bluuebunny/crossref_metadata_2025 huggingface dataset:
Rising Prevalence of Migraine in Taiwanese Adolescents Aged 13-15 Years
Authors: Wang S-J , Fuh J-L , Juang K-D , Lu S-R
Published: May 2005

Whether the prevalence of migraine is increasing is controversial. We conducted annual surveys in 1999-2001 to investigate migraine prevalence among a nationwide sample of 13 426 adolescents aged 13-15 years. Participants from five junior high schools around different regions of Taiwan completed self-administered questionnaires. The diagnosis of migraine was based on the classification criteria proposed by the International Headache Society, 1988. Data for 23 433 person-years were collected and analysed for trends in prevalence and incidence. The 1-year prevalence of migraine increased 42% during 1999-2001 (from 5.2 to 7.4%, P < 0.001). This increasing trend was demonstrated in both sexes, all ages, and all but one studied regions of Taiwan. Of note was the biggest increment of prevalence (79%) among 7th graders (students aged 13 years) through these 3 years. Annual incidence rates did not differ between 1999 and 2000 and 2000 and 2001 (6.1% vs. 5.7%; P = 0.4). One-year persistence rates of migraine diagnosis, surrogates of migraine duration, did not differ between 1999 and 2000 and 2000 and 2001 (34.2% vs. 41.2%; P = 0.1). Our study found that the prevalence of migraine was increasing in our sampled adolescents, which results from an increment starting at age 13 or younger. The prevalence of migraine in Asians might be increasing, although previous studies showed lower prevalence in this region. Children or adolescents may be more vulnerable to the environmental or societal change.
Familial SUNCT
Authors: Gantenbein AR , Goadsby PJ
Published: May 2005

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a rare type of primary headache. In this report we describe the occurrence of SUNCT in a family. Unfortunately, one of the siblings was already dead. However, clear and detailed information from close relatives and her general practitioner confirmed the diagnosis of SUNCT. It is likely that genetic factors contribute to all types of trigeminal autonomic cephalalgias.
Health, Equity and Intellectual Disability
Authors: Leeder Stephen R. , Dominello Amanda
Published: May 2005

In this paper, we first describe the current state of health across the world. We then note that despite general good health, it is not everyone's experience and that differences in health among people frequently appear to be unfair. Health promotion is a movement committed to prevention and to creating opportunities for all people to live healthy lives. We examine the application of health promotion to people with intellectual disability. Finally, we bring equity, health promotion and intellectual disability together and ask to what extent people with these problems are victims of inequity. If they are – as seems likely – societies that have built their health services on humane values should assume greater responsibility for meeting their special needs, promoting their opportunities for health as well as managing their illnesses.
Intellectual Disabilities and Socioeconomic Inequalities in Health: An Overview of Research
Authors: Graham Hilary
Published: May 2005

Background There is an enduring association between socioeconomic position and health, both over time and across major causes of death. Children and adults with intellectual disabilities are disproportionately represented among the poorer and less healthy sections of the population. But research on health inequalities, and on the broader societal influences on health, has yet to be integrated into perspectives and policy for people with intellectual disabilities.

Methods The paper reviews evidence on the patterns and causes of socioeconomic inequalities in health.

Results It points to evidence that socioeconomic position is the fundamental determinant of health, drawing on longitudinal studies to highlight how it exerts its influence on health from before birth and across the lifecourse. The factors shaping an individual's socioeconomic position are also discussed.

Conclusions The paper concludes by identifying research and policy challenges.
A Pilot of a Gerontological Advanced Practice Nurse Preventive Intervention
Authors: Hahn Joan Earle , Aronow Harriet Udin
Published: May 2005

Background  Persons with an intellectual and developmental disability frequently face barriers in accessing preventive services in community‐based health care systems. As they age into middle years, they are at increased risk for functional decline. This paper presents a description of an advanced practice nurse (APN) intervention used in a pilot study that explored the feasibility of using an in‐home preventive model based on a comprehensive geriatric assessment with persons ageing with an intellectual and developmental disability.

Method  The APN intervention was fully provided to a sub‐sample (n = 70) of 201 participants with an intellectual and developmental disability enrolled in a programme called ‘Stay Well and Healthy!’ The APN intervention included an initial home visit for a comprehensive geriatric assessment with follow‐up home visits to review health status and assess adherence with recommendations and provide education and support to promote health and prevent functional decline.

Results  Advanced practice nurses identified a number of active health‐related problems for persons ageing with an intellectual and developmental disability (mean 5.2; range 1–14) that had potential effects on function and survival. The majority of recommendations (mean 14.4; range 6–35) were for clinical preventive services (42.2%) and self‐care for health‐related issues (36.8%).

Conclusions  This study showed that there were problems consistent with persons ageing with an intellectual and developmental disability and older adults without disability. The in‐home preventive APN intervention to promote healthy ageing and reduce health disparities in this population is feasible, needed, and warrants further study.
The Development of a Health Status Measure for Self‐report by People with Intellectual Disabilities
Authors: Ruddick Loraine , Oliver Chris
Published: May 2005

Background  Health status is an important domain of quality of life of people with intellectual disabilities. This paper describes the development of a self‐report health status measure for use with people with intellectual disabilities living in staffed community‐based accommodation, and reports preliminary reliability data for the schedule.

Method  Question and response items were adapted from a well‐established measure (SF‐36) used in the general population incorporating subscales such as General Health, Physical Functioning, Bodily Pain, Vitality, Mental Health, and Sensory Functioning. A variety of closed and open response formats were used based on the growing literature examining methods for interviewing people with intellectual disabilities.

Results  Internal reliability and response consistency were investigated. Reliability for Physical Functioning, General Health and Bodily Pain was reasonable, but was unsatisfactory for Sensory Functioning, and Mental Health.

Conclusions  The findings are discussed in light of the challenge of eliciting reliable responses from people with intellectual disabilities. Question methodologies can be built upon in further research.
From Institutional to Community Support: Consequences for Medical Care
Authors: van Loon Jos , Knibbe Jeroen , Van Hove Geert
Published: May 2005

Background  Concerns have been raised about the quality of medical care available for people with intellectual disabilities in community‐based services. The aims of this study were to evaluate a model of medical care developed during a programme of deinstitutionalization, based on a specialist physician supporting general practitioners (GPs).

Method  Postal questionnaire survey of all 36 GPs participating in the specialist physician support programme. Responses were received from 22 participants (response rate 61%).

Results  The majority of GPs agreed that clients with intellectual disabilities should receive services in primary care settings. While they also reported themselves to be capable of providing medical care to people with intellectual disabilities, they also reported the provision of specialist support to be important.

Conclusions  It is possible to provide high quality medical care in community‐based settings if specialist support is made available for GPs.
Hospital Utilization among Persons with an Intellectual Disability, Ontario, Canada, 1995–2001
Authors: Balogh Robert S. , Hunter Duncan , Ouellette‐Kuntz Hélène
Published: May 2005

Background  It has been suggested that persons with an intellectual disability consume a disproportionate amount of hospital services. Policy changes in Ontario in the 1970s and 1980s made it necessary for community health services to accommodate this population that formerly received most of its medical care in the institutions where they lived. It is frequently suggested that community health services are currently inadequate to care for this population.

Methods  The study was a retrospective analysis of routinely collected hospitalization data for persons living in Ontario with an intellectual disability, between 1995 and 2001.

Results  A substantial proportion of hospitalizations of persons with an intellectual disability were for mental disorders and dental diseases. Of all in‐hospital stays, one‐third were for mental disorders such as schizophrenia and depression. Of all day‐surgery admissions, almost 40% were for dental diseases corresponding to a high rate of dental procedures. The study also identified high ambulatory care‐sensitive condition hospitalization rates. In‐hospital surgical procedure rates, however, were low.

Interpretation  This study is the first to fully describe patterns of hospitalization for persons with an intellectual disability in Ontario, Canada. A recurring finding is the large discrepancy between statistics for persons with an intellectual disability and published data for the general population. The study limitations mean further research is required to confirm the results and to determine if persons with an intellectual disability are receiving the health care they are entitled to in Ontario.
Abstract no.: 1  The vasorelaxing influence of adrenomedullin in isolated bovine retinal arteries
Authors: Boussery Koen , Delaey Christophe , Van de Voorde Johan
Published: May 2005

Aims:  Adrenomedullin (AM), a peptide noted in a broad variety of tissues and cells, is known to induce relaxations in different vascular beds and isolated blood vessels, including the (extra‐ocular) central retinal artery. A role for AM in the regulation of ocular blood flow has been suggested, but so far no data were available on the direct influence of AM on smooth muscle tone in intra‐ocular retinal arteries. The present study therefore aimed to assess and to characterise the vasorelaxing effect of AM on isolated (intra‐ocular) bovine retinal arteries (BRA).

Methods:  Retinal arteries were isolated from bovine eyes and mounted in a wire‐myograph for isometric tension recording. Concentration‐response curves were constructed by cumulative addition of AM (1 pM to 0.1 μM) in the organ bath.

Results:  AM caused a concentration‐dependent relaxation of the BRA. The AM‐response was reduced after removal of the endothelium of the BRA (30 nM: from 38.14 ± 4.90% to 25.71 ± 4.32% relaxation, n = 7, P < 0.05). Also treatment of the BRA with the NOS‐inhibitor L‐NA or the soluble guanylyl cyclase inhibitor ODQ significantly reduced the AM‐response, whereas cyclo‐oxygenase inhibition or the adenosine receptor antagonist 8‐SPT had no effect. The AM‐receptor antagonist AM 22–52 caused a small, but significant reduction in the AM‐response (30 nM: from 55.33 ± 9.65% to 47.50 ± 8.26% relaxation, n = 6, P < 0.05). The CGRP‐receptor antagonist CGRP 8–37 caused a more pronounced decrease in AM‐response (30 nM: from 55.43 ± 10.53% to 17.77 ± 6.57% relaxation, n = 6, P < 0.05).

Conclusion:  The present study demonstrates that AM induces vasodilation in isolated BRA. Thereby, our findings support the hypothesis that AM may have a role in the regulation of retinal blood flow. Endothelium‐derived NO and stimulation of CGRP‐ and AM‐receptors appear to be involved in the AM‐response, whereas prostanoids and activation of adenosine receptors are not involved.
Abstract no.: 3  Impaired clearance of apoptotic cells in atherosclerosis
Authors: Schrijvers Dorien M. , Martinet Wim , De Meyer Guido R.Y. , Kockx Mark M. , Herman Arnold G.
Published: May 2005

Background:  Apoptotic cell death is a prominent feature of human atherosclerotic plaques. When the apoptotic remains of a cell are not efficiently removed, inevitable leaking of the cell content occurs, inciting an inflammatory reaction. Since human atherosclerotic plaques show signs of both apoptosis and inflammation, we questioned whether cells induced to undergo apoptotic cell death are efficiently removed.

Results:  We compared the scavenging activity of macrophages in human carotid endarterectomy specimens with macrophages in human hyperplastic tonsils. The ratio of free versus phagocytized apoptotic cells was 19 times higher in the plaque, indicating a severe defect in clearance of apoptotic cells. To determine possible causes, fluorescently labelled apoptotic cells, were incubated with J774 macrophages or murine peritoneal macrophages under different atherosclerosis‐related conditions and phagocytosis was evaluated by flow cytometry. We found that overload of macrophages with inert particles (beads) prevented further uptake of apoptotic cells. Oxidative stress, induced by peroxynitrite donor SIN‐1A, significantly inhibited uptake of apoptotic cells as well. Oxidized erythrocytes (oxRBC) and oxidized low density lipoproteins (oxLDL) reduced phagocytosis of apoptotic cells by competition for the same receptor(s) on macrophages. Uptake of blood platelets did not affect phagocytosis of apoptotic cells.

Conclusion:  Our results demonstrate that clearance of apoptotic cells is deficient in human atherosclerosis, due to overfilling of macrophages, oxidative stress and competitive inhibition by oxLDL and oxRBC. This lack of clearance could have severe consequences regarding further accumulation of necrotic debris, plaque thrombogenicity and stability of human atherosclerotic plaques.
Abstract no.: 5  Endothelium‐dependent relaxation and impact of a Western type diet in the aorta of apolipoprotein E‐deficient mice
Authors: Crauwels H.M. , Van Hove C.E. , Herman A.G. , Bult H.
Published: May 2005

Previously we reported that even in old (18 months) apolipoprotein E‐deficient mice (apoE‐/‐) on regular chow (RC), all nitric oxide (NO)‐mediated responses are preserved in plaque‐free vessels. Only when plaques develop, localised vasomotor dysfunction occurs. The impact of increased oxidative stress on relaxations was evaluated by feeding apoE‐/‐ mice either a Western type diet (WD; 0.15% cholesterol, 41% fat) or RC (no cholesterol, 4% fat) for 8, 16 and 24 weeks. The aorta was systematically sectioned and segments of the aortic root (1 mm) and the thoracic aorta (5 × 2 mm, covering whole vessel, varying degrees of atherosclerosis) were studied in organ baths followed by morphometry. The WD enhanced plasma levels of total cholesterol (1382 ± 109 vs. 425 ± 21 mg/dl) and soluble ICAM‐1 (μg/ml; 8 weeks 43 ± 3 vs. 28 ± 1; 16 weeks 37 ± 2 vs. 25 ± 1; 24 weeks 41 ± 4 vs. 29 ± 1). In RC mice, relaxations to exogenous NO and acetylcholine (ACh) were preserved in all segments up to 24 weeks. When fed the WD however, maximum relaxation (Emax) to exogenous NO (acidified NaNO2) was impaired in the aortic root at 8 (83 ± 3 vs. 92 ± 1%), 16 (71 ± 4 vs. 87 ± 3%) and 24 weeks (59 ± 7 vs. 83 ± 1%); shifts in the pD2 values pointed to decreased sensitivity. ACh‐relaxation was unaltered at 8 weeks, but deteriorated in the aortic root at 16 (74 ± 6 vs. 99 ± 1%) and 24 weeks (51 ± 6% vs. 95 ± 3%). Similar changes occurred in the most distal thoracic aorta segment of WD mice. However, in all those segments plaques were detectable, and average lesion size was increased 6‐fold by the WD. Furthermore, responses to ACh (Emax rs = −0.54; pD2 rs = −0.36, P < 0.001) and exogenous NO (Emax rs = −0.59; pD2 rs = −0.30, P < 0.01) inversely correlated to plaque size in WD mice, as previously reported for RC apoE‐/‐ mice. The dysfunction was apparent only after plaque development. Indeed, segments of the central thoracic aorta were largely free of atherosclerosis and showed unaltered relaxation, even after the onset of atherogenesis at 24 weeks WD. In conclusion, the elevation of soluble ICAM‐1 points to enhanced oxidative stress in WD apoE‐/‐ mice. Yet, endothelium‐dependent relaxation is still maintained until plaques develop. As opposed to the human situation, endothelial dysfunction in hypercholesterolemic apoE‐/‐ mice is not a systemic but a local process, strictly associated with lesion formation. Finally, the preservation of vasomotor responses in plaque‐free segments, and the correlation between lesion size and dysfunction, further emphasise that it is crucial to document plaque dimensions in vasomotor studies in atherosclerosis research.
Abstract no.: 6  Endothelium‐dependent relaxation by purinergic receptors in the aorta of apolipoprotein E‐deficient mice
Authors: Korda A. , Guns P.J.D. , Crauwels H.M. , Van Hove C.E. , Holvoet P. , Bult H.
Published: May 2005

Previously we reported that the acetylcholine‐induced relaxation in the isolated aorta of apolipoprotein E‐deficient (apoE‐/‐) mice deteriorates after the development of atherosclerotic plaques, but remains normal in adjacent, plaque‐free segments. The present study investigated the presence of functional purinergic receptors in the murine aorta, and whether their function changes before or after the development of atherosclerosis. Endothelium‐dependent relaxation was measured in aorta segments of apoE‐/‐, C57BL6 (WT) and human apoAI‐overexpressing apoE‐/‐ mice (apoAI/apoE‐/‐) on regular chow. Rings were isometrically contracted with phenylephrine to 50% of their maximum force before performing cumulative concentration‐response curves to different nucleotides or their stable analogues. After the functional study, the cross‐sectional area of the plaque was determined in every segment. The nucleotides induced complete (UTP, UDP, ATP) or partial (ADP) relaxation that was abolished by endothelial cell removal or nitric oxide (NO) synthase inhibition. The responses pointed to the presence of functional P2y1, P2y2 or P2y4 receptors on endothelial cells. RT‐PCR confirmed the presence of P2y1 and P2y4 mRNA in the aorta of WT mice. Nucleotide responses were unaltered in lesion‐free apoE‐/‐ mice (5 months). However, in atherosclerotic segments of apoE‐/‐ mice (18 months), the relaxation to ATP was impaired compared to age‐matched WT controls (maximum amplitude (Emax) 25 ± 14%, n = 6 vs. 90 ± 3%, n = 5, P < 0.01). A similar defect was seen for the stable analogue ATP‐gamma‐S (Emax 36 ± 12% vs. 86 ± 3%, P < 0.01). Atherosclerotic apoE‐/‐ segments were less sensitive to the NO donor spermineNONOate (pD2 6.74 ± 0.18) than WT segments (7.25 ± 0.20), but maximum relaxation was unaltered. In non‐atherosclerotic aorta segments of the same apoE‐/‐ mice all relaxation responses remained normal and were not different from WT. Strong negative correlations (P < 0.001) existed between lesion size and the Emax for ATP (rs = −0.82) and ATP‐gamma‐S (rs = −0.73) in apoE‐/‐ mice. ApoAI overexpression improved the purinergic responses (Emax ATP 64 ± 9%, ATP‐gamma‐S 64 ± 10%, n = 5) and these were not different from WT (P > 0.05). An analysis of covariance with plaque size as covariate suggested that this benefit was secondary to the strongly reduced plaque formation in apoAI/apoE‐/‐ mice. It is concluded that functional P2 y receptors are present on murine aortic endothelium. Furthermore, endothelium‐dependent purinergic relaxation declines after plaque development. This deterioration involves decreased bioavailability of NO rather than enhanced ATP degradation. The defect is, however, not systemic since the responses remain unaltered in plaque‐free segments of atherosclerosis‐prone apoE‐/‐ mice.
Abstract no.: 7  Effects of gestational day 11 exposure to methylazoxymethanol acetate on Morris water maze performance, prepulse inhibition and latent inhibition in adult male Wistar rats
Authors: de Bruin N.M.W.J. , Talamini L.M. , Mahieu M. , Patel T. , Ashton D.
Published: May 2005

In the present study, gestating dams were treated with methylazoxymethanol acetate (MAM). MAM causes DNA damage, and this mechanism kills actively dividing neurons and thereby disrupts neurogenesis. This has been considered to be a neurodevelopmental animal model of schizophrenia (Talamini et al. 1998, Brain Res. 789:293–306). Schizophrenic patients show deficits in learning/memory function, sensorimotor gating and latent inhibition. Our aim was to investigate whether we could observe similar deficits in adult offspring of MAM‐treated dams.

Methods:  Pregnant Wistar rats received an injection of either solvent or 20 mg/kg (IP) of MAM on the 11th day of gestation. 12 hours later, the rats received a second injection with either saline or MAM. Four groups of animals were tested at adult age (>75 days old): (1) offspring of untreated naïve mothers; (2) offspring of mothers that received two solvent injections (sol/sol); (3) offspring of mothers that first received MAM and solvent with the second injection (MAM/sol); (4) offspring of mothers subjected to two MAM injections (MAM/MAM). The Morris water maze test was used as a measure for spatial learning and mnemonic capabilities. Sensorimotor gating was studied by means of the prepulse inhibition (PPI) paradigm. Finally, the latent inhibition (conditioned taste aversion) paradigm was used to assess learned irrelevance.

Results:  (1) Animals learned to find the invisible platform in the Morris water maze. MAM did not disrupt acquisition in this test. There were also no differences in long‐term spatial memory in the Morris water maze probe trial. (2) Treatment groups did not differ in the level of PPI or startle reactivity. (3) No effects of MAM treatment were found on latent inhibition. (4) However, there was a difference in body weight between treatment groups: MAM/sol animals had a lower body weight than animals from the naïve group and MAM/MAM rats were significantly lower in weight compared to both the naïve and sol/sol animals.

Conclusion:  Gestational day 11 exposure to MAM did not disrupt learning/memory function, prepulse inhibition or latent inhibition in adult male Wistar rats. The lack of effects of MAM on the above mentioned behavioral parameters in the present study brings into question the relevance of this model for the cognitive and information processing aspects of schizophrenia.
Abstract no.: 8  Two daily administrations of glibenclamide or nateglinide for three days to normal rats fail to affect the glycemic and insulinemic responses to glucose or the same antidiabetic agents
Authors: Oguzhan B. , Jurysta C. , Jijakli H. , Courtois P. , Sener A. , Malaisse W.J.
Published: May 2005

Glibenclamide and nateglinide are two antidiabetic agents belonging, respectively, to the sulfonylurea and meglitinide family. The major aim of the present study was to investigate whether the prior administration twice daily for three days of these agents to normal rats affects the plasma D‐glucose and insulin responses to either enteral D‐glucose or the same diabetic agents. Glibenclamide (1.0 μg/g body wt.) or nateglinide (50.0 μg/g body wt.) was given by gastric tubing mixed with 2.0 ml of a 0.5 % solution of carboxymethylcellulose. D‐glucose (15 μmol/g body wt.) was administered as a 3.5 M solution. Except for a lower plasma D‐glucose concentration in the glibenclamide group, no significant difference was found between the three groups of rats on the morning of the fourth day. Likewise, the plasma D‐glucose and insulin responses to either D‐glucose or the antidiabetic agents were not significantly different in control, glibenclamide‐ and nateglinide‐pretreated rats. The time course for the increase in plasma insulin concentration and lowering of plasma D‐glucose concentration was characterized by earlier peak and nadir values, respectively, in the rats receiving nateglinide rather than glibenclamide. These findings indicate that, in normal rats, the secretory responsiveness of insulin‐producing cells and glucose homeostasis are not significantly affected by mid‐term administration of either glibenclamide or nateglinide, despite the different time course of their effects on both insulin secretion and glycemia.
The pharmacology, toxicology, and medical treatment of sulphur mustard poisoning
Authors: Balali‐Mood Mahdi , Hefazi Mehrdad
Published: May 2005

Sulphur mustard (SM) is regarded as one of the most important agents of chemical warfare because of its simple and cheap chemical synthesis that makes it readily available for both terrorist and military use. SM acts as an alkylating agent that induces disruption of nucleic acids and proteins, impairing cell homeostasis and eventually causing cell death. It rapidly reacts with ocular, respiratory and cutaneous tissues, as well as bone marrow and the mucosal cells of the gastrointestinal tract, resulting in several devastating long‐term effects on human health, many of which are not clinically or pathologically well defined. In light of the possible threat of SM use against military and civilian populations, physicians should be aware of its grave effects and knowledgeable how to care for its victims. The pattern of immediate and long‐term toxic effects following exposure to SM is reviewed in this article with special references to the recent data available from over 100 000 chemical casualties incurred during the Iran–Iraq conflict.
The application of sample pooling methods for determining AUC, AUMC and mean residence times in pharmacokinetic studies
Authors: Cheung Belinda W.Y. , Cartier Linda L. , Russlie Henry Q. , Sawchuk Ronald J.
Published: May 2005

For high‐throughput screening in drug development, methods that can reduce analytical work are desirable. Pooling of plasma samples from an individual subject in the time domain to yield a single sample for analysis has been used to estimate the area under the concentration–time curve (AUC). We describe a pooling procedure for the estimation of the area under the first moment curve (AUMC). The mean residence time (MRT), and where intravenous dosing has been used, the steady‐state volume of distribution can then be determined. Plasma samples from pharmacokinetic studies in dogs and humans analyzed in our laboratory were used to validate the pooling approach. Each plasma sample containing a prokinetic macrolide and three of its metabolites was first analyzed separately, and AUCs and AUMCs were calculated using the linear trapezoidal rule. The procedures for the estimation of AUC by sample pooling have been reported by Riad et al. [Pharm. Res. (1991) vol. 8, pp. 541–543]. For the estimation of AUMC, the volume taken from each of n samples to form a pooled sample is proportional to tn(tn+1 − tn−1), except at t0 where the aliquot volume is 0 and at tlast where the aliquot volume is proportional to tlast(tlast − tlast−1). AUMC to tlast is equal to Cpooled × T2/2, where T is the overall experimental time (tlast − t0). The ratio between AUMC and AUC yields the mean residence time (MRT). Bivariate (orthogonal) regression analysis was used to assess agreement between the pooling method and the linear trapezoidal rule. Bias and root mean square error were used to validate the pooling method. Orthogonal regression analysis of the AUMC values determined by pooling (y‐axis) and those estimated by the linear trapezoidal rule (x‐axis) yielded a slope of 1.08 and r2 of 0.994 for the dog samples; slope values ranged from 0.862 to 0.928 and r2 values from 0.838 to 0.988 for the human samples. Bias, expressed as percentage, ranged from −25.1% to 14.8% with an overall average of 1.40%. The results support the use of a pooled‐sample technique in quantitating the average plasma concentration to estimate areas under the curve and areas under the first moment curve over the sampling time period. Mean residence times can then be calculated.
Justification for routine screening of pharmaceutical products in immune function tests: a review of the recommendations of Putman et al. (2003)
Authors: Ryle Peter R.
Published: May 2005

In a recent publication by Putman et al. (2003), salmeterol, morphine/methadone and buprenorphine were quoted as examples of pharmaceutical drugs whose immunotoxicity has only been revealed by conduct of specific immune function tests in non‐clinical studies. Review of the published non‐clinical data for these drugs has shown that there is no clear evidence of immunotoxicity of salmeterol in these studies, and in addition, there are no clinical issues regarding adverse immunological effects of this drug. Of the opioid drugs, only very minor evidence of immunosuppression by morphine, and marginal evidence of slight immunostimulation by buprenorphine were detected in the non‐clinical immune function assays performed at high doses. Methadone showed no effects on immune function assays in animals. As some immunomodulation by opioid drugs might have been expected based on the known pharmacological properties of this drug class, the marginal effects, or lack of effects observed in the immune function tests does raise a question about the sensitivity and specificity of the assays to detect clinically relevant changes. This review has suggested that, based on the cited examples, there is no strong case for routine non‐clinical immune function testing of all new pharmaceutical products. A more rigorous evaluation of non‐clinical immune function tests, and their ability to discriminate between clinically relevant and non‐clinically relevant immunosuppression, is needed before definitive regulatory guidance in this area can be finalized.
Modeling the interaction of parties, activists and voters: Why is the political center so empty?
Authors: SCHOFIELD NORMAN , SENED ITAI
Published: May 2005

Abstract.  The formal stochastic model of voting should be the theoretical benchmark against which empirical models can be gauged. A standard result in the formal model is the ‘mean voter theorem’ stating that parties converge to the electoral center. Empirical analysis based on the vote‐maximizing premise, however, invalidates this convergence result. We consider both empirical and formal models that incorporate exogeneous valence terms for the parties. Valence can be regarded as an electorally perceived attribute of each party leader that is independent of the policy position of the party. We show that the mean voter theorem is valid for empirical multinomial logit and probit models of a number of elections in the Netherlands and Britain. To account for the non‐centrist policy positions of parties, we consider a more general formal model where valence is also affected by the behavior of party activists. The results suggest that non‐convergent policy choice by party leaders can be understood as rational, vote‐maximizing calculation by leaders in response to electoral and activist motivations.
Is extreme right‐wing populism contagious? Explaining the emergence of a new party family
Authors: RYDGREN JENS
Published: May 2005

Abstract.  This article presents a new model for explaining the emergence of the party family of extreme right‐wing populist parties in Western Europe. As the old master frame of the extreme right was rendered impotent by the outcome of the Second World War, it took the innovation of a new, potent master frame before the extreme right was able to break electoral marginalization. Such a master frame – combining ethnonationalist xenophobia, based on the doctrine of ethnopluralism, with anti‐political‐establishment populism – evolved in the 1970s, and was made known as a successful frame in connection with the electoral breakthrough of the French Front National in 1984. This event started a process of cross‐national diffusion, where embryonic extreme right‐wing groups and networks elsewhere adopted the new frame. Hence, the emergence of similar parties, clustered in time (i.e., the birth of a new party family) had less to do with structural factors influencing different political systems in similar ways as with cross‐national diffusion of frames. The innovation and diffusion of the new master frame was a necessary, but not a sufficient, condition for the emergence of extreme right‐wing populist parties. In order to complete the model, a short list of different political opportunity structures is added.
A theory of coalitions and clientelism: Coalition politics in Iceland, 1945–2000
Authors: INDRIDASON INDRIDI H.
Published: May 2005

Abstract.  This article serves a dual purpose. First, it provides detailed information about coalition formation and termination in Iceland from 1945 to 2000 following closely the format of Wolfgang Müller and Kaare Strøm (eds), Coalition Politics in Western Europe (New York: Oxford University Press, 2000), which considers the other Western European democracies. The political landscape of Iceland is surveyed, as is the institutional framework that structures the formation of coalitions, coalition governance and cabinet termination while providing complete data for each cabinet. Second, the effects clientelism has on coalition politics through the inflated importance of the executive office are considered. The patterns of coalition politics in the Nordic countries are compared to offer preliminary evidence supporting the theory.
Calcitonin therapy in postmenopausal osteoporosis: effects on serum levels of interleukin‐1, interleukin‐6 and tumor necrosis factor‐α
Authors: ÖZORAN K. , SEÇKIN Ü. , TUTKAK H. , MERMERCI B.
Published: May 2005

Background:  It has been suggested that the effects of calcitonin (CT) therapy for senile and postmenopausal osteoporosis were due to its modulatory effects on bone‐related cytokines. A significantly increased release of IL‐1, IL‐6 and TNF‐α, which have bone resorptive effects, has been reported in osteoporotic patients.

Aim:  In this study we investigated the effects of CT therapy on the levels of IL‐1, IL‐6 and TNF‐α.

Method:  Forty postmenopausal osteoporotic women were included to the study. The first group consisting of 20 patients were given 100 IU CT subcutaneously and 1000 mg elemental calcium for 15 consecutive days. The second group or the control group also consisting of 20 patients were only given 1000 mg elemental calcium and both of the groups were not allowed to take any other medication.

Results:  In the first group the mean serum TNF‐α level significantly decreased from 16.9 ± 24.2 pg/mL to 8.6 ± 13 pg/mL after 1500 IU CT therapy (P < 0.05). The control group's mean serum level of IL‐1, IL‐6 and TNF‐α did not reveal any statistically significant differences (P > 0.05).

Conclusion:  Our results suggest that CT therapy for osteoporosis may partially be due to its inhibitory effects on TNF‐α, and probably IL‐1. However, further in‐vitro and ex‐vivo studies are needed to clarify this hypothesis.
Lack of association of antineutrophil cytoplasmic antibodies with joint failure as indicated by joint surgery in rheumatoid arthritis
Authors: BROADFOOT Andrew , GILLIS David , PROUDMAN Susanna
Published: May 2005

Aim:  The objective of this study was to investigate a possible association in rheumatoid arthritis (RA) of perinuclear antineutrophil cytoplasmic antibodies (pANCA) and joint failure requiring joint surgery as a well‐defined functional end point.

Methods:  188 patients with RA according to the American College of Rheumatology criteria, with a mean duration of disease of 18 years, were enrolled in a cross‐sectional study. Patients were assessed for history of joint surgery, previous/current therapies, function according to the modified Health Assessment Questionnaire (mHAQ), rheumatoid factor (RF) and clinical and laboratory parameters of disease activity. ANCA were detected using indirect immunofluorescence.

Results:  Overall, 36.7% of patients were pANCA positive (including atypical pANCA) and 35.1% of patients had a history of joint surgery. There was no association between the presence of pANCA and joint surgery. No association was demonstrated between ANCA status and other prognostic markers such as RF, previous or current therapies and disease activity or function.

Conclusion:  No association between pANCA and joint surgery was demonstrated in this cohort of RA patients.
Up‐regulation of 5‐HT2 Serotonin Receptor: A Possible Mechanism of Transformed Migraine
Authors: Srikiatkhachorn Anan , Govitrapong Piyarat , Limthavon Chanchira
Published: May 2005

SYNOPSIS

Transformation of episodic migraine to chronic daily headache (so called transformed migraine) ia now a well recognized phenomenon. Although several factors, i.e. analgesic overuse, increasing age, psychiatric disorders are reported to play some roles in this transformation, the precise cascade is still unclear. Further suppression of an already abnormal antinociceptive system with up‐regulation of post‐synaptic receptors is one of the possible explanation. In order to understand the mechanism underlying this condition, 5‐HT2 serotonin receptors on platelets were assayed by the radioligand binding technique. Six transformed migraine patients (67.67 ± 1.52 years) and seven healthy controls (72.86 ± 1.82 years) were studied. [3H]‐spiperone and ketanserin were used to determine the specific binding. We found a significant increase (P <0.05) in the maximal receptor numbers (Bmax ) on platelet membrane of the migraine patients when compared to the controls (64.31 ± 11.06 end 39.96 ± 5.42 fmol/mg protein, respectively), whereas the dissociation equilibrium constant (K D ) values remained unchanged (3.63 ± 0.78 nM and 2.84 ± 0.48 nM for the migraine patients and controls, respectively). The up‐regulation of serotonin receptors found in this study provided further support to the ”serotonergic hypofunction“ theory of migraine pathogenesis and may explain the unusual loss of episodicity seen in the transformed migraine patients.
Quantitative EEG in Children with Headache
Authors: Valdizán J.R. , Andreu C. , AImárcegui C. , Olivito A.
Published: May 2005

SYNOPSIS

The object of this work is to determine if Brain Mapping can reveal significant differences between a normal control group and e group whose members suffer from one of three types of headache: tension‐type, migraine with aura and migraine without aura. Both groups were formed by children aged between 6 and 14; the latter were undergoing no treatment and were in a headache‐free phase.

Results demonstrate that there are no significant differences between the control group and the tension‐type headache group. Neither were differences found in migraine without aura group but in migraine with aura there was an increase of the theta/alpha ratio in the temporal posterior and occipital zones. This ratio could be used as a neurophysiological indicator in the evolution of the migraine with aura pathology.
Basilar Migraine With Severe EEG Abnormalities
Authors: Passier Patricia , Vredeveld Jan W. , de Krom Marc
Published: May 2005

SYNOPSIS

We report a patient suffering from a series of attacks fulfilling the criteria of basilar migraine. During the attack there was no normal EEG background pattern and the EEG showed predominantly delta activity. After the attack the EEG returned to (nearly) normal in a very short time. Up to now no such EEG findings have been reported in basilar migraine.
Evaluation and Treatment of Headache Patients in the Emergency Department: A Survey.
Authors: Barton Christopher W.
Published: May 2005

SYNOPSIS

Patients with headache represent a common diagnostic and treatment challenge for health care providers in the emergency department. The therapeutic options continue to grow, yet many studies imply that narcotics continue to be a frequently chosen treatment. In this retrospective cross‐sectional survey, the evaluation and treatment patterns of patients presenting to an academic medical center emergency department with a primary diagnosis of headache were analyzed. Headache disorders accounted for 1.7% of all visits to the emergency department. Migraine headache was the most common headache diagnosis representing 60% of headache visits followed by headache of no obvious source at 25%. Narcotics were the most common treatment employed (180 patient‐visits) in all patients and non‐steroidal anti‐inflammatory agents were the second most common agent used (86 patient visits). Narcotics were also the most common therapy in migraine headache patients (152 patient‐visits) while ergotamines were used in less than one‐third of patient‐visits (36 patient‐visits). Therapy of headache patients in the emergency department continues to rely on narcotics. Methods of interrupting the dependence on narcotics need to be explored if newer non‐narcotic therapies are to be successful.
Pseudoaneurysm Within the Cavernous Sinus Presenting as Cluster Headache
Authors: Koenigsberg Adam D. , Solomon Glen D. , Kosmorsky Gregory
Published: May 2005

SYNOPSIS

Cluster headache and its associated signs end symptoms have been described in medical literature for years. The etiology of this condition remains unresolved. We describe a unique patient who presented with a cluster headache syndrome concurrent with new‐onset pseudoaneurysm within the cavernous sinus. Our review and analysis of this patient confirms current theories which describe the role of the cavernous sinus as a locus of pathology in cluster headache.
SUNCT Syndrome: Repetitive and Overlapping Attacks
Authors: Pareja Juan A. , Pareja Julia , Palomo Tomás , Caballero Vicente , Pamo Manuel
Published: May 2005

SYNOPSIS

A 79‐year‐old patient had been suffering from right orbital pain attacks since he was 77. The pain, of an “electrical” or burning character, was moderate to severe in intensity. Single attacks lasted for 30–60 seconds each and were accompanied by prominent ipsilateral conjunctival injection and tearing as well as slight rhinorrhoea. The temporal pattern of attacks was irregular with spontaneous remissions alternating with unpredictable symptomatic phases. During active periods, attacks could be triggered by several precipitants acting on trigeminal and extra‐trigeminal innervated areas. On most occasions, the patient had 2–3 attacks daily but, at worst, he might have almost continuous short‐lasting attacks in periods of 1 to 3 hours length. When attacks had such frequency they presented either as repetitive or overlapping single episodes. According to the clinical features it is concluded that the case reported is a new case of SUNCT syndrome.
The Diagnosis Of Headache in Primary Care: Factors in the Agreement of Clinical and Standardized Diagnoses
Authors: Stang Paul E. , Korff Michael Von
Published: May 2005

SYNOPSIS

Objective: Comparison of clinical headache diagnoses in primary care to algorithm diagnoses from a standardized headache interview.

Design: A sample of consecutive primary care headache patients (n=779) at the Group Health Cooperative of Puget Sound were interviewed and medical records abstracted.

Measurements: The medical record provided ‘chart’ diagnoses while a structured interview and diagnostic algorithm yielded the ‘algorithm diagnosis’. The patients were also administered the depression sub‐scale from the SCL 90‐R, in addition to answering questions about pain intensity and disability used to rade the severity of chronic pain.

Results: Among persons diagnosed by the primary care physician as having migraine, 78% received an algorithm diagnosis of migraine. However, study patients were more likely to receive a diagnosis of migraine by algorithm (57%) than by clinical diagnosis (33%). While clinicians infrequently recorded a diagnosis of migraine and tension‐type headache in the same patients, tension‐type headache was identified among half of the algorithm diagnosed migraineurs. Among patients with algorithm‐diagnosed migraine, female gender, increased isability, and the presence of aura increased the likelihood that the clinician would also diagnose migraine, Conversely, the presence of tension‐type headache features, high levels of depression, high number of headache days and age over 65 years reduced the likelihood of the clinician diagnosing migraine among algorithm‐diagnosed cases.

Conclusions: The co‐occurrence of migraine and tension‐type headache symptoms are commonly reported by patients, however, primary care physicians usually recorded a single diagnosis of either migraine or tension headache. Among patients reporting migrainous features, the presence of chronic headache, emotional distress and the absence of disability reduced the likelihood that the clinician would assign a diagnosis of migraine. These results suggest the need for diagnostic and management strategies appropriate for patients whose headaches combine tension‐type and migrainous features,
Does Quality of Life Differ Among Headache Diagnoses? Analysis Using the Medical Outcomes Study Instrument
Authors: Solomon Glen D. , Skobieranda Franck G. , Gragg Lisa A.
Published: May 2005

SYNOPSIS

Background: To analyze the differences in quality of life associated with headache diagnoses using the Medical Outcomes Study Short Form Health Survey (SF‐20).

Methods: A patient interview survey using the SF‐20 Short Form Health Survey was conducted in a headache clinic within a multi‐specialty group practice. All six health components of the SF‐20 were included in the study, Headache diagnoses were made using IHS criteria.

Results: 208 consecutive headache patients were studied. Patients with cluster headache had a significantly higher (worse) pain score (P<0.018) and higher percentage of patients with poor health due to pain (P<0.005) than patients with migraine headache. There were fewer cluster patients with poor health associated with physical functioning than tension‐type (P<0.020) or mixed headache (P<0.022) patients. Poor health associated with social functioning was greater for cluster (P<0.011) and tension‐type headache (P<0.015) than for migraine. There was a significantly higher percentage of tension‐type headache patients with poor health associated with mental health (P<0.002) than patients with migraine.

Conclusions: The SF‐20 is a reliable and valid measure of quality of life for patients with different headache diagnoses. Distinct headache diagnoses are marked by unique patterns of impairment and quality of life.
Transcranial Doppler Sonography in Headache‐Free Migraineurs
Authors: Abernathy Margaret , Donnelly Gerard , Kay Gary , Wieneke Jacqueline , Morris Sarah , Bergeson Scott , Ramos Maria , Call Diana , O'Rourke Daniel
Published: May 2005

SYNOPSIS

We used transcranial Doppler ultrasonography to determine whether intracranial blood velocities in 182 headache‐free migraineurs (60 with aura, 122 without aura) differed from velocities in 38 nonheadache prone control subjects. During the headache‐free period, migraineurs with and without aura had significantly elevated mean velocities in all intracranial arteries except the right internal carotid artery at the level of the siphon. Velocities in migraineurs with aura did not differ significantly from velocities in those without aura.

Markedly increased velocities were noted in a subset of interictal migraineurs. Two explanations are possible: 1) Blood flow velocities may increase in response to a decrease in the cross sectional area of a vessel st or near the point of insonation. 2) Alterations at the level of the cerebral arteriole may affect regional cerebral blood flow, thereby changing blood flow velocities at the point of insonation. Transcranial Doppler sonography alone cannot sort out which process is responsible for the vascular response.

This work may have therapeutic as well as diagnostic implications. When interictal flow velocities are markedly increased, it is possible that therapeutic agents with vasoconstrictor action might cause an excessive response. Further study is needed to clarify the sites of vasoreactivity as well as the magnitude of drug‐induced vasoconstrictor response.