute megakaryoblastic leukemia
Authors: Malinge Sébastien , Ragu Christine , Della-Valle Veronique , Pisani Didier , Constantinescu Stefan N. , Perez Christelle , Villeval Jean-Luc , Reinhardt Dirk , Landman-Parker Judith , Michaux Lucienne , Dastugue Nicole , Baruchel André , Vainchenker William , Bourquin Jean-Pierre , Penard-Lacronique Virginie , Bernard Olivier A.
Published: August 2008

Oncogenic activation of tyrosine kinase signaling pathway is recurrent in human leukemia. To gain insight into the oncogenic process leading to acute megakaryoblastic leukemia (AMKL), we performed sequence analyses of a subset of oncogenes known to be activated in human myeloid and myeloproliferative disorders. In a series of human AMKL samples from both Down syndrome and non–Down syndrome patients, mutations were identified within KIT, FLT3, JAK2, JAK3, and MPL genes, with a higher frequency in DS than in non-DS patients. The novel mutations were analyzed using BaF3 cells, showing that JAK3 mutations were activating mutations. Finally, we report a novel constitutively active MPL mutant, MPLT487A, observed in a non–Down syndrome childhood AMKL that induces a myeloproliferative disease in mouse bone marrow transplantation assay.
The biologic properties of leukemias arising from BCR/ABL-mediated transformation vary as a function of developmental origin and activity of the p19ARF gene
Authors: Wang Pin-Yi , Young Fay , Chen Chun-Yu , Stevens Brett M. , Neering Sarah J. , Rossi Randall M. , Bushnell Timothy , Kuzin Igor , Heinrich David , Bottaro Andrea , Jordan Craig T.
Published: August 2008

Recent reports have shown that upon expression of appropriate oncogenes, both stem cells and more differentiated progenitor populations can serve as leukemia-initiating cells. These studies suggest that oncogenic mutations subvert normal development and induce reacquisition of stem-like features. However, no study has described how specific mutations influence the ability of differentiating cell subsets to serve as leukemia-initiating cells and if varying such cellular origins confers a functional difference. We have examined the role of the tumor suppressor gene p19ARF in a murine model of acute lymphoblastic leukemia and found that loss of p19ARF changes the spectrum of cells capable of tumor initiation. With intact p19ARF, only hematopoietic stem cells (HSCs) can be directly transformed by BCR/ABL expression. In a p19ARF-null genetic background expression of the BCR/ABL fusion protein renders functionally defined HSCs, common lymphoid progenitors (CLP), and precursor B-lymphocytes competent to generate leukemia stem cells. Furthermore, we show that leukemias arising from p19ARF-null HSC versus pro-B cells differ biologically, including relative response to drug insult. Our observations elucidate a unique mechanism by which heterogeneity arises in tumor populations harboring identical genetic lesions and show that activity of p19ARF profoundly influences the nature of tumor-initiating cells during BCR/ABL-mediated leukemogenesis.
Long-term increases in lymphocytes and platelets in human T-lymphotropic virus type II infection
Authors: Bartman Melissa T. , Kaidarova Zhanna , Hirschkorn Dale , Sacher Ronald A. , Fridey Joy , Garratty George , Gibble Joan , Smith James W. , Newman Bruce , Yeo Anthony E. , Murphy Edward L.
Published: August 2008

Human T-lymphotropic viruses types I and II (HTLV-I and HTLV-II) cause chronic infections of T lymphocytes that may lead to leukemia and myelopathy. However, their long-term effects on blood counts and hematopoiesis are poorly understood. We followed 151 HTLV-I–seropositive, 387 HTLV-II–seropositive, and 799 HTLV-seronegative former blood donors from 5 U.S. blood centers for a median of 14.0 years. Complete blood counts were performed every 2 years. Multivariable repeated measures analyses were conducted to evaluate the independent effect of HTLV infection and potential confounders on 9 hematologic measurements. Participants with HTLV-II had significant (P < .05) increases in their adjusted lymphocyte counts (+126 cells/mm3; approximately +7%), hemoglobin (+2 g/L [+0.2 g/dL]) and mean corpuscular volume (MCV; 1.0 fL) compared with seronegative participants. Participants with HTLV-I and HTLV-II had higher adjusted platelet counts (+16 544 and +21 657 cells/mm3; P < .05) than seronegatives. Among all participants, time led to decreases in platelet count and lymphocyte counts, and to increases in MCV and monocytes. Sex, race, smoking, and alcohol consumption all had significant effects on blood counts. The HTLV-II effect on lymphocytes is novel and may be related to viral transactivation or immune response. HTLV-I and HTLV-II associations with higher platelet counts suggest viral effects on hematopoietic growth factors or cytokines.
15-deoxy-Δ12,14-PGJ2 enhances platelet production from megakaryocytes
Authors: O'Brien Jamie J. , Spinelli Sherry L. , Tober Joanna , Blumberg Neil , Francis Charles W. , Taubman Mark B. , Palis James , Seweryniak Kathryn E. , Gertz Jacqueline M. , Phipps Richard P.
Published: August 2008

Thrombocytopenia is a critical problem that occurs in many hematologic diseases, as well as after cancer therapy and radiation exposure. Platelet transfusion is the most commonly used therapy but has limitations of alloimmunization, availability, and expense. Thus, the development of safe, small, molecules to enhance platelet production would be advantageous for the treatment of thrombocytopenia. Herein, we report that an important lipid mediator and a peroxisome proliferator–activated receptor gamma (PPARγ) ligand called 15-deoxy-Δ12,14 prostaglandin J2 (15d-PGJ2), increases Meg-01 maturation and platelet production. 15d-PGJ2 also promotes platelet formation from culture-derived mouse and human megakaryocytes and accelerates platelet recovery after in vivo radiation-induced bone marrow injury. Interestingly, the platelet-enhancing effects of 15d-PGJ2 in Meg-01 cells are independent of PPARγ, but dependent on reactive oxygen species (ROS) accumulation; treatment with antioxidants such as glutathione ethyl ester (GSH-EE); or N-acetylcysteine (NAC) attenuate 15d-PGJ2–induced platelet production. Collectively, these data support the concept that megakaryocyte redox status plays an important role in platelet generation and that small electrophilic molecules may have clinical efficacy for improving platelet numbers in thrombocytopenic patients.
Percutaneous sclerotherapy of a giant mediastinal lymphangioma
Authors: Desir A. , Ghaye B. , Duysinx B. , Dondelinger R. F.
Published: August 2008

The present study reports a case of percutaneous sclerotherapy of a giant mediastinal cystic lymphangioma using Ethibloc® (Ethicon, Norderstedt, Germany) and absolute ethanol in a 59-yr-old female.

The tumour, situated predominantly in a retrocardiac location, caused dyspnoea and dysphagia by compression and was considered unresectable. Follow-up computed tomography 3 yrs after treatment showed a 90% volume reduction of the tumour. The patient is currently asymptomatic.

To the best of the present authors’ knowledge, percutaneous transthoracic sclerotherapy of a mediastinal lymphangioma has not previously been reported in the literature available in English.
Neuroendocrine cells of nasal mucosa are a cellular source of brain-derived neurotrophic factor
Authors: Jornot L. , Lacroix J. S. , Rochat T.
Published: August 2008

There is growing evidence for extensive interaction between sensory neurons, immune and mucosal epithelial cells during airway inflammation and hyperreactivity. This neuro-immune cross-talk (neurogenic inflammation) involves different groups of mediators, which include the neurotrophin family (nerve growth factor, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 and -4). Neurotrophins modulate airway inflammation by enhancing sensory nerve excitability and production of neuropeptides, and by interaction with different immune cell types.

In the present study, it was questioned whether airway epithelial cells express BDNF, and if proinflammatory cytokines (tumour necrosis factor-a, interleukin-1β and interferon-?) and a glucocorticoid (budesonide) affect this expression. Primary cultures of nasal epithelial cells were used.

It was found that BDNF was stored in chromogranin A-containing secretory granules of specialised epithelial cells,
i.e.
neuroendocrine cells, and was secreted in a polarised manner. Apical secretion appears to be constitutive, whereas basolateral secretion is markedly enhanced upon stimulation with cytokines. This enhanced basolateral secretion was not due to enhanced synthesis and was not affected by inhibitors of the processing enzymes, such as furin and the metalloproteinases involved in the maturation of BDNF, but was considerably diminished by budesonide.

Therefore, airway mucosa might contribute to neurogenic inflammation through increased secretion of brain-derived neurotrophic factor by neuroendocrine cells under inflammatory conditions.
Sub-acute occupational hypersensitivity pneumonitis due to low-level exposure to diisocyanates in a secretary
Authors: Schreiber J. , Knolle J. , Sennekamp J. , Schulz K. T. , Hahn J. U. , Hering K. G. , Raulf-Heimsoth M. , Merget R.
Published: August 2008

There is virtually no information in the literature about the exposure levels needed to induce hypersensitivity pneumonitis (HP) by diisocyanates. The present study reports a case of occupational HP due to diisocyanates after low-level exposure.

A 53-yr-old female never-smoker developed progressive shortness of breath on exertion, cough, fatigue and flu-like symptoms shortly after she began work as a secretary of a car body repair shop. A diagnosis of HP was made 2 yrs later, based on a restrictive ventilatory defect, a reticulonodular and discrete ground-glass pattern on high-resolution computed tomography, lymphocytosis in bronchoalveolar lavage and specific immunoglobulin G antibodies to diisocyanate human serum albumin conjugates in the patient’s serum.

The diagnosis was confirmed by recovery after exposure cessation and deterioration after re-exposure. Ambient monitoring revealed air concentrations of different diisocyanate monomers below the detection limit in both the patient’s work station and in front of the paint spray booths, with the exception of one measurement that showed 4,4-methylenediphenyl diisocyanate concentrations of 3 µg·m−3in front of one booth (corresponding to a total reactive isocyanate group concentration of 1 µg·m−3).

The present authors conclude that concentrations of diisocyanates far below current exposure limits may induce hypersensitivity pneumonitis in susceptible subjects.
A new perspective on concepts of asthma severity and control
Authors: Taylor D. R. , Bateman E. D. , Boulet L-P. , Boushey H. A. , Busse W. W. , Casale T. B. , Chanez P. , Enright P. L. , Gibson P. G. , de Jongste J. C. , Kerstjens H. A. M. , Lazarus S. C. , Levy M. L. , O'Byrne P. M. , Partridge M. R. , Pavord I. D. , Sears M. R. , Sterk P. J. , Stoloff S. W. , Szefler S. J. , Sullivan S. D. , Thomas M. D. , Wenzel S. E. , Reddel H. K.
Published: August 2008

Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society Task Force, identifies the need for separate concepts of control and severity, describes their evolution in asthma guidelines and provides a framework for understanding the relationship between current concepts of asthma phenotype, severity and control.

“Asthma control” refers to the extent to which the manifestations of asthma have been reduced or removed by treatment. Its assessment should incorporate the dual components of current clinical control (e.g.symptoms, reliever use and lung function) and future risk (e.g.exacerbations and lung function decline).

The most clinically useful concept of asthma severity is based on the intensity of treatment required to achieve good asthma control,i.e.severity is assessed during treatment. Severe asthma is defined as the requirement for (not necessarily just prescription or use of) high-intensity treatment. Asthma severity may be influenced by the underlying disease activity and by the patient's phenotype, both of which may be further described using pathological and physiological markers. These markers can also act as surrogate measures for future risk.
Comparison of techniques for obtaining lower airway epithelial cells from children
Authors: McNamara P. S. , Kicic A. , Sutanto E. N. , Stevens P. T. , Stick S. M.
Published: August 2008

Airway epithelial cells (AECs) are important in asthma as they are the first cells to encounter pathogens/allergens. In children, AECs can be obtained using a “blind” nonbronchoscopic technique through an endotracheal tube. However, due to the increasing use of laryngeal masks the number of children in whom this technique is applicable has become limited. Recently, the present authors began to use a portable “bronchoscope-directed” technique to sample AECs. The current study compares both techniques in both asthmatic and nonasthmatic children.

A total of 81 children undergoing elective surgery, were grouped according to atopic status and respiratory symptoms. Cellular yield of blind and bronchoscope-directed brushings were compared and immunocytochemistry performed. AECs were cultured and cytokine analysis of culture supernatant undertaken.

Both techniques were equally well-tolerated, with the only adverse effect being a cough in 10% of the subjects. The mean±sdcell yield was higher in bronchoscope-directed than blind brushings (5.1±2.4versus3.1±1.4x106 cells). Immunocytochemistry confirmed an epithelial cell lineage. Culture supernatant cytokine concentrations were similar regardless of sampling technique with patterns preserved between asthmatic and healthy nonatopic phenotypes.

Compared with blind brushing portable bronchoscope-directed brushing is well-tolerated, yields significantly more cells and is a potentially quick and useful technique for obtaining airway epithelial cells for research into childhood respiratory disease, specifically asthma.
Haplotype block partitioning as a tool for dimensionality reduction in SNP association studies
Authors: Pattaro Cristian , Ruczinski Ingo , Fallin Danièle M , Parmigiani Giovanni
Published: August 2008

Background

Identification of disease-related genes in association studies is challenged by the large number of SNPs typed. To address the dilution of power caused by high dimensionality, and to generate results that are biologically interpretable, it is critical to take into consideration spatial correlation of SNPs along the genome. With the goal of identifying true genetic associations, partitioning the genome according to spatial correlation can be a powerful and meaningful way to address this dimensionality problem.

Results

We developed and validated an MCMC Algorithm To Identify blocks of Linkage DisEquilibrium (MATILDE) for clustering contiguous SNPs, and a statistical testing framework to detect association using partitions as units of analysis. We compared its ability to detect true SNP associations to that of the most commonly used algorithm for block partitioning, as implemented in the Haploview and HapBlock software. Simulations were based on artificially assigning phenotypes to individuals with SNPs corresponding to region 14q11 of the HapMap database. When block partitioning is performed using MATILDE, the ability to correctly identify a disease SNP is higher, especially for small effects, than it is with the alternatives considered.

Advantages can be both in terms of true positive findings and limiting the number of false discoveries. Finer partitions provided by LD-based methods or by marker-by-marker analysis are efficient only for detecting big effects, or in presence of large sample sizes. The probabilistic approach we propose offers several additional advantages, including: a) adapting the estimation of blocks to the population, technology, and sample size of the study; b) probabilistic assessment of uncertainty about block boundaries and about whether any two SNPs are in the same block; c) user selection of the probability threshold for assigning SNPs to the same block.

Conclusion

We demonstrate that, in realistic scenarios, our adaptive, study-specific block partitioning approach is as or more efficient than currently available LD-based approaches in guiding the search for disease loci.