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Severe Disease (severe + disease)

Distribution by Scientific Domains

Medical Sciences	88%
Life Sciences	11%

Distribution within Medical Sciences

Dermatology	14%
Allergy & Clinical Immunology	7%
Respiratory Medicine	6%
Immunology	3%
Obstetrics & Gynecology	2%
28 Other Subdomains	63%

Selected Abstracts

Stress-Induced Wall Motion Abnormalities with Low-Dose Dobutamine Infusion Indicate the Presence of Severe Disease and Vulnerable Myocardium

ECHOCARDIOGRAPHY, Issue 7 2007
Stephen G. Sawada M.D.
Background: Patients with left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) may develop stress-induced wall motion abnormalities (SWMA) with low-dose (10 ,g/kg/min) dobutamine infusion. The clinical significance of low-dose SWMA is unknown. Objective: We investigated the clinical, hemodynamic and angiographic correlates of low-dose SWMA in patients with chronic ischemic LV systolic dysfunction. Methods: Seventy patients with chronic ischemic LV systolic dysfunction who had dobutamine stress echocardiography were studied. Clinical, hemodynamic, and angiographic parameters at rest and low-dose were compared between 38 patients (mean ejection fraction (EF) of 30 ± 8%) with low-dose SWMA and 32 patients (EF 30 ± 11%) without low-dose SWMA. Results: Multivariate analysis showed that the number of coronary territories with severe disease (stenosis ,70%)(P = 0.001, RR = 6.3) was an independent predictor of low-dose SWMA. An increasing number of collateral vessels protected patients from low-dose SWMA (P = 0.011, RR = 0.25). A higher resting heart rate was a negative predictor of low-dose SWMA (P = 0.015, RR = 0.92) but no other hemodynamic variables were predictors. In the patients with low-dose SMA, regions with low-dose SWMA were more likely to be supplied by vessels with severe disease than regions without low-dose SWMA (92% vs 58%, P < 0.001). Conclusion: In patients with ischemic LV systolic dysfunction, the extent of severe disease and a lower numbers of collaterals predict the occurrence of low-dose SWMA. Low-dose SWMA is a highly specific marker for severe disease. [source]

The DERAA HLA,DR alleles in patients with early polyarthritis: Protection against severe disease and lack of association with rheumatoid arthritis autoantibodies,

ARTHRITIS & RHEUMATISM, Issue 3 2009
Nathalie Carrier
Objective To define the association of alleles encoding the HLA,DR rheumatoid arthritis (RA) protective epitope (DERAA) with the presence of RA-associated antibodies at study inclusion and with severe outcome in patients with early polyarthritis (EPA). Methods Consecutive EPA patients (n = 210) were evaluated early (mean of 4.8 months after diagnosis) and prospectively (for 30 months). HLA class II typing was performed by polymerase chain reaction using sequence-specific primers, and HLA,DR alleles DERAA, RA-associated shared epitope (SE), and non-SE/non-DERAA (neither SE nor DERAA) were identified. RA-associated antibodies identified were anti-Sa/citrullinated vimentin, anti,cyclic citrullinated peptide 2, and IgM rheumatoid factor. Severe disease was defined according to a preset threshold of joint destruction and/or functional limitation. Results DERAA and SE alleles were present in 62 and 110 of the 210 EPA patients, respectively. At 30 months, severe disease was present in 78 patients (37%). In contrast to SE alleles, DERAA alleles were not associated with the production of RA-associated antibodies, but were strongly protective against severe disease at 30 months (odds ratio 0.30, P < 0.001). DERAA alleles emerged as a strong, independent protective marker on multivariate analysis. The protective effect of DERAA was seen only in patients who did not already have erosions at study inclusion, was independent of the presence of antibodies, but was not associated with spontaneous remission. Conclusion In our EPA cohort, the presence of a DERAA sequence was a strong independent predictor of a better prognosis, but only in the absence of erosive disease that was already present at inclusion. Identification of DERAA alleles may help in managing the large subgroup of EPA patients who do not have erosions at baseline. [source]

Relation between stressful life events, neuropeptides and cytokines: results from the LISA birth cohort study

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 8 2008
Gunda Herberth
Stressful life events evidently have an impact on development of allergic diseases, but the mechanism linking stress to pathological changes of immune system function is still not fully understood. The aim of our study was to investigate the relationship between stressful life events, neuropeptide and cytokine concentrations in children. Within the LISAplus (Life style-Immune system-Allergy) study, blood samples from children of 6 yr of age were analysed for concentration of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and the Th1/Th2 cytokines interferon-, (IFN-,) and interleukin (IL)-4. Life events such as severe disease or death of a family member, unemployment or divorce of the parents were assessed with a questionnaire filled in by the parents. For 234 children, blood analysis and questionnaire data regarding life events were available. Children with separated/divorced parents showed high VIP levels and high concentrations of the Th2 cytokine IL-4 in their blood. Severe diseases and death of a family member were neither associated with neuropeptide levels nor with cytokine concentrations. Unemployment of the parents was associated with decreased IFN-, concentrations in children's blood but not with neuropeptide levels, whereas children experiencing concomitant severe disease and death of a family member had reduced SP blood levels. The neuropeptide VIP might be a mediator between stressful life events and immune regulation contributing to the Th2 shifted immune response in children with separated/divorced parents. Unemployment of the parents was associated with immune regulation in children on the basis of a still unknown mechanism whereas reduced SP levels seem to have no effect on immune regulation. [source]

Epidemiology of comorbidities in psoriasis

DERMATOLOGIC THERAPY, Issue 2 2010
Luigi Naldi
ABSTRACT Epidemiological studies have shown that, in patients with psoriasis, associated disorders may occur more frequently than expected. Such comorbidities include, among others, psoriatic arthritis, inflammatory bowel disease, obesity, diabetes, cardiovascular disease, several cancer types, and depression. Comorbidities often become clinically manifest years after onset of psoriasis and tend to be more frequently seen in severe disease. [source]

Stress-Induced Wall Motion Abnormalities with Low-Dose Dobutamine Infusion Indicate the Presence of Severe Disease and Vulnerable Myocardium

Determinants and status of quality of life after long-term botulinum toxin therapy for cervical dystonia

EUROPEAN JOURNAL OF NEUROLOGY, Issue 10 2007
I. M. Skogseid
The aim of this study was to assess health-related quality of life (HRQoL), using the Short Form Health Survey-36 (SF-36), in 70 cervical dystonia (CD) patients after long-term botulinum toxin (BTX) treatment (median 5.5 years), and to identify factors determining reduced HRQoL. We used combined patient-and physician-based measures to assess both CD severity [Toronto Western Spasmodic Torticollis Rating Scale, (TWSTRS)] and effect of long-term BTX treatment, and the Hospital Anxiety and Depression Scale (HAD) and General Health Questionnaire-30 to assess psychological distress. Mean SF-36 domain scores of the CD patients were reduced by <1 SD compared with age- and gender-matched population samples. High TWSTRS total scores and high HAD-depression (HAD-D) scores were the main factors associated with reduced scores in the physical and mental SF-36 domains, respectively. Patients evaluated to have a ,good effect' of long-term BTX treatment (n = 47), had significantly lower median TWSTRS total score, and a 3× lower frequency of high HAD-D scores, than those evaluated to an ,unsatisfactory effect' (n = 23). In conclusion, most CD patients enjoy a good HRQoL after long-term BTX therapy. Reduced HRQoL was associated with more severe disease and/or depressive symptoms. [source]

Reliability and construct validity of the compatible MRI scoring system for evaluation of elbows in haemophilic children

HAEMOPHILIA, Issue 2 2008
A. S. DORIA
Summary., We assessed the reliability and construct validity of the Compatible MRI scale for evaluation of elbows, and compared the diagnostic performance of MRI and radiographs for assessment of these joints. Twenty-nine MR examinations of elbows from 27 boys with haemophilia A and B [age range, 5,17 years (mean, 11.5)] were independently read by four blinded radiologists on two occasions. Three centres participated in the study: (Toronto, n = 24 examinations; Atlanta, n = 3; Cuiaba, n = 2). The number of previous joint bleeds and severity of haemophilia were reference standard measures. The inter-reader reliability of MRI scores was substantial (ICC = 0.73) for the additive (A)-scale and excellent (ICC = 0.83) for the progressive (P)-scale. The intrareader reliability was excellent for both P-scores (ICC = 0.91) and A-scores (ICC = 0.93). The total P- and A-scores correlated poorly (r = 0.36) or moderately (r = 0.54), but positively, with clinical-laboratory measurements. The total MRI scores demonstrated high accuracy for discrimination of presence or absence of arthropathy [P-scale, area-under-the-curve (AUC) = 0.94 ± 0.05; A-scale, AUC = 0.89 ± 0.06], as did the soft tissue scores of both scales (P-scale, AUC = 0.90 ± 0.06; A-scale, AUC = 0.86 ± 0.06). Areas-under-the-curve used to discriminate severe disease demonstrated high accuracy for both P-MRI scores (AUC = 0.83 ± 0.09) and A-MRI scores (AUC = 0.87 ± 0.09), but non-diagnostic ability to discriminate mild disease. Similar results were noted for radiographic scales. In conclusion, both MRI scales demonstrated substantial to excellent reliability and accuracy for discrimination of presence/absence of arthropathy, and severe/non-severe disease, but poor to moderate convergent validity for total scores and non-diagnostic discriminant validity for mild/non-mild disease. Compared with radiographic scores, MRI scales did not perform better for discrimination of severity of arthropathy. [source]

A global view on prophylaxis: possibilities and consequences

HAEMOPHILIA, Issue 2003
A. D. Shapiro
Summary., Prophylactic infusion therapy, both primary and secondary, has proven of great benefit to patients with haemophilia, specifically those with severe disease or bleeding episodes and patterns that have lead to development of arthropathy. At this time, optimal outcome in patients with severe haemophilia has been proven achievable with primary prophylaxis initiated at an early age in a regimen of three times weekly or every other day for patients with factor VIII deficiency, and twice weekly for those with factor IX deficiency. Despite the demonstrated benefit of primary prophylaxis, this treatment regimen has not been uniformly adopted into clinical practice even in developed countries. In developing countries, where issues of allocation of precious health care resources are of paramount importance, access to adequate treatment for persons with haemophilia on a programme of on-demand therapy is not commonly available; the cost of primary prophylaxis, even with intermediate purity plasma-derived factor concentrates or plasma fractions such as cryoprecipitate, renders this treatment the exception rather than the rule. [source]

Long-term exclusive zinc monotherapy in symptomatic Wilson disease: Experience in 17 patients,

HEPATOLOGY, Issue 5 2009
Francisca H. H. Linn
Exclusive monotherapy with zinc in symptomatic Wilson disease is controversial. Seventeen symptomatic patients with Wilson disease were treated with zinc only. The mean age at diagnosis and start of treatment was 18 years (range 13,26) with approximately half presenting as adolescents. Presentation was exclusively hepatic, exclusively neurologic, and combined in seven, five, and five patients, respectively. The median follow-up was 14 years (range 2,30). At baseline, two of the 12 patients with hepatic disease exhibited decompensated cirrhosis, five exhibited compensated cirrhosis, and five had less severe disease. Both patients with decompensated cirrhosis improved to a compensated state after initiation of therapy. Two of the five patients with initial compensated cirrhosis progressed to decompensated state, and three remain stable. Three of the five patients with moderate or mild liver disease remain stable and two improved. Apart from decreasing bilirubin levels, no significant changes occurred in the liver biochemistry or function during long-term follow-up. Nine of 10 neurologic patients improved markedly and one deteriorated. Two patients with exclusively neurologic presentation developed liver disease during zinc treatment. Two patients with exclusively hepatic presentation developed mild neurologic symptoms. According to 24-hour urinary copper excretions (213 ± 38 versus 91 ± 23 ,g: P = 0.01) and serum non,ceruloplasmin-bound copper concentrations (11 ± 2 versus 7 ± 1 ,g/dL: P = 0.1) at the end of follow-up, the efficacy of decoppering was less in the exclusively hepatic than in the neurologic group. The prescribed zinc dose and 24-hour urinary zinc excretions tended to be less in the exclusively hepatic group. Conclusion: The outcome of exclusive zinc therapy is generally good in cases of neurologic disease. A less satisfactory outcome in hepatic disease may relate to less efficient decoppering. (HEPATOLOGY 2009.) [source]

Influence of ursodeoxycholic acid on the mortality and malignancy associated with primary biliary cirrhosis: A population-based cohort study,

HEPATOLOGY, Issue 4 2007
Hannah Jackson
There is debate over the mortality and malignancy risk in people with primary biliary cirrhosis (PBC) and whether this risk is reduced by use of ursodeoxycholic acid. To investigate this issue, we identified 930 people with PBC and 9,202 control subjects from the General Practice Research Database in the United Kingdom. We categorized regular ursodeoxycholic acid as treatment with 6 or more prescriptions and nonregular treatment as less than 6. We found a 2.7-fold increase in mortality for the PBC cohort compared with the general population [adjusted hazard ratio (HR), 2.69; 95% CI, 2.35,3.09]. In those having regular ursodeoxycholic acid (43%), the mortality increase was 2.2-fold (HR, 2.19; 95% CI, 1.66,2.87) and in those not treated 2.7-fold (HR, 2.69; 95% CI, 2.18,3.33). This apparent reduction in mortality was not explained by less severe disease in the ursodeoxycholic acid,treated group. The increased risk of primary liver cancer in ursodeoxycholic acid,treated patients was 3-fold (HR, 3.17; 95% CI, 0.64,15.62), in contrast to an 8-fold increase in those not treated (HR, 7.77; 95% CI, 1.30,46.65). Conclusion: We found that people with PBC had a 3-fold mortality increase when compared with the general population, which was somewhat reduced by regular treatment with ursodeoxycholic acid. However, the observed effect of ursodeoxycholic acid was not statistically significant. (HEPATOLOGY 2007.) [source]

Induction of the vascular endothelial growth factor pathway in the brain of adults with fatal falciparum malaria is a non-specific response to severe disease

HISTOPATHOLOGY, Issue 2 2010
Isabelle M. Medana
Medana I M, Day N P J, Roberts R, Sachanonta N, Turley H, Pongponratn E, Hien T T, White N J. & Turner G D H (2010) Histopathology,57, 282,294 Induction of the vascular endothelial growth factor pathway in the brain of adults with fatal falciparum malaria is a non-specific response to severe disease Aims:, Pathological or neuroprotective mechanisms in the brain in severe malaria may arise from microvascular obstruction with malaria-parasitized erythrocytes. This study aimed to investigate the role of hypoxia and induction of the vascular endothelial growth factor (VEGF) pathway in the neuropathophysiology of severe malaria. Methods and results:, Immunohistochemistry was performed on post mortem brain tissue sections from 20 cases of severe malaria and examined for the expression of transcriptional regulators of VEGF [hypoxia-inducible factor-1 alpha (HIF-1,), HIF-2,], DEC-1, VEGF, VEGF receptors 1 and 2, and the activated, phosphorylated VEGF receptor 2 (pKDR). HIFs showed limited protein expression and/or translocation to cell nuclei in severe malaria, but DEC-1, which is more stable and regulated by HIF-1,, was observed. There was heterogeneous expression of VEGF and its receptors in severe malaria and non-malarial disease controls. pKDR expression on vessels was greater in malaria cases than in controls but did not correlate with parasite sequestration. VEGF uptake by malaria parasites was observed. Conclusions:, VEGF and its receptor expression levels in severe malaria reflect a non-specific response to severe systemic disease. Potential manipulation of events at the vasculature by the parasite requires further investigation. [source]

DMD exon 1 truncating point mutations: Amelioration of phenotype by alternative translation initiation in exon 6,

HUMAN MUTATION, Issue 4 2009
Olga L. Gurvich
Abstract Mutations in the DMD gene result in two common phenotypes associated with progressive muscle weakness: the more severe Duchenne muscular dystrophy (DMD) and the milder Becker muscular dystrophy (BMD). We have previously identified a nonsense mutation (c.9G>A; p.Trp3X) within the first exon of the DMD gene, encoding the unique N-terminus of the 427-kDa muscle isoform of the dystrophin protein. Although this mutation would be expected to result in severe disease, the clinical phenotype is very mild BMD, with ambulation preserved into the seventh decade. We identify the molecular mechanism responsible for the amelioration of disease severity to be initiation of translation at two proximate AUG codons within exon 6. Analysis of large mutational data sets suggests that this may be a general mechanism of phenotypic rescue for point mutations within at least the first two exons of the DMD gene. Our results directly demonstrate, for the first time, the use of alternate translational initiation codons within the DMD gene, and suggest that dystrophin protein lacking amino acids encoded by the first five exons retains significant function. Hum Mutat 0:1,8, 2009. © 2009 Wiley-Liss, Inc. [source]

The immunobiology of Th1 polarization in high-pathology schistosomiasis

IMMUNOLOGICAL REVIEWS, Issue 1 2004
Miguel J. Stadecker
Summary:, Schistosomiasis is a serious global helminthic disease, in which the main immunopathology consists of a granulomatous and fibrosing reaction against tissue-trapped parasite eggs. The severity of this inflammatory process, the product of a CD4+ T-cell-mediated immune response against parasite egg antigens, is, however, markedly uneven, both in human patients and among mouse strains in an experimental model. Severe schistosomiasis is associated with persistently elevated pro-inflammatory T-helper-1 (Th1)-type cytokines, whereas milder pathology is present when Th2 cytokines dominate. This scenario is supported by the pronounced pathology resulting from the obliteration of pathways that facilitate Th2 differentiation and by the development of more intense lesions in mouse strains that fail to downregulate the Th1 response. Genetically prone high-pathology mice have a higher proportion of CD4+ T cells in lymph nodes and granulomas, in which the Th1 phenotype is driven by interleukin-12; they also develop a dominant repertoire against peptide 234,246 of the major Sm-p40 egg antigen, utilizing a strikingly restricted T-cell receptor structure that involves V,11.3,8. In turn, low-pathology mice exhibit enhanced CD4+ T-cell apoptosis, which contributes to limit pathology. The definition of distinctive immune profiles associated with polar forms of schistosomiasis opens opportunities for targeted immuno-intervention in individuals suffering from or at risk of severe disease. [source]

Cytomegalovirus in inflammatory bowel disease: Pathogen or innocent bystander?

INFLAMMATORY BOWEL DISEASES, Issue 9 2010
Garrett Lawlor MD
Abstract The role of cytomegalovirus (CMV) in exacerbations of inflammatory bowel disease (IBD) remains a topic of ongoing debate. Current data are conflicting as to whether CMV worsens inflammation in those with severe colitis, or is merely a surrogate marker for severe disease. The interpretation of existing results is limited by mostly small, retrospective studies, with varying definitions of disease severity and CMV disease. CMV colitis is rare in patients with Crohn's disease or mild-moderate ulcerative colitis. In patients with severe and/or steroid-refractory ulcerative colitis, local reactivation of CMV can be detected in actively inflamed colonic tissue in about 30% of cases. Where comparisons between CMV+ and CMV, steroid-refractory patients can be made, most, but not all, studies show no difference in outcomes according to CMV status. Treatment with antiviral therapy has allowed some patients with severe colitis to avoid colectomy despite poor response to conventional IBD therapies. This article reviews the immunobiology of CMV disease, the evidence for CMV's role in disease severity, and discusses the outcomes with antiviral therapy. (Inflamm Bowel Dis 2010) [source]

Ulcerative colitis: Correlation of the Rachmilewitz endoscopic activity index with fecal calprotectin, clinical activity, C-reactive protein, and blood leukocytes

INFLAMMATORY BOWEL DISEASES, Issue 12 2009
Alain M. Schoepfer MD
Abstract Background: The accuracy of noninvasive markers for the detection of endoscopically active ulcerative colitis (UC) according the Rachmilewitz Score is so far unknown. The aim was to evaluate the correlation between endoscopic disease activity and fecal calprotectin, Clinical Activity Index, C-reactive protein (CRP), and blood leukocytes. Methods: UC patients undergoing colonoscopy were prospectively enrolled and scored independently according the endoscopic and clinical part of the Rachmilewitz Index. Patients and controls provided fecal and blood samples for measuring calprotectin, CRP, and leukocytes. Results: Values in UC patients (n = 134) compared to controls (n = 48): calprotectin: 396 ± 351 versus 18.1 ± 5 ,g/g, CRP 16 ± 13 versus 3 ± 2 mg/L, blood leukocytes 9.9 ± 3.5 versus 5.4 ± 1.9 g/L (all P < 0.001). Endoscopic disease activity correlated closest with calprotectin (Spearman's rank correlation coefficient r = 0.834), followed by Clinical Activity Index (r = 0.672), CRP (r = 0.503), and leukocytes (r = 0.461). Calprotectin levels were significantly lower in UC patients with inactive disease (endoscopic score 0,3, calprotectin 42 ± 38 ,g/g), compared to patients with mild (score 4,6, calprotectin 210 ± 121 ,g/g, P < 0.001), moderate (score 7,9, calprotectin 392 ± 246 ,g/g, P = 0.002), and severe disease (score 10,12, calprotectin 730 ± 291 ,g/g, P < 0.001). The overall accuracy for the detection of endoscopically active disease (score ,4) was 89% for calprotectin, 73% for Clinical Activity Index, 62% for elevated CRP, and 60% for leukocytosis. Conclusions: Fecal calprotectin correlated closest with endoscopic disease activity, followed by Clinical Activity Index, CRP, and blood leukocytes. Furthermore, fecal calprotectin was the only marker that reliably discriminated inactive from mild, moderate, and highly active disease, which emphasizes its usefulness for activity monitoring. Inflamm Bowel Dis 2009 [source]

Active Crohn's disease and ulcerative colitis can be specifically diagnosed and monitored based on the biostructure of the fecal flora

INFLAMMATORY BOWEL DISEASES, Issue 2 2008
Alexander Swidsinski MD
Abstract Background: The intestinal microflora is important in the pathogenesis of inflammatory bowel disease (IBD). The impact of its spatial organization on health and disease is unknown. Methods: We investigated sections of paraffin-embedded punched fecal cylinders. Fluctuations in spatial distribution of 11 bacterial groups were monitored in healthy subjects (n = 32), patients with IBD (n = 204), and other gastrointestinal diseases (n = 186) using fluorescence in situ hybridization (FISH). Results: The microbial structure differed in patients with Crohn's disease (CD), ulcerative colitis (UC), and healthy and disease controls. The profiles of CD and UC were distinctly opposite in 6 of 11 FISH probes used. Most prominent were a depletion of Faecalibacterium prausnitzii (Fprau<1 × 109/mL) with a normal leukocyte count in CD and a massive increase of leukocytes in the fecal-mucus transition zone (>30 leukocytes/104,m2) with high Fprau in patients with UC. These 2 features alone enabled the recognition of active CD (Crohn's Disease Activity Index [CDAI] >150) or UC (Clinical Activity Index [CAI] >3) with 79%/80% sensitivity and 98%/100% specificity. The mismatch in the sensitivity was mainly due to overlap between single IBD entities, and the specificity was exclusively due to the similarity of Crohn's and celiac disease. When inflammatory bowel disease (IBD) patients were pooled the sensitivity was 100% for severe disease, 84% for moderate activity, 72% for IBD with ,12 months remission, and 24% for IBD with >12 months remission. Conclusions: The fecal flora is highly structured and spatially organized. Diagnosing IBD and monitoring disease activity can be performed based on analysis of punched fecal cylinders independent from the patient's complaints. (Inflamm Bowel Dis 2007) [source]

Genotype-phenotype analysis in childhood-onset Crohn's disease: NOD2/CARD15 variants consistently predict phenotypic characteristics of severe disease

INFLAMMATORY BOWEL DISEASES, Issue 11 2005
Richard K Russell
Abstract Introduction: The incidence of early-onset CD in Scotland is among the highest worldwide. Three single nucleotide polymorphisms (SNPs) R702W, G908R and Leu1007finsC in the NOD2/CARD15 gene predispose to adult CD. We investigated the contribution of these variants to disease susceptibility and phenotype in the Scottish early-onset IBD population. Patients and Methods: 906 individuals including 247 Scottish IBD patients aged <16 years at diagnosis, 414 parents and 245 controls were genotyped. Transmission disequilibrium testing (TDT), case-control analysis and detailed genotype-phenotype analysis were performed. Results: The Leu1007finsC variant was associated with susceptibility to CD by case-control (4.2% versus. 1.4%, P = 0.01) and TDT analysis (P = 0.006). The Population Attributable Risk (PAR) for the 3 NOD2/CARD15 mutations was 7.9%. Carriage of NOD2/CARD15 variants was associated with, at diagnosis: decreased albumin (31.0% versus. 9.0%, P = 0.001) and raised CRP (25% versus. 9.5%, P = 0.04) and at follow up: need for surgery (39.5% versus. 12.8%, P = 0.0002) jejunal involvement (50% versus. 18.4%, P = 0.01) jejunal and ileal involvement (50% versus. 10.7%, P = 0.009), raised CRP (57.1% and 12.8%, P = 0.0009), lower weight/height centile (75.0% versus. 20.2%, P = 0.03, 50.0% versus. 16.0%, P = 0.001 respectively) and stricturing disease (45.5% versus. 19.4%, P < 0.05). Multifactorial analysis demonstrated carriage was associated with need for surgery (P = 0.004, OR 4.9 [1.5-14.7]). Conclusions: These NOD2/CARD 15 variants in the Scottish early onset CD population have a definite, albeit relatively small contribution to CD susceptibility (PAR 7.9%) but a major impact on phenotype. In particular NOD2/CARD15 variants are strongly associated with several markers of disease severity in pediatric CD, notably need for surgery. [source]

Azathioprine or 6-mercaptopurine before colectomy for ulcerative colitis is not associated with increased postoperative complications

INFLAMMATORY BOWEL DISEASES, Issue 5 2002
Uma Mahadevan
Abstract Aim To determine whether the use of azathioprine/6-mercaptopurine before colectomy is associated with an increased rate of postoperative complications. Methods All patients who underwent colectomy with ileal pouch,anal anastomosis for ulcerative colitis between 1997 and 1999 were identified. Medical records were abstracted for demographics, extent and duration of disease, dose and duration of corticosteroids and azathioprine/6-mercaptopurine, albumin, and Truelove/Witts score. Early (30-day) and late (6-month) complications were identified. Noncorticosteroid immunosuppressive use was coded as none, azathioprine/6-mercaptopurine within 1 week of surgery, or therapy with other immunosuppressive agents within 1 month of surgery. A logistic regression analysis assessed the association between these variables and complications. Results Early complications occurred in 49 of 151 (32%) patients not treated with immunosuppressive agents, 12 of 46 (26%) azathioprine/6-mercaptopurine-treated patients, and 4 of 12 (33%) patients treated with other immunosuppressive agents (p = 0.71). Late complications occurred in 72 of 148 (49%), 20 of 46 (43%), and 8 of 12 (67%) patients in these same groups, respectively. Intravenous or oral steroids at doses of 40 mg/d or greater (p < 0.01) and severe or fulminant disease (p = 0.0094) were associated with greater early complication rates. Conclusion Early complications after restorative proctocolectomy for ulcerative colitis are associated with high dose steroids and severe disease but not use of azathioprine/6-mercaptopurine. [source]

Un-promoted issues in inflammatory bowel disease: opportunities to optimize care

INTERNAL MEDICINE JOURNAL, Issue 3 2010
J. M. Andrews
Abstract Inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the gut, which lead to significant morbidity and impaired quality of life (QoL) in sufferers, without generally affecting mortality. Despite CD and UC being chronic, life-long illnesses, most medical management is directed at acute flares of disease. Moreover, with more intensive medical therapy and the development of biological therapy, there is a risk that management will become even more narrowly focused on acute care, and be directed only at those with more severe disease, rather than encompassing all sufferers and addressing important non-acute issues. This imbalance of concentration of medical attention on ,high-end' care is in part driven by the need to perform and publish randomized clinical trials of newer therapies to obtain registration and licensing for these agents, which thus occupy a large proportion of the recent IBD treatment literature. This leads to less attention on relatively ,low-technology' issues including: (i) the psychosocial burden of chronic disease, QoL and specific psychological comorbidities; (ii) comorbidity with functional gastrointestinal disorders (FGIDs); (iii) maintenance therapy, monitoring and compliance; (iv) smoking (with regard to CD); (v) sexuality, fertility, family planning and pregnancy; and (vi) iron deficiency and anaemia. We propose these to be the ,Un-promoted Issues' in IBD and review the importance and treatment of each of these in the current management of IBD. [source]

Association between a common IL10 distal promoter haplotype and IgE production in individuals with atopic dermatitis

INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4 2009
K. Lacy
Summary Atopic dermatitis (AD) is a genetically determined inflammatory skin disease characterized by abnormal cytokine production, including increased production of interleukin 10 (IL10). Single nucleotide polymorphisms (SNP) and haplotypes in the IL10 gene promoter region on chromosome 1q31-32 have been implicated in several inflammatory diseases, but generally, only SNPs proximal to the transcription start site (TSS) have been investigated. The aim of this study was to identify proximal, distal and combined haplotype sets in the IL10 promoter region and to study their association with clinical phenotypes in atopic dermatitis. SNPs at positions ,3575, ,2849, ,2779, ,2763, ,1082, ,851, ,819 and ,592 in the IL10 promoter region were genotyped in individuals with atopic dermatitis (n= 47) and nonatopic control subjects (n= 40) using polymerase chain reaction-based techniques and induced heteroduplex generator (IHG) analysis. Pan-promoter, TSS-proximal and TSS-distal haplotypes were reconstructed using phase analysis. Fifteen haplotypes representing all eight SNPs were identified. Subgrouping identified four 4-locus and three 3-locus TSS-proximal haplotypes; and nine 4-locus TSS-distal haplotypes. No difference was found in haplotype or SNP frequencies between the AD and control groups, or between patients with mild or severe disease. However, a common 4-locus TSS-distal haplotype (TGAC) was significantly increased in patients with IgE levels over 1000 kIU L,1. This study is the first to analyse the association between haplotype groups in the IL10 promoter region and clinical phenotypes in AD. We have demonstrated a significant association between the TSS-distal haplotype TGAC, and IgE levels in AD patients. It remains to be shown if there is an association between the TGAC haplotype and IL10 production, which might account for the stimulation of IgE production. [source]

New media for the semiselective isolation and enumeration of Xanthomonas campestris pv. mangiferaeindicae, the causal agent of mango bacterial black spot

JOURNAL OF APPLIED MICROBIOLOGY, Issue 4 2005
O. Pruvost
Abstract Aims:, Mango bacterial black spot, caused by Xanthomonas campestris pv. mangiferaeindicae, is a potentially severe disease in several tropical and subtropical areas. Data describing the life cycle of the pathogen are needed for improving integrated pest management strategies. Because of the important bacterial microflora associated with mango leaves, isolation of the pathogen is often difficult using nonselective agar media. Methods and Results:, A previously developed medium, BVGA, failed to inhibit several Gram-negative saprophytic bacteria, especially those belonging to Enterobacteriaceae. Two new semiselective media were developed. The selectivity of KC and NCTM3 media was achieved using cephalexin 40 mg l,1, kasugamycin 20 mg l,1 and neomycin 1 mg l,1, cephalexin 100 mg l,1, trimethoprime 5 mg l,1, pivmecillinam 100 mg l,1 respectively. Plating efficiencies ranged from 76 to 104% and from 78 to 132% for KC and NCTM3 respectively. Conclusions:, The new media allowed the growth of X. campestris pv. mangiferaeindicae whatever its country of isolation. The pathogen was repeatedly isolated with these media from asymptomatic leaves sampled in growth chamber experiments. Significance and Impact of the Study:, This work provides a description of new semiselective media, which should be valuable tools to study the ecology and epidemiology of X. campestris pv. mangiferaeindicae. [source]

Is the Prevalence of Paget's Disease of Bone Decreasing?,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue S2 2006
Tim Cundy
Abstract Secular trends in the severity and prevalence of Paget's disease over a 30-year period are described. Paget's disease has become less prevalent and patients are presenting later, with less severe disease than previously. These data suggest that environmental factors are important in the etiology of Paget's disease. Introduction: Data from several countries support the view that there are important secular trends in the prevalence and severity of Paget's disease. In this paper, recent trends in the epidemiology of Paget's disease are described. Materials and Methods: A database of all newly referred patients (n = 1487) with Paget's disease (1973,2002 inclusive, 30 years) was examined. Of these subjects, 56% had scintiscans. Plasma total alkaline phosphatase (total ALP) activity and disease extent on scintiscan were used as indices of severity. A radiographic prevalence survey of 1019 subjects of European origin >55 years of age in Dunedin was undertaken,,20 years after an earlier survey had shown New Zealand to be a high prevalence area. Results: The number of new referrals with Paget's disease declined sharply from 1994 onward, to one half the rate seen 20 years earlier, whereas the mean age at presentation increased by 4 years per decade (p < 0.0001). Total ALP at diagnosis, disease extent on scintiscan, and the number of bones involved were all negatively correlated with both date of birth (p < 0.0001) and year of presentation (p < 0.0001), indicating that more recently born and presenting subjects had substantially less severe bone disease. The radiographic survey showed that the current prevalence was only ,50% of that in the 1983 survey (p = 0.012). Conclusions: Although there are a number of potential biases, these data are consistent with a continued secular trend to presentation in older subjects with less extensive skeletal involvement and a declining prevalence of Paget's disease. [source]

Prevalence of high antibody titers of pertussis in Turkey: reflection of circulating microorganism and a threat to infants

JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2007
Berrin Esen
Abstract Acute pertussis infection among adults can cause its transmission to the larger population, especially to infants and young children, who can develop severe disease. In order to determine an age-dependent pertussis immune response, anti-pertussis toxin (PT) antibody was detected by the indirect enzyme-linked immunosorbent assay (ELISA) method in serum samples from 2,085 healthy subjects ranging in age from 6 months to ,60 years. Also included in the evaluation were responses to a questionnaire including sociodemographic characteristics, vaccination, and infection history. Titers of 50,99 ELISA units (EU)/mL and of ,100,EU/mL were accepted as indicative for recent exposure or infection. In addition, 30,EU/mL was estimated to be a sufficient titer in women of childbearing age to protect their newborns until administration of their first dose of pertussis vaccine. After the age of 4,5 years, presence of high-titered antibodies that increase with age might be a reflection of circulating infection and indicate the magnitude of the threat to infants. According to the questionnaires, in the groups younger than 15 years old, three to four doses of diphtheria toxoid-whole cell pertussis-tetanus toxoid (DwPT) were administered in 47.2 to 77.4%, 91.2 to 100.0%, and 83.5 to 100.0% of participants in Diyarbakir, Samsun, and Antalya, respectively. In addition, up to half of the expectant mothers we studied lacked a sufficient level of estimated antibody titers. To protect infants from life-threatening pertussis infection, improving vaccination coverage to ensure herd immunity and uniformly establishing coverage throughout the country are essential. Furthermore, revaccination with acellular vaccine for schoolchildren as well as for the households of pregnant women is recommended. J. Clin. Lab. Anal. 21:154,161, 2007. © 2007 Wiley-Liss, Inc. [source]

Superficial femoral artery occlusive disease severity correlates with MR cine phase-contrast flow measurements

JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 3 2006
Kiyarash Mohajer MD
Abstract Purpose To evaluate how cine phase-contrast (PC) flow data correlate with the severity of peripheral vascular disease (PVD). Materials and Methods Flow waveforms were obtained in 48 patients proximal and distal to superficial femoral artery (SFA) disease using the 2D cine PC technique with velocity encoding (venc) = 100 cm/second. Flow data were correlated with SFA disease severity and compared with data from nine healthy volunteers. Results Of 96 arterial segments in 48 patients, 26 were patent or only mildly stenotic, 35 had moderate-to-severe stenosis, and 35 were occluded. The flow patterns tended to become low-resistant below severe stenoses or occlusion. The mean peak flow velocity above/below SFA lesions was significantly higher in patients with severe disease (1.9 ± 1.0, P = 0.01) or occlusion (2.0 ± 1.0, P = 0.003) compared to normal volunteers (1.4 ± 0.6). The delay in peak velocity below the lesions showed a significant positive correlation with lesion severity (r = 0.65, P < 0.001). The mean flow volume ratio above/below SFA lesions was greater in patients with occluded vessels compared to normal volunteers (3.9 and 2.3 respectively; P = 0.04). Conclusion Cine PC flow waveform changes across atherosclerotic lesions correlate with disease severity. This may help determine which lesions are hemodynamically significant. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc. [source]

Comparison of viral load and duration of virus shedding in symptomatic and asymptomatic neonatal rotavirus infections

JOURNAL OF MEDICAL VIROLOGY, Issue 10 2010
Sasirekha Ramani
Abstract A single rotavirus strain causing asymptomatic infections as well as severe gastrointestinal disease has been described in the neonatal nurseries of the Christian Medical College, Vellore. In this study, quantitative real-time RT-PCR was used to determine the association of viral load with the presence of gastrointestinal symptoms in neonates. Viral load was estimated in terms of the crossing point [C(t) value] at which the amplicon could be detected in the real-time PCR assay. The study was carried out on 103 neonates, including 33 asymptomatic neonates and 70 neonates with different gastrointestinal symptoms. The duration of virus shedding was also compared between five symptomatic and four asymptomatic neonates using real-time RT-PCR. There was no significant difference in viral load between symptomatic and asymptomatic neonates (P,=,0.087). Among neonates with different gastrointestinal symptoms, those presenting with feed intolerance and abdominal distension had a significantly higher viral load than those with other gastrointestinal symptoms (P,=,0.02). For the study on virus shedding, nine neonates were followed up for a median duration of 53 days, with a median of 31 samples tested per child. Extended shedding of low copies of rotavirus was found, with no significant differences in pattern of shedding between symptomatic and asymptomatic neonates. The lack of correlation between viral load and gastrointestinal disease demonstrates yet another difference between neonatal rotavirus infection and infection in older children where higher viral load correlates with severe disease. J. Med. Virol. 82:1803,1807, 2010. © 2010 Wiley-Liss, Inc. [source]

Hepatitis E in Qatar imported by expatriate workers from Nepal: Epidemiological characteristics and clinical manifestations

JOURNAL OF MEDICAL VIROLOGY, Issue 6 2009
Abdulsalam Saif Ibrahim
Abstract Prompted by cases of acute hepatitis in expatriate workers presenting at Alkhor Hospital, Qatar, a limited prospective observational study was conducted from July 2005 to June 2006 to determine the epidemiological and clinical features of patients (predominantly Nepalese) presenting with acute hepatitis. Countrywide during that period samples from 86 Nepalese presenting at different centers were found to be anti-HEV IgG positive and 50 of these were also positive for anti-HEV IgM. Fifty-eight of those Nepalese were seen and treated at Alkhor Hospital and of them 43 were confirmed as cases of acute HEV, being positive for both anti-HEV IgM and IgG. The remaining 15 were diagnosed as probable cases of acute HEV on the basis of clinical and epidemiological similarity. It seems likely that transit in Kathmandu in reportedly unsanitary conditions was the focus of infection. In some of those examined at Alkhor, ultrasound detected a thickened gallbladder wall in 30 of 39 (76.9%) with two cases having clinical acalcular cholecystitis. Higher levels of alanine aminotransferase and aspartate aminotransferase were associated with severe disease and derangement in coagulation. On the available evidence hepatitis E was imported by expatriate workers and it is clear that medical screening of these workers pre- and post-arrival must be improved to prevent further outbreaks. It is also essential that health care workers in Qatar are made aware of this ongoing problem of imported HEV and understand the variable presentation of the condition. J. Med. Virol. 81:1047,1051, 2009. © 2009 Wiley-Liss, Inc. [source]

Morbidity and mortality associated with pre-eclampsia at two tertiary care hospitals in Sri Lanka

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2007
Vajira H. W. Dissanayake
Abstract Aim:, To report the occurrence of morbidity and mortality associated with carefully phenotyped pre-eclampsia in a sample of nulliparous Sinhalese women with strictly defined disease. Methods:, A phenotyping database of 180 nulliparous women with pre-eclampsia and 180 nulliparous normotensive pregnant women who were recruited for a study into genetics of pre-eclampsia was analyzed. Results:, Women who developed pre-eclampsia had significantly higher systolic blood pressure (SBP; P = 0.002) and diastolic blood pressure (DBP; P = 0.002) at booking (at approximately 13 weeks of gestation). 38.3%, 28.3% and 33.3% of women delivered at <34 weeks, at 34,36 weeks, and at term, respectively. 78% required a cesarean section. Complications included SBP , 160 mmHg (75.5%); DBP , 110 mmHg (83.8%); proteinuria ,3 + (150 mg/dL) in the urine protein heat coagulation test (87%); renal failure requiring dialysis (2%); platelet counts <100 × 109/L (13%); ,70 U/L in aspartate and/or alanine aminotransaminase (15%); placental abruption (4%); eclampsia (9%); and one maternal death. Maternal complications indicative of severe disease, apart from the incidence of SBP , 160 mmHg and DBP , 110 mmHg, were not significantly different in early and late-onset pre-eclampsia; fetal outcome was better with late-onset disease. 48% of babies were small for gestational age. Only 80 of 135 babies of women with pre-eclampsia whose condition could be confirmed at 6 weeks post-partum were alive. Conclusions:, Pre-eclampsia in Sinhalese women is associated with severe maternal morbidity and fetal morbidity and mortality, suggesting that modification of the Western diagnostic criteria and/or guidelines for medical care may be necessary. There is an urgent need to improve neonatal intensive care services in Sri Lanka. [source]

Infection of Blackcurrant Leaves by Drepanopeziza ribis in Relation to Weather Conditions and Leaf Position

JOURNAL OF PHYTOPATHOLOGY, Issue 5 2009
Xiang Ming Xu
Abstract Drepanopeziza ribis causes the leaf spot disease of blackcurrant (Ribes nigrum) and may lead to severe premature leaf-fall. Artificial inoculation studies were carried out to investigate infection of leaves by D. ribis conidia in relation to environmental conditions and leaf position (age) on cvs. Baldwin and Ben Hope in April and July 2007. All leaves on a number of selected extension shoots on potted three-year old plants were inoculated with conidia and then incubated under different conditions: 10, 17.5 and 25°C each with five wet periods (4, 8, 12, 24 and 30 h). Number of infected leaves was determined. The two cultivars differed significantly in their susceptibility to conidial infection: cv. Baldwin was much more susceptible than cv. Ben Hope. Older leaves on extension shoots were more susceptible to conidial infection than younger leaves. Increasing length of wetness duration led to increasing incidence of leaves infected, particularly when inoculated in July. However, the effects of temperature were inconclusive and generally very small in comparison with other factors. Field epidemics were monitored over three years (2005,07). Field data confirmed the main findings from controlled inoculation studies: severe disease was associated with very wet conditions and older leaves. Furthermore, they also suggested that significant disease increase only occurred from late July onwards. [source]

Detection of Phytoplasma Infection in Rose, with Degeneration Symptoms

JOURNAL OF PHYTOPATHOLOGY, Issue 1 2001
M. Kami
In 1998 a severe disease was observed on rose cvs. ,Patina', ,Papillon' and ,Mercedes' cultivated in a commercial greenhouse in Poland. The symptoms included stunted growth, bud proliferation, leaf malformation and deficiency of flower buds. Sporadically some plants yielded flower buds transformed into big-bud structures and degenerated flowers. The presence of phytoplasma in roses with severe symptoms as well as in recovered plants and Catharanthus roseus experimentally infected by grafting and via dodder was demonstrated by nested polymerase chain reaction assay with primers pair R16F2/R2 or R16F1/R0 and R16(I)F1/R1 amplifying phytoplasma 16S rDNA fragment. The polymerase chain reaction products (1.1 kb) used for restriction fragment length polymorphism analysis after digestion with endonuclease enzymes AluI and MseI produced the same restriction profiles for all samples. The restriction profiles of phytoplasma DNA from these plants corresponded to those of an aster yellows phytoplasma reference strain. Electron microscope examination of the ultra-thin sections of the stem showed wall thickenings of many sieve tubes of the diseased roses and single phytoplasma cells within a sieve element of the phloem of experimentally infected periwinkles. This paper is the first report on aster yellows phytoplasma in rose identified at a molecular level. Detektion einer Phytoplasma-Infektion bei Rosen mit Degenerationserscheinungen Im Jahr 1998 wurde eine schwere Krankheit bei Rosen der Sorten ,Patina', ,Papillon' und ,Mercedes' festgestellt, die in einem polnischen Gewächshaus für kommerzielle Zwecke kultiviert wurden. Zu den Symptomen gehörten Kümmerwuchs, durchwachsene Knospen, Blattmißbildungen und ein Mangel an Blütenknospen. Einige wenige Pflanzen trugen übergroße Blütenknospen, die degenerierte Blüten hervorbrachten. Die Anwesenheit von Phytoplasmen in Rosen mit starken Symptomen, in erholten Pflanzen und in Catharanthus roseus, der durch Pfropfen und durch Teufelszwirn (Cuscuta) experimentell infiziert worden war, wurde mittels einer genesteten Polymerase-Kettenreaktion mit den Primerpaaren R16F2/R2 oder R16F1/R0 und R16(1)F1/R1 zur Amplifikation des Phytoplasma-16S rDNA-Fragments demonstriert. Die für die Analyse der Restriktionsfragmentlängenpolymorphismen nach Verdau mit den Endonucleasen AluI und MseI verwendeten PCR-Produkte (1,1 kb) produzierten bei allen Proben die gleichen Restriktionsprofile. Die Restriktionsprofile der Phytoplasma-DNA aus diesen Pflanzen entsprachen denjenigen eines Typenstamms eines Asternvergilbung auslösenden Phytoplasmas. Elektronenmikroskopische Untersuchungen ultradünner Schnitte des Stamms zeigten Wandverdickungen bei zahlreichen Siebröhren der erkrankten Rosen und einzelne Phytoplasmazellen innerhalb eines Siebelements des Phloems experimentell infizierter Immergrün-Pflanzen. Dies ist der erste Bericht über ein auf molekularer Ebene identifiziertes Asternvergilbungs-Phytoplasma bei Rosen. [source]

Combining etanercept with traditional agents in the treatment of psoriasis: a review of the clinical evidence

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2010
PA Foley
Abstract Psoriasis is a chronic, systemic inflammatory disorder manifesting primarily in skin and potentially in joints, frequently necessitating treatment with conventional systemic therapies, phototherapy or biological agents. Patients with moderate to severe disease suffer a diminished quality of life, experience significant comorbidities and have a higher mortality. Although traditional treatments are effective in the short-term, their use is often limited by concerns over long-term toxicity, including end-organ damage and risk of malignancy. Combination therapy is a commonly used approach and is often more effective than any single agent. Lower doses of two treatments in combination can also minimize potential side effects from a single agent at higher doses. Etanercept is a recombinant human tumour necrosis factor (TNF), receptor (p75) protein fused with the Fc portion of IgG1 that binds to TNF,. This article reviews the evidence on the efficacy and safety of etanercept in combination with methotrexate, acitretin, narrowband UVB and cyclosporin. The largest body of evidence assesses the combination with methotrexate, although evidence is available for the other combinations. Data suggest that although highly effective as monotherapy, etanercept in combination with a conventional systemic agent can enhance efficacy and allow drug sparing. Potentially, the combination may also result in faster treatment responses and permit safe transitioning from one systemic agent to another. Evidence to date suggests that these benefits can be achieved without significant additional toxicity, although long-term data on the efficacy and safety of the combination in psoriatic populations is limited and further evaluation is warranted. [source]