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Fibrosing Disorder (fibrosing + disorder)
Selected AbstractsHypercalcemia and Overexpression of CYP27B1 in a Patient With Nephrogenic Systemic Fibrosis: Clinical Vignette and Literature Review,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2009Vivian Y Pao Abstract Nephrogenic systemic fibrosis (NSF) is a disease of thickened, hard, hyperpigmented skin lesions with or without systemic fibrosis occurring in patients with renal insufficiency and associated with the administration of gadolinium-containing contrast. The pathogenesis of this disease is unclear, and there is no definitive treatment. We describe a 71-yr-old patient with stable chronic lymphocytic leukemia (CLL), end-stage renal disease (ESRD), and NSF who presented with hypercalcemia in 2006. Before onset of renal insufficiency in 2002, serum calcium, phosphorus, and PTH levels were normal. In 2004, the patient began hemodialysis, and he was diagnosed with NSF in 2005, shortly after undergoing an MRI with gadolinium contrast administration. Over the next 6 mo, albumin-corrected serum total calcium levels rose from 9.9 to 13.1 mg/dl (normal range, 8.5,10.5 mg/dl) with normal serum phosphorus levels. On admission in September 2006, 1,25-dihydroxyvitamin D [1,25(OH)2D] levels were elevated at 130.7 pg/ml (normal range, 25.1,66.1 pg/ml). Biopsy of an NSF lesion showed increased 25-hydroxyvitamin D3,1-, hydroxylase (CYP27B1) immunostaining compared with the biopsy from a normal control. This is the first reported association of NSF with hypercalcemia caused by elevated 1,25(OH)2D levels. This metabolic disturbance should be sought in future cases to determine a connection between NSF, 1,25(OH)2D metabolism, and CYP27B1 activation in the skin, which may shed light on the pathogenesis of this unusual local and systemic fibrosing disorder. [source] Gadolinium-Induced Nephrogenic Systemic Fibrosis Is Associated with Insoluble Gd Deposits in Tissues: In Vivo Transmetallation Confirmed by MicroanalysisJOURNAL OF CUTANEOUS PATHOLOGY, Issue 12 2009Charu Thakral Background: Nephrogenic systemic fibrosis (NSF) is an extremely debilitating systemic fibrosing disorder affecting renal failure patients. The association of NSF with gadolinium (Gd) containing magnetic resonance contrast agents was noted in 2006. Gd deposition in skin biopsies was demonstrated shortly thereafter. Methods: We used automated scanning electron microscopy (SEM)/energy dispersive x-ray spectroscopy for in situ quantitative analysis of insoluble Gd-containing deposits, recording multi-elemental composition and spatial distribution of detected features. Results: Gd was detected in all 29 patients (53 of 57 skin biopsies) with NSF, biopsied from 2 weeks to 3 years after Gd exposure. Gd concentration ranged from 1 to 2270 cps/mm2 and was detected predominantly in the deep dermis and subcutaneous fibrous septa. Gd was found associated with Ca, P and sometimes Fe or Zn. Patients with sequential biopsies showed persistence or increase of Gd in tissues (6 of 11). Transmission electron microscopy (TEM) identified the intracellular deposits in fibrocytes and macrophages. Conclusions: The demonstration of insoluble tissue deposits of Gd with co-associated elements clearly confirms in vivo transmetallation and dissociation of soluble Gd-chelates. Toxic Gd3+ may trigger fibrosis under permissive conditions, e.g., in renal insufficiency. Pathologists and clinicians need to be aware of this serious but preventable disease. [source] Nephrogenic Systemic Fibrosis Among Liver Transplant Recipients: A Single Institution Experience and Topic UpdateAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2006M. Maloo Nephrogenic systemic fibrosis (NSF) is a recently characterized systemic fibrosing disorder developing in the setting of renal insufficiency. NSF's rapidly progressive nature resulting in disability within weeks of onset makes early diagnosis important. Two reports of NSF after liver transplantation are known of. We present three cases of NSF developing within a few months after liver transplantation and review the current literature. Loss of regulatory control of the circulating fibrocyte, its aberrant recruitment, in a milieu of renal failure and a recent vascular procedure appear important in its development. Known current therapies lack consistent efficacy. Only an improvement in renal function has the greatest likelihood of NSF's resolution. Delayed recognition may pose a significant barrier to functional recovery in the ubiquitously deconditioned liver transplant patient. Early recognition and implementation of aggressive physical therapy appear to have the greatest impact on halting its progression. [source] Induction of the expression of profibrotic cytokines and growth factors in normal human peripheral blood monocytes by gadolinium contrast agentsARTHRITIS & RHEUMATISM, Issue 5 2009Peter J. Wermuth Objective Nephrogenic systemic fibrosis (NSF) is a severe fibrosing disorder occurring in patients with renal insufficiency. The majority of patients with this disorder have documented exposure to magnetic resonance imaging contrast agents containing Gd. The purpose of this study was to examine the effects of gadolinium diethylenetriaminepentaacetic acid bismethylamide (Gd[DTPA-BMA]; Omniscan) as compared with Gd-DTPA and GdCl3 on the expression and production of cytokines and growth factors by normal human peripheral blood monocytes in vitro and to examine whether conditioned media from Gd-exposed peripheral blood monocytes could induce a profibrotic phenotype in dermal fibroblasts. Methods Normal human peripheral blood monocytes isolated by Ficoll-Hypaque gradient centrifugation and plastic adherence were incubated with various concentrations of Gd[DTPA-BMA], Gd-DTPA, or GdCl3. Gene expression of interleukins 4, 6, and 13, interferon-,, tumor necrosis factor ,, transforming growth factor ,, connective tissue growth factor, and vascular endothelial growth factor were assessed by real-time polymerase chain reaction (PCR) analysis. Production and secretion of cytokines and growth factors by Gd compound,exposed monocytes was quantified by enzyme-linked immunosorbent assay proteome multiplex arrays. The effects of conditioned media from the Gd compound,exposed monocytes on the phenotype of normal human dermal fibroblasts were examined by real-time PCR and Western blotting. Results The 3 Gd-containing compounds stimulated the expression and production of numerous cytokines and growth factors by normal human peripheral blood monocytes. Conditioned media from these cells induced a profibrotic phenotype in normal human dermal fibroblasts. Conclusion The 3 Gd-containing compounds studied induce potent cellular responses in normal human peripheral blood monocytes, which may participate in the development of tissue fibrosis in NSF. [source] Gadolinium-induced nephrogenic systemic fibrosis in a patient with an acute and transient kidney injuryBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2008R.E. Kalb Summary Nephrogenic systemic fibrosis (NSF) describes a characteristic fibrosing disorder which typically presents with indurated plaques on the trunk and extremities of patients with advanced renal disease. We present a case of biopsy-confirmed NSF in a patient with severe acute kidney injury with no prior history of renal disease. A 64-year-old man with an acute and severe decrease in glomerular filtration rate underwent magnetic resonance imaging studies with gadolinium contrast (OmniscanÔ) and subsequently developed NSF. His renal disease had normalized at the time his skin disease developed. Skin biopsies revealed findings of NSF and scanning electron microscopy with energy-dispersive X-ray spectroscopy confirmed insoluble gadolinium within lesional tissue. [source] Possible role of gadolinium in nephrogenic systemic fibrosis: report of two cases and review of the literatureCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 4 2007Y. L. Lim Summary Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy (NSF/NFD) is a rare fibrosing disorder that occurs in patients with renal failure. It is associated with significant mortality and morbidity. Patients typically present with painful or pruritic indurated plaques involving the limbs and trunk, with sparing of the face. Severity and rapidity of cutaneous progression correlate with poorer prognosis. To date, the management of NSF/NFD remains anecdotal. The aetiological link in NSF/NFD is also yet to be confirmed, but renal dysfunction seems a common feature. Following recent reports of a possible causative role of gadolinium, we present two patients with histologically confirmed NSF/NFD, who had exposure to gadolinium-containing contrast agents 1,2 months before onset of disease. Severity of renal impairment, lack of immediate dialysis after exposure and cumulative dose of gadolinium are possible factors influencing the development of NSF/NFD. The process of transmetallation of gadolinium chelates may occur in patients with renal impairment, leading to precipitation of free gadolinium in the dermis or other organs, causing tissue injury that ultimately leads to the clinical manifestations of NSF/NFD. Although the causative role is not proven, gadolinium-containing contrast agents should be used only if clearly necessary in patients with renal failure. [source] | ||||||||||