Home About us Contact
|
Home About us Contact | ||
|
|
||
Disease Entity (disease + entity)
Kinds of Disease Entity Selected AbstractsTrigeminal Trophic Syndrome,Report of Four Cases and Review of the LiteratureDERMATOLOGIC SURGERY, Issue 5 2004Parrish Sadeghi MD Background. Trigeminal trophic syndrome is a unilateral, frequently crescent-shaped neurotrophic ulceration of the face occurring after injury to the trigeminal nerve. The appearance of the ulcers resembles other disease entities such as granulomatous disease, neoplasm, vasculitis, infection, and factitial dermatitis. Objectives. The objectives of this study are to increase awareness of this disorder and to emphasize the importance of eliciting a thorough neurologic history when evaluating facial ulcerations. Methods. Four cases are reported and, using MEDLINE, the English and non-English literature from 1982 to 2002 is reviewed. Results. Including this report, there have been 60 cases of trigeminal trophic syndrome reported from 1982 to 2002. The age at presentation ranged from 14 months to 93 years. Time of onset from injury to the trigeminal ganglion or its branches and the development of the ulcers ranged from 2 weeks to 30 years. One-third of the patients had undergone trigeminal nerve ablation for the treatment of trigeminal neuralgia and another third had a history of stroke. Other causes included craniotomy, head trauma, herpes infection. Conclusion. The majority of cases of trigeminal trophic syndrome are associated with a history of stroke or trigeminal nerve ablation. Successful surgical outcome can be achieved if the underlying neurologic pathology is addressed before the reconstructive procedure. [source] The role of Lay Review Committees in diabetes researchDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2003David P. Stenger Abstract Type 1 diabetes is unique among disease entities in having a large voluntary health nonprofit organization (the Juvenile Diabetes Research Foundation) that employs the process of review by laypersons (following a review by scientists) in selecting the recipients of its funding awards to individual investigators/trainees: grants, career-development awards, fellowships, and ,innovative grants.' Therefore, that organization can be a suitable model on which an examination of lay review can be based. This paper summarizes (1) the history of how lay review originated and (2) this foundation's experience with it, (3) assesses the impact of the procedure on the discipline of diabetes science, and (4) examines the role it might play in the future, given the current state of that discipline. Copyright © 2003 John Wiley & Sons, Ltd. [source] Clinical Value of the Tissue Doppler S Wave to Characterize Left Ventricular Hypertrophy as Defined by EchocardiographyECHOCARDIOGRAPHY, Issue 4 2010Demian Chejtman M.D. Left ventricular hypertrophy (LVH) may be a physiological finding and may also be associated with different disease entities and hence, with different outcomes. Regional myocardial function can be assessed with color Doppler tissue imaging, specifically by the waveform of the isovolumic contraction (IC) period and the regional systolic wave ("s"). Methods and Results: We studied five groups (G): healthy, sedentary young volunteers (G1, n:10); healthy sedentary adult volunteers (G2, n:8); and subjects with LVH (left ventricular mass index >125 g/m2) including: high performance athletes (G3, n:21), subjects with hypertension (G4, n:21), subjects with hypertrophic cardiomyopathy (HCM) (G5, n:18). We measured peak "s" wave velocity (cm/sec) at the basal and mid septum, the IC/s ratio, and basal to mid-septal velocity difference (BMVD) of the "s" wave. Regional "s" wave values (cm/sec) were G1 = 5.6 ± 1; G2 = 5.4 ± 0.8; G3 = 5.7 ± 0.6; G4 = 5.3 ± 1.1; G5 = 4.2 ± 1.1 (P < 0.0001). The IC/s ratio was G1 = 0.28 ± 0.18; G2 = 0.39 ± 0.21; G3 = 0.23 ± 0.10; G4 = 0.42 ± 0.15; G5 = 0.64 ± 0.15 (P < 0.0001). The BMVD (cm/sec) was G1 = 2 ± 0.51; G2 = 1.71 ± 0.29; G3 = 1.78 ± 0.44; G4 = 1.26 ± 0.96; G5 = 0.45 ± 0.4 (P < 0.0001). IC/s < 0.38 discriminated physiological from pathological forms of hypertrophy (sensitivity 90%; specificity 88%). Peak "s" wave velocity discriminated HCM from other causes of hypertrophy, with a cutoff value of 4.46 cm/sec (sensitivity 72%; specificity 90%). BMVD <0.98 cm/sec detected HCM with 89% sensitivity and 86% specificity. Conclusions: Peak "s" wave velocity and two indices: IC/s and BMDV are novel parameters that may allow to discriminate physiological from pathological forms of hypertrophy as well as different subtypes of hypertrophy. (ECHOCARDIOGRAPHY 2010;27:370-377) [source] Pathology of peripheral intrahepatic cholangiocarcinoma with reference to tumorigenesisHEPATOLOGY RESEARCH, Issue 4 2008Yasuni Nakanuma Cholangiocarcinomas (CCs) are neoplasms with cholangiocyte differentiation, and may arise from cholangiocytes of the biliary tree and possibly cholangiocyte progenitor cells. Intrahepatic CCs can be divided into the perihilar and peripheral types. Peripheral CCs present grossly as a mass forming tumor, and histologically as an adenocarcinoma of varying shapes and phenotypes. Some peripheral CCs (ductular type) are characterized by: (i) a histological resemblance to reactive bile ductules; (ii) the expression of neural cell adhesion molecule (NCAM) and vimentin. This type shows: (i) grossly, a blurred border; and (ii) histologically, carcinoma cells replacing the adjoining hepatocytes at the border of the tumor. It is frequently associated with neutrophilic infiltration and also with granulocyte and granulocyte macrophage colony-stimulating factors. We propose to call this type "ductular CC." The other peripheral CC (duct type) includes ordinary adenocarcinoma with well to moderately differentiated tubular and micropapillary patterns and is negative for NCAM but positive for mucin. This type can be called "duct CC," and shows a rather compressive growth. Interestingly, CC components of combined hepatocellular CC share the features of ductular CC, suggesting that hepatic progenitor cells may be involved in the tumorigenesis of ductular CC. The biological behavior of ductular CC and duct CC remains obscure, and follow-up and molecular studies on these tumors are required in order for these two CCs to be recognized as disease entities, and so as to evaluate their carcinogenesis. [source] Human disease resulting from gene mutations that interfere with appropriate nuclear factor-,B activationIMMUNOLOGICAL REVIEWS, Issue 1 2005Jordan S. Orange Summary:, The nuclear factor (NF)-,B family of transcription factors serves vital roles in a wide array of cell functions. An increasing number of human genetic lesions that result in defined disease entities are linked to inappropriate activation of NF-,B. The resulting aberrant NF-,B function can lead to cellular defects that ultimately impair normal developmental processes, host immune defenses, or both. Molecular defects that lie upstream in cell-signaling pathways and rely upon NF-,B activation tend to give a more specific phenotype, whereas those closer to the actual NF-,B proteins have broader defects. A detailed study of these diseases can provide insight into the biochemistry of NF-,B activation as well as the role of NF-,B in human health. [source] Imbalance of plasma membrane ion leak and pump relationship as a new aetiological basis of certain disease statesJOURNAL OF INTERNAL MEDICINE, Issue 6 2003G. Ronquist Abstract. The basis for life is the ability of the cell to maintain ion gradients across biological membranes. Such gradients are created by specific membrane-bound ion pumps [adenosine triphosphatases (ATPases)]. According to physicochemical rules passive forces equilibrate (dissipate) ion gradients. The cholesterol/phospholipid ratio of the membrane and the degree of saturation of phospholipid fatty acids are important factors for membrane molecular order and herewith a determinant of the degree of non-specific membrane leakiness. Other operative principles, i.e. specific ion channels can be opened and closed according to mechanisms that are specific to the cell. Certain compounds called ionophores can be integrated in the plasma membrane and permit specific inorganic ions to pass. Irrespective of which mechanism ions leak across the plasma membrane the homeostasis may be kept by increasing ion pumping (ATPase activity) in an attempt to restore the physiological ion gradient. The energy source for this work seems to be glycolytically derived ATP formation. Thus an increase in ion pumping is reflected by increased ATP hydrolysis and rate of glycolysis. This can be measured as an accumulation of breakdown products of ATP and end-products of anaerobic glycolysis (lactate). In certain disease entities, the balance between ATP formation and ion pumping may be disordered resulting in a decrease in inter alia (i.a.) cellular energy charge, and an increase in lactate formation and catabolites of adenylates. Cardiac syndrome X is proposed to be due to an excessive leakage of potassium ions, leading to electrocardiographic (ECG) changes, abnormal Tl-scintigraphy of the heart and anginal pain (induced by adenosine). Cocksackie B3 infections, a common agent in myocarditis might also induce an ionophore-like effect. Moreover, Alzheimer's disease is characterized by the formation of extracellular amyloid deposits in the brain of patients. Perturbation of cellular membranes by the amyloid peptide during the development of Alzheimer's disease is one of several mechanisms proposed to account for the toxicity of this peptide on neuronal membranes. We have studied the effects of the peptide and fragments thereof on 45Ca2+ -uptake in human erythrocytes and the energetic consequences. Treatment of erythrocytes with the ,1,40 peptide, results in qualitatively similar nucleotide pattern and decrease of energy charge as the treatment with Ca2+ -ionophore A23187. Finally, in recent studies we have revealed and published in this journal that a rare condition, Tarui's disease or glycogenosis type VII, primarily associated with a defect M-subunit of phosphofructokinase, demonstrates as a cophenomenon an increased leak of Ca2+ into erythrocytes. [source] Hypotonic duodenograms of postbulbar duodenal lesions: Pictorial essayJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 3 2000Yukiharu Sumi SUMMARY General features are described and examples are provided of the radiological manifestations of postbulbar duodenal lesions, particularly the findings on hypotonic duodenograms. Hypotonic duodenography does not always reveal the characteristic findings of postbulbar duodenal lesions, but it helps to evaluate luminal stenosis and diagnose disease entities even in lesions that show non-specific findings. Radiologists should be familiar with the radiological findings of postbulbar duodenal lesions and know which kinds of lesions can affect the postbulbar duodenum. This is important in making a differential diagnosis and in preventing delays in diagnosis. [source] Classification and management of chronic sialadenitis of the parotid glandJOURNAL OF ORAL REHABILITATION, Issue 1 2009S. WANG Summary, Saliva has numerous oral functions and multiple functions in relation to digestion in the upper gastrointestinal tract. Chronic salivary hypofunction can lead to severe adverse health outcomes. Chronic sialadenitis is one of the major conditions that can cause salivary hypofunction. A correct diagnosis and management of chronic sialadenitis is essential for the recovery of salivary hypofunction. Chronic sialadenitis of the parotid gland is often seen in the clinic, sometimes also referred to as recurrent pyogenic parotitis, recurrent parotitis, non-obstructive parotitis, sialadenitis or obstructive parotitis, among other terms. The literature describes several different classifications and denominations for chronic sialadenitis of the parotid gland. These various classifications and denominations complicate the definition and diagnostic criteria, and if chronic sialadenitis of the parotid gland can develop into Sjogren's syndrome remains unclear. Treatment of this condition is also a challenging problem. Here, we review the presented classification and denomination of chronic sialadenitis of the parotid gland, proposing a classification based on the disease entities identified in a long-term follow-up investigation, and discuss the treatment principles for the condition. [source] Sarcoidosis of the skin , A dermatological puzzle: important differential diagnostic aspects and guidelines for clinical and histopathological recognitionJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2010G Tchernev Abstract Sarcoidosis of the skin may have an extremely heterogeneous clinical presentation, so that the definitions of ,great imitator' and ,clinical chameleon' have long been used. There is, in fact, a large group of skin diseases that can enter the differential diagnosis with cutaneous sarcoid manifestations, either clinically or/and pathologically. As the clinical consequences and the prognosis of these groups of diseases are often very different, it is important to correctly plan the diagnostic workup. The diagnostic process in this case often presents a challenge as no single test is sufficiently specific, so that a certain diagnosis can be only made in the presence of a compatible clinical and radiographic picture, along with histopathological evidence of non-necrotizing, epithelioid cell granulomas, and exclusion of other potential aetiologies. For practical reasons, four main groups of skin conditions capable of mimicking sarcoidosis can be identified: (i) transmissible, infectious diseases; (ii) allergic and immunological manifestations of various aetiologies; (iii) granulomatous diseases of various aetiologies; and (iv) lymphomas and pseudolymphomas. The aim of this article is to describe the main clinical and histopathological findings of such disease entities, and to discuss the role of those features (morphological, pathological and laboratory) that can help distinguish them from sarcoidosis of the skin. [source] Pyloric gland metaplasia and pouchitis in patients with ileal pouch-anal anastomosesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010R. KARIV Aliment Pharmacol Ther,31, 862,873 Summary Background, Diagnosis and management of chronic antibiotic-refractory pouchitis and Crohn's disease of the pouch can be challenging. Pyloric gland metaplasia is a histological feature indicative of chronic mucosal inflammation. Its value in diagnosis and prognosis of pouch disorders has not been investigated. Aim, To assess the prevalence, diagnostic and prognostic value, and risk factors of pyloric gland metaplasia in pouch patients. Methods, Patients were identified from our prospectively maintained Pouchitis Database. Pouch biopsy specimens were re-reviewed for pyloric gland metaplasia and other histological features. Two cohorts of patients were studied: a historical cohort (n = 111) and the second, a validation cohort (n = 100). Univariate and multivariate analyses were performed to assess risk factors for pyloric gland metaplasia. Results, The prevalence of pyloric gland metaplasia in the historical cohort and validation cohort was 45 (40.1%) and 24 (24.0%), respectively. The sensitivity and specificity of pyloric gland metaplasia for the diagnosis of chronic antibiotic-refractory pouchitis or Crohn's disease were 70.7% and 92.5%, respectively, for the first cohort and 39.0% and 86.4%, respectively, for the 2nd validation cohort. In multivariate analysis of the first cohort, patients with refractory pouchitis or Crohn's disease were 28 times (95% CI, 7.3,107.1) more likely to have pyloric gland metaplasia than those with a normal pouch or irritable pouch syndrome. The factor of refractory pouchitis or Crohn's disease remained in the model for the 2nd validation cohort with odds ratio of 4.58 (95% CI, 1.6,13.4). Conclusions, Pyloric gland metaplasia is associated with diagnosis of chronic antibiotic-refractory pouchitis or Crohn's disease of the pouch and appears to be a specific marker for both disease entities. [source] Review article: current status of liver transplantation in HIV-infected patientsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2004G. W. Neff Summary The increases in survival of patients infected with human immunodeficiency virus is attributed to the introduction of combination human immunodeficiency virus antiviral therapy, better known as highly active anti-retroviral therapy. In fact, survival statistics have improved such that individuals often succumb to other disease entities, notably liver failure and not from acquired immunodeficiency syndrome complications. Liver transplantation has been introduction in this patient population in several centres around the world. This review will discuss the current clinical status of liver transplantation in individuals suffering from human immunodeficiency virus infection. [source] Overlap between neurodegenerative disordersNEUROPATHOLOGY, Issue 2 2005Richard A. Armstrong Neurodegenerative disorders are characterized by the formation of distinct pathological changes in the brain, including extracellular protein deposits, cellular inclusions, and changes in cell morphology. Since the earliest published descriptions of these disorders, diagnosis has been based on clinicopathological features, namely, the coexistence of a specific clinical profile together with the presence or absence of particular types of lesion. In addition, the molecular profile of lesions has become an increasingly important feature both in the diagnosis of existing disorders and in the description of new disease entities. Recent studies, however, have reported considerable overlap between the clinicopathological features of many disorders leading to difficulties in the diagnosis of individual cases and to calls for a new classification of neurodegenerative disease. This article discusses: (i) the nature and degree of the overlap between different neurodegenerative disorders and includes a discussion of Alzheimer's disease, dementia with Lewy bodies, the fronto-temporal dementias, and prion disease; (ii) the factors that contribute to disease overlap, including historical factors, the presence of disease heterogeneity, age-related changes, the problem of apolipoprotein genotype, and the co-occurrence of common diseases; and (iii) whether the current nosological status of disorders should be reconsidered. [source] Genetic pathways to glioblastomasNEUROPATHOLOGY, Issue 1 2005Hiroko Ohgaki Glioblastomas, the most frequent and malignant human brain tumors, may develop de novo (primary glioblastoma) or by progression from low-grade or anaplastic astrocytoma (secondary glioblastoma). These glioblastoma subtypes constitute distinct disease entities that affect patients of different ages and develop through different genetic pathways. Our recent population-based study in the Canton of Zürich, Switzerland, shows that primary glioblastomas develop in older patients (mean age, 62 years) and typically show LOH on chromosome 10q (69%) and other genetic alterations (EGFR amplification, TP53 mutations, p16INK4a deletion, and PTEN mutations) at frequencies of 24,34%. Secondary glioblastomas develop in younger patients (mean, 45 years) and frequently show TP53 mutations (65%) and LOH 10q (63%). Common to both primary and secondary glioblastoma is LOH on 10q, distal to the PTEN locus; a putative suppressor gene at 10q25-qter may be responsible for the glioblastoma phenotype. Of the TP53 point mutations in secondary glioblastomas, 57% were located in hotspot codons 248 and 273, while in primary glioblastomas, mutations were more widely distributed. Furthermore, G:C,A:T mutations at CpG sites were more frequent in secondary than in primary glioblastomas (56% vs 30%). These data suggest that the TP53 mutations in these glioblastoma subtypes arise through different mechanisms. There is evidence that G:C,A:T transition mutations at CpG sites in the TP53 gene are significantly more frequent in low-grade astrocytomas with promoter methylation of the O6 -methylguanine-DNA methyltransferase (MGMT) gene than in those without methylation. This suggests that, in addition to deamination of 5-methylcytosine (the best known mechanism of formation of, G:C,A:T, transitions, at, CpG, sites),, involvement of alkylating agents that produce O6 -methylguanine or related adducts recognized by MGMT cannot be excluded in the pathway leading to secondary glioblastomas. [source] Plastic bronchitis caused by neoplastic infiltrates in a childPEDIATRIC PULMONOLOGY, Issue 9 2006Tamar Kuperman MD Abstract We report on a case of a 7-year-old girl admitted for pneumonia not responding to oral antibiotics. During hospitalization, her pulmonary status deteriorated as a result of significant atelectasis. An extensive workup revealed an anaplastic large-cell lymphoma with neoplastic cells, found in both a biopsied lymph node and pleural fluid aspirate. Bronchoscopic examination showed nearly complete obstruction of the left side by bronchial casts composed of tumor cells, fibrin, and necrotic material, consistent with plastic bronchitis. Neoplastic infiltration of the bronchi should be considered in the differential diagnosis of disease entities causing plastic bronchitis in children. Pediatr Pulmonol. © 2006 Wiley-Liss, Inc. [source] Non-Hodgkin disease in ,-thalassemia majorAMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2006Zaher K. Otrock Abstract Thalassemia is a spectrum of diseases characterized by the decrease or absence of globin chains. The occurrence of lymphoma in thalassemia has rarely been reported, and our review of the English literature revealed only four cases. Because anemia is always masked by regular transfusions in thalassemic patients, physicians discover a hidden malignancy late in the course of the disease. We hereby report the case of a thalassemic patient developing non-Hodgkin disease and discuss the possibility of a link between the two disease entities. This case is intended to alert physicians of the possibility of a malignancy in thalassemia patients. Am. J. Hematol. 81:62,64, 2006. © 2005 Wiley-Liss, Inc. [source] The Tyranny of Diagnosis: Specific Entities and Individual ExperienceTHE MILBANK QUARTERLY, Issue 2 2002Charles E. Rosenberg Diagnosis has always played a pivotal role in medical practice, but in the past two centuries, that role has been reconfigured and has become more central as medicine,like Western society in general,has become increasingly technical, specialized, and bureaucratized. Disease explanations and clinical practices have incorporated, paralleled, and, in some measure, constituted these larger structural changes. This modern history of diagnosis is inextricably related to disease specificity, to the notion that diseases can and should be thought of as entities existing outside the unique manifestations of illness in particular men and women. During the past century especially, diagnosis, prognosis, and treatment have been linked ever more tightly to specific, agreed-upon disease categories, in both concept and everyday practice. In fact, this essay might have been entitled "Diagnosis Mediates an Invisible Revolution: The Social and Intellectual Significance of Specific Disease Concepts." It would have been even more precise, if rather less arresting. The articulation and acceptance of specific disease entities constitute one of the most important intellectual and cultural events of the past two centuries. This notion is central to how we organize health care delivery, think about ourselves, debate and formulate social policy, and define and manage deviance. Diagnosis is indispensable to linking specific disease concepts with doctor and patient and the social and economic institutions shaping such clinical interactions. Disease is a social entity, not an array of ideal types. The history of medicine is partly the story of how disease entities have become social entities, accumulating the flesh of diagnostic and therapeutic practice, social expectation, and bureaucratic reification. Despite criticism of reductionist medicine in the West and less focus on disease entities and mechanisms, our social response still depends on this concept of sickness. But this concept can no longer remain invisible if we are to understand contemporary medicine as both a social and a technological system. The articulation and acceptance of specific disease entities constitute one of the most important intellectual and cultural events of the past two centuries. This notion is central to how we organize health care delivery, think about ourselves, debate and formulate social policy, and define and manage deviance. Diagnosis is indispensable to linking specific disease concepts with doctor and patient and the social and economic institutions shaping such clinical interactions. Disease is a social entity, not an array of ideal types. The history of medicine is partly the story of how disease entities have become social entities, accumulating the flesh of diagnostic and therapeutic practice, social expectation, and bureaucratic reification. Despite criticism of reductionist medicine in the West and less focus on disease entities and mechanisms, our social response still depends on this concept of sickness. But this concept can no longer remain invisible if we are to understand contemporary medicine as both a social and a technological system. The articulation and acceptance of specific disease entities constitute one of the most important intellectual and cultural events of the past two centuries. This notion is central to how we organize health care delivery, think about ourselves, debate and formulate social policy, and define and manage deviance. Diagnosis is indispensable to linking specific disease concepts with doctor and patient and the social and economic institutions shaping such clinical interactions. Disease is a social entity, not an array of ideal types. The history of medicine is partly the story of how disease entities have become social entities, accumulating the flesh of diagnostic and therapeutic practice, social expectation, and bureaucratic reification. Despite criticism of reductionist medicine in the West and less focus on disease entities and mechanisms, our social response still depends on this concept of sickness. But this concept can no longer remain invisible if we are to understand contemporary medicine as both a social and a technological system. The articulation and acceptance of specific disease entities constitute one of the most important intellectual and cultural events of the past two centuries. This notion is central to how we organize health care delivery, think about ourselves, debate and formulate social policy, and define and manage deviance. Diagnosis is indispensable to linking specific disease concepts with doctor and patient and the social and economic institutions shaping such clinical interactions. Disease is a social entity, not an array of ideal types. The history of medicine is partly the story of how disease entities have become social entities, accumulating the flesh of diagnostic and therapeutic practice, social expectation, and bureaucratic reification. Despite criticism of reductionist medicine in the West and less focus on disease entities and mechanisms, our social response still depends on this concept of sickness. But this concept can no longer remain invisible if we are to understand contemporary medicine as both a social and a technological system. [source] The Elephant in the Room: Failings of Current Clinical Endpoints in Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010J. D. Schold In this opinion piece, we address the limitations of the two most common clinical endpoints in kidney transplantation trials (acute rejection and renal function) and attempt to offer a reasonable framework by which to find true and reliable early endpoints that reflect long-term outcomes. Other potential endpoints tested in recent years, including the use of genomic and proteomic markers are still in development. Until other reliable endpoints are established, it is important to understand what can be inferred from ongoing studies that utilize these endpoints and what further information we need to derive ,true' surrogate endpoints. We consider evaluation of current markers using the ,Prentice criteria', which bases assessment of endpoints as true surrogates on four primary rules. Based on our assessment, progress in understanding the safety and efficacy of new therapies and interventions in kidney transplantation will remain limited with current makers. Prospectively, we advocate: (i) significant caution in extrapolating long-term outcomes from currently utilized clinical markers, (ii) use of traditional hard endpoints whenever feasible and (iii) dedication of efforts for more data collection on specific disease entities and greater diligence in determining the onset of deleterious processes. [source] Upregulation of TNF Receptor Type 2 in Human and Experimental Renal Allograft RejectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2009U. Hoffmann An important role of TNF interacting with TNFR2 has been shown in different models of ischemic, nephrotoxic and immune-mediated renal injury. To systematically evaluate the expression of TNFR2 in renal allograft rejection, we investigated human renal allograft biopsies and, in addition, established an experimental transplantation model in rats to verify the human data under standardized conditions. The expression of TNFR2 was analyzed in 96 human renal allograft biopsies with different disease entities. In a 6-day and a 28-day experimental protocol, TNFR2 was examined in kidney specimens and in the urine of control, uni-nephrectomized and transplanted rats ± cyclosporine treatment (n = 114). In human biopsies and in rat allografts on day 6 with acute allograft rejection, significantly elevated expression of TNFR2 was observed in tubular epithelial cells, podocytes, B cells and monocytes/macrophages. The expression level was associated with renal function. The TNFR2 expression level at day 28 was significantly lower compared to day 6. TNFR2 is markedly upregulated both in human and experimental acute renal allograft rejection. Our data are robust and consistent between different species, suggesting a role for TNFR2 in the early course of rejection. [source] HLA polymorphisms in African Americans with idiopathic inflammatory myopathy: Allelic profiles distinguish patients with different clinical phenotypes and myositis autoantibodiesARTHRITIS & RHEUMATISM, Issue 11 2006Terrance P. O'Hanlon Objective To investigate possible associations of HLA polymorphisms with idiopathic inflammatory myopathy (IIM) in African Americans, and to compare this with HLA associations in European American IIM patients with IIM. Methods Molecular genetic analyses of HLA,A, B, Cw, DRB1, and DQA1 polymorphisms were performed in a large population of African American patients with IIM (n = 262) in whom the major clinical and autoantibody subgroups were represented. These data were compared with similar information previously obtained from European American patients with IIM (n = 571). Results In contrast to European American patients with IIM, African American patients with IIM, in particular those with polymyositis, had no strong disease associations with HLA alleles of the 8.1 ancestral haplotype; however, African Americans with dermatomyositis or with anti,Jo-1 autoantibodies shared the risk factor HLA,DRB1*0301 with European Americans. We detected novel HLA risk factors in African American patients with myositis overlap (DRB1*08) and in African American patients producing anti,signal recognition particle (DQA1*0102) and anti,Mi-2 autoantibodies (DRB1*0302). DRB1*0302 and the European American,, anti,Mi-2,associated risk factor DRB1*0701 were found to share a 4,amino-acid sequence motif, which was predicted by comparative homology analyses to have identical 3-dimensional orientations within the peptide-binding groove. Conclusion These data demonstrate that North American IIM patients from different ethnic groups have both shared and distinct immunogenetic susceptibility factors, depending on the clinical phenotype. These findings, obtained from the largest cohort of North American minority patients with IIM studied to date, add additional support to the hypothesis that the myositis syndromes comprise multiple, distinct disease entities, perhaps arising from divergent pathogenic mechanisms and/or different gene,environment interactions. [source] The new World Health Organization classification of haematopoietic and lymphoid tumours: a dermatopathological perspectiveBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2002D.N. Slater Summary The World Health Organization (WHO) has published a new consensus classification of tumours of haematopoietic and lymphoid tissue, based on recognizable disease entities defined by clinical and scientific criteria. The WHO does not support the use of stand-alone organ-related classifications, such as for skin. The Royal College of Pathologists (London) has adopted the WHO classification in its minimum dataset for the histopathological reporting of lymphoma and this will be used in the National Health Service Skin Cancer Dataset. The purpose of this review is to highlight the principal primary and secondary cutaneous haematopoietic and lymphoid tumours that are defined in the WHO classification. The review also discusses selected problematical areas in the WHO classification relevant to the skin and contains suggestions to encourage a unified approach in the use of the WHO coded summary. These represent an attempt to facilitate future progress and research in the field of cutaneous lymphoma. They are perceived as possible building-blocks for wider discussion and not as alterations to the classification. The WHO classification has been compared with a road map that indicates directions for future clinical and scientific research. [source] Occurrence of dysregulated oncogenes in primary plasma cells representing consecutive stages of myeloma pathogenesis: indications for different disease entitiesBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2003Thomas Rasmussen Summary. This study investigated the expression pattern in primary plasma cells (PCs) of putative oncogenes suggested to be involved in multiple myeloma (MM) development. cDNA archives were generated by global reverse transcription polymerase chain reaction from CD38++/CD19,/CD56,/++ aberrant PCs of a prospective cohort of 96 subjects, including healthy individuals, patients with monoclonal gammopathies of undetermined significance (MGUS), MM and MM with extramedullary manifestations (ExMM). The cDNA archives were analysed quantitatively for expression of the cyclin D1, fibroblast growth factor receptor 3 (FGFR3), C-MYC, C-MAF and cyclin D3 oncogenes. In addition, all patients were screened for IGH,MMSET hybrid transcripts. None of the analysed oncogenes was randomly distributed. C-MYC and cyclin D3 expression increased at the extramedullary transformation stage. Furthermore, C-MYC and cyclin D3 expression in CD56+ MM was similar to MGUS, whereas CD56, MM was similar to ExMM. FGFR3/IGH,MMSET was only observed among CD56+ MM patients, whereas an increased frequency of C-MAF dysregulation was seen among CD56, MM. High cyclin D1 expression levels were identified at similar frequencies at all stages, whereas the frequency of patients with low cyclin D1 levels increased during MM development. These data support the stepwise transformation model accumulating genetic alterations and proliferative capacity during MM initiation and development resulting in different clinical entities. [source] Clinical aspects of neuromuscular transmission disordersACTA NEUROLOGICA SCANDINAVICA, Issue 2006Amelia Evoli Autoimmune disorders of neuromuscular transmission are caused by antibodies (abs) directed against membrane proteins at the motor end-plate. Myasthenia gravis (MG) is due, in most cases, to abs against the nicotinic acetylcholine receptor (AChR). Anti-AChR-positive MG actually includes different disease entities: weakness can be confined to extrinsic ocular muscles or can be generalized; patients with generalized MG (G-MG) can be subdivided on the basis of age of onset, HLA association and thymic pathology. About 15% of G-MG patients are anti-AChR-negative; in a proportion of these cases serum abs against the muscle- specific kinase (MuSK) are found. Anti-MuSK-positive MG is characterized by predominant involvement of bulbar muscles and very low frequency of thymic pathology. The Lambert-Eaton myasthenic syndrome (LEMS) is caused by abs against voltage-gated calcium channels at nerve terminal. LEMS is characterized by muscle weakness and autonomic disturbances and it is paraneoplastic in over 50% of the cases. In neuromyotonia and cramp-fasciculation syndrome, that are thought to be due to anti-voltage-gated potassium channel abs, signs of peripheral nerve hyperexcitability can be associated with CNS features. [source] Diversity of genome profiles in malignant lymphomaCANCER SCIENCE, Issue 3 2010Masao Seto (Cancer Sci 2010; 101: 573,578) Characteristic chromosome translocations are associated with specific disease entities, and are known to play a pivotal role in lymphoma development. Chromosome translocation alone, however, is not sufficient to produce tumors. Factors including the microenvironment and epigenetic and genetic alterations other than chromosome translocations have been shown to play a role in lymphoma development. Follicular lymphoma cells proliferate in close contact with follicular dendritic cells. Mucosa-associated lymphoid tissue (MALT) lymphoma cells proliferate at the marginal zone area of reactive follicles which are formed by preceding chronic inflammation. The importance of genetic alterations other than chromosome translocation has been recognized since the introduction of array comparative genomic hybridization (array CGH). Variations in the genomic profile among patients with the same disease entity have been found by array CGH analyses. These variations indicate that multiple genetic pathways leading to the development of lymphomas may exist and hence result in the variable clinicopathological features observed. [source] Genetic alterations and signaling pathways in the evolution of gliomasCANCER SCIENCE, Issue 12 2009Hiroko Ohgaki Gliomas are the most common primary brain tumors. They account for more than 70% of all neoplasms of the central nervous system and vary considerably in morphology, location, genetic alterations, and response to therapy. Most frequent and malignant are glioblastomas. The vast majority (>90%) develops rapidly after a short clinical history and without evidence of a less malignant precursor lesion (primary or de novo glioblastoma). Secondary glioblastomas develop more slowly through progression from low-grade or anaplastic astrocytoma. These glioblastoma subtypes constitute distinct disease entities that affect patients of different age, develop through distinct genetic pathways, show different RNA and protein expression profiles, and may differ in their response to radio- and chemotherapy. Recently, isocitrate dehydrogenase 1 (IDH1) mutations have been identified as a very early and frequent genetic alteration in the pathway to secondary glioblastomas as well as that in oligodendroglial tumors, providing the first evidence that low-grade astrocytomas and oligodendrogliomas may share common cells of origin. In contrast, primary glioblastomas very rarely contain IDH1 mutations, suggesting that primary and secondary glioblastomas may originate from different progenitor cells, despite the fact that they are histologically largely indistinguishable. In this review, we summarize the current status of genetic alterations and signaling pathways operative in the evolution of astrocytic and oligodendroglial tumors. (Cancer Sci 2009; 100 2235,2241) [source] The analysis of fundus autofluorescence patterns in retinal diseasesACTA OPHTHALMOLOGICA, Issue 2007P POPOVIC Purpose: Fundus autofluorescence (AF) imaging is a method that shows accumulation of lipofuscin in the retinal pigment epithelium cells in vivo. Fundus AF may be recorded in retinal diseases either by scanning laser ophthalmoscope or by fundus camera using the appropriate filter. The aim of this study was to analyze the AF pattern by both methods. Methods: 20 patients with different retinal diseases including retinitis pigmentosa, cone-rod dystrophy, Stargardt disease, Best macular dystrophy, central serous retinopathy and age-related macular degeneration were included in the study. AF images were obtained from each subject using a confocal scanning laser ophthalmosope and digital fundus camera. The distribution and amount of AF were compared by the use of both systems. Results: In all disease entities both instruments showed distinct pattern of AF typical for the disease. Areas of high intensity of AF recorded with HRA matched to areas of increased intensity of AF detected with fundus camera. The distribution of areas of low or absent AF also corresponded well in both systems. Images taken with conventional fundus camera were in general lower contrasted and therefore less sharp. This was particularly true for patients with even mild media opacity. The advantage of fundus camera was however a recording of AF of a greater field of view. Conclusions: AF imaging is a very useful noninvasive method for detecting RPE abnormalities. In clinical practice, when scanning laser ophthalmoscope for recording of AF is not available, conventional digital fundus camera can be used for screening of patients suspected to have retinal disease. Care should be taken in patients with nuclear cataract, as the AF image is influenced by the AF of the crystalline lens by a great amount. [source] Treatment of choroidal neovascularization using intravitreal bevacizumabACTA OPHTHALMOLOGICA, Issue 5 2007Robert Pedersen Abstract. Purpose:, This study aimed to assess the pharmacodynamic profile of intravitreal bevacizumab in relation to best corrected visual acuity (BCVA), foveal thickness, and other aspects of macular morphology after intravitreal injection of bevacizumab in eyes with subretinal choroidal neovascularization (CNV). Methods:, A retrospective observational, uncontrolled case series including 26 eyes in 25 patients followed for up to 6 months after intravitreal injection of bevacizumab 1 mg repeated as deemed necessary after monthly assessments by biomicroscopy, optical coherence tomography, colour fundus photography, fluorescein angiography and BCVA determination. At follow-up, cases were classified by morphological treatment response (reduction or elimination of pathological neovascular leakage, retinal thickening or serous retinal detachment) or absence of response (deterioration or lack of improvement). Primary disease entities included age-related macular degeneration (22 eyes, four of which had evidence of retinal angiomatous proliferation), idiopathic peripapillary neovascularization (one eye), and angioid streaks (three eyes in two patients). Results:, One month after the first injection, apparent morphological improvement was observed in 24/26 eyes and mean BCVA had improved by 3.1 ± 7.8 letters (p = 0.05). Of these 24 responders, which included all primary diagnoses, 11 (46%) demonstrated BCVA improvement of ,,5 letters. The two non-responders (7.7%) had lost >,3 lines of vision at 2 months follow-up. Overall, 18 eyes completed 6 months follow-up, with a mean BCVA improvement of 0.5 ± 12.7 letters, and 22 eyes completed 3 months follow-up, with a mean BCVA improvement of 2.0 ± 11.0 letters. Two months after the first injection, 11 (46%) of the 24 responders demonstrated signs of recurrent CNV activity, defined as decreased BCVA and/or increased retinal thickness and/or fluorescein angiographic CNV leakage. No serious drug-related adverse events were observed during the course of the study. Conclusions:, Overall mean BCVA remained stable throughout the study. Morphological signs of reduced CNV activity were seen in the majority of eyes at 2,4 weeks after intravitreal bevacizumab injection. Half the responders showed signs of renewed CNV activity at 2 months after their first injection. All first-injection responders were also second-injection responders. [source] Update on epidemiology of pollinosis in Japan: changes over the last 10 yearsCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 1 2010K. Nakae Summary A nationwide epidemiologic survey of atopic diseases including allergic pollinosis was conducted in 9656 Japanese otorhinolaryngologists and their family members during the Japanese cedar pollen dispersion season in 2008 using methods identical to a previous survey that was performed in 1998. The survey response rate was 37.7% (compared with 42.8% in 1998). The overall prevalence rate of Japanese cedar pollinosis was 26.5%, which is an increase of approximately 9% from that noted in 1998. Similar increases were observed in all age groups, and the prevalence rate was similar between male and female respondents. A unimodal distribution was observed in male and female subjects, with a peak in both men and women aged in their 40s. Nationwide, a consistent positive relation was observed between the prevalence of Japanese cedar pollinosis and the regional Japanese cedar pollen counts. The prevalence rate of pollinosis other than Japanese cedar pollinosis and of perennial allergic rhinitis was 15.4% and 23.3%, respectively; both disease entities tended to occur more frequently in male than in female subjects. The prevalence rate of asthma, atopic dermatitis, and food allergy was 5.2%, 14.1%, and 3.9%, respectively. Our results suggest that the prevalence rates of atopic diseases including Japanese cedar pollinosis are dramatically increasing across all age groups in Japan. In particular, the increasing prevalence rate of Japanese cedar pollinosis seems to reflect higher exposure to the Japanese cedar pollen antigen in many prefectures. [source] The brachydactylies: a molecular disease familyCLINICAL GENETICS, Issue 2 2009S Mundlos Brachydactyly refers to shortening of the hands and/or feet due to missing, deformed, or shortened bones. It may occur as an isolated trait or as part of a syndrome. According to their pattern of skeletal involvement, the isolated brachydactyly forms have been categorized in the groups A,D including several subgroups. As in many other genetic conditions, there is considerable phenotypic overlap between the groups. The identification of the molecular causes of these conditions has offered insights into their pathogenesis. The generation of animal models has facilitated research on the pathogenic events during digit development that lead to the brachydactyly phenotype. These studies have shown that the BMP pathway plays a pivotal role in the normal development of digits and joints and that the majority of brachydactyly disease genes are directly or indirectly linked to this pathway. Together, these genes function in a regulatory network which is deregulated in the disease state. As a consequence of the close interactions within the network, overlapping phenotypes are generated that are, nevertheless, characterized by specific recognizable patterns. This principle does not only apply for the brachydactylies but is also valid for many other disease entities. Groups of diseases that show a common phenotypic pattern due to the deregulation of a molecular network are suggested to be called molecular disease families. [source] Tight junctions, leaky intestines, and pediatric diseasesACTA PAEDIATRICA, Issue 4 2005Z Liu Abstract Background: Tight junctions (TJs) represent the major barrier within the paracellular pathway between intestinal epithelial cells. Disruption of TJs leads to intestinal hyperpermeability (the so-called "leaky gut") and is implicated in the pathogenesis of several acute and chronic pediatric disease entities that are likely to have their origin during infancy. Aim: This review provides an overview of evidence for the role of TJ breakdown in diseases such as systemic inflammatory response syndrome (SIRS), inflammatory bowel disease, type 1 diabetes, allergies, asthma, and autism. Conclusion: A better basic understanding of this structure might lead to prevention or treatment of these diseases using nutritional or other means. [source] Evaluation of Cardiac Involvement in Hypereosinophilic Syndrome: Complementary Roles of Transthoracic, Transesophageal, and Contrast EchocardiographyECHOCARDIOGRAPHY, Issue 8 2006Rajesh Shah M.D. Hypereosinophilic syndrome is a rare but important systemic disease with multiple clinical presentations. Approximately 40% of these cases have cardiac involvement. Echocardiography is the most easily available and versatile imaging modality in assessing cardiac involvement in this disease process. As described and reviewed in this case, it may be the first imaging modality to raise suspicion of this disease entity. Hence, clinicians interpreting echocardiograms and caring for patients need to be aware of the manifestations and complementary roles of various echo techniques in delineating cardiac involvement. Furthermore, the importance of a thorough history and laboratory review prior to echocardiography may provide valuable clues which may otherwise be missed. [source] | |||||||||||||||||||||||||||||||||||||