bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombophilia States and Markers of Coagulation Activation in the Prediction of Pediatric Venous Thromboembolic Outcomes: A Comparative Analysis with Respect to Adult Evidence
Authors: Goldenberg Neil A. 
Published: December 2008

AbstractVenous thromboembolism (VTE) in children is an important clinical concern for which risk factors include clinical conditions that incite venous stasis, endothelial damage, or thrombophilia (i.e., hypercoagulability) states. Acquired thrombophilia and markers of coagulation activation are common in pediatric VTE, while potent genetic thrombophilia states are less frequently encountered; nevertheless, the latter are more likely to present in the pediatric age than in older adulthood. Sequelae of VTE and its treatment in childhood survivors include bleeding, persistent or progressive thrombosis, recurrent VTE, and (when venous return from a limb is affected) the development of post-thrombotic syndrome (PTS). The focus of the present review is to discuss the role of tests of thrombophilia and coagulation activation as key predictors of outcome in this disease. Based upon this understanding, coupled with existing knowledge of clinical prognostic factors, new risk-stratified approaches of antithrombotic therapy have emerged for clinical investigation in the field of pediatric VTE.
New Issues in Oral Anticoagulants
Authors: Francis Charles W. 
Published: December 2008

Abstract
Polymorphisms in CYP2C9, a critical cytochrome P-450 enzyme in the metabolism of warfarin, alters its clearance and affects dosing. CYP*1 has higher activity than either the *2 or *3 variants, and patients with the *2 or *3 variants require a lower dose. VKORC1 is the enzyme inhibited by warfarin, and its levels are affected by several polymorphisms that can be divided into high or low level haplotypes, and patients with high level haplotypes require higher warfarin doses. The use of algorithms for dosing that incorporate pharmacogenomic information perform better than those using clinical data alone. Considerable effort is ongoing to develop new oral anticoagulants as alternatives to warfarin, and three agents are in advanced development. Dabigatran is an oral direct thrombin inhibitor that has been compared with enoxaparin for prevention of VTE following hip or knee replacement. Based on non-inferiority results in European trials, it has now been approved for marketing in Europe. Phase III trials with a new oral Xa inhibitor, rivaroxaban, have been completed in hip or knee replacement, and rivaroxaban was superior to enoxaparin in prevention of VTE with no increase in bleeding complications. Phase III studies with apixaban, another oral Xa inhibitor, are in progress. These agents are also being evaluated in large studies for prevention of stroke in atrial fibrillation and for VTE treatment.
Novel Therapies and Role of Transplant in the Treatment of Peripheral T-Cell Lymphomas
Authors: Horwitz Steven M. 
Published: December 2008

AbstractPeripheral T-cell lymphomas (PTCL) are an uncommon, heterogeneous group of non-Hodgkin lymphomas that carry a much poorer prognosis than their more common B-cell counterparts. The most commonly used treatment is CHOP or its variations. However, while the results with CHOP are inadequate, there is little compelling data to suggest a preferred alternate strategy. Many of these alternate strategies have been assembled from retrospective data, small case series, subset analyses, phase II studies and individual experience. The greatest experience with alternative treatments has been with the use of high-dose therapy as consolidation. These approaches are promising, but most of the studies are retrospective and include patients with diverse prognoses, making interpretation difficult. Preliminary results of prospective trials in PTCL are only recently being reported. Perhaps more exciting have been the increasing numbers of new therapies being studied for patients with PTCL. The activities of new drugs are being described in studies specifically for PTCL, and attempts at novel combinations are beginning.
Does Helicobacter pylori Eradication Therapy Result in a Platelet Count Improvement in Adults with Immune Thrombocytopenic Purpura Regardless of H pylori Infection?
Authors: Arnold Donald M. , Stasi Roberto 
Published: December 2008

AbstractA 34-year-old male with a long history of immune thrombocytopenic purpura (ITP) presents to your office. His platelet count is 30 × 109/L and he is clinically stable with no bleeding symptoms. He has read that Helicobacter pylori eradication therapy may be effective for ITP and he asks you about this. You do not have access to reliable tests for H pylori infection (e.g., urea breath test), yet you wonder about the benefit of empiric eradication therapy for your patient.
Limited-Stage Disease: Optimal Use of Chemotherapy and Radiation Treatment
Authors: Radford John 
Published: December 2008

AbstractIn the early years of treatment for limited-stage Hodgkin lymphoma there was an understandable focus on disease elimination. This has been replaced by concerns about the amount and balance of different therapies and eventually, as cure rates improve, a desire to individualize management based on risk factors at presentation and response to initial treatment. In limited stage Hodgkin lymphoma, early success was obtained with wide field radiotherapy but later combined modality approaches were employed to overcome the problem of out of field radiotherapy relapses. The acute and delayed toxicity of alkylating agent based therapies led to their replacement with ABVD and concerns about the late toxicity of radiotherapy resulted in smaller field sizes being first assessed in clinical trial and later introduced into clinical practice. The current standard of care of 3 or 4 cycles of ABVD followed by involved-field radiotherapy in clinically staged patients is the culmination of years of work involving many thousands of patients taking part in clinical trials.Our current focus is on the role of PET imaging and whether a response-adapted approach guided by PET can individualize therapy such that radiotherapy and its attendant late toxicity that impacts on future quality of life and survival can be avoided altogether in a subset of patients.
Primary Mediastinal B-Cell Lymphoma
Authors: Johnson Peter W.M. , Davies Andrew J. 
Published: December 2008

Abstract
Primary mediastinal B-cell lymphoma is a discrete clinicopathologic entity. Molecular analysis reveals it to be distinct from other types of large B-cell lymphoma, and retrospective analysis suggests that it may respond better to multi-agent chemotherapy regimens than to the more commonly used CHOP. The addition of rituximab may mitigate such differences, and may also diminish the role of consolidation radiotherapy, which is often used to treat residual mediastinal masses. For the future the role of FDG-PET scanning requires prospective examination, and it is hoped that this may allow the de-escalation of treatment if it can be shown to yield reliable prognostic information. The relative rarity of this type of lymphoma necessitates international collaboration in clinical trials, with a prospective clinicopathologic study, IELSG 26, already underway.
Molecular Determinants of Treatment Response in Acute Lymphoblastic Leukemia
Authors: Campana Dario 
Published: December 2008

AbstractTreatment response in patients with acute lymphoblastic leukemia (ALL) is best assessed using assays for minimal residual disease (MRD). The degree of leukemia cytoreduction and MRD clearance is determined by the collective influence of multiple factors. Some of these variables are features of the leukemic cells, such as expression of genes that regulate their susceptibility to cytotoxic drugs and their propensity to undergo apoptosis. Gene profiles depend, in turn, on the cell of origin for leukemic transformation, the type of underlying genetic abnormalities and/or epigenetic regulatory mechanisms. Another set of variables is related to the host, such as age and polymorphisms in genes that metabolize drugs, which together with pharmacologic variables, such as drug pharmacodynamics and drug interactions, influence treatment response. Finally, the bone marrow microenvironment where leukemic cells reside can participate in the generation of drug resistance. Altogether, these variables determine treatment outcome in each patient. Full knowledge of the molecular features associated with treatment response is required for precise leukemia prognostication and monitoring, and can provide clues to useful targets for novel therapies.
The Treatment of Adults with Acute Lymphoblastic Leukemia
Authors: Fielding Adele 
Published: December 2008

Abstract
Despite the relatively low incidence of acute lymphoblastic leukemia (ALL) in adults, large national and international collaborations have recently improved our understanding of how to treat ALL in adults. This article documents and examines the current evidence base for a “state of the art” therapy in both Philadelphia chromosome–negative and –positive adult ALL. The article comments upon areas of therapeutic debate, such as the role of bone marrow transplantation. In particular, the controversial subject of whether the superior outcome seen in younger patients is predicated on disease biology or therapeutic strategy is examined closely. Promising approaches under development are also discussed.
Milestones and Monitoring in Patients with CML Treated with Imatinib
Authors: Deininger Michael W. 
Published: December 2008

AbstractImatinib is the therapeutic standard for newly diagnosed patients with chronic myeloid leukemia (CML). Recent updates of the IRIS trial, a study of standard-dose imatinib in newly diagnosed chronic-phase patients treated with 400 mg imatinib daily, suggest a stabilization of progression-free survival curves at a high level, implying that the majority of patients will do well on standard therapy. However, some 20% to 30% of patients will fail on imatinib and require alternative therapies. Identification of those patients likely to fail would be desirable to allow for more intensive therapy up front. After a brief overview of the history of CML, this paper will review current recommendations for staging of CML patients at diagnosis. Next, the various tests used to monitor their response to imatinib will be discussed in the context of the currently accepted criteria for imatinib failure and suboptimal response. Last, approaches to identify high-risk patients at diagnosis will be addressed.
The JAK2V617F Mutation in Polycythemia Vera and Other Myeloproliferative Disorders: One Mutation for Three Diseases?
Authors: James Chloé 
Published: December 2008

Abstract
The discovery of the JAK2V617F mutation has made the diagnosis of polycythemia vera (PV) much easier, but the pathogenesis of PV is still incompletely understood. In particular, it is not yet elucidated how a single mutation can be found in multiple myeloproliferative disorders (MPD) and myelodysplastic syndromes with ring sideroblasts and whether the sole JAK2V617F is sufficient to induce a MPD in humans. Several hypotheses are under investigation such as differences in the targeted hematopoietic stem cells (HSC), host modifier polymorphisms, intensity of JAK2V617F signaling, presence of other somatic mutations, or the presence of a pre-JAK2 event that may vary according to the MPD phenotype. Multiple studies have provided some evidence for and against each hypothesis, but it now seems possible to reconcile these hypotheses into a model that will need to be tested using newly developed tools. Recent investigations have also led to new treatment modalities that could benefit patients with PV.
Paroxysmal Nocturnal Hemoglobinuria: An Historical Overview
Authors: Parker Charles J. 
Published: December 2008

AbstractThe clinical hallmark of paroxysmal nocturnal hemoglobinuria (PNH) is episodic hemoglobinuria, and it was this feature that captured the attention of European physicians in the latter half of the 19th century, resulting in careful observational studies that established PNH as an entity distinct from paroxysmal cold hemoglobinuria and march hemoglobinuria. Curiosity about the etiology of the nocturnal aspects of the hemoglobinuria led the German physician Paul Strübing to develop the prescient hypothesis that the erythrocytes of PNH are abnormally sensitive to hemolysis when the plasma is acidified during sleep because of accumulation of carbon dioxide and lactic acid as a result of slowing of the circulation. Investigation of the intricate pathophysiology that underlies the abnormal sensitivity of PNH erythrocytes to hemolysis in acidified serum produced a number of remarkable scientific achievements that involved discovery of the alternative pathway of complement, identification of the membrane proteins that regulate complement, discovery of a novel mechanism for attachment of proteins to the cell surface, and identification of the genetic basis of the disease. These discoveries were made steadily over a period of more than 100 years, and each generation of physicians and scientists made important contributions to the field. The mysteries of PNH have been solved in a particularly satisfying way because the precision and orderliness of the solutions made clearly understandable what had seemed at the times prior to resolution to be problems of nearly insurmountable complexity. The history of PNH is an inspirational reminder of the elegant complexity of nature, the rewards of curiosity and the power and beauty of science.
Hallux valgus and hallux rigidus: a comparison of impact on health‐related quality of life in patients presenting to foot surgeons in Australia
Authors: Gilheany Mark F , Landorf Karl B , Robinson Priscilla 
Published: December 2008

AbstractBackgroundHallux valgus and hallux rigidus are common foot conditions that lead to a deterioration in health status. Patients with significant pain or deformity from these conditions frequently resort to surgery. In this project, the foot health status of patients with hallux valgus and hallux rigidus presenting to foot surgeons in Australia was compared.MethodsFoot health status was measured in 120 participants using the Foot Health Status Questionnaire (FHSQ), a validated 0 – 100 point health status instrument. All participants had presented for surgical advice regarding hallux valgus/rigidus. The mean age of participants was 48.0 years (SD ± 14.3, range 19 – 79).ResultsIn the sample, 68% of participants were diagnosed with hallux valgus and 32% with hallux rigidus. Participants with hallux rigidus had greater levels of pain and functional limitation compared with hallux valgus. The mean difference for pain was 13.8 points (95% CI 4.6 to 22.9) and the mean difference for function was 15.0 points (95% CI 5.3 to 24.7). Both conditions result in similarly negative levels of impact on shoe fit and overall foot health.ConclusionThis study found measurable differences in foot health status between hallux valgus and hallux rigidus in participants presenting for surgical consultation. While both appear to have a negative impact on health status, hallux rigidus has a more significant impact.
COUP-TFII Is Preferentially Expressed in the Caudal Ganglionic Eminence and Is Involved in the Caudal Migratory Stream
Authors: Kanatani Shigeaki , Yozu Masato , Tabata Hidenori , Nakajima Kazunori 
Published: December 2008

While the cortical interneurons derived from the medial ganglionic eminence (MGE) migrate rather diffusely into the cortex, interneurons that migrate out from the caudal ganglionic eminence (CGE) mainly move caudally into the caudal cerebral cortex and the hippocampus in the form of the caudal migratory stream (CMS) (Yozu et al., 2005). Although transplantation experiments at embryonic day 13.5 had revealed that the migrating cells in these two populations are already intrinsically different in regard to their ability to respond to the CGE environment (Yozu et al., 2005), it is not known how the CGE cells are specified and how their migratory behavior is determined.In this study we showed that, although CGE and lateral ganglionic eminence (LGE) express almost the same marker molecules, LGE cells do not migrate caudally when transplanted into the CGE, suggesting that LGE cells are intrinsically different from CGE cells. We therefore compared the transcriptomes of the CGE, MGE, and LGE, and the results showed thatCOUP-TFIIwas expressed preferentially in the CGE as well as in the migrating interneurons in the CMS. Transplantation experiments revealed that COUP-TFII is sufficient to change the direction of MGE cell migration to caudal when transplanted into the CGE environment, and knockdown ofCOUP-TFIIinhibited the caudal migration of the CGE cells. These results suggest that COUP-TFII is both required and sufficient for the CGE-cell-specific migratory behavior in the caudal direction. Thus, a locally expressed transcription factor determines the migratory direction of the cortical interneurons in a region-specific manner.
Personality in patients with pituitary adenomas is characterized by increased anxiety-related traits: comparison of 70 acromegalic patients with patients with non-functioning pituitary adenomas and age- and gender-matched controls
Authors: Sievers C , Ising M , Pfister H , Dimopoulou C , Schneider H J , Roemmler J , Schopohl J , Stalla G K 
Published: December 2008

ObjectiveAlthough neuropsychiatric and morphological brain alterations in acromegalic patients have been described and a distinct disease personality is clinically suspected, this has never been systematically investigated. We examined whether patients with acromegaly showed an altered personality profile compared with patients with non-functioning pituitary adenomas and healthy controls.Design and methodsIn this cross-sectional study, 70 acromegalic patients and 58 patients with non-functioning pituitary adenomas were compared with 140 mentally healthy population controls, matched for age and gender. Personality traits were measured by standardized personality questionnaires (Eysenck personality questionnaire-RK and tridimensional personality questionnaire).ResultsCompared with healthy controls, acromegalic patients described themselves as distinctly more harm avoidant and neurotic and presented themselves with high social conformity. On harm avoidant subscales, they reported more anticipatory worries and pessimism, higher fear of uncertainty, higher fatigability and asthenia. This personality pattern was not specific for acromegaly, but could similarly be observed in patients with non-functioning pituitary adenomas. However, specific for patients with GH-producing adenomas was an even more reduced novelty-seeking behaviour, especially in terms of lower impulsiveness, compared with patients with non-functioning pituitary adenomas.ConclusionPatients with pituitary adenomas show a distinct pattern of increased anxiety-related personality traits compared with the general population, potentially as a result of the pituitary lesion and/or associated hormonal dysregulations and comorbidities. Acromegaly is additionally associated with reduced impulsivity and novelty-seeking behaviour, which might affect patients' management and their quality of life.
THE GALACTOPOIETIC EFFECT OF IODINATED CASEIN: DOSE RESPONSE RELATIONSHIPS DURING PROLONGED TREATMENT
Authors: LEECH F. B. 
Published: December 2008

1. In an experiment involving fifty-nine cows, the relative values were assessed of daily dosages of 15, 20 and 25 g. of iodinated casein incorporated in cattle cubes. Treatment was continued from 3 months after calving for 28 weeks, except on cows which went dry before this time.
2. The expected increase in milk yield lasted for 8 weeks, after which the response to the two lower doses quickly disappeared. The response to 25 g. of iodinated casein was maintained at a reduced level throughout the period of treatment.
3. The yield of butter fat reacted very similarly to milk yield.
4. There was no effect on the proportions of butter fat or of non-fatty solids in the milk.
5. Body weight was reduced by amounts proportional to the doses; this loss in weight gradually disappeared. After 12 weeks of treatment there were no significant differences between the groups.
6. There was no significant effect on the health of the cows or on their reproductive activity.
BLOOD CHANGES DURING THE ADAPTATION SYNDROME IN SHEEP
Authors: WHITE I. G. 
Published: December 2008

1. The effect of twice-daily injections of formalin, as an agent eliciting the adaptation syndrome, has been studied on the blood constituents of sheep.
2. Within 4 days of the start of injections of 5 ml. of 4 % formalin there was a significant hypochloraemia, hypoglycaemia and leucocytosis with a return to normal levels after 10 days. There was also an intermediate compensatory hyperglycaemia. The leucocytosis was due primarily to a neutrophilia, although there was a slight transient increase in both absolute lymphocyte and eosinophil counts.
3. When the dose rate was increased to 10–20 ml. of 10% formalin, the plasma chloride and leucocyte patterns were repeated and there was also an increase in erythrocytes and haemoglobin values. In the later stages of the experiment the absolute lymphocyte and eosinophil counts were depressed, whilst the absolute monocyte count had risen.
4. There were no significant changes in blood acetone or in the basophil count throughout the experiment.
5. It is concluded that, in general, the blood changes elicited by an alarming stimulus in sheep are similar to those described in small laboratory animals. The renewed response to an increased intensity of stimulus observed in this experiment indicates that resistance is quantitatively as well as qualitatively specific.
EFFECTS OF ANDROSTENEDIONE AND PROGESTERONE ON OESTROUS SWELLING OF THE FERRET VULVA
Authors: HAMMOND J. 
Published: December 2008

Quantitative data are given of the anti-oestrogenic action of progesterone on the vulva of the normal oestrous ferret, and the oöphorectomized animal treated with oestrogen implants. Initial experiments that suggested a similar action of androstenedione, such as has been reported on the mouse vagina, were not confirmed.
Amounts of androstenedione at least 80 times as great as those of progesterone that were effective in collapsing the normal oestrous vulva, and at least 10 times as great as those that antagonized the effect of oestrogen on the vulva and vaginal smear of the castrate, produced no effect.
In view of the different method of administration, among other factors, exact equality of relative anti-oestrogenic potency in mouse and ferret was not to be expected; but the observed difference suggests that androstenedione may be metabolized differently in the two species, the metabolites varying in anti-oestrogenic action.
ANTAGONISM OF VAGINAL ACTIONS OF OESTROGEN BY PROGESTERONE AND OTHER STEROIDS
Authors: ROBSON J. M. , SHARAF A. A. 
Published: December 2008

The inhibition of the vaginal action of oestradiol and several synthetic oestrogens by progesterone, methyl testosterone and testosterone propionate have been studied quantitatively.
The action of the natural oestrogen is more easily inhibited than that of the synthetic oestrogens.