bluuebunny/crossref_metadata_2025 huggingface dataset:
Co‐localization of IgA and TG3 on healthy skin of coeliac patients
Authors: Cannistraci C , Lesnoni La Parola I , Cardinali G , Bolasco G , Aspite N , Stigliano V , Picardo M
Published: January 2007

Background  Dermatitis herpetiformis (DH), the skin's expression of coeliac disease (CD), is induced by the presence of IgA antibodies and epidermal transglutaminase (TG3) as the main autoantigen, stored in the papillary dermis and on the vessel walls.

Aims  To evaluate the presence of IgA and TG3 deposits, considered to be the first step in inducing DH, in healthy skin of coeliac patients without cutaneous manifestations.

Methods  Punch biopsies were taken from 11 consecutive coeliac patients, two with DH and nine without cutaneous manifestations, three of whom were adhering to a gluten‐free diet (GFD), and evaluated for the presence of deposits in the upper dermis and vessel walls by immunofluorescence and confocal microscopy.

Results  In coeliac patients affected by DH we found the presence of IgA and TG3 deposits mainly on the upper dermis, but also in vessel walls. In all coeliac patients without DH and also in those patients who were following a strict GFD, we found widely variable deposits of IgA and TG3 in both the papillary dermis and the vessel walls, although a lower intensity of the fluorescence signal was detected than with coeliac patients affected by DH. Double immunostaining with anti‐IgA and anti‐TG3 antibodies showed a strong co‐localization in the upper dermis in patients with DH and a weaker co‐localization in those without DH.

Conclusions  We have demonstrated the presence of IgA and TG3 deposits in the healthy skin of coeliac patients, which are considered to play a central role in the pathogenesis of DH.
Clinical and histopathological findings of ‘psoriatic neurodermatitis’ and of typical lichen simplex chronicus
Authors: Gunasti S , Marakli SS , Tuncer I , Ozpoyraz N , Aksungur VL
Published: January 2007

Background  We have seen several patients with itchy lichenified plaques located bilaterally on the elbows and/or knees and have named this condition ‘psoriatic neurodermatitis’ (PN).

Objective  The purpose of this study was to compare clinical and histopathological characteristics of these patients to those of patients with typical lichen simplex chronicus (LSC).

Methods  Nineteen patients with PN and 34 patients with typical LSC were included. Besides clinical dermatological evaluation, the prick test was carried out on 49 patients; the Phadiatop test on 40 patients; the patch test with European standard series on 47 patients; histopathological evaluation on 39 patients; and clinical psychiatric examination on 38 patients.

Results  Almost exclusively, PN was seen in females and was located on the extremities. It caused more plaques than typical LSC did. In PN, the plaques were smaller, sharper, more keratotic and less excoriated, and had fewer lichenoid papules around them. Itching was usually more severe in the evening, while resting and in a hot environment in typical LSC, but not in PN. In plaques of PN, microabscesses in the horny layer, hypogranulosis, regular acanthosis and thinning of the suprapapillary plates were more frequent, and hyperpigmentation in the basal layer was less. In patients with PN, depressive disorder was found more frequently; and generalized anxiety disorder or psychosomatic characteristics, less. There were no significant differences in the results of prick, Phadiatop and patch tests between patients with PN and those with typical LSC.

Conclusion  In our opinion, it is most likely that the so‐called PN is itchy psoriasis superimposed by LSC.
A series of melanomas smaller than 4 mm and implications for the ABCDE rule
Authors: Goldsmith SM , Solomon AR
Published: January 2007

Background  Although multiple studies have reported that a significant number of melanomas have diameters of less than or equal to 6 mm at the time of diagnosis, there has been only one series evaluating the proportion of melanomas less than 4 mm in diameter.

Objective  The objective of this study was to determine the proportion of melanomas, in a single‐practitioner, general dermatology practice, with clinical diameters less than 4 mm.

Methods  Information regarding each new diagnosis of melanoma had been recorded during the study period of 2000–2004. Patient records and pathology reports were examined from these patients.

Results  Thirteen (13.7%) of the 95 melanomas had diameters less than 4 mm at the time of presentation, including five invasive and eight in situ melanomas. The defining clinical characteristic of these lesions was intensity of pigment. Three of these 13 melanomas, including one invasive and two in situ lesions, showed features of regression.

Conclusions  The findings of this study support those authors who have suggested elimination of the 6‐mm diameter criterion in the ABCDE rule. In addition, this study provides further evidence that dark colour as a diagnostic criterion for melanoma should be given more emphasis. The substitution of ‘D’ to represent dark instead of diameter is worthy of consideration to enhance the value of the ABCDE mnemonic.
Plant resistance to parasitic plants: molecular approaches to an old foe
Authors: Rispail N. , Dita M.‐A. , González‐Verdejo C. , Pérez‐de‐Luque A. , Castillejo M.‐A. , Prats E. , Román B. , Jorrín J. , Rubiales D.
Published: January 2007

Parasitic weeds pose severe constraint on major agricultural crops. Varying levels of resistance have been identified and exploited in the breeding programmes of several crops. However, the level of protection achieved to date is either incomplete or ephemeral. Resistance is mainly determined by the coexistence of several mechanisms controlled by multigenic and quantitative systems. Efficient control of the parasite requires a better understanding of the interaction and their associated resistance mechanisms at the histological, genetic and molecular levels. Application of postgenomic technologies and the use of model plants should improve the understanding of the plant–parasitic plant interaction and drive not only breeding programmes through either marker‐assisted selection (MAS) or transgenesis but also the development of alternative methods to control the parasite. This review presents the current approaches targeting the characterization of resistance mechanisms and explores their potentiality to control parasitic plants.
Breeding status, contaminant burden and helminth parasites of Northern FulmarsFulmarus glacialisfrom the Canadian high Arctic
Authors: MALLORY MARK L. , MCLAUGHLIN J. DANIEL , FORBES MARK R.
Published: January 2007

We studied the relationship between contaminant concentrations in livers, endohelminth prevalence and physiological indices of chronic stress (spleen size, heterophil/lymphocyte ratios) in Northern FulmarsFulmarus glacialiscollected during the breeding season in Nunavut, Canada. No blood parasites were found, similar to reports for other petrel species elsewhere. However, 54% of Fulmars had gastrointestinal helminths, principally cestodes (52% prevalence, mean intensity of 11 worms), nematodes (34% prevalence, 3.6 worms) and acanthocephalans (3%, eight worms). Both prevalence and intensity of helminth infections were lower for Arctic Fulmars than for Fulmars and other petrels found in southern parts of the species’ range. Spleen size was not significantly related to either contaminant concentration or presence of parasites, suggesting that Fulmar health was generally unaffected by contaminant and parasite levels at the colony. However, we cannot rule out the possibility that Fulmars with higher parasitaemias or contaminant loads were in poorer condition and did not attend the breeding colony.
Adhesion to the extracellular matrix is positively regulated by retinoic acid in HepG2 cells
Authors: Massimi Mara , Devirgiliis Laura Conti
Published: January 2007

Aims: In this work, we aimed to investigate the possible modulation of cell–matrix interactions by retinoic acid (RA), in view of the well‐known role of the extracellular matrix (ECM) and integrins in hepatocyte differentiation and proliferation. For this purpose, we analysed the adhesion ability of HepG2 cells on different substrates in the presence and absence of RA evaluating both the expression and cellular localisation of major proteins involved in focal contacts, using Western blot and confocal microscopy.

Results: A positive and substrate‐dependent effect of RA on cell–matrix adhesion was observed after long‐term culture. The increased adhesiveness in the treated cells was accompanied by an enhanced expression of β1 and α3 integrin subunits, together with a redistribution of β1 receptors clustered at the basal surface. In contrast, the levels of focal adhesion kinase (FAK), paxillin and α‐actinin were unchanged, as was the phosphorylation state of FAK. Nonetheless, a stronger association between β1 integrin and intracytoplasmatic proteins of focal contacts was observed in coimmunoprecipitation experiments after RA treatment, suggesting improved connection with the actin cytoskeleton. These results are consistent with previously described antiproliferative and differentiative effects of RA on transformed hepatocytes, and confirm the hypothesis of a direct influence of RA on specific adhesion molecules.
Recurrence of primary sclerosing cholangitis after living donor liver transplantation
Authors: Tamura Sumihito , Sugawara Yasuhiko , Kaneko Junichi , Matsui Yuichi , Togashi Junichi , Makuuchi Masatoshi
Published: January 2007

Background/aims: Cumulative experience in deceased donor liver transplantation for end‐stage liver disease due to primary sclerosing cholangitis (PSC) suggests that liver transplantation is the treatment of choice with excellent results. Reports on the outcome of live donor liver transplantation (LDLT) for PSC, however, remain anecdotal.

Methods: The clinical course and genetic disposition of nine patients who underwent LDLT for PSC were analyzed. The median follow‐up period was 3.5 years.

Results: Cumulated 5‐year patient and graft survival rates were 90% and 71%, respectively. Recurrent PSC was diagnosed in four patients. Ratios of freedom from recurrent PSC at 1, 3, and 5 years were 100%, 73%, and 49%, respectively. The mean time to recurrence was 3.3 years. Excluding the one case with a biologically unrelated donor, recurrent PSC was diagnosed in 50% (4/8). None of the patients presented with the human leukocyte antigen‐B8DR3 haplotype, which is associated with a higher susceptibility for developing PSC among the Caucasian population. Overall patient survival of LDLT for PSC seems to equal that of deceased donor liver transplantation.

Conclusions: PSC might recur earlier at a higher ratio after LDLT. Further study with protocol cholangiogram and genetic considerations, including high resolution human leukocyte antigen haplotype analysis, is necessary.
Efficacy of adefovir dipivoxil in the treatment of lamivudine‐resistant hepatitis B virus genotype C infection
Authors: Kim Do Young , Kim Hong Jeoung , Lee Chun Kyon , Suh Jeong Hun , Kim Dong Hwan , Cho Yong Suk , Won Sun Young , Park Byung Kyu , Park In Suh
Published: January 2007

Background and Aims: Adefovir dipivoxil (ADV) is a nucleotide analogue that is known to be effective for lamivudine‐resistant hepatitis B virus (HBV) mutants as well as wild‐type HBV. The aim of this study is to assess the efficacy of ADV against lamivudine‐resistant genotype C HBV mutants.

Methods: Thirty‐five patients with breakthrough hepatitis due to lamivudine‐resistant HBV received ADV 10 mg daily with discontinuation of lamivudine. Quantitative HBV DNA, HBeAg, liver function test including alanine aminotransferase (ALT) was checked every 4–12 weeks to evaluate the efficacy of ADV.

Results: ADV was administered for a median of 48 weeks (range: 24–120 weeks). The rate of serum HBV DNA loss was 68.6%, 80.0%, 84.0%, and 88.2% at weeks 12, 24, 36, and 48, respectively. The rate of serum HBeAg seroconversion was 8.3% and 14.3% at weeks 24 and 48, respectively. The rate of serum ALT normalization at week 48 was 70.6%. Within 32 weeks after stopping ADV therapy, serum HBV DNA levels increased to a median of 378.9 pg/ml in 88.9% of patients, who were treated for a median of 40 weeks. Moreover, in some patients, the ALT level increased to more than five times the upper limit of normal.

Conclusions: Administration of ADV is an effective option for the treatment of patients with lamivudine‐resistant genotype C HBV infection.
Natural products and chronic hepatitis C virus
Authors: Azzam H. S. , Goertz C. , Fritts M. , Jonas W. B.
Published: January 2007

Background: Chronic hepatitis C virus (HCV) infection is a significant public health problem, with a worldwide prevalence of approximately 170 million. The standard of care for chronic HCV, a combination of α‐interferon (IFN) and ribavirin, is only 50% effective, has serious side effects, and can be prohibitively expensive for low‐income countries with a high prevalence of HCV. Many patients use natural products, including those who are not eligible for IFN/ribavirin, cannot afford treatment, or fail to respond to IFN.

Methods: Extensive literature searches were conducted in order to identify clinical trials and reviews of natural products used for treatment of chronic HCV. This review focuses on the composition, pharmacology and results of clinical trials of three natural products: Oxymatrine, TJ‐108/schisandra/Gomisin A and lactoferrin.

Results: Several laboratory and human studies have been performed to evalaute these alternative treatments, but many of these studies are small, uncontrolled and have other important design flaws. While they do offer some safety and efficacy data, none of these studies is conclusive.

Conclusion: Further research is needed on the effectiveness of these natural products for treatment of chronic HCV, including their preparation and standardization.
A comprehensive gene expression analysis of human hepatocellular carcinoma cell lines as components of a bioartificial liver using a radial flow bioreactor
Authors: Kosuge Makoto , Takizawa Hiroko , Maehashi Haruka , Matsuura Tomokazu , Matsufuji Senya
Published: January 2007

Background/Aims: The cells constituting a bioartificial liver are crucial for an effective liver support system. We compared global gene expression profiles in a radial flow bioreactor or a monolayer culture of three functional liver cell lines previously established from human hepatocellular carcinoma.

Methods: The expressions of 60 000 genes of the FLC‐4, FLC‐5, and FLC‐7 cell lines were analyzed by the microarray technique with the Affymetrix GeneChip system. Global gene expression profiles were compared with two‐way cluster analysis. Several liver function‐related genes were compared between the bioreactor and culture conditions.

Results: Cluster analysis revealed that gene expression profiles of bioreactor‐grown cells resembled those of the normal liver. Genes related to cellular structure were highly expressed in the bioreactor‐grown cells, while genes involved in proliferation or carcinogenesis were suppressed. In the bioreactor‐grown cells, some genes for liver functions were expressed at a level similar to that in normal liver, although none of the cell lines expressed the complete set of genes encoding ammonium metabolism or cytochrome P450 species.

Conclusion: The high‐density three‐dimensional culture in the radial flow bioreactor prompted differentiation of the cells. These data may be useful for improving the cells by genetic or pharmacological reinforcement and for monitoring bioartificial livers.
Comparison of 7‐day and 14‐day Proton Pump Inhibitor‐Containing Triple Therapy for Helicobacter pylori Eradication: Neither Treatment Duration Provides Acceptable Eradication Rate in Korea
Authors: Kim Byeong Gwan , Lee Dong Ho , Ye Byong Duk , Lee Kwang Hyuck , Kim Beung Wook , Kim Sang Gyun , Kim Sang Woo , Kim Sung Kook , Kim Jae J. , Kim Hak Yang , Park Jong Jae , Park Chang Young , Baik Gwang Ho , Lee Yong Chan , Lee Jun Haeng , Lee Jin Hyug , Chun Hoon Jai , Hahm Ki Baik , Hong Su Jin , Lee Sang Woo , Jung Hyun Chae
Published: January 2007

Background and Aims:  Although triple combination therapy containing a proton pump inhibitor (PPI) and two antibiotics is considered as a standard regimen for the first‐line anti‐Helicobacter pylori treatment, there are still debates on the ideal duration of treatment. The aim of this study was to compare the efficacies of 7‐day and 14‐day PPI‐containing triple therapy.

Materials and Methods:  This study was performed in a randomized, multicenter, prospective manner. After upper gastrointestinal endoscopy, H. pylori‐infected patients with a gastric ulcer and/or a duodenal ulcer were randomly assigned to a PAC7 group (omeprazole 20 mg or equivalent dose of other PPIs, amoxicillin 1000 mg, and clarithromycin 500 mg twice daily for 7 days) or to a PAC14 group (the same regimen as the PAC7 group but for 14 days). H. pylori status was evaluated by 13C urea breath test 5 weeks after anti‐ulcer treatment completion.

Results:  A total of 598 patients were enrolled; 337 were randomized to the PAC7 group and 261 to the PAC14 group. The two groups were comparable in terms of baseline characteristics. The eradication rates of the PAC7 group were not inferior to those of the PAC14 group in both intention‐to‐treat analysis (71.2% vs. 75.5%) and per‐protocol analysis (83.6% vs. 86.6%). Incidences of adverse events were comparable.

Conclusions:  Although the 7‐day PPI‐containing triple anti‐H. pylori therapy is not inferior to the 14‐day therapy, neither treatment duration provides acceptable eradication rate reaching 90% in per‐protocol analysis. New combination regimen with higher efficacy should be developed as a first‐line eradication therapy for H. pylori in Korea.
Migraine, Helicobacter pylori, and Oxidative Stress
Authors: Tunca Ayşe , Ardıçoğlu Yasemin , Kargılı Ayşe , Adam Bahattin
Published: January 2007

Background:  The aim of this study was to ascertain whether oxidative stress is a causative factor of migraine attacks for Helicobacter pylori‐infected migraineurs.

Materials and Methods:  A total of 35 consecutive migraine patients without aura who came to gastroenterology polyclinic with various complaints and diagnosed H. pylori infection were included in the study group and compared with a group of 29 patients (control group) without migraine and H. infection. H. pylori infection was diagnosed by histopathological biopsies, which were taken by endoscopy (Olympus‐GIFXQ240 endoscope). Both the diagnosis and the classification of migraine were made according to the International Headache Society criteria.

 Blood samples for nitric oxide were taken from patients with migraine during headache‐free period as well as the control group.

 The interaction of nitric oxide was measured by the determination of both nitrite and nitrate concentrations in the sample.

Results:  The study group included 31 women and 4 men (mean age 49 ± 8 years) and the control group included 25 women and 4 men (mean age 52.6 ± 11 years). The mean frequency of migraine attacks was 2.94 ± 1.58 days/month and the mean duration of attacks was 21.2 ± 3 hours.

 It was found that the study group has lower nitrate levels than the control group.

Conclusions:  Our results do not support the role of oxidative stress in patients suffering from H. pylori infection and migraine.
Levofloxacin‐ vs. Ranitidine Bismuth Citrate‐Containing Therapy After H. pylori Treatment Failure
Authors: Gisbert Javier P. , Gisbert Jose Luis , Marcos Santiago , Moreno‐Otero Ricardo , Pajares Jose Maria
Published: January 2007

Aim:  Ranitidine bismuth citrate and levofloxacin‐based regimen may be an alternative to quadruple therapy after Helicobacter pylori eradication failure. Our aim was to compare two 7‐day triple second‐line regimens containing ranitidine bismuth citrate or levofloxacin.

Methods:  Patients in whom a first eradication trial with omeprazole‐clarithromycin‐amoxicillin had failed were randomized to receive 7‐day treatment with: 1, ranitidine bismuth citrate (400 mg b.i.d.), tetracycline (500 mg q.i.d.), and metronidazole (250 mg q.i.d.), or 2, levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.), and omeprazole (20 mg b.i.d.). Cure rates were evaluated by 13C‐urea breath test.

Results:  One‐hundred patients were included: 50 received the ranitidine bismuth citrate regimen, and 50 the levofloxacin one. Groups were comparable in terms of demographic variables. Two percent of the patients (one in each group) did not return for follow up. Compliance was similar in both groups (90% took all the medications correctly). Side‐effects (only mild/moderate) in the two groups were also comparable (38% with ranitidine bismuth citrate and 36% with levofloxacin). Per‐protocol cure rates were 69% (95% CI = 54–80%) in the ranitidine bismuth citrate group, and 71% (57–82%) in the levofloxacin one. Intention‐to‐treat cure rates were, respectively, 68% (59–79%) and 68% (59–79%) (nonstatistically significant differences).

Conclusions:  Both 7‐day ranitidine bismuth citrate‐ and levofloxacin‐containing second‐line regimens represent alternatives to quadruple therapy in patients with previous omeprazole‐clarithromycin‐amoxicillin failure.
Low Concentrations of Zinc in Gastric Mucosa are Associated with Increased Severity of Helicobacter pylori‐Induced Inflammation
Authors: Sempértegui Fernando , Díaz Myriam , Mejía Ricardo , Rodríguez‐Mora Oswaldo G. , Rentería Edgar , Guarderas Carlos , Estrella Bertha , Recalde Ramiro , Hamer Davidson H. , Reeves Philip G.
Published: January 2007

Background:  Chronic Helicobacter pylori infection is the most common cause of gastric cancer. H. pylori induces oxidative stress while zinc deficiency results in increased sensitivity to it. In Ecuador, the prevalence of gastric cancer and zinc deficiency are high. We hypothesized that zinc deficiency in Ecuadorian people would cause increased H. pylori‐induced inflammation in the gastric mucosa associated with lower tissue zinc concentrations.

Methods:  Three hundred and fifty‐two patients with dyspepsia underwent endoscopy to obtain gastric mucosa biopsies. Diagnosis of H. pylori infection and its severity, histopathology, mucosal zinc concentration, and inflammation intensity were determined.

Results:  H. pylori‐infected patients with non‐atrophic chronic gastritis had lower concentrations of zinc in gastric mucosa than uninfected patients with the same type of gastritis (251.3 ± 225.3 vs. 426.2 ± 279.9 ng/mg of protein; p = .016). Considering all patients, the more severe the H. pylori infection, the higher the percentage of subjects with infiltration by polymorphonuclear (PMN) cells (p = .0001). Patients with high PMN infiltration had lower mucosal zinc concentrations than patients with low PMN infiltration (35.2 ± 20.7 vs. 242.9 ± 191.8 ng/mg of protein; p = .021).

Conclusions:  The degree of inflammation in H. pylori‐induced gastritis appears to be modulated by gastric tissue zinc concentrations.
Hashimoto's Encephalopathy Mimicking Migraine With Aura
Authors: Huete Adolfo Jimenez , Sanchez‐del‐Rio Margarita , Franch Oriol
Published: January 2007

We describe a patient with Hashimoto's encephalopathy presenting as long‐standing episodes of aphasia associated with migraine‐like headache. Repeated thyroid hormone levels were within normal values, but high titers of antithyroid antibodies in serum, and diffuse EEG slowing and CSF abnormalities during one episode led to the diagnosis.
Chronic Daily Headache in a Primary Care Population: Prevalence and Headache Impact Test Scores
Authors: Coeytaux Remy R. , Linville Julie C.
Published: January 2007

Background.—Population‐based surveys estimate the prevalence of chronic daily headache (CDH) in the general community to be approximately 4%. The prevalence of CDH among patients seen in the primary care setting in the United States, however, is unknown.

Purpose.—To estimate the prevalence and associated burden of suffering of CDH in a primary care patient population.

Methods.—Cross‐sectional survey of a randomly selected sample of 1500 adult patients in an academic Family Medicine Center was done. Outcome measures include self‐reported headache frequency and Headache Impact Test scores.

Results.—Completed questionnaires were returned by 853 (57%) patients. The mean age of respondents was 49 years (SD = 16), with a range of 18 to 94 years. Two hundred ninety‐six (58%) patients reported having had 1 or more severe headaches in the past month. Seventy‐four (9%) patients reported a frequency of headache consistent with CDH, defined as the occurrence of headache 15 or more days in the past month. Twenty‐four patients (32%) with CDH either believed that none of their doctors know that they experienced headaches or were not sure if their doctors were aware of their headaches, and 21 (28%) reported that they have not needed a doctor's care for their headaches.

Conclusions.—The prevalence of CDH is greater among a primary care patient population compared to the general community. A substantial proportion of patients with CDH do not bring their headaches to the attention of their health‐care providers. In light of the advances in the development of effective medications for migraines and the growing body of evidence implicating medications as a contributing cause of CDH, it may be appropriate to encourage patients to inform their health‐care providers about their headaches and to encourage providers to identify patients with frequent headaches.
Coenzyme Q10 Deficiency and Response to Supplementation in Pediatric and Adolescent Migraine
Authors: Hershey Andrew D. , Powers Scott W. , Vockell Anna‐Liisa B. , LeCates Susan L. , Ellinor Priscilla L. , Segers Ann , Burdine Danny , Manning Paula , Kabbouche Marielle A.
Published: January 2007

Background.—Coenzyme Q10 (CoQ10) has been suggested to be effective in the prevention of migraine, and levels can be quantified with standardized reference ranges.

Objective.—This study documents the prevalence of CoQ10 deficiency in migraine headache and examines the potential effectiveness of supplementation.

Methods.—We assessed patients attending a tertiary care center with frequent headaches for CoQ10 deficiency. We recommended patients with low CoQ10 levels begin supplementation with CoQ10 as part of their multidisciplinary treatment plan. We assessed response to treatment including correction of CoQ10 deficiency, overall headache improvement, and headache disability.

Results.—CoQ10 was measured in 1550 patients (mean age 13.3 ± 3.5, range 3 to 22 years). The mean total CoQ10 level was 0.60 ± 0.20 μg/mL (range 0.21 to 1.77 μg/mL). Of these patients, 32.9% were below the reference range. Patients with low CoQ10 were recommended to start 1 to 3 mg/kg per day of CoQ10 in liquid gel capsule formulation. In a subset of patients who returned for timely follow‐up (mean, 97 days), the total CoQ10 level improved to 1.20 ± 0.59 μg/mL (P < .0001), while the headache frequency improved from 19.2 ± 10.0 to 12.5 ± 10.8 (P < .001) and headache disability assessed with PedMIDAS improved from 47.4 ± 50.6 to 22.8 ± 30.6 (P < .001).

Conclusions.—Deficiency of CoQ10 may be common in pediatric and adolescent migraine. Determination of deficiency and consequent supplementation may result in clinical improvement. Further analysis involving more scientifically rigorous methodology will be required to confirm this observation.
Antiepileptic Drugs for the Treatment of Chronic and Episodic Cluster Headache: A Review
Authors: Pascual Julio , Láinez Miguel J.A. , Dodick David , Hering‐Hanit Rachel
Published: January 2007

Cluster headache needs to be rapidly diagnosed and effectively managed, as the individual headache attacks that are characteristic of this disorder are excruciatingly painful and debilitating. Preventive therapies are necessary to reduce the frequency of attacks during the cluster period. However, preventive therapy for this disorder is limited by a lack of controlled evidence of efficacy and the potential for systemic toxicity. Recent progress has been made in understanding both the pathophysiological mechanisms underlying cluster headache and the mechanisms of action of the antiepileptic drug class for the treatment of primary headache syndromes. Newly available preliminary clinical trial data evaluating antiepileptic drugs for the prevention of cluster headache suggest that these agents may be effective and that further evaluation in randomized, placebo‐controlled trials is warranted.
Increased Dilator Response to Nitrate and Decreased Flow‐Mediated Dilatation in Migraineurs
Authors: Yetkin Ertan , Ozisik Handan , Ozcan Cemal , Aksoy Yuksel , Turhan Hasan
Published: January 2007

Background.—It has been known that in a migraine attack intracranial and extracranial arteries on the headache side dilate and when the migraine attack has subsided, the intracranial arteries show segmental narrowing. We hypothesized that patients with migraine had an underlying systemic vasomotion abnormality and there might be an increased nitrate‐mediated vasodilatory response in the brachial artery of migraineurs. Accordingly we aimed to measure endothelium dependent and independent functions of brachial artery in migraineurs and healthy subjects.

Materials and Methods.—Twenty‐four patients who fulfilled the diagnostic criteria of migraine were enrolled in the study. Twenty‐six age‐ and sex‐matched healthy control subjects comprised the control group. Flow‐mediated dilatation and nitrate‐mediated dilatation were measured in all patients and control subjects by means of brachial artery ultrasonography.

Results.—Flow‐mediated dilatation of patients with migraine was significantly lower than that of control subjects (7.6 ± 3.7% vs 10.4 ± 3.5%, respectively, P= .008). However, nitrate‐mediated dilatation in migraineurs was significantly higher than that of nonmigraineurs (25% vs 14%, respectively, P< .001).

Conclusion.—We have shown that migraineurs have decreased endothelium dependent function whereas increased nitrate‐mediated response in their brachial artery. It can be suggested that the mechanism underlying migraine may be a diffuse vascular vasomotion abnormalities and migraine may be a local manifestation of systemic vascular abnormality rather than a primary cerebral phenomenon.
Efficacy and Feasibility of a Novel Tri‐Modal Robust Exercise Prescription in a Retirement Community: A Randomized, Controlled Trial
Authors: Baker Michael K. , Kennedy David J. , Bohle Philip L. , Campbell Deena S. , Knapman Leona , Grady Jodie , Wiltshire James , McNamara Maria , Evans William J. , Atlantis Evan , Fiatarone Singh Maria A.
Published: January 2007

OBJECTIVES: To test the feasibility and efficacy of current guidelines for multimodal exercise programs in older adults.

DESIGN: Randomized, controlled trial.

SETTING: Retirement village.

PARTICIPANTS: Thirty‐eight subjects (14 men and 24 women) aged 76.6 ± 6.1.

INTERVENTION: A wait list control or 10 weeks of supervised exercise consisting of high‐intensity (80% of one‐repetition maximum (1RM)) progressive resistance training (PRT) 3 days per week, moderate‐intensity (rating of perceived exertion 11 to 14/20) aerobic training 2 days per week, and progressive balance training 1 day per week.

MEASUREMENTS: Blinded assessments of dynamic muscle strength (1RM), balance, 6‐minute walk, gait velocity, chair stand, stair climb, depressive symptoms, self‐efficacy, and habitual physical activity level.

RESULTS: Higher baseline strength and psychological well‐being were associated with better functional performance. Strength gains over 10 weeks averaged 39±31% in exercise, versus 21±24% in controls (P=.10), with greater improvements in hip flexion (P=.01), hip abduction (P=.02), and chest press (P=.04) in the exercise group. Strength adaptations were greatest in exercises in which the intended continuous progressive overload was achieved. Stair climb power (12.3±15%, P=.002) and chair stand time (−7.1±15%, P=.006) improved significantly and similarly in both groups. Reduction in depressive symptoms was significantly related to compliance (attendance rate r=−0.568, P=.009, PRT progression in loading r=−0.587, P=.02, and total volume of aerobic training r=−0.541, P=.01), as well as improvements in muscle strength (r=−0.498, P=.002).

CONCLUSION: Robust physical and psychological adaptations to exercise are linked, although volumes and intensities of multiple exercise modalities sufficient to cause significant adaptation appear difficult to prescribe and adhere to simultaneously in older adults.
Change in Motor Function and Risk of Mortality in Older Persons
Authors: Buchman Aron S. , Wilson Robert S. , Boyle Patricia A. , Bienias Julia L. , Bennett David A.
Published: January 2007

OBJECTIVES: To assess the association between change in motor function and mortality.

DESIGN: Prospective, observational cohort study.

SETTING: Approximately 40 retirement communities across the Chicago metropolitan area participating in the Rush Memory and Aging Project.

PARTICIPANTS: Eight hundred thirty‐seven community‐based older persons without dementia.

MEASUREMENTS: Change in composite measures of motor performance and muscle strength.

RESULTS: During a mean follow‐up of 2.2 years, 81 persons died. In a proportional hazards model adjusted for age, sex, education, and body mass index, each 1‐unit increase in the level of baseline motor performance was associated with an approximately 10% decrease in risk of mortality (hazard ratio (HR)=0.901, 95% confidence interval (CI)=0.863–0.941), and each unit of annual increase in motor performance was associated with an approximately 11% decrease in the risk of mortality (HR=0.887, 95% CI=0.835–0.942). In a similar model, each 1‐unit increase in the level of baseline strength was associated with an approximately 9% decrease in the risk of mortality (HR=0.906, 95% CI=0.859–0.957), and each 1‐unit annual increase in strength was associated with an approximately 10% decrease in the risk of mortality (HR=0.898, 95% CI=0.809–0.996). These results were similar when men and women were analyzed separately and after controlling for physical activity, cognition, and chronic disorders. When motor performance and muscle strength were examined in a single model, only baseline and annual change in motor performance were associated with mortality.

CONCLUSION: Level and rate of change in strength and motor performance are associated with mortality. The attenuation of the association between strength and mortality by motor performance suggests that motor function is not a unitary process and that its components may vary in their associations with adverse health consequences in older persons.
Risk Factors for Adverse Drug Events in Older Adults with Mobility Limitations in the Community Setting
Authors: Chrischilles Elizabeth , Rubenstein Linda , Van Gilder Rachel , Voelker Margaret , Wright Kara , Wallace Robert
Published: January 2007

OBJECTIVES: To investigate risk factors for self‐reported adverse drug events (ADEs) in a cohort of annually surveyed Iowa Medicare beneficiaries with mobility limitations.

DESIGN: Prospective cohort study with baseline and two annual follow‐up questionnaires.

SETTING: Population‐based sample of Iowa Medicare beneficiaries with mobility limitations.

PARTICIPANTS: Members of the cohort with complete follow‐up questionnaires and prescription dispensing data (N=689).

MEASUREMENTS: The questionnaires asked about self‐reported ADEs in the previous 12 months, sociodemographic data, smoking, alcohol use, number of mobility limitations, and history of chronic disease. Pharmacy dispensing records were the source of number and classes of prescription drug use. Linked Medicare claims provided additional comorbidity data.

RESULTS: Of the 689 subjects, 151 (21.9%) reported an ADE, 83% of which resulted in physician contact and 56% of which resulted in discontinuing the medication. Number of different medications dispensed during the prior year was an independent predictor of a self‐reported ADE. Neither age, extent of mobility limitation, nor number of chronic conditions was independently associated with reporting an ADE.

CONCLUSION: Excess ADE risk observed with increasing mobility limitations is mediated through greater medication use.
A Distributed Parameter Physiologically‐Based Pharmacokinetic Model for Dermal and Inhalation Exposure to Volatile Organic Compounds
Authors: Roy A. , Weisel C. P. , Lioy P. J. , Georgopoulos P. G.
Published: January 2007

Estimates of dermal dose from exposures to toxic chemicals are typically derived using models that assume instantaneous establishment of steady‐state dermal mass flux. However, dermal absorption theory indicates that this assumption is invalid for short‐term exposures to volatile organic chemicals (VOCs). A generalized distributed parameter physiologically‐based pharmacokinetic model (DP‐PBPK), which describes unsteady state dermal mass flux via a partial differential equation (Fickian diffusion), has been developed for inhalation and dermal absorption of VOCs. In the present study, the DP‐PBPK model has been parameterized for chloroform, and compared with two simpler PBPK models of chloroform. The latter are lumped parameter models, employing ordinary differential equations, that do not account for the dermal absorption time lag associated with the accumulation of permeant chemical in tissue represented by permeability coefficients. All three models were evaluated by comparing simulated post‐exposure exhaled breath concentration profiles with measured concentrations following environmental chloroform exposures. The DP‐PBPK model predicted a time‐lag in the exhaled breath concentration profile, consistent with the experimental data. The DP‐PBPK model also predicted significant volatilization of chloroform, for a simulated dermal exposure scenario. The end‐exposure dermal dose predicted by the DP‐PBPK model is similar to that predicted by the EPA recommended method for short‐term exposures, and is significantly greater than the end‐exposure dose predicted by the lumped parameter models. However, the net dermal dose predicted by the DP‐PBPK model is substantially less than that predicted by the EPA method, due to the post‐exposure volatilization predicted by the DP‐PBPK model. Moreover, the net dermal dose of chloroform predicted by all three models was nearly the same, even though the lumped parameter models did not predict substantial volatilization.
The Constrained Extremal Distribution Selection Method
Authors: Lenox Michael J. , Haimes Yacov Y.
Published: January 2007

Engineering design and policy formulation often involve the assessment of the likelihood of future events commonly expressed through a probability distribution. Determination of these distributions is based, when possible, on observational data. Unfortunately, these data are often incomplete, biased, and/or incorrect. These problems are exacerbated when policy formulation involves the risk of extreme events—situations of low likelihood and high consequences. Usually, observational data simply do not exist for such events. Therefore, determination of probabilities which characterize extreme events must utilize all available knowledge, be it subjective or observational, so as to most accurately reflect the likelihood of such events. Extending previous work on the statistics of extremes, the Constrained Extremal Distribution Selection Method is a methodology that assists in the selection of probability distributions that characterize the risk of extreme events using expert opinion to constrain the feasible values for parameters which explicitly define a distribution. An extremal distribution is then “fit” to observational data, conditional that the selection of parameters does not violate any constraints. Using a random search technique, genetic algorithms, parameters that minimize a measure of fit between a hypothesized distribution and observational data are estimated. The Constrained Extremal Distribution Selection Method is applied to a real world policy problem faced by the U.S. Environmental Protection Agency. Selected distributions characterize the likelihood of extreme, fatal hazardous material accidents in the United States. These distributions are used to characterize the risk of large scale accidents with numerous fatalities.
Customer Perceptions of Agency Risk Communication
Authors: Fisher Ann , Chen Ya‐Chin
Published: January 2007

A government agency commissioned a baseline study of how its customers view the agency's risk information. The 70% response rate to a mail survey allows analysis by subgroups representing customers’primary interests. Although this agency traditionally has been responsible for ensuring plant and animal health at the farm gate (or where imported), responses emphasized emerging customer concerns about the environment and human health. Customers think many risk communication activities are important, but that the agency is not especially effective in conducting those activities. Customers are moderately satisfied with much of the risk information they receive, although many have little contact from or interaction with the agency. Customers identified other sources they use, which suggest potentially effective channels for this agency's risk messages. The study provides a baseline for measuring change in the agency's risk communication effectiveness. It also can be a model when other organizations plan their own risk communication evaluations.
A Comparison of Two Statistical Approaches to Estimate Long‐Term Exposure Distributions from Short‐Term Measurements
Authors: Slob Wout
Published: January 2007

Two statistical approaches are briefly reviewed, both of which are suitable for estimating interindividual variation in long‐term exposure: a recently published regression approach and the standard ANOVA approach. Simulation studies illustrate the performances of the two approaches in estimating the relevant parameters. Their relative advantages and applicability are discussed. It is concluded that when repeated exposure measurements from the same individuals are available, ANOVA is preferable. The regression approach however has its place because it can be applied to certain data types where ANOVA does not apply.
Derivation of a Target Concentration of Pb in Soil Based on Elevation of Adult Blood Pressure
Authors: Stern Alan H.
Published: January 2007

The increase in systolic blood pressure in males appears to be the most sensitive adult endpoint appropriate for deriving a health risk‐based target level of lead (Pb) in soil. Because the response of blood pressure to blood Pb concentration (PbB) has no apparent threshold, traditional approaches based on the application of a Reference Dose (RfD) are not applicable. An alternative approach is presented based on a model which predicts the population shift in systolic blood pressure from ingestion of Pb contaminated soil as a simultaneous function of exposure to Pb in soil, the baseline distribution of blood Pb concentration in the population and the baseline distribution of systolic pressure in the population. This model is analyzed using Monte Carlo analysis to predict the population distribution of systolic pressure resulting from Pb exposure. Based on this analysis, it is predicted that for adult males 18‐65 years old, exposure to 1000 ppm Pb in soil will result in an increase of approximately 1 mm Hg systolic pressure, an increase in the incidence of systolic hypertension (i.e., systolic pressure >140 mm Hg) of approximately 1% and an increase in PbB of 1–3 μg/dl. Based on the proposition that these adverse effects can be considered de minimis, 1000 ppm Pb in soil is proposed as a target soil concentration for adult exposure. Available data do not appear to be adequate to predict the newborn PbB level which would result from exposure to this soil level during pregnancy.

SUMMARY AND CONCLUSIONS

The increase in systolic blood pressure in adult males appears to be a reasonable health endpoint for the derivation of a target soil level of Pb for sites (such as those on industrial land) where exposure of children is precluded. Pb soil levels protective against a non‐de minimis increase in systolic pressure should also be protective against other known adverse adult endpoints. Based on the available data it is predicted that a concentration of 1000 μg Pb/g soil will result in a de minimis population‐based increase in systolic blood pressure where ingestion is the only significant route of soil exposure. Significant uncertainty exists as to the appropriate input distributions for some of the parameters in this model. As additional data become available, they can be used to refine this analysis.
Uncertainty and the Value of Information with Stochastic Losses from Global Warming
Authors: Peck Stephen C. , Teisberg Thomas J.
Published: January 2007

We present an uncertainty analysis conducted using CETA‐R, a model in which the costs of climate change are specified as Risks of large losses. In this analysis, we assume that three key parameters may each take on “high” or “low” values, leading to eight possible states of the world. We then explore optimal policies when the state of the world is known, and under uncertainty. Also, we estimate the benefits of resolving uncertainty earlier. We find that the optimal policy under uncertainty is similar to the policy that is optimal when each of the key parameters is at its low value. We also find that the value of immediate uncertainty resolution rises sharply as the alternative to immediate resolution is increasingly delayed resolution.
Who Holds the Stakes? A Case Study of Stakeholder Identification at Two Nuclear Weapons Production Sites
Authors: Boiko Patricia E. , Morrill Richard L. , Flynn James , Faustman Elaine M. , Belle Gerald van , Omenn Gilbert S.
Published: January 2007

Traditional risk assessments, including those involving the United States Department of Energy (USDOE), are often criticized for producing useless or noncredible management responses because they did not meaningfully involve the public. The first step to involve the public is to identify appropriate active participants (stakeholders). This study was done to understand the processes used to identify stakeholders to serve on advisory boards established at the two largest remediation sites in the United States: the Hanford Nuclear Reservation in Washington state and the Savannah River Site in South Carolina. The Hanford stakeholder identification process produced an interest‐based board whereas the Savannah River Site strategy produced population‐based representation. The basic goals of the stakeholder advisory groups were similar. However, different processes were used to identify the participants for the groups in part because of distinctly different social and cultural conditions in the areas affected by the operations of the two facilities, and in part because of the different level of trust of the USDOE and their contractors at Hanford compared with Savannah River. The discussion analyzes their different needs and potential for successful citizen participation.
Credibility, Information Preferences, and Information Interests
Authors: Jungermann Helmut , Pfister Hans‐Rüdiger , Fischer Katrin
Published: January 2007

The Seveso Directive of the European Union demands that information be provided to the public by companies and authorities about facts, risks, and behaviors related to hazardous facilities, in particular chemical facilities. On behalf of the Commission of the European Communities, a survey was run in five European countries on the credibility of various information sources. This article describes the results of the German study. 430 persons were interviewed with a questionnaire of 50 items, in particular about their perceptions and evaluations of technical risks, the credibility of sources of information about chemical risks, their preferences for receiving risk information from these sources, and their interests in receiving information. Major findings are great differences in credibility, differentiated information preferences, and strong information interests. Surprisingly, credibility played only a minor role with regard to the respondents’information preferences and interests.