bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Regimen Complexity on Patient Satisfaction and Compliance With Warfarin Therapy
Authors: Hixson-Wallace Julie A. , Dotson Jennifer B. , Blakey Sybelle A.
Published: June 2008

This study sought to determine patient satisfaction with anticoagulation care in a pharmacist-managed clinic and assess the effect of warfarin regimen complexity on patient satisfaction, compliance, and international normalized ratios (INRs). Retrospective chart reviews of 476 anticoagulation clinic patients were conducted. Patients were divided into groups by complexity of warfarin regimen (whole tablet, split tablet, alternating dose) for comparisons of compliance and INRS. An oral Likert scate satisfaction survey was administered to a convenience sample of 100 patients. Degree of satisfaction was compared based on warfarin regimen. Compliant patients were more likely to have therapeutic INRs ( p < 0.01) and to be taking whole tablet dosage regimens ( p < 0.01). Patients were generally satisfied with the pharmacist-managed clinic. There was a significantly (p < 0.025) higher score for patients on split tablet regimens, indicating a greater likelihood for agreement that alternating doses made taking their medication more difficult. A relationship exists between patient compliance and prescribed dosage regimen, as well as with therapeutic INR values.
Ecarin Clotting Time is Sensitive to Heparinoids: Comparison of Two Different Techniques
Authors: Demir Muzaffer , Iqbal Omer , Untch Brian , Hoppensteadt Debra A. , Gaikwad Bhavna S. , Fareed Jawed
Published: June 2008

Ecarin clotting time (ECT) is currently developed for the specific monitoring of antithrombin drugs, such as hirudin, argatroban, and hirulog. Aqueous reagent and dry chemistry technology have become available for ECT monitoring of antithrombin agents. Currently, many heparinoids and heparinomimetic drugs are being developed. These agents activate heparin cofactor 11 (HCII) and primarily mediate their effects by inhibiting thrombin. Atthough the test is specific for antithrombin agents, heparin cofactor II-mediated thrombin inhibitors are capable of prolonging the ECT. In order to study the relative effects of some of these agents, ECT was measured in human plasma supplemented with PI-88 (a sutfated pentomanose ; Progen Industries Limited. Sydney, Australia), aprosulate, pentosan polysulfate, dermatan Sulfate, unfractionated heparin (UFH), and recombinant hirudin (r-hirtadin). All agents were supplemented to the citrited-pooled plasma prepared from 10 healthy volunteers at a graded dosage of 0 to 100 These techniques gave comparable results for all of the agents used (PI-88. r2 = 0.99; r-hirudin, r2= 0.98, UFH. r2 =0.98; dermatan sutfate, r2 = 0.95; aprosulate, r2 = 0.95; pentosan polysulfate, r2 = 0.94). The relative anticoagulant effects of various agents used on ECT varied widely, exhibiting their potency in the following order: r-hirudin = pentosan polysulfate > dermatan sulfate > PI-88 > aprosulate > UFH. The sensitivity of ECT was adjusted by varying the concentration of the ecarin reagent. The results suggest that HCIImediated inhibition of thrombin can be detected by using ECT reagents.
Anticoagulant and Antiprotease Effects of a Novel Heparinlike Compound From Shrimp (Penaeus brasiliensis) and Its Neutralization by Heparinase I
Authors: Demir Muzaffer , Iqbal Omer , Dietrich Carl P. , Hoppensteadt Debra A. , Ahmad Sarfraz , Daud Asif N. , Fareed Jawed
Published: June 2008

Heparin is usually obtained from mammalian organs, such as beef lung, beef mucosa, porcine mucosa, and sheep intestinal mucosa. Because of the increased use of heparin in the production of low-molecular-weight heparin (LMWH), there is a growing shortage of the raw material needed to produce LMWHs. A previous report described the structural features of a novel LMWH from the shrimp (Penaeus brasiliensis). In order to compare anticoagulant and antiprotease effects of this heparin, global anticoagulant tests, such as the prothrombin time, activated partial thromboplastin time, thrombin time, and Heptest®, were used. Amidolytic anti-Xa and anti-IIa activities were also measured. The relative susceptibility of this heparin to flavobacterial heparinase was also evaluated. The United States Pharmacopeia (USP) potency of shrimp heparin (SH) was found to be 28 U/mg. SH produced a concentration-dependent prolongation of all of the clotting tests and exhibited marked inhibition of FXa and FIIa. Heparinase treatment resulted in a marked decrease of the anticoagulant effects and neutralized the in vitro anti-IIa actions. However, the anti-Xa activities were only partially neutralized. Protamine sulfate was only partially effective in neutralizing the anticoagulant and antithrombin effects of SH. SH also produced marked prolongation of activated clotting time, which was neutralized by heparinase but not by protamine sulfate. These results suggest that SH is a strong anticoagulant with comparable properties to mammalian heparins and can be used in the development of clinically useful antithrombotic-anticoagulant drugs.
Plasma Tissue Factor Pathway Inhibitor Levels as a Marker for Postoperative Bleeding After Enoxaparin Use in Deep Vein Thrombosis Prophylaxis in Orthopedics and General Surgery
Authors: Hakki Sam I. , Fareed Jawed , Hoppensteadt Debra A. , Abdullah Hani , Camblin John , Nasseri Andrew F. , Hamadeh Ossama , Wright Terry
Published: June 2008

Low-molecular-weight heparins (LMWH) are widely used as antithrombotic prophylactic pharmaceutical agents in orthopedic and general surgery. Their antithrombotic characteristics are expressed by plasma mediators such as anti-Xa, anti-Ila, and increased release of tissue factor pathway inhibitor (TFPI) from vascular endothelium. The purpose of this clinical research is to study the relation between plasma levels of these mediators and postoperative bleeding.

Forty-one consecutive patients undergoing hip or knee arthroplasty (n = 36) and colectomy (n = 5) received the standard enoxaparin (a LMWH) dose preoperatively (general surgery) or immediately postoperatively (orthopedic surgery). Major bleeding was defined as a postoperative drop of ≥ 5 g/dL) of hemoglobin. The authors observed that there was a linear relationship between an increase in free/total TFPI ratio levels and postoperative bleeding. When that ratio increased by >60%, the hemoglobin dropped to >5 g/dL (n = 13).

This relationship between free/total TFPI ratio increase and postoperative bleeding was statistically significant (P < 0.001). Those who did not bleed (hemoglobin drop was less than 5 g/dL) (n = 28) had a ratio increase (if any) of less than 50%. However, the authors did not observe any statistical relationship between anti-Xa, anti-IIa, or prothrombin time and postoperative bleeding in patients receiving LMWH for deep vein thrombosis prophylaxis in orthopedic and general surgery patients. The authors recommend a pre- and postoperative ratio level measurement whenever major bleeding is anticipated, as adjustments of LMWH dose or frequency might be necessary.
New Strategies of Control
Authors: Lewis Magda
Published: June 2008

This article, detailing the implications of “ethics drift” for critical work in the academy, reports on an ethics challenge to a non-research-based scholarly text. It analyzes how General Research Ethics Boards (GREBs) can threaten academic freedom when they lack a clear definition of “human subject” research, fail to distinguish between empirical research using humans and scholarly engagement of important social/political issues within human contexts, and overstep the limits of their jurisdiction when they agree to arbitrate on scholarship that ought to be resolved through open debated rather than administrative mechanisms. The article emphasizes that in public democratic institutions, those who contribute to decisions and policies, whether through formal process or by informal tacit ideology, are acting not as individuals but as functionaries of the institution and must bear public accountability and its attendant critiques. The article ends with a recommendation for arms-length oversight of the workings of GREBs.
an ILL/ELLip(op)tical po—ETIC/EMIC/Lemic/litic post® uv: ed DUCAT ion recherché repres©entation
Authors: Smith Phil
Published: June 2008

An approximately excessive, already-much-too-full, incomprehensibly elliptical poetics of research representation, this post/conceptual writing/writhing about research explores a poetic, poemic, polemic, politic, post discourse, and describes a new grammar and rhetoric for understanding education and social science. It offers an undiscovered set of metaphors to unpack ed DUCAT ion scanty science. It is a spoken/written langue/tongue piece based on an intentionally outlandish and overwhelming form used by (some) conceptual, and POST poets. Avoiding the never-transparent language that inscribes the offalic and violent taxonomy of norm(&)al academic research Repres©entation, this writ(h)ing outlines, through a flagrantly and literally/littorally entirely tiresome, unspeakably visual and aural word conflagration, a po-etic that begins to de-inscribe the nature of metaphoric, medicalized, ventriloquizing, normative discourse of social science/education.
Old World Sexism Transplanted
Authors: Athens Lonnie
Published: June 2008

When Nick visits the café of his brother-in-law, Lombros, they become embroiled in a heated discussion over who is and who is not genuinely Greek. Nick takes the position that to be a true Greek you must not only have been born and raised in Greece but also speak Greek perfectly. On the other hand, Lombros takes the position that being Greek depends only on how much you love Hellenic culture and thereby what is in your heart. The conversation then turns into the real reason for Nick's visit. He wants to arrange a marriage between their sister-in-law, Penelope, and Yiannos, an older Greek man who owns a thriving restaurant. Yiannos's demand for a virgin bride threatens to doom any possibility of his marrying Penelope, until Lombros's cook, Josephine, saves the day with a fool-proof plan for Penelope to pass the “test of the sheet.”
Festum Asinorum
Authors: Frentz Thomas S.
Published: June 2008

In January 2000, I was diagnosed with cancer. This story tells of my relationships with the medical professionals who treated me. Like Arthur Frank, my goal was to receive the treatment I needed without sacrificing the humanity I valued. Being socialized by my father's self-destructive wolfish approach to authority, I struggle to overcome those tendencies with medical practitioners and to replace them with a more benign canine—the humor-laced, rule-violating, coyote/trickster of ancient mythology, a persona that challenges dehumanizing institutional structures but not always the people who uphold them. This then is a tale of my emerging trickster as I negotiate my treatment options as a cancer patient.
The Wanderer, the Chameleon, and the Warrior
Authors: Murakami-Ramalho Elizabeth , Piert Joyce , Militello Matthew
Published: June 2008

In this article, the authors use their personal narratives and collaborative portraits as methods to shed light on the complexities of developing a research identity while journeying through a doctoral program. Using the metaphors of a wanderer, a chameleon, and a warrior, their narratives represent portraits of experiences faced by doctoral students at the peak of their epistemological and ontological growth. Borrowing from Lawrence-Lightfoot and Davis's alternative methodology of portraiture, the authors create portraits through personal narratives, which provide voice, reflexivity, and context to the stories told. Significant factors that fostered the students' research identity were present within the author's lived experiences and continued to evolve throughout the doctoral program. Inhibiting factors included the negotiation of a temporary loss of identity for full-time students, normative and analytical modes required by doctoral programs, and a lack of consideration for issues of diversity within the doctoral program.
Mitogen-Activated Protein Kinase p38 Pathway in Venous Ulcer Fibroblasts
Authors: Raffetto Joseph D. , Gram Christopher H. , Overman Kristen C. , Menzoian James O.
Published: June 2008

Objective: Venous ulcer fibroblasts (w-fb) have attenuated growth compared to normal fibroblasts (n-fb). The MAPKp38 pathway mediates stress-responses in various diseases. We hypothesize that p38 pathway is altered in w-fb. Methods: W-fb were isolated from venous ulcers and n-fb from the ipsilateral thigh. Fibroblasts were analyzed for phosphorylated p38 using immunoblot. The relation between p38 and w-fb proliferation was assessed with SB203580 (p38 inhibitor). Fibroblasts were treated with bFGF, TNF-a, and IL-1 and p38 expression analyzed. Results: Phosphorylated p38 expression was increased in w-fb (AU%=233.5±59.7, P=0.039) compared to n-fb (AU%=99.9±14.6). W-fb treated with SB203580 demonstrated increased growth compared to untreated w-fb. W-fb treated with bFGF demonstrated decreased p38. TNF-α and IL-1β significantly increase p38 expression. Conclusions: MAPK p38 is up-regulated in w-fb. Regulation of w-fb proliferation is influenced by p38. Altering the p38 pathway in vivo with growth factors or cytokine inhibition may improve fibroblast proliferation and venous ulcer healing.
Delayed Treatment of a Traumatic Left Subclavian Artery Pseudoaneurysm
Authors: Franz Randall W.
Published: June 2008

A 22-year-old man sustained 4 gunshot wounds to the upper torso resulting in left pneumothorax, an expanding right neck hematoma, left humerus fracture, a traumatic arteriovenous fistula from the right subclavian artery to the right brachiocephalic vein, and pseudoaneurysm formation from partial transection of the right subclavian artery. The patient underwent emergent repair of the confluence of the right internal jugular, subclavian and brachiocephalic veins, and laparotomy secondary to compartment syndrome. Seven weeks later, with the pseudoaneurysm enlarged to 6 cm, it was repaired with combined access via the right common femoral artery and right brachial artery. The pseudoaneurysm was covered with a 7 mm × 8 cm fluency-covered stent graft and postdilated with a 7 mm × 4 cm balloon. Postoperatively, the patient had palpable pulses, occlusion of the pseudoaneurysm, and excellent blood flow into the arm.
Headteacher Career Paths in UK Independent Secondary Coeducational Schools
Authors: McLay Margaret
Published: June 2008

This article presents evidence of the similarities and differences in the career paths of men and women who have achieved headships in UK independent coeducational schools. The research comprised a pilot study of interviews with nine female headteachers and a questionnaire sent to male and female heads of coeducational secondary schools. It identifies factors which assisted or hindered career progress Respondents also provided information on the effectiveness of any training and preparation they had received, and outlined those factors in their general preparation they felt particularly useful. The findings are compared to other relevant studies in both the independent and maintained sectors in order to support conclusions and make recommendations to those aspiring to headship and those involved in their preparation and training.
Spiritual Intelligence in Leadership Development
Authors: Luckcock Tim
Published: June 2008

This article is written from the perspective of a practising headteacher in the context of the Leadership Programme for Serving Headteachers (LSPH), now renamed Head for the Future, and builds on an earlier treatment of the ideological background of LPSH and its construction of self in relation to approaches to educational leadership through personal growth. It examines the six leadership styles promoted by this programme (Coercive, Authoritative, Affiliative, Democratic, Pacesetting and Coaching) with a view to exploring their scope for spiritual intelligence in leadership development. In order to carry out this analysis the author deploys the theory of leadership archetypes originally devised by Christopher Hodgkinson in order to help gain a critical ethical perspective on the leadership styles and the notions of both emotional and spiritual intelligence.
Towards a Theory of Mutual Dependency between School Administrators and Teachers
Authors: Elstad Eyvind
Published: June 2008

The aim of this article is to contribute to an improved comprehension of the relations between administrators and teachers. The main argument is that mutual dependency is an operational feature of a school organization. I analyse a school case that shows essential features of the interconnections between the parties. An extensive commitment to ICT combined with a commitment to free work forms created a vulnerable situation. The teachers' loss of control influenced the relationship between teachers and the administrators that after a while developed into tug-of-war bargaining. I employ a model of rational interaction in order to enlarge the repertoire of explanation that is an analytical tool that is little used in the literature about educational management. I conclude that the theory can indeed be a tool of analysis for understanding mutual dependencies, but that the rational reconstruction must include the importance that trust can have for management and leadership. Successful exertion of power requires relational trust.
Persuading Teachers to Adopt Academic Theories (Or Deontological Perspectives in Professional Motivation to Translate Academic Theories into Praxis)
Authors: Thody Angela
Published: June 2008

This article is to encourage debate about the challenges for academics wanting to see our theories translated into practice in schools. Conventional academic articles do not provide information ready for immediate download into daily school practice. Should academics therefore publish in alternative formats and styles as exemplified in the `newspeak' first title for this article? Such formats can catch attention but can over-simplify carefully wrought cautious research. Finding a compromise between these two extremes so that theory can indeed be linked to praxis is part of the debate engendered by the post-modernist disaspora in research methodology. Pluralism in research methodologies has become accepted but pluralism in the ways in which research can be reported is much less common. The article discusses, and provides examples of, professional, traditional and alternative formats and the ethical issues that can arise from these.
The duality of health technology in chronic illness: how designers envision our future
Authors: Lehoux Pascale
Published: June 2008

This essay critically explores the role of technological innovation in the constitution of chronic states and illness. Drawing on the co-construction of technology and society perspective, it focuses more specifically on the way in which innovation designers envisage the enhancement of the chronically ill and build certain kinds of socio-technical configuration to deal with chronic illness. Using the case of `intelligent distance patient monitoring' as an illustration, the paper argues that technology creates as much as it solves the problem of chronic illness. Technology is recursively embedded in chronic illness and it generates dual effects: it constrains and sustains users' daily practices. Only by recognizing technology's duality and eventually transcending it will research and policy initiatives be able to deal creatively and responsibly with the design of our future health experiences.
Making connections through online asthma monitoring
Authors: Langstrup Henriette
Published: June 2008

Objectives: This was an observational study of an online asthma monitoring system in Danish primary care practices aimed at exploring the reasons why information and communication technologies (ICTs) intended to connect chronic patients with their care provider fail to become a durable part of treatment practices.

Methods: An ethnographic case study was performed, including semi-structured interviews conducted with eight Danish general practitioners (GPs) and one nurse, and participant observation of the system in use.

Results: The technology never became a durable part of any of the studied practices. Rather, it was used in different ways (as a patient tool, a nurse intervention tool, or a tool associated with doing clinical research), providing different actors with different kinds of agency.

Discussion: Rather than challenging the clinical autonomy of the GPs or granting the patient with autonomy, the technology affords — through these different enactments — various constellations of agency for the GPs and other actors involved in asthma treatment. Problems met in relation to implementation of ICT for chronic disease management are better understood as instances of negotiating which connections are valuable in clinical work. Specific, ethnographic accounts of the local co-construction of agency and technology can provide more relevant insights into the changes entailed by the introduction of ICT for chronic disease management.
Teledermatology for chronic disease management: coherence and normalization
Authors: Finch Tracy
Published: June 2008

Objective: To explore the importance of `coherence' in the normalization of treatment interventions by examining teledermatology for skin disease management from the perspectives of patients and their advocates.

Methods: Twelve teledermatology services were studied using semi-structured interviews. Participants were patients ( n = 20) and health professionals, managers and patient advocates ( n = 68).

Results: Teledermatology lacked coherence for patients and advocates. It was seen to be different from standard dermatology care, but the objectives of it — what it is for — were neither clear nor understandable to participants. Teledermatology `fitting in' with the patient's own lifeworld appeared to be unlikely for patients suffering a range of skin diseases, as features of teledermatology (e.g. absence of talk with consultant, and diagnostic uncertainty) were incongruent with the wide-ranging needs of patients and limited their participation in management.

Discussion: Healthcare technology may facilitate greater self-management of chronic disease. However, successful normalization of technology for this purpose will require greater understanding of what it means to patients in the context of their experiences of disease and the parameters of their lives.
The Osteogenic Potential of Pseudoarthrosis Tissue and Bone from Human Scaphoid Non-Unions
Authors: QU G. , VON SCHROEDER H. P.
Published: June 2008

Scaphoid fractures have the highest prevalence of non-union in the human body, but little is known about the osteogenic potential of cells at the pseudoarthrosis. It was our goal to determine whether cells isolated from non-unions could be stimulated to differentiate into osteoblasts and produce bone in vitro. Fifteen human scaphoid non-unions were excised during surgery and bone from either side of the non-union and the fibrocartilagenous central regions were harvested. Osteoblastic populations were subcultured from these. The number of bone nodules (colonies of osteoblast cells that produced bone) from all three regions was similar to the number of nodules derived from iliac bone cultures from the same patients. Treatment of cells with rhBMP-2 resulted in a 3- to 10-fold increase in bone nodule formation in vitro from cells derived from the non-unions. These data demonstrate that cells at the pseudoarthrosis have osteogenic capability and can be stimulated by rhBMP-2, possibly increasing the ability to heal.
Clinical Consequences of Different Exsanguination Methods in Hand Surgery. A Double-blind Randomised Study
Authors: BLØND L. , JENSEN N. VENDEL , SØE NIELSEN N. H.
Published: June 2008

A randomised trial was performed in 100 patients in order to evaluate the effectiveness of three commonly used methods of exsanguination (simple elevation, squeeze method and Esmarch bandage) in a clinical setting. The quality and quantity of the exsanguination was evaluated every 5 min by the surgeon and the amount of oozing was observed. Although there was no significant difference between squeezing the arm and Esmarch bandaging, both resulted in significantly better exsanguination than simple elevation. In 22 out of the 100 patients, a small amount of ooze was observed. The oozing was observed significantly more frequently in the patients exsanguinated by simple elevation.
Telephone Clinic Follow-Up Following Carpal Tunnel Decompression
Authors: WILLIAMS M. , AMIN A. , GETGOOD A. , HALLAM P. , CHOJNOWSKI A. J. , CHAPMAN P. G.
Published: June 2008

This paper investigates the feasibility of a telephone clinic follow-up service for patients undergoing carpal tunnel decompression. Six hundred and thirty patients were recruited over a 2-year period and we assessed their outcome and satisfaction level in the service, using a pre-determined questionnaire 6 weeks following surgery. The telephone clinic was overseen by a surgical care practitioner. We followed up 598 patients (93%) in total, and found 42 patients to be dissatisfied with the service (7%). These patients were referred for outpatient consultation and investigation. Most patients were satisfied with their surgical outcome and found the telephone clinic service to be convenient and effective. Cost analysis calculations estimated a potential saving of £45,958 over the 2-year period when compared to standard outpatient consultation. This model has been developed in our trust to follow up patients undergoing similar minor hand surgery.
Closed Reduction and Percutaneous K-Wires Versus Open Reduction and Interosseous Loop Wires for Displaced Unstable Transverse Fractures of the Shaft of the Proximal Phalanx of the Fingers in Industrial Workers
Authors: AL-QATTAN M. M.
Published: June 2008

Seventy-eight male industrial workers with displaced unstable transverse fractures of the shaft of the proximal phalanx of the fingers were divided into two groups: Group 1 ( n = 40 men, mean age = 34 years, range = 22–46 years) was treated with closed reduction and percutaneous K-wires, and Group 2 ( n = 38 men, mean age = 33 years, range = 20–48 years) was treated with open reduction and interosseous loop wire fixation. At final follow-up, the total active motion (TAM) score of the injured finger was graded as excellent, good, fair or poor if it was greater than 240°, 220°, 180° or less than 180°, respectively. Group 2 had significantly better overall TAM scores than Group 1 ( P = 0.03). The complication rate was higher in Group 1 than Group 2 (28% versus 11%) but the difference did not reach statistical significance ( P = 0.084). The results were compared with those reported by other authors and other techniques of fixation of these fractures.
Carpal Tunnel Syndrome: A Case–Control Study Evaluating Its Relationship with Body Mass Index and Hand and Wrist Measurements
Authors: FARMER J. E. , DAVIS T. R. C.
Published: June 2008

This case–control study investigated the associations between the body mass index (BMI), hand and wrist measurements and carpal tunnel syndrome (CTS). The hands and wrists of 50 patients with CTS and 50 age- and sex-matched controls were measured. The right and left wrist indices (wrist depth/wrist width) were significantly greater in CTS patients (mean = 0.71. SD = 0.04) than in the controls (mean = 0.69 SD = 0.04). The hand index (hand length/palm width) and BMI were not significantly different in the two groups. The hand, but not the wrist, index was found to correlate with the BMI. These results provide some support for a causative association between wrist morphometry, as measured by the wrist index, and CTS, but this difference is too small to be of diagnostic value in clinical or epidemiological practice. The results could also suggest that the previously reported association between CTS and the hand index may be secondary to differences in the BMI.
K-Wire Fixation for Extraarticular Transverse/Short Oblique Fractures of the Shaft of the Middle Phalanx Associated with Extensor Tendon Injury
Authors: AL-QATTAN M. M.
Published: June 2008

In a prospective study, 22 cases of extraarticular transverse/short oblique fractures of the shaft of the middle phalanx associated with extensor tendon injury had fixation of the fracture as well as immobilisation of the distal interphalangeal joint using a K-wire. Mobilisation of the proximal interphalangeal and metacarpophalangeal joints was started immediately after surgery. The wires were removed after 6 weeks. No post-operative complications were noted. At final follow-up (mean = 15 weeks, range = 12–24 weeks), 18 of 22 patients obtained excellent and good total active motion (TAM) scores. Stiffness was confined to the distal interphalangeal joint, and hence when the results were re-analysed for motion at that joint only, only 11 patients had excellent and good outcomes.
Oncogenic Kit controls neoplastic mast cell growth through a Stat5/PI3-kinase signaling cascade
Authors: Harir Noria , Boudot Cédric , Friedbichler Katrin , Sonneck Karoline , Kondo Rudin , Martin-Lannerée Séverine , Kenner Lukas , Kerenyi Marc , Yahiaoui Saliha , Gouilleux-Gruart Valérie , Gondry Jean , Bénit Laurence , Dusanter-Fourt Isabelle , Lassoued Kaïss , Valent Peter , Moriggl Richard , Gouilleux Fabrice
Published: June 2008

The D816V-mutated variant of Kit triggers multiple signaling pathways and is considered essential for malignant transformation in mast cell (MC) neoplasms. We here describe that constitutive activation of the Stat5-PI3K-Akt-cascade controls neoplastic MC development. Retrovirally transduced active Stat5 (cS5F) was found to trigger PI3K and Akt activation, and to transform murine bone marrow progenitors into tissue-infiltrating MCs. Primary neoplastic Kit D816V+ MCs in patients with mastocytosis also displayed activated Stat5, which was found to localize to the cytoplasm and to form a signaling complex with PI3K, with consecutive Akt activation. Finally, the knock-down of either Stat5 or Akt activity resulted in growth inhibition of neoplastic Kit D816V+ MCs. These data suggest that a downstream Stat5-PI3K-Akt signaling cascade is essential for Kit D816V-mediated growth and survival of neoplastic MCs.
Rac GTPase isoforms Rac1 and Rac2 play a redundant and crucial role in T-cell development
Authors: Guo Fukun , Cancelas Jose A. , Hildeman David , Williams David A. , Zheng Yi
Published: June 2008

Rac GTPases have been implicated in the regulation of diverse functions in various blood cell lineages, but their role in T-cell development is not well understood. We have carried out conditional gene targeting to achieve hematopoietic stem cell (HSC)– or T-cell lineage–specific deletion of Rac1 or Rac1/Rac2 by crossbreeding the Mx-Cre or Lck-Cre transgenic mice with Rac1loxp/loxp or Rac1loxp/loxp;Rac2−/− mice. We found that (1) HSC deletion of both Rac1 and Rac2 inhibited production of common lymphoid progenitors (CLPs) in bone marrow and suppressed T-cell development in thymus and peripheral organs, whereas deletion of Rac1 moderately affected CLP production and T-cell development. (2) T cell–specific deletion of Rac1 did not affect T-cell development, whereas deletion of both Rac1 and Rac2 reduced immature CD4+CD8+ and mature CD4+ populations in thymus as well as CD4+ and CD8+ populations in spleen. (3) The developmental defects of Rac1/Rac2 knockout T cells were associated with proliferation, survival, adhesion, and migration defects. (4) Rac1/Rac2 deletion suppressed T-cell receptor–mediated proliferation, IL-2 production, and Akt activation in thymocytes. Thus, Rac1 and Rac2 have unique roles in CLP production and share a redundant but essential role in later stages of T-cell development by regulating survival and proliferation signals.
Human natural killer cells exposed to IL-2, IL-12, IL-18, or IL-4 differently modulate priming of naive T cells by monocyte-derived dendritic cells
Authors: Agaugué Sophie , Marcenaro Emanuela , Ferranti Bruna , Moretta Lorenzo , Moretta Alessandro
Published: June 2008

Dendritic cells (DCs) play a crucial role in naive T-cell priming. Recent data suggested that natural killer (NK) cells can influence the capability of DCs to promote Th1 polarization. This regulatory function is primarily mediated by cytokines released in the microenvironment during inflammatory responses involving NK cells. In this study, we show that human NK cells exposed for short time to interleukin (IL)–12, IL-2, or IL-18, promote distinct pathways of Th1 priming. IL-12– or IL-2–conditioned NK cells induce maturation of DCs capable of priming IFN-γ–producing Th1 cells. On the other hand, IL-18–conditioned NK cells induce Th1 polarization only when cocultured with both DCs and T cells. In this case, IL-2 released by T cells and IL-12 derived from DCs during the priming process promote interferon (IFN)–γ production. In contrast, when NK cells are exposed to IL-4, nonpolarized T cells releasing only low levels of IL-2 are generated. Thus, the prevalence of IL-12, IL-2, IL-18, or IL-4 at inflammatory sites may differentially modulate the NK-cell interaction with DCs, leading to different outcomes in naive T-cell polarization.
E-selectin receptors on human leukocytes
Authors: Nimrichter Leonardo , Burdick Monica M. , Aoki Kazuhiro , Laroy Wouter , Fierro Mark A. , Hudson Sherry A. , Von Seggern Christopher E. , Cotter Robert J. , Bochner Bruce S. , Tiemeyer Michael , Konstantopoulos Konstantinos , Schnaar Ronald L.
Published: June 2008

Selectins on activated vascular endothelium mediate inflammation by binding to complementary carbohydrates on circulating neutrophils. The human neutrophil receptor for E-selectin has not been established. We report here that sialylated glycosphingolipids with 5 N-acetyllactosamine (LacNAc, Galβ1-4GlcNAcβ1-3) repeats and 2 to 3 fucose residues are major functional E-selectin receptors on human neutrophils. Glycolipids were extracted from 1010 normal peripheral blood human neutrophils. Individual glycolipid species were resolved by chromatography, adsorbed as model membrane monolayers and selectin-mediated cell tethering and rolling under fluid shear was quantified as a function of glycolipid density. E-selectin–expressing cells tethered and rolled on selected glycolipids, whereas P-selectin–expressing cells failed to interact. Quantitatively minor terminally sialylated glycosphingolipids with 5 to 6 LacNAc repeats and 2 to 3 fucose residues were highly potent E-selectin receptors, constituting more than 60% of the E-selectin–binding activity in the extract. These glycolipids are expressed on human blood neutrophils at densities exceeding those required to support E-selectin–mediated tethering and rolling. Blocking glycosphingolipid biosynthesis in cultured human neutrophils diminished E-selectin, but not P-selectin, adhesion. The data support the conclusion that on human neutrophils the glycosphingolipid NeuAcα2-3Galβ1-4GlcNAcβ1-3[Galβ1-4(Fucα1-3)GlcNAcβ1-3]2[Galβ1-4GlcNAcβ1-3]2Galβ1-4GlcβCer (and closely related structures) are functional E-selectin receptors.
Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD
Authors: Mannino D. M. , Thorn D. , Swensen A. , Holguin F.
Published: June 2008

Chronic obstructive pulmonary disease (COPD) is associated with important chronic comorbid diseases, including cardiovascular disease, diabetes and hypertension.

The present study analysed data from 20,296 subjects aged ≥45 yrs at baseline in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS). The sample was stratified based on baseline lung function data, according to modified Global Initiative for Obstructive Lung Disease (GOLD) criteria. Comorbid disease at baseline and death and hospitalisations over a 5-yr follow-up were then searched for.

Lung function impairment was found to be associated with more comorbid disease. In logistic regression models adjusting for age, sex, race, smoking, body mass index and education, subjects with GOLD stage 3 or 4 COPD had a higher prevalence of diabetes (odds ratio (OR) 1.5, 95% confidence interval (CI) 1.1–1.9), hypertension (OR 1.6, 95% CI 1.3–1.9) and cardiovascular disease (OR 2.4, 95% CI 1.9–3.0). Comorbid disease was associated with a higher risk of hospitalisation and mortality that was worse in people with impaired lung function.

Lung function impairment is associated with a higher risk of comorbid disease, which contributes to a higher risk of adverse outcomes of mortality and hospitalisations.
Effect of fudosteine on mucin production
Authors: Rhee C. K. , Kang C. M. , You M. B. , Yoon H. K. , Kim Y. K. , Kim K. H. , Moon H. S. , Park S. H. , Song J. S.
Published: June 2008

Fudosteine is a novel mucoactive agent, although little is known about how fudosteine decreases mucin production. The present study examined the effects of fudosteine on MUC5AC mucin synthesis and cellular signalling.

An animal model of lipopolysaccharide (LPS)-induced inflammation and a bronchial epithelial cell line model of tumour necrosis factor (TNF)-α-induced inflammation were used. Fudosteine was administered before stimulation with LPS or TNF-α. The MUC5AC mucin levels were assayed and the expression of the MUC5AC gene was measured. Western blotting was carried out for the detection of phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and phosphorylated extracellular signal-related kinase (p-ERK).

MUC5AC mucin synthesis and the expression of the MUC5AC gene were increased by LPS in rats or TNF-α in NCI-H292 cells; these effects were inhibited by fudosteine treatment. After stimulation with LPS or TNF-α, the expression of p-EGFR, p-p38 MAPK and p-ERK were detected. Fudosteine treatment reduced the expression levels of p-p38 MAPK and p-ERKin vivoand of p-ERKin vitro.

The present results suggest fudosteine inhibits MUC5AC mucin hypersecretion by reducing MUC5AC gene expression and the effects of fudosteine are associated with the inhibition of extracellular signal-related kinase and p38 mitogen-activated protein kinasein vivoand extracellular signal-related kinasein vitro.
Heritability of upper airway dimensions derived using acoustic pharyngometry
Authors: Patel S. R. , Frame J. M. , Larkin E. K. , Redline S.
Published: June 2008

Acoustic pharyngometry represents a simple, quick noninvasive method of measuring upper airway dimensions, which are predictive of sleep apnoea risk. The aim of the present study was to assess the genetic basis of upper airway size as determined using pharyngometry.

Participants in the Cleveland Family Study aged >14 yrs underwent three acoustic pharyngometric measurements. Variance component models adjusted for age and sex were used to estimate the heritability of pharyngometry-derived airway measures.

A total of 568 out of 655 (87%) subjects provided pharyngometric curves of sufficient quality. Although African-Americans tended to show narrower airways compared with white subjects, heritability patterns were similar in these two groups. The minimum cross-sectional area exhibited a heritability of 0.34 in white subjects and 0.39 in African-Americans, suggesting that 30–40% of the total variance in this measure is explained by shared familial factors. Estimates were unchanged after adjustment for body mass index or neck circumference. In contrast, oropharyngeal length did not show significant heritability in either ethnic group.

The minimum cross-sectional area of the oropharynx is a highly heritable trait, suggesting the presence of an underlying genetic basis. These findings demonstrate the potential utility of acoustic pharyngometry in dissecting the genetic basis of sleep apnoea.
The relation between paracetamol use and asthma: a GA2LEN European case–control study
Authors: Shaheen S. , Potts J. , Gnatiuc L. , Makowska J. , Kowalski M. L. , Joos G. , van Zele T. , van Durme Y. , De Rudder I. , Wöhrl S. , Godnic-Cvar J. , Skadhauge L. , Thomsen G. , Zuberbier T. , Bergmann K. C. , Heinzerling L. , Gjomarkaj M. , Bruno A. , Pace E. , Bonini S. , Fokkens W. , Weersink E. J. M. , Loureiro C. , Todo-Bom A. , Villanueva C. M. , Sanjuas C. , Zock J-P. , Janson C. , Burney P.
Published: June 2008

Studies from the UK and USA suggest that frequent use of paracetamol (acetaminophen) may increase the risk of asthma, but data across Europe are lacking.

As part of a multicentric case–control study organised by the Global Allergy and Asthma European Network (GA2LEN), it was examined whether or not frequent paracetamol use is associated with adult asthma across Europe. The network compared 521 cases with a diagnosis of asthma and reporting of asthma symptoms within the last 12 months with 507 controls with no diagnosis of asthma and no asthmatic symptoms within the last 12 months across 12 European centres. All cases and controls were selected from the same population, defined by age (20–45 yrs) and place of residence.

In a random effects meta-analysis, weekly use of paracetamol, compared with less frequent use, was strongly positively associated with asthma after controlling for confounders. There was no evidence for heterogeneity across centres. No association was seen between use of other analgesics and asthma.

These data add to the increasing and consistent epidemiological evidence implicating frequent paracetamol use in asthma in diverse populations.
Impact of home mechanical ventilation on health-related quality of life
Authors: Windisch W.
Published: June 2008

The present multicentre study was aimed at comparably assessing the benefits and burdens associated with home mechanical ventilation (HMV).

Hospitalisation, side-effects and health-related quality of life (HRQL) were assessed 1 month and 1 yr following HMV establishment using the Medical Outcome Study 36-Item Short-form Health Survey (SF-36; general HRQL) and the Severe Respiratory Insufficiency (SRI) Questionnaire (condition-specific HRQL).

In total, 85 (27 chronic obstructive pulmonary disease, 29 restrictive thoracic, 17 neuromuscular, nine obesity hypoventilation syndrome and three miscellaneous) out of 135 eligible patients completed the study. Mean±sdSRI summary scale (range 0–100) improved significantly and comparatively in all 85 patients from 49±15 at baseline to 61±15 at 1 month and to 61±16 at 1 yr, but improvements of subscale scores differed amongst subgroups. SF-36 scores also improved, but the SRI was superior in detecting HRQL changes. Facial soreness and dry throat were the most commonly reported side-effects. Patients spent a mean±sdof 12±6 days in hospital at baseline and 3±3 days at each follow-up visit. Only four patients required unplanned hospitalisation.

Overall general and condition-specific health-related quality of life aspects improved following home mechanical ventilation establishment independent of the underlying disease, which, however, has an impact on changes within specific health-related quality of life domains. The need for hospitalisation is low once home mechanical ventilation is carefully established.
Role of monocyte chemotactic protein-3 and -4 in children with virus exacerbation of asthma
Authors: Santiago J. , Hernández-Cruz J. L. , Manjarrez-Zavala M. E. , Montes-Vizuet R. , Rosete-Olvera D. P. , Tapia-Díaz A. M. , Zepeda-Peney H. , Terán L. M.
Published: June 2008

Macrophages play a crucial role in respiratory viral infections. However, the mechanisms by which these cells are recruited locally are not fully understood. The current authors studied the role of the chemokines monocyte chemotactic protein (MCP)-1, -2, -3 and -4 on monocyte/macrophage recruitment during respiratory viral infections. Levels of these chemokines were investigated in nasal aspirates from 6–12-yr-old children suffering from respiratory viral infections, caused by rhinoviruses, influenza viruses, parainfluenza viruses, adenoviruses and respiratory syncytial virus.

MCP-3 and -4 were significantly higher in samples derived from virus-infected children compared with samples from the same children when they had been asymptomatic. Concentrations of both chemokines were found to significantly correlate with the number of recruited nasal macrophages. Chemotaxis assays showed that purified MCP-3 and -4 from nasal aspirates showed biological activityin vitro. There were no significant differences in MCP-1 and -2 levels between both groups.

The present data indicates that monocyte chemotactic protein-3 and -4 may have an important role in macrophage recruitment in children with proven upper respiratory viral infections. These chemokines could be potential targets for therapeutic intervention in respiratory viral infections.
An epidemic of silicosis among former denim sandblasters
Authors: Akgun M. , Araz O. , Akkurt I. , Eroglu A. , Alper F. , Saglam L. , Mirici A. , Gorguner M. , Nemery B.
Published: June 2008

Sandblasting denim using silica has emerged as a new cause of silicosis in Turkey. Following the discovery of several cases of silicosis in (young) workers who used this process, the frequency and main occupational risk factors of silicosis among former denim sandblasters in the region of Erzurum (Turkey) were evaluated.

Demographic characteristics and information on working conditions were obtained by questionnaire and interview. In addition, spirometry testing was performed and chest radiographs were evaluated according to International Labour Office (ILO) classification of pneumoconioses in 157 former denim sandblasters.

All subjects were male, with a mean (range) age of 23 (15–44) yrs. They had worked for a mean (range) of 36 (1–120) months, starting employment at a 17 (10–38) yrs of age. Most subjects (83%) had respiratory symptoms, especially dyspnoea (52%) but also chest pain (46%). Radiological evidence of silicosis (ILO score 1/0 or higher) was present in 77 (53%) out of 145 subjects with interpretable chest radiographs. These subjects had lower forced expiratory volume in one second and forced vital capacity. The risk of silicosis correlated with seniority (i.e.working as a foreman), exposure duration and number of places of work.

Considering the high prevalence rate of silicosis in such workplaces, further problems are inevitable in the future unless effective measures are taken.
Clinical and polygraphic evolution of sleep-related breathing disorders in adolescents
Authors: Sánchez-Armengol A. , Ruiz-García A. , Carmona-Bernal C. , Botebol-Benhamou G. , García-Díaz E. , Polo-Padillo J. , López-Campos J. L. , Capote F.
Published: June 2008

It has been suggested that sleep-related breathing disorders (SRBD) involve a continuum that develops over the course of life. If modifiable factors could be identified, the progression of SRBD could perhaps be addressed early in life. Although some studies have looked at the evolution of SRBD in pre-pubertal children, very few studies obtained data in adolescents.

Anthropometric, clinical and polygraphic variables were collected during a 4-yr follow-up study among 148 normal adolescents after initial cross-sectional analysis.

From a total of 267 adolescents studied at baseline (mean±sdage 14.3±2.1 yrs), 148 (55.4%) were followed up for 4 yrs. During follow-up, there were no significant changes in snoring and polygraphic parameters. However, a tendency toward weight gain with centrally distributed fat was observed. Habitual snorers had a significantly higher body mass index and more centrally distributed fat than nonsnorers. Males had a higher snoring prevalence and a higher number of respiratory events than females. Snoring at baseline, male sex and poor academic performance were significant predictors of snoring at follow-up.

Snoring tends to persist during adolescence and male sex acts as a risk factor. A relationship between snoring and academic performance was observed. These findings may have implications for long-term management of sleep-related breathing disorders.