Disease Progression Research Papers - Academia.edu (original) (raw)

A 37-year-old woman presented with photophobia without visual loss associated with chiasmal compression by an unruptured anterior communicating artery (AcomA) aneurysm. She had suffered progressive photophobia for one year. Neuroimaging... more

A 37-year-old woman presented with photophobia without visual loss associated with chiasmal compression by an unruptured anterior communicating artery (AcomA) aneurysm. She had suffered progressive photophobia for one year. Neuroimaging indicated an AcomA aneurysm attached to the chiasm. Photophobia was resolved following clipping of the aneurysm. AcomA aneurysm should be considered in patients who experience photophobia without visual loss.

Malignant eccrine poroma is a rare disease with approximately 200 cases reported in the literature. Regional cutaneous and systemic metastases are rarely observed and their management has been generally unsuccessful. We report on a case... more

Malignant eccrine poroma is a rare disease with approximately 200 cases reported in the literature. Regional cutaneous and systemic metastases are rarely observed and their management has been generally unsuccessful. We report on a case in which topical 5-fluorouracil application and intra-arterial chemotherapy with docetaxel resulted in a histologically confirmed complete response of multiple regional skin metastases for more than 2 years. Despite intravenous administration of docetaxel, slow progression of systemic disease was observed. Ó 2005 British Association of Dermatologists • British Journal of Dermatology 2005 152, pp1051-1055 Locoregional chemotherapy for porocarcinoma, E. de Bree et al. 1053 Ó 2005 British Association of Dermatologists • British Journal of Dermatology 2005 152, pp1051-1055 Locoregional chemotherapy for porocarcinoma, E. de Bree et al. 1055

results of a single neuropsychological test than when it is based on the results of more memory tests. In epidemiological studies and clinical trials the diagnosis of MCI will likely be more stable if impairment on more than one test is... more

results of a single neuropsychological test than when it is based on the results of more memory tests. In epidemiological studies and clinical trials the diagnosis of MCI will likely be more stable if impairment on more than one test is required for amnestic and/or nonamnestic domains.

This is a literature review about large granular lymphocyte leukemia (LGLL), a rare and misdiagnosed oncohematological disease, characterized by a clonal expansion of T-cells (T-LGLL) or NK-cells (NK-LGLL) in the bone marrow and/or... more

This is a literature review about large granular lymphocyte leukemia (LGLL), a rare and misdiagnosed oncohematological disease, characterized by a clonal expansion of T-cells (T-LGLL) or NK-cells (NK-LGLL) in the bone marrow and/or peripheral blood. The clinical features of LGLL include cytopenias (anemia, neutropenia and thrombocytopenia), lymphocytosis (usually discrete), lymphadenopathy, hepatomegaly, splenomegaly, immune abnormalities and constitutional symptoms (fever, night sweats and weight loss). The diagnosis is based on the confirmation of the clonality of T-cells or NK-cells (polymerase chain reaction and Southern blot are the two methods most commonly used) and typical findings of the immunophenotypic analysis of peripheral blood lymphocytes (flow cytometry analyses for specific surface antigens). In contrast to the chronic and indolent course of T-LGLL, NK-LGLL has an acute presentation and poor clinical outcome. There are different current treatment options, depending on clinical presentation.

Pulmonary arterial hypertension is most often diagnosed in its advanced stages because of the nonspecific nature of early symptoms and signs. Although clinical assessment is essential when evaluating patients with suspected pulmonary... more

Pulmonary arterial hypertension is most often diagnosed in its advanced stages because of the nonspecific nature of early symptoms and signs. Although clinical assessment is essential when evaluating patients with suspected pulmonary arterial hypertension, echocardiography is a key screening tool in the diagnostic algorithm. It provides an estimate of pulmonary artery pressure, either at rest or during exercise, and is useful in ruling out secondary causes of pulmonary hypertension. In addition, echocardiography is valuable in assessing prognosis and treatment options, monitoring the efficacy of specific therapeutic interventions, and detecting the preclinical stages of disease. (J Am Soc Echocardiogr 2012;-:---.) High CO can be present in hyperkinetic conditions, such as systemic-to-pulmonary shunts (only in the pulmonary circulation), anemia, hyperthyroidism, and so on.

X-linked adenoleukodystrophy is a genetic disease that affects the degradation of very long-chain fatty acids. In male patients, common pictures are the cerebral form (CALD), myeloneuropathy (AMN), and Addison-only. Objective: To describe... more

X-linked adenoleukodystrophy is a genetic disease that affects the degradation of very long-chain fatty acids. In male patients, common pictures are the cerebral form (CALD), myeloneuropathy (AMN), and Addison-only. Objective: To describe the clinical course of affected male patients from South Brazil between 1993 and 2007. Methods: Affected male patients and their maternal lineages were studied from a clinical, neurological and biochemical standpoint. Results: Eighty-three male patients from 30 families were biochemically evaluated: 51 were affected. 27/51 (54%) presented the cerebral form; 11/51 had AMN (22%); 5 had Addison-only (10%), and 8 (16%) were asymptomatic. Between 2002 and 2006, the minimal incidence was 1:35,000 males in our State (South Brazil). Forty-three affected individuals were followed for 5.4 ± 3.7 years. Of 10 boys detected at early stages, three developed CALD. These three boys and another five CALD at baseline were referred to hematopoietic stem cell transplantation. Seven transplants were carried out, 5 with good clinical evolution after 2.2 years post-transplant. The non-transplanted case was later defined as a stable cerebral form. Discussion: Among the present families, the observed cases were comparable to the 50% expected by Mendelian segregation. Based on the natural history, the number of cases that developed CALD was similar to the expected. Transplants were successful in 70% of cases. The occurrence of a stable cerebral form pointed to an urgent need for better markers of active cerebral disease.

VAZ SALGADO, MA, GARCÍA, CG, LOPEZ MARTIN, JA, GUERRA, E., BENITO, A., SEPULVEDA, JM and CARRATO, A.(2010), Porocarcinoma: Clinical Evolution. Dermatologic Surgery, 36: 264–267. doi: 10.1111/j. 1524-4725.2009. 01412. x

Background: Early detection of white matter lesions in childhood-onset cerebral adrenoleukodystrophy (ALD) is important as hematopoietic cell transplantation (HCT), currently the only effective treatment, is beneficial only if performed... more

Background: Early detection of white matter lesions in childhood-onset cerebral adrenoleukodystrophy (ALD) is important as hematopoietic cell transplantation (HCT), currently the only effective treatment, is beneficial only if performed early in the disease course. Objective: To establish reliable biochemical markers of cerebral disease progression in patients with ALD to aid in treatment planning. Methods: The authors used proton magnetic resonance spectroscopy (MRS) in combination with LCModel analysis to quantify brain metabolites in small volumes (3 to 16 mL) in the occipital and frontal white matter and the splenium of the corpus callosum of 17 unsedated patients and 26 healthy volunteers (adult n ϭ 21, age-matched n ϭ 5) at 4 tesla. Results: Absolute concentrations of 12 metabolites were reliably determined, seven of which were established as markers of lesion development. Among these, creatine and choline containing compounds were the weakest markers while N-acetylaspartate, glutamine, and lipids ϩ lactate were the strongest. The large extent of changes in the markers enabled detection of early neurochemical changes in lesion formation prior to detection of abnormalities by conventional MRI. Concentrations of a number of metabolites were also significantly different between normal appearing white matter of patients and controls indicating biochemical alterations in the absence of cerebral disease. Neurochemical improvements following HCT were measured in six patients. Conclusions: The progression of adrenoleukodystrophy, as well as effectiveness of its treatment, can be assessed with high precision using high field 1 H magnetic resonance spectroscopy in individual patients without the need for sedation. balt4/znl-neurol/znl-neurol/znl00305/znl9349-05a simmsl S‫8؍‬ 12/8/

Young patients with early osteoarthritis (OA) represent a challenging population due to a combination of high functional demands and limited treatment options. Conservative measures such as injection and physical therapy can provide... more

Young patients with early osteoarthritis (OA) represent a challenging population due to a combination of high functional demands and limited treatment options. Conservative measures such as injection and physical therapy can provide short-term pain relief but are only palliative in nature. Joint replacement, a successful procedure in the older population, is controversial in younger patients, who are less satisfied and experience higher failure rates. Therefore, while traditionally not indicated for the treatment of OA, cartilage repair has become a focus of increased interest due to its potential to provide pain relief and alter the progression of degenerative disease, with the hope of delaying or obviating the need for joint replacement. The field of cartilage repair is seeing the rapid development of new technologies that promise greater ease of application, less demanding rehabilitation and better outcomes. Concurrent procedures such as meniscal transplantation and osteotomy, however, remain of crucial importance to provide a normalized biomechanical environment for these new technologies. Level of evidence Systematic review, Level II.

Bruton&a... more

Bruton's tyrosine kinase (BTK) plays a critical role in B cell development and function. We recently described a selective BTK inhibitor, RN486, that blocks B cell receptor (BCR) and Fcγ receptor signaling and is efficacious in animal models of arthritis. The aim of this study was to examine the potential efficacy of BTK in systemic lupus erythematosus (SLE), using an NZB × NZW mouse model of spontaneous SLE. Mice received RN486 or its vehicle (administered in chow) at a final concentration of 30 mg/kg for 8 weeks, starting at 32 weeks of age. The administration of RN486 completely stopped disease progression, as determined by histologic and functional analyses of glomerular nephritis. The efficacy was associated with striking inhibition of B cell activation, as demonstrated by a significant reduction in CD69 expression in response to BCR crosslinking. RN486 markedly reduced the secretion of IgG anti-double-stranded DNA (anti-dsDNA) secretion, as determined by enzyme-linked immunosorbent and enzyme-linked immunospot assays. Flow cytometric analysis demonstrated depletion of CD138(high) B220(low) plasma cells in the spleen. RN486 inhibited secretion of IgG anti-dsDNA but not IgM anti-dsDNA, suggesting that pharmacologic blockade of BTK resembles the reported transgenic expression of low levels of endogenous BTK in B cells. In addition, RN486 may also impact the effector function of autoantibodies, as evidenced by a significant reduction in immune complex-mediated activation of human monocytes in vitro and down-regulation of the expression of macrophage-related and interferon-inducible genes in both the kidneys and spleens of treated mice. Collectively, our data suggest that BTK inhibitors may simultaneously target autoantibody-producing and effector cells in SLE, thus constituting a promising therapeutic alternative for this disease.

Aim: Early-onset schizophrenia (onset before adulthood) is a rare and severe form of the disorder that shows phenotypic and neurobiological continuity with adult-onset schizophrenia. Here, we provide a synthesis of keynote findings in... more

Aim: Early-onset schizophrenia (onset before adulthood) is a rare and severe form of the disorder that shows phenotypic and neurobiological continuity with adult-onset schizophrenia. Here, we provide a synthesis of keynote findings in this enriched population to understand better the neurobiology and pathophysiology of early-onset schizophrenia. Methods: A synthetic and integrative approach is applied to review studies stemming from epidemiology, phenomenology, cognition, genetics and neuroimaging data. We provide conclusions and future directions of research on early-onset schizophrenia. Results: Childhood and adolescentonset schizophrenia is associated with severe clinical course, greater rates of premorbid abnormalities, poor psychosocial functioning and increased severity of brain abnormalities. Early-onset cases show similar neurobiological correlates and phenotypic deficits to adult-onset schizophrenia, but show worse longterm psychopathological outcome. Emerging technological advances have provided important insights into the genomic architecture of earlyonset schizophrenia, suggesting that some genetic variations may occur more frequently and at a higher rate in young-onset than adult-onset cases. Conclusions: Clinical, cognitive, genetic and imaging data suggest increased severity in early-onset schizophrenia. Studying youngeronset cases can provide useful insights into the neurobiological mechanisms of schizophrenia and the complexity of gene-environment interactions leading to the emergence of this debilitating disorder.

METHODS. COMET enrolled 469 ethnically diverse children (ages, 6–11 years) with myopia between –1.25 and –4.50 D. They were randomly assigned to either progressive addition lenses (PALs) with a +2.00 addition (n = 235) or single vision... more

METHODS. COMET enrolled 469 ethnically diverse children (ages, 6–11 years) with myopia between –1.25 and –4.50 D. They were randomly assigned to either progressive addition lenses (PALs) with a +2.00 addition (n = 235) or single vision lenses (SVLs; n = 234), the ...

Creutzfeldt-Jakob disease is a very rare, progressive neurodegenerative disorder that is incurable and always fatal. It is one of the transmissible spongiform encephalopathies caused by prions. Multiple vacuoles in neuropil and neuronal... more

Creutzfeldt-Jakob disease is a very rare, progressive neurodegenerative disorder that is incurable and always fatal. It is one of the transmissible spongiform encephalopathies caused by prions. Multiple vacuoles in neuropil and neuronal loss in the gray matter gives the classical sponge-like appearance of brain and are responsible for the typical clinical symptoms. In this report, we present 4 cases referred to the neurology department of Uludağ University with neurological symptoms. Patients were evaluated with electroencephalogram and magnetic resonance imaging, and performed brain biopsies for further investigation. For definitive diagnosis of Creutzfeldt-Jakob disease, accumulation of prion protein in brain was detected immunohistochemically. Patients died within weeks in consequence of rapid progression of the disease. Although Creutzfeldt-Jakob disease is an infrequent disorder, when a patient presents with characteristic clinical symptoms such as rapidly progressive dementia with myoclonus, the diagnosis of Creutzfeldt-Jakob disease should be taken into consideration.

This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the... more

This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.

Biological research increasingly relies on network models to study complex phenomena. Signal Transduction Pathways are molecular circuits that model how cells receive, process, and respond to information from the environment providing... more

Biological research increasingly relies on network models to study complex phenomena. Signal Transduction Pathways are molecular circuits that model how cells receive, process, and respond to information from the environment providing snapshots of the overall cell dynamics. Most of the attempts to reconstruct signal transduction pathways are limited to single regulator networks including only genes/proteins. However, networks involving a single type of regulator and neglecting transcriptional and post-transcriptional regulations mediated by transcription factors and microRNAs, respectively, may not fully reveal the complex regulatory mechanisms of a cell. We observed a lack of computational instruments supporting explorative analysis on this type of three-component signal transduction pathways. We have developed CyTRANSFINDER, a new Cytoscape plugin able to infer three-component signal transduction pathways based on user defined regulatory patterns and including miRNAs, TFs and gene...

Thyroid hemiagenesis (TH) is a rare inborn anomaly, resulting from failure of one thyroid lobe development. It is usually detected incidentally during investigation of concomitant thyroid disorders. The reported patient first presented... more

Thyroid hemiagenesis (TH) is a rare inborn anomaly, resulting from failure of one thyroid lobe development. It is usually detected incidentally during investigation of concomitant thyroid disorders. The reported patient first presented hypothyroidism at the age of 49, when Hashimoto's thyroiditis (HT) and left thyroid lobe agenesis was diagnosed. L-thyroxine (LT4) replacement therapy restored hormonal balance. Two years later, the patient developed features of Graves' hyperthyroidism. The antithyroid pharmacotherapy by thiamazole was used. However, due to severe side-effects it was discontinued, and radioiodine treatment was applied. Four months after 131I administration, symptoms of hypothyroidism appeared, so thyroid hormone substitution was reintroduced. The patient, whose observation period has now reached 5 years, under LT4 replacement therapy, remains both clinically and biochemically euthyroid. The described case displays a very rare coincidence of hypothyroidism due to HT converted into Graves' hyperthyroidism, accompanying TH. Each of these three entities, may influence the thyroid function in a different way, hence, systematic follow-up and individual therapeutic management is required.

Renal anemia is the result of chronic kidney disease (CKD) and deteriorates with disease progression. Anemia may be the first sign of kidney disease. In all patients with anemia and CKD, diagnostic evaluation is required. Prior to... more

Renal anemia is the result of chronic kidney disease (CKD) and deteriorates with disease progression. Anemia may be the first sign of kidney disease. In all patients with anemia and CKD, diagnostic evaluation is required. Prior to diagnosing renal anemia, it is necessary to eliminate the other possible causes. Direct correlation between the concentration of hemoglobin and the stage of renal failure is well known. Early development of anemia is common in diabetic patients. Correction of anemia may slow the progression of CKD. Anemia is an independent risk factor for developing cardiovascular disease in patients with CKD. Treatment of anemia in patients with CKD is based on current guidelines. Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group has produced comprehensive clinical practice guidelines for the management of anemia in CKD patients and ERBP (European Renal Best Practice) group its position statement and comments on the KDIGO guidelines. The Croatian Socie...

Exosomes are small vesicles comprised of a lipid bilayer containing various proteins, RNAs and bioactive lipids. They act as intercellular messengers that give the ability to communicate between both cells of the same type and other cell... more

Exosomes are small vesicles comprised of a lipid bilayer containing various proteins, RNAs and bioactive lipids. They act as intercellular messengers that give the ability to communicate between both cells of the same type and other cell types. They are released by healthy cells, both constitutively and upon cell activation and play an important role in immune system function. Exosomes are essential for healthy physiological conditions, however under pathological circumstances, they act to potentiate cellular stress and damage. This review explores the characteristics, biogenesis, role(s) in the pathogenesis of diseases and role(s) in progression of cancer of these nano-sized messages-in-a-vesicle: exosomes.

An to nio Giulivi 1 • Mo ham mad Afzal 1 2 De part ment of Epi de mi ol o gy and Com mu ni ty Med i cine, The Uni ver si ty of Ot tawa, Ot tawa, Can a da • 3 Sta tis tics and Risk As sess ment Sec tion, Blood Safe ty Sur veil lance and... more

An to nio Giulivi 1 • Mo ham mad Afzal 1 2 De part ment of Epi de mi ol o gy and Com mu ni ty Med i cine, The Uni ver si ty of Ot tawa, Ot tawa, Can a da • 3 Sta tis tics and Risk As sess ment Sec tion, Blood Safe ty Sur veil lance and Health Care Ac quired In fec tions Di vi sion, Cen tre for In fec tious Dis ease Pre ven tion and Con trol, Pub lic Health Agen cy of Can a da, Ot tawa, ONT, Can a da Eco nom ic bur den of hep a ti tis C in Can a da and the po ten tial im pact of pre ven tion Re sults from a dis ease mod el

Objective.To report baseline and followup data on the first 438 patients with systemic sclerosis (SSc) included in the Belgian Systemic Sclerosis Cohort.Methods.According to LeRoy and Medsger’s classification, 73 patients with limited SSc... more

Objective.To report baseline and followup data on the first 438 patients with systemic sclerosis (SSc) included in the Belgian Systemic Sclerosis Cohort.Methods.According to LeRoy and Medsger’s classification, 73 patients with limited SSc (lSSc), 279 with limited cutaneous SSc (lcSSc), and 86 with diffuse cutaneous SSc (dcSSc) were included. History was collected and clinical examination, blood tests, and paraclinical investigations were repeated. The Disease Activity Score (DAS) and Disease Severity Score (DSS) of several organ systems were computed. An organ system was considered to demonstrate SSc if the corresponding DSS was ≥ 1.Results.At baseline, patients with dcSSc had more general, joint/tendon, muscle, gastrointestinal, and kidney involvement. Mean DLCO was below normal in patients with lSSc, indicating unsuspected lung involvement. Patients with anti-Scl-70 had more vascular, skin, joint/tendon, and lung involvement. Patients with anti-RNA polymerase III had more skin and...

Background. In the United Kingdom, diabetic nephropathy is a leading cause of end-stage renal disease. There is a higher incidence amongst subjects of Indo-Asian and African-Caribbean origin compared with Caucasians that is not wholly... more

Background. In the United Kingdom, diabetic nephropathy is a leading cause of end-stage renal disease. There is a higher incidence amongst subjects of Indo-Asian and African-Caribbean origin compared with Caucasians that is not wholly explained by the differences in the prevalence of diabetes. Therefore, we postulated that this observation could be related to variations in the rate of progression of renal disease according to racial origin. Methods. We conducted a retrospective case-note review of 1684 adult attendees of the diabetes clinic. Forty-®ve patients were found with renal impairment (serum creatinine P170 mmolul) due to diabetic nephropathy. The patients were of Indo-Asian (ns10), African-Caribbean (ns11), and Caucasian (ns24) origin. Progression of nephropathy was assessed by analysing (i) the doubling of serum creatinine through construction of Kaplan±Meier curves and (ii) the slope (b) of the rate of change in serum creatinine using linear regression analysis in relation to demographic variables, putative risk factors for nephropathy and antihypertensive drug therapy. Results. There were no statistically signi®cant differences between systolic and diastolic blood pressure, glycaemic control, smoking habit, baseline proteinuria, and usage of angiotensin-converting enzyme inhibitors between the three groups. The proportion of patients doubling their creatinine was signi®cantly higher in the Indo-Asian compared with the African-Caribbean and Caucasian groups (100, 45 and 50%; Ps0.025 respectively). In addition, the mean (95% CI) of b (mmolulumonth) was highest in the Indo-Asian (5.36 (2.21±8.52)) compared with the African-Caribbean (3.14 (0.82±5.46)) and Caucasian (2.22 (1.31±3.14)) groups (Ps0.035). The mean ranks of b were highest in the Indo-Asian group (Ps0.038) after adjusting for marginal differences in blood pressure age, gender, baseline proteinuria, anti-hypertensive treatment, and smoking habit. Conclusions. In this small cohort of type 2 diabetic subjects with established renal disease, the rate of decline in renal function is accelerated in Indo-Asian subjects. This observation could be related to differences in renoprotection from antihypertensive therapy.

Vitiligo is an acquired depigmentary skin disorder due to the loss of cutaneous melanocytes or alteration in melanocyte function, affecting over 0.5% of the world population. The exact cause of melanocyte loss in non-segmental vitiligo is... more

Vitiligo is an acquired depigmentary skin disorder due to the loss of cutaneous melanocytes or alteration in melanocyte function, affecting over 0.5% of the world population. The exact cause of melanocyte loss in non-segmental vitiligo is still debatable, but many observations have pointed to the main role of cellular immunity. Earlier evidence has shown that depigmenting vitiligo skin is accompanied by CD8+ T cytotoxic lymphocytes infiltrates at the dermal-epidermal junction. Dysregulation of Tregs may be one of the factors that can break tolerance to melanocyte self-antigens and contribute to the pathogenesis of vitiligo. The objectives of the present study were to provide evidence of the presence of a functional defect and decrease of peripheral regulatory T cells in patients affected by vitiligo, supporting the hypothesis of their involvement in the pathogenesis of the disease, opening new possibilities to advance therapeutic approaches.

Retinal vascular diseases such as diabetic retinopathy and retinopathy of prematurity are major causes of visual loss. Although the focus of a great deal of research has been on the aetiology of vascular growth, it is now emerging that... more

Retinal vascular diseases such as diabetic retinopathy and retinopathy of prematurity are major causes of visual loss. Although the focus of a great deal of research has been on the aetiology of vascular growth, it is now emerging that anomalies in other retinal cell types, especially glial cells, occur very early in the course of the disease. Glial cells have major roles in every stage of disease, from the earliest subtle variations in neural function, to the development of epi-retinal membranes and tractional detachment. Therefore, having a firm understanding of the function of retinal glia is important in our understanding of retinal disease and is crucial for the development of new treatment strategies.

Background: Several prognostic models have been developed to stage hepatocellular carcinoma (HCC) but there is no general consensus on which is the most reliable. We compared three prognostic indices (Okuda, CLIP, and BCLC scoring... more

Background: Several prognostic models have been developed to stage hepatocellular carcinoma (HCC) but there is no general consensus on which is the most reliable. We compared three prognostic indices (Okuda, CLIP, and BCLC scoring systems) in a large series of cirrhotic patients with HCC undergoing nonsurgical treatment in terms of their ability to classify patients into different risk groups Methods: We retrospectively studied 268 Italian patients with HCC. A total of 146 patients were treated with ablation, 132 with percutaneous ethanol injection, and 14 with radiofrequency ablation; 103 underwent transcatheter arterial chemoembolisation and 19 had supportive care alone. Factors determining survival were analysed by univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard regression models. Okuda, CLIP, and BCLC scores evaluated before treatment were applied. Results: Median survival was 25.7 months. In a multivariate analysis, portal vein thrombosis, a fetoprotein, total bilirubin, and tumour size were significant predictors of survival. Okuda, CLIP, and BCLC scores were all able to predict survival (p,0.001). They identified two, four, and six risk groups, respectively, with a median survival ranging from 27 to 19 months for Okuda, 30 to 5 months for CLIP, and 43 to 7 months for BCLC. Conclusions: Both CLIP and BCLC scores were more effective than the Okuda score in stratifying patients into different risk groups with early-intermediate HCC. However, the BCLC scoring system gave a better prediction of prognosis in patients with disease diagnosis at a very early stage.

A large variation in prognosis is observed despite the use of clinical prognostic factors in patients with advanced non-small cell lung cancer (NSCLC). It is likely that this variation is due to the different biological properties of the... more

A large variation in prognosis is observed despite the use of clinical prognostic factors in patients with advanced non-small cell lung cancer (NSCLC). It is likely that this variation is due to the different biological properties of the tumour cells. In this work we aimed to identify gene signature that could predict survival in advanced NSCLC. Total RNA was extracted from five 5 μm-thick sections of the FFPE using the High Pure RNA Paraffin Kit (Roche). RNA amplification was performed using WT-Ovation™ FFPE RNA Amplification System V2 (NuGen). The amplified cDNA was then labelled and hybridised onto Illumina HumanRef-8 v3.0 Expression BeadChips. Microarray data analysis was subsequently performed using Genespring GX version 9.0. Out of 75 FFPE samples, only 32 had sufficient RNA quality and quantity for microarray gene expression analysis. Patients were grouped into long and short survival groups based on the time to cancer-related death. After normalization and filtration, 19,002 genes were selected for differential gene expression analysis. A total of 440 genes differed significantly between the long and short survival groups (ANOVA, p <; 0.05, with Benjamini and Hochberg False Discovery Rate multiple testing correction). Unsupervised Hierarchial Clustering with Pearson correlation and average linkage identified two broad clusters of patients corresponding to the long and short survival. Thirteen genes were selected based on the TTest, 2-fold expression changes, principal components analysis and univariate Cox regression analysis and risk scores were calculated for each patient. These gene signatures were independent predictors of survival. The model was validated with a published microarray data from 130 patients with NSCLC. Using Gene Set Analysis (GSA), we found certain biological processes including metastasis and chemotherapy resistance were up-regulated in the short survival group while TID pathway and MAPKKK cascade were enriched in th- - e long survival group. As the conclusion, there is several distinct gene expression profiles associated with survival of patients with advanced stage NSCLC. Survival outcomes in advanced NSCLC could be predicted based on a 13-gene signature.

We review data from our institution demonstrating the benefits of cardiac rehabilitation and exercise training on coronary risk factors, exercise capacity, behavioral characteristics, and quality of life in various subgroups of patients.... more

We review data from our institution demonstrating the benefits of cardiac rehabilitation and exercise training on coronary risk factors, exercise capacity, behavioral characteristics, and quality of life in various subgroups of patients. In addition, we discuss our research in several other areas of preventive cardiology, including lipid disorders, hypertension, left ventricular hypertrophy, fish oils, and antioxidants. We believe that we are now in a very exciting era in which a multifactorial approach to the primary and secondary prevention of coronary artery disease is needed in order to further reduce morbidity and mortality rates.

Objective: To assess cognition in major depressed (MD), Alzheimer's disease (AD), and depression in AD elderly. Method: Subjects were evaluated by Mini Mental, Rey Auditory Verbal Learning Test, Rey Complex Figure, Digit Span,... more

Objective: To assess cognition in major depressed (MD), Alzheimer's disease (AD), and depression in AD elderly. Method: Subjects were evaluated by Mini Mental, Rey Auditory Verbal Learning Test, Rey Complex Figure, Digit Span, Similarities, Trail Making A/B, Verbal Fluency and Stroop. One-way ANOVA and multivariate models were used to compare the performance of each group on neuropsychological tests. Results: We evaluated 212 subjects. Compared to MD, attention, working memory, processing speed and recall showed significantly better in controls. Controls showed significantly higher performance in all cognitive measures, except in attention compared to AD. Verbal fluency, memory, processing speed and abstract reasoning in MD was significantly higher compared to AD. AD was significantly better in general cognitive state than depression in AD. All other cognitive domains were similar. Conclusion: A decreasing gradient in cognition appeared from the control to depression in AD, with MD and AD in an intermediate position.

To check the reliability of the commonly used neurological scoring systems taking the nerve conduction studies as the reference. Diagnosed diabetics (n=60) were selected by purposive sampi ng Detection and grading of neuropathy were done... more

To check the reliability of the commonly used neurological scoring systems taking the nerve conduction studies as the reference. Diagnosed diabetics (n=60) were selected by purposive sampi ng Detection and grading of neuropathy were done according to Diabetic Neuropathy Symptom Score (DrNS), modified Neuropathy Symptom Score (NSS), Diabetic Neuropathy Examination (DNE) and modified Neuropathy Disability Score (NDS). For the nerve conduction studies, amplitudes, velocities and latencies of minimum two (Sural, Peroneal) and maximum six, i.e., three sensory (Sural, Ulnar, Median) and three motor (Peroneal, Ulnar, Tibial) nerves were checked. If the patient had 2 or more than two abnormal findings in any of the nerve he was labeled to have peripheral sensorimotor neuropathy. Later the sensitivity, specificity and diagnostic efficacy of each neurological score was checked taking nerve conduction studies as the gold standard. Taking the NCS as gold standard DNS, DNE, NSS and NDS had 64.1%...

We report a family with autosomal dominant centronuclear (myotubular) myopathy caused by a novel mutation, p.A618D, in dynamin 2 (DNM2). The 64-year-old mother and 26-year-old daughter had neonatal onset with hypotonia and weak suckling,... more

We report a family with autosomal dominant centronuclear (myotubular) myopathy caused by a novel mutation, p.A618D, in dynamin 2 (DNM2). The 64-year-old mother and 26-year-old daughter had neonatal onset with hypotonia and weak suckling, followed by improvement, then slowly progressive muscle weakness and respiratory restriction. Muscle biopsy showed radial sarcoplasmic strands around the frequent central nuclei. Electrophysiology revealed predominantly myopathic patterns without peripheral nerve involvement. Centronuclear myopathy with neonatal onset caused by a DNM2 mutation in the C-terminal part of the pleckstrin homology domain may have a favorable prognosis and follow a course similar to adult-onset centronuclear myopathy. We advise respiratory follow-up in these patients.

Our aim was to investigate the existence of an association between B cell responsiveness to hepatitis C virus (HCV) core protein and progression of liver disease. In fact, the persistence of HCV infection is permitted by avoidance of... more

Our aim was to investigate the existence of an association between B cell responsiveness to hepatitis C virus (HCV) core protein and progression of liver disease. In fact, the persistence of HCV infection is permitted by avoidance of viral clearance, despite chronic inflammation in the liver; this process ends with the development of hepatocellular carcinoma in many patients. On the basis of computerized prediction of antigenicity of the genomic sequence of HCV core protein, three 15-mer peptides (named Q15V, R15P, and G15V) were synthesized to be used as antigens in an enzyme immunoassay. Sera from 97 patients (65 males and 32 females) were tested: 43 patients had mild chronic liver disease (steatofibrosis, chronic persistent, or chronic active hepatitis) and 54 had cirrhosis, which was complicated by hepatocellular carcinoma (HCC) in 19. Seventy-six patients were positive to anti-HCV testing by second generation ELISA and 21 were negative. Rates of positivity for synthetic peptide...

Cost and effectiveness are usually modeled according to one studied event or one health state with parametric or non-parametric methods. In this paper, we propose an original method for assessing total costs while incorporating the... more

Cost and effectiveness are usually modeled according to one studied event or one health state with parametric or non-parametric methods. In this paper, we propose an original method for assessing total costs while incorporating the dynamics of change in the health status of patients. A semi-Markov model in which the distributions of sojourn times are explicitly defined is developed. The hazard function of sojourn times is modeled by Weibull distributions specific to each transition. A vector of covariates is incorporated into the hazard function of each transition. From a regression model for costs, a cumulative cost function is derived. An estimation of the mean cost per patient in each state defined in the semi-Markov model could thus be made, and this enables us to identify the determinants of direct costs. The results of incremental net benefit (INB) are assessed using the bootstrap method. A cost-effectiveness analysis is performed in order to compare two strategies of follow-up in the colorectal cancer study. Two hundred and forty patients were enrolled in this study. Three health states are defined for patients with curative resection of colorectal cancer: alive without relapse, alive with relapse, and dead. The mean survival is 4.35 and 4.12 years, respectively, in the standard and moderate follow-up groups. We show that mean cost differs significantly by follow-up strategy and Dukes stage. Finally, the INB is assessed and this indicates that neither of the strategies compared was more cost-effective than the other.

Multiple sclerosis (MS) patients frequently develop some form of ocular motor dysfunction during the disease. In previous studies, ocular motor abnormalities were found to correlate with clinical disability and with impaired cognitive... more

Multiple sclerosis (MS) patients frequently develop some form of ocular motor dysfunction during the disease. In previous studies, ocular motor abnormalities were found to correlate with clinical disability and with impaired cognitive performance. The objective of this study was to assess the pursuit ocular movement (POM) frequency in relapsing-remitting (RR) and secondary progressive (SP) MS patients by using a vision-based nonintrusive eye tracker. POM frequency was significantly lower (p \ 0.001) in MS patients compared to normal controls. No differences between RR and SP-MS patients and no correlation between POM and expanded disability status scale (EDSS) score were found. This exploratory study suggests that our vision-based system is a new simple non-intrusive method showing impairment of POM values in MS patients, even in the absence of association with clinical disability (EDSS). Future works on larger cohorts of MS patients might validate this eye tracking in MS clinical practice.

To compare the EULAR and SDAI50 response measures (RMs) and their impact on future response to treatment in patients with early rheumatoid arthritis (ERA). Biologic naïve ERA patients from the Canadian early ArThritis CoHort (CATCH) with... more

To compare the EULAR and SDAI50 response measures (RMs) and their impact on future response to treatment in patients with early rheumatoid arthritis (ERA). Biologic naïve ERA patients from the Canadian early ArThritis CoHort (CATCH) with complete data at baseline, 3 and 6 months were evaluated. Kappa statistics were used to evaluate the agreement between the EULAR (moderate or good response) and SDAI50 RMs. The RMs at 3 months were also compared for their ability to predict low disease activity state (LDAS) or remission (REM) at 6 months. A total of 1124 patients were evaluated. Of those, 215 (30%) and 294 (45%) patients failed to achieve a EULAR and SDAI50 RMs respectively. There was a good agreement between EULAR and SDAI50 RMs with a Kappa of 0.59 (95% CI 0.53- 0.66). Throughout the range of disease activity, the SDAI50 response was shown to be more stringent than the EULAR response. Multivariable linear regression analysis demonstrated that both RMs at 3 months were associated w...

In the Western world, calcified aortic valve stenosis is the most common form of valvular heart disease, affecting up to 3% of adults over the age of 75 years. It is a gradually progressive disease, characterized by a long asymptomatic... more

In the Western world, calcified aortic valve stenosis is the most common form of valvular heart disease, affecting up to 3% of adults over the age of 75 years. It is a gradually progressive disease, characterized by a long asymptomatic phase that may last for several decades, followed by a short symptomatic phase associated with severe restriction of the valve orifice. Investigations on treatments for aortic valve stenosis are still in progress. Thus, it is believed that calcification of aortic valve stenosis is similar to the process of atherosclerosis that occurs in coronary artery disease. Recent studies have suggested that cholesterol lowering through the use of statins may have a salutary effect on the progression of aortic valve stenosis

The progressive myoclonic epilepsies are a rare group of debilitating epileptic encephalopathies characterized by myoclonic seizures, progressive neurological dysfunction and dementia. In the past year advances in gene mapping have... more

The progressive myoclonic epilepsies are a rare group of debilitating epileptic encephalopathies characterized by myoclonic seizures, progressive neurological dysfunction and dementia. In the past year advances in gene mapping have isolated gene loci for the majority of progressive myoclonic disorders, paving the way for specific diagnosis, more accurate prognosis and risk calculation, as well as opening the potential for prenatal and pre-symptomatic diagnosis in at risk families.

There is accumulating evidence that the metabolism of several trace elements is altered in diabetes mellitus and that these nutrients might have specific roles in the pathogenesis and progress of this disease. The aim of present study was... more

There is accumulating evidence that the metabolism of several trace elements is altered in diabetes mellitus and that these nutrients might have specific roles in the pathogenesis and progress of this disease. The aim of present study was to compare the level of essential ...

Limited information on salvage treatment in patients affected by pancreatic cancer is available. At failure, about half of the patients present good performance status (PS) and are candidate for further treatment. Patients >18 years,... more

Limited information on salvage treatment in patients affected by pancreatic cancer is available. At failure, about half of the patients present good performance status (PS) and are candidate for further treatment. Patients >18 years, PS ⩾50, with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-containing chemotherapy, and progression-free survival (PFS) 2 toxicity was: neutropenia in five patients (12%), thrombocytopenia, liver and vomiting in three (7%), fatigue in two (5%). In total, 10 patients (24%) yielded a partial response, 11 a stable disease. Progression-free survival at 6 months was 14.6%. Median survival was 5.2 months. Survival was significantly longer in patients with previous PFS >6 months and in patients without pancreatic localisation. A clinically relevant improvement of quality of life was observed in numerous domains. Raltitrexed–oxaliplatin regimen may constitute a treatment opportunity in gemcitabine-resistant metastatic pancreatic...

To examine the frequency and timing of progression from type 2 to type 1 retinopathy of prematurity (ROP) in the Early Treatment for Retinopathy of Prematurity Study. Methods: Infants with prethreshold ROP that was no worse than low risk... more

To examine the frequency and timing of progression from type 2 to type 1 retinopathy of prematurity (ROP) in the Early Treatment for Retinopathy of Prematurity Study. Methods: Infants with prethreshold ROP that was no worse than low risk in 1 or both eyes, based on the RM-ROP2 model, were examined every 2 to 4 days for at least 2 weeks. Using the Early Treatment for Retinopathy of Prematurity Study-defined classification of eyes as having type 1 or type 2 prethreshold ROP, we analyzed the time to conversion from type 2 to type 1. Data were analyzed for 1 randomly selected eye for each child. Results: Of 294 eyes at first diagnosis of type 2 ROP, 65 (22.1%) progressed to type 1 (mean [SD] interval, 9.0 [6.6] days; median, 7.0 days). Of 217 eyes with type 2 ROP that had an examination in less than 7 days, 25 Author Affiliations are listed at the end of this article. Group Information: A list of the Early Treatment for Retinopathy of Prematurity Cooperative Group members was published in

The propeptides PICP and PINP are derived from the synthesis of type I collagen, a major matrix protein of bone and soft tissues. The aim of this cross-sectional study was to investigate their value as indicators of the aggressivity of... more

The propeptides PICP and PINP are derived from the synthesis of type I collagen, a major matrix protein of bone and soft tissues. The aim of this cross-sectional study was to investigate their value as indicators of the aggressivity of breast cancer. Serum PINP, PICP, and total alkaline phosphatase were determined from 89 breast cancer patients. Forty had major bone and/or soft tissue metastases with an aggressive disease course: the progressive disease (PD) group. Forty-nine had either none or minor bone and/or soft tissue metastases with a stable clinical course: the stable disease group (SD). The mean value of PINP in the PD group was 7.2 times higher than that in the SD group (276 +/- 79 microg/l versus 38 +/- 3 microg/l, respectively; P = 0.005), whereas PICP mean value was only 1.7 times higher in the PD group (174 +/- 20 microg/l versus 100 +/- 5 microg/l; P = 0.001). The ratio of PICP to PINP was 1.02 +/- 0.07 in the PD group and 3.07 +/- 0.18 in the SD group (P < 0.001)....

Antibodies against nucleosomes are a serological hallmark of systemic lupus erythematosus (SLE). Apoptotic cells are the unique source of nucleosomes, which are formed through cleavage of chromatin by nucleases. These nucleosomes and... more

Antibodies against nucleosomes are a serological hallmark of systemic lupus erythematosus (SLE). Apoptotic cells are the unique source of nucleosomes, which are formed through cleavage of chromatin by nucleases. These nucleosomes and other autoantigens targeted in SLE are expressed in apoptotic blebs or at the surface of apoptotic cells. Therefore, it is conceivable that circulating antibodies can influence apoptotic cell clearance. Using an in vitro phagocytosis assay, we analysed the phagocytic efficacy for apoptotic cells of resident peritoneal macrophages from pre-morbid and diseased lupus mice. The assay was carried out in the presence of autologous serum, using autologous apoptotic thymocytes as targets. Under these conditions macrophages from diseased MRL/lpr and NZB NZW(F1) lupus mice, and from age-matched NZB mice showed a decreased phagocytic efficacy (decrease 47%, 48% and 37%, respectively compared to measurements in pre-morbid mice). The cause of this decrease resides in the serum, and is not due to an acquired defect of macrophages. In conclusion, during disease progression in murine SLE, apoptotic cell clearance becomes impaired, which might amplify further disease progression.

BACKGROUNDAberrant DNA methylation, which results in leukemogenesis, is frequent in patients with myelodysplastic syndromes (MDS) and is a potential target for pharmacologic therapy. Decitabine indirectly depletes methylcytosine and... more

BACKGROUNDAberrant DNA methylation, which results in leukemogenesis, is frequent in patients with myelodysplastic syndromes (MDS) and is a potential target for pharmacologic therapy. Decitabine indirectly depletes methylcytosine and causes hypomethylation of target gene promoters.Aberrant DNA methylation, which results in leukemogenesis, is frequent in patients with myelodysplastic syndromes (MDS) and is a potential target for pharmacologic therapy. Decitabine indirectly depletes methylcytosine and causes hypomethylation of target gene promoters.METHODSA total of 170 patients with MDS were randomized to receive either decitabine at a dose of 15 mg/m2 given intravenously over 3 hours every 8 hours for 3 days (at a dose of 135 mg/m2 per course) and repeated every 6 weeks, or best supportive care. Response was assessed using the International Working Group criteria and required that response criteria be met for at least 8 weeks.A total of 170 patients with MDS were randomized to receive either decitabine at a dose of 15 mg/m2 given intravenously over 3 hours every 8 hours for 3 days (at a dose of 135 mg/m2 per course) and repeated every 6 weeks, or best supportive care. Response was assessed using the International Working Group criteria and required that response criteria be met for at least 8 weeks.RESULTSPatients who were treated with decitabine achieved a significantly higher overall response rate (17%), including 9% complete responses, compared with supportive care (0%) (P < .001). An additional 12 patients who were treated with decitabine (13%) achieved hematologic improvement. Responses were durable (median, 10.3 mos) and were associated with transfusion independence. Patients treated with decitabine had a trend toward a longer median time to acute myelogenous leukemia (AML) progression or death compared with patients who received supportive care alone (all patients, 12.1 mos vs. 7.8 mos [P = 0.16]; those with International Prognostic Scoring System intermediate-2/high-risk disease, 12.0 mos vs. 6.8 mos [P = 0.03]; those with de novo disease, 12.6 mos vs. 9.4 mos [P = 0.04]; and treatment-naive patients, 12.3 mos vs. 7.3 mos [P = 0.08]).Patients who were treated with decitabine achieved a significantly higher overall response rate (17%), including 9% complete responses, compared with supportive care (0%) (P < .001). An additional 12 patients who were treated with decitabine (13%) achieved hematologic improvement. Responses were durable (median, 10.3 mos) and were associated with transfusion independence. Patients treated with decitabine had a trend toward a longer median time to acute myelogenous leukemia (AML) progression or death compared with patients who received supportive care alone (all patients, 12.1 mos vs. 7.8 mos [P = 0.16]; those with International Prognostic Scoring System intermediate-2/high-risk disease, 12.0 mos vs. 6.8 mos [P = 0.03]; those with de novo disease, 12.6 mos vs. 9.4 mos [P = 0.04]; and treatment-naive patients, 12.3 mos vs. 7.3 mos [P = 0.08]).CONCLUSIONSDecitabine was found to be clinically effective in the treatment of patients with MDS, provided durable responses, and improved time to AML transformation or death. The duration of decitabine therapy may improve these results further. Cancer 2006. © 2006 American Cancer Society.Decitabine was found to be clinically effective in the treatment of patients with MDS, provided durable responses, and improved time to AML transformation or death. The duration of decitabine therapy may improve these results further. Cancer 2006. © 2006 American Cancer Society.

Objectives – During the last years, the association between apolipoprotein E (APOE) polymorphism and disease severity in multiple sclerosis (MS) has been studied with conflicting results. As a result of a considerable individual... more

Objectives – During the last years, the association between apolipoprotein E (APOE) polymorphism and disease severity in multiple sclerosis (MS) has been studied with conflicting results. As a result of a considerable individual variation in the clinical course of MS, there is no consensus method for measuring progression using single assessments of disability. Recently, Multiple Sclerosis Severity Score (MSSS) method has been proposed for comparing disease progression using single data. We evaluate in our population if there is any correlation between APOE genotype and severity according to MSSS.Methods – We studied 82 patients followed up in our Neurology Unit throughout the year 2005, diagnosed with MS, and with disease duration of at least 2 years. We collected data concerning demographic and clinical variables including age of onset, disease duration, Expanded Disability Status Scale (EDSS) score and the total number of relapses. When reached, we determined the latency to EDSS scores of 4.0 and 6.0. We calculated progression index (PI) and relapse rate (RR). We ascertained MSSS for our patients in the global MSSS table.Results – We found four patients heterozygous for the E2 allele and 16 for the E4 allele. No patient was homozygous for E2 or E4. RR (P = 0.017 with 95% CI: 0.005–0.57) and PI (P = 0.016 with 95% CI: 0.004–0.38) were significantly lower in E4 carriers. MSSS scores were not associated with carriership of E2 or E4.Conclusion – Our results show no effect of the APOE genotype on the severity of MS measured by MSSS, as a recently published meta-analysis has noticed. So, our data do not support a role for APOE in MS severity, in spite of the seeming influence shown using other measures such as PI. MSSS is probably the best method to measure severity with a single measure of disability and should be used more frequently when performing genetic research.