bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjusting for Regression Effect in Uncontrolled Studies
Authors: Naranjo Joshua D. , McKean Joseph W.
Published: May 2004

Summary. When clinical studies require enrolled patients to have abnormal assays, the natural tendency of repeat measurements to regress toward the mean can lead to a false assessment of effectiveness of therapy. We propose a method to more accurately estimate the true effect of therapy by adjusting for a component of improvement that can be attributed to regression effect. The model we use allows for a combination of additive and/or multiplicative effects of the therapy.
Estimation of Population Attributable Fractions from Fitted Incidence Ratios and Exposure Survey Data, with an Application to Electromagnetic Fields and Childhood Leukemia
Authors: Greenland Sander
Published: May 2004

Summary. Standard presentations of epidemiological results focus on incidence‐ratio estimates derived from regression models fit to specialized study data. These data are often highly nonrepresentative of populations for which public‐health impacts must be evaluated. Basic methods are provided for interval estimation of attributable fractions from model‐based incidence‐ratio estimates combined with independent survey estimates of the exposure distribution in the target population of interest. These methods are illustrated in estimation of the potential impact of magnetic‐field exposures on childhood leukemia in the United States, based on pooled data from 11 case‐control studies and a U.S. sample survey of magnetic‐field exposures.
Detecting Interaction Between Random Region and Fixed Age Effects in Disease Mapping
Authors: Dean C. B. , Ugarte M. D. , Militino A. F.
Published: May 2004

Summary.The purpose of this article is to draw attention to the possible need for inclusion of interaction effects between regions and age groups in mapping studies. We propose a simple model for including such an interaction in order to develop a test for its significance. The assumption of an absence of such interaction effects is a helpful simplifying one. The measure of relative risk related to a particular region becomes easily and neatly summarized. Indeed, such a test seems warranted because it is anticipated that the simple model, which ignores such interaction, as is in common use, may at times be adequate. The test proposed is a score test and hence only requires fitting the simpler model. We illustrate our approaches using mortality data from British Columbia, Canada, over the 5‐year period 1985–1989. For this data, the interaction effect between age groups and regions is quite large and significant.
On the Use of the Variogram in Checking for Independence in Spatial Data
Authors: Diblasi A. , Bowman A. W.
Published: May 2004

Summary.The variogram is a standard tool in the analysis of spatial data, and its shape provides useful information on the form of spatial correlation that may be present. However, it is also useful to be able to assess the evidence for the presence of any spatial correlation. A method of doing this, based on an assessment of whether the true function underlying the variogram is constant, is proposed. Nonparametric smoothing of the squared differences of the observed variables, on a suitably transformed scale, is used to estimate variogram shape. A statistic based on a ratio of quadratic forms is proposed and the test is constructed by investigating the distributional properties of this statistic under the assumption of an independent Gaussian process. The power of the test is investigated. Reference bands are proposed as a graphical follow‐up. An example is discussed.
TheK‐Function for Nearly Regular Point Processes
Authors: Taylor Charles C. , Dryden Ian L. , Farnoosh Rahman
Published: May 2004

Summary.We propose modeling a nearly regular point pattern by a generalized Neyman‐Scott process in which the offspring are Gaussian perturbations from a regular mean configuration. The mean configuration of interest is an equilateral grid, but our results can be used for any stationary regular grid. The case of uniformly distributed points is first studied as a benchmark. By considering the square of the interpoint distances, we can evaluate the first two moments of the K‐function. These results can be used for parameter estimation, and simulations are used to both verify the theory and to assess the accuracy of the estimators. The methodology is applied to an investigation of regularity in plumes observed from swimming microorganisms.
An Evaluation of Semiautomatic Approaches to Contour Segmentation Applied to Fungal Hyphae
Authors: Inglis Iain M. , Gray Alison J.
Published: May 2004

Summary. Semiautomatic image analysis techniques are particularly useful in biological applications, which commonly generate very complex images, and offer considerable flexibility. However, systematic study of such methods is lacking; most research develops fully automatic algorithms. This paper describes a study to evaluate several different semiautomatic or computer‐assisted approaches to contour segmentation within the context of segmenting degraded images of fungal hyphae. Four different types of contour segmentation method, with varying degrees and types of user input, are outlined and applied to hyphal images. The methods are evaluated both quantitatively and qualitatively by comparing results obtained by several test subjects segmenting simulated images qualitatively similar to the hyphal images of interest. An active contour model approach, using control points, emerges as the method to be preferred to three more traditional approaches. Feedback from the image provider indicates that any of the methods described have something useful to offer for segmentation of hyphae.
Minimizing Model Fitting Objectives That Contain Spurious Local Minima by Bootstrap Restarting
Authors: Wood Simon N.
Published: May 2004

Summary. Objective functions that arise when fitting nonlinear models often contain local minima that are of little significance except for their propensity to trap minimization algorithms. The standard methods for attempting to deal with this problem treat the objective function as fixed and employ stochastic minimization approaches in the hope of randomly jumping out of local minima. This article suggests a simple trick for performing such minimizations that can be employed in conjunction with most conventional nonstochastic fitting methods. The trick is to stochastically perturb the objective function by bootstrapping the data to be fit. Each bootstrap objective shares the large‐scale structure of the original objective but has different small‐scale structure. Minimizations of bootstrap objective functions are alternated with minimizations of the original objective function starting from the parameter values with which minimization of the previous bootstrap objective terminated. An example is presented, fitting a nonlinear population dynamic model to population dynamic data and including a comparison of the suggested method with simulated annealing. Convergence diagnostics are discussed.
A Marginal Likelihood Approach for Estimating Penetrance from Kin‐Cohort Designs
Authors: Chatterjee Nilanjan , Wacholder Sholom
Published: May 2004

Summary.The kin‐cohort design is a promising alternative to traditional cohort or case‐control designs for estimating penetrance of an identified rare autosomal mutation. In this design, a suitably selected sample of participants provides genotype and detailed family history information on the disease of interest. To estimate penetrance of the mutation, we consider a marginal likelihood approach that is computationally simple to implement, more flexible than the original analytic approach proposed by Wacholder et al. (1998,American Journal of Epidemiology148, 623–629), and more robust than the likelihood approach considered by Gail et al. (1999,Genetic Epidemiology16, 15–39) to presence of residual familial correlation. We study the trade‐off between robustness and efficiency using simulation experiments. The method is illustrated by analysis of the data from the Washington Ashkenazi Study.
Nonparametric Mixed Effects Models for Unequally Sampled Noisy Curves
Authors: Rice John A. , Wu Colin O.
Published: May 2004

Summary.We propose a method of analyzing collections of related curves in which the individual curves are modeled as spline functions with random coefficients. The method is applicable when the individual curves are sampled at variable and irregularly spaced points. This produces a low‐rank, low‐frequency approximation to the covariance structure, which can be estimated naturally by the EM algorithm. Smooth curves for individual trajectories are constructed as best linear unbiased predictor (BLUP) estimates, combining data from that individual and the entire collection. This framework leads naturally to methods for examining the effects of covariates on the shapes of the curves. We use model selection techniques—Akaike information criterion (AIC), Bayesian information criterion (BIC), and cross‐validation—to select the number of breakpoints for the spline approximation. We believe that the methodology we propose provides a simple, flexible, and computationally efficient means of functional data analysis.
Catch Estimation in the Presence of Declining Catch Rate Due to Gear Saturation
Authors: Dauk Philip C. , Schwarz Carl J.
Published: May 2004

Summary. One strategy for estimating total catch is to employ two separate surveys that independently estimate total fishing effort and catch rate with the estimator for total catch formed by their product. Survey designs for estimating catch rate often involve interviewing the fishermen during their fishing episodes. Such roving designs result in incomplete episode data and characteristically have employed a model in which the catch rate is assumed to be constant over time. This article extends the problem to that of estimating total catch in the presence of a declining catch rate due, e.g., to gear saturation. Using a gill net fishery as an example, a mean‐of‐ratios type of estimator for the catch rate together with its variance estimator are developed. Their performance is examined using simulations, with special attention given to effects of restrictions on the roving survey window. Finally, data from a Fraser River gill net fishery are used to illustrate the use of the proposed estimator and to compare results with those from an estimator based on a constant catch rate.
Lichen Striatus: Clinical and Laboratory Features of 115 Children
Authors: Patrizi Annalisa , Neri Iria , Fiorentini Cristina , Bonci Angela , Ricci Giampaolo
Published: May 2004

Abstract:  To analyze the clinical features, response to treatment, and follow‐up of lichen striatus and any associated symptoms or disease, we designed a retrospective study involving 115 affected children at the Pediatric Dermatology Unit of the Department of Dermatology of the University of Bologna, Bologna, Italy. Between January 1989 and January 2000 we diagnosed lichen striatus in 37 boys and 78 girls (mean age 4 years 5 months). We studied their family history and the season of onset, morphology, distribution, extent, duration, histopathology, and treatment of their lichen striatus. We found that family history was negative in all our patients except for two pairs of siblings. The majority of children had the disease in the cold seasons; precipitating factors were found in only five cases. The most frequently involved sites were the limbs, with no substantial difference between upper and lower limb involvement. When lichen striatus was located on the trunk and face, it always followed Blaschko lines; in seven children the bands on the limbs appeared to be along the axial lines of Sherrington. In 70 cases, lichen striatus was associated with atopy. The mean duration of the disease was 6 months and relapses were observed in five children, and in one instance the disease had a prolonged course. Only a few case study series of lichen striatus in children have been reported and ours is the largest to date. The etiology of lichen striatus remains unknown in the majority of our patients. The confirmed association with atopy observed in our patients may be a predisposing factor. It has generally been accepted that lichen striatus follows the lines of Blaschko, and this distribution is a sign of both a topographic and a pathogenetic concept. In patients where lichen striatus is along axial lines, a locus minoris resistentiae, we suppose that this distribution may only be an illusory phenomenon in instances in which the trigger factor prefers this route, consisting of several successive Blaschko lines, but appearing as a single band.
Dermatitis Artefacta in Pediatric Patients: Experience at the National Institute of Pediatrics
Authors: Saez‐de‐Ocariz Marimar , Orozco‐Covarrubias Luz , Mora‐Magaña Ignacio , Duran‐McKinster Carola , Tamayo‐Sanchez Lourdes , Gutierrez‐Castrellon Pedro , Ruiz‐Maldonado Ramon
Published: May 2004

Abstract:  Dermatitis artefacta is a factitious disorder in which there is deliberate conscious production of skin lesions. There are only a few reports that evaluate instances of dermatitis artefacta in the pediatric population. The aim of this retrospective study was to assess the characteristics of patients with this disorder who were seen at the National Institute of Pediatrics in Mexico City. The records of all patients diagnosed with dermatitis artefacta from January 1980 to December 1999 were analyzed. There were 29 patients (25 females, 4 males). The upper limbs and the face were the most commonly involved areas. Superficial erosions were the most frequent initial event, and residual lesions consisted of scars and crusts. Time taken to diagnosis was on average 10 months. Half of the patients were lost to follow‐up. No correlation was found between the length of time from the disease onset to diagnosis, the type of lesions, and the clinical outcome. Twelve patients had an associated systemic disorder. The possible association with chronic disease has not been sufficiently stressed and demonstrates the importance of providing psychological support for these patients. Psychiatric diagnoses were anxiety, depression, and personality disorder. No correlation was found between the psychiatric diagnosis and the outcome of dermatitis artefacta. A young age at presentation, which has been considered important as a favorable prognostic sign, could not be demonstrated in our patients.
Acetaminophen‐Induced Toxic Epidermal Necrolysis in a Child
Authors: Bygum Anette , Gregersen Jon Waarst , Buus Sanne Krogsbøll
Published: May 2004

Abstract:  Toxic epidermal necrolysis (TEN) is a severe, life‐threatening disorder that usually affects adults. It is often drug induced. We report an instance of a severe case of TEN in a 6‐year‐old boy, probably induced by acetaminophen, and less likely by codeine. A lymphocyte stimulation test could not identify the culprit drug. Treatment with intravenous immunoglobulin seemed to halt the disease progression.
Mercury Intoxication: It Still Exists
Authors: Beck Carolyn , Krafchik Bernice , Traubici Jeffrey , Jacobson Sheila
Published: May 2004

Abstract:  A 3‐year‐old boy presented to the Hospital for Sick Children with systemic symptoms and oropharyngeal and peripheral extremity changes suggestive of Kawasaki disease. He was found to have severe hypertension. Investigation for a catecholamine‐secreting tumor was negative. Toxins were considered when the patient's 20‐month‐old brother presented with similar symptoms, and the boys were subsequently diagnosed with elemental mercury poisoning. We review the literature on mercury intoxication and discuss the historical context, clinical syndrome (acrodynia), treatment, and radiologic findings of this unusual diagnosis.
Flushing Due to Solitary Cutaneous Mastocytoma can be Prevented by Hydrocolloid Dressings
Authors: Yung Anthony
Published: May 2004

Abstract:  Solitary mastocytomas occur commonly and can occasionally be associated with troublesome flushing related to rubbing. We report a child with a solitary mastocytoma who repeatedly and reproducibly caused flushing only with rubbing and scratching. Conventional treatment with antihistamines was not completely effective and caused sedation. A trial application of double‐layer hydrocolloid dressing led to complete abolition of flushing episodes until the child reached an age where he could peel off the dressings. This treatment is particularly suited to very young children with solitary mastocytomas whose parents do not feel comfortable with antihistamine treatment, topical or intralesional corticosteroids, or surgical interventions. This treatment may be used alone or in conjunction with conventional therapy where there has been a failure to achieve complete control of flushing and/or blistering.
Molecular diversity and phylogenetic analysis of mariner‐like transposons in the genome of the silkworm Bombyx mori
Authors: Kumaresan G. , Mathavan S.
Published: May 2004

Genome‐wide screening of mariner‐like elements (MLEs) in the silkworm Bombyx mori has revealed the presence of five different types of MLEs (Bmmar1, Bmmar2, Bmmar3, Bmmar4 and Bmmar5). We isolated and characterized sixty copies of the MLEs representing the five Bmmar types. Their nucleotide sequences, nucleotide compositions, deduced transposase sequences, codon preferences, and the copy numbers showed extensive variations. Phylogenetic analysis of the sequences revealed that Bmmar1, Bmmar2, and Bmmar3 have been in the B. mori genome for a long time, while Bmmar4 is probably a recent invader of the genome. Because of the long‐term association of Bmmar1 and Bmmar2 with the genome, highly mutated miniature Bmmar1 and Bmmar2 are widespread in the genome, and the footprints of these elements are also present in different silkworm genes. However, miniature copies of Bmmar4 were not detected. This recently acquired element has very few mutations. None of the characterized copies had functional transposase open reading frames. They essentially exist as fossils in the genome.
Molecular characterization of insulin‐like peptide genes and their expression in the African malaria mosquito, Anopheles gambiae
Authors: Krieger M. J. B. , Jahan N. , Riehle M. A. , Cao C. , Brown M. R.
Published: May 2004

Of the seven genes encoding insulin‐like peptides (ILPs) in the mosquito, Anopheles gambiae, four are arrayed proximally as duplicate pairs on chromosome three. Amino acid substitutions encoded in the duplicate genes occur in the C peptide and not the B and A peptides. Except for one duplicated gene, sequence‐specific transcripts for all other AgamILPs were obtained from female mosquitoes. Transcript expression of each AgamILP was determined by RT‐PCR in the head, thorax, and abdomen of all life stages and both sexes of this mosquito. Two AgamILPs were ubiquitously expressed, suggesting a growth factor function, whereas the other AgamILPs were expressed primarily in heads, as confirmed by the immunostaining of ILPs in the neurosecretory cells of female brains, thus indicating a hormonal function.
Strain‐specific quantification ofWolbachiadensity inAedes albopictusand effects of larval rearing conditions
Authors: Dutton T. J. , Sinkins S. P.
Published: May 2004

The density of the endosymbiontWolbachiacan influence the expression of the crossing sterilities known as cytoplasmic incompatibility (CI), and also its rate of maternal transmission.Aedes albopictusmosquitoes contain a superinfection with theWolbachiastrainswAlbA andwAlbB. A strain‐specific real‐time quantitative PCR assay was developed and used to quantify relativeWolbachiastrain densities within individual mosquitoes. ThewAlbB strain was consistently found to be at higher density thanwAlbA, which can explain a slightly lower rate of maternal transmission reported forwAlbA. The effects of larval crowding and nutritional stress were also examined. Larval crowding always reduced adult size, but reduced the density ofWolbachiastrains relative to uncrowded conditions only if crowding was accompanied by restricted nutrient availability. Crowded rearing conditions never resulted in strain segregation or in a reduction in the penetrance of CI, however. The rate of maternal transmission and the penetrance of CI are the two most important variables that determine relativeWolbachiapopulation invasion dynamics, and both are considerably higher here than have been reported in theDrosophila simulansmodel system.
Disaster Exercise Outcomes for Professional Emergency Personnel and Citizen Volunteers
Authors: Perry Ronald W.
Published: May 2004

It has long been argued in the research literature that conducting disaster exercises produces a variety of benefits that promote effective emergency management. In spite of nearly universal acceptance of the claim, there are few empirical studies that have explored the effects of exercises on participants. This paper reviews the role of exercises in the creation of community disaster preparedness, while making explicit the links among planning, training and exercising. Using a quasi‐experimental design, the effects of disaster exercise participation on perceptions of response knowledge and teamwork are studied for police officers, fire‐fighters and civilian volunteers. The exercise studied involved an annual airport disaster drill required for continuing certification. It was found that participation enhanced the perceptions of response knowledge and teamwork for all three types of participants.
Book Reviews
Authors: Short James F. , Marchi Bruna de , Yand Seung‐Bum , Stern Eric , Barton Laurence
Published: May 2004

Books Reviewed:

Christopher Hood, Henry Rothstein and Robert Baldwin, The Government of Risk: Understanding Risk Regulation Regimes

Kathleen J. Thierney, Michael K. Lindell, and Ronald W. Perry, Facing the Unexpected: Disaster Preparedness and Response in the United States

Frank‐Jürgen Richter, Redesigning Asian Business: In the Aftermath of Crisis

Rhona Flin and Kevin Arbuthnot (Eds), Incident Command: Tales From the Hot Seat

Rachel Briggs (Ed.), The Unlikely Counter‐Terrorists
Age at Acquisition of Helicobacter pylori Infection: Comparison of Two Areas with Contrasting Risk of Gastric Cancer
Authors: Camargo M. Constanza , Yepez M. Clara , Ceron Cristina , Guerrero Nancy , Bravo Luis E. , Correa Pelayo , Fontham Elizabeth T.H.
Published: May 2004

Background.  Helicobacter pylori infection is usually acquired during childhood and is a known risk factor for the development of gastric malignancies in adulthood. It has been reported that early age at first infection may determine a neoplastic outcome in adults. The purpose of this study was to determine the prevalence of Helicobacter pylori infection in children residing in areas with high (Pasto) and low risk (Tumaco) of gastric cancer in Colombia to evaluate whether differences in the age of acquisition of H. pylori infection were present in the two populations.

Materials and Methods.  The study sample was based on a census taken in 1999. Using the 13C‐urea breath test, we compared the prevalence of H. pylori infection among children aged 1–6 years.

Results.  Among 345 children in Pasto, 206 (59.7%) were H. pylori‐positive, compared with 188 (58.6%) among 321 children in Tumaco. The two populations share a common pattern of very early age at infection and marked increase in prevalence during the first 4 years of life. No differences in any one year were observed when comparing the two groups.

Conclusions.  The prevalence of infection was similarly high and increased with age in both populations. In these populations the age of acquisition of H. pylori after 1 year of age does not appear to be a primary factor responsible for the differences in the rates of gastric cancer incidence in adults. Previous findings in adults showed lower prevalence of the most virulent genotypes in Tumaco compared to Pasto, and bacterial virulence may play a key role in determining cancer outcome.
Lower Prevalence of Helicobacter pylori Infection in Patients With Inflammatory Bowel Disease But Not With Chronic Obstructive Pulmonary Disease – Antibiotic Use in the History Does Not Play a Significant Role
Authors: Prónai László , Schandl László , Orosz Zsuzsa , Magyar Pál , Tulassay Zsolt
Published: May 2004

Background.  Patients with inflammatory bowel disease have lower prevalence of Helicobacter pylori infection, but the exact reason for this is not yet clear.

Aim.  To examine whether the antibiotics frequently used in inflammatory bowel disease are responsible for the lower prevalence of H. pylori infection. Patients with chronic obstructive pulmonary disease on prolonged previous antibiotic therapy were used for comparison.

Methods.  Presence/absence of H. pylori infection was detected by a 13C‐urea breath test in 133 patients with inflammatory bowel disease (82 ulcerative colitis, and 51 Crohn's disease) and compared with that of 135 patients with chronic obstructive pulmonary disease and with two age‐matched control groups (200 patients each). Primary disease location, duration of disease and detailed analysis of previous and current medication (dose and duration of antibiotics, steroids, 5‐aminosalicylic acid) were analysed in each cases.

Results.  Seventeen of the 133 patients with inflammatory bowel disease [12.2% (10/82) of ulcerative colitis and 13.7% (7/51) of Crohn's disease] and 90/135 patients with chronic obstructive pulmonary disease (66.7%) were positive for H. pylori. A total of 78/200 (39%) for the inflammatory‐bowel‐disease‐group‐matched controls and 110/210 (55%) for the chronic‐obstructive‐pulmonary‐disease‐matched controls were positive for H. pylori. The history of any antibiotic or steroid therapy had no influence on H. pylori status of patients with inflammatory bowel disease.

Conclusion.  The prevalence of H. pylori compared to the age‐matched controls is significantly lower in patients with inflammatory bowel disease but not in those with chronic obstructive pulmonary disease. Antibiotic use is not responsible for the lower prevalence of H. pylori infection in patients with inflammatory bowel disease.
Serum Antibodies to Helicobacter pylori and its Heat‐Shock Protein 60 Correlate with the Response of Gastric Mucosa‐Associated Lymphoid Tissue Lymphoma to Eradication of H. pylori
Authors: Takenaka Ryuta , Yokota Kenji , Mizuno Motowo , Okada Hiroyuki , Toyokawa Tatsuya , Yamasaki Rie , Yoshino Tadashi , Sugiyama Toshiro , Asaka Masahiro , Shiratori Yasushi , Oguma Keiji
Published: May 2004

Background and aims.  Eradication of Helicobacter pylori leads to regression of mucosa‐associated lymphoid tissue (MALT) lymphomas. In this study, we measured serum antibodies to H. pylori and H. pylori‐recombinant heat‐shock protein 60 (rHSP60) in patients with gastric MALT lymphoma to determine whether humoral immune responses to the bacterial antigens correlate with the efficacy of eradication therapy.

Methods.  Serum samples were obtained from 33 patients with H. pylori‐positive gastric MALT lymphoma before undergoing therapy to eradicate the bacteria. Anti‐H. pylori antibodies were measured in a commercial assay and in immunoassays to lysates and rHSP60 which were prepared from ATCC 43504 strain.

Results.  Helicobacter pylori were eradicated in all 33 patients, and the lymphoma completely regressed histologically in 26 patients (79%). Pre‐treatment titers of serum antibody to H. pylori and to rHSP60 in the patients whose tumor regressed were significantly higher than titers in patients whose tumors did not regress (p = .0011 and .035, respectively). By logistic regression analysis, age (odds ratio = 0.88, 95% confidence interval = 0.80–0.99), endoscopic appearance (0.053, 0.004–0.65), titers of anti‐H. pylori antibodies (67.6, 2.5–1800), and titers of anti‐rHSP60 antibody (6.4, 1.2–36) were identified as significantly associated factors with the outcome of MALT lymphoma.

Conclusions.  Measurement of serum antibodies to H. pylori and HSP60 might be useful for predicting the response of gastric MALT lymphoma to eradication of H. pylori.
Absence of Catalase Reduces Long‐Term Survival of Helicobacter pylori in Macrophage Phagosomes
Authors: Basu Malini , Czinn Steven J. , Blanchard Thomas G.
Published: May 2004

Background.  Some Helicobacter pylori strains can survive within macrophage phagosomes for up to 24 hours. The factors that play a role in this survival remain ill‐defined. Therefore, the contribution of catalase in mediating the survival of H. pylori following phagocytosis was investigated in vitro.

Methods.  An isogenic, catalase‐deficient strain of H. pylori was generated and tested for sensitivity to hydrogen peroxide and susceptibility to macrophage‐mediated killing.

Results.  The isogenic, catalase‐deficient strain of H. pylori was effectively killed by hydrogen peroxide within 3 minutes compared to wild‐type H. pylori which maintained 100% survival up to 21 minutes. The catalase‐deficient mutant was also significantly more susceptible to macrophage‐mediated killing than the parent strain, even when the ratio of bacteria to macrophage was increased.

Conclusion.  These results indicate that although some strains of H. pylori are capable of survival within the macrophage phagosome, survival is dependent on virulence factors such as catalase for evasion of innate host defense.
Long‐Standing Gastric Mucosal Barrier Dysfunction in Helicobacter pylori‐Induced Gastritis in Mongolian Gerbils
Authors: Sun Yi‐Qian , Söderholm Johan D. , Petersson Fredrik , Borch Kurt
Published: May 2004

Background and Aims.  Helicobacter pylori infection causes chronic gastritis and leads to peptic ulcer and gastric adenocarcinoma. An impaired gastric mucosal barrier could be involved in these processes. Our aim was to investigate gastric barrier function in H. pylori‐induced gastritis.

Methods.  Stripped gastric mucosal tissues of H. pylori‐infected Mongolian gerbils (4 weeks and 70 weeks after inoculation, respectively) and controls were mounted in Ussing chambers. 51Cr‐EDTA (paracellular probe) and horseradish peroxidase (HRP, protein antigen) were used to assess mucosal barrier function. The electrophysiological parameters of the mucosa (transepithelial potential, short circuit current, and transepithelial resistance) were monitored as measurements of barrier integrity and viability. Tissue histology was performed to assess inflammation.

Results.  In the antrum, both short‐term gastritis [4.68 (3.88–5.74) × 10−6 vs. control 2.86 (2.34–3.77) × 10−6 cm/s, p < .001] and gastritis of long‐standing [5.72 (3.88–10.94) × 10−6 cm/s, p < .001 vs. control] showed increased permeability to 51Cr‐EDTA. In long‐standing antral gastritis there was also an increased HRP flux [9.01 (2.98–45.02) vs. control 0.52 (0.06–1.20) pmol/h/cm2, p < .001]. In the corpus, permeability to 51Cr‐EDTA was increased only in long‐standing gastritis [4.63 (3.64–7.45) × 10−6 vs. control 2.86 (2.12–3.98) × 10−6 cm/s, p < .01]. Gastric mucosal permeability to 51Cr‐EDTA was correlated to histological inflammation and inflammatory activity. The levels of serum anti‐H. pylori immunoglobulin G were positively correlated to HRP flux and 51Cr‐EDTA permeation.

Conclusions.  Helicobacter pylori‐induced gastritis in Mongolian gerbils was associated with a long‐standing gastric mucosal barrier dysfunction. The barrier defect extended from the antrum into the corpus over time. This impaired barrier function may contribute to perpetuation of chronic inflammation and may be involved in H. pylori‐associated carcinogenesis.
Helicobacter pylori Infection in Turkish Children: Comparison of Diagnostic Tests, Evaluation of Eradication Rate, and Changes in Symptoms after Eradication
Authors: Özçay Figen , Koçak Nurten , Temizel I. N. Saltik , Demir Hülya , Özen Hasan , Yüce Aysel , Gürakan Figen
Published: May 2004

Background.  Helicobacter pylori infection is most frequently acquired in childhood. After this organism is eradicated, the rate of reinfection is low. Thus, it is very important to diagnose and treat the disease appropriately in childhood, and to be able to assess eradication with certainty. Eradication of H. pylori infection is reported to reduce or eliminate abdominal pain and dyspeptic symptoms in children.

Patients and Methods.  The study involved 102 children who had already been diagnosed with symptomatic H. pylori infection based on gastric histopathological examination, urea breath test, rapid urease test, serology and culture. Each patient's symptoms and family history of gastrointestinal problems were recorded. Using histology as the gold standard for identifying H. pylori infection, we determined the diagnostic sensitivity of each of the other methods. Omeprazole or lansoprazole, amoxicillin and clarithromycin were administered as eradication treatment, and each patient was re‐evaluated by urea breath test 8 weeks later. Each child was re‐interviewed about symptoms after treatment. These answers and the results of drug sensitivity testing were recorded. Cases of failed eradication were re‐treated with a quadruple‐drug regimen of tetracycline, metronidazole, bismuth subsalicylate and omeprazole.

Results.  The most frequent symptom was abdominal pain (89.2%). Fifty‐four per cent of the subjects had a family history of dyspeptic symptoms. Sixty‐six patients (64.7%) exhibited nodularity in the antral mucosa. The sensitivities of the diagnostic tests in histologically proven cases were as follows: urea breath test 100%, rapid urease test 89.2%, serology 71.9%, and culture 54.9%. Metronidazole had the highest frequency of resistance (36.4%) and the rate of clarithromycin resistance was 18.2%. The eradication rate after first‐line therapy was 75.5%, and abdominal pain and dyspeptic symptoms were reduced or completely resolved in 75.7% of the successful‐eradication cases. The proportion of failed‐eradication cases that responded well to quadruple‐drug therapy was 93.8%.

Conclusion.  Symptomatic H. pylori infection in a child should always be treated. The urea breath test is an accurate and reliable way to identify H. pylori‐positive patients and to determine the response to treatment. Triple‐agent therapy is effective for eradicating H. pylori infection in children and usually helps reduce or eliminate dyspeptic symptoms. The level of H. pylori resistance to metronidazole is high in our region. The significant rate of resistance to clarithromycin (18.1%) may explain the treatment failure observed in this study.
Temporary Employment, Working Conditions and Expected Exits from Firms
Authors: García‐Serrano Carlos
Published: May 2004

This paper analyses two issues related to working conditions and temporary employment. First, why do temporary workers exhibit lower scores in objective indicators of working life? Second, what is the influence of working conditions on mobility? Using information for Spanish workers, the results indicate that differences in working conditions remain after controlling for individual, job and firm characteristics: in particular, temporary workers with short job tenure seem to occupy jobs with poorer working conditions. Moreover, there is evidence that workers with worse working life are more likely to expect to leave their current firms.
The Impact on Inequality of Raising the Minimum Wage: Gap‐narrowing and Reranking Effects
Authors: Angel‐Urdinola Diego F. , Wodon Quentin
Published: May 2004

Raising the minimum wage may reduce inequality by increasing the wages of low‐skill workers, but it may also increase inequality due to negative impacts on employment that produce wage losses. Using previous estimates of the elasticities of wages and employment to changes in the minimum wage in Colombia and Brazil, we show that the net impact on inequality of increasing the minimum wage may depend on the distributional weights used for inequality measurement. The results are obtained by decomposing the Gini index into reranking and gap‐narrowing effects. Inequality‐increasing reranking effects, which are associated with job losses, may dominate inequality‐decreasing gap‐narrowing effects, which are associated with wage gains, when high weights are placed on workers with low earnings. For standard distributional weights, however, the likely net impact is a reduction in wage inequality.
Conventional glucocorticoid replacement overtreats adult hypopituitary patients with partial ACTH deficiency
Authors: Agha Amar , Liew Aaron , Finucane Francis , Baker Louise , O'Kelly Patrick , Tormey William , Thompson Christopher J.
Published: May 2004

background  Glucocorticoid therapy is associated with potentially serious side‐effects, but there is no information available regarding glucocorticoid requirement in adult hypopituitary patients with partial ACTH deficiency.

subjects  Ten male adult hypopituitary patients with partial ACTH deficiency, baseline plasma cortisol > 200 nmol/l but a peak stimulated cortisol < 500 nmol/l and 10 matched healthy male control volunteers participated.

design  Patients were assigned, in a random order, to a cross‐over protocol of treatment for 1 week with full dose hydrocortisone (10 mg twice daily), half‐dose hydrocortisone (5 mg twice daily), or no treatment. All patients completed all three of the treatment limbs.

measurements  Following each treatment schedule, patients underwent an 11‐h cortisol day curve (CDC), and the results were compared with those from the 10 control volunteers on no glucocorticoid treatment.

results  The integrated CDC values were significantly higher in patients taking a full dose of hydrocortisone compared to controls (P < 0·001). There was no significant difference in the integrated CDC between patients on half‐dose (P = 0·37) or no hydrocortisone treatment (P = 0·13), compared to control subjects. Peak postabsorption cortisol values were higher in patients receiving full‐dose hydrocortisone treatment compared to controls (P < 0·001). There was no significant difference in plasma sodium concentration, blood pressure or corticosteroid‐binding globulin between patients on any treatment schedule and controls.

conclusion  Adult patients with pituitary disease and partial ACTH deficiency have a cortisol secretory pattern comparable to that of healthy controls. Conventional full‐dose replacement with 10 mg twice daily of hydrocortisone produces hypercortisolaemia, whereas half‐dose produces a CDC that is not statistically different from that of healthy controls. The results suggest that current conventional glucocorticoid replacement overtreats patients with partial ACTH deficiency under normal unstressed physiological conditions.
Erythrocyte Na+/K+‐ATPase is increased in subjects with subclinical hypothyroidism
Authors: Nicolini G. , Balzan S. , Colzani R. , Scarlattini M. , Taddei M. C. , Iervasi G.
Published: May 2004

objective  In erythrocytes of patients with overt hyperthyroidism, the number of ouabain‐binding sites and the activity of the Na+/K+‐ATPase have been demonstrated to be decreased, whereas the opposite is true in patients with overt hypothyroidism. No information has been reported on the status of the Na+/K+‐ATPase in subclinically hypothyroid (Sub Hypo) patients.

design  We investigated the number of ouabain‐binding sites and Na+/K+‐ATPase activity in erythrocytes of chronic Sub Hypo subjects.

patients and methods  We measured 3H‐ouabain‐binding sites in erythrocytes from 15 patients with subclinical hypothyroidism, and compared with those found in 17 normal subjects (N), seven with overt hypothyroidism (Hypo) and 10 with overt hyperthyroidism (Hyper). The activity of the sodium pump was assessed by measuring ouabain‐sensitive 86Rb uptake in a subpopulation of the same groups.

results  The number of ouabain‐binding sites in Sub Hypo patients (252 ± 17; mean ± SEM) was significantly higher (P < 0·02) than in Hyper (135 ± 12) and N (203 ± 10) groups, whereas it was not significant different from Hypo (293 ± 31). There was a positive correlation between the number of ouabain‐binding sites and TSH concentrations (P < 0·002) when Sub Hypo and N groups were considered together. There was a negative correlation between the number of ouabain‐binding sites and free thyroxine (FT4; P < 0·0001) and free triiodothyronine (FT3) concentrations (P < 0·001) when all subjects were considered. Ouabain‐sensitive 86Rb uptake (picomoles 86Rb/h 106 cells) in Sub Hypo was significantly higher (4·2 ± 0·5) when compared with N (2·5 ± 0·2, P < 0·01) and Hyper (2·5 ± 0·5, P < 0·02).

conclusions  Erythrocytes of subclinically hypothyroid patients show a significant increase in the number of ouabain‐binding sites and in ouabain‐sensitive 86Rb uptake. The state of erythrocyte Na+/K+‐ATPase may therefore represent a biochemical marker of subclinical hypothyroidism.
Comparison of practical methods for urinary glycosaminoglycans and serum hyaluronan with clinical activity scores in patients with Graves’ ophthalmopathy
Authors: Martins João R. M. , Furlanetto Reinaldo P. , Oliveira Lhoyane M. , Mendes Aline , Passerotti Carlo C. , Chiamolera Maria Izabel , Rocha Antonio J. , Manso Paulo G. , Nader Helena B. , Dietrich Carl P. , Maciel Rui M. B.
Published: May 2004

objective  Immunosuppressive treatment of Graves’ opthalmopathy (GO) should be restricted to patients with active eye disease, but assessing disease activity is difficult. Several methods to evaluate GO activity have been introduced, but none of them is satisfactory. Glycosaminoglycans (GAGs) are complex polysaccharides that participate on the pathogenesis of GO and attempts to correlate its local increase to urinary GAGs (uGAGs) or serum hyaluronan (sHA) have been made, but the available techniques are labourious, time‐consuming and difficult for routine use. The aim of the present study is to develop practical and simple methods for uGAGs and sHA and compare them to the activity and severity of thyroid‐associated ophthalmopathy.

design, patients and measurements  We developed a microelectrophoresis technique for uGAGs and a fluoroassay for sHA and assessed each in 152 patients with Graves’ disease, 25 without GO and 127 with GO, classified according to the Clinical Activity Score (CAS). All patients had been euthyroid for > 2 months.

results  Patients with inactive disease (CAS = 2, n = 100) had uGAGs (4·2 ± 1·3 µg/mg/creatinine) and sHA (11·1 ± 7·2 µg/l) that did not differ from normal subjects (3·1 ± 1·1 µg/mg/creatinine, n = 138 and 13·9 ± 9·6 µg/l, n = 395). In contrast, patients with active eye disease (CAS = 3, n = 27) had uGAGs (8·4 ± 2·7 µg/mg/creatinine) and sHA (32·3 ± 17·8 µg/l) 2–3 times higher than those patients with inactive eye disease. Using a cut‐off of 6·1 µg/mg creatinine for uGAGs and 20·7 µg/l for sHA we found, respectively, 85% and 81% sensitivity and 93% and 91% specificity for each test. The positive and negative predictive values were 77% and 96% for uGAGs and 71% and 95% for sHA.

conclusion  Employing these two new methods we have established a significant relationship between the levels of uGAGs and/or sHA and the clinical activity of GO. Therefore, together with CAS, uGAGs determination, and, to a lesser degree, sHA, would be very useful in the discrimination from active and inactive ocular disease and aid in deciding on the best therapy for GO patients.
Profound amplification of secretory‐burst mass and anomalous regularity of ACTH secretory process in patients with Nelson's syndrome compared with Cushing's disease
Authors: Van Aken Maarten O. , Pereira Alberto M. , Van Den Berg Gerrit , Romijn Johannes A. , Veldhuis Johannes D. , Roelfsema Ferdinand
Published: May 2004

objective  As described originally, Nelson's syndrome is characterized by grossly elevated ACTH concentrations, a sellar mass and skin hyperpigmentation emerging in the course of Cushing's disease after bilateral adrenalectomy. No detailed studies have defined whether the mechanisms directing ACTH secretion differ in Nelson's syndrome and untreated Cushing's disease.

patients and methods  To address this pathophysiological issue, we studied nine patients fulfilling the criteria of Nelson's syndrome receiving glucocorticoid and mineralocorticoid replacement; nine patients with untreated pituitary‐dependent Cushing's disease and nine gender‐ and age‐matched controls. ACTH release was appraised by monitoring plasma ACTH concentrations in blood samples collected every 10 min for 24 h. ACTH secretion rates and endogenous decay were quantified by multiparameter deconvolution analysis. The orderliness of the ACTH release process was delineated by the approximate entropy (ApEn) statistic. Diurnal variation in ACTH secretion was appraised by cosinor analysis.

results  Basal ACTH secretion was increased sixfold and pulsatile secretion ninefold in patients with Nelson's syndrome compared with Cushing's disease (P ≤ 0·01 and P ≤ 0·001, respectively). The increase in pulsatile secretion was due to an eightfold augmentation of burst mass. Event frequency was comparable in both patient groups (32 ± 1 vs. 28 ± 2 pulses/24 h), and higher than in normal controls (22 ± 1 pulses/24 h, P < 0·0001). Paradoxically, the consistency of subordinate patterns of serial ACTH release, albeit disrupted in active Cushing's disease, was normal in Nelson's syndrome (P = 0·014). Normal ACTH secretory‐process regularity in Nelson's syndrome was attributable to a more reproducible (lower ApEn) succession of ACTH secretory‐burst mass denoting more uniform amplitude evolution over 24 h (P = 0·007, Nelson vs. Cushing). However, the quantifiable regularity of serial interburst intervals (waiting times) was unexpectedly elevated in Nelson's syndrome (P = 0·022). Nelson patients maintained a significant diurnal rhythm in ACTH release, which was marked by a 15‐fold greater amplitude (P = 0·0018 vs. Cushing’s) and a 4‐h acrophase (maximum) delay (P = 0·037 vs. control).

conclusion  The present detailed analyses delineate marked ACTH secretory‐burst mass amplification and (amplitude‐independent) anomalous regularity of successive pulse size and timing in Nelson's syndrome compared with Cushing's disease or controls. We postulate that the foregoing novel distinctions are due to unique tumoural secretory properties, concurrently required glucocorticoid replacement and/or hypothalamic injury associated with prior radiotherapy in Nelson's syndrome.
Allelopathic potential of Lolium rigidum Gaud. on the early growth of three associated pasture species
Authors: San Emeterio L. , Arroyo A. , Canals R. M.
Published: May 2004

In Mediterranean areas, the establishment of multi‐species pastures for extensive livestock use is an alternative to the growing of traditional cereal crops. Lolium rigidum Gaud. is one of the most valuable forage grasses adapted to semiarid environments but its performance in mixtures is not fully understood. Field observations suggest that the species exerts allelopathic effects, although there is no evidence in the literature to support this assumption. The objective of the study was to determine whether L. rigidum affects the germination and seedling growth of common forage species by allelopathic means. Two bioassays were conducted to test for the allelopathic potential of seeds and adult (shoot and root) tissues of L. rigidum on two grasses, Lolium multiflorum Lam. and Dactylis glomerata L., and a legume, Medicago sativa L. The three species showed different degrees of sensitivity to L. rigidum with L. multiflorum being particularly sensitive to allelopathy. Positive and negative effects of L. rigidum on seedling development were noted. Shoot extracts of L. rigidum displayed the most consistent negative effects by inhibiting elongation of the radicle of the three target species. The significance of the results is that in drought‐prone environments and where water resources are scarce poor root development decreases the ability of the plants to grow and survive.