bluuebunny/crossref_metadata_2025 huggingface dataset:
Perioperative Nesiritide Versus Milrinone in High-Risk Coronary Artery Bypass Graft Patients
Authors: Brackbill Marcia L , Stam M Denton , Schuller-Williams Rebecca V , Dhavle Ajit A
Published: February 2007

Background:

Patients with left-ventricular dysfunction have an increased risk of developing heart failure after coronary artery bypass graft (CABG) surgery. Therapies to maintain cardiac output in such patients warrant investigation. Nesiritide is unique among intravenous medications used to manage heart failure. It mediates natriuresis and vasodilation and suppresses the renin–angiotensin'aldosterone axis. Nesiritide may attenuate the body's neurohormonal response to myocardial stretch after CABG and provide clinical benefit in the immediate postoperative period.

Objective:

To determine whether perioperative infusion of nesiritide improves clinical outcomes compared with milrinone therapy.

Methods:

A prospective, open-label, randomized controlled trial was conducted in 40 consecutive hemodynamically stable patients with ejection fractions 35% or less undergoing CABG surgery. Patients were randomized to receive either an intraoperative bolus of nesiritide or milrinone followed by a 24 hour infusion of each agent. Length of postoperative intensive care unit stay was the primary outcome variable evaluated. Incidence of postoperative heart failure, 30 day readmission rates, mortality, and other clinical parameters were also compared.

Results:

Patients receiving nesiritide had a mean ± SD postoperative intensive care unit stay of 50.6 ± 46.8 hours compared with 44.1 ± 23.5 hours in those receiving milrinone (p = 0.578). Incidence of postoperative heart failure was also not significantly different between the drugs (p = 0.259). Thirty day follow-up confirmed no difference in hospital readmission rates between nesiritide and milrinone (p = 0.661). No differences in mortality were observed during hospitalization or 30 days of follow-up.

Conclusions:

Nesiritide does not decrease postoperative intensive care unit stay or other clinical parameters compared with milrinone in high-risk patients with hemodynamically stable left-ventricular function undergoing CABG surgery.
Alteration in Renal Organic Anion Transporter 1 After Ischemia/Reperfusion in Cadaveric Renal Allografts
Authors: Kwon Osun , Hong Seok-Min , Blouch Kristina
Published: February 2007

We have previously shown that postischemic injury to renal allografts results in profound impairment of p-aminohippuric acid (PAH) extraction. To elucidate the cellular integrity of the human organic anion transporter 1 (hOAT1) in postischemic acute renal failure (ARF), immunohistochemical analysis of hOAT1 was performed in cadaveric renal allografts using confocal microscopy for three-dimensional reconstruction of serial optical images. Biopsy samples were obtained from 10 cadaveric renal allografts 1 hr after reperfusion during transplant operation. Control tissues were obtained from four living donors of healthy kidneys immediately before an arterial clamp was applied to the renal artery. Control tissues demonstrated hOAT1 distributed to basolateral membrane of proximal tubule cells. In contrast, maldistribution of hOAT1 to cytoplasm and/or diminution of the protein was noted in cadaveric allografts. Characteristics of maldistribution were variable: disappearance of lateral distribution, diffuse cytoplasmic aggregates, apical cytoplasmic aggregates, and disappearance of the staining. In addition, iothalamate and PAH clearances were performed on posttransplant days 3–7 in 18 recipients of a cadaveric renal allograft. PAH clearance was depressed <250 ml/min in all but three subjects. We conclude that reperfused, transplanted kidneys exhibit maldistribution of hOAT1 in proximal tubule cells, resulting in impairment of PAH clearance. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.
Possible Function of Caudal Nuclear Pocket
Authors: Haraguchi Celina M. , Mabuchi Tadashi , Hirata Shuji , Shoda Tomoko , Tokumoto Toshinobu , Hoshi Kazuhiko , Yokota Sadaki
Published: February 2007

Many temporarily functioning proteins are generated during the replacement of nucleoproteins in the nuclei of late spermatids and seem to be degraded in the nucleus. This study was designed to clarify the involvement of the ubiquitin-proteasome degradation system in the nucleus of rat developing spermatids. Thus, we studied the nuclear distribution of polyubiquitinated proteins (pUP) and proteasome in spermiogenic cells and sperm using postembedding immunoelectron microscopy. We divided the nuclear area of late spermatids into two regions: (1) a dense area composed of condensed chromatin and (2) a nuclear pocket in the neck region. The latter was located in the caudal nuclear region and was surrounded by redundant nuclear envelope. We demonstrated the presence of pUP in the dense area and nuclear pocket, proteasome in the nuclear pocket, and clear spots in the dense area of rat spermatids. Using quantitative analysis of immunogold labeling, we found that fluctuation of pUP and proteasome levels in late spermatogenesis was mostly synchronized with disappearance of histones and transitional proteins reported previously. In the nuclei of human sperm, pUP was detected in the dense area, whereas proteasome was in the nuclear vacuoles and clear spots. These results strongly suggest that pUP occur in the dense nuclear area of developing spermatids and that the ubiquitin-proteasome system is more actively operational in the nuclear pocket than dense area. Thus, the nuclear pocket might be the degradation site for temporarily functioning proteins generating during condensation of chromatin in late spermatids.
Distinct alleles of mannose-binding lectin (MBL) and surfactant proteins A (SP-A) in patients with chronic cavitary pulmonary aspergillosis and allergic bronchopulmonary aspergillosis
Authors: Vaid Mudit , Kaur Savneet , Sambatakou Helen , Madan Taruna , Denning David W. , Sarma P. Usha
Published: February 2007

Clin Chem Lab Med 2007;45:183–6.
HER-2 protein concentrations in breast cancer cells increase before immunohistochemical and fluorescence in situ hybridization analysis turn positive
Authors: Olsen Dorte A. , Østergaard Birthe , Bokmand Susanne , Wamberg Peter A. , Jakobsen Erik H. , Brandslund Ivan
Published: February 2007

Clin Chem Lab Med 2007;45:177–82.
Accreditation of medical laboratories in the European Union
Authors: Huisman Wim , Horvath A. Rita , Burnett David , Blaton Victor , Czikkely Rózsa , Jansen Rob T.P. , Kallner Anders , Kenny Desmond , Mesko Pika , Plebani Mario , Queralto José , Schumann Gerhard , Šprongl Luděk , Vitkus Dalius , Wallinder Hans , Zerah Simone
Published: February 2007

: Using a questionnaire, the EC4 (European Communities Confederation of Clinical Chemistry and Laboratory Medicine) has collated an inventory of the accreditation procedures for medical laboratories in the EU.

: Accreditation of medical laboratories in the countries of the EU is mostly carried out in cooperation with national accreditation bodies. These national accreditation bodies work together in a regional cooperation, the European Cooperation for Accreditation (EA). Professionals are trained to become assessors and play a prominent role in the accreditation process. The extent of the training is diverse, but assessors are kept informed and up-to-date by annual meetings. The frequency of assessments and surveillance visits differs from country to country and ranges from 1 to 4 years. More harmonisation is needed in this respect, based on a frequency that can be pragmatically handled by laboratory professionals. In the majority of EA bodies, accreditation is carried out on a test-by-test basis. Many professionals would prefer accreditation of the entire service provided within the actual field of testing (i.e., haematology, immunology, etc.), with accreditation granted if the majority of tests offered within a service field fulfil the requirements of the ISO 15189 standard. The scope of accreditation is a major point of discussions between the EC4 Working Group on Accreditation and representatives of accreditation bodies in the EA Medical Laboratory Committee.

Clin Chem Lab Med 2007;45:268–75.
Patient hydration: a major source of laboratory uncertainty
Authors: Ritchie Robert F. , Ledue Thomas B. , Craig Wendy Y.
Published: February 2007

Movement of body water from compartment to compartment during any time period is attributable to forces active within and upon each space. The result of these forces leads to transfer of water between intravascular and extravascular compartments, as well as shifts between extracellular and intracellular spaces. The importance of these shifts and of the associated mechanism was described by Ernest Starling in 1896 in very much the same manner as it is viewed today. The end result of fluid transfer and its physiological and laboratory consequences has not been fully appreciated. Despite awareness that fluid shifts can affect laboratory analytical results, little recent investigation has addressed the problem in the routine clinical laboratory. Thus, the potential for significant misinterpretation remains. For example, it is known that individual laboratory test values can vary widely, depending on many factors including the subject's posture during and immediately before phlebotomy, leading to significant changes in the interpretation of blood analyte values. Furthermore, a variety of ubiquitous environmental effects have additional impact on fluid distribution and thus on test values. In other words, patient hydration status is a major pre-analytical variable that needs to be addressed by the clinical laboratory.

The need to adjust data for patient hydration status is especially important in the case of colloid analytes for which the dynamic range includes a narrow “gray zone” where hydration changes of a few percentage points can change the clinical implications. The crucial importance of this adjustment is underscored by the fact that neither the testing laboratory nor the clinician are aware of this unseen circumstance and are thus compelled to work with data that do not necessarily reflect the clinical situation.

Clin Chem Lab Med 2007;45:158–66.
Hyperhomocysteinemia and cardiovascular risk in postmenopausal women: the role of folate supplementation
Authors: Villa Paola , Suriano Rosanna , Costantini Barbara , Macrì Francesca , Ricciardi Luigi , Campagna Giuseppe , Lanzone Antonio
Published: February 2007

In the postmenopausal period, cardiovascular diseases are a frequent chronic condition leading to high risk of myocardial infarction and death. Recently hyperhomocysteinemia and even mildly elevated plasma concentrations of homocysteine have been recognized as independent risk factors for vascular damage predisposing to arteriosclerosis. Elevated plasma levels of homocysteine induce vascular endothelial damage and are frequently associated with low folate levels.

In this review we evaluate literature data on some aspects related to menopause and homocysteine metabolism. In particular, we show the effect of folic acid supplementation on homocysteine concentrations and on homocysteine-related thiols, such as cysteine and cysteine-glycine, as well as the relationship with glucose, insulin, and lipidic metabolism in postmenopausal women. We also analyze the influence of folate supplementation on endothelial function, by brachial artery flow-mediated dilatation (endothelium-dependent) and nitroglycerine-induced dilatation (endothelium-independent) before and after a methionine load.

Folate administration in postmenopausal women is able to reduce high plasma homocysteine levels and to modify impaired endothelial function induced by hyperhomocysteinemia.

Clin Chem Lab Med 2007;45:130–5.
Multisensory Integration in the Ventral Intraparietal Area of the Macaque Monkey
Authors: Avillac Marie , Ben Hamed Suliann , Duhamel Jean-René
Published: February 2007

The goal of this study was to characterize multisensory interaction patterns in cortical ventral intraparietal area (VIP). We recorded single-unit activity in two alert monkeys during the presentation of visual (drifting gratings) and tactile (low-pressure air puffs) stimuli. One stimulus was always positioned inside the receptive field of the neuron. The other stimulus was defined so as to manipulate the spatial and temporal disparity between the two stimuli. More than 70% of VIP cells showed a significant modulation of their response by bimodal stimulations. These cells included both bimodal cells, i.e., cells responsive to both tested modalities, and seemingly unimodal cells, i.e., cells responding to only one of the two tested modalities. This latter observation suggests that postsynaptic latent mechanisms are involved in multisensory integration. In both cell categories, neuronal responses are either enhanced or depressed and reflect nonlinear sub-, super-, or additive mechanisms. The occurrence of these observations is maximum when stimuli are in temporal synchrony and spatially congruent. Interestingly, introducing spatial or temporal disparities between stimuli does not affect the sign or the magnitude of interactions but rather their occurrence. Multisensory stimulation also affects the neuronal response latencies of bimodal stimuli. For a given neuron, these are on average intermediate between the two unimodal response latencies, again suggesting latent postsynaptic mechanisms. In summary, we show that the majority of VIP neurons perform multisensory integration, following general rules (e.g., spatial congruency and temporal synchrony) that are closely similar to those described in other cortical and subcortical regions.
Neuroprotective Effects of Regulators of the Glycogen Synthase Kinase-3β Signaling Pathway in a Transgenic Model of Alzheimer's Disease Are Associated with Reduced Amyloid Precursor Protein Phosphorylation
Authors: Rockenstein Edward , Torrance Magdalena , Adame Anthony , Mante Michael , Bar-on Pazit , Rose John B. , Crews Leslie , Masliah Eliezer
Published: February 2007

The glycogen synthase kinase-3β (GSK3β) pathway plays an important role in mediating neuronal fate and synaptic plasticity. In Alzheimer's disease (AD), abnormal activation of this pathway might play an important role in neurodegeneration, and compounds such as lithium that modulate GSK3β activity have been shown to reduce amyloid production and tau phosphorylation in amyloid precursor protein (APP) transgenic (tg) mice. However, it is unclear whether regulation of GSK3β is neuroprotective in APP tg mice. In this context, the main objective of the present study was to determine whether pharmacological or genetic manipulations that block the GSK3β pathway might ameliorate the neurodegenerative alterations in APP tg mice and to better understand the mechanisms involved. For this purpose, two sets of experiments were performed. First, tg mice expressing mutant human APP under the Thy1 promoter (hAPP tg) were treated with either lithium chloride or saline alone. Second, hAPP tg mice were crossed with GSK3β tg mice, in which overexpression of this signaling molecule results in a dominant-negative (DN) effect with inhibition of activity. hAPP tg mice that were treated with lithium or that were crossed with DN–GSK3β tg mice displayed improved performance in the water maze, preservation of the dendritic structure in the frontal cortex and hippocampus, and decreased tau phosphorylation. Moreover, reduced activation of GSK3β was associated with decreased levels of APP phosphorylation that resulted in decreased amyloid-β production. In conclusion, the present study showed that modulation of the GSK3β signaling pathway might also have neuroprotective effects in tg mice by regulating APP maturation and processing and further supports the notion that GSK3β might be a suitable target for the treatment of AD.
Integration of Lobula Plate Output Signals by DNOVS1, an Identified Premotor Descending Neuron
Authors: Haag Juergen , Wertz Adrian , Borst Alexander
Published: February 2007

Many motion-sensitive tangential cells of the lobula plate in blowflies are well described with respect to their visual response properties and the connectivity among them. They have large and complex receptive fields with different preferred directions in different parts of their receptive fields matching the optic flow that occurs during various flight maneuvers. However, much less is known about how tangential cells connect to postsynaptic neurons descending to the motor circuits in the thoracic ganglion and how optic flow is represented in these downstream neurons. Here we describe the physiology and the connectivity of a prominent descending neuron called DNOVS1 (for descending neurons of the ocellar and vertical system). We find that DNOVS1 is electrically coupled to a subset of vertical system cells. The specific wiring leads to a preference of DNOVS1 for rotational flow fields around a particular body axis. In addition, DNOVS1 receives input from interneurons connected to the ocelli.
Dopamine Gates Action Potential Backpropagation in Midbrain Dopaminergic Neurons
Authors: Gentet Luc J. , Williams Stephen R.
Published: February 2007

Dopamine is released from both axonal and somatodendritic sites of midbrain dopaminergic neurons in an action potential-dependent manner. In contrast to the majority of central neurons, the axon of dopaminergic neurons typically originates from a dendritic site, suggesting a specialized computational function. Here, we examine the initiation and spread of action potentials in dopaminergic neurons of the substantia nigra pars reticulata and reveal that the displacement of the axon to a dendritic site allows highly compartmentalized electrical signaling. In response to a train of synaptic input, action potentials initiated at axon-bearing dendritic sites formed a variable trigger for invasion to the soma and contralateral dendritic tree, with action potentials often confined to the axon-bearing dendrite. The application of dopamine increased this form of electrical compartmentalization, an effect mediated by a tonic membrane potential hyperpolarization leading to an increased availability of a class of voltage-dependent potassium channel. These data suggest that the release of dopamine from axonal and somatodendritic sites are dissociable, and that dopamine levels within the midbrain are dynamically controlled by the somatodendritic spread of action potentials.
Dominant Role of βγ Subunits of G-Proteins in Oxytocin-Evoked Burst Firing
Authors: Wang Yu-Feng , Hatton Glenn I.
Published: February 2007

Pulsatile neuropeptide secretion is associated with burst firing patterns; however, intracellular signaling cascades leading to bursts remain unclear. We explored mechanisms underlying burst firing in oxytocin (OT) neurons in the supraoptic nucleus in brain slices from lactating rats. Application of 10 pmOT for 30 min or progressively rising OT concentrations from 1 to 100 pminduced burst firing in OT neurons in patch-clamp recordings. Burst generation was blocked by OT antagonist and ionotropic glutamate receptor blockers or tetanus toxin. Blocking G-protein activation with suramin or intracellular GDP-β-S, but not intracellularly administered antibody against the OT-receptor (OTR) C terminus, blocked bursts. Moreover, pretreatment of slices with pertussis toxin, an inhibitor of Gi/o-proteins, did not block OT-evoked bursts, suggesting that Gi/Goactivation is unnecessary for burst generation. Thus, we further examined Gαq/11-associated signaling pathways in OT-evoked bursts. Inhibition of phospholipase C or RhoA/Rho kinase did not block bursts. Activation of Gβγ subunits using myristoylated Gβγ-binding peptide (mSIRK) caused bursts, whereas intracellularly loaded antibody against Gβ subunit blocked OT-evoked bursts. Blocking Src family kinase, but not phosphatidylinositol 3-kinase, occluded OT-evoked bursts. Similar to the effects of OT on EPSCs, mSIRK inhibited tonic EPSCs and elicited EPSC clustering. Finally, suckling caused dissociation of OTRs and Gβ subunits from Gαq/11subunits shown by coimmunoprecipitation and immunocytochemistry, supporting crucial roles for OTRs and Gβγ subunits in the milk-ejection reflex. We conclude that Gβγ subunits play a dominant role in burst firing evoked by applied OT or by suckling.
Upregulation of Substance P in Low-Threshold Myelinated Afferents Is Not Required for Tactile Allodynia in the Chronic Constriction Injury and Spinal Nerve Ligation Models
Authors: Hughes David I. , Scott Dugald T. , Riddell John S. , Todd Andrew J.
Published: February 2007

It has been proposed that substance P and calcitonin gene-related peptide (CGRP) are upregulated in low-threshold myelinated primary afferents after certain types of nerve injury, and that release of substance P from these afferents contributes to the resulting tactile allodynia. To test this hypothesis, we looked for neuropeptides in Aβ primary afferent terminals in the ipsilateral gracile nucleus and spinal dorsal horn in three nerve injury models: sciatic nerve transection (SNT), spinal nerve ligation (SNL), and chronic constriction injury (CCI). We also looked for evidence of neurokinin 1 (NK1) receptor internalization in the dorsal horn after electrical stimulation of Aβ afferents. We found no evidence of either substance P or CGRP expression in injured Aβ terminals in the spinal cord in any of the models. Although substance P was not detected in terminals of injured afferents in the gracile nucleus, CGRP was expressed in between 32 and 68% of these terminals, with a significantly higher proportion in the SNL and CCI models, compared with SNT. In addition, we did not detect any Aβ-evoked NK1 receptor internalization in neurons from laminas I, III, or IV of the dorsal horn in the CCI or SNL models. These results do not support the proposal that substance P is present at significant levels in the terminals of injured Aβ primary afferents in neuropathic models. They also suggest that any release of substance P from injured Aβ afferents is unlikely to activate NK1 receptors in the dorsal horn or contribute to neuropathic pain.
Dopaminergic Regulation of Inhibitory and Excitatory Transmission in the Basolateral Amygdala–Prefrontal Cortical Pathway
Authors: Floresco Stan B. , Tse Maric T.
Published: February 2007

Projections from the basolateral amygdala (BLA) and dopamine (DA) input from the ventral tegmental area (VTA) converge in the medial prefrontal cortex (mPFC), forming a neural circuit implicated in certain cognitive and emotional processes. However, the role that DA plays in modulating activity in the BLA–mPFC pathway is unknown. The present study investigated the mechanisms by which DA modulates BLA-evoked changes in mPFC neural activity, using extracellular single-unit recordings in urethane-anesthetized rats. BLA stimulation evoked two distinct types of responses in separate populations of mPFC neurons: monosynaptic, excitatory responses and, more commonly, inhibition of spontaneous firing. Stimulation of the VTA or local iontophoretic application of DA attenuated BLA-evoked inhibition of PFC neuron firing. Administration of selective DA receptor agonists revealed that these effects were mediated by D2and D4(but not D1) receptors. In addition, VTA stimulation or DA application attenuated BLA-evoked firing of a separate population of mPFC neurons in a frequency-dependent manner; firing evoked by higher-frequency stimulation of the BLA was less inhibited than that evoked by single-pulse stimulation. Attenuation of BLA-evoked firing was also induced by of D1(but not D2or D4) receptor agonists. These data indicate that dissociable DA receptor mechanisms regulate the balance of excitatory and inhibitory transmission in BLA–mPFC circuits, biasing toward an increase in the excitatory influence that the BLA exerts over populations of mPFC neurons. These findings may have important implications for understanding the pathophysiology underlying emotional and cognitive disturbances present in disorders such as depression and drug addiction.
Palestinian Youth and Political Activism: The Emerging Internet Culture and New Modes of Resistance
Authors: Khoury-Machool Makram
Published: February 2007

The information technology revolution and the introduction of the Internet in the last decade have transformed the life of individuals and groups across the globe. One unique example of the remarkable impact of this new medium on the life of a marginalised society is the impact of the Internet on the life of Palestinians. The author demonstrates that, since the outbreak of the second Palestinian Intifada on 28 September 2000, and the drop of the average income of Palestinian households living in the 1967 Palestinian territories, a sharp increase in the number of Palestinian Internet users, especially youths, has been reported through connectivity in schools, universities and cafes. In universities, a method of instruction has been developed to maintain higher education, since students frequently cannot reach the campus due to conditions of siege. The author also argues that, due to the pertinent socio-political conditions of Palestinian youths and students under occupation, the Internet now acts as a medium between teachers and students, as well as a tool for intense politicisation and cyber-resistance. With constant Internet access possible for over 25% of the Palestinian population, a new youth culture has emerged amongst Palestinians, in particular at schools and universities. By organising relations between teachers, students and the youth in general, as well as with various sectors of the Palestinian population, the Internet now acts as a broad and collective front for national peaceful political resistance, and is one of the most central elements of everyday life. It is to be noted that this phenomenon should be seen in the specific socio-political, economic and cultural context of the Palestinians, unconnected to the introduction of the Internet in the broader Arab world. It should also be noted that, as a result, Palestinians are now the largest group of users of the Internet in the Arab world.
Gambling with the Future of Public Education: Risk, Discipline, and the Moralizing of Educational Politics in Corporate Media
Authors: Saltman Kenneth
Published: February 2007

This article discusses how representations of individual discipline and risk-taking in mass media inform the broader public discourses about public education and the public sector generally. Such representations and narratives about individual discipline and risk-taking often function in mass media as moral imperatives of consumer culture. Such moral imperatives of consumer culture not only replace a civic morality of political engagement more consistent with democratic ideals and participatory culture but also typify and even stimulate the shifting of politics onto a moral register and language that has characterized neo-liberal ideology, third way post-politics, and that informs contemporary US politics, especially evident during the ‘War on Terror.’ The article discusses these matters through the media spectacle of a Utah woman who permanently tattooed an advertisement for a casino on her face to pay for her son's private school tuition and through the gambling problem of former Secretary of Education and educational entrepreneur William Bennett.
Deficits in Surface Force Production During Seated Reaching in People After Stroke
Authors: Reisman Darcy S , Scholz John P
Published: February 2007

Background and Purpose

In order to design effective treatment strategies for the rehabilitation of reaching after stroke, it is necessary to understand the underlying deficits. Although the kinematic aspects of reaching after stroke have been studied frequently, little attention has been paid to the surface force production underlying this behavior. The purpose of this study was to investigate surface force production and its coordination with arm movement during seated reaching in a group of people with hemiparesis.

Subjects

Seven people with mild right hemiparesis after stroke and 7 people who were neurologically healthy participated.

Methods

Subjects performed seated reaching at 160% their normal speed toward ipsilateral and contralateral targets placed 160% beyond arm reach. Surface forces beneath the seat and feet and 3-dimensional hand movement and joint motions of the upper extremity and trunk were recorded.

Results

A weight shift from seat to feet occurred earlier whereas the onset of medial-lateral seat force was delayed and smaller in magnitude in people with hemiparesis.

Discussion and Conclusion

The results suggest that the normal magnitude and timing of surface force production during reaching beyond arm’s length are altered in people with even mild hemiparesis after stroke, particularly during reaching toward the hemiparetic side.
Hop Testing Provides a Reliable and Valid Outcome Measure During Rehabilitation After Anterior Cruciate Ligament Reconstruction
Authors: Reid Andrea , Birmingham Trevor B , Stratford Paul W , Alcock Greg K , Giffin J Robert
Published: February 2007

Background and Purpose

Although various hop tests have been proposed as performance-based outcome measures following anterior cruciate ligament (ACL) reconstruction, limited reports of their measurement properties exist. The purpose of this study was to investigate the reliability and longitudinal validity of data obtained from hop tests during rehabilitation after ACL reconstruction.

Subjects

Forty-two patients, 15 to 45 years of age, who had undergone ACL reconstruction participated in the study.

Methods and Measures

The study design was prospective and observational with repeated measures. The subjects performed a series of 4 hop tests on 3 separate occasions within the 16th week following surgery and on a fourth occasion 6 weeks later. The tests were a single hop for distance, a 6-m timed hop, a triple hop for distance, and crossover hops for distance. Performance on the ACL-reconstructed limb was expressed as a percentage of the performance on the nonoperative limb, termed the “limb symmetry index.” Subjects also completed the Lower Extremity Functional Scale and a global rating of change questionnaire.

Results

Intraclass correlation coefficients for limb symmetry index values ranged from .82 to .93. Standard errors of measurement were 3.04% to 5.59%. Minimal detectable changes, at the 90% confidence level, were 7.05% to 12.96%. Changes in hop test scores on the operative limb were statistically greater than changes on the nonoperative limb. Pearson correlations (r) between change in hop performances and self-reported measures ranged from .26 to .58.

Discussion and Conclusion

The results show that the described series of hop tests provide a reliable and valid performance-based outcome measure for patients undergoing rehabilitation following ACL reconstruction. These findings support the use and facilitate the interpretation of hop tests for research and clinical practice.
Florid histiocytic hemophagocytosis following therapy with long acting G‐CSF (pegfilgrastim)
Authors: Glasser Lewis , LeGolvan Mark , Horwitz Harold M.
Published: February 2007

We describe a case of histiocytic hemophagocytosis and increase in blasts in the bone marrow after administration of long acting G‐CSF (pegfilgrastim) in a 71‐year‐old man with underlying myelodysplasia. Pegfilgrastim was discontinued, with resolution of the hemophagocytosis and marked decrease in blasts from 30 to 5%. We postulate that pegfilgrastim provided a continuous stimulation of the monocyte/macrophage system, resulting in histiocytic hemophagocytosis. We recommend caution in defining indications for the use of long acting preparations of G‐CSF. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.
Igβ(CD79b) mRNA expression in chronic lymphocytic leukaemia cells correlates with immunoglobulin heavy chain gene mutational status but does not serve as an independent predictor of clinical severity
Authors: Cajiao Isabela , Sargent Rachel , Elstrom Rebecca , Cooke Nancy E. , Bagg Adam , Liebhaber Stephen A.
Published: February 2007

The etiology of chronic lymphocytic leukemia (CLL) is poorly understood and its course is highly variable. Somatic hypermutation (SHM) of the immunoglobulin heavy chain (IgVH) gene and ZAP70 protein expression have been reported as prognostic indicators. However, these assays are not widely available and their concordance is imperfect. Thus a need exists to identify additional molecular determinants of CLL. The Igβ (CD79b) subunit of the B cell antigen receptor is essential for B lymphocyte function. Defects in Igβ expression are implicated in CLL pathogenesis. We have analyzed Igβ mRNA expression in CLL cells in 40 consecutive patient samples. About 75% of the samples showed the expected decrease of Igβ surface staining. Igβ mRNA levels covered a wider range, did not correlate with Igβ surface staining, but clearly distinguished the normal and CLL lymphocyte populations. Remarkably, Igβ mRNA levels correlated strongly with SHM; Igβ mRNA levels in CLL cells were significantly higher in patients with an unmutated IgVH gene when compared with those in whom IgVH was hypermutated (P = 0.008). In contrast, no correlation was observed between Igβ mRNA levels and ZAP70 expression. Multiple parameters abstracted from chart reviews were used to estimate severity of CLL in each case. While severity correlated strongly with ZAP70 staining, and to a lesser extent with SHM status, there was no correlation with Igβ mRNA levels. These data establish a strong linkage between Igβ mRNA expression and SHM in CLL and highlight the complex relationships between biochemical parameters and clinical status in this disease. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.
Arteriovenous shunts in the human spleen
Authors: Barnhart Marion I. , Baechler Charles A. , Lusher Jeanne M.
Published: February 2007

The mission of this study was to determine whether or not arteriovenous connections, indicative of a “closed” type of circulation, existed in the human spleen. Spleens from four patients requiring therapeutic splenectomy were the basis for this report. Scanning electron microscopy of plastic corrosion casts, prepared from these four spleens, revealed direct vascular conduits between splenic pulp arteries or arterial capillaries and the venous sinuses in the red pulp. Also demonstrated were a few arteriovenous shunts between pulp arteries or arterial capillaries and pulp or trabecular veins. Inclusion of sized microspheres in low‐viscosity perfusion plastic illustrated that some diameters of the connecting shunts were 7‐10 μm, with other shunts even smaller. Not only do arteriovenous connections exist in human spleens, but their frequency, as revealed by methods accentuating three‐dimensional aspects of the splenic microcirculation, justify future reconsiderations of the functional significance of this closed type of circulation.

Examination of samples of the same intact spleens, prepared by freeze‐fracture and conventional critical‐point drying, also revealed an “open” type circulation structure, namely, pore‐patterned sinus walls that could facilitate blood cell movement from pulp cords into venous sinuses. Scanning electron microscopy thus has provided direct evidence that human spleens have both “open” and “closed” circulatory pathways in their microvasculature.
A view of the current status of antisickling therapy
Authors: Brewer George J.
Published: February 2007

About 5‐10 years ago it became popular to say that we understood the genetic and molecular basis for sickle cell anemia better than for any other disease and yet had no effective treatment. It was correctly pointed out that very little money was being spent at that time on sickle cell research relative to diseases of equal frequency which occur primarily in whites. The implication was that this contemporary financial and scientific neglect of the disease was a major reason for the lack of an adequate therapeutic approach. In the succeeding years a significant incremental amount of money was spent on sickle cell research, yet we still have no widely accepted antisickling* agent to offer sickle cell anemia patients. Sickle cell anemia has proven to be a formidable foe. These days, I hear molecular biologists frequently saying that if we could simply better understand the molecular mechanisms of sickle hemoglobin polymerization, we could surely design a drug which would be effective in preventing that process and would then have a therapy to offer patients. If the implication is that we should make our strongest efforts in the direction of hemoglobin polymerization and antipolymerization studies, I tend to disagree. A recent new insight offers hope for a different approach to the disease, one involving the red cell membrane, which I will briefly review. But first I wish to briefly review recent efforts at therapy and deal with some thoughts on why the frontal assault on sickle hemoglobin itself has not worked and probably will not work, at least for the near future.

Following the hypothesis of Murayama (1, 2) that polymerization of deoxyhemoglobin‐S molecules occurs because of hydrophobic bonding between molecules, Nalbandian et al. (3–5) began a search for agents which might interfere with this type of aggregation. They came up with urea and were able to show that urea inhibited and even reversed this area are in their infancy and need to be strongly pursued. Such a course, coupled with vigorous exploration of new insights into some of the complications of sickle cell anemia, may yet turn the tide in the not too distant future against this crippling disease.
Long‐term cytogenetic studies in acute leukemia of children; The nature of relapse
Authors: Zuelzer W. W. , Inoue Susumu , Thompson Ruby I. , Ottenbreit Mark J.
Published: February 2007

Sequential long‐term cytogentic studies in 71 children with acute leukemia were designed to investigate the nature of relapse after prolonged remission. In the overwhelming majority of the cases the findings suggested clonal identity of the leukemic cell population in relapse with that studied at the onset of the disease, notwithstanding considerable karyotypic instability in almost half of the patients. In a small minority an independent origin of the relapse clone could not be excluded on cytogenetic grounds but was considered unlikely, since mechanisms capable of accounting for the changes observed in these patients could be demonstrated in other cases. The persistence of diploid leukemic cells in the presence of an aneuploid subclone was demonstrated in the relapse bone marrow and/or spinal fluid in all active phases of the disease. On this basis the conversion from an aneuploid to a predominantly or exclusively diploid karyotype could be visualized, and a new model of clonal evolution, involving repetitive formation of abnormal karyotypes from a surviving diploid clone could be suggested.
Red cell values on the first postnatal day during the last 16 weeks of gestation
Authors: Zaizov Rina , Matoth Yehuda
Published: February 2007

The hemoglobin concentration, red cell count, hematocrit, reticulocyte count, and red cell size distribution were determined on skin prick blood obtained on the first postnatal day from infants born at various stages of gestation, from week 24 to term. During this period the hemoglobin concentration and hematocrit remained constant, around 19 gm/100 ml and 60%, respectively. The mean corpuscular volume decreased progressively, with a corresponding rise in the red cell count. The reticulocyte count decreased progressively from 9.6% to 3.7% during the period of observation. The red cell size distribution (Price Jones) curve was markedly shifted to the macrocytic side at 24–25 weeks. Thereafter, cells larger than 102 μ3 decreased gradually, while the percentage of smaller cells increased. These observations are not consistent with the hypothesis of a progressive decrease in the supply of oxygen to the fetus during the later stages of gestation, to which the fetus adapts by increasing its hemoglobin concentration.
Hereditary antithrombin iii deficiency and thromboembolic disease
Authors: Filip Donald J. , Eckstein John D. , Veltkamp Jan J.
Published: February 2007

Two teenage brothers with recurrent thromboembolic disease were found to have antithrombin III deficiency. A family study spanning four generations revealed a total of 10 members with antithrombin III deficiency. Five of the 10 affected family members have had thrombotic problems. Antithrombin III deficiency was documented by coagulation assays measuring heparin cofactor, anti‐Factor Xa, and progressive antithrombin activity; the level of antithrombin III antigenic material measured by immunoelectrophoresis was low in subjects with abnormal coagulation assays. The clinical features which may lead one to suspect the hereditary hypercoagulable condition of antithrombin III deficiency are reviewed.
Effect of sialidase on the viability of erythrocytes in circulation
Authors: Aminoff David , Bell William C. , Fulton Iia , Ingebrigtsen Nancy
Published: February 2007

Sialic acid has been detected on the erythrocyte surface of a number of different species of animals. The objective of this investigation was to determine the physiological significance of these sialyl residues to the viability of erythrocytes in circulation.

Methods have been described for the determination of total sialic acid on red blood cells and the conditions under which it may be released with sialidase. Chicken, dog, goat, and rabbit were chosen for these studies because of the differences in the amount (3 × 106‐72 × 106 residues per erythrocyte), and type (N‐acetyl‐ or N‐glycolyl‐neuraminic acids) of sialic acid found on the surface of their erythrocytes.

Radioactive tagging with Na2 51 CrO4 was used to monitor the effect of sialidase on the viability of erythrocytes upon autologous transfusion. By the two criteria used to assess the viability of erythrocytes — the percentage of erythrocytes surviving 24 hr after the autologous transfusion, and the half‐life of those red blood cells in circulation that survive the first 24 hr — it is apparent that the presence of sialic acid on the cell surface is crucial for the survival of nonnucleated mammalian erythrocytes. The loss of viability of dog erythrocytes can be elicited by the removal of approximately 10% of the total sialic acid. In marked contrast to the behavior of mammalian erythrocytes, sialidase‐treated chicken erythrocytes appear to retain their viability in circulation.
Erythropoietic precursors in mice with phenylhydrazine‐induced anemia
Authors: Hara Hiroshi , Ogawa Makio
Published: February 2007

Using a methylcellulose cell culture technique, we studied the serial changes in erythropoietic precursors in the femur, spleen, and blood of mice under erythropoietic stimuli. Phenylhydrazine hydrochloride, in the dosage of 60 mg/kg, was injected into mice subcutaneously on days 0, 1, and 3, and mice were sacrificed on days 0, 2, 4, 7, and 10 for assessment of erythropoietic precursors. Significant changes were observed for all hemopoietic organs in the number of erythrocytic burst‐forming units (BFU‐E) and erythrocytic colony‐forming units (CFU‐E). Only BFU‐E were present in blood, and their maximal increase was noted on day 2. While marrow BFU‐E continuously decreased, maximal increase of CFU‐E noted on day 4. Splenic BFU‐E and CFU‐E increased until day 4 and declined subsequently. These observations suggest the presence of significant migration of BFU‐E in mice under erythropoietic stimuli and stress the importance of studies on all hemopoietic organs in the assessment of murine hemopoiesis.
Detection of drug‐dependent antibodies by the 51cr platelet lysis test: Documentation of immune thrombocytopenia induced by diphenylhydantoin, diazepam, and sulfisoxazole
Authors: Cimo Philip L. , Pisciotta Anthony V. , Desai Rajendra G. , Pino Jose L. , Aster Richard H.
Published: February 2007

Sudden, severe thrombocytopenia developed in each of three patients receiving diphenylhydantoin, diazepam, and sulfisoxazole, respectively. Recovery followed discontinuance of the drugs. An antiplatelet antibody requiring the presence of an appropriate drug for interaction with platelets was demonstrated in each case by the 51Cr platelet lysis test using normal, paroxysmal nocturnal hemoglobinuric, or enzyme‐treated normal platelets as target cells. These antibodies could not be detected by techniques that depend on clot retraction inhibition, complement fixation, or platelet factor‐3 activation. Quinine‐ and quinidine‐dependent antiplatelet antibodies in the serum of 16 patients who developed acute thrombocytopenia while taking either quinine or quinidine could be demonstrated readily with the 51Cr platelet lysis test and could also be detected by other methods employed.
Chronic lymphocytic leukemia: Correlation of clinical course and therapeutic response with in vitro testing and morphology of lymphocytes
Authors: Knospe William H. , Gregory Stephanie Ann , Trobaugh Frank E. , Stedronsky Judith A. , Schrek Robert
Published: February 2007

Forty‐two patients with chronic lymphocytic leukemia (CLL) were studied for morphology of lymphocytes by light and electron microscopy (EM), in vitro responses of lymphocytes to a battery of physical and chemical agents, overall clinical status, immunologic status, course, and response to therapy. CLL lymphocytes could be classified by EM into four groups on the basis of cell size and nuclear contour and by light microscopy into two groups, small cells and large cells (lymphosarcoma cells). Patient survival did not vary with cell size or morphology as determined by light or electron microscopy. In vitro testing of CLL lymphocytes following exposure to x‐ray, PHA, DMSO 2 hr at 43°, prednisolone, glutaminase, and asparaginase permitted a separation of patients into categories of normal and abnormal in vitro responses. A normal in vitro response predicted a good response to therapy but an abnormal in vitro response did not preclude a good response to therapy. Following therapy, normalization of abnormal EM morphology and in vitro response was seen in some patients. Most patients tested had decreased serum immunoglobulins and abnormal PHA responses. There was a high incidence of infections and second neoplasms. Immunologic deficits could not be correlated with variations in lymphocyte morphology or in vitro response.
A chlorpromazine‐induced inhibitor of blood coagulation
Authors: Canoso Rosa T. , Hutton Ronald A. , Deykin Daniel
Published: February 2007

An inhibitor of blood coagulation was detected in the plasma of four schizophrenic patients receiving long‐term chlorpromazine therapy. The partial thromboplastin time (PTT) was prolonged in all four patients and the prothrombin time (PT) was prolonged in one. The inhibitor which resembled in many respects that seen in patients with systemic lupus erythematosus (SLE) was shown to be associated with the IgM‐rich fractions of the serum. None of the patients manifested a clinical bleeding tendency and in two, discontinuation of the chlorpromazine was followed by a decrease in the activity of the anticoagulant. While three of the patients had a positive antinuclear antibody test (ANA) and the fourth a false positive serology for syphilis, no further evidence for SLE was found.