bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of Follicular Apoptosis in Water Buffalo (Bubalus bubalis) Ovary by Histology and Nick End Labelling Technique
Authors: Sreejalekshmi P , Raghavendra BS , Siva Subramani T , Chandrashekara Murthy V , Jamuna KV , Prasad RV , Ravindra JP , Selvaraju S
Published: January 2010

Contents

The objective of this experiment was to assess the features and extent of follicular apoptosis in the water buffalo (Bubalus bubalis) ovary using classical histology and nick end labelling technique. Ovaries (n = 40) procured from the slaughterhouse were used for the study. The sections (5 μm) were used for detection of terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labelling (TUNEL) and classical histology (H&E). Those follicles showing ≥ 5% TUNEL positivity (TUNEL assay) and pyknotic nuclei (histology) in granulosa cells were classified as atretic. Based on histology, the atretic primary and secondary follicles (%) were 93.82 and 95.62 respectively. The histology study reveals that the rates (%) of atresia in <1, 1–3, 3–5 mm and >5 mm were 36.90, 40.50, 62.84 and 74.5 respectively. Further the atretic tertiary follicles (%) were significantly lower than the primary and secondary classes of follicles. TUNEL assay reveals that the atretic rate (%) of tertiary follicles in <1, 1–3, 3–5 and ≥ 5 mm class follicles were 50.88, 53.84, 81.81 and 36.36 respectively. The percentage of atresia in >5 mm diameter follicles were significantly lower in TUNEL than histology. Percentages of granulosa and thecal cells positive for atresia by TUNEL were 30.7 ± 0.53 and 13.82 ± 0.18 respectively per follicle. The initial structural changes in atretic follicles were seen primarily in the granulosa cells. In severely atretic follicles TUNEL positive granulosa cells along with theca cells have to be considered in assessing the rate and extent of atresia.
Differential expression of peroxisome proliferator activated receptor γ and cyclin D1 does not affect proliferation of asthma‐ and non‐asthma‐derived airway smooth muscle cells
Authors: LAU Justine Y. , OLIVER Brian G. , MOIR Lyn M. , BLACK Judith L. , BURGESS Janette K.
Published: January 2010

Background and objective:  Airway remodelling involves thickening of the airway smooth muscle (ASM) bulk. Proliferation of asthma‐derived ASM cells is increased in vitro, but underlying mechanisms remain unknown. Peroxisome proliferators activated receptor‐γ (PPARγ) regulates the cell cycle. It is suggested that PPARγ agonists have anti‐inflammatory effects, which may be valuable in the treatment of asthma, but information regarding their antiproliferative properties in ASM is lacking. Although corticosteroids reduce airway inflammation, in vitro they inhibit proliferation in only non‐asthma ASM cells by reducing cyclin D1. We therefore investigated the effects of mitogenic stimulation (foetal bovine serum (FBS)), and a PPARγ ligand (ciglitazone), on PPARγ and cyclin D1 expression and proliferation of ASM cells. In addition, we examined the effects of ciglitazone on ASM cell proliferation.

Methods:  We assessed PPARγ and cyclin D1 mRNA and protein levels using quantitative PCR and immunoblotting. Cell proliferation was assessed using bromodeoxyuridine uptake.

Results:  In the presence of 5% FBS, PPARγ and cyclin D1 expression decreased over time in non‐asthmatic cells but increased in asthmatic cells (compared with sub‐confluent cells). FBS‐induced proliferation of asthmatic cells increased at all time points, but occurred only at day 7 with non‐asthmatic cells (compared with unstimulated time‐matched control). Ciglitazone increased PPARγ expression in both groups, but did not alter cell proliferation, while fluticasone increased PPARγ protein only in asthmatic cells.

Conclusions:  Although in the presence of a mitogenic stimulus, PPARγ was differentially expressed in asthma‐ and non‐asthma‐derived ASM; its expression was not related to the increased proliferation observed in asthmatic ASM.
Lower incidence of acute respiratory distress syndrome in community‐acquired pneumonia patients aged 85 years or older
Authors: TOBA Ayumi , YAMAZAKI Mariko , MOCHIZUKI Hideaki , NOGUCHI Toshiyuki , TSUDA Yasunari , KAWATE Eriko , SUZUKI Yohei , TAKAHASHI Hideki
Published: January 2010

Background and objective:  The incidence of and risk factors for ARDS among elderly patients with community‐acquired pneumonia (CAP) have not been well characterized.

Methods:  The clinical details of 221 consecutive patients aged ≥65 years, who were admitted with CAP during the period April 2006 to June 2008, were investigated by review of patient charts. Clinical variables and laboratory data at admission for CAP were compared between patients with and without ARDS.

Results:  Eighteen patients (8.1%) developed ARDS 1–5 days after admission. The mortality rate was 44% in patients with ARDS and 10.3% in those without ARDS (P < 0.001). The incidence of ARDS was 8.5–20% among patients aged <85 years and 1.1% in patients aged ≥85 years (P < 0.001), while overall mortality rates were not significantly different among the age groups. Predictors for the development of ARDS included higher serum levels of CRP and glucose, lower PaO2/fraction of inspired O2 (FiO2), PaCO2 and HCO3‐, and the presence of systemic inflammatory response syndrome at admission. ARDS developed less frequently among patients with pneumonia associated with oropharyngeal aspiration (AP). Multivariate analysis indicated that lower age, serum glucose, pre‐existence of systemic inflammatory response syndrome and non‐oropharyngeal AP were significant risk factors for ARDS. The Pneumonia Severity Index and confusion, urea, respiratory rate, blood pressure, age ≥65 score were not correlated with the incidence of ARDS.

Conclusions:  Predictors for ARDS appeared to differ from the determinants of severity of CAP in the elderly. ARDS developed less frequently in patients aged ≥85 years and in those with oropharyngeal AP. It is important to identify subjects at high risk for ARDS upon admission and to observe them closely.
Elevated serum CA‐125 levels in patients with non‐tuberculous mycobacterial lung disease
Authors: KIM Sun Young , HONG Yoonki , CHOI Chang‐Min , OH Yeon‐Mok , LEE Sang Do , KIM Woo Sung , KIM Dong Soon , SHIM Tae Sun
Published: January 2010

Background and objective:  Although cancer antigen 125 (CA‐125) is a useful marker for the diagnosis of ovarian cancer, CA‐125 levels are elevated in many benign conditions, including tuberculosis (TB). The clinical significance of serum CA‐125 measurements in patients with non‐tuberculous mycobacterial (NTM) lung disease was evaluated.

Methods:  Patients with NTM lung disease (n = 53), in whom serum CA‐125 levels had been measured, were retrospectively enrolled in the study. Twenty‐eight patients with pulmonary TB were included as a comparison group. Clinical, radiological and bacteriological parameters were assessed according to serum CA‐125 status.

Results:  Among 53 patients with NTM lung disease, serum CA‐125 levels were elevated in 28 (52.8%), and this proportion was not significantly different from that of the TB patients (44.8%). Cavitation and upper lobe cavitary type disease were more frequent in NTM patients with elevated serum CA‐125 levels compared with those without increased CA‐125 levels (P < 0.05 for both). The clinical course of NTM lung disease was correlated with changes in serum CA‐125 levels.

Conclusions:  Serum CA‐125 levels were increased in significant proportions of NTM patients, as well as TB patients. Further studies are needed to investigate the usefulness of serum CA‐125 measurements in patients with NTM pulmonary disease.
Prognostic factors in rapidly progressive interstitial pneumonia
Authors: KONDOH Yasuhiro , TANIGUCHI Hiroyuki , KATAOKA Kensuke , KATO Keisuke , SUZUKI Ryujiro , OGURA Takashi , JOHKOH Takeshi , YOKOI Toyoharu , WELLS Athol U. , KITAICHI Masanori
Published: January 2010

Background and objective:  The aim of the present study was to examine clinical and other features that might allow prognostic distinctions between histological patterns in presentations with rapidly progressive interstitial pneumonia (RPIP), and to assess prognostic factors for survival.

Methods:  Patients with RPIP among 425 consecutive patients with diffuse lung disease, who underwent surgical lung biopsy, were studied retrospectively. The discriminatory value of clinical and investigative features for identifying disease with a better outcome was evaluated. An a priori comparison was made between diffuse alveolar damage (DAD)/usual interstitial pneumonia with DAD pattern (Group A), and organizing pneumonia/non‐specific interstitial pneumonia pattern (Group B).

Results:  Twenty‐eight patients (6.6%) fulfilled the criteria for RPIP. The diagnosis was Group A disease in 15 (DAD in 10, usual interstitial pneumonia with DAD in 5), and Group B disease in 13 (organizing pneumonia in 8, non‐specific interstitial pneumonia in 5). There were no significant differences in initial findings between the groups. Prognosis was significantly better for Group B patients than for Group A patients (P = 0.021). Neither BAL nor parenchymal high‐resolution CT score was indicative of therapeutic responsiveness or outcome. Distinction between Group A and Group B on the basis of disease pattern was the only significant determinant of prognosis.

Conclusions:  RPIP included varied histological patterns with different outcomes, and in many cases these could not be predicted using baseline clinical data. Histology was the only significant predictor of ultimate prognosis.
Fire‐eater's lung complicated by an infectious abscess requiring surgical treatment
Authors: HARLANDER Matevž , TERČELJ Marjeta , SOK Mihael , ROTT Tomaž
Published: January 2010

We describe a case of fire‐eater's pneumonia that was complicated by an infectious lung abscess with substantial haemoptysis. Conservative treatment was inadequate. Surgical resection was necessary and proved to be successful.
A case report: Magnesium intoxication occurring in the process of total serum magnesium decrease
Authors: Tang Feige , Xiao Bing , Xiong Qing , Yang Ming
Published: January 2010

Magnesium intoxication is a result of excessively high serum magnesium levels, which are generally represented by a patient's total serum magnesium concentration. This is the first case report in PubMed in which a female patient showed no signs of magnesium intoxication when her total serum magnesium concentration was 4.34 mg/dL, but showed signs of magnesium intoxication (i.e. absent‐patellar reflex) when the concentration was 3.66 mg/dL. We concluded that the serum magnesium level cannot be represented by the total serum magnesium concentration to a full extent; a lower total serum magnesium concentration may still lead to magnesium intoxication.
Effect of single‐visit VIA and cryotherapy cervical cancer prevention program in Roi Et, Thailand: A preliminary report
Authors: Chumworathayi Bandit , Blumenthal Paul D. , Limpaphayom Khunying Kobchitt , Kamsa‐ard Supot , Wongsena Metee , Supaatakorn Pongsatorn
Published: January 2010

Aim:  To assess the effect of introducing visual inspection with acetic acid and cryotherapy on cervical cancer incidence rates in Roi Et province over time, between 1997 and 2006, and compare this with two nearby provinces.

Methods:  Data from two cancer registration units, one in Srinagarind Hospital and another in Ubon Ratchathani Cancer Center (to which all cervical cancer patients were referred from the three study provinces) were registered, extracted, combined and analyzed using a generalized estimation equation.

Results:  Cervical cancer detection rates improved. These are represented by the apparent increased incidence rates in Roi Et province during the study period compared with two nearby provinces (P = 0.01), equivalent to a doubling of the previously reported age‐standardized incidence ratio and three times its baseline in 2006.

Conclusions:  A single‐visit approach to cervical cancer prevention in Roi Et province using visual inspection with acetic acid and cryotherapy appeared to have an effect in revealing an increased cervical cancer incidence rate by achieving higher coverage, resulting in increased case finding.
Effects of glucocorticoid on brain acetylcholinesterase of developing chick embryos
Authors: Yamate Sumire , Nishigori Hidekazu , Kishimoto Seishi , Tezuka Yu , Fukushima Akimune , Sugiyama Toru , Nishigori Hideo
Published: January 2010

Aim:  Fetal exposure to excessive or deficient glucocorticoids may alter the programming in differentiation and maturation of various tissues including the brain and nervous system, leading to dysfunctions later in life. For further exploration of this possibility, we established an animal model using developing chick embryos.

Methods:  (i) Reverse‐transcription polymerase chain reaction was used to determine the expression of glucocorticoid receptor mRNA in the brain of chick embryos. (ii) Embryos on day 15 were administered betamethasone or mifepristone and their cerebrum, cerebellum and optic lobe were investigated to determine the activity of acetylcholinesterase.

Results:  (i) Glucocorticoid receptor mRNA was shown to be present in the cerebrum, cerebellum and optic lobe. (ii) After the administration of betamethasone, acetylcholinesterase activities in the cerebrum, cerebellum and optic lobe on day 19 were 1.5‐ to 2‐fold higher than those of untreated control. Weights of body and brain parts were 0.65–0.75‐fold relative to control values. However, these differences were less noticeable on day 22. (iii) Administration of mifepristone before treatment with betamethasone prevented high‐dose betamethasone‐induced changes in acetylcholinesterase activity and bodyweights on day 19. Administration of mifepristone alone did not induce differences from the control.

Conclusions:  The cerebrum, cerebellum and optic lobe of chick embryos could be influenced by glucocorticoids because of the presence of glucocorticoid receptor mRNA. Although the effects observed after treatment with excess glucocorticoids (even no effects after mifepristone treatment) were transitory, they may alter the developmental program in ways that could result in lasting change and influence behavioral activities after hatching.
A randomized controlled trial comparing short versus long‐term catheterization after uncomplicated vaginal prolapse surgery
Authors: Kamilya Gourisankar , Seal Subrata Lall , Mukherji Joydev , Bhattacharyya Subir Kumar , Hazra Avijit
Published: January 2010

Aims:  Routine catheterization following vaginal prolapse surgery has advantages like prevention of postoperative retention of urine and prevention of any adverse effect on surgical outcome. However, it increases the risk of urinary tract infection (UTI), prevent early ambulation and prolong hospital stay. This randomized controlled trial was done on how best to minimize catheter related complication after prolapse surgery.

Methods:  200 patients planned for vaginal prolapse surgery were recruited and randomized into two groups. In group I and group II catheter was removed on 1st and 4th post operative day, respectively. After removal, if patient could not void or when residual urine volume exceeds 150 mL, recatheterisation was done for another three days. Sample of urine was sent for culture during catheter removal.

Results:  Age, parity, type of surgery and mean operation time did not differ significantly between the two groups. Mean duration of catheterization was significantly shorter (1.64 vs 4.09) and mean duration of hospital stay was shorter by 1.2 days, in first group. However a significantly higher number of retention of urine or residual urine more than 150 mL was found in the early removal group (OR 3.10) but lesser chance of development of urinary tract infection (OR 0.10).

Conclusions:  The early removal of catheter seems more advantageous, with lower incidence of urinary tract infection and a shorter hospital stay although associated with an increased risk of recatheterisation.
A 1‐year maintenance after early adjuvant intravesical chemotherapy has a limited efficacy in preventing recurrence of intermediate risk non‐muscle‐invasive bladder cancer
Authors: Serretta Vincenzo , Morgia Giuseppe , Altieri Vincenzo , Di Lallo Alessandra , Ruggiero Giovanni , Salzano Luigi , Battaglia Michele , Falsaperla Mario , Zito Aniello , Sblendorio Domenico , Melloni Darvinio , Allegro Rosalinda ,   members of Gruppo Studi Tumori Urologici (GSTU) Foundation
Published: January 2010

Study Type – Therapy (RCT) Level of Evidence 1b

OBJECTIVE

To evaluate the efficacy of 1‐year maintenance after a 6‐week cycle of early intravesical chemotherapy, as the role of maintenance in intravesical chemotherapy is debated.

PATIENTS AND METHODS

Between May 2002 and August 2003, 577 patients with non‐muscle‐invasive bladder cancer (NMI‐BC) underwent transurethral resection (TUR) and early intravesical chemotherapy (epirubicin, 80 mg/50 mL). They were randomized between a 6‐week induction cycle and the induction cycle plus maintenance with 10 monthly instillations. In all, 95 patients with T1G3, Tis or single and primary Ta–T1 G1–G2 tumours were excluded; 482 patients at intermediate risk of recurrence continued the study. All patients had cytology and cystoscopy at 3‐monthly intervals for the first 2‐years and 6‐monthly thereafter.

RESULTS

The tumours’ characteristics were equally distributed between the two arms. Treatment interruption for toxicity was required in 39 patients. One death due to toxicity of early instillation occurred. The median follow‐up was 48 months. Ten patients (2.5%) progressed and 117 patients (29.6%) recurred. No statistically significant difference in the recurrence‐free rate (RFS) was detected between the two arms (P = 0.43). An advantage in favour of the maintenance arm was evident only at 18 months after TUR (P = 0.03). A trend for a higher benefit from maintenance in primary and multiple tumours was detected.

CONCLUSIONS

In patients with intermediate risk NMI‐BC treated by TUR and early adjuvant chemotherapy, adding a maintenance regimen with monthly instillations for 1 year is of limited efficacy in preventing recurrence.
Union Wage Effects in Australia: Evidence from Panel Data
Authors: Cai Lixin , Waddoups C. Jeffrey
Published: January 2010

Using data from the Household, Income and Labour Dynamics in Australia (HILDA) Survey, we find evidence that unobserved heterogeneity substantially biases cross‐sectional estimates of union wage effects upward for both male and female workers. The estimate of the union wage premium for male workers falls from 8.7 per cent to 5.2 per cent after controlling for unobserved heterogeneity. For females the estimated 4.0 per cent cross‐sectional union wage premium falls to 2.0 per cent once unobserved heterogeneity is controlled for. Among males, the results suggest negative sorting into union status at high levels of observed skill, while the sorting is positive at the lower end of the skill hierarchy. There is not sufficient evidence to support a similar pattern of sorting among female workers.
EPISTEMIC SELF‐INDULGENCE
Authors: BATTALY HEATHER
Published: January 2010

Abstract:I argue in this essay that there is an epistemic analogue of moral self‐indulgence.Section 1analyzes Aristotle's notion of moral temperance, and its corresponding vices of self‐indulgence and insensibility.Section 2uses Aristotle's notion of moral self‐indulgence as a model for epistemic self‐indulgence. I argue that one is epistemically self‐indulgent only if oneeither: (ESI1) desires, consumes, and enjoys appropriate and inappropriate epistemic objects; or (ESI2) desires, consumes, and enjoys epistemic objects at appropriate and inappropriate times; or (ESI3) desires and enjoys epistemic objects too frequently, or to an inappropriately high degree, or consumes too much of them. We need not look far to locate the epistemically self‐indulgent: philosophers, especially skeptics, are likely candidates.
AGENCY ASCRIPTIONS IN ETHICS AND EPISTEMOLOGY: OR, NAVIGATING INTERSECTIONS, NARROW AND BROAD
Authors: AXTELL GUY
Published: January 2010

Abstract:In this article, the logic and functions of character‐trait ascriptions in ethics and epistemology is compared, and two major problems, the “generality problem” for virtue epistemologies and the “global trait problem” for virtue ethics, are shown to be far more similar in structure than is commonly acknowledged. Beyond theaporiaof character‐trait ascription and between the Scylla and Charybdis that virtue theories are faced with in each field of philosophy, we find our passage by making full and explicit use of the “narrow‐broad spectrum of trait ascription,” and by accounting for the various uses of it in an inquiry‐pragmatist account. In virtue theories informed by inquiry pragmatism, the agential habits and abilities deemed salient in explanations/evaluations of agents in particular cases, and the determination of the relevant domains and conditions that an agent's habit or ability is reliably efficacious in, is determined by pragmatic concerns related to our evaluative epistemic practices.
OPEN‐MINDEDNESS
Authors: RIGGS WAYNE
Published: January 2010

Abstract: Open‐mindedness is typically at the top of any list of the intellectual or “epistemic” virtues. Yet, providing an account that simultaneously explains why open‐mindedness is an epistemically valuable trait to have and how such a trait is compatible with full‐blooded belief turns out to be a challenge. Building on the work of William Hare and Jonathan Adler, I defend a view of open‐mindedness that meets this challenge. On this view, open‐mindedness is primarily an attitude toward oneself as a believer, rather than toward any particular belief. To be open‐minded is to be aware of one's fallibility as a believer, and to acknowledge the possibility that anytime one believes something, one could be wrong. In order to see that such an attitude is epistemically valuable even to an already virtuous agent, some details of the skills and habits of the open‐minded agent are elucidated.
FEELING WITHOUT THINKING: LESSONS FROM THE ANCIENTS ON EMOTION AND VIRTUE‐ACQUISITION
Authors: COPLAN AMY
Published: January 2010

Abstract:By briefly sketching some important ancient accounts of the connections between psychology and moral education, I hope to illuminate the significance of the contemporary debate on the nature of emotion and to reveal its stakes. I begin the essay with a brief discussion of intellectualism in Socrates and the Stoics, and Plato's and Posidonius's respective attacks against it. Next, I examine the two current leading philosophical accounts of emotion: the cognitive theory and the noncognitive theory. I maintain that the noncognitive theory better explains human behavior and experience and has more empirical support than the cognitive theory. In the third section of the essay I argue that recent empirical research on emotional contagion and mirroring processes provides important new evidence for the noncognitive theory. In the final section, I draw some preliminary conclusions about moral education and the acquisition of virtue.
EXEMPLARIST VIRTUE THEORY
Authors: ZAGZEBSKI LINDA
Published: January 2010

Abstract:In this essay I outline a radical kind of virtue theory I call exemplarism, which is foundational in structure but which is grounded in exemplars of moral goodness, direct reference to which anchors all the moral concepts in the theory. I compare several different kinds of moral theory by the way they relate the concepts of the good, a right act, and a virtue. In the theory I propose, these concepts, along with the concepts of a duty and of a good life, are defined by reference to exemplars, identified directly through the emotion of admiration, not through a description. It is an advantage of the theory that what makes a good person good is not givena prioribut is determined by empirical investigation. The same point applies to what good persons do and what states of affairs they aim at. The theory gives an important place to empirical investigation and narratives about exemplars analogous to the scientific investigation of natural kinds in the theory of direct reference.
A CHALLENGE TO INTELLECTUAL VIRTUE FROM MORAL VIRTUE: THE CASE OF UNIVERSAL LOVE
Authors: SWANTON CHRISTINE
Published: January 2010

Abstract: On the Aristotelian picture of virtue, moral virtue has at its core intellectual virtue. An interesting challenge for this orthodoxy is provided by the case of universal love and its associated virtues, such as the dispositions to exhibit grace, or to forgive, where appropriate. It is difficult to find a property in the object of such love, in virtue of which grace, for example, ought to be bestowed. Perhaps, then, love in general, including universal love, is not necessarily exhibited for reasons. This is the view that, with the help of Heidegger's notion of a fundamental emotional attunement (Grundstimmung), I defend. The problem is to show how universal love, and its manifestation in the virtues of universal love, can then be seen as rational. Showing this is the task of the essay.
INTRODUCTION: VIRTUE AND VICE
Authors: BATTALY HEATHER
Published: January 2010

Abstract:This introduction to the collectionVirtue and Vice, Moral and Epistemicaddresses three main questions: (1) What is a virtue theory in ethics or epistemology? (2) What is a virtue? and (3) What is a vice? (1) It suggests that a virtue theory takes the virtues and vices of agents to be more fundamental than evaluations of acts or beliefs, and defines right acts or justified beliefs in terms of the virtues. (2) It argues that there are two important but different concepts of virtue: virtues are qualities that attain good ends, and virtues are qualities that involve good motives. (3) Accordingly, vices are qualities that either fail to attain good ends or involve bad motives. Finally, the introduction summarizes the eleven essays in the collection, which are divided into four sections: the Structure of Virtue Ethics and Virtue Epistemology; Virtue and Context; Virtue and Emotion; and Virtues and Vices.
Mid‐dosing interval concentration of atazanavir and virological outcome in patients treated for HIV‐1 infection
Authors: Fabbiani M , Di Giambenedetto S , Ragazzoni E , Colafigli M , Prosperi M , Cauda R , Navarra P , De Luca A
Published: January 2010

Objectives

We investigated the clinical significance of monitoring the mid‐dosing interval atazanavir (ATV) concentration (measured 12 ± 2 h after intake; C12 h) in patients taking this drug once daily in the evening.

Methods

We retrospectively selected HIV‐infected patients harbouring ATV‐susceptible virus who underwent therapeutic drug monitoring (TDM) of ATV C12 h during routine out‐patient visits, and we correlated C12 h to the 24‐week virological response and toxicity.

Results

A total of 115 plasma samples from 86 patients (76.7% with baseline HIV RNA<50 HIV‐1 RNA copies/mL) were analysed. ATV plasma concentrations showed high inter‐individual variability. ATV plasma levels were higher in samples obtained from patients taking boosted regimens (P<0.001) and not concomitantly receiving acid‐reducing agents (P=0.007). In a multivariate model, ritonavir boosting, use of acid‐reducing agents and liver cirrhosis showed an independent association with ATV level. Virological response at 24 weeks was observed for 94 of the 115 samples (81.7%). We identified a concentration cut‐off of 0.23 mg/L which predicted virological response at 24 weeks: samples with a C12 h≤0.23 mg/L showed virological failure in 41.2% of cases, whereas samples with a C12 h>0.23 mg/L showed virological failure in 14.3% of cases (P=0.021). In multivariate analysis, C12 h>0.23 mg/L was an independent predictor of virological response [odds ratio (OR) 4.23, P=0.031]. ATV levels correlated with concomitant unconjugated bilirubin levels (r=0.223, P=0.037), but a concentration cut‐off predictive of moderate/severe hyperbilirubinaemia could not be identified.

Conclusions

We identified a C12 h efficacy threshold that predicted virological response; this could be useful for morning TDM in selected subjects receiving ATV in the evening. Results must be interpreted with caution given the retrospective design of the study.
Introduction of pharmacogenetic screening for the human leucocyte antigen (HLA) B*5701 variant in Polish HIV‐infected patients
Authors: Parczewski M , Leszczyszyn‐Pynka M , Wnuk A , Urbañska A , Fuksiñska K , Bander D , Boroñ‐Kaczmarska A
Published: January 2010

Objective

Prospective pharmacogenetic screening for the human leucocyte antigen (HLA) B*5701 allele can significantly reduce the number of cases of abacavir‐related hypersensitivity among HIV‐infected patients treated with this drug. The aim of this study was to establish the frequency of the HLA B*5701 variant in HIV‐infected Poles.

Methods

The sequence‐specific primer (SSP) test was used to assess the feasibility of the introduction of such testing in clinical practice. For this purpose, 234 randomly selected HIV‐positive patients were screened using a low‐resolution SSP assay, with HLA B*5701‐positive results confirmed using a high‐resolution test.

Results and Conclusions

The HLA B*5701 variant was found in 11 of 234 subjects (4.7%). Testing with the selected method proved quick and reliable.
Search for Mitochondrial Dna Mutations in Migraine Subgroups
Authors: Haan J , Terwindt GM , Maassen JA , Hart LM , Frants RR , Ferrari MD
Published: January 2010

It has been suggested that mitochondrial mutations cause migraine(-like) symptoms. The presence of mtDNA mutations (3243, 3271, 11084, and deletions) was investigated in three migraine subgroups (maternally transmitted migraine with and without aura, migrainous infarction, and nonfamilial hemiplegic migraine). No mutations were found. These mutations and deletions probably are not involved in the migraine subgroups studied, although an investigation of other material (e.g., muscle tissue) would have shown this with more certainty.
Steady-State Visual-Evoked Potentials in Headache: Diagnostic Value in Migraine and Tension-Type Headache Patients
Authors: de Tommaso M , Sciruicchio V , Guido M , Sasanelli G , Puca F
Published: January 2010

We tested the hypothesis that migraine and tension-type headache are separate disorders based on visual evoked potentials. We recruited 120 migraine without aura patients (MwoA), 64 tension-type headache patients (TTH), and 51 healthy controls. We performed discriminant analysis combined with a stepwise selection of predictors. Mean values of the F1 component were significantly increased over Fp1, C3, P4, O2 and O1 electrodes in MwoA and TTH patients compared with normal subjects. Only the control subjects were correctly distinguished. The increased brain response to visual stimulation detected in both MwoA and TTH may suggest a common neuronal dysfunction in the two headache subtypes.
Lamotrigine in the Prophylactic Treatment of Migraine Aura— A Pilot Study
Authors: Lampl C , Buzath A , Klinger D , Neumann K
Published: January 2010

The aim of this study was to evaluate the efficacy of lamotrigine, a glutamate antagonist blocking voltage-sensitive sodium channels, in the prophylaxis of migraine aura symptoms. Glutamate is one of the main neurotransmitters involved in the development of cortical spreading depression. The study was conducted as an open longitudinal trial over 7 months, with a treatment phase of 4 months and a post-treatment period of 3 months. Thirteen patients suffering from migraine with aura and 2 patients with aura but without migraine were enrolled and treated with lamotrigine. The dose was gradually increased in steps of 25 mg up to 100 mg per day, depending on the patient's aura symptoms. Aura symptoms were reduced from baseline (an average of 1.3 aura episodes per month) to month 4 (0.1, p< 0.001). High statistical significance was also observed with regard to aura duration (23 min at baseline vs 4 min at 4 months, p< 0.001). In all 15 cases, increases in aura frequency (on average sevenfold, p< 0.001) and aura duration (minutes; on average more than threefold, p< 0.001) were evident following cessation of treatment. A number of mild to moderate adverse events without any medical consequences occurred. The study outcome suggests that lamotrigine is effective in preventing migraine aura symptoms and in influencing migraine headache frequency.
Olfactory and Trigeminal Event-Related Potentials in Migraine
Authors: Grosser K , Oelkers R , Hummel T , Geisslinger G , Brune K , Kobal G , Lötsch J
Published: January 2010

Background: Trigeminal/neuronal hyperexcitability and spreading depression activating the trigemino-vascular system are discussed in migraine-pathophysiology. This study investigated trigeminal and olfactory event-related potentials in migraineurs. Methods: Nasal chemosensitivity was assessed in 19 female migraineurs with or without aura > 72 h before or after an attack and in 19 healthy females employing event-related cortical potentials (ERPs) after specific trigeminal stimulation of nasal nociceptors with short pulses of CO2, and specific olfactory stimulation with H2S. Odour thresholds and odour identification performance were also tested. Results: Migraineurs exhibited greater responses to trigeminal stimulation, indicated by significantly larger ERP amplitudes N1. In contrast, olfactory ERP amplitudes P1N1 were significantly smaller in migraineurs. A leave-one-out classification procedure on the basis of these two parameters assigned 76.3% cases correctly. The olfactory ERP amplitude discriminated better between groups than trigeminal ERPs (71.1 vs. 68.4% correct classification). Conclusions: Our data suggest trigeminal hyperexcitability in migraineurs. A general increase of nasal chemosensitivity is not supported because of smaller olfactory ERP amplitudes in migraineurs. Olfactory ERPs discriminate better than trigeminal ERPs between migraineurs and controls, emphasizing the significance of the olfactory system in migraine.
Asymmetrical Reduction of the Nociceptive Flexion Reflex Threshold in Cluster Headache
Authors: Sandrini G , Antonaci F , Lanfranchi S , Milanov I , Danilov A , Nappi G
Published: January 2010

The nociceptive flexion reflex (NFR) of the lower limbs (RIII reflex) was examined bilaterally in 54 cluster headache (CH) patients suffering from episodic CH (ECH) and chronic CH (CCH). Fifteen ECH patients were examined in both remission and active phases. The RIII reflex threshold (Tr) and the threshold of pain sensation (Tp) were significantly reduced on the symptomatic side in patients with episodic CH during the bout. During the active phase of episodic CH an inverse correlation was found between the severity of CH (ratio: number of cluster periods/years of illness duration) and the Tp, which may suggest a role for secondary central sensitization in pain pathways. The lower Tr and Tp on the symptomatic side is in keeping with previous observations exploring pain mechanisms using different methods (i.e. corneal reflex, pain pressure threshold). On the whole, these data tie in with the view of an impairment of the pain control system, which parallels the periodicity of the disorder in the episodic form.
Acetylsalicylic Acid Effervescent 1000 mg (Aspirin®) in Acute Migraine Attacks; A Multicentre, Randomized, Double-Blind, Single-Dose, Placebo-Controlled Parallel Group Study
Authors: Lange R , Schwarz JA , Hohn M
Published: January 2010

In this multicentre, randomized, double-blind, single-dose study a total of 374 patients generally suffering from migraine attacks suitable for treatment with non-prescription drugs, received either oral acetylsalicylic acid effervescent 1000 mg (ASAE) or effervescent placebo for the treatment of an acute migraine attack. Of the 343 patients fulfilling the criteria for efficacy analysis 169 patients took acetylsalicylic acid and 174 placebo. Response rates (reduction of headache severity from severe or moderate to mild or no pain at 2 h after administration) were 55.0% for acetylsalicylic acid and 36.8% for placebo ( P < 0.001). Twenty-nine percent of patients in the active treatment group were pain-free after 2 h compared with 16.7% in the placebo group ( P = 0.007). No headache recurred within 24 h post-dose in 84.6% of patients in the active group and in 85.1% of patients in the placebo group. Effervescent placebo reduced nausea and vomiting to the same degree as the active drug. Adverse events of acetylsalicylic acid (8.3%) were generally mild or moderate and comparable to those of placebo (2.9%). This study shows that oral ASAE is safe and effective for the treatment of acute migraine attacks.
A Follow-Up Study of 60 Patients After an Assumed First Period of Cluster Headache
Authors: Sjöstrand C , Waldenlind E , Ekbom K
Published: January 2010

During 1981–96 a series of 60 consecutive out-patients was examined in relation to an assumed first period of cluster headache (CH). On follow up in 1998 we found that six were deceased at a mean age of 56.5 years (range 45–74 years), of whom one had a definitive CH diagnosis and five had one documented headache period only. Six patients were lost to follow up because they could not be reached. In the final group for evaluation ( n = 49) it was found that 13 (26.5%) patients had had one cluster period only during a mean observation time of 8.9 years. Out of 36 patients with a definitive CH diagnosis according to International Headache Society (IHS) criteria, 31 patients had episodic CH, four patients had primary chronic CH and one patient had secondary chronic CH. Of the patients with a definitive CH diagnosis, 83% on follow up had had a recurrence of a second period of CH within 3 years or continuous attacks (chronic/semichronic CH) from the onset. Evidently some patients may suffer from one cluster period only. In our patient material only 17% had a second cluster period after 3 years.
Distribution of Intranasal 11C-Zolmitriptan assessed by Positron Emission Tomography
Authors: Yates R , Sörensen J , Bergström M , Antoni G , Nairn K , Kemp J , Långström B , Dane A
Published: January 2010

Nine healthy volunteers aged 18-28 years were recruited into this open, single-centre, two-phase trial. In phase 1, two volunteers received a single dose of 11C-zolmitriptan 2.5 mg administered as a nasal spray and then underwent positron emission tomography (PET) scanning to determine the most appropriate times for scanning in phase 2. In phase 2, six volunteers received two doses and an additional volunteer one dose of 11C-zolmitriptan 2.5 mg intranasally. Volunteers underwent PET scanning over sectors covering one of the nasopharynx, lungs or abdomen, for up to 1.5 h postdose. The brain was also scanned and plasma zolmitriptan levels were measured. Almost 100% of the administered dose was detected in the nasopharynx immediately after dosing. This declined thereafter to about 50% at 20 min and to 35% at 80 min after dosing. Radioactivity appeared slowly in the upper abdomen, with 25% of given radioactivity detected at 20 min and persisting until 80 min after dosing. Minimal radioactivity was detected in the lungs. Radioactivity was detectable within brain tissue suggesting central penetration of zolmitriptan. Zolmitriptan in plasma had approached its maximum concentration by 15 min postdose. The data indicate initial absorption across the nasal mucosa contributing to an early systemic availability. 11C-Zolmitriptan administered intranasally was well tolerated.
The 3p21.1-p21.3 Hereditary Vascular Retinopathy Locus Increases the Risk for Raynaud's Phenomenon and Migraine
Authors: Hottenga JJ , Vanmolkot KRJ , Kors EE , Kheradmand Kia S , de Jong PTVM , Haan J , Terwindt GM , Frants RR , Ferrari MD , van den Maagdenberg AMJM
Published: January 2010

Previously, we described a large Dutch family with hereditary vascular retinopathy (HVR), Raynaud's phenomenon and migraine. A locus for HVR was mapped on chromosome 3p21.1-p21.3, but the gene has not yet been identified. The fact that all three disorders share a vascular aetiology prompted us to study whether the HVR haplotype also contributed to Raynaud's phenomenon and migraine in this family. Whereas the parent-child transmission disequilibrium test (TDT) did not reach significance, the sibling TDT revealed that the HVR haplotype harbours a susceptibility factor for Raynaud's phenomenon and migraine. Identification of the HVR gene will improve the understanding of the pathophysiology of HVR, Raynaud's phenomenon and migraine.
Perception of shapes targeting local and global processes in autism spectrum disorders
Authors: Grinter Emma J. , Maybery Murray T. , Pellicano Elizabeth , Badcock Johanna C. , Badcock David R.
Published: January 2010

Background:  Several researchers have found evidence for impaired global processing in the dorsal visual stream in individuals with autism spectrum disorders (ASDs). However, support for a similar pattern of visual processing in the ventral visual stream is less consistent. Critical to resolving the inconsistency is the assessment of local and global form processing ability.

Methods:  Within the visual domain, radial frequency (RF) patterns – shapes formed by sinusoidally varying the radius of a circle to add ‘bumps’ of a certain number to a circle – can be used to examine local and global form perception. Typically developing children and children with an ASD discriminated between circles and RF patterns that are processed either locally (RF24) or globally (RF3).

Results:  Children with an ASD required greater shape deformation to identify RF3 shapes compared to typically developing children, consistent with difficulty in global processing in the ventral stream. No group difference was observed for RF24 shapes, suggesting intact local ventral‐stream processing.

Conclusions:  These outcomes support the position that a deficit in global visual processing is present in ASDs, consistent with the notion of Weak Central Coherence.
Building a Regionally Connected Reserve Network in a Changing and Uncertain World
Authors: SPRING DANIEL , BAUM JIRI , NALLY RALPH MAC , MACKENZIE MICHAEL , SANCHEZ‐AZOFEIFA A. , THOMSON JAMES R.
Published: January 2010

Abstract:  Habitat connectivity is required at large spatial scales to facilitate movement of biota in response to climatic changes and to maintain viable populations of wide‐ranging species. Nevertheless, it may require decades to acquire habitat linkages at such scales, and areas that could provide linkages are often developed before they can be reserved. Reserve scheduling methods usually consider only current threats, but threats change over time as development spreads and reaches presently secure areas. We investigated the importance of considering future threats when implementing projects to maintain habitat connectivity at a regional scale. To do so, we compared forward‐looking scheduling strategies with strategies that consider only current threats. The strategies were applied to a Costa Rican case study, where many reserves face imminent isolation and other reserves will probably become isolated in the more distant future. We evaluated strategies in terms of two landscape‐scale connectivity metrics, a pure connectivity metric and a metric of connected habitat diversity. Those strategies that considered only current threats were unreliable because they often failed to complete planned habitat linkage projects. The most reliable and effective strategies considered the future spread of development and its impact on the likelihood of completing planned habitat linkage projects. Our analyses highlight the critical need to consider future threats when building connected reserve networks over time.
Effectiveness of Predator Removal for Enhancing Bird Populations
Authors: SMITH REBECCA K. , PULLIN ANDREW S. , STEWART GAVIN B. , SUTHERLAND WILLIAM J.
Published: January 2010

Abstract:  Predation pressure on vulnerable bird species has made predator control an important issue for international nature conservation. Predator removal by culling or translocation is controversial, expensive, and time‐consuming, and results are often temporary. Thus, it is important to assess its effectiveness from all available evidence. We used explicit systematic review methodology to determine the impact of predator removal on four measurable responses in birds: breeding performance (hatching success and fledging success) and population size (breeding and postbreeding). We used meta‐analysis to summarize results from 83 predator removal studies from six continents. We also investigated whether characteristics of the prey, predator species, location, and study methodology explained heterogeneity in effect sizes. Removing predators increased hatching success, fledging success, and breeding populations. Removing all predator species achieved a significantly larger increase in breeding population than removing only a subset. Postbreeding population size was not improved on islands, or overall, but did increase on mainlands. Heterogeneity in effect sizes for the four population parameters was not explained by whether predators were native or introduced; prey were declining, migratory, or game species; or by the study methodology. Effect sizes for fledging success were smaller for ground‐nesting birds than those that nest elsewhere, but the difference was not significant. We conclude that current evidence indicates that predator removal is an effective strategy for the conservation of vulnerable bird populations. Nevertheless, the ethical and practical problems associated with predator removal may lead managers to favor alternative, nonlethal solutions. Research is needed to provide and synthesize data to determine whether these are effective management practices for future policies on bird conservation.
Use of Land Facets to Plan for Climate Change: Conserving the Arenas, Not the Actors
Authors: BEIER PAUL , BROST BRIAN
Published: January 2010

Abstract:  Even under the most optimistic scenarios, during the next century human‐caused climate change will threaten many wild populations and species. The most useful conservation response is to enlarge and link protected areas to support range shifts by plants and animals. To prioritize land for reserves and linkages, some scientists attempt to chain together four highly uncertain models (emission scenarios, global air–ocean circulation, regional circulation, and biotic response). This approach has high risk of error propagation and compounding and produces outputs at a coarser scale than conservation decisions. Instead, we advocate identifying land facets—recurring landscape units with uniform topographic and soil attributes—and designing reserves and linkages for diversity and interspersion of these units. This coarse‐filter approach would conserve the arenas of biological activity, rather than the temporary occupants of those arenas. Integrative, context‐sensitive variables, such as insolation and topographic wetness, are useful for defining land facets. Classification procedures such as k‐means or fuzzy clustering are a good way to define land facets because they can analyze millions of pixels and are insensitive to case order. In regions lacking useful soil maps, river systems or riparian plants can indicate important facets. Conservation planners should set higher representation targets for rare and distinctive facets. High interspersion of land facets can promote ecological processes, evolutionary interaction, and range shift. Relevant studies suggest land‐facet diversity is a good surrogate for today's biodiversity, but fails to conserve some species. To minimize such failures, a reserve design based on land facets should complement, rather than replace, other approaches. Designs based on land facets are not biased toward data‐rich areas and can be applied where no maps of land cover exist.