bluuebunny/crossref_metadata_2025 huggingface dataset:
A Proposed Mechanism for the Inhibitory Effects of Oxidative Stress on Rubisco Assembly and Its Subunit Expression
Authors: Cohen Idan , Knopf Joel A. , Irihimovitch Vered , Shapira Michal
Published: January 2005

In Chlamydomonas reinhardtii, a light-induced oxidative stress shifts the glutathione pool toward its oxidized form, resulting in a translational arrest of the large subunit (LSU) of Rubisco. We show here that the translational arrest of LSU is tightly coordinated with cessation of Rubisco assembly, and both processes take place after a threshold level of reactive oxygen species is reached. As a result, the small subunit is also eliminated by rapid degradation. We previously showed that the amino terminus of the LSU could bind RNA in a sequence-independent manner, as it shares a structural similarity with the RNA recognition motif. This domain becomes exposed only under oxidizing conditions, thus restricting the RNA-binding activity. Here we show that in vitro, thiol groups of both subunits become oxidized in the presence of oxidized glutathione. The structural changes are mediated by oxidized glutathione, whereas only very high concentrations of H2O2 confer similar results in vitro. Changes in the redox state of the LSU thiol groups are also observed in vivo, in response to a physiological light shock caused by transfer of cells from low light to high light. We propose that during a photooxidative stress, oxidation of thiol groups occurs already in nascent LSU chains, perhaps hindering their association with chaperones. As a result, their RNA recognition motif domain becomes exposed and will bind any RNA in its vicinity, including its own transcript. Due to this binding the ribosome stalls, preventing the assembly of additional ribosomes on the transcript. Polysome analysis using Suc gradients indeed shows that the rbcL RNA is associated with the polysomal fraction at all times but shifts toward fractions that contain smaller polysomes and monosomes during oxidative stress. Thus, translational arrest of the LSU most likely occurs at a postinitiation stage.
Lymphocyte telomere dynamics and telomerase activity in inflammatory bowel disease: effect of drugs and smoking
Authors: Getliffe K. M. , Al Dulaimi D. , Martin‐Ruiz C. , Holder R. L. , Von Zglinicki T. , Morris A. , Nwokolo C. U.
Published: January 2005

Background : The chromosome instability observed in peripheral blood lymphocytes in ulcerative colitis could be a biomarker of cancer susceptibility.

Aim : To determine whether accelerated telomere shortening could explain chromosome instability and assess the effect of drugs and smoking on telomere dynamics in these cells.

Methods : Peripheral blood lymphocytes were isolated from ulcerative colitis, Crohn's disease and non‐inflammatory bowel disease control patients. Telomere lengths were measured by quantitative real‐time polymerase chain reaction. After activation and cell separation, telomerase activity and human telomerase reverse transcriptase messenger ribonucleic acid were measured by telomerase repeat amplification protocol enzyme‐linked immunosorbent serological assay and quantitative real‐time polymerase chain reaction, respectively.

Results : Age‐related telomere loss in peripheral blood lymphocytes was similar in ulcerative colitis, Crohn's disease and control patients. Telomerase activity decreased with age in all groups and correlated positively with telomere length (r = 0.489, P =0.006). Among Crohn's disease patients, azathioprine was associated with decreased telomerase activity (0.66 vs. 1.54, P = 0.026, P < 0.05) and smoking was associated with decreased human telomerase reverse transcriptase mRNA expression (10.5 vs. 33.3, P =0.036, P < 0.05).

Conclusions : Telomere shortening is not accelerated and therefore cannot be the cause of the chromosome instability observed in ulcerative colitis peripheral blood lymphocytes. Azathioprine and cigarette smoking modify telomerase expression in these cells.
Functional symptoms in inflammatory bowel disease and their potential influence in misclassification of clinical status
Authors: Barratt H. S. , Kalantzis C. , Polymeros D. , Forbes A.
Published: January 2005

Background : Functional symptoms occur in inflammatory bowel disease probably more than in the general population. Existing disease indices rely heavily on symptoms that may be organic or functional. This may explain inconsistencies between recent therapeutic trials in inflammatory bowel disease. Clinically, misinterpretation can lead to over‐treatment of functional symptoms with potent agents, and to under‐treatment of inflammatory bowel disease when inflammatory features are more subtle.

Aim : To assess functional symptoms in inflammatory bowel disease and to devise simple means of their evaluation.

Methods : Patients with Crohn's disease, ulcerative colitis, and irritable bowel syndrome completed questionnaires, generating inflammatory bowel disease and irritable bowel syndrome indices. Data from outliers selected as exemplars were employed to create a new index.

Results : One hundred and ninety patients completed questionnaires. Overall, Crohn's and irritable bowel syndrome patients had similar functional features. The new scoring system was based on the eight apparently discriminant symptoms. Prospective evaluation in a separate cohort of 180 inflammatory bowel disease patients yielded scores that are independent of established indices, inflammatory markers and psychometric scores.

Conclusions : Patients with Crohn's report comparable rates of apparently functional symptoms to those with irritable bowel syndrome. A new score has been developed to help in their identification. This has the potential to guide therapeutic decisions and optimize future trial recruitment.
In vivo evaluation of a colonic delivery system using isotope techniques
Authors: Verbeke K. , de Preter V. , Geboes K. , Daems T. , van den Mooter G. , Evenepoel P. , Rutgeerts P.
Published: January 2005

Aim:  To evaluate, using isotope techniques, the in vivo effectiveness of a pH‐dependent colonic delivery system.

Methods:  In order to dispose of differently labelled substrates for measurement of orocaecal transit time, inulin‐14C‐carboxylic acid was evaluated as an alternative substrate to inulin and lactose‐13C‐ureide. Secondly, the time of release of 13C‐ and 15N‐urea from the colonic delivery system was compared with the orocaecal transit time, measured using inulin and inulin‐14C‐carboxylic acid. This study was repeated after a 2‐week lactulose intake period.

Results:  The orocaecal transit time determined using inulin‐14C‐carboxylic acid (398 min) was not significantly different from the orocaecal transit time determined using inulin (420 min) or lactose‐13C‐ureide (396 min). Before lactulose intake, the 13CO2 excretion time was 358 min and the orocaecal transit times determined with the inulin‐14C‐carboxylic acid and inulin breath test were 376 and 375 min respectively. After lactulose, the 13CO2 excretion time was 383 min and orocaecal transit times were 354 min for inulin‐14C‐carboxylic acid and 392 min for inulin. A highly significant correlation was found. Good agreement was found between the urinary 15N excretion and the appearance of 13CO2 in breath.

Conclusion:  Isotope techniques provide an excellent non‐invasive tool for the in vivo evaluation of a colonic delivery system.
Factors associated with adolescent abortion in a rural area of Bangladesh
Authors: Kapil Ahmed M. , Van Ginneken Jeroen , Razzaque Abdur
Published: January 2005

This study examines levels and trends in abortion among adolescent girls in 1982–98 and identifies groups of adolescents who are at high risk for having an abortion. The study used data sets collected in Matlab in Bangladesh where the Center for Health and Population Research at ICDDR,B, has maintained a demographic surveillance system, since 1966. Both bivariate and multivariate techniques of analysis were employed. We also used qualitative information derived from in‐depth interviews with adolescents. The incidence of abortion was 35 times higher for unmarried than for married adolescents. Abortion ratios were also higher for adolescents who were <18 years old and for those with more than primary education. A little less than half of the abortions were induced by biomedical health workers (by means of menstrual regulation) which means that traditional providers fulfilled an important function in this rural area. The findings suggest that high‐quality abortion services provided to adolescents in the framework of comprehensive reproductive health services will help to lower abortions in general and of unsafe abortions provided by traditional providers in particular.
Efficacy and effectiveness of the combination of sulfadoxine/pyrimethamine and a 3‐day course of artesunate for the treatment of uncomplicated falciparum malaria in a refugee settlement in Zambia
Authors: Depoortere Evelyn , Guthmann Jean‐Paul , Pressé Jacinthe , Sipilanyambe Naawa , Nkandu Esther , Balkan Suna , De Pécoulas Philippe Eldin , Legros Dominique
Published: January 2005

In the Maheba Refugee Settlement, in the clinics supported by Médecins Sans Frontières, all children aged up to 5 years with a confirmed diagnosis of uncomplicated falciparum malaria are treated with the combination of sulfadoxine/pyrimethamine (SP) and artesunate (AS). We compared the treatment's efficacy and effectiveness. Patients were randomized in order to receive the treatment supervised (efficacy) or unsupervised (effectiveness). Therapeutic response was determined after 28 days of follow up. The difference between recrudescence and re‐infection was ascertained by polymerase chain reaction (PCR). We also assessed genetic markers associated to SP resistance (dhfr and dhps). Eighty‐five patients received treatment under supervision and 84 received it unsupervised. On day 28, and after PCR adjustment, efficacy was found to be 83.5% (95% CI: 74.1–90.5), and effectiveness 63.4% (95% CI: 52.6–73.3) (P < 0.01). Point mutations on dhfr (108) and dhps (437) were found for 92.0% and 44.2% respectively of the PCR samples analysed. The significant difference in therapeutic response after supervised and unsupervised treatment intake can only be explained by insufficient patient adherence. When implementing new malaria treatment policies, serious investment in ensuring patient adherence is essential to ascertain the effectiveness of the new treatment schedules.
How do patients use antimalarial drugs? A review of the evidence
Authors: Yeung Shunmay , White Nicholas J.
Published: January 2005

Patient adherence is a major determinant of the therapeutic response to antimalarial drugs, as most treatments are taken at home without medical supervision. With the introduction of new, effective, but more expensive antimalarials, there is concern that the high levels of efficacy observed in clinical trials may not be translated into effectiveness in the normal context of use. We reviewed available published evidence on adherence to antimalarial drugs and community drug usage; 24 studies were identified of which nine were ‘intervention’ studies, seven were classified as ‘outcome studies’, and the remainder were purely descriptive studies of antimalarial adherence. Definitions, methods, and results varied widely. Adherence was generally better when treatments were effective, and was improved by interventions focusing on provider knowledge and behaviour, packaging, and provision of correct dosages. There is insufficient information on this important subject, and current data certainly do not justify extrapolation from results with ineffective drugs to new effective treatments. Research in this area would benefit from of standardization of methodologies and the application of pharmacokinetic modelling.
Substantial increase of malaria in inland areas of eastern French Guiana
Authors: Carme Bernard
Published: January 2005

This study includes malaria cases diagnosed by the Parasitology Unit of the Cayenne Hospital (French Guiana) using the same procedure from 1996 to 2003. We provide data for two main rural communities in slightly inland areas of eastern French Guiana (Cacao, Régina) and for Cayenne, the capital of this French department. The frequency of bouts of malaria has been increasing rapidly since mid‐2001, in these regions that were virtually considered to be malaria‐free. This substantial increase of malaria appears mainly to involve Plasmodium vivax and recent Brazilian immigrants. Other plausible explanations which could account for the observed trend are discussed.
Evidence basis for antimalarial policy change in Sierra Leone: five in vivo efficacy studies of chloroquine, sulphadoxine–pyrimethamine and amodiaquine
Authors: Checchi Francesco , Roddy Paul , Kamara Sarian , Williams Arthur , Morineau Guy , Wurie Abdul Rahman , Hora Bona , Lamotte Nadine de , Baerwaldt Tim , Heinzelmann Annette , Danks Alison , Pinoges Loretxu , Oloo Aggrey , Durand Rémy , Ranford‐Cartwright Lisa , de Smet Martin ,   on behalf of the Sierra Leone Antimalarial Efficacy Study Collaboration
Published: January 2005

Objectives  To provide nationally relevant information on the antimalarial efficacy of chloroquine (CQ), sulphadoxine–pyrimethamine (SP) and amodiaquine (AQ) in Sierra Leone, with a view to updating antimalarial policy in the country.

Methods  Between October 2002 and May 2003, standard WHO methodology for in vivo efficacy assessment was used in five sites to study the therapeutic response of 6–59 months old uncomplicated Plasmodium falciparum malaria cases treated with CQ (n = 247), SP (n = 353) or AQ (n = 434). Follow‐up was of 28 days, with polymerase chain reaction genotyping to distinguish late recrudescences from re‐infections.

Results  Overall 85.3% of patients reached an analysable endpoint. CQ failure proportions were very high, ranging from 39.5% (95% CI: 25.0–55.6) in Kabala to 78.8% (65.3–88.9) in Kailahun. Early failures under CQ were frequent. SP efficacy was also disappointing, with failure from 23.2% (13.9–34.9) in Kabala to 46.1% (35.4–57.0) in Kailahun. AQ resistance was more moderate, ranging from 5.4% (1.8–12.1) in Makeni to 29.8% (20.3–40.8) in Kailahun, with almost no early failures. AQ also provided more rapid fever and parasite clearance.

Conclusion  In a consensus meeting organized by the Ministry of Health and Sanitation, and based on these findings, artesunate (AS) + AQ and artemether–lumefantrine (Coartem™) were identified as the only options to rapidly replace CQ. The choice fell on AS + AQ because of expected high efficacy, lower cost in a blister presentation, and the absence of safety data on artemether–lumefantrine in pregnancy. Donor support is required to support this policy change. Throughout Africa, as SP resistance increases, these two regimens are probably the only options available while newer combinations are developed. Efficacy studies should focus on testing AQ and AS + AQ.
Topical quinolone vs. antiseptic for treating chronic suppurative otitis media: a randomized controlled trial
Authors: Macfadyen Carolyn , Gamble Carrol , Garner Paul , Macharia Isaac , Mackenzie Ian , Mugwe Peter , Oburra Herbert , Otwombe Kennedy , Taylor Stephen , Williamson Paula
Published: January 2005

Objective  To compare a topical quinolone antibiotic (ciprofloxacin) with a cheaper topical antiseptic (boric acid) for treating chronic suppurative otitis media in children.

Design  Randomized controlled trial.

Setting and participants  A total of 427 children with chronic suppurative otitis media enrolled from 141 schools following screening of 39 841 schoolchildren in Kenya.

Intervention  Topical ciprofloxacin (n = 216) or boric acid in alcohol (n = 211); child‐to‐child treatment twice daily for 2 weeks.

Main outcome measures  Resolution of discharge (at 2 weeks for primary outcome), healing of the tympanic membrane, and change in hearing threshold from baseline, all at 2 and 4 weeks.

Results  At 2 weeks, discharge was resolved in 123 of 207 (59%) children given ciprofloxacin, and in 65 of 204 (32%) given boric acid (relative risk 1.86; 95% CI 1.48–2.35; P < 0.0001). This effect was also significant at 4 weeks, and ciprofloxacin was associated with better hearing at both visits. No difference with respect to tympanic membrane healing was detected. There were significantly fewer adverse events of ear pain, irritation, and bleeding on mopping with ciprofloxacin than boric acid.

Conclusions  Ciprofloxacin performed better than boric acid and alcohol for treating chronic suppurative otitis media in children in Kenya.
Itinéraire thérapeutique des malades indigents au Bénin (Pauvreté et soins de santé)
Authors: Ouendo Edgard‐Marius , Makoutodé Michel , Paraiso Moussiliou N. , Wilmet‐Dramaix Michèle , Dujardin Bruno
Published: January 2005

Resumé

Dans un système de soins payants, il y a un risque de marginaliser les pauvres. L'Initiative de Bamako suggère que des dispositions soient prises pour éviter les exclusions. Donc les itinéraires thérapeutiques ne devraient plus dépendre de la capacitééconomique.

Objectif  L'objectif de l’étude est d‘identifier les étapes de l'itinéraire thérapeutique des indigents et non indigents en cas de maladie.

Méthodes  Il s'agit une étude prospective de 12 mois. Seize sites ont été sélectionnés aléatoirement après une division en quatre strates du Bénin. L’échantillon est constitué de 1312 mènages (668 indigents, 644 non indigents) pour un total de 9554 personnes. Ceux qui ont été malade pendant la période d’étude ont èté interviewés sur l'itinéraire thérapeutique adopté.

Résultats  Sur les 9554 personnes de notre échantillon, 1959 (20,5%) dont 1091 indigents ont été malades au moins une fois. Au 1er recours, les indigents utilisent moins les centres de santé que les non indigents (20%vs. 26,3%; P < 0,001). Mais l'automédication moderne et traditionnelle sont les recours les plus utilisés par la majorité (66,4% chez les indigents et 63,9% chez les non indigents). A l'intérieur des strates (régions), une différence se note au 1er recours entre les choix des indigents et non indigents dans les régions urbaine et nord (P < 0,001). Quel que soit le type de 1er recours utilisé, il n'existe pas de différence statistiquement significative entre la satisfaction thérapeutique des indigents et des non indigents. Les malades non satisfaits au 1er recours sont surtout ceux qui ont utilisé l'automédication traditionnelle et moderne. Malgré cela, au 2 recours l'automédication moderne et traditionnelle restent encore les recours privilégiés et ces choix sont semblables chez indigents et non indigents.

Conclusion  L’étude met l'accent sur les différences entre indigents et non indigents dans l'itinéraire thérapeutique. Le premier recours étant l’étape clé où on note des diffèrences.
Ole e 2 and Ole e 10: new clinical aspects and genetic restrictions in olive pollen allergy
Authors: Quiralte J. , Llanes E. , Barral P. , Arias de Saavedra J. M. , Sáenz de San Pedro B. , Villalba M. , Florido J. F. , Rodríguez R. , Lahoz C. , Cárdaba B.
Published: January 2005

Background:  The clinical characteristics in olive pollen allergy are dependent on the antigenic load, the allergens profile, and the genetic restrictions. Our objective was to determine specific response pattern in Ole e 2 and Ole e 10 sensitization at those levels.

Methods:  We studied 146 patients with seasonal rhinitis and/or asthma and positive prick test to Olea europaea pollen. IgE against Ole e 2 and Ole e 10 were detected by skin prick test and ELISA. HLA‐DRB1 and HLA‐DQB1 loci were typed by polymerase chain reaction sequence‐specific primers method.

Results:  A total of 102 (69.9%) and 79 (54.0%) patients showed significant IgE antibody response against Ole e 2 and Ole e 10, respectively. There was a significant association between Ole e 2 (OR 2.2, P = 0.04) and Ole e 10 reactivities (OR 2.8, P = 0.007) with asthma. In addition, total and specific IgE antibody levels significantly correlated with asthma (P < 0.05). Patients who reacted to both allergens reached the highest asthma risk factor (OR 4.3, P = 0.002). Phenotypic frequency of DR7 (OR 5.4, Pc = 0.003) and DQ2 (OR 3.6, Pc = 0.02) were increased in positive Ole e 2 patients compared with control subjects. DR2(15) phenotypic frequency was significantly increased (OR 5.6, Pc = 0.02) in positive Ole e 10 patients compared with control subjects.

Conclusions:  Our data suggest an association of Ole e 2 and Ole e 10 with bronchial asthma. Also, we found a genetic control of Ole e 2 and Ole e 10 IgE‐specific responses that could be relevant to clinical disease in olive pollen allergy.
cDNA cloning and immunologic characterization of a novel EF‐1β allergen from Penicillium citrinum
Authors: Tang R.‐B. , Chen Y.‐S. , Chou H. , Lee S.‐S. , Tai H.‐Y. , Shen H.‐D.
Published: January 2005

Background:  We have identified previously that Penicillium citrinum is the most prevalent Penicillium species in the Taipei area. It is important to delineate the whole spectrum of allergenic components of this prevalent airborne fungus. The purpose of this study was to identify novel P. citrinum allergens through molecular cloning of allergen genes using a cDNA library of P. citrinum and sera from patients with bronchial asthma.

Methods:  A lambda‐Uni‐ZAP XR‐based cDNA library of P. citrinum was screened with sera from asthmatic patients. An IgE‐binding cDNA clone was isolated and heterologously expressed in Escherichia coli. The frequency of IgE‐binding to the expressed protein and the IgE reactivity to allergen subunits were analyzed by immunoblotting.

Results:  An IgE‐reactive cDNA clone (clone B) was isolated by plaque immunoassay. The cDNA insert is 876‐bp long and encodes a 228‐amino acid polypeptide with a calculated molecular mass of 25 035 Da. Protein database search with the deduced clone B sequence revealed that 121 (53%) and 82 (36%) of the 228 amino acids were identical to those of the elongation factor 1‐beta (EF‐1β) proteins from the yeast Saccharomyces cerevisiae and the parasite Echinococcus granulosus, respectively. His‐tagged recombinant clone B proteins were constructed and expressed in E. coli. Seven (8%) of the 92 serum samples from patients with bronchial asthma showed IgE‐binding to the recombinant clone B protein. Among these seven positive sera, five demonstrated IgE‐binding to the C‐terminal fragment (aa 119–228) while the other two sera showed IgE reactivity to the N‐terminal fragment (aa 1–118) of this newly identified EF‐1βPenicillium allergen.

Conclusions:  A novel P. citrinum allergen (Pen c 24) was identified and characterized in the present study. Results obtained provide more information about allergens of prevalent airborne fungi and a basis to understand more about the IgE responses in human atopic disorders and in parasitic infections.
Dendritic cells and the regulation of the allergic immune response
Authors: Lambrecht B. N.
Published: January 2005

Studies in mouse models of asthma have revealed a critical role for airway dendritic cells in the induction of Th2 sensitization to inhaled allergens. Under some conditions, subsets of dendritic cells can also induce tolerance or Th1 responses to the same allergens, depending on the context in which the antigen is seen. This article discusses various aspects of DC biology as it relates to allergic sensitization and also provides a summary of the recent evidence that dendritic cells function beyond sensitization.
Skin reactivity to aeroallergens is reduced in human T‐lymphotropic virus type I‐infected healthy blood‐donors (asymptomatic carriers)
Authors: Souza‐Machado A. , Galvão T. S. , Porto A. , Figueiredo J. , Cruz Á. A.
Published: January 2005

Background:  A type 2 immune response, characterized by high levels of interleukin‐4 and immunoglobulin E synthesis is a hallmark of respiratory allergic diseases. Individuals infected with human T‐lymphotropic virus type I (HTLV‐I) virus have spontaneous T‐cell proliferation and increased interferon γ production, which are immunological functions associated with a type 1 immune response.

Objective:  To determine the frequency of asthma and rhinitis symptoms and immediate skin reactivity to aeroallergens in HTLV‐I infected individuals, compared with noninfected subjects.

Methods:  Cross sectional study of 101 HTLV‐I infected and 101 control uninfected blood donors, assessed by enzyme‐linked immunosorbent assay and Western blot assays. The subjects were age and sex‐matched, identified as presenting allergy history by questionnaire, which was complemented by a complete clinical examination and skin prick tests for aeroallergens.

Results:  The frequency of atopy was lower in infected than uninfected subjects, 14.9 and 29.7% (P = 0.017), respectively. Skin reactivity to Dermatophagoides pteronissynus, Dermatophagoides farinae and Blomia tropicalis were the most frequently observed among all the tested antigens in both groups. Skin reactivity to histamine was also reduced in the infected individuals compared with uninfected subjects (medians 4.0 vs 5.0, respectively; P < 0.0001). Infection by HTLV‐I was found to be a factor of protection to atopy (RP 0.44; P = 0.005).

Conclusions:  The HTLV‐I infection reduces the frequency of respiratory allergy and skin reactivity to aeroallergens.
Rhinitis is an independent risk factor for developing cough apart from colds among adults
Authors: Guerra S. , Sherrill D. L. , Baldacci S. , Carrozzi L. , Pistelli F. , Di Pede F. , Viegi G.
Published: January 2005

Background:  In cross‐sectional clinical studies, rhinitis has been shown to be strongly associated with co‐existing chronic cough. However, to date, this association has been poorly delineated from a prospective and epidemiological standpoint.

Methods:  We used data from the ‘Pisa Prospective Study’, a population‐based longitudinal cohort study composed of a baseline and a follow‐up survey taken approximately 5 years apart from each other. Information on cough, rhinitis, and other risk factors was collected by standardized questionnaire. Cough apart from colds was defined as either ‘chronic’ (most days for at least 3 months for at least two consecutive years) or ‘occasional’ (if the three above temporal conditions were not met). ‘Any’ cough was defined as the presence of either occasional or chronic cough.

Results:  Complete information was available for 1670 subjects who were ≥15 years old and had no positive history of cough apart from colds at the baseline survey. Among them, 299 (18%) had rhinitis at baseline. By the follow‐up survey, 16% of the subjects with rhinitis had developed any cough apart from colds, as compared with only 10% of the subjects without rhinitis (OR 1.7, 95% CI 1.2–2.5, P < 0.005). After adjustment for age, gender, asthma status, smoking, and occupational exposure, rhinitis remained significantly associated with an increased risk both for any cough (OR 1.8, 95% CI 1.2–2.6) and for occasional and chronic cough separately (OR 2.2, 95% CI 1.1–4.5, and OR 1.7, 95% CI 1.1–2.6, respectively).

Conclusions:  Rhinitis is a significant and independent risk factor for developing cough among adults. Further research is needed to assess potential implications in terms of prevention.
CD4+IL‐13+ cells in peripheral blood well correlates with the severity of atopic dermatitis in children
Authors: La Grutta S. , Richiusa P. , Pizzolanti G. , Mattina A. , Pajno G. B. , Citarrella R. , Passalacqua G. , Giordano C.
Published: January 2005

Background:  In atopic dermatitis (AD) a Th1/Th2 imbalance has been reported, and interleukin (IL)‐13 seems to play a pivotal role in the inflammatory network. We tried to assess the correlation between the immunological marker CD4+IL‐13+ and the clinical phase of extrinsic AD in children.

Methods:  Twenty children with AD were studied. Assessed parameters were: clinical severity (SCORAD index), total serum immunoglobulin E (IgE), blood eosinophil count, and percentage of CD4+IFNγ+, CD4+IL‐4+, CD4+IL‐13+ T cells. Determinations were carried out in the acute phase and after clinical remission were achieved. Ten nonatopic‐matched children served as controls.

Results:  At baseline, AD was mild in 25%, moderate in 50% and severe in 25% of children. In the acute phase a significant relationship between the eosinophil count and the SCORAD index was found (P = 0.0001). Blood CD4+IL‐4+ were significantly higher in the AD group (median 17.0, range: 13.7–21.4) than in controls (12.6, 6.4–17.2, P < 0.0001). CD4+IL‐13+ cells in the AD group well correlated (P = 0.0007) with SCORAD index. At remission, a significant correlation between SCORAD index and eosinophil count was found (P < 0.03) and the percentage of CD4+IL‐13+ cells globally decreased (P < 0.0001), while no difference was found among SCORAD classes.

Conclusion:  This study confirms the Th2 profile predominance in the peripheral blood of children with AD, and evidences close relationship between the number of CD4+IL‐13+ T cells and the disease's severity.
Birth‐related increase in intracolonic hydrogen gas and nitric oxide as indicator of host–microbial interactions
Authors: Sobko T. , Norman M. , Norin E. , Gustafsson L. E. , Lundberg J. O.
Published: January 2005

Background:  Bacterial colonization of the intestine early in life might have implications for allergy development. We studied early host–bacterial interactions in the gut by simultaneous measurements of hydrogen gas (H2) and faecal short chain fatty acid pattern (SCFAs), i.e. bacterial products, as well as of nitric oxide (NO), a marker of mucosal immune activation.

Methods:  A novel minimally invasive technique was used for repeated measurements of luminal colonic H2 and NO in 32 healthy newborn infants delivered vaginally or by Caesarean section. Luminal gas was sampled and analysed at five occasions: immediately after birth, day 1, days 3–5, 1 and 5–6 months after birth.

Results:  Colonic H2, NO and faecal SCFAs were undetectable at birth. The H2 and SCFAs appeared within 24 h and continued to increase during the 6 months follow‐up. Nitric oxide remained very low until 3–5 days after birth at which time it markedly increased. In some apparently healthy infants NO transiently reached levels similar to those seen in adults with inflammatory bowel disease.

Conclusion:  Intracolonic measurements of H2 and NO may be useful to monitor the developmental colonization process as well as mucosal responses.
IgE, IgG1, and IgG4 antibody responses to Blomia tropicalis in atopic patients
Authors: Pereira E. A. L. , Silva D. A. O. , Cunha‐Júnior J. P. , Almeida K. C. , Alves R. , Sung S. J. , Taketomi E. A.
Published: January 2005

Background:  Allergens from house dust mites (HDMs), Dermatophagoides pteronyssinus and Blomia tropicalis are clinically relevant in atopic respiratory diseases in tropical countries.

Aims of the study:  To evaluate immunoglobulin (Ig)E, IgG1, and IgG4 antibody responses to B. tropicalis in Brazilian atopic patients.

Methods:  About 110 patients with allergic rhinitis with/without asthma and 33 control subjects underwent skin prick testing (SPT) with HDM extracts, and their sera were tested for IgE and IgG subclass antibodies to D. pteronyssinus and B. tropicalis by enzyme‐linked immunosorbent assay (ELISA) and immunoblotting.

Results:  Most patients (56%) had positive SPT to B. tropicalis extract (B. tropicalis+ group), although 51% were reactive to both B. tropicalis and D. pteronyssinus and 6% were sensitized to B. tropicalis only. IgE‐ELISA detected 43%B. tropicalis positivity with high‐specific IgE levels in B. tropicalis+ patients. Specific IgG4 levels were higher in B. tropicalis+ than B. tropicalis− groups and correlated with specific IgE levels. The IgG1 levels to B. tropicalis were higher in patients than controls. The major allergenic B. tropicalis components recognized by B. tropicalis+ patient sera were the 54, 66, and 68 kDa proteins. The IgG4‐binding protein profiles closely resembled that of IgE. The IgG1 antibodies recognizing multiple B. tropicalis protein species were detected in sera of all three patient groups.

Conclusions:  A large percentage of our allergic patients are B. tropicalis+. They are more frequently sensitized to high‐molecular weight (HMW) B. tropicalis components than the major low‐molecular weight (11–15 kDa) allergens detected in other studies. The results suggest that HMW B. tropicalis antigenic components are potential candidates for evaluating allergen exposure and sensitization, and for immunotherapy treatment.
Intravenous immunoglobulin replacement prevents severe and lower respiratory tract infections, but not upper respiratory tract and non‐respiratory infections in common variable immune deficiency
Authors: Favre O. , Leimgruber A. , Nicole A. , Spertini F.
Published: January 2005

Background:  Although the dose of 400 mg/kg body weight intravenous immunoglobulins (IVIG) every 3–4 weeks is now standard for treating patients with common variable immune deficiency, studies demonstrating its long‐term benefits over low 200 mg/kg dose and its effects on infectious subsets (upper vs lower respiratory vs non‐respiratory infections) are rare.

Methods:  All patients from a single center with the diagnosis of common variable immune deficiency and whose clinical chart was available during three successive therapeutic periods [a pre‐IVIG replacement period, a low‐dose (200 mg/kg every 3 weeks) and a standard‐dose replacement period (400 mg/kg every 3 weeks)] were screened retrospectively.

Results:  Seven patients followed up for a total of 116 patient‐years over the three defined periods of observation were recruited. When compared with low‐dose therapy, standard‐dose intravenous immunoglobulin therapy raised trough IgG levels from 4.3 to 6.5 g/l and significantly decreased the overall frequency of infections, with marked effects on lower respiratory tract and severe infection number. In contrast, non‐respiratory and upper respiratory infections were, in comparison, resistant to therapy.

Conclusions:  Overall, these data support the use of standard‐dose 400 mg/kg intravenous immunoglobulin therapy, despite the high cost, to raise trough IgG levels to 5–7 g/l, but underlines that some categories of infectious events (non‐respiratory, upper respiratory) may need parallel surgical or pharmacological approaches to be optimally prevented or treated.
Signs of reversing trends in prevalence of asthma
Authors: von Hertzen L. , Haahtela T.
Published: January 2005

Several recent reports have provided evidence that the burden of asthma may have levelled off, after increasing for decades. Implementation of the national and global asthma prevention and management guidelines that have led to earlier detection and improved treatment of asthmatics, is considered to be involved in this apparent change for the better. In addition, environmental influences associated with the modern life may have reached the maximum in inducing symptoms and disease in genetically susceptible individuals in some areas. Available data obtained from Canada and non‐English‐speaking countries in Europe show that the peak in asthma prevalence has been reached at the level of 8–12%. This review outlines the most recent literature on time trends in asthma prevalence and considers the possible causes of the current trends. Problems and pitfalls in appraising studies on time trends are also discussed.
Use of magnetic beads to extract fungal DNA
Authors: Faggi E. , Pini G. , Campisi E.
Published: January 2005

Authors compare two methods of extracting DNA from different fungi: the classic method with phenol/chloroform (P/C) and that with magnetic beads. Both were tested on Candida albicans and Cryptococcus neoformans var. neoformans, belonging to the yeast group and Microsporum canis, M. gypseum, Trichophyton rubrum, T. interdigitale, T. ajelloi, Epidermophyton floccosum, belonging to the dermatophytes group. Extraction products underwent polymerase chain reaction (PCR) fingerprinting with the appropriate primers to point out any disagreement in the genomic profiles. After having determined that the genomic profiles obtained from the DNA extracted from the same strain with the two methods correspond perfectly, the authors concluded that the extraction method with magnetic beads from fungal cells is simpler and quicker than with P/C extraction, greatly facilitating the obtainment of fungal DNA.
Reassessment of the in vitro synergistic effect of fluconazole with the non‐steroidal anti‐inflammatory agent ibuprofen against Candida albicans
Authors: Arai R. , Sugita T. , Nishikawa A.
Published: January 2005

We reassessed the in vitro synergistic effect of fluconazole with the non‐steroidal anti‐inflammatory agent ibuprofen against the pathogenic yeast Candida albicans. No synergistic effect of fluconazole combined with ibuprofen was seen against fluconazole‐susceptible strains, but a remarkable effect was seen against fluconazole‐resistant strains (FIX index: 0.02–0.03). Furthermore, vigorous growth of the microorganism, the so‐called ‘Eagle effect’, was observed at concentrations higher than the minimal inhibitory concentrations of ibuprofen and fluconazole. Our results suggest that the combination of ibuprofen and fluconazole should prove useful for treating infection caused by fluconazole‐resistant C. albicans.
Comparison of phospholipase and proteinase activity in Candida albicans and C. dubliniensis
Authors: Fotedar R. , Al‐Hedaithy S. S. A.
Published: January 2005

Although the production of virulence enzymes by Candida albicans has been extensively explored, little attention has been given to the virulence factors of C. dubliniensis. In the present study, an attempt was made to investigate phospholipase activity (Pz value) and secretory aspartyl proteinase production of C. dubliniensis and compare it with C. albicans. None of the 87 C. dubliniensis isolates tested, produced phosholipases whereas, in contrast all the 52 (100%) C. albicans isolates tested demonstrated varying degree of phospholipase activity (Pz value: 0.37–0.74), with 35 (67.3%) of them eliciting a higher phospholipase activity (Pz values between 0.37 and 0.50). Only 32% of the C. dubliniensis isolates exhibited moderate activity (score of 1+) of secretory aspartyl proteinase whereas a vast majority (68%) of them were non‐proteolytic. On the contrary, a strong proteinase activity (score of 2+) was observed for 79% of C. albicans while the remaing 21% isolates showed moderate proteinase activity (score of 1+). As phospholipases and aspartyl proteinases of C. albicans are considered important virulence factors, the absence or lowered expression of these enzymes in C. dubliniensis may indicate the less virulent nature of this novel yeast species when compared with C. albicans.
Cutaneous sporotrichosis in Himachal Pradesh, India
Authors: Mahajan V. K. , Sharma N. L. , Sharma R. C. , Gupta M. L. , Garg G. , Kanga A. K.
Published: January 2005

During the period 1990–2002 in Himachal Pradesh, India, 103 new patients with cutaneous sporotrichosis were detected. Lymphocutaneous and fixed cutaneous varieties were the most common and seen in 49% and 43% respectively. Chronic non‐specific inflammation without granuloma formation was seen in 46% skin biopsy specimens, 29% showed acute or chronic inflammation and tuberculoid granuloma formation was seen in 25%. In 32% of cases Sporothrix schenckii growth was seen on Sabouraud glucose agar. A saturated solution of potassium iodide was used as first‐line treatment and in 93% patients healing of lesions occurred in 4–32 weeks (average 8.7 weeks) without significant side‐effects. Itraconazole, used in 12 patients, was highly effective in recommended doses. Rapid healing was seen with higher than previously used doses of fluconazole in one patient who also had unusual exacerbation of lesional inflammation with saturated solution of potassium iodide.
Pansinusitis due to Sporothrix schenckii
Authors: Kumar R. , Kaushal V. , Chopra H. , Gupta R. , Chhina D. K. , Kaushal R. K. , Mohan U.
Published: January 2005

A case of mucocutaneous sporotrichosis presenting as mycotic pansinusitis with polyposis with intracranial and intraorbital extension in a patient from Punjab, India is described. The patient had nasal discharge, sneezing and nasal obstruction for 12 years, had undergone repeated surgeries (for endoscopic clearance) but had recurrence. Computerized tomography (CT) and magnetic resonance imaging (MRI) findings revealed pansinusitis. A definitive diagnosis of sporotrichosis was established by culture of Sporothrix schenckii, verification of its dimorphic character and a positive pathogenicity test. The patient was successfully treated with potassium iodide and itraconazole.
Tinea manuum bullosa
Authors: Aste N. , Pau M. , Aste N.
Published: January 2005

We report a case of tinea manuum bullosa in a 36‐year‐old male, a crop and livestock farmer by trade. The lesion, resembling contact dermatitis, was located in the palm of the right hand. We isolated Trichophyton verrucosum. No other skin lesion was detected. Blood chemistry and immunology test results were normal. Treatment with terbinafine 250 mg day−1 led to clinical and mycological healing.
Epidemiology of dermatomycoses in children living in Northern Greece 1996–2000
Authors: Koussidou‐Eremondi Thalia , Devliotou‐Panagiotidou Despina , Mourellou‐Tsatsou Olga , Minas A.
Published: January 2005

In the 5‐years period, 1996–2000, 1045 children under 13 years old were examined for suspected dermatomycosis. In 611 cases fungi were isolated. Male children were mainly affected on the scalp and body area. Girls were more affected in the location of the arms and legs. There was a greater proportion of cases in the age range 2–12 years. The most prominent fungus wasMicrosporum canis(515 cases) followed byTrichophyton rubrum(34) andCandida albicans(20). Tinea capitis (280 cases) mainly caused byM. canis(276 cases) was the most common clinical form. Tinea corporis (109 cases) mainly caused byM. canis(88 cases),C. albicans(10 cases) andT. rubrum(seven cases) was the second most frequent clinical form.
Proven pulmonary cryptococcosis due to capsule‐deficient Cryptococcus neoformans does not differ clinically from proven pulmonary cryptococcosis due to capsule‐intact Cr. neoformans
Authors: Torres H. A. , Prieto V. G. , Raad I. I. , Kontoyiannis D. P.
Published: January 2005

We compared the clinical manifestations, laboratory and radiologic findings, and outcomes of eight patients with proven pulmonary cryptococcosis (PC) caused by capsule‐deficient Cryptococcus neoformans with those of six patients with PC caused by capsule‐intact Cr. neoformans. The presentations and outcomes did not differ significantly between the groups.
Trichophyton rubrum‐induced inflammatory tinea capitis in a 63‐year‐old man
Authors: Ziemer A. , Kohl K. , Schröder G.
Published: January 2005

Tinea capitis caused by Trichophyton rubrum is a rare event worldwide. We report on an elderly otherwise healthy man with inflammatory fungal disease of the scalp caused by this pathogen. He had no signs of concomitant mycosis of the skin and nails and no underlying immunosuppressive disease. The fungal infection primarily had been misdiagnosed in terms of a pyoderma. Failure of antibiotic treatment, a positive mycological study and molecular diagnostics eventually led to the correct diagnosis. After systemic and local administration of terbinafine the lesion improved totally.
Surgical margin status after radical retropubic prostatectomy
Authors: Khan Masood A. , Partin Alan W.
Published: January 2005

This month there are two mini‐reviews on aspects of prostate cancer. The first, from the USA, presents the implications of surgical margin status after radical prostatectomy and the potential role of adjuvant radiation therapy. The second, from the USA and Belgium, discusses the use of hormonal therapy for PSA‐only recurrence of prostate cancer after previous local therapy.

In the third mini‐review, the condition known as hypoactive sexual desire disorder is described, and that it is often ignored or erroneously treated as erectile dysfunction suggests to the authors that education of doctors and patients is required. Finally, there is a mini‐review of conventional and alternative methods for providing analgesia in renal colic.
Lymph node metastases in non‐muscle invasive bladder cancer are correlated with the number of transurethral resections and tumour upstaging at radical cystectomy
Authors: Wiesner Christoph , Pfitzenmaier Jesco , Faldum Andreas , Gillitzer Rolf , Melchior Sebastian W. , Thüroff Joachim W.
Published: January 2005

The first paper in this section, from Mainz, attempts to identify the clinical variables associated with the prevalence of lymph node metastases in non‐muscle invasive bladder cancer. The authors found that delay in cystectomy in this potentially dangerous type of tumour is to be avoided, with a higher incidence of lymph node metastases as the number of transurethral resections increases.

A paper from Austria shows that in renal carcinoma the pT1 subdivision is associated with differences in conventional histopathology and expression of biomarkers.

OBJECTIVE

To identify clinical variables associated with the prevalence of lymph node metastases (LNMs) in patients with non‐muscle invasive transitional cell carcinoma (TCC) of the bladder treated with radical cystectomy.

PATIENTS AND METHODS

Of 866 patients treated by radical cystectomy and pelvic lymphadenectomy between 1989 and 2002, 219 had non‐muscle invasive TCC of the bladder. A retrospective evaluation of these patients included univariate and multivariate analyses of sex, age, number of transurethral resections of the bladder tumour (TURBTs), interval between first TURBT and cystectomy, adjuvant therapy, maximum histopathological tumour stage and grade at TURBT, and tumour upstaging in the cystectomy specimen.

RESULTS

LNMs were diagnosed in 33 patients (15%). After multivariate analysis modelling, the number of TURBTs and tumour upstaging in the cystectomy specimen were correlated with the prevalence of LNMs at cystectomy. The number of TURBTs increased the prevalence of LNMs from 8% in patients with one TURBT to 24% in those with two to four TURBTs. Tumour upstaging in the cystectomy specimen increased the prevalence of LNMs from 4% to 36%.

CONCLUSION

Inappropriate delay and inadequate staging of high‐grade non‐muscle invasive TCC of the bladder are to be avoided. The present multivariate analysis showed that the number of TURBTs and tumour upstaging in the cystectomy specimen correlated with an increased prevalence of LNMs.
Urinary acetonitrile concentrations correlate with recent smoking behaviour
Authors: Pinggera Germar‐Michael , Lirk Philip , Bodogri Florian , Herwig Ralf , Steckel‐Berger Gabriele , Bartsch Georg , Rieder Josef
Published: January 2005

OBJECTIVES

To assess the concentration of acetonitrile (a saturated aliphatic nitrile) in the urine of habitual cigarette smokers and non‐smokers, as exposure to smoke can be measured by monitoring ambient air or byin vivotests, but acetonitrile measured in exhaled breath is reportedly a quantitative marker of recent smoking behaviour.

SUBJECTS AND METHODS

The study included 101 volunteers (57 men and 44 women, mean age 49 years). An absence of urinary tract infection on urine analysis or clinical history was mandatory. The subjects were classified into five groups, i.e. a control group of non‐smokers and four groups according to the number of cigarettes smoked daily. Urine samples were stored at 8 °C until acetonitrile was measured, within 24 h of collection, using proton‐transfer reaction mass spectrometry (PTR‐MS). Each measurement was repeated at least 10 times, and the mean used for statistical analysis.

RESULTS

The mean (sd) acetonitrile level in the urine of 46 non‐smokers was 3.74 (1.78) parts per billion volatile (ppbv). The concentration of acetonitrile increased with the number of cigarettes smoked daily, the highest concentration being in the subgroup of 13 very heavy smokers (>30 cigarettes/day) with means up to 28.04 (5.38) ppbv.

CONCLUSION

PTR‐MS is a quick, noninvasive online method for determining urinary acetonitrile levels, a marker for recent active and passive smoking behaviour, and thus for checking compliance. As smoking has been shown to affect the genesis of bladder cancer, further studies are required to determine the association of acetonitrile with bladder cancer.