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Tissue Disorders (tissue + disorders)
Kinds of Tissue Disorders Selected AbstractsLung transplantation in patients with connective tissue disorders and esophageal dysmotilityDISEASES OF THE ESOPHAGUS, Issue 7 2008Warren J. Gasper SUMMARY., Lung and esophageal dysfunction are common in patients with connective tissue disease (CTD). Recent reports have suggested a link between pathologic gastroesophageal reflux and bronchiolitis obliterans syndrome (BOS) after lung transplant. Because patients with CTD have a high incidence of esophageal dysmotility and reflux, this group may be at increased risk of allograft dysfunction after lung transplantation. Little is known about antireflux surgery in these patients. Our aims were to describe: (i) the esophageal motility and reflux profile of patients with CTD referred for lung transplantation; and (ii) the safety and outcomes of laparoscopic fundoplication in this group. A retrospective review of 26 patients with CTD referred for lung transplantation between July 2003 and June 2007 at a single center. Esophageal studies included manometry and ambulatory 24-h pH monitoring. Twenty-three patients had esophageal manometry and ambulatory 24-h pH monitoring. Nineteen patients (83%) had pathologic distal reflux and 7 (30%) also had pathologic proximal reflux. Eighteen patients (78%) had impaired or absent peristalsis. Eleven of 26 patients underwent lung transplantation. Ten patients are alive at a median follow-up of 26 months (range 3,45) and one has bronchiolitis obliterans syndrome-1. Six patients had a laparoscopic fundoplication, 1 before transplantation and 5 after. All fundoplication patients are alive at median follow-up of 25 months (range 19,45). In conclusion, esophageal dysmotility and reflux are common in CTD patients referred for lung transplant. For this group, laparoscopic fundoplication is safe in experienced hands. [source] Mutation screening of the fibrillin-1 (FBN1) gene in 76 unrelated patients with Marfan syndrome or Marfanoid features leads to the identification of 11 novel and three previously reported mutations,,HUMAN MUTATION, Issue 5 2002Kathrin Rommel Abstract Mutations in the gene encoding fibrillin-1 (FBN1) cause Marfan syndrome (MFS) and other related connective tissue disorders. In this study we performed SSCP to analyze all 65 exons of the FBN1 gene in 76 patients presenting with classical MFS or related phenotypes. We report 7 missense mutations, 3 splice site alterations, one indel mutation, one nonsense mutation and two mutations causing frameshifts: a 16bp deletion and a single nucleotide insertion. 5 of the missense mutations (Y1101C, C1806Y, T1908I, G1919D, C2251R) occur in calcium-binding Epidermal Growth Factor-like (EGFcb) domains of exons 26, 43, 46 and 55, respectively. One missense mutation (V449I) substitutes a valine residue in the non-calcium-binding epidermal growth factor like domain (EGFncb) of exon 11. One missense mutation (G880S) affects the "hybrid" motif in exon 21 by replacing glycine to serine. The 3 splice site mutations detected are: IVS1,1G>A in intron 1, IVS38-1G>A in intron 38 and IVS46+5G>A in intron 46. C628delinsK was identified in exon 15 leading to the substitution of a conserved cysteine residue. Furthermore two frameshift mutations were found in exon 15 (1904-1919del ) and exon 63 (8025insC) leading to premature termination codons (PTCs) in exon 17 and 64 respectively. Finally we identified a nonsense mutation (R429X) located in the proline rich domain in exon 10 of the FBN1 gene. Y1101C, IVS46+5G>A and R429X have been reported before. © 2002 Wiley-Liss, Inc. [source] Prevention and treatment of systemic glucocorticoid side effectsINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2010Siamak Moghadam-Kia MD Background, Systemic glucocorticoids are used in dermatologic practice for various diseases including connective tissue disorders, bullous diseases, and many other dermatologic conditions. Patients with these diseases are at times treated with long-term courses of glucocorticoids, which place them at increased risk for glucocorticoid-induced side effects. Therefore, dermatologists must be knowledgeable of risks related to glucocorticoid use and be familiar with guidelines to manage them. Objective, To provide an update of recent advances in the prevention and treatment of major glucocorticoid-induced side effects. Methods, Review of the literature Results Data regarding the prevention and treatment of glucocorticoid-induced side effects are presented. Conclusion, This review should help dermatologists optimally manage and prevent glucocorticoid-induced side effects. [source] Role of the Latent Transforming Growth Factor ,,Binding Protein 1 in Fibrillin-Containing Microfibrils in Bone Cells In Vitro and In VivoJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2000Sarah L. Dallas Abstract Latent transforming growth factor ,,binding proteins (LTBPs) are extracellular matrix (ECM) proteins that bind latent transforming growth factor , (TGF-,) and influence its availability in bone and other connective tissues. LTBPs have homology with fibrillins and may have related functions as microfibrillar proteins. However, at present little is known about their structural arrangement in the ECM. By using antibodies against purified LTBP1, against a short peptide in LTBP1, and against epitope-tagged LTBP1 constructs, we have shown colocalization of LTBP1 and fibrillin 1 in microfibrillar structures in the ECM of cultured primary osteoblasts. Immunoelectron microscopy confirmed localization of LTBP1 to 10- to 12-nm microfibrils and suggested an ordered aggregation of LTBP1 into these structures. Early colocalization of LTBP1 with fibronectin suggested a role for fibronectin in the initial assembly of LTBP1 into the matrix; however, in more differentiated osteoblast cultures, LTBP1 and fibronectin 1 were found in distinct fibrillar networks. Overexpression of LTBP1 deletion constructs in osteoblast-like cells showed that N-terminal amino acids 67,467 were sufficient for incorporation into fibrillin-containing microfibrils and suggested that LTBP1 can be produced by cells distant from the site of fibril formation. In embryonic long bones in vivo, LTBP1 and fibrillin 1 colocalized at the surface of newly forming osteoid and bone. However, LTBP1-positive fibrils, which did not contain fibrillin 1, were present in cartilage matrix. These studies show that in addition to regulating TGF,1, LTBP1 may function as a structural component of connective tissue microfibrils. LTBP1 may therefore be a candidate gene for Marfan-related connective tissue disorders in which linkage to fibrillins has been excluded. [source] Localized Chronic Fibrosing Vasculitis or Localized Erythema Elevatum Diutinum?JOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005L. Clarke Localized chronic fibrosing vasculitis is a rare dermatosis that histologically resembles late-stage erythema elevatum diutinum (EED) but has a different clinical presentation. A 62-year-old male presented with bilateral nodules on his heels that first appeared two years ago and over the past six months had become extremely painful. He denied any recent trauma to the sites, and his medical history was significant only for diabetes mellitus, coronary artery disease, and osteoarthritis. Physical exam demonstrated focally ulcerated violet-red three-centimeter nodules on the medial aspects of both heels. Biopsy revealed dense concentric and lamellar fibrosis with foci of leukocytoclastic debris and a sparse infiltrate of histiocytes, neutrophils, eosinophils, and lymphocytes. No granulomas were present, and histochemical stains and tissue cultures for microorganisms were negative. Imaging studies showed no evidence of underlying osteomyelitis, cellulitis, or abscess formation. Laboratory studies demonstrated a markedly elevated IgA level that was shown to be polyclonal on serum immunofixation studies. All peripheral blood cell counts were normal. Thorough evaluations for systemic vasculitides and connective tissue disorders were negative. A diagnosis of localized chronic fibrosing vasculitis was made. This case illustrates the clinicopathologic overlap between this disorder and EED. [source] The de Quervain's screening tool: Validity and reliability of a measure to support clinical diagnosis and managementMUSCULOSKELETAL CARE, Issue 3 2008DipCOT, Rachel Batteson PhD Abstract Background:,Studies into the effectiveness of interventions for upper limb soft tissue disorders have been hampered by a lack of consistently used diagnostic criteria, meaning that comparison of research results is a problem. To aid homogeneous recruitment into a study of de Quervain's disease, a de Quervain's screening tool (DQST) was developed. This could also be used to facilitate clinical diagnosis and management in practice. Aims:,To provide evidence for the content and construct validity and test,retest and inter-rater reliability of the DQST. Method:,The study was conducted in an acute care, outpatient hand unit in a district general hospital. Three convenience samples of: 59 people with de Quervain's disease; 18 with carpal tunnel syndrome (CTS) and 16 with osteoarthritis (OA) of the carpometacarpal (CMC) joint were recruited. The DQST diagnostic criteria were initially generated from a literature review. Content validity was then established by expert doctors with an interest in upper limb musculoskeletal disorders (n = 7) rating the relevance of the seven items included. The DQST was then tested in people either already diagnosed with, or reported as having some of the symptoms of, de Quervain's disease. Construct validity was tested with people with CTS or OA of the CMC joint. Results:,The median DQST score was 5 (Interquartile range IQR = 4,6) out of a possible seven diagnostic criteria. Inter-rater reliability was excellent (Intra-class coefficient [ICC] = 0.85; 95% confidence interval [CI] = 0.75, 0.91). Test retest reliability was good (ICC = 0.64; 95% CI = 0.20, 0.87). Sensitivity (Se) and specificity (Sp) testing (Se = 1.00; Sp = 1.00) demonstrated that the DQST discriminated between people with de Quervain's disease, CTS or OA of the CMC joint. Conclusions:,The DQST is a valid, reliable tool which could be of assistance in aiding correct diagnosis for recruitment to clinical trials and in clinical practice. Future research is recommended to further examine retest reliability with a larger sample size and to identify the commonest diagnostic criteria required for inclusion. Copyright © 2008 John Wiley & Sons, Ltd. [source] Evaluation of 80 children with prolonged feverPEDIATRICS INTERNATIONAL, Issue 5 2003Ozgur Cogulu Abstract Background:,Several studies have been published regarding the etiology and evaluation of a child with prolonged fever, however, the reasons for the prolonged fever have changed during the years. The present study aims to determine the causes of prolonged fever, to investigate the relationship of fever using some basic laboratory tests, and to establish guidelines for the approach in those children. Methods:,The charts of 80 out of 17 490 hospitalized children who were seen between 1996 and 2001 with prolonged fever of longer than 2 weeks and unknown origin were reviewed in the university hospital of Izmir, Turkey. Their charts were evaluated in respect of age, sex, growth curves, educational level of their families, the duration and the magnitude of fever, causes of fever, and basic laboratory investigations such as white blood cell, blood smear, hemoglobin, erythrocyte sedimentation rate, and C-reactive protein. Results:,Forty-four (55.00%) were boys and 36 (45.00%) were girls. Forty-four children (55.00%) were aged between 1 month and 2 years, 21 (26.25%) were aged 3,6 years, seven (8.75%) were aged 7,10 years, and eight (10.00%) were older than 10 years. The mean age was 3.87 ± 4.17 years (range 3 months,17 years). Forty-six children (57.50%) had a prolonged fever that had lasted from 15,30 days, 18 (22.50%) from 31,60 days, and 16 (20.00%) had fever lasting more than 60 days. Final diagnosis had been reached in 70 of the 80 children (87.50%). The most common causes were infection (47/80), followed by immune deficiency (6/80), collagen tissue disorder (5/80), neoplasia (2/80), and miscellaneous (10/80) such as central fever in three, diabetes insipidus in two, familial Mediterranean fever in two, Kawasaki disease, foreign body in the respiratory system, and Crohn disease in one patient each. Among the laboratory tests white blood cell count, hemoglobin level and blood smear distribution of infection group were statistically significant. Conclusions:,The most common cause of fever of unknown origin remains infection. The proportion of collagen tissue disorders and neoplasia have been found to be decreased. Unusual reasons such as diabetes insipidus and foreign body in the respiratory system in the miscellaneous group have been detected. Age plays important role in the diagnosis of prolonged fever, while some basic laboratory tests might give clues in the evaluation and may suggest a diagnosis. [source] Neuromuscular involvement in various types of Ehlers,Danlos syndrome,ANNALS OF NEUROLOGY, Issue 6 2009Nicol C. Voermans MD Objective Ehlers,Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Muscle involvement is plausible based on recently discovered interactions between muscle cells and extracellular matrix molecules; however, muscle symptoms are only sporadically reported. We designed a cross-sectional study to find out whether neuromuscular features are part of EDS. Methods Standardized questionnaires, physical examination, nerve conduction studies, electromyography, muscle ultrasound, and muscle biopsy were performed in 40 EDS patients with the vascular, classic, tenascin-X (TNX),deficient type EDS, and hypermobility type of EDS caused by TNXB haploinsufficiency. Results Muscle weakness, myalgia, and easy fatigability were reported by the majority of patients. Mild-to-moderate muscle weakness (85%) and reduction of vibration sense (60%) were common. Nerve conduction studies demonstrated axonal polyneuropathy in five patients (13%). Needle electromyography myopathic features in nine patients (26%) and a mixed neurogenic-myopathic pattern in most (60%). Muscle ultrasound showed increased echo-intensity (48%) and atrophy (50%). Mild myopathic features were seen on muscle biopsy of five patients (28%). Overall, patients with the hypermobility type EDS caused by TNXB haploinsufficiency were least affected. Interpretation Mild-to-moderate neuromuscular involvement is common in various types of EDS, with a remarkable relation between residual TNX level and degree of neuromuscular involvement, compatible with a dose,effect relation. The findings of this study should increase awareness of neuromuscular symptoms in EDS patients and improve clinical care. They also point to a role of the extracellular matrix in muscle and peripheral nerve function. This is an updated version of this article that originally published online on June 29, 2009. Ann Neurol 2009;65:687,697 [source] STAT4 is a genetic risk factor for systemic sclerosis having additive effects with IRF5 on disease susceptibility and related pulmonary fibrosisARTHRITIS & RHEUMATISM, Issue 8 2009P. Dieudé Objective Systemic sclerosis (SSc) belongs to the group of connective tissue disorders (CTDs), among which are several disorders characterized by a type I interferon (IFN) signature. The recent identification of an association between IRF5 and SSc further highlights a key role for IFN. STAT4, which encodes STAT-4, contributes to IFN signaling, and its genetic variants were found to be associated with CTDs. The aim of this study was to determine whether the STAT4 rs7574865 single-nucleotide polymorphism is associated with SSc, and whether it interacts with IRF5. Methods Both the STAT4 rs7574865 and IRF5 rs2004640 polymorphisms were genotyped in 1,855 individuals of French Caucasian origin comprising a discovery set of 440 patients with SSc and 485 control subjects and a replication set of 445 patients with SSc and an additional 485 control subjects. Results STAT4 rs7574865 was shown to be associated with SSc (P = 0.001, odds ratio [OR] 1.29, 95% confidence interval [95% CI] 1.11,1.51). This association was not restricted to a particular phenotype. An additive effect of the STAT4 rs7574865 T allele and the IRF5 rs2004640 T allele was observed, resulting in a multiplicatively increased 1.28-fold risk of SSc. The OR for SSc was 2.72 (95% CI 1.86,3.99) for combinations of genotypes with ,3 risk alleles. An additive effect was also detected for fibrosing alveolitis: carriage of at least 3 risk alleles appeared to be an independent risk factor (P = 2.2 × 10,4, OR 1.97, 95% CI 1.28,3.04). Conclusion Our results establish STAT4 rs7574865 as a new SSc genetic susceptibility factor. STAT4 and IRF5 act with additive effects in terms of susceptibility to both SSc and SSc-related fibrosing alveolitis. [source] Perceived adverse drug reactions among non-institutionalized children and adolescents in GermanyBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2010Hildtraud Knopf WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Drug safety in paediatric medication is a public health concern. According to previous studies, the incidence of adverse drug reactions (ADRs) varies greatly from 0.7% to 2.7% among paediatric outpatients and from 2.6% to 18.1% among paediatric inpatients. Little has been reported on the risks of drug use in the general child population. WHAT THIS STUDY ADDS Our study showed that the prevalence of perceived ADRs in Germany was 0.9% among non-institutionalized children in general and 1.7% among children who had used at least one medicine within the 7 days before the medical interview. Perceived ADRs in the general child population were clustered with gastrointestinal disorders and subcutaneous tissue disorders. They appeared to be mild and at the lower limits of the range reported in other studies. Health surveys covering the use of a diverse range of drugs might be suitable for computing ADR prevalence and for identifying risk factors among non-institutionalized children. They should be taken into account together with other pharmacovigilance systems. AIMS Little has been reported on the risks of drug use in the general child population. This study investigated perceived adverse drug reactions (ADRs) among non-institutionalized children in Germany. METHODS All medicines used in the last 7 days before the medical interview were recorded among the 17 450 children aged 0,17 years who participated in the 2003,06 German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Perceived ADRs were reported by the children's parents and confirmed by trained medical professionals during the medical interview. RESULTS One hundred and fifty-seven medicines were involved in the occurrence of 198 perceived ADRs in 153 patients. This corresponded to 1.1% of total used drugs, 0.9% (95% confidence intervals 0.7, 1.1%) of all children, and 1.7% (1.4, 2.1%) of children treated with medications. About 40% of all perceived ADRs involved gastrointestinal disorders and 16% involved skin tissue disorders. Perceived ADRs were most frequently reported in relation to drugs acting on the nervous system (25.8%), followed by systemic anti-infectives (18.7%) and drugs acting on the respiratory system (16.2%). Risk factors for perceived ADRs included older age groups, polypharmacy (,2) and a poor health status. CONCLUSION Perceived ADRs in the general child population were clustered with gastrointestinal disorders and subcutaneous tissue disorders. They appeared to be mild and at the lower limits of the range reported in other studies. Health surveys covering the use of a diverse range of drugs might be suitable for computing ADR prevalence and identifying risk factors among non-institutionalized children. They should be taken into account together with other pharmacovigilance systems. [source] Toxicity of radiotherapy in patients with collagen vascular diseaseCANCER, Issue 3 2008Alexander Lin MD Abstract BACKGROUND. A diagnosis of collagen vascular disease (CVD) may predispose to radiotherapy (RT) toxicity. The objective of the current study was to identify factors that influence RT toxicity in the setting of CVD. METHODS. A total of 86 RT courses for 73 patients with CVD were delivered between 1985 and 2005. CVD subtypes include rheumatoid arthritis (RA; 33 patients), systemic lupus erythematosus (SLE; 13 patients), scleroderma (9 patients), dermatomyositis/polymyositis (5 patients), ankylosing spondylitis (4 patients), polymyalgia rheumatica/temporal arteritis (4 patients), Wegener granulomatosis (3 patients), and mixed connective tissue disorders (MCTD)/other (2 patients). Each patient with CVD was matched to 1 to 3 controls with respect to sex, race, site irradiated, RT dose (±2 Gray), and age (±5 years). RESULTS. There was no significant difference between CVD patients (65.1%) and controls (72.5%) experiencing any acute toxicity. CVD patients had a higher incidence of any late toxicity (29.1% vs 14%; P = .001), and a trend toward an increased rate of severe late toxicity (9.3% vs 3.7%; P = .079). RT delivered to the breast had increased risk of severe acute toxicity, whereas RT to the pelvis had increased risk of severe acute and late toxicity. RT administered in the setting of scleroderma carried a higher risk of severe late toxicity, whereas RT to SLE patients carried a higher risk of severe acute and late toxicity. CONCLUSIONS. Although generally well tolerated, RT in the setting of CVD appears to carry a higher risk of late toxicity. RT to the pelvis or in the setting of SLE or scleroderma may predispose to an even greater risk of severe toxicity. These issues should be considered when deciding whether to offer RT for these patients. Cancer 2008. © 2008 American Cancer Society. [source] Elastic fiber abnormalities in hypermobility type Ehlers,Danlos syndrome patients with tenascin-X mutationsCLINICAL GENETICS, Issue 4 2005MC Zweers Ehlers,Danlos syndrome (EDS) is a heterogeneous group of connective tissue disorders with characteristic skin and joint involvement. The concept that EDS is a disease of fibrillar collagen was challenged by the identification of a clinically distinct, recessive type of EDS caused by deficiency of the extracellular matrix protein tenascin-X (TNX). Interestingly, haploinsufficiency of TNX is associated with the dominantly inherited hypermobility type of EDS. In this study, we examined whether missense mutations in the TNX gene can account for some of the cases of hypermobility type EDS. Furthermore, we studied whether missense mutations or heterozygosity for truncating mutations in the TNX gene lead to alterations in the dermal connective tissue. Sequence analysis revealed three missense mutations in TNX in hypermobility type EDS patients, which were not present in 192 control alleles. Morphometric analysis of skin biopsies of these patients showed altered elastic fibers in one of them, suggesting that this missense mutation is disease causing. Light microscopic and ultrastructural changes of the elastic fibers were observed in TNX-haploinsufficient hypermobility type EDS patients, which were not found in hypermobility type EDS patients in whom TNX mutations were excluded. Our results indicate that the observed alterations in elastic fibers are specific for hypermobility type EDS patients with mutations of TNX. [source] | |||||||||||||