Significant Disease (significant + disease)

Distribution by Scientific Domains


Selected Abstracts


The value of EZH2, p27kip1, BMI-1 and MIB-1 on biopsy specimens with low-risk prostate cancer in selecting men with significant prostate cancer at prostatectomy

BJU INTERNATIONAL, Issue 2 2010
Tineke Wolters
OBJECTIVE To assess the additional prognostic value of the molecular markers EZH2, MIB-1, p27kip1 and BMI-1 on needle biopsies from men with low-risk prostate cancer, as this disease in needle biopsies shows a heterogeneous clinical outcome, and while it is known that the expression of these tissue markers is predictive of the clinical outcome after radical prostatectomy (RP) their value in prostate biopsies is largely unknown. PATIENTS AND METHODS The study included men participating in a screening study, diagnosed with low-risk prostate cancer and subsequently treated with RP. Immunohistochemical staining for EZH2, MIB-1, p27kip1 and BMI-1 on the needle biopsies were (semi)quantitatively scored and expression levels were related to significant disease at RP. Clinical low-risk prostate cancer was defined as a prostate-specific antigen (PSA) level of ,10 ng/mL, clinical T-stage ,2, biopsy Gleason score ,6, a PSA density of <0.20 ng/mL/g and two or fewer positive cores. Significant PC at RP was defined as presence of any of extracapsular extension, Gleason pattern 4/5, or tumour volume ,0.5 mL. RESULTS In all, 86 biopsy specimens were included; there was high EZH2 expression (>1.0%) in 42% and a low p27kip expression (<90%) in 63%. Significant disease was present in 44 (51%) RP specimens. A high EZH2 (odds ratio 3.19, P = 0.043) and a low p27kip1 (4.69, P = 0.036) were independent predictors for significant prostate cancer at RP. CONCLUSIONS The determination of EZH2 and p27kip1 on diagnostic needle biopsies supports the selection of men with indolent prostate cancer at RP. Especially p27kip1 could improve the pretreatment risk assessment of patients with low-risk prostate cancer. [source]


Antibody bound to the surface antigen MPB83 of Mycobacterium bovis enhances survival against high dose and low dose challenge

FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2004
Mark A. Chambers
Abstract Tuberculosis caused by infection with Mycobacterium tuberculosis or Mycobacterium bovis is a significant disease of man and animals. Whilst cellular immunity is the major immunological component required for protection against these organisms, recent reports have suggested that monoclonal antibodies can modify infection with M. tuberculosis. To test whether the same was true for M. bovis infection, we determined the effect of preincubation of M. bovis with a monoclonal antibody on subsequent intravenous infection of mice. Antibodies bound to the surface of M. bovis increased the survival time of mice infected with M. bovis and changed the morphology of granulomas and the distribution of acid-fast bacilli in the lung. These studies suggest that antibodies directed to the surface of virulent mycobacteria can modulate their virulence in vivo. [source]


Gill disease of marine fish caused by infection with Neoparamoeba pemaquidensis

JOURNAL OF FISH DISEASES, Issue 9 2001
B L Munday
Amoebic gill disease (AGD) of maricultured salmonids, turbot, Scophthalmus maximus (L.), European seabass, Dicentrarchus labrax (L.), and sharpsnout seabream, Diplodus puntazzo (Cetti), caused by Neoparamoeba pemaquidensis has been reported from Australia (Tasmania), Ireland, France, Chile, North America (Washington State and California) and Spain. Of the salmonids, Atlantic salmon, Salmo salar L., appears to be the most susceptible with rainbow trout, Oncorhynchus mykiss (Walbaum), also suffering significant disease. Only minor outbreaks have been reported in coho, O. kisutch (Walbaum), and chinook salmon, O. tshawytscha (Walbaum). The disease now accounts for 10,20% of production costs of Atlantic salmon in Tasmania and has lead to temporary abandonment of culture of this species in parts of Spain. It is of lesser, but still significant, importance in other countries. Much is known about the pathology of AGD but the pathophysiology of the disease is poorly understood. There is evidence that non-specific immunity is involved in fish acquiring resistance to AGD, but no unequivocal evidence exists for protection as a result of specific immune responses. To date, for salmonids, the only effective treatment for AGD is a freshwater bath. Control procedures based on modification of management strategies have been minimal and virtually unresearched. [source]


Appropriateness of therapy for fistulizing Crohn's disease: findings from a national inflammatory bowel disease cohort

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010
V. Pittet
Aliment Pharmacol Ther 2010; 32: 1007,1016 Summary Background, About 30,50% of patients with Crohn's disease (CD) develop fistulae, implying significant disease burden and complicated clinical management. Aim, To assess appropriate use of therapy for fistulizing CD patients enrolled in the Swiss Inflammatory Bowel Disease Cohort using criteria developed by the European Panel on the Appropriateness of Crohn's disease Therapy. Methods, Specific questionnaires were used to gather information on disease and its management. We assessed appropriateness of therapy at enrolment for adult CD patients with one or several fistulae. Results, Two hundred and eighty-eight CD patients had fistulizing disease, of which 80% had complex fistulae and 32% currently had active draining fistulae. Mean age (s.d.) at diagnosis was 27 years (11), 51% males. Of the patients, 78% were judged as having globally an appropriate therapy, which was more often given for complex fistulae (87%) than for simple fistulae (67%). Antibiotics, azathioprine/MP, methotrexate and conservative surgery were almost always appropriate. Anti-tumor necrosis factor , was considered globally appropriate (91%), although most often with an uncertain indication. The 5ASA compounds, steroids and aggressive surgery were most often inappropriate (84%, 58% and 86% respectively). Conclusions, Formal appropriateness criteria for CD therapy were applied to a national cohort of IBD patients. For more than three-quarters of the patients with fistulizing CD, therapy was globally appropriate. [source]


Vascular bed-specific thrombosis

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2007
W. C. AIRD
Summary., Hemostasis represents a finely tuned balance between procoagulant and anticoagulant forces. An imbalance of these forces may lead to clinically significant disease, including arterial, venous and/or microvascular thrombosis. The vast majority of hypercoagulable states are associated with local thrombus formation. The goal of this review is to discuss the mechanisms underlying site-specific thrombosis. [source]


Evidence for differential host preference in Microdochium nivale var. majus and Microdochiumnivale var. nivale

PLANT PATHOLOGY, Issue 2 2000
D.R. Simpson
The pathogenicity of Microdochium nivale var. majus and var. nivale was tested on wheat, rye and oat seedlings using both visual disease scoring and quantitative PCR measurements. In an individual inoculation trial at 10°C var. majus and var. nivale were strongly pathogenic towards wheat and rye, with var. nivale causing slightly greater disease in rye. At this temperature only var. nivale caused significant disease of oats. In a further experiment M. nivale was inoculated as a series of mixtures of the two varieties and incubated at 15°C. The ratio of the varieties present in the inoculum and present at harvest was analysed by quantitative PCR and this enabled a coefficient of selection to be calculated for the varieties on each host. M. nivale var. majus showed a weak selective advantage over var. nivale on wheat (0.33 ± 0.08) and oat seedlings (0.35 ± 0.016) and M. nivale var. nivale showed a strong selective advantage over var. majus on rye seedlings (0.92 ± 0.26). The isolates were also compared for sensitivity to benzoxazolinone (BOA), a hydroxamic acid compound derived from rye leaves. M. nivale var majus was found to be significantly more sensitive to BOA than M. nivale var. nivale, indicating a possible mechanism for the selective advantage of var. nivale growing on rye. This is the first substantiated indication of a significant difference in host preference between Microdochium nivale var. majus and var. nivale. [source]


Long-Term Follow-Up for Children Treated With Surgical Intervention for Chronic Rhinosinusitis

THE LARYNGOSCOPE, Issue 12 2006
Rodney P. Lusk MD
Abstract Objectives/Hypothesis: The goal of this study is to retrospectively compare the long-term, 10 year, outcomes of surgical versus medical management of young children with chronic rhinosinusitis. Study Design: This is a retrospective, age-matched, cohort outcome study performed at a tertiary-care hospital. Methods: Two groups of young children (2,5 yr old) with chronic rhinosinusitis were treated with endoscopic sinus surgery or medically managed and evaluated 10 years after their initial therapy. Of the 131 eligible patients, 67 could be located and consented to participate in the study. Six symptoms (day cough, night cough, irritability or crankiness, headaches, nasal airway obstruction, and purulent rhinorrhea) were used to assess the outcome of their treatment. Results: Children undergoing endoscopic sinus surgery had more significant disease as noted on the computed tomography (CT) scans. Their symptom severity, however, was similar. When individual symptoms were compared, there were no statistically significant differences between the surgically and medically managed groups. When the mean was controlled for baseline symptom severity and CT severity, there was statistical improvement in nasal airway obstruction and decreased rhinorrhea. There was a trend toward improvement in cough, but this was not statistically significant. Parenteral assessment of improvement (change) in symptoms (P = .001) and their degree of satisfaction with treatment (P = .005) was significantly higher in the surgically managed group. Conclusions: Children who have chronic rhinosinusitis improve in their symptoms of nasal airway obstruction and purulent discharge if they undergo surgery. Parents of young children with chronic rhinosinusitis appear to be more satisfied with the outcome of surgical management than medical management when assessed 10 years later. [source]


Tumor characteristics in screening for prostate cancer with and without rectal examination as an initial screening test at low PSA (0.0,3.9 ng/ml)

THE PROSTATE, Issue 4 2001
André N. Vis
Abstract BACKGROUND The value of rectal examination as initial screening test for prostate cancer at low PSA values (0.0,3.9 ng/ml) was determined by evaluating the number and tumor characteristics of the cancers detected. METHODS Two study populations were subjected to screening with (n,=,10,226) and without (n,=,10,753) rectal examination as initial screening test. The number of cancers detected at low PSA values for both screening regimens, the corresponding biopsy and radical prostatectomy tumor characteristics were assessed. Possibly harmless cancers were defined as small (<,0.5,ml) organ-confined tumors without Gleason growth-patterns 4/5. RESULTS At low PSA, 26.6% (117/440) of screen-detected cancers were detected after the evaluation of a suspicious rectal examination. The number of cancers and tumor aggressiveness features were highly associated with serum-PSA level. The proportion of possibly harmless disease steadily declined from 100% (PSA 0.0,0.9 ng/ml) to 15.4% (PSA 3.0,3.9 ng/ml). Rectal examinations were performed unnecessarily in 94.7,100% of cases, when detection of clinically significant disease was aimed at. Using PSA (and a cut-off of 3.0 ng/ml) as the only screening tool, 24.3% (121/498) of screen-detected cancers were in the PSA range 3.0,3.9 ng/ml, and 60.0% were assessed as clinically significant. CONCLUSIONS Rectal examination as initial screening test for prostate cancer at low PSA values may be replaced by screening using serum-PSA only. At PSA levels below 3.0 ng/ml, 289 rectal examinations are required to find one case of clinically significant disease, and 96 rectal examinations are needed to diagnose prostate cancer of any size, grade, or stage. Prostate 47:252,261, 2001. © 2001 Wiley-Liss, Inc. [source]


A novel non-invasive tool for disease surveillance of free-ranging whales and its relevance to conservation programs

ANIMAL CONSERVATION, Issue 2 2010
K. Acevedo-Whitehouse
Abstract The numbers of potentially pathogenic microorganisms that have been isolated from stranded cetaceans in the last three decades underscore the urgent need for methods of detection of microorganisms that might cause significant disease and increase the likelihood of population declines. We have designed and implemented two non-invasive techniques for the collection of exhaled breath condensate (blow) from free-ranging whales and demonstrated their suitability for the detection of respiratory bacteria. We successfully collected 22 individual blow samples from eight cetacean species. Using well-established molecular techniques we detected three bacterial genera (Haemophilus, Streptococcus and Staphylococcus). Haemophilus spp. was detected in fin whale Balaenoptera physalus, sperm whale Physeter macrocephalus, humpback whale Megaptera novaeangliae and gray whale Eschrichtius robustus blows, while unidentified , -hemolytic streptococci and Staphylococcus aureus were detected in gray whale and blue whale Balaenoptera musculus blows. The detection limit of the test was determined as 1 CFU mL,1. None of the identified bacteria were found in environmental (control) samples, suggesting that their presence in the blows was genuine and not due to inadvertent contamination. While the population-level relevance of these bacteria is as yet unclear and it is possible that they are commensal microorganisms, S. aureus has been identified previously as a high-risk pathogen to cetacean health, and streptococci have increasingly been associated with cetacean mortality events. We suggest that future cetacean monitoring programs of vulnerable or threatened species include blow sampling as a means to determine the prevalence of the respiratory bacteria in the populations and monitor spatiotemporal fluctuations as indicators of changes in cetacean health. [source]


One-year Outcomes Following Coronary Computerized Tomographic Angiography for Evaluation of Emergency Department Patients with Potential Acute Coronary Syndrome

ACADEMIC EMERGENCY MEDICINE, Issue 8 2009
Judd E. Hollander MD
Abstract Objectives:, Coronary computerized tomographic angiography (CTA) has high correlation with cardiac catheterization and has been shown to be safe and cost-effective when used for rapid evaluation of low-risk chest pain patients from the emergency department (ED). The long-term outcome of patients discharged from the ED with negative coronary CTA has not been well studied. Methods:, The authors prospectively evaluated consecutive low- to intermediate-risk patients who received coronary CTA in the ED for evaluation of a potential acute coronary syndrome (ACS). Patients with cocaine use, known cancer, and significant comorbidity reducing life expectancy and those found to have significant disease (stenosis , 50% or ejection fraction < 30%) were excluded. Demographics, medical and cardiac history, labs, and electrocardiogram (ECG) results were collected. Patients were followed by telephone contact and record review for 1 year. The main outcome was 1-year cardiovascular death or nonfatal acute myocardial infarction (AMI). Results:, Of 588 patients who received coronary CTA in the ED, 481 met study criteria. They had a mean (±SD) age of 46.1 (±8.8) years, 63% were black or African American, and 60% were female. There were 53 patients (11%) rehospitalized and 51 patients (11%) who received further diagnostic testing (stress or catheterization) over the subsequent year. There was one death (0.2%; 95% confidence interval [CI] = 0.01% to 1.15%) with unclear etiology, no AMI (0%; 95% CI = 0 to 0.76%), and no revascularization procedures (0%; 95% CI = 0 to 0.76%) during this time period. Conclusions:, Low- to intermediate-risk patients with a Thrombosis In Myocardial Infarction (TIMI) score of 0 to 2 who present to the ED with potential ACS and have a negative coronary CTA have a very low likelihood of cardiovascular events over the ensuing year. [source]


The value of EZH2, p27kip1, BMI-1 and MIB-1 on biopsy specimens with low-risk prostate cancer in selecting men with significant prostate cancer at prostatectomy

BJU INTERNATIONAL, Issue 2 2010
Tineke Wolters
OBJECTIVE To assess the additional prognostic value of the molecular markers EZH2, MIB-1, p27kip1 and BMI-1 on needle biopsies from men with low-risk prostate cancer, as this disease in needle biopsies shows a heterogeneous clinical outcome, and while it is known that the expression of these tissue markers is predictive of the clinical outcome after radical prostatectomy (RP) their value in prostate biopsies is largely unknown. PATIENTS AND METHODS The study included men participating in a screening study, diagnosed with low-risk prostate cancer and subsequently treated with RP. Immunohistochemical staining for EZH2, MIB-1, p27kip1 and BMI-1 on the needle biopsies were (semi)quantitatively scored and expression levels were related to significant disease at RP. Clinical low-risk prostate cancer was defined as a prostate-specific antigen (PSA) level of ,10 ng/mL, clinical T-stage ,2, biopsy Gleason score ,6, a PSA density of <0.20 ng/mL/g and two or fewer positive cores. Significant PC at RP was defined as presence of any of extracapsular extension, Gleason pattern 4/5, or tumour volume ,0.5 mL. RESULTS In all, 86 biopsy specimens were included; there was high EZH2 expression (>1.0%) in 42% and a low p27kip expression (<90%) in 63%. Significant disease was present in 44 (51%) RP specimens. A high EZH2 (odds ratio 3.19, P = 0.043) and a low p27kip1 (4.69, P = 0.036) were independent predictors for significant prostate cancer at RP. CONCLUSIONS The determination of EZH2 and p27kip1 on diagnostic needle biopsies supports the selection of men with indolent prostate cancer at RP. Especially p27kip1 could improve the pretreatment risk assessment of patients with low-risk prostate cancer. [source]


The origin of human pathogens: evaluating the role of agriculture and domestic animals in the evolution of human disease

BIOLOGICAL REVIEWS, Issue 3 2006
Jessica M. C. Pearce-Duvet
ABSTRACT Many significant diseases of human civilization are thought to have arisen concurrently with the advent of agriculture in human society. It has been hypothesised that the food produced by farming increased population sizes to allow the maintenance of virulent pathogens, i.e. civilization pathogens, while domestic animals provided sources of disease to humans. To determine the relationship between pathogens in humans and domestic animals, I examined phylogenetic data for several human pathogens that are commonly evolutionarily linked to domestic animals: measles, pertussis, smallpox, tuberculosis, taenid worms, and falciparal malaria. The majority are civilization pathogens, although I have included others whose evolutionary origins have traditionally been ascribed to domestic animals. The strongest evidence for a domestic-animal origin exists for measles and pertussis, although the data do not exclude a non-domestic origin. As for the other pathogens, the evidence currently available makes it difficult to determine if the domestic-origin hypothesis is supported or refuted; in fact, intriguing data for tuberculosis and taenid worms suggests that transmission may occur as easily from humans to domestic animals. These findings do not abrogate the importance of agriculture in disease transmission; rather, if anything, they suggest an alternative, more complex series of effects than previously elucidated. Rather than domestication, the broader force for human pathogen evolution could be ecological change, namely anthropogenic modification of the environment. This is supported by evidence that many current emerging infectious diseases are associated with human modification of the environment. Agriculture may have changed the transmission ecology of pre-existing human pathogens, increased the success of pre-existing pathogen vectors, resulted in novel interactions between humans and wildlife, and, through the domestication of animals, provided a stable conduit for human infection by wildlife diseases. [source]