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Severe Form (severe + form)
Selected AbstractsAcute Cellular Rejection Predominated by Monocytes Is a Severe Form of Rejection in Human Renal Recipients With or Without Campath-1H (Alemtuzumab) Induction TherapyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2005Ping L. Zhang Campath-1H has been used successfully for induction and has resulted in a low rate of acute cellular rejection (ACR) in renal transplantation in combination with various postoperative immunosuppression regimens. This study was undertaken to investigate the extent of monocyte involvement in ACR, with or without Campath-1H induction. We found that monocytes represented the majority of inflammatory cells in grades Ib or higher ACR, but not with Ia type of ACR, regardless of the status of Campath-1H induction. Cases of ACR, following Campath-1H induction, appear to demonstrate a ,pure form' of monocytic ACR, whereas monocytes were mixed with many other types of inflammatory cells in the cases of ACR in the absence of Campath-1H induction. In addition with Campath-1H induction, the cases of monocyte-predominant ACR were found to uniformly exhibit a good response to corticosteroid treatment. We conclude that monocyte-predominate ACR may represent a severe form of rejection, with or without Campath-1H treatment. [source] Alopecia areata in Turkey: demographic and clinical featuresJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 8 2008A Kavak Abstract Background, Alopecia areata is a complex genetic disease with still many unknown aspects, and many studies have been tried to find some clues about it. Objective, We aimed to investigate the demographic and clinical characteristics of alopecia areata in Turkish patients. Methods, Demographic data, localization, attack number in addition to some parameters such as disease duration, severity, age of onset, family history and ophiasis pattern were evaluated in 539 alopecia areata patients. Results, The male to female ratio was 1.6 : 1. Occipital and beard-moustache areas were mostly affected. Positive family history was noticed in 24.1% of the patients. The age of onset was earlier in women than in men (P = 0.04). Severe forms showed more persistent (, 1 year) disease duration (P = 0.00). Ophiasis was more common in severe, long duration (, 1 year) and early onset (, 18 years) disease (P = 0.00 for all parameters). Childhood alopecia areata (, 18 years) was also associated with long duration of the disease (P = 0.016) and positive family history (P = 0.008) when compared with adult onset (> 18 years) alopecia areata. [source] Generalized social phobia and avoidant personality disorder: meaningful distinction or useless duplication?,DEPRESSION AND ANXIETY, Issue 1 2008Dianne L. Chambless Ph.D. Abstract Participants with generalized social phobia (GSP) with (n=36) and without (n=19) avoidant personality disorder (AVPD) were compared via contrasts of group means and classification analysis on purported core features of AVPD. GSP-AVPD participants proved to be more severely impaired or distressed on some group contrasts. Cluster analysis identified two groups in the sample, with group membership significantly correlated to AVPD diagnosis. However, almost all significant findings were nullified when severity of social phobia was statistically controlled. Thus, at least where participants with social phobia are concerned, it seems most parsimonious to consider AVPD a severe form of GSP rather than a separate diagnostic category. Depression and Anxiety 0:1,12 2006. Published 2006 Wiley-Liss, Inc. [source] The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticityDEVELOPMENTAL NEUROBIOLOGY, Issue 5 2010Eero Castrén Abstract Recent evidence suggests that neuronal plasticity plays an important role in the recovery from depression. Antidepressant drugs and electroconvulsive shock treatment increase the expression of several molecules, which are associated with neuronal plasticity, in particular the neurotrophin BDNF and its receptor TrkB. Furthermore, these treatments increase neurogenesis and synaptic numbers in several brain areas. Conversely, depression, at least in its severe form, is associated with reduced volumes of the hippocampus and prefrontal cortex and in at least some cases these neurodegenerative signs can be attenuated by successful treatment. Such observations suggest a central role for neuronal plasticity in depression and the antidepressant effect, and also implicate BDNF signaling as a mediator of this plasticity. The antidepressant fluoxetine can reactivate developmental-like neuronal plasticity in the adult visual cortex, which, under appropriate environmental guidance, leads to the rewiring of a developmentally dysfunctional neural network. These observations suggest that the simple form of the neurotrophic hypothesis of depression, namely, that deficient levels of neurotrophic support underlies mood disorders and increases in these neurotrophic factors to normal levels brings about mood recovery, may not sufficiently explain the complex process of recovery from depression. This review discusses recent data on the role of BDNF and its receptors in depression and the antidepressant response and suggests a model whereby the effects of antidepressant treatments could be explained by a reactivation of activity-dependent and BDNF-mediated cortical plasticity, which in turn leads to the adjustment of neuronal networks to better adapt to environmental challenges. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 2010 [source] Mating compatibility, life-history traits, and RAPD-PCR variation in Bemisia tabaci associated with the cassava mosaic disease pandemic in East AfricaENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 1 2001M.N. Maruthi Abstract The pandemic of a severe form of cassava mosaic virus disease (CMVD) in East Africa is associated with abnormally high numbers of its whitefly vector, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). To determine whether a novel B. tabaci biotype was associated with the CMVD pandemic, reproductive compatibility, fecundity, nymphal development, and random amplified polymorphic DNA (RAPD) variability were examined in, and between, B. tabaci colonies collected from within the CMVD pandemic and non-pandemic zone in Uganda. In a series of reciprocal crosses carried out over two generations among the six CMVD pandemic and four non-pandemic zone cassava B. tabaci colonies, there was no evidence of mating incompatibility. All the crosses produced both female and male progeny in the F1 and F2 generations, which in a haplo-diploid species such as B. tabaci indicates successful mating. There also were no significant differences between the sex ratios for the pooled data of experimental crosses, between individuals from two different colonies and control crosses between individuals from the same colony. Only one instance of mating incompatibility occurred in a control cross between cassava B. tabaci from Uganda and cotton B. tabaci from India. Measures of fecundity of the pandemic and non-pandemic zone B. tabaci on four cassava varieties showed no significant differences in their fecundity, nymphal development or numbers surviving to adult eclosion. Cluster analysis of 26 RAPD bands using six 10-mer primers was concordant with the mating results, grouping the pandemic and non-pandemic zone colonies into a single large group, also including a B. tabaci colony collected from cassava in Tanzania. These results suggest that it is unlikely that the severe CMVD pandemic in East Africa is associated with a novel and reproductively isolated B. tabaci biotype. [source] MAPK3 deficiency drives autoimmunity via DC armingEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2010Ivo Bendix Abstract DC are professional APC that instruct T cells during the inflammatory course of EAE. We have previously shown that MAPK3 (Erk1) is important for the induction of T-cell anergy. Our goal was to determine the influence of MAPK3 on the capacity of DC to arm T-cell responses in autoimmunity. We report that DC from Mapk3,/, mice have a significantly higher membrane expression of CD86 and MHC-II and , when loaded with the myelin oligodendrocyte glycoprotein , show a superior capacity to prime naïve T cells towards an inflammatory phenotype than Mapk3+/+ DC. Nonetheless and as previously described, Mapk3,/, mice were only slightly but not significantly more susceptible to myelin oligodendrocyte glycoprotein-induced EAE than WT littermate mice. However, Mapk3+/+ mice engrafted with Mapk3,/, BM (KO,WT) developed a severe form of EAE, in direct contrast to WT,KO mice, which were even less sick than control WT,WT mice. An infiltration of DC and accumulation of Th17 cells was also observed in the CNS of KO,WT mice. Therefore, triggering of MAPK3 in the periphery might be a therapeutic option for the treatment of neuroinflammation since absence of this kinase in the immune system leads to severe EAE. [source] Neuroserpin Portland (Ser52Arg) is trapped as an inactive intermediate that rapidly forms polymersFEBS JOURNAL, Issue 16 2004Implications for the epilepsy seen in the dementia FENIB The dementia familial encephalopathy with neuroserpin inclusion bodies (FENIB) is caused by point mutations in the neuroserpin gene. We have shown a correlation between the predicted effect of the mutation and the number of intracerebral inclusions, and an inverse relationship with the age of onset of disease. Our previous work has shown that the intraneuronal inclusions in FENIB result from the sequential interaction between the reactive centre loop of one neuroserpin molecule with ,-sheet A of the next. We show here that neuroserpin Portland (Ser52Arg), which causes a severe form of FENIB, also forms loop-sheet polymers but at a faster rate, in keeping with the more severe clinical phenotype. The Portland mutant has a normal unfolding transition in urea and a normal melting temperature but is inactive as a proteinase inhibitor. This results in part from the reactive loop being in a less accessible conformation to bind to the target enzyme, tissue plasminogen activator. These results, with those of the CD analysis, are in keeping with the reactive centre loop of neuroserpin Portland being partially inserted into ,-sheet A to adopt a conformation similar to an intermediate on the polymerization pathway. Our data provide an explanation for the number of inclusions and the severity of dementia in FENIB associated with neuroserpin Portland. Moreover the inactivity of the mutant may result in uncontrolled activity of tissue plasminogen activator, and so explain the epileptic seizures seen in individuals with more severe forms of the disease. [source] Complete physical map and gene content of the human NF1 tumor suppressor region in human and mouseGENES, CHROMOSOMES AND CANCER, Issue 2 2003Dieter E. Jenne Duplicon-mediated microdeletions around the NF1 gene are frequently associated with a severe form of neurofibromatosis type I in a subgroup of patients who show an earlier onset of cutaneous neurofibromas, dysmorphic facial features, and lower IQ values. To clarify the discrepancies between published maps of the NF1 tumor-suppressor gene region as well as the length of gaps in these assemblies and to validate the recently described tandem duplication of the human NF1 locus, we assembled a contiguous high-density map of BAC and PAC clones from different genomic libraries. Although two WI-12393,derived low-copy fragments are known to occur at the proximal and distal boundaries of the 1.5-Mb segment that is usually deleted in NF1 microdeletion patients, we identified an additional WI-12393,related segment between the MGC13061 and the NF1 gene, which appears to trigger interstitial deletions of smaller size as observed in two patients. Moreover, we completed the genomic organization and cDNA structure of all functional genes, CYTOR4, FLJ12735, FLJ22729, CENTA2, MGC13061, NF1, OMG, EVI2B, EVI2A, KIAA1821, MGC11316, HCA66, KIAA0160, and WI-12393, from this region. A comparison of the human map to the orthologous region on mouse chromosome 11 revealed significant differences in the number and arrangement of genes, indicating that many chromosomal breaks with partial duplications, inversions, and deletions occurred predominantly in the primate lineage. © 2003 Wiley-Liss, Inc. [source] Knowledge of disease and adherence in adult patients with haemophiliaHAEMOPHILIA, Issue 4 2010K. LINDVALL Summary., Patients with moderate and severe haemophilia are evaluated on a regular basis at their haemophilia centres but patients with mild haemophilia are seen less often because of fewer problems related to their disease. The needs of patients with milder forms of haemophilia, however, are often underestimated, both by the patient and staff at healthcare facilities. This study evaluated the knowledge of disease and adherence to treatment among patients with severe, moderate and mild haemophilia. This was a prospective multicentre study performed in Haemophilia Centres in Scandinavia. A total of 413 (67%) of 612 patients aged >25 years with mild, moderate and severe haemophilia completed a self-administered questionnaire. The mean age of the respondents was 49.7 years (range 25,87 years). Of the 413 respondents, 150 had a mild, 86 had a moderate and 177 had a severe form of haemophilia. A total of 22 (5%) patients did not know the severity of their disease, and 230 (56%) patients knew the effect of factor concentrate in the blood. Of the 413 respondents, 53 (13%) of the cohort never treated a haemorrhage. Patients with mild haemophilia, P , 0.001, were the least likely to treat a haemorrhage. The relative number of patients who were afraid of virus transmission by factor concentrate was about similar in the three groups, 27% of those with severe haemophilia, 26% with moderate and 24% with mild haemophilia. This study shows that the amount of knowledge among haemophilia patients about their disease and treatment is somewhat limited, and demonstrates the importance of continually providing information about haemophilia and treatment, especially to patients with a mild form of the disease. [source] Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression,HEPATOLOGY, Issue 6 2009Kimberley D. Bruce Nonalcoholic fatty liver disease (NAFLD) describes an increasingly prevalent spectrum of liver disorders associated with obesity and metabolic syndrome. It is uncertain why steatosis occurs in some individuals, whereas nonalcoholic steatohepatitis (NASH) occurs in others. We have generated a novel mouse model to test our hypothesis: that maternal fat intake contributes to the development of NAFLD in adult offspring. Female mice were fed either a high-fat (HF) or control chow (C) diet before and during gestation and lactation. Resulting offspring were fed either a C or a HF diet after weaning, to generate four offspring groups; HF/HF, HF/C, C/HF, C/C. At 15 weeks of age, liver histology was normal in both the C/C and HF/C offspring. Kleiner scoring showed that although the C/HF offspring developed nonalcoholic fatty liver, the HF/HF offspring developed NASH. At 30 weeks, histological analysis and Kleiner scoring showed that both the HF/C and C/HF groups had NAFLD, whereas the HF/HF had a more severe form of NASH. Therefore, exposure to a HF diet in utero and during lactation contributes toward NAFLD progression. We investigated the mechanisms by which this developmental priming is mediated. At 15 weeks of age, hepatic mitochondrial electron transport chain (ETC) enzyme complex activity (I, II/III, and IV) was reduced in both groups of offspring from HF-fed mothers (HF/C and HF/HF). In addition, measurement of hepatic gene expression indicated that lipogenesis, oxidative stress, and inflammatory pathways were up-regulated in the 15-week-old HF/C and HF/HF offspring. Conclusion: Maternal fat intake contributes toward the NAFLD progression in adult offspring, which is mediated through impaired hepatic mitochondrial metabolism and up-regulated hepatic lipogenesis. (HEPATOLOGY 2009.) [source] A missense mutation in FIC1 is associated with greenland familial cholestasisHEPATOLOGY, Issue 6 2000Leo W. J. Klomp Greenland familial cholestasis is a severe form of intrahepatic cholestasis described among indigenous Inuit families in Greenland. Patients present with jaundice, pruritus, bleeding episodes, and steatorrhea, and die in childhood due to end-stage liver disease. We investigated the possibility that Greenland familial cholestasis is caused by a mutation in FIC1, the gene defective in patients with progressive familial intrahepatic cholestasis type 1 and many cases of benign recurrent intrahepatic cholestasis. Using single-strand conformation polymorphism analysis and sequencing of the FIC1 exons, a missense mutation, 1660 G,A (D554N), was detected and was shown to segregate with the disease in Inuit patients from Greenland and Canada. Examination of liver specimens from 3 Inuit patients homozygous for this mutation revealed bland canalicular cholestasis and, on transmission electron microscopy, coarsely granular Byler bile, as previously described in patients with progressive familial intrahepatic cholestasis type 1. These data establish Greenland familial cholestasis as a form of progressive familial intrahepatic cholestasis type 1 and further underscore the importance of unimpeded FIC1 activity for normal bile formation. [source] Sex difference in the liver of hepatocyte-specific Pten-deficient mice: A model of nonalcoholic steatohepatitisHEPATOLOGY RESEARCH, Issue 6 2009Yumiko Anezaki Aim:, Nonalcoholic fatty liver disease (NAFLD) is considered to be a public health problem worldwide. NAFLD is more prevalent in men than in women. Tamoxifen, a potent estrogen receptor antagonist, causes nonalcoholic steatohepatitis (NASH), a severe form of NAFLD. Thus, there may be a sex difference that is dependent on estrogens in NAFLD and NASH. Hepatocyte-specific Pten-deficient mice exhibit hepatic lesions analogous to NASH and are considered to be a clinical model of NASH. We aimed to shed light on any sex differences in the hepatic lesions of Pten-deficient mice and the underlying mechanisms. Methods:, At 40 weeks, livers from male and female Pten-deficient mice were processed for measuring lipid content, genes expression analysis, and histological examination. Level of serum reactive oxygen species (ROS) was also determined. Seventy-six-week-old mice were used in tumor burden experiments. Results:, Hepatic steatosis, inflammation, and even carcinogenesis in Pten-deficient mice were attenuated in females compared to males. Attenuated fatty liver in females was ascribed to inactivation of sterol regulatory element binding protein-1c. Hepatic inflammation in females was suppressed via decreased ROS with increased antioxidant gene expression and decreased proinflammatory cytokine production. Anti-cancer effect in female mice was, at least in part, due to the significantly lower ratio of oleic to stearic acid in the liver. Conclusions:, Hepatic lesions in Pten-deficient mice were attenuated in females compared to males, as were human NAFLD and NASH. Some of the underlying mechanisms in sex difference appeared to be due to the change of gene expression, dependent on estrogens. [source] Plectin deficiency leads to both muscular dystrophy and pyloric atresia in epidermolysis bullosa simplex,HUMAN MUTATION, Issue 10 2010Ken Natsuga Abstract Plectin is a cytoskeletal linker protein which has a long central rod and N- and C-terminal globular domains. Mutations in the gene encoding plectin (PLEC) cause two distinct autosomal recessive subtypes of epidermolysis bullosa: EB simplex (EBS) with muscular dystrophy (EBS-MD), and EBS with pyloric atresia (EBS-PA). Previous studies have demonstrated that loss of full-length plectin with residual expression of the rodless isoform leads to EBS-MD, whereas complete loss or marked attenuation of expression of full-length and rodless plectin underlies the more severe EBS-PA phenotype. However, muscular dystrophy has never been identified in EBS-PA, not even in the severe form of the disease. Here, we report the first case of EBS associated with both pyloric atresia and muscular dystrophy. Both of the premature termination codon-causing mutations of the proband are located within exon 32, the last exon of PLEC. Immunofluorescence and immunoblot analysis of skin samples and cultured fibroblasts from the proband revealed truncated plectin protein expression in low amounts. This study demonstrates that plectin deficiency can indeed lead to both muscular dystrophy and pyloric atresia in an individual EBS patient. © 2010 Wiley-Liss, Inc. [source] Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis: report of 20 novel mutations,HUMAN MUTATION, Issue 1 2010Alessandra Pangrazio Abstract The "Osteopetroses" are genetic diseases whose clinical picture is caused by a defect in bone resorption by osteoclasts. Three main forms can be distinguished on the basis of severity, age of onset and means of inheritance: the dominant benign, the intermediate and the recessive severe form. While several genes have been involved in the pathogenesis of the different types of osteopetroses, the CLCN7 gene has drawn the attention of many researchers, as mutations within this gene are associated with very different phenotypes. We report here the characterization of 25 unpublished patients which has resulted in the identification of 20 novel mutations, including 11 missense mutations, 6 causing premature termination, 1 small deletion and 2 putative splice site defects. Careful analysis of clinical and molecular data led us to several conclusions. First, intermediate osteopetrosis is not homogeneous, since it can comprise both severe dominant forms with an early onset and recessive ones without central nervous system involvement. Second, the appropriateness of haematopoietic stem cell transplantation in CLCN7-dependent ARO patients has to be carefully evaluated and exhaustive CNS examination is strongly suggested, as transplantation can almost completely cure the disease in situations where no primary neurological symptoms are present. Finally, the analysis of this largest cohort of CLCN7-dependent ARO patients together with some ADO II families allowed us to draw preliminary genotype-phenotype correlations suggesting that haploinsufficiency is not the mechanism causing ADO II. The availability of biochemical assays to characterize ClC-7 function will help to confirm this hypothesis. © 2009 Wiley-Liss, Inc. [source] Human natural killer cell receptors and co-receptorsIMMUNOLOGICAL REVIEWS, Issue 1 2001Roberto Biassoni Summary: In the absence of sufficient signaling by their HLA class I-specific inhibitory receptors, human natural killer (NK) cells become activated and display potent cytotoxicity against cells that are either HLA class I negative or deficient. This indicates that the NK receptors responsible for the induction of cytotoxicity recognize ligands on target cells different from HLA class I molecules. On this basis, the process of NK-cell triggering can be considered as a mainly non-MHC-restricted mechanism. The recent identification of a group of NK-specific triggering surface molecules has allowed a first series of pioneering studies on the functional/molecular characteristics of such receptors. The first three members of a receptor family that has been termed natural cytotoxicity receptors (NCR) are represented by NKp46, NKp44 and NKp30. These receptors are strictly confined to NK cells, and their engagement induces a strong activation of NK-mediated cytolysis. A direct correlation exists between the surface density of NCR and the ability of NK cells to kill various target cells. Importantly, mAb-mediated blocking of these receptors has been shown to suppress cytotoxicity against most NK-susceptible target cells. However, the process of NK-cell triggering during target cell lysis may also depend on the concerted action of NCR and other triggering receptors, such as NKG2D, or surface molecules, including 2B4 and NKp80, that appear to function as co-receptors rather than as true receptors. Notably, a dysfunction of 2B4 has been associated with a severe form of immunodeficiency termed X-linked lymphoproliferative disease. Future studies will clarify whether also the altered expression and/or function of other NK-triggering molecules may represent a possible cause of immunological disorders. This work was supported by grants awarded by Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.), Istituto Superiore di Sanità (I.S.S.), Ministero della Sanità, and Ministero dell'Università e della Ricerca Scientifica e Tecnologica (M.U.R.S.T.) and Consiglio Nazionale delle Ricerche, Progetto Finalizzato Biotecnologie. The financial support of Telethon-Italy (grant no. E.0892) is gratefully acknowledged. [source] The challenge of ST-segment elevation myocardial infarctionINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 12 2007M. Cohen Summary Background/introduction:, Acute coronary syndromes (ACS) represent a spectrum of ischaemic myocardial events that share a similar pathophysiology. ST-segment elevation myocardial infarction (STEMI), the most severe form of ACS short of sudden cardiac death, is a significant public health problem with an estimated 500,000 STEMI events every year in the United States. Treatment/therapy:, The mortality and morbidity associated with STEMI is significant. Early reperfusion therapy is the most important aspect of the treatment of STEMI. There are two main methods of reperfusion therapy: percutaneous coronary intervention (PCI) and fibrinolytic therapy, with PCI being the preferred method. In addition to standard reperfusion therapy, antithrombotics (unfractionated heparin and low molecular weight heparins) and antiplatelet agents (aspirin, clopidogrel and glycoprotein IIb/IIIa inhibitors) are critical adjuncts, effective in the treatment of acute STEMI. Conclusions:, The survival of patients with STEMI depends on rapid diagnosis and optimal early treatment. Guidelines for the management of patients with STEMI recommend PCI within 90 min of presentation and that fibrinolytics are administered within 30 min. However, only a fraction of patients undergo reperfusion within the recommended time. Improvements in protocols for identifying STEMI cases are therefore required to allow reperfusion therapy to be initiated sooner. Secondary prevention is another important aspect of STEMI management, and patients should be encouraged to adopt strategies that reduce the risk of subsequent ischaemic events. [source] Unilateral sacroiliitis associated with systemic isotretinoin treatmentINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2010Mauro Barbareschi MD Background, Acne fulminans is the most severe form of inflammatory acne characterized by the acute onset of inflammatory nodules and plaques, most commonly on the chest and the back. The lesions undergo rapid suppuration, leaving ragged hemorrhagic ulcers. Typically, it affects adolescent males with a history of mild to moderate acne. The affected patients often have constitutional symptoms such as fever, malaise, arthralgias, and myalgias. Leukocytosis is commonly associated. Sacroiliitis is reported in 21% of acne fulminans patients in association with arthritis and in a few cases it is reported during isotretinoin treatment, suggesting the drug triggering. Conclusion, We report a case of a young male patient in whom the induction of acne fulminans by systemic isotretinoin was associated with unilateral sacroiliitis. [source] A panel of multiple markers associated with chronic systemic inflammation and the risk of atherogenesis is detectable in asthma and chronic obstructive pulmonary diseaseJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 6 2007Tsu-Lan Wu Abstract Asthma and chronic obstructive pulmonary disease (COPD) are both lung diseases involving chronic inflammation of the airway. The injury is reversible in asthma whereas it is mostly irreversible in COPD. Both patients of asthma and COPD are known at risk for cardiovascular disease (CVD) and type 2 diabetes (T2DM), nephropathy, and cancer. We measured multiple risk markers for atherogenesis in 55 patients with asthma and 62 patients with COPD. We wanted to know whether risk markers for atherogenesis corresponding to sequence of events of chronic inflammation were also detectable in the airway inflammatory diseases. Elevation of almost all markers involving inflammation of the endothelial cells in the coronary artery were detectable in asthma and COPD involving the inflammation of the epithelial cell lining of the airway. Both the level and % elevation of all markers were found mostly higher in COPD, the more severe form of the lung disease. We believe that these markers are useful for predicting risk of developing clinical complications such as CVD. J. Clin. Lab. Anal. 21:367,371, 2007. © 2007 Wiley-Liss, Inc. [source] Analysis of clinical features of acute pancreatitis in Shandong Province, ChinaJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2007Yan Jing Gao Abstract Aim:, To investigate and obtain a more comprehensive view of the etiology and clinical features of acute pancreatitis in China. Method:, The study comprised 1471 patients in 10 cites of China who were admitted to hospitals for acute pancreatitis from January 1992 to December 2002. Data for each patient were collected on a standardized form. Results:, Of the 1471 patients (854 men, 617 women; mean age 43.3 years; range 13,82 years), 1280 had mild pancreatitis and 191 had the severe form. Cholelithiasis (20.2%), alcohol (17.3%) and diet-induced (12.4%) were the most frequent etiological factors, followed by biliary tract infections (5.6%), hyperlipidemia (2.3%) and other factors (5.1%). However, in about 36.1% of cases, the etiology of acute pancreatitis still remained unexplained. In coastal regions, cholelithiasis was the most frequent factor but alcohol ranked first in interior regions. In males, a small predominance of alcohol over cholelithiasis was seen (27.4%vs 14.3%) and there was a clear predominance of cholelithiasis over alcohol (28.4%vs 3.2%) in females. The differences in the frequency of cholelithiasis and alcohol between coastal regions and interior regions and males and females were statistically significant (P < 0.01). According to their frequency, complications of acute pancreatitis were pancreatic pseudocyst, pancreatic ascities and bacterial peritonitis, pulmonary infections, multiple organ failure, diabetes mellitus type 2 and shock. Conclusion:, Cholelithiasis, alcohol and diet-induced factors were the main etiological factors seen in China, whereas cholelithiasis alone predominated in females and alcohol ranked first in males. In about 36.1% of cases, the etiology of acute pancreatitis remained unknown. More attention should be paid to studying the etiologies of acute pancreatitis that remain unknown. [source] Relationship between smoking status and periodontal conditions: findings from national databases in JapanJOURNAL OF PERIODONTAL RESEARCH, Issue 6 2006M. Ojima Background and Objective:, The association between cigarette smoking and periodontitis was examined employing two nationally representative samples of adults in Japan. Material and Methods:, Data were derived from the Survey of Dental Diseases (SDD) and the National Nutrition Survey (NNS) in 1999. In the SDD, periodontal conditions were evaluated by calibrated dentists utilizing the Community Periodontal Index (CPI), whereas in the NNS, participants were interviewed on the basis of smoking status by enumerators. Among 6805 records electronically linked via a household identification code, 4828 records of individuals aged 20 yr or older were analyzed. Results:, The prevalence of periodontal disease varied significantly by smoking status (p < 0.0001): 39.3%, 49.5% and 47.3% (CPI , 3), and 7.9%, 11.7% and 12.4% (a more severe form of periodontitis, CPI = 4), for nonsmokers, former smokers and current smokers, respectively. In adults aged ,,40 yr (n = 3493), logistic regression models revealed greater probabilities (approximately 1.4 times higher) of periodontitis [CPI , 3, odds ratio = 1.38 (1.12,1.71), p = 0.0024] and a more severe form of periodontitis [odds ratio = 1.40 (1.04,1.89), p = 0.0288] in current smokers compared with nonsmokers, following adjustment for possible confounding factors. Conclusion:, Based on the findings of this study and other numerous reports, cigarette smoking leads to deterioration of periodontal conditions in Japanese adults. [source] Effect of Alcohol Consumption on CpG Methylation in the Differentially Methylated Regions of H19 and IG-DMR in Male Gametes,Implications for Fetal Alcohol Spectrum DisordersALCOHOLISM, Issue 9 2009Lillian A. Ouko Background:, Exposure to alcohol in utero is the main attributable cause of fetal alcohol spectrum disorders (FASD) which in its most severe form is characterized by irreversible behavioral and cognitive disability. Paternal preconception drinking is not considered to be a significant risk factor, even though animal studies have demonstrated that chronic paternal alcohol consumption has a detrimental effect on the physical and mental development of offspring even in the absence of in utero alcohol exposure. It has been documented that alcohol can reduce the levels and activity of DNA methyltransferases resulting in DNA hypomethylation and that reduced methyltransferase activity can cause activation of normally silenced genes. The aim of this study was to establish a link between alcohol use in men and hypomethylation of paternally imprinted loci in sperm DNA in genomic regions critical for embryonic development, thus providing a mechanism for paternal effects in the aetiology of FASD. Methods:, Sperm DNA from male volunteers was bisulfite treated and the methylation patterns of 2 differentially methylated regions (DMRs), H19 and IG-DMR, analyzed following sequencing of individual clones. The methylation patterns were correlated with the alcohol consumption levels of the volunteer males. Results:, There was a pattern of increased demethylation with alcohol consumption at the 2 imprinted loci with a significant difference observed at the IG-DMR between the nondrinking and heavy alcohol consuming groups. Greater inter-individual variation in average methylation was observed at the H19 DMR and individual clones were more extensively demethylated than those of the IG-DMR. CpG site #4 in the IG-DMR was preferentially demethylated among all individuals and along with the H19 DMR CpG site #7 located within the CTCF binding site 6 showed significant demethylation in the alcohol consuming groups compared with the control group. Conclusion:, This study demonstrates a correlation between chronic alcohol use and demethylation of normally hypermethylated imprinted regions in sperm DNA. We hypothesize that, should these epigenetic changes in imprinted genes be transmitted through fertilization, they would alter the critical gene expression dosages required for normal prenatal development resulting in offspring with features of FASD. [source] Inherited myopathy of great DanesJOURNAL OF SMALL ANIMAL PRACTICE, Issue 5 2006A. Lujan Feliu-Pascual A hereditary, non-inflammatory myopathy occurring in young great Danes with distinctive histological features in muscle biopsy specimens is reviewed. Onset of clinical signs is usually before one year of age and both sexes are affected. Clinical signs are characterised by exercise intolerance, muscle wasting, and an exercise-induced tremor. Although most affected dogs have a severe form of the disease, occasional dogs may have a less pronounced form and survive into adulthood with an acceptable quality of life. Litters containing affected puppies are born to clinically unaffected parents, and an autosomal recessive pattern of inheritance is likely. All recorded cases have had fawn or brindle coat coloration. Elevated serum creatinine kinase concentrations and spontaneous electrical activity in skeletal muscles are frequently found. While originally reported (Targett and others 1994) as a central core myopathy in this breed, the histochemical characteristics of the distinct cytoarchitectural structures differ from those of the well-characterised central core myopathy in human beings. In fact, these structures differ from any known myopathy in human beings and likely represents a unique non-inflammatory myopathy affecting dogs. Until this myopathy is characterised further, the name inherited myopathy in great Danes is suggested. [source] Lack of association of iron metabolism and Dupuytren's diseaseJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2008J Hnanicek Abstract Background,Iron accumulation as seen in genetic haemochromatosis is a major cause of hepatic fibrogenesis. A link between chronic liver disease and Dupuytren's disease (DD) is well established, especially in alcoholics. Aim The aim of the present study was to test the hypothesis that iron accumulation might cause fibrosis of the palmar aponeurosis leading to DD. Patients and methods We examined iron metabolism, mutations of the HFE gene, serum cholesterol, alcohol consumption, presence of chronic liver disease, diabetes and history of severe manual work in a group of 90 patients who had undergone surgery for a severe form of DD. The tissue removed during surgery was histologically examined to confirm the diagnosis of DD. For a control group, we used 33 healthy subjects with similar profiles. Results The DD group consisted of 82 men and 8 women. Chronic liver disease was found in 27% of DD patients, compared with 6.1% of control subjects (P = 0.013). A history of hand traumatization was present in 33% of DD patients vs. 15% of control subjects (P = 0.048). Excessive alcohol consumption was present in 35.5% of DD patients compared with 15.1% of controls (P = 0.029). None of the other tested parameters, including the prevalence of HFE gene mutations, showed a significant difference between the two groups. Conclusions Iron accumulation does not play a major role in the pathogenesis of DD. However, sex, age, manual labour and alcohol consumption are risk factors for progression of DD. We observed a high incidence of chronic liver disease in patients with DD. [source] Dejerine-Sottas Neuropathy with Multiple Nerve Roots Enlargement and Hypomyelination Associated with a Missense Mutation of the Transmembrane Domain of MPZ/P0JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2003A Simonati In a patient affected with a slowly progressive, severe form of Dejerine-Sottas syndrome, symmetric enlargement of cranial nerves and focal hypertrophy of cervical and caudal roots were detected following MRI. Neuropathological features of the sural nerve disclosed a dramatic loss of myelinated fibres, with skewed-to-the-left, unimodal distribution of the few residual fibres, consistent with the diagnosis of congenital hypomyelination neuropathy. Genetic analysis revealed this condition to be associated with a heterozygous G to A transition at codon 167 in the exon 4 of the MPZ/P0 gene causing a Gly138Arg substitution in the transmembrane domain of the mature MPZ/P0 protein. Focal enlargement of the nerve trunks in demyelinating, hereditary motor and sensory neuropathies (HMSN) was previously reported in both asymptomatic and symptomatic cases with root compression, but peculiar to this case is the diffuse involvement of both cranial and spinal nerves. We believe that the relevance of nerve trunk hypertrophy in HMSN is probably underevaluated: therefore MRI investigation of the head and spine should be included in the diagnostic study of selected HMSN patients. Molecular analysis of peripheral myelin genes will help to rule out misdiagnosed cases. [source] Validation of a composite score for clinical severity of hemophiliaJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2008S. SCHULMAN Summary.,Introduction:,Evaluation of modulators of the phenotypic expression of hemophilia may benefit from a scoring system that reflects several aspects of the clinical severity instead of only one dimension. Methods:,We describe here how we constructed a composite Hemophilia Severity Score (HSS) and performed validation. The items in the HSS are annual incidence of joint bleeds, World Federation of Hemophilia Orthopedic joint score, and annual factor consumption. The latter two were adjusted for age at start of prophylaxis and body weight. Data for 100 adolescent or adult patients with hemophilia A or B in the mild, moderate or severe form without inhibitors were collected for the 1990,1999 period. We evaluated the reliability (multidimension property, test,retest) and validity (content, convergent, discriminant and known groups) of the score. Results:,The HSS ranged from 0 to 0.94 and was higher in severe hemophilia A than severe hemophilia B (median 0.50 and 0.24; P = 0.031). The validation indicated that the HSS is reliable and reflective of the clinical severity of hemophilia. The presence of factor V G1691A or prothrombin G20210A polymorphisms was found in 13 patients. The clinical severity, measured as the HSS or each of the three components, appeared to be modified by prothrombin G20210A but not by FV G1691A. Conclusion:,The HSS is a well-defined tool that provides a comprehensive representation of the clinical severity of hemophilia in adults. It would be useful in larger studies on the assessment of modulators of the phenotypic expression of hemophilia. [source] Fulminant liver failure from acute autochthonous hepatitis E in France: description of seven patients with acute hepatitis E and encephalopathyJOURNAL OF VIRAL HEPATITIS, Issue 5 2007J. M. Péron Summary., Fulminant hepatitis E has not been well characterized in industrialized countries. The aim of this study was to prospectively describe patients with acute hepatitis E presenting as fulminant hepatic failure, i.e. with encephalopathy and prothrombin index <50%. Between February 1997 and April 2005, seven patients with encephalopathy were diagnosed with acute hepatitis E using viral RNA detection. These patients were compared with 33 patients diagnosed with a mild form (absence of encephalopathy) of acute hepatitis E during the same time period. Patients were 65 ± 11 years old. Five were active drinkers and six had chronic liver disease. All hepatitis E virus sequences evaluated (5/7) were of genotype 3. All patients but two died (71%). Four patients had no travel history. When compared with patients with a mild form of acute hepatitis E, active alcohol abuse and chronic liver disease were more frequent in patients with the severe form. Duration of hospitalization was longer. Aspartate transferase and bilirubin levels were significantly higher. Prothrombin index and accelerin levels were lower and death was more frequent. Acute nontravel-associated hepatitis E can appear as fulminant hepatitis with encephalopathy and coagulation disorders. Prognosis is severe and this may be due to the age at which it occurs and frequent underlying chronic liver disease. [source] Post-transplant recurrent hepatitis C: immunohistochemical detection of hepatitis C virus core antigen and possible pathogenic implicationsLIVER INTERNATIONAL, Issue 6 2008Mário G. Pessôa Abstract Introduction: The mechanisms by which severe cholestatic hepatitis develops after liver transplantation are not fully understood. Reports on immunohistochemical distribution of hepatitis C virus (HCV) antigens are still scarce, but recently, HCV immunostaining was suggested for early diagnosis of cholestatic forms of recurrent hepatitis C in liver grafts. After purification, Rb246 pab anticore (aa1-68) yielded specific, granular cytoplasmic staining in hepatocytes. Signal amplification through the Envision-Alkaline Phosphatase System avoided endogenous biotin and peroxidase. Aims/Methods: Rb246 was applied to liver samples of explants of 12 transplant recipients, six with the most severe form of post-transplantation recurrence, severe cholestatic hepatitis (group 1) and six with mild recurrence (group 2). We also assessed immuno-reactivity at two time-points post-transplantation (median 4 and 22 months) in both groups. HCV-core Ag was semiquantified from 0 to 3+ in each time point. Serum HCV-RNA was also measured on the different time points by branched DNA. Results: In the early post-transplant time point, one patient had a mild staining (1+), two patients had a moderate staining (2+) and the other three had no staining in group 1, compared with five patients with no staining (0) and one patient with mild staining (1+) in group 2. Late post-transplant liver samples were available in nine patients, and two out of four samples in group 1 showed a mild staining, compared with no staining patients in five patients in group 2. Strikingly, on the explant samples, HCV immunostaining was strongly positive in group 1, and mildly positive in group 2. Two out of five samples showed 3+ staining, and three samples showed 2+ staining in group 1; two out of five samples showed no staining, two samples showed 1+ staining and one sample showed 2+ staining in group 2. Serum HCV-RNA was significantly higher in group 1, on both time-points post-transplantation. HCV-core Ag was not directly associated with serum HCV-RNA on the different time points. Conclusion: These preliminary results suggest that strong HCV immunostaining in the explant is predictive of more severe disease recurrence. [source] Characteristics of dengue virus-infected peripheral blood mononuclear cell death that correlates with the severity of illnessMICROBIOLOGY AND IMMUNOLOGY, Issue 8 2009Yanin Jaiyen ABSTRACT The pathogenic mechanism of the severe form of dengue is complicated. Recent reports indicate that apoptotic death of various tissues or organs may be associated with vascular leakage, and ultimately leads to the death of DENV-infected patients. In the present study, we provide additional evidence supporting the detrimental role of apoptosis in DENV infection. A comparison of the rate of apoptosis in PBMCs isolated from patients suffering DF, a mild form of the disease, and the rate in patients with DHF, a life-threatening disease, revealed that PBMCs from DHF patients underwent apoptosis at a significantly higher rate than those suffering from DF alone. This suggests that the severity of natural DENV infection correlates with PBMC apoptosis. In addition, this cell death was induced not only by DENV itself, but also by the apoptotic activities of pro-inflammatory cytokines, such as TNF-,, and IL-1,, that were upregulated in DHF patients. The death of these mononuclear cells that function in an innate immune system may explain the higher viral load in DHF patients than in DF patients. Interestingly, a gene expression profile pattern elucidated that apoptosis occurring during natural DENV infection involved mainly the extrinsic apoptosis pathway, which is mediated via both caspase-dependent and caspase-independent mechanisms. In conclusion, our data highlight the adverse effect of apoptosis induced by DENV and by pro-inflammatory cytokines during natural DENV infection. [source] The use of glucan as immunostimulant in the treatment of a severe case of chromoblastomycosisMYCOSES, Issue 4 2008Conceição de Maria Pedrozo E Silva Azevedo Summary We report the case of an alternative treatment for a patient with a severe form of chromoblastomycosis that responded poorly to the traditional antifungal therapy. We hereby show, in this study, the improvement of lesions after treatment with itraconazole associated with an intramuscular administration of glucan. We observed that the regression of lesions was associated with an improvement of the cellular immune response. This favourable response that we observed suggests that the therapeutic regimen we used might be an option for the treatment of patients with a severe form of chromoblastomycosis. [source] Aspergillus fumigatus peritonitis in ambulatory peritoneal dialysis: A case report and notes on the therapeutic approach (Case Report)NEPHROLOGY, Issue 3 2005LUCIANA BONFANTE SUMMARY: Aspergillus peritonitis is a rare disease in continuous peritoneal dialysis. It is a severe form of peritonitis, which is frequently lethal. We report a case of Aspergillus fumigatus peritonitis in a female patient on automated peritoneal dialysis (APD), who was successfully treated with intravenous amphotericin B and the removal of the peritoneal catheter. As delayed treatment has an increased mortality rate, it is mandatory to remove the catheter and to start intravenous treatment with amphotericin B empirically. [source] | |||||||||||||||||||||||||||||||||||||||||||