bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological Characterization of an Adenylyl Cyclase-Coupled 5-HT Receptor inAplysia: Comparison With Mammalian 5-HT Receptors
Authors: Cohen Jonathan E. , Onyike Chiadi U. , McElroy Virginia L. , Lin Allison H. , Abrams Thomas W.
Published: May 2006

We attempted to identify compounds that are effective in blocking the serotonin (5-hydroxytryptamine, 5-HT) receptor(s) that activate adenylyl cyclase (AC) in Aplysia CNS. We call this class of receptor 5-HTapAC. Eight of the 14 antagonists tested were effective against 5-HTapACin CNS membranes with the following rank order of potency: methiothepin > metergoline ∼ fluphenazine > clozapine > cyproheptadine ∼ risperidone ∼ ritanserin > NAN-190. GR-113808, olanzapine, Ro-04-6790, RS-102221, SB-204070, and spiperone were inactive. Methiothepin completely blocked 5-HT stimulation of AC with a Kbof 18 nM. Comparison of the pharmacological profile of the 5-HTapACreceptor with those of mammalian 5-HT receptor subtypes suggested it most closely resembles the 5-HT6receptor. AC stimulation in Aplysia sensory neuron (SN) membranes was also blocked by methiothepin. Methiothepin substantially inhibited two effects of 5-HT on SN firing properties that are mediated by a cAMP-dependent reduction in S-K+current: spike broadening in tetraethylammonium/nifedipine and increased excitability. Consistent with cyproheptadine blocking 5-HT stimulation of AC, cyproheptadine also blocked the 5-HT-induced increase in SN excitability. Methiothepin was less effective in blocking AC-mediated modulatory effects of 5-HT in electrophysiological experiments on SNs than in blocking AC stimulation in CNS or SN membranes. This reduction in potency appears to be due to effects of the high ionic strength of physiological saline on the binding of this antagonist to the receptor. Methiothepin also antagonized AC-coupled dopamine receptors but not AC-coupled small cardioactive peptide receptors. In conjunction with other pharmacological probes, this antagonist should be useful in analyzing the role of 5-HT in various forms of neuromodulation in Aplysia.
Putaminal Activity for Simple Reactions or Self-Timed Movements
Authors: Lee Irwin H. , Assad John A.
Published: May 2006

To examine the role of basal ganglia-cortical circuits in movement initiation, we trained monkeys to make the same arm movements in two ways—in immediate reaction to a randomly timed external cue (cued movements) and also following a variable delay without an explicit initiation signal (self-timed movements). The two movement types were interleaved and balanced in overall timing to allow a direct comparison of activity before and during the movement. Posterior putaminal neurons generally had phasic, movement-related discharges that were comparable for cued and self-timed movements. On cued movements, neuronal activity increased sharply following cue onset. However, for self-timed movements, there was a slow build-up in activity that preceded the phasic discharge. This slow build-up was time-locked to movement and restricted to a narrow time window hundreds of milliseconds before movement. The difference in premovement activity between cued and self-timed trials was present before the earliest cue-onset times and was not related to any differences in the overall time-to-move between the two types of trials. These features suggest that activity evolving in the basal ganglia-cortical circuitry may drive the initiation of movements by increasing until an activity threshold is exceeded. The activity may increase abruptly in response to an external cue or gradually when the timing of movements is determined by the animals themselves rather than an external cue. In this view, small changes in activity that occur in advance of the much larger perimovement neuronal activity may be an important determinant of when movement occurs. In support of this hypothesis, we found that even for cued movements, faster reaction times were associated with slightly higher levels of activity hundreds of milliseconds before movement.
Activity in the Parabigeminal Nucleus During Eye Movements Directed at Moving and Stationary Targets
Authors: Cui He , Malpeli Joseph G.
Published: May 2006

The parabigeminal nucleus (PBN) is a small satellite of the superior colliculus located on the edge of the midbrain. To identify activity related to visuomotor behavior, we recorded from PBN cells in cats trained to fixate moving and stationary targets. Cats tracked moving targets primarily with small catch-up saccades, and for target speeds of 2–6°/s, they did so with sufficient accuracy to keep targets within 2.5° of the visual axis most of the time. During intersaccade intervals of such close-order tracking, PBN cells fired at rates related to retinal position error (RPE), the distance between the center of the retina and the saccade target. Each cell was characterized by a best direction of RPE. Most commonly, activity rose rapidly with increasing RPE, peaked at a small RPE within the area centralis, and dropped off gradually with increasing target distance. For some cells, the range over which activity was monotonically related to RPE was considerably larger, but because the PBN was not systematically sampled, the maximum range of RPE encoded is presently unknown. During saccades, activity began to change at about peak saccade velocity and then rapidly reached a level appropriate to the RPE achieved at saccade end. Most response fields were large, and stationary saccade targets presented anywhere within them evoked brisk responses that terminated abruptly on saccade offset. Spontaneous saccades in the dark had little effect on PBN activity. These data suggest that the PBN is an integral part of a midbrain circuit generating target location information.
Nature of Variability in Saccades
Authors: Smeets Jeroen B. J. , Hooge Ignace T. C.
Published: May 2006

We studied the variability in saccades by comparing the peak velocities of saccades with the same target amplitude made with different actual amplitudes. We tested three hypotheses: the pulse-height noise hypothesis (peak velocity and amplitude vary proportionally), the localization noise hypothesis (variability in amplitude and peak velocity lie along the main sequence), and the independent noise hypothesis (variability in amplitude and peak velocity are independent). We measured eye orientation in two experiments by a scleral coil and a video system. Surprisingly, the main source of variability of saccades depended on the measurement system used. A combination of localization noise and independent noise best describes the data obtained by the video system. The independent noise (e.g., measurement inaccuracy) was the main source of variability. For the scleral coils, the variability was considerably larger than for the less accurate video system. The pulse-height noise hypothesis best describes this additional variability. Therefore we conclude that pulse-height noise is the main source of variability in saccades measured with scleral coils. We discuss the influence of scleral coils on saccade generation and suggest that a change in motor strategy due to the discomfort of wearing the coils might be the cause of the increased variability.
Orexin-A Depolarizes Nucleus Tractus Solitarius Neurons Through Effects on Nonselective Cationic and K+ Conductances
Authors: Yang Bo , Ferguson Alastair V.
Published: May 2006

The nucleus tractus solitarius (NTS) plays central roles in a number of autonomic functions including cardiovascular control. Orexin (ORX)-A is a 33-amino-acid peptide implicated in the central regulation of energy metabolism, sleep, and the cardiovascular system. Studies demonstrate the presence of ORX-immunoreactive axons and both OX1R (orexin receptor) and OX2R mRNA within NTS. In this study, whole cell patch-clamp recordings were obtained from NTS neurons in rat medullary slices. Current-clamp studies showed that bath application of various concentrations of ORX-A depolarized 90.7% (78 of 86) of neurons tested while the remaining cells were either unaffected or showed small hyperpolarizations in response to peptide administration. Depolarizing effects were maintained in the presence of 5 μM TTX, and were concentration dependent. Using voltage-clamp techniques, we also identified modulatory actions of ORX-A on specific ion channels. Our results demonstrate that not only does ORX-A inhibit a specific potassium conductance (the sustained K+ current) in NTS neurons, but it also activates a nonselective cationic conductance (NSCC). These data suggest that ORX-A effects on central cardiovascular control may result from direct actions on NTS neurons and also highlight the ability of this peptide to influence neuronal excitability as a consequence of concurrent modulation of multiple ion channels.
Kappa Opioid Receptor Activation in the Nucleus Accumbens Inhibits Glutamate and GABA Release Through Different Mechanisms
Authors: Hjelmstad Gregory O. , Fields Howard L.
Published: May 2006

Through their actions in the nucleus accumbens (NAc), kappa opioid (KOP) receptors and their endogenous ligand, dynorphin, modify behaviors associated with the administration of drugs of abuse and are regulated by exposure to such drugs. Despite their demonstrated behavioral significance, the synaptic actions of KOP receptor ligands in the NAc are not clearly understood. Using whole-cell voltage-clamp recordings of NAc medium spiny neurons, we have found that, in addition to suppressing glutamate release, the KOP receptor agonist U69593 also inhibits GABA release. Interestingly, the mechanism of inhibition of the release of glutamate differs from that controlling GABA. U69593 reduces the frequency of Ca2+-independent miniature excitatory postsynaptic currents, but not miniature inhibitory postsynaptic currents. Furthermore, while the U69593 inhibition of GABAergic transmission is blocked by the N-type Ca2+channel blocker ω-CgTx, the inhibition of excitatory glutamatergic transmission by U69593 is unaffected by N-type Ca2+ channel blockade. These results indicate that KOP receptor activation inhibits GABA release by reducing Ca2+ influx, but inhibits glutamate release at a step downstream of Ca2+entry.
Glycinergic Inputs to Cardiac Vagal Neurons in the Nucleus Ambiguus Are Inhibited by Nociceptin and μ-Selective Opioids
Authors: Venkatesan Priya , Baxi Sunit , Evans Cory , Neff Robert , Wang Xin , Mendelowitz David
Published: May 2006

Most parasympathetic regulation of heart rate originates from preganglionic cardiac vagal neurons within the nucleus ambiguus. Little is known regarding the modulation of glycinergic transmission to these neurons. However, the presence of μ-opioid receptors and opioid-receptor-like (ORL1) receptors within the ambiguus, together with the presence of endogenous ligands for both receptor types in the same area, suggests opioids may modulate synaptic transmission to cardiac vagal neurons. This study therefore examined the effects of endomorphin-1 and endomorphin-2 (the μ-selective endogenous peptides), DAMGO (a synthetic, μ-selective agonist), and nociceptin (the ORL1-selective endogenous peptide) on spontaneous glycinergic inhibitory postsynaptic currents (IPSCs) in rat cardiac parasympathetic neurons. All four of the opioids used in this study decreased spontaneous IPSCs. At concentrations of 100 μM, the amplitude of the IPSCs was reduced significantly by nociceptin (–56.6%), DAMGO (–46.5%), endomorphin-1 (–45.1%), and endomorphin-2 (–26%). IPSC frequency was also significantly reduced by nociceptin (–61.1%), DAMGO (–69.9%), and endomorphin-1 (–40.8%) but not endomorphin-2. Lower concentrations of nociceptin and DAMGO (10–30 μM) also effectively decreased IPSC amplitude and frequency. The inhibitory effects of DAMGO were blocked by d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2(C-TOP; 10 μM), a selective μ-receptor antagonist. Neither nociceptin nor DAMGO inhibited the postsynaptic responses evoked by exogenous application of glycine or affected TTX-insensitive glycinergic mini-IPSCs. These results indicate that μ-selective opioids and nociceptin act on preceding neurons to decrease glycinergic inputs to cardiac vagal neurons in the nucleus ambiguus. The resulting decrease in glycinergic transmission would increase parasympathetic activity to the heart and may be a mechanism by which opioids induce bradycardia.
Band-Pass Response Properties of Rat SI Neurons
Authors: Garabedian Catherine E. , Jones Stephanie R. , Merzenich Michael M. , Dale Anders , Moore Christopher I.
Published: May 2006

Rats typically employ 4- to 12-Hz “whisking” movements of their vibrissae during tactile exploration. The intentional sampling of signals in this frequency range suggests that neural processing of tactile information may be differentially engaged in this bandwidth. We examined action potential responses in rat primary somatosensory cortex (SI) to a range of frequencies of vibrissa motion. Single vibrissae were mechanically deflected with 5-s pulse trains at rates ≤40 Hz. As previously reported, vibrissa deflection evoked robust neural responses that consistently adapted to stimulus rates ≥3 Hz. In contrast with this low-pass feature of the response, several other characteristics of the response revealed bandpass response properties. While average evoked response amplitudes measured 0–35 ms after stimulus onset typically decreased with increasing frequency, the later components of the response (>15 ms post stimulus) were augmented at frequencies between 3 and 10 Hz. Further, during the steady state, both rate and temporal measures of neural activity, measured as total spike rate or vector strength (a measure of temporal fidelity of spike timing across cycles), showed peak signal values at 5–10 Hz. A minimal biophysical network model of SI layer IV, consisting of an excitatory and inhibitory neuron and thalamocortical input, captured the spike rate and vector strength band-pass characteristics. Further analyses in which specific elements were selectively removed from the model suggest that slow inhibitory influences give rise to the band-pass peak in temporal precision, while thalamocortical adaptation can account for the band-pass peak in spike rate. The presence of these band-pass characteristics may be a general property of thalamocortical circuits that lead rodents to target this frequency range with their whisking behavior.
The Ability to Negotiate or the Ability to Love?
Authors: Carroll Jason S. , Badger Sarah , Yang Chongming
Published: May 2006

Drawing from developmental theories of interpersonal competence, this article presents a multidimensional model of marital competence and reports on a study that provides a preliminary evaluation of the model and its central tenets. Structural equation modeling analyses were run with a nationally representative sample of 750 couples to test the model. The results demonstrated that the model accounted for 65% to 67% of the variance in partners' relationship quality and provided initial support to the theoretical and empirical utility of distinguishing marital competence according to developmentally defined domains of intrapersonal and interpersonal competencies. Implications of these findings for research and intervention are discussed.
National audit of post-operative management in spinal surgery
Authors: McGregor Alison H , Dicken Ben , Jamrozik Konrad
Published: May 2006

Background

There is some evidence from a Cochrane review that rehabilitation following spinal surgery may be beneficial.

Methods

We conducted a survey of current post-operative practice amongst spinal surgeons in the United Kingdom in 2002 to determine whether such interventions are being included routinely in the post-operative management of spinal patients.

The survey included all surgeons who were members of either the British Association of Spinal Surgeons (BASS) or the Society for Back Pain Research. Data on the characteristics of each surgeon and his or her current pattern of practice and post-operative care were collected via a reply-paid postal questionnaire.

Results

Usable responses were provided by 57% of the 89 surgeons included in the survey. Most surgeons (79%) had a routine post-operative management regime, but only 35% had a written set of instructions that they gave to their patients concerning this. Over half (55%) of surgeons do not send their patients for any physiotherapy after discharge, with an average of less than two sessions of treatment organised by those that refer for physiotherapy at all. Restrictions on lifting, sitting and driving showed considerable inconsistency both between surgeons and also within the recommendations given by individual surgeons.

Conclusion

Demonstrable inconsistencies within and between spinal surgeons in their approaches to post-operative management can be interpreted as evidence of continuing and significant uncertainty across the sub-speciality as to what does constitute best care in these areas of practice. Conducting further large, rigorous, randomised controlled trials would be the best method for obtaining definitive answers to these questions.
Quality of life and hormone use: new validation results of MRS scale
Authors: Dinger Jürgen , Zimmermann Thomas , Heinemann Lothar AJ , Stoehr Diana
Published: May 2006

Background

The Menopause Rating Scale is a health-related Quality of Life scale developed in the early 1990s and step-by-step validated since then. Recently the MRS scale was validated as outcomes measure for hormone therapy. The suspicion however was expressed that the data were too optimistic due to methodological problems of the study. A new study became available to check how founded this suspicion was.

Method

An open post-marketing study of 3282 women with pre- and post- treatment data of the self-administered version of the MRS scale was analyzed to evaluate the capacity of the scale to detect hormone treatment related effects with the MRS scale. The main results were then compared with the old study where the interview-based version of the MRS scale was used.

Results

The hormone-therapy related improvement of complaints relative to the baseline score was about or less than 30% in total or domain scores, whereas it exceeded 30% improvement in the old study. Similarly, the relative improvement after therapy, stratified by the degree of severity at baseline, was lower in the new than in the old study, but had the same slope. Although we cannot exclude different treatment effects with the study method used, this supports our hypothesis that the individual MRS interviews performed by the physician biased the results towards over-estimation of the treatment effects. This hypothesis is underlined by the degree of concordance of physician's assessment and patient's perception of treatment success (MRS results): Sensitivity (correct prediction of the positive assessment by the treating physician) of the MRS and specificity (correct prediction of a negative assessment by the physician) were lower than the results obtained with the interview-based MRS scale in the previous publication.

Conclusion

The study confirmed evidence for the capacity of the MRS scale to measure treatment effects on quality of life across the full range of severity of complaints before treatment. The difference of the relative improvement after therapy between the old and current study as well as the observed different sensitivity/specificity is – as a matter of probability – more likely to be caused by a bias introduced by the different application of the MRS scale than by real differences in the efficacy of the therapy. A randomized clinical trial would be needed to test the impact of the latter. The message for future studies is: The MRS scale should be only used as self-administered tool where the suggestive effect of questions raised by health professionals ("therapeutic optimism") can be largely excluded.
PI3K signaling and miRNA expression during the response of quiescent human fibroblasts to distinct proliferative stimuli
Authors: Gu Jian , Iyer Vishwanath R
Published: May 2006

Background

Serum treatment of quiescent human dermal fibroblasts induces proliferation, coupled with a complex physiological response that is indicative of their normal role in wound-healing. However, it is not known to what extent such complex transcriptional events are specific to a given cell type and signal, and how these global changes are coordinately regulated. We have profiled the global transcriptional program of human fibroblasts from two different tissue sources to distinct growth stimuli, and identified a striking conservation in their gene-expression signatures.

Results

We found that the wound-healing program of gene expression was not specific to the response of dermal fibroblasts to serum but was regulated more broadly. However, there were specific differences among different stimuli with regard to signaling pathways that mediate these transcriptional programs. Our data suggest that the PI3-kinase pathway is differentially involved in mediating the responses of cells to serum as compared with individual peptide growth factors. Expression profiling indicated that let7 and other miRNAs with similar expression profiles may be involved in regulating the transcriptional program in response to proliferative signals.

Conclusion

This study provides insights into how different stimuli use distinct as well as conserved signaling and regulatory mechanisms to mediate genome-wide transcriptional reprogramming during cell proliferation. Our results indicate that conservation of transcriptional programs and their regulation among different cell types may be much broader than previously appreciated.
Dynamics of CD81 expression on lymphocyte subsets during interferon-α-based antiviral treatment of patients with chronic hepatitis C
Authors: Kronenberger Bernd , Herrmann Eva , Hofmann W Peter , Wedemeyer Heiner , Sester Martina , Mihm Ulrike , Ghaliai Temam , Zeuzem Stefan , Sarrazin Christoph
Published: May 2006

CD81 is a hepatitis C virus (HCV) coreceptor with important functions in lymphocytes. During treatment, CD81 expression may be changed directly by the antiviral therapy or indirectly by reduction of the HCV serum level. The regulation of CD81 on lymphocyte subtypes has not been investigated so far and may be relevant for the control of viral infection and treatment response. CD81 was analyzed by flow cytometry in CD8(+), CD4(+), CD19(+), and CD56(+) lymphocyte subtypes from 20 patients with chronic hepatitis C before, during, and after antiviral treatment with pegylated interferon-α (IFN-α) and ribavirin. A sustained virologic response (SVR) was achieved in 11 patients. Dynamics of CD81 were investigated in correlation with HCV-RNA dynamics and the outcome of therapy. During treatment, the following typical patterns of CD81 regulation were observed: down-regulation on CD8(+) T cells (P=0.022) and most significantly, on CD56(+) natural killer cells (P<0.001), transient up-regulation on CD19(+) B cells (P=0.006), and weak and late down-regulation on CD4(+) T cells (P=0.028). During treatment, CD81 expression was not associated with the HCV-RNA serum level on all lymphocyte subtypes. After end of treatment, CD81 increased again in CD8(+) and CD56(+) cells (P=0.001, P=0.002). On CD8(+) T cells post-treatment, CD81 remained lower in patients who achieved a SVR compared with patients who failed to eliminate HCV after treatment (P=0.033). Lymphocyte subsets show different patterns of CD81 response before and during antiviral treatment, which are associated with administration of IFN-α and antiviral response.
Contrasting perspectives on globalization and labour in South Africa
Authors: Jenkins Rhys
Published: May 2006

The academic analysis of the labour market impacts of globalization has been dominated by neoclassical approaches both in the extensive work on developed countries and the more limited, but growing literature on developing countries. However, in many developing countries the positive impacts predicted for workers in (unskilled) labour-abundant economies have not been observed. This suggests that heterodox approaches may have an important contribution to make in analysing labour market outcomes. The paper contrasts the neoclassical and heterodox interpretations, reviews previous empirical studies of South Africa, and presents new data and analysis of the South African manufacturing sector.
Health-Related Quality of Life Among Child and Adolescent Survivors of Childhood Cancer
Authors: Speechley Kathy N. , Barrera Maru , Shaw Amanda K. , Morrison Howard I. , Maunsell Elizabeth
Published: May 2006

Purpose

The main objective was to compare parent-reported health-related quality of life (HRQL) of child and adolescent survivors of childhood cancer to that of controls who had no history of cancer.

Methods

We assessed HRQL of 800 child and adolescent survivors younger than 16 years and 923 randomly selected, age- and sex-matched controls from the general population in a national multicenter retrospective cohort study using the Child Health Questionnaire parent report. Participation was 69% among survivors and 57% among controls.

Results

Survivors had means that were consistently lower than controls on the HRQL physical summary (PH; 49.9 v 55.3; P <.005), psychosocial summary (PS; 49.4 v 52.6; P < .005), and all but one of the eight subscale scores. Clinically important survivor-control differences in means on PH were found for survivors of CNS tumors, bone tumors, lymphoma, leukemia, soft tissue sarcoma and Wilms' tumor (differences: −8.7, −7.0, −6.3, −5.4, −4.4, −3.8/100, respectively); on PS, survivors of CNS tumors were most compromised (−6.1/100). Survivor-control differences in both PH and PS were also large for survivors treated with radiation only (−5.8 and −11.9/100, respectively), or radiation combined with surgery (−6.6 and −5.9/100, respectively), or radiation combined with both surgery and chemotherapy (−7.8 and −5.1/100, respectively). Cranial radiation was associated with the most compromised HRQL.

Conclusion

According to parents, HRQL for survivors was somewhat poorer, overall, than for controls. Survivors of CNS tumors, lymphoma, and leukemia and those patients treated with cranial radiation were reported to have poorest HRQL. These findings support development of guidelines for levels of follow-up care for particular groups of survivors.
Where Does Hematology End and Oncology Begin? Questions of Professional Boundaries and Medical Authority
Authors: Krueger Gretchen , Canellos George
Published: May 2006

This article recounts the development of the American Society of Clinical Oncology (ASCO) and explores the role of its members in defining oncology's boundaries—boundaries dictated by scientific innovations, major changes in the structure of medical specialization, and the competing efforts of closely related professional groups. Oral histories, journal articles, and unpublished materials from the ASCO History of Oncology Archive were reviewed to analyze these events closely. In 1972, the American Board of Internal Medicine recognized medical oncology as a subspecialty, creating tensions between oncology and hematology as each discipline defended its identity. Drawing on sources produced by hematologists, historian Keith Wailoo (Wailoo, Drawing Blood, 1997) has shown that when medical oncologists claimed wide-ranging expertise over the treatment of all patients suffering from malignant disease in their pursuit of specialty status, the leukemias became contested ground. This article extends this thesis by reviewing the central role of ASCO in these events and recreating the dialogue between members of the two fields as they sought recognition at individual institutions and, more broadly, within American medicine. By acknowledging the contestation of its authority and the results of these prolonged negotiations, we can better understand the current status of oncology and its future outlook.
Adjuvant Aromatase Inhibitors for Early Breast Cancer After Chemotherapy-Induced Amenorrhoea: Caution and Suggested Guidelines
Authors: Smith Ian E. , Dowsett Mitch , Yap Yoon-Sim , Walsh Geraldine , Lønning Per E. , Santen Richard J. , Hayes Daniel
Published: May 2006

Purpose

Aromatase inhibitors (AIs) are now established as adjuvant therapy for early hormone receptor–positive breast cancer in postmenopausal women. Their use is sometimes extended to younger women after chemotherapy-induced amenorrhoea; we have audited this in one institution's breast unit, and we propose guidelines for use in such circumstances.

Patients and Methods

The use of aromatase inhibitors as adjuvant therapy in younger women age ≥ 40 with hormone receptor–positive early breast cancer and chemotherapy-induced amenorrhea has been audited clinically and biochemically.

Results

A total of 45 such women were identified in the audit, with a median age of 47 years (range, 39 to 52 years). Twelve women (27%) showed a return of ovarian function (10 renewed menses, one pregnancy, one biochemically premenopausal) after starting an AI. Median age at restart of ovarian function was 44 years (range, 40 to 50 years).

Conclusion

AIs may promote recovery of ovarian function in some women with chemotherapy-induced amenorrhea and should be used with caution. Biochemical monitoring of ovarian function requires highly sensitive immunoassays. Guidelines for the selection and delivery of adjuvant endocrine therapy in such patients are proposed.
Continuous Methimazole Therapy and Its Effect on the Cure Rate of Hyperthyroidism Using Radioactive Iodine: An Evaluation by a Randomized Trial
Authors: Bonnema Steen Joop , Bennedbæk Finn Noe , Veje Annegrete , Marving Jens , Hegedüs Laszlo
Published: May 2006

Background: A randomized clinical trial was performed to clarify whether continuous use of methimazole (MTZ) during radioiodine (131I) therapy influences the final outcome of this therapy.

Design: Consecutive patients with Graves’ disease (n = 30) or a toxic nodular goiter (n = 45) were rendered euthyroid by MTZ and randomized to stop MTZ 8 d before 131I (−MTZ; n = 36) or to continue MTZ until 4 wk after 131I (+MTZ; n = 39). Calculation of the 131I activity included an assessment of the 131I half-life and the thyroid volume.

Results: The 24-h thyroid 131I uptake was lower in the +MTZ group than in the −MTZ group (44.8 ± 15.6% vs. 62.1 ± 9.9%, respectively; P < 0.001). At 3 wk after therapy, no significant change in serum free T4 index was observed in the +MTZ group (109 ± 106 vs. 83 ± 28 nmol/liter at baseline; P = 0.26), contrasting an increase in the −MTZ group (180 ± 110 vs. 82 ± 26 nmol/liter; P < 0.001). The number of cured patients was 17 (44%) and 22 (61%) in the +MTZ and −MTZ groups, respectively (P = 0.17). Cured patients tended to have a lower 24-h thyroid 131I uptake (50.1 ± 13.8% vs. 56.4 ± 17.1%; P = 0.09). By adjusting for a possible interfactorial relationship through a regression analysis (variables: randomization, 24- and 96-h thyroid 131I uptake, type and duration of disease, age, gender, presence of antithyroid peroxidase antibodies, thyroid volume, dose of MTZ), only the continuous use of MTZ correlated with treatment failure (P = 0.006), whereas a low 24-h thyroid 131I uptake predicted a better outcome (P = 0.006).

Conclusion: Continuous use of MTZ hinders an excessive increase of the thyroid hormones during 131I therapy of hyperthyroid diseases. However, such a strategy seems to reduce the final cure rate, although this adverse effect paradoxically is attenuated by the concomitant reduction of the thyroid 131I uptake.
Dual-Optimal Inequalities for Stabilized Column Generation
Authors: Ben Amor Hatem , Desrosiers Jacques , Valério de Carvalho José Manuel
Published: May 2006

Column generation is one of the most successful approaches for solving large-scale linear programming problems. However, degeneracy difficulties and long-tail effects are known to occur as problems become larger. In recent years, several stabilization techniques of the dual variables have proven to be effective. We study the use of two types of dual-optimal inequalities to accelerate and stabilize the whole convergence process. Added to the dual formulation, these constraints are satisfied by all or a subset of the dual-optimal solutions. Therefore, the optimal objective function value of the augmented dual problem is identical to the original one. Adding constraints to the dual problem leads to adding columns to the primal problem, and feasibility of the solution may be lost. We propose two methods for recovering primal feasibility and optimality, depending on the type of inequalities that are used. Our computational experiments on the binary and the classical cutting-stock problems, and more specifically on the so-called triplet instances, show that the use of relevant dual information has a tremendous effect on the reduction of the number of column generation iterations.
Difference in Risks of Allergic Reaction to Sulfonamide Drugs Based on Chemical Structure
Authors: Verdel B Marianne , Souverein Patrick C , Egberts Antoine CG , Leufkens Hubert GM
Published: May 2006

Background:

The chemical structure of sulfonamide antibiotics and sulfonamide nonantibiotics can affect the potential for adverse reactions.

Objective:

To assess whether differences in chemical structure of the various sulfonamide drugs influence the risk of allergic events.

Methods:

A case–control study was conducted among patients with diabetes mellitus (DM) using data from the General Practice Research Database. Cases were defined as patients with a diagnosis of hypersensitivity or allergic reaction. The date of the last event was the index date. Controls were matched on practice, type of DM, and index date. Current use of sulfonamides was defined as use in a 14 day time window before the index date. Sulfonamides were classified according to the presence/absence of an N1 substituent (N1+/-) and/or an arylamine (N4+/-). Conditional logistic regression was used to estimate strength of association and expressed as odds ratios and 95% confidence intervals.

Results:

Overall, current use of N1+ N4+ sulfonamide drugs was associated with the outcome (adjusted OR 3.71; 95% Cl 1.40 to 9.81). Current use of N1+ N4- and N1- N4- sulfonamide drugs was also associated with the occurrence of allergic reactions, although not as strongly: adjusted OR 2.48 (95% Cl 2.12 to 2.89) and 2.07 (95% Cl 1.74 to 2.46), respectively. Sex and age seemed to be effect modifiers. There was no clear evidence for effect modification by immune disease state.

Conclusions:

Although we did not identify major differences between the groups, we believe that this approach is an innovative manner to examine adverse drug reactions by using chemical structure instead of therapeutic drug classes to classify exposure.
Irrational categorization, natural intolerance and reasonable discrimination: Lay representations of prejudice and racism
Authors: Figgou Lia , Condor Susan
Published: May 2006

This paper explores how the constructs of ‘prejudice’ and ‘racism’ were used and understood by respondents in an interview study concerning the settlement of Albanian refugees in Greece. Analysis indicated the existence of multiple, potentially contradictory, common sense understandings of prejudice and racism, analogous to some accounts of the prejudice construct in academic social psychology. However, notwithstanding the fact that respondents displayed multiple understandings of racism or prejudice in theory, these abstract formulations were rarely employed to account for actual instances of discrimination. Specific discriminatory acts against Albanian people were framed instead as matters of fear and risk. By virtue of being cast within a problematic of in/security rather than within the discursive frame of prejudice, particular hostile actions against the Albanian refugees could be glossed as reasonable and understandable.
Prosocials prefer equal outcomes to maximizing joint outcomes
Authors: Eek Daniel , Gärling Tommy
Published: May 2006

Existing theories of social value orientations posit that prosocials maximize joint outcomes whereas proselfs maximize outcomes to themselves. Three studies employing a total of 157 undergraduates were conducted to test the alternative hypothesis that prosocials prefer equal outcomes to maximizing joint outcome. In study 1 participants completed the Triple‐Dominance Measure of Social Values in which a fourth alternative that distributed the largest joint outcome unequally was added to the alternative that distributed the outcomes equally. In accordance with the hypothesis, prosocials preferred the equal‐outcome alternative to the joint‐outcome alternative. Study 2 confirmed and extended these results by demonstrating that prosocials preferred equal outcomes to larger joint outcomes that were unequally distributed but provided both with larger outcomes. Study 3 demonstrated that in a modified prisoner's dilemma game, a preference for equal outcomes to a larger joint outcome resulted in that prosocials cooperated when they believed or knew that the other cooperated, and defected when they believed or knew that the other defected.
Long-Term Potentiation Enhances Neurogenesis in the Adult Dentate Gyrus
Authors: Bruel-Jungerman Elodie , Davis Sabrina , Rampon Claire , Laroche Serge
Published: May 2006

Activity-dependent synaptic plasticity and neurogenesis are two forms of brain plasticity that can participate in functional remodeling of neural networks during the formation of memories. We examined whether long-term potentiation (LTP) of excitatory synaptic transmission, a well characterized form of synaptic plasticity believed to play a critical role in memory formation, can regulate the rate of neurogenesis in the adult rat dentate gyrusin vivo. We first show that induction of LTP at medial perforant path–granule cell synapses stimulates the proliferation of progenitor cells in the dentate gyrus with a consequential long-term persistence of a larger population of surviving newborn cells. Using protocols to examine the effect of LTP on survival, we next show that LTP induction promotes survival of 1- to 2-week-old dentate granule cells. In no case did LTP appear to affect neuronal differentiation. Finally, we show that LTP induces expression of the plasticity-related transcription factor Zif268 in a substantial fraction of 2-week-old but not 1-week-old neurons, suggesting the prosurvival effect of LTP can be observed in the absence of LTP-mediated Zif268 induction in newborn cells. Our results indicate that electrically induced LTP in the dentate gyrusin vivoprovides a cellular/molecular environment that favors both proliferation and survival of adult-generated neurons.
Otx2 Controls Identity and Fate of Glutamatergic Progenitors of the Thalamus by Repressing GABAergic Differentiation
Authors: Puelles Eduardo , Acampora Dario , Gogoi Robindra , Tuorto Francesca , Papalia Alessandro , Guillemot Francois , Ang Siew-Lan , Simeone Antonio
Published: May 2006

GABAergic and glutamatergic neurons modulate inhibitory and excitatory networks in the CNS, and their impairment may cause neurological and psychiatric disorders. Thus, understanding the molecular mechanisms that control neurotransmitter phenotype and identity of excitatory and inhibitory progenitors has considerable relevance. Here we investigated the consequence of Otx2 (orthodenticle homolog) ablation in glutamatergic progenitors of the dorsal thalamus (referred to as thalamus). We report that Otx2 is cell-autonomously required in these progenitors to repress GABAergic differentiation. Our data indicate that Otx2 may prevent GABAergic fate switch by repressing the basic helix–loop–helix geneMash1(mammalian achaete-schute homolog) in progenitors expressing Ngn2 (neurogenin homolog). The lack of Otx2 also resulted in the activation of Pax3 (paired box gene), Pax7, and Lim1 (Lin-11/Isl-1/Mec-3), three genes normally coexpressed with Mash1 and GABAergic markers in the pretectum, thus suggesting that thalamic progenitors lacking Otx2 exhibit marker similarities with those of the pretectum. Furthermore, Otx2 ablation gave rise to a marked increase in proliferating activity of thalamic progenitors and the formation of hyperplastic cell masses. Thus, this study provides evidence for a novel and crucial role of Otx2 in the molecular mechanism by which identity and fate of glutamatergic precursors are established in the thalamus. Our data also support the concept that proper assignment of identity and fate of neuronal precursors occurs through the suppression of alternative differentiation programs.
A Combined Multiple‐Regression and Bioenergetics Model for Simulating Fish Growth in Length and Condition
Authors: Bajer Przemyslaw G. , Hayward Robert S.
Published: May 2006

We determined the relationships between the length relative growth rate (LRGR) and weight relative growth rate (WRGR) in white crappies Pomoxis annularis of various sizes (35–399 g) and condition factors (relative weight [Wr] range, 73–109) grown at varying rates via the manipulation of ration in eight 60‐d laboratory experiments. The WRGR alone explained 63% of the variation in LRGR. However, the slope (β1) of the LRGR–WRGR relationship varied with white crappie Wr and body weight; β1 increased exponentially with Wr and declined as a power function of weight. A multiple‐regression (MR) model that predicted LRGR from WRGR, Wr, and fish weight was constructed (R2 = 0.77; P < 0.0001) and combined with an existing white crappie bioenergetics model (BEM) that was originally capable of predicting growth in terms of weight only. Output from the BEM provided input to the MR model in each modeling time step. Independent evaluations showed that the combined BEM–MR model accurately predicted the observed trajectories of white crappie growth in length (±2.1%) and Wr (±4.1 units) from daily predictions of fish weight and length over 60‐d periods. The combined BEM–MR model was initiated with a fish's day‐1 observed weight, length, and Wr values and was run continuously (without resetting values) for full‐experiment durations by use of previous‐day outputs as inputs for next‐day predictions. The demonstrated capacity to adapt an existing BEM to accurately simulate a fish species' growth in length and change in condition, in addition to growth in weight, is expected to substantially expand the scope of application of BEMs in fisheries management and aquatic ecology.
Comparison of Adult Steelhead Migrations in the Mid‐Columbia Hydrosystem and in Large Naturally Flowing British Columbia Rivers
Authors: English K. K. , Robichaud D. , Sliwinski C. , Alexander R. F. , Koski W. R. , Nelson T. C. , Nass B. L. , Bickford S. A. , Hammond S. , Mosey T. R.
Published: May 2006

The migration of 1,263 adult radio‐tagged steelhead Oncorhynchus mykiss was assessed in the Nass, Skeena, Bella Coola, Fraser, and mid‐Columbia rivers from 1993 to 2001. Of the summer‐run steelhead tagged in the mid‐Columbia River, 80–87% eventually continued their upstream migration after being tagged, and 87–90% of those were detected in spawning areas. Similar results were seen for summer‐run steelhead tracked on the Nass and Skeena rivers. Mid‐Columbia summer‐run steelhead stocks that passed five dams en route to their spawning destinations (Methow and Okanogan rivers) traveled at a median rate of 20 km/d, which exceeded the median rates for summer‐run steelhead tracked on the Nass (3.8 km/d) and Skeena rivers (12–16 km/d). The upstream migration rates were best explained by river gradient and distance of the study area from the ocean. When the effects of river gradient and reach location were taken into account, impoundment was still a significant factor increasing the upstream migration speeds of summer‐run steelhead. Kelting speeds varied widely among rivers and did not appear to be a function of gradient.
Observer Error Structure in Bull Trout Redd Counts in Montana Streams: Implications for Inference on True Redd Numbers
Authors: Muhlfeld Clint C. , Taper Mark L. , Staples David F. , Shepard Bradley B.
Published: May 2006

Despite the widespread use of redd counts to monitor trends in salmonid populations, few studies have evaluated the uncertainties in observed counts. We assessed the variability in redd counts for migratory bull trout Salvelinus confluentus among experienced observers in Lion and Goat creeks, which are tributaries to the Swan River, Montana. We documented substantially lower observer variability in bull trout redd counts than did previous studies. Observer counts ranged from 78% to 107% of our best estimates of true redd numbers in Lion Creek and from 90% to 130% of our best estimates in Goat Creek. Observers made both errors of omission and errors of false identification, and we modeled this combination by use of a binomial probability of detection and a Poisson count distribution of false identifications. Redd detection probabilities were high (mean = 83%) and exhibited no significant variation among observers (SD = 8%). We applied this error structure to annual redd counts in the Swan River basin (1982–2004) to correct for observer error and thus derived more accurate estimates of redd numbers and associated confidence intervals. Our results indicate that bias in redd counts can be reduced if experienced observers are used to conduct annual redd counts. Future studies should assess both sources of observer error to increase the validity of using redd counts for inferring true redd numbers in different basins. This information will help fisheries biologists to more precisely monitor population trends, identify recovery and extinction thresholds for conservation and recovery programs, ascertain and predict how management actions influence distribution and abundance, and examine effects of recovery and restoration activities.
Early Cellular Responses in Cortical Bone Healing Around Unloaded Titanium Implants: An Animal Study
Authors: Slaets Elke , Carmeliet Geert , Naert Ignace , Duyck Joke
Published: May 2006

Background: A clear understanding of the early cellular events leading to osseointegration of implants is currently lacking. To gain better insight, titanium implants were inserted in a rabbit model and histologic and histomorphometric analyses were performed at early time points after insertion.

Methods: Thirty‐six cylindrical implants were inserted in the tibial diaphysis of six rabbits and left to heal for 1 to 42 days. Samples were processed into paraffin or methylmethacrylate sections, on which the surface of new bone, region of altered nuclear morphology, relative surface of basic multicellular units (BMUs) and blood vessels, and bone‐to‐implant contact were measured.

Results: After coagulum formation, osteoclasts and osteoblasts were observed at the bone surface 1 week after healing. In the preexisting bone, osteocytic lacunae appeared to be devoid of cells. This region of altered nuclear morphology continued to extend for 28 days (P <0.05) after implant insertion. This expansion was accompanied by an invasion of the damaged bone by BMUs that initiated intensive bone remodeling, which reached its maximum after 4 weeks (P <0.05) but was ongoing after 6 weeks of implant insertion.

Conclusions: This study evaluated the early cellular events in cortical bone surrounding titanium implants. The insertion of an implant into bone initiates a series of biologic processes, including the formation of a hematoma, altered nuclear morphology of the osteocytes surrounding the implantation site, intensive bone remodeling, and the formation of new bone, eventually leading to the osseointegration of the implant.