bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Novel Polyimide Hollow‐fiber Oxygenator
Authors: Niwa Motohiro , Kawakami Hiroyoshi , Nagaoka Shoji , Kanamori Toshiyuki , Morisaku Kazuko , Shinbo Toshio , Matsuda Toshiaki , Sakai Kazunari , Kubota Sunao
Published: April 2004

Abstract:  We have developed a membrane oxygenator using a novel asymmetric polyimide hollow fiber. The hollow fibers are prepared using a dry/wet phase‐inversion process. The gas transfer rates of O2 and CO2 through the hollow fibers are investigated in gas–gas and gas–liquid systems. The polyimide hollow fiber has an asymmetric structure characterized by the presence of macrovoids, and the outer diameter of the hollow fiber is 330 µm. It is found that the polyimide hollow‐fiber oxygenator can enhance the gas transfer rates of O2 and CO2, and that the hollow fiber provides excellent blood compatibility in vitro and in vivo.
Alginate‐encapsulated Human Hepatoblastoma Cells in an Extracorporeal Perfusion System Improve Some Systemic Parameters of Liver Failure in a Xenogeneic Model
Authors: Rahman Tony M. , Selden Clare , Khalil Marianne , Diakanov Ivan , Hodgson Humphrey J.F.
Published: April 2004

Abstract:  Previous studies have demonstrated that alginate encapsulation of proliferating hepatocyte‐derived cell lines (e.g., HepG2 cells) enhances the expression of differentiated hepatocyte function compared with conventional monolayer culture. Furthermore, such capsules have the advantage of cryopreservability, and can be readily manip‐ulated,  e.g.,  for  the  charging  of  extracorporeal devices.  We utilize a rabbit model of acute liver failure caused by acetaminophen administration to rabbits pretreated to enhance cytochrome P450 enzyme activity, and demonstrate that encapsulated HepG2 cells, in an extracorporeal chamber, perfused by rabbit plasma separated on‐line at a rate of 2–5 mL/min, and perfused over cells at 40–60 mL/min, improve systemic parameters of liver failure (diastolic blood pressure and transjugular venous oxygen saturation). Such encapsulated cells have the potential to be developed for extracorporeal liver support systems for acute liver failure.
Particle Image Velocimetry for Flow Analysis in Longitudinal Planes across a Mechanical Artificial Heart Valve
Authors: Castellini Paolo , Pinotti Marcos , Scalise Lorenzo
Published: April 2004

Abstract:  In the last decades a great number of in vitro studies have been conducted to improve the design and to understand the transvalvular flow patterns under steady‐state and pulsating flow conditions. Steady‐state tests are useful for studying the flow established upstream and downstream of the valve prosthesis in different flow conditions and, in particular, at the peak flow rate. In the present study, the particle image velocimetry (PIV) technique is employed to visualize the flow patterns in a precommercial model of a bi‐leaflet mechanical heart valve prosthesis in a steady‐state flow regime. The use of the PIV technique and a convenient test rig provide good conditions with which to investigate the whole flow field upstream and downstream of the valve. Velocity and vorticity maps are obtained for the flow passing through the prosthesis in different axial planes. A new and simple solution for the measurement test chamber is proposed. This innovative approach of observing the flow in staggered planes (other than diametrical planes) allows a flow analysis to be performed upstream and downstream of the valve in regions near the tube wall where it has the maximum potential for injury of the vessel's inner cell layer.
What's the Use of Philosophy? Democratic Citizenship and the Direction of Higher Education
Authors: Altman Matthew C.
Published: April 2004

In order to justify the discipline to administrators and prospective majors, many philosophy departments have begun to emphasize the "transferable skills" that students can develop in their courses — problem‐solving and communication skills, the ability to argue and write well, and the capacity to engage in systematic analysis. However, designing the study of philosophy around job preparation reinforces a particular conception of the good life and undermines philosophy's primary goal: to invite us to question the values we already hold and to ask whether those values should govern our lives. Philosophers should encourage students' capacity to question conventional norms and to engage in the rational pursuit of the good life. Education then becomes a social activity of holding ourselves to certain values. This shift in subject matter and teaching methods will serve the larger political purpose of better preparing students to be democratic citizens who are able to participate in public dialogue about questions of justice and morality.
Autocrine feedback inhibition of plateau potentials terminates phasic bursts in magnocellular neurosecretory cells of the rat supraoptic nucleus
Authors: Brown Colin H. , Bourque Charles W.
Published: April 2004

Phasic activity in magnocellular neurosecretory cells is characterized by alternating periods of activity (bursts) and silence. During phasic bursts, action potentials are superimposed on plateau potentials that are generated by summation of depolarizing after‐potentials. Dynorphin is copackaged in vasopressin neurosecretory vesicles that are exocytosed from magnocellular neurosecretory cell dendrites and terminals, and both peptides have been implicated in the generation of phasic activity. Here we show that somato‐dendritic dynorphin release terminates phasic bursts by autocrine inhibition of plateau potentials in magnocellular neurosecretory cells recorded intracellularly from hypothalamic explants using sharp electrodes. Conditioning spike trains caused an activity‐dependent reduction of depolarizing after‐potential amplitude that was partially reversed by α‐latrotoxin (which depletes neurosecretory vesicles) and by nor‐binaltorphimine (κ‐opioid receptor antagonist), but not by an oxytocin/vasopressin receptor antagonist or a μ‐opioid receptor antagonist, indicating that activity‐dependent inhibition of depolarizing after‐potentials requires exocytosis of an endogenous κ‐opioid peptide. κ‐Opioid inhibition of depolarizing after‐potentials was not mediated by actions on evoked after‐hyperpolarizations since these were not affected by κ‐opioid receptor agonists or antagonists. Evoked bursts were prolonged by antagonism of κ‐opioid receptors with nor‐binaltorphimine and by depletion of neurosecretory vesicles by α‐latrotoxin, becoming everlasting in ∼50% of cells. Finally, spontaneously active neurones exposed to nor‐binaltorphimine switched from phasic to continuous firing as plateau potentials became non‐inactivating. Thus, dynorphin coreleased with vasopressin generates phasic activity through activity‐dependent feedback inhibition of plateau potentials in magnocellular neurosecretory cells.
Acute myeloid leukaemia presenting as cholestatic hepatitis
Authors: Wandroo F A , Murray J , Mutimer D , Hubscher S
Published: April 2004

A 40 year old man presented with abdominal pain, jaundice, weight loss, and hepatosplenomegaly. Liver function tests revealed cholestatic jaundice and a computed tomography scan showed an enlarged liver, with a normal biliary tree. Liver biopsy showed diffuse infiltration by neutrophils, monocytoid cells, and blasts. Peripheral blood film and bone marrow were consistent with acute myeloid leukaemia. After treatment with chemotherapy using an acute myeloid leukaemia protocol (UK Medical Research Council AML-12), there was complete resolution of jaundice and the patient went into complete molecular remission.
Evidence that protease activated receptor 2 expression is enhanced in human coronary atherosclerotic lesions
Authors: Napoli C , de Nigris F , Wallace J L , Hollenberg M D , Tajana G , De Rosa G , Sica V , Cirino G
Published: April 2004

Aim:To investigate protease activated receptor 2 (PAR-2) expression in human coronary atherosclerotic lesions because PAR-2 is involved in the modulation of inflammatory events and vascular function.

Methods:An immunohistochemical analysis was performed on serial arterial sections, using the following antibodies: MDA2, a murine monoclonal antibody against malondialdehyde lysine epitopes of oxidised low density lipoprotein (oxLDL); HAM-56, a monoclonal antibody against human macrophages/foam cells; B5, a rabbit polyclonal antibody against PAR-2; and SAM11, a mouse monoclonal antibody against human PAR-2. Sections containing at least one lesion showing substantial immunostaining were counted as positive, and results were expressed as per cent of all sections of the same artery.

Results:PAR-2 expression was enhanced in human coronary atherosclerotic lesions. This phenomenon correlated with an increase in oxLDL epitopes in the coronary artery.

Conclusion:This study shows for the first time that PAR-2 expression is enhanced in human coronary atherosclerotic lesions, and suggests that PAR-2 dependent cellular trafficking may be one of the regulatory signalling responses to vascular injury. Further pharmacological studies will establish whether modulation (and in which direction) of PAR-2 represents a possible therapeutic target for controlling the vascular response to injury.
Sudden death of a patient with primary hypereosinophilia, colon tumours, and pulmonary emboli
Authors: Uemura K , Nakajima M , Yamauchi N , Fukayama M , Yoshida K
Published: April 2004

A 33 year old man was admitted to hospital six days after the onset of abdominal pain. There was hypereosinophilia, but the cause could not be identified (primary hypereosinophilia). The hypereosinophilia, high C reactive protein concentration, and gastrointestinal symptoms were alleviated by corticosteroid treatment. Unexpectedly, after this apparent recovery, he was found dead on the 27th day after admission. Necropsy disclosed two solid tumours primarily composed of eosinophils in the ascending and transverse colon. The cause of the sudden death was pulmonary artery emboli, derived from a thrombus in the left iliac vein.
NOISE ANALYSIS IN STUDIES OF PROTEIN DYNAMICS AND MOLECULAR TRANSPORT
Authors: BEZRUKOV SERGEY M.
Published: April 2004

Understanding the role of noise at cellular and higher hierarchical levels depends on our knowledge of the physical mechanisms of its generation. Conversely, noise is a rich source of information about these mechanisms. Using channel-forming protein molecules reconstituted into artificial 5-nm-thick insulating lipid films, it is possible to investigate noise in single-molecule experiments and to relate its origins to protein function. Recent progress in this field is reviewed with an emphasis on how this experimental technique can be used to study low-frequency protein dynamics, including not only reversible ionization of sites on the channel-forming protein molecule, but also molecular mechanisms of 1/f-noise generation. Several new applications of the single-molecule noise analysis to membrane transport problem are also addressed. Among those is a study on antibiotic translocation across bacterial walls. High-resolution recording of ionic current through the single channel, formed by the general bacterial porin, OmpF, enables us to resolve single-molecule events of antibiotic translocation.
Recovery of Cortical Binocularity and Orientation Selectivity After the Critical Period for Ocular Dominance Plasticity
Authors: Liao David S. , Krahe Thomas E. , Prusky Glen T. , Medina Alexandre E. , Ramoa Ary S.
Published: April 2004

Cortical binocularity is abolished by monocular deprivation (MD) during a critical period of development lasting from approximately postnatal day (P) 35 to P70 in ferrets. Although this is one of the best-characterized models of neural plasticity and amblyopia, very few studies have examined the requirements for recovery of cortical binocularity and orientation selectivity of deprived eye responses. Recent studies indicating that different mechanisms regulate loss and recovery of binocularity raise the possibility that different sensitive periods characterize loss and recovery of deprived eye responses. In this report, we have examined whether the potential for recovery of binocularity and orientation selectivity is restricted to the critical period. Quantitative single unit recordings revealed recovery of cortical binocularity and full recovery of orientation selectivity of deprived eye responses following prolonged periods of MD (i.e., >3 wk) starting at P49, near the peak of plasticity. Surprisingly, recovery was present when binocular vision was restored after the end of the critical period for ocular dominance plasticity, as late as P83. In contrast, ferrets that had never received visual experience through the deprived eye failed to recover binocularity even though normal binocular vision was restored at P50, halfway through the critical period. Collectively, these results indicate that there is potential for recovery of cortical binocularity and deprived eye orientation selectivity after the end of the critical period for ocular dominance plasticity.
Sympathetic Drive in Anterior and Inferior Uncomplicated Acute Myocardial Infarction
Authors: Graham Lee N. , Smith Paul A. , Huggett Robert J. , Stoker John B. , Mackintosh Alan F. , Mary David A.S.G.
Published: April 2004

Background—

The sympathetic activation that follows acute myocardial infarction (AMI) has been associated with increased morbidity and mortality. Because the prognosis after anterior AMI (ant-AMI) is worse than that after inferior AMI (inf-AMI), we planned to determine whether the magnitude of sympathetic hyperactivity differs between the two.

Methods and Results—

Thirty-nine patients with uncomplicated AMI, comprising 2 matched groups of 17 patients with ant-AMI, and 22 patients with inf-AMI were examined. Measurements were obtained 2 to 4 days after AMI and compared with 20 normal subjects (NC) who were matched in terms of age and body weight to the AMI groups. Resting muscle sympathetic nerve activity was quantified from multiunit bursts (MSNA) and from single units (s-MSNA). Both groups of AMI patients were matched with regard to hemodynamic variables, left ventricular function, and infarct size. Both groups had greater (at least
P
<0.01) sympathetic nerve activity than NC (60±4.3 bursts/100 cardiac beats and 68±4.9 impulses/100 cardiac beats), but the magnitude of sympathetic nerve hyperactivity in ant-AMI (81±4.0 bursts/100 cardiac beats and 91±4.9 impulses/100 cardiac beats) was similar (
P
>0.05) to that in inf-AMI (80±3.2 bursts/100 cardiac beats and 90±4.0 impulses/100 cardiac beats)

Conclusions—

Both ant-AMI and inf-AMI resulted primarily in a similar magnitude of sympathetic nerve hyperactivity. These findings suggest that the worse prognosis after ant-AMI compared with after inf-AMI would not be related primarily to the degree of sympathetic hyperactivity.
Blood Pressure Control and Physician Management of Hypertension in Hospital Hypertension Units in Spain
Authors: Banegas José R. , Segura Julián , Ruilope Luis M. , Luque Manuel , García-Robles Rafael , Campo Carlos , Rodríguez-Artalejo Fernando , Tamargo Juan
Published: April 2004

Goal blood pressure (BP) was defined by the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) and the World Health Organization–International Society of Hypertension (WHO/ISH) as <140 mm Hg systolic and <90 mm Hg diastolic for the general and <130 mm Hg systolic and <85 mm Hg diastolic for special high-risk populations. However, there are few reports that address BP control among special subgroups of hypertensives by reference to targeted BP. We therefore conducted a study to evaluate BP control of 4049 hypertensives in 47 hospital-based hypertension units in Spain. Overall, 42% of patients achieved goal BP (<140 mm Hg systolic and <90 mm Hg diastolic). Only 13% of diabetic patients and 17% of those with renal disease achieved the BP goal (<130 mm Hg systolic and <85 mm Hg diastolic), and only 10% and 12%, respectively, achieved the even more rigorous goal (<130 mm Hg systolic and <80 mm Hg diastolic). Likewise, only 18% of patients in JNC-VI risk group C and 17% of WHO/ISH high-risk patients attained a goal BP <130 mm Hg systolic and <85 mm Hg diastolic. BP control (<125 mm Hg systolic and <75 mm Hg diastolic) was extremely low (2%) in patients with proteinuria >1 g/d. Poorer BP control was observed among patients at high risk, with diabetes, renal disease, or obesity, than in lower-risk groups. BP control was lower for systolic than for diastolic BP. In >50% of uncontrolled patients, no measures were taken by doctors to optimize pharmacologic treatment, and approximately one-third of patients were still using drug monotherapy. Control of BP, particularly of systolic BP, is still far from optimal in hospital-based hypertension units. Patients at high risk, with diabetes or proteinuria, warrant focused attention. Moreover, a more aggressive behavior of doctors treating uncontrolled hypertension is needed.
Eplerenone Prevents Salt-Induced Vascular Remodeling and Cardiac Fibrosis in Stroke-Prone Spontaneously Hypertensive Rats
Authors: Endemann Dierk H. , Touyz Rhian M. , Iglarz Marc , Savoia Carmine , Schiffrin Ernesto L.
Published: April 2004

We examined the effect of different levels of salt intake on the role of aldosterone on cardiac and vascular changes in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Eleven-week-old SHRSP were fed high-salt (4.2% NaCl), normal-salt (0.28%), or low-salt (0.03%) diets with or without eplerenone (100 mg/kg per day, in food) for 5 weeks. A group of high-salt SHRSP was also treated with hydralazine (25 mg/kg per day). Blood pressure increased more in high-salt rats than in other groups (
P
<0.001). Eplerenone prevented further blood pressure rise in salt-loaded rats, with little effect on control and low-salt SHRSP. Increased media-to-lumen ratio of mesenteric resistance arteries induced by salt (
P
<0.01) was prevented by eplerenone (
P
<0.01). Maximal acetylcholine-induced vasodilation was impaired under salt loading (
P
<0.01), but improved under eplerenone (
P
<0.01). Eplerenone prevented (
P
<0.01) increased heart weight and left and right ventricular collagen deposition induced by high salt. Blood pressure lowering by hydralazine in high-salt SHRSP did not influence endothelial function or left ventricular collagen. Our study demonstrates salt-dependency of aldosterone effects on severity of hypertension, endothelial dysfunction, and cardiac and vascular remodeling in SHRSP. These effects were attenuated by eplerenone, particularly in the salt-loaded state, underlining the pathophysiological role of aldosterone in salt-sensitive hypertension.
Early Fibrinogen Degradation Coagulopathy Is Predictive of Parenchymal Hematomas in Cerebral rt-PA Thrombolysis
Authors: Trouillas Paul , Derex Laurent , Philippeau Fréderic , Nighoghossian Norbert , Honnorat Jerome , Hanss Micel , Ffrench Patrick , Adeleine Patrice , Dechavanne Marc
Published: April 2004

Background—

Little is known about the coagulation factors as predictors of cerebral bleeding in rt-PA thrombolysis. The aim of this study was to determine what early coagulation parameters could predict early hemorrhagic lesions.

Methods—

Consecutive patients were included in the Lyon rt-PA protocol. Early hematomas (within 24 hours), diagnosed on an anatomoradiological basis (symptomatic and not symptomatic) were considered for the study. Fibrinogen and fibrin(ogen) degradation products (FDP) were assessed at entry and at 2 and 24 hours after the beginning of thrombolysis.

Results—

Of 157 patients, 11 had early parenchymal hematomas (7%), 31 had early hemorrhagic infarcts (19.7%), and 115 had no bleeding (73.2%). In logistic regression, FDP at 2 hours was the single predictor of parenchymal hematomas (OR: 2.5; CI: 1.09 to 5.8), whereas an increase of FDP >200 mg/L multiplied the odds of parenchymal hematoma by 4.95 (IC: 1.09 to 22.4). Early parenchymal hematomas were indicative of a poor prognosis at 3 months (
P
=0.001).

Conclusions—

Early parenchymal hematomas appear as both “malignant” and exclusively related to an explosive increase of FDP at 2 hours, ie, an early fibrinogen degradation coagulopathy (EFDC). All patients scheduled to rt-PA thrombolysis should have an assay of FDP 2 hours after the beginning of thrombolysis: patients with an established EFDC (FDP >200 mg/L) should be monitored specifically, with no antithrombotic drug during the first 72 hours. Patients with FDP >100 mg should share the same monitoring.
Inhibition of angiotensin I–converting enzyme induces radioprotection by preserving murine hematopoietic short-term reconstituting cells
Authors: Charrier Sabine , Michaud Annie , Badaoui Sabrina , Giroux Sébastien , Ezan Eric , Sainteny Françoise , Corvol Pierre , Vainchenker William
Published: April 2004

Angiotensin I–converting enzyme (ACE) inhibitors can affect hematopoiesis by several mechanisms including inhibition of angiotensin II formation and increasing plasma concentrations of AcSDKP (acetyl-N-Ser-Asp-Lys-Pro), an ACE substrate and a negative regulator of hematopoiesis. We tested whether ACE inhibition could decrease the hematopoietic toxicity of lethal or sublethal irradiation protocols. In all cases, short treatment with the ACE inhibitor perindopril protected against irradiation-induced death. ACE inhibition accelerated hematopoietic recovery and led to a significant increase in platelet and red cell counts. Pretreatment with perindopril increased bone marrow cellularity and the number of hematopoietic progenitors (granulocyte macrophage colony-forming unit [CFU-GM], erythroid burst-forming unit [BFU-E], and megakaryocyte colony-forming unit [CFU-MK]) from day 7 to 28 after irradiation. Perindopril also increased the number of hematopoietic stem cells with at least a short-term reconstitutive activity in animals that recovered from irradiation. To determine the mechanism of action involved, we evaluated the effects of increasing AcSDKP plasma concentrations and of an angiotensin II type 1 (AT1) receptor antagonist (telmisartan) on radioprotection. We found that the AT1-receptor antagonism mediated similar radioprotection as the ACE inhibitor. These results suggest that ACE inhibitors and AT1-receptor antagonists could be used to decrease the hematopoietic toxicity of irradiation.
Long-term outcomes in adults with chronic ITP after splenectomy failure
Authors: McMillan Robert , Durette Carol
Published: April 2004

Adult chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder manifested by thrombocytopenia from the effects of antiplatelet autoantibodies and T lymphocyte–mediated platelet cytotoxicity. Multiple studies show that corticosteroid treatment and splenectomy, alone or together, increase platelet counts to safe levels in 60% to 70% of patients. However, there is little information on the outcomes of ITP patients refractory to splenectomy. We studied 114 patients with ITP for whom splenectomy failed and who required additional therapy; long-term follow-up was available on 105 (92%) patients. Seventy-five (71.4%) patients attained stable partial (platelet count greater than 30 × 109/L) or complete (normal platelet count) remission; 51 patients remained in remission after therapy was discontinued, whereas 24 patients required continued treatment. Median time to remission after splenectomy failure was 46 months (range, 1-437 months). Median remission durations were 60 months (range, 10-212 months) for patients off therapy and 48 months (range, 2-167 months) for patients on therapy. Thirty (29.6%) patients remained unresponsive to treatment. Thirty-two patients died, 17 (15.7%) of ITP (bleeding, 11 patients; therapy complications, 6 patients) and 15 (13.9%) of unrelated causes. We conclude that most patients with refractory ITP attain stable remission, though on average this occurs slowly. However, a subpopulation with severe, resistant disease experiences significant morbidity and mortality.
Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI
Authors: Arbab Ali S. , Yocum Gene T. , Kalish Heather , Jordan Elaine K. , Anderson Stasia A. , Khakoo Aarif Y. , Read Elizabeth J. , Frank Joseph A.
Published: April 2004

Recently, there have been several reports using various superparamagnetic iron oxide (SPIO) nanoparticles to label mammalian cells for monitoring their temporal and spatial migration in vivo by magnetic resonance imaging (MRI). The purpose of this study was to evaluate the efficiency and toxicity of labeling cells using 2 commercially available Food and Drug Administration (FDA)-approved agents, ferumoxides, a suspension of dextran-coated SPIO used as an MRI contrast agent, and protamine sulfate, conventionally used to reverse heparin anticoagulation but also used ex vivo as a cationic transfection agent. After labeling of human mesenchymal stem cells (MSCs) and hematopoietic (CD34+) stem cells and other mammalian cells with ferumoxides-protamine sulfate complexes (FE-Pro), cellular toxicity, functional capacity, and quantitative cellular iron incorporation were determined. FE-Pro-labeled cells demonstrated no short- or long-term toxicity, changes in differentiation capacity of the stem cells, or changes in phenotype when compared with unlabeled cells. Efficient labeling with FE-Pro was observed with iron content per cell varying between 2.01 ± 0.1 pg for CD34+ cells and 10.94 ± 1.86 pg for MSCs with 100% of cells labeled. Cell labeling using these agents should facilitate the translation of this method to clinical trials for evaluation of trafficking of infused or transplanted cells by MRI. (Blood. 2004;104:1217-1223)
The homeobox geneXbh1cooperates with proneural genes to specify ganglion cell fate within theXenopusneural retina
Authors: Poggi Lucia , Vottari Teresa , Barsacchi Giuseppina , Wittbrodt Joachim , Vignali Robert
Published: April 2004

Recent studies on vertebrate eye development have focused on the molecular mechanisms of specification of different retinal cell types during development. Only a limited number of genes involved in this process has been identified. In Drosophila, BarH genes are necessary for the correct specification of R1/R6 eye photoreceptors. Vertebrate Bar homologues have been identified and are expressed in vertebrate retinal ganglion cells during differentiation; however, their retinal function has not yet been addressed. In this study, we report on the role of the Xenopus Bar homologue Xbh1 in retinal ganglion cell development and its interaction with the proneural genes Xath5 and Xath3, whose ability to promote ganglion cell fate has been demonstrated. We show that XHB1plays a crucial role in retinal cell determination, acting as a switch towards ganglion cell fate. Detailed expression analysis, animal cap assays and in vivo lipofection assays, indicate that Xbh1 acts as a late transcriptional repressor downstream of the atonal genes Xath3 and Xath5. However, the action of Xbh1 on ganglion cell development is different and more specific than that of the Xath genes, and accounts for only a part of their activities during retinogenesis.
Direct interaction with Hoxd proteins reverses Gli3-repressor function to promote digit formation downstream of Shh
Authors: Chen Yuting , Knezevic Vladimir , Ervin Valerie , Hutson Richard , Ward Yvona , Mackem Susan
Published: April 2004

Sonic hedgehog (Shh) signaling regulates both digit number and identity,but how different distinct digit types (identities) are specified remains unclear. Shh regulates digit formation largely by preventing cleavage of the Gli3 transcription factor to a repressor form that shuts off expression of Shh target genes. The functionally redundant 5′Hoxd genes regulate digit pattern downstream of Shh and Gli3, through as yet unknown targets. Enforced expression of any of several 5′Hoxd genes causes polydactyly of different distinct digit types with posterior transformations in a Gli3(+) background, whereas, in Gli3 null limbs,polydactylous digits are all similar, short and dysmorphic, even though endogenous 5′Hoxd genes are broadly misexpressed. We show that Hoxd12 interacts genetically and physically with Gli3, and can convert the Gli3 repressor into an activator of Shh target genes. Several 5′Hoxd genes,expressed differentially across the limb bud, interact physically with Gli3. We propose that a varying [Gli3]:[total Hoxd] ratio across the limb bud leads to differential activation of Gli3 target genes and contributes to the regulation of digit pattern. The resulting altered balance between `effective'Gli3 activating and repressing functions may also serve to extend the Shh activity gradient spatially or temporally.
EpithelialBmpr1aregulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development
Authors: Andl Thomas , Ahn Kyung , Kairo Alladin , Chu Emily Y. , Wine-Lee Lara , Reddy Seshamma T. , Croft Nirvana J. , Cebra-Thomas Judith A. , Metzger Daniel , Chambon Pierre , Lyons Karen M. , Mishina Yuji , Seykora John T. , Crenshaw E. Bryan , Millar Sarah E.
Published: April 2004

Bone morphogenetic protein (BMP) signaling is thought to perform multiple functions in the regulation of skin appendage morphogenesis and the postnatal growth of hair follicles. However, definitive genetic evidence for these roles has been lacking. Here, we show that Cre-mediated mutation of the gene encoding BMP receptor 1A in the surface epithelium and its derivatives causes arrest of tooth morphogenesis and lack of external hair. The hair shaft and hair follicle inner root sheath (IRS) fail to differentiate, and expression of the known transcriptional regulators of follicular differentiation Msx1,Msx2, Foxn1 and Gata3 is markedly downregulated or absent in mutant follicles. Lef1 expression is maintained, but nuclearβ-catenin is absent from the epithelium of severely affected mutant follicles, indicating that activation of the WNT pathway lies downstream of BMPR1A signaling in postnatal follicles. Mutant hair follicles fail to undergo programmed regression, and instead continue to proliferate, producing follicular cysts and matricomas. These results provide definitive genetic evidence that epithelial Bmpr1a is required for completion of tooth morphogenesis, and regulates terminal differentiation and proliferation in postnatal hair follicles.
Trends in Emergency Department Antibiotic Prescribing for Acute Respiratory Tract Infections
Authors: Thorpe Joshua M , Smith Scott R , Trygstad Troy K
Published: April 2004

BACKGROUND:

Injudicious use of antibiotics is associated with the reported rise in antibiotic-resistant bacteria. With an estimated 26 million antibiotics being prescribed annually in the emergency department (ED), the ED represents an important setting for targeting interventions.

OBJECTIVE:

To provide national estimates of potentially inappropriate antibiotic prescribing during ED visits for acute respiratory tract infections (ARTIs) and examine associations between patient, provider, visit characteristics, and antibiotic prescribing patterns.

METHODS:

A cross-sectional study was conducted of ED visits for ARTIs, identified from pooled 1995–2000 National Hospital Ambulatory Medical Care Survey data. National estimates, descriptive statistics, and multivariate analyses were used to assess antibiotic prescribing patterns.

RESULTS:

An estimated 51.3 million ED visits for ARTIs occurred during the study period, 62% of which had an antibiotic prescribed. For a narrowly defined subset of ARTIs, where antibiotic therapy is nearly always inappropriate (eg, nasopharyngitis, ARTI of multiple or unspecified sites, acute bronchitis), the percentage decreased over the 6-year period from 57% to 44% (p < 0.01). For children ED visits, however, the downward trend occurred almost exclusively in urban EDs. Compared with visits in which a resident or intern physician was involved, the odds of antibiotic prescribing for child ED ARTI visits were 2.2 times higher for staff physicians (95% CI 1.3 to 3.6) and 1.8 times higher for nonphysicians with prescribing privileges (95% CI 1.3 to 2.4).

CONCLUSIONS:

ED antibiotic prescribing for ARTIs has decreased from 1995 to 2000, but still is occurring in well over half of ED visits for ARTI. Further research assessing knowledge and attitudes of patients and providers about antibiotic prescribing is needed.
BUYER BEWARE
Authors: RAPPOPORT J.
Published: April 2004

In this essay I draw attention to a poetics of giving that runs through the body of Letitia Elizabeth Landon's work. Landon (or "L.E.L.") has most frequently interested scholars either as a poet of tragic love or as evidence that early-nineteenth-century women writers could support themselves in a commercial market. But this dual focus remains problematic. Not only have critics generally oversimpliÞed Landon's relationship to love, commodiÞcation, and sales, but also-and more important for my discussion-their Þxation on her role in the capitalist marketplace has made us less ready to analyze her relationship to the gift, her other strategy of exchange. Through her publishing strategies, as well as through the very language of her poetic work, Landon's simultaneous reliance on both gift and sale models complicates the process of exchange. When Landon claims to give instead of sell, her reader's role is undeÞned, and the obligations that the gift entails put Landon in a position of power. In this essay I explore the marketing strategy, thematic approach, formal style, and legacy of reception that comprise Landon's "gift poetics," and I show how this poetics is signiÞcant both for reading her work and for reconsidering a line of women's poetry neglected by Romantic and Victorian scholarship alike. I argue that L.E.L. does not deal in beauty, love, or self, but in power-and that what we see in her art is, Þnally, a deceptively strong poetics of giving mediated by marketing strategy that treated her poetry as "gifts" in order to sell them.
UNNATURAL SELF- SACRIFICE
Authors: BLUMBERG I. M.
Published: April 2004

In this essay I explore Trollope's challenge to traditional Victorian valorizations of sacriÞce. A wide range of Victorian writings, from novels to sermons to economic and sociological treatises, suggests that sacriÞce is virtuous only when it comes without personal reward. In an era of unprecedented personal and national prosperity, Trollope rejected this purist standard for sacriÞce. The Þrst and last novels of his Barsetshire series do away with the attempt to retain a sphere of sacriÞce beyond a capitalistic circuit of exchange where theft and questionably gained surplus consistently threaten ethical life. Instead, the novels allow morally desirable acts to reap reward for their agents, to generate various forms of surplus that can then be fed back into a circuit of sympathetic human relations. In rejecting a sacriÞcial ideal, Trollope poses an everyday communal ethic of beneÞt in place of the idealized, highly individualistic model of self-denial that so many of his contemporaries endorsed.
Interventions to Achieve Tonic Exposure to Levodopa: Delaying or Preventing the Onset of Motor Complications
Authors: Luer Mark S.
Published: April 2004

Variations in levodopa delivery and subsequent dopamine exposure may lead to motor fluctuations and dyskinesias in patients with Parkinson's disease, as the therapeutic window for levodopa narrows with disease progression. Long‐term exposure to the oscillations in levodopa‐derived dopamine also is suggested to cause postsynaptic changes within the dopaminergic system, leading to further reductions in the drug's efficacy. The need to extend the actions of levodopa led to the development of the catechol‐O‐methyltransferase (COMT) inhibitors, which are the newest agents introduced to manage the symptoms of Parkinson's disease. Entacapone and tolcapone are two potent, selective, and reversible COMT inhibitors that effectively augment levodopa's pharmacokinetics by increasing area under the plasma concentration versus time curve and plasma elimination half‐life without significantly affecting peak levodopa concentrations. This enhanced pharmacokinetic effect results in marked improvements in patients' clinical response. In patients experiencing end‐of‐dose wearing‐off, the addition of either entacapone or tolcapone led to improvements in “on” time, “off” time, and the Unified Parkinson's Disease Rating Scale scoring system, even though many patients already were receiving optimum dosages of various other antiparkinsonian drugs. In patients with stable responses to long‐term levodopa, addition of tolcapone significantly reduced the onset of motor fluctuations. These data, combined with the potential for delaying the onset of motor fluctuations, suggest that COMT inhibition may enhance levodopa's short‐ and long‐term efficacy.
Clinical Pharmacy Services, Pharmacist Staffing, and Drug Costs in United States Hospitals
Authors: Bond C. A. , Raehl Cynthia L. , Franke Todd
Published: April 2004

We evaluated direct relationships and associations among clinical pharmacy services, pharmacist staffing, and drug costs in United States hospitals. A database was constructed from the 1992 American Hospital Association's Abridged Guide to the Health Care Field and the 1992 National Clinical Pharmacy Services database. Multiple regression analysis, controlling for severity of illness, was employed to determine the associations. The study population consisted of 934 hospitals. Four clinical pharmacy services were associated with lower drug costs: in‐service education, $77,879.19 ± $56,203.42 (a total of $48,518,735.37 for the 623 hospitals offering this service, p=0.016); drug information, $430,579.84 ± $299,232.76 ($90,852,346.24 for the 211 hospitals offering this service, p=0.015); drug protocol management, $137,333.67 ± $98,617.83 ($45,045,443.76 for the 328 hospitals offering this service, p=0.049); and admission drug histories, $213,388.21 ± $201,537.85 ($5,548,093.46 for the 26 hospitals offering this service, p=0.011). As staffing increased for hospital pharmacy administrators (p<0.0001), dispensing pharmacists (p<0.0001), and pharmacy technicians (p<0.0001), drug costs increased. As staffing increased for clinical pharmacists, drug costs decreased (p=0.018). The results of this study show that increased staff levels of clinical pharmacists and some clinical pharmacy services are associated with reduced hospital drug costs.
Amiodarone‐Induced Pulmonary Toxicity
Authors: Kanji Zahra , Sunderji Rubina , Gin Kenneth
Published: April 2004

Amiodarone‐induced pulmonary toxicity (AIPT) is one of the most serious adverse effects of amiodarone therapy and can be fatal. Therefore, vigilant monitoring is advised. Baseline chest radiograph and pulmonary function tests and follow‐up chest films at 3‐month intervals are advocated. However, since abnormalities on these two examinations do not always precede symptoms, patient self‐reports of respiratory symptoms appear to be the best method for early detection of AIPT.
Upper Gastrointestinal Tract Bleeding in Critically Ill Pediatric Patients
Authors: Crill Catherine M. , Hak Emily B.
Published: April 2004

Similar to adults, children under physiologic stress can develop an imbalance in defensive (mucosal layer, motility) and aggressive (gastric acid, bile salts, enzymes) factors responsible for maintaining a healthy gastrointestinal tract. Hypoxia in the gastrointestinal tract likely disrupts the defensive factors, thereby permitting damage by aggressive factors to upper gastrointestinal epithelium that may progress to stress ulceration and acute upper gastrointestinal tract bleeding (UGIB). The basic pathophysiology may be similar in children and adults; however, differences in the time to developing ulceration, ulcer location, and number of ulcers have been reported. Functional development of the gastrointestinal tract is influenced by disease, gestational and postnatal age, and exposure to and type of enteral feedings, thereby confounding the development and prophylaxis of UGIB in neonates and infants. In addition, pharmacotherapy decisions are often complicated by drug administration issues and adverse effects.
Does the Addition of Pindolol Accelerate or Enhance the Response to Selective Serotonin Reuptake Inhibitor Antidepressants?
Authors: Puzantian Talia , Kawase Kristina
Published: April 2004

Although in the last few years new antidepressants have become available in the United States, responses in many patients differ, from none, to partial, to delayed therapeutic response to the agents. If the antidepressant properties of these drugs could be enhanced or accelerated, it might be possible to improve patient functioning and quality of life. Pindolol, a serotonin 1A autoreceptor antagonist, accelerates and augments the therapeutic effects of antidepressants, especially selective serotonin reuptake inhibitors.
Use of Transdermal Amitriptyline Gel in a Patient with Chronic Pain and Depression
Authors: Scott Mollie A. , Letrent Kristen J. , Hager Kellie L. , Burch Jennifer L.
Published: April 2004

A man with severe inflammatory bowel disease suffered from chronic abdominal pain and depression. A transdermal amitriptyline gel preparation was compounded since he was unable to take drugs orally. Serum concentrations of amitriptyline and its active metabolite nortriptyline were measured over 24 hours. Symptoms of depression were monitored before starting transdermal therapy and at the end of 6 weeks. Pain symptoms and amitriptyline adverse drug events were monitored daily. Steady‐state serum concentrations of drug and metabolite were within the therapeutic range over 24 hours. The patient reported that his mood was improved but his abdominal pain remained unchanged. Transdermal amitriptyline gel was well tolerated and is an alternative delivery system in patients unable to take drugs orally.
Intravenous Azithromycin‐Induced Ototoxicity
Authors: Bizjak Eric D. , Haug Marcus T. , Schilz Robert J. , Sarodia Bipin D. , Dresing Janna M.
Published: April 2004

Intravenous azithromycin is increasingly administered for treatment of hospitalized patients with community‐acquired pneumonia. Macrolide antibiotics cause ototoxicity, which occurs most frequently when high serum concentrations are achieved. Current dosing guidelines for intravenous azithromycin can result in much higher serum concentrations than is seen with oral administration. We describe a 47‐year‐old woman who developed complete deafness after receiving 8 days of intravenous azithromycin.
Impact of Rifampin on Serum Amiodarone Concentrations in a Patient with Congenital Heart Disease
Authors: Zarembski Dawn G. , Fischer Staci A. , Santucci Peter A. , Porter Mary T. , Costanzo Maria Rosa , Trohman Richard G.
Published: April 2004

A 33‐year‐old woman with congenital heart disease and atrial and ventricular arrhythmias, managed over the long term with an implantable cardioverter defibrillator, epicardial pacing system, and amiodarone, experienced an increase in palpitations and a shock from her defibrillator. Evaluation revealed decreases in amiodarone and desethylamiodarone serum concentrations from previous levels. Rifampin had been added to her therapy 5 weeks earlier. Increases in amiodarone and desethylamiodarone concentrations were observed after an increase in the amiodarone dosage and discontinuation of rifampin. The time course suggested that the addition of rifampin led to reductions in serum concentrations of both the drug and metabolite.
Tolterodine, a New Antimuscarinic Drug for Treatment of Bladder Overactivity
Authors: Guay David R. P.
Published: April 2004

Tolterodine is a nonsubtype selective antimuscarinic agent recently approved as therapy in patients with overactive bladder with symptoms of urinary frequency, urgency, or urge incontinence. It acts by muscarinic receptor blockade in the bladder wall and detrusor muscle. Despite short terminal disposition half‐lives of 2–3 and 3–4 hours for tolterodine and its active 5‐hydroxy metabolite, respectively, twice/day dosing is effective due to the drug's prolonged pharmacodynamic effects. Dosage adjustment is recommended in the presence of hepatic impairment and during concurrent therapy with drugs that inhibit cytochrome P450 2D6 and 3A4 isozymes. Tolterodine significantly reduces clinically relevant end points such as number of micturitions and number of incontinence episodes/day. In general, it is superior to placebo and equivalent to oxybutynin in this regard. As might be expected from its pharmacologic profile, the principal adverse effects of the drug are anticholinergic. In clinical trials, tolterodine was tolerated significantly better than oxybutynin. Its relative merits as a first‐ or second‐line agent for patients intolerant of oxybutynin are unclear. Until pharmacoeconomic analyses are conducted that clearly justify use of this more expensive agent, tolterodine is perhaps best reserved for patients who are intolerant of or fail oxybutynin therapy.
Comparison of Two Home Blood Pressure Monitors with a Mercury Sphygmomanometer in an Ambulatory Population
Authors: Johnson Kjel A. , Partsch Deborah J. , Gleason Patrick , Makay Kelly
Published: April 2004

We performed a randomized, single‐visit, crossover study to compare the precision of a digital monitor and an aneroid monitor relative to a desktop mercury sphygmomanometer (DMS). Three blood pressure measurements per patient, one per device, were taken over 25 minutes. Of 99 patients, 95 had complete blood pressure data. Systolic blood pressures measured with the digital monitor were significantly different from those with the DMS (p<0.01). Thirty‐four percent of systolic and 48% of diastolic pressures measured with the digital monitor were within ± 5 mm Hg of the DMS. The aneroid monitor performed significantly better than the digital monitor, with 54% of systolic (p<0.01) and 58% of diastolic blood pressures within ± 5 mm Hg of the DMS standard. Health care providers are encouraged to supervise patients' initial use of a home blood pressure monitor and calibrate readings against a standard mercury sphygmomanometer.
(R)‐2‐Diphenylphosphino‐2′‐Methoxy‐1,1′‐Binaphthyl
Authors: Uozumi Yasuhiro , Kawatsura Motoi , Hayashi Tamio
Published: April 2004

(R)‐2‐Diphenylphosphino‐2′‐methoxy‐1, 1′‐binaphthyl

R (
R
)‐(+)‐1, 1′‐bi‐2‐maphthol 1

I (
R
)‐2, 2′‐Bis (trifluoromethanesulfonyloxy)‐1, 1′‐binaphthyl 2

(R)‐(+)‐2‐Diphenyl phosphinyl‐2′‐trifluoromethanesulfonyloxy‐1, 1′‐binaphthyl 3

(R)‐(−)‐2‐Diphenyl phosphinyl‐2′‐hydroxy‐1, +′‐binaphthyl 4

(R)‐(+)‐2‐Diphenyl phosphinyl‐2′‐methoxy‐1, 1′‐binaphthyl 5

P (R)‐(+)‐2‐Diphenyl phosphino‐2′‐methoxy‐1, 1′‐binaphithyl 6
Preparation and Use of N,N′‐Di‐Boc‐N″‐Triflylguanidine
Authors: Baker Tracy J. , Tomioka Mika , Goodman Murray
Published: April 2004

N, N′‐Di‐boc‐N″‐triflyguanidine

R N, N′‐Di‐boc‐guanidine

I N,N′‐Di‐boc‐N″‐triflyguanidine

R Benzylamine

P N, N′‐Bis (tert‐butoxycarbonyl‐N″‐benzylguanidine
Synthesis of Penta‐1,2‐dien‐4‐one (Acetylallene)
Authors: Constantieux Thierry , Buono Gérard
Published: April 2004

Penta‐1,2‐dien‐4‐one (or Acetylallene)

R Acetylacetone (or 2,4‐pentanedione

P Penta‐1,2‐dien‐4‐one (or Acetylallene)
Bicyclopropylidene
Authors: de Meijere Armin , Kozhushkov Sergei I. , Späth Thomas
Published: April 2004

Bicyclopropylidine

R Methyl cyclopropanecarboxylate

I 1‐Cyclopropylcyclopropanol

1‐Bromo‐1‐cyclopropylcyclopropane

P Bicyclopropylidine
Preparation of (E)‐1‐Dimethylamino‐3‐tert‐Butyldimethylsiloxy‐1,3‐Butadiene
Authors: Kozmin Sergey A. , He Shuwen , Rawal Viresh H.
Published: April 2004

(E)‐1‐Dimethylamino‐3‐tert‐butyldimethylsiloxy‐1,3‐butadiene

R Acetylacetaldehyde dimethyl acetal

I (E)‐4‐Dimethylamino‐3‐buten‐2‐one 1

P (E)‐1‐Dimethyl‐3‐tert‐butyldimethylsiloxy‐1,3‐butadiene 2
Diethyl [(Phenylsulfonyl)Methyl]Phosphonate
Authors: Enders D. , von Berg S. , Jandeleit B.
Published: April 2004

Diethyl [(phenylsulfonyl)methyl]phosphonate

R Thiophenol

I Chloromethyl phenyl sulfide

Diethyl [(phenylthio)methyl]phosphonate

P Diethyl [(phenylsulfonyl)methyl]phosphonate 1
[4 + 3] Cycloaddition of Aminoallyl Cations with 1,3‐Dienes:11‐Oxatricyclo[4.3.1.12,5]Undec‐3‐en‐10‐one
Authors: Oh Jonghoon , Ziani‐Cherif Chewki , Choi Jong‐Ryoo , Jin Kun Cha
Published: April 2004

11‐Oxatricyclo[4.3.1.1{2,5}]undec‐3‐en‐10‐one

R 2‐chlorocyclohexanone

I 6‐chloro‐1‐pyrrolidinocyclohexene 1

P 11‐Oxatricyclo[4.3.1.1{2,5}]undec‐3‐en‐10‐one