bluuebunny/crossref_metadata_2025 huggingface dataset:
Antipsychotic drug-induced acute laryngeal dystonia: two case reports and a mini review
Authors: Christodoulou Christos , Kalaitzi Chryssanthi
Published: May 2005

Antipsychotic-induced laryngeal dystonia is a life-threatening side-effect of both high- and low-potency classical antipsychotics, and its diagnosis often remains elusive. We review all cases of acute laryngeal dystonia due to antipsychotics available in the literature, including controversial ones, and add two new cases. There are no reports of acute laryngeal dystonia due to atypical antipsychotics. Antipsychotic-induced laryngeal dystonia has been reported predominantly in young males, but does not correlate to the dosage or the category of the drug. There have been reports of acute laryngeal dystonia due to metoclopramide. Differential diagnosis includes other extrapyramidal side-effects and allergic reactions. Treatment consists of the administration of anticholinergic agents.
Economic Justice
Authors: Hahnel Robin
Published: May 2005

This article argues against contribution-based conceptions of economic justice and in favor of distribution according to effort or sacrifice. It responds to important objections implicit in the work of Robert Nozick and John Rawls, and argues that market socialist economies cannot avoid being inequitable.
Profitability Trends and Cycles: Structural Change in the Mexican Economy
Authors: Etelberto Ortiz C.
Published: May 2005

The article presents a heterodox analysis of the rate of profit. The method is especially useful in situations when there is no reliable information on capital stocks. The article assesses two methods in the Mexican economy: a standard Marxian approach and the author's proposed alternative, labeled profitability trends. The new method can also be used to determine sectoral estimates of profitability.
Refeeding Syndrome and Hypophosphatemia
Authors: Marinella Mark A.
Published: May 2005

Hypophosphatemia is a potentially life-threatening complication of reinstating nutrition in a malnourished patient. Refeeding syndrome is a term that refers to various metabolic abnormalities that may complicate carbohydrate administration in subnourished patient populations. Hypophosphatemia is the most well-known, and perhaps most significant, element of the refeeding syndrome and may result in sudden death, rhabdomyolysis, red cell dysfunction, and respiratory insufficiency. This review briefly examines refeeding-induced hypophosphatemia in the hospitalized patient in hopes of making clinicians more aware of this common, but often overlooked, potentially dangerous problem.
Management of Delirium Tremens
Authors: DeBellis Ronald , Smith Brian S. , Choi Susan , Malloy Michael
Published: May 2005

Delirium tremens is recognized as a potentially fatal and debilitating complication of ethanol withdrawal. Research thus far has primarily focused on the prevention of delirium tremens.
Acute Dystonic Reaction and the Neuroleptic Malignant Syndrome
Authors: White Suzanne R.
Published: May 2005

Up to 90% of patients on chronic antipsychotic therapy will experience adverse neurologic side effects, with many of these effects attributable to the dopamine-blocking properties of these drugs. Even the newer, “atypical” antipsychotics are increasingly associated with neurologic complications. In the acute care setting, these medications have broad application beyond the management of psychiatric illness. Given the extent of their use, clinicians should be familiar with the spectrum of neurological syndromes that can develop. Some are common, such as akathisia, acute dystonic reaction, tardive dyskinesia, and drug-induced parkinsonism. Others, such as the life-threatening neuroleptic malignant syndrome, are rare yet must be recognized early to affect survival and improve outcome. This discussion highlights 2 idiosyncratic syndromes, acute dystonic reaction and neuroleptic malignant syndrome. The differential diagnosis for both syndromes and their management is discussed.
Digoxin: The Monarch of Cardiac Toxicities
Authors: Litonjua M. Regina , Penton Stephanie , Robinson Craig , Daubert G. Patrick
Published: May 2005

The cardiac steroids (or glycosides) are a heterogeneous group of compounds that have been well recognized for both their clinical benefit and inherent toxicity. This review will primarily focus on digoxin because of its widespread clinical use, although the other cardiac steroids will be discussed in less detail. The cardiac steroids have a narrow therapeutic index and remain a significant source of toxicity, with nearly 5000 human exposures reported to the American Association of Poison Control Centers in 2002. Digoxin reversibly binds to the α subunit of the Na+ -K+ ATPase pump and completely inhibits its enzymatic and transport functions. The cumulative effect on cardiac tissue is dependent on the number of Na+ -K+ ATPase pump sites that are occupied by cardiac steroid molecules. It is important to recall the pharmacokinetics of digoxin in that serum digoxin levels drawn prior to tissue distribution (<6 hours) do not accurately reflect acute toxicity. Signs and symptoms of toxicity vary between acute and chronic intoxications. A systematic approach guided by clinical symptoms with early administration of immunotherapy can lead to a significant reduction of morbidity and mortality in digoxin-poisoned patients.
Toxicity of Oral Agents Used to Treat Diabetes
Authors: Lada Pamela , Idrees Umbreen
Published: May 2005

Oral agents used for the management of type 2 diabetes mellitus include sulfonylureas, biguanides, thiazolidinediones, metglitinides, and/or α -glucosidase inhibitors. These medication classes can be further classified as hypoglycemic and antihyperglycemic agents. Hypoglycemia is a major symptom of toxicity of these agents, particularly with the sulfonylureas, including combination medications that include sulfonylureas. In overdose situations, metformin, a biguanide, can lead to considerable gastrointestinal adverse effects and potentially lactic acidosis in severe cases. Data on the management of toxicities of the other classes are limited. This article will review the treatment modalities that have been used for treating symptomatic hypoglycemia and metformin-induced lactic acidosis.
A symbolic defence of animal magnetism: a copperplate engraving by Ludwig Richter as the frontispiece of the account of the somnambulist Auguste K. (1843)
Authors: Montiel Luis
Published: May 2005

The year 1843 saw the publication in Dresden of a comprehensive account of the magnetic treatment of a somnambulist. This date came relatively late in the history of animal magnetism in Germany, and coincided with the decline of the theory in medical circles. Perhaps it was for this reason that the authors commissioned Ludwig Richter, one of the most accomplished engravers of the day, to produce a plate of illustrations which were intended to act as a symbolic defence of the theory. They are examined in this article.
William Menninger and American psychoanalysis, 1946–48
Authors: Plant Rebecca Jo
Published: May 2005

In the aftermath of World War II, a struggle ensued over the direction of American psychoanalysis. Led by William Menninger, who reluctantly assumed the presidency of the American Psychoanalytic Association in 1946, a cohort of American-born psychoanalysts sought to make their profession more responsive to other medical practitioners and the general public. Insisting that divisive theoretical debates should be relegated to the past, these psychoanalysts promoted a medicalized, Americanized and popularized version of psychoanalysis that deliberately blurred the distinction between psychiatry and psychoanalysis. They were opposed by a group of more orthodox psychoanalysts, including many émigrés, who viewed their efforts as undermining psychoanalysis from within.
The 1942 ‘euthanasia’ debate in the American Journal of Psychiatry
Authors: Joseph Jay
Published: May 2005

This paper discusses and analyses three articles appearing in a 1942 issue of the American Journal of Psychiatry. In the first, neurologist Foster Kennedy argued that ‘feebleminded’ people should be killed (an act which he referred to as ‘euthanasia’). The rebuttal was written by psychiatrist Leo Kanner, who argued against ‘euthanasia’. An unsigned editorial discussing these positions clearly sided with Kennedy: that ‘euthanasia’ would be appropriate in some cases, and that parents’ opposition to this procedure should be the subject of psychiatric concern. The arguments are analysed and discussed within the context of eugenics and the murder of mental patients in Germany. Finally, the author points out that currently ascendant genetic theories in psychiatry could be a precursor for future proposals similar to Kennedy’s.
Some origins of cross-cultural psychiatry
Authors: Raimundo Oda Ana Maria G. , Banzato Claudio Eduardo M. , Dalgalarrondo Paulo
Published: May 2005

The interface between insanity, race and culture was a challenging subject for some of the most influential nineteenth-century alienists. Our paper reviews some of the theoretical and clinical investigations of comparative psychiatry of this period. The idea that insanity was supposedly rare among ‘primitive’ people, e.g., Africans, American Natives and some Eastern populations, was repeatedly defended by prominent alienists. Associated with this notion, many authors believed that insanity tends to become more prevalent as civilization evolves. According to them, civilization had an unfavourable effect on insanity rates because it demanded a much higher degree of organization and mental production. Moreover, a greater degree of mental excitation would explain why insanity occurs more frequently in Europe than in the East, Africa or South America. Eventually, at the end of the nineteenth century, the coalition of cross-cultural and neuropsychiatry produced a notion that the brain of the ‘native’ is more simple and crude than that of the civilized, and more vulnerable to the evil effects of civilized life. In conclusion, some ethnocentric bias and racial stereotypes still pervasive in contemporary psychiatry are identified and traced back to their historical origins.
Vladimir Bekhterev: his life, his work and the mystery of his death
Authors: Lerner Vladimir , Margolin Jacob , Witztum Eliezer
Published: May 2005

Bekhterev was one of the prominent scientists of his era. He played a crucial role in the study of the development of the brain’s organization, neurophysiology and neuropathology and in the objective study of psychological phenomena. Due to a trick of fate, Bekhterev’s name and scientific contributions were neglected and consigned to oblivion. In this article we would like to restore the historical injustice done to Bekhterev. Based on newly discovered documents and testimonies, we present little known details about his life history, his clinical work and the tragic circumstances of his death.
Talking Minds: The Scholastic Construction of Incorporeal Discourse
Authors: Carozzi María Julia
Published: May 2005

One of the assumptions that impregnate academic discourse, even that of social scientists committed to the re-incorporation of their disciplines, is its extra-corporeal character. This article analyzes the scholastic construction of producing and perceiving oral, written or silent discourses as non-corporeal acts. First, it argues that there is a certain continuity between monastic rituals that build the spirit as something different from and higher than the body and academic rituals that train people to place the source of discourse in the mind. Second, it explores how the separation of discourse from the discourse-producing body is currently built and reproduced through participation in university and academic rituals. It holds that such participation installs in the bodies of academics an identification with the habit of producing discourses. Finally, it suggests that the fact that attempts to re-incorporate body to social life are performed by academics who have been trained in disembodying their discourses conditions the results of such attempts.
Beyond the Womb and the Tomb: Identity, (Dis)embodiment and the Life Course
Authors: Hockey Jenny , Draper Janet
Published: May 2005

Grounded in the authors’ theoretical and ethnographic work on pregnancy and social life after death, this article explores the ways in which the body is involved in processes of identification. With a focus on the embodied nature of social identity, the article nonetheless problematizes a model of the life course that begins at the moments of birth and ends at death. Instead, it offers a more extended temporal perspective and examines other ways in which identity may be claimed, for example, via material objects and practices which evoke the body as imagined or remembered. By documenting pre-birth and post-mortem identity-making of this kind, it demonstrates how the unborn and the dead may come into social existence. In addition, a cultural privileging of both the body and visuality is shown to shore up the capacity of material objects and practices to shape social identities in a highly selective fashion. The article therefore proposes that models of the life course need to accommodate the meanings of pre-birth and post-mortem materialities and so incorporate a conceptualization of social identity as contested, relational and inevitably incomplete.
Creating small schools in Chicago: an early look at implementation and impact
Authors: Kahne Joseph E. , Sporte Susan E. , Easton John Q.
Published: May 2005

There is widespread concern in many US cities about student alienation, dropout and under-achievement in large urban high schools. Chicago, with support from the Gates Foundation and other agencies, has embarked on a major reform involving the establishment of new small schools and the division of larger schools into smaller ones. This article reports on early evaluations of the project, alongside previous evaluations of small high schools. It highlights early effects such as: improved relationships; cooperation between teachers; awareness of personal difficulties; student engagement; and better attendance. Although it is too early to demonstrate the result in terms of summative attainment measures, these clearly provide a strong foundation.
Critical incidents in the working lives of a group of primary deputy heads
Authors: Kerry Trevor
Published: May 2005

This article uses small-scale research based on critical incident analysis to throw light on the importance of the role of the deputy head in primary schools. It suggests that deputies are frequently left alone and exposed to manage potentially very serious situations, and that both aspiring deputies and those new in post need specific training. The incidents recorded by deputies in the research indicate some areas for training, and also that reflection on critical incidents can help to improve performance. The need for more research and better training for deputy heads is driven by the trend towards devolved leadership in a context of school improvement. The article considers why a reflective approach using critical incidents is valuable as a learning tool.
‘Judgement day is coming!’: young people and the examination process in Scotland
Authors: Hamilton Lorna , Brown Jane
Published: May 2005

There is mounting evidence to suggest that the examination process is assuming greater importance in young people’s lives. Economic change has intensified demand for academic qualifications. An emphasis on viewing young people in terms of outcomes related to future identity and their success or failure within this context involves substantial pressure on pupil self esteem as a result of performance in high-stakes testing. Yet little is known about young people’s views about the examination process and what success or failure means from the perspective of pupils. This article draws on findings from a study focusing on the significance of exam taking from the perspective of pupils, parents and teachers living in Scotland. Drawing on interviews with pupils, teachers and a survey of parents in two Scottish high schools, we begin to explore the exam process and its impact upon the lives of young people, their families and school communities.
A linguistic toolbox for discourse analysis: towards a multidimensional handling of verbal interactions
Authors: Rouveyrol Laurent , Maury-Rouan Claire , Vion Robert , Noël-Jorand Marie-Christine
Published: May 2005

This article is aimed at introducing a French discourse analysis model, e.g. the ‘star model’, initiated by the LAA team led by Robert Vion in Aix-en-Provence, to English-speaking researchers. It will be argued that language activity is multi-dimensional and can be traced at various heterogeneous levels of speech productions belonging to macro as well as micro orders. Speakers achieve different varieties of positioning which result in negotiating an interactional space within a pre-given situation. The model is precisely designed to offer a unified and comprehensive view of such heterogeneous phenomena in constant interconnection. In this study, we also intend to illustrate our approach through the analysis of two different corpora. Speakers’ strategies under extreme conditions will be analysed; the various sequences used were taken from a special corpus which we were asked to study as part of a national research programme. In order to illustrate interactional space shifts, we will also use the transcript of a meeting which took place between a patient and a medical investigator in a hospital in Marseilles.
Constructing the source: metaphor as a discourse strategy
Authors: Wee Lionel
Published: May 2005

This article discusses various metaphorical texts where the authors construct or ‘make up’ their own sources. Such data contrast with the kinds of examples usually found in studies of metaphor, where the source is typically one that is ‘pre-given’. From a discourse perspective, it becomes interesting to ask under what circumstances a speaker/writer would attempt to create a brand new source instead of simply drawing upon pre-existing entities and events. The article shows that constructed sources tend to be used when the goal is the clarification of complex concepts. The complexity of the target concepts means that existing events and entities often lack the right structure that can easily be mapped onto the target, whereas the construction of their own sources allows the authors to have structures that are homologous with that of the target.
Damage Detection in Thin Plates and Aerospace Structures with the Electro-Mechanical Impedance Method
Authors: Giurgiutiu Victor , Zagrai Andrei
Published: May 2005

The use of the electro-mechanical (E/M) impedance method for health monitoring of thin plates and aerospace structures is described. As a nondestructive evaluation technology, the E/M impedance method allows us to identify the local dynamics of the structure directly through the E/M impedance signatures of piezoelectric wafer active sensors (PWAS) permanently mounted to the structure. An analytical model for 2-D thin-wall structures, which predicts the E/M impedance response at PWAS terminals, was developed and validated. The model accounts for axial and flexural vibrations of the structure and considers both the structural dynamics and the sensor dynamics. Calibration experiments performed on circular thin plates with centrally attached PWAS showed that the presence of damage modifies the high-frequency E/M impedance spectrum causing frequency shifts, peak splitting, and appearance of new harmonics. Overall-statistics damage metrics and probabilistic neural network (PNN) are used to classify the spectral data and identify damage severity. On thin-wall aircraft panels, the presence of damage influences the sensors E/M impedance spectrum. When crack damage is in the PWAS medium field, changes in the distribution of harmonics take place and when crack damage is in the PWAS near field, changes in both the harmonics and the dereverberated response are observed. These effects are successfully classified with PNN and overall-statistics metrics, respectively. This proves that permanently attached PWAS in conjunction with the E/M impedance method can be successfully used in structural health monitoring to detect the presence of incipient damage through the examination and classification of the high-frequency E/M impedance spectra.
Statistical Evaluation of Modified Electrical Resistance Change Method for Delamination Monitoring of CFRP Plate
Authors: Iwasaki Atsushi , Todoroki Akira
Published: May 2005

The present paper employs the electric resistance change method for monitoring the location and size of a delamination crack in graphite/epoxy composite laminates. The authors have revealed that the electric resistance change method with response surfaces is very effective experimentally and analytically. For the estimations of delamination locations, however, large error of the estimations still remains. FEM analyses revealed that the standardizations of the electric resistance changes are very effective to obtain high performance identifications. In this study, the new electric resistance change method of high performance identification of delaminations is applied to a plate-type specimen with an embedded delamination of cross-ply and quasi-isotropic laminates. Ten electrodes made from copper foil are mounted on the specimen top surfaces. The electric resistance changes are measured using a conventional strain gage amplifier. Response surfaces are adopted as a tool for solving inverse problems to estimate the location and size of delamination crack from the measured electric resistance changes of all segments between electrodes. Statistical analysis was performed to result of identification using the response surface. As a result, the present method successfully provides estimations of location and size of the embedded delamination for graphite/epoxy laminated composites.
Vibration-based Health Monitoring of Earth Structures
Authors: Mooney M. A. , Gorman P. B. , Gonzalez J. N.
Published: May 2005

Vibration-based health monitoring (VBHM) has successfully been used to assess the structural damage to bridges, buildings, aircraft, and rotating machinery. There is significant incentive to apply VBHM techniques to the damage detection and conditional assessment of earth structures (geostructures), e.g., foundations, dams, embankments, and tunnels, to improve design, construction, and performance. An experimental program was carried out to explore the efficacy of VBHM of earth structures. A vibratory roller compactor, instrumented with triaxial accelerometers to continuously measure drum and frame vibrations, was operated on a number of underlying material structures with varying properties. Time-domain and frequency-domain analyses of the coupled machine/earth structure response were performed to glean machine vibration features that reflect changes in underlying structural properties. Results illustrate that drum and frame acceleration amplitudes were fairly insensitive to changes in underlying media stiffness; however, drum acceleration frequency components (harmonics) were found to be sensitive to changes in underlying media and changes in soil properties during compaction. The strata underlying the soil undergoing compaction was found to strongly affect drum vibration characteristics.
A Wavelet Packet Based Sifting Process and its Application for Structural Health Monitoring
Authors: Shinde Abhijeet , Hou Zhikun
Published: May 2005

This article presents an innovative wavelet packet based sifting process to decompose a signal into its components with different frequency contents by examining the energy content in the wavelet packet components of a signal and imposing certain decomposition criteria. A new method is illustrated for simulation data of a linear three-degree-of-freedom spring-mass-damper system and the results are compared with those obtained using the empirical mode decomposition (EMD) method. Both methods provide good approximations, as compared with the exact solution for modal responses from a conventional modal analysis and both show relatively greater errors at the beginning and ending parts of the signal due to the well-known end effects. A comparison study is also provided to illustrate differences between two sifting processes of the proposed approach and the EMD, by using a harmonic signal with a sweeping frequency and the impulse response of a linear single-degree-of-freedom system with viscous damping. Incorporated with the classical Hilbert transform, the proposed sifting process may be effectively used for structural health monitoring, including both detecting abrupt loss of structural stiffness and monitoring development of progressive stiffness degradation, as demonstrated by two case studies. Results from a preliminary study for experimental data from a shaking table test of a full-size two-story wooden building structure are also presented to show great promise of the proposed method in practical applications of health monitoring of real structures.
Structural Damage Identification in Homogeneous and Heterogeneous Structures Using Beamforming
Authors: Sundararaman Shankar , Adams Douglas E. , Rigas Elias J.
Published: May 2005

In this study, beamformers consisting of phased sensor or actuator arrays are used in the nondestructive evaluation of homogeneous and heterogeneous structural components. Beamforming can be used to detect, locate, and quantify damage by suitably applying weights and time or phase delays to the tapped signals from a sensor array and/or actuator array in a narrow frequency band to obtain the desired directional sensitivities and optimal array gains. Some aspects about beamforming and wave propagation are discussed as a prelude to the experimental investigation. Design considerations for the phased arrays are also examined. The advantages of using adaptive over conventional beamforming are demonstrated with Frost constraint- and pilot signal-based adaptive techniques. Data from steel and composite plates are analyzed using propagating elastic waves and phased arrays of sensors and/or actuators. Damage, which can be characterized as a local change in impedance, is diagnosed by using propagating elastic waves as they are sensitive to small changes in impedance and do not require a large number of input/output transducers. Beamforming of sensor and/or actuator arrays is carried out to characterize damage in steel and composite plates by comparing the directivity patterns associated with the damage and baseline data.
Expressivism, Deflationism and Correspondence
Authors: Marino Patricia
Published: May 2005

On an expressivist view, ethical claims are not fact stating; instead they serve the alternative function of expressing our feelings, attitudes and values. On a deflationary view, truth is not a property with a nature to be analyzed, but merely a grammatical device to aid us in endorsing sentences. Views on the relationship between expressivism and deflationism vary widely: they are compatible; they are incompatible; they are a natural pair; they doom one another. Here I explain some of these views, extract some necessary distinctions, and put these to use for understanding expressivism. I argue that contrary to the opinions of some, deflationism doesn’t help with problems of objectivity, knowledge and reasoning in ethics. I suggest alternative expressivist treatments of these problems, and show how expressivism as a metaethical view must have consequences for our ethical lives and beliefs. In particular it must affect the way we deal with ethical consistency—when norms or beliefs conflict—and ethical incompleteness—when ethical questions have no right answer.
Virtue for Pluralists
Authors: Sabl Andrew
Published: May 2005

Liberal or democratic virtue theories have successfully spread the idea that liberal democracies cannot flourish unless their citizens have certain qualities of mind and character. Such theories cannot agree, however, on what those qualities are. This article attempts to explain and solve this problem. It proposes distinguishing between core virtues, necessary for the actual survival of liberal democracies, and ideal virtues, which promote “progress” according to a given conception of what liberal democracies ought to be about and which values they should most embody. Beyond this, it portrays the relevant virtues as pluralistic (not everyone need have the same ones) and episodic (different virtues are relevant at different times and under different circumstances). It then applies this framework to some key issues of political action and motivation: acts of loyalty and dissent express different aspects of a common response to moral pluralism, and the virtues of citizens differ fundamentally in origin and nature from those of professional politicians. Finally, it suggests more briefly that questions of civil religion, patriotic mobilization in times of war, civic courage, and selfish versus altruistic motives for public action can profit from being seen in this new way.
GPVI and α2β1 play independent critical roles during platelet adhesion and aggregate formation to collagen under flow
Authors: Sarratt Kendra L. , Chen Hong , Zutter Mary M. , Santoro Samuel A. , Hammer Daniel A. , Kahn Mark L.
Published: May 2005

The roles of the 2 major platelet-collagen receptors, glycoprotein VI (GPVI) and integrin α2β1, have been intensely investigated using a variety of methods over the past decade. In the present study, we have used pharmacologic and genetic approaches to study human and mouse platelet adhesion to collagen under flow conditions. Our studies demonstrate that both GPVI and integrin α2β1 play significant roles for platelet adhesion to collagen under flow and that the loss of both receptors completely ablates this response. Intracellular signaling mediated by the cytoplasmic adaptor Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76) but not by the transmembrane adaptor linker for activation of T cells (LAT) is critical for platelet adhesion to collagen under flow. In addition, reduced GPVI receptor density results in severe defects in platelet adhesion to collagen under flow. Defective adhesion to collagen under flow is associated with prolonged tail-bleeding times in mice lacking one or both collagen receptors. These studies establish platelet-collagen responses under physiologic flow as the consequence of a close partnership between 2 structurally distinct receptors and suggest that both receptors play significant hemostatic roles in vivo.
A SCID-hu in vivo model of human Waldenström macroglobulinemia
Authors: Tassone Pierfrancesco , Neri Paola , Kutok Jeffery L. , Tournilhac Olivier , Santos Daniel Ditzel , Hatjiharissi Evdoxia , Munshi Vidit , Venuta Salvatore , Anderson Kenneth C. , Treon Steven P. , Munshi Nikhil C.
Published: May 2005

The preclinical evaluation of investigational agents for Waldenström macroglobulinemia (WM) has been limited by the lack of in vivo models that enable the use of explanted patient cells. We describe here a novel in vivo model of human WM in severe combined immunodeficient (SCID) mice implanted with human fetal bone chips (SCID-hu mice) into which WM cells from patient bone marrow are engrafted directly into the human bone marrow (huBM) microenvironment. WM cells in SCID-hu mice produced human monoclonal paraprotein (immunoglobulin M [IgM] and/or κ or λ chain) detectable in mice sera. Immunohistochemical analysis of human bone retrieved from SCID-hu mice showed infiltration with CD20+, IgM+, and monotypic light chain+ lymphoplasmacytic cells. Mast cells were observed to be associated with the infiltrate in these sections. Treatment of SCID-hu mice bearing WM with rituximab induced tumor regression, associated with a decrease in serum paraprotein. This model, therefore, recapitulates the in vivo biology of WM and allows the study of novel investigational drugs targeting WM cells in the huBM milieu. (Blood. 2005;106:1341-1345)
Altered NKG2D function in NK cells induced by chronic exposure to NKG2D ligand–expressing tumor cells
Authors: Coudert Jérôme D. , Zimmer Jacques , Tomasello Elena , Cebecauer Marek , Colonna Marco , Vivier Eric , Held Werner
Published: May 2005

NKG2D is an activation receptor that allows natural killer (NK) cells to detect diseased host cells. The engagement of NKG2D with corresponding ligand results in surface modulation of the receptor and reduced function upon subsequent receptor engagement. However, it is not clear whether in addition to modulation the NKG2D receptor complex and/or its signaling capacity is preserved. We show here that the prolonged encounter with tumor cell-bound, but not soluble, ligand can completely uncouple the NKG2D receptor from the intracellular mobilization of calcium and the exertion of cell-mediated cytolysis. However, cytolytic effector function is intact since NKG2D ligand-exposed NK cells can be activated via the Ly49D receptor. While NKG2D-dependent cytotoxicity is impaired, prolonged ligand exposure results in constitutive interferon γ (IFNγ) production, suggesting sustained signaling. The functional changes are associated with a reduced presence of the relevant signal transducing adaptors DNAX-activating protein of 10 kDa (DAP-10) and killer cell activating receptor-associated protein/DNAX-activating protein of 12 kDa (KARAP/DAP-12). That is likely the consequence of constitutive NKG2D engagement and signaling, since NKG2D function and adaptor expression is restored to normal when the stimulating tumor cells are removed. Thus, the chronic exposure to tumor cells expressing NKG2D ligand alters NKG2D signaling and may facilitate the evasion of tumor cells from NK cell reactions. (Blood. 2005;106:1711-1717)
Neutrophils rapidly migrate via lymphatics after Mycobacterium bovis BCG intradermal vaccination and shuttle live bacilli to the draining lymph nodes
Authors: Abadie Valérie , Badell Edgar , Douillard Patrice , Ensergueix Danielle , Leenen Pieter J. M. , Tanguy Myriam , Fiette Laurence , Saeland Sem , Gicquel Brigitte , Winter Nathalie
Published: May 2005

The early innate response after Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination is poorly characterized but probably decisive for subsequent protective immunity against tuberculosis. Therefore, we vaccinated mice with fluorescent BCG strains in the ear dorsum, as a surrogate of intradermal vaccination in humans. During the first 3 days, we tracked BCG host cells migrating out of the dermis to the auricular draining lymph nodes (ADLNs). Resident skin dendritic cells (DCs) or macrophages did not play a predominant role in early BCG capture and transport to ADLNs. The main BCG host cells rapidly recruited both in the dermis and ADLNs were neutrophils. Fluorescent green or red BCG strains injected into nonoverlapping sites were essentially sheltered by distinct neutrophils in the ADLN capsule, indicating that neutrophils had captured bacilli in peripheral tissue and transported them to the lymphoid organ. Strikingly, we observed BCG-infected neutrophils in the lumen of lymphatic vessels by confocal microscopy on ear dermis. Fluorescence-labeled neutrophils injected into the ears accumulated exclusively into the ipsilateral ADLN capsule after BCG vaccination. Thus, we provide in vivo evidence that neutrophils, like DCs or inflammatory monocytes, migrate via afferent lymphatics to lymphoid tissue and can shuttle live microorganisms. (Blood. 2005;106: 1843-1850)
Pigs in sequence space: A 0.66X coverage pig genome survey based on shotgun sequencing
Authors: Wernersson Rasmus , Schierup Mikkel H , Jørgensen Frank G , Gorodkin Jan , Panitz Frank , Stærfeldt Hans-Henrik , Christensen Ole F , Mailund Thomas , Hornshøj Henrik , Klein Ami , Wang Jun , Liu Bin , Hu Songnian , Dong Wei , Li Wei , Wong Gane KS , Yu Jun , Wang Jian , Bendixen Christian , Fredholm Merete , Brunak Søren , Yang Huanming , Bolund Lars
Published: May 2005

Background

Comparative whole genome analysis of Mammalia can benefit from the addition of more species. The pig is an obvious choice due to its economic and medical importance as well as its evolutionary position in the artiodactyls.

Results

We have generated ~3.84 million shotgun sequences (0.66X coverage) from the pig genome. The data are hereby released (NCBI Trace repository with center name "SDJVP", and project name "Sino-Danish Pig Genome Project") together with an initial evolutionary analysis.

The non-repetitive fraction of the sequences was aligned to the UCSC human-mouse alignment and the resulting three-species alignments were annotated using the human genome annotation. Ultra-conserved elements and miRNAs were identified. The results show that for each of these types of orthologous data, pig is much closer to human than mouse is. Purifying selection has been more efficient in pig compared to human, but not as efficient as in mouse, and pig seems to have an isochore structure most similar to the structure in human.

Conclusion

The addition of the pig to the set of species sequenced at low coverage adds to the understanding of selective pressures that have acted on the human genome by bisecting the evolutionary branch between human and mouse with the mouse branch being approximately 3 times as long as the human branch. Additionally, the joint alignment of the shot-gun sequences to the human-mouse alignment offers the investigator a rapid way to defining specific regions for analysis and resequencing.
A study of inter-lab and inter-platform agreement of DNA microarray data
Authors: Wang Huixia , He Xuming , Band Mark , Wilson Carole , Liu Lei
Published: May 2005

As gene expression profile data from DNA microarrays accumulate rapidly, there is a natural need to compare data across labs and platforms. Comparisons of microarray data can be quite challenging due to data complexity and variability. Different labs may adopt different technology platforms. One may ask about the degree of agreement we can expect from different labs and different platforms. To address this question, we conducted a study of inter-lab and inter-platform agreement of microarray data across three platforms and three labs. The statistical measures of consistency and agreement used in this paper are the Pearson correlation, intraclass correlation, kappa coefficients, and a measure of intra-transcript correlation. The three platforms used in the present paper were Affymetrix GeneChip, custom cDNA arrays, and custom oligo arrays. Using the within-platform variability as a benchmark, we found that these technology platforms exhibited an acceptable level of agreement, but the agreement between two technologies within the same lab was greater than that between two labs using the same technology. The consistency of replicates in each experiment varies from lab to lab. When there is high consistency among replicates, different technologies show good agreement within and across labs using the same RNA samples. On the other hand, the lab effect, especially when confounded with the RNA sample effect, plays a bigger role than the platform effect on data agreement.
Using the ecology model to describe the impact of asthma on patterns of health care
Authors: Yawn Barbara P , Fryer George E , Phillips Robert L , Dovey Susan M , Lanier David , Green Larry A
Published: May 2005

Background

Asthma changes both the volume and patterns of healthcare of affected people. Most studies of asthma health care utilization have been done in selected insured populations or in a single site such as the emergency department. Asthma is an ambulatory sensitive care condition making it important to understand the relationship between care in all sites across the health service spectrum. Asthma is also more common in people with fewer economic resources making it important to include people across all types of insurance and no insurance categories. The ecology of medical care model may provide a useful framework to describe the use of health services in people with asthma compared to those without asthma and identify subgroups with apparent gaps in care.

Methods

This is a case-control study using the 1999 U.S. Medical Expenditure Panel Survey. Cases are school-aged children (6 to 17 years) and young adults (18 to 44 years) with self-reported asthma. Controls are from the same age groups who have no self-reported asthma. Descriptive analyses and risk ratios are placed within the ecology of medical care model and used to describe and compare the healthcare contact of cases and controls across multiple settings.

Results

In 1999, the presence of asthma significantly increased the likelihood of an ambulatory care visit by 20 to 30% and more than doubled the likelihood of making one or more visits to the emergency department (ED). Yet, 18.8% of children and 14.5% of adults with asthma (over a million Americans) had no ambulatory care visits for asthma. About one in 20 to 35 people with asthma (5.2% of children and 3.6% of adults) were seen in the ED or hospital but had no prior or follow-up ambulatory care visits. These Americans were more likely to be uninsured, have no usual source of care and live in metropolitan areas.

Conclusion

The ecology model confirmed that having asthma changes the likelihood and pattern of care for Americans. More importantly, the ecology model identified a subgroup with asthma who sought only emergent or hospital services.
Java Web Start based software for automated quantitative nuclear analysis of prostate cancer and benign prostate hyperplasia
Authors: Singh Swaroop S , Kim Desok , Mohler James L
Published: May 2005

Background

Androgen acts via androgen receptor (AR) and accurate measurement of the levels of AR protein expression is critical for prostate research. The expression of AR in paired specimens of benign prostate and prostate cancer from 20 African and 20 Caucasian Americans was compared to demonstrate an application of this system.

Methods

A set of 200 immunopositive and 200 immunonegative nuclei were collected from the images using a macro developed in Image Pro Plus. Linear Discriminant and Logistic Regression analyses were performed on the data to generate classification coefficients. Classification coefficients render the automated image analysis software independent of the type of immunostaining or image acquisition system used. The image analysis software performs local segmentation and uses nuclear shape and size to detect prostatic epithelial nuclei. AR expression is described by (a) percentage of immunopositive nuclei; (b) percentage of immunopositive nuclear area; and (c) intensity of AR expression among immunopositive nuclei or areas.

Results

The percent positive nuclei and percent nuclear area were similar by race in both benign prostate hyperplasia and prostate cancer. In prostate cancer epithelial nuclei, African Americans exhibited 38% higher levels of AR immunostaining than Caucasian Americans (two sided Student's t-tests; P < 0.05). Intensity of AR immunostaining was similar between races in benign prostate.

Conclusion

The differences measured in the intensity of AR expression in prostate cancer were consistent with previous studies. Classification coefficients are required due to non-standardized immunostaining and image collection methods across medical institutions and research laboratories and helps customize the software for the specimen under study. The availability of a free, automated system creates new opportunities for testing, evaluation and use of this image analysis system by many research groups who study nuclear protein expression.
Predicting Inhibitory Drug—Drug Interactions and Evaluating Drug Interaction Reports Using Inhibition Constants
Authors: Bachmann Kenneth A , Lewis Jeffrey D
Published: May 2005

OBJECTIVE:

To review the use of inhibitory constants (Ki) determined from in vitro experiments in the prediction of the significance of inhibitory drug—drug interactions (DDIs).

DATA SOURCES:

Searches of MEDLINE (1966—August 2004) and manual review of journals, conference proceedings, reference textbooks, and Web sites were performed using the key search terms cytochrome P450, drug—drug interaction, inhibition constant, and Ki.

STUDY SELECTION AND DATA EXTRACTION:

All articles identified from the data sources were evaluated, and information deemed relevant was included for this review.

DATA SYNTHESIS:

The cytochrome P450 isoenzymes factor prominently in the explanation of numerous DDIs. Although the regulation of these enzymes by one drug can affect the pharmacokinetics of other drugs, the consequences may not necessarily be significant either in terms of pharmacokinetic or clinical outcomes. Yet, many DDI monographs originate as unconfirmed case reports that implicate the influence of one drug on the CYP-mediated metabolism of another, and these often uncorroborated mechanisms can eventually become regarded as dogma. One consequence of this process is the overprediction of potentially important DDIs. The pharmaceutical industry, Food and Drug Administration, and pharmaceutical scientists have developed a strategy for predicting the significance of inhibitory DDIs at the earliest possible stages of drug development based on a new chemical entity's Ki value, determined in vitro.

CONCLUSIONS:

We suggest that the use of Ki values of drugs purported to behave as CYP inhibitors be incorporated in the assessment of case reports that ascribe DDIs to inhibition of metabolism of one drug by another.
Phenazopyridine-Induced Sulfhemoglobinemia
Authors: Gopalachar Anuradha S , Bowie Venita L , Bharadwaj Parag
Published: May 2005

OBJECTIVE:

To report a case of sulfhemoglobinemia in a patient receiving phenazopyridine for a urinary tract infection.

CASE SUMMARY:

A 63-year-old white woman presented to the emergency department with complaints of fatigue and bluish discoloration of her body that had gradually progressed over the previous 6–8 weeks. About 4 months prior to presenting to the emergency department, she had started taking phenazopyridine, an over-the-counter medication for symptoms of dysuria. Because the cyanosis did not improve after the patient received oxygen and methylene blue, sulfhemoglobinemia was suspected and confirmed by spectrophotometer analysis.

DISCUSSION:

Sulfhemoglobin is a green-pigmented molecule containing a sulfur atom in one or more of the porphyrin rings. It is a rare cause of cyanosis, which is usually drug induced. Sulfhemoglobinemia is suspected when a cyanotic patient has normal to near-normal oxygen tension, laboratory reports of elevated methemoglobin, and does not respond to methylene blue therapy. Sulfhemoglobinemia is relatively rare, despite the widespread use of drugs that have been reported to cause it. Predisposing factors, such as chronic constipation, present in our patient, have been suggested as a source of hydrogen sulfide.

CONCLUSIONS:

This case of sulfhemoglobinemia, which occurred after the patient took phenazopyridine, is considered a probable adverse event according to the Naranjo probability scale.