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Disease Evolution (disease + evolution)
Selected AbstractsNeuropsychiatric movement disorders following streptococcal infectionDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 11 2005K G Walker MB BS The aim of this study was to describe post-streptococcal movement disorders that form part of the acute rheumatic fever complex. The clinical records of patients diagnosed with Sydenham's chorea were analyzed retrospectively to investigate epidemiology, the significance of socioeconomic deprivation, clinical manifestations, treatments, outcomes, long-term morbidity, and disease evolution. Forty-two patients (21 males, 21 females) were diagnosed with Sydenham's chorea. The median presentation age was 9 years 8 months (range 3y 5mo to 13y 2mo). Nineteen patients were of indigenous African ancestry; 23 were of mixed ancestry. All patients lived in poverty and had poor access to medical care. Twelve of the total group had disabling symptoms for longer than 2 years; six of these patients developed paediatric autoimmune neuropsychiatric disorder associated with Streptococcus (Paediatric autoimmune neuropsychiatric disorder associated with Streptococcus [PANDAS]), five Tourette syndrome (TS), and one learning difficulties. Poor outcome was significantly more prevalent in patients of mixed ancestry, in those with a positive family history, previous behavioural problems, or a failure to complete 10 days of penicillin and ,bed-rest'/hospitalization. Sydenham's chorea is one manifestation of post-streptococcal neuropsychiatric movement disorders. This study demonstrates that patients can present with one diagnosis and evolve other neuropsychiatric conditions such as TS and PANDAS. In the South African context, it is important to delineate neuropsychiatric movement disorders associated with streptococcal infections. The potential genetic susceptibility should be explored. [source] Improved detection of chromosomal abnormalities in chronic lymphocytic leukemia by conventional cytogenetics using CpG oligonucleotide and interleukin-2 stimulation: A Belgian multicentric study,GENES, CHROMOSOMES AND CANCER, Issue 10 2009Natalie Put We performed a multicentric study to assess the impact of two different culture procedures on the detection of chromosomal abnormalities in 217 consecutive unselected cases with chronic lymphocytic leukemia (CLL) referred for routine analysis either at the time of diagnosis (n = 172) or during disease evolution (n = 45). Parallel cultures of peripheral blood or bone marrow were set up with the addition of either the conventional B-cell mitogen 12- O -tetradecanoyl-phorbol-13-acetate (TPA) or a combination of CpG oligonucleotide (CpG) and interleukin-2 (IL-2). Cytogenetic analyses were performed on both cultures. Clonal abnormalities were identified in 116 cases (53%). In 78 cases (36%), the aberrant clone was detected in both cultures. Among these, the percentages of aberrant metaphases were similar in both conditions in 17 cases, higher in the CpG/IL-2 culture in 43 cases, and higher in the TPA culture in 18 cases. Clonal aberrations were detected in only one culture, either in CpG/IL-2 or TPA in 33 (15%) and 5 (2%) cases, respectively. Taken together, abnormal karyotypes were observed in 51% with CpG/IL-2 and 38% with TPA (P < 0.0001). Application of FISH (n = 201) allowed the detection of abnormalities not visible by conventional cytogenetic analysis in 80 cases: del(13q) (n = 71), del(11q) (n = 5), +12 (n = 2), del(14q) (n = 1), and del(17p) (n = 1). In conclusion, our results confirm that CpG/IL-2 stimulation increases the detection rate of chromosomal abnormalities in CLL compared with TPA and that further improvement can be obtained by FISH. However, neither conventional cytogenetics nor FISH detected all aberrations, demonstrating the complementary nature of these techniques. © 2009 Wiley-Liss, Inc. [source] Nucleophosmin (NPM1) mutations in adult and childhood acute myeloid leukaemia: towards definition of a new leukaemia entity,HEMATOLOGICAL ONCOLOGY, Issue 4 2009Rachel Rau Abstract Nucleophosmin (NPM) is a ubiquitously expressed chaperone protein that shuttles rapidly between the nucleus and cytoplasm, but predominantly resides in the nucleolus. It plays key roles in ribosome biogenesis, centrosome duplication, genomic stability, cell cycle progression and apoptosis. Somatic mutations in exon 12 of the NPM gene (NPM1) are the most frequent genetic abnormality in adult acute myeloid leukaemia (AML), found in approximately 35% of all cases and up to 60% of patients with normal karyotype (NK) AML. In children, NPM1 mutations are far less frequent, occurring in 8,10% of all AML cases, and in approximately 25% of those with a NK. NPM1 mutations lead to aberrant localization of the NPM protein into the cytoplasm, thus the designation, NPMc+ AML. NPMc+ AML is seen predominantly in patients with a NK and is essentially mutually exclusive of recurrent chromosomal translocations. Patients with NPM1 mutations are twice as likely as those who lack an NPM1 mutation to also have a FMS-like tyrosine kinase (FLT3) internal tandem duplication (ITD) mutation. NPMc+ AML is also characterized by a unique gene expression signature and microRNA signature. NPMc+ AML has important prognostic significance, as NPMc+ AML, in the absence of a coexisting FLT3-ITD mutation, is associated with a favourable outcome. NPM1 mutations have also shown great stability during disease evolution, and therefore represent a possible marker for minimal residual disease detection. Given its distinctive biologic and clinical features and its clear clinical relevance, NPMc+ AML is included as a provisional entity in the 2008 WHO classifications. There is still much to be learned about this genetic alteration, including its exact role in leukaemogenesis, how it interacts with other mutations and why it confers a more favourable prognosis. Further, it represents a potential therapeutic target warranting research aimed at identifying novel small molecules with activity in NPMc+ AML. Copyright © 2009 John Wiley & Sons, Ltd. [source] Familial chronic myeloproliferative disorders: the state of the art,HEMATOLOGICAL ONCOLOGY, Issue 3 2008Elisa Rumi Abstract Familial chronic myeloproliferative disorders are defined when in the same pedigree at least two relatives have a chronic myeloproliferative disorder (CMD) as polycythemia vera (PV), essential thrombocythemia (ET) or primary myelofibrosis (PMF). This condition should be distinguished from inherited disorders with Mendelian transmission and single haematopoietic lineage proliferation, named hereditary erythrocytosis and thrombocytosis. The recently discovered mutations in patients with CMD (V617F and exon 12 of JAK2 gene, MPL gene), and those identified in hereditary erythrocytosis and in hereditary thrombocytosis have improved our ability to discriminate these conditions. In familial CMD, the JAK2 mutations are acquired and occur as secondary genetic events. As both mutations of the JAK2 gene have been reported in the same pedigree, a genetic predisposition to the acquisition of the JAK2 mutations is supposed to be inherited. The prevalence of familial cases within CMD is at least 7.6%. The inheritance pattern of familial CMD is consistent with an autosomal dominant trait with decreased penetrance. The clinical presentation at diagnosis of patients with familial CMD does not differ from that of patients with sporadic CMD. In addition, patients with familial CMD develop the same type of complications (thrombosis and haemorrhage) and disease evolution (post-PV myelofibrosis, post-ET myelofibrosis and leukaemia) observed in patients with sporadic CMD. The 10-year survival is 83% for patients with familial PV, 100% for those with familial ET, and 30% for those with familial PMF. The aim of this review is to focus the state of the art of familial CMD and to offer an overview of inherited conditions causing erythrocytosis and thrombocytosis. Copyright © 2008 John Wiley & Sons, Ltd. [source] Crohn's is not a 6-week disease.INFLAMMATORY BOWEL DISEASES, Issue 8 2004Lifelong management of mild to moderate Crohn's disease Abstract Crohn's disease is an idiopathic, chronic inflammatory disorder of the digestive tract with heterogeneous clinical presentations. Crohn's is currently not a curable disease, and patients are faced with a lifetime of recurrent disease flare-ups and remissions. Management strategies for Crohn's must therefore be targeted toward lifelong management, taking into consideration not only the short-term but also the long-term aspects of the disease. With this in mind, here we review the classifications and natural history of Crohn's disease and discuss possible predictive factors for the disease evolution in a patient. Here we also evaluate the current preferable treatment practices, based on scientifically valid research and collective clinical experience, for the management of mild to moderate Crohn's disease. [source] Resistant pityriasis lichenoides et varioliformis acuta in a 3-year-old boyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2010Successful treatment with methotrexate Pityriasis lichenoides et varioliformis acuta (PLEVA) represents the acute clinical subtype of pityriasis lichenoides (PL) and its occurrence is relatively common during childhood. Diagnosis and treatment may sometimes pose certain difficulties. We present the recalcitrant case of a 3-year-old boy with an asymptomatic polymorphic eruption consisting of multiple, scattered, 0.5 cm, round to ovoid, erythematous papules covered in places with a fine scale, vesicles and superficial erosions with thick hemorrhagic crusts. The correlation of the clinical features with the lesional histopathology favored the diagnosis of PLEVA. No first-line treatment scheme succeeded in controlling the eruption of new lesions. The only therapeutic approach that eventually managed to cease the disease evolution was the combination of prednisolone and methotrexate. [source] Imaging biomarkers in multiple sclerosisJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2010M. Filippi MD Abstract Recent years have witnessed impressive advances in the use of magnetic resonance imaging (MRI) for the assessment of patients with multiple sclerosis (MS). Complementary to the clinical evaluation, conventional MRI provides crucial pieces of information for the diagnosis of MS. However, the correlation between the burden of lesions observed on conventional MRI scans and the clinical manifestations of the disease remains weak. The discrepancy between clinical and conventional MRI findings in MS is explained, at least partially, by the limited ability of conventional MRI to characterize and quantify the heterogeneous features of MS pathology. Other quantitative MR-based techniques, however, have the potential to overcome such a limitation of conventional MRI. Indeed, magnetization transfer MRI, diffusion tensor MRI, proton MR spectroscopy, and functional MRI are contributing to elucidate the mechanisms that underlie injury, repair, and functional adaptation in patients with MS. Such techniques are likely to benefit from the use of high-field MR systems and thus allow in the near future providing additional insight into all these aspects of the disease. This review summarizes how MRI is dramatically changing our understanding of the factors associated with the accumulation of irreversible disability in MS and highlights the reasons why they should be used more extensively in studies of disease evolution and clinical trials. J. Magn. Reson. Imaging 2010;31:770,788. ©2010 Wiley-Liss, Inc. [source] Role of magnetic resonance imaging in the diagnosis and monitoring of multiple sclerosis: Consensus report of the White Matter Study Group,JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 5 2002M. Filippi MD Abstract On June 24,26, 2001, the first meeting of the White Matter Study Group (WMSG) of the International Society for Magnetic Resonance in Medicine (ISMRM) was held in Bordeaux, France. This paper is the report of the consensus reached among the delegates of the meeting on how to use magnetic resonance imaging (MRI) to make an early diagnosis of multiple sclerosis (MS), to measure MS activity accurately and reliably, and to monitor the effect of treatment on disease evolution. J. Magn. Reson. Imaging 2002;15:499,504. Published 2002 Wiley-Liss, Inc. [source] Imaging Spinal Cord Damage in Multiple SclerosisJOURNAL OF NEUROIMAGING, Issue 4 2005M. A. Rocca MD ABSTRACT During the past 2 decades, the considerable improvement of magnetic resonance (MR) technology and the development of new MR strategies capable of providing an in vivo overall assessment of multiple sclerosis (MS) pathology have allowed us to obtain important novel pieces of information on disease evolution in the brain. However, despite this, the correlation between brain MR imaging metrics and clinical disability are still suboptimal. A reason for this discrepancy might be the involvement of clinically eloquent structures, such as the spinal cord, which owing to technical challenges have not been extensively studied using MR imaging until very recently. An objective and accurate estimate of the presence and extent of spinal cord damage might indeed contribute to increasing the strength of the correlations between clinical and MRI metrics. This review summarizes the main results obtained from the application of conventional and modern MR-based techniques for the evaluation of spinal cord damage in MS. [source] Long-term follow-up of 386 consecutive patients with essential thrombocythemia: Safety of cytoreductive therapy,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2009Francesca Palandri Cytotoxic agents like Hydroxyurea, Busulfan and Interferon-alpha are to date the most commonly used therapeutic approaches in Essential Thrombocythemia (ET). However, few data on the efficacy and safety of these agents in the long-term are currently available. We report a retrospective analysis of the long-term outcome of 386 consecutive ET patients, followed at single Institution for a median follow-up of 9.5 years (range, 3,28.5). Cytoreductive therapy was administered to 338 patients (88%), obtaining a response in 86% of cases. Forty-five patients (12%) experienced a thrombosis. Among baseline characteristics, only history of vascular events prior to ET diagnosis predicted a higher incidence of thrombosis. Evolution in acute leukemia/myelofibrosis occurred in 6 (1,5%) and 20 (5%) patients, and was significantly higher in patients receiving sequential cytotoxic agents. Overall survival was 38% at 19 years and was poorer for patients older than 60 years, with higher leukocytes count (>15 × 109/L), hypertension and mellitus diabetes at ET diagnosis and for patients experiencing a thrombotic event during follow-up. Cytoreductive therapy was effective in decreasing platelet number with negligible toxicity; however, thrombocytosis control did not reduce the incidence of thrombosis and, for patients who received sequential therapies, the probability of disease evolution was higher and survival was poorer. Am. J. Hematol. 2009. © 2008 Wiley-Liss, Inc. [source] Management of Descending Necrotizing MediastinitisTHE LARYNGOSCOPE, Issue 4 2004Marc Makeieff MD Abstract Objective/Hypothesis Descending necrotizing mediastinitis is caused by downward spread of neck infections and constitutes a highly lethal complication of oropharyngeal lesions. This infection previously had a much worse prognosis. In recent years, more aggressive management has been recommended. The aim of this study is to evaluate the results with the association of thoracotomy and cervicotomy, medical care in an intensive care unit, and daily washing of drained cervical and thoracic tissues. Study Design Retrospective study of 17 patients treated from 1984 to 1998. Method Descending necrotizing mediastinitis was consecutive to pharyngitis (6 cases), peritonsillar abscess (3 cases), dental abscess (6 cases), foreign body infection (1 case), and laryngitis (1 case). Corticotherapy was reported in seven cases. Twelve patients had no particular medical history. Mean age was 42 years. Mean duration of signs before diagnosis was 6 days. Thoracotomy was associated with the cervical approach in 14 cases, whereas 3 patients were treated by cervicotomy only. Results Fourteen patients of 17 (82.3%) were successfully treated. Three deaths occurred. The mean duration of hospitalization in the intensive care unit was 30 days, and the mean total duration of hospitalization was 45 days. Conclusion Descending necrotizing mediastinitis must be detected as soon as possible by computed tomography (CT) scanning in patients with persistent symptomatologia after treatment for oropharyngeal infections. Prompt surgical drainage with thoracotomy and cervicotomy in all cases of mediastinal involvement below the tracheal carena, use of CT scanning to monitor the disease evolution, and medical management in an intensive care unit significantly reduces the mortality rate to less than 20%. [source] Relationship between atrophy and ,-amyloid deposition in Alzheimer diseaseANNALS OF NEUROLOGY, Issue 3 2010Gaël Chételat PhD Objective Elucidating the role of aggregated ,-amyloid in relation to gray matter atrophy is crucial to the understanding of the pathological mechanisms of Alzheimer disease and for the development of therapeutic trials. The present study aims to assess this relationship. Methods Brain magnetic resonance imaging and [11C]Pittsburgh compound B (PiB)-positron emission tomography scans were obtained from 94 healthy elderly subjects (49 with subjective cognitive impairment), 34 patients with mild cognitive impairment, and 35 patients with Alzheimer disease. The correlations between global and regional neocortical PiB retention and atrophy were analyzed in each clinical group. Results Global and regional atrophy were strongly related to ,-amyloid load in participants with subjective cognitive impairment but not in patients with mild cognitive impairment or Alzheimer disease. Global neocortical ,-amyloid deposition correlated to atrophy in a large brain network including the hippocampus, medial frontal and parietal areas, and lateral temporoparietal cortex, whereas regional ,-amyloid load was related to local atrophy in the areas of highest ,-amyloid load only, that is, medial orbitofrontal and anterior and posterior cingulate/precuneus areas. Interpretation There is a strong relationship between ,-amyloid deposition and atrophy very early in the disease process. As the disease progresses to mild cognitive impairment and Alzheimer disease clinical stages, pathological events other than, and probably downstream from, aggregated ,-amyloid deposition might be responsible for the ongoing atrophic process. These findings suggest that antiamyloid therapy should be administered very early in the disease evolution to minimize synaptic and neuronal loss. ANN NEUROL 2010;67:317,324 [source] Haploinsufficiency and acquired loss of Bcl11b and H2AX induces blast crisis of chronic myelogenous leukemia in a transgenic mouse modelCANCER SCIENCE, Issue 7 2009Akiko Nagamachi Chronic myelogenous leukemia (CML) is a hematological malignancy that begins as indolent chronic phase (CP) but inevitably progresses to fatal blast crisis (BC). p210BCR/ABL, a chimeric protein with enhanced kinase activity, initiates CML CP, and additional genetic alterations account for progression to BC, but the precise mechanisms underlying disease evolution are not fully understood. In the present study, we investigated the possible contribution of dysfunction of Bcl11b, a zinc-finger protein required for thymocyte differentiation, and of H2AX, a histone protein involved in DNA repair, to the transition from CML CP to BC. For this purpose, we crossed CML CP-exhibiting p210BCR/ABL transgenic (BAtg/,) mice with Bcl11b heterozygous (Bcl11b+/,) mice and H2AX heterozygous (H2AX+/,) mice. Interestingly, p210BCR/ABL transgenic, Bcl11b heterozygous (BAtg/,Bcl11b+/,) mice and p210BCR/ABL transgenic, H2AX heterozygous (BAtg/,H2AX+/,) mice frequently developed CML BC with T-cell phenotype and died in a short period. In addition, whereas p210BCR/ABL was expressed in all of the leukemic tissues, the expression of Bcl11b and H2AX was undetectable in several tumors, which was attributed to the loss of the residual normal allele or the lack of mRNA expression. These results indicate that Bcl11b and H2AX function as tumor suppressor and that haploinsufficiency and acquired loss of these gene products cooperate with p210BCR/ABL to develop CML BC. (Cancer Sci 2009; 100: 1219,1226) [source] HLA-DR expression on lymphocyte subsets as a marker of disease activity in patients with systemic lupus erythematosusCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2001J. F. Viallard A major problem in the management of SLE patients is to predict a flare or to distinguish between active and quiescent disease. Serological markers are widely used to assess disease activity, but many patients have close to or normal values for these parameters while exhibiting obvious disease-related signs and symptoms. This study aimed to determine which serological parameters, among ESR, ANA and anti-dsDNA antibody titres, CH50 and the HLA-DR expression on circulating T-lymphocyte subsets, best reflected the development of SLE flares. Sixty SLE patients were included, 34 with quiescent disease throughout the entire follow-up period and 26 who experienced an SLE flare defined as having active disease. According to univariate analysis, all parameters were significantly higher for patients with active disease, with the percentage of CD8+DR+ cells being the most significant parameter (P = 10,7). Multivariate logistic regression analysis identified three independent variables enabling the identification of a lupus flare: CH50, the CD8+DR+ and CD4+DR+ cell percentages among total lymphocytes. The CD8+DR+ cell percentage is the biological parameter most significantly associated with a flare (P < 0·001), even more powerful than CH50 (P < 0·01). HLA-DR expression on CD8+ lymphocytes clearly coincided with disease evolution in seven patients enrolled as having quiescent disease, but who experienced one flare during follow-up that subsequently resolved. The percentage of circulating CD8+DR+ lymphocytes appears to be a biological marker which accurately reflects disease activity. A larger prospective study is needed to demonstrate the real efficacy of this marker in predicting an exacerbation in SLE patients. [source] | ||||||||||||||||||||||