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Susceptible Individuals (susceptible + individual)
Selected AbstractsChildhood cancer,mainly curable so where next?ACTA PAEDIATRICA, Issue 4 2000AW Craft More than 70% of childhood cancer is now curable with best modern therapy. The treatment is expensive but in terms of cost per life year saved, USD 1750, compares very favourably with other major health interventions. The rate of improvement in survival is slowing down. New, "designer", treatments are needed and, better still, prevention. The causes of childhood cancer are beginning to emerge. The origin for many is probably in utero and may be initiated by dietary and other environmental exposures perhaps in susceptible individuals. However, one of the great challenges for the future must be to extend the benefits of modern treatment to the 80% of the world's children who currently have little or no access to it in economically disadvantaged and emerging nations. The International Paediatric Oncology Society (SIOP) is leading the way in bringing hope for children with cancer worldwide. In India, with the support of the WHO, there is a "train the trainers" programme. In Africa, pilot studies of cost-effective treatments for Burkitt's lymphoma are producing gratifying results in Malawi and there are several examples of twinning programmes between major centres in developed and less well-developed countries. Conclusions: The future for children with cancer is bright. Most are curable and prevention may be just over the horizon. [source] Alcohol and violence and the possible role of serotoninCRIMINAL BEHAVIOUR AND MENTAL HEALTH, Issue 1 2003Abdulla A.-B. Background There is undisputed evidence linking alcohol consumption and violence and other forms of aggressive behaviour, and also linking aggression with dysfunction of the brain indolylamine serotonin (5-hydroxytryptamine or 5-HT). Alcohol consumption also causes major disturbances in the metabolism of brain serotonin. In particular, acute alcohol intake depletes brain serotonin levels in normal (non-alcohol-dependent) subjects. On the basis of the above statements, it is suggested that, at the biological level, alcohol may induce aggressive behaviour in susceptible individuals, at least in part, by inducing a strong depletion of brain serotonin levels. Aims In this article, evidence supporting these interrelationships and interactions will be summarized and discussed, the alcohol,serotonin,aggression hypothesis will be reiterated, and potential intervention strategies will be proposed. Copyright © 2003 Whurr Publishers Ltd. [source] Dexamethasone alters F-actin architecture and promotes cross-linked actin network formation in human trabecular meshwork tissueCYTOSKELETON, Issue 2 2005Abbot F. Clark Abstract Elevated intraocular pressure is an important risk factor for the development of glaucoma, a leading cause of irreversible blindness. This ocular hypertension is due to increased hydrodynamic resistance to the drainage of aqueous humor through specialized outflow tissues, including the trabecular meshwork (TM) and the endothelial lining of Schlemm's canal. We know that glucocorticoid therapy can cause increased outflow resistance and glaucoma in susceptible individuals, that the cytoskeleton helps regulate aqueous outflow resistance, and that glucocorticoid treatment alters the actin cytoskeleton of cultured TM cells. Our purpose was to characterize the actin cytoskeleton of cells in outflow pathway tissues in situ, to characterize changes in the cytoskeleton due to dexamethasone treatment in situ, and to compare these with changes observed in cell culture. Human ocular anterior segments were perfused with or without 10,7 M dexamethasone, and F-actin architecture was investigated by confocal laser scanning microscopy. We found that outflow pathway cells contained stress fibers, peripheral actin staining, and occasional actin "tangles." Dexamethasone treatment caused elevated IOP in several eyes and increased overall actin staining, with more actin tangles and the formation of cross-linked actin networks (CLANs). The actin architecture in TM tissues was remarkably similar to that seen in cultured TM cells. Although CLANs have been reported previously in cultured cells, this is the first report of CLANs in tissue. These cytoskeletal changes may be associated with increased aqueous humor outflow resistance after ocular glucocorticoid treatment. Cell Motil. Cytoskeleton 60:83,95, 2005. © 2004 Wiley-Liss, Inc. [source] The efficacy of dantrolene sodium in controlling exertional rhabdomyolysis in the Thoroughbred racehorseEQUINE VETERINARY JOURNAL, Issue 7 2003J. G. T. Edwards Summary Reasons for performing study: Dantrolene sodium (Dantrium) has been used extensively for the treatment of myopathies in man and anecdotal evidence suggests it is of clinical benefit in the control of exercise-induced rhabdomyolysis (ER) in racehorses, although data to support this are currently lacking. Objectives: To investigate the efficacy of oral dantrolene sodium in controlling ER in a randomised, double-blind, placebo-controlled crossover trial involving 77 Thoroughbred racehorses in Newmarket, UK. Methods: Horses were treated on 2 occasions 1 week apart, with treatment days coinciding with a return to exercise following 2 days box rest on each occasion. For the first treatment, each horse was randomly selected to receive either 800 mg dantrolene sodium or a colour- matched placebo administered orally 1 h before exercise. This was followed by crossover to the other treatment on the second occasion, with each horse thereby acting as its own control. Degree of ER was assessed using rising serum creatine kinase (CK) levels, by subtracting pre-exercise blood CK levels from those measured in 6 h post exercise blood samples. For each horse, the difference in change between pre- and post exercise CK values between placebo and dantrolene treatments was calculated, with positive values indicating a greater rise with placebo than with dantrolene sodium treatment. Results: The overall mean difference for all horses was +104.8 iu/l and the null hypothesis, that there was no true difference in non-normally distributed post exercise rises in CK values between placebo and dantrolene treatments, was rejected (P = 0.0013) using the nonparametric Wilcoxon signed rank test. Additionally, no horses given dantrolene sodium showed clinical signs of ER, whereas 3 horses given the placebo developed ER following exercise. The incidence of ER in the study was 4% (3/77). Conclusions: The results confirmed that oral administration of dantrolene sodium, 1 h before exercise, had a statistically significant effect on reducing the difference between pre - and post exercise plasma CK levels compared with a placebo in the same animals, and preventing clinical ER in susceptible individuals. Potential relevance: This study suggested that dantrolene sodium is of use in controlling ER in the Thoroughbred racehorse. Further investigation into pre- and post exercise myoplasmic calcium levels and the repeat of the study late in the season when horses receive a much higher energy ration and more strenuous exercise would appear to be warranted. [source] Ocular complications of neurological therapyEUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2005S. Hadjikoutis Treatments used for several neurological conditions may adversely affect the eye. Vigabatrin-related retinal toxicity leads to a visual field defect. Optic neuropathy may result from ethambutol and isoniazid, and from radiation therapy. Posterior subcapsular cataract is associated with systemic corticosteroids. Transient refractive error changes may follow treatment with acetazolamide or topiramate, and corneal deposits and keratitis with amandatine. Intraocular pressure can be elevated in susceptible individuals by anticholinergic drugs, including oxybutynin, tolterodine, benzhexol, propantheline, atropine and amitriptyline, and also by systemic corticosteroids and by topiramate. Nystagmus, diplopia and extraocular muscle palsies can occur with antiepileptic drugs, particularly phenytoin and carbamazepine. Ocular neuromyotonia can follow parasellar radiation. Congenital ocular malformations can result from in utero exposure to maternally prescribed sodium valproate, phenytoin and carbamazepine. Neurologists must be aware of potential ocular toxicity of these drugs, and appropriately monitor for potential adverse events. [source] Frontiers and controversies in the pathobiology of vitiligo: separating the wheat from the chaffEXPERIMENTAL DERMATOLOGY, Issue 7 2009Raymond E. Boissy Abstract:, The pathogenesis of vitiligo is complex and not well understood. Genes play a role in all aspects of vitiligo pathogenesis, and studies are ongoing to identify these genes and understand their biology. There is a body of interlocking, compelling evidence supporting an autoimmune basis for most or all cases of generalized vitiligo. The development of an autoimmune disease generally involves three components; the immune system, environmental triggers and other exogenous precipitating factors, and the target tissue. In vitiligo, precipitating factors could induce melanocyte damage in genetically susceptible individuals and consequent cell death, loss of tolerance, and induction of melanocyte-directed autoimmunity. Future research will more precisely define the multiple biological events that regulate development of vitiligo. [source] Effect of suramin on the human pathogen Candida albicans: implications on the fungal development and virulenceFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2007Lys Adriana Braga-Silva Abstract Candida albicans is an opportunistic pathogen that is of growing medical importance because it causes superficial, mucosal and systemic infections in susceptible individuals. Here, the effect of suramin, a polysulfonated naphthylurea derivative, on C. albicans development and virulence was evaluated. Firstly, it was demonstrated that suramin (500 ,M) arrested its growth, showing a fungicidal action dependent on cell number. Suramin treatment caused profound changes in the yeast ultrastructure as shown by transmission electron microscopy. The more important changes were the enlargement of the fungi cytoplasmic vacuoles, the appearance of yeasts with an empty cytoplasm resembling ghost cells and a reduction in cell wall thickness. Suramin also blocked the transformation of yeast cells to the germ-tube and the interaction between C. albicans and epithelial cells. In order to ascertain that the action of suramin on C. albicans growth is a general feature instead of being strain-specific, the effects of suramin on 14 oral clinical strains isolated from healthy children and HIV-positive infants were analyzed. Interestingly, the strains of C. albicans isolated from HIV-positive patients were more resistant to suramin than strains isolated from healthy patients. Altogether, the results produced here show that suramin interfered with essential fungal processes, such as growth, differentiation and interaction with host cells. [source] Bronchopneumonia and oral health in hospitalized older patients.GERODONTOLOGY, Issue 2 2002A pilot study Abstract Aims: To correlate microbial findings obtained by bronchoalveolar lavage in pneumonia patients with the clinical situation of the oral cavity. Method: Quantitative aerobic and anaerobic cultures were carried out in 150 ml samples of bronchoalveolar lavage (BAL) obtained by means of an endoscope (Video Endoscope Pentax®) inserted per as in the infected bronchus. Material: Twenty consecutive patients with a tentative clinical diagnosis of bronchopneumonia in whom BAL was carried out for diagnostic purposes. A clinical evaluation of the oral health status (oral hygiene, caries, periodontal diseases) was subsequently carried out. Results: In seven edentulous subjects wearing complete dentures the culture of anaerobic microorganisms was negative or yielding less than 100 cfu/ml BAL. Two patients yielded high counts of S. aureus and one high counts of P. aeruginosa. In the 13 subjects with natural teeth left one showed high counts of Veillonella spp. (anaerobic)+P. aeruginosa, one high counts of Veillonella spp. +S. aureus, one high counts of P. aeruginosa + S. aureus and one high counts of E. coli. These four subjects showed poor oral hygiene, periodontal pockets and a BAL microflora consistent with periodontal pathology. Conclusion: The results of this pilot study suggest that microorganisms of denture plaque or associated with periodontal diseases may give rise to aspiration pneumonia in susceptible individuals. [source] Nuclear factor-kappaB as a molecular target for migraine therapy.HEADACHE, Issue 4 2003U Reuter Ann Neurol. 2002;51:507-516. Nitric oxide (NO) generated from inducible NO synthase (iNOS) participates in immune and inflammatory responses in many tissues. The NO donor glyceryl trinitrate (GTN) provokes delayed migraine attacks when infused into migraineurs and also causes iNOS expression and delayed inflammation within rodent dura mater. Sodium nitroprusside, an NO donor as well, also increases iNOS expression. Because inflammation and iNOS are potential therapeutic targets, we examined transcriptional regulation of iNOS following GTN infusion and the consequences of its inhibition within dura mater. We show that intravenous GTN increases NO production within macrophages. L-N(6)-(1-iminoethyl)lysine, a selective iNOS inhibitor, attenuates the NO signal, emphasizing the importance of enzymatic activity to delayed NO production. iNOS expression is preceded by significant nuclear factor kappa B (NF-kappaB) activity, as reflected by a reduction in the inhibitory protein-kappa-Balpha (IkappaBalpha) and activation of NF-kappaB after GTN infusion. IkappaBalpha degradation, NF-kappaB activation, and iNOS expression were attenuated by parthenolide (3mg/kg), the active constituent of feverfew, an anti-inflammatory drug used for migraine treatment. These findings suggest that GTN promotes NF-kappaB activity and inflammation with a time course consistent with migraine attacks in susceptible individuals. We conclude, based on results with this animal model, that blockade of NF-kappaB activity provides a novel transcriptional target for the development of anti-migraine drugs. Comment: This paper suggesting the localization of NO production in dural macrophages as part of delayed inflammation may indicate proliferation and or recruitment of these cells in migraine. Could this also be a target for drug treatment? Specifically, is the genetic transcription that leads to nitric oxide generation such a target? To amend slightly the old advertising slogan, "when Michael Moskowitz talks, we all listen." DSM and SJT [source] Migraine MLT-Down: An Unusual Presentation of Migraine in Patients With Aspartame-Triggered HeadachesHEADACHE, Issue 9 2001Lawrence C. Newman MD Aspartame, an artificial sweetener added to many foods and beverages, may trigger headaches in susceptible individuals. We report two patients with aspartame-triggered attacks in whom the use of an aspartame-containing acute medication (Maxalt-MLT) worsened an ongoing attack of migraine. [source] Primary and multisensory cortical activity is correlated with audiovisual perceptsHUMAN BRAIN MAPPING, Issue 4 2010Margo McKenna Benoit Abstract Incongruent auditory and visual stimuli can elicit audiovisual illusions such as the McGurk effect where visual /ka/ and auditory /pa/ fuse into another percept such as/ta/. In the present study, human brain activity was measured with adaptation functional magnetic resonance imaging to investigate which brain areas support such audiovisual illusions. Subjects viewed trains of four movies beginning with three congruent /pa/ stimuli to induce adaptation. The fourth stimulus could be (i) another congruent /pa/, (ii) a congruent /ka/, (iii) an incongruent stimulus that evokes the McGurk effect in susceptible individuals (lips /ka/ voice /pa/), or (iv) the converse combination that does not cause the McGurk effect (lips /pa/ voice/ ka/). This paradigm was predicted to show increased release from adaptation (i.e. stronger brain activation) when the fourth movie and the related percept was increasingly different from the three previous movies. A stimulus change in either the auditory or the visual stimulus from /pa/ to /ka/ (iii, iv) produced within-modality and cross-modal responses in primary auditory and visual areas. A greater release from adaptation was observed for incongruent non-McGurk (iv) compared to incongruent McGurk (iii) trials. A network including the primary auditory and visual cortices, nonprimary auditory cortex, and several multisensory areas (superior temporal sulcus, intraparietal sulcus, insula, and pre-central cortex) showed a correlation between perceiving the McGurk effect and the fMRI signal, suggesting that these areas support the audiovisual illusion. Hum Brain Mapp, 2010. © 2009 Wiley-Liss, Inc. [source] An unusual distribution of the kdr gene among populations of Anopheles gambiae on the island of Bioko, Equatorial GuineaINSECT MOLECULAR BIOLOGY, Issue 6 2005L. J. Reimer Abstract In West Africa, Anopheles gambiae exists in discrete subpopulations known as the M and S molecular forms. Although these forms occur in sympatry, pyrethroid knock-down resistance (kdr) is strongly associated with the S molecular form. On the island of Bioko, Equatorial Guinea we found high frequencies of the kdr mutation in M form individuals (55.8%) and a complete absence of kdr in the S form. We also report the absence of the kdr allele in M and S specimens from the harbour town of Tiko in Cameroon, representing the nearest continental population to Bioko. The kdr allele had previously been reported as absent in populations of An. gambiae on Bioko. Contrary to earlier reports, sequencing of intron-1 of this sodium channel gene revealed no fixed differences between M form resistant and susceptible individuals. The mutation may have recently arisen independently in the M form on Bioko due to recent and intensive pyrethroid application. [source] The infectivity of transmissible spongiform encephalopathy agent at low doses: the importance of phospholipidJOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2006P. Gale Abstract The issue of whether the mechanism of infection is independent or co-operative for low doses of transmissible spongiform encephalopathy (TSE) agent is critical for risk assessment. The susceptibility (and hence ID50) of individuals with the same prion protein (PrP) genotype may vary considerably with a small proportion being very susceptible. Assuming independent action, the incubation period (IP) would continue to increase until the dose is below the ID50 of the most susceptible individuals in the experiment, at which point it would become constant. This may explain the observed increase in IP with decreasing dose below the apparent ID50 in experiments with untreated TSE agent. In contrast, IPs for autoclaved or NaOH-treated TSE agent increase greatly at doses Probiotics and their fermented food products are beneficial for healthJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2006S. Parvez Abstract Probiotics are usually defined as microbial food supplements with beneficial effects on the consumers. Most probiotics fall into the group of organisms' known as lactic acid-producing bacteria and are normally consumed in the form of yogurt, fermented milks or other fermented foods. Some of the beneficial effect of lactic acid bacteria consumption include: (i) improving intestinal tract health; (ii) enhancing the immune system, synthesizing and enhancing the bioavailability of nutrients; (iii) reducing symptoms of lactose intolerance, decreasing the prevalence of allergy in susceptible individuals; and (iv) reducing risk of certain cancers. The mechanisms by which probiotics exert their effects are largely unknown, but may involve modifying gut pH, antagonizing pathogens through production of antimicrobial compounds, competing for pathogen binding and receptor sites as well as for available nutrients and growth factors, stimulating immunomodulatory cells, and producing lactase. Selection criteria, efficacy, food and supplement sources and safety issues around probiotics are reviewed. Recent scientific investigation has supported the important role of probiotics as a part of a healthy diet for human as well as for animals and may be an avenue to provide a safe, cost effective, and ,natural' approach that adds a barrier against microbial infection. This paper presents a review of probiotics in health maintenance and disease prevention. [source] The presence of local and circulating autoreactive B cells in patients with advanced periodontitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 4 2002Tord Berglundh Abstract Aim: The aim of the present investigation was to study the local (gingival) and systemic occurrence of autoreactive B cells (CD5+CD19 positive) in subjects with a high or low susceptibility to periodontitis. Material and Methods: 2 groups of subjects (Group A and B) susceptible to periodontitis were included. Group A consisted of 22 adult patients (7 females and 15 males, aged 24,66 years) with advanced and generalized chronic periodontitis and group B comprised 7 children (4 girls and 3 boys aged 9,13 years) with localized aggressive periodontitis. 26 periodontally healthy subjects, Group C (aged 23,80 years, mean 49.6±16.3), were also recruited. Assessment of clinical and radiographical characteristics of periodontal disease was performed. Gingival biopsies and peripheral blood samples were obtained and prepared for immunohistochemical analysis. Blood samples only were obtained from the periodontally healthy subjects (group C). Results: The proportion of autoreactive B cells (CD5+CD19 positive) of peripheral blood lymphocytes was about 6 times higher in group A and 4 times higher in group B than in the samples from the control subjects (group C). About 40,50% of the B cells in the peripheral blood of the periodontitis susceptible individuals expressed markers for autoreactive features while less than 15% of the circulating B cells in the subjects of group C exhibited such markers. The periodontitis lesion in the adult periodontitis patients contained a substantial number of B cells out of which about 30% demonstrated autoreactive features. Conclusion: It is suggested that both circulating and local B cells in periodontitis susceptible individuals have a higher propensity to autoreactive properties than B cells of patients with a low susceptibility to periodontitis. Zusammenfassung Zielsetzungen: Untersuchung des lokalen (in der Gingiva) und systemischen Vorkommens autoreaktiver B-Zellen (CD5 und CD19 positiv) bei Individuen mit hoher und niedriger Anfälligkeit für Parodontitis. Material und Methoden: 2 Gruppen von Personen, die anfällig für Parodontitis waren, nahmen an der Studie teil: Gruppe A: 22 erwachsenen Patienten (im Alter von 24,66 Jahren; 7 weiblich) mit fortgeschrittener generalisierter chronischer Parodontitis; Gruppe B: 7 Kinder (9,13 Jahre; 4 Mädchen) mit lokalisierter aggressiver Parodontitis. Zusätzlich wurden 26 parodontal gesunde Personen (23,80 Jahre) untersucht. Klinische und röntgenologische parodontale Parameter wurden erhoben. In den Gruppen A und B, wurden Gingivabiopsien und periphere Blutproben, in Gruppe C nur Blutproben entnommen. Ergebnisse: Der Anteil autoreaktiver B-Zellen an den Lymphozyten im peripheren Blut war etwa 6 mal höher in gruppe A und 4 mal höher in Gruppe B als in Proben der Kontrollgruppe (Gruppe C). Etwa 40,50% der B-Zellen im peripheren Blut der für Parodontitis anfälligen Patienten exprimierten Marker für autoreaktive Eigenschaften während weniger als 15% der zirkulierenden B-Zellen der Individuen aus Gruppe C solche Marker aufwiesen. Die parodontalen Läsionen der erwachsenen Parodontitispatienten enthielten eine hohe Zahl von B-Zellen, von denen etwa 30% autoreaktive Eigenschaften aufwiesen. Schlussfolgerungen: Sowhol lokale als auch zirkulierende B-Zellen von für Parodontitis anfälligen Patienten zeigen mit größerer Häufigkeit autoreaktive Eigenschaften als die B-Zellen von Patienten mit geringer Parodontitisanfälligkeit. Résumé But: Le but de cette recherche était d'étudier la présence locale (gingivale) et systémique de cellules B auto réactives (CD5+CD19 positives) chez des sujets présentant une forte ou une faible susceptibilitéà la parodontite. Matériaux et méthodes: 2 groupes de sujet (A et B) susceptible à la parodontite furent inclus. Le groupe A était constitué de 22 patients adultes (7 femmes et 15 hommes âgés de 24 a 66 ans) présentant une parodontite chronique avancée et généralisée et le groupe B était constitué de 7 enfants (4 filles et 3 garçons ages de 9 à 13 ans) présentant une pardontite agressive localisée. 26 sujets sains d'un point de vue parodontal (groupe C, âgés de 23 à 80 ans, age moyen 49.6±16.3) furent également recrutés. L'observation des caractéristiques cliniques et radiographiques de la maladie parodontale fut réalisée. Des biopsies gingivales et des échantillons sanguins furent prélevées et préparées pour des analyses immunohistochemiques. Seuls des prélèvements sanguins furent pris sur le groupe des patients sains. Résultats: La proportion de cellules B auto réactives (CD5+CD19 positives) des lymphocytes du sang périphérique était 6× plus élevée dans le groupe A et 4× plus élevée dans le groupe B que chez les sujets contrôles du groupe C. Environ 40 a 50% des cellules B du sang périphérique des individus susceptibles à la parodontite exprimaient des marqueurs pour des caractéristiques auto réactives alors que moins de 15% des cellules B circulantes des sujets du groupe C présentaient de tels marqueurs. La lésion parodontale de patients atteints de parodontite de l'adulte contenait un nombre substantiel de cellule B parmi lesquels environ 30% présentaient des caractéristiques auto réactives. Conclusions: Cela suggère que les cellules B locales et circulantes des individus susceptibles à la maladie parodontale aient une puls grande propension aux propriétés auto réactives que les cellules B des patients ayant une susceptibilité faible à la parodontite. [source] Detection of Chlamydia pneumoniae by polymerase chain reaction,enzyme immunoassay in intestinal mucosal biopsies from patients with inflammatory bowel disease and controlsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2002Wangxue Chen Abstract Background and Aim : It has been suggested that Chlamydia is an organism that may have the potential to cause inflammatory bowel disease (IBD) in susceptible individuals. Chlamydia pneumoniae has emerged as an important human pathogen in the last decade. The objective of the present study was to investigate the frequency of the presence of C. pneumoniae DNA in intestinal biopsies from patients with IBD and from non-IBD controls. Methods : The DNA was extracted from 222 colonoscopic biopsies, which were obtained from 11 patients with Crohn's disease (CD), 18 patients with ulcerative colitis (UC) and from 37 non-IBD control patients. The presence of the C. pneumoniae omp1 gene and C. trachomatis 16S rRNA gene was determined using a rapid and sensitive polymerase chain reaction-enzyme immunoassay (PCR-EIA). Results : The C. pneumoniae -specific DNA was detected in 32 (14.4%) of 222 endoscopic biopsies. Among them, C. pneumoniae DNA were found in nine of 42 (21.4%) biopsies from patients with CD, nine of 59 (15.3%) biopsies from patients with UC, and 14 out of 122 (11.4%) biopsies from non-IBD control patients, respectively. Moreover, the percentage of patients with at least one biopsy positive for C. pneumoniae was higher, although not statistically significant, in CD (36.4%) and UC patients (38.9%) compared to non-IBD controls (16.2%). In contrast, C. trachomatis DNA was detected in only two of 222 (0.9%) biopsy samples. Conclusion : The C. pneumoniae DNA was detected in the intestine of both patients with IBD and in non-IBD control patients, probably reflecting the high prevalence of this organism in the environment. The moderate yield of positive biopsies in our IBD patients and the fact that the detection rate of C. pneumoniae DNA was similar in endoscopic biopsies from IBD patients and non-IBD controls does not support a direct role for this organism in the pathogenesis of IBD. © 2002 Blackwell Publishing Asia Pty Ltd [source] Is susceptibility to tuberculosis acquired or inherited?JOURNAL OF INTERNAL MEDICINE, Issue 2 2007E. Schurr Abstract. Tuberculosis is an ongoing major public health problem on a global scale. One of the striking features of the disease is that only an estimated 10% of immunocompetent persons infected by the causative pathogen Mycobacterium tuberculosis will develop clinical signs of disease. This well-established epidemiological observation has prompted an intense search for the factors that trigger advancement of infection to disease in the small proportion of susceptible individuals. Central to this search is the questions if tuberculosis patients are inherently susceptible to the disease or if disease development is promoted by specific environmental factors. It is known that genetic and non-genetic factors of both the bacterium and the host have impact on the host response to M. tuberculosis. Yet, little is known about the interaction of these different factors and the resulting impact on disease development. Recent work suggests that in addition to common host susceptibility genes a second group of susceptibility loci exists the action of which strongly depends on the individual's clinical and exposure history. The latter genes may have a very strong effect on promoting advancement from infection to disease only in specific epidemiological settings. These findings suggest that a more detailed knowledge of gene,environment interactions in tuberculosis is necessary to understand why a small proportion of individuals are susceptible to the disease whilst the majority of humans are naturally resistant to tuberculosis. [source] Environmental triggers of type 1 diabetesJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 3 2001JJ Couper Abstract: High risk HLA class II alleles account for 40% of the genetic susceptibility to type 1 diabetes in Caucasians, but the majority of the genetically predisposed do not develop the disease. This supports some environmental modification of the autoimmune destruction of , cells that precedes type 1 diabetes. Identical twin studies and geographical variation in incidence also argue for a critical role of environmental factors. Attention has been directed to the possible harmful effect of cow's milk protein (or protective effect of breast-feeding) and enteric infections in early life. Natural history studies that follow children at increased risk of type 1 diabetes provide the best opportunity to study environmental triggers. The Australian Baby Diab Study has followed approximately 500 babies from birth who have a first-degree relative with type 1 diabetes. No prospective association between duration of breast-feeding or introduction of cow's milk and the development of islet autoimmunity was found. The same Australian cohort demonstrated a relationship between rotavirus infection and the first appearance or increase in islet antibodies. Enteroviral infection is seen more frequently in prediabetic children and prior to the onset of islet autoimmunity in Finnish cohorts. Environmental factors may interact. Breast milk protects against enteric infections; enteric infections in turn could increase immunity to dietary antigens by increasing intestinal permeability. It is also possible that an alteration in gut mucosal immune function in genetically susceptible individuals underlies any effect of dietary or viral proteins on the development of islet autoimmunity in early life. [source] Monitoring periodontal disease status in smokers and nonsmokers using a gingival crevicular fluid matrix metalloproteinase-8-specific chair-side testJOURNAL OF PERIODONTAL RESEARCH, Issue 6 2006P. Mäntylä Background and Objective:, With current periodontal diagnostic tools it is difficult to identify susceptible individuals or sites at risk. The aim of this study was to evaluate the efficacy of the matrix metalloproteinase (MMP)-8-specific chair-side dip-stick test in longitudinally monitoring the periodontal status of smoking (S) and nonsmoking (NS) patients with chronic periodontitis, using their gingival crevicular fluid (GCF) MMP-8 concentrations. Material and Methods:, Clinical parameters, MMP-8 test results and concentrations were monitored in 16 patients after initial treatment and in 15 patients after scaling and root planing (SRP), every other month, over a 12-mo time period. Progressing and stable sites, and sites with exceptionally high MMP-8 concentrations, were analysed in smokers and nonsmokers. Results:, SRP reduced the mean GCF MMP-8 levels, test scores, probing depth (PD), attachment loss (AL) and bleeding on probing (BOP). In sites of periodontal disease progression, the distribution of MMP-8 concentrations was broader than in stable sites, indicating a tendency for elevated concentrations in patients with periodontal disease. The mean MMP-8 concentrations in smokers were lower than in nonsmokers, but in smokers' and nonsmokers' sites with progressive disease, MMP-8 concentrations were similar. Sites with exceptionally elevated MMP-8 concentrations were clustered in smokers who also showed a poor response to SRP. In these sites, the MMP-8 concentration did not decrease with SRP and these sites were easily identified by the MMP-8 test. Conclusion:, Persistently elevated GCF MMP-8 concentrations may indicate sites at risk, as well as patients with poor response to conventional periodontal treatment (e.g. SRP). MMP-8 testing may be useful as an adjunct to traditional periodontal diagnostic methods during the maintenance phase. [source] Against the grain: An overview of celiac diseaseJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 5 2008FNP-C Clinical Instructor, Suzanne Martin RN Abstract Purpose: To review the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of celiac disease (CD). Data sources: Review of literature using Pub Med and Access Medicine. The following search terms were used: celiac disease, malabsorption syndromes, diarrhea, and gluten-free diet (GFD). There was no limitation placed on publication year. Only articles written in English were included. Conclusions: CD is a chronic systemic autoimmune disorder triggered in genetically susceptible individuals by the ingestion of gluten proteins (wheat, barley, and rye). CD often presents atypically, and diagnosis delays are common. Currently, the only effective treatment for CD is strict adherence to a GFD. This is a difficult diet to comprehend and follow. Adherence to a GFD requires ongoing education and support from a multidisciplinary healthcare team, support groups, family, and friends. Implications for practice: Once considered a rare disease of childhood, CD is now recognized as a common disorder that can occur at any age. Clinicians need to be cognizant of risk factors, clinical manifestations, conditions, and complications associated with CD in order to make a timely diagnosis, ameliorate symptoms, and minimize disease complications. [source] A nutrition and health perspective on almondsJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 14 2006Chung-Yen Chen Almonds provide a nutrient-dense source of vitamin E, manganese, magnesium, copper, phosphorus, fibre, riboflavin, monounsaturated fatty acids and protein. Although almost 50% of almond weight is fat, incremental intakes of 7 g day,1 of this tree nut reduce low-density lipoprotein (LDL) cholesterol concentration by 1%, especially within the context of diets recommended by the National Cholesterol Education Program. Habitual almond consumption does not lead to weight gain, and their inclusion in low-calorie diets appears to promote more weight loss than a comparable carbohydrate-based low-calorie diet. Also, almonds have a low glycemic index and do not adversely impact insulin sensitivity. Almonds are an excellent source of bioavailable ,-tocopherol, and increasing their intake enhances the resistance of LDL against oxidation. In addition, the polyphenolic constituents of almonds have been characterised recently and found to possess antioxidant actions. While benefits of almonds for cardiovascular health and obesity-related diseases appear promising, the potential allergenic reaction among susceptible individuals can present a risk. Further research is required to achieve a better understanding of the role that the bioavailability and bioaccessibility of almond constituents and the synergy between them play in their associated health outcomes. Copyright © 2006 Society of Chemical Industry [source] Review article: safe amounts of gluten for patients with wheat allergy or coeliac diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2006C. HISCHENHUBER Summary For both wheat allergy and coeliac disease the dietary avoidance of wheat and other gluten-containing cereals is the only effective treatment. Estimation of the maximum tolerated amount of gluten for susceptible individuals would support effective management of their disease. Literature was reviewed to evaluate whether an upper limit for gluten content in food, which would be safe for sufferers from both diseases, could be identified. When setting gluten limits for coeliac disease sufferers, the overall potential daily intake should be considered, while for wheat allergy limits should be based on single servings. For coeliac disease sufferers this limit should lie between 10 and 100 mg daily intake. For wheat allergy, lowest eliciting doses for children lie in the lower milligram range, while for adults they are most significantly higher. Gliadins (part of the gluten proteins) not only trigger coeliac disease, but are also major allergens in wheat allergy. Therefore, measurement of gliadins with validated enzyme-linked immunosorbent assay methods provides an appropriate marker for assessing gluten and/or wheat protein contents in food. Available data suggest that a maximum gluten content for ,gluten-free' foods could be set, which protects both wheat allergy sufferers and coeliac patients. [source] Allergy assessment of foods or ingredients derived from biotechnology, gene-modified organisms, or novel foodsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 6 2004Lars K. Poulsen Abstract The introduction of novel proteins into foods carries a risk of eliciting allergic reactions in individuals sensitive to the introduced protein and a risk of sensitizing susceptible individuals. No single predictive test exists to perform a hazard assessment in relation to allergenic properties of newly expressed proteins in gene-modified organisms (GMOs). Instead, performance of a weighted risk analysis based on the decision tree approach has been suggested. The individual steps of this analysis comprise sequence homology to known allergens, specific or targeted serum screens for immunoglobulin E (IgE) cross-reactions to known allergens, digestability studies of the proteins in simulated gastric and/or intestinal fluids, and animal studies. These steps are discussed and five examples of risk evaluation of GMOs or novel foods are presented. These include ice-structuring protein derived from fish, microbial transglutaminase, GMO-soybeans, amylase and the Nangai nut. [source] The place of suxamethonium in pediatric anesthesiaPEDIATRIC ANESTHESIA, Issue 6 2009MARCIN RAWICZ MD Summary Suxamethonium is a drug that promotes very strong views both for and against its use in the context of pediatric anesthesia. As such, the continuing debate is an excellent topic for a ,Pro,Con' debate. Despite ongoing efforts by drug companies, the popular view still remains that there is no single neuromuscular blocking drug that can match suxamethonium in terms of speed of onset of neuromuscular block and return of neuromuscular control. However, with this drug the balance of benefit vs risk and side effects are pivotal. Suxamethonium has significant adverse effects, some of which can be life threatening. This is particularly relevant for pediatric anesthesia because the spectrum of childhood diseases may expose susceptible individuals to an increased likelihood of adverse events compared with adults. Additionally, the concerns related to airway control in the infant may encourage the occasional pediatric anesthetist to use the drug in preference to slower onset/offset drugs. In the current environment of drug research, surveillance and licensing, it is debatable whether this drug would achieve the central place it still has in pediatric anesthesia. The arguments for and against its use are set out below by our two international experts, Marcin Rawicz from Poland and Barbara Brandom from USA. This will allow the reader an objective evaluation with which to make an informed choice about the use of suxamethonium in their practice. [source] Resistance to cyfluthrin and tetrachlorvinphos in the lesser mealworm, Alphitobius diaperinus, collected from the eastern United StatesPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 7 2006Ronda L Hamm Abstract The lesser mealworm, Alphitobius diaperinus (Panzer), is an important pest in poultry facilities. The toxicity of cyfluthrin and tetrachlorvinphos to five strains of the lesser mealworm was compared with the toxicity to a susceptible laboratory strain. Bioassays were carried out with both larvae and adults. For the susceptible strain, cyfluthrin and tetrachlorvinphos had similar toxicity to adults, but cyfluthrin was 5 times more toxic to larvae when compared with tetrachlorvinphos. High levels of resistance to tetrachlorvinphos in two beetle strains were detected in both larvae and adults, although these strains were heterogeneous and still contained susceptible individuals. Resistance to cyfluthrin ranged from 1.7- to 9.5-fold for adults and from 0.5- to 29-fold for larvae at the LC95. Overall, the patterns of resistance did not mirror the insecticide use patterns reported at these facilities. The implications of these results to management of the lesser mealworms are discussed. Copyright © 2006 Society of Chemical Industry [source] Does Cerumen Have a Risk for Transmission of Hepatitis B?,THE LARYNGOSCOPE, Issue 3 2004M. Tayyar Kalcioglu MD Abstract Objectives/Hypothesis Chronic hepatitis B virus infection is a significant worldwide health problem. It affects 350 to 400 million people. The patients with chronic hepatitis B virus infection have a significant risk for the development of cirrhosis or hepatocellular carcinoma. Full awareness of the mechanisms of transmission can allows susceptible individuals to refrain from this infection. Cerumen has never been studied as a route for hepatitis B transmission. The aim of the study was evaluate the importance of cerumen in transmission of hepatitis B virus infection. Study Design This study was performed on forty patients with confirmed hepatitis B virus infection. Methods Forty cerumen specimens collected from the patients with hepatitis B virus DNA in their sera were prospectively analyzed for the presence of hepatitis B virus DNA by real-time polymerase chain reaction. Results Eleven of 40 cerumen specimens (27.5%) were positive for hepatitis B virus DNA, with counts ranging from 4.2 × 102 to 4.7 × 106 copies per sample. There was positive correlation between hepatitis B virus DNA concentrations of serum and cerumen. Half of hepatitis B e antigen (HBeAg),positive patients had detectable hepatitis B virus DNA levels (5.7 × 102 to 4.7 × 106 copies) in cerumen specimens, whereas 12.5% of cerumen specimens from anti-HBe,positive patients had hepatitis B virus DNA levels (4.2 × 102 to 7.0 × 103 copies). Conclusion Cerumen can be a potential source of transmission. Therefore, this route should be investigated in further studies for horizontal, nosocomial, and occupational transmission of hepatitis B. [source] Plasmin immunization preferentially induces potentially prothrombotic IgG anticardiolipin antibodies in MRL/MpJ miceARTHRITIS & RHEUMATISM, Issue 10 2009Kaleo Ede Objective To test the hypothesis, utilizing 2 experimental mouse models, that plasmin is an important autoantigen that drives the production of certain IgG anticardiolipin (aCL) antibodies in patients with the antiphospholipid syndrome. Methods BALB/cJ and MRL/MpJ mice were immunized with Freund's complete adjuvant in the presence or absence of human plasmin. The mouse sera were analyzed for production of IgG antiplasmin, IgG aCL, and IgG anti,,2 -glycoprotein I (anti-,2GPI) antibodies. IgG monoclonal antibodies (mAb) were generated from the plasmin-immunized MRL/MpJ mice with high titers of aCL, and these 10 mAb were studied for their binding properties and functional activity in vitro. Results Plasmin-immunized BALB/cJ mice produced high titers of IgG antiplasmin only, while plasmin-immunized MRL/MpJ mice produced high titers of IgG antiplasmin, IgG aCL, and IgG anti-,2GPI. Both strains of mice immunized with the adjuvant alone did not develop IgG antiplasmin or IgG aCL. All 10 of the IgG mAb bound to human plasmin and cardiolipin, while 4 of 10 bound to ,2GPI, 3 of 10 bound to thrombin, and 4 of 10 bound to the activated coagulation factor X (FXa). Functionally, 4 of the 10 IgG mAb inhibited plasmin activity, 1 of 10 hindered inactivation of thrombin by antithrombin III, and 2 of 10 inhibited inactivation of FXa by antithrombin III. Conclusion Plasmin immunization leads to production of IgG antiplasmin, aCL, and anti-,2GPI in MRL/MpJ mice, but leads to production of only IgG antiplasmin in BALB/cJ mice. IgG mAb generated from plasmin-immunized MRL/MpJ mice bind to various antigens and exhibit procoagulant activity in vitro. These results suggest that plasmin may drive potentially prothrombotic aCL in genetically susceptible individuals. [source] Crystallization and preliminary X-ray analysis of mycophenolic acid-resistant and mycophenolic acid-sensitive forms of IMP dehydrogenase from the human fungal pathogen CryptococcusACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 9 2010Carl A. Morrow Fungal human pathogens such as Cryptococcus neoformans are becoming an increasingly prevalent cause of human morbidity and mortality owing to the increasing numbers of susceptible individuals. The few antimycotics available to combat these pathogens usually target fungal-specific cell-wall or membrane-related components; however, the number of these targets is limited. In the search for new targets and lead compounds, C. neoformans has been found to be susceptible to mycophenolic acid through its target inosine monophosphate dehydrogenase (IMPDH); in contrast, a rare subtype of the related C. gattii is naturally resistant. Here, the expression, purification, crystallization and preliminary crystallographic analysis of IMPDH complexed with IMP and NAD+ is reported for both of these Cryptococcus species. The crystals of IMPDH from both sources had the symmetry of the tetragonal space group I422 and diffracted to a resolution of 2.5,Å for C. neoformans and 2.6,Å for C. gattii. [source] The role of transforming growth factor-,1 and oxidative stress in podoconiosis pathogenesisBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2010S. Addisu Summary Background, Podoconiosis (endemic nonfilarial elephantiasis) occurs in susceptible individuals who go barefoot in regions of irritant volcanic soil. Silicate particles absorbed via the skin are thought to induce an inflammatory process and a consequent endolymphangitis of the lower leg lymphatics. Objectives, To establish which oxidative stress biomarkers play a part in the inflammatory process, and to test whether transforming growth factor (TGF)-,1 also has a pathogenetic role. Patients and methods, We enrolled 50 patients with early clinical stage disease, 43 patients with advanced stage disease and 35 local healthy controls. Oxidative stress biomarkers included serum total peroxides (TP), total antioxidant capacity (TAC), total nitrate plus nitrite (TN), malondialdehyde (MDA) and total superoxide dismutase (SOD) activity. The oxidative stress index (OSI) was also determined. Serum total TGF-,1 was assayed using sandwich enzyme-linked immunosorbent assay. Results, Compared with healthy controls, patients with early stage disease showed significantly higher mean levels of TP (P < 0·001), MDA (P < 0·05) and OSI (P < 0·01); and significantly lower mean concentrations of SOD (P < 0·001) and TGF-,1 (P < 0·001). Mean levels of TGF-,1 were even lower among patients with advanced stage disease (P < 0·001). Mean TAC levels were significantly lower among patients with advanced disease than either other group (P < 0·001). Conclusions, This is the first study, to our knowledge, to attempt to elucidate the molecular pathogenetic events in podoconiosis. We conclude that TGF-,1 may have a pathogenetic role, with oxidative stress playing a minor role in the early stages of disease. [source] The immune recognition of gluten in coeliac diseaseCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005R. Ciccocioppo Summary Coeliac disease, the most common intestinal disorder of western populations, is an autoimmune enteropathy caused by an abnormal immune response to dietary gluten peptides that occurs in genetically susceptible individuals carrying the HLA-DQ2 or -DQ8 haplotype. Despite the recent progresses in understanding the molecular mechanisms of mucosal lesions, it remains unknown how increased amounts of gluten peptides can enter the intestinal mucosa to initiate the inflammatory cascade. Current knowledge indicates that different gluten peptides are involved in the disease process in a different manner, some fragments being ,toxic' and others ,immunogenic'. Those defined as ,toxic' are able to induce mucosal damage either when added in culture to duodenal endoscopic biopsy or when administered in vivo, while those defined as ,immunogenic' are able to specifically stimulate HLA-DQ2- or DQ8-restricted T cell clones isolated from jejunal mucosa or peripheral blood of coeliac patients. These peptides are able to trigger two immunological pathways: one is thought to be a rapid effect on the epithelium that involves the innate immune response and the other represents the adaptive immune response involving CD4+ T cells in the lamina propria that recognize gluten epitopes processed and presented by antigen presenting cells. These findings are the subject of the present review. [source]
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